A 22-year-old man presented to a Canadian community hospital emergency department complaining of 2-3 weeks of abdominal pain and bloating associated with early satiety. He also noted weight loss of 20 pounds over the preceding months, leg and abdominal swelling with increased girth, and 1-2 loose, nonbloody stools per day.

Early satiety and bloating are nonspecific symptoms that can be due to gastroesophageal reflux disease, peptic ulcer disease, gastrointestinal obstruction, or gastroparesis. Weight loss in a young person, particularly if >5% of body weight, is concerning for a serious underlying medical issue. It could reflect reduced intake due to anorexia, odynophagia, or dysphagia or increased energy expenditure due to an inflammatory state such as infection or rheumatic disease. The etiology of the swelling needs to be elucidated. It may be due to increased hydrostatic forces as in heart failure, venous or lymphatic obstruction, or from lowered oncotic pressure resulting from hepatic disease, nephrotic syndrome, severe malnutrition (nonbloody loose stools), or a protein losing enteropathy.

The patient was transferred to a tertiary care center for closer access to specialty consultation. He described generalized abdominal pain increasing in intensity over three weeks; bilateral lower extremity, scrotal, abdominal wall, and sacral edema; and mild dyspnea on exertion. The early satiety was not associated with dysphagia, odynophagia, nausea, or vomiting. He denied fevers, chills, night sweats, nausea, vomiting, jaundice, easy bruising, orthopnea, paroxysmal nocturnal dyspnea (PND), or chest pain. His past medical history included asthma treated with fluticasone/salmeterol and albuterol. He was a Canadian of East Asian descent working as a plumber. He previously smoked three to four cigarettes per day for six years. He stopped smoking one month before presentation. He had one alcoholic beverage per week and smoked marijuana weekly. He denied any family history of similar symptoms or malignancy.The differential diagnosis for weight loss and anasarca is broad and includes malignancies, infectious diseases, rheumatic or inflammatory disorders, malabsorption, and advanced cardiac, renal, or liver disease. His history does not classically point in one direction. The mild dyspnea on exertion may be due to cardiac disease, but it is unlikely in the absence of orthopnea and PND. The dyspnea could be due to increased abdominal pressure if ascites are present, his underlying asthma, or another etiology such as anemia. Fevers, chills, and/or night sweats can be expected in infections and some malignancies, but their absence does not exclude infections and malignancies from the differential diagnoses. Particular attention should be paid to lymphadenopathy on the physical examination. The presence of an umbilical nodule (Sister Mary Joseph sign) could indicate a malignancy (gastrointestinal or lymphoma).

The differential diagnosis for weight loss and anasarca is broad and includes malignancies, infectious diseases, rheumatic or inflammatory disorders, malabsorption, and advanced cardiac, renal, or liver disease. His history does not classically point in one direction. The mild dyspnea on exertion may be due to cardiac disease, but it is unlikely in the absence of orthopnea and PND. The dyspnea could be due to increased abdominal pressure if ascites are present, his underlying asthma, or another etiology such as anemia. Fevers, chills, and/or night sweats can be expected in infections and some malignancies, but their absence does not exclude infections and malignancies from the differential diagnoses. Particular attention should be paid to lymphadenopathy on the physical examination. The presence of an umbilical nodule (Sister Mary Joseph sign) could indicate a malignancy (gastrointestinal or lymphoma).

On physical examination, his temperature was 38.1°C, heart rate was 138 beats per minute, blood pressure was 123/86 mm Hg, respiratory rate was 20 breaths per minute, and oxygen saturation was 97% on room air. He appeared uncomfortable and diaphoretic. No scleral icterus or jaundice was appreciated. There were no palpable cervical, axillary, or inguinal lymph nodes. Cardiac examination revealed tachycardia and no murmurs, rubs, gallops, or jugular venous distention. Abdominal examination revealed abdominal distention, diffuse tenderness to deep palpation, bulging flanks, and a positive fluid wave. Liver and spleen could not be palpated or percussed secondary to abdominal distention. He had pitting bilateral lower extremity edema that extended to and included the scrotum. Neurologic and pulmonary examinations were unremarkable.

His examination reveals low-grade fever, tachycardia, and diaphoresis. Whether this represents progression of his primary disease or he has acutely developed a superimposed infection is uncertain at this point. He has notable anasarca but no jugular venous distention, crackles, or S3 gallop. The lack of evidence of pulmonary edema or increased central venous pressure on physical examination increases the likelihood of cirrhosis, hypoalbuminemia, or obstruction (lymphatic or venous) and decreases the likelihood of heart failure as the etiology of his peripheral edema and likely ascites. Despite the prominence of gastrointestinal symptoms, he has neither jaundice nor stigmata of chronic liver disease. Periorbital edema, which may be present in nephrotic syndrome, is also absent. Although he has no palpable peripheral lymphadenopathy, malignancy remains a concern.

Testing should include urinalysis for proteinuria and coagulation studies to assess synthetic function of the liver. Abdominal ultrasound is indicated to confirm ascites. If present, a diagnostic paracentesis should be performed to rule out spontaneous bacterial peritonitis and determine whether the ascites is from portal hypertension, hypoalbuminemia, or peritoneal disease. If the transaminases are elevated or if the ascitic fluid is concerning for malignancy, he will need a computed tomography (CT) of the abdomen and pelvis. A protein losing enteropathy due to malignancies (gastric cancer or lymphoma), rheumatic disease (systemic lupus erythematosus [SLE]), or infiltrative disease (amyloid) is also a possibility. If the other studies are unrevealing, stool should be sent for alpha-1 antitrypsin.

Laboratory studies revealed hemoglobin 7.8 g/dL, platelets 53 k/mm³, white blood cell count (WBC) 10.6 k/mm³, alkaline phosphatase (ALP) 217 U/L, albumin 2.7 g/dL, reticulocyte count 3 k/mm³ (reference range, 30-110 k/mm³), and ferritin 1,310 ng/mL (reference range, 20-400 ng/L). Serum aminotransferase levels, bilirubin, coagulation panel, electrolytes, and creatinine were normal. Urinalysis was negative for blood, leukocytes, and protein. Diagnostic paracentesis demonstrated a serum-ascites-albumin gradient (SAAG) of two and macrophage predominance (WBC 250 U/L). Ascitic fluid cytology and culture were negative. Blood cultures, human immunodeficiency virus (HIV)-1 and 2, cytomegalovirus (CMV), and Epstein–Barr virus (EBV) serologies were negative. Viral serologies for hepatitis A, B, and C were negative. Antinuclear antibody (ANA), anti-ds DNA, antineutrophilic cytoplasmic antibody (ANCA), serum angiotensin-converting enzyme (ACE) level, and quantitative immunoglobulin levels were all within the normal range. Chest, abdomen, and pelvis CT with contrast revealed large-volume abdominal and pelvic ascites, diffuse subcutaneous edema (Figure 1), modest hepatosplenomegaly, small bilateral pleural effusions, and mediastinal, axillary, mesenteric, periportal, peripancreatic, and retroperitoneal lymphadenopathy (Figure 2).

Some of the more common viral etiologies of generalized lymphadenopathy and cytopenias are unlikely because serologies for HIV, hepatitis B and C, EBV, and CMV are negative. Tuberculosis fits with the insidious nature of his presentation and remains on the differential although a low SAAG would be expected. From a rheumatologic standpoint, the lack of characteristic findings on history and physical examination and the negative ANA and anti-ds DNA results make SLE unlikely. Although elevated in the majority of untreated sarcoid patients, a normal ACE level is not sufficient to rule out this diagnosis. IgG, IgA, and IgM levels would be low if there was significant gastrointestinal protein loss and elevated in MCD. The markedly increased ferritin level, an acute-phase reactant often elevated in the setting of inflammation or malignancy, raises suspicion for adult Still’s disease (despite the lack of characteristic arthralgias and/or rash) and hemophagocytic lymphohistiocytosis (HLH).

A SAAG greater than or equal to 1.1 indicates the presence of portal hypertension. Portal hypertension most often results from cirrhosis for which this patient has no apparent clinical findings. Etiologies of noncirrhotic portal hypertension are classified as prehepatic, intrahepatic, and posthepatic. There is no clinical or radiologic evidence of portal or splenic vein thrombosis (prehepatic) or heart failure (posthepatic). Possible intrahepatic etiologies include malignancy and sarcoid. Although uncommon, patients with malignancy-related ascites may have a high SAAG without coexisting cirrhosis. This occurs if there is portal hypertension due to extensive metastases in the liver or involvement of the portal venous system. The cytology of the ascitic fluid is negative. However, cytology is <80% sensitive in the absence of peritoneal carcinomatosis.

Hematology was consulted for evaluation of the lymphadenopathy, anemia, and thrombocytopenia and recommended bone marrow and excisional lymph node biopsies. Bone marrow biopsy showed trilineage hypercellularity (Figure 3A) with reduced erythropoiesis and reticulin fibrosis (Figure 3B). An axillary lymph node biopsy with flow cytometry was nondiagnostic for a lymphoproliferative disorder or malignancy.

Five days after discharge, he was readmitted with worsening anasarca, massive ascites, and acute kidney injury. Admission laboratory studies revealed creatinine 1.66 mg/dL, hemoglobin 11.5 g/dL, and platelets 94 k/mm³. In addition, his ferritin level was 1,907 ng/L (reference range, 20-400 ng/L), erythrocyte sedimentation rate (ESR) was 50 mm/h (reference range, 0-20 mm/h), and C-reactive protein concentration (CRP) was 12.1 mg/dL (reference range, 0-0.5 mg/dL).

Steroids are used to treat a wide variety of illnesses, some of which are still under consideration in this patient including lymphoma, MCD, adult Still’s disease, and HLH. His symptoms recurred quickly after discontinuation of steroids in the setting of elevated ferritin, ESR, and CRP levels reflecting marked ongoing inflammation. Serologic testing for soluble IL-2 receptor, often elevated in MCD and HLH, should be performed. Excisional biopsy of an accessible node should be performed urgently.

His acute kidney injury resolved; however, he continued to have intermittent fevers, anemia, thromobocytopenia, lymphadenopathy, and hepatosplenomegaly. A hematology case-conference recommended testing for HLH, including soluble IL-2 receptor (CD25), soluble CD163, and natural killer cell degranulation assay, all of which were negative. A right inguinal lymph node biopsy revealed reactive lymphoid tissue and stained negative for HHV-8. Based on the lack of an alternative diagnosis (particularly lymphoma), the presence of multiple areas of lymphadenopathy, anemia, fevers, organomegaly, weight loss, reactive lymphoid tissue on lymph node biopsy, and elevated CRP and ESR, a working diagnosis of MCD was made. The negative HHV-8 testing was consistent with idiopathic MCD (iMCD); however, features inconsistent with iMCD included lack of polyclonal hypergammaglobulinemia and the presence of significant anasarca and thrombocytopenia. Therefore, an internet search was performed using the patient’s salient symptoms and findings. The search revealed a few recently published case reports of a rare variant of iMCD, TAFRO syndrome. TAFRO syndrome, characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis and/or renal insufficiency, and organomegaly, fully explained the patient’s presentation. He was started on prednisone, rituximab (anti-CD20 antibody), and furosemide. After one month of treatment, he showed complete resolution of cytopenias, lymphadenopathy, organomegaly, anasarca, and ascites. Therapy continued for approximately three months, and he has remained symptom-free.

Castleman’s disease (CD) is a rare lymphoproliferative disorder divided into unicentric (solitary enlarged lymph node) and multicentric (multifocal enlarged lymph nodes).¹ MCD typically presents with systemic inflammation, reactive proliferation of benign lymphocytes, multifocal lymphadenopathy, elevated inflammatory markers, anemia, hypoalbuminemia, and polyclonal gammaglobulinemia.¹ It is hypothesized that HHV-8 drives the systemic inflammation of MCD via high levels of interleukin-6 (IL-6) activity.¹ iMCD is an HHV-8-negative variant of MCD.¹

TAFRO syndrome was first described in 2010 in three Japanese patients demonstrating high fever, anasarca, hepatosplenomegaly, lymphadenopathy, severe thrombocytopenia, and reticulin fibrosis.² In 2015, the All Japan TAFRO Syndrome Research Group recognized TAFRO syndrome as a variant of iMCD and created diagnostic criteria and a severity classification system.³ Major criteria consist of anasarca, including pleural effusion and/or ascites identified on CT scan and general edema, thrombocytopenia (platelet count <100 k/mm³), and systemic inflammation (fever >37.5°C and/or serum CRP greater than or equal to 2 mg/dL).³ Two of four minor criteria must be met, which include (1) lymph node histology consistent with CD, (2) reticulin myelofibrosis and/or increased number of megakaryocytes in bone marrow, (3) mild organomegaly, including hepatomegaly, splenomegaly, and lymphadenopathy <1.5 cm in diameter identified on CT scan, and (4) progressive renal insufficiency (serum creatinine >1.2 mg/dL in males or >1.0 mg/dL in females).³ In addition, several patients with TAFRO syndrome demonstrate elevated ALP, low-normal LDH, elevated vascular endothelial growth factor, elevated IL-6, microcytic anemia, and slight polyclonal hypergammopathy.³ Malignancies such as lymphoma and myeloma, autoimmune diseases such as SLE and ANCA-associated vasculitis, infectious diseases such as those caused by mycobacteria, and POEMS (polyneuropathy, organomegaly, endocrine diseases, M-protein, and skin lesions) syndrome must be excluded to diagnose TAFRO syndrome.^3,4

The pathophysiology of TAFRO syndrome is unknown, and it is unclear whether the syndrome is truly a variant of iMCD or a distinct entity.³ IL-6 is typically only mildly elevated in TAFRO syndrome, without the consequent thrombocytosis and polyclonal hypergammaglobulinemia seen in MCD, which is associated with higher levels of IL-6.¹ Multiple non-HHV-8 mechanisms for TAFRO syndrome have been proposed, including (1) systemic inflammation, autoimmune/autoinflammatory mechanisms, (2) neoplastic, ectopic cytokine secretion by malignant or benign tumor cells, and/or (3) infectious, such as non-HHV-8 virus.⁵

Immunosuppression is the mainstay of treatment for TAFRO syndrome based on recommendations from the 2015 TAFRO Research Group.³ Glucocorticoids are considered first-line therapy.³ Cyclosporin A is recommended for individuals refractory to glucocorticoids.³ In patients with a contraindication to cyclosporin A, anti-IL-6 receptor antibodies such as tocilizumab (approved for treatment of iMCD in Japan) and siltuximab (approved for treatment of iMCD in North America and Europe) or the anti-CD20 antibody rituximab should be prescribed.³ There is evidence for the thrombopoietin receptor agonists romiplostim and eltrombopag to treat persistent thrombocytopenia.³ Additional treatments for refractory TAFRO syndrome include IVIG and plasma exchange, chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone), and thalidomide.^3,6

Little is known about the epidemiologic characterization of TAFRO syndrome as less than 40 cases of TAFRO syndrome have been reported in the United States, Asia, and Europe.

• Key clinical and pathologic features of TAFRO syndrome include thrombocytopenia, anasarca, fever, reticulin fibrosis and/or renal insufficiency, and organomegaly.
• TAFRO syndrome may be under-recognized due to very recent characterization and no previous ICD code for CD.
• TAFRO syndrome experts recommend immunosuppression for treatment of TAFRO syndrome, including glucocorticoids as first-line treatment.
• Internet searches can be helpful in the diagnosis of challenging cases, particularly with rare, unusual, and emerging diseases that have not yet been described in reference texts and only infrequently reported in the medical literature.

Disclosures

Jonathan S. Zipursky, Keri T. Holmes-Maybank, Steven L. Shumak, and Ashley A. Ducketthave none to declare.

A 22-year-old man presented to a Canadian community hospital emergency department complaining of 2-3 weeks of abdominal pain and bloating associated with early satiety. He also noted weight loss of 20 pounds over the preceding months, leg and abdominal swelling with increased girth, and 1-2 loose, nonbloody stools per day.

Early satiety and bloating are nonspecific symptoms that can be due to gastroesophageal reflux disease, peptic ulcer disease, gastrointestinal obstruction, or gastroparesis. Weight loss in a young person, particularly if >5% of body weight, is concerning for a serious underlying medical issue. It could reflect reduced intake due to anorexia, odynophagia, or dysphagia or increased energy expenditure due to an inflammatory state such as infection or rheumatic disease. The etiology of the swelling needs to be elucidated. It may be due to increased hydrostatic forces as in heart failure, venous or lymphatic obstruction, or from lowered oncotic pressure resulting from hepatic disease, nephrotic syndrome, severe malnutrition (nonbloody loose stools), or a protein losing enteropathy.

The patient was transferred to a tertiary care center for closer access to specialty consultation. He described generalized abdominal pain increasing in intensity over three weeks; bilateral lower extremity, scrotal, abdominal wall, and sacral edema; and mild dyspnea on exertion. The early satiety was not associated with dysphagia, odynophagia, nausea, or vomiting. He denied fevers, chills, night sweats, nausea, vomiting, jaundice, easy bruising, orthopnea, paroxysmal nocturnal dyspnea (PND), or chest pain. His past medical history included asthma treated with fluticasone/salmeterol and albuterol. He was a Canadian of East Asian descent working as a plumber. He previously smoked three to four cigarettes per day for six years. He stopped smoking one month before presentation. He had one alcoholic beverage per week and smoked marijuana weekly. He denied any family history of similar symptoms or malignancy.The differential diagnosis for weight loss and anasarca is broad and includes malignancies, infectious diseases, rheumatic or inflammatory disorders, malabsorption, and advanced cardiac, renal, or liver disease. His history does not classically point in one direction. The mild dyspnea on exertion may be due to cardiac disease, but it is unlikely in the absence of orthopnea and PND. The dyspnea could be due to increased abdominal pressure if ascites are present, his underlying asthma, or another etiology such as anemia. Fevers, chills, and/or night sweats can be expected in infections and some malignancies, but their absence does not exclude infections and malignancies from the differential diagnoses. Particular attention should be paid to lymphadenopathy on the physical examination. The presence of an umbilical nodule (Sister Mary Joseph sign) could indicate a malignancy (gastrointestinal or lymphoma).

The differential diagnosis for weight loss and anasarca is broad and includes malignancies, infectious diseases, rheumatic or inflammatory disorders, malabsorption, and advanced cardiac, renal, or liver disease. His history does not classically point in one direction. The mild dyspnea on exertion may be due to cardiac disease, but it is unlikely in the absence of orthopnea and PND. The dyspnea could be due to increased abdominal pressure if ascites are present, his underlying asthma, or another etiology such as anemia. Fevers, chills, and/or night sweats can be expected in infections and some malignancies, but their absence does not exclude infections and malignancies from the differential diagnoses. Particular attention should be paid to lymphadenopathy on the physical examination. The presence of an umbilical nodule (Sister Mary Joseph sign) could indicate a malignancy (gastrointestinal or lymphoma).

On physical examination, his temperature was 38.1°C, heart rate was 138 beats per minute, blood pressure was 123/86 mm Hg, respiratory rate was 20 breaths per minute, and oxygen saturation was 97% on room air. He appeared uncomfortable and diaphoretic. No scleral icterus or jaundice was appreciated. There were no palpable cervical, axillary, or inguinal lymph nodes. Cardiac examination revealed tachycardia and no murmurs, rubs, gallops, or jugular venous distention. Abdominal examination revealed abdominal distention, diffuse tenderness to deep palpation, bulging flanks, and a positive fluid wave. Liver and spleen could not be palpated or percussed secondary to abdominal distention. He had pitting bilateral lower extremity edema that extended to and included the scrotum. Neurologic and pulmonary examinations were unremarkable.

His examination reveals low-grade fever, tachycardia, and diaphoresis. Whether this represents progression of his primary disease or he has acutely developed a superimposed infection is uncertain at this point. He has notable anasarca but no jugular venous distention, crackles, or S3 gallop. The lack of evidence of pulmonary edema or increased central venous pressure on physical examination increases the likelihood of cirrhosis, hypoalbuminemia, or obstruction (lymphatic or venous) and decreases the likelihood of heart failure as the etiology of his peripheral edema and likely ascites. Despite the prominence of gastrointestinal symptoms, he has neither jaundice nor stigmata of chronic liver disease. Periorbital edema, which may be present in nephrotic syndrome, is also absent. Although he has no palpable peripheral lymphadenopathy, malignancy remains a concern.

Testing should include urinalysis for proteinuria and coagulation studies to assess synthetic function of the liver. Abdominal ultrasound is indicated to confirm ascites. If present, a diagnostic paracentesis should be performed to rule out spontaneous bacterial peritonitis and determine whether the ascites is from portal hypertension, hypoalbuminemia, or peritoneal disease. If the transaminases are elevated or if the ascitic fluid is concerning for malignancy, he will need a computed tomography (CT) of the abdomen and pelvis. A protein losing enteropathy due to malignancies (gastric cancer or lymphoma), rheumatic disease (systemic lupus erythematosus [SLE]), or infiltrative disease (amyloid) is also a possibility. If the other studies are unrevealing, stool should be sent for alpha-1 antitrypsin.

Laboratory studies revealed hemoglobin 7.8 g/dL, platelets 53 k/mm³, white blood cell count (WBC) 10.6 k/mm³, alkaline phosphatase (ALP) 217 U/L, albumin 2.7 g/dL, reticulocyte count 3 k/mm³ (reference range, 30-110 k/mm³), and ferritin 1,310 ng/mL (reference range, 20-400 ng/L). Serum aminotransferase levels, bilirubin, coagulation panel, electrolytes, and creatinine were normal. Urinalysis was negative for blood, leukocytes, and protein. Diagnostic paracentesis demonstrated a serum-ascites-albumin gradient (SAAG) of two and macrophage predominance (WBC 250 U/L). Ascitic fluid cytology and culture were negative. Blood cultures, human immunodeficiency virus (HIV)-1 and 2, cytomegalovirus (CMV), and Epstein–Barr virus (EBV) serologies were negative. Viral serologies for hepatitis A, B, and C were negative. Antinuclear antibody (ANA), anti-ds DNA, antineutrophilic cytoplasmic antibody (ANCA), serum angiotensin-converting enzyme (ACE) level, and quantitative immunoglobulin levels were all within the normal range. Chest, abdomen, and pelvis CT with contrast revealed large-volume abdominal and pelvic ascites, diffuse subcutaneous edema (Figure 1), modest hepatosplenomegaly, small bilateral pleural effusions, and mediastinal, axillary, mesenteric, periportal, peripancreatic, and retroperitoneal lymphadenopathy (Figure 2).

Some of the more common viral etiologies of generalized lymphadenopathy and cytopenias are unlikely because serologies for HIV, hepatitis B and C, EBV, and CMV are negative. Tuberculosis fits with the insidious nature of his presentation and remains on the differential although a low SAAG would be expected. From a rheumatologic standpoint, the lack of characteristic findings on history and physical examination and the negative ANA and anti-ds DNA results make SLE unlikely. Although elevated in the majority of untreated sarcoid patients, a normal ACE level is not sufficient to rule out this diagnosis. IgG, IgA, and IgM levels would be low if there was significant gastrointestinal protein loss and elevated in MCD. The markedly increased ferritin level, an acute-phase reactant often elevated in the setting of inflammation or malignancy, raises suspicion for adult Still’s disease (despite the lack of characteristic arthralgias and/or rash) and hemophagocytic lymphohistiocytosis (HLH).

A SAAG greater than or equal to 1.1 indicates the presence of portal hypertension. Portal hypertension most often results from cirrhosis for which this patient has no apparent clinical findings. Etiologies of noncirrhotic portal hypertension are classified as prehepatic, intrahepatic, and posthepatic. There is no clinical or radiologic evidence of portal or splenic vein thrombosis (prehepatic) or heart failure (posthepatic). Possible intrahepatic etiologies include malignancy and sarcoid. Although uncommon, patients with malignancy-related ascites may have a high SAAG without coexisting cirrhosis. This occurs if there is portal hypertension due to extensive metastases in the liver or involvement of the portal venous system. The cytology of the ascitic fluid is negative. However, cytology is <80% sensitive in the absence of peritoneal carcinomatosis.

Hematology was consulted for evaluation of the lymphadenopathy, anemia, and thrombocytopenia and recommended bone marrow and excisional lymph node biopsies. Bone marrow biopsy showed trilineage hypercellularity (Figure 3A) with reduced erythropoiesis and reticulin fibrosis (Figure 3B). An axillary lymph node biopsy with flow cytometry was nondiagnostic for a lymphoproliferative disorder or malignancy.

Five days after discharge, he was readmitted with worsening anasarca, massive ascites, and acute kidney injury. Admission laboratory studies revealed creatinine 1.66 mg/dL, hemoglobin 11.5 g/dL, and platelets 94 k/mm³. In addition, his ferritin level was 1,907 ng/L (reference range, 20-400 ng/L), erythrocyte sedimentation rate (ESR) was 50 mm/h (reference range, 0-20 mm/h), and C-reactive protein concentration (CRP) was 12.1 mg/dL (reference range, 0-0.5 mg/dL).

Steroids are used to treat a wide variety of illnesses, some of which are still under consideration in this patient including lymphoma, MCD, adult Still’s disease, and HLH. His symptoms recurred quickly after discontinuation of steroids in the setting of elevated ferritin, ESR, and CRP levels reflecting marked ongoing inflammation. Serologic testing for soluble IL-2 receptor, often elevated in MCD and HLH, should be performed. Excisional biopsy of an accessible node should be performed urgently.

His acute kidney injury resolved; however, he continued to have intermittent fevers, anemia, thromobocytopenia, lymphadenopathy, and hepatosplenomegaly. A hematology case-conference recommended testing for HLH, including soluble IL-2 receptor (CD25), soluble CD163, and natural killer cell degranulation assay, all of which were negative. A right inguinal lymph node biopsy revealed reactive lymphoid tissue and stained negative for HHV-8. Based on the lack of an alternative diagnosis (particularly lymphoma), the presence of multiple areas of lymphadenopathy, anemia, fevers, organomegaly, weight loss, reactive lymphoid tissue on lymph node biopsy, and elevated CRP and ESR, a working diagnosis of MCD was made. The negative HHV-8 testing was consistent with idiopathic MCD (iMCD); however, features inconsistent with iMCD included lack of polyclonal hypergammaglobulinemia and the presence of significant anasarca and thrombocytopenia. Therefore, an internet search was performed using the patient’s salient symptoms and findings. The search revealed a few recently published case reports of a rare variant of iMCD, TAFRO syndrome. TAFRO syndrome, characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis and/or renal insufficiency, and organomegaly, fully explained the patient’s presentation. He was started on prednisone, rituximab (anti-CD20 antibody), and furosemide. After one month of treatment, he showed complete resolution of cytopenias, lymphadenopathy, organomegaly, anasarca, and ascites. Therapy continued for approximately three months, and he has remained symptom-free.

Castleman’s disease (CD) is a rare lymphoproliferative disorder divided into unicentric (solitary enlarged lymph node) and multicentric (multifocal enlarged lymph nodes).¹ MCD typically presents with systemic inflammation, reactive proliferation of benign lymphocytes, multifocal lymphadenopathy, elevated inflammatory markers, anemia, hypoalbuminemia, and polyclonal gammaglobulinemia.¹ It is hypothesized that HHV-8 drives the systemic inflammation of MCD via high levels of interleukin-6 (IL-6) activity.¹ iMCD is an HHV-8-negative variant of MCD.¹

TAFRO syndrome was first described in 2010 in three Japanese patients demonstrating high fever, anasarca, hepatosplenomegaly, lymphadenopathy, severe thrombocytopenia, and reticulin fibrosis.² In 2015, the All Japan TAFRO Syndrome Research Group recognized TAFRO syndrome as a variant of iMCD and created diagnostic criteria and a severity classification system.³ Major criteria consist of anasarca, including pleural effusion and/or ascites identified on CT scan and general edema, thrombocytopenia (platelet count <100 k/mm³), and systemic inflammation (fever >37.5°C and/or serum CRP greater than or equal to 2 mg/dL).³ Two of four minor criteria must be met, which include (1) lymph node histology consistent with CD, (2) reticulin myelofibrosis and/or increased number of megakaryocytes in bone marrow, (3) mild organomegaly, including hepatomegaly, splenomegaly, and lymphadenopathy <1.5 cm in diameter identified on CT scan, and (4) progressive renal insufficiency (serum creatinine >1.2 mg/dL in males or >1.0 mg/dL in females).³ In addition, several patients with TAFRO syndrome demonstrate elevated ALP, low-normal LDH, elevated vascular endothelial growth factor, elevated IL-6, microcytic anemia, and slight polyclonal hypergammopathy.³ Malignancies such as lymphoma and myeloma, autoimmune diseases such as SLE and ANCA-associated vasculitis, infectious diseases such as those caused by mycobacteria, and POEMS (polyneuropathy, organomegaly, endocrine diseases, M-protein, and skin lesions) syndrome must be excluded to diagnose TAFRO syndrome.^3,4

The pathophysiology of TAFRO syndrome is unknown, and it is unclear whether the syndrome is truly a variant of iMCD or a distinct entity.³ IL-6 is typically only mildly elevated in TAFRO syndrome, without the consequent thrombocytosis and polyclonal hypergammaglobulinemia seen in MCD, which is associated with higher levels of IL-6.¹ Multiple non-HHV-8 mechanisms for TAFRO syndrome have been proposed, including (1) systemic inflammation, autoimmune/autoinflammatory mechanisms, (2) neoplastic, ectopic cytokine secretion by malignant or benign tumor cells, and/or (3) infectious, such as non-HHV-8 virus.⁵

Immunosuppression is the mainstay of treatment for TAFRO syndrome based on recommendations from the 2015 TAFRO Research Group.³ Glucocorticoids are considered first-line therapy.³ Cyclosporin A is recommended for individuals refractory to glucocorticoids.³ In patients with a contraindication to cyclosporin A, anti-IL-6 receptor antibodies such as tocilizumab (approved for treatment of iMCD in Japan) and siltuximab (approved for treatment of iMCD in North America and Europe) or the anti-CD20 antibody rituximab should be prescribed.³ There is evidence for the thrombopoietin receptor agonists romiplostim and eltrombopag to treat persistent thrombocytopenia.³ Additional treatments for refractory TAFRO syndrome include IVIG and plasma exchange, chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone), and thalidomide.^3,6

Little is known about the epidemiologic characterization of TAFRO syndrome as less than 40 cases of TAFRO syndrome have been reported in the United States, Asia, and Europe.

• Key clinical and pathologic features of TAFRO syndrome include thrombocytopenia, anasarca, fever, reticulin fibrosis and/or renal insufficiency, and organomegaly.
• TAFRO syndrome may be under-recognized due to very recent characterization and no previous ICD code for CD.
• TAFRO syndrome experts recommend immunosuppression for treatment of TAFRO syndrome, including glucocorticoids as first-line treatment.
• Internet searches can be helpful in the diagnosis of challenging cases, particularly with rare, unusual, and emerging diseases that have not yet been described in reference texts and only infrequently reported in the medical literature.

Disclosures

Jonathan S. Zipursky, Keri T. Holmes-Maybank, Steven L. Shumak, and Ashley A. Ducketthave none to declare.

A 22-year-old man presented to a Canadian community hospital emergency department complaining of 2-3 weeks of abdominal pain and bloating associated with early satiety. He also noted weight loss of 20 pounds over the preceding months, leg and abdominal swelling with increased girth, and 1-2 loose, nonbloody stools per day.

Early satiety and bloating are nonspecific symptoms that can be due to gastroesophageal reflux disease, peptic ulcer disease, gastrointestinal obstruction, or gastroparesis. Weight loss in a young person, particularly if >5% of body weight, is concerning for a serious underlying medical issue. It could reflect reduced intake due to anorexia, odynophagia, or dysphagia or increased energy expenditure due to an inflammatory state such as infection or rheumatic disease. The etiology of the swelling needs to be elucidated. It may be due to increased hydrostatic forces as in heart failure, venous or lymphatic obstruction, or from lowered oncotic pressure resulting from hepatic disease, nephrotic syndrome, severe malnutrition (nonbloody loose stools), or a protein losing enteropathy.

The patient was transferred to a tertiary care center for closer access to specialty consultation. He described generalized abdominal pain increasing in intensity over three weeks; bilateral lower extremity, scrotal, abdominal wall, and sacral edema; and mild dyspnea on exertion. The early satiety was not associated with dysphagia, odynophagia, nausea, or vomiting. He denied fevers, chills, night sweats, nausea, vomiting, jaundice, easy bruising, orthopnea, paroxysmal nocturnal dyspnea (PND), or chest pain. His past medical history included asthma treated with fluticasone/salmeterol and albuterol. He was a Canadian of East Asian descent working as a plumber. He previously smoked three to four cigarettes per day for six years. He stopped smoking one month before presentation. He had one alcoholic beverage per week and smoked marijuana weekly. He denied any family history of similar symptoms or malignancy.The differential diagnosis for weight loss and anasarca is broad and includes malignancies, infectious diseases, rheumatic or inflammatory disorders, malabsorption, and advanced cardiac, renal, or liver disease. His history does not classically point in one direction. The mild dyspnea on exertion may be due to cardiac disease, but it is unlikely in the absence of orthopnea and PND. The dyspnea could be due to increased abdominal pressure if ascites are present, his underlying asthma, or another etiology such as anemia. Fevers, chills, and/or night sweats can be expected in infections and some malignancies, but their absence does not exclude infections and malignancies from the differential diagnoses. Particular attention should be paid to lymphadenopathy on the physical examination. The presence of an umbilical nodule (Sister Mary Joseph sign) could indicate a malignancy (gastrointestinal or lymphoma).

The differential diagnosis for weight loss and anasarca is broad and includes malignancies, infectious diseases, rheumatic or inflammatory disorders, malabsorption, and advanced cardiac, renal, or liver disease. His history does not classically point in one direction. The mild dyspnea on exertion may be due to cardiac disease, but it is unlikely in the absence of orthopnea and PND. The dyspnea could be due to increased abdominal pressure if ascites are present, his underlying asthma, or another etiology such as anemia. Fevers, chills, and/or night sweats can be expected in infections and some malignancies, but their absence does not exclude infections and malignancies from the differential diagnoses. Particular attention should be paid to lymphadenopathy on the physical examination. The presence of an umbilical nodule (Sister Mary Joseph sign) could indicate a malignancy (gastrointestinal or lymphoma).

On physical examination, his temperature was 38.1°C, heart rate was 138 beats per minute, blood pressure was 123/86 mm Hg, respiratory rate was 20 breaths per minute, and oxygen saturation was 97% on room air. He appeared uncomfortable and diaphoretic. No scleral icterus or jaundice was appreciated. There were no palpable cervical, axillary, or inguinal lymph nodes. Cardiac examination revealed tachycardia and no murmurs, rubs, gallops, or jugular venous distention. Abdominal examination revealed abdominal distention, diffuse tenderness to deep palpation, bulging flanks, and a positive fluid wave. Liver and spleen could not be palpated or percussed secondary to abdominal distention. He had pitting bilateral lower extremity edema that extended to and included the scrotum. Neurologic and pulmonary examinations were unremarkable.

His examination reveals low-grade fever, tachycardia, and diaphoresis. Whether this represents progression of his primary disease or he has acutely developed a superimposed infection is uncertain at this point. He has notable anasarca but no jugular venous distention, crackles, or S3 gallop. The lack of evidence of pulmonary edema or increased central venous pressure on physical examination increases the likelihood of cirrhosis, hypoalbuminemia, or obstruction (lymphatic or venous) and decreases the likelihood of heart failure as the etiology of his peripheral edema and likely ascites. Despite the prominence of gastrointestinal symptoms, he has neither jaundice nor stigmata of chronic liver disease. Periorbital edema, which may be present in nephrotic syndrome, is also absent. Although he has no palpable peripheral lymphadenopathy, malignancy remains a concern.

Testing should include urinalysis for proteinuria and coagulation studies to assess synthetic function of the liver. Abdominal ultrasound is indicated to confirm ascites. If present, a diagnostic paracentesis should be performed to rule out spontaneous bacterial peritonitis and determine whether the ascites is from portal hypertension, hypoalbuminemia, or peritoneal disease. If the transaminases are elevated or if the ascitic fluid is concerning for malignancy, he will need a computed tomography (CT) of the abdomen and pelvis. A protein losing enteropathy due to malignancies (gastric cancer or lymphoma), rheumatic disease (systemic lupus erythematosus [SLE]), or infiltrative disease (amyloid) is also a possibility. If the other studies are unrevealing, stool should be sent for alpha-1 antitrypsin.

Laboratory studies revealed hemoglobin 7.8 g/dL, platelets 53 k/mm³, white blood cell count (WBC) 10.6 k/mm³, alkaline phosphatase (ALP) 217 U/L, albumin 2.7 g/dL, reticulocyte count 3 k/mm³ (reference range, 30-110 k/mm³), and ferritin 1,310 ng/mL (reference range, 20-400 ng/L). Serum aminotransferase levels, bilirubin, coagulation panel, electrolytes, and creatinine were normal. Urinalysis was negative for blood, leukocytes, and protein. Diagnostic paracentesis demonstrated a serum-ascites-albumin gradient (SAAG) of two and macrophage predominance (WBC 250 U/L). Ascitic fluid cytology and culture were negative. Blood cultures, human immunodeficiency virus (HIV)-1 and 2, cytomegalovirus (CMV), and Epstein–Barr virus (EBV) serologies were negative. Viral serologies for hepatitis A, B, and C were negative. Antinuclear antibody (ANA), anti-ds DNA, antineutrophilic cytoplasmic antibody (ANCA), serum angiotensin-converting enzyme (ACE) level, and quantitative immunoglobulin levels were all within the normal range. Chest, abdomen, and pelvis CT with contrast revealed large-volume abdominal and pelvic ascites, diffuse subcutaneous edema (Figure 1), modest hepatosplenomegaly, small bilateral pleural effusions, and mediastinal, axillary, mesenteric, periportal, peripancreatic, and retroperitoneal lymphadenopathy (Figure 2).

Some of the more common viral etiologies of generalized lymphadenopathy and cytopenias are unlikely because serologies for HIV, hepatitis B and C, EBV, and CMV are negative. Tuberculosis fits with the insidious nature of his presentation and remains on the differential although a low SAAG would be expected. From a rheumatologic standpoint, the lack of characteristic findings on history and physical examination and the negative ANA and anti-ds DNA results make SLE unlikely. Although elevated in the majority of untreated sarcoid patients, a normal ACE level is not sufficient to rule out this diagnosis. IgG, IgA, and IgM levels would be low if there was significant gastrointestinal protein loss and elevated in MCD. The markedly increased ferritin level, an acute-phase reactant often elevated in the setting of inflammation or malignancy, raises suspicion for adult Still’s disease (despite the lack of characteristic arthralgias and/or rash) and hemophagocytic lymphohistiocytosis (HLH).

A SAAG greater than or equal to 1.1 indicates the presence of portal hypertension. Portal hypertension most often results from cirrhosis for which this patient has no apparent clinical findings. Etiologies of noncirrhotic portal hypertension are classified as prehepatic, intrahepatic, and posthepatic. There is no clinical or radiologic evidence of portal or splenic vein thrombosis (prehepatic) or heart failure (posthepatic). Possible intrahepatic etiologies include malignancy and sarcoid. Although uncommon, patients with malignancy-related ascites may have a high SAAG without coexisting cirrhosis. This occurs if there is portal hypertension due to extensive metastases in the liver or involvement of the portal venous system. The cytology of the ascitic fluid is negative. However, cytology is <80% sensitive in the absence of peritoneal carcinomatosis.

Hematology was consulted for evaluation of the lymphadenopathy, anemia, and thrombocytopenia and recommended bone marrow and excisional lymph node biopsies. Bone marrow biopsy showed trilineage hypercellularity (Figure 3A) with reduced erythropoiesis and reticulin fibrosis (Figure 3B). An axillary lymph node biopsy with flow cytometry was nondiagnostic for a lymphoproliferative disorder or malignancy.

Five days after discharge, he was readmitted with worsening anasarca, massive ascites, and acute kidney injury. Admission laboratory studies revealed creatinine 1.66 mg/dL, hemoglobin 11.5 g/dL, and platelets 94 k/mm³. In addition, his ferritin level was 1,907 ng/L (reference range, 20-400 ng/L), erythrocyte sedimentation rate (ESR) was 50 mm/h (reference range, 0-20 mm/h), and C-reactive protein concentration (CRP) was 12.1 mg/dL (reference range, 0-0.5 mg/dL).

Steroids are used to treat a wide variety of illnesses, some of which are still under consideration in this patient including lymphoma, MCD, adult Still’s disease, and HLH. His symptoms recurred quickly after discontinuation of steroids in the setting of elevated ferritin, ESR, and CRP levels reflecting marked ongoing inflammation. Serologic testing for soluble IL-2 receptor, often elevated in MCD and HLH, should be performed. Excisional biopsy of an accessible node should be performed urgently.

His acute kidney injury resolved; however, he continued to have intermittent fevers, anemia, thromobocytopenia, lymphadenopathy, and hepatosplenomegaly. A hematology case-conference recommended testing for HLH, including soluble IL-2 receptor (CD25), soluble CD163, and natural killer cell degranulation assay, all of which were negative. A right inguinal lymph node biopsy revealed reactive lymphoid tissue and stained negative for HHV-8. Based on the lack of an alternative diagnosis (particularly lymphoma), the presence of multiple areas of lymphadenopathy, anemia, fevers, organomegaly, weight loss, reactive lymphoid tissue on lymph node biopsy, and elevated CRP and ESR, a working diagnosis of MCD was made. The negative HHV-8 testing was consistent with idiopathic MCD (iMCD); however, features inconsistent with iMCD included lack of polyclonal hypergammaglobulinemia and the presence of significant anasarca and thrombocytopenia. Therefore, an internet search was performed using the patient’s salient symptoms and findings. The search revealed a few recently published case reports of a rare variant of iMCD, TAFRO syndrome. TAFRO syndrome, characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis and/or renal insufficiency, and organomegaly, fully explained the patient’s presentation. He was started on prednisone, rituximab (anti-CD20 antibody), and furosemide. After one month of treatment, he showed complete resolution of cytopenias, lymphadenopathy, organomegaly, anasarca, and ascites. Therapy continued for approximately three months, and he has remained symptom-free.

Castleman’s disease (CD) is a rare lymphoproliferative disorder divided into unicentric (solitary enlarged lymph node) and multicentric (multifocal enlarged lymph nodes).¹ MCD typically presents with systemic inflammation, reactive proliferation of benign lymphocytes, multifocal lymphadenopathy, elevated inflammatory markers, anemia, hypoalbuminemia, and polyclonal gammaglobulinemia.¹ It is hypothesized that HHV-8 drives the systemic inflammation of MCD via high levels of interleukin-6 (IL-6) activity.¹ iMCD is an HHV-8-negative variant of MCD.¹

TAFRO syndrome was first described in 2010 in three Japanese patients demonstrating high fever, anasarca, hepatosplenomegaly, lymphadenopathy, severe thrombocytopenia, and reticulin fibrosis.² In 2015, the All Japan TAFRO Syndrome Research Group recognized TAFRO syndrome as a variant of iMCD and created diagnostic criteria and a severity classification system.³ Major criteria consist of anasarca, including pleural effusion and/or ascites identified on CT scan and general edema, thrombocytopenia (platelet count <100 k/mm³), and systemic inflammation (fever >37.5°C and/or serum CRP greater than or equal to 2 mg/dL).³ Two of four minor criteria must be met, which include (1) lymph node histology consistent with CD, (2) reticulin myelofibrosis and/or increased number of megakaryocytes in bone marrow, (3) mild organomegaly, including hepatomegaly, splenomegaly, and lymphadenopathy <1.5 cm in diameter identified on CT scan, and (4) progressive renal insufficiency (serum creatinine >1.2 mg/dL in males or >1.0 mg/dL in females).³ In addition, several patients with TAFRO syndrome demonstrate elevated ALP, low-normal LDH, elevated vascular endothelial growth factor, elevated IL-6, microcytic anemia, and slight polyclonal hypergammopathy.³ Malignancies such as lymphoma and myeloma, autoimmune diseases such as SLE and ANCA-associated vasculitis, infectious diseases such as those caused by mycobacteria, and POEMS (polyneuropathy, organomegaly, endocrine diseases, M-protein, and skin lesions) syndrome must be excluded to diagnose TAFRO syndrome.^3,4

The pathophysiology of TAFRO syndrome is unknown, and it is unclear whether the syndrome is truly a variant of iMCD or a distinct entity.³ IL-6 is typically only mildly elevated in TAFRO syndrome, without the consequent thrombocytosis and polyclonal hypergammaglobulinemia seen in MCD, which is associated with higher levels of IL-6.¹ Multiple non-HHV-8 mechanisms for TAFRO syndrome have been proposed, including (1) systemic inflammation, autoimmune/autoinflammatory mechanisms, (2) neoplastic, ectopic cytokine secretion by malignant or benign tumor cells, and/or (3) infectious, such as non-HHV-8 virus.⁵

Immunosuppression is the mainstay of treatment for TAFRO syndrome based on recommendations from the 2015 TAFRO Research Group.³ Glucocorticoids are considered first-line therapy.³ Cyclosporin A is recommended for individuals refractory to glucocorticoids.³ In patients with a contraindication to cyclosporin A, anti-IL-6 receptor antibodies such as tocilizumab (approved for treatment of iMCD in Japan) and siltuximab (approved for treatment of iMCD in North America and Europe) or the anti-CD20 antibody rituximab should be prescribed.³ There is evidence for the thrombopoietin receptor agonists romiplostim and eltrombopag to treat persistent thrombocytopenia.³ Additional treatments for refractory TAFRO syndrome include IVIG and plasma exchange, chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone), and thalidomide.^3,6

Little is known about the epidemiologic characterization of TAFRO syndrome as less than 40 cases of TAFRO syndrome have been reported in the United States, Asia, and Europe.

• Key clinical and pathologic features of TAFRO syndrome include thrombocytopenia, anasarca, fever, reticulin fibrosis and/or renal insufficiency, and organomegaly.
• TAFRO syndrome may be under-recognized due to very recent characterization and no previous ICD code for CD.
• TAFRO syndrome experts recommend immunosuppression for treatment of TAFRO syndrome, including glucocorticoids as first-line treatment.
• Internet searches can be helpful in the diagnosis of challenging cases, particularly with rare, unusual, and emerging diseases that have not yet been described in reference texts and only infrequently reported in the medical literature.

Disclosures

Jonathan S. Zipursky, Keri T. Holmes-Maybank, Steven L. Shumak, and Ashley A. Ducketthave none to declare.

There are differences in how pulmonologists and other clinicians approach the diagnosis and management of patients with moderate to severe asthma, according to a survey conducted by Medscape in collaboration with CHEST, the American College of Chest Physicians. Despite some of these differences, those surveyed do predominantly favor similar treatment options, including inhaled corticosteroids and biologics. Biologics in particular are perceived as a promising therapeutic approach for moderate to severe asthma by clinicians overall, and many are also comfortable prescribing them.

Medscape and CHEST asked 763 clinicians about their views on moderate to severe asthma. Responses came from 100 pulmonologists; 102 allergists/immunologists; 102 critical care medicine physicians; 100 emergency medicine (EM) physicians; 104 pediatricians; 100 primary care physicians (PCPs); and 155 nurse practitioners (NPs), physician assistants (PAs), or registered nurses (RNs).

Inhaled Steroids Top Treatment Choice

Survey respondents ranked an inhaled corticosteroid with a long-acting bronchodilator as the favored medication for patients with moderate to severe asthma; 83% of allergists/immunologists feel this way, as do between 52% and 63% of the other clinicians, including pulmonologists.

Inhaled corticosteroids alone are generally preferred by 23%-28% of clinicians surveyed, with the exception of allergists/immunologists (12%). EM physicians (19%) and pediatricians (16%) tend to more often favor an inhaled corticosteroid and leukotriene-modifying agent than do other clinicians, but notably, none of the allergists/immunologists felt this way.

 

Biologics Are an Important Step Forward

When it comes to biologic agents for moderate to severe asthma, it is allergists/immunologists (91%) who say they are most comfortable prescribing them. This percentage drops to 59% for pulmonologists, 34% for NP/PA/RNs, 20% for critical care medicine physicians, 16% for PCPs, 7% for pediatricians, and just 2% of EM physicians

Aaron B. Holley, MD, FCCP, program director at the Pulmonary and Critical Care Medical Fellowship, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, and a member of the Moderate to Severe Asthma Center of Excellence steering committee, noted that the latest rage is to personalize treatment by “phenotyping” asthma, with the thought being that certain asthma phenotypes will respond well to some treatments, but not to others. “This sounds good in academic and scientific papers, but remains difficult to operationalize in the clinic,” said Holley.

He also noted that the new biologics all target one specific phenotype: eosinophilic asthma. “This phenotype makes up approximately 50% of all patients with asthma; however, the other 50% have no targeted treatments available, and they don’t necessarily respond well to conventional inhaler therapy,” said Holley.

And for patients with severe, poorly responsive asthma, it’s hard to say precisely what percentage is being treated inappropriately for their phenotype, versus what percentage is noncompliant, versus what percentage is due to socioeconomic status and behavioral health issues, he noted.

The solution? “There is no easy solution,” said Holley. “More specialized, severe asthma clinics? Greater education on inhaler use and disease severity? Concomitant management of behavioral health complaints? All these are necessary, but they’re also resource-intensive.”

Still, in his view, the glass is half-full. “The biologics are an important step forward, and we’re getting better at phenotyping. Compared with 5-10 years ago, we’re in a much better place.”

Preferred Biomarkers

Familiarity with biomarkers for moderate or severe asthma is universal among pulmonologists. Only 2% of allergists/immunologists are not familiar with biomarkers, compared with nearly three quarters of EM physicians, 45% of pediatricians, 36% of PCPs, 31% of NP/PA/RNs, and 20% of critical care medicine physicians.

Immunoglobulin E (IgE) levels ranked as the most important biomarker for moderate or severe asthma, favored by 47% of pulmonologists and 50% of allergists/immunologists, followed by eosinophils, preferred by 44% of pulmonologists and 38% of allergists/immunologists. Between 26% and 36% of other clinicians rank IgE tops, except for EM physicians (13%). About one third of critical care medicine physicians and one quarter of PCPs and NP/PA/RNs think eosinophils are the most important biomarker, compared with only 14% of pediatricians and 10% of EM physicians.

Fraction of exhaled nitric oxide (FeNO) is least favored by all clinicians surveyed. Just 9% of pulmonologists, 12% of allergists/immunologists, and 5% of EM physicians like this biomarker. Pediatricians ranked FeNO the highest among those surveyed, but only at 14%.

 

Assessment Tools and Guidelines

One “interesting” finding is the difference between specialties in use of the Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ), commented Holley. Most pulmonologists (57%) and allergists/immunologists (79%) favor ACTs for adults and children, whereas other clinicians seem to favor the ACQ.

Both the ACT and ACQ have decent literature to support their use, he noted. “I use the ACT, but personally, I don’t think it makes a difference which you use. I do think it’s important to get an objective score for their subjective symptoms to facilitate tracking over time, and to ensure that clinicians are speaking the same language. For example, if someone else sees my patient for some reason, one look at the ACT score will summarize their disease control, as opposed to them having to pull it out of a running narrative history,” said Holley.

ACTs are also favored by 39% of NP/PA/RNs, 34% of pediatricians, 27% of PCPs, 16% of critical care medicine physicians, and just 6% of EM physicians. About one third of EM physicians and PCPs (34% each) favor the ACQ, as do 30% of NP/PA/RNs, 29% of pediatricians, 20% of pulmonologists, 17% of allergists/immunologists, and 8% of EM physicians.
 

Thirty-six percent of all clinicians said they don’t use any assessment tool to gauge asthma control in patients with moderate to severe asthma, including 86% of EM physicians and 42% of PCPs – the specialties most apt to report no use.

As for guideline use, 83% of allergists/immunologists and 81% of pediatricians surveyed use the National Asthma Education and Prevention Program (NAEPP) guidelines. Pulmonologists tend to use these guidelines less often (37%), as they also rely on the Global Initiative for Asthma (GINA) (54%) and European Respiratory Society (ERS)/American Thoracic Society (ATS) guidelines (43%).

About two thirds (62%) of NP/PA/RNs favor the NAEPP guidelines, as do 49% of PCPs and critical care medicine physicians and 31% of EM physicians. Sixty percent of EM physicians don’t use guidelines at all.

 

Chief Culprits Behind Poor Asthma Control

Clinicians tend to see a lack of appropriate treatment as the greatest barrier for patients with moderate to severe asthma; 63% of pulmonologists feel this way, as do 60% of allergists/immunologists, 52% of PCPs, 50% of pediatricians, and 45% of NP/PA/RNs, compared with just 32% of EM and critical care medicine physicians. EM (67%) and critical care medicine (54%) physicians are also more apt to think that the patient not seeing a provider is the greatest barrier.

Overall, most clinicians surveyed link poor asthma control to poor medication adherence and social or environmental risk irritants, such as smoking, secondhand smoke exposure, vaping, and pollutants.

“No surprise here,” said Holley. “In my experience, medication adherence and environmental risks or irritants are big factors in patients with moderate to severe asthma who don’t respond to conventional, standard asthma treatment and continue to progress.”

“We know from data that poor control is related to socioeconomic status and behavioral health. We also know that proper inhaler use and compliance are a big problem. Does this account for most ‘progression’? That’s hard to say, I suppose, but certainly these are big factors,” Holley added.

Echoing Holley, Navitha Ramesh, MD, clinical assistant professor of medicine at the Department of Clinical Sciences, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, who is also a member of the Moderate to Severe Asthma Center of Excellence steering committee, said the biggest barriers to treatment, in her experience, are “poor health literacy, medication nonadherence, poor social support, and tobacco use.”

The survey was conducted August 29, 2018, to October 11, 2018. Pulmonologists were recruited from CHEST, and all other clinicians were recruited from Medscape members. Patients with moderate to severe asthma account for at least half of all patients with asthma seen by pulmonologists, allergists/immunologists, and critical care medicine physicians; this proportion falls to about 30% among pediatricians and PCPs. Of the clinicians surveyed, patients with moderate to severe asthma are overwhelmingly referred to pulmonologists. Among the reasons for referral are multiple emergency department visits, poor control, failure on first-line therapy, and confounding factors.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube

There are differences in how pulmonologists and other clinicians approach the diagnosis and management of patients with moderate to severe asthma, according to a survey conducted by Medscape in collaboration with CHEST, the American College of Chest Physicians. Despite some of these differences, those surveyed do predominantly favor similar treatment options, including inhaled corticosteroids and biologics. Biologics in particular are perceived as a promising therapeutic approach for moderate to severe asthma by clinicians overall, and many are also comfortable prescribing them.

Medscape and CHEST asked 763 clinicians about their views on moderate to severe asthma. Responses came from 100 pulmonologists; 102 allergists/immunologists; 102 critical care medicine physicians; 100 emergency medicine (EM) physicians; 104 pediatricians; 100 primary care physicians (PCPs); and 155 nurse practitioners (NPs), physician assistants (PAs), or registered nurses (RNs).

Inhaled Steroids Top Treatment Choice

Survey respondents ranked an inhaled corticosteroid with a long-acting bronchodilator as the favored medication for patients with moderate to severe asthma; 83% of allergists/immunologists feel this way, as do between 52% and 63% of the other clinicians, including pulmonologists.

Inhaled corticosteroids alone are generally preferred by 23%-28% of clinicians surveyed, with the exception of allergists/immunologists (12%). EM physicians (19%) and pediatricians (16%) tend to more often favor an inhaled corticosteroid and leukotriene-modifying agent than do other clinicians, but notably, none of the allergists/immunologists felt this way.

 

Biologics Are an Important Step Forward

When it comes to biologic agents for moderate to severe asthma, it is allergists/immunologists (91%) who say they are most comfortable prescribing them. This percentage drops to 59% for pulmonologists, 34% for NP/PA/RNs, 20% for critical care medicine physicians, 16% for PCPs, 7% for pediatricians, and just 2% of EM physicians

Aaron B. Holley, MD, FCCP, program director at the Pulmonary and Critical Care Medical Fellowship, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, and a member of the Moderate to Severe Asthma Center of Excellence steering committee, noted that the latest rage is to personalize treatment by “phenotyping” asthma, with the thought being that certain asthma phenotypes will respond well to some treatments, but not to others. “This sounds good in academic and scientific papers, but remains difficult to operationalize in the clinic,” said Holley.

He also noted that the new biologics all target one specific phenotype: eosinophilic asthma. “This phenotype makes up approximately 50% of all patients with asthma; however, the other 50% have no targeted treatments available, and they don’t necessarily respond well to conventional inhaler therapy,” said Holley.

And for patients with severe, poorly responsive asthma, it’s hard to say precisely what percentage is being treated inappropriately for their phenotype, versus what percentage is noncompliant, versus what percentage is due to socioeconomic status and behavioral health issues, he noted.

The solution? “There is no easy solution,” said Holley. “More specialized, severe asthma clinics? Greater education on inhaler use and disease severity? Concomitant management of behavioral health complaints? All these are necessary, but they’re also resource-intensive.”

Still, in his view, the glass is half-full. “The biologics are an important step forward, and we’re getting better at phenotyping. Compared with 5-10 years ago, we’re in a much better place.”

Preferred Biomarkers

Familiarity with biomarkers for moderate or severe asthma is universal among pulmonologists. Only 2% of allergists/immunologists are not familiar with biomarkers, compared with nearly three quarters of EM physicians, 45% of pediatricians, 36% of PCPs, 31% of NP/PA/RNs, and 20% of critical care medicine physicians.

Immunoglobulin E (IgE) levels ranked as the most important biomarker for moderate or severe asthma, favored by 47% of pulmonologists and 50% of allergists/immunologists, followed by eosinophils, preferred by 44% of pulmonologists and 38% of allergists/immunologists. Between 26% and 36% of other clinicians rank IgE tops, except for EM physicians (13%). About one third of critical care medicine physicians and one quarter of PCPs and NP/PA/RNs think eosinophils are the most important biomarker, compared with only 14% of pediatricians and 10% of EM physicians.

Fraction of exhaled nitric oxide (FeNO) is least favored by all clinicians surveyed. Just 9% of pulmonologists, 12% of allergists/immunologists, and 5% of EM physicians like this biomarker. Pediatricians ranked FeNO the highest among those surveyed, but only at 14%.

 

Assessment Tools and Guidelines

One “interesting” finding is the difference between specialties in use of the Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ), commented Holley. Most pulmonologists (57%) and allergists/immunologists (79%) favor ACTs for adults and children, whereas other clinicians seem to favor the ACQ.

Both the ACT and ACQ have decent literature to support their use, he noted. “I use the ACT, but personally, I don’t think it makes a difference which you use. I do think it’s important to get an objective score for their subjective symptoms to facilitate tracking over time, and to ensure that clinicians are speaking the same language. For example, if someone else sees my patient for some reason, one look at the ACT score will summarize their disease control, as opposed to them having to pull it out of a running narrative history,” said Holley.

ACTs are also favored by 39% of NP/PA/RNs, 34% of pediatricians, 27% of PCPs, 16% of critical care medicine physicians, and just 6% of EM physicians. About one third of EM physicians and PCPs (34% each) favor the ACQ, as do 30% of NP/PA/RNs, 29% of pediatricians, 20% of pulmonologists, 17% of allergists/immunologists, and 8% of EM physicians.
 

Thirty-six percent of all clinicians said they don’t use any assessment tool to gauge asthma control in patients with moderate to severe asthma, including 86% of EM physicians and 42% of PCPs – the specialties most apt to report no use.

As for guideline use, 83% of allergists/immunologists and 81% of pediatricians surveyed use the National Asthma Education and Prevention Program (NAEPP) guidelines. Pulmonologists tend to use these guidelines less often (37%), as they also rely on the Global Initiative for Asthma (GINA) (54%) and European Respiratory Society (ERS)/American Thoracic Society (ATS) guidelines (43%).

About two thirds (62%) of NP/PA/RNs favor the NAEPP guidelines, as do 49% of PCPs and critical care medicine physicians and 31% of EM physicians. Sixty percent of EM physicians don’t use guidelines at all.

 

Chief Culprits Behind Poor Asthma Control

Clinicians tend to see a lack of appropriate treatment as the greatest barrier for patients with moderate to severe asthma; 63% of pulmonologists feel this way, as do 60% of allergists/immunologists, 52% of PCPs, 50% of pediatricians, and 45% of NP/PA/RNs, compared with just 32% of EM and critical care medicine physicians. EM (67%) and critical care medicine (54%) physicians are also more apt to think that the patient not seeing a provider is the greatest barrier.

Overall, most clinicians surveyed link poor asthma control to poor medication adherence and social or environmental risk irritants, such as smoking, secondhand smoke exposure, vaping, and pollutants.

“No surprise here,” said Holley. “In my experience, medication adherence and environmental risks or irritants are big factors in patients with moderate to severe asthma who don’t respond to conventional, standard asthma treatment and continue to progress.”

“We know from data that poor control is related to socioeconomic status and behavioral health. We also know that proper inhaler use and compliance are a big problem. Does this account for most ‘progression’? That’s hard to say, I suppose, but certainly these are big factors,” Holley added.

Echoing Holley, Navitha Ramesh, MD, clinical assistant professor of medicine at the Department of Clinical Sciences, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, who is also a member of the Moderate to Severe Asthma Center of Excellence steering committee, said the biggest barriers to treatment, in her experience, are “poor health literacy, medication nonadherence, poor social support, and tobacco use.”

The survey was conducted August 29, 2018, to October 11, 2018. Pulmonologists were recruited from CHEST, and all other clinicians were recruited from Medscape members. Patients with moderate to severe asthma account for at least half of all patients with asthma seen by pulmonologists, allergists/immunologists, and critical care medicine physicians; this proportion falls to about 30% among pediatricians and PCPs. Of the clinicians surveyed, patients with moderate to severe asthma are overwhelmingly referred to pulmonologists. Among the reasons for referral are multiple emergency department visits, poor control, failure on first-line therapy, and confounding factors.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube

There are differences in how pulmonologists and other clinicians approach the diagnosis and management of patients with moderate to severe asthma, according to a survey conducted by Medscape in collaboration with CHEST, the American College of Chest Physicians. Despite some of these differences, those surveyed do predominantly favor similar treatment options, including inhaled corticosteroids and biologics. Biologics in particular are perceived as a promising therapeutic approach for moderate to severe asthma by clinicians overall, and many are also comfortable prescribing them.

Medscape and CHEST asked 763 clinicians about their views on moderate to severe asthma. Responses came from 100 pulmonologists; 102 allergists/immunologists; 102 critical care medicine physicians; 100 emergency medicine (EM) physicians; 104 pediatricians; 100 primary care physicians (PCPs); and 155 nurse practitioners (NPs), physician assistants (PAs), or registered nurses (RNs).

Inhaled Steroids Top Treatment Choice

Survey respondents ranked an inhaled corticosteroid with a long-acting bronchodilator as the favored medication for patients with moderate to severe asthma; 83% of allergists/immunologists feel this way, as do between 52% and 63% of the other clinicians, including pulmonologists.

Inhaled corticosteroids alone are generally preferred by 23%-28% of clinicians surveyed, with the exception of allergists/immunologists (12%). EM physicians (19%) and pediatricians (16%) tend to more often favor an inhaled corticosteroid and leukotriene-modifying agent than do other clinicians, but notably, none of the allergists/immunologists felt this way.

 

Biologics Are an Important Step Forward

When it comes to biologic agents for moderate to severe asthma, it is allergists/immunologists (91%) who say they are most comfortable prescribing them. This percentage drops to 59% for pulmonologists, 34% for NP/PA/RNs, 20% for critical care medicine physicians, 16% for PCPs, 7% for pediatricians, and just 2% of EM physicians

Aaron B. Holley, MD, FCCP, program director at the Pulmonary and Critical Care Medical Fellowship, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, and a member of the Moderate to Severe Asthma Center of Excellence steering committee, noted that the latest rage is to personalize treatment by “phenotyping” asthma, with the thought being that certain asthma phenotypes will respond well to some treatments, but not to others. “This sounds good in academic and scientific papers, but remains difficult to operationalize in the clinic,” said Holley.

He also noted that the new biologics all target one specific phenotype: eosinophilic asthma. “This phenotype makes up approximately 50% of all patients with asthma; however, the other 50% have no targeted treatments available, and they don’t necessarily respond well to conventional inhaler therapy,” said Holley.

And for patients with severe, poorly responsive asthma, it’s hard to say precisely what percentage is being treated inappropriately for their phenotype, versus what percentage is noncompliant, versus what percentage is due to socioeconomic status and behavioral health issues, he noted.

The solution? “There is no easy solution,” said Holley. “More specialized, severe asthma clinics? Greater education on inhaler use and disease severity? Concomitant management of behavioral health complaints? All these are necessary, but they’re also resource-intensive.”

Still, in his view, the glass is half-full. “The biologics are an important step forward, and we’re getting better at phenotyping. Compared with 5-10 years ago, we’re in a much better place.”

Preferred Biomarkers

Familiarity with biomarkers for moderate or severe asthma is universal among pulmonologists. Only 2% of allergists/immunologists are not familiar with biomarkers, compared with nearly three quarters of EM physicians, 45% of pediatricians, 36% of PCPs, 31% of NP/PA/RNs, and 20% of critical care medicine physicians.

Immunoglobulin E (IgE) levels ranked as the most important biomarker for moderate or severe asthma, favored by 47% of pulmonologists and 50% of allergists/immunologists, followed by eosinophils, preferred by 44% of pulmonologists and 38% of allergists/immunologists. Between 26% and 36% of other clinicians rank IgE tops, except for EM physicians (13%). About one third of critical care medicine physicians and one quarter of PCPs and NP/PA/RNs think eosinophils are the most important biomarker, compared with only 14% of pediatricians and 10% of EM physicians.

Fraction of exhaled nitric oxide (FeNO) is least favored by all clinicians surveyed. Just 9% of pulmonologists, 12% of allergists/immunologists, and 5% of EM physicians like this biomarker. Pediatricians ranked FeNO the highest among those surveyed, but only at 14%.

 

Assessment Tools and Guidelines

One “interesting” finding is the difference between specialties in use of the Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ), commented Holley. Most pulmonologists (57%) and allergists/immunologists (79%) favor ACTs for adults and children, whereas other clinicians seem to favor the ACQ.

Both the ACT and ACQ have decent literature to support their use, he noted. “I use the ACT, but personally, I don’t think it makes a difference which you use. I do think it’s important to get an objective score for their subjective symptoms to facilitate tracking over time, and to ensure that clinicians are speaking the same language. For example, if someone else sees my patient for some reason, one look at the ACT score will summarize their disease control, as opposed to them having to pull it out of a running narrative history,” said Holley.

ACTs are also favored by 39% of NP/PA/RNs, 34% of pediatricians, 27% of PCPs, 16% of critical care medicine physicians, and just 6% of EM physicians. About one third of EM physicians and PCPs (34% each) favor the ACQ, as do 30% of NP/PA/RNs, 29% of pediatricians, 20% of pulmonologists, 17% of allergists/immunologists, and 8% of EM physicians.
 

Thirty-six percent of all clinicians said they don’t use any assessment tool to gauge asthma control in patients with moderate to severe asthma, including 86% of EM physicians and 42% of PCPs – the specialties most apt to report no use.

As for guideline use, 83% of allergists/immunologists and 81% of pediatricians surveyed use the National Asthma Education and Prevention Program (NAEPP) guidelines. Pulmonologists tend to use these guidelines less often (37%), as they also rely on the Global Initiative for Asthma (GINA) (54%) and European Respiratory Society (ERS)/American Thoracic Society (ATS) guidelines (43%).

About two thirds (62%) of NP/PA/RNs favor the NAEPP guidelines, as do 49% of PCPs and critical care medicine physicians and 31% of EM physicians. Sixty percent of EM physicians don’t use guidelines at all.

 

Chief Culprits Behind Poor Asthma Control

Clinicians tend to see a lack of appropriate treatment as the greatest barrier for patients with moderate to severe asthma; 63% of pulmonologists feel this way, as do 60% of allergists/immunologists, 52% of PCPs, 50% of pediatricians, and 45% of NP/PA/RNs, compared with just 32% of EM and critical care medicine physicians. EM (67%) and critical care medicine (54%) physicians are also more apt to think that the patient not seeing a provider is the greatest barrier.

Overall, most clinicians surveyed link poor asthma control to poor medication adherence and social or environmental risk irritants, such as smoking, secondhand smoke exposure, vaping, and pollutants.

“No surprise here,” said Holley. “In my experience, medication adherence and environmental risks or irritants are big factors in patients with moderate to severe asthma who don’t respond to conventional, standard asthma treatment and continue to progress.”

“We know from data that poor control is related to socioeconomic status and behavioral health. We also know that proper inhaler use and compliance are a big problem. Does this account for most ‘progression’? That’s hard to say, I suppose, but certainly these are big factors,” Holley added.

Echoing Holley, Navitha Ramesh, MD, clinical assistant professor of medicine at the Department of Clinical Sciences, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, who is also a member of the Moderate to Severe Asthma Center of Excellence steering committee, said the biggest barriers to treatment, in her experience, are “poor health literacy, medication nonadherence, poor social support, and tobacco use.”

The survey was conducted August 29, 2018, to October 11, 2018. Pulmonologists were recruited from CHEST, and all other clinicians were recruited from Medscape members. Patients with moderate to severe asthma account for at least half of all patients with asthma seen by pulmonologists, allergists/immunologists, and critical care medicine physicians; this proportion falls to about 30% among pediatricians and PCPs. Of the clinicians surveyed, patients with moderate to severe asthma are overwhelmingly referred to pulmonologists. Among the reasons for referral are multiple emergency department visits, poor control, failure on first-line therapy, and confounding factors.

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In a study highlighted in a recent issue of CHEST Physician, Hou and colleagues analyzed complications from biopsies of lung abnormalities seen on CT scans by conducting a large retrospective study with data gleaned from national databases of patients undergoing CT- guided biopsy, surgery, or bronchoscopy.¹ While it should not be interpreted as representative of a lung cancer screening population (for excellent comments by Drs. Rivera and Silvestri regarding the study, see: https://tinyurl.com/y52ucb94), it does raises two important questions when performing shared decision-making for low dose CT (LDCT) scanning: (1) What information should clinicians discuss with patients regarding various biopsy methods until more data are available? (2) How do we mitigate complications from biopsies?

While procedure-specific biopsy risk may be generalizable, it may be institutionally specific, and knowledge of local skill and outcomes data can help guide discussions. With that said, some general information can inform decisions. The NAVIGATE study investigators recently published their 1-year follow-up results using a navigational bronchoscopy system (superDimension^™). While inherent limitations to this study exist, it does provide some useful information as to procedure-related complications from a large sample of patients who approximate a lung cancer screening population. This group was composed of both academic and community centers and prospectively followed 1,215 patients for 1 year.² The average age of the population was 67.6 (± 11.3), and 80% were current or former smokers. The median nodule size was 2 cm. The diagnostic yield was 73% at 1 year follow-up (data will be re-analyzed at 2 years). The pneumothorax rate was 4%, with 3% requiring chest tube. Hemorrhage occurred in 2.5% of all patients, with 1.5% having a common terminology criteria for adverse events (CTCAE) ≥ 2. Grade 4 respiratory failure occurred in 1 patient. There were no ENB procedure-related deaths. It should be noted that individuals performing these procedures were, by and large, high-volume and experienced users.

In comparison, the overall pooled sensitivity for CT scan-guided biopsy is 90% for pulmonary nodules and masses. The yield is lower, however, for smaller lesions (≤2.0) and ranges from 74% to 77%.³ The average pneumothorax rate is 20%, with 1% to 3% requiring chest tube placement. Risk factors for pneumothorax vary between studies, but, generally speaking, have been associated with nodules ≤ 2 cm, those within 2 cm of the pleura (but not abutting the pleura), and emphysema in the track of needle trajectory. Pulmonary hemorrhage occurs 30% of the time but is mild in most cases. Hemoptysis and severe hemorrhage occur at rates of 4% and <1%, respectively. Risk factors for development of pulmonary hemorrhage include small lesion size (< 2 cm) and lesions > 2 cm from the pleura.

When considering surgical lung biopsies and resection, recent data suggest every effort should be made to encourage smoking cessation in order to mitigate postoperative morbidity. In a retrospective study by Fukui and colleagues,⁴ respiratory morbidity (defined as hypoxia, pneumonia, atelectasis, and uncontrolled sputum production) was 22% in smokers vs 3.5% in never smokers. The rate of complications decreased as the time from smoking cessation to date of surgery increased.

The goal for each patient who is counseled should be to limit the number of procedures and achieve the greatest diagnostic confidence with the lowest complication rate. With these risks and diagnostic yield in mind, the decision to recommend a particular biopsy strategy (or no biopsy at all) should be based on current guideline recommendations: (1) patient co-morbidities and preferences; (2) size of index nodule or mass; (3) presence of pathologically enlarged mediastinal and/or hilar lymphadenopathy; (4) evidence of extrathoracic metastasis; and (5) institutional expertise. Specifically speaking for the pulmonologist, this translates into identifying specific procedural “champions” who are dedicated to performing these procedures and are members of a multidisciplinary thoracic team. These individuals should have dedicated training in advanced diagnostic procedures to achieve the aforementioned goals.⁵ The same should hold true for transthoracic, CT-guided biopsies. Interventional pulmonology fellowships are structured to provide exposure to multidisciplinary nodule clinics and tumor boards, establishing quality improvement initiatives, as well as developing procedural expertise.⁶

It is apparent that shared decision-making can become complex. These details will likely be lost to a primary care provider simply due to time constraints and information overload. As such, pulmonologists should be at the forefront of lung cancer screening – in programmatic development, implementation, and providing education to providers directly involved with shared decision-making discussions.
 

Dr. Aboudara is with the Division of Allergy, Pulmonary, and Critical Care; Vanderbilt University Medical Center; Nashville, Tennessee.

References

1. Huo J, Xu Y, Sheu T, et al. Complication rates and downstream medical costs associated with invasive diagnostic procedures for lung abnormalities in the community setting: Complications and medical costs associated with diagnostic procedures for lung abnormalities. JAMA Intern Med. 2019;179:324-32.

2. Folch EE, Pritchett MA, Nead MA, et al. Electromagnetic navigation bronchoscopy for peripheral pulmonary lesions: One-year results of the prospective, multicenter NAVIGATE study. J Thorac Oncol. 2019;14(3):445-58.

3. Ohno Y, Hatabu H, Takenaka D, et al. CT-guided transthoracic needle aspiration biopsy of small (< or = 20 mm) solitary pulmonary nodules. AJR Am J Roentgenol. 2003;180(6):1665-69.

4. Fukui M, Suzuki K, Matsunaga T, et al. Importance of smoking cessation on surgical outcome in primary lung cancer. Ann Thorac Surg. 2019;107(4):1005-09.

5. Mahajan A, Khandhar S, Folch EE. Pulmonary Perspectives^®: Ensuring quality for EBUS bronchoscopy with varying levels of practitioner experience. CHEST Physician. April 6, 2017. https://tinyurl.com/y3hwlc4g. .

6. Mullon JJ, Burkart KM, Silvestri G, et al. Interventional Pulmonology Fellowship Accreditation Standards: Executive summary of the Multisociety Interventional Pulmonology Fellowship Accreditation Committee. Chest. 2017;151(5):1114-21.

In a study highlighted in a recent issue of CHEST Physician, Hou and colleagues analyzed complications from biopsies of lung abnormalities seen on CT scans by conducting a large retrospective study with data gleaned from national databases of patients undergoing CT- guided biopsy, surgery, or bronchoscopy.¹ While it should not be interpreted as representative of a lung cancer screening population (for excellent comments by Drs. Rivera and Silvestri regarding the study, see: https://tinyurl.com/y52ucb94), it does raises two important questions when performing shared decision-making for low dose CT (LDCT) scanning: (1) What information should clinicians discuss with patients regarding various biopsy methods until more data are available? (2) How do we mitigate complications from biopsies?

While procedure-specific biopsy risk may be generalizable, it may be institutionally specific, and knowledge of local skill and outcomes data can help guide discussions. With that said, some general information can inform decisions. The NAVIGATE study investigators recently published their 1-year follow-up results using a navigational bronchoscopy system (superDimension^™). While inherent limitations to this study exist, it does provide some useful information as to procedure-related complications from a large sample of patients who approximate a lung cancer screening population. This group was composed of both academic and community centers and prospectively followed 1,215 patients for 1 year.² The average age of the population was 67.6 (± 11.3), and 80% were current or former smokers. The median nodule size was 2 cm. The diagnostic yield was 73% at 1 year follow-up (data will be re-analyzed at 2 years). The pneumothorax rate was 4%, with 3% requiring chest tube. Hemorrhage occurred in 2.5% of all patients, with 1.5% having a common terminology criteria for adverse events (CTCAE) ≥ 2. Grade 4 respiratory failure occurred in 1 patient. There were no ENB procedure-related deaths. It should be noted that individuals performing these procedures were, by and large, high-volume and experienced users.

In comparison, the overall pooled sensitivity for CT scan-guided biopsy is 90% for pulmonary nodules and masses. The yield is lower, however, for smaller lesions (≤2.0) and ranges from 74% to 77%.³ The average pneumothorax rate is 20%, with 1% to 3% requiring chest tube placement. Risk factors for pneumothorax vary between studies, but, generally speaking, have been associated with nodules ≤ 2 cm, those within 2 cm of the pleura (but not abutting the pleura), and emphysema in the track of needle trajectory. Pulmonary hemorrhage occurs 30% of the time but is mild in most cases. Hemoptysis and severe hemorrhage occur at rates of 4% and <1%, respectively. Risk factors for development of pulmonary hemorrhage include small lesion size (< 2 cm) and lesions > 2 cm from the pleura.

When considering surgical lung biopsies and resection, recent data suggest every effort should be made to encourage smoking cessation in order to mitigate postoperative morbidity. In a retrospective study by Fukui and colleagues,⁴ respiratory morbidity (defined as hypoxia, pneumonia, atelectasis, and uncontrolled sputum production) was 22% in smokers vs 3.5% in never smokers. The rate of complications decreased as the time from smoking cessation to date of surgery increased.

The goal for each patient who is counseled should be to limit the number of procedures and achieve the greatest diagnostic confidence with the lowest complication rate. With these risks and diagnostic yield in mind, the decision to recommend a particular biopsy strategy (or no biopsy at all) should be based on current guideline recommendations: (1) patient co-morbidities and preferences; (2) size of index nodule or mass; (3) presence of pathologically enlarged mediastinal and/or hilar lymphadenopathy; (4) evidence of extrathoracic metastasis; and (5) institutional expertise. Specifically speaking for the pulmonologist, this translates into identifying specific procedural “champions” who are dedicated to performing these procedures and are members of a multidisciplinary thoracic team. These individuals should have dedicated training in advanced diagnostic procedures to achieve the aforementioned goals.⁵ The same should hold true for transthoracic, CT-guided biopsies. Interventional pulmonology fellowships are structured to provide exposure to multidisciplinary nodule clinics and tumor boards, establishing quality improvement initiatives, as well as developing procedural expertise.⁶

It is apparent that shared decision-making can become complex. These details will likely be lost to a primary care provider simply due to time constraints and information overload. As such, pulmonologists should be at the forefront of lung cancer screening – in programmatic development, implementation, and providing education to providers directly involved with shared decision-making discussions.
 

Dr. Aboudara is with the Division of Allergy, Pulmonary, and Critical Care; Vanderbilt University Medical Center; Nashville, Tennessee.

References

1. Huo J, Xu Y, Sheu T, et al. Complication rates and downstream medical costs associated with invasive diagnostic procedures for lung abnormalities in the community setting: Complications and medical costs associated with diagnostic procedures for lung abnormalities. JAMA Intern Med. 2019;179:324-32.

2. Folch EE, Pritchett MA, Nead MA, et al. Electromagnetic navigation bronchoscopy for peripheral pulmonary lesions: One-year results of the prospective, multicenter NAVIGATE study. J Thorac Oncol. 2019;14(3):445-58.

3. Ohno Y, Hatabu H, Takenaka D, et al. CT-guided transthoracic needle aspiration biopsy of small (< or = 20 mm) solitary pulmonary nodules. AJR Am J Roentgenol. 2003;180(6):1665-69.

4. Fukui M, Suzuki K, Matsunaga T, et al. Importance of smoking cessation on surgical outcome in primary lung cancer. Ann Thorac Surg. 2019;107(4):1005-09.

5. Mahajan A, Khandhar S, Folch EE. Pulmonary Perspectives^®: Ensuring quality for EBUS bronchoscopy with varying levels of practitioner experience. CHEST Physician. April 6, 2017. https://tinyurl.com/y3hwlc4g. .

6. Mullon JJ, Burkart KM, Silvestri G, et al. Interventional Pulmonology Fellowship Accreditation Standards: Executive summary of the Multisociety Interventional Pulmonology Fellowship Accreditation Committee. Chest. 2017;151(5):1114-21.

In a study highlighted in a recent issue of CHEST Physician, Hou and colleagues analyzed complications from biopsies of lung abnormalities seen on CT scans by conducting a large retrospective study with data gleaned from national databases of patients undergoing CT- guided biopsy, surgery, or bronchoscopy.¹ While it should not be interpreted as representative of a lung cancer screening population (for excellent comments by Drs. Rivera and Silvestri regarding the study, see: https://tinyurl.com/y52ucb94), it does raises two important questions when performing shared decision-making for low dose CT (LDCT) scanning: (1) What information should clinicians discuss with patients regarding various biopsy methods until more data are available? (2) How do we mitigate complications from biopsies?

While procedure-specific biopsy risk may be generalizable, it may be institutionally specific, and knowledge of local skill and outcomes data can help guide discussions. With that said, some general information can inform decisions. The NAVIGATE study investigators recently published their 1-year follow-up results using a navigational bronchoscopy system (superDimension^™). While inherent limitations to this study exist, it does provide some useful information as to procedure-related complications from a large sample of patients who approximate a lung cancer screening population. This group was composed of both academic and community centers and prospectively followed 1,215 patients for 1 year.² The average age of the population was 67.6 (± 11.3), and 80% were current or former smokers. The median nodule size was 2 cm. The diagnostic yield was 73% at 1 year follow-up (data will be re-analyzed at 2 years). The pneumothorax rate was 4%, with 3% requiring chest tube. Hemorrhage occurred in 2.5% of all patients, with 1.5% having a common terminology criteria for adverse events (CTCAE) ≥ 2. Grade 4 respiratory failure occurred in 1 patient. There were no ENB procedure-related deaths. It should be noted that individuals performing these procedures were, by and large, high-volume and experienced users.

In comparison, the overall pooled sensitivity for CT scan-guided biopsy is 90% for pulmonary nodules and masses. The yield is lower, however, for smaller lesions (≤2.0) and ranges from 74% to 77%.³ The average pneumothorax rate is 20%, with 1% to 3% requiring chest tube placement. Risk factors for pneumothorax vary between studies, but, generally speaking, have been associated with nodules ≤ 2 cm, those within 2 cm of the pleura (but not abutting the pleura), and emphysema in the track of needle trajectory. Pulmonary hemorrhage occurs 30% of the time but is mild in most cases. Hemoptysis and severe hemorrhage occur at rates of 4% and <1%, respectively. Risk factors for development of pulmonary hemorrhage include small lesion size (< 2 cm) and lesions > 2 cm from the pleura.

When considering surgical lung biopsies and resection, recent data suggest every effort should be made to encourage smoking cessation in order to mitigate postoperative morbidity. In a retrospective study by Fukui and colleagues,⁴ respiratory morbidity (defined as hypoxia, pneumonia, atelectasis, and uncontrolled sputum production) was 22% in smokers vs 3.5% in never smokers. The rate of complications decreased as the time from smoking cessation to date of surgery increased.

The goal for each patient who is counseled should be to limit the number of procedures and achieve the greatest diagnostic confidence with the lowest complication rate. With these risks and diagnostic yield in mind, the decision to recommend a particular biopsy strategy (or no biopsy at all) should be based on current guideline recommendations: (1) patient co-morbidities and preferences; (2) size of index nodule or mass; (3) presence of pathologically enlarged mediastinal and/or hilar lymphadenopathy; (4) evidence of extrathoracic metastasis; and (5) institutional expertise. Specifically speaking for the pulmonologist, this translates into identifying specific procedural “champions” who are dedicated to performing these procedures and are members of a multidisciplinary thoracic team. These individuals should have dedicated training in advanced diagnostic procedures to achieve the aforementioned goals.⁵ The same should hold true for transthoracic, CT-guided biopsies. Interventional pulmonology fellowships are structured to provide exposure to multidisciplinary nodule clinics and tumor boards, establishing quality improvement initiatives, as well as developing procedural expertise.⁶

It is apparent that shared decision-making can become complex. These details will likely be lost to a primary care provider simply due to time constraints and information overload. As such, pulmonologists should be at the forefront of lung cancer screening – in programmatic development, implementation, and providing education to providers directly involved with shared decision-making discussions.
 

Dr. Aboudara is with the Division of Allergy, Pulmonary, and Critical Care; Vanderbilt University Medical Center; Nashville, Tennessee.

References

1. Huo J, Xu Y, Sheu T, et al. Complication rates and downstream medical costs associated with invasive diagnostic procedures for lung abnormalities in the community setting: Complications and medical costs associated with diagnostic procedures for lung abnormalities. JAMA Intern Med. 2019;179:324-32.

2. Folch EE, Pritchett MA, Nead MA, et al. Electromagnetic navigation bronchoscopy for peripheral pulmonary lesions: One-year results of the prospective, multicenter NAVIGATE study. J Thorac Oncol. 2019;14(3):445-58.

3. Ohno Y, Hatabu H, Takenaka D, et al. CT-guided transthoracic needle aspiration biopsy of small (< or = 20 mm) solitary pulmonary nodules. AJR Am J Roentgenol. 2003;180(6):1665-69.

4. Fukui M, Suzuki K, Matsunaga T, et al. Importance of smoking cessation on surgical outcome in primary lung cancer. Ann Thorac Surg. 2019;107(4):1005-09.

5. Mahajan A, Khandhar S, Folch EE. Pulmonary Perspectives^®: Ensuring quality for EBUS bronchoscopy with varying levels of practitioner experience. CHEST Physician. April 6, 2017. https://tinyurl.com/y3hwlc4g. .

6. Mullon JJ, Burkart KM, Silvestri G, et al. Interventional Pulmonology Fellowship Accreditation Standards: Executive summary of the Multisociety Interventional Pulmonology Fellowship Accreditation Committee. Chest. 2017;151(5):1114-21.

The global burden COPD is considerable. In the United States, it is the third most common cause of death and is associated with over $50 billion in annual direct and indirect health-care expenditures (Guarascio AJ, et al. Clinicoecon Outcomes Res. 2013;5:235). For patients with severe emphysema with hyperinflation, dyspnea is often a quality of life (QOL)-limiting symptom (O’Donnell DE, et al. Ann Am Thorac Soc. 2017;14:S30). Few proven palliation options exist, particularly for patients with dyspnea refractory to smoking cessation, medical management with bronchodilators, and pulmonary rehabilitation. The recent Food and Drug Administration (FDA) approval of two endobronchial valves for lung volume reduction has established the increasing importance of bronchoscopy as a management tool in advanced COPD.
 

Why were these valves developed?

Courtesy of Dr. Catherine L. Oberg

For decades, lung volume reduction has been investigated as a mechanical approach to counter-act the physiologic effects of emphysematous hyperinflation. Its goal is to improve lung elastic recoil, respiratory muscle mechanical advantage and efficiency, and ventilation/perfusion matching. The landmark National Emphysema Treatment Trial (NETT), published in 2001 and 2003, demonstrated that in a select patient population (upper lobe-predominant emphysema and low exercise capacity), lung volume reduction surgery (LVRS) lowers mortality and improves QOL and exercise tolerance (Fishman A et al. N Engl J Med. 2003;348:2059). Despite the encouraging results in this study subpopulation, LVRS is per-formed infrequently (Decker MR, et al. J Thorac Cardiovasc Surg. 2014;148:2651). Concern about its morbidity and the specialized nature of the procedure has hindered widespread adoption. Subsequently, endobronchial techniques have been developed as an alternative to surgical lung volume reduction.
 

How does bronchoscopic lung volume reduction (BLVR) benefit patients with emphysema?

Courtesy of Dr. Catherine L. Oberg

Valves used for ELVR are removable one-way flow devices placed by flexible bronchoscopy into selected airways supplying emphysematous lung. The valves block air entry but allow the exit of secretions and trapped air. This results in atelectasis of the targeted lobe and a decrease in lung volume.
 

Which endobronchial valves are available in the United States?

In 2018, two valves were approved by the FDA for bronchoscopic lung volume reduction (BLVR) – the Zephyr^® EBV (Pulmonx) ( (Fig 1) and the Spiration^® Valve System (Olympus) (IBV) (Fig 2). The Zephyr^® EBV is a duckbill-shaped silicone valve mounted within a self-expanding nitinol (nickel titanium alloy) stent. It comes in three sizes for airways with a diameter 4 - 8.5 mm. The Spiration^® IBV umbrella-shaped valve is com-posed of six nitinol struts surfaced with polyurethane. Its four sizes accommodate airway diameters 5 - 9 mm.
 

What’s the evidence behind BLVR?

Zephyr^® Valves

The Endobronchial Valve for Emphysema Palliation Trial (VENT), the largest valve trial thus far, randomized patients with severe heterogeneous emphysema to receive unilateral Zephyr^® valve placement or standard medical care (Sciurba FC, et al. N Engl J Med. 2010;363:1233). Overall improvement in spirometry and dyspnea scores was modest in the valve group. Post-hoc analysis identified an important subgroup of patients with significant clinical benefit, those with a complete fissure. This finding gave guidance to further EBV studies on patients with severe emphysema and absent collateral ventilation (CV).

Identifying a complete fissure on imaging is now used as a surrogate for assessing CV and is an integral part of the initial profiling of patients for EBV therapy (Koster TD, et al. Respiration. 2016;92(3):150).

In the STELVIO trial, 68 patients were randomized to Zephyr ® EBV placement or standard medical care (Klooster K, et al. N Engl J Med. 2015;373:2325). Those with EBV placement had significantly improved lung function and exercise capacity. TRANSFORM, a multicenter trial evaluating Zephyr^® EBV placement in heterogeneous emphysema, showed similar results (Kemp SV, et al. Am J Respir Crit Care Med. 2017;196:1535).

The IMPACT trial compared patients with homogenous emphysema without CV to standard medical therapy alone. It showed improvement in FEV1, QOL scores, and exercise tolerance in the EBV group. This study affirmed that the absence of CV, rather than the pattern of emphysema, correlates with the clinical benefit from EBV therapy (Valipour A, et al. Am J Respir Crit Care Med. 2016;194(9):1073). Finally, LIBERATE, a multicenter study on the Zephyr^® EBV, examined its placement in patients with heterogenous emphysema. This study demonstrated improvement in spirometry, QOL, and 6-minute walk test (6-MWT) distance (Criner GJ, et al. Am J Respir Crit Care Med. 2018;198:1151) over a longer period, 12 months, bolstering the findings of prior studies. These results prompted the Zephyr^® valve’s FDA approval.
 

Spiration^® Valves

Small trials have shown favorable results with the Spiration^® IBV for BLVR, including a pilot multicenter cohort study of 30 patients with heterogeneous, upper-lobe emphysema who underwent valve placement (Wood DE, et al. J Thorac Cardiovasc Surg. 2007;133:65). In this trial, investigators found significant improvement in QOL scores, but no change in FEV₁ or other physiologic parameters.

The EMPROVE trial is a multicenter, prospective, randomized, controlled study assessing BLVR with the Spiration^® IBV. Six- and twelve-month data from the trial were presented in 2018 at the American Thoracic Society Conference and at the European Respiratory Society International Conference.
 

Collateral Ventilation

Identifying patients in whom there is no CV between lobes is critical to success with BLVR. Collateral ventilation allows air to bypass the valve occlusion distally, thereby negating the desired effect of valve placement, lobar atelectasis. High-resolution computed tomography (HRCT) scanning combined with quantitative software can be used to assess emphysema distribution and fissure integrity. Additionally, a proprietary technology, the Chartis System^®, can be employed intra-procedure to estimate CV by measuring airway flow, resistance, and pressure in targeted balloon-occluded segments. Absence of CV based on Chartis evaluation was an inclusion criterion in the aforementioned valve studies.

Which patients with emphysema should be referred for consideration of valve placement?

The following criteria should be used in selecting patients for referral for BLVR:

• FEV₁ 15% - 45% of predicted value at baseline

• Evidence of hyperinflation: TLC greater than or equal to 100% and RV greater than or equal to 175%

• Baseline postpulmonary rehabilitation 6-MWT distance of 100 - 500 meters

• Clinically stable on < 20 mg prednisone (or equivalent) daily

• Nonsmoking for at least 4 months

• Integrity of one or both major fissures at least 75%

• Ability to provide informed consent and to tolerate bronchoscopy
 

Complications

The most common complication after valve placement is pneumothorax – a double-edged sword in that it typically indicates the achievement of atelectasis. In published trials, the frequency of pneumothorax varies. Some studies document rates below 10%. Others report rates of nearly 30% (Gompelmann D, et al. Respiration. 2014;87:485). In landmark trials, death related to pneumothorax occurred rarely. Most severe pneumothoraces occur within the first 72 hours after valve placement. This has prompted many centers to observe postprocedure patients in hospital for an extended period. Pneumonia and COPD exacerbations have also been reported after EBV placement. Therefore, in some trials, patients received prophylactic prednisolone and azithromycin. Other less common complications are hemoptysis, granulation tissue formation, and valve migration.


 

What’s ahead for ELVR?

Overall, valve technology for BLVR is an exciting option in the management of patients with severe emphysema and is now a staple for any advanced emphysema program. Key areas of future interest include management of patients with partial fissures, minimizing adverse procedural effects, and developing programs to optimize and streamline a multidisciplinary approach to timely and efficient referral, assessment, and intervention. As more patients with COPD undergo ELVR, one goal should be to create multi-institution prospective studies as well as registries to delineate further the optimal use of endobronchial valves for lung volume reduction.



Zephyr^® Endobronchial Valve (Pulmonx)

Spiration^® Valve System (Olympus)

The American College of Chest Physicians (CHEST) does not endorse or supp


 

The global burden COPD is considerable. In the United States, it is the third most common cause of death and is associated with over $50 billion in annual direct and indirect health-care expenditures (Guarascio AJ, et al. Clinicoecon Outcomes Res. 2013;5:235). For patients with severe emphysema with hyperinflation, dyspnea is often a quality of life (QOL)-limiting symptom (O’Donnell DE, et al. Ann Am Thorac Soc. 2017;14:S30). Few proven palliation options exist, particularly for patients with dyspnea refractory to smoking cessation, medical management with bronchodilators, and pulmonary rehabilitation. The recent Food and Drug Administration (FDA) approval of two endobronchial valves for lung volume reduction has established the increasing importance of bronchoscopy as a management tool in advanced COPD.
 

Why were these valves developed?

Courtesy of Dr. Catherine L. Oberg

For decades, lung volume reduction has been investigated as a mechanical approach to counter-act the physiologic effects of emphysematous hyperinflation. Its goal is to improve lung elastic recoil, respiratory muscle mechanical advantage and efficiency, and ventilation/perfusion matching. The landmark National Emphysema Treatment Trial (NETT), published in 2001 and 2003, demonstrated that in a select patient population (upper lobe-predominant emphysema and low exercise capacity), lung volume reduction surgery (LVRS) lowers mortality and improves QOL and exercise tolerance (Fishman A et al. N Engl J Med. 2003;348:2059). Despite the encouraging results in this study subpopulation, LVRS is per-formed infrequently (Decker MR, et al. J Thorac Cardiovasc Surg. 2014;148:2651). Concern about its morbidity and the specialized nature of the procedure has hindered widespread adoption. Subsequently, endobronchial techniques have been developed as an alternative to surgical lung volume reduction.
 

How does bronchoscopic lung volume reduction (BLVR) benefit patients with emphysema?

Courtesy of Dr. Catherine L. Oberg

Valves used for ELVR are removable one-way flow devices placed by flexible bronchoscopy into selected airways supplying emphysematous lung. The valves block air entry but allow the exit of secretions and trapped air. This results in atelectasis of the targeted lobe and a decrease in lung volume.
 

Which endobronchial valves are available in the United States?

In 2018, two valves were approved by the FDA for bronchoscopic lung volume reduction (BLVR) – the Zephyr^® EBV (Pulmonx) ( (Fig 1) and the Spiration^® Valve System (Olympus) (IBV) (Fig 2). The Zephyr^® EBV is a duckbill-shaped silicone valve mounted within a self-expanding nitinol (nickel titanium alloy) stent. It comes in three sizes for airways with a diameter 4 - 8.5 mm. The Spiration^® IBV umbrella-shaped valve is com-posed of six nitinol struts surfaced with polyurethane. Its four sizes accommodate airway diameters 5 - 9 mm.
 

What’s the evidence behind BLVR?

Zephyr^® Valves

The Endobronchial Valve for Emphysema Palliation Trial (VENT), the largest valve trial thus far, randomized patients with severe heterogeneous emphysema to receive unilateral Zephyr^® valve placement or standard medical care (Sciurba FC, et al. N Engl J Med. 2010;363:1233). Overall improvement in spirometry and dyspnea scores was modest in the valve group. Post-hoc analysis identified an important subgroup of patients with significant clinical benefit, those with a complete fissure. This finding gave guidance to further EBV studies on patients with severe emphysema and absent collateral ventilation (CV).

Identifying a complete fissure on imaging is now used as a surrogate for assessing CV and is an integral part of the initial profiling of patients for EBV therapy (Koster TD, et al. Respiration. 2016;92(3):150).

In the STELVIO trial, 68 patients were randomized to Zephyr ® EBV placement or standard medical care (Klooster K, et al. N Engl J Med. 2015;373:2325). Those with EBV placement had significantly improved lung function and exercise capacity. TRANSFORM, a multicenter trial evaluating Zephyr^® EBV placement in heterogeneous emphysema, showed similar results (Kemp SV, et al. Am J Respir Crit Care Med. 2017;196:1535).

The IMPACT trial compared patients with homogenous emphysema without CV to standard medical therapy alone. It showed improvement in FEV1, QOL scores, and exercise tolerance in the EBV group. This study affirmed that the absence of CV, rather than the pattern of emphysema, correlates with the clinical benefit from EBV therapy (Valipour A, et al. Am J Respir Crit Care Med. 2016;194(9):1073). Finally, LIBERATE, a multicenter study on the Zephyr^® EBV, examined its placement in patients with heterogenous emphysema. This study demonstrated improvement in spirometry, QOL, and 6-minute walk test (6-MWT) distance (Criner GJ, et al. Am J Respir Crit Care Med. 2018;198:1151) over a longer period, 12 months, bolstering the findings of prior studies. These results prompted the Zephyr^® valve’s FDA approval.
 

Spiration^® Valves

Small trials have shown favorable results with the Spiration^® IBV for BLVR, including a pilot multicenter cohort study of 30 patients with heterogeneous, upper-lobe emphysema who underwent valve placement (Wood DE, et al. J Thorac Cardiovasc Surg. 2007;133:65). In this trial, investigators found significant improvement in QOL scores, but no change in FEV₁ or other physiologic parameters.

The EMPROVE trial is a multicenter, prospective, randomized, controlled study assessing BLVR with the Spiration^® IBV. Six- and twelve-month data from the trial were presented in 2018 at the American Thoracic Society Conference and at the European Respiratory Society International Conference.
 

Collateral Ventilation

Identifying patients in whom there is no CV between lobes is critical to success with BLVR. Collateral ventilation allows air to bypass the valve occlusion distally, thereby negating the desired effect of valve placement, lobar atelectasis. High-resolution computed tomography (HRCT) scanning combined with quantitative software can be used to assess emphysema distribution and fissure integrity. Additionally, a proprietary technology, the Chartis System^®, can be employed intra-procedure to estimate CV by measuring airway flow, resistance, and pressure in targeted balloon-occluded segments. Absence of CV based on Chartis evaluation was an inclusion criterion in the aforementioned valve studies.

Which patients with emphysema should be referred for consideration of valve placement?

The following criteria should be used in selecting patients for referral for BLVR:

• FEV₁ 15% - 45% of predicted value at baseline

• Evidence of hyperinflation: TLC greater than or equal to 100% and RV greater than or equal to 175%

• Baseline postpulmonary rehabilitation 6-MWT distance of 100 - 500 meters

• Clinically stable on < 20 mg prednisone (or equivalent) daily

• Nonsmoking for at least 4 months

• Integrity of one or both major fissures at least 75%

• Ability to provide informed consent and to tolerate bronchoscopy
 

Complications

The most common complication after valve placement is pneumothorax – a double-edged sword in that it typically indicates the achievement of atelectasis. In published trials, the frequency of pneumothorax varies. Some studies document rates below 10%. Others report rates of nearly 30% (Gompelmann D, et al. Respiration. 2014;87:485). In landmark trials, death related to pneumothorax occurred rarely. Most severe pneumothoraces occur within the first 72 hours after valve placement. This has prompted many centers to observe postprocedure patients in hospital for an extended period. Pneumonia and COPD exacerbations have also been reported after EBV placement. Therefore, in some trials, patients received prophylactic prednisolone and azithromycin. Other less common complications are hemoptysis, granulation tissue formation, and valve migration.


 

What’s ahead for ELVR?

Overall, valve technology for BLVR is an exciting option in the management of patients with severe emphysema and is now a staple for any advanced emphysema program. Key areas of future interest include management of patients with partial fissures, minimizing adverse procedural effects, and developing programs to optimize and streamline a multidisciplinary approach to timely and efficient referral, assessment, and intervention. As more patients with COPD undergo ELVR, one goal should be to create multi-institution prospective studies as well as registries to delineate further the optimal use of endobronchial valves for lung volume reduction.



Zephyr^® Endobronchial Valve (Pulmonx)

Spiration^® Valve System (Olympus)

The American College of Chest Physicians (CHEST) does not endorse or supp


 

The global burden COPD is considerable. In the United States, it is the third most common cause of death and is associated with over $50 billion in annual direct and indirect health-care expenditures (Guarascio AJ, et al. Clinicoecon Outcomes Res. 2013;5:235). For patients with severe emphysema with hyperinflation, dyspnea is often a quality of life (QOL)-limiting symptom (O’Donnell DE, et al. Ann Am Thorac Soc. 2017;14:S30). Few proven palliation options exist, particularly for patients with dyspnea refractory to smoking cessation, medical management with bronchodilators, and pulmonary rehabilitation. The recent Food and Drug Administration (FDA) approval of two endobronchial valves for lung volume reduction has established the increasing importance of bronchoscopy as a management tool in advanced COPD.
 

Why were these valves developed?

Courtesy of Dr. Catherine L. Oberg

For decades, lung volume reduction has been investigated as a mechanical approach to counter-act the physiologic effects of emphysematous hyperinflation. Its goal is to improve lung elastic recoil, respiratory muscle mechanical advantage and efficiency, and ventilation/perfusion matching. The landmark National Emphysema Treatment Trial (NETT), published in 2001 and 2003, demonstrated that in a select patient population (upper lobe-predominant emphysema and low exercise capacity), lung volume reduction surgery (LVRS) lowers mortality and improves QOL and exercise tolerance (Fishman A et al. N Engl J Med. 2003;348:2059). Despite the encouraging results in this study subpopulation, LVRS is per-formed infrequently (Decker MR, et al. J Thorac Cardiovasc Surg. 2014;148:2651). Concern about its morbidity and the specialized nature of the procedure has hindered widespread adoption. Subsequently, endobronchial techniques have been developed as an alternative to surgical lung volume reduction.
 

How does bronchoscopic lung volume reduction (BLVR) benefit patients with emphysema?

Courtesy of Dr. Catherine L. Oberg

Valves used for ELVR are removable one-way flow devices placed by flexible bronchoscopy into selected airways supplying emphysematous lung. The valves block air entry but allow the exit of secretions and trapped air. This results in atelectasis of the targeted lobe and a decrease in lung volume.
 

Which endobronchial valves are available in the United States?

In 2018, two valves were approved by the FDA for bronchoscopic lung volume reduction (BLVR) – the Zephyr^® EBV (Pulmonx) ( (Fig 1) and the Spiration^® Valve System (Olympus) (IBV) (Fig 2). The Zephyr^® EBV is a duckbill-shaped silicone valve mounted within a self-expanding nitinol (nickel titanium alloy) stent. It comes in three sizes for airways with a diameter 4 - 8.5 mm. The Spiration^® IBV umbrella-shaped valve is com-posed of six nitinol struts surfaced with polyurethane. Its four sizes accommodate airway diameters 5 - 9 mm.
 

What’s the evidence behind BLVR?

Zephyr^® Valves

The Endobronchial Valve for Emphysema Palliation Trial (VENT), the largest valve trial thus far, randomized patients with severe heterogeneous emphysema to receive unilateral Zephyr^® valve placement or standard medical care (Sciurba FC, et al. N Engl J Med. 2010;363:1233). Overall improvement in spirometry and dyspnea scores was modest in the valve group. Post-hoc analysis identified an important subgroup of patients with significant clinical benefit, those with a complete fissure. This finding gave guidance to further EBV studies on patients with severe emphysema and absent collateral ventilation (CV).

Identifying a complete fissure on imaging is now used as a surrogate for assessing CV and is an integral part of the initial profiling of patients for EBV therapy (Koster TD, et al. Respiration. 2016;92(3):150).

In the STELVIO trial, 68 patients were randomized to Zephyr ® EBV placement or standard medical care (Klooster K, et al. N Engl J Med. 2015;373:2325). Those with EBV placement had significantly improved lung function and exercise capacity. TRANSFORM, a multicenter trial evaluating Zephyr^® EBV placement in heterogeneous emphysema, showed similar results (Kemp SV, et al. Am J Respir Crit Care Med. 2017;196:1535).

The IMPACT trial compared patients with homogenous emphysema without CV to standard medical therapy alone. It showed improvement in FEV1, QOL scores, and exercise tolerance in the EBV group. This study affirmed that the absence of CV, rather than the pattern of emphysema, correlates with the clinical benefit from EBV therapy (Valipour A, et al. Am J Respir Crit Care Med. 2016;194(9):1073). Finally, LIBERATE, a multicenter study on the Zephyr^® EBV, examined its placement in patients with heterogenous emphysema. This study demonstrated improvement in spirometry, QOL, and 6-minute walk test (6-MWT) distance (Criner GJ, et al. Am J Respir Crit Care Med. 2018;198:1151) over a longer period, 12 months, bolstering the findings of prior studies. These results prompted the Zephyr^® valve’s FDA approval.
 

Spiration^® Valves

Small trials have shown favorable results with the Spiration^® IBV for BLVR, including a pilot multicenter cohort study of 30 patients with heterogeneous, upper-lobe emphysema who underwent valve placement (Wood DE, et al. J Thorac Cardiovasc Surg. 2007;133:65). In this trial, investigators found significant improvement in QOL scores, but no change in FEV₁ or other physiologic parameters.

The EMPROVE trial is a multicenter, prospective, randomized, controlled study assessing BLVR with the Spiration^® IBV. Six- and twelve-month data from the trial were presented in 2018 at the American Thoracic Society Conference and at the European Respiratory Society International Conference.
 

Collateral Ventilation

Identifying patients in whom there is no CV between lobes is critical to success with BLVR. Collateral ventilation allows air to bypass the valve occlusion distally, thereby negating the desired effect of valve placement, lobar atelectasis. High-resolution computed tomography (HRCT) scanning combined with quantitative software can be used to assess emphysema distribution and fissure integrity. Additionally, a proprietary technology, the Chartis System^®, can be employed intra-procedure to estimate CV by measuring airway flow, resistance, and pressure in targeted balloon-occluded segments. Absence of CV based on Chartis evaluation was an inclusion criterion in the aforementioned valve studies.

Which patients with emphysema should be referred for consideration of valve placement?

The following criteria should be used in selecting patients for referral for BLVR:

• FEV₁ 15% - 45% of predicted value at baseline

• Evidence of hyperinflation: TLC greater than or equal to 100% and RV greater than or equal to 175%

• Baseline postpulmonary rehabilitation 6-MWT distance of 100 - 500 meters

• Clinically stable on < 20 mg prednisone (or equivalent) daily

• Nonsmoking for at least 4 months

• Integrity of one or both major fissures at least 75%

• Ability to provide informed consent and to tolerate bronchoscopy
 

Complications

The most common complication after valve placement is pneumothorax – a double-edged sword in that it typically indicates the achievement of atelectasis. In published trials, the frequency of pneumothorax varies. Some studies document rates below 10%. Others report rates of nearly 30% (Gompelmann D, et al. Respiration. 2014;87:485). In landmark trials, death related to pneumothorax occurred rarely. Most severe pneumothoraces occur within the first 72 hours after valve placement. This has prompted many centers to observe postprocedure patients in hospital for an extended period. Pneumonia and COPD exacerbations have also been reported after EBV placement. Therefore, in some trials, patients received prophylactic prednisolone and azithromycin. Other less common complications are hemoptysis, granulation tissue formation, and valve migration.


 

What’s ahead for ELVR?

Overall, valve technology for BLVR is an exciting option in the management of patients with severe emphysema and is now a staple for any advanced emphysema program. Key areas of future interest include management of patients with partial fissures, minimizing adverse procedural effects, and developing programs to optimize and streamline a multidisciplinary approach to timely and efficient referral, assessment, and intervention. As more patients with COPD undergo ELVR, one goal should be to create multi-institution prospective studies as well as registries to delineate further the optimal use of endobronchial valves for lung volume reduction.



Zephyr^® Endobronchial Valve (Pulmonx)

Spiration^® Valve System (Olympus)

The American College of Chest Physicians (CHEST) does not endorse or supp


 

Editor’s Picks


COMMENTARY
On Being the Editor in Chief of the Journal CHEST: 14 Memorable Years.
By Dr. Richard S. Irwin

ORIGINAL RESEARCH
Procalcitonin-Guided Antibiotic Discontinuation and Mortality in Critically Ill Adults: A Systematic Review and Meta-analysis.
By Dr. B. J. Pepper, et al.

A Novel Algorithm to Analyze Epidemiology and Outcomes of Carbapenem Resistance Among Patients With Hospital-Acquired and Ventilator-Associated Pneumonia: A Retrospective Cohort Study.
By Dr. M. D. Zilberberg, et al.

Raw Bioelectrical Impedance Analysis Variables Are Independent Predictors of Early All-Cause Mortality in Patients With COPD.
By Dr. Francesca de Blasio, et al.

Editor’s Picks


COMMENTARY
On Being the Editor in Chief of the Journal CHEST: 14 Memorable Years.
By Dr. Richard S. Irwin

ORIGINAL RESEARCH
Procalcitonin-Guided Antibiotic Discontinuation and Mortality in Critically Ill Adults: A Systematic Review and Meta-analysis.
By Dr. B. J. Pepper, et al.

A Novel Algorithm to Analyze Epidemiology and Outcomes of Carbapenem Resistance Among Patients With Hospital-Acquired and Ventilator-Associated Pneumonia: A Retrospective Cohort Study.
By Dr. M. D. Zilberberg, et al.

Raw Bioelectrical Impedance Analysis Variables Are Independent Predictors of Early All-Cause Mortality in Patients With COPD.
By Dr. Francesca de Blasio, et al.

Editor’s Picks


COMMENTARY
On Being the Editor in Chief of the Journal CHEST: 14 Memorable Years.
By Dr. Richard S. Irwin

ORIGINAL RESEARCH
Procalcitonin-Guided Antibiotic Discontinuation and Mortality in Critically Ill Adults: A Systematic Review and Meta-analysis.
By Dr. B. J. Pepper, et al.

A Novel Algorithm to Analyze Epidemiology and Outcomes of Carbapenem Resistance Among Patients With Hospital-Acquired and Ventilator-Associated Pneumonia: A Retrospective Cohort Study.
By Dr. M. D. Zilberberg, et al.

Raw Bioelectrical Impedance Analysis Variables Are Independent Predictors of Early All-Cause Mortality in Patients With COPD.
By Dr. Francesca de Blasio, et al.

Recently, the CHEST Foundation had the pleasure of sitting down with Salim Surani, MD, FCCP to get his perspective on the NetWorks Challenge and its impact. Dr. Surani initially got involved with CHEST at the Board level and is now a leader within the Council of NetWorks. “My hope was that I could work within my NetWork to help them become more involved with CHEST and the CHEST Foundation. Through this involvement, I believe we can help shape changes in chest medicine practice dynamics. In the Practice Operations NetWork, we strive to educate physicians in practice to ensure they are up to date with government regulations and how to navigate changes in a positive way, ultimately with the goal of impacting our patients’ lives for the better.”

When asked about his involvement with CHEST and the Foundation, he said “It just makes sense to be involved in an institution that is passionate about taking care of patients and clinicians. The CHEST Foundation has given tens of millions of dollars in funding for grants to help shape the future of the education, the future of research, and the future of better patient care.”

Dr. Surani has always been a strong advocate for the NetWorks Challenge. “There is nothing that has been more satisfying in my life than the opportunity to give. I have always believed that the biggest winner is the person who gives a gift. When you give something to the right cause, what you get in return is a tremendous amount of satisfaction, and it is that satisfaction which drives you – which gives you a feeling of purpose. I want others to get involved and participate. If you feel passionate about something, put your money where your mouth is. This is why I will be matching any gift of $500 or greater by 10% made to any NetWork during the NetWorks Challenge. This is an opportunity to multiply your donation before it goes to the CHEST Foundation so that grants and other awards can be larger in the coming years. The NetWorks Challenge helps fund our Diversity Travel Grants Program and provides additional travel grants to each participating NetWork.” Last year, Dr. Surani gave an additional $2,365.17 through his challenge match. Are you up for the challenge this year?

Visit chestfoundation.org/donate today to help shape the future of our discipline!

Recently, the CHEST Foundation had the pleasure of sitting down with Salim Surani, MD, FCCP to get his perspective on the NetWorks Challenge and its impact. Dr. Surani initially got involved with CHEST at the Board level and is now a leader within the Council of NetWorks. “My hope was that I could work within my NetWork to help them become more involved with CHEST and the CHEST Foundation. Through this involvement, I believe we can help shape changes in chest medicine practice dynamics. In the Practice Operations NetWork, we strive to educate physicians in practice to ensure they are up to date with government regulations and how to navigate changes in a positive way, ultimately with the goal of impacting our patients’ lives for the better.”

When asked about his involvement with CHEST and the Foundation, he said “It just makes sense to be involved in an institution that is passionate about taking care of patients and clinicians. The CHEST Foundation has given tens of millions of dollars in funding for grants to help shape the future of the education, the future of research, and the future of better patient care.”

Dr. Surani has always been a strong advocate for the NetWorks Challenge. “There is nothing that has been more satisfying in my life than the opportunity to give. I have always believed that the biggest winner is the person who gives a gift. When you give something to the right cause, what you get in return is a tremendous amount of satisfaction, and it is that satisfaction which drives you – which gives you a feeling of purpose. I want others to get involved and participate. If you feel passionate about something, put your money where your mouth is. This is why I will be matching any gift of $500 or greater by 10% made to any NetWork during the NetWorks Challenge. This is an opportunity to multiply your donation before it goes to the CHEST Foundation so that grants and other awards can be larger in the coming years. The NetWorks Challenge helps fund our Diversity Travel Grants Program and provides additional travel grants to each participating NetWork.” Last year, Dr. Surani gave an additional $2,365.17 through his challenge match. Are you up for the challenge this year?

Visit chestfoundation.org/donate today to help shape the future of our discipline!

Recently, the CHEST Foundation had the pleasure of sitting down with Salim Surani, MD, FCCP to get his perspective on the NetWorks Challenge and its impact. Dr. Surani initially got involved with CHEST at the Board level and is now a leader within the Council of NetWorks. “My hope was that I could work within my NetWork to help them become more involved with CHEST and the CHEST Foundation. Through this involvement, I believe we can help shape changes in chest medicine practice dynamics. In the Practice Operations NetWork, we strive to educate physicians in practice to ensure they are up to date with government regulations and how to navigate changes in a positive way, ultimately with the goal of impacting our patients’ lives for the better.”

When asked about his involvement with CHEST and the Foundation, he said “It just makes sense to be involved in an institution that is passionate about taking care of patients and clinicians. The CHEST Foundation has given tens of millions of dollars in funding for grants to help shape the future of the education, the future of research, and the future of better patient care.”

Dr. Surani has always been a strong advocate for the NetWorks Challenge. “There is nothing that has been more satisfying in my life than the opportunity to give. I have always believed that the biggest winner is the person who gives a gift. When you give something to the right cause, what you get in return is a tremendous amount of satisfaction, and it is that satisfaction which drives you – which gives you a feeling of purpose. I want others to get involved and participate. If you feel passionate about something, put your money where your mouth is. This is why I will be matching any gift of $500 or greater by 10% made to any NetWork during the NetWorks Challenge. This is an opportunity to multiply your donation before it goes to the CHEST Foundation so that grants and other awards can be larger in the coming years. The NetWorks Challenge helps fund our Diversity Travel Grants Program and provides additional travel grants to each participating NetWork.” Last year, Dr. Surani gave an additional $2,365.17 through his challenge match. Are you up for the challenge this year?

Visit chestfoundation.org/donate today to help shape the future of our discipline!

Clinical Pulmonary Medicine

Pulmonary embolism in pregnancy: A diagnostic conundrum

Pulmonary embolism (PE) is the 6th leading cause of maternal mortality in the United States. The clinical signs and symptoms of PE are usually nonspecific and often overlap with the normal physiologic changes of pregnancy. Due to low specificity and sensitivity of D-dimer test, pregnant patients with suspected PE often undergo CT pulmonary angiography (CTPA) and ventilation-perfusion scanning, both of which can cause radiation exposure to mother and fetus.

To answer whether pregnancy-adapted YEARS algorithm (Van der Hulle T et al. Lancet. 2017;390[10091]:289) can be safely used to avoid diagnostic imaging, Artemis Study Investigators prospectively studied three criteria from YEARS algorithm in combination with a D-dimer level (Van der Pol et al. N Engl J Med. 2019;380[12]:1139. The three criteria included clinical signs of deep-vein thrombosis (DVT), hemoptysis, and PE as the most likely diagnosis. PE was considered ruled out when none of the three criteria were present and D-dimer was less than 1000 ng/mL or if one or more of the criteria were met and D-dimer was less than 500 ng/mL. Patients in whom D-dimer was greater than 1000 ng/mL or in those with D-dimer greater than 500 ng/mL and had 1 or more of the YEARS algorithm criteria present, PE could not be ruled out and underwent CTPA. A modification of the criteria was done only for patients who had clinical signs of DVT at baseline. These patients underwent compression ultrasonography and if a clot was found, CTPA was not performed and patients were started on anticoagulation therapy. Those with negative DVT studies were subclassified based on D-dimer levels as the study population above. Patients in whom pulmonary embolism was not ruled out underwent CTPA. Of these 299 patients, 16 (5.4%) were confirmed to have PE at baseline.

In the remaining 195 patients in whom PE was ruled out on the basis of study protocol, a 3-month follow-up diagnosed one patient (0.51%) with VTE. Using pregnancy-adapted YEARS algorithm, CTPA was avoided in 39% of the patients of which 65% were in their first trimester when the radiation exposure can be most harmful to the fetus.

Muhammad Adrish, MD, FCCP
Steering Committee Member

Munish Luthra, MD, FCCP
Steering Committee Member
 

Cardiovascular Medicine and Surgery

Physical examination of low cardiac output in the ICU

Regarding determination of shock etiology, in a small series of patients with systolic blood pressure < 90 mm Hg, physical exam findings of relatively warm skin temperature and rapid capillary refill had 89% sensitivity for vasodilatory shock, and jugular venous pressure ≥8 had 82% sensitivity for cardiogenic etiologies (Vazquez, et al. J Hosp Med. 2010;5[8]:471). Thus, while physical exam findings may inform bedside shock assessment, their accuracy is limited. Critical care physicians should consider additional assessment techniques, such as echocardiography or invasive hemodynamic monitoring, if diagnostic uncertainty persists (Vincent, et al. N Engl J Med. 2013;369[18]:1726).

Benjamin Kenigsberg, MD
Steering Committee Member

Dr. David Bowton and Dr. Steven Hollenberg contributed to the article.
 

Chest Infections

Lung infections in the transplant recipients

Multiple factors contribute to this increased infection risk, including donor lung colonization, disruption of local host defenses, constant contact with environmental pathogens, and heavy immunosuppression (Redmund KF, et al. Proc Am Thorac Soc. 2009;6[1]:94).

The onset of infectious manifestations, from the time of transplantation, is variable, depending on the organism. Based on the time of onset, infections can be categorized into within the first month posttransplant, 1 to 6 months, and beyond 6 months, posttransplant. During the first month, because of allograft colonization, preexisting infections in the recipient, and surgical- and hospital-acquired nosocomial infections are more common. The first 6 months are where the patients are at the highest risk for opportunistic infections. As the immunosuppression is lowered after 6 months, the causative organisms tend to be more common pathogens (Green M. Am J Transplant. 2013;13 [suppl 4]:3-8).

An early, aggressive, empiric antimicrobial therapy initiation and proactive, invasive diagnostic approach with needed testing to identify the potential pathogen, is imperative in these patients. Early bronchoscopy with bronchoalveolar lavage remains the most sensitive test to identify pathogens. Therapy can then be tailored toward the identified pathogen.

As part of the Chest Infections NetWork, we would like to raise awareness of lung infections in unique subgroups, such as lung transplant recipients. Treating infections in such patients requires a high index of suspicion in the setting of an atypical presentation.

Raed Alalawi, MD, FCCP
Steering Committee Member
 

Interprofessional Team

Extracorporeal Membrane Oxygenation (ECMO) in Near Fatal Asthma

Use of early ECMO to permit spontaneous breathing while the circuit accomplishes required ventilation and oxygenation seems more ideal. Avoidance of mechanical ventilation not only prevents complications like barotrauma but also may reduce delirium, malnutrition, and neuromuscular dysfunction. Performing “awake” ECMO has successfully been described for obstructive airway disease (Langer T, et al. Critical Care. 2016;20[1]:150). Factors limiting this approach are the invasive nature of ECMO and the inherent risks of large cannula dislodgement; however, the safety of this has been demonstrated with ambulation of ECMO patients to receive physical therapy (Abrams D, et al. Ann Cardiothorac Surg. 2019;8[1]:44). Alternatively, extracorporeal carbon dioxide removal (ECCO2R) systems utilize smaller catheters to satisfactorily remove CO₂ while oxygen supplementation could be achieved via nasal cannula (Pisani L, et al. Respiratory Care. 2018;63[9]:1174). Incorporation of ECMO in select cases of NFA, especially ECCO2R, should be considered as an early rather than rescue therapy for acute severe asthma refractory to conventional medical therapy.

Robert Baeten, DMSc, PA-C, FCCP
Steering Committee Member

Munish Luthra MD, FCCP
Steering Committee Member
 

Clinical Pulmonary Medicine

Pulmonary embolism in pregnancy: A diagnostic conundrum

Pulmonary embolism (PE) is the 6th leading cause of maternal mortality in the United States. The clinical signs and symptoms of PE are usually nonspecific and often overlap with the normal physiologic changes of pregnancy. Due to low specificity and sensitivity of D-dimer test, pregnant patients with suspected PE often undergo CT pulmonary angiography (CTPA) and ventilation-perfusion scanning, both of which can cause radiation exposure to mother and fetus.

To answer whether pregnancy-adapted YEARS algorithm (Van der Hulle T et al. Lancet. 2017;390[10091]:289) can be safely used to avoid diagnostic imaging, Artemis Study Investigators prospectively studied three criteria from YEARS algorithm in combination with a D-dimer level (Van der Pol et al. N Engl J Med. 2019;380[12]:1139. The three criteria included clinical signs of deep-vein thrombosis (DVT), hemoptysis, and PE as the most likely diagnosis. PE was considered ruled out when none of the three criteria were present and D-dimer was less than 1000 ng/mL or if one or more of the criteria were met and D-dimer was less than 500 ng/mL. Patients in whom D-dimer was greater than 1000 ng/mL or in those with D-dimer greater than 500 ng/mL and had 1 or more of the YEARS algorithm criteria present, PE could not be ruled out and underwent CTPA. A modification of the criteria was done only for patients who had clinical signs of DVT at baseline. These patients underwent compression ultrasonography and if a clot was found, CTPA was not performed and patients were started on anticoagulation therapy. Those with negative DVT studies were subclassified based on D-dimer levels as the study population above. Patients in whom pulmonary embolism was not ruled out underwent CTPA. Of these 299 patients, 16 (5.4%) were confirmed to have PE at baseline.

In the remaining 195 patients in whom PE was ruled out on the basis of study protocol, a 3-month follow-up diagnosed one patient (0.51%) with VTE. Using pregnancy-adapted YEARS algorithm, CTPA was avoided in 39% of the patients of which 65% were in their first trimester when the radiation exposure can be most harmful to the fetus.

Muhammad Adrish, MD, FCCP
Steering Committee Member

Munish Luthra, MD, FCCP
Steering Committee Member
 

Cardiovascular Medicine and Surgery

Physical examination of low cardiac output in the ICU

Regarding determination of shock etiology, in a small series of patients with systolic blood pressure < 90 mm Hg, physical exam findings of relatively warm skin temperature and rapid capillary refill had 89% sensitivity for vasodilatory shock, and jugular venous pressure ≥8 had 82% sensitivity for cardiogenic etiologies (Vazquez, et al. J Hosp Med. 2010;5[8]:471). Thus, while physical exam findings may inform bedside shock assessment, their accuracy is limited. Critical care physicians should consider additional assessment techniques, such as echocardiography or invasive hemodynamic monitoring, if diagnostic uncertainty persists (Vincent, et al. N Engl J Med. 2013;369[18]:1726).

Benjamin Kenigsberg, MD
Steering Committee Member

Dr. David Bowton and Dr. Steven Hollenberg contributed to the article.
 

Chest Infections

Lung infections in the transplant recipients

Multiple factors contribute to this increased infection risk, including donor lung colonization, disruption of local host defenses, constant contact with environmental pathogens, and heavy immunosuppression (Redmund KF, et al. Proc Am Thorac Soc. 2009;6[1]:94).

The onset of infectious manifestations, from the time of transplantation, is variable, depending on the organism. Based on the time of onset, infections can be categorized into within the first month posttransplant, 1 to 6 months, and beyond 6 months, posttransplant. During the first month, because of allograft colonization, preexisting infections in the recipient, and surgical- and hospital-acquired nosocomial infections are more common. The first 6 months are where the patients are at the highest risk for opportunistic infections. As the immunosuppression is lowered after 6 months, the causative organisms tend to be more common pathogens (Green M. Am J Transplant. 2013;13 [suppl 4]:3-8).

An early, aggressive, empiric antimicrobial therapy initiation and proactive, invasive diagnostic approach with needed testing to identify the potential pathogen, is imperative in these patients. Early bronchoscopy with bronchoalveolar lavage remains the most sensitive test to identify pathogens. Therapy can then be tailored toward the identified pathogen.

As part of the Chest Infections NetWork, we would like to raise awareness of lung infections in unique subgroups, such as lung transplant recipients. Treating infections in such patients requires a high index of suspicion in the setting of an atypical presentation.

Raed Alalawi, MD, FCCP
Steering Committee Member
 

Interprofessional Team

Extracorporeal Membrane Oxygenation (ECMO) in Near Fatal Asthma

Use of early ECMO to permit spontaneous breathing while the circuit accomplishes required ventilation and oxygenation seems more ideal. Avoidance of mechanical ventilation not only prevents complications like barotrauma but also may reduce delirium, malnutrition, and neuromuscular dysfunction. Performing “awake” ECMO has successfully been described for obstructive airway disease (Langer T, et al. Critical Care. 2016;20[1]:150). Factors limiting this approach are the invasive nature of ECMO and the inherent risks of large cannula dislodgement; however, the safety of this has been demonstrated with ambulation of ECMO patients to receive physical therapy (Abrams D, et al. Ann Cardiothorac Surg. 2019;8[1]:44). Alternatively, extracorporeal carbon dioxide removal (ECCO2R) systems utilize smaller catheters to satisfactorily remove CO₂ while oxygen supplementation could be achieved via nasal cannula (Pisani L, et al. Respiratory Care. 2018;63[9]:1174). Incorporation of ECMO in select cases of NFA, especially ECCO2R, should be considered as an early rather than rescue therapy for acute severe asthma refractory to conventional medical therapy.

Robert Baeten, DMSc, PA-C, FCCP
Steering Committee Member

Munish Luthra MD, FCCP
Steering Committee Member
 

Clinical Pulmonary Medicine

Pulmonary embolism in pregnancy: A diagnostic conundrum

Pulmonary embolism (PE) is the 6th leading cause of maternal mortality in the United States. The clinical signs and symptoms of PE are usually nonspecific and often overlap with the normal physiologic changes of pregnancy. Due to low specificity and sensitivity of D-dimer test, pregnant patients with suspected PE often undergo CT pulmonary angiography (CTPA) and ventilation-perfusion scanning, both of which can cause radiation exposure to mother and fetus.

To answer whether pregnancy-adapted YEARS algorithm (Van der Hulle T et al. Lancet. 2017;390[10091]:289) can be safely used to avoid diagnostic imaging, Artemis Study Investigators prospectively studied three criteria from YEARS algorithm in combination with a D-dimer level (Van der Pol et al. N Engl J Med. 2019;380[12]:1139. The three criteria included clinical signs of deep-vein thrombosis (DVT), hemoptysis, and PE as the most likely diagnosis. PE was considered ruled out when none of the three criteria were present and D-dimer was less than 1000 ng/mL or if one or more of the criteria were met and D-dimer was less than 500 ng/mL. Patients in whom D-dimer was greater than 1000 ng/mL or in those with D-dimer greater than 500 ng/mL and had 1 or more of the YEARS algorithm criteria present, PE could not be ruled out and underwent CTPA. A modification of the criteria was done only for patients who had clinical signs of DVT at baseline. These patients underwent compression ultrasonography and if a clot was found, CTPA was not performed and patients were started on anticoagulation therapy. Those with negative DVT studies were subclassified based on D-dimer levels as the study population above. Patients in whom pulmonary embolism was not ruled out underwent CTPA. Of these 299 patients, 16 (5.4%) were confirmed to have PE at baseline.

In the remaining 195 patients in whom PE was ruled out on the basis of study protocol, a 3-month follow-up diagnosed one patient (0.51%) with VTE. Using pregnancy-adapted YEARS algorithm, CTPA was avoided in 39% of the patients of which 65% were in their first trimester when the radiation exposure can be most harmful to the fetus.

Muhammad Adrish, MD, FCCP
Steering Committee Member

Munish Luthra, MD, FCCP
Steering Committee Member
 

Cardiovascular Medicine and Surgery

Physical examination of low cardiac output in the ICU

Regarding determination of shock etiology, in a small series of patients with systolic blood pressure < 90 mm Hg, physical exam findings of relatively warm skin temperature and rapid capillary refill had 89% sensitivity for vasodilatory shock, and jugular venous pressure ≥8 had 82% sensitivity for cardiogenic etiologies (Vazquez, et al. J Hosp Med. 2010;5[8]:471). Thus, while physical exam findings may inform bedside shock assessment, their accuracy is limited. Critical care physicians should consider additional assessment techniques, such as echocardiography or invasive hemodynamic monitoring, if diagnostic uncertainty persists (Vincent, et al. N Engl J Med. 2013;369[18]:1726).

Benjamin Kenigsberg, MD
Steering Committee Member

Dr. David Bowton and Dr. Steven Hollenberg contributed to the article.
 

Chest Infections

Lung infections in the transplant recipients

Multiple factors contribute to this increased infection risk, including donor lung colonization, disruption of local host defenses, constant contact with environmental pathogens, and heavy immunosuppression (Redmund KF, et al. Proc Am Thorac Soc. 2009;6[1]:94).

The onset of infectious manifestations, from the time of transplantation, is variable, depending on the organism. Based on the time of onset, infections can be categorized into within the first month posttransplant, 1 to 6 months, and beyond 6 months, posttransplant. During the first month, because of allograft colonization, preexisting infections in the recipient, and surgical- and hospital-acquired nosocomial infections are more common. The first 6 months are where the patients are at the highest risk for opportunistic infections. As the immunosuppression is lowered after 6 months, the causative organisms tend to be more common pathogens (Green M. Am J Transplant. 2013;13 [suppl 4]:3-8).

An early, aggressive, empiric antimicrobial therapy initiation and proactive, invasive diagnostic approach with needed testing to identify the potential pathogen, is imperative in these patients. Early bronchoscopy with bronchoalveolar lavage remains the most sensitive test to identify pathogens. Therapy can then be tailored toward the identified pathogen.

As part of the Chest Infections NetWork, we would like to raise awareness of lung infections in unique subgroups, such as lung transplant recipients. Treating infections in such patients requires a high index of suspicion in the setting of an atypical presentation.

Raed Alalawi, MD, FCCP
Steering Committee Member
 

Interprofessional Team

Extracorporeal Membrane Oxygenation (ECMO) in Near Fatal Asthma

Use of early ECMO to permit spontaneous breathing while the circuit accomplishes required ventilation and oxygenation seems more ideal. Avoidance of mechanical ventilation not only prevents complications like barotrauma but also may reduce delirium, malnutrition, and neuromuscular dysfunction. Performing “awake” ECMO has successfully been described for obstructive airway disease (Langer T, et al. Critical Care. 2016;20[1]:150). Factors limiting this approach are the invasive nature of ECMO and the inherent risks of large cannula dislodgement; however, the safety of this has been demonstrated with ambulation of ECMO patients to receive physical therapy (Abrams D, et al. Ann Cardiothorac Surg. 2019;8[1]:44). Alternatively, extracorporeal carbon dioxide removal (ECCO2R) systems utilize smaller catheters to satisfactorily remove CO₂ while oxygen supplementation could be achieved via nasal cannula (Pisani L, et al. Respiratory Care. 2018;63[9]:1174). Incorporation of ECMO in select cases of NFA, especially ECCO2R, should be considered as an early rather than rescue therapy for acute severe asthma refractory to conventional medical therapy.

Robert Baeten, DMSc, PA-C, FCCP
Steering Committee Member

Munish Luthra MD, FCCP
Steering Committee Member
 

What makes the traditional New Orleans food so special? The flair and broad history for these dishes unite the city and the love for all things tasty with its seafood, Creole, Cajun, and many other types of food options. We’ve picked five famous New Orleans dishes that you should try while you attend CHEST 2019.

GUMBO

As one of Louisiana’s quintessential dishes, you can find gumbo in restaurants, at events, and homes all over the state. Claiming both French and West African roots, there’s no one way to make gumbo, but it is usually served over rice and with a wide variety of other ingredients. With so many different recipes that each family and cook has perfected to be the “best,” most cooks tend to guard their recipes closely.

CRAWFISH ETOUFFEE

The word étouffée (pronounced eh-too-fey) comes from the French word “to smother.” This dish is a very thick stew full of crawfish (or shrimp) served over rice. It is also similar in some way to gumbo – same types of Creole seasonings, served over rice, and made with a roux – but it is often made with a “blonde” roux, which is lighter in color and gives an almost sweet flavor. It’s a taste that’s worth trying and claimed you won’t forget.

JAMBALAYA

Another famous and traditional New Orleans dish is jambalaya. This is a rice dish that is a culinary staple of the city with a history from the time when colonial Spanish settlers tried reconstructing their native paella from locally sourced ingredients. It typically contains a mix of meat, vegetables, spices, and rice, combined in a variety of ways.

PO-BOYS

This classic French bread sandwich is stuffed and slathered with sauce. Filled with lettuce, tomato, and pickles, it’s usually whatever filled with whatever meat you choose – roast beef, fried shrimp, oysters. This allows for many types of po-boy sandwiches. You tend to see very creative po-boys at the Oak Street Po-Boy Festival each year.

BEIGNETS

These pastries are more than just a doughnut and are famous for being a doughnut without the hole. As the city’s most popular sweet treat and staple, locals and visitors can enjoy beignets all year long, available 24-hours a day in New Orleans at more than one coffee hotspot.

What makes the traditional New Orleans food so special? The flair and broad history for these dishes unite the city and the love for all things tasty with its seafood, Creole, Cajun, and many other types of food options. We’ve picked five famous New Orleans dishes that you should try while you attend CHEST 2019.

GUMBO

As one of Louisiana’s quintessential dishes, you can find gumbo in restaurants, at events, and homes all over the state. Claiming both French and West African roots, there’s no one way to make gumbo, but it is usually served over rice and with a wide variety of other ingredients. With so many different recipes that each family and cook has perfected to be the “best,” most cooks tend to guard their recipes closely.

CRAWFISH ETOUFFEE

The word étouffée (pronounced eh-too-fey) comes from the French word “to smother.” This dish is a very thick stew full of crawfish (or shrimp) served over rice. It is also similar in some way to gumbo – same types of Creole seasonings, served over rice, and made with a roux – but it is often made with a “blonde” roux, which is lighter in color and gives an almost sweet flavor. It’s a taste that’s worth trying and claimed you won’t forget.

JAMBALAYA

Another famous and traditional New Orleans dish is jambalaya. This is a rice dish that is a culinary staple of the city with a history from the time when colonial Spanish settlers tried reconstructing their native paella from locally sourced ingredients. It typically contains a mix of meat, vegetables, spices, and rice, combined in a variety of ways.

PO-BOYS

This classic French bread sandwich is stuffed and slathered with sauce. Filled with lettuce, tomato, and pickles, it’s usually whatever filled with whatever meat you choose – roast beef, fried shrimp, oysters. This allows for many types of po-boy sandwiches. You tend to see very creative po-boys at the Oak Street Po-Boy Festival each year.

BEIGNETS

These pastries are more than just a doughnut and are famous for being a doughnut without the hole. As the city’s most popular sweet treat and staple, locals and visitors can enjoy beignets all year long, available 24-hours a day in New Orleans at more than one coffee hotspot.

What makes the traditional New Orleans food so special? The flair and broad history for these dishes unite the city and the love for all things tasty with its seafood, Creole, Cajun, and many other types of food options. We’ve picked five famous New Orleans dishes that you should try while you attend CHEST 2019.

GUMBO

As one of Louisiana’s quintessential dishes, you can find gumbo in restaurants, at events, and homes all over the state. Claiming both French and West African roots, there’s no one way to make gumbo, but it is usually served over rice and with a wide variety of other ingredients. With so many different recipes that each family and cook has perfected to be the “best,” most cooks tend to guard their recipes closely.

CRAWFISH ETOUFFEE

The word étouffée (pronounced eh-too-fey) comes from the French word “to smother.” This dish is a very thick stew full of crawfish (or shrimp) served over rice. It is also similar in some way to gumbo – same types of Creole seasonings, served over rice, and made with a roux – but it is often made with a “blonde” roux, which is lighter in color and gives an almost sweet flavor. It’s a taste that’s worth trying and claimed you won’t forget.

JAMBALAYA

Another famous and traditional New Orleans dish is jambalaya. This is a rice dish that is a culinary staple of the city with a history from the time when colonial Spanish settlers tried reconstructing their native paella from locally sourced ingredients. It typically contains a mix of meat, vegetables, spices, and rice, combined in a variety of ways.

PO-BOYS

This classic French bread sandwich is stuffed and slathered with sauce. Filled with lettuce, tomato, and pickles, it’s usually whatever filled with whatever meat you choose – roast beef, fried shrimp, oysters. This allows for many types of po-boy sandwiches. You tend to see very creative po-boys at the Oak Street Po-Boy Festival each year.

BEIGNETS

These pastries are more than just a doughnut and are famous for being a doughnut without the hole. As the city’s most popular sweet treat and staple, locals and visitors can enjoy beignets all year long, available 24-hours a day in New Orleans at more than one coffee hotspot.

Does this sound like your day?

You show up to work after a terrible night’s sleep. Your back is tense, and you do some kind of walking/stretching combo as you walk through the doors. Your focus fades during the mind-numbing routine of the morning shift sign out. As the day moves forward, you begin to feel resentful as you sign orders, see patients, and address your ICU team needs. You know that’s not right, that it’s not in line with who you want to be, but the irritation doesn’t go away.

Your lunchtime is filled with computer screens, notes, billing, and more billing. The previous feelings of irritation begin to boil into anger because more of your day is filled with bureaucratic demands and insurance reports rather than actually helping people. This isn’t what you signed up for. Years and years of training so you could be a paper pusher? The thought leads to rage ... or sometimes apathy on days you give in to the inevitable.

You finish your shift with admissions, procedures, code blues, and an overwhelming and exhausting night shift sign out. You feel like a hamster in a wheel. You’re going nowhere. What’s the point of all of this? You find yourself questioning why you went into medicine anyways ... yeah, that’s burnout.

I know what you’re thinking. You keep hearing about this, and it’s important to recognize, but then you hear the same old solutions: be more positive, find balance, do some yoga, take this resilience module, be mindful (what on earth does this mean anyways?), get some more sleep. Basically, it’s our problem. It’s our burden. If all of these were easy to understand and implement, don’t you think doctors and health-care providers would have done it already? I think you and I are a lot alike. These were my exact feelings. But stick with me on this one. I have a solution for you, albeit a little different. I’ll show you a more “positive” spin on the DIY.

I burned out early. After fellowship, I didn’t want to be a doctor anymore. I desperately sought to alter my career somehow. I looked into website development, something I had been good at in high school. I took a few refresher classes on my days off and started coding my own sites, but I had bills to pay. Big bills. Student loan bills. Luckily, my first job out of fellowship accepted many of my schedule demands, such as day shifts only, and after about a year, I recovered and remembered why I had loved medicine to begin with.
 

What is burnout?

Mind-body-soul exhaustion caused by excessive stress. Stress and burnout are closely related, but they’re more like distant cousins. Stress can be (and is) a normal part of our jobs. I bet you think you’re stressed, when you’re probably burned out. Critical care doctors have the highest rate of burnout among all physician subspecialties at >55%, and it is even higher in pediatric critical care. (Sessler C. https://www.mdedge.com/chestphysician/article/160951/society-news/turning-heat-icu-burnout). The main difference between stress and burnout is hope. With stress, you still feel like things can get better and you can get it all under control. Burnout feels hopeless.

What are the three core symptoms of burnout?

• Irritability and impatience with patients (depersonalization)

• Cynicism and difficulty concentrating (emotional exhaustion)

• What’s the point of all of this? Nothing I do matters or is appreciated (decreased self-efficacy)


We can talk about the symptoms of burnout all day, but what does that really look like? It looks like the day we described at the beginning. You know, the day that resonated with you and caused you to keep reading.
 

Why should we all be discussing this important topic?

Being burned out not only affects us on a soul level (achingly described above), but, more importantly, this can trickle down to our personal lives, family relationships, and how we care for our patients, with some studies showing that it affects our performance and, gulp, patient outcomes. That’s scary (Moss M et al. Crit Care Med. 2016;44[7]:1414).

Causes of burnout

There are many causes of burnout, and several studies have identified risk factors. A lack of control, conflicts with colleagues and leadership, and performing menial tasks can add to the irritation of a workday. This doesn’t even include the nature of our actual job as critical care doctors. We care for the sickest and are frequently involved in end-of-life care. Over time, the stress morphs into burnout. Female gender is also an independent risk factor for doctors (Pastores SM, et al. Crit Care Med. 2019;47[4]:550).

We’ve identified it. We’ve quantified it. But we’re not fixing it. In fact, there are only a few studies that have incorporated a needs assessment of doctors, paired with appropriate environmental intervention. A study done with primary care doctors in New York City clinics found that surveying a doctor’s “wish list” of interventions can help identify gaps in workflow, such as pairing one medical assistant with each attending (Linzer M, et al. J Gen Intern Med. 2015;30[8]:1105).

Without more data like this, we’re hamsters in a wheel. Luckily, organizations like CHEST have joined together with others to create the Critical Care Societies Collaborative and have an annual summit to discuss research strategies.
 

Solutions

Even millennials are sick of the mindful “chore” list. Yoga pants, yoga mats, crystals, chakras, meditation, and the list goes on and on. What millennials want are work-life integrations that are easy; workspaces that invite mindful behavior and daily rituals that excite and relax them. Co-working spaces like WeWork have designated self-care spaces.

Self-care is now essential, not an indulgence. I wasn’t sure how to create this space in my ICU, so I started small, with things I could carry with myself. The key is to find small rituals with big meanings. What could this look like for you? I began doing breathwork. Frankly, the idea came to me from my Apple® watch. It just started giving me these reminders one day, and I decided to take it seriously. I found that my mind and muscles eased after only 1 minute of breathing in and out slowly. This elevated my mood and was the refresher I needed in the afternoons. My body ached less after procedures.

I also got a little woo-woo (stay with me now) and began carrying around crystal stones. You don’t have to carry around crystals. Prayer books, religious symbols, your child’s toy car, anything can work if it has meaning for you, so when you see it or touch it during your day, you remember your big why. Why you’re serving people. Why you’re a doctor. I prefer the crystals over jewelry because it’s something unusual that I don’t expect to be sitting in my pocket. It’s always a nice gentle reminder of the love I have for my patients, my job, and humanity. When I put my hands in my pocket as I’m talking to yet another frustrated family member, my responses are more patient and calmer, which leads to a more productive conversation.

Lastly, I started what I call a new Pavlov home routine. When I’m done with work, I light a candle and write out three things I’m grateful for. Retrain your brain. Retrain your triggers. What’s your Pavlov’s bell going to be? Many of us come home hungry and stressed. Food then becomes linked to stress. This is not good. Link it with something else. Light a candle, count to 3, then blow it out. Use your kids to incorporate something fun. Use a toy with “super powers” to “beam” the bad feelings away. Taking a few extra minutes to shift gears has created a much happier home for me.

There are things that we can’t control. That’s called circumstances. We can’t control other people; we can’t control the hospital system; we can’t control our past. But the rest of everything we can control: our thoughts, feelings, and daily self-care rituals.

It reminds me of something my dad always said when I was a little girl. When crossing the street, you always look twice, oftentimes three. Why be so careful? It’s the pedestrian’s right of way after all. “Well..” he replied, “If a car hits you, nothing much happens to them, but your entire life will be destroyed, forever.”

Stop walking into traffic thinking everything will be ok. Take control of what you can.

Look, I get it. As health-care providers, we are an independent group. But just because you can do it alone, doesn’t mean you have to.

Choose one thing. Whether it be something I mentioned or something that came to your mind as you read this. Then, drop me a line at my personal email roozehra.khan.do@gmail.com. I will send you a reply to let you know I hear you and I’m in your corner.

Burnout happens.

But, so does joy, job satisfaction, and balance. Those things just take more effort.

Dr. Khan is Assistant Editor, Web and Multimedia, CHEST^® journal.

Does this sound like your day?

You show up to work after a terrible night’s sleep. Your back is tense, and you do some kind of walking/stretching combo as you walk through the doors. Your focus fades during the mind-numbing routine of the morning shift sign out. As the day moves forward, you begin to feel resentful as you sign orders, see patients, and address your ICU team needs. You know that’s not right, that it’s not in line with who you want to be, but the irritation doesn’t go away.

Your lunchtime is filled with computer screens, notes, billing, and more billing. The previous feelings of irritation begin to boil into anger because more of your day is filled with bureaucratic demands and insurance reports rather than actually helping people. This isn’t what you signed up for. Years and years of training so you could be a paper pusher? The thought leads to rage ... or sometimes apathy on days you give in to the inevitable.

You finish your shift with admissions, procedures, code blues, and an overwhelming and exhausting night shift sign out. You feel like a hamster in a wheel. You’re going nowhere. What’s the point of all of this? You find yourself questioning why you went into medicine anyways ... yeah, that’s burnout.

I know what you’re thinking. You keep hearing about this, and it’s important to recognize, but then you hear the same old solutions: be more positive, find balance, do some yoga, take this resilience module, be mindful (what on earth does this mean anyways?), get some more sleep. Basically, it’s our problem. It’s our burden. If all of these were easy to understand and implement, don’t you think doctors and health-care providers would have done it already? I think you and I are a lot alike. These were my exact feelings. But stick with me on this one. I have a solution for you, albeit a little different. I’ll show you a more “positive” spin on the DIY.

I burned out early. After fellowship, I didn’t want to be a doctor anymore. I desperately sought to alter my career somehow. I looked into website development, something I had been good at in high school. I took a few refresher classes on my days off and started coding my own sites, but I had bills to pay. Big bills. Student loan bills. Luckily, my first job out of fellowship accepted many of my schedule demands, such as day shifts only, and after about a year, I recovered and remembered why I had loved medicine to begin with.
 

What is burnout?

Mind-body-soul exhaustion caused by excessive stress. Stress and burnout are closely related, but they’re more like distant cousins. Stress can be (and is) a normal part of our jobs. I bet you think you’re stressed, when you’re probably burned out. Critical care doctors have the highest rate of burnout among all physician subspecialties at >55%, and it is even higher in pediatric critical care. (Sessler C. https://www.mdedge.com/chestphysician/article/160951/society-news/turning-heat-icu-burnout). The main difference between stress and burnout is hope. With stress, you still feel like things can get better and you can get it all under control. Burnout feels hopeless.

What are the three core symptoms of burnout?

• Irritability and impatience with patients (depersonalization)

• Cynicism and difficulty concentrating (emotional exhaustion)

• What’s the point of all of this? Nothing I do matters or is appreciated (decreased self-efficacy)


We can talk about the symptoms of burnout all day, but what does that really look like? It looks like the day we described at the beginning. You know, the day that resonated with you and caused you to keep reading.
 

Why should we all be discussing this important topic?

Being burned out not only affects us on a soul level (achingly described above), but, more importantly, this can trickle down to our personal lives, family relationships, and how we care for our patients, with some studies showing that it affects our performance and, gulp, patient outcomes. That’s scary (Moss M et al. Crit Care Med. 2016;44[7]:1414).

Causes of burnout

There are many causes of burnout, and several studies have identified risk factors. A lack of control, conflicts with colleagues and leadership, and performing menial tasks can add to the irritation of a workday. This doesn’t even include the nature of our actual job as critical care doctors. We care for the sickest and are frequently involved in end-of-life care. Over time, the stress morphs into burnout. Female gender is also an independent risk factor for doctors (Pastores SM, et al. Crit Care Med. 2019;47[4]:550).

We’ve identified it. We’ve quantified it. But we’re not fixing it. In fact, there are only a few studies that have incorporated a needs assessment of doctors, paired with appropriate environmental intervention. A study done with primary care doctors in New York City clinics found that surveying a doctor’s “wish list” of interventions can help identify gaps in workflow, such as pairing one medical assistant with each attending (Linzer M, et al. J Gen Intern Med. 2015;30[8]:1105).

Without more data like this, we’re hamsters in a wheel. Luckily, organizations like CHEST have joined together with others to create the Critical Care Societies Collaborative and have an annual summit to discuss research strategies.
 

Solutions

Even millennials are sick of the mindful “chore” list. Yoga pants, yoga mats, crystals, chakras, meditation, and the list goes on and on. What millennials want are work-life integrations that are easy; workspaces that invite mindful behavior and daily rituals that excite and relax them. Co-working spaces like WeWork have designated self-care spaces.

Self-care is now essential, not an indulgence. I wasn’t sure how to create this space in my ICU, so I started small, with things I could carry with myself. The key is to find small rituals with big meanings. What could this look like for you? I began doing breathwork. Frankly, the idea came to me from my Apple® watch. It just started giving me these reminders one day, and I decided to take it seriously. I found that my mind and muscles eased after only 1 minute of breathing in and out slowly. This elevated my mood and was the refresher I needed in the afternoons. My body ached less after procedures.

I also got a little woo-woo (stay with me now) and began carrying around crystal stones. You don’t have to carry around crystals. Prayer books, religious symbols, your child’s toy car, anything can work if it has meaning for you, so when you see it or touch it during your day, you remember your big why. Why you’re serving people. Why you’re a doctor. I prefer the crystals over jewelry because it’s something unusual that I don’t expect to be sitting in my pocket. It’s always a nice gentle reminder of the love I have for my patients, my job, and humanity. When I put my hands in my pocket as I’m talking to yet another frustrated family member, my responses are more patient and calmer, which leads to a more productive conversation.

Lastly, I started what I call a new Pavlov home routine. When I’m done with work, I light a candle and write out three things I’m grateful for. Retrain your brain. Retrain your triggers. What’s your Pavlov’s bell going to be? Many of us come home hungry and stressed. Food then becomes linked to stress. This is not good. Link it with something else. Light a candle, count to 3, then blow it out. Use your kids to incorporate something fun. Use a toy with “super powers” to “beam” the bad feelings away. Taking a few extra minutes to shift gears has created a much happier home for me.

There are things that we can’t control. That’s called circumstances. We can’t control other people; we can’t control the hospital system; we can’t control our past. But the rest of everything we can control: our thoughts, feelings, and daily self-care rituals.

It reminds me of something my dad always said when I was a little girl. When crossing the street, you always look twice, oftentimes three. Why be so careful? It’s the pedestrian’s right of way after all. “Well..” he replied, “If a car hits you, nothing much happens to them, but your entire life will be destroyed, forever.”

Stop walking into traffic thinking everything will be ok. Take control of what you can.

Look, I get it. As health-care providers, we are an independent group. But just because you can do it alone, doesn’t mean you have to.

Choose one thing. Whether it be something I mentioned or something that came to your mind as you read this. Then, drop me a line at my personal email roozehra.khan.do@gmail.com. I will send you a reply to let you know I hear you and I’m in your corner.

Burnout happens.

But, so does joy, job satisfaction, and balance. Those things just take more effort.

Dr. Khan is Assistant Editor, Web and Multimedia, CHEST^® journal.

Does this sound like your day?

You show up to work after a terrible night’s sleep. Your back is tense, and you do some kind of walking/stretching combo as you walk through the doors. Your focus fades during the mind-numbing routine of the morning shift sign out. As the day moves forward, you begin to feel resentful as you sign orders, see patients, and address your ICU team needs. You know that’s not right, that it’s not in line with who you want to be, but the irritation doesn’t go away.

Your lunchtime is filled with computer screens, notes, billing, and more billing. The previous feelings of irritation begin to boil into anger because more of your day is filled with bureaucratic demands and insurance reports rather than actually helping people. This isn’t what you signed up for. Years and years of training so you could be a paper pusher? The thought leads to rage ... or sometimes apathy on days you give in to the inevitable.

You finish your shift with admissions, procedures, code blues, and an overwhelming and exhausting night shift sign out. You feel like a hamster in a wheel. You’re going nowhere. What’s the point of all of this? You find yourself questioning why you went into medicine anyways ... yeah, that’s burnout.

I know what you’re thinking. You keep hearing about this, and it’s important to recognize, but then you hear the same old solutions: be more positive, find balance, do some yoga, take this resilience module, be mindful (what on earth does this mean anyways?), get some more sleep. Basically, it’s our problem. It’s our burden. If all of these were easy to understand and implement, don’t you think doctors and health-care providers would have done it already? I think you and I are a lot alike. These were my exact feelings. But stick with me on this one. I have a solution for you, albeit a little different. I’ll show you a more “positive” spin on the DIY.

I burned out early. After fellowship, I didn’t want to be a doctor anymore. I desperately sought to alter my career somehow. I looked into website development, something I had been good at in high school. I took a few refresher classes on my days off and started coding my own sites, but I had bills to pay. Big bills. Student loan bills. Luckily, my first job out of fellowship accepted many of my schedule demands, such as day shifts only, and after about a year, I recovered and remembered why I had loved medicine to begin with.
 

What is burnout?

Mind-body-soul exhaustion caused by excessive stress. Stress and burnout are closely related, but they’re more like distant cousins. Stress can be (and is) a normal part of our jobs. I bet you think you’re stressed, when you’re probably burned out. Critical care doctors have the highest rate of burnout among all physician subspecialties at >55%, and it is even higher in pediatric critical care. (Sessler C. https://www.mdedge.com/chestphysician/article/160951/society-news/turning-heat-icu-burnout). The main difference between stress and burnout is hope. With stress, you still feel like things can get better and you can get it all under control. Burnout feels hopeless.

What are the three core symptoms of burnout?

• Irritability and impatience with patients (depersonalization)

• Cynicism and difficulty concentrating (emotional exhaustion)

• What’s the point of all of this? Nothing I do matters or is appreciated (decreased self-efficacy)


We can talk about the symptoms of burnout all day, but what does that really look like? It looks like the day we described at the beginning. You know, the day that resonated with you and caused you to keep reading.
 

Why should we all be discussing this important topic?

Being burned out not only affects us on a soul level (achingly described above), but, more importantly, this can trickle down to our personal lives, family relationships, and how we care for our patients, with some studies showing that it affects our performance and, gulp, patient outcomes. That’s scary (Moss M et al. Crit Care Med. 2016;44[7]:1414).

Causes of burnout

There are many causes of burnout, and several studies have identified risk factors. A lack of control, conflicts with colleagues and leadership, and performing menial tasks can add to the irritation of a workday. This doesn’t even include the nature of our actual job as critical care doctors. We care for the sickest and are frequently involved in end-of-life care. Over time, the stress morphs into burnout. Female gender is also an independent risk factor for doctors (Pastores SM, et al. Crit Care Med. 2019;47[4]:550).

We’ve identified it. We’ve quantified it. But we’re not fixing it. In fact, there are only a few studies that have incorporated a needs assessment of doctors, paired with appropriate environmental intervention. A study done with primary care doctors in New York City clinics found that surveying a doctor’s “wish list” of interventions can help identify gaps in workflow, such as pairing one medical assistant with each attending (Linzer M, et al. J Gen Intern Med. 2015;30[8]:1105).

Without more data like this, we’re hamsters in a wheel. Luckily, organizations like CHEST have joined together with others to create the Critical Care Societies Collaborative and have an annual summit to discuss research strategies.
 

Solutions

Even millennials are sick of the mindful “chore” list. Yoga pants, yoga mats, crystals, chakras, meditation, and the list goes on and on. What millennials want are work-life integrations that are easy; workspaces that invite mindful behavior and daily rituals that excite and relax them. Co-working spaces like WeWork have designated self-care spaces.

Self-care is now essential, not an indulgence. I wasn’t sure how to create this space in my ICU, so I started small, with things I could carry with myself. The key is to find small rituals with big meanings. What could this look like for you? I began doing breathwork. Frankly, the idea came to me from my Apple® watch. It just started giving me these reminders one day, and I decided to take it seriously. I found that my mind and muscles eased after only 1 minute of breathing in and out slowly. This elevated my mood and was the refresher I needed in the afternoons. My body ached less after procedures.

I also got a little woo-woo (stay with me now) and began carrying around crystal stones. You don’t have to carry around crystals. Prayer books, religious symbols, your child’s toy car, anything can work if it has meaning for you, so when you see it or touch it during your day, you remember your big why. Why you’re serving people. Why you’re a doctor. I prefer the crystals over jewelry because it’s something unusual that I don’t expect to be sitting in my pocket. It’s always a nice gentle reminder of the love I have for my patients, my job, and humanity. When I put my hands in my pocket as I’m talking to yet another frustrated family member, my responses are more patient and calmer, which leads to a more productive conversation.

Lastly, I started what I call a new Pavlov home routine. When I’m done with work, I light a candle and write out three things I’m grateful for. Retrain your brain. Retrain your triggers. What’s your Pavlov’s bell going to be? Many of us come home hungry and stressed. Food then becomes linked to stress. This is not good. Link it with something else. Light a candle, count to 3, then blow it out. Use your kids to incorporate something fun. Use a toy with “super powers” to “beam” the bad feelings away. Taking a few extra minutes to shift gears has created a much happier home for me.

There are things that we can’t control. That’s called circumstances. We can’t control other people; we can’t control the hospital system; we can’t control our past. But the rest of everything we can control: our thoughts, feelings, and daily self-care rituals.

It reminds me of something my dad always said when I was a little girl. When crossing the street, you always look twice, oftentimes three. Why be so careful? It’s the pedestrian’s right of way after all. “Well..” he replied, “If a car hits you, nothing much happens to them, but your entire life will be destroyed, forever.”

Stop walking into traffic thinking everything will be ok. Take control of what you can.

Look, I get it. As health-care providers, we are an independent group. But just because you can do it alone, doesn’t mean you have to.

Choose one thing. Whether it be something I mentioned or something that came to your mind as you read this. Then, drop me a line at my personal email roozehra.khan.do@gmail.com. I will send you a reply to let you know I hear you and I’m in your corner.

Burnout happens.

But, so does joy, job satisfaction, and balance. Those things just take more effort.

Dr. Khan is Assistant Editor, Web and Multimedia, CHEST^® journal.

As a leader in education for pulmonary, critical care, and sleep medicine, staying ahead of trends in its professional fields and across educational delivery, in general, is critical to remaining relevant and to best serve the membership. The leadership of the American College of Chest Physicians (CHEST) developed a multifaceted program this year entitled, “CHEST Inspiration,” a series of programmatic initiatives aimed at stimulating and encouraging innovation within the association and recognizing individuals with great ideas that streamline current processes or disrupt ways of traditional thinking about everyday problems.

The CHEST Board of Regents recently completed one of the first components of the CHEST Inspiration program – the 2019 CHEST Environmental Scan. This article describes the development of the 2019 CHEST Environmental Scan and its fit with the other components of CHEST Inspiration program.

Environmental scanning is a formal process for tracking trends and occurrences in an organization’s internal and external environment that bear on its success--currently and in the future. The environmental scanning process examines both quantitative and qualitative factors and identifies a set of key environmental indicators believed to have the most important impact on the organization’s work.

The 2019 CHEST Environmental Scan is a synthesis of work that took place in January 2019 at the CHEST Environmental Summit, a special joint session of the Board of Regents (BOR) and the CHEST Foundation Board of Trustees (BOT). In that session attendees attempted to free themselves from the usual concentrated focus on the College and Foundation missions, goals, and strategies, recognizing that a possible (even likely) unintended consequence of a narrow focus is losing sight of the outside world and the forces there that—like it or not—influence and could even disrupt the programs and strategies of CHEST and the CHEST Foundation.

To facilitate the process, CHEST engaged a market research and consulting agency with expertise in environmental scans and a client base of nonprofit organizations and associations. The consultant conducted secondary research organized around six drivers of change selected by CHEST leadership:

• Health Care

• Economy and Workforce

• Technology

• Education, Content Delivery, and Career Advancement

• Social, Political, Regulatory, and the Environment

• Philanthropy

The leadership had the opportunity to review the consultant’s research findings prior to the Environmental Summit. Then, in the in-person BOT/BOR summit meeting, the consultant’s research findings were discussed and debated and were addressed with the following questions:

• How will this trend impact members? How will it change their work environment and what they need to know?

• How will this trend impact CHEST? What are the challenges and opportunities?

• What responses or actions should CHEST take?

• Does this insight require changes to our strategic plan?

The consultant synthesized the debates and discussions and prepared a draft document that shaped this year’s document.

The 2019 CHEST Environmental Scan, which will be undated periodically, will be used to:

• Inform members about external developments and put each in perspective

• Help leadership and staff determine future directions and program opportunities

• Keep the 5-year strategic plan fresh and relevant

The environmental scan will be published in six monthly installments in CHEST Physician, with each installment addressing one of the drivers of change. Most of the content is confirming rather than revolutionary in nature. Each installment will be accompanied comments from one of four leading physician experts who will put the content into perspective.

The two other components of the CHEST Inspiration program are to engage a group of experts from outside the field of medicine and health care who are innovative and successful in their own professions. This focus group of professionals from outside of our association will be held in conjunction with the June Board of Regents meeting. An additional component to stimulate innovative thinking and celebrate great ideas will be a new competitive event at the annual meeting. Dubbed “CHEST FISH Bowl (Furthering Innovation and Science for Health),” this event will launch this month, with contestants submitting video applications that feature their great idea, and winners in selected categories to be selected at CHEST 2019 in New Orleans. CHEST Physician will be your source for information about all the CHEST Inspiration programs through a new series of articles called “CHEST Inspiration: Pacing the Future.”

As a leader in education for pulmonary, critical care, and sleep medicine, staying ahead of trends in its professional fields and across educational delivery, in general, is critical to remaining relevant and to best serve the membership. The leadership of the American College of Chest Physicians (CHEST) developed a multifaceted program this year entitled, “CHEST Inspiration,” a series of programmatic initiatives aimed at stimulating and encouraging innovation within the association and recognizing individuals with great ideas that streamline current processes or disrupt ways of traditional thinking about everyday problems.

The CHEST Board of Regents recently completed one of the first components of the CHEST Inspiration program – the 2019 CHEST Environmental Scan. This article describes the development of the 2019 CHEST Environmental Scan and its fit with the other components of CHEST Inspiration program.

Environmental scanning is a formal process for tracking trends and occurrences in an organization’s internal and external environment that bear on its success--currently and in the future. The environmental scanning process examines both quantitative and qualitative factors and identifies a set of key environmental indicators believed to have the most important impact on the organization’s work.

The 2019 CHEST Environmental Scan is a synthesis of work that took place in January 2019 at the CHEST Environmental Summit, a special joint session of the Board of Regents (BOR) and the CHEST Foundation Board of Trustees (BOT). In that session attendees attempted to free themselves from the usual concentrated focus on the College and Foundation missions, goals, and strategies, recognizing that a possible (even likely) unintended consequence of a narrow focus is losing sight of the outside world and the forces there that—like it or not—influence and could even disrupt the programs and strategies of CHEST and the CHEST Foundation.

To facilitate the process, CHEST engaged a market research and consulting agency with expertise in environmental scans and a client base of nonprofit organizations and associations. The consultant conducted secondary research organized around six drivers of change selected by CHEST leadership:

• Health Care

• Economy and Workforce

• Technology

• Education, Content Delivery, and Career Advancement

• Social, Political, Regulatory, and the Environment

• Philanthropy

The leadership had the opportunity to review the consultant’s research findings prior to the Environmental Summit. Then, in the in-person BOT/BOR summit meeting, the consultant’s research findings were discussed and debated and were addressed with the following questions:

• How will this trend impact members? How will it change their work environment and what they need to know?

• How will this trend impact CHEST? What are the challenges and opportunities?

• What responses or actions should CHEST take?

• Does this insight require changes to our strategic plan?

The consultant synthesized the debates and discussions and prepared a draft document that shaped this year’s document.

The 2019 CHEST Environmental Scan, which will be undated periodically, will be used to:

• Inform members about external developments and put each in perspective

• Help leadership and staff determine future directions and program opportunities

• Keep the 5-year strategic plan fresh and relevant

The environmental scan will be published in six monthly installments in CHEST Physician, with each installment addressing one of the drivers of change. Most of the content is confirming rather than revolutionary in nature. Each installment will be accompanied comments from one of four leading physician experts who will put the content into perspective.

The two other components of the CHEST Inspiration program are to engage a group of experts from outside the field of medicine and health care who are innovative and successful in their own professions. This focus group of professionals from outside of our association will be held in conjunction with the June Board of Regents meeting. An additional component to stimulate innovative thinking and celebrate great ideas will be a new competitive event at the annual meeting. Dubbed “CHEST FISH Bowl (Furthering Innovation and Science for Health),” this event will launch this month, with contestants submitting video applications that feature their great idea, and winners in selected categories to be selected at CHEST 2019 in New Orleans. CHEST Physician will be your source for information about all the CHEST Inspiration programs through a new series of articles called “CHEST Inspiration: Pacing the Future.”

As a leader in education for pulmonary, critical care, and sleep medicine, staying ahead of trends in its professional fields and across educational delivery, in general, is critical to remaining relevant and to best serve the membership. The leadership of the American College of Chest Physicians (CHEST) developed a multifaceted program this year entitled, “CHEST Inspiration,” a series of programmatic initiatives aimed at stimulating and encouraging innovation within the association and recognizing individuals with great ideas that streamline current processes or disrupt ways of traditional thinking about everyday problems.

The CHEST Board of Regents recently completed one of the first components of the CHEST Inspiration program – the 2019 CHEST Environmental Scan. This article describes the development of the 2019 CHEST Environmental Scan and its fit with the other components of CHEST Inspiration program.

Environmental scanning is a formal process for tracking trends and occurrences in an organization’s internal and external environment that bear on its success--currently and in the future. The environmental scanning process examines both quantitative and qualitative factors and identifies a set of key environmental indicators believed to have the most important impact on the organization’s work.

The 2019 CHEST Environmental Scan is a synthesis of work that took place in January 2019 at the CHEST Environmental Summit, a special joint session of the Board of Regents (BOR) and the CHEST Foundation Board of Trustees (BOT). In that session attendees attempted to free themselves from the usual concentrated focus on the College and Foundation missions, goals, and strategies, recognizing that a possible (even likely) unintended consequence of a narrow focus is losing sight of the outside world and the forces there that—like it or not—influence and could even disrupt the programs and strategies of CHEST and the CHEST Foundation.

To facilitate the process, CHEST engaged a market research and consulting agency with expertise in environmental scans and a client base of nonprofit organizations and associations. The consultant conducted secondary research organized around six drivers of change selected by CHEST leadership:

• Health Care

• Economy and Workforce

• Technology

• Education, Content Delivery, and Career Advancement

• Social, Political, Regulatory, and the Environment

• Philanthropy

The leadership had the opportunity to review the consultant’s research findings prior to the Environmental Summit. Then, in the in-person BOT/BOR summit meeting, the consultant’s research findings were discussed and debated and were addressed with the following questions:

• How will this trend impact members? How will it change their work environment and what they need to know?

• How will this trend impact CHEST? What are the challenges and opportunities?

• What responses or actions should CHEST take?

• Does this insight require changes to our strategic plan?

The consultant synthesized the debates and discussions and prepared a draft document that shaped this year’s document.

The 2019 CHEST Environmental Scan, which will be undated periodically, will be used to:

• Inform members about external developments and put each in perspective

• Help leadership and staff determine future directions and program opportunities

• Keep the 5-year strategic plan fresh and relevant

The environmental scan will be published in six monthly installments in CHEST Physician, with each installment addressing one of the drivers of change. Most of the content is confirming rather than revolutionary in nature. Each installment will be accompanied comments from one of four leading physician experts who will put the content into perspective.

The two other components of the CHEST Inspiration program are to engage a group of experts from outside the field of medicine and health care who are innovative and successful in their own professions. This focus group of professionals from outside of our association will be held in conjunction with the June Board of Regents meeting. An additional component to stimulate innovative thinking and celebrate great ideas will be a new competitive event at the annual meeting. Dubbed “CHEST FISH Bowl (Furthering Innovation and Science for Health),” this event will launch this month, with contestants submitting video applications that feature their great idea, and winners in selected categories to be selected at CHEST 2019 in New Orleans. CHEST Physician will be your source for information about all the CHEST Inspiration programs through a new series of articles called “CHEST Inspiration: Pacing the Future.”