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Nivolumab shows promise in early-stage resectable NSCLC
(NSCLC), according to the results of a 21-patient pilot trial.
Eighty percent of patients were alive and recurrence-free a year after surgery, said Patrick M. Forde, MBBCh, and his colleagues from Johns Hopkins University, Baltimore. The only grade 3 or higher adverse event was treatment-related pneumonia, which did not prevent surgery. The findings were reported at the annual meeting of the American Association for Cancer Research and simultaneously in the New England Journal of Medicine.
For the study (NCT02259621), 21 patients with treatment-naive, stage I, II, or III NSCLC received two preoperative doses of nivolumab (3 mg/kg) 2 weeks apart, with surgery timed for 4 weeks after the first dose. In all, 62% of patients had adenocarcinoma, 81% had stage II or IIIa disease, and 86% were current or former smokers. Patients were followed for a median of 12 months after surgery (range, 0.8-19.7 months), and the researchers assessed safety, tumor response, programmed death ligand 1 mutational burden, and T-cell response.
Among 20 patients with evaluable resected primary tumors, nine (45%) showed a major pathologic response, defined as having 10% or fewer residual viable tumor cells. Twelve-month, recurrence-free survival was 83% (95% confidence interval, 66%-100%). The three progressors included one patient with 75% residual tumor at resection who subsequently developed a brain lesion, a patient with 5% residual tumor at resection who developed mediastinal lymph node recurrence, and a patient with 80% residual tumor at resection. The first two patients had durable responses to stereotactic radiotherapy or chemoradiotherapy, while the third patient developed fatal distal metastatic disease.
Sequencing of 11 completely resected tumors linked major pathologic response with higher tumor mutational burden (P = .01). Mutational burden did not correlate with tumor programmed death ligand 1 expression. Deep sequencing of T-cell receptor–beta chain CDR3 regions also correlated major pathologic response with increased clonality of tumor-infiltrating T-cell clones that also expanded into peripheral blood. “Many of these clones were not detected in peripheral blood before treatment,” the investigators wrote.
In all, five (23%) patients developed treatment-related adverse events, and many developed more than one side effect. Grade 1-2 anorexia, taste distortion, vomiting, and diarrhea were most common, with isolated cases of grade 1-2 fever, infusion reaction, abdominal pain, abnormal liver function, dry skin, and delirium. The case of grade 3 pneumonia developed after the first dose of nivolumab. The patient stopped treatment and underwent uncomplicated surgical resection.
Funders included Cancer Research Institute–Stand Up 2 Cancer; Johns Hopkins Bloomberg–Kimmel Institute for Cancer Immunotherapy; Bristol-Myers Squibb; International Immuno-Oncology Network, LUNGevity Foundation; International Association for the Study of Lung Cancer; Lung Cancer Foundation of America; and numerous other foundations and universities. Bristol-Myers Squibb makes nivolumab and supplied the study drug. Dr. Forde disclosed study grant support from Bristol-Myers Squibb. He reported ties to Bristol-Myers Squibb, AbbVie, and other pharmaceutical companies outside the submitted work.
SOURCE: Forde PM. AACR Annual Meeting 2018. Forde PM et al. N Engl J Med. 2018 Apr 16. doi: 10.1056/NEJMoa1716078.
(NSCLC), according to the results of a 21-patient pilot trial.
Eighty percent of patients were alive and recurrence-free a year after surgery, said Patrick M. Forde, MBBCh, and his colleagues from Johns Hopkins University, Baltimore. The only grade 3 or higher adverse event was treatment-related pneumonia, which did not prevent surgery. The findings were reported at the annual meeting of the American Association for Cancer Research and simultaneously in the New England Journal of Medicine.
For the study (NCT02259621), 21 patients with treatment-naive, stage I, II, or III NSCLC received two preoperative doses of nivolumab (3 mg/kg) 2 weeks apart, with surgery timed for 4 weeks after the first dose. In all, 62% of patients had adenocarcinoma, 81% had stage II or IIIa disease, and 86% were current or former smokers. Patients were followed for a median of 12 months after surgery (range, 0.8-19.7 months), and the researchers assessed safety, tumor response, programmed death ligand 1 mutational burden, and T-cell response.
Among 20 patients with evaluable resected primary tumors, nine (45%) showed a major pathologic response, defined as having 10% or fewer residual viable tumor cells. Twelve-month, recurrence-free survival was 83% (95% confidence interval, 66%-100%). The three progressors included one patient with 75% residual tumor at resection who subsequently developed a brain lesion, a patient with 5% residual tumor at resection who developed mediastinal lymph node recurrence, and a patient with 80% residual tumor at resection. The first two patients had durable responses to stereotactic radiotherapy or chemoradiotherapy, while the third patient developed fatal distal metastatic disease.
Sequencing of 11 completely resected tumors linked major pathologic response with higher tumor mutational burden (P = .01). Mutational burden did not correlate with tumor programmed death ligand 1 expression. Deep sequencing of T-cell receptor–beta chain CDR3 regions also correlated major pathologic response with increased clonality of tumor-infiltrating T-cell clones that also expanded into peripheral blood. “Many of these clones were not detected in peripheral blood before treatment,” the investigators wrote.
In all, five (23%) patients developed treatment-related adverse events, and many developed more than one side effect. Grade 1-2 anorexia, taste distortion, vomiting, and diarrhea were most common, with isolated cases of grade 1-2 fever, infusion reaction, abdominal pain, abnormal liver function, dry skin, and delirium. The case of grade 3 pneumonia developed after the first dose of nivolumab. The patient stopped treatment and underwent uncomplicated surgical resection.
Funders included Cancer Research Institute–Stand Up 2 Cancer; Johns Hopkins Bloomberg–Kimmel Institute for Cancer Immunotherapy; Bristol-Myers Squibb; International Immuno-Oncology Network, LUNGevity Foundation; International Association for the Study of Lung Cancer; Lung Cancer Foundation of America; and numerous other foundations and universities. Bristol-Myers Squibb makes nivolumab and supplied the study drug. Dr. Forde disclosed study grant support from Bristol-Myers Squibb. He reported ties to Bristol-Myers Squibb, AbbVie, and other pharmaceutical companies outside the submitted work.
SOURCE: Forde PM. AACR Annual Meeting 2018. Forde PM et al. N Engl J Med. 2018 Apr 16. doi: 10.1056/NEJMoa1716078.
(NSCLC), according to the results of a 21-patient pilot trial.
Eighty percent of patients were alive and recurrence-free a year after surgery, said Patrick M. Forde, MBBCh, and his colleagues from Johns Hopkins University, Baltimore. The only grade 3 or higher adverse event was treatment-related pneumonia, which did not prevent surgery. The findings were reported at the annual meeting of the American Association for Cancer Research and simultaneously in the New England Journal of Medicine.
For the study (NCT02259621), 21 patients with treatment-naive, stage I, II, or III NSCLC received two preoperative doses of nivolumab (3 mg/kg) 2 weeks apart, with surgery timed for 4 weeks after the first dose. In all, 62% of patients had adenocarcinoma, 81% had stage II or IIIa disease, and 86% were current or former smokers. Patients were followed for a median of 12 months after surgery (range, 0.8-19.7 months), and the researchers assessed safety, tumor response, programmed death ligand 1 mutational burden, and T-cell response.
Among 20 patients with evaluable resected primary tumors, nine (45%) showed a major pathologic response, defined as having 10% or fewer residual viable tumor cells. Twelve-month, recurrence-free survival was 83% (95% confidence interval, 66%-100%). The three progressors included one patient with 75% residual tumor at resection who subsequently developed a brain lesion, a patient with 5% residual tumor at resection who developed mediastinal lymph node recurrence, and a patient with 80% residual tumor at resection. The first two patients had durable responses to stereotactic radiotherapy or chemoradiotherapy, while the third patient developed fatal distal metastatic disease.
Sequencing of 11 completely resected tumors linked major pathologic response with higher tumor mutational burden (P = .01). Mutational burden did not correlate with tumor programmed death ligand 1 expression. Deep sequencing of T-cell receptor–beta chain CDR3 regions also correlated major pathologic response with increased clonality of tumor-infiltrating T-cell clones that also expanded into peripheral blood. “Many of these clones were not detected in peripheral blood before treatment,” the investigators wrote.
In all, five (23%) patients developed treatment-related adverse events, and many developed more than one side effect. Grade 1-2 anorexia, taste distortion, vomiting, and diarrhea were most common, with isolated cases of grade 1-2 fever, infusion reaction, abdominal pain, abnormal liver function, dry skin, and delirium. The case of grade 3 pneumonia developed after the first dose of nivolumab. The patient stopped treatment and underwent uncomplicated surgical resection.
Funders included Cancer Research Institute–Stand Up 2 Cancer; Johns Hopkins Bloomberg–Kimmel Institute for Cancer Immunotherapy; Bristol-Myers Squibb; International Immuno-Oncology Network, LUNGevity Foundation; International Association for the Study of Lung Cancer; Lung Cancer Foundation of America; and numerous other foundations and universities. Bristol-Myers Squibb makes nivolumab and supplied the study drug. Dr. Forde disclosed study grant support from Bristol-Myers Squibb. He reported ties to Bristol-Myers Squibb, AbbVie, and other pharmaceutical companies outside the submitted work.
SOURCE: Forde PM. AACR Annual Meeting 2018. Forde PM et al. N Engl J Med. 2018 Apr 16. doi: 10.1056/NEJMoa1716078.
REPORTING FROM AACR ANNUAL MEETING
Key clinical point: Neoadjuvant nivolumab was tolerable and induced robust responses in resectable non–small cell lung cancers.
Major finding: In all, 45% of evaluable tumors showed a major pathological response. Eighty percent of resected patients were alive and recurrence-free a median of 12 months after surgery. One patient (5%) developed a grade 3 treatment-related adverse event.
Study details: Pilot study of 21 adults with early-stage resectable non–small cell lung cancer (NCT02259621).
Disclosures: Funders included Cancer Research Institute–Stand Up 2 Cancer; Johns Hopkins Bloomberg–Kimmel Institute for Cancer Immunotherapy; Bristol-Myers Squibb; International Immuno-Oncology Network, LUNGevity Foundation; International Association for the Study of Lung Cancer; Lung Cancer Foundation of America; and numerous other foundations and universities. Bristol-Myers Squibb makes nivolumab and supplied the study drug. Dr. Forde disclosed study grant support from Bristol-Myers Squibb. He reported ties to Bristol-Myers Squibb, AbbVie, and other pharmaceutical companies outside the submitted work.
Source: Forde PM. AACR Annual Meeting 2018. Forde PM et al. N Engl J Med. 2018 Apr 16. doi: 10.1056/NEJMoa1716078.
A Cluster of Idiopathic Pulmonary Fibrosis Cases
In 2016, a Virginia dentist who had been recently diagnosed with idiopathic pulmonary fibrosis (IPF) was being treated at a specialty clinic. The CDC was contacted to report concerns that IPF had been diagnosed in multiple dentists, also from Virginia, who had also sought treatment at the same specialty clinic.
CDC researchers reviewed medical records of 894 patients treated for IPF at the tertiary care center between 1996-2017. They found 8 patients were dentists and 1 was a dental technician. Seven of the patients had died.
Idiopathic pulmonary fibrosis is a chronic, progressive, fibrosing interstitial pneumonia. This is the first known described cluster of IPF among dental personnel, the CDC says. Although no clear etiology could be found, it is possible that occupational exposure contributed to the development of IPF. Viral infections, cigarette smoking, and exposure to dust, wood dust, and metal dust have been implicated. One of the surviving patients reported polishing dental appliances and preparing amalgams and impressions without respiratory protection, which could have exposed him to silica, alginate, and other compounds with known or potential respiratory toxicity.
The CDC researchers note that dental personnel are exposed to infectious agents, chemicals, airborne particulates, ionizing radiation, and other potentially hazardous materials. They cite the case of a dentist who died of respiratory failure. Postmortem analysis identified pneumoconiosis; examination of lung tissue revealed particles consistent with alginate impression powders.
Idiopathic pulmonary fibrosis has not previously been described among dental personnel, the researchers say. But when they queried the National Occupational Respiratory Mortality System for “other interstitial pulmonary diseases with fibrosis” listed as the underlying or contributing cause of death, they found 35 decedents categorized as having worked in dentists’ offices or as dentists. During 2016, dentists accounted for an estimated 0.038% of US residents, yet represented 0.893% of patients being treated for IPF at a tertiary care center—nearly a 23-fold difference. Those findings suggest, the researchers say, that a higher rate of IPF might occur among dental personnel than among the general population.
In 2016, a Virginia dentist who had been recently diagnosed with idiopathic pulmonary fibrosis (IPF) was being treated at a specialty clinic. The CDC was contacted to report concerns that IPF had been diagnosed in multiple dentists, also from Virginia, who had also sought treatment at the same specialty clinic.
CDC researchers reviewed medical records of 894 patients treated for IPF at the tertiary care center between 1996-2017. They found 8 patients were dentists and 1 was a dental technician. Seven of the patients had died.
Idiopathic pulmonary fibrosis is a chronic, progressive, fibrosing interstitial pneumonia. This is the first known described cluster of IPF among dental personnel, the CDC says. Although no clear etiology could be found, it is possible that occupational exposure contributed to the development of IPF. Viral infections, cigarette smoking, and exposure to dust, wood dust, and metal dust have been implicated. One of the surviving patients reported polishing dental appliances and preparing amalgams and impressions without respiratory protection, which could have exposed him to silica, alginate, and other compounds with known or potential respiratory toxicity.
The CDC researchers note that dental personnel are exposed to infectious agents, chemicals, airborne particulates, ionizing radiation, and other potentially hazardous materials. They cite the case of a dentist who died of respiratory failure. Postmortem analysis identified pneumoconiosis; examination of lung tissue revealed particles consistent with alginate impression powders.
Idiopathic pulmonary fibrosis has not previously been described among dental personnel, the researchers say. But when they queried the National Occupational Respiratory Mortality System for “other interstitial pulmonary diseases with fibrosis” listed as the underlying or contributing cause of death, they found 35 decedents categorized as having worked in dentists’ offices or as dentists. During 2016, dentists accounted for an estimated 0.038% of US residents, yet represented 0.893% of patients being treated for IPF at a tertiary care center—nearly a 23-fold difference. Those findings suggest, the researchers say, that a higher rate of IPF might occur among dental personnel than among the general population.
In 2016, a Virginia dentist who had been recently diagnosed with idiopathic pulmonary fibrosis (IPF) was being treated at a specialty clinic. The CDC was contacted to report concerns that IPF had been diagnosed in multiple dentists, also from Virginia, who had also sought treatment at the same specialty clinic.
CDC researchers reviewed medical records of 894 patients treated for IPF at the tertiary care center between 1996-2017. They found 8 patients were dentists and 1 was a dental technician. Seven of the patients had died.
Idiopathic pulmonary fibrosis is a chronic, progressive, fibrosing interstitial pneumonia. This is the first known described cluster of IPF among dental personnel, the CDC says. Although no clear etiology could be found, it is possible that occupational exposure contributed to the development of IPF. Viral infections, cigarette smoking, and exposure to dust, wood dust, and metal dust have been implicated. One of the surviving patients reported polishing dental appliances and preparing amalgams and impressions without respiratory protection, which could have exposed him to silica, alginate, and other compounds with known or potential respiratory toxicity.
The CDC researchers note that dental personnel are exposed to infectious agents, chemicals, airborne particulates, ionizing radiation, and other potentially hazardous materials. They cite the case of a dentist who died of respiratory failure. Postmortem analysis identified pneumoconiosis; examination of lung tissue revealed particles consistent with alginate impression powders.
Idiopathic pulmonary fibrosis has not previously been described among dental personnel, the researchers say. But when they queried the National Occupational Respiratory Mortality System for “other interstitial pulmonary diseases with fibrosis” listed as the underlying or contributing cause of death, they found 35 decedents categorized as having worked in dentists’ offices or as dentists. During 2016, dentists accounted for an estimated 0.038% of US residents, yet represented 0.893% of patients being treated for IPF at a tertiary care center—nearly a 23-fold difference. Those findings suggest, the researchers say, that a higher rate of IPF might occur among dental personnel than among the general population.
PDPK1 could be novel target in MCL
Researchers may have found a new therapeutic approach for treating mantle cell lymphoma (MCL) by targeting 3-phosphoinositide-dependent protein kinase 1 (PDPK1).
Saori Maegawa and colleagues at Kyoto Prefectural University of Medicine in Japan, evaluated PDPK1 activity in patient-derived primary B-cell lymphoma cells by immunohistochemical staining of p-PDPK1Ser241 (p-PDPK1) in tissue specimens from seven patients with MCL, six patients with diffuse large B-cell lymphoma, and five patients with follicular lymphoma. All specimens were biopsied at initial diagnosis, before starting treatment.
“Our study showed that PDPK1 inhibition caused inactivation of RSK2-NTKD, as well as the decrease of total RSK2 protein, but not of AKT, in MCL-derived cells,” the researchers wrote in Experimental Hematology. “This implies that RSK2 activity is mainly regulated by PDPK1 at both the transcriptional expression and post-translational levels, but AKT activity is regulated by a signaling pathway that does not interact with a PDPK1-mediated pathway in MCL.”
If a PDPK1 inhibitor is pursued as clinical target, the researchers said careful monitoring for hyperglycemia may be required since impaired glucose metabolism is commonly seen with AKT inhibitors. Future research in MCL could also be directed toward the targeting of RSK2-NTKD, the researchers wrote.
SOURCE: Maegawa S et al. Exp Hematol. 2018 Mar;59:72-81.e2.
Researchers may have found a new therapeutic approach for treating mantle cell lymphoma (MCL) by targeting 3-phosphoinositide-dependent protein kinase 1 (PDPK1).
Saori Maegawa and colleagues at Kyoto Prefectural University of Medicine in Japan, evaluated PDPK1 activity in patient-derived primary B-cell lymphoma cells by immunohistochemical staining of p-PDPK1Ser241 (p-PDPK1) in tissue specimens from seven patients with MCL, six patients with diffuse large B-cell lymphoma, and five patients with follicular lymphoma. All specimens were biopsied at initial diagnosis, before starting treatment.
“Our study showed that PDPK1 inhibition caused inactivation of RSK2-NTKD, as well as the decrease of total RSK2 protein, but not of AKT, in MCL-derived cells,” the researchers wrote in Experimental Hematology. “This implies that RSK2 activity is mainly regulated by PDPK1 at both the transcriptional expression and post-translational levels, but AKT activity is regulated by a signaling pathway that does not interact with a PDPK1-mediated pathway in MCL.”
If a PDPK1 inhibitor is pursued as clinical target, the researchers said careful monitoring for hyperglycemia may be required since impaired glucose metabolism is commonly seen with AKT inhibitors. Future research in MCL could also be directed toward the targeting of RSK2-NTKD, the researchers wrote.
SOURCE: Maegawa S et al. Exp Hematol. 2018 Mar;59:72-81.e2.
Researchers may have found a new therapeutic approach for treating mantle cell lymphoma (MCL) by targeting 3-phosphoinositide-dependent protein kinase 1 (PDPK1).
Saori Maegawa and colleagues at Kyoto Prefectural University of Medicine in Japan, evaluated PDPK1 activity in patient-derived primary B-cell lymphoma cells by immunohistochemical staining of p-PDPK1Ser241 (p-PDPK1) in tissue specimens from seven patients with MCL, six patients with diffuse large B-cell lymphoma, and five patients with follicular lymphoma. All specimens were biopsied at initial diagnosis, before starting treatment.
“Our study showed that PDPK1 inhibition caused inactivation of RSK2-NTKD, as well as the decrease of total RSK2 protein, but not of AKT, in MCL-derived cells,” the researchers wrote in Experimental Hematology. “This implies that RSK2 activity is mainly regulated by PDPK1 at both the transcriptional expression and post-translational levels, but AKT activity is regulated by a signaling pathway that does not interact with a PDPK1-mediated pathway in MCL.”
If a PDPK1 inhibitor is pursued as clinical target, the researchers said careful monitoring for hyperglycemia may be required since impaired glucose metabolism is commonly seen with AKT inhibitors. Future research in MCL could also be directed toward the targeting of RSK2-NTKD, the researchers wrote.
SOURCE: Maegawa S et al. Exp Hematol. 2018 Mar;59:72-81.e2.
FROM EXPERIMENTAL HEMATOLOGY
PrEP Prescriptions Are on the Rise
The CDC estimates that > 1.2 million people in the US could benefit from pre-exposure prophylaxis (PrEP). The National HIV/AIDS Strategy (NHAS) aims to increase the number of adults prescribed PrEP by at least 500% by 2020, or about 47,832 people.
So far, prescriptions for PrEP increased by > 300% between 2014 and 2015. In 2015, 33,273 people had been prescribed PrEP, triple the NHAS target for that year, says Richard Wolitski, PhD, director, Office of HIV/AIDS and Infectious Disease Policy.
But according to 1 study, only 10% of the new prescriptions were for African Americans and 12% for Latinos, even though in 2016 African Americans accounted for 44% of new HIV diagnoses and Latinos for 25%. By contrast, 74% of new prescriptions were written for whites who made up only 26% of new diagnoses in 2016.
Such disparities highlight the need to continue to monitor uptake and expand efforts to increase use of PrEP, Wolitski says in his blog for HIV.gov. Studies show that daily PrEP can reduce the risk of acquiring HIV via sex by > 90% and > 70% among injection drug users.
The NHAS has added a PrEP indicator as 1 of 3 developmental indicators, introduced in 2016. Wolitski advocates multiple strategies for HIV prevention, including policies, programs, education, and monitoring. But he emphasizes that preventing HIV is only one component of an individual’s overall health and well-being—it’s also necessary to address other “competing needs,” such as access to jobs and housing, coordinated systems of care, and collaborations with social services.
The CDC estimates that > 1.2 million people in the US could benefit from pre-exposure prophylaxis (PrEP). The National HIV/AIDS Strategy (NHAS) aims to increase the number of adults prescribed PrEP by at least 500% by 2020, or about 47,832 people.
So far, prescriptions for PrEP increased by > 300% between 2014 and 2015. In 2015, 33,273 people had been prescribed PrEP, triple the NHAS target for that year, says Richard Wolitski, PhD, director, Office of HIV/AIDS and Infectious Disease Policy.
But according to 1 study, only 10% of the new prescriptions were for African Americans and 12% for Latinos, even though in 2016 African Americans accounted for 44% of new HIV diagnoses and Latinos for 25%. By contrast, 74% of new prescriptions were written for whites who made up only 26% of new diagnoses in 2016.
Such disparities highlight the need to continue to monitor uptake and expand efforts to increase use of PrEP, Wolitski says in his blog for HIV.gov. Studies show that daily PrEP can reduce the risk of acquiring HIV via sex by > 90% and > 70% among injection drug users.
The NHAS has added a PrEP indicator as 1 of 3 developmental indicators, introduced in 2016. Wolitski advocates multiple strategies for HIV prevention, including policies, programs, education, and monitoring. But he emphasizes that preventing HIV is only one component of an individual’s overall health and well-being—it’s also necessary to address other “competing needs,” such as access to jobs and housing, coordinated systems of care, and collaborations with social services.
The CDC estimates that > 1.2 million people in the US could benefit from pre-exposure prophylaxis (PrEP). The National HIV/AIDS Strategy (NHAS) aims to increase the number of adults prescribed PrEP by at least 500% by 2020, or about 47,832 people.
So far, prescriptions for PrEP increased by > 300% between 2014 and 2015. In 2015, 33,273 people had been prescribed PrEP, triple the NHAS target for that year, says Richard Wolitski, PhD, director, Office of HIV/AIDS and Infectious Disease Policy.
But according to 1 study, only 10% of the new prescriptions were for African Americans and 12% for Latinos, even though in 2016 African Americans accounted for 44% of new HIV diagnoses and Latinos for 25%. By contrast, 74% of new prescriptions were written for whites who made up only 26% of new diagnoses in 2016.
Such disparities highlight the need to continue to monitor uptake and expand efforts to increase use of PrEP, Wolitski says in his blog for HIV.gov. Studies show that daily PrEP can reduce the risk of acquiring HIV via sex by > 90% and > 70% among injection drug users.
The NHAS has added a PrEP indicator as 1 of 3 developmental indicators, introduced in 2016. Wolitski advocates multiple strategies for HIV prevention, including policies, programs, education, and monitoring. But he emphasizes that preventing HIV is only one component of an individual’s overall health and well-being—it’s also necessary to address other “competing needs,” such as access to jobs and housing, coordinated systems of care, and collaborations with social services.
Studies Look at Monoclonal Antibodies for Resistant Infection
As more hospitalized patients develop infections that are immune to antibiotics, researchers are looking into new preventive therapies. National Institute of Allergy and Infectious-supported researchers are studying monoclonal antibodies and their effects on Pseudomonas aeruginosa (P aeruginosa) and Staphylococcus aureus (S aureus), which are among the antibiotic-resistant bacteria that the World Health Organization says pose the greatest risk to human health.
The monoclonal antibodies can be administered along with standard antibiotic therapy. Monoclonal antibodies have been used in cancer, Ebola, and respiratory syncytial virus but rarely have been used to target bacterial pathogens, National Institute of Health says.
One trial, EVADE, will evaluate the safety of the investigational medicine MEDI3902 and whether it can prevent pneumonia caused by P aeruginosa. The other study, SAATELLITE, will test the safety and efficacy of another investigational medicine, suvratoxumab, against S aureus. The researchers hope to enroll 30 patients from 15 intensive care units.
As more hospitalized patients develop infections that are immune to antibiotics, researchers are looking into new preventive therapies. National Institute of Allergy and Infectious-supported researchers are studying monoclonal antibodies and their effects on Pseudomonas aeruginosa (P aeruginosa) and Staphylococcus aureus (S aureus), which are among the antibiotic-resistant bacteria that the World Health Organization says pose the greatest risk to human health.
The monoclonal antibodies can be administered along with standard antibiotic therapy. Monoclonal antibodies have been used in cancer, Ebola, and respiratory syncytial virus but rarely have been used to target bacterial pathogens, National Institute of Health says.
One trial, EVADE, will evaluate the safety of the investigational medicine MEDI3902 and whether it can prevent pneumonia caused by P aeruginosa. The other study, SAATELLITE, will test the safety and efficacy of another investigational medicine, suvratoxumab, against S aureus. The researchers hope to enroll 30 patients from 15 intensive care units.
As more hospitalized patients develop infections that are immune to antibiotics, researchers are looking into new preventive therapies. National Institute of Allergy and Infectious-supported researchers are studying monoclonal antibodies and their effects on Pseudomonas aeruginosa (P aeruginosa) and Staphylococcus aureus (S aureus), which are among the antibiotic-resistant bacteria that the World Health Organization says pose the greatest risk to human health.
The monoclonal antibodies can be administered along with standard antibiotic therapy. Monoclonal antibodies have been used in cancer, Ebola, and respiratory syncytial virus but rarely have been used to target bacterial pathogens, National Institute of Health says.
One trial, EVADE, will evaluate the safety of the investigational medicine MEDI3902 and whether it can prevent pneumonia caused by P aeruginosa. The other study, SAATELLITE, will test the safety and efficacy of another investigational medicine, suvratoxumab, against S aureus. The researchers hope to enroll 30 patients from 15 intensive care units.
FDA grants priority review of follicular lymphoma drug
by the Food and Drug Administration.
The biopharmaceutical company Verastem is seeking full approval for duvelisib for the treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and accelerated approval for the treatment of relapsed/refractory follicular lymphoma. The FDA has set Oct. 5, 2018, as the target action date, according to Verastem.
by the Food and Drug Administration.
The biopharmaceutical company Verastem is seeking full approval for duvelisib for the treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and accelerated approval for the treatment of relapsed/refractory follicular lymphoma. The FDA has set Oct. 5, 2018, as the target action date, according to Verastem.
by the Food and Drug Administration.
The biopharmaceutical company Verastem is seeking full approval for duvelisib for the treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and accelerated approval for the treatment of relapsed/refractory follicular lymphoma. The FDA has set Oct. 5, 2018, as the target action date, according to Verastem.
Multidisciplinary teams improve diagnoses in ILD
New research provides strong statistical support for the use of dynamic multidisciplinary discussion in the diagnosis of patients who may have interstitial lung diseases (ILD).
and it changed the diagnosis in 41% of the other cases.
The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association adopted joint guidelines for the treatment of idiopathic pulmonary fibrosis in 2015, and the ATS and ERS updated guidelines for the classification and terminology for idiopathic interstitial pneumonias in 2013. The Lancet Respiratory Medicine published what some consider to be a landmark evaluation of multidisciplinary team agreement on diagnosis of interstitial lung disease following the adoption of these guidelines (Walsh SLF et al. 2016;4[7]:557-65). This study showed that in idiopathic pulmonary fibrosis, multidisciplinary team meetings “have a higher level of agreement on diagnoses, assign diagnoses with higher confidence more frequently, and provide diagnoses that have nonsignificant greater prognostic separation than do clinicians or radiologists in most cases,” the researchers wrote.
In the new study, MDD failed to produce a diagnosis or suggestions about a way forward in only 3.5% of patients, according to the study, which appeared March 30 in CHEST®.
According to Dr. Antin-Ozerkis, accurate diagnosis of ILD is crucial to treatment, but it can be challenging to achieve. The MDD approach has been recommended since 2002 by the ATS and ERS, she said.
The study authors, led by Laurens J. De Sadeleer, MD, of Belgium’s University Hospitals Leuven, define the MDD approach as one “in which expert ILD clinicians, radiologists, and pathologists integrate all available clinical data, laboratory results, high-resolution computed tomography [HRCT] findings, and lung biopsy [when performed].”
For the study, the researchers tracked pre-MDD and MDD diagnoses of 938 consecutive patients with possible ILD who were discussed during 2005-2015. Of these patients, referring physicians made preliminary diagnoses in 49% of cases; in the rest, physicians either failed to develop a diagnosis or offered multiple possible diagnoses.
MDD teams produced a change in diagnosis in 191 – 42% – of patients with a pre-MDD diagnosis. Another condition was diagnosed in 118 of these patients, and the MDD teams declined to classify the other 73 patients pending further investigation.
The MDD teams also were able to produce diagnoses in 80% of cases when referring physicians could not come up with diagnoses.
“Discrepancy between pre-MDD diagnosis before work-up and discussion was remarkable,” the study authors wrote, estimating that MDD added value for 70% of referred patients.
“We believe MDD should be a common practice in the diagnosis of every patient with suspected ILD,” the researchers said.
The study doesn’t examine the challenges of putting MDD into practice, but Dr. Antin-Ozerkis provided some perspective. “It may be difficult for physicians to take the time from a busy practice to meet with a multidisciplinary team. It can require resources to gather the data necessary to comprehensively assess each patient case. Additionally, maintaining staff with experienced pulmonologists, radiologists and pathologists may be costly.”
She added that “there are various ways in which MDD may occur,” and that the pros and cons of different methods have not been well studied. “This practice will likely evolve with the development of new biomarkers and other diagnostic strategies in IPF [idiopathic pulmonary fibrosis].”
Still, she said, “this joint undertaking is clearly vital in helping to guide clinical practice, including therapeutic decisions and discussion of prognosis. For now, any discussion between clinician, radiologist, and pathologist is of benefit.”
Research Foundation-Flanders and University Hospitals Leuven funded the study. Some study authors reported various disclosures. Dr. Antin-Ozerkis disclosed serving as an investigator on several clinical trials for IPF and other ILDs by Boehringer, Promedior, Fibrogen and Roche. She noted that payments go directly to the university with no direct payments to the investigator.
SOURCE: De Sadeleer LJ et al. Chest. 2018 Mar 30. doi: 10.1016/j.chest.2018.03.026.
MDD strategy is crucial for accurate ILD diagnoses
The field of interstitial lung diseases (ILD) is challenging, with more than 200 disorders as possible diagnoses for patients who present to clinicians with similar symptoms and chest x-ray findings. The multidisciplinary discussion (MDD) strategy is very important for attaining an accurate ILD diagnosis.
We have had routine, formal, multidisciplinary discussions at our center since 2008. My guesstimate is that at least a third of patients referred as having idiopathic pulmonary fibrosis or another form of ILD by pulmonologists had been given the wrong diagnosis. Frequently, this was because of incorrect impressions provided by local radiologists and/or pathologists along with the clinician’s own limited knowledge of ILD.
In my experience, some patients described their pulmonologists as becoming irate with them when they asked for a second opinion, and I have had to try to avoid confrontations with referring physicians when trying to explain why the referral diagnosis was inaccurate.
Challenges to instituting the multidisciplinary discussion approach include coverage by health plans for a second-opinion evaluation, the willingness of physicians (for example, pulmonologists) outside of academic referral centers to refer patients to a center capable of adequately conducting an MDD, and patients’ desire to undergo an evaluation at centers of excellence where an MDD can be performed.
One must have also adequate resources to perform a proper MDD. But even in centers that refer patients, pulmonologists should confer with their colleague radiologists – and pathologists when appropriate – to try to make the most accurate diagnosis. And they should continue to question their diagnosis at follow-up appointments, as new symptoms and findings may arise or additional crucial information can become available over time that can point to an alternative diagnosis.
Kenneth C. Meyer, MD, MS, served as medical director of the lung transplant program and head of ILD at the University of Wisconsin–Madison. He reported no relevant disclosures.
Second MDD may be helpful for CTD-related ILD
Accumulating evidence suggests that multidisciplinary committees play a central role in improving the diagnostic accuracy of complex medical conditions. Interstitial lung disease (ILD) encompasses a number of clinical entities and no single diagnostic test alone can discriminate among the various causes of ILD. Instead, these diagnoses are based on a constellation of signs and symptoms, and radiographic, pathologic, and laboratory studies.
However, unanswered questions remain. First, it is unclear whether a single MDD is sufficient. The present study found that 20% of cases were unclassifiable after the MDD. A second MDD may be helpful, especially in patients with ILDs related to connective tissue disease (CTD). The rheumatic diseases most commonly associated with ILD (for example, systemic sclerosis, rheumatoid arthritis, myositis) often evolve at different rates, and not all of the signs and symptoms of these conditions may be present or apparent at the time of the ILD presentation. A second MDD discussion may be particularly helpful in patients presenting with a specific CTD-related autoantibody in the absence of clinical signs and symptoms of a CTD. Another unanswered question is whether MDDs actually improve clinically meaningful outcomes for patients, such as survival and quality of life. At our CTD-ILD Program at the University of California, Los Angeles, we have found that our MDD has augmented patient satisfaction with their care, and it has also improved our ability to identify patients who are eligible for specific clinical studies. Future research is needed to determine to assess the impact of MDD on a variety of patient-centered and practice/research-focused outcomes.
Elizabeth Volkmann, MD, is founder and codirector of the CTD-ILD Program at the University of California, Los Angeles. She disclosed serving as a consultant or as a member of an advisory board for Boehringer Ingelheim and Astellas Pharma. She has received grants from Boehringer Ingelheim, Merck Serono, and the Rheumatology Research Foundation.
MDD strategy is crucial for accurate ILD diagnoses
The field of interstitial lung diseases (ILD) is challenging, with more than 200 disorders as possible diagnoses for patients who present to clinicians with similar symptoms and chest x-ray findings. The multidisciplinary discussion (MDD) strategy is very important for attaining an accurate ILD diagnosis.
We have had routine, formal, multidisciplinary discussions at our center since 2008. My guesstimate is that at least a third of patients referred as having idiopathic pulmonary fibrosis or another form of ILD by pulmonologists had been given the wrong diagnosis. Frequently, this was because of incorrect impressions provided by local radiologists and/or pathologists along with the clinician’s own limited knowledge of ILD.
In my experience, some patients described their pulmonologists as becoming irate with them when they asked for a second opinion, and I have had to try to avoid confrontations with referring physicians when trying to explain why the referral diagnosis was inaccurate.
Challenges to instituting the multidisciplinary discussion approach include coverage by health plans for a second-opinion evaluation, the willingness of physicians (for example, pulmonologists) outside of academic referral centers to refer patients to a center capable of adequately conducting an MDD, and patients’ desire to undergo an evaluation at centers of excellence where an MDD can be performed.
One must have also adequate resources to perform a proper MDD. But even in centers that refer patients, pulmonologists should confer with their colleague radiologists – and pathologists when appropriate – to try to make the most accurate diagnosis. And they should continue to question their diagnosis at follow-up appointments, as new symptoms and findings may arise or additional crucial information can become available over time that can point to an alternative diagnosis.
Kenneth C. Meyer, MD, MS, served as medical director of the lung transplant program and head of ILD at the University of Wisconsin–Madison. He reported no relevant disclosures.
Second MDD may be helpful for CTD-related ILD
Accumulating evidence suggests that multidisciplinary committees play a central role in improving the diagnostic accuracy of complex medical conditions. Interstitial lung disease (ILD) encompasses a number of clinical entities and no single diagnostic test alone can discriminate among the various causes of ILD. Instead, these diagnoses are based on a constellation of signs and symptoms, and radiographic, pathologic, and laboratory studies.
However, unanswered questions remain. First, it is unclear whether a single MDD is sufficient. The present study found that 20% of cases were unclassifiable after the MDD. A second MDD may be helpful, especially in patients with ILDs related to connective tissue disease (CTD). The rheumatic diseases most commonly associated with ILD (for example, systemic sclerosis, rheumatoid arthritis, myositis) often evolve at different rates, and not all of the signs and symptoms of these conditions may be present or apparent at the time of the ILD presentation. A second MDD discussion may be particularly helpful in patients presenting with a specific CTD-related autoantibody in the absence of clinical signs and symptoms of a CTD. Another unanswered question is whether MDDs actually improve clinically meaningful outcomes for patients, such as survival and quality of life. At our CTD-ILD Program at the University of California, Los Angeles, we have found that our MDD has augmented patient satisfaction with their care, and it has also improved our ability to identify patients who are eligible for specific clinical studies. Future research is needed to determine to assess the impact of MDD on a variety of patient-centered and practice/research-focused outcomes.
Elizabeth Volkmann, MD, is founder and codirector of the CTD-ILD Program at the University of California, Los Angeles. She disclosed serving as a consultant or as a member of an advisory board for Boehringer Ingelheim and Astellas Pharma. She has received grants from Boehringer Ingelheim, Merck Serono, and the Rheumatology Research Foundation.
MDD strategy is crucial for accurate ILD diagnoses
The field of interstitial lung diseases (ILD) is challenging, with more than 200 disorders as possible diagnoses for patients who present to clinicians with similar symptoms and chest x-ray findings. The multidisciplinary discussion (MDD) strategy is very important for attaining an accurate ILD diagnosis.
We have had routine, formal, multidisciplinary discussions at our center since 2008. My guesstimate is that at least a third of patients referred as having idiopathic pulmonary fibrosis or another form of ILD by pulmonologists had been given the wrong diagnosis. Frequently, this was because of incorrect impressions provided by local radiologists and/or pathologists along with the clinician’s own limited knowledge of ILD.
In my experience, some patients described their pulmonologists as becoming irate with them when they asked for a second opinion, and I have had to try to avoid confrontations with referring physicians when trying to explain why the referral diagnosis was inaccurate.
Challenges to instituting the multidisciplinary discussion approach include coverage by health plans for a second-opinion evaluation, the willingness of physicians (for example, pulmonologists) outside of academic referral centers to refer patients to a center capable of adequately conducting an MDD, and patients’ desire to undergo an evaluation at centers of excellence where an MDD can be performed.
One must have also adequate resources to perform a proper MDD. But even in centers that refer patients, pulmonologists should confer with their colleague radiologists – and pathologists when appropriate – to try to make the most accurate diagnosis. And they should continue to question their diagnosis at follow-up appointments, as new symptoms and findings may arise or additional crucial information can become available over time that can point to an alternative diagnosis.
Kenneth C. Meyer, MD, MS, served as medical director of the lung transplant program and head of ILD at the University of Wisconsin–Madison. He reported no relevant disclosures.
Second MDD may be helpful for CTD-related ILD
Accumulating evidence suggests that multidisciplinary committees play a central role in improving the diagnostic accuracy of complex medical conditions. Interstitial lung disease (ILD) encompasses a number of clinical entities and no single diagnostic test alone can discriminate among the various causes of ILD. Instead, these diagnoses are based on a constellation of signs and symptoms, and radiographic, pathologic, and laboratory studies.
However, unanswered questions remain. First, it is unclear whether a single MDD is sufficient. The present study found that 20% of cases were unclassifiable after the MDD. A second MDD may be helpful, especially in patients with ILDs related to connective tissue disease (CTD). The rheumatic diseases most commonly associated with ILD (for example, systemic sclerosis, rheumatoid arthritis, myositis) often evolve at different rates, and not all of the signs and symptoms of these conditions may be present or apparent at the time of the ILD presentation. A second MDD discussion may be particularly helpful in patients presenting with a specific CTD-related autoantibody in the absence of clinical signs and symptoms of a CTD. Another unanswered question is whether MDDs actually improve clinically meaningful outcomes for patients, such as survival and quality of life. At our CTD-ILD Program at the University of California, Los Angeles, we have found that our MDD has augmented patient satisfaction with their care, and it has also improved our ability to identify patients who are eligible for specific clinical studies. Future research is needed to determine to assess the impact of MDD on a variety of patient-centered and practice/research-focused outcomes.
Elizabeth Volkmann, MD, is founder and codirector of the CTD-ILD Program at the University of California, Los Angeles. She disclosed serving as a consultant or as a member of an advisory board for Boehringer Ingelheim and Astellas Pharma. She has received grants from Boehringer Ingelheim, Merck Serono, and the Rheumatology Research Foundation.
New research provides strong statistical support for the use of dynamic multidisciplinary discussion in the diagnosis of patients who may have interstitial lung diseases (ILD).
and it changed the diagnosis in 41% of the other cases.
The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association adopted joint guidelines for the treatment of idiopathic pulmonary fibrosis in 2015, and the ATS and ERS updated guidelines for the classification and terminology for idiopathic interstitial pneumonias in 2013. The Lancet Respiratory Medicine published what some consider to be a landmark evaluation of multidisciplinary team agreement on diagnosis of interstitial lung disease following the adoption of these guidelines (Walsh SLF et al. 2016;4[7]:557-65). This study showed that in idiopathic pulmonary fibrosis, multidisciplinary team meetings “have a higher level of agreement on diagnoses, assign diagnoses with higher confidence more frequently, and provide diagnoses that have nonsignificant greater prognostic separation than do clinicians or radiologists in most cases,” the researchers wrote.
In the new study, MDD failed to produce a diagnosis or suggestions about a way forward in only 3.5% of patients, according to the study, which appeared March 30 in CHEST®.
According to Dr. Antin-Ozerkis, accurate diagnosis of ILD is crucial to treatment, but it can be challenging to achieve. The MDD approach has been recommended since 2002 by the ATS and ERS, she said.
The study authors, led by Laurens J. De Sadeleer, MD, of Belgium’s University Hospitals Leuven, define the MDD approach as one “in which expert ILD clinicians, radiologists, and pathologists integrate all available clinical data, laboratory results, high-resolution computed tomography [HRCT] findings, and lung biopsy [when performed].”
For the study, the researchers tracked pre-MDD and MDD diagnoses of 938 consecutive patients with possible ILD who were discussed during 2005-2015. Of these patients, referring physicians made preliminary diagnoses in 49% of cases; in the rest, physicians either failed to develop a diagnosis or offered multiple possible diagnoses.
MDD teams produced a change in diagnosis in 191 – 42% – of patients with a pre-MDD diagnosis. Another condition was diagnosed in 118 of these patients, and the MDD teams declined to classify the other 73 patients pending further investigation.
The MDD teams also were able to produce diagnoses in 80% of cases when referring physicians could not come up with diagnoses.
“Discrepancy between pre-MDD diagnosis before work-up and discussion was remarkable,” the study authors wrote, estimating that MDD added value for 70% of referred patients.
“We believe MDD should be a common practice in the diagnosis of every patient with suspected ILD,” the researchers said.
The study doesn’t examine the challenges of putting MDD into practice, but Dr. Antin-Ozerkis provided some perspective. “It may be difficult for physicians to take the time from a busy practice to meet with a multidisciplinary team. It can require resources to gather the data necessary to comprehensively assess each patient case. Additionally, maintaining staff with experienced pulmonologists, radiologists and pathologists may be costly.”
She added that “there are various ways in which MDD may occur,” and that the pros and cons of different methods have not been well studied. “This practice will likely evolve with the development of new biomarkers and other diagnostic strategies in IPF [idiopathic pulmonary fibrosis].”
Still, she said, “this joint undertaking is clearly vital in helping to guide clinical practice, including therapeutic decisions and discussion of prognosis. For now, any discussion between clinician, radiologist, and pathologist is of benefit.”
Research Foundation-Flanders and University Hospitals Leuven funded the study. Some study authors reported various disclosures. Dr. Antin-Ozerkis disclosed serving as an investigator on several clinical trials for IPF and other ILDs by Boehringer, Promedior, Fibrogen and Roche. She noted that payments go directly to the university with no direct payments to the investigator.
SOURCE: De Sadeleer LJ et al. Chest. 2018 Mar 30. doi: 10.1016/j.chest.2018.03.026.
New research provides strong statistical support for the use of dynamic multidisciplinary discussion in the diagnosis of patients who may have interstitial lung diseases (ILD).
and it changed the diagnosis in 41% of the other cases.
The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association adopted joint guidelines for the treatment of idiopathic pulmonary fibrosis in 2015, and the ATS and ERS updated guidelines for the classification and terminology for idiopathic interstitial pneumonias in 2013. The Lancet Respiratory Medicine published what some consider to be a landmark evaluation of multidisciplinary team agreement on diagnosis of interstitial lung disease following the adoption of these guidelines (Walsh SLF et al. 2016;4[7]:557-65). This study showed that in idiopathic pulmonary fibrosis, multidisciplinary team meetings “have a higher level of agreement on diagnoses, assign diagnoses with higher confidence more frequently, and provide diagnoses that have nonsignificant greater prognostic separation than do clinicians or radiologists in most cases,” the researchers wrote.
In the new study, MDD failed to produce a diagnosis or suggestions about a way forward in only 3.5% of patients, according to the study, which appeared March 30 in CHEST®.
According to Dr. Antin-Ozerkis, accurate diagnosis of ILD is crucial to treatment, but it can be challenging to achieve. The MDD approach has been recommended since 2002 by the ATS and ERS, she said.
The study authors, led by Laurens J. De Sadeleer, MD, of Belgium’s University Hospitals Leuven, define the MDD approach as one “in which expert ILD clinicians, radiologists, and pathologists integrate all available clinical data, laboratory results, high-resolution computed tomography [HRCT] findings, and lung biopsy [when performed].”
For the study, the researchers tracked pre-MDD and MDD diagnoses of 938 consecutive patients with possible ILD who were discussed during 2005-2015. Of these patients, referring physicians made preliminary diagnoses in 49% of cases; in the rest, physicians either failed to develop a diagnosis or offered multiple possible diagnoses.
MDD teams produced a change in diagnosis in 191 – 42% – of patients with a pre-MDD diagnosis. Another condition was diagnosed in 118 of these patients, and the MDD teams declined to classify the other 73 patients pending further investigation.
The MDD teams also were able to produce diagnoses in 80% of cases when referring physicians could not come up with diagnoses.
“Discrepancy between pre-MDD diagnosis before work-up and discussion was remarkable,” the study authors wrote, estimating that MDD added value for 70% of referred patients.
“We believe MDD should be a common practice in the diagnosis of every patient with suspected ILD,” the researchers said.
The study doesn’t examine the challenges of putting MDD into practice, but Dr. Antin-Ozerkis provided some perspective. “It may be difficult for physicians to take the time from a busy practice to meet with a multidisciplinary team. It can require resources to gather the data necessary to comprehensively assess each patient case. Additionally, maintaining staff with experienced pulmonologists, radiologists and pathologists may be costly.”
She added that “there are various ways in which MDD may occur,” and that the pros and cons of different methods have not been well studied. “This practice will likely evolve with the development of new biomarkers and other diagnostic strategies in IPF [idiopathic pulmonary fibrosis].”
Still, she said, “this joint undertaking is clearly vital in helping to guide clinical practice, including therapeutic decisions and discussion of prognosis. For now, any discussion between clinician, radiologist, and pathologist is of benefit.”
Research Foundation-Flanders and University Hospitals Leuven funded the study. Some study authors reported various disclosures. Dr. Antin-Ozerkis disclosed serving as an investigator on several clinical trials for IPF and other ILDs by Boehringer, Promedior, Fibrogen and Roche. She noted that payments go directly to the university with no direct payments to the investigator.
SOURCE: De Sadeleer LJ et al. Chest. 2018 Mar 30. doi: 10.1016/j.chest.2018.03.026.
FROM CHEST
Key clinical point: Multidisciplinary discussion (MDD) in cases of suspected interstitial lung disease frequently produces adjustments of previous diagnoses and new diagnoses when none existed previously.
Major finding: MDD teams produced a change in diagnosis in 42% of patients with a pre-MDD diagnosis and in 80% of those without one.
Study details: 938 consecutive patients at University Hospitals Leuven, Belgium, with possible ILD who underwent MDD diagnostics during 2005-2015.
Disclosures: Research Foundation–Flanders and University Hospitals Leuven funded the study. Some study authors reported various disclosures. Dr. Antin-Ozerkis disclosed serving as an investigator on several clinical trials for idiopathic pulmonary fibrosis and other ILDs by Boehringer, Promedior, FibroGen, and Roche. She noted that payments go directly to the university, with no direct payments to the investigator.
Source: De Sadeleer LJ et al. Chest 2018. 2018 Mar 30. doi: 10.1016/j.chest.2018.03.026.
Asthma flourishing in its medical home
according to the Centers for Disease Control and Prevention.
Current asthma prevalence was 8.8% for adults aged 18 years and older who worked in health care and social assistance in 2011-2016, which put them above those in education services (8.2%); arts, entertainment, and recreation (8.1%); accommodation and food services (7.7%); and finance and insurance (7.5%). The overall rate for all working adults was 6.8%, Jacek M. Mazurek, MD, PhD, and Girija Syamlal, MBBS, reported in the Morbidity and Mortality Weekly Report.
Among persons with asthma who were employed in health care and social assistance, 45.8% reported having at least one asthma attack in the previous year. Among the subgroups of the industry, those working in hospitals were highest with a 51.7% rate of past-year asthma attacks, followed by those working in nursing and residential care facilities at 45.2%, those working in ambulatory health care services at 43.2%, and those working in social assistance at 42.9%. The highest asthma attack rates among all industries were 57.3% for wood product manufacturing and 56.7% for plastics and rubber products manufacturing, the investigators said, based on data from the National Health Interview Survey.
Asthma-related visits to the emergency department in the past year were much less common for those in health care – 11.3% overall – and followed a pattern different from asthma attacks. Those working in nursing and residential care facilities were highest at 13.8%, with those in social assistance at 12.3%, those in ambulatory care at 10.5%, and those in hospitals the lowest at 10.1%. The highest ED-visit rate for any industry, 22.9%, was for workers in private households, said Dr. Mazurek and Dr. Syamlal, both of the respiratory health division at the CDC’s National Institute for Occupational Safety and Health in Morgantown, W.Va.
SOURCE: Mazurek JM, Syamlal G. MMWR. 2018 Apr 6;67(13):377-86.
according to the Centers for Disease Control and Prevention.
Current asthma prevalence was 8.8% for adults aged 18 years and older who worked in health care and social assistance in 2011-2016, which put them above those in education services (8.2%); arts, entertainment, and recreation (8.1%); accommodation and food services (7.7%); and finance and insurance (7.5%). The overall rate for all working adults was 6.8%, Jacek M. Mazurek, MD, PhD, and Girija Syamlal, MBBS, reported in the Morbidity and Mortality Weekly Report.
Among persons with asthma who were employed in health care and social assistance, 45.8% reported having at least one asthma attack in the previous year. Among the subgroups of the industry, those working in hospitals were highest with a 51.7% rate of past-year asthma attacks, followed by those working in nursing and residential care facilities at 45.2%, those working in ambulatory health care services at 43.2%, and those working in social assistance at 42.9%. The highest asthma attack rates among all industries were 57.3% for wood product manufacturing and 56.7% for plastics and rubber products manufacturing, the investigators said, based on data from the National Health Interview Survey.
Asthma-related visits to the emergency department in the past year were much less common for those in health care – 11.3% overall – and followed a pattern different from asthma attacks. Those working in nursing and residential care facilities were highest at 13.8%, with those in social assistance at 12.3%, those in ambulatory care at 10.5%, and those in hospitals the lowest at 10.1%. The highest ED-visit rate for any industry, 22.9%, was for workers in private households, said Dr. Mazurek and Dr. Syamlal, both of the respiratory health division at the CDC’s National Institute for Occupational Safety and Health in Morgantown, W.Va.
SOURCE: Mazurek JM, Syamlal G. MMWR. 2018 Apr 6;67(13):377-86.
according to the Centers for Disease Control and Prevention.
Current asthma prevalence was 8.8% for adults aged 18 years and older who worked in health care and social assistance in 2011-2016, which put them above those in education services (8.2%); arts, entertainment, and recreation (8.1%); accommodation and food services (7.7%); and finance and insurance (7.5%). The overall rate for all working adults was 6.8%, Jacek M. Mazurek, MD, PhD, and Girija Syamlal, MBBS, reported in the Morbidity and Mortality Weekly Report.
Among persons with asthma who were employed in health care and social assistance, 45.8% reported having at least one asthma attack in the previous year. Among the subgroups of the industry, those working in hospitals were highest with a 51.7% rate of past-year asthma attacks, followed by those working in nursing and residential care facilities at 45.2%, those working in ambulatory health care services at 43.2%, and those working in social assistance at 42.9%. The highest asthma attack rates among all industries were 57.3% for wood product manufacturing and 56.7% for plastics and rubber products manufacturing, the investigators said, based on data from the National Health Interview Survey.
Asthma-related visits to the emergency department in the past year were much less common for those in health care – 11.3% overall – and followed a pattern different from asthma attacks. Those working in nursing and residential care facilities were highest at 13.8%, with those in social assistance at 12.3%, those in ambulatory care at 10.5%, and those in hospitals the lowest at 10.1%. The highest ED-visit rate for any industry, 22.9%, was for workers in private households, said Dr. Mazurek and Dr. Syamlal, both of the respiratory health division at the CDC’s National Institute for Occupational Safety and Health in Morgantown, W.Va.
SOURCE: Mazurek JM, Syamlal G. MMWR. 2018 Apr 6;67(13):377-86.
FROM MMWR
EAGLES: Smoking cessation therapy did not up cardiovascular risk
among stable adult smokers with up to one year of follow-up.
“In what we believe to be the largest smoking cessation clinical trial and the only trial comparing NRT, bupropion, and varenicline [with] placebo, we found no signal that smoking cessation pharmacotherapy increases the risk of serious cardiovascular disease or cardiovascular adverse events in a general population of smokers,” concluded Neal L. Benowitz, MD, of the University of California, San Francisco, and his associates. “While the number of events was small, the incidence of serious cardiovascular events was low, suggesting that any absolute increase in risk that we might have missed would be low and not clinically meaningful.” The findings were reported online April 9 in JAMA Internal Medicine.
In this double-blind, multicenter, triple-dummy trial (EAGLES), Dr. Benowitz and his associates randomly assigned 8,058 adult smokers, who did not have acute or unstable cardiovascular disease, to receive bupropion (150 mg twice daily), varenicline (1 mg twice daily), NRT (21-mg/day patch with tapering), or placebo for 12 weeks, followed by 12 weeks of follow-up. A total of 4,595 patients agreed to be followed for another 28 weeks during an extension phase of the trial. More than half of the patients were women and the average age of a participant was 47 years. The primary endpoint was time to major adverse cardiovascular event (MACE), including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The researchers selected time to MACE as their primary endpoint to better detect differences among groups. One of the secondary end points was the occurrence of MACEs over the same 3 time intervals. Additionally, cardiovascular deaths, nonfatal MI, and nonfatal stroke (the components of MACE) were evaluated individually, as were hospitalizations for congestive heart failure and serious arrhythmias.
Differences in time to onset of MACE between all four patient groups, were not significant. The overall incidence of MACEs was less than 0.5% during all observation periods. There were also no significant differences in rates of the individual types of MACE, coronary revascularization, hospitalization for unstable angina, or new or worsening peripheral vascular disease requiring treatment among groups. Changes in body weight, blood pressure, and heart rate also were similar across patients.
There were five cardiovascular deaths, including one in the varenicline group, two in the bupropion group and two in the placebo group, according to the researchers. Overall the trial results “are consistent with and support previously published findings from meta-analyses and small clinical trials in smokers with known [cardiovascular disease],” they wrote.
GlaxoSmithKline and Pfizer, who make and market smoking cessation therapies, sponsored the study. Dr. Benowitz disclosed a consulting relationship with Pfizer and other pharmaceutical companies. He also has been a paid expert witness in litigation against tobacco companies. Eight coinvestigators disclosed ties to Pfizer, GlaxoSmithKline, and other companies.
SOURCE: Benowitz NL et al. JAMA Intern Med. 2018 Apr 9. doi: 10.1001/jamainternmed.2018.0397)
among stable adult smokers with up to one year of follow-up.
“In what we believe to be the largest smoking cessation clinical trial and the only trial comparing NRT, bupropion, and varenicline [with] placebo, we found no signal that smoking cessation pharmacotherapy increases the risk of serious cardiovascular disease or cardiovascular adverse events in a general population of smokers,” concluded Neal L. Benowitz, MD, of the University of California, San Francisco, and his associates. “While the number of events was small, the incidence of serious cardiovascular events was low, suggesting that any absolute increase in risk that we might have missed would be low and not clinically meaningful.” The findings were reported online April 9 in JAMA Internal Medicine.
In this double-blind, multicenter, triple-dummy trial (EAGLES), Dr. Benowitz and his associates randomly assigned 8,058 adult smokers, who did not have acute or unstable cardiovascular disease, to receive bupropion (150 mg twice daily), varenicline (1 mg twice daily), NRT (21-mg/day patch with tapering), or placebo for 12 weeks, followed by 12 weeks of follow-up. A total of 4,595 patients agreed to be followed for another 28 weeks during an extension phase of the trial. More than half of the patients were women and the average age of a participant was 47 years. The primary endpoint was time to major adverse cardiovascular event (MACE), including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The researchers selected time to MACE as their primary endpoint to better detect differences among groups. One of the secondary end points was the occurrence of MACEs over the same 3 time intervals. Additionally, cardiovascular deaths, nonfatal MI, and nonfatal stroke (the components of MACE) were evaluated individually, as were hospitalizations for congestive heart failure and serious arrhythmias.
Differences in time to onset of MACE between all four patient groups, were not significant. The overall incidence of MACEs was less than 0.5% during all observation periods. There were also no significant differences in rates of the individual types of MACE, coronary revascularization, hospitalization for unstable angina, or new or worsening peripheral vascular disease requiring treatment among groups. Changes in body weight, blood pressure, and heart rate also were similar across patients.
There were five cardiovascular deaths, including one in the varenicline group, two in the bupropion group and two in the placebo group, according to the researchers. Overall the trial results “are consistent with and support previously published findings from meta-analyses and small clinical trials in smokers with known [cardiovascular disease],” they wrote.
GlaxoSmithKline and Pfizer, who make and market smoking cessation therapies, sponsored the study. Dr. Benowitz disclosed a consulting relationship with Pfizer and other pharmaceutical companies. He also has been a paid expert witness in litigation against tobacco companies. Eight coinvestigators disclosed ties to Pfizer, GlaxoSmithKline, and other companies.
SOURCE: Benowitz NL et al. JAMA Intern Med. 2018 Apr 9. doi: 10.1001/jamainternmed.2018.0397)
among stable adult smokers with up to one year of follow-up.
“In what we believe to be the largest smoking cessation clinical trial and the only trial comparing NRT, bupropion, and varenicline [with] placebo, we found no signal that smoking cessation pharmacotherapy increases the risk of serious cardiovascular disease or cardiovascular adverse events in a general population of smokers,” concluded Neal L. Benowitz, MD, of the University of California, San Francisco, and his associates. “While the number of events was small, the incidence of serious cardiovascular events was low, suggesting that any absolute increase in risk that we might have missed would be low and not clinically meaningful.” The findings were reported online April 9 in JAMA Internal Medicine.
In this double-blind, multicenter, triple-dummy trial (EAGLES), Dr. Benowitz and his associates randomly assigned 8,058 adult smokers, who did not have acute or unstable cardiovascular disease, to receive bupropion (150 mg twice daily), varenicline (1 mg twice daily), NRT (21-mg/day patch with tapering), or placebo for 12 weeks, followed by 12 weeks of follow-up. A total of 4,595 patients agreed to be followed for another 28 weeks during an extension phase of the trial. More than half of the patients were women and the average age of a participant was 47 years. The primary endpoint was time to major adverse cardiovascular event (MACE), including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The researchers selected time to MACE as their primary endpoint to better detect differences among groups. One of the secondary end points was the occurrence of MACEs over the same 3 time intervals. Additionally, cardiovascular deaths, nonfatal MI, and nonfatal stroke (the components of MACE) were evaluated individually, as were hospitalizations for congestive heart failure and serious arrhythmias.
Differences in time to onset of MACE between all four patient groups, were not significant. The overall incidence of MACEs was less than 0.5% during all observation periods. There were also no significant differences in rates of the individual types of MACE, coronary revascularization, hospitalization for unstable angina, or new or worsening peripheral vascular disease requiring treatment among groups. Changes in body weight, blood pressure, and heart rate also were similar across patients.
There were five cardiovascular deaths, including one in the varenicline group, two in the bupropion group and two in the placebo group, according to the researchers. Overall the trial results “are consistent with and support previously published findings from meta-analyses and small clinical trials in smokers with known [cardiovascular disease],” they wrote.
GlaxoSmithKline and Pfizer, who make and market smoking cessation therapies, sponsored the study. Dr. Benowitz disclosed a consulting relationship with Pfizer and other pharmaceutical companies. He also has been a paid expert witness in litigation against tobacco companies. Eight coinvestigators disclosed ties to Pfizer, GlaxoSmithKline, and other companies.
SOURCE: Benowitz NL et al. JAMA Intern Med. 2018 Apr 9. doi: 10.1001/jamainternmed.2018.0397)
FROM JAMA INTERNAL MEDICINE
Key clinical point: The use of smoking cessation therapy did not increase the risk of cardiovascular events in adult smokers.
Major finding: There were no significant differences among groups in rates of major adverse cardiovascular events, rates of other pertinent cardiovascular events, time to cardiovascular events, blood pressure, or heart rate.
Study details: Double-blind, randomized, multicenter, triple-dummy trial of 8,058 adult smokers receiving nicotine replacement therapy, bupropion, varenicline, or placebo (EAGLES).
Disclosures: GlaxoSmithKline and Pfizer sponsored the study and make the drugs. Dr. Benowitz disclosed a consulting relationship with Pfizer and other pharmaceutical companies. He also has been a paid expert witness in litigation against tobacco companies. Eight coinvestigators disclosed ties to Pfizer, GlaxoSmithKline, and other companies.
Source: Benowitz NL et al. JAMA Intern Med. 2018 Apr 9. doi: 10.1001/jamainternmed.2018.0397.
The outcomes of “GOLD 2017”
After the Global Initiative for Chronic Obstructive Lung Disease released updated recommendations for grading COPD patients’ level of disease in November of 2016, Imran Iftikhar, MD, tried to incorporate them into his practice, but he encountered problems.
For one thing, the new classification system, which became known as GOLD 2017, uncoupled spirometry results from the ABCD treatment algorithm. “I found it wasn’t really helping me in terms of prognostication or COPD management,” said Dr. Iftikhar, section chief of pulmonary and critical care at Emory Saint Joseph’s Hospital, Atlanta. “Although the purpose of the GOLD classification was not really meant for prognostication, most practicing physicians are frequently asked about prognosis by patients, and I am not sure if the 2017 reclassification really helps with that.”
The GOLD 2017 classification simplified the chronic obstructive pulmonary disease staging that was available from 2011 to 2015 from three variables (spirometry thresholds, exacerbation risk, and dyspnea scale) to two variables (exacerbation risk and dyspnea scale). In the 2017 report, authors of the new guidelines characterized forced expiratory volume in 1 second (FEV1) as “a poor predictor of disease status” and proposed that clinicians derive ABCD groups exclusively from patient symptoms and their exacerbations. FEV1 is an “important parameter at the population level” in predicting hospitalization and mortality, the authors wrote, but keeping results separate “acknowledges the limitations of FEV1 in making treatment decisions for individualized patient care and highlights the importance of patient symptoms and exacerbation risks in guiding therapies in COPD.”
According to Meilan Han, MD, MS, a member of the GOLD Science Committee, since release of the 2017 guidelines, “clinicians have indicated that they like the flexibility the system provides in separating spirometry, symptoms, and exacerbation risk as this more accurately reflects the heterogeneity we see in the COPD patient population.” Nevertheless, how this approach influences long-term outcomes remains unclear.
Daniel Ouellette, MD, FCCP, a pulmonologist with the Henry Ford Health System in Detroit, described the GOLD 2017 criteria as “a good step forward” but said he wasn’t sure if the optimal or perfect tool exists for categorizing COPD patients’ level of disease.
“I think what we see is an effort to use all of these criteria to help us better treat our patients. I think ,” he said in an interview.
“All guidelines need to be modified as further research becomes available. I think that the frontiers of this area are going to be to incorporate new elements such as tobacco history, more emphasis on clinical signs and symptoms, and use of markers other than spirometry, such as eosinophil count, to categorize patients with COPD,” Dr. Ouellette added.
In an analysis of the GOLD 2017 criteria applied to 819 COPD patients in Spain and the United States, published online Nov. 3, 2017, in the American Journal of Respiratory and Critical Care Medicine, Carlos Cabrera López, MD, and his colleagues concluded that the mortality risk was better predicted by the 2015 GOLD classification system than by the 2017 iteration (Am J Respir Crit Care Med. 2018 Feb. doi: 10.101164/rccm.201707-1363OC).
The distribution of Charlson index scores also changed. Whereas group D was higher than B in 2015, they became similar in the 2017 system. For her part, Dr. Han emphasized that the primary goal of the GOLD ABCD classification system is to categorize patients with respect to treatment groups. “Current therapy targets symptoms and exacerbations, which are the key current elements of the classification schema,” she said in an interview. “The results of the Cabrera Lopez analysis are not necessarily unexpected, as FEV1 is associated with mortality.”
In a prospective, multicenter analysis, Portuguese researchers compared the performance of GOLD 2011 and 2017 in terms of how 200 COPD patients were reclassified, the level of agreement between the two iterations, and the performance of each to predict future exacerbations (COPD. 2018 Feb;15[1]; 21-6). They found that about half of patients classified as GOLD D under the 2011 guidelines became classified as GOLD B when the 2017 version was used, and the extent of agreement between the two iterations was moderate (P less than .001). They also found that the two versions of the guidelines were equivalently effective at predicting exacerbations (69.7% vs. 67.6% in the 2011 and 2017 iterations, respectively). In addition, patients who met the criteria for a GOLD B grouping in the 2017 iteration exacerbated 17% more often and had a lower percent predicted post bronchodilator FEV1 than did those who met the criteria for a GOLD B classification under the 2011 guidelines.
Dr. Han, who is also an associate professor of medicine at the University of Michigan Hospital, acknowledged that GOLD 2017 has resulted in the reclassification of some previously group D patients as group B patients. “Our primary goal is to aid clinicians with the diagnosis and management of patients with COPD,” she said. “We look forward to additional data coming in from ongoing clinical trials that will provide longer term data to further refine treatment algorithms.”
In a recent study of more than 33,000 Danish patients older than age 30 with COPD, researchers led by Anne Gedebjerg, MD, found that the GOLD 2017 ABCD classification did not predict all-cause and respiratory mortality more accurately than previous GOLD iterations from 2007 and 2011. Area under the curve for all-cause mortality was 0.61 for GOLD 2007, 0.61 for GOLD 2011, and 0.63 for GOLD 2017, while the area under the curve for respiratory mortality was 0.64 for GOLD 2007, 0.63 for GOLD 2011, and 0.65 for GOLD 2017 (Lancet Respir Med. 2018 Jan;6[3]:204-12).
However, when the spirometric stages 1-4 were combined with the A to D groupings based on symptoms and exacerbations, the 2017 classification predicted mortality with greater accuracy, compared with previous iterations (P less than .0001). “My practice is very much like this paper,” Dr. Iftikhar said. “I use both the spirometric grade and the ABCD grouping to specify which ‘group’ and ‘grade’ my patient belongs to. I think future investigators need to combine ABCD with spirometry classification to see how we can improve the classification system.”
In a commentary published in the same issue of the Lancet Respiratory Medicine as the large Danish study, Joan B. Soriano, MD, PhD, wrote that the 2011 GOLD guideline’s collapse of four spirometric thresholds (greater than 80%, 50%-80%, 30%-50%, and less than 30%) into just two (greater than 50% or 50% or less) “reduced the system’s ability to inform and predict mortality from the short term up to 10 years” (Lancet Respir Med. 2018 Jan;6[3]:165-6).
Lung function remains the best available biomarker for life expectancy in both patients with COPD and the general population,” wrote Dr. Soriano, a respiratory medicine researcher based in Madrid, Spain.
Additional important outcomes
Dr. Ouellette noted that while mortality is an important outcome for COPD patients, it’s not the only outcome of interest. “In addition to [trying to] help people live longer, which is certainly a desirable goal, we also want to make people be able to be more functional during their life, have fewer hospitalizations, and have less of a need of other types of supportive medical care for worsening of their disease,” he said. “The fact that the current guidelines don’t improve mortality more than the previous ones may not be a negative thing. It may tell us that the previous guidelines already did a pretty good job of helping us to improve mortality.”
Dr. Ouellette was quick to add that none of inhaled drugs currently available to treat COPD have been conclusively shown to improve mortality. “The only things we know that improve mortality for COPD patients are quitting smoking and using oxygen if a patient meets predefined goals for oxygen,” he said. “So the fact that GOLD criteria doesn’t improve mortality shouldn’t make us think that it’s not a useful tool. We already know that the medicines may not help people live longer.”
Dr. Han pointed out that spirometry “is still used to further clarify the choice of therapy recommended based on the nature and degree of airflow obstruction in light of severity of patient symptoms. The data are still designed to be used in conjunction to personalize therapy for patients.”
She added that the GOLD Science Committee “welcomes additional data analyses so that future recommendations can be further refined.”
Dr. Han disclosed that she has consulted for Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline. She has also received in-kind research support from Novartis and Sunovion.
Dr. Iftikhar reported having no financial disclosures. Dr. Ouellette is a member of CHEST® Physician’s editorial advisory board. He disclosed being part of a federally funded study being carried out by the Patient-Centered Outcomes Research Institute.
There was no industry involvement in the GOLD 2017 report, but many of its authors and board members had pharmaceutical company ties, and GOLD’s treatment advice relies on data from industry-sponsored studies.
After the Global Initiative for Chronic Obstructive Lung Disease released updated recommendations for grading COPD patients’ level of disease in November of 2016, Imran Iftikhar, MD, tried to incorporate them into his practice, but he encountered problems.
For one thing, the new classification system, which became known as GOLD 2017, uncoupled spirometry results from the ABCD treatment algorithm. “I found it wasn’t really helping me in terms of prognostication or COPD management,” said Dr. Iftikhar, section chief of pulmonary and critical care at Emory Saint Joseph’s Hospital, Atlanta. “Although the purpose of the GOLD classification was not really meant for prognostication, most practicing physicians are frequently asked about prognosis by patients, and I am not sure if the 2017 reclassification really helps with that.”
The GOLD 2017 classification simplified the chronic obstructive pulmonary disease staging that was available from 2011 to 2015 from three variables (spirometry thresholds, exacerbation risk, and dyspnea scale) to two variables (exacerbation risk and dyspnea scale). In the 2017 report, authors of the new guidelines characterized forced expiratory volume in 1 second (FEV1) as “a poor predictor of disease status” and proposed that clinicians derive ABCD groups exclusively from patient symptoms and their exacerbations. FEV1 is an “important parameter at the population level” in predicting hospitalization and mortality, the authors wrote, but keeping results separate “acknowledges the limitations of FEV1 in making treatment decisions for individualized patient care and highlights the importance of patient symptoms and exacerbation risks in guiding therapies in COPD.”
According to Meilan Han, MD, MS, a member of the GOLD Science Committee, since release of the 2017 guidelines, “clinicians have indicated that they like the flexibility the system provides in separating spirometry, symptoms, and exacerbation risk as this more accurately reflects the heterogeneity we see in the COPD patient population.” Nevertheless, how this approach influences long-term outcomes remains unclear.
Daniel Ouellette, MD, FCCP, a pulmonologist with the Henry Ford Health System in Detroit, described the GOLD 2017 criteria as “a good step forward” but said he wasn’t sure if the optimal or perfect tool exists for categorizing COPD patients’ level of disease.
“I think what we see is an effort to use all of these criteria to help us better treat our patients. I think ,” he said in an interview.
“All guidelines need to be modified as further research becomes available. I think that the frontiers of this area are going to be to incorporate new elements such as tobacco history, more emphasis on clinical signs and symptoms, and use of markers other than spirometry, such as eosinophil count, to categorize patients with COPD,” Dr. Ouellette added.
In an analysis of the GOLD 2017 criteria applied to 819 COPD patients in Spain and the United States, published online Nov. 3, 2017, in the American Journal of Respiratory and Critical Care Medicine, Carlos Cabrera López, MD, and his colleagues concluded that the mortality risk was better predicted by the 2015 GOLD classification system than by the 2017 iteration (Am J Respir Crit Care Med. 2018 Feb. doi: 10.101164/rccm.201707-1363OC).
The distribution of Charlson index scores also changed. Whereas group D was higher than B in 2015, they became similar in the 2017 system. For her part, Dr. Han emphasized that the primary goal of the GOLD ABCD classification system is to categorize patients with respect to treatment groups. “Current therapy targets symptoms and exacerbations, which are the key current elements of the classification schema,” she said in an interview. “The results of the Cabrera Lopez analysis are not necessarily unexpected, as FEV1 is associated with mortality.”
In a prospective, multicenter analysis, Portuguese researchers compared the performance of GOLD 2011 and 2017 in terms of how 200 COPD patients were reclassified, the level of agreement between the two iterations, and the performance of each to predict future exacerbations (COPD. 2018 Feb;15[1]; 21-6). They found that about half of patients classified as GOLD D under the 2011 guidelines became classified as GOLD B when the 2017 version was used, and the extent of agreement between the two iterations was moderate (P less than .001). They also found that the two versions of the guidelines were equivalently effective at predicting exacerbations (69.7% vs. 67.6% in the 2011 and 2017 iterations, respectively). In addition, patients who met the criteria for a GOLD B grouping in the 2017 iteration exacerbated 17% more often and had a lower percent predicted post bronchodilator FEV1 than did those who met the criteria for a GOLD B classification under the 2011 guidelines.
Dr. Han, who is also an associate professor of medicine at the University of Michigan Hospital, acknowledged that GOLD 2017 has resulted in the reclassification of some previously group D patients as group B patients. “Our primary goal is to aid clinicians with the diagnosis and management of patients with COPD,” she said. “We look forward to additional data coming in from ongoing clinical trials that will provide longer term data to further refine treatment algorithms.”
In a recent study of more than 33,000 Danish patients older than age 30 with COPD, researchers led by Anne Gedebjerg, MD, found that the GOLD 2017 ABCD classification did not predict all-cause and respiratory mortality more accurately than previous GOLD iterations from 2007 and 2011. Area under the curve for all-cause mortality was 0.61 for GOLD 2007, 0.61 for GOLD 2011, and 0.63 for GOLD 2017, while the area under the curve for respiratory mortality was 0.64 for GOLD 2007, 0.63 for GOLD 2011, and 0.65 for GOLD 2017 (Lancet Respir Med. 2018 Jan;6[3]:204-12).
However, when the spirometric stages 1-4 were combined with the A to D groupings based on symptoms and exacerbations, the 2017 classification predicted mortality with greater accuracy, compared with previous iterations (P less than .0001). “My practice is very much like this paper,” Dr. Iftikhar said. “I use both the spirometric grade and the ABCD grouping to specify which ‘group’ and ‘grade’ my patient belongs to. I think future investigators need to combine ABCD with spirometry classification to see how we can improve the classification system.”
In a commentary published in the same issue of the Lancet Respiratory Medicine as the large Danish study, Joan B. Soriano, MD, PhD, wrote that the 2011 GOLD guideline’s collapse of four spirometric thresholds (greater than 80%, 50%-80%, 30%-50%, and less than 30%) into just two (greater than 50% or 50% or less) “reduced the system’s ability to inform and predict mortality from the short term up to 10 years” (Lancet Respir Med. 2018 Jan;6[3]:165-6).
Lung function remains the best available biomarker for life expectancy in both patients with COPD and the general population,” wrote Dr. Soriano, a respiratory medicine researcher based in Madrid, Spain.
Additional important outcomes
Dr. Ouellette noted that while mortality is an important outcome for COPD patients, it’s not the only outcome of interest. “In addition to [trying to] help people live longer, which is certainly a desirable goal, we also want to make people be able to be more functional during their life, have fewer hospitalizations, and have less of a need of other types of supportive medical care for worsening of their disease,” he said. “The fact that the current guidelines don’t improve mortality more than the previous ones may not be a negative thing. It may tell us that the previous guidelines already did a pretty good job of helping us to improve mortality.”
Dr. Ouellette was quick to add that none of inhaled drugs currently available to treat COPD have been conclusively shown to improve mortality. “The only things we know that improve mortality for COPD patients are quitting smoking and using oxygen if a patient meets predefined goals for oxygen,” he said. “So the fact that GOLD criteria doesn’t improve mortality shouldn’t make us think that it’s not a useful tool. We already know that the medicines may not help people live longer.”
Dr. Han pointed out that spirometry “is still used to further clarify the choice of therapy recommended based on the nature and degree of airflow obstruction in light of severity of patient symptoms. The data are still designed to be used in conjunction to personalize therapy for patients.”
She added that the GOLD Science Committee “welcomes additional data analyses so that future recommendations can be further refined.”
Dr. Han disclosed that she has consulted for Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline. She has also received in-kind research support from Novartis and Sunovion.
Dr. Iftikhar reported having no financial disclosures. Dr. Ouellette is a member of CHEST® Physician’s editorial advisory board. He disclosed being part of a federally funded study being carried out by the Patient-Centered Outcomes Research Institute.
There was no industry involvement in the GOLD 2017 report, but many of its authors and board members had pharmaceutical company ties, and GOLD’s treatment advice relies on data from industry-sponsored studies.
After the Global Initiative for Chronic Obstructive Lung Disease released updated recommendations for grading COPD patients’ level of disease in November of 2016, Imran Iftikhar, MD, tried to incorporate them into his practice, but he encountered problems.
For one thing, the new classification system, which became known as GOLD 2017, uncoupled spirometry results from the ABCD treatment algorithm. “I found it wasn’t really helping me in terms of prognostication or COPD management,” said Dr. Iftikhar, section chief of pulmonary and critical care at Emory Saint Joseph’s Hospital, Atlanta. “Although the purpose of the GOLD classification was not really meant for prognostication, most practicing physicians are frequently asked about prognosis by patients, and I am not sure if the 2017 reclassification really helps with that.”
The GOLD 2017 classification simplified the chronic obstructive pulmonary disease staging that was available from 2011 to 2015 from three variables (spirometry thresholds, exacerbation risk, and dyspnea scale) to two variables (exacerbation risk and dyspnea scale). In the 2017 report, authors of the new guidelines characterized forced expiratory volume in 1 second (FEV1) as “a poor predictor of disease status” and proposed that clinicians derive ABCD groups exclusively from patient symptoms and their exacerbations. FEV1 is an “important parameter at the population level” in predicting hospitalization and mortality, the authors wrote, but keeping results separate “acknowledges the limitations of FEV1 in making treatment decisions for individualized patient care and highlights the importance of patient symptoms and exacerbation risks in guiding therapies in COPD.”
According to Meilan Han, MD, MS, a member of the GOLD Science Committee, since release of the 2017 guidelines, “clinicians have indicated that they like the flexibility the system provides in separating spirometry, symptoms, and exacerbation risk as this more accurately reflects the heterogeneity we see in the COPD patient population.” Nevertheless, how this approach influences long-term outcomes remains unclear.
Daniel Ouellette, MD, FCCP, a pulmonologist with the Henry Ford Health System in Detroit, described the GOLD 2017 criteria as “a good step forward” but said he wasn’t sure if the optimal or perfect tool exists for categorizing COPD patients’ level of disease.
“I think what we see is an effort to use all of these criteria to help us better treat our patients. I think ,” he said in an interview.
“All guidelines need to be modified as further research becomes available. I think that the frontiers of this area are going to be to incorporate new elements such as tobacco history, more emphasis on clinical signs and symptoms, and use of markers other than spirometry, such as eosinophil count, to categorize patients with COPD,” Dr. Ouellette added.
In an analysis of the GOLD 2017 criteria applied to 819 COPD patients in Spain and the United States, published online Nov. 3, 2017, in the American Journal of Respiratory and Critical Care Medicine, Carlos Cabrera López, MD, and his colleagues concluded that the mortality risk was better predicted by the 2015 GOLD classification system than by the 2017 iteration (Am J Respir Crit Care Med. 2018 Feb. doi: 10.101164/rccm.201707-1363OC).
The distribution of Charlson index scores also changed. Whereas group D was higher than B in 2015, they became similar in the 2017 system. For her part, Dr. Han emphasized that the primary goal of the GOLD ABCD classification system is to categorize patients with respect to treatment groups. “Current therapy targets symptoms and exacerbations, which are the key current elements of the classification schema,” she said in an interview. “The results of the Cabrera Lopez analysis are not necessarily unexpected, as FEV1 is associated with mortality.”
In a prospective, multicenter analysis, Portuguese researchers compared the performance of GOLD 2011 and 2017 in terms of how 200 COPD patients were reclassified, the level of agreement between the two iterations, and the performance of each to predict future exacerbations (COPD. 2018 Feb;15[1]; 21-6). They found that about half of patients classified as GOLD D under the 2011 guidelines became classified as GOLD B when the 2017 version was used, and the extent of agreement between the two iterations was moderate (P less than .001). They also found that the two versions of the guidelines were equivalently effective at predicting exacerbations (69.7% vs. 67.6% in the 2011 and 2017 iterations, respectively). In addition, patients who met the criteria for a GOLD B grouping in the 2017 iteration exacerbated 17% more often and had a lower percent predicted post bronchodilator FEV1 than did those who met the criteria for a GOLD B classification under the 2011 guidelines.
Dr. Han, who is also an associate professor of medicine at the University of Michigan Hospital, acknowledged that GOLD 2017 has resulted in the reclassification of some previously group D patients as group B patients. “Our primary goal is to aid clinicians with the diagnosis and management of patients with COPD,” she said. “We look forward to additional data coming in from ongoing clinical trials that will provide longer term data to further refine treatment algorithms.”
In a recent study of more than 33,000 Danish patients older than age 30 with COPD, researchers led by Anne Gedebjerg, MD, found that the GOLD 2017 ABCD classification did not predict all-cause and respiratory mortality more accurately than previous GOLD iterations from 2007 and 2011. Area under the curve for all-cause mortality was 0.61 for GOLD 2007, 0.61 for GOLD 2011, and 0.63 for GOLD 2017, while the area under the curve for respiratory mortality was 0.64 for GOLD 2007, 0.63 for GOLD 2011, and 0.65 for GOLD 2017 (Lancet Respir Med. 2018 Jan;6[3]:204-12).
However, when the spirometric stages 1-4 were combined with the A to D groupings based on symptoms and exacerbations, the 2017 classification predicted mortality with greater accuracy, compared with previous iterations (P less than .0001). “My practice is very much like this paper,” Dr. Iftikhar said. “I use both the spirometric grade and the ABCD grouping to specify which ‘group’ and ‘grade’ my patient belongs to. I think future investigators need to combine ABCD with spirometry classification to see how we can improve the classification system.”
In a commentary published in the same issue of the Lancet Respiratory Medicine as the large Danish study, Joan B. Soriano, MD, PhD, wrote that the 2011 GOLD guideline’s collapse of four spirometric thresholds (greater than 80%, 50%-80%, 30%-50%, and less than 30%) into just two (greater than 50% or 50% or less) “reduced the system’s ability to inform and predict mortality from the short term up to 10 years” (Lancet Respir Med. 2018 Jan;6[3]:165-6).
Lung function remains the best available biomarker for life expectancy in both patients with COPD and the general population,” wrote Dr. Soriano, a respiratory medicine researcher based in Madrid, Spain.
Additional important outcomes
Dr. Ouellette noted that while mortality is an important outcome for COPD patients, it’s not the only outcome of interest. “In addition to [trying to] help people live longer, which is certainly a desirable goal, we also want to make people be able to be more functional during their life, have fewer hospitalizations, and have less of a need of other types of supportive medical care for worsening of their disease,” he said. “The fact that the current guidelines don’t improve mortality more than the previous ones may not be a negative thing. It may tell us that the previous guidelines already did a pretty good job of helping us to improve mortality.”
Dr. Ouellette was quick to add that none of inhaled drugs currently available to treat COPD have been conclusively shown to improve mortality. “The only things we know that improve mortality for COPD patients are quitting smoking and using oxygen if a patient meets predefined goals for oxygen,” he said. “So the fact that GOLD criteria doesn’t improve mortality shouldn’t make us think that it’s not a useful tool. We already know that the medicines may not help people live longer.”
Dr. Han pointed out that spirometry “is still used to further clarify the choice of therapy recommended based on the nature and degree of airflow obstruction in light of severity of patient symptoms. The data are still designed to be used in conjunction to personalize therapy for patients.”
She added that the GOLD Science Committee “welcomes additional data analyses so that future recommendations can be further refined.”
Dr. Han disclosed that she has consulted for Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline. She has also received in-kind research support from Novartis and Sunovion.
Dr. Iftikhar reported having no financial disclosures. Dr. Ouellette is a member of CHEST® Physician’s editorial advisory board. He disclosed being part of a federally funded study being carried out by the Patient-Centered Outcomes Research Institute.
There was no industry involvement in the GOLD 2017 report, but many of its authors and board members had pharmaceutical company ties, and GOLD’s treatment advice relies on data from industry-sponsored studies.