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Is Osimertinib Better Alone or With Chemotherapy in Non–Small Cell Lung Cancer?
SAN DIEGO —
That is a question brewing among some oncologists now that the US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso, AstraZeneca) for both indications in patients with epidermal growth factor receptor (EGFR) mutations.
An answer began to emerge in research presented at the American Association for Cancer Research annual meeting.
An exploratory analysis of the FLAURA2 trial found that, when patients have EGFR mutations on baseline circulating tumor DNA (ctDNA) testing, the combination treatment can extend progression-free survival (PFS). In this patient group, those receiving osimertinib alongside pemetrexed plus cisplatin or carboplatin had a 9-month PFS advantage compared with those who received osimertinib alone.
Conversely, when patients do not have EGFR mutations following baseline ctDNA testing, osimertinib alone appears to offer similar PFS outcomes to the combination therapy, but with less toxicity.
“Baseline detection of plasma EGFR mutations may identify a subgroup of patients who derive most benefit from the addition of platinum-pemetrexed to osimertinib as first-line treatment of EGFR-mutated advance non–small cell lung cancer,” investigator Pasi A. Jänne, MD, PhD, a lung cancer oncologist at the Dana-Farber Cancer Institute, Boston, said during his presentation.
The FLAURA2 trial randomized 557 patients equally to daily osimertinib either alone or with pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by pemetrexed every 3 weeks until disease progression or unacceptable toxicity.
Patients were tested for Ex19del or L858R EGFR mutations at baseline and at 3 and 6 weeks; baseline mutations were found in 73% of evaluable patients.
In patients with baseline mutations, the median PFS was 24.8 months with the combination therapy vs 13.9 months with osimertinib alone (hazard ratio [HR], 0.60).
In patients without baseline mutations, the median PFS was similar in both groups — 33.3 months with the combination vs 30.3 months with monotherapy (HR, 0.93; 95% CI, 0.51-1.72).
The investigators also found that having baseline mutations was associated with worse outcomes regardless of study arm, and mutation clearance was associated with improved outcomes. Clearance occurred more quickly among patients receiving the combination treatment, but almost 90% of patients in both arms cleared their mutations by week 6.
“As we move forward and think about which of our patients we would treat with the combination ... the presence of baseline EGFR mutations in ctDNA may be one of the features that goes into the conversation,” Dr. Jänne said.
Study discussant Marina Chiara Garassino, MD, a thoracic oncologist at the University of Chicago, agreed that this trial can help oncologists make this kind of treatment decision.
Patients with baseline EGFR mutations also tended to have larger tumors, more brain metastases, and worse performance scores; the combination therapy makes sense when such factors are present in patients with baseline EGFR mutations, Dr. Garassino said.
The wrinkle in the findings is that the study used digital droplet polymerase chain reaction (Biodesix) to test for EGFR mutations, which is not commonly used. Clinicians often use next-generation sequencing, which is less sensitive and can lead to false negatives.
It makes it difficult to know how to apply the findings to everyday practice, but Janne hopes a study will be done to correlate next-generation sequencing detection with outcomes.
The study was funded by AstraZeneca, maker of osimertinib, and researchers included AstraZeneca employees. Dr. Jänne is a consultant for and reported research funding from the company. He is a co-inventor on an EGFR mutations patent. Dr. Garassino is also an AstraZeneca consultant and reported institutional financial interests in the company.
A version of this article appeared on Medscape.com.
SAN DIEGO —
That is a question brewing among some oncologists now that the US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso, AstraZeneca) for both indications in patients with epidermal growth factor receptor (EGFR) mutations.
An answer began to emerge in research presented at the American Association for Cancer Research annual meeting.
An exploratory analysis of the FLAURA2 trial found that, when patients have EGFR mutations on baseline circulating tumor DNA (ctDNA) testing, the combination treatment can extend progression-free survival (PFS). In this patient group, those receiving osimertinib alongside pemetrexed plus cisplatin or carboplatin had a 9-month PFS advantage compared with those who received osimertinib alone.
Conversely, when patients do not have EGFR mutations following baseline ctDNA testing, osimertinib alone appears to offer similar PFS outcomes to the combination therapy, but with less toxicity.
“Baseline detection of plasma EGFR mutations may identify a subgroup of patients who derive most benefit from the addition of platinum-pemetrexed to osimertinib as first-line treatment of EGFR-mutated advance non–small cell lung cancer,” investigator Pasi A. Jänne, MD, PhD, a lung cancer oncologist at the Dana-Farber Cancer Institute, Boston, said during his presentation.
The FLAURA2 trial randomized 557 patients equally to daily osimertinib either alone or with pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by pemetrexed every 3 weeks until disease progression or unacceptable toxicity.
Patients were tested for Ex19del or L858R EGFR mutations at baseline and at 3 and 6 weeks; baseline mutations were found in 73% of evaluable patients.
In patients with baseline mutations, the median PFS was 24.8 months with the combination therapy vs 13.9 months with osimertinib alone (hazard ratio [HR], 0.60).
In patients without baseline mutations, the median PFS was similar in both groups — 33.3 months with the combination vs 30.3 months with monotherapy (HR, 0.93; 95% CI, 0.51-1.72).
The investigators also found that having baseline mutations was associated with worse outcomes regardless of study arm, and mutation clearance was associated with improved outcomes. Clearance occurred more quickly among patients receiving the combination treatment, but almost 90% of patients in both arms cleared their mutations by week 6.
“As we move forward and think about which of our patients we would treat with the combination ... the presence of baseline EGFR mutations in ctDNA may be one of the features that goes into the conversation,” Dr. Jänne said.
Study discussant Marina Chiara Garassino, MD, a thoracic oncologist at the University of Chicago, agreed that this trial can help oncologists make this kind of treatment decision.
Patients with baseline EGFR mutations also tended to have larger tumors, more brain metastases, and worse performance scores; the combination therapy makes sense when such factors are present in patients with baseline EGFR mutations, Dr. Garassino said.
The wrinkle in the findings is that the study used digital droplet polymerase chain reaction (Biodesix) to test for EGFR mutations, which is not commonly used. Clinicians often use next-generation sequencing, which is less sensitive and can lead to false negatives.
It makes it difficult to know how to apply the findings to everyday practice, but Janne hopes a study will be done to correlate next-generation sequencing detection with outcomes.
The study was funded by AstraZeneca, maker of osimertinib, and researchers included AstraZeneca employees. Dr. Jänne is a consultant for and reported research funding from the company. He is a co-inventor on an EGFR mutations patent. Dr. Garassino is also an AstraZeneca consultant and reported institutional financial interests in the company.
A version of this article appeared on Medscape.com.
SAN DIEGO —
That is a question brewing among some oncologists now that the US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso, AstraZeneca) for both indications in patients with epidermal growth factor receptor (EGFR) mutations.
An answer began to emerge in research presented at the American Association for Cancer Research annual meeting.
An exploratory analysis of the FLAURA2 trial found that, when patients have EGFR mutations on baseline circulating tumor DNA (ctDNA) testing, the combination treatment can extend progression-free survival (PFS). In this patient group, those receiving osimertinib alongside pemetrexed plus cisplatin or carboplatin had a 9-month PFS advantage compared with those who received osimertinib alone.
Conversely, when patients do not have EGFR mutations following baseline ctDNA testing, osimertinib alone appears to offer similar PFS outcomes to the combination therapy, but with less toxicity.
“Baseline detection of plasma EGFR mutations may identify a subgroup of patients who derive most benefit from the addition of platinum-pemetrexed to osimertinib as first-line treatment of EGFR-mutated advance non–small cell lung cancer,” investigator Pasi A. Jänne, MD, PhD, a lung cancer oncologist at the Dana-Farber Cancer Institute, Boston, said during his presentation.
The FLAURA2 trial randomized 557 patients equally to daily osimertinib either alone or with pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by pemetrexed every 3 weeks until disease progression or unacceptable toxicity.
Patients were tested for Ex19del or L858R EGFR mutations at baseline and at 3 and 6 weeks; baseline mutations were found in 73% of evaluable patients.
In patients with baseline mutations, the median PFS was 24.8 months with the combination therapy vs 13.9 months with osimertinib alone (hazard ratio [HR], 0.60).
In patients without baseline mutations, the median PFS was similar in both groups — 33.3 months with the combination vs 30.3 months with monotherapy (HR, 0.93; 95% CI, 0.51-1.72).
The investigators also found that having baseline mutations was associated with worse outcomes regardless of study arm, and mutation clearance was associated with improved outcomes. Clearance occurred more quickly among patients receiving the combination treatment, but almost 90% of patients in both arms cleared their mutations by week 6.
“As we move forward and think about which of our patients we would treat with the combination ... the presence of baseline EGFR mutations in ctDNA may be one of the features that goes into the conversation,” Dr. Jänne said.
Study discussant Marina Chiara Garassino, MD, a thoracic oncologist at the University of Chicago, agreed that this trial can help oncologists make this kind of treatment decision.
Patients with baseline EGFR mutations also tended to have larger tumors, more brain metastases, and worse performance scores; the combination therapy makes sense when such factors are present in patients with baseline EGFR mutations, Dr. Garassino said.
The wrinkle in the findings is that the study used digital droplet polymerase chain reaction (Biodesix) to test for EGFR mutations, which is not commonly used. Clinicians often use next-generation sequencing, which is less sensitive and can lead to false negatives.
It makes it difficult to know how to apply the findings to everyday practice, but Janne hopes a study will be done to correlate next-generation sequencing detection with outcomes.
The study was funded by AstraZeneca, maker of osimertinib, and researchers included AstraZeneca employees. Dr. Jänne is a consultant for and reported research funding from the company. He is a co-inventor on an EGFR mutations patent. Dr. Garassino is also an AstraZeneca consultant and reported institutional financial interests in the company.
A version of this article appeared on Medscape.com.
FROM AACR
Inflammation Affects Association Between Furan Exposure and Chronic Obstructive Pulmonary Disease
TOPLINE:
Exposure to furan, a chemical present in agricultural products, stabilizers, pharmaceuticals, and heat-processed foods, shows a significant positive correlation with the prevalence and respiratory mortality of chronic obstructive pulmonary disease (COPD).
METHODOLOGY:
- The researchers reviewed data from the National Health and Nutrition Examination Survey database from 2013 to 2018 and identified 270 adults with a diagnosis of COPD and 7212 without.
- The researchers used a restricted cubic spline analysis to examine the association between COPD risk and blood furan levels and mediating analysis to explore the impact of inflammation.
- The primary outcome of the study was respiratory mortality.
TAKEAWAY:
- Ten COPD patients died of respiratory diseases; adjusted analysis showed a positive correlation between log10-transformed blood furan levels and respiratory mortality in COPD patients (hazard ratio, 41.00, P = .003).
- In a logistic regression analysis, log10-transformed blood furan levels were significantly associated with increased risk for COPD; individuals in the fifth quartile had significantly increased risk compared with the first quartile (odds ratio, 4.47; P = .006).
- COPD demonstrated a significant positive association with monocytes, neutrophils, and basophils, which showed mediated proportions of 8.73%, 20.90%, and 10.94%, respectively, in the relationship between furan exposure and prevalence of COPD (P < .05 for all).
IN PRACTICE:
“The implication [of the findings] is that reducing exposure to furan in the environment could potentially lower the incidence of COPD and improve the prognosis for COPD patients,” but large-scale prospective cohort studies are needed, the researchers wrote in their conclusion.
SOURCE:
The lead author of the study was Di Sun, MD, of Capital Medical University, Beijing, China. The study was published online in BMC Public Health.
LIMITATIONS:
The cross-sectional design prevented establishment of a causal relationship between furan exposure and COPD; lack of data on the conditions of furan exposure and the reliance on self-reports for COPD diagnosis were among the factors that limited the study findings.
DISCLOSURES:
The study was supported by the High Level Public Health Technology Talent Construction Project and Reform and Development Program of Beijing Institute of Respiratory Medicine. The researchers had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
TOPLINE:
Exposure to furan, a chemical present in agricultural products, stabilizers, pharmaceuticals, and heat-processed foods, shows a significant positive correlation with the prevalence and respiratory mortality of chronic obstructive pulmonary disease (COPD).
METHODOLOGY:
- The researchers reviewed data from the National Health and Nutrition Examination Survey database from 2013 to 2018 and identified 270 adults with a diagnosis of COPD and 7212 without.
- The researchers used a restricted cubic spline analysis to examine the association between COPD risk and blood furan levels and mediating analysis to explore the impact of inflammation.
- The primary outcome of the study was respiratory mortality.
TAKEAWAY:
- Ten COPD patients died of respiratory diseases; adjusted analysis showed a positive correlation between log10-transformed blood furan levels and respiratory mortality in COPD patients (hazard ratio, 41.00, P = .003).
- In a logistic regression analysis, log10-transformed blood furan levels were significantly associated with increased risk for COPD; individuals in the fifth quartile had significantly increased risk compared with the first quartile (odds ratio, 4.47; P = .006).
- COPD demonstrated a significant positive association with monocytes, neutrophils, and basophils, which showed mediated proportions of 8.73%, 20.90%, and 10.94%, respectively, in the relationship between furan exposure and prevalence of COPD (P < .05 for all).
IN PRACTICE:
“The implication [of the findings] is that reducing exposure to furan in the environment could potentially lower the incidence of COPD and improve the prognosis for COPD patients,” but large-scale prospective cohort studies are needed, the researchers wrote in their conclusion.
SOURCE:
The lead author of the study was Di Sun, MD, of Capital Medical University, Beijing, China. The study was published online in BMC Public Health.
LIMITATIONS:
The cross-sectional design prevented establishment of a causal relationship between furan exposure and COPD; lack of data on the conditions of furan exposure and the reliance on self-reports for COPD diagnosis were among the factors that limited the study findings.
DISCLOSURES:
The study was supported by the High Level Public Health Technology Talent Construction Project and Reform and Development Program of Beijing Institute of Respiratory Medicine. The researchers had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
TOPLINE:
Exposure to furan, a chemical present in agricultural products, stabilizers, pharmaceuticals, and heat-processed foods, shows a significant positive correlation with the prevalence and respiratory mortality of chronic obstructive pulmonary disease (COPD).
METHODOLOGY:
- The researchers reviewed data from the National Health and Nutrition Examination Survey database from 2013 to 2018 and identified 270 adults with a diagnosis of COPD and 7212 without.
- The researchers used a restricted cubic spline analysis to examine the association between COPD risk and blood furan levels and mediating analysis to explore the impact of inflammation.
- The primary outcome of the study was respiratory mortality.
TAKEAWAY:
- Ten COPD patients died of respiratory diseases; adjusted analysis showed a positive correlation between log10-transformed blood furan levels and respiratory mortality in COPD patients (hazard ratio, 41.00, P = .003).
- In a logistic regression analysis, log10-transformed blood furan levels were significantly associated with increased risk for COPD; individuals in the fifth quartile had significantly increased risk compared with the first quartile (odds ratio, 4.47; P = .006).
- COPD demonstrated a significant positive association with monocytes, neutrophils, and basophils, which showed mediated proportions of 8.73%, 20.90%, and 10.94%, respectively, in the relationship between furan exposure and prevalence of COPD (P < .05 for all).
IN PRACTICE:
“The implication [of the findings] is that reducing exposure to furan in the environment could potentially lower the incidence of COPD and improve the prognosis for COPD patients,” but large-scale prospective cohort studies are needed, the researchers wrote in their conclusion.
SOURCE:
The lead author of the study was Di Sun, MD, of Capital Medical University, Beijing, China. The study was published online in BMC Public Health.
LIMITATIONS:
The cross-sectional design prevented establishment of a causal relationship between furan exposure and COPD; lack of data on the conditions of furan exposure and the reliance on self-reports for COPD diagnosis were among the factors that limited the study findings.
DISCLOSURES:
The study was supported by the High Level Public Health Technology Talent Construction Project and Reform and Development Program of Beijing Institute of Respiratory Medicine. The researchers had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Drug Prototype Shows Promise for Stem Cell Treatment of Pulmonary Disease
A drug prototype known as NZ-97 showed promise for treating pulmonary disease by stimulating growth of new stem cells to repair damaged tissue, based on data from a new proof-of-concept study.
In many pulmonary diseases, insufficient stem cells allow damage to progress, but researchers have developed a lung-targeted, drug-like small molecule to stimulate the growth of lung stem cells, according to data published in Proceedings of the National Academy of Sciences.
Michael J. Bollong, PhD, associate professor in the department of chemistry at Scripps Research, San Diego, and colleagues used ReFRAME, a drug repurposing library and database created by the Calibr-Skaggs Institute for Innovative Medicines (the drug discovery arm of Scripps Research) to test existing drugs as foundations to promote stem cell growth and repair in the lungs.
“At present, there are no drugs which promote regenerative repair of the lung,” Dr. Bollong said in an interview. “This is especially important in idiopathic pulmonary fibrosis, as this disease is driven by an insufficiency of the stem cell population of the lower airway, alveolar type 2 cells (AEC2s), to proliferate and to regenerate the gas exchange epithelium,” he said.
The researchers identified dipeptidyl peptidase 4 (DPP4) inhibitors as potential tools to help promote production of stem cells in the lower airway called AEC2s. Dysfunction of AEC2 is thought to play a key role in the pathogenesis of idiopathic pulmonary fibrosis, the researchers noted in the study. They created a new and highly soluble DPP4 inhibitor known as NZ-97 that could be administered via intratracheal injection.
In addition, 1 month of treatment with 0.5 mg/kg of NZ-97 every fourth day showed no detectable changes in alveolar structure, increased inflammation, or cellular hyperplasia.
The current research “identifies a novel mechanism for promoting alveolar repair” and treating not only idiopathic pulmonary fibrosis (IPF) but potentially other pulmonary diseases, such as chronic obstructive pulmonary disease, Dr. Bollong said.
“Here we reported a drug prototype, NZ-97, a locally delivered and lung-retained molecule that inhibits DPP4 in the lumen of the lung,” Bollong explained. The NZ-97 prototype drug is chemically similar to CMR316, a new clinical drug candidate from researchers at Calibr-Skaggs that is scheduled to start a phase 1 clinical trial later in the summer of 2024, according to Dr. Bollong.
CMR316 is designed to be delivered once a week in mist form via a nebulizer. “If CMR316 demonstrates ameliorative efficacy in IPF, it could provide a novel avenue for regenerating the lung and could be added on top of standard-of-care anti-fibrotic drugs to delay or potentially even reverse disease progression,” Dr. Bollong told this news organization.
“The key challenge will be understanding if the identified regenerative mechanism will show ameliorative efficacy in a clinical trial,” Dr. Bollong said. “While we have shown effects in animal models and patient-derived cells, the degree and duration of the ameliorative effect in patients will ultimately be determined in the clinic.”
Looking ahead, the CMR316 phase 1 clinical trial is designed to evaluate safety and target engagement, Dr. Bollong said. Dr. Bollong’s lab continues to collaborate with Calibr to develop other regenerative approaches to the treatment of disease in other organs, he said.
Meeting the Need for Regenerative Treatment
The current study and the ongoing research into NZ-97 address the need for regenerative therapies in pulmonary disease, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, Texas, said in an interview.
“Identifying DPP4 inhibitors, particularly NZ-97, as potential agents for expanding type 2 alveolar epithelial cells (AEC2s) represents a promising therapeutic strategy to stimulate the regeneration of damaged alveolar epithelium,” she said. “The AEC2s play a crucial role in lung repair, and targeting these could potentially ameliorate various lung diseases that currently lack effective treatments,” she explained.
“DPP4 inhibitors are well-established in diabetes management and have known biological actions; however, the successful repurposing and effectiveness of NZ-97 in promoting lung repair are surprising to some extent,” said Dr. Narendra. “This surprise stems from this medication’s novel application and efficacy in a pulmonary context, showing significant potential where traditional DPP4 inhibitors required higher, potentially unsafe doses to achieve similar effects,” she said.
Should research prove successful, NZ-97 could offer substantial clinical benefits for treating pulmonary diseases such as IPF and other conditions involving alveolar damage. By enhancing AEC2 proliferation, NZ-97 may improve patient outcomes by mitigating lung damage and promoting regenerative repair, possibly reducing the dependency on more invasive treatments like lung transplantation.
More research on NZ-97 is needed in order to identify potential barriers to its use, Dr. Narendra said. “Further studies are needed to evaluate the long-term effects of NZ-97, understand its mechanisms in human lung tissue, and determine its safety and efficacy in clinical settings.”
Dr. Narendra had no financial conflicts to disclose but served on the Editorial Board of Chest Physician.
A version of this article appeared on Medscape.com.
A drug prototype known as NZ-97 showed promise for treating pulmonary disease by stimulating growth of new stem cells to repair damaged tissue, based on data from a new proof-of-concept study.
In many pulmonary diseases, insufficient stem cells allow damage to progress, but researchers have developed a lung-targeted, drug-like small molecule to stimulate the growth of lung stem cells, according to data published in Proceedings of the National Academy of Sciences.
Michael J. Bollong, PhD, associate professor in the department of chemistry at Scripps Research, San Diego, and colleagues used ReFRAME, a drug repurposing library and database created by the Calibr-Skaggs Institute for Innovative Medicines (the drug discovery arm of Scripps Research) to test existing drugs as foundations to promote stem cell growth and repair in the lungs.
“At present, there are no drugs which promote regenerative repair of the lung,” Dr. Bollong said in an interview. “This is especially important in idiopathic pulmonary fibrosis, as this disease is driven by an insufficiency of the stem cell population of the lower airway, alveolar type 2 cells (AEC2s), to proliferate and to regenerate the gas exchange epithelium,” he said.
The researchers identified dipeptidyl peptidase 4 (DPP4) inhibitors as potential tools to help promote production of stem cells in the lower airway called AEC2s. Dysfunction of AEC2 is thought to play a key role in the pathogenesis of idiopathic pulmonary fibrosis, the researchers noted in the study. They created a new and highly soluble DPP4 inhibitor known as NZ-97 that could be administered via intratracheal injection.
In addition, 1 month of treatment with 0.5 mg/kg of NZ-97 every fourth day showed no detectable changes in alveolar structure, increased inflammation, or cellular hyperplasia.
The current research “identifies a novel mechanism for promoting alveolar repair” and treating not only idiopathic pulmonary fibrosis (IPF) but potentially other pulmonary diseases, such as chronic obstructive pulmonary disease, Dr. Bollong said.
“Here we reported a drug prototype, NZ-97, a locally delivered and lung-retained molecule that inhibits DPP4 in the lumen of the lung,” Bollong explained. The NZ-97 prototype drug is chemically similar to CMR316, a new clinical drug candidate from researchers at Calibr-Skaggs that is scheduled to start a phase 1 clinical trial later in the summer of 2024, according to Dr. Bollong.
CMR316 is designed to be delivered once a week in mist form via a nebulizer. “If CMR316 demonstrates ameliorative efficacy in IPF, it could provide a novel avenue for regenerating the lung and could be added on top of standard-of-care anti-fibrotic drugs to delay or potentially even reverse disease progression,” Dr. Bollong told this news organization.
“The key challenge will be understanding if the identified regenerative mechanism will show ameliorative efficacy in a clinical trial,” Dr. Bollong said. “While we have shown effects in animal models and patient-derived cells, the degree and duration of the ameliorative effect in patients will ultimately be determined in the clinic.”
Looking ahead, the CMR316 phase 1 clinical trial is designed to evaluate safety and target engagement, Dr. Bollong said. Dr. Bollong’s lab continues to collaborate with Calibr to develop other regenerative approaches to the treatment of disease in other organs, he said.
Meeting the Need for Regenerative Treatment
The current study and the ongoing research into NZ-97 address the need for regenerative therapies in pulmonary disease, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, Texas, said in an interview.
“Identifying DPP4 inhibitors, particularly NZ-97, as potential agents for expanding type 2 alveolar epithelial cells (AEC2s) represents a promising therapeutic strategy to stimulate the regeneration of damaged alveolar epithelium,” she said. “The AEC2s play a crucial role in lung repair, and targeting these could potentially ameliorate various lung diseases that currently lack effective treatments,” she explained.
“DPP4 inhibitors are well-established in diabetes management and have known biological actions; however, the successful repurposing and effectiveness of NZ-97 in promoting lung repair are surprising to some extent,” said Dr. Narendra. “This surprise stems from this medication’s novel application and efficacy in a pulmonary context, showing significant potential where traditional DPP4 inhibitors required higher, potentially unsafe doses to achieve similar effects,” she said.
Should research prove successful, NZ-97 could offer substantial clinical benefits for treating pulmonary diseases such as IPF and other conditions involving alveolar damage. By enhancing AEC2 proliferation, NZ-97 may improve patient outcomes by mitigating lung damage and promoting regenerative repair, possibly reducing the dependency on more invasive treatments like lung transplantation.
More research on NZ-97 is needed in order to identify potential barriers to its use, Dr. Narendra said. “Further studies are needed to evaluate the long-term effects of NZ-97, understand its mechanisms in human lung tissue, and determine its safety and efficacy in clinical settings.”
Dr. Narendra had no financial conflicts to disclose but served on the Editorial Board of Chest Physician.
A version of this article appeared on Medscape.com.
A drug prototype known as NZ-97 showed promise for treating pulmonary disease by stimulating growth of new stem cells to repair damaged tissue, based on data from a new proof-of-concept study.
In many pulmonary diseases, insufficient stem cells allow damage to progress, but researchers have developed a lung-targeted, drug-like small molecule to stimulate the growth of lung stem cells, according to data published in Proceedings of the National Academy of Sciences.
Michael J. Bollong, PhD, associate professor in the department of chemistry at Scripps Research, San Diego, and colleagues used ReFRAME, a drug repurposing library and database created by the Calibr-Skaggs Institute for Innovative Medicines (the drug discovery arm of Scripps Research) to test existing drugs as foundations to promote stem cell growth and repair in the lungs.
“At present, there are no drugs which promote regenerative repair of the lung,” Dr. Bollong said in an interview. “This is especially important in idiopathic pulmonary fibrosis, as this disease is driven by an insufficiency of the stem cell population of the lower airway, alveolar type 2 cells (AEC2s), to proliferate and to regenerate the gas exchange epithelium,” he said.
The researchers identified dipeptidyl peptidase 4 (DPP4) inhibitors as potential tools to help promote production of stem cells in the lower airway called AEC2s. Dysfunction of AEC2 is thought to play a key role in the pathogenesis of idiopathic pulmonary fibrosis, the researchers noted in the study. They created a new and highly soluble DPP4 inhibitor known as NZ-97 that could be administered via intratracheal injection.
In addition, 1 month of treatment with 0.5 mg/kg of NZ-97 every fourth day showed no detectable changes in alveolar structure, increased inflammation, or cellular hyperplasia.
The current research “identifies a novel mechanism for promoting alveolar repair” and treating not only idiopathic pulmonary fibrosis (IPF) but potentially other pulmonary diseases, such as chronic obstructive pulmonary disease, Dr. Bollong said.
“Here we reported a drug prototype, NZ-97, a locally delivered and lung-retained molecule that inhibits DPP4 in the lumen of the lung,” Bollong explained. The NZ-97 prototype drug is chemically similar to CMR316, a new clinical drug candidate from researchers at Calibr-Skaggs that is scheduled to start a phase 1 clinical trial later in the summer of 2024, according to Dr. Bollong.
CMR316 is designed to be delivered once a week in mist form via a nebulizer. “If CMR316 demonstrates ameliorative efficacy in IPF, it could provide a novel avenue for regenerating the lung and could be added on top of standard-of-care anti-fibrotic drugs to delay or potentially even reverse disease progression,” Dr. Bollong told this news organization.
“The key challenge will be understanding if the identified regenerative mechanism will show ameliorative efficacy in a clinical trial,” Dr. Bollong said. “While we have shown effects in animal models and patient-derived cells, the degree and duration of the ameliorative effect in patients will ultimately be determined in the clinic.”
Looking ahead, the CMR316 phase 1 clinical trial is designed to evaluate safety and target engagement, Dr. Bollong said. Dr. Bollong’s lab continues to collaborate with Calibr to develop other regenerative approaches to the treatment of disease in other organs, he said.
Meeting the Need for Regenerative Treatment
The current study and the ongoing research into NZ-97 address the need for regenerative therapies in pulmonary disease, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, Texas, said in an interview.
“Identifying DPP4 inhibitors, particularly NZ-97, as potential agents for expanding type 2 alveolar epithelial cells (AEC2s) represents a promising therapeutic strategy to stimulate the regeneration of damaged alveolar epithelium,” she said. “The AEC2s play a crucial role in lung repair, and targeting these could potentially ameliorate various lung diseases that currently lack effective treatments,” she explained.
“DPP4 inhibitors are well-established in diabetes management and have known biological actions; however, the successful repurposing and effectiveness of NZ-97 in promoting lung repair are surprising to some extent,” said Dr. Narendra. “This surprise stems from this medication’s novel application and efficacy in a pulmonary context, showing significant potential where traditional DPP4 inhibitors required higher, potentially unsafe doses to achieve similar effects,” she said.
Should research prove successful, NZ-97 could offer substantial clinical benefits for treating pulmonary diseases such as IPF and other conditions involving alveolar damage. By enhancing AEC2 proliferation, NZ-97 may improve patient outcomes by mitigating lung damage and promoting regenerative repair, possibly reducing the dependency on more invasive treatments like lung transplantation.
More research on NZ-97 is needed in order to identify potential barriers to its use, Dr. Narendra said. “Further studies are needed to evaluate the long-term effects of NZ-97, understand its mechanisms in human lung tissue, and determine its safety and efficacy in clinical settings.”
Dr. Narendra had no financial conflicts to disclose but served on the Editorial Board of Chest Physician.
A version of this article appeared on Medscape.com.
Time to Lung Disease in Patients With Dermatomyositis Subtype Estimated
TOPLINE:
The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.
METHODOLOGY:
- , with the former having a particularly high mortality rate.
- In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
- The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.
TAKEAWAY:
- Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
- ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
- The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
- Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.
IN PRACTICE:
“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.
SOURCE:
This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.
LIMITATIONS:
Study limitations were the study’s retrospective design and small sample size.
DISCLOSURES:
No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.
METHODOLOGY:
- , with the former having a particularly high mortality rate.
- In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
- The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.
TAKEAWAY:
- Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
- ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
- The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
- Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.
IN PRACTICE:
“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.
SOURCE:
This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.
LIMITATIONS:
Study limitations were the study’s retrospective design and small sample size.
DISCLOSURES:
No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.
METHODOLOGY:
- , with the former having a particularly high mortality rate.
- In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
- The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.
TAKEAWAY:
- Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
- ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
- The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
- Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.
IN PRACTICE:
“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.
SOURCE:
This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.
LIMITATIONS:
Study limitations were the study’s retrospective design and small sample size.
DISCLOSURES:
No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.
A version of this article appeared on Medscape.com.
Why Lung Cancer Screening Is Not for Everyone
Why does this happen? Could it also occur in Italy?
Reasons in Favor
The authors of the study, which was published in Annals of Family Medicine interviewed 40 former military personnel with a significant history of smoking. Though the patients presented with various comorbidities and had a limited life expectancy, the Veterans Health Administration had offered them lung cancer screening.
Of the 40 respondents, 26 had accepted the screening test. When asked why they had done so, they responded, “to take care of my health and achieve my life goals,” “because screening is an opportunity to identify potential issues,” “because it was recommended by a doctor I trust,” and “because I don’t want to regret not accepting it.” Strangely, when deciding about lung cancer screening, the respondents did not consider their poor health or life expectancy.
Potential Harms
The screening was also welcomed because low-dose computed tomography (LDCT) is a noninvasive test. However, many participants were unaware that the screening needed to be repeated annually and that further imaging or other types of tests could follow LDCT, such as biopsies and bronchoscopies.
Many did not recall discussing with the doctor the potential harms of screening, including overdiagnosis, stress due to false positives, and complications and risks associated with investigations and treatments. Informed about this, several patients stated that they would not necessarily undergo further tests or antitumor treatments, especially if intensive or invasive.
The authors of the article emphasized the importance of shared decision-making with patients who have a marginal expected benefit from screening. But is it correct to offer screening under these conditions? Guidelines advise against screening individuals with limited life expectancy and multiple comorbidities because the risk-benefit ratio is not favorable.
Screening in Italy
Italy has no organized public program for lung screening. However, in 2022, the Rete Italiana Screening Polmonare (RISP) program for early lung cancer diagnosis was launched. Supported by European funds, it is coordinated by the National Cancer Institute (INT) in Milan and aims to recruit 10,000 high-risk candidates for free screening at 18 hospitals across Italy.
Optimizing participant selection is important in any screening, but in a program like RISP, it is essential, said Alessandro Pardolesi, MD, a thoracic surgeon at INT. “Subjects with multiple comorbidities would create a limit to the study, because there would be too many confounding factors. By maintaining correct inclusion criteria, we can build a reproducible model to demonstrate that screening has a clear social and economic impact. Only after proving its effectiveness can we consider extending it to patients with pre-existing issues or who are very elderly,” he said. The RISP project is limited to participants aged 55-75 years. Participants must be smokers or have quit smoking no more than 15 years ago, with an average consumption of 20 cigarettes per day for 30 years.
Participant selection for the RISP program is also dictated by the costs to be incurred. “If something emerges from the CT scan, whether oncologic or not, it needs to be investigated, triggering mechanisms that consume time, space, and resources,” said Dr. Pardolesi. The economic aspect is crucial for determining the effectiveness of screening. “We need to demonstrate that in addition to increasing the patient’s life expectancy, healthcare costs are reduced. By anticipating the diagnosis, the intervention is less expensive, the patient is discharged in three days, and there’s no need for therapy, so there’s a saving. This is important, given the increasingly evident economic problems of the Italian public health system,” said Dr. Pardolesi.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Why does this happen? Could it also occur in Italy?
Reasons in Favor
The authors of the study, which was published in Annals of Family Medicine interviewed 40 former military personnel with a significant history of smoking. Though the patients presented with various comorbidities and had a limited life expectancy, the Veterans Health Administration had offered them lung cancer screening.
Of the 40 respondents, 26 had accepted the screening test. When asked why they had done so, they responded, “to take care of my health and achieve my life goals,” “because screening is an opportunity to identify potential issues,” “because it was recommended by a doctor I trust,” and “because I don’t want to regret not accepting it.” Strangely, when deciding about lung cancer screening, the respondents did not consider their poor health or life expectancy.
Potential Harms
The screening was also welcomed because low-dose computed tomography (LDCT) is a noninvasive test. However, many participants were unaware that the screening needed to be repeated annually and that further imaging or other types of tests could follow LDCT, such as biopsies and bronchoscopies.
Many did not recall discussing with the doctor the potential harms of screening, including overdiagnosis, stress due to false positives, and complications and risks associated with investigations and treatments. Informed about this, several patients stated that they would not necessarily undergo further tests or antitumor treatments, especially if intensive or invasive.
The authors of the article emphasized the importance of shared decision-making with patients who have a marginal expected benefit from screening. But is it correct to offer screening under these conditions? Guidelines advise against screening individuals with limited life expectancy and multiple comorbidities because the risk-benefit ratio is not favorable.
Screening in Italy
Italy has no organized public program for lung screening. However, in 2022, the Rete Italiana Screening Polmonare (RISP) program for early lung cancer diagnosis was launched. Supported by European funds, it is coordinated by the National Cancer Institute (INT) in Milan and aims to recruit 10,000 high-risk candidates for free screening at 18 hospitals across Italy.
Optimizing participant selection is important in any screening, but in a program like RISP, it is essential, said Alessandro Pardolesi, MD, a thoracic surgeon at INT. “Subjects with multiple comorbidities would create a limit to the study, because there would be too many confounding factors. By maintaining correct inclusion criteria, we can build a reproducible model to demonstrate that screening has a clear social and economic impact. Only after proving its effectiveness can we consider extending it to patients with pre-existing issues or who are very elderly,” he said. The RISP project is limited to participants aged 55-75 years. Participants must be smokers or have quit smoking no more than 15 years ago, with an average consumption of 20 cigarettes per day for 30 years.
Participant selection for the RISP program is also dictated by the costs to be incurred. “If something emerges from the CT scan, whether oncologic or not, it needs to be investigated, triggering mechanisms that consume time, space, and resources,” said Dr. Pardolesi. The economic aspect is crucial for determining the effectiveness of screening. “We need to demonstrate that in addition to increasing the patient’s life expectancy, healthcare costs are reduced. By anticipating the diagnosis, the intervention is less expensive, the patient is discharged in three days, and there’s no need for therapy, so there’s a saving. This is important, given the increasingly evident economic problems of the Italian public health system,” said Dr. Pardolesi.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Why does this happen? Could it also occur in Italy?
Reasons in Favor
The authors of the study, which was published in Annals of Family Medicine interviewed 40 former military personnel with a significant history of smoking. Though the patients presented with various comorbidities and had a limited life expectancy, the Veterans Health Administration had offered them lung cancer screening.
Of the 40 respondents, 26 had accepted the screening test. When asked why they had done so, they responded, “to take care of my health and achieve my life goals,” “because screening is an opportunity to identify potential issues,” “because it was recommended by a doctor I trust,” and “because I don’t want to regret not accepting it.” Strangely, when deciding about lung cancer screening, the respondents did not consider their poor health or life expectancy.
Potential Harms
The screening was also welcomed because low-dose computed tomography (LDCT) is a noninvasive test. However, many participants were unaware that the screening needed to be repeated annually and that further imaging or other types of tests could follow LDCT, such as biopsies and bronchoscopies.
Many did not recall discussing with the doctor the potential harms of screening, including overdiagnosis, stress due to false positives, and complications and risks associated with investigations and treatments. Informed about this, several patients stated that they would not necessarily undergo further tests or antitumor treatments, especially if intensive or invasive.
The authors of the article emphasized the importance of shared decision-making with patients who have a marginal expected benefit from screening. But is it correct to offer screening under these conditions? Guidelines advise against screening individuals with limited life expectancy and multiple comorbidities because the risk-benefit ratio is not favorable.
Screening in Italy
Italy has no organized public program for lung screening. However, in 2022, the Rete Italiana Screening Polmonare (RISP) program for early lung cancer diagnosis was launched. Supported by European funds, it is coordinated by the National Cancer Institute (INT) in Milan and aims to recruit 10,000 high-risk candidates for free screening at 18 hospitals across Italy.
Optimizing participant selection is important in any screening, but in a program like RISP, it is essential, said Alessandro Pardolesi, MD, a thoracic surgeon at INT. “Subjects with multiple comorbidities would create a limit to the study, because there would be too many confounding factors. By maintaining correct inclusion criteria, we can build a reproducible model to demonstrate that screening has a clear social and economic impact. Only after proving its effectiveness can we consider extending it to patients with pre-existing issues or who are very elderly,” he said. The RISP project is limited to participants aged 55-75 years. Participants must be smokers or have quit smoking no more than 15 years ago, with an average consumption of 20 cigarettes per day for 30 years.
Participant selection for the RISP program is also dictated by the costs to be incurred. “If something emerges from the CT scan, whether oncologic or not, it needs to be investigated, triggering mechanisms that consume time, space, and resources,” said Dr. Pardolesi. The economic aspect is crucial for determining the effectiveness of screening. “We need to demonstrate that in addition to increasing the patient’s life expectancy, healthcare costs are reduced. By anticipating the diagnosis, the intervention is less expensive, the patient is discharged in three days, and there’s no need for therapy, so there’s a saving. This is important, given the increasingly evident economic problems of the Italian public health system,” said Dr. Pardolesi.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
What Are Platanus Cough and Thunderstorm Asthma?
Because of climate change, heat waves, storms, heavy rainfalls, and floods are now occurring in areas that seldom experienced these phenomena before. “Extreme weather events are rare, but in terms of their extent, duration, and scale, they are unusual. And they are increasing due to climate change,” said Andrea Elmer, MD, an internal medicine and pulmonology specialist at the DKD Helios Clinic in Wiesbaden, Germany. She spoke at the Congress of the German Society for Pneumology and Respiratory Medicine.
Dr. Elmer referred to the 2023 status report by the Robert Koch Institute and the 2023 Synthesis Report by the Intergovernmental Panel on Climate Change, in which the likelihood of extreme weather events was acknowledged to be significantly higher than previously recognized. “Knowing about such extreme weather events is important to assess the consequences for our patients and to identify possible medical care needs,” said Dr. Elmer. She focused on the effects of platanus (plane tree) cough and thunderstorm asthma.
Platanus Cough
The symptoms worsened when the children left the building and waited in the schoolyard. Initially, a chemical attack with irritant gas was suspected because the school is located near an industrial area. There were no indications of a pollen cloud.
Eventually, doctors and firefighters found that the symptoms were caused by platanus cough, which is induced by the fine star-shaped hair found on young platanus leaves, bark, young branches, and buds. If strong winds move the leaves after prolonged dryness, these trichomes can break off when touched, creating platanus dust.
At that time, there were unusual climatic conditions. The temperature was 29 °C, it was dry, and wind gusts reached 50 km/h. The schoolyard was enclosed and densely planted with tall, old plane trees. Initial symptoms occurred in classrooms with open windows.
Twenty-five children had to be admitted to the hospital. Treatment included lorazepam and salbutamol. All students had normal oxygen levels, and the symptoms were reversed.
Cough or Allergy?
The clinical differential diagnosis for an allergy is quite simple, said Dr. Elmer. Platanus cough mainly shows symptoms of irritation, a feeling of a foreign body, and scratching in the eyes, throat, and nose. Coughing can also occur. In an allergy, there is often a runny nose and itching in the eyes and nose. Such allergic symptoms do not occur with platanus cough.
It should also be noted that the sensitization rates for a platanus allergy in Germany range between 5% and 11%. “Having so many platanus allergy sufferers in one place was relatively unlikely,” said Dr. Elmer.
She expects an increase in cases of platanus cough, especially in cities with dense construction, such as in narrow schoolyards. High concentrations of platanus dust can occur, especially when it is warm, dry, and windy. “Platanus cough does not occur every time we walk under plane trees. It strongly depends on warmth, dryness, and wind,” said Dr. Elmer.
Patients can protect themselves by avoiding skin and mucous membrane contact under appropriate climatic conditions and by wearing protective glasses and masks. Leaves and branches should not be swept but vacuumed. “Under no circumstances should plane trees be cut down. We need trees, especially in cities,” said Dr. Elmer. Moreover, the trichomes act as biofilters for air pollutants. In critical environments such as schoolyards, seasonal spraying of plane trees with a mixture of apple pectin and water can prevent the star hair from breaking off.
Thunderstorm Asthma
For patients with asthma, wildfires, storms, heavy rainfall, and thunderstorms can lead to exacerbations. Emergency room visits and hospital admissions generally increase after extreme weather events.
A study examining the consequences of the fires in California from 2004 to 2009, for example, reported that hospital visits related to asthma increased by 10.3%. Those related to respiratory problems increased by 3.3%. Infants and children up to age 5 years were most affected.
Thunderstorms are increasing because of global warming. Thunderstorm asthma arises under specific meteorological conditions. It typically occurs in patients with aeroallergies (eg, to pollen and fungal spores) in combination with thunderstorms and lightning. Large pollen grains, which normally remain in the upper airways, ascend into higher atmospheric layers and break apart due to updrafts. These very small particles are pushed back to ground level by downdrafts, enter the lower airways, and cause acute asthma.
Worldwide, cases of thunderstorm asthma are rare. About 30 events have been documented. Thunderstorm asthma was first observed in 1983 in Birmingham, England. Fungal spores were the trigger.
The most significant incident so far was a severe thunderstorm on November 21, 2016, in Melbourne, Australia. Worldwide attention was drawn to the storm because of an unusually high number of asthma cases. Within 30 hours, 3365 patients were admitted to emergency rooms. “This is also a high burden for a city with 4.6 million inhabitants,” said Dr. Elmer. Of the patients in Melbourne, 35 were admitted to the intensive care unit and 5 patients died.
Dr. Elmer calculated the corresponding number of patients for Wiesbaden and Mainz. “Assuming a population of 500,000 in this region, that would be 400 patients in emergency rooms within 30 hours, which would be a significant number.”
Such events are mainly observed in Australia, where two events per decade are expected. However, due to climate change, the risk could also increase in Europe, leading to more cases of thunderstorm asthma.
Risk Factors
The following environmental factors increase the risk:
- High pollen concentrations in the days before a thunderstorm
- Precipitation and high humidity, thunderstorms, and lightning
- Sudden temperature changes
- Increases in aeroallergen biomass and extreme weather events because of climate change
In Australia, grass pollen was often the trigger for thunderstorm asthma. In the United Kingdom, it was fungal spores. In Italy, olive pollen has a similar potential.
Patients with preexisting asthma, uncontrolled asthma, and high serum-specific immunoglobulin E levels are at risk. The risk is also increased for patients with poor compliance with inhaled steroid (ICS) therapy and for patients who have previously been hospitalized because of their asthma.
Patients with hay fever (ie, seasonal allergic rhinitis) have a significantly higher risk. As Dr. Elmer observed, 88% of patients in the emergency room in Melbourne had seasonal allergic rhinitis. “Fifty-seven percent of the patients in the emergency room did not have previously known asthma, but more than half showed symptoms indicating latent asthma. These patients had latent asthma but had not yet been diagnosed.”
Dr. Elmer emphasized how important it is not to underestimate mild asthma, which should be treated. For patients with hay fever, hyposensitization should be considered.
Reducing Risk
Many factors must come together for thunderstorm asthma to develop, according to Dr. Elmer. Because this convergence is difficult to predict, however, preparation and risk reduction are important. They consist of individual precautions and public health strategies.
The following steps can be taken at the individual level:
- Identify risk groups, including patients with allergic rhinitis and high serum-specific immunoglobulin E levels. Patients with hay fever benefit from hyposensitization.
- Avoid outdoor activities on risky days.
- Diagnose asthma, and do not underestimate mild asthma. Improve therapy compliance with ICS therapy and use maintenance and reliever therapy. This way, the patient automatically increases the steroid dose with increased symptoms and is better protected against exacerbations.
- Improve health literacy and understanding of asthma.
Thunderstorm asthma also affects healthcare professionals, Dr. Elmer warned. In Melbourne, 25% of responders themselves showed symptoms. Therefore, expect that some of these clinicians will also be unavailable.
Other steps are appropriate at the public health level. In addition to monitoring local pollen concentrations, one must identify risk groups, especially people working outdoors. “It is very difficult to predict an epidemic of thunderstorm asthma,” said Dr. Elmer. Therefore, it is important to increase awareness of the phenomenon and to develop an early warning system with emergency plans for patients and the healthcare system.
“Allergen immunotherapy is protective,” she added. “This has been well studied, and for Melbourne, it has been demonstrated. Patients with allergic rhinitis who had received immunotherapy were protected. These patients did not have to visit the emergency room. This shows that we can do something, and we should hyposensitize,” Dr. Elmer concluded.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Because of climate change, heat waves, storms, heavy rainfalls, and floods are now occurring in areas that seldom experienced these phenomena before. “Extreme weather events are rare, but in terms of their extent, duration, and scale, they are unusual. And they are increasing due to climate change,” said Andrea Elmer, MD, an internal medicine and pulmonology specialist at the DKD Helios Clinic in Wiesbaden, Germany. She spoke at the Congress of the German Society for Pneumology and Respiratory Medicine.
Dr. Elmer referred to the 2023 status report by the Robert Koch Institute and the 2023 Synthesis Report by the Intergovernmental Panel on Climate Change, in which the likelihood of extreme weather events was acknowledged to be significantly higher than previously recognized. “Knowing about such extreme weather events is important to assess the consequences for our patients and to identify possible medical care needs,” said Dr. Elmer. She focused on the effects of platanus (plane tree) cough and thunderstorm asthma.
Platanus Cough
The symptoms worsened when the children left the building and waited in the schoolyard. Initially, a chemical attack with irritant gas was suspected because the school is located near an industrial area. There were no indications of a pollen cloud.
Eventually, doctors and firefighters found that the symptoms were caused by platanus cough, which is induced by the fine star-shaped hair found on young platanus leaves, bark, young branches, and buds. If strong winds move the leaves after prolonged dryness, these trichomes can break off when touched, creating platanus dust.
At that time, there were unusual climatic conditions. The temperature was 29 °C, it was dry, and wind gusts reached 50 km/h. The schoolyard was enclosed and densely planted with tall, old plane trees. Initial symptoms occurred in classrooms with open windows.
Twenty-five children had to be admitted to the hospital. Treatment included lorazepam and salbutamol. All students had normal oxygen levels, and the symptoms were reversed.
Cough or Allergy?
The clinical differential diagnosis for an allergy is quite simple, said Dr. Elmer. Platanus cough mainly shows symptoms of irritation, a feeling of a foreign body, and scratching in the eyes, throat, and nose. Coughing can also occur. In an allergy, there is often a runny nose and itching in the eyes and nose. Such allergic symptoms do not occur with platanus cough.
It should also be noted that the sensitization rates for a platanus allergy in Germany range between 5% and 11%. “Having so many platanus allergy sufferers in one place was relatively unlikely,” said Dr. Elmer.
She expects an increase in cases of platanus cough, especially in cities with dense construction, such as in narrow schoolyards. High concentrations of platanus dust can occur, especially when it is warm, dry, and windy. “Platanus cough does not occur every time we walk under plane trees. It strongly depends on warmth, dryness, and wind,” said Dr. Elmer.
Patients can protect themselves by avoiding skin and mucous membrane contact under appropriate climatic conditions and by wearing protective glasses and masks. Leaves and branches should not be swept but vacuumed. “Under no circumstances should plane trees be cut down. We need trees, especially in cities,” said Dr. Elmer. Moreover, the trichomes act as biofilters for air pollutants. In critical environments such as schoolyards, seasonal spraying of plane trees with a mixture of apple pectin and water can prevent the star hair from breaking off.
Thunderstorm Asthma
For patients with asthma, wildfires, storms, heavy rainfall, and thunderstorms can lead to exacerbations. Emergency room visits and hospital admissions generally increase after extreme weather events.
A study examining the consequences of the fires in California from 2004 to 2009, for example, reported that hospital visits related to asthma increased by 10.3%. Those related to respiratory problems increased by 3.3%. Infants and children up to age 5 years were most affected.
Thunderstorms are increasing because of global warming. Thunderstorm asthma arises under specific meteorological conditions. It typically occurs in patients with aeroallergies (eg, to pollen and fungal spores) in combination with thunderstorms and lightning. Large pollen grains, which normally remain in the upper airways, ascend into higher atmospheric layers and break apart due to updrafts. These very small particles are pushed back to ground level by downdrafts, enter the lower airways, and cause acute asthma.
Worldwide, cases of thunderstorm asthma are rare. About 30 events have been documented. Thunderstorm asthma was first observed in 1983 in Birmingham, England. Fungal spores were the trigger.
The most significant incident so far was a severe thunderstorm on November 21, 2016, in Melbourne, Australia. Worldwide attention was drawn to the storm because of an unusually high number of asthma cases. Within 30 hours, 3365 patients were admitted to emergency rooms. “This is also a high burden for a city with 4.6 million inhabitants,” said Dr. Elmer. Of the patients in Melbourne, 35 were admitted to the intensive care unit and 5 patients died.
Dr. Elmer calculated the corresponding number of patients for Wiesbaden and Mainz. “Assuming a population of 500,000 in this region, that would be 400 patients in emergency rooms within 30 hours, which would be a significant number.”
Such events are mainly observed in Australia, where two events per decade are expected. However, due to climate change, the risk could also increase in Europe, leading to more cases of thunderstorm asthma.
Risk Factors
The following environmental factors increase the risk:
- High pollen concentrations in the days before a thunderstorm
- Precipitation and high humidity, thunderstorms, and lightning
- Sudden temperature changes
- Increases in aeroallergen biomass and extreme weather events because of climate change
In Australia, grass pollen was often the trigger for thunderstorm asthma. In the United Kingdom, it was fungal spores. In Italy, olive pollen has a similar potential.
Patients with preexisting asthma, uncontrolled asthma, and high serum-specific immunoglobulin E levels are at risk. The risk is also increased for patients with poor compliance with inhaled steroid (ICS) therapy and for patients who have previously been hospitalized because of their asthma.
Patients with hay fever (ie, seasonal allergic rhinitis) have a significantly higher risk. As Dr. Elmer observed, 88% of patients in the emergency room in Melbourne had seasonal allergic rhinitis. “Fifty-seven percent of the patients in the emergency room did not have previously known asthma, but more than half showed symptoms indicating latent asthma. These patients had latent asthma but had not yet been diagnosed.”
Dr. Elmer emphasized how important it is not to underestimate mild asthma, which should be treated. For patients with hay fever, hyposensitization should be considered.
Reducing Risk
Many factors must come together for thunderstorm asthma to develop, according to Dr. Elmer. Because this convergence is difficult to predict, however, preparation and risk reduction are important. They consist of individual precautions and public health strategies.
The following steps can be taken at the individual level:
- Identify risk groups, including patients with allergic rhinitis and high serum-specific immunoglobulin E levels. Patients with hay fever benefit from hyposensitization.
- Avoid outdoor activities on risky days.
- Diagnose asthma, and do not underestimate mild asthma. Improve therapy compliance with ICS therapy and use maintenance and reliever therapy. This way, the patient automatically increases the steroid dose with increased symptoms and is better protected against exacerbations.
- Improve health literacy and understanding of asthma.
Thunderstorm asthma also affects healthcare professionals, Dr. Elmer warned. In Melbourne, 25% of responders themselves showed symptoms. Therefore, expect that some of these clinicians will also be unavailable.
Other steps are appropriate at the public health level. In addition to monitoring local pollen concentrations, one must identify risk groups, especially people working outdoors. “It is very difficult to predict an epidemic of thunderstorm asthma,” said Dr. Elmer. Therefore, it is important to increase awareness of the phenomenon and to develop an early warning system with emergency plans for patients and the healthcare system.
“Allergen immunotherapy is protective,” she added. “This has been well studied, and for Melbourne, it has been demonstrated. Patients with allergic rhinitis who had received immunotherapy were protected. These patients did not have to visit the emergency room. This shows that we can do something, and we should hyposensitize,” Dr. Elmer concluded.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Because of climate change, heat waves, storms, heavy rainfalls, and floods are now occurring in areas that seldom experienced these phenomena before. “Extreme weather events are rare, but in terms of their extent, duration, and scale, they are unusual. And they are increasing due to climate change,” said Andrea Elmer, MD, an internal medicine and pulmonology specialist at the DKD Helios Clinic in Wiesbaden, Germany. She spoke at the Congress of the German Society for Pneumology and Respiratory Medicine.
Dr. Elmer referred to the 2023 status report by the Robert Koch Institute and the 2023 Synthesis Report by the Intergovernmental Panel on Climate Change, in which the likelihood of extreme weather events was acknowledged to be significantly higher than previously recognized. “Knowing about such extreme weather events is important to assess the consequences for our patients and to identify possible medical care needs,” said Dr. Elmer. She focused on the effects of platanus (plane tree) cough and thunderstorm asthma.
Platanus Cough
The symptoms worsened when the children left the building and waited in the schoolyard. Initially, a chemical attack with irritant gas was suspected because the school is located near an industrial area. There were no indications of a pollen cloud.
Eventually, doctors and firefighters found that the symptoms were caused by platanus cough, which is induced by the fine star-shaped hair found on young platanus leaves, bark, young branches, and buds. If strong winds move the leaves after prolonged dryness, these trichomes can break off when touched, creating platanus dust.
At that time, there were unusual climatic conditions. The temperature was 29 °C, it was dry, and wind gusts reached 50 km/h. The schoolyard was enclosed and densely planted with tall, old plane trees. Initial symptoms occurred in classrooms with open windows.
Twenty-five children had to be admitted to the hospital. Treatment included lorazepam and salbutamol. All students had normal oxygen levels, and the symptoms were reversed.
Cough or Allergy?
The clinical differential diagnosis for an allergy is quite simple, said Dr. Elmer. Platanus cough mainly shows symptoms of irritation, a feeling of a foreign body, and scratching in the eyes, throat, and nose. Coughing can also occur. In an allergy, there is often a runny nose and itching in the eyes and nose. Such allergic symptoms do not occur with platanus cough.
It should also be noted that the sensitization rates for a platanus allergy in Germany range between 5% and 11%. “Having so many platanus allergy sufferers in one place was relatively unlikely,” said Dr. Elmer.
She expects an increase in cases of platanus cough, especially in cities with dense construction, such as in narrow schoolyards. High concentrations of platanus dust can occur, especially when it is warm, dry, and windy. “Platanus cough does not occur every time we walk under plane trees. It strongly depends on warmth, dryness, and wind,” said Dr. Elmer.
Patients can protect themselves by avoiding skin and mucous membrane contact under appropriate climatic conditions and by wearing protective glasses and masks. Leaves and branches should not be swept but vacuumed. “Under no circumstances should plane trees be cut down. We need trees, especially in cities,” said Dr. Elmer. Moreover, the trichomes act as biofilters for air pollutants. In critical environments such as schoolyards, seasonal spraying of plane trees with a mixture of apple pectin and water can prevent the star hair from breaking off.
Thunderstorm Asthma
For patients with asthma, wildfires, storms, heavy rainfall, and thunderstorms can lead to exacerbations. Emergency room visits and hospital admissions generally increase after extreme weather events.
A study examining the consequences of the fires in California from 2004 to 2009, for example, reported that hospital visits related to asthma increased by 10.3%. Those related to respiratory problems increased by 3.3%. Infants and children up to age 5 years were most affected.
Thunderstorms are increasing because of global warming. Thunderstorm asthma arises under specific meteorological conditions. It typically occurs in patients with aeroallergies (eg, to pollen and fungal spores) in combination with thunderstorms and lightning. Large pollen grains, which normally remain in the upper airways, ascend into higher atmospheric layers and break apart due to updrafts. These very small particles are pushed back to ground level by downdrafts, enter the lower airways, and cause acute asthma.
Worldwide, cases of thunderstorm asthma are rare. About 30 events have been documented. Thunderstorm asthma was first observed in 1983 in Birmingham, England. Fungal spores were the trigger.
The most significant incident so far was a severe thunderstorm on November 21, 2016, in Melbourne, Australia. Worldwide attention was drawn to the storm because of an unusually high number of asthma cases. Within 30 hours, 3365 patients were admitted to emergency rooms. “This is also a high burden for a city with 4.6 million inhabitants,” said Dr. Elmer. Of the patients in Melbourne, 35 were admitted to the intensive care unit and 5 patients died.
Dr. Elmer calculated the corresponding number of patients for Wiesbaden and Mainz. “Assuming a population of 500,000 in this region, that would be 400 patients in emergency rooms within 30 hours, which would be a significant number.”
Such events are mainly observed in Australia, where two events per decade are expected. However, due to climate change, the risk could also increase in Europe, leading to more cases of thunderstorm asthma.
Risk Factors
The following environmental factors increase the risk:
- High pollen concentrations in the days before a thunderstorm
- Precipitation and high humidity, thunderstorms, and lightning
- Sudden temperature changes
- Increases in aeroallergen biomass and extreme weather events because of climate change
In Australia, grass pollen was often the trigger for thunderstorm asthma. In the United Kingdom, it was fungal spores. In Italy, olive pollen has a similar potential.
Patients with preexisting asthma, uncontrolled asthma, and high serum-specific immunoglobulin E levels are at risk. The risk is also increased for patients with poor compliance with inhaled steroid (ICS) therapy and for patients who have previously been hospitalized because of their asthma.
Patients with hay fever (ie, seasonal allergic rhinitis) have a significantly higher risk. As Dr. Elmer observed, 88% of patients in the emergency room in Melbourne had seasonal allergic rhinitis. “Fifty-seven percent of the patients in the emergency room did not have previously known asthma, but more than half showed symptoms indicating latent asthma. These patients had latent asthma but had not yet been diagnosed.”
Dr. Elmer emphasized how important it is not to underestimate mild asthma, which should be treated. For patients with hay fever, hyposensitization should be considered.
Reducing Risk
Many factors must come together for thunderstorm asthma to develop, according to Dr. Elmer. Because this convergence is difficult to predict, however, preparation and risk reduction are important. They consist of individual precautions and public health strategies.
The following steps can be taken at the individual level:
- Identify risk groups, including patients with allergic rhinitis and high serum-specific immunoglobulin E levels. Patients with hay fever benefit from hyposensitization.
- Avoid outdoor activities on risky days.
- Diagnose asthma, and do not underestimate mild asthma. Improve therapy compliance with ICS therapy and use maintenance and reliever therapy. This way, the patient automatically increases the steroid dose with increased symptoms and is better protected against exacerbations.
- Improve health literacy and understanding of asthma.
Thunderstorm asthma also affects healthcare professionals, Dr. Elmer warned. In Melbourne, 25% of responders themselves showed symptoms. Therefore, expect that some of these clinicians will also be unavailable.
Other steps are appropriate at the public health level. In addition to monitoring local pollen concentrations, one must identify risk groups, especially people working outdoors. “It is very difficult to predict an epidemic of thunderstorm asthma,” said Dr. Elmer. Therefore, it is important to increase awareness of the phenomenon and to develop an early warning system with emergency plans for patients and the healthcare system.
“Allergen immunotherapy is protective,” she added. “This has been well studied, and for Melbourne, it has been demonstrated. Patients with allergic rhinitis who had received immunotherapy were protected. These patients did not have to visit the emergency room. This shows that we can do something, and we should hyposensitize,” Dr. Elmer concluded.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
New Trial Deepens Debate Over Late-Preterm Steroids
The early cancellation of a trial in southern India suggests that the use of antenatal steroids to prevent respiratory complications after late-preterm birth — a recommended practice in the United States — may not be effective in the developing world.
As reported in Obstetrics & Gynecology, researchers led by Hilda Yenuberi, MD, of Christian Medical College, Vellore, Tamil Nadu, India, stopped the randomized, triple-blinded, placebo-controlled CLAP (Corticosteroids in Late Pregnancy) study at 70% enrollment. An interim analysis found no benefit from prescribing betamethasone vs placebo to women at risk of late-preterm delivery between 34 and 36 and 6/7 weeks of gestation (primary outcome of respiratory distress: 4.9% vs 4.8%, respectively, relative risk [RR], 1.03; 95% CI, 0.57-1.84; number needed to treat = 786).
“These findings may suggest differing efficacy of antenatal corticosteroids in developing countries compared with developed countries ... that should be considered when late-preterm antenatal corticosteroids are administered,” the researchers wrote.
The use of steroids in patients at risk of delivery before 34 weeks is widely accepted as a way to prevent neonatal respiratory distress, a common and potentially deadly condition in premature infants whose lungs are not fully developed. However, there’s debate over steroid treatment in women who are expected to deliver later than 34 weeks but still preterm.
As the study notes, “the American College of Obstetricians and Gynecologists recommends a single course of betamethasone for pregnant individuals at risk of delivering between 34 and 36 6/7 weeks of gestation on the basis of the ALPS (Antenatal Late Preterm Steroid) trial.”
But other randomized trials have reached different conclusions, and steroids are not without risks. Studies have linked prenatal steroids to neurosensory disorders in babies, meaning they’re more likely to need hearing aids and eyeglasses, said Kellie Murphy, MD, MSc, professor of obstetrics and gynecology, University of Toronto, Toronto, Ontario, Canada, in an interview. Dr. Murphy, who was not involved in the new trial, added that there are links between steroids and greater likelihood of poorer performance in school,
For the new study, conducted from 2020 to 2022 at Christian Medical College and Hospital in Vellore, India, researchers randomly assigned 423 patients to betamethasone (410 in the interim analysis; average age, 26.8 years) and 424 to placebo (415 in the interim analysis; average age, 26.2 years).
The average age of participants was 26.8 years. All were between 34 and 36 6/7 weeks of gestation and expected to give birth within the next week. A quarter of participants delivered at term, which the authors wrote “may have influenced the primary outcome.” The total number of neonates was 883, including 58 twin pregnancies.
There was no significant difference in respiratory distress between groups, “defined as need for oxygen or continuous positive airway pressure or mechanical ventilation for at least 2 hours in the first 72 hours of life.” There also were no significant differences in maternal outcomes such as chorioamnionitis or length of hospitalization or neonatal secondary outcomes such as transient tachypnea of the newborn, respiratory distress syndrome, necrotizing enterocolitis, sepsis, hyperbilirubinemia, stillbirth, and early neonatal death.
Serious adverse events occurred in four neonates but none were linked to the intervention.
The study doesn’t discuss cost, but a 2019 report suggests that use of betamethasone to prevent neonatal respiratory distress is cost-effective.
“Our findings are contradictory to those of a systematic review, the major contributor of which was the ALPS trial,” the authors of the new study reported. “The primary outcome of the ALPS trial, the composite of neonatal treatment in the first 72 hours, was significantly less in the group who received betamethasone (11.6%), compared with the placebo group (14.4%; relative risk [RR], 0.80; 95% CI, 0.66-0.97).”
The study authors, who didn’t respond to requests for comment, noted that their trial included twin pregnancies and patients with gestational diabetes; the ALPS trial did not.
Perinatologist Cynthia Gyamfi-Bannerman, MD, MS, chair and professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California,San Diego, and principal investigator of the ALPS study, said in an interview that the inclusion of twins in the new trial is “a fundamental flaw.”
“Because antenatal corticosteroids have not been shown to be useful in twins at any gestational age, it is not surprising that including twins likely moved the findings to the null in this study,” she said. “Twins were purposefully excluded from the ALPS trial for this reason.”
According to the new study, “the primary outcome among singleton neonates occurred in 4.8% (18/374) who received betamethasone and 5.1% (20/393) who received placebo (RR, 0.94; 95% CI, 0.51-1.75)
What should clinicians take from the study findings? In an accompanying commentary, Blair J. Wylie, MD, MPH, of Columbia University Medical Center, New York, NY, and Syed Asad Ali, MBBS, MPH, of Aga Khan University, Karachi, Pakistan, wrote that, “in settings similar to the US-based ALPS trial, the practice of administering a course of late-preterm antenatal corticosteroids should be continued, as espoused by our professional organizations.”
However, the new study suggests that “research in high-resource environments may not be generalizable to low-resource settings,” they write.
Neonatologist Elizabeth Asztalos, MD, MSc, an associate scientist with Sunnybrook Health Sciences Center in Toronto, Canada, said in an interview that she doesn’t worry about pregnant mothers not getting steroids later than 34 weeks. “We have tools in our armamentarium in the NICU setting to help babies if they need it,” said Dr. Asztalos, who didn’t take part in the new trial. “We can put them on CPAP if they have wet lung. If they have an element of respiratory distress, we can give them surfactants. These bigger babies have more ability to recover from all this compared to a baby who was born at 24, 25, 26 weeks.”
For her part, the University of Toronto’s Dr. Murphy said decision-making about late-preterm steroids is complicated. “You don’t want to miss the opportunity to give to provide benefits for the patients” via steroids, she said. “But on the flip side, it’s a double-edged sword. It’s not easy. It’s not straightforward.”
In the big picture, she said, “people need to be really clear why they’re giving an intervention and what they hope to achieve.”
Christian Medical College supported the study. The authors, Dr. Murphy, Dr. Asztalos, and commentary co-author Dr. Ali have no disclosures. Dr. Gyamfi-Bannerman discloses being principal investigator of the ALPS trial. Commentary co-author Dr. Wylie serves on the ultrasound quality assurance committee of a trial discussed in the commentary.
The early cancellation of a trial in southern India suggests that the use of antenatal steroids to prevent respiratory complications after late-preterm birth — a recommended practice in the United States — may not be effective in the developing world.
As reported in Obstetrics & Gynecology, researchers led by Hilda Yenuberi, MD, of Christian Medical College, Vellore, Tamil Nadu, India, stopped the randomized, triple-blinded, placebo-controlled CLAP (Corticosteroids in Late Pregnancy) study at 70% enrollment. An interim analysis found no benefit from prescribing betamethasone vs placebo to women at risk of late-preterm delivery between 34 and 36 and 6/7 weeks of gestation (primary outcome of respiratory distress: 4.9% vs 4.8%, respectively, relative risk [RR], 1.03; 95% CI, 0.57-1.84; number needed to treat = 786).
“These findings may suggest differing efficacy of antenatal corticosteroids in developing countries compared with developed countries ... that should be considered when late-preterm antenatal corticosteroids are administered,” the researchers wrote.
The use of steroids in patients at risk of delivery before 34 weeks is widely accepted as a way to prevent neonatal respiratory distress, a common and potentially deadly condition in premature infants whose lungs are not fully developed. However, there’s debate over steroid treatment in women who are expected to deliver later than 34 weeks but still preterm.
As the study notes, “the American College of Obstetricians and Gynecologists recommends a single course of betamethasone for pregnant individuals at risk of delivering between 34 and 36 6/7 weeks of gestation on the basis of the ALPS (Antenatal Late Preterm Steroid) trial.”
But other randomized trials have reached different conclusions, and steroids are not without risks. Studies have linked prenatal steroids to neurosensory disorders in babies, meaning they’re more likely to need hearing aids and eyeglasses, said Kellie Murphy, MD, MSc, professor of obstetrics and gynecology, University of Toronto, Toronto, Ontario, Canada, in an interview. Dr. Murphy, who was not involved in the new trial, added that there are links between steroids and greater likelihood of poorer performance in school,
For the new study, conducted from 2020 to 2022 at Christian Medical College and Hospital in Vellore, India, researchers randomly assigned 423 patients to betamethasone (410 in the interim analysis; average age, 26.8 years) and 424 to placebo (415 in the interim analysis; average age, 26.2 years).
The average age of participants was 26.8 years. All were between 34 and 36 6/7 weeks of gestation and expected to give birth within the next week. A quarter of participants delivered at term, which the authors wrote “may have influenced the primary outcome.” The total number of neonates was 883, including 58 twin pregnancies.
There was no significant difference in respiratory distress between groups, “defined as need for oxygen or continuous positive airway pressure or mechanical ventilation for at least 2 hours in the first 72 hours of life.” There also were no significant differences in maternal outcomes such as chorioamnionitis or length of hospitalization or neonatal secondary outcomes such as transient tachypnea of the newborn, respiratory distress syndrome, necrotizing enterocolitis, sepsis, hyperbilirubinemia, stillbirth, and early neonatal death.
Serious adverse events occurred in four neonates but none were linked to the intervention.
The study doesn’t discuss cost, but a 2019 report suggests that use of betamethasone to prevent neonatal respiratory distress is cost-effective.
“Our findings are contradictory to those of a systematic review, the major contributor of which was the ALPS trial,” the authors of the new study reported. “The primary outcome of the ALPS trial, the composite of neonatal treatment in the first 72 hours, was significantly less in the group who received betamethasone (11.6%), compared with the placebo group (14.4%; relative risk [RR], 0.80; 95% CI, 0.66-0.97).”
The study authors, who didn’t respond to requests for comment, noted that their trial included twin pregnancies and patients with gestational diabetes; the ALPS trial did not.
Perinatologist Cynthia Gyamfi-Bannerman, MD, MS, chair and professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California,San Diego, and principal investigator of the ALPS study, said in an interview that the inclusion of twins in the new trial is “a fundamental flaw.”
“Because antenatal corticosteroids have not been shown to be useful in twins at any gestational age, it is not surprising that including twins likely moved the findings to the null in this study,” she said. “Twins were purposefully excluded from the ALPS trial for this reason.”
According to the new study, “the primary outcome among singleton neonates occurred in 4.8% (18/374) who received betamethasone and 5.1% (20/393) who received placebo (RR, 0.94; 95% CI, 0.51-1.75)
What should clinicians take from the study findings? In an accompanying commentary, Blair J. Wylie, MD, MPH, of Columbia University Medical Center, New York, NY, and Syed Asad Ali, MBBS, MPH, of Aga Khan University, Karachi, Pakistan, wrote that, “in settings similar to the US-based ALPS trial, the practice of administering a course of late-preterm antenatal corticosteroids should be continued, as espoused by our professional organizations.”
However, the new study suggests that “research in high-resource environments may not be generalizable to low-resource settings,” they write.
Neonatologist Elizabeth Asztalos, MD, MSc, an associate scientist with Sunnybrook Health Sciences Center in Toronto, Canada, said in an interview that she doesn’t worry about pregnant mothers not getting steroids later than 34 weeks. “We have tools in our armamentarium in the NICU setting to help babies if they need it,” said Dr. Asztalos, who didn’t take part in the new trial. “We can put them on CPAP if they have wet lung. If they have an element of respiratory distress, we can give them surfactants. These bigger babies have more ability to recover from all this compared to a baby who was born at 24, 25, 26 weeks.”
For her part, the University of Toronto’s Dr. Murphy said decision-making about late-preterm steroids is complicated. “You don’t want to miss the opportunity to give to provide benefits for the patients” via steroids, she said. “But on the flip side, it’s a double-edged sword. It’s not easy. It’s not straightforward.”
In the big picture, she said, “people need to be really clear why they’re giving an intervention and what they hope to achieve.”
Christian Medical College supported the study. The authors, Dr. Murphy, Dr. Asztalos, and commentary co-author Dr. Ali have no disclosures. Dr. Gyamfi-Bannerman discloses being principal investigator of the ALPS trial. Commentary co-author Dr. Wylie serves on the ultrasound quality assurance committee of a trial discussed in the commentary.
The early cancellation of a trial in southern India suggests that the use of antenatal steroids to prevent respiratory complications after late-preterm birth — a recommended practice in the United States — may not be effective in the developing world.
As reported in Obstetrics & Gynecology, researchers led by Hilda Yenuberi, MD, of Christian Medical College, Vellore, Tamil Nadu, India, stopped the randomized, triple-blinded, placebo-controlled CLAP (Corticosteroids in Late Pregnancy) study at 70% enrollment. An interim analysis found no benefit from prescribing betamethasone vs placebo to women at risk of late-preterm delivery between 34 and 36 and 6/7 weeks of gestation (primary outcome of respiratory distress: 4.9% vs 4.8%, respectively, relative risk [RR], 1.03; 95% CI, 0.57-1.84; number needed to treat = 786).
“These findings may suggest differing efficacy of antenatal corticosteroids in developing countries compared with developed countries ... that should be considered when late-preterm antenatal corticosteroids are administered,” the researchers wrote.
The use of steroids in patients at risk of delivery before 34 weeks is widely accepted as a way to prevent neonatal respiratory distress, a common and potentially deadly condition in premature infants whose lungs are not fully developed. However, there’s debate over steroid treatment in women who are expected to deliver later than 34 weeks but still preterm.
As the study notes, “the American College of Obstetricians and Gynecologists recommends a single course of betamethasone for pregnant individuals at risk of delivering between 34 and 36 6/7 weeks of gestation on the basis of the ALPS (Antenatal Late Preterm Steroid) trial.”
But other randomized trials have reached different conclusions, and steroids are not without risks. Studies have linked prenatal steroids to neurosensory disorders in babies, meaning they’re more likely to need hearing aids and eyeglasses, said Kellie Murphy, MD, MSc, professor of obstetrics and gynecology, University of Toronto, Toronto, Ontario, Canada, in an interview. Dr. Murphy, who was not involved in the new trial, added that there are links between steroids and greater likelihood of poorer performance in school,
For the new study, conducted from 2020 to 2022 at Christian Medical College and Hospital in Vellore, India, researchers randomly assigned 423 patients to betamethasone (410 in the interim analysis; average age, 26.8 years) and 424 to placebo (415 in the interim analysis; average age, 26.2 years).
The average age of participants was 26.8 years. All were between 34 and 36 6/7 weeks of gestation and expected to give birth within the next week. A quarter of participants delivered at term, which the authors wrote “may have influenced the primary outcome.” The total number of neonates was 883, including 58 twin pregnancies.
There was no significant difference in respiratory distress between groups, “defined as need for oxygen or continuous positive airway pressure or mechanical ventilation for at least 2 hours in the first 72 hours of life.” There also were no significant differences in maternal outcomes such as chorioamnionitis or length of hospitalization or neonatal secondary outcomes such as transient tachypnea of the newborn, respiratory distress syndrome, necrotizing enterocolitis, sepsis, hyperbilirubinemia, stillbirth, and early neonatal death.
Serious adverse events occurred in four neonates but none were linked to the intervention.
The study doesn’t discuss cost, but a 2019 report suggests that use of betamethasone to prevent neonatal respiratory distress is cost-effective.
“Our findings are contradictory to those of a systematic review, the major contributor of which was the ALPS trial,” the authors of the new study reported. “The primary outcome of the ALPS trial, the composite of neonatal treatment in the first 72 hours, was significantly less in the group who received betamethasone (11.6%), compared with the placebo group (14.4%; relative risk [RR], 0.80; 95% CI, 0.66-0.97).”
The study authors, who didn’t respond to requests for comment, noted that their trial included twin pregnancies and patients with gestational diabetes; the ALPS trial did not.
Perinatologist Cynthia Gyamfi-Bannerman, MD, MS, chair and professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California,San Diego, and principal investigator of the ALPS study, said in an interview that the inclusion of twins in the new trial is “a fundamental flaw.”
“Because antenatal corticosteroids have not been shown to be useful in twins at any gestational age, it is not surprising that including twins likely moved the findings to the null in this study,” she said. “Twins were purposefully excluded from the ALPS trial for this reason.”
According to the new study, “the primary outcome among singleton neonates occurred in 4.8% (18/374) who received betamethasone and 5.1% (20/393) who received placebo (RR, 0.94; 95% CI, 0.51-1.75)
What should clinicians take from the study findings? In an accompanying commentary, Blair J. Wylie, MD, MPH, of Columbia University Medical Center, New York, NY, and Syed Asad Ali, MBBS, MPH, of Aga Khan University, Karachi, Pakistan, wrote that, “in settings similar to the US-based ALPS trial, the practice of administering a course of late-preterm antenatal corticosteroids should be continued, as espoused by our professional organizations.”
However, the new study suggests that “research in high-resource environments may not be generalizable to low-resource settings,” they write.
Neonatologist Elizabeth Asztalos, MD, MSc, an associate scientist with Sunnybrook Health Sciences Center in Toronto, Canada, said in an interview that she doesn’t worry about pregnant mothers not getting steroids later than 34 weeks. “We have tools in our armamentarium in the NICU setting to help babies if they need it,” said Dr. Asztalos, who didn’t take part in the new trial. “We can put them on CPAP if they have wet lung. If they have an element of respiratory distress, we can give them surfactants. These bigger babies have more ability to recover from all this compared to a baby who was born at 24, 25, 26 weeks.”
For her part, the University of Toronto’s Dr. Murphy said decision-making about late-preterm steroids is complicated. “You don’t want to miss the opportunity to give to provide benefits for the patients” via steroids, she said. “But on the flip side, it’s a double-edged sword. It’s not easy. It’s not straightforward.”
In the big picture, she said, “people need to be really clear why they’re giving an intervention and what they hope to achieve.”
Christian Medical College supported the study. The authors, Dr. Murphy, Dr. Asztalos, and commentary co-author Dr. Ali have no disclosures. Dr. Gyamfi-Bannerman discloses being principal investigator of the ALPS trial. Commentary co-author Dr. Wylie serves on the ultrasound quality assurance committee of a trial discussed in the commentary.
FROM OBSTETRICS & GYNECOLOGY
Antibiotics of Little Benefit in Lower Respiratory Tract Infection
Antibiotics had no measurable effect on the severity or duration of coughs due to acute lower respiratory tract infection (LRTI, or acute bronchitis), a large prospective study found.
In fact, those receiving an antibiotic in the primary- and urgent-care setting had a small but significant increase in overall length of illness (17.5 vs 15.9 days; P = .05) — largely because patients with longer illness before the index visit were more likely to receive these drugs. The study adds further support for reducing the prescription of antibiotics for LRTIs.
“Importantly, the pathogen data demonstrated that the length of time until illness resolution for those with bacterial infection was the same as for those not receiving an antibiotic versus those receiving one (17.3 vs 17.4 days),” researchers led by Daniel J. Merenstein, MD, a professor and director of research programs, family medicine, at Georgetown University Medical Center in Washington, wrote in the Journal of General Internal Medicine (doi: 10.1007/s11606-024-08758-y).
Patients believed an antibiotic would shorten their illness by an average of about 4 days, from 13.4 days to 9.7 days, whereas the average duration of all coughs was more than 2 weeks regardless of pathogen type or receipt of an antibiotic.
“Patients had unrealistic expectations regarding the duration of LRTI and the effect of antibiotics, which should be the target of antibiotic stewardship efforts,” the group wrote.
LRTIs can, however, be dangerous, with 3%-5% progressing to pneumonia, “but not everyone has easy access at an initial visit to an x-ray, which may be the reason clinicians still give antibiotics without any other evidence of a bacterial infection,” Dr. Merenstein said in a news release. “Patients have come to expect antibiotics for a cough, even if it doesn’t help. Basic symptom-relieving medications plus time bring a resolution to most people’s infections.”
The authors noted that cough is the most common reason for an ambulatory care visit, accounting for 2.7 million outpatient visits and more than 4 million emergency department visits annually.
Risks
Overuse of antibiotics can result in dizziness, nausea, diarrhea, and rash, along with a roughly 4% chance of serious adverse effects including anaphylaxis; Stevens-Johnson syndrome, a serious skin and mucous membrane disorder; and Clostridioides difficile-associated diarrhea.
An estimated half of all antibiotic prescriptions for acute respiratory conditions are unnecessary. Before the COVID-19 pandemic, antibiotics were prescribed about 70% of the time for a diagnosis of uncomplicated cough and LRTI. The viral pandemic did not change this practice according to a meta-analysis of 130 studies showing that 78% of COVID-19 patients were prescribed an antibiotic.
The study
The study looked at a cohort of 718 patients, with a mean age of 38.9 years, 65.3% female, of whom 207 received an antibiotic and 511 did not. Of those with baseline data, 29% had an antibiotic prescribed at baseline, the most common (in 85%) being amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin. Antibiotics had no effect on the duration or overall severity of cough in viral, bacterial, or mixed infections. Receipt of an antibiotic did, however, reduce the likelihood of a follow-up visit: 14.1% vs 8.2% (adjusted odds ratio, 0.47; 95% confidence interval, 0.26-0.84) — perhaps because it removed the motivation for seeking another consultation. Antibiotic recipients were more likely to receive a systemic corticosteroid (31.9% vs 4.5%, P <.001) and were also more likely to receive an albuterol inhaler (22.7% vs 7.6%, P <.001).
Jeffrey A. Linder, MD, MPH, a primary care physician and chief of internal medicine and geriatrics at Northwestern University Feinberg School of Medicine in Chicago, agrees that in the vast majority of LRTIs — usually acute bronchitis — antibiotics do not speed the healing process. “Forty years of research show that antibiotics do not make acute bronchitis go away any faster,” Dr. Linder, who was not involved in the current study, said in an interview. “There’s even growing evidence that a lot of pneumonia is viral as well, and 10 or 20 years from now we may often not be giving antibiotics for pneumonia because we’ll be able to see better if it’s caused by a virus.”
A large 2018 review by Dr. Linder and associates reported that 46% of antibiotics were prescribed without any infection-related diagnosis code and 20% without an office visit.
Dr. Linder routinely informs patients requesting an antibiotic about the risks of putting an ineffective chemical into their body. “I stress that it can cause rash and other allergic reactions, and even promote C diff infection,” he said. “And I also say it messes with the good bacteria in the microbiome, and they usually come around.”
Patients need to know, Dr. Linder added, that the normal course of healing the respiratory tract after acute bronchitis takes weeks. While a wet cough with sputum or phlegm will last a few days, it’s replaced with a dry annoying cough that persists for up to 3 weeks. “As long as they’re feeling generally better, that cough is normal,” he said. “A virus has run roughshod over their airways and they need a long time to heal and the cough is part of the healing process. Think how long it takes to heal a cut on a finger.”
In an era of escalating antimicrobial resistance fueled by antibiotic overuse, it’s become increasingly important to reserve antibiotics for necessary cases. According to a recent World Health Organization call to action, “Uncontrolled antimicrobial resistance is expected to lower life expectancy and lead to unprecedented health expenditure and economic losses.”
That said, there is important clinical work to be done to determine if there is a limited role for antibiotics in patients with cough, perhaps based on age and baseline severity. “Serious cough symptoms and how to treat them properly needs to be studied more, perhaps in a randomized clinical trial as this study was observational and there haven’t been any randomized trials looking at this issue since about 2012,” Dr. Merenstein said.
This research was funded by the Agency for Healthcare Research and Quality. The authors have no conflicts of interest to declare. Dr. Linder reported stock ownership in pharmaceutical companies but none that make antibiotics or other infectious disease drugs.
Antibiotics had no measurable effect on the severity or duration of coughs due to acute lower respiratory tract infection (LRTI, or acute bronchitis), a large prospective study found.
In fact, those receiving an antibiotic in the primary- and urgent-care setting had a small but significant increase in overall length of illness (17.5 vs 15.9 days; P = .05) — largely because patients with longer illness before the index visit were more likely to receive these drugs. The study adds further support for reducing the prescription of antibiotics for LRTIs.
“Importantly, the pathogen data demonstrated that the length of time until illness resolution for those with bacterial infection was the same as for those not receiving an antibiotic versus those receiving one (17.3 vs 17.4 days),” researchers led by Daniel J. Merenstein, MD, a professor and director of research programs, family medicine, at Georgetown University Medical Center in Washington, wrote in the Journal of General Internal Medicine (doi: 10.1007/s11606-024-08758-y).
Patients believed an antibiotic would shorten their illness by an average of about 4 days, from 13.4 days to 9.7 days, whereas the average duration of all coughs was more than 2 weeks regardless of pathogen type or receipt of an antibiotic.
“Patients had unrealistic expectations regarding the duration of LRTI and the effect of antibiotics, which should be the target of antibiotic stewardship efforts,” the group wrote.
LRTIs can, however, be dangerous, with 3%-5% progressing to pneumonia, “but not everyone has easy access at an initial visit to an x-ray, which may be the reason clinicians still give antibiotics without any other evidence of a bacterial infection,” Dr. Merenstein said in a news release. “Patients have come to expect antibiotics for a cough, even if it doesn’t help. Basic symptom-relieving medications plus time bring a resolution to most people’s infections.”
The authors noted that cough is the most common reason for an ambulatory care visit, accounting for 2.7 million outpatient visits and more than 4 million emergency department visits annually.
Risks
Overuse of antibiotics can result in dizziness, nausea, diarrhea, and rash, along with a roughly 4% chance of serious adverse effects including anaphylaxis; Stevens-Johnson syndrome, a serious skin and mucous membrane disorder; and Clostridioides difficile-associated diarrhea.
An estimated half of all antibiotic prescriptions for acute respiratory conditions are unnecessary. Before the COVID-19 pandemic, antibiotics were prescribed about 70% of the time for a diagnosis of uncomplicated cough and LRTI. The viral pandemic did not change this practice according to a meta-analysis of 130 studies showing that 78% of COVID-19 patients were prescribed an antibiotic.
The study
The study looked at a cohort of 718 patients, with a mean age of 38.9 years, 65.3% female, of whom 207 received an antibiotic and 511 did not. Of those with baseline data, 29% had an antibiotic prescribed at baseline, the most common (in 85%) being amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin. Antibiotics had no effect on the duration or overall severity of cough in viral, bacterial, or mixed infections. Receipt of an antibiotic did, however, reduce the likelihood of a follow-up visit: 14.1% vs 8.2% (adjusted odds ratio, 0.47; 95% confidence interval, 0.26-0.84) — perhaps because it removed the motivation for seeking another consultation. Antibiotic recipients were more likely to receive a systemic corticosteroid (31.9% vs 4.5%, P <.001) and were also more likely to receive an albuterol inhaler (22.7% vs 7.6%, P <.001).
Jeffrey A. Linder, MD, MPH, a primary care physician and chief of internal medicine and geriatrics at Northwestern University Feinberg School of Medicine in Chicago, agrees that in the vast majority of LRTIs — usually acute bronchitis — antibiotics do not speed the healing process. “Forty years of research show that antibiotics do not make acute bronchitis go away any faster,” Dr. Linder, who was not involved in the current study, said in an interview. “There’s even growing evidence that a lot of pneumonia is viral as well, and 10 or 20 years from now we may often not be giving antibiotics for pneumonia because we’ll be able to see better if it’s caused by a virus.”
A large 2018 review by Dr. Linder and associates reported that 46% of antibiotics were prescribed without any infection-related diagnosis code and 20% without an office visit.
Dr. Linder routinely informs patients requesting an antibiotic about the risks of putting an ineffective chemical into their body. “I stress that it can cause rash and other allergic reactions, and even promote C diff infection,” he said. “And I also say it messes with the good bacteria in the microbiome, and they usually come around.”
Patients need to know, Dr. Linder added, that the normal course of healing the respiratory tract after acute bronchitis takes weeks. While a wet cough with sputum or phlegm will last a few days, it’s replaced with a dry annoying cough that persists for up to 3 weeks. “As long as they’re feeling generally better, that cough is normal,” he said. “A virus has run roughshod over their airways and they need a long time to heal and the cough is part of the healing process. Think how long it takes to heal a cut on a finger.”
In an era of escalating antimicrobial resistance fueled by antibiotic overuse, it’s become increasingly important to reserve antibiotics for necessary cases. According to a recent World Health Organization call to action, “Uncontrolled antimicrobial resistance is expected to lower life expectancy and lead to unprecedented health expenditure and economic losses.”
That said, there is important clinical work to be done to determine if there is a limited role for antibiotics in patients with cough, perhaps based on age and baseline severity. “Serious cough symptoms and how to treat them properly needs to be studied more, perhaps in a randomized clinical trial as this study was observational and there haven’t been any randomized trials looking at this issue since about 2012,” Dr. Merenstein said.
This research was funded by the Agency for Healthcare Research and Quality. The authors have no conflicts of interest to declare. Dr. Linder reported stock ownership in pharmaceutical companies but none that make antibiotics or other infectious disease drugs.
Antibiotics had no measurable effect on the severity or duration of coughs due to acute lower respiratory tract infection (LRTI, or acute bronchitis), a large prospective study found.
In fact, those receiving an antibiotic in the primary- and urgent-care setting had a small but significant increase in overall length of illness (17.5 vs 15.9 days; P = .05) — largely because patients with longer illness before the index visit were more likely to receive these drugs. The study adds further support for reducing the prescription of antibiotics for LRTIs.
“Importantly, the pathogen data demonstrated that the length of time until illness resolution for those with bacterial infection was the same as for those not receiving an antibiotic versus those receiving one (17.3 vs 17.4 days),” researchers led by Daniel J. Merenstein, MD, a professor and director of research programs, family medicine, at Georgetown University Medical Center in Washington, wrote in the Journal of General Internal Medicine (doi: 10.1007/s11606-024-08758-y).
Patients believed an antibiotic would shorten their illness by an average of about 4 days, from 13.4 days to 9.7 days, whereas the average duration of all coughs was more than 2 weeks regardless of pathogen type or receipt of an antibiotic.
“Patients had unrealistic expectations regarding the duration of LRTI and the effect of antibiotics, which should be the target of antibiotic stewardship efforts,” the group wrote.
LRTIs can, however, be dangerous, with 3%-5% progressing to pneumonia, “but not everyone has easy access at an initial visit to an x-ray, which may be the reason clinicians still give antibiotics without any other evidence of a bacterial infection,” Dr. Merenstein said in a news release. “Patients have come to expect antibiotics for a cough, even if it doesn’t help. Basic symptom-relieving medications plus time bring a resolution to most people’s infections.”
The authors noted that cough is the most common reason for an ambulatory care visit, accounting for 2.7 million outpatient visits and more than 4 million emergency department visits annually.
Risks
Overuse of antibiotics can result in dizziness, nausea, diarrhea, and rash, along with a roughly 4% chance of serious adverse effects including anaphylaxis; Stevens-Johnson syndrome, a serious skin and mucous membrane disorder; and Clostridioides difficile-associated diarrhea.
An estimated half of all antibiotic prescriptions for acute respiratory conditions are unnecessary. Before the COVID-19 pandemic, antibiotics were prescribed about 70% of the time for a diagnosis of uncomplicated cough and LRTI. The viral pandemic did not change this practice according to a meta-analysis of 130 studies showing that 78% of COVID-19 patients were prescribed an antibiotic.
The study
The study looked at a cohort of 718 patients, with a mean age of 38.9 years, 65.3% female, of whom 207 received an antibiotic and 511 did not. Of those with baseline data, 29% had an antibiotic prescribed at baseline, the most common (in 85%) being amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin. Antibiotics had no effect on the duration or overall severity of cough in viral, bacterial, or mixed infections. Receipt of an antibiotic did, however, reduce the likelihood of a follow-up visit: 14.1% vs 8.2% (adjusted odds ratio, 0.47; 95% confidence interval, 0.26-0.84) — perhaps because it removed the motivation for seeking another consultation. Antibiotic recipients were more likely to receive a systemic corticosteroid (31.9% vs 4.5%, P <.001) and were also more likely to receive an albuterol inhaler (22.7% vs 7.6%, P <.001).
Jeffrey A. Linder, MD, MPH, a primary care physician and chief of internal medicine and geriatrics at Northwestern University Feinberg School of Medicine in Chicago, agrees that in the vast majority of LRTIs — usually acute bronchitis — antibiotics do not speed the healing process. “Forty years of research show that antibiotics do not make acute bronchitis go away any faster,” Dr. Linder, who was not involved in the current study, said in an interview. “There’s even growing evidence that a lot of pneumonia is viral as well, and 10 or 20 years from now we may often not be giving antibiotics for pneumonia because we’ll be able to see better if it’s caused by a virus.”
A large 2018 review by Dr. Linder and associates reported that 46% of antibiotics were prescribed without any infection-related diagnosis code and 20% without an office visit.
Dr. Linder routinely informs patients requesting an antibiotic about the risks of putting an ineffective chemical into their body. “I stress that it can cause rash and other allergic reactions, and even promote C diff infection,” he said. “And I also say it messes with the good bacteria in the microbiome, and they usually come around.”
Patients need to know, Dr. Linder added, that the normal course of healing the respiratory tract after acute bronchitis takes weeks. While a wet cough with sputum or phlegm will last a few days, it’s replaced with a dry annoying cough that persists for up to 3 weeks. “As long as they’re feeling generally better, that cough is normal,” he said. “A virus has run roughshod over their airways and they need a long time to heal and the cough is part of the healing process. Think how long it takes to heal a cut on a finger.”
In an era of escalating antimicrobial resistance fueled by antibiotic overuse, it’s become increasingly important to reserve antibiotics for necessary cases. According to a recent World Health Organization call to action, “Uncontrolled antimicrobial resistance is expected to lower life expectancy and lead to unprecedented health expenditure and economic losses.”
That said, there is important clinical work to be done to determine if there is a limited role for antibiotics in patients with cough, perhaps based on age and baseline severity. “Serious cough symptoms and how to treat them properly needs to be studied more, perhaps in a randomized clinical trial as this study was observational and there haven’t been any randomized trials looking at this issue since about 2012,” Dr. Merenstein said.
This research was funded by the Agency for Healthcare Research and Quality. The authors have no conflicts of interest to declare. Dr. Linder reported stock ownership in pharmaceutical companies but none that make antibiotics or other infectious disease drugs.
FROM JOURNAL OF GENERAL INTERNAL MEDICINE
Are E-Cigarettes Bad for the Heart?
E-cigarettes entered the market as consumer products without comprehensive toxicological testing,based on the assessment that they were 95% less harmful than traditional cigarettes. Further, consumer dvertising suggests that e-cigarettes are a good alternative to conventional combustible cigarettes and can serve as a gateway to quitting smoking.
However, hen considering damage to the endothelium and toxicity, e-cigarettes have a negative impact like that of conventional cigarettes. Moreover, switching to e-cigarettes often leads to dual use, said Stefan Andreas, MD, director of the Lungenfachklinik in Immenhausen, Germany, at the Congress of the German Respiratory Society and Intensive Care Medicine.
Subclinical Atherosclerosis
Because e-cigarettes have emerged relatively recently, long-term studies on their cardiac consequences are not yet available. Dr. Andreas explained that the impact on endothelial function is relevant for risk assessment. Endothelial function is a biomarker for early, subclinical atherosclerosis. “If endothelial function is impaired, the risk for heart attack and stroke is significantly increased 5-10 years later,” said Dr. Andreas.
The results of a crossover study showed reduced vascular elasticity after consuming both tobacco cigarettes and e-cigarettes. The study included 20 smokers, and endothelial function was measured using flow-mediated vasodilation.
Significant effects on the vessels were also found in a study of 31 participants who had never smoked. The study participants inhaled a nicotine-free aerosol from e-cigarettes. Before and after, parameters of endothelial function were examined using a 3.0-T MRI. After aerosol inhalation, the resistance index was 2.3% higher (P < .05), and flow-mediated vascular dilation was reduced by 34% (P < .001).
A recent review involving 372 participants from China showed that e-cigarettes lead to an increase in pulse wave velocity, with a difference of 3.08 (P < .001). “Pulse wave velocity is also a marker of endothelial function: The stiffer the vessels, the higher the pulse wave velocity,” said Dr. Andreas. The authors of the review concluded that “e-cigarettes should not be promoted as a healthier alternative to tobacco smoking.”
No Harmless Alternative
A recent review compared the effects of tobacco smoking and e-cigarettes. Although the toxic mixture in smoke is more complex, both e-cigarettes and tobacco cigarettes “impaired endothelial function to a similar extent,” they wrote. The authors attributed this finding to oxidative stress as the central mechanism.
“There is increasing evidence that e-cigarettes are not a harmless alternative to tobacco cigarettes,” wrote Thomas Münzel, MD, professor of cardiology at the University of Mainz and his team in their 2020 review, which examined studies in humans and animals. They provided an overview of the effects of tobacco/hookah smoking and e-cigarette vaping on endothelial function. They also pointed to emerging adverse effects on the proteome, transcriptome, epigenome, microbiome, and circadian clock.
Finally, a toxicological review of e-cigarettes also found alarmingly high levels of carcinogens and toxins that could have long-term effects on other organs, including the development of neurological symptoms, lung cancer, cardiovascular diseases, and cavities.
Dr. Andreas observed that even small amounts, such as those obtained through secondhand smoking, can be harmful. In 2007, Dr. Andreas and his colleagues showed that even low exposure to tobacco smoke can lead to a significant increase in cardiovascular events.
Conflicts of Interest
Dr. Andreas recommended closely examining the studies that suggest that e-cigarettes are less risky. “It is noticeable that there is a significant difference depending on whether publications were supported by the tobacco industry or not,” he emphasized.
Danish scientists found that a conflict of interest (COI) has a strong influence on study results. “In studies without a COI, e-cigarettes are found to cause damage 95% of the time. In contrast, when there is a strong conflict of interest, the result is often ‘no harm,’” said Dr. Andreas.
This effect is quite relevant for the discussion of e-cigarettes. “If scientists make a critical statement in a position paper, there will always be someone who says, ‘No, it’s different, there are these and those publications.’ The true nature of interest-driven publications on e-cigarettes is not always easy to discern,” said Dr. Andreas.
No Gateway to Quitting
E-cigarettes are used in clinical studies for tobacco cessation. The results of a randomized study showed that significantly more smokers who were switched to e-cigarettes quit smoking, compared with controls. But there was no significant difference in complete smoking cessation between groups. Moreover, 45% of smokers who switched to e-cigarettes became dual users, compared with 11% of controls.
“Translating these results means that for one person who quits smoking by using e-cigarettes, they gain five people who use both traditional cigarettes and e-cigarettes,” explained Dr. Andreas.
In their recent review, Münzel and colleagues pointed out that the assessment that e-cigarettes could help with quitting might be wrong. Rather, it seems that “e-cigarettes have the opposite effect.” They also note that the age of initiation for e-cigarettes is generally lower than for tobacco cigarettes: Consumption often starts at age 13 or 14 years. And the consumption of e-cigarettes among children and adolescents increased by 7% from 2016 to 2023.
A meta-analysis published at the end of February also shows that e-cigarettes are about as dangerous as tobacco cigarettes. They are more dangerous than not smoking, and dual use is more dangerous than tobacco cigarettes alone. “There is a need to reassess the assumption that e-cigarette use provides substantial harm reduction across all cigarette-caused diseases, particularly accounting for dual use,” wrote the authors.
“One must always consider that e-cigarettes have only been available for a relatively short time. We can only see the cumulative toxicity in 10, 20 years when we have patients who have smoked e-cigarettes only for 20 years,” said Dr. Andreas. Ultimately, however, e-cigarettes promote dual use and, consequently, additive toxicity.
Nicotine Replacement Therapies
Quitting smoking reduces the risk of cardiovascular events and premature death by 40%, even among patients with cardiovascular disease, according to a Cochrane meta-analysis. Smoking cessation reduces the risk for cardiovascular death by 39%, the risk for major adverse cardiovascular events by 43%, the risk for heart attack by 36%, the risk for stroke by 30%, and overall mortality by 40%.
Quitting smoking is the most effective measure for risk reduction, as a meta-analysis of 20 studies in patients with coronary heart disease found. Smoking cessation was associated with a 36% risk reduction compared with 29% risk reduction for statin therapy, 23% risk reduction with beta-blockers and ACE inhibitors and 15% risk reduction with aspirin.
Dr. Andreas emphasized that nicotine replacement therapies are well-researched and safe even in cardiovascular disease, as shown by a US study that included patients who had sustained a heart attack. A group of the participants was treated with nicotine patches for 10 weeks, while the other group received a placebo. After 14 weeks, 21% of the nicotine patch group achieved abstinence vs 9% of the placebo group (P = .001). Transdermal nicotine application does not lead to a significant increase in cardiovascular events in high-risk patients.
The German “Nonsmoker Heroes” app has proven to be an effective means of behavioral therapeutic coaching. A recent study of it included 17 study centers with 661 participants. About 21% of the subjects had chronic obstructive pulmonary disease, 19% had asthma. Smoking onset occurred at age 16 years. The subjects were highly dependent: > 72% had at least moderate dependence, > 58% had high to very high dependence, and the population had an average of 3.6 quit attempts. The odds ratio for self-reported abstinence was 2.2 after 6 months. “The app is not only effective, but also can be prescribed on an extrabudgetary basis,” said Dr. Andreas.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
E-cigarettes entered the market as consumer products without comprehensive toxicological testing,based on the assessment that they were 95% less harmful than traditional cigarettes. Further, consumer dvertising suggests that e-cigarettes are a good alternative to conventional combustible cigarettes and can serve as a gateway to quitting smoking.
However, hen considering damage to the endothelium and toxicity, e-cigarettes have a negative impact like that of conventional cigarettes. Moreover, switching to e-cigarettes often leads to dual use, said Stefan Andreas, MD, director of the Lungenfachklinik in Immenhausen, Germany, at the Congress of the German Respiratory Society and Intensive Care Medicine.
Subclinical Atherosclerosis
Because e-cigarettes have emerged relatively recently, long-term studies on their cardiac consequences are not yet available. Dr. Andreas explained that the impact on endothelial function is relevant for risk assessment. Endothelial function is a biomarker for early, subclinical atherosclerosis. “If endothelial function is impaired, the risk for heart attack and stroke is significantly increased 5-10 years later,” said Dr. Andreas.
The results of a crossover study showed reduced vascular elasticity after consuming both tobacco cigarettes and e-cigarettes. The study included 20 smokers, and endothelial function was measured using flow-mediated vasodilation.
Significant effects on the vessels were also found in a study of 31 participants who had never smoked. The study participants inhaled a nicotine-free aerosol from e-cigarettes. Before and after, parameters of endothelial function were examined using a 3.0-T MRI. After aerosol inhalation, the resistance index was 2.3% higher (P < .05), and flow-mediated vascular dilation was reduced by 34% (P < .001).
A recent review involving 372 participants from China showed that e-cigarettes lead to an increase in pulse wave velocity, with a difference of 3.08 (P < .001). “Pulse wave velocity is also a marker of endothelial function: The stiffer the vessels, the higher the pulse wave velocity,” said Dr. Andreas. The authors of the review concluded that “e-cigarettes should not be promoted as a healthier alternative to tobacco smoking.”
No Harmless Alternative
A recent review compared the effects of tobacco smoking and e-cigarettes. Although the toxic mixture in smoke is more complex, both e-cigarettes and tobacco cigarettes “impaired endothelial function to a similar extent,” they wrote. The authors attributed this finding to oxidative stress as the central mechanism.
“There is increasing evidence that e-cigarettes are not a harmless alternative to tobacco cigarettes,” wrote Thomas Münzel, MD, professor of cardiology at the University of Mainz and his team in their 2020 review, which examined studies in humans and animals. They provided an overview of the effects of tobacco/hookah smoking and e-cigarette vaping on endothelial function. They also pointed to emerging adverse effects on the proteome, transcriptome, epigenome, microbiome, and circadian clock.
Finally, a toxicological review of e-cigarettes also found alarmingly high levels of carcinogens and toxins that could have long-term effects on other organs, including the development of neurological symptoms, lung cancer, cardiovascular diseases, and cavities.
Dr. Andreas observed that even small amounts, such as those obtained through secondhand smoking, can be harmful. In 2007, Dr. Andreas and his colleagues showed that even low exposure to tobacco smoke can lead to a significant increase in cardiovascular events.
Conflicts of Interest
Dr. Andreas recommended closely examining the studies that suggest that e-cigarettes are less risky. “It is noticeable that there is a significant difference depending on whether publications were supported by the tobacco industry or not,” he emphasized.
Danish scientists found that a conflict of interest (COI) has a strong influence on study results. “In studies without a COI, e-cigarettes are found to cause damage 95% of the time. In contrast, when there is a strong conflict of interest, the result is often ‘no harm,’” said Dr. Andreas.
This effect is quite relevant for the discussion of e-cigarettes. “If scientists make a critical statement in a position paper, there will always be someone who says, ‘No, it’s different, there are these and those publications.’ The true nature of interest-driven publications on e-cigarettes is not always easy to discern,” said Dr. Andreas.
No Gateway to Quitting
E-cigarettes are used in clinical studies for tobacco cessation. The results of a randomized study showed that significantly more smokers who were switched to e-cigarettes quit smoking, compared with controls. But there was no significant difference in complete smoking cessation between groups. Moreover, 45% of smokers who switched to e-cigarettes became dual users, compared with 11% of controls.
“Translating these results means that for one person who quits smoking by using e-cigarettes, they gain five people who use both traditional cigarettes and e-cigarettes,” explained Dr. Andreas.
In their recent review, Münzel and colleagues pointed out that the assessment that e-cigarettes could help with quitting might be wrong. Rather, it seems that “e-cigarettes have the opposite effect.” They also note that the age of initiation for e-cigarettes is generally lower than for tobacco cigarettes: Consumption often starts at age 13 or 14 years. And the consumption of e-cigarettes among children and adolescents increased by 7% from 2016 to 2023.
A meta-analysis published at the end of February also shows that e-cigarettes are about as dangerous as tobacco cigarettes. They are more dangerous than not smoking, and dual use is more dangerous than tobacco cigarettes alone. “There is a need to reassess the assumption that e-cigarette use provides substantial harm reduction across all cigarette-caused diseases, particularly accounting for dual use,” wrote the authors.
“One must always consider that e-cigarettes have only been available for a relatively short time. We can only see the cumulative toxicity in 10, 20 years when we have patients who have smoked e-cigarettes only for 20 years,” said Dr. Andreas. Ultimately, however, e-cigarettes promote dual use and, consequently, additive toxicity.
Nicotine Replacement Therapies
Quitting smoking reduces the risk of cardiovascular events and premature death by 40%, even among patients with cardiovascular disease, according to a Cochrane meta-analysis. Smoking cessation reduces the risk for cardiovascular death by 39%, the risk for major adverse cardiovascular events by 43%, the risk for heart attack by 36%, the risk for stroke by 30%, and overall mortality by 40%.
Quitting smoking is the most effective measure for risk reduction, as a meta-analysis of 20 studies in patients with coronary heart disease found. Smoking cessation was associated with a 36% risk reduction compared with 29% risk reduction for statin therapy, 23% risk reduction with beta-blockers and ACE inhibitors and 15% risk reduction with aspirin.
Dr. Andreas emphasized that nicotine replacement therapies are well-researched and safe even in cardiovascular disease, as shown by a US study that included patients who had sustained a heart attack. A group of the participants was treated with nicotine patches for 10 weeks, while the other group received a placebo. After 14 weeks, 21% of the nicotine patch group achieved abstinence vs 9% of the placebo group (P = .001). Transdermal nicotine application does not lead to a significant increase in cardiovascular events in high-risk patients.
The German “Nonsmoker Heroes” app has proven to be an effective means of behavioral therapeutic coaching. A recent study of it included 17 study centers with 661 participants. About 21% of the subjects had chronic obstructive pulmonary disease, 19% had asthma. Smoking onset occurred at age 16 years. The subjects were highly dependent: > 72% had at least moderate dependence, > 58% had high to very high dependence, and the population had an average of 3.6 quit attempts. The odds ratio for self-reported abstinence was 2.2 after 6 months. “The app is not only effective, but also can be prescribed on an extrabudgetary basis,” said Dr. Andreas.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
E-cigarettes entered the market as consumer products without comprehensive toxicological testing,based on the assessment that they were 95% less harmful than traditional cigarettes. Further, consumer dvertising suggests that e-cigarettes are a good alternative to conventional combustible cigarettes and can serve as a gateway to quitting smoking.
However, hen considering damage to the endothelium and toxicity, e-cigarettes have a negative impact like that of conventional cigarettes. Moreover, switching to e-cigarettes often leads to dual use, said Stefan Andreas, MD, director of the Lungenfachklinik in Immenhausen, Germany, at the Congress of the German Respiratory Society and Intensive Care Medicine.
Subclinical Atherosclerosis
Because e-cigarettes have emerged relatively recently, long-term studies on their cardiac consequences are not yet available. Dr. Andreas explained that the impact on endothelial function is relevant for risk assessment. Endothelial function is a biomarker for early, subclinical atherosclerosis. “If endothelial function is impaired, the risk for heart attack and stroke is significantly increased 5-10 years later,” said Dr. Andreas.
The results of a crossover study showed reduced vascular elasticity after consuming both tobacco cigarettes and e-cigarettes. The study included 20 smokers, and endothelial function was measured using flow-mediated vasodilation.
Significant effects on the vessels were also found in a study of 31 participants who had never smoked. The study participants inhaled a nicotine-free aerosol from e-cigarettes. Before and after, parameters of endothelial function were examined using a 3.0-T MRI. After aerosol inhalation, the resistance index was 2.3% higher (P < .05), and flow-mediated vascular dilation was reduced by 34% (P < .001).
A recent review involving 372 participants from China showed that e-cigarettes lead to an increase in pulse wave velocity, with a difference of 3.08 (P < .001). “Pulse wave velocity is also a marker of endothelial function: The stiffer the vessels, the higher the pulse wave velocity,” said Dr. Andreas. The authors of the review concluded that “e-cigarettes should not be promoted as a healthier alternative to tobacco smoking.”
No Harmless Alternative
A recent review compared the effects of tobacco smoking and e-cigarettes. Although the toxic mixture in smoke is more complex, both e-cigarettes and tobacco cigarettes “impaired endothelial function to a similar extent,” they wrote. The authors attributed this finding to oxidative stress as the central mechanism.
“There is increasing evidence that e-cigarettes are not a harmless alternative to tobacco cigarettes,” wrote Thomas Münzel, MD, professor of cardiology at the University of Mainz and his team in their 2020 review, which examined studies in humans and animals. They provided an overview of the effects of tobacco/hookah smoking and e-cigarette vaping on endothelial function. They also pointed to emerging adverse effects on the proteome, transcriptome, epigenome, microbiome, and circadian clock.
Finally, a toxicological review of e-cigarettes also found alarmingly high levels of carcinogens and toxins that could have long-term effects on other organs, including the development of neurological symptoms, lung cancer, cardiovascular diseases, and cavities.
Dr. Andreas observed that even small amounts, such as those obtained through secondhand smoking, can be harmful. In 2007, Dr. Andreas and his colleagues showed that even low exposure to tobacco smoke can lead to a significant increase in cardiovascular events.
Conflicts of Interest
Dr. Andreas recommended closely examining the studies that suggest that e-cigarettes are less risky. “It is noticeable that there is a significant difference depending on whether publications were supported by the tobacco industry or not,” he emphasized.
Danish scientists found that a conflict of interest (COI) has a strong influence on study results. “In studies without a COI, e-cigarettes are found to cause damage 95% of the time. In contrast, when there is a strong conflict of interest, the result is often ‘no harm,’” said Dr. Andreas.
This effect is quite relevant for the discussion of e-cigarettes. “If scientists make a critical statement in a position paper, there will always be someone who says, ‘No, it’s different, there are these and those publications.’ The true nature of interest-driven publications on e-cigarettes is not always easy to discern,” said Dr. Andreas.
No Gateway to Quitting
E-cigarettes are used in clinical studies for tobacco cessation. The results of a randomized study showed that significantly more smokers who were switched to e-cigarettes quit smoking, compared with controls. But there was no significant difference in complete smoking cessation between groups. Moreover, 45% of smokers who switched to e-cigarettes became dual users, compared with 11% of controls.
“Translating these results means that for one person who quits smoking by using e-cigarettes, they gain five people who use both traditional cigarettes and e-cigarettes,” explained Dr. Andreas.
In their recent review, Münzel and colleagues pointed out that the assessment that e-cigarettes could help with quitting might be wrong. Rather, it seems that “e-cigarettes have the opposite effect.” They also note that the age of initiation for e-cigarettes is generally lower than for tobacco cigarettes: Consumption often starts at age 13 or 14 years. And the consumption of e-cigarettes among children and adolescents increased by 7% from 2016 to 2023.
A meta-analysis published at the end of February also shows that e-cigarettes are about as dangerous as tobacco cigarettes. They are more dangerous than not smoking, and dual use is more dangerous than tobacco cigarettes alone. “There is a need to reassess the assumption that e-cigarette use provides substantial harm reduction across all cigarette-caused diseases, particularly accounting for dual use,” wrote the authors.
“One must always consider that e-cigarettes have only been available for a relatively short time. We can only see the cumulative toxicity in 10, 20 years when we have patients who have smoked e-cigarettes only for 20 years,” said Dr. Andreas. Ultimately, however, e-cigarettes promote dual use and, consequently, additive toxicity.
Nicotine Replacement Therapies
Quitting smoking reduces the risk of cardiovascular events and premature death by 40%, even among patients with cardiovascular disease, according to a Cochrane meta-analysis. Smoking cessation reduces the risk for cardiovascular death by 39%, the risk for major adverse cardiovascular events by 43%, the risk for heart attack by 36%, the risk for stroke by 30%, and overall mortality by 40%.
Quitting smoking is the most effective measure for risk reduction, as a meta-analysis of 20 studies in patients with coronary heart disease found. Smoking cessation was associated with a 36% risk reduction compared with 29% risk reduction for statin therapy, 23% risk reduction with beta-blockers and ACE inhibitors and 15% risk reduction with aspirin.
Dr. Andreas emphasized that nicotine replacement therapies are well-researched and safe even in cardiovascular disease, as shown by a US study that included patients who had sustained a heart attack. A group of the participants was treated with nicotine patches for 10 weeks, while the other group received a placebo. After 14 weeks, 21% of the nicotine patch group achieved abstinence vs 9% of the placebo group (P = .001). Transdermal nicotine application does not lead to a significant increase in cardiovascular events in high-risk patients.
The German “Nonsmoker Heroes” app has proven to be an effective means of behavioral therapeutic coaching. A recent study of it included 17 study centers with 661 participants. About 21% of the subjects had chronic obstructive pulmonary disease, 19% had asthma. Smoking onset occurred at age 16 years. The subjects were highly dependent: > 72% had at least moderate dependence, > 58% had high to very high dependence, and the population had an average of 3.6 quit attempts. The odds ratio for self-reported abstinence was 2.2 after 6 months. “The app is not only effective, but also can be prescribed on an extrabudgetary basis,” said Dr. Andreas.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
High Infection Risk in Rheumatoid Arthritis–Associated Interstitial Lung Disease
TOPLINE:
METHODOLOGY:
- Patients with RA who have extra-articular manifestations such as ILD are highly susceptible to infections, but information on the types of infections, risk factors, and associations of infections with hospitalization and mortality is limited.
- This prospective multicenter cohort study evaluated infections in a cohort of 148 patients with RA-ILD (average age, 70 years; 57% women) recruited from 11 university hospitals in Spain between March 2015 and March 2023.
- Joint, lung, and any infection-related variables were evaluated using clinical and laboratory evaluations at baseline and selected time points till the end of the follow-up period (mean, 56.7 months).
- Researchers also investigated the common infectious sites, the etiology of the infection, vaccination status, variables associated with lung function, and clinical-therapeutic variables associated with RA.
TAKEAWAY:
- During the follow-up period, almost all (96%) patients had at least one infection, with the median time to first infection being 21.2 months and 65% of the deaths being directly related to infections.
- Respiratory infections were the most common first infections (74%) and led to death in 80% of the patients. Urinary tract (9.9%) and skin and soft tissue (9.1%) infections were the second and third most common first infections, respectively.
- Most infections were caused by SARS-CoV-2 (33.5%), Streptococcus pneumoniae (11.9%), Escherichia coli (11.9%), and Pseudomonas aeruginosa (11.1%), with mortality at 25.8% for SARS-CoV-2, 12.9% for P aeruginosa (12.9%), and 9.6% for pneumococci (9.6%).
- Increased age, disease activity, and the use of corticosteroids were associated with an elevated risk for infection and mortality in patients with RA-ILD.
IN PRACTICE:
“Our results demonstrate a high occurrence of serious infections among these patients, occurring early, recurring frequently, and proving fatal in 65% of cases,” the authors wrote.
SOURCE:
This study was led by Natalia Mena-Vázquez, MD, PhD, from Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain, and published online March 27 in Frontiers in Immunology.
LIMITATIONS:
The findings of this study have been affected by the COVID-19 pandemic. The lack of a control group also limited the ability of this study to establish any causal relationships between ILD and the clinical outcomes analyzed.
DISCLOSURE:
This study was supported by Redes de Investigación Cooperativa Orientadas a Resultados en Salud and Fundación Andaluza de Reumatología. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Patients with RA who have extra-articular manifestations such as ILD are highly susceptible to infections, but information on the types of infections, risk factors, and associations of infections with hospitalization and mortality is limited.
- This prospective multicenter cohort study evaluated infections in a cohort of 148 patients with RA-ILD (average age, 70 years; 57% women) recruited from 11 university hospitals in Spain between March 2015 and March 2023.
- Joint, lung, and any infection-related variables were evaluated using clinical and laboratory evaluations at baseline and selected time points till the end of the follow-up period (mean, 56.7 months).
- Researchers also investigated the common infectious sites, the etiology of the infection, vaccination status, variables associated with lung function, and clinical-therapeutic variables associated with RA.
TAKEAWAY:
- During the follow-up period, almost all (96%) patients had at least one infection, with the median time to first infection being 21.2 months and 65% of the deaths being directly related to infections.
- Respiratory infections were the most common first infections (74%) and led to death in 80% of the patients. Urinary tract (9.9%) and skin and soft tissue (9.1%) infections were the second and third most common first infections, respectively.
- Most infections were caused by SARS-CoV-2 (33.5%), Streptococcus pneumoniae (11.9%), Escherichia coli (11.9%), and Pseudomonas aeruginosa (11.1%), with mortality at 25.8% for SARS-CoV-2, 12.9% for P aeruginosa (12.9%), and 9.6% for pneumococci (9.6%).
- Increased age, disease activity, and the use of corticosteroids were associated with an elevated risk for infection and mortality in patients with RA-ILD.
IN PRACTICE:
“Our results demonstrate a high occurrence of serious infections among these patients, occurring early, recurring frequently, and proving fatal in 65% of cases,” the authors wrote.
SOURCE:
This study was led by Natalia Mena-Vázquez, MD, PhD, from Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain, and published online March 27 in Frontiers in Immunology.
LIMITATIONS:
The findings of this study have been affected by the COVID-19 pandemic. The lack of a control group also limited the ability of this study to establish any causal relationships between ILD and the clinical outcomes analyzed.
DISCLOSURE:
This study was supported by Redes de Investigación Cooperativa Orientadas a Resultados en Salud and Fundación Andaluza de Reumatología. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Patients with RA who have extra-articular manifestations such as ILD are highly susceptible to infections, but information on the types of infections, risk factors, and associations of infections with hospitalization and mortality is limited.
- This prospective multicenter cohort study evaluated infections in a cohort of 148 patients with RA-ILD (average age, 70 years; 57% women) recruited from 11 university hospitals in Spain between March 2015 and March 2023.
- Joint, lung, and any infection-related variables were evaluated using clinical and laboratory evaluations at baseline and selected time points till the end of the follow-up period (mean, 56.7 months).
- Researchers also investigated the common infectious sites, the etiology of the infection, vaccination status, variables associated with lung function, and clinical-therapeutic variables associated with RA.
TAKEAWAY:
- During the follow-up period, almost all (96%) patients had at least one infection, with the median time to first infection being 21.2 months and 65% of the deaths being directly related to infections.
- Respiratory infections were the most common first infections (74%) and led to death in 80% of the patients. Urinary tract (9.9%) and skin and soft tissue (9.1%) infections were the second and third most common first infections, respectively.
- Most infections were caused by SARS-CoV-2 (33.5%), Streptococcus pneumoniae (11.9%), Escherichia coli (11.9%), and Pseudomonas aeruginosa (11.1%), with mortality at 25.8% for SARS-CoV-2, 12.9% for P aeruginosa (12.9%), and 9.6% for pneumococci (9.6%).
- Increased age, disease activity, and the use of corticosteroids were associated with an elevated risk for infection and mortality in patients with RA-ILD.
IN PRACTICE:
“Our results demonstrate a high occurrence of serious infections among these patients, occurring early, recurring frequently, and proving fatal in 65% of cases,” the authors wrote.
SOURCE:
This study was led by Natalia Mena-Vázquez, MD, PhD, from Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain, and published online March 27 in Frontiers in Immunology.
LIMITATIONS:
The findings of this study have been affected by the COVID-19 pandemic. The lack of a control group also limited the ability of this study to establish any causal relationships between ILD and the clinical outcomes analyzed.
DISCLOSURE:
This study was supported by Redes de Investigación Cooperativa Orientadas a Resultados en Salud and Fundación Andaluza de Reumatología. The authors declared having no conflicts of interest.
A version of this article appeared on Medscape.com.