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COPD patients with high plasma immunoglobulin E are more likely to have exacerbations and die from any cause, based on a Danish population-cohort study.
hinting at different subsets of patients with COPD, lead author Yunus Çolak MD, PhD, of Copenhagen University Hospital, and colleagues reported.
“Additional biomarkers are necessary as blood eosinophils alone seem insufficient for risk stratification in COPD,” the investigators wrote in Annals of Allergy, Asthma & Immunology. “Since asthma and COPD share some pathophysiological mechanisms, a logical approach would be to investigate well-known biomarkers for asthma in COPD and vice versa.”
Dr. Çolak and colleagues cited previous research supporting this perspective. Specifically, IgE-targeting monoclonal antibodies have shown promise in patients with severe asthma and asthma-COPD overlap, whereas COPD with high IgE has been associated with a history of lung function decline and previous exacerbations.
The present study drew from a database of 46,598 adults enrolled in the Copenhagen General Population study. All participants underwent physical examination, completed a questionnaire, and provided blood for analysis. From this population, 1,559 individuals had COPD, among whom 446 had high plasma IgE (at least 76 IU/mL).
Over a median follow-up of 6.9 years in the COPD group, 224 severe exacerbations and 434 deaths of any cause occurred. Compared with COPD patients who had normal plasma IgE, those with high IgE were 43% more likely to have severe exacerbation (hazard ratio, 1.43; 95% confidence interval, 1.07-1.89) and 30% more likely to die of any cause (HR, 1.30; 95% CI, 1.06-1.62). These risks were similar when excluding patients with IgE of 700 IU/mL or higher.
“These findings suggest that plasma IgE concentration may be a potential prognostic biomarker and treatment target for a subset of COPD patient,” wrote Dr. Çolak and colleagues.
The above risks increased moderately when the high IgE group was trimmed to include only those with low eosinophils (less than 300 cells/mcL); in this subgroup, risk of exacerbation was increased 62% (HR, 1.62; 95% CI, 1.17-2.24), while risk of all-cause mortality was increased 47% (HR, 1.47; 95% CI, 1.14-1.88).
“We were not able to show that individuals with higher blood eosinophils further stratified by IgE had higher risk of severe exacerbation or all-cause mortality,” the investigators wrote, although they noted “the relatively low statistical power in stratified analysis,” considering the wide confidence intervals observed.
“Thus, we should be careful with interpreting the results in relation to blood eosinophils and IgE combined,” they suggested. “However, we believe that the mechanisms driving exacerbations through plasma IgE are different from those driving blood eosinophils, and we believe that plasma IgE may be a marker for a subset of COPD patients similar to blood eosinophils, which is compatible with the heterogeneity of patients with COPD.”
According to principal author Shoaib Afzal, MD, PhD, of Copenhagen University Hospital, the findings are “probably no surprise for practitioners that often observe overlap between asthma and COPD pathology.”
As smoking prevalence goes down in many countries, relatively more never-smokers are being diagnosed with COPD, Dr. Afzal said in a written comment, “which means that asthma as a risk factor for COPD is gaining importance.”
While patients with asthma can be treated with IgE-targeting omalizumab, a trial evaluating the same biologic for COPD patients with high IgE was withdrawn because of a lack of recruitment; however, Dr. Afzal suggested that this should not be the end of the story, since these new data imply that more patients could benefit than previously recognized.
“Our observational study has generated a hypothesis that needs to be tested by pulmonologists in randomized interventions trials designed with updated inclusion criteria,” he said.
Such trials are needed, Dr. Afzal went on, because they could help unlock the “huge” potential benefit that may come from characterizing COPD patients beyond “exposures, symptoms, and spirometry.”
“Sadly, the progress in establishing biomarkers in COPD for improving risk stratification and treatment allocation have been rather disappointing in the last decades, with the exception of small successes with eosinophils and perhaps FeNO,” Dr. Afzal said.
Nathaniel Marchetti, DO, professor of thoracic medicine and surgery at Temple University and medical director of the respiratory ICU at Temple University Hospital, both in Philadelphia, said the study by Dr. Afzal and colleagues is noteworthy because “biomarkers for COPD are desperately needed to help risk stratify patients for exacerbation risk and risk of disease progression and even mortality.”
In a written comment, Dr. Marchetti agreed with Dr. Afzal that the findings “open the possibility for interventional trials targeting IgE,” which could one day reshape the way patients with COPD are treated.
“I think that biomarkers will become vital in caring for patients with COPD in the future,” Dr. Marchetti said. “There will be medications that will be used to target different pathways of inflammation that drive disease progression and exacerbations. Biomarkers will be important in driving personalized medicine in COPD. We already know the disease seems to vary greatly from patient to patient.”
The study was supported by The Capital Region of Copenhagen, The Danish Lung Foundation, The Velux Foundation, and others. The investigators disclosed relationships with Boehringer Ingelheim, AstraZeneca, Sanofi Genzyme, and others. Dr. Marchetti disclosed no conflicts of interest.
COPD patients with high plasma immunoglobulin E are more likely to have exacerbations and die from any cause, based on a Danish population-cohort study.
hinting at different subsets of patients with COPD, lead author Yunus Çolak MD, PhD, of Copenhagen University Hospital, and colleagues reported.
“Additional biomarkers are necessary as blood eosinophils alone seem insufficient for risk stratification in COPD,” the investigators wrote in Annals of Allergy, Asthma & Immunology. “Since asthma and COPD share some pathophysiological mechanisms, a logical approach would be to investigate well-known biomarkers for asthma in COPD and vice versa.”
Dr. Çolak and colleagues cited previous research supporting this perspective. Specifically, IgE-targeting monoclonal antibodies have shown promise in patients with severe asthma and asthma-COPD overlap, whereas COPD with high IgE has been associated with a history of lung function decline and previous exacerbations.
The present study drew from a database of 46,598 adults enrolled in the Copenhagen General Population study. All participants underwent physical examination, completed a questionnaire, and provided blood for analysis. From this population, 1,559 individuals had COPD, among whom 446 had high plasma IgE (at least 76 IU/mL).
Over a median follow-up of 6.9 years in the COPD group, 224 severe exacerbations and 434 deaths of any cause occurred. Compared with COPD patients who had normal plasma IgE, those with high IgE were 43% more likely to have severe exacerbation (hazard ratio, 1.43; 95% confidence interval, 1.07-1.89) and 30% more likely to die of any cause (HR, 1.30; 95% CI, 1.06-1.62). These risks were similar when excluding patients with IgE of 700 IU/mL or higher.
“These findings suggest that plasma IgE concentration may be a potential prognostic biomarker and treatment target for a subset of COPD patient,” wrote Dr. Çolak and colleagues.
The above risks increased moderately when the high IgE group was trimmed to include only those with low eosinophils (less than 300 cells/mcL); in this subgroup, risk of exacerbation was increased 62% (HR, 1.62; 95% CI, 1.17-2.24), while risk of all-cause mortality was increased 47% (HR, 1.47; 95% CI, 1.14-1.88).
“We were not able to show that individuals with higher blood eosinophils further stratified by IgE had higher risk of severe exacerbation or all-cause mortality,” the investigators wrote, although they noted “the relatively low statistical power in stratified analysis,” considering the wide confidence intervals observed.
“Thus, we should be careful with interpreting the results in relation to blood eosinophils and IgE combined,” they suggested. “However, we believe that the mechanisms driving exacerbations through plasma IgE are different from those driving blood eosinophils, and we believe that plasma IgE may be a marker for a subset of COPD patients similar to blood eosinophils, which is compatible with the heterogeneity of patients with COPD.”
According to principal author Shoaib Afzal, MD, PhD, of Copenhagen University Hospital, the findings are “probably no surprise for practitioners that often observe overlap between asthma and COPD pathology.”
As smoking prevalence goes down in many countries, relatively more never-smokers are being diagnosed with COPD, Dr. Afzal said in a written comment, “which means that asthma as a risk factor for COPD is gaining importance.”
While patients with asthma can be treated with IgE-targeting omalizumab, a trial evaluating the same biologic for COPD patients with high IgE was withdrawn because of a lack of recruitment; however, Dr. Afzal suggested that this should not be the end of the story, since these new data imply that more patients could benefit than previously recognized.
“Our observational study has generated a hypothesis that needs to be tested by pulmonologists in randomized interventions trials designed with updated inclusion criteria,” he said.
Such trials are needed, Dr. Afzal went on, because they could help unlock the “huge” potential benefit that may come from characterizing COPD patients beyond “exposures, symptoms, and spirometry.”
“Sadly, the progress in establishing biomarkers in COPD for improving risk stratification and treatment allocation have been rather disappointing in the last decades, with the exception of small successes with eosinophils and perhaps FeNO,” Dr. Afzal said.
Nathaniel Marchetti, DO, professor of thoracic medicine and surgery at Temple University and medical director of the respiratory ICU at Temple University Hospital, both in Philadelphia, said the study by Dr. Afzal and colleagues is noteworthy because “biomarkers for COPD are desperately needed to help risk stratify patients for exacerbation risk and risk of disease progression and even mortality.”
In a written comment, Dr. Marchetti agreed with Dr. Afzal that the findings “open the possibility for interventional trials targeting IgE,” which could one day reshape the way patients with COPD are treated.
“I think that biomarkers will become vital in caring for patients with COPD in the future,” Dr. Marchetti said. “There will be medications that will be used to target different pathways of inflammation that drive disease progression and exacerbations. Biomarkers will be important in driving personalized medicine in COPD. We already know the disease seems to vary greatly from patient to patient.”
The study was supported by The Capital Region of Copenhagen, The Danish Lung Foundation, The Velux Foundation, and others. The investigators disclosed relationships with Boehringer Ingelheim, AstraZeneca, Sanofi Genzyme, and others. Dr. Marchetti disclosed no conflicts of interest.
COPD patients with high plasma immunoglobulin E are more likely to have exacerbations and die from any cause, based on a Danish population-cohort study.
hinting at different subsets of patients with COPD, lead author Yunus Çolak MD, PhD, of Copenhagen University Hospital, and colleagues reported.
“Additional biomarkers are necessary as blood eosinophils alone seem insufficient for risk stratification in COPD,” the investigators wrote in Annals of Allergy, Asthma & Immunology. “Since asthma and COPD share some pathophysiological mechanisms, a logical approach would be to investigate well-known biomarkers for asthma in COPD and vice versa.”
Dr. Çolak and colleagues cited previous research supporting this perspective. Specifically, IgE-targeting monoclonal antibodies have shown promise in patients with severe asthma and asthma-COPD overlap, whereas COPD with high IgE has been associated with a history of lung function decline and previous exacerbations.
The present study drew from a database of 46,598 adults enrolled in the Copenhagen General Population study. All participants underwent physical examination, completed a questionnaire, and provided blood for analysis. From this population, 1,559 individuals had COPD, among whom 446 had high plasma IgE (at least 76 IU/mL).
Over a median follow-up of 6.9 years in the COPD group, 224 severe exacerbations and 434 deaths of any cause occurred. Compared with COPD patients who had normal plasma IgE, those with high IgE were 43% more likely to have severe exacerbation (hazard ratio, 1.43; 95% confidence interval, 1.07-1.89) and 30% more likely to die of any cause (HR, 1.30; 95% CI, 1.06-1.62). These risks were similar when excluding patients with IgE of 700 IU/mL or higher.
“These findings suggest that plasma IgE concentration may be a potential prognostic biomarker and treatment target for a subset of COPD patient,” wrote Dr. Çolak and colleagues.
The above risks increased moderately when the high IgE group was trimmed to include only those with low eosinophils (less than 300 cells/mcL); in this subgroup, risk of exacerbation was increased 62% (HR, 1.62; 95% CI, 1.17-2.24), while risk of all-cause mortality was increased 47% (HR, 1.47; 95% CI, 1.14-1.88).
“We were not able to show that individuals with higher blood eosinophils further stratified by IgE had higher risk of severe exacerbation or all-cause mortality,” the investigators wrote, although they noted “the relatively low statistical power in stratified analysis,” considering the wide confidence intervals observed.
“Thus, we should be careful with interpreting the results in relation to blood eosinophils and IgE combined,” they suggested. “However, we believe that the mechanisms driving exacerbations through plasma IgE are different from those driving blood eosinophils, and we believe that plasma IgE may be a marker for a subset of COPD patients similar to blood eosinophils, which is compatible with the heterogeneity of patients with COPD.”
According to principal author Shoaib Afzal, MD, PhD, of Copenhagen University Hospital, the findings are “probably no surprise for practitioners that often observe overlap between asthma and COPD pathology.”
As smoking prevalence goes down in many countries, relatively more never-smokers are being diagnosed with COPD, Dr. Afzal said in a written comment, “which means that asthma as a risk factor for COPD is gaining importance.”
While patients with asthma can be treated with IgE-targeting omalizumab, a trial evaluating the same biologic for COPD patients with high IgE was withdrawn because of a lack of recruitment; however, Dr. Afzal suggested that this should not be the end of the story, since these new data imply that more patients could benefit than previously recognized.
“Our observational study has generated a hypothesis that needs to be tested by pulmonologists in randomized interventions trials designed with updated inclusion criteria,” he said.
Such trials are needed, Dr. Afzal went on, because they could help unlock the “huge” potential benefit that may come from characterizing COPD patients beyond “exposures, symptoms, and spirometry.”
“Sadly, the progress in establishing biomarkers in COPD for improving risk stratification and treatment allocation have been rather disappointing in the last decades, with the exception of small successes with eosinophils and perhaps FeNO,” Dr. Afzal said.
Nathaniel Marchetti, DO, professor of thoracic medicine and surgery at Temple University and medical director of the respiratory ICU at Temple University Hospital, both in Philadelphia, said the study by Dr. Afzal and colleagues is noteworthy because “biomarkers for COPD are desperately needed to help risk stratify patients for exacerbation risk and risk of disease progression and even mortality.”
In a written comment, Dr. Marchetti agreed with Dr. Afzal that the findings “open the possibility for interventional trials targeting IgE,” which could one day reshape the way patients with COPD are treated.
“I think that biomarkers will become vital in caring for patients with COPD in the future,” Dr. Marchetti said. “There will be medications that will be used to target different pathways of inflammation that drive disease progression and exacerbations. Biomarkers will be important in driving personalized medicine in COPD. We already know the disease seems to vary greatly from patient to patient.”
The study was supported by The Capital Region of Copenhagen, The Danish Lung Foundation, The Velux Foundation, and others. The investigators disclosed relationships with Boehringer Ingelheim, AstraZeneca, Sanofi Genzyme, and others. Dr. Marchetti disclosed no conflicts of interest.
FROM ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY