COPD

Patients with chronic obstructive pulmonary disease who received opioids or benzodiazepines had a greater risk of hospitalization for respiratory-related adverse events, according to recent research from Annals of the American Thoracic Society.

sdominick/Getty Images

In addition, the risk of hospitalization because of respiratory events for patients with chronic obstructive pulmonary disease (COPD) was greater when opioid and benzodiazepine medications were combined, compared with patients who did not take either medication, Jacques G. Baillargeon, PhD, of the department of preventive medicine and community health at the University of Texas, Galveston, and colleagues wrote.

“Patients with COPD and their physicians should judiciously assess the risks and benefits of opioids and benzodiazepines, alone and in combination, and preferentially recommend nonopioid and nonbenzodiazepine approaches for pain, sleep, and anxiety management in patients with COPD,” the investigators wrote.

The researchers performed a case-control study of 3,232 Medicare beneficiary cases of COPD patients who were aged at least 66 years. Patients were included if they experienced a hospitalization related to a COPD-related adverse event with a respiratory diagnosis in 2014 and then matched to one or two control patients (total, 6,247 patients) based on age at hospitalization, gender, COPD medication, COPD complexity, obstructive sleep apnea, and socioeconomic status. COPD complexity was assigned to three levels (low, moderate, high) and calculated using the patient’s comorbid respiratory conditions and associated medical procedures in the 12 months prior to their hospitalization.

They found that, in the 30 days before COPD-related hospitalization, use of opioids was associated with greater likelihood of hospitalization (adjusted odds ratio, 1.73; 95% confidence interval, 1.52-1.97), as was use of benzodiazepines (aOR, 1.42; 95% CI, 1.21-1.66). When patients used both opioids and benzodiazepines, they had a significantly higher risk of hospitalization, compared with patients who did not use opioids or benzodiazepines (aOR, 2.32; 95% CI, 1.94-2.77).

In the 60 days prior to hospitalization, there was also a greater likelihood of hospitalization among COPD patients who used opioids (aOR, 1.66; 95% CI, 1.47-1.88), benzodiazepines (aOR, 1.44; 95% CI, 1.24-1.67), and both opioids and benzodiazepines (aOR, 2.27; 95% CI, 1.93-2.67); at 90 days, this higher risk of hospitalization persisted among COPD patients taking opioids (aOR, 1.58; 95% CI, 1.40-1.78), benzodiazepines (aOR, 1.40; 95% CI, 1.20-1.63), and both opioids and benzodiazepines (aOR, 2.21; 95% CI, 1.88-2.59).

The researchers acknowledged that one potential limitation in the study was how COPD diagnoses were obtained through coding performed by clinicians instead of from laboratory testing. Confounding by COPD indication and severity; use of over-the-counter medication or opioids and benzodiazepines received illegally; and lack of analyses of potential confounders such as diet, alcohol use, smoking status and herbal supplement use were other limitations.

This study was supported by an award from the National Center for Advancing Translational Sciences and National Institutes of Health. Dr. Baillargeon had no disclosures.

SOURCE: Baillargeon JG et al. Ann Am Thorac Soc. 2019 Oct 1. doi: 10.1513/AnnalsATS.201901-024OC.

Patients with chronic obstructive pulmonary disease who received opioids or benzodiazepines had a greater risk of hospitalization for respiratory-related adverse events, according to recent research from Annals of the American Thoracic Society.

sdominick/Getty Images

In addition, the risk of hospitalization because of respiratory events for patients with chronic obstructive pulmonary disease (COPD) was greater when opioid and benzodiazepine medications were combined, compared with patients who did not take either medication, Jacques G. Baillargeon, PhD, of the department of preventive medicine and community health at the University of Texas, Galveston, and colleagues wrote.

“Patients with COPD and their physicians should judiciously assess the risks and benefits of opioids and benzodiazepines, alone and in combination, and preferentially recommend nonopioid and nonbenzodiazepine approaches for pain, sleep, and anxiety management in patients with COPD,” the investigators wrote.

The researchers performed a case-control study of 3,232 Medicare beneficiary cases of COPD patients who were aged at least 66 years. Patients were included if they experienced a hospitalization related to a COPD-related adverse event with a respiratory diagnosis in 2014 and then matched to one or two control patients (total, 6,247 patients) based on age at hospitalization, gender, COPD medication, COPD complexity, obstructive sleep apnea, and socioeconomic status. COPD complexity was assigned to three levels (low, moderate, high) and calculated using the patient’s comorbid respiratory conditions and associated medical procedures in the 12 months prior to their hospitalization.

They found that, in the 30 days before COPD-related hospitalization, use of opioids was associated with greater likelihood of hospitalization (adjusted odds ratio, 1.73; 95% confidence interval, 1.52-1.97), as was use of benzodiazepines (aOR, 1.42; 95% CI, 1.21-1.66). When patients used both opioids and benzodiazepines, they had a significantly higher risk of hospitalization, compared with patients who did not use opioids or benzodiazepines (aOR, 2.32; 95% CI, 1.94-2.77).

In the 60 days prior to hospitalization, there was also a greater likelihood of hospitalization among COPD patients who used opioids (aOR, 1.66; 95% CI, 1.47-1.88), benzodiazepines (aOR, 1.44; 95% CI, 1.24-1.67), and both opioids and benzodiazepines (aOR, 2.27; 95% CI, 1.93-2.67); at 90 days, this higher risk of hospitalization persisted among COPD patients taking opioids (aOR, 1.58; 95% CI, 1.40-1.78), benzodiazepines (aOR, 1.40; 95% CI, 1.20-1.63), and both opioids and benzodiazepines (aOR, 2.21; 95% CI, 1.88-2.59).

The researchers acknowledged that one potential limitation in the study was how COPD diagnoses were obtained through coding performed by clinicians instead of from laboratory testing. Confounding by COPD indication and severity; use of over-the-counter medication or opioids and benzodiazepines received illegally; and lack of analyses of potential confounders such as diet, alcohol use, smoking status and herbal supplement use were other limitations.

This study was supported by an award from the National Center for Advancing Translational Sciences and National Institutes of Health. Dr. Baillargeon had no disclosures.

SOURCE: Baillargeon JG et al. Ann Am Thorac Soc. 2019 Oct 1. doi: 10.1513/AnnalsATS.201901-024OC.

Patients with chronic obstructive pulmonary disease who received opioids or benzodiazepines had a greater risk of hospitalization for respiratory-related adverse events, according to recent research from Annals of the American Thoracic Society.

sdominick/Getty Images

In addition, the risk of hospitalization because of respiratory events for patients with chronic obstructive pulmonary disease (COPD) was greater when opioid and benzodiazepine medications were combined, compared with patients who did not take either medication, Jacques G. Baillargeon, PhD, of the department of preventive medicine and community health at the University of Texas, Galveston, and colleagues wrote.

“Patients with COPD and their physicians should judiciously assess the risks and benefits of opioids and benzodiazepines, alone and in combination, and preferentially recommend nonopioid and nonbenzodiazepine approaches for pain, sleep, and anxiety management in patients with COPD,” the investigators wrote.

The researchers performed a case-control study of 3,232 Medicare beneficiary cases of COPD patients who were aged at least 66 years. Patients were included if they experienced a hospitalization related to a COPD-related adverse event with a respiratory diagnosis in 2014 and then matched to one or two control patients (total, 6,247 patients) based on age at hospitalization, gender, COPD medication, COPD complexity, obstructive sleep apnea, and socioeconomic status. COPD complexity was assigned to three levels (low, moderate, high) and calculated using the patient’s comorbid respiratory conditions and associated medical procedures in the 12 months prior to their hospitalization.

They found that, in the 30 days before COPD-related hospitalization, use of opioids was associated with greater likelihood of hospitalization (adjusted odds ratio, 1.73; 95% confidence interval, 1.52-1.97), as was use of benzodiazepines (aOR, 1.42; 95% CI, 1.21-1.66). When patients used both opioids and benzodiazepines, they had a significantly higher risk of hospitalization, compared with patients who did not use opioids or benzodiazepines (aOR, 2.32; 95% CI, 1.94-2.77).

In the 60 days prior to hospitalization, there was also a greater likelihood of hospitalization among COPD patients who used opioids (aOR, 1.66; 95% CI, 1.47-1.88), benzodiazepines (aOR, 1.44; 95% CI, 1.24-1.67), and both opioids and benzodiazepines (aOR, 2.27; 95% CI, 1.93-2.67); at 90 days, this higher risk of hospitalization persisted among COPD patients taking opioids (aOR, 1.58; 95% CI, 1.40-1.78), benzodiazepines (aOR, 1.40; 95% CI, 1.20-1.63), and both opioids and benzodiazepines (aOR, 2.21; 95% CI, 1.88-2.59).

The researchers acknowledged that one potential limitation in the study was how COPD diagnoses were obtained through coding performed by clinicians instead of from laboratory testing. Confounding by COPD indication and severity; use of over-the-counter medication or opioids and benzodiazepines received illegally; and lack of analyses of potential confounders such as diet, alcohol use, smoking status and herbal supplement use were other limitations.

This study was supported by an award from the National Center for Advancing Translational Sciences and National Institutes of Health. Dr. Baillargeon had no disclosures.

SOURCE: Baillargeon JG et al. Ann Am Thorac Soc. 2019 Oct 1. doi: 10.1513/AnnalsATS.201901-024OC.

NEW ORLEANS – A history of recent exacerbations did not significantly affect the safety or efficacy of aclidinium bromide (Tudorza) in patients with moderate to severe chronic obstructive pulmonary disease and high cardiovascular risk, analysis of a postmarketing surveillance trial suggests.

Andrew D. Bowser/MDedge News

Regardless of exacerbation history, the long-acting muscarinic antagonist reduced the rate of moderate or severe COPD exacerbations versus placebo in this subgroup analysis of the phase IV ASCENT-COPD trial, presented here at the annual meeting of the American College of Chest Physicians.

At the same time, there were no significant increases in the risk of mortality or major cardiac adverse events (MACE) for those patients who had an exacerbation in the past year versus those who did not, according to investigator Robert A. Wise, MD.

Those findings may be reassuring, given that COPD patients commonly have comorbidities and cardiovascular risk factors, according to Dr. Wise, professor of medicine at the Johns Hopkins University, Baltimore.

“There’s a concern and some evidence that patients who have a propensity to COPD exacerbations may also have an increased risk for cardiovascular events,” Dr. Wise said in a podium presentation.

Accordingly, he and coinvestigators sought to tease out the impact of COPD exacerbations on safety as well as efficacy in the randomized, placebo-controlled ASCENT-COPD trial, which included 3,630 patients with moderate to severe COPD plus a cardiovascular disease history or multiple atherothrombotic risk factors.

Of the patients who were analyzed in the study, 1,433 patients had at least one treated COPD exacerbation in the year before screening for the study, while 2,156 had no exacerbations in the prior year, Dr. Wise said.

Top-line results of that study, published several months ago, showed that aclidinium did not increase MACE risk over 3 years, and reduced the rate of moderate to severe COPD exacerbations over the first year (JAMA. 2019 7 May 7;321[17]:1693-701).

In this latest analysis, presented at the meeting, risk of MACE with aclidinium treatment was not increased versus placebo, irrespective of whether they had exacerbations in the prior year (interaction P = .233); likewise, the risk of all-cause mortality was similar between groups (P = .154).

In terms of reduction in moderate or severe COPD exacerbations in the first year, aclidinium was superior to placebo both for the patients who had at least one or exacerbation in the prior year (rate ratio, 0.80) and those who had no exacerbations in the prior year (RR, 0.69).

“This translates into a number-needed-to-treat to prevent one exacerbation of about 11 patients for those without an exacerbation, compared to about 6 patients for those with a prior exacerbation,” Dr. Wise said in his presentation.

The ASCENT-COPD study was funded initially by Forest Laboratories and later by AstraZeneca and Circassia. Dr. Wise provided disclosures related to AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Sunovion, Mylan/Theravance, Contrafect, Pearl, Merck, Verona, Novartis, AbbVie, Syneos, Regeneron, and Kiniksa.

SOURCE: Wise R et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.231.

NEW ORLEANS – A history of recent exacerbations did not significantly affect the safety or efficacy of aclidinium bromide (Tudorza) in patients with moderate to severe chronic obstructive pulmonary disease and high cardiovascular risk, analysis of a postmarketing surveillance trial suggests.

Andrew D. Bowser/MDedge News

Regardless of exacerbation history, the long-acting muscarinic antagonist reduced the rate of moderate or severe COPD exacerbations versus placebo in this subgroup analysis of the phase IV ASCENT-COPD trial, presented here at the annual meeting of the American College of Chest Physicians.

At the same time, there were no significant increases in the risk of mortality or major cardiac adverse events (MACE) for those patients who had an exacerbation in the past year versus those who did not, according to investigator Robert A. Wise, MD.

Those findings may be reassuring, given that COPD patients commonly have comorbidities and cardiovascular risk factors, according to Dr. Wise, professor of medicine at the Johns Hopkins University, Baltimore.

“There’s a concern and some evidence that patients who have a propensity to COPD exacerbations may also have an increased risk for cardiovascular events,” Dr. Wise said in a podium presentation.

Accordingly, he and coinvestigators sought to tease out the impact of COPD exacerbations on safety as well as efficacy in the randomized, placebo-controlled ASCENT-COPD trial, which included 3,630 patients with moderate to severe COPD plus a cardiovascular disease history or multiple atherothrombotic risk factors.

Of the patients who were analyzed in the study, 1,433 patients had at least one treated COPD exacerbation in the year before screening for the study, while 2,156 had no exacerbations in the prior year, Dr. Wise said.

Top-line results of that study, published several months ago, showed that aclidinium did not increase MACE risk over 3 years, and reduced the rate of moderate to severe COPD exacerbations over the first year (JAMA. 2019 7 May 7;321[17]:1693-701).

In this latest analysis, presented at the meeting, risk of MACE with aclidinium treatment was not increased versus placebo, irrespective of whether they had exacerbations in the prior year (interaction P = .233); likewise, the risk of all-cause mortality was similar between groups (P = .154).

In terms of reduction in moderate or severe COPD exacerbations in the first year, aclidinium was superior to placebo both for the patients who had at least one or exacerbation in the prior year (rate ratio, 0.80) and those who had no exacerbations in the prior year (RR, 0.69).

“This translates into a number-needed-to-treat to prevent one exacerbation of about 11 patients for those without an exacerbation, compared to about 6 patients for those with a prior exacerbation,” Dr. Wise said in his presentation.

The ASCENT-COPD study was funded initially by Forest Laboratories and later by AstraZeneca and Circassia. Dr. Wise provided disclosures related to AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Sunovion, Mylan/Theravance, Contrafect, Pearl, Merck, Verona, Novartis, AbbVie, Syneos, Regeneron, and Kiniksa.

SOURCE: Wise R et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.231.

NEW ORLEANS – A history of recent exacerbations did not significantly affect the safety or efficacy of aclidinium bromide (Tudorza) in patients with moderate to severe chronic obstructive pulmonary disease and high cardiovascular risk, analysis of a postmarketing surveillance trial suggests.

Andrew D. Bowser/MDedge News

Regardless of exacerbation history, the long-acting muscarinic antagonist reduced the rate of moderate or severe COPD exacerbations versus placebo in this subgroup analysis of the phase IV ASCENT-COPD trial, presented here at the annual meeting of the American College of Chest Physicians.

At the same time, there were no significant increases in the risk of mortality or major cardiac adverse events (MACE) for those patients who had an exacerbation in the past year versus those who did not, according to investigator Robert A. Wise, MD.

Those findings may be reassuring, given that COPD patients commonly have comorbidities and cardiovascular risk factors, according to Dr. Wise, professor of medicine at the Johns Hopkins University, Baltimore.

“There’s a concern and some evidence that patients who have a propensity to COPD exacerbations may also have an increased risk for cardiovascular events,” Dr. Wise said in a podium presentation.

Accordingly, he and coinvestigators sought to tease out the impact of COPD exacerbations on safety as well as efficacy in the randomized, placebo-controlled ASCENT-COPD trial, which included 3,630 patients with moderate to severe COPD plus a cardiovascular disease history or multiple atherothrombotic risk factors.

Of the patients who were analyzed in the study, 1,433 patients had at least one treated COPD exacerbation in the year before screening for the study, while 2,156 had no exacerbations in the prior year, Dr. Wise said.

Top-line results of that study, published several months ago, showed that aclidinium did not increase MACE risk over 3 years, and reduced the rate of moderate to severe COPD exacerbations over the first year (JAMA. 2019 7 May 7;321[17]:1693-701).

In this latest analysis, presented at the meeting, risk of MACE with aclidinium treatment was not increased versus placebo, irrespective of whether they had exacerbations in the prior year (interaction P = .233); likewise, the risk of all-cause mortality was similar between groups (P = .154).

In terms of reduction in moderate or severe COPD exacerbations in the first year, aclidinium was superior to placebo both for the patients who had at least one or exacerbation in the prior year (rate ratio, 0.80) and those who had no exacerbations in the prior year (RR, 0.69).

“This translates into a number-needed-to-treat to prevent one exacerbation of about 11 patients for those without an exacerbation, compared to about 6 patients for those with a prior exacerbation,” Dr. Wise said in his presentation.

The ASCENT-COPD study was funded initially by Forest Laboratories and later by AstraZeneca and Circassia. Dr. Wise provided disclosures related to AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Sunovion, Mylan/Theravance, Contrafect, Pearl, Merck, Verona, Novartis, AbbVie, Syneos, Regeneron, and Kiniksa.

SOURCE: Wise R et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.231.

A new study has found that beta-blocker treatment did not prevent exacerbations in patients with moderate or severe chronic obstructive pulmonary disease (COPD).

decade3d/Thinkstock

“These results differ from previously reported findings from observational studies suggesting that beta-blockers reduce the risks of exacerbation and death from any cause in patients with COPD,” wrote Mark T. Dransfield, MD, of the University of Alabama at Birmingham and coauthors. Their findings were presented at the annual meeting of the American College of Chest Physicians and also were published simultaneously in the New England Journal of Medicine.

To determine the value of beta-blockers as a potential treatment for COPD, the researchers launched a prospective randomized trial called BLOCK COPD, consisting of 532 patients with moderate or severe COPD. They were assigned to two groups: those receiving extended-release metoprolol (n = 268) and those receiving placebo (n = 264). The mean age of all patients was 65 years.

The groups saw no significant difference in median time until the first exacerbation, which was 202 days (95% confidence interval, 162-282) in the metoprolol group and 222 days (95% CI, 189-295) in the placebo group (hazard ratio, 1.05; 95% CI, 0.84-1.32; P = .66). Metoprolol was associated with a higher risk of severe or very severe exacerbations leading to hospitalization (HR, 1.91; 95% CI, 1.29-2.83). During treatment, there were 11 deaths in the metoprolol group and 5 deaths in the placebo group.

Though there was no evidence of increases in patient-reported adverse events related to metoprolol, more discontinuations did occur in the metoprolol group compared with placebo (11.2% vs. 6.1%).

The authors acknowledged their study’s limitations, chiefly including the fact that the trial was ended early “on the basis of the conditional power analyses and concern about safety.” In addition, the reduction of heart rate and blood pressure in the metoprolol group made it impossible to fully blind the study. Finally, many patients in the trial had already suffered the effects of moderate to severe COPD, including previous hospitalization and the need for supplemental oxygen, leading to uncertainty as to “whether our results would apply to patients with mild airflow obstruction or a lower exacerbation risk.”

The study was supported by a grant from the Department of Defense. The authors reported numerous potential conflicts of interest, including receiving grants, personal fees and research funds from various pharmaceutical companies and government entities.
 

SOURCE: Dransfield MT et al. CHEST 2019. 2019 Oct 20. doi: 10.1056/NEJMoa1908142.

A new study has found that beta-blocker treatment did not prevent exacerbations in patients with moderate or severe chronic obstructive pulmonary disease (COPD).

decade3d/Thinkstock

“These results differ from previously reported findings from observational studies suggesting that beta-blockers reduce the risks of exacerbation and death from any cause in patients with COPD,” wrote Mark T. Dransfield, MD, of the University of Alabama at Birmingham and coauthors. Their findings were presented at the annual meeting of the American College of Chest Physicians and also were published simultaneously in the New England Journal of Medicine.

To determine the value of beta-blockers as a potential treatment for COPD, the researchers launched a prospective randomized trial called BLOCK COPD, consisting of 532 patients with moderate or severe COPD. They were assigned to two groups: those receiving extended-release metoprolol (n = 268) and those receiving placebo (n = 264). The mean age of all patients was 65 years.

The groups saw no significant difference in median time until the first exacerbation, which was 202 days (95% confidence interval, 162-282) in the metoprolol group and 222 days (95% CI, 189-295) in the placebo group (hazard ratio, 1.05; 95% CI, 0.84-1.32; P = .66). Metoprolol was associated with a higher risk of severe or very severe exacerbations leading to hospitalization (HR, 1.91; 95% CI, 1.29-2.83). During treatment, there were 11 deaths in the metoprolol group and 5 deaths in the placebo group.

Though there was no evidence of increases in patient-reported adverse events related to metoprolol, more discontinuations did occur in the metoprolol group compared with placebo (11.2% vs. 6.1%).

The authors acknowledged their study’s limitations, chiefly including the fact that the trial was ended early “on the basis of the conditional power analyses and concern about safety.” In addition, the reduction of heart rate and blood pressure in the metoprolol group made it impossible to fully blind the study. Finally, many patients in the trial had already suffered the effects of moderate to severe COPD, including previous hospitalization and the need for supplemental oxygen, leading to uncertainty as to “whether our results would apply to patients with mild airflow obstruction or a lower exacerbation risk.”

The study was supported by a grant from the Department of Defense. The authors reported numerous potential conflicts of interest, including receiving grants, personal fees and research funds from various pharmaceutical companies and government entities.
 

SOURCE: Dransfield MT et al. CHEST 2019. 2019 Oct 20. doi: 10.1056/NEJMoa1908142.

A new study has found that beta-blocker treatment did not prevent exacerbations in patients with moderate or severe chronic obstructive pulmonary disease (COPD).

decade3d/Thinkstock

“These results differ from previously reported findings from observational studies suggesting that beta-blockers reduce the risks of exacerbation and death from any cause in patients with COPD,” wrote Mark T. Dransfield, MD, of the University of Alabama at Birmingham and coauthors. Their findings were presented at the annual meeting of the American College of Chest Physicians and also were published simultaneously in the New England Journal of Medicine.

To determine the value of beta-blockers as a potential treatment for COPD, the researchers launched a prospective randomized trial called BLOCK COPD, consisting of 532 patients with moderate or severe COPD. They were assigned to two groups: those receiving extended-release metoprolol (n = 268) and those receiving placebo (n = 264). The mean age of all patients was 65 years.

The groups saw no significant difference in median time until the first exacerbation, which was 202 days (95% confidence interval, 162-282) in the metoprolol group and 222 days (95% CI, 189-295) in the placebo group (hazard ratio, 1.05; 95% CI, 0.84-1.32; P = .66). Metoprolol was associated with a higher risk of severe or very severe exacerbations leading to hospitalization (HR, 1.91; 95% CI, 1.29-2.83). During treatment, there were 11 deaths in the metoprolol group and 5 deaths in the placebo group.

Though there was no evidence of increases in patient-reported adverse events related to metoprolol, more discontinuations did occur in the metoprolol group compared with placebo (11.2% vs. 6.1%).

The authors acknowledged their study’s limitations, chiefly including the fact that the trial was ended early “on the basis of the conditional power analyses and concern about safety.” In addition, the reduction of heart rate and blood pressure in the metoprolol group made it impossible to fully blind the study. Finally, many patients in the trial had already suffered the effects of moderate to severe COPD, including previous hospitalization and the need for supplemental oxygen, leading to uncertainty as to “whether our results would apply to patients with mild airflow obstruction or a lower exacerbation risk.”

The study was supported by a grant from the Department of Defense. The authors reported numerous potential conflicts of interest, including receiving grants, personal fees and research funds from various pharmaceutical companies and government entities.
 

SOURCE: Dransfield MT et al. CHEST 2019. 2019 Oct 20. doi: 10.1056/NEJMoa1908142.

Influenza vaccination modestly reduces the risk of hospitalizations associated with laboratory-confirmed influenza in people with chronic obstructive pulmonary disease (COPD), according to data published in the Journal of Infectious Diseases.

Cynthia Goldsmith/CDC photo #10073

“To the best of our knowledge, this is the first large, real-world population study to examine vaccine effectiveness in people with COPD using the test-negative design and influenza-specific study outcomes,” wrote Andrea S. Gershon, MD, of Sunnybrook Health Sciences Center in Toronto and colleagues. “These findings emphasize the need for more effective influenza vaccines for older COPD patients and other preventive strategies.”
 

A test-negative study design

Data suggest that 70% of COPD exacerbations are caused by infection, and influenza often is identified as the cause. Although all major COPD practice guidelines recommend seasonal influenza vaccination, the evidence indicating that vaccination reduces hospitalizations and death is limited. The inherent or corticosteroid-induced decrease in immune response to vaccination and respiratory infection among patients with COPD may reduce the effectiveness of influenza vaccination, wrote Dr. Gershon and colleagues.

The investigators used a test-negative design to evaluate how effectively influenza vaccination prevents laboratory-confirmed influenza–associated hospitalizations in community-dwelling older patients with COPD. They chose this design because it attenuates biases resulting from misclassification of infection and from differences in health care–seeking behavior between vaccinated and unvaccinated patients.

Dr. Gershon and colleagues examined health care administrative data and respiratory specimens collected from patients who had been tested for influenza during the 2010-2011 to 2015-2016 influenza seasons. Eligible patients were aged 66 years or older, had physician-diagnosed COPD, and had been tested for influenza within 3 days before and during an acute care hospitalization. The researchers determined influenza vaccination status using physician and pharmacist billing claims. They obtained demographic information through linkage with the provincial health insurance database. Multivariable logistic regression allowed Dr. Gershon and colleagues to estimate the adjusted odds ratio of influenza vaccination in people with laboratory-confirmed influenza, compared with those without.
 

Effectiveness did not vary by demographic factors

The investigators included 21,748 patients in their analysis. Of this population, 3,636 (16.7%) patients tested positive for influenza. Vaccinated patients were less likely than unvaccinated patients to test positive for influenza (15.3% vs. 18.6%). Vaccinated patients also were more likely to be older; live in an urban area; live in a higher income neighborhood; have had more outpatient visits with a physician in the previous year; have received a prescription for a COPD medication in the previous 6 months; have diabetes, asthma, or immunocompromising conditions; have a longer duration of COPD; and have had an outpatient COPD exacerbation in the previous year.

The overall unadjusted estimate of vaccine effectiveness against laboratory-confirmed influenza–associated hospitalizations was 21%. Multivariable adjustment yielded an effectiveness of 22%. When Dr. Gershon and colleagues corrected for misclassification of vaccination status among people with COPD, the effectiveness was estimated to be 43%. Vaccine effectiveness did not vary significantly according to influenza season, nor did it vary significantly by patient-specific factors such as age, sex, influenza subtype, codiagnosis of asthma, duration of COPD, previous outpatient COPD exacerbations, previous COPD hospitalization, previous receipt of inhaled corticosteroids, and previous pneumonia.

One limitation of the study was the possibility that COPD was misclassified because not all participants underwent pulmonary function testing. In addition, the estimates of vaccine effectiveness in the present study are specific to the outcome of influenza hospitalization and may not be generalizable to vaccine effectiveness estimates of outpatient outcomes, said the investigators. Finally, Dr. Gershon and colleagues could not identify the type of vaccine received.

“Given that a large pragmatic randomized controlled trial evaluating influenza vaccination would be unethical, this is likely the most robust estimate of vaccine effectiveness for hospitalizations in the COPD population to guide influenza vaccine recommendations for patients with COPD,” wrote Dr. Gershon and colleagues.

An Ontario Ministry of Health and Long-Term Care Health Systems Research Fund Capacity Grant and a Canadian Institutes of Health Research operating grant funded this research. One investigator received grants from the Canadian Institutes of Health Research during the study, and others received grants from pharmaceutical companies that were unrelated to this study.

[email protected]

SOURCE: Gershon AS et al. J Infect Dis. 2019 Sep 24. doi: 10.1093/infdis/jiz419.

Influenza vaccination modestly reduces the risk of hospitalizations associated with laboratory-confirmed influenza in people with chronic obstructive pulmonary disease (COPD), according to data published in the Journal of Infectious Diseases.

Cynthia Goldsmith/CDC photo #10073

“To the best of our knowledge, this is the first large, real-world population study to examine vaccine effectiveness in people with COPD using the test-negative design and influenza-specific study outcomes,” wrote Andrea S. Gershon, MD, of Sunnybrook Health Sciences Center in Toronto and colleagues. “These findings emphasize the need for more effective influenza vaccines for older COPD patients and other preventive strategies.”
 

A test-negative study design

Data suggest that 70% of COPD exacerbations are caused by infection, and influenza often is identified as the cause. Although all major COPD practice guidelines recommend seasonal influenza vaccination, the evidence indicating that vaccination reduces hospitalizations and death is limited. The inherent or corticosteroid-induced decrease in immune response to vaccination and respiratory infection among patients with COPD may reduce the effectiveness of influenza vaccination, wrote Dr. Gershon and colleagues.

The investigators used a test-negative design to evaluate how effectively influenza vaccination prevents laboratory-confirmed influenza–associated hospitalizations in community-dwelling older patients with COPD. They chose this design because it attenuates biases resulting from misclassification of infection and from differences in health care–seeking behavior between vaccinated and unvaccinated patients.

Dr. Gershon and colleagues examined health care administrative data and respiratory specimens collected from patients who had been tested for influenza during the 2010-2011 to 2015-2016 influenza seasons. Eligible patients were aged 66 years or older, had physician-diagnosed COPD, and had been tested for influenza within 3 days before and during an acute care hospitalization. The researchers determined influenza vaccination status using physician and pharmacist billing claims. They obtained demographic information through linkage with the provincial health insurance database. Multivariable logistic regression allowed Dr. Gershon and colleagues to estimate the adjusted odds ratio of influenza vaccination in people with laboratory-confirmed influenza, compared with those without.
 

Effectiveness did not vary by demographic factors

The investigators included 21,748 patients in their analysis. Of this population, 3,636 (16.7%) patients tested positive for influenza. Vaccinated patients were less likely than unvaccinated patients to test positive for influenza (15.3% vs. 18.6%). Vaccinated patients also were more likely to be older; live in an urban area; live in a higher income neighborhood; have had more outpatient visits with a physician in the previous year; have received a prescription for a COPD medication in the previous 6 months; have diabetes, asthma, or immunocompromising conditions; have a longer duration of COPD; and have had an outpatient COPD exacerbation in the previous year.

The overall unadjusted estimate of vaccine effectiveness against laboratory-confirmed influenza–associated hospitalizations was 21%. Multivariable adjustment yielded an effectiveness of 22%. When Dr. Gershon and colleagues corrected for misclassification of vaccination status among people with COPD, the effectiveness was estimated to be 43%. Vaccine effectiveness did not vary significantly according to influenza season, nor did it vary significantly by patient-specific factors such as age, sex, influenza subtype, codiagnosis of asthma, duration of COPD, previous outpatient COPD exacerbations, previous COPD hospitalization, previous receipt of inhaled corticosteroids, and previous pneumonia.

One limitation of the study was the possibility that COPD was misclassified because not all participants underwent pulmonary function testing. In addition, the estimates of vaccine effectiveness in the present study are specific to the outcome of influenza hospitalization and may not be generalizable to vaccine effectiveness estimates of outpatient outcomes, said the investigators. Finally, Dr. Gershon and colleagues could not identify the type of vaccine received.

“Given that a large pragmatic randomized controlled trial evaluating influenza vaccination would be unethical, this is likely the most robust estimate of vaccine effectiveness for hospitalizations in the COPD population to guide influenza vaccine recommendations for patients with COPD,” wrote Dr. Gershon and colleagues.

An Ontario Ministry of Health and Long-Term Care Health Systems Research Fund Capacity Grant and a Canadian Institutes of Health Research operating grant funded this research. One investigator received grants from the Canadian Institutes of Health Research during the study, and others received grants from pharmaceutical companies that were unrelated to this study.

[email protected]

SOURCE: Gershon AS et al. J Infect Dis. 2019 Sep 24. doi: 10.1093/infdis/jiz419.

Influenza vaccination modestly reduces the risk of hospitalizations associated with laboratory-confirmed influenza in people with chronic obstructive pulmonary disease (COPD), according to data published in the Journal of Infectious Diseases.

Cynthia Goldsmith/CDC photo #10073

“To the best of our knowledge, this is the first large, real-world population study to examine vaccine effectiveness in people with COPD using the test-negative design and influenza-specific study outcomes,” wrote Andrea S. Gershon, MD, of Sunnybrook Health Sciences Center in Toronto and colleagues. “These findings emphasize the need for more effective influenza vaccines for older COPD patients and other preventive strategies.”
 

A test-negative study design

Data suggest that 70% of COPD exacerbations are caused by infection, and influenza often is identified as the cause. Although all major COPD practice guidelines recommend seasonal influenza vaccination, the evidence indicating that vaccination reduces hospitalizations and death is limited. The inherent or corticosteroid-induced decrease in immune response to vaccination and respiratory infection among patients with COPD may reduce the effectiveness of influenza vaccination, wrote Dr. Gershon and colleagues.

The investigators used a test-negative design to evaluate how effectively influenza vaccination prevents laboratory-confirmed influenza–associated hospitalizations in community-dwelling older patients with COPD. They chose this design because it attenuates biases resulting from misclassification of infection and from differences in health care–seeking behavior between vaccinated and unvaccinated patients.

Dr. Gershon and colleagues examined health care administrative data and respiratory specimens collected from patients who had been tested for influenza during the 2010-2011 to 2015-2016 influenza seasons. Eligible patients were aged 66 years or older, had physician-diagnosed COPD, and had been tested for influenza within 3 days before and during an acute care hospitalization. The researchers determined influenza vaccination status using physician and pharmacist billing claims. They obtained demographic information through linkage with the provincial health insurance database. Multivariable logistic regression allowed Dr. Gershon and colleagues to estimate the adjusted odds ratio of influenza vaccination in people with laboratory-confirmed influenza, compared with those without.
 

Effectiveness did not vary by demographic factors

The investigators included 21,748 patients in their analysis. Of this population, 3,636 (16.7%) patients tested positive for influenza. Vaccinated patients were less likely than unvaccinated patients to test positive for influenza (15.3% vs. 18.6%). Vaccinated patients also were more likely to be older; live in an urban area; live in a higher income neighborhood; have had more outpatient visits with a physician in the previous year; have received a prescription for a COPD medication in the previous 6 months; have diabetes, asthma, or immunocompromising conditions; have a longer duration of COPD; and have had an outpatient COPD exacerbation in the previous year.

The overall unadjusted estimate of vaccine effectiveness against laboratory-confirmed influenza–associated hospitalizations was 21%. Multivariable adjustment yielded an effectiveness of 22%. When Dr. Gershon and colleagues corrected for misclassification of vaccination status among people with COPD, the effectiveness was estimated to be 43%. Vaccine effectiveness did not vary significantly according to influenza season, nor did it vary significantly by patient-specific factors such as age, sex, influenza subtype, codiagnosis of asthma, duration of COPD, previous outpatient COPD exacerbations, previous COPD hospitalization, previous receipt of inhaled corticosteroids, and previous pneumonia.

One limitation of the study was the possibility that COPD was misclassified because not all participants underwent pulmonary function testing. In addition, the estimates of vaccine effectiveness in the present study are specific to the outcome of influenza hospitalization and may not be generalizable to vaccine effectiveness estimates of outpatient outcomes, said the investigators. Finally, Dr. Gershon and colleagues could not identify the type of vaccine received.

“Given that a large pragmatic randomized controlled trial evaluating influenza vaccination would be unethical, this is likely the most robust estimate of vaccine effectiveness for hospitalizations in the COPD population to guide influenza vaccine recommendations for patients with COPD,” wrote Dr. Gershon and colleagues.

An Ontario Ministry of Health and Long-Term Care Health Systems Research Fund Capacity Grant and a Canadian Institutes of Health Research operating grant funded this research. One investigator received grants from the Canadian Institutes of Health Research during the study, and others received grants from pharmaceutical companies that were unrelated to this study.

[email protected]

SOURCE: Gershon AS et al. J Infect Dis. 2019 Sep 24. doi: 10.1093/infdis/jiz419.

Long-term home noninvasive ventilation (LTH-NIV) has conditional value for patients with chronic hypercapnic chronic obstructive pulmonary disease (COPD), according to a new guideline from a European Respiratory Society task force.

“Our recommendations, based on the best available evidence, can guide the management of chronic hypercapnic respiratory failure in COPD patients aimed at improving patient outcomes,” wrote Begum Ergan, MD, of Dokuz Eylul University, Izmir, Turkey, and coauthors. The guideline was published in the European Respiratory Journal.

To provide insight into the clinical application of LTH-NIV, the European Respiratory Society convened a task force of 20 clinicians, methodologists, and experts. Their four recommendations were developed based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology.

The first recommendation was to use LTH-NIV for patients with chronic stable hypercapnic COPD. Though an analysis of randomized, controlled trials showed little effect on mortality or hospitalizations, pooled analyses showed that NIV may decrease dyspnea scores (standardized mean difference, –0.51; 95% confidence interval, –0.06 to –0.95) and increase health-related quality of life (SMD, 0.49; 95% CI, –0.01 to 0.98).

The second was to use LTH-NIV in patients with COPD following a life-threatening episode of acute hypercapnic respiratory failure requiring acute NIV, if hypercapnia persists. Though it was not associated with a reduction in mortality (risk ratio, 0.92; 95% CI, 0.67-1.25), it was found to potentially reduce exacerbations (SMD, 0.19; 95% CI, –0.40 to 0.01) and hospitalizations (RR, 0.61; 95% CI, 0.30-1.24).

The third was to titrate LTH-NIV to normalize or reduce PaCO₂ levels in patients with COPD. While this recommendation was issued with a very low certainty of evidence, it was driven by the “minimal potential harms of targeted PaCO₂ reduction.”

The fourth was to use fixed pressure support mode as first-choice ventilator mode in patients with COPD using LTH-NIV. The six trials on this subject did not provide insight into long-term outcomes, nor were there significant improvements seen in health-related quality of life, sleep quality, or exercise tolerance. As such, it was also issued with a very low certainty of evidence.

The authors acknowledged all four recommendations as weak and conditional, “due to limitations in the certainty of the available evidence.” As such, they noted that their recommendations “require consideration of individual preferences, resource considerations, technical expertise, and clinical circumstances prior to implementation in clinical practice.”

The authors reported numerous disclosures, including receiving grants and personal fees from various medical supply companies.

SOURCE: Ergan B et al. Eur Respir J. 2019 Aug 29. doi: 10.1183/13993003.01003-2019.

Long-term home noninvasive ventilation (LTH-NIV) has conditional value for patients with chronic hypercapnic chronic obstructive pulmonary disease (COPD), according to a new guideline from a European Respiratory Society task force.

“Our recommendations, based on the best available evidence, can guide the management of chronic hypercapnic respiratory failure in COPD patients aimed at improving patient outcomes,” wrote Begum Ergan, MD, of Dokuz Eylul University, Izmir, Turkey, and coauthors. The guideline was published in the European Respiratory Journal.

To provide insight into the clinical application of LTH-NIV, the European Respiratory Society convened a task force of 20 clinicians, methodologists, and experts. Their four recommendations were developed based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology.

The first recommendation was to use LTH-NIV for patients with chronic stable hypercapnic COPD. Though an analysis of randomized, controlled trials showed little effect on mortality or hospitalizations, pooled analyses showed that NIV may decrease dyspnea scores (standardized mean difference, –0.51; 95% confidence interval, –0.06 to –0.95) and increase health-related quality of life (SMD, 0.49; 95% CI, –0.01 to 0.98).

The second was to use LTH-NIV in patients with COPD following a life-threatening episode of acute hypercapnic respiratory failure requiring acute NIV, if hypercapnia persists. Though it was not associated with a reduction in mortality (risk ratio, 0.92; 95% CI, 0.67-1.25), it was found to potentially reduce exacerbations (SMD, 0.19; 95% CI, –0.40 to 0.01) and hospitalizations (RR, 0.61; 95% CI, 0.30-1.24).

The third was to titrate LTH-NIV to normalize or reduce PaCO₂ levels in patients with COPD. While this recommendation was issued with a very low certainty of evidence, it was driven by the “minimal potential harms of targeted PaCO₂ reduction.”

The fourth was to use fixed pressure support mode as first-choice ventilator mode in patients with COPD using LTH-NIV. The six trials on this subject did not provide insight into long-term outcomes, nor were there significant improvements seen in health-related quality of life, sleep quality, or exercise tolerance. As such, it was also issued with a very low certainty of evidence.

The authors acknowledged all four recommendations as weak and conditional, “due to limitations in the certainty of the available evidence.” As such, they noted that their recommendations “require consideration of individual preferences, resource considerations, technical expertise, and clinical circumstances prior to implementation in clinical practice.”

The authors reported numerous disclosures, including receiving grants and personal fees from various medical supply companies.

SOURCE: Ergan B et al. Eur Respir J. 2019 Aug 29. doi: 10.1183/13993003.01003-2019.

Long-term home noninvasive ventilation (LTH-NIV) has conditional value for patients with chronic hypercapnic chronic obstructive pulmonary disease (COPD), according to a new guideline from a European Respiratory Society task force.

“Our recommendations, based on the best available evidence, can guide the management of chronic hypercapnic respiratory failure in COPD patients aimed at improving patient outcomes,” wrote Begum Ergan, MD, of Dokuz Eylul University, Izmir, Turkey, and coauthors. The guideline was published in the European Respiratory Journal.

To provide insight into the clinical application of LTH-NIV, the European Respiratory Society convened a task force of 20 clinicians, methodologists, and experts. Their four recommendations were developed based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology.

The first recommendation was to use LTH-NIV for patients with chronic stable hypercapnic COPD. Though an analysis of randomized, controlled trials showed little effect on mortality or hospitalizations, pooled analyses showed that NIV may decrease dyspnea scores (standardized mean difference, –0.51; 95% confidence interval, –0.06 to –0.95) and increase health-related quality of life (SMD, 0.49; 95% CI, –0.01 to 0.98).

The second was to use LTH-NIV in patients with COPD following a life-threatening episode of acute hypercapnic respiratory failure requiring acute NIV, if hypercapnia persists. Though it was not associated with a reduction in mortality (risk ratio, 0.92; 95% CI, 0.67-1.25), it was found to potentially reduce exacerbations (SMD, 0.19; 95% CI, –0.40 to 0.01) and hospitalizations (RR, 0.61; 95% CI, 0.30-1.24).

The third was to titrate LTH-NIV to normalize or reduce PaCO₂ levels in patients with COPD. While this recommendation was issued with a very low certainty of evidence, it was driven by the “minimal potential harms of targeted PaCO₂ reduction.”

The fourth was to use fixed pressure support mode as first-choice ventilator mode in patients with COPD using LTH-NIV. The six trials on this subject did not provide insight into long-term outcomes, nor were there significant improvements seen in health-related quality of life, sleep quality, or exercise tolerance. As such, it was also issued with a very low certainty of evidence.

The authors acknowledged all four recommendations as weak and conditional, “due to limitations in the certainty of the available evidence.” As such, they noted that their recommendations “require consideration of individual preferences, resource considerations, technical expertise, and clinical circumstances prior to implementation in clinical practice.”

The authors reported numerous disclosures, including receiving grants and personal fees from various medical supply companies.

SOURCE: Ergan B et al. Eur Respir J. 2019 Aug 29. doi: 10.1183/13993003.01003-2019.

The 2019 wildfire season is underway in many locales across the United States, exposing millions of individuals to smoky conditions that will have health consequences ranging from stinging eyes to scratchy throats to a trip to the ED for asthma or chronic obstructive pulmonary disease (COPD) exacerbation. Questions about long-term health impacts are on the minds of many, including physicians and their patients who live with cardiorespiratory conditions.

US Forest Service photo courtesy of Peter Buschmann.

John R. Balmes, MD, a pulmonologist at the University of California, San Francisco, and an expert on the respiratory and cardiovascular effects of air pollutants, suggested that the best available published literature points to “pretty strong evidence for acute effects of wildfire smoke on respiratory health, meaning people with preexisting asthma and COPD are at risk for exacerbations, and probably for respiratory tract infections as well.” He said, “It’s a little less clear, but there’s good biological plausibility for increased risk of respiratory tract infections because when your alveolar macrophages are overloaded with carbon particles that are toxic to those cells, they don’t function as well as a first line of defense against bacterial infection, for example.”

The new normal of wildfires

Warmer, drier summers in recent years in the western United States and many other regions, attributed by climate experts to global climate change, have produced catastrophic wildfires (PNAS;2016 Oct 18;113[42]11770-5; Science 2006 Aug 18;313:940-3). The Camp Fire in Northern California broke out in November 2018, took the lives of at least 85 people, and cost more than $16 billion in damage. Smoke from that blaze reached hazardous levels in San Francisco, Sacramento, Fresno, and many other smaller towns. Other forest fires in that year caused heavy smoke conditions in Portland, Seattle, Vancouver, and Anchorage. Such events are expected to be repeated often in the coming years (Int J Environ Res Public Health. 2019 Jul 6;16[13]).

Courtesy Dr. Wayne Cascio

Wildfire smoke can contain a wide range of substances, chemicals, and gases with known and unknown cardiorespiratory implications. “Smoke is composed primarily of carbon dioxide, water vapor, carbon monoxide, particulate matter, hydrocarbons and other organic chemicals, nitrogen oxides, trace minerals and several thousand other compounds,” according to the U.S. Environmental Protection Agency (Wildfire smoke: A guide for public health officials 2019. Washington, D.C.: EPA, 2019). The EPA report noted, “Particles with diameters less than 10 mcm (particulate matter, or PM₁₀) can be inhaled into the lungs and affect the lungs, heart, and blood vessels. The smallest particles, those less than 2.5 mcm in diameter (PM_2.5), are the greatest risk to public health because they can reach deep into the lungs and may even make it into the bloodstream.”

Research on health impact

In early June of 2008, Wayne Cascio, MD, awoke in his Greenville, N.C., home to the stench of smoke emanating from a large peat fire burning some 65 miles away. By the time he reached the parking lot at East Carolina University in Greenville to begin his workday as chief of cardiology, the haze of smoke had thickened to the point where he could only see a few feet in front of him.

Over the next several weeks, the fire scorched 41,000 acres and produced haze and air pollution that far exceeded National Ambient Air Quality Standards for particulate matter and blanketed rural communities in the state’s eastern region. The price tag for management of the blaze reached $20 million. Because of his interest in the health effects of wildfire smoke and because of his relationship with investigators at the EPA, Dr. Cascio initiated an epidemiology study to investigate the effects of exposure on cardiorespiratory outcomes in the population affected by the fire (Environ Health Perspect. 2011 Oct;119[10]:1415-20).

By combining satellite data with syndromic surveillance drawn from hospital records in 41 counties contained in the North Carolina Disease Event Tracking and Epidemiologic Collection Tool, he and his colleagues found that exposure to the peat wildfire smoke led to increases in the cumulative risk ratio for asthma (relative risk, 1.65), chronic obstructive pulmonary disease (RR, 1.73), and pneumonia and acute bronchitis (RR, 1.59). ED visits related to cardiopulmonary symptoms and heart failure also were significantly increased (RR, 1.23 and 1.37, respectively). “That was really the first study to strongly identify a cardiac endpoint related to wildfire smoke exposure,” said Dr. Cascio, who now directs the EPA’s National Health and Environmental Effects Research Laboratory. “It really pointed out how little we knew about the health effects of wildfire up until that time.”

Those early findings have been replicated in subsequent research about the acute health effects of exposure to wildfire smoke, which contains PM_2.5 and other toxic substances from structures, electronic devices, and automobiles destroyed in the path of flames, including heavy metals and asbestos. Most of the work has focused on smoke-related cardiovascular and respiratory ED visits and hospitalizations.

A study of the 2008 California wildfire impact on ED visits accounted for ozone levels in addition to PM_2.5 in the smoke. During the active fire periods, PM_2.5 was significantly associated with exacerbations of asthma and COPD and these effects remained after controlling for ozone levels. PM_2.5 inhalation during the wildfires was associated with increased risk of an ED visit for asthma (RR, 1.112; 95% confidence interval, 1.087-1.138) for a 10 mcg/m³ increase in PM_2.5 and COPD (RR, 1.05; 95% CI, 1.019-1.0825), as well as for combined respiratory visits (RR, 1.035; 95% CI, 1.023-1.046) (Environ Int. 2109 Aug;129:291-8).

Researchers who evaluated the health impacts of wildfires in California during the 2015 fire season found an increase in all-cause cardiovascular and respiratory ED visits, especially among those aged 65 years and older during smoke days. The population-based study included 1,196,233 ED visits during May 1–Sept. 30 that year. PM_2.5 concentrations were categorized as light, medium, or dense. Relative risk rose with the amount of smoke in the air. Rates of all-cause cardiovascular ED visits were elevated across levels of smoke density, with the greatest increase on dense smoke days and among those aged 65 years or older (RR,1.15; 95% CI, 1.09-1.22). All-cause cerebrovascular visits were associated with dense smoke days, especially among those aged 65 years and older (RR, 1.22; 95% CI, 1.00-1.49). Respiratory conditions also were increased on dense smoke days (RR, 1.18; 95% CI, 1.08-1.28) (J Am Heart Assoc. 2018 Apr 11;7:e007492. doi: 10.1161/JAHA.117.007492).

Long-term effects unknown

When it comes to the long-term effects of wildfire smoke on human health outcomes, much less is known. In a recent literature review, Colleen E. Reid, PhD, and Melissa May Maestas, PhD, found only one study that investigated long-term respiratory health impacts of wildfire smoke, and only a few studies that have estimated future health impacts of wildfires under likely climate change scenarios (Curr Opin Pulm Med. 2019 Mar;25:179-87).

“We know that there are immediate respiratory health effects from wildfire smoke,” said Dr. Reid of the department of geography at the University of Colorado Boulder. “What’s less known is everything else. That’s challenging, because people want to know about the long-term health effects.”

Evidence from the scientific literature suggests that exposure to air pollution adversely affects cardiovascular health, but whether exposure to wildfire smoke confers a similar risk is less clear. “Until just a few years ago we haven’t been able to study wildfire exposure measures on a large scale,” said EPA scientist Ana G. Rappold, PhD, a statistician there in the environmental public health division of the National Health and Environmental Effects Research Laboratory. “It’s also hard to predict wildfires, so it’s hard to plan for an epidemiologic study if you don’t know where they’re going to occur.”

Dr. Rappold and colleagues examined cardiopulmonary hospitalizations among adults aged 65 years and older in 692 U.S. counties within 200 km of 123 large wildfires during 2008-2010 (Environ Health Perspect. 2019;127[3]:37006. doi: 10.1289/EHP3860). They observed that an increased risk of PM_2.5-related cardiopulmonary hospitalizations was similar on smoke and nonsmoke days across multiple lags and exposure metrics, while risk for asthma-related hospitalizations was higher during smoke days. “One hypothesis is that this was an older study population, so naturally if you’re inhaling smoke, the first organ that’s impacted in an older population is the lungs,” Dr. Rappold said. “If you go to the hospital for asthma, wheezing, or bronchitis, you are taken out of the risk pool for cardiovascular and other diseases. That could explain why in other studies we don’t see a clear cardiovascular signal as we have for air pollution studies in general. Another aspect to this study is, the exposure metric was PM_2.5, but smoke contains many other components, particularly gases, which are respiratory irritants. It could be that this triggers a higher risk for respiratory [effects] than regular episodes of high PM_2.5 exposure, just because of the additional gases that people are exposed to.”

Another complicating factor is the paucity of data about solutions to long-term exposure to wildfire smoke. “If you’re impacted by high-exposure levels for 60 days, that is not something we have experienced before,” Dr. Rappold noted. “What are the solutions for that community? What works? Can we show that by implementing community-level resilience plans with HEPA [high-efficiency particulate air] filters or other interventions, do the overall outcomes improve? Doctors are the first ones to talk with their patients about their symptoms and about how to take care of their conditions. They can clearly make a difference in emphasizing reducing exposures in a way that fits their patients individually, either reducing the amount of time spent outside, the duration of exposure, and the level of exposure. Maybe change activities based on the intensity of exposure. Don’t go for a run outside when it’s smoky, because your ventilation rate is higher and you will breathe in more smoke. Become aware of those things.”

Advising vulnerable patients

While research in this field advances, the unforgiving wildfire season looms, assuring more destruction of property and threats to cardiorespiratory health. “There are a lot of questions that research will have an opportunity to address as we go forward, including the utility and the benefit of N95 masks, the utility of HEPA filters used in the house, and even with HVAC [heating, ventilation, and air conditioning] systems,” Dr. Cascio said. “Can we really clean up the indoor air well enough to protect us from wildfire smoke?”

The way he sees it, the time is ripe for clinicians and officials in public and private practice settings to refine how they distribute information to people living in areas affected by wildfire smoke. “We can’t force people do anything, but at least if they’re informed, then they understand they can make an informed decision about how they might want to affect what they do that would limit their exposure,” he said. “As a patient, my health care system sends text and email messages to me. So, why couldn’t the hospital send out a text message or an email to all of the patients with COPD, coronary disease, and heart failure when an area is impacted by smoke, saying, ‘Check your air quality and take action if air quality is poor?’ Physicians don’t have time to do this kind of education in the office for all of their patients. I know that from experience. But if one were to only focus on those at highest risk, and encourage them to follow our guidelines, which might include doing HEPA filter treatment in the home, we probably would reduce the number of clinical events in a cost-effective way.”

[email protected]

The 2019 wildfire season is underway in many locales across the United States, exposing millions of individuals to smoky conditions that will have health consequences ranging from stinging eyes to scratchy throats to a trip to the ED for asthma or chronic obstructive pulmonary disease (COPD) exacerbation. Questions about long-term health impacts are on the minds of many, including physicians and their patients who live with cardiorespiratory conditions.

US Forest Service photo courtesy of Peter Buschmann.

John R. Balmes, MD, a pulmonologist at the University of California, San Francisco, and an expert on the respiratory and cardiovascular effects of air pollutants, suggested that the best available published literature points to “pretty strong evidence for acute effects of wildfire smoke on respiratory health, meaning people with preexisting asthma and COPD are at risk for exacerbations, and probably for respiratory tract infections as well.” He said, “It’s a little less clear, but there’s good biological plausibility for increased risk of respiratory tract infections because when your alveolar macrophages are overloaded with carbon particles that are toxic to those cells, they don’t function as well as a first line of defense against bacterial infection, for example.”

The new normal of wildfires

Warmer, drier summers in recent years in the western United States and many other regions, attributed by climate experts to global climate change, have produced catastrophic wildfires (PNAS;2016 Oct 18;113[42]11770-5; Science 2006 Aug 18;313:940-3). The Camp Fire in Northern California broke out in November 2018, took the lives of at least 85 people, and cost more than $16 billion in damage. Smoke from that blaze reached hazardous levels in San Francisco, Sacramento, Fresno, and many other smaller towns. Other forest fires in that year caused heavy smoke conditions in Portland, Seattle, Vancouver, and Anchorage. Such events are expected to be repeated often in the coming years (Int J Environ Res Public Health. 2019 Jul 6;16[13]).

Courtesy Dr. Wayne Cascio

Wildfire smoke can contain a wide range of substances, chemicals, and gases with known and unknown cardiorespiratory implications. “Smoke is composed primarily of carbon dioxide, water vapor, carbon monoxide, particulate matter, hydrocarbons and other organic chemicals, nitrogen oxides, trace minerals and several thousand other compounds,” according to the U.S. Environmental Protection Agency (Wildfire smoke: A guide for public health officials 2019. Washington, D.C.: EPA, 2019). The EPA report noted, “Particles with diameters less than 10 mcm (particulate matter, or PM₁₀) can be inhaled into the lungs and affect the lungs, heart, and blood vessels. The smallest particles, those less than 2.5 mcm in diameter (PM_2.5), are the greatest risk to public health because they can reach deep into the lungs and may even make it into the bloodstream.”

Research on health impact

In early June of 2008, Wayne Cascio, MD, awoke in his Greenville, N.C., home to the stench of smoke emanating from a large peat fire burning some 65 miles away. By the time he reached the parking lot at East Carolina University in Greenville to begin his workday as chief of cardiology, the haze of smoke had thickened to the point where he could only see a few feet in front of him.

Over the next several weeks, the fire scorched 41,000 acres and produced haze and air pollution that far exceeded National Ambient Air Quality Standards for particulate matter and blanketed rural communities in the state’s eastern region. The price tag for management of the blaze reached $20 million. Because of his interest in the health effects of wildfire smoke and because of his relationship with investigators at the EPA, Dr. Cascio initiated an epidemiology study to investigate the effects of exposure on cardiorespiratory outcomes in the population affected by the fire (Environ Health Perspect. 2011 Oct;119[10]:1415-20).

By combining satellite data with syndromic surveillance drawn from hospital records in 41 counties contained in the North Carolina Disease Event Tracking and Epidemiologic Collection Tool, he and his colleagues found that exposure to the peat wildfire smoke led to increases in the cumulative risk ratio for asthma (relative risk, 1.65), chronic obstructive pulmonary disease (RR, 1.73), and pneumonia and acute bronchitis (RR, 1.59). ED visits related to cardiopulmonary symptoms and heart failure also were significantly increased (RR, 1.23 and 1.37, respectively). “That was really the first study to strongly identify a cardiac endpoint related to wildfire smoke exposure,” said Dr. Cascio, who now directs the EPA’s National Health and Environmental Effects Research Laboratory. “It really pointed out how little we knew about the health effects of wildfire up until that time.”

Those early findings have been replicated in subsequent research about the acute health effects of exposure to wildfire smoke, which contains PM_2.5 and other toxic substances from structures, electronic devices, and automobiles destroyed in the path of flames, including heavy metals and asbestos. Most of the work has focused on smoke-related cardiovascular and respiratory ED visits and hospitalizations.

A study of the 2008 California wildfire impact on ED visits accounted for ozone levels in addition to PM_2.5 in the smoke. During the active fire periods, PM_2.5 was significantly associated with exacerbations of asthma and COPD and these effects remained after controlling for ozone levels. PM_2.5 inhalation during the wildfires was associated with increased risk of an ED visit for asthma (RR, 1.112; 95% confidence interval, 1.087-1.138) for a 10 mcg/m³ increase in PM_2.5 and COPD (RR, 1.05; 95% CI, 1.019-1.0825), as well as for combined respiratory visits (RR, 1.035; 95% CI, 1.023-1.046) (Environ Int. 2109 Aug;129:291-8).

Researchers who evaluated the health impacts of wildfires in California during the 2015 fire season found an increase in all-cause cardiovascular and respiratory ED visits, especially among those aged 65 years and older during smoke days. The population-based study included 1,196,233 ED visits during May 1–Sept. 30 that year. PM_2.5 concentrations were categorized as light, medium, or dense. Relative risk rose with the amount of smoke in the air. Rates of all-cause cardiovascular ED visits were elevated across levels of smoke density, with the greatest increase on dense smoke days and among those aged 65 years or older (RR,1.15; 95% CI, 1.09-1.22). All-cause cerebrovascular visits were associated with dense smoke days, especially among those aged 65 years and older (RR, 1.22; 95% CI, 1.00-1.49). Respiratory conditions also were increased on dense smoke days (RR, 1.18; 95% CI, 1.08-1.28) (J Am Heart Assoc. 2018 Apr 11;7:e007492. doi: 10.1161/JAHA.117.007492).

Long-term effects unknown

When it comes to the long-term effects of wildfire smoke on human health outcomes, much less is known. In a recent literature review, Colleen E. Reid, PhD, and Melissa May Maestas, PhD, found only one study that investigated long-term respiratory health impacts of wildfire smoke, and only a few studies that have estimated future health impacts of wildfires under likely climate change scenarios (Curr Opin Pulm Med. 2019 Mar;25:179-87).

“We know that there are immediate respiratory health effects from wildfire smoke,” said Dr. Reid of the department of geography at the University of Colorado Boulder. “What’s less known is everything else. That’s challenging, because people want to know about the long-term health effects.”

Evidence from the scientific literature suggests that exposure to air pollution adversely affects cardiovascular health, but whether exposure to wildfire smoke confers a similar risk is less clear. “Until just a few years ago we haven’t been able to study wildfire exposure measures on a large scale,” said EPA scientist Ana G. Rappold, PhD, a statistician there in the environmental public health division of the National Health and Environmental Effects Research Laboratory. “It’s also hard to predict wildfires, so it’s hard to plan for an epidemiologic study if you don’t know where they’re going to occur.”

Dr. Rappold and colleagues examined cardiopulmonary hospitalizations among adults aged 65 years and older in 692 U.S. counties within 200 km of 123 large wildfires during 2008-2010 (Environ Health Perspect. 2019;127[3]:37006. doi: 10.1289/EHP3860). They observed that an increased risk of PM_2.5-related cardiopulmonary hospitalizations was similar on smoke and nonsmoke days across multiple lags and exposure metrics, while risk for asthma-related hospitalizations was higher during smoke days. “One hypothesis is that this was an older study population, so naturally if you’re inhaling smoke, the first organ that’s impacted in an older population is the lungs,” Dr. Rappold said. “If you go to the hospital for asthma, wheezing, or bronchitis, you are taken out of the risk pool for cardiovascular and other diseases. That could explain why in other studies we don’t see a clear cardiovascular signal as we have for air pollution studies in general. Another aspect to this study is, the exposure metric was PM_2.5, but smoke contains many other components, particularly gases, which are respiratory irritants. It could be that this triggers a higher risk for respiratory [effects] than regular episodes of high PM_2.5 exposure, just because of the additional gases that people are exposed to.”

Another complicating factor is the paucity of data about solutions to long-term exposure to wildfire smoke. “If you’re impacted by high-exposure levels for 60 days, that is not something we have experienced before,” Dr. Rappold noted. “What are the solutions for that community? What works? Can we show that by implementing community-level resilience plans with HEPA [high-efficiency particulate air] filters or other interventions, do the overall outcomes improve? Doctors are the first ones to talk with their patients about their symptoms and about how to take care of their conditions. They can clearly make a difference in emphasizing reducing exposures in a way that fits their patients individually, either reducing the amount of time spent outside, the duration of exposure, and the level of exposure. Maybe change activities based on the intensity of exposure. Don’t go for a run outside when it’s smoky, because your ventilation rate is higher and you will breathe in more smoke. Become aware of those things.”

Advising vulnerable patients

While research in this field advances, the unforgiving wildfire season looms, assuring more destruction of property and threats to cardiorespiratory health. “There are a lot of questions that research will have an opportunity to address as we go forward, including the utility and the benefit of N95 masks, the utility of HEPA filters used in the house, and even with HVAC [heating, ventilation, and air conditioning] systems,” Dr. Cascio said. “Can we really clean up the indoor air well enough to protect us from wildfire smoke?”

The way he sees it, the time is ripe for clinicians and officials in public and private practice settings to refine how they distribute information to people living in areas affected by wildfire smoke. “We can’t force people do anything, but at least if they’re informed, then they understand they can make an informed decision about how they might want to affect what they do that would limit their exposure,” he said. “As a patient, my health care system sends text and email messages to me. So, why couldn’t the hospital send out a text message or an email to all of the patients with COPD, coronary disease, and heart failure when an area is impacted by smoke, saying, ‘Check your air quality and take action if air quality is poor?’ Physicians don’t have time to do this kind of education in the office for all of their patients. I know that from experience. But if one were to only focus on those at highest risk, and encourage them to follow our guidelines, which might include doing HEPA filter treatment in the home, we probably would reduce the number of clinical events in a cost-effective way.”

[email protected]

The 2019 wildfire season is underway in many locales across the United States, exposing millions of individuals to smoky conditions that will have health consequences ranging from stinging eyes to scratchy throats to a trip to the ED for asthma or chronic obstructive pulmonary disease (COPD) exacerbation. Questions about long-term health impacts are on the minds of many, including physicians and their patients who live with cardiorespiratory conditions.

US Forest Service photo courtesy of Peter Buschmann.

John R. Balmes, MD, a pulmonologist at the University of California, San Francisco, and an expert on the respiratory and cardiovascular effects of air pollutants, suggested that the best available published literature points to “pretty strong evidence for acute effects of wildfire smoke on respiratory health, meaning people with preexisting asthma and COPD are at risk for exacerbations, and probably for respiratory tract infections as well.” He said, “It’s a little less clear, but there’s good biological plausibility for increased risk of respiratory tract infections because when your alveolar macrophages are overloaded with carbon particles that are toxic to those cells, they don’t function as well as a first line of defense against bacterial infection, for example.”

The new normal of wildfires

Warmer, drier summers in recent years in the western United States and many other regions, attributed by climate experts to global climate change, have produced catastrophic wildfires (PNAS;2016 Oct 18;113[42]11770-5; Science 2006 Aug 18;313:940-3). The Camp Fire in Northern California broke out in November 2018, took the lives of at least 85 people, and cost more than $16 billion in damage. Smoke from that blaze reached hazardous levels in San Francisco, Sacramento, Fresno, and many other smaller towns. Other forest fires in that year caused heavy smoke conditions in Portland, Seattle, Vancouver, and Anchorage. Such events are expected to be repeated often in the coming years (Int J Environ Res Public Health. 2019 Jul 6;16[13]).

Courtesy Dr. Wayne Cascio

Wildfire smoke can contain a wide range of substances, chemicals, and gases with known and unknown cardiorespiratory implications. “Smoke is composed primarily of carbon dioxide, water vapor, carbon monoxide, particulate matter, hydrocarbons and other organic chemicals, nitrogen oxides, trace minerals and several thousand other compounds,” according to the U.S. Environmental Protection Agency (Wildfire smoke: A guide for public health officials 2019. Washington, D.C.: EPA, 2019). The EPA report noted, “Particles with diameters less than 10 mcm (particulate matter, or PM₁₀) can be inhaled into the lungs and affect the lungs, heart, and blood vessels. The smallest particles, those less than 2.5 mcm in diameter (PM_2.5), are the greatest risk to public health because they can reach deep into the lungs and may even make it into the bloodstream.”

Research on health impact

In early June of 2008, Wayne Cascio, MD, awoke in his Greenville, N.C., home to the stench of smoke emanating from a large peat fire burning some 65 miles away. By the time he reached the parking lot at East Carolina University in Greenville to begin his workday as chief of cardiology, the haze of smoke had thickened to the point where he could only see a few feet in front of him.

Over the next several weeks, the fire scorched 41,000 acres and produced haze and air pollution that far exceeded National Ambient Air Quality Standards for particulate matter and blanketed rural communities in the state’s eastern region. The price tag for management of the blaze reached $20 million. Because of his interest in the health effects of wildfire smoke and because of his relationship with investigators at the EPA, Dr. Cascio initiated an epidemiology study to investigate the effects of exposure on cardiorespiratory outcomes in the population affected by the fire (Environ Health Perspect. 2011 Oct;119[10]:1415-20).

By combining satellite data with syndromic surveillance drawn from hospital records in 41 counties contained in the North Carolina Disease Event Tracking and Epidemiologic Collection Tool, he and his colleagues found that exposure to the peat wildfire smoke led to increases in the cumulative risk ratio for asthma (relative risk, 1.65), chronic obstructive pulmonary disease (RR, 1.73), and pneumonia and acute bronchitis (RR, 1.59). ED visits related to cardiopulmonary symptoms and heart failure also were significantly increased (RR, 1.23 and 1.37, respectively). “That was really the first study to strongly identify a cardiac endpoint related to wildfire smoke exposure,” said Dr. Cascio, who now directs the EPA’s National Health and Environmental Effects Research Laboratory. “It really pointed out how little we knew about the health effects of wildfire up until that time.”

Those early findings have been replicated in subsequent research about the acute health effects of exposure to wildfire smoke, which contains PM_2.5 and other toxic substances from structures, electronic devices, and automobiles destroyed in the path of flames, including heavy metals and asbestos. Most of the work has focused on smoke-related cardiovascular and respiratory ED visits and hospitalizations.

A study of the 2008 California wildfire impact on ED visits accounted for ozone levels in addition to PM_2.5 in the smoke. During the active fire periods, PM_2.5 was significantly associated with exacerbations of asthma and COPD and these effects remained after controlling for ozone levels. PM_2.5 inhalation during the wildfires was associated with increased risk of an ED visit for asthma (RR, 1.112; 95% confidence interval, 1.087-1.138) for a 10 mcg/m³ increase in PM_2.5 and COPD (RR, 1.05; 95% CI, 1.019-1.0825), as well as for combined respiratory visits (RR, 1.035; 95% CI, 1.023-1.046) (Environ Int. 2109 Aug;129:291-8).

Researchers who evaluated the health impacts of wildfires in California during the 2015 fire season found an increase in all-cause cardiovascular and respiratory ED visits, especially among those aged 65 years and older during smoke days. The population-based study included 1,196,233 ED visits during May 1–Sept. 30 that year. PM_2.5 concentrations were categorized as light, medium, or dense. Relative risk rose with the amount of smoke in the air. Rates of all-cause cardiovascular ED visits were elevated across levels of smoke density, with the greatest increase on dense smoke days and among those aged 65 years or older (RR,1.15; 95% CI, 1.09-1.22). All-cause cerebrovascular visits were associated with dense smoke days, especially among those aged 65 years and older (RR, 1.22; 95% CI, 1.00-1.49). Respiratory conditions also were increased on dense smoke days (RR, 1.18; 95% CI, 1.08-1.28) (J Am Heart Assoc. 2018 Apr 11;7:e007492. doi: 10.1161/JAHA.117.007492).

Long-term effects unknown

When it comes to the long-term effects of wildfire smoke on human health outcomes, much less is known. In a recent literature review, Colleen E. Reid, PhD, and Melissa May Maestas, PhD, found only one study that investigated long-term respiratory health impacts of wildfire smoke, and only a few studies that have estimated future health impacts of wildfires under likely climate change scenarios (Curr Opin Pulm Med. 2019 Mar;25:179-87).

“We know that there are immediate respiratory health effects from wildfire smoke,” said Dr. Reid of the department of geography at the University of Colorado Boulder. “What’s less known is everything else. That’s challenging, because people want to know about the long-term health effects.”

Evidence from the scientific literature suggests that exposure to air pollution adversely affects cardiovascular health, but whether exposure to wildfire smoke confers a similar risk is less clear. “Until just a few years ago we haven’t been able to study wildfire exposure measures on a large scale,” said EPA scientist Ana G. Rappold, PhD, a statistician there in the environmental public health division of the National Health and Environmental Effects Research Laboratory. “It’s also hard to predict wildfires, so it’s hard to plan for an epidemiologic study if you don’t know where they’re going to occur.”

Dr. Rappold and colleagues examined cardiopulmonary hospitalizations among adults aged 65 years and older in 692 U.S. counties within 200 km of 123 large wildfires during 2008-2010 (Environ Health Perspect. 2019;127[3]:37006. doi: 10.1289/EHP3860). They observed that an increased risk of PM_2.5-related cardiopulmonary hospitalizations was similar on smoke and nonsmoke days across multiple lags and exposure metrics, while risk for asthma-related hospitalizations was higher during smoke days. “One hypothesis is that this was an older study population, so naturally if you’re inhaling smoke, the first organ that’s impacted in an older population is the lungs,” Dr. Rappold said. “If you go to the hospital for asthma, wheezing, or bronchitis, you are taken out of the risk pool for cardiovascular and other diseases. That could explain why in other studies we don’t see a clear cardiovascular signal as we have for air pollution studies in general. Another aspect to this study is, the exposure metric was PM_2.5, but smoke contains many other components, particularly gases, which are respiratory irritants. It could be that this triggers a higher risk for respiratory [effects] than regular episodes of high PM_2.5 exposure, just because of the additional gases that people are exposed to.”

Another complicating factor is the paucity of data about solutions to long-term exposure to wildfire smoke. “If you’re impacted by high-exposure levels for 60 days, that is not something we have experienced before,” Dr. Rappold noted. “What are the solutions for that community? What works? Can we show that by implementing community-level resilience plans with HEPA [high-efficiency particulate air] filters or other interventions, do the overall outcomes improve? Doctors are the first ones to talk with their patients about their symptoms and about how to take care of their conditions. They can clearly make a difference in emphasizing reducing exposures in a way that fits their patients individually, either reducing the amount of time spent outside, the duration of exposure, and the level of exposure. Maybe change activities based on the intensity of exposure. Don’t go for a run outside when it’s smoky, because your ventilation rate is higher and you will breathe in more smoke. Become aware of those things.”

Advising vulnerable patients

While research in this field advances, the unforgiving wildfire season looms, assuring more destruction of property and threats to cardiorespiratory health. “There are a lot of questions that research will have an opportunity to address as we go forward, including the utility and the benefit of N95 masks, the utility of HEPA filters used in the house, and even with HVAC [heating, ventilation, and air conditioning] systems,” Dr. Cascio said. “Can we really clean up the indoor air well enough to protect us from wildfire smoke?”

The way he sees it, the time is ripe for clinicians and officials in public and private practice settings to refine how they distribute information to people living in areas affected by wildfire smoke. “We can’t force people do anything, but at least if they’re informed, then they understand they can make an informed decision about how they might want to affect what they do that would limit their exposure,” he said. “As a patient, my health care system sends text and email messages to me. So, why couldn’t the hospital send out a text message or an email to all of the patients with COPD, coronary disease, and heart failure when an area is impacted by smoke, saying, ‘Check your air quality and take action if air quality is poor?’ Physicians don’t have time to do this kind of education in the office for all of their patients. I know that from experience. But if one were to only focus on those at highest risk, and encourage them to follow our guidelines, which might include doing HEPA filter treatment in the home, we probably would reduce the number of clinical events in a cost-effective way.”

[email protected]

Add-on benralizumab is not associated with a significantly lower annualized rate of exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and eosinophilic inflammation, according to results from two phase 3 trials. The data were published in the New England Journal of Medicine.

Benralizumab, an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody, is approved for the treatment of patients with severe eosinophilic asthma. To assess whether the treatment may prevent COPD exacerbations, Gerard J. Criner, MD, chair and professor of thoracic medicine and surgery at Temple University in Philadelphia and colleagues conducted two randomized, double-blind, parallel-group studies: GALATHEA and TERRANOVA. Researchers enrolled patients with frequent moderate or severe COPD exacerbations and blood eosinophil counts of at least 220 per mm³.

A 56-week treatment period

“An eosinophil threshold of 220 per mm³ was selected on the basis of the phase 2 trial of benralizumab in patients with COPD, in which modeling of annual exacerbations according to baseline blood eosinophil count indicated that patients with eosinophil counts above a similar threshold were more likely to have a response to benralizumab,” the authors wrote. “The doses selected were 30 mg, the approved dose for asthma treatment; 100 mg, to inform the safety margin; and 10 mg (in TERRANOVA), to evaluate the dose-efficacy relationship.”

Patients received placebo or benralizumab via subcutaneous injection every 4 weeks for the first three doses, then every 8 weeks for the rest of the 56-week treatment period. The primary end point was the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56.

The primary analysis populations included 1,120 patients in GALATHEA and 1,545 patients in TERRANOVA. Most patients were white men, and the average age was 65 years. The percentages of patients with current asthma (5.4% in GALATHEA and 3.3% in TERRANOVA) or past asthma (8.3% in GALATHEA and 6.1% in TERRANOVA) were low.

In GALATHEA, the estimated annualized exacerbation rates were 1.19 per year in the 30-mg benralizumab group, 1.03 per year in the 100-mg benralizumab group, and 1.24 per year in the placebo group. Compared with placebo, the rate ratio was 0.96 for 30 mg of benralizumab and 0.83 for 100 mg of benralizumab.

In TERRANOVA, the estimated annualized exacerbation rates for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year, 1.21 per year, 1.09 per year, and 1.17 per year, respectively. The corresponding rate ratios were 0.85, 1.04, and 0.93. “At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial,” the researchers said. “Types and frequencies of adverse events were similar with benralizumab and placebo.”

Depletion of eosinophils in blood and sputum

By week 4, benralizumab substantially depleted blood eosinophils. In addition, treatment substantially depleted sputum eosinophils by week 24. “However, in contrast to the results in benralizumab-treated patients with severe eosinophilic asthma, this eosinophil depletion did not correspond to a significant difference in the rate of exacerbations. This finding, together with the effect on eosinophils – with minimal effect on the COPD exacerbation rate – that was observed in the mepolizumab trials, suggests that eosinophil depletion is unlikely to ameliorate exacerbation outcomes for the majority of patients with COPD,” Dr. Criner and his coauthors concluded. “Future investigation is required to identify additional clinical factors or biomarkers that may characterize the patients with COPD who are most likely to benefit from anti–interleukin-5 receptor antibody therapy.”

The trials were sponsored by AstraZeneca, which manufactures benralizumab (Fasenra), and by Kyowa Hakko Kirin. One author is supported by the National Institute for Health Research Manchester Biomedical Research Centre. The authors’ disclosures included grants and personal fees from AstraZeneca and other pharmaceutical companies.

[email protected]

SOURCE: Criner GJ et al. N Engl J Med. 2019;382(11):1023-34. doi: 10.1056/NEJMoa1905248.

Add-on benralizumab is not associated with a significantly lower annualized rate of exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and eosinophilic inflammation, according to results from two phase 3 trials. The data were published in the New England Journal of Medicine.

Benralizumab, an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody, is approved for the treatment of patients with severe eosinophilic asthma. To assess whether the treatment may prevent COPD exacerbations, Gerard J. Criner, MD, chair and professor of thoracic medicine and surgery at Temple University in Philadelphia and colleagues conducted two randomized, double-blind, parallel-group studies: GALATHEA and TERRANOVA. Researchers enrolled patients with frequent moderate or severe COPD exacerbations and blood eosinophil counts of at least 220 per mm³.

A 56-week treatment period

“An eosinophil threshold of 220 per mm³ was selected on the basis of the phase 2 trial of benralizumab in patients with COPD, in which modeling of annual exacerbations according to baseline blood eosinophil count indicated that patients with eosinophil counts above a similar threshold were more likely to have a response to benralizumab,” the authors wrote. “The doses selected were 30 mg, the approved dose for asthma treatment; 100 mg, to inform the safety margin; and 10 mg (in TERRANOVA), to evaluate the dose-efficacy relationship.”

Patients received placebo or benralizumab via subcutaneous injection every 4 weeks for the first three doses, then every 8 weeks for the rest of the 56-week treatment period. The primary end point was the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56.

The primary analysis populations included 1,120 patients in GALATHEA and 1,545 patients in TERRANOVA. Most patients were white men, and the average age was 65 years. The percentages of patients with current asthma (5.4% in GALATHEA and 3.3% in TERRANOVA) or past asthma (8.3% in GALATHEA and 6.1% in TERRANOVA) were low.

In GALATHEA, the estimated annualized exacerbation rates were 1.19 per year in the 30-mg benralizumab group, 1.03 per year in the 100-mg benralizumab group, and 1.24 per year in the placebo group. Compared with placebo, the rate ratio was 0.96 for 30 mg of benralizumab and 0.83 for 100 mg of benralizumab.

In TERRANOVA, the estimated annualized exacerbation rates for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year, 1.21 per year, 1.09 per year, and 1.17 per year, respectively. The corresponding rate ratios were 0.85, 1.04, and 0.93. “At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial,” the researchers said. “Types and frequencies of adverse events were similar with benralizumab and placebo.”

Depletion of eosinophils in blood and sputum

By week 4, benralizumab substantially depleted blood eosinophils. In addition, treatment substantially depleted sputum eosinophils by week 24. “However, in contrast to the results in benralizumab-treated patients with severe eosinophilic asthma, this eosinophil depletion did not correspond to a significant difference in the rate of exacerbations. This finding, together with the effect on eosinophils – with minimal effect on the COPD exacerbation rate – that was observed in the mepolizumab trials, suggests that eosinophil depletion is unlikely to ameliorate exacerbation outcomes for the majority of patients with COPD,” Dr. Criner and his coauthors concluded. “Future investigation is required to identify additional clinical factors or biomarkers that may characterize the patients with COPD who are most likely to benefit from anti–interleukin-5 receptor antibody therapy.”

The trials were sponsored by AstraZeneca, which manufactures benralizumab (Fasenra), and by Kyowa Hakko Kirin. One author is supported by the National Institute for Health Research Manchester Biomedical Research Centre. The authors’ disclosures included grants and personal fees from AstraZeneca and other pharmaceutical companies.

[email protected]

SOURCE: Criner GJ et al. N Engl J Med. 2019;382(11):1023-34. doi: 10.1056/NEJMoa1905248.

Add-on benralizumab is not associated with a significantly lower annualized rate of exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and eosinophilic inflammation, according to results from two phase 3 trials. The data were published in the New England Journal of Medicine.

Benralizumab, an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody, is approved for the treatment of patients with severe eosinophilic asthma. To assess whether the treatment may prevent COPD exacerbations, Gerard J. Criner, MD, chair and professor of thoracic medicine and surgery at Temple University in Philadelphia and colleagues conducted two randomized, double-blind, parallel-group studies: GALATHEA and TERRANOVA. Researchers enrolled patients with frequent moderate or severe COPD exacerbations and blood eosinophil counts of at least 220 per mm³.

A 56-week treatment period

“An eosinophil threshold of 220 per mm³ was selected on the basis of the phase 2 trial of benralizumab in patients with COPD, in which modeling of annual exacerbations according to baseline blood eosinophil count indicated that patients with eosinophil counts above a similar threshold were more likely to have a response to benralizumab,” the authors wrote. “The doses selected were 30 mg, the approved dose for asthma treatment; 100 mg, to inform the safety margin; and 10 mg (in TERRANOVA), to evaluate the dose-efficacy relationship.”

Patients received placebo or benralizumab via subcutaneous injection every 4 weeks for the first three doses, then every 8 weeks for the rest of the 56-week treatment period. The primary end point was the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56.

The primary analysis populations included 1,120 patients in GALATHEA and 1,545 patients in TERRANOVA. Most patients were white men, and the average age was 65 years. The percentages of patients with current asthma (5.4% in GALATHEA and 3.3% in TERRANOVA) or past asthma (8.3% in GALATHEA and 6.1% in TERRANOVA) were low.

In GALATHEA, the estimated annualized exacerbation rates were 1.19 per year in the 30-mg benralizumab group, 1.03 per year in the 100-mg benralizumab group, and 1.24 per year in the placebo group. Compared with placebo, the rate ratio was 0.96 for 30 mg of benralizumab and 0.83 for 100 mg of benralizumab.

In TERRANOVA, the estimated annualized exacerbation rates for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year, 1.21 per year, 1.09 per year, and 1.17 per year, respectively. The corresponding rate ratios were 0.85, 1.04, and 0.93. “At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial,” the researchers said. “Types and frequencies of adverse events were similar with benralizumab and placebo.”

Depletion of eosinophils in blood and sputum

By week 4, benralizumab substantially depleted blood eosinophils. In addition, treatment substantially depleted sputum eosinophils by week 24. “However, in contrast to the results in benralizumab-treated patients with severe eosinophilic asthma, this eosinophil depletion did not correspond to a significant difference in the rate of exacerbations. This finding, together with the effect on eosinophils – with minimal effect on the COPD exacerbation rate – that was observed in the mepolizumab trials, suggests that eosinophil depletion is unlikely to ameliorate exacerbation outcomes for the majority of patients with COPD,” Dr. Criner and his coauthors concluded. “Future investigation is required to identify additional clinical factors or biomarkers that may characterize the patients with COPD who are most likely to benefit from anti–interleukin-5 receptor antibody therapy.”

The trials were sponsored by AstraZeneca, which manufactures benralizumab (Fasenra), and by Kyowa Hakko Kirin. One author is supported by the National Institute for Health Research Manchester Biomedical Research Centre. The authors’ disclosures included grants and personal fees from AstraZeneca and other pharmaceutical companies.

[email protected]

SOURCE: Criner GJ et al. N Engl J Med. 2019;382(11):1023-34. doi: 10.1056/NEJMoa1905248.

Among patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), lung function and continuous positive airway pressure (CPAP) use are independent predictors of COPD exacerbations and all‐cause mortality, according to a retrospective cohort study.

“These factors should be taken into account when considering the management and prognosis of these patients,” the researchers said in the Clinical Respiratory Journal.

Prior studies have found that patients with COPD and OSA – that is, with overlap syndrome – “have a substantially greater risk of morbidity and mortality, compared to those with either COPD or OSA alone,” said Philippe E. Jaoude, MD, and Ali A. El Solh, MD, both of the Veterans Affairs Western New York Healthcare System in Buffalo and the University at Buffalo.

To identify factors associated with COPD exacerbation and all‐cause mortality in patients with overlap syndrome, Dr. Jaoude and Dr. El Solh reviewed the electronic health records of patients with simultaneous COPD and OSA. They compared patients with overlap syndrome who had an acute exacerbation of COPD during a 42-month period with a control group of patients with overlap syndrome who did not have exacerbations during that time. Patients with exacerbations and controls were matched 1:1 by age and body mass index.

Eligible patients were aged 42-90 years, had objectively confirmed COPD, and had documented OSA by in-laboratory polysomnography (that is, at least five obstructive apneas and hypopneas per hour). The investigators defined a COPD exacerbation as a sustained worsening of a patient’s respiratory condition that warranted additional treatment.

Of 225 eligible patients, 92 had at least one COPD exacerbation between March 2014 and September 2017. Patients with COPD exacerbation and controls had a mean age of about 68 years. The group of patients with exacerbation had a higher percentage of active smokers (21% vs. 9%) and had poorer lung function (mean forced expiratory volume in 1 second percent predicted: 55.2% vs. 64.5%).

“Although the rate of CPAP adherence between the two groups was not significantly different, the average time of CPAP use was significantly higher in patients with no recorded exacerbation,” the researchers reported – 285.4 min/night versus 238.2 min/night.

In all, 146 patients (79.4%) survived, and 38 patients (20.6%) died during the study period. The crude mortality rate was significantly higher in the group with COPD exacerbations (14% vs. 7%).

“Multivariate logistic regression analysis identified the independent risk factors associated with COPD exacerbations as active smoking, worse airflow limitation, and lower CPAP utilization,” they said. “As for all-cause mortality, a higher burden of comorbidities, worse airflow limitation, and lower time of CPAP use were independently associated with poor outcome.”

The researchers noted that they cannot rule out the possibility that patients who were adherent to CPAP were systematically different from those who were not.

The authors had no conflicts of interest.

[email protected]

SOURCE: Jaoude P et al. Clin Respir J. 2019 Aug 22. doi: 10.1111/crj.13079.

Among patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), lung function and continuous positive airway pressure (CPAP) use are independent predictors of COPD exacerbations and all‐cause mortality, according to a retrospective cohort study.

“These factors should be taken into account when considering the management and prognosis of these patients,” the researchers said in the Clinical Respiratory Journal.

Prior studies have found that patients with COPD and OSA – that is, with overlap syndrome – “have a substantially greater risk of morbidity and mortality, compared to those with either COPD or OSA alone,” said Philippe E. Jaoude, MD, and Ali A. El Solh, MD, both of the Veterans Affairs Western New York Healthcare System in Buffalo and the University at Buffalo.

To identify factors associated with COPD exacerbation and all‐cause mortality in patients with overlap syndrome, Dr. Jaoude and Dr. El Solh reviewed the electronic health records of patients with simultaneous COPD and OSA. They compared patients with overlap syndrome who had an acute exacerbation of COPD during a 42-month period with a control group of patients with overlap syndrome who did not have exacerbations during that time. Patients with exacerbations and controls were matched 1:1 by age and body mass index.

Eligible patients were aged 42-90 years, had objectively confirmed COPD, and had documented OSA by in-laboratory polysomnography (that is, at least five obstructive apneas and hypopneas per hour). The investigators defined a COPD exacerbation as a sustained worsening of a patient’s respiratory condition that warranted additional treatment.

Of 225 eligible patients, 92 had at least one COPD exacerbation between March 2014 and September 2017. Patients with COPD exacerbation and controls had a mean age of about 68 years. The group of patients with exacerbation had a higher percentage of active smokers (21% vs. 9%) and had poorer lung function (mean forced expiratory volume in 1 second percent predicted: 55.2% vs. 64.5%).

“Although the rate of CPAP adherence between the two groups was not significantly different, the average time of CPAP use was significantly higher in patients with no recorded exacerbation,” the researchers reported – 285.4 min/night versus 238.2 min/night.

In all, 146 patients (79.4%) survived, and 38 patients (20.6%) died during the study period. The crude mortality rate was significantly higher in the group with COPD exacerbations (14% vs. 7%).

“Multivariate logistic regression analysis identified the independent risk factors associated with COPD exacerbations as active smoking, worse airflow limitation, and lower CPAP utilization,” they said. “As for all-cause mortality, a higher burden of comorbidities, worse airflow limitation, and lower time of CPAP use were independently associated with poor outcome.”

The researchers noted that they cannot rule out the possibility that patients who were adherent to CPAP were systematically different from those who were not.

The authors had no conflicts of interest.

[email protected]

SOURCE: Jaoude P et al. Clin Respir J. 2019 Aug 22. doi: 10.1111/crj.13079.

Among patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), lung function and continuous positive airway pressure (CPAP) use are independent predictors of COPD exacerbations and all‐cause mortality, according to a retrospective cohort study.

“These factors should be taken into account when considering the management and prognosis of these patients,” the researchers said in the Clinical Respiratory Journal.

Prior studies have found that patients with COPD and OSA – that is, with overlap syndrome – “have a substantially greater risk of morbidity and mortality, compared to those with either COPD or OSA alone,” said Philippe E. Jaoude, MD, and Ali A. El Solh, MD, both of the Veterans Affairs Western New York Healthcare System in Buffalo and the University at Buffalo.

To identify factors associated with COPD exacerbation and all‐cause mortality in patients with overlap syndrome, Dr. Jaoude and Dr. El Solh reviewed the electronic health records of patients with simultaneous COPD and OSA. They compared patients with overlap syndrome who had an acute exacerbation of COPD during a 42-month period with a control group of patients with overlap syndrome who did not have exacerbations during that time. Patients with exacerbations and controls were matched 1:1 by age and body mass index.

Eligible patients were aged 42-90 years, had objectively confirmed COPD, and had documented OSA by in-laboratory polysomnography (that is, at least five obstructive apneas and hypopneas per hour). The investigators defined a COPD exacerbation as a sustained worsening of a patient’s respiratory condition that warranted additional treatment.

Of 225 eligible patients, 92 had at least one COPD exacerbation between March 2014 and September 2017. Patients with COPD exacerbation and controls had a mean age of about 68 years. The group of patients with exacerbation had a higher percentage of active smokers (21% vs. 9%) and had poorer lung function (mean forced expiratory volume in 1 second percent predicted: 55.2% vs. 64.5%).

“Although the rate of CPAP adherence between the two groups was not significantly different, the average time of CPAP use was significantly higher in patients with no recorded exacerbation,” the researchers reported – 285.4 min/night versus 238.2 min/night.

In all, 146 patients (79.4%) survived, and 38 patients (20.6%) died during the study period. The crude mortality rate was significantly higher in the group with COPD exacerbations (14% vs. 7%).

“Multivariate logistic regression analysis identified the independent risk factors associated with COPD exacerbations as active smoking, worse airflow limitation, and lower CPAP utilization,” they said. “As for all-cause mortality, a higher burden of comorbidities, worse airflow limitation, and lower time of CPAP use were independently associated with poor outcome.”

The researchers noted that they cannot rule out the possibility that patients who were adherent to CPAP were systematically different from those who were not.

The authors had no conflicts of interest.

[email protected]

SOURCE: Jaoude P et al. Clin Respir J. 2019 Aug 22. doi: 10.1111/crj.13079.

Short-term opioid use is associated with acute respiratory exacerbation in adults with chronic obstructive pulmonary disease (COPD), according to a study of Medicaid claims data.

The data showed that opioid exposure in the prior 7 days was significantly associated with acute respiratory exacerbation. The odds of exacerbation increased as the morphine-equivalent daily dose increased and as the exposure window decreased.

These results “underline the immediacy of the risk of opioid use,” according to Yiran Rong of the department of pharmacy administration at the University of Mississippi in University and colleagues. Ms. Rong and colleagues reported their findings in the American Journal of Epidemiology.

The researchers analyzed Mississippi Medicaid administrative claims data from 2013-2017, which included 1,354 beneficiaries with 1,972 exacerbation events. The beneficiaries had a mean age of 53.11 years, 69.9% were female, and 59.7% were white. The patients had an average of 1.46 exacerbation events, and 62.27% of these events occurred in patients who had an opioid prescription filled in the previous 7 days.

The researchers compared the frequency and dose of opioid exposure in the 7 days before an exacerbation to the opioid exposure in 10 control periods, each 7 days long.

Opioid exposure in the prior 7 days was associated with an 80.8% increase in the odds of exacerbation. The odds ratio, adjusted for exposure to bronchodilators, corticosteroids, benzodiazepines, and beta-blockers, was 1.81 (95% confidence interval, 1.60-2.05).

Opioid exposure was associated with exacerbation in patients with a single exacerbation event (OR, 1.91; 95% CI, 1.61, 2.27), multiple events (OR, 1.71; 95% CI, 1.45-2.01), events recorded in the emergency department (OR, 2.01; 95% CI, 1.71-2.35), and events recorded in the hospital (OR, 1.47; 95% CI, 1.21-1.79).

The odds of exacerbation increased as the morphine-equivalent daily dose increased. Each 25-mg increase in morphine-equivalent daily dose was associated with an 11.2% increase in the odds of exacerbation (OR, 1.11; 95% CI, 1.04-1.20).

“This dose-response relationship is consistent with previously established evidence … and is indicative of the need for caution in prescribing high doses of opioids to COPD patients,” the researchers wrote.

They also found the odds of exacerbation increased as the exposure window decreased. The OR was 1.74 (95% CI, 1.54-1.97) for opioid exposure in an 8-day window before exacerbation and 2.00 (95% CI, 1.73-2.30) for opioid exposure in a 5-day window before exacerbation.

This suggests that “opioid-induced respiratory depression has a very short-term onset,” according to the researchers.

The team noted that this study has limitations, including its retrospective, observational nature, but the results suggest transient opioid use is associated with acute respiratory exacerbation of COPD.

There was no funding for this study, and none of the researchers declared conflicts of interest.

[email protected]

SOURCE: Rong Y et al. Am J Epidemiol. 2019 Jul 30. doi: 10.1093/aje/kwz169.

Short-term opioid use is associated with acute respiratory exacerbation in adults with chronic obstructive pulmonary disease (COPD), according to a study of Medicaid claims data.

The data showed that opioid exposure in the prior 7 days was significantly associated with acute respiratory exacerbation. The odds of exacerbation increased as the morphine-equivalent daily dose increased and as the exposure window decreased.

These results “underline the immediacy of the risk of opioid use,” according to Yiran Rong of the department of pharmacy administration at the University of Mississippi in University and colleagues. Ms. Rong and colleagues reported their findings in the American Journal of Epidemiology.

The researchers analyzed Mississippi Medicaid administrative claims data from 2013-2017, which included 1,354 beneficiaries with 1,972 exacerbation events. The beneficiaries had a mean age of 53.11 years, 69.9% were female, and 59.7% were white. The patients had an average of 1.46 exacerbation events, and 62.27% of these events occurred in patients who had an opioid prescription filled in the previous 7 days.

The researchers compared the frequency and dose of opioid exposure in the 7 days before an exacerbation to the opioid exposure in 10 control periods, each 7 days long.

Opioid exposure in the prior 7 days was associated with an 80.8% increase in the odds of exacerbation. The odds ratio, adjusted for exposure to bronchodilators, corticosteroids, benzodiazepines, and beta-blockers, was 1.81 (95% confidence interval, 1.60-2.05).

Opioid exposure was associated with exacerbation in patients with a single exacerbation event (OR, 1.91; 95% CI, 1.61, 2.27), multiple events (OR, 1.71; 95% CI, 1.45-2.01), events recorded in the emergency department (OR, 2.01; 95% CI, 1.71-2.35), and events recorded in the hospital (OR, 1.47; 95% CI, 1.21-1.79).

The odds of exacerbation increased as the morphine-equivalent daily dose increased. Each 25-mg increase in morphine-equivalent daily dose was associated with an 11.2% increase in the odds of exacerbation (OR, 1.11; 95% CI, 1.04-1.20).

“This dose-response relationship is consistent with previously established evidence … and is indicative of the need for caution in prescribing high doses of opioids to COPD patients,” the researchers wrote.

They also found the odds of exacerbation increased as the exposure window decreased. The OR was 1.74 (95% CI, 1.54-1.97) for opioid exposure in an 8-day window before exacerbation and 2.00 (95% CI, 1.73-2.30) for opioid exposure in a 5-day window before exacerbation.

This suggests that “opioid-induced respiratory depression has a very short-term onset,” according to the researchers.

The team noted that this study has limitations, including its retrospective, observational nature, but the results suggest transient opioid use is associated with acute respiratory exacerbation of COPD.

There was no funding for this study, and none of the researchers declared conflicts of interest.

[email protected]

SOURCE: Rong Y et al. Am J Epidemiol. 2019 Jul 30. doi: 10.1093/aje/kwz169.

Short-term opioid use is associated with acute respiratory exacerbation in adults with chronic obstructive pulmonary disease (COPD), according to a study of Medicaid claims data.

The data showed that opioid exposure in the prior 7 days was significantly associated with acute respiratory exacerbation. The odds of exacerbation increased as the morphine-equivalent daily dose increased and as the exposure window decreased.

These results “underline the immediacy of the risk of opioid use,” according to Yiran Rong of the department of pharmacy administration at the University of Mississippi in University and colleagues. Ms. Rong and colleagues reported their findings in the American Journal of Epidemiology.

The researchers analyzed Mississippi Medicaid administrative claims data from 2013-2017, which included 1,354 beneficiaries with 1,972 exacerbation events. The beneficiaries had a mean age of 53.11 years, 69.9% were female, and 59.7% were white. The patients had an average of 1.46 exacerbation events, and 62.27% of these events occurred in patients who had an opioid prescription filled in the previous 7 days.

The researchers compared the frequency and dose of opioid exposure in the 7 days before an exacerbation to the opioid exposure in 10 control periods, each 7 days long.

Opioid exposure in the prior 7 days was associated with an 80.8% increase in the odds of exacerbation. The odds ratio, adjusted for exposure to bronchodilators, corticosteroids, benzodiazepines, and beta-blockers, was 1.81 (95% confidence interval, 1.60-2.05).

Opioid exposure was associated with exacerbation in patients with a single exacerbation event (OR, 1.91; 95% CI, 1.61, 2.27), multiple events (OR, 1.71; 95% CI, 1.45-2.01), events recorded in the emergency department (OR, 2.01; 95% CI, 1.71-2.35), and events recorded in the hospital (OR, 1.47; 95% CI, 1.21-1.79).

The odds of exacerbation increased as the morphine-equivalent daily dose increased. Each 25-mg increase in morphine-equivalent daily dose was associated with an 11.2% increase in the odds of exacerbation (OR, 1.11; 95% CI, 1.04-1.20).

“This dose-response relationship is consistent with previously established evidence … and is indicative of the need for caution in prescribing high doses of opioids to COPD patients,” the researchers wrote.

They also found the odds of exacerbation increased as the exposure window decreased. The OR was 1.74 (95% CI, 1.54-1.97) for opioid exposure in an 8-day window before exacerbation and 2.00 (95% CI, 1.73-2.30) for opioid exposure in a 5-day window before exacerbation.

This suggests that “opioid-induced respiratory depression has a very short-term onset,” according to the researchers.

The team noted that this study has limitations, including its retrospective, observational nature, but the results suggest transient opioid use is associated with acute respiratory exacerbation of COPD.

There was no funding for this study, and none of the researchers declared conflicts of interest.

[email protected]

SOURCE: Rong Y et al. Am J Epidemiol. 2019 Jul 30. doi: 10.1093/aje/kwz169.

Occult chronic obstructive pulmonary disease appears to impair right ventricular function for some time before a major cardiovascular event in patients with acute coronary syndromes, data from a clinical trial suggest.

The finding could represent an opportunity for early intervention, Rita Pavasini, MD, wrote in COPD: Journal of Chronic Obstructive Pulmonary Disease.

“Early change of the right ventricular function, as detected by reduced right ventricular strain and reduced fractional area change, is present in [these] patients,” wrote Dr. Pavasini of Azienda Ospedaliero-Universitaria di Ferrara, Cona, Italy. “Further studies are warranted to determine whether these alterations can be reversed or modulated by an early identification and treatment and whether targeting early right ventricular strain reduction results in better clinical outcomes in these comorbid patients.”

Dr. Pavasini and colleagues reported a prespecified subanalysis of the Screening for COPD in ACS Patients (SCAP) trial, which showed that screening patients admitted for acute coronary syndromes with respiratory measures could identify those at risk for undiagnosed COPD. The substudy examined the echocardiographic characteristics of these patients.

SCAP comprised 137 patients who were current or past smokers. At baseline, 29% had a COPD diagnosis. However, most displayed airflow limitation (59% mild, 38% moderate). All underwent transthoracic echocardiogram at baseline and at 6 months.

At baseline, fractional area change (FAC) was already significantly lower in patients with occult COPD than in those without it (38% vs. 44%). Patients with undiagnosed COPD also had significantly reduced right ventricular strain (RVS) (–15 vs. –20).

“Interestingly, the inferior location of myocardial infarction did not influence the results,” the authors said. “Indeed, RVS and FAC did not differ between patients with inferior location of myocardial infarction vs. those without inferior location.”

At 6 months, these differences were unabated. FAC was still significantly lower among those with COPD (37% vs. 46%), and RVS still significantly less (–16 vs. –20). Systolic pulmonary artery pressure (sPAP) was also significantly higher in patients with concomitant COPD (35 vs. 27 mm Hg).

“The early impairment in RVS might reflect the impact of endothelial dysfunction, increased arterial stiffness and inflammation on right heart function, rather than only hypoxia, and even more in a population with mainly mild to moderate COPD,” the team said. “Thus, it is highly probable that sPAP in patients with undiagnosed COPD is mainly determined by concomitant pulmonary disease, which did not differ between acute and chronic phase.”

On the whole, the data suggest that the impairment of right ventricular strain was primarily related to the undiagnosed COPD, and not the cardiovascular event, they said,

“These data are consistent with the observed impairment of RVS and indirectly confirms that undiagnosed COPD determines early changes in the structure and function of the right heart.”

Dr. Pavasini had no relevant financial disclosures.

[email protected]

SOURCE: Pavasini R et al. COPD 2019 Jul 21. doi: 10.1080/15412555.2019.16451059.

Occult chronic obstructive pulmonary disease appears to impair right ventricular function for some time before a major cardiovascular event in patients with acute coronary syndromes, data from a clinical trial suggest.

The finding could represent an opportunity for early intervention, Rita Pavasini, MD, wrote in COPD: Journal of Chronic Obstructive Pulmonary Disease.

“Early change of the right ventricular function, as detected by reduced right ventricular strain and reduced fractional area change, is present in [these] patients,” wrote Dr. Pavasini of Azienda Ospedaliero-Universitaria di Ferrara, Cona, Italy. “Further studies are warranted to determine whether these alterations can be reversed or modulated by an early identification and treatment and whether targeting early right ventricular strain reduction results in better clinical outcomes in these comorbid patients.”

Dr. Pavasini and colleagues reported a prespecified subanalysis of the Screening for COPD in ACS Patients (SCAP) trial, which showed that screening patients admitted for acute coronary syndromes with respiratory measures could identify those at risk for undiagnosed COPD. The substudy examined the echocardiographic characteristics of these patients.

SCAP comprised 137 patients who were current or past smokers. At baseline, 29% had a COPD diagnosis. However, most displayed airflow limitation (59% mild, 38% moderate). All underwent transthoracic echocardiogram at baseline and at 6 months.

At baseline, fractional area change (FAC) was already significantly lower in patients with occult COPD than in those without it (38% vs. 44%). Patients with undiagnosed COPD also had significantly reduced right ventricular strain (RVS) (–15 vs. –20).

“Interestingly, the inferior location of myocardial infarction did not influence the results,” the authors said. “Indeed, RVS and FAC did not differ between patients with inferior location of myocardial infarction vs. those without inferior location.”

At 6 months, these differences were unabated. FAC was still significantly lower among those with COPD (37% vs. 46%), and RVS still significantly less (–16 vs. –20). Systolic pulmonary artery pressure (sPAP) was also significantly higher in patients with concomitant COPD (35 vs. 27 mm Hg).

“The early impairment in RVS might reflect the impact of endothelial dysfunction, increased arterial stiffness and inflammation on right heart function, rather than only hypoxia, and even more in a population with mainly mild to moderate COPD,” the team said. “Thus, it is highly probable that sPAP in patients with undiagnosed COPD is mainly determined by concomitant pulmonary disease, which did not differ between acute and chronic phase.”

On the whole, the data suggest that the impairment of right ventricular strain was primarily related to the undiagnosed COPD, and not the cardiovascular event, they said,

“These data are consistent with the observed impairment of RVS and indirectly confirms that undiagnosed COPD determines early changes in the structure and function of the right heart.”

Dr. Pavasini had no relevant financial disclosures.

[email protected]

SOURCE: Pavasini R et al. COPD 2019 Jul 21. doi: 10.1080/15412555.2019.16451059.

Occult chronic obstructive pulmonary disease appears to impair right ventricular function for some time before a major cardiovascular event in patients with acute coronary syndromes, data from a clinical trial suggest.

The finding could represent an opportunity for early intervention, Rita Pavasini, MD, wrote in COPD: Journal of Chronic Obstructive Pulmonary Disease.

“Early change of the right ventricular function, as detected by reduced right ventricular strain and reduced fractional area change, is present in [these] patients,” wrote Dr. Pavasini of Azienda Ospedaliero-Universitaria di Ferrara, Cona, Italy. “Further studies are warranted to determine whether these alterations can be reversed or modulated by an early identification and treatment and whether targeting early right ventricular strain reduction results in better clinical outcomes in these comorbid patients.”

Dr. Pavasini and colleagues reported a prespecified subanalysis of the Screening for COPD in ACS Patients (SCAP) trial, which showed that screening patients admitted for acute coronary syndromes with respiratory measures could identify those at risk for undiagnosed COPD. The substudy examined the echocardiographic characteristics of these patients.

SCAP comprised 137 patients who were current or past smokers. At baseline, 29% had a COPD diagnosis. However, most displayed airflow limitation (59% mild, 38% moderate). All underwent transthoracic echocardiogram at baseline and at 6 months.

At baseline, fractional area change (FAC) was already significantly lower in patients with occult COPD than in those without it (38% vs. 44%). Patients with undiagnosed COPD also had significantly reduced right ventricular strain (RVS) (–15 vs. –20).

“Interestingly, the inferior location of myocardial infarction did not influence the results,” the authors said. “Indeed, RVS and FAC did not differ between patients with inferior location of myocardial infarction vs. those without inferior location.”

At 6 months, these differences were unabated. FAC was still significantly lower among those with COPD (37% vs. 46%), and RVS still significantly less (–16 vs. –20). Systolic pulmonary artery pressure (sPAP) was also significantly higher in patients with concomitant COPD (35 vs. 27 mm Hg).

“The early impairment in RVS might reflect the impact of endothelial dysfunction, increased arterial stiffness and inflammation on right heart function, rather than only hypoxia, and even more in a population with mainly mild to moderate COPD,” the team said. “Thus, it is highly probable that sPAP in patients with undiagnosed COPD is mainly determined by concomitant pulmonary disease, which did not differ between acute and chronic phase.”

On the whole, the data suggest that the impairment of right ventricular strain was primarily related to the undiagnosed COPD, and not the cardiovascular event, they said,

“These data are consistent with the observed impairment of RVS and indirectly confirms that undiagnosed COPD determines early changes in the structure and function of the right heart.”

Dr. Pavasini had no relevant financial disclosures.

[email protected]

SOURCE: Pavasini R et al. COPD 2019 Jul 21. doi: 10.1080/15412555.2019.16451059.