COPD

Patients with chronic obstructive pulmonary disease (COPD) who are taking benzodiazepines have a more than doubled risk of suicide, compared with similar patients not taking the medications.

The risk of all-cause mortality in COPD patients was not increased with benzodiazepine use, according to the results of research published in the Annals of the American Thoracic Society.

Benzodiazepines were often prescribed for people with COPD to manage chronic symptoms of anxiety, dyspnea, and insomnia that affect quality of life, Lucas M. Donovan, MD, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and his colleagues noted.

However, there were documented concerns that the class of medications could lead to respiratory depression and increase the risk of exacerbations. According to the authors, one particular area of controversy was the long-term use of benzodiazepines, with up to 40% of COPD patients using them on a long-term basis against the advice of clinical guidelines.

They noted that benzodiazepines were also often used to treat dyspnea, a fact which had the potential to introduce confounding into research as the symptom was linked to increased mortality, nonfatal respiratory events, and suicidal ideation.

“One strategy to reduce confounding is to examine risks of benzodiazepines in a sample of patients who are likely to be prescribed benzodiazepines to manage nonrespiratory symptoms, and patients with comorbid posttraumatic stress disorder (PTSD) provide one such opportunity,” they wrote.

In the current study, the research team therefore used data from a nationwide cohort of patients with comorbid COPD and PTSD identified from the Veteran’s Health Administration administrative data between 2010 and 2012. The primary outcome was all-cause mortality in the 2 years following index among propensity-matched veterans with long-term benzodiazepine use, compared with nonusers.

Of 44,555 patients with COPD and PTSD included in the analysis, 29,237 had no benzodiazepine use, 4,782 patients had short-term use (less than 90 days’ supply), and 10,536 patients had long-term use (equal to or more than 90 days).

With a matched sample of 19,552 patients who did not receive benzodiazepines, the risk of all-cause mortality was not significantly different among those with long-term benzodiazepine use relative to those without use (hazard ratio, 1.06; 95% confidence interval, 0.95-1.18).

Furthermore, the specific relative risks of death related to obstructive lung disease and accidental overdose did not differ between the two groups.

Among matched and unmatched patients, short-term benzodiazepine use (HR, 1.16; 95% CI, 1.05-1.28), but not long-term use (HR, 1.03; 95% CI, 0.94-1.13) was associated with increased mortality. However, the authors said it was “worth noting that the associations with short-term use were found in analyses with unmatched patients and may be confounded by the specific episodic reasons for short-term benzodiazepine use such as acute illnesses not captured in our data.”

According to the research team, the most “consistent” and “striking” finding in their analysis was the link between benzodiazepine use and suicide.

They saw a substantially greater risk for death by suicide among those with long-term benzodiazepine use (HR, 2.33; 95% CI, 1.14-4.79). After adjusting all analyses by propensity score for any benzodiazepine exposure, individuals with both short-term and long-term use of benzodiazepines were at a greater risk of suicide (short-term: HR, 2.46; 95% CI, 1.16-5.26; long-term: HR, 2.35; 95% CI, 1.33-4.16).

“Similar to other estimates of the suicide rate within the veteran population (0.3 per 1,000 person-years), the rate of suicide among those without benzodiazepine use (0.4-0.5 per 1,000 person-years) in our sample was greater than the rate in the civilian population (0.1 per 1,000 person-years). However the risk of suicide was substantially greater among those with short- and long-term benzodiazepine use (1.1 per 1,000 person-years),” they wrote.

The use of long-acting benzodiazepines, such as diazepam, chlordiazepoxide, and flurazepam, was also positively associated with suicide (HR for every 10 days of exposure, 1.07; 95% CI, 1.01-1.13), and higher prescribed doses were associated with an increased risk of accidental overdose (HR for every 10 mg of diazepam equivalents, 1.19; 95% CI, 1.07-1.31).

The findings suggested that long-acting agents could pose a particular suicide risk but also “may relate to the sustained half-life of medication or the more severe and sustained mental health symptoms that prompt the use of long-acting agents,” the investigators wrote.

Concomitant opioid use was associated with increased risk of overall mortality (HR for every 10 days of exposure, 1.02; 95% CI, 1.01-1.02) and accidental overdose (HR, 1.11; 95% CI, 1.04-1.18). Individuals with long-term benzodiazepine use also had a higher rate of psychiatric admissions (incidence rate ratio, 1.37; 95% CI, 1.14-1.65).

The researchers concluded that, overall, their results did not suggest that discontinuation of long-term benzodiazepines would reduce overall mortality or death related to obstructive lung disease or overdose.

However, they advised that providers consider discontinuing benzodiazepines in patients already at high suicide risk as well as avoiding the concomitant use of opioids.

“Furthermore, providers should be aware of the risks that new benzodiazepine prescriptions may present to patients with COPD and PTSD without prior exposure to these medications,” they added.

The study was funded by several National Institutes of Heath grants, the ASPIRE (Academic Sleep Pulmonary Integrated Research/Clinical) Fellowship, and a VA grant.

SOURCE: Donovan LM et al. Ann Am Thorac Soc. 2018 Oct 12. doi: 10.1513/AnnalsATS.201802-145OC. Epub ahead of print.

Patients with chronic obstructive pulmonary disease (COPD) who are taking benzodiazepines have a more than doubled risk of suicide, compared with similar patients not taking the medications.

The risk of all-cause mortality in COPD patients was not increased with benzodiazepine use, according to the results of research published in the Annals of the American Thoracic Society.

Benzodiazepines were often prescribed for people with COPD to manage chronic symptoms of anxiety, dyspnea, and insomnia that affect quality of life, Lucas M. Donovan, MD, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and his colleagues noted.

However, there were documented concerns that the class of medications could lead to respiratory depression and increase the risk of exacerbations. According to the authors, one particular area of controversy was the long-term use of benzodiazepines, with up to 40% of COPD patients using them on a long-term basis against the advice of clinical guidelines.

They noted that benzodiazepines were also often used to treat dyspnea, a fact which had the potential to introduce confounding into research as the symptom was linked to increased mortality, nonfatal respiratory events, and suicidal ideation.

“One strategy to reduce confounding is to examine risks of benzodiazepines in a sample of patients who are likely to be prescribed benzodiazepines to manage nonrespiratory symptoms, and patients with comorbid posttraumatic stress disorder (PTSD) provide one such opportunity,” they wrote.

In the current study, the research team therefore used data from a nationwide cohort of patients with comorbid COPD and PTSD identified from the Veteran’s Health Administration administrative data between 2010 and 2012. The primary outcome was all-cause mortality in the 2 years following index among propensity-matched veterans with long-term benzodiazepine use, compared with nonusers.

Of 44,555 patients with COPD and PTSD included in the analysis, 29,237 had no benzodiazepine use, 4,782 patients had short-term use (less than 90 days’ supply), and 10,536 patients had long-term use (equal to or more than 90 days).

With a matched sample of 19,552 patients who did not receive benzodiazepines, the risk of all-cause mortality was not significantly different among those with long-term benzodiazepine use relative to those without use (hazard ratio, 1.06; 95% confidence interval, 0.95-1.18).

Furthermore, the specific relative risks of death related to obstructive lung disease and accidental overdose did not differ between the two groups.

Among matched and unmatched patients, short-term benzodiazepine use (HR, 1.16; 95% CI, 1.05-1.28), but not long-term use (HR, 1.03; 95% CI, 0.94-1.13) was associated with increased mortality. However, the authors said it was “worth noting that the associations with short-term use were found in analyses with unmatched patients and may be confounded by the specific episodic reasons for short-term benzodiazepine use such as acute illnesses not captured in our data.”

According to the research team, the most “consistent” and “striking” finding in their analysis was the link between benzodiazepine use and suicide.

They saw a substantially greater risk for death by suicide among those with long-term benzodiazepine use (HR, 2.33; 95% CI, 1.14-4.79). After adjusting all analyses by propensity score for any benzodiazepine exposure, individuals with both short-term and long-term use of benzodiazepines were at a greater risk of suicide (short-term: HR, 2.46; 95% CI, 1.16-5.26; long-term: HR, 2.35; 95% CI, 1.33-4.16).

“Similar to other estimates of the suicide rate within the veteran population (0.3 per 1,000 person-years), the rate of suicide among those without benzodiazepine use (0.4-0.5 per 1,000 person-years) in our sample was greater than the rate in the civilian population (0.1 per 1,000 person-years). However the risk of suicide was substantially greater among those with short- and long-term benzodiazepine use (1.1 per 1,000 person-years),” they wrote.

The use of long-acting benzodiazepines, such as diazepam, chlordiazepoxide, and flurazepam, was also positively associated with suicide (HR for every 10 days of exposure, 1.07; 95% CI, 1.01-1.13), and higher prescribed doses were associated with an increased risk of accidental overdose (HR for every 10 mg of diazepam equivalents, 1.19; 95% CI, 1.07-1.31).

The findings suggested that long-acting agents could pose a particular suicide risk but also “may relate to the sustained half-life of medication or the more severe and sustained mental health symptoms that prompt the use of long-acting agents,” the investigators wrote.

Concomitant opioid use was associated with increased risk of overall mortality (HR for every 10 days of exposure, 1.02; 95% CI, 1.01-1.02) and accidental overdose (HR, 1.11; 95% CI, 1.04-1.18). Individuals with long-term benzodiazepine use also had a higher rate of psychiatric admissions (incidence rate ratio, 1.37; 95% CI, 1.14-1.65).

The researchers concluded that, overall, their results did not suggest that discontinuation of long-term benzodiazepines would reduce overall mortality or death related to obstructive lung disease or overdose.

However, they advised that providers consider discontinuing benzodiazepines in patients already at high suicide risk as well as avoiding the concomitant use of opioids.

“Furthermore, providers should be aware of the risks that new benzodiazepine prescriptions may present to patients with COPD and PTSD without prior exposure to these medications,” they added.

The study was funded by several National Institutes of Heath grants, the ASPIRE (Academic Sleep Pulmonary Integrated Research/Clinical) Fellowship, and a VA grant.

SOURCE: Donovan LM et al. Ann Am Thorac Soc. 2018 Oct 12. doi: 10.1513/AnnalsATS.201802-145OC. Epub ahead of print.

Patients with chronic obstructive pulmonary disease (COPD) who are taking benzodiazepines have a more than doubled risk of suicide, compared with similar patients not taking the medications.

The risk of all-cause mortality in COPD patients was not increased with benzodiazepine use, according to the results of research published in the Annals of the American Thoracic Society.

Benzodiazepines were often prescribed for people with COPD to manage chronic symptoms of anxiety, dyspnea, and insomnia that affect quality of life, Lucas M. Donovan, MD, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, and his colleagues noted.

However, there were documented concerns that the class of medications could lead to respiratory depression and increase the risk of exacerbations. According to the authors, one particular area of controversy was the long-term use of benzodiazepines, with up to 40% of COPD patients using them on a long-term basis against the advice of clinical guidelines.

They noted that benzodiazepines were also often used to treat dyspnea, a fact which had the potential to introduce confounding into research as the symptom was linked to increased mortality, nonfatal respiratory events, and suicidal ideation.

“One strategy to reduce confounding is to examine risks of benzodiazepines in a sample of patients who are likely to be prescribed benzodiazepines to manage nonrespiratory symptoms, and patients with comorbid posttraumatic stress disorder (PTSD) provide one such opportunity,” they wrote.

In the current study, the research team therefore used data from a nationwide cohort of patients with comorbid COPD and PTSD identified from the Veteran’s Health Administration administrative data between 2010 and 2012. The primary outcome was all-cause mortality in the 2 years following index among propensity-matched veterans with long-term benzodiazepine use, compared with nonusers.

Of 44,555 patients with COPD and PTSD included in the analysis, 29,237 had no benzodiazepine use, 4,782 patients had short-term use (less than 90 days’ supply), and 10,536 patients had long-term use (equal to or more than 90 days).

With a matched sample of 19,552 patients who did not receive benzodiazepines, the risk of all-cause mortality was not significantly different among those with long-term benzodiazepine use relative to those without use (hazard ratio, 1.06; 95% confidence interval, 0.95-1.18).

Furthermore, the specific relative risks of death related to obstructive lung disease and accidental overdose did not differ between the two groups.

Among matched and unmatched patients, short-term benzodiazepine use (HR, 1.16; 95% CI, 1.05-1.28), but not long-term use (HR, 1.03; 95% CI, 0.94-1.13) was associated with increased mortality. However, the authors said it was “worth noting that the associations with short-term use were found in analyses with unmatched patients and may be confounded by the specific episodic reasons for short-term benzodiazepine use such as acute illnesses not captured in our data.”

According to the research team, the most “consistent” and “striking” finding in their analysis was the link between benzodiazepine use and suicide.

They saw a substantially greater risk for death by suicide among those with long-term benzodiazepine use (HR, 2.33; 95% CI, 1.14-4.79). After adjusting all analyses by propensity score for any benzodiazepine exposure, individuals with both short-term and long-term use of benzodiazepines were at a greater risk of suicide (short-term: HR, 2.46; 95% CI, 1.16-5.26; long-term: HR, 2.35; 95% CI, 1.33-4.16).

“Similar to other estimates of the suicide rate within the veteran population (0.3 per 1,000 person-years), the rate of suicide among those without benzodiazepine use (0.4-0.5 per 1,000 person-years) in our sample was greater than the rate in the civilian population (0.1 per 1,000 person-years). However the risk of suicide was substantially greater among those with short- and long-term benzodiazepine use (1.1 per 1,000 person-years),” they wrote.

The use of long-acting benzodiazepines, such as diazepam, chlordiazepoxide, and flurazepam, was also positively associated with suicide (HR for every 10 days of exposure, 1.07; 95% CI, 1.01-1.13), and higher prescribed doses were associated with an increased risk of accidental overdose (HR for every 10 mg of diazepam equivalents, 1.19; 95% CI, 1.07-1.31).

The findings suggested that long-acting agents could pose a particular suicide risk but also “may relate to the sustained half-life of medication or the more severe and sustained mental health symptoms that prompt the use of long-acting agents,” the investigators wrote.

Concomitant opioid use was associated with increased risk of overall mortality (HR for every 10 days of exposure, 1.02; 95% CI, 1.01-1.02) and accidental overdose (HR, 1.11; 95% CI, 1.04-1.18). Individuals with long-term benzodiazepine use also had a higher rate of psychiatric admissions (incidence rate ratio, 1.37; 95% CI, 1.14-1.65).

The researchers concluded that, overall, their results did not suggest that discontinuation of long-term benzodiazepines would reduce overall mortality or death related to obstructive lung disease or overdose.

However, they advised that providers consider discontinuing benzodiazepines in patients already at high suicide risk as well as avoiding the concomitant use of opioids.

“Furthermore, providers should be aware of the risks that new benzodiazepine prescriptions may present to patients with COPD and PTSD without prior exposure to these medications,” they added.

The study was funded by several National Institutes of Heath grants, the ASPIRE (Academic Sleep Pulmonary Integrated Research/Clinical) Fellowship, and a VA grant.

SOURCE: Donovan LM et al. Ann Am Thorac Soc. 2018 Oct 12. doi: 10.1513/AnnalsATS.201802-145OC. Epub ahead of print.

https://www.medscape.com/viewarticle/902668?src=par_chest_stm_mscpedt&faf=1

https://www.medscape.com/viewarticle/902668?src=par_chest_stm_mscpedt&faf=1

https://www.medscape.com/viewarticle/902668?src=par_chest_stm_mscpedt&faf=1

SAN ANTONIO – COPD patients with pulmonary circulation disorders were more than four times as likely to need invasive ventilation after noninvasive ventilation (NIV) failed for acute exacerbations, found a new study.

Tara Haelle/MDedge News

Patients with fluid and electrolyte abnormalities or alcohol abuse also had a greater risk of escalating beyond NIV for exacerbations, according to the findings.

“Patients with these underlying conditions should be monitored closely, especially individuals with existing pulmonary disorders as they are at highest risk,” Di Pan, DO, of Mount Sinai Hospital, New York, reported at annual meeting of the American College of Chest Physicians.

The researchers used the 2012-2014 Nationwide Inpatient Sample database to retrospectively analyze data from 73,480 patients, average age 67.8 years, who had a primary diagnosis of COPD exacerbation and who had received initial treatment with NIV in their first 24 hours after hospitalization. The report is in CHEST^® Journal(2018 Oct. doi: 10.1016/j.chest.2018.08.340).

The researchers examined associations between NIV failure and 29 Elixhauser comorbidity measures to identify what clinical characteristics might predict the need for invasive ventilation. They defined NIV failure as requiring intubation at any time within 30 days of admission.

Pulmonary circulation disorders emerged as the strongest predictor of the need for intubation, with a fourfold increase in relative risk (hazard ratio [HR]: 4.19, P less than .001). Alcohol abuse (HR: 1.85, P = .01) and fluid and electrolyte abnormalities (HR: 1.3, P less than .001) followed as additional factors associated with NIV failure. The latter included irregularities in potassium or sodium, acid-base disorders, hypervolemia and hypovolemia.

Among the 3,740 patients with alcohol abuse, additional statistically significant associations with intubation included a slightly higher mean age, female sex, and the mean Charlson comorbidity index. Mean age of those requiring intubation in this group was 62.28 years, compared 61.47 years among those in whom NIV was adequate (P = .03). Among those intubated, 30.2% of the patients were female, compared with 26.3% female patients in the nonintubated group.

Among the 26,150 patients with fluid, electrolyte and acid-base disturbances, younger patients were more likely to require intubation: The average age of those needing intubation was 67.23 years, compared with 69.3 years for those non-intubated (P less than .001). While a higher Charlson index (2.83 vs. 2.53) was again correlated with greater risk of needing intubation (P less than .001), males were now more likely to require intubation: 58.1% of those without intubation were female, compared with 53.9% of those needing intubation (P less than .001).

Within the 890 patients with pulmonary circulation disorders, mean age was 68.03 years for intubation and 70.77 years for nonintubation (P less than .001). In this group, 56.4% of the patients requiring intubation were female, compared to 47.9% of patients not intubated. The average Charlson index was lower (3.11) among those requiring intubation than among those not needing it (3.57, P less than .001).

The findings were limited by the lack of disease severity stratification and use of now-outdated ICD-9 coding. The researchers also lacked detailed clinical data, such as lab values, imaging results, and vital signs, and Dr. Pan acknowledged the broad variation within the diagnoses of the also-broad Elixhauser comorbidity index.

“For the next steps, we can do a stratified analysis” to identify which specific pulmonary circulation diseases primarily account for the association with intubation, Dr. Pan said.

No external funding was noted. The authors reported having no disclosures.

SOURCE: Pan D. et al. CHEST 2018. https://doi.org/10.1016/j.chest.2018.08.340.

SAN ANTONIO – COPD patients with pulmonary circulation disorders were more than four times as likely to need invasive ventilation after noninvasive ventilation (NIV) failed for acute exacerbations, found a new study.

Tara Haelle/MDedge News

Patients with fluid and electrolyte abnormalities or alcohol abuse also had a greater risk of escalating beyond NIV for exacerbations, according to the findings.

“Patients with these underlying conditions should be monitored closely, especially individuals with existing pulmonary disorders as they are at highest risk,” Di Pan, DO, of Mount Sinai Hospital, New York, reported at annual meeting of the American College of Chest Physicians.

The researchers used the 2012-2014 Nationwide Inpatient Sample database to retrospectively analyze data from 73,480 patients, average age 67.8 years, who had a primary diagnosis of COPD exacerbation and who had received initial treatment with NIV in their first 24 hours after hospitalization. The report is in CHEST^® Journal(2018 Oct. doi: 10.1016/j.chest.2018.08.340).

The researchers examined associations between NIV failure and 29 Elixhauser comorbidity measures to identify what clinical characteristics might predict the need for invasive ventilation. They defined NIV failure as requiring intubation at any time within 30 days of admission.

Pulmonary circulation disorders emerged as the strongest predictor of the need for intubation, with a fourfold increase in relative risk (hazard ratio [HR]: 4.19, P less than .001). Alcohol abuse (HR: 1.85, P = .01) and fluid and electrolyte abnormalities (HR: 1.3, P less than .001) followed as additional factors associated with NIV failure. The latter included irregularities in potassium or sodium, acid-base disorders, hypervolemia and hypovolemia.

Among the 3,740 patients with alcohol abuse, additional statistically significant associations with intubation included a slightly higher mean age, female sex, and the mean Charlson comorbidity index. Mean age of those requiring intubation in this group was 62.28 years, compared 61.47 years among those in whom NIV was adequate (P = .03). Among those intubated, 30.2% of the patients were female, compared with 26.3% female patients in the nonintubated group.

Among the 26,150 patients with fluid, electrolyte and acid-base disturbances, younger patients were more likely to require intubation: The average age of those needing intubation was 67.23 years, compared with 69.3 years for those non-intubated (P less than .001). While a higher Charlson index (2.83 vs. 2.53) was again correlated with greater risk of needing intubation (P less than .001), males were now more likely to require intubation: 58.1% of those without intubation were female, compared with 53.9% of those needing intubation (P less than .001).

Within the 890 patients with pulmonary circulation disorders, mean age was 68.03 years for intubation and 70.77 years for nonintubation (P less than .001). In this group, 56.4% of the patients requiring intubation were female, compared to 47.9% of patients not intubated. The average Charlson index was lower (3.11) among those requiring intubation than among those not needing it (3.57, P less than .001).

The findings were limited by the lack of disease severity stratification and use of now-outdated ICD-9 coding. The researchers also lacked detailed clinical data, such as lab values, imaging results, and vital signs, and Dr. Pan acknowledged the broad variation within the diagnoses of the also-broad Elixhauser comorbidity index.

“For the next steps, we can do a stratified analysis” to identify which specific pulmonary circulation diseases primarily account for the association with intubation, Dr. Pan said.

No external funding was noted. The authors reported having no disclosures.

SOURCE: Pan D. et al. CHEST 2018. https://doi.org/10.1016/j.chest.2018.08.340.

SAN ANTONIO – COPD patients with pulmonary circulation disorders were more than four times as likely to need invasive ventilation after noninvasive ventilation (NIV) failed for acute exacerbations, found a new study.

Tara Haelle/MDedge News

Patients with fluid and electrolyte abnormalities or alcohol abuse also had a greater risk of escalating beyond NIV for exacerbations, according to the findings.

“Patients with these underlying conditions should be monitored closely, especially individuals with existing pulmonary disorders as they are at highest risk,” Di Pan, DO, of Mount Sinai Hospital, New York, reported at annual meeting of the American College of Chest Physicians.

The researchers used the 2012-2014 Nationwide Inpatient Sample database to retrospectively analyze data from 73,480 patients, average age 67.8 years, who had a primary diagnosis of COPD exacerbation and who had received initial treatment with NIV in their first 24 hours after hospitalization. The report is in CHEST^® Journal(2018 Oct. doi: 10.1016/j.chest.2018.08.340).

The researchers examined associations between NIV failure and 29 Elixhauser comorbidity measures to identify what clinical characteristics might predict the need for invasive ventilation. They defined NIV failure as requiring intubation at any time within 30 days of admission.

Pulmonary circulation disorders emerged as the strongest predictor of the need for intubation, with a fourfold increase in relative risk (hazard ratio [HR]: 4.19, P less than .001). Alcohol abuse (HR: 1.85, P = .01) and fluid and electrolyte abnormalities (HR: 1.3, P less than .001) followed as additional factors associated with NIV failure. The latter included irregularities in potassium or sodium, acid-base disorders, hypervolemia and hypovolemia.

Among the 3,740 patients with alcohol abuse, additional statistically significant associations with intubation included a slightly higher mean age, female sex, and the mean Charlson comorbidity index. Mean age of those requiring intubation in this group was 62.28 years, compared 61.47 years among those in whom NIV was adequate (P = .03). Among those intubated, 30.2% of the patients were female, compared with 26.3% female patients in the nonintubated group.

Among the 26,150 patients with fluid, electrolyte and acid-base disturbances, younger patients were more likely to require intubation: The average age of those needing intubation was 67.23 years, compared with 69.3 years for those non-intubated (P less than .001). While a higher Charlson index (2.83 vs. 2.53) was again correlated with greater risk of needing intubation (P less than .001), males were now more likely to require intubation: 58.1% of those without intubation were female, compared with 53.9% of those needing intubation (P less than .001).

Within the 890 patients with pulmonary circulation disorders, mean age was 68.03 years for intubation and 70.77 years for nonintubation (P less than .001). In this group, 56.4% of the patients requiring intubation were female, compared to 47.9% of patients not intubated. The average Charlson index was lower (3.11) among those requiring intubation than among those not needing it (3.57, P less than .001).

The findings were limited by the lack of disease severity stratification and use of now-outdated ICD-9 coding. The researchers also lacked detailed clinical data, such as lab values, imaging results, and vital signs, and Dr. Pan acknowledged the broad variation within the diagnoses of the also-broad Elixhauser comorbidity index.

“For the next steps, we can do a stratified analysis” to identify which specific pulmonary circulation diseases primarily account for the association with intubation, Dr. Pan said.

No external funding was noted. The authors reported having no disclosures.

SOURCE: Pan D. et al. CHEST 2018. https://doi.org/10.1016/j.chest.2018.08.340.

SAN ANTONIO – Interventions that address variations in inflammation type and metabolism unique to obese patients with asthma or COPD might prove useful for improving their management, Cherry Wongtrakool, MD, of Emory University, Atlanta, said in a presentation at the annual meeting of the American College of Chest Physicians.

Obese patients with asthma or COPD typically have metabolic and inflammatory profiles that differ from those of nonobese patients with the disorders. Obesity is associated with the development of asthma as well as its severity and the risk for exacerbations. Obese patients with asthma are less likely to have controlled disease or to respond to medication.

The variations in asthma related to obesity even can be traced to infancy for some. Children with rapid weight gain after birth, for example, have an increased risk for developing asthma. In the recently published Boston Birth Cohort study, more than 500 babies from urban, low income families were followed from birth until age 16. Babies with rapid weight gain at 4 months and at 24 months had an increased risk for developing asthma by age 16. Even after adjusting for multiple risk factors, the increased risk for developing asthma persisted in these obese infants.

Higher BMIs during infancy may affect lung development, which continues up to age 5-8 years, Dr. Wongtrakool said. Obesity may affect immune system development. Asthma may develop when persistent inflammation during infancy gets a second hit from genetic factors or from risk factors such as atopy or maternal smoking.

Dr. Wongtrakool noted that obese patients with asthma, unlike nonobese asthma patients, tend to have non-TH2 inflammation. Their TH1/TH2 ratio in stimulated T cells is higher and is directly associated with insulin resistance. Similar to obese patients without asthma, they have higher levels of circulating TNF-alpha, interferon-gamma inducible protein 10, and monocyte chemoattractant protein-1 (MCP-1). They are more likely to have insulin resistance, low high-density lipid levels, differences in gut microbiota, increased leptin, decreased adiponectin, increased asymmetric dimethylarginine, and decreased exhaled nitrous oxide (NO).

In broncheoalveolar lavage samples, obese asthma patients have more cells that secrete interleukin-17, Dr. Wontrakool said. TH17-associated inflammation also has an influence in asthma with obesity. A recent study of 30 obese and lean asthma patients found a difference in metabolites measured in breath samples of obese people with asthma, compared with lean people with asthma and obese people without asthma.

In terms of metabolites in their breath, obese asthma patients clustered together and differed from lean patients with asthma and obese patients without asthma.

Obese people with asthma also differ in their gut microbiota, having more firmicutes species and decreased bacteroides species. Studies in mice indicate that these species have a role in body weight and that altering gut microbiota via fecal transplant was associated with weight loss when obese mice received fecal transplants from lean mice, and vice versa.

In the Supplemental Nutrition in Asthma Control (SNAC) study, preadolescents with asthma were given a nutrition bar designed by researchers at the Children’s Hospital Oakland (Calif.) Research Institute. The children also received asthma education and exercise classes, but the intervention was not designed to reduce weight. FVC and FEV₁ improved in all study participants, but those participants in the low inflammation subgroup had the most pronounced improvements in FVC and FEV₁ after 2 months.

Dr. Wongtrakool called the study “intriguing,” as it indicates asthma patients with lower level inflammation appear more likely to benefit from nutritional supplementation.

In another study of 55 obese adult asthma patients, a hypocaloric diet, access to a nutritionist and psychologist, and exercise classes were associated with improved asthma control and an improved inflammatory and metabolic profile.

In a British registry of the outcomes of bariatric surgery for obesity, patients who also had asthma had a decrease in asthma prevalence in the year after surgery that persisted over 5 years.

The association of COPD with obesity has been less studied than asthma and COPD, but metabolic syndrome appears to be on the rise in these patients. In a study performed over a decade ago, 47% of COPD patients met the definition of metabolic syndrome; a more recent study found 77% of COPD patients met the standard.

Admission glucose levels also have been found to influence the severity of COPD exacerbation. With higher blood glucose levels, there was a higher risk of mortality—from 12% in those with glucose levels of less than 6.0 mmol/l to 31% among those with glucose levels exceeding 9.0 mmol/l, one study showed.

Bariatric surgery may reduce the risk of acute exacerbations of COPD in obese patients, another recent study found. In a study of 480 obese patients with COPD who underwent bariatric surgery, their 28% presurgical risk of acute exacerbations of COPD was cut in half by 12 months after surgery, and the reduction persisted at 24 months.

SAN ANTONIO – Interventions that address variations in inflammation type and metabolism unique to obese patients with asthma or COPD might prove useful for improving their management, Cherry Wongtrakool, MD, of Emory University, Atlanta, said in a presentation at the annual meeting of the American College of Chest Physicians.

Obese patients with asthma or COPD typically have metabolic and inflammatory profiles that differ from those of nonobese patients with the disorders. Obesity is associated with the development of asthma as well as its severity and the risk for exacerbations. Obese patients with asthma are less likely to have controlled disease or to respond to medication.

The variations in asthma related to obesity even can be traced to infancy for some. Children with rapid weight gain after birth, for example, have an increased risk for developing asthma. In the recently published Boston Birth Cohort study, more than 500 babies from urban, low income families were followed from birth until age 16. Babies with rapid weight gain at 4 months and at 24 months had an increased risk for developing asthma by age 16. Even after adjusting for multiple risk factors, the increased risk for developing asthma persisted in these obese infants.

Higher BMIs during infancy may affect lung development, which continues up to age 5-8 years, Dr. Wongtrakool said. Obesity may affect immune system development. Asthma may develop when persistent inflammation during infancy gets a second hit from genetic factors or from risk factors such as atopy or maternal smoking.

Dr. Wongtrakool noted that obese patients with asthma, unlike nonobese asthma patients, tend to have non-TH2 inflammation. Their TH1/TH2 ratio in stimulated T cells is higher and is directly associated with insulin resistance. Similar to obese patients without asthma, they have higher levels of circulating TNF-alpha, interferon-gamma inducible protein 10, and monocyte chemoattractant protein-1 (MCP-1). They are more likely to have insulin resistance, low high-density lipid levels, differences in gut microbiota, increased leptin, decreased adiponectin, increased asymmetric dimethylarginine, and decreased exhaled nitrous oxide (NO).

In broncheoalveolar lavage samples, obese asthma patients have more cells that secrete interleukin-17, Dr. Wontrakool said. TH17-associated inflammation also has an influence in asthma with obesity. A recent study of 30 obese and lean asthma patients found a difference in metabolites measured in breath samples of obese people with asthma, compared with lean people with asthma and obese people without asthma.

In terms of metabolites in their breath, obese asthma patients clustered together and differed from lean patients with asthma and obese patients without asthma.

Obese people with asthma also differ in their gut microbiota, having more firmicutes species and decreased bacteroides species. Studies in mice indicate that these species have a role in body weight and that altering gut microbiota via fecal transplant was associated with weight loss when obese mice received fecal transplants from lean mice, and vice versa.

In the Supplemental Nutrition in Asthma Control (SNAC) study, preadolescents with asthma were given a nutrition bar designed by researchers at the Children’s Hospital Oakland (Calif.) Research Institute. The children also received asthma education and exercise classes, but the intervention was not designed to reduce weight. FVC and FEV₁ improved in all study participants, but those participants in the low inflammation subgroup had the most pronounced improvements in FVC and FEV₁ after 2 months.

Dr. Wongtrakool called the study “intriguing,” as it indicates asthma patients with lower level inflammation appear more likely to benefit from nutritional supplementation.

In another study of 55 obese adult asthma patients, a hypocaloric diet, access to a nutritionist and psychologist, and exercise classes were associated with improved asthma control and an improved inflammatory and metabolic profile.

In a British registry of the outcomes of bariatric surgery for obesity, patients who also had asthma had a decrease in asthma prevalence in the year after surgery that persisted over 5 years.

The association of COPD with obesity has been less studied than asthma and COPD, but metabolic syndrome appears to be on the rise in these patients. In a study performed over a decade ago, 47% of COPD patients met the definition of metabolic syndrome; a more recent study found 77% of COPD patients met the standard.

Admission glucose levels also have been found to influence the severity of COPD exacerbation. With higher blood glucose levels, there was a higher risk of mortality—from 12% in those with glucose levels of less than 6.0 mmol/l to 31% among those with glucose levels exceeding 9.0 mmol/l, one study showed.

Bariatric surgery may reduce the risk of acute exacerbations of COPD in obese patients, another recent study found. In a study of 480 obese patients with COPD who underwent bariatric surgery, their 28% presurgical risk of acute exacerbations of COPD was cut in half by 12 months after surgery, and the reduction persisted at 24 months.

SAN ANTONIO – Interventions that address variations in inflammation type and metabolism unique to obese patients with asthma or COPD might prove useful for improving their management, Cherry Wongtrakool, MD, of Emory University, Atlanta, said in a presentation at the annual meeting of the American College of Chest Physicians.

Obese patients with asthma or COPD typically have metabolic and inflammatory profiles that differ from those of nonobese patients with the disorders. Obesity is associated with the development of asthma as well as its severity and the risk for exacerbations. Obese patients with asthma are less likely to have controlled disease or to respond to medication.

The variations in asthma related to obesity even can be traced to infancy for some. Children with rapid weight gain after birth, for example, have an increased risk for developing asthma. In the recently published Boston Birth Cohort study, more than 500 babies from urban, low income families were followed from birth until age 16. Babies with rapid weight gain at 4 months and at 24 months had an increased risk for developing asthma by age 16. Even after adjusting for multiple risk factors, the increased risk for developing asthma persisted in these obese infants.

Higher BMIs during infancy may affect lung development, which continues up to age 5-8 years, Dr. Wongtrakool said. Obesity may affect immune system development. Asthma may develop when persistent inflammation during infancy gets a second hit from genetic factors or from risk factors such as atopy or maternal smoking.

Dr. Wongtrakool noted that obese patients with asthma, unlike nonobese asthma patients, tend to have non-TH2 inflammation. Their TH1/TH2 ratio in stimulated T cells is higher and is directly associated with insulin resistance. Similar to obese patients without asthma, they have higher levels of circulating TNF-alpha, interferon-gamma inducible protein 10, and monocyte chemoattractant protein-1 (MCP-1). They are more likely to have insulin resistance, low high-density lipid levels, differences in gut microbiota, increased leptin, decreased adiponectin, increased asymmetric dimethylarginine, and decreased exhaled nitrous oxide (NO).

In broncheoalveolar lavage samples, obese asthma patients have more cells that secrete interleukin-17, Dr. Wontrakool said. TH17-associated inflammation also has an influence in asthma with obesity. A recent study of 30 obese and lean asthma patients found a difference in metabolites measured in breath samples of obese people with asthma, compared with lean people with asthma and obese people without asthma.

In terms of metabolites in their breath, obese asthma patients clustered together and differed from lean patients with asthma and obese patients without asthma.

Obese people with asthma also differ in their gut microbiota, having more firmicutes species and decreased bacteroides species. Studies in mice indicate that these species have a role in body weight and that altering gut microbiota via fecal transplant was associated with weight loss when obese mice received fecal transplants from lean mice, and vice versa.

In the Supplemental Nutrition in Asthma Control (SNAC) study, preadolescents with asthma were given a nutrition bar designed by researchers at the Children’s Hospital Oakland (Calif.) Research Institute. The children also received asthma education and exercise classes, but the intervention was not designed to reduce weight. FVC and FEV₁ improved in all study participants, but those participants in the low inflammation subgroup had the most pronounced improvements in FVC and FEV₁ after 2 months.

Dr. Wongtrakool called the study “intriguing,” as it indicates asthma patients with lower level inflammation appear more likely to benefit from nutritional supplementation.

In another study of 55 obese adult asthma patients, a hypocaloric diet, access to a nutritionist and psychologist, and exercise classes were associated with improved asthma control and an improved inflammatory and metabolic profile.

In a British registry of the outcomes of bariatric surgery for obesity, patients who also had asthma had a decrease in asthma prevalence in the year after surgery that persisted over 5 years.

The association of COPD with obesity has been less studied than asthma and COPD, but metabolic syndrome appears to be on the rise in these patients. In a study performed over a decade ago, 47% of COPD patients met the definition of metabolic syndrome; a more recent study found 77% of COPD patients met the standard.

Admission glucose levels also have been found to influence the severity of COPD exacerbation. With higher blood glucose levels, there was a higher risk of mortality—from 12% in those with glucose levels of less than 6.0 mmol/l to 31% among those with glucose levels exceeding 9.0 mmol/l, one study showed.

Bariatric surgery may reduce the risk of acute exacerbations of COPD in obese patients, another recent study found. In a study of 480 obese patients with COPD who underwent bariatric surgery, their 28% presurgical risk of acute exacerbations of COPD was cut in half by 12 months after surgery, and the reduction persisted at 24 months.

PARIS – In a sham-controlled randomized trial that enrolled patients with moderate to severe chronic obstructive pulmonary disease (COPD), targeted lung denervation (TLD) was not only found safe, which was the primary goal of the study, but effective, according to data presented at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

Within the first year of follow-up, “the positive benefit in those randomized to TLD persisted with a more than 50% reduction in the number of patients hospitalized for respiratory complications,” reported Dirk-Jan Slebos, MD, department of lung diseases and tuberculosis, University of Gröningen, the Netherlands.

In this phase 2 trial, called AIRFLOW-2, 82 patients were randomized to receive TLD, which ablates nerves with radiofrequency energy, or a sham procedure. The study enrolled patients with moderate to severe COPD and forced expiratory volume in 1 second of 30%-60% predicted. All patients were treated with the long-acting muscarinic antagonist (LAMA) tiotropium.

The primary endpoint was a composite of respiratory-related adverse events, such as respiratory failure, worsening bronchitis, or worsening dyspnea. Secondary endpoints included serious adverse events of any kind as well as a variety of measures of efficacy, including changes in quality of life as measured with standardized tools such as the St. George’s Respiratory Questionnaire (SGRQ).

Within 6 months of the procedure, 71% of those randomized to the sham procedure and 32% of those treated with TLD experienced one of the predefined respiratory adverse events (P = .0008). At 1 year, 25% of patients in the sham group versus 12% in the TLD group were hospitalized for an exacerbation (P = .039). In addition to achieving greater improvement in several of the individual symptoms, such as dyspnea, those randomized to TLD also achieved numerical improvements in SGRQ scores (–8.3 vs. –3.8) at 12 months.

Gastrointestinal adverse events were more common in the TLD group (15% vs. 5%). Although the higher rate of GI events, which included nausea, bloating, and abdominal discomfort, did not reach statistical significance, it was attributed to off-target exposure of nerves in the GI system to the radiofrequency energy.

“We are improving our imaging process in order to implement additional measures to avoid these nerves,” said Dr. Slebos, who added that this potential risk can be modified. In this study, all of the GI symptoms resolved.

Dr. Slebos emphasized that the 12-month follow-up permitted the study to “confirm that TLD is safe and technically feasible with no late-onset safety signals.” It has set the stage for AIRFLOW-3, a phase 3 trial that is expected to lead to regulatory approval of the catheter if it shows similar safety and efficacy.

The principle of TLD is to deliver energy to ablate parasympathetic pulmonary nerves. The exact mechanism of benefit has not been proved, but it is believed that inhibiting release of acetylcholine that induces smooth muscle constriction has several beneficial downstream effects, including prevention of hyperinflation and reduced mucus production. AIRFLOW-3, like AIRFLOW-2, will evaluate a proprietary catheter developed for this purpose.

“TLD will not replace pharmaceutical therapy. Rather, it appears to have a synergistic effect,” explained Dr. Slebos, who said the procedure is performed on an outpatient basis. The average procedure time for TLD in AIRFLOW-2 was 42 minutes.

The first human study of TLD, also led by Dr. Slebos, was published in 2015. While several subsequent patient series support efficacy and benefit, Daiana Stolz, MD, Clinic for Respiratory Medicine and Pulmonary Cell Research, University of Basel (Switzerland), called the data from this sham-controlled trial “really exciting and important.” However, she said, the larger AIRFLOW-3 trial is needed “to confirm this is an effective and safe treatment.”
 

Dr. Slebos receives consultancy fees from Aeris Therapeutics, Boston Scientific, Broncus Technologies, CSA Medical. Olympus, Portaero, PulmonX, PneumRx/BTG, and Nuvaira, which provided the funding for this study.

PARIS – In a sham-controlled randomized trial that enrolled patients with moderate to severe chronic obstructive pulmonary disease (COPD), targeted lung denervation (TLD) was not only found safe, which was the primary goal of the study, but effective, according to data presented at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

Within the first year of follow-up, “the positive benefit in those randomized to TLD persisted with a more than 50% reduction in the number of patients hospitalized for respiratory complications,” reported Dirk-Jan Slebos, MD, department of lung diseases and tuberculosis, University of Gröningen, the Netherlands.

In this phase 2 trial, called AIRFLOW-2, 82 patients were randomized to receive TLD, which ablates nerves with radiofrequency energy, or a sham procedure. The study enrolled patients with moderate to severe COPD and forced expiratory volume in 1 second of 30%-60% predicted. All patients were treated with the long-acting muscarinic antagonist (LAMA) tiotropium.

The primary endpoint was a composite of respiratory-related adverse events, such as respiratory failure, worsening bronchitis, or worsening dyspnea. Secondary endpoints included serious adverse events of any kind as well as a variety of measures of efficacy, including changes in quality of life as measured with standardized tools such as the St. George’s Respiratory Questionnaire (SGRQ).

Within 6 months of the procedure, 71% of those randomized to the sham procedure and 32% of those treated with TLD experienced one of the predefined respiratory adverse events (P = .0008). At 1 year, 25% of patients in the sham group versus 12% in the TLD group were hospitalized for an exacerbation (P = .039). In addition to achieving greater improvement in several of the individual symptoms, such as dyspnea, those randomized to TLD also achieved numerical improvements in SGRQ scores (–8.3 vs. –3.8) at 12 months.

Gastrointestinal adverse events were more common in the TLD group (15% vs. 5%). Although the higher rate of GI events, which included nausea, bloating, and abdominal discomfort, did not reach statistical significance, it was attributed to off-target exposure of nerves in the GI system to the radiofrequency energy.

“We are improving our imaging process in order to implement additional measures to avoid these nerves,” said Dr. Slebos, who added that this potential risk can be modified. In this study, all of the GI symptoms resolved.

Dr. Slebos emphasized that the 12-month follow-up permitted the study to “confirm that TLD is safe and technically feasible with no late-onset safety signals.” It has set the stage for AIRFLOW-3, a phase 3 trial that is expected to lead to regulatory approval of the catheter if it shows similar safety and efficacy.

The principle of TLD is to deliver energy to ablate parasympathetic pulmonary nerves. The exact mechanism of benefit has not been proved, but it is believed that inhibiting release of acetylcholine that induces smooth muscle constriction has several beneficial downstream effects, including prevention of hyperinflation and reduced mucus production. AIRFLOW-3, like AIRFLOW-2, will evaluate a proprietary catheter developed for this purpose.

“TLD will not replace pharmaceutical therapy. Rather, it appears to have a synergistic effect,” explained Dr. Slebos, who said the procedure is performed on an outpatient basis. The average procedure time for TLD in AIRFLOW-2 was 42 minutes.

The first human study of TLD, also led by Dr. Slebos, was published in 2015. While several subsequent patient series support efficacy and benefit, Daiana Stolz, MD, Clinic for Respiratory Medicine and Pulmonary Cell Research, University of Basel (Switzerland), called the data from this sham-controlled trial “really exciting and important.” However, she said, the larger AIRFLOW-3 trial is needed “to confirm this is an effective and safe treatment.”
 

Dr. Slebos receives consultancy fees from Aeris Therapeutics, Boston Scientific, Broncus Technologies, CSA Medical. Olympus, Portaero, PulmonX, PneumRx/BTG, and Nuvaira, which provided the funding for this study.

PARIS – In a sham-controlled randomized trial that enrolled patients with moderate to severe chronic obstructive pulmonary disease (COPD), targeted lung denervation (TLD) was not only found safe, which was the primary goal of the study, but effective, according to data presented at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

Within the first year of follow-up, “the positive benefit in those randomized to TLD persisted with a more than 50% reduction in the number of patients hospitalized for respiratory complications,” reported Dirk-Jan Slebos, MD, department of lung diseases and tuberculosis, University of Gröningen, the Netherlands.

In this phase 2 trial, called AIRFLOW-2, 82 patients were randomized to receive TLD, which ablates nerves with radiofrequency energy, or a sham procedure. The study enrolled patients with moderate to severe COPD and forced expiratory volume in 1 second of 30%-60% predicted. All patients were treated with the long-acting muscarinic antagonist (LAMA) tiotropium.

The primary endpoint was a composite of respiratory-related adverse events, such as respiratory failure, worsening bronchitis, or worsening dyspnea. Secondary endpoints included serious adverse events of any kind as well as a variety of measures of efficacy, including changes in quality of life as measured with standardized tools such as the St. George’s Respiratory Questionnaire (SGRQ).

Within 6 months of the procedure, 71% of those randomized to the sham procedure and 32% of those treated with TLD experienced one of the predefined respiratory adverse events (P = .0008). At 1 year, 25% of patients in the sham group versus 12% in the TLD group were hospitalized for an exacerbation (P = .039). In addition to achieving greater improvement in several of the individual symptoms, such as dyspnea, those randomized to TLD also achieved numerical improvements in SGRQ scores (–8.3 vs. –3.8) at 12 months.

Gastrointestinal adverse events were more common in the TLD group (15% vs. 5%). Although the higher rate of GI events, which included nausea, bloating, and abdominal discomfort, did not reach statistical significance, it was attributed to off-target exposure of nerves in the GI system to the radiofrequency energy.

“We are improving our imaging process in order to implement additional measures to avoid these nerves,” said Dr. Slebos, who added that this potential risk can be modified. In this study, all of the GI symptoms resolved.

Dr. Slebos emphasized that the 12-month follow-up permitted the study to “confirm that TLD is safe and technically feasible with no late-onset safety signals.” It has set the stage for AIRFLOW-3, a phase 3 trial that is expected to lead to regulatory approval of the catheter if it shows similar safety and efficacy.

The principle of TLD is to deliver energy to ablate parasympathetic pulmonary nerves. The exact mechanism of benefit has not been proved, but it is believed that inhibiting release of acetylcholine that induces smooth muscle constriction has several beneficial downstream effects, including prevention of hyperinflation and reduced mucus production. AIRFLOW-3, like AIRFLOW-2, will evaluate a proprietary catheter developed for this purpose.

“TLD will not replace pharmaceutical therapy. Rather, it appears to have a synergistic effect,” explained Dr. Slebos, who said the procedure is performed on an outpatient basis. The average procedure time for TLD in AIRFLOW-2 was 42 minutes.

The first human study of TLD, also led by Dr. Slebos, was published in 2015. While several subsequent patient series support efficacy and benefit, Daiana Stolz, MD, Clinic for Respiratory Medicine and Pulmonary Cell Research, University of Basel (Switzerland), called the data from this sham-controlled trial “really exciting and important.” However, she said, the larger AIRFLOW-3 trial is needed “to confirm this is an effective and safe treatment.”
 

Dr. Slebos receives consultancy fees from Aeris Therapeutics, Boston Scientific, Broncus Technologies, CSA Medical. Olympus, Portaero, PulmonX, PneumRx/BTG, and Nuvaira, which provided the funding for this study.

PARIS – High relative troponin I concentrations in the blood of patients with chronic obstructive pulmonary disease (COPD) has been found to be a remarkably powerful predictor of all-cause mortality even after researchers adjusted for all major cardiovascular and COPD prognostic indicators, according to a late-breaker presentation at the annual congress of the European Respiratory Society.

Troponin I is detectable in the plasma of most patients with COPD, but relative increases in troponin I correlate with greater relative increases in most cardiovascular and COPD risk factors, according to Benjamin Waschki, MD, Pulmonary Research Institute, LungenClinic, Grosshansdorf, Germany.

The relationship between increased troponin I and increased all-cause mortality was observed in an on-going prospective multicenter cohort of COPD patients followed at 31 centers in Germany. The cohort is called COSYCONET and it began in 2010. The current analysis evaluated 2,020 COPD patients without regard to stage of disease.

There were 136 deaths over the course of follow-up. Without adjustment, the hazard ratio (HR) for death was more than twofold higher in the highest quartile of troponin I (equal to or greater than 6.6 ng/mL), when compared with the lowest (under 2.5 ng/mL) (HR, 2.42; P less than .001). Graphically, the mortality curves for each of the quartiles began to separate at about 12 months, widening in a stepwise manner for greater likelihood of death from the lowest to highest quartiles.

The risk of death from any cause remained elevated for the highest relative to lowest troponin I quartiles after adjusting for cardiovascular risk factors and after adjusting for COPD severity. Again, there was a distinct stepwise separation of the mortality curves for each higher troponin quartile,

Of particular importance, troponin I remained predictive beyond the BODE index, which is a currently employed prognostic mortality predictor in COPD, according to Dr. Waschki. When defining elevated troponin as greater than 6 ng/ML and a high BODE score as greater than 4, mortality was higher for those with a high BODE and low troponin than a high troponin and low BODE, (P less than .001), but a high troponin I was associated with a higher risk of mortality when BODE was low (P less than .001). Moreover, when both troponin I and BODE were elevated, all-cause mortality was more than doubled, relative to those without either risk factor (HR, 2.56; P = .003), Dr. Waschki reported.

After researchers adjusted for major cardiovascular risk factors, such as history of MI and renal impairment, and for major COPD risk factors, such as 6-minute walk test and BODE index, those in the highest quartile had a more than 50% greater risk of death relative to those in the lower quartile over the 3 years of follow-up (HR, 1.69; P = .007), according to Dr. Waschki.

Although troponin I is best known for its diagnostic role in MI, it is now being evaluated as a risk stratifier for many chronic diseases, such as heart failure and chronic kidney disease, explained Dr. Waschki in providing background for this study. He reported that many groups are looking at this as a marker of risk in a variety of chronic diseases.

In fact, a group working independently published a study in COPD just weeks before the ERS Congress that was complementary to those presented by Dr. Waschki. In this study, the goal was to evaluate troponin I as a predictor of cardiovascular events and cardiovascular death (Adamson PD et al. J Am Coll Cardiol 2018;72:1126-37). Performed as a subgroup analysis of 1,599 COPD patients participating in a large treatment trial, there was an almost fourfold increase in the risk of cardiovascular events (HR, 3.7; P = .012) when those in the highest quintile of troponin I (greater than 7.7 ng/ML) were compared with those in the lowest quintile (less than 2.3 ng/mL).

When compared for cardiovascular death, the highest quintile, relative to the lowest quintile, had a more than 20-fold increased risk of cardiovascular death (HR 20.1; P = .005). In the Adamson et al. study, which evaluated inhaled therapies for COPD, treatment response had no impact on troponin I levels or on the risk of cardiovascular events or death.

Based on this study and his own data, Dr. Waschki believes troponin I, which is readily ordered laboratory value, appears to be a useful tool for identifying COPD patients at high risk of death.

“The major message is that after adjusting for all known COPD and cardiovascular risk factors, troponin I remains a significant independent predictor of mortality,” he said.

Dr. Waschki reports no relevant conflicts of interest.

PARIS – High relative troponin I concentrations in the blood of patients with chronic obstructive pulmonary disease (COPD) has been found to be a remarkably powerful predictor of all-cause mortality even after researchers adjusted for all major cardiovascular and COPD prognostic indicators, according to a late-breaker presentation at the annual congress of the European Respiratory Society.

Troponin I is detectable in the plasma of most patients with COPD, but relative increases in troponin I correlate with greater relative increases in most cardiovascular and COPD risk factors, according to Benjamin Waschki, MD, Pulmonary Research Institute, LungenClinic, Grosshansdorf, Germany.

The relationship between increased troponin I and increased all-cause mortality was observed in an on-going prospective multicenter cohort of COPD patients followed at 31 centers in Germany. The cohort is called COSYCONET and it began in 2010. The current analysis evaluated 2,020 COPD patients without regard to stage of disease.

There were 136 deaths over the course of follow-up. Without adjustment, the hazard ratio (HR) for death was more than twofold higher in the highest quartile of troponin I (equal to or greater than 6.6 ng/mL), when compared with the lowest (under 2.5 ng/mL) (HR, 2.42; P less than .001). Graphically, the mortality curves for each of the quartiles began to separate at about 12 months, widening in a stepwise manner for greater likelihood of death from the lowest to highest quartiles.

The risk of death from any cause remained elevated for the highest relative to lowest troponin I quartiles after adjusting for cardiovascular risk factors and after adjusting for COPD severity. Again, there was a distinct stepwise separation of the mortality curves for each higher troponin quartile,

Of particular importance, troponin I remained predictive beyond the BODE index, which is a currently employed prognostic mortality predictor in COPD, according to Dr. Waschki. When defining elevated troponin as greater than 6 ng/ML and a high BODE score as greater than 4, mortality was higher for those with a high BODE and low troponin than a high troponin and low BODE, (P less than .001), but a high troponin I was associated with a higher risk of mortality when BODE was low (P less than .001). Moreover, when both troponin I and BODE were elevated, all-cause mortality was more than doubled, relative to those without either risk factor (HR, 2.56; P = .003), Dr. Waschki reported.

After researchers adjusted for major cardiovascular risk factors, such as history of MI and renal impairment, and for major COPD risk factors, such as 6-minute walk test and BODE index, those in the highest quartile had a more than 50% greater risk of death relative to those in the lower quartile over the 3 years of follow-up (HR, 1.69; P = .007), according to Dr. Waschki.

Although troponin I is best known for its diagnostic role in MI, it is now being evaluated as a risk stratifier for many chronic diseases, such as heart failure and chronic kidney disease, explained Dr. Waschki in providing background for this study. He reported that many groups are looking at this as a marker of risk in a variety of chronic diseases.

In fact, a group working independently published a study in COPD just weeks before the ERS Congress that was complementary to those presented by Dr. Waschki. In this study, the goal was to evaluate troponin I as a predictor of cardiovascular events and cardiovascular death (Adamson PD et al. J Am Coll Cardiol 2018;72:1126-37). Performed as a subgroup analysis of 1,599 COPD patients participating in a large treatment trial, there was an almost fourfold increase in the risk of cardiovascular events (HR, 3.7; P = .012) when those in the highest quintile of troponin I (greater than 7.7 ng/ML) were compared with those in the lowest quintile (less than 2.3 ng/mL).

When compared for cardiovascular death, the highest quintile, relative to the lowest quintile, had a more than 20-fold increased risk of cardiovascular death (HR 20.1; P = .005). In the Adamson et al. study, which evaluated inhaled therapies for COPD, treatment response had no impact on troponin I levels or on the risk of cardiovascular events or death.

Based on this study and his own data, Dr. Waschki believes troponin I, which is readily ordered laboratory value, appears to be a useful tool for identifying COPD patients at high risk of death.

“The major message is that after adjusting for all known COPD and cardiovascular risk factors, troponin I remains a significant independent predictor of mortality,” he said.

Dr. Waschki reports no relevant conflicts of interest.

PARIS – High relative troponin I concentrations in the blood of patients with chronic obstructive pulmonary disease (COPD) has been found to be a remarkably powerful predictor of all-cause mortality even after researchers adjusted for all major cardiovascular and COPD prognostic indicators, according to a late-breaker presentation at the annual congress of the European Respiratory Society.

Troponin I is detectable in the plasma of most patients with COPD, but relative increases in troponin I correlate with greater relative increases in most cardiovascular and COPD risk factors, according to Benjamin Waschki, MD, Pulmonary Research Institute, LungenClinic, Grosshansdorf, Germany.

The relationship between increased troponin I and increased all-cause mortality was observed in an on-going prospective multicenter cohort of COPD patients followed at 31 centers in Germany. The cohort is called COSYCONET and it began in 2010. The current analysis evaluated 2,020 COPD patients without regard to stage of disease.

There were 136 deaths over the course of follow-up. Without adjustment, the hazard ratio (HR) for death was more than twofold higher in the highest quartile of troponin I (equal to or greater than 6.6 ng/mL), when compared with the lowest (under 2.5 ng/mL) (HR, 2.42; P less than .001). Graphically, the mortality curves for each of the quartiles began to separate at about 12 months, widening in a stepwise manner for greater likelihood of death from the lowest to highest quartiles.

The risk of death from any cause remained elevated for the highest relative to lowest troponin I quartiles after adjusting for cardiovascular risk factors and after adjusting for COPD severity. Again, there was a distinct stepwise separation of the mortality curves for each higher troponin quartile,

Of particular importance, troponin I remained predictive beyond the BODE index, which is a currently employed prognostic mortality predictor in COPD, according to Dr. Waschki. When defining elevated troponin as greater than 6 ng/ML and a high BODE score as greater than 4, mortality was higher for those with a high BODE and low troponin than a high troponin and low BODE, (P less than .001), but a high troponin I was associated with a higher risk of mortality when BODE was low (P less than .001). Moreover, when both troponin I and BODE were elevated, all-cause mortality was more than doubled, relative to those without either risk factor (HR, 2.56; P = .003), Dr. Waschki reported.

After researchers adjusted for major cardiovascular risk factors, such as history of MI and renal impairment, and for major COPD risk factors, such as 6-minute walk test and BODE index, those in the highest quartile had a more than 50% greater risk of death relative to those in the lower quartile over the 3 years of follow-up (HR, 1.69; P = .007), according to Dr. Waschki.

Although troponin I is best known for its diagnostic role in MI, it is now being evaluated as a risk stratifier for many chronic diseases, such as heart failure and chronic kidney disease, explained Dr. Waschki in providing background for this study. He reported that many groups are looking at this as a marker of risk in a variety of chronic diseases.

In fact, a group working independently published a study in COPD just weeks before the ERS Congress that was complementary to those presented by Dr. Waschki. In this study, the goal was to evaluate troponin I as a predictor of cardiovascular events and cardiovascular death (Adamson PD et al. J Am Coll Cardiol 2018;72:1126-37). Performed as a subgroup analysis of 1,599 COPD patients participating in a large treatment trial, there was an almost fourfold increase in the risk of cardiovascular events (HR, 3.7; P = .012) when those in the highest quintile of troponin I (greater than 7.7 ng/ML) were compared with those in the lowest quintile (less than 2.3 ng/mL).

When compared for cardiovascular death, the highest quintile, relative to the lowest quintile, had a more than 20-fold increased risk of cardiovascular death (HR 20.1; P = .005). In the Adamson et al. study, which evaluated inhaled therapies for COPD, treatment response had no impact on troponin I levels or on the risk of cardiovascular events or death.

Based on this study and his own data, Dr. Waschki believes troponin I, which is readily ordered laboratory value, appears to be a useful tool for identifying COPD patients at high risk of death.

“The major message is that after adjusting for all known COPD and cardiovascular risk factors, troponin I remains a significant independent predictor of mortality,” he said.

Dr. Waschki reports no relevant conflicts of interest.

PARIS – In patients with a chronic obstructive pulmonary disease (COPD) exacerbation, initiating azithromycin at the time of hospitalization provided improvement in a variety of outcomes at 90 days, including risk of death, according to a placebo-controlled trial presented as a late-breaker at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

In patients with COPD, “azithromycin initiated in the acute setting and continued for 3 months appears to be safe and potentially effective,” reported Wim Janssens, MD, PhD, division of respiratory medicine, University Hospital, Leuven, Belgium.

The phrase “potentially effective” was used because the primary endpoint, which was time to treatment failure, fell just short of statistical significance (P = .053), but the rate of treatment failures, which was a coprimary endpoint (P = .04), and all of the secondary endpoints, including mortality at 90 days (P = .027), need for treatment intensification (P = .02) and need for an intensive care unit (ICU) admission (P = .003), were significantly lower in the group receiving azithromycin rather than placebo.

In a previous trial, chronic azithromycin therapy on top of usual care in patients frequently hospitalized for COPD was associated with a reduction in the risk of exacerbations and an improvement in quality of life (N Engl J Med. 2011;365:689-98). However, Dr. Janssens explained that this strategy is not commonly used because it was associated with a variety of adverse events, not least of which was QTc prolongation.

The study at the meeting, called the BACE trial, was designed to test whether azithromycin could be employed in a more targeted approach to control exacerbations. In the study, 301 COPD patients hospitalized with an acute exacerbation were randomized within 48 hours of admission to azithromycin or placebo. For the first 3 days, azithromycin was administered in a 500-mg dose. Thereafter, the dose was 250 mg every second day. Treatment was stopped at 90 days.

The primary outcome was time to treatment failure, a novel composite endpoint of any of three events: the need for treatment intensification, the need for step-up hospital care (either ICU admission or hospital readmission), or death by any cause. The two treatment arms were also compared for safety, including QTc prolongation.

The treatment failure rates were 49% in the azithromycin arm and 60% in the placebo arm, producing a hazard ratio (HR) of 0.73. Although this outcome fell short of significance, Dr. Janssens suggested that benefits over the 90 days of treatment are supported by the secondary outcomes. However, he also cautioned that most relative advantages for azithromycin over placebo were found to dissipate over time.

“The maximum separation between the azithromycin and placebo arms [for the primary outcome] occurred at 120 days or 30 days after the medication was stopped,” Dr. Janssens reported. After this point, the two arms converged and eventually overlapped.

However, the acute benefits appeared to be substantial. For example, average hospital stay over the 90-day treatment period was reduced from 40 to 10 days (P = .0061), and the ICU days fell from 11 days to 3 days in the azithromycin relative to the placebo group. According to Dr. Janssens, the difference in hospital stay carries “important health economic potential that deserves further attention.”

Of the three QTc events that occurred during the course of the study, one was observed in the placebo group. There was no significant difference in this or other adverse events, according to Dr. Janssens.

It is notable that the design for the BACE trial called for 500 patients. When enrollment was slow, the design was changed on the basis of power calculations indicating that 300 patients would be sufficient to demonstrate a difference. It is unclear whether a larger study would have permitted the difference in the primary endpoint to advance from a trend.

Dr. Janssens reports no conflicts of interest relevant to this study.

PARIS – In patients with a chronic obstructive pulmonary disease (COPD) exacerbation, initiating azithromycin at the time of hospitalization provided improvement in a variety of outcomes at 90 days, including risk of death, according to a placebo-controlled trial presented as a late-breaker at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

In patients with COPD, “azithromycin initiated in the acute setting and continued for 3 months appears to be safe and potentially effective,” reported Wim Janssens, MD, PhD, division of respiratory medicine, University Hospital, Leuven, Belgium.

The phrase “potentially effective” was used because the primary endpoint, which was time to treatment failure, fell just short of statistical significance (P = .053), but the rate of treatment failures, which was a coprimary endpoint (P = .04), and all of the secondary endpoints, including mortality at 90 days (P = .027), need for treatment intensification (P = .02) and need for an intensive care unit (ICU) admission (P = .003), were significantly lower in the group receiving azithromycin rather than placebo.

In a previous trial, chronic azithromycin therapy on top of usual care in patients frequently hospitalized for COPD was associated with a reduction in the risk of exacerbations and an improvement in quality of life (N Engl J Med. 2011;365:689-98). However, Dr. Janssens explained that this strategy is not commonly used because it was associated with a variety of adverse events, not least of which was QTc prolongation.

The study at the meeting, called the BACE trial, was designed to test whether azithromycin could be employed in a more targeted approach to control exacerbations. In the study, 301 COPD patients hospitalized with an acute exacerbation were randomized within 48 hours of admission to azithromycin or placebo. For the first 3 days, azithromycin was administered in a 500-mg dose. Thereafter, the dose was 250 mg every second day. Treatment was stopped at 90 days.

The primary outcome was time to treatment failure, a novel composite endpoint of any of three events: the need for treatment intensification, the need for step-up hospital care (either ICU admission or hospital readmission), or death by any cause. The two treatment arms were also compared for safety, including QTc prolongation.

The treatment failure rates were 49% in the azithromycin arm and 60% in the placebo arm, producing a hazard ratio (HR) of 0.73. Although this outcome fell short of significance, Dr. Janssens suggested that benefits over the 90 days of treatment are supported by the secondary outcomes. However, he also cautioned that most relative advantages for azithromycin over placebo were found to dissipate over time.

“The maximum separation between the azithromycin and placebo arms [for the primary outcome] occurred at 120 days or 30 days after the medication was stopped,” Dr. Janssens reported. After this point, the two arms converged and eventually overlapped.

However, the acute benefits appeared to be substantial. For example, average hospital stay over the 90-day treatment period was reduced from 40 to 10 days (P = .0061), and the ICU days fell from 11 days to 3 days in the azithromycin relative to the placebo group. According to Dr. Janssens, the difference in hospital stay carries “important health economic potential that deserves further attention.”

Of the three QTc events that occurred during the course of the study, one was observed in the placebo group. There was no significant difference in this or other adverse events, according to Dr. Janssens.

It is notable that the design for the BACE trial called for 500 patients. When enrollment was slow, the design was changed on the basis of power calculations indicating that 300 patients would be sufficient to demonstrate a difference. It is unclear whether a larger study would have permitted the difference in the primary endpoint to advance from a trend.

Dr. Janssens reports no conflicts of interest relevant to this study.

PARIS – In patients with a chronic obstructive pulmonary disease (COPD) exacerbation, initiating azithromycin at the time of hospitalization provided improvement in a variety of outcomes at 90 days, including risk of death, according to a placebo-controlled trial presented as a late-breaker at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

In patients with COPD, “azithromycin initiated in the acute setting and continued for 3 months appears to be safe and potentially effective,” reported Wim Janssens, MD, PhD, division of respiratory medicine, University Hospital, Leuven, Belgium.

The phrase “potentially effective” was used because the primary endpoint, which was time to treatment failure, fell just short of statistical significance (P = .053), but the rate of treatment failures, which was a coprimary endpoint (P = .04), and all of the secondary endpoints, including mortality at 90 days (P = .027), need for treatment intensification (P = .02) and need for an intensive care unit (ICU) admission (P = .003), were significantly lower in the group receiving azithromycin rather than placebo.

In a previous trial, chronic azithromycin therapy on top of usual care in patients frequently hospitalized for COPD was associated with a reduction in the risk of exacerbations and an improvement in quality of life (N Engl J Med. 2011;365:689-98). However, Dr. Janssens explained that this strategy is not commonly used because it was associated with a variety of adverse events, not least of which was QTc prolongation.

The study at the meeting, called the BACE trial, was designed to test whether azithromycin could be employed in a more targeted approach to control exacerbations. In the study, 301 COPD patients hospitalized with an acute exacerbation were randomized within 48 hours of admission to azithromycin or placebo. For the first 3 days, azithromycin was administered in a 500-mg dose. Thereafter, the dose was 250 mg every second day. Treatment was stopped at 90 days.

The primary outcome was time to treatment failure, a novel composite endpoint of any of three events: the need for treatment intensification, the need for step-up hospital care (either ICU admission or hospital readmission), or death by any cause. The two treatment arms were also compared for safety, including QTc prolongation.

The treatment failure rates were 49% in the azithromycin arm and 60% in the placebo arm, producing a hazard ratio (HR) of 0.73. Although this outcome fell short of significance, Dr. Janssens suggested that benefits over the 90 days of treatment are supported by the secondary outcomes. However, he also cautioned that most relative advantages for azithromycin over placebo were found to dissipate over time.

“The maximum separation between the azithromycin and placebo arms [for the primary outcome] occurred at 120 days or 30 days after the medication was stopped,” Dr. Janssens reported. After this point, the two arms converged and eventually overlapped.

However, the acute benefits appeared to be substantial. For example, average hospital stay over the 90-day treatment period was reduced from 40 to 10 days (P = .0061), and the ICU days fell from 11 days to 3 days in the azithromycin relative to the placebo group. According to Dr. Janssens, the difference in hospital stay carries “important health economic potential that deserves further attention.”

Of the three QTc events that occurred during the course of the study, one was observed in the placebo group. There was no significant difference in this or other adverse events, according to Dr. Janssens.

It is notable that the design for the BACE trial called for 500 patients. When enrollment was slow, the design was changed on the basis of power calculations indicating that 300 patients would be sufficient to demonstrate a difference. It is unclear whether a larger study would have permitted the difference in the primary endpoint to advance from a trend.

Dr. Janssens reports no conflicts of interest relevant to this study.

Prolonged exposure to secondhand smoke during childhood is associated with a greater risk of death from chronic obstructive pulmonary disease in adulthood, new research has found.

pmphoto/iStockphoto.com

SOURCE: Diver WR et al. Am J Prev Med 2018;55[3]:345-52. doi: 10.1016/j.amepre.2018.05.005.

Prolonged exposure to secondhand smoke during childhood is associated with a greater risk of death from chronic obstructive pulmonary disease in adulthood, new research has found.

pmphoto/iStockphoto.com

SOURCE: Diver WR et al. Am J Prev Med 2018;55[3]:345-52. doi: 10.1016/j.amepre.2018.05.005.

Prolonged exposure to secondhand smoke during childhood is associated with a greater risk of death from chronic obstructive pulmonary disease in adulthood, new research has found.

pmphoto/iStockphoto.com

SOURCE: Diver WR et al. Am J Prev Med 2018;55[3]:345-52. doi: 10.1016/j.amepre.2018.05.005.

Rapid declines in spirometric measures of lung function were associated with higher risks of cardiovascular disease, according to a recent analysis of a large, prospective cohort study.

Rapid declines in forced expiratory volume in 1 second (FEV₁) were associated with increased incidence of heart failure, stroke, and death in the analysis of the ARIC (Atherosclerosis Risk in Communities) study.

The risk of incident heart failure among FEV₁ rapid decliners was particularly high, with a fourfold increase within 12 months. That suggests clinicians should carefully consider incipient heart failure in patients with rapid changes in FEV₁, investigators reported in the Journal of the American College of Cardiology.

Rapid declines in forced vital capacity (FVC) were also associated with higher incidences of heart failure and death in the analysis by Odilson M. Silvestre, MD, of the division of cardiovascular medicine at Brigham and Women’s Hospital, Boston, and colleagues.

The analysis included a total of 10,351 ARIC participants with a mean follow-up of 17 years. All had undergone spirometry at the first study visit between 1987 and 1989, and on the second visit between 1990 and 1992.

One-quarter of participants were classified as FEV₁ rapid decliners, defined by an FEV₁ decrease of at least 1.9% per year. Likewise, one-quarter of participants were classified as FVC rapid decliners, based on an FVC decrease of at least 2.1%.

Rapid decline in FEV₁ was associated with a higher risk of incident heart failure (hazard ratio, 1.17; 95% confidence interval, 1.04-1.33; P = .010), and was most prognostic in the first year of follow-up (HR, 4.22; 95% CI, 1.34-13.26; P = .01), investigators said.

Rapid decline in FVC was likewise associated with a greater heart failure risk (HR, 1.27; 95% CI, 1.12-1.44; P less than .001).

Increased heart failure risk persisted after excluding patients with incident coronary heart disease in both the FEV₁ and FVC rapid decliners, the investigators said.

A rapid decline in FEV₁ was also associated with a higher stroke risk (HR, 1.25; 95% CI, 1.04-1.50; P = .015).

FEV₁ rapid decliners had a higher overall rate of incident cardiovascular disease than those without rapid decline, even after adjustment for baseline variables such as age, sex, race, body mass index, and heart rate (HR, 1.15; 95% CI, 1.04-1.26; P = .004), and FVC rapid decliners likewise had a 19% greater risk of the composite endpoint (HR, 1.19; 95% CI, 1.08-1.32; P less than .001).

The National Heart, Lung, and Blood Institute, the American Heart Association, and other sources supported the study. Dr. Silvestre reported having no relevant conflicts.

SOURCE: Silvestre OM et al. J Am Coll Cardiol. 2018 Sep 4;72(10):1109-22.

Rapid declines in spirometric measures of lung function were associated with higher risks of cardiovascular disease, according to a recent analysis of a large, prospective cohort study.

Rapid declines in forced expiratory volume in 1 second (FEV₁) were associated with increased incidence of heart failure, stroke, and death in the analysis of the ARIC (Atherosclerosis Risk in Communities) study.

The risk of incident heart failure among FEV₁ rapid decliners was particularly high, with a fourfold increase within 12 months. That suggests clinicians should carefully consider incipient heart failure in patients with rapid changes in FEV₁, investigators reported in the Journal of the American College of Cardiology.

Rapid declines in forced vital capacity (FVC) were also associated with higher incidences of heart failure and death in the analysis by Odilson M. Silvestre, MD, of the division of cardiovascular medicine at Brigham and Women’s Hospital, Boston, and colleagues.

The analysis included a total of 10,351 ARIC participants with a mean follow-up of 17 years. All had undergone spirometry at the first study visit between 1987 and 1989, and on the second visit between 1990 and 1992.

One-quarter of participants were classified as FEV₁ rapid decliners, defined by an FEV₁ decrease of at least 1.9% per year. Likewise, one-quarter of participants were classified as FVC rapid decliners, based on an FVC decrease of at least 2.1%.

Rapid decline in FEV₁ was associated with a higher risk of incident heart failure (hazard ratio, 1.17; 95% confidence interval, 1.04-1.33; P = .010), and was most prognostic in the first year of follow-up (HR, 4.22; 95% CI, 1.34-13.26; P = .01), investigators said.

Rapid decline in FVC was likewise associated with a greater heart failure risk (HR, 1.27; 95% CI, 1.12-1.44; P less than .001).

Increased heart failure risk persisted after excluding patients with incident coronary heart disease in both the FEV₁ and FVC rapid decliners, the investigators said.

A rapid decline in FEV₁ was also associated with a higher stroke risk (HR, 1.25; 95% CI, 1.04-1.50; P = .015).

FEV₁ rapid decliners had a higher overall rate of incident cardiovascular disease than those without rapid decline, even after adjustment for baseline variables such as age, sex, race, body mass index, and heart rate (HR, 1.15; 95% CI, 1.04-1.26; P = .004), and FVC rapid decliners likewise had a 19% greater risk of the composite endpoint (HR, 1.19; 95% CI, 1.08-1.32; P less than .001).

The National Heart, Lung, and Blood Institute, the American Heart Association, and other sources supported the study. Dr. Silvestre reported having no relevant conflicts.

SOURCE: Silvestre OM et al. J Am Coll Cardiol. 2018 Sep 4;72(10):1109-22.

Rapid declines in spirometric measures of lung function were associated with higher risks of cardiovascular disease, according to a recent analysis of a large, prospective cohort study.

Rapid declines in forced expiratory volume in 1 second (FEV₁) were associated with increased incidence of heart failure, stroke, and death in the analysis of the ARIC (Atherosclerosis Risk in Communities) study.

The risk of incident heart failure among FEV₁ rapid decliners was particularly high, with a fourfold increase within 12 months. That suggests clinicians should carefully consider incipient heart failure in patients with rapid changes in FEV₁, investigators reported in the Journal of the American College of Cardiology.

Rapid declines in forced vital capacity (FVC) were also associated with higher incidences of heart failure and death in the analysis by Odilson M. Silvestre, MD, of the division of cardiovascular medicine at Brigham and Women’s Hospital, Boston, and colleagues.

The analysis included a total of 10,351 ARIC participants with a mean follow-up of 17 years. All had undergone spirometry at the first study visit between 1987 and 1989, and on the second visit between 1990 and 1992.

One-quarter of participants were classified as FEV₁ rapid decliners, defined by an FEV₁ decrease of at least 1.9% per year. Likewise, one-quarter of participants were classified as FVC rapid decliners, based on an FVC decrease of at least 2.1%.

Rapid decline in FEV₁ was associated with a higher risk of incident heart failure (hazard ratio, 1.17; 95% confidence interval, 1.04-1.33; P = .010), and was most prognostic in the first year of follow-up (HR, 4.22; 95% CI, 1.34-13.26; P = .01), investigators said.

Rapid decline in FVC was likewise associated with a greater heart failure risk (HR, 1.27; 95% CI, 1.12-1.44; P less than .001).

Increased heart failure risk persisted after excluding patients with incident coronary heart disease in both the FEV₁ and FVC rapid decliners, the investigators said.

A rapid decline in FEV₁ was also associated with a higher stroke risk (HR, 1.25; 95% CI, 1.04-1.50; P = .015).

FEV₁ rapid decliners had a higher overall rate of incident cardiovascular disease than those without rapid decline, even after adjustment for baseline variables such as age, sex, race, body mass index, and heart rate (HR, 1.15; 95% CI, 1.04-1.26; P = .004), and FVC rapid decliners likewise had a 19% greater risk of the composite endpoint (HR, 1.19; 95% CI, 1.08-1.32; P less than .001).

The National Heart, Lung, and Blood Institute, the American Heart Association, and other sources supported the study. Dr. Silvestre reported having no relevant conflicts.

SOURCE: Silvestre OM et al. J Am Coll Cardiol. 2018 Sep 4;72(10):1109-22.