IntroductionDepressive symptoms appear more often among patients with chronic obstructive pulmonary disease (COPD) and are associated with reduced disease control and increased mortality. Both smoking and COPD increase the risk of depressive symptoms. Whether smoking cessation among COPD patients affects the occurrence of depressive symptoms is unknown. We hypothesised that smoking cessation in patients with COPD leads to reduced use of antidepressants and fewer admissions to psychiatric hospitals with depression, anxiety or bipolar disorder.MethodsWe conducted a nationwide retrospective case-control study, in patients from The Danish Register for Chronic Obstructive Pulmonary Disease (DrCOPD) with spirometry verified COPD, age ≥40 years, a history of smoking and absence of cancer. Consistent smokers were matched 1:1 with ex-smokers using a propensity score model. Prescription fillings of antidepressants and risk of admissions to psychiatric hospitals with either depression, anxiety or bipolar disorder both descriptively was assessed by Cox proportional hazard models.ResultsWe included 21 184 patients. A total of n=2011 consistent smokers collected antidepressant prescriptions compared with 1821 ex-smokers. Consistent smoking was associated with increased risk of filling prescription on antidepressants (HR 1.4, 95% CI 1.3–1.5, p<0.0001). and with increased risk of psychiatric hospital admission with either depression, anxiety or bipolar disorder (HR 2.0, 95% CI 1.6–2.5). The associations persisted after adjustment for former use of antidepressants.ConclusionConsistent smoking among COPD patients was associated with increased use of antidepressants and admissions to psychiatric hospitals with either depression, anxiety or bipolar disorder, compared to smoking cessation.

Roflumilast is given as an add-on to inhalation medication in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis. Animal experiments have documented deleterious effects of roflumilast in bacterial infections, but trials have not reported the risk of bacterial infections in patients. The objective of this study is to determine, among outpatients with severe COPD in a two-year follow-up period, the risk of hospitalization-requiring pneumonia, severe acute exacerbation in COPD (AECOPD-hosp), and death. Patients with COPD using roflumilast (roflumilast users) were compared to a propensity score-matched COPD control group not using roflumilast (non-roflumilast users). Roflumilast users had an increased 2-year risk of hospitalization-requiring pneumonia (HR 1.5, 95% CI 1.3 to 1.8, p-value < 0.0001) compared to controls, and of AECOPD-Hosp (hazard ratio(HR) 1.6, 95%, confidence interval (CI) 1.5 to 1.8, p-value < 0.0001) and. When adding an active comparator (theophylline) as a matching variable, the signal was largely unchanged. In conclusion, roflumilast was associated with an increased number of hospitalizations for pneumonia and for AECOPD. Since trials have not reported risks of bacterial complications and data regarding severe exacerbations in roflumilast users are sparse and diverging, these data are concerning. Trials focused on the risk of pneumonia, AECOPD, and other bacterial infections in roflumilast users are needed urgently.

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