No abstract

a b s t r a c tObjectives: The role of Pseudomonas aeruginosa in the long-term prognosis of chronic obstructive pulmonary disease (COPD) is unknown. The purpose of this study was to determine whether P. aeruginosa is associated with increased risk of exacerbations or death in patients with COPD. Methods: This is a multiregional epidemiological study based on complete data on COPD outpatients between 1 January 2010 and 31 October 2017 and corresponding microbiology and national register data. Time-dependent Cox proportional hazards models and propensity matching was used to estimate hospitalization-demanding exacerbations and death after 2 years, separately and in combination. Results: A total of 22 053 COPD outpatients were followed for a median of 1082 days (interquartilerange: 427e1862). P. aeruginosa was present in 905 (4.1%) patients. During 730 days of follow-up, P. aeruginosa strongly and independently predicted an increased risk of hospitalization for exacerbation or all-cause death (HR 2.8, 95%CI 2.2e3.6; p <0.0001) and all-cause death (HR 2.7, 95%CI 2.3e3.4; p <0.0001) in analyses adjusted for known and suspected confounders. The signal remained unchanged in unadjusted analyses as well as propensity-matched subgroup analyses. Among patients 'ever colonized' with P. aeruginosa, the incidence of hospital-demanding exacerbations doubled after the time of the first colonization. Conclusions: COPD patients in whom P. aeruginosa can be cultured from the airways had a markedly increased risk of exacerbations and death. It is still not clear whether this risk can be reduced by offering patients targeted antipseudomonal antibiotics. A randomized trial is currently recruiting patients to clarify this (ClinicalTrials.gov: NCT03262142).

IntroductionA large group of patients with chronic obstructive pulmonary disease (COPD) are exposed to an overload of oral corticosteroids (OCS) due to repeated exacerbations. This is associated with potential serious adverse effects. Therefore, we evaluated the impact of a recommended reduction of OCS duration in 2014 on the risk of pneumonia hospitalisation and all-cause mortality in patients with acute exacerbation of COPD (AECOPD).MethodsThis was a nationwide observational cohort study that was based on linked administrative registry data between 1 January 2010 and 31 October 2017. 10 152 outpatients with COPD (median age 70 years) treated with either a short (≤250 mg) or long course (>250 mg) of OCS for AECOPD were included in the study. Cox proportional hazards regression models were used to derive an estimation of multivariable adjusted HRs (aHRs) for pneumonia hospitalisation or all-cause mortality combined and pneumonia hospitalisation and all-cause mortality, separately.ResultsThe long course of OCS treatment for AECOPD was associated with an increased 1-year risk of pneumonia hospitalisation or all-cause mortality (aHR 1.3, 95% CI 1.1 to 1.4; p<0.0001), pneumonia hospitalisation (aHR 1.2, 95% CI 1.0 to 1.3; p=0.0110) and all-cause mortality (aHR 1.8, 95% CI 1.5 to 2.2; p<0.0001) as compared with the short course of OCS treatment. These results were confirmed in several sensitivity analyses.ConclusionThe change of recommendations from long courses to short courses of OCS for AECOPD in 2014 was strongly associated with a decrease in pneumonia admissions and all-cause mortality, in favour of short courses of OCS.

Social distancing measures introduced on March 12, 2020 in Denmark during the COVID-19 pandemic may affect non-COVID-19 admissions for severe acute exacerbation of chronic obstructive pulmonary disease (s-AECOPD). We compared rates of s-AECOPD in a nationwide, observational, semi-experimental cohort study comparing data from all Danish inhabitants between calendar week 1 through 25 in 2019 and 2020. In a sub-cohort of COPD patients, we examined incidence of s-AECOPD, admissions to intensive care unit and all-cause mortality. A total of 3.0 million inhabitants aged 40+ years, corresponding to 3.0 million person-years, were followed for s-AECOPD. In the social distancing period in 2020, there were 6,212 incidents of s-AECOPD compared to 11,260 incidents of s-AECOPD in 2019, resulting in a 45% relative risk reduction. In the COPD cohort (N=16,675), we observed a lower risk of s-AECOPD with the social distancing period (subdistribution hazard ratio [sHR] 0.34, 95%-confidence interval [CI]: 0.33, 0.36, absolute risk: 25.4% in 2020 and 42.8% in 2019). The risk of admissions to intensive care unit was reduced (sHR 0.64, CI: 0.47, 0.87) as was all-cause mortality (normal HR 0.83, CI: 0.76, 0.90). Overall, the social distancing period was associated with a significant risk reduction for hospital admittance with s-AECOPD.