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Randomized Controlled Trial
. 2020 Jan 6;21(1):5.
doi: 10.1186/s12931-019-1262-0.

Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis

Benjamin F Hartley  1 , Neil C Barnes  2   3 , Sally Lettis  4 , Chris H Compton  2 , Alberto Papi  5 , Paul Jones  2   6
Affiliations
Randomized Controlled Trial

Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis

Benjamin F Hartley et al. Respir Res. .

Abstract

Background: Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear.

Methods: This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox's proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation.

Results: Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year.

Conclusions: The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations.

Keywords: Chronic obstructive pulmonary disease; Exacerbation; Meta-analysis; Pneumonia.

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Conflict of interest statement

The authors declare the following real or perceived conflicts of interest during the last 3 years in relation to this work. NCB, CHC, SL, PJ are employees of and hold stock in GlaxoSmithKline. BFH is contracted to work on behalf of GlaxoSmithKline plc through a clinical research organization and holds stock in GlaxoSmithKline. AP reports grants, personal fees, and/or reimbursement of travel expenses from AstraZeneca, Chiesi, Boehringer Ingelheim, GlaxoSmithKline, Menarini, Merck Sharp & Dohme, Mundipharma, Novartis, Teva, Sanofi, and Zambon.

Figures

Fig. 1
Fig. 1
Hazard ratios (95% confidence intervals [CIs]) for pneumonia from selected seven-covariate pneumonia model. BMI body mass index, GOLD Global Initiative for Chronic Obstructive Lung Disease, ICS inhaled corticosteroids
Fig. 2
Fig. 2
Survival curves (95% CI bands) from selected pneumonia model subgroups showing probability of first pneumonia during year on study treatment. Cell header line 1: Age (years), sex, Global Initiative for Chronic Obstructive Lung Disease stage; Cell header line 2: Body mass index, number of exacerbations in the prior year. Numbers of patients presented are subgroup numbers; patients without covariates did not contribute to the model. All cells are shown in S1. CI confidence interval, ICS inhaled corticosteroids
Fig. 3
Fig. 3
Probabilities (95% CIs) of pneumonia during first year by BMI decile (direct adjusted probabilities). BMI body mass index, CI confidence interval, ICS inhaled corticosteroids
Fig. 4
Fig. 4
Hazard ratios (95% CIs) for exacerbation from selected seven-covariate exacerbation model. BMI body mass index, GOLD Global Initiative for Chronic Obstructive Lung Disease, ICS inhaled corticosteroids
Fig. 5
Fig. 5
Survival curves (95% CI bands) from selected exacerbation model subgroups showing probability of first exacerbation during year on study treatment. Cell header line 1: age (years), sex, Global Initiative for Chronic Obstructive Lung Disease stage; Cell header line 2: Body mass index, number of exacerbations in the prior year. Numbers of patients presented are subgroup numbers; patients without covariates did not contribute to the model. CI confidence interval, ICS inhaled corticosteroids
Fig. 6
Fig. 6
Hazard ratios (95% CIs) for exacerbation from selected Cox pneumonia model. BMI body mass index, GOLD Global Initiative for Chronic Obstructive Lung Disease, ICS inhaled corticosteroids
Fig. 7
Fig. 7
Survival curves (95% CI bands) from selected pneumonia model subgroups showing probability of first exacerbation during year on study treatment. Cell header line 1: age (years), sex, Global Initiative for Chronic Obstructive Lung Disease stage; Cell header line 2: Body mass index, number of exacerbations in the prior year. Numbers of patients presented are subgroup numbers; patients without covariates did not contribute to the model. All cells are shown in S2. CI confidence interval, ICS inhaled corticosteroids
See this image and copyright information in PMC

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