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. 2022 Aug 23;23(1):213.
doi: 10.1186/s12931-022-02123-5.

Prognostic risk factors for moderate-to-severe exacerbations in patients with chronic obstructive pulmonary disease: a systematic literature review

John R Hurst  1 , MeiLan K Han  2 , Barinder Singh  3 , Sakshi Sharma  4 , Gagandeep Kaur  3 , Enrico de Nigris  5 , Ulf Holmgren  6 , Mohd Kashif Siddiqui  3
Affiliations

Prognostic risk factors for moderate-to-severe exacerbations in patients with chronic obstructive pulmonary disease: a systematic literature review

John R Hurst et al. Respir Res. .

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. COPD exacerbations are associated with a worsening of lung function, increased disease burden, and mortality, and, therefore, preventing their occurrence is an important goal of COPD management. This review was conducted to identify the evidence base regarding risk factors and predictors of moderate-to-severe exacerbations in patients with COPD.

Methods: A literature review was performed in Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register of Controlled Trials (CENTRAL). Searches were conducted from January 2015 to July 2019. Eligible publications were peer-reviewed journal articles, published in English, that reported risk factors or predictors for the occurrence of moderate-to-severe exacerbations in adults age ≥ 40 years with a diagnosis of COPD.

Results: The literature review identified 5112 references, of which 113 publications (reporting results for 76 studies) met the eligibility criteria and were included in the review. Among the 76 studies included, 61 were observational and 15 were randomized controlled clinical trials. Exacerbation history was the strongest predictor of future exacerbations, with 34 studies reporting a significant association between history of exacerbations and risk of future moderate or severe exacerbations. Other significant risk factors identified in multiple studies included disease severity or bronchodilator reversibility (39 studies), comorbidities (34 studies), higher symptom burden (17 studies), and higher blood eosinophil count (16 studies).

Conclusions: This systematic literature review identified several demographic and clinical characteristics that predict the future risk of COPD exacerbations. Prior exacerbation history was confirmed as the most important predictor of future exacerbations. These prognostic factors may help clinicians identify patients at high risk of exacerbations, which are a major driver of the global burden of COPD, including morbidity and mortality.

Keywords: Biomarkers; COPD; Comorbidities; Exacerbations; Hospitalization; Predictors; Systematic literature review.

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Conflict of interest statement

JRH reports consulting fees from AstraZeneca; speaker fees from AstraZeneca, Chiesi, Pfizer, and Takeda; and travel support from GlaxoSmithKline and AstraZeneca. MKH reports assistance with conduction of this research and publication from AstraZeneca; personal fees from Aerogen, Altesa Biopharma, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, DevPro, GlaxoSmithKline, Integrity, Medscape, Merck, Mylan, NACE, Novartis, Polarean, Pulmonx, Regeneron, Sanofi, Teva, Verona, United Therapeutics, and UpToDate; either in kind research support or funds paid to the institution from the American Lung Association, AstraZeneca, Biodesix, Boehringer Ingelheim, the COPD Foundation, Gala Therapeutics, the NIH, Novartis, Nuvaira, Sanofi, and Sunovion; participation in Data Safety Monitoring Boards for Novartis and Medtronic with funds paid to the institution; and stock options from Altesa Biopharma and Meissa Vaccines. BS, GK, and MKS are former employees of Parexel International. SS is an employee of Parexel International, which was funded by AstraZeneca to conduct this analysis. EdN is a former employee of AstraZeneca and previously held stock and/or stock options in the company. UH is an employee of AstraZeneca and holds stock and/or stock options in the company.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram of studies through the systematic review process. CA conference abstract, CENTRAL Cochrane Central Register of Controlled Trials, PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Fig. 2
Fig. 2
Risk factors for moderate-to-severe exacerbations in patients with COPD. Factors with > 30 supporting studies shown as large circles; factors with ≤ 30 supporting studies shown as small circles and should be interpreted cautiously. BDR bronchodilator reversibility, BMI body mass index, COPD chronic obstructive pulmonary disease, EOS eosinophil, QoL quality of life
Fig. 3
Fig. 3
Summary of risk factors for exacerbation events. aTreatment impact studies removed. BDR bronchodilator reversibility, BMI body mass index, COPD chronic obstructive pulmonary disease, EOS eosinophil, QoL quality of life
Fig. 4
Fig. 4
Exacerbation history as a risk factor for moderate-to-severe exacerbations. Yun 2018 included two studies; the study from which data were extracted (COPDGene or ECLIPSE) is listed in parentheses. CI confidence interval, ES effect size
Fig. 5
Fig. 5
Exacerbation history as a risk factor for severe exacerbations. Where data have been extracted from a linked publication rather than the primary publication, the linked publication is listed in parentheses. CI confidence interval, ES, effect size
Fig. 6
Fig. 6
Comorbidities as risk factors for moderate-to-severe exacerbations. Yun 2018 included two studies; the study from which data were extracted (COPDGene or ECLIPSE) is listed in parentheses. Where data have been extracted from a linked publication rather than the primary publication, the linked publication is listed in parentheses. CI confidence interval, ES effect size, GERD gastroesophageal disease
Fig. 7
Fig. 7
Comorbidities as risk factors for severe exacerbations. Where data have been extracted from a linked publication rather than the primary publication, the linked publication is listed in parentheses. CI confidence interval, CKD, chronic kidney disease, ES effect size
Fig. 8
Fig. 8
Disease severity as a risk factor for moderate-to-severe exacerbations. Yun 2018 included two studies; the study from which data were extracted (COPDGene or ECLIPSE) is listed in parentheses. Where data have been extracted from a linked publication rather than the primary publication, the linked publication is listed in parentheses. CI confidence interval, ES effect size, FEV1 forced expiratory volume in 1 s, FVC, forced vital capacity, GOLD Global Initiative for Obstructive Lung Disease, HR hazard ratio, OR odds ratio
Fig. 9
Fig. 9
Disease severity and BDR as risk factors for severe exacerbations. ACCP American College of Chest Physicians, ACOS Asthma-COPD overlap syndrome, ATS American Thoracic Society, BDR bronchodilator reversibility, CI confidence interval, ERS European Respiratory Society, ES effect size, FEV1 forced expiratory volume in 1 s, FVC forced vital capacity, GINA Global Initiative for Asthma, GOLD Global Initiative for Obstructive Lung Disease
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