Clinically Important Deterioration (CID) and Ageing in COPD: A Systematic Review and Meta-Regression Analysis According to PRISMA Statement

Abstract

Purpose

Clinically important deterioration (CID) is a composite endpoint developed to quantify the impact of pharmacological treatment in clinical trials for Chronic Obstructive Pulmonary Disease (COPD), also showing a prognostic value. CID is defined as any of the following condition: forced expiratory volume in 1 s decrease ≥100 mL from baseline, and/or St. George’s Respiratory Questionnaire total score increase ≥4-unit from baseline, and/or the occurrence of a moderate-to-severe exacerbation of COPD. Although most COPD patients experience a clinical worsening as they get older, to date, no specific studies assessed the correlation between ageing and CID in COPD. Therefore, the aim of this study was to investigate the impact of ageing on CID in COPD patients.

Patients and Methods

Data obtained from 55219 COPD patients were extracted from 17 papers, mostly post-hoc analyses. A pairwise meta-analysis and a meta-regression analysis were performed according to PRISMA-P guidelines to quantify the impact of pharmacological therapy on CID and to determine whether ageing might modulate the risk of CID in COPD patients.

Results

Inhaled treatments resulted generally effective in reducing the risk of CID in COPD (relative risk: 0.81, 95% confidence interval 0.79–0.84; P < 0.001). The meta-regression analysis indicated a trend toward significance (P = 0.063) in the linear relationship between age and the risk of CID. Of note, age significantly (P < 0.05) increased the risk of CID when associated with lower post-bronchodilator FEV₁. These results were not affected by a significant risk of bias.

Conclusion

This quantitative synthesis suggests that inhaled therapy is effective in reducing the risk of CID in COPD, although such a protective effect may be affected in older patients with impaired lung function. Further studies specifically designed on CID in COPD are needed to confirm these results.

Keywords:

• ageing
• clinically important deterioration
• chronic obstructive pulmonary disease
• elderly
• meta-analysis
• inhaled therapy

Abbreviations

AB, aclidinium bromide; ADO, Age, Dyspnea and airflow Obstruction; AECOPD, acute exacerbation of COPD; ATS, American Thoracic Society; BDP, beclomethasone dipropionate; BID, bis in die, twice daily; BUD, budesonide; CAT, COPD assessment test; CI, confidence interval; CID, clinically important deterioration; COPD, chronic obstructive pulmonary disease; DECiMAL, Data Extraction for Complex Meta-anALysis; FEV₁, forced expiratory volume in the first second; FF, fluticasone furoate; FOR, formoterol fumarate; FP, fluticasone propionate; FVC, forced vital capacity; GLY, glycopyrronium bromide or glycopyrrolate; GOLD, Global Initiative for Chronic Obstructive Lung Disease; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; HRQL, health-related quality of life; ICS, inhaled corticosteroid; IND, indacaterol; LABA, long-acting β₂-adrenoceptor agonist; LAMA, long-acting muscarinic antagonist; MCID, minimal clinically important difference; mMRC, modified medical research council dyspnea scale; NA, not available; O, olodaterol; PICO, Patient problem, Intervention, Comparison, and Outcome; PCB, placebo; PMID, PubMed Identifier; PRISMA-P, Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols; PRO, patient-reported outcome; QD, quaque die, once daily; RCT, randomized controlled trial; RR, relative risk; SABA, short-acting β2-adrenoceptor agonist; SAL, salmeterol; SAMA, short-acting muscarinic antagonist; SGRQ, St. George’s Respiratory Questionnaire; T, tiotropium bromide; TDI, Transition Dyspnea Index; UMEC, umeclidinium bromide; VI, vilanterol.

Acknowlegments

No sponsor had a role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

Author Contributions

All the authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

GMM, JO and AS report no conflicts of interest in this work. MC has participated as a faculty member and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Lallemand, Mundipharma, Novartis, Pfizer, Verona Pharma, and Zambon, and is or has been a consultant to ABC Farmaceutici, AstraZeneca, Chiesi Farmaceutici, Edmond Pharma, Lallemand, Novartis, Ockham Biotech, Verona Pharma, and Zambon. His department was funded by Almirall. PR report grants and personal fees from Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, MSD, Mundipharma, and Novartis, and participated as a lecturer and advisor in scientific meetings sponsored by Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, Edmond Pharma, GlaxoSmithKline, Menarini Group, Mundipharma, and Novartis. Her department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis, and Zambon. LC participated as an advisor in scientific meetings sponsored by Boehringer Ingelheim and Novartis, received non-financial support from AstraZeneca, a research grant partially funded by Chiesi Farmaceutici, Boehringer Ingelheim, Novartis, and Almirall, and is or was a consultant to ABC Farmaceutici, MSD, Recipharm, Zambon, Verona Pharma and Ockham Biotech. His department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis and Zambon.

Additional information

Funding

This research was not funded.