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. 2021 Mar 15;203(6):689-698.
doi: 10.1164/rccm.202005-1854OC.

Pharmacotherapy and Lung Function Decline in Patients with Chronic Obstructive Pulmonary Disease. A Systematic Review

Bartolome R Celli  1 , Julie A Anderson  2 , Nicholas J Cowans  3 , Courtney Crim  4 , Benjamin F Hartley  3 , Fernando J Martinez  5 , Andrea N Morris  4 , Holly Quasny  4 , Julie Yates  4 , Jørgen Vestbo  6 , Peter M A Calverley  7
Affiliations

Pharmacotherapy and Lung Function Decline in Patients with Chronic Obstructive Pulmonary Disease. A Systematic Review

Bartolome R Celli et al. Am J Respir Crit Care Med. .

Abstract

Rationale: Whether pharmacological therapy alters decline in FEV1 in chronic obstructive pulmonary disease remains controversial. Because pharmacotherapy improves health status, exacerbation rate, and symptoms, it may be unethical to complete placebo-controlled long-term studies aimed at modifying FEV1 decline.Objectives: We conducted a systematic review of placebo-controlled pharmacological trials lasting ≥1 year to address the question of whether therapy alters FEV1 decline.Methods: A literature search for randomized trials that included repeated spirometry with at least one active and one placebo arm was conducted. Articles were excluded if study duration was <1 year, <3 spirometric measurements, or <100 subjects per arm. Study design was assessed using the Jadad score. To combine studies and find the estimated effect, we used random effects methodology to account for both within-study and between-study variation.Measurements and Main Results: There were 33,051 patients in the analysis (active component, n = 21,941; placebo, n = 11,110 in nine studies). The active treatment arms demonstrated a 5.0 ml/yr reduction (95% confidence interval, 0.8-9.1 ml/yr; P < 0.001) in the rate of FEV1 decline compared with the placebo arms. The relative FEV1 differences between active and placebo arms were within the range of differences reported for health status and for the exacerbation rate in the same studies.Conclusions: In chronic obstructive pulmonary disease, pharmacotherapy ameliorates rate of lung function decline. The relative benefit observed is within the range of those reported for health status and exacerbations in the same studies. Guidelines should be adjusted according to these findings.

Keywords: chronic obstructive pulmonary disease; forced expiratory volume; lung function decline; spirometry; systematic review.

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Figures

Figure 1.
Figure 1.
Flow diagram of the systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. COPD = chronic obstructive pulmonary disease.
Figure 2.
Figure 2.
Effect of all active therapies on the rate of decline in FEV1. The center of the diamond indicates the point estimate and the width is the 95% CI. BRONCUS = Bronchitis Randomized on NAC Cost-Utility Study; CI = confidence interval; COPD = chronic obstructive pulmonary disease; ISOLDE = Inhaled Steroids in Obstructive Lung Disease in Europe; LHS = Lung Health Study; LHS2 = Lung Health Study 2; SUMMIT = Study to Understand Mortality and Morbidity; TORCH = Toward a Revolution in COPD Health; UPLIFT = Understanding Potential Long-Term Impacts on Function with Tiotropium.
Figure 3.
Figure 3.
(A) Effect of ICS-containing therapies on the rate of decline in FEV1. The center of the diamond indicates the point estimate and the width is the 95% confidence interval (CI). (B) Effect of inhaled LABD therapy on the rate of decline in FEV1. The center of the diamond indicates the point estimate and the width is the 95% CI. COPD = chronic obstructive pulmonary disease; ICS = inhaled corticosteroid; ISOLDE = Inhaled Steroids in Obstructive Lung Disease in Europe; LABD = long-acting bronchodilator; LHS2 = Lung Health Study 2; SUMMIT = Study to Understand Mortality and Morbidity; TORCH = Toward a Revolution in COPD Health; UPLIFT = Understanding Potential Long-Term Impacts on Function with Tiotropium.
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Comment in

  • Rate of Decline of FEV1 as a Biomarker of Survival?
    Papi A, Beghé B, Fabbri LM. Papi A, et al. Am J Respir Crit Care Med. 2021 Mar 15;203(6):663-665. doi: 10.1164/rccm.202010-3784ED. Am J Respir Crit Care Med. 2021. PMID: 33095996 Free PMC article. No abstract available.

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