Weighing the evidence for pharmacological treatment interventions in mild COPD; a narrative perspective

Abstract

There is increasing focus on understanding the nature of chronic obstructive pulmonary disease (COPD) during the earlier stages. Mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 or the now-withdrawn GOLD stage 0) represents an early stage of COPD that may progress to more severe disease. This review summarises the disease burden of patients with mild COPD and discusses the evidence for treatment intervention in this subgroup.Overall, patients with mild COPD suffer a substantial disease burden that includes persistent or potentially debilitating symptoms, increased risk of exacerbations, increased healthcare utilisation, reduced exercise tolerance and physical activity, and a higher rate of lung function decline versus controls. However, the evidence for treatment efficacy in these patients is limited due to their frequent exclusion from clinical trials. Careful assessment of disease burden and the rate of disease progression in individual patients, rather than a reliance on spirometry data, may identify patients who could benefit from earlier treatment intervention.

Keywords: Chronic obstructive pulmonary disease; Corticosteroid; Early intervention.

Fig. 1

Studies reporting lung function decline in patients with mild COPD: Chen et al. [58], Bridevaux et al. [29], Brito-Mutunayagam et al. [59], Mohamed Hoesein et al. [60]. Inclusion criteria/study design: Chen et al. [58], subjects aged 45–80 years with a history of smoking or exposure to second-hand smoke for > 10 years; high-risk control group had post-bronchodilator FEV₁/FVC > 0.7 and FEV₁ < 95% predicted; mild COPD group had post-bronchodilator FEV₁/FVC < 0.7 and FEV₁ > 80% predicted in the absence of bronchodilator or inhaled corticosteroid; Bridevaux et al. [29], Swiss Study on Air Pollution and Lung Diseases in Adults cohort; considered symptomatic if chronic cough, phlegm or shortness of breath while walking reported at baseline (age range 18–60 years); Brito-Mutunayagam et al. [59], subjects aged ≥18 years from the North West Adelaide Health Study cohort; resolution, persistence or progression of GOLD stage 0 determined at 3.5-year follow-up; Mohamed Hoesin et al. [60], Dutch Belgian Lung Cancer Screening Trial; male heavy smokers (age range 47–80 years). Data shown are calculated from 3-year data described by Mohamed Hoesin et al. [60]. COPD: chronic obstructive pulmonary disease; FEV₁: forced expiratory volume in 1 s; FVC: forced vital capacity; GOLD: Global Initiative for Chronic Obstructive Lung Disease; LLN: lower limit of normal

Fig. 2

Studies reporting mortality in patients with mild COPD: Stavem et al. [61], Mannino et al. [62], Putcha et al. [63]. Inclusion criteria/study design: Stavem et al. [61], multivariate analysis of all-cause mortality over 26 years in an occupational cohort of men aged 40–59 years (data excluding all never-smokers), adjusted for age, smoking status, physical fitness, BMI, systolic blood pressure and serum cholesterol; Mannino et al. [62], multivariate analysis of all-cause mortality over 22 years in participants aged 25–74 years from the first National Health and Nutrition Examination Survey follow-up cohort, adjusted for lung function category, age, race, sex, education, smoking status, pack-years smoked, years since regularly smoked and BMI; Putcha et al. [63], all-cause mortality over 12.5 years in smokers aged 35–60 years with pre-bronchodilator FEV₁/FVC < 0.7 and FEV₁ 55–90% predicted from the Lung Health Study I and III cohorts, adjusted for age, gender, race, smoking status at Year 5, baseline FEV₁, pack-years smoked and randomisation group. BMI: body mass index; CI: confidence interval; COPD: chronic obstructive pulmonary disease; FEV₁: forced expiratory volume in 1 s; FVC: forced vital capacity; GOLD: Global Initiative for Chronic Obstructive Lung Disease; HR, hazard ratio