Phenotypic comparison between smoking and non-smoking chronic obstructive pulmonary disease

Abstract

Background: Although COPD among non-smokers (NS-COPD) is common, little is known about this phenotype. We compared NS-COPD subjects with smoking COPD (S-COPD) patients in a rural Indian population using a variety of clinical, physiological, radiological, sputum cellular and blood biomarkers.

Methods: Two hundred ninety subjects (118 healthy, 79 S-COPD, 93 NS-COPD) performed pre- and post-bronchodilator spirometry and were followed for 2 years to study the annual rate of decline in lung function. Body plethysmography, impulse oscillometry, inspiratory-expiratory HRCT, induced sputum cellular profile and blood biomarkers were compared between 49 healthy, 45 S-COPD and 55 NS-COPD subjects using standardized methods. Spirometric response to oral corticosteroids was measured in 30 female NS-COPD patients.

Results: Compared to all male S-COPD subjects, 47% of NS-COPD subjects were female, were younger by 3.2 years, had greater body mass index, a slower rate of decline in lung function (80 vs 130 mL/year), more small airways obstruction measured by impulse oscillometry (p < 0.001), significantly less emphysema (29% vs 11%) on CT scans, lower values in lung diffusion parameters, significantly less neutrophils in induced sputum (p < 0.05) and tended to have more sputum eosinophils. Hemoglobin and red cell volume were higher and serum insulin lower in S-COPD compared to NS-COPD. Spirometric indices, symptoms and quality of life were similar between S-COPD and NS-COPD. There was no improvement in spirometry in NS-COPD patients after 2 weeks of an oral corticosteroid.

Conclusions: Compared to S-COPD, NS-COPD is seen in younger subjects with equal male-female predominance, is predominantly a small-airway disease phenotype with less emphysema, preserved lung diffusion and a slower rate of decline in lung function.

Keywords: Chronic obstructive pulmonary disease; biomass smoke; household air pollution; non-smoking COPD; small airway disease.

Fig. 1

Differences in lung function between healthy (n = 114, ●), smoking (S)-COPD (n = 71, ■),) and non-smoking COPD (n = 82, △) using (a) spirometry, with forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC) and forced expiratory flow between 75 and 25% of vital capacity (FEF_25–75); b Lung volumes, showing total lung capacity (TLC), residual volume (RV), specific airway conductance (sG_aw) and specific airway resistance (sR_aw); c Impulse oscillometry, showing resistance at 5 Hz (R5), area under the reactance curve (AX), resonant frequency (RF). Data are presented as individual data points and the bars indicate median and interquartile ranges, where * indicates p < 0.05, NS = non-significant

Fig. 2

Differences between smoker COPD (S-COPD) (n = 38) and non-smoker COPD (NS-COPD) (n = 70) on inspiratory-expiratory high resolution computerized tomography (HRCT) imaging (a) Showing HRCT classification of smoker and non-smoker COPD, including airway disease (black bars), emphysema (open bars) and interstitial lung abnormality (ILA) predominance (grey bars); (b) dot plot for emphysema and decreased attenuation of expiratory CT in S-COPD (■) and NS=COPD (△) compared to healthy subjects (●), where bars indicate median and interquartile rages and * p < 0.05, (c) Representative HRCT images of Smoker-COPD showing extensive centrilobular emphysema in the upper lobes and non-smoker COPD showing generalized decreased attenuation and some bronchial wall thickening

Fig. 3

Inflammatory cell counts in induced sputum from healthy controls (n = 27, ●), smoking (S)-COPD (n = 34, ■) and non-smoking (NS)-COPD (n = 37, △). Data are presented as individual data points and bars indicate median and interquartile ranges, * = p < 0.05, **p < 0.01

Fig. 4

Panel (a) Change in FEV₁ and FVC after 4 weeks of oral prednisolone (30 mg/day) in female non-smoking COPD patients (open bars) or placebo (black bars); data are mean values ± SEM; NS = non-significant; Panel (b) Decline in post-bronchodilator FEV₁ between healthy (n = 88), smoking COPD (n = 44) and non-smoking COPD subjects (n = 62) over 2 years