Introduction and objectives The airflow limitation of COPD results from small airway disease and emphysema. These phenotypes are likely to have independent genetic risk factors. It is not known if the heterogeneity of COPD accounts for the relatively weak association between pack-years smoked and forced expiratory volume in 1 s (FEV1) seen within smoking populations, or bronchodilator response (BDR). This study aimed to assess the effect of these phenotypes on the association between smoking and FEV1 and on BDR.
Method The international COPD genetics network is a multi-centre study aimed at identifying genes that predispose to COPD, in which high resolution computed tomography (HRCT) was used to quantify components of the COPD phenotype: (i) emphysema detected by radiologists (RE), (ii) emphysema assessed as per cent low-attenuation area (%LAA) and (iii) airway wall thickness (AWT) for airways with an internal perimeter of 10 mm (Pi10), 20 mm (Pi20), and average per cent wall area (WA%). They were then assessed for their effect on the association between smoking and lung function (FEV1% predicted (FEV1%)), and on BDR.
Results RE data were available for 1159 individuals, 745 had complete data for Pi10, Pi20, AWT% and %LAA. The association between pack-years smoked and FEV1% was greater in those without (r=−0.41), compared to those with, RE (r=−0.12, p<0.001 for difference in effect). AWT and RE correlated with FEV1% but had different relationships with smoking; AWT was positively associated with pack-years but there was no relationship between RE severity and pack-years smoked. RE, %LAA and AWT made independent contributions to FEV1%. Post-bronchodilator increase in FEV1 was inversely associated with severity of RE (Abstract S113 Table 1), even after adjustment for pre-bronchodilator FEV1 (p<0.01). BDR was also inversely associated with %LAA (p=0.02, and p≤0.05 adjusted for baseline FEV1).
Conclusion The AWT component of COPD, but not the severity of RE, increases with pack-years smoked, and the association between pack-years and FEV1% is greatest in those with an airway predominant phenotype. This suggests different gene-smoking interactions between phenotypes. RE and %LAA independently contribute to FEV1% and therefore measure different components of emphysema, however both were inversely associated with BDR.
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