Determinants of lung function decline in adult asthma. Results from the European Community Respiratory Health Survey

Introduction Forced expiratory volume in 1 second (FEV1) is a predictor of mortality in the general, as well as in the asthmatic population. Subjects with asthma have a steeper decline in FEV1 over time than subjects without, and some patients with severe asthma develop progressive airflow obstruction that is not fully reversible with currently available therapy. Moreover, a FEV1 lower than predicted is a marker of poor asthma control. Aims This thesis was aimed at shedding some light on the factors associated with the decline in FEV1 in subjects with asthma, with particular attention paid to investigating the potential preventative effect of the use of inhaled corticosteroids (ICSs), as well as to the association of FEV1 decline with body mass index (BMI) and change in body weight over time. Methods We analysed data from an international, population-based cohort of subjects with asthma, identified in the European Community Respiratory Health Survey (ECRHS, 1991-1993) and followed up from 1999 to 2002. Spirometry was performed on both occasions, and FEV1 decline was related to potential determinants evaluated at baseline and during the follow-up by random intercept linear regression models. Results In asthmatic subjects with high (>100 kU/L) immunoglobulin E (IgE), the use of ICSs for 4 years or more during the follow-up was associated with a lower FEV1 decline (23 mL/y; 95% CI: 8-38 compared with non-users). This association was not seen in asthmatic subjects with lower IgE. In asthmatic subjects who did not have airflow obstruction (FEV1/FVC<0.70) at baseline, obese subjects had the lowest level of FEV1 at baseline; a faster FEV1 decline was observed for subjects with intermediate BMI than for lean and obese subjects; FEV1 decline was associated with weight gain independently of baseline BMI, and this association was stronger in men (20, 95% CI: 10; 30, mL/year per kg gained) than in women (7, 95% CI: 2; 11, mL/year); these figures were about 60% greater than the decline found in men and women from the general population who took part in the ECRHS. In asthmatic subjects with airflow obstruction at baseline, the absence of allergen sensitization and a low BMI at baseline were associated with a faster FEV1 decline, while weight gain was not associated with decline. Conclusions and clinical implications Our findings confirm the beneficial association between long-term treatment with ICSs and lung function decline in asthma. However, they suggest that asthmatic subjects with high IgE could maximally benefit from prolonged treatment with ICSs. As a consequence, it could be worth calibrating the corticosteroid dose according to a patient’s level of total IgE, although further studies are needed to clarify this. The detrimental effect of weight gain on FEV1 decline is particularly important in asthmatic subjects who still do not have an established airflow obstruction. This effect could be greater in subjects with asthma than in people from the general population. Accordingly, weight management in asthma and weight loss in overweight or obese asthmatic individuals are strongly recommended. Among asthmatic subjects with airflow obstruction at baseline, lean subjects without sensitization to allergens deserve particular attention, because they had the greatest decline in FEV1. Weight gain was not associated with decline, suggesting that mechanisms that are typical of milder asthma could be less important in severe asthma, while a serious long-lasting inflammation may have a crucial role.