Lung function decline in asthma: association with inhaled corticosteroids, smoking and gender

Antoon Dijkstra ¹, Judith M Vonk ², Hajo Jongepier ¹, Gerard H Koppelman ¹, Jan P Schouten ², Nick HT ten Hacken ¹, Wim Timens ¹ and Dirkje S Postma ^1*

¹ University Medical Center Groningen, Netherlands
² University of Groningen, Netherlands

^* To whom correspondence should be addressed. E-mail: d.s.postma{at}int.azg.nl.

Accepted 2 November 2005

Abstract

Background:Inhaled corticosteroids (ICS) provide short-term benefits in asthma, yet long-term effects are still unknown.

Methods:We studied 281 patients diagnosed with moderate to severe asthma in 1963-1975 and re-examined them in 1991-1999. Information was collected on forced expiratory volume in 1 second (FEV₁), bronchial hyperresponsiveness, atopy, smoking, use and dosage of oral and ICS. Patients were included in the analyses if they had at least 3 FEV₁ measurements during 2 consecutive years after the age of 30, and used ICS during follow-up.

Results:Analyses were performed on 122 patients. During (median) follow-up of 23 years, 71 males and 51 females had on average 37 and 40 individual FEV₁ measurements respectively. Linear mixed effect models showed that males had (mean) 20.6 ml/year less annual FEV₁ decline after ICS initiation than before (p=0.011) and females 3.2 ml/year less decline (p=0.73). In individuals with <5 pack years smoking, males had 36.8 ml/year less FEV₁ decline (p=0.0097) after ICS institution and females 0.8 ml/year (p=0.94), difference between sexes being significant (p=0.045). These effects were not observed with 5 pack years smoking. A higher daily dose of ICS was associated with less FEV₁ decline in males (p=0.006), an effect not observed in females.

Conclusion:Treatment with ICS in our patients with moderate to severe adult asthma was associated with a reduction in FEV₁ decline over 23-year follow-up in males who had smoked less than 5 pack years at follow-up. This effect was dose-dependent and not present in females or in males with more than 5 pack years of smoking at follow-up. The absence of an ICS effect in females on FEV₁ decline needs further studies.

Keywords: asthma, dose response, inhaled corticosteroids, longitudinal, lung function decline

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