ASTHMA

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

A Dijkstra^1,2, J M Vonk³, H Jongepier^1,2, G H Koppelman⁴, J P Schouten³, N H T ten Hacken², W Timens⁵, D S Postma²

¹ Department of Pulmonary Rehabilitation, Beatrixoord, Haren, University Medical Center and University of Groningen, the Netherlands
² Department of Pulmonology, University Medical Center and University of Groningen, the Netherlands
³ Department of Epidemiology and Statistics, University Medical Center and University of Groningen, the Netherlands
⁴ Beatrix Children’s Hospital, University Medical Center and University of Groningen, the Netherlands
⁵ Department of Pathology and Laboratory Medicine, University Medical Center and University of Groningen, the Netherlands

Correspondence to:
Dr D S Postma
Department of Pulmonology, University Medical Center Groningen, Hanzeplein 1, P O Box 30.001, 9700 RB Groningen, The Netherlands; d.s.postma{at}int.umcg.nl

Background: Inhaled corticosteroids (ICS) provide short term benefits in asthma but the long term effects are still unknown.

Methods: 281 patients diagnosed with moderate to severe asthma in 1963–75 were re-examined in 1991–9. 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 three FEV₁ measurements during two consecutive years after the age of 30 and used ICS during follow up.

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

Conclusion: Treatment with ICS in adult patients with moderate to severe asthma was associated with a reduction in the decline in FEV₁ over a 23 year follow up period in men who had smoked <5 pack years. This effect was dose dependent and was not present in women or in men with 5 pack years of smoking at follow up. The lack of effect of ICS on the decline in FEV₁ in women needs further study.

Keywords: asthma; lung function decline; inhaled corticosteroids; smoking; sex

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