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Formoterol Attenuates Neutrophilic Airway Inflammation in Asthma^*

Kittipong Maneechotesuwan, MD; Sarah Essilfie-Quaye, BSc; Sally Meah; Claire Kelly; Sergei A. Kharitonov, MD, PhD; Ian M. Adcock, PhD and Peter J. Barnes, MA, DM, DSc

^* From the Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, London, UK. Current address: Division of Respiratory Disease and Tuberculosis, Department of Internal Medicine, Siriraj Hospital, Mahidol University, Thailand.

Correspondence to: Peter J. Barnes, MD, Department of Thoracic Medicine, Dovehouse St, London, SW3 6LY, UK; e-mail: p.j.barnes{at}imperial.ac.uk

Study objectives: Airway neutrophil levels are increased in patients with severe asthma and during asthma exacerbations. Long-acting ß₂-agonists (LABAs), such as formoterol, reduce the number of asthma exacerbations. While ß₂-agonists may affect neutrophil function in vitro, it is uncertain whether they have effects on neutrophilic inflammation in asthmatic patients in vivo.

Design: In a double-blind randomized crossover study, we evaluated the effects of 4 weeks of treatment with formoterol (Turbuhaler), 24 µg bid, compared to placebo on sputum neutrophil numbers and interleukin (IL)-8 levels in asthmatic patients. Therapy with budesonide (administered via Turbuhaler), 400 µg bid for 4 weeks, was added at the end as a "gold standard" antiinflammatory effect comparison.

Patients: We studied 15 steroid-naïve nonsmoking patients who ranged from 19 to 51 years of age and had mild persistent asthma.

Results: Formoterol therapy significantly reduced sputum IL-8 levels and neutrophil numbers compared to placebo. There was a significant correlation between the reduction in sputum IL-8 levels and the number of neutrophils, indicating that formoterol may attenuate neutrophilic airway inflammation by inhibiting IL-8 production.

Conclusions: Our data suggest that the LABA formoterol reduces neutrophilic airway inflammation in patients with mild asthma and that this might be beneficial in preventing asthma exacerbations.

Key Words: asthma • formoterol • interleukin-8 • long-acting ß₂-agonist • neutrophil

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