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Exhaled nitric oxide predicts lung function decline in difficult-to-treat asthma

Dept of ¹ Pulmonology, Medisch Spectrum Twente, Enschede, ² Dept of Pulmonology, Medical Center Leeuwarden, Leeuwarden, Depts of ³ Pulmonology, ⁵ Medical Decision Making, Leiden University Medical Center, Leiden, and ⁴ Dept of Respiratory Medicine, Academic Medical Center, Amsterdam, The Netherlands.

CORRESPONDENCE: I. H. van Veen, Dept of Pulmonology, Medisch Spectrum Twente, Postbus 50000, 7500 KA Enschede, The Netherlands. Fax: 31 534872638. E-mail: h.vanveen{at}ziekenhuis-mst.nl

Keywords: Airway obstruction, asthma, nitric oxide, severity of illness index

Received: October 15, 2007
Accepted May 7, 2008

A subset of patients with asthma is known to have progressive loss of lung function despite treatment with corticosteroids. The aim of the present study was to identify risk factors of decline in forced expiratory volume in one second (FEV₁) in patients with difficult-to-treat asthma.

In total, 136 nonsmoking patients with difficult-to-treat asthma were recruited between 1998 and 1999. Follow-up assessment was performed 5–6 yrs later in 98 patients. The predictive effect of clinical characteristics and inflammatory markers were analysed at baseline (asthma onset and duration, atopy, airway hyperresponsiveness, blood and sputum eosinophils, and the fraction of nitric oxide in exhaled air (F_eNO)) on subsequent decline in post-bronchodilator FEV₁.

Patients with high F_eNO (20 ppb) had an excess decline of 40.3 (95% confidence interval (CI) 7.3–73.2) mL·yr^–1 compared to patients with low F_eNO. F_eNO 20 ppb was associated with a relative risk of 1.9 (95% CI, 1.1–2.6) of having an accelerated (25 mL·yr^–1) decline in FEV₁. In patients with baseline FEV₁ 80% of predicted, this relationship was even stronger: 90 versus 29% had accelerated decline in FEV₁ (F_eNO 20 ppb versus F_eNO <20 ppb respectively; relative risk 3.1 (95% CI, 1.7–3.4).

Exhaled nitric oxide is a predictor of accelerated decline in lung function in patients with difficult-to-treat asthma, particularly if forced expiratory volume in one second is still normal.