Am. J. Respir. Crit. Care Med., Volume 161, Number 4, April 2000, 1218-1228

Airway Nitric Oxide Diffusion in Asthma
Role in Pulmonary Function and Bronchial Responsiveness

PHILIP E. SILKOFF, JIMMIE T. SYLVESTER, NOE ZAMEL, and SOLBERT PERMUTT

Department of Medicine, The National Jewish Medical and Research Center, Denver, Colorado; The Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland; and Division of Respirology, the University of Toronto, Toronto, Ontario, Canada

If the nitric oxide (NO) diffusing capacity of the airways (DNO) is the quantity of NO diffusing per unit time into exhaled gas () divided by the difference between the concentration of NO in the airway wall (C _w) and lumen, then DNO and C_w can be estimated from the relationship between exhaled NO concentration and expiratory flow. In 10 normal subjects and 25 asthmatic patients before and after treatment with inhaled beclomethasone, DNO averaged 6.8 ± 1.2, 25.5 ± 3.8, and 22.3 ± 2.7 nl/s/ppb × 10³, respectively; C_w averaged 149 ± 31.9, 255.3 ± 46.4, and 108.3 ± 14.3 ppb, respectively; and DNOC_w (the maximal from diffusion) averaged 1,020 ± 157.5, 6,512 ± 866, and 2,416 ± 208.5 nl/s × 10³, respectively. DNO and DNOC_w in the asthmatic subjects before and after steroids were greater than in normal subjects (p < 0.0001), but C_w was not different. Within asthmatic subjects, steroids caused C_w and DNOC_w to fall (p < 0.0001), but DNO was unchanged. DNOC_w after steroids, presumably reflecting maximal diffusion of constitutive NO, was positively correlated with methacholine PC₂₀ and FEV₁/FVC before or after steroids. The increased DNO measured in asthmatic patients may reflect upregulation of nonadrenergic, noncholinergic, NO-producing nerves in airways in compensation for decreased sensitivity of airway smooth muscle to the relaxant effects of endogenous NO.

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