I want to thank Drs Mahut and Delclaux for their interesting letter concerning our recent paper1 and would offer the following response. During acute asthma exacerbation only two of 15 patients with asthma (13%) had a combined abnormally elevated central airways nitric oxide (NO) flux and elevated peripheral airway/alveolar NO concentration after correction for NO axial back-diffusion. Central airways NO flux remained the major site of ‘NO-mediated inflammation’ in 13 of 15 patients with asthma since two had normal NO gas exchange despite acute exacerbation.1 This latter observation needs to be further investigated since the clinical response was similar to that in patients with asthma with abnormal NO gas exchange. Many years ago we investigated the simplified detection of peripheral airway disease and showed that analyses of the distal part of the maximum expiratory flow–volume curve were helpful.2 However, in a subsequent study3 we reported that, if the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV₁/FVC) was ≥75%, the occurrence of an isolated abnormal mid forced expiratory flow (FEF_25–75) was rare. However, if the FEV₁/FVC was <75%, it would not be unusual to find an abnormal FEF_25–75, but it would not discriminate peripheral from large central airways obstruction.3 I hope these comments are helpful and appreciate their interest.