In this issue of Thorax Payneet al 1 suggest that it is possible to distinguish different patterns of difficult childhood asthma by measuring exhaled NO (eNO). The knowledge that severe asthma may have different phenotypes with different types of airway inflammation is not new and has been clearly shown by bronchoalveolar lavage (BAL) and airway biopsy studies in adult patients.2The potential importance of these data lies in the classification of different patterns by using a non-invasive instantaneous measurement such as eNO.

Exhaled NO levels are known to be increased in atopic asthma, to increase during an exacerbation, to decrease with anti-inflammatory therapy,3 and to rise as the dose of inhaled steroids is reduced.4 In addition, eNO levels are correlated with eosinophils in induced sputum,5 bronchial hyperresponsiveness to AMP,6 and exercise,7and to increase in the late phase following allergen challenge.8 As a diagnostic tool, eNO levels discriminated asthmatics from non-asthmatics with a high sensitivity and specificity in a group of subjects with chronic cough.9 All the above evidence supports the contention that eNO may be considered a surrogate marker of airway inflammation in asthma.10 ,11

NO is a freely diffusible gas generated from l-arginine by NO synthases. These enzymes are found in many cells of the lung, including nerves, epithelial cells, alveolar macrophages, and other inflammatory cells. It has been suggested that the increased eNO levels found in asthmatic subjects result from an increase in the expression of inducible nitric oxide synthase 2 (NOS-2) in the respiratory tract induced by the action of proinflammatory cytokines.12Corticosteroids inhibit induction of NOS-212 ,13; however, eNO concentrations remain somewhat increased in asymptomatic patients with normal spirometric parameters, consistent with the presence of ongoing airway inflammation. Even …