This highly volatile acid has been thought to be responsible for the acidification of EBC in stable patients with COPD and bronchiectasis.

Other mechanisms may be also important. The vesicles of macrophages and eosinophils contain vacuolar hydrogen-adenosine triphosphatase, which is responsible for an increased H+ release, and eosinophilic granules contain eosinophil peroxidase, which, in the presence of H2O2, is able to oxidize halides to form highly reactive hypohalous acids. These mechanisms could account for the relationship between disease severity and pH that we observed. However, a longitudinal study is required in children to provide more evidence of this link. The possible link between EBC pH and airway inflammation also is supported by the study of Hunt who observed a normalization of EBC pH values in asthmatic subjects after anti-inflammatory treatment in HealthCare Canadian Pharmacy.

We have observed significantly higher values of the neutrophil chemoattractant LTB4 both in children with moderate-to-severe asthma and CF than in healthy subjects. By contrast, normal levels of this marker are found in children with mild asthma. This result reflects, perhaps, different patterns of inflammation in patients with asthma of different severities, although since we did not look at airway cytology with induced sputum, this remains speculative. The presence of neutrophilic inflammation has been well-described in persons with CF, and this may account for the presence of high EBC LTB4 levels

We speculate that the correlation found between the values of EBC LTB4 and EBC pH in the control subjects, children with CF, and children with moderate and severe asthma may suggest that EBC pH is a marker of neutrophilic inflammation. However, further studies in which sputum differential cell count and measurements of other neutrophil chemoattractants, such as IL-8, are performed and correlated with EBC pH are needed to confirm this hypothesis. The fact that a correlation was observed in control subjects but not in children with mild asthma is unexplained.

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