Upper and lower airway nitric oxide levels in primary ciliary dyskinesia, cystic fibrosis and asthma
Patients with primary ciliary dyskinesia (PCD) have abnormal ciliary function and low nitric oxide levels. Nitric oxide (NO) biosynthesis is dependent on nitric oxide synthases (NOS). Cilia line the bronchial but not the alveolar epithelium. It has been hypothesised that NOS function relies on normal ciliary function and that in PCD bronchial but not alveolar NO might therefore be reduced. The aim of this study was to assess bronchial and alveolar NO levels primarily comparing healthy children to PCD and secondarily to cystic fibrosis (CF) and asthmatic children. Multiple flow-rate fractional exhaled and nasal NO measurements were performed using a NIOX(®) Flex NO analyser (Aerocrine, Sweden) in children with PCD (n = 14), asthma (n = 18), CF (n = 12) and healthy controls (n = 18). Alveolar and bronchial NO levels were derived using a model of pulmonary NO exchange-dynamics. Both the bronchial and alveolar NO were significantly lower in PCD than healthy controls (mean (SD) 264 (209) picolitres/second (pl/s) vs. 720 (514) pl/s, p = 0.024 and 1.7 (0.8) parts per billion (ppb) vs. 3.5 (1.3) ppb, p = 0.001 respectively.) In asthmatics bronchial NO was found to be significantly higher than in healthy controls and in children with CF alveolar NO was significantly lower (2100 (1935) pl/s, p = 0.045 and 2.5 (1.2) ppb, p = 0.034 respectively.) Our findings do not support the hypothesis that NOS and ciliary function are coupled instead suggesting a more generalised mechanism for the low levels of NO seen in PCD. Our findings in CF and asthma corroborate evidence that these are diseases of the lung peripheries and bronchi respectively.