Alveolar nitric oxide in adults with asthma: evidence of distal lung inflammation in refractory asthma

Abstract

Recent studies have suggested that alveolar nitric oxide (NO) concentration is a noninvasive test of distal lung inflammation.The current study determined whether alveolar NO concentration can be measured in patients with asthma of varying severity, tested the hypothesis that there is an association between alveolar NO and bronchoalveolar lavage (BAL) eosinophil count and determined whether refractory asthma is characterised by a raised alveolar NO concentration. Finally, the present authors assessed the effect of 2 weeks of prednisolone (30 mg q.d.) on alveolar NO concentration.Alveolar NO concentration was both measurable and repeatable in patients with refractory asthma. A positive correlation was found between alveolar NO concentration and BAL eosinophil count but not with bronchial wash or sputum eosinophil count. Alveolar NO concentration was increased in patients with refractory asthma (7.1 ppb) compared with mildto-moderate asthma (3.4 ppb) and normal controls (3.4 ppb) and reduced by treatment with prednisolone.In conclusion, these findings support the hypothesis that alveolar nitric oxide is a measure of distal airway inflammation and suggest that distal lung inflammation is present in refractory asthma.

Biomarkers in asthma and allergic rhinitis

“…Alternatively, if measured at multiple expired flow rates, eNO can be portioned into NO from the central bronchial parts versus NO from the more peripheral (alveolar) compartment. It has already been demonstrated that alveolar NO is increased in severe asthma in comparison with mild to moderate persistent asthma, while there is no difference in eNO between the latter groups [134]. In the same study it was also shown that alveolar NO is refractory to inhaled corticosteroids, but responsive (i.e.…”

iNOS affects matrix production in distal lung fibroblasts from patients with mild asthma

“…Asthmatic patients, uncontrolled on standard ICS therapy, have been shown to have increased alveolar NO levels (19,28,29). Increased alveolar NO may indicate a greater risk for asthma deterioration with nocturnal awakening (30) and risk for exacerbations and increased annual decline in lung function (31,32). It is thus plausible to assume that nitric oxide in the peripheral airways is involved in the process of airway inflammation and remodelling, associated with different mechanisms compared to more central airways.…”

Assessing and accessing the small airways; implications for asthma management

“…In a study by Carroll et al [19], the increased expression of mast cell chymase in the outer area of the distal airways was significantly associated with impaired lung function in individuals with severe asthma. In subjects with severe asthma compared with those with mild to moderate asthma, an increased production of alveolar nitric oxide (NO), but not bronchial NO, was also found [20], implying that a more intense degree of inflammation occurs in the periphery of the bronchial tree in the most severe forms of asthma.…”

“…The detection of alveolar NO is associated with nocturnal asthma, symptomatic asthmatics and asthmatics with more severe disease [8,52]. Moreover, alveolar NO is more sensitive to oral than to inhaled corticosteroids, suggesting that it may represent true abnormalities of peripheral airways, which are better reached by systemic drugs than by conventional inhaled formulations [20]. More recently, a method of monitoring the daily fluctuations in FeNO values with quantification over a period of time has been established, providing information on a subject's asthma severity with regard to asthma control and exacerbation risk [53].…”