Early ReportBronchodilator S-nitrosothiol deficiency in asthmatic respiratory failure
Introduction
Nitric oxide (NO) is present in expired air. Concentrations of NO are higher in asthmatic children and in adults.1 Human airways also contain NO-adduct compounds called S-nitrosothiols (SNOs). These have a broad range of bioactivities, including bronchodilatation, receptor-mediated neurotransmission, and host defence,2, 3, 4, 5, 6 and their synthesis or breakdown may be regulated.7, 9, 10, 11, 12, 13, 14 Airway concentrations of both NO and S-nitrosothiols are believed to reflect inducible (inflammatory) nitric oxide synthase expression, which is increased in asthmatic patients.8 However, S-nitrosothiol concentrations have not been measured in individuals with asthma. We report that asthmatic respiratory failure is paradoxically associated with low airway concentrations of S-nitrosothiols. This finding suggests that previously unrecognised disorders of S-nitrosothiol metabolism may be associated with life-threatening asthma.
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Patients and methods
Asthmatic children in respiratory failure were studied within 24 h of endotracheal intubation. Asthma was defined as: a history of three or more albuterol-responsive episodes of expiratory-flow limitation; an inspiratory-time to expiratory-time ratio of less than 0·33; and no evidence of pneumonia. Control children had no history of respiratory disease and were undergoing elective non-thoracic surgery (table).2 Aspirates from three additional children (mean age 6·4 [SD 5·5] years) who were
Results
The airway S-nitrosothiol concentrations of asthmatic children were substantially lower than those of normal children (65 [SD 45] nmol/L, n=8 vs 502 [SD 429] nmol/L, n=21; figure) as measured by photolysis signals and verified with the CuCl method in four children. In two children with asthma for whom adequate samples were available for ultrafiltration, low-mass S-nitrosothiols (< 10 kDa) comprised more than 90% of total S-nitrosothiols—a finding that is consistent with previous research on
Discussion
Near-fatal asthma is associated with a deficiency of S-nitrosothiols, endogenous bronchodilators which are over 100-fold more potent than theophylline.2, 3, 5 This observation raises the possibility that depletion of bronchodilator S-nitrosothiols may contribute to the pathophysiology of severe airflow obstruction. This is an unexpected finding, since severe asthma is classically characterised by an excess of bronchoconstricting and inflammatory mediators—not by a bronchodilator deficiency.
To
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