Elsevier

The Lancet

Volume 351, Issue 9112, 2 May 1998, Pages 1317-1319
The Lancet

Early Report
Bronchodilator S-nitrosothiol deficiency in asthmatic respiratory failure

https://doi.org/10.1016/S0140-6736(97)07485-0Get rights and content

Summary

Background

Nitric oxide (NO) gas concentrations are high in the expired air of individuals with asthma, but not consistently so in the expired air of people with pneumonia. S-nitrosothiols are naturally occurring bronchodilators, the concentrations of which are raised in the airways of patients with pneumonia. Airway S-nitrosothiols have not been studied in asthma.

Methods

Tracheal S-nitrosothiol concentrations from eight asthmatic children in respiratory failure were compared with those of 21 children undergoing elective surgery.

Results

Mean S-nitrosothiol concentrations in asthmatic children were lower than in normal children (65 [SD 45] nmol/L vs 502 [SD 429] nmol/L) and did not vary with inspired oxygen concentration or airway thiol concentration.

Interpretation

Severe asthma is associated with low concentrations of airway S-nitrosothiols. This is the first reported deficiency of an endogenous bronchodilator in the human asthmatic airway lining fluid. We suggest that S-nitrosothiol metabolism may be a target for the development of new asthma therapies.

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.

Section snippets

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

References (27)

  • B Gaston et al.

    Endogenous nitrogen oxides and bronchodilator S-nitrosothiol in human airways

    Proc Natl Acad Sci USA

    (1993)
  • B Gaston et al.

    Relaxation of human bronchial smooth muscle by S-nitrosothiols in vitro

    J Pharmacol Exp Ther

    (1994)
  • JS Stamler

    Redox signaling: nitrosylation and related target interactions of nitric oxide

    Cell

    (1997)
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