Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma

BACKGROUND Airway hyperresponsiveness, induced sputum eosinophils, and exhaled nitric oxide (NO) levels have all been proposed as non-invasive markers for monitoring airway inflammation in patients with asthma. The aim of this study was to compare the changes in each of these markers following treatment with inhaled glucocorticosteroids in a single study. METHODS In a randomised, double blind, placebo controlled, parallel study 25 patients with mild asthma (19–34 years, forced expiratory volume in one second (FEV1) >75% predicted, concentration of histamine provoking a fall in FEV1 of 20% or more (PC20) <4 mg/ml) inhaled fluticasone propionate (500 μg twice daily) for four weeks. PC20 to histamine, sputum eosinophil numbers, and exhaled NO levels were determined at weeks 0, 2, and 4, and two weeks after completing treatment. Sputum was induced by inhalation of hypertonic (4.5%) saline and eosinophil counts were expressed as percentage non-squamous cells. Exhaled NO levels (ppb) were measured by chemiluminescence. RESULTS In the steroid treated group there was a significant increase in PC20, decrease in sputum eosinophils, and decrease in exhaled NO levels compared with baseline at weeks 2 and 4 of treatment. Subsequently, each of these variables showed significant worsening during the two week washout period compared with week 4. These changes were significantly different from those in the placebo group, except for the changes in sputum eosinophils and exhaled NO levels during the washout period. There were no significant correlations between the changes in the three markers in either group at any time. CONCLUSIONS Treatment of asthmatic subjects with inhaled steroids for four weeks leads to improvements in airway hyperresponsiveness to histamine, eosinophil counts in induced sputum, and exhaled nitric oxide levels. The results suggest that these markers may provide different information when monitoring anti-inflammatory treatment in asthma.

[1]  J Vestbo,et al.  A 15-year follow-up study of ventilatory function in adults with asthma. , 1998, The New England journal of medicine.

[2]  K. Chung,et al.  Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. , 1998, Thorax.

[3]  J. Drazen,et al.  Inflammation and airway function in asthma: what you see is not necessarily what you get. , 1998, American journal of respiratory and critical care medicine.

[4]  P. Sterk,et al.  Relationship between exhaled nitric oxide and airway hyperresponsiveness following experimental rhinovirus infection in asthmatic subjects. , 1998, The European respiratory journal.

[5]  P. Barnes,et al.  Exhaled and nasal nitric oxide measurements: recommendations. The European Respiratory Society Task Force. , 1997, The European respiratory journal.

[6]  P. Sterk,et al.  Comparison of inflammatory cell counts in asthma: induced sputum vs bronchoalveolar lavage and bronchial biopsies , 1997, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[7]  P. Stephenson Statement concerning the second revision of the British guidelines on asthma management , 1997 .

[8]  S. Durham,et al.  Expression of IL-4 and IL-5 mRNA and protein product by CD4+ and CD8+ T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics. , 1997, Journal of immunology.

[9]  The British Guidelines on Asthma Management1995 Review and Position Statement , 1997 .

[10]  P. Barnes,et al.  Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. , 1997, American journal of respiratory and critical care medicine.

[11]  P. Sly,et al.  Allergic respiratory disease: strategic targets for primary prevention during childhood. , 1997, Thorax.

[12]  P. Sterk,et al.  Repeatability of cellular and soluble markers of inflammation in induced sputum from patients with asthma. , 1996, The European respiratory journal.

[13]  F. Hargreave,et al.  Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. , 1996, American journal of respiratory and critical care medicine.

[14]  P. Sterk,et al.  Relationship between the inflammatory infiltrate in bronchial biopsy specimens and clinical severity of asthma in patients treated with inhaled steroids. , 1996, Thorax.

[15]  P. Barnes,et al.  Exhaled nitric oxide: a new lung function test. , 1996, Thorax.

[16]  D. Yates,et al.  Changes in the dose of inhaled steroid affect exhaled nitric oxide levels in asthmatic patients. , 1996, The European respiratory journal.

[17]  D. Yates,et al.  Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients. , 1996, American journal of respiratory and critical care medicine.

[18]  J. Stamler,et al.  Expired nitric oxide levels during treatment of acute asthma. , 1995, American journal of respiratory and critical care medicine.

[19]  S. Durham,et al.  Peripheral blood CD4 but not CD8 t-lymphocytes in patients with exacerbation of asthma transcribe and translate messenger RNA encoding cytokines which prolong eosinophil survival in the context of a Th2-type pattern: effect of glucocorticoid therapy. , 1995, American journal of respiratory cell and molecular biology.

[20]  P. Barnes,et al.  Inhaled glucocorticoids for asthma. , 1995, The New England journal of medicine.

[21]  T. Haahtela,et al.  Effects of reducing or discontinuing inhaled budesonide in patients with mild asthma. , 1994, The New England journal of medicine.

[22]  M. Calderón,et al.  Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma. , 1994, American journal of respiratory and critical care medicine.

[23]  H. Boushey,et al.  Cellular and biochemical analysis of induced sputum from asthmatic and from healthy subjects. , 1993, The American review of respiratory disease.

[24]  S. Anderson,et al.  Airway responsiveness : standardized challenge testing with pharmacological, physical and sensitizing stimuli in adults , 1993 .

[25]  J E Cotes,et al.  Lung volumes and forced ventilatory flows , 1993, European Respiratory Journal.

[26]  J E Cotes,et al.  Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. , 1993, The European respiratory journal. Supplement.

[27]  P. O'Byrne,et al.  Is nedocromil sodium effective treatment for asthma? , 1993, The European respiratory journal.

[28]  Z. Tomori,et al.  Comparison of inspiratory effort in sniff-like aspiration reflex, gasping and normal breathing in cats. , 1993, The European respiratory journal.

[29]  T. Lee,et al.  Glucocorticoids inhibit granulocyte-macrophage colony-stimulating factor-1 and interleukin-5 enhanced in vitro survival of human eosinophils. , 1992, Immunology.

[30]  H. Kita,et al.  Glucocorticoids inhibit cytokine-mediated eosinophil survival. , 1991, Journal of immunology.

[31]  S. Moncada,et al.  Nitric oxide: physiology, pathophysiology, and pharmacology. , 1991, Pharmacological reviews.

[32]  R. Djukanović,et al.  Mucosal inflammation in asthma. , 1990, The American review of respiratory disease.

[33]  H. Sluiter,et al.  Changes in bronchial hyperreactivity induced by 4 weeks of treatment with antiasthmatic drugs in patients with allergic asthma: a comparison between budesonide and terbutaline. , 1985, The Journal of allergy and clinical immunology.