Exhaled markers in the monitoring of airways inflammation and its response to steroid's treatment in mild persistent asthma.

The measure of inflammatory cytokines in the exhaled breath condensate has been recently proposed for use in monitoring asthma and the therapeutic response to steroids. The aim of the present study was to investigate the usefulness of measuring exhaled IL-6, IL-4 and pH in mild persistent asthma. Furthermore the effects on these markers of inhaled steroids were assessed. The study enrolled 28 asthmatic (15 males, 38+/-12 years) and 15 healthy subjects (5 males, 35+/-6 years). IL-6, IL-4 and pH were measured in the exhaled breath condensate of the subjects studied. Significantly higher concentrations of IL-6 and IL-4 were observed in the breath condensate of asthmatic patients (7.1+/-1.1 and 64.4+/-8.3 pg/ml) compared to controls (2.7+/-0.6 and 31.7+/-3.5 pg/ml), p<0.001. Furthermore, exhaled IL-4 fell significantly after treatment with inhaled steroids for 6 months (47.9+/-3.2 pg/ml, p<0.001) while exhaled IL-6 did not (6.4+/-1.0 pg/ml, p=0.8). The exhaled pH turned out to be lower in asthmatic subjects than in controls (7.39+/-0.11 vs. 7.85+/-0.14; P<0.001) but trended towards control levels after steroid treatment (7.65+/-0.16, P<0.001). We conclude that the measurement of exhaled IL-4 and pH in mild asthmatic subjects could be a useful way of monitoring their airway inflammation as well as their response to the treatment.

[1]  E. Mutius,et al.  Presentation of new GINA guidelines for paediatrics. The Global Initiative on Asthma. , 2000 .

[2]  Y. Koh,et al.  Relationship between changes in interferon‐γ production by peripheral blood T cells and changes in peak expiratory flow rate in patients with chronic stable asthma , 2002, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[3]  L. Boulet,et al.  Asymptomatic airway hyperresponsiveness: relationships with airway inflammation and remodelling. , 1999, The European respiratory journal.

[4]  C. Wong,et al.  Proinflammatory cytokines (IL‐17, IL‐6, IL‐18 and IL‐12) and Th cytokines (IFN‐γ, IL‐4, IL‐10 and IL‐13) in patients with allergic asthma , 2001, Clinical and experimental immunology.

[5]  H. Lee,et al.  Serum Levels of Interleukins (IL)-4, IL-5, IL-13, and Interferon-γ in Acute Asthma , 2001 .

[6]  M. Segal,et al.  Relationship between airway inflammation, hyperresponsiveness, and obstruction in asthma. , 2001, The Journal of allergy and clinical immunology.

[7]  P. Barnes,et al.  Increased inflammatory markers in the exhaled breath condensate of cigarette smokers , 2003, European Respiratory Journal.

[8]  M. Humbert,et al.  Severe pulmonary hypertension in histiocytosis X. , 2000, American journal of respiratory and critical care medicine.

[9]  C. Jenkins,et al.  Effect of prednisone and beclomethasone dipropionate on airway responsiveness in asthma: a comparative study. , 1988, Thorax.

[10]  I. Pavord,et al.  Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids , 2002, Thorax.

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

[12]  M. C. Liu,et al.  Analysis of cytokine transcripts in the bronchoalveolar lavage cells of patients with asthma. , 1993, American journal of respiratory cell and molecular biology.

[13]  J. Vandenbroucke,et al.  Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. The AMPUL Study Group. , 1999, American journal of respiratory and critical care medicine.

[14]  F. Hargreave,et al.  Sputum in severe exacerbations of asthma: kinetics of inflammatory indices after prednisone treatment. , 1997, American journal of respiratory and critical care medicine.

[15]  B. Gaston,et al.  Endogenous airway acidification. Implications for asthma pathophysiology. , 2000, American journal of respiratory and critical care medicine.

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

[17]  E. Eber,et al.  Serum eosinophil cationic protein and bronchial responsiveness in pediatric and adolescent asthma patients. , 1999, Chest.

[18]  A. Frew,et al.  Position Paper: Allergen standardization and skin tests , 1993 .

[19]  H. Kerstjens,et al.  Accuracy of eosinophils and eosinophil cationic protein to predict steroid improvement in asthma , 2002, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[20]  S. Kudoh,et al.  INHALATION OF DIESEL EXHAUST FOR THREE MONTHS AFFECTS MAJOR CYTOKINE EXPRESSION AND INDUCES BRONCHUS-ASSOCIATED LYMPHOID TISSUE FORMATION IN MURINE LUNGS , 2003, Experimental lung research.

[21]  K. Shirato,et al.  Baseline airway hyperresponsiveness and its reversible component: role of airway inflammation and airway calibre. , 2000, The European respiratory journal.

[22]  John Rees,et al.  ABC of Asthma , 1984 .

[23]  D. Postma,et al.  Interleukin‐6 promotes the production of interleukin‐4 and interleukin‐5 by interleukin‐2‐dependent and ‐independent mechanisms in freshly isolated human T cells , 2002, Immunology.

[24]  P. Foster,et al.  Integrated Signals Between IL-13, IL-4, and IL-5 Regulate Airways Hyperreactivity , 2000, The Journal of Immunology.

[25]  P. Foster,et al.  Chemokines in asthma: cooperative interaction between chemokines and IL-13. , 2003, The Journal of allergy and clinical immunology.

[26]  M. Tsukino,et al.  Changes in Indices of Airway Hyperresponsiveness During One Year of Treatment with Inhaled Corticosteroids in Patients with Asthma , 2001, The Journal of asthma : official journal of the Association for the Care of Asthma.

[27]  D. Altman,et al.  Statistics notes: Measurement error , 1996 .

[28]  P. Brand,et al.  Peak flow variation in childhood asthma: correlation with symptoms, airways obstruction, and hyperresponsiveness during long term treatment with inhaled corticosteroids , 1999, Thorax.

[29]  Y. Sai,et al.  The role of vacuolar H(+)-ATPase in the control of intragranular pH and exocytosis in eosinophils. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[30]  Yuan-jue Zhu,et al.  Pathogenesis of cigarette smoke-induced chronic obstructive pulmonary disease and therapeutic effects of glucocorticoids and N-acetylcysteine in rats. , 2004, Chinese medical journal.

[31]  Giovanna E Carpagnano,et al.  Increased leukotriene B4 and interleukin-6 in exhaled breath condensate in cystic fibrosis. , 2003, American journal of respiratory and critical care medicine.

[32]  O. Kalayci,et al.  Increased Interleukin-4 and Decreased Interferon Gamma Production in Children with Asthma: Function of Atopy or Asthma? , 2002, The Journal of asthma : official journal of the Association for the Care of Asthma.

[33]  K. Chida,et al.  Th1/Th2 profile in peripheral blood in atopic cough and atopic asthma , 2003, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[34]  T. Płusa,et al.  Cellular and cytokine immunoregulation in patients with chronic obstructive pulmonary disease and bronchial asthma. , 2002, Mediators of inflammation.

[35]  P. Barnes,et al.  Increased nitrotyrosine in exhaled breath condensate of patients with asthma. , 2000, American journal of respiratory and critical care medicine.

[36]  M. Tuchinda,et al.  Diagnostic significance of pH, lactic acid dehydrogenase, lactate and glucose in pleural fluid. , 1979, Respiration; international review of thoracic diseases.

[37]  S. Holgate,et al.  Effect of regular inhaled beclomethasone on exercise and methacholine airway responses in school children with recurrent wheeze. , 1995, The European respiratory journal.

[38]  P. Barnes,et al.  Increased 8-isoprostane and interleukin-6 in breath condensate of obstructive sleep apnea patients. , 2002, Chest.

[39]  H. Boezen,et al.  Clinical and immunologic factors associated with the presence or absence of airways hyper‐responsiveness in childhood asthma , 2002, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

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

[41]  Konstantinos Kostikas,et al.  pH in expired breath condensate of patients with inflammatory airway diseases. , 2002, American journal of respiratory and critical care medicine.

[42]  S. Nishima,et al.  Exhaled Nitric Oxide as a Simple Assessment of Airway Hyperresponsiveness in Bronchial Asthma and Chronic Cough Patients , 2003, The Journal of asthma : official journal of the Association for the Care of Asthma.

[43]  P. Barnes,et al.  Increased interleukin-4 and decreased interferon-gamma in exhaled breath condensate of children with asthma. , 2002, American journal of respiratory and critical care medicine.