Markers of airway inflammation and airway hyperresponsiveness in patients with well-controlled asthma.

In steroid-naive asthmatics, airway hyperresponsiveness correlates with noninvasive markers of airway inflammation. Whether this is also true in steroid-treated asthmatics, is unknown. In 31 stable asthmatics (mean age 45.4 yrs, range 22-69; 17 females) taking a median dose of 1,000 microg inhaled corticosteroids (ICS) per day (range 100-3,600 microg x day(-1)), airway responsiveness to the "direct" agent histamine and to the "indirect" agent mannitol, lung function (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF)), exhaled nitric oxide (eNO), and number of inflammatory cells in induced sputum as a percentage of total cell count were measured. Of the 31 subjects, 16 were hyperresponsive to mannitol and 11 to histamine. The dose-response ratio (DRR: % fall in FEV1/cumulative dose) to both challenge tests was correlated (r=0.59, p=0.0004). However, DRR for histamine and DRR for mannitol were not related to basic lung function, eNO, per cent sputum eosinophils and ICS dose. In addition, NO was not related to basic lung function and per cent sputum eosinophils. In clinically well-controlled asthmatics taking inhaled corticosteroids, there is no relationship between markers of airway inflammation (such as exhaled nitric oxide and sputum eosinophils) and airway responsiveness to either direct (histamine) or indirect (mannitol) challenge. Airway hyperresponsiveness in clinically well-controlled asthmatics appears to be independent of eosinophilic airway inflammation.

[1]  S. Anderson,et al.  Nedocromil sodium inhibits responsiveness to inhaled mannitol in asthmatic subjects. , 2000, American journal of respiratory and critical care medicine.

[2]  P. Gibson,et al.  Induced sputum eosinophils in the assessment of asthma and chronic cough* , 2000, Respirology.

[3]  K. Chung,et al.  Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in mild to moderately severe asthma , 2000, Thorax.

[4]  A. Zwinderman,et al.  Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma , 1999, Thorax.

[5]  F. Hargreave,et al.  Induced sputum for the investigation of airway inflammation: evidence for its clinical application. , 1999, Canadian respiratory journal.

[6]  Nathan J. Brown,et al.  Exhaled nitric oxide measurements in a population sample of young adults. , 1999, American journal of respiratory and critical care medicine.

[7]  P. Barnes,et al.  Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma , 1999, Thorax.

[8]  R. Pellegrino,et al.  Airway hyperresponsiveness in asthma: not just a matter of airway inflammation , 1998, Thorax.

[9]  A. Cripps,et al.  Epidemiological association of airway inflammation with asthma symptoms and airway hyperresponsiveness in childhood. , 1998, American journal of respiratory and critical care medicine.

[10]  P. Gibson,et al.  Persistence of sputum eosinophilia in children with controlled asthma when compared with healthy children. , 1998, The European respiratory journal.

[11]  G. Verleden,et al.  Exhaled nitric oxide correlates with airway hyperresponsiveness in steroid-naive patients with mild asthma. , 1998, American journal of respiratory and critical care medicine.

[12]  J. Kips,et al.  Methods for sputum induction and analysis of induced sputum: a method for assessing airway inflammation in asthma. , 1998, The European respiratory journal. Supplement.

[13]  W. Busse,et al.  Efficacy and safety of inhaled corticosteroids. New developments. , 1998, American journal of respiratory and critical care medicine.

[14]  P. Barnes,et al.  Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. , 1998, Thorax.

[15]  S. Anderson,et al.  The effect of inhaling a dry powder of sodium chloride on the airways of asthmatic subjects. , 1997, The European respiratory journal.

[16]  S. Anderson,et al.  A new method for bronchial-provocation testing in asthmatic subjects using a dry powder of mannitol. , 1997, American journal of respiratory and critical care medicine.

[17]  D. Postma,et al.  Peak flow variation in childhood asthma: relationship to symptoms, atopy, airways obstruction and hyperresponsiveness. Dutch CNSLD Study Group. , 1997, The European respiratory journal.

[18]  I. Pavord,et al.  The use of induced sputum to investigate airway inflammation. , 1997, Thorax.

[19]  F. Hargreave,et al.  Measurement of inflammatory indices in induced sputum: effects of selection of sputum to minimize salivary contamination. , 1996, The European respiratory journal.

[20]  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.

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

[22]  E. Walters,et al.  Effect of high dose inhaled fluticasone propionate on airway inflammation in asthma. , 1995, American journal of respiratory and critical care medicine.

[23]  C. Salome,et al.  Which index of peak expiratory flow is most useful in the management of stable asthma? , 1995, American journal of respiratory and critical care medicine.

[24]  G. Guyatt,et al.  A research method to induce and examine a mild exacerbation of asthma by withdrawal of inhaled corticosteroid , 1992, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

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

[26]  J. Denburg,et al.  Use of induced sputum cell counts to investigate airway inflammation in asthma. , 1992, Thorax.

[27]  C. Salome,et al.  Relation of dose-response slope to respiratory symptoms in a population of Australian schoolchildren. , 1991, The American review of respiratory disease.

[28]  M. Segal,et al.  Analysis of dose-response curves to methacholine. An approach suitable for population studies. , 1987, The American review of respiratory disease.

[29]  J Britton,et al.  Histamine challenge testing: comparison of three methods. , 1986, Thorax.

[30]  A. Woolcock,et al.  Rapid method for measurement of bronchial responsiveness. , 1983, Thorax.

[31]  M. Lebowitz,et al.  Changes in the normal maximal expiratory flow-volume curve with growth and aging. , 1983, The American review of respiratory disease.

[32]  John W. Wilson,et al.  Asthma Management Handbook , 2002 .

[33]  V. Brusasco,et al.  Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma. , 1998, American journal of respiratory and critical care medicine.

[34]  J. Kips,et al.  Position paper on methods for sputum induction and analysis of induced sputum as a method for assessing airway inflammation in asthma. European Respiratory Society Task Force , 1998 .

[35]  C. Jenkins,et al.  Airway responsiveness in asthma: bronchial challenge with histamine and 4.5% sodium chloride before and after budesonide. , 1997, Allergy and asthma proceedings.

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

[37]  B. Make,et al.  Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Thoracic Society. , 1995, American journal of respiratory and critical care medicine.

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

[39]  Phillips Yy,et al.  Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, November 1986. , 1987, The American review of respiratory disease.