Airway responsiveness to mannitol in asthma is associated with chymase‐positive mast cells and eosinophilic airway inflammation

Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway tissue. We compared the number and phenotype of mast cells, mRNA expression of mast cell‐associated genes and number of eosinophils in airway tissue of subjects with asthma and healthy controls in relation to AHR to mannitol.

[1]  W. Henderson,et al.  Increased density of intraepithelial mast cells in patients with exercise-induced bronchoconstriction regulated through epithelially derived thymic stromal lymphopoietin and IL-33. , 2014, The Journal of allergy and clinical immunology.

[2]  L. Wood,et al.  Sputum gene expression signature of 6 biomarkers discriminates asthma inflammatory phenotypes. , 2014, The Journal of allergy and clinical immunology.

[3]  J. Ward,et al.  The relationship between eosinophilia and airway remodelling in mild asthma , 2013, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[4]  J. Bird,et al.  Mepolizumab for Severe Eosinophilic Asthma (DREAM): A Multicentre, Double-Blind, Placebo-Controlled Trial , 2013, Pediatrics.

[5]  J. Brannan,et al.  Airway Hyperresponsiveness in Asthma: Mechanisms, Clinical Significance, and Treatment , 2012, Front. Physio..

[6]  Ian D Pavord,et al.  Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial , 2012, The Lancet.

[7]  G. Nilsson,et al.  Corticosteroid treatment selectively decreases mast cells in the smooth muscle and epithelium of asthmatic bronchi , 2012, Allergy.

[8]  A. Bergqvist,et al.  Mast cell-associated alveolar inflammation in patients with atopic uncontrolled asthma. , 2011, The Journal of allergy and clinical immunology.

[9]  W. Busse,et al.  Mast cell phenotype, location, and activation in severe asthma. Data from the Severe Asthma Research Program. , 2011, American journal of respiratory and critical care medicine.

[10]  C. Porsbjerg,et al.  Airway hyperresponsiveness to mannitol and methacholine and exhaled nitric oxide: a random-sample population study. , 2010, The Journal of allergy and clinical immunology.

[11]  S. Anderson.  Indirect challenge tests: Airway hyperresponsiveness in asthma: its measurement and clinical significance. , 2010, Chest.

[12]  M. Solon,et al.  Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthma. , 2010, Journal of Allergy and Clinical Immunology.

[13]  D. Cockcroft,et al.  Direct and indirect challenges in the clinical assessment of asthma. , 2009, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[14]  K. Rabe,et al.  Pulmonary periarterial inflammation in fatal asthma , 2009, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[15]  S. Anderson,et al.  Relationship between airway responsiveness to mannitol and to methacholine and markers of airway inflammation, peak flow variability and quality of life in asthma patients , 2007, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[16]  A. Chetta,et al.  Chymase-positive mast cells play a role in the vascular component of airway remodeling in asthma. , 2007, The Journal of allergy and clinical immunology.

[17]  D. Postma,et al.  Mast cell numbers in airway smooth muscle and PC20AMP in asthma and COPD. , 2007, Respiratory medicine.

[18]  Jie Zhu,et al.  Bronchial mucosal inflammation and upregulation of CXC chemoattractants and receptors in severe exacerbations of asthma , 2007, Thorax.

[19]  J. Vernejoux,et al.  Inflammation of bronchial smooth muscle in allergic asthma , 2006, Thorax.

[20]  J. Hankinson,et al.  Standardisation of spirometry , 2005, European Respiratory Journal.

[21]  D. Robinson,et al.  Thymic Stromal Lymphopoietin Expression Is Increased in Asthmatic Airways and Correlates with Expression of Th2-Attracting Chemokines and Disease Severity1 , 2005, The Journal of Immunology.

[22]  Wei Zhao,et al.  Surface CD88 functionally distinguishes the MCTC from the MCT type of human lung mast cell. , 2005, The Journal of allergy and clinical immunology.

[23]  S. Anderson,et al.  Evidence of mast cell activation and leukotriene release after mannitol inhalation , 2003, European Respiratory Journal.

[24]  I. Pavord,et al.  Mast-cell infiltration of airway smooth muscle in asthma. , 2002, The New England journal of medicine.

[25]  S. Anderson,et al.  Budesonide reduces sensitivity and reactivity to inhaled mannitol in asthmatic subjects , 2002, Respirology.

[26]  C. Jenkins,et al.  Predictive markers of asthma exacerbation during stepwise dose reduction of inhaled corticosteroids. , 2001, American journal of respiratory and critical care medicine.

[27]  P. Gibson,et al.  Airway mast cells and eosinophils correlate with clinical severity and airway hyperresponsiveness in corticosteroid-treated asthma. , 2000, The Journal of allergy and clinical immunology.

[28]  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.

[29]  T M Mayhew,et al.  If you assume, you can make an ass out of u and me': a decade of the disector for stereological counting of particles in 3D space. , 1996, Journal of anatomy.

[30]  S. Durham,et al.  Prednisolone treatment in asthma. Reduction in the numbers of eosinophils, T cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5, and interferon-gamma cytokine gene expression within the bronchial mucosa. , 1996, American journal of respiratory and critical care medicine.

[31]  P. Howarth,et al.  Heterogeneity of human mast cells based on cytokine content. , 1995, Journal of immunology.

[32]  S. M. Goldstein,et al.  Human mast cell carboxypeptidase. Selective localization to MCTC cells. , 1991, Journal of immunology.

[33]  J. Nadel,et al.  Mast cell chymase. A potent secretagogue for airway gland serous cells. , 1989, Journal of immunology.

[34]  L. Schwartz,et al.  Quantitation of histamine, tryptase, and chymase in dispersed human T and TC mast cells. , 1987, Journal of immunology.

[35]  L. Schwartz,et al.  Two types of human mast cells that have distinct neutral protease compositions. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[36]  C. Porsbjerg,et al.  Predicting airway hyperreactivity to mannitol using exhaled nitric oxide in an unselected sample of adolescents and young adults. , 2013, Respiratory medicine.

[37]  G. Caughey.  Mast cell proteases as protective and inflammatory mediators. , 2011, Advances in experimental medicine and biology.