Asthma, rhinitis, other respiratory diseases
Airway mast cells and eosinophils correlate with clinical severity and airway hyperresponsiveness in corticosteroid-treated asthma,☆☆

https://doi.org/10.1067/mai.2000.105319Get rights and content

Abstract

Background: The relationship between airway inflammation and asthma severity in corticosteroid-treated asthma is unclear. Objectives: Our purpose was to characterize the inflammatory cell profile of the airway lumen and epithelium in corticosteroid-treated asthma and to relate these findings to clinical and physiologic markers of asthma severity. Methods: Adults (n = 20) with asthma received standardized high-dose inhaled corticosteroid therapy with beclomethasone 2000 μg per day for 8 weeks. Airway responsiveness to methacholine and hypertonic (4.5%) saline solution was then assessed, followed by sputum induction and, 1 week later, bronchoscopy with bronchoalveolar lavage and bronchial brush biopsy to assess inflammatory cells. Results: Clinical asthma severity was associated with airway hyperresponsiveness. Metachromatic cells were the main granulocyte present in bronchial brush biopsy specimens and correlated with airway responsiveness to saline solution (r = –0.75), methacholine (r = –0.74), peak flow variability (r = 0.59), and clinical asthma severity (r = 0.57). Eosinophils were the main granulocyte present in sputum and correlated with airway responsiveness to saline solution (r = –0.63) but not with other clinical markers of asthma severity. Bronchoalveolar lavage cell counts were not related to clinical asthma severity. Conclusions: In asthmatic patients treated with cortico-steroids, the dominant inflammatory effector cell in the epithelium is the metachromatic cell, and in sputum it is the eosinophil. These cells correlate with the degree of airway hyperresponsiveness. Clinical asthma severity correlates with airway responsiveness and epithelial metachromatic cells. Induced sputum eosinophils and airway responsiveness to hypertonic saline solution may be useful markers of airway inflammation for clinical practice. (J Allergy Clin Immunol 2000;105:752-9.)

Section snippets

Subjects

Twenty nonsmoking adults (10 women) with a wide range of asthma severity participated in this study (Table I).

. Subject characteristics at baseline

Subject No.Age (y)Allergy*Asthma duration (y)Inhaled steroid (μg/d)FEV1 (% predicted)PD20 (μmol)
  1672112000†970.10
  24911101500†890.08
  3514302000†932.31
  459032000810.33
  5373112000840.51
  644915400740.18
  741411‡2000†840.02
  831321‡0†980.05
  939881000730.50
 1029513‡400†790.08
 1136620‡400†880.12
 1233014‡250†890.49
 133431100010613.70
 143748‡2000†932.94
 1550042000813.27
 16656

RESULTS

At the completion of high-dose inhaled corticosteroid therapy, clinical asthma scores were rated as severe in 9 subjects, moderate in 6 subjects, and mild in 4 subjects (Table II).Many (60%) of the subjects had persisting methacholine airway hyperresponsiveness, with an absent plateau response (80%) and increased variability of peak expiratory flow (Table II). Most subjects (12, 60%) also had persisting hyperresponsiveness to the indirect-acting stimulus hypertonic saline solution. Clinical

DISCUSSION

This study evaluates the relationship among airway inflammation, airway hyperresponsiveness, and clinical asthma severity in corticosteroid-treated asthma. We assessed airway inflammation in 2 distinct compartments, the epithelium and the lumen, in subjects treated with a standardized optimal course of treatment with an inhaled corticosteroid. We then assessed the clinical severity of asthma by a composite score as recommended in current management guidelines. Our results indicate that in

Acknowledgements

We thank Gaye Sheather for administrative assistance and Joy Hopkins for technical assistance.

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    Supported by the National Health and Medical Research Council of Australia and the Asthma Foundation of New South Wales.

    ☆☆

    Reprint requests: Peter G. Gibson, MBBS, FRACP, Airways Research Centre, Department of Respiratory Medicine, John Hunter Hospital, Locked Bag 1, Hunter Mail Centre Newcastle, NSW, Australia 2310.

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