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Keywords:

  • allergen;
  • asthma;
  • methacholine;
  • remodelling;
  • resistin-like molecule-β

ABSTRACT

Background and objective:  Resistin-like molecule-β (RELM-β) is a necessary and sufficient stimulus for airway remodelling in animal models of asthma, but until recently, its role in human disease had not been investigated. The hypothesis that RELM-β expression would increase with increasing asthma severity and further increase following acute bronchoconstrictor challenges has been examined.

Methods:  Bronchial biopsies from healthy subjects and patients with mild and severe asthma were immunostained for RELM-β, as were airway biopsies obtained in mild asthmatics before and 4 days after repeated inhalation challenges with either allergen, methacholine or methacholine preceded by salbutamol as a control. Bronchial brushings were also evaluated for RELM-β mRNA.

Results:  RELM-β immunoreactivity, which co-localized to airway epithelial cells, increased with disease severity; healthy volunteers, median per cent epithelial area 1.98%, mild asthma 3.49% and severe asthma 5.89% (P < 0.001 between groups). RELM-β immunoreactivity significantly and inversely correlated in asthma with forced expiratory volume in 1 s % predicted (P = 0.005). Acute changes in immunoexpression were evident after repeated inhalation challenge with allergen (2.15 % to 4.35 % (P = 0.01)) and methacholine (4.21 % to 6.16 % (P = 0.01)) but did not change in the salbutamol/methacholine challenge group. These changes correlated with change in basement membrane thickness (r = 0.38, P = 0.02). Epithelial RELM-β gene expression was not altered in asthma.

Conclusions:  RELM-β may play an important role not only in animal models of airway remodelling, but also in human airway pathology.