title: Bronchial hyperresponsiveness to histamine correlates with airway remodelling in adults with asthma.
abstract: BACKGROUND
  Chronic eosinophilic inflammation may promote bronchial hyperresponsiveness (BHR), which involves reversible reduction of airflow and airway remodelling such as a thickening of the reticular basement membrane (RBM) and hypertrophy and hyperplasia of airway smooth muscle (ASM). BHR to histamine (Hist) and acetylcholine (ACh) cannot differentiate airway inflammation and remodelling.
  
  
  OBJECTIVE
  To examine the correlations between eosinophilic inflammation or airway remodelling and BHR to Hist or ACh in adults with severe asthma.
  
  
  METHODS
  We examined eosinophils in the sputum of 50 adult patients with severe asthma before inhaled corticosteroid (ICS) treatment. Airway responses to ACh and Hist were measured on separate days after the first hospital visit and before bronchofiberscopy. Bronchial specimens were obtained by bronchofibrescopy for evaluation of RBM and ASM thickening after systemic corticosteroid treatment.
  
  
  RESULTS
  Eosinophil scores in the sputum before ICS treatment were correlated with BHR to ACh but not to Hist. Asthma duration was inversely correlated with % forced expiratory volume in 1 s, %V(50), %V(25), BHR to Hist, and ASM thickness, but not BHR to ACh or RBM. A multivariate logistic regression model showed that Long duration of asthma affected ASM thickness more than it affected %V(50). ASM thickness was inversely correlated with BHR to Hist but not to ACh.
  
  
  CONCLUSIONS
  In adult patients with severe asthma, BHR to ACh is related to the degree of eosinophilic airway inflammation, whereas BHR to Hist indicates airway remodeling, particularly ASM hypertrophy.
authors.affiliation: National Hospital Organization Sagamihara National Hospital, Sakuradai Sagamihara, Kanagawa, Japan. n-tsurikisawa@sagamihara-hosp.gr.jp
authors.forename: Naomi
authors.initials: N
authors.lastname: Tsurikisawa
authors.forename: Chiyako
authors.initials: C
authors.lastname: Oshikata
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsuburai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sekiya
authors.forename: Hidenori
authors.initials: H
authors.lastname: Tanimoto
authors.forename: Sayaka
authors.initials: S
authors.lastname: Takeichi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mitomi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Akiyama
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D056151:Airway Remodeling / Q000187:drug effects / Q000502:physiology; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000473:pathology* / Q000503:physiopathology; D001999:Bronchoscopy; D004802:Eosinophilia / Q000473:pathology*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology*; D006632:Histamine / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D013183:Sputum / Q000166:cytology / Q000378:metabolism
chemical_list: D006632:Histamine; D000109:Acetylcholine