Bronchial reactivity to histamine is correlated with airway remodeling in adults with moderate to severe asthma.
ABSTRACT Chronic eosinophilic inflammation may promote airway remodeling, including thickening of the reticular basement membrane (RBM), hypertrophy and hyperplasia of the airway smooth muscles (ASM), and an increase in the production of tenascin. The authors examined the correlation between airway remodeling and bronchial reactivity to histamine (Hist) and acetylcholine (ACh) in patients with moderate to severe asthma.
In 30 adult patients with asthma, the authors assessed bronchial hyperresponsiveness (BHR) to various concentrations of ACh and Hist by measuring decreases in forced expiratory volume in one second (FEV₁) of >20% from the preprovocation state, and % recoveries of FEV₁ after inhalation of β-stimulant. After corticosteroid therapy, the authors evaluated the thickening of RBM and ASM and the production of tenascin in bronchial specimens.
The % decrease in FEV₁ was correlated with the % recovery in FEV₁ after provocation by ACh or Hist. Hypertrophy of ASM was correlated with the % decrease in FEV₁ after provocation by Hist, but not by ACh. Thickening of ASM, up-regulation of tenascin in RBM, and duration of asthma were inversely correlated with the % recovery of FEV₁ after provocation by Hist, but not by ACh.
In adult patients with moderate to severe asthma, a strong bronchial contraction provoked by Hist and a subsequent small recovery indicate airway remodeling.
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ABSTRACT: To determine the site in the parasympathetic pathway responsible for the increased bronchial reactivity in 5 atopic subjects, we studied the effect of premedication with aerosols of hexamethonium, a ganglionic blocking agent, and atropine, a postganglionic blocking agent, on the bronchomotor responses to histamine and methacholine aerosols. After 7 mg of aerosolized atropine, baseline specific airway resistance (SRaw) decreased, and the increases in SRaw produced by histamine and by methacholine were prevented in each subject (p < 0.001). After 1 g of hexamethonium, baseline SRaw was decreased to a similar level, and the increase in SRaw produced by histamine was again Prevented in each subject (P < 0.001); However, the increase in SRaw produced by methacholine was not affected significantly in 3 subjects (p > 0.5) and was increased or decreased only slightly in 2 subjects (p < 0.05). These results suggest that bronchial hyperreactivity in atopic subjects may be due to a change in the characteristics of the efferent parasympathetic pathway at a site distal to the ganglion, possibly at the smooth muscle, and that bronchodilation caused by atropine and hexamethonium cannot, by itself, account for their effects on bronchomotor responses.The American review of respiratory disease 08/1980; 122(1):17-25. · 10.19 Impact Factor
Article: Indirect airway challenges.[show abstract] [hide abstract]
ABSTRACT: Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle. Direct airway challenges have been used widely and are well standardised. They are highly sensitive, but not specific to asthma and can be used to exclude current asthma in a clinic population. Indirect bronchial stimuli, in particular exercise, hyperventilation, hypertonic aerosols, as well as adenosine, may reflect more directly the ongoing airway inflammation and are therefore more specific to identify active asthma. They are increasingly used to evaluate the prevalence of bronchial hyperresponsiveness and to assess specific problems in patients with known asthma, e.g. exercise-induced bronchoconstriction, evaluation before scuba diving. Direct bronchial responsiveness is only slowly and to a modest extent, influenced by repeated administration of inhaled steroids. Indirect challenges may reflect more closely acute changes in airway inflammation and a change in responsiveness to an indirect stimulus may be a clinically relevant marker to assess the clinical course of asthma. Moreover, some of the indirect challenges, e.g. hypertonic saline and mannitol, can be combined with the assessment of inflammatory cells by induction of sputum.European Respiratory Journal 07/2003; 21(6):1050-68. · 6.36 Impact Factor