title: Risk of acute bronchospasm and bronchial hyperreactivity from inhaled acid aerosol in healthy subjects: randomized, double-blind controlled trial.
abstract: OBJECTIVE
  To determine the risk of developing acute bronchial spasm and bronchial hyperreactivity in healthy subjects after inhaling hydrochloric acid aerosol of different pH, since various characteristics of inhaled aerosol, particularly its acidity, contribute to the reduction in lung function in patients with a pre-existing disease.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled trial included 79 healthy volunteers. After submitting a written consent, they were randomized in 4 groups with approximately equal number of participants. Each group was exposed to acid aerosol of different pH. The respiratory lung function expressed by forced expiratory volume (FEV1), forced expiratory flow at 50% (FEF50), 75% (FEF25), and between 25% and 75% of vital capacity (FEF25/75), and non-specific bronchial reactivity were measured after inhalation of hydrochloric acid aerosol of pH 7.0, pH 5.0, pH 3.0, and pH 2.0 and compared with baseline values. Twelve subjects, who reached the threshold doses in both bronchial challenges, were tested again after receiving a systemic beta-blockade with a single oral dose of propranolol.
  
  
  RESULTS
  Significant bronchospasm developed after the inhalation of hydrochloric acid aerosol of pH 5.0, 3.0, and 2.0. After the inhalation of aerosols of pH 5.0 and pH 2.0, all parameters of respiratory lung function (FEV1, FEF50, FEF25, and FEF25/75) significantly decreased. After the inhalation of aerosol of pH 3.0, all parameters significantly decreased except for FEF25, which showed no significant difference (1.84+/-0.46 before vs 1.58+/-0.49 after inhalation; p=0.07). The inhalation of hydrochloric acid aerosol had no significant effect on the level of non-specific bronchial reactivity irrespective of its pH. Eight out of 12 subjects tested again after pretreatment with propranolol and with no significant change in the heart rate showed no change in non-specific bronchial reactivity in comparison with the 4 subjects who reacted with a significant decrease in the heart rate (>10%), as well as in non-specific bronchial reactivity (p=0.023).
  
  
  CONCLUSIONS
  Inhalation of acid aerosol in healthy subjects induced a bronchial spasm, but had no effect on non-specific bronchial reactivity except in subjects under systemic adrenergic inhibition.
authors.affiliation: Department for Occupational and Environmental Health, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, P.O.Box 291, 10001 Zagreb, Croatia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Mirić
authors.forename: Davor
authors.initials: D
authors.lastname: Plavec
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000336:Aerosols; D000704:Analysis of Variance; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D016084:Bronchoconstriction / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006851:Hydrochloric Acid / Q000009:adverse effects / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D012129:Respiratory Function Tests
chemical_list: D000319:Adrenergic beta-Antagonists; D000336:Aerosols; D011433:Propranolol; D006851:Hydrochloric Acid