title: Bronchial reactivity in healthy individuals undergoing long-term topical treatment with beta-blockers.
abstract: OBJECTIVE
  To assess the impact of long-term treatment with topical timolol on bronchial reactivity in healthy individuals.
  
  
  METHODS
  Twenty-one otherwise healthy individuals with high-pressure primary open-angle glaucoma were enrolled in a randomized controlled clinical trial. Eleven patients underwent 3 years of topical 0.5% timolol treatment followed by a 1-year washout period; 10 patients underwent primary argon laser trabeculoplasty. Functional variables and bronchial reactivity (forced expiratory volume in 1 second and metacholine challenge test results) were assessed in both groups at enrollment and after 3 and 4 years of follow-up.
  
  
  RESULTS
  After 3 years, a measurable response to metacholine challenge was recorded in 6 of 11 otherwise symptom-free individuals treated with 0.5% timolol twice daily. A detectable response to metacholine challenge was still present in half of these individuals (3 of 6) when further washed out for 1 year from the topical beta-blocker. No significant variation in bronchial reactivity was measured in the laser-treated group during 4 years of follow-up.
  
  
  CONCLUSIONS
  Healthy individuals who undergo long-term topical application of a nonselective beta-blocker (0.5% timolol) can develop a subclinical increase in bronchial reactivity. This phenomenon may not be completely reversible on withdrawal of the beta-blocker.
authors.affiliation: Glaucoma Service, Institute of Ophthalmology, and Department of Respiratory Disease, University of Parma, Parma, Italy. s.gandolfi@rsadvnet.it
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Gandolfi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Chetta
authors.forename: Luca
authors.initials: L
authors.lastname: Cimino
authors.forename: Paolo
authors.initials: P
authors.lastname: Mora
authors.forename: Chiara
authors.initials: C
authors.lastname: Sangermani
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Tardini
mesh_terms: D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000503:physiopathology; D016085:Bronchoconstrictor Agents; D005260:Female; D005541:Forced Expiratory Volume; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008134:Long-Term Care; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000009:adverse effects; D013999:Timolol / Q000008:administration & dosage / Q000009:adverse effects*; D014130:Trabeculectomy
chemical_list: D000319:Adrenergic beta-Antagonists; D016085:Bronchoconstrictor Agents; D009883:Ophthalmic Solutions; D016210:Methacholine Chloride; D013999:Timolol