title: Airway reactivity is a determinant of bronchodilator responsiveness after methacholine-induced bronchoconstriction.
abstract: Airway hyperresponsiveness (AHR) is one of the characteristics of asthma and a risk factor for persistent airflow limitation. Poor response to bronchodilator may be a cause of persistent airflow limitation. Multiple factors may determine bronchodilator responsiveness, including airway reactivity to nonspecific bronchoconstrictive agents. If patients with AHR have poor bronchodilator responsiveness, then it could be a potential mechanism for asthma and persistent airflow limitation in these patients. The objective of this study is to assess the relationship between airway reactivity to methacholine and responsiveness to beta-agonist and beta-agonist/anticholinergic combination in a large subject population. A retrospective data analysis was undertaken of 764 consecutive subjects with > or = 20% reduction in forced expiratory volume during the first second of exhalation from total lung capacity (FEV1) after < or = 189 cumulative units of methacholine. The first 382 subjects received 3 inhalations of metaproterenol and the second 382 subjects received 3 inhalations of albuterol and ipratropium combination after > or = 20% reduction in FEV1. Bronchodilator responsiveness was measured as the percent increase in FEV1 after the treatment. Airway reactivity was assessed as the log10 of methacholine dose response slope. In a simple linear regression model, airway reactivity was significantly related to bronchodilator responsiveness. The coefficient of determination (r2) was 0.15 for the whole groups; 0.14 for metaproterenol group and 0.18 for albuterol/ipratropium combination group (all p<0.0001). The regression coefficient (beta) was 14.0 for the whole group; 14.8 and 13.2, respectively, for the two bronchodilator groups. Airway reactivity to methacholine is a determinant of airway responsiveness to both beta-agonist and beta-agonist/anticholinergic combination. Subjects with higher airway reactivity have higher bronchodilator responsiveness.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Memorial Hospital of Rhode Island, Pawtucket, Rhode Island 02860, USA. Annie_Parker@brown.edu
authors.forename: Annie Lin
authors.initials: AL
authors.lastname: Parker
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000175:diagnosis* / Q000188:drug therapy*; D001985:Bronchial Provocation Tests / Q000379:methods; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage; D016014:Linear Models; D008297:Male; D009921:Metaproterenol / Q000008:administration & dosage; D016210:Methacholine Chloride; D008875:Middle Aged; D011336:Probability; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D016210:Methacholine Chloride; D009921:Metaproterenol; D009241:Ipratropium; D000420:Albuterol