Loss of bronchoprotection to Salbutamol during sputum induction with hypertonic saline: implications for asthma therapy

Background: Sputum induction with hypertonic saline in obstructive airway diseases is generally safe. However, saline induces bronchoconstriction in some patients despite pre-medication with Salbutamol. Our objectives were to investigate the predictors of failure of Salbutamol to protect against saline-induced-bronchoconstriction in patients with asthma and COPD and to evaluate implications for asthma therapy. Methods: Retrospective survey on a database of 3565 patients with obstructive airway diseases who had sputum induced with hypertonic saline. The effect of baseline FEV1, bronchitis and concomitant medication on saline-induced-bronchoconstriction (>= 15% drop in FEV1) were examined by logistic regression analysis. A subgroup had this re-examined 8-12 weeks after decreasing long-acting-beta-2-agonist dose or after adding Montelukast, which included an assessment of mast cell activity in sputum. Results: 222 (6.2%) patients had saline-induced-bronchoconstriction despite pre-treatment with inhaled Salbutamol. Baseline airflow obstruction (FEV1 % predicted < 60% OR 3.29, p < 0.001) and long-acting-beta-agonist use (OR 2.02, p= 0.001), but not bronchitis, were predictors of saline-induced-bronchoconstriction, which decreased when long-acting-beta-agonist dose was decreased. Refractoriness to subsequent bronchodilation was associated with mast cell activity and was attenuated by Montelukast. Conclusion: Sputum induction with saline provides information on bronchitis and additional physiological data on tolerance to beta-agonists and mast cell activity that may have implications for clinical therapy.