Inhaled Tobramycin and Bronchial Hyperactivity in Cystic Fibrosis Maya Ramagopal, MD, and Larry C. Lands, MD, PhD* Summary. The use of inhaled tobramycin for prophylaxis and treatment of respiratory symptoms in cystic fibrosis (CF) is now widespread. There have been concerns that inhaling the intrave- nous (I.V.) formulation of tobramycin causes bronchoconstriction. Previous studies using this formulation have either not specified the nebulizing equipment, or studied older, more severely affected patients. This study investigated the incidence of bronchoconstriction with tobramycin inhalation in children with mild to moderate CF. We studied 26 patients between the ages of 7 and 17 years, with mild to moderate CF (20 female). Prior to being placed on prolonged inhaled tobramycin therapy, they underwent a “tobramycin challenge.” FEV 1 was measured pre and post challenge. For the test, standard I.V. solution (80 mg/2 mL) diluted with 2 mL of normal saline was nebulized, using the Hudson (Temecula, CA) RCI Updraft II nebulizer. The nebulization lasted 2 min. There was a 3-min “quiet period,” following which FEV 1 was measured. A decrease in FEV 1 by at least 10% post-tobramycin inhalation was considered to be a positive test. Results were analyzed using the Pearson Chi-square test. Five of 26 (19%) had a positive reaction to tobramycin. Sixteen of 26 (61.5%) were using salbutamol on a daily basis at the time of testing but not for 48 hr before the challenge, and 16 of 26 (61.5%) had a pre-tobramycin FEV 1 of 80%. Neither an FEV 1 of <80% (P = 0.93) nor regular use of salbutamol (P = 0.34) were associated with a positive tobramycin challenge. This study suggests that, while bronchoconstriction does occur, many patients do not exhibit bronchoconstriction in response to the standard I.V. preparation and, as prior work suggests, this may be reduced further by pretreatment with salbutamol. Pediatr Pulmonol. 2000; 29: 366–370. © 2000 Wiley-Liss, Inc. Key words: cystic fibrosis; tobramycin; bronchoconstriction; airway reactivity; antibiotic aerosol treatment. INTRODUCTION Pseudomonas aeroginosa is the most common bacte- rial pathogen associated with pulmonary exacerbations in cystic fibrosis (CF). 1 Systemic antibiotic therapy is lim- ited by the poor penetration of most intravenously ad- ministered agents into bronchial secretions and the im- pairment of their biological activity by purulent secretions. 2 The aerosolized route is therefore a rational mode of delivering medications to the site of infection. Delivery of aminoglycosides by the aerosolized route to the lower respiratory tract has been advocated as a means of achieving high antibiotic concentrations at the site of infection. 3 Treatment with twice-daily aerosolized gen- tamicin and carbenicillin in a group of older patients with CF resulted in improved lung function and reduced hos- pitalizations. 4 Inhaled tobramycin at a dose of 80 mg T.I.D. appeared to have a significant effect in arresting or delaying pulmonary deterioration in some patients with CF. 5 More recently, there have been reports of a signifi- cant reduction in rates of hospitalization following the use of daily or intermittent aerosolized aminoglyco- sides. 6–8 Despite the obvious advantages of inhaled antibiotics, there have been concerns regarding adverse effects. In- halation of the standard intravenous (I.V.) preparation of tobramycin has been implicated in causing adverse ef- fects such as bronchoconstriction, chest tightness, and cough in some CF patients. 9 While the exact mechanisms causing bronchoconstriction are not clear, several etiol- ogies have been suggested, such as tonicity of the solu- tion, 10 dose of the drug, 9 mode of delivery, 11 presence of additives in the solution, 9 and an inherent increase in bronchial reactivity in CF patients. 12,13 We investigated whether the standard I.V. preparation Department of Respiratory Medicine, Montreal Children’s Hospital, Montreal, Province of Quebec, Canada. Grant sponsor: Fonds de la Recherche en Sante ´ du Que ´bec. *Correspondence to: Dr. Larry C. Lands, Department of Respiratory Medicine, Montreal Children’s Hospital, Room D-380, 2300 Tupper St., Montreal, Quebec H3H 1P3, Canada. E-mail: llanpul@mch.mcgill.ca Received 9 June 1999; Accepted 5 January 2000. Pediatric Pulmonology 29:366–370 (2000) © 2000 Wiley-Liss, Inc.