Inhaled tobramycin and bronchial hyperactivity in cystic fibrosis

Abstract

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 intravenous (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.” FEV1 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 FEV1 was measured. A decrease in FEV1 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 FEV1 of ≤80%. Neither an FEV1 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.

Bronchial reactions to the inhalation of high-dose tobramycin in cystic fibrosis

“…In the previous study [3] as well as in an independent study from Canada [11] salbutamol significantly reduced the bronchial obstruction after the inhalation of low-dose tobramycin. These results were confirmed by the current study with high-dose tobramycin preparations.…”

“…These results were confirmed by the current study with high-dose tobramycin preparations. Since bronchial obstruction was not always realised by the patient [3,11] the authors recommend that lung function tests should be performed at the first nebulisation with high-dose tobramycin. If lung function testing reveals significant bronchial reactions b-agonists should be used in combination with the nebulisation of high-dose tobramycin preparations.…”

Bronchial Hyperreactivity Related to Inhalation Therapy in Cystic Fibrosis Patients

“…Additionally, particles larger than 5µm in diameter cause cough as a result of inertial impaction at the level of the posterior pharynx. As particle size is directly related to adverse effects, the type of nebulizer used can affect the incidence and/or severity of observed airway obstruction [31].…”

“…Since the early 1980s, several trials have studied inhaled antibiotics as a suppressive treatment of chronic Pa infection in CF [10,[31][32][33][34][35]. As no approved formulations for inhalation were available, drugs were composed from intravenous formulations containing preservatives, with doses selected not by preclinical safety or efficacy testing, but based on how parenteral formulations were composed [75].…”

New Step in the Life Quality Improvement of Patients With Mucoviscidosis: Tobramycin for Anapnotherapy

“…Побочные эффекты были описаны у большего процента пациен-тов, получавших долгосрочную прерывистую терапию, по сравнению с плацебо. У некоторых пациентов после ингаляции может возникнуть бронхоспазм, связан он с конкретными свойствами используемой лекарствен-ной формы (например, рН, консерванты, осмолярность); его развитие можно предотвратить одновременным использованием бронходилататора (например, сальбу-тамола) [18,19].…”