EFFECT OF TONICITY OF NEBULIZED COLISTIN ON CHEST TIGHTNESS AND PULMONARY-FUNCTION IN ADULTS WITH CYSTIC-FIBROSIS

Background - Inhalation of hypertonic nebulised colistin causes chest tightness and is a reason for discontinuing the treatment. This study examines the relationship of chest tightness and change in lung functi on in response to the inhalation of a range of tonicities of nebulised colistin and their influence on patients' preference. Methods - Twent y seven adult patients with cystic fibrosis and a mean forced expirato ry volume in one second (FEV1) of 54% predicted (range 24-98) were stu died. They inhaled a nebulised solution of hypertonic, isotonic, and h ypotonic colistin over three consecutive days in random order in a dou ble blind fashion. Measurements of chest tightness, using a visual ana logue scale (VAS), and FEV1 were recorded before and 0, 15, 30, 60, an d 90 minutes following inhalation. The solution preferred by each pati ent was determined at the end of the three days. Results - All tonicit ies caused a significant fall in FEV1 % predicted and an increase in c hest tightness, with no differences between the solutions. However, th e mean (SE) time to the maximum fall in FEV1 % predicted was significa ntly different between the solutions (hypertonic 7.8 (2.1) min, isoton ic 19.2 (5.5) min, and hypotonic 34.2 (5.9) min) with a mean differenc e (95% CI) between hypotonic and hypertonic solutions of 28.04 (14.6 t o 41.5) min, between isotonic and hypertonic solutions of 12.0 (-0.1 t o 24.1) min, and between hypotonic and isotonic solutions of 15.6 (1.8 to 29.4) min. Positive correlations existed for the maximum fall in F EV1 % predicted between the hypertonic and isotonic solutions (r = 0.6 2, p <0.001) and between the hypotonic and isotonic solutions (r = 0.6 4, p <0.001). There was no correlation between the objective and subje ctive measurements for any solution. The patients) preference varied. Conclusions - All tonicities of colistin caused equal symptoms of ches t tightness and reduction in pulmonary function. It is recommended tha t the patient is challenged with nebulised colistin before prescriptio n of the drug and that the challenge is preceded by an inhaled broncho dilator. Most of the patients preferred the isotonic or hypotonic solu tions. The isotonic solution reflects a fall in FEV1 representative of all the solutions. The fall in FEV1 to the hypotonic solution occurre d over a longer period and may be better tolerated by some patients.