Failure of cromolyn sodium to reduce the incidence of bronchopulmonary dysplasia: a pilot study. The Neonatal Cromolyn Study Group. A controlled study of education for improving compliance with cromolyn sodium (Intal): the importance of physician-patient communication.
This prospective, randomized, blinded clinical trial was conducted to test whether therapy with cromolyn sodium might decrease the incidence or severity of bronchopulmonary dysplasia when given to newborns with respiratory distress syndrome. Cromolyn (20 mg) or placebo was aerosolized to intubated newborns with respiratory distress syndrome every 6 hours, beginning on the first day of intubation. Patients were stratified by birth weight less than 1000 g and 1000 to 2000 g; primary outcome success was defined as survival to 30 days without oxygen dependence. Of 10 patients enrolled who were less than 1000 g birth weight, there were no treatment successes, preventing outcome analysis. The study was discontinued after 28 patients of 1000 to 2000 g birth weight had been studied, at which time it had been found with 95% confidence, with a power of .80, that cromolyn sodium did not decrease by 50% the incidence of bronchopulmonary dysplasia. Severity of bronchopulmonary dysplasia was also similar, with 4 patients in the treatment group and 3 in the placebo group receiving mechanical ventilation at 30 days. Possible reasons for this study outcome include (1) a delivered dose too small to produce a clinical effect; (2) the start of therapy too late to prevent the onset of inflammation; (3) inadequate effect of cromolyn on polymorphonuclear cells in vivo; or (4) development of bronchopulmonary dysplasia through factors unaffected by the actions of cromolyn. The effectiveness of an educational program to increase compliance with cromolyn sodium was assessed in 31 children and adolescents 6 to 17 years of age. Patients were randomly assigned to an education or noneducation group. A standard education program regarding asthma and asthma medications was provided to the education group during four monthly visits. At each visit, all patients were assessed in terms of knowledge of asthma and medications, asthma-related symptoms, and pulmonary function. Patients were also asked to self-rate their compliance. The education program increased the patients' knowledge of cromolyn, and appeared to result in increased cromolyn compliance. Post-hoc analyses, however, suggested that increased compliance did not correspond to improved medical status unless the quality of management (by physician and parents) of the child's asthma was taken into account. These results suggest that inadequate management of asthma in children may be a more serious problem than patient noncompliance.
There is currently no evidence from randomised trials that cromolyn sodium has a role in the prevention of CLD. Cromolyn sodium cannot be recommended for the prevention of CLD in preterm infants.