Oral non-steroidal anti-inflammatory drug therapy for cystic fibrosis

Maintenance of optimal lung function is an important therapeutic goal in cystic fibrosis as it is lung damage that, in the long term, is responsible for most premature death among affected people. It has been hypothesised that lung damage results from inflammation and that prolonged use of non-steroidal anti-inflammatory drugs may prevent progressive pulmonary deterioration and respiratory morbidity in cystic fibrosis. It is thus important to establish the current level of evidence about the potential benefits and harms of treatment with non-steroidal anti-inflammatory drugs.

The aim of this systematic review is to assess the effectiveness of treatment with non-steroidal anti-inflammatory agents in cystic fibrosis.

Trials were ascertained from the Cochrane Cystic Fibrosis and Genetic Disorders Specialised Register of Controlled Trials which includes published and unpublished trials identified through electronic databases such as Medline and Embase as well as those identified from handsearching of journals and conference proceedings. Pharmaceutical companies manufacturing non-steroidal anti-inflammatory drugs were also contacted to identify any trials of non-steroidal anti-inflammatory drugs in cystic fibrosis. Date of the most recent search of the Group's specialised register: November 1999.

All randomised or pseudorandomised controlled trials, published and unpublished, comparing non-steroidal anti-inflammatory drugs, administered orally at any dose for a period of at least two months, to placebo in patients with cystic fibrosis.

The following outcomes were assessed: objective measures of lung function, nutritional status, radiological assessment of pulmonary involvement, use of intravenous antibiotics, hospital admissions, survival, frequency of major and minor adverse effects and compliance with therapy.

Three trials involving 145 patients aged from five to 39 years with a maximum follow up of four years met the inclusion criteria. Methodological quality was deemed good or adequate in two. Two trials, both reporting effectiveness of ibuprofen in subjects with mild lung disease, were from the same centre and included some patients in common, while the third assessed piroxicam in subjects with more severe impairment of respiratory function. Variation in outcomes reported and their summary measures precluded calculation of pooled treatment estimates. Only one trial reported within-subject changes in pulmonary function and the findings of this trial suggested that there was a greater absolute annual decline in percentage predicted forced expiratory volume in one second among controls than among those treated with ibuprofen. In a post-hoc sub-group analysis this effect was confined to children aged five to 13 years. In addition, in this one trial long term use of high dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status. No major adverse effects were reported but the power of the trials to identify clinically important differences in the incidence of adverse effects was low.

While there is preliminary evidence to suggest that non-steroidal anti-inflammatory drugs may prevent pulmonary deterioration in subjects with mild lung disease due to cystic fibrosis, currently their routine use cannot be recommended. Further trials are required to confirm that their use prevents pulmonary deterioration and is associated with improved nutritional status. Such trials should also address the age group of subjects most likely to benefit, the prevalence of important adverse effects and the optimal dosage schedule as well as any reduction in concomitant therapy. Multi-centre trials will add to the validity of findings by enhancing their generalisability. The question of whether anti-inflammatory treatment prevents lung damage in pre-symptomatic