Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomised controlled trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal condition with limited treatment options. However, in a previous small study, co-trimoxazole was found to be beneficial. METHODS: In a double-blind multicentre study, 181 patients with fibrotic idiopathic interstitial pneumonia (89% diagnosed as definite/probable IPF) were randomised to receive co-trimoxazole 960 mg twice daily or placebo for 12 months in addition to usual care. Measurements were made of forced vital capacity (FVC) (primary endpoint), diffusing capacity of carbon monoxide (Dlco) and EuroQol (EQ5D)-based utility, 6-minute walk test (6MWT) and Medical Research Council (MRC) dyspnoea score (secondary endpoints). All-cause mortality and adverse events were recorded (tertiary endpoints). RESULTS: Co-trimoxazole had no effect on FVC (mean difference 15.5 ml (95% CI -93.6 to 124.6)), Dlco (mean difference -0.12 mmol/min/kPa (95% CI 0.41 to 0.17)), 6MWT or MRC dyspnoea score (intention-to-treat analysis). The findings of the per-protocol analysis were the same except that co-trimoxazole treatment resulted in a significant improvement in EQ5D-based utility (mean difference 0.12 (95% CI 0.01 to 0.22)), a reduction in the percentage of patients requiring an increase in oxygen therapy (OR 0.05 (95% CI 0.00 to 0.61)) and a significant reduction in all-cause mortality (co-trimoxazole 3/53, placebo 14/65, HR 0.21 (95% CI 0.06 to 0.78), p=0.02)) compared with placebo. The use of co-trimoxazole reduced respiratory tract infections but increased the incidence of nausea and rash. CONCLUSIONS: The addition of co-trimoxazole therapy to standard treatment for fibrotic idiopathic interstitial pneumonia had no effect on lung function but resulted in improved quality of life and a reduction in mortality in those adhering to treatment. ISRCTN22201583.

Pleuroparenchymal fibroelastosis: a spectrum of histopathological and imaging phenotypes.

Pleuroparenchymal fibroelastosis (PPFE) is a rare condition characterised by predominantly upper lobe pleural and subjacent parenchymal fibrosis, the latter being intra-alveolar with accompanying elastosis of the alveolar walls. The aim of this study was to review cases fulfilling published imaging and histological criteria, and identify any common clinical features that may suggest an underlying aetiology for a condition that has previously been regarded as idiopathic. Of 12 patients (seven females, median age 57 yrs), the presenting symptoms were shortness of breath (11 out of 12 patients) and dry cough (six out of 12 patients). Seven patients reported recurrent infections during the course of their disease. Five demonstrated nonspecific autoantibody positivity. Two patients had a family history of interstitial lung disease (ILD). High-resolution computed tomography features of lung disease remote from the pleuroparenchymal changes were present in six out of 12 patients (coexistent fibrosis, n=5; bronchiectasis, n=1). Of seven patients with tissue sampled from the lower lobes, four patients showed less intense PPFE changes (one with additional features of hypersensitivity pneumonitis) and three showed usual interstitial pneumonia. PPFE is a distinct clinicopathological entity, with clinical data suggesting a link to recurrent pulmonary infection. Genetic and autoimmune mechanisms may also contribute to the development of these changes. PPFE may also present with more diffuse involvement than previously reported, and coexist with different patterns of ILD.

Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: an economic evaluation alongside a randomised controlled trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fibrotic disease of the lungs of unknown origin with a poor prognosis. A small trial of co-trimoxazole demonstrated improvements in symptoms and functional parameters over a 3-month period. We therefore conducted a larger trial with a concurrent economic evaluation to investigate this antibiotic further. METHODS: We report an economic evaluation alongside a multi-centre, randomised, placebo-controlled, double-blind trial of 12 months therapy with 960 mg co-trimoxazole daily in 181 patients with fibrotic idiopathic interstitial pneumonia (IIP). Patients were recruited from 28 university and district hospitals in the UK and were aged over 40 years with fibrotic IIP. We report costs to the National Health Service (NHS) and society, change in forced vital capacity (primary endpoint) and quality-adjusted life-years (QALYs) gained, incremental cost effectiveness and cost utility ratios over 12 months. RESULTS: From the perspective of society, mean cost per patient in the co-trimoxazole arm was approximately £1177 higher than in the placebo arm, but mean QALYs were 0.053 higher yielding an incremental cost-effectiveness ratio of £22,012 per QALY gained with a 54.44 % probability of being below £30,000. The cost of IPF to UK society in 2011 is tentatively estimated at £124 million, of which 13 % is NHS costs, 1 % social services, 2 % patient out-of-pocket costs and 84 % lost productivity. CONCLUSIONS: Given commonly employed thresholds in the UK NHS, on balance co-trimoxazole may be a cost-effective treatment for IPF, although there is substantial decision uncertainty. However, recent guidance on the use of immunosuppressive therapy in IPF patients should be taken into account prior to any policy decision.