A double blind randomised placebo controlled pilot study of oral co-trimoxazole in advanced fibrotic lung disease

Pulm Pharmacol Ther. 2008;21(1):178-87. doi: 10.1016/j.pupt.2007.02.001. Epub 2007 Feb 27.


Background: In 1996, clinical improvement with oral co-trimoxazole was noted in a patient with biopsy proven advanced fibrotic lung disease who was awaiting a lung transplant. Subsequently, 14 patients with end stage fibrotic lung disease also responded to oral co-trimoxazole. This prompted a double blind randomised placebo controlled pilot study in patients with advanced stages of idiopathic interstitial pneumonias (IIP) to objectively measure benefit.

Patients: Twenty patients (aged 49-84 years; 11 males) with progressive fibrotic lung disease who had differing subtype diagnosis from CT scans of progressive fibrotic IIP, and showed oxygen desaturation on exertion were selected.

Method: A detailed assessment of arterial gases, lung function, and progressive shuttle-walking tests combined with oxygen saturation monitoring. Quality of life data was recorded. Randomisation was to co-trimoxazole or identical placebo for 3 months followed by 6 weeks of pulmonary rehabilitation before decoding. Placebo patients received active treatment upon decoding with continued follow up of all patients.

Main outcome measures: Primary 1. Shuttle walking test. Secondary 2. FVC and quality of life.

Results: Active treatment showed a significant improvement in shuttle walking test from 255 to 355 m (p=0.002) (95% CI 200-450) with reduced oxygen desaturations during exercise (p=0.003). FVC improved on treatment (+21%) from median 1.9 to 2.3 L (p=0.05) (95% CI 1.3-3.0) but TLC and DLCO were not significantly changed although stable at 12 months. The MRC 5 Point Dyspnoea Score showed improvement (p=0.05) at 3 months for the active group which was maintained at 12 months. The SGHRQ showed a significant reduction in symptom scores at 12 months (p=0.05). The placebo group showed no significant change in any parameters, but demonstrated identical improvement following oral co-trimoxazole. Serum vascular endothelial growth factor (VEGF) was reduced 50% in the active group at 3 months, but just failed to reach statistical significance. 'Out of study' HRCT scans in 12 patients showed significant reduction in ground glass changes (p=0.05) after 12 months of continuous co-trimoxazole treatment.

Conclusion: The findings of the pilot study show significant improvements in objective and subjective parameters which fulfil the ATS/ERS (2000) criteria of 'a favourable response to treatment'.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Infective Agents / therapeutic use*
  • Blood Cell Count
  • Blood Gas Analysis
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / physiopathology
  • Quality of Life
  • Respiratory Function Tests
  • Tomography, X-Ray Computed
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*
  • Walking


  • Anti-Infective Agents
  • Trimethoprim, Sulfamethoxazole Drug Combination