title: A double blind randomised placebo controlled pilot study of oral co-trimoxazole in advanced fibrotic lung disease.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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'.
authors.affiliation: Department of Respiratory Medicine, St Helier Hospital, Wrythe Lane, Carshalton, Surrey SM5 1AA, UK. vvarney@epsom-sthelier.nhs.uk <vvarney@epsom-sthelier.nhs.uk>
authors.forename: V A
authors.initials: VA
authors.lastname: Varney
authors.forename: H M
authors.initials: HM
authors.lastname: Parnell
authors.forename: D T
authors.initials: DT
authors.lastname: Salisbury
authors.forename: S
authors.initials: S
authors.lastname: Ratnatheepan
authors.forename: R B
authors.initials: RB
authors.lastname: Tayar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001772:Blood Cell Count; D001784:Blood Gas Analysis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D012129:Respiratory Function Tests; D014057:Tomography, X-Ray Computed; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D016138:Walking
chemical_list: D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination