Summary of studies included and results (presented as radical or palliative treatments and in order of weighted evidence)
| Intervention | Papers | Patients analysed | Disease group with diagnostic criteria | Type of trial with Jadad score if applicable | Control | Summary of results |
|---|---|---|---|---|---|---|
| Radical treatments | ||||||
| IFNγ-1b | King et al32 Antoniou et al23 Strieter et al25 | 826 50 32 | IPF: ATS/ERS IPF: ATS/ERS IPF: ATS/ERS | RCT (5) RCT (3) RCT (3) | Placebo two-arm colchicine and IFN placebo | No significant effects of IFNγ-1b on 6MWD, dyspnoea and cough. Significant difference in SGRQ symptom domain in one study. No other improvement in QoL seen |
| Sildenafil | Four studies, three papers and three cohorts of patients; Zisman et al6 Jackson et al21 Collard et al20 | 180 161 cont 26 11 | IPF: ATS/ERS IPF: ATS/ERS IPF: ATS/ERS | RCT (5) Quasi-experimental open-label RCT (5) Quasi-experimental open-label | Placebo two-arm sildenafil Placebo No control | Improvement in smaller open-label uncontrolled study of 6MWD which is not supported by RCTs. Less deterioration of dyspnoea in intervention group compared with placebo of one RCT which is not supported by meta-analysis. Some preservation of QoL scores for sildenafil compared with placebo found in RCT |
| Bosentan | King Jr et al (BUILD-1)8 Raghu et al (2nd paper BUILD-1)9 King et al26 | 154 615 | IPF: ATS/ERS IPF: ATS/ERS | RCT (3) RCT (5) | Placebo Placebo | No effects on 6MWD or dyspnoea at rest seen. Minimal QoL changes in all treated population; some more marked benefits in subgroup with biopsies was seen in BUILD-1 but these were not supported by the larger BUILD-3 study |
| Pirfenidone | Noble et al7 (CAPACITY trial 004) Noble et al7 (CAPACITY trial 006) | 348 344 | IPF: ATS/ERS IPF:ATS/ERS | RCT (5) RCT (5) | Placebo Placebo | Positive effect on 6MWD. No significant effect on dyspnoea. No QoL data |
| NAC | Tomioka et al39 Demedts et al31 | 22 155 | IPF: ATS/ERS IPF: ATS/ERS | RCT (3) RCT (4) | Bromohexine Placebo | No evidence for NAC improving 6MWD, dyspnoea or QoL |
| Co-trimoxazole | Varney et al24 | 20 | IIP:ATS/ERS | RCT (5) | Placebo | Some improvements in dyspnoea and SGRQ symptom score but numbers small |
| Etanercept | Raghu et al35 | 87 | IPF: ATS/ERS | RCT (3) | Placebo | No evidence for etanercept improving 6MWD, dyspnoea or QoL |
| Iloprost | Krowka et al18 | 51 | IPF: no criteria given | RCT (3) | Matched placebo | No evidence for iloprost improving 6MWD, dyspnoea or QoL |
| D-pencillamine | Hanania et al34 | 10 | IPF: no criteria given | Quasi-experimental, open-label | No control | Improvement in dyspnoea following administration of D-pencillamine but weak study design and numbers small |
| Interferon α | Lutherer et al37 | 6 | IPF: ATS/ERS | Quasi-experimental, open-label | No control | Improvement in cough following administration of interferon α lozenges but weak study design and numbers small |
| Ribavarin | Agusti29 | 10 | CFA: Turner Warwick | Quasi-experimental, open-label | No control | No improvement in dyspnoea following administration of aerosolised ribavirin |
| Colchicine | Undurraga et al17 | 17 | IPF: Turner Warwick criteria | Quasi-experimental, open-label | No control | Improvement in dyspnoea following administration of colchicine but weak study design and numbers small |
| Doxycycline | Mishra et al40 | 6 | IPF: ATS/ERS | Quasi-experimental, open-label | No control | No improvement in 6MWD following administration of doxycycline. Improvement in QoL but weak study design and numbers very small |
| Prednisolone* | Hope-Gill et al36 Turner-Warwick et al28 Fiorucci et al30 | 6 127 30 | IPF: ATS/ERS CFA: Turner-Warwick IPF: ATS/ERS | Quasi-experimental, open- label Retrospective case note review Quasi-experimental, open-label | No control No control Three arms: colchicine, cyclophosphamide and prednisolone | Some improvement in dyspnoea in prednisolone groups but numbers small and weak study design |
| Palliative treatments | ||||||
| Pulmonary rehabilitation | Holland et al11 Nishiyama et al10 Ozalevli et al12 Rammaert et al13 Kozu et al14 Swigris et al15 | 34 28 15 13 90 14 | IPF: ATS/ERS IPF: ATS/ERS IPF: ATS/ERS IPF:ATS/ERS IPF: ATS/ERS IPF:ATS/ERS | RCT (3) RCT (3) Quasi-experimental, open-label Quasi-experimental, open-label Quasi-experimental, open-label Quasi-experimental, open-label | Telephone advice Usual care No control No control COPD group COPD group | 6MWD improved immediately following pulmonary rehabilitation (however not as much as in COPD). Mixed results for dyspnoea. Positive effects on fatigue and QoL also seen |
| Disease management programme | Lindell et al33 | 21 | IPF: unclear | RCT (2) with qualitative interviews | Usual care | Mixed evidence on benefit of disease management programme in improving symptoms and QoL. Quantitative work suggested negative impact of intervention on perceptions of physical QoL and a tendency for greater anxiety. Qualitative work suggested patients felt less isolated and were able to put their disease into perspective |
| Oxygen | Hicks et al19 Visca et al22 | 70 34 | IPF: ATS/ERS IPF/NSIP: ATS/ERS | Retrospective case note study Retrospective case note study | Two-arm oxygen No control | Improvement in 6MWD and some improvements in dyspnoea in oxygen-treated groups, but weak study designs |
| Diamorphine | Allen et al27 | 11 | IPF: characteristic changes on chest x-ray | Quasi-experimental, open-label | No control | Improvement in dyspnoea following administration of diamorphine. May improve anxiety. Weak study design and numbers small |
| Thalidomide | Horton et al38 | 11 | IPF: ATS/ERS | Quasi-experimental, open-label | No control | Improvement in cough and QoL related to cough following administration of thalidomide but weak study design and numbers small |
*May be considered both a radical and palliative treatment.
ATS, American Thoracic Society; CFA, cryptogenic fibrosing alveolitis; Cont, patients continuing into open label phase; COPD, chronic obstructive pulmonary disease; ERS, European Respiratory Society; IFN, interferon; IPF, idiopathic pulmonary fibrosis; 6MWD, 6-minute walking distance; NAC, N-acetylcysteine; NSIP, non-specific interstitial pneumonia; QoL, quality of life; RCT, randomised controlled trial.