This systematic review aimed to present the evidence for the use of interventions to improve dyspnoea, other symptoms and quality of life (QoL) in patients with progressive idiopathic fibrotic interstitial lung diseases, who suffer a high symptom burden and impaired QoL in the terminal stages of their disease.
For this review, the authors searched 11 electronic databases for relevant articles published between 1966 and December 2010. They considered any single or combined intervention (with the exception of lung transplantation) for the treatment of idiopathic pulmonary fibrosis, non-specific interstitial pneumonia, cryptogenic fibrosing alveolitis or idiopathic interstitial pneumonia.
Due to the paucity of the evidence, all intervention comparisons (prospective and retrospective) including at least 5 adult patients were considered (total of 34 studies); meta-analyses were however only conducted for randomised, placebo-controlled trials (17 studies). The main outcomes considered included effects on dyspnoea, other symptoms, quality of life (QoL), and 6-minute walking distance (6MWD). The outcome measures used to assess dyspnoea and QoL varied between the studies.
The included studies (range of n=6-826 per study; total n=3635) evaluated a total of 17 drug and 2 non-drug interventions. The following were considered by the authors to have either moderate (supported by single RCTs) or strong (supported by meta-analysis) evidence:
• Pulmonary rehabilitation: Meta-analysis showed an overall significant benefit on 6MWD (effect size 27.4; 95% CI 4.1 to 50.7, p=0.021), with moderate evidence of improvements in QoL (various measures) and mixed results for dyspnoea.
• Pirfenidone: Pooled analysis of two RCTs found a significant improvement in 6MWD (absolute difference of 24.0 m; 95% CI 4.3 to 43.7). No significant change in dyspnoea score was seen and there were no QoL data.
• Sildenafil: There was moderate evidence for an improvement in QoL; however an overall benefit on dyspnoea or 6MWD was not supported by meta-analysis. The authors believe that there is insufficient evidence to support the use of sildenafil in improving dyspnoea, despite recommendations made in a recent review that this be considered.
The authors note that the minimum clinically important difference in 6MWD in patients with idiopathic pulmonary fibrosis has been reported as 24-45m; the pooled data for both pulmonary rehabilitation and pirfenidone were within this range.
Weak evidence (supported by non-RCT study designs) was located for oxygen, prednisolone, diamorphine, D-pencillamine, colchicine, interferon α, thalidomide and doxycycline; further investigation of these treatments is required. Although interferon γ-1b (IFNγ-1b) was the most tested intervention, there were no significant effects on 6MWD, dyspnoea, or cough.
The authors discuss the limitations of the data, including the paucity of RCTs, the lack of powering for symptoms or QoL, poor reporting of data, poor use of validated outcome measures, and the heterogeneity of measures used. They recommend international consensus regarding patient-reported outcome measures and study methodology to ensure that future trials capture accurate symptom control and QoL data. In addition, they say that careful consideration should be given to how these measures are used and the presentation of data in radical versus palliative treatment contexts (where goals of treatment differ).