Diffuse Lung & Transplant Network
Pulmonary Physiology & Rehabilitation Section
Pulmonary arterial hypertension (PH) and more recently interstitial lung disease (ILD) trials use the 6-minute walk test (6MWT) as a primary outcome due to its ability to conveniently capture a patient’s functional capacity and quality of life. However, interpreting the 6MWT in complex and diverse diseases, such as ILD, presents significant challenges.
A recent article (Harari, et al. Eur Respir Rev. 2022 Aug 23;31(165):220087. doi: 10.1183/16000617.0087-2022) advocates for further research to determine the optimal use of the 6MWT as a clinical endpoint in ILD trials. A decline in 6MWT can represent progression of ILD; ILD-related PH; or musculoskeletal, hematologic, or cardiac etiologies related to the underlying cause of ILD.
To enhance sensitivity, the authors endorse the inclusion of additional parameters in the analysis, possibly as a composite outcome. This would involve integrating the oxygen desaturation profile, dyspnea scores, and heart rate recovery with changes in the 6MWT-distance. They propose this composite measure could serve as a primary endpoint when the study intervention’s impact on clinical performance – either improvement or stabilization of ILD or ILD-related PH – is clearly defined. The prognostic significance of these additional parameters in patients with ILD, however, requires further investigation.
Inter-test reliability requires a standardized 6MWT, as previously proposed for this population (Lancaster, et al. Contemporary Clin Trials. 2021;Nov 25,2020). The standardized test protocol that includes continuous pulse oximetry and heart rate measurement, oxygen titration, and end of test guidelines, will reduce variability and boost reproducibility.
In light of recent advancements in the affordability, convenience, and portability of oxygen consumption (VO2) gas analyzers, we believe that incorporating Vo2 measurements into the 6MWT is a needed incremental improvement. This integration will help define the disease process, its impact on patient performance, and clinical prognosis. Future work should focus on understanding how to effectively estimate Vo2 in combination with a standardized 6MWT to make this test a reliable clinical outcome in trials.
Ruchicka Sangani, MD, Section Fellow-in-Training
Saqib Baig, MD, Section Member-at-Large