Heterogeneous Treatment Effects after Inspiratory Muscle Training during Recovery from Postacute COVID-19 Syndrome

Purpose The objective of this study is to investigate whether heterogeneous treatment effects occur for changes in inspiratory muscle strength, perceived dyspnea, and health-related quality of life after 8 wk of unsupervised home-based inspiratory muscle training (IMT) in adults with postacute coronavirus disease 2019 (COVID-19) syndrome. Methods In total, 147 adults with self-reported prior COVID-19 either completed an 8-wk home-based IMT intervention (n = 111, 92 females, 48 ± 11 yr, 9.3 ± 3.6 months postacute COVID-19 infection) or acted as "usual care"wait list controls (n = 36, 34 females, 49 ± 12 yr, 9.4 ± 3.2 months postacute COVID-19 infection). Results Applying a Bayesian framework, we found clear evidence of heterogeneity of treatment response for inspiratory muscle strength: the estimated difference between standard deviations (SD) of the IMT and control groups was 22.8 cm H2O (75% credible interval (CrI), 4.7-37.7) for changes in maximal inspiratory pressure (MIP) and 86.8 pressure time units (75% CrI, 55.7-116.7) for sustained MIP (SMIP). Conversely, there were minimal differences in the SD between the IMT and the control group for changes in perceived dyspnea and health-related quality of life, providing no evidence of heterogeneous treatment effects. Higher cumulative power during the IMT intervention was related to changes in MIP (β = 10.9 cm H2O (95% CrI, 5.3-16.8) per 1 SD) and SMIP (β = 63.7 (32.2-95.3) pressure time units per 1 SD), clearly indicating an IMT dose response for changes in inspiratory muscle strength. Older age (>50 yr), a longer time postacute COVID-19 (>3 months), and greater severity of dyspnea at baseline were also associated with smaller improvements in inspiratory muscle strength. Conclusions Heterogeneous individual responses occurred after an 8-wk home-based IMT program in people with postacute COVID-19 syndrome. Consistent with standard exercise theory, larger improvements in inspiratory muscle strength are strongly related to a greater cumulative dose of IMT.