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

METCALFE, R. S., P. A. SWINTON, K. A. MACKINTOSH, R. M. G. BERG, J. SHELLEY, Z. L. SAYNOR, J. HUDSON, J. DUCKERS, K. LEWIS, G. A. DAVIES, and M. A. MCNARRY. Heterogeneous Treatment Effects after Inspiratory Muscle Training during Recovery from Postacute COVID-19 Syndrome. Med. Sci. Sports Exerc., Vol. 55, No. 10, pp. 1761-1769, 2023. 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 (ss = 10.9 cmH2O (95% CrI, 5.3-16.8) per 1 SD) and SMIP (ss = 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.