In this retrospective cohort study, we analyzed 46 patients with advanced lung cancer who were hospitalized for medical treatment between April 2015 and March 2019 and who underwent rehabilitation (Fig 1). The participants were assigned either to the exercise therapy group (control) or the IMT load + exercise therapy group (intervention). Patients who underwent whole-body endurance exercise, such as ergometer riding and treadmill running; with no dyspnea at rest and on exertion; in whom the reliability of tests could not be obtained because of coughing; and with brain metastasis were excluded from the analysis.
This study was approved by the Ethics Committee of Shinshu University (approval no. 4334) and was conducted in accordance with the Declaration of Helsinki (latest version). Informed consent was obtained via the opt-out method, such that the participants had the opportunity to refuse participation in this study.
The patients’ age, sex, body mass index, cancer type and stage, performance status, Barthel index, degree of dyspnea at rest and on exertion (Modified Borg Scale [mBS] rating), type of chemotherapy, line of therapy, use of oxygen therapy, spirometry, and maximal inspiratory pressure (MIP) were retrospectively analyzed. The percentage of vital capacity, forced expiratory volume in 1 second, and forced vital capacity were measured using the Autospiro AS-407 spirometer (Minato Medical Science, Osaka, Japan) based on a previous study.19
MBS rating and MIP are indicators of dyspnea. Thus mBS rating and MIP were measured at three periods, namely, baseline, 1 week later, and 2 weeks later. The mBS is a subjective evaluation scale that measures the degree or intensity of dyspnea at rest and on exertion. It ranges from 0 (nothing at all) to 10 (maximal). The mBS scale was adopted as it was deemed suitable for the evaluation of the relative transitions of dyspnea.
MIP was measured as previously described20 using POWERbreathe Medic Plus KH2 (Entry Japan, Tokyo, Japan). Maximum inspiration was determined from the level of residual air volume in the sitting position, and the pressure was maintained for 3 seconds. The measurement was performed three times, and the maximum values were adopted for analysis.20
The exercise therapy did not include whole-body endurance exercise, such as ergometer riding and treadmill running, so as not to reduce the persistence rate as a result of dyspnea. The exercise therapy mainly involved activities of daily living training, including respiratory muscle stretching, upper and lower limb resistance training, basic movements, and walking, under the guidance of physical therapists.
IMT is believed to improve tolerance not only in the early stage of training but also patient satisfaction and adherence by not inducing dyspnea to a considerable extent. The IMT load + exercise therapy group performed IMT as previously described,21,22 up to 30 times twice daily at a load of 30% to 40% of the MIP, with nose clips attached and under the guidance of physical therapists. MIP was then measured using POWERbreathe Medic Plus KH2, and the load was adjusted to the optimal loading every week.
The clinical backgrounds of the exercise therapy group and the IMT load + exercise therapy group were compared using the χ2 test and Student’s t test. Variations of MIP and mBS rating were examined using 2-way repeated-measures analysis of variance (ANOVA) to investigate the effects of IMT. Mauchly’s test of sphericity was used to test the assumption of sphericity; when it yielded statistically significant results, the Greenhouse-Geisser e correction was used to adjust violations of sphericity. In addition, the Bonferroni method was used for multiple comparisons. Statistical analysis was performed using EZR.23 Descriptive data were expressed as mean ± standard deviation or standard error values. The significance level was set at 5%.