Effectiveness of a respiratory rehabilitation program including an inspiration training device versus traditional respiratory rehabilitation: a randomized controlled trial

Introduction

SARS-CoV-2 is a virus classified within the Betacoronavirus genus and belongs to the Coronaviridae family, which is the cause of the development of the acute respiratory syndrome known as COVID-19. Among the most common symptoms, there are fever, dry cough, expectoration, dyspnea, anosmia, ageusia, dysgeusia, sore throat, headache, myalgia, arthralgia, nausea, and vomiting (Adil et al., 2021).

Moreover, cardiac manifestations have been described, which can be direct or indirect sequelae due to inflammatory and/or thrombocytopenia (Zheng et al., 2020). These include myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome, pericardial effusion, and cardiac tamponade. These manifestations are more common in subjects with previous cardiovascular disease, worsening the prognosis (Kaye et al., 2021). Thus, musculoskeletal manifestations can be attributed to the direct effect of SARS-CoV-2 on muscle and nerve cells or systemic disturbances triggered by the infection. Prolonged hospitalization can lead to deterioration of the muscular system associated with muscle atrophy and evolution towards sarcopenia, leading to the appearance of fatigue and decreased resistance to exercise (Ramani et al., 2021). Regarding respiratory manifestations, they can be classified as mild, moderate or severe. Mild cases may involve upper respiratory tract infection, sore throat, and cough, which can progress to moderate or severe cases (Elrobaa & New, 2021). Moderate cases may include pneumonia and fever; COVID-19 pneumonia has been described in some cases as either silent pneumonia with fever or silent pneumonia (Teo, 2020). The severe manifestation of COVID-19 include Acute Respiratory Distress Syndrome, and several factors determine the severity of pulmonary manifestations, including viral load, genetic and ethnic factors, comorbidities, age, and sex (Zhang et al., 2020). Neurological (Camargo-Martínez et al., 2021), psychoemotional (Malik et al., 2022) and endocrinological (Clarke, Abbara & Dhillo, 2022) manifestations are also commonly described in SARS-CoV-2 hospitalizations.

Evaluation of the respiratory complications of COVID-19 disease covers a wide range of instrumental and functional tools (Brennan et al., 2022; Kuo & Chen, 2022). Ultrasound imaging (USI) of the diaphragm is unexpensive and portable tool that permits evaluation of diaphragm thickening and movement, both in patients with preserved mobility and those assisted with mechanical ventilation. Data collected from ultrasound imaging of the diaphragm, regarding the muscle’s form, and the changes in dimensions and movement associated with inhalation, is considered reliable (Laghi, Saad & Shaikh, 2021).

In the context of COVID-19, respiratory training plays a crucial role in the management and recovery of subjects. Some authors enhance the importance of exercise respiratory training, such as diaphragmatic breathing, nasal inspiration and active abdominal muscle contraction, with the addition of instrumental respiratory training as interventions to improve respiratory function, alleviating respiratory symptoms in individuals affected by the virus, either in the acute and post-acute rehabilitation, strongly recommending pulmonary rehabilitation due to its positive results in lung function parameters (Wang et al., 2020; Zhao et al., 2022).

Exercise respiratory training focuses on strengthening the respiratory muscles and improving lung capacity. It involves specific breathing exercises such as deep breathing, diaphragmatic breathing and pursed-lip breathing. These exercises aim to improve ventilatory functioning, respiratory muscles strength and quality of life (Vallier et al., 2023).

Instrumental respiratory training involves the use of specialized devices or tools to assist and optimize respiratory function. These tools, such as incentive spirometers, positive expiratory pressure devices or inspiratory muscle training devices, provide targeted respiratory exercises and facilitate lung expansion. They can help improve lung volumes, strengthen respiratory muscles, and enhance airway clearance. Some studies have explored the effect of this training in various pathologies, such as multiple sclerosis (Rietberg et al., 2017), chronic obstructive pulmonary disease (COPD) (Battaglia, Fulgenzi & Ferrero, 2009) or spinal cord injury (Roth et al., 2010).

Both exercise respiratory training and instrumental respiratory training have shown promising results in improving respiratory outcomes in COVID-19 patients. The aim of this study is to verify the effectiveness of a respiratory physiotherapy treatment protocol based in instrumental respiratory training and aerobic exercise vs a traditional respiratory exercise protocol combined also with aerobic exercise, in subjects who have recovered from COVID-19. As a secondary goal, differences in the efficacy of intervention in women and men would be analyzed.

Materials and Methods

Outcome measures

Spirometry: The main variables studied and the process of conducting the test are as follows: forced vital capacity (FVC), which is the maximum volume of air exhaled with maximal effort after a maximal inhalation, represented in liters; forced expiratory volume in one second (FEV1), which is the maximum volume of air exhaled in the first second of the forced vital capacity, represented in liters; the ratio of FEV1 to FVC (FEV1/FVC), represented as a percentage; peak expiratory flow (PEF), which is the maximum instantaneous flow during the forced vital capacity maneuver, represented in liters; forced inspiratory vital capacity (FIVC), which is the maximum volume inspired during a forced inspiration maneuver after a maximal exhalation, represented in liters; and maximum inspiratory pressure (MIP), represented in cmH2O, used to assess inspiratory muscle strength (Adil et al., 2021). The lung function of the 200 participants was evaluated using the Datospir Touch Easy spirometer (Silbemed SAU, 08026 Barcelona, Spain).

In relation to dyspnea and aerobic endurance, the subjects were assessed using the modified Borg subjective scale, for dyspnea and lower limb fatigue, ranging from grade 0 indicating rest to grade 10 indicating extreme effort and dyspnea (4) and the 6-min walk test (6MWD). The 6MWD is a submaximal exercise test used to evaluate aerobic capacity and endurance (Matos Casano & Anjum, 2023).

To evaluate diaphragm function, specifically diaphragmatic thickening, diaphragmatic ultrasound measurement was used. The diaphragm thickness was measured with the participants in a supine position, in B-mode using a linear transducer with a frequency of 7–13 Hz. The measurement was taken on the right hemidiaphragm by placing the linear transducer at the intercostal window between the ninth and tenth ribs, approximately 0.5 to 2 cm below the costophrenic angle, at a depth of 1.5 to 3 cm. Measurements were taken at the end momentum of the expiration (DPH^EXP) and inspiration (DPH^INSP) during normal tidal breathing (Fig. 1), where the most superficial and deepest interface of the diaphragm can be differentiated in the intercostal space between the two ribs at the height of the midaxillary line, as well as dynamically during the breathing maneuver (Laghi, Saad & Shaikh, 2021) (Video S1).

Results

Both groups showed no differences in baseline for all the outcome measures (Table 1), except for age. Flow diagram of the study participants is shown in Fig. 2.

Regarding the efficacy of both interventions (Table 2), both groups showed statistically significant improvement (p < 0.05) between different measurements, with Eta² values showing an effect considered as “large” (0.7–1). Nevertheless, when considering the interaction between group per time, the IT group showed statistically significant differences regarding improvement compared to the RE group, except for oxygen Saturation, Cardiac Frequency and Diaphragmatic Thickness. Size effects are low, except for FVC (Eta² = 0.429), FEV1 (Eta² = 0.441) and FIVC (0.406), which show values considered as medium (Fig. 3).

Due to the heterogeneity of the sample in the age variable, Pearson correlation was applied to all outcomes, showing all values below 0.4, which is considered as weak or non-existent correlation (Table 3).

Regarding differences of the effects of the treatment by sex (Table 4), the analysis did not show any statistically significant results in any variable.

Discussion

The purpose of this randomized controlled trial was to explore the effects of a respiratory training program including a specifically designed tool for the inspiratory phase and aerobic exercise, compared to a traditional respiratory training and aerobic exercise, in post-COVID participants. Both groups experimented improvement in cardiorespiratory parameters, with a decrease in Systolic and Diastolic Pressure, Dyspnea and Lower Limbs fatigue (measured with the Modified Borg Scale), and increased Oxygen Saturation, 6MWD, Diaphragmatic thickness, FVC, FEV1, FEV1/FVC, PEFR, FIVC and MIP. Cardiac Frequency is unexplainable higher in the post intervention measurement, pointing to an internal validity error involving the order in which participants were evaluated in the 6MWD test and Cardiac Frequency register, as the participants plausibly presented an augmented frequency after the effort (Matos Casano & Anjum, 2023). The results support the benefits of the use of technical aids for respiratory training, combined with aerobic exercise, showing statistically significant differences in all variables except for Oxygen Saturation, 6MWD and Diaphragmatic Thickness.

The design of the study included block randomization regarding sex. Differences in women immune response, specifically in COVID-19, have been analyzed in recent literature (Jing et al., 2020; Mínguez-Esteban et al., 2022). Some authors point out the lack of focus in specifical sex differences in COVID-19 studies (Brady et al., 2021; Haitao et al., 2020), that may have lead in lack of dose adjustment in vaccination due to this sex mediated variations described in scientific literature (Cook, 2008). Ursin & Klein (2021), reported different outcomes concerning risk of severe complications, development of immune response and adverse reactions to treatment mediated by sex. In the present study, there were no significant differences in the studied variables in women and men’s responses to treatment. Silveyra, Fuentes & Rodriguez Bauza (2021) reported in their study many examples of respiratory conditions affecting men and women differently, pointing out the importance of hormonal processes that cause physiological but also morphological differences affecting lung development and maturation and also exacerbation of some symptoms in pulmonary diseases. Most of the analyzed outcome measures in the present study have a functional nature, such as dyspnea scales or functional lung capacity, which may be less affected by hormonal factors, and could explain the homogeneity of the effects of the intervention in women and men.

The results of the present study, favor the use of an inspiratory device, combined with aerobic exercise, in post COVID patients. Respiratory rehabilitation has shown a definitely positive impact in COVID subjects, both in face to face and in telematic interventions (de la Plaza San Frutos et al., 2023). Liu et al. (2020), Gloeckl et al. (2021) and Hermann et al. (2020) conducted their studies with traditional abdominal-diaphragmatic ventilation in acute patients, with positive results. Some studies, with a similar design to those presented, can be found in scientific literature. Faghy et al highlighted, through a survey-based study with 381 participants affected by COVID-19 symptoms, the necessity of multidisciplinary programs to address the large impact that this condition has in quality of life (Faghy et al., 2022a), due to the complex interaction of physical restraints, such as fatigue with the rest of the components of the biopsychosocial model, including fuctional status (Faghy et al., 2022b). The necessity of non farmacological approaches, including rehabilitation programs, has been addressed in recent scientific literature, focusing in approaches including exercise programs (Ashton et al., 2022; Faghy et al., 2021). Li et al. (2022) conducted a pulmonary telerehabilitation program during 6 weeks, with respiratory exercises combined with aerobic exercise, compared to a wait-and-see control group, with positive results for 6MWD, that was actively targeted in the aerobic exercise intervention, same as the present study. Nevertheless, there were no significant effects in FEV1, FVC and FEV1/FVC. The differences with our results can be mediated by the fact that their intervention was exclusively online, whereas participants in the present study received more in person individual training (Day 1 and day 15). Although telerehabilitation has multiple advantages (de la Plaza San Frutos et al., 2023), respiratory exercises need to be performed with accuracy to achieve full benefits. Vallier et al., compared in their study an in person vs a home-based rehabilitation program for COVID-19, focusing exclusively on physical exercise and sophrology, but assessing many spirometry parameters, such as FEV1, FVC and FEV1/FVC, finding no differences between groups. These results, combined with the results of Jian’an et al., may add evidence to the fact that pulmonary exercises such as diaphragmatic breathing, may benefit from specific face-to-face training.

Inspiratory muscle training has been also studied in scientific literature for other pathologies such as COPD (Ammous et al., 2023; Langer et al., 2018), older adults (Seixas et al., 2020), heart failure patients (de Azambuja, de Oliveira & Sbruzzi, 2020), etc. IT consists in increasing the workload of the inspiratory muscles by breathing in against a specific external load. In addition, the level of inspiratory endurance achieved during high-endurance IT is approximately two to four times higher than that achieved during aerobic exercise, although the respiratory rate is significantly lower during high-endurance IT compared to aerobic exercise. On the other hand, it should be noted that specific training of the respiratory musculature during IT vs RE according to Hockele et al. (2022) produces a repeated inspiratory resistance by increasing MIP.

A Cochrane Library systematic review by Ammous et al. (2023) showed that isolated strengthening of the respiratory muscles in patients with COPD, did not show differences in functional results. The comparison with the participants in this study must be cautious as COVID-19 sequels may differ from COPD, but the combination of aerobic exercise both in IT and RE groups may be key for this added functional benefits. To the author’s best knowledge, this is the first study combining a specific inspiratory training device with aerobic exercise in COVID-19 patients compared to a control group. Battaglia, Fulgenzi & Ferrero (2009), explored in COPD patients the benefits of a combination of inspiratory and expiratory devices in a 12 month program, showing improvements in MIP, which goes in line with the results of the present study. Xiao et al. (2012) conducted a systematic review of interventions in inspiratory muscle training in stroke patients, finding some heterogeneity in the results, but consistent use of inspiratory training devices.

The results of our study support the generalization of the use of these tools, combined with aerobic exercise, for the improvement of chronic COVID-19 symptoms.

Previous levels of physical activity were not recorded in this study. However, a recent study by Owen et al. (2023) concluded that physical activity previous to infection may not produce any advantage in recovery. General consensus in scientific literature seems to point out to the fact that the impact of COVID-19 in cardiorespiratory system can be reduced including exercise as a part of general healthy living, in a multidisciplinary rehabilitation approach (Arena et al., 2021; Ashton, Philips & Faghy, 2023; Faghy et al., 2023). Nevertheless, patient-tailored rehabilitation and case by case is essential in this yet not fully understood long term sequels of COVID-19 (Ferraro et al., 2021), as there is conflicting evidence about exercise recommendations in chronic fatigue caused by COVID-19 (Wright, Astill & Sivan, 2022).

Regarding diaphragmatic thickness measured by ultrasound imaging (USI), both groups showed improvement, with no statistically significant difference between them. These results are coincident with previous publications reporting increased diaphragm thickness after pulmonary training, measured with USI (Güneş et al., 2022; Vicente-Campos et al., 2021). Recent studies have highlighted the importance of the respiratory muscles status in COVID-19 patients, not only as a predictor for the severity of the infection symptoms, but also as a target for interventions (Severin et al., 2022). Several studies explore diaphragmatic thickness in COVID-19 patients, finding that the decrease in thickness is closely related to disease-mediated changes and prognosis, generally with computed tomography (Parlak, Beşler & Gökhan, 2022; You et al., 2022). USI assessment has the main advantage of accessibility, allowing clinicians to monitor structural changes and relate them to functional changes in a rather unexpensive and safe procedure (Ureyen Ozdemir et al., 2023). As previously discussed, the relationship between respiratory muscular strength and functional outcomes is still unclear. Further studies monitoring both, structural evaluation by USI combined with functional assessment, will help to clarify and reach a better comprehension about this topic.

Conclusions

The results of this study support the hypothesis that respiratory training seems to benefit women and men equally, despite the sex-mediated differences in COVID-19 symptoms. Regarding the addition of instrumental inspiratory training devices to aerobic exercise to promote structural and functional benefits in subjects with COVID-19 respiratory sequels, the results of this study must be taken with caution, as both groups were different in age. USI monitoring of diaphragm thickness along pulmonary rehabilitation programs could expand the knowledge about the links between respiratory function and respiratory muscle’s structure.

Limitations

Some limitations must be acknowledged. Although no substantial correlations were found between age and any of the outcome measures, groups were different in age at baseline, as the authors put the focus in women and men being equally represented in both groups. Moreover, cardiac frequency was higher in the groups in the post assessment but not in the middle term, due to a change in the order of the evaluations that provoked a bias. Patients were measured just after physical exercise (6MWT), which plausibly increased their cardiac frequency. Participants in this study were eligible for recruitment 5 months after COVID-19 diagnosis. Severity of the symptoms during infection was not recorded for this study.

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