key: cord-0711414-zh3a5ccw authors: Oliveira, L. V. F.; Oliveira, M. C.; Lino, M. E. M.; Carrijo, M. M.; Afonso, J. P. R.; Moura, R. S.; Galvao, L. S.; Povoa, E. R. P.; Oliveira, L. F. R. J.; Reis, B. M.; Diniz, R. H. C. O.; Bernardes, R. R.; Coutinho, J. C.; Silva, A. S.; Fonseca, D. R. P.; Fonseca, A. L.; Santos, D. B.; Modesto, G. P.; Maldaner, V. Z.; Oliveira-Silva, I.; Martins, R. A. B. L.; Martins, P. S. L. L.; Oliveira, C. S.; Palma, R. K.; Cipriano Junior, G.; Vieira, R. P.; Alves, L. R.; Insalaco, G. title: Outpatient and Home Pulmonary Rehabilitation Program Post COVID-19: A study protocol for clinical trial date: 2022-04-10 journal: nan DOI: 10.1101/2022.04.08.22273608 sha: c7656f3f00ef590330f478e54858817b50b61f4e doc_id: 711414 cord_uid: zh3a5ccw Background The coronavirus disease 2019 (COVID-19) is a widespread, highly contagious inflammatory process that causes respiratory, physical and psychological dysfunction. COVID-19 mainly affects the respiratory system and evolves in the acute phase from mild cases with common symptoms, such as fever, cough, and fatigue, to the moderate-to-severe form, causing massive alveolar damage resulting in dyspnea and hypoxemia that can rapidly progress to pneumonia, and acute respiratory distress syndrome. The acute form usually causes severe pulmonary sequelae such as pulmonary fibrosis or progression to organ failure, leading to worsening metabolic dysfunction and/or death. Purpose To verify the effects of an outpatient and home pulmonary rehabilitation program (PRP) on clinical symptoms, pulmonary function, physical activity level, functional status, autonomic activity, peripheral muscle strength, static and functional balance, functional mobility, anxiety and depression, post-traumatic stress, quality of life, and survival of patients with sequelae from COVID-19. Methods This study will be a cohort, parallel, two-arm multicentric study, to be carried out in three clinical centers, with blind evaluation, with 06 weeks of training and follow-up. This study was designed according to the recommendations of the CONSORT statement. To be involved in this clinical study, according to the inclusion criteria, women and men aged between 16 and 75 years affected by COVID-19. The proposed PRP is based on the guidelines recommended by the Global Initiative for Chronic Obstructive Lung Disease and, consists of a combination of aerobic and muscle strengthening exercises, lasting six weeks, with a frequency of three times a week. Discussion In patients infected with COVID-19 with persistent symptoms and sequelae, PRP mainly seeks to improve dyspnea, relieve anxiety and depression, prevent, and reduce complications and/or dysfunctions, reduce morbidity and mortality, and improve health-related quality of life. Trial registration: This study was registered at clinicaltrials.gov (ID: COVID-19 PULMONARY REHAB NCT04982042). The most common complaints reported in scientific literature after 140 COVID-19 are caused by physiological, immunological, and inflammatory 141 changes in response to infection, either directly by the virus or indirectly by the 142 patient's immune response [14, 15] . The main complaints were dyspnea and 143 persistent fatigue followed by acquired muscle weakness, pulmonary 144 dysfunction, intolerance to moderate efforts, myalgia and arthralgia, post-145 traumatic stress disorder (PTSD), anxiety, and depression, which justify the 146 worsening of functional status and quality of life in these patients [11, 12, 16, 17] . 147 The fact that the frequency and severity of post-disease symptoms are not 148 directly associated or are exclusive to patients in the risk group or who develop 149 the severe form makes it an urgent need to characterize risk predictors and the 150 potential differences between post-intensive care syndrome and the assignment 151 of rehabilitation programs to minimize sequelae [18, 19] . 152 The scientific community and health professionals have discussed the 153 challenge of rehabilitating these patients who present with an infinity of clinical 154 manifestations, considering that knowledge is an important variable in 155 formulating guidelines aimed at structuring the organization, clinical treatment, 156 and pulmonary rehabilitation of these patients with a focus on the Pulmonary rehabilitation is defined as "a multidisciplinary intervention 164 based on personalized assessment and treatment, which includes exercise 165 training, education, and behavioral modification designed to improve the 166 physical and psychological condition of people with respiratory disease" [25] . In Study design 189 This study will be a cohort, parallel, two-arm multicentric study, to be carried out CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 Many patients who seek care in the city come from neighboring cities and 211 therefore do not have an assistance service in the field of pulmonary 212 rehabilitation, and international biosafety standards for protection against 213 COVID-19 will be observed. 24, 2020, under protocol number 4,235,203. 220 This clinical trial was registered at ClinicalTrials.gov (ID: COVID-19 221 PULMONARY REHAB NCT04982042). Involvement in the study will be 222 voluntary, and leave will be allowed at any time without any burden. Participants 223 will be required to sign an informed consent form after receiving all information 224 about the pulmonary rehabilitation program. Participants: recruitment and eligibility criteria 226 To be involved in this clinical study, according to the inclusion criteria, women 227 and men aged between 16 and 75 years affected by COVID-19 will be invited. The following are the inclusion criteria: Age 16-75 years 231 Patients who have been affected by COVID-19 and with impaired lung function 232 . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 10, 2022. Program consists of a combination of aerobic and muscle strengthening 277 . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. professional on the research team and will be encouraged to follow the protocol 296 at home. The aerobic conditioning of this group will be performed by walking on 297 a flat terrain for up to 20 min, with an intensity of 60% to 80% of the maximum 298 heart rate reached in the 6 MWT, respecting individual tolerance and self-299 monitoring throughout the training. You will be asked to complete a diary for 300 each training session. During the 6 weeks of training, individuals will receive 301 weekly phone calls from the same researcher on the team to monitor the load 302 increase, detect any type of problem, clarify possible doubts, and reinforce the 303 importance of rehabilitation. Patients will be recommended to decrease the 304 intensity or discontinue the exercise in case of a high degree of dyspnea or any 305 other symptom of discomfort. The criteria for load increment in the upper-and 306 lower-limb exercises will be the same as those for the outpatient group. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint Upon completing 6 weeks of activities in the pulmonary rehabilitation program, 308 patients will be recruited for a new evaluation, discharged, and encouraged to 309 continue physical activities inherent to PRP at home. Each month, a new 310 telephone contact will be made by a blinded evaluator asking about the general 311 health status, adverse effects, and guidance regarding the continuity of physical 312 activities. Outcomes and measurements 314 All data regarding the initial and final evaluations after 6 weeks of training will be 315 collected by two physiotherapist researchers from the team. The collected data 316 will be registered in standard forms for each outcome and then entered into an 317 Excel database for further analysis. Pulmonary function tests will be performed 318 by a technician trained in pulmonary function and interpreted by a 319 pulmonologist. Physical therapists will perform muscle strength and exercise 320 capacity tests. Quality of life questionnaires and anxiety, depression, and stress 321 scales will be administered by an expert psychologist. All physical activities in 322 the PRP will be monitored by two physiotherapists, who will continuously check 323 the patients' vital signs. Below, we present the outcomes that will be evaluated 324 in the baseline evaluation and after 6 weeks of participation in the program. The 325 outcomes, measures, and assessment methods adopted in this clinical trial are 326 shown in Table 2. 327 Table 2 . Outcomes, measures, and assessment methods that will be used in 328 this clinical trial. Pulmonary Function (FVC, VEF1, Spirometry test X X . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. Anxiety Scale and the Self-Assessment of Depression Scale; IES-6: Event 337 Impact Scale -6. 338 339 . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint were chosen for all analyses, regardless of the best curve. The ATS/ERS 348 acceptability criteria for spirometry will be applied, including a minimum of three 349 respiratory maneuvers with at least two being free from artifacts. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint 364 Due to the wide variety of clinical symptoms and sequelae presented by 365 patients after COVID-19, it is of great importance to have a simple and 366 reproducible tool to assess the impact of the disease, monitor its evolution, and 367 guide rehabilitation actions [53, 54] . Given the high incidence of pulmonary CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint In patients with chronic obstructive pulmonary disease (COPD), it has been 389 observed that the interaction between dyspnea, physical deconditioning, and . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10. 1101 /2022 This is an open-access tool that collects data on physical and 436 psychosocial health, occupational status, and socioeconomic variables, as well 437 as pre-COVID-19 baseline data that make it possible to characterize the 438 physical and psychosocial repercussions after hospital discharge and/or sharp. Kuopio, Finland). This software is widely known and is used worldwide with 459 . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint different patient populations and healthy individuals. It is a well-developed, 460 validated, and easy-to-use software for analyzing the behavior of sympathetic 461 and parasympathetic autonomic activities. This software is considered to be the 462 gold standard for HRV analysis. In this clinical research protocol, HRV analysis 463 will be performed during the 6 MWT. Data will be collected using the Kubios CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint patient. After instruction, the participant pressed the dynamometer until . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint The TUG test is an instrument that allows the assessment of functional mobility 510 in different populations as a function of time [84, 85] . To perform the test, the 511 patient had to get up from a standardized chair, walk 3 m at a comfortable pace, 512 return to the chair, and sit down. The test will be performed with the subjects on is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint 556 The FSS is one of the most widely used fatigue self-assessment scales 557 worldwide. This scale classifies the severity of a patient's fatigue symptoms in 558 terms of how they compromise their motivation, physical activity, and ADLs. The 559 scale is composed of a self-report questionnaire with nine items, with scores 560 ranging from 1 to 7, where 1 indicates strongly disagree and 7 indicates strongly CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint EuroQol five dimension five levels (EQ-5D-5L) 579 The EQ-5D-5L version was introduced by the EuroQol Group in 2009 with the 580 aim of improving the instrument's reliability and sensitivity compared to the EQ-581 5D-3L. The EQ-5D-5L consists of the EQ-5D descriptive system, covering five 582 dimensions: mobility, self-care, usual activities, pain/discomfort, and 583 anxiety/depression. Each dimension has five levels of severity: none, mild, 584 moderate, severe, and extreme. The patients will be asked to indicate their . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint The Self-Assessment of Anxiety Scale (SAS) and the Self-Assessment of 604 Depression Scale (SDS) 605 The SAS and SDS are instruments commonly used in the assessment of 606 negative emotions in clinical practice and are frequently applied to assess the 607 state of adults with symptoms of anxiety and depression [102] . Each scale is composed of 20 items, using a four-level score formulated as CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 for PTSD, without confirmation of a clinical diagnosis [106] . The IES-6 is a Sample size and power calculation 652 The sample size was calculated according to Shahin et al. (2008) . This 653 calculation is based on the mean difference in the distance covered in the test, 654 which should be clinically significant. Considering a difference within +8 655 (control) and +46 (intervention), for a sample size of 35 and 36 patients, 656 respectively, and an SD within each group of 9.2, an α error probability of 0, 05, CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 association between the groups and exacerbations/hospitalizations. All CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint encourage and not drop out of the program. Psychological strategies to improve 700 self-esteem will also be adopted by all patients and their caregivers. Potential impact and significance of the study 715 According to the international scientific literature, which shows excellent results 716 of pulmonary rehabilitation for patients with pulmonary diseases, we expect 717 that, with the participation of patients affected by COVID-19 in outpatient and 718 home pulmonary rehabilitation programs, we will obtain benefits in the short, 719 medium, and long term. The potential clinical impact of this study will be to 720 reduce fatigue and dyspnea, increase functional and exercise capacity, reduce 721 limitations in ADLs, improve quality of life, and consequently reduce morbidity 722 and mortality in patients affected by COVID-19. A reduction in decompensation 723 . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint and hospitalizations is also expected, representing a reduction in health costs 724 by the government. It is hoped that with the results of this clinical trial, we can 725 encourage the scientific community to increase the availability of pulmonary 726 rehabilitation programs for the large number of patients surviving 727 improve the quality of life, and increase survival. The results of this clinical trial will be shared with potential users and peers in 742 the field of research, scientific societies, and people formulating public health 743 policies, thus contributing to the progress of science in general and improving 744 the population's quality of life. The results of this study will be presented at 745 scientific conferences and submitted as a manuscript to scientific journals. The 746 database is made available upon request. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint How amendments to the study, including termination, will be dealt with 748 Any changes in the execution of the proposed initial protocol and/or adverse 749 events that occur to patients will be communicated to the Research Ethics 750 Committee of the institution, ClinicalTrials.gov, and the health authorities of our is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 10, 2022. . 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The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 10, 2022. ; https://doi.org/10.1101/2022.04.08.22273608 doi: medRxiv preprint