EFFECTS OF INSPIRATORY MUSCLE TRAINING IN POST-COVID-19 PATIENTS
Condition: Covid19
MeSH terms: COVID-19; Respiratory Aspiration
Study type: Interventional

Summary: 
      COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, which had its first case
      identified in December 2019 in Wuhan, China. The disease can cause death and collapse in
      health systems, in addition to increasingly prevalent sequelae. Among the persistent symptoms
      presented by patients in the post-COVID-19 phase, we highlight the respiratory ones. The
      diaphragm - the main muscle of respiration - can also undergo structural and functional
      changes resulting from SARS-CoV-2 infection. This finding is related to some respiratory
      sequelae of the disease, such as severe myopathy of the diaphragm with weakness and decreased
      endurance of the inspiratory muscles, dyspnea, fatigue, and failure in ventilatory weaning.
      Considering that COVID-19 can affect the respiratory muscles of afflicted individuals, it is
      reasonable to assume that inspiratory muscle training should improve inspiratory muscle
      weakness and endurance, and the functional capacity of individuals who had symptomatic
      COVID-19. Objective: To evaluate the effect of inspiratory muscle training on inspiratory
      muscle strength and endurance and on the functional capacity of individuals afflicted by
      COVID-19. Methods: This controlled and randomized clinical trial will be conducted according
      to the guidelines of the Vila Velha University Ethics Committee (CEP-UVV). The sample will
      consist of individuals with a positive diagnosis for SARS-CoV-2 infection assessed by means
      of the reverse transcriptase reaction followed by the polymerase chain reaction (RT-PCR) and
      who have already undergone the period of active infection. These individuals will be invited
      to participate in the study as soon as they are evaluated by the cardiopulmonary
      rehabilitation service. Those who meet all the inclusion criteria, agree to participate, and
      sign the free and informed consent form (FICF), will be randomly assigned to two groups, the
      control group (CG, n = 21) and the treatment group (TG, n = 21). The initial evaluation will
      consist of anamnesis, measurement of indirect blood pressure, heart rate, and peripheral
      oxygen saturation by portable pulse oximeter, analysis of maximum inspiratory pressure (MIP),
      dynamic inspiratory muscle strength index (S-Index), and endurance of the inspiratory muscles
      - which will be collected using a digital training device (PowerBreathe KH2), in addition to
      functional assessment through the 1-minute sit-to-stand test. The reassessment will take
      place six weeks after the start of the program and the same data will be collected at the
      participants' homes. Both groups will undergo the rehabilitation protocol, consisting of
      muscle strengthening and aerobic training, with individual assessment of exercise intensity.
      The treated group will undergo inspiratory muscle training through linear pressure load,
      using the POWERbreathe Classic Medic® device to perform two sets of 30 repetitions daily for
      six weeks. The same physical therapist will oversee the training sessions of all patients.
      Statistical analysis: Data normality will be tested using the Shapiro-Wilk test. To analyze
      the differences between groups, we will use the t-test for parametric data and the Wilcoxon
      test for non-parametric data. The level of significance will be set at 5% (p < 0.05). Data
      will be analyzed using the SPSS 8.0 software and the results expressed as mean ± standard
      deviation or median and interquartile range.
    

Detailed description: 
      This randomized controlled clinical trial will be carried out according to the ethical
      standards for research with human beings and shall be previously approved by the human
      research ethics committee (CEP-UVV); participants will have to sign the free and informed
      consent form (FICF).

      The sample will consist of individuals with a positive diagnosis for SARS-CoV-2 infection
      assessed by means of the reverse transcriptase reaction followed by the polymerase chain
      reaction (RT-PCR) and who have already undergone the period of active infection. The active
      infection period comprises 14 days from the onset of symptoms for those who have not been
      hospitalized and 21 days for those who have been hospitalized. These individuals will be
      invited to participate in the research as soon as they are evaluated by the cardiopulmonary
      rehabilitation service. Those who meet all the inclusion criteria, agree to participate, and
      sign the FICF will be randomly assigned to two groups, the control group (CG) and the
      treatment group (TG). The block randomization scheme will be generated using the
      randomization.com website (http://www.randomization.com). The allocation of participants will
      be carried out by a different researcher from the one who will treat the patients, thus
      ensuring blinding. In addition, the researchers who will collect and analyze the data will be
      different and both blind to the experimental groups and types of intervention.

      Regarding the sample size, as the study was designed to detect a mean difference of 20 cmH2O
      in MIP between groups, with a standard deviation of 15 (Newall; Stockley, 2005), a 95%
      confidence level, and a significance level of 0.05 (two-tailed α), we calculated that each
      group should contain 15 subjects. Considering the possibility of a sample loss of 20-25%, 42
      individuals will be recruited (21 per group). (Newall, 2005).

      The initial assessment will be carried out by the cardiopulmonary rehabilitation service at
      home, in which the following data will be collected: anamnesis; blood pressure (BP)
      measurement by digital sphygmomanometer (Omron® HEM 705CP, Tokyo, Japão); heart rate (HR) and
      peripheral oxygen saturation (SpO2) by the portable pulse oximeter G-Tech Oled Graph®
      (Beijing Choice Electronic Technology Co., Ltd., Beijing, China); MIP, dynamic inspiratory
      muscle strength (S-Index), and inspiratory muscle endurance analyses using the POWERbreathe
      K-series KH2® (POWERbreathe International Ltd., Warwickshire, United Kingdom); and functional
      assessment through the 1-minute sit-to-stand test (1-min STS).

      The reassessment will take place six weeks after the start of the program and the same data
      will be collected at the participants' homes.

      The primary outcome of the study to evaluate inspiratory muscles will be MIP, while S-Index,
      endurance, and functional capacity will be secondary outcomes.

      EVALUATION PROCEDURES:

      1-MINUTE SIT-TO-STAND TEST This test assesses the functional capacity of individuals with
      different types of diseases or dysfunctions. This standardized assessment is performed in an
      armless, 46-cm-high chair. The individual evaluated receives the verbal command to get up and
      sit down from the chair as many times as possible within a 1-minute interval. The main
      outcome of the test is how many times the individual sat and stood up; secondarily, vital and
      perceived exertion data are recorded before, during, and immediately after the test is
      performed.

      MEASUREMENT OF BP, HR, AND SPO2 BP will be measured using a digital sphygmomanometer (Omron®
      HEM 705CP, Tokyo, Japan). The patient will remain seated for five minutes in a comfortable
      chair, with the back relaxed and supported on the backrest, legs uncrossed, left arm
      supported on the table, and free of clothes at arm height. The patient cannot drink alcohol,
      have smoked or exercised 30 minutes before the measurement, and the bladder must be empty.
      Three measurements will be taken with a 2-min interval between them; the first will be
      discarded and the BP value obtained by the average between the last two measurements.

      HR and SpO2 will be measured using the portable pulse oximeter G-Tech Oled Graph® (Beijing
      Choice Electronic Technology Co., Ltd., Beijing, China). Pulse oximetry measures how much
      oxygen the blood is carrying. Through a small device called a pulse oximeter, the blood
      oxygen level can be measured without the need for an arterial blood puncture. To measure
      oxygen, beams of light produced by the device pass through the blood on the finger and are
      "read" to calculate the percentage of oxygen transport. This method also measures HR. The
      accuracy of the oximeter is 2% above or 2% below the saturation that can be obtained by an
      arterial blood gas test. To obtain a better reading, the patient will be instructed to keep
      the hand warm, relaxed, kept below the level of the heart, and not to use fake nails and/or
      nail polish.

      MIP, S-INDEX, AND ENDURANCE ANALYSES To analyze MIP, S-index, and endurance, we will use an
      electronic device employed by health professionals for the assessment and training of the
      inspiratory muscles in patients with dyspnea (POWERbreathe K series KH2®, HaB International,
      Warwickshire, United Kingdom). (POWERbreathe, 2019).

      MIP assessment:

      Initially, the patients will be instructed and familiarized with the device and the maneuver
      that will be performed, in which they will inhale against a closed airway, with prior warming
      of the inspiratory muscles and learning of the technique. MIP will be measured with the
      patients in a seated position. They will be encouraged to slowly exhale all the air and, from
      the residual volume (RV), perform a maximum inspiration. A nose clip and a mouthpiece with a
      bacteriological and viral filter, which must be well attached to the patient's mouth, will be
      used. Three maneuvers with 1-min rest intervals will be performed and recorded. Values must
      vary by less than 20%, and the highest one will be selected.

      The MIP result displayed in the software corresponds to the highest 1-second mean pressure
      achieved during the maneuver (measured at 50 Hz). This measure reflects the pressure
      developed by the respiratory muscles plus the elastic recoil pressure of the respiratory
      system in the residual volume and is an index of global respiratory output rather than a
      direct measure of the contractile properties of the inspiratory muscles. This result will be
      used to monitor the influence of IMT.

      The MIP values predicted for the Brazilian population have been published by several authors,
      and the main equations validated for Brazilians are the ones by: Neder et al.; Costa et al.;
      Simões et al., and Pessoa et al. The present proposal will predict MIP values through the
      equation of Neder et al., in which:

        -  For men: MIP (cmH2O) = 155,3 - (0,80 x age)

        -  For women: MIP (cmH2O) = 110,4 - (0,49 x age)

      S-Index assessment:

      The S-Index is a measure of the dynamic strength of the inspiratory muscles and is derived
      from the result of the peak inspiratory flow registered by the device's sensors in each
      incursion, using a patented algorithm. Unlike the isometric measurement (MIP), in this
      assessment the individual will perform the inspiratory maneuver through a valve with free air
      passage. Inspiratory muscle strength is calculated across the entire range of inspired lung
      volume. The result of the strength index is classified based on the normal values predicted
      for the population studied. These values, which are recorded in cmH2O, are individually
      calculated by the software Breathelink® (POWERbreathe, Warwickshire, United Kingdom), using
      information from the patient's profile. As patient learning has been described regarding this
      parameter, ten maneuvers will be performed in sequence, without rest between attempts, and
      the best result will be considered. The technique for measuring dynamic strength is similar
      to that of MIP, in which the patient must be seated, with a nose clip occluding the air
      passage through the nostrils, and a mouthpiece with a bacteriological and viral filter
      tightly coupled to the mouth.

      Inspiratory muscle endurance assessment:

      The tool POWERbreath K series® (POWERbreathe International Ltd., Warwickshire, United
      Kingdom) enables the performance of endurance tests (Silva et al, 2016). Endurance is the
      ability to sustain a specific task over time. The training load will be predetermined
      manually and introduced gradually over the first five breaths, as this is a constant load
      test, at 60% of the MIP value obtained from each patient. The patient will be instructed to
      breathe as long as possible until no breath can be fully completed, that is, until
      respiratory fatigue occurs. In the absence of respiratory fatigue, the maximum evaluation
      limit will be seven minutes, when the test is successfully completed. The results of
      resistance training will be recorded in the software and include the following parameters:
      Peak Inspiratory Flow (l/s), Training Load (cmH2O), Average Power (Watts), Average Inspired
      Volume (l), and Energy (Joules).

      INTERVENTION CARDIOPULMONARY REHABILITATION All groups will undergo the rehabilitation
      protocol, comprised of muscle strengthening and aerobic training. Muscle strengthening will
      be achieved through a sit and stand up from a chair routine, abduction of upper and lower
      limbs, and rowing; three sets of 10 repetitions of each exercise will be performed. Elastic
      tubes will be used, with elasticity defined by color and indicating the greatest resistance
      the participant can endure with an effort between 4 and 8 on the OMNI-RES scale for perceived
      exertion (Tiggemann et al., 2010; Lagally, Robertson, 2006; Ramos et al., 2014; Ribeiro,
      2021). In addition, aerobic exercise will be performed, through walking on flat terrain for
      five minutes in the first week, 10 minutes in the second, and 20 minutes in subsequent weeks,
      with intensity between 40-60% of the reserve heart rate and respecting the patients' symptoms
      (Spilmanns et al, 2021; Barker-Davies, 2020; Ribeiro, 2021) 3.6.1.1 Aerobic exercise
      intensity calculation

      Aerobic training intensity will be calculated by the modified BORG subjective exertion scale
      maintaining a score between 6 and 7 - with the progression respecting the patients' symptoms
      - and by the reserve heart rate:

      Target intensity = ((HRmax - HRrest) * 0.4 a 0.6) + HRrest First, maximum HR is determined
      using the Karvonen formula (220 - age) (KARVONEN, 1957).

      On the day of the first assessment, the resting HR will be determined after the participant
      has been at rest for five minutes in a sitting position, in an environment at 22 oC. By
      determining HRmax and HRrest, it will be possible to calculate the target range for each
      participant. For individuals using beta blockers, the modified BORG subjective exertion scale
      will be used, maintaining a score between 6 and 7. The intensity and progression will be
      based on the individual reports of the symptoms of all patients (Spilmanns et al, 2021;
      Barker-Davies, 2020; Ribeiro, 2021).

      3.6.2 INSPIRATORY MUSCLE TRAINING Patients from the TG will undergo IMT for six weeks,
      performing two sets of 30 repetitions daily using the device POWERbreathe classic medic®
      (POWERbreathe International Ltd., Southam, United Kingdom). MIP will be measured in all
      patients before the intervention as described earlier, and pa-tients will exercise at 40% MIP
      in the first week and 60% MIP in the subsequent five weeks. The patients will be instructed
      to inhale using the diaphragm muscle, trying to expand the rib cage to avoid using accessory
      muscles (Turqueto et al, 2021).

      A nose clip will be used to ensure patients breathe exclusively through the training device.
      All patients will have their training sessions supervised by the same physical therapist and
      will be encouraged to maintain their usual activities during the protocol (Turqueto et al,
      2021).

      Control patients (CG), who will undergo muscle strengthening and aerobic training during
      pulmonary rehabilitation, will receive the same IMT intervention using POWERbreathe classic
      medic® (POWERbreathe International Limited, Southam, United Kingdom) soon after completion of
      the 6-week experimental protocol, if the study has satisfactory results.

      STATISTICAL ANALYSIS Data normality will be tested through the Shapiro-Wilk test. To analyze
      the differences between groups, the t-test will be used for parametric data and the Wilcoxon
      test for non-parametric data. Bilateral tests will be performed using a significance level
      set at 5% (p < 0.05). Data will be analyzed using the SPSS 8.0 software and the results
      expressed as mean ± standard deviation or median and interquartile range.
    

Intervention name(s): TREATMENT GROUP (TG); CONTROL GROUP (CG)
Intervention type(s): Other; Other
Intervention description(s): In addition to muscle strengthening and aerobic exercise, patients from the TG will undergo IMT for six weeks, performing two sets of 30 repetitions daily using the device POWERbreathe classic medic® (POWERbreathe International Ltd., Southam, United Kingdom). MIP will be measured in all patients before the intervention as described earlier, and patients will exercise at 40% MIP in the first week and 60% MIP in the subsequent five weeks. The patients will be instructed to inhale using the diaphragm muscle, trying to expand the rib cage to avoid using accessory muscles A nose clip will be used to ensure patients breathe exclusively through the training device.; For six weeks the CG will perform muscle strengthening through a sit and stand up from a chair routine, abduction of upper and lower limbs, and rowing; three sets of 10 repetitions of each exercise will be performed. Elastic tubes will be used, with elasticity defined by color and indicating the greatest resistance the participant can endure with an effort between 4 and 8 on the OMNI-RES scale for perceived exertion.
In addition, aerobic exercise will be performed, through walking on flat terrain for five minutes in the first week, 10 minutes in the second week, and 20 minutes in the subsequent week, with intensity between 40-60% of the reserve heart rate and respecting the patients' symptoms.
Aerobic training intensity will be calculated by the modified BORG exertion scale maintaining a score between 6 and 7 - with the progression respecting the patients' symptoms - and by the reserve heart rate.
Other intervention name(s): inspiratory muscle training using the POWERbreathe Classic Medic® device; muscle strengthening; aerobic training; muscle strengthening; aerobic training
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants were split into two experimental groups:
CONTROL GROUP (CG): Pulmonary rehabilitation protocol comprising muscle strengthening and aerobic training; TREATMENT GROUP (TG): Pulmonary rehabilitation protocol comprising muscle strengthening, aerobic training, and inspiratory muscle training using the POWERbreathe Classic Medic® device.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: covid19; inspiratory muscle training (IMT); maximum inspiratory pressure (MIP); dynamic inspiratory muscle strength index (S-Index); inspiratory muscle endurance; respiratory physicaltherapy; pulmonary rehabilitation