Pulmonary Rehabilitation

Number: 0032

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses pulmonary rehabiliation.

1. Medical Necessity

   1. Aetna considers entry into a medically supervised outpatient pulmonary rehabilitation program medically necessary when all of the following criteria are met:

      1. Member has chronic pulmonary disease (including alpha-1 antitrypsin deficiency, asbestosis, asthma, emphysema, chronic airflow obstruction, chronic bronchitis, cystic fibrosis, fibrosing alveolitis, pneumoconiosis, pulmonary alveolar proteinosis, pulmonary fibrosis, pulmonary hemosiderosis, persistent pulmonary impairment from COVID-19, radiation pneumonitis), or other conditions that affect pulmonary function such as ankylosing spondylitis, bronchopulmonary dysplasia, Guillain-Barre' syndrome or other infective polyneuritis, lung cancer, muscular dystrophy, myasthenia gravis, paralysis of diaphragm, sarcoidosis, or scoliosis; and
      2. Member has dyspnea at rest or with exertion; and
      3. Member has a reduction in exercise tolerance that restricts the ability to perform activities of daily living and/or work; and
      4. Symptoms persist despite appropriate medical management; and
      5. Member has a moderate to severe functional pulmonary disability as evidenced by either of the following:
         
         
         • A maximal pulmonary exercise stress test under optimal bronchodilatory treatment which demonstrates a respiratory limitation to exercise with a maximal oxygen uptake (VO2max) equal to or less than 20 ml/kg/min, or about 5 metabolic equivalents (METS); or
         • Pulmonary function tests showing that either the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, or diffusion capacity for carbon monoxide (Dlco) is less than 60 % of that predicted; and
           
      6. Member is physically able, motivated and willing to participate in the pulmonary rehabilitation program and be a candidate for self-care post program; and
      7. Member does not have any concomitant medical condition that would otherwise imminently contribute to deterioration of pulmonary status or undermine the expected benefits of the program (e.g., symptomatic coronary artery disease, congestive heart failure, myocardial infarction within the last 6 months, dysrhythmia, active joint disease, claudication, malignancy).
   2. Aetna considers pulmonary rehabilitation medically necessary for persons receiving a medically necessary lung transplantation (see CPB 0597 - Heart-Lung Transplantation and CPB 0598 - Lung Transplantation).
   3. Aetna considers repeat pulmonary rehabilitation programs not medically necessary.  However, exceptions may be made for patients undergoing a repeat pulmonary rehabilitation program in connection with lung transplantation or lung volume reduction surgery.
   4. Aetna considers routine, non-skilled, or maintenance care not medically necessary, such as:
       
      1. Repetitive services for chronic baseline conditions; or
      2. When there is an inability to sustain gains; or
      3. When there is a plateau in patient's progress toward goals, such that there is minimal or no potential for further substantial progress; or
      4. When there is no overall improvement.

   5. Pulmonary rehabilitation is not considered medically necessary in persons who have very severe pulmonary impairment as evidenced by dyspnea at rest, difficulty in conversation (one-word answers), inability to work, cessation of most of all usual activities making them housebound and often limiting them to bed or chair with dependency upon assistance from others for most ADL.  According to available guidelines, persons with very severe pulmonary impairment are not appropriate candidates for pulmonary rehabilitation.

   Notes: 

   • A typical course of pulmonary rehabilitation extends for up to 6 weeks or 36 hours of therapy.
   • For lung transplant candidates, pulmonary rehabilitation typically begins when the member is listed for transplant, and continues for 6 weeks after transplantation, at which time the member is transitioned to a home exercise program.

2. Experimental and Investigational

   Aetna considers pulmonary rehabilitation experimental and investigational for all other indications (except for the ones listed above).

3. Policy Limitations and Exclusions

   Notes: 

   • Coverage of pulmonary rehabilitation may be subject to applicable limits on short-term rehabilitation therapies.  Please check benefit plan descriptions for details.
   • Most Aetna plans exclude coverage of exercise equipment.  Please check benefit plan descriptions for details.  Itemized charges for the use, rental, or purchase of exercise equipment may not be covered expenses under these plans.  This would include any charges for fitness center or health club memberships.

4. Related Policies

   • CPB 0597 - Heart-Lung Transplantation
   • CPB 0598 - Lung Transplantation

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
CPT codes covered if selection criteria are met:
94625	Physician or other qualified health care professional services for outpatient pulmonary rehabilitation; without continuous oximetry monitoring (per session)
94626	Physician or other qualified health care professional services for outpatient pulmonary rehabilitation; with continuous oximetry monitoring (per session)
Other CPT codes related to the CPB:
78580 - 78599	Diagnostic radiology, (eg, particulates) respiratory system
94010 - 94624, 94627 - 94799	Pulmonary laboratory medicine
HCPCS codes covered if selection criteria are met:
G0237	Therapeutic procedures to increase strength or endurance of respiratory muscles, face-to-face, one-on-one, each 15 minutes (includes monitoring)
G0238	Therapeutic procedures to improve respiratory function, other than described by G0237, one-on-one, face-to-face, per 15 minutes (includes monitoring)
G0239	Therapeutic procedures to improve respiratory function or increase strength or endurance of respiratory muscles, 2 or more individuals (includes monitoring)
S9473	Pulmonary rehabilitation program, non-physician provider, per diem
Other HCPCS codes related to the CPB:
A9300	Exercise equipment
ICD-10 codes covered if selection criteria are met:
C34.00 - C34.92	Malignant neoplasm of bronchus and lung [Lung cancer]
D86.0 - D86.9	Sarcoidosis
E84.0 - E84.9	Cystic fibrosis
E88.01	Alpha-1-antitrypsin deficiency
G65.0 - G65.2	Sequelae of inflammatry and toxic polyneuropathies
G70.00 - G70.9	Myasthenia gravis and other myoneural disorders
G71.00 - G71.9	Primary disorders of muscles
G72.0 - G72.9	Other and unspecified myopathies
J40 - J47.9	Chronic lower respiratory diseases
J60 - J70.9	Lung diseases due to external agents
J80 - J84.9	Other respiratory diseases principally affecting the interstitium
J85.0 - J86.9	Suppurative nerotic conditions of the lower respiratory track
M41.00 - M41.9	Scoliosis
M45.0 - M45.9	Ankylosing spondylitis
P27.0 - P27.9	Chronic respiratory disease originating in the perinatal period [bronchopulmonary dysplasia, pulmonary fibrosis]
R06.00 - R06.09	Dyspnea [at rest or with exertion]
U07.1	COVID-19
U09.9	Post COVID-19 condition, unspecified
Z76.82	Awaiting organ transplant status [when patient is listed for transplant]
Z94.2	Lung transplant status
ICD-10 codes contraindicated for this CPB:
C00.0 - C33, C37 - C96.9	Malignant neoplasm [not covered for pre-operative pulmonary rehabilitation, except lung cancer]
F17.200 - F17.299	Nicotine dependence [recent or has quit for less than 3 months]
I21.01 - I22.9	ST elevation (STEMI) and non-ST elevation (NSTEMI) myocardial infarction [within last 6 months]
I21.A1	Myocardial infarction type 2
I21.A9	Other myocardial infarction type
I25.10 - I25.9	Chronic ischemic heart disease [symptomatic]
I47.0 - I49.9	Paroxysmal tachycardia, atrial fibrillation and flutter and other cardiac arrhythmias
I50.20 - I50.9	Heart failure
I73.89 - I73.9	Other specified and unspecified peripheral vascular disease [claudication]
I82.0 - I82.91	Other venous embolism and thrombosis [claudication]
M00.00 - M25.9	Arthropathies [active]

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Background

Comprehensive pulmonary rehabilitation is an outpatient multi-disciplinary program directed to individuals with chronic pulmonary conditions and their families, usually by an inter-disciplinary team of specialists, in an effort to stabilize or reverse both the pathophysiology and psychopathology of their chronic pulmonary disease, with the goal of achieving and maintaining the individual's maximum level of functional capacity and independence in the community allowed by the patient's pulmonary handicap and overall life situation. Examples of conditions that may benefit from pulmonary rehabilitation include, but are not limited to, asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pre- or postoperative lung transplant or lung volume surgery or pulmonary fibrosis (interstitial lung disease).

The goal of pulmonary rehabilitation services is not to achieve maximum exercise tolerance, but rather a level of function that allows for the transfer of treatment from the clinic, hospital, or doctor to self-care in the home by the patient, the patient's family, or the patient's caregiver.  Unless the patient will be able to conduct ongoing self-care at home, there will be only temporary benefit from the pulmonary rehabilitation services.  The endpoint of treatment, therefore, is not when the patient achieves maximal exercise tolerance or stabilizes, but when the patient or his or her attendant is able to continue pulmonary rehabilitation at home.  To achieve sustained results, it is important that the patient continue with an at-home pulmonary rehabilitation regimen. 

Primary objectives of pulmonary rehabilitation include: help to restore the ability to function at the highest level of independence in regards to activities of daily living (ADLs); and improving day-to-day functioning and coping strategies.

Pulmonary rehabilitation components may include assessment of the individual, education for the individual and family, breathing exercises, respiratory muscle training, general exercise and strengthening programs, nutritional interventions, psychosocial support and/or lifestyle modification. It is usually conducted in an outpatient setting.

Chronic obstructive pulmonary disease (COPD) is a diagnosis best reserved for those individuals with chronic bronchitis or emphysema who have demonstrated airflow obstruction on pulmonary function testing.  Bronchial asthma is considered as a separate disorder, rather than being included under the term COPD; however, it is recognized that those with COPD may also have a component of asthma.  Pulmonary rehabilitation is most useful for patients with COPD; however, certain aspects of the program may be selected for patients with other symptomatic pulmonary disorders.

Supervised pulmonary rehabilitation programs have been shown to be an effective method to control and alleviate as much as possible the symptoms and pathologic complications of respiratory impairment and to teach how to achieve optimal capability for carrying out activities of daily living in appropriately selected patients.

The 3 primary objectives of pulmonary rehabilitation services are:

1. to control, reduce, and alleviate the symptoms and pathophysiologic complications of chronic pulmonary disease;
2. to train the patient how to reach the highest possible level of independent functioning for his or her activities of daily living within the limitations of the pulmonary disease; and
3. to train the patient to self-manage his or her daily living consistent with the pulmonary disease process to obtain the highest possible level of independent function.

The ideal candidate for pulmonary rehabilitation is one with moderate to moderately severe disease, stable on standard medical therapy, not distracted or limited by other serious or unstable medical conditions, willing and able to learn about his or her disease, and motivated to devote the time and effort necessary to benefit from a comprehensive care program.  Patients with very mild disease may not perceive their problem as severe enough to warrant a comprehensive care program, and patients with very severe disease may be too limited to benefit appreciably.  Pulmonary rehabilitation is not a primary mode of therapy for obstructive airway disease; therefore, patients should be stabilized on standard medical therapy before beginning the program.

Every pulmonary rehabilitation program is individualized for a specific patient's needs and should include a comprehensive initial evaluation, established goals, an explicit treatment plan consisting of specific modalities with the stated frequencies, anticipated duration, and periodic re-assessments at scheduled intervals.  A program developed in such a manner should be documented and results of the assessments recorded.

For many years, the standard of care for pulmonary patients included inactivity and bedrest, with patients considered as passive recipients of medical treatment.  The high incidence of impairment, disability, and handicap associated with COPD has led to the development of pulmonary rehabilitation programs.  Such programs aim to improve the patient's ability to carry out the activities of daily living and, thereby, to improve their quality of life.

Many patients with COPD can be diagnosed, worked-up, and medically managed by their primary care physician or pulmonary specialist with resultant improvement in symptoms without the need for pulmonary rehabilitation.  The goals of medical therapy are to slow the expected decline in lung function and, if possible, to improve lung function.  Once the patient has been stabilized using standard medical therapy, it is unlikely that much additional improvement in pulmonary function can be expected.  However, further efforts can be made by the physician to institute a rehabilitation program under his or her direction.  The success of such a treatment is strongly influenced by the physician’s interest and the participation of the patient and his or her family in following a program of education about the disease, avoidance of risk factors, cessation of smoking, reduction in exposure to pulmonary irritants, immunization prophylaxis for influenza and pneumococcus, a designed exercise training program, and control of secretions, all of which can be adequately accomplished without the need for a formal pulmonary rehabilitation program.  The benefits of such a pulmonary rehabilitation are most evident as changes in the quality of life.  The general philosophy of a program should be to encourage patients to assume responsibility for and to become active participants and partners in taking care of themselves.

An individualized exercise program directed by the COPD patient’s primary care physician or pulmonologist, focused on improving function and quality of life, can reduce respiratory symptoms and limitations and reduce hospitalizations.  The exercise program should be simple and task specific (e.g., walking, dressing, etc.).  A graded aerobic exercise program (e.g., walking, or bicycling, 20 mins 3 times weekly) may be helpful to prevent deterioration of physical condition and to improve the patient’s ability to carry out daily activities.  Pursed-lip breathing to slow the rate of breathing and abdominal breathing exercises to relieve fatigue of the accessory muscles of respiration may reduce dyspnea in some patients.  A home monitoring program, in which patients are asked to record the use of metered-dose inhalers (MDI) and symptoms, is useful.  A home peak flow-meter will provide an objective record of the severity of the obstruction.

Before the patient enters a formal rehabilitation program, an accurate diagnosis of COPD or other chronic pulmonary disease must be made.  Lung function tests will give an indication about the physical aspects of impairment caused by the disease.  The patient should have received physician-directed medical management with optimization of pulmonary function tests and still have symptoms of dyspnea which interferes with the activities of daily living and/or work.  For the purposes of evaluating the extent of the physical aspects of the disability and identifying limiting factors in the gas transport chain, it is essential that the patient undergo a true maximal exercise test according to physiologic criteria.

The initial assessment or evaluation by a pulmonary therapist should include:

1. a diagnostic work-up and evaluation of the patient’s rehabilitation potential;
2.  a detailed description of specific problems the patient has in performing daily activities;
3. chest X-ray or report review;
4. pulmonary function testing;
5. exercise testing that assesses oxygen consumption and oxygenation at rest and with exercise;
6. indication of a high level of motivation to participate in the program;
7. determination of the appropriate type of care for the given pulmonary disability (e.g., select appropriate modalities, establish frequency and expected duration, etc.);
8. setting of goals and objectives (e.g. improve strength, power, motion, flexibility, etc.); and 
9. anticipation of outcomes.

The initial assessment is lengthy since the patient's functional level needs to be evaluated and measured carefully before establishing an appropriate program.  As noted above, regular re-evaluations (about every 2 or 4 weeks) which are dependent on the frequency of the program and the severity of the patient's illness are required throughout the program.  The purpose is to measure progression (or regression) and set new goals, frequency of treatment, and anticipated duration.

Goals should be explicit and objectively measurable, e.g., progressively improve 6- or 12-min walk.  They also need to establish an appropriate length of time to achieve the anticipated outcome.

Appropriate candidates for pulmonary rehabilitation programs have pulmonary disabilities with limitation of functional status resulting in a reduction of exercise tolerance, an interference with the person's lifestyle and/or a restriction in the person's ability to perform the activities of daily living and/or work.  Pulmonary rehabilitation programs are not indicated for persons whose pulmonary stress test reveals that activities are not limited by dyspnea.

Pulmonary rehabilitation programs do not benefit persons with very severe pulmonary impairment as evidenced by dyspnea at rest, difficulty in conversation (one-word answers), inability to work, cessation of most of all usual activities making him/her housebound and often limited to bed or chair with dependency upon assistance from others for most ADLs.

Appropriate candidates should have quit smoking for at least 3 months.  This act reflects the patient's motivation and active commitment to a lifestyle change.  Patients who quit on the first day of the program frequently start smoking soon after the program is completed.

Candidates should have moderate to moderately severe functional pulmonary disability as evidenced by either:

1. pulmonary function tests showing that either the FEV1, FVC, FEV1/FVC, or Dlco is less than 60 % of that predicted; or
2. a maximal pulmonary exercise stress test under optimal bronchodilatory treatment that  demonstrates a respiratory limitation to exercise with a maximal oxygen uptake (VO2max) equal to or less than 20 ml/kg/min, or about 5 METS. 

This maximal pulmonary exercise stress test test should be performed using treadmill walking or cycle ergometer with monitoring of work load, heart rate, EKG, and determinations of blood gas composition at rest and during exercise.

Appropriate candidates for pulmonary rehabilitation programs should not have any concomitant medical condition that would otherwise imminently contribute to deterioration of pulmonary status or undermine the expected benefits of the program (e.g., symptomatic coronary artery disease, congestive heart failure, myocardial infarction within the last 6 months, dysrhythmia, active joint disease, claudication, and malignancy).  Candidates should not have another disabling or unstable condition which limits ability to participate fully and to concentrate on rehabilitation activities.

According to the American Association for Respiratory Care (AARC, 2002), potential contraindications to outpatient pulmonary rehabilitation include: acute cor pulmonale, ischemic cardiac disease, metastatic cancer, psychiatric disease that interferes with memory and compliance, renal failure, severe pulmonary dysfunction, severe cognitive deficit, and Significant hepatic dysfunction. The decision to provide or withhold outpatient pulmonary rehabilitation should be based on a thorough, individualized assessment.

Pulmonary rehabilitation programs are not appropriate for persons who refuse to participate, or have a strong history of medical noncompliance.

A supervised pulmonary rehabilitation program is completed once the progress notes indicate that the patient has acquired the skills to self-monitor unsupervised exercise, or documentation from progress notes indicates no potential for gain or the absence of progress in the improvement in functional capacity at any time during the program.  It should be noted that improvement in arterial blood gases and pulmonary function testing is not generally expected and is not required for measuring progress in a patient participating in a pulmonary rehabilitation program.

A typical course of pulmonary rehabilitation extends for up to 6 weeks or 36 hours of therapy.  Additional pulmonary rehabilitation may be considered necessary with documentation of progress in the initial 6 weeks or 36 hours of pulmonary rehabilitation; documentation that the patient's performance capacity is expected to improve; and documentation of an assessment that indicates that continuation of the supervised exercise training is necessary to enable the patient to reach an acceptable level of individual exercise tolerance consistent with the particular stage of that patient's disease.

The patient’s medical record should support the pulmonary rehabilitation services being rendered.  Documentation should include:

1. a dated description of treatment received for each scheduled visit;
2. periodic (usually at least every 5 visits) exercise testing demonstrating objective measurable findings of physical and functional status showing improvement from baseline assessments to substantiate progress achieved;
3. periodic (usually at least every 5 visits) assessment with revision and/or re-statement of short-term goals and treatment plan;
4. periodic (usually bi-weekly) team conference notes of individual goals and progress;
5. a treatment plan to attain goals with justification for continuing rehabilitation program, including frequency and duration; and
6. evidence of communication with referring physician.

Pulmonary rehabilitation programs are also appropriate for lung transplant candidates.  For lung transplant candidates, pulmonary rehabilitation typically begins when the member is listed for transplant, and continues for 6 weeks after transplantation, at which time the member is transitioned to a home exercise program.

Spruit and Wouters (2007) stated that pulmonary rehabilitation has been demonstrated to be an important part of the management of patients with COPD.  Exercise training is the corner stone of a comprehensive, multi-disciplinary pulmonary rehabilitation in COPD and has been shown to improve health-related quality of life and exercise capacity.  However, not every COPD patient responds well to pulmonary rehabilitation.  The authors noted that future studies should center on new modalities to conventional pulmonary rehabilitation programs to optimize its effects.  These new additions include endurance training and long-acting bronchodilators; endurance training and technical modalities (e.g., inspiratory pressure support and inspiratory muscle training); interval training; resistance training; transcutaneous neuromuscular electrical stimulation; and exercise training and supplements (e.g., oxygen, oral creatine supplementation, anabolic steroids and polyunsaturated fatty acids).  Currently, these new modalities of pulmonary rehabilitation have been reported to improve body composition, skeletal muscle function and sometimes exercise capacity.  Nevertheless, the translation to an improved health-related quality of life is lacking, and cost-effectiveness as well as long-term effects have not been examined.  Moreover, future studies should examine the effects of pulmonary rehabilitation in elderly patients with restrictive pulmonary diseases.

In a prospective, randomized, controlled study, Eaton et al (2009) determined if early pulmonary rehabilitation, commenced as an inpatient and continued after discharge, reduced acute health-care utilization.  Consecutive COPD patients (n = 397), admitted with an exacerbation, were screened: 228 satisfied the eligibility criteria, of whom 97 consented to randomization to rehabilitation or usual care.  Both intention-to-treat and per-protocol analyses were reported with adherence being defined a priori as participation in at least 75 % of rehabilitation sessions.  Participants were elderly with severe impairment of pulmonary function, poor health-related quality of life and high COPD-related morbidity.  The rehabilitation group demonstrated a 23 % (95 % confidence interval [CI]: 11 to 36 %) risk of re-admission at 3 months, with attendees having a 16 % (95 % CI: 0 to 32 %) risk compared with 32 % (95 % CI: 19 to 45 %) for usual care.  These differences were non-significant.  There were a total of 79 COPD-related re-admission days (1.7 per patient, 95 % CI: 0.6 to 2.7, p = 0.19) in the rehabilitation group, compared with 25 (1.3 per patient, 95 % CI: 0 to 3.1, p = 0.17) for the attendees and 209 (4.2 per patient, 95 % CI: 1.7 to 6.7) for usual care.  The body mass index, airflow obstruction, dyspnea and exercise capacity index showed a non-significant trend to greater improvement among attendees compared with those receiving usual care (5.5 (2.3) and 5.6 (2.7) at baseline, improving to 3.7 (1.9) and 4.5 (2.5), respectively, at 3 months).  No adverse effects were identified.  The authors concluded that early inpatient-outpatient rehabilitation for COPD patients admitted with an exacerbation was feasible and safe, and was associated with a non-significant trend towards reduced acute health-care utilization.

In a Cochrane review, Puhan et al (2009) evaluated the effects of pulmonary rehabilitation following COPD exacerbations on future hospital admissions (primary outcome) and other patient-important outcomes (mortality, health-related quality of life and exercise capacity).  Randomized controlled trials comparing pulmonary rehabilitation of any duration after exacerbation of COPD with conventional care were selected.  Pulmonary rehabilitation programs needed to include at least physical exercise.  Control groups received conventional community care without rehabilitation.  These researchers calculated pooled odds ratios (ORs) and weighted mean differences (WMD) using fixed-effects models.  They requested missing data from the authors of the primary studies.  A total of 6 trials (n = 219) were identified.  Pulmonary rehabilitation significantly reduced hospital admissions (pooled OR 0.13 [95 % CI: 0.04 to 0.35], number needed to treat (NNT) 3 [95 % CI: 2 to 4], over 34 weeks) and mortality (pooled OR 0.29 [95 % CI: 0.10 to 0.84], NNT 6 [95 % CI: 5 to 30] over 107 weeks).  Effects of pulmonary rehabilitation on health-related quality of life were well above the minimal important difference (WMD for dyspnea, fatigue, emotional function, and mastery domains of the Chronic Respiratory Questionnaire between 1.15 (95 % CI: 0.94 to 1.36) and 1.88 (95 % CI: 1.67 to 2.09) and between -9.9 (95 % CI: -18.05 to -1.73) and -17.1 (95 % CI: -23.55 to -10.68) for total, impact and activity limitation domains of the St. Georges Respiratory Questionnaire).  In all trials, pulmonary rehabilitation improved exercise capacity (60 to 215 meters in 6-min or shuttle walk tests).  No adverse events were reported (2 studies).  The authors concluded that evidence from small studies of moderate methodological quality suggested that pulmonary rehabilitation is a highly effective and safe intervention to reduce hospital admissions and mortality and to improve health-related quality of life in COPD patients after suffering an exacerbation.

An official statement of the American College of Physicians (ACP), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), and European Respiratory Society (ERS) (Qaseem et al, 2011) represents an update of the 2007 ACP clinical practice guideline on diagnosis and management of stable COPD and is intended for clinicians who manage patients with COPD.  The ACP, ACCP, ATS, and ERS recommend that clinicians should prescribe pulmonary rehabilitation for symptomatic patients with an FEV(1) less than 50 % predicted (Grade: Strong recommendation, moderate-quality evidence).  Clinicians may consider pulmonary rehabilitation for symptomatic or exercise-limited patients with an FEV(1) greater than 50 % predicted (Grade: Weak recommendation, moderate-quality evidence).

Schmidt-Hansen et al (2012) stated that the preferred treatment for lung cancer is surgery if the disease is considered resectable and the patient is considered surgically fit.  Pre-operative smoking cessation and/or pre-operative pulmonary rehabilitation might improve post-operative outcomes after lung cancer surgery.  The objectives of this systematic review were to determine the effectiveness of

1. pre-operative smoking cessation and
2. pre-operative pulmonary rehabilitation on peri- and post-operative outcomes in patients who undergo resection for lung cancer.  

These investigators searched MEDLINE, PreMedline, Embase, Cochrane Library, Cinahl, BNI, Psychinfo, Amed, Web of Science (SCI and SSCI), and Biomed Central.  Original studies published in English investigating the effect of pre-operative smoking cessation or pre-operative pulmonary rehabilitation on operative and longer-term outcomes in greater than or equal to 50 patients who received surgery with curative intent for lung cancer were included.  Of the 7 included studies that examined the effect of pre-operative smoking cessation (n = 6) and pre-operative pulmonary rehabilitation (n = 1) on outcomes after lung cancer surgery, none was randomized controlled trials and only 1 was prospective.  The studies used different smoking classifications, the baseline characteristics differed between the study groups in some of the studies, and most had small sample sizes.  No formal data synthesis was therefore possible.  The included studies were marked by methodological limitations.  On the basis of the reported bodies of evidence, it is not possible to make any firm conclusions about the effect of pre-operative smoking cessation or of pre-operative pulmonary rehabilitation on operative outcomes in patients undergoing surgery for lung cancer.

In a Cochrane review, Dowman and colleagues (2014) examined if PR in patients with interstitial lung disease (ILD) has beneficial effects on exercise capacity, symptoms, quality of life and survival compared with no pulmonary rehabilitation in patients with ILD.  These investigators searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (Ovid), EMBASE (Ovid), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO) and the Physiotherapy Evidence Database (PEDro) (all searched from inception to June 2014).  They also searched the reference lists of relevant studies, international clinical trial registries and respiratory conference abstracts to look for qualifying studies.  Randomized and quasi-randomized controlled trials in which pulmonary rehabilitation was compared with no pulmonary rehabilitation or with other therapy in people with ILD of any origin were included.  Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias.  Study authors were contacted to provide missing data and information regarding adverse effects.  A priori subgroup analyses were specified for participants with idiopathic pulmonary fibrosis (IPF) and participants with severe lung disease (low diffusing capacity or desaturation during exercise).  These researchers planned to subgroup according to training modality applied, but there were insufficient data.  A total of 9 studies were included, 6 of which were published as abstracts.  Five studies were included in the meta-analysis (86 participants who undertook PR and 82 control participants).  One study used a blinded assessor and intention-to-treat analysis.  No adverse effects of PR were reported.  Pulmonary rehabilitation improved the 6-minute walk distance with weighted mean difference (WMD) of 44.34 meters (95 % CI: 26.04 to 62.64 meters) and improved oxygen consumption (VO2) peak with WMD of 1.24 ml/kg/min-1 (95 % CI 0.46 to 2.03 mL/kg/min-1).  Improvements in 6-minute walk distance and VO2 peak were also seen in the subgroup of participants with IPF (WMD 35.63 meters, 95 % CI: 16.02 to 55.23 meters; WMD 1.46 ml/kg/min-1, 95 % CI: 0.54 to 2.39 ml/kg/min-1, respectively).  Reduced dyspnea (standardized mean difference (SMD) -0.66, 95 % CI: -1.05 to -0.28) following PR was also seen in the IPF subgroup (SMD -0.68, 95 % CI: -1.12 to -0.25).  Quality of life improved following PR for all participants on a variety of measures (SMD 0.59, 95 % CI: 0.20 to 0.98) and for the subgroup of people with IPF (SMD 0.59, 95 % CI: 0.14 to 1.03).  Two studies reported longer-term outcomes, with no significant effects of PR on clinical variables or survival at 3 or 6 months.  Available data were insufficient to allow examination of the impact of disease severity or exercise training modality.  The authors concluded that PR seemed to be safe for people with ILD.  Improvements in functional exercise capacity, dyspnea and quality of life are seen immediately following PR, with benefits also evident in IPF.  However, because of inadequate reporting of methods and small numbers of included participants, the quality of evidence was low to moderate.  Moreover, little evidence was available regarding longer-term effects of PR.

Individuals with COPD and Mild Symptoms

Rugbjerg et al (2015) stated that most guidelines recommend PR for patients with COPD and modified Medical Research Council dyspnea scale (mMRC) levels greater than or equal to 2, but the effectiveness of PR in patients with less advanced disease is not well established.  These researchers investigated the effects of PR in patients with COPD and mMRC less than or equal to 1.  The methodology was developed as a part of evidence-based guideline development and is in accordance with the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group.  These investigators identified randomized controlled trials (RCTs) through a systematic, multi-database literature search and selected RCTs comparing the effects of PR with usual care in patients with COPD and mMRC less than or equal to 1.  Predefined critical outcomes were health-related quality of life (HRQoL), adverse effects and mortality, while walking distance, maximal exercise capacity, muscle strength, and drop-outs were important outcomes.  Two authors independently extracted data, assessed trial eligibility and risk of bias, and graded the evidence.  Meta-analyses were performed when deemed feasible.  A total of 4 RCTs (489 participants) were included.  On the basis of moderate-quality evidence, these investigators found a clinically and statistically significant improvement in short-term HRQoL of 4.2 units (95 % CI: -4.51 to -3.89) on St George's Respiratory Questionnaire, but not at the longest follow-up.  They also found a statistically significant improvement of 25.71 m (95 % CI: 15.76 to 35.65) in the 6-minute walk test with PR; however, this improvement was not considered clinically relevant.  No difference was found for mortality, and insufficient data prohibited meta-analysis for muscle strength and maximal exercise capacity.  No adverse effects were reported.  The authors concluded that they found a moderate quality of evidence suggesting a small, significant improvement in short-term HRQoL and a clinically non-significant improvement in walking distance following PR in patients with COPD and mild symptoms.  This resulted in a weak recommendation of routine PR in these patients using the GRADE approach.

Prevention of Acute Exacerbations of COPD in Persons with Moderate, Severe, or Very Severe COPD

The American College of Chest Physicians and Canadian Thoracic Society guideline on “Prevention of acute exacerbations of COPD” (Criner et al, 2015) states that in patients with moderate, severe, or very severe COPD who have had an exacerbation greater than the past 4 weeks, the panel does not suggest PR to prevent acute exacerbations of COPD.

Non-Cystic Fibrosis Bronchiectasis

In a systematic review, Lee and colleagues (2017) examined the effect of PR (exercise and education) or exercise training (ET) on exercise capacity, health-related quality of life (HRQOL), symptoms, frequency of exacerbations, and mortality compared with no treatment in adults with non-cystic fibrosis bronchiectasis.  Computer-based databases were searched from their inception to February 2016; RCTs of PR or ET versus no treatment in adults with bronchiectasis were included.  Two reviewers independently extracted data and assessed methodological quality using the Cochrane risk-of-bias tool.  A total of 4 trials with 164 participants were included, with variable study quality.  Supervised out-patient PR or ET of 8 weeks improved incremental shuttle walk distance (WMD = 67 m; 95 % CI]: 52 to 82 m) and disease-specific HRQOL (WMD = -4.65; 95 % CI: -6.7 to -2.6 units) immediately after intervention, but these benefits were not sustained at 6 months.  There was no effect on cough-related quality of life (WMD = 1.3; 95 % CI: -0.9 to 3.4 units) or psychological symptoms.  Pulmonary rehabilitation commenced during an acute exacerbation and continued beyond discharge had no effect on exercise capacity or HRQOL.  The frequency of exacerbations over 12 months was reduced with out-patient ET (median of 2 versus 1; p = 0.013), but PR initiated during an exacerbation had no impact on exacerbation frequency or mortality.  The authors concluded that short-term improvements in exercise capacity and HRQOL were achieved with supervised PR and ET programs, but sustaining these benefits is challenging in people with bronchiectasis.  They stated that the frequency of exacerbations over 12 months was reduced with ET only.

Sarcoidosis

Lingner and associates (2015) stated that available data assessing the effectiveness of PR for patients with chronic sarcoidosis are scant; for Germany, there are none at all.  To gain information about the benefit of in-house PR for patients with chronic sarcoidosis and for the health care system, these investigators intended to collect data in a prospective multi-center "real-life" cohort trial – Prospective Catamnesis Study of Sarcoidosis in Pulmonary Rehabilitation – will evaluate a multi-modal 3-week inpatient PR program for adult patients with chronic sarcoidosis over a 1-year follow-up time.  Defined specific clinical measurements and tests will be performed at the beginning and the end of the rehabilitation.  In addition, questionnaires concerning HRQOL and the patients' symptoms will be provided to all patients.  Inclusion criteria will be referral to 1 of the 6 participating PR clinics in Germany for sarcoidosis and age between 18 and 80 years.  Patients will only be excluded for a lack of German language skills or the inability to understand and complete the study questionnaires.  To rule out seasonal influences, the recruitment will take place over a period of 1 year.  In total, at least 121 patients are planned to be included.  A descriptive statistical analysis of the data will be performed, including multivariate analyses.  The primary outcomes are specific HRQOL (St George's Respiratory Questionnaire) and exercise capacity (6-minute walk test).  The secondary outcomes are several routine lung function and laboratory parameters, dyspnea scores and blood gas analysis at rest and during exercise, changes in fatigue, psychological burden, and generic HRQOL (36-item Short Form Health Survey).  Funding was obtained on October 12, 2010; enrollment began on January 15, 2011 and was completed by January 14, 2012.  Results are anticipated late summer 2015.  The authors concluded that due to the large number of participants, they expect to obtain representative findings concerning the effectiveness of PR for patients with sarcoidosis and to provide a dataset of assessed objective and subjective short- and long-term changes due to PR.  They stated that the results should form the basis for the planning of a RCT.

Prevention of Acute Exacerbations of COPD in Persons with Moderate, Severe, or Very Severe COPD

Moore and colleagues (2017) noted that in previous systematic reviews (predominantly of RCTs), PR has been shown to reduce hospital admissions for acute exacerbations of COPD (AECOPD).  However, findings have been less consistent for cohort studies.  These investigators compared rates of hospitalized and general practice (GP)-treated AECOPD prior to and following PR.  Using anonymized data from the Clinical Practice Research Datalink and Hospital Episode Statistics, hospital admissions and GP visits for AECOPD were compared 1 year prior to and 1 year following PR in patients referred for PR.  Exacerbation rates were also compared between individuals eligible and referred for PR vs those eligible and not referred.  A total of 69,089 (64 %) of the patients with COPD in the cohort were eligible for PR.  Of these, only 6,436 (9.3 %) were recorded as having been referred for rehabilitation.  A total of 62,019 (89.8 %) were not referred, and 634 (0.98 %) declined referral.  When combining GP and hospital exacerbations, patients who were eligible and referred for PR had a slightly higher but not statistically significant exacerbation rate (2.83 exacerbations/patient-year; 95 % CI: 2.66 to 3.00) than those who were eligible but not referred (2.17 exacerbations/patient-year; 95 % CI: 2.11 to 2.24).  The authors concluded that the findings of this study showed that less than 10 % of patients who were eligible for PR were actually referred.  Patients who were eligible and referred for (but not necessarily completed) PR did not have fewer GP visits and hospitalizations for AECOPD in the year following PR compared with those not referred or compared with the year prior to PR.

Post-Operative Pulmonary Rehabilitation in Persons with Lung Cancer

Nici (2008) noted that benefits derived from comprehensive pulmonary rehabilitation, when applied to patients who have lung cancer, should have significant impact on both survival and health status.  Because pulmonary rehabilitation is known to improve exercise capacity, it is reasonable to expect that this treatment modality may provide more patients with a potential cure.  In addition, improvement in symptoms and quality of life can prove critically important when long-term survival is not an outcome that can be impacted on.  Studies thus far support the value of this treatment modality in the global approach to patients who have lung cancer.  The author stated that future well-designed clinical trials will need to corroborate these findings.

Shannon (2010) stated that over the last decade, evidence-based support for pulmonary rehabilitation in the management of patients with chronic lung disease has grown tremendously.  A beneficial role of pulmonary rehabilitation has been largely shown among patients with COPD and in patients with pulmonary emphysema enlisted for lung volume reduction surgery.  In these settings, significant reductions in dyspnea, and improvements in exercise performance and health-related quality of life have been clearly demonstrated following a program of pulmonary rehabilitation.  Pulmonary rehabilitation is often advocated as an adjunctive intervention in patients with cancer; however, the benefits of this intervention in the cancer setting, particularly in the peri-operative setting for lung cancer, are only recently emerging.  The author summarized these investigations and highlighted ongoing controversies regarding the utility of pulmonary rehabilitation in the surgical and medical management of patients with lung cancer.  Recent small studies suggest that pulmonary rehabilitation may favorably impact lung cancer management by improving a variety of clinically meaningful outcomes such as performance status, chemotherapy-related fatigue, oxygen consumption, exercise tolerance, and health-related quality of life.  These findings, although intriguing, have not been investigated in any large, controlled trials to determine their impact, if any, on surgical resectability and outcome or on tolerance to aggressive chemo-radiation therapy regimens.  The author concluded that pulmonary rehabilitation shows promise as a therapeutic intervention in the management of lung cancer; however, well-designed, adequately powered studies are needed to examine outstanding questions regarding its exact role in guiding lung cancer management.

In a pilot, randomized, single-blinded study, Morano et al (2013) examined the effect of 4 weeks of pulmonary rehabilitation (PR) versus chest physical therapy (CPT) on the pre-operative functional capacity and post-operative respiratory morbidity of patients (n = 24) undergoing lung cancer resection.  Patients were randomly assigned to receive PR (strength and endurance training) versus CPT (breathing exercises for lung expansion).  Both groups received educational classes.  Main outcome measures were functional parameters assessed before and after 4 weeks of PR or CPT (phase 1), as well as pulmonary complications assessed after lung cancer resection (phase 2).  A total of 12 patients were randomly assigned to the PR arm and 12 to the CPT arm.  Three patients in the CPT arm were not submitted to lung resection because of inoperable cancer.  During phase 1 evaluation, most functional parameters in the PR group improved from baseline to 1 month: FVC (1.47 L [1.27 to 2.33 L] versus 1.71 L [1.65 to 2.80 L], respectively; p = 0.02); percentage of predicted FVC (FVC %; 62.5 % [49 % to 71 %] versus 76 % [65 % to 79.7 %], respectively; p < 0.05); 6-minute walk test (425.5 ± 85.3 m versus 475 ± 86.5m, respectively; p < 0.05); maximal inspiratory pressure (90 ± 45.9 cm H(2)O versus 117.5 ± 36.5 cm H(2)O, respectively; p < 0.05); and maximal expiratory pressure (79.7 ± 17.1 cm H(2)O versus 92.9 ± 21.4 cm H(2)O, respectively; p < 0.05).  During phase 2 evaluation, the PR group had a lower incidence of post-operative respiratory morbidity (p = 0.01), a shorter length of post-operative stay (12.2 ± 3.6 days versus 7.8 ± 4.8 days, respectively; p = 0.04), and required a chest tube for fewer days (7.4 ± 2.6 days versus 4.5 ± 2.9 days, respectively; p = 0.03) compared with the CPT arm.  The authors concluded that these findings suggested that 4 weeks of PR before lung cancer resection improved pre-operative functional capacity and decreased the post-operative respiratory morbidity.  The findings from this small pilot study need to be validated by well-designed studies.

In a joint consensus statement by the American Thoracic Society and the European Respiratory Society (2015) stated that "PR has demonstrated effectiveness for several respiratory conditions other than COPD. Randomized controlled trials demonstrating its beneficial effects on exercise capacity, symptoms, and/or health-related quality of life are available in interstitial lung disease, bronchiectasis, asthma, cystic fibrosis, lung transplantation, lung cancer, and pulmonary hypertension."

Lai and colleagues (2017) conducted a RCT to assess the impact of a preoperative  1-week, systematic, high-intensity inpatient exercise regimen on patients with lung cancer who had risk factors for post-operative pulmonary complications (PPCs).  The investigators conducted a RCT with 101 subjects of a pre-operative, 7-day systematic, integrated, high-intensity pulmonary exercise regimen.  The control group received standard pre-operative care.  The investigators analysed the occurrence of PPCs in both groups as the primary outcome; other outcomes included changes in blood gas, quality of life (QOL), peak expiratory flow rate, the 6-min walk distance (6MWD) and others.  The 6MWD showed an increase of 22.9 ± 25.9 m in the intervention group compared with 4.2 ± 9.2 m in the control group, giving a between-group difference of 18.7 m (95 % CI: 8.8 to 28.6; p < 0.001); the peak expiratory flow increased by 25.2 ± 24.6 l/min, compared with 4.2 ± 7.7 l/min (between-group difference: 21.0 m, 95 % CI: 7.2 to 34.8; p = 0.003).  The intervention group had a shorter average total (15.6 ± 3.6 versus 17.7 ± 5.3 days, p = 0.023) and post-operative LOS (6.1 ± 3.0 versus 8.7 ± 4.6 days, p = 0.001) than the control group; the incidence of PPCs (9.8 %, 5/51 versus 28.0 %, 14/50, p = 0.019) was significantly lower.  A multi-variable analysis of the risk of PPCs identified short-term rehabilitation intervention to be an independent risk factor (OR = 0.156, 95 % CI: 0.037 to 0.649, p = 0.011).  The investigators concluded that the study results suggested that a systematic, high-intensity pulmonary exercise program was a practical strategy when performed pre-operatively in patients with lung cancer with risk factors for PPCs.

In a retrospective, observational study, Zhou and colleagues (2020) examined the effectiveness and cost minimization of comprehensive PR (CPR) in lung cancer patients who underwent surgery.  This trial was based on medical records with 2,410 lung cancer patients who underwent an operation with/without CPR during the peri-operative period.  Variables including clinical characteristics, LOS, PPCs, and hospitalization expenses were compared between the intervention group (IG) and control group (CG).  The CPR regimen consists of inspiratory muscle training (IMT), aerobic endurance training, and pharmacotherapy.  Propensity score matching analysis was carried out between the 2 groups, and the ratio of matched patients was 1:4.  Finally, 205 cases of IG and 820 cases of CG in the matched cohort of this study were identified.  The post-operative hospital LOS [median of 5; inter-quartile range [IQR] of 4 to 7 days versus 7 (4 to 8) days, p < 0.001] and drug expenses [7,146 (5411-8987) versus 8,253 (6,048 to 11,483) ¥, p < 0.001] in the IG were lower compared with the CG.  Furthermore, the overall incidence of PPCs in the IG was reduced compared with the CG (26.8 % versus 36.7 %, p = 0.008), including pneumonia (10.7 % versus 16.8 %, p = 0.035) and atelectasis (8.8 % versus 14.0 %, p = 0.046).  Multi-variable analysis showed that CPR intervention (OR = 0.655, 95 % CI: 0.430 to 0.865, p = 0.006), age greater than or equal to 70 years (OR = 1.919, 95 % CI: 1.342 to 2.744, p < 0.001), smoking (OR = 2.048, 95 % CI: 1.552 to 2.704, p < 0.001) and COPD (OR = 1.158, 95 % CI: 1.160 to 2.152, p = 0.004) were related to PPCs.  The authors concluded that the findings of this retrospective cohort study revealed a lower PPC rate and the shorter post-operative LOS in the patients receiving CPR, showing the clinical value of CRP as an effective strategy for surgical lung cancer patients with risk factors.

The authors stated that this study had several drawbacks.  First, it was a retrospective cohort study.  The nature of this study may lead to the unmeasured or residual confounding between the 2 groups, even though these researchers performed PSM analysis that could help to reduce the bias.  Another drawback that should be noticed was the potential residual confounders, including smoking status and COPD, which may confound these findings.  It would have been better to stratify them according to smoking index and COPD severity in baseline data and regression analysis, but unfortunately, due to the limited data the authors obtained, further stratified analysis concerning smoking status or COPD was unable to be completed.  Given potentially poor records of some clinical data and the subjective bias of recorders, the statistical complications rate may be lower than the real situation; thus this study could not reflect real-world information.  Second, the study participants were recruited from a single regional medical center, and further research needs to confirm whether these findings are universally applicable.  Third, more variables, including QOL, should be included in the analysis to better examine the effectiveness of the CPR regimen.

An UpToDate review on “Pulmonary rehabilitation” (Celli, 2020) states that “Patients with lung cancer often experience muscle weakness, deconditioning, fatigue, and anxiety, which may be compounded by the effects of underlying COPD.  Limited data suggest that pulmonary rehabilitation is associated with benefits in walking endurance, peak exercise capacity, dyspnea, and fatigue”.  

Mao and colleagues (2021) noted that PR is one meaningful way of improving exercise tolerance and pulmonary function; therefore, it may reduce post-operative complications and mortality of pulmonary resection.  These investigators refreshed the data and conducted a systemic analysis.  They searched PubMed, Web of Science, and Embase using "lung OR pulmonary" AND "operation OR resection OR surgery" AND "rehabilitation or exercise".  The cut-off date was September 30, 2020.  The publications were filtrated, and data were extracted from all selected studies by 2 reviewers.  Review Manger 5.1 and the fixed or random regression model were used for calculating the pooled OR.  A total of 13 publications were included in this review – 5 publications reported mortality, 9 reported post-operative complications, and 7reported post-operative pulmonary complications.  The pooled OR of mortality was 1.32 [95 % CI: 0.54 to 3.23] for the PR group, the pooled OR of post-operative complications was 0.62 (95 % CI: 0.49 to 0.79) for the PR group, and the pooled OR of post-operative pulmonary complications was 0.39 (95 % CI: 0.27 to 0.56) for the PR group.  Subgroup analysis revealed the peri-operative PR was the most important part.  The authors concluded that PR may not affect the mortality of pulmonary resection patients; however, it could decrease the number of post-operative complications, especially pulmonary complications.  Peri-operative PR was the most important part of the program.

Long COVID-19

Interim guidance from the American Thoracic Society and European Respiratory Society (Spruit, et al., 2020) state: "The international task force suggests that COVID-19 survivors with pre-existing/ongoing lung function impairment at 6–8 weeks following hospital discharge should receive a comprehensive pulmonary rehabilitation programme consistent with established international standards, compared to no pulmonary rehabilitation programme."

The Italian Position Paper on “The role of respiratory rehabilitation in the COVID-19 crisis” (Vitacca et al, 2020) stated that “… due to still limited and evolving knowledge of COVID-19, there are few recommendations concerning the need in respiratory rehabilitation and physiotherapy interventions”.

Siddiq et al (2020) stated that the novel SARS-coronavirus-2 disease 19 (COVID-19) pandemic primarily affects the respiratory system.  Elderly individuals with co-morbidity are severely affected.  Survivors weaned from mechanical ventilation are at a higher risk of developing post-intensive care syndrome (PICS).  This review, based on 40 recent publications, highlighted PR in COVID-19.  There is a paucity of high-quality research on this topic; however, rehabilitation societies including the Turkish Society of Physical Medicine and Rehabilitation have issued PR recommendations in COVID-19 pneumonia with productive cough can benefit from diaphragmatic breathing, pursed-lip breathing, and resistance-breathing training.  Besides, those in mechanical ventilation and post-PICS COVID-19 cases, oxygen therapy, early mobilization, airway clearance, aerobic exercise, gradual-graded limb muscle resistance exercise, nutritional and psychological interventions should be considered.  During PR, careful evaluation of vital signs and exercise-induced symptoms is also needed.  When in-person PR is not possible, tele-rehabilitation should be explored.  Moreover, these researchers stated that the long-term effects of PR in COVID-19 need further evaluation.

Chikhanie et al (2021) noted that some COVID-19 patients develop respiratory failure requiring admission to intensive care unit (ICU). In a retrospective study, these researchers examined the effects of PR post-ICU in COVID-19 patients.  A total of 21 COVID-19 patients were evaluated pre- and post-PR and compared to a non-COVID-19 group of 21 patients rehabilitated after ICU admission due to respiratory failure.  PR induced greater 6-min walking test (6MWT) improvement in COVID-19 patients (+205 ± 121 m) than in other respiratory failure patients post-ICU (+93 ± 66 m).  The sooner PR was performed post-ICU, the better patients recovered.  The authors concluded that compared to non−COVID-19 respiratory patients, severe COVID-19 patients needed prolonged ICU stay and intubation, therefore had more functional impairment post-ICU, but recovered better following PR.  However, the recovery was limited with significant physical and psychosocial impairment remaining, possibly requiring longer rehabilitation, but the sooner patients were admitted post-ICU, the better they recovered.  This suggested that some aspects of PR could be initiated while in the ICU or the pulmonary ward.  Moreover, these researchers stated that further controlled and long-term studies are needed to better understand the role of PR post−COVID-19.  The authors stated that this study had several drawbacks.  First, the small sample size of COVID-19 patients (n = 21) who were rehabilitated.  Second, the lack of a control group of COVID-19 patients post-ICU who were not rehabilitated.  Third, the availability of 6MWT data only post-PR in the group of non-COVID-19 patients retrospectively analyzed as comparative group.

Zampogna et al (2021) noted that in hospitalized patients recovering from COVID-19, high prevalence of muscle weakness and physical performance impairment has been observed.  These researchers examined the effectiveness of PR in these subjects in a real-life setting.  They carried out retrospective data analysis of patients recovering from COVID-19, including those requiring assisted ventilation or oxygen therapy, consecutively admitted to an in-patient PR program between April 1 and August 15, 2020.  Short Physical Performance Battery (SPPB: primary outcome), Barthel Index (BI), and 6MWT were evaluated as outcome measures.  Data of 140 patients were analyzed.  After rehabilitation, patients showed improvements in SPPB {from: (median inter-quartile range [IQR]) 0.5 (0 to 7) to 7 (4 to 10), p < 0.001} and BI (from 55 [30 to 90] to 95 [65 to 100], p < 0.001), as well as in other assessed outcome measures.  The proportion of patients unable at admission to stand, rise from a chair and walk was significantly reduced (p < 0.00).  The authors concluded that PR was possible and effective in patients recovering from COVID-19.  Moreover, these researchers stated that these findings may be useful to guide clinicians taking care of patients surviving COVID-19 infection.

The authors stated that this study had several drawbacks.  For safety reasons, it was impossible to perform standard respiratory muscle or lung function tests, including the assessment of diffusion capacity.  Hence, these investigators were unable to define to what extent the decline in physical performance observed at admission could be ascribed to impairment in lung or respiratory muscle function.  The results of an uncontrolled study may be difficult to interpret because these investigators could suppose a positive effect in the long-term follow-up of these patients without a rehabilitative intervention.  A control population not performing any activity would be unethical given the undisputed benefits of PR or simple physical activity.  One possible solution to this dilemma could be a trial with early versus delayed rehabilitation in post-COVID-19 patients.  Furthermore, this study could suffer from low external validity due to the restrictive inclusion criteria that limited the study to patients without functional limitations before COVID-19 so as to focus on the direct effect of the virus on muscle and functional ability, reducing confounding effects.

Boutou et al (2021) discussed long COVID-19 pulmonary sequelae and management considerations. The authors stated that various national and international medical associations suggest that patients who have recovered from COVID-19 and present with limitation of their physical activity, reduction of their QOL, and/or associated symptoms including shortness of breath, fatigue, pain, and/or weakness of the upper and lower extremities may benefit from inclusion in PR programs. The optimal structure and duration of these programs and the most appropriate time-point of implementation, remain to be determined in the context of future, large RCTs.  These researchers stated that an evidence-based, multi-disciplinary team approach for phenotypic characterization of those individuals who will most likely benefit from timely therapeutic interventions is needed.

Venkatesan (2021) discussed the NICE guideline on long COVID and stated that the NICE guideline has been welcomed by healthcare professionals, but certain gaps are evident, and it will be crucial to fill them as soon as possible.  For example, although the guidance acknowledges the importance of multi-disciplinary rehabilitation for the management of patients post COVID, Sally Singh (University of Leicester, Leicester, UK) pointed out that rehabilitation programs should be individualized and adapted to accommodate the needs of the patient.  The British Lung Foundation also called for more detail in the guideline regarding rehabilitation resources since these will play a crucial role in recovery, commenting that “we particularly need details on who would benefit from rehabilitation, and what kind they should have.  We [also] need to ensure there is capacity in community rehabilitation services to help people with long COVID, since existing services might struggle to meet extra demand”.  They continued, “it's important the guideline continues to evolve so we can ensure the best possible care for anyone struggling”.

Fugazzaro et al (2022) noted that increasing numbers of individuals suffer from post-acute COVID-19 syndrome (PACS), which manifests with persistent symptoms, the most prevalent being dyspnea, fatigue, and musculoskeletal, cognitive, and/or mental health impairments.  In a systematic review, these investigators examined the effectiveness of rehabilitation interventions for individuals with PACS.  They searched the Medline, Embase, Cochrane Register of Controlled Trials, CINHAL, Scopus, Prospero, and PEDro databases and the International Clinical Trials Registry Platform for RCTs up to November 2021.  These researchers screened 516 citations for eligibility, i.e., trials that included individuals with PACS exposed to exercise-based rehabilitation interventions; 5 RCTs were included, totaling 512 subjects (aged 49.2 to 69.4 years, 65 % men).  Based on the revised Cochrane risk-of-bias tool (RoB 2.0), 2 RCTs had "low risk of bias", and 3 were in the "some concerns" category.  A total of 3 RCTs compared experimental rehabilitation interventions with no or minimal rehabilitation, while 2 compared 2 active rehabilitation interventions.  Rehabilitation appeared to improve dyspnea, anxiety, and kinesiophobia.  Results on pulmonary function were inconsistent, while improvements were detected in muscle strength, walking capacity, sit-to-stand performance, and QOL.  The authors concluded that pending on the outcomes of further studies based on qualitatively sound designs, these preliminary findings appeared to advocate for rehabilitation interventions to lessen disability due to PACS.

The authors stated that this review had several drawbacks.  First, the outcome measures used in the RCTs included were highly heterogeneous.  Second, some of the reports lacked complete data.  Both these limitations prevented these investigators from performing a meta-analysis.  Third, despite the comprehensive search strategy adopted, it was possible that these researchers did not identify all the existing reports of trials that would have been eligible for inclusion (e.g., reports in original languages other than those known by the research team).  In addition, although these investigators contacted all the corresponding authors of the reports with missing data and sent them follow-up emails if they did not answer, not all the missing data could be retrieved from the corresponding authors; therefore, a complete description of the study procedures, interventions, and results was not possible.  Fourth, these researchers found a paucity of trials examining the effectiveness of rehabilitation in PACS; the vast majority of the studies retrieved focused on the acute phase of COVID-19.  These researchers noted that the results of this review encouraged the implementation of rehabilitation in patients with PACS, as its effectiveness appeared to be demonstrated, although not always consistently, in all the domains examined by the trials included in this review.  However, as only 5 RCTs were included, and some of them involved a small number of subject or raised some concern regarding their internal validity, it is possible that future research will come to different conclusions.  Moreover, as individuals with major post-COVID sequelae such as cerebrovascular disease were frequently not enrolled in the trials included in this review, the generalizability of these findings to a wider PACS population is not guaranteed.  Furthermore, the average age of the subjects in the included studies was relatively high, limiting the information available on the effectiveness of rehabilitation in younger PACS individuals.  Finally, only 1 trial recorded the adverse events (AEs) associated with experimental rehabilitation, in spite of the relevance of this information to clinicians, who, in the absence of strong evidence, must balance elements for and against when indicating what rehabilitation is to be prescribed.

Nopp et al (2022) stated that COVID-19 patients face the risk of long-term sequelae including fatigue, breathlessness, and functional limitations; PR has been recommended, although formal studies examining the effect of rehabilitation in COVID-19 patients are lacking.  In a prospective, observational, cohort study, these investigators examine the outcomes of patients admitted to an outpatient PR center due to persistent symptoms after COVID-19.  The primary endpoint was change in 6-min walk distance (6MWD) after undergoing a 6-week inter-disciplinary individualized PR program.  Secondary endpoints included change in the post-COVID-19 functional status (PCFS) scale, Borg dyspnea scale, Fatigue Assessment Scale, and QOL.  Furthermore, changes in pulmonary function tests were examined.  Of 64 patients undergoing PR, 58 patients (mean age of 47 years, 43 % women, 38 % severe/critical COVID-19) were included in the per-protocol-analysis.  At baseline (i.e., in mean of 4.4 months after infection onset), mean 6MWD was 584.1 m (± 95.0), and functional impairment was graded in median at 2 (IQR, 2 to 3) on the PCFS.  On average, patients improved their 6MWD by 62.9 m (± 48.2, p < 0.001) and reported an improvement of 1 grade on the PCFS scale.  Accordingly, these researchers observed significant improvements across secondary endpoints including presence of dyspnea (p < 0.001), fatigue (p < 0.001), and QOL (p < 0.001).  Also, pulmonary function parameters (FEV1, lung diffusion capacity, inspiratory muscle pressure) significantly increased during PR.  The authors concluded that in patients with long COVID, exercise capacity, functional status, dyspnea, fatigue, and QOL improved after 6 weeks of personalized interdisciplinary PR.  Moreover, these researchers stated that future studies are needed to establish the optimal protocol, duration, and long-term benefits as well as cost-effectiveness of PR.

The authors stated that this study had several drawbacks.  First, no causal role of rehabilitation can be assumed with certainty due to the observational study design.  However, the conduct of a RCT on the effect of rehabilitation was considered unethical due to the lack of clinical equipoise; thus, the observed improvement in the primary and secondary endpoints might also be due to the normal recovery process or regression to the mean.  However, given that patients went through outpatient rehabilitation in mean 4.4 months after the infection, causal beneficial effects of this 6-weeks individualized PR program appeared to be a reasonable assumption.  Second, this trial was limited by missing values for some of the secondary outcomes.  Third, these findings could not be generalized to the total population of COVID-19 survivors, as the study population was relatively young and had a high proportion of highly educated individuals who likely had a good healthcare provider network that referred them to outpatient rehabilitation without clear guidelines at that time.  Fourth, the limited number of patients hindered subgroup analysis to examine differences in outcome and course of the disease stratified by patient characteristics (e.g., severity of COVID-19 or primary symptom of long COVID).

Soril et al (2022) stated that multi-disciplinary rehabilitation is recommended for individuals with post-acute sequelae of COVID-19 infection (i.e., symptoms 3 to 4 weeks after acute infection).  There are emerging reports of use of PR in the post-acute stages of COVID-19, however the appropriateness of PR for managing post-COVID symptoms remains unclear.  These investigators stated that to offer practical guidance with regards to post-COVID PR, a greater understanding of the clinical effectiveness literature is needed.  They carried out a rapid review of the published literature.  An electronic database search of the literature published between July 1, 2020 and June 1, 2021 was conducted in Medline, PubMed, and Embase.  Primary studies examining the clinical effectiveness of PR for individuals with post-COVID symptoms were included.  A total of 9 studies examining the effectiveness of PR were identified; most were small, experimental or quasi-experimental studies, including 1 RCT, and were primarily of low quality.  After attending PR, all studies reported improvements in exercise capacity, pulmonary function, and/or QOL for individuals with post-COVID symptoms who had been hospitalized for their acute COVID-19 infection.  Few studies examined changes in post-COVID symptom severity or frequency and, of these, improvements in dyspnea, fatigue, anxiety and depression were observed following PR.  Furthermore, no studies examined non-hospitalized patients or long-term outcomes beyond 3 months after initiating PR.  The authors concluded that evidence examining PR for patients with post-COVID symptoms is emerging; yet limited and of uncertain quality.  A challenge to understanding the potential benefit of post-COVID PR is the current limited knowledge of the long-term trajectory of post-COVID symptoms.  It is unclear if natural recovery occurs over time and, if so, at what rate and to what extent.  In addition, the appropriateness and effectiveness of PR versus other forms of rehabilitation for post-COVID conditions is unknown.  Such comparative studies are needed to better elucidate the ideal form of rehabilitation for this growing patient population.

On behalf of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Yelin et al (2022) provided evidence-based recommendations for the assessment and management of individuals with persistent symptoms after acute COVID-19 infection and provided a definition for this entity, termed “long COVID”.  These investigators conducted a literature search on studies addressing epidemiology, symptoms, assessment, and treatment of long COVID.  The recommendations were grouped by these headings and by organ systems for assessment and treatment.  Symptoms were reviewed by a search of the available literature.  For assessment recommendations, these researchers carried out a diagnostic meta-analysis; however, no studies provided relevant results.  For treatment recommendations, these investigators conducted a systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.  They examined patient-related outcomes (PROs), including QOL, return to baseline physical activity, and return to work.  Quality assessment of studies included in the systematic review was provided according to study design.  The authors provided the following recommendations:

• Evidence was insufficient to provide any recommendation other than conditional guidance.
• The panel recommended considering routine blood tests, chest imaging, and pulmonary functions tests for patients with persistent respiratory symptoms at 3 months.  Other tests should be performed mainly to exclude other conditions according to symptoms.
• For management, no evidence-based recommendations could be provided.  Physical and respiratory rehabilitation should be considered.
• On the basis of limited evidence, the panel suggested designing high-quality, prospective clinical studies/trials, including a control group, to further examine the assessment and management of individuals with persistent symptoms of COVID-199.

Furthermore, an UpToDate review on “Pulmonary rehabilitation” (Celli, 2022) states that “Preliminary results suggest that pulmonary rehabilitation is of benefit in patients with respiratory involvement from COVID-19 who remain symptomatic after the acute episode … Individuals with other chronic lung diseases, such as interstitial lung disease, bronchiectasis, cystic fibrosis, asthma, pulmonary artery hypertension, lung cancer, persistent respiratory symptoms post COVID-19, and lung transplantation, may also derive benefit from pulmonary rehabilitation, although supportive data is more limited”.

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References