Reviews

Pulmonary rehabilitation in interstitial lung diseases:

A review of the literature
Krzysztof Wytrychowski1,A–D,F, Anna Hans-Wytrychowska2,A,B,D,E, Paweł Piesiak3,B,C,E,
Marta Majewska-Pulsakowska4,A–E, Krystyna Rożek-Piechura5,E,F
1
Department and Clinic of Internal Medicine, Pneumonology and Allergology, Wroclaw Medical University, Poland
2
Department of Family Medicine, Wroclaw Medical University, Poland
3
Department and Clinic of Pulmonology and Lung Cancers, Wroclaw Medical University, Poland
4
Department and Division of Medical Rehabilitation, Wroclaw Medical University, Poland
5
Department of Rehabilitation in Internal Diseases, University School of Physical Education, Wrocław, Poland

A – research concept and design; B – collection and/or assembly of data; C – data analysis and interpretation;
D – writing the article; E – critical revision of the article; F – final approval of the article

Advances in Clinical and Experimental Medicine, ISSN 1899–5276 (print), ISSN 2451–2680 (online) Adv Clin Exp Med. 2020;29(2):257–264

Address for correspondence

Krzysztof Wytrychowski
Abstract
E-mail: anhw@op.pl There are more than 200 different diseases classed as interstitial lung diseases (ILDs). For epidemiological
and practical purposes, ILDs are classified into diseases of known and unknown etiology. The aim of this
Funding sources
None declared
review is to evaluate our current knowledge about the efficacy and safety of pulmonary rehabilitation (PR)
in patients with ILDs. Other issues, such as ILD pathogenesis, prevalence and comorbidity, are also elaborated
Conflict of interest in the review. Pulmonary rehabilitation is an important part of comprehensive care for patients with ILDs.
None declared In comparison to PR for patients with chronic pulmonary obstructive disease (COPD), the number of clinical
studies concerning PR for patients with ILDs is small. The majority of trials have been performed in relatively
small groups of patients. The principles of PR in this group of patients are the same as for patients with COPD.
Received on August 24, 2018 Exercise-induced desaturation is frequently observed during PR, which is the main source of complications
Reviewed on December 2, 2018
Accepted on December 12, 2019 in patients with ILDs. Major differences between ILD and COPD patients include poorer exercise tolerance
and faster development of respiratory failure in patients with ILDs.
Published online on February 26, 2020
Key words: pulmonary rehabilitation, airway management, interstitial lung diseases

Cite as
Wytrychowski K, Hans-Wytrychowska A, Piesiak P, Majewska-
Pulsakowska M, Rożek-Piechura K. Pulmonary rehabilitation
in interstitial lung diseases: A review of the literature.
Adv Clin Exp Med. 2020;29(2):257–264.
doi:10.17219/acem/115238

DOI
10.17219/acem/115238

Copyright
Copyright by Author(s)
This is an article distributed under the terms of the
Creative Commons Attribution 3.0 Unported (CC BY 3.0)
(https://creativecommons.org/licenses/by/3.0/)
258 K. Wytrychowski et al. Rehabilitation in interstitial lung diseases

The pathogenesis and prevalence Management

of interstitial lung diseases Due to the different pathogenic mechanisms, treatment
Interstitial lung diseases (ILDs) constitute a heteroge- for ILDs varies depending on the diagnosis. In the case
neous group of about 200 diseases characterized by acute of a known cause, such as for example exposure to environ-
or chronic follicular and bronchial inflammation and pro- mental agents or drugs, the primary treatment is to elimi-
gressive, usually irreversible, pulmonary fibrosis, bilateral nate the factors causing the disease. If the disease has
diffuse pulmonary lesions in imaging examinations, and an autoimmune background, glucocorticoids and immu-
ventilation restrictions. Despite the differentiated etiol- nosuppressive drugs are used to reduce the inflammation
ogy, the clinical image of ILDs is similar, and results from leading to progressive fibrosis. However, in some diseases
the presence of diffuse and irreversible fibrous lesions of unknown etiology, such as IPF, there are still no effective
of the alveolar parenchyma of the lung interstitium. Spe- pharmacological methods that significantly improve surviv-
cific forms of ILDs can be differentiated from one another al. Intensive research has been carried out in the past decade
based on clinical data, radiological imaging and lung bi- to find effective antifibrotic and anti-inflammatory drugs.5
opsy. The histopathologic changes in the lungs of patients Thus ILD treatment often includes only oxygen therapy
with ILDs can range from granulomatous inflammation in case of respiratory failure. The progression of lung fibro-
without parenchymal fibrosis in patients with sarcoidosis sis depends on the underlying disease, and is particularly
to expansive pulmonary fibrosis with architectural distor- rapid in IPF. In selected patients with treatment-resistant
tion of the lung in patients with idiopathic pulmonary fi- progressive ILD, the only therapeutic method is lung
brosis (IPF). Clinical ILD features include exercise-induced transplantation. However, due to an insufficient number
dyspnea, exercise-induced hypoxemia, progressive skeletal of donors and numerous contraindications, access to this
muscle weakness, and deterioration of exercise tolerance. method is limited. Therapeutic options for ILDs are often
The main symptoms of fibrosis are progressive decreases limited, and do not guarantee improvement in the quality
in forced vital capacity (FVC) and in the diffusing capac- of life or its prolongation.5,6 An increasing number of re-
ity of the lung for carbon monoxide (DLCO). Restriction ports indicate that in most patients with ILDs, pulmonary
of pulmonary ventilation leads to respiratory failure, fur- rehabilitation (PR) is a widely accessible treatment that
ther enhanced by diminished alveolar blood flow resulting can significantly improve exercise capacity and reduce
from capillary destruction and hypoxic vasoconstriction.1 dyspnea.7
The onset of the disease is usually non-specific; patients
may complain of a low-grade fever or a fever with unclear
etiology, coughing and deteriorated exercise tolerance. Pulmonary rehabilitation
If the patient is a smoker, chronic pulmonary obstructive
disease (COPD) is usually suspected, because spirometry
principles
focusses on disorders in lung ventilation. In patients with Pulmonary rehabilitation is an evidence-based, mul-
ILD, airflow in the respiratory tract is not disturbed; ob- tidisciplinary and comprehensive medical intervention
struction is rare, except in patients with sarcoidosis.2 A di- dedicated to patients with a variety of symptoms of chronic
agnosis of ILD is sometimes based on changes in the chest diseases and reduced daily activity. The combination of PR
X-ray image, especially in patients in whom this examina- with an individualized treatment plan reduces the symp-
tion is performed periodically due to occupational expo- toms, improves physical fitness, enhancing the functional
sure. In some cases, the onset of ILD may be acute, with and psychological status and quality of life of patients with
symptoms requiring immediate medical intervention: respiratory diseases. The primary problem of patients with
pneumothorax, hemoptysis and rapid progressive respi- progressive chronic lung diseases is a gradual increase
ratory failure. Interstitial lung diseases may be associated in symptoms such as dyspnea, persistent cough, easy fatigue
with exposure to occupational and environmental factors, and weakness, which cause restrictions of daily physical
drugs (amiodarone, chemotherapy drugs, methotrexate), activity, resulting in muscle weakness and functional limi-
or be accompanied by multiple connective tissue diseases tations. The patient becomes disabled, often experiences
(systemic lupus erythematosus, rheumatoid arthritis, sys- anxiety and/or depression and gradually withdraws from
temic scleroderma, or dermatomyositis). In many cases, social life. The quality of life deteriorates considerably.
the etiology is unknown. The purposes of PR include physical capacity improve-
In a European study the prevalence of ILDs was esti- ment, reduction in disease symptoms, relief from negative
mated of 97.9/10,000. The most prevalent diagnoses were emotional states, development of a healthy lifestyle with
sarcoidosis (42.6%), connective tissue disease-associated adequate physical activity, elimination of smoking, and
ILDs (CTD-ILDs) (16%), IPF (11.6%), and occupational ILDs giving patients the ability to self-monitor their symptoms,
(5.0%). 3 The data from earlier studies also showed that the course of the disease and their compliance with recom-
the most frequent ILDs are IPF and sarcoidosis, which mended treatments. Pulmonary rehabilitation includes phys-
together comprise about 50%.4 ical examinations, chest physiotherapy, individual strength,
Adv Clin Exp Med. 2020;29(2):257–264 259

endurance and respiratory training, as well as relaxation (maximal oxygen uptake – VO2max). The obvious benefits
techniques aimed at reducing muscle tension and anxiety of PR mean that over the years, attempts have been made
and/or depression. Patients are educated about the disease, to extend PR indications to other groups of patients with
lifestyle, nutrition, and the harmfulness of smoking. chronic lung diseases.
Pulmonary rehabilitation has been used for many years
in patients with COPD, and numerous benefits have been
noted, particularly reduced dyspnea, increased effort Pulmonary rehabilitation in ILDs
tolerance and improved quality of life.7 The indications
for PR and its benefits for patients with COPD have been Although ILDs and COPD are completely different
well-defined.8 diseases, they are similar in many ways: Both diseases
According to American Thoracic Society/European involve respiratory distress, increased respiratory effort
Respiratory Society guidelines, rehabilitation should be and abnormal gas exchange, and the incidence of anxiety
performed by a multidisciplinary team of pulmonologists, and depression is higher than in the general population.
physiotherapists, psychologists, and nurses.7 The first step Numerous similarities indicate that PR in patients with
is detailed diagnostic testing that allows the PR to be ad- ILDs may produce similar beneficial effects as in those
justed to the current state of the patient, including an eval- with COPD.9 Among ILD patients, those with IPF have
uation of the patient’s quality of life, the degree of anxiety particularly poor prognoses. The median of survival since
and depression, and an evaluation of minimal exercise the diagnosis has not changed in this group in the last
tolerance. In addition, the strength of the peripheral 30 years, and it is no more than 5 years.10 Until recently,
muscles can be assessed. A six-minute walk test (6MWT) apart from oxygen therapy, there was no therapeutic
is a commonly used method of evaluating exercise toler- ­option for these patients. Because of the rapid progres-
ance. It is extremely important to evaluate O2 saturation sion of the disease, patients with IPF are rarely quali-
during exercise, and in particular the greatest decrease fied for PR. The recent introduction of 2 new medicinal
in O2 saturation during the 6MWT (nadir SPO2).8 products for IPP − pirfenidone and the tyrosine kinase
Pulmonary rehabilitation includes both education and inhibitor nintedanib − may improve this situation. Early
supervised exercise. The scope of the education should in- addition of PR to pharmacotherapy can improve the pa-
clude an explanation of the pathomechanisms of the dis- tients’ survival.6
ease, an explanation of the appropriate treatment, breathing No guidelines concerning the optimization of exercise
techniques, principles of healthy nutrition, indications for for patients with ILDs have been developed yet. Random-
air travel in patients with respiratory failure, the correct use ized trials have included all interstitial disorders or have
of inhalers, and dealing with stress. Physical exercises in- been dedicated to a defined subgroup, such as patients
clude individually modified endurance and aerobic training. with IPF.11,12 The results of PR results are highly affected
The main problems hindering the widespread use of PR by the diagnosis. This especially applies to IPF patients,
are limited funding from healthcare systems despite in- who show less improvement in physical performance af-
creasing awareness of the benefits of PR, a lack of knowl- ter PR compared to patients with other ILDs. However,
edge among physicians and a shortage of experienced re- the faster course of IPF compared to most ILDs should be
habilitators. Pulmonary rehabilitation should be standard taken into account.13
care in patients with COPD, along with pharmacotherapy, The basic parameter for PR performance evaluation
oxygen therapy and non-invasive ventilation. is the change in minimal important difference (MID)
Pulmonary rehabilitation favorably modifies the course in the 6MWT. The MID has been set at 54 m in people
of COPD in many ways, causing: with COPD, although there are opinions that this value
1. reduced number of hospitalizations, is exaggerated.14 For patients with ILDs, the MID value has
2. increased exercise tolerance, not been established; the range varies from 24 m to 45 m,
3. reduced dyspnea, depending on the statistical method chosen.15,16 The se-
4. increased resistance and muscle strength, verity of symptoms, mainly dyspnea, is also evaluated.
5. improved quality of life, The Borg Dyspnea Scale and the Medical Research Coun-
6. reduced emotional disorders, cil’s (MRC) Baseline Dyspnea Index (BDI) and Transition
7. increased self-reliance, Dyspnea Index (TDI) are used to evaluate the severity
8. increased fat-free body mass, of dyspnea. Cough, depression, anxiety, and fatigue may
9. increased breath volume and oxygen saturation, and also be evaluated. For the health-related quality of life
10. improved capacity of the skeletal muscles at the cel- evaluation, the most commonly used questionnaires are
lular level.7 the Short Form Health Survey (SF-36), the Chronic Respi-
From a clinical point of view, the exercise component ratory Disease Questionnaire (CRDQ) and St. George’s
of PR increases the patient’s physical capacity, which Respiratory Questionnaire (SGRQ).17,18 An additional pa-
is the most often measured by the 6MWT or oxygen up- rameter is pulse oximetry during exercise to determine
take during a maximal cardiopulmonary exercise test nadir SpO2 during the 6MWT.19
260 K. Wytrychowski et al. Rehabilitation in interstitial lung diseases

The number of controlled PR studies in ILDs is small, but chronotropic response of the heart to exercise and pro-
a systematic increase is noticeable. A meta-analysis pub- longed tachycardia are often observed, which may indi-
lished in 2014 included a total of 8 papers concerning PR cate cardiac sarcoidosis. In some patients, an excessively
in patients with ILDs. No side effects were observed in any fast resting heart rate may limit exercise capacity, since
of the studies. The weighted mean difference in the dis- the heart rate prevents the patients from continuing ex-
tance in the 6MWT was 44.34 m. Statistically significant ercise shortly after they begin. In this situation, the use
reductions in dyspnea was observed in all the studies. Im- of drugs with negative chronotropic effects can be ben-
proved quality of life was identified using various ques- eficial in terms of the results of rehabilitation. However,
tionnaires. The improvement directly after PR that was the implementation of this kind of therapy in the popula-
observed in the subpopulation of IPF patients was similar tion with pulmonary pathologies has numerous limitations,
to that of the whole population examined. The limitation including the small group of available drugs. On the one
was the small number of study groups (in total, 86 patients hand, some of them, such as ivabradine, have not been
underwent PR and 82 comprised the control groups).20 tested in these patients; and on the other, β-blockers may
In a meta-analysis of 142 patients with IPF published have a potentially adverse effect. Nebivolol, a β1-selective
in 2018, 4 studies evaluated the short-term benefits of PR. agent, is preferred in these patients because it causes quite
Significant improvement was found in the 6MWT, along low negative chronotropic effects at the standard dose
with a significant decrease in the total SGRQ score.21 used in hypertension compared to other representatives
In a large study including 402 patients on a widespread of the class. Another common problem is the coexistence
ILD spectrum, PR was performed at a specialist center for of left ventricular diastolic dysfunction in many patients.
an average of 30 days with 5 sessions per week. Clinically In this situation, a lack of proper heart rate control impairs
significant improvements in the patients’ quality of life, exercise tolerance, thus significantly affecting training
physical capacity (the mean increase compared to the base- opportunities.
line 6MWT was 46 m) and a slight improvement in FVC Worsening tolerance to exercise may also be caused
(+1%) were observed. The only predictor of a significant by skeletal muscle dysfunction. The mechanisms
response to PR was a low baseline 6MWT; the largest in- of this phenomenon include changes in skeletal muscles
crease in the distance was observed in this group. Low in the course of an underlying disease (e.g., dermatomyosi-
6MWT scores occurred in patients with low FVC, low tis); myopathy induced by chronic systemic steroid therapy;
total lung capacity (TLC) and treated with home oxygen and progressive immobilization of the patient.22
therapy. In this study, conducted in an inpatient setting, A progressive decrease in the 6MWT is a predictor of in-
80% of the patients were on home oxygen therapy. This creased mortality, especially in IPF patients, among whom
is further evidence of the value of PR use in patients with a drop in the 6MWT by more than 61 m in 6 months and
advanced respiratory failure.22 desaturation below 88% during exercise are associated with
Different parameters are evaluated in different publica- increased mortality.8
tions. The manner in which PR is performed (outpatient The course and prognosis of ILDs is affected not only
or inpatient) also varies from study to study; the study by the primary disease, but also by accompanying ones.
groups include patients with assorted ILDs or only 1 dis- Exercise tolerance in ILD patients is mainly affected
ease, e.g., IPF, and the duration of PR varies. However, by cardiovascular and metabolic diseases and smoking.23
despite the lack of detailed guidelines, PR is becoming Accompanying diseases are divided into pulmonary and
an increasingly common component of multidisciplinary extrapulmonary ones. Pulmonary fibrosis enhances the ex-
care for people with ILDs. pression of cytokines and growth factors, promoting the de-
It is currently believed that patients with ILDs should velopment of atherothrombosis through an increase in sys-
be included in PR programs typically lasting 8 weeks, with temic inflammation and hypercoagulability. This leads
at least 2 weekly sessions of at least 30 min of aerobic train- to a two-fold increase in the risk of ischemic heart disease
ing. Spirometry tests play a lesser role in qualifying ILD (IHD) compared to the general population. The coexis-
patients for PR than in case of COPD, because a small tence of pulmonary fibrosis and IHD significantly shortens
degree of dysfunction in lung function tests is often ob- the patients’ survival time.20 Among IPF patients, as many
served in patients with significant limitations to exercise as 1/3 have recognized IHD. The risk of venous thrombo-
tolerance. The mechanism of exercise dyspnea in ILDs embolism is more than three-fold higher in the population
is complex. The primary role is played by dysfunction of patients with ILDs compared to the general population.
of the alveolar–capillary barrier associated with thicken- This requires early implementation of antithrombotic pro-
ing of the pulmonary artery walls. Developing pulmo- phylaxis during hospitalization.24
nary hypertension is a result of chronic hypoxia-induced Pulmonary arterial hypertension (PAH), defined as mean
vasoconstriction and thromboembolic changes leading pulmonary arterial pressure ≥25 mm Hg evaluated dur-
to the destruction of blood vessels. There is a strong cor- ing right heart catheterization, may occur in any c­ hronic
relation between increases in pulmonary pressure and lung disease. This also applies to patients with ILDs,
decreases in exercise tolerance. In addition, an impaired among whom the risk of PAH depends on the diagnosis.
Adv Clin Exp Med. 2020;29(2):257–264 261

It is generally accepted that the more severe the course disease separately. A classic example is the coexistence
of the disease is, the higher the incidence of PAH. For of emphysema and ILDs. In 2005, Cottin et al. described
example, PAH is more common in patients with IPF a syndrome of coexistence of upper lobe emphysema and
than in cases of sarcoidosis. A diagnosis of PAH results fibrosis of the lower lung lobes. 31 The incidence of emphy-
in rapid deterioration of physical performance, the need sema in ILD cases is estimated at 10%, and primarily con-
for home oxygen therapy and increased mortality. Trans- cerns smoking males, who are more likely to develop lung
thoracic echocardiography and right heart catheteriza- cancer and PAH. The frequency of home oxygen therapy
tion are routinely used in the diagnostics. The simple test is increased in this group. An increase in the incidence
is the 6MWT, which reveals an impaired normalization of lung cancer is observed in patients with IPF, systemic
of the heart rate after exercise: A heart rate difference im- sclerosis, dermatomyositis, ascites, and asbestosis.24
mediately after exercise and after 1 min rest that is lower The currently available literature presents 2 different
than 13 bpm suggests PAH.25 Special attention is required opinions on responses to PR. Some authors estimate that
in case of patients with PAH in the phase of right-sided greater improvement is observed in patients whose base-
heart failure. The presence of clinically prominent PAH line FVC is higher and whose desaturation after exercise
leads to recommendations for limiting intense exercise, is lower. These authors conclude that it is crucial to in-
with the fear that exercise-induced rapid pulmonary hy- troduce PR as early as possible in this group of patients.29
pertension with the symptoms of right ventricular cir- Other authors observe that lower 6MWT baseline values
culatory failure may lead to sudden death.26 Pulmonary result in the greatest increase after PR, suggesting that even
arterial hypertension patients are at an increased risk of PR in very advanced disease respiratory rehabilitation makes
complications, including arrhythmias, syncope and dizzi- sense.32 It seems that both opinions are correct, proving
ness, which may occur in 13% of patients.26,27 that improvements in ILD patients can be achieved in a va-
Physical exercise is associated with sympathetic activa- riety of diseases with a broad spectrum of progression.33
tion, which increases the risk of arrhythmias. At the same The improvement in ILDs patients after PR persists for
time, the population of patients with respiratory diseases up to 6 months, although detailed evaluations are affected
is thought to have hypoxia-related arrhythmias. In the light by the high percentage of patients who do not complete
of some research, this is not a significant impediment rehabilitation programs, indicated as 28% by Ryerson
to physical activity. Although the majority of patients had et al. 34 In a group of 36 patients with ILDs of varying eti-
24-hour asymptomatic single premature supraventricular ology, 16 underwent a 6-month PR program, comprising
and ventricular beats, no significant arrhythmia was ob- a total of 60 sessions, and control tests were carried out
served during the 6MWT despite a significant decrease 1 year after the conclusion. It turned out that improvement
in SpO2.27 in lung function and exercise tolerance are visible even
The risk of complications during PR decreases when 6 months after finishing a program of this kind. Signifi-
interval training with a maximum heart rate increase up cant differences between the PR group and the control
to 120 bpm and a combination of endurance and strength group were observed after a year, evaluating the 6MWT,
exercises is used.28 muscle strength and maximal workload on a cycle er-
Gastroesophageal reflux disease (GERD) is a very com- gometer. 35 In a group of 48 IPF patients qualified for lung
mon extrapulmonary comorbidity. In patients with IPF, transplantation, 12 weeks of PR were conducted. The pa-
the incidence is up to 80%, and symptoms may persist tients were characterized by severe lung function impair-
despite the use of proton pump inhibitors.25 Sleep apnea ment (average FVC was 49% ±13% of the predicted value
syndrome occurs in more than half of the patients. Pre- and DLCO was 46% ±17%). The improvement was assessed
dictors are a high body mass index (BMI) and deterio- on the basis of the 6MWT and the SF-36 questionnaire.
rating lung function.24 Depression, diagnosed in approx. Out of this group, 31 participants successfully completed
25% of patients with ILDs, especially in the group with the PR, and the rest of the respondents did not show any
severe dyspnea, sleep disorders, markedly reduced FVC significant differences in the parameters assessed before
and many associated conditions, is related to a progressive the start of PR. 36
reduction in physical activity.29 Depression is an indepen- In a meta-analysis of 9 PR programs for ILD patients,
dent risk factor, and regular screening for its occurrence 8 programs were on an outpatient basis. The average dura-
is recommended.30 tion was 10 weeks, with 2 sessions per week. Pulmonary
rehabilitation complications are rare, mainly involving
exercise-induced hypoxemia, ILD-specific symptoms and
Pulmonary diseases arrhythmias. Most authors recommend interrupting ex-
ercise when O2 saturation drops below 80%. Continuing
accompanying ILDs the exercise in such patients requires oxygen supplementa-
Each pulmonary disease accompanying ILDs results tion to achieve saturation above 85% and even up as high
in an additive effect, causing greater lung function as 90%.37 Oxygen supplementation during PR in patients
­abnormalities and increased mortality compared to each with ILDs improves exercise tolerance.38
262 K. Wytrychowski et al. Rehabilitation in interstitial lung diseases

General rules of qualification for (r = 0.78) with maximal oxygen uptake in the ergospiro­
metry exercise test. The minimum significant difference
pulmonary rehabilitation in ILDs (MCID) in the 6MWT has been determined as 28 m.15
Patients with a broad spectrum of ILDs are qualified In another study, based on a study population 822 patients
for PR, most commonly with IPF, sarcoidosis and post- with IPF the estimated MCID was 24–45 m.16 The total dis-
inflammatory pulmonary fibrosis. The qualification pro- tance in the 6MWT provides an easy evaluation of physical
cedure should include: capacity. The 6MWT score increases with the reduction
1. a detailed interview; of fatigue observed after aerobic training.40 A gradual de-
2. a physical examination in which attention should be cline in the 6MWT is associated with increased mortality
paid to the presence of musculoskeletal disorders that may in ILD patients, especially those with IPF.41 A meta-anal-
significantly impair the patient’s physical activity; ysis of studies performed on small groups of patients (43
3. cardiac diagnostics, including an evaluation of isch- in total who underwent PR and 42 controls) showed that
emic changes, arrhythmias and cardiac conduction (espe- the patients with IPF demonstrated less improvement after
cially in patients with sarcoidosis) as well as pulmonary PR than the patients with other ILDs. In the IPF group,
pressure; an average increase in the 6MWT immediately after PR
4. cardiac safety parameters, including a pulse rate was 26.55 m; in the remaining patients with ILDs, it was
at rest <120 bpm, right ventricular systolic blood pressure 38.61 m. This may be related to the initial severity and
(RVSBP) <40 mm Hg, ejection fraction ≥40%, and no recent faster course of the disease in IPF patients.41 In a study
ischemic lesions visible on electrocardiography (ECG); conducted on a group of 32 patients with IPF, 15 were sub-
5. elimination of harmful environmental factors like jected to a 12-week exercise-based PR program and showed
smoking and exposure to allergens; significant improvement in exercise tolerance, functional
6. a diagnosis of accompanying diseases; capacity and FVC. To evaluate exercise tolerance, the car-
7. an evaluation of peripheral muscle strength; diopulmonary exercise test was used; after 12 weeks of PR,
8. the ability to live independently. there was a significant increase in VO2max. This is an in-
Pulmonary rehabilitation should be introduced as early teresting observation, because in patients with other lung
as possible, especially for IPF patients. The basic safety diseases, e.g., COPD, there is no improvement in VO2max
parameter is a stable course of the disease. In CTD-ILDs and FVC after PR. Considering that the average survival
(rheumatoid arthritis, systemic scleroderma), pain and time of IPF patients is 3–5 years from diagnosis, improve-
stiffness of the joints can be a problem. ment in these parameters in a group of IPF patients an av-
Contraindications to PR include: erage of 2–3 years following their diagnosis shows that
1. an unstable course of the disease; even in such a rapidly progressing disease, PR can cause
2. fainting after effort during an examination; measurable improvement.42 Quality of life questionnaires
3. symptoms of right ventricular cardiovascular failure; and nadir SpO2 are simple and credible ways to evaluate
4. an uncontrolled course of accompanying diseases; the patients’ response to PR.32
and The effectiveness of PR in patients with ILD is assessed
5. any disease that prevents exercise training.20 differently in different publications. Differences are caused
Despite many uncertainties, the current state of knowl- by:
edge allows PR to be included in standard care in ILD 1. different patient groups (usually there are better re-
patients in 6–12-month intervals.38 Due to the different sults in ILD groups with mixed etiology);
etiology and prognoses of ILDs, the effects of PR will 2. different patient conditions (in patients with IPF,
largely depend on the diagnosis. Especially in diseases short-term study results are less affected by the rapid dis-
with an acute onset, it is advisable to achieve remission ease progression);
or stabilize the disease before starting PR. In IPF, due 3. different PR programs, lasting 12–24 weeks, with
to the rapid progression of the disease, early qualification varied intensity (usually 2–3 times a week); and
for PR is recommended. The positive effects of PR can last 4. varied parameters assessing the effectiveness of PR:
up to 6 months.32,39 exercise tolerance, functional capacity, pulmonary func-
Numerous parameters are used to evaluate the effective- tion tests, muscle strength, and health-related quality
ness of PR in ILDs: of life.
1. changes in the distance in 6MWT;
2. lowest O2 saturation value in the 6MWT test (nadir
SpO2 less exercise-induced oxyhemoglobin desaturation); Conclusions
3. resting RSVBP; and
4. scores on specific lung disease questionnaires (SGRQ, Pulmonary rehabilitation is an important part of com-
CRDQ and MRC-BDI). prehensive care for patients with ILDs. The principles of re-
The 6MWT in patients with IPF is highly repeatable habilitation in this group of patients do not differ from
at short intervals (1–2 weeks) and highly correlated the standards of PR for patients with COPD; the major
Adv Clin Exp Med. 2020;29(2):257–264 263

differences are due to poorer exercise tolerance and faster 15. ATS Committee on Proficiency Standards for Clinical Pulmonary Func-
tion Laboratories. ATS Statement: Guidelines for the Six-Minute Walk
development of respiratory failure in patients with ILDs.
Test. Am J Respir Crit Care Med. 2002;166(1):111–117.
Exercise-induced desaturation is frequently observed dur- 16. du Bois RM, Weycker D, Albera C, et al. Six-minute-walk test in idio-
ing PR. This is the main source of complications in patients pathic pulmonary fibrosis: Test validation and minimal clinically
with ILDs, and it occurs more frequently than in COPD important difference. Am J Respir Crit Care Med. 2011;183(9):1231–1237.
17. Holland AE, Hill CJ, Conron M, Munro P, McDonald CF. Small changes
patients. Pulmonary rehabilitation centers for ILD patients in six-minute walk distance are important in diffuse parenchymal
should be equipped with an oxygen source, a resuscitation lung disease. Respir Med. 2009;103(10):1430–1435.
kit, a defibrillator, and experienced staff. Early qualifi- 18. Bajwah S, Ross JR, Peacock JL, et al. Interventions to improve symp-
toms and quality of life of patients with fibrotic interstitial lung dis-
cation and stabilization of the progression of ILDs and ease: A systematic review of the literature. Thorax. 2013;68(9):867–879.
any accompanying diseases can reduce the risk of com- 19. Swigris JJ, Fairclough DL, Morrison M. Benefits of pulmonary reha-
plications and achieve visible improvement in the patient’s bilitation in idiopathic pulmonary fibrosis. Respir Care. 2011;56(6):
783–789.
health status. 20. Dowman L, Hill CJ, Holland AE. Pulmonary rehabilitation for inter-
stitial lung disease. Cochrane Database Syst Rev. 2014;10:CD006322.
ORCID iDs 21. Gomes-Neto M, Silva CM, Ezequiel D, Conceição CS, Saquetto M,
Krzysztof Wytrychowski  https://orcid.org/0000-0003-4457-1027 Machado AS. Impact of pulmonary rehabilitation on exercise toler-
Anna Hans-Wytrychowska  https://orcid.org/0000-0003-4842-5262 ance and quality of life in patients with idiopathic pulmonary fibrosis:
Paweł Piesiak  https://orcid.org/0000-0002-3166-1456 A systematic review and meta-analysis. J Cardiopulm Rehabil Prev.
Marta Majewska-Pulsakowska  https://orcid.org/0000-0001-6575-0521 2018;38(5):273–278.
Krystyna Rożek-Piechura  https://orcid.org/0000-0001-5589-4978 22. Huppmann P, Szczepanski B, Boensch M, et al. Effects of inpatient
pulmonary rehabilitation in patients with interstitial lung disease.
Eur Respir J. 2013;42(2):444–453.
References 23. Flaherty KR, Andrei AC, Murray S, et al. Idiopathic pulmonary fibro-
1. Wiatr E. Definicja i klasyfikacje chorób śródmiąższowych płuc. In: sis: Prognostic value of changes in physiology and six-minute-walk
Wiatr E, Rowińska-Zakrzewska E, Pirożyński M, eds. Choroby śród­ test. Am J Respir Crit Care Med. 2006;174(7):803–809.
miąższowe płuc. Bielsko-Biała, Poland: Alfa Medica Press; 2012:15–20. 24. Kizer JR, Zisman DA, Blumenthal NP, et al. Association between pul-
2. Boros P. Zaburzenia czynnościowe w chorobach śródmiąższowych monary fibrosis and coronary artery disease. Arch Intern Med. 2004;
płuc. In: Wiatr E, Rowińska-Zakrzewska E, Pirożyński M, eds. Choroby 164(5):551–556.
śródmiąższowe płuc. Bielsko-Biała, Poland: Alfa Medica Press; 2012: 25. King C, Nathan SD. Identification and treatment of comorbidities
48–61. in idiopathic pulmonary fibrosis and other fibrotic lung diseases.
3. Duchemann B, Annesi-Maesano I, Jacobe de Naurois C, et al. Prev- Curr Opin Pulm Med. 2013;19(5):466–473.
alence and incidence of interstitial lung diseases in a multi-ethnic 26. Sherner J, Collen J, King CS, Nathan SD. Pulmonary hypertension
county of Greater Paris. Eur Respir J. 2017;50(2). pii: 1602419. doi:10. in idiopathic pulmonary fibrosis: Epidemiology, diagnosis and ther-
1183/13993003.02419-2016 apeutic implications. Curr Respir Care Rep. 2012;1(4):233–242.
4. Interstitial Lung Diseases – ERS. https://www.erswhitebook.org/ 27. Mereles D, Ehlken N, Kreuscher S, et al. Exercise and respiratory train-
chapters/interstitial-lung-diseases/. ing improve exercise capacity and quality of life in patients with
5. Meyer KC. Diagnosis and management of interstitial lung disease. severe chronic pulmonary hypertension. Circulation. 2006;114(14):
Transl Respir Med. 2014;2:4. doi:10.1186/2213-0802-2-4 1482–1489.
6. Loveman E, Copley VR, Colquitt J, et al. The clinical effectiveness and 28. de Man FS, Handoko ML, Groepenhoff H, et al. Effects of exercise
cost-effectiveness of treatments for idiopathic pulmonary fibrosis: training in patients with idiopathic pulmonary arterial hyperten-
A systematic review and economic evaluation. Health Technol Assess. sion. Eur Respir J. 2009;34(3):669–675.
2015;19(20):i–xxiv,1–336. 29. Fox BD, Kassirer M, Weiss I, et al. Ambulatory rehabilitation improves
7. Nici L, Donner C, Wouters E, et al; ATS/ERS Pulmonary Rehabilitation exercise capacity in patients with pulmonary hypertension. J Card
Writing Committee. American Thoracic Society/European Respira- Fail. 2011;17(3):196–200.
tory Society Statement on Pulmonary Rehabilitation. Am J Respir Crit 30. Holland AE, Fiore JF Jr, Bell EC, et al. Dyspnoea and comorbidity con-
Care Med. 2006;173(12):1390–1413. tribute to anxiety and depression in interstitial lung disease. Respiro­
8. Spruit MA, Singh SJ, Garvey C, et al; ATS/ERS Task Force on Pulmo- logy. 2014;19(8):1215–1221.
nary Rehabilitation. An Official American Thoracic Society/European 31. Cottin V, Nunes H, Brillet P-Y, Delaval P. Combined pulmonary fibro-
Respiratory Society Statement: Key Concepts and Advances in Pulmo- sis and emphysema: A distinct underrecognised entity. Eur Respir J.
nary Rehabilitation. Am J Respir Crit Care Med. 2013;188(8):1011–1027. 2005;26(4):586–593.
9. Rochester CL, Vogiatzis I, Holland AE, et al; ATS/ERS Task Force on Pol- 32. Holland AE, Hill CJ, Glaspole I, Goh N, Mc-Donald CF. Predictors of
icy in Pulmonary Rehabilitation. An Official American Thoracic Soci- benefit following pulmonary rehabilitation for interstitial lung dis-
ety/European Respiratory Society Policy Statement: Enhancing Imple- ease. Respir Med. 2012;106(3):429–435.
mentation, Use, and Delivery of Pulmonary Rehabilitation. Am J Respir 33. Deniz S, Şahin H, Yalnız E. Does the severity of interstitial lung dis-
Crit Care Med. 2015;192(11):1373–1386. ease affect the gains from pulmonary rehabilitation? Clin Respir J.
10. Swigris JJ, Brown KK, Make BJ, Wamboldt FS. Pulmonary rehabilita- 2018;12(6):2141–2150.
tion in idiopathic pulmonary fibrosis: A call for continued investiga- 34. Ryerson CJ, Cayou C, Topp F, et al. Pulmonary rehabilitation improves
tion. Respir Med. 2008;102(12):1675–1680. long-term outcomes in interstitial lung disease: A prospective cohort
11. Flaherty KR, Thwaite E, Kazerooni EA, et al. Radiological versus his- study. Respir Med. 2014;108(1):203–210.
tological diagnosis in UIP and NSIP: Survival implications. Thorax. 35. Perez-Bogerd S, Wuyts W, Barbier V, et al. Short and long-term effects
2003;58(2):143–148. of pulmonary rehabilitation in interstitial lung diseases: A randomised
12. Holland AE, Hill CJ, Conron M, Munro P, McDonald CF. Short term controlled trial. Respir Res. 2018;19(1):182.
improvement in exercise capacity and symptoms following exer- 36. da Fontoura FF, Berton DC, Watte G, et al. Pulmonary rehabilitation
cise training in interstitial lung disease. Thorax. 2008;63(6):549–554. in patients with advanced idiopathic pulmonary fibrosis referred
13. Nishiyama O, Kondoh Y, Kimura T, et al. Effects of pulmonary reha- for lung transplantation. J Cardiopulm Rehabil Prev. 2018;38(2):
bilitation in patients with idiopathic pulmonary fibrosis. Respirology. 131–134.
2008;13(3):394–399. 37. Nishiyama O, Kondoh Y, Kimura T, et al. Effects of pulmonary reha-
14. Holland A, Hill C. Physical training for interstitial lung disease. Cochrane bilitation in patients with idiopathic pulmonary fibrosis. Respirology.
Database Syst Rev. 2008;4:CD006322. 2008;13(3):394–399.
264 K. Wytrychowski et al. Rehabilitation in interstitial lung diseases

38. Leach RM, Davidson AC, Chinn S, Twort CH, Cameron IR, Bateman NT. 41. Keyser RE, Christensen EJ, Chin LM, Woolstenhulme JG. Changes
Portable liquid oxygen and exercise ability in severe respiratory dis- in fatigability following intense aerobic exercise training in patients
ability. Thorax. 1992;47(10):781–789. with interstitial lung disease. Respir Med. 2015;109(4):517–525.
39. Raghu G, Collard HR, Egan JJ, et al; ATS/ERS/JRS/ALAT Committee 42. Vainshelboim B, Myers J, Oliveira J, Izhakian S, Unterman A, Kramer MR.
on Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Physiological responses and prognostic value of common exer-
Statement. Idiopathic Pulmonary Fibrosis: Evidence-Based Guide- cise testing modalities in idiopathic pulmonary fibrosis. J Cardio­
lines for Diagnosis and Management. Am J Respir Crit Care Med. 2011; pulm Rehabil Prev. 2018 Sep 24 [Epub ahead of print]. doi:10.1097/
183(6):788–824. HCR.0000000000000362
40. Ferreira A, Garvey C, Connors GL, et al. Pulmonary rehabilitation
in interstitial lung disease: Benefits and predictors of response. Chest.
2009;135(2):442–447.