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Table of Contents
REVIEW ARTICLE
Year : 2021  |  Volume : 4  |  Issue : 1  |  Page : 6-11

Cardiopulmonary exercise testing in the clinical evaluation of patients with interstitial lung disease: A systematic review


Department of Medicine, King Saud University, Riyadh, Saudi Arabia

Date of Submission04-May-2020
Date of Decision01-Jun-2020
Date of Acceptance15-Jun-2020
Date of Web Publication09-Dec-2020

Correspondence Address:
Abdullah Rashed Alharbi
Department of Medicine, King Saud University, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2589-627X.303905

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  Abstract 


Interstitial lung diseases involve multiple pathological mechanisms, including interstitial and alveolar destruction. In addition, pulmonary inflammation associated with the disease can reduce lung capacity and induce hypoxia, which becomes more significant with exercise. Cardiopulmonary exercise testing is used for diagnostic purposes and functional evaluation. This type of testing can measure the walking distance versus time to estimate the functional capacity of patients enrolled in rehabilitation programs. It can also assess cardiopulmonary functions in terms of carbon dioxide output, pulmonary gas exchange, as well as lung response influenced by exercise. Therefore, this systematic review aims to explore the clinical significance of using cardiopulmonary exercise testing in interstitial lung disease by reviewing the present medical literature. The literature review was carried out through Medline, Ovid, PubMed, and Google scholar databases, between 2010 and 2020. Searching terms included were a combination of “Cardiopulmonary exercise testing” AND “interstitial lung diseases.” After literature review, results were revised manually to include only original research articles evaluating the use of cardiopulmonary testing in interstitial lung disease. Selected trials mentioned the respiratory parameters evaluated. Seven articles were eligible for inclusion in this systematic review. The available data on cardiopulmonary exercise testing in interstitial lung diseases are explicitly still unclear. This finding opens the gates for future well-designed studies on this population.

Keywords: Cardiopulmonary, exercise testing, gas exchange, interstitial lung diseases


How to cite this article:
Alharbi AR. Cardiopulmonary exercise testing in the clinical evaluation of patients with interstitial lung disease: A systematic review. J Nat Sci Med 2021;4:6-11

How to cite this URL:
Alharbi AR. Cardiopulmonary exercise testing in the clinical evaluation of patients with interstitial lung disease: A systematic review. J Nat Sci Med [serial online] 2021 [cited 2021 Jan 27];4:6-11. Available from: https://www.jnsmonline.org/text.asp?2021/4/1/6/303905




  Introduction Top


Interstitial lung diseases constitute a group of different diseases that can lead to fibrosis and destruction of pulmonary parenchyma.[1] Exercise intolerance is a primary manifestation in patients with interstitial lung diseases.[2] The decrease exercising ability is usually correlated to significant dyspnea, especially with effort, in addition to fatigue, increased morbidity and reduced quality of life.[3]

Reduced pulmonary function during exercise could be used as a prognostic marker for mortality due to reduced oxygen capacity, and progressing exercise-induced hypoxemia.[4] However, the exact mechanism for reduced exercise capacity is still unclear[5] though it is mainly associated with abnormal gas exchange and impaired mechanical ventilatory capacity.[6]

Interstitial lung diseases can lead to a reduced inhalational capacity as well as abnormal gas-exchange.[7] Impairment of gas-exchange is best identified using a ratio between destructed pulmonary area and tidal volume and partial oxygen pressure.[8] These indicators can be used as early markers for abnormalities associated with the chronic condition of interstitial lung diseases.[9]

Other secondary mechanisms have been identified in interstitial lung diseases related to gas exchange pulmonary circulation, in addition to the efficiency of breathing capacity.[10] Cardiopulmonary exercise testing can show cardiovascular affection by interstitial lung diseases rather than offering mechanical respiratory restrictions.[11]

In patients with progressive interstitial lung diseases, exercise-induced hypoxemia is usually detected, leading to restriction to exercises and limitation for the quality of life of the patients.[12] Cardiopulmonary exercise testing can offer a prognostic assumption in this condition, through the detection of arterial hypoxemia and peak oxygen uptake.[13]

Currently, cardiopulmonary exercise testing is commonly used for the diagnosis of dyspnea, evaluating gas exchange and the effect of exercise on pulmonary function.[14] However, the use of cardiopulmonary exercise testing is increasing due to its availability and ease of use.[15]

Therefore, the goal of the present systematic review is to review the medical literature in the past 10 years for the clinical role of cardiopulmonary respiratory exercise test in patients with interstitial lung disease. In this review, we will explain the initial searching strategy and the selection of the included studies, followed by the methods of assessment and evaluation for the eligible studies. Then, we will explain the findings and correlations that were extracted from the included studies, followed by a thorough discussion for the most important conclusions that can be drawn from these studies.


  Methodology Top


This systematic review of the medical literature was performed per the PRISMA checklist guidelines for systematic reviews and meta-analysis. This systematic review was carried out by examining electronic databases and manual filtration of the produced results. To include eligible articles between 2010 and 2020 in the largest four databases, including Medline, PubMed, Ovid, and Google Scholar.

Search strategy

Searching terms included “cardiopulmonary exercise” AND “Interstitial lung diseases.” All the titles, in addition to abstracts that appeared from this search, were reviewed thoroughly to avoid missing any potential clinical investigations. The results were then screened to include only original research articles assessing the role of cardiopulmonary exercise testing in patients with interstitial lung disease.

Furthermore, the chosen trials mentioned the type of respiratory parameters that are evaluated using cardiopulmonary exercise testing. Moreover, all clinical investigations from different countries were included. However, only clinical studies that are published in the English language were categorized as potential articles, which can be further assessed in the second step.

Eligibility criteria

After the stage of the initial literature search, the inclusion criteria to choose the clinical investigations that will be included in the present systematic review were decided. Abstracts were manually evaluated to select the potential abstracts for further consideration. The inclusion criteria were mentioning enough data on the type of respiratory parameters that are evaluated using cardiopulmonary exercise testing. Furthermore, only studies, including adult patients with interstitial lung diseases, were included. Furthermore, references to the chosen articles were examined to define any related trials. The final stage included gathering the required data sets from the final list of eligible studies and summarized.

Trials were excluded if they were in vitro or animal studies, with overlapped or missing data, and if full-text articles are not available or studies with inappropriate study design. Full details on the search strategy are shown in [Figure 1].
Figure 1: Description of search strategy

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Data review and analysis

The first step included a primary review; a predesigned excel sheet was used for data extraction. Selected data from eligible studies were then examined through the excel sheet. Any studies that were published by one research group that evaluated similar variables were reviewed for any potential duplication. Cochrane quality-assessment tool was also used to assess the quality of the included trials.

Data were then statistically analyzed in the form of frequencies (number of cases) and valid percentages for categorical variables. Mean, standard deviations, Medians, and interquartile ratios were used to describe the numerical variable. All statistical calculations were performed by IBM SPSS (Statistical Package for the Social Science; IBM Corp, Armonk, NY, USA) release 26 for Microsoft Windows.

Before conducting any study-related procedures, institutional approval was obtained. The study was waived from using an informed consent form as the study is not involving any interventions on patients.


  Results Top


After searching the abstracts and evaluating the eligibility criteria in the identified abstracts, a total of seven articles were considered eligible to be included in this systematic review that was published between 2010 and 2020, covering a total of 340 patients who had interstitial lung diseases.

Out of the seven studies, five studies[16],[17],[18] had a prospective study design, of which, two studies had a randomized controlled design,[18],[19] one had a cross over design,[20] and one study had a cohort design.[17] Only two studies were retrospective.[16],[21]

The pulmonary parameters assessed by cardiopulmonary exercise testing have been evaluated in all studies, including oxygen uptake,[17],[18],[20],[22] arterial oxygen saturation,[18] mean pulmonary artery pressure,[19] carbon dioxide formation[16],[20] and expiration,[21] and end-tidal carbon dioxide pressure.[16]

Furthermore, four studies compared the use of cardiopulmonary exercise testing to 6-min walk test.[22],[16],[20],[18] In addition, four studies compared findings in patients with interstitial lung disease with pulmonary artery hypertension, versus patients who have normal pulmonary artery pressure.[18],[21] These comparisons have showed a better ventilatory responses and decreased oxygen saturation for cardiopulmonary exercise testing,[22] while one study[20] demonstrated that cardiopulmonary exercise testing had a significantly lower ventilation peak, carbon dioxide production, and higher peak oxygen uptake, especially in advanced stages of the disease.

In addition, the presence of pulmonary artery hypertension with interstitial lung fibrosis have been evaluated, where two study[19],[16] illustrated that cardiopulmonary exercise testing abnormalities can be linked to pulmonary artery hypertension, and it can identify different severity levels through the ratio of minute ventilation to rate of carbon dioxide production and end-tidal carbon dioxide partial pressure. Another study[21] showed that cardiopulmonary exercise testing can differentiate between patients with and without pulmonary artery hypertension in patients with interstitial lung fibrosis.

According to extracted results, all the trials considered the use of cardiopulmonary exercise testing in patients with interstitial lung disease. The included trials are discussed in detail in [Table 1].
Table 1: Eligible studies

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  Discussion Top


Patients with interstitial lung diseases have increased morbidity due to exercise intolerance and dyspnea, even with minimal effort.[23] These symptoms are attributed to the destructed alveoli and pulmonary inflammation.[24] Exercise testing, such as cardiopulmonary exercise testing and 6-min walk testing, can guide clinicians to identify the exercise capacity and prognosis of the disease.[25] However, data on the role of cardiopulmonary exercise testing in interstitial lung disease are ambiguous.[26]

This systematic review aims to examine the medical literature to identify the clinical significance of using cardiopulmonary exercise testing in patients with interstitial lung diseases. Seven studies[16],[17],[18],[19],[20],[21],[22] were considered eligible for inclusion in this review.

The clinical use of cardiopulmonary exercise testing have been evaluated in terms of the evaluation of some functional pulmonary parameters, including oxygen uptake,[17],[18],[20],[22] arterial oxygen saturation,[18] mean pulmonary artery pressure,[19] carbon dioxide formation[16],[20] and expiration,[21] and end-tidal carbon dioxide pressure.[16]

Moreover, cardiopulmonary exercise testing was compared in different clinical settings versus the significance of the 6-min walk test. Chéhère et al.[22] compared the two tests in patients with interstitial lung diseases in terms of cardiorespiratory responses. Chéhère et al.[22] demonstrated that cardiopulmonary exercise testing showed better ventilatory responses and decreased oxygen saturation.

Furthermore, Holland et al.[20] revealed that cardiopulmonary exercise testing had a significantly lower ventilation peak, carbon dioxide production, and higher peak oxygen uptake, especially in advanced stages of the disease. On the other hand, the 6-min walk test showed high, yet, submaximal oxygen uptake. Holland et al.[20] recommended that the 6-min walk test should not usually be used for submaximal exercise capacity in interstitial lung disease compared to cardiopulmonary exercise testing.

Additionally, Blanco et al.[18] compared the physiological alterations in patients with interstitial lung disease and high pulmonary artery pressure using cardiopulmonary exercise testing compared to the 6-min walk test. Blanco et al.[18] showed that both tests had similar physiological changes in terms of oxygen consumption and arterial oxygen saturation.

It is worth to mention that some studies used cardiopulmonary exercise testing to compare changes between patients with interstitial lung diseases with or without pulmonary artery hypertension.

Armstrong et al.[16] examined the correlation between cardiopulmonary exercise testing and pulmonary artery hypertension in interstitial lung disease patients. Armstrong et al.[16] illustrated that cardiopulmonary exercise testing abnormalities are correlated to pulmonary artery hypertension, and it can identify different severity levels through the ratio of minute ventilation to rate of carbon dioxide production and end-tidal carbon dioxide partial pressure.

Similarly, Degani-Costa et al.[19] supported the findings of Armstrong et al.[16] in confirming the predictive abilities of cardiopulmonary exercise testing in patients with interstitial lung disease especially in the presence of pulmonary artery hypertension. Although Degani-Costa et al.[19] showed that these prognostic benefits are only confirmed with invasive cardiopulmonary exercise testing compared to other noninvasive techniques.

In another study, Armstrong et al.[21] showed that the presence or absence of pulmonary artery hypertension could be identified in patients with interstitial lung diseases using cardiopulmonary exercise testing. Also, Holland et al.[17] correlated reduced chronotropic response on cardiopulmonary exercise testing with reduced survival in interstitial lung diseases patients.

However, the included trials had some limitations; some of the included studies were retrospective,[16],[21] which could question the outcomes of their findings. Also, all the studies had a small number of patients,[16],[17],[18],[19],[20],[21],[22] with a maximum number of patients is 72. These limitations should be considered in future studies. In addition, this review is limited by the design of the included studies, where only two studies had a randomized controlled design.[18],[19] This limitation highlights the emergent need for more studies with robust design to confirm the clinical utility of cardiopulmonary exercise testing in patients with interstitial lung diseases.

From the present review, we can conclude that the use cardiopulmonary exercise testing can play a better prognostic role in patients with interstitial lung disease at early stages compared to conventional tests such as 6-min walk test. Cardiopulmonary exercise testing can evaluate oxygen uptake, arterial oxygen saturation, mean pulmonary artery pressure, carbon dioxide formation, and expiration and end-tidal carbon dioxide pressure, yet, further studies with larger sample studies are warranted to confirm these outcomes and to compare invasive versus noninvasive cardiopulmonary exercise testing.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Armstrong HF, Schulze PC, Bacchetta M, Thirapatarapong W, Bartels MN. Impact of pulmonary hypertension on exercise performance in patients with interstitial lung disease undergoing evaluation for lung transplantation. Respirology 2014;19:675-82.  Back to cited text no. 16
    
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Holland AE, Hill CJ, Glaspole I, Goh N, Dowman L, McDonald CF. Impaired chronotropic response to 6-min walk test and reduced survival in interstitial lung disease. Respir Med 2013;107:1066-72.  Back to cited text no. 17
    
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