Intensity of physical exercise and its effect on functional capacity in COPD: systematic review and meta-analysis

Juliano Rodrigues Adolfo William Dhein Graciele Sbruzzi About the authors

ABSTRACT

Objective:

To evaluate the effects of high-intensity interval training (HIIT), in comparison with those of continuous exercise, on functional capacity and cardiovascular variables in patients with COPD, through a systematic review and meta-analysis of randomized controlled trials.

Methods:

We searched PubMed, the Physiotherapy Evidence Database, the Cochrane Central Register of Controlled Trials, and EMBASE, as well as performing hand searches, for articles published up through January of 2017. We included studies comparing exercise regimens of different intensities, in terms of their effects on functional capacity and cardiovascular variables in patients with COPD.

Results:

Of the 78 articles identified, 6 were included in the systematic review and meta-analysis. Maximal oxygen consumption (VO2max) did not differ significantly between HIIT and control interventions. That was true for relative VO2max (0.03 mL/kg/min; 95% CI: −3.05 to 3.10) and absolute VO2max (0.03 L/min, 95% CI: −0.02 to 0.08).

Conclusions:

The effects of HIIT appear to be comparable to those of continuous exercise in relation to functional and cardiovascular responses. However, our findings should be interpreted with caution because the studies evaluated present a high risk of bias, which could have a direct influence on the results.

Keywords:
Pulmonary disease, chronic obstructive; Exercise; Oxygen consumption

RESUMO

Objetivo:

Avaliar e comparar os efeitos do high-intensity interval training (HIIT, treinamento intervalado de alta intensidade) aos do exercício contínuo sobre a capacidade funcional e variáveis cardiovasculares em pacientes com DPOC por meio de revisão sistemática e meta-análise de estudos controlados randomizados.

Métodos:

A busca incluiu as bases PubMed, Physiotherapy Evidence Database, Cochrane Central Register of Controlled Trials e EMBASE, além de busca manual, até janeiro de 2017. Foram incluídos estudos que compararam os efeitos de diferentes intensidades de exercício em pacientes com DPOC sobre a capacidade funcional e variáveis cardiovasculares.

Resultados:

Dos 78 artigos identificados, 6 foram incluídos na revisão sistemática e meta-análise. Em relação ao consumo máximo de oxigênio (VO2máx), foi observado que não houve diferenças entre o HIIT e outra intervenção no VO2máx relativo (0,03 ml/kg/min; IC95%: −3,05 a 3,10) e VO2máx absoluto (0,03 l/min; IC95%: −0,02 a 0,08).

Conclusões:

O HIIT e o exercício contínuo atuam de maneira semelhante em relação a respostas funcionais e cardiovasculares. Entretanto, os resultados apresentados devem ser analisados com cautela, pois os estudos incluídos apresentaram alto risco de viés, podendo influenciar diretamente seus resultados.

Descritores:
Doença pulmonar obstrutiva crônica; Exercício; Consumo de oxigênio

INTRODUCTION

Because COPD has systemic involvement and is an important risk factor for other comorbidities, it has a growing impact worldwide,11 Global Initiative for Chronic Obstructive Lung Disease (GOLD) [homepage on the Internet]. Bethesda: GOLD [cited 2018 Jun 10]. Global Strategy for the Diagnosis, Management, and Prevention of COPD - 2018 Report. [Adobe Acrobat document, 155p.]. Available from: https://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf
https://goldcopd.org/wp-content/uploads/...
and chronic airflow limitation due to abnormality in the alveolar airways is its most striking characteristic, the major symptom of which is dyspnea,22 Borel B, Provencher S, Saey D, Maltais F. Responsiveness of Various Exercise-Testing Protocols to Therapeutic Interventions in COPD. Pulm Med. 2013;2013:410748. https://doi.org/10.1155/2013/410748
https://doi.org/10.1155/2013/410748...
resulting from genetic deficiency (alpha-1 antitrypsin deficiency), outdoor or indoor air pollution (related to firewood burning), significant exposure to noxious particles or gases (such as cigarette smoke), etc. However, COPD can no longer be considered a disease presenting with pulmonary involvement alone.33 Carreiro A, Santos J, Rodrigues F. Impact of comorbidities in pulmonary rehabilitation outcomes in patients with chronic obstructive pulmonary disease. Rev Port Pneumol. 2013;19(3):106-13. https://doi.org/10.1016/j.rppneu.2012.12.004
https://doi.org/10.1016/j.rppneu.2012.12...

Exercise intolerance is a consequence of COPD, leading the patient to a sedentary lifestyle to avoid exercise-induced dyspnea. The association of physical inactivity with the metabolic disorders and structural changes caused by the disease, as well as the fact that smoking is also a primary cause, results in there being multiple risk factors for cardiovascular disease in this population.44 Gale N, Duckers JM, Enright S, Cockcroft JR, Shale DJ, Bolton CE. Does pulmonary rehabilitation address cardiovascular risk factors in patients with COPD? BMC Pulm Med. 2011;11:20. https://doi.org/10.1186/1471-2466-11-20
https://doi.org/10.1186/1471-2466-11-20...
In addition, COPD is a powerful independent risk factor for cardiovascular morbidity and mortality,55 Castagna O, Boussuges A, Nussbaum E, Marqueste L, Brisswalter J. Peripheral arterial disease: an underestimated aetiology of exercise intolerance in chronic obstructive pulmonary disease patients. Eur J Cardiovasc Prev Rehabil. 2008;15(3):270-7. https://doi.org/10.1097/HJR.0b013e3282f009a9
https://doi.org/10.1097/HJR.0b013e3282f0...
since the major risk factors for cardiovascular disease are also present in these patients.66 Müllerova H, Agusti A, Ergou S, Mapel DW. Cardiovascular comorbidity in COPD: systematic literature review. Chest. 2013;144(4):1163-1178. https://doi.org/10.1378/chest.12-2847
https://doi.org/10.1378/chest.12-2847...

Physical exercise is an integral part of pulmonary rehabilitation programs. The principles of training are exercise duration, frequency, progression, modality, individualization, and, especially, intensity, which is recognized as the key determinant of the physiological benefits gained from rehabilitation.77 Tanaka H, Monahan KD, Seals DR. Age-predicted maximal heart rate revisited. J Am Coll Cardiol. 2001;37(1):153-6. https://doi.org/10.1016/S0735-1097(00)01054-8
https://doi.org/10.1016/S0735-1097(00)01...
According to the American College of Sports Medicine,88 Ferguson B. ACSM's Guidelines for Exercise Testing and Prescription. J Can Chiropr Assoc [serial on the Internet]. 2014 Sep [cited 2018 Jun 10];58(3):[about 3 p.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139760
https://www.ncbi.nlm.nih.gov/pmc/article...
moderate-intensity continuous aerobic exercise for 20 to 60 min per session brings physiological benefits, whether on a treadmill or a cycle ergometer, the latter resulting in lower exercise-induced oxygen desaturation in the training of patients with COPD. High-intensity interval training (HIIT) can be an alternative to continuous exercise training for individuals with COPD who have difficulty reaching the target duration because of dyspnea, fatigue, or any other symptom.99 Spruit MA, Singh JS, Garvey C, ZuWallack R, Nici L, Rochester C, et al. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med. 2013;188(8):e13-64. https://doi.org/10.1164/rccm.201309-1634ST
https://doi.org/10.1164/rccm.201309-1634...

To date, there have been few studies correlating COPD and the effects of HIIT in pulmonary rehabilitation in terms of cardiovascular variables and functional capacity. One study describing the effects of two training programs in patients with COPD indicated improvement in functional capacity after 12 weeks of high-intensity training.1010 Camilo CA, Luburu Vde M, Gonçalves NS, Cavalhieri V, Tomasi FP, Hernandes NA, et al. Improvement of heart rate variability after exercise training and its predictors in COPD. Respir Med. 2011;105(7):1054-62. https://doi.org/10.1016/j.rmed.2011.01.014
https://doi.org/10.1016/j.rmed.2011.01.0...
One study evaluating improvement in systolic function in patients with COPD reported that the effects of HIIT and of moderate exercise result in positive changes in cardiovascular values.1111 Probst VS, Kovelis D, Hernandes NA, Camillo CA, Cavalheri V, Pitta F. Effects of 2 exercise training programs on physical activity in daily life in patients with COPD. Respir Care. 2011;56(11):1799-807. https://doi.org/10.4187/respcare.01110
https://doi.org/10.4187/respcare.01110...
A study analyzing heart rate variability after HIIT in patients with COPD reported improvement in autonomic cardiac function after three months of HIIT.1212 Puhan MA, Büsching G, Schünemann HJ, VanOort E, Zaugg C, Frey M. Interval versus continuous high-intensity exercise in chronic obstructive pulmonary disease. Ann Intern Med. 2006;145(11):816-25. https://doi.org/10.7326/0003-4819-145-11-200612050-00006
https://doi.org/10.7326/0003-4819-145-11...
In addition, a systematic review of studies on changes in ventilatory parameters in patients with moderate to severe COPD, who participated in pulmonary rehabilitation programs, evaluated exercise mode, frequency, duration, and intensity. Patients were shown to be able to perform HIIT, which resulted in positive changes in ventilatory parameters and in reduced exercise-related dyspnea.1313 Osterling K, MacFadyen K, Gilbert R, Dechman G. The effects of high intensity exercise during pulmonary rehabilitation on ventilatory parameters in people with moderate to severe stable COPD: a systematic review. Int J Chron Obstruct Pulmon Dis. 2014;9:1069-78. https://doi.org/10.2147/COPD.S68011
https://doi.org/10.2147/COPD.S68011...

Therefore, the present study plays an important role in improving scientific knowledge on the contributions of different intensities of aerobic exercise to cardiovascular health in individuals with COPD, given that the most recent systematic review on the subject was published in 2014 and evaluated only ventilatory outcomes. The objective of the present study was to systematically review the effects of HIIT, in comparison with those of continuous aerobic exercise or any other control intervention, on functional capacity and cardiovascular variables in patients with COPD.

METHODS

The study was conducted in accordance with the PRISMA Statement1414 Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100. https://doi.org/10.1371/journal.pmed.1000100
https://doi.org/10.1371/journal.pmed.100...
and was registered with the International Prospective Register of Systematic Reviews (PROSPERO; Protocol no. 42017056753).

Eligibility criteria and search strategy

We included randomized controlled trials that addressed the use of HIIT in patients with COPD, in comparison with the use of moderate-intensity continuous aerobic exercise or any other control intervention, on functional capacity, as measured by maximal oxygen consumption (VO2max), six-minute walk distance (6MWD), and Borg dyspnea and leg fatigue scores, as well as on cardiovascular variables, such as endothelial function, ankle-brachial index, systolic blood pressure, diastolic blood pressure, HR, RR, and SpO2. We included studies that used different HIIT modalities, such as treadmill or cycle ergometer training. We excluded articles that evaluated patients with an exercise-limiting disease or medical condition.

We searched the following electronic databases (from inception through January of 2017): PubMed; Physiotherapy Evidence Database; Cochrane Central Register of Controlled Trials; and EMBASE. In addition, we hand searched the references in published studies on the subject. Our search was performed on January 27, 2017 and included the keywords “high intensity interval training” and “pulmonary disease, chronic obstructive”, as well as the corresponding keywords in Portuguese “treinamento intervalado de alta intensidade” and “doença pulmonar obstrutiva crônica”. The keywords were combined with a sensitive list of terms for searching for randomized controlled trials that was compiled by Robinson & Dickersin.1515 Robinson KA, Dickersin K. Development of a highly sensitive search strategy for the retrieval of reports of controlled trials using PubMed. Int J Epidemiol. 2002;31(1):150-3. https://doi.org/10.1093/ije/31.1.150
https://doi.org/10.1093/ije/31.1.150...
Our search had no language restriction and was performed after the study had been registered with PROSPERO. Full articles published in journals and accepted papers were taken into account. The full search strategy used in PubMed is shown in Chart S1.

Chart S1
Search strategy.

STUDY SELECTION AND DATA EXTRACTION

The titles and abstracts of all articles identified by the search strategy were evaluated independently and in duplicate by two reviewers. All abstracts that did not provide sufficient information about the inclusion and exclusion criteria were selected for full-text evaluation. In this second phase, the same reviewers independently evaluated the full texts and made their selections based on the pre-specified eligibility criteria. Disagreements between reviewers were resolved by consensus.

Using standardized electronic forms, the same two reviewers independently extracted data on the methodological characteristics of the studies, interventions, and results. Differences were again resolved by consensus.

Initially, the studies were assessed for the following: authors; year of publication; sample (total number of subjects); methodology; HIIT intervention protocol; control group; comparator protocol (if any); evaluated outcomes; results; and conclusions. The primary outcome extracted was VO2max (in mL/kg/min and L/min). The secondary outcomes evaluated in the present study were 6MWD and the aforementioned cardiovascular variables.

Evaluation of risk of bias and data analysis

The evaluation of study quality was performed descriptively and included the following characteristics: adequate generation of randomization sequences; concealment of allocation; blinding; blinding of outcome assessors; intention-to-treat analysis; and reporting of losses and exclusions. All characteristics that were not clearly reported were classified as “no data”.

The use of intention-to-treat analysis in a study was considered as confirmation that the number of randomized participants was the same as the number of analyzed participants. Studies without this characteristic were considered not to meet this criterion. Study quality was evaluated independently by the same two reviewers.

Meta-analysis was performed using the random-effects model, and effect measures were calculated as the mean difference between baseline and follow-up values. An α value = 0.05 was considered statistically significant. Statistical heterogeneity of treatment effect across studies was assessed using the inconsistency I2 test, in which values above 25% and 50% were considered to be indicative of moderate and high heterogeneity, respectively. All analyses were conducted with the software Review Manager, version 5.3 (RevMan 5; Cochrane Collaboration, Oxford, UK).

RESULTS

The initial search identified 78 articles, of which 49 were retrieved for detailed analysis. Of those, 17 were considered potentially relevant. However, 11 studies were excluded: those by Nasis et al.,1616 Nasis I, Kortianou E, Vasilopoulou M, Spetsioti S, Louvaris Z, Kaltsakas G, et al. Hemodynamic effects of high intensity interval training in COPD patients exhibiting exercise-induced dynamic hyperinflation. Respir Physiol Neurobiol. 2015;217:8-16. https://doi.org/10.1016/j.resp.2015.06.006
https://doi.org/10.1016/j.resp.2015.06.0...
Hsieh et al.,1717 Hsieh MJ, Lan CC, Chen NH, Huang CC, Wu YK, Cho HY, et al. Effects of high-intensity exercise training in a pulmonary rehabilitation programme for patients with chronic obstructive pulmonary disease. Respirology. 2007;12(3):381-8. https://doi.org/10.1111/j.1440-1843.2007.01077.x
https://doi.org/10.1111/j.1440-1843.2007...
Pitta et al.,1818 Pitta F, Brunetto AF, Padovani CR, Godoy I. Effects of isolated cycle ergometer training on patients with moderate-to-severe chronic obstructive pulmonary disease. Respiration. 2004;71(5):477-83. https://doi.org/10.1159/000080632
https://doi.org/10.1159/000080632...
Rodríguez et al.,1919 Rodríguez DA, Arbillaga A, Barberan-Garcia A, Ramirez-Sarmiento A, Torralba Y, Vilaró J, et al. Effects of interval and continuous exercise training on autonomic cardiac function in COPD patients. Clin Respir J. 2016;10(1):83-9. https://doi.org/10.1111/crj.12189
https://doi.org/10.1111/crj.12189...
and Varga et al.,2020 Varga J, Porszasz J, Boda K, Casaburi R, Somfay A. Supervised high intensity continuous and interval training vs. self-paced training in COPD. Respir Med. 2007;101(11):2297-304. https://doi.org/10.1016/j.rmed.2007.06.017
https://doi.org/10.1016/j.rmed.2007.06.0...
because they were quasi-experimental studies; that by Camilo et al.,1010 Camilo CA, Luburu Vde M, Gonçalves NS, Cavalhieri V, Tomasi FP, Hernandes NA, et al. Improvement of heart rate variability after exercise training and its predictors in COPD. Respir Med. 2011;105(7):1054-62. https://doi.org/10.1016/j.rmed.2011.01.014
https://doi.org/10.1016/j.rmed.2011.01.0...
because the outcomes of interest were not reported; those by Probst et al.,1111 Probst VS, Kovelis D, Hernandes NA, Camillo CA, Cavalheri V, Pitta F. Effects of 2 exercise training programs on physical activity in daily life in patients with COPD. Respir Care. 2011;56(11):1799-807. https://doi.org/10.4187/respcare.01110
https://doi.org/10.4187/respcare.01110...
Puhan et al.,1212 Puhan MA, Büsching G, Schünemann HJ, VanOort E, Zaugg C, Frey M. Interval versus continuous high-intensity exercise in chronic obstructive pulmonary disease. Ann Intern Med. 2006;145(11):816-25. https://doi.org/10.7326/0003-4819-145-11-200612050-00006
https://doi.org/10.7326/0003-4819-145-11...
and Pomidori et al.,2121 Pomidori L, Contoli M, Mandolesi G, Cogo A. A simple method for home exercise training in patients with chronic obstructive pulmonary disease. J Cardiopulm Rehabil Prev. 2012;32(1):53-7. https://doi.org/10.1097/HCR.0b013e31823be0ce
https://doi.org/10.1097/HCR.0b013e31823b...
because the training performed was not consistent with the definition of HIIT; that by Mador et al.,2222 Mador MJ, Krawza M, Alhajhusian A, Khan AI, Shaffer M, Kufel TJ. Interval training versus continuous training in patients with chronic obstructive pulmonary disease. J Cardiopulm Rehabil Prev. 2009;29(2):126-32. https://doi.org/10.1097/HCR.0b013e31819a024f
https://doi.org/10.1097/HCR.0b013e31819a...
because the training did not fit within the upper limits defining HIIT; and that by Coppoolse et al.,2323 Coppoolse R, Schols AM, Baarends EM, Mostert R, Akkermans MA, Janssen PP, et al. Interval versus continuous training in patients with severe COPD: a randomized clinical trial. Eur Respir J. 1999;14(2):258-63. https://doi.org/10.1034/j.1399-3003.1999.14b04.x
https://doi.org/10.1034/j.1399-3003.1999...
because HIIT was combined with another intervention. Therefore, 6 studies investigating a total of 295 patients were included in the systematic review and meta-analysis. Figure 1 provides a study inclusion flow chart, and Table 1 summarizes the characteristics of the included studies.

Figure 1
Study inclusion flow chart. RCT: randomized controlled trial; and HIIT: high-intensity interval training.

Table 1
Characteristics of the included studies.

According to the inclusion criteria in the studies, the selected COPD patients were staged based on the presence of a post-bronchodilator FEV1 ≥ 30% and < 80% of predicted and an FEV1/FVC ratio < 70%, as per the Global Initiative for Chronic Obstructive Lung Disease,11 Global Initiative for Chronic Obstructive Lung Disease (GOLD) [homepage on the Internet]. Bethesda: GOLD [cited 2018 Jun 10]. Global Strategy for the Diagnosis, Management, and Prevention of COPD - 2018 Report. [Adobe Acrobat document, 155p.]. Available from: https://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf
https://goldcopd.org/wp-content/uploads/...
as having grade II or III disease (moderate or severe disease, respectively).2424 Hentschel M, Becker J, Lepthin HJ. Effects of a high intensity training program on patients with chronic obstructive airways disease (COAD) [Article in German]. Pneumologie. 2002;56(4):240-6. https://doi.org/10.1055/s-2002-25073
https://doi.org/10.1055/s-2002-25073...

25 Arnardóttir RH, Boman G, Larsson K, Hedenström H, Emtner M. Interval training compared with continuous training in patients with COPD. Respir Med. 2007;101(6):1196-204. https://doi.org/10.1016/j.rmed.2006.11.004
https://doi.org/10.1016/j.rmed.2006.11.0...

26 Vogiatzis I, Nanas S, Roussos C. Interval training as an alternative modality to continuous exercise in patients with COPD. Eur Respir J. 2002;20(1):12-9. https://doi.org/10.1183/09031936.02.01152001
https://doi.org/10.1183/09031936.02.0115...

27 Vogiatzis I, Terzis Z, Nanas S, Stratakos G, Simoes DC, Geordiadou O, et al. Skeletal muscle adaptations to interval training in patients with advanced COPD. Chest. 2005;128(6):3838-45. https://doi.org/10.1378/chest.128.6.3838
https://doi.org/10.1378/chest.128.6.3838...

28 Normandin EA, McCusker C, Connors M, Vale F, Gerardi D, ZuWallack RL. An evaluation of two approaches to exercise conditioning in pulmonary rehabilitation. Chest. 2002;121(4):1085-91. https://doi.org/10.1378/chest.121.4.1085
https://doi.org/10.1378/chest.121.4.1085...
-2929 Brønstad E, Tjonna AE, Rognmo Ø, Dalen H, Heggli AM, Wisloff U, et al. Aerobic exercise training improves right- and left ventricular systolic function in patients with COPD. COPD. 2013;10(3):300-6. https://doi.org/10.3109/15412555.2012.745843
https://doi.org/10.3109/15412555.2012.74...

Four studies compared HIIT with a rehabilitation program that included psychological support, endurance training, breathing exercises, COPD education, and relaxation (total sample of 238 individuals, of whom 140 were in the HIIT group).2424 Hentschel M, Becker J, Lepthin HJ. Effects of a high intensity training program on patients with chronic obstructive airways disease (COAD) [Article in German]. Pneumologie. 2002;56(4):240-6. https://doi.org/10.1055/s-2002-25073
https://doi.org/10.1055/s-2002-25073...

25 Arnardóttir RH, Boman G, Larsson K, Hedenström H, Emtner M. Interval training compared with continuous training in patients with COPD. Respir Med. 2007;101(6):1196-204. https://doi.org/10.1016/j.rmed.2006.11.004
https://doi.org/10.1016/j.rmed.2006.11.0...

26 Vogiatzis I, Nanas S, Roussos C. Interval training as an alternative modality to continuous exercise in patients with COPD. Eur Respir J. 2002;20(1):12-9. https://doi.org/10.1183/09031936.02.01152001
https://doi.org/10.1183/09031936.02.0115...
-2727 Vogiatzis I, Terzis Z, Nanas S, Stratakos G, Simoes DC, Geordiadou O, et al. Skeletal muscle adaptations to interval training in patients with advanced COPD. Chest. 2005;128(6):3838-45. https://doi.org/10.1378/chest.128.6.3838
https://doi.org/10.1378/chest.128.6.3838...
One study compared HIIT with low-intensity continuous exercise,2828 Normandin EA, McCusker C, Connors M, Vale F, Gerardi D, ZuWallack RL. An evaluation of two approaches to exercise conditioning in pulmonary rehabilitation. Chest. 2002;121(4):1085-91. https://doi.org/10.1378/chest.121.4.1085
https://doi.org/10.1378/chest.121.4.1085...
whereas another 1 compared HIIT with moderate-intensity continuous exercise.2929 Brønstad E, Tjonna AE, Rognmo Ø, Dalen H, Heggli AM, Wisloff U, et al. Aerobic exercise training improves right- and left ventricular systolic function in patients with COPD. COPD. 2013;10(3):300-6. https://doi.org/10.3109/15412555.2012.745843
https://doi.org/10.3109/15412555.2012.74...

Of the studies included in this systematic review, 4 (67%) had adequate randomization or reported randomization, having a low risk of bias; only 1 reported allocation concealment, and 1 reported blinding of outcome assessors, but only for one variable, having a high risk of bias; 5 described losses to follow-up and exclusions, having a low risk of bias; and none performed or reported intention-to-treat analysis, having a high risk of bias (Table 2).

Table 2
Evaluation of risk of bias.

In relation to the effects of the interventions, 3 studies2424 Hentschel M, Becker J, Lepthin HJ. Effects of a high intensity training program on patients with chronic obstructive airways disease (COAD) [Article in German]. Pneumologie. 2002;56(4):240-6. https://doi.org/10.1055/s-2002-25073
https://doi.org/10.1055/s-2002-25073...
,2525 Arnardóttir RH, Boman G, Larsson K, Hedenström H, Emtner M. Interval training compared with continuous training in patients with COPD. Respir Med. 2007;101(6):1196-204. https://doi.org/10.1016/j.rmed.2006.11.004
https://doi.org/10.1016/j.rmed.2006.11.0...
,2929 Brønstad E, Tjonna AE, Rognmo Ø, Dalen H, Heggli AM, Wisloff U, et al. Aerobic exercise training improves right- and left ventricular systolic function in patients with COPD. COPD. 2013;10(3):300-6. https://doi.org/10.3109/15412555.2012.745843
https://doi.org/10.3109/15412555.2012.74...
determined relative VO2max (n = 200) and 3 studies2626 Vogiatzis I, Nanas S, Roussos C. Interval training as an alternative modality to continuous exercise in patients with COPD. Eur Respir J. 2002;20(1):12-9. https://doi.org/10.1183/09031936.02.01152001
https://doi.org/10.1183/09031936.02.0115...

27 Vogiatzis I, Terzis Z, Nanas S, Stratakos G, Simoes DC, Geordiadou O, et al. Skeletal muscle adaptations to interval training in patients with advanced COPD. Chest. 2005;128(6):3838-45. https://doi.org/10.1378/chest.128.6.3838
https://doi.org/10.1378/chest.128.6.3838...
-2828 Normandin EA, McCusker C, Connors M, Vale F, Gerardi D, ZuWallack RL. An evaluation of two approaches to exercise conditioning in pulmonary rehabilitation. Chest. 2002;121(4):1085-91. https://doi.org/10.1378/chest.121.4.1085
https://doi.org/10.1378/chest.121.4.1085...
determined absolute VO2max (n = 95). In both analyses, there was no significant difference between the HIIT groups and the control groups (relative VO2max = 0.03 mL/kg/min; 95% CI: −3.05 to 3.10; I2: 92%; and absolute VO2max = 0.03 L/min; 95% CI: −0.02 to 0.08; I2: 34%; Figures 2A and 2B).

Figure 2
Comparison between the effects of HIIT and those of continuous exercise and rehabilitation on relative VO2max (in A) and absolute VO2max (in B). HIIT: high-intensity interval training; and VO2max: maximal oxygen consumption.

On the basis of relative VO2max, it is possible to identify similarities across studies,2424 Hentschel M, Becker J, Lepthin HJ. Effects of a high intensity training program on patients with chronic obstructive airways disease (COAD) [Article in German]. Pneumologie. 2002;56(4):240-6. https://doi.org/10.1055/s-2002-25073
https://doi.org/10.1055/s-2002-25073...
,2525 Arnardóttir RH, Boman G, Larsson K, Hedenström H, Emtner M. Interval training compared with continuous training in patients with COPD. Respir Med. 2007;101(6):1196-204. https://doi.org/10.1016/j.rmed.2006.11.004
https://doi.org/10.1016/j.rmed.2006.11.0...
,2929 Brønstad E, Tjonna AE, Rognmo Ø, Dalen H, Heggli AM, Wisloff U, et al. Aerobic exercise training improves right- and left ventricular systolic function in patients with COPD. COPD. 2013;10(3):300-6. https://doi.org/10.3109/15412555.2012.745843
https://doi.org/10.3109/15412555.2012.74...
especially in relation to the duration of each session (40, 39, and 38 min, respectively). Intervention duration ranged from 22 to 28 sessions. The type of training in the intervention group was similar across studies: aerobic cycling exercise2525 Arnardóttir RH, Boman G, Larsson K, Hedenström H, Emtner M. Interval training compared with continuous training in patients with COPD. Respir Med. 2007;101(6):1196-204. https://doi.org/10.1016/j.rmed.2006.11.004
https://doi.org/10.1016/j.rmed.2006.11.0...
; aerobic exercise on a treadmill2929 Brønstad E, Tjonna AE, Rognmo Ø, Dalen H, Heggli AM, Wisloff U, et al. Aerobic exercise training improves right- and left ventricular systolic function in patients with COPD. COPD. 2013;10(3):300-6. https://doi.org/10.3109/15412555.2012.745843
https://doi.org/10.3109/15412555.2012.74...
; and aerobic exercise on a cycle ergometer.2424 Hentschel M, Becker J, Lepthin HJ. Effects of a high intensity training program on patients with chronic obstructive airways disease (COAD) [Article in German]. Pneumologie. 2002;56(4):240-6. https://doi.org/10.1055/s-2002-25073
https://doi.org/10.1055/s-2002-25073...
However, the control groups are noteworthy: 2 studies2525 Arnardóttir RH, Boman G, Larsson K, Hedenström H, Emtner M. Interval training compared with continuous training in patients with COPD. Respir Med. 2007;101(6):1196-204. https://doi.org/10.1016/j.rmed.2006.11.004
https://doi.org/10.1016/j.rmed.2006.11.0...
,2929 Brønstad E, Tjonna AE, Rognmo Ø, Dalen H, Heggli AM, Wisloff U, et al. Aerobic exercise training improves right- and left ventricular systolic function in patients with COPD. COPD. 2013;10(3):300-6. https://doi.org/10.3109/15412555.2012.745843
https://doi.org/10.3109/15412555.2012.74...
used a similar moderate-intensity intervention in the control group and reported no differences between the intervention and control groups; and 1 study2424 Hentschel M, Becker J, Lepthin HJ. Effects of a high intensity training program on patients with chronic obstructive airways disease (COAD) [Article in German]. Pneumologie. 2002;56(4):240-6. https://doi.org/10.1055/s-2002-25073
https://doi.org/10.1055/s-2002-25073...
used a mix of interventions in the control group-patient education, drug therapy, breathing exercises, physical therapy, and nutrition-showing that the HIIT group was superior to the control group.

The studies2626 Vogiatzis I, Nanas S, Roussos C. Interval training as an alternative modality to continuous exercise in patients with COPD. Eur Respir J. 2002;20(1):12-9. https://doi.org/10.1183/09031936.02.01152001
https://doi.org/10.1183/09031936.02.0115...

27 Vogiatzis I, Terzis Z, Nanas S, Stratakos G, Simoes DC, Geordiadou O, et al. Skeletal muscle adaptations to interval training in patients with advanced COPD. Chest. 2005;128(6):3838-45. https://doi.org/10.1378/chest.128.6.3838
https://doi.org/10.1378/chest.128.6.3838...
-2828 Normandin EA, McCusker C, Connors M, Vale F, Gerardi D, ZuWallack RL. An evaluation of two approaches to exercise conditioning in pulmonary rehabilitation. Chest. 2002;121(4):1085-91. https://doi.org/10.1378/chest.121.4.1085
https://doi.org/10.1378/chest.121.4.1085...
that determined absolute VO2max reported a total training session duration of 30-45 min and an intervention duration of 16-30 sessions. In 1 of those studies,2828 Normandin EA, McCusker C, Connors M, Vale F, Gerardi D, ZuWallack RL. An evaluation of two approaches to exercise conditioning in pulmonary rehabilitation. Chest. 2002;121(4):1085-91. https://doi.org/10.1378/chest.121.4.1085
https://doi.org/10.1378/chest.121.4.1085...
the control group performed low-intensity continuous exercise, whereas in 2,2626 Vogiatzis I, Nanas S, Roussos C. Interval training as an alternative modality to continuous exercise in patients with COPD. Eur Respir J. 2002;20(1):12-9. https://doi.org/10.1183/09031936.02.01152001
https://doi.org/10.1183/09031936.02.0115...
,2727 Vogiatzis I, Terzis Z, Nanas S, Stratakos G, Simoes DC, Geordiadou O, et al. Skeletal muscle adaptations to interval training in patients with advanced COPD. Chest. 2005;128(6):3838-45. https://doi.org/10.1378/chest.128.6.3838
https://doi.org/10.1378/chest.128.6.3838...
the control group underwent cycle ergometer training using parameters that were very close to those used in the intervention group. Although those studies found no differences between the intervention and control groups, 1 of the studies2626 Vogiatzis I, Nanas S, Roussos C. Interval training as an alternative modality to continuous exercise in patients with COPD. Eur Respir J. 2002;20(1):12-9. https://doi.org/10.1183/09031936.02.01152001
https://doi.org/10.1183/09031936.02.0115...
reported a trend toward the superiority of the HIIT group over the control group (low-intensity exercise).

None of the included studies evaluated 6MWD, ankle-brachial index, Borg dyspnea scores, or SpO2. Only 1 study2929 Brønstad E, Tjonna AE, Rognmo Ø, Dalen H, Heggli AM, Wisloff U, et al. Aerobic exercise training improves right- and left ventricular systolic function in patients with COPD. COPD. 2013;10(3):300-6. https://doi.org/10.3109/15412555.2012.745843
https://doi.org/10.3109/15412555.2012.74...
evaluated endothelial function, and the authors found that there were no intragroup or intergroup differences in this variable.

Only 1 study2929 Brønstad E, Tjonna AE, Rognmo Ø, Dalen H, Heggli AM, Wisloff U, et al. Aerobic exercise training improves right- and left ventricular systolic function in patients with COPD. COPD. 2013;10(3):300-6. https://doi.org/10.3109/15412555.2012.745843
https://doi.org/10.3109/15412555.2012.74...
evaluated systolic and diastolic blood pressures and found that there were no pre- or post-intervention differences within the groups and no differences between the groups. Two studies2424 Hentschel M, Becker J, Lepthin HJ. Effects of a high intensity training program on patients with chronic obstructive airways disease (COAD) [Article in German]. Pneumologie. 2002;56(4):240-6. https://doi.org/10.1055/s-2002-25073
https://doi.org/10.1055/s-2002-25073...
,2929 Brønstad E, Tjonna AE, Rognmo Ø, Dalen H, Heggli AM, Wisloff U, et al. Aerobic exercise training improves right- and left ventricular systolic function in patients with COPD. COPD. 2013;10(3):300-6. https://doi.org/10.3109/15412555.2012.745843
https://doi.org/10.3109/15412555.2012.74...
evaluated HR, and 1 of the studies2929 Brønstad E, Tjonna AE, Rognmo Ø, Dalen H, Heggli AM, Wisloff U, et al. Aerobic exercise training improves right- and left ventricular systolic function in patients with COPD. COPD. 2013;10(3):300-6. https://doi.org/10.3109/15412555.2012.745843
https://doi.org/10.3109/15412555.2012.74...
found significantly reduced resting HR in both groups (p < 0.05); however, there were no differences between the groups. In 1 study,2424 Hentschel M, Becker J, Lepthin HJ. Effects of a high intensity training program on patients with chronic obstructive airways disease (COAD) [Article in German]. Pneumologie. 2002;56(4):240-6. https://doi.org/10.1055/s-2002-25073
https://doi.org/10.1055/s-2002-25073...
there was an increase in HR in the intervention group (p < 0.01), but there were no differences between the groups.

One of the studies2424 Hentschel M, Becker J, Lepthin HJ. Effects of a high intensity training program on patients with chronic obstructive airways disease (COAD) [Article in German]. Pneumologie. 2002;56(4):240-6. https://doi.org/10.1055/s-2002-25073
https://doi.org/10.1055/s-2002-25073...
evaluated RR and found that there was an increase in RR in the intervention group (p < 0.05); however, there was no difference between the groups. The same study2424 Hentschel M, Becker J, Lepthin HJ. Effects of a high intensity training program on patients with chronic obstructive airways disease (COAD) [Article in German]. Pneumologie. 2002;56(4):240-6. https://doi.org/10.1055/s-2002-25073
https://doi.org/10.1055/s-2002-25073...
evaluated Borg leg fatigue scores and found a decrease in scores in the intervention group (p < 0.01), but there were no differences between the groups.

DISCUSSION

The findings of the present study indicate that the effects of HIIT are comparable to those of continuous exercise or any other control intervention regarding relative VO2max, absolute VO2max, and cardiovascular variables in patients with COPD.

In relation to the type and intensity of exercise that should be included in a pulmonary rehabilitation program, studies have shown positive effects of both HIIT and moderate-intensity continuous exercise in patients with COPD.3030 Helgerud J, Høydal K, Wang E, Karlsen T, Berg P, Bjerkaas M, et al. Aerobic high-intensity intervals improve VO2max more than moderate training. Med Sci Sports Exerc. 2007;39(4):665-71. https://doi.org/10.1249/mss.0b013e3180304570
https://doi.org/10.1249/mss.0b013e318030...
,3131 Xu QF, Yuan W, Zhao XJ, Li B, Wang HY. Exercise-related risk at anaerobic threshold in patients with chronic obstructive pulmonary disease [Article in Chinese]. Zhonghua Jie He He Hu Xi Za Zhi. 2016;39(2):110-2. https://doi.org/10.3760/cma.j.issn.1001-0939.2016.02.008
https://doi.org/10.3760/cma.j.issn.1001-...
In addition, one study2020 Varga J, Porszasz J, Boda K, Casaburi R, Somfay A. Supervised high intensity continuous and interval training vs. self-paced training in COPD. Respir Med. 2007;101(11):2297-304. https://doi.org/10.1016/j.rmed.2007.06.017
https://doi.org/10.1016/j.rmed.2007.06.0...
comparing continuous and interval training in patients with COPD indicated that the physiological effects of the two types of training are similar in these patients.

A clinical trial3232 Stefanelli F, Meoli I, Cobuccio R, Curcio C, Amore D, Casazza D, et al. High-intensity training and cardiopulmonary exercise testing in patients with chronic obstructive pulmonary disease and non-small-cell lung cancer undergoing lobectomy. Eur J Cardiothorac Surg. 2013;44(4):e260-5. https://doi.org/10.1093/ejcts/ezt375
https://doi.org/10.1093/ejcts/ezt375...
showed a reduction in perceived dyspnea, an increase in exercise capacity as measured by VO2max, and an improvement in quality of life in patients with COPD who underwent both low- and high-intensity exercise training. One systematic review3333 Beauchamp MK, Nonoyama M, Goldstein RS, Hill K, Dolmage TE, Mathur S, et al. Interval versus continuous training in individuals with chronic obstructive pulmonary disease--a systematic review. Thorax. 2010;65(2):157-64. https://doi.org/10.1136/thx.2009.123000
https://doi.org/10.1136/thx.2009.123000...
showed that interval and continuous exercise both resulted in improved exercise capacity as measured by 6MWD and in improved quality of life. One study3434 Zainuldin R, Mackey MG, Alison JA. Optimal intensity and type of leg exercise training for people with chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011;(11):CD008008. https://doi.org/10.1002/14651858.CD008008.pub2
https://doi.org/10.1002/14651858.CD00800...
comparing different intensities of exercise showed that continuous and interval exercise both appear to be equally effective in improving 6MWD, symptoms, and quality of life in patients with COPD.

In contrast to the results obtained here, studies1717 Hsieh MJ, Lan CC, Chen NH, Huang CC, Wu YK, Cho HY, et al. Effects of high-intensity exercise training in a pulmonary rehabilitation programme for patients with chronic obstructive pulmonary disease. Respirology. 2007;12(3):381-8. https://doi.org/10.1111/j.1440-1843.2007.01077.x
https://doi.org/10.1111/j.1440-1843.2007...
,3535 Casaburi R, Patessio A, Ioli F, Zanaboni S, Donner CF, Wasserman K. Reductions in exercise lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease. Am Rev Respir Dis. 1991;143(1):9-18. https://doi.org/10.1164/ajrccm/143.1.9
https://doi.org/10.1164/ajrccm/143.1.9...
,3636 Maltais F, LeBlanc P, Jobin J, Berube C, Bruneau J, Carrier R, et al. Intensity of training and physiologic adaptation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1997;155(2):555-61. https://doi.org/10.1164/ajrccm.155.2.9032194
https://doi.org/10.1164/ajrccm.155.2.903...
evaluating the physiological effects of exercise training appear to indicate that these effects are more beneficial in patients who are able to perform higher-intensity exercise than in those who perform lower-intensity exercise. In addition, a systematic review3737 Puhan MA, Schünemann HJ, Frey M, Scharplatz M, Bachmann LM. How should COPD patients exercise during respiratory rehabilitation? Comparison of exercise modalities and intensities to treat skeletal muscle dysfunction. Thorax. 2005;60(5):367-75. https://doi.org/10.1136/thx.2004.033274
https://doi.org/10.1136/thx.2004.033274...
found a significant increase in maximal exercise capacity as measured by 6MWD and a reduction in leg pain only during interval exercise in patients with COPD. Furthermore, a study3030 Helgerud J, Høydal K, Wang E, Karlsen T, Berg P, Bjerkaas M, et al. Aerobic high-intensity intervals improve VO2max more than moderate training. Med Sci Sports Exerc. 2007;39(4):665-71. https://doi.org/10.1249/mss.0b013e3180304570
https://doi.org/10.1249/mss.0b013e318030...
evaluating VO2max at different intensities of exercise showed that the response to HIIT was two to three times greater than the response to low-intensity training (85%-95% and 70% of maximal HR, respectively) in healthy individuals.

Hsieh et al.1717 Hsieh MJ, Lan CC, Chen NH, Huang CC, Wu YK, Cho HY, et al. Effects of high-intensity exercise training in a pulmonary rehabilitation programme for patients with chronic obstructive pulmonary disease. Respirology. 2007;12(3):381-8. https://doi.org/10.1111/j.1440-1843.2007.01077.x
https://doi.org/10.1111/j.1440-1843.2007...
reported that only the patients who were able to perform high-intensity exercise training showed improvements in maximal exercise capacity as measured by VO2max and by 6MWD, in FVC, and in work efficiency. Another study1111 Probst VS, Kovelis D, Hernandes NA, Camillo CA, Cavalheri V, Pitta F. Effects of 2 exercise training programs on physical activity in daily life in patients with COPD. Respir Care. 2011;56(11):1799-807. https://doi.org/10.4187/respcare.01110
https://doi.org/10.4187/respcare.01110...
concluded that high-intensity programs tend to result in significant physiological improvements, being especially efficient in increasing exercise capacity and muscle strength.

In general, the optimal intensity of exercise training depends on the individual goals of each patient, and, if the goal is to increase the ability to perform tasks that are above the current level of tolerance, HIIT appears to elicit greater performance increases because it involves significant anaerobic energy utilization and, therefore, can better mimic the physiological requirements of activities of daily living, is tolerable to patients, and can indeed reduce the degree of dyspnea and dynamic hyperinflation through a reduced ventilatory demand.3838 Butcher SJ, Jones RL. The impact of exercise training intensity on change in physiological function in patients with chronic obstructive pulmonary disease. Sports Med. 2006;36(4):307-25. https://doi.org/10.2165/00007256-200636040-00003
https://doi.org/10.2165/00007256-2006360...

The formulation of the research problem and the development of eligibility criteria were methodologically rigorous. Study selection was performed by two independent reviewers, who also assessed study methodological quality and agreed on the inclusion and exclusion of studies. The use of meta-analysis increases the robustness of evidence on the influence of HIIT on functional and cardiovascular variables.

We found that most of the studies included in the present review had a high or low risk of bias and that none included all items evaluated. For example, only 1 study reported concealment of allocation and blinding of outcome assessors, characteristics that could have a direct influence on the results. Therefore, it is possible that further studies with higher methodological quality in terms of the variables studied will change current findings. Nevertheless, few randomized controlled trials were found, and most of the studies involving HIIT and patients with COPD are quasi-experimental.

Although we found moderate and high heterogeneity in the meta-analyses of VO2max, probably because of the intervention protocols and the control groups (different intensities of continuous exercise), it was not possible to perform sensitivity analyses because of the small number of studies included in each analysis, which makes further analyses difficult.

In conclusion, our findings should be interpreted with caution because the included studies have a high risk of bias, especially in terms of concealment of allocation, blinding of outcome assessors, and intention-to-treat analysis. The lack of these methodological characteristics could have a direct influence on the study results.

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  • 1
    Study carried out under the auspices of the Programa de Pós-Graduação em Ciências do Movimento Humano, Universidade Federal do Rio Grande do Sul, Porto Alegre (RS) Brasil.
  • Financial support:

    None.

Publication Dates

  • Publication in this collection
    26 Sept 2019
  • Date of issue
    2019

History

  • Received
    21 June 2018
  • Accepted
    08 Feb 2019
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