Christopher A. O’Dea1,2*
Michael L. Beaven2,3
Andrew C. Wilson1,2,3
Elizabeth F. Smith2,3
Andrew Maiorana3,4
Shannon J. Simpson2,3
- 1Respiratory Medicine, Perth Children’s Hospital, Perth, WA, Australia
- 2Wal-yan Respiratory Research Centre, Telethon Kids Institute, Perth, WA, Australia
- 3School of Allied Health, Curtin University, Perth, WA, Australia
- 4Department of Allied Health, Fiona Stanley Hospital, Perth, WA, Australia
Objectives: The long-term cardiopulmonary outcomes following preterm birth during the surfactant era remain unclear. Respiratory symptoms, particularly exertional symptoms, are common in preterm children. Therefore, cardiopulmonary exercise testing may provide insights into the pathophysiology driving exertional respiratory symptoms in those born preterm. This review aims to outline the current knowledge of cardiopulmonary exercise testing in the assessment of children born preterm in the surfactant era.
Design: This study is a narrative literature review.
Methods: Published manuscripts concerning the assessment of pulmonary outcomes using cardiopulmonary exercise testing in preterm children (aged <18 years) were reviewed. Search terms related to preterm birth, bronchopulmonary dysplasia, and exercise were entered into electronic databases, including Medline, PubMed, and Google Scholar. Reference lists from included studies were scanned for additional manuscripts.
Results: Preterm children have disrupted lung development with significant structural and functional lung disease and increased respiratory symptoms. The association between these (resting) assessments of respiratory health and exercise capacity is unclear; however, expiratory flow limitation and an altered ventilatory response (rapid, shallow breathing) are seen during exercise. Due to the heterogeneity of participants, treatments, and exercise protocols, the effect of the aforementioned limitations on exercise capacity in children born preterm is conflicting and poorly understood.
Conclusion: Risk factors for reduced exercise capacity in those born preterm remain poorly understood; however, utilizing cardiopulmonary exercise testing to its full potential, the pathophysiology of exercise limitation in survivors of preterm birth will enhance our understanding of the role exercise may play. The role of exercise interventions in mitigating the risk of chronic disease and premature death following preterm birth has yet to be fully realized and should be a focus of future robust randomized controlled trials.
Introduction
Preterm births [less than 37 weeks completed gestational age (GA)] make up approximately 11% of births worldwide (1), with an increased rate of children born preterm reported from 1990 to 2010 (1). Babies surviving preterm birth are at risk of significant health challenges throughout life, including chronic respiratory, neurodevelopmental, and cardiovascular disorders. Long-term health challenges following preterm birth are accentuated in those with bronchopulmonary dysplasia (BPD), a chronic lung disease resulting from the disruption of development and subsequent treatment-induced injury (2). Advancements in neonatal care in the 1990s improved the survival of infants at borderline viable gestational ages, resulting in a change in the pulmonary pathology associated with preterm birth and BPD from the condition first described in the 1960s (3). The hallmark characteristics of contemporary BPD include immature airways, arteries and veins, few or no alveoli, and an inefficient gas exchange area (3). Respiratory health assessments conducted in childhood (4) and young adulthood (5, 6) reveal reduced lung function and structural abnormalities in modern survivors of preterm birth, raising concerns for early-onset adult respiratory disease, including chronic obstructive pulmonary disease (COPD) (7). While the long-term respiratory consequences of preterm birth will likely not be fully realized until the fourth, fifth, and sixth decades of life, recent evidence suggests that infants born preterm in the contemporary era are at risk of developing cardiometabolic diseases in adulthood (8) and increased respiratory morbidity and exertional dyspnea (4, 9, 10). Cardiopulmonary exercise testing (CPET) provides insights into the etiology of cardiopulmonary function following preterm birth and has the potential to identify targets for therapeutic interventions. This narrative review aims to summarize the current knowledge of cardiopulmonary exercise testing in the assessment of pulmonary outcomes in children born preterm in the surfactant era.
Cardiopulmonary exercise testing
CPET assesses the integrative response of the cardiovascular, pulmonary, and skeletal muscle systems to exercise, providing clinical information that may not be apparent at rest. Indeed, health status correlates more strongly with exercise responses than resting measurements across various different pathologies (11). Performing exercise assessments enables the identification of early disrupted physiology and causes of exercise intolerance.
Children born preterm are at higher risk of cardiometabolic diseases (8), such as increased vascular resistance and blood pressure (12), alterations in fat distribution (13), and impaired glucose regulation (14). Understanding the exercise capacity of children born preterm and the systems limiting exercise capacity improves our understanding of deterrents to partaking in physical activity. Importantly, understanding barriers to exercise participation in this population can inform programs designed to mitigate the health risks associated with preterm birth.
Peak aerobic exercise capacity (V̇O2)
Peak V̇O2, a measure of the oxygen uptake of the skeletal muscles, provides a measure of aerobic capacity and is an independent predictor of all-cause mortality (15). Peak V̇O2 independently predicts hospitalizations and future exacerbations in other parenchymal lung diseases such as cystic fibrosis (16–19), and hence, its predictive use in children born preterm has been explored. Data on the aerobic capacity of preterm children born in the surfactant era are conflicting: some studies show a lower peak V̇O2 (10, 20, 21), whereas others have shown no difference (22–26). Comparisons of these studies are difficult due to the variability within the inclusion criteria of the cohorts studied, such as GA, birth weight, the presence and severity of BPD, and the nature of neonatal care.
Neonatal factors associated with lower peak V̇O2
Our literature review shows that the impact of neonatal factors associated with preterm birth on peak V̇O2 is poorly understood. Hochwald et al. reported similar deficits in V̇O2 at peak exercise between participants born early preterm (<30 weeks GA) and late preterm (34–36.6 weeks GA) (27). Several studies have reported no association between peak V̇O2 and the presence or severity of BPD (26, 28). We have previously reported that after accounting for height, weight, and sex, there were no associations between neonatal factors, structural abnormalities on CT, and lung function for V̇O2 at peak exercise (26). Collinearities between gestational age, the severity of BPD, and neonatal interventions, including the duration of mechanical ventilation and supplemental oxygen, make the effect of neonatal histories difficult to elucidate. Consequently, few studies have accurately identified or are able to report the independent effect of gestational age or duration of mechanical ventilation and supplemental oxygen on the aerobic exercise capacity of children born preterm (10, 21, 26).
Association between lung structure and peak V̇O2
Structural lung disease accounts for 42% of the variability in peak V̇O2 in other chronic chest diseases, such as cystic fibrosis, and the total CT score is a stronger predictor for exercise limitation than lung function or body mass (29). To date, only one published study has explored the relationship between structural lung abnormalities in preterm children and exercise capacity, showing no association between peak exercise outcomes and structural lung disease. However, this study did not demonstrate significant exercise impairment in children born preterm (26). Given the high prevalence of exertional symptoms and structural lung disease, an association between exercise capacity and structural lung disease is plausible for children born preterm.
Impact of exercise modality on peak V̇O2
Differences in the methods of exercise testing [e.g., cycle ergometers (10, 21, 23–25, 30, 31), treadmills (9, 22, 28), or shuttle run tests (20, 32–35)] likely contribute to the conflicting outcomes for aerobic capacity in this group. Generally, most treadmill exercise test studies report no difference in aerobic capacity (9, 22), while all studies involving shuttle runs and most studies involving cycle ergometers show lower peak V̇O2 in the preterm population. The varied methodologies of exercise testing make comparisons difficult due to the different advantages and limitations of each method.
Shuttle run assessment
The estimation of peak V̇O2 from shuttle runs involves physical movements that are familiar to children. However, the shuttle run is demanding from a cognitive perspective and may be challenging for preterm children with impaired neurodevelopmental performance (1). Burns et al. (34) reported that motor impairment was the only predictor of estimated peak V̇O2 in extremely low birth weight children, which may suggest that the reductions reported are perhaps due to poor coordination rather than cardiopulmonary limitation. Unfortunately, other factors that may limit exercise during a shuttle run test, such as workload, ventilatory response, or gas exchange during exercise, cannot be assessed, limiting the utility of these studies in understanding the underlying exercise limitation.
Cycle ergometry
Most exercise studies in children born preterm in the surfactant era used cycle ergometry, with some (10, 21, 31, 36) but not all (23–25, 30) studies showing a reduced peak V̇O2. Reductions in workload (10) and V̇O2/work (24, 31) were reported in the preterm population, even with normal peak V̇O2 (25, 30). These differences in workload and V̇O2/work may suggest differences in cardiovascular or peripheral muscle function underlie the reduced exercise capacity, as the V̇O2/work slope is related to cardiovascular and musculoskeletal responses to exercise (31, 37). The assessment of peak outcomes in a cycle ergometer test relies on the muscular endurance of the legs, in particular, the quadriceps. It is also plausible that the low workload and V̇O2/work relationship may be due to changes in the peripheral muscle mass (31).
Children born preterm have a persistent reduction in body mass with an overall reduction in bone, fat, and fat-free mass; however, there is no difference in the percentage of fat-free mass, suggesting that the overall reduction in body mass is proportional, even when accounting for height (13). This reduction in fat-free mass may lead to a reduction in peripheral muscle strength; indeed, Vardar-Yagli et al. (38) reported a reduction in peripheral muscle strength evaluated using a dynamometer in children born preterm. In particular, Vardar-Yagli et al. reported a significantly greater reduction in lower extremity muscle strength compared to upper body extremities. As exercise using a cycler ergometer requires lower extremity muscle strength, this reduced peripheral strength may make it more difficult for children born preterm to continue cycling at higher workloads, resulting in a reduced peak V̇O2 and V̇O2/work slope.
Treadmill
Preterm children born in the post-surfactant era typically have a normal peak V̇O2 when assessed using a treadmill-based exercise protocol (9, 22). A sensitivity analysis performed by Edwards et al. comparing metadata from different exercise testing modalities showed that treadmill testing was more likely to identify a difference between term and preterm groups than cycle ergometry (39). However, we note that the data that most heavily contributed to the differences observed were based on an abstract containing preliminary data (40), which, when submitted for full publication, showed no differences between the term and preterm groups (9). Exercise testing using a treadmill is advantageous because it mimics daily activities such as running and walking. The treadmill-based exercise involves the recruitment of a larger muscle mass compared to the predominately lower body recruitment in cycle-based exercise. This results in a higher peak V̇O2 and peak heart rate during a treadmill-based CPET than those obtained when using cycle ergometry in healthy subjects (41). Therefore, differences in muscle mass recruitment may explain the contrasting outcomes of the studies using cycle and treadmill protocols. However, treadmill exercise testing also relies on the child's cognitive ability to run to maximal exertion. Preterm children with muscle incoordination or gait impairment may terminate the exercise test early, resulting in a measurement bias favoring healthy children. In addition, preterm children unable to perform a peak exercise test are likelier to have worse lung function and more parentally reported symptoms (9). The literature contains no direct comparisons of treadmill and cycle ergometry feasibility in children born preterm, and testing modality is ultimately determined by equipment availability and the preference of the supervising team.
Oxygen update efficiency slope
Developmental delay and poor coordination are well-recognized in children following preterm birth. Accurate peak V̇O2 measurements can be difficult to achieve in this group as they are critically dependent on subject motivation and coordination and also on the skills of the observer. Baba et al. (42) proposed the oxygen uptake efficiency slope (OUES), a submaximal measurement of cardiopulmonary functional capacity. OUES is derived from the slope of V̇O2 plotted against the log of minute ventilation (V̇E), which is linear throughout testing,, and is independent of workload, enabling the assessment of cardiopulmonary exercise capacity even from submaximal tests. OUES has been validated against peak V̇O2 in children with congenital heart disease when assessed at the ventilatory threshold, 75% or 100% of peak V̇O2. Further, OUES has been proven to differentiate between disease groups (43, 44). The utility of OUES in a preterm population is largely unstudied. Therefore, it should be an area of future research, given the variability in reported outcomes, the difficulties testing in this population, and the possibility of healthy survivor bias. Hence, the wider use of OUES in the assessment of aerobic capacity in young children would allow for the generalization of results to a broader preterm population.
Ventilatory response to exercise
Exertional dyspnea in preterm-born individuals is attributed to an altered ventilatory response to exercise, which may be associated with decreased lung function. A growing body of evidence suggests that children born preterm mount an altered ventilatory response to exercise, characterized by a rapid breathing pattern (9, 10, 24, 25, 31). Some studies also report a shallow breathing pattern at peak exercise, identified by a reduced tidal volume (10, 21, 24, 31). Supporting these findings, our group (26) reported significantly higher breathing frequency to tidal volume ratios at peak exercise in school-aged children born very preterm with BPD. Two studies on children delivered extremely preterm (10, 21) showed a reduction in peak V̇E; however, studies on children delivered very preterm showed no alterations (9, 23, 31). The differences in results between children born extremely preterm and very preterm suggest that gestational age and lung development may play a role in altered ventilatory response.
Ventilatory efficiency during exercise as assessed by ventilatory equivalents for carbon dioxide and oxygen (V̇E/V̇CO2 and V̇E/V̇O2, respectively) independently predict hospitalizations and future exacerbations in other parenchymal lung diseases such as cystic fibrosis (16–19); ventilatory efficiency can be assessed using the V̇E/V̇CO2 slope. The effect of preterm birth on ventilatory efficiency is unresolved: two studies (21, 25) showed an increased V̇E/V̇CO2 slope, suggesting inefficient ventilation, while a further study showed no difference (31). In a study on very low birth weight (VLBW) children, conducted by Rideau Batista Novais et al. (25), the V̇E/V̇CO2 was elevated and associated with a reduction in end-tidal CO2, suggesting inefficient ventilation and hyperventilation during exercise (45). However, peak exercise ventilatory indices were similar between the VLBW and control groups. The authors hypothesized that this finding was due to either an altered CO2 setpoint or inspiratory muscle fatigue. However, the plausibility of a significant alteration in CO2 setpoint is unclear, given the normal peak exercise ventilatory outcomes. Respiratory muscle fatigue was suggested to be a more likely contributor to the altered ventilatory response, given increased inspiratory load for the same exercise intensity and, therefore, likely an increased susceptibility to fatigue (25). Supporting this hypothesis, Davidson et al. (46) found elevated sternocleidomastoid muscle activity in children born preterm, suggesting increased respiratory muscle activity at high-intensity exercise, which may lead to respiratory muscle fatigue. However, the mechanism(s) driving respiratory muscle fatigue remains largely unknown.
Expiratory flow limitation
One factor potentially contributing to altered ventilatory responses during exercise may be expiratory flow limitation (EFL). EFL is associated with an impaired ventilatory response to exercise in asthma, cystic fibrosis, and COPD (47–50). We identified two studies that assessed the prevalence and impact of EFL on exercise in preterm children born in the surfactant era (9, 21). Both studies showed that approximately half of all preterm children develop significant EFL during exercise compared to 25%–30% of term-born controls. Contrary to other obstructive lung diseases, the inspiratory capacity during exercise and the operational lung volumes were not altered in those born preterm, suggesting that gas trapping and airway collapse are not likely causes for EFL in this population. Instead, increased EFL without changes in operating lung volumes may be due to reduced pulmonary compliance and the consequent increased elastic load of breathing, respiratory muscle weakness, and altered respiratory mechanics. Preterm children may have respiratory muscle weakness, which may lead to an inability to overcome the increased work of breathing, leading to EFL; this increased work of breathing may also lead to dyspnea. However, there is no association between EFL and alterations in exercise capacity or ventilatory response to exercise (9, 21). In a 2018 study, we showed that the presence of EFL is associated with a lower gestational age and reduced FEV1/FVC (9). The influence of low FEV1/FVC is supported by the findings that EFL in healthy adults is explained mainly by alterations in lung and airway size or dysanapsis (smaller airway size relative to lung volume), which limits the capacity to generate the flows and volumes required during exercise (51). Given the disrupted lung growth and development associated with preterm birth, airway dysanapsis likely contributes to EFL in conjunction with respiratory muscle weakness and altered respiratory mechanics. Understanding the mechanisms underlying EFL and their contribution to exercise limitation will be key to clarifying the mechanisms of the altered ventilatory response and identifying potential therapeutic options for reducing respiratory morbidity.
Early V̇O2 recovery
Exertional dyspnea in preterm children is still poorly understood; there is no obvious correlation between exertional dyspnea with exercise outcomes despite reduced lung function (9, 10). Dyspnea is related to respiratory muscle strength and endurance in adults with congestive heart failure, and respiratory muscle strength is related to early recovery oxygen kinetics (52). Early recovery following maximal exercise is characterized by rapid payback of oxygen debt and resynthesis of phosphocreatine. This process depends on the transport and utilization of oxygen (53). In children with chronic chest diseases, such as cystic fibrosis and bronchiectasis, the V̇O2 recovery following maximal exercise is delayed (measured by the time to return to 50% of peak V̇O2) and is associated with disease severity. However, there is a large variability in the V̇O2 recovery rate (53). Recovery following a maximal exercise test depends not only on the size of the oxygen debt (larger debt, faster recovery) but also on the ability of the cardiovascular system to transport oxygen. Therefore, recovery may be a measure of cardiovascular fitness (54) or the ability of the skeletal muscles to take up the delivered oxygen due to alterations to structure or function (55). Currently, there is no evidence regarding V̇O2 recovery in children born preterm. However, assessment of early V̇O2 recovery may identify differences given the altered ventilatory response in preterm children (which may be related to altered respiratory muscle strength) and could help explain increased exertional symptoms.
Heart rate recovery
Following maximal exercise, the immediate heart rate recovery is mediated by the autonomic nervous system with activation of the parasympathetic nervous system via the reactivation of the vagal nervous system and the withdrawal of the sympathetic nervous system. Reduced vagal activity, which may delay heart rate recovery, is a predictor of all-cause mortality and is associated with metabolic risk factors in healthy children (56). The development of the autonomic nervous system occurs in the third trimester after the delivery of most preterm infants, making autonomic nervous system impairment plausible (57). To date, limited research has reported heart rate recovery following peak exercise in survivors of preterm birth. One study by Haraldsdottir et al. assessed 12 preterm patients who reported delayed heart rate recovery in adult survivors of preterm birth; however, it did not investigate the impact of neonatal variables (57). Another study by Huckstep et al. found that young adults who were born moderately preterm have lower peak V̇O2 and slower heart rate recovery following exercise compared to term controls. They concluded that impaired myocardial functional reserve may be a key factor underpinning these impairments (36). Given the known risks for metabolic disease in preterm children, altered heart rate recovery in this population may justify the evaluation of a cardiopulmonary rehabilitation program to help modify these risks and reduce exertional dyspnea. This has been successful in other childhood diseases; cardiac rehabilitation was shown to improve heart rate recovery in children with complex congenital heart disease (58). The role of cardiopulmonary rehabilitation programs in improving heart rate recovery and other exercise outcomes in those born preterm is yet to be fully realized; however, it should be a focus of future robust randomized controlled trials.
Conclusion
Children born preterm have disrupted lung growth and development, which results in significant respiratory symptoms, structural changes to the lung, and a reduction in lung function. During exercise, a significantly altered ventilatory response is evident; however, the underlying mechanisms and their clinical significance remain unclear. Associations between resting assessments of lung health (function, structure, and symptoms) and exercise limitation are poorly understood and cannot accurately predict exercise limitation. Due to the heterogeneity of participants, treatments, and exercise protocols, there are variable reports in the literature about the nature and extent of exercise limitation in those born preterm.
CPET assesses interactions between the metabolic, respiratory, cardiovascular, and musculoskeletal systems, and by utilizing this tool to its full potential, the pathophysiological consequences of preterm birth can be further investigated. Enhanced knowledge of the pathophysiology of impaired lung function in childhood will open new avenues for interventions to prevent further deterioration in lung function throughout childhood.
Author contributions
CO’D: drafted the initial manuscript. CO’D, ES, and MB: contributed to drafting the manuscript hereafter. All authors contributed to the article and approved the submitted version.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
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References
1. Blencowe H, Cousens S, Chou D, Oestergaard M, Say L, Moller AB, et al. Born too soon: the global epidemiology of 15 million preterm births. Reprod Health. (2013) 10(Suppl 1):S2. doi: 10.1186/1742-4755-10-S1-S2
2. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. (2001) 163(7):1723–9. doi: 10.1164/ajrccm.163.7.2011060
3. Coalson JJ. Pathology of bronchopulmonary dysplasia. Semin Perinatol. (2006) 30(4):179–84. doi: 10.1053/j.semperi.2006.05.004
4. Simpson SJ, Logie KM, O'Dea CA, Banton GL, Murray C, Wilson AC, et al. Altered lung structure and function in mid-childhood survivors of very preterm birth. Thorax. (2017) 72(8):702–11. doi: 10.1136/thoraxjnl-2016-208985
5. Doyle LW, Andersson S, Bush A, Cheong JLY, Clemm H, Evensen KAI, et al. Expiratory airflow in late adolescence and early adulthood in individuals born very preterm or with very low birthweight compared with controls born at term or with normal birthweight: a meta-analysis of individual participant data. Lancet Respir Med. (2019) 7(8):677–86. doi: 10.1016/s2213-2600(18)30530-7
6. Yang J, Kingsford RA, Horwood J, Epton MJ, Swanney MP, Stanton J, et al. Lung function of adults born at very low birth weight. Pediatrics. (2020) 145(2):e20192359. doi: 10.1542/peds.2019-2359
7. Bui DS, Perret JL, Walters EH, Lodge CJ, Bowatte G, Hamilton GS, et al. Association between very to moderate preterm births, lung function deficits, and COPD at age 53 years: analysis of a prospective cohort study. Lancet Respir Med. (2022) 10(5):478–84. doi: 10.1016/s2213-2600(21)00508-7
8. Siebel AL, Carey AL, Kingwell BA. Can exercise training rescue the adverse cardiometabolic effects of low birth weight and prematurity? Clin Exp Pharmacol Physiol. (2012) 39(11):944–57. doi: 10.1111/j.1440-1681.2012.05732.x
9. O’Dea CA, Logie K, Maiorana A, Wilson AC, Pillow JJ, Banton GL, et al. Increased prevalence of expiratory flow limitation during exercise in children with bronchopulmonary dysplasia. ERJ Open Res. (2018) 4(4):00048-2018. doi: 10.1183/23120541.00048-2018
10. Welsh L, Kirkby J, Lum S, Odendaal D, Marlow N, Derrick G, et al. The epicure study: maximal exercise and physical activity in school children born extremely preterm. Thorax. (2010) 65(2):165–72. doi: 10.1136/thx.2008.107474
11. American Thoracic Society, American College of Chest Physicians. ATS/ACCP statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. (2003) 167(2):211–77. doi: 10.1164/rccm.167.2.211
12. Bonamy AK, Bendito A, Martin H, Andolf E, Sedin G, Norman M. Preterm birth contributes to increased vascular resistance and higher blood pressure in adolescent girls. Pediatr Res. (2005) 58(5):845–9. doi: 10.1203/01.PDR.0000181373.29290.80
13. Wang D, Vandermeulen J, Atkinson SA. Early life factors predict abnormal growth and bone accretion at prepuberty in former premature infants with/without neonatal dexamethasone exposure. Pediatr Res. (2007) 61(1):111–6. doi: 10.1203/01.pdr.0000250206.79628.66
14. Kajantie E, Hovi P. Is very preterm birth a risk factor for adult cardiometabolic disease? Semin Fetal Neonatal Med. (2014) 19(2):112–7. doi: 10.1016/j.siny.2013.11.006
15. Blair SN, Kohl HW 3rd, Paffenbarger RS Jr., Clark DG, Cooper KH, Gibbons LW. Physical fitness and all-cause mortality. A prospective study of healthy men and women. JAMA (1989) 262(17):2395–401. doi: 10.1001/jama.262.17.2395
16. Hebestreit H, Hulzebos EHJ, Schneiderman JE, Karila C, Boas SR, Kriemler S, et al. Cardiopulmonary exercise testing provides additional prognostic information in cystic fibrosis. Am J Respir Crit Care Med. (2019) 199(8):987–95. doi: 10.1164/rccm.201806-1110OC
17. Hulzebos EHJ, Bomhof-Roordink H, van de Weert-van Leeuwen PB, Twisk JWR, Arets HGM, van der Ent CK, et al. Prediction of mortality in adolescents with cystic fibrosis. Med Sci Sports Exerc. (2014) 46(11):2047–52. doi: 10.1249/mss.0000000000000344
18. Nixon PA, Orenstein DM, Kelsey SF, Doershuk CF. The prognostic value of exercise testing in patients with cystic fibrosis. N Engl J Med. (1992) 327(25):1785–8. doi: 10.1056/NEJM199212173272504
19. Pastré J, Prévotat A, Tardif C, Langlois C, Duhamel A, Wallaert B. Determinants of exercise capacity in cystic fibrosis patients with mild-to-moderate lung disease. BMC Pulm Med. (2014) 14(1):74. doi: 10.1186/1471-2466-14-74
20. Smith L, van Asperen P, McKay K, Selvadurai H, Fitzgerald D. Reduced exercise capacity in children born very preterm. Paediatrics. (2008) 122(2):e287–93. doi: 10.1542/peds.2007-3657
21. MacLean JE, DeHaan K, Fuhr D, Hariharan S, Kamstra B, Hendson L, et al. Altered breathing mechanics and ventilatory response during exercise in children born extremely preterm. Thorax. (2016) 71(11):1012–9. doi: 10.1136/thoraxjnl-2015-207736
22. Clemm H, Roksund O, Thorsen E, Eide GE, Markestad T, Halvorsen T. Aerobic capacity and exercise performance in young people born extremely preterm. Pediatrics. (2012) 129(1):e97–105. doi: 10.1542/peds.2011-0326
23. Joshi S, Powell T, Watkins WJ, Drayton M, Williams EM, Kotecha S. Exercise-induced bronchoconstriction in school-aged children who had chronic lung disease in infancy. J Pediatr. (2013) 162(4):813–8.e1. doi: 10.1016/j.jpeds.2012.09.040
24. Kriemler S, Keller H, Saigal S, Bar-Or O. Aerobic and lung performance in premature children with and without chronic lung disease of prematurity. Clin J Sport Med. (2005) 15(5):349–55. doi: 10.1097/01.jsm.0000180023.44889.dd
25. Rideau Batista Novais A, Matecki S, Jaussent A, Picot MC, Amedro P, Guillaumont S, et al. Hyperventilation during exercise in very low birth weight school-age children may implicate inspiratory muscle weakness. J Pediatr. (2012) 160(3):415–20.e1. doi: 10.1016/j.jpeds.2011.09.014
26. O'Dea CA, Logie K, Wilson AC, Pillow JJ, Murray C, Banton G, et al. Lung abnormalities do not influence aerobic capacity in school children born preterm. Eur J Appl Physiol. (2021) 121(2):489–98. doi: 10.1007/s00421-020-04530-2
27. Hochwald O, Bentur L, Haddad Y, Hanna M, Zucker-Toledano M, Mainzer G, et al. Cardiopulmonary exercise testing in childhood in late preterms: comparison to early preterms and term-born controls. J Pers Med. (2022) 12(10):1547. doi: 10.3390/jpm12101547
28. Clemm HH, Vollsaeter M, Roksund OD, Markestad T, Halvorsen T. Adolescents who were born extremely preterm demonstrate modest decreases in exercise capacity. Acta Paediatr. (2015) 104(11):1174–81. doi: 10.1111/apa.13080
29. Dodd JD, Barry SC, Barry RB, Gallagher CG, Skehan SJ, Masterson JB. Thin-section CT in patients with cystic fibrosis: correlation with peak exercise capacity and body mass index. Radiology. (2006) 240(1):236–45. doi: 10.1148/radiol.2401050502
30. Kaplan E, Bar-Yishay E, Prais D, Klinger G, Mei-Zahav M, Mussaffi H, et al. Encouraging pulmonary outcome for surviving, neurologically intact, extremely premature infants in the postsurfactant era. Chest. (2012) 142(3):725–33. doi: 10.1378/chest.11-1562
31. Pianosi PT, Fisk M. Cardiopulmonary exercise performance in prematurely born children. Pediatr Res. (2000) 47(5):653–8. doi: 10.1203/00006450-200005000-00016
32. Danks M, Burns YR, Gibbons K, Gray PH, O’Callaghan MJ, Poulsen L, et al. Fitness limitations in non-disabled extremely low birthweight adolescents. J Paediatr Child Health. (2013) 49(7):548–53. doi: 10.1111/jpc.12281
33. Tsopanoglou SP, Davidson J, Goulart AL, Barros MC, dos Santos AM. Functional capacity during exercise in very-low-birth-weight premature children. Pediatr Pulmonol. (2014) 49(1):91–8. doi: 10.1002/ppul.22754
34. Burns YR, Danks M, O'Callaghan MJ, Gray PH, Cooper D, Poulsen L, et al. Motor coordination difficulties and physical fitness of extremely-low-birthweight children. Dev Med Child Neurol. (2009) 51(2):136–42. doi: 10.1111/j.1469-8749.2008.03118.x
35. Hurst JR, Beckmann J, Ni Y, Bolton CE, McEniery CM, Cockcroft JR, et al. Respiratory and cardiovascular outcomes in survivors of extremely preterm birth at 19 years. Am J Respir Crit Care Med. (2020) 202(3):422–32. doi: 10.1164/rccm.202001-0016OC
36. Huckstep OJ, Burchert H, Williamson W, Telles F, Tan CMJ, Bertagnolli M, et al. Impaired myocardial reserve underlies reduced exercise capacity and heart rate recovery in preterm-born young adults. Eur Heart J Cardiovasc Imaging. (2021) 22(5):572–80. doi: 10.1093/ehjci/jeaa060
37. Groen WG, Hulzebos HJ, Helders PJ, Takken T. Oxygen uptake to work rate slope in children with a heart, lung or muscle disease. Int J Sports Med. (2010) 31(3):202–6. doi: 10.1055/s-0029-1243644
38. Vardar-Yagli N, Inal-Ince D, Saglam M, Arikan H, Savci S, Calik-Kutukcu E, et al. Pulmonary and extrapulmonary features in bronchopulmonary dysplasia: a comparison with healthy children. J Phys Ther Sci. (2015) 27(6):1761–5. doi: 10.1589/jpts.27.1761
39. Edwards MO, Kotecha SJ, Lowe J, Watkins WJ, Henderson AJ, Kotecha S. Effect of preterm birth on exercise capacity: a systematic review and meta-analysis. Pediatr Pulmonol. (2015) 50(3):293–301. doi: 10.1002/ppul.23117
40. O’Dea C, Logie K, Wilson A, Maiorana A, Pillow J, Hall G. Children with bronchopulmonary dysplasia have altered ventilatory response to exercise. Respirology. (2011) 16(Supplement S1):1–4. doi: 10.1111/j.1440-1843.2011.01934.x
41. Keren G, Magazanik A, Epstein Y. A comparison of various methods for the determination of VO2max. Eur J Appl Physiol Occup Physiol. (1980) 45(2–3):117–24. doi: 10.1007/bf00421319
42. Baba R, Nagashima M, Goto M, Nagano Y, Yokota M, Tauchi N, et al. Oxygen uptake efficiency slope: a new index of cardiorespiratory functional reserve derived from the relation between oxygen uptake and minute ventilation during incremental exercise. J Am Coll Cardiol. (1996) 28(6):1567–72. doi: 10.1016/s0735-1097(96)00412-3
43. Bongers BC, Hulzebos HJ, Blank AC, van Brussel M, Takken T. The oxygen uptake efficiency slope in children with congenital heart disease: construct and group validity. Eur J Cardiovasc Prev Rehabil. (2011) 18(3):384–92. doi: 10.1177/1741826710389390
44. Davies LC, Wensel R, Georgiadou P, Cicoira M, Coats AJ, Piepoli MF, et al. Enhanced prognostic value from cardiopulmonary exercise testing in chronic heart failure by non-linear analysis: oxygen uptake efficiency slope. Eur Heart J. (2006) 27(6):684–90. doi: 10.1093/eurheartj/ehi672
45. Wasserman K, Hansen J, Sue D, Stringer W, Sietsema K, Sun XG, Whipp B. Chapter 4: Measurements during integrative cardiopulomanry exercise testing. Section in: Principles of exercise testing and interpretation: including pathophysiology and clinical applications. 5th ed. London: Lippincott Williams & Wilkins (2012). p. 71–106.
46. Davidson J, Tsopanoglou SP, Dourado VZ, Nunes Dos Santos AM, Goulart AL, Amorim CF, et al. Pattern of respiratory muscle activity during exercise tests in children born prematurely. J Bodyw Mov Ther. (2020) 24(3):78–83. doi: 10.1016/j.jbmt.2020.02.003
47. Regnis JA, Alison JA, Henke KG, Donnelly PM, Bye PT. Changes in end-expiratory lung volume during exercise in cystic fibrosis relate to severity of lung disease. Am Rev Respir Dis (1991) 144(3 Pt 1):507–12. doi: 10.1164/ajrccm/144.3_Pt_1.507
48. Laveneziana P, Webb KA, Ora J, Wadell K, O'Donnell DE Evolution of dyspnea during exercise in chronic obstructive pulmonary disease: impact of critical volume constraints. Am J Respir Crit Care Med. (2011) 184(12):1367–73. doi: 10.1164/rccm.201106-1128OC
49. O’Donnell DE, Laveneziana P. The clinical importance of dynamic lung hyperinflation in COPD. COPD. (2006) 3(4):219–32. doi: 10.1080/15412550600977478
50. Lougheed MD, Fisher T, O'Donnell DE. Dynamic hyperinflation during bronchoconstriction in asthma: implications for symptom perception. Chest. (2006) 130(4):1072–81. doi: 10.1378/chest.130.4.1072
51. Smith JR, Rosenkranz SK, Harms CA. Dysanapsis ratio as a predictor for expiratory flow limitation. Respir Physiol Neurobiol. (2014) 198:25–31. doi: 10.1016/j.resp.2014.04.001
52. Nanas S, Nanas J, Kassiotis C, Alexopoulos G, Samakovli A, Kanakakis J, et al. Respiratory muscles performance is related to oxygen kinetics during maximal exercise and early recovery in patients with congestive heart failure. Circulation. (1999) 100(5):503–8. doi: 10.1161/01.cir.100.5.503
53. Stevens D, Oades PJ, Armstrong N, Williams CA. Early oxygen uptake recovery following exercise testing in children with chronic chest diseases. Pediatr Pulmonol. (2009) 44(5):480–8. doi: 10.1002/ppul.21024
54. Singh TP, Alexander ME, Gauvreau K, Curran T, Rhodes Y, Rhodes J. Recovery of oxygen consumption after maximal exercise in children. Med Sci Sports Exerc. (2011) 43(4):555–9. doi: 10.1249/MSS.0b013e3181f683b8
55. Nanas S, Sakellariou D, Kapsimalakou S, Dimopoulos S, Tassiou A, Tasoulis A, et al. Heart rate recovery and oxygen kinetics after exercise in obstructive sleep apnea syndrome. Clin Cardiol. (2010) 33(1):46–51. doi: 10.1002/clc.20707
56. Laguna M, Aznar S, Lara MT, Lucia A, Ruiz JR. Heart rate recovery is associated with obesity traits and related cardiometabolic risk factors in children and adolescents. Nutr Metab Cardiovasc Dis. (2013) 23(10):995–1001. doi: 10.1016/j.numecd.2012.10.002
57. Haraldsdottir K, Watson AM, Beshish AG, Pegelow DF, Palta M, Tetri LH, et al. Heart rate recovery after maximal exercise is impaired in healthy young adults born preterm. Eur J Appl Physiol. (2019) 119(4):857–66. doi: 10.1007/s00421-019-04075-z
Keywords: exercise and lung disease, bronchopulmonary dysplasia, pediatric lung disease, lung physiology, pediatric exercise physiology
Citation: O’Dea CA, Beaven ML, Wilson AC, Smith EF, Maiorana A and Simpson SJ (2023) Preterm birth and exercise capacity: what do we currently know?. Front. Pediatr. 11:1222731. doi: 10.3389/fped.2023.1222731
Received: 15 May 2023; Accepted: 12 September 2023;
Published: 6 October 2023.
Edited by:
Theo Dassios, King’s College Hospital NHS Foundation Trust, United KingdomReviewed by:
Anne Greenough, King’s College London, United KingdomSotirios Fouzas, University of Patras, Greece
© 2023 O'Dea, Beaven, Wilson, Smith, Maiorana and Simpson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Christopher A. O’Dea Chris.odea@health.wa.gov.au