Pulmonary morbidity in bronchopulmonary dysplasia survivors: a recommendation for long-term follow-up

Pulmonary morbidity in bronchopulmonary dysplasia survivors: a recommendation for long-term follow-up | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 22 April 2025 V1 Latest version Share on Pulmonary morbidity in bronchopulmonary dysplasia survivors: a recommendation for long-term follow-up Authors : Jarno Steenhorst J , Alain Dubois , Lidewij Visser S , Arnold Duinisveld J , Alexander Hirsch , Irwin Reiss , Willem Helbing H , Daphne Merkus , and Lieke Kamphuis S [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174530722.26003823/v1 190 views 73 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: In the western world, 30-40% of very preterm born infants develop bronchopulmonary dysplasia (BPD), a severe and common complication of preterm birth, with a potential long lasting impact on cardiopulmonary health. Objective: To investigate long term pulmonary morbidity in preterm born young adults with and without BPD, compared to at term born young adults. Methods: 20 preterm born young adults BPD ( gestational age (GA), 27 [26-28] weeks) and 20 without BPD (GA age 28 [27-29] weeks (median[IQR])) were prospectively compared to at term born young adults (GA 39 [38-40] weeks). Participants were subjected to spirometry, body plethysmography, cardiopulmonary exercise testing and quality of life status. Results: Forced vital capacity in 1 second (FEV1) was significantly reduced in BPD participants compared to preterm born participants without BPD (mean±SD Z-score: -1.73±0.79 vs. -0.41±0.70, p<0.001) and compared to at term born participants (-0.49±1.00; p<0.001). 70% of the BPD participants showed an airflow obstruction. In cardiopulmonary exercise testing, BPD participants had lower peak oxygen consumption compared to at term born participants (91±18 vs. 106±17% of predicted, p=0.01). A slight decrease in percieved physical functioning was reported in BPD participants compared to at term born participants (95 [83-100] vs 100 [95; 100]). Conclusions: BPD participants show a distinct, obstructive lung pattern without overt daily life complaints compared to preterm born participants without BPD and at term born young adults, and might be at increased risk for chronic obstructive pulmonary disease later in life. Title : Pulmonary morbidity in bronchopulmonary dysplasia survivors: a recommendation for long-term follow-up Authors: Jarno J Steenhorst 1,2,3 , Alain Dubois 4,5 , Lidewij S Visser 4 , Arnold J Duinisveld 4 , Alexander Hirsch 1,3 , Irwin KM Reiss 6 , Willem H Helbing 2,3 , Daphne Merkus 1,7 , Lieke S Kamphuis 4* . Affiliations: 1 Department of Cardiology, Cardiovascular Institute, Thorax center, Erasmus MC, Rotterdam, The Netherlands. 2 Department of Pediatrics, Division of Pediatric Cardiology, Erasmus MC, Rotterdam, The Netherlands. 3 Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands. 4 Department of Pulmonology, Erasmus MC, Rotterdam, The Netherlands. 5 Department of Respiratory Medicine, Admiraal De Ruyter hospital, Goes, The Netherlands. 6 Department of Pediatrics, Division of Neonatology, Erasmus MC, Rotterdam, The Netherlands. 7 Institute for Surgical Research, Walter-Brendel Centre of Experimental Medicine, LMU Munich, University Hospital, Munich, Germany. 8 German Center for Cardiovascular Research (DZHK), Munich Heart Alliance (MHA), Partner Site Munich; 9 Interfaculty Center for Endocrine and Cardiovascular Disease Network Modelling and Clinical Transfer (ICONLMU), LMU Munich, Munich, Germany Funding: Thorax foundation project number 22109, Erasmus MC Sophia Foundation S12-13, and participating departments of Erasmus Medical Center Corresponding author: LS Kamphuis, MD PhD, Department of Pulmonology, room Rg-430, Erasmus Medical University Center PO Box 2040, 3000 CA Rotterdam The Netherlands, Phone: 0031650031794, Email: [email protected] Author contributions: JS, AH, IR, LV, WH, DM, LK conceptualized and designed the study. JS, AD, AJD, LV, LK performed and assessed individual results, JS, LK drafted the initial manuscript. All authors have read and revised the final manuscript and approved it for publication. Conflicts of interests: None to declare. Key words: BPD, prematurity, long-term, young adult, obstructive disease Running head: Obstructive disease in bronchopulmonary dysplasia. Background: In the western world, 30-40% of very preterm born infants develop bronchopulmonary dysplasia (BPD), a severe and common complication of preterm birth, with a potential long lasting impact on cardiopulmonary health. Objective: To investigate long term pulmonary morbidity in preterm born young adults with and without BPD, compared to at term born young adults. Methods: 20 preterm born young adults BPD ( gestational age (GA), 27 [26-28] weeks) and 20 without BPD (GA age 28 [27-29] weeks (median[IQR])), selected according to the NICHD 2001 criteria, were prospectively compared to at term born young adults (GA 39 [38-40] weeks). Participants were subjected to spirometry, body plethysmography, cardiopulmonary exercise testing and quality of life status. Results: Forced vital capacity in 1 second (FEV1) was significantly reduced in BPD participants compared to preterm born participants without BPD (mean±SD Z-score: -1.73±0.79 vs. -0.41±0.70, p<0.001) and compared to at term born participants (-0.49±1.00; p<0.001). 70% of the BPD participants showed an airflow obstruction. In cardiopulmonary exercise testing, BPD participants had lower peak oxygen consumption compared to at term born participants (91±18 vs. 106±17% of predicted, p=0.01). A slight decrease in physical functioning was reported in BPD participants compared to at term born participants (95 [83-100] vs 100 [95; 100]). Conclusions: BPD participants show a distinct, obstructive lung pattern without overt daily life complaints compared to preterm born participants without BPD and at term born young adults, and might be at increased risk for chronic obstructive pulmonary disease later in life. Introduction Bronchopulmonary dysplasia (BPD) is a multifactorial lung disease of prematurity characterized by an increased risk of pulmonary infections during childhood, accompanied by decreased lung function and exercise capacity 12, . In very premature born infants, defined as those born below 32 weeks of gestational age, 30-40% develop BPD 34, . Advances in treatment modalities, including administration of surfactant and improved ventilation settings in the nineties resulted in increased survival rates of up to 75% 56, . It was later recognized that these interventions led to an arrest in lung development, ‘new’ BPD 178, . Over the past decades, BPD incidence remained consistent, effectively leading to a steady increase in adult BPD patients 2 . Data on adult preterm survivors with ‘new’ BPD is scarce. The oldest population of this group of patients is around 30 years old, while this first generation new BPD is often without regular pulmonary follow-up. The 2020 guidelines of the European Respiratory Society on long-term management of patients with BPD state that monitoring pulmonary morbidity of all former BPD patients is needed 9 . In other pulmonary diseases, the range of puberty until young adulthood is an critical period in disease management with low therapy compliance and high probability of loss-to-follow up 10 . This could lead to increased chances of hospitalisation and increased healthcare costs later in life, which could also apply for BPD patients. Therefore, understanding of pulmonary morbidity in this population is critical to determine timing of follow-up and increase outcomes. The aim of this study was to evaluate long-term morbidities in adults born preterm with and without BPD, by combining spirometry, body plethysmography, cardiopulmonary exercise testing and quality of life (by the short form 36 questionnaire). Materials and methods Participants In this prospective cohort study, participants were recruited as published before, and mentioned in the supplement 11 . BPD was diagnosed based on the hospital records and defined as: ≥28 consecutive days of oxygen therapy since birth 1 . All participants gave written informed consent. The study protocol was approved by the medical ethics board of Erasmus Medical Center, Rotterdam (MEC2016-427). Demographics and study design Perinatal and demographic characteristics were retrieved from medical records and participants themselves. Participants underwent pulmonary function tests (PFT), including spirometry, bodyplethysmography, lung diffusion testing and cardiopulmonary exercise testing (CPET). CPET was considered maximal if participants reached a respiratory exchange ratio of 1.05 and/or 90% of predicted maximal heart rate 12 . After a resting period (>30 min), participants performed a second spirometry and bodyplethysmography, followed by 400 ug of inhalation of salbutamol to test reversibility during the third spirometry and bodyplethysmography. CPET and spirometry were performed according to the American Thoracic Society/European Respiratory Society guidelines 13-15 . Participants using inhalers had been instructed to stop short-acting B2-agonists 8 hours before and long-acting B2-agonists 24 hours before assessment. Results of PFT (L.K. or L.V.) and CPET (A.D.) were reviewed by a trained pulmonologist, irrespective of knowledge of group. If a participant showed an aberrant PFT, their general practitioner was contacted to inform that the participant was eligible for a consultation with a pulmonologist. Statistical analyses Normally distributed data are expressed as mean±standard deviation and evaluated using a one-way ANOVA. Non-normal distributed data are expressed as median (25 th ; 75 th interquartile) and evaluated using Kruskal-Wallace test. Data expressed as absolute values (%) were evaluated using a Fisher’s exact test. Analyses were performed in SPSS v 28 (IBM, Chicago, IL). Results Participants As published before, all participants (33 (55%) female, aged 23±2 years) completed the PFT and CPET 11 . Eight at term born siblings of preterm born participants were included in the at term group. Age, sex, body mass index, smoking habits, asthma diagnosis, use of inhalation medication and activity/exercise time were not significantly different between groups (Table 1). In the preterm born groups, there were no significant differences in gestational age, birth weight, prenatal celestone or postnatal surfactant admission. Maximum exercise capacity, expressed as maximum oxygen consumption (VO 2max ), was significantly lower in BPD participants compared to at term born participants, while no differences were found between preterm participants without BPD compared to the other groups (Table 2). A similar pattern was seen in oxygen pulse and ventilation at peak exercise. FEV1 and Tiffeneau index were significantly lower in BPD participants compared to preterm born participants without BPD or at term born participants, indicating obstructive lung function in the BPD group (Figure 1). An airflow obstruction was seen in 14 (70%) of the BPD participants compared to 2 (10%) of the preterm without BPD participants (p<.001). In 6 (43%) BPD participants with airflow obstruction, it was considered reversible compared to a reversible airflow obstruction in both preterm participants (100%) without BPD. Consistent with FEV1 data, body plethysmography revealed increased airway resistance in preterm born young adults with BPD, compared to preterm born young adults without BPD and at term born young adults (Supplemental table E2). Residual volume and residual volume/total lung capacity was slightly increased in participants with BPD compared to preterm participants without BPD, but not compared to at term born young adults. The use of salbutamol did not result in differences between groups in RV, RV/TLC or the amount of individuals showing significant reduction of airway resistance (>50%) (Supplemental table E2). Post-exercise spirometry and body plethysmography were not significantly different compared to baseline (data not shown). Table 4 depicts self-reported quality of life status of all participants. No differences were found in complaints by history at start of the study. Using the Short Form-36 questionnaire, preterm born young adults without BPD reported no limitations in physical and emotional well-being compared to at term born young adults. BPD participants reported slightly less physical well-being compared to preterm born young adults without BPD, and trending towards a decrease compared to at term born young adults. Exploratory data revealed a positive association of FEV1 z-score with birth weight and a negative correlation with oxygen dependency, while no association was found with gestational age preterm born young adults with/without BPD (Figure 2). Multivariate analysis showed oxygen dependency as independent predictor for FEV1 z-score (β with 95% confidence interval: -0.017, -0.027; -0.007, adjusted p-value= 0.002). Discussion This study evaluated the lung condition of very preterm born young adults with and without BPD compared to at term born young adults, all born in the post-surfactant era, using PFT, body plethysmography, CPET and a SF-36 questionnaire. Main results were: I) 70% of BPD participants showed airflow obstruction of which 43% was reversible compared to 10% of preterm born participants without BPD who all had a reversible airflow obstruction. II) Maximal oxygen consumption at peak exercise during CPET is decreased in BPD participants compared to at term born participants, mostly due to male participants with BPD. In male BPD participants, maximal oxygen consumption showed a decreasing trend compared to male preterm born participants without BPD. III) Pulmonary parameters as measured during CPET were not significantly decreased in BPD participants compared to the other groups. IV) BPD or preterm born participants without BPD did not report limitations in daily life, and reported a slight decrease in perceived physical functioning using the SF-36 questionnaire. Exploratory data showed: V) Postnatal days of oxygen dependency is inversely associated with FEV1 and FEV1/VC, while birth weight is positively associated with FEV1. No association between gestational age and FEV1 was found. The developmental lung disease BPD remains the most prevalent comorbidity of extreme prematurity 2 . BPD is associated with increased mortality rates, pulmonary hypertension and prolonged hospitalization in the early weeks of life 81617, . To the best of our knowledge, long term follow-up of BPD adults is not commonly performed. As recognized by the European respiratory society, long term follow-up into adulthood is considered imperative 9 . The trajectory of lung function of healthy individuals increases during childhood, peaks in early adulthood, then declining with age 18 . Lower peak values, as shown in our BPD cohort, and/or rapid decline in lung function is not only associated with increased incidence of pulmonary disease (such as COPD), but also a marker for a decline in general health, while increased peak values and moderate decline is considered healthy aging 19 . This study investigated participants between 18-27 years of age and showed clear obstructive lung disease in young adults with BPD, evidenced by PFT and body plethysmography, while no signs of restriction were found. In our study, preterm born young adults without BPD showed obstructive lung disease in 10%. Earlier studies however, showed higher obstructive airflow rates in PFTs in preterm born young adults without BPD 2021, . This could be explained by differences in criteria for BPD diagnosis, as the definition of BPD changed during the last decades. This complicates the interpretation of long-term morbidity of adults with BPD. Our study used criteria for new BPD was formulated by the National Institute of Child and Human Development (NICHD) in 2001, as 28 days of oxygen dependency, with grading at 36 weeks of post-menstrual age (PMA) 1 . In 2018, the NICHD opted to reformulate the definition to oxygen dependency at 36 weeks of postmenstrual age, which was refined by Jensen et al using the NICHD Neonatal Research Network (NRN) study in 2019, updating the grading system 2223, . This could lead to subjects qualified as (mild) BPD in the NICHD 2001 criteria, but as no BPD in the NRN criteria, when they were off respiratory support at 36 weeks of post menstrual age after 28 days of oxygen support. Both earlier studies used the NRN 2019 criteria 1 . Effectively, this could result in an increase in obstructive disease seen in the preterm born group without BPD. Exploratory analysis in our study showed negative association of FEV1 and postnatal oxygen dependency, supporting a gradual decrease according to respiratory support in the early weeks of life. Criteria of BPD diagnosis are validated in different time-frames, and therefore changed as a result of improvements in neonatal care over the last decades. It remains the question if infants born in earlier time periods (1991-2001) should comply to the former criteria (NICHD 2001) in interpretation of long term morbidity and follow-up of BPD, instead of using criteria validated in later time-frames. Recently, COPD due to abnormal development (COPD-D) was added to the COPD nomenclature 24 . The very preterm/BPD population might be at increased risk of developing this type of COPD, as peak lung function is lower and might be more vulnerable to rapid decline 19 . Adults born very preterm in de pre-surfactant era showed increased risk of developing COPD at 53 years of age, and have been shown to follow a similar, but below normal trajectory until 35 years of age compared to at term born adults 2526, . The trajectory of post-surfactant era preterms remains to be determined. In order to monitor progression COPD-D (due to abnormal lung development), it is important to consider the natural course of lung function and to evaluate risk factors for poor outcome in this population and ultimately, develop therapies to prevent early COPD-D in BPD and preterm born adults 2728, . In our study, exercise capacity in terms of peak VO 2 was lower in BPD participants (NICHD 2001 criteria) compared to at term born controls, but not compared to preterm born participants without BPD. Even though the current literature predominantly investigated participants born in the pre-surfactant era or during childhood, these results seem comparable 29-32 . Exercise capacity is consistently lower compared to at term born participants, but rarely decreased to clinically relevant levels. Similarly we found a slight decrease in perceived physical functioning in BPD participants, as assessed by SF-36 questionnaire. As VO 2 is a result of cardiac, pulmonary and muscle physiology, reserve and compensatory mechanisms may lead to only slight reductions in exercise capacity and therefore in minimal differences in disease perception of this population. The lack of disease perception in BPD participants could also be explained by habituation, as young adults with BPD have been limited since birth. This phenomenon also seen in children with asthma 33 . Although not significant, median self-reported exercise per week was lower in BPD participants compared to preterm participants without BPD or at term born participants. It remains to be investigated if less exercise is the cause for lower maximal exercise capacity or a consequence of the prematurity. In exploratory analyses, earlier findings on the positive association between birth weight and FEV1 were confirmed in our study 34 . Need for prolonged oxygen was inversely associated with FEV1 in preterm born young adults. Both factors indicate a continuous influence on airflow limitation, instead of dichotomous cut-off. Using perinatal factors such as birth weight and oxygen dependency, combined with spirometry during young adulthood (at physiological peak lung function) could be a viable option in the risk stratification and follow-up of preterm born adults. Follow-up into adulthood None of the BPD participants of this study was under active consultation or follow-up of a pulmonologist, possibly explained by the low self-reported complains and only slight decrease in perceived physical functioning. However, 70% showed airflow obstruction. Underdiagnoses and delayed treatment of (early signs of) pulmonary disease could eventually lead to increased costs for society 35 . This study shows that using NICHD 2001 criteria in a population born between 1993 and 2001 could be a valuable tool to stratify in long term follow-up of preterm born adults. When more recent BPD criteria are used, such as the NRN 2019 criteria, preterm born young adults without BPD born in this timeframe should not be neglected in the follow-up. Furthermore, this study showed that lack of perceived limitations do not reflect normal lung function in this population, indicating that an active follow-up is implied. This study highlights the importance of the definition used for diagnosing BPD – considering time frame of birth - when determining the screening recommendations in young adults populations. Large, population based studies should be conducted to define if diagnosis of BPD should compel to birth-era and if active follow-up remains cost-efficient. Strengths and weaknesses This observational study thoroughly evaluated one of the oldest very preterm born populations in the post-surfactant era, combining exercise testing with PFT and body-plethysmography. Furthermore, siblings were included as controls, to reduce possible socio-economic and genetic selection bias. However, we excluded participants with neurocognitive impairments that prevented use of CPET, which could lead to selection bias towards more healthy, cooperative participants. We included relatively low number of participants, while this was sufficient to determine differences compared to BPD participants, differences between preterm born young adults without BPD and at term born participants might be more subtle and prone to type II error. Conclusions Preterm born young adults with BPD, born in the post-surfactant era, have a distinct, obstructive lung disease. In our study, preterm born young adults without BPD did not show aberrant lung function, when subjected to the NICHD 2001 criteria. Exploratory data revealed an inverse correlation of FEV1 with postnatal oxygen dependency. Follow-up of BPD patients might be of additional value in determining risk profiles for adult lung disease in very preterm born young adults born between 1993 and 2001. Population based studies in preterm born adults with and without BPD should evaluate the progression of aberrant lung function into adulthood, in order to develop preventive and follow-up programs for adults born very preterm. Acknowledgements: We thank Frans Mertens, Léan de Ruiter, Monique Wapenaar and Karin Lammering for their excellent technical support in implementation of the study. References 1. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163(7):1723-1729.2. Stoll BJ, Hansen NI, Bell EF, et al. 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Tables Preterm with BPD n =20 Preterm without BPD n =20 At term n =20 BPD vs PRE BPD vs AT PRE vs AT Demographics Current Female n (%) 11 (55) 11 (55) 11 (55) >.999 >.999 >.999 Age years 22 ± 2 23 ± 2 22 ± 2 .404 >.999 .378 Height cm 171 ± 8 178 ± 8 177 ± 9 .702 .052 .649 Weight kg 67 ± 9 72 ± 15 70 ± 11 .248 .545 .843 Body mass index kg m -2 23 ± 2 24 ± 5 22 ± 3 .901 >.999 .350 History of smoking N (%) 4 (20) 6 (30) 3 (15) .716 >.999 .451 Former asthma diagnosis and/or inhalator use N (%) 4 (20) 3 (15) 2 (10) >.999 .661 >.999 Currently using inhalers N (%) 2 (10) 0 (0) 0 (0) .487 .487 >.999 Perinatal Gemelli 4 (20) 3 (15) 1 (5) >.999 .342 .605 Pre-eclampsia/HELLP 4 (20) 5 (25) 0 (0) >.999 .106 .047 Celestone admin 10 (50) 12 (60) 1 (5) .751 .003 <.001 Ceasarean section 10 (50) 8 (40) 0 (0) .751 <.001 .003 Gestational age weeks 27.0 (26.1, 27.9) 28.4 (27.4, 28.6) 39.1 (38.2, 40.1) .287 <.001 <.001 Birth weight g 850 ± 100 1005 ± 200 3300 ± 590 .328 <.001 <.001 Surfactant admission 14 (70) 7 (35) 0 (0) .056 <.001 .008 O 2 - dependency Days 58 (47, 72) 13 (7, 20) 0 (0, 0) .001 .999 >.999 Exercise per week METmin∙10 -3 0.5 (0, 1.6) 0.8 (0.05, 1.6) 1.5 (0.6, 2.4) >.999 .094 .250 Mean±standard deviation, median (IQR) or number (percentage) are given. AT - At term born group, PRE - Preterm born group without bronchopulmonary dysplasia, BPD - preterm born group with bronchopulmonary dysplasia, O 2 – oxygen, IPAQ – international physical activity questionnaire BPD Total n =20 Male n=9 Female n=11 PRE n =20 Male n=9 Female n=11 AT n =20 Male n=11 Female n=9 BPD vs PRE BPD vs AT PRE vs AT Peak values CPET VO 2 ml min -1 2299 ± 492 2638 ± 580 2910 ± 702 .223 .005 .461 Male 2654 ± 398 3139 ± 379 3380 ± 382 .034 .999 .048 .312 Male 39 (33; 40) 38 (36; 46) 48 (45; 50) >.999 .005 .061 Female 33 ± 6 34 ± 7 34 ± 6 .991 .964 .990 VO 2 % of pred 91 ± 18 102 ± 14 106 ± 17 .899 .013 .184 Male 81 ± 10 94 ± 10 102 ± 13 .061 .002 .338 Female 102 ± 15 108 ± 14 111 ± 20 .602 .437 .943 Oxygen pulse ml/beat 13 ± 3 14 ± 3 15 ± 3 .350 .019 .357 Male 15 ± 2 17 ± 2 18 ± 2 .148 .021 .709 Female 11 ± 2 12 ± 2 13 ± 3 .511 .179 .727 Oxygen pulse % of pred 100 ± 18 108 ± 14 111 ± 17 .237 .088 .517 Male 89 ± 12 100 ± 12 105 ± 12 .185 .016 .559 Female 107 ± 19 113 ± 13 118 ± 19 .666 .364 .842 Workload Watt 211 ± 48 238 ± 54 269 ± 67 .168 .006 .168 Male 249 ± 29 285 ± 31 313 ± 39 .074 <.001 .195 Female 179 ± 36 198 ± 29 215 ± 54 .515 .134 .624 Ventilation L min -1 85 ± 19 101 ± 24 112 ± 29 .086 .003 .165 Male 101 ± 15 119 ± 20 126 ± 22 .147 .025 .725 Female 72 ± 11 87 ± 16 95 ± 28 .208 .033 .576 % of pred 69 ± 12 69 ± 13 68 ± 13 .997 .972 .952 Male 71 ± 13 70 ± 14 69 ± 11 .978 .959 .998 Female 67 ± 12 69 ± 12 67 ± 15 .958 .978 .908 Tidal volume ml 2145 ± 589 2454 ± 539 2521 ± 587 .210 .114 .945 Male 2626 ± 402 2838 ± 524 2814 ± 482 .615 .654 .588 Female 1751 ± 387 2141 ± 302 2143 ± 500 .072 .089 .999 Mean±standard deviation, median (IQR) or number (percentage) are given. AT - At term born group, PRE - Preterm born group without bronchopulmonary dysplasia, BPD - preterm born group with bronchopulmonary dysplasia, VO 2 – oxygen consumption, Ti/Ttot – ratio of inspiration time and total tidal time. BPD n =20 PRE n =20 AT n =20 BPD vs PRE BPD vs AT PRE vs AT Baseline (BL) FEV1 L 3.2 ± 0.7 3.9 ± 0.6 4.1 ± 0.9 <.001 <.001 .134 % 79 ± 9 95 ± 8 94 ± 12 <.001 <.001 .955 Z-score -1.73 ± 0.79 -0.41 ± 0.70 -0.49 ± 1.00 <.001 <.001 .957 FVC L 4.4 ± 0.9 4.9 ± 0.9 5.0 ± 1.2 .406 .172 .857 % 96 ± 12 100 ± 8 97 ± 14 .599 .949 .787 Z-score -0.33 ± 1.03 -0.03 ± 0.69 -0.24 ± 1.21 .613 .959 .781 FEV1/VC L 70 ± 9 81 ± 5 82 ± 6 <.001 <.001 .911 % 82 ± 11 94 ± 6 95 ± 7 <.001 <.001 .915 Z-score -2.00 ± 1.12 -0.70 ± 0.76 -0.56 ± 0.86 <.001 <.001 .877 MMEF75/25 L/s 2.0 (1.7; 2.0) 3.6 (3.3; 4.3) 3.8 (3.3; 4.7) <.001 <.001 .637 % 54 ± 17 83 ± 17 84 ± 16 <.001 <.001 .992 Z-score -2.39 ± 0.98 -0.77 ± 0.80 -0.75 ± 0.75 <.001 .999 .094 .266 Z-score -0.56 ± 1.06 -0.46 ± 0.70 0.02 ± 0.78 .922 .091 .193 Post-ventolin FEV1 L 3.5 (2.9; 4.2) 3.9 (3.6; 4.7) 4.3 (3.7; 5.1) .022 .002 .415 Z-score -0.21 ± 1.02 -0.01 ± 0.65 -0.19 ± 1.24 .523 .952 .563 % change vs BL 8.5 (4.7; 12.3) 3.8 (1.4; 6.6) 3.4 (1.8; 4.4) .004 .999 >10% FEV1 change N (%) 7 (35) 2 (10) 0 (0) .127 .008 .487 FVC L 4.7 (3.9; 5.8) 4.5 (4.1; 5.8) 4.6 (3.8; 5.4) >.999 >.999 >.999 Z-score -0.14 ± 0.98 0.08 ± 0.66 -0.10 ± 1.27 .761 .990 .837 % change vs BL 1.0 ± 2.9 0.1 ± 2.0 -0.6 ± 1.8 .415 .089 .658 FEV1/VC L 78.5 ± 7.0 85.3 ± 4.4 86.4 ± 6.0 .002 <.001 .823 Z-score -1.14 ± 1.07 -0.16 ± 0.62 0.04 ± 0.96 .004 .999 MMEF75/25 L/s 72 ± 20 99 ± 17 98 ± 18 <.001 <.001 .997 Z-score -1.34 ± 1.02 -0.07 ± 0.79 -0.14 ± 0.79 <.001 .999 Mean±standard deviation, median (IQR) or number (percentage) are given. BPD - preterm born group with bronchopulmonary dysplasia (NICHD 2001 criteria), PRE - Preterm born group without bronchopulmonary dysplasia, AT - At term born group, O 2 – oxygen, FEV1 – forced expiratory volume in 1 second, (F)VC – (forced) vital capacity, MMEF – maximal mid-expiratory flow, DLCO – diffusion capacity for carbon monoxide. Z-score .999 .231 >.999 Dyspnea d’effort n (%) 3 (15) 3 (15) 2 (10) >.999 >.999 >.999 Coughing n (%) 2 (10) 1 (5) 0 (0) >.999 .487 >.999 Allergies/Rhinitis n (%) 1 (5) 2 (10) 6 (30) >.999 .091 .235 Angina pectoris n (%) 0 (0) 0 (0) 0 (0) >.999 >.999 >.999 Palpitations n (%) 2 (10) 1 (5) 2 (10) >.999 >.999 >.999 Dizziness/syncope n (%) 2 (10) 2 (10) 1 (5) >.999 >.999 >.999 Short form 36 items n=19 n=20 n=20 Physical functioning 95 (83; 100) 100 (96; 100) 100 (95; 100) .020 .068 >.999 Physical limitations 100 (75; 100) 100 (100; 100) 100 (100; 100) .355 .151 >.999 Emotional limitations 100 (100; 100) 100 (100; 100) 100 (67; 100) >.999 >.999 .250 Energy/fatigue 63 ± 19 67 ± 3 68 ± 14 .663 .558 .982 Emotional well-being 82 ± 15 78 ± 13 76 ± 15 .632 .498 >.667 Social functioning 88 ± 17 91 ± 12 89 ± 14 >.999 >.999 >.999 Pain 95 (80; 100) 100 (90; 100) 90 (78; 100) >.999 >.999 .453 General health 80 (50; 95) 83 (70; 94) 80 (70; 90) >.999 >.999 >.999 Mean±standard deviation, median (IQR) or number (percentage) are given. BPD - preterm born group with bronchopulmonary dysplasia (NICHD 2001 criteria), PRE - Preterm born group without bronchopulmonary dysplasia, AT - At term born group, O 2 – oxygen, FEV1 – forced expiratory volume in 1 second, FVC – forced vital capacity, IPAQ – international physical activity questionnaire, LV – left ventricle, RV - right ventricle. Figure legends Figure 1: Forced expiratory volume in 1 second (FEV1) (A), reversibility of FEV1 using salbutamol (B), Tiffeneau index (C) and airway resistance (R aw ) (D) of preterm born young adults with (BPD) and without (PRE) bronchopulmonary dysplasia, and at term born young adults (AT). VC – vital capacity, RV – residual volume. Figure 2: Exploratory data of associations between perinatal factors and physiological parameters in young adults born preterm with (triangles) or without BPD (squares). FEV1 – forced expiratory volume in 1 second, VC – vital capacity. Image (Figure 1.png) is missing or otherwise invalid. Information & Authors Information Version history V1 Version 1 22 April 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords bpd long-term obstructive disease prematurity young adult Authors Affiliations Jarno Steenhorst J Erasmus MC Afdeling Cardiologie View all articles by this author Alain Dubois Erasmus MC View all articles by this author Lidewij Visser S Erasmus MC View all articles by this author Arnold Duinisveld J Erasmus MC View all articles by this author Alexander Hirsch Erasmus MC Afdeling Cardiologie View all articles by this author Irwin Reiss Erasmus MC View all articles by this author Willem Helbing H Erasmus MC View all articles by this author Daphne Merkus Erasmus MC Afdeling Cardiologie View all articles by this author Lieke Kamphuis S [email protected] Erasmus MC View all articles by this author Metrics & Citations Metrics Article Usage 190 views 73 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Jarno Steenhorst J, Alain Dubois, Lidewij Visser S, et al. 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