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Pulmonary function testing in pediatric allogeneic stem cell transplant recipients to monitor for Bronchiolitis obliterans syndrome: a systematic review

BMC Pediatrics volume 25, Article number: 250 (2025) Cite this article

Abstract

Background

Bronchiolitis obliterans syndrome (BOS) represents a significant source of morbidity and non-relapse mortality among children and young adults treated with allogeneic hematopoietic stem cell transplantation (aHSCT). Pulmonary function testing (PFT) pre- and post-aHSCT may allow for pre-symptomatic detection of BOS, and thus early intervention. Current guidelines and practices vary regarding which tests to perform and timing relative to transplant. A systematic review evaluating PFT before and after pediatric aHSCT was conducted to inform American Thoracic Society clinical practice guidelines on detection of BOS.

Objective

To determine the optimal approach to conducting PFT prior to and after pediatric aHSCT.

Study Design

We performed a systematic review of the literature to identify studies of PFT in human aHSCT recipients < 25 years of age to address two questions: (1) Should pre-transplant screening PFT be performed in pediatric patients who will undergo aHSCT? (2) At what frequency should pediatric patients who have had aHSCT undergo PFT? We searched in Medline through August 2022 for studies that enrolled patients < 25 years of age being treated with aHSCT for whom PFT data were reported before or after transplant.

Results

The 30 studies with pre-transplant PFT data showed a wide range of findings, with the majority demonstrating abnormalities. In studies reporting respiratory symptoms, 85–100% of patients were asymptomatic. In the 21 studies reporting post-transplant PFT, 11 used a surveillance strategy where at least one test was performed in the first year post-transplant. Median time to BOS diagnosis was 6–12 months in the regular surveillance studies, and 6–24 months in the others. Forced expiratory volume in one second at the time of BOS diagnosis was 38–84% predicted in studies with regular surveillance versus 44–57% predicted in studies with no surveillance. In the surveillance group, BOS was identified in some patients who were asymptomatic. Data quality in studies reviewed was moderate to very low.

Conclusions

Abnormalities in PFT are common in children prior to aHSCT. Regular monitoring in the first 1–2 years post-aHSCT may improve early and/or pre-symptomatic identification of BOS, but significant limitations may still be seen at the time of diagnosis. Higher quality data are needed.

Peer Review reports

Background

Allogeneic hematopoietic stem cell transplantation (aHSCT) is an important modality for treating hematologic malignancies as well as many non-malignant conditions in children and young adults. Pulmonary complications are relatively common after pediatric aHSCT and cause significant morbidity and mortality [1,2,3,4,5]. Bronchiolitis obliterans, in which immune-mediated injury to the small- and medium-sized airways results in worsening irreversible obstruction with air trapping, is the primary pulmonary manifestation of chronic graft versus host disease (cGVHD) after aHSCT [6]. As lung biopsy may be associated with morbidity in this population [7,8,9], bronchiolitis obliterans syndrome (BOS), based on clinical criteria, is used as proxy. Current diagnostic criteria for BOS are based primarily on post-transplant changes in lung function as measured by spirometry, with supporting features from chest imaging and static lung volumes [10]. As with the form of BOS seen in lung transplant recipients with allograft rejection [11], BOS due to cGVHD can be associated with rapid clinical decline [6].

Under current National Institutes of Health consensus criteria [10], pulmonary function testing (PFT) is required to diagnose BOS. This is established by (1) forced expiratory volume in one second (FEV1) < 75% predicted and an irreversible decline ≥ 10% in under two years, (2) ratio of FEV1 to vital capacity < 0.7 or below the lower limit of the 90% confidence interval, (3) absence of infection, and (4) either: (a) cGVHD in at least one organ system, or air trapping evidenced by (b) expiratory chest computed tomography, or (c) residual volume (RV) > 120% predicted or RV/total lung capacity (TLC) > 90% confidence interval.

Monitoring aHSCT recipients with serial PFT allows for objective longitudinal assessment, with the goal of identifying pre-symptomatic BOS. A greater impairment in lung function at the time of diagnosis has been associated with worse outcomes in cohort studies including mostly adult transplant recipients [12, 13]. Although currently available therapies for BOS are somewhat limited [14], evidence from adult studies suggests that early intervention could potentially arrest or slow decline in lung function with improved outcomes [13, 15, 16]. While all current pediatric guidelines recommend PFT surveillance in aHSCT recipients, the recommended frequency ranges from every three months to annually in the first year post-transplant, with variability in which specific tests are recommended [17,18,19,20]. Additionally, practice patterns vary across pediatric transplant centers [21].

In 2022-23, an American Thoracic Society (ATS) working group prepared clinical practice guidelines on the detection of bronchiolitis obliterans in pediatric aHSCT patients [22]. Two of the questions addressed by these guidelines relate to the timing of PFT and specific tests to be performed prior to and after aHSCT. The following systematic review was completed to inform the guideline committee’s recommendations regarding these questions.

Methods

We synthesized the best available evidence for the following two Population, Intervention, Comparator, and Outcome (PICO) questions:

1. Patients: Children and young adults (< 25 years of age) scheduled to undergo aHSCT.

Intervention: Pre-transplant PFT using spirometry, measurement of static lung volumes, or diffusion capacity for carbon monoxide (DLCO).

Comparator: No PFT.

Outcomes: Diagnostic yield (abnormal PFT), BOS diagnosis post-transplant, BOS severity at diagnosis, post-transplant mortality.

2. Patients: Children and young adults (< 25 years of age) who underwent aHSCT.

Intervention: Post-transplant surveillance PFT (at least two tests in the first 12 months after aHSCT) using spirometry, measurement of static lung volumes, or DLCO.

Comparator: No surveillance PFT.

Outcomes: Diagnostic yield (abnormal PFT), timing of BOS diagnosis, BOS severity at diagnosis, mortality, supplemental oxygen use.

Electronic literature searches were conducted by a medical librarian. Standard methodology for conducting systematic reviews as per guidelines provided by the Cochrane Handbook for Systematic Reviews of Interventions were followed [23]. Search results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [24].

Study identification and eligibility

Study identification and eligibility criteria were developed and documented in a search strategy (Table 1) using the PICO framework as described in the Cochrane Handbook [23]. We performed literature searches in July-August 2022 in Medline (via OvidSP) to identify studies describing pulmonary function testing in children and young adults undergoing aHSCT transplantation. In addition to bibliographic databases, a manual search was performed on the reference lists of identified eligible studies, and the guideline panelists were asked to identify additional studies that may be relevant which were not identified in the search.

Table 1 Search strategy utilized to identify the 2003 abstracts selected for full-text review
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Study screening and ascertainment of eligibility

Eligibility criteria were developed by the project team and checked by the lead methodologist. Before the screening began, duplicate studies and those that did not meet language or date restrictions were excluded. The screening procedure was conducted in a two-step process: (1) title/abstract screening and (2) full-text screening. Title/abstract screening was conducted by two screeners using Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia) and checked by the lead methodologist. Full-text screening was conducted by two independent reviewers. Discrepancies between reviewers were identified and resolved by an independent third reviewer.

We included observational studies that reported results of PFT before or after the transplantation of any follow-up duration. We only included studies reported as full text articles. Conference abstracts were not included in this review. We included studies of patients < 25 years of age who were either scheduled for or received aHSCT. Studies of adult and pediatric patients where data from children and young adults were separately reported were also included. We did not exclude any primary conditions leading to aHSCT.

Data extraction

Data from relevant studies were extracted using a specifically developed standardized data extraction form. For each trial, study, patient, and treatment characteristics, as well as PFT results, and data about BOS were extracted. For cohort studies, the proportion of patients diagnosed with PFT abnormalities prior to transplant were noted. We recorded the changes in post-transplant PFT results over time, proportion of patients diagnosed with BOS, and the symptomatology of patients at the time of BOS diagnosis.

Risk of bias assessment

Risk of bias (study quality) of included studies was assessed using the Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomized studies [25]. In brief, this tool includes three domains: patient selection, comparability, and outcomes. The risk of bias for each study and the overall risk of bias for individual outcomes is reported in three categories which correspond to no serious risk, serious risk and very serious risk of bias.

Evidence tables

Evidence tables were created to summarize estimated effects on an outcome-by-outcome basis. The evidence tables were used by the guideline committee to inform clinical recommendations.

Protocol Registration

The protocol for the systematic review has been registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols [26] (registration number: INPLASY202450075, DOI:https://doiorg.publicaciones.saludcastillayleon.es/10.37766/inplasy2024.5.0075). Details of the protocol for the systematic review can be accessed at https://inplasy.com/inplasy-2024-5-0075/.

Results

For the two PICO questions, we screened 2003 abstracts. Of these, two were duplicates, and from the 2001 unique abstracts, we selected 121 for full review. We ultimately utilized 30 studies [27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56] to address PICO 1, and 21 studies [27,28,29, 31, 34, 37, 38, 42, 46, 48, 50, 54,55,56,57,58,59,60,61,62,63] to address PICO 2. The PRISMA flow diagrams are illustrated in Fig. 1 (PICO 1) and Fig. 2 (PICO 2). All studies included are summarized in Table 2 (PICO 1) and Table 3 (PICO 2).

Fig. 1
figure 1

PRISMA diagram illustrating selection of studies for PICO 1

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Fig. 2
figure 2

PRISMA diagram illustrating selection of studies for PICO 2

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Table 2 Summary of the 30 studies included for PICO 1
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Table 3 Summary of the 21 studies included for PICO 2
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Pre-transplant testing

We gathered data on PFT results pre-aHSCT and association with development of BOS as well as the following additional clinical outcomes: post-aHSCT pulmonary complications, intensive care unit (ICU) admissions, and mortality. The studies selected included patients who underwent any type of aHSCT -- most received bone marrow transplantation -- and had pre-transplant PFT results reported. Not all studies used the same normative data for determining percent of predicted values, and abnormalities were defined differently across studies. Similarly, those that defined restrictive and obstructive patterns used slightly different definitions. Of the six studies that reported pre-transplant static lung volumes, one utilized gas washout [32], and the others, body plethysmography [30, 37, 43, 47, 53]. When available, we included data on the development of BOS. The age range for patients included in the selected studies was 0.3–23 years of age. The year of transplant was before 2000 for all patients in 12 studies, after 2000 for all patients in 16 studies, while two included patients transplanted both before and after 2000. Of the 37 studies used for either PICO 1 or 2 (Tables 2 and 3), 14 reported data both before and after aHSCT [27,28,29, 31, 34, 37, 38, 42, 46, 48, 50, 54,55,56].

The findings for pre-aHSCT spirometry parameters and DLCO are summarized in Table 4. Because of the wide prevalence ranges of abnormalities and retrospective cohort nature of all studies, most were determined to be of moderate quality. Most studies for PICO 1 were determined to have low risk of bias. For those that had higher risk, this was due to a lack of diversity in diagnosis requiring aHSCT, thus limiting the generalizability of the findings from these studies (Fig. 3 and Supplemental Table 1).

Fig. 3
figure 3

Risk of bias assessment for the 30 studies used to address PICO 1

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Table 4 Evidence profile of pre-transplant PFT data (PICO 1)
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Table 5 Evidence profile of post-transplant outcomes for patients undergoing post-transplant surveillance PFT versus patients who did not receive post-transplant surveillance PFT (PICO 2)
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Spirometry

All studies included reported some spirometry data. The definition of abnormal results varied between studies, but most used a threshold of < 80% of predicted value, although different reference equations were utilized. As shown in Table 4, the most commonly reported pre-aHSCT parameter was FEV1 in 16 studies [29,30,31,32, 35,36,37, 40, 42, 45,46,47, 50, 52, 54, 56]. Ten reported forced vital capacity (FVC) [32, 35,36,37, 40, 41, 47, 50, 54, 56], thirteen reported ratio of FEV1/FVC [27, 29, 30, 32, 35,36,37, 40, 41, 50, 52, 55, 56], and four reported forced expiratory flow between 25 and 75% of vital capacity (FEF25-75%) [32, 36, 47, 56].

Total lung capacity

As shown in Table 4, pre-transplant TLC was reported in six studies. The mean TLC was within normal limits in one [30], and among the remaining five studies [32, 37, 41, 43, 47], the prevalence of abnormalities ranged from 9 to 29%.

Diffusion capacity

Results from the ten studies reporting DLCO [30, 32, 37, 41, 43, 45, 47, 50, 52, 55] are summarized in Table 4.

Restriction and obstruction

Nine studies [32, 33, 40, 43,44,45, 47, 48, 55] reported patterns of abnormalities, either from spirometry, static lung volumes, or both. The prevalence of a restrictive pattern ranged from 7 to 50%, obstructive pattern 0–24%, and mixed pattern 1–2%.

Respiratory symptoms

Five studies [37, 52, 53, 55, 64] provided data on presence of respiratory symptoms, with 85–100% reporting no symptoms prior to transplant.

Association with BOS

Association between pre-aHSCT spirometry was analyzed in seven studies [29, 34, 38, 42, 54, 56, 64] but none reported any statistically significant association between any pre-aHSCT spirometry parameter and development of BOS.

Mortality and other clinical outcomes

Kaya et al. [37] found that lower pre-transplant FEV1 and/or FVC were associated with increased odds of respiratory failure leading to mechanical ventilation, with high rates of mortality among ventilated patients. Lee et al. [39] reported an association between lower pre-aHSCT hemoglobin-adjusted DLCO and higher mortality. Quigg et al. [45] found abnormal pre-aHSCT DLCO adjusted for hemoglobin and alveolar volume was predictive of mortality in univariate analysis. Srinivasan et al. [47] reported decreased FEV1, FVC, TLC, RV, and the presence of restrictive lung disease were all associated with poor survival in multivariate analysis.

Five studies examined pre-aHSCT PFT results in relation to pulmonary outcomes other than BOS, ICU admissions, and mortality, with mixed findings. One found that pre-aHSCT PFT results were not predictive of post-transplant severe obstructive lung disease or worsening changes on chest computed tomography scan [38]. Another compared patients who developed any late-onset non-infectious pulmonary complications versus those who did not, and found that pre-aHSCT PFT parameters were similar in both groups [42]. In 2014, Srinivasan et al. [47] reported that lower pre-transplant FEF25–75% was associated with increased risk of subsequent pulmonary complications. Finally, a later study by Srinivasan et al. [48] found that T-cell depletion, reduced pre-transplantation FEV1, and cGVHD were associated with increased risk for pulmonary complications.

Frequency of post-transplant testing

The studies reviewed for this PICO question are listed in Table 3. We gathered data on whether PFT was performed post-transplant, and if so, the frequency of testing. We categorized studies into those that included at least one scheduled PFT measurement within the first 12 months post-transplant (regular surveillance) and those where PFT was not performed during this time frame, or only in patients with symptoms. As with PICO question 1, we collected data on development of BOS or obstructive lung disease, and additional clinical outcomes including pulmonary complications, ICU admission, and mortality.

The aggregate findings for studies with regular surveillance versus those without are summarized in Table 5. Several studies for PICO 2 were determined to have serious risk of bias, and the data thus were deemed low to very low quality. A wide range of BOS severity was reported among studies, and some studies included only patients with BOS. Some studies only described obstructive airway disease without specifically addressing whether formal criteria for BOS were met. For this review, we treated obstructive lung disease as synonymous with BOS, understanding that this may result in some misclassification. Additionally, confounding variables such as conditioning regimens and pre-existing abnormal lung function tests were not controlled in most studies (Fig. 4 and Supplemental Table 2).

Fig. 4
figure 4

Risk of bias assessment for the 21 studies used to address PICO 2

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Post-transplant surveillance

The year of transplant was before 2000 for all patients in nine studies, after 2000 for all patients in ten studies, while two studies included patients transplanted before and after 2000. Of the 21 studies, 11 reported regular post-aHSCT surveillance of PFT, and ten reported no regular surveillance. In nine of these 11, surveillance was performed with spirometry, measurement of static lung volumes, and DLCO. The other two studies used only spirometry. All studies reported FEV1 at a minimum. Of the nine studies reporting static lung volumes, five used body plethysmography [27, 37, 38, 48, 57], two used gas dilution [50, 55], and the authors did not state which technique was used in the remaining two [31, 56]. Among the 11 with regular surveillance, the frequency of testing ranged from one test in the first six months post-transplant in the oldest study [57] to every three months [27, 37]. All studies included pre-transplant PFT results for each patient, which were used as baseline values. Three studies reported regular PFT through 24 months post-aHSCT, and two performed PFT annually after the first 12 months. The most common schedule for PFT was pre-transplant, then 3, 6, 9–12, and 24 months post-transplant. Among patients both with and without BOS, a decline in lung function was observed between 3 and 9 months post-transplant; while some showed improvement between 6 and 24 months, others had continued decline for up to 10 years, sometimes without symptoms [28, 58, 60].

Identification of BOS

Median time to identification of BOS in the 11 studies with regular surveillance was 6–12 months, with a range of 1–60 months. Mean percent predicted FEV1 was 38–84% at the time of diagnosis [34, 38]. Two studies reported a total of four patients who had not yet developed respiratory symptoms at the time of BOS diagnosis [31, 34]. Abnormalities in PFT results were associated with presence of cGVHD in other organ systems. One study that utilized spirometry, DLCO, and static lung volumes reported that DLCO and TLC were most associated with respiratory failure in the setting of BOS [37]. Jung et al. [34] reported that the extent of drop in FEV1 from pre-aHSCT to the time of diagnosis of BOS was not associated with mortality; however, the values of FEV1 were significantly lower at 6, 9, and 18 months after BOS diagnosis for patients who eventually died or received lung transplantation. Ten studies did not utilize regular post-transplant PFT. In these, participants were tested at the time of symptom onset or some point thereafter. The median time to diagnosis of BOS was 6–24 months in these studies, with diagnosis occurring as far out as 107 months post-transplant. Mean percent predicted FEV1 at diagnosis was 44–57% [46, 63], with one study reporting a mean FEV1 z-score of -3.62 [61]. In a small cohort study of 20 children with obstructive lung disease after aHSCT, reduced mid-expiratory flow rate and elevated RV at the time of diagnosis of obstruction were associated with decreased response to immunosuppressive therapy [46].

Discussion

This systematic review was conducted to inform ATS guidelines on detection of BOS among pediatric aHSCT recipients. We have identified data suggesting that performing PFT pre-transplant, and at regular intervals in the first 1–2 years after transplant, may improve early identification of BOS. However, the data suggest some limitations of this approach, as BOS was often diagnosed at a point where significant pulmonary function impairment had already occurred.

The reviewed literature suggests that assessment of pre-aHSCT pulmonary function is useful for several reasons. The first is that abnormal pulmonary function is not uncommon prior to transplant. This is not surprising given that pediatric patients undergoing aHSCT are often at risk of pulmonary disease from a number of possible causes: sequelae of the primary disease process, airway or parenchymal injury from respiratory infections, as well as damage from prior chemo- or radiation therapy [1]. Identification of pulmonary function impairment pre-aHSCT allows for thorough evaluation and treatment of any identified pathology prior to transplant. Further, accurate determination of pre-aHSCT pulmonary function is vital for interpreting post-transplant results. If pulmonary function impairment is not identified pre-aHSCT, its discovery post-transplant will trigger concern for a transplant-related complication, resulting in a cascade of unnecessary investigation and treatment which could lead to patient harm. Lastly, there are data to suggest that pre-aHSCT pulmonary function is associated with post-transplant outcomes, pulmonary complications, need for mechanical ventilation, and mortality. If these findings are confirmed in future studies, then pre-aHSCT pulmonary function may allow for more personalized monitoring strategies for pulmonary complications, and more informed counseling of patients and families regarding the risks of aHSCT.

Post-transplant surveillance PFT also has value as it can lead to identification of BOS before overt symptoms develop, with a shorter median time to diagnosis than using symptom-triggered testing. Even with earlier detection of BOS, the level of pulmonary function impairment at the time of BOS diagnosis is significant. This is true even in studies which used the most frequent surveillance schedule of testing every three months, suggesting that BOS-related pulmonary function impairment occurs rapidly. While even more frequent testing may allow for detection of very early disease, studies are needed to assess the feasibility and efficacy of such an approach.

Because evidence suggests existing therapies may be more effective if given early in disease evolution [13, 15, 16], patients ideally would be diagnosed before significant impairment has occurred. Further evaluation [65] may be necessary when PFT abnormalities are detected, as it is possible that pulmonary function limitations in patients with cGVHD could reflect involvement of the chest wall fascia or respiratory muscles, or acute respiratory infection, rather than the airway injury typical of bronchiolitis obliterans [6]. Interventions or infections over the course of the transplant may also affect post-transplant PFT results. Some studies have reported cases of histology-proven bronchiolitis obliterans which do not meet criteria for BOS [29, 66], indicating that biopsy may still be considered in cases where suspicion is high regardless of PFT results. Development of pediatric-specific diagnostic criteria for BOS may offer the opportunity for improved detection in this population [2, 67].

When assessing the implementation of post-aHSCT surveillance testing, in addition to diagnostic yield, it is important to consider additional factors such as access (both to the test, and care that is needed for any abnormal results), cost, and experience of patients and families. In general, aHSCT is performed in highly-resourced settings, with previous work showing ample access to PFT as well as any subsequent tests and medical care that are needed following an abnormal result [21]. The costs of surveillance PFT are negligible compared to the aggregate costs of transplantation. Patients who receive aHSCT experience surveillance testing for other post-transplant complications, and PFT are non-invasive and generally acceptable.

The studies reviewed here have some limitations, many of which are related to cohort effects. Most studies included are single-center, and thus results may reflect practices specific to the study sites, which introduces heterogeneity and may limit generalizability. Inclusion criteria differ across studies, resulting in variability in several domains, including patient age, primary diagnosis, and type of transplant. We utilized a broad age range in our search strategy to be fully inclusive of the entire population that may be treated at pediatric transplant centers. Our inclusion of young adults may not reflect the population treated at all pediatric centers, limiting generalizability. The broad age range makes detection of associations more difficult, as susceptibility of patients to BOS and/or ability of PFT to detect changes may vary by age. Because transplantation is a dynamic field, practices change over time, and patients in older studies may differ in important ways from those currently undergoing aHSCT. Samples sizes in many of the studies are relatively small, resulting in limited statistical power to detect subtle associations. The use of different reference datasets, and variable definitions of restrictive and obstructive disease, limits the comparability of studies. In studies without regular PFT surveillance, death from undiagnosed BOS may lead to survivorship bias in post-transplant PFT results. Lastly, limited data are available regarding whether surveillance PFT impacts important clinical outcomes such as ICU admission and mortality.

This review also highlights several areas where data are lacking. Prospective studies are needed to more fully characterize the relationships between pre-transplant PFT with later pulmonary complications and mortality. More data are required to determine optimal monitoring schedules and techniques to detect complications and optimize outcomes. Research is also needed on other modalities of testing more suited to younger patients, such as infant PFT, oscillometry, and multiple breath washout [68]. Large multicenter studies and registries would be ideal to address these and other critical questions to improve outcomes in this vulnerable population.

Data availability

All data generated of analyzed during this study are included in this published article/ The authors can be contacted to provide any further detail on data extracted from the included papers.

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Acknowledgements

Nil.

Funding

No funding was received for this review directly, but the clinic guideline development process was sponsored and funded by the American Thoracic Society.

Author information

Authors and Affiliations

  1. Division of Pediatric Pulmonology, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    William A. Gower

  2. Division of Pulmonary and Critical Care, Michigan State University College of Human Medicine and Spectrum Health, Grand Rapids, MI, USA

    Maximiliano Tamae-Kakazu

  3. Respiratory and Sleep Medicine, Royal Children’s Hospital, Melbourne, Australia

    Shivanthan Shanthikumar

  4. Respiratory Diseases, Murdoch Children’s Research Institute, Melbourne, Australia

    Shivanthan Shanthikumar

  5. Department of Paediatrics, University of Melbourne, Melbourne, Australia

    Shivanthan Shanthikumar

  6. Department of Pediatrics, University of Tennessee College of Medicine and Le Bonheur Children’s Hospital, Memphis, TN, USA

    Saumini Srinivasan

  7. St. Jude Children’s Research Hospital, Memphis, TN, USA

    Saumini Srinivasan

  8. Woodruff Health Sciences Center Library, Emory University, Atlanta, GA, USA

    Erin E. Reardon

  9. Laboratory of Asthma and Lung Inflammation, Critical Care Medicine and Pulmonary Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    Amisha V. Barochia

  10. Department of Internal Medicine, Saint Louis University, St Louis, MO, USA

    Edward Charbek

  11. Pediatric Hematology and Immunology Department, Robert Debré Academic Hospital, GHU APHP Nord - Université de Paris, Paris, France

    Charlotte Calvo

  12. Human Immunology, Pathophysiology and Immunotherapy, Institut de Recherche Saint-Louis, Paris, France

    Charlotte Calvo

  13. Division of Pediatric Pulmonology, Allergy, and Sleep Medicine, Riley Hospital for Children, Indianapolis, IN, USA

    Pi Chun Cheng

  14. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA

    Pi Chun Cheng

  15. Department of Pediatrics, Division of Pulmonary Medicine, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX, USA

    Shailendra Das

  16. Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Stella M. Davies

  17. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Stella M. Davies & Christoper T. Towe

  18. Division of Pulmonary and Sleep Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Jessica Gross

  19. Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Ajay Sheshadri

  20. Division of Pulmonary Medicine, Cincinnati Children’s Hospital, Cincinnati, OH, USA

    Christoper T. Towe

  21. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    Samuel B. Goldfarb

  22. Division of Pulmonary Medicine, Masonic Children’s Hospital, Minneapolis, MN, USA

    Samuel B. Goldfarb

  23. Division of Neonatology, Fetal and Neonatal Institute, Keck School of Medicine, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA

    Narayan P. Iyer

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  1. William A. Gower
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Contributions

WAG – wrote manuscript. Reviewed and synthesized data. M TK, AVB, EC – performed abstract screening and extracted data from included paers. Reviewed and edited manuscript. EER – performed literature searchesSSh, SSr, CC, PCC, SD, SMD, JG, AS, CTT. SBG – Reviewed and synthesized data. Reviewed and edited manuscript. NPI – oversight of methodology and project overall. Reviewed and edited manuscript.

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Correspondence to William A. Gower.

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Gower, W.A., Tamae-Kakazu, M., Shanthikumar, S. et al. Pulmonary function testing in pediatric allogeneic stem cell transplant recipients to monitor for Bronchiolitis obliterans syndrome: a systematic review. BMC Pediatr 25, 250 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12887-025-05501-2

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Keywords

BMC Pediatrics

ISSN: 1471-2431

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