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Purpose: The Pediatric Oncology Group of Ontario (POGO) supported an effort to implement infection management care pathways based on clinical practice guidelines, to improve the consistency of infection management in pediatric cancer patients. The objective of this qualitative study was to describe the perspective of healthcare professionals (HCPs) following implementation., Methods: Four tertiary pediatric oncology centers in Ontario, Canada, implemented the pathways. We randomly identified three HCPs per group (clinical pharmacists; nurse case managers, educators or practitioners and physician assistants; pediatric oncology fellows; or pediatric oncology staff physicians) per site and invited them to participate in a qualitative interview. One-on-one interviews were conducted remotely, followed by thematic analysis of interview transcripts., Results: A total of 66 invitations were extended and 42 HCPs participated. Identified themes were: (1) implementation approach, (2) access and navigation, (3) engagement, (4) concerns, (5) workplace benefits, (6) reception, and (7) provincial harmonization. HCPs preferred in-person implementation strategies over e-mail communication. They identified teaching/educational utility and benefits to non-oncology departments and non-tertiary centers participating in shared care of patients. Other positive aspects related to evidence-based practice, safety, supporting oncology HCPs, and benefits to patients and families. Concerns included need to ensure users applied clinical judgement and loss of autonomy. Provincial harmonization of practice was viewed positively, although potential logistical and institutional cultural barriers were raised., Conclusions: Following infection management care pathway implementation, HCPs described educational utility and benefits to non-oncology departments, oncology HCPs, patients, and families. Our findings may facilitate future infection management care pathway provincial harmonization., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter technique, and specific airway resistance. However, there has not been a systematic comparison of BDR thresholds across studies yet., Methods: A systematic review was performed on all studies up to May 2023 measuring a bronchodilator effect in children 2-6 years old using one of these techniques (PROSPERO CRD42021264659). Studies were identified using MEDLINE, Cochrane, EMBASE, CINAHL via EBSCO, Web of Science databases, and reference lists of relevant manuscripts., Results: Of 1224 screened studies, 43 were included. Over 85% were from predominantly European ancestry populations, and only 22 studies (51.2%) calculated a BDR cutoff based on a healthy control group. Five studies included triplicate testing with a placebo to account for the within-subject intrasession repeatability. A relative BDR was most consistently reported by the included studies (95%) but varied widely across all techniques. Various statistical methods were used to define a BDR, with six studies using receiver operating characteristic analyses to measure the discriminative power to distinguish healthy from wheezy and asthmatic children., Conclusion: A BDR in 2- to 6-year-olds cannot be universally defined based on the reviewed literature due to inconsistent methodology and cutoff calculations. Further studies incorporating robust methods using either distribution-based or clinical anchor-based approaches to define BDR are required., (© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Rhinovirus (RV) positive bronchiolitis episodes in infancy confer a higher risk to develop asthma in later childhood with associated lung function impairments. We aimed to investigate the association between the type of virus causing a bronchiolitis hospitalization episode and lung ventilation inhomogeneities at preschool age., Methods: Infants hospitalized with a clinical diagnosis of moderate (ward admission) or severe (pediatric intensive care ward admission) bronchiolitis were prospectively followed-up at preschool age to assess nitrogen (N 2 ) multiple breath washout (MBW). Lung clearance index (LCI), functional residual capacity (FRC), and concentration normalized phase III slope analysis (Sn III ) indices were reported from ≥2 technically acceptable trials. Differences between groups were calculated using logistic and linear regression and adjusted for confounders (sex, age at bronchiolitis admission, height at visit, maternal asthma, and doctor-diagnosed asthma, including interaction terms between the latter three). An interaction term was included in a regression model to test for an interaction between RV bronchiolitis severity and MBW parameters at preschool age., Results: One hundred and thirty-nine subjects attended preschool follow-up, of which 84 out of 103 (82%) performing MBW had technically acceptable data. Children with a history of RV positive bronchiolitis (n = 39) had increased LCI (adjusted β-coefficient [aβ] = 0.33, 95% confidence interval [CI] 0.02-0.65, p = 0.040) and conductive airways ventilation inhomogeneity [S cond ] (aβ = 0.016, CI 0.004-0.028, p = 0.011) when compared with those with a RV negative bronchiolitis history (n = 45). In addition, we found a statistical interaction between RV bronchiolitis and bronchiolitis severity strengthening the association with LCI (aβ = 0.93, CI 0.20-1.58, p = 0.006)., Conclusion: Children with a history of hospital admission for RV positive bronchiolitis in infancy might be at a higher risk of lung ventilation inhomogeneities at preschool age, arising from the peripheral conducting airways., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Purpose: This study describes chemotherapy-induced nausea and vomiting (CINV) control rates in pediatric and adult patients who did or did not receive guideline-consistent CINV prophylaxis., Methods: We conducted a systematic literature review of studies published in 2000 or later that evaluated CINV control in patients receiving guideline-consistent vs. guideline-inconsistent CINV prophylaxis and reported at least one CINV-related patient outcome. Studies were excluded if the guideline evaluated was not publicly available or not developed by a professional organization. Over-prophylaxis was defined as antiemetic use recommended for a higher level of chemotherapy emetogenicity than a patient was receiving., Results: We identified 7060 citations and retrieved 141 publications for full-text evaluation. Of these, 21 publications (14 prospective and seven retrospective studies) evaluating guidelines developed by six organizations were included. The terms used to describe CINV endpoints and definition of guideline-consistent CINV prophylaxis varied among studies. Included studies either did not address over-prophylaxis in their definition of guideline-consistent CINV prophylaxis (48%; 10/21) or defined it as guideline-inconsistent (38%; 8/21) or guideline-consistent (3/21; 14%). Eleven included studies (52%; 11/21) reported a clinically meaningful improvement in at least one CINV endpoint in patients receiving guideline-consistent CINV prophylaxis. Ten reported a statistically significant improvement., Conclusions: This evidence supports the use of guideline-consistent prophylaxis to optimize CINV control. Institutions caring for patients with cancer should systematically adapt CINV CPGs for local implementation and routinely evaluate CINV outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Fetal exposure to tobacco smoking throughout pregnancy is associated with wheezing in infancy. We investigated the influence of in utero smoking exposure on lung ventilation homogeneity and the relationship between lung ventilation inhomogeneity at 7 weeks of age and wheezing in the first year of life., Methods: Maternal smoking was defined as self-reported smoking of tobacco or validated by exhaled (e)CO > 6 ppm. Lung function data from healthy infants (age 5-9 weeks) born to asthmatic mothers and parent-reported respiratory questionnaire data aged 12 months were collected in the Breathing for Life Trial (BLT) birth cohort. Tidal breathing analysis and SF 6 -based Multiple Breath Washout testing were performed in quiet sleep. Descriptive statistics and regression analysis were used to assess associations., Results: Data were collected on 423 participants. Infants born to women who self-reported smoking during pregnancy (n = 42) had higher lung clearance index (LCI) than those born to nonsmoking mothers (7.90 vs. 7.64; p = .030). Adjusted regression analyzes revealed interactions between self-reported smoking and LCI (RR: 1.98, 95% CI: 1.07-3.63, 0.028, for each unit increase in LCI) and between eCO > 6 ppm and LCI (RR: 2.25, 95% CI: 1.13-4.50, 0.022) for the risk of wheeze in the first year of life., Conclusion: In utero tobacco smoke exposure induces lung ventilation inhomogeneities. Furthermore, an interaction between smoke exposure and lung ventilation inhomogeneities increases the risk of having a wheeze in the first year of life., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: This study aimed to determine the proportion of patients receiving clinical practice guideline (CPG)-inconsistent care related to chemotherapy-induced vomiting (CIV) prophylaxis, and to describe the association between CPG-inconsistent care and site size. The association between delivery of CPG-inconsistent care and patient outcomes (CIV control, admission prolongation, and unplanned healthcare visits) was also described., Methods: This was a retrospective study conducted at Children's Oncology Group (COG) National Cancer Institute Community Oncology Research Program (NCORP) sites. Eligible patients received highly (HEC) or moderately emetogenic chemotherapy (MEC) as inpatients from January 2014 through December 2015, and were previously enrolled in a COG study. The COG generated a patient list from which patients were randomly selected for chart review by participating sites. A central panel adjudicated CIV prophylaxis received as CPG-consistent or -inconsistent., Results: Twenty-four sites participated. Over half of patients received CPG-inconsistent CIV prophylaxis (HEC: 59/112, 52.6%; MEC: 119/215, 55.3%). The most common reasons for CPG-inconsistency were shortened duration of antiemetic administration or omission of dexamethasone. Site size was not found to be associated with CPG-inconsistent care delivery (HEC: adjusted odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.76-1.23; MEC: adjusted OR: 1.07; 95% CI: 0.92-1.24). Additionally, there was no statistically significant association between receipt of CPG-inconsistent care and patient outcomes., Conclusions: Patients receiving MEC or HEC often received CPG-inconsistent CIV prophylaxis. Site size was not associated with receipt of CPG-inconsistent care. Future studies should evaluate strategies to improve CIV control among pediatric oncology patients including those aimed at improving CPG adherence., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Small airway dysfunction (SAD) is increasingly recognized as an important feature of pediatric asthma yet typically relies on spirometry-derived FEF 25-75 to detect its presence. Multiple breath washout (MBW) and oscillometry potentially offer improved sensitivity for SAD detection, but their utility in comparison to FEF 25-75 , and correlations with clinical outcomes remains unclear for school-age asthma. We investigated SAD occurrence using these techniques, between-test correlation and links to clinical outcomes in 57 asthmatic children aged 8-18 years., Methods: MBW and spirometry abnormality were defined as z -scores above/below ± 1.96, generating MBW reference equations from contemporaneous controls ( n  = 69). Abnormal oscillometry was defined as > 97.5 th percentile, also from contemporaneous controls ( n  = 146). Individuals with abnormal FEF 25-75 , MBW, or oscillometry were considered to have SAD., Results: Using these limits of normal, SAD was present on oscillometry in 63% (resistance at 5-20 Hz; R5-R20; >97.5 th percentile), on MBW in 54% (S cond ; z -scores> +1.96) and in spirometry FEF 25-75 in 44% of participants ( z -scores< -1.96). SAD, defined by oscillometry and/or MBW abnormality, occurred in 77%. Among those with abnormal R5-R20, S cond was abnormal in 71%. Correlations indicated both R5-R20 and S cond were linked to asthma medication burden, baseline FEV 1 and reversibility. Additionally, S cond correlated with F E NO and magnitude of bronchial hyper-responsiveness. SAD, detected by oscillometry and/or MBW, occurred in almost 80% of school-aged asthmatic children, surpassing FEF 25-75 detection rates., Conclusions: Discordant oscillometry and MBW abnormality suggests they reflect different aspects of SAD, serving as complementary tools. Key asthma clinical features, like reversibility, had stronger correlation with MBW-derived S cond than oscillometry-derived R5-R20.

Background: The primary objective was to measure adherence to clinical practice guideline (CPG) recommendations for fertility preservation (FP) in pediatric cancer patients treated in National Cancer Institute Community Oncology Research Program (NCORP) sites. Secondary objectives were to describe factors such as site size associated with CPG-inconsistent care delivery and cryopreservation completion. Methods: This retrospective, multicenter study included patients 15 to 21 years old with a first cancer diagnosis from January 2014 through December 2015 who were previously enrolled to a Children's Oncology Group (COG) study and received care at a participating NCORP site. Patients were randomly selected from a list generated by the COG for chart review by participating sites. Primary outcome was care delivery that was inconsistent with a strong CPG recommendation on FP, namely discussion and offering of FP options before cancer treatment initiation, as adjudicated centrally by a panel. Results: A total of 129 patients from 25 sites were included. Among these, 48% (62/129) received CPG-inconsistent care. Most CPG-inconsistent care was due to lack of FP discussion documentation (93.5%, 58/62). Small site size, treatment at a pediatric (vs mixed adult/pediatric) site, and female sex were associated with higher odds of CPG-inconsistent care delivery. Conclusions: Newly diagnosed pediatric cancer patients often received CPG-inconsistent care for FP, with disproportionate gaps noted for females, and those treated at smaller or pediatric NCORP sites. The primary reason for CPG-inconsistent care is lack of FP discussion from clinicians. Opportunities to improve FP CPG implementation are highlighted.

Background: Multiple breath washout is a lung function test based on tidal breathing that assesses lung volume and ventilation distribution. The aim of this analysis was to use the Global Lung Function Initiative methodology to develop all-age reference equations for the multiple breath washout indices lung clearance index (LCI) and functional residual capacity (FRC)., Methods: Multiple breath washout data from healthy individuals were collated from sites. Data were re-analysed using the latest software versions. Reference equations were derived using the lambda-mu-sigma (LMS) method using the generalised additive models of location shape and scale programme in R. The impact of equipment type, inert tracer gas, and equipment dead space volume on the derived reference ranges were investigated., Results: Data from 23 sites (n=3647 test occasions) were submitted. Reference equations were derived from 1581 unique observations from participants between the ages of 2 and 81 years. Equipment type, inert tracer gas, and equipment dead space volume did not significantly affect the prediction equations for either LCI or FRC. Reference equations for LCI include age as the only predictor, whereas sex-specific reference equations for FRC included height and age., Conclusions: Global Lung Function Initiative reference equations for multiple breath washout variables provide a standard for reporting and interpretation of LCI and FRC., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Effective detection of early lung disease in cystic fibrosis (CF) is critical to understanding early pathogenesis and evaluating early intervention strategies. We aimed to compare ability of several proposed sensitive functional tools to detect early CF lung disease as defined by CT structural disease in school aged children., Methods: 50 CF subjects (mean±SD 11.2 ± 3.5y, range 5-18y) with early lung disease (FEV 1 ≥70 % predicted: 95.7 ± 11.8 %) performed spirometry, Multiple breath washout (MBW, including trapped gas assessment), oscillometry, cardiopulmonary exercise testing (CPET) and simultaneous spirometer-directed low-dose CT imaging. CT data were analysed using well-evaluated fully quantitative software for bronchiectasis and air trapping (AT)., Results: CT bronchiectasis and AT occurred in 24 % and 58 % of patients, respectively. Of the functional tools, MBW detected the highest rates of abnormality: S cond 82 %, MBW TG RV 78 %, LCI 74 %, MBW TG IC 68 % and S acin 51 %. CPET VO 2 peak detected slightly higher rates of abnormality (9 %) than spirometry-based FEV 1 (2 %). For oscillometry AX (14 %) performed better than Rrs (2 %) whereas Xrs and R5-19 failed to detect any abnormality. LCI and S cond correlated with bronchiectasis (r = 0.55-0.64, p < 0.001) and AT (r = 0.73-0.74, p < 0.001). MBW-assessed trapped gas was detectable in 92 % of subjects and concordant with CT-assessed AT in 74 %., Conclusions: Significant structural and functional deficits occur in early CF lung disease, as detected by CT and MBW. For MBW, additional utility, beyond that offered by LCI, was suggested for S cond and MBW-assessed gas trapping. Our study reinforces the complementary nature of these tools and the limited utility of conventional oscillometry and CPET in this setting., Competing Interests: Declaration of competing interest The authors have no conflict of interests to declare, (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Many children undergo allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of malignant and nonmalignant conditions. Unfortunately, pulmonary complications occur frequently post-HSCT, with bronchiolitis obliterans syndrome (BOS) being the most common noninfectious pulmonary complication. Current international guidelines contain conflicting recommendations regarding post-HSCT surveillance for BOS, and a recent NIH workshop highlighted the need for a standardized approach to post-HSCT monitoring. As such, this guideline provides an evidence-based approach to detection of post-HSCT BOS in children. Methods: A multinational, multidisciplinary panel of experts identified six questions regarding surveillance for, and evaluation of, post-HSCT BOS in children. A systematic review of the literature was undertaken to answer each question. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations addressing the role of screening pulmonary function testing and diagnostic tests in children with suspected post-HSCT BOS were made. Following a Delphi process, new diagnostic criteria for pediatric post-HSCT BOS were also proposed. Conclusions: This document provides an evidence-based approach to the detection of post-HSCT BOS in children while also highlighting considerations for the implementation of each recommendation. Further, the document describes important areas for future research.

Hematopoietic stem cell transplantation (HSCT) is undertaken in children with the aim of curing a range of malignant and nonmalignant conditions. Unfortunately, pulmonary complications, especially bronchiolitis obliterans syndrome (BOS), are significant sources of morbidity and mortality post-HSCT. Currently, criteria developed by a National Institutes of Health (NIH) working group are used to diagnose BOS in children post-HSCT. Unfortunately, during the development of a recent American Thoracic Society (ATS) Clinical Practice Guideline on this topic, it became apparent that the NIH criteria have significant limitations in the pediatric population, leading to late diagnosis of BOS. Specific limitations include use of an outdated pulmonary function testing reference equation, a reliance on spirometry, use of a fixed forced expiratory volume in 1 second (FEV 1 ) threshold, focus on obstructive defects defined by FEV 1 /vital capacity, and failure to acknowledge that BOS and infection can coexist. In this review, we summarize the evidence regarding the limitations of the current criteria. We also suggest potential evidence-based ideas for improving these criteria. Finally, we highlight a new proposed criteria for post-HSCT BOS in children that were developed by the authors of the recently published ATS clinical practice guideline, along with a pathway forward for improving timely diagnosis of BOS in children post-HSCT., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

This clinical practice guideline update provides recommendations for treating breakthrough chemotherapy-induced nausea and vomiting (CINV) and preventing refractory CINV in pediatric patients. Two systematic reviews of randomized controlled trials in adult and pediatric patients informed the recommendations. In patients with breakthrough CINV, escalation of antiemetic agents to those recommended for chemotherapy of the next higher level of emetogenic risk is strongly recommended. A similar recommendation to escalate therapy is made to prevent refractory CINV in patients who did not experience complete breakthrough CINV control and are receiving minimally or low emetogenic chemotherapy. A strong recommendation to use antiemetic agents that controlled breakthrough CINV for the prevention of refractory CINV is also made., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

We recently developed a model-based method for analyzing multiple breath nitrogen washout data that does not require identification of Phase-III. In the present study, we assessed the effect of irregular breathing patterns on the intra-subject variabilities of the model parameters. Nitrogen fraction at the mouth was measured in 18 healthy and 20 asthmatic subjects during triplicate performances of multiple breath nitrogen washout, during controlled (target tidal volume 1 L at 8-12 breaths per minute) and free (unrestricted) breathing. The parameters S cond , S acin and functional residual capacity (FRC) were obtained by conventional analysis of the slope of Phase-III. Fitting the model to the washout data provided functional residual capacity (FRC M ), dead space volume (V D ), the coefficient of variation of regional specific ventilation ([Formula: see text]), and the model equivalent of S acin (S acin-M ). Intra-participant coefficients of variation for the model parameters for both health and asthma were FRC M  < 5.2%, V D  < 5.4%, [Formula: see text] < 9.0%, and S acin-M  < 45.6% for controlled breathing, and FRC M  < 4.6%, V D  < 5.3%, [Formula: see text] < 13.2%, and S acin-M  < 103.2% for free breathing. The coefficients of variation limits for conventional parameters were FRC < 6.1%, with S cond  < 73.6% and S acin  < 49.2% for controlled breathing and S cond  < 35.0% and S acin  < 74.4% for free breathing. The model-fitting approach to multiple breath nitrogen washout analysis provides a measure of regional ventilation heterogeneity in [Formula: see text] that is less affected by irregularities in the breathing pattern than its corresponding Phase-III slope analysis parameter S cond ., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Our objective was to update a clinical practice guideline for the prevention and treatment of Clostridioides difficile infection (CDI) in pediatric patients with cancer and hematopoietic cell transplantation recipients. We reconvened an international multi-disciplinary panel. A systematic review of randomized controlled trials (RCTs) for the prevention or treatment of CDI in any population was updated and identified 31 new RCTs. Strong recommendations were made to use either oral metronidazole or oral vancomycin for non-severe CDI treatment, and to use either oral vancomycin or oral fidaxomicin for severe CDI. A strong recommendation that fecal microbiota transplantation should not be routinely used to treat CDI was also made. The panel made two new good practice statements to follow infection control practices including isolation in patients experiencing CDI, and to minimize systemic antibacterial administration where feasible, especially in patients who have experienced CDI., Competing Interests: BTF has served on a data safety monitoring board for Astellas and BTF's institution has received grant support from Allovir and Pfizer as well as CDC, FDA and NIH for research performed. CD has received support from Abramson Cancer Center K12 and a CIHR Fellowship Award. TL's institution has received an unrestricted research grant by Gilead Sciences and TL has received payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from: Astra Zeneca, EUSA Pharma, Gilead Sciences, MSD/Merck and Pfizer. TL has received support for attending meetings and/or travel from EUSA Pharma and has served on a data safety monitoring board or advisory board for: EUSA Pharma, Gilead Sciences, Merck/MSD, Mundipharma, Pfizer and Pharming. TL has had a leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid at: Working Party Infection German Society of Pediatric Oncology and Hematology and Working Party Infection German Society of Pediatric Infectious Diseases. LS is supported by the Canada Research Chair in Pediatric Oncology Supportive Care. No other authors declared a conflict of interest., (© 2024 The Author(s).)

Background: The primary objective was to measure the proportion of episodes where care delivery was inconsistent with selected recommendations of a clinical practice guideline (CPG) on fever and neutropenia (FN) management. The influence of site size on CPG-inconsistent care delivery, and association between patient outcomes and CPG-inconsistent care were described., Methods: This retrospective, multicenter study included patients less than 21 years old with cancer who were at high risk of poor FN outcomes and were previously enrolled to a Children's Oncology Group (COG) study at participating National Cancer Institute Community Oncology Research Program (NCORP) institutions from January 2014 through December 2015. Patients were randomly selected for chart review by participating sites from a COG-generated list. Care delivered in each episode was adjudicated (CPG-consistent or CPG-inconsistent) against each of five selected recommendations., Results: A total of 107 patients from 22 sites, representing 157 FN episodes, were included. The most common CPG-inconsistent care delivered was omission of pulmonary computerized tomography in patients with persistent FN (60.3%). Of 74 episodes where assessment of four (episodes without persistent FN) or five (episodes with persistent FN) recommendations was possible, CPG-inconsistent care was delivered with respect to at least one recommendation in 63 (85%) episodes. Site size was not associated with CPG-inconsistent care delivery. No statistically significant association between CPG-inconsistent care and fever recurrence was observed., Conclusions: In this cohort of pediatric patients at high risk of poor FN outcomes, CPG-inconsistent care was common. Opportunities to optimize resource stewardship by boosting supportive care CPG implementation are highlighted., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

This clinical practice guideline provides recommendations for preventing acute and delayed phase chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. The recommendations are based on two systematic reviews of randomized controlled trials evaluating interventions to prevent (1) acute phase CINV and (2) delayed phase CINV. Recommendations for acute phase and delayed phase CINV prophylaxis are made for patients receiving chemotherapy of varying emetogenicity, as well as for patients not able to receive dexamethasone or a neurokinin-1 receptor antagonist. Evidence gaps, including antiemetic safety and optimal dosing, were identified., (© 2022 Wiley Periodicals LLC.)

Purpose: While care pathways based upon clinical practice guidelines (CPGs) are important, little is known about optimal approaches to development and adaptation in pediatric oncology. Objectives were to develop care pathway templates for pediatric cancer supportive care that are based upon CPGs and to adapt an infection management care pathway for use at a single institution., Methods: Study phases were as follows: (1) creation of care pathway templates across multiple supportive care topics; (2) refinement of the infection management care pathway template by interviewing pediatric oncology clinicians at a single institution; and (3) adaptation of the infection management care pathway template for use at a different institution., Results: Informed by seven CPGs, an initial iteration of the infection management care pathway template was created. This template was then refined based upon 20 interviews with pediatric oncology clinicians. Adaptation of the infection management care pathway template for use at a different institution required many changes to improve its clinical usability. Specificity and additional information not considered by the source CPGs were incorporated., Conclusion: We developed a process to create care pathway templates across multiple supportive care topics in pediatric oncology and to refine and adapt the infection management care pathway. While we found that the process was feasible, we also identified the need to substantially modify the care pathway during the adaptation process to consider scenarios not addressed by the source CPGs. Future work should measure implementation success., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Multiple breath washout (MBW) is used for early detection of cystic fibrosis (CF) lung disease, with SF 6 MBW commonly viewed as the reference method. The use of N 2 MBW in infants and toddlers has been questioned for technical and physiological reasons, but a new correction of the N 2  signal has minimized the technical part. The present study aimed to assess the remaining differences and the contributing mechanisms for the differences between SF 6 and N 2 MBW,corrected-such as tidal volume reduction during N 2 washout with pure O 2 ., Method: This was a longitudinal multicenter cohort study. SF 6 MBW and N 2 MBW were performed prospectively at three CF centers in the same visits on 154 test occasions across 62 children with CF (mean age: 22.7 months). Offline analysis using identical algorithms to the commercially available program provided outcomes of N 2,original and N 2,corrected for comparison with SF 6 MBW., Results: Mean functional residual capacity, FRC N2,corrected was 14.3% lower than FRC N2, original , and 1.0% different from FRC SF6 . Lung clearance index, LCI N2,corrected was 25.2% lower than LCI N2,original , and 7.3% higher than LCI SF6 . Mean (SD) tidal volume decreased significantly during N 2 MBW corrected , compared to SF 6 MBW (-13.1 ml [-30.7; 4.6], p < 0.0001, equal to -12.0% [-25.7; 1.73]), but this tidal volume reduction did not correlate to the differences between LCI N2,corrected and LCI SF6 . The absolute differences in LCI increased significantly with higher LCI SF6 (0.63/LCI SF6 ) and (0.23/LCI SF6 ), respectively, for N 2,original and N 2,corrected , but the relative differences were stable across disease severity for N 2,corrected , but not for N 2,original ., Conclusion: Only minor residual differences between FRC N2,corrected and FRC SF6 remained to show that the two methods measure gas volumes very similar in this age range. Small differences in LCI were found. Tidal volume reduction during N 2 MBW did not affect differences. The corrected N 2 MBW can now be used with confidence in young children with CF, although not interchangeably with SF 6 ., (© 2022 Wiley Periodicals LLC.)

Landscape fires are increasing in frequency and severity globally. In Australia, extreme bushfires cause a large and increasing health and socioeconomic burden for communities and governments. People with asthma are particularly vulnerable to the effects of landscape fire smoke (LFS) exposure. Here, we present a position statement from the Thoracic Society of Australia and New Zealand. Within this statement we provide a review of the impact of LFS on adults and children with asthma, highlighting the greater impact of LFS on vulnerable groups, particularly older people, pregnant women and Aboriginal and Torres Strait Islander peoples. We also highlight the development of asthma on the background of risk factors (smoking, occupation and atopy). Within this document we present advice for asthma management, smoke mitigation strategies and access to air quality information, that should be implemented during periods of LFS. We promote clinician awareness, and the implementation of public health messaging and preparation, especially for people with asthma., (© 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Background: Cystic fibrosis (CF) lung disease starts in infancy and can be assessed for structural lung abnormalities using computed tomography or magnetic resonance scans, or for lung function impairment using multiple breath washout (MBW). However, in infancy these two methods are not well correlated. Trajectories of CF lung disease assessed by MBW in infants and toddlers remain poorly described, which is why we aimed to 1) describe the trajectory of lung function, 2) explore risk factors for progression and 3) explore the real-life effect of lumacaftor/ivacaftor., Methods: This was a nationwide observational cohort study (2018-2021) using data collected as part of the routine clinical surveillance programme (including MBW and monthly endo-laryngeal suction sampling for bacterial pathogens) in children born after implementation of newborn screening for CF (May 2016). Lumacaftor/ivacaftor commenced from age 2 years in children homozygous for F508del. Ventilation distribution efficiency (VDE), recently described to have advantages over lung clearance index (LCI), was reported as the primary MBW outcome after z-score calculations based on published reference data. Mixed effect linear regression models were the main statistical analyses performed in this study., Results: 59 children, aged 2-45 months, contributed with 211 MBW occasions (median (interquartile range (IQR)) 3 (2-5) MBW occasions per child) with a median (IQR) follow-up time of 10.8 (5.2-22.3) months. An overall mean annual deterioration rate of -0.50 (95% CI -0.78- -0.22) z-VDE was observed, starting from an estimated mean z-VDE of -1.68 (95% CI -2.15- -1.22) at age 0.0 years (intercept). Pseudomonas aeruginosa "ever" (n=14, MBWs 50) had a significantly worse z-VDE trajectory versus P. aeruginosa "never" (mean difference 0.53 (95% CI 0.16-0.89) per year; p=0.0047) and lumacaftor/ivacaftor treatment (n=22, MBWs 46) significantly improved the trajectory of z-VDE (mean difference 1.72 (95% CI 0.79-2.66) per year; p=0.0004), leading to a stable mean z-VDE trajectory after start of treatment., Conclusions: Infants and toddlers with CF demonstrated progressive deterioration in z-VDE over the first years of life. P. aeruginosa isolation "ever" was associated with an accelerated deterioration in lung function, while lumacaftor/ivacaftor therapy significantly improved and stabilised the trajectory., Competing Interests: Conflict of interest: None of the authors have personal financial relationships with any organisations that might have an interest in the submitted work., (Copyright ©The authors 2023.)

Following discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 and subsequent elucidation of the varied CFTR protein abnormalities that result, a new era of cystic fibrosis management has emerged-one in which scientific principles translated from the bench to the bedside have enabled us to potentially treat the basic defect in the majority of children and adults with cystic fibrosis, with a resultant burgeoning adult cystic fibrosis population. However, the long-term effects of these therapies on the multiple manifestations of cystic fibrosis are still under investigation. Understanding the effects of modulators in populations excluded from clinical trials is also crucial. Furthermore, establishing appropriate disease measures to assess efficacy in the youngest potential trial participants and in those whose post-modulator lung function is in the typical range for people without chronic lung disease is essential for continued drug development. Finally, recognising that a health outcome gap has been created for some people and widened for others who are not eligible for, cannot tolerate, or do not have access to modulators is important., Competing Interests: Declaration of interests In the last 36 months, unrelated to this work, JLT-C has received grants to her institution from the Cystic Fibrosis Foundation (CFF), the National Institutes of Health, Vertex Pharmaceuticals, Eloxx, and 4DMT; she has received fees from Vertex Pharmaceuticals related to consultation on clinical research design, participation on advisory boards, and speaking engagements; and has served on advisory boards or provided clinical trial design consultation for Insmed, 4DMT, and AbbVie. JLT-C has served as chair of a data monitoring committee for AbbVie. She serves as the adult patient care representative to the CFF board of trustees, and on the CFF's clinical research executive committee, clinical research advisory board, as immediate past chair of the Cystic Fibrosis Therapeutics Development Network's Sexual Health, Reproduction and Gender Research working group, and as co-chair of the Heath Equity Team Science Awards study section. She also serves on the scientific advisory board for Emily's Entourage, on the American Thoracis Society Respiratory Health Awards Working Group, and as chair-elect of the International Conference Committee. She is an associate editor for the Journal of Cystic Fibrosis and a member of the international advisory board for The Lancet Respiratory Medicine. She serves on the Clinical Trials Review (CTLR) Study section for the National Institutes of Health National Heart, Lung, and Blood Institute. PDR reports that his previous institution, The Children's Hospital at Westmead, Sydney, has received remuneration for services provided by the Australian Central Over-Reading Centre he established for pharmaceutical-sponsored and investigator-led studies in cystic fibrosis. This renumeration will also be the case for his current institution (the University of Queensland) moving forward. MS has received grants and research support from: GSK, Insmed, Novartis, Trudell Pharma, Tel Aviv League for Lung Diseases; consultation fees from AstraZeneca, Boehringer Ingelheim, Dexcel, GSK, Kamada, Syncrony Medical, Trumed, Zambon; and speaker's fees from AstraZeneca, Boeringer Ingelheim, GSK, Kamada, Novartis, PhysioAssist, Sanofi, and Teva. MS serves as a data and safety monitoring board member for Bonus Biotherapeutics. MS is a member of management board of EMBARC, a member of the executive committee of the Israel Society for TB and Mycobacterial Diseases, an associate editor for the American Journal of Respiratory and Critical Care Medicine, and an editorial board member for the European Respiratory Journal and Chest. DGD reports grants from Chiesi Farmaceutici, the CF Trust, and the CFF to his institution. He reports consulting fees from Vertex and Insmed; and payments from Chiesi and Gilead for presentations. DGD receives support from the European Cystic Fibrosis Society and CFF for travel to meetings. He participates on a data and safety monitoring board for the Nomab trial and CSL Behring. He serves on the research oversight scientific board for the UK Clinical Trials Accelerator Platform and is the Director of the European Cystic Fibrosis Society Clinical Trials Network., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Children with cancer commonly experience distressing symptoms such as pain, fatigue and nausea. Improvements in patient outcomes have been associated with implementation of clinical practice guideline-consistent care across several domains. The objective of this study was to develop a process to identify symptom management clinical practice guidelines (CPGs) applicable to children and adolescents receiving cancer treatments., Methods: We focused on identifying CPGs to manage 15 symptoms. The process defined three Tiers of CPGs based upon applicability to pediatric cancer patients and ease of identification: Tier 1: endorsed by the Children's Oncology Group; Tier 2: housed in the Emergency Care Research Institute repository, or developed by the American Society of Clinical Oncology or National Institute for Health and Care Excellence; and Tier 3: identified by systematic review. We first searched for CPGs published 2015-2020 and identified Tiers 1 or 2 CPGs. If unavailable or scope was too narrow, we proceeded to Tier 3. If CPGs were not identified, we repeated these steps for CPGs published 2010-2014., Results: There were six Tier 1 and 13 Tier 2 CPGs published 2015-2020 across the 15 symptoms. Four symptoms required progression to Tier 3 because CPGs were absent (anger) or because scope was too narrow (pain, anorexia/excessive hunger and diarrhea). The systematic review identified three CPGs for pain and none for the other three symptoms. In total, CPGs were identified for 14 of 15 symptoms. None were identified for anger., Conclusion: We created a process to identify supportive care CPGs for pediatric cancer symptom management and were able to identify CPGs that addressed 14 of 15 symptoms. Future work should focus on evaluating implementation techniques for these CPGs and determining the impact of these CPGs on provider and patient outcomes., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective was to update a clinical practice guideline (CPG) for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients. We reconvened a multi-disciplinary and multi-national panel. While the previous 2018 CPG evaluated adult and pediatric randomized controlled trials (RCTs) to manage fatigue, this 2023 update revised previous recommendations based only on pediatric RCTs. Twenty RCTs were included in the updated systematic review. Physical activity significantly reduced fatigue (standardized mean difference -0.44, 95% confidence interval -0.64 to -0.24; n = 8 RCTs). Using the 2018 recommendations as a basis, the panel continued to make strong recommendations to use physical activity, and to offer relaxation, mindfulness or both, to manage fatigue in pediatric patients. Cognitive or cognitive behavioral therapies may be offered. Pharmacological approaches should not be routinely used. The panel made a new good practice statement to routinely assess for fatigue, ideally using a validated scale., Competing Interests: PSH received grants or research support from NIH; royalties or licenses from Lippincott; consulting fees from MSKCC and participated on the REACH Board at Nemours, Delaware. SNCR received grants from CIHR, CCS and Kids Cancer Care-IMPACT. LS is supported by the Canada Research Chair in Pediatric Oncology Supportive Care. No other authors declared a conflict of interest., (© 2023 The Author(s).)

Mycobacterium abscessus is a nontuberculous mycobacterium (NTM) of particular concern in individuals with obstructive lung diseases such as cystic fibrosis (CF). Treatment requires multiple drugs and is characterised by high rates of relapse; thus, new strategies to limit infection are urgently required. This study sought to determine how Bacille Calmette-Guérin (BCG) vaccination may impact NTM infection, using a murine model of Mycobacterium abscessus infection and observational data from a non-BCG vaccinated CF cohort in Sydney, Australia and a BCG-vaccinated CF cohort in Cape Town, South Africa. In mice, BCG vaccination induced multifunctional antigen-specific CD4 + T cells circulating in the blood and was protective against dissemination of bacteria to the spleen. Prior infection with M. abscessus afforded the highest level of protection against M. abscessus challenge in the lung, and immunity was characterised by a greater frequency of pulmonary cytokine-secreting CD4 + T cells compared to BCG vaccination. In the clinical CF cohorts, the overall rates of NTM sampling during a three-year period were equivalent; however, rates of NTM colonisation were significantly lower in the BCG-vaccinated (Cape Town) cohort, which was most apparent for M. abscessus . This study provides evidence that routine BCG vaccination may reduce M. abscessus colonisation in individuals with CF, which correlates with the ability of BCG to induce multifunctional CD4 + T cells recognising M. abscessus in a murine model. Further research is needed to determine the optimal strategies for limiting NTM infections in individuals with CF.

Pulmonary chronic graft- versus -host disease (cGVHD) is a substantial cause of pulmonary morbidity and mortality post-haematopoietic stem cell transplantation (HSCT). Current spirometry-based monitoring strategies have significant limitations. Understanding the utility of novel peripheral airway function tests - multiple breath washout (MBW) and oscillometry - is critical in efforts to improve detection, facilitate earlier intervention and improve outcomes. In this scoping review, we identified 17 studies investigating MBW or oscillometry, or both, after allogenic HSCT. Despite small study numbers limiting the ability to draw firm conclusions, several themes were evident. Detectable peripheral airway abnormality in MBW occurred in a substantial proportion prior to HSCT. MBW indices post-HSCT were more frequently abnormal than spirometry when reporting group data and among those with extrapulmonary cGVHD and pulmonary cGVHD. Changes in MBW indices over time may be more indicative of pulmonary complications than absolute values at any given time point. Oscillometry indices were often normal at baseline, but more frequently abnormal in those who developed pulmonary cGVHD. Pooling currently available individual participant data across these studies may improve our ability to formally compare their respective sensitivity and specificity at specific time points and assess the trajectory of MBW and oscillometry indices over time., Competing Interests: Conflict of interest: N. Sonneveld has nothing to disclose. Conflict of interest: J.H. Rayment has nothing to disclose. Conflict of interest: J. Usemann has nothing to disclose. Conflict of interest: K.G. Nielsen has nothing to disclose. Conflict of interest: P.D. Robinson has nothing to disclose., (Copyright ©The authors 2023.)

Haemoptysis occurs in up to 25 % of young people with Cystic fibrosis (CF) [1]. We undertook a literature review and described the management approach to haemoptysis in CF between 2010 and 2020 at an Australian tertiary paediatric centre, The Children's Hospital Westmead, Sydney, New South Wales, using a retrospective review of the medical records which identified 67 episodes. Sixty episodes met inclusion criteria, including 31 patients. Using the US CF Foundation guidelines, episodes were classified as scant (53.3 %), moderate (38.3 %) or massive (8.3 %). Fifty-two percent of patients were female, mean age at presentation was 15.4 years (SD+/- 2.4) and 58 % were homozygous for the Fdel508 genotype. Twelve episodes (9 patients) required bronchial artery embolization (BAE). BAE was used in all cases of massive haemoptysis 5/5 (100 %), 6/23 (22 %) episodes of moderate and 1/32 (3 %) episode of scant haemoptysis as an elective procedure for recurrent haemoptysis. Our literature review and institutional experience highlights the need for up-to-date management guidelines in the management of haemoptysis in Cystic Fibrosis. Based on our experience, we provide a proposed algorithm to help guide the management of haemoptysis in CF., Competing Interests: Conflict of Interest The authors have no conflict of interest to disclose., (Copyright © 2022. Published by Elsevier Ltd.)

This 2021 clinical practice guideline update provides recommendations for preventing anticipatory chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. Recommendations are based on systematic reviews that identified (1) if a history of acute or delayed CINV is a risk factor for anticipatory CINV, and (2) interventions for anticipatory CINV prevention and treatment. A strong recommendation to optimize acute and delayed CINV control in order to prevent anticipatory CINV is made. Conditional recommendations are made for hypnosis, systematic desensitization, relaxation techniques, and lorazepam for the secondary prevention of anticipatory CINV. No recommendation for the treatment of anticipatory CINV can be made., (© 2021 Wiley Periodicals LLC.)

Sensor errors resulting in elevated values of N 2 concentration [N 2 ] in commercial multiple-breath washout (MBW) devices have been shown to prolong the washout and result in erroneously high functional residual capacity (FRC) and lung clearance index (LCI) values. The errors also affect the indices of conductive and acinar ventilatory heterogeneity ( S cond and S acin ) although the mechanism by which this change in values occurs remains unclear. Exploring these effects also provides a timely opportunity to examine the appropriateness of the algorithm used to calculate these indices. Using a two-compartment model with differing specific ventilation (SV) such that the lower SV unit empties late, noise-free MBW were simulated both corrected and uncorrected for the recent sensor error. S cond was calculated using regression of normalized phase III slope (Sn III ) against lung turnover (TO) from a TO range starting at 1.5 and ending at an upper turnover (TO upper ) between 4 and 8 (default 6) over a range of simulated values. The principal effect of the sensor error was that as the MBW proceeded the phase III slope of successive breaths was normalized by an increasingly overestimated [N 2 ], resulting in Sn III values that fell precipitously at high TO, greatly reducing S cond . Reanalysis of previously published data and of simulated data showed a large proportional bias in S cond , whereas S acin was only minimally affected. In adult subject data, reducing TO upper below 5.5 was associated with a large drop of up to ∼60% in S cond calculated from data corrected for sensor error. Raising the upper TO limit elevated S cond by ∼20% but with a large concomitant increase in variability. In contrast to S cond , S acin was relatively unaffected by changes in TO upper with changes of <3%. This work serves to emphasize that the upper limit of TO of 6 represents an appropriate upper limit for the calculation of S cond . NEW & NOTEWORTHY Sensor errors that elevated values of N 2 concentration in commercial multiple-breath washout (MBW) devices resulted in errors in calculated parameters including S cond and S acin . We examined the mechanism of the change in values produced by these errors and explored the appropriateness of the calculation of S cond and S acin . This work serves to emphasize that the current algorithm in use is appropriate for the calculation of S cond and S acin .

Purpose: To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients., Methods: The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients. Using the Grading of Recommendations Assessment, Development and Evaluation framework, evidence quality was classified as high, moderate, low, or very low. The panel updated recommendations related to initial management, ongoing management, and empiric antifungal therapy. Changes from the 2017 CPG were articulated, and good practice statements were considered., Results: We identified 10 new RCTs in addition to the 69 RCTs identified in previous FN CPGs to inform the 2023 FN CPG. Changes from the 2017 CPG included two conditional recommendations regarding (1) discontinuation of empiric antibacterial therapy in clinically well and afebrile patients with low-risk FN if blood cultures remain negative at 48 hours despite no evidence of marrow recovery and (2) pre-emptive antifungal therapy for invasive fungal disease in high-risk patients not receiving antimold prophylaxis. The panel created a good practice statement to initiate FN CPG-consistent empiric antibacterial therapy as soon as possible in clinically unstable febrile patients., Conclusion: The updated FN CPG incorporates important modifications on the basis of recently published trials. Future work should focus on addressing knowledge gaps, improving CPG implementation, and measuring the impact of CPG-consistent care.

A systematic review was undertaken to describe dexamethasone doses studied for chemotherapy-induced vomiting (CIV) prophylaxis in pediatric patients and their effects on achieving complete acute CIV control. No dose-finding studies were identified. However, 16 studies assessing pediatric patients who received dexamethasone were included and classified according to the emetogenicity of chemotherapy administered. Eight different total daily dexamethasone doses were administered to patients on day 1 of highly emetogenic chemotherapy: three in conjunction with aprepitant/fosaprepitant plus a 5HT 3 antagonist and five in conjunction with a 5HT 3 antagonist. Five different total daily dexamethasone doses were administered in conjunction with a 5HT 3 antagonist to patients on day 1 of moderately emetogenic chemotherapy. Due to the heterogeneity of studies identified, meta-analysis was not possible. The optimal dexamethasone dose to control acute CIV and to minimize harms in pediatric patients remains uncertain. This is a key area for future research., (© 2020 Wiley Periodicals LLC.)