OBJECTIVE:In 2024, brand-name Flovent (fluticasone propionate), the most widely prescribed inhaled corticosteroid (ICS) in the United States, was discontinued, eliminating a key treatment option for pediatric asthma. There have yet to be reports describing pediatric clinicians' experiences with this abrupt loss of a mainstay therapy for one of the most common chronic diseases in children. The study aimed to examine the experience of pediatric clinicians with the discontinuation of Flovent for asthma management. METHODS:A web-based survey was disseminated via pediatric and pediatric pulmonary networks, both regionally and nationally, to pediatric primary care and subspecialty physicians and advanced practice practitioners. The survey assessed clinician awareness, preparedness, and the clinical impact of Flovent discontinuation. RESULTS:Among 226 respondents, 71% were aware of the Flovent discontinuation in advance; however, 79% felt unprepared or very unprepared once it went into effect. Clinicians reported significant disruptions in prescribing and clinical workflow, with 56% describing the impact on their practice as severe. Factors most frequently cited as causing moderate or severe burden included prescribing alternate ICS therapy, including insurance authorization requirements (90%), pharmacy shortages (85%), and difficulty finding age-appropriate alternatives (82%). In free-text responses, clinicians described perceived worsening asthma control and increased acute healthcare utilization following the discontinuation, particularly among younger patients. CONCLUSIONS:Pediatric clinicians who care for children with asthma reported significant disruptions to patient care following the discontinuation of Flovent. These findings underscore the need for systems-level support of clinicians during major formulary transitions to minimize disruptions, particularly within pediatric asthma.

Sickle cell disease (SCD) is a globally prevalent inherited hemoglobinopathy marked by chronic hemolysis, vaso-occlusion, and systemic inflammation, leading to significant acute and chronic complications. Acute chest syndrome (ACS), a leading cause of morbidity and mortality in people with SCD (pwSCD) is often associated with vaso-occlusive pain episodes (VOE). Despite its clinical significance, the pathogenesis of ACS remains incompletely understood. This review synthesizes current knowledge on ACS in SCD, highlighting known and emerging risk factors, evolving concepts in pathophysiologic causes, current diagnostic and phenotyping challenges, and discusses new approaches to preventative and therapeutic treatment regimens. We describe the significant disparities in care and outcomes in low- and middle-income countries (LMIC), emphasizing the need for improved access to multidisciplinary subspecialty SCD care, including newborn screening and access to therapeutics. Finally, we identify key research gaps that need to be addressed to advance our understanding and management of ACS in a diverse healthcare landscape. Overall, this review aims to inform clinical practice and guide future research toward reducing the burden of ACS in pwSCD across the globe. Ultimately, advancing ACS management requires a paradigm shift toward resource-adaptable, precision-based care.

Respiratory health is the result of genetics and socioenvironmental factors that influence optimal lung development and function. Adverse socioenvironmental exposures are linked with pediatric respiratory diseases. Because pulmonary symptomatology is nonspecific, objective assessment of respiratory health is based on pulmonary function testing. Historically, pulmonary function testing was adjusted for race. With increased recognition of race being a social rather than a biological construct, the American Thoracic Society issued guidelines in 2023 recommending a "race-neutral" approach to the interpretation of lung function, as put forth by the Global Lung Function Initiative-Global equations. Using disease examples of asthma and pulmonary involvement in sickle cell disease, we describe effects of these guidelines on disease reclassification, including identification of worse airflow obstruction in Black children, that corresponded with disease burden. Despite the greater alignment of the race-neutral approach with disease burden, there is a possibility that reclassifying disease may widen the racial gaps. For these reasons, although we recommend clinicians to routinely incorporate spirometry for assessment of respiratory disease, we suggest that in the setting of an abnormal result, they not only address the underlying disease but also assess for, and address, adverse socioenvironmental factors that are known determinants of low lung function. This contextual analysis of pulmonary function is key in providing equitable respiratory health for all children. The recommendations also identify the need for additional research on its implications among healthy children and the role of biological variables such as genetic variation that are associated with ancestry and independently associated with lower lung function.

BACKGROUND:In 2017 Boston Medical Center's (BMC) general pediatric inpatient unit implemented bi-level positive airway pressure (BiPAP) as supportive noninvasive ventilation for acute chest syndrome prevention (SNAP) to prevent adverse respiratory outcomes among medically stable, hospitalized patients with sickle cell disease. Barriers and facilitators to SNAP implementation at BMC differ from those in other settings. OBJECTIVE:To examine contextual determinants of SNAP implementation across different settings. METHODS:We conducted semi-structured interviews with inpatient clinicians at three sites (Site 1: extensive implementation, Site 2: limited implementation, Site 3: not implemented) about factors that would affect SNAP implementation. Interviews and analysis were guided by the Promoting Action on Research Implementation in Health Services (PARiHS) framework. RESULTS:We interviewed 29 healthcare workers (physicians, nurses, physician assistants, child life specialists, respiratory therapists and psychologists). Five major themes emerged: (1) Communication between staff, particularly between the night and day shift, is critical for BiPAP initiation and success. (2) Nurses are key to successful SNAP implementation. (3) SNAP implementation requires multidisciplinary support, including integration of respiratory therapists and child life. (4) Individual unit level size, culture and workflow influence implementation (5) Hospital resources and leadership support are important for SNAP implementation. CONCLUSIONS:Successful SNAP implementation across different contexts will require optimized communication between healthcare team members and the integration of respiratory therapy and child life early in the process of BiPAP initiation. Adapting to the unique features of each institution will be critical.

Mepolizumab (anti-IL5 therapy) reduces asthma exacerbations in urban children with exacerbation-prone eosinophilic asthma. We previously utilized nasal transcriptomics to identify inflammatory pathways (gene co-expression modules) associated with asthma exacerbations despite this therapy. In this study, we applied differential gene correlation analysis on these targeted gene co-expression modules to gain better insight into the treatment effects on correlation structure within gene networks. Mepolizumab treatment resulted in loss of correlation amongst eosinophil-specific genes but conservation and even strengthening of correlation amongst mast cell-specific genes, T2 cytokines, and airway epithelial inflammatory genes. Notably, mepolizumab induced significant gain in correlation of genes associated with multiple aspects of airway epithelial inflammation including those related to extracellular matrix production and nitric oxide synthesis, and this change was associated with a poor clinical response to mepolizumab. These findings highlight that using differential gene correlation analysis offers insight into the molecular regulatory effects of treatment on gene interactions and may lead to better understanding of disease mechanisms and therapeutic responses. ClinicalTrials.gov ID: NCT03292588.

BACKGROUND:Randomised controlled studies evaluating vitamin D supplementation in pregnancy or early childhood for preventing childhood asthma have yielded inconclusive results. Previous systematic reviews of vitamin D for asthma prevention focused on studies comparing vitamin D to placebo or studies intervening in pregnancy, limiting the body of evidence. OBJECTIVES:Primary: to evaluate the efficacy of any vitamin D supplementation and high-dose vitamin D supplementation in early life, including the prenatal period, for preventing asthma in children. Secondary: to assess the efficacy of vitamin D supplementation: • for preventing asthma in children at risk of vitamin D deficiency at the start of the trial or whose mothers were at risk; • by intervention timing and the cumulative dose administered; • in preventing factors associated with early childhood asthma, including atopic dermatitis, respiratory tract infections, sensitisation to allergens, and airway inflammation. SEARCH METHODS:We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the International Clinical Trials Registry Platform, and the Cochrane Airways and Skin Trial Registers. We checked the reference lists of relevant systematic reviews and meta-analyses. We contacted authors to obtain additional study information as needed. Date of last search: October 2023. SELECTION CRITERIA:We included randomised controlled studies comparing higher versus lower/standard dose vitamin D (≤ 400 international units (IU)/day) or any vitamin D versus placebo/no treatment in generally healthy pregnant or lactating women or children up to five years of age that evaluated childhood asthma, wheeze, atopic dermatitis, airway infections, allergic sensitisation, and airway inflammation. We excluded trials recruiting populations with pre-existing conditions. DATA COLLECTION AND ANALYSIS:We followed standard Cochrane methodological procedures, including using Cochrane's Screen4Me workflow. We considered participants rather than events as the unit of analysis, performed fixed-effect meta-analysis, and reported risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) for four comparisons: (1) any vitamin D versus placebo/no supplementation in pregnant or breastfeeding women; (2) any vitamin D versus placebo/no supplementation in infants or children; (3) high versus low/standard dose vitamin D in pregnant or breastfeeding women; (4) high versus low/standard dose vitamin D in infants or children. Our outcomes were: asthma, wheeze, atopic dermatitis, airway infections, allergic sensitisation, airway inflammation, and adverse events. We narratively described results that could not be meta-analysed. We used the Cochrane risk of bias tool (RoB) to assess bias in the studies. We used GRADE to assess the certainty of the evidence. MAIN RESULTS:We included 18 studies involving a total of 10,611 participants, of which 16 contributed data to meta-analyses. Studies were conducted around the world, with most taking place in higher-income countries. The dose and frequency of vitamin D ranged from 200 IU/day to 100,000 IU bolus quarterly, and the duration of supplementation ranged from 28 days to two years. Comparison 1. Any vitamin D versus placebo/no supplementation in pregnant or breastfeeding women (4 studies) Compared to placebo or no supplementation, any vitamin D given to pregnant or breastfeeding women may reduce the risk of early childhood asthma (RR 0.17, 95% CI 0.05 to 0.61; 1 study, 236 participants; low-certainty evidence) and likely has little to no effect on childhood airway infections (RR 1.00, 95% CI 0.97 to 1.04; 3 studies, 1564 participants; moderate-certainty evidence). The evidence is very uncertain for wheeze, atopic dermatitis, allergic sensitisation, airway inflammation, or adverse events. Comparison 2. Any vitamin D versus placebo/no supplementation in infants or children (5 studies) Compared to placebo or no supplementation, any vitamin D given to infants or children may have little to no effect on childhood wheeze (RR 0.89, 95% CI 0.68 to 1.16; 2 studies, 431 participants; low-certainty evidence), atopic dermatitis (RR 1.01, 95% CI 0.80 to 1.28; 2 studies, 448 participants; low-certainty evidence), airway infections (RR 0.92, 95% CI 0.83 to 1.01; 2 studies, 500 participants; low-certainty evidence), allergic sensitisation (RR 2.25, 95% CI 0.60 to 8.50; 1 study, 228 participants; low-certainty evidence), or airway inflammation measured by eosinophil counts (RR 1.06, 95% CI 0.65 to 1.74; 1 study, 226 participants; low-certainty evidence). The evidence is very uncertain for asthma and adverse events. Comparison 3. High versus low/standard dose vitamin D in pregnant or breastfeeding women (4 studies) Compared to low/standard dose, high-dose vitamin D given to pregnant or breastfeeding women likely reduces the risk of childhood wheeze (RR 0.79, 95% CI 0.64 to 0.98; 3 studies, 1439 participants; moderate-certainty evidence), but likely results in little to no difference in childhood asthma, although the direction and magnitude of effect is similar to that for wheeze (RR 0.81, 95% CI 0.63 to 1.04; 2 studies, 1355 participants; moderate-certainty evidence). Compared to low/standard dose, high-dose vitamin D in pregnancy likely has little to no effect on childhood atopic dermatitis (RR 0.91, 95% CI 0.75 to 1.11; 3 studies, 1439 participants; moderate-certainty evidence), airway infections (RR 0.95, 95% CI 0.82 to 1.11; 3 studies, 1441 participants; moderate-certainty evidence), or allergic sensitisation (RR 1.01, 95% CI 0.87 to 1.18; 2 studies, 1110 participants; moderate-certainty evidence). The evidence is very uncertain for adverse events. No studies evaluated airway inflammation. Comparison 4. High versus low/standard dose vitamin D in infants or children (7 studies) Compared to low/standard dose, high-dose vitamin D given to infants or children may slightly reduce airway infections (RR 0.94, 95% CI 0.90 to 0.98; 6 studies, 2385 participants; low-certainty evidence) but may have little to no effect on atopic dermatitis (RR 0.76, 95% CI 0.55 to 1.05; 1 study, 769 participants; low-certainty evidence). The evidence is very uncertain for asthma, wheeze, allergic sensitisation, and adverse events. No studies evaluated airway inflammation. AUTHORS' CONCLUSIONS:Evidence supporting a protective effect of vitamin D supplementation in early life, including the prenatal period, on childhood asthma is limited. Moderate-certainty evidence suggests that high-dose vitamin D in pregnancy likely helps prevent childhood wheeze. Evidence for the effects of vitamin D in early childhood on asthma or wheeze is less certain. Additional high-quality studies, especially in infants and children, are needed to establish with any certainty the effects of vitamin D supplementation on childhood asthma and associated factors.

Rationale: Systemic corticosteroids are standard-of-care treatment for asthma exacerbations; however, little is known about whether corticosteroid effects on airway inflammatory pathways differ when added to biologic therapies targeting type 2 inflammation. Methods: 290 urban children (6-17 years) with exacerbation-prone eosinophilic asthma were randomized (1:1) to q4 week placebo or mepolizumab injections added to guideline-based care for 52 weeks. Nasal lavage samples were collected at baseline (before treatment), post-exacerbation (5-10 days after starting systemic corticosteroids), and on treatment for RNA-sequencing. Differentially expressed genes (DEGs) were assessed using mixed effects modeling (significance threshold FDR<0.05). Results: 98 participants were evaluated following 170 exacerbation events (placebo:105, mepolizumab:65). In the placebo group, there were no significant differentially expressed genes comparing on treatment to before treatment timepoints. In the placebo group, there were 6363 significant DEGs (2734 increased, 3629 decreased) comparing post-exacerbation to on treatment. In the mepolizumab group, there were 1404 significant DEGs (664 increased, 740 decreased) comparing on treatment to before treatment (Fig1A: x-axis). In the mepolizumab group, there were 1111 significant DEGs (413 increased, 698 decreased) comparing post-exacerbation to on treatment (Figure 1A: y-axis). In the post-exacerbation versus on treatment contrasts, there were 885 overlapping significant DEGs (348 increased, 537 decreased) between the placebo and mepolizumab participants. Mepolizumab reduced expression of eosinophil-associated genes (CCL23, GATA1, CLC, PRSS33, PTGDR2, ADORA3, THBS4) on treatment, with a larger decrease post-corticosteroid (more reduced than placebo) (FDR<0.05) (Fig1B). Mepolizumab did not significantly alter expression of mast cell/T2 cytokine-related genes (HDC, CPA3, GATA2, TPSAB2, IL5, IL13, IL1RL1, ALOX15) on treatment; however, expression of these genes significantly decreased post-corticosteroid (more reduced than placebo) (FDR<0.05) (Fig1B). Mepolizumab increased expression of genes associated with epithelial and airway inflammation (CFTR, ERBB2, BMP3, TRPV4) on treatment; however, expression of these genes returned to baseline levels post-corticosteroid (FDR<0.05) (Fig1B). Conclusions: By comparing differential gene expression across treatment groups and time points, we identified overlapping DEGs related to systemic corticosteroid effects, DEGs related only to mepolizumab treatment, and clusters of functionally related genes with additive effects of mepolizumab plus systemic corticosteroids. Mepolizumab enhances the actions of oral corticosteroids on eosinophil related pathways in relation to exacerbations. Oral corticosteroids provide the added benefit of down-regulating mast cell and T2 cytokine pathways. Finally, oral corticosteroids reverse the up-regulation of epithelial inflammatory pathways that occurred during mepolizumab treatment.

BACKGROUND:Standardized acute care asthma pathways are associated with improved asthma outcomes in emergency department and inpatients settings. We developed and implemented an ambulatory acute asthma care pathway (the "Pathway") in the pediatric primary care clinic of our academic safety-net hospital. OBJECTIVE:To qualitatively assess perceived benefits, disadvantages, facilitators, and barriers associated with use and implementation of this Pathway among pediatric primary care providers. METHODS:We conducted semi-structured interviews with primary care providers to elicit their perspectives about the Pathway. The interview guide, codebook, and analysis were guided by the Promoting Action Research on Implementation in Health Services (PARiHS) framework. Interviews were analyzed to identify themes and subthemes. RESULTS:Participants included 13 clinicians (attending physicians, nurse practitioners, and resident trainees). Major themes included: (1) Providers appreciate standardization of care facilitated by the Pathway and perceive the Pathway as promoting evidence-based care; (2) providers' experience managing acute asthma and with electronic order sets affects the way they engage with the Pathway; more data about performance measures would help; (3) the clinical context influences the way providers utilize the Pathway; and (4) providers identified successes of Pathway implementation (i.e. provider meeting presentations, in-clinic support from Asthma Team "champions") as well as opportunities for improvement. CONCLUSIONS:Providers report positive experiences with the Pathway and recognize the benefits of standardized, evidence-based care. Increased feedback about performance and outcomes and strategies to improve usability were proposed as opportunities for optimizing Pathway uptake. Future studies will evaluate the impact of the Pathway on improving clinical outcomes.

Sickle cell anemia (SCA) leads to reduced physical functioning and cardiopulmonary fitness. Prior studies suggest that airway hyperresponsiveness to bronchoprovocation testing is common in SCA, but the prevalence of exercise-induced bronchospasm (EIB) is understudied. We hypothesized that EIB is more common in children with SCA than in controls. Non-asthmatic subjects 10-21 years old with SCA and race-matched controls underwent (1) maximal Cardiopulmonary Exercise Testing (CPET) by cycle ergometry and (2) a Controlled Intensity Interval Test (CIIT) consisting of eight bouts of constant workload cycling, randomized to 50% (moderate) or 70% (vigorous) of peak workload. Spirometry was performed pre/post CPET and CIIT. Multivariable logistic regression models tested associations between SCA status and EIB in response to CPET and CIIT. Compared to controls, subjects with SCA demonstrated lower hemoglobin, reduced baseline spirometry values, and decreased CPET maximal workload. Baseline lower airway obstruction and completion rates for CPET and CIIT were similar between groups. No adverse events occurred. The percentage of participants who met criteria for EIB did not differ between subjects and controls after CPET (21% vs. 26%, p = 0.537) or CIIT (32% vs. 17%, p = 0.126). In adjusted models, SCA status was not associated with EIB after CPET or CIIT. EIB was not more common in subjects with SCA versus controls after maximal CPET or submaximal exercise challenge of longer duration. Further research is needed to inform the development of exercise guidelines and to better understand the effects of exercise on airway dynamics in SCA. Trial Registration: ClinicalTrials.gov identifier: NCT03653676.

PURPOSE:The effects of in-home environmental exposures (IHEEs) on asthma are challenging to examine in populations because information on asthma triggers is usually absent. We leveraged data from electronic health records (EHRs) to investigate the associations of residential cockroach and rodent exposures with lung function among children with asthma. METHODS:We merged clinical pulmonary function test data from EHRs for children with asthma from a large safety net hospital in the Northeast United States with publicly available geospatial data matched to patient addresses. Predicted presence of key IHEE asthma triggers, cockroaches and rodents, were included as main exposures and housing parcel features and census tract characteristics were included as potential confounders in a sensitivity analysis. We fit latent Bayesian hierarchical models of percent predicted forced expiratory volume in one second (FEV1%). RESULTS:The study population of 1070 children had a mean age of 10.2 years and 75 % identified as Black, many living in historically segregated neighborhoods. In models adjusted for individual characteristics, we observed 2.26 (95 % credible interval, 95 %CrI: - 3.72, - 0.79) and 2.58 (95 %CrI: - 4.54, - 0.66) percentage points (pp) lower FEV1% from a one-unit increase in the log-odds of the probability of cockroach and rodent presence, respectively. The association with lung function increased in magnitude for cockroach exposure but attenuated for rodent exposure in sensitivity analyses. CONCLUSIONS:IHEEs were associated with worse lung function among children with asthma in a safety net population. The observed associations underscore how injustices in housing and neighborhood characteristics contribute to asthma morbidity.

Background and ObjectivesThe SARS-CoV-2 pandemic shifted medical training programs to utilize virtual interviews (VIs) starting with the 2020 interview cycle. Fellowship interviews continue in the virtual format. It is unknown how this shift has affected equity for applicants as compared to in-person interviews. Equity in this study includes consideration of the opportunity for an applicant to accept, access, and conduct a VI. This study assessed pediatric pulmonary fellows' perception of equity associated with VIs and preferences for future cycles.MethodsAn anonymous survey link was emailed to Pediatric Pulmonology Program Directors to disseminate to incoming and first-year pediatric pulmonary fellows who participated in the 2022-2023 and 2021-2022 VI seasons. Responses were summarized by frequency and percentages. Inductive coding was used to thematically analyze free-text responses.ResultsNearly 30% of eligible incoming and first-year pulmonary fellows (n = 35/119, 29.4%) completed the survey. Seventy-four percent felt that VIs reduce inequities as compared to in-person interviews. Sixty percent felt that VIs were the most equitable format, and 51% chose a VI as their preferred future format. Important practice considerations to promote equity for future VIs included providing applicants with instruction for the expected dress code, followed by providing applicants with virtual technology (91% and 89% of respondents ranked as at least "somewhat important," respectively).ConclusionVIs were perceived as a more equitable interview format by pediatric pulmonology fellows compared to in-person interviews in our study. To increase equity for VIs, program directors can consider additional adaptations such as providing standardized instruction for dress code and providing the required technology.

FOR RELATED ARTICLE, SEE PAGE 150Sickle cell disease (SCD) is a common, life-limiting genetic hemoglobinopathy that affects 300,000 live births per year worldwide. Acute chest syndrome (ACS) can be a severe and potentially fatal acute SCD complication. In the largest cohort study undertaken to investigate potential causes for ACS (which was published more than 20 years ago), no cause was identified in nearly one-half of all episodes.1Vichinsky E. Neumayr L. Earles A. Causes and outcomes of acute chest syndrome in sickle cell disease.N Engl J Med. 2000; 342: 1855-1866Crossref PubMed Scopus (955) Google Scholar That said, approximately one in three ACS cases with an identifiable cause were due to infectious agents, which was often atypical bacteria, Streptococcus pneumoniae, and/or respiratory viruses.1Vichinsky E. Neumayr L. Earles A. Causes and outcomes of acute chest syndrome in sickle cell disease.N Engl J Med. 2000; 342: 1855-1866Crossref PubMed Scopus (955) Google Scholar Notably, this study was conducted before implementation of the first pneumococcal conjugate vaccines and prior to widespread use of qualitative polymerase chain reaction for atypical bacteria and virus detection, potentially limiting contemporary application. FOR RELATED ARTICLE, SEE PAGE 150 In early 2020 in response to the COVID-19 pandemic, a number of nonpharmacologic interventions (NPIs) were implemented around the world in an effort to mitigate SARS-CoV-2 transmission and reduce morbidity and mortality rates. In France, NPI measures that included stay-at-home orders, physical distancing, school closure, workplace measures, and masking led to reduced transmission of SARS-CoV-2. Notably, these same interventions also led to significant reduction in the spread of other respiratory pathogens such as respiratory syncytial virus,2Stein R.T. Zar H.J. RSV through the COVID-19 pandemic: burden, shifting epidemiology, and implications for the future.Pediatr Pulmonol. 2023; 58: 1631-1639Crossref Scopus (6) Google Scholar influenza,3Stamm P. Sagoschen I. Weise K. et al.Influenza and RSV incidence during COVID-19 pandemic-an observational study from in-hospital point-of-care testing.Med Microbiol Immunol. 2021; 210: 277-282Crossref Scopus (33) Google Scholar and S pneumoniae4Brueggemann A.B. Jansen van Rensburg M.J. Shaw D. et al.Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.Lancet Digit Health. 2021; 3 (e360–e370)Google Scholar followed by a surge in transmission when these NPIs were lifted. The impact of NPI-associated changes in respiratory infections on ACS incidence among children with SCD has not been studied previously. In this issue of CHEST, Assad et al5Assad Z. Valtuille Z. Rybak A. et al.Unique changes in the incidence of acute chest syndrome in children with sickle cell disease unravel the role of respiratory pathogens: a time series analysis.Chest. 2024; 165: 150-160Abstract Full Text Full Text PDF Scopus (2) Google Scholar performed an interrupted time-series analysis of national hospital-based surveillance data in France to compare the incidence of hospitalizations for ACS during prepandemic (January 2015 to March 2020), NPI-implementation (April 2020 to March 2021), and NPI-lifting periods (April 2021 to May 2022). There was a significant decrease in ACS incidence after NPI implementation (-29.5%; 95% CI, ˗46.8% to ˗12.2%; P = .001) followed by an increase in hospitalizations for ACS after NPIs were lifted (+24.5%; 95% CI, 7.2%-41.6%; P = .007). A similar pattern was noted for hospitalizations for acute pain episodes in children with SCD (initial decrease of 33.7% [P < .001] during NPI implementation followed by an increase of 11% [P = .01] after NPI lifting), which is an important finding given the frequency of hospitalizations for pain (n = 52,254) compared with those for ACS (n = 2,306) during the study period overall. The investigators also sought to estimate the fraction of ACS cases attributable to specific respiratory pathogens. This was accomplished by correlating ACS incidence in children with SCD to the estimated circulation of selected respiratory pathogens among the general population of hospitalized children. They used monthly incidence of 12 respiratory pathogens from all hospitalized children in multivariable quasi-Poisson regression modelling. Results showed the fraction of ACS potentially attributable to S pneumoniae and influenza to be 30.9% and 6.8%, respectively, and that S pneumoniae incidence correlated with respiratory syncytial virus and influenza incidence. The fraction of ACS episodes potentially attributable to atypical bacteria (Mycoplasma pneumoniae and Chlamydia pneumonia) was not significant. This study demonstrated a profound impact of NPI measures on the incidence of ACS episodes during the COVID-19 pandemic, similar to what has been reported in acute pediatric illnesses such as asthma exacerbations and bronchiolitis.6Chiapinotto S. Sarria E.E. Mocelin H.T. Lima J.A.B. Mattiello R. Fischer G.B. Impact of non-pharmacological initiatives for COVID-19 on hospital admissions due to pediatric acute respiratory illnesses.Paediatr Respir Rev. 2021; 39: 3-8PubMed Google Scholar This is an important yet not surprising result, given that ACS episodes in children are often associated with an infectious trigger. An important finding from this study is that the change in incidence of acute severe pain episodes in children was similar to that of hospitalizations for ACS. Similar results have been reported by investigators from a single US hospital system, such that ED visits and hospitalizations for acute SCD pain decreased in 2020 compared with 2018 and 2019, followed by increases in 2021.7Romanos-Sirakis E. Demissie S. Emergency department visits and hospitalizations for pediatric vaso-occlusive pain events during the COVID-19 pandemic.Pediatr Blood Cancer. 2023; 70e30213Crossref Scopus (1) Google Scholar Although acute SCD pain can be triggered by multiple factors that include stress, cold temperatures, and dehydration, some studies have found associations between antecedent respiratory symptoms and acute SCD pain.8Diep R.T. Busani S. Simon J. Punzalan A. Skloot G.S. Glassberg J.A. Cough and wheeze events are temporally associated with increased pain in individuals with sickle cell disease without asthma.Br J Haematol. 2015; 170: 732-734Crossref Scopus (10) Google Scholar How and why NPI measures altered the natural history of hospitalizations for acute severe pain episodes in this large population-based study of children with SCD warrants additional study. The authors concluded that up to 30% of cases of ACS may be attributable to S pneumoniae; however, they did not find a significant contribution of atypical respiratory pathogens. This is in contrast to studies by the Acute Chest Syndrome Study Group in which M pneumonia and C pneumonia were common causes of ACS.1Vichinsky E. Neumayr L. Earles A. Causes and outcomes of acute chest syndrome in sickle cell disease.N Engl J Med. 2000; 342: 1855-1866Crossref PubMed Scopus (955) Google Scholar,9Dean D. Neumayr L. Kelly D.M. et al.Chlamydia pneumoniae and acute chest syndrome in patients with sickle cell disease.J Pediatr Hematol Oncol. 2003; 25: 46-55Crossref Scopus (45) Google Scholar,10Neumayr L. Lennette E. Kelly D. et al.Mycoplasma disease and acute chest syndrome in sickle cell disease.Pediatrics. 2003; 112: 87-95Crossref Scopus (60) Google Scholar Assad et al5Assad Z. Valtuille Z. Rybak A. et al.Unique changes in the incidence of acute chest syndrome in children with sickle cell disease unravel the role of respiratory pathogens: a time series analysis.Chest. 2024; 165: 150-160Abstract Full Text Full Text PDF Scopus (2) Google Scholar note the methods used may be less sensitive to identification of the role of atypical organisms in ACS pathogenesis. Given that "attributable fraction" results in the current study are extrapolated from population level data about prevalence of respiratory pathogens and are not based on diagnostic samples from patients with SCD and ACS, antimicrobial therapy practices should not be altered based on the results of this study. Current management of ACS includes the use of both a macrolide and third-generation cephalosporin for coverage of both atypical organisms and S pneumonia.11Howard J. Hart N. Roberts-Harewood M. Cummins M. Awogbade M. Davis B. Guideline on the management of acute chest syndrome in sickle cell disease.Br J Haematol. 2015; 169: 492-505Crossref PubMed Scopus (113) Google Scholar However, the importance of pneumococcal and influenza vaccinations should be emphasized. An important limitation of the current study was the exclusion of pneumonia from the case definition of ACS. Both clinically and for research purposes, ACS (defined as a new radiographic pulmonary infiltrate in the context of an acute respiratory illness) is clinically indistinguishable from pneumonia. A diagnosis of ACS provides no information about the underlying cause; a similar clinical syndrome may be due to many different causes. Attributing 30% of cases of this acute respiratory illness to S pneumonia while at the same time excluding pneumonia from the case definition appears to lack a clear clinical rationale. The results of a sensitivity analysis with the two diagnoses combined were consistent with the results for the primary ACS outcome that excluded pneumonia. The reason for separating the two diagnoses for the primary analysis remains unclear. The negative impact of NPIs for pediatric patients who live with SCD was not addressed in this study. Studies in adult patients with SCD have demonstrated the negative impact of NPI implementation, which includes isolation, psychological distress, delays in care, and decreased access to care.12Berghs M.J. Horne F. Yates S. et al.Black sickle cell patients' lives matter: healthcare, long-term shielding and psychological distress during a racialised pandemic in England: a mixed-methods study.BMJ Open. 2022; 12e057141Crossref Scopus (1) Google Scholar, 13Curtis S. Henny B. Joanna S. et al.Excess deaths among adults with sickle cell disease in 2020 compared to prior years.Ann Hematol. 2023; 102: 41-44Crossref Scopus (3) Google Scholar, 14Buscetta A.J. Abdallah K.E. Floyd K.J. et al.Examining resilience of individuals living with sickle cell disease in the COVID-19 pandemic.BMC Psychol. 2022; 10: 156Crossref Scopus (4) Google Scholar Because of the distinct confluence of enduring a chronic illness and belonging to a historically marginalized demographic amidst a period of global turbulence, it is imperative to consider the adverse ramifications of NPIs for pediatric patients with SCD. ACS is an important, common, and potentially life-threatening complication of SCD. Further understanding of the pathogenesis and potential triggers is imperative to advance care for children with SCD. The current study is among the first to associate NPI restrictions with changes in incidence of hospitalizations for ACS. These results warrant additional attention to understand what other factors, in addition to respiratory pathogen exposure, may have contributed to this change. The study also suggests that S pneumoniae and influenza infections play a significant role in pediatric ACS. A contemporary, large-scale prospective study is needed to understand the role of respiratory pathogens in the development of pediatric ACS in the postpneumococcal vaccine era. None declared. Unique Changes in the Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Unravel the Role of Respiratory Pathogens: A Time Series AnalysisCHESTVol. 165Issue 1PreviewNPIs were associated with significant changes in ACS incidence concomitantly with major changes in the circulation of several respiratory pathogens in the general population. This unique epidemiologic situation allowed determination of the contribution of these respiratory pathogens, in particular S pneumoniae and influenza, to the burden of childhood ACS, highlighting the potential benefit of vaccine prevention in this vulnerable population. Full-Text PDF

Background: The discriminatory and racist policy of historical redlining in the United States during the 1930s played a role in perpetuating contemporary environmental health disparities. Objective: Our objectives were to determine associations between home and school pollutant exposure (fine particulate matter [PM2.5], NO2) and respiratory outcomes (Composite Asthma Severity Index, lung function) among school-aged children with asthma and examine whether associations differed between children who resided and/or attended school in historically redlined compared to non-redlined neighborhoods. Methods: Children ages 6 to 17 with moderate-to-severe asthma (N = 240) from 9 US cities were included. Combined home and school exposure to PM2.5 and NO2 was calculated based on geospatially assessed monthly averaged outdoor pollutant concentrations. Repeated measures of Composite Asthma Severity Index and lung function were collected. Results: Overall, 37.5% of children resided and/or attended schools in historically redlined neighborhoods. Children in historically redlined neighborhoods had greater exposure to NO2 (median: 15.4 vs 12.1 parts per billion) and closer distance to a highway (median: 0.86 vs 1.23 km), compared to those in non-redlined neighborhoods (P < .01). Overall, PM2.5 was not associated with asthma severity or lung function. However, among children in redlined neighborhoods, higher PM2.5 was associated with worse asthma severity (P < .005). No association was observed between pollutants and lung function or asthma severity among children in non-redlined neighborhoods (P > .005). Conclusions: Our findings highlight the significance of historical redlining and current environmental health disparities among school-aged children with asthma, specifically, the environmental injustice of PM2.5 exposure and its associations with respiratory health.

Background: Acute chest syndrome (ACS), the second most common cause of hospitalization and leading cause of death in children with sickle cell disease (SCD), often develops during a hospitalization for acute SCD in the setting of chest wall splinting, hypoventilation, and atelectasis from pain and opioid use. While incentive spirometry is an important component of ACS prevention and management, additional strategies are needed to prevent atelectasis during sleep. Bi-level positive airway pressure ventilation (BiPAP) provides positive pressure breaths through a mask to support ventilation, and is most commonly used to treat respiratory failure and chronic obstructive sleep apnea,. In 2021, we published our clinical innovation using BiPAP during sleep as supportive care during 53 hospitalizations on the general pediatric inpatient unit for hospitalized children with SCD to prevent ACS and/or to prevent acute respiratory failure among children with mild-moderate ACS. We found that our novel use of BiPAP was safe and feasible on a general pediatric unit; when recommended, it was tolerated in 40/53 (75%) hospitalizations. The goal of the current qualitative study was to identify perceived benefits and harms, and facilitators and barriers to the use and widespread implementation of “supportive non-invasive ventilation for ACS prevention” (SNAP) on a general pediatric inpatient unit. Methods: We conducted semi-structured interviews with key implementation partners at Boston Medical Center (pediatric hospitalists and hematologists; nurses, respiratory therapists, child life specialists, clinical leadership, patients, and parents) about their experiences with and perceptions of SNAP. Interviews and a priori codes for the preliminary codebook were guided by the Promoting Action Research on Implementation in Health Services (PARiHS) framework using the Evidence, Context, and Facilitation constructs. Interviews were transcribed, checked for accuracy, and imported into NVivo 12 for analysis. Transcripts were double coded by three team members who independently coded the initial transcripts. The codebook was refined until consensus was reached. Team members independently reviewed data to identify preliminary themes and subsequently consolidated themes as a group. We were particularly interested in themes regarding benefits, advantages, disadvantages, facilitators, and barriers to individual use and institutional implementation of BiPAP as supportive care. Results: Interviews were completed with 16 participants until thematic saturation was reached, including: 5 physicians, 4 nurses, 1 respiratory therapist, 1 child life specialist, 3 parents, and 2 patients. One physician and one nurse had administrative leadership roles. Major themes included: 1) Participants believed that BiPAP is effective at preventing ACS and - when already present - effective at preventing ACS from getting worse. 2) Despite some initial hesitation, inpatient team members endorsed that use of BiPAP on the general pediatric inpatient unit is appropriate. 3) Improving the patient experience with BiPAP is essential and requires a multi-tiered approach including both physical and social components. 4) Communication among inpatient team members and between staff and patients was critical for BiPAP initiation and success. 5) Nurses were key to the intervention success and required additional support. 6) The size of clinical unit and a “buy-in” culture supported intervention success . See Table 1 for detailed subthemes. Conclusions/Future directions: Members of the health care team, patients, and parents perceive SNAP as effective at preventing ACS and respiratory decompensation, and believe that it is appropriate for use with stable hospitalized children at risk for ACS on a general pediatrics inpatient unit. Features of our inpatient pediatrics unit (small size and collaborative relationships between physicians, staff, and nursing leadership) facilitated successful implementation. Improving the patient experience remains a challenge, and will involve technical issues (mask comfort and pressure) and enhanced communication among health care team members and between staff, patients, and caregivers. We are utilizing these data to develop a protocol for a multicenter hybrid effectiveness/implementation trial of SNAP that incorporates these strategies.