Introduction. CCHS is a rare disorder caused by PHOX2B gene variants. While CCHS hallmarks are hypoventilation and respiratory control dysfunction necessitating lifelong artificial ventilatory support, affected individuals also experience widespread, but less studied, autonomic nervous system (ANS) dysregulation. PHOX2B variants may be divided into moderate and severe groups based upon molecular and in-silico data. The International CCHS Registry is a secure repository for longitudinal data from individuals with a PHOX2B variant-confirmed diagnosis, including information on seven systems served by the ANS (cardiovascular, gastrointestinal, neurological, ophthalmologic, renal/urinary, respiratory, sudomotor). Our objective was to analyze patient-reported symptoms (PRS) across all ANS-served systems and determine their relationship with PHOX2B variant severity. We hypothesized an increase in PRS in all organ systems in individuals with severe variants. Methods. This study focused on completed initial surveys. Descriptive statistics were generated for all PRS, and by variant groups, with statistical comparison using the Wilcoxon Rank-Sum and Fisher’s exact tests. Results. Analysis of 148 surveys confirmed broad, multi-system ANS dysfunction in CCHS. Those with severe PHOX2B variants were more likely to report cardiovascular, gastrointestinal, neurological, and ophthalmological system dysfunction compared to individuals with moderate variants. Individuals with severe PHOX2B variants reported significantly more symptoms in 6/7 organ systems than those with moderate variants. Conclusions. The individual-reported impact of CCHS varies by both PHOX2B variant severity and the ANS organ system/symptom manifestations. Beyond the traditional clinical focus on cardiorespiratory dysfunction, these results highlight other ANS-related systems that are critical for comprehensive clinical management and future therapeutic trial design.

Background Bronchopulmonary dysplasia (BPD) is a heterogeneous syndrome encompassing multiple biological and structural phenotypes. This study aimed to identify latent phenotypic subgroups of preterm infants with BPD and characterize their clinical and perinatal profiles. Methods We conducted a retrospective cohort of preterm infants born at ≤32 weeks’ gestation and admitted to a tertiary neonatal unit in Medellín, Colombia (2021–2023). Infants with major malformations or genetic syndromes were excluded. Clinical and respiratory variables were analyzed using latent class analysis (LCA) to identify subgroups based on markers of prematurity, oxygen dependency, and respiratory support. Results Among 236 infants, a three-class model best described the data (AIC = 12,002; BIC = 12,440; entropy = 0.83). Class 1 (64%) comprised more mature infants with mild respiratory disease and 5% mortality. Class 2 (27%) showed prolonged oxygen therapy and intermediate outcomes. Class 3 (9%), composed mainly of extremely preterm infants, exhibited severe respiratory failure and 88% mortality. The classes reflected a progression from mild inflammatory to interstitial and vascular phenotypes. Conclusions LCA revealed three distinct BPD phenotypes with increasing respiratory severity and mortality, paralleling biological models of parenchymal, interstitial, and vascular injury. This approach supports data-driven phenotyping as a foundation for precision neonatal care.

Clinical correspondence

Objectives: Nirsevimab was approved in Europe in 2022 for respiratory syncytial virus (RSV) prevention. In October 2023 Catalonia, a region of Spain, launched a universal immunization program for infants under 6 months during their first RSV season. The aims are assessing the characteristics of patients admitted with bronchiolitis following nirsevimab’s implementation and comparing the features of the immunized patients during two seasons. Methods: This prospective, observational, single-center study included patients aged up to 12 months old admitted for bronchiolitis between October 2023 and May 2025, comparing clinical and epidemiological data across two seasons (S1: October 2023-May 2024; S2: October 2024-May 2025). Results: 574 patients were included (S1: 352; S2: 222), with a median age of 3.2 months (interquartile range [IQR]:1.5-6.5). Most were previously healthy (437/574, 76.1%) and immunized (406/574, 70.7%). RSV was detected in 215/574 (37.5%) of cases. 159/574 (27.7%) required ICU admission, and the median length of hospital stay was 5 days (IQR:3-8). In S2, immunization rates increased (S1:61.6% vs S2:85.1%, p-value=<0.001) and RSV infections decreased (S1:41.2% vs S2: 31.5%, p-value=0.020). Among immunized patients, S2 showed a higher proportion of healthy children (S1:65.0% vs S2:77.8%,p-value=0.005), fewer ICU admissions (S1:33.2% vs S2:21.2%,p-value=0.007) and shorter hospital stays (S1: 6 [IQR:4-9.5] days vs S2: 5 [IQR:3-7.5],p-value=0.033). Conclusion : Following nirsevimab implementation, immunized patients in the second season had milder outcomes, including fewer ICU admissions and shorter hospital stays.

As survival improves for individuals with cystic fibrosis (CF) worldwide, the number of adolescents requiring transition from pediatric to adult care is rapidly growing. In addition to limited resources, lack of uniform access to medical care, access to traditional and advanced therapies, the increasing number of transitioning young adults in low- and middle-income countries (LMICs) face barriers and challenges to safe transition from pediatric to adult healthcare that are both universal and unique. This shift in demographics presents distinct challenges due to underdeveloped and under-resourced adult CF care infrastructure, sociopolitical variation, and cultural complexities. This manuscript focuses on healthcare transition (HCT) of people with CF (pwCF) in LMICs, identifies key barriers, and explores cultural, religious, and health system factors. Additionally, we emphasize the practical need to transition adolescents to adult care to maintain pediatric hospital capacity for younger children, as well as the developmental and educational needs of young adults entering a medical system that is challenging for adults without chronic disease. With much of the transition literature reflecting health systems in high-income countries (HIC), this integrated socio-ecological and socio-cultural overview underscores the urgent need for context-specific, culturally sensitive transition frameworks focused on reproductive and mental health, the integration of adolescent-responsive, family-inclusive, and even faith-informed care models in LMICs.

Background: Bronchiolitis represents a major cause of infant hospitalization, predominantly due to respiratory syncytial virus (RSV). Nirsevimab, a long-acting monoclonal antibody targeting the prefusion RSV F protein, has recently been introduced to provide season-long protection against RSV-related lower respiratory tract infection. Methods: We conducted a multicenter, retrospective, population-based study across the Liguria Region (Northwest Italy) to assess the impact and effectiveness of the 2024–2025 nirsevimab immunization campaign. All infants under two years of age hospitalized with acute bronchiolitis between October 2023 and March 2025 were identified through the regional pediatric Hub-and-Spoke network. Data were compared between the pre-nirsevimab (2023–2024) and post-nirsevimab (2024–2025) seasons. Nirsevimab effectiveness (VE) against RSV-positive hospitalization was estimated using a test-negative design. Results: A total of 858 infants were hospitalized with bronchiolitis across the two seasons. Following the introduction of nirsevimab, bronchiolitis hospitalizations decreased from 41.7 to 17.3 per 1000 admissions (Incidence Rate Ratio 0.4; 95% CI: 0.4–0.5; p<0.001), corresponding to a 60% reduction. Estimated nirsevimab effectiveness was 65.0% (95% CI: 39.2–79.8%) against RSV-positive hospitalization. No high-risk infants—those previously eligible for palivizumab—developed severe RSV infection requiring PICU admission. Breakthrough infections occurred in a minority of immunized infants but showed a similar clinical course to non-immunized cases. Conclusions: The introduction of universal nirsevimab immunization in Liguria was associated with a marked reduction in RSV-related hospitalizations, confirming its strong real-world epidemiological impact. These findings support nirsevimab as an effective and feasible public health intervention to substantially reduce the burden of RSV bronchiolitis in infants.

10/21/2025Editorial OfficePediatric Pulmonologyvia Submission portal

TitleViral infection-associated plastic bronchitis demonstrating eosinophil extracellular trap formation: a case report

Background: Approximately 1,500 children in Canada are diagnosed with cystic fibrosis (CF) 1. A childhood CF diagnosis has substantial implications for the mental health of parent caregivers (referred to as parents herein), who report elevated levels of emotional distress, stress, depression, and anxiety 2. Tailored, psychosocial resources for this population are scarce and barriers exist to accessing community mental health services 3. Internet-delivered programs present a promising mode of mental health resource delivery for this specialized population, but none are available in Canada. To inform the development of such a resource, the present study examined the lived experiences and information and resource needs of parents of children with CF. There were no established hypotheses due to the exploratory nature of the study. Methods: Twenty-three parents ( M age = 45.65, SD = 8.91) in Canada participated in the study. Each participant completed a consent form, demographic questionnaires, and a semi-structured interview. All interviews were audio-recorded, transcribed verbatim, and analyzed using reflexive thematic analysis. Results: Six major themes were generated: (1) challenges, (2) needs, (3) emotions and coping, (4) healthcare experiences, (5) unique parenting experiences, and (6) Internet-delivered resource considerations. Subthemes were also generated for each major theme. Conclusions: These findings highlight the unique lived experiences and needs of parents of children with CF. The results indicate that parents would value an Internet-delivered resource that provides tailored information about several topics. The information gained from this study will be utilized to develop an accessible, tailored, Internet-delivered resource for parents of children with CF.

Introduction: Percutaneous Endoscopic Gastrostomies (PEG) are used to support nutritional adequacy, growth and lung function in people with Cystic Fibrosis (CF). Adults with CF living with a PEG face unique challenges due to the time and length of placement often being inserted in childhood and extending through to adulthood. In the era of CF modulator therapies removal of PEG is increasingly being contemplated, and our aim was to understand experiences and perspectives of adults with CF living with a PEG. Methods: This was a single-centre qualitative study in adults with CF living with a PEG. All semi-structured interviews were audio recorded, transcribed and analysed inductively using grounded theory methodology. Data saturation was reached when no new codes emerged. Findings were summarised into major conceptual themes. Participant demographics and medical history were obtained. Results: In total, thirteen participants completed semi-structured interviews. Analyses revealed four main themes in adults with CF living with a PEG: (1) Psychological (i.e. body image, embarrassment, isolating/ social stigma, acceptance/adjustment), (2) Pain & physical concerns (i.e. general pain, hyper granulation, leaking), (3) Social (i.e. relationships and navigating social conversations), and (4) Functionality. Conclusion: Our study explored lived experiences of adults with CF living with a PEG. We found there was significant psychological and social impact of growing up with a PEG, highlighting the need for clinicians to provide holistic support that addresses both physical and mental challenges of long-term gastrostomy care for adults with CF.

A document by Avram Rago. Click on the document to view its contents.

Objective: Social drivers of health (SDOH) impact health outcomes for children with asthma. Advances in geocoding have enabled better SDOH measurement in research. We aimed to: 1) examine relationship between three SDOH composite indices – Social Vulnerability Index (SVI), Childhood Opportunity Index 3.0 (COI), Area Deprivation Index (ADI) – and asthma patient disposition from the emergency room; and 2) determine which index most closely correlates with admission rates. Methods: Retrospective cohort study of patients 2-18 years presenting with asthma, defined using a computational phenotype requiring: asthma diagnostic code, ≥2 doses of nebulized albuterol, and ≥1 systemic steroid dose within 24 hours of presentation. Data were obtained from 2021-2024 from the Indiana Network for Patient Care, a state-wide health information exchange. Exposures included the three SDOH indices. We used multinomial logistic regression to evaluate associations with patient disposition and recurrent emergency room encounters. Results: Total of 5,965 asthma encounters (4,539 patients) were included, 29.5% of which resulted in admission (56.6% ward, 43.4% ICU). Female gender, chronic illness, ‘other’ preferred language, and >1 year since last outpatient visit increased likelihood of admission. Black race and preferred language of Spanish were associated with lower likelihood (vs. white, English-speaking reference). SVI was the index most closely linked to asthma outcomes and remained in the final regression model, though not statistically significant. Conclusions: Race, language, health insurance, and preventive healthcare access are key drivers of emergency and repeat hospital use in pediatric asthma. SVI may be the most effective ‘geomarker’ to identify high-risk areas for targeted action.

Introduction: Cystic fibrosis (CF) is a severe genetic disorder caused by pathogenic variants in the Cystic Fibrosis Transmembrane Conductance Regulator ( CFTR) gene, leading to multisystem complications including chronic rhinosinusitis and nasal polyposis. Recent advances in CFTR modulator therapies have revolutionized systemic disease control, but their impact on sinonasal disease remains less explored. Methods: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42025632498). Searches were performed across PubMed/MEDLINE, Cochrane Library, and Embase through March 2025. Studies reporting nasal endoscopic outcomes using validated scoring systems before and after CFTR modulator therapy were included. Results: Out of 232 identified records, 10 studies met inclusion criteria, representing populations from six countries. Most studies assessed triple therapy (Elexacaftor/Tezacaftor/Ivacaftor). Endoscopic scores, including the Modified Lund-Kennedy scale, showed significant reductions in nasal polyps, mucosal edema, and discharge. Pediatric and adult groups benefited alike, with triple therapy proving more effective than dual or monotherapy. Secondary outcomes included improved pulmonary function, weight gain, and olfactory recovery. Conclusion: This review demonstrates that CFTR modulators provide significant benefits for sinonasal disease in CF, reinforcing their role as a comprehensive therapeutic approach addressing both upper airway and systemic disease burdens.

Cystic fibrosis (CF) presents significant challenges for both patients and their families. However, the mental health needs of persons with cystic fibrosis (PWCF) in low- and middle-income countries (LMICs) remain underexplored. Limited resources, fragmented healthcare systems, and inequities in access to essential CF treatments often compound psychological stressors such as depression, anxiety, and caregiver burden. This review examines existing literature on the mental health and psychosocial challenges of PWCF and their families in LMICs, highlighting the intersection between inadequate physical healthcare and poor mental health outcomes. Findings suggest that disparities in access to diagnostic services, medications, and multidisciplinary care exacerbate emotional distress, leading to poorer quality of life compared to counterparts in high-income countries. Families often experience financial strain, social isolation, and limited psychosocial support, which further magnify mental health challenges. Addressing these inequities requires integrating mental health care into routine CF management, even in resource-limited settings. Low-cost strategies such as regular mental health screening, translating available CF-specific mental health resources, and the provision of brief interventions via digital and internet-based technologies show promise for sustainable implementation. The review underscores the need for increased research in LMIC contexts and the development of scalable interventions that address both physical and psychological dimensions of CF. Ensuring parity with high-income countries demands recognition of mental health as a core component of CF care.

Introduction: Cystic fibrosis (CF) is an autosomal recessive disease resulting from mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene. Recurrent respiratory infections are a common problem, and patients receive frequent antibiotics. Treatment of CF involves both symptomatic and underlying disease-targeting therapies. Elexacaftor/tezacaftor/ivacaftor (ETI), a disease-targeting therapy, combines two correctors and a potentiator to increase functioning of the CFTR channel. With better functioning channels, symptomatic improvement is expected in the form of decreased respiratory infections. Objective: To evaluate the change in antibiotic use following the initiation of ETI therapy in pediatric patients. Methods: This is a single-center, retrospective chart review conducted at Nationwide Children’s Hospital (NCH) in Columbus, Ohio. Patients served as self-controls, compared before and after initiating ETI. The primary outcome was change in antibiotic days per patient-year. Secondary outcomes included change in specific antibiotic use, enteral versus intravenous therapy, and different classes of antibiotics. The study was approved by the NCH IRB. Results: 139 patients were included. The median antibiotic days per patient-year was 17 days pre-ETI and 6 days post-ETI (p<0.001). There was a significant decrease in antibiotic days per patient-year for intravenous antibiotics, enteral antibiotics, intravenous vancomycin, linezolid/tedizolid, anti-methicillin-resistant Staphylococcus aureus (MRSA) tetracyclines, other anti-MRSA medications (clindamycin and sulfamethoxazole-trimethoprim), aminoglycosides, anti- Pseudomonas aeruginosa (PSAE) beta-lactams, and fluoroquinolones. There was no significant difference in carbapenems or non-anti-PSAE beta-lactams. Conclusion: ETI therapy was associated with decreased antibiotic days for many therapeutic classes of both enteral and intravenous antibiotics.

Humans nasal and bronchial epithelium in CF: Differences in protein expression

Introduction: Bronchiectasis in children is a neglected chronic suppurative lung disease that imposes a substantial burden on children and adolescents and their families, adversely affecting quality of life (QoL). 1 Incorporating health-related quality of life (HRQoL) tools into routine care can improve outcomes by highlighting disease burden and guiding tailored interventions. This scoping review aimed to identify self-reported questionnaires assessing QoL in pediatric bronchiectasis (PB). Methods: Following the PRISMA extension for scoping reviews, we searched Embase, CINAHL, MEDLINE, Cochrane Central Register of Controlled Trials, PsycINFO, and PubMed for articles published in English since 2000. Pre-specified keywords (QoL, children, adolescents, bronchiectasis, lung disease, patient reported outcome measures (PROM), primary ciliary dyskinesia, cystic fibrosis) and related index terms were used. Studies employing questionnaires or items assessing QoL in children and adolescents with bronchiectasis were included without geographical restrictions. Two authors independently screened and appraised eligible manuscripts. Results: The search yielded 731 articles, of which 373 were relevant to respiratory diseases. Thirty-three met inclusion criteria, identifying 15 unique HRQoL tools used in bronchiectasis or related conditions. Only five (33%) of these tools were developed for adults with bronchiectasis and no pediatric-specific bronchiectasis HRQoL questionnaires were identified. Conclusion: This scoping review highlights the absence of any validated, pediatric-specific HRQoL tools for bronchiectasis. Developing such a questionnaire, informed by existing instruments and our review findings, is an urgent priority. A validated tool will enhance understanding of disease impact on children, adolescents and their families, supporting tailored clinical care and research interventions.

Atypical presentation of Neuroendocrine cell Hyperplasia of Infancy (NEHI)Authors: Ashish George, Mark Minor, Amanda Gutwein, Mutaz Alsanjalawi, Elizabeth Bacon, Daniel EvansAffiliation: Dayton Children’s Hospital, Dayton, OHKeywords: NEHI, chILD, High-flow, Case report