Image correspondence- Iatrogenic diaphragmatic hernia mimicking pneumonia-

“Post-COVID bronchiolitis severity: more of an attitude shift than a true change”

Background: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder characterized by autonomic dysregulation and abnormal control of breathing, necessitating lifelong artificial ventilation. The impact of CCHS on patient quality of life (QoL) and caregiver burden remains unquantified. Methods: A cross-sectional study of QoL in CCHS patients (≥12 years; WHOQOL–BREF) and burden in CCHS caregivers (Zarit Burden Interview) was conducted. Participants were recruited from CCHS support organizations. Participant age group, sex, primary language, and country of residence were collected. Results: 271 individuals (78 CCHS, 193 caregivers) from 15 countries participated. CCHS patients reported significantly reduced physical, psychological, and social relationships domain scores compared to healthy controls (p<0.01), yet >70% reported good overall QoL. Over half reported moderate or worse impact on QoL items including medical treatment dependence and cognitive function. Young CCHS patients (<25 years) reported better overall QoL and general health than those ≥25 years. CCHS caregiver burden was increased compared to that reported in other chronic diseases, with >50% reporting frequent caregiving-induced stress. Caregivers who reported financial issues also reported higher total burden (p<0.05). Conclusions: CCHS QoL scores are depressed compared to healthy individuals. This study identified specific domains of QoL and caregiver burden most impacted by CCHS, revealed a relationship between age and QoL in CCHS, and finances and burden in caregivers. Results offer targets for future interventions to enhance QoL in CCHS and reduce caregiver burden. Further work is needed to elucidate the relationship between CCHS impact and disease- and treatment-specific factors.

Rationale: Extremely preterm infants are at highest risk for developing bronchopulmonary dysplasia (BPD). This study aimed to examine the relationship between gestational age and respiratory outcomes in children with BPD in the outpatient setting. Methods: Data were collected from 1,025 preterm children with BPD recruited from outpatient bronchopulmonary (BPD) clinics at Johns Hopkins and Children’s Hospital of Philadelphia (CHOP). Extremely preterm children (22-24 and 25-27 weeks gestation) were compared to a reference group of very preterm children (28 to 32 weeks gestation). Data were analyzed using Chi-square tests, t-tests, and ANOVA tests. Results: Infants born at <25 weeks gestation were more likely to have severe BPD (71.9%), be discharged on supplemental oxygen (50.7%), have public insurance, and self-report as Black (60.4%) compared to those born >25 weeks. In the outpatient setting, extremely preterm children (22-24 weeks gestation) had a higher likelihood of activity limitation (OR 1.72) compared to very preterm infants. Hispanic children, regardless of gestational age, were more likely to have sick visits (OR 2.09) and a hospital admission (OR 2.15) compared to non-Hispanic children. Children with public insurance had a higher likelihood of ED visits (OR 1.48), hospital admissions (OR 1.49), systemic steroid use (OR 1.39), nighttime respiratory symptoms (OR 1.66), and activity limitations (OR 1.61) compared to privately insured children. Conclusions: After initial hospital discharge, extremely preterm children (22-24 weeks gestation) have a higher likelihood of activity limitation. However, other factors including race/ethnicity and public insurance are more likely driving outpatient respiratory outcomes regardless of gestational age.

First Case of Primary Ciliary Dyskinesia in GreenlandAuthors: Caroline Nygaard1 MD, Morten Dunø2 Ph.D., Carsten Johan Heilmann3MD, June K. Marthin1 Ph.D., Sarah Nygaard1 BM, Tavs Qvist4 Ph.D., Hanne Lynge Rex3 MD, Kim G. Nielsen1,5 MD, Dr. Med. Sci.Affiliations: 1Danish PCD Centre, Danish Pediatric Pulmonary Service, Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 2Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Denmark.3Medical Department M, Queen Ingrid’s Hospital, Nuuk, Greenland. 4Danish PCD Centre, Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark. 5Institute of Clinical Medicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, DenmarkEmails: [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected] author: Caroline Nygaard, Adress: Department of Pediatrics and Adolescent Medicine, JMC, Rigshospitalet, Blegdamsvej 9, DK-2100 København Ø, Denmark, Telephone: +4552131414, Fax: +4535456717, E-mail: [email protected] of interest : No conflicts of interestEthical statement: The parents have given written informed consent to the use and presentation of patient data, including photos. Exemption from ethics approval: The Regional Health Research Ethics Committees in the Capital Region in Denmark waived the need for ethical approval of the project (no. F-24062931)Keywords: Primary cilia dyskinesia, Genetics, GreenlandRunning Head: Primary cilia dyskinesia in GreenlandClinical correspondence

Background: Cystic Fibrosis Foundation guidelines recommend human milk (HM) as the ideal source of nutrition for children with CF (cwCF). Despite known pulmonary and nutritional benefits, fewer cwCF ever receive HM compared to the general population. Early nutrition choices are preference-sensitive, yet little is known about the factors that impede or sustain HM feeding among parents of cwCF. Objectives: Explore perceptions and experiences of mothers of cwCF who initiated HM feeding. Methods: Mothers of cwCF aged ≤10 years completed audio-taped, semi-structured interviews describing their experiences with HM feeding. Interviews were transcribed and two researchers independently coded the transcripts and conducted content and thematic analysis using an inductive approach. Results: Participants included 28 mothers who initiated HM feeding. Major themes included 1) the impact of a CF diagnosis on HM feeding plans 2) CF-specific challenges to HM feeding 3) mixed perceptions of the CF team’s support for HM feeding and of the role of formula in CF nutritional care and 4) the benefit of lactation consultants as part of the CF care team. Conclusion: Many parents prioritize HM for their cwCF given the well-established health benefits. However, CF-specific barriers to HM feeding are common and nutritional challenges necessitating fortification add additional barriers to sustained HM feeding efforts. While HM may improve long-term pulmonary outcomes, our findings demonstrate the need for personalized support for mothers desiring to HM feed to facilitate shared decision-making around options to optimize early nutritional status among cwCF.

Background: People with cystic fibrosis (pwCF) often have multifactorial peripheral muscle abnormalities attributed to, for example, malnutrition, steroid use, altered redox balance and, potentially, CF-specific intrinsic alterations. Malnutrition in CF now includes an increasing prevalence of overweight and obesity, particularly in those treated with CF transmembrane conductance regulator (CFTR) modulators. We aimed to characterise peripheral muscle function and body composition of pwCF on Elexacaftor/Tezacaftor/Ivacaftor (ETI) CFTR modulator treatment, compared to healthy controls. Methods: Fifteen pwCF on ETI, and 15 healthy age- and sex-matched controls (CON), underwent whole-body dual-energy X-ray absorptiometry scans, and a comprehensive evaluation of peripheral muscle function. These tests included quadriceps maximal isometric force measurement, an intermittent isometric quadriceps fatiguing protocol, handgrip strength dynamometry, squat jump height assessment, and a 1-minute sit-to-stand test. Results: No differences in quadriceps maximal isometric force (CON: 181.60 ± 92.90 Nm vs. CF: 146.15 ± 52.48 Nm, P = 0.21, d = 0.47), handgrip strength (CON: 34 ± 15 kg vs. CF: 31 ± 11 kg, P = 0.62, d = 0.18), peripheral muscle endurance, fatigue, or power were observed between the groups ( P>0.05). Moreover, no differences in whole-body, trunk or limb lean mass, fat-free mass, fat mass, or whole-body bone mineral density were evident ( P>0.05). Conclusion: Comparable peripheral muscle mass and function may be achievable in pwCF on ETI, especially those with good lung function. Research is needed to confirm these improvements in pwCF who have more severe lung disease, are less physically active, and have less optimal nutrition and exercise support.

Assessment of phrenic nerve pacers in a patient with Congenital Central Hypoventilation SyndromeTo the Editor:A 13-year-old patient with Congenital Central Hypoventilation Syndrome (CCHS) was transported to the emergency department following an unwitnessed syncopal event with associated cyanosis. She opened her eyes within a few minutes, her mental status returned to normal, and her oxygen saturation increased back to above 95%. Her parents reported she’s had two or three similar events over the past few months. She was born at 38-week gestation with recurrent central apnea noted immediately after birth. Genetic tests revealed that she was heterozygous for a 36 base pair duplication from nucleotide 729 to 764 of the PHOX2B gene (c 729_764dup36), which encodes an additional 12 alanine residues in the polyalanine tract of the PHOX2B protein (p.Ala244_Ala255dup12). With confirmation of a diagnosis of CCHS1, a tracheotomy was performed, and she was discharged home on positive pressure ventilation. By the end of her first year of life, she was able to be weaned to just mechanical ventilation when sleepy or asleep. At 5 years of age, bilateral phrenic nerve pacers were implanted, and she was successfully decannulated and transitioned from positive to negative pressure ventilation (Avery Diaphragm Pacing System, Avery Biomedical Devices, Inc, Commack, NY. At 7 years of age, she was diagnosed with absence epilepsy and placed on levetiracetam with resolution of her seizures. At 8 years of age, prolonged sinus pauses of up to 6 seconds were documented by an implantable loop recorder, and a cardiac pacemaker was implanted.Vital signs and physical examination in the ED were unremarkable, and neuro, cardiology, and pulmonary consults were obtained. There were no signs of infection; chest x-ray and electroencephalogram were unremarkable. Her cardiac pacemaker was interrogated, and there was no evidence that her cardiac pacemaker had been activated before, during, or after her syncopal episode. A 12-lead electrocardiogram (EKG) was obtained (figure 1). This EKG suggests her phrenic nerve pacemakers are functioning normally, with a set rate of 17 breaths per minute. Approximately every 3.5 seconds, 27 electrical pulses over 1.32 seconds are noted, particularly well seen on leads II, III, aVR, aVL, aVF, and V3-V6. Iron deficiency was noted, and it was subsequently confirmed that she suffered from menorrhagia. Her syncopal episode was judged most likely vasovagal in origin, exacerbated by iron deficiency anemia. Realizing the noteworthy aspects of the case, informed consent was obtained from the patient and her family to publish this case report. This case report is exempt from IRB approval by the New York Medical College Institutional Review Board as per the policy in their manual, “If case reports are not identifiable, there is no need…to contact or to submit any documents to the IRB”.Following the seminal work of Glenn WL, et al 2, diaphragmatic pacing has been utilized in patients with spinal cord injuries or patients with amyotrophic lateral sclerosis3. Some patients with CCHS are being transitioned to ventilation with phrenic nerve pacers, thus permitting tracheostomy closure4.Syncope is not uncommon in patients with congenital central hypoventilation syndrome. Patients with CCHS are at risk for life-threatening cardiac arrhythmia and may sometimes require cardiac pacemakers. Patients being ventilated with phrenic nerve pacers without a tracheostomy, are also at risk for obstructive sleep apnea. Patients with CCHS are prone to fainting, and tilt-table testing confirms they are prone to greater orthostatic decreases in blood pressure than healthy control patients.The artefact due to phrenic nerve pacer discharge in figure 1 has been previously demonstrated in the literature. In 1987, Auerbach and Dobelle reported trans telephonic monitoring of patients with implanted neurostimulators, including a similar figure to ours, using 2 EKG leads5. A similar figure was published in a case report of a patient who developed ventricular tachycardia and cardiac arrest during diaphragmatic pacing, and on polysomnography in a patient with CCHS.In conclusion, a routine EKG may be an easy and quick way to determine if phrenic nerve pacers are functioning properly. Both the frequency and amplitude of phrenic nerve stimulation can be estimated on an EKG.

Background & aim: Children and young people (CYP) with severe, sub-optimally controlled asthma and co-existing allergic sensitisation to indoor aeroallergens, such as pet dander and house dust mite (HDM), would likely benefit from reduced allergen exposure. Multiple allergen remediation interventions exist and are often suggested to families in secondary care asthma clinics in the United Kingdom. Evidence suggests remediation uptake is low or partial but there is sparse evidence to explain why. This study aims to explain how families in this situation make decisions about home-based allergen remediations. Methods: In-depth qualitative interviews with CYP and mothers were analysed, and a grounded theory approach was used to develop a theory to explain decision-making processes and behaviours. Results: Ten CYP aged 11-15 years and 11 mothers were interviewed. The core finding was that families iteratively respond to changes in how certain they are in their asthma management decisions and actions. For allergen remediation uptake, this certainty varied depending on seeing an outcome-exposure relationship, understanding asthma severity, variability, and asthma control at the time of remediation decision-making. Understanding the mechanistic role of allergen exposures in asthma was challenging for families, and ongoing bi-directional communication with clinicians was essential in supporting long-term decision-making. Conclusion: The theory explains the often elongated, reactive process of allergen remediation decision making and implementation. It also explains other elements of family management of asthma, and their interconnections. Families’ iterative responsiveness suggests opportunities to intervene and promote earlier, preventative behaviour change.

Asthma is a significant public health concern, particularly in low- and middle-income countries (LMICs), which are predominantly located in regions such as North Africa, sub-Saharan Africa, South, Central, and East Asia, the Middle East, Latin America, the Caribbean, and certain parts of Europe. According to the World Health Organization (WHO), nearly 300 million individuals globally suffer from asthma. Data from the GAN Phase I study indicates that approximately one in ten children are asthmatic, with one in twenty experiencing severe asthma. Moreover, in children, 40% in LMICs have poor asthma control, compared to 19.9% in HICs.(1) It is estimated that 90% of the global burden of asthma is borne by individuals in LMICs, where death rates due to asthma are also the highest.(2) Also, in LMICs, children make up a larger proportion of the population compared to higher-income nations, which results in a correspondingly greater burden for those countries on health services due to childhood diseases. Estimates suggest that high proportion of asthma patients reside in LMICs, its prevalence over the past two decades is only increasing or remaining high, and morbidity-mortality rates associated with the condition are disproportionately higher compared to its counterpart high-income countries (HICs). (3)

Indoor air pollution represents a major health problem in developing countries. Common sources of household contaminants in these settings include gas or wood-fired stoves and ovens, heaters, fireplaces, tobacco smoke, dust mites, pets, mold, insecticides, and cleaning products. The use of biomass fuels or coal for daily activities, such as cooking, heating and lighting, are still common practices among many Latin American countries because of cultural behaviors, geographical conditions and limited access to cleaner energy sources. Inefficient combustion of these substances results in the release of toxic products, mainly nitrogen dioxide (NO2), carbon monoxide (CO), particulate matter (PM) and volatile organic compounds (VOC). Additionally, tobacco consumption is frequent in the region and is a well-known cause of air pollution, while electronic cigarettes have also gained popularity worldwide and are now a new source of airborne chemicals. Exposure to all these substances has been associated with an increased risk of health issues, particularly in children, such as growth impairment, respiratory infections, asthma, reduced lung function, and development of adult lung diseases (e.g., cancer and COPD) (1).

Objective: To elucidate the impact of lack of Palivizumab administration during off-season RSV periods on the RSV-related hospitalization among 29-34 weeks of gestational age (wGA) preterm infants. We utilized the summer of 2021 off-season RSV surge during the COVID19 pandemic. Methods: This multi-center retrospective observational study was conducted in 11 medical centers across Israel. We included infants > 1 year-old hospitalized with RSV infection between November 2017-August 2021. Patients were categorized into an in-season admissions group (November-March) and off-season admissions group (April-October). The primary outcome was the proportion of RSV hospitalizations among 29-34wGA infants in relation to total RSV admissions during the same season. Secondary outcomes included clinical severity parameters. Results A total of 3,296 infants were admitted during the RSV season, and 1,044 during the off-season. The proportion of 29-34wGA preemies was significantly higher in the off-season group compared to the in-season group (7% vs 2.1%, p<0.001). In the off-season group, we observed a significantly higher proportion of Jewish individuals (80.1% vs. 59.2%, p=0.001) and higher socioeconomic status (55.1% vs. 45.1%, p<0.001) compared to the in-season group. In the multivariable logistic-regression model, off-season hospitalization odds for 29-34 wGA preemies were significantly higher (2.6-fold, 95% CI:1.8-3.9, p<0.001) compared to in-season, irrespective of demographic covariates. Similar clinical severity parameters was observed between the groups. Conclusions Our results revealed a significantly higher proportion of infants born at 29-34 wGA among those hospitalized during off-season periods compared to in-season periods. These findings highlight the importance of including 29-34 wGA infants into future RSV immunoprophylaxis recommendations.

To the editor:

Background It remains unclear if pediatric patients with acute or chronic lung diseases benefit from chest physiotherapy (CPT) during spontaneous breathing. The electrical impedance tomography (EIT) offers the opportunity to assess treatment effects of CPT on regional ventilation distributions. Methods We conducted a prospective feasibility study between 10/2023 to 05/2024. Pediatric patients with need for active or passive CPT were screened. EIT measurements were performed at (T1) immediately prior to CPT intervention, and (T2) within 30 minutes after CPT intervention. Results Overall, 25 patients were enrolled, with two patients enrolled twice at different admissions, resulting in 54 EIT-measurements. The mean horizontal center of ventilation (CoVx) and the mean vertical CoVy were equally distributed at T1 and T2, without any difference seen when subdividing for mode of CPT. The mean global inhomogeneity index (GI) decreased from 0.38 to 0.36 (∆GI: -6%, p=0.939) in the overall cohort, with a significant decrease between T1 and T2 in patients with active (∆GI: -10%, p=0.015), but not in patients with passive CPT (∆GI: +6%, p=0.199). In patients with a localized pulmonary finding in the radiologic assessment (n=10) we observed a markedly increase of the proportional ventilation distribution of the affected lung side after CPT (T1:44% vs. T2: 48%, p=0.057). Conclusion EIT seems feasible to monitor changes in regional ventilation distribution after CPT in pediatric patients. Patients with localized pulmonary radiological findings and patients after active CPT seems to benefit most from CPT, whereas there is a subset of individuals with no response to CPT.

Introduction – Uncontrolled asthma is common in children and is associated with a decline in lung function. Repeated personalised assessments of the reasons for inadequate control should including evaluations of the patients’ surroundings. This can be support by Indoor Environmental Advisors (IEAs). This cohort study aimed to assess the impact on asthma control of routine assessment of children’s home by IEAs. Methods – Children aged 4 to 18 years who had asthma severity grades of 3 to 5 according to Global Initiative for Asthma guidelines were enrolled. Asthma control was evaluated using the standardized Asthma Control Test (ACT) before and 3 months after the IEA visit. Results – We enrolled 15 children with moderate-to-severe asthma. Asthma control improved significantly after the IEA visit (p=0.004). The percentage of children with uncontrolled asthma decreased from 64.3% before IEA visit to 27.3% at 3 months, and none of the patients had 2 exacerbations or more within the 3 months after the visit. IEA identified environmental issues whose remediation could likely contribute to improve asthma control. However, there are still barriers to the implementation of IEA that would be beneficial to remove. Conclusion – Our results support the inclusion of IEA interventions as part of the standard care pathway for children with asthma.

home NIV for children must consider the key role of the interface, in addition to selecting the ventilatory mode and settings. Acceptance and adherence to NIV often depend on the time spent selecting the right mask, as well as on regular and careful attention to preventing and addressing various issues that arise during NIV

last year's publications constitute an important step in the care of children with oSDB. The time has come to abandon the sacrosanct Apnea-Hypopnea Index as the sole marker on which we base all decisions for managing children with oSDB. We are entering a new era where better phenotyping of oSDB in children will enable personalized medicine

While the diagnosis of cystic fibrosis (CF) is often straightforward and reliant on correlation between genetic testing and clinical signs and symptoms, there is a subset where the distinction is not nearly as clearcut. This has previously been reported in patients identified through newborn screening but not meeting full CF diagnostic criteria, earning the label of CF Screen Positive, Inconclusive Diagnosis (CFSPID) instead. A homologous diagnostic category in adults is named CF Transmembrane Conductance Regulator-Related Disorder (CFTR-RD). Through a retrospective chart review, this study reports on a relatively large adult cohort (n=23) that presented to pulmonology clinic at a single center with intermediate or positive sweat chloride tests but non-diagnostic full CFTR gene analysis. Median sweat chloride result was 48 mmol/L, and a majority of the cohort had chronic lung disease with atypical pathogens on sputum culture, including Pseudomonas aeruginosa, non-tuberculous Mycobacteria, Acinetobacter species, amongst others. This clinical picture suggests CFTR dysfunction or similar mechanism in the absence of an identified genetic cause. Alternate chloride channels and their respective genes or candidates of genetic modifiers to the CF-phenotype could be targets of further research in this cohort or similar patients. Such genetic modifiers include loci that have been implicated in inflammation, the CFTR interactome, and/or co-/post-translational modification of CFTR.