Noga Arwas

Background: Vaccines are a cornerstone of modern medicine, however, in some regions, low coverage is reported in patients with chronic diseases, including people with cystic fibrosis (pwCF), compared to the general population. Methods: This retrospective multicenter study in Israel included pwCF born after January 1, 2000, and compared them to the general population. Vaccination data were collected from patient databases and the Ministry of Health reports for the general population. Results: Out of 269 eligible pwCF aged 6 months to 23 years, a total of 173 were included. Coverage for the initial DTaP‐IPV‐HiB vaccine, administered in the first year of life, was similar between pwCF and the general population (92% compared with 96%, p = 0.23). In contrast, coverage for other routine vaccines given in the first year of life was significantly lower in pwCF: HAV (76% compared with 92%), HBV (85% compared with 96%), and the first dose of MMRV (85% compared with 97%) (all p < 0.001). Booster dose coverage for DTaP‐IPV‐HiB and MMRV, given at age 6–7 years, was also significantly reduced in pwCF (72% compared with 95% and 68% compared with 96% respectively, p < 0.001). Pneumococcal conjugate vaccine uptake was significantly lower in pwCF (61.8% vs. 94% in the general population p < 0.001), while the 23‐valent pneumococcal vaccine was slightly more prevalent among pwCF compared to those with other chronic conditions, although uptake was low in both groups (15% vs. 10%, p = 0.001). Influenza vaccination rates during 3 seasons were significantly higher in pwCF (65%–70% vs. 20‐27% in the general population, p < 0.001), whereas COVID‐19 vaccine uptake was lower in adolescent pwCF compared to their general population peers (38.5% vs. 57.4%, p = 0.04). Conclusion: Our study highlights suboptimal vaccine coverage among pwCF, particularly after the first year of life, affecting both routine early‐life vaccines and booster doses. Greater awareness and proactive measures are needed to ensure adequate vaccination.

Interleukin‐6 receptor (IL‐6R) deficiency is a rare immunodeficiency marked by impaired IL‐6 signaling, affecting the inflammatory response and respiratory health. In this report, pediatric patients with IL‐6R deficiency presented with a spectrum of respiratory symptoms, from mild to severe infections, but did not commonly develop early bronchiectasis. Due to the absence of typical inflammatory markers in lung infections, routine imaging is advised to monitor for potential complications, even in the absence of overt clinical signs.

Children with Down syndrome (DS) often experience recurrent and prolonged hospitalizations from respiratory infections. While Azithromycin has been increasingly used for lower-respiratory tract infections (LRTIs) in children, its potential benefits for DS patients are unexplored. This study evaluates the effect of chronic azithromycin treatment on respiratory morbidity in children with DS. In this retrospective cohort study, we analyzed data from children with DS aged 0–6 years treated with Azithromycin for at least 6 weeks (10 mg/kg, thrice weekly). Respiratory morbidity indicators, such as primary care visits, medication consumption, emergency department visits, hospitalizations, and hospital length of stay (LOS), were assessed and compared six months before and after the Azithromycin treatment. Twenty-three episodes of Azithromycin treatment (≥ 6 weeks) in eighteen children with DS (mean age of 2.3 years, 78% males) during 2016–2023 were included. A significant reduction in mean respiratory LOS was observed (13.6 vs. 4.7 days, p = 0.05) when comparing pre to post-Azithromycin treatment. Other secondary respiratory outcomes showed no significant differences. The significant reduction in respiratory LOS suggests the potential benefits of Azithromycin in children with DS, and emphasizes the need for larger clinical trials to determine optimal use and long-term effects in this vulnerable population.

Bronchopulmonary dysplasia (BPD) poses a significant challenge as the most common late morbidity of preterm infants. This study aimed to evaluate airway abnormalities in infants with BPD who underwent flexible bronchoscopy (FB) to gain insights into the prevalence of upper airway obstruction and associated complications. A retrospective case–control study was conducted on BPD patients who underwent FB at a tertiary center between 2013 and 2023. BPD patients were matched (1:3) with a reference group based on age, gender, and ethnicity, who also had undergone FB. Demographic data, comorbidities, indications for FB, findings, and complications during and after FB were collected. The study included 50 BPD patients (mean age 1.26 ± 0.9 years, 58% males), and 150 controls. As expected, BPD patients had a lower gestational age, lower birth weight, and longer hospitalizations and were treated with more medications. Abnormal bronchoscopy findings were significantly more common in the BPD group compared to the reference group, with an increased rate of turbinate hypertrophy (OR [95% CI]: 3.44 [1.27–9.37], P = 0.014), adenoid hypertrophy (OR: 2.7 [1.38–5.29], P = 0.004), lingual tonsils (OR: 5.44 [1.29–27.4], P = 0.0024), subglottic stenosis (OR: 6.95 [2.08–27.1], P = 0.002), and tracheomalacia (OR: 2.98 [1.06–8.19], P = 0.034). Complications including desaturation (OR: 3.89 [1.32–11.7], P = 0.013) and PICU admission (OR: 16.6 [2.58–322], P = 0.011) were more frequent in the BPD than in the reference group. Conclusion: The study revealed a high prevalence of structural anomalies leading to upper airway obstruction and complications in infants with BPD undergoing FB. These findings emphasize the importance of careful consideration and preparation for bronchoscopic procedures in this vulnerable population. What is known: • Bronchopulmonary dysplasia (BPD) represents the most prevalent late morbidity among preterm infants. • Preterm infants diagnosed with BPD frequently undergo diagnostic procedures, including flexible and rigid bronchoscopies, to identify structural pathologies within the respiratory tract. What is new: • A significantly higher prevalence of structural anomalies leading to upper airway obstruction was observed in the BPD group compared to controls. • The incidence of complications during flexible bronchoscopy was higher in the BPD group than in controls.

Though PCD usually presents after birth in term neonates, diagnosing PCD during the neonatal and infancy stages is uncommon, particularly in children who do not exhibit laterality defects. We report our recent experience with the diagnosis of PCD in the neonatal and early infantile period in a highly consanguine population. This was achieved by implementing a novel genetic-based diagnostic approach based on direct testing for recognized regional genetic variants. We conducted a retrospective analysis of children diagnosed with PCD at Soroka University Medical Center during the neonatal or early infantile period between 2020 and 2023. We included children under 3 months of age who had a genetic confirmation of PCD, as evidenced by the presence of two pathogenic variants in recognized genes. Genetic testing targeted regional genetic variants in previously identified PCD genes. Eight patients were included. The median age at diagnosis was 12.5 days. Three (38%) were born prematurely < 34 weeks gestational age. All patients were presented with respiratory distress and hypoxemia after birth. The median duration of oxygen support was 23 days, and upper lobe atelectasis was present in five patients (63%). Congenital cardiac malformation was present in four patients. Organ laterality defects were present in four patients. Genetic mutations identified were in the DNAAF5, DNAL1, DNAAF3, and DNAH1 genes.      Conclusion: Neonatal diagnosis of PCD is uncommon, especially in atypical presentations such as children without laterality defects or preterms. Focusing on a genetic diagnosis of the local tribal pathogenic variants promotes a potential cost-efficient test leading to earlier diagnosis. There is a need for a standardized protocol for earlier diagnosis of PCD in high-consanguinity areas. What is Known: • Primary ciliary dyskinesia (PCD) typically presents after birth in term neonates. • Diagnosing PCD during neonatal and infancy stages is challenging, particularly in children without laterality defects. What is New: • A novel genetic-based diagnostic approach was implemented on the neonatal population in a highly consanguine community, focusing on direct testing for regional genetic variants, leading to early and rapid diagnosis of PCD.

Thermal epiglottitis, a non-infectious cause of epiglottitis, is a rare entity that shares some clinical features with infectious epiglottitis. This study presents 16 years of experience in diagnosing and managing thermal epiglottitis. A retrospective descriptive study in a tertiary center in southern Israel included confirmed cases of thermal epiglottitis in children (0–18 years) between 2004 and 2020 by endoscopy. Of approximately 600,000 pediatric ER admissions between 2004 and 2020, seven children were diagnosed by endoscopy with thermal epiglottitis (mean age 24 months, 71% males). Clinical presentation included stridor, respiratory distress, and drooling. Four children had fever and elevated inflammatory markers at presentation and were treated with systemic antibiotics. All were treated with systemic steroids. The median length of stay in the PICU was five days, and four patients required intubations. All fully recovered without experiencing any sequelae.   Conclusion: Thermal epiglottitis stands as a potential contributor to acute upper airway obstruction. Although it’s rarity, it should be discussed in any child with acute upper airway obstruction. It is essential to inquire directly about the accidental intake of hot beverages, particularly in cases lacking fever or elevated inflammatory markers. What is Known: • Thermal epiglottitis is a rare, non-infectious condition sharing clinical features with infectious epiglottitis. • Common presentations include stridor, respiratory distress, and drooling. What is New: • Thermal epiglottitis is a potential contributor to acute upper airway obstruction, urging consideration even in the absence of fever or elevated markers. • Direct inquiry about hot beverage intake for diagnosis is essential for diagnosis.

Background: Children with Down syndrome (DS) often undergo flexible bronchoscopies (FB) due to common respiratory symptoms. Objective: To examine the indications, findings and complications of FB in pediatric DS patients. Methods: A retrospective case-control study on FB performed in DS pediatric patients between 2004-2021 in a tertiary center. DS patients were matched to controls (1:3) based on age, gender and ethnicity. Data collected included demographics, comorbidities, indications, findings and complications. Results: Fifty DS patients (median age 1.36 years) and 150 controls (median age 1.27 years) were included. Obstructive sleep apnea evaluation and oxygen dependence were more common indications among DS (38% vs. 8%, 22% vs. 4%, p<0.01, respectively). Normal FB was less frequent in DS compared with controls (8% vs. 28%, p=0.01). Soft palate incompetence and tracheal bronchus were more frequent in DS (12% vs. 3.3%, p=0.024, 8% vs. 0.7%, p=0.02, respectively). Complications were more frequent in DS (22% vs.9.3%, IRR 2.36, p=0.028). In DS, cardiac anomalies (IRR 3.96, p<0.01), pulmonary hypertension (PHTN) (IRR 3.76, p=0.006), and PICU hospitalization before the procedure (IRR 4.2, p<0.001) were associated with higher complication rates. In a multivariate regression model, history of cardiac disease and PICU hospitalization before the procedure, were independent risk factors for complications with an IRR of 4 and 3.1, respectively (p=0.006, p=0.05). Conclusion: DS pediatric patients undergoing FB are a unique population with specific indications and findings. DS patients with cardiac anomalies and PHTN are at the highest risk for complications.

Background: Asthma is the most common chronic respiratory disease in children. The neutrophil-to-lymphocyte ratio (NLR) is a marker of a chronic inflammatory state, however, data on the predictive role of NLR in acute asthma exacerbations in children is lacking. Aim: To investigate the potential role of NLR in predicting the severity of acute asthma exacerbations in children. Methods: A retrospective study, that included children aged 2-18 years, who were referred to the emergency department (ED) due to asthma exacerbation, between 2016 and 2021, and underwent a complete blood count upon arrival. NLR was assessed as a continued variable and divided into four quartiles. Association was examined between severity parameters and NLR quartiles. Results: Eight hundred thirty-one ED visits for asthma exacerbation were included in the study. The median NLR was 1.6, 3.8, 6.7, and 12.9 in quartiles 1,2,3, and 4, respectively (p<0.001). Demographic parameters, background diseases, and chronic medications were similar between the quartiles. Higher heart rate, body temperature, systolic blood pressure, and respiratory rate were observed in the higher NLR quartiles, as well as lower oxygen saturation. Higher urgency scale and medical treatment, including intravenous Magnesium sulfate, were observed in the higher NLR quartiles, with higher admission rates and prolonged hospitalizations. Conclusion: NLR upon admission reflects the severity of asthma exacerbation and the chances of hospitalization among children in the ED. Further studies are warranted for its implementation in the clinical setting, providing validated cutoff values in which a high probability of severe asthma is likely.

Asthma is the most common chronic respiratory disease in children. The neutrophil-to-lymphocyte ratio (NLR) is a marker of a chronic inflammatory state; however, data on the association of NLR with acute asthma exacerbations in children is lacking. In this cross-sectional study, between 2016 and 2021, children aged 2–18 years who were referred to the emergency department (ED) due to asthma exacerbation, were included. NLR, calculated from complete blood count upon arrival, was assessed as a continuous variable and was classified into four groups according to quartiles. The association between severity parameters and NLR quartiles was examined. A total of 831 ED visits for asthma exacerbation were included in the study. The median NLR was 1.6, 3.8, 6.7, and 12.9 in quartiles 1–4, respectively (p < 0.001). Demographic parameters, background diseases, and chronic medications were similar between the quartiles. Higher heart rate, body temperature, systolic blood pressure, and respiratory rate were observed in the higher NLR quartiles, as well as lower oxygen saturation. Higher urgency scale and higher rates of intravenous magnesium sulfate were observed in the higher NLR quartiles, with higher admission rates and prolonged hospitalizations. In summary, NLR upon admission is associated with the severity of asthma exacerbation and higher chances of hospitalization among children in the ED.