The role of bronchial challenge test in guiding therapy in preschool children with atypical recurrent respiratory symptoms.

OBJECTIVE: This retrospective observational cohort study aimed to assess the real-life application of bronchial challenge test (BCT) in the management of preschool children presenting with atypical recurrent respiratory symptoms (ARRS). METHODS: We included children aged 0.5-6 years referred to a pediatric-pulmonology clinic who underwent BCT using methacholine or adenosine between 2012 and 2018 due to ARRS. BCT was considered positive based on spirometry results and/or wheezing, desaturation, and tachypnea reactions. We collected data on demographics, BCT results, pre-BCT and post-BCT treatment changes, and 3-6 months post-BCT compliance and symptom control. The primary outcome measure was the change in treatment post-BCT (step-up or step-down). RESULTS: A total of 228 children (55% males) with a mean age of 4.2 ± 0.6 years underwent BCT (52% adenosine-BCT, 48% methacholine-BCT). Children referred for methacholine were significantly younger compared with adenosine (3.6 ± 1.2 vs. 4.2 ± 1.2 years, p < .01). Methacholine and adenosine BCTs were positive in 95% and 61%, respectively. Overall, changes in management were observed in 122 (53.5%) children following BCT, with 83 (36.4%) being stepped up and 37 (17%) being stepped down. Significantly more children in the methacholine group were stepped up compared with the adenosine group (46% vs. 28%, p = .004). During the follow-up assessment, we observed a clinical improvement in 119/162 (73.4%) of the children, with nearly 87% being compliant. CONCLUSION: This study demonstrates the importance of BCT in the management of preschool children presenting to pediatric pulmonary units with ARRS. The change in treatment and subsequent clinical improvement observed highlight the added value of BCT to the pulmonologist.

Higher Rates of Hospitalizations among Pediatric Refugees than Local Population Attending the Emergency Department and Longer In-patient Stay.

BACKGROUND: The global refugee crises have raised concerns among medical communities worldwide; nonetheless, access to healthcare has rarely been studied even though refugees are a medically high-risk group. OBJECTIVES: To compare pediatric department admission rates from the pediatric emergency department (PED) of refugees and Israelis. METHODS: We compared data from refugee and Israeli children admitted to the pediatric department at Wolfson Medical Center in Israel between 2013-2017. RESULTS: A total of 104,244 patients (aged 0-18 years) came to the PED. Admission rate to the pediatric department for refugees was 695/2541 (27%) compared to 11,858/101,703 (11.7%) Israeli patients (P < 0.001). Hospital stay for patients 0-2-years of age was 3.22 ± 4.80 days for refugees vs. 2.78 ± 3.17 for Israelis (P < 0.03). Re-admission rate within 7 days was 1.3% for refugees and 2.6% for Israelis (P < 0.05). Dermatological diseases (e.g., impetigo and cellulitis) were more frequent in refugees (23.30% vs. 13.15%, P < 0.01); however, acute gastroenteritis and respiratory diagnoses were more common in Israelis (18.52% vs. 11.72%, P < 0.05 and 14.84% vs. 6.26%, P < 0.01, respectively). Neurological diseases (e.g., febrile convulsions) were also more frequent in Israelis (7.7% vs. 3%, P < 0.05). Very significantly, 23% of refugees had no healthcare coverage, while only 0.2% of the Israelis had none (P < 0.001). CONCLUSIONS: We found significant morbidity in refugees compared to the local Israeli pediatric population, highlighting the need for different approaches for each population.

Risk Factors and Characteristics of Candidemia After Cardiac Surgery in Pediatric Patients in Central Israel.

BACKGROUND: Candidemia is a serious complication in pediatric patients with congenital heart defects (CHD) after cardiac surgery. Information about the epidemiology, clinical characteristics and risk factors for candidemia in this vulnerable population remains limited. METHODS: This retrospective case-control study was conducted in 2 pediatric intensive care units between 2004 and 2019. All patients <18 years old who developed candidemia following cardiac surgery were included. Each case was matched with 2 control patients based on age and date of surgery. Multivariable logistic regression analysis was conducted to determine the risk factors for postoperative candidemia. RESULTS: Thirty-five candidemia cases were identified and matched to 70 control cases. The incidence of candidemia was 6.3 episodes per 1000 admissions. The median age for candidemia cases was 4 months. The attributable mortality was 28.5%. The predominant (54%) pathogens isolated were non- albicans Candida species, of which C. parapsilosis isolates demonstrated high resistance to fluconazole (70%). Independent risk factors associated with candidemia included cumulative antibiotic exposure for ≥4 days [OR: -4.3; 95% confidence interval (CI): 1.3-14.6; P = 0.02], the need for total parenteral nutrition or peritoneal dialysis (OR: -6.1; 95% CI: 2-18.8; P = 0.001), male sex (OR: 6.2; 95% CI: 1.9-20.3; P = 0.002) and delayed sternal closure≥2 days (OR: -3.2; 95% CI: 1-11.2; P = 0.05). CONCLUSIONS: Postoperative candidemia in children with CHD is an uncommon but severe complication. Our study revealed an unexpectedly high frequency of fluconazole-resistant C. parapsilosis as the main cause of non- albicans candidemia. In addition to confirming previously recognized risk factors, our results reveal new potential risk factors such as delayed sternal closure and male sex.

Bronchoscopy in the management of children from developing countries undergoing congenital heart surgery.

OBJECTIVES: To study the clinical characteristics and impact of bronchoscopy in children from developing countries, referred for cardiac surgery, through the "Save a Child's Heart" (SACH) organization. METHODS: We performed a retrospective hospital-chart review of SACH children (0-18 years old) referred between 2006 and 2021 who underwent fiberoptic bronchoscopy. We examined demographics, congenital-heart-disease (CHD) types, bronchoscopy's indications and findings, subsequent recommendations, number of ventilation, and intensive-care-unit days. The primary outcome was percent changes in management and diagnosis, following the bronchoscopy. We included a control group matched-for-age and CHD type, who did not undergo bronchoscopy. RESULTS: We performed 82 bronchoscopies in 68 children: 18 (26.5%) preoperatively; 46 (67.6%) postoperatively; and four (5.9%) both. The most prevalent CHDs were Tetralogy-of-Fallot (27.9%) and ventricular-septal-defect (19.1%). The main indications were persistent atelectasis (41%) and mechanical ventilation/weaning difficulties (27.9%). Bronchoscopic evaluations revealed at least one abnormality in 51/68 (75%) children. The most common findings were external airway compression (23.5%), bronchomalacia (19.1%), and mucus secretions (14.7%). Changes in management were made in 35 (51.4%) cases, with a major change made in 14/35 (40%) children. Compared to the control group, the children undergoing bronchoscopy were both ventilated longer (median 6 vs. 1.5 days, p < 0.0001) and stayed longer in the intensive care unit (median 1.5 vs. 18.5 days, p < 0.0001). CONCLUSION: A bronchoscopy is an important tool in the diagnosis and management of the unique group of children from developing countries with CHD referred for cardiac surgery. The results of our study, reveal a more complicated clinical course in children requiring bronchoscopy compared to controls.

The impact of the COVID-19 pandemic on respiratory morbidity during infancy: A birth-cohort study.

OBJECTIVE: To evaluate the incidence of wheezing and overall respiratory morbidity in healthy infants born during the first peak of the coronavirus disease-2019 (COVID-19) pandemic, compared with infants born during the preceding year. METHODS: This was a single-center retrospective birth cohort study to compare a cohort of children born between February and March 2020 (COVID-19 group) to a control group of children born between February and March 2019 (pre-COVID-19 group). At 1 year of age, we collected respiratory data using parental and telephone questionnaires. PRIMARY OUTCOME: wheezing incidence and/or bronchodilator use. SECONDARY OUTCOMES: recurrent wheezing, emergency-room visits, hospital admissions, pneumonia diagnosis, and admissions due to lower-respiratory-tract-infections (LRTI). We included the following covariate risk factors in the logistic regression models; atopy, daycare attendance, breastmilk feeding, parental smoking, C-section, siblings, and gestational age. RESULTS: We enrolled 588 infants, 294 in each group (48% males). Demographic, perinatal, and atopic characteristics were similar between the groups. Compared to the pre-COVID-19 group, infants born during the COVID-19 period were significantly less likely to report wheezing and/or bronchodilator use (adjusted-odds ratio [OR], 0.4; 95% confidence interval [CI] 0.28-0.59), systemic steroid use, (adjusted-OR, 0.47; 95% CI 0.24-0.91), emergency-room visits (adjusted-OR, 0.36; 95% CI 0.17-0.72), LRTI admissions (adjusted-OR, 0.2; 95% CI 0.05-0.74), or pneumonia diagnosis (adjusted-OR, 0.22; 95% CI 0.09-0.53). CONCLUSIONS: This study investigated wheezing and respiratory morbidity over the first year of the COVID-19 pandemic in infants born during the first peak of COVID-19. The study demonstrated a significant decrease in most aspects of respiratory morbidity. A longitudinal follow-up study to explore the subsequent impact of these findings is warranted.

Can bronchial challenge test with adenosine or methacholine at preschool age predict school-age asthma?

OBJECTIVE: Bronchial challenge test (BCT) measures current airways-hyperreactivity, however, its predictive role in pre-school children (<6 years) for the diagnosis of asthma at school age is still debatable. We aimed to find whether preschool children with a positive adenosine or methacholine BCT are more prone to asthma at school age. METHODS: We included children aged 6-13 years with respiratory symptoms that were previously referred to our pulmonary function laboratory for BCT (methacholine or adenosine, depending on the question asked) at age 10 months to 6 years (baseline). BCT was considered positive based on spirometry results or wheezing, desaturation, and tachypnea reactions. The primary outcome measure was asthma diagnosis at school age using the well-validated International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. We used logistic regression analysis to explore whether positive BCT could predict school-age asthma while including age and collected modified asthma predictive index in the model. RESULTS: One hundred and fifty-one of 189 children (53% males), completed the ISAAC questionnaire (response rate = 80%). Mean ages at BCT and at follow-up were 3.9 ± 1.28 and 9.4 ± 1.85 years, respectively. At baseline, 40 of 67 had a positive adenosine test and 73 of 84 had a positive methacholine BCT. Thirty-nine children were diagnosed with asthma at school age. Logistic regression analysis showed that a positive adenosine test at pre-school age was the best predictor, significantly increasing the odds of asthma at school age by 6.34 (95% CI: 1.23-32.81, p = .028), while methacholine did not show significance (p = .69). CONCLUSION: Choosing the relevant BCT for the question asked, positive adenosine, but not methacholine test, at pre-school, may predict asthma at school age.

The Sesame-Peanut Conundrum in Israel: Reevaluation of Food Allergy Prevalence in Young Children.

BACKGROUND: Food allergies (FAs) are on the rise worldwide. A previous cross-sectional study from 2002 in Israel estimated the prevalence of IgE-mediated FA among young children at 0.85%. Although sesame was found to be a common allergen, peanuts were found to be a rare allergen. OBJECTIVE: To determine the prevalence and distributions of IgE-mediated FAs among young children in Israel compared with previous data. METHODS: A total of 1932 young children (56% males, 44% females) with a mean age of 22.4 months (range, 18-30 months) were sequentially recruited from 15 government family health care centers in north Israel. Parents completed a questionnaire with 2 screening questions for suspected FA. Subjects with suspected FA underwent further evaluation including telephone interview, skin prick tests, and oral food challenge as needed. RESULTS: After analyzing the questionnaires, 146 subjects were suspected to have FA. Seventy-nine subjects were excluded by telephone interview and 13 were excluded on the basis of negative oral food challenge. We identified 54 of 1932 (2.8%) young children with 75 IgE-mediated FAs. Thirty-nine of 54 (72.2%) had allergy to 1 food and 9 (16.6%) to 2 foods. The most common food allergens were cow's milk (1%), eggs (0.88%), sesame (0.93%), tree nuts (0.57%), peanuts (0.2%), and fish (0.2%). CONCLUSIONS: The prevalence of IgE-mediated FA among young children in Israel has increased dramatically from 0.85% to 2.8%. The relative prevalence of the most common food allergens is similar to that identified in 2002, with a high prevalence of sesame FA and low prevalence of peanut FA.

Evaluation of clinically and physiologically atypical asthma: If it doesn't wheeze it may still be asthma.

OBJECTIVE: Children with asthma-like symptoms may not clinically wheeze. The objectives of this study were to evaluate if children, without physician-documented wheeze, wheeze during bronchial-challenge-testing (BCT), and if measurements of O2Sat and respiratory rate during BCT improve the BCT sensitivity? METHODS: Seven hundred and twenty-four children, who were referred for suspicion of asthma, performed a BCT. Positive BCT was determined by the provocation concentration (PC) which resulted in a 20% decrease in FEV1 (PC20), (in those who were able to perform spirometry, group B), or (in those unable to perform spirometry, group A) a 50% increase in respiratory rate (PCRR), or a 5% decrease in oxygen-saturation (PCO2-Sat) or appearance of wheezing (PCwheeze). RESULTS: Five hundred and seven BCTs were positive: group A n = 89 age, median (IQR), 3 (2.5-3.7) years (17.6%), were unable to perform spirometry, and group B n = 418 age 10.7 (6.8-15.6) years (82.4%), were able to perform spirometry. Children, without physician-documented wheeze in the total population (groups A plus B), were more likely (65.5%) to have a positive BCT without wheeze compared with those with physician-documented wheeze (41.0%, P < 0.001). In group A, adding PCRR and PCO2-Sat increased BCT sensitivity by 23.6%. CONCLUSIONS: Many children in both groups did not wheeze despite reaching BCT endpoints. Children without physician-documented wheeze tended not to wheeze at BCT. This may result in clinical under-diagnosis of asthma if depending on the presence of wheeze. In young children, adding PCRR and PCO2-Sat substantially increases BCT sensitivity and may improve asthma diagnosis.

Homemade Hypertonic Saline: Essential Treatment Can Be Available and Affordable.

BACKGROUND: Nebulized hypertonic saline (HS) treatment is unavailable to large populations worldwide. OBJECTIVES: To determine the bacterial contamination and electrolyte concentrations in homemade (HM-HS) vs. pharmacy made (PM-HS). METHODS: We conducted three double-blind consecutive trials: 50 boiled-water homemade 3%-HS (B-HM-HS) bottles and 50 PM-HS. The bottles were cultured after 48 hours. Electrolyte concentrations were measured in 10 bottles (5 per group). Forty bottles (20 per group) were distributed to volunteers for simulation of realistic treatment by drawing 4 ml HS three times daily. From each bottle, 4 ml samples were cultured after 1, 5, and 7 days. Volunteers prepared 108 bottles containing 3%-HS, sterilizing them using a microwave oven (1100-1850W). These bottles were cultured 24 hours, 48 hours, and 1 month after preparation. RESULTS: Contamination rates of B-HM-HS and PM-HS after 48 hours were 56% and 14%, respectively (P = 0.008). Electrolyte concentrations were similar: 3.7% ± 0.4 and 3.5% ± 0.3, respectively (P = NS). Following a single day of simulation B-HM-HS bottles were significantly more contaminated than PM-HS bottles: 75% vs. 20%, respectively (P < 0.01). By day 7, 85% of PM-HS bottles and 100% of B-HM-HS bottles were contaminated (P = 0.23). All 108 microwave-oven prepared bottles (MICRO-HS) were sterile, which was significantly better than the contamination rate of B-HM-HS and PM-HS (P < 0.001). Calculated risk for a consecutive MICRO-HS to be infected was negligible. CONCLUSIONS: Microwave preparation provides sterile HS with adequate electrolyte concentrations, and is a cheap, fast, and widely available method to prepare HS.

Collecting clinical data in primary ciliary dyskinesia- challenges and opportunities.

Rationale: Primary ciliary dyskinesia (PCD) is under diagnosed and underestimated. Most clinical research has used some form of questionnaires to capture data but none has been critically evaluated particularly with respect to its end-user feasibility and utility. Objective: To critically appraise a clinical data collection questionnaire for PCD used in a large national PCD consortium in order to apply conclusions in future PCD research. Methods: We describe the development, validation and revision process of a clinical questionnaire for PCD and its evaluation during a national clinical PCD study with respect to data collection and analysis, initial completion rates and user feedback. Results: 14 centers participating in the consortium successfully completed the revised version of the questionnaire for 173 patients with various completion rates for various items. While content and internal consistency analysis demonstrated validity, there were methodological deficiencies impacting completion rates and end-user utility. These deficiencies were addressed resulting in a more valid questionnaire. Conclusions: Our experience may be useful for future clinical research in PCD. Based on the feedback collected on the questionnaire through analysis of completion rates, judgmental analysis of the content, and feedback from experts and end users, we suggest a practicable framework for development of similar tools for various future PCD research.

Primary ciliary dyskinesia in Israel: Prevalence, clinical features, current diagnosis and management practices.

BACKGROUND: Primary Ciliary Dyskinesia (PCD) is rare and its features in Israel have not been described. AIMS: to assess prevalence utilizing state-of-the-art diagnostic techniques, and describe clinical features, diagnostic and management practices in Israel. METHODS: A national multicenter study from 2012 to 2013 recruited patients diagnosed or suspected of having PCD. Diagnosis was verified using: nasal Nitric Oxide (nNO); High-speed Video Microscope Analysis (HVMA); Transmission Electron Microscopy (TEM) of cilia; Immuno-fluorescence staining (IF) for ciliary proteins, and genetic analysis. RESULTS: Of the 203 patients recruited from 14 pediatric centers, 150 had a PCD diagnosis verified. Median age was 15.05y, with range 0.15-60.5y. PCD prevalence was 1:54,000 for the general population and 1:25,000 in children (5-14 y). For the non-Jewish (mainly Druze and Arab Moslem) compared to Jewish populations, prevalence was 1:16,500 and 1:139,000 respectively (p < 0.0001) and parental consanguinity was 85.4% and 21.9% respectively (p < 0.0001). Clinical features included bronchiectasis (88%), rhinitis (81%), recurrent pneumonia (78%), recurrent otitis (62%), neonatal pneumonia (60%) and situs inversus (42%). Prior diagnostic practices varied widely between centers with TEM assessed in 55% and abnormal in 61% of these. Management included antibiotics and airway clearance. Diagnostic verification revealed for 150 PCD patients: 81% nNO<233 ppb, 62% abnormal HVMA, 51% diagnostic TEM, 58% diagnostic IF and, 57% genetic diagnosis. CONCLUSIONS: PCD in Israel is rare, with comprehensive diagnostic tests showing prevalence in children similar to Europe. Prevalence was higher in non-Jews, associated with parental consanguinity. Diagnostic and management practices vary. Referral centers providing comprehensive diagnostic and care capabilities should be established.

Asthma-predictive-index, bronchial-challenge, sputum eosinophils in acutely wheezing preschoolers.

BACKGROUND: Most preschoolers with viral wheezing exacerbations are not atopic. AIM: To test in a prospective controlled trial whether wheezing preschoolers presenting to the ED are different from the above in three different domains defining asthma: the atopic characteristics based on stringent asthma predictive index (S-API), the characteristics of bronchial hyper-responsiveness (BHR), and airway inflammation. METHODS: The S-API was prospectively collected in 41 preschoolers (age 31.9 ± 17.4 months, range; 1-6 years) presenting to the ED with acute wheezing and compared to healthy preschoolers (n = 109) from our community (community control group). Thirty out of the 41 recruited preschoolers performed two sets of bronchial challenge tests (BCT)-(methacholine and adenosine) within 3 weeks and following 3 months of the acute event and compared to 30 consecutive ambulatory preschoolers, who performed BCT for diagnostic workup in our laboratory (ambulatory control group). On presentation, induced sputum (IS) was obtained from 22 of the 41 children. OUTCOMES: Primary: S-API, secondary: BCTs characteristics and percent eosinophils in IS. RESULTS: Significantly more wheezing preschoolers were S-API positive compared with the community control group: 20/41 (48.7%) versus 15/109 (13.7%, P < 0.001). All methacholine-BCTs-30/30 (100%) were positive compared with 13/14 (92.8%) in the ambulatory control group (P = 0.32). However, 23/27 (85.2%) were adenosine-BCT positive versus 3/17 (17.5%) in the ambulatory control group (P < 0.001). Diagnostic IS success rate was 18/22 (81.8%). Unexpectedly, 9/18 (50.0%) showed eosinophilia in the IS. CONCLUSIONS: Wheezing preschoolers presenting to the ED is a unique population with significantly higher rate of positive S-API and adenosine-BCT compared with controls and frequently (50%) express eosinophilic airway inflammation.

Massive pulmonary emboli in children: does fiber-optic-guided embolectomy have a role? Review of the literature and report of two cases.

Massive pulmonary emboli is a rare disease in children, with only 39 reported cases in the last 50 years. Almost 50% of the patients died suddenly without receiving medical treatment. Most of the patients who were managed medically (70% of the treated patients) underwent surgical pulmonary embolectomy with 80% survival. Surgical pulmonary embolectomy is a blind procedure that can be improved by using intraoperative angioscopy. This technique was reported in adults with good results. In this article, we describe two pediatric patients who underwent fiber-optic-guided surgical pulmonary embolectomy. To our knowledge, this technique has never been reported in the pediatric population.

Primary mucoepidermoid carcinoma of the trachea in a child.

Mucoepidermoid carcinoma of the trachea is a rare tumour, especially in the paediatric population. We report the case of a 9-year-old boy with mucoepidermoid carcinoma of the trachea that was preoperatively diagnosed as an intraluminal polypoid mass arising from the trachea and extending into the right main bronchus. A complete resection of the tumour with reconstruction and end-to-end anastomosis of the trachea was performed. The patient is now, 24 months after surgery, free of disease.

Hypertonic saline and acute wheezing in preschool children.

BACKGROUND: Most acute wheezing episodes in preschool children are associated with rhinovirus. Rhinovirus decreases extracellular adenosine triphosphate levels, leading to airway surface liquid dehydration. This, along with submucosal edema, mucus plaques, and inflammation, causes failure of mucus clearance. These preschool children do not respond well to available treatments, even oral steroids. This calls for pro-mucus clearance and prohydration treatments such as hypertonic saline in wheezing preschool children. METHODS: Randomized, controlled, double-blind study. Forty-one children (mean age 31.9 ± 17.4 months, range 1-6 years) presented with wheezing to the emergency department were randomized after 1 albuterol inhalation to receive either 4 mL of hypertonic saline 5% (HS) (n = 16) or 4 mL of normal saline (NS) (n = 25), both with 0.5 mL albuterol, twice every 20 minutes in the emergency department and 4 times a day thereafter if hospitalized. The primary outcome measured was length of stay (LOS) and the secondary outcomes were admission rate (AR) and clinical severity score. RESULTS: The LOS was significantly shorter in the HS than in the NS group: median 2 days (range 0-6) versus 3 days (range 0-5) days (P = .027). The AR was significantly lower in the HS than the NS group: 62.2% versus 92%. Clinical severity score improved significantly in both groups but did not reach significance between them. CONCLUSIONS: Using HS inhalations significantly shortens LOS and lowers AR in preschool children presenting with an acute wheezing episode to the emergency department.