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Objectives: Mucor within the airways of immunocompromised patients often signifies an invasive life-threatening infection. However, its significance in immunocompetent patients with chronic lung diseases is less clear. We aimed to assess the clinical implication of mucor in airway-secretion cultures of these patients., Methods: A single-center retrospective cohort study was performed. Patients with cystic fibrosis (CF), primary ciliary dyskinesia (PCD) or non-CF/non-PCD bronchiectasis followed in our Pediatric Pulmonary Institute, with sputum or bronchoalveolar lavage cultures growing Mucorales molds in the years 2010-2022, were included. Demographic and clinical parameters such as body mass index and spirometry values (forced expiratory volume at 1 second) were collected and compared with values up to 12 months prior to and following the index (positive culture) visit., Results: A total of 27 patients of whom 22 (82%) patients were with CF, 3 with PCD (11%) and 2 (7%) with non-CF/non-PCD bronchiectasis were included. Median age was 21.8 (14.9-32.1) years, with forced expiratory volume at 1 second of 62.8% ± 21.9% at the index visit. None of the patients developed disseminated disease, none had clinical or radiological evidence of fungal disease and none required antifungal therapy. Throughout the 12 months prior to and following the positive cultures, no significant changes were noted in body mass index, forced expiratory volume at 1 second, frequency of pulmonary exacerbations, days of hospitalization or days of antibiotic treatment., Conclusions: Evidence of mucor in airway cultures of immunocompetent patients with chronic lung disease does not necessarily signify clinical deterioration nor suggests invasive fungal disease. Larger, long-term prospective studies are required to obviate the need for a thorough evaluation in these patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Standard cardiopulmonary exercise testing (CPET) produces a rich dataset but its current analysis is often limited to a few derived variables such as maximal or peak oxygen uptake (V̇O 2 ). We tested whether breath-by-breath CPET data could be used to determine sample entropy (SampEn) in 81 healthy children and adolescents (age 7-18 years old, equal sex distribution). To overcome challenges of the relatively small time-series CPET data size and its nonstationarity, we developed a Python algorithm for short-duration physiological signals. Comparing pre- and post-ventilatory threshold (VT 1 ) CPET phases, we found: (1) SampEn decreased by 9.46% for V̇O 2 and 5.01% for V̇CO 2 (p < 0.05), in the younger, early-pubertal participants; and (2) HR SampEn fell substantially by 70.8% in the younger and 77.5% in the older participants (p < 0.001). Across all ages, females exhibited greater HR SampEn than males during both pre- and post VT 1 CPET phases by 14.10% and 23.79%, respectively, p < 0.01. In females, late-pubertal had 17.6% lower HR SampEn compared to early-pubertal participants (p < 0.05). Breath-by-breath gas exchange and HR data from CPET are amenable to SampEn analysis that leads to novel insight into physiological responses to work intensity, and sex and maturational effects., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Energy imbalance exposes athletes to relative energy deficiency in sports (REDs) syndrome. Data on energy consumption, REDs, and bone mineral density (BMD) in adolescent acrobatic gymnasts, especially in males, are scarce. Our aim was to examine the eating habits, energy balance, body composition, and BMD of these athletes. In this study, 18 healthy adolescents participating in competitive acrobatic gymnastics completed a questionnaire, underwent a dual-energy X-ray absorptiometry scan (DXA), received a food log, and had their activities monitored for 3 days. Eighteen acrobats were enrolled (mean age: 14.3 ± 1.2 years; males: 6/18). The mean total body BMD Z-score was 0.4 ± 1.0. Top-position acrobats (7/18) had significantly lower total body BMD Z-scores than base-positioned acrobats (-0.2 ± 0.3 vs. 0.8 ± 0.3, p = 0.032), though their forearms were not significantly different (0.2 ± 0.5 vs. 0.8 ± 0.7, p = 0.331). No sex differences were found for BMD Z-scores, BMI, or energy availability. The BMD parameters of the acrobats were within the normal range for a healthy pediatric population, although three had low BMDs (<-1 SD) for healthy athletes. Total body and LS BMD Z-scores were significantly lower in top-position athletes compared to base-position athletes. These findings suggest personalized (top vs. base) training programs (high-impact training) that may achieve better health outcomes.

Background: Several factors may influence quality of life (QOL) for patients with primary ciliary dyskinesia (PCD). We aimed to evaluate the association between pulmonary functions, nasal symptoms and QOL in PCD patients., Methods: A prospective single center study. Patients performed spirometry, whole body plethysmography, forced oscillation technique (FOT), lung clearance index (LCI), 6-min walk test (6MWT), and filled two questionnaires: a specific PCD QOL questionnaire (PCD-QOL) and Sino-nasal outcome test (SNOT-22) questionnaire, assessing symptoms of chronic rhinosinusitis and health related QOL., Results: Twenty-seven patients (56% females), age 19.4 ± 10.5 years were included; their, FEV1 was 74.6 ± 22.7%, and RV/TLC was (157.3 ± 39.3% predicted). Health perception and lower respiratory symptoms domains of PCD-QOL had the lowest score (median [IQR]: 50 [33.3-64.6] and 57.1 [38.9-72.2], respectively). FOT parameters correlated with several PCD-QOL domains. R5 z-score (indicating total airway resistance) and AX z-score (indicating airway reactance) correlated negatively with physical domain (r = -0.598, p = .001, and r = -0.42, p = .03, respectively); R5 z-score also correlated negatively with hearing domain (r = -0.57, p = .002). R5-20 z-score (indicating small airway resistance) correlated negatively with role domain (r = -0.49, p = .03). SNOT-22 score correlated negatively with several PCD-QOL domains (lower respiratory symptoms r = -0.77, p < .001; physical r = -0.72, p < .001; upper respiratory symptoms r = -0.66, p < .001). No correlations were found between spirometry values, LCI, 6MWT, and PCD-QOL., Conclusions: FOT suggested small airway dysfunction, and correlated negatively with several PCD-QOL domains. Nasal symptoms had strong negative correlations with PCD-QOL. Larger longitudinal studies will further elucidate factors affecting QOL in PCD., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease is unknown. Objectives: To determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2 years. Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1 second (FEV 1 ) ⩽ 40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modeled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV 1 , 30.9% ± 5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex, and FEV 1 revealed percentage predicted peak oxygen uptake ([Formula: see text]o 2peak ) and peak work rate (W peak ) as significant predictors of death/LTX: adjusted hazard ratios per each additional 10% predicted were 0.60 (95% confidence interval, 0.43-0.90; P  = 0.008) and 0.60 (0.48-0.82; P  < 0.001). Tree-structured regression models, including a set of 11 prognostic factors for survival, identified W peak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a W peak  ⩽ 49.2% predicted versus 10.9% for those with a W peak  > 49.2% predicted ( P  < 0.001). Conclusions: CPET provides prognostic information in advanced CF lung disease, and W peak appears to be a promising marker for LTX referral and candidate selection.

Purpose: The kinetics of physiological responses to exercise have traditionally been characterized by estimating exponential equation parameters using iterative best-fit techniques of heart rate (HR) and gas exchange (respiratory rate, oxygen uptake (V̇O 2 ), carbon dioxide output, and ventilation). In this study, we present a novel approach to characterizing the maturation of physiological responses to exercise in children by accounting for response uncertainty and variability., Methods: Thirty-seven early-pubertal (17 females, 20 males) and 44 late-pubertal (25 females, 19 males) participants performed three multiple brief exercise bouts (MBEB). MBEB consisted of ten 2-min bouts of cycle ergometry at constant work rate interspersed by 1-min rest. Exercise intensity was categorized as low, moderate, or high, corresponding to 40%, 60%, and 80% of peak work rate, and performed in random order on 3 separate days. We evaluated sample entropy (SampEn), approximate entropy, detrended fluctuation analysis, and average absolute local variability of HR and gas exchange., Results: SampEn of HR and gas-exchange responses to MBEB was greater in early- compared with late-pubertal participants (e.g., V̇O 2 early-pubertal vs late-pubertal, 1.70 ± 0.023 vs 1.41 ± 0.027; P = 2.97 × 10 -14 ), and decreased as MBEB intensity increased (e.g., 0.37 ± 0.01 HR for low-intensity compared with 0.21 ± 0.014 for high intensity, P = 3.56 × 10 -17 ). Females tended to have higher SampEn than males (e.g., 1.61 ± 0.025 V̇O 2 for females vs 1.46 ± 0.031 for males, P = 1.28 × 10 -4 ). Average absolute local variability was higher in younger participants for both gas exchange and HR (e.g., early-pubertal vs late-pubertal V̇O 2 , 17.48 % ± 0.56% vs 10.24 % ± 0.34%; P = 1.18 × 10 -21 )., Conclusions: The greater entropy in signal response to a known, quantifiable exercise perturbation in the younger children might represent maturation-dependent, enhanced competition among physiological controlling mechanisms that originate at the autonomic, subconscious, and cognitive levels., (Copyright © 2023 by the American College of Sports Medicine.)

Background: The prevalence of nontuberculous mycobacteria (NTM) infections is rising in people with cystic fibrosis (pwCF). NTM infection, especially infection with Mycobacterium abscessus complex (MABC), is commonly associated with severe lung deterioration. The current treatment modalities, including multiple intravenous antibiotics, frequently fail to achieve airway eradication. Although treatment with elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to modulate the lung microbiome, data regarding its role in eradicating NTM in pwCF is lacking. Our aim was to evaluate the impact of ETI on the rate of NTM eradication in pwCF., Methods: This retrospective multicenter cohort study included pwCF from five CF centers in Israel. PwCF aged older than 6 who had at least one positive NTM airway culture in the past two years and were treated with ETI for at least one year were included. The annual NTM and bacterial isolations, pulmonary function tests, and body mass index were analyzed before and after ETI treatment., Results: Fifteen pwCF were included (median age 20.9 years, 73.3% females, 80% pancreatic insufficient). In nine patients (66%) NTM isolations were eradicated following treatment with ETI. Seven of them had MABC. The median time between the first NTM isolation and treatment with ETI was 2.71 years (0.27-10.35 years). Eradication of NTM was associated with improved pulmonary function tests (p<0.05)., Conclusions: For the first time, we report successful eradication of NTM, including MABC, following treatment with ETI in pwCF. Additional studies are needed to assess whether treatment with ETI can result in the long-term eradication of NTM., Competing Interests: Declaration of Competing Interest No conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Background: Myocarditis is one of the presentations of multisystemic inflammatory syndrome in children (MIS-C) following coronavirus disease 2019 (COVID-19). Although the reported short-term prognosis is good, data regarding medium-term functional capacity and limitations are scarce. This study aimed to evaluate exercise capacity as well as possible cardiac and respiratory limitations in children recovered from MIS-C related myocarditis., Methods: Fourteen patients who recovered from MIS-C related myocarditis underwent spirometry and cardiopulmonary exercise testing (CPET), and their results were compared with an age-, sex-, weight- and activity level-matched healthy control group (n = 14)., Results: All participants completed the CPET with peak oxygen uptake (peak [Formula: see text]), and the results were within the normal range (MIS-C 89.3% ± 8.9% and Control 87.9% ± 13.7% predicted [Formula: see text]). Five post-MIS-C patients (35%) had exercise-related cardio-respiratory abnormalities, including oxygen desaturation and oxygen-pulse flattening, compared to none in the control group. The MIS-C group also had lower peak exercise saturation (95.6 ± 3.5 vs. 97.6 ± 1.1) and lower breathing reserve (17.4% ± 7.5% vs. 27.4% ± 14.0% of MVV)., Conclusions: Patients who recovered from MIS-C related myocarditis may present exercise limitations. Functional assessment (e.g., CPET) should be included in routine examinations before allowing a return to physical activity in post-MIS-C myocarditis. Larger, longer term studies assessing functional capacity and focusing on physiological mechanisms are needed., (© 2023. Children's Hospital, Zhejiang University School of Medicine.)

Introduction: Negative pressure pulmonary edema (NPPE) is a potentially life-threatening complication that develops rapidly following acute upper airway obstruction. The condition is rare, dramatic but resolves quickly. Prompt recognition and appropriate supportive treatment may prevent unnecessary investigations and iatrogenic complications., Methods: We describe a spectrum of etiologies and clinical manifestation of pediatric NPPE in our center and review of previous publications., Conclusion: The etiology for the development of NPPE in children has shifted over the years. Although dramatic in presentation, this type of pulmonary edema often resolves quickly with minimal support., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Effective work of breathing and bronchial hygiene requires synergy of inspiratory and expiratory muscles. Inspiratory muscle training (IMT) is a part of pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD). There is some evidence of its efficacy in cystic fibrosis (CF) and, recently, in long COVID-19. We are not aware of studies on IMT in primary ciliary dyskinesia (PCD). Our aim was to assess the effect of IMT on respiratory muscle strength and pulmonary function in PCD and CF patients., Methods: A single center pilot study. Spirometry, lung clearance index (LCI), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were measured at baseline (visit 1), after a month of IMT with ®POWERbreathe (visit 2), and at follow-up (visit 3)., Results: The cohort included 27 patients (19 PCD, 8 CF); mean age 18.4 ± 9.8 years. After a month of IMT, there was a significant increase in MIP and MIP% (6.19-7.44, p = .015; and 81.85%-100.41%, p = .046, respectively), which was sustained at visit 3. Compliance ≥90% led to higher improvement in MIP. In sub-group analysis, improvement in MIP and MIP% remained significant for PCD patients (p = .026 and p = .049, respectively). No significant changes were found in spirometry, MEP or LCI., Conclusions: IMT was well-tolerated and led to improved inspiratory muscle strength in PCD patients. The clinical implication of improved MIP should be further investigated. Larger, long-term studies are needed to evaluate long-term effects of IMT on pulmonary function, respiratory muscle strength, pulmonary exacerbations, and quality of life., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Oral breathing is considered to increase hyper-responsiveness of the airways. Data on the need for nose clip (NC) during exercise challenge test (ECT) in children and adolescents is scarce. Ouraim was to evaluate the role of NC during ECT in children and adolescents., Methods: A prospective, cohort study; children referred for ECT were evaluated on two separate visits, with and without a NC. Demographic, clinical data and measurements of lung functions were recorded. Allergy and asthma control were evaluated by Total Nasal Symptoms Score (TNSS) and Asthma Control Test (ACT) questionnaires., Results: Sixty children and adolescents (mean age 16.7 ± 1.1 years, 38% Female,) performed ECT with NC and 48 (80%) completed visit 2 (ECT without NC), 8.7 ± 7.9 days after visit 1. Following exercise, 29/48 patients (60.4%) with NC had a decline of ≥12% in forced expiratory volume in the first second (FEV 1 ) (positive ECT) compared to only 16/48 (33.3%) positive tests without NC (p = 0.0008). Test result was changed in 14 patients from positive ECT (with NC) to negative ECT (no NC) and in only one patient from negative to positive. The use of NC resulted in greater FEV 1 decline (median 16.3% predicted, IQR 6.0-19.1% predicted vs. median 4.5% predicted, IQR 1.6-18.4% predicted, p = 0.0001), and better FEV 1 increase after bronchodil at or inhalation compared to ECT without NC. Higher TNSS scores did not predict higher probability to positive ECT., Conclusions: The use of NC during ECT increases detection rate of exercise induced bronchoconstriction during ECT in the pediatric population. These findings strengthen the recommendation of nasal blockage during ECT in children and adolescents., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Objectives: We aimed to evaluate the impact of respiratory symptoms and positive viral testing on the risk of serious bacterial infections (SBIs)., Methods: A retrospective study was conducted that included infants (0-60 days) presenting with a fever between 2001 and 2022 at a tertiary hospital in northern Israel. Demographic, clinical, and laboratory parameters were collected, and risk factors for SBIs were analyzed., Results: Data from a total of 3106 infants, including data from blood, urine, and CSF cultures, were obtained in 96.6%, 89%, and 29% of cases, respectively. A fever without respiratory symptoms (fever only) was present in 1312 infants, while 1794 had a fever and respiratory symptoms-427 were positive for a respiratory virus (virus+), 759 tested negative (virus-), and 608 were not tested. The SBI rate was 5.1% vs. 7.5% in the fever-and-respiratory group vs. the fever-only group ( p = 0.004, OR = 0.65 (95% CI = 0.49-0.88)) and 2.8% vs. 7% in the virus+ vs. virus- group ( p = 0.002, OR = 0.385, (95% CI = 0.203-0.728)). The male gender, an age < 1 month, leukocytosis > 15 × 10 9 /L, or a CRP > 2 mg/dL increased the risk of SBIs. Respiratory symptoms or a confirmed viral infection reduced the risk of SBIs in the presence of the above risk factors., Conclusions: Respiratory symptoms and a positive viral test decreased the risk of SBIs. Combining rapid viral testing with clinical variables may identify low-risk infants. Despite the relatively low risk of SBIs in individuals with viral infections, conducting prospective studies remains essential for accurately predicting the occurrence of these potentially life-threatening infections.

Pleuropulmonary blastoma (PPB) is a tumor occurring almost exclusively in infants and young children. This is the most common primary-lung malignancy in childhood. There is age-associated progression through a distinctive sequence of pathologic changes, from a purely multicystic lesion type I to a high-grade sarcoma type II and III. While complete resection is the cornerstone treatment for type I PPB, aggressive chemotherapy with a less favorable prognosis is associated with type II and III. DICER1 germline mutation is positive in 70% of children with PPB. Diagnosis is challenging, as it resembles congenital pulmonary airway malformation (CPAM) in imaging. Although PPB is an extremely rare malignancy, over the past five years we have encountered several children diagnosed with PPB in our medical center. Herein, we present some of these children and discuss diagnostic, ethical, and therapeutic challenges.

The introduction of mutation-specific therapy led to a revolution in cystic fibrosis (CF) care. These advances in CF therapies have changed the disease profile from a severe incurable disease with limited survival to a treatable disease with improved quality of life and survival into adulthood. CF patients are now able to plan their future, including marriage and parenthood. Side by side with the optimism, new issues and concerns are arising, including fertility and preparation for pregnancy, maternal and fetal care during pregnancy, and post-partum care. While cystic fibrosis transmembrane regulator (CFTR) modulators show promising results for improving CF lung disease, data on their safety in pregnancy are still limited. We performed a literature review on pregnancy in CF from the past, with the first described pregnancy in 1960, through the current fascinating changes in the era of CFTR modulators, to ongoing studies and future directions. Current advances in knowledge give hope for improved outcomes of pregnancy, towards the best possible prognosis for the mother and for the baby.

Background: While the positive effect of Trikafta on cystic fibrosis (CF) pulmonary disease is well established, there is limited data about its effect on bone mineral density (BMD), body composition and exercise capacity., Methods: A pilot single center study. BMD and body composition were measured three months after the initiation of Trikafta (study group) and compared to values obtained 2 years earlier. CF patients not treated with Trikafta, for whom BMD was measured 2 years apart, served as controls. Spirometry, lung clearance index (LCI), sweat test, six-min walk test (6MWT) and cardio-pulmonary exercise test (CPET) were performed before and three months after the initiation of Trikafta., Results: Nine study patients, aged 18.6 ± 4.7 years, and nine controls. For the study group, BMI and hip and spine BMD increased significantly (19.4 ± 2.6 to 20.3 ± 2.19 BMI, p = 0.05; 0.73 ± 0.098 to 0.81 ± 0.12 gr/cm 2 hip, p = 0.017; 0.76 ± 0.14 to 0.82 ± 0.14 gr/cm 2 spine, p = 0.025). For the control group, there was no difference in hip or spine BMD. Lean body mass, %fat z-score and fat mass/height 2 z-score increased significantly (34770.23 ± 10521.21 to 37430.16 ± 10330.09gr, p = 0.017; -0.8 ± 0.75 to 0.46 ± 0.58, p = 0.012; and -0.98 ± 0.66 to -0.04 ± 0.51, p = 0.025, respectively). 6MWT improved from 541.1 ± 48.9 to 592.9 ± 54.5 m (p = 0.046). As expected, FEV1%pred increased (p = 0.008) and sweat chloride decreased significantly (p = 0.017). In CPET, VE/VCO 2 improved, indicating better ventilatory efficiency., Conclusions: To the best of our knowledge, this is the first study evaluating the metabolic effects of Trikafta. The results are encouraging and offer hope beyond the well-established effect on pulmonary disease. Larger long-term studies are warranted to unpin the underlying physiological mechanisms., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, there has been a decline in pediatric emergency department visits. Our aim was to assess the pattern of pediatric foreign body aspiration (FBA) during the first year of the COVID-19 pandemic, in comparison to the prior years., Methods: In this retrospective multicenter study, we compared the number of children who presented with FBA during the COVID-19 year (March 1, 2020 to February 28, 2021) to the annual average of the years 2016-2019. We also compared the lockdown periods to the postlockdown periods, and the percentage of missed FBA, proven FBA, and flexible bronchoscopy as the removal procedure., Results: A total of 345 children with FBA from six centers were included, 276 in the pre-COVID-19 years (average 69 per year) and 69 in the COVID-19 year. There was no difference in the prevalence of FBA between the COVID-19 year and any of the prior 4 years. Examining the lockdown effect, the monthly incidence of FBA dropped from a pre-COVID-19 average of 5.75 cases to 5.1 cases during lockdown periods and increased to 6.3 cases in postlockdown periods. No difference in the percentage of missed FB or proven FB was observed. There was a significant rise in the usage of flexible bronchoscopy as the removal procedure (average of 15.4% vs. 30.4%, p = 0.001)., Conclusion: There were fewer cases of pediatric FBA during lockdown periods, compared to post-lockdown periods, presumably related to better parental supervision, with no difference in the prevalence of FBA during the COVID-19 year., (© 2022 Wiley Periodicals LLC.)

Physiological response to physical exercise through analysis of cardiopulmonary measurements has been shown to be predictive of a variety of diseases. Nonetheless, the clinical use of exercise testing remains limited because interpretation of test results requires experience and specialized training. Additionally, until this work no methods have identified which dynamic gas exchange or heart rate responses influence an individual's decision to start or stop physical activity. This research examines the use of advanced machine learning methods to predict completion of a test consisting of multiple exercise bouts by a group of healthy children and adolescents. All participants could complete the ten bouts at low or moderate-intensity work rates, however, when the bout work rates were high-intensity, 50% refused to begin the subsequent exercise bout before all ten bouts had been completed (task failure). We explored machine learning strategies to model the relationship between the physiological time series, the participant's anthropometric variables, and the binary outcome variable indicating whether the participant completed the test. The best performing model, a generalized spectral additive model with functional and scalar covariates, achieved 93.6% classification accuracy and an F1 score of 93.5%. Additionally, functional analysis of variance testing showed that participants in the 'failed' and 'success' groups have significantly different functional means in three signals: heart rate, oxygen uptake rate, and carbon dioxide uptake rate. Overall, these results show the capability of functional data analysis with generalized spectral additive models to identify key differences in the exercise-induced responses of participants in multiple bout exercise testing.

Background: Vascular rings are congenital anomalies of the aortic arch that compress the trachea and esophagus and may require corrective surgery. Data about the long-term effects of vascular rings are scarce. We aimed to evaluate the long-term cardiorespiratory, exercise capacity, and quality of life of vascular ring patients., Methods: A single center prospective study evaluating spirometry, echocardiography, six-minute walk test (6MWT), cardiopulmonary exercise testing (CPET), and quality of life questionnaire (SF36) in patients with a diagnosis of vascular ring, with or without corrective surgery., Results: Twenty-seven patients participated (11.9 ± 6 years, 52% males). The most common diagnosis was double aortic arch (16 patients, 59%). Nineteen patients had corrective surgery (O) and 8 did not (NO). Pulmonary function tests were within normal range in both groups (FEV 1 % predicted O = 87.6 ± 16.5, NO = 83 ± 10.8%). However, 11/27 had abnormal FEV 1 , 5 had abnormal FVC, and 13 (48%) had flattening of the expiratory curve. 6MWD and oxygen uptake were similarly mildly reduced in both groups; (6MWD O = 80.1 ± 10.7% predicted, NO = 74.1 ± 10.9% and oxygen uptake O = 78.5 ± 23.2% predicted, NO = 73.4 ± 14.3%). Peak O 2 pulse (V̇O 2 /HR% predicted) was mildly reduced in the NO group (O = 88.4 ± 17.3%, NO = 75.8 ± 16.2%). Echocardiogram and SF36 scores were normal in all patients., Conclusions: Long-term evaluation of patients born with vascular rings revealed mild pulmonary impairment, reduction in 6MWD, and oxygen uptake. The NO group had also mild reduced peak O 2 pulse. Larger, long-term studies assessing functional parameters in operated and non-operated patients are needed to assess disease/surgery limitation in patients with vascular rings. Clinical trial registration number: NCT04781738., (© 2022 Wiley Periodicals LLC.)

Background and Objectives: Cystic fibrosis (CF)-related diabetes (CFRD) affects 50% of CF adults. Gut microbial imbalance (dysbiosis) aggravates their inflammatory response and contributes to insulin resistance (IR). We hypothesized that probiotics may improve glucose tolerance by correcting dysbiosis., Methods: A single-center prospective pilot study assessing the effect of Vivomixx® probiotic (450 billion/sachet) on clinical status, spirometry, lung clearance index (LCI), and quality of life (QOL) questionnaires; inflammatory parameters (urine and stool metabolomics, blood cytokines); and glucose metabolism (oral glucose tolerance test [OGTT]), continuous glucose monitoring [CGM], and homeostasis model assessment of IR (HOMA-IR) in CF patients., Results: Twenty-three CF patients (six CFRD), mean age 17.7 ± 8.2 years. After 4 months of probiotic administration, urinary cysteine (p = 0.018), lactulose (p = 0.028), arabinose (p = 0.036), mannitol (p = 0.041), and indole 3-lactate (p = 0.046) significantly increased, while 3-methylhistidine (p = 0.046) and N-acetyl glutamine (p = 0.047) decreased. Stool 2-Hydroxyisobutyrate (p = 0.022) and 3-methyl-2-oxovalerate (p = 0.034) decreased. Principal component analysis, based on urine metabolites, found significant partitions between subjects at the end of treatment compared to baseline (p = 0.004). After 2 months of probiotics, the digestive symptoms domain of Cystic Fibrosis Questionnaire-Revised improved (p = 0.007). In the nondiabetic patients, a slight decrease in HOMA-IR, from 2.28 to 1.86, was observed. There was no significant change in spirometry results, LCI, blood cytokines and CGM., Conclusions: Changes in urine and stool metabolic profiles, following the administration of probiotics, may suggest a positive effect on glucose metabolism in CF. Larger long-term studies are needed to confirm our findings. Understanding the interplay between dysbiosis, inflammation, and glucose metabolism may help preventing CFRD., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Late preterm (340−366 weeks gestational age [GA]) infants may have abnormal pulmonary development and possible exercise physiology parameters. We aim to assess the effect of late prematurity on exercise capacity in childhood and to compare it to early preterm (EP) (born < 300 GA), and to term healthy control (TC) (>370 week GA). Methods: Late preterm and early preterm (7−10 years) completed a cardiopulmonary exercise test (CPET) and spirometry and were compared to EP and to TC. Results: Eighty-four children (age 9.6 ± 1.0 years, 48% girls) participated. Twenty-one former LP were compared to 38 EP (15 with Bronchopulmonary dysplasia (BPD) [EP+], 23 without BPD [EP−]) and to 25 TC children. Peak oxygen uptake (peakV̇O2) was statistically lower than in the TC, but within the normal range, and without difference from the EP (LP 90.2 ± 15.1%, TC 112.4 ± 16.9%, p < 0.001; EP+ 97.3 ± 25.5%, EP− 85.4 ± 20.8%, p = 0.016 and p < 0.001, respectively, when compared with TC). Lung function (FEV1) was lower than normal only in the EP+ (75.6 ± 14.9% predicted, compared with 12.5 ± 87.8 in EP−, 87.5 ± 16.9 in LP and 91.0 ± 11.7 in TC). Respiratory and cardiac limitations were similar between all four study groups. Conclusions: This study demonstrated lower exercise capacity (peakV̇O2) in former LP children compared with healthy term children. Exercise capacity in LP was comparable to that of EP, with and without BPD. However, the exercise test parameters, specifically peakV̇O2, were within the normal range, and no significant physiological exercise limitations were found.

Natural patterns of physical activity in youth are characterized by brief periods of exercise of varying intensity interspersed with rest. To better understand systemic physiologic response mechanisms in children and adolescents, we examined five responses [heart rate (HR), respiratory rate (RR), oxygen uptake (V̇O 2 ), carbon dioxide production (V̇CO 2 ), and minute ventilation (V̇E), measured breath-by-breath] to multiple brief exercise bouts (MBEB). Two groups of healthy participants (early pubertal: 17 female, 20 male; late-pubertal: 23 female, 21 male) performed five consecutive 2-min bouts of constant work rate cycle-ergometer exercise interspersed with 1-min of rest during separate sessions of low- or high-intensity (~40% or 80% peak work, respectively). For each 2-min on-transient and 1-min off-transient we calculated the average value of each cardiopulmonary exercise testing (CPET) variable (Y̅). There were significant MBEB changes in 67 of 80 on- and off-transients. Y̅ increased bout-to-bout for all CPET variables, and the magnitude of increase was greater in the high-intensity exercise. We measured the metabolic cost of MBEB, scaled to work performed, for the entire 15 min and found significantly higher V̇O 2 , V̇CO 2 , and V̇E costs in the early-pubertal participants for both low- and high-intensity MBEB. To reduce breath-by-breath variability in estimation of CPET variable kinetics, we time-interpolated (second-by-second), superimposed, and averaged responses. Reasonable estimates of τ (<20% coefficient of variation) were found only for on-transients of HR and V̇O 2 . There was a remarkable reduction in τHR following the first exercise bout in all groups. Natural patterns of physical activity shape cardiorespiratory responses in healthy children and adolescents. Protocols that measure the effect of a previous bout on the kinetics of subsequent bouts may aid in the clinical utility of CPET., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Significance: Growing levels of obesity and metabolic syndrome have driven demand for more advanced forms of body composition assessment. While various techniques exist to measure body composition, devices are typically expensive and not portable, involve radiation [in the case of dual-energy x-ray absorptiometry (DXA)], and are limited to analysis of adiposity while metabolic information from blood supply and oxygenation are not considered., Aim: We evaluate whether diffuse optical spectroscopic imaging (DOSI) can be used to predict site-specific adiposity and percent fat (whole body) while simultaneously providing information about local tissue hemoglobin levels and oxygenation., Approach: DOSI measures of tissue composition in gastrocnemius, quadriceps, abdomen, and biceps, DXA whole-body composition, and ultrasound-derived skin and adipose tissue thickness (SATT) in the quadriceps were obtained from 99 individuals aged 7 to 34 years old., Results: Various DOSI-derived parameters were correlated with SATT and an optical method is proposed for estimating SATT using a newly defined parameter, the optical fat fraction (OFF), which considers all parameters that correlate with SATT. Broadband absorption and scattering spectra from study participants with the thinnest (SATT  ≈  0.25  ±  0.02  cm) and thickest SATT (SATT  ≈  1.55  ±  0.14  cm), representing best estimates for pure in vivo lean and fatty tissue, respectively, are reported. Finally, a trained prediction model is developed which allows DOSI assessment of OFF to predict DXA body-fat percentage, demonstrating that DOSI can be used to quantify body composition., Conclusions: This study shows that DOSI can be used to assess the adiposity of specific tissues or the entire human body, and the OFF parameter is defined for corroboration and further evaluation in future research.

Background: Post mild COVID-19 dyspnea is poorly understood. We assessed physiologic limitations in these patients., Methods: Patients with post mild COVID-19 dyspnea (group A) were compared (pulmonary function tests, 6-min walk test (6MWT), echocardiography and cardiopulmonary exercise test (CPET)) to post moderate/severe COVID-19 (group B) and to CPET and spirometry of patients with unexplained dyspnea (group C)., Results: The study included 36 patients (13 in A, 9 in B and 14 in C). Diffusion capacity was lower in group B compared to group A (64 ± 8 vs. 85 ± 9% predicted, p = 0.014). 6MWT was normal and similar in both patient groups. Oxygen uptake was higher in group A compared to groups B and C (108 ± 14 vs. 92 ± 13 and 91 ± 23% predicted, p = 0.013, 0.03, respectively). O 2 pulse was normal in all three groups but significantly higher in the mild group compared to the control group. Breathing reserve was low/borderline in 2/13 patients in the mild group, 2/9 in the moderate/severe group and 3/14 in the control group (NS)., Conclusions: Patients with post mild COVID-19 dyspnea had normal CPET, similar to patients with unexplained dyspnea. Other mechanisms should be investigated and the added value of CPET to patients with post mild COVID-19 dyspnea is questionable.

Background: Patients with primary ciliary dyskinesia (PCD) have chronic morbidities affecting their quality of life (QOL). Health-related QOL (HRQOL) has been recognized as an important tool for assessing the burden of PCD on patients and their families. A PCD-specific HRQOL questionnaire (QOL-PCD) was developed and validated for the English-speaking populations. Still, it has not yet been translated into Hebrew or adapted for Israeli PCD patients., Methods: This describes our translation of the original English version of QOL-PCD into a Hebrew version. The process involved forward translation by independent translators, construction of a consensus version, back-translation into the original English version, analysis by the expert committee, and a pretest. The pretest was administered to 20 participants with PCD (the patients and the parents of minor patients) to assess the feasibility and practicality of the tool. Scale and item indices (scale-level content validity index [S-CVI] and item-level content validity index [I-CVI]) were calculated for content validity., Results: All study participants understood the final Hebrew version that the expert committee had approved with no difficulty. The instrument had satisfactory (>0.80) content validity, with S-CVI indexes of 0.99 for the adult version, 0.86 for the parental version, 0.95 for the adolescent version, and 1.00 for the child version., Conclusion: The English version of a QOL-PCD was translated into Hebrew and adapted in Israel. This translation is a valid instrument to assess HRQOL in Hebrew-speaking patients with PCD and their family members. It may be helpful for PCD patient management and research in Israel., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Purpose: The electronic health record, data science advances, and dynamic environmental and infectious threats to child health highlight the need for harmonized and interoperable approaches to pediatric cardiopulmonary exercise testing (CPET). Accordingly, we developed a terminology harmonization in exercise medicine and exercise science domain analysis model (THEMES DAM) to structure CPET data elements., Methods: THEMES DAM identified 114 data elements, including participant information, calibration, equipment, protocols, laboratory personnel, encouragement strategies, and analysis procedures. We used the THEMES DAM, vetted by the international data standards organization HL7, to construct a current-state survey of pediatric CPET centers in the United States. Forty-eight of 101 centers responded to a questionnaire covering seven major topic areas (38 items)., Results: Centers predominantly performed between 100 and 500 tests annually. Cardiac disease represented 55% of referrals. Almost all centers calibrated gas concentrations and flow daily, but 42% never calibrated their treadmill or cycle ergometers. All centers measured V̇O2peakbut calculated differently. Centers used a variety of protocols (e.g., for treadmill: 61%, Bruce; 43%, modified Bruce; 59%, other); 44% calculated CPET slopes from submaximal portions of CPET (e.g., V̇O2-HR). All centers verbally encouraged participants, but only 40% used a standardized approach. The interpretation of CPET was done by physicians (60%), exercise physiologists (25%), exercise technicians (10%), nurses (1%), or others (4%). Ninety-one percent would agree to collaborate in multicenter research, 89% to establish dynamic reference values, and 83% to better interpret CPET., Conclusions: The survey data and the implementation of THEMES DAM could accelerate interoperability across multiple centers. This would facilitate a nimble approach to create pediatric reference values responsive to the constantly changing health environment and stimulate novel approaches to CPET research and clinical application., (Copyright © 2022 by the American College of Sports Medicine.)

Introduction: Following the opening of lockdown and relaxation of public health restrictions, an unusual surge of respiratory illness occurred during the spring/summer (Q2) 2021 season. We aimed to characterize this surge compared to previous years., Methods: Children discharged from a single tertiary hospital for respiratory illness or selected noncommunicable diseases (NCDs) between 2015 and 2021 were included, and hospitalization rates were compared. To evaluate whether the current respiratory surge resembles a typical winter, characteristics of the second quarter (Q2, April-June) of 2021 were compared to parallel seasons and to autumn/winter (Q4, October-December) of the previous years., Results: Respiratory illness showed a seasonal peak, while the pattern of NCD was consistent throughout the study period. Respiratory illnesses showed a delayed surge in Q2 2021 (389 patients), with a missing seasonal peak in Q2 and Q4 2020 (135 and 119 patients, respectively). There were more cases of croup in Q2 2021 compared to Q2 and Q4 2015-2019 (26.2 vs. 12.5% and 15.8%, p < 0.001), fewer cases of pneumonia (5.9 vs. 15.9% and 11.7%, p < 0.001), lower admission rates (22.4 vs. 36.3% and 31.5%, p < 0.001), and fewer hypoxemia during hospitalization (6.3 vs. 11.7% and 10%, p < 0.001). Additionally, lower use of antibiotics (6.2 vs. 12.3% and 10.3%, p = 0.001 and 0.012, respectively) and higher use of steroids (33.7 vs. 24.8% and 28.3%, p < 0.001 and 0.034, respectively)., Conclusions: The postponed increase in respiratory morbidity after lockdown had unique characteristics, with upper respiratory illness predominating and fewer hospitalizations. Follow-up is needed to assess the altered epidemiological patterns of respiratory diseases in the post-COVID era., (© 2021 Wiley Periodicals LLC.)

Background: Specialization in medical professions is considered a challenging and intensive period due to the number and sequence of duty hours. Considering the effect of duty hours on residents, both physically and mentally, several models have been created over the years to address this complexity. The two main model schools aim to decrease the duty hour length and night shift (i.e., night float, NF) frequency. In recent years, duty hours have become a source of disagreement and frustration among the medical community, both residents and attendings. A possible change in the duty hour structure may affect residents in terms of several parameters, such as patient safety, the well-being of the physician and the degree of training of the resident., Purpose: (1) To investigate medical residents' perspectives on their duty hours utilizing online questionnaires on their effect on the work environment and (2) to assess residents' preferences in relation to the suggested shortened shift and NF models., Methods: Questionnaires were emailed to all residents (main residents and fellows) at an Israeli tertiary medical center between March 2020 and April 2020. Questions were scored from 1 (disagree) to 5 (fully agree)., Results: Two hundred and sixty residents (227 main residents, 43 fellows) participated in the study (40% female). The score for the degree of balance between work and personal life was low (0.9±1.99). The shortened shift model was perceived by the residents as more compatible with a balanced lifestyle than the NF model (3.77 ± 1.20 and 3.14 ± 1.26, respectively, P < 0.0001). Neither model was considered to risk impairing professional training (2.33 ± 1.45 and 2.47 ± 1.25, respectively, P = 0.12). Overall, 74% of the residents were not willing to lower their income if the decision were made to change models, and 56% were not willing to increase the number of shifts., Conclusions: There is agreement among residents that shortening shift hours to 16 h would have a positive effect on the balance between personal life and work. In the eyes of residents, the change would not impair their training during residency., (© 2022. The Author(s).)

Purpose: Relvar® (fluticasone furoate [FF]/vilanterol [VI]) is a once-daily inhaler with bronchodilator effect lasting 24 h. Our aim was to investigate the short- and long-term effects of FF/VI on exercise-induced asthma (EIA) in adolescents., Methods: Ninety-three adolescent asthmatics aged 12-18 years were referred for evaluation of EIA. Following a positive exercise challenge test (ECT), 22/44 were allocated to a single administration of salbutamol (400 μg) and 22/44 to FF/VI (92/22 μg) in a double-blind method. Thirty-five subjects were reassessed by repeat ECT 30-60 days of FF/VI., Results: Median FEV 1 change post-ECT at baseline was -22.8% predicted (interquartile range [IQR] -26.1 and -18.0) for salbutamol and -21.0 (IQR -30.7 and -16.8) for FF/VI. Following bronchodilator, FEV 1 improved similarly in both groups. Repeat ECT following 30-60 days of FF/VI resulted in negative ECT in 33/35 subjects; the median decrease in FEV 1 of these 35 subjects was 22.6% predicted (IQR 29-18) before, and 4.6% predicted (IQR 8.7-2.5) after 30-60 days of FF/VI treatment (p < 0.0001)., Conclusions: FF/VI is effective in reversing EIA after 15 min in adolescents and in protecting EIA after 30-60 days in adolescents. Larger studies are needed to assess the effect of FF/VI on EIA., (© 2021 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Background: Enzyme replacement therapy (ERT) with alglucosidase alfa improves the prospect of patients with infantile-onset Pompe disease (IOPD). However, a progressive decline has been reported. Objective quantification of the response to ERT when assessing newer strategies is warranted., Methods: This combined retrospective-prospective study assessed the acute and long-term effects of ERT on exercise in IOPD patients. Evaluation included cardiopulmonary exercise testing (CPET), 6-min walking test (6MWT), spirometry, motor function test (GMFM-88) and enzyme blood levels., Results: Thirty-four CPETs (17 pre- and 17 two days-post ERT) over variable follow-up periods were performed in four patients. Two days following ERT, blood enzyme levels increased (median, 1.22 and 10.15 μmol/L/h ( p = 0.003)). However, FEV1, FVC and GMFM-88, the median 6MWD and the peak VO 2 were unchanged. Long-term evaluations showed stabilization in young patients but progressive deterioration in adolescents. Clinical deterioration was associated with more pronounced deterioration in peak VO 2 followed in the decreasing order by 6MWD, FVC and GMFM-88., Conclusions: The peak VO 2 and 6MWD might serve as more sensitive markers to assess clinical deterioration. More studies are needed to clarify the sensitivity of the peak VO 2 and 6MWT for quantification of individualized response. This may be important when assessing newer strategies and formulations in IOPD.

Background: Infant pulmonary function tests (iPFTs) in subjects with neuroendocrine cell hyperplasia of infancy (NEHI) have demonstrated substantial expiratory airflow obstruction and air trapping., Research Question: Can indices from iPFTs be used in the diagnosis of NEHI?, Study Design and Methods: This is an observational case-control study evaluating iPFT results from a registry of patients assessed at the Hadassah Hebrew University Medical Center between 2008 and 2018. iPFTs results in infants with NEHI were compared to two disease control infant groups (infants evaluated for recurrent wheezing and infants evaluated due to prematurity) and a spirometry control group of infants with normal expiratory airflow, using the Kruskal-Wallis test. Receiver operating characteristic (ROC) curves were used to assess the diagnostic accuracy of iPFT indices., Results: We evaluated iPFT data in 481 infants (15, NEHI; 292, wheezing; 128, premature; and 46, spirometry control group). Infants with NEHI had significantly increased trapped air volumes (median functional residual capacity measured with infant whole-body plethysmography [FRC pleth ] was 199% predicted; median ratio of residual volume to total lung capacity was 59% predicted) when compared with results in all evaluated groups of infants (P < .001), including multiple pairwise comparisons. Airflow limitation was demonstrated in infants with NEHI when compared with the infants in the spirometry control group but was similar to the two disease control groups. FRC pleth had the best discriminatory ability for NEHI diagnosis, with an FRC pleth  ≥ 150% predicted demonstrating a ROC of 0.91 (95% CI, 0.82-1.00), sensitivity of 86.7% (95% CI, 59.5%-98.3%), and specificity of 95.5% (95% CI, 93.2%-97.3%)., Interpretation: Findings on iPFTs of markedly increased air trapping, out of proportion to the degree of airflow limitation, are characteristic of infants with NEHI. iPFT results demonstrating an FRC pleth  ≥ 150% predicted are highly specific for NEHI and may aid in early diagnosis. Further research is required to confirm these findings in a prospective cohort and to understand the pathophysiologic explanation for these findings., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Pulmonary nodules present a diagnostic challenge when they appear as atypical metastases in pediatric oncology patients. Chest computed tomography (CT) is the primary imaging modality for assessing lung nodules. In pediatric populations, Wilms tumor and osteosarcoma are the cancers most likely to produce pulmonary metastasis, both typical and atypical. This pictorial essay provides a thorough description of the specific radiologic features of atypical pediatric pulmonary metastases, and their pathogenesis and differential diagnosis. We also address diagnostic approaches to incidental lung nodules in healthy children found in the literature. Our aim is to help radiologists identify atypical lung metastases on CT, ensuring that children receive prompt, and potentially lifesaving, treatment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Introduction: Community acquired pneumonia (CAP) is a leading cause of morbidity in children, despite advances in health care and anti-pneumococcal vaccine. Complicated pneumonia accounts for a significant burden with prolonged hospitalization. Finding risk factors for complicated pneumonia may help in tailoring management. We aimed to identify risk factors for developing complicated pneumonia and need for intervention., Methods: A retrospective single tertiary center study. Children admitted with a diagnosis of CAP and/or complicated pneumonia (parapneumonic effusion, empyema, necrotizing pneumonia, and lung abscess) on January 2001-March 2020 were included. Demographic, clinical, and laboratory parameters were collected using MDclone, a data acquisition tool. Risk factors for complicated pneumonia (on admission or during hospitalization) and risk for intervention were analyzed., Results: A total of 6778 children with pneumonia were included; 323 arrived at the Emergency Department with complicated pneumonia while 232 developed a complication during hospitalization. Risk factors for complicated pneumonia (on admission or during hospitalization) were Arab ethnicity, cardiac disease, increased age, and CRP and low O 2 Sat (OR = 2.236 p < .001, OR = 4.376 p < .001, OR = 1.131 p < .001, OR = 1.065 p < .001 and OR = 0.959 p = .029, respectively). O 2 Sat was lower, while fever and CRP were higher in patients with complicated pneumonia requiring intervention., Conclusions: Identifying children at risk for complicated pneumonia may help in decision-making in the Emergency Department and during hospitalization. The increased risk of the Arab population for complicated pneumonia requires further understanding. Addressing the underlying socioeconomic and ethnic health inequities may help to decrease the disease burden in this population., (© 2021 Wiley Periodicals LLC.)

A 16-year-old adolescent presented with dry cough, fever, weight loss, night sweats, exercise intolerance, and eosinophilia. Computed tomography showed consolidations with "reverse butterfly" pattern. He responded well to corticosteroids but had frequent relapses. He became steroid dependent and developed steroid related morbidity. Benralizumab was prescribed with complete resolution of eosinophilia and lung infiltrates with no adverse effect., (© 2021 Wiley Periodicals LLC.)

Assessing disease severity in patients with cystic fibrosis (CF) is essential when directing therapies. Serum immunoglobulin G (IgG) levels increase with disease severity. Lung clearance index (LCI) is recognized as an outcome measure for CF clinical trials. Our aim was to evaluate the correlations between IgG and disease severity markers. This was a single-center retrospective study, evaluating association between IgG and markers of severity in CF patients (including clinical characteristics, lung spirometry, LCI, clinical scores and computed tomography (CT) scores) during stable conditions. There were 69 patients, age 20.5 ± 11.6 years. Nineteen (27.5%) patients had elevated IgG. IgG correlated positively with LCI (r = 0.342, p = 0.005). IgG was higher in pancreatic insufficient (PI) and patients with liver disease (1504.3 ± 625.5 vs. 1229 ± 276.1 mg/dL in PI vs. PS, p = 0.023, and 1702.6 ± 720.3 vs. 1256.2 ± 345.5 mg/dL with vs. without liver disease, p = 0.001, respectively). IgG also correlated positively with CRP, CT score, and days with antibiotics in the previous year (r = 0.38, p = 0.003; r = 0.435, p = 0.001; and r = 0.361, p = 0.002, respectively), and negatively with FEV1% and SK score (r = -0.527, p < 0.001 and r = -0.613, p < 0.001, respectively). IgG correlated with clinical parameters, pulmonary functions, and imaging. However, this is still an auxiliary test, complementing other tests, including lung function and imaging tests. Larger multi-center longitudinal studies are warranted.

Objectives: To evaluate the ethnic distribution of Israeli patients with the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA)., Study Design: The medical records of patients with PFAPA attending 2 pediatric tertiary medical centers in Israel from March 2014 to March 2019 were retrospectively reviewed. Patients with concomitant familial Mediterranean fever were excluded. Ethnicity was categorized as Mediterranean, non-Mediterranean, and multiethnic. Findings were compared with patients with asthma under treatment at the same medical centers during the same period., Results: The cohort included 303 patients with PFAPA and 475 with asthma. Among the patients with PFAPA, 178 (58.7%) were of Mediterranean descent (Sephardic Jews or Israeli Arabs), 96 (33.0%) were multiethnic, and 17 (5.8%) were of non-Mediterranean descent (all Ashkenazi Jews). Patients with PFAPA had a significantly higher likelihood of being of Mediterranean descent than the patients with asthma (58.7% vs 35.8%; P < .0001). The Mediterranean PFAPA subgroup had a significantly earlier disease onset than the non-Mediterranean subgroup (2.75 ± 1.7 vs 3.78 ± 1.9 years, P < .04) and were younger at disease diagnosis (4.77 ± 2.3 vs 6.27 ± 2.9 years, P < .04)., Conclusions: PFAPA was significantly more common in patients of Mediterranean than non-Mediterranean descent. Further studies are needed to determine the genetic background of these findings., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Objectives: Multiple factors affect bone mineral density (BMD) in cystic fibrosis (CF). Our aim was to perform comprehensive analyses of parameters potentially contributing to BMD., Methods: A prospective single-center study assessing BMD, and correlations with multiple parameters including pancreatic status, lung functions, 6-minute walk test (6MWT), clinical score (modified Shwachman-Kulczycki [SK] score), vitamin D, nutritional intake, hand grip strength (HGS), habitual physical activity (smart watches), and quality of life (SF-36 questionnaire)., Results: Forty CF patients, mean age 18.3 ± 8.1 years, forced expiratory volume in 1 second 74.7% ± 17.9% predicted. Fifteen (37.5%) and 11 (27.5%) had osteopenia and osteoporosis, respectively. BMD was similar in pancreatic sufficient (pancreatic sufficient [PS], n = 15) and insufficient (pancreatic insufficient [PI], n = 25); median hip z score -1.5 ((-2.7)-(+0.2)) vs -1.5 ((-3.5)-(+0.7)), P = .79; spine -0.8 ((-2.2)-(+2)) vs -1.2 ((-4.4)-(+1.5)), P = .39 in PS vs PI, respectively. BMD correlated with HGS (r = .72, P < .001 hip; r = .52, P = .001 spine) and fat-free mass index (r = .81, P < .001 hip; r = .63, P < .001 spine). BMD z score correlated weakly with SK score and moderately with SF-36 general health. Data from smart watches, nutrition questionnaires, and 6MWT did not correlate with BMD. In a multivariate model, age and SK score predicted spine z score BMD., Conclusions: A substantial number of CF patients have low BMD. Similar rates in PS and PI suggest that other factors, such as disease severity, may contribute to low BMD. SK and age, which can easily be obtained even with limited resources, were the best predictors of low BMD. Further larger multicenter studies are warranted to evaluate the contribution of multifactorial etiologies to low BMD in CF., (© 2020 Wiley Periodicals LLC.)

Introduction: α Mannosidosis is an extremely rare, progressive, and complex lysosomal storage disease, characterized by mental retardation, hearing impairment, coarse facial features, skeletal abnormalities, and pulmonary involvement. While bone marrow transplantation has been the only therapeutic option to date, nowadays new treatment options are being explored, which may affect pulmonary and exercise capacity., Aim and Methods: To assess cardiopulmonary involvement in patients with α mannosidosis by pulmonary function tests, cardiopulmonary exercise testing, and low irradiation chest computed tomography (CT)., Results: Five patients aged 11 to 28 years were followed in our Respiratory-Metabolic Clinic. All five had pulmonary symptoms and received inhaled therapy. Three patients underwent bone marrow transplantation. Parenchymal lung disease was evident in 3/5 chest CT tests. Pulmonary function tests were abnormal in all patients and showed obstructive/restrictive impairment with air trapping. All five patients showed reduced peak oxygen uptake (median 23.1; range 20.4-32.2 mL/minute/kg, median %predicted 62; range %predicted 59-79)., Conclusions: Pulmonary involvement is a known complication in this rare disease. Comprehensive cardiopulmonary evaluation is feasible among these patients and may help in assessing disease progression and response to new treatment modalities., (© 2020 Wiley Periodicals LLC.)

Background: Insulin promotes glucose consumption as the main cardiac energy source, while increasing myocardial efficiency. The short-term effects of insulin on cardiac function and its potential curative role in an acute diabetological cardiology setting remain unknown. Our study evaluated the role of acute insulin administration in the diabetic heart, its corresponding effective blood insulin level, and the time-course applicability of insulin treatment in a routine clinical setting., Methods: We evaluated a case series of six male (48.1 ± 4.9 y/o) patients with controlled diabetes (HbA1c of 6.6 ± 0.3%) and disease duration of 14.4 ± 6.7 yr. Each subject was evaluated for glucose homeostasis, as well as hemodynamic and echocardiographic (systolic and diastolic) parameters at three points: baseline followed by two successive insulin loads in euglycemic hyperinsulinemic clamp study. Results were analysed using Student's t -test., Results: The first insulin load led to a physiologic blood insulin level of 145 ± 36  μ U/ml, and both systolic (7 mmHg) blood pressure and diastolic (4 mmHg) blood pressure decreased significantly. Left ventricular fractional shortening (LVFS) increased significantly by 11.8%. Diastolic function parameters of mitral annulus movement of the A' wave increased relative to baseline by 20.0% (27.8% under the second insulin load), A' medial increased relative to baseline by 30%, and A' lateral increased relative to baseline by 17%, displayed by tissue Doppler imaging., Conclusions: Insulin acutely affected the diabetic heart at a physiologic level within a 2 h time course. Insulin mainly increased left ventricular systolic function and, to a second degree, improved left ventricular diastolic functions and atrial systole in diabetic subjects. These results may facilitate the development of insulin-based acute treatment in diabetic patients with cardiac morbidity. This trial is registered with NCT02962921., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Deeb Daoud Naccache et al.)

Objectives: Reports suggest that children with type 1 diabetes (T1D) perform less than the recommended daily activity and are less active than their non-diabetic peers. We aimed to: (a) Identify barriers and sources of support for exercise performance in pediatric T1D. (b) Identify strengths and limitations in the exercise-directed education provided by our diabetes team., Methods: Patients with T1D 5 to 20 years of age were recruited while attending a routine clinic visit. Participants completed a set of questionnaires assessing demographics, health data, barriers, and sources of support for exercise performance and diabetes related exercise education. The clinics' medical staff filled-out a questionnaire assessing the exercise-directed education provided in clinic., Results: Ninety-six subjects were included in this study, mean age 13.7 ± 3.8 years. Median weekly reported exercise time was 3.5 hours. The two most prevalent barriers were fear of hypoglycemia and low fitness, reported by 76% and 51%, respectively. Mean family and social support scores were 4.1 ± 0.7 and 3.3 ± 1.1, respectively (1-5 scale); the latter correlated with the amount of activity performed (cc = 0.360; P < .001). The majority of participants (97%) reported receiving guidance for physical activity, to their satisfaction. Yet, knowledge and implementation were suboptimal. All staff members reported conducting routine exercise-directed teaching, with variations in frequency and content., Conclusions: Our findings suggest that in order to increase the amount of safely performed exercise in pediatric patients with T1D, fear of hypoglycemia must be addressed. Further efforts should focus on: (a) encouraging active family and social involvement (b) standardization of education., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)