In conclusion, our data suggest that subjects with genotype 5T;TG12/VVCC likely have a very low risk of progressing to CF, as compared to those with F508del/5T;TG12. 4 This observation could lead to differentiate follow up in presence of at least one 5T;TG12. Knowing these data is crucial to offer a useful counseling for CRMS/CFSPID infants and for non‐CF adults with CBAVD alone. Anyway further data are needed to evaluate the outcomes after a longer follow up.

Introduction: Assessment of and intervention for sleep-disordered breathing and malnutrition are related to respiratory management for preventing recurrent respiratory tract infections (RRTIs) and acute respiratory failure (ARF) in children with spinal muscular atrophy (SMA). However, the specific standard has not been clarified. Purpose: The study aimed to obtain the risk factors and the predictive index for RRTIs and/or ARF in children with SMA. Methods: In this retrospective study, the differences in clinical characteristics in patients with or without RRTIs and ARF were compared, and binary logistic regression analysis was carried out. The best cutoff points of the positive predictive index were obtained. Results: Type 1 (OR = 4.12, 95% CI 1.30-13.07, P =.016) and apnea hypopnea index (AHI) (OR = 1.14, 95% CI 1.05-1.24, P =.001) were risk factors, while body mass index z score (BMIz) (OR = 0.68, 95% CI 0.49-0.94, P =.018) and mean pulse oxygen saturation (MSpO 2) (OR = 0.67, 95% CI 0.50-0.91, P =.010) were protective factors. The sensitivity and specificity of the standard of MSpO 2 < 96% and AHI > 10 events/h or BMIz < -1 with the occurrence of RRTIs and/or ARF were 0.513 and 0.957, respectively. Conclusion: SMA Type 1, BMIz, AHI and MSpO 2 should be used to estimate the risk for RRTI or ARF in children with SMA. MSpO 2 < 96%, and AHI > 10 events/h or BMIz < -1 should be used as the intervention standard.

Objective: To evaluate the functional capacity, pulmonary function and quality of life of children and adolescents with sickle cell anemia (SCA) and to test the reproducibility of functional capacity tests in this population. Method: Cross-sectional study with  volunteers with SCA genotype Hb-SS (SCAG), aged 6 to 18 years matched in age and  gender to the control group (CG). Spirometry, 5-repetition sit-to-stand test (5STS-test),  modified shuttle walk test (MSWT), and Pediatric Quality of Life Questionnaire (PedsQL) were performed. The reproducibility of 5STS-test and MSWT was evaluated:   Results: 48 volunteers of SCAG and 48 of CG were evaluated. Pulmonary function of SCAG (FVC: 92 ± 15% pred.; FEV 1 /FVC: 84 ± 8% pred.) was worse than the CG (104 ± 15% pred.; FEV 1 /FVC: 90 ± 6% pred.) p < 0.05. SCAG had worse functional capacity registered by distance walked: 576m (515-672m) and 5STS-test: 8 seconds (7.4-8.9seconds) compared to the CG who showed distance walked: 1010m (887- 1219m) and 5STS-test: 7 seconds (7.0-8.1seconds), p < 0.001. SCAG had worse quality compared to CG, p < 0.05. The reproducibility was good of MSWT (ICC 0.99 (0.98-0.99 IC-95%)) and 5STS-test (ICC 0.80 (0.69 – 0.88), p < 0.001 . Conclusion: Children and adolescents with sickle cell anemia showed worse capacity to walk or run, and to perform sit-to-stand test. Additionally, they have poor quality of life when compared with their control peers. The MSWT and 5STS-test showed reproducible to be applied in pediatric individual with SCA.

Rationale: As a result of the SARS-CoV-2 pandemic, all pediatric pulmonary fellowship programs conducted virtual interviews for the first time in the Fall of 2020. This study aimed to understand the accuracy of virtual-interview derived-impressions of fellowship programs, as well as applicant preference for future fellowship interview cycles. Methods: A group of pediatric pulmonary fellows and Program Directors designed a REDCap survey. The survey was distributed to all first-year pediatric pulmonary fellows who participated in the 2020-2021 virtual interview season. Results: 23/52 (44%) of first-year pediatric pulmonary fellows completed the survey. 96% were able to form general impressions about fellowship programs during their virtual interviews. 96% reported that generally their fellowship experience matched their virtual-interview derived-impressions. 17 of 19 factors applicants use to rank programs had no statistically significant change (p > 0.05) in impression from virtual interview to fellowship experience. The two factors with a statistically significant (p < 0.05) change in impression were patient care related – volume of ‘bread and butter’ pediatric pulmonary patients and volume of tertiary care pediatric pulmonary patients. 87% prefer some form of in-person interview option in future application cycles. A tiered interview format in which applicants are first invited to a virtual interview day followed by an optional in-person second look day was the most popular preference for future interview cycles (48%). Conclusions: Virtual interviews may provide accurate representations of pediatric pulmonary fellowship programs and applicants prefer some type of in-person interview option in future application cycles.

Introduction: Acute bronchiolitis (AB) is the main cause of hospitalization in children under two years of age, with a regular seasonality, mostly due to the respiratory syncytial virus (RSV).Objectives: To describe the epidemiology of bronchiolitis hospitalizations in our centre in the last twelve years, and analyse the changes in clinical characteristics, microbiology, and adverse outcomes during the SARS-CoV2 pandemic.Methods: Observational study including patients admitted for bronchiolitis between April 2010 and December 2021 in a Spanish tertiary paediatric hospital. Relevant demographic, clinical, microbiological, and adverse outcome variables were collected in an anonymized database. The pandemic period (April 2020 to December 2021) was compared to 2010-2015 seasons using appropriate statistical tests.Results: There were 2138 bronchiolitis admissions, with a mean of 195.6 per year between 2010-2019 and a 2–4-month peak between November and March. In the expected season of 2020, there was a 94.4% reduction of bronchiolitis hospitalizations, with only eleven cases admitted in the first year of the pandemic. Bronchiolitis cases increased from the summer of 2021 during a six-month long peak, reaching a total of 171 cases. Length of stay was significantly shorter during the pandemic, but no differences were found in clinical and microbiological characteristics or other adverse outcomes.Conclusions: The SARS-CoV2 pandemic has modified the seasonality of bronchiolitis hospitalizations, with a dramatic decrease in cases during the expected season of 2020-2021, and an extemporaneous summer-autumn peak in 2021 with longer duration but similar patient characteristics and risk factors.

This case illustrates another promising example of the recent advances within pediatric interventional bronchoscopy. As innovative medical therapies continue to make their way into the pediatric realm (e.g. a 1.1-mm flexible cryoprobe has been recently developed by Erbe), opportunities for novel approaches and techniques will continue to present themselves.

Objective: This systematic review aimed to systematize different designs of exercise-based pulmonary rehabilitation (PR) for children with asthma and explore which designs are optimal. Methods: PubMed, EMBASE, Cochrane Library, Web of Science Core Collection and MEDLINE were searched up until April 01, 2021, which was conducted for any relevant randomized controlled trials (RCTs) of exercise-based PR in childhood asthma. Language is limited to English. Network meta-analyses and standard meta-analyses were performed using STATA (version 16.0), quality analyses were performed using RevMan (version 5.3). Results: A total of 24 RCTs involving 1031 patients were included. 14 studies were endurance training, which was the most commonly used form of exercise, and 7 studies rehabilitation sites were conducted in hospitals. A network meta-analysis showed that compared with other forms of exercise, interval training significantly improved the PAQLQ (Pediatric Asthma Quality of Life Questionnaire), including activity scores [MD=3.02, 95% CI (1.74,4.30)], symptom scores [MD=2.68, 95% CI (2.04,3.32)], emotional scores [MD=2.47, 95% CI (0.91,4.03)], and total scores [MD=2.68, 95% CI (1.79,3.57)]. Interval training [MD=188.97, 95% CI (-59.27, 437.21)] also had a more significant effect on the 6MWT (6-minute walk test). No adverse events were found in this study. Exercise training had no significant effect on FEV 1(the forced expiratory volume at 1s to predicted value ratio) [WMD=0.59, 95% CI (-2.00, 3.19)], however, the combined of endurance training and respiratory training was found to significantly improve both FVC (the forced vital capacity to predicted value ratio) [MD=5.37, 95% CI (0.07,10.67)] and FEF25-75% (the forced expiratory flow between 25% and 75% of vital capacity ratio) [WMD=11.31, 95% CI (2.13, 20.48)]. Conclusions: Exercise-based PR is a safe and effective for childhood asthma. Interval training may be a core component of improving quality of life and exercise capacity in childhood asthma, the combination of respiratory training and endurance training has significant effects on lung function.This result should be viewed with caution, and high-quality RCTs are still needed to confirm its clinical efficacy,

Background: Observational studies suggest that asthma/wheezing improve after adenotonsillectomy (AT). However, there is a paucity of RCT specifically studying the effects of AT in asthma/wheezing. Therefore, we conducted a post-hoc analysis of the Childhood Adenotonsillectomy Trial, the largest RCT of AT in children with obstructive sleep apnea (OSA) to test the hypothesis that AT would result in fewer wheezing episodes. Methods: In the CHAT study, 464 children with OSA, aged 5 to 9 years, were randomized to early AT (n=226) or watchful waiting with supportive care (WWSC) (n= 227). For this post-hoc analysis children were categorized as having “any wheezing” vs. “no wheezing” at baseline and at 7 months of follow-up. A multivariate analysis was conducted to evaluate the association between “any wheezing” at follow-up and treatment group after controlling for several potential confounders. Results: Children in the “any wheezing” group were predominantly black, had more allergic rhinitis, eczema, second-hand smoke exposure, more siblings and siblings with asthma, lower maternal education and family income than those in the “no wheezing group”. At baseline, wheezing characteristics were similar between AT and WWSC arms. At follow-up (at 7 months of the intervention) those in the AT arm had significatively less wheezing than those in the WWSC (22.4% vs. 43.8%, p=0.00001). However, the multivariate analysis of “any wheezing” vs. “no wheezing” at follow-up showed that the treatment arm was not associated with wheezing. Conclusion: This study demonstrated that AT has not effect on wheezing at 7 months of follow-up.

This study aimed to investigate epidemiological, clinical, and laboratory features of children with COVID-19 to identify predictors for pulmonary involvement. We conducted a retrospective, single-center study of pediatric COVID-19 at a tertiary care hospital in Turkey between December 2020 and June 2021. A total of 126 children (70 males, 55.6%) were examined during the study period. Their mean age was 74.73 ± 81.11 months (range, 1–216 months). The most frequent COVID-19 symptoms were fever (65.9%), cough (52.4%), and shortness of breath (18.3%). Ten patients required noninvasive mechanical ventilation. Sixty-nine patients (54.8%) had pneumonia. Longer duration of fever and the presence of cough were significantly associated with pulmonary involvement. In children with pneumonia, the C-reactive protein (CRP), procalcitonin levels, erythrocyte sedimentation rate (ESR), and viral load were significantly higher and lymphocyte and thrombocyte counts were significantly lower than in children without pneumonia. The cutoff viral load, CRP, and procalcitonin values for predicting pulmonary involvement were 26.5 cycle threshold (Ct; 95% confidence interval [CI], 0.54–0.74; sensitivity, 0.65; specificity, 0.56; area under curve [AUC]: 0.647, p = 0.005), 7.85 mg/L (95% CI, 0.56–0.75; sensitivity, 0.66; specificity, 0.64; AUC = 0.656; p = 0.003) and 0.105 ng/mL (95% CI, 0.52–0.72; sensitivity, 0.55; specificity, 0.58; AUC = 0.626; p = 0.02), respectively. High CRP, procalcitonin levels, ESR, and viral load and low lymphocyte and thrombocyte counts can predict pulmonary involvement in children with COVID-19, so better management may be provided for good prognosis.

Pediatric Pulmonology strives to uphold the strongest ethical standards in publishing and to serve our diverse, international community of authors and readers with respect. We will be vigilant to prevent recurrence of this and other out-of-date, harmful terminology.

Background: Inappropriate humidification of inspired gas during mechanical ventilation can impair lung development in extremely low birthweight (ELBW) infants. Humidification depends on multiple factors, such as the heater-humidifier device used, type of ventilation, and environmental factors. Few studies have examined inspired gas humidification in these infants, especially during high-frequency oscillatory ventilation (HFOV). Our objective was to compare humidity during HFOV and intermittent positive pressure ventilation (IPPV), in vitro and in vivo. Methods: In-vitro and in-vivo studies used the same ventilator during both HFOV and IPPV. The bench study used a neonatal test lung and 2 heater-humidifiers with their specific circuits; the in-vivo study prospectively included preterm infants born before 28 weeks of gestation.  Results: On bench testing, mean absolute (AH) and relative (RH) humidity values were significantly lower during HFOV than IPPV (RH = 79.4% ± 8.1% vs 89.0% ± 6.2%, P<0.001). Regardless of the ventilatory mode, mean relative humidity significantly differed between the 2 heater-humidifiers (89.6% ± 6.7% vs 78.7% ± 6.8%, P=0.003). The in-vivo study included 10 neonates (mean ± SD gestational age: 25.7 ± 0.9 weeks and birth weight: 624.4 ± 96.1 g). Mean relative humidity during HFOV was significantly lower than during IPPV (74.6% ± 5.7% vs 83.0 ± 6.7%, P=0.004).  Conclusion: Relative humidity was significantly lower during HFOV than IPPV, both in vitro and in vivo. The type of heater-humidifier also influenced humidification. More systematic measurements of humidity of inspired gas, especially during HFOV, should be considered to optimize humidification and consequently lung protection in ELBW infants.

This report entails a case of an 11-year-old Chinese boy with cystic fibrosis (CF), who bears the c.1521_1523delCTT/c.3874-4522A>G genotype, which is extremely rare in Chinese population. Notably, the deep intron mutation c.3874-4522A>G was the first time identified among Chinese patients, which was reported mainly associated with mild phenotype. It is generally considered that a mild allele sustains CFTR function in a dominant fashion, even if paired with a severe allele. However, in the present report, the c.3874-4522A>G mutation was found related to severe pulmonary diseases, including early symptom onset, progressive bronchiectasis, recurrent airway P. aeruginosa combined with MRSA, rapid decline of lung function, and poor weight gain, which suggesting severe phenotype. Despite intensive chest care and optimized therapy, the child ultimately died of cardiopulmonary failure 3 months after discharge.

Background: Multisystem Inflammatory Syndrome in Children (MISC) is a phenomenon that appeared in children infected with or exposed to SARS-CoV-2. The typical onset of MISC is 4-6 weeks following SARS-CoV-2 infection and is formulated to be due to an immune response. Methods: Our study retrospectively analyzed data from a tertiary center in UAE of MISC patients who were admitted to either general pediatric wards or pediatric intensive care (PICU) or who came exclusively for follow-up (post PICU admission) from May 2020 to August 2021.   Results: The total sample size is 50 patients and the study included a comparison of PICU admissions with none PICU admissions. The PICU sample size was 18 patients, 50% females, with mean age of 8.3 years all were previously healthy. PICU patients had deranged blood counts with a lower hemoglobin count, a more pronounced lymphopenia and thrombocytopenia along with hypoalbuminemia. PICU patients presented with relatively higher inflammatory markers: CRP, PCT, ferritin and D-dimer. Immunological studies were significantly higher for IL-6 levels in PICU patients. On echocardiography, higher myocardial dysfunction was more notable in patients admitted to PICU. Children admitted in PICU were provided with more extensive therapy. As part of our study course, we re-evaluated our PICU patients twice, once at 48 hours post PICU admission and again 4-6 weeks after discharge from the hospital. No deaths have been recorded in the cohort. Conclusion: This study evaluated risk factors of MISC and potential severity features. Follow up of patients on discharge showed improvement across all domains.

We describe a case of unilateral phrenic nerve palsy due to SARS-COV-2 in a young child, which led to prolonged and complicated ventilation. The child was treated with methylprednisolone and IVIG, which led to a complete recovery of phrenic function. Temporary involvement of the phrenic nerve should be considered in children infected with SARS-COV-2 requiring prolonged ventilation. The phrenic nerve palsy is postulated to be due to peripheral nerve involvement by SARS-CoV-2. In South Africa, children under 12 years of age are not prioritized for SARS-CoV-2 vaccination. This case re-iterates that even though SARS-CoV-2 disease is mild in the vast majority of children there are more severe presentations which, in low- or middle-income countries, might even go unrecognized.

Background: Lung function in children with persistent asthma may be impaired during preschool and school ages. The aim of this study was to describe if some preschool IOS parameters are related to spirometry alterations on reaching school age. Methods: 66 children under six years old diagnosed with persistent asthma were studied prospectively with IOS during their preschool years and spirometry at school age. Results: The mean age was 4.9 years at the first evaluation and 7.9 years at the second evaluation, and 59.1% were male. During preschool, R5, Fres, AX, and D5-20 were found to have diagnostic accuracy (AUC>0.7) for predicting altered spirometry during school age (defined as FEV1 and/or FEV/FVC and/or FVC values below the lower limit of normality according to Quanjer predictive values). AX, D5-20, and R5 had the best LR+ to increase the probability of altered spirometry (50, 10, and 7.1, respectively). R5 was the best IOS parameter for discriminating bronchodilator response (BDR) in schoolchildren (AUC=0.7, LR+ = 3.7). Abnormal IOS increases the risk of having abnormal spirometry (RR=12.7, p= 0.002). This risk is even higher in atopic patients (RR= 21, p=0.003). Conclusion: The findings of this study indicate that some IOS parameters between 3 and 5 years of age are useful for predicting abnormal spirometry and BDR at school age.

BACKGROUND: Mathematical models based on the physiology when programmed as a software can be used to teach cardiorespiratory physiology and to forecast the effect of various ventilatory support strategies. We developed a cardiorespiratory simulator for children called “SimulResp”. The purpose of this study was to evaluate the quality of SimulResp. METHODS: SimulResp quality was evaluated on accuracy, robustness, repeatability and reproducibility. Blood gas values (pH, PaCO 2, PaO 2 and SaO 2) were simulated for several subjects with different characteristics and in different situations and compared to expected values available as reference. The correlation between reference and simulated data was evaluated by the coefficient of determination and Intraclass correlation coefficient. The agreement was evaluated with the Bland & Altman analysis. RESULTS: SimulResp produced healthy child physiological values within normal range (pH 7.40 +/- 0.5; PaCO2 40 +/- 5 mmHg, PaO2 90 +/- 10 mmHg; SaO2 97% +/- 3%) starting from a weight of 25 to 35 kg, regardless of ventilator support. SimulResp failed to simulate accurate values for subjects under 25 kg and/or affected with pulmonary disease and mechanically ventilated. Based on the repeatability was considered as excellent and the reproducibility as mild to good. SimulResp’s prediction remains stable within time. CONCLUSIONS: The cardiorespiratory simulator SimulResp requires further development before future integration into a clinical decision support system.

To the editor: We present a 13-year-old boy with mild persistent asthma and obstructive sleep apnea who initially presented with fever, dyspnea, cough, night sweats and myalgia for 4 days. He reported having an intermittent “hacking cough” for years. Physical examination was significant for diffuse crackles in the right lung base, decreased breath sounds and mild digital clubbing. Initial chest x-ray (CXR) revealed right middle lobe (RML) and right lower lobe (RLL) opacities with right pleural effusion interpreted and treated as community acquired pneumonia. He was followed as an outpatient by his pediatrician and referred to our pediatric pulmonology clinic months later for persistent RLL atelectasis and chronic cough. He was well appearing with similar physical examination findings as described earlier. Laboratory tests including sweat chloride, cystic fibrosis genetic panel, immunoglobulin levels, complement, pneumococcal and tetanus titers were normal.

CorrespondenceTitle: An oversight regarding the Club cell?To the Editor,I was surprised to a see a title including the outdated term “Clara Cell” protein, in reference to CC16, in the title and body of the article by Rallis et al recently published in Pediatric Pulmonology (1). It appears that there needs to be an ongoing reminder that due to the association of Dr. Max Clara with the Third Reich and his unethical medical research practices which lead to the identification of this cell type (2-4) that his name was removed in 2013.In 2012, Editorial boards of American Thoracic Society, the European Respiratory Society and the American College of Chest Physicians, based on recommendations from an expert panel assembled by the Forum of International Respiratory Societies, agreed to convert to use of the terms “club cell (Clara)” and “club cell secretory protein (Clara), and after January 1, 2013, completely transitioning out the use of the (Clara) eponym.In our day, where cancel culture is so predominant, questions have been raised about what lessons are lost when history is erased. Assuming an oversight was made by the authors, editors and reviewers in not utilizing the now accepted terms “Club cell secretory protein” or bronchiolar exocrine cells, it would only be acceptable to mention the prior term in the setting of an asterisked description explaining the context and involvement of concentration camp prisoners and their association with the prior eponym, for educational purposes.Rallis D, Baltogianni M, Dermitzaki N, Balomenou F, Papastergiou E, Maragoudaki E, Tsabouri S, Makis A, Giapros V. Clara cell protein expression amongst infants with respiratory distress syndrome. Pediatr Pulmonol. 2022 Mar 18.Woywodt A, Lefrak S, Matteson E. Tainted eponyms in medicine: the ”Clara” cell joins the list. Eur Respir J. 2010 Oct;36(4):706-8Winkelmann A, Noack T. The Clara cell: a ”Third Reich eponym”? Eur Respir J. 2010 Oct;36(4):722-7.Irwin RS, Augustyn N, French CT, Rice J, Tedeschi V, Welch SJ; Editorial Leadership Team. Spread the word about the journal in 2013: from citation manipulation to invalidation of patient-reported outcomes measures to renaming the Clara cell to new journal features. Chest. 2013 Jan;143(1):1-4.