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 We will be vigilant to prevent recurrence of this and other out-of-date, harmful terminology.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.

Background: Studies report associations between maternal mental health and adverse respiratory outcomes in children; however, the impact of timing and duration of maternal distress remains understudied. We sought to longitudinally examine associations between maternal depression and childhood asthma and wheeze, and explore sex differences. Methods: Maternal depression (n=605) were assessed using the Edinburgh Depression Scale questionnaire, dichotomized at a clinically relevant cutoff (>12) a) during pregnancy, b) postpartum, and c) postpartum and subsequent time points postnatally (recurrent depression). Report of wheeze in the past 12 months (current wheeze) and asthma were obtained using a validated survey at 48 and 72 months. Associations were analyzed using a modified Poisson regression adjusted for covariates, and in interaction models. Results: Both postpartum and recurrent depression were associated with higher risk of current wheeze (RR: 1.88, 95% CI: 1.21, 2.92; RR: 2.39, 95% CI: 1.52, 3.78) and asthma at 48 months (RR: 2.79, 95% CI: 1.13, 6.87; RR: 3.14, 95% CI: 1.26, 7.84). In interaction analyses, associations were stronger in females. Postpartum and recurrent depression were associated with higher risk of current wheeze at 48 months in females (RR: 3.06, 95% CI: 1.48, 6.32; RR: 4.02, 95% CI: 1.91, 8.46) when compared to males RR: 1.47, 95% CI: 0.84, 2.56; RR: 1.86, 95% CI: 1.04, 3.34). Conclusions: Postpartum and recurrent depression were associated with higher risk of wheeze and asthma in children, and associations were stronger in females than males. Understanding the temporal- and sex-specific effects of maternal depression may better inform prevention strategies.

To our knowledge this is the first published case of NP associated with COVID-19 in an individual with CF and the first associated with Nocardia infection. We suspect the combination of cystic fibrosis, COVID-19 pneumonitis and co-infection with Nocardia farcinia caused this young man’s NP and ultimately his untimely death. We hope this case will highlight individuals with CF of all ages are at risk of severe COVID-19 infection.

Foreign body aspiration is rare in children below 6 months of age. Very young children presenting with stridor, atypical croup presentation, and not responding accordingly, subglottic foreign body aspiration should be considered. These may not always be visible with bedside flexible endoscopy and may need investigation under anesthesia. We report 2 cases of devil's thorn aspiration in young infants. These children were left on the floor to play and devils thorn may be a danger lurking as the they have been deposited unknowingly by the shoes people wear and pick up by these young infants.

The literature has identified continued needs for children with cystic fibrosis. The profession of occupational therapy is uniquely equipped and trained to address a variety of needs that children with cystic fibrosis experience during daily life engagement, potentially filling this gap in services. Despite this, occupational therapists are rarely consulted or included in patient care plans. It is the goal of this letter that professionals working in the field of cystic fibrosis will gain an understanding and appreciation for the profession of occupational therapy when considering care plans for their patients.

Background:  Heterozygote carriers of potentially pathogenic variants in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene have increased asthma risk. However, the frequency and impact of CFTR variation among individuals with asthma is unknown. Objective: To determine whether potentially pathogenic  CFTR variants associate with disease severity and whether individuals with two potentially pathogenic variants exist in a severe asthma-enriched cohort . Methods: We analyzed sequencing data spanning a 190.5Kb region of  CFTR in participants from the Severe Asthma Research Program (SARP1-3). Potentially pathogenic, rare  CFTR variants (frequency<0.05) were classified as CF-causing or of varying clinical consequences (VVCC) (CFTR2.org). Regression-based models tested for association between  CFTR genotypes (0-2 potentially pathogenic variants) and severity outcomes. Results: Of 1401 participants, 9.5% (134) had one potentially pathogenic variant, occurring more frequently in non-Hispanic white (NHW, 10.1% [84 of 831]) compared to African American individuals (AA, 5.2% [22 of 426]). We found ≥2 potentially pathogenic  CFTR variants in 1.4% (19); 0.5% (4) of NHW and 2.8% (12) of AA. Potentially pathogenic  CFTR variant genotypes (≥1 or ≥2 variants) were not cumulatively associated with lung function or exacerbations. In NHW, we found three F508del compound heterozygotes with F508del and a VVCC (two 5T;TG12[c.1210-11T>G] and one Arg1070Trp) and a homozygote for the VVCC, 5T;TG12. Conclusions: We found potentially pathogenic  CFTR variants within a severe asthma-enriched cohort , including three compound heterozygote genotypes variably associated with CF in NHW individuals. These findings provide the rationale for  CFTR sequencing and phenotyping of CF-related traits in individuals with severe asthma.

ABSTRACT INtubation- SURfactant-Extubation (InSurE) approach is traditional method of surfactant delivery in preterm neonates with Respiratory Distress Syndrome (RDS). Newer, Less Invasive Surfactant Administration(LISA) techniques lessen the need for mechanical ventilation and its adverse consequences. Evidence on the favourable effects of LISA can’t be extrapolated from developed to developing countries. Aim of Study is to compare the effectiveness of InSurE and LISA. Objectives: Primary outcome was to find need of intubation and mechanical ventilation within 72 hrs of birth. Neonates were followed until discharge/death for adverse events and complications. Material & Methods: Open-label RCT was conducted at tertiary neonatal intensive care unit. Preterm neonates with diagnosis of RDS were randomized in two groups (InSurE or LISA) to receive surfactant soon after birth. Results: Total of 150 neonates were analysed (75 in each group). Insignificant Statistical difference was seen in the need for intubation and mechanical ventilation within 72 h of birth between the two groups [InSurE, 30 (40%) and LISA, 30(40%), relative risk 1.0, 95% confidence interval 0.68–1.48]. 12% (n=9, LISA group) & 14.6% (n=11 InSurE group) had adverse events during the procedure. Also, we observed insignificant statistical difference in the rates of major complications or duration of respiratory support, hospital stay & mortality. Conclusion: : LISA and InSurE are equally effective for surfactant administration in the treatment of RDS, when NIPPV is the primary mode of respiratory support. More RCTs are required to compare the efficacy & long-term outcomes of LISA with InSurE. Keywords- Intubation, Mechanical Ventilation, NIPPV.

The loss of function of the FLNA gene may result in impairment of the filamin A protein. Of the many clinical syndromes, this condition may produce lung disease. This usually presents itself and is diagnosed in the infant/toddler age group that may mimic broncho-pulmonary-dysplasia. It is part of the entities included in Childhood Interstitial Lung Disease (chILD) group of disorders. We are reporting on a patient that was diagnosed at eleven years of age. This case provides a unique insight into the long-term course of lung disease in this illness and broadens our understanding of the spectrum of its presentation. Although the patient had symptoms very early in life, the diagnosis may not have been entertained because of the rarity of the disorder, its atypical presentation, and discontinuous care due to parents moving to different cities for reasons of employment. Her initial presentation to our institution was for pneumonia. Due to the highly unusual chest x-ray images, asthenia, and early clubbing, an extensive work up was undertaken that included further imaging and a lung biopsy. The final diagnosis was confirmed by the detection of FLNA LOF gene mutation.

This study investigated whether Elexacaftor-Tezacaftor-Ivacaftor (Kaftrio ®), a cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator, could improve exercise capacity in adolescents with CF. After six weeks treatment, Kaftrio ® improved both maximal and submaximal indices of aerobic fitness. Improvements were independent of changes in ventilatory function during exercise and physical activity. Interestingly, pulmonary oxygen uptake per unit of power output was higher in two, out of three, cases who presented with more severe CF lung disease. These findings suggest improved O 2 extraction and/or consumption in the exercising muscle and demonstrate, for the first time, that short-term treatment with Kaftrio ® might improve aerobic fitness in people with CF, especially in those with more severe lung disease and deconditioning.