CorrespondenceTitle: An oversight regarding the Club cell?To the Editor,I was surprised to a see a title including the outdated term “Clara Cell” protein, in reference to CC16, in the title and body of the article by Rallis et al recently published in Pediatric Pulmonology (1).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.

Our case was a pediatric patient with very extensive lung involvement who also had involvement in other organs. We believe our case demonstrates clinical features that are complementary for the case series by Mfingwana L and colleagues and thus, will be beneficial for the readers.

Background: Inhaler technique (IT) knowledge among healthcare providers is poor. The aim was to improve PED healthcare providers’ IT technique by carrying out an education intervention, and sustain it for 6 months. Methods: open-label, quasi-experimental, prospective and unicentric study. Healthcare professionals working at the Pediatric Emergency Department (PED) were enrolled. The study was developed in three phases: baseline evaluation and education intervention (P1) and reevaluation 1 month (P2) and 6 months (P3) after the education intervention. Participants fulfilled an eight-question theoretical test. Practical skills were evaluated by demonstrating IT in all three phases. The education intervention consisted in a verbal explanation of IT followed by a demonstration of IT with metered-dose inhaler using a mannequin. Results: 84 healthcare providers (medical residents, nurses and nursing assistants) were involved. In the theoretical questionnaire, the mean score at baseline was 4.4/8 (SD 1.7) improving to 6.3/8 (SD 1.2) in P2 and 6.47/8 (SD 1.1) in P3. In the IT evaluation for children <7 years old, the score improved from 5.7/7 (SD1.3) to 6.5/7 in P2 and 6.7/7 in P3 (p<0.001). For children >7 years old, the mean score of IT at baseline was 3.1/10 (SD 4), which improved to 7.4/10 (SD3) and 8.2/10 in P2 and P3 respectively (p<0.001). Only laboral category influenced results at baseline. Conclusion: Healthcare providers’ theoretical knowledge and practical skills on IT are low. The education intervention performed is a useful strategy to ameliorate IT among healthcare providers.

Pleural drainage was differently performed in two similar neighboring hospitals (32.0 % vs. 58.2 %, p < 0.001), but the length of stay was shorter in the hospital using a more conservative approach (median 12 days vs. 18 days, p < 0.001). This result seemed unrelated to severity but associated with the shorter duration of intravenous treatment. This study adds to previous reports suggesting that pleural drainage is unnecessary in many cases; controlled studies are needed to determine which patients may actually benefit from its use.

Background and Objective: With improved survival in neonates with meconium aspiration syndrome (MAS), the focus is currently on mitigating the morbidities. The objective of this study was to predict factors determining prolonged hospital stay in neonates with MAS. Materials and methods: It was a retrospective cohort from five centres of south India between 2018 and 2020. Neonates ≥35 weeks of gestation admitted to NICU with the diagnosis of MAS and requiring oxygen beyond 24 hours of life were included in the study. The morbidities in the neonates with stay ≤7 days (short stay) were compared with >7 days (prolonged stay). Logistic regression by the backward stepwise method was used for predictive score creation. Results: Out of 347 neonates with MAS discharged home, 103 (29%) had a short stay and 244 (71%) had prolonged stay. The primary support beyond O2 (CPAP/MV) (42% vs 83%, p<0.001), FiO2 at 1hr>30% (45% vs 87%, p<0.001), HIE stage 2 or 3 (2% vs 27%, p<0.001), moderate-severe PPHN (3% vs 31%, p<0.001) were independent factors associated with prolonged stay on logistic regression. A prediction model was devised using weighted scores of these four associated morbidities. The clinical score thus developed had 83% sensitivity, 68% specificity for the prediction of prolonged stay [AUC- 82, 95% CI (78-87), p<0.001]. Conclusion: More than two-thirds of neonates with MAS had prolonged stay. The primary support beyond oxygen, Fio2 requirement >30%, Moderate to severe PPHN, HIE stage 2 or 3 were predictive of prolonged stay in neonates with MAS.

Context: In adults, permissive hypercapnia reduces mortality and ventilation duration. However, in preterm infants, findings from past research regarding the efficacy and safety of permissive hypercapnia are controversial. Objective: To evaluate the efficacy and safety of permissive hypercapnia versus normocapnia in preterm infants on mechanical ventilation. Data Sources: MEDLINE, EMBASE, CENTRAL, and CINAHL Study Selection: Published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were included. Data Extraction: Two reviewers independently screened the title and abstract and full text, extracted data, assessed the risk of bias, and evaluated certainty of evidence (CoE) according to the Grading of Recommendations Assessment, Development and Evaluation approach. A meta-analysis of RCTs was performed using the random-effects model. Results: Four RCTs (693 infants) and one cohort study (371 infants) were included. No significant differences existed between the permissive hypercapnia and normocapnia groups for bronchopulmonary dysplasia (BPD) (risk ratio [RR] 0.94; 95% confidence interval [CI] 0.74-1.18; very low CoE) and a composite outcome of death or BPD (RR 1.05; 95% CI 0.90-1.23; very low CoE). Permissive hypercapnia may increase necrotizing enterocolitis (RR 1.69; 95% CI 0.98-2.91; very low CoE), although the null or trivial effect cannot be excluded. No significant differences existed between the two groups for any other outcome assessed (very low-to-low CoE). Limitations: The sample sizes were less than the optimal sizes for all outcomes assessed, indicating the need for further trials. Conclusions: Permissive hypercapnia did not have any significant benefit or harm in preterm infants.

Background: Newborn screening (NBS) for cystic fibrosis (CF) has been underway universally in the USA for more than a decade, as well in most European countries, and algorithms have been evolving throughout this period with quality improvement projects as immunoreactive trypsinogen determinations alone have been transformed to a 2-tier strategy with DNA analyses. Objective: To apply next generation sequencing (NGS) as a method for expanding the DNA tier for identifying variants in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene with minimization of unintended outcomes. Design: Sequential quality improvement project in three phases using plan coupled to statewide follow up and analysis of screening outcomes in comparison to other NBS programs that use CFTR sequencing. Results: After demonstrating feasibility in the first phase, we studied an IRT/NGS algorithm that included CFTR Variants with Varying Clinical Consequences (VVCCs). This revealed a high identification of CF patients with 2-variants detected through screening, but for every CF case there were 1.4 with cystic fibrosis metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID). This led us to a third phase of quality improvement in which the VVCCs were eliminated except for R117H, resulting in 94% 2-variant detection of patients and 0.44:1 ratio of CRMS/CFSPID to CF. Conclusion: NGS can be used with IRT as an effective method of identifying infants at risk for CF without an appreciable increase in detection of either carriers or CRMS/CFSPID cases.

Objective(s): To determine the impact of Clostridioides difficile Infection (CDI) among pediatric Cystic Fibrosis (CF) hospitalizations using a large nationally representative pediatric hospital database . Study design: We identified Cystic Fibrosis-related hospitalizations during the years 1997 to 2016 in the Kids’ Inpatient Database [KID] and compared in-hospital mortality, Length of Stay [LOS], and hospital charges among hospitalizations with and without a coexisting diagnosis of C. difficile using logistic regression models for mortality and general linear models with gamma distribution and logarithmic transformation for LOS and hospital charges. We also evaluated temporal trends in the proportion of CF hospitalizations with concomitant CDI using data published triennially Results: We analyzed 21, 616 pediatric CF hospitalizations between the years 1997 to 2016 and found a total of 240 (1.1%) hospitalizations with concurrent CDI diagnosis. Adjusted analyses demonstrated an association of CDI with increased mortality (OR 5.2, 95% 95% CI 2.5-10.7), longer LOS (46.5% increment, 95% CI 36.0-57.1), and higher charges (65.8% increment, 95% CI 53.5-78.1) for all comparisons. The proportion of CF hospitalizations with CDI increased over time from 0.64% in 1997 to 1.73% in 2016 (p<0.001). Conclusion(s): As CDI is associated with excess mortality, LOS, and cost in children hospitalized for CF, efforts to reduce infection rates and aggressive diagnosis and treatment of active infections should be prioritized to improve hospital outcomes among children with CF.

Introduction Children with Down Syndrome (DS) are at high risk of sleep disordered breathing (SDB). We aimed to examine the burden of SDB in infants with DS referred to tertiary sleep center. Methods Infants (≤12 months old) with DS who underwent consecutive polysomnography (PSG) at a single academic sleep center over a 6-year period were included. OSA (obstructive apnea hypopnea index [oAHI]>1/hr), central sleep apnea (central apnea index>5/hr) and the presence of hypoventilation (% time spent with CO2 > 50 mmHg either by end-tidal or transcutaneous> 25% of total sleep time) and hypoxemia (time spent with O2 saturation <88% >5 min) were ascertained. For infants who underwent adenotonsillectomy (AT), we compared the SDB metrics before and after the AT. Results A total of 40 infants were included (Mean age 6.6 months, male 66%). PSGs consisted of diagnostic (n=13) and split night (n=27, 68%) studies. All met criteria for OSA with mean oAHI 34.6 (32.3). Central sleep apnea was present in 11 (27.5%) of infants. A total of 11 (27.5%) had hypoxemia. Hypoventilation was present in 10 (25%) infants. There was a trend of association between hypothyroidism and hypoventilation (OR: 5.5 [0.96-34.4], p=0.056). Among 13 infants who underwent AT and had a follow up PSG, severity of OSA markedly reduced after AT (oAHI difference: 34/hr [29], p=0.0002). Conclusion This study highlights the high prevalence of SDB in infants with DS and supports early PSG assessment in this patient population.

Vaping associated lung injury (EVALI) has increased in prevalence after first being noted in an outbreak among teenagers in 2019. Vaping involves the use of a heating device to aerosolize a product, typically nicotine or more recently, cannabinoids. Products that contain cannabinoids, such as CBD oil, are being used more as these products are easy to obtain and are typically less expensive. The clinical manifestations of EVALI are widespread and include respiratory symptoms as well as cardiogenic, gastrointestinal, and constitutive symptoms. EVALI rarely presents with hemoptysis as one of the main presenting symptoms, especially in an adolescent. This case will discuss EVALI with associated hemoptysis in a teenager secondary to vaping cannabinoid oil.