Children are not small adults, and this fact is particularly true when we consider the respiratory tract. The anatomic peculiarities of the upper airway make infants preferential nasal breather between 2 and 6 months of life. The paediatric larynx has a more complex shape than previously believed, with the narrowest point located anatomically at the subglottic level and functionally at the cricoid cartilage. Alveolarization of the distal airways starts conventionally at 36-37 weeks, but occurs mainly after birth, continuing until adolescence. The paediatric chest wall has unique features that are particularly pronounced in infants. Neonates, infants and toddlers have a higher metabolic rate, and consequently, their oxygen consumption at rest is more than double that of adults. The main anatomical and functional differences between paediatric and adult airways contribute to understanding of various respiratory symptoms and disease conditions in childhood. Knowing the peculiarities of paediatric airways is helpful in the prevention, management and treatment of acute and chronic diseases of the respiratory tract. Developmental modifications in the structure of the respiratory tract, in addition to immunological and neurological maturation, should be taken into consideration during childhood.

Abstract INTRODUCTION: Effective Airway Clearance Techniques (ACT) is the key step in the management of Bronchiectasis. The aim of this study was to evaluate the efficacy of 3% Hypertonic Saline (HS) pre-medication in ACT in children with non Cystic Fibrosis (non-CF) bronchiectasis. METHODS: Five to 15 year old children with non-CF bronchiectasis were randomized either to receive 200µg of inhaled salbutamol followed by hypertonic saline nebulization (test) or only 200µg of inhaled salbutamol, prior to chest physiotherapy which is the conventional ACT (controls) for 8 weeks. After completion of first phase both groups went through one month washout period, before being crossed over to the opposite arms in the second phase. Spirometric parameters were recorded at the end of each phase. RESULTS: Fifty two children completed the study. Baseline characteristics of the two groups were similar. A significantly higher mean improvement was seen in predicted Forced Expiratory Volume in one second(FEV1) in the HS arm during phase 1 [HS=14.15±5.50 vs. conventional =5.04±5.55, p=0.001] and phase II [HS =10.81±5.51 vs. conventional =3.54 ±5.13, p=0.001]. HS arm showed a significantly higher mean improvement in predicted Forced Vital Capacity(FVC) in phase I[HS=13.77±5.73 vs. conventional= 7.54±4.90, p=0.001] and phase II, [HS=9.42±7.00 vs. conventional =4.42±4.00, p=0.003). Mean number of exacerbations experienced by a single child during phase I (2 months) were significantly less (p=0,001) in HS group compared to that of conventional group. CONCLUSIONS: Incorporating HS nebulization into ACT is an effective strategy to improve dynamic lung volumes and morbidity in children with non-CF bronchiectasis.

Congenital pulmonary airway malformation (CPAM), previously known as congenital cystic adenomatoid malformation (CCAM), is a rare developmental lung abnormality with the potential for malignant transformation. Bronchioloalveolar carcinoma (BAC), pleuropulmonary blastoma (PPB), rhabdomyomatous dysplasia/rhabdomyosarcoma (RMS) have been associated with CPAM. We report an unusual case of a 1-day-old male newborn who underwent lobectomy for a cystic lung lesion, which was found to be a mucinous BAC with K-ras mutation in a type 1 CPAM. The case supports the relationship between type 1 CPAM and BAC/KRAS mutant, and highlights that the malignant transformation can occur in very early stage of the infancy.

A document by Kam-lun Ellis Hon. Click on the document to view its contents.

To assess the impact of COVID-19 restrictions on cystic fibrosis (CF) pulmonary exacerbations (PEx) we performed a retrospective review of PEx events at our CF Center and compared the rate of PEx in 2019 vs 2020. Restrictions on social interaction due to the COVID-19 pandemic were associated with a lower rate of PEx at our pediatric CF Center, suggesting that these restrictions also reduced exposure to other respiratory viral infection in children with CF.

The FLNA gene encodes filamin A, an actin filament cross-linking protein that is ubiquitously expressed within the body. FLNA mutation causes periventricular nodular heterotopia (PVNH) and congenital heart disease. Interstitial lung disease (ILD) related to FLNA mutation has also been reported from 2011 and can be lethal. However, there are no reports of how to combine the treatment of heart disease with the conflicting treatment of lung disease. We herein report cases of two girls with FLNA mutation and both ILD and left-to-right shunts due to congenital heart disease. They presented with respiratory symptoms in early infancy and required management with long-term intubation and ventilation. However, their respiratory status improved subsequent to the closure of their left-to-right shunts even though they were small shunts with improvement in pulmonary hypertension. This suggests that early intervention with closure of cardiac shunts can prevent further deterioration of lung damage.

Background: HHe-3 MR is a non-invasive imaging method which maps and quantifies regions of ventilation heterogeneity (VH) in the lung. VH is an important feature of asthma, but little is known as to how VH informs patient phenotypes. Purpose: To determine if VH indicators quantified by HHe-3 MRI predict phenotypic characteristics and map to regions of inflammation in children with problematic wheeze/asthma. Methods. Sixty children with poorly-controlled asthma underwent HHe-3 MRI, including 22 with bronchoalveolar lavage (BAL). The HHe-3 signal intensity defined four ventilation compartments. The non-ventilated and hypoventilated compartments divided by the total lung volume defined a VH index (VHI %). Results: Children with VHI % in the upper quartile had significantly greater airflow limitation, bronchodilator responsiveness, blood eosinophils, expired nitric oxide (FeNO), and BAL eosinophilic/ neutrophilic granulocyte patterns compared to children with VHI % in the lower quartile. Lavage return from hypoventilated bronchial segments had greater eosinophil % than from ventilated segments. Conclusion: In children with asthma, greater VHI % as measured by HHe-3 MRI identifies a severe phenotype with higher type 2 inflammatory markers, and maps to regions of lung eosinophilia. Listed on ClinicalTrials.gov (NCT02577497).

Objective: Children with Down syndrome (DS) have an increased prevalence of obstructive sleep apnoea (OSA). Non-invasive ventilation (NIV) is a common modality of OSA treatment in this cohort. This study aimed to measure adherence and efficiency of NIV delivery in children with DS. Study design: This was a retrospective cohort study involving 106 children with confirmed OSA and home NIV with downloadable data capacity. Children were divided into DS (n=44) and non-DS cohorts (n=62). Adherence, clinical outcomes apnoea-hypopnoea index (AHI), positive airway pressure delivery and leakage were recorded and compared between DS and non-DS cohorts and within the DS cohort based on past surgical history. Results: Significantly greater NIV usage was observed in the DS cohort, they showed more consistent use with an increased percentage of days used relative to their non-DS counterparts (78.95 ± 2.26 versus 72.11 ± 2.14, p=0.031). However, despite greater usage, poorer clinical outcomes in the form of increased AHI (p=0.0493) was observed in the DS cohort, where significantly greater leakage was also shown 41.00 ± 1.61L/min versus 36.52 ± 1.18L/min (p=0.022). Twenty children with DS had prior cardiac surgery; compliance across all parameters was significantly reduced relative to those without. Conclusions: These data confirm that satisfactory NIV adherence is achievable in children with DS. However, we have identified excessive system leak at the machine-patient interface as a factor, which could undermine NIV efficacy in children with DS.

Background Normal values (>80%) of Forced Expiratory Volume in one second (FEV1) in patients with Cystic fibrosis (CF) may lead to the interpretation that there is no lung disease. This study is a comprehensive analysis of lung involvement in CF patients having normal FEV1. Methods Patients were recruited from two CF Centers: Hadassah Medical Center, Jerusalem and Vall d’ Hebron Hospital, Barcelona. Lung disease was assessed by lung clearance index (LCI), chest CT-Brody Score, respiratory cultures, number of pulmonary exacerbations (PEx) and days of antibiotic treatment in the year prior to the assessment. Results Of the 247 patients, 89 (36%) had FEV1 ≥80% and were included in the study (mean age 17.6 range 4.25-49 years). Chronic P. aeruginosa infection was found in 21%, and 31% had at least one major PEx in the year prior to the study. Abnormally elevated LCI was found in 86% of patients, ranging between 7.52-18.97, and total Brody score (TBS) was abnormal in 92% (range 5.0-96.5). Patients with chronic P. aeruginosa had significantly higher LCI (p=0.01) and TBS (p=0.01) which were associated with more major PEx (p = 0.04 and p<0.001, respectively) and more days of intravenous (IV) antibiotic treatment in the preceding year (p=0.03 and p=0.002, respectively). Conclusions Most CF patients with normal FEV1 have already physiological and structural lung abnormalities which were associated with more PEx and IV antibiotic treatment.

Objective: To determine whether viral coinfection is a risk for severe lower respiratory tract infection (LRTI). Working Hypothesis: Children with viral coinfection had a higher risk for admission to the intensive care unit (ICU) than those with a single virus infection. Study Design: Retrospective, observational study for ten years. Patient-Subject Selection: Children between 1-60 months of age hospitalized with LRTI. Methodology: We defined severe LRTI as admission to the ICU for high-flow nasal cannula oxygen/bilevel positive airway pressure/invasive ventilation and assessed demographic and laboratory data with potential risk factors from the patients’ medical records. Results: Of 2115 children hospitalized with LRTI, 562 had severe, and 1553 had mild disease. Viral coinfection was present in 28.3% of all patients, and those with viral coinfection were at a higher risk of severe LRTI than those with a single virus infection (43.8% vs. 22.7%; aOR, 3.44; 95% CI, 2.74-4.53). Respiratory syncytial virus (RSV) and rhinovirus (except for between 25-60 months) coinfections were associated with severe LRTI in all ages, whereas parainfluenza virus-3 (PIV3; 7-24 months) and bocavirus (7-12 months) coinfections led to severe LRTI in early childhood. Moreover, influenza-A coinfection caused severe LRTI in children between 7-12 and 25-60 months. Other risk factors included young age, prematurity, history of atopy, exposure to tobacco smoke, underlying condition, neutrophilia, lymphopenia, and high CRP value. Conclusion: Children with viral coinfection, particularly with rhinovirus, RSV, influenza-A, PIV3, and bocavirus, may be followed closely regarding the clinical changes.

Malnutrition and swallowing disorders are common in Duchenne muscular dystrophy (DMD) patients. We assessed, in adult DMD with HMV (home mechanical ventilation) and cough assist device, its prevalence and the relationships with respiratory muscle strength and long-term respiratory prognosis. We reviewed the patients (n=117, age 18 to 39 years (median 24)), followed in a reference center, from 2006 to 2015, to obtain clinical baseline, nutritional status, vital capacity (VC), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP). Median body mass index was low (15.6). Prevalence of malnutrition, swallowing disorders and gastrostomy were respectively 62, 34 and 11%. BMI and serum albumin level were significantly associated with MIP, MEP and VC. The 1/5-years cumulative incidences of respiratory events (pulmonary sepsis and acute respiratory distress) were respectively 20.7/44.5%. Using univariate analysis, predictive factors for respiratory events were swallowing disorders (p=0.001), transthyretinemia (p=0.034), MIP (p=0.039) and MEP (p=0.03) but not BMI or albuminemia. Using multivariate analysis, only swallowing disorders remained significantly associated with respiratory events (OR=4.2, IC95% 1.31-12.2, p=0.01). If prevalence of malnutrition and swallowing disorders are high in adult DMD on HMV, and respiratory muscles strength associated with serum albumin level and BMI, respiratory prognosis is mainly related to swallowing disorders.

Abstract Background: The effects of minimally invasive surfactant administration (MISA) in preterm infants with neonatal respiratory distress syndrome (NRDS) are unclear. Methods: We searched randomized controlled trials (RCTs) and compared MISA techniques with intubation for surfactant delivery in preterm infants with NRDS in PubMed, Embase, Cochrane Library, and Web of Science. Results: Thirteen RCTs (1931 infants) were included in the meta-analysis. The use of MISA techniques decrease the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks, pneumothorax, and hemodynamically significant patent ductus arteriosus (hsPDA) (Risk Ratio(RR) : 0.59, 95% confidence interval (CI) : 0.46 to 0.75, p < .0001; RR : 0.60, 95% CI : 0.39 to 0.93, p= .02 and RR : 0.88, 95% CI : 0.78 to 1.00, p= .04, respectively). In addition, infants in the MISA group required less mechanical ventilation within 72 h of life or during hospitalization (RR : 0.60, 95% CI : 0.48 to 0.75, p< .00001 and RR : 0.64, 95% CI : 0.49 to 0.82, p = .0005, respectively) compared with infants in the control group. However, the rate of surfactant reflux was higher in the MISA group than that in the control group (RR : 2.12, 95% CI : 1.37 to 3.29, p = .0008). There were no significant differences in mortality and other outcomes beteween the MISA group and the control group. Conclusions: The administration of surfactant with MISA techniques could lower the requirement for mechanical ventilation, and decrease the incidence of BPD at 36 weeks, pneumothorax, and hsPDA.

Pulmonary defects are reported in pectus excavatum but the physiological impact on exercise capacity is unclear. To test the hypothesis that pectus deformities are associated with a pulmonary impairment during exercise we performed a retrospective review on pectus patients in our center who completed a symptom questionnaire, cardiopulmonary exercise test, pulmonary function tests (PFT), and chest magnetic resonance imaging. Of 259 patients studied, dyspnea on exertion and chest pain was reported in 64% and 41% respectively. Peak oxygen uptake (VO2) was reduced in 30% and classified as mild in two-thirds. A pulmonary limitation during exercise was identified in less than 3%. Ventilatory limitations on PFT was found in 26% and classified as mild in 85%. Obstruction was the most common abnormal pattern (11%) followed by a nonspecific ventilatory limitation and restrictive pattern (7% each). There were no differences between patients with normal or abnormal PFT patterns for the anatomic degree of pectus malformation, VO2, or percentage reporting dyspnea or chest pain. Scatter plots demonstrated significant inverse relationships between severity of the pectus deformity with lung volumes on PFT and VO2 but no correlation between the severity of the pectus deformity and lung volumes during exercise. We conclude that resting lung volume measurements were associated with the anatomic degree of pectus severity but respiratory limitations during maximal exercise are uncommon and PFT patterns have poor correlation with symptomatology or VO2. These findings suggest non-respiratory causes are more likely for the high rates of dyspnea and reduced aerobic fitness reported in pectus.

OBJECTIVES: The primary objective of this study was to compare the therapeutic predictive value of area under the curve (AUC24) versus maximum concentration (Cmax) in cystic fibrosis (CF) patients receiving intravenous (IV) tobramycin for a Pseudomonas aeruginosa (PsA) acute pulmonary exacerbation (APE). Acute kidney injury (AKI) incidence and the relationship between time undetectable and efficacy were also assessed. METHODS: A retrospective review was conducted in patients aged at least one month with a diagnosis of CF receiving IV tobramycin for treatment of a PsA APE and admitted to the University of Kentucky between August 2015 and August 2019 . Patients were excluded if they had no growth of PsA on sputum culture or if two post-dose tobramycin levels were not obtained following a dose adjustment of ≥20%. RESULTS: A total of 44 pediatric and 107 adult patient encounters met inclusion criteria. In patients with therapeutic success (n=91), 75.8% had an AUC24 ≥80 and 80.3% had a Cmax ≥8 times the highest PsA minimal inhibitory concentration (MIC). There was a significant correlation between AUC24 and Cmax (r2 = 0.727; p<0.001). AKI incidence was significantly higher in patients receiving IV tobramycin dosed multiple times daily versus at least every 24 hours (50% versus 28.7%; p=0.047). CONCLUSIONS: The results of this study indicate that both AUC24 and Cmax serve as relatively accurate predictors of tobramycin efficacy. Additionally, given the significant increase in incidence of AKI, multi-daily dosing of IV tobramycin should be used only in select pediatric and adult patients with CF.

Background: A series of repeated questionnaire surveys among 8- and 9-year-old schoolchildren in the city of Patras, Greece, demonstrated a continuous rise in the prevalence of wheeze/asthma from 1978 to 2003, with a plateau between 2003 and 2008. We further investigated wheeze/asthma trends within the same environment during the last decade. Methods: Two further identical cross-sectional surveys were conducted in 2013 (N=2554) and 2018 (N=2648). Physician-diagnosed wheeze and asthma were analysed separately and in relation to their occurrence (recent-onset: solely within the last two years; non-current: prior to the last two years; persistent: both before and within the last two years). In addition, in 2018, spirometry was performed in participants reporting relevant symptoms and in a random sample of healthy controls. Results: The prevalence of current wheeze/asthma declined from 6.9% in 2008 to 5.2% in 2013 and 4.3% in 2018. The persistent and non-current wheeze/asthma groups (both including children with symptoms at preschool age) followed this overall trend, while the prevalence of recent-onset wheeze/asthma remained unchanged. Persistent and non-current wheezers were also more frequently diagnosed with asthma, in contrast to those with recent-onset wheeze. Children with recent-onset wheeze/asthma and a considerable fraction of those with persistent symptoms had lower lung function. Conclusions: The prevalence of childhood wheeze/asthma has declined significantly during the last decade in Greece. Our analysis suggests that the reversing trend is most likely attributed to changing asthma perceptions among physicians and/or parents, especially in the case of preschool children with troublesome respiratory symptoms.

BackgroundAspirations are frequent in children with neurological impairment. They significantly increase the risk for acute and chronic respiratory insufficiencies leading to high morbidity and mortality. Laryngeal sensation deficits have been linked to aspirations in adults and are a suspected cause for dysphagia in children. In a similar neurological circuit as swallowing, laryngeal receptors trigger coughing as a protective airway reflex. The aim of this study was to examine the association between impaired laryngeal sensation (ILS), aspiration and coughing in neurologically impaired children.Design and MethodsIn a retrospective study, 110 children with suspected dysphagia who underwent a clinical evaluation of swallowing and a flexible endoscopic evaluation of swallowing (FEES) between 2013 and 2019 in the children’s university clinic Düsseldorf were analyzed. Laryngeal sensation was tested by the endoscopic touch method. Associations were computed using χ2-test.ResultsFifty-four patients (49.1%) had neurological impairment, 56 patients (50.9%) had no or other comorbidities and served as a control cohort. Children with neurological impairment suffered from ILS significantly more often than children with no or other comorbidities (χ²(1) = 4.63, p = .031). ILS was associated with all other FEES variables but did not correlate with coughing. The symptom coughing correlated with aspiration in the group of neurologically impaired children and in children ILS.Conclusion ILS is a potential cause of aspirations in children with neurological impairment.  Physicians need to pay special attention to the occurrence of coughing in children with neurological impairment and/or ILS since it signals aspirations that took place.

Objective Our objective was to test the hypothesis that in-hospital respiratory viral infections (RVI) would be significantly lower in a cohort of patients with established bronchopulmonary dysplasia in the SARS-CoV-2 era when compared to historical controls. Study Design On April 1, 2020, we implemented a universal infection prevention bundle to minimize the risk of nosocomial SARS-CoV-2 transmission in a dedicated BPD intensive care unit. We performed a retrospective cohort study and included patients with established BPD, as defined by the 2019 Neonatal Research Network criteria, admitted to our center who underwent real-time polymerase-chain-reaction RVI testing between January 1, 2015 and March 31, 2021. We excluded patients re-admitted from home. We compared to number of tests performed, the proportion of positive tests, and the distribution of viral respiratory pathogens in the pre- and post-SARS-CoV-2 eras. Results Among 176 patients included in the sudy, 663 RVI tests were performed and 172 (26%) tests were positive. The median number of tests performed, measured in tests per patient per month, in the SARS-CoV-2 era was not significantly different compared to the pre-SARS-CoV-2 era (0.45 vs 0.34 tests per patient per month, P = 0.07). The proportion of positive RVI tests was significantly lower in the SARS-CoV-2 era when compared to the pre-SARS-CoV-2 era (0.06 vs 0.30, P<0.0001). No patients tested positive for SARS-CoV-2 in the SARS-CoV-2 era. Conclusions Infection prevention measures developed in response to the SARS-CoV-2 pandemic may reduce the risk of RVIs in hospitalized patients with established BPD.

Successful Extubation in Preterm InfantsTo the Editor,I read with great interest the article by O’Connor et al1 describing factors that lower the likelihood of successful extubation by day 14 in mechanically ventilated neonates with or at risk of developing bronchopulmonary dysplasia (BPD), born at <30week gestational age (GA). These factors were younger GA at birth, and at the time of commencing steroids had higher MAPs and had higher oxygen requirements. They studied 287 neonates and noted that each additional week of GA at birth led to a 1.53 increase in the odds of successful extubation. Higher average fraction of inspired oxygen (FiO2) requirements in the preceding 24 h resulted in a 0.94 decrease in the odds of successful extubation and higher mean airway pressure (MAP) resulted in 0.76 decrease in odds of successful extubation.I have been using the probability of successful extubation calculator (http://extubation.net/), which incorporates the same factors as described by Connor et al 1. The calculator was described earlier by Gupta et al 2. They incorporated GA, MAP and FiO2 in the calculation, same as Connor et al 1. The only difference was the inclusion of the respiratory severity score (RSS), which is nothing but a product of MAP and FiO2 [(RSS= mean airway pressure (cm H2O) x FiO2 (0.21-1.00)].Although, we have a probability score model for successful extubation among preterm infants, as described by Gupta et al 2, I do agree with Connor et al 1 that we need to develop prognostic scoring model for intubated preterm infants.References:O’Connor K, Hurst C, Llewellyn S, Davies M. Factors associated with successful extubation following the first course of systemic dexamethasone in ventilator-dependent preterm infants with or at risk of developing bronchopulmonary dysplasia [published online ahead of print, 2022 Jan 7]. Pediatr Pulmonol . 2022;10.1002/ppul.25821. doi:10.1002/ppul.25821Gupta D, Greenberg RG, Sharma A, et al. A predictive model for extubation readiness in extremely preterm infants. J Perinatol . 2019;39(12):1663-1669. doi:10.1038/s41372-019-0475-xAuthor:Shabih Manzar, MDLouisiana State University Health Sciences CenterDepartment of Pediatrics1501 Kings HighwayShreveport, LA 71103Phone: 318-626-1623Fax: 318-675-6059Email: [email protected] contribution: Dr. Manzar wrote the draft.Funding and financial support: NoneConflict of interest: None