Background and aims Thoracic air leak syndrome (TALS) is a complication related to chronic pulmonary graft-versus-host disease (pGvHD) that affects approximately 0.83% to 3.08% patients after allogenic hematopoietic stem cell transplant. Such complication is defined as the occurrence of any form of air leak in the thorax, including spontaneous pneumomediastinum or pneumopericardium, subcutaneous emphysema, interstitial emphysema and pneumothorax and has a negative impact on post-transplant survival. The aim of the present study is to describe a single-center experience in the surgical management of recurrent TALS in adolescents and young adults and its outcome. Methods We retrospectively reviewed the clinical notes of patients with previous allogenic hematopoietic stem cell transplant who underwent surgical procedures for recurrent TALS from January 2016 until March 2021. As well we analyzed clinical data, number of episodes of thoracic air leak, surgical procedures and relative outcome. Results In the examined period, four patients, aged 16 to 25 years, underwent surgical procedures for TALS, including thoracostomy tube placement, thoracoscopic pleurodesis and thoracotomy. All the patients had been diagnosed with pGvHD before the onset of TALS, with a mean time lapse of 276 days (range 42 – 513). These patients experienced on average 4.5 air leak episodes (range 3 – 6). All the patients experienced at least two episodes before surgery. One patient underwent emergency tube thoracostomy only, three patients underwent thoracoscopic pleurodesis and two patients underwent thoracotomy. After surgery, patients were free from air leak symptoms for a mean time of 176 days (range 25 – 477). Pulmonary function progressively deteriorated, and all the patients eventually died because of respiratory failure after a mean time of 483 days (range 127 – 1045) after the first episode of air leak. Conclusions Surgery provides temporary relief to symptoms related to TALS. When TALS develops, pulmonary function progressively worsens toward respiratory failure and death.

CF is considered a rare disease among the non-Caucasian population. The clinical phenotypes and genotypic spectrum of Chinese CF patients are reported to be different from that observed in Caucasians[(1)](#ref-0001). Our patient carried compound heterozygous mutations which are not included in the Caucasian CFTR common mutation-screening panel and have not been reported yet. CFTR dysfunction causes a spectrum of diseases, with a range in the number of organs involved and varying disease severity. Typical phenotypic features of CF include respiratory diseases (bronchiectasis with persistent airway-based infection and inflammation), gastrointestinal diseases (meconium ileus (MI)), hepatobiliary manifestations (pancreatic insufficiency), and male infertility[(2)](#ref-0002). Our patient presented severe manifestations, namely colonic perforation, meconium thorax, severe pneumonia, diaphragmatic defects-caused marked diaphragm elevation and respiratory failure. It’s difficult to ascertain whether the diaphragmatic defects in our patient is related to CF. MI is often the first manifestation of CF and occurs in approximately 20% of CF patients. CF should therefore be high in the differential diagnosis of any infant presenting with MI[(3)](#ref-0003).

Title: Reply to Migration is not the perfect answer: Optimised methodology to assess LCI agreement between corrected legacy multiple breath nitrogen washout data and that directly collected on updated software.

VACTERL association is linked to multiple congenital anomalies including tracheoesophageal fistula. In rare cases, VACTERL has been complicated by other airway malformations including severe bronchial stenosis or unilateral pulmonary agenesis. We report a child who developed episodes of oxygen desaturation during sleep associated with high pressure support requirements to maintain ventilation. He was known to have VACTERL association as well as spinal muscular atrophy (SMA) type II, a genetic neuromuscular disorder. Children with SMA can show progressive respiratory symptoms, including intercostal muscle weakness and accompanying paradoxical abdominal breathing with sparing of diaphragm function. Our patient was very difficult to ventilate non-invasively despite high pressures. CT chest with dynamic airway evaluation showed bilateral bronchial stenosis. High inspiratory pressures with non-invasive ventilation as seen in our case are required to overcome stenotic airways but are not expected in neuromuscular respiratory failure.

Childhood interstitial lung disease (chILD) is a heterogeneous group of diffuse lung diseases (DLD) that can be challenging to diagnose. With relative rarity of individual entities, data are limited on disease prevalence, care patterns, and healthcare utilization. The objective of this study was to evaluate chILD prevalence and review diagnostic and clinical care patterns at our center. A single-center, retrospective cohort study was conducted of patients receiving care at the Children’s Hospital of Philadelphia (CHOP) between January 1, 2019, and December 31, 2021. Through query of selected ICD-10 billing codes relevant for chILD/DLD, a total of 306 patients were identified receiving care during this period. Respiratory symptom onset was documented to have developed before two years of age for 40% of cases. The most common diagnostic categories included those with oncologic disease (21.2%), bronchiolitis obliterans (10.1%), and connective tissue disease (9.5%). Genetic testing was performed in 49% of cases, while 36% underwent lung biopsy. Hospitalization at CHOP had occurred for 80.4% of patients, with 45.1% ever hospitalized in an intensive care unit. One-third of children had required chronic supplemental oxygen. Seven (2.3%) patients died during this three-year period. Collectively, these data demonstrate the scope of chILD and extent of health care utilization at a large volume tertiary care center. This approach to cohort identification and EMR-driven data collection in chILD provides new opportunities for cohort analysis and will inform the feasibility of future studies.

Childhood interstitial and diffuse lung disease (chILD) encompasses a broad spectrum of rare disorders. The Children’s Interstitial and Diffuse Lung Disease Research Network (chILDRN) established a prospective registry to advance knowledge regarding etiology, phenotype, natural history, and management of these disorders. This longitudinal, observational, multicenter registry utilizes single-IRB reliance agreements, with participation from 25 chILDRN centers across the U.S. Clinical data are collected and managed using the Research Electronic Data Capture (REDCap) electronic data platform. We report the study design and some elements of the initial Registry enrollment cohort, which includes 683 subjects with a broad range of chILD diagnoses. The most common diagnosis reported was neuroendocrine cell hyperplasia of infancy (NEHI), with 155 (23%) subjects. Components of underlying disease biology were identified by enrolling sites, with cohorts of interstitial fibrosis, immune dysregulation, and airway disease being most commonly reported. Prominent morbidities affecting enrolled children included home supplemental oxygen use (63%) and failure to thrive (46%). This Registry is the largest longitudinal chILD cohort in the U.S. to date, providing a powerful framework for collaborating centers committed to improving the understanding and treatment of these rare disorders.

Dear Editor, I am writing to submit a letter titled “Usage of a Novel Inhaler Device for the Management of Asthma in Children with Special Needs” for your consideration. This letter highlights the importance of the inhaler device technique in children with asthma when they have comorbid conditions such as attention-deficit/hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD). These comorbidities often make it challenging for physicians to plan a treatment regimen, as it impacts the patient’s adherence to medication. We evaluated the effectiveness of a breath-actuated inhaler (BAI) in managing poorly controlled asthma in three pediatric patients with special needs. All patients showed significant improvement in their asthma symptoms, were well-controlled after one month of using the BAI and they found that device was easy to use. This letter contributes to the growing body of evidence supporting the effectiveness of BAI in the management of asthma, particularly in children with special needs. We hope this work to be submitted under the letter to editor section and it will be of interest to your readership and contribute to improving asthma management in children with comorbidities. Thank you for your consideration.

A dynamic case report in which the authors present a multidisciplinary collaboration in a dyspnoic adolescent girl who coughs up blood, has a high temperature and rapidly progresses to respiratory failure. Laboratory findings, imaging results, and their interpretation are shown. Current recommended management is discussed.

Background: People with cystic fibrosis (PwCF) have chronic lung disease and may be at increased risk of COVID-19-related morbidity and mortality. This study aimed to determine seroprevalence and clinical characteristics of SARS-CoV-2 infection in children with CF, and to assess antibody responses following SARS-CoV-2 infection or vaccination. Methods: Children and adolescents with CF followed at Seattle Children’s Hospital were enrolled between July 20, 2020 and February 28, 2021. SARS-CoV-2 serostatus was determined on enrollment, at 6 and 11 months (+/-2 months) for nucleocapsid and spike IgG. Participants completed intake and weekly surveys inquiring about SARS-CoV-2 exposures, viral/respiratory illnesses, and symptoms. Results: Of 125 PwCF enrolled, 14 (11%) had positive SARS-CoV-2 antibodies consistent with recent or past infection. Seropositive participants were more likely to identify as Hispanic (29% vs 8%, p=0.04) and have pulmonary exacerbations requiring oral antibiotics in the year prior (71% vs 41%, p = 0.04). Five seropositive individuals (35.7%) were asymptomatic, while six (42.9%) reported mild symptoms, primarily cough and nasal congestion. Anti-spike protein IgG levels were approximately 10-fold higher in participants following vaccination compared with participants who had natural infection alone (p < 0.0001) and resembled levels previously reported in the general population. Conclusions: A majority of PwCF have mild or no symptoms of SARS-CoV-2 making it difficult to distinguish from baseline respiratory symptoms. Hispanic PwCF may be disproportionately impacted, consistent with racial and ethnic COVID-19 disparities among the general US population. Vaccination in PwCF generated antibody responses similar to those previously reported in the general population.

Background: Despite the growing awareness of Cystic Fibrosis (CF) in China, few cases have been reported in Henan, which is the most populous province in the country. This study aimed to describe the clinical phenotype and genotype of children with CF in Henan. Methods: We recruited 14 Chinese children with CF who presented to Children’s Hospital affiliated to Zhengzhou University from January 2019 to January 2023. The demographic data, imaging examinations, and laboratory tests of the patients were reviewed to clarify the clinical phenotype. Whole exome sequencing was conducted to identify the genotype. Results: Respiratory diseases were the main clinical manifestation, including recurrent/persistent pneumonia (85.7%), sinusitis (71.4%), bronchiectasis (71.4%). CF-related liver disease (CFLD) and pancreatic insufficiency (PI) were less common (21.4% each). Infant cases had high frequency of pseudo-Bartter Syndrome (80.0%). Chest computed tomography showed bronchiectasis in older children and air trapping in infant cases. The most common pathogens in the airway were Pseudomonas aeruginosa and Staphylococcus aureus (71.4% respectively). Twenty-four different CFTR gene variants were detected, including four novel observations (c.869+3A>T, c.1064C>G[p.Pro355Arg], c.1209+1G>C and c.1925C>G [p.Ser642X]). The most common variant was c.2909G>A (p.Gly970Asp), with a detected rate of 16.7%. Conclusion: Children with CF in Henan had varied clinical phenotypes by age, with respiratory disease being predominant. The most frequent CFTR gene variant was c.2909G>A(p.Gly970Asp). This study is the first and most comprehensive one on the clinical phenotype and genotype of children with CF in Henan, China. We also reported the first CF case of M. abscessus infection in China.

The ancient Greeks took the entertainment of their crowds very seriously and used drama as a way of investigating the world they lived in. The theatrical re-enactment of suffering and grief in front of a large audience was to foster compassion, as well as a cathartic release of emotion that was restorative through a deeply felt interconnection between actors and audience. When our patients encounter tragedy, we are also drawn into their ordeal and experience it first hand. Such it was with Rose.

The respiratory tract antimicrobial defense system is a multilayered defense mechanism that relies upon mucociliary clearance and components of both the innate and adaptive immune systems to protect the lungs from inhaled or aspirated microorganisms. One of these potential pathogens, non-typeable Haemophilus influenzae ( NTHi), adopts several, multifaceted redundant strategies to successfully colonize the lower airways and establish a persistent infection. NTHi can impair mucociliary clearance, express multiple multi-functional adhesins for various cell types within the respiratory tract and evade host defenses by surviving within and between cells, forming biofilms, increasing antigenic drift, secreting proteases and antioxidants, and by host-pathogen cross-talk, impair macrophage and neutrophil function. NTHi is recognized as an important pathogen in several chronic lower respiratory disorders, such as protracted bacterial bronchitis, bronchiectasis, cystic fibrosis and primary ciliary dyskinesia. The persistence of NTHi in human airways, including its capacity to form biofilms, results in chronic infection and inflammation, which can ultimately injure airway wall structures. The complex nature of the molecular pathogenetic mechanisms employed by NTHi is incompletely understood but improved understanding of its pathobiology will be important for developing effective therapies and vaccines, especially given the marked genetic heterogeneity of NTHi and its possession of phase-variable genes. Currently, no vaccine candidates are ready for large phase III clinical trials.

A 5-month-old male baby was brought to the emergency room with a one-day history of respiratory distress, wheezing, vomiting, and high fever. Wheezing had been present since birth but had recently become more frequent and intense, occurring even at rest. The baby was born full-term by cesarean delivery and had a medical history of gallbladder agenesis, secundum atrial septal defect (ASD), and cryptorchidism.

Severe BPD can be associated with clinical and histologic features that are similar to ACD without evidence of FOXF1 genetic disease.  Importantly, lung FOXF1 and TMEM100 gene expression is markedly decreased in severe BPD, suggesting that impaired FOXF1 signaling may contribute to abnormal lung growth and refractory pulmonary hypertension in BPD.

Background International consensus statements on depression and anxiety in adolescents and adults with CF recommend assessment for comorbid substance misuse. However, at CF centers, the frequency and impact of substance misuse have not been well characterized, and best practices for prevention, identification, and evidence-based treatment have not been routinely implemented. Methods Medical records of 148 adults with CF over 3 years were reviewed to determine the prevalence of substance misuse (alcohol or opiates) and its relationship with clinical variables and healthcare utilization. Independent-sample t-test for continuous outcomes and chi-square test for binary outcomes were used to compare groups with and without substance misuse. Results Substance misuse was documented in 28 (19%) adults with CF, equally distributed between alcohol (n=13) and opiates (n=15). Adults with substance misuse were more likely to be male. The prevalence of diagnosed anxiety and depression did not differ significantly between groups, but those with substance misuse had more severe anxiety (GAD-7: 10.0±6.1 vs. 3.3±4.4; p<0.001) and depressive symptoms (PHQ-9: 10.4±6.5 vs. 4.0±4.8; p<0.001). Adults with substance misuse had higher annual rates of missed outpatient CF visits and inpatient hospitalizations, with hospital admissions of longer mean duration. Conclusions In adults with CF, substance misuse is common and is associated with adverse indicators of emotional and physical health and service utilization, suggesting that systematic approaches to addressing substance misuse in CF clinics should be considered. Prospective, longitudinal study is warranted to elucidate the complex relationships between depression, anxiety, substance misuse, and health outcomes in individuals with CF.

Unperceived button battery ingestion in infants may be associated with significant morbidity, especially when medical assistance is restricted.

Cystic fibrosis has seen a multitude of therapeutic advances targeting its downstream effects. This has led to a steady increase in survival over the past few decades. The recent development of disease-modifying drugs targeting the underlying CFTR mutation has revolutionized treatment for CF. Despite these advances, individuals with CF who are racial and ethnic minorities, from low socioeconomic status, or female sex have worse clinical outcomes. The inequitable access to CFTR modulators from cost and/or genetic eligibility has the potential to further worsen the existing health disparities seen within the CF community.

Safety of Biologicals In Severe Asthma Patients Having COVID-19Running title: COVID-19, biologicals and severe asthma