Airway Abnormalities Research Articles

Navigating Diagnostic and Treatment Challenges of Pulmonary Hypertension in Infants with Bronchopulmonary Dysplasia.

Advances in perinatal intensive care have significantly enhanced the survival rates of extremely low gestation-al-age neonates but with continued high rates of bronchopulmonary dysplasia (BPD). Nevertheless, as the survival of these infants improves, there is a growing awareness of associated abnormalities in pulmonary vascular development and hemodynamics within the pulmonary circulation. Premature infants, now born as early as 22 weeks, face heightened risks of adverse development in both pulmonary arterial and venous systems. This risk is compounded by parenchymal and airway abnormalities, as well as factors such as inflammation, fibrosis, and adverse growth trajectory. The presence of pulmonary hypertension in bronchopulmonary dysplasia (BPD-PH) has been linked to an increased mortality and substantial morbidities, including a greater susceptibility to later neurodevelopmental challenges. BPD-PH is now recognized to be a spectrum of disease, with a multifactorial pathophysiology. This review discusses the challenges associated with the identification and management of BPD-PH, both of which are important in minimizing further disease progression and improving cardiopulmonary morbidity in the BPD infant.

Defective mesenchymal Bmpr1a-mediated BMP signaling causes congenital pulmonary cysts.

Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study using genetic mouse models, we dissected the roles of bone morphogenetic protein (BMP) receptor 1a (Bmpr1a)-mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.

Defective mesenchymal Bmpr1a-mediated BMP signaling causes congenital pulmonary cysts

Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study using genetic mouse models, we dissected the roles of bone morphogenetic protein (BMP) receptor 1a (Bmpr1a)-mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.

Pregnancy-Related Disorders and Intrauterine Impaired Lung Development

Various pregnancy-related disorders are known to affect fetal lung development negatively. During pregnancy, chronic nutrition and/or oxygen limitation is known to impede lung maturation and induce airway and lung abnormalities. Structural abnormalities and reduced lung function may be evident immediately after birth, persist, or develop with age. The expansion of the fetal lung, fetal breath movements, fetal lung growth, alveolarization, blood-air barrier, extracellular matrix (ECM), airways, surfactant system, and lung immune function are all affected by nutritional limitations during pregnancy. Gestational hypoxia disrupts fetal lung development, which manifests as morphological and functional pulmonary abnormalities. Additionally, intrauterine growth restriction (IUGR), preeclampsia (PE), exposure to air pollution, and smoking are known to interfere with embryonic lung development. Birth defects, such as bronchopulmonary dysplasia, as well as chronic obstructive pulmonary disease (COPD), can be caused by abnormalities in pregnancy. Adequate nutrition, avoidance of smoking, and watchful monitoring and intervention during pregnancy should be promoted to prevent chronic lung disease of the newborn, child, and adult.

Microscopic Small Airway Abnormalities Identified in Early Idiopathic Pulmonary Fibrosis InVivo Using Endobronchial Optical Coherence Tomography.

Rationale: Idiopathic pulmonary fibrosis (IPF) affects the subpleural lung but is considered to spare small airways. Micro-computed tomography (micro-CT) studies demonstrated small airway reduction in end-stage IPF explanted lungs, raising questions about small airway involvement in early-stage disease. Endobronchial optical coherence tomography (EB-OCT) is a volumetric imaging modality that detects microscopic features from subpleural to proximal airways. Objectives: In this study, EB-OCT was used to evaluate small airways in early IPF and control subjects invivo. Methods: EB-OCT was performed in 12 subjects with IPF and 5 control subjects (matched by age, sex, smoking history, height, and body mass index). Subjects with IPF had early disease with mild restriction (FVC: 83.5% predicted), which was diagnosed per current guidelines and confirmed by surgical biopsy. EB-OCT volumetric imaging was acquired bronchoscopically in multiple, distinct, bilateral lung locations (total: 97 sites). IPF imaging sites were classified by severity into affected (all criteria for usual interstitial pneumonia present) and less affected (some but not all criteria for usual interstitial pneumonia present). Bronchiole count and small airway stereology metrics were measured for each EB-OCT imaging site. Measurements and Main Results: Compared with the number of bronchioles in control subjects (mean = 11.2/cm3; SD = 6.2), there was significant bronchiole reduction in subjects with IPF (42% loss; mean = 6.5/cm3; SD = 3.4; P = 0.0039), including in IPF affected (48% loss; mean: 5.8/cm3; SD: 2.8; P < 0.00001) and IPF less affected (33% loss; mean: 7.5/cm3; SD: 4.1; P = 0.024) sites. Stereology metrics showed that IPF-affected small airways were significantly larger, more distorted, and more irregular than in IPF-less affected sites and control subjects. IPF less affected and control airways were statistically indistinguishable for all stereology parameters (P = 0.36-1.0). Conclusions: EB-OCT demonstrated marked bronchiolar loss in early IPF (between 30% and 50%), even in areas minimally affected by disease, compared with matched control subjects. These findings support small airway disease as a feature of early IPF, providing novel insight into pathogenesis and potential therapeutic targets.

Vandetanib as a prospective anti-inflammatory and anti-contractile agent in asthma.

Background: Vandetanib is a small-molecule tyrosine kinase inhibitor. It exerts its therapeutic effects primarily in a range of lung cancers by inhibiting the vascular endothelial growth factor receptor 2. However, it remains unclear whether vandetanib has therapeutic benefits in other lung diseases, particularly asthma. The present study investigated the pioneering use of vandetanib in the treatment of asthma. Methods: In vivo experiments including establishment of an asthma model, measurement of airway resistance measurement and histological analysis were used primarily to confirm the anticontractile and anti-inflammatory effects of vandetanib, while in vitro experiments, including measurement of muscle tension and whole-cell patch-clamp recording, were used to explore the underlying molecular mechanism. Results: In vivo experiments in an asthmatic mouse model showed that vandetanib could significantly alleviate systemic inflammation and a range of airway pathological changes including hypersensitivity, hypersecretion and remodeling. Subsequent in vitro experiments showed that vandetanib was able to relax the precontracted rings of the mouse trachea via calcium mobilization which was regulated by specific ion channels including VDLCC, NSCC, NCX and K+ channels. Conclusions: Taken together, our study demonstrated that vandetanib has both anticontractile and anti-inflammatory properties in the treatment of asthma, which also suggests the feasibility of using vandetanib in the treatment of asthma by reducing abnormal airway contraction and systemic inflammation.

Post-extubation laryngitis in children: diagnosis, management and follow-up

ObjectivesTo describe the occurrence of post-extubation laryngitis, analyze its one-year evolution, and correlate laryngeal lesions with clinical outcomes. MethodsRetrospective study including children up to 13 years old at a tertiary hospital between March 2020 and March 2022 with diagnosis of post-extubation laryngitis confirmed by endoscopic examination. Exclusion criteria were prior history of intubation or anatomical airway abnormalities. Medical records were reviewed to characterize patients, underlying diagnosis, laryngeal lesions, treatment, and outcomes at 12-month follow-up. ResultsThe study included 38 endoscopically confirmed post-extubation laryngitis cases, corresponding to 86.4% of suspected cases. The mean age was 13.24 months, and 60.5% were male. Acute respiratory failure was the leading cause of intubation. Initial treatment was clinical, and initial diagnosis was defined by nasopharynoglaryngoscopy and/or Microlaryngoscopy and Bronchoscopy (MLB) findings. Initial diagnostic MLB was performed in 65.7% of the patients. Approximately half (53%) of the patients exhibited moderate or severe laryngeal lesions. When compared to mild cases, these patients experienced a higher rate of extubation failures (mean of 1.95 vs. 0.72, p = 0.0013), underwent more endoscopic procedures, and faced worse outcomes, such as the increased need for tracheostomy (p = 0.0001) and the development of laryngeal stenosis (p = 0.0450). Tracheostomy was performed in 14 (36.8%) children. Patients undergoing tracheostomy presented more extubation failures and longer intubation periods. Eight (21%) developed laryngeal stenosis, and 17 (58.6%) had complete resolution on follow-up. ConclusionPost-extubation laryngitis is a frequent diagnosis among patients with clinical symptoms or failed extubation. The severity of laryngeal lesions was linked to a less favorable prognosis observed at one-year follow-up. Otolaryngological evaluation, follow-up protocols, and increased access to therapeutic resources are essential to manage these children properly. Level of evidenceLevel 4.

Micro-CT Imaging of Tracheal Development in Down Syndrome and Non-Down Syndrome Fetuses.

Down syndrome (DS) is associated with airway abnormalities including a narrowed trachea. It is uncertain whether this narrowed trachea in DS is a consequence of deviant fetal development or an acquired disorder following endotracheal intubation after birth. This study aimed to compare the tracheal morphology in DS and non-DS fetuses using microfocus computed tomography (micro-CT). Twenty fetal samples were obtained from the Dutch Fetal Biobank and divided into groups based on gestational age. Micro-CT images were processed to analyze tracheal length, volume, and cross-sectional area (CSA). Mean tracheal length and tracheal volume were similar in DS and non-DS fetuses for all gestational age groups. Mean, minimum, and maximal tracheal CSA were statistically significantly increased in the single DS fetus in the group of 21-24 weeks of gestation, but not in other gestational age groups. In 90% of all studied fetuses, the minimum tracheal CSA was located in the middle third of the trachea. Tracheal development in DS fetuses was similar to non-DS fetuses between 13 and 21 weeks of gestation. This suggests that the narrowed tracheal diameter in DS children may occur later in fetal development or results from postnatal intubation trauma. The narrowest part of the trachea is in majority of DS and non-DS fetuses the middle third. 3 Laryngoscope, 134:4389-4395, 2024.

Clinical features of plastic bronchitis in children after congenital heart surgery

BackgroundPlastic bronchitis (PB) can occur in patients who have undergone congenital heart surgery (CHS). This study aimed to investigate the clinical features of PB in children after CHS.MethodsWe conducted a retrospective cohort study using the electronic medical record system. The study population consisted of children diagnosed with PB after bronchoscopy in the cardiac intensive care unit after CHS from May 2016 to October 2021.ResultsA total of 68 children after CHS were finally included in the study (32 in the airway abnormalities group and 36 in the right ventricular dysfunction group). All children were examined and treated with fiberoptic bronchoscopy. Pathogens were detected in the bronchoalveolar lavage fluid of 41 children, including 32 cases in the airway abnormalities group and 9 cases in the right ventricular dysfunction group. All patients were treated with antibiotics, corticosteroids (intravenous or oral), and budesonide inhalation suspension. Children with right ventricular dysfunction underwent pharmacological treatment such as reducing pulmonary arterial pressure. Clinical symptoms improved in 64 children, two of whom were treated with veno-arterial extracorporeal membrane oxygenation (ECMO) due to recurrent PB and disease progression.ConclusionsChildren with airway abnormalities or right ventricular dysfunction after CHS should be alerted to the development of PB. Pharmacological treatment such as anti-infection, corticosteroids, or improvement of right ventricular function is the basis of PB treatment, while fiberoptic bronchoscopy is an essential tool for the diagnosis and treatment of PB. ECMO assistance is a vital salvage treatment for recurrent critically ill PB patients.

Revisiting airway epithelial dysfunction and mechanisms in chronic obstructive pulmonary disease: Role of mitochondrial damage.

Chronic exposure to environmental hazards causes airway epithelial dysfunction, primarily impaired physical barriers, immune dysfunction, and repair or regeneration. Impairment of airway epithelial function subsequently leads to exaggerated airway inflammation and remodeling, the main features of chronic obstructive pulmonary disease (COPD). Mitochondrial damage has been identified as one of the mechanisms of airway abnormalities in COPD, which is closely related to airway inflammation and airflow limitation. In this review, we evaluate updated evidence for airway epithelial mitochondrial damage in COPD and focus on the role of mitochondrial damage in airway epithelial dysfunction. In addition, the possible mechanism of airway epithelial dysfunction mediated by mitochondrial damage is discussed in detail, and recent strategies related to airway epithelial-targeted mitochondrial therapy are summarized. Results have shown that dysregulation of mitochondrial quality and oxidative stress may lead to airway epithelial dysfunction in COPD. This may result from mitochondrial damage as a central organelle mediating abnormalities in cellular metabolism. Mitochondrial damage mediates pro-cellular senescence effects due to mitochondrial reactive oxygen species, which effectively exacerbate different types of programmed cell death, participate in lipid metabolism abnormalities, and ultimately promote airway epithelial dysfunction and trigger COPD airway abnormalities. These can be prevented by targeting mitochondrial damage factors and mitochondrial transfer. Thus, because mitochondrial damage is involved in COPD progression as a central factor of homeostatic imbalance in airway epithelial cells, it may be a novel target for therapeutic intervention to restore airway epithelial integrity and function in COPD.

Pulmonary function assessments and clinical correlates in children with sickle cell disease in Cape Town, South Africa

Objectives: Among children with sickle cell disease (SCD) in Africa, there are varied reports on pulmonary function assessments. Restrictive pulmonary function is common in children with SCD in Africa; however, reports from Africa are few. We aimed to describe pulmonary function and its clinical correlates in children with SCD in Cape Town, South Africa. Materials and Methods: A prospective cross-sectional study was carried out over seven months from October 2018 to April 2019 in children 6–16 years with SCD. Children with hemoglobin (Hb) genotypes, homozygous for the BS globin mutation, and sickle-beta0-thalassemia Hb were included in the study. Children were excluded if they had acute complications. Medical record review clinical, laboratory, and pulmonary function assessments were done. Data were entered into Excel and exported to Stata Version 16.0 statistical software for analysis. Results: A total of 25 participants were recruited, mean (standard deviation) age of 10 ± (3.0) years. Thirteen (53%) children were under ten years and 15 (60%) were male. The median/interquartile range age at diagnosis was 1.7 [0.8–3.0] years. SCD-related complications were common. A review of the medical records showed a third of the patients (32%) had at least one previous episode of acute chest syndrome, 20 (80%) had a history of vaso-occlusive crisis, and 15 (76%) had required at least one blood transfusion. Spirometry was performed on 19 (76%) of the participants 9 (47%) had abnormal lung function. The most common spirometry abnormality was a restrictive pattern (forced vital capacity (FVC) &lt; lower limit of normal (LLN)). No participant had a positive bronchodilator response. Older age was associated with a decrease in forced expiratory volume in the first second (FEV1) Z-score (−0.16, 95% confidence interval [CI] −0.31, −0.01; P = 0.04). Children on hydroxyurea similarly had reduced FEV1 Z-score (−1.5, 95%CI −2.88, −0.12; P = 0.04) and reduced FVC Z-score (−2.21, 95%CI −3.64, −0.79; P &lt; 0.001). Conclusion: Lung function abnormalities were common among children with SCD, with restrictive abnormality predominating. Asthma and obstructive airway abnormalities were uncommon in children with SCD in South Africa.

Prognostic Risks for Tracheostomy in Pierre Robin Sequence: A Cohort From a Tertiary Hospital in Thailand.

Pierre Robin sequence (PRS), characterized by micrognathia, glossoptosis, cleft palate, and obstructed airways, is one of the craniofacial conditions challenging various approaches to managing compromised airways, ranging from conservative measures to invasive airway surgery. This study was conducted to identify predictive risk factors for tracheostomy in the PRS. A retrospective chart review was conducted at a tertiary referral hospital in Thailand. Children diagnosed with PRS from January 2010 to December 2021 were enrolled. Univariate and multivariate analysis methods were used to identify the risk factors. Sixty-five patients with PRS were identified in electronic medical records, but 6 were excluded. Thirteen of the remaining 59 patients underwent tracheostomy. There were no significant differences in sex, preterm gestational age, cleft palate, associated syndromes, chromosome abnormalities, or cardiac or neurological involvement between patients who received tracheostomy and those who did not. However, patients with oropharyngeal dysfunction who received tracheostomy tended to use a nasogastric tube or percutaneous gastrostomy 92.3% of the time ( P = 0.043). In addition, patients with abnormal airways from endoscopy were more likely to undergo tracheostomy (odds ratio, 2.17; 95% confidence interval [CI], 1.20-3.90). Interestingly, patients with a sum of Apgar scores at 1 and 5 minutes <15 were more likely to undergo tracheostomy (adjusted odds ratio, 9.91; 95% CI, 1.32-74.52). Furthermore, patients with at least 3 identified comorbidities were more likely to undergo tracheostomy (adjusted odds ratio, 11.34; 95% CI, 1.16-111.15). The need for tracheostomy depends on comorbidities, Apgar scores, and abnormal airway anatomy. Feeding methods can become more complex with tracheostomy. Prognostic risk factors can help guide treatment and counseling for health care workers and caregivers.

Quercetin improves epithelial regeneration from airway basal cells of COPD patients.

Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced expression of several genes involved in epithelial repair. Quercetin reduces airway epithelial remodeling and inflammation in COPD models, therefore we examined whether quercetin promotes normal epithelial regeneration from COPD BC by altering gene expression. COPD BC treated with DMSO or 1 µM quercetin for three days were cultured at air/liquid interface (ALI) for up to 4 weeks. BC from healthy donors cultured at ALI were used as controls. Polarization of cells was determined at 8 days of ALI. The cell types and IL-8 expression in differentiated cell cultures were quantified by flow cytometry and ELISA respectively. Microarray analysis was conducted on DMSO or 1 µM quercetin-treated COPD BC for 3 days to identify differentially regulated genes (DEG). Bronchial brushings obtained from COPD patients with similar age and disease status treated with either placebo (4 subjects) or 2000mg/day quercetin (7 subjects) for 6 months were used to confirm the effects of quercetin on gene expression. Compared to placebo-, quercetin-treated COPD BC showed significantly increased transepithelial resistance, more ciliated cells, fewer goblet cells, and lower IL-8. Quercetin upregulated genes associated with tissue and epithelial development and differentiation in COPD BC. COPD patients treated with quercetin, but not placebo showed increased expression of two developmental genes HOXB2 and ELF3, which were also increased in quercetin-treated COPD BC with FDR < 0.001. Active smokers showed increased mRNA expression of TGF-β (0.067) and IL-8 (22.0), which was reduced by 3.6 and 4.14 fold respectively after quercetin treatment. These results indicate that quercetin may improve airway epithelial regeneration by increasing the expression of genes involved in epithelial development/differentiation in COPD. This study was registered at ClinicalTrials.gov on 6-18-2019. The study number is NCT03989271.

Identification of abnormal airway niches in the fibrotic lung using spatial transcriptomics

Identification of abnormal airway niches in the fibrotic lung using spatial transcriptomics

Flexible bronchoscopy insufflated and high-flow nasal oxygen pilot trial (BUFFALO protocol pilot trial)

BackgroundHypoxaemia occurs in approximately 30% of children during anaesthesia for flexible bronchoscopy. High-flow nasal oxygen (HFNO) can prolong safe apnoea time and be used in children with abnormal airways. During flexible bronchoscopy, there is limited evidence if HFNO confers advantages over current standard practice in avoiding hypoxaemia. The aim is to investigate feasibility of HFNO use during anaesthesia for flexible bronchoscopy to reduce frequency of rescue oxygenation and hypoxaemia.MethodsBUFFALO is a bi-centre, unmasked, randomised controlled, parallel group, protocol for a pilot trial comparing HFNO techniques to standard practice during anaesthesia. Children (n = 81) aged > 37 weeks to 16 years presenting for elective bronchoscopy who fulfil inclusion but not exclusion criteria will be randomised prior to the procedure to HFNO or standard care oxygenation post induction of anaesthesia. Maintenance of anaesthesia with HFNO requires total venous anaesthesia (TIVA) and with standard, either inhalational or TIVA at discretion of anaesthetist in charge of the patient. Outcomes will include the feasibility of recruitment and adherence to trial procedures, acceptability of the intervention of the protocol and completion rates of data collection methods.DiscussionFindings of this trial will determine feasibility to plan for a larger multicentre randomised clinical trial and support the feasibility of the proposed study procedures.Trial registrationBUFFALO trial was registered with Australia and New Zealand Clinical Trials Registry (TRN12621001635853) on 29 November 2021 and commenced recruitment in May 2022. https://www.anzctr.org.au/. The primary manuscript will be submitted for publication in a peer-reviewed journal.

Airway and Anaesthetic Management of Adult Patients with Mucopolysaccharidoses Undergoing Cardiac Surgery.

Background: Mucopolysaccharidoses (MPSs) are rare congenital lysosomal storage disorders due to a deficiency of enzymes metabolising glycosaminoglycans, leading to their accumulation in tissues. This multisystem disease often requires surgical intervention, including valvular cardiac surgery. Adult MPSs have complex airways making anaesthesia risky. Methods: We report novel three-dimensional (3D) modelling airway assessments and multidisciplinary peri-operative airway management. Results: Five MPS adults underwent cardiac surgery at the national MPS cardiac centre (type I = 4, type II = 1; ages 20, 24, 33, 35, 37 years; two males, three females). All had complex airway abnormalities. Assessments involved examination, nasendoscopy, imaging, functional studies, 3D reconstruction, virtual endoscopy, virtual reality and simulation using computerised, physical modelling. Awake oral fibre-optic intubation was achieved via airway conduit. Staged extubation was performed on the first post-operative day under laryngo-tracheoscopic guidance. The post-operative period involved chest physiotherapy and occupational therapy. All patients had safe intubation, ventilation and extubation. Four had good cardiac surgical outcomes, one (MPS type I; age 35 years) was inoperable due to endocarditis. None had post-operative airway complications. Conclusions: Expertise from cardiovascular-heart team, multidisciplinary airway management, use of novel techniques is vital. Traditional airway assessments are insufficient, so ENT input, radiology and computerised methods to assess and simulate the airway in 3D by collaboration with clinical engineering is essential.

Repetitive sulfur dioxide exposure in mice models post-deployment respiratory syndrome.

Soldiers deployed to Iraq and Afghanistan have a higher prevalence of respiratory symptoms than nondeployed military personnel and some have been shown to have a constellation of findings on lung biopsy termed post-deployment respiratory syndrome (PDRS). Since many of the subjects in this cohort reported exposure to sulfur dioxide (SO2), we developed a model of repetitive exposure to SO2 in mice that phenocopies many aspects of PDRS, including adaptive immune activation, airway wall remodeling, and pulmonary vascular (PV) disease. Although abnormalities in small airways were not sufficient to alter lung mechanics, PV remodeling resulted in the development of pulmonary hypertension and reduced exercise tolerance in SO2-exposed mice. SO2 exposure led to increased formation of isolevuglandins (isoLGs) adducts and superoxide dismutase 2 (SOD2) acetylation in endothelial cells, which were attenuated by treatment with the isoLG scavenger 2-hydroxybenzylamine acetate (2-HOBA). In addition, 2-HOBA treatment or Siruin-3 overexpression in a transgenic mouse model prevented vascular remodeling following SO2 exposure. In summary, our results indicate that repetitive SO2 exposure recapitulates many aspects of PDRS and that oxidative stress appears to mediate PV remodeling in this model. Together, these findings provide new insights regarding the critical mechanisms underlying PDRS.NEW & NOTEWORTHY We developed a mice model of "post-deployment respiratory syndrome" (PDRS), a condition in Veterans with unexplained exertional dyspnea. Our model successfully recapitulates many of the pathological and physiological features of the syndrome, revealing involvement of the ROS-isoLGs-Sirt3-SOD2 pathway in pulmonary vasculature pathology. Our study provides additional knowledge about effects and long-term consequences of sulfur dioxide exposure on the respiratory system, serving as a valuable tool for future PDRS research.

Tracheobronchial abnormalities on computed tomography angiography in children with congenital heart disease.

To evaluate the assortment of tracheobronchial abnormalities on computed tomography angiography (CTA) in children with congenital heart disease (CHD). In this study approved by the Institute ethics committee, CTA studies of 182 children (age range: 2 days-8 years) with CHD, performed from July 2021 to March 2023 were analyzed. Two pediatric radiologists independently assessed the tracheobronchial airways (from the trachea to lobar bronchi) for developmental and branching anomalies and airway compromise (narrowing). In cases which demonstrated airway compromise, the extent and the cause of airway narrowing were evaluated, and the etiology were divided into extrinsic and intrinsic causes. Interobserver agreement between the two radiologists was calculated using kappa statistics. One hundred children demonstrated normal airway anatomy and no luminal narrowing. Airway narrowing was observed in 63 (34.6%) children (κ: 0.954), and developmental airway anomalies were seen in 32 (17.5%) children (κ: 0.935). Of the 63 children with airway narrowing, 47 (25.8%) children had extrinsic cause for narrowing, 11 (6%) children had intrinsic causes for narrowing, and 5 (2.7%) children had both intrinsic and extrinsic causes attributing to airway compromise. Significant airway narrowing (>50% reduction) was seen in 35 (19.2%) children (κ: 0.945). Tracheobronchial airway abnormalities are frequently associated in children with CHD and need to be appraised preoperatively. Cross-sectional imaging with CTA provides excellent information on tracheobronchial airway anatomy and caliber as well as delineates the possible etiology of airway narrowing, thus accurately diagnosing airway anomalies.

Impact of Lung Function on Asthma Exacerbation Rates in Children Treated with Dupilumab: The VOYAGE Study.

Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab. This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). Endpoints were the proportion of patients achieving clinically meaningful improvements (≥5% or ≥10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV1) by Week 12, annualized severe asthma exacerbation rates from Week 12-52, and mean change from baseline in ppFEV1 to Week 12. At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of children receiving placebo showed improvements of ≥5% in ppFEV1; 106/236 (45%) children receiving dupilumab and 36/114 (32%) receiving placebo achieved improvements in ppFEV1 ≥10%. During the Week 12-52 treatment period, dupilumab vs placebo significantly reduced severe exacerbation rates in all subgroups by 52-60% (all P<0.05). Dupilumab treatment resulted in rapid and sustained improvements in ppFEV1 (Week 12 least squares mean difference [95% CI] vs placebo: 3.54 [0.30, 6.78] percentage points; P=0.03) in children who achieved improvements of ≥5%. Dupilumab vs placebo significantly improved pre-bronchodilator ppFEV1, with a higher proportion of patients achieving a clinically meaningful response at Week 12. Dupilumab also significantly reduced severe exacerbation rates, independent of pre-bronchodilator ppFEV1 response at Week 12. NCT02948959.

Sequence of Events Which Led to Significant Hypoxemia in a Patient with Marfanoid Features Undergoing Elective Cesarean Section Under General Anaesthesia: A Case Report

The airway and respiratory system abnormalities seen in Marfan syndrome pose a significant challenge to the anaesthetist. Here, we discuss the chain of events that occurred during the induction of a primi mother, with Marfanoid features complicated with low platelet count and anaemia due to bone marrow hypoplasia. We then discuss the concerns of Marfan Syndrome and its features concerning anaesthetic management.