Airway obstruction due to ingestion of sodium polyacrylate: a case report.

BACKGROUND: Super-absorbent polymers (SAPs) possess the ability to absorb large amounts of water and are widely used in medical settings. Commonly used in vomit bags to contain fluids, reduce spillage, and enhance bedside hygiene, SAPs are generally regarded as safe and non-toxic. However, we report a tragic incident where the accidental ingestion of SAPs led to fatal asphyxiation, highlighting a critical safety concern. CASE PRESENTATION: A 76-year-old female suffering from advanced Alzheimer's dementia was brought to the emergency department following a fall with cervical trauma. Following a complaint of nausea, she was given a vomit bag containing a sachet of approximately 9 g of SAP. Thirty minutes later, she was found deceased in the waiting area, with a grayish, half-hardened gel blocking her oropharynx and remnants of a chewed SAP sachet. Pathological analysis confirmed death by asphyxiation caused by the SAP expanding in her oropharynx upon contact with saliva. CONCLUSIONS: This case emphasizes the potential dangers of SAPs when accidentally ingested and it is imperative that such products are kept out of reach of vulnerable populations. In cases of airway obstruction, there are no specific treatments available. Laryngoscopy may be impossible, necessitating the prompt consideration of an emergency tracheotomy. Experimental data suggest the use of an aerosol of warm alkaline hydrogen peroxide solution to dissolve these obstructive foreign bodies, but further studies are needed to validate its use in emergency situations.

Discordant definitions of small airway dysfunction between spirometry and parametric response mapping: the HRCT-based study.

OBJECTIVES: To analyze the lung structure of small airway dysfunction (SAD) defined by spirometry and parametric response mapping (PRM) using high-resolution computed tomography (HRCT), and to analyze the predictive factors for SAD. METHODS: A prospective study was conducted with 388 participants undergoing pulmonary function test (PFT) and inspiratory-expiratory chest CT scans. The clinical data and HRCT assessments of SAD patients defined by both methods were compared. A prediction model for SAD was constructed based on logistic regression. RESULTS: SAD was defined in 122 individuals by spirometry and 158 by PRM. In HRCT visual assessment, emphysema, tree-in-bud sign, and bronchial wall thickening have higher incidence in SAD defined by each method. (p < 0.001). Quantitative CT showed that spirometry-SAD had thicker airway walls (p < 0.001), smaller lumens (p = 0.011), fewer bronchi (p < 0.001), while PRM-SAD had slender blood vessels. Predictive factors for spirometry-SAD were age, male gender, the volume percentage of emphysema in PRM (PRMEmph), tree-in-bud sign, bronchial wall thickening, bronchial count; for PRM-SAD were age, male gender, BMI, tree-in-bud sign, emphysema, the percentage of blood vessel volume with a cross-sectional area less than 1 mm2 (BV1/TBV). The area under curve (AUC) values for the fitted predictive models were 0.855 and 0.808 respectively. CONCLUSIONS: Compared with PRM, SAD defined by spirometry is more closely related to airway morphology, while PRM is sensitive to early pulmonary dysfunction but may be interfered by pulmonary vessels. Models combining patient information and HRCT assessment have good predictive value for SAD. CRITICAL RELEVANCE STATEMENT: HRCT reveals lung structural differences in small airway dysfunction defined by spirometry and parametric response mapping. This insight aids in understanding methodological differences and developing radiological tools for small airways that align with pathophysiology. KEY POINTS: Spirometry-SAD shows thickened airway walls, narrowed lumen, and reduced branch count, which are closely related to airway morphology. PRM shows good sensitivity to early pulmonary dysfunction, although its assessment of SAD based on gas trapping may be affected by the density of pulmonary vessels and other lung structures. Combining patient information and HRCT features, the fitted model has good predictive performance for SAD defined by both spirometry and PRM (AUC values are 0.855 and 0.808, respectively).

Improved Composite Hydrogel for Bioengineered Tracheal Graft Demonstrates Effective Early Angiogenesis.

Background/Objectives: Collagen-agarose hydrogel blends currently used in tracheal graft bioengineering contain relatively high concentrations of collagen to withstand mechanical stresses associated with native trachea function (e.g., breathing). Unfortunately, the high collagen content restricts effective cell infiltration into the hydrogel. In this study, we created an improved hydrogel blend with lower concentrations of collagen (<5 mg/mL) and characterized its capacity for fibroblast invasion and angiogenesis. Methods: Four collagen-agarose hydrogel blends were created: 1 mg/mL type 1 collagen (T1C) and 0.25% agarose, 1 mg/mL T1C and 0.125% agarose, 2 mg/mL T1C and 0.25% agarose, and 2 mg/mL T1C and 0.125% agarose. The hydrogel surface was seeded with fibroblasts, while both endothelial cells and fibroblasts (3:1 ratio) were mixed within the hydrogel matrix. We assessed early angiogenesis by observing fibroblast migration and endothelial cell morphology (elongation and branching) at 7 days. In addition, we performed immunostaining for alpha-smooth muscle actin (aSMA) and explored the gene expression of various angiogenic markers (including vascular endothelial growth factor; VEGF). Results: Gels with lower agarose concentrations (0.125%) with 1 or 2 mg/mL T1C were more effective in allowing early attachment and migration of surface-applied fibroblasts compared to gels with higher (0.25%) agarose concentrations. The low-agarose gels also allowed cells to quickly adopt a spread morphology and self-assemble into elongated structures indicative of early angiogenesis, while demonstrating positive immunostaining for aSMA and increased gene expression of VEGF by day 7. Conclusions: Hydrogel blends with collagen and low agarose concentrations may be effective in allowing early cellular infiltration and angiogenesis, making such gels a suitable cell substrate for use in the development of composite bioengineered tracheal grafts. The collagen-agarose hydrogel blend is meant to be cast around a three-dimensional (3D) printed polycaprolactone support structure and wrapped in porcine small intestine submucosa ECM to create an off-the-shelf bioengineered tracheal implant.

Airway management for patients with tracheal stenosis and severe scar contracture of the face and neck via bronchoscopy: a case report.

Both anaesthesiologists and surgeons experience challenges in managing airway stenosis and scar contracture in the face and neck. Herein, we report the case of a 38-year-old woman (BMI 23.1 kg/m2, third-degree burns covering 40% of her body, an American Society of Anaesthesiologists physical status III) with an unusual case of airway constriction. This patient had a predictable difficult airway (mouth opening of 2 cm, bilateral nostril scar hyperplasia, Mallampatti score III, scarring of the head and neck, and severe tracheal stenosis). Tracheal stenosis measuring 5.5 mm in width as observed 8 cm below the glottis, and the bronchoscope could not pass through it. After two failed attempts at laryngeal mask insertion, we decided to instead insert a custom-made tracheal tube under the guidance of a fiberoptic bronchoscope. The operation was successful, and the patient was transferred to the intensive care unit (ICU).

Robotic-assisted carinal reconstruction using cross-table ventilation.

Carinal reconstruction remains a technically challenging procedure for thoracic surgeons due to the complexity of airway resection and management. This is typically performed in the setting of tumour resection affecting the carina and distal trachea. Airway management of patients undergoing surgical resection of tumours involving the carina is highly challenging. This is due to an open, shared airway and the need for single-lung ventilation to facilitate surgery. Common modalities used for intraoperative ventilation include cross-table ventilation, veno-venous extra-corporeal membrane oxygenation and cardiopulmonary bypass. Cardiopulmonary bypass is usually avoided due to the requirement of full heparinization, which increases the demands of a technically challenging procedure, in addition to its contraindication in oncological resections. Extra-corporeal membrane oxygenation is not readily available in most thoracic units. This leaves cross-table ventilation, which is commonly used for open thoracotomy and sternotomy cases, but has never been reported for minimally invasive procedures.  Specifically, to the best of our knowledge, cross-table ventilation has never been used for minimally invasive robotic carinal reconstruction. We present a step-by-step video tutorial in performing surgical resection of a mediastinal tumour that was found invading the carina. This was performed in a young patient who underwent carinal reconstruction using a novel technique combining cross-table ventilation and robotic-assisted surgery.

May Small Airways Dysfunction (SAD) Play a Role in the Idiopathic Pulmonary Fibrosis (IPF) and May SAD Be a Therapeutic Target?

Small airway dysfunction (SAD) is a pathological process that affects the bronchioles and non-cartilaginous airways below 2 mm in diameter. This short review presents a link between SAD and IPF. Pathomorphological changes of small airways in fibrotic lungs are discussed. Additionally, functional abnormalities related to SAD measured by spirometry and oscillometry are presented. The problem of early detection and treatment of SAD as a procedure potentially capable of mitigating fibrosis is mentioned.

Small Airways Dysfunction and Lung Hyperinflation in Long COVID-19 Patients as Potential Mechanisms of Persistent Dyspnoea.

BACKGROUND: Reticulation, ground glass opacities and post-infection bronchiectasis are present three months following hospitalisation in patients recovering from SARS-CoV-2 infection and are associated with the severity of acute infection. However, scarce data exist on small airways impairment and lung hyperinflation in patients with long COVID-19. AIM: To evaluate small airways function and lung hyperinflation in previously hospitalised patients with long COVID-19 and their association with post-COVID-19 breathlessness. METHODS: In total, 33 patients (mean ± SD, 53 ± 11 years) with long COVID-19 were recruited 149 ± 90 days following hospital discharge. Pulmonary function tests were performed and lung hyperinflation was defined as RV/TLC ≥ 40%. Small airways function was evaluated by measuring the closing volume (CV) and closing capacity (CC) using the single-breath nitrogen washout technique (SBN2W). RESULTS: CC was 115 ± 28% pred. and open capacity (OC) was 90 ± 19. CC was abnormal in 13 patients (39%), CV in 2 patients (6.1%) and OC in 9 patients (27%). Lung hyperinflation was present in 15 patients, whilst the mean mMRC score was 2.2 ± 1.0. Lung hyperinflation was associated with CC (r = 0.772, p = 0.001), OC (r = 0.895, p = 0.001) and mMRC (r = 0.444, p = 0.010). CONCLUSIONS: Long COVID-19 patients present with small airways dysfunction and lung hyperinflation, which is associated with persistent dyspnoea, following hospitalisation.

The Impact of Heat-Not-Burn, E-Cigarettes, and Cigarettes on Small Airway Function.

Introduction: E-cigarettes and heated tobacco products (HTPs) are gaining worldwide significance. The tobacco industry is promoting these products as healthier alternatives to conventional cigarettes. Methods: In this four-arm crossover study, we examined the acute effects of cigarette smoking, vaping IQOS, or vaping e-cigarettes (with or without nicotine) on hemodynamics, arterial stiffness, and small airways. Twenty subjects (10 male, 10 female), all occasional smokers, completed each study arm. There was at least a 48 h washout period before each test day. Arterial stiffness and peripheral and central hemodynamics were assessed using Mobil-O-Graph™ (I.E.M., Germany), whereas tremoFlo® c-100 (Thoracic Medical Systems Inc) was used to evaluate the effects on the small airways and resistance. Results: Cigarettes, IQOS, e-cigarettes containing nicotine, and nicotine-free e-cigarettes had similar effects on peripheral and central hemodynamics as well as on arterial stiffness. We observed a significant increase in all parameters. However, only nicotine-containing products lead to increased bronchial obstruction, higher reactance, and a higher tidal volume. Conclusion: Therefore, we concluded that cigarettes, IQOS, and e-cigarettes have similar effects on hemodynamics. No differences were observed between the nicotine-containing and nicotine-free e-cigarettes. All nicotine-containing products also influence small airways. These findings suggest that e-cigarettes and HTPs are not healthier alternatives than conventional cigarettes.

Airways abnormalities in a prospective cohort of patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) affects roughly 1% of the population and commonly involves the lungs. Of lung involvement in RA, interstitial lung disease (ILD) is well-known; however, airways disease in RA is relatively understudied. RESEARCH QUESTIONS: What are the baseline airways abnormalities in a prospective cohort of patients with RA based on pulmonary function tests (PFT), high-resolution CT scans (HRCT) and computational imaging analysis and are there associations between these abnormalities and respiratory symptoms? STUDY DESIGN AND METHODS: In this single-center study, 188 patients with RA without a clinical diagnosis of ILD underwent HRCT and PFT. Radiologists assessed HRCTs for airway abnormalities. Computational imaging via VIDA Vision software and in-house quantitative CT (qCT) analysis was applied to 147 HRCTs to quantify airway abnormalities. RESULTS: Airways obstruction (FEV1/FVC ratio < 0.7) was present in 20.7% of patients, and associated with older age, male sex and higher smoking rate. Radiologists identified airway abnormalities in 61% of patients-55% had bronchial wall thickening, 12% bronchiectasis, and 5% mosaic attenuation; these airways findings were associated with older age, male sex, lower FEV1, FVC, FEV1/FVC ratios, and higher rates of rheumatoid factor positivity. Prespecified qCT metrics (wall thickening % and emphysema %) correlated with PFT obstruction and more severe respiratory symptoms including shortness of breath and cough. INTERPRETATION: There were high rates of airways abnormalities in this prospective RA cohort based on three methods of detection. There were significant associations between qCT measures and respiratory symptoms. Airways disease may be an under-recognized extra-articular manifestation of RA and qCT may be a sensitive method to detect the clinical impact on respiratory symptoms.

Evaluation of the Effects of Orthopedic Treatment on the Dentofacial Structure and Upper Airway of Subjects with Skeletal Class III Malocclusion.

Objective: The present study aimed to evaluate the effect of rapid maxillary expansion (RME) and face mask treatment on the upper airway in patients with maxillary retrusion in two dimensions using digital cephalograms and volumetric evaluation using acoustic rhinometric measurements. Methods: A total of 22 individuals with a concave profile and skeletal and dental Class III malocclusion during growth and development with a mean age of 9.9±1.38 years were included in the study. A bonded RME appliance and a petit face mask were adapted for the patients. Before treatment (T0) and after maxillary protraction (T1), lateral cephalometric films and acoustic rhinometric recordings were obtained. The dependent sample t-test was used for statistical evaluation. Results: Cephalometric analysis revealed forward movement of the maxilla and backward downward rotation of the mandible. A significant increase was observed in the nasopharyngeal and oropharyngeal regions of the upper airway. Three-dimensional evaluation of the upper airway by acoustic rhinometry revealed only an increase in the volumes of the left nasal cavity after decongestant administration. A statistically significant increase in acoustic rhinometric measurements in nasal valves. When the correlation of the cephalometric findings of the nasopharyngeal region with the acoustic rhinometry findings was examined, no statistically significant relationship was found. Conclusion: As a result of this study, we observed an increase in the cephalometric measurements of the nasopharyngeal and oropharyngeal areas. A significant increase was observed in the minimal cross-sectional area measured by acoustic rhinometry.

Choosing the Right Biologic for the Right Patient With Severe Asthma.

In this instalment of the How I Do It series on severe asthma, we tackle the clinical conundrum of choosing the right biologic for the right patient with severe asthma. With 6 biologics now approved for use in this area comprising 4 different targeting strategies (anti-Ig E: omalizumab; anti-IL-5 and anti-IL-5-receptor: mepolizumab, reslizumab, and benralizumab; anti-IL-4-receptor: dupilumab; anti-thymic stromal lymphopoietin: tezepelumab), this question is increasingly complex. Recognizing that no head-to-head trial has compared biologics, we based our review on the expected effects of inhibiting different aspects of type 2 airway inflammation, supported whenever possible by clinical trial and real-world data. We use 4 variations of a case of severe uncontrolled asthma to develop concepts and considerations introduced in the previous installment ("Workup of Severe Asthma") and discuss pregnancy-related, biomarker-related, comorbidity-related, and corticosteroid dependency-related considerations when choosing a biologic. The related questions of deciding when, why, and how to switch from one biologic to another also are discussed. Overall, we consider that the choice of biologics should be based on the available clinical trial data for the desired efficacy outcomes, the biomarker profile of the patient, safety profiles (eg, when pregnancy is considered), and opportunities to target 2 comorbidities with 1 biologic. Using systemic and airway biomarkers (blood eosinophils and exhaled nitric oxide) and other phenotypic characteristics, we suggest a framework to facilitate therapeutic decision-making. Post hoc studies and new comparative studies are needed urgently to test this framework and to determine whether it allows us to make other clinically useful predictions.

Enhancing Airway Management: A Comparative Study of Macintosh and TAS Scope in Difficult Intubations.

Background: Intubation is essential in anesthesia for patient safety, requiring accurate techniques for difficult airways. Achieving first-attempt success is crucial. This study evaluates traditional laryngoscopes, such as the Macintosh, versus advanced tools like the TAS Scope. Material and Methods: This observational study, conducted from April to August 2023 at Saveetha Medical College and Hospital, involved 60 patients aged 18-65. The two groups of Macintosh laryngoscope and TAS Scope 30 each are based on airway difficulty predictors and patient characteristics. Results: The TAS Scope group had a higher first-attempt success rate and easier intubation experiences according to Likert scale ratings. Conclusion: The study underscores the benefits of using advanced devices like the TAS Scope for difficult airway management, showing higher success rates and ease of use. These findings support the adoption of new technologies to enhance patient safety and intubation effectiveness.

Airway management education and retraining: an unresolved paradigm.

Simulation is a cornerstone of medical education for difficult airway management. The lack of standards regarding the frequency of retraining that would ensure the maintenance of skills and competencies over time still needs to be solved.

The pH-sensitive translocation of V-ATPase in the small airway of cystic fibrosis pigs.

In contrast to pig large airways, the pH of airway surface liquid (ASL) in pig small airways is regulated by CFTR mediated HCO-3 secretion and the vacuolar-type H+ ATPase (V-ATPase) proton secretion. We hypothesized that in Cystic Fibrosis (CF), the ASL pH of small airways is acidic, and the V-ATPase is internalized. We quantified proton secretion during the addition of an alkaline test solutions by measuring changes in a pH dependent fluorescent dye generated by porcine small airway epithelia in the absence and presence of bafilomycin A1. The pH-dependent translocation of V-ATPase in ex vivo and in vivo preparations was measured using immunolocalization of V-ATPase. We found that bafilomycin sensitive proton secretion stopped when the ASL pH was less than 7.10. In non-CF pigs and mice, we found that V-ATPase was localized in the apical membrane, and internalized when the lungs were instilled with a pH 6.8 solution.Studies where we immediately fixed lungs from pigs revealed apical V-ATPase detection in non-CF piglets and less apical detection in CF piglets. Our data suggest that V-ATPase in small airways is internalized when the ASL pH is acidic. The decrease in apical localization of V-ATPase in CF pigs is consistent with an acidic ASL pH.

Anaesthesia Management in a Case of Ludwig's Angina With Difficult Airway Managed by Emergency Tracheostomy.

Severe neck infections present significant challenges for anesthesiologists due to the complexities associated with managing difficult airways. Ludwig's angina, a rapidly progressing infection of the submandibular space, exemplifies these challenges due to the high risk of airway obstruction. This case report details an emergency procedure performed to drain Ludwig's angina, highlighting the difficulties encountered and the strategies employed. Awake fiberoptic intubation is demonstrated as an effective approach for maintaining the airway during such operations. The report underscores the critical nature of quick and effective management, emphasizing the importance of readiness for interventions such as tracheostomy in cases where oxygen saturation drops, thereby ensuring patient safety in precarious situations.

Chest CT Airway and Vascular Measurements in Females with COPD or Long-COVID.

Chest CT provides a way to quantify pulmonary airway and vascular tree measurements. In patients with COPD, CT airway measurement differences in females are concomitant with worse quality-of-life and other outcomes. CT total airway count (TAC), airway lumen area (LA), and wall thickness (WT) also differ in females with long-COVID. Our objective was to evaluate CT airway and pulmonary vascular and quality-of-life measurements in females with COPD as compared to ex-smokers and patients with long-COVID. Chest CT was acquired 3-months post-COVID-19 infection in females with long-COVID for comparison with the same inspiratory CT in female ex-smokers and COPD patients. TAC, LA, WT, and pulmonary vascular measurements were quantified. Linear regression models were adjusted for confounders including age, height, body-mass-index, lung volume, pack-years and asthma diagnosis. Twenty-one females (53 ± 14 years) with long-COVID, 17 female ex-smokers (69 ± 9 years) and 13 female COPD (67 ± 6 years) patients were evaluated. In the absence of differences in quality-of-life scores, females with long-COVID reported significantly different LA (p = 0.006) compared to ex-smokers but not COPD (p = 0.7); WT% was also different compared to COPD (p = 0.009) but not ex-smokers (p = 0.5). In addition, there was significantly greater pulmonary small vessel volume (BV5) in long-COVID as compared to female ex-smokers (p = 0.045) and COPD (p = 0.003) patients and different large (BV10) vessel volume as compared to COPD (p = 0.03). In females with long-COVID and highly abnormal quality-of-life scores, there was CT evidence of airway remodelling, similar to ex-smokers and patients with COPD, but there was no evidence of pulmonary vascular remodelling.Clinical Trial Registration: www.clinicaltrials.gov NCT05014516 and NCT02279329.

Insights into epithelial-mesenchymal transition from cystic fibrosis rat models.

BACKGROUND: Molecular pathways contributing to Cystic Fibrosis pathogenesis remain poorly understood. Epithelial-mesenchymal transition (EMT) has been recently observed in CF lungs and certain CFTR mutation classes may be more susceptible than others. No investigations of EMT processes in CF animal models have been reported. AIM: The aim of this study was to assess the expression of EMT-related markers in Phe508del and knockout (CFTR-KO) rat lung tissue and tracheal-derived basal epithelial stem cells, to determine whether CFTR dysfunction can produce an EMT state. METHOD: The expression of EMT-related markers in lung tissue and cultured tracheal basal epithelial stem cells from wildtype (WT), Phe508del, and CFTR-KO rats were assessed using qPCR and Western blots. Cell responses were evaluated in the presence of Rho-associated protein kinase (ROCK) inhibitor Y27632, which blocks EMT-pathways, or after treatment with TGFß1 to stimulate EMT. RESULTS: Different gene expression profiles were observed between Phe508del and CFTR-KO rat models compared to wild type. There was lower expression of type 1 collagen in KO lungs and primary cell cultures, while Phe508del lungs and cells had higher expression, particularly when treated with TGFß1. The addition of Y27632 rescued changes in EMT related genes in Phe508del cells but not in KO cells. CONCLUSION: Our findings show the first evidence of upregulated EMT pathways in the lungs and airway cells of any CF animal model. Differences in the regulation of the EMT genes and proteins in the Phe508del and CFTR-KO cells suggest that the signalling pathways underlying EMT are CFTR mutation dependent.

Modeling Realistic Geometries in Human Intrathoracic Airways.

Geometrical models of the airways offer a comprehensive perspective on the complex interplay between lung structure and function. Originating from mathematical frameworks, these models have evolved to include detailed lung imagery, a crucial enhancement that aids in the early detection of morphological changes in the airways, which are often the first indicators of diseases. The accurate representation of airway geometry is crucial in research areas such as biomechanical modeling, acoustics, and particle deposition prediction. This review chronicles the evolution of these models, from their inception in the 1960s based on ideal mathematical constructs, to the introduction of advanced imaging techniques like computerized tomography (CT) and, to a lesser degree, magnetic resonance imaging (MRI). The advent of these techniques, coupled with the surge in data processing capabilities, has revolutionized the anatomical modeling of the bronchial tree. The limitations and challenges in both mathematical and image-based modeling are discussed, along with their applications. The foundation of image-based modeling is discussed, and recent segmentation strategies from CT and MRI scans and their clinical implications are also examined. By providing a chronological review of these models, this work offers insights into the evolution and potential future of airway geometry modeling, setting the stage for advancements in diagnosing and treating lung diseases. This review offers a novel perspective by highlighting how advancements in imaging techniques and data processing capabilities have significantly enhanced the accuracy and applicability of airway geometry models in both clinical and research settings. These advancements provide unique opportunities for developing patient-specific models.

Eosinophilic reactive airways disease after immune checkpoint inhibitor treatment.

Immune checkpoint inhibitors (ICI) are increasingly utilized as first-line treatment for many solid tumour malignancies. One downside of ICI therapy is autoimmune-mediated organ inflammation, or immune-related adverse events (irAE). ICI-related pneumonitis, or non-infectious inflammation of the lung, is a well-described irAE. While guidelines surrounding ICI-related pneumonitis are well established, other ICI-related pulmonary toxicities, including reactive airways disease, are rarely described in the literature. Here, we present a series of patients without pre-existing COPD or asthma who developed reactive airways disease with peripheral eosinophilia after ICI therapy and without radiographic evidence of pneumonitis. The patients were treated with typical therapies for reactive airways disease, including- inhaled steroids, bronchodilators, systemic steroids, and in one instance, dupilumab. All experienced symptomatic improvement with these therapies, enabling some of the patients to continue receiving ICI therapy.

Neuroepithelial bodies and terminal bronchioles are niches for distinctive club cells that repair the airways following acute notch inhibition.

Lower airway club cells (CCs) serve the dual roles of a secretory cell and a stem cell. Here, we probe how the CC fate is regulated. We find that, in response to acute perturbation of Notch signaling, CCs adopt distinct fates. Although the vast majority transdifferentiate into multiciliated cells, a "variant" subpopulation (v-CCs), juxtaposed to neuroepithelial bodies (NEBs; 5%-10%) and located at bronchioalveolar duct junctions (>80%), does not. Instead, v-CCs transition into lineage-ambiguous states but can revert to a CC fate upon restoration of Notch signaling and repopulate the airways with CCs and multiciliated cells. The v-CC response to Notch inhibition is dependent on localized activation of ß-catenin in v-CCs. We propose that the CC fate is stabilized by canonical Notch signaling, that airways are susceptible to perturbations to this pathway, and that NEBs/terminal bronchioles comprise niches that modulate CC plasticity via ß-catenin activation to facilitate airway repair post Notch inhibition.