Major Airway Research Articles

The expanding role of endobronchial ultrasound in patients with centrally located intrapulmonary tumors

ObjectivesTissue acquisition of lung tumors is crucial for diagnostic and treatment purposes. In patients with centrally located lung tumors without endobronchial abnormalities the yield of conventional bronchoscopy is poor. Objective of this study was to assess diagnostic yield of EBUS-TBNA in patients with lung tumors, located near or adjacent to the major airways. MethodsInternational multicenter retrospective analysis (2013–2018) of linear EBUS databases in Bologna, Italy and Amsterdam, The Netherlands. Patients with a centrally-located lung tumor without endobronchial abnormalities who underwent lung tumor search with linear EBUS were included. Diagnostic yield, feasibility of EBUS guided tumor sampling, complication rate, adequacy of the aspirates for mutational analysis, and assessment of mediastinal/vascular invasion (T4) were evaluated. Results and conclusionReal-time EBUS-TBNA diagnostic yield to sample centrally located intrapulmonary tumor was 83% (136/163) and it was independent of tumor location (paratracheal, mainstem, lobar, segmental bronchus). The feasibility to sample the lung tumor was 89% (145/163). In 4 cases the tumor was not found with EBUS. In the other 14 cases, tumor sampling was not performed due to: loss of the echo window after needle insertion [n = 3], interposition of a large vessel [n = 7], switch to radial EBUS [n = 1], switch and sampling through EUS or EUS-B [n = 3]. No major complications occurred. Mutational analysis was successful in 54/63 (86%) of samples. Using surgery as reference standard, EBUS proved more reliable than CT (24/24, 100% versus 22/24, 91.7%, respectively) in the assessment of mediastinal/vascular tumor invasion (T4 status). In conclusion: Lung tumors presenting without endobronchial abnormalities and located adjacent to the major airways can be safely sampled by EBUS-TBNA resulting in high diagnostic yield irrespective of tumor location. Successful molecular profiling and reliable assessment of mediastinal/vascular invasion (T4) in patients with advanced disease provide additional value to EBUS procedures in the setting of centrally-located lung lesions.

NOD-like receptor family, pyrin domain containing 3 (NLRP3) contributes to inflammation, pyroptosis, and mucin production in human airway epithelium on rhinovirus infection

The airway epithelium maintains mucosal homeostasis and effectively responds to pathogens. The roles of the epithelial NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in human rhinovirus (hRV) infection and its effects mediating epithelial functional changes remain poorly understood. We investigated the mechanisms and cellular functions mediated by the epithelial NLRP3 inflammasome on hRV infection. Using models of primary human nasal epithelial progenitor cells and differentiated human nasal epithelial cells (hNECs) infected by hRV, we functionally examined key factors for NLRP3 inflammasome activation, cell death, and mucus production. Furthermore, NLRP3 and IL-1β in human epithelium from nasal mucosal inflammation induced by hRV were evaluated. The inflammasome-mediated IL-1β secretion and pyroptosis in human nasal epithelial progenitor cells and hNECs on hRV infection were dependent on the DDX33/DDX58-NLRP3-caspase-1-GSDMD axis. In differentiated hNECs hRV could also promote major airway epithelial mucin (MUC5AC) production through this axis. Our results further confirmed that the NLRP3 inflammasome signaling pathway was responsible for suppressing hRV replication in airway epithelium. Finally, hRV infection in chronically inflamed nasal mucosa was associated with epithelial mucus hyperproduction, whereas NLRP3 and IL-1β expression levels were significantly increased in hRV-infected epithelium with goblet cell hyperplasia compared with normal epithelium without viral infection. The current study showed that the NLRP3 inflammasome signaling axis could functionally mediate hRV-induced inflammation, pyroptosis, and mucus production in airway epithelium, which might be an essential mechanism associated with hRV-induced airway remodeling.

A method for determination of tracheobronchial airway geometries from four different strains of mice

Accurate lung morphometry is fundamental for predicting aerosol dosimetry. Currently, lung morphometry is only available for 2–3 species of mice (B6C3F1, BALB/c, and A/J). Based upon in‐situ prepared silicone rubber mouse lung casts, a complete process, including their micro‐CT scanning, segmentation, and automated algorithmic processing enabling the determination of airways geometries was developed for four strains of mice (BALB/c, A/J, ApoE−/− and C57BL/6).Silicone rubber lung casts were prepared in‐situ from 20 ApoE−/− and C57BL/6 mice. The cured mouse lung casts were manually inspected for casting quality and manual morphometry measurements were performed (tracheobronchial generations 1–6) on selected lung casts prior to high resolution micro‐CT scanning. Micro‐CT scanning of existing in‐situ lung casts from BALB/c and A/J mice were also performed. Micro‐CT Images were then segmented to reconstruct a 3D model of the individual lung casts. A skeleton of each processed lung cast was automatically created by shrinking the 3D model of each airway to its centerline. Algorithms were developed for automatic detection of possible skeleton exceptions like closed loops, trifurcations and isolated nodes to be subsequently manually resolved. Finally, the skeleton was automatically measured extracting major airway morphometry characteristics (e.g. airway generation number, length, diameter, bifurcations angles, and angle to gravity).The automated measurement procedure was tested/verified by comparing its measurements of airway length, diameter and bifurcation angles with previous manual morphometry measurements from lung casts of identical BALB/c & A/J mice and the automated measurements of lung casts of two BALB/c mice. Not surprisingly, tracheobronchial airway diameters for ApoE−/− and C57BL/6 mice were similar, but were significantly different from the other murine strains examined. It is anticipated that these anatomical differences will result in different aerosol deposition as predicted by various dosimetry codes (NCRP, ICRP, and Multiple‐Path Particle Dosimetry Model).Support or Funding InformationPMI R&D, Philip Morris Products S.A., Neuchâtel, Switzerland PMI Research Laboratories Pte. Ltd., Singapore Altria Client Services LLC, Richmond, USASynopsys, Exeter, United KingdomThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Endobronchial high-intensity ultrasound for thermal therapy of pulmonary malignancies: simulations with patient-specific lung models

Objective: This study investigates the feasibility of endobronchial ultrasound applicators for thermal ablation of lung tumors using acoustic and biothermal simulations.Methods: Endobronchial ultrasound applicators with planar (10 mm width) or tubular transducers (6 mm outer diameter (OD)) encapsulated by expandable coupling balloons (10 mm OD) are considered for treating tumors from within major airways; smaller catheter-based applicators with tubular transducers (1.7–4 mm OD) and coupling balloons (2.5–5 mm OD) are considered within deep lung airways. Parametric studies were applied to evaluate transducer configurations, tumor size and location, effects of acoustic reflection and absorption at tumor-lung parenchyma interfaces, and the utility of lung flooding for enhancing accessibility. Patient-specific anatomical lung models, with various geometries and locations of tumors, were developed for further evaluation of device performance and treatment strategies. Temperature and thermal dose distributions were calculated and reported.Results: Large endobronchial applicators with planar or tubular transducers (3–7 MHz, 5 min) can thermally ablate tumors attached to major bronchi at up to 3 cm depth, where reflection and attenuation of normal lung localize tumor heating; with lung flooding, endobronchial applicators can ablate ∼2 cm diameter tumors with up to ∼2 cm separation from the bronchial wall, without significant heating of intervening tissue. Smaller catheter-based tubular applicators can ablate tumors up to 2–3 cm in diameter from deep lung airways (5–9 MHz, 5 min).Conclusion: Simulations demonstrate the feasibility of endobronchial ultrasound applicators to deliver thermal coagulation of 2–3 cm diameter tumors adjacent to or accessible from major and deep lung airways.

Prevention and Management of Respiratory Diseases Including Lung Cancer Through Exercise Interventions

The objective of the paper is to create awareness among people about alternative and complimentary methods to protect themselves from respiratory diseases like asthma, bronchitis, chronic obstructive lung disease, cancer etc. The following changes take place in airways as a result of Lung diseases 1) Inflammation: Is a physiological process and plays the role of immunological defense against infection, injury or allergy 2) Hyper secretion of mucus: is a major pathological feature of Airway diseases. It is the result of goblet cell hyperplasia in respiratory mucosa and is a prominent feature of inflammation. Acute inflammation is a defense process and where as Chronic inflammation is a disease process. Chronic Inflammation and mucus hyper secretion are a potential risk factors for an accelerated loss of lung function. It is a common feature in elderly.. The thick viscous mucus in the Lungs will be conducive to pathogens. Continued inflammation and mucus hyper Secretion may significantly contribute to transformation of normal cells into cancer cells ( often as a result of chemical , viral or radioactive damage to genes) 3) Broncospasm: is an additional factor in asthma patients. The three factors together cause breathlessness.

ENDOBRONCHIAL METASTASIS FROM OSTEOSARCOMA

SESSION TITLE: Disorders of the Pleura SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/09/2018 01:15 pm - 02:15 pm INTRODUCTION: Lung is the most frequent site for metastasis from osteosarcoma. Usually, the presentation is with well-defined parenchymal nodules, and unusually with pleural deposits, calcification, or mediastinal nodes. Metastases from osteosarcoma presenting as an isolated endobronchial lesion is discretely rare. CASE PRESENTATION: 36 Y/O man with a diagnosis of osteosarcoma presented with dry cough. The patient CT chest showed a left lower lobe mass with central calcification (figure). The patient underwent bronchoscopy for evaluation left lower lobe mass. The bronchoscopy showed left lower lobe superior segment endobronchial lesion. Hot snare and cryo probe used to debulck the endo bronchial lesion (figure). The lesion was extending deep in the airway and EBUS confirmed the depth of the lesion with the finding for central calcification (figure). Pathology confirmed the diagnosis of metastatic small cell osteosarcoma (figure). DISCUSSION: Airway metastasis of tumors usually rare. The incidence of such metastasis is estimated to be approximately 2%; the most common primary malignancies being renal cell, colorectal, cervical, breast carcinoma, and malignant melanoma.This case presenting an extension of small cell small cell Osteosarcom mass in the left lower lobe into the airway confirmed with EBUS. CONCLUSIONS: Airway inspection is an important test for patient with metastatic tumors to the lung close to a major airways. This will give the chance for a baseline evaluation of the airway for any future progress of disease or future complication of the disease such as hemoptysis. Inexplicable pulmonary manifestations should prompt an early evaluation including bronchoscopy and early institution of local therapy for possible palliation. Reference #1: Mogulkoc N, Goker E, Atasever A, et al. Endobronchial metastasis from osteosarcoma of bone: treatment with intraluminal radiotherapy. Chest. 1999;116:1811–1814 Reference #2: Rubio ER, Chang EE, David O, et al. Pulmonary osteosarcoma: endoscopic management. J Bronchol. 2001;8:277–281 DISCLOSURES: No relevant relationships by Abdul Hamid Alraiyes, source=Web Response No relevant relationships by Mohamed Elrifai, source=Web Response No relevant relationships by Arun Kadamkulam Syriac, source=Web Response

Evaluation of Noncystic Fibrosis Bronchiectasis Using Clinical and Radiological Scorings in Children.

The aim of this study was to evaluate radiological, clinical, and demographic data of patients with noncystic fibrosis bronchiectasis and to compare high-resolution computed tomography (HRCT) scores based on the demographic and clinical characteristics. A total of 34 patients (18 male, 16 female) were assessed in terms of age at symptom onset, age at diagnosis, annual attack frequency, cough severity score, physical examination findings, and pulmonary function test results. Modified Bhalla scoring system (B total) and anatomical prevalence degree score (D total) were used for HRCT examination. There was a strong negative correlation between forced expiratory volume at first second (FEV1) and bronchial dilatation degree (SBRDIL). There was a moderate negative correlation of FEV1, forced vital capacity (FVC), and maximum mid-expiratory flow rate (MEF; 25-75) with bronchiectasis degree (EXBRNC), bronchial wall thickness degree (SBWTHICK), and mucus accumulation in the major airways (PMPLA). The B total, D total, EXBRNC, and SBRDIL scores were significantly higher in patients with hemoptysis and sputum. In comparing B and D total scoring systems, B total provided better results in terms of rale, annual exacerbation frequency (AEF), cough severity score (CSS), and FEV1 values. As it is proved using HRCT, pulmonary function impairment, sputum production, hemoptysis, and increase in AEF strongly correlating with objective HRCT scoring can be accepted as markers for pathological changes due to bronchiectasis.

Predictors of Obtaining Polysomnography Among Otolaryngologists Prior to Adenotonsillectomy for Childhood Sleep-Disordered Breathing.

(1) To assess the predictors for obtaining polysomnography (PSG) in children undergoing adenotonsillectomy (AT) for sleep-disordered breathing, and (2) to estimate the adherence to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guideline recommendations for pre-AT PSG. This was a retrospective cohort study of children who were seen in the Pediatric Otolaryngology Clinic and underwent AT for sleep-disordered breathing over a 13-month period at a single tertiary care children's hospital. Patients with and without pre-AT PSG were compared using bivariate and logistic regression analysis to identify predictors for PSG. Electronic medical records were reviewed for demographic variables, medical comorbidities, and PSG data. Adherence to AAO-HNS guideline recommendations was estimated by calculating the proportion of patients who had a PSG among those who met the recommended criteria for pre-AT PSG. Mean age was 6.6 ± 3.6 years with 53% male. A total of 65 of 324 children (20%) underwent PSG prior to AT. The only factor significantly associated with pre-AT PSG was age 1 to 3 years (odds ratio 4.5, 95% confidence interval [2.2, 9.0], P < .001). Among patients who met AAO-HNS criteria for pre-AT PSG, 28 of 128 (20%) underwent PSG compared to 35 of 186 (19%) who did not meet criteria (odds ratio 1.0, 95% confidence interval [0.6, 1.9], P = .87). Among children who underwent AT, the only significant predictor of obtaining pre-AT PSG was age 1 to 3 years. The rate of adherence to the AAO-HNS guideline recommendations was low (20%), which represents an educational opportunity.

Partial Sleeve Lobectomy Preserving the Upper Lobe Bronchial Artery in Left Lower Lobe Lung Cancer

Bronchial sleeve resections are performed in lung malignancies involving major airways. Key to smooth healing of the anastomosis is an optimal vascularization. Many techniques have been proposed for anastomosis protection and revascularization; the preservation of the bronchial artery has not been considered, however. We present a modification of a partial sleeve left lower lobe resection in which we preserve the left upper bronchus artery by leaving the dorsal wall between the main and the left upper lobe bronchus intact, thus maintaining a physiologic vascularization to the anastomosis.

Inherited pulmonary cylindromas: extending the phenotype of CYLD mutation carriers.

SummaryBackgroundGermline mutations in the tumour suppressor gene CYLD are recognized to be associated with the development of multiple cutaneous cylindromas. We encountered such a patient who presented with breathlessness because of multiple pulmonary cylindromas.ObjectivesTo search for clinical and radiological features of multiple pulmonary cylindromas in a cohort of 16 patients with CYLD mutations.MethodsA retrospective case‐note review was carried out in a tertiary dermatogenetics clinic where CYLD mutation carriers are reviewed on an annual basis. In‐depth investigation was carried out for patients with pulmonary tumours.ResultsFour patients had radiological imaging of their lungs, of which two had multiple pulmonary cylindromas that were confirmed histologically. Serial computed tomography monitoring allowed for pre‐emptive endobronchial laser ablation, preventing major airway obstruction and pulmonary collapse.ConclusionsPulmonary cylindromas are an unrecognized, but infrequently symptomatic, aspect of the phenotype in these patients that can have implications for patient care. They should be considered in patients with a high tumour burden that present with respiratory symptoms, and where appropriate, monitored with serial imaging.

CHARACTERIZATION AND RISK FACTOR IDENTIFICATION IN CHILDREN WITH SEVERE CROUP

Abstract BACKGROUND Croup is a self-limiting illness predominantly affecting young children, the most common etiology being Parainfluenza virus types 1 and 2. While the majority of croup remains self-limiting, 1.6–3% of cases are severe requiring acute airway management such as intubation and ventilatory support. While much is known about the diagnosis, management, and clinical course of self-limiting croup, factors contributing to severe cases remain unexplored. OBJECTIVES To characterize the clinical features and risk factors associated with severe croup in children admitted to a tertiary care centre. DESIGN/METHODS A retrospective chart review study of paediatric patients with severe croup presenting at a single tertiary care paediatric institution between 2011 and 2015 was performed. Severe croup was defined as those requiring major airway intervention (i.e. intubation), emergent management in the operating room (i.e. rigid bronchoscopy) or admission to the paediatric intensive care unit. Our findings were compared to previous reported characteristics of children with viral croup and recurrent croup. Multiple univariate regression models were constructed to isolate predictor variables of longer hospital stay and isolate confounders such as known comorbidities and risk factors. RESULTS Sixty-seven croup patients were analyzed, aged 4–170 months (median, 15) of which 76.8% were male. Several presented with risk factors, namely previous croup history (23.2%), intubation history (13%), airway abnormalities (8.7%) and nonspecific reactive airway disease (8.7%), while others exhibited comorbid conditions such as asthma (7.3%), GERD (14.5%) and known drug allergy (5.8%). In our cohort, Parainfluenza virus type 3 (PIV3) was shown to be a predictor for increased length of stay with a univariate regression coefficient of 3.2 (95% CI 0.72–5.7). Known croup risk factors did not contribute to the effect observed with PIV3 (coefficient 3.0, 95% CI 0.4–5.7). Further analysis accounting for comorbidity confounders predicted a coefficient of 2.6 for PIV3 (95% CI 0.01–5.12). Mean length of stay for PIV3 infected children was 7.4 nights. CONCLUSION To our knowledge, this is the first study linking PIV3 with severe croup and predicting longer hospitalizations in this cohort. Further investigation is required to determine optimal management of PIV3-infected croup patients to shorten clinical course and improve patient outcomes.

Advances and Evolving Concepts in Allergic Asthma.

Allergic asthma is a heterogeneous disorder that defies a unanimously acceptable definition, but is generally recognized through its highly characteristic clinical expression of dyspnea and cough accompanied by clinical data that document reversible or exaggerated airway constriction and obstruction. The generally rising prevalence of asthma in highly industrialized societies despite significant therapeutic advances suggests that the fundamental cause(s) of asthma remain poorly understood. Detailed analyses of both the indoor (built) and outdoor environments continue to support the concept that not only inhaled particulates, especially carbon-based particulate pollution, pollens, and fungal elements, but also many noxious gases and chemicals, especially biologically derived byproducts such as proteinases, are essential to asthma pathogenesis. Phthalates, another common class of chemical pollutant found in the built environment, are emerging as potentially important mediators or attenuators of asthma. Other biological products such as endotoxin have also been confirmed to be protective in both the indoor and outdoor contexts. Proasthmatic factors are believed to activate, and in some instances initiate, pathologic inflammatory cascades through complex interactions with pattern recognition receptors (PRRs) expressed on many cell types, but especially airway epithelial cells. PRRs initiate the release of proallergic cytokines such as interleukin (IL)-33, IL-25, and others that coordinate activation of innate lymphoid cells type 2 (ILC2), T helper type 2 cells, and immunoglobulin E-secreting B cells that together promote additional inflammation and the major airway remodeling events (airway hyperresponsiveness, mucus hypersecretion) that promote airway obstruction. Proteinases, with airway fungi and viruses being potentially important sources, are emerging as critically important initiators of these inflammatory cascades in part through their effects on clotting factors such as fibrinogen. Recent clinical trials have demonstrated that targeting inflammatory pathways orchestrated through IL-4, IL-5, IL-13, and the prostaglandin receptor CRTH2 is potentially highly effective in adult asthma.

High frequency jet ventilation during endolaryngeal surgery: Risk factors for complications

Microlaryngeal surgery requires teamwork between surgeons and anesthesiologists. High-frequency jet ventilation (HFJV) is an artificial breathing technique, preferred during endolaryngeal interventions, which offers a good solution for the requirements. Most studies investigating independent risk factors for intraoperative complications during HFJV in endolaryngeal surgery (ELS) has been retrospective and not standardized and the anesthetic approach has not been standardized. This prospective cohort study aimed to identify risk factors of complications related to HFJV in ELS under a standardized anesthesia regimen. 243 patients who underwent ELS with infraglottic HFJV were investigated. Infraglottic jet ventilation catheter was placed and anesthesia was standardized. Demographic and operative data were noted. Hemodynamics, SpO2 and end-tidal CO2 were recorded at regular intervals. Complications such as hemodynamic disturbances, respiratory problems, barotrauma, equipment failure and requirement for conventional ventilation were also documented. 222 patients were included. Hypoxia, hypercapnia and the need for intubation were observed in 20(9%), 4(1.8%), 10(4.5%) patients. Bradycardia, hypotension and arrhythmia were observed in six (2.7%), 24(10.8%), and four (1.8%) patients respectively. Respiratory complications were associated with body mass index (BMI) (p < 0.001, OR: 1.57, 95%CI: 1.31–1.88) and previous major airway surgery (p < 0.001, OR: 34.0, 95%CI:3.52–328.24), whereas hemodynamic complications were associated with duration of the operation (p = 0.034, OR:1.04, 95%CI:1.0–1.09) and history of previous major airway surgery (p = 0.005, OR:9.57, 95%CI:1.97–46.49). Infraglottic HFJV can be evaluated as an alternative breathing technique to conventional ventilation during endolaryngeal interventions. However, longer operation and previous laryngeal surgeries can increase the incidence of respiratory complications.

Magnitude of Airway Problems at a University Teaching and Referral Hospital Recovery Room of Low Resource Setting-A Cross Sectional Study

Background: Airway management is a basic life-saving intervention which is used when the patient’s breathing effort is compromised due to various reasons. Postsurgical patients are at risk of developing airway problems due to co-morbidities, intraoperative complications, surgery and anaesthetic drug effects. The severity of illness, analgesic drugs like narcotics and postoperative standard of monitoring may impact on breathing process of the patients. We aimed to assess the magnitude of airway problems at the recovery room. Methods and material: Cross sectional study conducted at a referral hospital recovery room, 2014. Standardized checklist used for data collection. All patients with airway problem who admitted at the recovery room during the study period were included in the study. Descriptive statistics and Chi-square were used. Results: One hundred seventy seven patients developed airway problems over five months duration. Of these, 47.5%, 32.2%, and 20.3% patients developed mild, moderate and severe airway problems respectively. The major airway problems were desaturation (62.7%), respiratory arrest (14.7%), aspiration (18.1%), bronchospasm (3.4%) and laryngospasm (1.1%) respectively. Factors associated with severity of airway problems were ASA status (P=0.031), type of trauma (P=0.026), intraoperative analgesia (P=0.020) and type of patient (P=0.049). The interventions made were ETTI or LMA (35%) patients, nasopharyngeal airway insertion (21.5%), oral airway (14.1%), oxygen supplementation (10.2%), surgical airway (9.6%), recovery position (7.3%) and emergency airway manoeuvre (2.3%) respectively. Anaesthetists involved in airway management in 30.5% of patients. Conclusion: The magnitude of airway problem was high. We recommend the availability of well trained staff for airway management and fulfilment of basic equipments and drugs for patient monitoring and resuscitation. High airway problems are an alarm for the need for well-equipped recovery room with well trained staff, patient monitoring and resuscitation materials.

Neonatal stridor and Staphylococcus aureus: Are they related?

Staphylococcus aureus septicemia in the neonate can be complicated by the development of pneumatoceles. Affected infants usually present systemically unwell with raised inflammatory markers and worsening respiratory failure. We report the clinical progress of an extremely premature infant born at 25 weeks' gestation diagnosed with invasive S. aureus septicemia, previously stable on noninvasive respiratory support, who developed acute onset stridor on day 14 of antibiotic treatment. Further evaluation demonstrated a large pneumatocele in the right lower lobe with associated deviation of the major airways. Distortion of his trachea and right main bronchus by the pneumatocele was felt to be the most likely explanation for the acute onset of stridor. Intubation and ventilation was required for respiratory support at this stage. Of note, while there had been an acute inflammatory marker rise at the onset of the septic episode, by the development of acute stridor this had normalized, and clinically there were no acute respiratory concerns for this infant. To the best of our knowledge, this is the first reported case of a pneumatocele presenting with stridor. This case highlights the need for vigilance in extremely preterm infants with S. aureus septicemia and an awareness that pulmonary complications may arise during the recovery phase of such septic episodes.

High flow humidified nasal oxygen in pregnant women.

Failed airway management in the obstetric patient undergoing general anaesthesia is associated with major sequelae for the mother and/or fetus. Effective and adequate pre-oxygenation is an important safety strategy and a recommendation in all current major airway guidelines. Pre-oxygenation practice in the obstetric population may be suboptimal based on current literature. Recently, clinical applications for high flow nasal oxygen, also known as transnasal humidified rapid insufflation ventilatory exchange or THRIVE, are expanding in the non-obstetric population and may have theoretical benefits if used for pre-oxygenation and apnoeic oxygenation in the obstetric population. We review the current literature surrounding high flow nasal oxygen relevant to the pregnant woman. We also propose a basis for potential advantages and complications for its use in this context.

Long term radiological features of radiation-induced lung damage

PurposeTo describe the radiological findings of radiation-induced lung damage (RILD) present on CT imaging of lung cancer patients 12 months after radical chemoradiation. Material and methodsBaseline and 12-month CT scans of 33 patients were reviewed from a phase I/II clinical trial of isotoxic chemoradiation (IDEAL CRT). CT findings were scored in three categories derived from eleven sub-categories: (1) parenchymal change, defined as the presence of consolidation, ground-glass opacities (GGOs), traction bronchiectasis and/or reticulation; (2) lung volume reduction, identified through reduction in lung height and/or distortions in fissures, diaphragm, anterior junction line and major airways anatomy, and (3) pleural changes, either thickening and/or effusion. ResultsSix patients were excluded from the analysis due to anatomical changes caused by partial lung collapse and abscess. All remaining 27 patients had radiological evidence of lung damage. The three categories, parenchymal change, shrinkage and pleural change were present in 100%, 96% and 82% respectively. All patients had at least two categories of change present and 72% all three. GGOs, reticulation and traction bronchiectasis were present in 44%, 52% and 37% of patients. ConclusionsParenchymal change, lung shrinkage and pleural change are present in a high proportion of patients and are frequently identified in RILD. GGOs, reticulation and traction bronchiectasis are common at 12 months but not diagnostic.

Isolation and 3D expansion of multipotent Sox9+ mouse lung progenitors.

Multiple adult tissues are maintained by stem cells of restricted developmental potential which can only form a subset of lineages within the tissue. For instance, the two adult lung epithelial compartments (airways and alveoli) are separately maintained by distinct lineage-restricted stem cells. A challenge has been to obtain multipotent stem cells and/or progenitors that can generate all epithelial cell types of a given tissue. Here we show that mouse Sox9+ multipotent embryonic lung progenitors can be isolated and expanded long term in 3D culture. Cultured Sox9+ progenitors transcriptionally resemble their in vivo counterparts and generate both airway and alveolar cell types in vitro. Sox9+ progenitors that were transplanted into injured adult mouse lungs differentiated into all major airway and alveolar lineages in vivo in a region-appropriate fashion. We propose that a single expandable embryonic lung progenitor population with broader developmental competence may eventually be used as an alternative for region-restricted adult tissue stem cells in regenerative medicine.

Role of Smad3 and p38 Signalling in Cigarette Smoke-induced CFTR and BK dysfunction in Primary Human Bronchial Airway Epithelial Cells

Mucociliary clearance (MCC) is a major airway host defence system that is impaired in patients with smoking-associated chronic bronchitis. This dysfunction is partially related to a decrease of airway surface liquid (ASL) volume that is in part regulated by apically expressed cystic fibrosis transmembrane conductance regulator (CFTR) and large-conductance, Ca2+-activated, and voltage dependent K+ (BK) channels. Here, data from human bronchial epithelial cells (HBEC) confirm that cigarette smoke not only downregulates CFTR activity but also inhibits BK channel function, thereby causing ASL depletion. Inhibition of signalling pathways involved in cigarette smoke-induced channel dysfunction reveals that CFTR activity is downregulated via Smad3 signalling whereas BK activity is decreased via the p38 cascade. In addition, pre-treatment with pirfenidone, a drug presently used to inhibit TGF-β signalling in idiopathic pulmonary fibrosis, ameliorated BK dysfunction and ASL volume loss. Taken together, our results highlight the importance of not only CFTR but also BK channel function in maintaining ASL homeostasis and emphasize the possibility that pirfenidone could be employed as a novel therapeutic regimen to help improve MCC in smoking-related chronic bronchitis.

Catecholaminergic A1/C1 neurons contribute to the maintenance of upper airway muscle tone but may not participate in NREM sleep-related depression of these muscles

Neural mechanisms of obstructive sleep apnea, a common sleep-related breathing disorder, are incompletely understood. Hypoglossal motoneurons, which provide tonic and inspiratory activation of genioglossus (GG) muscle (a major upper airway dilator), receive catecholaminergic input from medullary A1/C1 neurons. We aimed to determine the contribution of A1/C1 neurons in control of GG muscle during sleep and wakefulness. To do so, we placed injections of a viral vector into DBH-cre mice to selectively express the hMD4i inhibitory chemoreceptors in A1/C1 neurons. Administration of the hM4Di ligand, clozapine-N-oxide (CNO), in these mice decreased GG muscle activity during NREM sleep (F1,1,3=17.1, p<0.05); a similar non-significant decrease was observed during wakefulness. CNO administration had no effect on neck muscle activity, respiratory parameters or state durations. In addition, CNO-induced inhibition of A1/C1 neurons did not alter the magnitude of the naturally occurring depression of GG activity during transitions from wakefulness to NREM sleep. These findings suggest that A1/C1 neurons have a net excitatory effect on GG activity that is most likely mediated by hypoglossal motoneurons. However, the activity of A1/C1 neurons does not appear to contribute to NREM sleep-related inhibition of GG muscle activity, suggesting that A1/C1 neurons regulate upper airway patency in a state-independent manner.