Airways Of Individuals Research Articles

Computational analysis on 3D airway model of obstructive sleep apnea patient for optimal maxillomandibular advancement.

Obstructive sleep apnea (OSA) can have many adverse effects on people's health, including cognitive decline and high blood pressure. Typical surgical treatment methods include the commonly performed uvulopalatopharyngoplasty and the highly successful maxillomandibular advancement (MMA). These surgical methods are more effective than non-surgical methods because they widen the airway where a collapse has occurred through direct treatment. However, few studies has shown that moving the upper and lower jaws in a specific manner is the most efficient way to treat OSA during an MMA surgery. In this study, the airway of an OSA patient was reproduced digitally, and computational fluid dynamics analysis was performed on various models with changed airway shapes, including the original model based on an actual CT image and three resizing models of the retropalatal (RP) and retroglossal (RG) regions of the airway. Consequently, it was possible to provide more quantitative predicted flow data, which could be helpful in performing sophisticated OSA surgery. Among the four airway models of the OSA patient, a reduction in the epiglottis regional pressure difference of up to 40.2% was evident in the model with an expanded RG region, and a reduction in the wall shear stress of up to 25.8% was confirmed. The proposed process could be an important aid for surgeons in determining the optimal surgical method suitable for an individual patient's uniquely-shaped airway.

Integrating the Airway Lead structure into a large healthcare system to appraise the landscape of airway management resources

Airway Leads are clinicians who guide safe airway management institutionally and act as liaisons between the evolving airway management landscape and bedside clinicians. Internationally, resources produced by Airway Leads Networks aid clinicians in establishing emergency airway management protocols and making difficult airway equipment decisions. The creation of an Airway Leads Network within the United States' multi-payer healthcare system is ongoing, spearheaded nationally by groups such as the Society for Airway Management. We aimed to build a committee of airway leaders across the Yale New Haven Health system and to leverage this committee to appraise the airway equipment and personnel resources throughout the system. We identified key stakeholders in airway management across the healthcare system and administered a quality improvement survey to members of the assembled committee querying their knowledge of the availability of airway management devices. The dataset was gathered from 14 airway management leaders identified across 4 surgical facilities, 6 emergency departments and 5 medical intensive care units at 8 hospitals and hospital campuses within the Yale New Haven Health system. Equipment available in greater than 75 % of locations included hyperangulated and standard geometry videolaryngoscopes, rigid tracheal tube stylets, tracheal tube introducers, flexible intubation scopes, scalpels and waveform capnography. Equipment available in 25 % to <75 % of locations included emergency invasive airway kits, wheeled airway towers or airway boxes, intubating oral airways, airway exchange and Aintree catheters, intubation-capable supraglottic airways, and awake intubation supplies. Glidescope (Verathon) was the most common videolaryngoscope and flexible intubation scope, and Aura (Teleflex) was the most common intubation-capable supraglottic airway available. The initiative illustrated the feasibility and utility of developing a committee of airway leaders in a large health system. While all locations had access to a requisite array of airway management devices, there was variation in the availability and brand of individual airway equipment.

Major clinical results of orthognatic surgery in obstructive sleep apnea syndrome: a systematic review

Introduction: Obstructive sleep apnea involves obstruction or narrowing of an individual's airways during sleep and is associated with several comorbidities. Management can be surgical or non-surgical, and Phase II of the Stanford Protocol for surgical management involves maxillomandibular advancement. Objective: To conduct a concise systematic review to present the main considerations and clinical results of orthognathic surgery in obstructive sleep apnea syndrome. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from April to June 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: 110 articles were found, 41 articles were evaluated and 23 were included in this systematic review. Considering the Cochrane tool for risk of bias, the global assessment resulted in 28 studies with a high risk of bias and 28 studies that did not meet GRADE. Most studies showed homogeneity in their results, with X2 =88.5% &gt;50%. Maxillomandibular advancement surgery is a successful treatment for obstructive sleep apnea, but there are still concerns about cosmetic results due to the major advances involved. Bimaxillary advancement osteotomy significantly increases oropharyngeal volume and contracted superficial areas, which remain stable between 6 months and 1 year postoperatively.

Integrating local and distant radiation-induced lung injury: Development and validation of a predictive model for ventilation loss.

Investigations on radiation-induced lung injury (RILI) have predominantly focused on local effects, primarily those associated with radiation damage to lung parenchyma. However, recent studies from our group and others have revealed that radiation-induced damage to branching serial structures such as airways and vessels may also have a substantial impact on post-radiotherapy (RT) lung function. Furthermore, recent results from multiple functional lung avoidance RT trials, although promising, have demonstrated only modest toxicity reduction, likely because they were primarily focused on dose avoidance to lung parenchyma. These observations emphasize the critical need for predictive dose-response models that effectively incorporate both local and distant RILI effects. We develop and validate a predictive model for ventilation loss after lung RT. This model, referred to as P+A, integrates local (parenchyma [P]) and distant (central and peripheral airways [A]) radiation-induced damage, modeling partial (narrowing) and complete (collapse) obstruction of airways. In an IRB-approved prospective study, pre-RT breath-hold CTs (BHCTs) and pre- and one-year post-RT 4DCTs were acquired from lung cancer patients treated with definitive RT. Up to 13 generations of airways were automatically segmented on the BHCTs using a research virtual bronchoscopy software. Ventilation maps derived from the 4DCT scans were utilized to quantify pre- and post-RT ventilation, serving, respectively, as input data and reference standard (RS) in model validation. To predict ventilation loss solely due to parenchymal damage (referred to as P model), we used a normal tissue complication probability (NTCP) model. Our model used this NTCP-based estimate and predicted additional loss due radiation-induced partial or complete occlusion of individual airways, applying fluid dynamics principles and a refined version of our previously developed airway radiosensitivity model. Predictions of post-RT ventilation were estimated in the sublobar volumes (SLVs) connected to the terminal airways. To validate the model, we conducted a k-fold cross-validation. Model parameters were optimized as the values that provided the lowest root mean square error (RMSE) between predicted post-RT ventilation and the RS for all SLVs in the training data. The performance of the P+A and the P models was evaluated by comparing their respective post-RT ventilation values with the RS predictions. Additional evaluation using various receiver operating characteristic (ROC) metrics was also performed. We extracted a dataset of 560 SLVs from four enrolled patients. Our results demonstrated that the P+A model consistently outperformed the P model, exhibiting RMSEs that were nearly half as low across all patients (13±3 percentile for the P+A model vs. 24±3 percentile for the P model on average). Notably, the P+A model aligned closely with the RS in ventilation loss distributions per lobe, particularly in regions exposed to doses ≥13.5Gy. The ROC analysis further supported the superior performance of the P+A model compared to the P model in sensitivity (0.98vs. 0.07), accuracy (0.87vs. 0.25), and balanced predictions. These early findings indicate that airway damage is a crucial factor in RILI that should be included in dose-response modeling to enhance predictions of post-RT lung function.

Growing a Cystic Fibrosis-Relevant Polymicrobial Biofilm to Probe Community Phenotypes.

Most in vitro models lack the capacity to fully probe bacterial phenotypes emerging from the complex interactions observed in real-life environments. This is particularly true in the context of hard-to-treat, chronic, and polymicrobial biofilm-based infections detected in the airways of individuals living with cystic fibrosis (CF), a multiorgan genetic disease. While multiple microbiome studies have defined the microbial compositions detected in the airway of people with CF (pwCF), no in vitro models thus far have fully integrated critical CF-relevant lung features. Therefore, a significant knowledge gap exists in the capacity to investigate the mechanisms driving the pathogenesis of mixed species CF lung infections. Here, we describe a recently developed four-species microbial community model, including Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus sanguinis, and Prevotella melaninogenica grown in CF-like conditions. Through the utilization of this system, clinically relevant phenotypes such as antimicrobialrecalcitrance of several pathogens were observed and explored at the molecular level. The usefulness of this in vitro model resides in its standardized workflow that can facilitate the study of interspecies interactions in the context of chronic CF lung infections.

Real-Time cAMP Dynamics in Live Cells Using the Fluorescent cAMP Difference Detector In Situ.

cAMP Difference Detector In Situ (cADDis) is a novel biosensor that allows for the continuous measurement of cAMP levels in living cells. The biosensor is created from a circularly permuted fluorescent protein linked to the hinge region of Epac2. This creates a single fluorophore biosensor that displays either increased or decreased fluorescence upon binding of cAMP. The biosensor exists in red and green upward versions, as well as green downward versions, and several red and green versions targeted to subcellular locations. To illustrate the effectiveness of the biosensor, the green downward version, which decreases in fluorescence upon cAMP binding, was used. Two protocols using this sensor are demonstrated: one utilizing a 96-well plate reading spectrophotometercompatible with high-throughput screening and another utilizing single-cell imaging on a fluorescent microscope. On the plate reader, HEK-293 cells cultured in 96-well plates were stimulated with 10 µM forskolin or 10 nM isoproterenol, which induced rapid and large decreases in fluorescence in the green downward version. The biosensor was used to measure cAMP levels in individual human airway smooth muscle (HASM) cells monitored under a fluorescent microscope. The green downward biosensor displayed similar responses to populations of cells when stimulated with forskolin or isoproterenol. This single-cell assay allows visualization of the biosensor location at 20x and 40x magnification. Thus, this cAMP biosensor is sensitive and flexible, allowing real-time measurement of cAMP in both immortalized and primary cells, and with single cells or populations of cells. These attributes make cADDis a valuable tool for studying cAMP signaling dynamics in living cells.

Reliable prediction of difficult airway for tracheal intubation from patient preoperative photographs by machine learning methods

BackgroundEstimating the risk of a difficult tracheal intubation should help clinicians in better anaesthesia planning, to maximize patient safety. Routine bedside screenings suffer from low sensitivity. ObjectiveTo develop and evaluate machine learning (ML) and deep learning (DL) algorithms for the reliable prediction of intubation risk, using information about airway morphology. MethodsObservational, prospective cohort study enrolling n=623 patients who underwent tracheal intubation: 53/623 difficult cases (prevalence 8.51%).First, we used our previously validated deep convolutional neural network (DCNN) to extract 2D image coordinates for 27 + 13 relevant anatomical landmarks in two preoperative photos (frontal and lateral views). Here we propose a method to determine the 3D pose of the camera with respect to the patient and to obtain the 3D world coordinates of these landmarks. Then we compute a novel set of dM=59 morphological features (distances, areas, angles and ratios), engineered with our anaesthesiologists to characterize each individual's airway anatomy towards prediction.Subsequently, here we propose four ad hoc ML pipelines for difficult intubation prognosis, each with four stages: feature scaling, imputation, resampling for imbalanced learning, and binary classification (Logistic Regression, Support Vector Machines, Random Forests and eXtreme Gradient Boosting). These compound ML pipelines were fed with the dM=59 morphological features, alongside dD=7 demographic variables. Here we trained them with automatic hyperparameter tuning (Bayesian search) and probability calibration (Platt scaling). In addition, we developed an ad hoc multi-input DCNN to estimate the intubation risk directly from each pair of photographs, i.e. without any intermediate morphological description.Performance was evaluated using optimal Bayesian decision theory. It was compared against experts' judgement and against state-of-the-art methods (three clinical formulae, four ML, four DL models). ResultsOur four ad hoc ML pipelines with engineered morphological features achieved similar discrimination capabilities: median AUCs between 0.746 and 0.766. They significantly outperformed both expert judgement and all state-of-the-art methods (highest AUC at 0.716). Conversely, our multi-input DCNN yielded low performance due to overfitting. This same behaviour occurred for the state-of-the-art DL algorithms. Overall, the best method was our XGB pipeline, with the fewest false negatives at the optimal Bayesian decision threshold. ConclusionsWe proposed and validated ML models to assist clinicians in anaesthesia planning, providing a reliable calibrated estimate of airway intubation risk, which outperformed expert assessments and state-of-the-art methods. Our novel set of engineered features succeeded in providing informative descriptions for prognosis.

The Effect of Simulated Obstructive Apneas on Mechanical Characteristics of Lower Airways in Individuals with Asthma.

Increased negative intrathoracic pressure that occurs during pharyngeal obstruction can increase thoracic fluid volume that may contribute to lower airway narrowing in individuals with obstructive sleep apnea (OSA) and asthma. Our previous study showed that fluid accumulation in the thorax induced by simulated OSA can increase total respiratory resistance. However, the effect of fluid shift on lower airway narrowing has not been investigated. To examine the effect of fluid accumulation in the thorax on the resistance of the lower airway. Non-asthma participants and individuals with (un)controlled asthma were recruited and underwent a single-day experiment. A catheter with six pressure sensors was inserted through the nose to continuously measure pressure at different sites of the airway, while a pneumotachograph was attached to a mouthpiece to record airflow. To simulate obstructive apneas, participants performed 25 Mueller maneuvers (MMs) while lying supine. Using the recordings of pressure sensor and airflow, total respiratory (RT), lower respiratory components (RL), and upper airway (RUA) resistances were calculated before and after MMs. Generalized estimation equation method was used to find the predictors of RL among variables including age, sex, body mass index, and the effect of MMs and asthma. Eighteen participants were included. Performing MMs significantly increased RT (2.23 ± 2.08 cmH2O/L/s, p = 0.003) and RL (1.52 ± 2.00 cmH2O/L/s, p = 0.023) in participants with asthma, while only RL was increased in non-asthma group (1.96 ± 1.73 cmH2O/L/s, p = 0.039). We found the model with age, and the effect of MMs and asthma severity generated the highest correlation (R2 = 0.69, p < 0.001). We provide evidence that fluid accumulation in the thorax caused by excessive intrathoracic pressure increases RL in both non-asthma and asthma groups. The changes in RL were related to age, having asthma and the effect of simulated OSA. This can explain the interrelationship between OSA and asthma.

Clinical and Ultrasonographic Assessment of Airway Indices Among Nonpregnant, Normotensive Pregnant, and Pre-eclamptic Patients: A Prospective Observational Study

(Int J Obstet Anesth. 2023:54:103637) Improper airway management is one of the leading causes of death for pregnant individuals. An ultrasound of the airway is a noninvasive tool that can be used to assess a patient’s airway and evaluate the risk of severe complications. This study aimed to compare the airways of pregnant and nonpregnant individuals using both a physical exam and an ultrasound exam.

Detailed phenotyping reveals diverse and highly skewed neutrophil subsets in both the blood and airways during active tuberculosis infection.

Neutrophils play a complex and important role in the immunopathology of TB. Data suggest they are protective during early infection but become a main driver of immunopathology if infection progresses to active disease. Neutrophils are now recognized to exist in functionally diverse states, but little work has been done on how neutrophil states or subsets are skewed in TB disease. To address this, we carried out comprehensive phenotyping by flow cytometry of neutrophils in the blood and airways of individuals with active pulmonary TB with and without HIV co-infection recruited in Durban, South Africa. Active TB was associated with a profound skewing of neutrophils in the blood toward phenotypes associated with activation and apoptosis, reduced phagocytosis, reverse transmigration, and immune regulation. This skewing was also apparently in airway neutrophils, particularly the regulatory subsets expressing PDL-1 and LOX-1. HIV co-infection did not impact neutrophil subsets in the blood but was associated with a phenotypic change in the airways and a reduction in key neutrophil functional proteins cathelicidin and arginase 1. Active TB is associated with profound skewing of blood and airway neutrophils and suggests multiple mechanisms by which neutrophils may exacerbate the immunopathology of TB. These data indicate potential avenues for reducing neutrophil-mediated lung pathology at the point of diagnosis.

An experimental study of the effect of individual upper airway anatomical features on the deposition of dry powder inhaler formulations

This study aims to investigate the effects of different pharynx anatomical features on the delivery of inhaled aerosols. Six in-vitro upper airway models reconstructed using anatomical images acquired by Magnetic Resonance Imaging (MRI) were used for the experiments. A geometrically accurate airway model was produced, and five other different airway models, each missing one or more specific anatomical features: the uvula, epiglottis, and/or soft palate, were derived from the original model. Hence, the geometrical boundaries of the six models were the same except at regions where specific anatomical structures were removed, and this was done to allow meaningful comparisons between the different geometries to be made using specific measurements. Spray-dried mannitol powder (volume median particle size and span were 3.22 μm and 1.90 μm, respectively) was loaded into a capsule-based dry powder inhaler with different resistance, an Osmohaler™ (low resistance), or Handihaler® (high resistance), attached to the inlet of the airway model, which its outlet was connected to a Next-Generation Impactor (NGI). The studies were performed using flow rates of 30 and 60 LPM. High-performance liquid chromatography (HPLC) was used to quantify the mass deposition of particles in different stages of the NGI and airway replicas. Results from this study show that widening the space between the oral cavity and oropharynx, exemplified by one of the six replicas developed, significantly decreases upper airway deposition as well as increases the fine particle fraction. The case with the highest deposition (63.5%) occurred in the pharynx replica with the soft palate present (at 60 LPM with the Hanihaler), while the lowest deposition (26.0%) occurred in the replica without the soft palate and epiglottis (at 30 LPM with the Osmohaler). This study highlights that in addition to the resistance of the inhalers, their interactions with the human airway anatomical features are likely to play important roles in the subsequent lung dose. Results from this study are novel because while the effects of different inhaler resistance in a given airway replica is known, the effects contributed by specific pharynx anatomical features on particle transport behaviour have not been studied experimentally or reported on in the literature. This study shows that space adjacent to the soft palate affects particle deposition dramatically but the effect appears to be more significant when using the Handihaler and for the high flow rate cases.

Molecular defects in primary ciliary dyskinesia are associated with agenesis of the frontal and sphenoid paranasal sinuses and chronic rhinosinusitis.

Background: Primary ciliary dyskinesia (PCD; MIM 242650) is a rare genetic disorder characterized by malfunction of the motile cilia resulting in reduced mucociliary clearance of the airways. Together with recurring infections of the lower respiratory tract, chronic rhinosinusitis (CRS) is a hallmark symptom of PCD. Data on genotype-phenotype correlations in the upper airways are scarce. Materials and methods: We investigated the prevalence, radiologic severity, and impact on health-related quality of life (HrQoL) of CRS in 58 individuals with genetically confirmed PCD. Subgroup analysis was performed according to the predicted ultrastructural phenotype based on genetic findings. Results: Among 58 individuals harboring pathogenic variants in 22 distinct genes associated with PCD, all were diagnosed with CRS, and 47% underwent sinus surgery. A total of 36 individuals answered a German-adapted version of the 20-item Sinonasal Outcome Test (SNOT-20-GAV) with a mean score of 35.8 ± 17, indicating a remarkably reduced HrQoL. Paranasal sinus imaging of 36 individuals showed moderate-to-severe opacification with an elevated Lund-Mackay Score (LMS) of 10.2 ± 4.4. Bilateral agenesis of frontal sinus (19%) and sphenoid sinus (9.5%) was a frequent finding in individuals aged 16years or older. Subgroup analysis for predicted ultrastructural phenotypes did not identify differences in HrQoL, extent of sinus opacification, or frequency of aplastic paranasal sinuses. Conclusion: PCD is strongly associated with CRS. The high burden of disease is indicated by decreased HrQoL. Therefore, the upper airways of PCD individuals should be evaluated and managed by ear-nose-throat (ENT) specialists. Genetically determined PCD groups with predicted abnormal versus (near) normal ultrastructure did not differ in disease severity. Further studies are needed to gain evidence-based knowledge of the phenotype and management of upper airway manifestations in PCD. In addition, individuals with agenesis of the frontal and sphenoid paranasal sinuses and chronic respiratory symptoms should be considered for a diagnostic evaluation of PCD.

Measuring Anatomical Distributions of Ventilation and Aerosol Deposition with PET-CT.

In disease, lung function and structure are heterogeneous, and aerosol transport and local deposition vary significantly among parts of the lung. Understanding such heterogeneity is relevant to aerosol medicine and for quantifying mucociliary clearance from different parts of the lung. In this chapter, we describe positron emission tomography (PET) imaging methods to quantitatively assess the deposition of aerosol and ventilation distribution within the lung. The anatomical information from computed tomography (CT) combined with the PET-deposition data allows estimates of airway surface concentration and peripheral tissue dosing in bronchoconstricted asthmatic subjects. A theoretical framework is formulated to quantify the effects of heterogeneous ventilation, uneven aerosol ventilation distribution in bifurcations, and varying escape from individual airways along a path of the airway tree. The framework is applied to imaging data from bronchoconstricted asthmatics to assess the contributions of these factors to the unevenness in lobar deposition. Results from this analysis show that the heterogeneity of ventilation contributes on average to more than one-third of the variability in interlobar deposition. Actual contribution of ventilation in individual lungs was variable and dependent on the breathing rate used by the subject during aerosol inhalation; the highest contribution was in patients breathing slowly. In subjects breathing faster, contribution of ventilation was reduced, with more expanded lobes showing lower deposition per unit ventilation than less expanded ones in these subjects. The lobar change in expansion measured from two static CT scans, which is commonly used as a surrogate for ventilation, did not correlate with aerosol deposition or with PET-measured ventilation. This suggests that dynamic information is needed to provide proper estimates of ventilation for asthmatic subjects. We hope that the enhanced understanding of the causes of heterogeneity in airway and tissue dosing using the tools presented here will help to optimize therapeutic effectiveness of inhalation therapy while minimizing toxicity.

Cell-Based Measurement of Mitochondrial Function in Human Airway Smooth Muscle Cells.

Cellular mitochondrial function can be assessed using high-resolution respirometry that measures the O2 consumption rate (OCR) across a number of cells. However, a direct measurement of cellular mitochondrial function provides valuable information and physiological insight. In the present study, we used a quantitative histochemical technique to measure the activity of succinate dehydrogenase (SDH), a key enzyme located in the inner mitochondrial membrane, which participates in both the tricarboxylic acid (TCA) cycle and electron transport chain (ETC) as Complex II. In this study, we determine the maximum velocity of the SDH reaction (SDHmax) in individual human airway smooth muscle (hASM) cells. To measure SDHmax, hASM cells were exposed to a solution containing 80 mM succinate and 1.5 mM nitroblue tetrazolium (NBT, reaction indicator). As the reaction proceeded, the change in optical density (OD) due to the reduction of NBT to its diformazan (peak absorbance wavelength of 570 nm) was measured using a confocal microscope with the pathlength for light absorbance tightly controlled. SDHmax was determined during the linear period of the SDH reaction and expressed as mmol fumarate/liter of cell/min. We determine that this technique is rigorous and reproducible, and reliable for the measurement of mitochondrial function in individual cells.

Abstract 218: Somatic mutations in single-cell derived alveolar organoids

Abstract The diversity in somatic variation across human tissues outshining human cancers has only recently been started to be appreciated. In particular, healthy individuals carry large numbers of cells and clonal expansions with mutations in driver genes commonly observed in cancer. We previously demonstrated that the majority of epithelial cells in the proximal airway accumulate DNA damage proportionally to an individual's smoking habits. However, the analysis of whole genomes indicated the abundance of a population of cells with a near-normal mutation burden, mirroring cellular populations found in never-smoking individuals. In contrast to the proximal airway, the genomics of cells in the distal airway of healthy individuals with diverse smoking histories, and thus the foundation of lung adenocarcinoma (LUAD), has not been investigated yet. To assess the influence of smoking on the distal airway and to compare the genomics of proximal and distal airway in the lung, we established an experimental procedure to create single-cell derived alveolar type II (AT2) organoids from primary human tissue of 9 patients. In particular, we focus on AT2 cells, given their hypothesised role as a potential cell of origin for LUAD. Whole genome sequencing (WGS) of &amp;gt;400 organoids was utilised to assess the landscape of somatic variation, including single nucleotide variants (SNVs), insertions and deletions (indels), copy number and structural variation (CNVs, SVs). Focusing on SNVs, we found that the mutation burden of never-smokers is significantly lower compared to ex- and current-smokers. Emphasising the effect of tobacco smoking on the distal airway, this difference was driven by the presence of mutations related to SBS4 and SBS92, mutational signatures associated with tobacco smoking. Interestingly, and in contrast to the proximal airway, we did not find a difference in the mutation burden of ex- and current-smokers, suggesting that smoking damage to alveolar cells is more severe and long-term. Lastly, to characterise the driver mutation landscape in depth, we used targeted single-molecule sequencing of 250 known cancer genes to profile 15 AT2 single-cell suspensions as well as 22 frozen parenchyma biopsies. To date, our preliminary results indicate positive selection on lineage defining mutations including SFTPB and SFTPC, coding for surfactant as well as TP53. As we begin to explore these data further, we expect this work to provide unprecedented insights into the contribution of somatic and driver mutations to the earliest stages of lung cancer development. Citation Format: Moritz Jakob Przybilla, Amany Ammar, Ryan Chuen Khaw, Andrew R. Lawson, Pantelis Nicola, Kate Davies, Zoe Frazer, Kate H. Gowers, Timothy M. Butler, Sarah E. Clarke, Inigo Martincorena, Sam M. Janes, Peter J. Campbell. Somatic mutations in single-cell derived alveolar organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 218.

Dose-Response Relationship between Obstructive Sleep Apnea Therapy Adherence and Healthcare Utilization.

Rationale: Clear definition of optimal positive airway pressure therapy usage in patients with obstructive sleep apnea is not possible because of scarce data on the relationship between usage hours and major clinical outcomes. Objective: To investigate the dose-response relationship between positive airway pressure usage and healthcare resource utilization and determine the minimum device usage required for benefit. Methods: A linked data set combined deidentified payer-sourced administrative medical/pharmacy claims data from more than 100 U.S. health plans and individual patient positive airway pressure usage data. Eligible adults (age ⩾18 yr) had a new obstructive sleep apnea diagnosis between June 2014 and April 2018. All received positive airway pressure therapy (AirSense 10; ResMed) with claims data for ⩾1 year before, and 2 years after, device setup. Healthcare resource utilization was determined on the basis of the number of all-cause hospitalizations and emergency room visits over 3, 12, and 24 months after positive airway pressure initiation. Results: Data from 179,188 patients showed a clear dose-response relationship between daily positive airway pressure usage and healthcare utilization. Minimum device usage required for benefit was 1-3 hours per night. There was a statistically significant decrease in hospitalizations and emergency room visits at all time points (all Ps < 0.0001) with increasing positive airway pressure usage. Each additional hour of usage per night decreased hospitalizations and emergency room visits by 5-10% and 5-7%, respectively. Conclusions: These data provide compelling evidence for a dose-response relationship between positive airway pressure usage and healthcare utilization, with benefits seen even when usage was as low as 1-2 hours per night.

Lung Inflammation in alpha-1-antitrypsin deficient individuals with normal lung function

BackgroundAlpha-1-antitrypsin deficient (AATD) individuals are prone to develop early age of onset chronic obstructive pulmonary disease (COPD) more severe than non-genetic COPD. Here, we investigated the characteristics of lower respiratory tract of AATD individuals prior to the onset of clinically significant COPD.MethodsBronchoalveolar lavage was performed on 22 AATD with normal lung function and 14 healthy individuals. Cell counts and concentrations of proteases, alpha-1-antitrypsin and proinflammatory mediators were determined in the bronchoalveolar lavage fluid from study subjects. In order to determine the airway inflammation, we also analyzed immune cell components of the large airways from bronchial biopsies using immunohistochemistry in both study subjects. Finally, we made comparisons between airway inflammation and lung function rate of decline using four repeated lung function tests over one year in AATD individuals.ResultsAATD individuals with normal lung function had 3 folds higher neutrophil counts, 2 folds increase in the proteases levels, and 2–4 folds higher levels of IL-8, IL-6, IL-1β, and leukotriene B4 in their epithelial lining fluid compared to controls. Neutrophil elastase levels showed a positive correlation with the levels of IL-8 and neutrophils in AATD epithelial lining fluid. AATD individuals also showed a negative correlation of baseline FEV1 with neutrophil count, neutrophil elastase, and cytokine levels in epithelial lining fluid (p < 0.05). In addition, we observed twofold increase in the number of lymphocytes, macrophages, neutrophils, and mast cells of AATD epithelial lining fluid as compared to controls.ConclusionMild inflammation is present in the lower respiratory tract and airways of AATD individuals despite having normal lung function. A declining trend was also noticed in the lung function of AATD individuals which was correlated with pro-inflammatory phenotype of their lower respiratory tract. This results suggest the presence of proinflammatory phenotype in AATD lungs. Therefore, early anti-inflammatory therapies may be a potential strategy to prevent progression of lung disease in AATD individuals.

Orthognathic Surgery for Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) involves obstruction or reduction of an individual's airway during sleep and is associated with several comorbidities. Patient evaluation includes detailed history, clinical and radiographic examination, endoscopy, and polysomnography. Management may be nonsurgical or surgical, and Phase II of the Stanford Protocol of surgical management involves maxillomandibular advancement (MMA). Surgical considerations (eg, degree of movement, timing of surgery) and potential complications specific to MMA are discussed in this review. With adequate planning and communication with the patient, MMA is effective in treating OSA, as measured with objective and subjective measures.

Major clinical results of orthognathic surgery and maxillomandibular advancement in obstructive sleep apnea syndrome

Introduction: Obstructive sleep apnea involves obstruction or narrowing of an individual's airway during sleep and is associated with several comorbidities. Management can be surgical or nonsurgical, and Phase II of the Stanford Protocol for surgical management involves maxillomandibular advancement. Objective: It was to carry out a concise systematic review to present the main considerations and clinical results of orthognathic surgery in obstructive sleep apnea syndrome. Methods: The systematic review rules of the PRISMA Platform were followed. The research was carried out from September to November 2022 in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 270 articles were found, 47 articles were evaluated and 23 were included in this systematic review. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 35 studies at high risk of bias and 125 studies that did not meet the GRADE. Most studies showed homogeneity in their results, with I2 =95.9% &gt;50%. Maxillomandibular advancement surgery is a successful treatment for obstructive sleep apnea, but there are still concerns about the aesthetic results due to the great advances involved. The bimaxillary advancement osteotomy significantly increases the oropharyngeal volume and constricted surface areas, which remains stable between 6 months to 1 year postoperatively.

Analysis of the primary utilization of videolaryngoscopy in prehospital emergency care in Germany.

In 2019, the German prehospital airway management guidelines were published. One of the recommendations was the primary utilization of videolaryngoscopy (VL) for every prehospital endotracheal intubation (phETI). Guideline compliance is extremely important in emergency medicine as non-compliance in the worst-case scenario leads to death. The study aims to quantify guideline compliance among emergency medical service (EMS) physicians and, subsequently to analyze subgroups influencing compliance. An online survey was developed and distributed as a hyperlink via email to all medical directors of EMS (n = 155) and the three main operators of helicopter emergency medical services (HEMS) in Germany. The survey was online from August1st 2021 until October3rd 2021. The primary outcome measure was the primary VL utilization. Data were evaluated descriptively. Amultivariate regression analysis was used to determine associations between the primary VL utilization and age, sex, educational level, specialization, phETI per year, operating field, VL device type, and guideline knowledge. The analysis included 698 EMS physicians. More than 55% of the EMS physicians do not primarily use avideolaryngoscope for phETI. Multivariate regression analysis showed asignificantly higher compliance if the devices C‑MAC® or McGrath® were on board, guidelines were known or EMS physicians were female. Age, educational level, specialization or prehospital intubation experience had no significant impact. The study shows non-compliance with prehospital airway management guidelines in Germany. The guideline recommendation is based on scientific evidence but is not yet generally accepted by all EMS physicians. Videolaryngoscope device type and sex seem to influence the primary VL utilization. Training for EMS physicians must be extended and individual prehospital airway management should be reconsidered by every EMS physician.