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Mouse alveolar macrophages actively patrol the alveolar airspace and mask microbial antigens to limit damaging inflammation. Restraining human neutrophil expansion during viral upper respiratory infections can avoid excessive inflammation and prevent worsened clinical outcomes. The role and landscape of type I and type III interferons during human viral respiratory infections is context, age, and anatomical region dependent. Human lungs contain long-lived tissue-resident memory T and B cells with diverse phenotypes and functions. To preserve constant air exchange and host survival, the immune system of the mammalian respiratory tract is required to balance its capacity to tolerate commensal microorganisms with protection against pathogens, while avoiding excessive and damaging inflammation. These immune functions are further influenced by the highly divergent anatomical and functional characteristics of the upper airways, trachea, and lungs. New research offers key insights into mechanisms of immune system adaptation to each unique environment, increasing our understanding of the pathogenesis of respiratory infection and (excessive) inflammation. The respiratory tract is exposed to infection from inhaled pathogens, including viruses, bacteria, and fungi. So far, a comprehensive assessment that integrates common and distinct aspects of the immune response along different areas of the respiratory tract has been lacking. Here, we discuss key recent findings regarding anatomical, functional, and microbial factors driving regional immune adaptation in the mammalian respiratory system, how they differ between mice and humans, and the similarities and differences with the gastrointestinal tract. We demonstrate that, under evolutionary pressure, mammals evolved spatially organized immune defenses that vary between the upper and lower respiratory tract. Overall, we propose that the functional specialization of the immune response along the respiratory tract has fundamental implications for the management of infectious or inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: 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. Purpose: 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. Methods: 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. Results: 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 ≥13.5 Gy. The ROC analysis further supported the superior performance of the P+A model compared to the P model in sensitivity (0.98 vs. 0.07), accuracy (0.87 vs. 0.25), and balanced predictions. Conclusions: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Single nucelotide polymorphisms (SNPs) at the FAM13A locus are among the most commonly reported risk alleles associated with chronic obstructive pulmonary disease (COPD) and other respiratory diseases; however, the physiological role of FAM13A is unclear. In humans, two major protein isoforms are expressed at the FAM13A locus: "long" and "short," but their functions remain unknown, partly because of a lack of isoform conservation in mice. We performed in-depth characterization of organotypic primary human airway epithelial cell subsets and show that multiciliated cells predominantly express the FAM13A long isoform containing a putative N-terminal Rho GTPase-activating protein (RhoGAP) domain. Using purified proteins, we directly demonstrate the RhoGAP activity of this domain. In Xenopus laevis, which conserve the long-isoform, Fam13a deficiency impaired cilia-dependent embryo motility. In human primary epithelial cells, long-isoform deficiency did not affect multiciliogenesis but reduced cilia coordination in mucociliary transport assays. This is the first demonstration that FAM13A isoforms are differentially expressed within the airway epithelium, with implications for the assessment and interpretation of SNP effects on FAM13A expression levels. We also show that the long FAM13A isoform coordinates cilia-driven movement, suggesting that FAM13A risk alleles may affect susceptibility to respiratory diseases through deficiencies in mucociliary clearance. [ABSTRACT FROM AUTHOR]

Air traffic intensity between countries and within individual countries is increasing year by year. As a rule, airways follow the same routes. As a result, so-called “roads in the sky” are formed. And where there are roads, there are bumps by the time, in the form of CAT, updraughts and downdraughts and increased turbulence. Horizontal and vertical separation plays an important role in ensuring flight safety on route. Currently, a variety of regulatory documents, defining safe separation at the flight level, has been adopted. Thus, provided there is turbulence in the vortex wake, longitudinal separation is based on the arrangement of aircraft types by three categories according to their maximum certified take-off weight. Since November 2011, the Western standard of vertical separation RVSM (Reduced Vertical Separation Minimum) has been introduced in Russia. Vertical separation is the distance between the vertical flight levels on route. Previously, this distance amounted to 600 m (2000 ft), but due to the increasing intensity of air traffic, it was decided to reduce the vertical separation to 300 m (1000 ft). Hence, at the most common flight level, the vertical separation is 300 m. The question arises if this separation ensures the safety of air transportation? The fact is that the altitude of the flight level does not necessarily coincide with the actual aircraft height. Aircraft altimeters are, inherently, calibrated barometers, that calculate the altitude by the difference in pressure on the ground and in the air. To calculate the height above ground, it would be necessary to constantly input atmospheric pressure data to altimeters at each waypoint and take into consideration the waypoint altitude above the sea level. Consequently, it is customary to use standard pressure. If the same pressure values are set on the altimeter on all aircraft, then, altitude readings on the instrument at an assigned point of airspace will be similar. Therefore, from a certain moment during the climb (transition level) to a certain moment during the descent (transition level), the aircraft height is calculated according to the standard pressure. The value of the standard pressure (QNE) is the same all over the world and amounts to 760 mmHg (1013.2 hectopascals). Thus, the flight on route is controlled by an altimeter, a barometric altimeter, which is comprised into the integrated flight and navigation system. An analysis of the instrument accuracy shows that when atmospheric pressure drops, altimeter readings may differ from true reading by ±100 m. It is known that a trailing vortex forms behind a flying plane. By the time, the trailing vortex descends and may be found at another flight level. May this cause air bump at the flight level? To answer this question, the A-380 aircraft was chosen as the object of research. This is one of the largest aircraft in the world. Therefore, the study of a trailing vortex behind the A-380 at the flight level, as the most dangerous in terms of the impact of its trailing vortex on other aircraft, will allow us to understand how safe and reasonable the accepted vertical and horizontal separation is. For the study, the special computational software system, based on the discrete vortex method, was used. This complex has passed the evaluation test and the state registration.

Eosinophilic inflammation is primarily characterized by type 2 immune responses against parasitic organisms. In the contemporary human being especially in developed countries, eosinophilic inflammation is strongly associated with allergic/sterile inflammation, and constitutes an undesired immune reaction. This situation is in stark contrast to neutrophilic inflammation, which is indispensable for the host defense against bacterial infections. Among eosinophilic inflammatory disorders, massive accumulation of eosinophils within mucus is observed in certain cases, and is often linked to the distinctive clinical finding of mucus with high viscosity. Eosinophilic mucus is found in a variety of diseases, including chronic allergic keratoconjunctivitis, chronic rhinosinusitis encompassing allergic fungal sinusitis, eosinophilic otitis media, eosinophilic sialodochitis, allergic bronchopulmonary aspergillosis/mycosis, eosinophilic plastic bronchitis, and eosinophilic asthma. In these pathological conditions, chronic inflammation and tissue remodeling coupled with irreversible organ damage due to persistent adhesion of toxic substances and luminal obstruction may impose a significant burden on the body. Eosinophils aggregate in the hyperconcentrated mucus together with cell-derived crystals, macromolecules, and polymers, thereby affecting the biophysical properties of the mucus. This review focuses on the clinically significant challenges of mucus and discusses the consequences of activated eosinophils on the mucosal surface that impact mucus and persistent inflammation.

Allergic respiratory diseases such as asthma might be considered multifactorial diseases, having a complex pathogenesis that involves environmental factors and the activation of a large set of immune response pathways and mechanisms. In addition, variations in genetic background seem to play a central role. The method developed for the analysis of the complexities, as association rule mining, nowadays may be applied to different research areas including genetic and biological complexities such as atopic airway diseases to identify complex genetic or biological markers and enlighten new diagnostic and therapeutic targets. A total of 308 allergic patients and 205 controls were typed for 13 single nucleotide polymorphisms (SNPs) of cytokine and receptors genes involved in type 1 and type 2 inflammatory response (IL-4 rs2243250 C/T, IL-4R rs1801275A/G, IL-6 rs1800795 G/C, IL-10 rs1800872 A/C and rs1800896 A/G, IL-10RB rs2834167A/G, IL-13 rs1800925 C/T, IL-18 rs187238G/C, IFNγ rs 24030561A/T and IFNγR2 rs2834213G/A), the rs2228137C/T of CD23 receptor gene and rs577912C/T and rs564481C/T of Klotho genes, using KASPar SNP genotyping method. Clinical and laboratory data of patients were analyzed by formal statistic tools and by a data-mining technique—market basket analysis—selecting a minimum threshold of 90% of rule confidence. Formal statistical analyses show that IL-6 rs1800795GG, IL-10RB rs2834167G positive genotypes, IL-13 rs1800925CC, CD23 rs2228137TT Klotho rs564481TT, might be risk factors for allergy. Applying the association rule methodology, we identify 10 genotype combination patterns associated with susceptibility to allergies. Together these data necessitate being confirmed in further studies, indicating that the heuristic approach might be a straightforward and useful tool to find predictive and diagnostic molecular patterns that might be also considered potential therapeutic targets in allergy. [ABSTRACT FROM AUTHOR]

Stereology, the gold standard of lung morphometry, critically depends on sampling of tissue for analysis. Random sampling approaches guarantee each part of the organ an equal chance of being included in the analysis; hence, they guarantee a representative sample of the whole. However, when biological or pathological structures of interest are rare and/or heterogeneously distributed over the whole lung, the random sampling approach can be inefficient or even result in meaningless data. In such cases, a targeted sampling approach can be useful, which helps to relate the analytical items to an appropriate reference space. Targeted stereology greatly benefits from the increasing availability of multiresolution imaging techniques at macroscopic and microscopic levels as well as digital tools of segmentation. As such, this article outlines two basic sampling scenarios: 1) In the first scenario, computed tomography and microscopy are subsequently used to segment the airway/arterial tree and perform stereological measurements on specific branches of the tree. 2) The second scenario deals with the heterogeneous distribution of pathological lesions. This type of analysis can be divided into two stages: assessment of lesions of interest (LOIs) within the lung and assessment of subcompartments within LOIs. Taken together, targeted stereology has a thorough foundation in stereological theory and is able to not only significantly increase the efficiency of the analysis but also yield new types of information that would be lost with the classical random sampling approach. [ABSTRACT FROM AUTHOR]

Eosinophilic inflammation is primarily characterized by type 2 immune responses against parasitic organisms. In the contemporary human being especially in developed countries, eosinophilic inflammation is strongly associated with allergic/sterile inflammation, and constitutes an undesired immune reaction. This situation is in stark contrast to neutrophilic inflammation, which is indispensable for the host defense against bacterial infections. Among eosinophilic inflammatory disorders, massive accumulation of eosinophils within mucus is observed in certain cases, and is often linked to the distinctive clinical finding of mucus with high viscosity. Eosinophilic mucus is found in a variety of diseases, including chronic allergic keratoconjunctivitis, chronic rhinosinusitis encompassing allergic fungal sinusitis, eosinophilic otitis media, eosinophilic sialodochitis, allergic bronchopulmonary aspergillosis/mycosis, eosinophilic plastic bronchitis, and eosinophilic asthma. In these pathological conditions, chronic inflammation and tissue remodeling coupled with irreversible organ damage due to persistent adhesion of toxic substances and luminal obstruction may impose a significant burden on the body. Eosinophils aggregate in the hyperconcentrated mucus together with cell-derived crystals, macromolecules, and polymers, thereby affecting the biophysical properties of the mucus. This review focuses on the clinically significant challenges of mucus and discusses the consequences of activated eosinophils on the mucosal surface that impact mucus and persistent inflammation. [ABSTRACT FROM AUTHOR]

Background: We have previously shown that asthma-like airways inflammation may be induced by topical exposure to respiratory tract pathogens such as S. pneumoniae (SP) in concert with epithelial alarmins such as IL-33. Details of the pathogenesis of this murine surrogate remain however unexplored. Methods: Airways inflammation was induced by repeated, intranasal exposure of Il-4−/−, Rag1−/− and Rag2−/−Il2rg−/− mice (in which B lymphocyte IgE switching, adaptive and innate immunity are respectively ablated) as well as wild type mice to inactivated SP, IL-33 or both. Airways pathological changes were analysed, and the subsets and functions of locally accumulated ILC2s investigated by single cell RNA sequencing and flow cytometry. Results: In the presence of IL-33, repeated exposure of the airways to inactivated SP caused marked eosinophil- and neutrophil-rich inflammation and local accumulation of ILC2s, which was retained in the Il-4−/− and Rag1−/− deficient mice but abolished in the Rag2−/−Il2rg−/− mice, an effect partly reversed by adoptive transfer of ILC2s. Single cell sequencing analysis of ILC2s recruited following SP and IL-33 exposure revealed a Klrg1+Ly6a+subset, expressing particularly elevated quantities of the pro-inflammatory cytokine IL-6, type 2 cytokines (IL-5 and IL-13) and MHC class II molecules, promoting type 2 inflammation as well as involved in neutrophil-mediated inflammatory responses. Conclusion: Local accumulation of KLRG1+Ly6a+ ILC2s in the lung tissue is a critical aspect of the pathogenesis of airways eosinophilic and neutrophil-rich inflammation induced by repeated exposure to SP in the presence of the epithelial alarmin IL-33. [ABSTRACT FROM AUTHOR]

Excessive dynamic airway collapse (EDAC) is a recognized cause of exertional dyspnea arising due to invagination of the trachea and/or main bronchi. EDAC is typically assessed by evaluating large airway movement with forced expiratory maneuvers. This differs from the respiratory response to exercise hyperpnea. We aimed to evaluate large airway movement during physical activity, with continuous bronchoscopy during exercise (CBE), in healthy subjects and compare findings with resting bronchoscopic maneuvers and imaging techniques. Twenty-eight individuals were recruited to complete two visits including treadmill-based CBE, to voluntary exhaustion, and cine magnetic resonance imaging (MRI) with forced expiratory maneuvers at rest. Twenty-five subjects [aged 29 (26–33) yr, 52% female] completed the study (n = 2 withdrew before bronchoscopy, and one was unable to tolerate insertion of bronchoscope). The majority (76%) achieved a peak heart rate of >90% predicted during CBE. The procedure was prematurely terminated in five subjects (n = 3; elevated blood pressure and n = 2; minor oxygen desaturation). The CBE assessment enabled adequate tracheal visualization in all cases. Excessive dynamic airway collapse (tracheal collapse ≥50%) was identified in 16 subjects (64%) on MRI, and in six (24%) individuals during resting bronchoscopy, but in no cases with CBE. No serious adverse events were reported, but minor adverse events were evident. The CBE procedure permits visualization of large airway movement during physical activity. In healthy subjects, there was no evidence of EDAC during strenuous exercise, despite evidence during forced maneuvers on imaging, thus challenging conventional approaches to diagnosis. NEW & NOTEWORTHY: This study demonstrates that large airway movement can be visualized with bronchoscopy undertaken during vigorous exercise. This approach does not require sedation and permits characterization of the behavior of the large airways and the tendency toward collapse during upright, ambulatory exercise. In healthy individuals, the response pattern of the large airways during exercise appears to differ markedly from the pattern of airway closure witnessed during forced expiratory maneuvers, assessed via imaging. [ABSTRACT FROM AUTHOR]

Asthma is a chronic inflammatory disease with many patients failing to respond appropriately to pharmacotherapy. Thus, virgin coconut oil (VCO) can be an alternative therapy. Guinea pigs were divided into control (Ctrl), chronic allergic lung inflammation (Asth), Asth treated with dexamethasone (Asth + dexa), and Asth supplemented with VCO (Asth + VCO4). The tested animals were sensitized and challenged with ovalbumin. Relaxation induced by arachidonic acid (AA) was impaired in Asth, and this reduction was prevented by VCO (p = 0.0004), indicating formation of relaxing prostanoids, or the decrease of cysteinyl-leukotrienes by VCO. Furthermore, a possible negative modulation of β receptors/BKCa pathway by TGF–β in Asth was prevented by VCO (p = 0.0073). Finally, in Asth, Masson’s trichrome staining revealed airway remodeling and immunohistochemistry showed increased TGF-β expression in the lungs of Asth (p

Non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) are two common respiratory tract pathogens often associated with acute exacerbations in Chronic Obstructive Pulmonary Disease (COPD) as well as with otitis media (OM) in children. Although there is evidence that these pathogens can adopt persistence mechanisms such as biofilm formation, the precise means through which they contribute to disease severity and chronicity remains incompletely understood, posing challenges for their effective eradication. The identification of potential vaccine candidates frequently entails the characterization of the host-pathogen interplay in vitro even though this approach is limited by the fact that conventional models do not permit long term bacterial infections. In the present work, by using air-liquid-interface (ALI) human airway in vitro models, we aimed to recreate COPD-related persistent bacterial infections. In particular, we explored an alternative use of the ALI system consisting in the assembly of an inverted epithelium grown on the basal part of a transwell membrane with the aim to enable the functionality of natural defense mechanisms such as mucociliary clearance and cellular extrusion that are usually hampered during conventional ALI infection experiments. The inversion of the epithelium did not affect tissue differentiation and considerably delayed NTHi or Mcat infection progression, allowing one to monitor host-pathogen interactions for up to three weeks.Notably, the use of thesemodels, coupledwith confocal and transmission electron microscopy, revealed unique features associated with NTHi and Mcat infection, highlighting persistence strategies including the formation of intracellular bacterial communities (IBCs) and surface-associated biofilm-like structures. Overall, this study demonstrates the possibility to perform long term host-pathogen investigations in vitro with the aim to define persistence mechanisms adopted by respiratory pathogens and individuate potential new vaccine targets. [ABSTRACT FROM AUTHOR]

A 13‐year‐old spayed female Persian cat presented with dyspnea and nasal discharge. Thoracic radiography revealed a dome‐shaped soft‐tissue opacity in the carina. Computed tomography confirmed a soft tissue‐attenuating mass in the carina and the left and right proximal main bronchi that appeared to arise from the tracheal wall. Tracheoscopy revealed an intraluminal broad‐based mass with multilobulated borders at the same location. Histopathological evaluation revealed a benign neoplastic process of the glandular epithelial lineage, which was considered an adenoma. Tracheal adenomas should be included in the differential diagnosis of tracheal masses. [ABSTRACT FROM AUTHOR]

Background Craniofacial skeletal discrepancies have been associated with upper airway dimensions. Objective To identify differences in upper airway volume across different sagittal and vertical skeletal patterns. Search methods Unrestricted literature searches in eight databases/registers for human studies until May 2023. Selection criteria Cross-sectional studies measuring upper airway volumes using three-dimensional imaging in healthy patients of different sagittal (Class I, Class II, and Class III) or vertical (normodivergent, hypodivergent, and hyperdivergent) craniofacial morphology. Data collection and analysis Duplicate independent study selection, data extraction, and risk of bias assessment. Random-effects frequentist network meta-analysis was performed followed by subgroup-analyses and assessment of the quality of clinical recommendations (confidence in effect estimates) with the CINeMA (Confidence in Network Meta-Analysis) approach. Results Seventy publications pertaining to 66 unique studies were included with 56 studies (5734 patients) contributing to meta-analyses. Statistically significant differences were found for total  pharyngeal airway volume, with Class II having decreased airway volume (−2256.06 mm3; 95% Confidence Interval [CI] −3201.61 to −1310.51 mm3) and Class III increased airway volume (1098.93 mm3; 95% CI 25.41 to 2172.45 mm3) compared to Class I. Significant airway volume reductions for Class II were localized mostly at the oropharynx, followed by the palatopharynx, and the glossopharynx. Significant airway volume increases for Class III were localized mostly at the oropharynx, followed by the intraoral cavity, and hypopharynx. Statistically significant differences according to vertical skeletal configuration were seen only for the oropharynx, where hyperdivergent patients had reduced volumes compared to normodivergent patients (−1716.77 mm3; 95% CI −3296.42 to −137.12 mm3). Airway differences for Class II and Class III configurations (compared to Class I) were more pronounced in adults than in children and the confidence for all estimates was very low according to CINeMA. Conclusions Considerable differences in upper airway volume were found between sagittal and vertical skeletal configurations. However, results should be interpreted with caution due to the high risk of bias, owing to the retrospective study design, inconsistencies in anatomic compartment boundaries used, samples of mixed children–adult patients, and incomplete reporting. Clinical Trial Registration PROSPERO (CRD42022366928). [ABSTRACT FROM AUTHOR]

Introduction How e-cigarette use relates to changes in smoking status and respiratory symptoms in the population remains controversial. The aim was to study the association between e-cigarette use and, changes in smoking status and changes in respiratory symptoms. Methods A prospective, population-based study of random samples of the population (age 16–69 years) was performed within The Obstructive Lung Disease in Northern Sweden (OLIN) study and West Sweden Asthma Study (WSAS). A validated postal questionnaire containing identical questions was used in OLIN and WSAS at baseline in 2006–2008 and at follow-up in 2016. In total, 17325 participated on both occasions. Questions about respiratory symptoms and tobacco smoking were included in both surveys, while e-cigarette use was added in 2016. Results In 2016, 1.6% used e-cigarettes, and it was significantly more common in persistent tobacco smokers (10.6%), than in those who quit smoking (2.1%), started smoking (7.8%), or had relapsed into tobacco smoking at follow-up (6.4%) (p

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.

INTRODUCTION How e-cigarette use relates to changes in smoking status and respiratory symptoms in the population remains controversial. The aim was to study the association between e-cigarette use and, changes in smoking status and changes in respiratory symptoms. METHODS A prospective, population-based study of random samples of the population (age 16--69 years) was performed within The Obstructive Lung Disease in Northern Sweden (OLIN) study and West Sweden Asthma Study (WSAS). A validated postal questionnaire containing identical questions was used in OLIN and WSAS at baseline in 2006--2008 and at follow-up in 2016. In total, 17325 participated on both occasions. Questions about respiratory symptoms and tobacco smoking were included in both surveys, while e-cigarette use was added in 2016. RESULTS In 2016, 1.6% used e-cigarettes, and it was significantly more common in persistent tobacco smokers (10.6%), than in those who quit smoking (2.1%), started smoking (7.8%), or had relapsed into tobacco smoking at follow-up (6.4%) (p<0.001). Among current smokers at baseline, tobacco smoking cessation was less common in e-cigarette users than e-cigarette non-users (14.2% vs 47.6%, p<0.001) and there was no association with a reduction in the number of tobacco cigarettes smoked per day. Those who were persistent smokers reported increasing respiratory symptoms. In contrast, the symptoms decreased among those who quit tobacco smoking, but there was no significant difference in respiratory symptoms between quitters with and without e-cigarette use. CONCLUSIONS E-cigarette use was associated with persistent tobacco smoking and reporting respiratory symptoms. We found no association between e-cigarette use and tobacco smoking cessation, reduction of number of tobacco cigarettes smoked per day or reduction of respiratory symptoms. [ABSTRACT FROM AUTHOR]

Asthma is an allergic airway inflammatory disease characterized by type 2 immune responses. Growing evidence suggests an association between allergic airways and intestinal diseases. However, the primary site of disease origin and initial mechanisms involved in the development of allergic airway inflammation (AAI) is not yet understood. Therefore, the initial contributing organs and mechanisms involved in the development of AAI are investigated using a mouse model of asthma. This study, without a local allergen challenge into the lungs, demonstrates a significant increase in intestinal inflammation with signature type‐2 mediators including IL‐4, IL‐13, STAT6, eosinophils, and Th2 cells. In addition, gut leakage and mRNA expressions of gut leakage markers significantly increase in the intestine. Moreover, reduced mRNA expressions of tight junction proteins are observed in gut and interestingly, in lung tissues. Furthermore, in lung tissues, an increased pulmonary barrier permeability and IL‐4 and IL‐13 levels associated with significant increase of lipopolysaccharide‐binding protein (LBP‐gut leakage marker) and eosinophils are observed. However, with local allergen challenges into the lungs, these mechanisms are further enhanced in both gut and lungs. In conclusion, the primary gut originated inflammatory responses translocates into the lungs to orchestrate AAI in a mouse model of asthma. [ABSTRACT FROM AUTHOR]

Non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) are two common respiratory tract pathogens often associated with acute exacerbations in Chronic Obstructive Pulmonary Disease (COPD) as well as with otitis media (OM) in children. Although there is evidence that these pathogens can adopt persistence mechanisms such as biofilm formation, the precise means through which they contribute to disease severity and chronicity remains incompletely understood, posing challenges for their effective eradication. The identification of potential vaccine candidates frequently entails the characterization of the host-pathogen interplay in vitro even though this approach is limited by the fact that conventional models do not permit long term bacterial infections. In the present work, by using air-liquid-interface (ALI) human airway in vitro models, we aimed to recreate COPD-related persistent bacterial infections. In particular, we explored an alternative use of the ALI system consisting in the assembly of an inverted epithelium grown on the basal part of a transwell membrane with the aim to enable the functionality of natural defense mechanisms such as mucociliary clearance and cellular extrusion that are usually hampered during conventional ALI infection experiments. The inversion of the epithelium did not affect tissue differentiation and considerably delayed NTHi or Mcat infection progression, allowing one to monitor host-pathogen interactions for up to three weeks. Notably, the use of these models, coupled with confocal and transmission electron microscopy, revealed unique features associated with NTHi and Mcat infection, highlighting persistence strategies including the formation of intracellular bacterial communities (IBCs) and surface-associated biofilm-like structures. Overall, this study demonstrates the possibility to perform long term host-pathogen investigations in vitro with the aim to define persistence mechanisms adopted by respiratory pathogens and individuate potential new vaccine targets.

Abstract Background Airway tuft cells, formerly called brush cells have long been described only morphologically in human airways. More recent RNAseq studies described a chemosensory cell population, which includes tuft cells, by a distinct gene transcription signature. Yet, until which level in the tracheobronchial tree in native human airway epithelium tuft cells occur and if they function as regulators of innate immunity, e.g., by regulating mucociliary clearance, remained largely elusive. Methods We performed immunohistochemistry, RT-PCR and immunoblotting analyses for various tuft cell markers to confirm the presence of this cell type in human tracheal samples. Immunohistochemistry was conducted to study the distribution of tuft cells along the intrapulmonary airways in humans. We assessed the influence of bitter substances and the taste transduction pathway on mucociliary clearance in mouse and human tracheal samples by measuring particle transport speed. Results Tuft cells identified by the expression of their well-established marker POU class 2 homeobox 3 (POU2F3) were present from the trachea to the bronchioles. We identified choline acetyltransferase in POU2F3 expressing cells as well as the transient receptor potential melastatin 5 (TRPM5) channel in a small population of tracheal epithelial cells with morphological appearance of tuft cells. Application of bitter substances, such as denatonium, led to an increase in mucociliary clearance in human tracheal preparations. This was dependent on activation of the TRPM5 channel and involved cholinergic and nitric oxide signalling, indicating a functional role for human tuft cells in the regulation of mucociliary clearance. Conclusions We were able to detect tuft cells in the tracheobronchial tree down to the level of the bronchioles. Moreover, taste transduction and cholinergic signalling occur in the same cells and regulate mucociliary clearance. Thus, tuft cells are potentially involved in the regulation of innate immunity in human airways.

Introduction: Coblation, a form of radiofrequency surgery, involves using radiofrequency energy to create a plasma field through a conductive medium. This technique dissociates the medium into high-energy ions that break intercellular bonds, leading to tissue dissociation. Coblation is performed at low temperatures, making it less painful and conducive to healing in airway surgeries. Aim: To evaluate the indications, advantages, and outcomes of coblation-assisted airway surgeries. Materials and Methods: A prospective cohort study was conducted from November 2019 to May 2021 at the Department of Ear, Nose and Throat (ENT), Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India. Patients with breathing difficulties, voice changes, or airway obstruction symptoms were included. A detailed history, physical examination, and diagnostic procedures were carried out. Coblation was employed under general anaesthesia for laryngeal or tracheal pathology. Data on intraoperative findings, blood loss, hospital stay, and postoperative improvements were recorded in a worksheet-based program, Numbers version 13.1 for macOS. Deductions based on the data were presented using bar charts and diagrams. Continuous variables were summarised using summary statistics, while categorical values were estimated using frequencies and percentages. Results: A total of 15 patients underwent coblation-assisted surgeries. Breathlessness was the most common symptom 11 (73.33%), followed by stridor in 10 (66.67%) and decreased oxygen levels in 8 (53.3%) were observed. Indirect laryngoscopy showed no findings compared to 70-degree scopy in detecting subglottic stenosis. Intraoperatively, 40% had Grade-II, and 27% had Grade-III subglottic stenosis. The average postoperative stay was five days. At one month, 73% showed improvement, particularly those with subglottic stenosis, while no improvement was seen in 27% of cases. Conclusion: Coblation-assisted airway surgeries offer benefits like minimal collateral damage and reduced blood loss. In this study, 73% of patients showed improvement, suggesting coblation’s potential advantages over other modalities. Although cost remains a concern, coblation’s ability to reduce postoperative morbidity and improve healing time makes it a promising tool in airway surgeries.

Beta-adrenoceptor (β-AR) agonists inhibit cholinergic contractions of airway smooth muscle (ASM), but the underlying mechanisms are unclear. ASM cells express M3 and M2 muscarinic receptors, but the bronchoconstrictor effects of acetylcholine are believed to result from activation of M3Rs, while the role of the M2Rs is confined to offsetting β-AR-dependent relaxations. However, a profound M2R-mediated hypersensitization of M3R-dependent contractions of ASM was recently reported, indicating an important role for M2Rs in cholinergic contractions of ASM. Here, we investigated if M2R-dependent contractions of murine bronchial rings were inhibited by activation of β-ARs. M2R-dependent contractions were apparent at low frequency (2Hz) electric field stimulation (EFS) and short (10s) stimulus  intervals. The β1-AR agonist, denopamine inhibited EFS-evoked contractions of ASM induced by reduction in stimulus interval from 100 to 10 s and was more effective at inhibiting contractions evoked by EFS at 2 than 20 Hz. Denopamine also abolished carbachol-evoked contractions that were resistant to the M3R antagonist 4-DAMP, similar to the effects of the M2R antagonists, methoctramine and AFDX-116. The inhibitory effects of denopamine on EFS-evoked contractions of ASM were smaller in preparations taken from M2R -/- mice, compared to wild-type (WT) controls. In contrast, inhibitory effects of the β3-AR agonist, BRL37344, on EFS-evoked contractions of detrusor strips taken from M2R -/- mice were greater than WT controls. These data suggest that M2R-dependent contractions of ASM were inhibited by activation of β1-ARs and that genetic ablation of M2Rs decreased the efficacy of β-AR agonists on cholinergic contractions.

Emerging data from clinical studies have shown pro-inflammatory effects associated with e-cigarette use. Fractional exhaled nitric oxide (FeNO) is a biomarker of pulmonary type 2 (T2) inflammation. The effect of chronic e-cigarette use on FeNO is unclear. The aim of this study was to compare FeNO levels in COPD ex-smokers who use e-cigarettes (COPDE + e-cig) to COPDE ex-smokers (COPDE) and COPD current smokers (COPDS). FeNO levels were significantly higher in COPDE + e-cig (median 16.2 ppb) and COPDE (median 18.0 ppb) compared to COPDS (median 7.6 ppb) (p = 0.0003 and p < 0.0001 respectively). There was no difference in FeNO levels between COPDE + e-cig compared to COPDE (p > 0.9). The importance of our results is that electronic cigarette use does not alter the interpretation of FeNO results, and so does not interfere with the use of FeNO as a practical biomarker of T2 inflammation, unlike current cigarette smoking in COPD. Whilst the effect of electronic cigarette use on FeNO levels is not the same as cigarette smoke, this cannot be taken as evidence that electronic cigarettes are harmless. These differential pulmonary effects can be attributed to differences in the chemical composition of the two products. • E-cigarette use does not alter the interpretation of FeNO results in COPD. • E-cigarette does not interfere with the use of FeNO as a biomarker of T2 inflammation. • This cannot be taken as evidence that e-cigarettes are harmless. [ABSTRACT FROM AUTHOR]

Foreign body airway obstruction (FBAO) is one of the most common causes of accidental death in adults and children. Probability of saving a life in severe FBAO depends on the ability of the bystander to quickly recognize the problem and correctly provide first aid (FA) to the victim. However, due to the lack of knowledge and skills of the FA, bystanders rarely attempt to give necessary help. Along with mass FA training, provision of instructions on the FA to untrained bystanders over the telephone by emergency medical services (EMS) dispatchers can facilitate active involvement of the population in the process of providing FA. In this study, a detailed analysis of the modern principles and approaches to the provision of the FA in FBAO was carried out and a draft of a universal Russian-language algorithm for remote dispatch support of the FA was developed. The developed algorithm can become a component of the domestic program for remotely instructing the population on provision of FA in life-threatening conditions and is proposed for further testing and implementation in the practice of EMS dispatchers.

Introduction: Smoking is one of the most important causes of cancer in humans. However, it has not been proven how long exposure to cigarette smoke is sufficient to induce cancerogenesis. Cigarette smoke can cause changes in ion and water transport and the maintenance of mucociliary transport. The conducted research concerned the assessment of changes in ion transport in rabbit tracheal specimens after 30 min of exposure to cigarette smoke. Materials and Methods: A modified Ussing chamber was used to measure the transepithelial electrical potential under stationary conditions (PD) and during mechanical stimulation (PDmin), and the transepithelial electrical resistance (R) in control and cigarette smoke-exposed tracheal fragments. Results: Significant changes in PD (−2.53 vs. −3.92 mV) and PDmin (−2.74 vs. −0.39 mV) were noted for the samples exposed to smoke, which can be associated with a rise in reactivity after applying a mechanical stimulus. In addition, the measured R (108 vs. 136 Ω/cm2) indicated no changes in the vitality of the samples, but an increase in their permeability to ions in the experimental conditions. Conclusions: A single 30-min exposure to cigarette smoke has been shown to be associated with increased permeability of the tracheal epithelium to ions and thus to substances emitted during smoking, which might be sufficient to create the possibility of initiating procarcinogenic processes.

Background: Due to the complexity of airways and the limitation of experiments, the production mechanism of the lung sounds in airways has not been fully understood, which often confuses diagnosis. Method: A 3D geometrical model of human airways (G5-G8) has been developed based on Weibel's model. Simulation on transient airflow and the noise production during exhalation under different breathing intensities (Q = 15, 30, 45, 60, 75, 90 L/min) has been carried out with Direct Noise Computation (DNC) and Ffowcs Williams-Hawkings (FW-H) method. Results: (1) The junctions between airways are most likely to produce lung sounds, and the peak value is located in the junction between G7 and G6 at the middle of exhalation (about 0.75 s). (2) With the increase in breathing intensity, the average sound pressure level first increases, reaches the peak value at 70–75 L/min, and then drops. (3) Higher breathing intensity is helpful to produce the feature of wheezing, namely a comparatively higher sound pressure level in the range of 200–500 Hz. Moreover, this feature is prominent with the increase in breathing intensity.

Background: Airway tuft cells, formerly called brush cells have long been described only morphologically in human airways. More recent RNAseq studies described a chemosensory cell population, which includes tuft cells, by a distinct gene transcription signature. Yet, until which level in the tracheobronchial tree in native human airway epithelium tuft cells occur and if they function as regulators of innate immunity, e.g., by regulating mucociliary clearance, remained largely elusive. Methods: We performed immunohistochemistry, RT-PCR and immunoblotting analyses for various tuft cell markers to confirm the presence of this cell type in human tracheal samples. Immunohistochemistry was conducted to study the distribution of tuft cells along the intrapulmonary airways in humans. We assessed the influence of bitter substances and the taste transduction pathway on mucociliary clearance in mouse and human tracheal samples by measuring particle transport speed. Results: Tuft cells identified by the expression of their well-established marker POU class 2 homeobox 3 (POU2F3) were present from the trachea to the bronchioles. We identified choline acetyltransferase in POU2F3 expressing cells as well as the transient receptor potential melastatin 5 (TRPM5) channel in a small population of tracheal epithelial cells with morphological appearance of tuft cells. Application of bitter substances, such as denatonium, led to an increase in mucociliary clearance in human tracheal preparations. This was dependent on activation of the TRPM5 channel and involved cholinergic and nitric oxide signalling, indicating a functional role for human tuft cells in the regulation of mucociliary clearance. Conclusions: We were able to detect tuft cells in the tracheobronchial tree down to the level of the bronchioles. Moreover, taste transduction and cholinergic signalling occur in the same cells and regulate mucociliary clearance. Thus, tuft cells are potentially involved in the regulation of innate immunity in human airways. [ABSTRACT FROM AUTHOR]

Introduction: Coblation, a form of radiofrequency surgery, involves using radiofrequency energy to create a plasma field through a conductive medium. This technique dissociates the medium into high-energy ions that break intercellular bonds, leading to tissue dissociation. Coblation is performed at low temperatures, making it less painful and conducive to healing in airway surgeries. Aim: To evaluate the indications, advantages, and outcomes of coblation-assisted airway surgeries. Materials and Methods: A prospective cohort study was conducted from November 2019 to May 2021 at the Department of Ear, Nose and Throat (ENT), Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India. Patients with breathing difficulties, voice changes, or airway obstruction symptoms were included. A detailed history, physical examination, and diagnostic procedures were carried out. Coblation was employed under general anaesthesia for laryngeal or tracheal pathology. Data on intraoperative findings, blood loss, hospital stay, and postoperative improvements were recorded in a worksheet-based program, Numbers version 13.1 for macOS. Deductions based on the data were presented using bar charts and diagrams. Continuous variables were summarised using summary statistics, while categorical values were estimated using frequencies and percentages. Results: A total of 15 patients underwent coblation-assisted surgeries. Breathlessness was the most common symptom 11 (73.33%), followed by stridor in 10 (66.67%) and decreased oxygen levels in 8 (53.3%) were observed. Indirect laryngoscopy showed no findings compared to 70-degree scopy in detecting subglottic stenosis. Intraoperatively, 40% had Grade-II, and 27% had Grade-III subglottic stenosis. The average postoperative stay was five days. At one month, 73% showed improvement, particularly those with subglottic stenosis, while no improvement was seen in 27% of cases. Conclusion: Coblation-assisted airway surgeries offer benefits like minimal collateral damage and reduced blood loss. In this study, 73% of patients showed improvement, suggesting coblation's potential advantages over other modalities. Although cost remains a concern, coblation's ability to reduce postoperative morbidity and improve healing time makes it a promising tool in airway surgeries. [ABSTRACT FROM AUTHOR]

Simple Summary: To date, the etiology of feline chronic inflammatory bronchial disease, including feline asthma, chronic bronchitis, and mixed inflammatory forms, has not extensively been investigated. By measuring allergen-specific immunoglobulin E from the serum of cats with different types of inflammatory bronchial disease and healthy cats, we aimed to obtain information on serum reactions to environmental allergens. No significant differences were found in the number of positive immunoglobulin E-reactions between affected and healthy cats. Significantly, more cats with mixed airway inflammation reacted to mites. Sensitization to environmental allergens can be detected in healthy and diseased cats. Therefore, positive reactions must always be interpreted in the context of clinical signs and environmental conditions. The etiology of feline inflammatory bronchial disease is poorly understood. This study compares the degree of allergen-specific serum IgE responses between cats with feline asthma, chronic bronchitis, mixed inflammation, and clinically healthy cats (HCs). The retrospective case–control study used serum from eighteen cats with eosinophilic inflammation (EI), ten with neutrophilic inflammation (NI), six with mixed inflammation (MI), and fourteen HCs. Affected cats were categorized into groups based on bronchoalveolar lavage cytology. The measurement of IgE for 34 different allergens including fungal organisms, weeds, grasses, trees, mites, and insects was performed using an indirect ELISA. Positive reactions to allergens were detected in the serum of 17/18 cats with EI, 8/10 with NI, 6/6 with MI, and 11/14 HCs (p = 0.364). When overall positive reactions were compared between groups, cats with MI (p = <0.01) had significantly more positive reactions against mite allergens than HCs. Blood eosinophils inversely correlated with the absolute amount of allergen-specific serum IgE expressed in ELISA absorbance units (EAs) (p = 0.014). Sensitization against dust mites seems to be more prevalent in cats with MI. However, positive IgE reactions can be observed in healthy and diseased cats, and, therefore, need to be interpreted in the light of clinical findings and environmental conditions of individual patients. [ABSTRACT FROM AUTHOR]

Background: The prevalence of asthma has been rising over the past few decades, making it one of the most prevalent chronic diseases in the world. Although the precise cause of asthma is still unknown, it most likely results from intricate interactions between a number of hereditary and environmental factors. According to the World Health Organisation (WHO), 300 million people worldwide suffer from asthma. The effects of vitamin D as a hormone have drawn more attention recently. Every component of the immune system seems to be regulated by vitamin D, with a lack of the vitamin being associated with a number of immunologically based illnesses, including asthma. Therefore, it is beneficial to check serum vitamin D levels in bronchial asthma patients. Aim and objectives: To identify any correlations between vitamin D deficiency and the severity of asthma and the objective of the study is to evaluate the serum 25(OH) D level in patients with mild, moderate, and severe asthma. Material and Methods: This is a cross-sectional observational study, which involved 100 participants between the ages of 15 and 50, of both genders with a mean age of 37.40±9.46 years. They were divided into two groups: Group A (control) consisting of 40 healthy individuals (22 males and 18 females) and Group B consisting of 60 asthmatic patients (34 males and 26 females). Group B was further subdivided into three subgroups (A, B, C), based on FEV1% and symptom severity as per the Global Initiative for Asthma (GINA) guidelines. An assay of serum vitamin D levels by ELISA was performed in both groups. Results: The results of the study demonstrated that asthmatic patients had considerably lower serum vitamin D levels than the control group. Conclusions: There is a significant inverse association between serum vitamin D levels and the severity of asthma symptoms, and vitamin D deficiency is rather common in people with asthma. As a result, when routinely evaluating individuals with asthma, serum vitamin D levels should be taken into account. It could be used to indicate the severity of asthma. [ABSTRACT FROM AUTHOR]

Background: Bronchoalveolar lavage fluid (BALF) samples are valued mirrors of different parts of the airway and can be used with other approaches to the diagnosis of the lower respiratory tract. Several previous studies on various animal species showed the effect of the season, gender, and age on the percentage of cells in the BALF samples. Aim: The main aim of this study was to determine the impact of gender, age, and season on the cytological analysis in BALF of dromedary camels. Methods: Thirteen healthy camels were involved in this study. Camels were selected based on general respiratory clinical scoring. BALF was done using a special BALF catheter. BALF samples were analyzed from dromedary camels by microscopic examination of prepared smears. Results: The results of the BALF cytology percentage revealed that there was no variation between winter and summer in most cell types. Only the mean value of neutrophil cell percentage in BALF in winter increased significantly (10.75 ± 1.31) compared to summer (4.60 ± 0.81). The range of eosinophils was in summer (0-13) wider than in winter (0-2). A significant difference was recorded in lymphocytes, eosinophils, and epithelial cells percentage among adult and young camels. There was a high mean value of epithelial cells percentage in adult camels (10.17 ± 1.64) compared to young animals (3.0 ± 0.58). The results of the BALF cytology among males and camels showed no significant difference. Conclusion: The present study revealed significant differences in the BALF cytology regarding age and season, but no impact on gender. [ABSTRACT FROM AUTHOR]

Background: Bronchoalveolar lavage fluid (BALF) samples are valued mirrors of different parts of the airway and can be used with other approaches to diagnosis of the lower respiratory tract. Several previous studies on various animal species showed the effect of the season, gender and age on the percentage of cells in the BALF samples. Aim: The main aim of this study was to determine the impact of gender, age, and season on the cytological analysis in BALF of dromedary camels. Methods: Thirteen healthy camels were involved in this study. Camels were selected based on general respiratory clinical scoring. BALF was done using a special BALF catheter. BALF samples were analyzed from dromedary camels by microscopic examination of prepared smears. Results: The results of the BALF cytology percentage revealed that there was no variation between winter and summer in most cell types. Only the mean value of neutrophil cell percentage in BALF in winter increased significantly (10.75±1.31) compared to summer (4.60±0.81). The range of eosinophils was in summer (0-13) wider than in winter (0-2). A significant difference was recorded in lymphocytes, eosinophils and epithelial cells percentage among adult and young camels. There was a high mean value of epithelial cells percentage in adult camels (10.17±1.64) comparing to young animals (3.0±0.58). The results of the BALF cytology among males and camel showed no significant difference. Conclusion: The present study revealed significant differences in the BALF cytology regarding age and season, but no impact on gender. [Open Vet J 2023; 13(5.000): 550-557]

One of the leading causes of death worldwide is represented by the respiratory diseases, which include disorders such as pneumonia, occupational lung diseases, asthma, and chronic obstructive pulmonary disease. Recent published data indicate that, in the European Union in 2017, the disorders of the respiratory system were responsible for almost 8% of all deaths [1]. Pulmonary infections could be caused by the oral colonization of possible respiratory pathogens, a process that can be promoted by the specific bacterial flora of the oral cavity or by periodontal diseases.

The acquisition of distinct branch sizes and shapes is a central aspect in tubular organ morphogenesis and function. In the Drosophila airway tree, the interplay of apical extracellular matrix (ECM) components with the underlying membrane and cytoskeleton controls tube elongation, but the link between ECM composition with apical membrane morphogenesis and tube size regulation is elusive. Here, we characterized Emp (epithelial membrane protein), a Drosophila CD36 homolog belonging to the scavenger receptor class B protein family. emp mutant embryos fail to internalize the luminal chitin deacetylases Serp and Verm at the final stages of airway maturation and die at hatching with liquid filled airways. Emp localizes in apical epithelial membranes and shows cargo selectivity for LDLr-domain containing proteins. emp mutants also display over elongated tracheal tubes with increased levels of the apical proteins Crb, DE-cad, and phosphorylated Src (p-Src). We show that Emp associates with and organizes the βH-Spectrin cytoskeleton and is itself confined by apical F-actin bundles. Overexpression or loss of its cargo protein Serp lead to abnormal apical accumulations of Emp and perturbations in p-Src levels. We propose that during morphogenesis, Emp senses and responds to luminal cargo levels by initiating apical membrane endocytosis along the longitudinal tube axis and thereby restricts airway elongation.

The global burden of respiratory diseases is very high and still on the rise, prompting the need for accurate models for basic and translational research. Several model systems are currently available ranging from simple airway cell cultures to complex tissue-engineered lungs. In recent years, human lung organoids have been established as highly transferrable three-dimensional in vitro model systems for lung research. For acute infectious and chronic inflammatory diseases as well as lung cancer, human lung organoids have opened possibilities for precise in vitro research and a deeper understanding of mechanisms underlying lung injury and regeneration. Human lung organoids from induced pluripotent stem cells or from adult stem cells of patients' samples introduce tools for understanding developmental processes and personalized medicine approaches. When further state-of-the-art technologies and protocols come into use, the full potential of human lung organoids can be harnessed. High-throughput assays in drug development, gene therapy, and organoid transplantation are current applications of organoids in translational research. In this review, we emphasize novel approaches in translational and personalized medicine in lung research focusing on the use of human lung organoids. [ABSTRACT FROM AUTHOR]

Introduction: Smoking is one of the most important causes of cancer in humans. However, it has not been proven how long exposure to cigarette smoke is sufficient to induce cancerogenesis. Cigarette smoke can cause changes in ion and water transport and the maintenance of mucociliary transport. The conducted research concerned the assessment of changes in ion transport in rabbit tracheal specimens after 30 min of exposure to cigarette smoke. Materials and Methods: A modified Ussing chamber was used to measure the transepithelial electrical potential under stationary conditions (PD) and during mechanical stimulation (PDmin), and the transepithelial electrical resistance (R) in control and cigarette smoke-exposed tracheal fragments. Results: Significant changes in PD (−2.53 vs. −3.92 mV) and PDmin (−2.74 vs. −0.39 mV) were noted for the samples exposed to smoke, which can be associated with a rise in reactivity after applying a mechanical stimulus. In addition, the measured R (108 vs. 136 Ω/cm2) indicated no changes in the vitality of the samples, but an increase in their permeability to ions in the experimental conditions. Conclusions: A single 30-min exposure to cigarette smoke has been shown to be associated with increased permeability of the tracheal epithelium to ions and thus to substances emitted during smoking, which might be sufficient to create the possibility of initiating procarcinogenic processes. [ABSTRACT FROM AUTHOR]

Helminths are not usually considered important pathogens for birds of prey. There is a single published report of mortality in raptors due to an air sac trematode infection. We report a well-documented death case from massive infection by an air sac trematode of the family Cyclocoelidae in a wild-caught, juvenile male Snail Kite (Rostrhamus sociabilis) in Ecuador. The necropsy of a Snail Kite revealed more than 200 trematodes among air sacs, lungs, heart, gizzard, proventriculus, and liver. Within air sacs and lungs, mature flukes were associated with sacculitis, bronchitis, pneumonia, and atelectasis. Using an integrative taxonomic approach with morphological and molecular data, we identified the parasites as Bothrigaster variolaris (Trematoda: Cyclocoelidae: Ophthalmophaginae). This case provides the first evidence for the pathologic presence of air sac trematodes associated with morbidity in birds of prey in South America. Our results suggest that cyclocoelids may cause debilitation and significant clinical lesions in birds of prey, with potentially fatal consequences.

Abstract Background Traffic-related air pollution (TRAP) exposure causes adverse effects on wellbeing and quality of life, which can be studied non-invasively using self-reported symptoms. However, little is known about the effects of different TRAP concentrations on symptoms following controlled exposures, where acute responses can be studied with limited confounding. We investigated the concentration–response relationship between diesel exhaust (DE) exposure, as a model TRAP, and self-reported symptoms. Methods We recruited 17 healthy non-smokers into a double-blind crossover study where they were exposed to filtered air (FA) and DE standardized to 20, 50, 150 µg/m3 PM2.5 for 4 h, with a ≥ 4-week washout between exposures. Immediately before, and at 4 h and 24 h from the beginning of the exposure, we administered visual analog scale (VAS) questionnaires and grouped responses into chest, constitutional, eye, neurological, and nasal categories. Additionally, we assessed how the symptom response was related to exposure perception and airway function. Results An increase in DE concentration raised total (β ± standard error = 0.05 ± 0.03, P = 0.04), constitutional (0.01 ± 0.01, P = 0.03) and eye (0.02 ± 0.01, P = 0.05) symptoms at 4 h, modified by perception of temperature, noise, and anxiety. These symptoms were also correlated with airway inflammation. Compared to FA, symptoms were significantly increased at 150 µg/m3 for the total (8.45 ± 3.92, P = 0.04) and eye (3.18 ± 1.55, P = 0.05) categories, with trends towards higher values in the constitutional (1.49 ± 0.86, P = 0.09) and nasal (1.71 ± 0.96, P = 0.08) categories. Conclusion DE exposure induced a concentration-dependent increase in symptoms, primarily in the eyes and body, that was modified by environmental perception. These observations emphasize the inflammatory and sensory effects of TRAP, with a potential threshold below 150 µg/m3 PM2.5. We demonstrate VAS questionnaires as a useful tool for health monitoring and provide insight into the TRAP concentration–response at exposure levels relevant to public health policy.