Bronchial Airway Research Articles

A Combined Computational and Experimental Study on Nanoparticle Transport and Partitioning in the Human Trachea and Upper Bronchial Airways

In the past few decades, the transport and deposition of aerosol in the human respiratory tract has been a crucial area of research, resulting in the identification of the toxicity pathways of inhaled pollutants and facilitating the design of efficient drug delivery systems for targeted treatment. Owing to the complexity of the tracheobronchial tree, experimental studies in vivo/in vitro have been extremely limited; hence, detailed data on the airflow and particle dynamics have been obtained predominantly through computational investigations. With rapid advances in medical imaging and computational capacities, sophisticated human tracheobronchial trees that include the 6th, 7th or 15th generation have been increasingly described in the literature. However, continued progress in anatomical reconstruction and mathematical idealized modeling, the two most frequently employed approaches to airway modeling, requires a detailed fundamental analysis on the morphology-induced sensitivity of particle-flow partitioning, and particle deposition in the airways. This study combined numerical and experimental investigations on the transport, deposition and partitioning of nanoparticles in the upper tracheobronchial airways. An anatomically realistic airway was reconstructed via CT scans, and a simplified numerical model was developed that incorporated physical irregularities in the trachea and assessed new boundary conditions to simulate air partitioning in the lobar bronchi, and flow and particle dynamics. An experiment measuring the penetration and deposition of sodium chloride (NaCl) nanoparticles in the anatomical and idealized airway models was conducted in parallel, and the results were compared with the computational predictions.

Outlooks of bronchial provocation pattern in obesity

Background Obesity still implies health hazards on human presented in actual increment on respiratory complaints and subsequent pulmonary derangement.Objective This study aimed to evaluate the effect of obesity on bronchial airway hyper-responsiveness and on the inflammatory markers of the airways.Participants and methods This was an observational cross-sectional study that included 98 nonasthmatic individuals who were divided into two groups according to their BMI: normal BMI and overweight or obese, with their ages ranging from 14 to 59 years. We compared the two groups on the bronchial challenge test with hypertonic saline solution 4.5%, fractional exhaled nitric oxide level, and serum level of high-sensitivity C-reactive protein.Results Positive bronchial hyper-reactivity was significantly more in overweight and obese participants compared with those with normal BMI (P=0.004). Also, bronchial hyper-reactivity was found to be significantly more common in females (P=0.025). There were statistically significant differences between the two groups in spirometry measurements, with lower lung volumes in obese participants. Moreover, statistically significant differences were observed between the two groups in fractional exhaled nitric oxide (P=0.022) and high-sensitivity C-reactive protein (P=0.043).Conclusion Obese individuals have dissimilar bronchial hyper-reactivity compared with individuals with normal BMI. Local airway and systemic inflammatory marker levels differ in obese individuals compared with those with normal BMI.

Transcriptomic profile of cystic fibrosis airway epithelial cells undergoing repair

Pathological remodeling of the airway epithelium is commonly observed in Cystic Fibrosis (CF). The different cell types that constitute the airway epithelium are regenerated upon injury to restore integrity and maintenance of the epithelium barrier function. The molecular signature of tissue repair in CF airway epithelial cells has, however, not well been investigated in primary cultures. We therefore collected RNA-seq data from well-differentiated primary cultures of bronchial human airway epithelial cells (HAECs) of CF (F508del/F508del) and non-CF (NCF) origins before and after mechanical wounding, exposed or not to flagellin. We identified the expression changes with time of repair of genes, the products of which are markers of the different cell types that constitute the airway epithelium (basal, suprabasal, intermediate, secretory, goblet and ciliated cells as well as ionocytes). Researchers in the CF field may benefit from this transcriptomic profile, which covers the initial steps of wound repair and revealed differences in this process between CF and NCF cultures.

The degree of inhomogeneity of the absorbed cell nucleus doses in the bronchial region of the human respiratory tract

Inhalation of short-lived radon progeny is an important cause of lung cancer. To characterize the absorbed doses in the bronchial region of the airways due to inhaled radon progeny, mostly regional lung deposition models, like the Human Respiratory Tract Model (HRTM) of the International Commission on Radiological Protection, are used. However, in this model the site specificity of radiation burden in the airways due to deposition and fast airway clearance of radon progeny is not described. Therefore, in the present study, the Radact version of the stochastic lung model was used to quantify the cellular radiation dose distribution at airway generation level and to simulate the kinetics of the deposited radon progeny resulting from the moving mucus layer. All simulations were performed assuming an isotope ratio typical for an average dwelling, and breathing mode characteristic of a healthy adult sitting man. The study demonstrates that the cell nuclei receiving high doses are non-uniformly distributed within the bronchial airway generations. The results revealed that the maximum of the radiation burden is at the first few bronchial airway generations of the respiratory tract, where most of the lung carcinomas of former uranium miners were found. Based on the results of the present simulations, it can be stated that regional lung models may not be fully adequate to describe the radiation burden due to radon progeny. A more realistic and precise calculation of the absorbed doses from the decay of radon progeny to the lung requires deposition and clearance to be simulated by realistic models of airway generations.

Evaluation of Bronchoscopy and Bronchoalveolar Lavage Findings in Cats With Aelurostrongylus abstrusus in Comparison to Cats With Feline Bronchial Disease.

The cat lungworm Aelurostrongylus abstrusus is a cause of lower respiratory tract disease worldwide. Bronchoscopy and bronchoalveolar lavage (BAL) are important tools for diagnosing respiratory diseases in cats. Therefore, the aim of the study was to investigate the usefulness of bronchoscopy and BAL in the diagnosis of A. abstrusus. Findings from bronchoscopic examination and BAL of 24 naturally infected cats were evaluated and compared with those of 12 cats with idiopathic Feline Bronchial Diseases (FBDs). Data were analyzed using Mann-Whitney or Fisher's exact tests. No significant bronchoscopic differences were detected between cats with aelurostrongylosis and FBDs in bronchial mucus, nodular lesions, and airway collapse. On the other hand, airway hyperemia, epithelial irregularities, and bronchial stenosis were observed more frequently in cats affected by FBDs than aelurostrongylosis, while bronchiectasis was found only in cats infected by A. abstrusus. Neutrophilic, eosinophilic, lymphocytic, and mixed inflammation were recorded in both groups. Bacteria or bacterial DNA was identified regardless of the presence or absence of A. abstrusus with no significant differences between groups. Larvae of A. abstrusus were cytologically detected in 5 of the 24 cats (20.8%) with aelurostrongylosis. These results indicate that, although some findings on bronchoscopic examination (i.e., bronchiectasis) can be described more frequently in cats infected by A. abstrusus, bronchial alterations and cytological findings in aelurostrongylosis are not specific unless larvae are observed and overlap with those of other feline airway diseases.

SAFETY AND EFFICACY OF BRONCHOSCOPY IN PREGNANCY

SESSION TITLE: Abstracts - Monday Award Semifinalists SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Bronchoscopy is a widely utilized procedure for the diagnosis and treatment of pulmonary disorders. Because of concerns for maternal and fetal safety, data on bronchoscopy in pregnancy is limited to published case reports. In this study, we performed a case series to review the safety and efficacy of bronchoscopy in the pregnant population. METHODS: A systematic literature search was performed using PubMed, EMBASE and Google scholar with key words “bronchoscopy” and “pregnancy”. Case reports involving bronchoscopy performed during pregnancy from January 1984 to December 2018 were included. Our primary objective is to evaluate the diagnostic yield of bronchoscopy in the pregnant population and the secondary objectives are to assess the occurrence of adverse events during the procedure and technical success (completion of procedure). RESULTS: Review of available literature yielded a total of 61 patients, with a mean age of 28±5 (range 18-38 years), and a mean age of gestation (AOG) of 22±8 weeks (range 6-37 weeks). Of these patients, 18% (n=11) were in the 1st trimester, 33% (n=21) in 2nd trimester, 41% (n=15) in 3rd trimester, and the remaining 8% (n=5) were not reported. The main indications for bronchoscopy were: mass (n=26, 44%), hemoptysis (n=15, 25%), unexplained dyspnea/hypoxia (n=10, 16%). Bronchoscopy was performed in 49 stable patients and 12 critically ill patients. Bronchoscopic findings were reported in 51 patients (83%), and a diagnosis was made through bronchial airway lavage and biopsy in 32 out of 41 patients (78%). Major adverse events included: hemoptysis requiring subsequent bronchoscopy or surgery (n=4, 6.5%), spontaneous abortion (n=2, 3.3%), and maternal death (n=1, 1.6%). Minor adverse events included: transient maternal hypotension (n=1, 1.6%), transient maternal hypoxia (n=1, 1.6%), and uterine contractions (n=2, 3.3%). Adverse outcomes of spontaneous abortions and maternal death occurred in patients with critical illness and in whom emergent procedure was done. Technical success was noted to be 100%. CONCLUSIONS: Diagnostic yield of bronchoscopy in pregnancy is high. Bronchoscopy is low risk for adverse events in the general population. The physiologic changes seen in pregnancy can pose an increased risk for adverse events, therefore current recommendations are to defer bronchoscopy until termination of pregnancy, or until after 2nd trimester of pregnancy. Based on our results, bronchoscopy in pregnant patients has minimal adverse outcomes, with risks occurring only in the most unstable patients. CLINICAL IMPLICATIONS: Our study demonstrates that bronchoscopy is safe in pregnancy, with high diagnostic yield and technical success, and minimal inherent adverse outcomes if performed for the right clinical indications. DISCLOSURES: No relevant relationships by Elizabeth Au, source=Web Response No relevant relationships by Jacqueline Choa, source=Web Response No relevant relationships by Chad Cross, source=Web Response No relevant relationships by Banreet Dhindsa, source=Web Response No relevant relationships by Rajany Dy, source=Web Response

Acute Respiratory Failure Secondary to Persistent Lobar Atelectasis in Ehlers-Danlos Syndrome Patient and the Role of Connective Tissue Disease in Altering the Mechanical Properties of the Lungs

Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited connective-tissue disorders characterized by joint hypermobility, cutaneous fragility, and hyperextensibility. The collagen defect has been identified in at least six of the many types of Ehlers-Danlos syndrome. Changes in the mechanical properties of the bronchial airways and lung parenchyma may trigger the observed increased tendency of the airways to collapse and lung atelectasis. This is a case of a 33 year old Caucasian female who presented with acute hypoxic respiratory failure secondary to persistent right lower lobe atelectasis despite optimal medical management, pulmonary toilet, and multiple bronchoscopies. She also had an incidental finding of lung arteriovenous malformation (AVM) which can occur in EDS patients.

Novel pendrin inhibitor attenuates airway hyperresponsiveness and mucin expression in experimental murine asthma

Novel pendrin inhibitor attenuates airway hyperresponsiveness and mucin expression in experimental murine asthma

Physiology in Perspective: The Dilemma of Muscle Weakness.

Physiology in Perspective: The Dilemma of Muscle Weakness.

Gene Expression Alterations in the Bronchial Epithelium of e-Cigarette Users

Although e-cigarette (ECIG) use has increased in the United States, their potential health effects remain uncertain. Understanding the effects of tobacco cigarette (TCIG) smoke on bronchial airway epithelial gene expression have previously provided insights into tobacco-related disease pathogenesis. Identifying the impact of ECIGs on airway gene expression could provide insights into their potential long-term health effects. We sought to compare the bronchial airway gene-expression profiles of former TCIG smokers now using ECIGs with the profiles of former and current TCIG smokers. We performed gene-expression profiling of bronchial epithelial cells collected from current TCIG smokers (n= 9), current ECIG users who are former TCIG smokers (n= 15), and former TCIG smokers (n= 21). We then compared our findings with previous studies of the effects of TCIG use on bronchial epithelium, as well an invitro model of ECIG exposure. Among 3,165 genes whose expression varied between the three study groups (q< 0.05), we identified 468 genes altered in ECIG users relative to former smokers (P< .05). Seventy-nine of these genes were up- or down-regulated concordantly among ECIG and TCIG users. We did not detect ECIG-associated gene-expression changes in known pathways associated with TCIG usage. Genes downregulated in ECIG users are enriched among the genes most downregulated by exposure of airway epithelium to ECIG vapor invitro. ECIGs induce both distinct and shared patterns of gene expression relative to TCIGs in the bronchial airway epithelium. The concordance of the genes altered in ECIG users and in the invitro study suggests that genes altered in ECIG users are likely to be changed as the direct effect of ECIG exposure.

Activation of NF-κB pathways mediating the inflammation and pulmonary diseases associated with atmospheric methylamine exposure

The effects of methylamine on human health have been debated for several years, but the exact adverse outcomes and definite signaling cascades have not been elucidated yet. Herein, a NF-κB signal pathway, a positive regulator of inflammation was identified as the main pathway of methylamine exposure induced adverse effects in bronchial airway cells (16HBE) for the first time. The results indicated that methylamine could stimulate the overproduction of reactive oxygen species (ROS) in cytoplasm and mitochondria of 16HBE cells. Moreover, ROS accelerate the translocation and phosphorylation of NF-κB in nucleic and promote the expression of inflammatory, such as IL-8 and IL-6. As a result, methylamine was found to be increased ROS-mediated NF-κB activation in cells, leading to the production of inflammatory cytokine. Furthermore, the results also showed that methylamine could affect the expression of cytokines related genes, p53, STAT3, Bcl2, c-myc, Cyclin D, Hes1, Mcl-1, TGF-β2. The breakdown of those cell proliferation and apoptosis related genes were leading to a common toxic mechanism of cell death. In summary, our work uncovers a mechanism by which methylamine can induce the formation of inflammation response and demonstrates potential inflammation and carcinogenesis in human airway cell upon the methylamine inhaled.

Numerical simulation of fibre deposition in oral and large bronchial airways in comparison with experiments

Inhaled asbestos fibres have been implicated in causal relationships with increased frequencies of non-malignant pleural disease, asbestosis, mesothelioma and lung cancer. Replacement fibres are considered to be less harmful, however, their health effects are not fully understood. The objective of the present work was to implement and apply numerical fibre tracking techniques in order to simulate the deposition of fibres in a complex oro-pharyngeal-laryngeal-bronchial system at different inhalation flow rates and compare the results with the outcomes of recent measurements performed in the same geometry. Two different approaches for the estimation of drag force were considered. Simulated deposition efficiency values agreed reasonably well with the experimentally determined values, however, the drag model which considers the anisotropic nature of the geometry of fibres performed better than the one which accounted only for the their non-spherical shape. The highest values of deposition density correlated well with the location of primary lesions observed in pathological studies.

Ultrafine particle deposition in a realistic human airway at multiple inhalation scenarios.

The scarcity of regional deposition data in distal respiratory airways represents an important challenge for current toxicology and pharmacology research. To bridge this gap, a realistic airway model extending from nasal and oral openings to distal bronchial airways with varying pathway length was built in this study. Transport and deposition characteristics of naturally inhaled ultrafine particles (UFPs) ranging from 1 to 100nm were numerically investigated, and effects of different inhalation scenarios were considered. To enable intercase particle deposition comparison, an adjusted parameter, unified deposition enhancement factor (UDEF), was proposed for quantifying the localised deposition concentration. Results show that compartment particle deposition peaked around the ultrafine end of the considered size range, and it dropped rapidly with the increase of particle size. Different inhalation modes caused notable deposition changes in the extrathoracic region, while its effects in the TB airway are much less. For UFPs larger than 10nm, predicted deposition efficiencies in all compartments are all at lowest levels among considered particle size range, implying UFPs ranging from 10 to 100nm can travel through the whole respiratory airway model and escape to the alveolar region. Furthermore, high enhancement factors were observed at the vicinity of most bifurcation apexes, and more even UDEF distribution was observed from 1-nm particle cases. While for 100-nm cases, the deposited particles tend to concentrate at few "hot spots" (areas of high deposition concentration in relation to surrounding surfaces) with greater UDEF in the tracheobronchial airway.

Role of phospholipase D in bleomycin-induced mitochondrial reactive oxygen species generation, mitochondrial DNA damage, and pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a pernicious lung disease characterized by alveolar epithelial apoptosis, dysregulated repair of epithelial injury, scar formation, and respiratory failure. In this study, we identified phospholipase D (PLD)-generated phosphatidic acid (PA) signaling in the development of pulmonary fibrosis (PF). Of the PLD isoenzymes, the protein expression of PLD2, but not PLD1, was upregulated in lung tissues from IPF patients and bleomycin challenged mice. Both PLD1 (Pld1-/-)- and PLD2 (Pld2-/-)-deficient mice were protected against bleomycin-induced lung inflammation and fibrosis, thereby establishing the role of PLD in fibrogenesis. The role of PLD1 and PLD2 in bleomycin-induced lung epithelial injury was investigated by infecting bronchial airway epithelial cells (Beas2B) with catalytically inactive mutants of PLD (hPLD1-K898R or mPld2-K758R) or downregulation of expression of PLD1 or PLD2 with siRNA. Bleomycin stimulated mitochondrial (mt) superoxide production, mtDNA damage, and apoptosis in Beas2B cells, which was attenuated by the catalytically inactive mutants of PLD or PLD2 siRNA. These results show a role for PLD1 and PLD2 in bleomycin-induced generation of mt reactive oxygen species, mt DNA damage, and apoptosis of lung epithelial cells in mice. Thus, PLD may be a novel therapeutic target in ameliorating experimental PF in mice.

Eosinophils undergo temporally regulated phenotypic and physiologic changes during influenza A virus infection

Abstract Eosinophils are traditionally known for their antiparasitic responses and as biomarkers of allergic diseases, including asthma. Using our model of asthma and influenza (AF) co-morbidity wherein disease outcomes varied by the presence of eosinophils in the airways, we determined that eosinophils played a dynamic antiviral role during influenza A virus (IAV) infections mainly by regulating CD8+ T cell immunity. We have also found that eosinophils in different niches including bone marrow, lymphoid organs, and lungs, undergo distinct immunophenotypic changes depending on the disease state in mice with asthma, influenza, or AF co-morbidity. Therefore, we hypothesized that eosinophil activation and migratory capacity are temporally regulated during IAV infection and that these changes in eosinophils are sensitive to the environment. Virus-exposure resulted in the upregulation of ICAM-1, CD69, and CD11b and downregulation of CD62L on eosinophils within 20 minutes. This expression pattern was temporally regulated suggestive of their ability sense IAV and alter functional responses such as migratory potential. Furthermore, mice infected with eosinophil pre-exposed IAV had a significantly reduced viral burden in the lungs. Eosinophils prevented IAV-induced cytopathology on lung epithelial cells when co-cultured directly or separated by transwell. In addition, eosinophil recipient IAV-infected mice showed no damage to the bronchial airway epithelium. Cumulatively, these data suggest a direct antiviral role for eosinophils through self-activation, reducing virus infectivity, and protecting the respiratory barrier from virus-induced damage further establishing an antiviral role for eosinophils in allergic airways.

Clinical features of primary tracheobronchial pulmonary amyloidosis

Objective: To analyze the clinical features of primary tracheobronchial pulmonary amyloidosis (PTBA). Methods: The records of 11 patients with PTBA diagnosed by pathology from January 2002 to June 2018 in Xiangya Hospital of Central South University were retrospectively reviewed, including clinical manifestations, laboratory and imaging examination, bronchoscopic manifestations and therapies. Meanwhile, PTBA was staged based on the severity and extent of lesion under bronchoscopy. Results: The most common clinical symptoms were cough and expectoration followed by shortness of breath and hemoptysis. Chest computed tomography (CT) revealed pulmonary infection (4/11), pulmonary nodules and masses (5/11), interstitial lesions (2/11), tracheal bronchial wall thickening (5/11) or airway stenosis (4/11). Bronchoscopy showed mucosal hypertrophy (8/11), nodular bulge (3/11), and luminal stenosis (6/11). According to the lesion involvement, 1 case only involved the lungs, 10 cases involved the trachea and/or bronchus, with (8/10) or without (2/10) lung lesions. According to the bronchoscopic staging, 2 cases (2/10) in the stage Ⅰ, lesions were limited; 2 cases (2/10) in the stage Ⅱ, lesions were diffuse; 6 cases (6/10) in the stage Ⅲ, diffuse lesions with stenosis. Conclusions: PTBA is a rare disease of the respiratory system, with unspecific clinical manifestations and diverse pulmonary imaging findings; airway mucosal hypertrophy and nodular bulging can be seen under bronchoscopy. Patients with advanced stage may present with airway stenosis.

A microphysiological model of the bronchial airways reveals the interplay of mechanical and biochemical signals in bronchospasm

In asthma, airway smooth muscle (ASM) contraction and the subsequent decrease in airflow involve a poorly understood set of mechanical and biochemical events. Organ-level and molecular-scale models of the airway are frequently based on purely mechanical or biochemical considerations and do not account for physiological mechanochemical couplings. Here, we present a microphysiological model of the airway that allows for the quantitative analysis of the interactions between mechanical and biochemical signals triggered by compressive stress on epithelial cells. We show that a mechanical stimulus mimicking a bronchospastic challenge triggers the marked contraction and delayed relaxation of ASM, and that this is mediated by the discordant expression of cyclooxygenase genes in epithelial cells and regulated by the mechanosensor and transcriptional co-activator YAP (Yes-associated protein). A mathematical model of the intercellular feedback interactions recapitulates aspects of obstructive disease of the airways, including pathognomonic features of severe, difficult-to-treat asthma. The microphysiological model could be used to investigate the mechanisms of asthma pathogenesis and to develop therapeutic strategies that disrupt the positive feedback loop that leads to persistent airway constriction.

Bioenergetic Differences in the Airway Epithelium of Lean Versus Obese Asthmatics Are Driven by Nitric Oxide and Reflected in Circulating Platelets.

Aims: Asthma, characterized by airway obstruction and hyper-responsiveness, is more severe and less responsive to treatment in obese subjects. While alterations in mitochondrial function and redox signaling have been implicated in asthma pathogenesis, it is unclear whether these mechanisms differ in lean versus obese asthmatics. In addition, we previously demonstrated that circulating platelets from asthmatic individuals have altered bioenergetics; however, it is unknown whether platelet mitochondrial changes reflect those observed in airway epithelial cells. Herein we hypothesized that lean and obese asthmatics show differential bioenergetics and redox signaling in airway cells and that these alterations could be measured in platelets from the same individual. Results: Using freshly isolated bronchial airway epithelial cells and platelets from lean and obese asthmatics and healthy individuals, we show that both cell types from obese asthmatics have significantly increased glycolysis, basal and maximal respiration, and oxidative stress compared with lean asthmatics and healthy controls. This increased respiration was associated with enhanced arginine metabolism by arginase, which has previously been shown to drive respiration. Inducible nitric oxide synthase (iNOS) was also upregulated in cells from all asthmatics. However, due to nitric oxide synthase uncoupling in obese asthmatics, overall nitric oxide (NO) bioavailability was decreased, preventing NO-dependent inhibition in obese asthmatic cells that was observed in lean asthmatics. Innovation and Conclusion: These data demonstrate bioenergetic differences between lean and obese asthmatics that are, in part, due to differences in NO signaling. They also suggest that the platelet may serve as a useful surrogate to understand redox, oxidative stress and bioenergetic changes in the asthmatic airway.

Dust mite-derived Der f 3 activates a pro-inflammatory program in airway epithelial cells via PAR-1 and PAR-2

Protease activity of allergens has been suggested to be involved in the pathogenesis of allergic diseases. The major allergen Der f 3 from Dermatophagoides farinae harbors serine protease activity, but its immunopathogenesis remains unclear. This study aims to explore the effect of Der f 3 on the airway epithelial barrier and on the molecular pathways by which Der f 3 induces inflammation. RNA-seq was performed to identify differentially expressed genes in bronchial airway epithelial cells (AEC) between native Der f 3 and heat-inactivated (H) Der f 3, coupled with real-time PCR (RT-PCR) and ELISA for validation. Unlike other protease allergens such as that induce Th2-promoting alarmins (IL-25, IL-33, TSLP) in AECs, Der f 3 induced pro-inflammatory cytokines and chemokines including IL-6, IL-8 and GM-CSF, which are known to promote Th17 response. These pro-inflammatory mediators were induced by Der f 3 via the MAPK and NF-κB pathways as well as the store-operated calcium signaling. Gene silencing with small interfering RNA in A549 and BEAS-2B cells indicated that activation of AECs by Der f 3 was mainly dependent on protease-activated receptor 2 (PAR-2), while PAR-1 was also required for the full activation of AECs. Double knock-down of PAR-1 and PAR-2 largely impaired Der f 3-inducecd IL-8 production and subsequent signaling pathways. Our data suggest that Der f 3 induces pro-inflammatory mediators in human epithelial cell lines via the PARs-MAPK-NF-κB axis. Our results provide a molecular mechanism by which Der f 3 may trigger the Th17-skewed allergic response toward house dust mites.

Numerical assessment of respiratory airway exposure risks to diesel exhaust particles

Exposure to ambient air pollution presents great adverse health risks to respiratory health, and assessing the respiratory exposure doses, especially in the human deep lung regions, remains difficult due to the sheer complexity of the process. To bridge this gap, an extended large-to-small conducting lung airway model was adopted in this study, which includes a broad scope containing bronchial airways up to the 15th generation. Accumulation mode particles in the size range of 100 nm to 3.0 μm representing major size spectrum of coarse diesel exhaust were released at the inlet of respiratory airway model, and both airflow and particle deposition characteristics were numerically investigated. The simulation results showed that the particle deposition in the respiratory airway is sensitive to the variation of inhalation flow rates. For inhalation exposure at lower breathing rate of 18 L/min, both deposited diffusive and inertia particles were very unevenly distributed in the lower respiratory airway. For inhalation exposure at higher breathing rate of 50 L/min, deposited diffusive and inertia particles were both scattered over the lower respiratory airway. In addition, high inhalation flow rate enabled inertia particles to be deposited further d ownstream of the airway with deposition hot spots observed in distal airways.