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Pulmonary adenocarcinoma is a malignant epithelial neoplasia that usually arises from conducting airways or alveolar parenchyma. It has rarely been described in wild felids, with no previous reports in ocelots. In domestic cats it is a very aggressive neoplasm with a high metastatic rate that usually evolves to death. This report aimed to describe a pulmonary adenocarcinoma in a captive and senile ocelot (Leopardus pardalis), with a thorough morphologic and immunophenotypically characterization, evidencing the epithelial-mesenchymal transition (EMT) phenomenon in a high metastatic carcinoma, an important feature rarely described in veterinary medicine, even in domestic cats. RESUMO O adenocarcinoma pulmonar é uma neoplasia epitelial maligna originada do epitélio respiratório das vias aéreas inferiores e do parênquima alveolar. É uma neoplasia raramente descrita em felinos selvagens, sem nenhum relato em jaguatiricas. Em gatos domésticos, é uma neoplasia muito agressiva, com alta taxa de metástase, e geralmente evolui para o óbito do paciente. O presente relato objetiva descrever um adenocarcinoma pulmonar em uma jaguatirica (Leopardus pardalis) senil de cativeiro, com detalhada caracterização morfológica e imunofenotípica, evidenciando o fenômeno de transição epitelial-mesenquial (TEM) em um carcinoma altamente metastático, uma característica importante, com escassos relatos na medicina veterinária, mesmo em gatos domésticos.

Recent evidence suggests healthy females have significantly smaller central conducting airways than males when matched for either height or lung volume during analysis. This anatomical sex-based difference could impact the integrative response to exercise. Our review critically evaluates the literature on direct and indirect techniques to measure central conducting airway size and their limitations. We present multiple sources highlighting the difference between male and female central conducting airway size in both pediatric and adult populations. Following the discussion of measurement techniques and results, we discuss the functional implications of these differences in central conducting airway size, including work of breathing, oxygen cost of breathing, and how these impacts will continue into elderly populations. We then discuss a range of topics for the future direction of airway differences and the benefits they could provide to both healthy and diseased populations. Specially, these sex-differences in central conducting airway size could result in different aerosol deposition or how lung disease manifests. Finally, we detail emerging techniques that uniquely allow for high-resolution imaging to be paired with detailed physiological measures.

The magnitude and regional heterogeneity of airway obstructions in severe asthmatics is likely linked to insufficient drug delivery, as evidenced by the inability to mitigate exacerbations with inhaled aerosol medications. To understand the correlation between morphometric features, airflow distribution, and inhaled dosimetry, we perform dynamic computational simulations in two healthy and four asthmatic subjects. Models incorporate computed tomography-based and patient-specific central airway geometries and hyperpolarized 3He MRI-measured segmental ventilation defect percentages (SVDPs), implemented as resistance boundary conditions. Particles [diameters ( dp) = 1, 3, and 5 μm] are simulated throughout inhalation, and we record their initial conditions, both spatially and temporally, with their fate in the lung. Predictions highlight that total central airway deposition is the same between the healthy subjects (26.6%, dp = 3 μm) but variable among the asthmatic subjects (ranging from 5.9% to 59.3%, dp = 3 μm). We found that by preferentially releasing the particles during times of fast or slow inhalation rates we enhance either central airway deposition percentages or peripheral particle delivery, respectively. These predictions highlight the potential to identify with simulations patients who may not receive adequate therapeutic dosages with inhaled aerosol medication and therefore identify patients who may benefit from alternative treatment strategies. Furthermore, by improving regional dose levels, we may be able to preferentially deliver drugs to the airways in need, reducing associated adverse side effects. NEW & NOTEWORTHY Although it is evident that exacerbation mitigation is unsuccessful in some asthmatics, it remains unclear whether or not these patients receive adequate dosages of inhaled therapeutics. By coupling MRI and computed tomography data with patient-specific computational models, our predictions highlight the large intersubject variability, specifically in severe asthma.

Lung cancer stem cells arise from mutations in lung epithelial stem and progenitor cells that reside in the conducting airways and alveolar bed. This chapter summarizes how the inappropriate reactivation of developmental programs, and the dynamic bidirectional communication between lung cancer stem cells and their cancerized niche, determines the course of lung cancer initiation, progression and metastasis, and the development of inter- and intra-tumor heterogeneity.

Sex-differences in the morphometry of the human respiratory system have previously been identified. Specifically, women have smaller lungs than men, even when matched for height, and women have smaller large conducting airways than men, even when matched for lung size. Moreover, the shape of the rib-cage and lungs differs based on sex. These inherent sex-differences in the structure of the respiratory system have important effects on resting pulmonary function and the integrative response to exercise. In this review, we summarize recent findings as they relate to sex-differences in the structure and function of the respiratory system. Additionally, we highlight important gaps in our understanding of the effect of sex on the anatomy and physiology of the respiratory system.

The conducting airways of the human lungs are lined by mucus, which lubricates the lung epithelium and provides a first-line protection against airborne threats. As a novel approach for visualization of the human mucus microstructure, we applied confocal Raman microscopy as a label-free and chemically selective technique. We were successfully able to chemically resolve the pulmonary surfactant from the mucus matrix and show its spatial distribution, as well as to visualize the structural changes within the freeze-dried mucus mesh upon chemical mucolysis. Subsequently, we performed rheological measurements before and after mucolysis and correlated morphology and chemical structure of the mucus with its rheological characteristics. These results do not only enrich the knowledge about the mucus microstructure, but can also, significantly contribute to rational development of future lung therapeutics.

The hypothesis that the small conducting airways were the major site of obstruction to airflow in normal lungs was introduced by Rohrer in 1915 and prevailed until Weibel introduced a quantitative method of studying lung anatomy in 1963. Green repeated Rohrer's calculations using Weibels new data in 1965 and found that the smaller conducting airways offered very little resistance to airflow. This conflict was resolved by seminal experiments conducted by Macklem and Mead in 1967, which confirmed that a small proportion of the total lower airways resistance is attributable to small airways

Introduction: A non-invasive tool to diagnose respiratory diseases and to follow treatment has long been looked-for. Exhaled nitric oxide (NO) is a promising marker of inflammation in asthma but nearly 25-years of research has shown that it works in only certain endotypes of asthma. The modelling of NO dynamics of the lung can give more information than a single FENO value.Areas covered: The estimation of the NO production in the conducting airways and in the gas exchange area has given new insight of the NO production in diseases beyond asthma. In this article, we discuss the importance of methodology for NO measurement in the exhaled breath and the indication of applying this technique to detect respiratory disorders. This narrative review is an attempt to examine and discuss the physiological basis underlying exhaled NO measurements and the clinical evidence of the usefulness of this method in asthma and various other respiratory disorders.Expert commentary: Estimation of the NO parameters woul...

Bronchopulmonary dysplasia (BPD) is a condition of neonatal chronic lung disease due to disruption or dysregulation of pulmonary development. However, the pathophysiology of BPD in the larger conducting airways is not yet fully understood. The objective of our study was to determine if the area of the central airways are altered in patients with a history of BPD. We hypothesized that compared to age- and sex-matched controls, BPD patients would have decreased area of the central conducting airways. Twenty-two BPD patients (n = 10 male, n = 12 female; median age = 10 [range:1–49] yrs) and n = 22 matched controls (n = 10 male, n = 12 female; median age = 10 [range:1–48] yrs) who had undergone a chest computed tomography (CT) scan were retrospectively identified. Measurement and analysis was performed using software that reconstructs the airways into 3D. Measurements of airway area were conducted at three points based on anatomic bifurcations for each of the following structures: trachea, left main bronchus, left upper lobe, left lower lobe, right main bronchus, intermediate bronchus, and right upper lobe. The luminal area for each airway was calculated based on the averages of the three measures. Airway luminal area was not different between BPD patients and matched controls for any of the measured airways (p > 0.05). Total lung volume detected in the CT scans was not different between BPD patients and matched controls (median [range]; 2775 [522–6215] vs 2969 [851–5612] cm3, p > 0.05). Our results suggest the luminal areas of the large conducting airways in patients with BPD are not different from matched controls.

The use of electronic cigarettes has increased exponentially since its introduction onto the global market in 2006. However, short- and long-term health effects remain largely unknown due to the novelty of this product. The present study examines the acute effects of e-cigarette aerosol inhalation, with and without nicotine, on vascular and pulmonary function in healthy volunteers. Seventeen healthy subjects inhaled electronic cigarette aerosol with and without nicotine on two separate occasions in a double-blinded crossover fashion. Blood pressure, heart rate, and arterial stiffness measured by pulse wave velocity and pulse wave analysis were assessed at baseline, and then at 0 h, 2 h, and 4 h following exposure. Dynamic spirometry and impulse oscillometry were measured following vascular assessments at these time points, as well as at 6 h following exposure. e-Cigarette aerosol with nicotine caused a significant increase in heart rate and arterial stiffness. Furthermore, e-cigarette aerosol-containing nicotine caused a sudden increase in flow resistance as measured by impulse oscillometry, indicating obstruction of the conducting airways. Both aerosols caused an increase in blood pressure. The present study indicates that inhaled e-cigarette aerosol with nicotine has an acute impact on vascular and pulmonary function. Thus, chronic usage may lead to long-term adverse health effects. Further investigation is warranted. Electronic supplementary material The online version of this article (10.1007/s12012-019-09516-x) contains supplementary material, which is available to authorized users.

Lungs are vital organs for respiration, being enabled by their complex three-dimensional organization [1]. Airway tubes bifurcate into millions of highly vascularized alveolar sacs, the alveoli, which are responsible for gas exchange. The gas exchange surface of the lungs makes up one of the largest surface areas of the human body. The alveoli receive air from the conducting airways, starting in the trachea, bifurcating into the bronchi and bronchioles, and ending in the terminal bronchioles, which divide into the alveolar ducts from which the alveoli arise.

In vivo inhalation methods for respiratory toxicity and disease in laboratory animals are time-consuming, technically demanding and of doubtful relevance for predicting effects in humans. They can also cause great suffering to the animals used. Fortunately, there has been increasing interest in developing in vitro alternatives. They can greatly simplify exposure and dosimetry, while using human cell lines and primary cells representative of all the cell types of the conducting airways. Maintained on membranes, fed basally and exposed apically at the air‒liquid interface, the cells retain their in vivo-like properties long enough for even chronic exposure and response studies to be undertaken. The predictive performance of several models is showing encouraging signs of improvement, especially when undertaken in conjunction with the latest airway particle deposition and gaseous exchange algorithms. Additional improvements in test substance delivery, automation and miniaturisation continue to be made. However, there needs to be more guidance and harmonisation applied to: (a) exposure modelling; (b) the need for exogenous metabolic activation; and (c) the use of positive and negative controls. With levels of inhalation testing and pulmonary diseases increasing, the need to expedite validation is now urgent. There are signs that the necessary dialogue and cooperation between the principal stakeholders is starting to occur, but regulatory authorities need to take the initiative to ensure that ‘actions speak louder than words’.

COVID-19 can be understood by the region of the lung that is infected. Mild disease will be confined to the conducting airways and severe disease will involve the gas exchange portion of the lung.

Recent studies have shown that small expired droplets that contain pathogens may play a significant role in the transmission of respiratory diseases. However, there is little data on the generation of droplets from the bronchioles and their deposition in the lower airways during exhalation. We apply a computational fluid dynamics method to study expiratory air flow in a truncated model of the adult lower airways. Assumptions are made to evaluate the transport and deposition of droplets along the airway as these droplets are released in various regions in the conducting airways during exhalation. We find that large droplets (i.e., >5 μm) generated from the bronchioles are very likely to be blocked by the lower airways, whereas those in the submicron range (i.e.

Background: The principle of minimal work requires that the conducting airways of human lungs should have a maximum radius for minimal resistance to gas flow. Malphigi et al said that the trachea terminated in dilated vesicle. The study of bronchial tree and their dimensions is useful in various aspects as to know the entry of foreign particles, to maintain posture for patients suffering from suppurative lung disorders. For anaesthetist to know the caliber of trachea for intubation, bronchoscopy. Bronchial anatomy is essential knowledge for thoracic surgeons in various surgical maneuvers. Methods: The study of bronchial tree is done in 20 pairs of lungs and the following are observed. Various dimensions like tracheal length, width, sub carinal angle, Length and diameter of principal bronchi from the level of bifurcation of trachea is noted with digital Vernier calipers and scale. Results: Though dimensional analysis of bronchi was studied, it shows no significance from earlier studies. In the present study all the dimensions are within normal limits. Out of 20 pairs 6 specimens showed variations in the branching patterns. Conclusions: The results suggests that there are limited variations in the dimensional study, now a days bronchoscopy procedures are widely used in diagnostic and therapeutic purposes. The sub carinal angle indirectly helps in diagnosis of cardiovascular problems and for surgical resection of segments

New Findings What is the topic of this review? This review focuses on sex-based differences in the anatomy of the respiratory system, which manifest in mechanical ventilatory contraints and potentially alter the integrative response to exercise. What advances does it highlight? Recent evidence indicates that women have smaller conducting airways than men, even when matched for lung size. Consequently, women are more likely to experience mechanical ventilatory constraints to exercise hyperpnoea. Furthermore, at a given ventilation, women have a higher work and oxygen cost of breathing, both of which may lead to differences in the whole-body integrative response to dynamic exercise. Our understanding of the human ventilatory response to exercise is largely based on a historical body of literature focused primarily on male rather than female research subjects. In recent years, important sex-based differences in the anatomy of the human respiratory system have been identified; for a given lung size, women appear to have smaller-diameter conducting airways than men. The presence of such inherent differences in the tracheobronchial tree greatly affects the mechanics of airflow generation, especially during conditions of high ventilation rates, such as exercise. Data from a growing number of studies suggest that women may be more susceptible to respiratory system limitations during exercise than their male counterparts. Specifically, women are more likely to experience expiratory flow limitation and exercise-induced arterial hypoxaemia and have a higher metabolic cost of breathing for a given ventilation. Collectively, the available evidence suggests that sex differences in the ventilatory response to exercise are present and may have important ramifications for the integrated response to exercise; however, several fundamental questions remain unanswered.

The objective of this work was to design an idealized pediatric central conducting airway model that mimics average total particle deposition in the airways of 4–8 year old children. Dimensions of the idealized model were selected based on analytical prediction of deposition in scaled versions of existing adult airway geometries. Validation experiments were then conducted using steady inhalation air flow rate to measure the deposition of monodisperse particles with mass median diameters (MMD) of 3.5, 4.5, 5 and 5.2 µm in the idealized pediatric model. The total deposition of particles was measured using gravimetry. Experimental data confirmed that aerosol deposition in the idealized pediatric central conducting airway geometry was consistent with the average deposition previously measured in 10 realistic airway replicas for children 4–8 years old.

In recent years, the ability to accurately measuring and analyzing the morphology of small pulmonary structures on chest CT images, such as airways, is becoming of great interest in the scientific community. As an example, in COPD the smaller conducting airways are the primary site of increased resistance in COPD, while small changes in airway segments can identify early stages of bronchiectasis.

The epithelium that covers the conducting airways and alveoli is a primary target for inhaled toxic substances, and therefore a focus in inhalation toxicology. The increasing concern about the use of animal models has stimulated the development of in vitro cell culture models for analysis of the biological effects of inhaled toxicants. However, the validity of the current in vitro models and their acceptance by regulatory authorities as an alternative to animal models is a reason for concern, and requires a critical review. In this review, focused on human lung epithelial cell cultures as a model for inhalation toxicology, we discuss the choice of cells for these models, the cell culture system used, the method of exposure as well as the various read-outs to assess the cellular response. We argue that rapid developments in the 3D culture of primary epithelial cells, the use of induced pluripotent stem cells for generation of lung epithelial cells and the development of organ-on-a-chip technology are among the important developments that will allow significant advances in this field. Furthermore, we discuss the various routes of application of inhaled toxicants by air-liquid interface models as well as the vast array of read-outs that may provide essential information. We conclude that close collaboration between researchers from various disciplines is essential for development of valid methods that are suitable for replacement of animal studies for inhalation toxicology.

Protracted bacterial bronchitis (PBB) is caused by a bacterial infection of the conducting airways in children who are otherwise healthy. It is the leading cause of chronic wet cough in young children and the most common reason for referrals to the Paediatric Respiratory Clinics in the UK.1 The cough has a negative effect on the quality of life of the affected child and their family.2 If PBB is left untreated, it has been postulated that ongoing endobronchial infection may be a risk factor in the development of bronchiectasis.3 The diagnosis is based on the presence of an isolated wet cough for >4 weeks, the …

Lungs are composed of a system of highly branched tubes that bring air into the alveoli, where gas exchange takes place. The proximal and distal regions of the lung contain epithelial cells specialized for different functions: basal, secretory and ciliated cells in the conducting airways and type II and type I cells lining the alveoli. Basal, secretory and type II cells can be grown in three-dimensional culture, with or without supporting stromal cells, and under these conditions they give rise to self-organizing structures known as organoids. This Review summarizes the different methods for generating organoids from cells isolated from human and mouse lungs, and compares their final structure and cellular composition with that of the airways or alveoli of the adult lung. We also discuss the potential and limitations of organoids for addressing outstanding questions in lung biology and for developing new drugs for disorders such as cystic fibrosis and asthma.

To evaluate powder formulations for pulmonary administration in pre-clinic research, the powder should be administered to the lungs of small laboratory animals. To do so properly, a device is needed that generates particles small enough to reach deep into the lungs. In this study a newly developed aerosol generator was tested for pulmonary administration of powder to the lungs of mice and its performance was compared to the only currently available device, the Penn-Century insufflator. Results showed that both devices generated powder particles of approximately the same size distribution, but the fine particle fraction needed for deep lung administration was strongly improved when the aerosol generator was used. Imaging studies in mice showed that powder particles from the aerosol generator deposited into the deep lung, where powder from the Penn-Century insufflator did not reach further than the conducting airways. Furthermore, powder administered by using the aerosol generator was more homogenously distributed over the five individual lungs lobes than powder administrated by using the Penn-Century insufflator.

The objective of this research was to obtain a correlation that quantitatively predicts micrometer-sized aerosol particle deposition in the upper conducting airways (trachea to generation 3) of children. Experiments were conducted using steady inhalation air flow rates to measure the deposition of monodisperse particles with diameters of 3.5–5.5 μm in replicas of the upper tracheobronchial airways of 11 children aged 2–8 years. The total deposition of particles was measured in each replica using gravimetry. Validation was performed by also measuring deposition in five adult replicas and the Alberta Idealized Throat and comparing with existing published data. Although there is considerable intersubject variability in our data, the empirical correlation of Chan & Lippmann (1980) was found to predict total deposition reasonably well in all of our adult and child replicas.

This unit focuses on protocols for assessing microenvironment-specific responses in the thoracic lung tissues. Aspects of the entire respiratory system serve as potential targets for candidate toxicants, but each candidate toxicant may impact distinct sites due to differential distribution of either the toxicant or the target cells. Within the conducting airways, the composition of resident cell populations and the metabolic capabilities of the cell populations vary greatly. Thus, studies of this region of the lung require unique, site-selective methods to clearly define the toxic response. Without site-specific sampling, as described in this chapter, the experimental limit of detection for toxicant effects in conducting airways is weakened because differences unrelated to treatment, but related to location, may dominate the response. The protocols included here allow assessment of toxicological responses in the tracheobronchial airways and the gas exchange area of the lung, with specific application to laboratory mammals. © 2017 by John Wiley & Sons, Inc.

The structure of the lung subserves its function, which is primarily gas exchange, and selection for expanded capacities for gas exchange is self-evident in the great diversity of pulmonary morphologies observed in different vertebrate lineages. However, expansion of aerobic capacities does not explain all of this diversity, leaving the functional underpinnings of some of the most fascinating transformations of the vertebrate lung unknown. One of these transformations is the evolution of highly branched conducting airways, particularly those of birds and mammals. Birds have an extraordinarily complex circuit of airways through which air flows in the same direction during both inspiration and expiration, unidirectional flow. Mammals also have an elaborate system of conducting airways; however, the tubes arborize rather than form a circuit, and airflow is tidal along the branches of the bronchial tree. The discovery of unidirectional airflow in crocodilians and lizards indicates that several inveterate hypotheses for the selective drivers of this trait cannot be correct. Neither endothermy nor athleticism drove the evolution of unidirectional flow. These discoveries open an uncharted area for research into selective underpinning of unidirectional airflow.

To fulfill the task of gas exchange, the lung possesses a huge inner surface and a tree-like system of conducting airways ventilating the gas exchange area. During lung development, the conducting airways are formed first, followed by the formation and enlargement of the gas exchange area. The latter (alveolarization) continues until young adulthood. During organogenesis, the left and right lungs have their own anlage, an outpouching of the foregut. Each lung bud starts a repetitive process of outgrowth and branching (branching morphogenesis) that forms all of the future airways mainly during the pseudoglandular stage. During the canalicular stage, the differentiation of the epithelia becomes visible and the bronchioalveolar duct junction is formed. The location of this junction stays constant throughout life. Towards the end of the canalicular stage, the first gas exchange may take place and survival of prematurely born babies becomes possible. Ninety percent of the gas exchange surface area will be formed by alveolarization, a process where existing airspaces are subdivided by the formation of new walls (septa). This process requires a double-layered capillary network at the basis of the newly forming septum. However, in parallel to alveolarization, the double-layered capillary network of the immature septa fuses to a single-layered network resulting in an optimized setup for gas exchange. Alveolarization still continues, because, at sites where new septa are lifting off preexisting mature septa, the required second capillary layer will be formed instantly by angiogenesis. The latter confirms a lifelong ability of alveolarization, which is important for any kind of lung regeneration.

Deposition characteristics of MDI and DPI aerosols were compared throughout the conducting airways for the first time using a combination of in vitro experiments and a newly developed stochastic individual path (SIP) model for different inhalation profiles. In vitro experiments were used to determine initial particle distribution profiles and to validate computational fluid dynamics (CFD) model results for a MDI and DPI delivering the same dose of drug in a geometry of the mouth-throat and tracheobronchial airways. The validated CFD model was then used to predict the transport and deposition of the drug using correct and incorrect inhalation profiles for each inhaler. The MDI delivered approximately two times more drug to the tracheobronchial region compared with the DPI for both correct and incorrect inhalation profiles. Errors in inhalation reduced the deposited tracheobronchial dose by approximately 30% for both inhalers. The DPI delivered the largest dose to the mouth-throat (~70%) and the MDI delivered the largest dose to the alveolar airways (~50%). The developed in silico model provides new insights into the lung delivery of pharmaceutical aerosols and can be applied in future studies in combination with pharmacokinetic analysis to establish bioequivalence between devices.

Tobacco smoking during pregnancy remains common, especially in indigenous communities, and likely contributes to respiratory illness in exposed offspring. It is now well established that components of tobacco smoke, notably nicotine, can affect multiple organs in the fetus and newborn, potentially with life-long consequences. Recent studies have shown that nicotine can permanently affect the developing lung such that its final structure and function are adversely affected; these changes can increase the risk of respiratory illness and accelerate the decline in lung function with age. In this review we discuss the impact of maternal smoking on the lungs and consider the evidence that smoking can have life-long, programming consequences for exposed offspring. Exposure to maternal tobacco smoking and nicotine intake during pregnancy and lactation changes the genetic program that controls the development and aging of the lungs of the offspring. Changes in the conducting airways and alveoli reduce lung function in exposed offspring, rendering the lungs more susceptible to obstructive lung disease and accelerating lung aging. Although it is generally accepted that prevention of maternal smoking during pregnancy and lactation is essential, current knowledge of the effects of nicotine on lung development does not support the use of nicotine replacement therapy in this group.

In the airway network of a human lung, the airway diameter gradually decreases through multiple branching. The diameter reduction ratio of the conducting airways that transport gases without gas exchange is 0.79, but this reduction ratio changes to 0.94 in acinar airways beyond transitional bronchioles. While the reduction in the conducting airways was previously rationalized on the basis of Murray’s law, our understanding of the design principle behind the acinar airways has been far from clear. Here we elucidate that the change in gas transfer mode is responsible for the transition in the diameter reduction ratio. The oxygen transfer rate per unit surface area is maximized at the observed geometry of acinar airways, which suggests the minimum cost for the construction and maintenance of the acinar airways. The results revitalize and extend the framework of Murray’s law over an entire human lung.

Different thermometers have been constructed over the decades to measure the temperature of the body to help detect and monitor morbid states. They yield slightly different estimates of the core body temperature depending on the proximity of the measurement site to the internal milieu of the organism, the principle of temperature assessment, and the specific characteristics of the gauging devices. Evaluation of the exhaled breath temperature (EBT) has been recently suggested as a new method to detect inflammatory processes in the conducting airways due to changes in the blood flow perfusion of their walls and adjacent structures. While the first reported EBT experiments required sealed laboratory environment and sophisticated equipment, we designed a simple handheld instrument for EBT measurement and proven its precision, reproducibility and validity in subjects with asthma. We now describe the construction principles of our instrument, the procedure to test the fitness for purpose of the separate units and the novel features of the newest prototypes outfitted with microprocessor and memory. We also outline the potential clinical applications of an individual device for EBT measurement.

Status asthmaticus (SA) is a severe, refractory form of asthma that can result in rapid respiratory deterioration and death. Treatment of SA with inhaled anesthetics is a potentially life-saving therapy, but remarkably few data are available about its mechanism of action or optimal administration. In this paper, we will review the clinical use of inhaled anesthetics for treatment of SA, the potential mechanisms by which they dilate constricted airways, and the side effects associated with their administration. We will also introduce the concept of 'targeted' delivery of these agents to the conducting airways, a process which may maximize their therapeutic effects while minimizing associated systemic side effects. Such a delivery regimen has the potential to define a rapidly translatable treatment paradigm for this life-threatening disorder.

Background: Lung transplantation (LT) is a recognized treatment for end-stage pulmonary disease. Bacteria from the recipient nasopharynx seed the new lungs leading to infections and allograft damage. Understanding the characteristics and topological variations of the microbiota may be important to apprehend the pathophysiology of allograft dysfunction. Objectives: To examine the characteristics and relationship of bacterial compositions between conducting and respiratory zones of the allograft. Methods: We performed 16S rRNA gene sequencing on bronchial aspirates (BAs) and bronchoalveolar lavages (BALs) collected in pairs in 19 patients at several time-points post-LT. Results: The respiratory zone was characterized independently of the time post-LT by a higher bacterial richness than the conducting zone (p = 0.041). The phyla Firmicutes and Proteobacteria dominated both sampling zones, with an inverse correlation between these two phyla (Spearman r = -0.830). Samples of the same pair, as well as pairs from the same individual clustered together (Pseudo-F = 3.8652, p < 0.01). Microbiota of BA and BAL were more closely related in samples from the same patient than each sample type across different patients, with variation in community structure being mainly inter-individual (p < 0.01). Both number of antibiotics administered (p < 0.01) and time interval post-LT (p < 0.01) contributed to the variation in global microbiota structure. Longitudinal analysis of BA-BAL pairs of two patients showed dynamic wave like fluctuations of the microbiota. Conclusions: Our results show that post-transplant respiratory zones harbor higher bacterial richness, but overall similar bacterial profiles as compared to conductive zones. They further support an individual microbial signature following LT.

A multi-compartment model for the clearance of insoluble particles from the tracheobronchial tree of the human lung was created. As a significant innovation, the model considers specific mass transfer paths that may play an important role for slow bronchial clearance. These include the accumulation of particulate mass in the periciliary sol layer, an uptake of stored particles by airway macrophages, and the endocytosis of deposited mass by epithelial cells. Besides the gel layer representing fast mucociliary clearance, all cellular and extracellular units involved into the slow clearance process are described by respective compartments which are connected by specific transfer paths. The gastrointestinal tract (GIT), lymph nodes (LN), and blood capillaries are included into the model as final accumulation compartments, to which mass is transferred via the airway route and the transepithelial path. Besides a basic version of the model describing the whole tracheobronchial region by one set of compartments, also an advanced approach is introduced which, in accordance with the International Commission on Radiation Protection (ICRP), subdivides the conducting airways into a bronchial (BB) and bronchiolar (bb) part. Preliminary results were generated with MS-Excel^(R) from deposition data of [email protected] median aerodynamic diameter (MMAD) particles, calculating local slow clearance fractions according to mathematical procedures introduced in previous publications. While mucociliary clearance is completely finished within 24h after exposure, slow clearance takes place in distinct phases and needs several days to weeks. This multi-stage event is also reflected in the respective retention curves which correspond well to previously published graphs.

A framework with capability of automatic generation of the human bronchial tree has been proposed.The proposed framework is developed based on Parametric Lindenmayer system (L-system).The structure is generated separately into the lung lobes with accurate geometry, taken from the CT Images.The generated bronchial tree can be used in phenomenological study of gas exchange. Background and objectiveThe human lungs exchange air with the external environment via the conducting airways. The application of an anatomically accurate model of the conducting airways can be helpful for simulating gas exchange and fluid distribution throughout the bronchial tree in the lung. MethodsIn the current study, Lindenmayer system (L-system) has been formulated to generate the bronchial tree structure in a human lung. It has been considered that the structure of the bronchial tree is divided into two main segments: 1) The central airways (from the trachea to segmental bronchi) and 2) the dichotomous structure (from segmental bronchi to terminal bronchioles). Two sets of parametric rewriting rules which can be used to develop central and peripheral airways have been proposed; the first set used to develop central airways consists of seven rules, while the second rule set contains four rules. ResultsThe proposed model is capable of generating bronchial tree inside the volume of the host lung; and comparison of the resulting model with those reported in the literature shows that the morphometric characteristics of L-system structure are in good agreement with their corresponding experimental data. ConclusionThe resulting model can be used to obtain a mathematical model required for the study of transport phenomena occurring in the lung during respiration.

This chapter focuses on the epithelium of the distal conducting airways, or bronchioles, with emphasis on the area of transition between conducting airways and the gas-exchange area. The bronchiolar region has a substantial variation from one species of mammal to the next. This variability includes the microenvironment in which epithelial cells are found, particularly the zone of transition between bronchiolar, non-gas exchange regions and the alveolar gas-exchange regions. There is also considerable interspecies variability in the general composition of the bronchiolar epithelium. The principal alterations involve the distribution, number, and percentage of the population that is nonciliated cells. In addition, there is substantial variability in the composition and differentiated expression of the nonciliated epithelial population in this region.

Using the nasal route to deliver pharmaceutical aerosols to the lungs has a number of advantages, including coadministration during noninvasive ventilation. The objective of this study was to evaluate the growth and deposition characteristics of nasally administered aerosol throughout the conducting airways based on delivery with streamlined interfaces implementing two forms of controlled condensational growth technology. Characteristic conducting airways were considered including a nose-mouth-throat (NMT) geometry, complete upper tracheobronchial (TB) model through the third bifurcation (B3), and stochastic individual path (SIP) model to the terminal bronchioles (B15). Previously developed streamlined nasal cannula interfaces were used for the delivery of submicrometer particles using either enhanced condensational growth (ECG) or excipient enhanced growth (EEG) techniques. Computational fluid dynamics (CFD) simulations predicted aerosol transport, growth, and deposition for a control (4.7 μm) and three submicrometer condensational aerosols with budesonide as a model insoluble drug. Depositional losses with condensational aerosols in the cannula and NMT were less than 5% of the initial dose, which represents an order-of-magnitude reduction compared to the control. The condensational growth techniques increased the TB dose by a factor of 1.1–2.6×, delivered at least 70% of the dose to the alveolar region, and produced final aerosol sizes ≥2.5 μm. Compared to multiple commercial orally inhaled products, the nose-to-lung delivery approach increased dose to the biologically important lower TB region by factors as large as 35×. In conclusion, nose-to-lung delivery with streamlined nasal cannulas and condensational aerosols was highly efficient and targeted deposition to the lower TB and alveolar regions. Copyright 2014 American Association for Aerosol Research

Predicting the amount of particle deposition in the human lung following exposure to airborne particulate matter is the first step toward evaluating risks associated with exposure to airborne pollutants. Realistic deposition models are needed for accurate predictions of deposition in the lung, but a major limitation is the degree to which the lung geometry can be accurately reconstructed. Morphometric data for the entire airway tree of the human lung are not available. So far, idealistic lung structures have been used for deposition calculations. In this study, 10 statistical lung structures based on morphometric measurements of Raabe et al. (1976) were generated for the conducting airways of the human lung. A symmetric, dichotomous branching alveolar airway structure was attached to the end of the conducting airway tree of each lung structure. The total volume of the alveolar region was the same among the lung geometries. Using a mathematical scheme developed previously (Anjilvel and Asgharian 1995), reg...

An anatomically accurate model of the conducting airways is essential for adequately simulating gas mixing, particle deposition, heat and water transfer, and fluid distribution. We have extended a two-dimensional tree-growing algorithm to three dimensions for generation of a host-shape dependent three-dimensional conducting airway model. Terminal branches in the model are both length limited and volume-supplied limited. A limit is imposed on the maximum possible branch angle between a daughter and parent branch. Comparison of the resulting model with morphometric data shows that the algorithm produces branching and length ratios, path lengths, numbers of branches, and branching angles very close to those from the experimental data. The correlation between statistics from the generated model and those from morphometric studies suggests that the conducting airway structure can be described adequately using a “supply and demand” algorithm. The resulting model is a computational mesh that can be used for simulating transport phenomena. © 2000 Biomedical Engineering Society.

A technique is described for high-resolution measurement of aerosol deposition patterns in the conducting airways, using a fluorescently labelled aerosol in an isolated lung preparation. Results are presented for the deposition of a micron-sized aerosol in the porcine lung. The deposition distributions in the neighbourhood of a number of large bronchial bifurcations are reconstructed from serial sections. The deposition pattern is found to be extremely inhomogeneous, with the highest concentrations typically occurring in localised “hot spots” near the carinal ridge. There is also a great deal of variability in deposition between different bifurcations. The relationship with previous experimental and theoretical work and some possible physiological implications are discussed.