Airway Cast Research Articles

An atypical airway cast.

A 60-year-old man intubated for airway protection after smoke inhalation was found to have decompensated hypercapnic respiratory failure. Fiberoptic bronchoscopy revealed obstructive airway slough and pseudomembrane, a manifestation of severe inhalation injury. Veno-venous extracorporeal membrane oxygenation was established for stabilization. The airway casts were removed successfully with periprocedural veno-venous extracorporeal membrane oxygenation support.

In Vitro Model for Analysis of High-Flow Aerosol Delivery During Continuous Nebulization.

To understand the fate of aerosols delivered by high-flow nasal cannula using continuous nebulization, an open-source anatomical model was developed and validated with a modified real-time gamma ratemeter technique. Mass balance defined circuit losses. Responsiveness to infusion rate and device technology were tested. A nasal airway cast derived from a computed tomography scan was converted to a 3-dimensional-printed head and face structure connected to a piston ventilator (breathing frequency 30 breaths/min, tidal volume 750 mL, duty cycle 0.50). For mass balance experiments, saline mixed with Technetium-99m was infused for 1 h. Aerosol delivery was measured using a gamma ratemeter oriented to an inhaled mass filter at the hypopharynx of the model. Background and dead-space effects were minimized. All components were imaged by scintigraphy. Continuous nebulization was tested at infusion rates of 10-40 mL/h with gas flow of 60 L/min using a breath-enhanced jet nebulizer (BEJN), and a vibrating mesh nebulizer. Drug delivery rates were defined by the slope of ratemeter counts/min (CPM/min) versus time (min). The major source of aerosol loss was at the nasal interface (∼25%). Significant differences in deposition on circuit components were seen between nebulizers. The nebulizer residual was higher for BEJN (P = .006), and circuit losses, including the humidifier, were higher for vibrating mesh nebulizer (P = .006). There were no differences in delivery to the filter and head model. For 60 L/min gas flow, as infusion pump flow was increased, the rate of aerosol delivery (CPM/min) increased, for BEJN from 338 to 8,111; for vibrating mesh nebulizer, maximum delivery was 2,828. The model defined sites of aerosol losses during continuous nebulization and provided a realistic in vitro system for testing aerosol delivery during continuous nebulization. Real-time analysis can quantify effects of multiple changes in variables (nebulizer technology, infusion rate, gas flow, and ventilation) during a given experiment.

Fibrin airway cast obstruction: Experience, classification, and treatment guideline from Denver.

Plastic bronchitis (PB) is a condition characterized by the formation of thick airway casts leading to acute and often life-threatening airway obstruction. PB occurs mainly in pediatric patients with congenital heart disease (CHO) who have undergone staged surgical palliation (Glenn, Fontan), but can also occur after chemical inhalation, H1N1, severe COVID-19, sickle cell disease, severe asthma, and other diseases. Mortality risk from PB can be up to 40%-60%, and no treatment guidelineexist. The objectives herein are to develop a standardized evaluation, classification, and treatment guideline for PB patients presenting with tracheobronchial casts, based on our experience with PB at the Children's Hospital of Colorado in Denver. We describe 11 patients with CHO-associated PB (post-Fontan [n = 9], pre-Fontan [n = 2]) who presented with their initial episodes. We utilized histopathological analysis of tracheobronchial casts to guide treatment in these patients, utilizing our hospital-wide guideline document and classification system. We found that 100% of post-Fontan PB patients had fibrinous airway casts, while pre-Fontan PB casts were fibrinous only in one of two patients (50%). Utilizing histopathology as a guide to therapy, PB patients with fibrin airway casts were treated with airway-delivered fibrinolytics and anticoagulants, as well as aggressive airway clearance and other supportive care measures. These therapies resulted in successful cast resolution and improved survival in post-Fontan PB patients. We have shown an improved outcome in PB patients whose treatment plan was based on Denver's PB classification schema and standardized treatment guidelinebased on tracheobronchial cast histopathology.

Inhalational Injury Management: From Intubation to Nebulized Heparin

Inhalational injury is common during fire accidents. Upper airway injury occurs due to heat, whereas the lower airway injury is caused by chemical irritation. It causes local damage to the upper, lower airway, and lung parenchyma leading to erythema, bronchorrhea, edema, airway obstruction, and surfactant loss. Plasma leakage occurs due to a storm of pro-inflammatory markers and vascular leak, with fibrin deposition, leading to formation of airway cast and debris increasing the risk of airway obstruction. Systemic complications occur due to anoxia, carbon monoxide, and hydrogen cyanide poisoning. An inhalational injury should be suspected in patients with a history of exposure to flames and in those who are entrapped in a closed compartment during the fire. Facial burns, singed facial or nasal hair, stridor, and carbonaceous sputum should raise suspicion of high index of inhalational injury. Severity of inhalational injury can be graded using 133 Xenon (radioisotope) study, bronchoscopy, computerized tomography findings, or virtual endoscopy. In the management of inhalational injury, keeping airway patent and secured is of vital importance. According to the advanced trauma life support principles, these patients should be intubated early, but as per the recent literature, it may not be necessary to intubate all inhalation injury patients. Adjuvant therapy includes bronchodilators, mucolytics, and beta-agonists. Nebulized heparin is found to be useful as it breaks and prevents new clot formations in the airway without any systemic anticoagulant effects. Inhalational injury is an independent risk factor for increase in mortality in burn patients.

Plastic bronchitis in a 6-year-old boy: An unusual indication for rigid bronchoscopy

Plastic bronchitis (PB) is an extremely rare clinical entity where inspissated cast is found in endobronchial airway leading to respiratory distress. It is a large gelatinous or rigid branching airway cast. Removal of this endobronchial cast rapidly improves this condition. The underlying causes for this PB are pulmonary diseases, congenital heart disease, and few other conditions. The treatment of this condition includes rigid bronchoscopy and removal of this cast. Here, we present a case of PB in a previously healthy 6-year-old boy presenting with respiratory distress. This child was managed by rigid bronchoscopy and this cast was removed from the right bronchus.

Does upper airway deformation affect drug deposition?

Knowledge that enables the accurate simulation of drug deposition in the human upper airway is necessary to develop robust platforms for efficient drug delivery by inhalation devices. The human upper airway is deformable during inhalation but how it could affect the deposition of inhaled drugs is unknown. We aimed to determine whether pharyngeal deformation at the soft palate level would have any significant effects on throat deposition, in vitro lung dose and fine particle fraction. In this study, dry mannitol powders were delivered to the next-generation cascade impactor (NGI) through the United States Pharmacopeia (USP) throat, and a realistic upper airway cast (RUPAC) at flow rates of 40, 60 and 80 L min-1. Deformation of the upper airway at 25%, 50%, and 75% in the lateral and antero-posterior directions were experimentally simulated in the RUPAC. Throat deposition (p = 0.04) is significantly affected when the upper airway deforms laterally but not antero-posteriorly.

PLASTIC BRONCHITIS MIMICKING WITH FOREIGN BODY BRONCHUS IN PEDIATRIC PATIENT – A REVIEW

Plastic bronchitis (PB) is an extremely rare clinical entity in pediatric age group where an inspissated cast is found in endobronchial airway leading to respiratory distress. It is a large gelatinous or rigid branching airway cast which can lead to life-threatening episodes. The underlying causes for this PB are pulmonary diseases, congenital heart disease (CHD), and a few other conditions. The endobronchial casts are classified into inflammatory and acellular types. Inflammatory casts are most commonly found in primary lung disease, whereas acellular casts are frequently seen in patients with CHD. Removal of this endobronchial cast rapidly improves this condition. Bronchoscopy with bronchial lavage is considered as the gold standard treatment of PB. The patient is managed by rigid bronchoscopy and removal of this cast from bronchus is like foreign body removal from the tracheobronchial tree. Clinicians should have knowledge for correct diagnosis and treatment of PB. This review article discusses about etiopathology, epidemiology, clinical presentations, and diagnosis and treatment of PB among pediatric patients.

From the Cover: Catalytic Antioxidant Rescue of Inhaled Sulfur Mustard Toxicity.

Sulfur mustard (bis 2-chloroethyl ethyl sulfide, SM) is a powerful bi-functional vesicating chemical warfare agent. SM tissue injury is partially mediated by the overproduction of reactive oxygen species resulting in oxidative stress. We hypothesized that using a catalytic antioxidant (AEOL 10150) to alleviate oxidative stress and secondary inflammation following exposure to SM would attenuate the toxic effects of SM inhalation. Adult male rats were intubated and exposed to SM (1.4 mg/kg), a dose that produces an LD50 at approximately 24 h. Rats were randomized and treated via subcutaneous injection with either sterile PBS or AEOL 10150 (5 mg/kg, sc, every 4 h) beginning 1 h post-SM exposure. Rats were euthanized between 6 and 48 h after exposure to SM and survival and markers of injury were determined. Catalytic antioxidant treatment improved survival after SM inhalation in a dose-dependent manner, up to 52% over SM PBS at 48 h post-exposure. This improvement was sustained for at least 72 h after SM exposure when treatments were stopped after 48 h. Non-invasive monitoring throughout the duration of the studies also revealed blood oxygen saturations were improved by 10% and clinical scores were reduced by 57% after SM exposure in the catalytic antioxidant treatment group. Tissue analysis showed catalytic antioxidant therapy was able to decrease airway cast formation by 69% at 48 h post-exposure. To investigate antioxidant induced changes at the peak of injury, several biomarkers of oxidative stress and inflammation were evaluated at 24 h post-exposure. AEOL 10150 attenuated SM-mediated lung lipid oxidation, nitrosative stress and many proinflammatory cytokines. The findings indicate that catalytic antioxidants may be useful medical countermeasure against inhaled SM exposure.

Sulfur mustard inhalation: mechanisms of injury, alteration of coagulation, and fibrinolytic therapy.

Acute lung injury due to sulfur mustard (SM) inhalation causes the formation of airway fibrin casts that obstruct airways at multiple levels, leading to acute respiratory failure and death. These pathophysiological effects are seen in rodent models of acute SM vapor inhalation, as well as in human victims of acute SM inhalation. In rat models, the initial steps in activation of the coagulation system at extravascular sites depend on tissue factor (TF) expression by airway cells, especially in the microparticle fraction, and these effects can be inhibited by TF pathway inhibitor protein. Not only does the procoagulant environment of the acutely injured lung contribute to airway cast formation, but these lesions persist in airways because of the activation of multiple antifibrinolytic pathways, including plasminogen activator inhibitor-1, thrombin-activatable fibrinolysis inhibitor, and α2-antiplasmin. Airway administration of tissue plasminogen activator can overwhelm these effects and save lives by preventing fibrin-dependent airway obstruction, gas-exchange abnormalities, and respiratory failure. In human survivors of SM inhalation, fibrotic processes, including bronchiolitis obliterans and interstitial fibrosis of the lung, are among the most disabling chronic lesions. Antifibrotic therapies may prove useful in preventing either or both of these forms of chronic lung damage.

Preparation of low cost bronchopulmonary airway cast

IntroductionThe study of tracheo-bronchial branching pattern and formation of bronchopulmonary segments is of great importance in understanding lung anatomy and physiology. While teaching this subject to first year medical students, teachers often take help of atlases and digital images. Preparation of a cast of tracheo-bronchial airways would be of great help to make the students understand the three-dimensional branching and relation between various segments of lungs and thus to better understand pulmonary anatomy. Materials and methodsThis article discusses a simple and very low cost method of preparation of bronchopulmonary airway cast by using LAPOX™ Epoxy resin and a goat lung which are comparatively cheaper and easily available. Results and conclusionMany different methods and materials are described in textbooks for the preparation of tracheo-bronchial casts. This method can be employed in institutes where major funding for better advanced methods are unavailable or for students themselves as a method of self-study.

Non-uniform central airways ventilation model based on vascular segmentation

Improvements in the understanding of the physiology of the central airways require an appropriate representation of the non-uniform ventilation at its terminal branches. This paper proposes a new technique for estimating the non-uniform ventilation at the terminal branches by modelling the volume change of their distal peripheral airways, based on vascular segmentation. The vascular tree is used for sectioning the dynamic CT-based 3D volume of the lung at 11 time points over the breathing cycle of a research animal. Based on the mechanical coupling between the vascular tree and the remaining lung tissues, the volume change of each individual lung segment over the breathing cycle was used to estimate the non-uniform ventilation of its associated terminal branch. The 3D lung sectioning technique was validated on an airway cast model of the same animal pruned to represent the truncated dynamic CT based airway geometry. The results showed that the 3D lung sectioning technique was able to estimate the volume of the missing peripheral airways within a tolerance of 2%. In addition, the time-varying non-uniform ventilation distribution predicted by the proposed sectioning technique was validated against CT measurements of lobar ventilation and showed good agreement. This significant modelling advance can be used to estimate subject-specific non-uniform boundary conditions to obtain subject-specific numerical models of the central airway flow.

Airway tissue plasminogen activator prevents acute mortality due to lethal sulfur mustard inhalation.

Sulfur mustard (SM) is a chemical weapon stockpiled today in volatile regions of the world. SM inhalation causes a life-threatening airway injury characterized by airway obstruction from fibrin casts, which can lead to respiratory failure and death. Mortality in those requiring intubation is more than 80%. No therapy exists to prevent mortality after SM exposure. Our previous work using the less toxic analog of SM, 2-chloroethyl ethyl sulfide, identified tissue plasminogen activator (tPA) an effective rescue therapy for airway cast obstruction (Veress, L. A., Hendry-Hofer, T. B., Loader, J. E., Rioux, J. S., Garlick, R. B., and White, C. W. (2013). Tissue plasminogen activator prevents mortality from sulfur mustard analog-induced airway obstruction. Am. J. Respir. Cell Mol. Biol. 48, 439-447). It is not known if exposure to neat SM vapor, the primary agent used in chemical warfare, will also cause death due to airway casts, and if tPA could be used to improve outcome. Adult rats were exposed to SM, and when oxygen saturation reached less than 85% (median: 6.5 h), intratracheal tPA or placebo was given under isoflurane anesthesia every 4 h for 48 h. Oxygen saturation, clinical distress, and arterial blood gases were assessed. Microdissection was done to assess airway obstruction by casts. Intratracheal tPA treatment eliminated mortality (0% at 48 h) and greatly improved morbidity after lethal SM inhalation (100% death in controls). tPA normalized SM-associated hypoxemia, hypercarbia, and lactic acidosis, and improved respiratory distress. Moreover, tPA treatment resulted in greatly diminished airway casts, preventing respiratory failure from airway obstruction. tPA given via airway more than 6 h after exposure prevented death from lethal SM inhalation, and normalized oxygenation and ventilation defects, thereby rescuing from respiratory distress and failure. Intra-airway tPA should be considered as a life-saving rescue therapy after a significant SM inhalation exposure incident.

Intratracheal heparin improves plastic bronchitis due to sulfur mustard analog

Inhalation of sulfur mustard (SM) and SM analog, 2-chloroethyl ethyl sulfide (CEES), cause fibrinous cast formation that occludes the conducting airways, similar to children with Fontan physiology-induced plastic bronchitis. These airway casts cause significant mortality and morbidity, including hypoxemia and respiratory distress. Our hypothesis was that intratracheal heparin, a highly cost effective and easily preserved rescue therapy, could reverse morbidity and mortality induced by bronchial cast formation. Sprague-Dawley rats were exposed to 7.5% CEES via nose-only aerosol inhalation to produce extensive cast formation and mortality. The rats were distributed into three groups: non-treated, phosphate-buffered saline (PBS)-treated, and heparin-treated groups. Morbidity was assessed with oxygen saturations and clinical distress. Blood and bronchoalveolar lavage fluid (BALF) were obtained for analysis, and lungs were fixed for airway microdissection to quantify the extent of airway cast formation. Heparin, given intratracheally, improved survival (100%) when compared to non-treated (75%) and PBS-treated (90%) controls. Heparin-treated rats also had improved oxygen saturations, clinical distress and airway cast scores. Heparin-treated rats had increased thrombin clotting times, factor Xa inhibition and activated partial thromboplastin times, indicating systemic absorption of heparin. There were also increased red blood cells (RBCs) in the BALF in 2/6 heparin-treated rats compared to PBS-treated control rats. Intratracheal heparin 1 hr after CEES inhalation improved survival, oxygenation, airway obstruction, and clinical distress. There was systemic absorption of heparin in rats treated intratracheally. Some rats had increased RBCs in BALF, suggesting a potential for intrapulmonary bleeding if used chronically after SM inhalation.

Tissue factor pathway inhibitor prevents airway obstruction, respiratory failure and death due to sulfur mustard analog inhalation

Sulfur mustard (SM) inhalation causes airway injury, with enhanced vascular permeability, coagulation, and airway obstruction. The objective of this study was to determine whether recombinant tissue factor pathway inhibitor (TFPI) could inhibit this pathogenic sequence. MethodsRats were exposed to the SM analog 2-chloroethyl ethyl sulfide (CEES) via nose-only aerosol inhalation. One hour later, TFPI (1.5mg/kg) in vehicle, or vehicle alone, was instilled into the trachea. Arterial O2 saturation was monitored using pulse oximetry. Twelve hours after exposure, animals were euthanized and bronchoalveolar lavage fluid (BALF) and plasma were analyzed for prothrombin, thrombin–antithrombin complex (TAT), active plasminogen activator inhibitor-1 (PAI-1) levels, and fluid fibrinolytic capacity. Lung steady-state PAI-1 mRNA was measured by RT-PCR analysis. Airway-capillary leak was estimated by BALF protein and IgM, and by pleural fluid measurement. In additional animals, airway cast formation was assessed by microdissection and immunohistochemical detection of airway fibrin. ResultsAirway obstruction in the form of fibrin-containing casts was evident in central conducting airways of rats receiving CEES. TFPI decreased cast formation, and limited severe hypoxemia. Findings of reduced prothrombin consumption, and lower TAT complexes in BALF, demonstrated that TFPI acted to limit thrombin activation in airways. TFPI, however, did not appreciably affect CEES-induced airway protein leak, PAI-1 mRNA induction, or inhibition of the fibrinolytic activity present in airway surface liquid. ConclusionsIntratracheal administration of TFPI limits airway obstruction, improves gas exchange, and prevents mortality in rats with sulfur mustard-analog-induced acute lung injury.

Immunophenotyping and Protein Profiling of Fontan-associated Plastic Bronchitis Airway Casts

Plastic bronchitis (PB) is a rare and deadly condition that is characterized by the formation of airway casts. It most frequently occurs in children with underlying congenital heart disease that has been surgically palliated by the Fontan procedure. The Fontan circulation results in above-normal central venous pressure, and it has been hypothesized that the formation of airway casts is due to lymph leak. Knowledge of plastic bronchitis pathogenesis is poor and stems mostly from published case reports. To garner information about cast pathogenesis by characterizing inflammatory cell phenotypes in existing formalin-preserved, paraffin-embedded samples and generating protein and cytokine-chemokine profiles of airway cast homogenates. We used immunofluorescence confocal microscopy, state-of-the-science proteomics, and a cytokine array assay to immunophenotype cellular content and to generate protein and cytokine profiles of plastic bronchitis airway casts, respectively. Neutrophils, eosinophils, macrophages, and B lymphocytes were identified in cast samples; there were notably fewer T lymphocytes. Fibrin(ogen) was an abundant protein in the cast proteome. Histone H4 was also abundant, and immunofluorescence microscopy demonstrated it to be mostly extracellular. The cytokine profile of plastic bronchitis casts was proinflammatory. Plastic bronchitis airway casts from children with Fontan physiology are composed of fibrin and are cellular and inflammatory in nature, providing evidence that their formation cannot be explained simply by lymph leak into the airways. Consequences of cellular necrosis including extracellular histones and the apparent low number of T cells indicate that a derangement in inflammation resolution likely contributes to cast formation.

Plastic Bronchitis in an Adult with Asthma

Plastic bronchitis is a rare disease characterized by marked airway obstruction, via the formation of large gelatinous or rigid airway cast. In Korea, there were a few case reports with plastic bronchitis not in adults, but in children. So we report a case of an adult who was diagnosed as plastic bronchitis with eosinophilic casts, with no history of atopic and cardiac disease.

Inspiratory and expiratory aerosol deposition in the upper airway

Aerosol deposition efficiency (DE) in the extrathoracic airways during mouth breathing is currently documented only for the inspiratory phase of respiration, and there is a need for quantification of expiratory DE. Our aim was to study both inspiratory and expiratory DE in a realistic upper airway geometry. This was done experimentally on a physical upper airway cast by scintigraphy, and numerically by computational fluid dynamic simulations using a Reynolds Averaged Navier–Stokes (RANS) method with a k-ω SST turbulence model coupled with a stochastic Lagrangian approach. Experiments and simulations were carried out for particle sizes (3 and 6 µm) and flow rates (30 and 60 L/min) spanning the ranges of Stokes (Stk) and Reynolds (Re) number pertinent to therapeutic and environmental aerosols. We showed that inspiratory total deposition data obtained by scintigraphy fell onto a previously published deposition curve representative of a range of upper airway geometries. We also found that expiratory and inspiratory DE curves were almost identical. Finally, DE in different compartments of the upper airway model showed a very different distribution pattern of aerosol deposition during inspiration and expiration, with preferential deposition in oral and pharyngeal compartments, respectively. These compartmental deposition patterns were very consistent and only slightly dependent on particle size or flow rate. Total deposition for inspiration and expiration was reasonably well-mimicked by the RANS simulation method we employed, and more convincingly so in the upper range of the Stk and Re number. However, compartmental deposition patterns showed discrepancies between experiments and RANS simulations, particularly during expiration.

Impact of bronchial circulation on bronchial exudates following combined burn and smoke inhalation injury in sheep

We previously reported bronchial circulation contributes to pulmonary edema and increases shunt fraction following smoke inhalation, and bronchial blood flow significantly increases in inhalation injury. We hypothesized reduction of bronchial blood flow reduces exudation to the airway and ameliorates lung injury from combined burn and smoke insults (B&S injury). Method Merino ewes ( n = 28) randomly divided into three groups: (1) bronchial artery ligated and injured (injury + ligation group); (2) bronchial artery left intact and injured (injury + no ligation group); (3) bronchial artery ligated but not injured (no injury + ligation group) were subjected to a flame burn and inhalation injury under halothane anesthesia. Parameters were analyzed using Scheffe's post hoc test ( P < 0.05). All Groups were resuscitated with Ringer lactate solution and placed on a ventilator for 48 h. Results Pulmonary gas exchange (PaO 2/FiO 2) improved in injury + ligation group. Further, obstruction score, an index of airway cast formation, significantly changed between injury + no ligation group compared to both ligation groups. Conclusion Bronchial circulation plays a significant role in lung injury after B&S injury, and reduction of bronchial blood flow by bronchial artery ligation reduces bronchial exudates, resulting in improved gas exchange.

High resolution lung airway cast segmentation with proper topology suitable for computational fluid dynamic simulations

Developing detailed lung airway models is an important step towards understanding the respiratory system. While modern imaging and airway casting approaches have dramatically improved the potential detail of such models, challenges have arisen in image processing as the demand for greater detail pushes the image processing approaches to their limits. Airway segmentations with proper topology have neither loops nor invalid voxel-to-voxel connections. Here we describe a new technique for segmenting airways with proper topology and apply the approach to an image volume generated by magnetic resonance imaging of a silicone cast created from an excised monkey lung.

Bronchial Casts and Pandemic (H1N1) 2009 Virus Infection

Bronchial Casts and Pandemic (H1N1) 2009 Virus Infection