Large Airways Research Articles

Effect of radiological extent and severity of bronchiectasis on pulmonary function

Background: The aim of this study was to ascertain the effect of the extent and severity of bronchiectasis as determined with high-resolution computed tomography (HRCT) on lung function in patients with pure bronchiectasis, bronchiectasis and asthma, and bronchiectasis and chronic obstructive pulmonary disease (COPD).
 Methods: One hundred nineteen patients (71 with pure bronchiectasis, 25 asthmatic patients with bronchiectasis, and 23 COPD patients with bronchiectasis) underwent HRCT and pulmonary function tests. Computed tomography features were scored by the consensus of 2 radiologists.
 Results: There were no statistically significant differences among the 3 patient groups regarding the extent of bronchiectasis, bronchial dilatation degree, bronchial wall thickening, decreased attenuation in the lung parenchyma, or presence of mucus in the large and small airways. In the pure bronchiectasis group, a negative correlation was found between forced vital capacity (FVC) % of predicted, forced expiratory volume in 1 sec (FEV1) % of predicted, the FEV1/FVC ratio and the extent of bronchiectasis, bronchial wall thickening, bronchial wall dilatation, and decreased attenuation. At multivariate analysis the main morphologic changes associated with impairment of FVC and FEV1 were the extent of bronchiectasis and a decreased attenuation in the lung parenchyma. The decrease in the FEV1/FVC ratio was associated with bronchial wall dilatation. No correlation was found between morphologic changes and indices of pulmonary function in the asthma and COPD patients.
 Conclusions: Morphologic changes associated with bronchiectasis do not influence lung function in patients with asthma and COPD directly, although they do play a role in impairing pulmonary function in patients with bronchiectasis alone.

Maintenance of Deep Lung Architecture and Automated Airway Segmentation for 3D Mass Spectrometry Imaging

Mass spectrometry imaging (MSI) is a technique for mapping the spatial distributions of molecules in sectioned tissue. Histology-preserving tissue preparation methods are central to successful MSI studies. Common fixation methods, used to preserve tissue morphology, can result in artifacts in the resulting MSI experiment including delocalization of analytes, altered adduct profiles, and loss of key analytes due to irreversible cross-linking and diffusion. This is especially troublesome in lung and airway samples, in which histology and morphology is best interpreted from 3D reconstruction, requiring the large and small airways to remain inflated during analysis. Here, we developed an MSI-compatible inflation containing as few exogenous components as possible, forgoing perfusion, fixation, and addition of salt solutions upon inflation that resulted in an ungapped 3D molecular reconstruction through more than 300 microns. We characterized a series of polyunsaturated phospholipids (PUFA-PLs), specifically phosphatidylinositol (-PI) lipids linked to lethal inflammation in bacterial infection and mapped them in serial sections of inflated mouse lung. PUFA-PIs were identified using spatial lipidomics and determined to be determinant markers of major airway features using unsupervised hierarchical clustering. Deep lung architecture was preserved using this inflation approach and the resulting sections are compatible with multiple MSI modalities, automated interpretation software, and serial 3D reconstruction.

Altered generation of ciliated cells in chronic obstructive pulmonary disease

In COPD, epithelial changes are prominent features in the airways, such as goblet cell hyperplasia and squamous metaplasia. In contrast, it remains unclear whether ciliated cells are reduced and which pathways dysregulate epithelial differentiation. We hypothesized that bronchial epithelial cell lineage specification is dysregulated in COPD because of an aberrant reprogramming through transforming growth factor (TGF)-β1. Surgical lung tissue from 81 COPD and 61 control (smokers and non-smokers) patients was assessed for bronchial epithelial cell phenotyping by immunohistochemistry, both in situ and in vitro in reconstituted air-liquid interface (ALI) cultures. The role of TGF-β1 was studied in vitro. COPD epithelium in large airways, when compared to controls, showed decreased β-tubulin IV + ciliated cells (4.4%, 2.5–8.8% versus 8.5%, 6.3–11.8% of surface staining, median and IQR, p = 0.0009) and increased MUC5AC + goblet cells (34.8%, 24.4–41.9% versus 10.3%, 5.1–17.6%, p < 0.0001). Both features were recapitulated in the ALI-cultured epithelium from COPD patients. Exogenous TGF-β1 reduced mucociliary differentiation while neutralizing TGF-β1 during ALI increased both specialized cell types. The COPD airway epithelium displays altered differentiation for ciliated cells, which recapitulates in vitro, at least in part through TGF-β1.

Exercise fitness at 14 years: Good news for antenatal corticosteroids

The lungs of infants born with very low birth weight (VLBW) are not normal at term, even without a history of prematurity associated lung disease. Their lungs can continue to remodel for perhaps 20 years to be functionally close to normal, but the effects of aging on the previously preterm lung remain essentially unknown. Lung function of infants born at normal term can be categorized into quartiles from lower to higher function. Remarkably, the children, and subsequently the adults, track within each quartile to at least 30 years of age. And the lowest quartile has increased risk of asthma and chronic obstructive lung disease as adults. Virtually nothing is known about how the lung function of infants born preterm tracks across age. However, in early childhood, infants born preterm with a history of bronchopulmonary dysplasia (BPD) have several overlapping phenotypes that include large airway malacia, small airway disease, and parenchymal (alveolar and vascular) abnormalities. This mix of abnormalities likely also are present to lesser degrees in infants born VLBW without BPD. Within this context of respiratory outcomes in infants with VLBW, Nixon et al report that antenatal corticosteroid (ACS) use in a cohort of 14-year-old children improved peak oxygen uptake with maximal exercise in non-black males relative to black males or females. This result correlated with greater physical activity in non-black males. The result was contrary to their hypothesis that ACS would decrease exercise tolerance because ACS inhibit alveolar and vascular development in the premature lung. My concern is that the % predicted peak oxygen uptake values were 85 ± 19% for ACS exposed and 78 ± 19% for ACS unexposed children born VLBW. These children thus are in the lowest quartile for normal lung function. There must be concerns for how these lungs will age. At least ACS did not seem to aggravate the problem. Article page 98▸ Antenatal Steroid Exposure, Aerobic Fitness, and Physical Activity in Adolescents Born Preterm with Very Low Birth WeightThe Journal of PediatricsVol. 215PreviewTo determine whether antenatal corticosteroid exposure is associated with aerobic fitness or physical activity participation in adolescents born preterm with very low birth weight (VLBW). Full-Text PDF

Lung eosinophils increase vagus nerve-mediated airway reflex bronchoconstriction in mice.

Eosinophils mediate airway hyperresponsiveness by increasing vagally mediated reflex bronchoconstriction. Here, we tested whether circulating or airway eosinophils change nerve function. Airway resistance in response to aerosolized 5-hydroxytryptamine (5-HT, 10-300 mM) was measured in wild-type mice or transgenic mice that overexpress IL5 in T cells (+IL5T), overexpress IL5 in airway epithelium (+IL5AE), or overexpress IL5 but are devoid of eosinophils (+IL5AE/-Eos). Inflammatory cells in bronchoalveolar lavage (BAL), blood, and bone marrow were quantified. Blood eosinophils were increased in +IL5T and +IL5AE mice compared with wild-type mice. +IL5T mice had increased eosinophils in bone marrow while +IL5AE mice had increased eosinophils in BAL. Eosinophils surrounding large airways were significantly increased only in +IL5AE mice. With intact vagal innervation, aerosolized 5-HT significantly increased airway resistance in +IL5AE mice. 5-HT-induced bronchoconstriction was blocked by vagotomy or atropine, demonstrating that it was mediated via a vagal reflex. Airway resistance was not increased in +IL5AE/-Eos mice, demonstrating that it required lung eosinophils, but was not affected by increased bone marrow or blood eosinophils or by increased IL5 in the absence of eosinophils. Eosinophils did not change M3 function on airway smooth muscle, since airway responses to methacholine in vagotomized mice were not different among strains. Eosinophils surrounding large airways were sufficient, even in the absence of increased IL5 or external insult, to increase vagally mediated reflex bronchoconstriction. Specifically blocking or reducing eosinophils surrounding large airways may effectively inhibit reflex hyperresponsiveness mediated by vagus nerves in eosinophilic asthma.

Endobronchial aspergilloma-a comprehensive literature review with focus on diagnosis and treatment modalities.

Endobronchial aspergilloma (EBA) is a rare manifestation of pulmonary infection with Aspergillus spp. Comprised of hyphae, mucus, and cellular debris, the massive fungus overgrowth can lead to obstructive pneumonitis in large airways, manifesting as cough, dyspnea, hemoptysis, or weight loss. The aim of this paper is to review the literature on endobronchial aspergilloma to further elucidate this disease entity and to classify it as a non-invasive form of pulmonary aspergillosis. A descriptive analysis was performed on articles on PubMed database that contained the key word "endobronchial aspergilloma." A total of 28 cases were obtained. Four articles were excluded as they were not available in the English format. Although EBA is extremely rare, it should be considered in the differential diagnosis of endobronchial masses in immunocompromised patients. There is a potential for the disease entity to progress to tracheobronchitis and fulminant respiratory failure. As such, early detection with bronchoscopy, biopsy, and culture is required to confirm pulmonary aspergillosis. Current treatment regimens remain to be optimized, though piecemeal resection of the mycetoma with bronchoscopic techniques with the addition of systemic antifungals and their combinations has been reported as efficacious.

Impulse Oscillometry to Evaluate Lung Function in Young Children Under Five Years with Sickle Cell Disease

BACKGROUND Young children with sickle cell disease (SCD) aged 2 - 5 years old are at the highest risk of acute chest syndrome (ACS), a leading cause of morbidity and mortality. In addition to severe forms of SCD (HbSS and HbSβ0 thalassemia), asthma and airway hyper-responsiveness are also known risk factors for ACS, and are three to five times more prevalent in older children and adults with SCD. However in SCD children under 5 years there are only a few studies describing airway function, due to limitations in spirometry and other common pulmonary function tests (PFTs). Impulse oscillometry, a passive, non-invasive technique to evaluate airway function via pulmonary resistance and reactance, has been validated in children as young as 3 years, but has not been used widely in children with SCD. OBJECTIVE We sought to describe baseline airway function in children under 5 years with SCD using impulse oscillometry, as part of an ongoing observational study to evaluate lung function in young SCD children over time. METHOD Following IRB approval, participation in the ongoing prospective study was offered to patients aged 3 - 5 years old with HbSS and HbSβ0 thalassemia followed at the Pediatric Sickle Cell Clinic at Augusta University. Parents of the consented patients completed a modified ISAAC questionnaire assessing reported asthma symptoms and tobacco smoke exposure. Baseline IOS was obtained within 6 months of consent, with other clinical data obtained from medical records. Airway function was assessed using airway resistance at 5Hz and 20Hz (R5, R20), and reactance at 5Hz (X5). Percent predicted values were computed using NHANES (National Health and Nutrition Examination Survey) reference criteria for age, height, gender and ethnicity. RESULTS Out of 9 consented patients, 7 completed the ISAAC questionnaire and 6 successfully performed IOS. One patient consented but deferred participation to next visit and 1 patient with HbSC was excluded from analysis. All remaining patients had sickle cell anemia (HbSS). Age range at study enrolment was 3.7 - 5.4 years (mean 4.6 years). All participants were African American, 4/7 were male. Four out of 7 survey participants were already on Hydroxyurea therapy for their disease with therapy duration ranging from 2 - 41 months. None had preceding history of ACS. One survey respondent reported asthma symptoms (wheezing, dry cough at night) in preceding 12 months and 1 reported passive tobacco exposure. None reported a prior asthma diagnosis. Of the 6 participants with PFT data, baseline percent-predicted values for IOS parameters R5 and R20 were 114.83 ± 22.37 and 97.83 ± 23.11 respectively. Baseline X5 (%pred) was 76.33 ± 48.59. DISCUSSION Our preliminary results show normal baseline airway function in this subset of young SCA patients, with R5 representing total airway resistance, and R20 representing resistance in large airways. Small airway function can be deduced from differences between R5 and R20. Airway resistance decreases with age, and early changes in small airway resistance can be seen in children with asthma and obstructive symptoms. Low frequency reactance serves as a measure of airway distensibility, especially in the distal airways. Therefore, conditions affecting lung elasticity would result in abnormal X5. Ongoing data collection and follow-up will help us study how airway function evolves in young children with SCA with or without underlying asthma. We will also assess the effects of Hydroxyurea and other disease-modifying therapies on airway function over time. Disclosures No relevant conflicts of interest to declare.

Three-dimensional modeling of human respiratory system for tasks of health risk assessment in the exposure to the chemicals inhalation

In the framework of multi-level model of accumulation of functional disorders in the human body under the influence of environmental factors there is delivered a sub-model of the “meso-level" of the respiratory system. The article is devoted to the three-dimensional modelling of the air flow in large airways of a human. The considered approaches can be applied for tasks of the health risk assessment in chemicals inhalation exposure.

Reactance and elastance as measures of small airways response to bronchodilator in asthma.

Bronchodilation alters both respiratory system resistance (Rrs) and reactance (Xrs) in asthma, but how changes in Rrs and Xrs compare, and respond differently in health and asthma, in reflecting the contributions from the large and small airways has not been assessed. We assessed reversibility using spirometry and oscillometry in healthy and asthma subjects. Using a multibranch airway-tree model with the mechanics of upper airway shunt, we compared the effects of airway dilation and small airways recruitment to explain the changes in Rrs and Xrs. Bronchodilator decreased Rrs by 23.0 (19.0)% in 18 asthma subjects and by 13.5 (19.5)% in 18 healthy subjects. Estimated respiratory system elastance (Ers) decreased by 23.2 (21.4)% in asthma, with no significant decrease in healthy subjects. With the use of the model, airway recruitment of 15% across a generation of the small airways could explain the changes in Ers in asthma with no recruitment in healthy subjects. In asthma, recruitment accounted for 40% of the changes in Rrs, with the remaining explained by airway dilation of 6.8% attributable largely to the central airways. Interestingly, the same dilation magnitude explained the changes in Rrs in healthy subjects. Shunt only affected Rrs of the model. Ers was unaltered in health and unaffected by shunt in both groups. In asthma, Ers changed comparably to Rrs and could be attributed to small airways, while the change in Rrs was split between large and small airways. This implies that in asthma Ers sensed through Xrs may be a more effective measure of small airways obstruction and recruitment than Rrs.NEW & NOTEWORTHY This is the first study to quantify to relative contributions of small and large airways to bronchodilator response in healthy subjects and patients with asthma. The response of the central airways to bronchodilator was similar in magnitude in both study groups, whereas the response of the small airways was significant among patients with asthma. These results suggest that low-frequency reactance and derived elastance are both sensitive measures of small airway function in asthma.

Fatty airways: implications for obstructive disease.

Epidemiological studies report that overweight or obese asthmatic subjects have more severe disease than those of a healthy weight. We postulated that accumulation of adipose tissue within the airway wall may occur in overweight patients and contribute to airway pathology. Our aim was to determine the relationship between adipose tissue within the airway wall and body mass index (BMI) in individuals with and without asthma.Transverse airway sections were sampled in a stratified manner from post mortem lungs of control subjects (n=15) and cases of nonfatal (n=21) and fatal (n=16) asthma. The relationship between airway adipose tissue, remodelling and inflammation was assessed. The areas of the airway wall and adipose tissue were estimated by point count and expressed as area per mm of basement membrane perimeter (Pbm). The number of eosinophils and neutrophils were expressed as area densities.BMI ranged from 15 to 45 kg·m-2 and was greater in nonfatal asthma cases (p<0.05). Adipose tissue was identified in the outer wall of large airways (Pbm >6 mm), but was rarely seen in small airways (Pbm <6 mm). Adipose tissue area correlated positively with eosinophils and neutrophils in fatal asthma (Pbm >12 mm, p<0.01), and with neutrophils in control subjects (Pbm >6 mm, p=0.04).These data show that adipose tissue is present within the airway wall and is related to BMI, wall thickness and the number of inflammatory cells. Therefore, the accumulation of airway adipose tissue in overweight individuals may contribute to airway pathophysiology.

Assessing small airways dysfunction in asthma, asthma remission and healthy controls using particles in exhaled air.

PExA mass can distinguish asthmatics from healthy individuals. Subjects with complete, but not clinical, asthma remission exhale more PExA mass compared to asthma. Higher PExA mass was associated with better function of both the small and large airways. http://bit.ly/2znHABg

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.

NOVEL CRYOBIOPSY TECHNIQUE USING A LONG ENDOBRONCHIAL TUBE TO PREVENT BLEEDING COMPLICATIONS

SESSION TITLE: Emerging Techniques for Interventional Pulmonary SESSION TYPE: Original Investigations PRESENTED ON: 10/20/2019 2:15 PM - 3:15 PM PURPOSE: Prophylactic balloon blockers are placed to prevent blood flooding into the large central airway during cryobiopsy. However, the blocker may interfere with, and increase the difficulty of, the cryobiopsy procedure. This study evaluated a novel and simple technique using a long silicone endobronchial tube as a drain for bleeding during cryobiopsy. METHODS: Under local anesthesia and moderate conscious sedation, a customized silicone tube (5.0 mm inner diameter, 40 or 48 cm in length) was advanced through the nose and trachea to the target bronchus under bronchoscopic control using a 4.0- or 4.2-mm thin bronchoscope and firmly wedged into the target bronchus to prevent blood leakage from the tube during the cryobiopsy. A forceps biopsy was performed followed by a cryobiopsy using a 1.9-mm cryoprobe through the wedged tube. Patients who underwent cryobiopsies using the tube-wedging method for diagnosing peripheral lung lesions from April 2018 to January 2019 were reviewed retrospectively. RESULTS: Twenty-four patients (diffuse lesions in 13 and localized lesions in 11) underwent cryobiopsies using the tube-wedging method during the study period. A median of three specimens (range; one to six specimens) were obtained by cryobiopsy. Cryobiopsy and forceps biopsy provided diagnostic material in 17 patients (71%) and 12 patients (50%), respectively. Median bronchoscopy time was 33.5 min (range; 16−56 min). Bleeding was controlled easily in all patients by bronchoscopic blood suctioning within the wedged tube, and there was no blood flooding out of the tube. CONCLUSIONS: The tube-wedging method is simple and safe, and may be a promising alternative to the balloon occlusion method for cryobiopsy. CLINICAL IMPLICATIONS: The tube-wedging method is a valuable option for safely performing a cryobiopsy. DISCLOSURES: No relevant relationships by Masahide Oki, source=Web Response No relevant relationships by HIDEO SAKA, source=Web Response

Does Moxa Smoke Have Significant Effect on the Acupuncturist's Respiratory System? A Population-Based Study.

Objectives To evaluate the safety of moxa smoke, especially to provide quantitative information and details for the occupational prevention of acupuncturists. Methods We combined the questionnaire-based cross-sectional survey and lung function testing-based historical retrospective cohort research to investigate the safety of moxa smoke exposure (MSE) among acupuncturists. A mathematical regression model was established to quantitatively evaluate the relationship between moxa smoke exposure and the respiratory health of the acupuncturist. The smoke exposure time of the acupuncturist and the prevalence of abnormal respiratory symptoms or diseases were also evaluated. Results (1) The cross-sectional research showed that the incidence of expectoration (18.7%) and rhinitis (22.7%) was the most common respiratory symptom and disease after MSE. No statistical difference was found between smoke exposure time of the acupuncturist and the prevalence of abnormal respiratory symptoms or diseases, except the prevalence of rhinitis and shortness of breath (P < 0.01). Regression model for the incidence of first three symptoms (expectoration, shortness of breath, and wheezing) from the cross-sectional survey indicated that the weight coefficients of factors associated with moxa smoke were lower than those of factors unrelated to moxa smoke, such as gender and personal history of respiratory diseases. (2) Historical retrospective cohort research showed that there was no significant difference in the % predicted PEF. No statistic difference was found between the exposed and nonexposed group in large airway function indexes (% predicted FEV1, % predicted FVC, and % predicted FEV1/FVC) and small airway function indexes (% predicted FEF25, % predicted FEF50, % predicted FEF75, and % predicted MMEF), either. Especially, the % predicted MVV among males (106.23 ± 2.92 vs. 95.56 ± 1.92, P < 0.01 and % predicted VC among females (100.70 ± 1.59 vs. 95.91 ± 1.61, P < 0.05) between the two groups had statistical significance, but did not cause pulmonary ventilation dysfunction. Conclusions MSE has no significant effect on the respiratory health of acupuncturists.

Driver Mutations in Normal Airway Epithelium Elucidate Spatiotemporal Resolution of Lung Cancer.

Rationale: Uninvolved normal-appearing airway epithelium has been shown to exhibit specific mutations characteristic of nearby non-small cell lung cancers (NSCLCs). Yet, its somatic mutational landscape in patients with early-stage NSCLC is unknown.Objectives: To comprehensively survey the somatic mutational architecture of the normal airway epithelium in patients with early-stage NSCLC.Methods: Multiregion normal airways, comprising tumor-adjacent small airways, tumor-distant large airways, nasal epithelium and uninvolved normal lung (collectively airway field), matched NSCLCs, and blood cells (n = 498) from 48 patients were interrogated for somatic single-nucleotide variants by deep-targeted DNA sequencing and for chromosomal allelic imbalance events by genome-wide genotype array profiling. Spatiotemporal relationships between the airway field and NSCLCs were assessed by phylogenetic analysis.Measurements and Main Results: Genomic airway field carcinogenesis was observed in 25 cases (52%). The airway field epithelium exhibited a total of 269 somatic mutations in most patients (n = 36) including key drivers that were shared with the NSCLCs. Allele frequencies of these acquired variants were overall higher in NSCLCs. Integrative analysis of single-nucleotide variants and allelic imbalance events revealed driver genes with shared "two-hit" alterations in the airway field (e.g., TP53, KRAS, KEAP1, STK11, and CDKN2A) and those with single hits progressing to two in the NSCLCs (e.g., PIK3CA and NOTCH1).Conclusions: Tumor-adjacent and tumor-distant normal-appearing airway epithelia exhibit somatic driver alterations that undergo selection-driven clonal expansion in NSCLC. These events offer spatiotemporal insights into the development of NSCLC and, thus, potential targets for early treatment.

AB009. Bioprosthetics in airway surgery

: Among many challenges in thoracic surgery, tracheal substitutes have been particularly elusive over nearly 75 years. Although nearly 4–5 cm of trachea can be resected and primarily reconstructed in properly selected patients, larger or more complicated resections have spawned innovation to overcome this limitation. The trachea functions as an airtight, mechanically stable passage from larynx to bronchi and facilitates clearance of secretions via a specialized epithelium. Ideal properties of a tracheal substitute include durable, non-immunogenic material that is resistant to infection and can easily incorporate surrounding tissue. Four methodologies have been implemented for airway reconstruction: autologous tissue, allotransplantation, bioprosthetics, and tissue engineering. Of note, complete circumferential prosthetic tracheal substitutes have historically failed. The most innovative solutions to tracheal replacement have been tissue engineering and bioprosthetics but both strategies have significant limitations. Tubularized aortic homograft supported by an endoluminal internal stent (Montgomery tube, silicone T-tube or nitinol stent) and external buttressing with muscle has been studied in patients with some limited success. A hypothesis has been put forward from some authors that aortic homografts contain undifferentiated stem cells that may play a role in migration, proliferation and cell signaling of host cells to form primitive tracheal elements including intima replacement with squamous or ciliated epithelium and chondrogenesis. In a few cases the internal stents were removed beyond 1–2 years with regeneration of cartilage elements within the graft. Despite this interesting biology, reported long-term complications include infection and tracheoesophageal fistula. Both aortic homograft and human acellular dermal matrix have experienced more success when implemented as a patch repair of large non-circumferential airway defects. The etiology of these defects can be derived from trauma with loss of tissue domain, infection and erosion (such as tracheoesophageal fistulae), or partial resection for neoplasm. In the case of human acellular dermal matrix the bioprosthetic is meticulously sutured so that the dermal side faces the airway lumen. Since this tissue matrix normally is broken down by the host, it primary serves as a scaffold for tissue ingrowth. Of note, the luminal side of aortic homograft is also oriented to face the airway lumen and the wall is perforated with a 16-gauge needle to promote tissue ingrowth and neovascularization. In the description of these reconstructions, repairs were routinely buttressed with vascularized tissue exteriorly and granulation tissue was observed at the site of reconstruction in many patients with mild tissue contracture and eventual native tissue ingrowth. It is understood that these patients require frequent surveillance bronchoscopy with debridement of granulation as necessary. Reported complications of this strategy were sputum retention, pneumonia and pneumomediastinum. One author reports selective use of hyperbaric oxygen in patients with complex repairs to enhance tissue ingrowth of the bioprosthetic. Tissue engineering generally involves the implantation of a biodegradable scaffold seeded with host cells that can repopulate the scaffold with new extracellular matrix. This has been reported in experimental settings with decellularized cadaveric trachea seeded with bone-marrow derived mesenchymal stroma cells as well as autologous respiratory epithelium. Initial attempts at tracheal tissue engineering showed promise in preclinical models but were associated with unacceptable outcomes in humans. Lastly, several studies have been published implementing three-dimensional (3D) printing technology to engineer tracheal substitutes that mimic mechanical behavior similar to native trachea. Biodegradable scaffolds of trachea have been 3D printed, some cultured with chondrocytes allowing formation of neocartilage, and tested in preclinical models. Although these investigations are very preliminary, 3D printing appears to provide infinite possibilities for tissue engineering.

Airway morphometry in COPD with bronchiectasis: a view on all airway generations.

The pathophysiological processes underlying bronchiectasis in chronic obstructive pulmonary disease (COPD) are not understood. In COPD, both small and large airways are progressively lost. It is currently not known to what extent the different airway generations of patients with COPD and bronchiectasis are involved.COPD explant lungs with bronchiectasis were compared to COPD explant lungs without bronchiectasis and unused donor lungs as controls. In order to investigate all airway generations, a multimodal imaging approach using different resolutions was conducted. Per group, five lungs were frozen (n=15) and underwent computed tomography (CT) imaging for large airway evaluation, with four tissue cores per lung imaged for measurements of the terminal bronchioles. Two additional lungs per group (n=6) were air-dried for lobar microCT images that allow airway segmentation and three-dimensional quantification of the complete airway tree.COPD lungs with bronchiectasis had significantly more airways compared to COPD lungs without bronchiectasis (p<0.001), with large airway numbers similar to control lungs. This difference was present in both upper and lower lobes. Lack of tapering was present (p=0.010) and larger diameters were demonstrated in lower lobes with bronchiectasis (p=0.010). MicroCT analysis of tissue cores showed similar reductions of tissue percentage, surface density and number of terminal bronchioles in both COPD groups compared to control lungs.Although terminal bronchioles were equally reduced in COPD lungs with and without bronchiectasis, significantly more large and small airways were found in COPD lungs with bronchiectasis.

The bridging bronchus: A comprehensive review of a rare, potentially life‐threatening congenital airway anomaly associated with cardiovascular defects

The bridging bronchus is a rare congenital airway anomaly in which the right upper lobe of the lung is supplied by the right main bronchus while the right lower lobe, and often the right middle lobe is supplied by an aberrant bronchus arising from the left main bronchus. The aberrant bronchus crosses (bridges) the lower part of the mediastinum, hence the term bridging bronchus (BB). This potentially life-threatening condition, usually accompanied by diffuse or focal airway stenosis, commonly presents with signs and symptoms related to large airway obstruction, such as respiratory distress, apnea, wheezing, stridor, and recurrent respiratory tract infections. Diagnosis of the BB is often challenging because the associated signs and symptoms mimic those of common conditions such as bacterial and viral bronchiolitis, bronchial asthma, cystic fibrosis, and foreign body aspiration. The BB is also often accompanied by congenital cardiovascular anomalies, including left pulmonary artery sling, atrial, and ventricular septal defects, tetralogy of Fallot, patent ductus arteriosus, and coarctation of the aorta. Patients presenting with the above signs and symptoms who are not responsive to standard treatment modalities, and have accompanying cardiovascular congenital anomalies should, therefore, be investigated for the BB. Herein, we review the anatomy, embryology, clinical presentation, differential diagnosis, imaging techniques and surgical management of the BB.

Feasibility study of using one-tenth mSv radiation dose in young children chest CT with 80 kVp and model-based iterative reconstruction

CT has become a routine imaging modality based on its excellent ability of displaying lung structures and diseases. But, how to reduce radiation dose of routine CT examination is a concern for radiologists. Our study aimed to evaluate the feasibility of using 80kVp and a model-based iterative reconstruction (MBIR) algorithm to achieve one-tenth mSv dose chest CT in infants and young children. Thirty-two cases (study group, average age 1.71 ± 1.01 years) underwent non-contrast chest CT examination at low dose with 80 kV, 4mAs and was reconstructed with MBIR (LD-MBIR) and the standard adaptive statistical iterative reconstruction (ASIR) algorithm (LD-ASIR); another group (control group) of 32 children underwent routine-dose chest CT with 100 kV and was reconstructed with ASIR only (RD-ASIR). The subjective and objective image quality of the three groups were measured and statistically compared. The radiation dose for the low dose scan was 0.09 ± 0.02 mSv, 6% of the routine dose. All LD-MBIR images were diagnostically acceptable. Compared with the RD-ASIR images, the LD-MBIR images were similar in noise in the left ventricle, muscles, lung field, on-par in displaying large airways, lung lucency and mediastinum, but were inferior in displaying lung marking, small airways and mediastinum. Thus, MBIR images with low dose in pediatric chest CT can be used in the diagnosis for lung field and air way disorders in infants and young children.

Characterization of an immortalized human small airway basal stem/progenitor cell line with airway region-specific differentiation capacity

BackgroundThe pathology of chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and most lung cancers involves the small airway epithelium (SAE), the single continuous layer of cells lining the airways ≥ 6th generations. The basal cells (BC) are the stem/progenitor cells of the SAE, responsible for the differentiation into intermediate cells and ciliated, club and mucous cells. To facilitate the study of the biology of the human SAE in health and disease, we immortalized and characterized a normal human SAE basal cell line.MethodsSmall airway basal cells were purified from brushed SAE of a healthy nonsmoker donor with a characteristic normal SAE transcriptome. The BC were immortalized by retrovirus-mediated telomerase reverse transcriptase (TERT) transduction and single cell drug selection. The resulting cell line (hSABCi-NS1.1) was characterized by RNAseq, TaqMan PCR, protein immunofluorescence, differentiation capacity on an air-liquid interface (ALI) culture, transepithelial electrical resistance (TEER), airway region-associated features and response to genetic modification with SPDEF.ResultsThe hSABCi-NS1.1 single-clone-derived cell line continued to proliferate for > 200 doubling levels and > 70 passages, continuing to maintain basal cell features (TP63+, KRT5+). When cultured on ALI, hSABCi-NS1.1 cells consistently formed tight junctions and differentiated into ciliated, club (SCGB1A1+), mucous (MUC5AC+, MUC5B+), neuroendocrine (CHGA+), ionocyte (FOXI1+) and surfactant protein positive cells (SFTPA+, SFTPB+, SFTPD+), observations confirmed by RNAseq and TaqMan PCR. Annotation enrichment analysis showed that “cilium” and “immunity” were enriched in functions of the top-1500 up-regulated genes. RNAseq reads alignment corroborated expression of CD4, CD74 and MHC-II. Compared to the large airway cell line BCi-NS1.1, differentiated of hSABCi-NS1.1 cells on ALI were enriched with small airway epithelial genes, including surfactant protein genes, LTF and small airway development relevant transcription factors NKX2–1, GATA6, SOX9, HOPX, ID2 and ETV5. Lentivirus-mediated expression of SPDEF in hSABCi-NS1.1 cells induced secretory cell metaplasia, accompanied with characteristic COPD-associated SAE secretory cell changes, including up-regulation of MSMB, CEACAM5 and down-regulation of LTF.ConclusionsThe immortalized hSABCi-NS1.1 cell line has diverse differentiation capacities and retains SAE features, which will be useful for understanding the biology of SAE, the pathogenesis of SAE-related diseases, and testing new pharmacologic agents.