Bronchoconstriction damages airway epithelia by crowding-induced excess cell extrusion.

Asthma is deemed an inflammatory disease, yet the defining diagnostic feature is mechanical bronchoconstriction. We previously discovered a conserved process called cell extrusion that drives homeostatic epithelial cell death when cells become too crowded. In this work, we show that the pathological crowding of a bronchoconstrictive attack causes so much epithelial cell extrusion that it damages the airways, resulting in inflammation and mucus secretion in both mice and humans. Although relaxing the airways with the rescue treatment albuterol did not affect these responses, inhibiting live cell extrusion signaling during bronchoconstriction prevented all these features. Our findings show that bronchoconstriction causes epithelial damage and inflammation by excess crowding-induced cell extrusion and suggest that blocking epithelial extrusion, instead of the ensuing downstream inflammation, could prevent the feed-forward asthma inflammatory cycle.

Artificial Intelligence-based CT Assessment of Bronchiectasis: The COPDGene Study.

Background CT is the standard method used to assess bronchiectasis. A higher airway-to-artery diameter ratio (AAR) is typically used to identify enlarged bronchi and bronchiectasis; however, current imaging methods are limited in assessing the extent of this metric in CT scans. Purpose To determine the extent of AARs using an artificial intelligence-based chest CT and assess the association of AARs with exacerbations over time. Materials and Methods In a secondary analysis of ever-smokers from the prospective, observational, multicenter COPDGene study, AARs were quantified using an artificial intelligence tool. The percentage of airways with AAR greater than 1 (a measure of airway dilatation) in each participant on chest CT scans was determined. Pulmonary exacerbations were prospectively determined through biannual follow-up (from July 2009 to September 2021). Multivariable zero-inflated regression models were used to assess the association between the percentage of airways with AAR greater than 1 and the total number of pulmonary exacerbations over follow-up. Covariates included demographics, lung function, and conventional CT parameters. Results Among 4192 participants (median age, 59 years; IQR, 52-67 years; 1878 men [45%]), 1834 had chronic obstructive pulmonary disease (COPD). During a 10-year follow-up and in adjusted models, the percentage of airways with AARs greater than 1 (quartile 4 vs 1) was associated with a higher total number of exacerbations (risk ratio [RR], 1.08; 95% CI: 1.02, 1.15; P = .01). In participants meeting clinical and imaging criteria of bronchiectasis (ie, clinical manifestations with ≥3% of AARs >1) versus those who did not, the RR was 1.37 (95% CI: 1.31, 1.43; P < .001). Among participants with COPD, the corresponding RRs were 1.10 (95% CI: 1.02, 1.18; P = .02) and 1.32 (95% CI: 1.26, 1.39; P < .001), respectively. Conclusion In ever-smokers with chronic obstructive pulmonary disease, artificial intelligence-based CT measures of bronchiectasis were associated with more exacerbations over time. Clinical trial registration no. NCT00608764 © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Schiebler and Seo in this issue.

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract.

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.

Exercise-induced Bronchodilation Equalizes Exercise Ventilatory Mechanics despite Variable Baseline Airway Function in Asthma.

PURPOSE: We quantified the magnitude of exercise-induced bronchodilation in adult asthmatics under conditions of narrowed and dilated airways. We then assessed the effect of the bronchodilation on ventilatory capacity and the extent of ventilatory limitation during exercise. METHODS: Eleven asthmatics completed three exercise bouts on a cycle ergometer. Exercise was preceded by no treatment (trialCON), inhaled ß2 agonist (trialBD), or a eucapnic voluntary hyperpnea challenge (trialBC). Maximal expiratory flow-volume maneuvers (MEFV) were performed before and within 40 s of exercise cessation. Exercise tidal flow-volume loops were placed within the preexercise and postexercise MEFV curve and used to determine expiratory flow limitation and maximum ventilatory capacity (V˙ECap). RESULTS: Preexercise airway function was different among the trials (forced expiratory volume 1 s during trialCON, trialBD, and trialBC = 3.3 ± 0.8 L, 3.8 ± 0.8 L, and 2.9 ± 0.8 L, respectively; P < 0.05). Maximal expired airflow increased with exercise during all three trials, but the increase was greatest during trialBC (delta forced expiratory volume 1 s during trialCON, trialBD, and trialBC = +12.2% ± 13.1%, +5.2% ± 5.7%, +28.1% ± 15.7%). Thus, the extent of expiratory flow limitation decreased, and V˙ECap increased, when the postexercise MEFV curve was used. During trialCON and trialBC, actual exercise ventilation exceeded V˙ECap calculated with the preexercise MEFV curve in seven and nine subjects, respectively. CONCLUSIONS: These findings demonstrate the critical importance of exercise bronchodilation in the asthmatic with narrowed airways. Of clinical relevance, the results also highlight the importance of assessing airway function during or immediately after exercise in asthmatic persons; otherwise, mechanical limitations to exercise ventilation will be overestimated.

C-EBPß mediates in cigarette/IL-17A-induced bronchial epithelial-mesenchymal transition in COPD mice.

BACKGROUND: Cigarettes smoking and IL-17A contribute to chronic obstructive pulmonary disease (COPD), and have synergistical effect on bronchial epithelial cell proliferation. CCAAT/enhancer-binding protein ß (C-EBPß) could be induced by IL-17A and is up-regulated in COPD. We explored the effect of cigarettes and IL-17 on bronchial epithelial-mesenchymal transition (EMT) in COPD mice and potential mechanism involved with C-EBPß in this study. METHODS: COPD model was established with mice by exposing to cigarettes. E-Cadherin, Vimentin, IL-17A and C-EBPß distributions were detected in lung tissues. Primary bronchial epithelial cells were separated from health mice and cocultured with cigarette smoke extract (CSE) or/and IL-17A. E-Cadherin, Vimentin and IL-17 receptor (IL-17R) expressions in vitro were assessed. When C-EBPß were silenced by siRNA in cells, E-Cadherin, Vimentin and C-EBPß expressions were detected. RESULTS: E-Cadherin distribution was less and Vimentin distribution was more in bronchus of COPD mice than controls. IL-17A and C-EBPß expressions were higher in lung tissues of COPD mice than controls. In vitro, C-EBPß protein expression was highest in CSE + IL-17A group, followed by CSE and IL-17A groups. E-cadherin expression in vitro was lowest and Vimentin expression was highest in CSE + IL-17A group, followed by CSE or IL-17A group. Those could be inhibited by C-EBPß silenced. CONCLUSIONS: C-EBPß mediates in cigarette/IL-17A-induced bronchial EMT in COPD mice. Our findings contribute to a better understanding on the progress from COPD to lung cancers, which will provide novel avenues in preventing tumorigenesis of airway in the context of cigarette smoking.

Effect of swirling flow and particle-release pattern on drug delivery to human tracheobronchial airways.

The present study aims to investigate the effect of swirling flow on particle deposition in a realistic human airway. A computational fluid dynamic (CFD) model was utilized for the simulation of oral inhalation and particle transport patterns, considering the k-ω turbulence model. Lagrangian particle tracking was used to track the particles' trajectories. A normal breathing condition (30 L/min) was applied, and two-micron particles were injected into the mouth, considering swirling flow to the oral inhalation airflow. Different cases were considered for releasing the particles, which evaluated the impacts of various parameters on the deposition efficiency (DE), including the swirl intensity, injection location and pattern of the particle. The work's novelty is applying several injection locations and diameters simultaneously. The results show that the swirling flow enhances the particle deposition efficiency (20-40%) versus no-swirl flow, especially in the mouth. However, releasing particles inside the mouth, or injecting them randomly with a smaller injection diameter (dinj) reduced DE in swirling flow condition, about 50 to 80%. Injecting particles inside the mouth can decrease DE by about 20%, and releasing particles with smaller dinj leads to 50% less DE in swirling flow. In conclusion, it is indicated that the airflow condition is an important parameter for a reliable drug delivery, and it is more beneficial to keep the inflow uniform and avoid swirling flow.

Bronchoscopic airway clearance therapy for acute exacerbations of bronchiectasis.

BACKGROUND: Persistent cough and large amounts of purulent sputum affects many bronchiectasis patients. No studies have evaluated the efficacy and safety of bronchoscopic airway clearance therapy and bronchoalveolar lavage (B-ACT) for non-cystic fibrosis bronchiectasis patients with acute exacerbation. METHODS: A randomised controlled trial was conducted to explore the efficacy and safety of B-ACT among 189 bronchiectasis inpatients from February 1, 2018 to February 28, 2019. The primary outcome was the time to first acute exacerbation. Secondary outcomes included changes of health-related scores, length of hospital stay, hospitalization expenses and incidences of adverse events. FINDINGS: B-ACT therapy significantly prolonged the median days to first acute exacerbation when compared with control group (198 vs 168 days, HR 0·555 (0·322-0·958), p=0·012; effect size(r)= 0·94). Further analysis showed that B-ACT therapy was more beneficial for these patients with severe disease and greater symptoms. COPD Assessment Test (CAT) scores improved significantly on the third day (5·45 vs 4·85, 0·60 (0·09-1·11), p=0·023), and Leicester Cough Questionnaire (LCQ) scores improved obviously on the third and seventh days (1·53 vs 1·23, 0·30 (0·05-0·55), p=0·044; 1·66 vs 1·32, 0·34 (0·08-0·60), p=0·022; respectively) after B-ACT therapy. Adverse events associated with B-ACT were mostly transient and mild. Differences of the lengths of hospital stay and hospitalization expenses in both group was not significant. INTERPRETATION: B-ACT therapy significantly prolonged the time to first acute exacerbation after discharge, highlighting the importance of B-ACT therapy focused on symptom improvements in preventing exacerbation. FUNDING: National Natural Science Foundation of China. TRIAL REGISTRY: ClinicalTrials.gov; No.:NCT03643302; URL: www.clinicaltrials.gov.

Thoracic Morphology and Bronchial Narrowing Are Related to Pulmonary Function in Adolescent Idiopathic Scoliosis.

BACKGROUND: In adolescent idiopathic scoliosis (AIS), lung function impairment is not necessarily related to the coronal spinal deformity. Recently, right-sided bronchial narrowing has been reported in thoracic AIS. The aim of this study was to describe the relation of chest and spinal deformity parameters, bronchial narrowing, and lung volumes with pulmonary function in preoperative AIS. METHODS: Spinal radiographs, low-dose computed tomographic (CT) scans of the spine including the chest, and pulmonary function tests were retrospectively collected for 85 preoperative patients with thoracic AIS in 2 centers and were compared with 14 matched controls. Three-dimensional lung and airway reconstructions were acquired. Correlation analysis was performed in which radiographic spinal parameters, CT-based thoracic deformity parameters (rib-hump index [RHi], spinal penetration index, endothoracic hump ratio, hemithoracic-width ratio), lung volume asymmetry, and bronchial cross-sectional area were compared with percent-of-predicted spirometry results. RESULTS: Forty-one patients (48%) had a percent-of-predicted forced expiratory volume in 1 second (FEV1%) or percent-of-predicted forced vital capacity (FVC%) of <65%, and 17 patients (20%) had obstructive lung disease. All thoracic deformity parameters correlated significantly with FEV1% and FVC%; RHi was found to be the best correlate (rs = -0.52 for FEV1% and -0.54 for FVC%). Patients with AIS with impaired pulmonary function had hypokyphosis, a larger rib hump, increased spinal and thoracic rotation, a narrower right hemithorax, and increased intrusion of the spine into the chest. Spinal intrusion correlated with right-sided bronchial narrowing, relative right lung volume loss, and decreased FEV1% and FVC%. Multivariate regression including spinal and thoracic deformity parameters, lung volume asymmetry, and airway parameters could explain 57% of the variance in FEV1% and 54% of the variance in FVC%. CONCLUSIONS: Chest intrusion by the endothoracic hump is related to right-sided bronchial narrowing and lung function loss in preoperative AIS. The findings support the theory that ventilatory dysfunction in thoracic AIS is not only restrictive but frequently has an obstructive component, especially in patients with hypokyphosis. RHi is the most predictive chest parameter for lung function loss. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Interactions via α2ß1 Cell Integrin May Protect against the Progression of Airway Structural Changes in Asthma.

Increased airway wall thickness and remodeling of bronchial mucosa are characteristic of asthma and may arise from altered integrin signaling on airway cells. Here, we analyzed the expression of ß1-subfamily integrins on blood and airway cells (flow cytometry), inflammatory biomarkers in serum and bronchoalveolar lavage, reticular basement membrane (RBM) thickness and collagen deposits in the mucosa (histology), and airway geometry (CT-imaging) in 92 asthma patients (persistent airflow limitation subtype: n = 47) and 36 controls. Persistent airflow limitation was associated with type-2 inflammation, elevated soluble α2 integrin chain, and changes in the bronchial wall geometry. Both subtypes of asthma showed thicker RBM than control, but collagen deposition and epithelial α1 and α2 integrins staining were similar. Type-I collagen accumulation and RBM thickness were inversely related to the epithelial expression of the α2 integrin chain. Expression of α2ß1 integrin on T-cells and eosinophils was not altered in asthma. Collagen I deposits were, however, more abundant in patients with lower α2ß1 integrin on blood and airway CD8+ T-cells. Thicker airway walls in CT were associated with lower α2 integrin chain on blood CD4+ T-cells and airway eosinophils. Our data suggest that α2ß1 integrin on inflammatory and epithelial cells may protect against airway remodeling advancement in asthma.

Airway diameter at different transpulmonary pressures in ex vivo sheep lungs: implications for deep inspiration-induced bronchodilation and bronchoprotection.

Deep inspiration (DI)-induced bronchodilation is the first line of defense against bronchoconstriction in healthy subjects. A hallmark of asthma is the lack of this beneficial effect of DI. The mechanism underlying the bronchodilatory effect of DI is not clear. Understanding the mechanism will help us unravel the mystery of asthma pathophysiology. It has been postulated that straining airway smooth muscle (ASM) during a DI could lead to bronchodilation and bronchoprotection. The hypothesis is currently under debate, and a central question is whether ASM is sufficiently stretched during a DI for its contractility to be compromised. Besides bronchoconstriction, another contributor to lung resistance is airway heterogeneity. The present study examines changes in airway diameter and heterogeneity at different lung volumes. Freshly explanted sheep lungs were used in plethysmographic measurements of lung resistance and elastance at different lung volumes, whereas the airway dimensions were measured by computed tomography (CT). The change in airway diameter informed by CT measurements was applied to isolated airway ring preparations to determine the strain-induced loss of ASM contractility. We found that changing the transpulmonary pressure from 5 to 30 cmH2O led to a 51% increase in lung volume, accompanied by a 46% increase in the airway diameter with no change in airway heterogeneity. When comparable airway strains measured in the whole lung were applied to isolated airway rings in either relaxed or contracted state, a significant loss of ASM contractility was observed, suggesting that DI-induced bronchodilation and bronchoprotection can result from strain-induced loss of ASM contractility.

Assessment of Extensive Airway Obstruction Using Point-by-Point Lateral Pressure Measurements during Bronchoscopy.

BACKGROUND: The positioning of the stent at the flow-limiting segment is crucial for patients with extensive airway obstruction to relieve dyspnea. However, CT and flow-volume curves cannot detect the area of maximal obstruction. OBJECTIVES: The aim of this study is to physiologically evaluate extensive airway obstruction during interventional bronchoscopy. METHODS: We prospectively measured point-by-point lateral airway pressure (Plat) at multiple points from the lower lobe bronchus to the upper trachea using a double-lumen catheter in 5 patients. The site of maximal obstruction was evaluated continuously to measure point-by-point Plat at multiple points when the airway catheter was withdrawn from the lower lobe bronchus to the upper trachea. RESULTS: Remarkable pressure differences occurred at the site of maximal obstruction assessed by point-by-point Plat measurements. After initial stenting in 1 case, migration of the maximal obstruction to a nonstented segment of the weakened airway was seen with extensive stenosis from the trachea to the bronchi. In the second case, in addition to radiological analysis, point-by-point Plat measurements could identify the location of the maximal obstruction which contributed to dyspnea. CONCLUSIONS: Point-by-point Plat measurement could be used to detect the site of maximal obstruction physiologically. Furthermore, Plat measurement could assess the need for additional procedures in real time in patients with extensive airway obstruction.

Reduction of bronchial response to mannitol after partial switch from conventional tobacco to electronic cigarette consumption.

BACKGROUND: Regarding the multiple health effects of e-cigarettes, there are insufficient data on potential effects on bronchial reactivity (BHR). In the present study, we assessed the impact of a switch from conventional to e-cigarettes on BHR under realistic conditions over a period of 3 months. METHODS: Sixty subjects who declared to reduce or stop their tobacco consumption by inhalation of nicotine-containing liquids via e-cigarette, and 20 volunteers participating in a stop-smoking program were included. Data was analysed using parametric and non-parametric statistical procedures. Spirometry, determinations of exhaled carbon monoxide (eCO) and nitric oxide (FeNO), provocation testing with mannitol as an indirect bronchial stimulus, and cotinine measurements were used to investigate BHR and nicotine abstinence. RESULTS: BHR to mannitol significantly decreased in the group using e-cigarettes and nicotine-containing liquids over a period of three months in this real-life setting. Participants reduced their tobacco consumption to about 25% or lower, confirmed by a reduction in eCO. Changes in lung function and FeNO were small and not statistically significant, and changes in the stop-smoking group were similar to those in the e-cigarette group. CONCLUSION: The reduction in BHR that can be expected after a reduction of cigarette consumption was not abolished by the concomitant use of e-cigarettes. Whether the decrease in BHR observed after 3 months is maintained when using e-cigarettes over longer time periods or has an individual prognostic value, must be clarified in long-term studies.

Prediction of risk factors of bronchial mucus plugs in children with Mycoplasma pneumoniae pneumonia.

BACKGROUND: Recently, many cases of pneumonia in children with Mycoplasma pneumoniae infection have been shown to have varying degrees of intrabronchial mucus plug formation. The clinical, laboratory, radiological characteristics, and treatment of patients with Mycoplasma infection are analyzed in this study. The risk factors for M. pneumoniae pneumonia (MPP) mucus plug formation in children are explored, and a risk factor scoring system is established. METHODS: MPP patients treated with bronchoscopy were retrospectively enrolled in the study from February 2015 to December 2019. The children were divided into a mucus plug group and a control group according to the presence or absence of mucus plug formation. The clinical, laboratory, radiological characteristics, and treatment of the two groups of children were compared. Univariate and multivariate logistic regression models were used to identify the risk factors for MPP mucus plug formation. The receiver operating characteristic (ROC) curve was drawn to evaluate the regression model and establish the MPP mucous plug risk factor scoring system. RESULTS: A univariate analysis showed that the children in the mucous group were older and had a longer fever duration, longer hospital stay, higher fever peak, more cases of wheezing symptoms and allergies, and azithromycin or corticosteroids were administered later. In addition, neutrophil, C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer (DD), sputum MP-DNA copy number, and total immunoglobulin A (IgA) levels were higher, while prealbumin (PA) levels were lower. The ROC curve analysis showed that children with MPP had PA ≤144.5 mg/L, had used corticosteroids during the course of the illness of ≥4.5 days, CRP ≥12.27 mg/L, an LDH ≥ 462.65 U/L, and there was a possibility of intra-airway mucus formation. The independent risk factors were scored according to their odds ratio (OR) value. Among the 255 children with MPP, the high-risk group had 44 (83.02%) mucus plugs out of 53; the middle-risk group had 35 (34.3%) mucus plugs out of 102; and the low-risk group had 11 (11%) mucus plugs out of 100. CONCLUSIONS: PA levels, timing of corticosteroid use (use in the first few days), CRP levels, and LDH levels were independent risk factors for MPP mucus plug formation. This provides a basis for the early identification of MPP in children combined with mucus plug formation.

Pitfalls in Expiratory Flow Limitation Assessment at Peak Exercise in Children: Role of Thoracic Gas Compression.

PURPOSE: Thoracic gas compression and exercise-induced bronchodilation can influence the assessment of expiratory flow limitation (EFL) during cardiopulmonary exercise tests. The purpose of this study was to examine the effect of thoracic gas compression and exercise-induced bronchodilation on the assessment of EFL in children with and without obesity. METHODS: Forty children (10.7 ± 1.0 yr; 27 obese; 15 with EFL) completed pulmonary function tests and incremental exercise tests. Inspiratory capacity maneuvers were performed during the incremental exercise test for the placement of tidal flow volume loops within the maximal expiratory flow volume (MEFV) loops, and EFL was calculated as the overlap between the tidal and the MEFV loops. MEFV loops were plotted with volume measured at the lung using plethysmography (MEFVp), with volume measured at the mouth using spirometry concurrent with measurements in the plethysmograph (MEFVm), and from spirometry before (MEFVpre) and after (MEFVpost) the incremental exercise test. Only the MEFVp loops were corrected for thoracic gas compression. RESULTS: Not correcting for thoracic gas compression resulted in incorrect diagnosis of EFL in 23% of children at peak exercise. EFL was 26% ± 15% VT higher for MEFVm compared with MEFVp (P < 0.001), with no differences between children with and without obesity (P = 0.833). The difference in EFL estimation using MEFVpre (37% ± 30% VT) and MEFVpost (31% ± 26% VT) did not reach statistical significance (P = 0.346). CONCLUSIONS: Not correcting the MEFV loops for thoracic gas compression leads to the overdiagnosis and overestimation of EFL. Because most commercially available metabolic measurement systems do not correct for thoracic gas compression during spirometry, there may be a significant overdiagnosis of EFL in cardiopulmonary exercise testing. Therefore, clinicians must exercise caution while interpreting EFL when the MEFV loop is derived through spirometry.

Rheological analysis of sputum from patients with chronic bronchial diseases.

Bronchial diseases are characterised by the weak efficiency of mucus transport through the lower airways, leading in some cases to the muco-obstruction of bronchi. It has been hypothesised that this loss of clearance results from alterations in the mucus rheology, which are reflected in sputum samples collected from patients, making sputum rheology a possible biophysical marker of these diseases and their evolution. However, previous rheological studies have focused on quasi-static viscoelastic (linear storage and loss moduli) properties only, which are not representative of the mucus mobilisation within the respiratory tract. In this paper, we extend this approach further, by analysing both quasi-static and some dynamic (flow point) properties, to assess their usability and relative performance in characterising several chronic bronchial diseases (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) and distinguishing them from healthy subjects. We demonstrate that pathologies influence substantially the linear and flow properties. Linear moduli are weakly condition-specific and even though the corresponding ranges overlap, distinct levels can be identified. This directly relates to the specific mucus structure in each case. In contrast, the flow point is found to strongly increase in muco-obstructive diseases, which may reflect the complete failure of mucociliary clearance causing episodic obstructions. These results suggest that the analysis of quasi-static and dynamic regimes in sputum rheology is in fact useful as these regimes provide complementary markers of chronic bronchial diseases.

Thoracic Computed Tomography Scan and Bronchoscopy Appearance of Mounier-Kuhn Syndrome: A Case Report.

Mounier-Kuhn syndrome (MKS) is a rare congenital disease with an autosomal recessive inheritance pattern, characterized by an enlargement of the trachea and bronchi. MKS is secondary to a thinning of the muscular mucosa and atrophy of the longitudinal muscle and elastic fibers of the tracheobronchial tree. As a consequence, tracheal diverticulosis and dilatations in the posterior membranous wall appear, along with bronchiectasis that tend to be cystic in appearance. Overall, there is an impairment of mucocilliary clearance, with an ineffective cough, which predisposes the patient to recurrent lower respiratory tract infections. Clinical manifestations vary from asymptomatic to respiratory failure and death, most patients being diagnosed between the third and fourth decades of life. It is an often undiagnosed disease, with a diagnostic algorithm that includes the use of radiological techniques, alone or in combination with bronchoscopy. Specific diagnostic criteria have been developed, based on patients' tracheal and main bronchi diameter on chest X-ray and thoracic computed tomography scan. We present the case of a 45-year-old African American man who presented with a history of multiples episodes of pneumonia that required management in the intensive care unit, on whom MKS was diagnosed.

ADAM15 expression is increased in lung CD8+ T cells, macrophages, and bronchial epithelial cells in patients with COPD and is inversely related to airflow obstruction.

BACKGROUND: A disintegrin and metalloproteinase domain-15 (ADAM15) is expressed by activated leukocytes, and fibroblasts in vitro. Whether ADAM15 expression is increased in the lungs of COPD patients is not known. METHODS: ADAM15 gene expression and/or protein levels were measured in whole lung and bronchoalveolar lavage (BAL) macrophage samples obtained from COPD patients, smokers, and non-smokers. Soluble ADAM15 protein levels were measured in BAL fluid (BALF) and plasma samples from COPD patients and controls. Cells expressing ADAM15 in the lungs were identified using immunostaining. Staining for ADAM15 in different cells in the lungs was related to forced expiratory volume in 1 s (FEV1), ratio of FEV1 to forced vital capacity (FEV1/FVC), and pack-years of smoking history. RESULTS: ADAM15 gene expression and/or protein levels were increased in alveolar macrophages and whole lung samples from COPD patients versus smokers and non-smokers. Soluble ADAM15 protein levels were similar in BALF and plasma samples from COPD patients and controls. ADAM15 immunostaining was increased in macrophages, CD8+ T cells, epithelial cells, and airway α-smooth muscle (α-SMA)-positive cells in the lungs of COPD patients. ADAM15 immunostaining in macrophages, CD8+ T cells and bronchial (but not alveolar) epithelial cells was related inversely to FEV1 and FEV1/FVC, but not to pack-years of smoking history. ADAM15 staining levels in airway α-SMA-positive cells was directly related to FEV1/FVC. Over-expressing ADAM15 in THP-1 cells reduced their release of matrix metalloproteinases and CCL2. CONCLUSIONS: These results link increased ADAM15 expression especially in lung leukocytes and bronchial epithelial cells to the pathogenesis of COPD.

Anesthetic Approach to Postpneumonectomy Syndrome.

Postpneumonectomy syndrome is a rare complication in patients who have previously had a pneumonectomy. Over time, the mediastinum may rotate toward the vacant pleural space, which can cause extrinsic airway and esophageal compression. As such, these patients typically present with progressive dyspnea and dysphagia. There is a paucity of reports in the anesthesiology literature regarding the intraoperative anesthetic approach to such rare patients. We present a case of an 18-year-old female found to have postpneumonectomy syndrome requiring thoracotomy with insertion of tissue expanders. Our case report illustrates the complexities involved in the care of these patients with regards to airway management, ventilation concerns, and potential for hemodynamic compromise. This case report underscores the importance of extensive multidisciplinary planning.