Nematode ascarosides attenuate mammalian type 2 inflammatory responses.

Mounting evidence suggests that nematode infection can protect against disorders of immune dysregulation. Administration of live parasites or their excretory/secretory (ES) products has shown therapeutic effects across a wide range of animal models for immune disorders, including asthma. Human clinical trials of live parasite ingestion for the treatment of immune disorders have produced promising results, yet concerns persist regarding the ingestion of pathogenic organisms and the immunogenicity of protein components. Despite extensive efforts to define the active components of ES products, no small molecules with immune regulatory activity have been identified from nematodes. Here we show that an evolutionarily conserved family of nematode pheromones called ascarosides strongly modulates the pulmonary immune response and reduces asthma severity in mice. Screening the inhibitory effects of ascarosides produced by animal-parasitic nematodes on the development of asthma in an ovalbumin (OVA) murine model, we found that administration of nanogram quantities of ascr#7 prevented the development of lung eosinophilia, goblet cell metaplasia, and airway hyperreactivity. Ascr#7 suppressed the production of IL-33 from lung epithelial cells and reduced the number of memory-type pathogenic Th2 cells and ILC2s in the lung, both key drivers of the pathology of asthma. Our findings suggest that the mammalian immune system recognizes ascarosides as an evolutionarily conserved molecular signature of parasitic nematodes. The identification of a nematode-produced small molecule underlying the well-documented immunomodulatory effects of ES products may enable the development of treatment strategies for allergic diseases.

Expiratory central airway collapse during positive pressure ventilation: a case report.

BACKGROUND: Physiologic narrowing of the central airway occurs during expiration. Conditions in which this narrowing becomes excessive are referred to as expiratory central airway collapse. Expiratory central airway collapse is usually managed by applying positive pressure to the airways, which acts as a pneumatic stent. The particularity of the case reported here included the patient's left main bronchus being permeable during spontaneous breathing but collapsing during general anaesthesia, despite positive pressure ventilation and positive end-expiratory pressure. CASE PRESENTATION: We present the case of a 55-year-old man admitted for the placement of a ureteral JJ stent. Rapid desaturation occurred a few minutes after the onset of anaesthesia. After excluding the most common causes of desaturation, fibreoptic bronchoscopy was performed through the tracheal tube and revealed complete collapse of the left main bronchus. The collapse persisted despite the application of positive end-expiratory pressure and several recruitment manoeuvres. After recovery of spontaneous ventilation, the collapse was lifted, and saturation increased back to normal levels. No evidence of extrinsic compression was found on chest X-rays or computed tomography scans. CONCLUSION: Cases of unknown expiratory central airway collapse reported in the literature were usually managed with positive pressure ventilation. This approach has been unsuccessful in the case described herein. Our hypothesis is that mechanical bending of the left main bronchus occurred due to loss of the patient's natural position and thoracic muscle tone under general anaesthesia with neuromuscular blockade. When possible, spontaneous ventilation should be maintained in patients with known or suspected ECAC.

The preventive and therapeutic effects of AAV1-KLF4-shRNA in cigarette smoke-induced pulmonary hypertension.

We found previously that KLF4 expression was up-regulated in cultured rat and human pulmonary artery smooth muscle cells (PASMCs) exposed to cigarette smoke (CS) extract and in pulmonary artery from rats with pulmonary hypertension induced by CS. Here, we aim to investigate whether CS-induced pulmonary hypertension (PH) is prevented and ameliorated by targeted pulmonary vascular gene knockdown of KLF4 via adeno-associated virus 1 (AAV1)-KLF4-shRNA in vivo in rat model. The preventive and therapeutic effects were observed according to the different time-point of AAV1-KLF4-shRNA intratracheal administration. We tested haemodynamic measurements of systemic and pulmonary circulations and observed the degree of pulmonary vascular remodelling. In the preventive experiment, KLF4 expression and some pulmonary circulation hemodynamic measurements such as right ventricular systolic pressure (RVSP), mean right ventricular pressure (mRVP), peak RV pressure rate of rise (dP/dt max) and right ventricle (RV) contractility index were increased significantly in the CS-induced PH model. While in the prevention group (AAV1-KLF4-shRNA group), RVSP, mRVP, dP/dt max and RV contractility index which are associated with systolic function of right ventricle decreased and the degree of pulmonary vascular remodelling relieved. In the therapeutic experiment, we observed a similar trend. Our findings emphasize the feasibility of sustained pulmonary vascular KLF4 gene knockdown using intratracheal delivery of AAV1 in an animal model of cigarette smoke-induced PH and determined gene transfer of KLF4-shRNA could prevent and ameliorate the progression of PH.

Computational Fluid Dynamic Modeling Reveals Nonlinear Airway Stress during Trachea Development.

Normative trachea dimensions and aerodynamic information during development was collected to establish clinical benchmarks and showed that airway development seems to outpace respiratory demands. Infants and toddlers' trachea exhibit higher aerodynamic stress that significantly decreases by teenage years. This implies large airway pathology in younger children may have a more substantial clinical impact.

Common pathogenesis for sirenomelia, OEIS complex, limb-body wall defect, and other malformations of caudal structures.

Decades of clinical, pathological, and epidemiological study and the recent application of advanced microarray and gene sequencing technologies have led to an understanding of the causes and pathogenesis of most recognized patterns of malformation. Still, there remain a number of patterns of malformation whose pathogenesis has not been established. Six such patterns of malformation are sirenomelia, VACTERL association, OEIS complex, limb-body wall defect (LBWD), urorectal septum malformation (URSM) sequence, and MURCS association, all of which predominantly affect caudal structures. On the basis of the overlap of the component malformations, the co-occurrence in individual fetuses, and the findings on fetal examination, a common pathogenesis is proposed for these patterns of malformation. The presence of a single artery in the umbilical cord provides a visible clue to the pathogenesis of all cases of sirenomelia and 30%-50% of cases of VACTERL association, OEIS complex, URSM sequence, and LBWD. The single artery is formed by a coalescence of arteries that supply the yolk sac, arises from the descending aorta high in the abdominal cavity, and redirects blood flow from the developing caudal structures of the embryo to the placenta. This phenomenon during embryogenesis is termed vitelline vascular steal.

CPAP protects against hyperoxia-induced increase in airway reactivity in neonatal mice.

BACKGROUND: Oxygen and continuous positive airway pressure (CPAP) are primary modes of respiratory support for preterm infants. Animal models, however, have demonstrated adverse unintended effects of hyperoxia and CPAP on lung development. We investigate the effects of combined neonatal hyperoxia and CPAP exposure on airway function and morphology in mice. METHODS: Newborn mice were exposed to hyperoxia (40% O2) 24 h/day for 7 consecutive days with or without daily (3 h/day) concomitant CPAP. Two weeks after CPAP and/or hyperoxia treatment ended, lungs were assessed for airway (AW) hyperreactivity and morphology. RESULTS: CPAP and hyperoxia exposure alone increased airway reactivity compared to untreated control mice. CPAP-induced airway hyperreactivity was associated with epithelial and smooth muscle proliferation. In contrast, combined CPAP and hyperoxia treatment no longer resulted in increased airway reactivity, which was associated with normalization of smooth muscle and epithelial proliferation to values similar to untreated mice. CONCLUSIONS: Our data suggest that the combination of CPAP and hyperoxia decreases the adverse consequences on airway remodeling of either intervention alone. The complex interaction between mechanical stretch (via CPAP) and hyperoxia exposure on development of immature airways has implications for the pathophysiology of airway disease in former preterm infants receiving non-invasive respiratory support. IMPACT: CPAP and mild hyperoxia exposure alone increase airway reactivity in the neonatal mouse model. In contrast, combined CPAP and hyperoxia no longer induce airway hyperreactivity. Combined CPAP and hyperoxia normalize smooth muscle and epithelial proliferation to control values. Interaction between CPAP-induced stretch and mild hyperoxia exposure on immature airways has important implications for airway pathophysiology in former preterm infants.

Effects of upper airway obstruction or hypoxia on gastroesophageal reflux in newborn lambs.

BACKGROUND: Although it is commonly accepted that upper airway obstruction (UAO) increases gastroesophageal reflux (GER), the link is poorly understood and insufficiently documented. In addition, while hypoxia is often encountered in infants with UAO, its consequences on GER are virtually unknown. The two aims of the present study were to characterize the effects of (1) UAO and (2) hypoxia on GER. METHODS: Seventeen lambs underwent polysomnographic and esophageal impedance/pH-metry monitoring during UAO vs. a control condition (6 h, ten lambs) or 10% hypoxia vs. normoxic condition (3 h, seven other lambs). RESULTS: Moderate-to-severe UAO was maintained throughout monitoring (inspiratory tracheal pressure of -13 (-15, -12) cm H2O vs. -1 (-1, -1) cm H2O in control condition, p = 0.005). While the number of GERs increased with UAO (2 (1, 4) vs. 0 (0, 3) in the control condition, p = 0.03), the increase was less than anticipated and inconsistent among the lambs. Also, sustained 10% hypoxia did not alter the number of GERs (2 (1, 3) vs. 0 (0, 5) in the control condition, p = 0.9). CONCLUSIONS: The presence of an UAO for 6 h mildly increased the number of GERs, whereas hypoxia for 3 h had no significant effect. IMPACT: The effect of upper airway obstruction and hypoxia on gastroesophageal reflux is poorly documented in the neonatal period. A moderate-to-severe upper airway obstruction for 6 h results in a mild, inconsistent increase in the number of gastroesophageal refluxes. Overall, a hypoxia of 10% for 3 h had no significant impact on gastroesophageal reflux. The prescription of an antireflux medication in infants with upper airway obstruction must not be systematic but rely on objective signs of a pathologic gastroesophageal reflux.

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.

Human airway branch variation and chronic obstructive pulmonary disease.

Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts (n = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung. The second most common airway branch variant is associated with COPD among smokers, with narrower airway lumens in all lobes, and with genetic polymorphisms within the FGF10 gene. We conclude that central airway branch variation, readily detected by computed tomography, is a biomarker of widely altered lung structure with a genetic basis and represents a COPD susceptibility factor.

Tracheomegaly among Extremely Preterm Infants on Prolonged Mechanical Ventilation.

By using phantom radiographs, the accuracy of tracheal measurements was established. Preterm infants (≤29 weeks) were enrolled in short (<7 days) and prolonged ventilation (≥28 days) groups. Both groups had 3 weight categories, namely, <1000 g, 1000-1999 g, and >2000 g. Tracheal sizes were measured on serial chest radiographs (CXR). We noted tracheomegaly in association with prolonged ventilation at ≥1000 g.

Genetic diagnoses and associated anomalies in fetuses prenatally diagnosed with esophageal atresia.

Esophageal atresia (EA) is a congenital anomaly occurring in 2.3 per 10,000 live births. Due to advances in prenatal imaging, EA is more readily diagnosed, but data on the associated genetic diagnoses, other anomalies, and postnatal outcome for fetuses diagnosed prenatally with EA are scarce. We collected data from two academic medical centers (n = 61). Our data included fetuses with suspected EA on prenatal imaging that was confirmed postnatally and had at least one genetic test. In our cohort of 61 cases, 29 (49%) were born prematurely and 19% of those born alive died in the first 9 years of life. The most commonly associated birth defects were cardiac anomalies (67%) and spine anomalies (50%). A diagnosis was made in 61% of the cases; the most common diagnoses were vertebral defects, anal atresia, cardiac anomalies, tracheoesophageal fistula with esophageal atresia, radial or renal dysplasia, and limb anomalies association (43%, although 12% met only 2 of the criteria), trisomy 21 (5%), and CHARGE syndrome (5%). Our findings suggest that most fetuses with prenatally diagnosed EA have one or more additional major anomaly that warrants a more comprehensive clinical genetics evaluation. Fetuses diagnosed prenatally appear to represent a cohort with a worse outcome.

Analysis of wheeze sounds during tidal breathing according to severity levels in asthma patients.

Objective: This study aimed to statistically analyze the behavior of time-frequency features in digital recordings of wheeze sounds obtained from patients with various levels of asthma severity (mild, moderate, and severe), and this analysis was based on the auscultation location and/or breath phase. Method: Segmented and validated wheeze sounds were collected from the trachea and lower lung base (LLB) of 55 asthmatic patients during tidal breathing maneuvers and grouped into nine different datasets. The quartile frequencies F25, F50, F75, F90 and F99, mean frequency (MF) and average power (AP) were computed as features, and a univariate statistical analysis was then performed to analyze the behavior of the time-frequency features. Results: All features generally showed statistical significance in most of the datasets for all severity levels [χ2 = 6.021-71.65, p < 0.05, η2 = 0.01-0.52]. Of the seven investigated features, only AP showed statistical significance in all the datasets. F25, F75, F90 and F99 exhibited statistical significance in at least six datasets [χ2 = 4.852-65.63, p < 0.05, η2 = 0.01-0.52], and F25, F50 and MF showed statistical significance with a large η2 in all trachea-related datasets [χ2 = 13.54-55.32, p < 0.05, η2 = 0.13-0.33]. Conclusion: The results obtained for the time-frequency features revealed that (1) the asthma severity levels of patients can be identified through a set of selected features with tidal breathing, (2) tracheal wheeze sounds are more sensitive and specific predictors of severity levels and (3) inspiratory and expiratory wheeze sounds are almost equally informative.

Leptin induces a contracting effect on guinea pig tracheal smooth muscle via the Ob-R receptor mechanism: novel evidence.

The purpose of this study was to explore the potential contracting effect of leptin on isolated guinea pig tracheal smooth muscle (TSM), the possible mechanism, and the impact of epithelium denudation or allergen sensitization, respectively. An in vitro experiment investigated the effect of leptin at a concentration of 250-1000 nmol/L on isolated guinea pig TSM with an intact or denuded epithelium. Ovalbumin and IgE were used to test the impact of active and passive sensitization. The isolated TSM strips were incubated in Krebs solution and aerated with carbogen (95% O2 and 5% CO2) via an automated tissue organ bath system (n = 4 for each group). Isometric contractions were recorded digitally using iox2 data acquisition software. The possible mechanism of leptin-induced TSM contraction was examined by preincubation with leptin receptor (Ob-R) antagonist. Leptin had significant concentration-dependent contraction effects on guinea pig TSM (p < 0.05). Epithelium denuding and active or passive sensitization significantly increased the potency of the leptin. Preincubation with a leptin receptor (Ob-R) antagonist significantly reduced the contraction effects, suggesting an Ob-R-mediated mechanism. Leptin had a contracting effect on airway smooth muscles potentiated by either epithelium denuding or sensitization, and the Ob-R mechanism was a possible effect mediator.

Respiratory-Swallow Pattern Following Total Laryngectomy.

The goal of this study was to further characterize respiratory patterns in total laryngectomees with attention to respiratory-swallow pattern as it relates to presence/absence of tracheoesophageal puncture (TEP) and bolus consistency. It was hypothesized that participants with TEP would exhibit respiratory-swallow patterns that were significantly different than those without TEP and that bolus consistency (thin or solid) would modulate respiratory-swallow pattern. Data were collected from 12 adults (8 male), aged 46-67 years (mean 57) status post total laryngectomy (1-30 years; average 6 years). Those actively receiving chemoradiation, with history of esophageal cancer, with neurologic disease, with history of lung cancer, with known or suspected recurrence of head and neck cancer (HNC), or with severe cognitive deficits were excluded. Laryngectomy participants were asked to swallow three sips of water and three bites of graham cracker. Submental surface EMG activity was used to detect swallows and a custom stoma mask in line with a pneumotachograph measured airflow during the swallows. Non-parametric Mann-Whitney test for differences was used to detect significance for our dependent variables, TEP or bolus consistency and independent variables, respiratory-swallow pattern. Laryngectomee's showed preference for swallow during inspiration which is inconsistent with the expiratory pattern preference found in healthy adults with intact larynges by McFarland et al. (Respir Physiol Neurobiol 234:89-96, 2016) but consistent with the pattern preference for inspiration (or non-dominant respiratory-swallow phase pattern) found in the HNC population at-large by Brodsky et al. (J Appl Physiol 112(10):1698-1705, 2012). No significant difference was found in swallow pattern with regards to presence/absence of TEP or bolus consistency.

Objective Assessment of Postoperative Swallowing Difficulty Through Ultrasound in Patients Undergoing Thyroidectomy.

Swallowing discomfort is a common postoperative complaint in patients undergoing thyroidectomy. Contraction of the strap muscles might cause resistance to elevation of the laryngotracheal unit, and downward movement of the laryngotracheal unit may lead to swallowing discomfort. However, few studies have evaluated the mechanism related to limited laryngotracheal elevation after thyroidectomy. We aimed to objectively verify the presence of postoperative impaired laryngotracheal elevation through ultrasound evaluation in patients undergoing thyroidectomy and evaluate its relationship with limitation of laryngotracheal elevation. This is a prospective clinical study. Among patients undergoing hemithyroidectomy and total thyroidectomy, the patients who were followed up for ≥ 6 months were selected (N = 40). Ultrasound evaluation was done preoperatively and at 1, 3, and 6 months postoperatively. Laryngotracheal movement was recorded and the length of elevation was measured. Symptom after thyroidectomy was evaluated through swallowing-related items of thyroidectomy-related voice questionnaire. Ultrasound evaluation verified the presence of limited laryngotracheal elevation postoperatively in patients undergoing thyroidectomy. After thyroidectomy, the swallowing-related score was significantly increased, and was recovered time-dependently at 1 month. Laryngotracheal elevation showed significant decrease after thyroidectomy. The symptom score of swallowing was significantly correlated with the length of laryngotracheal elevation. Post-thyroidectomy ultrasound evaluation verified that laryngotracheal elevation was significantly impaired. Presence of adhesion between the laryngotracheal unit and the superficial soft tissue was the probable cause of the limitation at 6 months after thyroidectomy. The length of laryngotracheal elevation was related to the symptom score of swallowing after thyroid surgery.

Detection of intratracheal accumulation of thick secretions by using continuous monitoring of respiratory acoustic spectrum: a preliminary analysis.

The accumulation of tracheobronchial secretions may contribute to a deterioration in pulmonary function and its early detection is important. In this study, we analyzed the respiratory sound spectrum in patients with intratracheal secretion, and compared acoustic characteristics before and after therapeutic endotracheal suctioning. After review of anesthetic records of liver transplant recipients, we included recipients with identified intratracheal secretion during surgery. Intraoperative breath sounds recorded through esophageal stethoscope were sampled in 20 s-period before and after suctioning of secretion and analyzed using fast Fourier transform. We also analyzed normal breath sounds from recipients without any respiratory problem as control group. The maximal power (dBmMax), total power from whole frequency range of 80-500 Hz (Pt), total power of each frequency range (80-200 Hz, P80-200; 200-300 Hz, P200-300; 300-400 Hz, P300-400; 400-500 Hz, P400-500), and their ratio (P80-200/Pt, P200-300/Pt, P300-400/Pt, P400-500/Pt) were compared. Breath sounds were obtained from 20 recipients; 9 pairs of breath sound before and after suctioning of secretion and 11 normal breath sounds. Patients with intratracheal secretion showed significantly higher P80-200, P200-300, P300-400, P400-500 when compared to the those of normal control patients (P = 0.003, P = 0.002, and P = 0.009, respectively), while dBmMax did not differ. Elimination of secretions attenuated P80-200, P200-300, P300-400, and P400-500 by 22.4%, 25.7%, 48.5%, and 15.3%, respectively (P = 0.002, 0.024, 0.009, and 0.016, respectively). Identifying the presence of intratracheal secretions with power ratio at 80-200 Hz and 300-400 Hz showed the highest area under the curve of 0.955 in receiver operating characteristic curve analysis. We suggest that spectral analysis of breath sounds obtained from the esophageal stethoscope might be a useful non-invasive respiratory monitor for accumulation of intratracheal secretion. Further prospective studies to evaluate the utility of acoustic analysis in surgical patients are warranted.

Calcium and potassium channels are involved in curcumin relaxant effect on tracheal smooth muscles.

Context: Curcumin, the active component of Curcuma longa L. (Zingiberaceae), exhibits a wide variety of biological activities including vasodilation and anti-inflammation.Objective: The relaxant effect of curcumin in tracheal smooth muscle (TSM) was not examined so far, thus, this study was designed to assess the relaxant effect of curcumin on rat TSM and examine the underlying mechanism(s) responsible for this effect.Materials and methods: TSM was contracted by KCl (60 mM) or methacholine (10 µM), and cumulative concentrations of curcumin (12.5, 25, 50, and 100 mg/mL) or theophylline (0.2, 0.4, 0.6, and 0.8 mM, as positive control) were added to organ bath. The relaxant effect of curcumin was examined in non-incubated or incubated tissues with atropine (1 µM), chlorpheniramine (1 µM), indomethacin (1 µM), and papaverine (100 µM).Results: In non-incubated TSM, curcumin showed significant relaxant effects on KCl-induced contraction in a concentration-dependent manner (p < 0.001 for all concentrations). The relaxant effects of curcumin 12.5, 25, and 50 mg/mL were significantly lower in atropine-incubated tissue compared to non-incubated TSM (p < 0.05 to p < 0.001). A significant difference was observed in EC50 between atropine-incubated (48.10 ± 2.55) and non-incubated (41.65 ± 1.81) tissues (p < 0.05). Theophylline showed a significant relaxant effect on both KCl and methacholine-induced contraction in a concentration-dependent manner (p < 0.001 for all cases).Conclusions: The results indicated a relatively potent relaxant effect of curcumin on TSM, which was less marked than the effect of theophylline. Calcium channel blocking and/or potassium channel opening properties of curcumin may be responsible for TSM relaxation.

Role of TRPP2 in mouse airway smooth muscle tension and respiration.

The transient receptor potential polycystin-2 (TRPP2) is encoded by the Pkd2 gene, and mutation of this gene can cause autosomal dominant polycystic kidney disease (ADPKD). Some patients with ADPKD experience extrarenal manifestations, including radiologic and clinical bronchiectasis. We hypothesized that TRPP2 may regulate airway smooth muscle (ASM) tension. Thus, we used smooth muscle-Pkd2 conditional knockout (Pkd2SM-CKO) mice to investigate whether TRPP2 regulated ASM tension and whether TRPP2 deficiency contributed to bronchiectasis associated with ADPKD. Compared with wild-type mice, Pkd2SM-CKO mice breathed more shallowly and faster, and their cross-sectional area ratio of bronchi to accompanying pulmonary arteries was higher, suggesting that TRPP2 may regulate ASM tension and contribute to the occurrence of bronchiectasis in ADPKD. In a bioassay examining isolated tracheal ring tension, no significant difference was found for high-potassium-induced depolarization of the ASM between the two groups, indicating that TRPP2 does not regulate depolarization-induced ASM contraction. By contrast, carbachol-induced contraction of the ASM derived from Pkd2SM-CKO mice was significantly reduced compared with that in wild-type mice. In addition, relaxation of the carbachol-precontracted ASM by isoprenaline, a ß-adrenergic receptor agonist that acts through the cAMP/adenylyl cyclase pathway, was also significantly attenuated in Pkd2SM-CKO mice compared with that in wild-type mice. Thus, TRPP2 deficiency suppressed both contraction and relaxation of the ASM. These results provide a potential target for regulating ASM tension and for developing therapeutic alternatives for some ADPKD complications of the respiratory system or for independent respiratory disease, especially bronchiectasis.

Structural and functional alterations of the tracheobronchial tree after left upper pulmonary lobectomy for lung cancer.

BACKGROUND: Pulmonary lobectomy has been a well-established curative treatment method for localized lung cancer. After left upper pulmonary lobectomy, the upward displacement of remaining lower lobe causes the distortion or kink of bronchus, which is associated with intractable cough and breathless. However, the quantitative study on structural and functional alterations of the tracheobronchial tree after lobectomy has not been reported. We sought to investigate these alterations using CT imaging analysis and computational fluid dynamics (CFD) method. METHODS: Both preoperative and postoperative CT images of 18 patients who underwent left upper pulmonary lobectomy are collected. After the tracheobronchial tree models are extracted, the angles between trachea and bronchi, the surface area and volume of the tree, and the cross-sectional area of left lower lobar bronchus are investigated. CFD method is further used to describe the airflow characteristics by the wall pressure, airflow velocity, lobar flow rate, etc. RESULTS: It is found that the angle between the trachea and the right main bronchus increases after operation, but the angle with the left main bronchus decreases. No significant alteration is observed for the surface area or volume of the tree between pre-operation and post-operation. After left upper pulmonary lobectomy, the cross-sectional area of left lower lobar bronchus is reduced for most of the patients (15/18) by 15-75%, especially for 4 patients by more than 50%. The wall pressure, airflow velocity and pressure drop significantly increase after the operation. The flow rate to the right lung increases significantly by 2-30% (but there is no significant difference between each lobe), and the flow rate to the left lung drops accordingly. Many vortices are found in various places with severe distortions. CONCLUSIONS: The favorable and unfavorable adaptive alterations of tracheobronchial tree will occur after left upper pulmonary lobectomy, and these alterations can be clarified through CT imaging and CFD analysis. The severe distortions at left lower lobar bronchus might exacerbate postoperative shortness of breath.

Dynamic Upper Airway Imaging during Wakefulness in Obese Subjects with and without Sleep Apnea.

RATIONALE: Obesity is a major risk factor for obstructive sleep apnea. Although greater dimensional changes in the upper airway during wake respiration have been noted in patients with apnea compared with control subjects, whether these differences remain in the presence of obesity is unknown. OBJECTIVES: To evaluate upper airway anatomic characteristics and airway compliance (distensibility) in obese subjects with obstructive sleep apnea compared with obese control subjects. METHODS: Dynamic magnetic resonance imaging was performed in 157 obese subjects with apnea and 46 obese control subjects during wakefulness in the midsagittal and three axial upper airway regions (retropalatal, retroglossal, epiglottal). Differences in measurements between subjects with apnea and control subjects, and correlations with apnea-hypopnea index among subjects with apnea, were examined. MEASUREMENTS AND MAIN RESULTS: Measurements included airway areas and linear dimensions. Subject-specific coefficients of variation were calculated to examine variability in airway size. Controlling for covariates, the retropalatal area during respiration was significantly smaller in subjects with apnea than control subjects, based on the average (P = 0.003), maximum (P = 0.004), and minimum (P = 0.001) airway area. Airway narrowing was observed in anteroposterior and lateral dimensions (adjusted P < 0.05). Results were similar in an age, sex, and body mass index-matched subsample. There were significant correlations between apnea-hypopnea index and dynamic measures of airway caliber in the retropalatal and retroglossal regions among subjects with apnea. CONCLUSIONS: Upper airway caliber during respiration was significantly narrower in obese subjects with apnea than obese control subjects in the retropalatal region. These findings provide further evidence that retropalatal airway narrowing plays an important role in the pathogenesis of obstructive sleep apnea in obese subjects.