Lung Size Research Articles

Postoperative pulmonary artery stenosis in lung transplantation recipients: review of case series

Background: Postoperative pulmonary artery stenosis (PAS) is rare complication that can appear lung transplant recipients due to inappropriate donor to recipient lung size matching. In this study, we retrospectively reviewed patients who were diagnosed PAS after lung transplantation. Methods: Medical records were retrospectively reviewed in the group of lung transplant recipients from 2012 to 2019 in Sever ance Hospital, Korea. Results: Among 267 recipients who underwent lung transplantation from October 2012 to December 2019, 12 patients were diagnosed PAS and treated accordingly. Four patients received surgical treatment. Six patients were successfully received in terventional therapy: pulmonary angioplasty or pulmonary artery (PA) stent insertion. Two patients were under observation due to benign progress. Mortality were observed in three patients, and one death was related to PAS. Three patients had either left or right donor-to-recipient PA mismatch and four patients had donor lung size mismatch. After excluding the mortality and ob servant cases, eight patients had relief of symptoms and five patients showed increased outcome in before-and-after perfusion scan. Most common initial manifestation was progressive dyspnea and chest discomfort (seven cases), while median time of diagnosis-to-treatment was 36 days. Seven patients were diagnosed PAS in 2 weeks from day of lung transplantation. In this group, most common clue for diagnosis was acute change of chest X-ray (increased haziness) and hypoxemia. On contrary, five patients who were diagnosed after 2 weeks tended to not show acute change in chest X-ray, rather most common phenomenon was progressive dyspnea, chest discomfort, and prolonged pneumonia. Conclusions: PAS after lung transplantation can be managed by either PA intervention or surgical approach depending on cir cumstance of patients. Mortality were most likely associated with underlying patient’s condition such as septic shock. Progres sive dyspnea, chest discomfort, hypoxemia, and left lung haziness in chest X-ray may indicate PAS. Early diagnosis-to-treatment is vital for favorable outcome.

Postmortem Changes in pH, Color, Drip Loss, and Non-Protein Nitrogen in Beef Liver and Lungs During Storage in Refrigerator

Beef offal are consumed by people in some countries specifically in Asia. Beef liver and lungs are favorite food which are used as meat in traditional food. The objective of this study was to determine the postmortem changes in pH, color, drip loss, and non-protein nitrogen (NPN) content in beef liver and lungs during storage in refrigerator (3-4 ºC) until 5 d (120 h) after slaughter. The beef liver and lungs were collected from the abattoir and transported in cool box (<7 ºC) to the laboratory within 3 hours. The samples size of beef liver and lungs were 20 for each observation time. In the laboratory the beef liver and lungs were measured directly for pH value, color (L*, a*, and b*), drip loss, and NPN content at 4 h postmortem (pm) and afterwards every beef liver sample was sliced into 5 pieces of 100-120 g and stored in chiller of 3-4 ºC. The measurement of pH, color (L*, a*, and b* values), drip loss, and NPN content were conducted at 4 h, 24 h, 48 h, 72 h, 96 h, and 120 h postmortem. Data were analyzed descriptively and by comparing the 95% confidence interval of mean of each observation. The results showed that pH, color, drip loss, and NPN content in beef lungs were higher than the values in beef liver. The pH of beef liver and lungs declines until 96 h pm and 48 h pm, respectively. The L*, a*, and b* values of beef liver and lungs increased in general during storage. Drip loss and NPN in beef liver and lungs tended to increase significantly during storage. From this study the pH value and NPN can be used to determine the freshness of beef liver and lungs.

Lung and fissure shape is associated with age in healthy never-smoking adults aged 20\u201390 years

Lung shape could hold prognostic information for age-related diseases that affect lung tissue mechanics. We sought to quantify mean lung shape, its modes of variation, and shape associations with lung size, age, sex, and Body Mass Index (BMI) in healthy subjects across a seven-decade age span. Volumetric computed tomography from 83 subjects (49 M/34 F, BMI 24.7 pm 2.7) was used to derive two statistical shape models using a principal component analysis. One model included, and the other controlled for, lung volume. Volume made the strongest contribution to shape when it was included. Shape had a strong relationship with age but not sex when volume was controlled for, and BMI had only a small but significant association with shape. The first principal shape mode was associated with decrease in the antero-posterior dimension from base to apex. In older subjects this was rapid and obvious, whereas younger subjects had relatively more constant dimension. A shift of the fissures of both lungs in the basal direction was apparent for the older subjects, consistent with a change in tissue elasticity with age. This study suggests a quantifiable structure-function relationship for the healthy adult lung that can potentially be exploited as a normative description against which abnormal can be compared.

Розміри легень при різних анатомічних варіантах вродженої діафрагмальної грижі у плода

The objective: to compare lung indices in fetuses with different anatomical variants of left-sided congenital diaphragmatic hernia, determined by two-dimensional ultrasound examination. Materials and methods. Data from 157 ultrasound examinations in 136 fetuses as patients with the most typical anatomical variants of left-sided diaphragmatic hernia were analyzed. The area of the lungs and the herniated liver were measured in the standard cross section of fetal thorax, at the level of a four-chamber view, with following calculation of prognostic indices. Comparison of indices’ means in groups depending on the abdominal organs herniated into fetal chest was performed using Student’s t-test. Results. The most numerous group in our study was one with herniation of the liver, stomach and intestines (62.5%). Significantly lower values of all lung indices were found in this group (p≤0.0001). In particular, observed-to-expected area ratio equaled to 35.59±8.8 and 31.73±10.51 in these fetuses in II and III trimesters respectively. In fetuses with intestines herniation, this index was 60.67±10.93 and 57.37±7.98, in fetuses with stomach and intestines herniation – 53.20±7.02 and 51.77±9.57 in II and III trimesters, respectively. Differential analysis of lung indices depending on the degree of liver herniation showed the presence of statistically highly significant difference in both second and third trimesters. In the group with mild liver herniation, the largest lung sizes and indices were determined, which were similar to values registered in groups without hepatic herniation. The lowest values of all lung indices were registered in the group with severe liver herniation. Conclusions. The anatomical variant of left diaphragmatic hernia with herniation of liver, stomach and intestines into thorax was the most common among our study population; in this group the lowest values of term-independent lung indices were observed. However, this group turned out to be heterogeneous: with different degrees of liver herniation, different degrees of pulmonary hypoplasia were found. Significant differences in lung indices found in II trimester can become a basis for early assessment of the severity of pathology and prediction of postnatal outcome. Keywords: congenital diaphragmatic hernia, liver herniation, pulmonary hypoplasia, lung size, prenatal diagnosis.

Enhanced super-resolution reconstruction of T1w time-resolved 4DMRI in low-contrast tissue using 2-step hybrid deformable image registration.

PurposeDeformable image registration (DIR) in low‐contrast tissues is often suboptimal because of low visibility of landmarks, low driving‐force to deform, and low penalty for misalignment. We aim to overcome the shortcomings for improved reconstruction of time‐resolved four‐dimensional magnetic resonance imaging (TR‐4DMRI).Methods and MaterialsSuper‐resolution TR‐4DMRI reconstruction utilizes DIR to combine high‐resolution (highR:2x2x2mm3) breath‐hold (BH) and low‐resolution (lowR:5x5x5mm3) free‐breathing (FB) 3D cine (2Hz) images to achieve clinically acceptable spatiotemporal resolution. A 2‐step hybrid DIR approach was developed to segment low‐dynamic‐range (LDR) regions: low‐intensity lungs and high‐intensity “bodyshell” (=body‐lungs) for DIR refinement after conventional DIR. The intensity in LDR regions was renormalized to the full dynamic range (FDR) to enhance local tissue contrast. A T1‐mapped 4D XCAT digital phantom was created, and seven volunteers and five lung cancer patients were scanned with two BH and one 3D cine series per subject to compare the 1‐step conventional and 2‐step hybrid DIR using: (a) the ground truth in the phantom, (b) highR‐BH references, which were used to simulate 3D cine images by down‐sampling and Rayleigh‐noise‐adding, and (c) cross‐verification between two TR‐4DMRI images reconstructed from two BHs. To assess DIR improvement, 8‐17 blood vessel bifurcations were used in volunteers, and lung tumor position, size, and shape were used in phantom and patients, together with the voxel intensity correlation (VIC), structural similarity (SSIM), and cross‐consistency check (CCC).ResultsThe 2‐step hybrid DIR improves contrast and DIR accuracy. In volunteers, it improves low‐contrast alignment from 6.5 ± 1.8 mm to 3.3 ± 1.0 mm. In phantom, it improves tumor center of mass alignment (COM = 1.3 ± 0.2 mm) and minimizes DIR directional difference. In patients, it produces almost‐identical tumor COM, size, and shape (dice> 0.85) as the reference. The VIC and SSIM are significantly increased and the number of CCC outliers are reduced by half.ConclusionThe 2‐step hybrid DIR improves low‐contrast‐tissue alignment and increases lung tumor fidelity. It is recommended to adopt the 2‐step hybrid DIR for TR‐4DMRI reconstruction.

Progress of mechanical power in the intensive care unit.

Mechanical power of ventilation, currently defined as the energy delivered from the ventilator to the respiratory system over a period of time, has been recognized as a promising indicator to evaluate ventilator-induced lung injury and predict the prognosis of ventilated critically ill patients. Mechanical power can be accurately measured by the geometric method, while simplified equations allow an easy estimation of mechanical power at the bedside. There may exist a safety threshold of mechanical power above which lung injury is inevitable, and the assessment of mechanical power might be helpful to determine whether the extracorporeal respiratory support is needed in patients with acute respiratory distress syndrome. It should be noted that relatively low mechanical power does not exclude the possibility of lung injury. Lung size and inhomogeneity should also be taken into consideration. Problems regarding the safety limits of mechanical power and contribution of each component to lung injury have not been determined yet. Whether mechanical power-directed lung-protective ventilation strategy could improve clinical outcomes also needs further investigation. Therefore, this review discusses the algorithms, clinical relevance, optimization, and future directions of mechanical power in critically ill patients.

Synchronized Inflations Generate Greater Gravity-Dependent Lung Ventilation in Neonates

To describe the regional distribution patterns of tidal ventilation within the lung during mechanical ventilation that is synchronous or asynchronous with an infant's own breathing effort. Intubated infants receiving synchronized mechanical ventilation at The Royal Children's Hospital neonatal intensive care unit were studied. During four 10-minute periods of routine care, regional distribution of tidal volume (VT; electrical impedance tomography), delivered pressure, and airway flow (Florian Respiratory Monitor) were measured for every inflation. Post hoc, each inflation was then classified as synchronous or asynchronous from video data of the ventilator screen, and the distribution of absolute VT and delivered ventilation characteristics determined. In total, 2749 inflations (2462 synchronous) were analyzed in 19 infants; mean (SD) age 28 (30) days, gestational age 35 (5) weeks. Synchronous inflations were associated with a shorter respiratory cycle (P=.004) and more homogenous VT (center of ventilation) along the right (0%) to left (100%) lung plane; 45.3 (8.6)% vs 48.8 (9.4)% (uniform ventilation 46%). The gravity-dependent center of ventilation was a mean (95% CI) 2.1 (-0.5, 4.6)% toward the dependent lung during synchronous inflations. Tidal ventilation relative to anatomical lung size was more homogenous during synchronized inflations in the dependent lung. Synchronous mechanical ventilator lung inflations generate more gravity-dependent lung ventilation and more uniform right-to-left ventilation than asynchronous inflations.

A deep Residual U-Net convolutional neural network for automated lung segmentation in computed tomography images

To improve the early diagnosis and treatment of lung diseases automated lung segmentation from CT images is a crucial task for clinical decision. The segmentation of the lung region from the CT scans is a very challenging task due to the irregular shape and size of lungs, low contrast and fuzzy boundaries of the lung. The manual segmentation of lung CT images is a laborious task. Therefore, various approaches are suggested by the researcher in the recent past for the automated lung segmentation. However, the existing approaches either utilize low-level handcraft features or CNN based Fully Convolutional Networks. The low-level hand-craft feature-based approaches lead to poor generalization, while the shallower networks are unable to extract more discriminative features. Hence, in this study, we have implemented a deep learning-based architecture called Residual U-Net with a false-positive removal algorithm for lung CT segmentation. Here, we have suggested that learning from a substantially deeper network with residual units can extract more discriminative feature representation as compared to shallow network for lung segmentation. To take full advantage of the deeper network, we have utilized a set of schemes to ensure efficient training. First, we have implemented a U-Net architecture with residual block to overcome the problem of performance degradation. Further, various data augmentation techniques are utilized to improve the generalization capability of the proposed method. The experimental results show that the proposed method achieved competitive results over the existing methods with DSC of 98.63%, 99.62% and 98.68% for LUNA16, VESSEL12 and HUG-ILD dataset respectively.

Association of Dysanapsis With Chronic Obstructive Pulmonary Disease Among Older Adults

Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), yet much of COPD risk remains unexplained. To determine whether dysanapsis, a mismatch of airway tree caliber to lung size, assessed by computed tomography (CT), is associated with incident COPD among older adults and lung function decline in COPD. A retrospective cohort study of 2 community-based samples: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, which involved 2531 participants (6 US sites, 2010-2018) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD), which involved 1272 participants (9 Canadian sites, 2010-2018), and a case-control study of COPD: the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which involved 2726 participants (12 US sites, 2011-2016). Dysanapsis was quantified on CT as the geometric mean of airway lumen diameters measured at 19 standard anatomic locations divided by the cube root of lung volume (airway to lung ratio). Primary outcome was COPD defined by postbronchodilator ratio of forced expired volume in the first second to vital capacity (FEV1:FVC) less than 0.70 with respiratory symptoms. Secondary outcome was longitudinal lung function. All analyses were adjusted for demographics and standard COPD risk factors (primary and secondhand tobacco smoke exposures, occupational and environmental pollutants, and asthma). In the MESA Lung sample (mean [SD] age, 69 years [9 years]; 1334 women [52.7%]), 237 of 2531 participants (9.4%) had prevalent COPD, the mean (SD) airway to lung ratio was 0.033 (0.004), and the mean (SD) FEV1 decline was -33 mL/y (31 mL/y). Of 2294 MESA Lung participants without prevalent COPD, 98 (4.3%) had incident COPD at a median of 6.2 years. Compared with participants in the highest quartile of airway to lung ratio, those in the lowest had a significantly higher COPD incidence (9.8 vs 1.2 cases per 1000 person-years; rate ratio [RR], 8.12; 95% CI, 3.81 to 17.27; rate difference, 8.6 cases per 1000 person-years; 95% CI, 7.1 to 9.2; P < .001) but no significant difference in FEV1 decline (-31 vs -33 mL/y; difference, 2 mL/y; 95% CI, -2 to 5; P = .30). Among CanCOLD participants (mean [SD] age, 67 years [10 years]; 564 women [44.3%]), 113 of 752 (15.0%) had incident COPD at a median of 3.1 years and the mean (SD) FEV1 decline was -36 mL/y (75 mL/y). The COPD incidence in the lowest airway to lung quartile was significantly higher than in the highest quartile (80.6 vs 24.2 cases per 1000 person-years; RR, 3.33; 95% CI, 1.89 to 5.85; rate difference, 56.4 cases per 1000 person-years; 95% CI, 38.0 to 66.8; P<.001), but the FEV1 decline did not differ significantly (-34 vs -36 mL/y; difference, 1 mL/y; 95% CI, -15 to 16; P=.97). Among 1206 SPIROMICS participants (mean [SD] age, 65 years [8 years]; 542 women [44.9%]) with COPD who were followed up for a median 2.1 years, those in the lowest airway to lung ratio quartile had a mean FEV1 decline of -37 mL/y (15 mL/y), which did not differ significantly from the decline in MESA Lung participants (P = .98), whereas those in highest quartile had significantly faster decline than participants in MESA Lung (-55 mL/y [16 mL/y ]; difference, -17 mL/y; 95% CI, -32 to -3; P = .004). Among older adults, dysanapsis was significantly associated with COPD, with lower airway tree caliber relative to lung size associated with greater COPD risk. Dysanapsis appears to be a risk factor associated with COPD.

Effect of mechanical power on intensive care mortality in ARDS patients

BackgroundIn ARDS patients, mechanical ventilation should minimize ventilator-induced lung injury. The mechanical power which is the energy per unit time released to the respiratory system according to the applied tidal volume, PEEP, respiratory rate, and flow should reflect the ventilator-induced lung injury. However, similar levels of mechanical power applied in different lung sizes could be associated to different effects. The aim of this study was to assess the role both of the mechanical power and of the transpulmonary mechanical power, normalized to predicted body weight, respiratory system compliance, lung volume, and amount of aerated tissue on intensive care mortality.MethodsRetrospective analysis of ARDS patients previously enrolled in seven published studies. All patients were sedated, paralyzed, and mechanically ventilated.After 20 min from a recruitment maneuver, partitioned respiratory mechanics measurements and blood gas analyses were performed with a PEEP of 5 cmH2O while the remaining setting was maintained unchanged from the baseline. A whole lung CT scan at 5 cmH2O of PEEP was performed to estimate the lung gas volume and the amount of well-inflated tissue.Univariate and multivariable Poisson regression models with robust standard error were used to calculate risk ratios and 95% confidence intervals of ICU mortality.ResultsTwo hundred twenty-two ARDS patients were included; 88 (40%) died in ICU. Mechanical power was not different between survivors and non-survivors 14.97 [11.51–18.44] vs. 15.46 [12.33–21.45] J/min and did not affect intensive care mortality. The multivariable robust regression models showed that the mechanical power normalized to well-inflated tissue (RR 2.69 [95% CI 1.10–6.56], p = 0.029) and the mechanical power normalized to respiratory system compliance (RR 1.79 [95% CI 1.16–2.76], p = 0.008) were independently associated with intensive care mortality after adjusting for age, SAPS II, and ARDS severity. Also, transpulmonary mechanical power normalized to respiratory system compliance and to well-inflated tissue significantly increased intensive care mortality (RR 1.74 [1.11–2.70], p = 0.015; RR 3.01 [1.15–7.91], p = 0.025).ConclusionsIn our ARDS population, there is not a causal relationship between the mechanical power itself and mortality, while mechanical power normalized to the compliance or to the amount of well-aerated tissue is independently associated to the intensive care mortality. Further studies are needed to confirm this data.

Cause of mortality in patients with lung cancer and brain metastasis.

e21743 Background: Lung cancer is the most common cause of cancer-related mortality and most deaths are associated with metastatic disease, with brain being a common site. Historically, whole brain radiation therapy was the treatment of choice and resulted in median survivals in the range of 6 months. There is no consensus in management of patients who have brain metastasis with systemic disease.We aim to evaluate patients with brain metastasis from lung cancer for cause of death, to investigate whether patients died from central nervous system (CNS) progression or systemic disease or other/undetermined causes. Our hypothesis is that most deaths in contemporary patients with brain metastasis in lung cancer are due to systemic disease, and less commonly due to CNS progression. Methods: In this retrospective observational study, we did a chart review of all adult patients with non-small cell lung cancer and brain metastasis or leptomeningeal disease, who received treatment at Maimonides Cancer Center between 2010 and 2017. Patients with unavailable or incomplete medical records were excluded. Baseline characteristics, pathological factors of the tumor and cause of death was collected from the chart. The cause of death was categorized into systemic and brain causes, and difference in characteristics of patients and tumor were studied. Results: A total of 132 patients were included and their charts were reviewed. Out of 132, 96 could have a clear cause of death categorized into systemic or brain causes, the rest were either mixed or uncategorized. We found that 33% patients died of brain metastasis, and related causes, whereas 67% died of systemic disease progression. There were no different in the two groups in terms of gender, smoking status, histology, size of lung lesion, or number and size of brain lesion. The patients who died of brain metastasis had a significantly higher age, and worse Eastern Cooperative Oncology Group status. Interestingly, the patients who died of systemic causes more commonly had adrenal metastasis (12 vs 0) which was statistically significant, and liver (14 vs 3) metastasis which was not statistically significant. Conclusions: Two-thirds of patients with brain metastases died of systemic disease rather than CNS progression. This may reflect improvements in systemic and local therapies to forestall cancer progression in the CNS. This finding suggests that delaying systemic therapy for CNS treatment may negatively impact overall cancer control. More research needs to be done to answer this question with certainty, including prospective clinical trials.

Pnömonili Hastalarda ve Sağlıklı Bireylerde Akciğer Boyutunun Değerlendirilmesi

In recent years, medical image segmentation studies and the need for this issue are increasing rapidly. Semi or fully automatic segmentation of the region to be diagnosed in medical images provides doctors with an important convenience for diagnosis. Especially in some countries where there is a lack of a doctor, it will be provided with a fully automatic segmentation method to assist the treatment without a doctor. In this study, lung x-ray images of patients with pneumonia and healthy individuals were studied. X-ray images are advantageous because they are cheaper and easier to interpret than other imaging methods. X-ray images were taken from the ready dataset and the image set consists of chest x-ray images of children under 5 years old. A total of 15 individuals (5 healthy, 5 pneumonia (virus) patients, 5 pneumonia (bacteria) patients) were studied from the data set received. MATLAB program was used for segmentation of lung areas. For segmentation, the images were first reduced to size after being taken to MATLAB. Then, by increasing the contrast of the images, filtering and thresholding process was done with appropriate filter design. Image Segmenter Tool was used for thresholding process. Unlike other studies, active contour method was used to perform lung segmentation. Active contour operation provides energy minimization by drawing skews inside and outside the lung boundaries, iteration continues until equilibrium is achieved, so that the lung boundaries are determined. After active contour procedure, morphological procedures were applied, lung areas were removed and areas were calculated. As a result, semi-automatic segmentation was carried out using the active contour model along with image processing procedures. A significant difference was obtained between the lung sizes of patients and healthy individuals. It is aimed to develop a fully automatic segmentation algorithm that can be generalized for each patient in the future.

The Prevalence of Expiratory Flow Limitation in Youth Elite Male Cyclists.

Twelve ET youth male cyclists (16.3 ± 1.0 yr (13-18 yr), 176.5 ± 6.2 cm, 64.2 ± 5.9 kg) and 12 CON subjects (17.6 ± 2.2 yr (13-18 yr), 177.9 ± 7.1 cm, 74.8 ± 11.2 kg) completed an incremental exercise test to determine peak oxygen consumption (V˙O2peak) on a cycle ergometer. Maximal flow volume loops (MFVL), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, forced expiratory flow between 25% and 75% of FVC, and peak expiratory flow were assessed before and after exercise, with inspiratory capacity maneuvers and dyspnea ratings measured in the last 20 s of each stage. EFL was quantified as the percentage of the expiratory tidal volume that overlapped with the maximal flow volume loop. V˙O2peak, dyspnea ratings at peak, and ventilation were higher in the ET compared with CON group (P < 0.05). The ET group experienced greater EFL prevalence at V˙O2peak, with 11 of 12 subjects exhibiting EFL compared with 5 of 12 subjects in the CON group (P = 0.014). When matched for absolute ventilation of 20, 40, 60, 80, and 100 L·min, there were no differences in EFL severity between the ET and CON groups (P = 0.473). Elite youth male cyclists have a greater prevalence of EFL at maximal exercise than do CON subjects who are similar in age, height, and lung size. Future research should determine whether EFL in youth ET male cyclists may limit their exercise performance.

Thermal and oxygen conditions during development cause common rough woodlice (Porcellio scaber) to alter the size of their gas-exchange organs.

Terrestrial isopods have evolved pleopodal lungs that provide access to the rich aerial supply of oxygen. However, isopods occupy conditions with wide and unpredictable thermal and oxygen gradients, suggesting that they might have evolved adaptive developmental plasticity in their respiratory organs to help meet metabolic demand over a wide range of oxygen conditions. To explore this plasticity, we conducted an experiment in which we reared common rough woodlice (Porcellio scaber) from eggs to maturation at different temperatures (15 and 22°C) combined with different oxygen levels (10% and 22% O2). We sampled animals during development (only females) and then examined mature adults (both sexes). We compared woodlice between treatments with respect to the area of their pleopod exopodites (our proxy of lung size) and the shape of Bertalanffy's equations (our proxy of individual growth curves). Generally, males exhibited larger lungs than females relative to body size. Woodlice also grew relatively fast but achieved a decreased asymptotic body mass in response to warm conditions; the oxygen did not affect growth. Under hypoxia, growing females developed larger lungs compared to under normoxia, but only in the late stage of development. Among mature animals, this effect was present only in males. Woodlice reared under warm conditions had relatively small lungs, in both developing females (the effect was increased in relatively large females) and among mature males and females. Our results demonstrated that woodlice exhibit phenotypic plasticity in their lung size. We suggest that this plasticity helps woodlice equilibrate their gas exchange capacity to differences in the oxygen supply and metabolic demand along environmental temperature and oxygen gradients. The complex pattern of plasticity might indicate the effects of a balance between water conservation and oxygen uptake, which would be especially pronounced in mature females that need to generate an aqueous environment inside their brood pouch.

Does sociality drive diversity and composition of airway microbiota in cetaceans?

The number of social contacts of mammals is positively correlated with the diversity of their gut microbes. There is some evidence that sociality also affects microbes in the respiratory tract. We tested whether the airway microbiota of cetacean species differ depending on the whales' level of sociality. We sampled the blow of blue (Balaenoptera musculus), grey (Eschrichtius robustus), humpback (Megaptera novaeangliae) and long-finned pilot whales (PWs) (Globicephala melas) and analysed the blow microbiota by barcode tag sequencing targeting the V4 region of the bacterial 16S rRNA gene. Humpback whales (HWs) show higher levels of sociality than blue (BW) and grey (GW), while PWs are the most gregarious among the four species. The blow samples of the HWs showed the highest richness and diversity. HWs were also the only species with a species-specific clustering of their microbial community composition and a relatively large number of core taxa. Therefore, we conclude that it cannot be sociality alone shaping the diversity and composition of airway microbiota. We suggest the whale species' lung volume and size of the plume of exhaled air as an additional factor impacting the transmission potential of blow microbiota from one individual whale to another.

Proteomics Analysis of Circulating Extracellular Vesicles Isolated from Plasma of Human Lung Transplant Recipients

We demonstrated induction of circulating exosomes in lung transplant recipients (LTxRs) with acute/chronic rejection (bronchiolitis obliterans syndrome [BOS]) containing donor human leukocyte antigen and lung self-antigens (SAgs) (Kα-1 Tubulin, Collagen V), costimulatory molecules (CD80, CD86), transcription factors (NFkB, 20S proteasome) (Am J Transplant 17(2):474-484, 2017). In the current study, we identified unique proteomic signatures in circulating extracellular vesicles (EVs) that can differentiate human LTxRs with acute rejection (AR), BOS, respiratory viral infection (RVI), and stable. EVs were isolated using ultracentrifugation from LTxRs plasma (stable, AR, BOS or RVI) following transplant. EVs were characterized for the presence of lung SAgs (Kα-1 Tubulin, Collagen V) and size (50-200nm) was determined using NanoSight. EV protein cargoes were prepared for shotgun proteomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We identified unique proteins (2 AR, 24 BOS, 4 RVI, 8 stable cohort) using LC-MS/MS. Differential analysis of the proteins from AR, BOS and RVI to stable yielded significant unique proteins (p-value <.05, fold-change >2) in each clinical cohort (27 AR, 2 BOS, 2 RVI). EVs from AR contained proteins involved in immunoglobulin, complement regulation, innate and adaptive immune response pathways. EVs from BOS revealed enrichment of immunoglobulin receptors and carboxypeptidase N catalytic chain. EVs from RVI were enriched for macrophage stimulating factor. Our results demonstrate unique signatures in acute/chronic rejection and RVI highlighting complex immune mechanisms underlying lung allograft rejection. Presence of complement proteins and immunoglobulins in circulating EVs from AR can be helpful in differentiating cellular rejection with a mixed phenotype (cellular and humoral). We identified immunoglobulins and complement proteins in BOS in support of significance of Abs in the pathogenesis of BOS. Macrophage stimulating factor contained in EVs specific to RVI can be useful for the differential diagnosis of RVI from AR. To conclude, proteomic signatures of circulating EVs from LTxRs provided insights into immunological mechanisms at play in graft rejection and RVI leading to increased risk for chronic lung allograft dysfunction.

Abnormal Pulmonary Lymphatic Flow in Patients With Lymphatic Anomalies and Respiratory Compromise

Pulmonary involvement in lymphatic anomalies (LA) is associated with significant morbidity and mortality. Dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) is capable of imaging the lymphatic system in a variety of pulmonary lymphatic disorders. The objective of this study is to describe the central lymphatic anatomy in patients with LA and pulmonary involvement on DCMRL. This prospective observational study enrolled 16 patients with LA (mean age, 17 years; range, 6-63 years; ratio of female to male patients, 9:7) with pulmonary involvement. All patients underwent DCMRL. The lymphatic system was assessed for the presence of mediastinal masses, interstitial lung disease, size and tortuosity of the thoracic duct (TD), and presence of abnormal pulmonary lymphatic flow. T2-weighted imaging showed the following: mediastinal soft tissue masses in 10 patients, diffuse pulmonary interstitial thickening in 13 patients, and bone involvement in 15 patients. DCMRL revealed abnormal pulmonary lymphatic flow in 14 of 16 patients. Abnormal pulmonary lymphatic flow originated from the TD in three of 14 patients, the retroperitoneum in six of 14 patients, and both the TD and retroperitoneum in four of 14 patients. In nine of 16 patients, the TD was dilated and tortuous. In two patients the TD was not identified, and in five patients it was normal. Abnormal pulmonary lymphatic flow/perfusion from the TD or retroperitoneum into the lung parenchyma occurred in the majority of patients in this study. These findings can explain the interstitial lung disease and chylothorax resulting in deterioration of respiratory function in these patients. Future studies will determine whether mechanical cessation of this abnormal flow can improve pulmonary function and prolong survival in patients with LA. Clinicaltrials.gov; No.: NCT02744027; URL: www.clinicaltrials.gov.

Gestation and lactation exposure to nicotine induces transient postnatal changes in lung alveolar development.

Harmful consequences of cigarette smoke (CS) exposure during lung development can already manifest in infancy. In particular, early life exposure to nicotine, the main component of CS, was shown to affect lung development in animal models. We aimed to characterize the effect of nicotine on alveoli formation. We analyzed the kinetics of normal alveolar development during the alveolarization phase and then looked at the effect of nicotine in a mouse model of gestational and early life exposure. Immunohistochemical staining revealed that the wave of cell proliferation [i.e., vascular endothelial cells, alveolar epithelial cells (AEC) type II and mesenchymal cell] occurs at postnatal day (pnd) 8 in control and nicotine-exposed lungs. However, FACS analysis of individual epithelial alveolar cells revealed nicotine-induced transient increase of AEC type I proliferation and decrease of vascular endothelial cell proliferation at pnd8. Furthermore, nicotine increased the percentage of endothelial cells at pnd2. Transcriptomic data also showed significant changes in nicotine samples compared with the controls on cell cycle-associated genes at pnd2 but not anymore at pnd16. Accordingly, the expression of survivin, involved in cell cycle regulation, also follows a different kinetics in nicotine lung extracts. These changes resulted in an increased lung size detected by stereology at pnd16 but no longer in adult age, suggesting that nicotine can act on the pace of lung maturation. Taken together, our results indicate that early life nicotine exposure could be harmful to alveolar development independently from other toxicants contained in CS.

E3 ubiquitin ligase MDM2 acts through p53 to control respiratory progenitor cell number and lung size.

The respiratory lineage initiates from the specification of NKX2-1+ progenitor cells that ultimately give rise to a vast gas-exchange surface area. How the size of the progenitor pool is determined and whether this directly impacts final lung size remains poorly understood. Here, we show that epithelium-specific inactivation of Mdm2, which encodes an E3 ubiquitin ligase, led to lethality at birth with a striking reduction of lung size to a single vestigial lobe. Intriguingly, this lobe was patterned and contained all the appropriate epithelial cell types. The reduction of size can be traced to the progenitor stage, when p53, a principal MDM2 protein degradation target, was transiently upregulated. This was followed by a brief increase of apoptosis. Inactivation of the p53 gene in the Mdm2 mutant background effectively reversed the lung size phenotype, allowing survival at birth. Together, these findings demonstrate that p53 protein turnover by MDM2 is essential for the survival of respiratory progenitors. Unlike in the liver, in which genetic reduction of progenitors triggered compensation, in the lung, respiratory progenitor number is a key determinant factor for final lung size.

Quantifying the mechanical work of breathing in men and women during rowing.

To quantify the mechanical work of breathing (Wb) during an indoor rowing test in men and women. Additionally, to compare sex-based differences in the Wb and its components through a rowing test. Fifteen collegiate rowers were recruited (8 women/7 men) and performed a 2000m rowing test on a rowing ergometer. Esophageal pressure was measured during exercise via balloon catheterization, after which pressure-volume curves were used to calculate total, inspiratory resistive and elastic, and total expiratory Wb. Men had significantly higher values of instantaneous and cumulative total Wb at and beyond 37.5% (430.4 ± 42.5 vs. 282.1 ± 45.1Jmin-1, P < 0.05) and 62.5% (1946.8 ± 150.9 vs. 1360.1 ± 197.2J, P < 0.05) total exercise time, respectively. However, when compared at the same minute ventilation, women had higher values of total (at and above ~ 140 Lmin-1), inspiratory resistive (at and above ~ 120 Lmin-1), and inspiratory elastic (at and above ~ 135 Lmin-1) Wb, whereas men presented higher total expiratory Wb compared to women at any ventilation. Although female rowers present higher relative values of inspiratory resistive and elastic Wb, their male counterparts develop greater ventilatory efforts during a 2000m rowing test, resulting in a larger total mechanical Wb. We interpret these findings to mean that the Wb reflects both anatomical (i.e., airways and lung sizes) and respiratory (i.e., minute ventilation) sex differences during rowing.