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Purpose: To investigate the impact of voluntary hypoventilation at low lung volumes (VHL) during upper body repeated sprints (RS) on performance, metabolic markers and muscle oxygenation in Brazilian Jiu-Jitsu (BJJ) athletes. Methods: Eighteen male well-trained athletes performed two randomized RS sessions, one with normal breathing (RSN) and another with VHL (RS-VHL), on an arm cycle ergometer, consisting of two sets of eight all-out 6-s sprints performed every 30 s. Peak (PPO), mean power output (MPO), and RS percentage decrement score were calculated. Arterial oxygen saturation (SpO2), heart rate (HR), gas exchange, and muscle oxygenation of the long head of the triceps brachii were continuously recorded. Blood lactate concentration ([La]) was measured at the end of each set. Bench press throw peak power (BPPP) was recorded before and after the RS protocol. Results: Although SpO2 was not different between conditions, PPO and MPO were significantly lower in RS-VHL. V ˙ E, HR, [La], and RER were lower in RS-VHL, and VO2 was higher in RS-VLH than in RSN. Muscle oxygenation was not different between conditions nor was its pattern of change across the RS protocol influenced by condition. [La] was lower in RS-VHL than in RSN after both sets. Conclusion: Performance was significantly lower in RS-VHL, even though SPO2 was not consistent with hypoxemia. However, the fatigue index was not significantly affected by VHL, nor was the neuromuscular upper body power after the RS-VHL protocol. Additionally, [La] was lower, and oxygen consumption was higher in RS-VHL, suggesting a higher aerobic contribution in this condition. [ABSTRACT FROM AUTHOR]

Purpose: Apnea duration is dependent on three factors: oxygen storage, oxygen consumption, hypoxia and hypercapnia tolerance. While current literature focuses on maximal apneas to improve apnea duration, apnea trained individuals use timed-repeated submaximal apneas, called "O2 and CO2 tables". These tables claim to accommodate the body to cope with hypoxia and hypercapnia, respectively. The aim of this study was twofold. First, to investigate the determinants of maximal apnea duration in apnea novices. Second, to compare physiologic responses to maximal apneas, O2 and CO2 tables. Methods: After medical screening, lung function test and hemoglobin mass measurement, twenty-eight apnea novices performed three apnea protocols in random order: maximal apneas, O2 table and CO2 table. During apnea, peripheral oxygen saturation (SpO2), heart rate (HR), muscle (mTOI) and cerebral (cTOI) tissue oxygenation index were measured continuously. End-tidal carbon dioxide (EtCO2) was measured before and after apneas. Results: Larger lung volumes, higher resting cTOI and lower resting EtCO2 levels correlated with longer apnea durations. Maximal apneas induced greater decreases in SpO2 (− 16%) and cTOI (− 13%) than O2 (− 8%; − 8%) and CO2 tables (− 6%; − 6%), whereas changes in EtCO2, HR and mTOI did not differ between protocols. Conclusion: These results suggest that, in apnea novices, O2 and CO2 tables did not induce a more profound hypoxia and hypercapnia, but a similar reduction in oxygen consumption than maximal apneas. Therefore, apnea novices should mainly focus on maximal apneas to improve hypoxia and hypercapnia tolerance. The use of specific lung training protocols can help to increase oxygen storage capacity. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a risk factor for the development of vascular disease, chronic kidney disease, retinopathy, and neuropathy. Diabetes is a co-morbid condition commonly present in patients with respiratory disorders but the extent to which it influences ventilatory capacity, gas exchange, and functional capacity is not well known. Research question Does the presence of diabetes contribute to impairment in spirometry, gas transfer, and exercise capacity? Methods: Retrospective analysis of all subjects who performed incremental cardio-pulmonary exercise testing (CPET) between 1988 and 2012 at McMaster University Medical Centre. The impact of diabetes on physiological outcomes and maximum power output (MPO) was assessed using stepwise multiple additive linear regression models including age, height, weight, sex, muscle strength, and previous myocardial infarct as co-variates, and was also stratified based on BMI categories. Results: 40,776 subjects were included in the analysis; 1938 (5%, 66% male) had diabetes. Diabetics were older (59 vs. 53 years), heavier (88.3 vs.78.0 kg), and had a higher BMI (31 vs. 27 kg/m2). The presence of diabetes was independently associated with a reduction in FEV1 (− 130 ml), FVC (− 220 ml), DLCO (− 1.52 ml/min/mmHg), and VA (− 340ml) but not KCO. Patients with diabetes achieved a lower % predicted MPO[diabetic subjects 70% predicted (670 kpm/min ± 95% CI 284) vs. 80% in non-diabetics (786 kpm/min ± 342), p < 0.001]. With the exception of KCO, these differences persisted across BMI categories and after adjusting for MI. Conclusion: The presence of diabetes is independently associated with weaker muscles, lower ventilatory and gas transfer capacity and translates to a lower exercise capacity. These differences are independent of age, height, weight, sex, and previous MI. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusion Radiation‐induced pneumonitis affects up to 33% of non‐small cell lung cancer (NSCLC) patients, with fatal pneumonitis occurring in 2% of patients. Pneumonitis risk is related to the dose and volume of lung irradiated. Clinical radiotherapy plans assume lungs are functionally homogeneous, but evidence suggests that avoidance of high‐functioning lung during radiotherapy can reduce the risk of radiation‐induced pneumonitis. Radiotherapy avoidance structures can be constructed based on high‐function regions indicated in a ventilation map, which can be produced from CT images.Existing methods of deriving such a CT ventilation image (CTVI) require the use of deformable image registration (DIR) of peak‐inhale and ‐exhale CT images, which is susceptible to inaccuracy for small or low‐intensity regions, and sensitive to image artefacts. To overcome these problems, we use a neural network to predict a ventilation map from breath‐hold CT (BHCT).We used the nnU‐Net pipeline to train five‐fold cross‐validated ensemble models to predict a ventilation map (CTVInnU‐Net). The training data were comprised of registered BHCT and Galligas PET images from 20 patients. Three training sets were created to ensure performance was averaged over different test patients. For each set, images from two randomly selected test patients were set aside, and models were trained on the remaining images. The ground truth was established by quantizing the Galligas PET images, assigning each voxel a label of high‐function (>70th percentile of intensity), medium‐function (between 30th and 70th percentile), or low‐function (<30th percentile). For comparison, we created a CTVI with a 2D U‐Net (CTVInnU‐Net‐2D), and with the Jacobian (CTVIJac) and Hounsfield Units (CTVIHU) DIR‐based methods which we quantized and labeled in the same way. The Dice similarity coefficient (DSC) and Hausdorff Distance 95th percentile (HD95) of each CTVI with the ground truth were measured separately for each lung function subregion.CTVInnU‐Net had the highest similarity to the quantized Galligas PET with a mean (range) DSC over all three categories of lung function at 0.68 (0.56 to 0.82), compared with 0.64 (0.47 to 0.75) for CTVInnU‐Net‐2D, 0.60 (0.38 to 0.73) for CTVIJac, and 0.56 (0.30 to 0.75) for CTVIHU. CTVInnU‐Net had the equal‐lowest spatial distance to the quantized Galligas PET averaged over the three categories, with HD95 of 22 mm (9 to 64 mm), compared with 23 mm (9 to 72 mm) for CTVInnU‐Net‐2D, 22 mm (12 to 63 mm) for CTVIJac, and 26 mm (12 to 58 mm) for CTVIHU.Our 3D neural network produces a quantized CTVI with higher similarity to the ground truth than the 2D U‐Net and DIR‐based Jacobian and HU methods. As it produces a quantized CTVI directly, CTVInnU‐Net avoids the need for thresholding to identify high‐function lung regions. With faster evaluation and improved accuracy, neural networks show promise for the clinical implementation of functional lung avoidance. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Four‐dimensional computed tomography (4DCT) is an es sential tool in radiation therapy. However, the 4D acquisition process may cause motion artifacts which can obscure anatomy and distort functional measurements from CT scans.We describe a deep learning algorithm to identify the location of artifacts within 4DCT images. Our method is flexible enough to handle different types of artifacts, including duplication, misalignment, truncation, and interpolation.We trained and validated a U‐net convolutional neural network artifact detection model on more than 23 000 coronal slices extracted from 98 4DCT scans. The receiver operating characteristic (ROC) curve and precision‐recall curve were used to evaluate the model's performance at identifying artifacts compared to a manually identified ground truth. The model was adjusted so that the sensitivity in identifying artifacts was equivalent to that of a human observer, as measured by computing the average ratio of artifact volume to lung volume in a given scan.The model achieved a sensitivity, specificity, and precision of 0.78, 0.99, and 0.58, respectively. The ROC area‐under‐the‐curve (AUC) was 0.99 and the precision‐recall AUC was 0.73. Our model sensitivity is 8% higher than previously reported state‐of‐the‐art artifact detection methods.The model developed in this study is versatile, designed to handle duplication, misalignment, truncation, and interpolation artifacts within a single image, unlike earlier models that were designed for a single artifact type. [ABSTRACT FROM AUTHOR]

Background: The ventilatory physiopathology of patients with interstitial lung disease (ILD) remains poorly understood. We aimed to personalize a mechanical simulator to model healthy and ILD profiles ventilation, and to evaluate the effect of spontaneous breathing on respiratory mechanics at rest and during exercise. Methods: In a 2-compartment lung simulator (ASL 5000®), we modeled 1 healthy and 3 ILD profiles, at rest and during exercise, based on physiological data from literature and patients. Measurements were: tidal volume, end-expiratory lung volume, driving pressure, transpulmonary driving pressure, dynamic alveolar strain, mechanical power, and time lag of inspiratory flow between compartments 1 and 2. Results: Healthy and ILD models were validated: maximum differences between real and simulated tidal volume were 5% (96 ml) and 6% (54 ml) at rest and during exercise respectively, considered clinically negligible. When we simulated lung inhomogeneity (compliance in compartment 1 > compartment 2), tidal volume, end-expiratory lung volume, driving pressure and mechanical power increased in compartment 1 and decreased in compartment 2. Driving transpulmonary pressure and dynamic alveolar strain increased in compartment 2 and decreased in compartment 1. Time lag of inspiratory flow between compartments 1 and 2 was positively correlated with a difference of compliance between compartments (r = 0.98, CI95% (0.9106; 0.9962), p < 0.0001). Conclusion: In this bench study, we personalized a mechanical simulator thatmodels the lung inhomogeneity and spontaneous breathing of healthy subjects and ILD patients at rest and during exercise. Our results suggest that lung inhomogeneity could increase lung vulnerability to volo-atelec-trauma mechanisms in ILD. Further physiological studies are needed to evaluate the impact of this vulnerability on acute or chronic ILD worsening. [ABSTRACT FROM AUTHOR]

Background: Respiratory compromise among ankylosing spondylitis (AS) patients is characterized by restrictive pulmonary function, leading to the need for a meticulous assessment of lung volume. Compared with conventional pulmonary function tests (PFTs), CT-based lung volume measurements have superior accuracy and are crucial for understanding functional limitations in AS. This study investigated the correlation between CT lung volume and PFT parameters in AS patients, with a focus on changes in CT parameters and lung volume in patients with compromised pulmonary function. Methods: A total of 79 AS patients were included, and their full-length radiographs, thoracic CT scans, and PFT data were analysed. Specialized software was used to estimate the total and lobar lung volumes from the CT scans. The relationship between lung volume and PFT results was examined, and a multiple linear regression model was constructed to determine the influence of radiographic and CT parameters on total lung volume (TLV). Patients were classified into normal or impaired pulmonary function groups based on PFT outcomes, thus facilitating comparative analyses of radiographic and CT parameters and lung volumes between these groups. Results: Among the 79 AS patients, 19 had normal function, 4 had mixed dysfunction, and 56 experienced restrictive dysfunction. PFT parameters, including FVC, FEV1, TLC, FEV1%, and TLC%, showed varying correlations with TLV and individual lobe volume. Patients with compromised pulmonary function exhibited more pronounced spinal kyphosis and experienced a decline in TLV. Multiple regression analysis revealed that lung height and horizontal and vertical lung diameters independently influenced TLV. Notably, a decrease in lung height was observed in patients with impaired pulmonary function, whereas the horizontal and vertical diameters of the lungs remained stable. Conclusions: In AS patients, TLV was found to be correlated with pulmonary function, particularly parameter such as FVC, FEV1, and TLC. A significant reduction in TLV was observed in those with impaired pulmonary function, with the primary contributing factor being a decrease in lung height. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of a repeated-sprint training in hypoxia induced by voluntary hypoventilation at low lung volume (RSH-VHL) including end-expiratory breath holding (EEBH) of maximal duration. Methods: Over a 4-week period, twenty elite judo athletes (10 women and 10 men) were randomly split into two groups to perform 8 sessions of rowing repeated-sprint exercise either with RSH-VHL (each sprint with maximal EEBH) or with unrestricted breathing (RSN, 10-s sprints). Before (Pre-), 5 days after (Post-1) and 12 days after (Post-2) the last training session, participants completed a repeated-sprint ability (RSA) test on a rowing ergometer (8 × 25-s "all-out" repetitions interspersed with 25 s of passive recovery). Power output (PO), oxygen uptake, perceptual-motor capacity (turning off a traffic light with a predetermined code), cerebral (Δ[Hbdiff]) and muscle (Δ[Hb/Mb]diff) oxygenation, cerebral total haemoglobin concentration (Δ[THb]) and muscle total haemoglobin/myoglobin concentration (Δ[THb/Mb]) were measured during each RSA repetition and/or recovery period. Results: From Pre-to Post-1 and Post-2, maximal PO, mean PO (MPO) of the first half of the test (repetitions 1–4), oxygen uptake, end-repetition cerebral Δ[Hbdiff] and Δ[THb], end-repetition muscle Δ[Hb/Mb]diff and Δ[THb/Mb] and perceptual-motor capacity remained unchanged in both groups. Conversely, MPO of the second half of the test (repetitions 5–8) was higher at Post-1 than at Pre-in RSH-VHL only (p < 0.01), resulting in a lower percentage decrement score over the entire RSA test (20.4% ± 6.5% vs. 23.9% ± 7.0%, p = 0.01). Furthermore, MPO (5–8) was greater in RSH-VHL than in RSN at Post-1 (p = 0.04). These performance results were accompanied by an increase in muscle Δ[THb/Mb] (p < 0.01) and a concomitant decrease in cerebral Δ[THb] (p < 0.01) during the recovery periods of the RSA test at Post-1 in RSH-VHL. Conclusion: Four weeks of RSH-VHL including maximal EEBH improved the ability of elite judo athletes to repeat high-intensity efforts. The performance improvement, observed 5 days but not 12 days after training, may be due to enhanced muscle perfusion. The unchanged oxygen uptake and the decrease in cerebral regional blood volume observed at the same time suggest that a blood volume redistribution occurred after the RSH-VHL intervention to meet the increase in muscle perfusion. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical utility of small airway function indices for early identification of GOLD stage 0 chronic obstructive pulmonary disease (COPD). Methods: This retrospective study enrolled 137 participants at our institution between January 2017 and December 2018, comprising 40 healthy controls, 46 individuals with GOLD stage 0 COPD, and 51 patients with established COPD. Pulmonary function was assessed using the PowerCube spirometry system (GANSHORN, Germany). Parameters evaluated included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and small airway function indicators. Results: The COPD cohort exhibited significantly lower values across all lung function measures compared to the other two groups, particularly for dynamic lung volume parameters such as FEV1%predicted and FEV1/FVC%. Small airway function indices, including FEV3%predicted, FEF75%predicted, FEF50%predicted, FEF25%predicted, and MMEF%predicted, were markedly decreased in the COPD group (all p-values <0.001). Receiver operating characteristic (ROC) curve analysis demonstrated that MMEF/FVC% and FEV3/FVC% had high diagnostic accuracy for COPD, with MMEF/FVC% exhibiting the optimal sensitivity and specificity. Conclusion: Small airway function indices, especially MMEF/FVC%, can serve as effective tools for early identification of GOLD stage 0 COPD. Incorporation of these findings into clinical practice may facilitate early diagnosis and intervention, thereby improving treatment outcomes and patient quality of life. [ABSTRACT FROM AUTHOR]

Rationale: Clinical trials show that lumacaftor/ivacaftor (LUM/IVA) treatment has the potential to modify early cystic fibrosis (CF) disease progression in children as young as 2 years of age. Objectives: To assess the long-term impact of LUM/IVA treatment on CF disease progression in children aged 2–5 years. Methods: This phase 2 trial had two parts: part 1, a 48-week, randomized, double-blind, placebo-controlled study of LUM/IVA in children aged 2–5 years (previously reported) was followed by a 48-week open-label treatment period in which all children received LUM/IVA (part 2; reported here). Endpoints assessed in part 2 included absolute changes from baseline in chest magnetic resonance imaging (MRI) global score at Week 96; weight-for-age, stature-for-age, and body mass index (BMI)-for-age z-scores at Week 96; lung clearance index based on lung volume turnover required to reach 2.5% of starting N2 concentration (LCI2.5) through Week 96; chest MRI morphological score, chest MRI perfusion score, weight, stature, BMI, and microbiology cultures (oropharyngeal swabs) at Week 96; sweat chloride, amount of immunoreactive trypsinogen, fecal elastase-1 concentration, and fecal calprotectin through Week 96; and number of pulmonary exacerbations, time to first pulmonary exacerbation, and number of CF-related hospitalizations. Results: Forty-nine children received one or more doses of LUM/IVA in the open-label period (33 in the LUM/IVA to LUM/IVA group and 16 in the placebo to LUM/IVA group), with a mean exposure of 47.1 (standard deviation [SD], 5.2) weeks. The mean absolute change in MRI global score (negative value indicates improvement) from baseline at Week 96 was −2.7 (SD, 7.0; 95% confidence interval [CI], −5.2 to −0.1) in the LUM/IVA to LUM/IVA group and −5.6 (SD, 6.9; 95% CI, −9.2 to −1.9) in the placebo to LUM/IVA group. Improvements in LCI2.5, sweat chloride concentration, and markers of pancreatic function and intestinal inflammation were also observed in both groups. Growth parameters remained stable in both groups. The majority of children had adverse events considered mild (38.8%) or moderate (40.8%). Two (4.1%) children discontinued LUM/IVA treatment because of adverse events (distal intestinal obstruction syndrome [n = 1] and alanine aminotransferase increase [n = 1]). Conclusions: These findings confirm the potential for early LUM/IVA treatment to alter the trajectory of CF disease progression, including CF lung disease, in children as young as 2 years of age. Clinical trial registered with (NCT03625466). [ABSTRACT FROM AUTHOR]

This study analyzed Chest CT exams from 592 patients with SARS-CoV-2 between 2020 and 2022 using the open-source 3D Slicer software. We conducted lung segmentation and volume quantification to investigate inflated lung volume and different impairments volumes (inflammatory process and fibrosis, ground-glass opacities and the total affected lung) against SARS-CoV-2 variants (original strain, gamma, delta and omicron) during a mass vaccination campaign carried out in Botucatu/SP-Brazil (before, during, and after three doses). We aimed to verify whether these parameters (variants and vaccination) affected lung impairments. Our findings indicated that gamma variant was more detrimental than delta and omicron variants, with higher volumes in inflammatory process and fibrosis (13.78% against 9.00% and 8.90%), ground-glass opacity (31.73% against 25.81% and 29.04%) and total affected volume (45.99% against 35.26% and 38.43%), while a lower volume was observed for inflated lung volume (50.04% against 58.19% and 57.50%). The results also revealed substantial differences in pulmonary impairments between the first and the third vaccination stages. We noticed a reduction in volumes of inflammatory process and fibrosis (14.51% to 9.19%), ground-glass opacity (33.67% to 26.77%) and the total affected volume (48.60% to 36.42%), while inflated lung volume increased (48.80% to 58.12%). The study brings novelty approach and findings that enhances the understanding of variant-specific impacts on pulmonary impairments and highlights the vaccine efficacy in reducing lung damage from SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Non-specific interstitial pneumonia (NSIP) is an interstitial lung disease that can result in end-stage fibrosis. We investigated the influence of body composition and pulmonary fat attenuation volume (CTpfav) on overall survival (OS) in NSIP patients. Methods: In this retrospective single-center study, 71 NSIP patients with a median age of 65 years (interquartile range 21.5), 39 females (55%), who had a computed tomography from August 2009 to February 2018, were included, of whom 38 (54%) died during follow-up. Body composition analysis was performed using an open-source nnU-Net-based framework. Features were combined into: Sarcopenia (muscle/bone); Fat (total adipose tissue/bone); Myosteatosis (inter-/intra-muscular adipose tissue/total adipose tissue); Mediastinal (mediastinal adipose tissue/bone); and Pulmonary fat index (CTpfav/lung volume). Kaplan–Meier analysis with a log-rank test and multivariate Cox regression were used for survival analyses. Results: Patients with a higher (> median) Sarcopenia and lower (< median) Mediastinal Fat index had a significantly better survival probability (2-year survival rate: 83% versus 71% for high versus low Sarcopenia index, p = 0.023; 83% versus 72% for low versus high Mediastinal fat index, p = 0.006). In univariate analysis, individuals with a higher Pulmonary fat index exhibited significantly worse survival probability (2-year survival rate: 61% versus 94% for high versus low, p = 0.003). Additionally, it was an independent risk predictor for death (hazard ratio 2.37, 95% confidence interval 1.03–5.48, p = 0.043). Conclusion: Fully automated body composition analysis offers interesting perspectives in patients with NSIP. Pulmonary fat index was an independent predictor of OS. Relevance statement: The Pulmonary fat index is an independent predictor of OS in patients with NSIP and demonstrates the potential of fully automated, deep-learning-driven body composition analysis as a biomarker for prognosis estimation. Key Points: This is the first study assessing the potential of CT-based body composition analysis in patients with non-specific interstitial pneumonia (NSIP). A single-center analysis of 71 patients with board-certified diagnosis of NSIP is presented Indices related to muscle, mediastinal fat, and pulmonary fat attenuation volume were significantly associated with survival at univariate analysis. CT pulmonary fat attenuation volume, normalized by lung volume, resulted as an independent predictor for death. [ABSTRACT FROM AUTHOR]

Physiologically Based Pharmacokinetic (PBPK) models can provide forecasts of the drug residues within the organism. Ractopamine (RAC) is a typical β-agonist. In this study, we developed a PBPK model for RAC in goats. The goal was to predict the distribution of the drug after multiple oral administrations. The preliminary PBPK model for RAC in goats performed well in predicting the drug's distribution in most tissues. In our sensitivity analysis, we found that the parameter of Qclu (Blood Flow Volume through Lungs) had the greatest impact on the RAC concentrations in plasma, liver, and kidney and was the most sensitive parameter. Furthermore, our study aimed to assess the withdrawal time (WT) of RAC in different tissues after RAC long-term exposure in goats. We found that the WT of RAC in the kidney was the longest, lasting for 13 days. Overall, the insights gained from this study have important implications for optimizing drug administration in goats and ensuring appropriate withdrawal times to prevent any potential risks. [ABSTRACT FROM AUTHOR]

Background Objectives Method Results Conclusions When re‐learning a motor skill, practicing a variety of treatment targets promotes error processing and the exploration of motor control strategies, which initially disrupts accuracy during training (motor performance), but ultimately enhances generalization, retention, and transfer (motor learning). Cough skill training (CST) is feasible and efficacious to improve cough strength; however, previous studies have used the same practice target during training.Our goal was to examine the impact of CST with variable practice on motor performance, motor learning, and respiratory system adaptations.The study was a prospective three‐visit single group design. Twenty individuals with Parkinson's disease (PD) and concomitant dysphagia and dystussia completed two sessions of CST involving three randomized practice targets. Cough, lung volume, and airway clearance outcomes were assessed before and after treatment sessions with long‐term retention evaluated after 1 month.Peak expiratory flow rate improved after CST with variable practice for voluntary single (β = 0.35 L/s) and sequential (β = 0.22 L/s) cough, which were maintained after 1 month without treatment. The ability to expel material from the upper airway demonstrated a small magnitude of improvement (β = −1.87%). During CST, participants altered lung volume based on the treatment target and lung volume decreased during reflex cough after completing CST.Individuals with PD demonstrated improvements in several aspects of motor learning after two sessions of CST with variable practice. Increasing lung volume may not be an implicit strategy to upregulate voluntary cough strength in this treatment paradigm. The findings support the need for larger investigations exploring the potential benefits of this CST approach. [ABSTRACT FROM AUTHOR]

Endoscopic lung volume reduction (ELVR) using endobronchial valves (EBV) is a treatment option for a subset of patients with severe chronic obstructive pulmonary disease (COPD), suffering from emphysema and hyperinflation. In this pilot study, we aimed to determine the presence of bacterial biofilm infections on EBV and investigate their involvement in lack of clinical benefits, worsening symptomatology, and increased exacerbations that lead to the decision to remove EBVs. We analyzed ten COPD patients with ELVR who underwent EBV removal. Clinical data were compared to the microbiological findings from conventional EBV culture. In addition, EBV were analyzed by FISHseq, a combination of Fluorescence in situ hybridization (FISH) with PCR and sequencing, for visualization and identification of microorganisms and biofilms. All ten patients presented with clinical symptoms, including pneumonia and recurrent exacerbations. Microbiological cultures from EBV detected several microorganisms in all ten patients. FISHseq showed either mixed or monospecies colonization on the EBV, including oropharyngeal bacterial flora, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus spp., and Fusobacterium sp. On 5/10 EBV, FISHseq visualized biofilms, on 1/10 microbial microcolonies, on 3/10 single microorganisms, and on 1/10 no microorganisms. The results of the study demonstrate the presence of biofilms on EBV for the first time and its potential involvement in increased exacerbations and clinical worsening in patients with ELVR. However, further prospective studies are needed to evaluate the clinical relevance of biofilm formation on EBV and appropriate treatment options to avoid infections in patients with ELVR. [ABSTRACT FROM AUTHOR]

Background: The 6-minute walk test is a common clinical instrument for assessing patient's functional capacity. The 6MWT should be performed preferably indoors, on a flat, straight, hard surfaced corridor usually at least 30 meter long. The test is also used for assessing the effect of therapies such as pulmonary rehabilitation, oxygen therapy, long‐term use of inhaled corticosteroids, and lung volume reduction surgery. The 6MWD in healthy adults has been reported to range from 400 to 700 metres. Method: A total of 300 subjects were included in the study. All the healthy volunteers presenting during the study period were included in the study, provided they met the inclusion and exclusion criteria as above. A written informed consent was taken from all the subjects who were to be included in the study. They were assured about the maintenance of confidentiality and the nature of voluntary participation. Once consent was given, they were included in the study. Result: In the present study, there were 150 males and 150 females. They were comparable in terms of age. The height and weight of males was more than females. It can be concluded from the present study that there is an increase in the hemodynamic parameters immediately after the test. However, the levels return to normal/baseline when measured 4 minutes after the test. Conclusion: The prediction equation developed from distance walked is: 6MWD (females) = 83.76 – (1.42*Age in years) – (3.98*Weight in kgs)+ (426.60*Height in metres). 6MWD (males) = 553.46 – (2.62*Age in years) + (1.82*Weight in kgs) - (38.98*Height in metres. [ABSTRACT FROM AUTHOR]

Bronchoscopic lung volume reduction (BLVR) is an established treatment modality for the management of advanced chronic obstructive pulmonary disease complicated by severe emphysema and hyperinflation refractory to other therapies. BLVR aims to reduce hyperinflation and residual volume, thereby improving pulmonary function, symptom control, and quality of life. Multiple distinct devices and technologies, including endobronchial coils, thermal vapor ablation, bio-lung volume reduction, and airway bypass stenting, have been developed to achieve lung volume reduction with varying degrees of accessibility and evidence. The most promising BLVR treatment modality to date has been the placement of one-way endobronchial valves (EBVs), with more than 25,000 cases performed worldwide. Identifying symptomatic patients who would benefit from BLVR is challenging and can be time and resource intensive, and candidacy may be limited by physiologic parameters. Additional new technologies may be able to improve the identification and evaluation of candidates as well as increase the portion of evaluated patients who ultimately qualify for BLVR. In this review, we aim to provide historical context to BLVR, summarize the available evidence regarding its use, discuss potential complications, and provide readers with a clear guide to patient selection and referral for BLVR, with a focus on EBV placement. In addition, we will highlight potential future directions for the field. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is an incurable, progressive respiratory disease that may have a significant negative impact on the morbidity and mortality of affected patients. A substantial portion of the world's population is affected by COPD, and despite optimal medical management with medications, supplemental oxygen, and pulmonary rehabilitation, many patients are left debilitated because of this disease. Bronchoscopic treatment modalities offer a less-invasive method for the treatment of refractory COPD compared to surgical interventions and have expanded the potential therapeutic options for these patients. Bronchoscopic lung volume reduction is aimed at decreasing the hyperinflation and air trapping that occur in emphysema, and the most studied and successful intervention is endobronchial valve placement. Endobronchial coils, polymeric sealants, and thermal ablation are other researched alternatives. Additional interventional procedures are being investigated for the treatment of the mucus hypersecretion and cough that are associated with the chronic bronchitis phenotype of COPD and include targeted lung denervation, metered dose spray cryotherapy, deobstruction balloon, and bronchial rheoplasty. This review summarizes the most recent evidence pertaining to available therapies for the management of COPD, including chronic bronchitis, with a particular focus on bronchoscopic interventions. [ABSTRACT FROM AUTHOR]

OBJECTIVES Endoscopic evaluation of anastomosis is effective for the early detection of anastomotic complications after a bronchoplastic procedure. Herein, we aimed to clarify important findings for predicting anastomotic complications. METHODS This single-centre retrospective study included patients who underwent bronchoplastic surgery between April 2013 and September 2023. Only cases in which bronchoscopy was performed both 1 and 2 weeks after surgery were included. Endoscopic findings (classification by Ludwig and Stoelben, mucosa colour, oedema, slough area and colour and depression) were reviewed for all cases. The accuracy of these findings for predicting anastomotic complications was evaluated. RESULTS Of the 190 patients included in this study, 14 (7.4%) experienced anastomotic abnormalities, 11 had fistulas (5.8%) and 7 had stenosis (3.7%). The onsets of fistula and stenosis were 20–28 and 20–44 days after surgery, respectively. In 102 patients (53.7%), the slough worsened from the first to the second week postsurgery. Therefore, it was easier to evaluate slough 2 weeks postsurgery rather than 1-week postsurgery. The positive/negative predicted values of anastomotic complications in endoscopic findings 2 weeks postsurgery were circular slough, 34.2%/99.3%; slough with dark colour, 39.3%/98.1%; and depression, 54.2%/99.4%. The incidence of anastomotic abnormalities was 0% in cases without the 3 findings, 10% in cases with at least 1 finding and 67% in cases with all 3 findings. CONCLUSIONS The endoscopic findings of slough on the anastomosis 2 weeks after bronchoplasty can be easily evaluated and accurately predict complications. Three important endoscopic findings were circular slough, dark colour and depression. [ABSTRACT FROM AUTHOR]

Emphysema in patients with chronic obstructive pulmonary disease (COPD) is characterized by progressive inflammation. Preclinical studies suggest that lung volume reduction surgery (LVRS) and mesenchymal stromal cell (MSC) treatment dampen inflammation. We investigated the effects of bone marrow-derived MSC (BM-MSC) and LVRS on circulating and pulmonary immune cell profiles in emphysema patients using mass cytometry. Blood and resected lung tissue were collected at the first LVRS (L1). Following 6–10 weeks of recovery, patients received a placebo or intravenous administration of 2 × 106 cells/kg bodyweight BM-MSC (n = 5 and n = 9, resp.) in week 3 and 4 before the second LVRS (L2), where blood and lung tissue were collected. Irrespective of BM-MSC or placebo treatment, proportions of circulating lymphocytes including central memory CD4 regulatory, effector memory CD8 and γδ T cells were higher, whereas myeloid cell percentages were lower in L2 compared to L1. In resected lung tissue, proportions of Treg (p = 0.0067) and anti-inflammatory CD163− macrophages (p = 0.0001) were increased in L2 compared to L1, while proportions of pro-inflammatory CD163+ macrophages were decreased (p = 0.0004). There were no effects of BM-MSC treatment on immune profiles in emphysema patients. However, we observed alterations in the circulating and pulmonary immune cells upon LVRS, suggesting the induction of anti-inflammatory responses potentially needed for repair processes. [ABSTRACT FROM AUTHOR]

Background The possibility of coil dislocation in computed tomography (CT)-guided microcoil localization of superficial pulmonary nodules is relatively high. The aim of the study is to investigate the outcomes of deeper localization technique during CT-guided microcoil localization of superficial pulmonary nodules before video-assisted thoracoscopic surgery (VATS). Methods Fifty-seven identified superficial pulmonary nodules (nodule–pleural distance ≤ 1 cm on CT image) from 51 consecutive patients underwent CT-guided microcoil localization, and subsequent VATSs were included. The rate of technical success, complications, and excised lung volume were compared between deeper localization technique group and conventional localization technique group. Results The technical success rate of the localization procedure was 100% (25/25) in the deeper localization group and 81.3% (26/32) in the conventional localization group (p = 0.030). Excluding one case of lobectomy, the excised lung volume in the deeper localization group and the conventional localization group was 39.3 ± 23.5 and 37.2 ± 16.2 cm3 , respectively (p = 0.684). The incidence of pneumothorax was similar between the deeper localization group and the conventional localization group (24.0 vs. 21.9%, respectively, p = 0.850). The incidence of intrapulmonary hemorrhage in the deeper localization group was higher (16.0%) than that in the conventional localization group (6.3%), but the difference was not statistically significant (p = 0.388). Conclusion CT-guided microcoil localization of superficial pulmonary nodules prior to VATS using a deeper localization technique is feasible. Deeper localization technique reduced the occurrence of dislocation but did not increase excised lung volume. [ABSTRACT FROM AUTHOR]

Purpose: Air trapping, often attested in humans by elevated residual volume (RV) and ratio of RV on total lung capacity (RV/TLC), is frequently observed in asthma. Confirming these alterations in experimental asthma would be important for translational purposes. Herein, lung volumes were investigated in a mouse model of pulmonary allergic inflammation. Methods: Eight- to 10-week-old male C57BL/6 and BALB/c mice were exposed once daily to intranasal house dust mite (HDM) for 10 consecutive days. All readouts were measured 24 h after the last exposure. Lung volumes were assessed with the flexiVent using a new automated method consisting of degassing the lungs followed by a full-range pressure–volume maneuver. The weight and the volume of the lungs were also measured ex vivo and a lobe was further processed for histological analyses. Results: HDM exposure led to tissue infiltration with inflammatory cells, goblet cell hyperplasia, thickening of the airway epithelium, and elevated ex vivo lung weight and volume. It also decreased TLC and vital capacity but without affecting RV and RV/TLC. These observations were similar between the two mouse strains. Conclusion: Alterations of lung volumes in a murine model of pulmonary allergic inflammation are inconsistent with observations made in human asthma. These discrepancies reflect the different means whereby lung volumes are measured between species. The invasive method used herein enables RV to be measured more precisely and without the confounding effect of air trapping, suggesting that changes in RV and RV/TLC using this method in mice should be interpreted differently than in humans. [ABSTRACT FROM AUTHOR]

Only a subset of patients with severe emphysema qualify for lung volume reduction surgery or endobronchial valves. We previously demonstrated that stereotactic ablative radiation therapy of lung tumors reduces lung volume in treated lobes by creating localized lung fibrosis. We aimed to determine the safety and secondarily explore the efficacy of stereotactic irradiation for lung volume reduction (SILVR) over 18 months after intervention in patients with severe emphysema. We conducted a single-arm, prospective clinical trial in eligible patients with severe emphysema treated with unilateral stereotactic ablative radiation therapy (45 Gy in 3 fractions) to a target within the most emphysematous region. The primary outcome was safety in terms of incidence of grade ≥3 adverse events, and the secondary outcome was efficacy. Eight patients received the intervention. Median (range) baseline characteristics were age 73 years (63-78); forced expiratory volume in 1 second percent of predicted value (FEV 1 %) 28.5% (19.0-42.0); diffusing capacity of the lungs for carbon monoxide percent of predicted value 40% (24.0-67.0); and body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index 5.5 (5-9). The incidence of grade ≥3 adverse events was 3 of 8 (37.5%). The relative change in target lobe volume was –23.1% (–1.6 to –41.5) and –26.5% (–20.6 to –40.8) at 6 and 18 months, respectively. The absolute ΔFEV 1 % was greater in patients with a BODE index ≤5 versus ≥6 (+12.0% vs –2.0%). The mean baseline lung density (in Hounsfield units, reflecting the amount of preserved parenchyma) within the intermediate dose volume (V 60BED3) correlated with the absolute change in target lobe volume at 18 months. SILVR appears to be safe, with a signal for efficacy as a novel therapeutic alternative for patients with severe emphysema. SILVR may be most safe and effective in patients with a lower BODE index and/or less parenchymal destruction. [ABSTRACT FROM AUTHOR]

The right middle lobe often poorly expands after right upper lobectomy. Postoperative pulmonary function may be inferior after right upper lobectomy than after right lower lobectomy due to poor expansion of the middle lobe. This study examined the difference in the postoperative right middle lobe expansion and pulmonary function between right upper and right lower lobectomy. Patients who underwent right upper or right lower lobectomy through video-assisted thoracic surgery (n = 82) were enrolled in this retrospective study. Pulmonary function tests and computed tomography were performed preoperatively and at 1 year postoperatively. Using three-dimensional computed tomography volumetry, the preoperative and postoperative lung volumes were measured, and the predicted postoperative forced expiratory volume in 1 s was calculated. Middle lobe volume ratio (i.e., ratio of the postoperative to the preoperative middle lobe volume) and the postoperative forced expiratory volume in 1 s ratio (i.e., ratio of the measured to the predicted postoperative forced expiratory volume in 1 s) were compared between right upper and right lower lobectomy. Compared with the patients who underwent right upper lobectomy (n = 50), those who underwent right lower lobectomy (n = 32) had significantly higher middle lobe volume ratio (1.15 ± 0.32 vs. 1.63 ± 0.52, p < 0.001) and postoperative forced expiratory volume in 1 s ratio (1.12 ± 0.12 vs. 1.19 ± 0.13, p = 0.010). The right middle lobe showed more expansion and better recovery of postoperative pulmonary function after right lower lobectomy than after right upper lobectomy. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the dependence of Xe‐MRI gas transfer metrics upon age, sex, and lung volume in a group of healthy volunteers. Methods: Sixty‐five subjects with no history of chronic lung disease were assessed with 129Xe‐MRI using a four‐echo 3D radial spectroscopic imaging sequence and a dose of xenon titrated according to subject height that was inhaled from a lung volume of functional residual capacity (FRC). Imaging was repeated in 34 subjects at total lung capacity (TLC). Regional maps of the fractions of dissolved xenon in red blood cells (RBC), membrane (M), and airspace (Gas) were acquired at an isotropic resolution of 2 cm, from which global averages of the ratios RBC:M, RBC:Gas, and M:Gas were computed. Results: Data from 26 males and 36 females with a median age of 43 y (range: 20–69 y) were of sufficient quality to analyze. Age (p = 0.0006) and sex (p < 0.0001) were significant predictors for RBC:M, and a linear regression showed higher values and steeper decline in males: RBC:M(Males) = −0.00362 × Age + 0.60 (p = 0.01, R2 = 0.25); RBC:M(Females) = −0.00170 × Age + 0.44 (p = 0.02, R2 = 0.15). Similarly, age and sex were significant predictors for RBC:Gas but not for M:Gas. RBC:M, M:Gas and RBC:Gas were significantly lower at TLC than at FRC (plus inhaled volume), with an average 9%, 30% and 35% decrease, respectively. Conclusion: Expected age and sex dependence of pulmonary function concurs with 129Xe RBC:M imaging results, demonstrating that these variables must be considered when reporting Xe‐MRI metrics. Xenon doses and breathing maneuvers should be controlled due to the strong dependence of Xe‐MRI metrics upon lung volume. [ABSTRACT FROM AUTHOR]

Introduction: COPD is a leading cause of global mortality, particularly under-recognized and under-diagnosed. In 2020, it was the sixth leading cause of death in the US and has contributed to 4.72% of all-cause mortality (ACM) according to the Global Burden of Disease Study 2017. Factors influencing COPD-related mortality include smoking, aging populations, comorbidities, sarcopenia, physical capacity, and lack of effective treatments. Areas Covered: This review discusses various factors influencing COPD-related mortality and analyzes observational studies and pivotal RCTs evaluating the impact of different therapies on ACM. Expert Opinion: COPD significantly impacts ACM, necessitating effective management strategies. Smoking cessation is crucial in reducing mortality risk. Exacerbation management and comorbidity treatment are essential to improve patient outcomes. Various therapeutic interventions, such as smoking cessation, vaccination, long-term oxygen therapy, and lung volume reduction surgery, have shown benefits in reducing mortality. Pharmacotherapies might reduce the risk of mortality, although the current scientific evidences remain inconclusive. Advances in pharmacological interventions, tailored treatment plans, and physical activity programs are vital. More robust and long-term studies, focusing on real-world data and addressing biases in treatment allocation, are needed to conclusively determine the efficacy of different therapies in reducing ACM in COPD patients. [ABSTRACT FROM AUTHOR]

This article presents the findings of a study on bronchial remodeling in preschool children with severe preschool wheezing (SPW). The study identified two distinct classes of SPWs, BR1 and BR2, based on bronchial remodeling characteristics. These classes had different disease trajectories, clinical manifestations, and treatment responses. The study suggests that quantifying and targeting multiple bronchial remodeling features can help identify and monitor these two endotypes of SPWs. The article also emphasizes the need for biomarkers and genetic characteristics to easily identify these endotypes. [Extracted from the article]

Rationale: A U-shaped relationship should exist between lung volume and pulmonary vascular resistance (PVR), with minimal PVR at FRC. Thus, positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS) should increase PVR if it induces significant lung distension compared with recruitment. However, this has never been proved in patients. Objectives: To study the effects of PEEP on PVR according to lung recruitability, evaluated by the recruitment-to-inflation (R/I) ratio. Methods: In patients with ARDS, we measured hemodynamic (pulmonary artery catheter), echocardiographic, and ventilatory variables (including esophageal pressure) at both low PEEP and higher PEEP by 10 cm H2O. Preload responsiveness was assessed by the passive leg-raising test at high PEEP. Measurements and Main Results: We enrolled 23 patients, including 10 low recruiters (R/I <0.5) and 13 high recruiters (R/I ⩾0.5). Raising PEEP from 4 (2–5) to 14 (12–15) cm H2O increased PVR in low recruiters (from 160 [120–297] to 243 [166–380] dyn·s/cm5; P < 0.01), whereas PVR was unchanged in high recruiters (from 224 [185–289] to 235 [168–300] dyn·s/cm5; P = 0.55). Right-to-left ventricular end-diastolic area ratio simultaneously increased in low recruiters (from 0.54 [0.50–0.59] to 0.64 [0.56–0.70]; P < 0.01) while remaining stable in high recruiters (from 0.70 [0.65–0.79] to 0.68 [0.58–0.80]; P = 0.48). Raising PEEP decreased cardiac index only in preload responsive patients. Conclusions: PEEP increases PVR only when it induces significant lung distension compared with recruitment according to the R/I ratio. Tailoring PEEP on this recruitability index should mitigate its hemodynamic effects. [ABSTRACT FROM AUTHOR]

Purpose: We elucidated the effects of planned resection volume on postoperative pulmonary function and changes in residual lung volume during segmentectomy. Methods: This study included patients who underwent thoracoscopic segmentectomy between January 2017 and December 2022 and met eligibility criteria. Pre- and post-resection spirometry and computed tomography were performed. Three-dimensional reconstructions were performed by using computed tomography images to calculate the volumes of the resected, remaining, and nonoperative side regions. Based on the resected region volume, patients were divided into the higher and lower volume segmentectomy groups. Changes in lung volume and pulmonary function before and after the surgery were comparatively analyzed. Results: The median percentage of resected lung volume was 10.9%, forming the basis for categorizing patients into the two groups. Postoperative forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) ratios to preoperative measurements in both groups did not differ significantly (FEV1, p = 0.254; FVC, p = 0.777). Postoperative FEV1 and FVC ratios to their predicted postoperative values were significantly higher in the higher volume segmentectomy group than in the lower volume segmentectomy group (FEV1, p = 0003; FVC, p < 0.001). The higher volume segmentectomy group showed significantly greater post-to-preoperative lung volume ratio in overall, contralateral, ipsilateral, residual lobe and residual segment than the lower volume segmentectomy group. Conclusions: Postoperative respiratory function did not differ significantly between the higher- and lower-volume segmentectomy groups, indicating improved respiratory function because of substantial postoperative residual lung expansion. Our findings would aid in determining the extent of resection during segmentectomy. [ABSTRACT FROM AUTHOR]

Abstract Background Respiratory compromise among ankylosing spondylitis (AS) patients is characterized by restrictive pulmonary function, leading to the need for a meticulous assessment of lung volume. Compared with conventional pulmonary function tests (PFTs), CT-based lung volume measurements have superior accuracy and are crucial for understanding functional limitations in AS. This study investigated the correlation between CT lung volume and PFT parameters in AS patients, with a focus on changes in CT parameters and lung volume in patients with compromised pulmonary function. Methods A total of 79 AS patients were included, and their full-length radiographs, thoracic CT scans, and PFT data were analysed. Specialized software was used to estimate the total and lobar lung volumes from the CT scans. The relationship between lung volume and PFT results was examined, and a multiple linear regression model was constructed to determine the influence of radiographic and CT parameters on total lung volume (TLV). Patients were classified into normal or impaired pulmonary function groups based on PFT outcomes, thus facilitating comparative analyses of radiographic and CT parameters and lung volumes between these groups. Results Among the 79 AS patients, 19 had normal function, 4 had mixed dysfunction, and 56 experienced restrictive dysfunction. PFT parameters, including FVC, FEV1, TLC, FEV1%, and TLC%, showed varying correlations with TLV and individual lobe volume. Patients with compromised pulmonary function exhibited more pronounced spinal kyphosis and experienced a decline in TLV. Multiple regression analysis revealed that lung height and horizontal and vertical lung diameters independently influenced TLV. Notably, a decrease in lung height was observed in patients with impaired pulmonary function, whereas the horizontal and vertical diameters of the lungs remained stable. Conclusions In AS patients, TLV was found to be correlated with pulmonary function, particularly parameter such as FVC, FEV1, and TLC. A significant reduction in TLV was observed in those with impaired pulmonary function, with the primary contributing factor being a decrease in lung height.

Abstract Background Increasing functional residual capacity (FRC) or tidal volume (VT) reduces airway resistance and attenuates the response to bronchoconstrictor stimuli in animals and humans. What is unknown is which one of the above mechanisms is more effective in modulating airway caliber and whether their combination yields additive or synergistic effects. To address this question, we investigated the effects of increased FRC and increased VT in attenuating the bronchoconstriction induced by inhaled methacholine (MCh) in healthy humans. Methods Nineteen healthy volunteers were challenged with a single-dose of MCh and forced oscillation was used to measure inspiratory resistance at 5 and 19 Hz (R5 and R19), their difference (R5-19), and reactance at 5 Hz (X5) during spontaneous breathing and during imposed breathing patterns with increased FRC, or VT, or both. Importantly, in our experimental design we held the product of VT and breathing frequency (BF), i.e, minute ventilation (VE) fixed so as to better isolate the effects of changes in VT alone. Results Tripling VT from baseline FRC significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Doubling VT while halving BF had insignificant effects. Increasing FRC by either one or two VT significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Increasing both VT and FRC had additive effects on R5, R19, R5-19 and X5, but the effect of increasing FRC was more consistent than increasing VT thus suggesting larger bronchodilation. When compared at iso-volume, there were no differences among breathing patterns with the exception of when VT was three times larger than during spontaneous breathing. Conclusions These data show that increasing FRC and VT can attenuate induced bronchoconstriction in healthy humans by additive effects that are mainly related to an increase of mean operational lung volume. We suggest that static stretching as with increasing FRC is more effective than tidal stretching at constant VE, possibly through a combination of effects on airway geometry and airway smooth muscle dynamics.

Background. The effect of spinal deformity surgical correction in children with severe neuromuscular scoliosis (NMS) on lung function remains unexplored.Objective. The aim of the study is to — to survey the dynamics of volume and structure of lungs pneumatization in children after surgical correction of severe neuromuscular deformities of the spine complicated by respiratory disorders.Methods. CT scans of lungs from 5 children with right-sided NMS, grade IV (Cobb angle < 50°) and functional respiratory disorders (lung capacity < 30% of normal value according to spirometry data and/or clinical signs of respiratory failure) were retrospectively studied. Right and left lungs volumes, their ratio (asymmetry index), indicators of distribution of tissue density of each lung (as a percentage of total volume) before (not earlier than 2 months) and after (not later than 3 months) surgical correction of scoliosis were determined via the data processing from CT scans of the thoracic spine.Results. All children had both lung volumes below reference values (healthy peers) before surgery. The right lung volume increased by 11% (6.4–40.6%), the left lung — by 41% (22.5–90%) with the asymmetry index approaching the reference values for the corresponding age after correction of spinal deformity (the value of scoliotic deformity decreased (median) from 94 to 68°). The volume of normal ventilation zones increased from 30 to 50% on the right side, and from 41 to 55% on the left side, primarily due to decrease in the volume of hypoventilation zones, but not atelectasis and emphysema.Conclusion. Surgical correction of spinal deformity in children with NMS, grade IV, complicated with respiratory failure led to normalization of lungs volume and tissue density characteristics already in the early postoperative period.

Abstract Purpose The present study aimed to investigate the clinical characteristics and lung function impairment in young people diagnosed with chronic obstructive pulmonary disease (COPD). Patients and methods We retrospectively enrolled patients with COPD who underwent symptom assessment and comprehensive pulmonary function tests at the First Affiliated Hospital of Guangzhou Medical University between August 2017 and March 2022. The patients were categorized into two groups based on age: a young COPD group (aged 20–50 years) and an old COPD group (aged > 50 years). Results A total of 1282 patients with COPD were included in the study, with 76 young COPD patients and 1206 old COPD patients. Young COPD patients exhibited a higher likelihood of being asymptomatic, lower rates of smoking, and a lower smoking index compared to old COPD patients. Although young COPD patients had higher median post-bronchodilator forced expiratory volume in 1 s (post-BD FEV1) (1.4 vs.1.2 L, P = 0.019), diffusing capacity of the lung for carbon monoxide (DLCO) (7.2 vs. 4.6, P 120%) between two groups. Surprisingly, the prevalence of reduced DLCO was found to be 71.1% in young COPD, although lower than in old COPD (85.2%). Conclusion Young COPD showed fewer respiratory symptoms, yet displayed a similar severity distribution by GOLD categories. Furthermore, a majority of them demonstrated lung hyperinflation and reduced DLCO. These results underscore the importance of a comprehensive assessment of lung function in young COPD patients.

Identifying biomarkers in fibrotic lung disease is key for early anti-fibrotic intervention. Dynamic contrast-enhanced (DCE) MRI offers valuable perfusion-related insights in fibrosis but adapting human MRI methods to rodents poses challenges. Here, we explored these translational challenges for the inflammatory and fibrotic phase of a bleomycin lung injury model in rats. Eleven male Sprague-Dawley rats received a single intratracheal dose of bleomycin (1000iU), four control rats received saline. Imaging was performed on days 7 and 28 post-induction. Ultra-short echo time imaging was used to image the lung for 7 minutes after which Clariscan was injected intravenously. Lung signal changes were measured for an additional 21 minutes. Images were reconstructed with a sliding-window approach, providing a temporal resolution of 10 seconds per image. After imaging on day 28, animals were euthanized, and lungs were collected for histology. Bleomycin-exposed rats initially exhibited reduced body weight, recovering to control levels after 20 days. Lung volume increased in bleomycin animals from 4.4±0.9 ml in controls to 5.5±0.5 ml and 6.5±1.2 ml on day 7 and 28. DCE-MRI showed no change of initial gradient of relative enhancement in the curves between controls and bleomycin animals on day 7 and 28 post-induction. On day 7, the DCE-MRI washout phase in bleomycin animals had higher signals than the saline group and than observed at a later time point. Lung pixels were binned in 7 enhancement classes. On day 28, the size of low relative enhancement bins almost doubled in volume compared to controls and animals on day 7 post-induction. Histology on day 28 suggests that findings could be explained by changes in lung tissue density due to lung volume increase. Adapting this clinical MRI method to rodents at 9.4T remains a challenge. Future studies may benefit from lower field strength MRI combined with higher temporal resolution DCE-MRI. [ABSTRACT FROM AUTHOR]

Introduction: Currently, there is a lack of bronchoscopic lung volume reduction options that do not depend on fissure integrity. Endobronchial coils have been extensively studied to address this need but exhibited variable patient response and have been discontinued. Lung tension device (LTD) coils represent the next-generation coil treatment. This study aimed to evaluate safety, feasibility, and efficacy of LTD-coil treatment. Methods: Patients with advanced emphysema and hyperinflation were enrolled at two European sites. LTD-coils (Free Flow Medical, Fremont, CA, USA) were implanted in the two most destructed lobes, as determined by quantitative CT analysis, in two separate procedures. The primary endpoint was 3-month follow-up after the last treatment. Results: Fourteen patients (50% male, median age 64 years, FEV1 23%predicted, RV 249%predicted) received LTD-coil treatment: 12 received bilateral and 2 unilateral treatment. Six serious respiratory adverse events occurred within the initial 3 months posttreatment, including one device-associated death. Treatment significantly reduced in- and expiratory volume of the treated lobes (−410 [−710, −340], p = 0.004 and −650 [−730, −190] mL, p < 0.001, respectively) and improved quality of life (SGRQ total score −4.6 [−21.0, −2.6], p < 0.001). However, at a group level, no significant improvements in pulmonary function or 6-min walk distance were observed. Responder rates ranged from 18% to 54% for the different endpoints. Conclusion: This first-in-human study shows that the new LTD-coil procedure is feasible with a safety profile comparable to the previous coil treatment. While the treatment effectively reduced lobar volume and modestly improved quality of life up to 3 months’ follow-up, at a group level it did not significantly enhance pulmonary function or exercise capacity. [ABSTRACT FROM AUTHOR]

A cardiopulmonary exercise test (CPET) is a test assessing an individual's physiological response during exercise. Results may be affected by body composition, which is best evaluated through imaging techniques like magnetic resonance imaging (MRI). The aim of this study was to assess relationships between body composition and indices obtained from CPET. A total of 234 participants (112 female), all aged 50 years, underwent CPETs and whole-body MRI scans (> 1 million voxels). Voxel-wise statistical analysis of tissue volume and fat content was carried out with a method called Imiomics and related to the CPET indices peak oxygen consumption (V̇O2peak), V̇O2peak scaled by body weight (V̇O2kg) and by total lean mass (V̇O2lean), ventilatory efficiency (V̇E/V̇CO2-slope), work efficiency (ΔV̇O2/ΔWR) and peak exercise respiratory exchange ratio (RERpeak). V̇O2peak showed the highest positive correlation with volume of skeletal muscle. V̇O2kg negatively correlated with tissue volume in subcutaneous fat, particularly gluteal fat. RERpeak negatively correlated with tissue volume in skeletal muscle, subcutaneous fat, visceral fat and liver. Some associations differed between sexes: in females ΔV̇O2/ΔWR correlated positively with tissue volume of subcutaneous fat and V̇E/V̇CO2-slope with tissue volume of visceral fat, and, in males, V̇O2peak correlated positively to lung volume. In conclusion, voxel-based Imiomics provided detailed insights into how CPET indices were related to the tissue volume and fat content of different body structures. [ABSTRACT FROM AUTHOR]

Background: Understanding the characteristics of pulmonary resistance and elastance in relation to the location of airway narrowing, e.g., tracheal stenosis vs. intrapulmonary airway obstruction, will help us understand lung function characteristics and mechanisms related to different airway diseases. Methods: In this study, we used ex vivo sheep lungs as a model to measure lung resistance and elastance across a range of transpulmonary pressures (5–30 cmH2O) and ventilation frequencies (0.125–2 Hz). We established two tracheal stenosis models by inserting plastic tubes into the tracheas, representing mild (71.8% lumen area reduction) and severe (92.1%) obstructions. For intrapulmonary airway obstruction, we induced airway narrowing by challenging the lung with acetylcholine (ACh). Results: We found a pattern change in the lung resistance and apparent lung elastance as functions of ventilation frequency that depended on the transpulmonary pressure (or lung volume). At a transpulmonary pressure of 10 cmH2O, lung resistance increased with ventilation frequency in severe tracheal stenosis, whereas in ACh-induced airway narrowing the opposite occurred. Furthermore, apparent lung elastance at 10 cmH2O decreased with increasing ventilation frequency in severe tracheal stenosis whereas in ACh-induced airway narrowing the opposite occurred. Flow-volume analysis revealed that the flow amplitude was much sensitive to ventilation frequency in tracheal stenosis than it was in ACh induced airway constriction. Conclusions: Results from this study suggest that lung resistance and apparent elastance measured at 10 cmH2O over the frequency range of 0.125-2 Hz can differentiate tracheal stenosis vs. intrapulmonary airway narrowing in ex vivo sheep lungs. [ABSTRACT FROM AUTHOR]

Introduction: In post-COVID survivors, transforming growth factor-beta-1 (TGF-b1) might mediate fibroblast activation, resulting in persistent fibrosis. Methods: In this study, 82 survivors of COVID-19-associated ARDS were examined at 6- and 24-months post-ICU discharge. At 6-months, quantitative CT analysis of lung attenuation was performed and active TGF-b1 was measured in blood and exhaled breath condensate (EBC). Results: At 6-months of ICU-discharge, patients with reduced DmCO/alveolar volume ratio exhibited higher plasma and EBC levels of active TGF-b1. Plasma TGF-b1 levels were elevated in dyspneic survivors and directly related to the high-attenuation lung volume. In vitro, plasma and EBC from survivors induced profibrotic changes in human primary fibroblasts in a TGF-b receptordependent manner. Finally, at 6-months, plasma and EBC active TGF-b1 levels discriminated patients who, 24-months post-ICU-discharge, developed gas exchange impairment. Discussion: TGF-b1 pathway plays a pivotal role in the early-phase fibrotic abnormalities in COVID-19-induced ARDS survivors, with significant implications for long-term functional impairment. [ABSTRACT FROM AUTHOR]

It is self‐evident that our chests expand and contract during breathing but, surprisingly, exactly how individual alveoli change shape over the respiratory cycle is still a matter of debate. Some argue that all the alveoli expand and contract rhythmically. Others claim that the lung volume change is due to groups of alveoli collapsing and reopening during ventilation. Although this question might seem to be an insignificant detail for healthy individuals, it might be a matter of life and death for patients with compromised lungs. Past analyses were based on static post‐mortem preparations primarily due to technological limitations, and therefore, by definition, incapable of providing dynamic information. In contrast, this study provides the first comprehensive dynamic data on how the shape of the alveoli changes, and, further, provides valuable insights into the optimal lung volume for efficient gas exchange. It is concluded that alveolar micro‐dynamics is nonlinear; and at medium lung volume, alveoli expand more than the ducts. [ABSTRACT FROM AUTHOR]

Introduction: Fetal magnetic resonance imaging (MRI) lung volume nomograms are increasingly used to prognosticate neonatal outcomes in fetuses with suspected pulmonary hypoplasia. However, pregnancies complicated by fetal anomalies associated with pulmonary hypoplasia may also be complicated by fetal growth restriction (FGR). If a small lung volume is suspected in such cases, it is often unclear whether the lungs are "small" because of underlying lung pathology, or small fetal size. Existing MRI lung volume nomograms have mostly been stratified by gestational age (GA), rather than estimated fetal weight (EFW). Therefore, we aimed to develop a novel fetal lung volume nomogram stratified by EFW. Methods: Consecutive fetal MRIs performed at a quaternary medical center from 2019 to 2021 were analyzed. MRIs performed due to fetal lung anomalies and cases with FGR were excluded. All MRIs were performed without IV contrast on GE 3 or 1.5 Tesla scanners (GE Healthcare). Images were reviewed by three experienced fetal radiologists. Freehand ROI in square centimeter was drawn around the contours of the lungs on consecutive slices from the apex to the base. The volume of the right, left and total lungs were calculated in mL. Lung volumes were plotted by both EFW and GA. Results: Among 301 MRI studies performed during the study period, 170 cases met inclusion criteria and were analyzed. MRIs were performed between 19- and 38-week gestation, and a sonographic EFW was obtained within a mean of 2.9 days (SD ± 5.5 days, range 0–14 days) of each MRI. Nomograms stratified by both EFW and GA were created using 200 g. and weekly intervals respectively. A formula using EFW to predict total lung volume was calculated: LV = 0.07497804 EFW0.88276 (R2 = 0.87). Conclusions: We developed a novel fetal lung volume nomogram stratified by EFW. If validated, this nomogram may assist clinicians predict outcomes in cases of fetal pulmonary hypoplasia with concomitant FGR. [ABSTRACT FROM AUTHOR]

Background: Despite the increasing use of non-invasive support modalities, many preterm infants still need invasive mechanical ventilation. Mechanical ventilation can lead to so-called ventilator-induced lung injury, which is considered an important risk factor in the development of bronchopulmonary dysplasia. Understanding the concepts of lung protective ventilation strategies is imperative to reduce the risk of BPD. Summary: Overdistension, atelectasis, and oxygen toxicity are the most important risk factors for VILI. A lung protective ventilation strategy should therefore optimize lung volume (resolve atelectasis), limit tidal volumes, and reduce oxygen exposure. Executing such a lung protective ventilation strategy requires basic knowledge on neonatal lung physiology. Studies have shown that volume-targeted ventilation (VTV) stabilizes tidal volume delivery, reduces VILI, and reduces BPD in preterm infants with respiratory distress syndrome. High-frequency ventilation (HFV) also reduces BPD although the effect is modest and inconsistent. It is unclear if these benefits also apply to infants with more heterogeneous lung disease. Key Messages: Understanding basic physiology and the concept of ventilator-induced lung injury is essential in neonatal mechanical ventilation. Current evidence suggests that the principles of lung protective ventilation are best captured by VTV and HFV. [ABSTRACT FROM AUTHOR]

The movement of air into and out of the lungs is facilitated by changes in pressure within the thoracic cavity relative to atmospheric pressure, as well as the resistance encountered by airways. In this process, the movement of air into and out of the lungs is driven by pressure gradients established by changes in lung volume and intra-alveolar pressure. However, pressure never sucks! The concept that pressure never sucks, pressure only pushes encapsulates a fundamental principle in the behavior of gases. This concept challenges common misconceptions about pressure, shedding light on the dynamic forces that govern the movement of gases. In this Illumination, we explore the essence of this concept and its applications in pulmonary ventilation. Pressure is one of the most important concepts in physics and physiology. Atmospheric pressure at sea level is equal to 1 atmosphere or around 101,325 Pascal [Pa (1 Pa = 1 N/m2)]. This huge pressure is pushing down on everything all the time. However, this pressure is difficult to understand because we do not often observe the power of this incredible force. We used five readily available, simple, and inexpensive demonstrations to introduce the physics and power of pressure. This extraordinarily complex physics concept was approached in a straightforward and inexpensive manner while still providing an understanding of the fundamental concepts. These simple demonstrations introduced basic concepts and addressed common misconceptions about pressure. NEW & NOTEWORTHY: The concept that pressure never sucks, pressure only pushes challenges common misconceptions about pressure, shedding light on the dynamic forces that govern the movement of gases. In this Illumination, we will explore the essence of this concept and its applications in pulmonary ventilation. Specifically, we used five readily available, simple, inexpensive demonstrations to introduce the physics and power of pressure. [ABSTRACT FROM AUTHOR]

Objective: Adverse respiratory outcomes in post-9/11 veterans with elevated urinary metal measures and enrolled in the VA's Toxic Embedded Fragment registrywere compared to thosewithout elevated urinary metals. Methods: Veterans completed questionnaires, underwent pulmonary physiology tests (pulmonary function and oscillometry), and provided urine samples for analysis of 13 metals. Respiratory symptoms, diagnoses, and physiology measures were compared in veterans with ≥1 urine metal elevation to those without metal elevations, adjusted for covariates, including smoking. Results: Among 402 study participants, 24% had elevated urinemetals, often just exceeding upper limits of reference values. Compared to veterans without elevated metals, those with elevated metals had had higher FEV1 values but similar frequencies of respiratory symptoms and diagnoses and abnormalities on pulmonary physiology tests. Conclusions: Mild systemic metal elevations in post-9/11 veterans are not associated with adverse respiratory health outcomes. [ABSTRACT FROM AUTHOR]

Objective: To assess and compare the value of antenatally determined observed‐to‐expected (O/E) lung‐area‐to‐head‐circumference ratio (LHR) on ultrasound examination vs O/E total fetal lung volume (TFLV) on magnetic resonance imaging (MRI) examination to predict postnatal survival of fetuses with isolated, expectantly managed left‐sided congenital diaphragmatic hernia (CDH). Methods: This was a multicenter retrospective study including all consecutive fetuses with isolated CDH that were managed expectantly in Mannheim, Germany, and in five other European centers, that underwent at least one ultrasound examination for measurement of O/E‐LHR and one MRI scan for measurement of O/E‐TFLV during pregnancy. All MRI data were centralized, and lung volumes were measured by two experienced operators blinded to the pre‐ and postnatal data. Multiple logistic regression analyses were performed to examine the effect on survival at hospital discharge of various perinatal variables, including the center of management. In left‐sided CDH with intrathoracic herniation of the liver, receiver‐operating‐characteristics (ROC) curves were constructed separately for cases from Mannheim and the other five European centers and were used to compare O/E‐TFLV and O/E‐LHR in the prediction of postnatal survival. Results: From Mannheim, 309 patients were included with a median gestational age (GA) at ultrasound examination of 29.6 (range, 19.7–39.1) weeks and median GA at MRI examination of 31.1 (range, 18.0–39.9) weeks. From the other five European centers, 116 patients were included with a median GA at ultrasound examination of 26.7 (range, 20.6–37.6) weeks and median GA at MRI examination of 27.7 (range, 21.3–37.9) weeks. Regression analysis demonstrated that the survival rates at discharge were lower in left‐sided CDH (odds ratio (OR), 0.349 (95% CI, 0.133–0.918), P = 0.033) and those with intrathoracic liver (OR, 0.297 (95% CI, 0.141–0.628), P = 0.001), and higher with increasing O/E‐TFLV (OR, 1.123 (95% CI, 1.079–1.170), P < 0.001), advanced GA at birth (OR, 1.294 (95% CI, 1.055–1.588), P = 0.013) and when birth occurred in Mannheim (OR, 7.560 (95% CI, 3.368–16.967), P < 0.001). Given the difference in survival rate between Mannheim and the five other European centers, ROC curve comparisons between the two imaging modalities were presented separately. For cases of left‐sided CDH with intrathoracic herniation of the liver, pairwise comparison showed no significant difference between the area under the ROC curves for the prediction of postnatal survival between O/E‐TFLV and O/E‐LHR in Mannheim (mean difference = 0.025, P = 0.610, standard error = 0.050), whereas there was a significant difference in the other European centers studied (mean difference = 0.056, P = 0.033, standard error = 0.056). Conclusions: In fetuses with left‐sided CDH and intrathoracic herniation of the liver, the predictive value for postnatal survival of O/E‐TFLV on MRI examination and O/E‐LHR on ultrasound examination was similar in one center (Mannheim), but O/E‐TFLV had better predictive value compared to O/E‐LHR in the five other European centers. Hence, in these five European centers, MRI should be included in the diagnostic process for left‐sided CDH. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Chronic lung allograft dysfunction (CLAD) is the leading long-term cause of poor outcomes after transplant and manifests by fibrotic remodeling of small airways and/or pleuroparenchymal fibroelastosis. This study evaluated the effect of pirfenidone on quantitative radiographic and pulmonary function assessment in patients with CLAD. We performed a single-center, 6-month, randomized, placebo-controlled trial of pirfenidone in patients with CLAD. Randomization was stratified by CLAD phenotype. The primary outcome for this study was change in radiographic assessment of small airways disease, quantified as percentage of lung volume using parametric response mapping analysis of computed tomography scans (PRMfSAD); secondary outcomes included change in forced expiratory volume in 1 second (FEV 1), change in forced vital capacity (FVC), and change in radiographic quantification of parenchymal disease (PRMPD). Linear mixed models were used to evaluate the treatment effect on outcome measures. The goal enrollment of 60 patients was not met due to the coronavirus disease of 2019 pandemic, with 23 patients included in the analysis. There was no significant difference over the study period between the pirfenidone vs placebo groups with regards to the observed change in PRMfSAD (+4.2% vs −0.4%; p = 0.22), FEV 1 (−3.5% vs −3.6%; p = 0.97), FVC (−1.9% vs −4.6%; p = 0.41), or PRMPD (−0.6% vs −2.5%; p = 0.30). The study treatment tolerance and adverse events were generally similar between the pirfenidone and placebo groups. Pirfenidone had no apparent impact on radiographic evidence of allograft dysfunction or pulmonary function decline in a single-center randomized trial of CLAD patients that did not meet enrollment goals but had an acceptable tolerance and side-effect profile. [ABSTRACT FROM AUTHOR]

To compare static compliance of the respiratory system (C stRS) and the ratio of partial pressure of end-tidal to arterial carbon dioxide (P e′ CO 2 /PaCO 2), in healthy dogs using two approaches for tidal volume (V T) selection during volume-controlled ventilation: body mass based and driving pressure (ΔPaw) guided. Randomized, nonblinded, crossover, clinical trial. A total of 19 client-owned dogs anesthetized for castration and ovariohysterectomy. After a stable 10 minute baseline, each dog was mechanically ventilated with a V T selection strategy, randomized to a constant V T of 15 mL kg–1 of actual body mass (V TBW) or ΔPaw-guided V T (V TΔP) of 7–8 cmH 2 O. Both strategies used an inspiratory time of 1 second, 20% end-inspiratory pause, 4 cmH 2 O positive end-expiratory pressure and fraction of inspired oxygen of 0.4. Respiratory frequency was adjusted to maintain P e′ CO 2 between 35 and 40 mmHg. Respiratory mechanics, arterial blood gases and P e′ CO 2 /PaCO 2 were assessed. Continuous variables are presented as mean ± SD or median (interquartile range; quartiles 1–3), depending on distribution, and compared with Wilcoxon signed-rank tests. The V T was significantly higher in dogs ventilated with V TΔP than with V TBW strategy (17.20 ± 4.04 versus 15.03 ± 0.60 mL kg–1, p = 0.036). C stRS was significantly higher with V TΔP than with V TBW strategy [2.47 (1.86–2.86) versus 2.25 (1.79–2.58) mL cmH 2 O−1 kg–1, p = 0.011]. There were no differences in P e′ CO 2 /PaCO 2 between V TΔP and V TBW strategies (0.94 ± 0.06 versus 0.92 ± 0.06, p = 0.094). No discernible difference in ΔPaw was noted between the strategies. While no apparent difference was observed in the P e′ CO 2 /PaCO 2 between the V T selection strategies employed, C stRS significantly increased during the V TΔP approach. A future trial should explore if V TΔP improves perioperative gas exchange and prevents lung damage. [ABSTRACT FROM AUTHOR]