Total Lung Research Articles

Predicting life-threatening hemoptysis in traumatic pulmonary parenchymal injury using computed tomography semi-automated lung volume quantification.

Chest computed tomography (CT) can diagnose and assess the severity of pulmonary contusions. However, in cases of severe lung contusion, the total lung volume ratio may not accurately predict severity. This study investigated the association between life-threatening hemoptysis and chest CT imaging data on arrival at the emergency department in patients with pulmonary contusions or lacerations due to blunt chest injury. The records of 277 patients with lung contusions or lacerations treated at a trauma center between 2018 and 2022 were retrospectively reviewed. The ratio of the local lung contusion volume to lobe volume in each lobe was calculated from chest CT images. The maximal ratio in the Hounsfield unit (HU) range was defined as the highest ratio value within the HU range among five lobes. The median patient age was 41 years, and 68.6% were male. Life-threatening hemoptysis occurred in 39 patients. The area under the receiver operating characteristic curve for the maximal ratio at -500 HU to 100 HU was 96.52%. The cutoff value was 45.49%. Multivariate analysis showed a high maximal chest CT ratio ≥ 45.49% at -500 HU to 100 HU (adjusted odds ratio [aOR]: 104.66, 95% confidence interval [CI]: 21.81-502.16, p < 0.001), hemopneumothorax (aOR: 5.18, 95% CI: 1.25-21.47, p = 0.023), and chest abbreviated injury scale (AIS, aOR: 5.58, 95% CI: 1.68-18.57, p = 0.005) were associated with life-threatening hemoptysis. Maximal chest CT ratios ≥ 45.49% at -500 HU to 100 HU, hemopneumothorax, and high chest AIS scores are associated with life-threatening hemoptysis in patients with blunt chest trauma. The present study provides an objective index derived from chest CT images to predict the occurrence of life-threatening hemoptysis. This information helps screen high-risk patients in need of more intensive monitoring for early intervention to improve outcomes. Emergency department CT helps predict life-threatening hemoptysis in patients with lung contusions. Maximal CT ratios ≥ 45.49% (-500 HU to 100 HU, either lung lobe) are associated with life-threatening hemoptysis. High chest abbreviated injury scale scores and hemopneumothorax also predict life-threatening hemoptysis.

Inhalation Exposure to Cross-linked Polyacrylic Acid Induces Pulmonary Disorders.

Organic polymers, widely used in food, daily necessities, and medicines, include cross-linked polyacrylic acid (CL-PAA), which has been reported to induce severe lung disease. While previous studies mainly used intratracheal instillation, our research focused on inhalation exposure to corroborate these findings. We conducted 5-day (short-term) and 13-week (subchronic) inhalation exposure studies with CL-PAA. In the short-term study, male F344 rats inhaled CL-PAA at 0.2, 2.0, or 20mg/m³ for 6hours/day over 5 days. Rats were dissected 3 days and 1 month post-exposure. In the subchronic study, rats inhaled CL-PAA at 0.2 or 2.0mg/m³ for 6hours/day, 5 days/week for 13 weeks, with dissections from 3 days to 6 months post-exposure. To investigate the mechanism of pulmonary disorders, an additional short-term study with 20mg/m³ CL-PAA included intraperitoneal injections of the antioxidant N-acetylcysteine (NAC) (200mg/kg) with dissection the day after exposure. Short-term exposure led to concentration-dependent increases in neutrophil influx, cytokine-induced neutrophil chemoattractant (CINC), total protein, lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in lung tissue. Histopathology showed concentration-dependent neutrophil infiltration. Subchronic exposure caused persistent increases in BALF total protein and lung HO-1, with ongoing neutrophil infiltration and fibrosis. NAC administration reduced neutrophils, total protein, LDH, and CINC in BALF, and HO-1 in lung tissue, improving histopathological findings. Inhalation of CL-PAA caused concentration-dependent lung inflammation and persistent fibrosis. The no observed adverse effect level (NOAEL) for chronic pulmonary disorders was 0.2mg/m³. Oxidative stress linked to CL-PAA-induced inflammation was mitigated by NAC administration.

Abstract 4135534: Total and Regional Lung Volumes And Pulmonary Blood Flow In Repaired Tetralogy Of Fallot - Smaller Lungs And A Maldistribution of Flow

Introduction: Many pts with repaired tetralogy of Fallot (rTOF) are left with residual pulmonary regurgitation (PR) and poor exercise performance. Small studies in young children suggest that the total lung volume of rTOF pts are smaller than normal and may contribute to these sequelae. As exercise and cardiac performance are intimately related to lung function, it’s surprising that few rTOF studies have investigated cardiopulmonary interactions. Aims: To determine if regional and total lung volumes in rTOF pts are the same size as normals and if the larger amount of forward blood flow courses to the bigger lung. We hypothesized that this may not be the case. Methods: rTOF patients undergoing clinically indicated cardiac magnetic resonance (CMR) were evaluated for lung volumes using dark blood imaging (figure) and blood flow to the branch pulmonary arteries (bPA) using velocity mapping. Significance &lt; P=0.05. Results: Eleven rTOF patients and 25 normal controls were studied. Total control lung volume was significantly larger than those of rTOF. Regional rTOF right and left lung volumes were smaller than their respective control lung volumes, barely missed statistical significance (table). In 6 rTOF pts with CMR prior to and after pulmonary valve replacement (PVR), lung volumes did not differ between the 2 timepoints (1034 vs 998 cc/m 2 respectively). Only 3/11 (27%) rTOF pts had the higher bPA flow coursing to the higher regional lung. The ratio of right bPA forward flow/right lung volume to left bPA forward flow/left lung volume ranged from 0.72-1.51 (ideal balanced flow to each lung would be 1), implying a maldistribution of flow. Conclusion: rTOF patients have smaller total lung volumes than controls with no change after PVR in our study. In addition, only a small proportion of rTOF patients have the larger amount of flow coursing to the larger lung. The ratio of individual bPA flow to individual lung volume implies a maldistribution of pulmonary flow relative to the respective lung volume. Our findings may have implications for timing of PVR, partially explaining PR and poor exercise performance. Flow limiters placed by cath or surgery may be able to redistribute the appropriate flow to regional lung fields.

Decreases in lung volume and lung height among ankylosing spondylitis patients with pulmonary function impairment: a 3D CT investigation

BackgroundRespiratory 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.MethodsA 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.ResultsAmong 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.ConclusionsIn 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.

Update of prognosis and characteristics of chronic obstructive pulmonary disease in a real-world setting: a 5-year follow-up analysis of a multi-institutional registry

BackgroundWe conducted a prospective observational study to elucidate the long-term prognosis and management of chronic obstructive pulmonary disease (COPD) in clinical practice in Japan in the mid-2010s.MethodsThis prospective cohort study included 29 facilities. Data from 427 patients clinically diagnosed with COPD, enrolled between September 2013 and April 2016, were analyzed. Interstitial pneumonia was excluded through a central multidisciplinary discussion. Follow-up data were collected for up to 5 years after patient registration.ResultsAt the time of registration, 53 patients clinically diagnosed with COPD did not have airflow limitation (AFL). In the cohort with AFL (n = 374), 232 patients completed a 5-year follow-up, while 49 patients died during the 1576.6 person-years of observation. The mean age was 71.7 years with an overall 5-year survival rate of 85.4%. Stratified by % forced expiratory volume in one second (FEV1), survival rates were 93.6% in the mild and moderate AFL group, 82.5% in the severe AFL group, and 66.1% in the very severe AFL group. The prognosis of the subpopulation without AFL was poor with a 5-year survival of 81.6%. This subpopulation exhibited respiratory symptoms, low vital capacity and total lung capacity, and emphysematous changes.ConclusionsOur study presents the 5-year survival and real-world clinical practice scenario of a prospective cohort of patients clinically diagnosed with COPD in Japan in the mid-2010s. The survival rates of our cohort were numerically better than the Japanese cohort in the 1990s, regardless of the high median age of this cohort. Overall, 12.4% of the patients in this cohort with no AFL at registration exhibited respiratory symptoms and distinct spirometric patterns, and had a poor prognosis.

Associations of pulmonary microvascular blood volume with per cent emphysema and CT emphysema subtypes in the community: the MESA Lung study

BackgroundPulmonary microvasculature alterations are implicated in emphysema pathogenesis, but the association between pulmonary microvascular blood volume (PMBV) and emphysema has not been directly assessed at scale, and prior studies have...

Pulmonary hypertension associated with COPD: a phenotype analysis

BackgroundPulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD; PH-COPD) exhibits diverse phenotypes, challenging therapeutic management. This study aimed to describe the characteristics of COPD patients with distinct phenotypes: end-stage COPD with or without PH; group 1; other COPD patients with mild-to-moderate precapillary PH-COPD; group 2; and COPD patients with a pulmonary vascular phenotype (PVP); group 3.MethodsWe performed a retrospective analysis of COPD patients who underwent right heart catheterization (RHC) from 2015 to 2022.ResultsEighty-one patients were included in group 1, 37 in group 2, and 35 in group 3. The groups differed in clinical, functional, hemodynamic, and imaging characteristics. Group 1 had significantly marked lung hyperinflation with increased total lung capacity and residual volume, a feature not observed in group 3. These results were confirmed by analysis of chest CT scans, which confirmed varying degrees of emphysema: severe in group 1, moderate in group 2, and mild in group 3, with median total emphysema index of 55% (48–62), 32% (16–49), and 16% (3.4–31), respectively, p&lt;0.0001.ConclusionsOur results highlight the broad spectrum of precapillary PH in COPD, from PH associated with end-stage COPD (phenotype/group 1), characterized by predominant alveolar wall damage with severe emphysema, to PVP (phenotype/group 3), mainly due to pulmonary vascular changes. Phenotype/group 2 represents an intermediate state combining features of both. In the current debate on how to distinguish PH-COPD phenotypes, it might be of interest to include quantitative thresholds for emphysema in future diagnostic and management algorithms.

Flecainide acetate inhalation solution for cardioversion of recent-onset, symptomatic atrial fibrillation: results of the phase 3 RESTORE-1 trial

Abstract Introduction Safe, rapid, and efficacious drugs for acute cardioversion of paroxysmal AF (PAF) are needed. In an open-label, Phase 2 study (INSTANT), orally inhaled flecainide was safe and efficacious for acute conversion of PAF to sinus rhythm (SR).[1, 2] Purpose Evaluate the efficacy and safety of flecainide acetate inhalation solution (FlecIH-103) compared to placebo in patients with short-duration, symptomatic, newly diagnosed, or recurrent PAF. Methods RESTORE-1 was a multicentre, randomized, double-blind, placebo-controlled trial in patients with symptomatic PAF (≤48 hours). Patients received FlecIH-103 at an estimated total lung dose of 120 mg or placebo (3:1) over 8 minutes using a breath-actuated nebulizer and were continuously monitored for 90 minutes (observation period), using a single-lead patch ECG electrode. Results The study was stopped prematurely after 55 of the expected 400 patients had been enrolled due to lower-than-expected flecainide peak plasma levels (197.8 ng/mL; 1.85-fold lower than those observed with the same target dose in INSTANT) and modest efficacy. The Data Monitoring Committee confirmed that there were no safety risks. Fifty-four of the enrolled patients (42 active; 12 placebo) were in AF at the start of inhalation. Baseline characteristics were well-balanced between treatment groups; overall mean age was 59.6 years (SD: 13.5) and 31.5% of patients were female. Cardioversion rates during the observation period in the efficacy population (n=51; 39 active, 12 placebo) were 30.8% (95% CI: 18.5-46.5%) in the active group and 0% (95% CI: 0.0-28.2%) in the placebo group (p=0.04; figure 1). In the active group, the median time to conversion from start of inhalation was 12.8 minutes (IQR: 7.8-25.0 minutes), which includes an 8-minute inhalation period. Among the 12 patients whose AF converted to SR, only 1 (8.3%) still had AF-related symptoms compared to 71.8% of patients whose AF did not convert to SR (p&amp;lt;0.001). Time to discharge-eligible status was 1.6h for patients whose AF cardioverted and 3.3h for those whose AF did not (p=0.002; figure 2). The most common adverse events (AEs; ≥8%) occurring more frequently in the active than the placebo group were the following: dyspnoea (14.3%), dysgeusia (14.3%) and cough (11.9%). No serious AEs or cardiovascular events of special interest (hypotension, ventricular tachycardia, bradycardia, sinus pause, atrial flutter 1:1, other arrhythmias) were reported. Conclusions Orally inhaled flecainide, at approximately half of the targeted dose, was modestly effective and safe. The 1.5-fold lower conversion rate observed in this study, compared to the same dose in the INSTANT trial, is consistent with the lower plasma levels of flecainide achieved. Future studies will be designed to improve drug delivery to yield peak plasma levels of flecainide associated with higher conversion rates.

Feasibility of quantitative evaluation of hemodynamics using SPECT/CT in patients with chronic thromboembolic pulmonary hypertension

Abstract Background A ventilation/perfusion (V/Q) lung scan is recommended in the diagnostic work-up of patients with newly diagnosed pulmonary hypertension to rule out chronic thromboembolic pulmonary hypertension (CTEPH). V/Q single-photon emission computed tomography (SPECT) is considered the method of choice for diagnosis in CTEPH because it allows more precise evaluation than planar imaging. However, the evaluation of lung perfusion using V/Q SPECT imaging remains mainly a qualitative evaluation, and no quantitative method has been established. We hypothesized that the standardized uptake value (SUV) technique in Positron Emission Tomography (PET)-CT, a nuclear imaging technique well suited for quantitative of tumor biology, could be applied to quantitative assessment of lung perfusion. Purpose The purpose of this study was to evaluate the correlation between pulmonary perfusion distribution and hemodynamic data in Tc-labeled large-assembly albumin (99mTc-MAA) SPECT images in order to determine the feasibility of SPECT/CT for quantitative assessment of lung perfusion. Methods Twenty-five patients with CTEPH who underwent BPA and received SPECT-CT were included. Since the injected 99mTc-MAA selectively accumulates only in the lungs, SUV normalization was conducted using each patient’s lung volume, calculated by SPECT/CT and defined as SUV lung volume (LV) . The percentage of lung volume below each SUVLV value in total lung volume on SPECT/CT was examined before BPA, after two procedures of BPA, and six months after a series of BPA, and the correlations with hemodynamic parameters on right heart catheterization at each time point were evaluated. Results The Percent lung volume below SUVLV of 0.7 in total lung volume before BPA, after two procedures of BPA, and six months after a series of BPA had the strongest correlation with mean pulmonary artery pressure (mPAP) (rs; 0.727, p&amp;lt;0.001, Figure 1). The percent lung volume below SUVLV of 0.7 decreased with the BPA procedure in each patient with CTEPH (Figure 2). Furthermore, receiver operating characteristic analysis revealed that a threshold for the percent lung volume below SUVLV of 0.7 of 50.3% or greater could identify mPAP greater than 21 mmHg for right heart catheterization (area under the curve = 0.86, 95% CI 0.78-0.94, p&amp;lt;0.001). Conclusion Percent lung volume below SUVLV of 0.7 in total lung volume using SPECT/CT might reflect the severity of hemodynamics in patients with CTEPH. This method would be feasible for quantitative assessment of lung perfusion, even inter-patient and intra-patient.Figure 1Figure 2

Association of High-Risk Obstructive Sleep Apnea with Artificial Intelligence-Guided, CT-Based Severity Scores in Patients with COVID-19 Pneumonia.

Background: We have previously demonstrated that high-risk obstructive sleep apnea (HR-OSA), based on a modified Berlin Questionnaire (mBQ), is linked to worse clinical outcomes. Chest computed tomography (CT) imaging with the implementation of an artificial intelligence (AI) analysis program has been a valuable tool for the speedy assessment of huge numbers of patients during the COVID-19 epidemic. In the current study, we addressed how the severity of AI-guided, CT-based total opacity ratio (TOR) scores are associated with high-risk OSA and short-term outcomes in the same cohort. Methods: The ratio of the volume of high opacity areas to that of the total lung volume constituted the TOR. We arbitrarily applied thresholds of <5 (no or mild TOR), ≥5 and <15 (moderate TOR), and ≥15 (severe TOR). Results: In total, 221 patients were included. HR-OSA was observed among 11.0% of the no or mild TOR group, 22.2% of the moderate TOR group, and 38.7% of the severe TOR group (p < 0.001). In a logistic regression analysis, HR-OSA was associated with a severe TOR with an adjusted odds ratio of 3.06 (95% confidence interval [CI] 1.27-7.44; p = 0.01). A moderate TOR predicted clinical worsening with an adjusted hazard ratio (HR) of 1.93 (95% CI 1.00-3.72; p = 0.05) and a severe TOR predicted worsening with an HR of 3.06 (95% CI 1.56-5.99; p = 0.001). Conclusions: Our results offer additional radiological proof of the relationship between HR-OSA and worse outcomes in patients with COVID-19 pneumonia. A TOR may also potentially indicate the individuals that are at higher risk of HR-OSA, enabling early intervention and management strategies. The clinical significance of TOR thresholds needs further evaluation in larger samples.

Predicting neonatal mortality prior to discharge from hospital in prenatally diagnosed left congenital diaphragmatic hernia.

To evaluate the association of standardized prenatal imaging parameters and immediate neonatal variables with mortality prior to discharge in infants with isolated left congenital diaphragmatic hernia (LCDH), and to compare the performance of ultrasound- and magnetic resonance imaging (MRI)-based severity grading for the prediction of neonatal mortality. This was a retrospective study of infants with prenatally diagnosed isolated LCDH referred to a single tertiary center between 2008 and 2020. Fetuses with right or bilateral congenital diaphragmatic hernia, additional major structural anomaly or known genetic condition, as well as cases that underwent fetal intervention or declined postnatal intervention, were excluded. Ultrasound and MRI images were reviewed retrospectively. Univariable and multivariable analyses were performed, incorporating prenatal and immediate neonatal factors to analyze the association with neonatal mortality prior to discharge, and a prediction calculator was generated. The performance of ultrasound and that of MRI for the prediction of neonatal mortality were compared. Of 253 pregnancies with fetal CDH, 104 met the inclusion criteria, of whom 77 (74%) neonates survived to discharge. Seventy-five fetuses underwent both prenatal ultrasound and MRI. On multivariable analysis, observed/expected (o/e) lung-to-head ratio and o/e total fetal lung volume were associated independently with neonatal death (adjusted odds ratio, 0.89 (95% CI, 0.83-0.95) and 0.90 (95% CI, 0.84-0.97), respectively), whereas liver position was not. There was no significant difference in predictive performance between using ultrasound and MRI together (area under the receiver-operating-characteristics curve (AUC), 0.85 (95% CI, 0.76-0.93)) compared with using ultrasound alone (AUC, 0.81 (95% CI, 0.72-0.90); P = 0.19). The addition of neonatal parameters (gestational age at birth and small-for-gestational age) did not improve model performance (AUC, 0.87 (95% CI, 0.80-0.95)) compared with the combined ultrasound and MRI model (P = 0.22). There was poor agreement between severity assessment on ultrasound and MRI (Cohen's κ, 0.19). Most discrepancies were seen among cases deemed to be non-severe on ultrasound and severe on MRI, and outcomes were more consistent with MRI-based prognostication. In fetuses with prenatally diagnosed isolated LCDH, mortality prediction using standardized ultrasound and MRI measurements performed reasonably well. In cases classified as non-severe on ultrasound, MRI is recommended, as it may provide more accurate prognostication and assist in the determination of candidacy for fetal intervention. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ultrastructural analysis of lamellar bodies in type II alveolar epithelial cells in the human lung.

Pulmonary surfactant is produced by type II alveolar epithelial cells (AEC2) and stored in lamellar bodies (LBs) prior to secretion. Here, we characterize AEC2 and their LBs in the human lung ultrastructurally and quantitatively. Five human lungs were analyzed by transmission electron microscopy, serial section electron tomography and stereology. A human lung contained about 24 billion AEC2 with a mean size of about 650 µm³. The number of AEC2 as well as the total volume of LBs per lung, about 1.9 mL, strongly correlated with total lung volume. A single AEC2 contained an LB volume of about 74 µm³. This amount was packed in about 324 LBs with a mean size of 0.24 µm³. Three morphologically distinct subpopulations of LBs were identified: 1.) isolated LBs which make up the majority (average 300 per AEC2), 2.) LBs connected to each other via pores (average 23 per AEC2), and 3.) LBs connected to the plasma membrane via a fusion pore (average 1 per AEC2). Along this sequence of subpopulations, the mean size of LBs increased. LBs that are connected either with each other or to the plasma membrane contained about 14% of an AEC2´s LB volume. This is in line with the concept of an intermediate surfactant pool, stored in LBs either directly or indirectly connected to the plasma membrane. In summary, this study provides quantitative reference data on surfactant-storing LBs in AEC2 as well as morphological evidence for an intermediate surfactant pool in the human lung.

Physiological Challenges and Adaptations in Competitive Freediving

Competitive freediving is associated with extreme physiologic challenges due to the effects of apnea, submersion in water, and increased ambient pressure. There has nevertheless been a continued progression of world records across freediving disciplines in recent years, with breath-hold times exceeding 10 minutes, and reaching diving depths beyond 200 meters of seawater. The main physiological determinants of breath-hold endurance are the available oxygen stores, i.e., intrapulmonary gas volume, inspired gas concentration, and rate of oxygen consumption. Other factors such as psychological and inherent factors contribute to the individual tolerance to an increasing respiratory stimulus with prolonged breath-hold duration. A freediving athlete must be able to tolerate apnea to stay underwater long enough to reach great distance or depth and resurface safely. Elite freedivers exhibit somewhat remarkable physiological adaptations such as a more pronounced diving-response and hypercapnia tolerance compared to non-divers, as well as metabolic and cerebrovascular adaptations. To reach great depths, elite freedivers employ a breathing technique called glossophyryngeal insufflation (GI) that is enlarging the ratio of total lung capacity to residual volume, thus, mitigating risk of lung squeeze and increasing intrapulmonary gas volume, and thereby enhancing available oxygen stores. Pulmonary anatomy and physiology could not be accounted to restrict the breath-hold diving depths achieved by competitive athletes. However, the acutely increased intrapulmonary pressure during GI is transmitted to the pulmonary vasculature, thereby eliciting a right ventricular pressure overload, and left ventricular dysfunction that may augment hypotension and syncope during glossopharyngeal insufflation. Due to extreme diffusion gradients between alveolar pN2 and N2 pressures in the body tissues at great depth, N2 will be forced into blood and body tissues during descent, elevating risk of N2 narcosis and decompression illness during deep dives. Breath-hold training and preparation have been shown to enhance breath-hold performance. This review highlights recent data on the profound cardiovascular, respiratory, and gas exchange effects that are observed in competitive freedivers, and discusses possible adaptations and risks for humans.

Can switching from cigarettes to heated tobacco products reduce consequences of pulmonary infection?

While tobacco industry data suggests that switching from combustible cigarettes to heated tobacco products (HTPs), like IQOS, may reduce the users' exposure to respiratory toxicants, it is not known if using HTPs impacts the outcomes of acute respiratory infections. Does switching from cigarettes to HTPs improve responses to pulmonary infection. We conducted experiments in which 3 groups of mice were pre-exposed to cigarette smoke for 8 weeks, followed by 8-week exposure to (1) HTPs (tobacco product switching), (2) air (smoking cessation), or (3) continued exposure to cigarette smoke. Pulmonary bacterial clearance and surrogate markers of lung damage were assessed as study outcomes. Significantly compromised clearance of bacteria from the lungs post-acute challenge occurred in both the switching group and in mice continuously exposed to cigarette smoke. Bacterial clearance, inflammatory T-cell infiltration into the lungs, and albumin leak improved at 12h post-acute challenge in the switching group compared to mice continuously exposed to cigarette smoke. Bacterial clearance, total lung immune-cell infiltration, inflammatory T-cell infiltration into the lungs, the content of total proteins in the BAL, and albumin leak measured post-acute challenge were compromised in the switching group compared to mice in the cessation group. Switching from cigarettes to HTPs did not improve lung myeloperoxidase and neutrophil elastase levels (markers for lung inflammation and damage), which, however, were significantly reduced in the cessation group. This study reveals only a modest improvement in respiratory infection outcomes after switching exposure from cigarettes to HTPs and significantly compromised outcomes compared to a complete cessation of exposure to all tobacco products.

Reference formulas for chest CT-derived lobar volumes in the lung-healthy general population.

Lung hyperinflation, a key contributor to dyspnea in chronic obstructive pulmonary disease (COPD), can be quantified via chest computed tomography (CT). Establishing reference equations for lobar volumes and total lung volume (TLV) can aid in evaluating lobar hyperinflation, especially for targeted lung volume reduction therapies. The Imaging in Lifelines study (ImaLife) comprises 11,729 participants aged 45 and above with analyzed inspiratory low-dose thoracic CT scans. Lung and lobar volumes were measured using an automatic AI-based segmentation algorithm (LungSeg). For the main analysis, participants were excluded if they had self-reported COPD/asthma, lung disease on CT, airflow obstruction on lung function testing, were currently smoking, aged over 80 years, or had height outside the 99% confidence interval. Reference equations for TLV and lobar volumes were determined using linear regression considering age and height, stratified by sex. For the subanalysis, participants who were currently smoking or experiencing airflow obstruction were compared to the group of the main analysis. The study included 7306 lung-healthy participants, 97.5% Caucasian, 43.6% men, with mean age of 60.3 ± 9.5 years. Lung and lobar volumes generally increased with age and height. Men consistently had higher volumes than women when adjusted for height. R2 values ranged from 7.8 to 19.9%. In smokers and those with airway obstruction, volumes were larger than in lung-healthy groups, with the largest increases measured in the upper lobes. The established reference equations for CT-derived TLV and lobar volumes provide a standardized interpretation for individuals aged 45 to 80 of Northern European descent. Question Lobar lung volumes can be derived from inspiratory CT scans, but healthy-lung reference values are lacking. Findings Lung and lobar volumes generally increased with age and height. Reference equations for lung/lobar volumes were derived from a sizeable lung-healthy population. Clinical relevance This study provides reference equations for inspiratory CT-derived lung and lobar volumes in a lung-healthy population, potentially useful for assessing candidates for lung volume reduction therapies, for lobe removal in lung cancer patients, and in case of restrictive pulmonary diseases.

Nintedanib preserves lung growth and prevents pulmonary hypertension in a hyperoxia-induced lung injury model.

Bronchopulmonary dysplasia (BPD), the chronic lung disease associated with prematurity, is characterized by poor alveolar and vascular growth, interstitial fibrosis, and pulmonary hypertension (PH). Although multifactorial in origin, the pathophysiology of BPD is partly attributed to hyperoxia-induced postnatal injury, resulting in lung fibrosis. Recent work has shown that anti-fibrotic agents, including Nintedanib (NTD), can preserve lung function in adults with idiopathic pulmonary fibrosis. However, NTD is a non-specific tyrosine kinase receptor inhibitor that can potentially have adverse effects on the developing lung, and whether NTD treatment can prevent or worsen risk for BPD and PH is unknown. We hypothesize that NTD treatment will preserve lung growth and function and prevent PH in an experimental model of hyperoxia-induced BPD in rats. Newborn rats were exposed to either hyperoxia (90%) or room air (RA) conditions and received daily treatment of NTD or saline (control) by intraperitoneal (IP) injections (1 mg/kg) for 14 days, beginning on postnatal day 1. At day 14, lung mechanics were measured prior to harvesting lung and cardiac tissue. Lung mechanics, including total respiratory resistance and compliance, were measured using a flexiVent system. Lung tissue was evaluated for radial alveolar counts (RAC), mean linear intercept (MLI), pulmonary vessel density (PVD), and pulmonary vessel wall thickness (PVWT). Right ventricular hypertrophy (RVH) was quantified with cardiac weights using Fulton's index (ratio of right ventricle to the left ventricle plus septum). When compared with RA controls, hyperoxia exposure reduced RAC by 64% (p < 0.01) and PVD by 65% (p < 0.01) and increased MLI by 108% (p < 0.01) and RVH by 118% (p < 0.01). Hyperoxia increased total respiratory resistance by 94% and reduced lung compliance by 75% (p < 0.01 for each). NTD administration restored RAC, MLI, RVH, PVWT and total respiratory resistance to control values and improved PVD and total lung compliance in the hyperoxia-exposed rats. NTD treatment of control animals did not have adverse effects on lung structure or function at 1 mg/kg. When administered at higher doses of 50 mg/kg, NTD significantly reduced alveolar growth in RA controls, suggesting dose-related effects on normal lung structure. We found that NTD treatment preserved lung alveolar and vascular growth, improved lung function, and reduced RVH in experimental BPD in infant rats without apparent adverse effects in control animals. We speculate that although potentially harmful at high doses, NTD may provide a novel therapeutic strategy for prevention of BPD and PH. Anti-fibrotic therapies may be a novel therapeutic strategy for the treatment or prevention of BPD. High-dose anti-fibrotics may have adverse effects on developing lungs, while low-dose anti-fibrotics may treat or prevent BPD. There is very little preclinical and clinical data on the use of anti-fibrotics in the developing lung. Dose timing and duration of anti-fibrotic therapies may be critical for the treatment of neonatal lung disease. Currently, strategies for the prevention and treatment of BPD are lacking, especially in the context of lung fibrosis, so this research has major clinical applicability.

Quantitative CT-analysis of over aerated lung tissue and correlation with fibrosis extent in patients with idiopathic pulmonary fibrosis

IntroductionThe usual interstitial pneumonia (UIP) pattern, hallmark of idiopathic pulmonary fibrosis (IPF), may induce harmful local overdistension during mechanical ventilation given the juxtaposition of different tissue elasticities. Mechanotransduction, linking mechanical stress and strain to molecular pro-fibrotic pathways, likely contributes to fibrosis progression. Understanding the mechanical forces and aeration patterns in the lungs of IPF patients is crucial for unraveling potential mechanisms of disease progression. Quantitative lung computed tomography (CT) can accurately assess the air content of lung regions, thus informing on zonal distension. This study aims to investigate radiological evidence of lung over aeration in spontaneously breathing UIP patients compared to healthy controls during maximal inspiration.MethodsPatients with IPF diagnosis referred to the Center for Rare Lung Diseases of the University Hospital of Modena (Italy) in the period 2020–2023 who underwent High Resolution Computed Tomography (HRCT) scans at residual volume (RV) and total lung capacity (TLC) using standardized protocols were retrospectively considered eligible. Patients with no signs of lung disease at HRCT performed with the same image acquisition protocol nor at pulmonary function test (PFTs) served as controls. Lung segmentation and quantitative analysis were performed using 3D Slicer software. Lung volumes were measured, and specific density thresholds defined over aerated and fibrotic regions. Comparison between over aerated lung at RV and TLC in the two groups and according to lung lobes was sought. Further, the correlation between aerated lung and the extent of fibrosis was assessed and compared at RV and TLC.ResultsIPF patients (N = 20) exhibited higher over aerated lung proportions than controls (N = 15) both at RV and TLC (4.5% vs. 0.7%, p < 0.0001 and 13.8% vs. 7%, p < 0.0001 respectively). Over aeration increased significantly from RV to TLC in both groups, with no intergroup difference (p = 0.67). Sensitivity analysis revealed significant variations in over aerated lung areas among lobes when passing from RV to TLC with no difference within lobes (p = 0.28). Correlation between over aeration and fibrosis extent was moderate at RV (r = 0.62, p < 0.0001) and weak at TLC (r = 0.27, p = 0.01), being the two significantly different at interpolation analysis (p < 0.0001).ConclusionsThis study provides the first evidence of radiological signs of lung over aeration in patients with UIP-pattern patients when passing from RV to TLC. These findings offer new insights into the complex interplay between mechanical forces, lung structure, and fibrosis and warrant larger and longitudinal investigations.

The first Japanese case of autosomal dominant cutis laxa with a frameshift mutation in exon 30 of the elastin gene complicated by small airway disease with 8 years of follow-up

BackgroundCutis laxa constitutes a diverse group of connective tissue diseases, both inherited and acquired, characterized by loose skin and varying systemic involvement, including pulmonary lesions. While cutis laxa has been linked to conditions like emphysema, asthma, and bronchiectasis, the specific pathological and radiological characteristics underlying pulmonary complications related to cutis laxa remain unclear.Case presentationA 36-year-old woman, diagnosed with cutis laxa at birth, presented to our outpatient clinic with severe obstructive ventilatory impairment, evident in pulmonary function tests (expiratory volume in one second (FEV1)/forced vital capacity (FVC): 34.85%; %residual volume [RV]: 186.5%; %total lung capacity [TLC]: 129.2%). Pulmonary function tests also indicated small airway disease (%FEF50%, 7.9%; %FEF75%, 5.7%; and %FEF25–75%, 6.8%). Computed tomography (CT) revealed the lack of normal increase in lung attenuation on expiratory CT scan, with no discernible emphysematous changes. Exome sequencing was performed to confirm the association between the pulmonary lesions and cutis laxa, revealing a frameshift variant in exon 30 of the elastin gene (ELN). Further analysis employing a parametric response map revealed a longitudinal increase in the percentage of functional small airway disease (fSAD) from 37.84% to 46.61% over the 8-year follow-up, despite the absence of overt changes in CT findings, specifically the lack of normal increase in lung attenuation on expiratory CT scan. Over the same follow-up interval, there was a modest reduction of 25.6 mL/year in FEV1 coupled with a significant increase in %RV. Pulmonary function test metrics, reflective of small airway disease, exhibited a continual decline; specifically, %FEF50%, %FEF75%, and %FEF25–75% diminished from 7.9% to 7.0%, 5.7% to 4.6%, and 6.8% to 5.4%, respectively.ConclusionsThis case highlighted an instance of autosomal dominant cutis laxa arising from a frameshift variant in exon 30 of ELN, accompanied by small airway disease. Comprehensive investigation, utilizing quantitative CT analysis, revealed a longitudinal increase in fSAD percentage with a mild reduction in FEV1. These findings indicate that elastin deficiency may not only diminish elastic fibers in the skin but also be implicated in small airway disease by impacting components of the extracellular matrix in the lungs.

Analysis of vertebrotomy treatment in children with congenital scoliosis with unsegmented rod and rib synostosis

BACKGROUND: Congenital anomalies of vertebral development account for 2%–11% of cases in the general structure of nosologies that cause spinal deformity. An unsegmented rod (unilateral violation of vertebral segmentation) is attributed to a prognostically unfavorable malformation. Rib synostosis causes the development of thoracic insufficiency syndrome. AIM: To analyze the results of treatment of children with congenital scoliosis caused by an unsegmented rod and rib synostosis by vertebrotomy. MATERIALS AND METHODS: This cohort, retrospective, monocenter study evaluated the treatment results of 55 patients. The patients were divided into two groups: group 1, children aged 2–8 years, the scope of intervention was wedge-shaped osteotomy of a non-segmented rod at the apex of the deformity, and group 2, children aged 8–18 years, the scope of intervention was wedge-shaped osteotomy at the apex of the deformity and two linear osteotomies of a non-segmented rod in the cranial and caudal directions. Clinical, radiological, and statistical research methods were used. RESULTS: Significant correction of scoliosis was achieved in 65.5% of patients aged 2–7 years (group 1) and 56.3% in children aged 8–18 years (group 2). Hypokyphosis of the thoracic spine was observed in the patients. The percentage of correction of kyphosis was 21.1% in group 1 and 19.1% in group 2. Lung volume increased by 27.9% (p = 0.01776) in group 1, and lung volume on the concave side increased by 23.5% (p = 0.04975) and on the convex side by 29.6% (p = 0.01073). Improvement in the overall respiratory impedance reached 47.3% (p 0.05). In group 2, a insignificant increase was found in VVC by 12.6% (p = 0.3509) and FEV1 by 8.7% of the initial (p = 0.1534), as well as an increase in total lung volume of 13.3% (p = 0.1527) and the contribution of the lung along the concave side of 18.8% (p = 0.1535), and the lung along the convex side was 8.4% (p = 0.169), indicating no significant impact on lung development and function. CONCLUSIONS: In children with spinal deformity caused by a non-segmented rod with normal respiratory function, vertebrotomy at the apex of the deformity with subsequent correction and stabilization of the spinal deformity is recommended. Performing simultaneous multilevel osteotomies of a non-segmented rod allows for significant correction of rigid spinal deformity.

Quantitative computed tomography assessment of pulmonary function and compensation after lobectomy and segmentectomy in lung cancer patients.

The effect of different surgical methods on postoperative lung function in patients with lung cancer is still inconclusive. The main objective of this study was to compare the effects of video-assisted thoracic surgery (VATS) lobectomy and segmentectomy on postoperative pulmonary function and compensatory changes in patients undergoing lung cancer surgery. A total of 120 patients (82 VATS lobectomy, 38 VATS segmentectomy) were assessed for demographic characteristics, baseline pulmonary function, tumor volume, T stage, and histological grade. Postoperative pulmonary function and compensatory changes [percentage of the well-aerated lung (WAL) total (or unilateral) lung volume (LV) (WAL%) and non-operated lung (NOL)] were measured at multiple time points up to 2 years. Logistic regression analysis identified factors associated with WAL% decline after 1 year. Both VATS lobectomy and segmentectomy led to a decrease in pulmonary function, with no significant difference in the extent of decline between the two groups (all P>0.05). Lobectomy triggered a more pronounced compensatory response, characterized by increased ipsilateral NOL volume over time. Segmentectomy induced minimal compensatory changes and had a minimal impact on pulmonary function. Factors associated with decreased pulmonary ventilation after 1 year differed between the lobectomy and segmentectomy groups. In the lobectomy group, a higher preoperative WAL% of ipsilateral NOL [odds ratio (OR) =1.073; 95% confidence interval (CI): 1.017-1.133; P=0.01] was associated with a higher risk of decline in pulmonary function, whereas in the segmentectomy group, the only influencing factor was the preoperative contralateral mean lung density (MLD) (OR =0.932; 95% CI: 0.884-0.984; P=0.01). Both lobectomy and segmentectomy after lung cancer surgery result in a decrease in WAL%, with lobectomy demonstrating a stronger pulmonary compensatory capacity. The application of quantitative computed tomography (CT) has shown significant value in predicting postoperative pulmonary function preservation and compensatory changes, providing strong support for personalized surgical decision-making.