Extracorporeal photopheresis (ECP) in the treatment of chronic lung allograft dysfunction (CLAD): a prospective, multicentre, open-label, randomised controlled trial studying the addition of ECP to standard care in the treatment of bilateral lung transplant patients with CLAD (E-CLAD UK).

BACKGROUND: Long-term survival after lung transplantation is limited compared with other organ transplants. The main cause is development of progressive immune-mediated damage to the lung allograft. This damage, which can develop via multiple immune pathways, is captured under the umbrella term chronic lung allograft dysfunction (CLAD). Despite the availability of powerful immunosuppressive drugs, there are presently no treatments proven to reverse or reliably halt the loss of lung function caused by CLAD. The aim of the E-CLAD UK trial is to determine whether the addition of immunomodulatory therapy, in the form of extracorporeal photopheresis (ECP), to standard care is more efficacious at stabilising lung function in CLAD compared with standard care alone. METHODS AND ANALYSIS: E-CLAD UK is a Phase II clinical trial of an investigational medicinal product (Methoxsalen) delivered to a buffy coat prepared via an enclosed ECP circuit. Target recruitment is 90 bilateral lung transplant patients identified as having CLAD and being treated at one of the five UK adult lung transplant centres. Participants will be randomised 1:1 to intervention plus standard of care, or standard of care alone. Intervention will comprise nine ECP cycles spread over 20 weeks, each course involving two treatments of ECP on consecutive days. All participants will be followed up for a period of 24 weeks.The primary outcome is lung function stabilisation derived from change in forced expiratory volume in one second and forced vital capacity at 12 and 24 weeks compared with baseline at study entry. Other parameters include change in exercise capacity, health-related quality of life and safety. A mechanistic study will seek to identify molecular or cellular markers linked to treatment response and qualitative interviews will explore patient experiences of CLAD and the ECP treatment.A patient and public advisory group is integral to the trial from design to implementation, developing material to support the consent process and interview materials. ETHICS AND DISSEMINATION: The East Midlands-Derby Research Ethics Committee has provided ethical approval (REC 22/EM/0218). Dissemination will be via publications, patient-friendly summaries and presentation at scientific meetings. TRIAL REGISTRATION NUMBER: EudraCT number 2022-002659-20; ISRCTN 10615985.

Twenty four-month follow-up after bullectomy, unilateral and bilateral lung volume reduction surgery: a single-center retrospective analysis of consecutive cases.

PURPOSE: While pharmacologic therapy remains the cornerstone of lung emphysema treatment, surgery is an additional therapeutic option in selected patient groups with advanced emphysema. The aim of lung volume reduction surgery (LVRS) is to improve lung function, exercise capacity, quality of life and survival. We sought to determine the therapeutic value of surgical resection in specific patients with lung emphysema. PATIENTS AND METHODS: A retrospective study was performed consisting of 58 patients with lung emphysema who underwent surgical intervention over a 10-year period and were followed for 2 years postoperatively. The clinical characteristics recorded were FEV1 (forced expiratory volume in 1 s), the 6-min walk test (6-MWT), the Modified Medical Research Council (mMRC), body mass index (BMI) and quality of life prior to and 6, 12 and 24 months after surgical intervention. Moreover, all peri- and post-operative complications were noted. RESULTS: Out of 58 emphysema patients (72% male, FEV1 (L) 2.21 ± 0.17, RV (L) 3.39 ± 0.55), 19 underwent surgical bullectomy, 31 unilateral LVRS and 8 sequential bilateral LVRS. Six months after surgery, there was a statistically significant improvement in FEV1, RV, TLC, 6-MWT and mMRC. Over a period of 12 to 24 months postoperatively, clinical benefit gradually declines most likely due to COPD progression but patients still experienced a significant improvement in FEV1. The most common postoperative complications were persistent air leakage (> 7 days), arrhythmia and subcutaneous emphysema in 60%, 51.6% and 22.4%, respectively. No deaths were observed after surgical intervention. CONCLUSION: In a selected patient population, surgery led to significant improvement of lung function parameters, exercise capacity and quality of life. Over a period of 12 to 24 months postoperatively, clinical benefit gradually decreased most likely due to COPD progression.

Comparison of limited driving pressure ventilation and low tidal volume strategies in adults with acute respiratory failure on mechanical ventilation: a randomized controlled trial.

BACKGROUND: Ventilator-induced lung injury (VILI) presents a grave risk to acute respiratory failure patients undergoing mechanical ventilation. Low tidal volume (LTV) ventilation has been advocated as a protective strategy against VILI. However, the effectiveness of limited driving pressure (plateau pressure minus positive end-expiratory pressure) remains unclear. OBJECTIVES: This study evaluated the efficacy of LTV against limited driving pressure in preventing VILI in adults with respiratory failure. DESIGN: A single-centre, prospective, open-labelled, randomized controlled trial. METHODS: This study was executed in medical intensive care units at Siriraj Hospital, Mahidol University, Bangkok, Thailand. We enrolled acute respiratory failure patients undergoing intubation and mechanical ventilation. They were randomized in a 1:1 allocation to limited driving pressure (LDP; ⩽15 cmH2O) or LTV (⩽8 mL/kg of predicted body weight). The primary outcome was the acute lung injury (ALI) score 7 days post-enrolment. RESULTS: From July 2019 to December 2020, 126 patients participated, with 63 each in the LDP and LTV groups. The cohorts had the mean (standard deviation) ages of 60.5 (17.6) and 60.9 (17.9) years, respectively, and they exhibited comparable baseline characteristics. The primary reasons for intubation were acute hypoxic respiratory failure (LDP 49.2%, LTV 63.5%) and shock-related respiratory failure (LDP 39.7%, LTV 30.2%). No significant difference emerged in the primary outcome: the median (interquartile range) ALI scores for LDP and LTV were 1.75 (1.00-2.67) and 1.75 (1.25-2.25), respectively (p = 0.713). Twenty-eight-day mortality rates were comparable: LDP 34.9% (22/63), LTV 31.7% (20/63), relative risk (RR) 1.08, 95% confidence interval (CI) 0.74-1.57, p = 0.705. Incidences of newly developed acute respiratory distress syndrome also aligned: LDP 14.3% (9/63), LTV 20.6% (13/63), RR 0.81, 95% CI 0.55-1.22, p = 0.348. CONCLUSIONS: In adults with acute respiratory failure, the efficacy of LDP and LTV in averting lung injury 7 days post-mechanical ventilation was indistinguishable. CLINICAL TRIAL REGISTRATION: The study was registered with the ClinicalTrials.gov database (identification number NCT04035915).

Limited breathing pressure or low amount of air given to the lung; which one is better for adults who need breathing help by ventilator machineWe conducted this research at Siriraj Hospital in Bangkok, Thailand, aiming to compare two ways of helping patients with breathing problems. We studied 126 patients who were randomly put into two groups. One group received a method where the pressure during breathing was limited (limited driving pressure: LDP), and the other group got a method where the amount of air given to the lungs was kept low (low tidal volume: LTV). We checked how bad the lung injury was at seven days later. The results showed that there was no difference between the two methods. Both ways of helping patients breathe had similar outcomes, and neither was significantly better than the other in preventing lung problems. The study suggests that both approaches work about the same for patients who need help with breathing using a machine.

Single and multiple breath nitrogen washout compared with the methacholine test in patients with suspected asthma and normal spirometry.

BACKGROUND: Methods used to assess ventilation heterogeneity through inert gas washout have been standardised and showed high sensitivity in diagnosing many respiratory diseases. We hypothesised that nitrogen single or multiple breath washout tests, respectively nitrogen single breath washout (N2SBW) and nitrogen multiple breath washout (N2MBW), may be pathological in patients with clinical suspicion of asthma but normal spirometry. Our aim was to assess whether N2SBW and N2MBW are associated with methacholine challenge test (MCT) results in this population. We also postulated that an alteration in SIII at N2SBW could be detected before the 20% fall of forced expiratory volume in the first second (FEV1) in MCT. STUDY DESIGN AND METHODS: This prospective, observational, single-centre study included patients with suspicion of asthma with normal spirometry. Patients completed questionnaires on symptoms and health-related quality-of-life and underwent the following lung function tests: N2SBW (SIII), N2MBW (Lung clearance index (LCI), Scond, Sacin), MCT (FEV1 and sGeff) as well as N2SBW between each methacholine dose. RESULTS: 182 patients were screened and 106 were included in the study, with mean age of 41.8±14 years. The majority were never-smokers (58%) and women (61%). MCT was abnormal in 48% of participants, N2SBW was pathological in 10.6% at baseline and N2MBW abnormality ranged widely (LCI 81%, Scond 18%, Sacin 43%). The dose response rate of the MCT showed weak to moderate correlation with the subsequent N2SBW measurements during the provocation phases (ρ 0.34-0.50) but no correlation with N2MBW. CONCLUSIONS: Both MCT and N2 washout tests are frequently pathological in patients with suspicion of asthma with normal spirometry. The weak association and lack of concordance across the tests highlight that they reflect different but not interchangeable pathological pathways of the disease.

Singing for lung health in COPD: a multicentre randomised controlled trial of online delivery.

BACKGROUND: Singing for lung health (SLH) is an arts-based breathing control and movement intervention for people with long-term respiratory conditions, intended to improve symptoms and quality of life. Online, remotely delivered programmes might improve accessibility; however, no previous studies have assessed the effectiveness of this approach. METHODS: We conducted an assessor-blind randomised controlled trial comparing the impact of 12 weeks of once-weekly online SLH sessions against usual care on health-related quality of life, assessed using the RAND 36-Item Short Form Health Survey (SF-36) Mental Health Composite (MHC) and Physical Health Composite (PHC) scores. RESULTS: We enrolled 115 people with stable chronic obstructive pulmonary disease (COPD), median (IQR) age 69 (62-74), 56.5% females, 80% prior pulmonary rehabilitation, Medical Research Council dyspnoea scale 4 (3-4), forced expiratory volume in 1 s % predicted 49 (35-63). 50 participants in each arm completed the study. The intervention arm experienced improvements in physical but not mental health components of RAND SF-36; PHC (regression coefficient (95% CI): 1.77 (95% CI 0.11 to 3.44); p=0.037), but not MHC (0.86 (95% CI -1.68 to 3.40); p=0.504). A prespecified responder analysis based on achieving a 10% improvement from baseline demonstrated a response rate for PHC of 32% in the SLH arm and 12.7% for usual care (p=0.024). A between-group difference in responder rate was not found in relation to the MHC (19.3% vs 25.9%; p=0.403). DISCUSSION AND CONCLUSION: A 12-week online SLH programme can improve the physical component of quality of life for people with COPD, but the overall effect is relatively modest compared with the impact seen in research using face-to-face group sessions. Further work on the content, duration and dose of online interventions may be useful. TRIAL REGISTRATION NUMBER: NCT04034212.

Bronchoscopic Lung Volume Reduction as the Treatment of Choice versus Robotic-Assisted Lung Volume Reduction Surgery in Similar Patients with Emphysema - An Initial Experience of the Benefits and Complications.

Objective: There is an assumption that because EBLVR requires less use of hospital resources, offsetting the higher cost of endobronchial valves, it should therefore be the treatment of choice wherever possible. We have tested this hypothesis in a retrospective analysis of the two in similar groups of patients. Methods: In a 4-year experience, we performed 177 consecutive LVR procedures: 83 patients underwent Robot Assisted Thoracoscopic (RATS) LVRS and 94 EBLVR. EBLVR was intentionally precluded by evidence of incomplete fissure integrity or intra-operative assessment of collateral ventilation. Unilateral RATS LVRS was performed in these cases together with those with unsuitable targets for EBLVR. Results: EBLVR was uncomplicated in 37 (39%) cases; complicated by post-procedure spontaneous pneumothorax (SP) in 28(30%) and required revision in 29 (31%). In the LVRS group, 7 (8%) patients were readmitted with treatment-related complications, but no revisional procedure was needed. When compared with uncomplicated EBLVR, LVRS had a significantly longer operating time: 85 (14-82) vs 40 (15-151) minutes (p<0.001) and hospital stay: 7.5 (2-80) vs 2 (1-14) days (p<0.01). However, LVRS had a similar total operating time to both EBLVR requiring revision: 78 (38-292) minutes and hospital stay to EBLVR complicated by pneumothorax of 11.5 (6.5-24.25) days. Use of critical care was significantly longer in RATS group, and it was also significantly longer in EBV with SP group than in uncomplicated EBV group. Conclusion: Endobronchial LVR does use less hospital resources than RATS LVRS in comparable groups if the recovery is uncomplicated. However, this advantage is lost if one includes the resources needed for the treatment of complications and revisional procedures. Any decision to favour EBLVR over LVRS should not be based on the assumption of a smoother, faster perioperative course.

Aerobic exercise training engages the canonical wnt pathway to improve pulmonary function and inflammation in COPD.

BACKGROUND: We studied whether the exercise improves cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) in mice through inhibition of inflammation mediated by Wnt/ß-catenin-peroxisome proliferator-activated receptor (PPAR) γ signaling. METHODS: Firstly, we observed the effect of exercise on pulmonary inflammation, lung function, and Wnt/ß-catenin-PPARγ. A total of 30 male C57BL/6J mice were divided into the control group (CG), smoke group (SG), low-intensity exercise group (LEG), moderate-intensity exercise group (MEG), and high-intensity exercise group (HEG). All the groups, except for CG, underwent whole-body progressive exposure to CS for 25 weeks. Then, we assessed the maximal exercise capacity of mice from the LEG, MEG, and HEG, and performed an 8-week treadmill exercise intervention. Then, we used LiCl (Wnt/ß-catenin agonist) and XAV939 (Wnt/ß-catenin antagonist) to investigate whether Wnt/ß-catenin-PPARγ pathway played a role in the improvement of COPD via exercise. Male C57BL/6J mice were randomly divided into six groups (n = 6 per group): CG, SG, LiCl group, LiCl and exercise group, XAV939 group, and XAV939 and exercise group. Mice except those in the CG were exposed to CS, and those in the exercise groups were subjected to moderate-intensity exercise training. All the mice were subjected to lung function test, lung histological assessment, and analysis of inflammatory markers in the bronchoalveolar lavage fluid, as well as detection of Wnt1, ß-catenin and PPARγ proteins in the lung tissue. RESULTS: Exercise of various intensities alleviated lung structural changes, pulmonary function and inflammation in COPD, with moderate-intensity exercise exhibiting significant and comprehensive effects on the alleviation of pulmonary inflammation and improvement of lung function. Low-, moderate-, and high-intensity exercise decreased ß-catenin levels and increased those of PPARγ significantly, and only moderate-intensity exercise reduced the level of Wnt1 protein. Moderate-intensity exercise relieved the inflammation aggravated by Wnt agonist. Wnt antagonist combined with moderate-intensity exercise increased the levels of PPARγ, which may explain the highest improvement of pulmonary function observed in this group. CONCLUSIONS: Exercise effectively decreases COPD pulmonary inflammation and improves pulmonary function. The beneficial role of exercise may be exerted through Wnt/ß-catenin-PPARγ pathway.

Impaired lung function and lung cancer risk in 461 183 healthy individuals: a cohort study.

BACKGROUND: It has been known that smoking and various lung diseases including lung cancer can cause lung function impairment. However, the impact of different types of lung function impairments, such as preserved ratio impaired spirometry (PRISm) and airflow obstruction (AO), on the incidence and mortality of lung cancer in both general and never-smoker populations remains unclear. We wished to examine the effect of lung function impairments on lung cancer risks. METHODS: This was a retrospective cohort study (1 January 1994 to 31 December 2017) of individuals from a health surveillance programme in Taiwan who underwent baseline spirometry tests at the entry point. PRISm was defined as an FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio >0.7 and FEV1 <0.8, while AO was defined as an FEV1/FVC ratio <0.7. Cox proportional hazards models and cubic spline curves were used to examine the associations between lung function impairments and lung cancer risks. RESULTS: The study included 461,183 individuals, of whom 14.3% had PRISm and 7.9% had AO. A total of 4038 cases of lung cancer and 3314 lung cancer-related deaths were identified during the 23 years of follow-up. Individuals with PRISm and AO exhibited a higher risk of lung cancer incidence and mortality compared with those with normal lung function. The adjusted HRs and 95% CIs were 1.14 (1.03 to 1.26) and 1.23 (1.10 to 1.37) in the overall cohort, and 1.08 (0.93 to 1.24), and 1.23 (1.05 to 1.45) in the never-smoker cohort. The risks of both developing and dying of lung cancer increased with the severity levels of lung function impairments and lower FEV1 values. CONCLUSION: Impaired lung function is associated with increased risks of developing lung cancer and subsequent mortality. The study highlights the importance of considering lung function in lung cancer screening for better candidate selection.

Monitoring lung recruitment.

PURPOSE OF REVIEW: This review explores lung recruitment monitoring, covering techniques, challenges, and future perspectives. RECENT FINDINGS: Various methodologies, including respiratory system mechanics evaluation, arterial bold gases (ABGs) analysis, lung imaging, and esophageal pressure (Pes) measurement are employed to assess lung recruitment. In support to ABGs analysis, the assessment of respiratory mechanics with hysteresis and recruitment-to-inflation ratio has the potential to evaluate lung recruitment and enhance mechanical ventilation setting. Lung imaging tools, such as computed tomography scanning, lung ultrasound, and electrical impedance tomography (EIT) confirm their utility in following lung recruitment with the advantage of radiation-free and repeatable application at the bedside for sonography and EIT. Pes enables the assessment of dorsal lung tendency to collapse through end-expiratory transpulmonary pressure. Despite their value, these methodologies may require an elevated expertise in their application and data interpretation. However, the information obtained by these methods may be conveyed to build machine learning and artificial intelligence algorithms aimed at improving the clinical decision-making process. SUMMARY: Monitoring lung recruitment is a crucial component of managing patients with severe lung conditions, within the framework of a personalized ventilatory strategy. Although challenges persist, emerging technologies offer promise for a personalized approach to care in the future.

Blood miRNAs as Potential Diagnostic Biomarkers for Chronic Obstructive Pulmonary Disease: A Meta-Analysis.

Purpose: Investigate the efficacy of blood microRNAs (miRNAs) as diagnostic biomarkers for Chronic Obstructive Pulmonary Disease (COPD). Patients and Methods: We conducted a comprehensive search in English and Chinese databases, selecting studies based on predetermined criteria. Diagnostic parameters like summarized sensitivity (SSEN), summarized specificity (SSPE), summarized positive likelihood ratio (SPLR), summarized negative likelihood ratio (SNLR), and diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curves were analyzed using a bivariate model. Each parameter was accompanied by a 95% confidence interval (CI). Results: Eighteen high-quality studies were included. For diagnosing COPD with blood miRNAs, the SSEN was 0.83 (95% CI 0.76-0.89), SSPE 0.76 (95% CI 0.70-0.82), SPLR 3.50 (95% CI 2.66-4.60), SNLR 0.22 (95% CI 0.15-0.33), DOR 15.72 (95% CI 8.58-28.77), and AUC 0.86 (95% CI 0.82-0.88). In acute exacerbations, SSEN was 0.85 (95% CI 0.76-0.91), SSPE 0.80 (95% CI 0.73-0.86), SPLR 4.26 (95% CI 3.05-5.95), SNLR 0.19 (95% CI 0.12-0.30), DOR 22.29 (95% CI 11.47-43.33), and AUC 0.89 (95% CI 0.86-0.91). Conclusion: Blood miRNAs demonstrate significant accuracy in diagnosing COPD, both in general and during acute exacerbations, suggesting their potential as reliable biomarkers.

Race Adjustment of Pulmonary Function Tests in the Diagnosis and Management of COPD: A Scoping Review.

Aim: Increasing evidence suggests that the inclusion of self-identified race in clinical decision algorithms may perpetuate longstanding inequities. Until recently, most pulmonary function tests utilized separate reference equations that are race/ethnicity based. Purpose: We assess the magnitude and scope of the available literature on the negative impact of race-based pulmonary function prediction equations on relevant outcomes in African Americans with COPD. Methods: We performed a scoping review utilizing an English language search on PubMed/Medline, Embase, Scopus, and Web of Science in September 2022 and updated it in December 2023. We searched for publications regarding the effect of race-specific vs race-neutral, race-free, or race-reversed lung function testing algorithms on the diagnosis of COPD and COPD-related physiologic and functional measures. Joanna Briggs Institute (JBI) guidelines were utilized for this scoping review. Eligibility criteria: The search was restricted to adults with COPD. We excluded publications on other lung disorders, non-English language publications, or studies that did not include African Americans. The search identified publications. Ultimately, six peer-reviewed publications and four conference abstracts were selected for this review. Results: Removal of race from lung function prediction equations often had opposite effects in African Americans and Whites, specifically regarding the severity of lung function impairment. Symptoms and objective findings were better aligned when race-specific reference values were not used. Race-neutral prediction algorithms uniformly resulted in reclassifying severity in the African Americans studied. Conclusion: The limited literature does not support the use of race-based lung function prediction equations. However, this assertion does not provide guidance for every specific clinical situation. For African Americans with COPD, the use of race-based prediction equations appears to fall short in enhancing diagnostic accuracy, classifying severity of impairment, or predicting subsequent clinical events. We do not have information comparing race-neutral vs race-based algorithms on prediction of progression of COPD. We conclude that the elimination of race-based reference values potentially reduces underestimation of disease severity in African Americans with COPD.

[Differences in the elastic work of breathing of the pulmonary parenchyma in patients with bronchial asthma and COPD].

AIM: To determine and compare the work of breathing to overcome elastic resistance (Ael) in patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) with similar changes in the elastic properties of the parenchyma in the same settings of ventilation disorders (grade 1). MATERIALS AND METHODS: Differences in the manifestations of similar changes in the elastic properties of the lungs in patients with BA and COPD were evaluated. To identify differences, a comparative study was conducted on Аel overcome in BA patients with positive bronchodilator (with salbutamol) and bronchoconstrictor (with methacholine) tests, with reduced and preserved bronchial conductance (groups 1 and 2, respectively), and in COPD patients with negative bronchodilator and bronchoconstrictor tests (group 3). All study patients showed a grade 1 lung ventilation disorder (a decrease in the one-second forced expiratory volume by 15-35%). The results were compared with each other and with the control group (group 4, healthy non-smokers). All study patients were comparable by age and sex. The respiration mechanics was studied using simultaneous registration of spirogram and transpulmonary pressure, and the parameters of bronchial conductance and ventilation were determined using body plethysmopressography using the Jager software and hardware system. RESULTS AND CONCLUSION: In COPD patients, Ael was significantly increased (p>0.05), whereas in both BA groups, it was unchanged. Increased elastic work of breathing in patients with COPD may be associated with the involvement of certain types of contractile elements, which are preserved in patients with BA at the initial stages of the disease.

Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish "focal" from "non-focal" lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation. METHODS: The Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as "focal" or "non-focal". Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for "non-focal" ARDS and lower PEEP and prone positioning for "focal" ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated. DISCUSSION: PEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach. TRIAL REGISTRATION: The PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).

The association between alcohol consumption and pulmonary function: a scoping review.

INTRODUCTION: The health effects of alcohol are well established but the influence on pulmonary function remains debated. Studies indicate that small amounts of alcohol are beneficial and heavy consumption is harmful, suggesting a U-shaped association. Our objective is to determine whether there is an association between alcohol intake and changes in pulmonary function parameters, exploring the potential protective effect of moderate alcohol consumption and the harm caused by heavy drinking. METHODS: A comprehensive search from PubMed, Embase, Cochrane and CINAHL was carried out, and studies were evaluated using the JBI methodological framework for scoping reviews. Two independent reviewers conducted parallel screening and data extraction. A data extraction form was utilised to organise key themes, with qualitative analysis and visual representation of the results. RESULTS: Among 4427 screened abstracts, 179 underwent full-text review, resulting in 30 eligible studies. Of these, 10 showed a negative effect, nine reported no impact, nine exhibited a positive effect and two indicated a nonlinear U-shaped association between alcohol consumption and pulmonary function parameters. CONCLUSION: While the U-shaped curve hypothesis remains unconfirmed by the current literature, there are notable associations. Heavy alcohol consumption appears to negatively affect pulmonary function, while low to moderate intake shows a positive influence in included studies. However, the diversity in study quality, the nonstandardised alcohol intake quantification and the confounding role of smoking challenge definitive conclusions. The need for consistent, long-term international studies is evident to further explore this relationship while addressing the complex interplay between alcohol and smoking.

Evaluation of airway responsiveness and pulmonary function test results among obese and non-obese patients with obstructive sleep apnea syndrome.

OBJECTIVE: In this research, we aimed to elucidate the effect of obstructive sleep apnea syndrome (OSAS) and obesity on pulmonary volumes and bronchial hyperreactivity, and particularly the effect of supine position on pulmonary volume and functions. PATIENTS AND METHODS: This was a prospective, cross-sectional study with a total of 96 patients (age range, 20-65 years). Based on the body mass index (BMI) and Apnea-Hypopnea Index (AHI) scores, the patients were divided into four groups: Group 1: AHI≥15/h, BMI≥30 kg/m2 (n=24), Group 2: AHI≥15/h, BMI<30 kg/m2 (n=24), Group 3: AHI<15/h, BMI≥30 kg/m2 (n=24), and Group 4: AHI<15/h, BMI<30 kg/m2 (n=24). All patients first had static and dynamic pulmonary function tests and carbon monoxide diffusion tests (TLco and Kco) in the sitting and supine positions. A bronchial provocation test with methacholine was applied to all patients in the sitting position one day later. Analysis of variance (ANOVA) and multivariate linear regression was used in the statistical analysis. RESULTS: Airway responsiveness was observed in 4 of the patients included in the study, and there was no statistically significant difference between the groups. A statistically significant decrease was observed in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), total lung capacity (TLC) and functional residual capacity (FRC), especially in  Group 1 in sitting position compared to Group 4 (p=0.001, p=0.001, p=0.025, p=0.043, and p=0.001, respectively). Changes in pulmonary functions in the transition from sitting to a supine position did not show any significant difference in the study groups (p<0.05). We observed no difference in the diffusion capacity in the sitting and supine positions among the groups (p<0.05). CONCLUSIONS: The severity of AHI and BMI particularly affect the lower airway, but changes in the position did not show any significant difference in the study groups.

Mechanical Interactions Between the Upper Airway and the Lungs that Affect the Propensity to Obstructive Sleep Apnea in Health and Chronic Lung Disease.

Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive narrowing and collapse of the upper airways during sleep. It is caused by multiple anatomic and nonanatomic factors but end-expiratory lung volume (EELV) is an important factor as increased EELV can stabilize the upper airway via caudal traction forces. EELV is impacted by changes in sleep stages, body position, weight, and chronic lung diseases, and this article reviews the mechanical interactions between the lungs and upper airway that affect the propensity to OSA. In doing so, it highlights the need for additional research in this area.

Effects of Ninjin'yoeito on Patients with Chronic Obstructive Pulmonary Disease and Comorbid Frailty and Sarcopenia: A Preliminary Open-Label Randomized Controlled Trial.

Purpose: To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin'yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: Patients with COPD (GOLD II or higher) and fatigue were randomly assigned to Group A (n = 28; no medication for 12 weeks, followed by 12-week administration) or B (n= 25; 24-week continuous administration). Visual analog scale (VAS) symptoms of fatigue, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) Dyspnea Scale were examined. Physical indices such asknee extension leg strength and walking speed, skeletal muscle mass index (SMI), and respiratory function test were also measured. Results: VAS fatigue scales in Group B significantly improved after 4, 8, and 12 weeks compared to those in Group A (each p<0.001, respectively). Right and left knee extension leg strength in Group B significantly improved after 12 weeks compared to that in Group A (p=0.042 and p=0.037, respectively). The 1-s walking speed for continued to increase significantly over 24 weeks in Group B (p=0.016, p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001 after 4, 8, 12, 16, 20, and 24 weeks, respectively); it also significantly increased after the administration of Ninjin'yoeito in Group A. In Group B, the SMI significantly increased at 12 weeks in patients with sarcopenia (p=0.025). The CAT scores in Group B significantly improved after 12 weeks compared to those in Group A (p=0.006). The mMRC scores in Group B also significantly improved after 8 and 12 weeks compared to those in Group A (p= 0.045 and p <0.001, respectively). The changes in %FEV1.0 in Group B were significantly improved at 12 and 24 weeks (p=0.039 and p=0.036, respectively). Conclusion: Overall, Ninjin'yoeito significantly improved patients' quality of life, physical activity, muscle mass, and possibly lung function, suggesting that Ninjin'yoeito may improve frailty and sarcopenia in patients with COPD.

Underdiagnosis of COPD: The Japan COPD Real-World Data Epidemiological (CORE) Study.

Purpose: The prevalence of airflow obstruction in Japan is 3.8%-16.9%. This epidemiological study based on a large database aimed to reassess the prevalence of airflow obstruction in Japan and the diagnosis rate of chronic obstructive pulmonary disease (COPD). Patients and Methods: We used data regarding claims from the health insurance union and health checkups provided by JMDC. The present study included a subgroup of individuals aged ≥40 years who underwent health checkups involving spirometry between January and December 2019. The study endpoints were the prevalence of airflow obstruction, COPD diagnosis rate, disease stage, and respiratory function test results. Results: Among 102,190 participants, 4113 (4.0%) had airflow obstruction. The prevalence of airflow obstruction was 5.3% in men and 2.1% in women. Among the study population, 6.8% were current smokers, while 3.4% were never or former smokers. Additionally, the prevalence of COPD increased with age. Approximately 8.4% of participants with airflow obstruction were diagnosed with COPD. Regarding the COPD diagnosis status, participants with airflow obstruction who were diagnosed with COPD were at a more advanced stage than those not diagnosed. Finally, patients diagnosed with COPD had significantly lower FEV1/FVC and FEV1 (p < 0.0001; Wilcoxon rank sum test). Conclusion: The epidemiological study based on a large database determined the COPD diagnosis rate related to airflow obstruction. The COPD diagnosis rate was extremely low among individuals who underwent health checkups, indicating the need for increased awareness about this medical condition. Moreover, primary care physicians should identify patients with suspected COPD and collaborate with pulmonologists to facilitate the early detection of COPD and enhance the COPD diagnosis rate.

Physics-based in silico modelling of microvascular pulmonary perfusion in COVID-19.

Due to its ability to induce heterogenous, patient-specific damage in pulmonary alveoli and capillaries, COVID-19 poses challenges in defining a uniform profile to elucidate infection across all patients. Computational models that integrate changes in ventilation and perfusion with heterogeneous damage profiles offer valuable insights into the impact of COVID-19 on pulmonary health. This study aims to develop an in silico hypothesis-testing platform specifically focused on studying microvascular pulmonary perfusion in COVID-19-infected lungs. Through this platform, we explore the effects of various acinar-level pulmonary perfusion abnormalities on global lung function. Our modelling approach simulates changes in pulmonary perfusion and the resulting mismatch of ventilation and perfusion in COVID-19-afflicted lungs. Using this coupled modelling platform, we conducted multiple simulations to assess different scenarios of perfusion abnormalities in COVID-19-infected lungs. The simulation results showed an overall decrease in ventilation-perfusion (V/Q) ratio with inclusion of various types of perfusion abnormalities such as hypoperfusion with and without microangiopathy. This model serves as a foundation for comprehending and comparing the spectrum of findings associated with COVID-19 in the lung, paving the way for patient-specific modelling of microscale lung damage in emerging pulmonary pathologies like COVID-19.

Pulmonary blood volume measured by 82Rb-PET in patients with chronic obstructive pulmonary disease: a retrospective cohort study.

In patients with chronic obstructive pulmonary disease (COPD), pulmonary vascular dysfunction and destruction are observable before the onset of detectable emphysema, but it is unknown whether this is associated with central hypovolemia. We investigated if patients with COPD have reduced pulmonary blood volume (PBV) evaluated by 82Rb-positron emission tomography (PET) at rest and during adenosine-induced hyperemia. This single-center retrospective cohort study assessed 6,301 82Rb-PET myocardial perfusion imaging (MPI) examinations performed over a 6-yr period. We compared 77 patients with COPD with 44 healthy kidney donors (controls). Cardiac output ([Formula: see text]) and mean 82Rb bolus transit time (MBTT) were used to calculate PBV. [Formula: see text] was similar at rest (COPD: 3,649 ± 120 mL vs. control: 3,891 ± 160 mL, P = 0.368) but lower in patients with COPD compared with controls during adenosine infusion (COPD: 5,432 ± 124 mL vs. control: 6,185 ± 161 mL, P < 0.050). MBTT was shorter in patients with COPD compared with controls at rest (COPD: 8.7 ± 0.28 s vs. control: 11.4 ± 0.37 s, P < 0.001) and during adenosine infusion (COPD: 9.2 ± 0.28 s vs. control: 10.2 ± 0.37 s, P < 0.014). PBV was lower in patients with COPD, even after adjustment for body surface area, sex, and age at rest [COPD: 530 (29) mL vs. 708 (38) mL, P < 0.001] and during adenosine infusion [COPD: 826 (29) mL vs. 1,044 (38) mL, P < 0.001]. In conclusion, patients with COPD show evidence of central hypovolemia, but it remains to be determined whether this has any diagnostic or prognostic impact.NEW & NOTEWORTHY The present study demonstrated that patients with chronic obstructive pulmonary disease (COPD) exhibit central hypovolemia compared with healthy controls. Pulmonary blood volume may thus be a relevant physiological and/or clinical outcome measure in future COPD studies.