Relationships between symptoms and lung function in asthma and/or chronic obstructive pulmonary disease in a real-life setting: the NOVEL observational longiTudinal studY.

BACKGROUND: The relationships between spirometric assessment of lung function and symptoms (including exacerbations) in patients with asthma and/or chronic obstructive pulmonary disease (COPD) in a real-life setting are uncertain. OBJECTIVES: To assess the relationships between baseline post-bronchodilator (post-BD) spirometry measures of lung function and symptoms and exacerbations in patients with a physician-assigned diagnosis of asthma and/or COPD. DESIGN: The NOVEL observational longiTudinal studY (NOVELTY) is a global, prospective, 3-year observational study. METHODS: Logistic regression analysis was used to evaluate relationships. Spirometry measures were assessed as percent predicted (%pred). Symptoms were assessed at baseline, and exacerbations were assessed at baseline and Year 1. RESULTS: A total of 11,181 patients in NOVELTY had spirometry data (asthma, n = 5903; COPD, n = 3881; asthma + COPD, n = 1397). A 10% lower post-BD %pred forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) - adjusted for age and sex - were significantly associated with dyspnea (modified Medical Research Council ⩾ grade 2), frequent breathlessness [St George's Respiratory Questionnaire (SGRQ)], frequent wheeze attacks (SGRQ), nocturnal awakening (Respiratory Symptoms Questionnaire; ⩾1 night/week), and frequent productive cough (SGRQ). Lower post-BD %pred FEV1 and, to a lesser extent, lower post-BD %pred FVC were significantly associated with ⩾1 physician-reported exacerbation at baseline or Year 1. This association was stronger in patients with COPD than in those with asthma. CONCLUSION: In a real-life setting, reduced lung function is consistently associated with symptoms in patients with asthma, COPD, or asthma + COPD. The relationship with exacerbations is stronger in COPD only than in asthma. TRAIL REGISTRATION: clinicaltrials.gov identifier: NCT02760329 (www.clinicaltrials.gov).

Relationships between symptoms and lung function in asthma and/or chronic obstructive pulmonary disease in a study performed in a real-life setting: the NOVELTY studyBackground: Asthma and chronic obstructive pulmonary disease (COPD) have many symptoms in common. To confirm diagnosis, doctors use spirometry, a test to measure the amount of air that can be breathed out from the lungs and how fast it can be blown out. The relationship between these measurements and symptoms in asthma and COPD is not well understood.Objectives: The aim of this research is to describe the characteristics, treatment, and impact of asthma and/or COPD in patients who are receiving their usual medical care.Methods: NOVELTY is a large study of around 12,000 patients across 19 countries. This analysis of NOVELTY looked at the relationships between two spirometry measurements and the symptoms of asthma and/or COPD experienced by patients. The spirometry measurements were: - forced expiratory volume in 1 second (FEV₁) ­ the amount of air that can be blown out of the lungs in 1 second- forced vital capacity (FVC) ­ the amount of air that can be forcibly breathed out from the lungs after taking the deepest breath possibleResults: The lower the FEV₁ and FVC, the more common the symptoms of breathlessness, wheeze attacks, night-time awakening, and coughing up of phlegm or mucus. These relationships were similar for FEV₁ and FVC. Lower FEV₁ was more strongly associated with worse symptoms in COPD than in asthma.Conclusion: These findings help to improve our understanding of the relationships between spirometry measures and symptoms in patients with asthma and/or COPD.

Aerodynamic Simulation of Small Airway Resistance: A New Imaging Biomarker for Chronic Obstructive Pulmonary Disease.

Purpose: To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD. Patients and Methods: 24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (RSA) and RSA as a percentage of total airway resistance (RSA%) were calculated by CFD combined with airway resistance and FEV1 measured by pulmonary function test. A correlation analysis was conducted between RSA and pulmonary function parameters, including FEV1/FVC, FEV1% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted. Results: The RSA and RSA% were significantly different among the three groups (p<0.05) and related to FEV1/FVC (r = -0.70, p < 0.001; r = -0.67, p < 0.001), FEV1% predicted (r = -0.60, p = 0.002; r = -0.57, p = 0.004), MEF50% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001), MEF75% predicted (r = -0.71, p < 0.001; r = -0.60, p = 0.002) and MMEF 75/25% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001). Conclusion: Airway CFD is a valuable method for estimating the small airway resistance, where the derived RSA will aid in the early diagnosis of COPD.

The Effect of Priming new Plastic Spacers with 20 Puffs Salbutamol on Bronchodilator Response in Asthmatic Children.

The static charge on the plastic body of spacers attracts drug aerosols, reducing the drug available for inhalation from plastic spacers. Some instructions exist to decrease the electric charge on plastic spacers, such as priming them with salbutamol (20 puffs) before use. This study investigates whether priming plastic spacer devices with this method can improve the bronchodilator test result. This study included children with stable mild to moderate asthma. All subjects underwent two pulmonary function tests to evaluate their bronchodilator response on separate days at 24-48 hours intervals. On each day, spirometry was performed at the baseline and 15 min after inhalation of four puffs of salbutamol (100 µg/puff) through either a primed or a new spacer. The change in forced expiratory volume in the first second (FEV1) after inhaling salbutamol was the primary outcome measure. When the patients used a new spacer, the mean baseline FEV1 (% predicted) and FEV1/FVC (forced vital capacity) were 89.56±11.95 and 86.17±6.87, respectively. However, the mean increase in FEV1 from the baseline was 10.87±8.99 in this group. On the other hand, with the primed spacer, the respective mean baseline FEV1 and FEV1/FVC values were 89.41±12.14 and 85.49±6.76, while it increased by 12.1±11.01 after salbutamol inhalation. There were no significant differences between the techniques regarding the variation in FEV1 before and after bronchodilator use via a new spacer or primed spacer. Priming new plastic spacers with 20 puffs of salbutamol did not cause additional bronchodilation in asthmatic children, suggesting this practice is inefficient in clinics.

Pulmonary function in Thai patients with systemic sclerosis; a single center 6-year retrospective study.

Background: Pulmonary involvement is a major cause of internal organ complication and the leading cause of death in patients with systemic sclerosis (SSc). This study aimed to demonstrate the characteristics of pulmonary function (PF) in Thai patients with SSc and the association between PF and body mass index (BMI) and anti-topoisomerase (anti-Scl70). Methods: All patients diagnosed with SSc in our tertiary care teaching hospital database between 2016 and 2021 were reviewed and analyzed. Results: Of 211 SSc patients, 128 patients who underwent the PF test were enrolled; 102 (79.7%) were female. The mean age was 54 years. The median BMI for all patients was 21.7 kg/m 2. Regarding anti-Scl70, 10.9% of patients were positive, 7.8% were negative, and the status was unreported for 81.3%. The mean (SD) forced expiratory volume in one second (FEV1) forced vital capacity (FVC) ratio was 0.8 (0.1). The mean (SD) % predicted values of FEV1, FVC, and diffusing capacity of the lungs for carbon monoxide (DLCO) were 76.3 (16.3), 69.1 (15.8), and 75.5 (22.8), respectively. A restrictive spirometry pattern (RSP) was found in 78.8% of the patients. DLCO had a moderate positive linear correlation with FVC (r=0.50, p <0.001) and a moderate negative linear correlation with BMI (r=-0.36, p <0.001). However, there was no correlation between FVC and BMI. There was no statistical difference in demographic data or the presence of anti-Scl70 among patients with or without RSP. Conclusions: RSP is common among Thai patients with SSc. However, the power of using demographic data and the presence of anti-Scl70 to determine the probability of pulmonary involvement remains limited.

Factors affecting prediction accuracy of postoperative FEV1 and DL,CO in patients undergoing lung resection.

INTRODUCTION: Despite significant development in systemic therapy and radiotherapy, surgery is still the cornerstone for curative lung cancer treatment. Although predicted postoperative function (ppo) somewhat exactly correlates with actual postoperative function bigger differences may be a cause of serious clinical outcome.

A randomised trial of oral prednisone for cystic fibrosis pulmonary exacerbation treatment.

BACKGROUND: Elevated markers of systemic and pulmonary inflammation are associated with failure to recover lung function following pulmonary exacerbations in people with cystic fibrosis (pwCF). Our aim was to determine whether adjuvant oral prednisone treatment would improve recovery of forced expiratory volume in 1 s (FEV1) % pred in CF pulmonary exacerbations not responding to antibiotic therapy. METHODS: This was a randomised, double-blind, placebo-controlled trial in pwCF treated with intravenous antibiotics for a pulmonary exacerbation. At day 7, those who had not returned to >90% baseline FEV1 % pred were randomised to adjuvant prednisone 1 mg·kg-1 twice daily (maximum 60 mg·day-1) or placebo for 7 days. The primary outcome was the difference in proportion of subjects who recovered >90% baseline FEV1 % pred at day 14 of i.v. antibiotic therapy. RESULTS: 173 subjects were enrolled, with 76 randomised. 50% of subjects in the prednisone group recovered baseline FEV1 on day 14 compared with 39% of subjects in the placebo group (difference of 11%, 95% CI -11-34%; p=0.34). The mean±sd change in FEV1 % pred from day 7 to day 14 was 6.8±8.8% predicted in the prednisone group and 4.6±6.9% predicted in the placebo group (mean difference 2.2% predicted, 95% CI -1.5-5.9%; p=0.24). Time to subsequent exacerbation was not prolonged in prednisone-treated subjects (hazard ratio 0.83, 95% CI 0.45-1.53; p=0.54). CONCLUSIONS: This study failed to detect a difference in FEV1 % pred recovery between adjuvant oral prednisone and placebo treatment in pwCF not responding at day 7 of i.v. antibiotic therapy for pulmonary exacerbations.

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.

The status and influencing factors of lung ventilation function in employees exposed to dust in enterprises of the XPCC, China.

Background: Occupational health is closely related to harmful factors in the workplace. Dust is the primary contributing factor causing impaired lung ventilation function among employees with dust exposure, and their lung ventilation function may also be influenced by other factors. We aimed at assessing the status and influencing factors of lung ventilation function among employees exposed to dust in the enterprises of the Eighth Division located in the Xinjiang Production and Construction Corps (XPCC), China. Methods: Employees exposed to dust in enterprises of the Eighth Division located in the XPCC in 2023 were selected as the subjects of this cross-sectional study. Their lung ventilation function indicators were extracted from health examination records, and an on-site electronic questionnaire survey was conducted among them. Binary logistic regression analyses were conducted to evaluate the factors influencing lung ventilation function. Results: According to the fixed value criteria, the abnormal rates of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC were 31.6, 1.4, and 0.4%, respectively. The lower limit of normal (LLN) criteria could overestimate the rate of abnormal lung ventilation function. Several factors were related to impaired lung ventilation function, including gender, age, education level, marital status, body mass index (BMI), smoking status, physical activity, the type of dust, industry, enterprise scale, occupation, length of service, working shift, monthly income, and respiratory protection. Conclusions: A relatively low abnormal rate of lung ventilation function was observed among employees exposed to dust in enterprises of the Eighth Division, XPCC, and their lung ventilation function was associated with various factors. Effective measures should be taken urgently to reduce the effects of adverse factors on lung ventilation function, thereby further protecting the health of the occupational population.

Comparison of a portable, pneumotach flow-sensor-based spirometer (Spirofy™) with the vitalograph alpha Touch™ spirometer in evaluating lung function in healthy individuals, asthmatics, and COPD patients-a randomized, crossover study.

BACKGROUND: Spirofy™ is India's first portable, pneumotach flow-sensor-based digital spirometer developed to diagnose asthma and chronic obstructive pulmonary disease (COPD). In this study, we compared the performance of the Spirofy™ device with that of the Vitalograph Alpha Touch™ spirometer in measuring the lung capacities of healthy individuals, asthmatics, and COPD patients. We also assessed the inter-device variability between two Spirofy™ devices. METHODS: In a randomized, three-way crossover, open-label study, we measured the differences in forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) between the Spirofy™ and Vitalograph Alpha Touch™ spirometers. A proportion of the FEV1/FVC ratio distribution of < 0.7 was used to compare the diagnostic accuracies of the Spirofy™ with Vitalograph™ Alpha Touch™ spirometers. RESULTS: Ninety subjects participated in this study. The mean ± SD FVC values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 2.60 ± 1.05 L, 2.64 ± 1.04 L, and 2.67 ± 1.04 L, respectively. The mean ± SD FEV1 values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 1.87 ± 0.92 (L), 1.88 ± 0.92 (L), and 1.93 ± 0.93 (L), respectively. A significant positive correlation was found between the FVC and FEV1 values recorded by Vitalograph Alpha Touch™, Spirofy™ 1, and Spirofy™ 2. As compared to Vitalograph Alpha Touch™, the Spirofy™ device showed good sensitivity (97%), specificity (90%), and overall accuracy (93.3%) at an FEV1/FVC ratio < 0.7. No inter-device variability was observed between the two Spirofy™ devices. CONCLUSION: Spirofy™ is a portable and easy-to-use device and is as accurate as the standard Vitalograph Alpha Touch™ spirometer for the diagnosis of COPD and asthma. TRIAL REGISTRATION: CTRI/2021/09/036492 (Clinical Trials Registry - India).

Association Between FEV1 Decline Rate and Mortality in Long-Term Follow-Up of a 21-Patient Pilot Clinical Trial of Inhaled Liposomal Cyclosporine Plus Standard-of-Care Versus Standard-of-Care Alone for Bronchiolitis Obliterans Syndrome After Lung Transplantation.

BACKGROUND The association between forced expiratory volume in 1 second (FEV1) trajectory and mortality in bronchiolitis obliterans syndrome (BOS) is not well defined. Using long-term data from a prior clinical trial of inhaled liposomal cyclosporine A (L-CsA-I) for lung transplant patients with BOS, this study examined the association between longitudinal FEV1 change and mortality. MATERIAL AND METHODS We analyzed long-term data from a clinical trial which randomized 21 patients with BOS (³20% decrease in FEV1 from personal maximum) to receive L-CsA-I plus standard-of-care (n=11) or standard-of-care (SOC) alone (n=10) for 24 weeks. A joint statistical model, combining a linear mixed model for FEV1 change and Cox regression for mortality, was utilized to examine the overall association between FEV1 trajectory and mortality during follow-up. RESULTS The 21 trial participants (10 single, 11 double lung recipients) had a mean FEV1 of 1.7±0.6 Liters at randomization. Median follow-up post-randomization was 35 months. In joint model analysis, 1 percent FEV1 decline predicted 1.076-fold increased mortality risk (95% confidence interval: -0.998 to 1.160, p=0.058). FEV1 decline was reduced by 2.6% per year in L-CsA-I patients compared to SOC (p=0.210), and overall survival at 1/3/5 years was 91%/64%/27% vs 90%/20%/0% for L-CsA-I versus SOC, respectively (p=0.164). CONCLUSIONS In BOS patients, greater longitudinal FEV1 decline predicts increased mortality. Trends towards prolonged stabilization of FEV1 and improved survival were observed with L-CsA-I receipt. Further analyses will aid in evaluating the utility of FEV1 change as a survival predictor, having implications in BOS management and future trial design.

Internet of Things-Based Home Respiratory Muscle Training for Patients with Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial.

Purpose: Whether Internet of Things (IoT)-based home respiratory muscle training (RMT) benefits patients with comorbid chronic obstructive pulmonary disease (COPD) remains unclear. Therefore, this study aims to evaluate the effectiveness of IoT-based home RMT for patients with COPD. Patients and Methods: Seventy-eight patients with stable COPD were randomly divided into two groups. The control group received routine health education, while the intervention group received IoT-based home RMT (30 inspiratory muscle training [IMT] and 30 expiratory muscle training [EMT] in different respiratory cycles twice daily for 12 consecutive weeks). Assessments took place pre-intervention and 12 weeks post-intervention, including lung function tests, respiratory muscle strength tests, the mMRC dyspnea scale, CAT questionnaires, the HAMA scale, and 6-month COPD-related readmission after intervention. Results: Seventy-four patients with COPD were analyzed (intervention group = 38, control group = 36), and the mean age and FEV1 of the patients were 68.65 ± 7.40 years, 1.21 ± 0.54 L. Compared to those of the control population, the intervention group exhibited higher FEV1/FVC (48.23 ± 10.97 vs 54.32 ± 10.31, p = 0.016), MIP (41.72 ± 7.70 vs 47.82 ± 10.99, p = 0.008), and MEP (42.94 ± 7.85 vs 50.29 ± 15.74, p = 0.013); lower mMRC (2.00 [2.00-3.00] vs 1.50 [1.00-2.00], p < 0.001), CAT (17.00 [12.00-21.75] vs 11.00 [9.00-13.25], p < 0.001), and HAMA (7.00 [5.00-9.00] vs 2.00 [1.00-3.00], p < 0.001) scores; and a lower incidence rate of 6-month readmission (22% vs 5%, p = 0.033). Conclusion: Compared with no intervention, IoT-based home RMT may be a more beneficial intervention for patients with COPD.

Domiciliary monitoring of exhaled nitric oxide in the management of asthma: a pilot study.

BACKGROUND: Whether asthma patients could benefit from home monitoring for fractional exhaled nitric oxide (flow of 50 mL/s, FeNO50) is unknown. We explore the application value of home monitoring FeNO50 in daily asthma management. METHODS: Twenty-two untreated, uncontrolled asthma patients were selected. Medical history, blood and sputum samples, pulmonary function, Asthma Control Test (ACT), and other clinical data of the subjects were collected. All subjects underwent daily monitoring for four weeks using a FeNO50 monitor and mobile spirometry (mSpirometry). The diurnal differences and dynamic changes were described. Compare the effect-acting time and the relative plateau of treatment between FeNO50 and mSpirometry monitoring. RESULTS: In the first two weeks, the morning median (IQR) level of FeNO50 was 44 (35, 56) ppb, which was significantly higher than the evening median level [41 (32, 53) ppb, P = 0.028]. The median (IQR) effect-acting time assessed by FeNO50 was 4 (3, 5) days, which was significantly earlier than each measure of mSpirometry (P < 0.05). FeNO50 reached the relative plateau significantly earlier than FEV1 (15 ± 2 days vs. 21 ± 3 days, P < 0.001). After treatment, the daily and weekly variation rates of FeNO50 showed a gradually decreasing trend (P < 0.05). The ACT score, sputum eosinophils, and blood eosinophils also significantly improved (P ≤ 0.01). CONCLUSIONS: The daily home monitoring of FeNO50 in asthmatic patients showed significant circadian rhythm, and the sensitivity of FeNO50 in evaluating the response to treatment was higher than mSpirometry. The daily and weekly variation rates of FeNO50 change dynamically with time, which may be used to assess the condition of asthma.

Monitoring COPD patients: systemic and bronchial eosinophilic inflammation in a 2-year follow-up.

BACKGROUND: High blood eosinophils seem to predict exacerbations and response to inhaled corticosteroids (ICS) treatment in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate for 2 years, blood and sputum eosinophils in COPD patients treated with bronchodilators only at recruitment. METHODS: COPD patients in stable condition treated with bronchodilators only underwent monitoring of lung function, blood and sputum eosinophils, exacerbations and comorbidities every 6 months for 2 years. ICS was added during follow-up when symptoms worsened. RESULTS: 63 COPD patients were enrolled: 53 were followed for 1 year, 41 for 2 years, 10 dropped-out. After 2 years, ICS was added in 12/41 patients (29%) without any statistically significant difference at time points considered. Blood and sputum eosinophils did not change during follow-up. Only FEV1/FVC at T0 was predictive of ICS addition during the 2 year-follow-up (OR:0.91; 95% CI: 0.83-0.99, p = 0.03). ICS addition did not impact on delta (T24-T0) FEV1, blood and sputum eosinophils and exacerbations. After 2 years, patients who received ICS had higher blood eosinophils than those in bronchodilator therapy (p = 0.042). Patients with history of ischemic heart disease increased blood eosinophils after 2 years [p = 0.03 for both percentage and counts]. CONCLUSIONS: Blood and sputum eosinophils remained stable during the 2 year follow-up and were not associated with worsened symptoms or exacerbations. Almost 30% of mild/moderate COPD patients in bronchodilator therapy at enrollment, received ICS for worsened symptoms in a 2 year-follow-up and only FEV1/FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils.

Clinical features and 1-year outcomes of variable obstruction in participants with preserved spirometry: results from the ECOPD study in China.

BACKGROUND: There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes. METHODS: Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC <0.70) were compared with those without variable obstruction (prebronchodilator FEV1/FVC ≥0.70). We performed subgroup analyses in never smokers, former and current smokers, and different variable obstruction types (postbronchodilator FVC

Phase 1 Study of MK-5475, an Inhaled Soluble Guanylate Cyclase Stimulator, in Participants with Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease.

Purpose: This phase 1 study (NCT04370873) evaluated safety and pharmacokinetics/pharmacodynamics (PK/PD) of MK-5475 in participants with pulmonary hypertension associated with COPD (PH-COPD). Methods: Eligible participants were 40-80 years old with COPD (FEV1/FVC <0.7; FEV1 >30% predicted) and PH (mean pulmonary arterial pressure ≥25 mmHg). Participants were randomized 2:1 to MK-5475 or placebo via dry-powder inhaler once daily for 7 days in Part 1 (360 µg) or 28 days in Part 2 (380 µg). Safety was assessed by adverse events (AEs) and arterial blood oxygenation. Part-2 participants had pulmonary vascular resistance (PVR; primary PD endpoint) and pulmonary blood volume (PBV; secondary PD endpoint) measured at baseline and Day 28. A non-informative prior was used to calculate posterior probability (PP) that the between-group difference (MK-5475 - placebo) in mean percent reduction from baseline in PVR was less than -15%. Results: Nine participants were randomized in Part 1, and 14 participants in Part 2. Median age of participants (86.4% male) was 68.5 years (41-77 years); 95.5% had moderate-to-severe COPD. Incidences of AEs were comparable between MK-5475 and placebo: overall (5/14 [36%] versus 5/8 [63%]), drug-related (1/14 [7%] versus 2/8 [25%]), and serious (1/14 [7%] versus 1/8 [13%]). MK-5475 caused no meaningful changes in arterial blood oxygenation or PBV. MK-5475 versus placebo led to numerical improvements from baseline in PVR (-21.2% [95% CI: -35.4, -7.0] versus -5.4% [95% CI: -83.7, 72.9]), with between-group difference in PVR less than -15% and calculated PP of 51%. Conclusion: The favorable safety profile and numerical reductions in PVR observed support further clinical development of inhaled MK-5475 for PH-COPD treatment.

Management Reality of Female Patients with COPD: A Multicenter Cross-Sectional CAP Study in Japan.

Background: Reports from Europe and North America suggest that female chronic obstructive pulmonary disease (COPD) patients have a higher symptom burden and mortality than male patients. However, little is known about the management reality of female patients with COPD in Japan. Patients and Methods: We compared the clinical characteristics of female COPD patients with those of male using the cohort of the COPD Assessment in Practice study, which is a cross-sectional multicenter observational study. Results: Of the 1168 patients, 133 (11.4%) were female. A history of never smoking was higher in females than males (p<0.01). Although there was no difference in age or forced expiratory volume in one second (FEV1) % predicted between the groups, modified medical research council dyspnea scale (mMRC) and number of frequent exacerbators were higher in females (mMRC≥2: p<0.01; number of exacerbations≥2: p=0.011). The mean forced vital capacity and FEV1 values in females were lower than those in males (p<0.0001 and p<0.0001, respectively). Females were more likely to use long-term oxygen therapy and inhaled corticosteroids than males (p=0.016 and p<0.01, respectively). The prevalence of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups B, C, D (ABCD GOLD 2017 classification), and E (ABE GOLD 2023 classification) was higher in females than in males. Conclusion: The disease burden of female patients with COPD is higher than that of male patients in Japan, suggesting the importance of interventions considering female-dominant features such as lower absolute FVC and FEV1, respiratory failure, and asthma-like conditions.

Cross-shift changes in pulmonary function and occupational exposure to particulate matter among e-waste workers in Ghana.

Introduction: Little is known on the association between cross-shift changes in pulmonary function and personal inhalation exposure to particulate matter (PM) among informal electronic-waste (e-waste) recovery workers who have substantial occupational exposure to airborne pollutants from burning e-waste. Methods: Using a cross-shift design, pre- and post-shift pulmonary function assessments and accompanying personal inhalation exposure to PM (sizes <1, <2.5 µm, and the coarse fraction, 2.5-10 µm in aerodynamic diameter) were measured among e-waste workers (n = 142) at the Agbogbloshie e-waste site and a comparison population (n = 65) in Accra, Ghana during 2017 and 2018. Linear mixed models estimated associations between percent changes in pulmonary function and personal PM. Results: Declines in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) per hour were not significantly associated with increases in PM (all sizes) among either study population, despite breathing zone concentrations of PM (all sizes) that exceeded health-based guidelines in both populations. E-waste workers who worked "yesterday" did, however, have larger cross-shift declines in FVC [-2.4% (95%CI: -4.04%, -0.81%)] in comparison to those who did not work "yesterday," suggesting a possible role of cumulative exposure. Discussion: Overall, short-term respiratory-related health effects related to PM exposure among e-waste workers were not seen in this sample. Selection bias due to the "healthy worker" effect, short shift duration, and inability to capture a true "pre-shift" pulmonary function test among workers who live at the worksite may explain results and suggest the need to adapt cross-shift studies for informal settings.

Prevalence, Medicaid use and mortality risk of low FEV1 in adults aged 20-35 years old in the USA: evidence from a population-based retrospective cohort study.

BACKGROUND: The prevalence, Medicaid use and mortality risk associated with low forced expiratory volume in 1 s (FEV1) among young adults aged 20-35 years are not well understood, despite its potential implications for the development of chronic pulmonary disease and overall prognosis. METHODS: A retrospective cohort study was conducted among young adults aged 20-35 years old, using data from the National Health and Nutrition Examination Survey, National Death Index and Centers for Medicare & Medicaid Services. Participants were categorised into a low FEV1 group (pre-bronchodilator FEV1%pred <80%) and a normal FEV1 group (FEV1%pred ≥80%). Weighted logistic regression analysis was employed to identify the risk factors associated with low FEV1, while Cox proportional hazard models were used to calculate the hazard ratio (HR) for Medicaid use and the all-cause mortality between the two groups. RESULTS: A total of 5346 participants aged 20-35 were included in the study, with 329 in the low FEV1 group and 5017 in the normal group. The weighted prevalence of low FEV1 among young adults was 7.1% (95% CI 6.0 to 8.2). Low body mass index (OR=3.06, 95% CI 1.79 to 5.24), doctor-diagnosed asthma (OR=2.25, 1.28 to 3.93), and wheezing or whistling (OR=1.57, 1.06 to 2.33) were identified as independent risk factors for low FEV1. Over a 15-year follow-up, individuals in the low FEV1 group exhibited a higher likelihood of Medicaid use compared with those in the normal group (HR=1.73, 1.07 to 2.79). However, there was no statistically significant increase in the risk of all-cause mortality over a 30-year follow-up period (HR=1.48, 1.00 to 2.19). CONCLUSIONS: A considerable portion of young adults demonstrated low FEV1 levels, a characteristic that was associated with a higher risk of Medicaid use over a long-term follow-up, yet not linked to an augmented risk of all-cause mortality.