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Rationale: Moderate-severe obstructive sleep apnea (OSA) (apnea–hypopnea index [AHI], >15 events/h) disturbs sleep through frequent bouts of apnea and is associated with daytime sleepiness. However, many individuals without moderate-severe OSA (i.e., AHI <15 events/h) also report sleepiness. Objectives: To test the hypothesis that sleepiness in the AHI <15 events/h group is a consequence of substantial flow limitation in the absence of overt reductions in airflow (i.e., apnea/hypopnea). Methods: A total of 1,886 participants from the MESA sleep cohort were analyzed for frequency of flow limitation from polysomnogram-recorded nasal airflow signal. Excessive daytime sleepiness (EDS) was defined by an Epworth Sleepiness Scale score ⩾11. Covariate-adjusted logistic regression assessed the association between EDS (binary dependent variable) and frequency of flow limitation (continuous) in individuals with an AHI <15 events/h. Results: A total of 772 individuals with an AHI <15 events/h were included in the primary analysis. Flow limitation was associated with EDS (odds ratio, 2.04; 95% confidence interval, 1.17–3.54; per 2–standard deviation increase in flow limitation frequency) after adjusting for age, sex, body mass index, race/ethnicity, and sleep duration. This effect size did not appreciably change after also adjusting for AHI. Conclusions: In individuals with an AHI <15 events/h, increasing flow limitation frequency by 2 standard deviations is associated with a twofold increase in the risk of EDS. Future studies should investigate addressing flow limitation in low-AHI individuals as a potential mechanism for ameliorating sleepiness. [ABSTRACT FROM AUTHOR]

Background and Objective: The use of small airway parameters generated by spirometry, namely forced expiratory flow between 25% and 75% of forced vital capacity (FVC) (FEF25%–75%) and forced expiratory flow at 50% and 75% of FVC (FEF50% and FEF75%, respectively), is widely discussed. We evaluated the importance of these spirometric parameters in a large Chinese population. Methods: We conducted a cross‐sectional observational study in which spirometry and bronchodilator responsiveness (BDR) data were collected in a healthcare centre from May 2021 to August 2022 and in a tertiary hospital from January 2017 to March 2022. Discordance was assessed between the classification of test results by the large airway parameters of forced expiratory volume in 1 second (FEV1) and FEV1/FVC ratio and by the small airway parameters of FEF25%–75%, FEF75% and FEF50%. The predictive power of Z‐scores of spirometric parameters for airflow limitation and BDR was assessed using receiver operating characteristic curves. Results: Our study included 26,658 people. Among people with a normal FVC (n = 14,688), 3.7%, 4.5% and 3.6% of cases exhibited normal FEV1/FVC ratio but impaired FEF25%–75%, FEF75% and FEF50%, respectively, while 6.8%–7.0% of people exhibited normal FEV1 but impaired FEF25%–75%, FEF75% and FEF50%. Using the Z‐scores of combining both large and small airway parameters in spirometry showed the best area under the curve for predicting airflow limitation (0.90; 95% CI 0.87–0.94) and predicting BDR (0.72; 95% CI 0.71–0.73). Conclusion: It is important to consider both large and small airway parameters in spirometry to avoid missing a diagnosis of airflow obstruction. [ABSTRACT FROM AUTHOR]

Rationale: Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by airway obstruction and accelerated lung function decline. Our understanding of systemic protein biomarkers associated with COPD remains incomplete. Objectives: To determine what proteins and pathways are associated with impaired pulmonary function in a diverse population. Methods: We studied 6,722 participants across six cohort studies with both aptamer-based proteomic and spirometry data (4,566 predominantly White participants in a discovery analysis and 2,156 African American cohort participants in a validation). In linear regression models, we examined protein associations with baseline forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC). In linear mixed effects models, we investigated the associations of baseline protein levels with rate of FEV1 decline (ml/yr) in 2,777 participants with up to 7 years of follow-up spirometry. Results: We identified 254 proteins associated with FEV1 in our discovery analyses, with 80 proteins validated in the Jackson Heart Study. Novel validated protein associations include kallistatin serine protease inhibitor, growth differentiation factor 2, and tumor necrosis factor-like weak inducer of apoptosis (discovery β = 0.0561, Q = 4.05 × 10-10; β  = 0.0421, Q = 1.12 × 10-3; and β = 0.0358, Q = 1.67 × 10-3, respectively). In longitudinal analyses within cohorts with follow-up spirometry, we identified 15 proteins associated with FEV1 decline (Q

Xuefang Li,1 Zhijun Li,2 Jian Ye,2 Wu Ye2 1Department of Infectious Diseases, Zhejiang Hospital, Hangzhou, People’s Republic of China; 2Department of Respiratory Diseases, Zhejiang Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Wu Ye, Department of Respiratory Diseases, Zhejiang Hospital, 1229 Gudun Road, Xihu District, Hangzhou, Zhejiang Province, 310013, People’s Republic of China, Tel +86 15158100052, Email yewu55@126.comObjective: To determine the association of urinary phthalate metabolites with chronic obstructive pulmonary disease (COPD), airflow obstruction, lung function and respiratory symptoms.Methods: Our study included a total of 2023 individuals aged ≥ 40 years old in the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression was conducted to explore the correlation of eleven urinary phthalate metabolites (MCNP, MCOP, MECPP, MnBP, MCPP, MEP, MEHHP, MEHP, MiBP, MEOHP, and MBzP) with COPD, airflow obstruction and respiratory symptoms. Linear regression analyses were used to evaluate the relationship between urinary phthalate metabolites and lung function.Results: When compared to the first tertile, the third tertile of MEHHP was associated with the risk of COPD [OR: 2.779; 95% confidence interval (CI): 1.129– 6.840; P = 0.026]. Stratified analysis showed that MEHHP increased the risk of COPD by 7.080 times in male participants. Both MCPP and MBzP were positively correlated with the risk of airflow obstruction. The third tertile of MBzP increased the risk of cough by 1.545 (95% CI: 1.030– 2.317; P = 0.035) times. Both FEV1 and FVC were negatively associated with MEHHP, MECPP, MnBP, MEP, MiBP and MEOHP.Conclusion: Higher levels of MEHHP are associated with increased risk of COPD, and lower measures of FEV1 and FVC. MBzP is positively related to airflow obstruction and cough.Keywords: chronic obstructive pulmonary disease, phthalate, airflow obstruction, lung function, national health and nutrition examination survey

Yuka Koga,1 Sayaka Deguchi,1 Takeshi Matsuo,1 Akinori Suzuki,1 Gen Terashima,2 Takumi Tajima,2 Yoko Shibata,3 Hironori Sagara4 1Pharmaceutical Division, Pharmaceutical Company, Kracie, Ltd, Tokyo, Japan; 2Real World Evidence Division, JMDC Inc, Tokyo, Japan; 3Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan; 4Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, Tokyo, JapanCorrespondence: Yuka Koga, Pharmaceutical Division, Pharmaceutical Company, Kracie, Ltd, 3-20-20, Kaigan, Minato-ku, Tokyo, Japan, Tel +81 3-5446-3352, Fax +81 3-5446-3371, Email koga_yuka@kracie.co.jpPurpose: 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.Keywords: COPD, epidemiology, airflow obstruction, prevalence, Japan, real-world data

Background: Asthma in the elderly needs more attention in an aging society. However, it is likely to remain underdiagnosed and undertreated. This study aimed to clarify clinical characteristics of new-onset asthma in the elderly, describing the prevalence, predictive factors, and comorbidities after asthma diagnosis of new-onset asthma in the elderly in the general population. Methods: This community-based prospective cohort study enrolled 9804 generally healthy participants (30–74 years old) in Nagahama City, and conducted a follow-up assessment after 5 years. Elderly participants were those aged ≥65 years at baseline. Patients with new-onset asthma were defined as participants without asthma at baseline assessment and with asthma at the follow-up assessment. Results: Among the 7948 participants analyzed in this study, 28 (1.4%) elderly and 130 (2.2%) non-elderly had new-onset asthma. Multiple logistic regression analysis revealed low forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and high blood eosinophil counts at baseline as predicting factors for new-onset asthma in the elderly. Additionally, subsequent incidence of new-onset asthma was higher in elderly participants with both predictors (high blood eosinophil counts and low FEV1/FVC at baseline) than those with none or one of the predictors before asthma diagnosis. Lastly, elderly patients with new-onset asthma had more frequent comorbidity of moderate to severe sleep disordered breathing than those non-elderly. Conclusions: Eosinophilic inflammation and airflow obstruction may predict subsequent new-onset asthma after the age of 65 years. Revealing the characteristics of new-onset asthma in the elderly can aid in the prevention of underdiagnosed asthma.

Smaller mean airway tree caliber is associated with airflow obstruction and chronic obstructive pulmonary disease (COPD). We investigated whether airway tree caliber heterogeneity was associated with airflow obstruction and COPD. Two community-based cohorts (MESA Lung, CanCOLD) and a longitudinal case-control study of COPD (SPIROMICS) performed spirometry and computed tomography measurements of airway lumen diameters at standard anatomical locations (trachea-to-subsegments) and total lung volume. Percent-predicted airway lumen diameters were calculated using sex-specific reference equations accounting for age, height, and lung volume. The association of airway tree caliber heterogeneity, quantified as the standard deviation (SD) of percent-predicted airway lumen diameters, with baseline forced expired volume in 1-second (FEV1), FEV1/forced vital capacity (FEV1/FVC) and COPD, as well as longitudinal spirometry, were assessed using regression models adjusted for age, sex, height, race-ethnicity, and mean airway tree caliber. Among 2,505 MESA Lung participants (means ± SD age: 69 ± 9 yr; 53% female, mean airway tree caliber: 99 ± 10% predicted, airway tree caliber heterogeneity: 14 ± 5%; median follow-up: 6.1 yr), participants in the highest quartile of airway tree caliber heterogeneity exhibited lower FEV1 (adjusted mean difference: −125 mL, 95%CI: −171,−79), lower FEV1/FVC (adjusted mean difference: −0.01, 95%CI: −0.02,−0.01), and higher odds of COPD (adjusted odds ratio: 1.42, 95%CI: 1.01–2.02) when compared with the lowest quartile, whereas longitudinal changes in FEV1 and FEV1/FVC did not differ significantly. Observations in CanCOLD and SPIROMICS were consistent. Among older adults, airway tree caliber heterogeneity was associated with airflow obstruction and COPD at baseline but was not associated with longitudinal changes in spirometry. NEW & NOTEWORTHY: In this study, by leveraging two community-based samples and a case-control study of heavy smokers, we show that among older adults, airway tree caliber heterogeneity quantified by CT is associated with airflow obstruction and COPD independent of age, sex, height, race-ethnicity, and dysanapsis. These observations suggest that airway tree caliber heterogeneity is a structural trait associated with low baseline lung function and normal decline trajectory that is relevant to COPD. [ABSTRACT FROM AUTHOR]

Asthma in the elderly needs more attention in an aging society. However, it is likely to remain underdiagnosed and undertreated. This study aimed to clarify clinical characteristics of new-onset asthma in the elderly, describing the prevalence, predictive factors, and comorbidities after asthma diagnosis of new-onset asthma in the elderly in the general population. This community-based prospective cohort study enrolled 9804 generally healthy participants (30–74 years old) in Nagahama City, and conducted a follow-up assessment after 5 years. Elderly participants were those aged ≥65 years at baseline. Patients with new-onset asthma were defined as participants without asthma at baseline assessment and with asthma at the follow-up assessment. Among the 7948 participants analyzed in this study, 28 (1.4%) elderly and 130 (2.2%) non-elderly had new-onset asthma. Multiple logistic regression analysis revealed low forced expiratory volume in 1 s (FEV 1)/forced vital capacity (FVC) and high blood eosinophil counts at baseline as predicting factors for new-onset asthma in the elderly. Additionally, subsequent incidence of new-onset asthma was higher in elderly participants with both predictors (high blood eosinophil counts and low FEV 1 /FVC at baseline) than those with none or one of the predictors before asthma diagnosis. Lastly, elderly patients with new-onset asthma had more frequent comorbidity of moderate to severe sleep disordered breathing than those non-elderly. Eosinophilic inflammation and airflow obstruction may predict subsequent new-onset asthma after the age of 65 years. Revealing the characteristics of new-onset asthma in the elderly can aid in the prevention of underdiagnosed asthma. [ABSTRACT FROM AUTHOR]

Abstract Background Postoperative respiratory failure is the most frequent complication in postsurgical patients. The purpose of this study is to assess whether pulmonary function testing in high-risk patients during preoperative assessment detects previously unknown respiratory impairments which may influence patient outcomes. Methods A targeted patient screening by spirometry and the measurement of the diffusing capacity of the lung for carbon monoxide (DLCO) was implemented in the anesthesia department of a tertiary university hospital. Patients of all surgical disciplines who were at least 75 years old or exhibited reduced exercise tolerance with the metabolic equivalent of task less than four (MET

Background: During hot environment work tasks with whole-body enclosed anti-bioaerosol suit, the combined effect of heavy sweating and exhaled hot humid air may cause the N95 medical respirator to saturate with water/sweat (i.e., water-blocking). Methods: 32 young male subjects with different body mass indexes (BMI) in whole-body protection (N95 medical respirator + one-piece protective suit + head covering + protective face screen + gloves + shoe covers) were asked to simulate waste collecting from each isolated room in a seven-story building at 27-28°C, and the weight, inhalation resistance (Rf), and aerosol penetration of the respirator before worn and after water-blocking were analyzed. Results: All subjects reported water-blocking asphyxia of the N95 respirators within 36-67 min of the task. When water-blocking occurred, the Rf and 10-200 nm total aerosol penetration (Pt) of the respirators reached up to 1270-1810 Pa and 17.3-23.3%, respectively, which were 10 and 8 times of that before wearing. The most penetration particle size of the respirators increased from 49-65 nm before worn to 115-154 nm under water-blocking condition, and the corresponding maximum size-dependent aerosol penetration increased from 2.5-3.5% to 20-27%. With the increase of BMI, the water-blocking occurrence time firstly increased then reduced, while the Rf, Pt, and absorbed water all increased significantly. Conclusions: This study reveals respirator water-blocking and its serious negative impacts on respiratory protection. When performing moderate-to-high-load tasks with whole-body protection in a hot environment, it is recommended that respirator be replaced with a new one at least every hour to avoid water-blocking asphyxia.

Abstract Background Restrictive spirometry pattern (RSP), defined as reduced forced vital capacity (FVC) in absence of airflow obstruction (AFO), is associated with increased risk of mortality in general population. However, evidence in the patients with silicosis is limited. This study was aimed to investigate the relationship between RSP and the risk of death in a silicotic cohort. Method This retrospective cohort study used data from the Pneumoconiosis Clinic, Hong Kong Department of Health that containing 4315 patients aged 18–80 years and diagnosed with silicosis during 1981–2019, with a follow-up till 31 December 2019. Spirometry was carried out at the diagnostic examination of silicosis. Lung function categories were classified as normal spirometry (FEV1/FVC ≥ 0.7, FVC ≥ 80% predicted), RSP only (FEV1/FVC ≥ 0.7, FVC

Zhen-Yun Wu,1,&ast; Xiang-Min Lu,2,&ast; Rui Liu,1,&ast; Yan-Xia Han,3 Hong-Ying Qian,1 Qian Zhao,1 Mei’e Niu3 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2School of Nursing, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 3Department of Nursing, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei’e Niu, Department of Nursing, the First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Suzhou, Jiangsu, 215006, People’s Republic of China, Email meniu_123@163.com Qian Zhao, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, Jiangsu, 215006, People’s Republic of China, Email xujiali1983_01@163.comPurpose: This study was designed to investigate the differences in skeletal-muscle atrophy between patients with stable chronic obstructive pulmonary disease (COPD) and healthy controls; associated factors were also considered. The study comprised selected residents of communities near the First Affiliated Hospital of Soochow University in Suzhou City, East China.Patients and Methods: Included in this study were 123 COPD patients and 60 controls. All patients completed spirometry as well as examinations to determine their functional exercise capacity, body composition, and handgrip strength (HGS).Results: COPD patients had less fat-free mass (FFM), a lower FFM index (FFMI), and a lower 6-min walking distance (6MWD) compared with controls (P = 0.007, P = 0.020, and P < 0.001, respectively) (FFMI: 17.59 ± 1.83 vs 18.34 ± 1.64). The HGS of these patients was also lower compared with that of controls (32.88 ± 7.84 vs 35.48 ± 7.42), and HGS tended toward statistical significance (P = 0.064, respectively). In multivariate analysis, age (β = − 0.107, P < 0.001), gender (β = 0.212, P < 0.001), body mass index (BMI) (β = 0.462, P < 0.001), FEV1% (β = 0.108, P = 0.009), and calf circumference (CC) (β = 0.457, P < 0.001) were significantly associated with FFMI.Conclusion: Impaired skeletal muscle mass was more common in COPD patients than in controls. Multiple regression analysis showed that CC may be used to detect the degree of impairment, particularly by health-care providers working outside of the hospital.Keywords: airflow obstruction, calf circumference, chronic obstructive pulmonary disease, fat-free mass index, skeletal muscle atrophy, skeletal muscle mass

Rationale: Androgens are potentially beneficial in asthma, but AR (androgen receptor) has not been studied in human airways.Objectives: To measure whether AR and its ligands are associated with human asthma outcomes.Methods: We compared the effects of AR expression on lung function, symptom scores, and fractional exhaled nitric oxide (FeNO) in adults enrolled in SARP (Severe Asthma Research Program). The impact of sex and of androgens on asthma outcomes was also evaluated in the SARP with validation studies in the Cleveland Clinic Health System and the NHANES (U.S. National Health and Nutrition Examination Survey).Measurements and Main Results: In SARP (n = 128), AR gene expression from bronchoscopic epithelial brushings was positively associated with both FEV1/FVC ratio (R2 = 0.135, P = 0.0002) and the total Asthma Quality of Life Questionnaire score (R2 = 0.056, P = 0.016) and was negatively associated with FeNO (R2 = 0.178, P = 9.8 × 10-6) and NOS2 (nitric oxide synthase gene) expression (R2 = 0.281, P = 1.2 × 10-10). In SARP (n = 1,659), the Cleveland Clinic Health System (n = 32,527), and the NHANES (n = 2,629), women had more asthma exacerbations and emergency department visits than men. The levels of the AR ligand precursor dehydroepiandrosterone sulfate correlated positively with the FEV1 in both women and men.Conclusions: Higher bronchial AR expression and higher androgen levels are associated with better lung function, fewer symptoms, and a lower FeNO in human asthma. The role of androgens should be considered in asthma management.

Rogelio Perez-Padilla,1 Maria Montes de Oca,2 Ireri Thirion-Romero,1 Fernando C Wehrmeister,3 Maria Victorina Lopez,4 Gonzalo Valdivia,5 Jose R Jardim,6 Adriana Muino,4 Ana Maria B Menezes3 On behalf of the PLATINO Group1National Institute of Respiratory Diseases, Mexico City, Mexico; 2Pulmonary Division, Hospital Universitario de Caracas, Universidad Central de Venezuela, and Centro Medico de Caracas, Caracas, Venezuela; 3Post-Graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil; 4Universidad de la Republica. Hospital Maciel, Montevideo, Uruguay; 5Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; 6Paulista School of Medicine, Federal University of São Paulo, São Paulo, BrazilCorrespondence: Rogelio Perez-Padilla, Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, Col. Sección XVI, 14080, CDMX, Mexico City, Mexico, Email perezpad@gmail.comBackground: Preserved ratio impaired spirometry (PRISm) has been associated with adverse outcomes and increased transition to other spirometric categories over time. We aimed to examine its prevalence, trajectories over time, and outcomes in a population-based sample from Latin America.Methods: Data were obtained from two population-based surveys of adults from three cities in Latin America (PLATINO study), conducted on the same individuals 5– 9 years after their baseline examination. We estimated the frequency of PRISm defined by FEV1/FVC≥ 0.70 with FEV1 < 80%, describing their clinical characteristics, longitudinal transition trajectories over time, factors associated with the transition.Results: At baseline, 2942 participants completed post-bronchodilator spirometry, and 2026 at both evaluations. The prevalence of normal spirometry was 78%, GOLD-stage 1 10.6%, GOLD 2– 4 6.5%, and PRISm was: 5.0% (95% CI 4.2– 5.8). PRISm was associated with less schooling, more reports of physician-diagnosis of COPD, wheezing, dyspnea, missing days at work, having ≥ 2 exacerbations in the previous year but without accelerated lung function decline. Mortality risk was significantly higher in PRISm (HR 1.97, 95% CI 1.2– 3.3) and COPD GOLD 1– 4 categories (HR 1.79, 95% CI 1.3– 2.4) compared with normal spirometry. PRISm at baseline most frequently transitioned to another category at follow-up (46.5%); 26.7% to normal spirometry and 19.8% to COPD. The best predictors of transition to COPD were closeness of FEV1/FVC to 0.70, older age, current smoking, and a longer FET in the second assessment.Conclusion: PRISm, is a heterogeneous and unstable condition prone to adverse outcomes that require adequate follow-up.Keywords: preserved ratio impaired spirometry PRISm, airflow obstruction, COPD, lung function decline

Rationale: The diagnosis of chronic obstructive pulmonary disease (COPD) is based on a low FEV1/FVC ratio, but the severity of COPD is classified using FEV1% predicted (ppFEV1). Objectives: To test a new severity classification scheme for COPD using FEV1/FVC ratio, a more robust measure of airflow obstruction than ppFEV1. Methods: In COPDGene (Genetic Epidemiology of COPD) (N= 10,132), the severity of airflow obstruction was categorized by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1--4 (ppFEV1 of >80%, >50--80%, >30--50%, and,30%). A new severity classification (STaging of Airflow obstruction by Ratio; STAR) was tested in COPDGene--FEV1/ FVC >0.60 to,0.70, >0.50 to,0.60, >0.40 to,0.50, and,0.40, respectively, for stages 1--4--andappliedtothecombinedPittsburgh SCCOR and Emphysema COPD Research Registry for replication (N= 2,017). Measurements and Main Results: The agreements (weighted Bangdiwala B values) between GOLD and the new FEV1/FVC ratio severity stages were 0.89 in COPDGene and 0.88 in the Pittsburgh cohort. In COPDGene and the Pittsburgh cohort, compared with GOLD staging, STAR provided significant discrimination between the absence of airflow obstruction and stage 1 for all-cause mortality, respiratory quality of life, dyspnea, airway wall thickness, exacerbations, and lung function decline. No major differences were noted for emphysema, small airway disease, and 6-minute-walk distance. The STAR classification system identified a greater number of adults with stage 3/4 disease who would be eligible for lung transplantation and lung volume reduction procedure evaluations. Conclusions: The new STAR severity classification scheme provides discrimination for mortality that is similar to the GOLD classification but with a more uniform gradation of disease severity. STAR differentiates patients' symptoms, disease burden, and prognosis better than the existing scheme based on ppFEV1, and is less sensitive to race/ethnicity and other demographic characteristics. [ABSTRACT FROM AUTHOR]

Background: Restrictive spirometry pattern (RSP), defined as reduced forced vital capacity (FVC) in absence of airflow obstruction (AFO), is associated with increased risk of mortality in general population. However, evidence in the patients with silicosis is limited. This study was aimed to investigate the relationship between RSP and the risk of death in a silicotic cohort. Method: This retrospective cohort study used data from the Pneumoconiosis Clinic, Hong Kong Department of Health that containing 4315 patients aged 18–80 years and diagnosed with silicosis during 1981–2019, with a follow-up till 31 December 2019. Spirometry was carried out at the diagnostic examination of silicosis. Lung function categories were classified as normal spirometry (FEV1/FVC ≥ 0.7, FVC ≥ 80% predicted), RSP only (FEV1/FVC ≥ 0.7, FVC < 80% predicted), AFO only (FEV1/FVC < 0.7, FVC ≥ 80% predicted), and RSP&AFO mixed (FEV1/FVC < 0.7, FVC < 80% predicted). The hazard ratio (HR) and 95% confidence intervals (95% CI) were computed using a Cox proportional hazards model adjusting for age, body mass index, history of tuberculosis, smoking status, pack-years, and radiographic characteristics of silicotic nodules. Results: Among the 4315 patients enrolled in the study, the prevalence of RSP was 24.1% (n = 1038), including 11.0% (n = 473) with RSP only and 13.1% (n = 565) with mixed RSP and AFO. During the follow-up period, a total of 2399 (55.6%) deaths were observed. Compared with the silicotics with normal spirometry, those with RSP only had significantly increased risk of all-cause mortality (HR = 1.63, 95% CI 1.44–1.85) and respiratory-related mortality (HR = 1.56, 95% CI 1.31–1.85). Notably, a higher risk of mortality was observed in silicotics with mixed ventilatory defects of both RSP and AFO (all-cause mortality: HR = 2.22, 95% CI 1.95–2.52; respiratory-related mortality: HR = 2.59, 95% CI 2.18–3.07) than in those with RSP only. Conclusion: RSP is significantly associated with increased risk of all-cause and respiratory-related mortality in the silicotics, and patients with mixed restrictive and obstructive ventilatory defect have higher risk of mortality than those with single RSP or AFO. These findings emphasize the importance of recognizing RSP in the occupational settings, especially for the silicotic patients with mixed ventilatory defect. [ABSTRACT FROM AUTHOR]

Pulmonary tuberculosis (TB) is a well-known risk factor for airflow obstruction and chronic obstructive pulmonary disease (COPD). The prognosis of TB without sequelae on chest X-ray (CXR) remains uncertain. We used the 2008–2009 Korea National Health and Nutrition Examination Survey (KNHANES) data and 2007–2012 KNHANES-matched Health Insurance Review and Assessment Service cohort data. Airflow obstruction was assessed using a pulmonary function test. COPD was defined using diagnostic codes and the use of COPD medication for 3-year. We classified subjects into three groups based on TB history and sequelae on CXR. In 4911 subjects, the CXR(–) (no TB sequelae on CXR) post-TB group (n = 134) showed similar characteristics and normal lung function compared to that of the control group (n = 4,405), while the CXR(+) (TB sequelae on CXR) post-TB group (n = 372) showed different characteristics and reduced lung function. The prevalence of airflow obstruction was 9.3%, 13.4%, and 26.6% in control, CXR(-) post-TB, and CXR(+) post-TB groups, respectively. COPD was more common in the post-TB with CXR(+) (6.5%) or without CXR (–) (4.5%) groups, than in the control group (1.8%). Compared to the CXR(–) post-TB group, the control group showed a lower risk for airflow obstruction (OR, 0.774; p =.008). The CXR(+) post-TB group showed a higher risk for airflow obstruction (OR, 1.456; p =.011). The Control group also showed a lower risk for the development of COPD than the CXR(-) post-TB group (OR, 0.496; p =.011). We need to educate TB patients that airway obstruction and COPD can easily develop, even if TB sequelae are not observed on CXR. [ABSTRACT FROM AUTHOR]

Featured Application: Allele A of A3669G SNP was associated with steroid response to GCs in asthmatics. The heterozygous genotype of A3669G might be related to the type-2 allergic asthma phenotype. A3669G SNP can be used as a predictor of asthma severity and phenotype. Background: Glucocorticoids (GCs) represent the mainstay therapy for asthmatics. A subset of severe asthmatics fails to respond to steroid-based therapies, leading to important healthcare costs. Single nucleotide polymorphisms (SNPs) of glucocorticoid receptor genes were associated with a response to GC. We evaluate the possible relation of BclI and A3669G SNPs to clinical, biological and functional characteristics of asthmatics. Methods: We recruited 172 mild-to-severe asthmatic outpatients referring to the Severe Asthma and Rare Lung Disease Unit at San Luigi University Hospital. Clinical data were obtained at recruitment when spirometry tests and peripheral blood sampling were performed. Patients were genotyped for BclI and A3669G through the pyrosequencing assay results. Results: Patients with the A3669G AG genotype were younger, allergic and had higher IgE levels compared to AA genotype (p < 0.05). Moreover, asthmatics with the AA genotype had a lower post-bronchodilator FEV1/FVC ratio than the GG genotype (p < 0.05), and a higher RV/TLC ratio than the AG genotype (p < 0.05). Conclusions: The A3669G AG genotype might be related to type-2 allergic asthma; in particular, allele A of A3669G SNP was associated with GC response in our asthmatics. In conclusion, this observational cross-sectional study suggests a possible role of A3669G SNP as a predictor of asthma severity and phenotype. [ABSTRACT FROM AUTHOR]

Rationale: Currently used spirometry measures of airflow obstruction are influenced by demographics, predominantly by age, complicating selection of diagnostic thresholds for the presence of airflow obstruction. Objectives: To develop diagnostic thresholds for Parameter D, a new metric for detection of airflow obstruction, which quantifies the rate of rise of expiratory volume over time. Methods: We analyzed spirometry data of normal subjects enrolled in the 2007-2008, 2009-2010, and 2011-2012 NHANES (National Health and Nutrition Examination Survey) cohorts and calculated Parameter D using the expiratory volume-time curve. Relationships between demographics and lung function (forced expiratory volume in 1 second [FEV1], FEV1/forced vital capacity [FVC], and Parameter D) were tested using generalized linear models in NHANES and UK Biobank. The variation in lung function explained by demographics was estimated using R². A diagnostic threshold was developed for Parameter D using population-based percentiles. Based on concordance between the lower limit of normal (LLN) for FEV1/FVC and the Parameter D threshold, four groups were identified: normal (no airflow obstruction by either criterion), D1chronic obstructive pulmonary disease (D1COPD; positive by Parameter D only), D2COPD (positive by LLN only), and COPD (positive by both criteria), and associations with structural lung disease, exacerbations, and mortality were tested using multivariable analyses. Results: In contrast to FEV1 and FEV1/FVC, demographics cumulatively explained only 9% of the variance in Parameter D in NHANES (n = 4,945) and 3% in UK BioBank (n=109,623). In COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) (n = 9,542), a diagnostic threshold of 23.15 resulted in the identification of an additional 10.8% of participants with airflow obstruction. A total of 3.7% had FEV1/FVC,LLN but were missed by the Parameter D threshold. Compared with subjects in the normal group, after adjustment for age, sex, race, body mass index, pack-years of smoking, and current smoking status, D1COPD was associated with worse structural lung disease (odds ratio [OR] for >5% emphysema, 1.71; 95% confidence interval [CI], 1.37-2.12; OR for functional small airway disease>15%, 2.1; 95% CI, 1.79-2.67) and significant symptoms (OR for modified Medical Research Council dyspnea score>2, 1.25; 95% CI, 1.07-1.47; OR for St. George's respiratory questionnaire>25, 1.31; 95% CI, 1.13-1.53), a greater frequency of exacerbations (incidence rate ratio, 1.26; 95% CI, 1.10-1.46), and higher mortality (hazard ratio, 1.32; 95% CI, 1.10-1.57). Over 5 years, 28% of the D1COPD group versus 8% of normal group progressed to COPD by traditional criteria. Conclusions: Parameter D is not affected by age, and a normal population-based diagnostic threshold results in the early identification of additional individuals with airflow obstruction with a substantial amount of structural lung disease and respiratory symptoms. [ABSTRACT FROM AUTHOR]

BackgroundPulmonary tuberculosis (PTB) is associated with many forms of chronic lung disease including the development of chronic airflow obstruction (AFO). However, the nature, evolution and mechanisms responsible for the AFO after PTB are poorly understood. The aim of this study was to examine the progression of changes in lung physiology in patients treated for PTB.MethodsImmunocompetent, previously healthy, adult patients receiving ambulatory treatment for a first episode of tuberculosis were prospectively followed up with serial lung physiology and quantitative computed tomography (CT) lung scans performed at diagnosis of tuberculosis, 2, 6, 12 and 18 months during and after the completion of treatment.ResultsForty-nine patients (median age 26 years; 37.2% males) were included, and 43 were studied. During treatment, lung volumes improved and CT fibrosis scores decreased, but features of AFO and gas trapping emerged, while reduced diffusing capacity (DLco) seen in a majority of patients persisted. Significant increases in total lung capacity (TLC) by plethysmography were seen in the year following treatment completion (median change 5.9% pred., P45%), and 78.6% had reduced DLco.ConclusionSimple spirometry alone does not fully reveal the residual respiratory impairments resulting after a first episode of PTB. Changes in physiology evolve after treatment completion, and these findings when taken together, suggest emergence of gas trapping after treatment likely caused by progression of small airway pathology during the healing process.

This study aimed to explore the relationship between body mass index (BMI) and abdominal obesity and the risk of airflow obstruction, based on the data from the 2007–2012 National Health and Nutrition Survey (NHANES). Logistic regression was applied to assess the relationships between BMI or abdominal obesity and the risk of airflow obstruction by the fixed ratio method and the lower limit of normal (LLN) method. We further used the restricted cubic splines with 3 knots located at the 5th, 50th, and 95th percentiles of the distribution to evaluate the dose-response relationship. A total of 12,865 individuals aged 20–80 years old were included. In the fixed ratio method, underweight was positively correlated with the risk of airflow obstruction, and overweight and obesity were negatively correlated with the risk of airflow obstruction. In the LLN method, the results were consistent with the fixed ratio method. Abdominal obesity was positively associated with the risk of airflow obstruction only in the fixed ratio method (OR: 1.41, 95% CI: 1.04–1.90). There was an additive interaction between underweight and smoking on airflow obstruction in both methods. Abdominal obesity and smoking had additive interactions in the LLN method. Dose-response analysis indicated that there was a non-linear trend between BMI and the risk of airflow obstruction (Pfor nonlinearity < 0.01). Our study suggested that underweight and abdominal obesity were associated with the increased risk of airflow obstruction, and overweight and general obesity were associated with the decreased risk of airflow obstruction.

Introduction: The ideal contrast agents for ventilation SPECT and MRI are Technegas and 129Xe gas, respectively. Despite increasing interest in the clinical utility of ventilation imaging, these modalities have not been directly compared. Therefore, our objective was to compare the ventilation defect percent (VDP) assessed by Technegas SPECT and hyperpolarized 129Xe MRI in patients scheduled to undergo lung cancer resection with and without pre-existing obstructive lung disease. Methods: Forty-one adults scheduled to undergo lung cancer resection performed same-day Technegas SPECT, hyperpolarized 129Xe MRI, spirometry, and diffusing capacity of the lung for carbon monoxide (DLCO). Ventilation abnormalities were quantified as the VDP using two different methods: adaptive thresholding (VDPT) and k-means clustering (VDPK). Correlation and agreement between VDP quantified by Technegas SPECT and 129Xe MRI were determined by Spearman correlation and Bland-Altman analysis, respectively. Results: VDP measured by Technegas SPECT and 129Xe MRI were correlated (VDPT: r = 0.48, p = 0.001; VDPK: r = 0.63, p < 0.0001). A 2.0% and 1.6% bias towards higher Technegas SPECT VDP was measured using the adaptive threshold method (VDPT: 23.0% ± 14.0% vs. 21.0% ± 5.2%, p = 0.81) and k-means method (VDPK: 9.4% ± 9.4% vs. 7.8% ± 10.0%, p = 0.02), respectively. For both modalities, higher VDP was correlated with lower FEV1/FVC (SPECT VDPT: r = -0.38, p = 0.01; MRI VDPK: r=-0.46, p = 0.002) and DLCO (SPECT VDPT: r=-0.61, p < 0.0001; MRI VDPK: r = -0.68, p < 0.0001). Subgroup analysis revealed that VDP measured by both modalities was significantly higher for participants with COPD (n = 13) than those with asthma (n = 6; SPECT VDPT: p = 0.007, MRI VDPK: p = 0.006) and those with no history of obstructive lung disease (n = 21; SPECT VDPT: p = 0.0003, MRI VDPK: p = 0.0003). Discussion: The burden of ventilation defects quantified by Technegas SPECT and 129Xe MRI VDP was correlated and greater in participants with COPD when compared to those without. Our observations indicate that, despite substantial differences between the imaging modalities, quantitative assessment of ventilation defects by Technegas SPECT and 129Xe MRI is comparable. [ABSTRACT FROM AUTHOR]

Rationale: A positive bronchodilator response (BDR) according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines require both 200 ml and 12% increase in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) after bronchodilator inhalation. This dual criterion is insensitive in those with high or low FEV1.Objectives: To establish BDR criteria with volume or percentage FEV1 change.Methods: The largest FEV1 and FVC were identified from three pre- and three post-bronchodilator maneuvers in COPDGene (Genetic Epidemiology of COPD) participants. A total of 7,741 individuals with coefficient of variation less than 15% for both FEV1 and FVC formed bronchodilator categories of FEV1 response: negative (≤0.00% or ≤0.00 L), minimal (>0.00% to ≤9.00% or >0.00 L to ≤0.09 L), mild (>9.00% to ≤16.00% or >0.09 L to ≤0.16 L), moderate (>16.00% to ≤26.00% or >0.16 L to ≤0.26 L), and marked (>26.00% or >0.26 L). These response size categories are based on empirical limits considering average FEV1 increase of approximately 160 ml and the clinically important difference for FEV1. To compare flow and volume response characteristics, BDR-FEV1 category assignments were applied for the BDR-FVC response.Results: Twenty percent met mild and 31% met moderate or marked BDR-FEV1 criteria, whereas 12% met mild and 33% met moderate or marked BDR-FVC criteria. In contrast, only 20.6% met ATS/ERS positive criteria. Compared with the negative BDR-FEV1 category, the minimal, mild, moderate, and marked BDR-FEV1 categories were associated with greater 6-minute-walk distance and lower St. George's Respiratory Questionnaire and modified Medical Research Council dyspnea scale scores. Compared with negative BDR, moderate and marked BDR-FEV1 categories were associated with fewer exacerbations, and minimal BDR was associated with lower computed tomography airway wall thickness. Compared with the negative category, all BDR-FVC categories were associated with increasing emphysema percentage and gas trapping percentage. Moderate and marked BDR-FVC categories were associated with higher St. George's Respiratory Questionnaire scores but fewer exacerbations and lower dyspnea scores.Conclusions: BDR grading by FEV1 volume or percentage response identified subjects otherwise missed by ATS/ERS criteria. BDR grades were associated with functional exercise performance, quality of life, exacerbation frequency, dyspnea, and radiological airway measures. BDR grades in FEV1 and FVC indicate different clinical and radiological characteristics.

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation. Spirometry loops are not smooth curves and have undulations and peaks that likely reflect heterogeneity of airflow.Objectives: To assess whether the Peak Index, the number of peaks adjusted for lung size, is associated with clinical outcomes.Methods: We analyzed spirometry data of 9,584 participants enrolled in the COPDGene study and counted the number of peaks in the descending part of the expiratory flow-volume curve from the peak expiratory flow to end-expiration. We adjusted the peaks count for the volume of the lungs from peak expiratory flow to end-expiration to derive the Peak Index. Multivariable regression analyses were performed to test associations between the Peak Index and lung function, respiratory morbidity, structural lung disease on computed tomography (CT), forced expiratory volume in 1 second (FEV1) decline, and mortality.Results: The Peak Index progressively increased from Global Initiative for Chronic Obstructive Lung Disease stage 0 through 4 (P

Introduction: The ideal contrast agents for ventilation SPECT and MRI are Technegas and 129Xe gas, respectively. Despite increasing interest in the clinical utility of ventilation imaging, these modalities have not been directly compared. Therefore, our objective was to compare the ventilation defect percent (VDP) assessed by Technegas SPECT and hyperpolarized 129Xe MRI in patients scheduled to undergo lung cancer resection with and without pre-existing obstructive lung disease.Methods: Forty-one adults scheduled to undergo lung cancer resection performed same-day Technegas SPECT, hyperpolarized 129Xe MRI, spirometry, and diffusing capacity of the lung for carbon monoxide (DLCO). Ventilation abnormalities were quantified as the VDP using two different methods: adaptive thresholding (VDPT) and k-means clustering (VDPK). Correlation and agreement between VDP quantified by Technegas SPECT and 129Xe MRI were determined by Spearman correlation and Bland-Altman analysis, respectively.Results: VDP measured by Technegas SPECT and 129Xe MRI were correlated (VDPT: r = 0.48, p = 0.001; VDPK: r = 0.63, p < 0.0001). A 2.0% and 1.6% bias towards higher Technegas SPECT VDP was measured using the adaptive threshold method (VDPT: 23.0% ± 14.0% vs. 21.0% ± 5.2%, p = 0.81) and k-means method (VDPK: 9.4% ± 9.4% vs. 7.8% ± 10.0%, p = 0.02), respectively. For both modalities, higher VDP was correlated with lower FEV1/FVC (SPECT VDPT: r = −0.38, p = 0.01; MRI VDPK: r = −0.46, p = 0.002) and DLCO (SPECT VDPT: r = −0.61, p < 0.0001; MRI VDPK: r = −0.68, p < 0.0001). Subgroup analysis revealed that VDP measured by both modalities was significantly higher for participants with COPD (n = 13) than those with asthma (n = 6; SPECT VDPT: p = 0.007, MRI VDPK: p = 0.006) and those with no history of obstructive lung disease (n = 21; SPECT VDPT: p = 0.0003, MRI VDPK: p = 0.0003).Discussion: The burden of ventilation defects quantified by Technegas SPECT and 129Xe MRI VDP was correlated and greater in participants with COPD when compared to those without. Our observations indicate that, despite substantial differences between the imaging modalities, quantitative assessment of ventilation defects by Technegas SPECT and 129Xe MRI is comparable.

Abstract Background There is increasing evidence of small airway abnormalities in smokers despite normal spirometry. The concavity in the descending limb of the maximum expiratory flow curve (MEFV) is a recognised feature of obstruction and can provide information beyond FEV1, and potentially early smoking-related damage. We aimed to evaluate concavity measures compared to known small airway measurements. Methods Eighty smokers with normal spirometry had small airway function assessed: multiple breath nitrogen washout (MBNW) from which ventilation heterogeneity in the diffusion-dependent acinar (Sacin) and convection-dependent conductive (Scond) airways were assessed, and impulse oscillometry system (IOS) from which respiratory resistance and reactance at 5 Hz (R5 and X5) were measured. Concavity measures were calculated from the MEFV, partitioned into global and peripheral concavity. Results We found abnormal peripheral and global concavity as well as acinar ventilation heterogeneity are common in “normal” smokers. Concavity measures were not related to either MBNW or IOS measurements. Conclusion Abnormalities in concavity indices and MBNW or oscillometry parameters are common in smokers despite normal spirometry. However, these measures likely reflect different mechanisms of peripheral airway dysfunction.

Yao-Kuang Wu,1,2 Wen-Lin Su,1,2 Mei-Chen Yang,1,2 Sin-Yi Chen,1 Chih-Wei Wu,1 Chou-Chin Lan1,2 1Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 2School of Medicine, Tzu-Chi University, Hualien, TaiwanCorrespondence: Chou-Chin Lan, Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289, Jianguo Road, Xindian Dist., New Taipei City, Taiwan, Tel +886-2-66289779 ext 5709, Fax +886-2-66289009, Email bluescopy@yahoo.com.twBackground: Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease with an increased mortality rate in recent years, mainly caused by exposure to tobacco smoke. Regular physical activity is thought to diminish the risk of COPD exacerbation, while very few studies investigate the interaction between smoking and physical activity on COPD development. This study aims to investigate the association between smoking status, physical activity and prevalent COPD.Methods: This study analyzed data of adults 20 to 79 years old from the National Health and Nutrition Examination Survey (NHANES) 2007– 2012.Results: A total of 6404 participants aged 20– 79 were included and divided into four groups by their physical activity levels and smoking status. Amongst, 2819 (43.7%) were physically active non-smokers, 957 (14.8%) were physically inactive non-smokers, 1952 (30.3%) were physically active smokers, and 717 (11.1%) were physically inactive smokers. Prevalence of airflow obstruction were 5.7%, 7.1%, 17.7% and 18.6%, respectively. After adjustment, physically active smokers (aOR=2.71, 95% CI=1.94– 3.80) and physically inactive smokers (aOR=2.70, 95% CI=1.78– 4.09) but not physically active non-smokers were more likely to have airflow obstruction than physically active non-smokers. These associations were similar among most subgroups by age, sex, or BMI. Among smokers, being physically inactive was not significantly associated with a greater chance for prevalent airflow obstruction than being physically active.Conclusion: Smokers, regardless of their physical activity level, are more likely to have airflow obstruction as compared with physically active non-smokers. Within smokers, being physically inactive poses no excess chance to be airflow obstructed. The findings indicate that physical activity level seem not altering the relationship between smoking and airflow obstruction.Keywords: chronic obstructive pulmonary disease, smoking, physical activity, airflow obstruction

Context: Chronic obstructive pulmonary disease (COPD) is a widespread reason of disease and death in developing countries like India, although it is preventable, controllable, and treatable. Objectives: We studied the occurrence of metabolic syndrome (MetS) among cases of stable COPD and determined the correlation between stable COPD with MetS and body mass index, airflow obstruction, dyspnea, and exercise (BODE index) and C-reactive protein (CRP) titer. Methods: The study was a case–control analysis conducted on 90 patients from November 2019 to August 2020. Results: Seventy percentage of our case population belonged to Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade 1 and 2. A significant correlation between forced expiratory volume 1 s (FEV1) with body mass index (BMI), triglycerides (TGs), high-density lipoproteins (HDL), systolic blood pressure (SBP), and fasting blood sugar (FBS) was found. The higher the GOLD grade (lower FEV1), the higher the values of BMI, TG, HDL, SBP, and FBS. A negative association with MetS is related to small study population. Conclusion: Patients with MetS had significantly lower FEV1, higher mean SI, higher mean waist circumference, higher mean BMI, higher mean SBP and diastolic blood pressure, higher FBS, and higher HDL and TG. Patients with MetS showed higher BODE index and CRP titer compared to ones without it. Apart from routine vaccination, assessment of systemic comorbidities for early detection of MetS plays a pivotal role to provide best possible quality of life and utmost care to COPD patients and helps reduce mortality and morbidities of COPD.

BackgroundAirflow obstruction is a critical element of chronic airway diseases. This study aimed to evaluate the impact of preoperative airflow obstruction on the prognosis of patients following surgery for esophageal carcinoma.MethodsA total of 821 esophageal cancer patients were included and classified into two groups based on whether or not they had preoperative airflow obstruction. Airflow obstruction was defined as a forced expiration volume in the first second (FEV1)/forced vital capacity (FVC) ratio below the lower limit of normal (LLN). A retrospective analysis of the impact of airflow obstruction on the survival of patients with esophageal carcinoma undergoing esophagectomy was performed.ResultsPatients with airflow obstruction (102/821, 12.4%) had lower three-year overall (42/102, 58.8%) and progression-free survival rate (47/102, 53.9%) than those without airflow obstruction (P

IntroductionExposure to secondhand smoke (SHS) is associated with occult obstructive lung disease as evident by abnormal airflow indices representing small airway disease despite having preserved spirometry (normal forced expiratory volume in 1 s-to-forced vital capacity ratio, FEV1/FVC). The significance of lung volumes that reflect air trapping in the presence of preserved spirometry is unclear.MethodsTo investigate whether lung volumes representing air trapping could determine susceptibility to respiratory morbidity in people with SHS exposure but without spirometric chronic obstructive pulmonary disease, we examined a cohort of 256 subjects with prolonged occupational SHS exposure and preserved spirometry. We elicited symptom prevalence by structured questionnaires, examined functional capacity (maximum oxygen uptake, VO2max) by exercise testing, and estimated associations of those outcomes with air trapping (plethysmography-measured residual volume-to-total lung capacity ratio, RV/TLC), and progressive air trapping with exertion (increase in fraction of tidal breathing that is flow limited on expiration during exercise (per cent of expiratory flow limitation, %EFL)).ResultsRV/TLC was within the predicted normal limits, but was highly variable spanning 22%±13% and 16%±8% across the increments of FEV1/FVC and FEV1, respectively. Respiratory complaints were prevalent (50.4%) with the most common symptom being ≥2 episodes of cough per year (44.5%). Higher RV/TLC was associated with higher OR of reporting respiratory symptoms (n=256; r2=0.03; p=0.011) and lower VO2max (n=179; r2=0.47; p=0.013), and %EFL was negatively associated with VO2max (n=32; r2=0.40; p=0.017).ConclusionsIn those at risk for obstruction due to SHS exposure but with preserved spirometry, higher RV/TLC identifies a subgroup with increased respiratory symptoms and lower exercise capacity.

Objective: Farmers have an increased risk for chronic bronchitis and airflow obstruction. The objective of this study was to investigate the association of these health outcomes with farm activities. Methods: We evaluated the Keokuk County Rural Health Study (KCRHS) enrollment data for farm activities and the two health outcomes chronic bronchitis based on self-reported symptoms and airflow obstruction based on spirometry. We used logistic regression to model the health outcomes, yielding an odds ratio (OR) and 95% confidence interval (95% CI) for farm activities while adjusting for potential confounders and other risk factors. Results: Of the 1234 farmers, 104 (8.4%) had chronic bronchitis, 75 (6.1%) fulfilled the criteria for airflow obstruction, and the two outcomes overlapped by 18 participants. Chronic bronchitis without airflow obstruction (n = 86) had a statistically significant association with crop storage insecticides (OR 3.1, 95% CI 1.6, 6.1) and a low number of years (≤ 3) worked with turkeys (OR 3.3, 95% CI 1.2, 9.4). The latter result should be interpreted with caution because it is based on a small number of cases (n = 5). Airflow obstruction with or without chronic bronchitis (n = 75) was significantly associated with ever working in a hog or chicken confinement setting (OR 2.2, 95% CI 1.0, 4.5). Conclusions: These results suggest that work with crop storage insecticides or turkeys may increase the risk for chronic bronchitis and work in hog or chicken confinement may increase the risk for airflow obstruction. [ABSTRACT FROM AUTHOR]

Background: Whether the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV 1 /FVC) can be used as a biomarker to predict the risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is unclear., Methods: To investigate the predictive role of FEV 1 /FVC for AECOPD, we analyzed data from an observational and multicenter cohort study of 2043 patients with COPD in KOREA. Exposures were post-bronchodilator FEV 1 /FVC and/or percentage predicted FEV 1 (FEV 1 %pred). The outcome was the development of AECOPD during the first year of follow-up., Results: During the first year of follow-up, the proportion of patients who developed AECOPD increased as FEV 1 /FVC decreased (P < 0.01). FEV 1 /FVC and FEV 1 %pred had similar predictive power for AECOPD, with optimal predictive cut-offs of approximately 0.5 for FEV 1 /FVC and 50 % for FEV 1 %pred. When the participants were classified into groups based on these cut-offs, compared with a high both-lung function group (FEV 1 /FVC≥0.5 and FEV 1 %pred≥50 %), the low-FEV 1 group (FEV 1 /FVC≥0.5 and FEV 1 %pred<50) had a modestly increased risk of severe AECOPD (adjusted odds ratio[aOR] = 3.12; 95 % confidence interval[CI] = 1.59-6.16), while the risk of severe AECOPD was the highest in the low both-lung function group (FEV 1 %pred<50 % and FEV 1 /FVC<0.5) (aOR = 5.16; 95 % CI = 3.34-7.97)., Conclusions: FEV 1 /FVC is a spirometric biomarker predictive of AECOPD. In countries where FEV 1 %pred is not available for their population, FEV 1 /FVC could be used as a biomarker for assessing the risk of AECOPD. In countries where accurate FEV 1 %pred is available, both FEV 1 %pred and FEV 1 /FVC could be used to provide additional information to assess the risk of AECOPD., Key Message: This study showed that FEV 1 /FVC had similar predictive power for AECOPD compared with percentage predicted FEV 1 . Furthermore, the use of both FEV 1 and FEV 1 /FVC provides additional information for the risk assessment of AECOPD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objectives: Different factors (etiotypes) can lead to persistent airflow obstruction (PAO) across the lifetime, including genetic factors, abnormal lung development, cigarette smoking, traffic pollution exposure, respiratory infections and asthma. Here we explore the prevalence of PAO and associated etiotypes in the general population in different age bins., Methods: We studied 664 individuals with PAO (FEV1/FVC post bronchodilation (post-BD) below the lower limit of normal (LLN)) and 11,522 with normal lung function (FEV1/FVC, FEV1 and FVC ≥ LLN and ≤ upper limit of normal (ULN) post-BD) included in the LEAD Study (NCT01727518), a general population cohort in Vienna (Austria). For analysis, participants were stratified in three age bins (<25, 25-<50 and ≥ 50 years of age)., Results: PAO occurred in 3.8 % in females and 5.6 % in males of the cohort, and it increased with age. Most participants with PAO (57.5 %) reported respiratory symptoms, indicating a high burden of disease. PAO was associated with male sex (25-<50 years), ever smoking (>50 years), increased number of pack years (25-<50 years, >50 years), not being breastfed (<25 years) and ever diagnosis of asthma (in all age bins). Etiotypes varied by age bins with cigarette smoking being the most prevalent one, often in combination with traffic pollution exposure., Conclusion: In the general population PAO occurs in about 5 % of participants with a higher prevalence in older individuals. Etiotypes and associated factors for PAO accumulate with age., Competing Interests: Declaration of competing interest Grasl M.T. has, within the last 3 years, received an unrestricted Grant for The Ludwig Boltzmann Institute for Lung Health for this study; support for attending meetings by Vivisol, Habel and AstraZeneca. She is a member of advisory boards for Boehringer Ingelheim.Agusti A. is a chairman of the Board of directors of GOLD. He received grants from AstraZeneca, GSK and Menarini. He received honoraria for lectures and presentations from AstraZeneca, GSK, Chiesi, Menarini, Sanofi and Zambon.Hartl S. received honoraria for lectures and presentations from AstraZeneca and GSK. She is a member of advisory boards for AstraZeneca, GSK and Menarini. She also received unrestricted scientific grants from AstraZeneca, GSK and Menarini Pharma for the Austrian LEAD Study.Breyer-Kohansal R. received consulting fees AstraZeneca, Boehringer Ingelheim, Glaxo Smith Kline, Menarini, Novartis Pharma and Sanofi. She is a member of advisory boards for AstraZeneca, Sanofi and Menarini.Karimi A., Breyer M.-K. and Azizzadeh M. have no declaration of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Alongside the recognized Global Initiative for Obstructive Lung Disease (GOLD) classification, the Staging of Airflow Obstruction by Ratio (STAR) severity scheme has been proposed for categorizing COPD., Study Question: What are the agreement and utility of the GOLD and STAR classifications in patients with severe COPD entering the rehabilitation setting?, Study Design and Methods: Medical records were reviewed in this multicenter retrospective study, examining key functional variables and their changes in a large cohort of patients with COPD undergoing pulmonary rehabilitation., Results: A total of 1,516 participants (33.7% female participants; median age, 72.0 years) were included in the analysis. Compared with GOLD, the use of the STAR classification resulted in a different disease severity category for 53.4% of patients. An unweighted Cohen's kappa of 0.25 and a Bangdiwala B value of 0.24 indicated a fair agreement between the 2 classifications. Higher weighted agreement measures (0.47 and 0.78, respectively) suggested that discrepancies between the classifications mainly occurred for contiguous stages. GOLD exhibited superior discrimination between stages for chronic respiratory failure, whereas STAR exhibited better performance in detecting hyperinflation. In terms of their application within pulmonary rehabilitation settings, GOLD exhibited superior performance compared with STAR in identifying the minimal clinically important difference in 6-minute walking distance and modified Medical Research Council score. Accordingly, GOLD but not STAR acted as an independent predictor for achieving a minimal clinically important difference in modified Medical Research Council score (OR, 1.48; 95% CI, 1.12-1.94; P = .005) and also independently predicted changes in the Braden scale score (β = 0.154; P = .004)., Interpretation: STAR exhibits a more uniform gradation of disease severity and enhanced performance in detecting hyperinflation, but our preliminary findings do not endorse its utilization in the rehabilitation setting., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: M. V. reports grants from Chiesi, MedicAir, and Vivisol; and lecture honoraria from GlaxoSmithKline, AstraZeneca, Chiesi, Menarini, Lusofarmaco and MedicAir, outside the submitted work. G. M. Is the recipient of a grant from Piano Nazionale di Ripresa e Resilienza/Missione 6 (PNRR/M6). A.S. reports lecture honoraria, travel support, and advisory board participation with Chiesi, AstraZeneca, GlaxoSmithKline, Lusofarmaco, Menarini, Sanofi, and MSD, outside the submitted work. M. M. reports grants or contracts (with payments to Istituti Clinici Scientifici Maugeri IRCCS) from GlaxoSmithKline and AstraZeneca, and payments or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from GlaxoSmithKline, AstraZeneca, and Chiesi, outside the submitted work. None disclosed: (P. A., N. A.)., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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Purpose: To identify plasma alterations in lipid species in patients with chronic obstructive pulmonary disease (COPD), as well as, relationships with smoking status, oxidative and inflammatory markers. Methods: Plasma was obtained from 100 patients with COPD and 120 healthy controls. Pulmonary function was assessed by plethysmography. Serum levels of IL-6 and TNF-α were determined by ELISA. Oxidative stress parameters were measured using standard methods. Lipids were extracted then analyzed by Matrix-Assisted Laser Desorption and Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-TOF-MS). Results: More than 40 lipid compounds were identified within plasma samples. Among these 19 lipid species including plasmalogens (PC O-), phosphatidylcholines (PC), and triglycerides (TG) were significantly altered in COPD. A decreased expression of PC O- (36:1, 36:2, 36:3, 36:4, 38:4, 38:5) species was found in patients with different severities compared to healthy controls. There was also a decrease in PC (34:3, 36:0, 36:4, 36:5, 40:6, 40:7) species in COPD patients. PC (34:3) levels were positively correlated with disease progression and pulmonary function decline (forced expiratory volume in 1 s (FEV1)) (r = 0.84, p < 0.001) and inversely correlated with thiobarbituric acid-reactive substances (TBARS) (r = − 0.77, p < 0.001). TG (50:0, 50:1, 52:1, 52:2, 52:3, 52:4, 54:4) species were altered in COPD patients and in those with advanced disease stages. Significant correlations between FEV1, TBARS, peroxynitrite, and TG (52:3) were found among COPD patients (r = − 0.69; r = 0.86; r = 0.77, p < 0.001, respectively). Conclusion: PC (34:3) and TG (52:3) could be potential lipid signatures of COPD that correlate with altered pulmonary function and oxidative status. [ABSTRACT FROM AUTHOR]

Rationale: Early detection of chronic obstructive pulmonary disease (COPD) is a public health priority. Airflow obstruction is the single most important risk factor for adverse COPD outcomes, but spirometry is not routinely recommended for screening. Objectives: To describe the burden of subclinical airflow obstruction (SAO) and to develop a probability score for SAO to inform potential detection and prevention programs. Methods: Lung function and clinical data were harmonized and pooled across nine U.S. general population cohorts. Adults with respiratory symptoms, inhaler use, or prior diagnosis of COPD or asthma were excluded. A probability score for prevalent SAO (forced expiratory volume in 1 second/forced vital capacity < 0.70) was developed via hierarchical group-lasso regularization from clinical variables in strata of sex and smoking status, and its discriminative accuracy for SAO was assessed in the pooled cohort as well as in an external validation cohort (NHANES [National Health and Nutrition Examination Survey] 2011-2012). Incident hospitalizations and deaths due to COPD (respiratory events) were defined by adjudication or administrative criteria in four of nine cohorts. Results: Of 33,546 participants (mean age 52 yr, 54% female, 44% non-Hispanic White), 4,424 (13.2%) had prevalent SAO. The incidence of respiratory events (Nat-risk = 14,024) was threefold higher in participants with SAO versus those without (152 vs. 39 events/10,000 person-years). The probability score, which was based on six commonly available variables (age, sex, race and/or ethnicity, body mass index, smoking status, and smoking pack-years) was well calibrated and showed excellent discrimination in both the testing sample (C-statistic, 0.81; 95% confidence interval [CI], 0.80-0.82) and in NHANES (C-statistic, 0.83; 95% CI, 0.80-0.86). Among participants with predicted probabilities ⩾ 15%, 3.2 would need to undergo spirometry to detect one case of SAO. Conclusions: Adults with SAO demonstrate excess respiratory hospitalization and mortality. A probability score for SAO using commonly available clinical risk factors may be suitable for targeting screening and primary prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoids (GCs) represent the mainstay therapy for asthmatics. A subset of severe asthmatics fails to respond to steroid-based therapies, leading to important healthcare costs. Single nucleotide polymorphisms (SNPs) of glucocorticoid receptor genes were associated with a response to GC. We evaluate the possible relation of BclI and A3669G SNPs to clinical, biological and functional characteristics of asthmatics. Methods: We recruited 172 mild-to-severe asthmatic outpatients referring to the Severe Asthma and Rare Lung Disease Unit at San Luigi University Hospital. Clinical data were obtained at recruitment when spirometry tests and peripheral blood sampling were performed. Patients were genotyped for BclI and A3669G through the pyrosequencing assay results. Results: Patients with the A3669G AG genotype were younger, allergic and had higher IgE levels compared to AA genotype (p < 0.05). Moreover, asthmatics with the AA genotype had a lower post-bronchodilator FEV1/FVC ratio than the GG genotype (p < 0.05), and a higher RV/TLC ratio than the AG genotype (p < 0.05). Conclusions: The A3669G AG genotype might be related to type-2 allergic asthma; in particular, allele A of A3669G SNP was associated with GC response in our asthmatics. In conclusion, this observational cross-sectional study suggests a possible role of A3669G SNP as a predictor of asthma severity and phenotype.

Pulmonary function is associated with the development of chronic liver disease. However, evidence of the association between pulmonary function and cirrhosis risk is still lacking. This study aimed to investigate the longitudinal associations of pulmonary function with the development of cirrhosis, and to explore whether genetic predisposition to cirrhosis could modify these associations. Of 294,835 participants free of cirrhosis and had undergone spirometry at baseline from the UK Biobank were included. Cirrhosis diagnoses were ascertained through linked hospital records and death registries. Cox proportional hazard models were employed to investigate the longitudinal associations between pulmonary function, genetic predisposition, and cirrhosis risk. During a median follow-up of 12.0 years, 2598 incident cirrhosis cases were documented. Compared to individuals with normal spirometry findings, those with preserved ratio impaired spirometry (PRISm) findings (hazard ratio [HR] and 95% confidence interval [CI]: 1.32 [1.18, 1.48]) and airflow obstruction (HR [95%CI]: 1.19 [1.07, 1.31]) had a higher risk of developing cirrhosis after adjustments. These associations were consistent across all categories of genetic predisposition, with no observed modifying effect of genetic predisposition. In joint exposure analyses, the highest risk was observed in individuals with both a high genetic predisposition for cirrhosis and PRISm findings (HR [95% CI]: 1.74 [1.45, 2.08]). Our findings indicate that worse pulmonary function is a significant risk factor of cirrhosis, irrespective of genetic predisposition. Early identification and appropriate intervention for pulmonary function may lead to more effective healthcare resource utilization and reduce the burden associated with cirrhosis. • PRISm and genetic risk were associated with development of cirrhosis, respectively. • No significant interaction found between genetic risk and lung function. • In joint, highest risk was observed in those with high genetic risk and PRISm. • PRISm is associated with cirrhosis onset, aiding early detection. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence of small airway abnormalities in smokers despite normal spirometry. The concavity in the descending limb of the maximum expiratory flow curve (MEFV) is a recognised feature of obstruction and can provide information beyond FEV1, and potentially early smoking-related damage. We aimed to evaluate concavity measures compared to known small airway measurements.Methods: Eighty smokers with normal spirometry had small airway function assessed: multiple breath nitrogen washout (MBNW) from which ventilation heterogeneity in the diffusion-dependent acinar (Sacin) and convection-dependent conductive (Scond) airways were assessed, and impulse oscillometry system (IOS) from which respiratory resistance and reactance at 5 Hz (R5 and X5) were measured. Concavity measures were calculated from the MEFV, partitioned into global and peripheral concavity.Results: We found abnormal peripheral and global concavity as well as acinar ventilation heterogeneity are common in "normal" smokers. Concavity measures were not related to either MBNW or IOS measurements.Conclusion: Abnormalities in concavity indices and MBNW or oscillometry parameters are common in smokers despite normal spirometry. However, these measures likely reflect different mechanisms of peripheral airway dysfunction. [ABSTRACT FROM AUTHOR]

BACKGROUND: Severe asthma is a major burden on health-economic resources; hence, knoing the epidemiology of these patients is important in planning and provision of asthma care. In addition, identifying and managing the comorbidities helps improve symptoms and reduce associated morbidity and mortality. OBJECTIVES: Epidemiology of difficult asthma has not been ell studied in the Middle East, so in this study, e present the demographic and clinical characteristics of severe asthma in the United Arab Emirates (UAE). METHODS: We retrospectively revieed the notes of severe asthma patients attending three tertiary care hospitals beteen May 2015 and December 2019. Data on baseline demographics, asthma characteristics, treatment, and comorbidities ere collected. RESULTS: We revieed the notes of 458 patients (271 females and 187 males) that fulfilled the 2019 Global Initiative for Asthma guidelines for the diagnosis of severe asthma. The mean age as 47.7 (standard deviation 17.2) years. Males had significantly higher asthma control test scores (17.9 vs. 16, P = 0.01) and mean blood eosinophils (0.401 vs. 0.294, P

Keywords: Bronchiectasis; Bronchodilators; Long-acting beta dos; Long-acting antimuscarinics; Tiotropium; Exacerbations; Airflow obstruction EN Bronchiectasis Bronchodilators Long-acting beta dos Long-acting antimuscarinics Tiotropium Exacerbations Airflow obstruction 5 7 3 02/28/23 20230201 NES 230201 Bronchiectasis is an irreversible dilatation of the bronchial lumen as a consequence of a pathophysiological vicious circle in which infection, inflammation and remodeling of the bronchial wall play a fundamental role. ERJ Open Res. 2021; 22; 7: 00399-2021 21 Padilla A, Olveira C, Fernandez de Rota L. Factors associated with bronchiectasis in patients with uncontrolled asthma; the NOPES score: a study in 398 patients. In fact, according to the data offered by the most important bronchiectasis registries in the world, between 50 and 70% of patients with bronchiectasis use long-acting 2-adrenoceptors (LABA) and between 15 and 45% use long-acting muscarinic antagonist (LAMA) [[3]]. [Extracted from the article]

RationaleThe Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus (MILES) trial demonstrated that sirolimus stabilized lung function and improved measures of functional performance and quality of life in patients with lymphangioleiomyomatosis. The physiologic mechanisms of these beneficial actions of sirolimus are incompletely understood.ObjectivesTo prospectively determine the longitudinal computed tomographic lung imaging correlates of lung function change in MILES patients treated with placebo or sirolimus.MethodsWe determined the baseline to 12-month change in computed tomographic image-derived lung volumes and the volume of the lung occupied by cysts in the 31 MILES participants (17 in sirolimus group, 14 in placebo group) with baseline and 12-month scans.Measurements and main resultsThere was a trend toward an increase in median expiratory cyst volume percentage in the placebo group and a reduction in the sirolimus group (+2.68% vs. +0.97%, respectively; P = 0.10). The computed tomographic image-derived residual volume and the ratio of residual volume to total lung capacity increased more in the placebo group than in the sirolimus group (+214.4 ml vs. +2.9 ml [P = 0.054] and +0.05 ml vs. -0.01 ml [P = 0.0498], respectively). A Markov transition chain analysis of respiratory cycle cyst volume changes revealed greater dynamic variation in the sirolimus group than in the placebo group at the 12-month time point.ConclusionsCollectively, these data suggest that sirolimus attenuates progressive gas trapping in lymphangioleiomyomatosis, consistent with a beneficial effect of the drug on airflow obstruction. We speculate that a reduction in lymphangioleiomyomatosis cell burden around small airways and cyst walls alleviates progressive airflow limitation and facilitates cyst emptying.

This study aimed to explore the relationship between body mass index (BMI) and abdominal obesity and the risk of airflow obstruction, based on the data from the 2007–2012 National Health and Nutrition Survey (NHANES). Logistic regression was applied to assess the relationships between BMI or abdominal obesity and the risk of airflow obstruction by the fixed ratio method and the lower limit of normal (LLN) method. We further used the restricted cubic splines with 3 knots located at the 5th, 50th, and 95th percentiles of the distribution to evaluate the dose-response relationship. A total of 12,865 individuals aged 20–80 years old were included. In the fixed ratio method, underweight was positively correlated with the risk of airflow obstruction, and overweight and obesity were negatively correlated with the risk of airflow obstruction. In the LLN method, the results were consistent with the fixed ratio method. Abdominal obesity was positively associated with the risk of airflow obstruction only in the fixed ratio method (OR: 1.41, 95% CI: 1.04–1.90). There was an additive interaction between underweight and smoking on airflow obstruction in both methods. Abdominal obesity and smoking had additive interactions in the LLN method. Dose-response analysis indicated that there was a non-linear trend between BMI and the risk of airflow obstruction (Pfor nonlinearity < 0.01). Our study suggested that underweight and abdominal obesity were associated with the increased risk of airflow obstruction, and overweight and general obesity were associated with the decreased risk of airflow obstruction. [ABSTRACT FROM AUTHOR]

Luis Pérez de Llano,1 Marc Miravitlles,2 Rafael Golpe,1 Francisco Javier Alvarez-Gutiérrez,3 Carolina Cisneros,4 Carlos Almonacid,5 Eva Martinez-Moragon,6 Francisco-Javier Gonzalez-Barcala,7 David Ramos-Barbón,8 Vicente Plaza,8 Jose Luis Lopez-Campos,3 Juan Pablo de-Torres,9 Ciro Casanova,10 Juan Luis Garcia Rivero,11 Juan Rodriguez Hermosa,12 Myriam Calle Rubio,12 Juan Jose Soler-Cataluña,13 Borja G Cosio14 1Pneumology Service, University Hospital Lucus Augusti, Lugo, EOXI Cervo, Lugo, Monforte, Spain; 2Pneumology Service, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, CIBERES, Barcelona, Spain; 3Pneumology Service, Hospital Universitario Virgen del Rocio, Seville, Spain; 4Pneumology Service, La Princesa University Hospital, Madrid, Research Institute La Princesa IIP, Madrid, Spain; 5Pneumology Service, Ramón y Cajal Hospital (Ramon y Cajal Health Research Institute, IRYCIS), Madrid, Spain; 6Pneumology Service, Hospital Universitario Dr Peset, Valencia, Spain; 7Faculty of Medicine at the University of Santiago de Compostela, Pneumology Service of the University Clinical Hospital of Santiago de Compostela, CIBERES, Santiago de Compostela, Spain; 8Pneumology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 9Division of Respirology and Sleep Medicine, Queen’s University, Canada, ON, Canada; 10Pneumology Service, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz De Tenerife, Spain; 11Pneumology Service, Hospital de Laredo, Laredo, Spain; 12Pneumology Service and Faculty of Medicine, Hospital Clínico San Carlos, Complutense University of Madrid, Madrid, Spain; 13Pneumology Service, Hospital Arnau de Vilanova, Valencia, Spain; 14Pneumology Service, Son Espases University Hospital, IdISBa, CIBERES, Clínica Quirón-Rotger, Palma, SpainCorrespondence: Borja G CosioPneumology Service, Hospital Universitario Son Espases, IdISBa, CIBERES, Clínica Quirón-Rotger, Ctra. de Valldemossa 79, Palma de Mallorca 07010, SpainTel +34 871 206714 Ext 76714Fax +34 871 909724Email borja.cosio@ssib.esAbstract: Chronic airflow obstruction affects a wide range of airway diseases, the most frequent of which are asthma, COPD, and bronchiectasis; they are clearly identifiable in their extremes, but quite frequently overlap in some of their pathophysiological and clinical characteristics. This has generated the description of new mixed or overlapping disease phenotypes with no clear biological grounds. In this special article, a group of experts provides their perspective and proposes approaching the treatment of chronic airway disease (CAD) through the identification of a series of therapeutic goals (TG) linked to treatable traits (TT) – understood as clinical, physiological, or biological characteristics that are quantifiable using biomarkers. This therapeutic approach needs validating in a clinical trial with the strategy of identification of TG and treatment according to TT for each patient independently of their prior diagnosis.Keywords: airflow obstruction, biomarker, personalised medicine, COPD asthma overlap

Yuji Yamamoto, Keisuke Miki, Takanori Matsuki, Kiyoharu Fukushima, Yohei Oshitani, Hiroyuki Kagawa, Kazuyuki Tsujino, Kenji Yoshimura, Mari Miki, Hiroshi Kida Department of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, Osaka, JapanCorrespondence: Keisuke MikiDepartment of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1 Toneyama, Toyonaka, Osaka 560-8552, JapanTel +81-6-6853-2001Fax +81-6-6853-3127Email miki.keisuke.pu@mail.hosp.go.jpBackground: Oscillometry is a tool to measure respiratory impedance that requires minimal patients’ effort. In patients with chronic obstructive pulmonary disease (COPD), the correlation of respiratory impedance at rest with exertional ventilatory parameters, including exercise tolerance, has scarcely been reported. In addition, the utility of oscillometric parameters might differ between the inspiratory and expiratory phases due to airflow obstruction during expiration, but the hypothesis had not been validated. The aim of the present study was to investigate whether oscillometric parameters are associated with exertional ventilatory parameters in patients with COPD.Methods: Fifty-five subjects with COPD who attended clinics at the National Hospital Organization Osaka Toneyama Medical Center performed spirometry, oscillometry, and cardiopulmonary exercise testing (CPET) within 2 weeks. The correlations between parameters of spirometry, oscillometry, and CPET were analyzed using Spearman’s rank correlation coefficient, univariate, and multivariate analyses.Results: Respiratory reactance had better correlations with the CPET parameters than respiratory resistance. Moreover, inspiratory reactance at rest correlated with the CPET parameters stronger than expiratory reactance. In particular, inspiratory resonant frequency (Fres-ins) correlated with peak oxygen uptake (rS=− 0.549, p< 0.01) and dead space to tidal volume ratio at peak exercise (rS=0.677, p< 0.01) and the best predicted expiratory tidal volume (VT ex) at peak exercise of all the oscillometric parameters (rS=− 0.679, p< 0.01). However, the correlation between Fres-ins and VT ex at peak exercise became weak in subjects with severe and very severe COPD during exercise.Conclusion: Measurement of respiratory reactance is useful for the effortless evaluation of not only exertional ventilatory parameters but exercise tolerance in patients with COPD. The correlation of respiratory impedance with exertional ventilatory parameters can become weak in patients with advanced COPD; thus, the measurement of oscillometry might not be appropriate for evaluating exertional ventilatory parameters of patients with advanced COPD.Keywords: dyspnea, dynamic hyperinflation, airflow obstruction, resonant frequency, tidal volume

Abstract Background A disintegrin and metalloproteinase domain-15 (ADAM15) is expressed by activated leukocytes, and fibroblasts in vitro. Whether ADAM15 expression is increased in the lungs of COPD patients is not known. Methods ADAM15 gene expression and/or protein levels were measured in whole lung and bronchoalveolar lavage (BAL) macrophage samples obtained from COPD patients, smokers, and non-smokers. Soluble ADAM15 protein levels were measured in BAL fluid (BALF) and plasma samples from COPD patients and controls. Cells expressing ADAM15 in the lungs were identified using immunostaining. Staining for ADAM15 in different cells in the lungs was related to forced expiratory volume in 1 s (FEV1), ratio of FEV1 to forced vital capacity (FEV1/FVC), and pack-years of smoking history. Results ADAM15 gene expression and/or protein levels were increased in alveolar macrophages and whole lung samples from COPD patients versus smokers and non-smokers. Soluble ADAM15 protein levels were similar in BALF and plasma samples from COPD patients and controls. ADAM15 immunostaining was increased in macrophages, CD8+ T cells, epithelial cells, and airway α-smooth muscle (α-SMA)-positive cells in the lungs of COPD patients. ADAM15 immunostaining in macrophages, CD8+ T cells and bronchial (but not alveolar) epithelial cells was related inversely to FEV1 and FEV1/FVC, but not to pack-years of smoking history. ADAM15 staining levels in airway α-SMA-positive cells was directly related to FEV1/FVC. Over-expressing ADAM15 in THP-1 cells reduced their release of matrix metalloproteinases and CCL2. Conclusions These results link increased ADAM15 expression especially in lung leukocytes and bronchial epithelial cells to the pathogenesis of COPD.