Association Between Urinary Phthalate Metabolites and Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.

Objective: 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.

Chronic obstructive pulmonary disease related to wood smoke and impact of the combined exposure to tobacco.

BACKGROUND: Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 highlights the need to explore aetiotypes of chronic obstructive pulmonary disease (COPD) beyond the tobacco-smoking COPD. Exposure to wood smoke (WS) is a risk factor for COPD in women, but the effect of the combined exposure to tobacco smoke (TS) in the general population and among COPD patients, and the characteristics of WS-COPD are unclear. METHOD: This was an analysis of data from PREPOCOL (Prevalence of COPD in Five Colombian Cities Situated at Low, Medium, and High Altitude), a random cross-sectional population-based study (n = 5,539) focusing on the effect of combined WS and TS exposure and WS-COPD characterisation. RESULTS: Prevalence of COPD was significantly higher in those exposed to both WS and TS (16.0%) than in those exposed to WS (6.7%) or TS (7.8%) only (P < 0.001). Exposure to WS was associated with COPD in men (OR 1.53, P = 0.017). WS-COPD individuals were more frequently female, older, shorter and had higher forced expiratory volume in 1 sec (FEV1) (all P < 0.05). Those exposed to both WS and TS had more symptoms and worse airflow limitation (P < 0.001). CONCLUSIONS: This was the first random population-based study showing that WS is an associated risk factor for COPD also in men, and that people exposed to both WS and TS have a significantly higher prevalence of COPD. Similarly, COPD subjects exposed to both types of smoke have more symptoms and greater airflow obstruction. This suggests an additive effect of WS and TS.

CONTEXTE: L'Initiative mondiale pour les maladies pulmonaires obstructives chroniques (Global Initiative for Chronic Obstructive Lung Disease, GOLD) 2023 met en évidence l'importance d'explorer les différents étiotypes de la maladie pulmonaire obstructive chronique (COPD, pour l'anglais « chronic obstructive pulmonary disease ¼) en dehors de la COPD liée au tabagisme. L'exposition à la fumée de bois (WS, pour l'anglais « wood smoke ¼) représente un facteur de risque de la COPD chez les femmes, cependant, l'impact de l'exposition simultanée à la fumée de tabac (TS, pour l'anglais « tobacco smoke ¼) chez la population générale et chez les patients atteints de COPD, ainsi que les caractéristiques spécifiques de la WS-COPD, demeurent peu clairs. MÉTHODES: Il s'agit d'une étude transversale aléatoire basée sur la population (n = 5 539) qui analyse les données de PREPOCOL (Prevalence of COPD in Five Colombian Cities Situated at Low, Medium, and High Altitude). L'étude se concentre sur l'effet de l'exposition combinée à la WS et à la TS ainsi que sur la caractérisation de la WS-COPD. RÉSULTATS: La prévalence de la COPD était significativement plus élevée chez les personnes exposées à la fois à la WS et à la TS (16,0%) que chez celles exposées uniquement à la WS (6,7%) ou à la TS (7,8%) (P < 0,001). L'exposition à la WS était associée à la COPD chez les hommes (OR 1,53 ; P = 0,017). Les personnes atteintes de WS-COPD étaient plus fréquemment des femmes, d'un âge plus avancé, de plus petite taille et présentaient un volume expiratoire maximal en 1 seconde (FEV1) plus élevé (tous P < 0,05). Les personnes exposées à la fois à la WS et à la TS ont montré plus de symptômes et une plus grande limitation du débit d'air (P < 0,001). CONCLUSION: Il s'agit de la première étude aléatoire basée sur la population qui démontre que la WS est un facteur de risque lié à la COPD, même chez les hommes, et que les individus exposés à la fois à la WS et à la TS présentent une prévalence significativement plus élevée de la COPD. De plus, les personnes souffrant de COPD qui sont exposés aux deux types de fumée manifestent davantage de symptômes et une obstruction pulmonaire plus sévère. Cela laisse supposer qu'il y a un effet cumulatif de la WS et de la TS.

Dysanapsis Genetic Risk Predicts Lung Function Across the Lifespan.

Rationale Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objective By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. Methods We performed a genome-wide association study (GWAS) of CT-assessed dysanapsis in 11,951 adults, including individuals from two population-based and two COPD-enriched studies. We applied colocalization analysis to integrate GWAS and gene expression data from whole blood and lung. Genetic variants associated with dysanapsis were combined into a genetic risk score that was applied to examine association with lung function in children from a population-based birth cohort (n=1,278) and adults from the UK Biobank (n=369,157). Measurements and Main Results CT-assessed dysanapsis was associated with genetic variants from 21 independent signals in 19 gene regions, implicating HHIP, DSP, and NPNT as potential molecular targets based on colocalization of their expression. Higher dysanapsis genetic risk score was associated with obstructive spirometry among 5 year old children and among adults in the 5th, 6th and 7th decades of life. Conclusions CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endo-phenotype link between the genetic variations associated with lung function and COPD.

Pulmonary function, genetic predisposition, and the risk of cirrhosis: A prospective cohort study.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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]). CONCLUSIONS: 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.

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.

Expiratory flow limitation during mechanical ventilation: real-time detection and physiological subtypes.

BACKGROUND: Tidal expiratory flow limitation (EFLT) complicates the delivery of mechanical ventilation but is only diagnosed by performing specific manoeuvres. Instantaneous analysis of expiratory resistance (Rex) can be an alternative way to detect EFLT without changing ventilatory settings. This study aimed to determine the agreement of EFLT detection by Rex analysis and the PEEP reduction manoeuvre using contingency table and agreement coefficient. The patterns of Rex were explored. METHODS: Medical patients ≥ 15-year-old receiving mechanical ventilation underwent a PEEP reduction manoeuvre from 5 cmH2O to zero for EFLT detection. Waveforms were recorded and analyzed off-line. The instantaneous Rex was calculated and was plotted against the volume axis, overlapped by the flow-volume loop for inspection. Lung mechanics, characteristics of the patients, and clinical outcomes were collected. The result of the Rex method was validated using a separate independent dataset. RESULTS: 339 patients initially enrolled and underwent a PEEP reduction. The prevalence of EFLT was 16.5%. EFLT patients had higher adjusted hospital mortality than non-EFLT cases. The Rex method showed 20% prevalence of EFLT and the result was 90.3% in agreement with PEEP reduction manoeuvre. In the validation dataset, the Rex method had resulted in 91.4% agreement. Three patterns of Rex were identified: no EFLT, early EFLT, associated with airway disease, and late EFLT, associated with non-airway diseases, including obesity. In early EFLT, external PEEP was less likely to eliminate EFLT. CONCLUSIONS: The Rex method shows an excellent agreement with the PEEP reduction manoeuvre and allows real-time detection of EFLT. Two subtypes of EFLT are identified by Rex analysis. TRIAL REGISTRATION: Clinical trial registered with www.thaiclinicaltrials.org (TCTR20190318003). The registration date was on 18 March 2019, and the first subject enrollment was performed on 26 March 2019.

Combining small airway parameters with conventional parameters obtained during spirometry to diagnose airflow obstruction: A cross-sectional study.

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.

Pulmonary function testing in preoperative high-risk patients.

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 < 4) were examined. Clinical characteristics, history of lung diseases, and smoking status were also recorded. The statistical analysis entailed t-tests, one-way ANOVA, and multiple linear regression with backward elimination for group comparisons. RESULTS: Among 256 included patients, 230 fulfilled the test quality criteria. Eighty-one (35.2%) patients presented obstructive ventilatory disorders, out of which 65 were previously unknown. 38 of the newly diagnosed obstructive disorders were mild, 18 moderate, and 9 severe. One hundred forty-five DLCO measurements revealed 40 (27.6%) previously unknown gas exchange impairments; 21 were mild, 17 moderate, and 2 severe. The pulmonary function parameters of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and DLCO were significantly lower than the international reference values of a healthy population. Patients with a lower ASA class and no history of smoking exhibited higher FVC, FEV1, and DLCO values. Reduced exercise tolerance with MET < 4 was strongly associated with lower spirometry values. CONCLUSIONS: Our screening program detected a relevant number of patients with previously unknown obstructive ventilatory disorders and impaired pulmonary gas exchange. This newly discovered sickness is associated with low metabolic equivalents and may influence perioperative outcomes. Whether optimized management of patients with previously unknown impaired lung function leads to a better outcome should be evaluated in multicenter studies. TRIAL REGISTRATION: German Registry of Clinical Studies (DRKS00029337), registered on: June 22nd, 2022.

Comparison of Disease Severity Classifications of Chronic Obstructive Pulmonary Disease: GOLD vs. STAR in Clinical Practice.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), there are two known classifications for assessing what is called disease severity. One is the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, which is based on the post-bronchodilator value of FEV1 (% reference). The other is the STaging of Airflow obstruction by Ratio (STAR), with four grades of severity in subjects with an FEV1/FVC ratio <0.70: STAR 1 ≥0.60 to <0.70, STAR 2 ≥0.50 to <0.60, STAR 3 ≥0.40 to <0.50, and STAR 4 <0.40. PURPOSE: The aim of this study was to compare the staging of COPD using the GOLD and STAR classifications in clinical practice. METHODS: We reanalyzed data from our outpatient cohort study, which included 141 participants with COPD from 2015 to 2023. We compared mortality and COPD-specific health status between the GOLD 1 to 4 groups and the STAR 1 to 4 groups. RESULTS: By simple calculation, GOLD and STAR severity classes coincided in 75 participants (53.2%). The weighted Bangdiwala B value with linear weights was 0.775. The participants were observed for up to 95 months, with a median of 54 months. Death was confirmed in 29 participants (20.5%). In univariate Cox proportional hazards analyses, there was a significant difference in mortality between the GOLD 1 and GOLD 3 + 4 groups, with the GOLD 1 group used as the reference [hazard ratio 4.222 (95% CI 1.298-13.733), p = 0.017]. However, there was no statistically significant predictive relationship between STAR 1 and STAR 2, or between STAR 1 and STAR 3 + 4. St. George's Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) scores were significantly different between all GOLD groups, except for the CAT score between GOLD 1 and GOLD 2. The SGRQ Total and CAT scores were significantly different between STAR 1 and STAR 3 + 4, but not between STAR 1 and STAR 2. CONCLUSION: From the perspective of all-cause mortality and COPD-specific health status, the GOLD classification is more discriminative than STAR.

Airway tree caliber heterogeneity and airflow obstruction among older adults.

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.

Increased blood eosinophils and airflow obstruction as new-onset asthma predictors in the elderly: The Nagahama study.

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.

Association of spirometric restriction with mortality in the silicotics: a cohort study.

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.

Reduced lung function and cause-specific mortality: A population-based study of Norwegian men followed for 26 years.

BACKGROUND AND AIM: Reduced lung function is associated with increased mortality, but it is unclear how different spirometric patterns are related to specific deaths. Aim of this study was to investigate these associations in a large general population cohort. METHODS: The study population consisted of 26,091 men aged 30-46 years from the Pneumoconiosis Survey of Western Norway conducted in 1988-1990 with follow-up on date and cause of death for 26 years. Cox proportional hazard models were used to estimate the association between baseline FEV1, FVC, obstructive (OSP) and restrictive spirometric pattern (RSP) (z-scores calculated according to GLI-2012 equations) and mortality (European 2012 shortlist classification (E-2012)), after adjustment for age, body mass index, smoking habits, and education. RESULTS: In total, 2462 (9%) subjects died. A predominant reduction of FEV1 (and OSP) were associated with respiratory non-cancer (E-8) (HR for one unit FEV1 z-score decrease 2.29 (95% CI 1.90, 2.77) and lung cancer mortality (E-2.1.8) (1.27(1.12, 1.44)). A similar reduction of FEV1 and FVC (and RSP) were associated with diabetes (E-4.1) (FEV1 2.21(1.67, 2.92), FVC 2.41(1.75, 3.32)), cerebrovascular (E-7.3) (1.52(1.21, 1.91), 1.54(1.19, 1.98)), ischemic heart disease (E-7.1) (1.22(1.10, 1.35), 1.21(1.08, 1.36)), neurological (E-6.3) (1.56(1.21, 2.01), 1.61(1.22, 2.13)), suicide (E-17.2) (1.37(1.13, 1.65), 1.29(1.04, 1.59)) and hematological cancer mortality (E-2.1.19-21) (1.29(1.05, 1.58), (1.26(1.00, 1.58)). No association was found between reduced lung function and mortality due to accidents, alcohol abuse, digestive and genitourinary cancer. CONCLUSIONS: Spirometric obstruction was mainly related to pulmonary mortality. Spirometric restriction was mainly related to extra-pulmonary mortality.

Effects of elexacaftor-tezacaftor-ivacaftor on daily treatment burden and airflow obstruction in adults with cystic fibrosis.

BACKGROUND: The drug combination elexacaftor-tezacaftor-ivacaftor (ETI) proved highly effective in the improvement of the respiratory symptoms, the percentage of predicted forced expiratory volume in 1 s (FEV1), and to reduce rates of pulmonary exacerbations in people with cystic fibrosis (CF) with at least one F508del mutation. The objectives of the study were to evaluate the impact of ETI on the daily treatment burden due to patient decision and the evolution of lung function parameters at 6 months of treatment in real life. METHODS: A single-center observational study was realized including adult patients starting ETI therapy from March 10, 2020 to April 5, 2022. Clinical characteristics were collected at initiation (T0) and at 6 months (T6) of treatment. Outcome measures included names and number of chronic daily medications, respectively lung function parameters: FEV1, forced vital capacity (FVC), FEV1/FVC ratio, peak expiratory flow (PEF), forced expiratory flow at 25-75% of FVC (FEF25-75), ß-angle and FEF50/PEF ratio. RESULTS: Sixty-five patients were included with a mean age of 29.4 ± 8.5 years old, 48% of them F508del homozygous previously treated by lumacaftor-ivacaftor. At T6, the median number of daily medications decreased from 13 [2-24] to 9 [1-19] (p < 0.001). All the studied functional respiratory parameters were improved: FEV1 +18%, FVC +14%, FEF25-75% + 18% (all p < 0.001), as well the airflow obstruction: FEV1/FVC +6%, FEF50/PEF by 0.1 ± 0.1 and ß-angle by 10° ± 13° (all p ≤ 0.007). CONCLUSION: ETI therapy can reduce the daily treatment burden in real-life at 6 months of treatment, increase a large number of lung function parameters and improve airflow obstruction.

Impaired Skeletal Muscle in Patients with Stable Chronic Obstructive Pulmonary Disease (COPD) Compared with Non-COPD Patients.

Purpose: 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 (ß = -0.107, P < 0.001), gender (ß = 0.212, P < 0.001), body mass index (BMI) (ß = 0.462, P < 0.001), FEV1% (ß = 0.108, P = 0.009), and calf circumference (CC) (ß = 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.

FEV1/FVC Severity Stages for Chronic Obstructive Pulmonary Disease.

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-and applied to the combined Pittsburgh 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.

Patients With Asthma Only Sensitized to Staphylococcus aureus Enterotoxins Have More Exacerbations, Airflow Limitation, and Higher Levels of Sputum IL-5 and IgE.

BACKGROUND: Staphylococcus aureus enterotoxins (SE) may act as superantigens and induce an intense T-cell activation, causing local production of polyclonal IgE and resultant eosinophil activation. OBJECTIVE: To assess whether asthma with sensitization to SE but not to common aeroallergens (AAs) displays different inflammatory characteristics. METHODS: We conducted a prospective study on a series of 110 consecutive patients with asthma recruited from the University Asthma Clinic of Liège. We compared clinical, functional, and inflammatory characteristics of this general population of patients with asthma categorized into 4 groups according to sensitization to AAs and/or SE. We also compared sputum supernatant cytokines in patients sensitized to SE or not. RESULTS: Patients with asthma sensitized only to AAs represented 30%, while 29% were sensitized to both AAs and SE. One-fifth of the population had no specific IgE. Sensitization to SE but not to AA (21%) was associated with later onset of disease, higher rate of exacerbations, nasal polyps, and more severe airway obstruction. As for airway type 2 biomarkers, patients presenting with specific IgE against SE displayed higher fractional exhaled nitric oxide, sputum IgE, and sputum IL-5 levels but not IL-4. We confirm that the presence of specific IgE against SE is associated with elevated serum IgE to levels well above those observed in patients sensitized only to AAs. CONCLUSIONS: Our study suggests that asthma specialists should measure specific IgE against SE during the phenotyping process because it may allow the identification of a subgroup of patients with more asthma exacerbations, more nasal polyposis and chronic sinusitis, lower lung function, and more intense type 2 inflammation.

Comparative assessment of small airway dysfunction by impulse oscillometry and spirometry in chronic obstructive pulmonary disease and asthma with and without fixed airflow obstruction.

Background: Small airways play a major role in the pathogenesis and prognosis of chronic obstructive pulmonary disease (COPD) and asthma. More data on small airway dysfunction (SAD) using spirometry and impulse oscillometry (IOS) in these populations are required. The objective of this study was to compare the two methods, spirometry and IOS, for SAD detection and its prevalence defined by spirometry and IOS in subjects with COPD and asthma with and without fixed airflow obstruction (FAO). Design: This is a cross-sectional study. Methods: Spirometric and IOS parameters were compared across four groups (COPD, asthma with FAO, asthma without FAO, and healthy subjects). SAD defined by spirometry and IOS criteria were compared. Results: A total of 262 subjects (67 COPD, 55 asthma with FAO, 101 asthma without FAO, and 39 healthy controls) were included. The prevalence of SAD defined by using IOS and spirometry criteria was significantly higher in patients with COPD (62.7 and 95.5%), asthma with FAO (63.6 and 98.2%), and asthma without FAO (38.6 and 19.8%) in comparison with healthy control (7.7 and 2.6%). IOS is more sensitive than spirometry in the detection of SAD in asthma without FAO (38.6% vs. 19.8%, p = 0.003) However, in subjects with FAO (COPD and asthma with FAO), spirometry is more sensitive than IOS to detect SAD (95.5% vs. 62.7%, p < 0.001 and 98.2% vs. 63.6%, p < 0.001, respectively). Conclusion: Small airway dysfunction was significantly detected in COPD and asthma with and without FAO. Although IOS shows more sensitivity than spirometry in the detection of SAD in asthma without FAO, spirometry is more sensitive than IOS in patients with FAO including COPD and asthma with FAO.