Forced Expiratory Volume In 1 S/forced Vital Capacity Research Articles

Development and validation of a mortality risk prediction model for chronic obstructive pulmonary disease: a cross-sectional study using probabilistic graphical modelling

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of mortality. Predicting mortality risk in patients with COPD can be important for disease management strategies. Although all-cause mortality predictors have been developed previously, limited research exists on factors directly affecting COPD-specific mortality. In a retrospective study, we used probabilistic graphs to analyse clinical cross-sectional data (COPDGene cohort), including demographics, spirometry, quantitative chest imaging, and symptom features, as well as gene expression data. COPDGene recruited current and former smokers, aged 45-80 years with >10 pack-years smoking history, from across the USA (Phase 1, 11/2007-4/2011) and invited them for a follow-up visit (Phase 2, 7/2013-7/2017). ECLIPSE cohort recruited current and former smokers (COPD patients and controls from USA and Europe), aged 45-80 with smoking history >10 pack-years (12/2005-11/2007). We applied graphical models on multi-modal data COPDGene Phase 1 participants to identify factors directly affecting all-cause and COPD-specific mortality (primary outcomes); and on Phase 2 follow-up cohort to identify additional molecular and social factors affecting mortality. We used penalized Cox regression with features selected by the causal graph to build VAPORED, a mortality risk prediction model. VAPORED was compared to existing scores (BODE: BMI, airflow obstruction, dyspnoea, exercise capacity; ADO: age, dyspnoea, airflow obstruction) on the ability to rank individuals by mortality risk, using four evaluation metrics (concordance, concordance probability estimate (CPE), cumulative/dynamic (C/D) area under the receiver operating characteristic curve (AUC), and integrated C/D AUC). The results were validated in ECLIPSE. Graphical models, applied on the COPDGene Phase 1 samples (n=8610), identified 11 and 7 variables directly linked to all-cause and COPD-specific mortality, respectively. Although many appear in both models, non-lung comorbidities appear only in the all-cause model, while forced vital capacity (FVC %predicted) appears in COPD-specific mortality model only. Additionally, the graph model of Phase 2 data (n=3182) identified internet access, CD4 T cells and platelets to be linked to lower mortality risk. Furthermore, using the 7 variables linked to COPD-specific mortality (forced expiratory volume in 1s/forced vital capacity (FEV1/FVC) ration, FVC %predicted, age, history of pneumonia, oxygen saturation, 6-min walk distance, dyspnoea) we developed VAPORED mortality risk score, which we validated on the ECLIPSE cohort (3-yr all-cause mortality data, n=2312). VAPORED performed significantly better than ADO, BODE, and updated BODE indices in predicting all-cause mortality in ECLIPSE in terms of concordance (VAPORED [0.719] vs ADO [0.693; FDR p-value 0.014], BODE [0.695; FDR p-value 0.020], and updated BODE [0.694; FDR p-value 0.021]); CPE (VAPORED [0.714] vs ADO [0.673; FDR p-value <0.0001], BODE [0.662; FDR p-value <0.0001], and updated BODE [0.646; FDR p-value <0.0001]); 3-year C/D AUC (VAPORED [0.728] vs ADO [0.702; FDR p-value 0.017], BODE [0.704; FDR p-value 0.021], and updated BODE [0.703; FDR p-value 0.024]); integrated C/D AUC (VAPORED [0.723] vs ADO [0.698; FDR p-value 0.047], BODE [0.695; FDR p-value 0.024], and updated BODE [0.690; FDR p-value 0.021]). Finally, we developed a web tool to help clinicians calculate VAPORED mortality risk and compare it to ADO and BODE predictions. Our work is an important step towards improving our identification of high-risk patients and generating hypotheses of potential biological mechanisms and social factors driving mortality in patients with COPD at the population level. The main limitation of our study is the fact that the analysed datasets consist of older people with extensive smoking history and limited racial diversity. Thus, the results are relevant to high-risk individuals or those diagnosed with COPD and the VAPORED score is validated for them. This research was supported by NIH [NHLBI, NLM]. The COPDGene study is supported by the COPD Foundation, through grants from AstraZeneca, Bayer Pharmaceuticals, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer and Sunovion.

A metagenomic next-generation sequencing (mNGS)-based analysis of bronchoalveolar lavage samples in patients with an acute exacerbation of chronic obstructive pulmonary disease.

The role of the bronchoalveolar lavage fluid (BALF) microbiome in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains unclear. The advent of the metagenomic next-generation sequencing (mNGS) has made it possible to reveal the complex microbiome composition of the respiratory tract. This study aimed to explore whether there are differences in the BALF microbiome of AECOPD patients with different lung functions. We enrolled 55 AECOPD patients and divided them into a mild group (n = 31) and a severe group (n = 24) according to their lung function. We collected BALF and submitted it to mNGS and bioinformatics analysis. At the species level, mNGS identified 264 bacteria, 13 fungi and 12 viruses in the mild group, and 174 bacteria, 6 fungi and 6 viruses in the severe group. Mixed bacterial and viral infection occurred in both groups. At the genus level, Rothia and Veillonella were more abundant in the mild group, while Pseudomonas and Staphylococcus were more abundant in the severe group. At the species level, compared with the mild group, the relative abundance of Haemophilus influenzae and Pseudomonas aeruginosa was increased in the severe group. Besides, the BALF microbiome composition was similar between the two groups, and there was no significant difference in α and β diversity. Forced expiratory volume in 1s/forced vital capacity (FEV1/FVC) (%) showed no significant correlation with the Shannon or Simpson index. The microbiome abundance was different between the mild and severe groups; however, microbiome diversity was similar between the two groups. Based on our findings, Haemophilus influenzae and Pseudomonas aeruginosa may be the pathogenic bacteria that cause the difference in lung function in patients with AECOPD.

Construction and validation of a risk prediction model for postoperative ICU admission in patients with colorectal cancer: clinical prediction model study

BackgroundTransfer to the ICU is common following non-cardiac surgeries, including radical colorectal cancer (CRC) resection. Understanding the judicious utilization of costly ICU medical resources and supportive postoperative care is crucial. This study aimed to construct and validate a nomogram for predicting the need for mandatory ICU admission immediately following radical CRC resection.MethodsRetrospective analysis was conducted on data from 1003 patients who underwent radical or palliative surgery for CRC at Ningxia Medical University General Hospital from August 2020 to April 2022. Patients were randomly assigned to training and validation cohorts in a 7:3 ratio. Independent predictors were identified using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression in the training cohort to construct the nomogram. An online prediction tool was developed for clinical use. The nomogram's calibration and discriminative performance were assessed in both cohorts, and its clinical utility was evaluated through decision curve analysis (DCA).ResultsThe final predictive model comprised age (P = 0.003, odds ratio [OR] 3.623, 95% confidence interval [CI] 1.535–8.551); nutritional risk screening 2002 (NRS2002) (P = 0.000, OR 6.129, 95% CI 2.920–12.863); serum albumin (ALB) (P = 0.013, OR 0.921, 95% CI 0.863–0.982); atrial fibrillation (P = 0.000, OR 20.017, 95% CI 4.191–95.609); chronic obstructive pulmonary disease (COPD) (P = 0.009, OR 8.151, 95% CI 1.674–39.676); forced expiratory volume in 1 s / Forced vital capacity (FEV1/FVC) (P = 0.040, OR 0.966, 95% CI 0.935–0.998); and surgical method (P = 0.024, OR 0.425, 95% CI 0.202–0.891). The area under the curve was 0.865, and the consistency index was 0.367. The Hosmer–Lemeshow test indicated excellent model fit (P = 0.367). The calibration curve closely approximated the ideal diagonal line. DCA showed a significant net benefit of the predictive model for postoperative ICU admission.ConclusionPredictors of ICU admission following radical CRC resection include age, preoperative serum albumin level, nutritional risk screening, atrial fibrillation, COPD, FEV1/FVC, and surgical route. The predictive nomogram and online tool support clinical decision-making for postoperative ICU admission in patients undergoing radical CRC surgery.Trial registrationDespite the retrospective nature of this study, we have proactively registered it with the Chinese Clinical Trial Registry. The registration number is ChiCTR2200062210, and the date of registration is 29/07/2022.

Association Between Osteoporosis Self-Assessment Tool for Asians and Airflow Limitation in Japanese Post-Menopausal Women.

This study aimed to reveal the association between the osteoporosis self-assessment tool for Asians (OSTA) and airflow limitation (AL) in post-menopausal Japanese women. This cross-sectional study included 1580 participants undergoing a comprehensive health examination using spirometry and dual-energy X-ray absorptiometry. The OSTA was calculated by subtracting the age in years from the body weight (BW) in kilograms, and the result was multiplied by 0.2. The OSTA risk level was defined as low (>-1), moderate (-4 to -1), or high (<-4). AL was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7. The association between the OSTA and AL was assessed using logistic regression analysis. The prevalence of AL was significantly higher in the high OSTA group (15.3%) than in the low OSTA group (3.1%) (p<0.001). In multiple linear regression analysis, the OSTA was independently associated with FEV1/FVC. In logistic regression models adjusted for smoking status, alcohol consumption, current use of medication for diabetes, hyperglycemia, rheumatoid arthritis, second-hand smoke, and ovary removal showed a significantly higher risk of AL (odds ratio: 5.48; 95% confidence interval: 2.90-10.37; p<0.001) in participants with OSTA high risk than in those with OSTA low risk. These results suggest that the OSTA high risk indicates reduced BMD at the femoral neck and presence of AL in Japanese post-menopausal women aged ≥45 years.

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

BackgroundIt has been known that smoking and various lung diseases including lung cancer can cause lung function impairment. However, the impact of different types of lung function impairments, such as...

GLI-12 Reference Values versus Fixed 0.7 Ratio for the Detection of Airflow Obstruction in the Presence of Lung Hyperinflation

Introduction: Airflow obstruction (AO) is evidenced by reduced forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) with the threshold for diagnosis often being set at <0.7. However, currently the ATS/ERS standards for interpretation of lung function tests recommend the lower limit of normal (LLN), calculated by reference equations of the Global Lung Initiative from 2012 (GLI-12), as a threshold for AO diagnosis. The present study aims to investigate phenotypes, with focus on hyperinflation, which influence AO prevalence defined by FEV1/FVC < LLN when compared to the fixed 0.7 threshold. Methods: Data from 3,875 lung function tests (56.4% men, aged 18–95) including 3,824 body plethysmography recordings performed from July 2021 to June 2022 were analysed. The difference between both classifiers was quantified, before and after stratification by sex, age, and hyperinflation. Results: AO diagnosis was significantly less frequent with the LLN threshold (18.2%) compared to the fixed threshold (28.0%) (p < 0.001) with discordance rate of 10.5%. In the presence of mild or moderate hyperinflation, there was substantial agreement (Cohen’s kappa: 0.616, 0.718) between the classifiers compared to near perfect agreement in the presence of severe hyperinflation (Cohen’s kappa: 0.896). In addition, subgroup analysis after stratification for sex, age, and hyperinflation showed significant differences between both classifiers. Conclusion: The importance of using the LLN threshold instead of the fixed 0.7 threshold for the diagnosis of AO is highlighted. When using the fixed threshold AO, misdiagnosis was more common in the presence of mild to moderate hyperinflation.

Changes and clinical significance of serum MMP-9, TIMP-1, COX-2, and immune levels in patients with asthma

Objective: To detect serum metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases (TIMP-1), cyclooxygenase-2 (COX-2), and T helper cells 1–T helper cells 2 (Th1–Th2) levels in asthma patients and assess their clinical significance. Methods: A total of 72 patients experiencing acute asthma (acute group), 66 stable asthma patients (stable group), and 60 healthy volunteers (control group) were included in this study. The levels of TIMP-1, COX-2, and Th1–Th2 in patients with acute asthma were measured following treatment with budesonide aerosol inhalation. In addition, the levels of MMP-9, TIMP-1, COX-2 and Th1–Th2 were compared in patients with different severity of acute asthma before and after treatment. Results: The serum levels of MMP-9, TIMP-1, and COX-2 showed an increasing trend in the control, stable, and acute groups, while levels of Th1–Th2 showed a sequential decreasing trend, and the differences were statistically significant. Comparison of lung function indexes among the three groups of patients established a negative correlation between serum MMP-9 and its forced vital capacity% predicted (FEV%pred), TIMP-1, and COX-2, and FEV%pred and forced expiratory volume in 1 s–forced vital capacity (FEV1/FVC) levels, but a positive correlation between Th1–Th2 and FEV1/FVC levels in the acute group. A significant difference was observed on comparing the levels of serum MMP-9, TIMP-1, COX-2, and Th1–Th2 in patients with different conditions in the acute group. Specifically, as the condition worsened, a significant increase in serum MMP-9, TIMP-1, and COX-2 levels but a significant decrease in Th1–Th2 levels was observed. After treatment, we observed a significant decrease in serum MMP-9, TIMP-1, and COX-2 levels but a significant increase in Th1–Th2 levels in the acute group. Conclusion: The serum levels of MMP-9, TIMP-1, COX-2, and Th1–Th2 are valuable indicators reflecting the condition of asthma patients and could be considered promising clinical monitoring indicators.

Quantitative CT at Follow-Up of COVID-19 Pneumonia: Relationship with Pulmonary Function Tests.

The role of quantitative chest computed tomography (CT) is controversial in the follow-up of patients with COVID-19 pneumonia. The aim of this study was to test during the follow-up of COVID-19 pneumonia the association between pulmonary function tests (PFTs) and quantitative parameters extrapolated from follow-up (FU) CT scans performed at least 6 months after COVID-19 onset. The study included patients older than 18 years old, admitted to the emergency department of our institution between 29 February 2020 and 31 December 2020, with a diagnosis of COVID-19 pneumonia, who underwent chest CT at admission and FU CT at least 6 months later; PFTs were performed within 6 months of FU CT. At FU CT, quantitative parameters of well-aerated lung and pneumonia extent were identified both visually and by software using CT density thresholds. The association between PFTs and quantitative parameters was tested by the calculation of the Spearman's coefficient of rank correlation (rho). The study included 40 patients (38% females; median age 63 years old, IQR, 56-71 years old). A significant correlation was identified between low attenuation areas% (%LAAs) <950 Hounsfield units (HU) and both forced expiratory volume in 1s/forced vital capacity (FEV1/FVC) ratio (rho -0.410, 95% CIs -0.639--0.112, p = 0.008) and %DLCO (rho -0.426, 95% CIs -0.678--0.084, p = 0.017). The remaining quantitative parameters failed to demonstrate a significant association with PFTs (p > 0.05). At follow-up, CT scans performed at least 6 months after COVID-19 pneumonia onset showed %LAAs that were inversely associated with %DLCO and could be considered a marker of irreversible lung damage.

IL-25 induces airway remodeling in asthma by orchestrating the phenotypic changes of epithelial cell and fibrocyte

BackgroundPrevious studies have shown that IL-25 levels are increased in patients with asthma with fixed airflow limitation (FAL). However, the mechanism by which IL-25 contributes to airway remodeling and FAL remains unclear. Here, we hypothesized that IL-25 facilitates pro-fibrotic phenotypic changes in bronchial epithelial cells (BECs) and circulating fibrocytes (CFs), orchestrates pathological crosstalk from BECs to CFs, and thereby contributes to airway remodeling and FAL.MethodsFibrocytes from asthmatic patients with FAL and chronic asthma murine models were detected using flow cytometry, multiplex staining and multispectral imaging analysis. The effect of IL-25 on BECs and CFs and on the crosstalk between BECs and CFs was determined using cell culture and co-culture systems.ResultsWe found that asthmatic patients with FAL had higher numbers of IL-25 receptor (i.e., IL-17RB)+-CFs, which were negatively correlated with forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC). The number of airway IL-17RB+-fibrocytes was significantly increased in ovalbumin (OVA)- and IL-25-induced asthmatic mice versus the control subjects. BECs stimulated with IL-25 exhibited an epithelial-mesenchymal transition (EMT)-like phenotypic changes. CFs stimulated with IL-25 produced high levels of extracellular matrix (ECM) proteins and connective tissue growth factors (CTGF). These profibrotic effects of IL-25 were partially blocked by the PI3K-AKT inhibitor LY294002. In the cell co-culture system, OVA-challenged BECs facilitated the migration and expression of ECM proteins and CTGF in CFs, which were markedly blocked using an anti-IL-17RB antibody.ConclusionThese results suggest that IL-25 may serve as a potential therapeutic target for asthmatic patients with FAL.

Lung function, respiratory symptoms and incident venous thromboembolism during a 44-year follow-up

BackgroundChronic obstructive pulmonary disease (COPD) and infections are risk factors for venous thromboembolism (VTE), but the reasons behind the associations are not fully known. Few studies have investigated whether lung function and respiratory symptoms in individuals without COPD are associated with VTE. ObjectivesTo study the incidence of VTE in individuals without COPD and other major VTE risk factors, in relation to baseline lung function and respiratory symptoms, through a 44-year follow-up prospective cohort study. MethodsAs part of a health screening program, a total of 20,253 men and 7361 women underwent a baseline examination from 1974 to 1992, including a spirometry test and a self-administered questionnaire about respiratory symptoms, e.g., chronic bronchitis, cough, phlegm, and dyspnoea. Lung function was assessed through quartiles of forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC). Through linkage with national registers, all individuals were followed for incidence of VTE. ResultsRespiratory symptoms (cough and dyspnoea) at baseline were associated with an increased risk of incident VTE in women after adjustments for age, height, BMI, smoking status, varicose veins, and FEV1/FVC. The adjusted hazard ratio in relation to chronic bronchitis was 1.57 (95% confidence interval 1.17–2.11). Poor lung function was not associated with an increased risk of VTE after adjustments for potential confounders. ConclusionWomen with respiratory symptoms of cough and dyspnoea without COPD have an increased risk of VTE, independent of lung function and major VTE risk factors. Further studies are needed to confirm the association and to study the clinical applicability of the results.

Association between Respiratory Function and Motor Function in Different Stages of Parkinson’s Disease

Introduction: Respiratory dysfunction in patients with Parkinson’s disease (PD) could present in the early stage and worsen in the late stages. These changes could be a factor affecting the ability of daily living and quality of life of patients with PD. The primary objective of this study was to assess the respiratory function and its association with motor function in patients with different stages of PD. Methods: This was a cross-sectional study conducted at the Huashan Hospital of Fudan University in Shanghai, China. The study included 65 patients diagnosed with PD (the Hoehn and Yahr scale between 1 and 4) and 20 healthy individuals of similar age, gender, weight, and height. The ventilatory function was assessed using the spirometry. Motor function was evaluated using subscale III of the United Parkinson’s disease rating scale (UPDRS-III). After confirming the normality of data distribution, we performed one-way ANOVA with a Tukey’s post hoc test. Results: Compared with the healthy individuals, there was no statistical significance in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) in the H&Y 1 group and H&Y 2 group (p > 0.05) but reduced peak expiratory flow (PEF) in the H&Y 2 group (p = 0.002). Reduced FVC, FEV1, and PEF was seen in the H&Y 3 group (p = 0.002, p = 0.001, and p = 0.0001, respectively). Reduced FVC, FEV1, PEF, and FEF_25–75% was seen in the H&Y 4 group (p = 0.001, p = 0.0001, p = 0.0001, and p = 0.025, respectively). The correlation analysis revealed that there was a significant negative correlation between FVC and UPDRS-III scores (r = −0.248, p = 0.046), disease duration (r = −0.276, p = 0.026), H&Y scale (r = −0.415, p = 0.001). FEV1 was negatively correlated with UPDRS-III scores (r = −0.277, p = 0.025), disease duration (r = −0.291, p = 0.019), H&Y scale (r = −0.434, p = 0.0001). FEF_25–75% was negatively correlated with disease duration (r = −0.247, p = 0.047), H&Y scale (r = −0.278, p = 0.025). Conclusion: Our findings revealed that respiratory impairment is present in moderate and advanced PD patients, and directly related to the severity of the disease. It is important to conduct respiratory function test in the clinical practice.

Changes and clinical significance of serum MMP-9, TIMP-1, COX-2, and immune levels in patients with asthma.

To detect serum metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases (TIMP-1), cyclooxygenase-2 (COX-2), and T helper cells 1-T helper cells 2 (Th1-Th2) levels in asthma patients and assess their clinical significance. A total of 72 patients experiencing acute asthma (acute group), 66 stable asthma patients (stable group), and 60 healthy volunteers (control group) were included in this study. The levels of TIMP-1, COX-2, and Th1-Th2 in patients with acute asthma were measured following treatment with budesonide aerosol inhalation. In addition, the levels of MMP-9, TIMP-1, COX-2 and Th1-Th2 were compared in patients with different severity of acute asthma before and after treatment. The serum levels of MMP-9, TIMP-1, and COX-2 showed an increasing trend in the control, stable, and acute groups, while levels of Th1-Th2 showed a sequential decreasing trend, and the differences were statistically significant. Comparison of lung function indexes among the three groups of patients established a negative correlation between serum MMP-9 and its forced vital capacity% predicted (FEV%pred), TIMP-1, and COX-2, and FEV%pred and forced expiratory volume in 1 s-forced vital capacity (FEV1/FVC) levels, but a positive correlation between Th1-Th2 and FEV1/FVC levels in the acute group. A significant difference was observed on comparing the levels of serum MMP-9, TIMP-1, COX-2, and Th1-Th2 in patients with different conditions in the acute group. Specifically, as the condition worsened, a significant increase in serum MMP-9, TIMP-1, and COX-2 levels but a significant decrease in Th1-Th2 levels was observed. After treatment, we observed a significant decrease in serum MMP-9, TIMP-1, and COX-2 levels but a significant increase in Th1-Th2 levels in the acute group. The serum levels of MMP-9, TIMP-1, COX-2, and Th1-Th2 are valuable indicators reflecting the condition of asthma patients and could be considered promising clinical monitoring indicators.

Trends of COPD in Spain: Changes Between Cross Sectional Surveys 1997, 2007 and 2017

IntroductionWe aim to describe the changes in prevalence and risk factors associated to chronic obstructive pulmonary disease (COPD) in Spain, comparing three population-based studies conducted in three timepoints. MethodsWe compared participants from IBERPOC conducted in 1997, EPISCAN conducted in 2007 and EPISCAN II in 2017. COPD was defined as a postbronchodilator FEV1/FVC (forced expiratory volume in 1s/forced vital capacity) ratio <0.70, according to GOLD criteria; subsequently, also as the FEV1/FVC below the lower limit of normal (LLN). ResultsCOPD prevalence in the population between 40 and 69 years decreased from 21.6% (95% CI 20.7%–23.2%) in 1997 to 8.8% (95% CI 8.2%–9.5%) in 2017, a 59.2% decline (p<0.001).In 2007, the prevalence was 7.7% (95% CI 6.8%–8.7%) with an upward trend of 1.1 percentage points in 2017 (p=0.073). Overall COPD prevalence decreased in men and women, although a significant increase was observed in the last decade in females (p<0.05). Current smokers significantly increased in the last decades (25.4% in 1997, 29.1% in 2007 and 23.4% in 2017; p<0.001). Regrettably, COPD underdiagnosis was constantly high, 77.6% in 1997, 78.4% in 2007, and to 78.2% in 2017 (p=0.95), higher in younger ages (40–49 yrs and 50–59 yrs) and also higher in women than in men in all three studies (p<0.05). ConclusionsWe report a significant reduction of 59.2% in the prevalence of COPD in Spain from 1997 to 2017 in subjects aged 40–69 years. Our study highlights the significant underdiagnosis of COPD, particularly sustained in women and younger populations.

Unravelling young COPD and pre-COPD in the general population.

Chronic obstructive pulmonary disease (COPD) is commonly diagnosed when the airflow limitation is well established and symptomatic. We aimed to identify individuals at risk of developing COPD according to the concept of pre-COPD and compare their clinical characteristics with 1) those who have developed the disease at a young age, and 2) the overall population with and without COPD. The EPISCAN II study is a cross-sectional, population-based study that aims to investigate the prevalence of COPD in Spain in subjects ≥40 years of age. Pre-COPD was defined as the presence of emphysema >5% and/or bronchial thickening by computed chromatography (CT) scan and/or diffusing capacity of the lung for carbon monoxide (D LCO) <80% of predicted in subjects with respiratory symptoms and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) >0.70. Young COPD was defined as FEV1/FVC <0.70 in a subject ≤50 years of age. Demographic and clinical characteristics were compared among pre-COPD, young COPD and the overall population with and without COPD. Among the 1077 individuals with FEV1/FVC <0.70, 65 (6.0%) were ≤50 years of age. Among the 8015 individuals with FEV1/FVC >0.70, 350 underwent both D LCO testing and chest CT scanning. Of those, 78 (22.3%) subjects fulfilled the definition of pre-COPD. Subjects with pre-COPD were older, predominantly women, less frequently active or ex-smokers, with less frequent previous diagnosis of asthma but with higher symptomatic burden than those with young COPD. 22.3% of the studied population was at risk of developing COPD, with similar symptomatic and structural changes to those with well-established disease without airflow obstruction. This COPD at-risk population is different from those that develop COPD at a young age.

Aberrant mitochondrial DNA methylation and declined pulmonary function in a population with polycyclic aromatic hydrocarbon composition in particulate matter

Air pollution exposure has been found to be associated with epigenetic modification of the mitochondrial genome, which could subsequently induce adverse health outcomes. However, very limited studies exist regarding the association between fine particulate matter (PM2.5) exposure and pulmonary function at the molecular level of mitochondrial epigenetic changes. This study aimed to investigate the association of platelet mitochondrial DNA (mtDNA) methylation with occupational PM2.5 exposure and pulmonary function. First, 768 participants were occupationally exposed to polycyclic aromatic hydrocarbon (PAH)-enriched PM2.5 in a coke-oven plant in East China. The levels of PM2.5, PAH components bound to PM2.5, and urinary PAH metabolites in the workplace environment were measured as an internal dose, respectively. mtDNA methylation was measured by bisulfite pyrosequencing of two genes of ATP synthase (MT-ATP6 and MT-ATP8). Mediation analysis was conducted to evaluate the role of mtDNA methylation in pulmonary alteration induced by PAH. A decreasing trend of platelet mtDNA methylation was observed with increase in PM2.5 exposure across all participants. As an important PAH metabolite in urine, 1-hydroxypyrene (1-OHP) was significantly negatively associated with FEV1/FVC (Forced Expiratory Volume in 1s/Forced Vital Capacity) ratio. The participants with high serum folate levels (≥10 nmol/L) showed positive association between MT-ATP6 methylation and FEV1/FVC ratio. Mediation analysis suggested that MT-ATP6 methylation mediated the significant association of urinary 1-OHP with FEV1/FVC. Our findings suggested the methylation of platelet mitochondrial gene MT-ATP6 and FEV1/FVC to be negatively associated with PM exposure. Platelet mtDNA methylation acted as an intermediary between PAH exposure and lung function decline. The mitochondrial epigenetic regulation in platelets, in response to PM exposure, might be involved in subsequent progress of abnormal pulmonary function.

Lung function impairment and risk of incident heart failure: the NHLBI Pooled Cohorts Study.

The aim is to evaluate associations of lung function impairment with risk of incident heart failure (HF). Data were pooled across eight US population-based cohorts that enrolled participants from 1987 to 2004. Participants with self-reported baseline cardiovascular disease were excluded. Spirometry was used to define obstructive [forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.70] or restrictive (FEV1/FVC ≥0.70, FVC <80%) lung physiology. The incident HF was defined as hospitalization or death caused by HF. In a sub-set, HF events were sub-classified as HF with reduced ejection fraction (HFrEF; EF <50%) or preserved EF (HFpEF; EF ≥50%). The Fine-Gray proportional sub-distribution hazards models were adjusted for sociodemographic factors, smoking, and cardiovascular risk factors. In models of incident HF sub-types, HFrEF, HFpEF, and non-HF mortality were treated as competing risks. Among 31 677 adults, there were 3344 incident HF events over a median follow-up of 21.0 years. Of 2066 classifiable HF events, 1030 were classified as HFrEF and 1036 as HFpEF. Obstructive [adjusted hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.07-1.27] and restrictive physiology (adjusted HR 1.43, 95% CI 1.27-1.62) were associated with incident HF. Obstructive and restrictive ventilatory defects were associated with HFpEF but not HFrEF. The magnitude of the association between restrictive physiology and HFpEF was similar to associations with hypertension, diabetes, and smoking. Lung function impairment was associated with increased risk of incident HF, and particularly incident HFpEF, independent of and to a similar extent as major known cardiovascular risk factors.

Pulmonary function, exercise capacity and dyspnea in patients 7 ​years after Nuss surgery

PurposePectus excavatum is a frequent thoracic malformation increasingly treated with minimally invasive methods (MIRPE), which are performed for cardio-respiratory problems and in some centers also for esthetic considerations. Theoretically, MIRPE may increase thoracic elastic recoil, work of breathing and cause emphysema. The aim of the present study was to determine whether teenagers who underwent MIRPE may expect normal thoracic cage development, cardio-respiratory function, exercise capacity and asymptomatic functioning. Material and methodsFifty five patients (21.1 ​± ​3.0 years) who underwent MIRPE between 2000 and 2010 were assessed 6.8 (±2.4) years after surgery. Controls were matched for sex, age and height to the intervention participants. Spirometry, body plethysmography, diffusion capacity and the 6 ​min walking test (6MWT) were performed. Anteroposterior (AP) and transverse chest diameters were measured. ResultsParticipants who underwent MIRPE had normal pulmonary function, and exercise capacity. After adjustment for potential confounders, the intervention group had lower mean BMI [–1.88 ​± ​0.56 (kg/m2); p ​= ​0.001] and chest AP diameter [-2.79 ​± ​0.57 (cm); p ​< ​0.001], but higher residual volume (RV%) [12.98 ​± ​5.31 (%); p ​= ​0.001], RV% total lung capacity (TLC) [5.56 ​± ​0.92 (%); p ​< ​0.001], forced expiratory volume in 1 ​s/forced vital capacity (FEV1/FVC) [2.64 ​± ​1.28 (%); p ​= ​0.039] and 6MWT distance [29.10 ​± ​13.02 (m); p ​= ​0.025]. ConclusionsYoung adults who undergo MIRPE may expect normal pulmonary function and exercise capacity. Observed differences in air trapping require further assessment in terms of emphysema development risk.

Characteristics and Prevalence of Early Chronic Obstructive Pulmonary Disease in a Middle-Aged Population: Results from a Nationwide-Representative Sample.

IntroductionFew studies have examined the prevalence and associated factors of early chronic obstructive pulmonary disease (COPD) in Asians.ObjectiveTo evaluate the prevalence of early COPD and its associated factors among non-institutionalized middle-aged Korean adults.MethodsA total of 3195 participants aged 40–49 years from the 2016–2018 Korea National Health and Nutrition Examination Survey were included in this study. Patients (1) aged less than 50 years, (2) with a minimum of 10 pack-years of smoking, and (3) with forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) below the lower limit of normal were diagnosed with early COPD. The prevalence and odds ratio (OR) for early COPD were measured using multivariate logistic regression analysis, and the demographic data, anthropometric measurements, socioeconomic status, and lifestyle factors were considered covariates.ResultsThe overall prevalence of early COPD among the middle-aged Korean population was 2.4% (4.4% in men and 0.4% in women), while that in participants with ≥10 pack-years was 8.2% (8.1% in men and 11.3% in women). A multivariate logistic regression model showed that male sex, urban residence, chronic sputum production, and hypertriglyceridemia were associated with increased ORs for early COPD in middle-aged, non-institutionalized Korean adults.ConclusionEarly COPD is prevalent among middle-aged smokers in Korea. Efforts are needed to reduce the potential negative effects of early COPD on public health in Korea and other Asian countries.

Clinical Evaluation for Sublingual Immunotherapy With Dermatophagoides farinae in Polysensitized Allergic Asthma Patients.

Background: Many studies have demonstrated the efficacy of single-allergen sublingual immunotherapy (SLIT) in polysensitized patients with allergic rhinitis (AR), but less is reported in polysensitized patients with allergic asthma (AS).Method: Data of 133 adult patients with house dust mite (HDM)-induced AS who had been treated for 3 years were collected. These patients were divided into the control group (treated with low to moderate dose of inhaled glucocorticoids and long-acting β2 agonists, n = 37) and the SLIT group (further treated with Dermatophagoides farinae drops, n = 96). The SLIT group contained three subgroups: the single-allergen group (only sensitized to HDM, n = 35), the 1- to 2-allergen group (HDM combined with one to two other allergens, n = 32), and the 3-or-more-allergen group (HDM combined with three or more other allergens, n = 29). The total asthma symptom score (TASS), total asthma medicine score (TAMS), and asthma control test (ACT) were assessed before treatment and at yearly visits. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) was assessed before treatment and at the end of SLIT.Results: TASS and ACT scores in the control group were significantly higher than that in the single-allergen group and the 1- to 2-allergen group after 1, 2, and 3 years of SLIT and significantly higher than that in the 3-or-more-allergen group after 3-year SLIT (all p < 0.05). TAMS of the control group was significantly higher than that of the other three groups after 0.5, 1, 2, and 3 years of SLIT (all p < 0.05). FEV1/FVC in the control group was significantly higher than baseline after 3 years of immunotherapy (p < 0.05).Conclusion: Patients sensitized to HDM with/without other allergens showed similar efficacy after 3 years of SLIT. However, the initial response of patients with three or more allergens was slower during immunotherapy process.

Computed tomography total airway count predicts progression to COPD in at-risk smokers.

There is limited understanding of how to identify people at high risk of developing COPD. Our objective was to investigate the association between computed tomography (CT) total airway count (TAC) and incident COPD over 3 years among ever-smokers from the population-based Canadian Cohort Obstructive Lung Disease (CanCOLD) study.CT and spirometry were acquired in ever-smokers at baseline; spirometry was repeated at 3-year follow-up. CT TAC was generated by summing all airway segments in the segmented airway tree (VIDA Diagnostics, Inc.). CT airway wall area, wall thickness for a theoretical airway with 10 mm perimeter (Pi10), and low attenuation areas below −856 HU (LAA856) were also measured. Logistic and mixed effects regression models were constructed to determine the association for CT measurements with development of COPD and forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) decline, respectively.Among 316 at-risk participants evaluated at baseline (65±9 years, 40% female, 18±19 pack-years), incident COPD was detected in 56 participants (18%) over a median 3.1±0.6 years of follow-up. Among CT measurements, only TAC was associated with incident COPD (p=0.03), where a 1-sd decrement in TAC increased the odds ratio for incident COPD by a factor of two. In a multivariable linear regression model, reduced TAC was significantly associated with greater longitudinal FEV1/FVC decline (p=0.03), but no other measurements were significant.CT TAC predicts incident COPD in at-risk smokers, indicating that smokers exhibit early structural changes associated with COPD prior to abnormal spirometry.