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1.
Eur J Endocrinol ; 184(2): 289-298, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33513126

RESUMO

Background: Diabetes mellitus is an established risk factor for cardiovascular diseases. Even impaired levels of glucose and insulin might harm organ function prior to diabetes onset. Whether serum glucose or insulin plays a direct role in cardiac dysfunction or lung volume reduction remains unclear. The aim was to investigate the relationship between glucose and insulin with the right ventricle and lung volumes within KORA-MRI FF4 study. Methods: From the KORA-MRI FF4 cohort study 337 subjects (mean age 55.7 ± 9.1 years; 43% women) underwent a whole-body 3T MRI scan. Cardiac parameters derived from a cine-steady-state free precession sequence using cvi42. MRI-based lung volumes derived semi-automatically using an in-house algorithm. Fasting serum glucose, fasting insulin levels, and HOMA index were calculated in all study subjects. Linear regression analyses were performed to assess the relationships between glucose and insulin levels with right ventricle volumes and lung volumes adjusted for age, sex, BMI, and cardiovascular risk factors. Results: In univariate and multivariate-adjusted models, high serum insulin was inversely associated with end-diastolic volume (ß = -12.43, P < 0.001), end-systolic volume (ß = -7.12, P < 0.001), stroke volume (ß = -5.32, P < 0.001), but not with ejection fraction. The association remained significant after additional adjustment for lung volumes. Similarly, serum insulin was inversely associated with lung volume (ß = -0.15, P = 0.04). Sensitivity analysis confirmed results after excluding subjects with known diabetes. Conclusions: Serum insulin was inversely associated with right ventricle function and lung volumes in subjects from the general population free of cardiovascular disease, suggesting that increased insulin levels may contribute to subclinical cardiopulmonary circulation impairment.


Assuntos
Insulina/sangue , Pulmão/patologia , Função Ventricular Direita/fisiologia , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Feminino , Alemanha , Testes de Função Cardíaca , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Medidas de Volume Pulmonar , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Fatores de Risco
2.
Occup Environ Med ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115922

RESUMO

OBJECTIVES: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project. METHODS: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens. RESULTS: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0). CONCLUSIONS: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.

3.
Respir Med ; 171: 106087, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32917358

RESUMO

BACKGROUND: Guidelines for chronic obstructive pulmonary disease (COPD) recommend supplementing pharmacotherapy with non-pharmacological interventions. Little is known about the use of such interventions by patients. We analyzed the utilization of a number of non-pharmacological interventions and identified potential determinants of use. METHODS: Based on self-reports, use of interventions (smoking cessation, influenza vaccination, physiotherapy, sports program, patient education, pulmonary rehabilitation) and recommendation to use were assessed in 1410 patients with COPD. The utilization was analyzed according to sex and severity of disease. Potential determinants of utilization included demographic variables and disease characteristics and were analyzed using logistic regression models. RESULTS: Influenza vaccination in the previous autumn/winter was reported by 73% of patients. About 19% were currently participating in a reimbursed sports program, 10% received physiotherapy, 38% were ever enrolled in an educational program, and 34% had ever participated in an outpatient or inpatient pulmonary rehabilitation program. Out of 553 current or former smokers, 24% had participated in a smoking cessation program. While reports of having received a recommendation to use mainly did not differ according to sex, women showed significantly (p < 0.05) higher utilization rates than men for all interventions except influenza vaccination. Smoking was a predictor for not having received a recommendation for utilization and also significantly associated with a reduced odds of utilization. We found a correlation between recommendation to use and utilization. CONCLUSIONS: Utilization of non-pharmacological interventions was lower in men and smokers. A recommendation or offer to use by the physician could help to increase uptake.

4.
Aging (Albany NY) ; 12(16): 16539-16554, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747609

RESUMO

Chronic obstructive pulmonary disease (COPD) is a frequent diagnosis in older individuals and contributor to global morbidity and mortality. Given the link between lung disease and aging, we need to understand how molecular indicators of aging relate to lung function and disease. Using data from the population-based KORA (Cooperative Health Research in the Region of Augsburg) surveys, we associated baseline epigenetic (DNA methylation) age acceleration with incident COPD and lung function. Models were adjusted for age, sex, smoking, height, weight, and baseline lung disease as appropriate. Associations were replicated in the Normative Aging Study. Of 770 KORA participants, 131 developed incident COPD over 7 years. Baseline accelerated epigenetic aging was significantly associated with incident COPD. The change in age acceleration (follow-up - baseline) was more strongly associated with COPD than baseline aging alone. The association between the change in age acceleration between baseline and follow-up and incident COPD replicated in the Normative Aging Study. Associations with spirometric lung function parameters were weaker than those with COPD, but a meta-analysis of both cohorts provide suggestive evidence of associations. Accelerated epigenetic aging, both baseline measures and changes over time, may be a risk factor for COPD and reduced lung function.

5.
Dtsch Med Wochenschr ; 145(16): 1174-1178, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32791555

RESUMO

In case of obstructive, interstitial and malignant respiratory and lung diseases, occupational causes must always be searched for. The sensitivity and specificity of specific IgE determinations in the diagnosis of occupational asthma are only slightly above 70 %, even for high-molecular allergens. If the patient's medical history is positive, further diagnostics must be carried out, if necessary up to specific exposure testing in specialised institutions. New data show that the serial FeNO determination after working days compared to days off contains additional information that can lead to a positive diagnostic classification. In case of interstitial lung diseases, (avoidable) occupational triggers must be searched for - a new questionnaire provides practical assistance. Patients with lung carcinoma should also be investigated for occupational causes. Here too, questionnaires and tables are available in simple language. In future lung cancer caused by long-term exposure to passive smoke will be considered an occupational disease.

6.
BMC Pulm Med ; 20(1): 148, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32471493

RESUMO

BACKGROUND: Forced expiratory volume in one second (FEV1) characterizes the pathophysiology of COPD and different trajectories of FEV1 decline have been observed in patients with COPD (e.g. gradual or episodic). There is limited information about the development of patient-reported health-related quality of life (HRQL) over the full range of the natural history of COPD. We examined the longitudinal association between change in FEV1 and change in disease-specific and generic HRQL. METHODS: We analysed data of 1734 patients with COPD participating in the COSYCONET cohort with up to 3 years of follow-up. Patients completed the Saint George's Respiratory Questionnaire (SGRQ) and the EQ-5D Visual Analog Scale (EQ VAS). Change score models were used to investigate the relationship between HRQL and FEV1 and to calculate mean changes in HRQL per FEV1 change categories [decrease (≤ - 100 ml), no change, increase (≥ 100 ml)] after 3 years. Applying hierarchical linear models (HLM), we estimated the cross-sectional between-subject difference and the longitudinal within-subject change of HRQL as related to a FEV1 difference or change. RESULTS: We observed a statistically significant deterioration in SGRQ (total score + 1.3 units) after 3 years, which was completely driven by the activity component (+ 4 units). No significant change was found for the generic EQ VAS. Over the same period, 58% of patients experienced a decrease in FEV1, 28% were recorded as no change in FEV1, and 13% experienced an increase. The relationship between HRQL and FEV1 was found to be approximately linear with decrease in FEV1 being statistically significantly associated with a deterioration in SGRQ (+ 3.20 units). Increase in FEV1 was associated with improvements in SGRQ (- 3.81 units). The associations between change in FEV1 and the EQ VAS were similar. Results of the HLMs were consistent and highly statistically significant, indicating cross-sectional and longitudinal associations. The largest estimates were found for the association between FEV1 and the SGRQ activity domain. CONCLUSIONS: Difference and change in FEV1 over time correlate with difference and change in disease-specific and generic HRQL. We conclude, that deterioration of HRQL should induce timely re-examination of physical status and lung function and possibly reassessment of therapeutic regimes. TRIAL REGISTRATION: NCT01245933. Date of registration: 18 November 2010.

7.
Am J Respir Crit Care Med ; 202(3): 412-421, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32330394

RESUMO

Rationale: Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype.Objectives: We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks.Methods: Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed.Measurements and Main Results: Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated (P trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated (P trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes.Conclusions: Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.


Assuntos
Adenocarcinoma de Pulmão/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Dióxido de Silício , Silicose/epidemiologia , Adulto , Idoso , Canadá/epidemiologia , Fumar Cigarros , Europa (Continente)/epidemiologia , Feminino , Humanos , Exposição por Inalação , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
8.
Am J Respir Crit Care Med ; 202(3): 402-411, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32330395

RESUMO

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes.Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations.Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men.Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 µg/m3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined.Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.


Assuntos
Adenocarcinoma de Pulmão/epidemiologia , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Fumar Cigarros/epidemiologia , Neoplasias Pulmonares/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Emissões de Veículos , Adulto , Idoso , Canadá/epidemiologia , Carbono , Europa (Continente)/epidemiologia , Feminino , Humanos , Exposição por Inalação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores Sexuais
9.
Artigo em Alemão | MEDLINE | ID: mdl-32125462

RESUMO

BACKGROUND: Asthma is one of the most common chronic diseases in both children and adults. Asthma first occurring in adulthood (adult-onset asthma, AOA) is associated with poorer prognosis compared to childhood-onset asthma (COA), which urgently calls for more research in this area. The aim of this work was to analyze the data on asthma collected in the German National Cohort and compare it with the German Health Interview and Examination Survey for Adults (DEGS), in particular regarding AOA. MATERIAL AND METHODS: Our analysis was based on the dataset of the main questionnaire at mid-term of the German National Cohort baseline examination, comprising 101,723 participants. Variables considered in the analyses were self-reported diagnosis of asthma, age at first diagnosis, asthma treatment in the past 12 months, age, and sex. RESULTS: In the midterm dataset, 8.7% of women and 7.0% of men in the German National Cohort reported that they had ever been diagnosed with asthma. Approximately one third of participants with asthma received their initial diagnosis before their 18th birthday. COA affected 2.2% of women and 2.8% of men, whereas AOA affected 6.5% of women and 4.2% of men. During the previous 12 months, 33% of COA cases and 60% of AOA cases were medically treated. CONCLUSION: The proportion of persons affected by asthma in the German National Cohort, as well as observed patterns regarding age and gender, corresponds to other data sources such as DEGS. However, in our analysis, the proportion of individuals with AOA was higher than described in the literature. The increase in cumulative asthma diagnoses with age is markedly steeper in younger participants, indicating a rising trend over time.


Assuntos
Asma/diagnóstico , Adulto , Fatores Etários , Idade de Início , Asma/epidemiologia , Criança , Doença Crônica , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Inquéritos e Questionários
10.
Artigo em Alemão | MEDLINE | ID: mdl-32078705

RESUMO

BACKGROUND: A nationwide assessment of the respiratory status on the basis of standardized lung function measurements has so far not been available in Germany. The present work describes the lung function tests in the German National Cohort (GNC) and presents initial results based on the GNC Midterm Baseline Dataset. MATERIAL AND METHODS: The assessment of lung function in the GNC comprised spirometry (level 1) and the determination of exhaled nitric oxide (FeNO, level 2). Our quality assurance concept included regular training of lung function test procedures at various GNC sites, interim evaluations of test quality, as well as regular calibration/measurement checks of test equipment. For spirometry, we established a stepwise procedure for offline quality control based on raw flow volume curves. RESULTS: In the present dataset (n = 101,734), spirometry was available for 86,893 study participants and FeNO was available for 15,228 participants. The average (±SD) FEV1 Z score (according to GLI 2012) was -0.321 ± 1.047, the FVC Z score was -0.153 ± 0.941, and the FEV1/FVC Z score was -0.337 ± 0.901. The difference in FEV1/FVC between current smokers and never-smokers increased with age. The average FeNO was 14.2 ÷ 2.0 ppb. Current smoking reduced FeNO levels by 43%, whereas respiratory allergy increased FeNO levels by 16% in nonsmokers. DISCUSSION: The results of spirometry and the FeNO measurements are in the expected range with regard to their distributions and correlates. The GNC provides a valuable basis for future investigations of respiratory health and its determinants as well as research into the prevention of respiratory diseases in Germany.


Assuntos
Testes Respiratórios , Asma , Expiração , Alemanha , Humanos , Espirometria
11.
Indoor Air ; 30(3): 396-421, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31944398

RESUMO

Many studies have shown that the use of laser printing devices (LPDs) contributes to the release of particles into the indoor environment. However, after more than two decades of research, the physicochemical properties of LPD-emitted particles and the possible health effects from exposure to particles are still heavily debated. We therefore carried out a critical review of the published studies around emissions and health effects of LPD-emitted particles, aiming at elucidating the nature of these particles and their potential health risks. Realizing the varying methodologies of the studies, a classification of the reviewed studies is adopted, resulting in three categories of emission studies (chamber experiment, office/room measurement, and photocopy shop measurement), and three types of health studies (in vitro/animal studies, human studies in the real world, and human studies in controlled settings). The strengths and limitations of each type of study are discussed in-depth, which in turn helps to understand the cause of divergent results. Overall, LPD-emitted particles are mainly condensed or secondary-formed semi-volatile organic compounds (SVOCs), while solid toner particles account for a very small fraction. The health risk from exposure to LPD-emitted particles is small compared with the health risk from exposure to ambient particles.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Impressão , Compostos Orgânicos Voláteis , Poluentes Atmosféricos , Humanos , Tamanho da Partícula , Material Particulado
12.
Int J Chron Obstruct Pulmon Dis ; 14: 1423-1439, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308648

RESUMO

Background: In light of overall increasing healthcare expenditures, it is mandatory to study determinants of future costs in chronic diseases. This study reports the first longitudinal results on healthcare utilization and associated costs from the German chronic obstructive pulmonary disease (COPD) cohort COSYCONET. Material and methods: Based on self-reported data of 1904 patients with COPD who attended the baseline and 18-month follow-up visits, direct costs were calculated for the 12 months preceding both examinations. Direct costs at follow-up were regressed on baseline disease severity and other co-variables to identify determinants of future costs. Change score models were developed to identify predictors of cost increases over 18 months. As possible predictors, models included GOLD grade, age, sex, education, smoking status, body mass index, comorbidity, years since COPD diagnosis, presence of symptoms, and exacerbation history. Results: Inflation-adjusted mean annual direct costs increased by 5% (n.s., €6,739 to €7,091) between the two visits. Annual future costs were significantly higher in baseline GOLD grades 2, 3, and 4 (factors 1.24, 95%-confidence interval [1.07-1.43], 1.27 [1.09-1.48], 1.57 [1.27-1.93]). A history of moderate or severe exacerbations within 12 months, a comorbidity count >3, and the presence of dyspnea and underweight were significant predictors of cost increase (estimates ranging between + €887 and + €3,679, all p<0.05). Conclusions: Higher GOLD grade, comorbidity burden, dyspnea and moderate or severe exacerbations were determinants of elevated future costs and cost increases in COPD. In addition we identified underweight as independent risk factor for an increase in direct healthcare costs over time.


Assuntos
Custos de Cuidados de Saúde , Gastos em Saúde , Avaliação de Processos e Resultados em Cuidados de Saúde/economia , Doença Pulmonar Obstrutiva Crônica/economia , Doença Pulmonar Obstrutiva Crônica/terapia , Idoso , Assistência Ambulatorial , Comorbidade , Progressão da Doença , Dispneia/economia , Dispneia/epidemiologia , Dispneia/terapia , Feminino , Alemanha/epidemiologia , Custos Hospitalares , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Qualidade de Vida , Fatores de Risco , Índice de Gravidade de Doença , Magreza/economia , Magreza/epidemiologia , Magreza/terapia , Fatores de Tempo , Resultado do Tratamento
14.
Metabolites ; 9(4)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939782

RESUMO

Determination of metabolomic signatures of pulmonary function and chronic obstructive pulmonary disease (COPD) in the general population could aid in identification and understanding of early disease processes. Metabolome measurements were performed on serum from 4742 individuals (2354 African-Americans and 1529 European-Americans from the Atherosclerosis Risk in Communities study and 859 Europeans from the Cooperative Health Research in the Region of Augsburg study). We examined 368 metabolites in relation to cross-sectional measures of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), their ratio (FEV1/FVC) and COPD using multivariable regression followed by meta-analysis. At a false discovery rate of 0.05, 95 metabolites were associated with FEV1 and 100 with FVC (73 overlapping), including inverse associations with branched-chain amino acids and positive associations with glutamine. Ten metabolites were associated with FEV1/FVC and seventeen with COPD (393 cases). Enriched pathways of amino acid metabolism were identified. Associations with FEV1 and FVC were not driven by individuals with COPD. We identified novel metabolic signatures of pulmonary function and COPD in African and European ancestry populations. These may allow development of biomarkers in the general population of early disease pathogenesis, before pulmonary function has decreased to levels diagnostic for COPD.

15.
Nat Genet ; 51(3): 481-493, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30804560

RESUMO

Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.


Assuntos
Predisposição Genética para Doença/genética , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Fumar/genética
16.
Eur Radiol ; 29(3): 1595-1606, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30151641

RESUMO

OBJECTIVES: Whole-body MR imaging is increasingly utilised; although for lung dedicated sequences are often not included, the chest is typically imaged. Our objective was to determine the clinical utility of lung volumes derived from non-dedicated MRI sequences in the population-based KORA-FF4 cohort study. METHODS: 400 subjects (56.4 ± 9.2 years, 57.6% males) underwent whole-body MRI including a coronal T1-DIXON-VIBE sequence in inspiration breath-hold, originally acquired for fat quantification. Based on MRI, lung volumes were derived using an automated framework and related to common predictors, pulmonary function tests (PFT; spirometry and pulmonary gas exchange, n = 214) and obstructive lung disease. RESULTS: MRI-based lung volume was 4.0 ± 1.1 L, which was 64.8 ± 14.9% of predicted total lung capacity (TLC) and 124.4 ± 27.9% of functional residual capacity. In multivariate analysis, it was positively associated with age, male, current smoking and height. Among PFT indices, MRI-based lung volume correlated best with TLC, alveolar volume and residual volume (RV; r = 0.57 each), while it was negatively correlated to FEV1/FVC (r = 0.36) and transfer factor for carbon monoxide (r = 0.16). Combining the strongest PFT parameters, RV and FEV1/FVC remained independently and incrementally associated with MRI-based lung volume (ß = 0.50, p = 0.04 and ß = - 0.02, p = 0.02, respectively) explaining 32% of the variability. For the identification of subjects with obstructive lung disease, height-indexed MRI-based lung volume yielded an AUC of 0.673-0.654. CONCLUSION: Lung volume derived from non-dedicated whole-body MRI is independently associated with RV and FEV1/FVC. Furthermore, its moderate accuracy for obstructive lung disease indicates that it may be a promising tool to assess pulmonary health in whole-body imaging when PFT is not available. KEY POINTS: • Although whole-body MRI often does not include dedicated lung sequences, lung volume can be automatically derived using dedicated segmentation algorithms • Lung volume derived from whole-body MRI correlates with typical predictors and risk factors of respiratory function including smoking and represents about 65% of total lung capacity and 125% of the functional residual capacity • Lung volume derived from whole-body MRI is independently associated with residual volume and the ratio of forced expiratory volume in 1 s to forced vital capacity and may allow detection of obstructive lung disease.


Assuntos
Medidas de Volume Pulmonar , Imagem por Ressonância Magnética , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória , Idoso , Algoritmos , Estudos de Casos e Controles , Feminino , Volume Expiratório Forçado , Humanos , Processamento de Imagem Assistida por Computador , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Volume Residual , Fumar/efeitos adversos , Fumar/fisiopatologia , Espirometria , Capacidade Pulmonar Total , Capacidade Vital
17.
Epigenetics ; 13(10-11): 1039-1055, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30343628

RESUMO

DNA methylation is an epigenetic regulator of gene transcription, which has been found to be both metastable and variable within human cohort studies. Currently, few studies have been done to identify metastable DNA methylation biomarkers associated with longitudinal lung function decline in humans. The identification of such biomarkers is important for screening vulnerable populations. We hypothesized that quantifiable blood-based DNA methylation alterations would serve as metastable biomarkers of lung function decline and aging, which may help to discover new pathways and/or mechanisms related to pulmonary pathogenesis. Using linear mixed models, we performed an Epigenome Wide Association Study (EWAS) between DNA methylation at CpG dinucleotides and longitudinal lung function (FVC, FEV1, FEF25-75%) decline and aging with initial discovery in the Normative Aging Study, and replication in the Cooperative Health Research in the Region of Augsburg cohort. We identified two metastable epigenetic loci associated with either poor lung function and aging, cg05575921 (AHRR gene), or lung function independently of aging, cg06126421 (IER3 gene). These loci may inform basic mechanisms associated with pulmonary function, pathogenesis, and aging. Human epigenomic variation, may help explain features of lung function decline and related pathophysiology not attributable to DNA sequence alone, such as accelerated pulmonary decline in smokers, former smokers, and perhaps non-smokers. Our EWAS across two cohorts, therefore, will likely have implications for the human population, not just the elderly.


Assuntos
Envelhecimento/patologia , Metilação de DNA , Epigênese Genética , Pneumopatias/genética , Pulmão/crescimento & desenvolvimento , Idoso , Envelhecimento/genética , Ilhas de CpG , Feminino , Estudo de Associação Genômica Ampla , Humanos , Pulmão/patologia , Masculino
18.
Wellcome Open Res ; 3: 4, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30175238

RESUMO

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.

19.
Qual Life Res ; 27(3): 735-745, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29411224

RESUMO

PURPOSE: Among patients with lung disease, decreased lung function is associated with lower health-related quality of life. However, whether this association is detectable within the physiological variability of respiratory function in lung-healthy populations is unknown. We analyzed the association of each EQ-5D-3L dimension (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and self-reported physical inactivity with spirometric indices in lung-healthy adults. Modulating effects between inactivity and EQ-5D dimensions were considered. METHODS: 1132 non-smoking, apparently lung-healthy participants (48% male, aged 64 ± 12 years) from the population-based KORA F4L and Age surveys in Southern Germany were analyzed. Associations of each EQ-5D dimension and inactivity with spirometric indices serving as outcomes (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and mid-expiratory flow) were examined by linear regression, considering possible confounders. Interactions between EQ-5D dimensions (no problems/any problems) and inactivity (four categories of time spent engaging in exercise: inactive to most active) were assessed. RESULTS: Among all participants 42% reported no problems in any EQ-5D dimension, 24% were inactive and 32% exercised > 2 h/week. After adjustment, FEV1 was - 99 ml (95% CI - 166; - 32) and FVC was - 109 ml (95% CI - 195; - 24) lower among subjects with mobility problems. Comparable estimates were observed for usual activities. Inactivity was negatively associated with FVC (ß-coefficient: - 83 ml, 95% CI - 166; 0), but showed no interactions with EQ-5D. CONCLUSIONS: Problems with mobility or usual activities, and inactivity were associated with slightly lower spirometric parameters in lung-healthy adults, suggesting a relationship between perceived physical functioning and volumetric lung function.


Assuntos
Pulmão/fisiologia , Qualidade de Vida/psicologia , Testes de Função Respiratória/métodos , Espirometria/métodos , Idoso , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
20.
BMC Pulm Med ; 18(1): 27, 2018 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29409487

RESUMO

BACKGROUND: The relationship of spirometric values to other respiratory and functional parameters in advanced age is not well studied. We assessed this relationship in elderly subjects with either good or poor spirometric parameters to reveal whether different domains of lung function show comparable differences between the two groups. METHODS: Among subjects of the population-based KORA-Age cohort (n = 935, 65-90y; 51% male) two groups were selected from either the lower (LED; n = 51) or the upper (UED; n = 72) end of the FEV1 distribution. All subjects did not have a history of lung disease and were non-smokers at the time of the study. Measurements included spirometry, body plethysmography, diffusing capacity for NO and CO, respiratory pump function and exhaled NO (FeNO). In addition, 6-min walking distance as a functional overall measure, as well as telomere length of blood leukocytes and serum 8-hydroxydeoxyguanosine (8-OHdG) as potential markers of overall biological ageing and stress were determined. RESULTS: In the majority of parameters, LED subjects showed significantly impaired values compared to UED subjects. Differences in spirometric parameters, airway resistance and respiratory pump function ranged between 10% and more than 90% in terms of predicted values. In contrast, volume-related CO and NO diffusing capacity showed differences between groups of lower than 5%, while telomere length, 8-OHdG and FeNO were similar. This was reflected in the differences in "functional age" as derived from prediction equations. CONCLUSIONS: In elderly subjects without a history of lung disease differences in spirometric parameters were associated with differences in other lung-mechanical parameters including body plethysmography but not with differences in volume-corrected gas exchange measures. Thus, the concept of a general "lung age" as suggested by the widespread use of this term in connection with spirometry should be considered with caution.


Assuntos
Envelhecimento/fisiologia , Pulmão/fisiopatologia , 8-Hidroxi-2'-Desoxiguanosina , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Envelhecimento/metabolismo , Testes Respiratórios , Monóxido de Carbono , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Feminino , Volume Expiratório Forçado , Humanos , Leucócitos/metabolismo , Masculino , Óxido Nítrico , Pletismografia Total , Capacidade de Difusão Pulmonar , Telômero/metabolismo , Teste de Caminhada
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