Emphysema-Predominant COPD Had a Greater 5-Year Mortality and a Worse Annual Decline in Lung Function Than Airway Obstruction-Predominant COPD or Asthma at Initial Same Degree of Airflow Obstruction.
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ABSTRACT:
SUBMITTER: Lin CW
PROVIDER: S-EPMC8622286 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chronic obstructive pulmonary disease (COPD) is a major public health problem with increasing prevalence worldwide. The primary aim of this study was to identify genes and gene ontologies associated with COPD severity. Gene expression profiling was performed on total RNA extracted from lung tissue of 18 former smokers with COPD. Class comparison analysis on mild (n?=?9, FEV(1) 80-110% predicted) and moderate (n?=?9, FEV(1) 50-60% predicted) COPD patients identified 46 differentially expressed genes (p<0.01), of which 14 genes were technically confirmed by quantitative real-time-PCR. Biological replication in an independent test set of 58 lung samples confirmed the altered expression of ten genes with increasing COPD severity, with eight of these genes (NNMT, THBS1, HLA-DPB1, IGHD, ETS2, ELF1, PTGDS and CYRBD1) being differentially expressed by greater than 1.8 fold between mild and moderate COPD, identifying these as candidate determinants of COPD severity. These genes belonged to ontologies potentially implicated in COPD including angiogenesis, cell migration, proliferation and apoptosis. Our secondary aim was to identify gene ontologies common to airway obstruction, indicated by impaired FEV(1) and KCO. Using gene ontology enrichment analysis we have identified relevant biological and molecular processes including regulation of cell-matrix adhesion, leukocyte activation, cell and substrate adhesion, cell adhesion, angiogenesis, cell activation that are enriched among genes involved in airflow obstruction. Exploring the functional significance of these genes and their gene ontologies will provide clues to molecular changes involved in severity of COPD, which could be developed as targets for therapy or biomarkers for early diagnosis.
| S-EPMC3057973 | biostudies-literature
Project description:BackgroundVery severe chronic obstructive pulmonary disease causes cor pulmonale with elevated pulmonary vascular resistance and secondary reductions in left ventricular filling, stroke volume, and cardiac output. We hypothesized that emphysema, as detected on computed tomography (CT), and airflow obstruction are inversely related to left ventricular end-diastolic volume, stroke volume, and cardiac output among persons without very severe lung disease.MethodsWe measured left ventricular structure and function with the use of magnetic resonance imaging in 2816 persons who were 45 to 84 years of age. The extent of emphysema (expressed as percent emphysema) was defined as the percentage of voxels below -910 Hounsfield units in the lung windows on cardiac computed tomographic scans. Spirometry was performed according to American Thoracic Society guidelines. Generalized additive models were used to test for threshold effects.ResultsOf the study participants, 13% were current smokers, 38% were former smokers, and 49% had never smoked. A 10-point increase in percent emphysema was linearly related to reductions in left ventricular end-diastolic volume (-4.1 ml; 95% confidence interval [CI], -3.3 to -4.9; P<0.001), stroke volume (-2.7 ml; 95% CI, -2.2 to -3.3; P<0.001), and cardiac output (-0.19 liters per minute; 95% CI, -0.14 to -0.23; P<0.001). These associations were of greater magnitude among current smokers than among former smokers and those who had never smoked. The extent of airflow obstruction was similarly associated with left ventricular structure and function, and smoking status had similar modifying effects on these associations. Percent emphysema and airflow obstruction were not associated with the left ventricular ejection fraction.ConclusionsIn a population-based study, a greater extent of emphysema on CT scanning and more severe airflow obstruction were linearly related to impaired left ventricular filling, reduced stroke volume, and lower cardiac output without changes in the ejection fraction.
| S-EPMC2887729 | biostudies-literature
Project description:Airflow obstruction is an independent risk factor for cardiovascular events in the general population. The affected vascular bed and contribution of emphysema to cardiovascular risk are unclear. We examined whether an obstructive pattern of spirometry and quantitatively defined emphysema were associated with subclinical atherosclerosis in the carotid, peripheral and coronary circulations. The Multi-Ethnic Study of Atherosclerosis recruited participants aged 45-84 yrs without clinical cardiovascular disease. Spirometry, carotid intima-media thickness (IMT), ankle-brachial index (ABI) and coronary artery calcium (CAC) were measured using standard protocols. Percentage of emphysema-like lung was measured in the lung windows of cardiac computed tomography scans among 3,642 participants. Multiple linear regression was used to adjust for cardiac risk factors, including C-reactive protein. Decrements in forced expiratory volume in 1 s (FEV(1)) and FEV(1)/forced vital capacity ratio were associated with greater internal carotid IMT, particularly among smokers (p=0.03 and p<0.001, respectively) whereas percentage emphysema was associated with reduced ABI regardless of smoking history (p=0.004). CAC was associated with neither lung function (prevalence ratio for the presence of CAC in severe airflow obstruction 0.99, 95% CI 0.91-1.07) nor percentage emphysema. An obstructive pattern of spirometry and emphysema were associated distinctly and independently with subclinical atherosclerosis in the carotid arteries and peripheral circulation, respectively, and were not independently related to CAC.
| S-EPMC3616898 | biostudies-literature
Project description:RationaleTo study the relationship between emphysema and/or airflow obstruction and lung cancer in a high-risk population.ObjectiveWe studied lung cancer related to radiographic emphysema and spirometric airflow obstruction in tobacco-exposed persons who were screened for lung cancer using chest computed tomography (CT).MethodsSubjects completed questionnaires, spirometry, and low-dose helical chest CT. CT scans were scored for emphysema based on National Emphysema Treatment Trial criteria. Multiple logistic regressions estimated the independent associations between various factors, including radiographic emphysema and airflow obstruction, and subsequent lung cancer diagnosis.Measurements and main resultsAmong 3,638 subjects, 57.5, 18.8, 14.6, and 9.1% had no, trace, mild, and moderate-severe emphysema, and 57.3, 13.6, 22.8, and 6.4% had no, mild (Global Initiative for Chronic Obstructive Lung Disease [GOLD] I), moderate (GOLD II), and severe (GOLD III-IV) airflow obstruction. Of 3,638 subjects, 99 (2.7%) received a lung cancer diagnosis. Adjusting for sex, age, years of cigarette smoking, and number of cigarettes smoked daily, logistic regression showed the expected lung cancer association with the presence of airflow obstruction (GOLD I-IV, odds ratio [OR], 2.09; 95% confidence interval [CI], 1.33-3.27). A second logistic regression showed lung cancer related to emphysema (OR, 3.56; 95% CI, 2.21-5.73). After additional adjustments for GOLD class, emphysema remained a strong and statistically significant factor related to lung cancer (OR, 3.14; 95% CI, 1.91-5.15).ConclusionsEmphysema on CT scan and airflow obstruction on spirometry are related to lung cancer in a high-risk population. Emphysema is independently related to lung cancer. Both radiographic emphysema and airflow obstruction should be considered when assessing lung cancer risk.
| S-EPMC2556456 | biostudies-literature
Project description:PurposeLimited data exist describing risk factors for mortality in patients having predominantly emphysema.Subjects and methodsA total of 609 patients with severe emphysema (ages 40-83 yr; 64.2% male) randomized to the medical therapy arm of the National Emphysema Treatment Trial formed the study group. Cox proportional hazards regression analysis was used to investigate risk factors for all-cause mortality. Risk factors examined included demographics, body mass index, physiologic data, quality of life, dyspnea, oxygen utilization, hemoglobin, smoking history, quantitative emphysema markers on computed tomography, and a modification of a recently described multifunctional index (modified BODE).ResultsOverall, high mortality was seen in this cohort (12.7 deaths per 100 person-years; 292 total deaths). In multivariate analyses, increasing age (p=0.001), oxygen utilization (p=0.04), lower total lung capacity % predicted (p=0.05), higher residual volume % predicted (p=0.04), lower maximal cardiopulmonary exercise testing workload (p=0.002), greater proportion of emphysema in the lower lung zone versus the upper lung zone (p=0.005), and lower upper-to-lower-lung perfusion ratio (p=0.007), and modified BODE (p=0.02) were predictive of mortality. FEV1 was a significant predictor of mortality in univariate analysis (p=0.005), but not in multivariate analysis (p=0.21).ConclusionAlthough patients with advanced emphysema experience significant mortality, subgroups based on age, oxygen utilization, physiologic measures, exercise capacity, and emphysema distribution identify those at increased risk of death.
| S-EPMC2662972 | biostudies-literature
Project description:ObjectiveCT-diagnosed emphysema is associated with poor prognosis in chronic obstructive pulmonary disease (COPD). Its clinical impacts on prognoses of asthma with chronic airflow obstruction (CAO) are not well known. We sought to compare mortalities and prognostic factors in COPD and asthma with CAO by the presence or absence of CT-diagnosed emphysema.DesignRetrospective cohort study.SettingReferral centre hospital for respiratory disease.Participants1272 patients aged over 40 years with CAO (January 2000 to December 2011). CAO was defined as a forced expiratory volume in 1 s/forced vital capacity <0.7 after bronchodilator use throughout the observation period.Primary and secondary outcome measurementsOverall mortality served as the primary endpoint. We compared mortalities and prognostic factors of COPD and asthma subgroups with or without emphysema. Secondary endpoints were the prevalence of COPD and asthma in patients with CAO.ResultsOverall, diagnoses included COPD with emphysema in 517 (40.6%) patients, COPD without emphysema in 104 (8.2%) patients, asthma with emphysema in 178 (13.9%) patients, asthma without emphysema in 169 (13.3%) patients, other respiratory diseases (RD) with emphysema in 128 (10.1%) patients, and other RD without emphysema in 176 (13.8%) patients. Patients with asthma without emphysema had the best prognosis followed by those with asthma with emphysema, COPD without emphysema and COPD with emphysema. Each subgroup had distinct prognostic factors. Presence of emphysema was an independent risk factor for de novo lung cancer among patients with CAO.ConclusionsPatients with asthma with CAO have a better prognosis than patients with COPD. The presence of CT-diagnosed emphysema predicts poor prognosis in COPD and asthma with CAO.
| S-EPMC3822307 | biostudies-literature
Project description:OBJECTIVES:Subglottic stenosis (SGS) is one of the most common airway disorders in pediatric patients. Currently, treatment decisions rely primarily on the Cotton-Myer scale, which classifies SGS severity based on percentage reduction in airspace cross-sectional area (CSA). However, the precise relationship between upper airway resistance and subglottic CSA is unknown. We hypothesize that airway resistance can be described by the Bernoulli Obstruction Theory, which predicts that airway resistance is inversely proportional to airspace CSA ( R∝A-1) in cases of severe constriction. METHODS:Computed tomography (CT) scans of six healthy subjects and five SGS patients were used to create three-dimensional models of the respiratory tract from nostrils to carina. Cylindrical segments of varying lengths and varying diameters were digitally inserted in the subglottis of the healthy subjects to create simulated SGS models. Computational fluid dynamics simulations were run, and airway resistance was computed in the simulated SGS models and actual SGS models. RESULTS:Constriction diameter had a greater impact in airway resistance than constriction length. In agreement with the Bernoulli Obstruction Theory, airway resistance in the simulated SGS models was well represented by the power law R=aAb, where a is a constant and the exponent b ranged from -0.85 to -1.07. The percentage reduction in airflow (QOBSTRUCTIONQHEALTHY) at a constant pressure drop was found to be directly proportional to the percentage reduction in CSA (AOBSTRUCTIONAHEALTHY) in the limit of severe constrictions, namely QOBSTRUCTIONQHEALTHY=kAOBSTRUCTIONAHEALTHY, where k=2.25 ± 0.15. Airway resistances in the simulated SGS models were similar to resistances in models based on CT scans of actual SGS patients, suggesting that our simulated SGS models were representative of airway resistance in actual SGS patients. CONCLUSION:Our computer simulations suggest that the degree of airflow limitation in SGS patients may be estimated based on anatomic measurements alone. Future studies are recommended to test these predictions in larger cohorts. LEVEL OF EVIDENCE:4. Laryngoscope, 128:1551-1557, 2018.
| S-EPMC5967982 | biostudies-literature
Project description:BackgroundCOPD includes the chronic bronchitis (CB) and emphysema phenotypes. Although it is generally assumed that emphysema or chronic airflow obstruction (CAO) is associated with worse quality of life (QOL) than is CB, this assumption has not been tested.MethodsThe current study's analyses from the Lovelace Smokers' Cohort (LSC) were validated in the COPD Gene Cohort (COPDGene). CB without CAO (CB only) was defined as self-reported cough productive of phlegm for ≥ 3 mo/y for 2 consecutive years and postbronchodilator FEV1/FVC ≥ 70%. CAO without CB (CAO only) was defined as a postbronchodilator FEV1/FVC < 70% with no evidence of CB. QOL outcomes were obtained from the St. George's Respiratory Questionnaire (SGRQ) and the 36-Item Short Form Health Survey (SF-36) questionnaires. A priori covariates included age, sex, pack-years of smoking, current smoking, and FEV1.ResultsSmokers with CB without CAO (LSC = 341; COPDGene = 523) were younger and had a greater BMI and less smoking exposure than did those with CAO only (LSC = 302; COPDGene = 2,208). Compared with the latter group, QOL scores were worse for those with CB only. Despite similar SGRQ Activity and SF-36 Role Physical and Physical Functioning, SGRQ Symptoms and Impact scores and SF-36 emotional and social measures were worse in the CB-only group, in both cohorts. After adjustment for covariates, the CB-only group remained a significant predictor for "worse" symptoms and emotional and social measures.ConclusionsTo our knowledge, this analysis is the first to suggest that among subjects with COPD, those with CB only present worse QOL symptoms and mental well-being than do those with CAO only.
| S-EPMC4524327 | biostudies-literature
Project description:Chronic obstructive pulmonary disease (COPD) is heterogeneous, but persistent airflow obstruction (AFO) is fundamental to diagnosis. We studied AFO consistency from initial diagnosis and explored factors associated with absent or inconsistent AFO. This was a retrospective observational study using patient-anonymised routine individual data in Care and Health Information Analytics (CHIA) database. Identifying a prevalent COPD cohort based on diagnostic codes in primary care records, we used serial ratios of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC%) from time of initial COPD diagnosis to assign patients to one of three AFO categories, according to whether all (persistent), some (variable) or none (absent) were <70%. We described respiratory prescriptions over 3 years (2011-2013) and used multivariable logistic regression to estimate odds of absent or variable AFO and potential predictors. We identified 14,378 patients with diagnosed COPD (mean ± SD age 68.8 ± 10.7 years), median (IQR) COPD duration of 60 (25,103) months. FEV1/FVC% was recorded in 12,491 (86.9%) patients: median (IQR) 5 (3, 7) measurements. Six thousand five hundred and fifty (52.4%) had persistent AFO, 4507 (36.1%) variable AFO and 1434 (11.5%) absent AFO. Being female, never smoking, having higher BMI or more comorbidities significantly predicted absent and variable AFO. Despite absent AFO, 57% received long-acting bronchodilators and 60% inhaled corticosteroids (50% and 49%, respectively, in those without asthma). In all, 13.1% of patients diagnosed with COPD had unrecorded FEV1/FVC%; 11.5% had absent AFO on repeated measurements, yet many received inhalers likely to be ineffective. Such prescribing is not evidence based and the true cause of symptoms may have been missed.
| S-EPMC6695394 | biostudies-literature
Project description:Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality within the Veterans Healthcare Administration (VHA) and is frequently under-diagnosed. We developed the Veterans Airflow Screening Questionnaire (VAFOSQ) to improve the identification of Veterans with airflow obstruction (AFO), the most commonly used criterion for the diagnosis of COPD.We created an initial survey with 78 variables that have been associated with AFO. A total of 825 patients in 3 primary care clinics performed spirometry after bronchodilator administration and completed the initial survey. Best sets regression was used to build a model that predicted AFO optimally. A total of 195 of 825 (23.3%) patients had AFO and 7 items positively predicted AFO. When the questionnaire score was greater than 25, the VAFOSQ accurately identified AFO with an area under the receiver operating curve of 0.72. In a prospective validation cohort of 376 participants, the positive predictive value was 32% and negative predictive value 81%. The VAFOSQ is a reliable and valid instrument for the identification of veterans at risk for AFO who would benefit from further evaluation with spirometry and assessment for COPD. The VAFOSQ is straightforward to use and can be easily self-administered and self-scored enabling widespread application within the VHA.
| S-EPMC5556954 | biostudies-literature