Predictors Of Chronic Obstructive Pulmonary Disease Research Articles

Suggestive evidence of genetic association of IL23R polymorphisms with chronic obstructive pulmonary disease risk in the Chinese population.

Chronic obstructive pulmonary disease (COPD) is a worldwide public health problem. Previous genetic association studies have identified several susceptibility loci in the interleukin genes that may participate in the nosogenesis of COPD. This study aimed to evaluate the relationship between IL23R loci and COPD susceptibility in the Chinese population. Agena MassARRAY technology was applied to genotype five single nucleotide polymorphisms (SNPs) in the IL23R gene in 498 COPD patients and 498 healthy people. The association between IL23R SNPs and COPD risk was calculated by logistic regression analysis, with odds ratios and 95% confidence intervals. The false-positive report probability analysis was noteworthy for evaluating the significant results. Also, haplotype analysis was performed among IL23R variants, and multifactor dimensionality reduction analysis was performed to assess the SNP-SNP interactions to predict the risk of COPD. Overall analysis showed that rs7517847 had a significant association with an increased risk of COPD. Age-stratified analysis revealed that rs7517847 was significantly related to an increased risk of COPD in people aged over 68 years old. Sex-stratified analysis illustrated a significant association between rs2295359 and rs7517847 and COPD risk in the female population. The significant association of COPD risk with IL23R SNPs was assessed by false-positive report probability values. Additionally, we observed that the haplotypes AAC and GGA formed by rs2201841, rs12743974 and rs10889677 were associated with a reduced risk of COPD (p = 0.009, p = 0.026). Also, the five-loci interaction model formed by rs2295359, rs7517847, rs2201841, rs12743974 and rs10889677 became the best predictor of COPD, with 10/10 cross-validation consistency and 52.4% testing balance accuracy. The research indicated a remarkable association between IL23R variants and COPD susceptibility in the Chinese population. Larger samples and functional research are required to ascertain the relationship between IL23R variants and COPD susceptibility.

Triglyceride-Glucose Index is a Risk Marker of Incident COPD Events in Women.

PurposeThe triglyceride-glucose index (TyG index) is a marker of insulin resistance and metabolic dysfunction and has the advantage of being universally available. Although recent evidence suggests the TyG index has relevance to respiratory health, there have been no prospective studies assessing its value as a biomarker for chronic lung diseases. We aim to assess the TyG index as a potential risk marker for future incident COPD events in the general population.Patients and MethodsBaseline TyG index was assessed in 28,282 middle-aged men and women without previous history of chronic obstructive pulmonary disease (COPD) from the Malmö Preventive Project (men between 1974 and 1982 and women between 1982 and 1992). All subjects were followed up prospectively, and Cox proportional hazards regression was used to assess incident COPD events according to quartiles of TyG index.ResultsAfter an average of 31 years of follow-up, TyG index was a strong predictor of future COPD events even after adjusting for potential confounders (Q4 (highest TyG index) HR (95% CI): 1.21 (1.09–1.35) vs Q1 (reference), p-trend <0.001). After stratifying by sex, the results remained statistically significant in women only (Q4 vs Q1 HR 1.72 (1.41–2.09)). Additionally, the risk remained significant in a cohort of life-long never smokers (Q4 vs Q1 HR 1.47 (1.08–2.01)).ConclusionA raised TyG index is a novel risk marker of future incident COPD events in women. Insulin resistance as reflected by the TyG index can precede the development of obstructive lung disease and as such may be an easily measurable and useful predictor of COPD in women.

Predictors for detecting chronic respiratory diseases in community surveys: A pilot cross-sectional survey in four South and South East Asian low- and middle-income countries.

BackgroundOur previous scoping review revealed limitations and inconsistencies in population surveys of chronic respiratory disease. Informed by this review, we piloted a cross-sectional survey of adults in four South/South-East Asian low-and middle-income countries (LMICs) to assess survey feasibility and identify variables that predicted asthma or chronic obstructive pulmonary disease (COPD).MethodsWe administered relevant translations of the BOLD-1 questionnaire with additional questions from ECRHS-II, performed spirometry and arranged specialist clinical review for a sub-group to confirm the diagnosis. Using random sampling, we piloted a community-based survey at five sites in four LMICs and noted any practical barriers to conducting the survey. Three clinicians independently used information from questionnaires, spirometry and specialist reviews, and reached consensus on a clinical diagnosis. We used lasso regression to identify variables that predicted the clinical diagnoses and attempted to develop an algorithm for detecting asthma and COPD.ResultsOf 508 participants, 55.9% reported one or more chronic respiratory symptoms. The prevalence of asthma was 16.3%; COPD 4.5%; and ‘other chronic respiratory disease’ 3.0%. Based on consensus categorisation (n = 483 complete records), “Wheezing in last 12 months” and “Waking up with a feeling of tightness” were the strongest predictors for asthma. For COPD, age and spirometry results were the strongest predictors. Practical challenges included logistics (participant recruitment; researcher safety); misinterpretation of questions due to local dialects; and assuring quality spirometry in the field.ConclusionDetecting asthma in population surveys relies on symptoms and history. In contrast, spirometry and age were the best predictors of COPD. Logistical, language and spirometry-related challenges need to be addressed.

Predictors of COPD in symptomatic smokers and ex-smokers seen in primary care.

Even in subjects at high risk of chronic obstructive pulmonary disease (COPD), the diagnosis is often missed due to lack of awareness of symptoms and risk factors. The objective of this study was to identify predictors of a diagnosis of COPD in symptomatic current and ex-smokers seen in a primary care setting. General practitioners (n = 241) consecutively recruited subjects ≥ 35 years, with tobacco exposure, at least one respiratory symptom (i.e. cough, sputum, wheeze, dyspnoea and/or recurrent lower respiratory tract infections), and no previous diagnosis of obstructive airways disease. Information on age, smoking status, body mass index (BMI) and dyspnoea (Medical Research Council (MRC) dyspnoea scale) was obtained. Individuals with airway obstruction (i.e. forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio (FVC) < 0.70) at initial spirometry had a diagnostic spirometry after administration of a bronchodilator. COPD was defined as the presence of symptoms, tobacco exposure and persistent airflow limitation. The most prevalent symptoms were cough (72%) and dyspnoea (48%). Of 3875 (50% females, mean age 57 years) subjects screened, 700 (18.1%) were diagnosed with COPD. Multivariate logistic regression analysis revealed that increasing age 50–59 years (OR 2.4, 95% CI 1.8–3.3), 60–69 years (OR 4.1, 95% CI 3.1–5.5), ≥70 years (OR 5.7, 95% CI 4.2–7.8), BMI < 25 (OR 2.3, 95% CI 1.9–2.7), being current smoker (OR 1.2, 95% CI 1.01–1.5), self-reported dyspnoea (OR 1.7, 95% CI 1.4–2.0), wheeze (OR 1.9, 95% CI 1.5–2.3) and sputum (OR 1.4, 95% CI 1.1–1.7) were associated with a significantly higher risk of being diagnosed with COPD. No association was found between gender, cough and recurrent respiratory tract infections and a diagnosis of COPD. Among symptomatic smokers and ex-smokers seen in primary care, self-reported sputum production, wheeze, dyspnoea and low BMI identify a subgroup with a higher likelihood of COPD.

Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults

ABSTRACTThe genetic and non-genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are still poorly understood. We investigated the potential role of genetic variants of xenobiotic-metabolising enzymes (glutathione-S-transferase M1, GSTM1; glutathione-S-transferase T1, GSTT1; microsomal epoxide hydrolase, mEH), oxidative stress (assessed by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG/creatinine), sex, ageing and smoking habits on susceptibility to development of COPD and its severity in Serbian population. The investigated population consisted of 153 healthy subjects (85 males and 68 females) and 71 patients with COPD (33 males and 38 females). Detection of GSTM1*null, GSTT1*null, mEH Tyr113His and mEH His139Arg gene variants was performed by PCR/RFLP method. Urinary 8-oxodG was determined using HPLC-MS/MS, and expressed as 8-oxodG/creatinine. We revealed that increased urinary 8-oxodG/creatinine and leucocytosis are the strongest independent predictors for COPD development. Increased level of oxidative stress increased the risk for COPD in males [odds ratio (OR), 95% confidence interval (CI): 8.42, 2.26–31.28], more than in females (OR, 95% CI: 3.60, 1.37–9.45). Additionally, independent predictors for COPD were ageing in males (OR, 95% CI: 1.29, 1.12–1.48), while in females they were at least one GSTM1 or GSTT1 gene deletion in combination (OR, 95% CI: 23.67, 2.62–213.46), and increased cumulative cigarette consumption (OR, 95% CI: 1.09, 1.01–1.16). Severity of COPD was associated with the combined effect of low mEH activity phenotype, high level of oxidative stress and heavy smoking. In conclusion, early identification of GSTM1*null or GSTT1*null genotypes in females, low mEH activity phenotype in heavy smokers and monitoring of oxidative stress level can be useful diagnostic and prognostic biomarkers.

Systemic redox imbalance in stable chronic obstructive pulmonary disease

Context: Increased oxidative burden is found in chronic obstructive pulmonary disease (COPD).Objective: To assess the association of ceruloplasmin, albumin, bilirubin, transferrin, thiols and malondialdehyde (MDA) with stable COPD.Materials and methods: Oxidative stress markers measured in 106 COPD patients and 45 healthy subjects were evaluated.Results: Higher ceruloplasmin and MDA, and lower albumin, transferrin and thiols in COPD patients were found. Ceruloplasmin was the strongest single predictor of COPD. The model combining ceruloplasmin, albumin and thiols improved their individual diagnostic performances.Conclusions: Diagnostic characteristics of ceruloplasmin, albumin, transferrin, thiols and MDA suggest their potential value as additional tools in disease diagnosis.

Validation of the St. George's Respiratory Questionnaire in Nepal.

The St. George's Respiratory Questionnaire (SGRQ) is a standardized questionnaire for measuring impaired health and perceived well-being in chronic airway disease, but it is not available in the Nepali language. We translated the original SGRQ into Nepali and validated its use in 150 individuals aged 40 to 80 years with and without COPD.We also examined if the SGRQ could be used as a screening tool to identify individuals at risk for COPD. We translated the SGRQ following a standard protocol. The validation study was then conducted in both community and hospital-based settings in Nepal. We enrolled 100 participants from a community setting who were not actively seeking medical care, 50 of which met criteria for chronic obstructive pulmonary disease (COPD) (post-bronchodilator forced expiratory volume in 1 second [FEV1]/ forced vital capacity [FVC]<70%) and 50 who did not. We also enrolled 50 participants with an established diagnosis of COPD who attended outpatient pulmonary clinics. All participants completed the questionnaire. We used linear regressions to compare average SGRQ scores by disease status categories and by lung function values, adjusted for age, sex, height and body mass index (BMI).All 150 participants (mean age 59.8 years, 48% male, mean BMI 20.5 kg/m2) completed the SGRQ. In multivariable regression, the average SGRQ total score was 23.9 points higher in established cases of COPD and 18.1 points higher in community cases of COPD when compared to participants without COPD living in the community (all p<0.001). The SGRQ total score also increased by an average of 2.1 points for each 100 mL decrease in post-FEV1 (p<0.001). The area-under-the-curve for the SGRQ total score as a predictor of COPD was 0.77 (95% confidence interval [CI] 0.68 to 0.85) and the optimal cutoff to identify COPD was 33 points.We developed a Nepali-validated version of SGRQ, which correlated well with both disease status and severity.

Chronic obstructive pulmonary disease and inflammatory biomarkers in retired workers exposed to inorganic dusts

The persistent lung inflammation results in inhaled toxic dusts bring pathologic changes in airway system that lead to development of chronic obstructive pulmonary disease (COPD). Recently, beyond local inflammation in lung, COPD is regarded as chronic systemic inflammatory disease linked to extra pulmonary disease. Therefore, several local and systemic inflammatory biomarkers were needed to be investigated for understanding of COPD. Hence, this current study was aimed to identify the association between COPD and inflammatory biomarkers in workers exposed to inorganic dusts. Clara cell secretary proteins (CC-16) and surfactant protein D (SP-D) were chosen as local inflammatory biomarker, high sensitive Creactive protein (hsCRP), interleukin (IL)-6, serum amyloid protein A (SAA) and tyrosine lysine leucine 40 (YKL-40) were chosen as systemic inflammatory markers in 39 COPD and 39 control group. In current study, CC-16, hsCRP and YKL-40 were linked to COPD in conditional logistic regression model. Furthermore, CC-16 and hsCRP are related to COPD independently to working duration and smoking history. These results suggest that local and inflammatory biomarker could be independent predictor of COPD in worker exposed to inorganic dusts.

Potential misclassification of causes of death from COPD

Little is known about causes of death in chronic obstructive pulmonary disease (COPD) and the validity of mortality statistics in COPD. The present authors examined causes of death using data from the Copenhagen City Heart Study. Of the 12,979 subjects with sufficient data from the baseline examination during 1976-1978, 6,709 died before 2001. Of these, 242 died with COPD as cause of death. Among subjects with at least severe COPD at baseline, only 24.9% had COPD as cause of death and, in almost half of the cases where COPD was listed as cause of death, the subject had a normal forced expiratory volume in one second /forced vital capacity ratio at baseline. In COPD patients, having COPD on the death certificate was associated with chronic mucus hypersecretion (CMH) at baseline, an odds ratio (OR) of 3.6 (95% confidence interval 1.7-7.7), and being female (OR 2.7 (1.3-5.6)). In subjects without COPD, CMH and smoking were predictors of COPD as underlying cause of death, ORs 2.3 (1.5-3.7) and 2.2 (1.4-3.6), respectively. It was concluded that chronic obstructive pulmonary disease is underreported on death certificates, that biases in the use of chronic obstructive pulmonary disease as cause of death can be assessed, and that possible "over-diagnosis" of chronic obstructive pulmonary disease on death certificates in subjects unlikely to have significant disease should initiate caution when using causes of mortality in chronic obstructive pulmonary disease epidemiology.

Airway inflammation in COPD: physiological outcome measures and induced sputum.

Chronic obstructive pulmonary disease (COPD) is a result of airway inflammation, and the best predictor of COPD is the early detection of airflow limitation by spirometry. The Global Initiative for Obstructive Lung Disease Workshop Report defines airflow limitation using simple spirometric indices. Available guidelines categorise the severity of COPD using forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), with symptoms playing a minor role in the assessment. Current standards define COPD by progressive loss of FEV1, and thus longitudinal decline in FEV1 will be the primary outcome variable for intervention studies aimed at preventing or reducing the loss of pulmonary function. There is evidence, however, that the variable FEV1/FVC and FEV1 are often not measured properly in all settings. This article will discuss the roles of physiological measurements in diagnosing COPD and physiological outcome measures for COPD. It does not formally compare physiological measures with other outcome measures, such as symptoms or quality of life. Additionally, improved treatment of established disease requires a better understanding of the inflammatory process and its clinical effects and treatment. The inflammatory process, and how drugs affect it, can be studied noninvasively or relatively noninvasively by using refined methods of examining spontaneous or induced sputum. Enhanced understanding of the use of induced sputum will assist in predicting patients' responses to short- and long-term inhaled corticosteroid treatment, and the methods of sputum examination need to be simplified so that they can be applied more easily to clinical practice.

Risk of chronic obstructive pulmonary disease. Collaborative assessment of the validity of the Tecumseh index of risk.

Predictors of chronic obstructive pulmonary disease (COPD) have been identified in the prospective epidemiologic study of the population of Tecumseh, Michigan. Risk of developing COPD within 10 yr can be estimated from a profile that includes as risk factors age, sex, cigarette smoking habits, and forced expiratory volume in one second (FEV1). The index of risk placed 63% of male incidence cases and 64% of female incidence cases in the top 10% of the risk distribution and 81% of male and 86% of female COPD cases in the top 20% of the risk distribution for Tecumseh. The validity of the Tecumseh index of risk for other populations was determined in a collaborative investigation of data collected in longitudinal epidemiologic studies in Baltimore, Boston, Framingham, Louisiana, Staveley, and Tucson. The extent to which the risk model fitted these data sets was assessed by comparing predicted (or expected) onsets of COPD in each population with observations made in each study. The predictors of COPD identified in Tecumseh were shown to be the most important risk factors in the other populations as well. The goodness-of-fit of the index was satisfactory overall. In all populations, a high risk score was associated with an increased incidence of COPD, thus confirming the predictive ability of the risk index. The Tecumseh index of risk provides a practical method for developing a risk profile from answers to standard questions and simple tests of lung function. Risks are greatest for heavy cigarette smokers with reduced lung function, lower in smokers who stop smoking or reduce their cigarette consumption, and lowest of all in nonsmokers with above average lung function.(ABSTRACT TRUNCATED AT 250 WORDS)