Early detection of COPD by high risk population spirometric screening

COPD is the most frequent chronic lung disease in Poland. The disease is however under-diagnosed, especially at the early stages. The aim of the study was to assess the efficacy of spirometric screening for COPD in middle aged smokers. Informations on causes and symptoms of COPD were disseminated in mass media in 14 large cities. Subject aged over 39 and with smoking history of > 10 packyears were invited for a free spirometry in local chest clinic. However, everyone attending had the spirometry performed. Spirometry was performed according to ATS recommendations. Airway obstruction (AO) was diagnosed when FEV1/FVC < 85% of N and categorised as mild (FEV1 > 70% of N), moderate (FEV1 50-69% of N) or severe (FEV1 < 50% of N). Spirometry was accompanied by an antismoking advice. RESULTS: 12.781 subjects were screened (mean age 52 +/- 12 years, 57% males). In 8.269 subjects who complied with inclusion criteria AO was diagnosed in 29.8% (mild in 10.9%, moderate in 12% and severe in 6.9%). In smokers < 40 years of age and a history of < 10 packyears AO was found in 8.8% (mild in 6.0%, moderate in 1.8% and severe in 1.0%). CONCLUSION: Mass spirometry is an effective and easy method for early detection of COPD.     

The rate of airflow limitation among the elderly undergoing spirometry in a university hospital

The aim of this study was to examine the rate of airflow limitation among the elderly undergoing spirometry prior to surgical operation, and to evaluate whether or not spirometry is useful for the early detection of COPD. A total of 3,086 patients (1,717 men and 1,369 women) ranging in age from 40 to 93 underwent screening spirometry from January to December 2003 in Tokyo Medical and Dental University Hospital. Among the total population, 2,135 patients (1,188 men and 947 women) were ordered to undergo the spirometry prior to surgical operation, airflow limitation (FEV1/FVC < 70%) was observed in 19.5% (n=417) of the cases and was considerably more frequent in men than in women(27.0%[n=321] vs. 10.1%[n=96]). The rate of FEV1/FVC < 70% in those 2,135 patients increased with age: 6.2%, 9.9%, 19.2%, 32.5% and 34.1% of patients in their 40s, 50s, 60s, 70s, 80s and over, respectively. Among the patients with airflow limitation, 35% of the cases revealed FEV1 > or = 80% predicted; 50%, 50 < or = FEV1 < 80% predicted; 14%, 30 < or = FEV1 < 50% predicted; 1%, FEV1 < 30% predicted. Patients with mild to moderate airflow limitation rarely consulted the pulmonary medicine department. The prevalence of airflow limitation was more frequent among in- and out-patients than in the random sample population. Spirometry prior to surgical operation is useful for the early detection of COPD and these data could be an important source for medical staff seeking a definitive diagnosis of patients revealing airflow limitation.     

Comparison of the Prevalence of Chronic Obstructive Pulmonary Disease Diagnosed by Lower Limit of Normal and Fixed Ratio Criteria

The Global Initiative of Chronic Obstructive Lung Disease (GOLD) guidelines define chronic obstructive pulmonary disease (COPD) in subjects with FEV₁/FVC <0.7. However, the use of this fixed ratio may result in over-diagnosis of COPD in the elderly, especially with mild degree of COPD. The lower limit of normal (LLN) can be used to minimize the potential misclassification. The aim of this study was to evaluate the impact of different definitions of airflow obstruction (LLN or fixed ratio of FEV₁/FVC) on the estimated prevalence of COPD in a population-based sample. We compared the prevalence of COPD and its difference diagnosed by different methods using either fixed ratio (FEV₁/FVC <0.7) or LLN criterion (FEV₁/FVC below LLN). Among the 4,816 subjects who had performed spirometry, 2,728 subjects met new ATS/ERS spirometry criteria for acceptability and repeatability. The prevalence of COPD was 10.9% (14.7% in men, 7.2% in women) by LLN criterion and 15.5% (21.8% in men, 9.1% in women) by fixed ratio of FEV₁/FVC among subjects older than 45 yr. The difference of prevalence between LLN and fixed ratio of FEV₁/FVC was even higher among subjects with age ≥65, 14.9% and 31.1%, respectively. In conclusion, the prevalence of COPD by LLN criterion was significantly lower in elderly compared to fixed ratio of FEV₁/FVC. Implementing LLN criterion instead of fixed ratio of FEV₁/FVC may reduce the risk of over-diagnosis of COPD in elderly people.     

Quality of life in smokers: focus on functional limitations rather than on lung function?

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of severity of chronic obstructive pulmonary disease (COPD) is based solely on obstruction and does not capture physical functioning. The hypothesis that the Medical Research Council (MRC) dyspnoea scale would correlate better with quality of life than the level of airflow limitation was examined. AIM: To study the associations between quality of life in smokers and limitations in physical functioning (MRC dyspnoea scale) and, quality of life and airflow limitation (GOLD COPD stages). DESIGN: Cross-sectional study. SETTING: The city of IJsselstein, a small town in the centre of The Netherlands. METHOD: Male smokers aged 40-65 years without a prior diagnosis of COPD and enlisted with a general practice, participated in this study. Quality of life was assessed by means of a generic (SF-36) and a disease-specific, questionnaire (QOLRIQ). RESULTS: A total of 395 subjects (mean age 55.4 years, pack years 27.1) performed adequate spirometry and completed the questionnaires. Limitations of physical functioning according to the MRC dyspnoea scale were found in 25.1% (99/395) of the participants and airflow limitation in 40.2% (159/395). The correlations of limitations of physical functioning with all quality-of-life components were stronger than the correlations of all quality-of-life subscales with the severity of airflow limitation. CONCLUSION: In middle-aged smokers the correlation of limitations of physical functioning (MRC dyspnoea scale) with quality of life was stronger than the correlation of the severity of airflow limitation with quality of life. Future staging systems of severity of COPD should capture this and not rely on forced expiratory volume in one second (FEV1) alone.     

Prevalence of chronic obstructive pulmonary disease in blacks.

Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality in blacks. The prevalence of COPD among blacks was estimated from the spirometry data obtained from the first National Health and Nutrition Examination Survey (NHANES), 1971-1975. Of 873 subjects, 585 (67%) had acceptable spirometry trials. Chronic obstructive pulmonary disease was defined as a forced expiratory volume in one second (FEV1) less than 65% of the predicted value. The mean FEV1 percentage predicted was 96.7%. The overall prevalence of COPD was 5.4%; 3.7% for males and 6.7% for females. The prevalence was significantly higher with age for both males and females. The multiple logistic regression analyses showed that age and sex were associated with COPD but respiratory symptoms did not attain statistical significance.     

Genome-wide linkage analysis of severe, early-onset chronic obstructive pulmonary disease: airflow obstruction and chronic bronchitis phenotypes

Familial aggregation of chronic obstructive pulmonary disease (COPD) has been demonstrated, but linkage analysis of COPD-related phenotypes has not been reported previously. An autosomal 10 cM genome-wide scan of short tandem repeat (STR) polymorphic markers was analyzed for linkage to COPD-related phenotypes in 585 members of 72 pedigrees ascertained through severe, early-onset COPD probands without severe alpha1-antitrypsin deficiency. Multipoint non-parametric linkage analysis (using the ALLEGRO program) was performed for qualitative phenotypes including moderate airflow obstruction [forced expiratory volume at one second (FEV(1)) < 60% predicted, FEV(1)/FVC < 90% predicted], mild airflow obstruction (FEV(1) < 80% predicted, FEV(1)/FVC < 90% predicted) and chronic bronchitis. The strongest evidence for linkage in all subjects was observed at chromosomes 12 (LOD = 1.70) and 19 (LOD = 1.54) for moderate airflow obstruction, chromosomes 8 (LOD = 1.36) and 19 (LOD = 1.09) for mild airflow obstruction and chromosomes 19 (LOD = 1.21) and 22 (LOD = 1.37) for chronic bronchitis. Restricting analysis to cigarette smokers only provided increased evidence for linkage of mild airflow obstruction and chronic bronchitis to several genomic regions; for mild airflow obstruction in smokers only, the maximum LOD was 1.64 at chromosome 19, whereas for chronic bronchitis in smokers only, the maximum LOD was 2.08 at chromosome 22. On chromosome 12p, 12 additional STR markers were genotyped, which provided additional support for an airflow obstruction locus in that region with a non-parametric multipoint approach for moderate airflow obstruction (LOD = 2.13) and mild airflow obstruction (LOD = 1.43). Using a dominant model with the STR markers on 12p, two point parametric linkage analysis of all subjects demonstrated a maximum LOD score of 2.09 for moderate airflow obstruction and 2.61 for mild airflow obstruction. In smokers only, the maximum two point LOD score for mild airflow obstruction was 3.14. These observations provide suggestive evidence that there is a locus on chromosome 12p which contributes to susceptibility to early-onset COPD.     

COPD 患者Th17 细胞和Treg 细胞介导的免疫应答变化及免疫失衡与肺功能的关系研究

目的:探讨慢性阻塞性肺疾病(COPD)患者外周血Th17 细胞和调节性T 细胞(Treg)及其介导的免疫应答变化与患者肺功能的关系。方法:选取本院呼吸内科收治的90 例COPD 患者(COPD 组)和同期年龄、性别基本匹配的45 例健康体检对象作为对照组,并根据COPD 病情进行亚组分析,分别测定各组研究对象肺功能指标、Th17 细胞、Treg 细胞及血清炎症因子水平。结果:在COPD 患者间,随着病情加重,FEV1%、FVC%、FEV1/ FVC 比值中度COPD 组<重度COPD 组<极重度组(P<0.05);在COPD 患者间,随着病情加重,外周血中Th17 细胞、Th17/ Treg 比值中度COPD 组<重度COPD 组<极重度组(P<0.05),外周血Treg 细胞比值中度COPD 组>重度COPD 组>极重度组(P<0.05),且外周血Th17 细胞、Treg 细胞相关细胞因子变化具有一致性;COPD 患者的肺功能指标FEV1%、FVC%、FEV1/ FVC 与外周血中Th17 细胞、Th17/ Treg 比值呈显著的负相关关系(P<0.05),肺功能指标FEV1%、FVC%、FEV1/ FVC 与外周血Treg 比值呈显著的正相关关系(P<0.05)。结论:COPD外周血Th17/ Treg 比值与患者肺功能下降具有显著的相关性。     

Hsa-Mir-320c,Hsa-Mir-200c-3p,and Hsa-Mir-449c-5p as Potential Specific miRNA Biomarkers of COPD: A Pilot Study

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease commonly induced by cigarette smoke. The expression of miRNAs can be altered in patients with COPD and could be used as a biomarker. We aimed to identify a panel of miRNAs in bronchoalveolar lavage (BAL) to differentiate COPD patients from smokers and non-smokers with normal lung function. Accordingly, forty-five subjects classified as COPD, smokers, and non-smokers (n = 15 per group) underwent clinical, functional characterization and bronchoscopy with BAL. The mean age of the studied population was 61.61 ± 12.95 years, BMI 25.72 ± 3.82 Kg/m², FEV1/FVC 68.37 ± 12.00%, and FEV1 80.07 ± 23.63% predicted. According to microarray analysis, three miRNAs of the most upregulated were chosen: miR-320c, miR-200c-3p, and miR-449c-5p. These miRNAs were validated by qPCR and were shown to be differently expressed in COPD patients. ROC analysis showed that these three miRNAs together had an area under the curve of 0.89 in differentiating COPD from controls. Moreover, in silico analysis of candidate miRNAs by DIANA-miRPath showed potential involvement in the EGFR and Hippo pathways. These results suggest a specific 3-miRNA signature that could be potentially used as a biomarker to distinguish COPD patients from smokers and non-smoker subjects.     

GOLD guideline and recommendation for role of spirometry in COPD

COPD is currently the fourth leading cause of death in the world, and further increase in its prevalence and mortality have been predicted for the coming decades. To decrease the morbidity and mortality due to COPD, better recognition of the risk of COPD and improvement in prevention and management of COPD is required. Many national and international societies of respiratory diseases have developed guidelines for COPD. In the GOLD report, COPD is a disease status characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. Airflow limitation in COPD is best measured through spirometry, which is a key to the diagnosis and management of the disease. It is the most standardized, reproducible, and objective measurement of airflow limitation available. A decrease in the ratio of FEV1 to FVC is often the first sign of developing airflow limitation. In Japan, a major problem is the lack of guidelines for standardization of spirometry. To achieve consistently accurate test results, not only standardization of spirometry but also propagation of proper procedure and evaluation of spirometry are required.     

Putative roles of circulating resistin in patients with asthma, COPD and cigarette smokers

Aims: To investigate the hypothesis that circulating resistin reflects the degree of pulmonary inflammation, this study explores putative roles of resistin in patients with acute and stable inflammatory obstructive airway diseases and cigarette smokers. Methods: We determined complements C3, C4, fasting resistin, insulin, glucose and lipid profile; calculated insulin resistance (homeostasis model assessment (HOMA-IR) in patients with acute asthma exacerbation (n = 34); stable asthma (n = 26) and stable chronic obstructive pulmonary disease (COPD; n = 26), cigarette smokers (n = 81), and healthy control subjects (n = 42). We determined the associations between these variables and pulmonary function tests.Results: Patients with COPD, acute and stable asthma had significantly higher resistin and insulin than control subjects. Resistin, insulin, HOMA-IR, FEV1% and FEV1/FVC were significantly (p < 0.05) different between patients with acute asthma compared with stable asthma and COPD; smokers had similar levels of resistin, C3 and C4 as patients with asthma and COPD. In smokers, patientswith asthma or COPD, resistin showed significant inverse correlations with FEV1%; FEV1/FVC% and positive significant correlations with BMI and HOMA-IR. Logistic regression showed that resistin is associated (p < 0.05) with inflammatory obstructive airways disease − odds ratio (OR) = 1.22 and smoking OR = 1.18.Conclusion: Resistin may be a disease activity marker and may contribute to insulin resistance in smokers, asthma and COPD.     

Awareness of airflow obstruction together with antismoking advice increases success in cessation smoking

COPD is one of the leading causes of mortality and increased morbidity in developed world. In advanced disease it also imposes an important economic burden on societies. The main etiologic factor for COPD is tobacco smoking. The aim of the study was to asses if the awareness of airflow obstruction combined together with a minimal antismoking advice in middle aged smokers increases the quitting rate. Out of smokers participating in mass spirometric screening for COPD in five polish towns, we invited 734 (300 with airflow limitation and 247 with normal lung function) for a follow-up. During the second visit, at one year, spirometry was performed and smoking status was assessed. Non-smoking was validated with carbon monoxide measurements in exhaled breath. Patients who did not come for the follow-up visit were considered as smokers. Of 734 smokers invited, 543 (74%) presented for the follow-up visit. All smokers tried to modify the habit. Number of cigarettes smoked at one year was reduced by -5.5 (p < 0.001) in patients with airflow limitation and -2.2 (ns) in smokers with normal lung function. One year quit rate in smokers with airflow limitation was 11.1% vs 7.6% in smokers with normal lung function (ns). When the calculation was made for those who had the follow-up the quit rates were 15.1% vs 9.9% (p < 0.05). Cessation of smoking was correlated with lung function. Those smokers who stopped smoking permanently or tried to quit had lower FEV1 (p < 0.01) and FEV1/FVC (p < 0.05), than those who continued to smoke.     

Predictors of pulmonary function response to treatment with salmeterol/fluticasone in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and responses to therapies are highly variable. The aim of this study was to identify the predictors of pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD. A total of 127 patients with stable COPD from the Korean Obstructive Lung Disease (KOLD) Cohort, which were prospectively recruited from June 2005 to September 2009, were analyzed retrospectively. The prediction models for the FEV(1), FVC and IC/TLC changes after 3 months of treatment with salmeterol/fluticasone were constructed by using multiple, stepwise, linear regression analysis. The prediction model for the FEV(1) change after 3 months of treatment included wheezing history, pre-bronchodilator FEV(1), post-bronchodilator FEV(1) change and emphysema extent on CT (R = 0.578). The prediction models for the FVC change after 3 months of treatment included pre-bronchodilator FVC, post-bronchodilator FVC change (R = 0.533), and those of IC/ TLC change after 3 months of treatment did pre-bronchodilator IC/TLC and post-bronchodilator FEV(1) change (R = 0.401). Wheezing history, pre-bronchodilator pulmonary function, bronchodilator responsiveness, and emphysema extent may be used for predicting the pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD.     

SP-D polymorphisms and the risk of COPD

Introduction: There are limited data linking serum levels of surfactant protein D, its genetic polymorphisms to the risk of Chronic Obstructive Pulmonary Disease (COPD). Objectives: We sought to investigate these relationships using a case control study design. Methods: Post bronchodilator values of FEV1/FVC < 0.7 were used to diagnose COPD patients (n=115). Controls were healthy subjects with normal spirometry (n=106) Single nucleotide polymorphisms (rs721917, rs2243639, rs3088308) were genotyped using polymerase chain reaction (PCR) and restriction analysis. Serum SP-D levels were measured using a specific immunoassay. Results: Allele 'A' at rs3088308 (p < 0.00, B= -0.41) and 'C' allele at rs721917 (p=0.03; B= -0.30) were associated with reduced serum SP-D levels. Genotype 'T/T' at rs721917 was significantly associated with risk of COPD (p=0.01). Patients with repeat exacerbations had significantly higher serum SP-D even after adjusting for genetic factors. Conclusions: We report for the first time that rs3088308 is an important factor influencing systemic SP-D levels and confirm the previous association of rs721917 to the risk of COPD and serum SP-D levels.     

Influence of orthopnoea position on spirometric and plethysmographic parameters in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterized by the lack or only slight reversibility of obstruction which can be assessed by spirometry after inhalation of short-acting beta 2-mimetic (e.g. Salbutamol). The aim of the study was to determine if subjective decrease in dyspnoea sensation notified by COPD patients in orthopnoea position is reflected in spirometry and plethysmography. The study was carried out in the group of 30 patients with COPD (FEV1 = 30-70% of predicted value) as well as in 30 sex- and age-matched non-smoking healthy subjects. We observed the increase of spirometric parameters (FEV1, FEV1%VC, FEF75, PEF) and the decrease of plethysmographic parameters (RTOT, RV, RV%TLC) after the change from the initial to orthopnoea position (p < 0.001). The obtained results show that orthopnoea position leads to the decline of obstruction degree, pulmonary hyperinflation and the decrease of dyspnoea sensation.     

Comorbidities of chronic obstructive pulmonary disease in koreans: a population-based study

Chronic obstructive pulmonary disease (COPD) includes pulmonary components with increased comorbidity rates, as well as being a systemic disease. Comorbidities may frequently occur in COPD patients over 40 yr old. We report the comorbidities of patients with COPD, diagnosed by spirometry, in a population-based epidemiologic survey in Korea. Data were derived from the fourth Korean Health and Nutrition Examination Survey in 2008, a stratified multistage clustered probability design survey of a sample representing the entire population of Korea. Results of spirometry and various health-related questionnaires were analyzed in 2,177 subjects aged ≥ 40 yr. The prevalence of COPD (FEV(1)/FVC < 0.7) in subjects ≥ 40 yr of age was 14.1%. Multivariate analysis showed that underweight (odds ratio [OR] 3.07, 95% confidence interval [CI] 1.05-8.98), coronary heart disease (OR, 0.43; 95% CI, 0.20-0.93) and dyslipidemia (OR, 0.61; 95% CI, 0.45-0.82) were significantly associated with COPD, whereas allergic rhinitis, anemia, arthritis, chronic renal failure, depression, diabetes mellitus, hypertension, gastrointestinal ulcer, and osteoporosis were not. Underweight might be more prevalent but coronary heart disease and dyslipidemia are less prevalent in Koreans with than without COPD in population setting.     

Genome-wide linkage analysis of bronchodilator responsiveness and post-bronchodilator spirometric phenotypes in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a common, complex disease associated with significant and increasing morbidity and mortality. The cardinal feature of COPD is persistent airflow obstruction, measured by reductions in quantitative spirometric indices including forced expiratory volume at one second (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FEV(1)/FVC). However, many patients have substantial improvement in spirometric measures with inhaled bronchodilator medications, and bronchodilator responsiveness (BDR) has been associated with disease severity and progression. To identify susceptibility loci for BDR phenotypes, we performed a 9 cM genome scan in 72 pedigrees (n=560 members) ascertained through probands with severe, early-onset COPD. Multipoint variance component linkage analysis was performed for quantitative phenotypes including BDR measures and post-bronchodilator FEV(1) and FEV(1)/FVC. Post-bronchodilator FEV(1) was linked to multiple regions, most significantly to markers on chromosome 8p (LOD=3.30) and 1q (LOD=2.24). Post-bronchodilator FEV(1)/FVC was also linked to multiple regions, most significantly to markers on chromosome 2q (LOD=4.42) and 1q (LOD=2.52). When compared with pre-bronchodilator spirometric indices, the post-bronchodilator values demonstrated increased evidence of linkage in multiple genomic regions. In particular, the LOD score for the 8p linkage to FEV(1) roughly doubled from 1.58 to 3.30. Candidate regions on chromosomes 4p (LOD=1.28), 4q (LOD=1.56), and 3q (LOD=1.50) gave the strongest evidence for linkage to BDR measures. Our results provide evidence for significant linkage to airflow obstruction susceptibility loci on chromosomes 2q and 8p, and further suggest that post-bronchodilator spirometric measures are optimal phenotypes for COPD genetic studies. This study has also identified several genomic regions that could contain loci regulating BDR in early-onset COPD families.     

COPD education and cognitive behavioral therapy group treatment for clinically significant symptoms of depression and anxiety in COPD patients: a randomized controlled trial

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects 14 to 20 million Americans and is associated with increased prevalence of affective disorders, contributing significantly to disability. This study compared cognitive behavioral therapy (CBT) group treatment for anxiety and depression with COPD education for COPD patients with moderate-to-severe anxiety and/or depressive symptoms. METHOD: A randomized controlled trial (RCT) was conducted between 11 July 2002 and 30 April 2005 at the Michael E. DeBakey VA Medical Center, Houston, TX. Participants were 238 patients treated for COPD the year before, with forced expiratory value in 1 second (FEV)1/forced vital capacity (FVC)<70% and FEV1<70% predicted, and symptoms of moderate anxiety and/or moderate depression, who were being treated by a primary care provider or pulmonologist. Participants attended eight sessions of CBT or COPD education. Assessments were at baseline, at 4 and 8 weeks, and 4, 8 and 12 months. Primary outcomes were disease-specific and generic quality of life (QoL) [Chronic Respiratory Questionnaire (CRQ) and Medical Outcomes Survey Short Form-36 (SF-36) respectively]. Secondary outcomes were anxiety [Beck Anxiety Inventory (BAI)], depressive symptoms [Beck Depression Inventory-II (BDI-II)], 6-minute walk distance (6MWD) and use of health services. RESULTS: Both treatments significantly improved QoL, anxiety and depression (p<0.005) over 8 weeks; the rate of change did not differ between groups. Improvements were maintained with no significant change during follow-up. Ratios of post- to pretreatment use of health services were equal to 1 for both groups. CONCLUSIONS: CBT group treatment and COPD education can achieve sustainable improvements in QoL for COPD patients experiencing moderate-to-severe symptoms of depression or anxiety.