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1.  N-acetylcysteine instead of theophylline in patients with COPD who are candidates for elective off-pump CABG surgery: Is it possible in cardiovascular surgery unit? 
Saudi Journal of Anaesthesia  2013;7(2):151-154.
Forced expiratory volume in one second (FEV1) is a good predictor of chronic obstructive pulmonary disease (COPD). COPD is characterized by a chronic limitation of airflow. This study was designed to compare the effects and complications of theophylline alone, N-acetylcysteine (NAC) alone, and a combination of the two drugs on the rates of FEV1 in patients with COPD who were candidates for off-pump coronary artery bypass graft (CABG) surgery.
This clinical trial was performed on 100 patients who had a smoking history of 27 pack years with a range of 20 to 40 pack years but were not heavy smokers and were candidates for elective off-pump CABG surgery in Afshar Cardiovascular Hospital, Yazd, Iran. The patients with a history of asthma and bronchospasm and non-COPD respiratory disorders were excluded. There were three groups, that is, the theophylline group (n=33) that received theophylline 10 mg/kg TDS after consumption of food, NAC group (n=33) who received NAC 10-15 mg/kg BD after consumption of food, and the combined group (n=32) who received theophylline and NAC together. Data were analyzed by analysis of variance (ANOVA), Chi-square, and exact test for quantitative and qualitative variables.
One hundred patients with COPD enrolled in this study as possible candidates for CABG surgery. Average age of the patients was 60.36±10.21 years. Of the participants, 83 (83.3%) were male and 17 (17%) were female. Rate of postoperative FEV1 to basal FEV1 was 0.76±0.32, 0.66±0.22, and 0.69±0.24 in the treatments with theophylline, NAC, and the combination, respectively. Theophylline, NAC, and a combination of these drugs can decrease the rate of postoperative FEV1 compared to basal FEV1 significantly. (P=0.0001)
Theophylline alone, NAC alone, and a combination of these drugs improve pulmonary function, and there are no significant differences between these protocols. Stomach discomfort and cardiac complications in treatment with theophylline alone is significantly higher than NAC alone and the combination.
PMCID: PMC3737690  PMID: 23956714
Chronic obstructive pulmonary disease; elective off-pump coronary artery bypass graft; N-acetylcysteine; theophylline
2.  Chronic obstructive pulmonary disease in the older adult: what defines abnormal lung function? 
Thorax  2006;62(3):237-241.
The Global Initiative on Obstructive Lung Disease stages for chronic obstructive pulmonary disease (COPD) uses a fixed ratio of the post‐bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of 0.70 as a threshold. Since the FEV1/FVC ratio declines with age, using the fixed ratio to define COPD may “overdiagnose” COPD in older populations.
To determine morbidity and mortality among older adults whose FEV1/FVC is less than 0.70 but more than the lower limit of normal (LLN).
The severity of COPD was classified in 4965 participants aged ⩾65 years in the Cardiovascular Health Study using these two methods and the age‐adjusted proportion of the population who had died or had a COPD‐related hospitalisation in up to 11 years of follow‐up was determined.
1621 (32.6%) subjects died and 935 (18.8%) had at least one COPD‐related hospitalisation during the follow‐up period. Subjects (n = 1134) whose FEV1/FVC fell between the LLN and the fixed ratio had an increased adjusted risk of death (hazard ratio (HR) 1.3, 95% CI 1.1 to 1.5) and COPD‐related hospitalisation (HR 2.6, 95% CI 2.0 to 3.3) during follow‐up compared with asymptomatic individuals with normal lung function.
In this cohort, subjects classified as “normal” using the LLN but abnormal using the fixed ratio were more likely to die and to have a COPD‐related hospitalisation during follow‐up. This suggests that a fixed FEV1/FVC ratio of <0.70 may identify at‐risk patients, even among older adults.
PMCID: PMC2117148  PMID: 17090573
3.  Incidence and determinants of moderate COPD (GOLD II) in male smokers aged 40–65 years: 5-year follow up 
Chronic obstructive pulmonary disease (COPD) is a major health problem with an estimated prevalence of 10–15% among smokers. The incidence of moderate COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), is largely unknown.
To determine the cumulative incidence of moderate COPD (forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC] <0.7 and FEV1 <80% predicted) and its association with patient characteristics in a cohort of male smokers.
Prospective cohort study.
The city of IJsselstein, a small town in the Netherlands.
Smokers aged 40–65 years who were registered with local GPs, participated in a study to identify undetected COPD. Baseline measurements were taken in 1998 of 399 smokers with normal spirometry (n = 292) or mild COPD (FEV1/FVC <0.7 and FEV1 ≥80% predicted, n = 107) and follow-up measurements were conducted in 2003.
After a mean follow-up of 5.2 years, 33 participants developed moderate COPD (GOLD II). This showed an estimated cumulative incidence of 8.3% (95% CI = 5.8 to 11.4) and a mean annual incidence of 1.6%. No participant developed severe airflow obstruction. The risk of developing moderate COPD in smokers with baseline mild COPD (GOLD I) was five times higher than in those with baseline normal spirometry (one in five versus one in 25).
In a cohort of middle-aged male smokers, the estimated cumulative incidence of moderate COPD (GOLD II) over 5 years was relatively high (8.3%). Age, childhood smoking, cough, and one or more GP contacts for lower respiratory tract problems were independently associated with incident moderate COPD.
PMCID: PMC1876630  PMID: 16953996
incidence; middle-age; moderate COPD; patient characteristics; smokers
4.  Comparison of spirometry criteria for the diagnosis of COPD: results from the BOLD study 
The European respiratory journal  2009;34(3):588-597.
Published guidelines recommend spirometry to accurately diagnose chronic obstructive pulmonary disease (COPD). However, even spirometry-based COPD prevalence estimates can vary widely. We compared properties of several spirometry-based COPD definitions using data from the international Burden of Obstructive Lung Disease (BOLD)study.
14 sites recruited population-based samples of adults aged ≥40 yrs. Procedures included standardised questionnaires and post-bronchodilator spirometry. 10,001 individuals provided usable data.
Use of the lower limit of normal (LLN) forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio reduced the age-related increases in COPD prevalence that are seen among healthy never-smokers when using the fixed ratio criterion (FEV1/FVC <0.7) recommended by the Global Initiative for Chronic Obstructive Lung Disease. The added requirement of an FEV1 either <80% predicted or below the LLN further reduced age-related increases and also led to the least site-to-site variability in prevalence estimates after adjusting for potential confounders. Use of the FEV1/FEV6 ratio in place of the FEV1/FVC yielded similar prevalence estimates.
Use of the FEV1/FVC
PMCID: PMC3334278  PMID: 19460786
Adult; chronic obstructive pulmonary disease; epidemiology
Wilk, Jemma B. | Shrine, Nick R. G. | Loehr, Laura R. | Zhao, Jing Hua | Manichaikul, Ani | Lopez, Lorna M. | Smith, Albert Vernon | Heckbert, Susan R. | Smolonska, Joanna | Tang, Wenbo | Loth, Daan W. | Curjuric, Ivan | Hui, Jennie | Cho, Michael H. | Latourelle, Jeanne C. | Henry, Amanda P. | Aldrich, Melinda | Bakke, Per | Beaty, Terri H. | Bentley, Amy R. | Borecki, Ingrid B. | Brusselle, Guy G. | Burkart, Kristin M. | Chen, Ting-hsu | Couper, David | Crapo, James D. | Davies, Gail | Dupuis, Josée | Franceschini, Nora | Gulsvik, Amund | Hancock, Dana B. | Harris, Tamara B. | Hofman, Albert | Imboden, Medea | James, Alan L. | Khaw, Kay-Tee | Lahousse, Lies | Launer, Lenore J. | Litonjua, Augusto | Liu, Yongmei | Lohman, Kurt K. | Lomas, David A. | Lumley, Thomas | Marciante, Kristin D. | McArdle, Wendy L. | Meibohm, Bernd | Morrison, Alanna C. | Musk, Arthur W. | Myers, Richard H. | North, Kari E. | Postma, Dirkje S. | Psaty, Bruce M. | Rich, Stephen S. | Rivadeneira, Fernando | Rochat, Thierry | Rotter, Jerome I. | Artigas, María Soler | Starr, John M. | Uitterlinden, André G. | Wareham, Nicholas J. | Wijmenga, Cisca | Zanen, Pieter | Province, Michael A. | Silverman, Edwin K. | Deary, Ian J. | Palmer, Lyle J. | Cassano, Patricia A. | Gudnason, Vilmundur | Barr, R. Graham | Loos, Ruth J. F. | Strachan, David P. | London, Stephanie J. | Boezen, H. Marike | Probst-Hensch, Nicole | Gharib, Sina A. | Hall, Ian P. | O’Connor, George T. | Tobin, Martin D. | Stricker, Bruno H.
Rationale: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known.
Objectives: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases.
Methods: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV1 and its ratio to FVC (FEV1/FVC) both less than their respective lower limits of normal as determined by published reference equations.
Measurements and Main Results: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers. Gene expression studies confirmed the presence of CHRNA5/3 in lung, airway smooth muscle, and bronchial epithelial cells. A single-nucleotide polymorphism in HTR4, a gene previously related to FEV1/FVC, achieved genome-wide statistical significance in combined meta-analysis. Top single-nucleotide polymorphisms in ADAM19, RARB, PPAP2B, and ADAMTS19 were nominally replicated in the COPD meta-analysis.
Conclusions: These results suggest an important role for the CHRNA5/3 region as a genetic risk factor for airflow obstruction that may be independent of smoking and implicate the HTR4 gene in the etiology of airflow obstruction.
PMCID: PMC3480517  PMID: 22837378
chronic obstructive pulmonary disease; single-nucleotide polymorphism; genes
Respiratory medicine  2009;103(10):1468-1476.
To develop a more age-appropriate spirometric definition of chronic obstructive pulmonary disease (COPD) among older persons.
Using data from the Third National Health and Nutrition Examination Survey (NHANES III), we developed a two-part spirometric definition of COPD in older persons, aged 65–80 years, that 1) determines a cut-point for the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) based on mortality risk; and 2) among persons below this critical FEV1/FVC threshold, determines cut-points for the FEV1, expressed as a standardized residual percentile (SR-tile) and based on the prevalence of respiratory symptoms and mortality risk. Measurements included spirometry, health questionnaires, and mortality (National Death Index).
There were 2,480 older participants with a mean age of 71.7 years; 1,372 (55.4%) had a smoking history, 1,097 (44.2%) had respiratory symptoms and, over the course of 12-years, 868 (35.0%) had died. Among participants with an FEV1/FVC < .70 and FEV1 < 5th SR-tile, representing 7.7% of the cohort, the risk of death was doubled (adjusted hazard ratio, 2.01; 95% confidence interval [CI], 1.60–2.54). Among participants with an FEV1/FVC < .70 and FEV1 < 10th SR-tile, representing 13.4% of the cohort, the prevalence of respiratory symptoms was elevated (adjusted odds ratio, 2.44; CI, 1.79–3.33).
In a large, nationally representative sample of community-living older persons, defining COPD based on an FEV1/FVC < .70, with FEV1 cut-points at the 10th and 5th SR-tile, identifies individuals with an increased prevalence of respiratory symptoms and an increased risk of death, respectively.
PMCID: PMC2739264  PMID: 19464159
COPD; spirometry; respiratory symptoms; mortality
Yonsei Medical Journal  2012;53(2):363-368.
A new spirometric reference equation was recently developed from the first national chronic obstructive pulmonary disease (COPD) survey in Korea. However, Morris' equation has been preferred for evaluating spirometric values instead. The objective of this study was to evaluate changes in severity staging in Korean COPD patients by adopting the newly developed Korean equation.
Materials and Methods
We evaluated the spirometric data of 441 COPD patients. The presence of airflow limitation was defined as an observed post-bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) less than 0.7, and the severity of airflow limitation was assessed according to GOLD stages. Spirometric values were reassessed using the new Korean equation, Morris' equation and other reference equations.
The severity of airflow limitation was differently graded in 143 (32.4%) patients after application of the new Korean equation when compared with Morris' equation. All 143 patients were reallocated into more severe stages (49 at mild stage, 65 at moderate stage, and 29 at severe stage were changed to moderate, severe and very severe stages, respectively). Stages according to other reference equations were changed in 18.6-49.4% of the patients.
These results indicate that equations from different ethnic groups do not sufficiently reflect the airflow limitation of Korean COPD patients. The Korean reference equation should be used for Korean COPD patients in order to administer proper treatment.
PMCID: PMC3282976  PMID: 22318825
Spirometry; reference equation; COPD; diagnosis; stage
Chronic obstructive pulmonary disease (COPD) is frequently under-recognized and underdiagnosed. To determine the natural history of recognized and unrecognized COPD, we studied the rate of diagnosis, health care utilization, and mortality in patients with airflow limitation (AFL). Three hundred forty-seven outpatients at the Cincinnati Veterans Administration Medical Center performed spirometry and completed a respiratory questionnaire. Patients were followed for a minimum of 30 months and medical records were reviewed for COPD diagnosis, mortality, respiratory-related health care utilization, comorbidities, and respiratory medications. Three hundred twenty-five of 347 (94%) patients performed technically adequate spirometry and completed questionnaires. When AFL was defined by fixed ratio (FR, forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] < 0.7), patients with AFL and a diagnosis of COPD had a higher annual mortality rate (7.1% ± 2% versus 2.4% ± 0.8%, P = 0.01), more hospitalizations per year (0.2 ± 0.06 versus 0.04 ± 0.01, P < 0.001 mean ± standard error of the mean), increased respiratory symptoms (12.0 ± 0.9 versus 7.2 ± 0.6, P < 0.0001), and higher Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage compared with undiagnosed patients. Ninety-two of 137 patients with AFL (67%) had unrecognized AFL; 16 (17%) of the 92 were subsequently diagnosed. When AFL was defined by the lower limit of normal (LLN, FEV1/FVC < LLN), 67 of 103 patients (65%) had unrecognized AFL; 12 (18%) of the 67 were subsequently diagnosed. Patients with AFL defined by FR who were subsequently diagnosed had more emergency department visits per year (0.33 ± 0.11 versus 0.11 ± 0.05, P = 0.009), increased respiratory symptoms (10.2 ± 1.6 versus 6.5 ± 0.7, P < 0.05), and higher GOLD stage, but similar mortality and hospitalizations compared with the persistently undiagnosed patients. The annual rate of documented COPD diagnosis was 7% for both FR and LLN definitions. Patients with AFL and a diagnosis of COPD have more severe disease, higher health care utilization, and mortality than undiagnosed patients. The annual rate of COPD diagnosis is 7% among individuals with unrecognized AFL. Worse AFL, increased respiratory symptoms, and ED visits are associated with a subsequent COPD diagnosis in individuals with unrecognized AFL.
PMCID: PMC3634319  PMID: 23637527
COPD; diagnosis; airflow limitation; Veterans Healthcare Administration
Journal of Korean Medical Science  2009;24(4):621-626.
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.
PMCID: PMC2719218  PMID: 19654942
Pulmonary Disease, Chronic Obstructive; National Prevalence; Lower Limit of Normal; Spirometry
Yonsei Medical Journal  2014;55(4):980-986.
In clinical practice, some patients with asthma show incompletely reversible airflow obstruction, resembling chronic obstructive pulmonary disease (COPD). The aim of this study was to analyze this overlap phenotype of asthma with COPD feature.
Materials and Methods
A total of 256 patients, over the age of 40 years or more with a diagnosis of asthma, based on either 1) positive response to bronchodilator: >200 mL forced expiratory volume in 1 s (FEV1) and >12% baseline or 2) positive methacholine or mannitol provocation test, were enrolled. Among the asthma patients, we defined the overlap group with incompletely reversible airflow obstruction [postbronchodilator FEV1/forced vital capacity (FVC) <70] at the initial time of admission and continuing airflow obstruction after at least 3 months follow up. We evaluated clinical features, serum eosinophil counts, serum total immunoglobulin (Ig) E with allergy skin prick test, spirometry, methacholine or mannitol provocation challenges and bronchodilator responses, based on their retrospective medical record data. All of the tests mentioned above were performed within one week.
The study population was divided into two groups: asthma only (62%, n=159, postbronchodilator FEV1/FVC ≥70) and overlap group (38%, n=97, postbronchodilator FEV1/FVC <70). The overlap group was older, and contained more males and a higher percentage of current or ex-smokers than the asthma only group. Significantly lower FEV1 and higher total lung capacity, functional residual capacity, and residual volume were observed in the overlap group. Finally, significantly lower serum eosinophil count and higher IgE were seen in the overlap group.
Our results showed that the overlap phenotype was older, male asthmatic patients who have a higher lifetime smoking intensity, more atopy and generally worse lung function.
PMCID: PMC4075403  PMID: 24954327
Asthma; chronic obstructive pulmonary disease; overlap; airway hyperresponsiveness
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. However, much of the disease burden remains undiagnosed.
To compare the yield and cost effectiveness of two COPD case-finding approaches in primary care.
Design and setting
Pilot randomised controlled trial in two general practices in the West Midlands, UK.
A total of 1634 ever-smokers aged 35–79 years with no history of COPD or asthma were randomised into either a ‘targeted’ or ‘opportunistic’ case-finding arm. Respiratory questionnaires were posted to patients in the ‘targeted’ arm and provided to patients in the ‘opportunistic’ arm at routine GP appointments. Those reporting at least one chronic respiratory symptom were invited for spirometry. COPD was defined as pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC)<0.7 and FEV1<80% of predicted. Primary outcomes were the difference in the proportion of patients diagnosed with COPD and the cost per case detected.
Twenty-six per cent (212/815) in the ‘targeted’ and 13.6% (111/819) in the ‘opportunistic’ arm responded to the questionnaire and 78.3% (166/212) and 73.0% (81/111), respectively, reported symptoms; 1.2% (10/815) and 0.7% (6/819) of patients in the ‘targeted’ and ‘opportunistic’ arms were diagnosed with COPD (difference in proportions = 0.5% [95% confidence interval {CI} = –0.5% to 3.08%]). Over a 12-month period, the ‘opportunistic’ case-finding yield could be improved to 1.95% (95% CI = 1.0% to 2.9%). The cost-per case detected was £424.56 in the ‘targeted’ and £242.20 in the ‘opportunistic’ arm.
Opportunistic case finding may be more effective and cost effective than targeting patients with a postal questionnaire alone. A larger randomised controlled trial with adequate sample size is required to test this.
PMCID: PMC3529293  PMID: 23336474
chronic obstructive pulmonary disease; early detection of disease; primary care; randomised controlled trial; signs and symptoms; respiratory
This study was aimed to assess the pulmonary function tests (PFTs) in cardiac patients; with ischemic or rheumatic heart diseases as well as in patients who underwent coronary artery bypass graft (CABG) or valvular procedures. For the forty eligible participants, the pulmonary function was measured using the spirometry test before and after the cardiac surgery. Data collection sheet was used for the patient’s demographic and intra-operative information. Cardiac diseases and surgeries had restrictive negative impact on PFTs. Before surgery, vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), ratio between FEV1 and FVC, and maximum voluntary ventilation (MVV) recorded lower values for rheumatic patients than ischemic patients (P values were 0.01, 0.005, 0.0001, 0.031, and 0.035, respectively). Moreover, patients who underwent valvular surgery had lower PFTs than patients who underwent CABG with significant differences for VC, FVC, FEV1, and MVV tests (P values were 0.043, 0.011, 0.040, and 0.020, respectively). No definite causative factor appeared to be responsible for those results although mechanical deficiency and incisional chest pain caused by cardiac surgery are doubtful. More comprehensive investigation is required to resolve the case.
PMCID: PMC3727555  PMID: 23960642
Pulmonary complications; Cardiac surgery; Cardiac disease; Spirometry; Mechanics of respiration
In China, the burden of chronic obstructive disease (COPD) is high in never-smokers but little is known about its causes in this group.
We analysed data on 287 000 female and 30 000 male never-smokers aged 30–79 years from 10 regions in China, who participated in the China Kadoorie Biobank baseline survey (2004–2008). Prevalence of airflow obstruction (AFO) (pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and below the lower limit of normal (LLN)) was estimated, by age and region. Cross-sectional associations of AFO (FEV1/FVC <0.7), adjusted for confounding, were examined.
AFO prevalence defined as FEV1/FVC <0.7 was 4.0% in females and 5.1% in males (mean ages 51 and 54 years, respectively). AFO prevalence defined as FEV1/FVC
AFO is prevalent in Chinese never-smokers, particularly among those with low socioeconomic status or prior tuberculosis, and in rural males.
Airflow obstruction is prevalent in Chinese never-smokers and particularly associated with low socioeconomic status
PMCID: PMC4076527  PMID: 24603814
People with known risk factors for chronic obstructive pulmonary disease (COPD) are important targets for screening and early intervention. We sought to measure the prevalence of COPD among such individuals visiting a primary care practitioner for any reason. We also evaluated the accuracy of prior diagnosis or nondiagnosis of COPD and identified associated clinical characteristics.
We recruited patients from three primary care sites who were 40 years or older and had a smoking history of at least 20 pack-years. Participants were asked about respiratory symptoms and underwent postbronchodilator spirometry. COPD was defined as a ratio of forced expiratory volume in the first second of expiration to forced vital capacity (FEV1/FVC) of less than 0.7 and an FEV1 of less than 80% predicted.
Of the 1459 patients who met the study criteria, 1003 (68.7%) completed spirometry testing. Of these, 208 were found to have COPD, for a prevalence of 20.7% (95% confidence interval 18.3%–23.4%). Of the 205 participants with COPD who completed the interview about respiratory symptoms before spirometry, only 67 (32.7%) were aware of their diagnosis before the study. Compared with patients in whom COPD had been correctly diagnosed before the study, those in whom COPD had been over-diagnosed or undiagnosed were similar in terms of age, sex, current smoking status and number of visits to a primary care practitioner because of a respiratory problem.
Among adult patients visiting a primary care practitioner, as many as one in five with known risk factors met spirometric criteria for COPD. Underdiagnosis of COPD was frequent, which suggests a need for greater screening of at-risk individuals. Knowledge of the prevalence of COPD will help plan strategies for disease management.
PMCID: PMC2855915  PMID: 20371646
Journal of Thoracic Disease  2012;4(Suppl 1):AB20.
In patients with COPD, there is an evidence of platelet activation due to chronic hypoxia and systemic inflammation. Aim of the study was to evaluate Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW), markers of platelet activation, in patients with Chronic Obstructive Pulmonary Disease (COPD), and to investigate possible associations with pulmonary function testing [Forced expiratory volume in 1 second (FEV1) and Forced vital capacity (FVC)].
Patients and methods
Current smokers with stable COPD (n=85) and smokers without airflow limitation (n=35) were included. To all of them pulmonary function testing was performed and count of white blood cells (WBC) platelets, as well as MPV and PDW were measured.
In smokers with COPD, MPV was significantly higher (mean value 10.563±1.531 vs. 9.956±1.046 fl, P<0.05) than in control group. WBC was also significantly higher in patients with COPD than in controls (9045.53±2664.34/μL vs. 7018.79±1989.74/μL, P<0.001). A significant correlation between MPV and WBC in COPD patients was revealed, especially in those at GOLD Stage III (r=0.475, P=0.012) and IV (r=0.367, P=0.033). WBC count was correlated with FEV1/FVC values (P=0.044). MPV did not correlate with any indices of COPD severity.
In patients with COPD, MPV and WBC levels are significantly correlated and are elevated in comparison to smokers with normal pulmonary function. WBC count was negatively correlated with FEV1/FVC values.
PMCID: PMC3537346
The best method for expressing lung function impairment is undecided. We tested in a population of patients with chronic obstructive pulmonary disease (COPD) whether forced expiratory volume in 1 second (FEV1) or FEV1 divided by height squared (FEV1/ht2) was better than FEV1 percent predicted (FEV1PP) for predicting survival.
FEV1, FEV1PP, and FEV1/ht2 recorded post bronchodilator were compared as predictors of survival in 1095 COPD patients followed for 15 years. A staging system for severity of COPD was defined from FEV1/ht2 and compared with the Global Initiative for Obstructive Lung Disease (GOLD) staging system.
FEV1/ht2 was a better univariate predictor of survival in COPD than FEV1 and both were better than FEV1PP. The best multivariate model for predicting survival included FEV1/ht2, age and sex. Comparing the GOLD stages with the FEV1/ht2 groups found that survival was more coherent within each FEV1/ht group than it was within each GOLD stage. FEV1/ht2 had 60% more people in its most severe group than the severest GOLD stage with these extra subjects having equivalently poor survival and had 155% more in the least severe group with equivalent survival. GOLD staging misclassified 51% of subjects with regard to survival.
We conclude that GOLD criteria using FEV1PP do not optimally stage COPD with regard to survival. An alternative strategy using FEV1/ht2 improves the staging of this disease. Studies which stratify COPD patients to determine the effect of interventions such as drug trials, rehabilitation, or management guidelines should consider alternatives to the GOLD classification.
PMCID: PMC2699963  PMID: 18268941
chronic obstructive pulmonary disease; spirometry; respiratory function tests
Thorax  2003;58(5):388-393.
Background: A study was undertaken to define the risk of death among a national cohort of US adults both with and without lung disease.
Methods: Participants in the first National Health and Nutrition Examination Survey (NHANES I) followed for up to 22 years were studied. Subjects were classified using a modification of the Global Initiative for Chronic Obstructive Lung Disease criteria for chronic obstructive pulmonary disease (COPD) into the following mutually exclusive categories using the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and the presence of respiratory symptoms: severe COPD, moderate COPD, mild COPD, respiratory symptoms only, restrictive lung disease, and no lung disease. Proportional hazard models were developed that controlled for age, race, sex, education, smoking status, pack years of smoking, years since quitting smoking, and body mass index.
Results: A total of 1301 deaths occurred in the 5542 adults in the cohort. In the adjusted proportional hazards model the presence of severe or moderate COPD was associated with a higher risk of death (hazard ratios (HR) 2.7 and 1.6, 95% confidence intervals (CI) 2.1 to 3.5 and 1.4 to 2.0), as was restrictive lung disease (HR 1.7, 95% CI 1.4 to 2.0).
Conclusions: The presence of both obstructive and restrictive lung disease is a significant predictor of earlier death in long term follow up.
PMCID: PMC1746680  PMID: 12728157
Thorax  2009;64(11):944-949.
A study was undertaken to determine if quantitative CT estimates of lung parenchymal overinflation and airway dimensions in smokers with a normal forced expiratory volume in 1 s (FEV1) can predict the rapid decline in FEV1 that leads to chronic obstructive pulmonary disease (COPD).
Study participants (n = 143; age 45–72 years; 54% male) were part of a lung cancer screening trial, had a smoking history of >30 pack years and a normal FEV1 and FEV1/forced vital capacity (FVC) at baseline (mean (SD) FEV1 99.4 (12.8)%, range 80.2–140.7%; mean (SD) FEV1/FVC 77.9 (4.4), range 70.0–88.0%). An inspiratory multislice CT scan was acquired for each subject at baseline. Custom software was used to measure airway lumen and wall dimensions; the percentage of the lung inflated beyond a predicted maximal lung inflation, the low attenuation lung area with an x ray attenuation lower than −950 HU and the size distribution of the overinflated lung areas and the low attenuation area were described using a cluster analysis. Multiple regression analysis was used to test the hypothesis that these CT measurements combined with other baseline characteristics might identify those who would develop an excessive annual decline in FEV1.
The mean (SD) annual change in FEV1 was −2.3 (4.7)% predicted (range −23.0% to +8.3%). Multiple regression analysis revealed that the annual change in FEV1%predicted was significantly associated with baseline percentage overinflated lung area measured on quantitative CT, FEV1%predicted, FEV1/FVC and gender.
Quantitative CT scan evidence of overinflation of the lung predicts a rapid annual decline in FEV1 in smokers with normal FEV1.
PMCID: PMC3035577  PMID: 19734130
British Medical Journal  1977;1(6077):1645-1648.
A prospective epidemiological study of the early stages of the development of chronic obstructive pulmonary disease was performed on London working men. The findings showed that forced expiratory volume in one second (FEV1) falls gradually over a lifetime, but in most non-smokers and many smokers clinically significant airflow obstruction never develops. In susceptible people, however, smoking causes irreversible obstructive changes. If a susceptible smoker stops smoking he will not recover his lung function, but the average further rates of loss of FEV1 will revert to normal. Therefore, severe or fatal obstructive lung disease could be prevented by screening smokers' lung function in early middle age if those with reduced function could be induced to stop smoking. Infective processes and chronic mucus hypersecretion do not cause chronic airflow obstruction to progress more rapidly. There are thus two largely unrelated disease processes, chronic airflow obstruction and the hypersecretory disorder (including infective processes).
PMCID: PMC1607732  PMID: 871704
Thorax  2002;57(9):759-764.
Background: Patients with chronic obstructive pulmonary disease (COPD) are prone to frequent exacerbations which are a significant cause of morbidity and mortality. Stable COPD patients often have lower airway bacterial colonisation which may be an important stimulus to airway inflammation and thereby modulate exacerbation frequency.
Methods: Twenty nine patients with COPD (21 men, 16 current smokers) of mean (SD) age 65.9 (7.84) years, forced expiratory volume in 1 second (FEV1) 1.06 (0.41) l, FEV1 % predicted 38.7 (15.2)%, FEV1/FVC 43.7 (14.1)%, inhaled steroid dosage 1.20 (0.66) mg/day completed daily diary cards for symptoms and peak flow over 18 months. Exacerbation frequency rates were determined from diary card data. Induced sputum was obtained from patients in the stable state, quantitative bacterial culture was performed, and cytokine levels were measured.
Results: Fifteen of the 29 patients (51.7%) were colonised by a possible pathogen: Haemophilus influenzae (53.3%), Streptococcus pneumoniae (33.3%), Haemophilus parainfluenzae (20%), Branhamella catarrhalis (20%), Pseudomonas aeruginosa (20%). The presence of lower airway bacterial colonisation in the stable state was related to exacerbation frequency (p=0.023). Patients colonised by H influenzae in the stable state reported more symptoms and increased sputum purulence at exacerbation than those not colonised. The median (IQR) symptom count at exacerbation in those colonised by H influenzae was 2.00 (2.00–2.65) compared with 2.00 (1.00–2.00) in those not colonised (p=0.03). The occurrence of increased sputum purulence at exacerbation per patient was 0.92 (0.56–1.00) in those colonised with H influenzae and 0.33 (0.00–0.60) in those not colonised (p=0.02). Sputum interleukin (IL)-8 levels correlated with the total bacterial count (rho=0.459, p=0.02).
Conclusion: Lower airway bacterial colonisation in the stable state modulates the character and frequency of COPD exacerbations.
PMCID: PMC1746426  PMID: 12200518
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.
PMCID: PMC2571721  PMID: 8426385
Background:Metabolic syndrome (Mets) is reportedly associated with chronic obstructive pulmonary disease (COPD). However, the relationship between abdominal circumference (AC) and decline in FEV1 has not been elucidated. We aimed to investigate this relationship among male current smokers.
Methods:Spirometry was performed on subjects (n = 3,257) ≥ 40 years of age, who participated in a community-based annual health check in Takahata, Japan, from 2004 through 2006 (visit 1). Spirometry was re-evaluated, and AC was assessed in 147 of the male current smokers in 2009 (visit 2). The diagnosis of Mets was based on the criteria used in the Hisayama Study.
Results:No significant relationships were observed between AC and spirometric parameters such as % predicted forced vital capacity (FVC), % predicted forced expiratory volume in 1 s (FEV1) and FEV1/FVC. However, decline in FEV1 was significantly correlated with AC. Multivariate logistic regression analysis showed that AC was a significant discriminating factor for decline in FEV1, independently of age, Brinkman index and change in body mass index from visit 1 to visit 2. At visit 2, there was a greater prevalence of decline in FEV1 among subjects with Mets (n=17) than among those without Mets. Although there were no differences in % predicted FVC, % predicted FEV1 or FEV1/FVC between subjects with or without Mets, the rate of decline in FEV1 was significantly greater in subjects with Mets than in those without.
Conclusions:This retrospective analysis suggested that measuring AC may be useful for discriminating male smokers who show a decline in FEV1.
PMCID: PMC3534871  PMID: 23288999
decline in FEV1; abdominal circumference; smoker; health check.
The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease. The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV. Few data on FEV1 decline are available for GOLD stage I. Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD. To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages.
PMCID: PMC3282601  PMID: 22371650
chronic obstructive pulmonary disease; decline; forced expiratory volume in 1 second; FEV1
BMC Medical Genetics  2007;8(Suppl 1):S8.
Pulmonary function measures obtained by spirometry are used to diagnose chronic obstructive pulmonary disease (COPD) and are highly heritable. We conducted genome-wide association (GWA) analyses (Affymetrix 100K SNP GeneChip) for measures of lung function in the Framingham Heart Study.
Ten spirometry phenotypes including percent of predicted measures, mean spirometry measures over two examinations, and rates of change based on forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow from the 25th to 75th percentile (FEF25–75), the FEV1/FVC ratio, and the FEF25–75/FVC ratio were examined. Percent predicted phenotypes were created using each participant's latest exam with spirometry. Predicted lung function was estimated using models defined in the set of healthy never-smokers, and standardized residuals of percent predicted measures were created adjusting for smoking status, pack-years, and body mass index (BMI). All modeling was performed stratified by sex and cohort. Mean spirometry phenotypes were created using data from two examinations and adjusting for age, BMI, height, smoking and pack-years. Change in pulmonary function over time was studied using two to four examinations with spirometry to calculate slopes, which were then adjusted for age, height, smoking and pack-years.
Analyses were restricted to 70,987 autosomal SNPs with minor allele frequency ≥ 10%, genotype call rate ≥ 80%, and Hardy-Weinberg equilibrium p-value ≥ 0.001. A SNP in the interleukin 6 receptor (IL6R) on chromosome 1 was among the best results for percent predicted FEF25–75. A non-synonymous coding SNP in glutathione S-transferase omega 2 (GSTO2) on chromosome 10 had top-ranked results studying the mean FEV1 and FVC measurements from two examinations. SNPs nearby the SOD3 and vitamin D binding protein genes, candidate genes for COPD, exhibited association to percent predicted phenotypes.
GSTO2 and IL6R are credible candidate genes for association to pulmonary function identified by GWA. These and other observed associations warrant replication studies. This resource of GWA results for pulmonary function measures is publicly available at .
PMCID: PMC1995616  PMID: 17903307
Background and objectives
Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) commonly coexist and share common risk factors. The prevalence of COPD in outpatients with a smoking history and CVD in Japan is unknown. The aim of this study was to determine the proportion of Japanese patients with a smoking history being treated for CVD who have concurrent airflow limitation compatible with COPD. A secondary objective was to test whether the usage of lung function tests performed in the clinic influenced the diagnosis rate of COPD in the patients identified with airflow limitation.
In a multicenter observational prospective study conducted at 17 centers across Japan, the prevalence of airflow limitation compatible with COPD (defined as forced expiratory volume (FEV)1/FEV6 <0.73, by handheld spirometry) was investigated in cardiac outpatients ≥40 years old with a smoking history who routinely visited the clinic for their CVD. Each patient completed the COPD Assessment Test prior to spirometry testing.
Data were available for 995 patients with a mean age of 66.6±10.0 years, of whom 95.5% were male. The prevalence of airflow limitation compatible with COPD was 27.0% (n=269), and 87.7% of those patients (n=236) did not have a prior diagnosis of COPD. The prevalence of previously diagnosed airflow limitation was higher in sites with higher usage of lung function testing (14.0%, 15.2% respectively) compared against sites where it is performed seldom (11.1%), but was still low.
The prevalence of airflow limitation in this study indicates that a quarter of outpatients with CVD have COPD, almost all of whom are undiagnosed. This suggests that it is important to look routinely for COPD in CVD outpatients.
PMCID: PMC4044996  PMID: 24920894
COPD; CVD; handheld spirometer; lung function; diagnosis

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