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
Adult; chronic obstructive pulmonary disease; epidemiology
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.
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.
COPD; spirometry; respiratory symptoms; mortality
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.
Spirometry; reference equation; COPD; diagnosis; stage
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.
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.
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.
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 .
Cigarette smoking and advanced age are well known as risk factors for chronic obstructive pulmonary disease (COPD), and nutritional abnormalities are important in patients with COPD. However, little is known about the nutritional status in non-COPD aging men with smoking history. We therefore investigated whether reduced lung function is associated with lower blood markers of nutritional status in those men.
Subjects and methods:
This association was examined in a cross-sectional study of 65 Japanese male current or former smokers aged 50 to 80 years: 48 without COPD (non-COPD group), divided into tertiles according to forced expiratory volume in one second as percent of forced vital capacity (FEV1/FVC), and 17 with COPD (COPD group).
After adjustment for potential confounders, lower FEV1/FVC was significantly associated with lower red blood cell count (RBCc), hemoglobin, and total protein (TP); not with total energy intake. The difference in adjusted RBCc and TP among the non-COPD group tertiles was greater than that between the bottom tertile in the non-COPD group and the COPD group.
In non-COPD aging men with smoking history, trends toward reduced nutritional status and anemia may independently emerge in blood components along with decreased lung function even before COPD onset.
anemia; chronic obstructive pulmonary disease; lung function; nutritional assessment; nutritional status; smoking
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.
decline in FEV1; abdominal circumference; smoker; health check.
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.
Pulmonary Disease, Chronic Obstructive; National Prevalence; Lower Limit of Normal; Spirometry
Chronic obstructive pulmonary disease (COPD) encompasses a group of disorders characterised by the presence of incompletely reversible airflow obstruction with overlapping subsets of different phenotypes including chronic bronchitis, emphysema or asthma. The aim of this study was to determine the proportion of adult subjects aged >50 years within each phenotypic subgroup of COPD, defined as a post-bronchodilator ratio of forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7, in accordance with current international guidelines.
Adults aged >50 years derived from a random population-based survey undertook detailed questionnaires, pulmonary function tests and chest CT scans. The proportion of subjects in each of 16 distinct phenotypes was determined based on combinations of chronic bronchitis, emphysema and asthma, with and without incompletely reversible airflow obstruction defined by a post-bronchodilator FEV1/FVC ratio of 0.7.
A total of 469 subjects completed the investigative modules, 96 of whom (20.5%) had COPD. Diagrams were constructed to demonstrate the relative proportions of the phenotypic subgroups in subjects with and without COPD. 18/96 subjects with COPD (19%) had the classical phenotypes of chronic bronchitis and/or emphysema but no asthma; asthma was the predominant COPD phenotype, being present in 53/96 (55%). When COPD was defined as a post-bronchodilator FEV1/FVC less than the lower limit of normal, there were one-third fewer subjects with COPD and a smaller proportion without a defined emphysema, chronic bronchitis or asthma phenotype.
This study provides proportional classifications of the phenotypic subgroups of COPD which can be used as the basis for further research into the pathogenesis and treatment of this heterogeneous disorder.
Among older persons, we previously endorsed a two-step spirometric definition of chronic obstructive pulmonary disease (COPD) that requires a ratio of forced expiratory volume in 1-second to forced vital capacity (FEV1/FVC) below .70, and an FEV1 below the 5th or 10th standardized-residual percentile (“SR-tile strategy”).
To evaluate the clinical validity of an SR-tile strategy, compared to a current definition of COPD, as published by the Global Initiative for Obstructive Lung Disease (GOLD-COPD), in older persons.
We assessed national data from 2,480 persons aged 65-to-80 years. In separate analyses, we evaluated the association of an SR-tile strategy with mortality and respiratory symptoms, relative to GOLD-COPD. As per convention, GOLD-COPD was defined solely by an FEV1/FVC<.70, with severity staged according to FEV1 cut-points at 80 and 50 percent-predicted (%Pred).
Among 831 participants with GOLD-COPD, the risk of death was elevated only in 179 (21.5%) of those who also had an FEV1 <5thSR-tile; and the odds of having respiratory symptoms was elevated only in 310 (37.4%) of those who also had an FEV1 <10thSR-tile. In contrast, GOLD-COPD staged at an FEV1 50-79%Pred led to misclassification (overestimation) in terms of 209 (66.4%) and 77 (24.6%) participants, respectively, not having an increased risk of death or likelihood of respiratory symptoms.
Relative to an SR-tile strategy, the majority of older persons with GOLD-COPD had neither an increased risk of death nor an increased likelihood of respiratory symptoms. These results raise concerns about the clinical validity of GOLD guidelines in older persons.
COPD; spirometry; respiratory symptoms; mortality
The objective of this paper is to provide an overview of the recent developments in muscle physiology and biochemistry in general, and with respect to chronic obstructive pulmonary disease (COPD) specifically. As a way of illustration, we have presented data on the remodeling that occurs in vastus lateralis in two patients with COPD (COPD #1, forced expiratory volume in one second/forced vital capacity [FEV1/FVC] = 63%; COPD #2, FEV1/FVC = 41%) exhibiting differences in muscle wasting as compared to healthy controls (CON; FEV1/FVC = 111 ± 2.2%, n = 4). Type I fibers percentages were lower in both COPD #1 (16.7) and COPD #2 (24.9) compared to CON (57.3 ± 5.2). Cross sectional area of the type I fibers of the patients ranged between 65%–68% of CON and for the type II subtypes (IIA, IIAX, IIX) between 74% and 89% (COPD #1) and 17%–32% (COPD #2). A lower number of capillary contacts were observed for all fiber types in COPD #1 but not COPD #2. Lower concentrations of adenosine triphosphate (ATP) (24%–26%) and phosphocreatine (18%–20%), but not lactate occurred in COPD. In contrast to COPD #1, who displayed normal glucose transporter content, GLUT1 and GLUT4 were only 71% and 54%, respectively of CON in COPD #2. Lower monocarboxylate contents were found for MCT1 in both COPD #1 (63%) and COPD #2 (41%) and for MCT4 (78%) in COPD #1. Maximal oxidative enzyme activities (Vmax) for COPD #2 ranged between 37% (succinic dehydrogenase) and 70% (cytochrome C oxidase) of CON. For the cytosolic enzymes, Vmax ranged between 89% (hexokinase) to 31% (pyruvate kinase) of CON. Depressions were also observed in Vmax of the Na+-K+-ATPase for COPD #1 (66% of CON) but not COPD #2 (92% of CON) while Vmax of the Ca2+-ATPase was near normal in COPD #1 (84% CON). It is concluded that disturbances can occur in muscle to a wide range of excitation, contraction and metabolic processes in COPD.
vastus lateralis; fiber types; area; capillarization; metabolism; enzymatic pathways; excitation-contraction processes; glucose and monocarboxylate transporters
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.
Many studies have investigated angina and its relationship with chronic obstructive pulmonary disease (COPD). However, angina was diagnosed only by noninvasive tests or only by clinical symptoms in most of these studies. The aim of this study was to compare the prognosis, including rate of hospitalization and death from significant coronary artery lesion and nonsignificant coronary artery lesion angina, in patients with COPD.
Patients with COPD who underwent coronary angiography (CAG) due to angina were reviewed retrospectively at a tertiary referral hospital. COPD is defined as post-bronchodilator forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC) of < 70%. A significant coronary lesion is defined as at least 50% diameter stenosis of one major epicardial artery in CAG.
In total, 113 patients were enrolled. Mean follow-up duration was 39 ± 21 months. Of the patients, 52 (46%) had mild COPD and 48 (42%) had moderate COPD. Sixty-nine (61%) patients had significant stenosis in CAG. The death rate in the follow-up period was 2.21 per 100 patient-years. No significant difference was observed among the all-cause mortality rate, admission rate, or intensive care unit admission rate in patients who had COPD with or without significant coronary artery disease. Pneumonia or acute exacerbation of COPD was the most common cause of admission.
In patients having COPD with angina who underwent CAG, no significant difference was observed in mortality or admission events depending on the presence of a significant coronary artery lesion during the 2-year follow-up period.
Pulmonary disease, chronic obstructive; Coronary angiography; Coronary stenosis
Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n ≤ 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10−12), 4q24 in GSTCD (2.18 × 10−23), 5q33 in HTR4 (P = 4.29 × 10−9), 6p21 in AGER (P = 3.07 × 10−15) and 15q23 in THSD4 (P = 7.24 × 10−15). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
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.
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.
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease (COPD) uses the post-bronchodilator spirometry for diagnosis and severity staging. We evaluated differences in the severity classification of COPD, based on pre- and post-bronchodilator spirometry.
Materials and Methods
From 2000 to 2004, 207 COPD patients who underwent spirometry before and after inhalation of 400 µg of fenoterol were analyzed. A responder to the bronchodilator test (BDT) was defined by the American Thoracic Society (ATS) as an increase in forced expiratory volume in one second (FEV1) or forced vital capacity ≥ 12% and ≥ 200 mL, and by the European Respiratory Society (ERS) as an increase in FEV1 ≥ 10% of the predicted value. COPD severity was classified according to the 2008 GOLD guidelines.
For the entire study population, the FEV1 increased by 11.8 ± 12.5% of baseline after BDT and 41.1% and 27.1% of subjects were classified as responders using the ATS and ERS criteria, respectively. Based on pre-BDT spirometry, 55, 85, 58, and 9 patients were classified as Stage I-IV COPD, respectively. Sixty-seven (32.4%) patients changed severity staging after BDT, including 20.0%, 28.2%, 44.8%, and 66.7% of pre-BDT patients Stages I through IV, respectively. More ATS or ERS BDT-responders had a change in severity staging than non-responders (52.9% vs. 18.9% and 62.5% vs. 21.2%, both p < 0.001).
Our data suggest that the severity staging of COPD using pre-BDT spirometry might lead to significant differences as compared to staging, based on post-BDT spirometry, as recommended by the current GOLD guidelines.
Bronchodilator test; chronic obstructive pulmonary disease; severity staging
The purpose of this study was to evaluate the relationship of pulmonary function impairment (PFI) and coronary artery calcification (CAC) by multi-detector computed tomography (MDCT), and the effect of pneumoconiosis on CAC or PFI.
Seventy-six subjects exposed to inorganic dusts underwent coronary artery calcium scoring by MDCT, spirometry, laboratory tests, and a standardized questionnaire. CAC was quantified using a commercial software (Rapidia ver. 2.8), and all the subjects were divided into two categories according to total calcium scores (TCSs), either the non-calcified (<1) or the calcified (≥1) group. Obstructive pulmonary function impairment (OPFI) was defined as forced expiratory volume in one second/forced vital capacity (FEV1/FVC, %)<70, and as FEV1/FVC (%)≥70 and FVC<80 for restrictive pulmonary function impairment (RPFI) by spirometry. All subjects were classified as either the case (profusion≥1/0) or the control (profusion≤0/1) group by pneumoconiosis findings on simple digital radiograph.
Of the 76 subjects, 35 subjects (46.1%) had a CAC. Age and hypertension were different significantly between the non-calcified and the calcified group (p<0.05). Subjects with pneumoconiosis were more frequent in the calcified group than those in the non-calcified group (p=0.099). FEV1/FVC (%) was significantly correlated with TCSs (r=-0.316, p=0.005). Subjects with OPFI tended to increase significantly with increasing of TCS (4.82, p=0.028), but not significantly in RPFI (2.18, p=0.140). Subjects with OPFI were significantly increased in the case group compared to those in the control group.
CAC is significantly correlated with OPFI, and CAC and OPFI may be affected by pneumoconiosis findings.
Coronary Vessels; Vascular Calcification; Spirometry; Pneumoconiosis; Pulmonary Function Tests
BACKGROUND—It has been
suggested that oxidative stress is an important factor in the
pathogenesis of chronic obstructive pulmonary disease (COPD). We have
shown that an oxidant/antioxidant imbalance occurs in the distal air
spaces of smokers and in patients with COPD which is reflected
systemically in the plasma. A study was undertaken to determine whether
plasma antioxidant status correlated with lung function as assessed by
forced expiratory volume in one second (FEV1) and forced
vital capacity (FVC) in smokers and patients with COPD.
antioxidant capacity, assessed by the Trolox equivalent antioxidant
capacity (TEAC) as an index of overall systemic oxidative stress, and
protein thiol levels were measured in 95patients with stable COPD, in
82 healthy smokers, and in 37 healthy non-smokers.
plasma TEAC levels were significantly decreased in patients with COPD
(0.81 (0.03) mmol/l, p<0.001) and in healthy smokers (0.87 (0.04) mmol/l, p<0.001) compared with healthy non-smokers (1.31 (0.11) mmol/l). The mean differences in plasma antioxidant capacity
(mM) were (0.81, 95% confidence interval (CI) 0.22 to 1.48), (0.87, 95% CI 0.2 to 1.46), and (1.31, 95% CI 1.09 to 1.58) in patients with
COPD, healthy smokers, and healthy non-smokers, respectively. This
reduction was associated with a 29% (95% CI 18 to 38) and a 30%
(95% CI 19 to 40) decrease in plasma protein thiol levels in COPD
patients and smokers, respectively. Current smoking was not the main
contributor to the reduction in antioxidant capacity in patients with
COPD as those patients who were still smokers had similar TEAC levels
(mean (SE) 0.78 (0.05); n = 25) to those who had stopped smoking (0.84 (0.02); n = 70). No significant correlations were found between
spirometric data measured as FEV1 % predicted or
FEV1/FVC % predicted and the plasma levels of TEAC in
patients with COPD, healthy smokers, or healthy non-smokers. Similarly,
there was no significant correlation between FEV1 %predicted or FEV1/FVC % predicted and the levels of plasma
protein thiols in the three groups.
confirm decreased antioxidant capacity in smokers and patients with
COPD, indicating the presence of systemic oxidative stress. However, no
relationship was found between protein thiols or TEAC levels and
measurements of airflow limitation in either smokers or in patients
Systemic inflammation is associated with reduced lung function in both healthy individuals and those with chronic obstructive pulmonary disease (COPD). Whether systemic inflammation in healthy young adults is associated with future impairment in lung health is uncertain.
We evaluated the association between plasma fibrinogen and C-reactive protein (CRP) in young adults and lung function in the Coronary Artery Risk Development in Young Adults cohort study. Higher year 7 fibrinogen was associated with greater loss of forced vital capacity (FVC) between years 5 and 20 (439 mL in quartile 4 vs. 398 mL in quartile 1, P<0.001) and forced expiratory volume in 1 second (FEV1) (487 mL in quartile 4 vs. 446 mL in quartile 1, P<0.001) independent of cigarette smoking, body habitus, baseline lung function and demographic factors. Higher year 7 CRP was also associated with both greater loss of FVC (455 mL in quartile 4 vs. 390 mL in quartile 1, P<0.001) and FEV1 (491 mL in quartile 4 vs. 442 mL in quartile 1, P = 0.001). Higher year 7 fibrinogen and CRP were associated with abnormal FVC at year 20 (odds ratio (OR) per standard deviation 1.51 (95% confidence interval (CI): 1.30–1.75) for fibrinogen and 1.35 (95% CI: 1.14–1.59) for CRP). Higher year 5 fibrinogen was additionally associated with abnormal FEV1. A positive interaction was observed between pack-years cigarette smoking and year 7 CRP for the COPD endpoint, and among participants with greater than 10 pack-years of cigarette exposure, year 7 CRP was associated with greater odds of COPD at year 20 (OR per standard deviation 1.53 (95% CI: 1.08–2.16).
Systemic inflammation in young adults is associated with abnormal lung function in middle age. In particular, elevated CRP may identify vulnerability to COPD among individuals who smoke.
Measurements of lung function by spirometry are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important measures, forced expiratory volume in the first second (FEV1) and its ratio to forced vital capacity (FEV1/FVC), an indicator of airflow obstruction. This meta-analysis included 20,890 participants of European ancestry from four CHARGE consortium studies: Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health Study (CHS), Framingham Heart Study (FHS), and Rotterdam Study (RS). We identified eight loci associated with FEV1/FVC (HHIP, GPR126, ADAM19, AGER-PPT2, FAM13A, PTCH1, PID1, and HTR4) and one locus associated with FEV1 (INTS12-GSTCD-NPNT) at or near genome-wide significance (P<5×10−8) in CHARGE; all but 3 loci (FAM13A, PTCH1, and PID1) replicated with the SpiroMeta consortium. Our findings of novel loci influencing pulmonary function may offer insights into chronic lung disease pathogenesis.