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1.  The association between airflow obstruction and radiologic change by tuberculosis 
Journal of Thoracic Disease  2014;6(5):471-476.
Introduction
Cigarette smoking is the most commonly encountered risk factor for chronic obstructive pulmonary disease (COPD). However, it is not the only one and there is consistent evidence from epidemiologic studies that nonsmokers may develop chronic airflow limitation. A history of tuberculosis has recently been found to be associated with airflow obstruction in adults older than 40 years. The aim of this study was to evaluate the association between the radiologic changes by tuberculosis and airflow obstruction in a population based sample.
Methods
A nationwide COPD prevalence survey was conducted. We compared the prevalence of airflow obstruction according to the presence of the radiologic change by the tuberculosis.
Results
We analyzed 1,384 subjects who participated in the nationwide Korean COPD survey. All subjects were older than 40 years and took the spirometry and simple chest radiography. We defined the airflow obstruction as FEV1/FVC <0.7. A total of 149 (10.8%) subjects showed airflow obstruction. A total of 167 (12.1%) subjects showed radiologic change by tuberculosis. Among these 167 subjects, 44 (26.3%) had airflow obstruction. For the subjects without radiologic change by tuberculosis, the prevalence of airflow obstruction was only 8.6%. The unadjusted odds ratio for airflow obstruction according to the radiologic change was 3.788 (95% CI: 2.544-5.642).
Conclusions
The radiologic change by tuberculosis was associated with airflow obstruction.
doi:10.3978/j.issn.2072-1439.2014.04.02
PMCID: PMC4014992  PMID: 24822105
Chronic obstructive pulmonary disease (COPD); tuberculosis; risk factor; airflow obstruction
2.  Lung Function in Young Adults Predicts Airflow Obstruction 20 Years Later 
The American journal of medicine  2010;123(5):468.e1-468.e7.
Rationale
The burden of obstructive lung disease is increasing, yet there are limited data on its natural history in young adults.
Objectives
To determine in a prospective cohort of generally healthy young adults the influence of early adult lung function on the presence of airflow obstruction in middle age.
Methods
Longitudinal study of 2,496 adults who were 18-30 years of age at entry, did not report having asthma, and returned at Year 20. Airflow obstruction was defined as an FEV1/FVC ratio less than the lower limit of normal.
Measurements and Main Results
Airflow obstruction was present in 6.9% and 7.8% of participants at Years 0 and 20. Less than 10% of participants with airflow obstruction self-reported COPD. In cross sectional analyses airflow obstruction was associated with less education, smoking, and self-reported COPD. Low FEV1 and FEV1/FVC and airflow obstruction in young adults were associated with low lung function and airflow obstruction 20 years later. Of those with airflow obstruction at Year 0, 52% had airflow obstruction 20 years later. The FEV1/FVC at Year 0 was highly predictive of airflow obstruction 20 years later (c-statistic 0.91; 95% CI 0.89-0.93). The effect of cigarette smoking on lung function decline with age was most evident in young adults with pre-existing airflow obstruction.
Conclusions
Airflow obstruction is mostly unrecognized in young and middle age adults. A low FEV1, low FEV1/FVC and airflow obstruction in young adults, in addition to smoking, are highly predictive of low lung function and airflow obstruction in middle age.
doi:10.1016/j.amjmed.2009.07.037
PMCID: PMC2858051  PMID: 20399325
Airflow obstruction; CARDIA; chronic obstructive pulmonary disease; COPD; natural history
3.  Difference in airflow obstruction between Hispanic and non-Hispanic white female smokers 
COPD  2008;5(5):274-281.
Rationale
Smoking-related respiratory diseases are a major cause of morbidity and mortality. However, the relationship between smoking and respiratory disease has not been well-studied among ethnic minorities in general and among women in particular.
Objective
The objective of this cross-sectional study was to evaluate the risk of airflow obstruction and to assess lung function among Hispanic and non-Hispanic white (NHW) female smokers in a New Mexico cohort.
Methods
Participants completed a questionnaire detailing smoking history and underwent spirometry testing. Outcomes studied included airflow obstruction, selected lung function parameters, and chronic mucus hyper-secretion. Chi square, logistic, and linear regression techniques were utilized.
Main findings
Of the 1,433 eligible women participants, 248 (17.3%) were Hispanic; and 319 had airflow obstruction (22.3%). Hispanic smokers were more likely to be current smokers, and report lower pack-years of smoking, compared to NHW smokers (p < 0.05 for all analyses). Further, Hispanic smokers were at a reduced risk of airflow obstruction compared to NHW smokers, with an O.R. of 0.51, 95% C.I. 0.34, 0.78 (p = 0.002) after adjustment for age, BMI, pack-years and duration of smoking, and current smoking status. Following adjustment for covariates, Hispanic smokers also had a higher mean absolute and percent predicted post-bronchodilator FEV1/FVC ratio, as well as higher mean percent predicted FEV1 (p < 0.05 for all analyses).
Principal conclusions
Hispanic female smokers in this New Mexico-based cohort had lower risk of airflow obstruction and better lung function than NHW female smokers. Further, smoking history did not completely explain these associations.
doi:10.1080/15412550802363345
PMCID: PMC3616889  PMID: 18972275
Hispanic ethnicity; Smokers; Airflow obstruction; Pulmonary function; Chronic mucus hyper-secretion; Women
4.  Association of Radiographic Emphysema and Airflow Obstruction with Lung Cancer 
Rationale: To study the relationship between emphysema and/or airflow obstruction and lung cancer in a high-risk population.
Objective: We studied lung cancer related to radiographic emphysema and spirometric airflow obstruction in tobacco-exposed persons who were screened for lung cancer using chest computed tomography (CT).
Methods: Subjects completed questionnaires, spirometry, and low-dose helical chest CT. CT scans were scored for emphysema based on National Emphysema Treatment Trial criteria. Multiple logistic regressions estimated the independent associations between various factors, including radiographic emphysema and airflow obstruction, and subsequent lung cancer diagnosis.
Measurements and Main Results: Among 3,638 subjects, 57.5, 18.8, 14.6, and 9.1% had no, trace, mild, and moderate–severe emphysema, and 57.3, 13.6, 22.8, and 6.4% had no, mild (Global Initiative for Chronic Obstructive Lung Disease [GOLD] I), moderate (GOLD II), and severe (GOLD III–IV) airflow obstruction. Of 3,638 subjects, 99 (2.7%) received a lung cancer diagnosis. Adjusting for sex, age, years of cigarette smoking, and number of cigarettes smoked daily, logistic regression showed the expected lung cancer association with the presence of airflow obstruction (GOLD I–IV, odds ratio [OR], 2.09; 95% confidence interval [CI], 1.33–3.27). A second logistic regression showed lung cancer related to emphysema (OR, 3.56; 95% CI, 2.21–5.73). After additional adjustments for GOLD class, emphysema remained a strong and statistically significant factor related to lung cancer (OR, 3.14; 95% CI, 1.91–5.15).
Conclusions: Emphysema on CT scan and airflow obstruction on spirometry are related to lung cancer in a high-risk population. Emphysema is independently related to lung cancer. Both radiographic emphysema and airflow obstruction should be considered when assessing lung cancer risk.
doi:10.1164/rccm.200803-435OC
PMCID: PMC2556456  PMID: 18565949
emphysema; chronic obstructive pulmonary disease; lung cancer
5.  Prevalence of Airway Obstruction Assessed by Lung Function Questionnaire 
Mayo Clinic Proceedings  2011;86(5):375-381.
OBJECTIVE: To estimate the prevalence of unidentified chronic obstructive pulmonary disease (COPD) and determine the screening accuracy of the Lung Function Questionnaire (LFQ).
PATIENTS AND METHODS: Cigarette smokers who had a smoking history of 10 or more pack-years and were aged 30 years or older were recruited from 36 centers from February 18, 2009, to May 29, 2009. A total of 1575 patients completed a Web-based survey including the 5-item LFQ. Spirometry was performed on patients with an LFQ total score of 18 or less and on a subset scoring more than 18. The primary outcome was the proportion of patients at risk of airflow obstruction as measured by the LFQ (score, ≤18) in whom an airflow obstruction was confirmed by spirometry.
RESULTS: Of the patients who completed the LFQ, 849 (54%) had standardized spirometry data available. On the basis of LFQ and spirometry results, the estimated prevalence of possible COPD was 17.9% (95% confidence interval, 15.3%-20.6%). At a cut point of 18 or less, sensitivity, specificity, positive predictive value, and negative predictive value of the LFQ were 88%, 25%, 21%, and 90%, respectively. Approximately 1 in 5 patients (21%) aged 30 years or older and 1 in 4 (26%) aged 50 years or older scored 18 or less on the LFQ and had a ratio of forced expiratory volume in the first second of expiration to forced vital capacity less than 0.70.
CONCLUSION: On the basis of postbronchodilator spirometry results using weighted estimates, approximately 1 in 5 patients (21%) aged 30 years or older with a smoking history of 10 or more pack-years seen in a primary care setting is likely to have COPD. The LFQ could be a helpful COPD case-finding tool for clinicians to identify patients who need further evaluation.
Trial Registration: clinicaltrials.gov Identifier: NCT01013948
On the basis of postbronchodilator spirometry results using weighted estimates, approximately 1 in 5 patients aged 30 years or older with a smoking history of 10 or more pack-years seen in a primary care setting is likely to have chronic obstructive pulmonary disease.
doi:10.4065/mcp.2010.0787
PMCID: PMC3084639  PMID: 21531880
6.  Hypertension, Systemic Inflammation and Body Weight in Relation to Lung Function Impairment—An Epidemiological Study 
COPD  2009;6(4):250-255.
Recent reports on the simultaneous occurrence of systemic inflammation and airflow obstruction are usually based on a highly selective patient population, but their importance warrants further evaluation in the general population. The objectives were to study the interrelationship between airflow obstruction, smoking, hypertension, obesity and CRP as a marker of systemic inflammation in a randomly selected sample of the general Icelandic population (n = 939). This study comprised 758 randomly selected men and women 40 years and older living in Reykjavik, Iceland, and who were participating in the Burden of Obstructive Lung Disease (BOLD) study (81% response rate). In addition to the BOLD protocol, which included post-bronchodilator spirometry, they answered questions about general health and medication. Serum samples were taken for measurement of C-reactive protein (CRP). In the sample—245 individuals (33%) reported having hypertension. Subjects with hypertension were older, had a higher BMI and higher CRP levels. Subjects with hypertension had lower values of FEV1 than predicted (89.9 ± 18.5 vs. 94.5 ± 14.4%) (p < 0.001) and FVC (92.2 ± 15.1 vs. 95.3 ± 12.3%) (p = 0.002). These differences remained significant after adjusting for age, BMI, CRP and smoking. Hypertension and CRP levels above the median were both independently and additively associated with lower FEV1 and FVC. In addition a lower FVC% was also associated with a higher BMI (> 30 mg/m2). Use of betablocking antihypertensives was not related to lung function. Hypertension, BMI and systemic inflammation affect lung function independently of each other. All three variables have a negative effect on FVC, while hypertension and high CRP were independently associated with impaired FEV1.
PMCID: PMC3334274  PMID: 19811383
Airflow obstruction; hypertension; obesity; systemic inflammation; cytokines
7.  The relationship between COPD and lung cancer in African American patients 
Clinical lung cancer  2011;13(2):149-156.
Rationale
Airflow obstruction and/or emphysema have been associated with lung cancer risk, however this relationship and the joint occurrence of these conditions are not well studied in the African American population.
Objective
Describe the prevalence of airflow obstruction and/or emphysema in African Americans with lung cancer and evaluate their impact on the management and outcome of lung cancer.
Methods
Medical records were reviewed for 114 African Americans who had participated in population-based case-control studies of lung cancer and who sought medical care at the Karmanos Cancer Center in Detroit, Michigan. The medical records of these patients were reviewed for demographics, type and stage of lung cancer, spirometry, treatment and outcome. The chest CT scans around the time of the diagnosis of lung cancer were reviewed by a radiologist for evidence of emphysema. COPD was diagnosed when there were changes consistent with emphysema on CT scan and/or airflow obstruction by spirometry.
Results
There were no differences by sex for age at lung cancer diagnosis (p=0.78) and tumor histology (p=0.43). Men were more likely to present at a later stage of lung cancer diagnosis compared to women (p=0.04) and women were more likely to have surgery than men (p=0.03). Overall, 94% of men and 78% of women in this population had spirometry and/or CT evidence of COPD. Men were somewhat more likely to have COPD diagnosed by either CT or spirometry than women (p=0.06), but the GOLD Classification scores did not differ by gender among those with spirometry-diagnosed COPD (p=0.34). Seventy eight percent of individuals who did not report a previous diagnosis of COPD had clinical evidence of COPD, whereas 94% of individuals who reported a previous diagnosis of COPD also had clinical evidence of COPD (p=0.03). Among individuals who had both spirometry and CT data available, 29% had CT evidence of emphysema but normal spirometry. No differences in COPD diagnosis (p=0.82) or emphysema diagnosis (p=0.51) were noted by tumor histology. Stage at diagnosis also did not differ by COPD or emphysema diagnosis (p=0.30 and p=0.06, respectively), nor did treatment modality (p=0.54 and p=0.10, respectively). Lung cancer patients with COPD diagnosed either via spirometry or CT did not show an increased risk of death compared to lung cancer patients without COPD after adjusting for age at diagnosis, gender and stage (HR=1.31 95% CI: 0.68-2.53).
Conclusion
There is a high incidence of COPD, emphysema in particular, in a selected group of African American patients with lung cancer. A significant number of these patients were not aware that they had COPD. There was no significant difference in the outcome of lung cancer in relation to the presence or absence of COPD.
doi:10.1016/j.cllc.2011.09.006
PMCID: PMC3422020  PMID: 22129972
8.  Prevalence of airflow limitation in outpatients with cardiovascular diseases in Japan 
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.2147/COPD.S59962
PMCID: PMC4044996  PMID: 24920894
COPD; CVD; handheld spirometer; lung function; diagnosis
9.  COPD is frequent in conditions of comorbidity in patients treated with various diseases in a university hospital 
Background
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death and loss of disability-adjusted life-years. However, many COPD patients are not diagnosed because of underrecognition or underdiagnosis of this disease among many patients and physicians. One possible reason is underrecognition of spirometry. In this study, we examined the prevalence of airflow limitation and underlying disease in patients with airflow limitation.
Methodology
From April 2006 to March 2008, patients who had spirometry performed were examined. The original disease of patients, pulmonary function tests, smoking status, and respiratory symptoms were surveyed from their medical records.
Results
Of all patients who had spirometry performed, 15.8% showed airflow limitation (FEV1/FVC < 0.7). A variety of diseases were observed in patients with airflow limitation. Among all diseases, cardiovascular disease was the highest and gastrointestinal malignant disease had the second highest prevalence in patients with airflow limitation.
Conclusion
COPD might be frequent in conditions of comorbidity in patients treated for various diseases. Attention should be paid to the possibility of co-existence of COPD and the influence of COPD on these patients.
doi:10.2147/COPD.S12669
PMCID: PMC2962301  PMID: 21037959
airflow limitation; chronic obstructive pulmonary disease; comorbidity; spirometry; prevalence
10.  The Course of Persistent Airflow Limitation in Subjects with and without Asthma 
Respiratory medicine  2008;102(10):1473-1482.
Rationale
Most patients who develop persistent airflow limitation do so either as a manifestation of chronic obstructive pulmonary disease that is largely related to smoking or as a consequence of persistent asthma. We sought to compare the natural course of lung function associated with persistent airflow limitation in subjects with and without asthma from early to late adult life.
Methods
We studied 2552 participants aged 25 or more who had multiple questionnaire and lung function data from the long-term prospective population-based Tucson Epidemiological Study of Airway Obstructive Disease. Persistent airflow limitation was defined as FEV1/FVC ratio consistently < 70% in all completed surveys subsequent to the first survey with airflow limitation. Participants were divided into nine groups based on the combination of their physician-confirmed asthma status (never, onset ≤ 25 years, or onset > 25 years) and the presence of airflow limitation during the study follow-up (never, inconsistent, or persistent).
Results
Among subjects with an asthma onset ≤ 25 years, blood eosinophilia increased significantly the odds of developing persistent airflow limitation (adjOR: 3.7, 1.4–9.5), whereas cigarette smoking was the strongest risk factor for persistent airflow limitation among non-asthmatics and among subjects with asthma onset after age 25 years. Among subjects with persistent airflow limitation, the natural course of lung function differed between subjects with asthma onset ≤ 25 years and non-asthmatics, with the former having lower FEV1 levels at age 25 (predicted value for a 175-cm tall male of 3,400 versus 4,090 ml, respectively; p<0.001) and the latter having greater FEV1 loss between age 25 and 75 (1,590 versus 2,140 ml; p=0.003).
Conclusion
In subjects who have asthma onset before 25 years of age and persistent airflow limitation in adult life, the bulk of the FEV1 deficit is already established before age 25 years.
doi:10.1016/j.rmed.2008.04.011
PMCID: PMC2629140  PMID: 18684603
asthma; COPD; eosinophilia; airflow limitation
11.  Wood Smoke Exposure and Gene Promoter Methylation Are Associated with Increased Risk for COPD in Smokers 
Rationale: Wood smoke–associated chronic obstructive pulmonary disease (COPD) is common in women in developing countries but has not been adequately described in developed countries.
Objectives: Our objective was to determine whether wood smoke exposure was a risk factor for COPD in a population of smokers in the United States and whether aberrant gene promoter methylation in sputum may modify this association.
Methods: For this cross-sectional study, 1,827 subjects were drawn from the Lovelace Smokers' Cohort, a predominantly female cohort of smokers. Wood smoke exposure was self-reported. Postbronchodilator spirometry was obtained, and COPD outcomes studied included percent predicted FEV1, airflow obstruction, and chronic bronchitis. Effect modification of wood smoke exposure with current cigarette smoke, ethnicity, sex, and promoter methylation of lung cancer-related genes in sputum on COPD outcomes were separately explored. Multivariable logistic and poisson regression models were used for binary and rate-based outcomes, respectively.
Measurements and Main Results: Self-reported wood smoke exposure was independently associated with a lower percent predicted FEV1 (point estimate [± SE] −0.03 ± 0.01) and a higher prevalence of airflow obstruction and chronic bronchitis (odds ratio, 1.96; 95% confidence interval, 1.52–2.52 and 1.64 (95% confidence interval, 1.31–2.06, respectively). These associations were stronger among current cigarette smokers, non-Hispanic whites, and men. Wood smoke exposure interacted in a multiplicative manner with aberrant promoter methylation of the p16 or GATA4 genes on lower percent predicted FEV1.
Conclusions: These studies identify a novel link between wood smoke exposure and gene promoter methylation that synergistically increases the risk for reduced lung function in cigarette smokers.
doi:10.1164/rccm.201002-0222OC
PMCID: PMC3001253  PMID: 20595226
wood smoke; cigarette smokers; airflow obstruction; gene promoter methylation in sputum DNA
12.  Validity of a questionnaire-based diagnosis of chronic obstructive pulmonary disease in a general population-based study 
Background
The diagnosis of chronic obstructive pulmonary disease (COPD) is based on airflow obstruction. In epidemiological studies, spirometric data have often been lacking and researchers have had to rely almost solely on questionnaire answers. The aim of this study is to assess the diagnostic accuracy of questionnaire answers to detect COPD.
Methods
A sample of the Swedish general population without physician-diagnosed asthma was randomly selected and interviewed using a respiratory questionnaire. All eligible subjects aged 25–75 years (n = 3892) performed spirometry for detection of airflow obstruction using Global Initiative for Chronic Obstructive Lung Disease (GOLD) or American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria. Sensitivity, specificity, positive likelihood ratio (LR+), positive predictive values (PPVs), and negative predictive values (NPVs) were calculated to define diagnostic accuracy of questionnaire answers.
Results
The sensitivity of the question “Have you been diagnosed by a physician as having COPD or emphysema?” in detecting airflow obstruction was 5.7% using GOLD, and 9.8% using ATS/ERS, criteria; specificity was 99.7% for GOLD and 99.5% for ATS/ERS. Sensitivity, specificity, and PPV were higher for the question compared to self-reported symptoms of chronic bronchitis in identifying subjects with airflow obstruction.
Conclusions
The high specificity and good PPV suggest that the question “Have you been diagnosed by a physician as having COPD or emphysema?” is more likely to identify those who do not have airflow obstruction, whereas the low sensitivity of this question could underestimate the real burden of COPD in the general population.
doi:10.1186/1471-2466-14-49
PMCID: PMC3994476  PMID: 24650114
Airway obstruction; Spirometry; Sensitivity; Accuracy; ATS/ERS; GOLD
13.  Citric acid cough threshold and airway responsiveness in asthmatic patients and smokers with chronic airflow obstruction. 
Thorax  1991;46(9):638-642.
The relation between citric acid cough threshold and airway hyperresponsiveness was investigated in 11 non-smoking patients with allergic asthma (mean FEV1 94% predicted) and 25 non-atopic smokers with chronic airflow obstruction (mean FEV1 65% predicted). Cough threshold was determined on two occasions by administering doubling concentrations of citric acid. Seven of the 11 asthmatic subjects and 14 of 25 smokers with chronic airflow obstruction had a positive cough threshold on both test days. Cough threshold measurements were reproducible in both groups (standard deviation of duplicate measurements 1.2 doubling concentrations in asthma, 1.1 doubling concentrations in chronic airflow obstruction). Citric acid provocation did not cause bronchial obstruction in most patients, though four patients had a fall in FEV1 of more than 20% for a short time on one occasion only. No significant difference in cough threshold was found between the two patient groups despite differences in baseline FEV1 values. There was no significant correlation between cough threshold and the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) histamine in either group. Thus sensory nerves can be activated with a tussive agent in patients with asthma and chronic airflow obstruction without causing bronchial smooth muscle contraction.
PMCID: PMC463351  PMID: 1948792
14.  An international survey of chronic obstructive pulmonary disease in young adults according to GOLD stages 
Thorax  2004;59(2):120-125.
Background: The recently published GOLD guidelines provide a new system for staging chronic obstructive pulmonary disease (COPD) from mild (stage I) to very severe (stage IV) and introduce a stage 0 (chronic cough and phlegm without airflow obstruction) that includes subjects "at risk" of developing the disease.
Methods: In order to assess the prevalence of GOLD stages of COPD in high income countries and to evaluate their association with the known risk factors for airflow obstruction, data from the European Community Respiratory Health Survey on more than 18 000 young adults (20–44 years) were analysed.
Results: The overall prevalence was 11.8% (95% CI 11.3 to 12.3) for stage 0, 2.5% (95% CI 2.2 to 2.7) for stage I, and 1.1% (95% CI 1.0 to 1.3) for stages II–III. Moderate to heavy smoking (⩾15 pack years) was significantly associated with both stage 0 (relative risk ratio (RRR) = 4.15; 95% CI 3.55 to 4.84) and stages I+ (RRR = 4.09; 95% CI 3.17 to 5.26), while subjects with stages I+ COPD had a higher likelihood of giving up smoking (RRR = 1.39; 95% CI 1.04 to 1.86) than those with GOLD stage 0 (RRR = 1.05; 95% CI 0.86 to 1.27). Environmental tobacco smoke had the same degree of positive association in both groups. Respiratory infections in childhood and low socioeconomic class were significantly and homogeneously associated with both groups, whereas occupational exposure was significantly associated only with stage 0. All the GOLD stages showed a significantly higher percentage of healthcare resource users than healthy subjects (p<0.001), with no difference between stage 0 and COPD.
Conclusions: A considerable percentage of young adults already suffered from COPD. GOLD stage 0 was characterised by the presence of the same risk factors as COPD and by the same high demand for medical assistance.
doi:10.1136/thorax.2003.011163
PMCID: PMC1746950  PMID: 14760151
15.  Diagnosing and treating COPD: understanding the challenges and finding solutions 
Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction that is not fully reversible; symptoms include chronic cough, sputum production, and dyspnea with exertion. An estimated 50% of the 24 million adults in the USA who have COPD are thought to be misdiagnosed or undiagnosed. Factors contributing to this include a low awareness of COPD and the initial symptoms of the disease among the general population, acceptance of these symptoms as a consequence of aging or smoking, some symptomatic similarity to asthma, and failure of health care personnel to use spirometry for diagnosis. Increased familiarization with COPD diagnosis and treatment guidelines, and proactive identification of patients with increased risk of developing COPD through occupational, environmental, or lifestyle exposures, will assist in a timely, accurate diagnosis and effective treatment, which will consequently improve patient outcomes. This review addresses the issues surrounding the diagnosis and misdiagnosis of COPD, their consequences, and how COPD can be better managed within primary care, including consideration of COPD care in patient-centered medical home and chronic care models.
doi:10.2147/IJGM.S21387
PMCID: PMC3219759  PMID: 22114517
primary care; undiagnosed; misdiagnosed; chronic care model; patient-centered medical home
16.  Estimating the U.S. prevalence of chronic obstructive pulmonary disease using pre- and post-bronchodilator spirometry: the National Health and Nutrition Examination Survey (NHANES) 2007–2010 
Respiratory Research  2013;14(1):103.
Background
During 2007–2010, the National Health and Nutrition Examination Survey (NHANES) conducted a spirometry component which obtained pre-bronchodilator pulmonary lung function data on a nationally representative sample of US adults aged 6–79 years and post-bronchodilator pulmonary lung function data for the subset of adults with airflow limitation. The goals of this study were to 1) compute prevalence estimates of chronic obstructive pulmonary disease (COPD) using pre-bronchodilator and post-bronchodilator spirometry measurements and fixed ratio and lower limit of normal (LLN) diagnostic criteria and 2) examine the potential impact of nonresponse on the estimates.
Methods
This analysis was limited to those aged 40–79 years who were eligible for NHANES pre-bronchodilator spirometry (n=7,104). Examinees with likely airflow limitation were further eligible for post-bronchodilator testing (n=1,110). Persons were classified as having COPD based on FEV1/FVC < 70% (fixed ratio) or FEV1/FVC < lower limit of normal (LLN) based on person’s age, sex, height, and race/ethnicity. Those without spirometry but self-reporting both daytime supplemental oxygen therapy plus emphysema and/or current chronic bronchitis were also classified as having COPD. The final analytic samples for pre-bronchodilator and post-bronchodilator analyses were 77.1% (n=5,477) and 50.8% (n=564) of those eligible, respectively. To account for non-response, NHANES examination weights were adjusted to the eligible pre-bronchodilator and post-bronchodilator subpopulations.
Results
In 2007–2010, using the fixed ratio criterion and pre-bronchodilator test results, COPD prevalence was 20.9% (SE 1.1) among US adults aged 40–79 years. Applying the same criterion to post-bronchodilator test results, prevalence was 14.0% (SE 1.0). Using the LLN criterion and pre-bronchodilator test results, the COPD prevalence was 15.4% (SE 0.8), while applying the same criterion to post-bronchodilator test results, prevalence was 10.2% (SE 0.8).
Conclusions
The overall COPD prevalence among US adults aged 40–79 years varied from 10.2% to 20.9% based on whether pre- or post-bronchodilator values were used and which diagnostic criterion (fixed ratio or LLN) was applied. The overall prevalence decreased by approximately 33% when airflow limitation was based on post-bronchodilator as compared to pre-bronchodilator spirometry, regardless of which diagnostic criterion was used.
doi:10.1186/1465-9921-14-103
PMCID: PMC3854606  PMID: 24107140
Spirometry; Bronchodilator; COPD; Prevalence; NHANES
17.  Relationships among Smoking Habits, Airflow Limitations, and Metabolic Abnormalities in School Workers 
PLoS ONE  2013;8(11):e81145.
Background
Chronic obstructive pulmonary disease is caused mainly by habitual smoking and is common among elderly individuals. It involves not only airflow limitation but also metabolic disorders, leading to increased cardiovascular morbidity and mortality.
Objective
We evaluated relationships among smoking habits, airflow limitation, and metabolic abnormalities.
Methods
Between 2001 and 2008, 15,324 school workers (9700 males, 5624 females; age: ≥30 years) underwent medical checkups, including blood tests and spirometry. They also responded to a questionnaire on smoking habits and medical history.
Results
Airflow limitation was more prevalent in current smokers than in ex-smokers and never-smokers in men and women. The frequency of hypertriglyceridemia was higher in current smokers in all age groups, and those of low high-density-lipoprotein cholesterolemia and diabetes mellitus were higher in current smokers in age groups ≥ 40 s in men, but not in women. There were significant differences in the frequencies of metabolic abnormalities between subjects with airflow limitations and those without in women, but not in men. Smoking index was an independent factor associated with increased frequencies of hypertriglyceridemia (OR 1.015; 95% CI: 1.012–1.018; p<0.0001) and low high-density-lipoprotein cholesterolemia (1.013; 1.010–1.016; p<0.0001) in men. Length of smoking cessation was an independent factor associated with a decreased frequency of hypertriglyceridemia (0.984; 0.975–0.994; p = 0.007).
Conclusions
Habitual smoking causes high incidences of airflow limitation and metabolic abnormalities. Women, but not men, with airflow limitation had higher frequencies of metabolic abnormalities.
doi:10.1371/journal.pone.0081145
PMCID: PMC3843673  PMID: 24312268
18.  Development of the Lung Function Questionnaire (LFQ) to identify airflow obstruction 
Objective:
To describe the item-selection and item-reduction for the Lung Function Questionnaire (LFQ), being developed to help clinicians identify patients appropriate for diagnostic evaluation for chronic obstructive pulmonary disease (COPD) using spirometry.
Methods:
Item selection and reduction were based on information from 387 ≥40-year-old respondents to the third National Health and Nutrition Examination Survey who had self-reported chronic bronchitis. Item reduction involved stepwise logistic regression. The accuracy of the final subset of items for identifying individuals with airflow obstruction (forced expiratory volume in one second/forced vital capacity <0.70) versus those without it was assessed with receiver operating characteristic analysis. Content and face validity were assessed using focus groups of primary care physicians (n = 16) and interviews with COPD patients (n = 16).
Results:
The model with all five items (age; smoking history; the presence of wheeze, dyspnea, and phlegm) compared with models with combinations of fewer items had the highest classification accuracy (area under the curve [AUC] = 0.720) with sensitivity and specificity of 73.2% and 58.2%, respectively. The presence of three or more factors yielded the highest AUC, a result suggesting that three or more affirmative answers is the most appropriate criterion indicating presence of airflow obstruction.
Conclusions:
The five-item LFQ retained sufficient accuracy, sensitivity, and specificity in identifying individuals with COPD for further validation testing.
PMCID: PMC2846155  PMID: 20368906
spirometry; chronic obstructive pulmonary disease; respiratory disease; chronic bronchitis; diagnosis; screening
19.  Cigarette Smoking Is Associated with Subclinical Parenchymal Lung Disease 
Rationale: Cigarette smoking is a risk factor for diffuse parenchymal lung disease. Risk factors for subclinical parenchymal lung disease have not been described.
Objectives: To determine if cigarette smoking is associated with subclinical parenchymal lung disease, as measured by spirometric restriction and regions of high attenuation on computed tomography (CT) imaging.
Methods: We examined 2,563 adults without airflow obstruction or clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis, a population-based cohort sampled from six communities in the United States. Cumulative and current cigarette smoking were assessed by pack-years and urine cotinine, respectively. Spirometric restriction was defined as a forced vital capacity less than the lower limit of normal. High attenuation areas on the lung fields of cardiac CT scans were defined as regions having an attenuation between −600 and −250 Hounsfield units, reflecting ground-glass and reticular abnormalities. Generalized additive models were used to adjust for age, gender, race/ethnicity, smoking status, anthropometrics, center, and CT scan parameters.
Measurements and Main Results: The prevalence of spirometric restriction was 10.0% (95% confidence interval [CI], 8.9–11.2%) and increased relatively by 8% (95% CI, 3–12%) for each 10 cigarette pack-years in multivariate analysis. The median volume of high attenuation areas was 119 cm3 (interquartile range, 100–143 cm3). The volume of high attenuation areas increased by 1.6 cm3 (95% CI, 0.9–2.4 cm3) for each 10 cigarette pack-years in multivariate analysis.
Conclusions: Smoking may cause subclinical parenchymal lung disease detectable by spirometry and CT imaging, even among a generally healthy cohort.
doi:10.1164/rccm.200812-1966OC
PMCID: PMC2742759  PMID: 19542480
cigarette smoking; computed tomography; interstitial lung disease; restrictive lung disease; spirometry
20.  The Changes of Pulmonary Function in COPD During Four-Year Period 
Materia Socio-Medica  2013;25(2):88-92.
Conflict of interest: none declared.
Introduction
COPD (chronic obstructive pulmonary disease) is characterized by airflow limitation that is not fully reversible. OBJECTIVE: to show the changes of pulmonary function in COPD during the 4 -year evolution of illness.
Material and Methods
The research was done on patients suffering from COPD treated at the Clinic “Podhrastovi” during 2006 and 2007. The tested parameters were examined from the date of receiving patient with COPD to hospital treatment in 2006 and 2007 and then followed prospectively until 2010 or 2011 (the follow-up period was 4 years). There were total 199 treated patients who were chosen at random and regularly attended the control examinations. The study was conducted on adult patients of both sexes, different age group. In each patient the duration of illness was recorded so is sex, age, data of smoking habits, information about the regularity of taking bronchodilator therapy during remissions of disease, about the treatment of disease exacerbations, results of pulmonary functional tests as follows: FVC (forced vital capacity), FEV1 (forced expiratory volume in one second) and bronchodilator reversibility testing. All these parameters were measured at the beginning and at the end of each hospital treatment on the apparatuses of Clinic “Podhrastovi”. We took in elaboration those data obtained in the beginning of the first hospitalization and at the end of the last hospitalization or at the last control in outpatient department when patient was in stable state. Patients were divided into three groups according to the number of exacerbations per year.
Results
airflow limitation in COPD is progressive; both FVC and FEV1 shows the statistically significant decrease during follow-up period of 4 years (p values / for both parameters/ =0.05) . But in patients regularly treated in phases of remission and exacerbations of illness the course of illness is slower. The fall of FVC and FEV1 is statistically significantly smaller in those received regular treatment in phases of remissions and exacerbations of illness (p values / for both parameters/ =0.01). The number of patients responding properly to bronchodilators decreased statistically significantly in patients with COPD during follow-up period (p=0.05).
Conclusion
COPD is characterized with airflow limitation which is progressive in the course of illness, but that course may be made slower using appropriate treatment during remission and exacerbations of diseases.
doi:10.5455/msm.2013.25.88-92
PMCID: PMC3769154  PMID: 24082829
COPD; FVC; FEV1; airflow limitation; treatment; bronchodilator response
21.  Airways obstruction in rheumatoid arthritis. 
Annals of the Rheumatic Diseases  1979;38(3):222-225.
Owing to the report of an association between rheumatoid arthritis (RA) and obliterative bronchiolitis we have determined the prevalence of airflow obstruction in unselected patients with RA and normal chest radiographs. Spirometry was performed on 100 patients with rheumatoid arthritis and 84 control subjects matched for age, sex, and smoking habits. Patients with rheumatoid arthritis had significantly lower values for FEV1, FVC, FEV1/FVC, and MMEFR when compared with the controls: 39 patients had abnormal spirometry, and at least 32 showed airways obstruction. The prevalence of airflow obstruction is remarkably high, and we suggest that airway disease may be the commonest form of lung involvement in rheumatoid arthritis.
PMCID: PMC1000439  PMID: 485577
22.  Bronchial responsiveness to methacholine in chronic bronchitis: relationship to airflow obstruction and cold air responsiveness. 
Thorax  1984;39(12):912-918.
The response to inhaled methacholine is increased in patients with chronic airflow obstruction, but it is not known whether this is due to true hyperresponsiveness or is a result of the airflow obstruction. In asthmatics the response to methacholine correlates with the bronchoconstriction produced by hyperventilation of cold dry air. We studied 27 patients with a history of smoking and chronic bronchitis with a range of severity of airflow obstruction. Bronchial responses to methacholine (expressed as the provocation concentration causing a fall in FEV1 of 20%-PC20) and isocapnic hyperventilation of cold dry air were measured. In 19 patients the PC20 was less than 8 mg/ml (that is, in the asthmatic range) but only three developed bronchoconstriction in response to hyperventilation. There was a linear correlation between the log PC20 and the FEV1 (r = 0.86, p less than 0.001). The results suggest that in patients with chronic airflow obstruction the response to methacholine is determined by the degree of airflow obstruction, and cannot be used in the diagnosis of asthma in the absence of additional information.
PMCID: PMC459952  PMID: 6393416
23.  Chronic airflow obstruction and markers of systemic inflammation: Results from the BOLD study in Iceland 
Respiratory medicine  2009;103(10):1548-1553.
Summary
Background
Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible chronic airflow obstruction and by an accelerated decline in lung function. Elevated circulating levels of C-reactive protein (CRP) and interleukin-6 (IL-6), both markers of systemic inflammation, have been found in COPD. Their possible associations with chronic airflow obstruction have mostly been evaluated in highly selected patient samples. Our objective was to evaluate the association between postbronchodilator lung function CRP and IL-6 in a randomly selected sample of the Icelandic population, 40 years and older, while adjusting for gender, age, smoking, and body weight.
Methods
Serum CRP and IL-6 values were measured among participants in the Burden of Obstructive Lung Disease (BOLD) study.
Results
Of the 938 subjects invited a total of 403 men and 355 women participated (response rate 81%) in the study. Their mean age (±SD) was 57.7 (±12.7) years. Both CRP and IL-6 were independently related to lower FEV1 and FVC values. Individuals in the highest quartiles of CRP and IL-6 had a 7.5% and 3.9%, respectively, lower FEV1% than predicted after adjustment for smoking, age, and body weight. High CRP levels were more strongly related to lower FEV1 levels in men (−11.4%) than in women ( −0.4%).
Conclusions
In a random population-based sample both CRP and IL-6 were significantly related to lower spirometric values. The association with CRP was stronger in men than in women. This finding underscores the possible importance of systemic inflammation in irreversible airflow limitation.
doi:10.1016/j.rmed.2009.04.005
PMCID: PMC3334275  PMID: 19427181
Airflow obstruction; Systemic inflammation; Cytokines; C-reactive protein; IL-6
24.  Epidemiology of the Origins of Airflow Limitation in Asthma 
There is now conclusive evidence that, as a group, subjects with asthma have lower levels of lung function as compared with their peers and that a significant proportion of subjects with persistent asthma are at risk of developing non–fully reversible airflow limitation, the clinical hallmark of chronic obstructive pulmonary disease. Although at the population level the most conspicuous form of airflow limitation in asthma seems to be that of subjects who wheeze during the first years of life and whose symptoms persist into adult life, asthma-related lung deficits can be related to both acquired deficits in growth of lung function in childhood and steeper decline of lung function in adult life. These trajectories of lung function are likely to differ across subgroups of individuals with asthma, suggesting that different windows of opportunity may exist to modify the natural course of the disease before irreversible deficits are established. These observations indicate the importance of identifying biomarkers that can be used to target children and adults with asthma at increased risk for airflow limitation and determining whether pharmacological interventions can protect these patients from the development of chronic obstructive pulmonary disease.
doi:10.1513/pats.200908-085DP
PMCID: PMC2797072  PMID: 20008881
asthma; chronic obstructive pulmonary disease; lung function; airflow limitation; FEV1
25.  The Association of Pipe and Cigar Use with Cotinine Levels, Lung Function and Airflow Obstruction: a Cross-sectional Study 
Annals of internal medicine  2010;152(4):201-210.
Background
Cigarette smoking is the major cause of chronic obstructive pulmonary disease but studies on the contribution of other smoking techniques are sparse.
Objective
We hypothesized that pipe and cigar smoking was associated with elevated cotinine levels, decrements in lung function and increased odds of airflow obstruction.
Design
Cross-sectional study.
Setting
Population-based sample from six US communities.
Participants
The Multi-Ethnic Study of Atherosclerosis (MESA) recruited men and women ages 45-84 years without clinical cardiovascular disease.
Measurements
The MESA Lung Study measured spirometry following American Thoracic Society guidelines and urinary cotinine levels by immunoassay. Pipe-years and cigar-years were calculated as years from self-reported age of starting to quitting (or to current age among current users) × pipefuls or cigars per day.
Results
Of 3,528 participants, 8% reported pipe smoking (median 15 pipe-years), 11% reported cigar smoking (median 6 cigar-years), and 52% reported cigarette smoking (median 18 pack-years). Self-reported current pipe and cigar smokers had elevated urinary cotinine levels compared to never smokers. Pipe-years were associated with decrements in the forced expiratory volume in one second (FEV1) and cigar-years were associated with decrements in the FEV1 and the ratio of the FEV1 to the forced vital capacity. Participants who smoked pipes or cigars had an increased odds of airflow obstruction whether they had also smoked cigarettes (Odds ratio 3.43; 95% CI: 1.75, 6.71; P<0.001) or had never smoked cigarettes (Odds ratio 2.31; 95% CI: 1.04, 5.11; P=0.039) compared to participants with no smoking history.
Limitations
Cross-sectional design.
Conclusions
Pipe and cigar smoking increased urinary cotinine levels and was associated with decrements in lung function and increased odds of airflow obstruction, even among participants who never smoked cigarettes.
doi:10.1059/0003-4819-152-4-201002160-00004
PMCID: PMC2906916  PMID: 20157134

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