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1.  Systemic inflammation and decline in lung function in a general population: a prospective study 
Thorax  2007;62(6):515-520.
Background
An increase in levels of C‐reactive protein (CRP), a marker of systemic inflammation, is associated with reduced forced expiratory volume in 1 s (FEV1), supporting the hypothesis that the pathophysiology of chronic obstructive pulmonary disease has a systemic inflammatory component. However, few large studies have assessed the relationship between systemic inflammation as measured by CRP and decline in lung function prospectively in a randomly selected population.
Methods
In 1991, data were collected on FEV1 and forced vital capacity (FVC) and a blood sample was taken from 2442 randomly selected adults in a community‐based cohort. In 2000 these measures were repeated in 1301 individuals. The level of serum CRP was analysed in these samples from 1991 and 2000.
Results
In cross‐sectional analyses of data from 1991 and 2000, serum CRP levels were inversely related to FEV1 and FVC. After adjustment for smoking and other confounders, the difference in FEV1 was reduced by −9 ml (95% CI –13 to –5) and –7 ml (95% CI –13 to –2) for each mg/l increment in serum CRP in 1991 and 2000, respectively. There was no significant association between baseline serum CRP levels and decline in FEV1 and FVC over 9 years.
Conclusions
Although serum CRP levels are inversely associated with lung function in cross‐sectional studies, there was no effect of a marker of systemic inflammation on decline in lung function over 9 years.
doi:10.1136/thx.2006.066969
PMCID: PMC2117221  PMID: 17251312
2.  Association of bronchial hyperresponsiveness and lung function with C-reactive protein (CRP): a population based study 
Thorax  2004;59(10):892-896.
Background: C-reactive protein (CRP), a marker of systemic inflammation, is a powerful predictor of adverse cardiovascular events. Respiratory impairment is also associated with cardiovascular risk. Although some studies have found an inverse relationship between lung function and markers of systemic inflammation, only one study has reported a relationship between lung function and CRP levels. In contrast, little is known about the relationship between bronchial hyperresponsiveness (BHR) and systemic inflammation. The association between lung function and CRP and between BHR and CRP has been investigated.
Methods: As part of the European Community Respiratory Health Survey follow up study serum CRP levels, forced expiratory volume in 1 second (FEV1), and BHR to methacholine (⩾20% decrease in FEV1 to <4 mg methacholine) were measured in 259 adults aged 28–56 years free of cardiovascular disease or respiratory infection.
Results: Mean (SD) FEV1 (adjusted for age, sex, height, and smoking status) was lower in subjects with a high CRP level (high tertile) (3.29 (0.44) l/s v 3.50 (0.44) l/s; p<0.001) and BHR was more frequent (41.9% v 24.9%; p = 0.005) than in subjects with lower CRP levels (low+middle tertiles). Similar results were obtained when the potential confounding factors were taken into account. Similar patterns of results were found in non-smokers and in non-asthmatic subjects.
Conclusions: Increased CRP levels are strongly and independently associated with respiratory impairment and more frequent BHR. These results suggest that both respiratory impairment and BHR are associated with a systemic inflammatory process.
doi:10.1136/thx.2003.015768
PMCID: PMC1746828  PMID: 15454657
3.  Systemic Inflammation in Young Adults Is Associated with Abnormal Lung Function in Middle Age 
PLoS ONE  2010;5(7):e11431.
Background
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.
Methodology/Principal Findings
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).
Conclusion/Significance
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.
Trial Registration
ClinicalTrials.gov NCT00005130
doi:10.1371/journal.pone.0011431
PMCID: PMC2896391  PMID: 20625390
4.  Systemic Inflammation and Reduced Pulmonary Function in Chronic Spinal Cord Injury 
Objective
To evaluate the relationship between systemic inflammation and pulmonary function in persons with chronic spinal cord injury (SCI).
Design
Cross-sectional study.
Setting
Veterans Affairs Medical Center.
Participants
Fifty-nine men with chronic SCI participating in a prior epidemiologic study.
Methods
Standardized assessment of pulmonary function and measurement of plasma C-reactive protein (CRP) and interleukin-6 (IL-6).
Main Outcome Measurements
Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC).
Results
Persons with the highest values of IL-6 had the lowest %-predicted FEV1 and FVC. There was a significant inverse linear trend between quartile of IL-6 and %-predicted FEV1 (P < .001) and FVC (P < .006), unadjusted and adjusted for SCI level and completeness of injury, obstructive lung disease history, smoking, and body mass index (P = .010-.039). Although not as strong as for IL-6, there also were similar trends for %-predicted FEV1 and FVC with CRP.
Conclusions
In chronic SCI, higher levels of IL-6 and CRP were associated with a lower FEV1 and FVC, independent of level and completeness of injury. These results suggest that the reduction of pulmonary function after SCI is related not only to neuromuscular impairment but also to factors that promote systemic inflammation.
doi:10.1016/j.pmrj.2011.02.003
PMCID: PMC3141080  PMID: 21570031
5.  Inflammatory Markers and Longitudinal Lung Function Decline in the Elderly 
American Journal of Epidemiology  2008;168(6):602-610.
Longitudinal studies examining associations of the inflammatory markers fibrinogen and C-reactive protein (CRP) with lung function decline are sparse. The authors examined whether elevated fibrinogen and CRP levels were associated with greater longitudinal lung function decline in the elderly. The Cardiovascular Health Study measured fibrinogen and CRP in 5,790 Whites and African Americans from four US communities aged 65 years or older in 1989–1990 or 1992–1993. Spirometry was performed in 1989–1990 and 4, 7, and 16 years later. Fibrinogen and CRP were inversely associated with lung function at baseline after adjustment for multiple potential confounders. In mixed models, the rate of decline in forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio with increasing age was faster among those with higher baseline fibrinogen (−0.032%/year per standard deviation higher fibrinogen (95% confidence interval: −0.057, −0.0074)) but not among those with higher CRP (−0.0037%/year per standard deviation higher CRP (95% confidence interval: −0.013, 0.0056)). Longitudinal analyses for FEV1 and FVC yielded results in the direction opposite of that hypothesized, possibly because of the high mortality rate and strong inverse association of FEV1 and FVC but not FEV1/FVC with mortality. An alternative approach to missing data yielded similar results. In conclusion, higher levels of fibrinogen, but not CRP, independently predicted greater FEV1/FVC decline in the elderly.
doi:10.1093/aje/kwn174
PMCID: PMC2727196  PMID: 18687665
aged; biological markers; C-reactive protein; fibrinogen; forced expiratory volume; inflammation; spirometry; vital capacity
6.  Respiratory morbidity 10 years after the Union Carbide gas leak at Bhopal: a cross sectional survey. The International Medical Commission on Bhopal. 
BMJ : British Medical Journal  1997;314(7077):338-342.
OBJECTIVE: To examine the role of exposure to the 1984 Bhopal gas leak in the development of persistent obstructive airways disease. DESIGN: Cross sectional survey. SETTING: Bhopal, India. SUBJECTS: Random sample of 454 adults stratified by distance of residence from the Union Carbide plant. MAIN OUTCOME MEASURES: Self reported respiratory symptoms; indices of lung function measured by simple spirometry and adjusted for age, sex, and height according to Indian derived regression equations. RESULTS: Respiratory symptoms were significantly more common and lung function (percentage predicted forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), and FEV1/FVC ratio) was reduced among those reporting exposure to the gas leak. The frequency of symptoms fell as exposure decreased (as estimated by distance lived from the plant), and lung function measurements displayed similar trends. These findings were not wholly accounted for by confounding by smoking or literacy, a measure of socioeconomic status. Lung function measurements were consistently lower in those reporting symptoms. CONCLUSION: Our results suggest that persistent small airways obstruction among survivors of the 1984 disaster may be attributed to gas exposure.
PMCID: PMC2125830  PMID: 9040323
7.  Lung Function and Risk for Heart Failure Among Older Adults 
The American journal of medicine  2011;124(4):334-341.
Background
The impact of abnormal spirometric findings on risk for incident heart failure among older adults without clinically apparent lung disease is not well elucidated.
Methods
We evaluated the association of baseline lung function with incident heart failure, defined as first hospitalization for heart failure, in 2125 participants of the community-based Health, Aging, and Body Composition Study (age, 73.6±2.9 years; 50.5% men; 62.3% white; 37.7% black) without prevalent lung disease or heart failure. Abnormal lung function was defined either as forced vital capacity (FVC) or forced expiratory volume in 1st second (FEV1) to FVC ratio below lower limit of normal. Percent predicted FVC and FEV1 were also assessed as continuous variables.
Results
During follow-up (median, 9.4years), heart failure developed in 68 of 350 (19.4%) participants with abnormal baseline lung function, as compared to 172 of 1775 (9.7%) participants with normal lung function (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.74-3.07; P<.001). This increased risk persisted after adjusting for previously identified heart failure risk factors in the Health ABC Study, body mass index, incident coronary heart disease, and inflammatory markers (HR, 1.83; 95% CI, 1.33-2.50; P<.001). Percent predicted (%) FVC and FEV1 had a linear association with heart failure risk (HR, 1.21; 95%CI, 1.11-1.32 and 1.18; 95%CI, 1.10-1.26, per 10% lower %FVC and %FEV1, respectively; both P<.001 in fully adjusted models). Findings were consistent in sex and race subgroups, and for heart failure with preserved or reduced ejection fraction.
Conclusions
Abnormal spirometric findings in older adults without clinical lung disease are associated with increased heart failure risk.
doi:10.1016/j.amjmed.2010.12.006
PMCID: PMC3073738  PMID: 21435424
Elderly; Epidemiology; Heart Failure; Pulmonary Function Test
8.  Evaluation of asymptomatic subjects with low forced expiratory ratios (FEV1/VC). 
Thorax  1994;49(6):554-556.
BACKGROUND--Heightened bronchial hyperreactivity is frequently associated with airflow limitation, atopy, or cigarette smoking. The purpose of this study was to evaluate healthy subjects with significantly low values of forced expiratory volume in one second/vital capacity % (FEV1/VC%) by measuring their airway response to exercise and methacholine challenge, compared with a control group with normal spirometric values. METHODS--Eighty four healthy subjects with significantly low flow rates (group A, FEV1/VC% < 2 SD% predicted) were evaluated and compared with 37 subjects with normal flow rates (group B). Static lung volumes, spirometric tests, exercise, and methacholine challenges were performed. RESULTS--Lung volumes were normal for both groups. Mean FEV1/VC% was 69% for group A and 82% for the control group. Salbutamol improved baseline FEV1 in eight subjects in group A (mean 15%), while methacholine induced a drop in FEV1 in 12 subjects. The dose-response curve to methacholine reached a plateau in all the responders. None of the subjects in the control group improved their baseline FEV1/VC% to salbutamol, but three showed bronchial hyperreactivity similar to those in group A. CONCLUSIONS--Bronchial hyperreactivity does not occur more often in asymptomatic subjects with mildly low FEV1/VC% so these subjects do not require special investigations for airway disease.
PMCID: PMC474943  PMID: 8016792
9.  Effects of Smoking Cessation on Airflow Obstruction and Quality of Life in Asthmatic Smokers 
Purpose
Smoking elicits airway inflammation and airflow obstruction in patients with asthma, even after smoking cessation. The aim of this study was to examine the effects of smoking cessation on lung function and quality of life (QOL) in asthmatic patients.
Methods
Thirty-two patients with asthma who were active smokers were recruited. After education on the effects of smoking on asthma, 22 patients continued to smoke, and 10 quit smoking. All patients were treated with inhaled fluticasone propionate (1 mg/day) for 3 months. We compared forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow between 25 and 75% FVC (FEF25-75%), and scores on a QOL questionnaire at baseline, 1, 2, and 3 months.
Results
Quitters showed a greater percent change in FEV1 (19.1±6.3 vs. 7.9±2.4%, P=0.024) and FEV1/FVC (6.5±4.14 vs. 3.5±1.5%, P=0.05) than smokers. Both quitters and smokers showed improved QOL scores after 1, 2, and 3 months of fluticasone treatment.
Conclusions
Patients with asthma who quit smoking showed less airway obstruction, suggesting that smoking cessation is crucial in the management of asthma.
doi:10.4168/aair.2010.2.4.254
PMCID: PMC2946703  PMID: 20885910
Smoking; asthma; lung function; quality of life
10.  Abnormal lung function associated with asbestos disease of the pleura, the lung, and both: a comparative analysis. 
Thorax  1991;46(1):33-38.
The impairment of lung function associated with different types of asbestos related disease was examined in 1298 men. The 310 men with circumscribed pleural lesions (plaques) or diffuse pleural thickening without asbestosis were compared with 596 men with asbestosis only and with 322 men with pleural abnormalities and asbestosis, as classified from chest radiographs by ILO pneumoconiosis criteria. Spirometric indices and total lung capacity (TLC; determined by planimetry) were measured and expressed as percentages of predicted values. Non-smoking men with pleural disease only had reduced values of mid and terminal expiratory flows (80.6 and 69.9% predicted) and a reduced FEV1 (89% predicted) with a forced vital capacity (FVC) of 94% predicted. TLC was 104% predicted. Thus they had airways obstruction with-out restriction. Non-smoking men with pulmonary asbestosis (ILO profusion of opacities mostly 1/0 and 1/1) had pulmonary function similar to that of men with pleural disease. FEV1 and FVC and flow rates at other lung volumes were lower in smokers with asbestosis (after adjustment for duration of smoking) than in the non-smokers with asbestosis. Airflow limitation was worse in the men with both pleural abnormalities and pulmonary asbestosis with lower values for mid expiratory flow, FEV1 and FVC (but not TLC) than those with either abnormality alone, in both non-smokers and current smokers. Men with diffuse pleural thickening that included the costophrenic angles had more airways obstruction and air trapping and lower FVC values than those with circumscribed pleural disease.
PMCID: PMC1020911  PMID: 1871694
11.  Environmental tobacco smoke exposure and pulmonary function among adults in NHANES III: impact on the general population and adults with current asthma. 
Environmental Health Perspectives  2002;110(8):765-770.
The impact of environmental tobacco smoke (ETS) exposure on adult pulmonary function has not been clearly determined. Because adults with asthma have chronic airway inflammation, they may be a particularly susceptible group. Using data from the Third National Health and Nutrition Examination Survey (NHANES III), I examined the cross-sectional relationship between serum cotinine, a biomarker of ETS exposure, and pulmonary function among 10,581 adult nonsmokers and 440 nonsmoking adults with asthma whose cotinine and spirometry data were available. I generated residuals, which are observed minus predicted values (based on Crapo equations), for forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio to adjust for age, sex, and height. In addition, I used multivariate linear regression to control for sociodemographic characteristics and previous smoking history. Most adults with and without asthma had detectable serum cotinine levels, indicating recent ETS exposure (85.7% and 83.4%, respectively). Among nonsmoking male participants, I found no evidence that ETS exposure was related to decreased pulmonary function. In the nonsmoking female stratum, the highest cotinine tertile was associated with a lower FEV1 [-100 mL; 95% confidence interval (CI), -143 to -56 mL], FVC (-119 mL; 95% CI, -168 to -69 mL), and FEV1/FVC ratio (-1.77%; 95% CI, -2.18% to -1.36%). Among women with asthma, the highest cotinine tertile was also associated with decreased FEV1 (-261 mL; 95% CI, -492 to -30 mL), FVC (-291 mL; 95% CI, -601 to 20 mL), and FEV1/FVC ratio (-1.6%; 95% CI, -3.3% to 0.19%). In conclusion, ETS exposure is associated with decreased pulmonary function in adult females, especially those with asthma. This analysis should provide further impetus for public policies that promote smoke-free environments.
PMCID: PMC1240946  PMID: 12153756
12.  Effects of asbestos and smoking on the levels and rates of change of lung function in a crocidolite exposed cohort in Western Australia 
Thorax  2004;59(12):1052-1056.
Methods: The effects of crocidolite exposure and smoking history on levels and rates of change of lung function were evaluated using a linear mixed model. Lung function was measured as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC.
Results: Cumulative doses of asbestos and the presence of radiographic asbestosis were associated with lower levels of FEV1 and FVC and a steeper decline during the period of observation. Subjects exposed to asbestos at a younger age had lower levels of FEV1 and FVC. Current smokers had lower levels and a steeper decline in lung function than never smokers. No significant interactions between crocidolite exposure and smoking on the levels or rates of change of lung function were found.
Conclusions: The deleterious effects of crocidolite exposure on lung function persist in this population, despite asbestos exposure having ceased more than 30 years ago. No significant interactions were found in this population between asbestos and smoking at the first visit or longitudinally.
doi:10.1136/thx.2004.022806
PMCID: PMC1746913  PMID: 15563704
13.  A mathematical reason for FEV1/FVC dependence on age 
Respiratory Research  2012;13(1):57.
Background
Recent studies have showed that FEV1/FVC describing correspondence between the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) depends significantly on age. However, the nature of this dependence is uncertain. The study aim is to analyze mathematically the relationship between FEV1 and FVC to find a cause of the FEV1/FVC dependence on age in healthy subjects.
Methods
The relationship was examined for 1,120 males and 1,625 females – Polish (Caucasian) population, healthy, never-smoking, aged 18 – 85 years, who performed a technically adequate spirometry maneuver. Lung functions were measured using the LungTest1000 (MES, Poland) with maximal effort according to the ATS/ERS guidelines.
Results
A very strong, age-independent linear relationship between FEV1 and FVC was found in healthy individuals (the correlation coefficient r = 0.96). It can be described with the equation FEV1 = A x FVC + C, where A = 0.84 and C = −0.23 (−0.36) for females (males). As C is different from zero, FEV1/FVC depends on FVC because FEV1/FVC = A + C/FVC, in average. And thus, since FVC is significantly age-dependent, FEV1/FVC has to be also age-dependent because of the term C/FVC. In particular, the smaller the FVC value because of advanced age, the more significant the fall of FEV1/FVC.
Conclusions
FEV1/FVC dependence on age in healthy individuals is of mathematical rather than biological nature. Due to the strong correlation between FEV1 and FVC in healthy subjects, the difference between patient’s FEV1 and the FEV1 value expected for patient’s FVC seems to be a more natural, age-independent description of the correspondence between patient’s FEV1 and FVC.
doi:10.1186/1465-9921-13-57
PMCID: PMC3461438  PMID: 22762777
Age-dependence; Forced expiratory maneuver; Lung function tests; Obstructive lung disease; Spirometry
14.  Dietary fiber, lung function, and chronic obstructive pulmonary disease in the Atherosclerosis Risk in Communities (ARIC) Study 
American journal of epidemiology  2007;167(5):570-578.
Recent data suggest beneficial effects of fiber intake on chronic respiratory symptoms in adults that are independent of antioxidant vitamin intake, but little is known about fiber consumption in relation to lung function and chronic obstructive pulmonary disease (COPD). The authors investigated the association of fiber intake with lung function and COPD in 11,897 men and women from the Atherosclerosis Risk in Communities (ARIC) study. After controlling for potential confounders, positive associations between lung function and fiber intake from all sources as well as from cereal or fruit alone were found. Participants in the highest quintile of total fiber intake had 60.2 ml higher forced expiratory volume in 1 second (FEV1) (p for trend<0.001), 55.2 ml higher forced vital capacity (FVC) (p=0.001), 0.4% higher FEV1/FVC ratio (p=0.040), 1.8% higher percent predicted FEV1 (p<0.001), and 1.4% higher percent predicted FVC (p=0.001), compared with those in the lowest quintile. The adjusted odds ratios of COPD for the highest versus lowest quintiles of intake were 0.85 (p=0.044) for total fiber, 0.83 (p=0.021) for cereal fiber, and 0.72 (p=0.005) for fruit fiber. This study provides the first evidence that dietary fiber is independently associated with better lung function and reduced prevalence of COPD.
doi:10.1093/aje/kwm343
PMCID: PMC2377022  PMID: 18063592
COPD; FEV1; FVC; fiber; pulmonary function
15.  Lung Function and Risk of Type 2 Diabetes and Fatal and Nonfatal Major Coronary Heart Disease Events: Possible Associations With Inflammation 
Diabetes Care  2010;33(9):1990-1996.
OBJECTIVE
We prospectively examined the relationship between lung function and risk of type-2 diabetes and fatal and nonfatal coronary heart disease (CHD) events and investigated the hypothesis that inflammation may underlie these associations.
RESEARCH DESIGN AND METHODS
A prospective study of 4,434 men aged 40–59 years with no history of cardiovascular disease (CHD or stroke) or diabetes drawn from general practices in 24 British towns and followed up for 20 years.
RESULTS
There were 680 major CHD events (276 fatal, 404 nonfatal) and 256 incident type 2 diabetes during the 20 years follow-up. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) but not FEV1-to-FVC ratio were significantly and inversely associated with incident type 2 diabetes and fatal CHD events (not nonfatal events) after adjustment for age, potential confounders, and metabolic risk factors. The adjusted relative risk (RR) for type 2 diabetes (Quartile 1 vs. Quartile 4) were 1.59 (1.07–2.56) and 1.74 (1.16–2.61) for FVC and FEV1, respectively (P = 0.03 and P = 0.04 for trend). The corresponding RR for fatal CHD were 1.48 (1.00–2.21) and 1.81 (1.19–2.76) (P = 0.002 and P = 0.0003 for trend). Lung function was significantly and inversely associated with C-reactive protein and interleukin-6; the inverse associations with type 2 diabetes for FVC and FEV1 were attenuated after further adjustment for these factors (P = 0.14 and P = 0.11 for trend) but remained significant for fatal CHD (P = 0.03 and P = 0.01, respectively).
CONCLUSIONS
Restrictive rather than obstructive impairment of lung function is associated with incident type 2 diabetes (and fatal CHD) with both associations partially explained by traditional and metabolic risk factors and inflammation.
doi:10.2337/dc10-0324
PMCID: PMC2928349  PMID: 20519659
16.  Traffic exposure and lung function in adults: the Atherosclerosis Risk in Communities study 
Thorax  2007;62(10):873-879.
Background
Traffic exposure is a major contributor to ambient air pollution for people living close to busy roads. The relationship between traffic exposure and lung function remains inconclusive in adults.
Methods
We conducted a cross-sectional study to investigate the association between traffic exposure and lung function in the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort of 15,792 middle-aged men and women. Traffic density and distance to major roads were used as measures of traffic exposure.
Results
After controlling for potential confounders including demographic factors, personal and neighborhood level socioeconomic characteristics, cigarette smoking, and background air pollution, higher traffic density was significantly associated with lower forced expiratory volume at 1s (FEV1) and forced vital capacity (FVC) in females. Relative to the lowest quartile of traffic density, the adjusted differences across increasing quartiles were 5.1, −15.4 and −21.5ml for FEV1 (p value of linear trend across the quartiles =0.041), and 1.2, −23.4 and −34.8ml for FVC (p trend =0.010). Using distance from major roads as a simpler index of traffic related air pollution exposure, the FEV1 was −15.7ml (95%CI −34.4ml, 2.9ml) lower and the FVC was −24.2ml (95%CI −46.2ml, −2.3ml) lower for women living within 150 meters compared to subjects living further away. We did not find a significant effect of traffic density or distance to major roads on lung function among men. The FEV1/FVC ratio was not significantly associated with traffic exposure in either gender.
Conclusions
This is the largest published study of traffic exposure and pulmonary function in adults to date. These results add to growing evidence that chronic exposure to traffic-related air pollution may adversely affect respiratory health.
doi:10.1136/thx.2006.073015
PMCID: PMC2094260  PMID: 17442705
air pollution; traffic; pulmonary function; FEV1; FVC
17.  Traffic exposure and lung function in adults: the Atherosclerosis Risk in Communities study 
Thorax  2007;62(10):873-879.
Background
Traffic exposure is a major contributor to ambient air pollution for people living close to busy roads. The relationship between traffic exposure and lung function remains inconclusive in adults.
Methods
A cross‐sectional study was conducted to investigate the association between traffic exposure and lung function in the Atherosclerosis Risk in Communities (ARIC) study, a community based cohort of 15 792 middle aged men and women. Traffic density and distance to major roads were used as measures of traffic exposure.
Results
After controlling for potential confounders including demographic factors, personal and neighbourhood level socioeconomic characteristics, cigarette smoking and background air pollution, higher traffic density was significantly associated with lower forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in women. Relative to the lowest quartile of traffic density, the adjusted differences across increasing quartiles were 5.1, −15.4 and −21.5 ml for FEV1 (p value of linear trend across the quartiles = 0.041) and 1.2, −23.4 and −34.8 ml for FVC (p trend = 0.010). Using distance from major roads as a simpler index of traffic related air pollution exposure, the FEV1 was −15.7 ml (95% CI −34.4 to 2.9) lower and the FVC was −24.2 ml (95% CI −46.2 to −2.3) lower for women living within 150 m compared with subjects living further away. There was no significant effect of traffic density or distance to major roads on lung function in men. The FEV1/FVC ratio was not significantly associated with traffic exposure in either men or women.
Conclusions
This is the largest published study of traffic exposure and pulmonary function in adults to date. These results add to growing evidence that chronic exposure to traffic related air pollution may adversely affect respiratory health.
doi:10.1136/thx.2006.073015
PMCID: PMC2094260  PMID: 17442705
18.  Diabetes, Impaired Glucose Tolerance, and Metabolic Biomarkers in Individuals with Normal Glucose Tolerance are Inversely Associated with Lung Function: The Jackson Heart Study 
Lung  2011;189(4):311-321.
The objectives of this study were to test the hypothesis that diabetes and impaired glucose tolerance (IGT), diabetes control and diabetes duration, and metabolic biomarkers in adults with normal glucose tolerance (NGT) are inversely associated with spirometry-measured lung function. We conducted a cross-sectional observational cohort study that included nonsmoking African American adults (n = 2,945; mean age = 52.5 ± 12.6 years; 69.2% female), who were free of cardiovascular disease, from the Jackson Heart Study. The interventions were diabetes, metabolic biomarkers and lung function. We measured the associations of glycemia with forced expiratory volume (FEV) in 1 s, FEV in 6 s, and vital capacity. Multivariable adjusted mean lung function values were lower among adults with diabetes and IGT (in women only, but not after adjustment for waist circumference) than adults with NGT. Among adults with diabetes, no associations were observed between lung function and diabetes control or duration. In women with NGT, lower lung function was consistently associated with higher glucose levels and less consistently with higher insulin levels and insulin resistance. Lower lung function was consistently associated with higher insulin levels and insulin resistance and less consistently associated with insulin and hemoglobin A1c in men with NGT. Overall, our findings generally support the hypothesis that diabetes, IGT, and increased levels of metabolic biomarkers in individuals with NGT are inversely associated with lung function in African Americans, independent of adiposity.
doi:10.1007/s00408-011-9296-1
PMCID: PMC3209803  PMID: 21567165
Forced expiratory volume in 1 s; Insulin resistance; Spirometry; Vital capacity; Impaired glucose tolerance
19.  A new staging strategy for chronic obstructive pulmonary disease 
Background:
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.
Method:
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.
Result:
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.
Conclusion:
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
20.  Lung function in young adults: evidence for differences in the chronological age at which various functions start to decline. 
Thorax  1980;35(8):615-619.
In order to gather prospective information on the chronological age at which lung functions start to decline, follow-up measurements were carried out on 38 young adults (30 men and eight women) whose respiratory and cardiac function had been studied previously in the course of a survey of high school students. In the 15 subjects who had reached adult height at the time of the first study, only the vital capacity showed no change between studies, while forced expiratory flow rates (FEV1, MMEF), transfer factor (TLCO) and alveolar volume (VA) all decreased. By contrast, in the 23 subjects who had grown in stature since the previous tests, there was an increase in the slow and forced vital capacity, no consistent change in FEV1 and MMEF, and a decrease in TLCO. The findings are consistent with the view that the age-related decline does not start at the same chronological age for all lung functions, and suggest that structural changes associated with biological "aging" affect some functions before others. The results also illustrate the inadequacy of predicting values for early adulthood by backward extrapolation from later decades or forward extrapolation from the teens, and underline the need for comprehensive studies to elucidate the pattern of change which accompanies growth, maturation, and early adulthood.
PMCID: PMC471345  PMID: 7444830
21.  Diet, lung function, and lung function decline in a cohort of 2512 middle aged men 
Thorax  2000;55(2):102-108.
BACKGROUND—A prospective cohort study of 2512 Welshmen aged 45-59 living in Caerphilly in 1979-1983 was used to investigate associations between diet and lung function.
METHODS—At baseline (phase I) and at five year follow up (phase II), forced expiratory volume in one second (FEV1) was measured using a McDermott spirometer and dietary data were obtained using a semi-quantitative food frequency questionnaire.
RESULTS—Good lung function, indicated by high maximum FEV1 given age and height, was associated with high intakes of vitamin C, vitamin E, β-carotene, citrus fruit, apples, and the frequent consumption of fruit juices/squashes. Lung function was inversely associated with magnesium intake but there was no evidence of an association with fatty fish. Following adjustment for confounders including body mass index, smoking history, social class, exercise, and total energy intake, only the associations with vitamin E and apples persisted, with lung function estimated to be 39 ml (95% confidence interval (CI) 9 to 69) higher for vitamin E intakes one standard deviation (SD) apart and 138 ml higher (95% CI 58to 218) for those eating five or more apples per week compared with non-consumers. Decline in lung function between phases was not significantly associated with the changing intakes of apples or vitamin E. An association between high average apple consumption and slow decline in lung function lost significance after adjustment for confounders.
CONCLUSIONS—A strong positive association is seen between lung function and the number of apples eaten per week cross sectionally, consistent with a protective effect of hard fruit rather than soft/citrus fruit. The recent suggestion that such effects are reversible was not supported by our longitudinal analysis.


doi:10.1136/thorax.55.2.102
PMCID: PMC1745677  PMID: 10639525
22.  Increase in prevalence and severity of asthma in young adults in Copenhagen 
Thorax  2000;55(10):833-836.
BACKGROUND—It is the general impression that the prevalence of asthma has increased during recent decades. A study was undertaken to investigate asthma prevalence, respiratory symptoms, and lung function in young adults in the City of Copenhagen 15 years apart.
METHODS—Men and women aged 20-35 years were sampled from the general population living in a defined area of central Copenhagen. The first examination took place in 1976-8 and comprised 1034 subjects (response rate 67.2%). A new sample comprising 1104 subjects (response rate 62.6%) from exactly the same area was examined 15 years later in 1991-4. All participants answered a questionnaire on respiratory symptoms and diseases and performed spirometric tests with measurement of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).
RESULTS—The prevalence of self-reported asthma increased from 1.5% in the first survey to 4.8% in the second survey (p<0.001). Asthmatic subjects had, on average, poorer lung function than non-asthmatic subjects in terms of FEV1 and this difference was more pronounced in the second survey than in the first (10.0% of predicted versus 2.4% of predicted). Smoking decreased significantly from 62% in 1976-8 to 45% in 1991-4 (p<0.001).
CONCLUSIONS—The prevalence of self-reported asthma has increased significantly among young adults in Copenhagen over a 15 year period. The severity of asthma, as judged by the level of FEV1, has also increased. These findings cannot be explained by changes in smoking habits.


doi:10.1136/thorax.55.10.833
PMCID: PMC1745615  PMID: 10992534
23.  Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis 
Thorax  2004;59(7):574-580.
Background: Individuals with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular diseases, osteoporosis, and muscle wasting. Systemic inflammation may be involved in the pathogenesis of these disorders. A study was undertaken to determine whether systemic inflammation is present in stable COPD.
Methods: A systematic review was conducted of studies which reported on the relationship between COPD, forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC), and levels of various systemic inflammatory markers: C-reactive protein (CRP), fibrinogen, leucocytes, tumour necrosis factor-α (TNF-α), and interleukins 6 and 8. Where possible the results were pooled together to produce a summary estimate using a random or fixed effects model.
Results: Fourteen original studies were identified. Overall, the standardised mean difference in the CRP level between COPD and control subjects was 0.53 units (95% confidence interval (CI) 0.34 to 0.72). The standardised mean difference in the fibrinogen level was 0.47 units (95% CI 0.29 to 0.65). Circulating leucocytes were also higher in COPD than in control subjects (standardised mean difference 0.44 units (95% CI 0.20 to 0.67)), as were serum TNF-α levels (standardised mean difference 0.59 units (95% CI 0.29 to 0.89)).
Conclusions: Reduced lung function is associated with increased levels of systemic inflammatory markers which may have important pathophysiological and therapeutic implications for subjects with stable COPD.
doi:10.1136/thx.2003.019588
PMCID: PMC1747070  PMID: 15223864
24.  Correlation of respiratory symptoms and spirometric lung patterns in a rural community setting, Sindh, Pakistan: a cross sectional survey 
Background
Symptom-based questionnaires can be a cost effective tool enabling identification and diagnosis of patients with respiratory illnesses in resource limited setting. This study aimed to determine the correlation of respiratory symptoms and spirometric lung patterns and validity of ATS respiratory questionnaire in a rural community setting.
Methods
This cross sectional survey was conducted between January – March 2009 on a sample of 200 adults selected from two villages of district Khairpur, Sindh, Pakistan. A modified version of the American thoracic society division of lung disease questionnaire was used to record the presence of respiratory symptoms. Predicted lung volumes i.e. forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and their ratio (FEV1/FVC) were recorded using portable spirometer.
Results
In the study sample there were 91 (45.5%) males and 109 (54.5%) females with overall mean age of 34 years (±11.69). Predominant respiratory symptom was phlegm (19%) followed by cough (17.5%), wheeze (14%) and dyspnea (10.5%). Prevalence of physician diagnosed and self-reported asthma was 5.5% and 9.5% respectively. Frequency of obstructive pattern on spirometry was 28.72% and that of restrictive pattern was 19.68%. After adjustment for age, gender, socioeconomic status, spoken dialect, education, smoking status, height, weight and arsenic in drinking water, FVC was significantly reduced for phlegm (OR 3.01; 95% CI: 1.14 – 7.94), wheeze (OR 7.22; 95% CI: 2.52 – 20.67) and shortness of breath (OR 4.91; 95% CI: 1.57 – 15.36); and FEV1 was significantly reduced for cough (OR 2.69; 95% CI: 1.12 – 6.43), phlegm (OR 3.01; 95% CI: 1.26 – 7.16) and wheeze (OR 10.77; 95% CI: 3.45 – 33.6). Presence of respiratory symptoms was significantly associated with restrictive and/or obstructive patterns after controlling for confounders. Similar findings were observed through linear regression where respiratory symptoms were found to be significantly associated with decrements in lung volumes. Specificity and positive predictive values were found to be higher for all the symptoms compared to sensitivity and negative predictive values.
Conclusion
Symptoms based respiratory questionnaires are a valuable tool for screening of respiratory symptoms in resource poor, rural community setting.
doi:10.1186/1471-2466-12-81
PMCID: PMC3552941  PMID: 23249311
ATS questionnaire validity; Respiratory symptoms; Impaired lung function; Sindhi; Rural community
25.  Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils. 
Thorax  1996;51(3):267-271.
BACKGROUND: Smoking may cause inflammation of the airways and impairment of lung function. To determine the relationship between the type and degree of airways inflammation and the decline in lung function, leucocytes in the sputum of smokers and ex-smokers were examined. METHODS: Forty six smokers and ex-smokers of median age 64 years (25%; 75% percentiles 62;66) with a smoking history of 40.1 (31.7;53) pack years were studied with lung function tests and a questionnaire at the end of a 15 year follow up period. Sputum was induced by inhalation of hypertonic saline and differential leucocyte counts were performed on cytospin preparations. RESULTS: Adequate sputum samples were obtained in 38 subjects (78%). The ratio of forced expiratory volume in one second (FEV1) to vital capacity (VC) was 67.1 (60; 72)% and the annual decline in FEV1 was 19.4 (12;30) ml/year. Subjects with airways obstruction (FEV1/VC < 63%) had more neutrophils (77 (50;86)%) than those without airways obstruction (60 (43;73)%). The percentage of neutrophils was also significantly greater (77 (62;85)%) in those with chronic expectoration than in those without expectoration (57 (45;75)%. Increased levels of neutrophils in the sputum were correlated with a rapid decline in FEV1 over the 15 year follow up period. CONCLUSIONS: Airways obstruction and chronic expectoration, as well as accelerated decline in lung function, are associated with increased numbers of neutrophils in the sputum of smokers and ex-smokers which suggests that neutrophilic inflammation of the airways may be involved in the pathogenesis of chronic obstructive pulmonary disease.
Images
PMCID: PMC1090637  PMID: 8779129

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