Respiratory Abstracts 4

© 2013

Exhaled nitric oxide in diagnosis and management of respiratory diseases

            (Abba 2009) Download

The analysis of biomarkers in exhaled breath constituents has recently become of great interest in the diagnosis, treatment and monitoring of many respiratory conditions. Of particular interest is the measurement of fractional exhaled nitric oxide (FENO) in breath. Its measurement is noninvasive, easy and reproducible. The technique has recently been standardized by both American Thoracic Society and European Respiratory Society. The availability of cheap, portable and reliable equipment has made the assay possible in clinics by general physicians and, in the near future, at home by patients. The concentration of exhaled nitric oxide is markedly elevated in bronchial asthma and is positively related to the degree of esinophilic inflammation. Its measurement can be used in the diagnosis of bronchial asthma and titration of dose of steroids as well as to identify steroid responsive patients in chronic obstructive pulmonary disease. In primary ciliary dyskinesia, nasal NO is diagnostically low and of considerable value in diagnosis. Among lung transplant recipients, FENO can be of great value in the early detection of infection, bronchioloitis obliterans syndrome and rejection. This review discusses the biology, factors affecting measurement, and clinical application of FENO in the diagnosis and management of respiratory diseases.

Exhaled nitric oxide and urinary EPX levels in infants: a pilot study

            (Carlstedt, Lazowska et al. 2011) Download

BACKGROUND: Objective markers of early airway inflammation in infants are not established but are of great interest in a scientific setting. Exhaled nitric oxide (FeNO) and urinary eosinophilic protein X (uEPX) are a two such interesting markers. OBJECTIVE: To investigate the feasibility of measuring FeNO and uEPX in infants and their mothers and to determine if any relations between these two variables and environmental factors can be seen in a small sample size. This was conducted as a pilot study for the ongoing Swedish Environmental Longitudinal Mother and child Asthma and allergy study (SELMA). METHODS: Consecutive infants between two and six months old and their mothers at children's health care centres were invited, and 110 mother-infant pairs participated. FeNO and uEPX were analysed in both mothers and infants. FeNO was analyzed in the mothers online by the use of the handheld Niox Mino device and in the infants offline from exhaled air sampled during tidal breathing. A 33-question multiple-choice questionnaire that dealt with symptoms of allergic disease, heredity, and housing characteristics was used. RESULTS: FeNO levels were reduced in infants with a history of upper respiratory symptoms during the previous two weeks (p < 0.002). There was a trend towards higher FeNO levels in infants with windowpane condensation in the home (p < 0.05). There was no association between uEPX in the infants and the other studied variables. CONCLUSION: The use of uEPX as a marker of early inflammation was not supported. FeNO levels in infants were associated to windowpane condensation. Measuring FeNO by the present method may be an interesting way of evaluating early airway inflammation. In a major population study, however, the method is difficult to use, for practical reasons.

Inadequate glucose control in type 2 diabetes is associated with impaired lung function and systemic inflammation: a cross-sectional study

            (Dennis, Maldonado et al. 2010) Download

BACKGROUND: Inadequate glucose control may be simultaneously associated with inflammation and decreased lung function in type 2 diabetes. We evaluated if lung function is worse in patients with inadequate glucose control, and if inflammatory markers are simultaneously increased in these subjects. METHODS: Subjects were selected at the Colombian Diabetes Association Center in Bogota. Pulmonary function tests were performed and mean residual values were obtained for forced expiratory volume (FEV1), forced vital capacity (FVC) and FEV1/FVC, with predicted values based on those derived by Hankinson et al. for Mexican-Americans. Multiple least-squares regression was used to adjust for differences in known determinants of lung function. We measured blood levels of glycosylated hemoglobin (HBA1c), interleukin 6 (IL-6), tumor necrosis factor (TNF-alpha), fibrinogen, ferritin, and C-reactive protein (C-RP). RESULTS: 495 diabetic patients were studied, out of which 352 had inadequate control (HBA1c > 7%). After adjusting for known determinants of lung function, those with inadequate control had lower FEV1 (-75.4 mL, IC95%: -92, -59; P < 0.0001) and FVC (-121 mL, IC95%: -134, -108; P < 0,0001) mean residuals, and higher FEV1/FVC (0.013%, IC95%: 0.009, 0.018, P < 0.0001) residuals than those with adequate control, as well as increased levels of all inflammatory markers (P < 0.05), with the exception of IL-6. CONCLUSIONS: Subjects with type 2 diabetes and inadequate control had lower FVC and FEV1 than predicted and than those of subjects with adequate control. It is postulated that poorer pulmonary function may be associated with increased levels of inflammatory mediators.


Effects of the menstrual cycle on lung function variables in women with asthma

         (Farha, Asosingh et al. 2009) Download

RATIONALE: Angiogenesis is a defining pathologic feature of airway remodeling and contributes to asthma severity. Women experience changes in asthma control over the menstrual cycle, a time when vessels routinely form and regress under the control of angiogenic factors. One vital function modulated over the menstrual cycle in healthy women is gas transfer, and this has been related to angiogenesis and cyclic expansion of the pulmonary vascular bed. OBJECTIVES: We hypothesized that changes in gas transfer and the pulmonary vascular bed occur in women with asthma over the menstrual cycle and are associated with worsening airflow obstruction. METHODS: Twenty-three women, 13 with asthma and 10 healthy control subjects, were evaluated over the menstrual cycle with weekly measures of spirometry, gas transfer, nitric oxide, hemoglobin, factors affecting hemoglobin binding affinity, and proangiogenic factors. MEASUREMENTS AND MAIN RESULTS: Airflow and lung diffusing capacity varied over the menstrual cycle with peak levels during menses that subsequently declined to nadir in early luteal phase. In contrast to healthy women, changes in lung diffusing capacity (DL(CO)) were associated with changes in membrane diffusing capacity and DL(CO) was not related to proangiogenic factors. DL(CO) did not differ between the two groups, although methemoglobin and carboxyhemoglobin were higher in women with asthma than in healthy women. CONCLUSIONS: Women with asthma experience cyclic changes in airflow as well as gas transfer and membrane diffusing capacity supportive of a hormonal effect on lung function.

The association between blood coagulation activity and lung function: a population-based study

            (Fogarty, Lewis et al. 2010) Download

BACKGROUND: Increased in susceptibility to thrombotic disease may be associated with lower lung function. If causal, this association may suggest an area for development of new interventions for lung disease. The aim of this study was to investigate the association between blood coagulation activation as measured by plasma d-dimers and lung function. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional study on 2463 randomly selected adults in 1991 and followed up 1252 of these individuals in 2000. Plasma D-dimer levels, a marker of activity of blood coagulation pathways, were analysed in the baseline 1991 samples. There was an inverse cross-sectional association between plasma D-dimer and Forced Expiratory Volume in one second, with a decrease of 71 ml per microg FEU/ml increment in plasma D-dimer (95% confidence intervals CI: -135 to -6), and a decrease in Forced Vital Capacity (97 ml per microg FEU/ml increase in D-dimer, 95%CI: -170 to -24). These associations were attenuated after adjustment for serum highly sensitive CRP. No association was observed between plasma D-dimer and the decline in lung function between 1991 and 2000. CONCLUSIONS/SIGNIFICANCE: The cross-sectional findings are consistent with the hypothesis that activation of blood coagulation pathways is associated with decreased lung function, and that systemic inflammation may contribute to this relation. However, the lack of an association with decline in lung function suggests that clotting pathways that involve d-dimers may not be a promising therapeutic target for new interventions for respiratory disease.

Association of CRP and IL-6 with lung function in a middle-aged population initially free from self-reported respiratory problems: the Whitehall II study

            (Gimeno, Delclos et al. 2011) Download

To assess whether two inflammatory markers, C-reactive protein (CRP) and interleukin-6 (IL-6), and change in their concentrations over 12 years, are associated with lung function (FVC and FEV(1)) 12 years after baseline. Data are from over 1,500 participants free from self-reported respiratory problems in a large-scale prospective cohort study of white-collar male and female civil servants. CRP and IL-6 measured at baseline (1991-1993) and follow-up (2002-2004) and FVC and FEV(1), measured at follow-up. Results adjusted for sociodemographic and anthropometric characteristics, health behaviours, biological factors, chronic conditions and medications, and corrected for short-term variability in CRP and IL-6 concentrations. Higher baseline levels of CRP and IL-6 were strongly associated with lower FVC and FEV(1), independent of potential confounders. A 10% increase serum CRP from baseline to follow-up was associated with lower values of FVC and FEV(1) at follow-up, 4.7 and 3.0 ml, respectively. The corresponding values for a 10% increase in IL-6 were 12.6 ml for FVC and 7.3 ml for FEV(1). Systemic low-grade inflammation is associated with only slightly poorer pulmonary function in a population free from self-reported respiratory problems 12 years earlier. These data provide evidence linking inflammation to adverse outcomes beyond cardiovascular disease. Interventions targeting inflammation may prevent lung function impairment.


Serum carotenoids, vitamins A and E, and 8 year lung function decline in a general population

         (Guenegou, Leynaert et al. 2006) Download

BACKGROUND: Oxidative stress is thought to have a major role in the pathogenesis of airway obstruction. A study was undertaken to determine whether subjects with low levels of antioxidants (serum beta-carotene, alpha-carotene, vitamins A and E) would be at a higher risk of accelerated decline in forced expiratory volume in 1 second (FEV1) as their lungs would be less protected against oxidative stress. METHODS: 1194 French subjects aged 20-44 years were examined in 1992 as part of the European Community Respiratory Health Survey (ECRHS); 864 were followed up in 2000 and 535 (50% men, 40% lifelong non-smokers) had complete data for analysis. RESULTS: During the 8 year study period the mean annual decrease in FEV1 (adjusted for sex, centre, baseline FEV1, age, smoking, body mass index and low density lipoprotein cholesterol) was 29.8 ml/year. The rate of decrease was lower for the subjects in tertile I of beta-carotene at baseline than for those in the two other tertiles (-36.5 v -27.6 ml/year; p = 0.004). An increase in beta-carotene between the two surveys was associated with a slower decline in FEV1. No association was observed between alpha-carotene, vitamin A, or vitamin E and FEV(1) decline. However, being a heavy smoker (> or =20 cigarettes/day) in combination with a low level of beta-carotene or vitamin E was associated with the steepest decline in FEV1 (-52.5 ml/year, p = 0.0002 and -50.1 ml/year, p = 0.010, respectively). CONCLUSIONS: These results strongly suggest that beta-carotene protects against the decline in FEV1 over an 8 year period in the general population, and that beta-carotene and vitamin E are protective in heavy smokers.

Systemic inflammation and lung function in young adults

         (Hancox, Poulton et al. 2007) Download

BACKGROUND: Impaired lung function is associated with systemic inflammation and is a risk factor for cardiovascular disease in older adults. It is unknown when these associations emerge and to what extent they are mediated by smoking, chronic airways disease, and/or established atherosclerosis. We explored the association between the forced expiratory volume in one second (FEV(1)) and the systemic inflammatory marker C-reactive protein (CRP) in young adults. METHODS: Associations between spirometric lung function and blood CRP were assessed in a population based birth cohort of approximately 1000 New Zealanders at ages 26 and 32 years. Analyses adjusted for height and sex to account for differences in predicted lung function and excluded pregnant women. RESULTS: There were significant inverse associations between FEV(1) and CRP at both ages. Similar results were found for the forced vital capacity. These associations were similar in men and women and were independent of smoking, asthma, and body mass index. CONCLUSIONS: Reduced lung function is associated with systemic inflammation in young adults. This association is not related to smoking, asthma, or obesity. The reasons for the association are unexplained, but the findings indicate that the association between lower lung function and increased inflammation predates the development of either chronic lung disease or clinically significant atherosclerosis. The association between poor lung function and cardiovascular disease may be mediated by an inflammatory mechanism.

Diabetes, impaired glucose tolerance, and metabolic biomarkers in individuals with normal glucose tolerance are inversely associated with lung function: the Jackson Heart Study

            (Hickson, Burchfiel et al. 2011) Download

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.


Systemic inflammation in young adults is associated with abnormal lung function in middle age

            (Kalhan, Tran et al. 2010) Download

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 (FEV(1)) (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 FEV(1) (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 FEV(1). 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.

Reduced lung function is independently associated with increased risk of type 2 diabetes in Korean men

         (Kwon, Rhee et al. 2012) Download

BACKGROUND: Reduced lung function is associated with incident insulin resistance and diabetes. The aim of this study was to assess the relationship between lung function and incident type 2 diabetes in Korean men. METHODS: This study included 9,220 men (mean age: 41.4 years) without type 2 diabetes at baseline who were followed for five years. Subjects were divided into four groups according to baseline forced vital capacity (FVC) (% predicted) and forced expiratory volume in one second (FEV1) (% predicted) quartiles. The incidence of type 2 diabetes at follow-up was compared according to FVC and FEV1 quartiles. RESULTS: The overall incidence of type 2 diabetes was 2.2%. Reduced lung function was significantly associated with the incidence of type 2 diabetes after adjusting for age, BMI, education, smoking, exercise, alcohol, and HOMA-IR. Both FVC and FEV1 were negatively associated with type 2 diabetes (P < 0.05). In non-obese subjects with BMI < 25, the lowest quartile of FVC and FEV1 had a significantly higher odds ratio for type 2 diabetes compared with the highest quartile after adjusting for age and BMI (2.15 [95% CI 1.02-4.57] and 2.19 [95% CI 1.09-4.42]). CONCLUSIONS: Reduced lung function is independently associated with the incidence of type 2 diabetes in Korean men.

Vitamin D deficiency is associated with decreased lung function in Chinese adults with asthma

         (Li, Peng et al. 2011) Download

BACKGROUND: Vitamin D deficiency has been associated with markers for allergy and asthma severity in children with asthma. However, its association with Chinese adult asthmatics has not been studied. OBJECTIVE: To examine whether vitamin D status is associated with lung function and total serum IgE in Chinese adults with newly diagnosed asthma. METHODS: We conducted a cross-sectional study including 435 Chinese patients aged >18 years with newly diagnosed asthma. Vitamin D status was assessed by measuring serum 25 hydroxyvitamin D (25OHD) concentrations. The primary outcomes included airflow limitation, as measured by the forced expiratory volume in 1 s (FEV(1)), FEV(1) % predicted, and FEV(1)/forced vital capacity (FVC), and serum total IgE concentration. RESULTS: Vitamin D deficiency was prevalent in Chinese adults with asthma, with 88.9% of the subjects having 25OHD <50 nmol/l. Serum 25OHD concentration was positively correlated with FEV(1) % predicted (p = 0.02, r = 0.12). After adjusting for age, sex, body mass index, smoking, month of blood collection, and symptom duration, we found significant positive associations between 25OHD concentrations and FEV(1) (in liters), FEV(1) % predicted, and FEV(1)/FVC (p for trend < 0.05 for all). The adjusted odds ratios for the highest versus the lowest 25OHD quartile were 0.50 (0.26-0.96) for FEV(1) <75% predicted and 0.44 (0.20-0.95) for FEV(1)/FVC% <0.75. There was no significant association between 25OHD concentrations and total IgE. CONCLUSIONS: Vitamin D deficiency was highly prevalent in Chinese asthma patients, and vitamin D status was associated with lung function.


Urinary cadmium levels predict lower lung function in current and former smokers: data from the Third National Health and Nutrition Examination Survey

            (Mannino, Holguin et al. 2004) Download

BACKGROUND: A study was undertaken to determine the relation between urinary cadmium levels and lung function in a nationally representative cohort of current, former, and never smokers in the US. Urinary cadmium levels reflect the total body burden of cadmium. METHODS: The following data from the Third National Health and Nutrition Examination Survey were analysed: urinary cadmium (adjusted for urinary creatinine), lung function, sex, race/ethnicity, age, education level, job category, body mass index, serum cotinine level, and smoking history. Linear regression models were developed to predict lung function using urinary cadmium as the main predictor, adjusting for other covariates and stratified by smoking status. RESULTS: Data were available on 16 024 adults. Current smokers had higher mean (SE) urinary cadmium/creatinine levels (0.46 (0.01) micro g/g) than former (0.32 (0.01) micro g/g) or never smokers (0.23 (0.01) micro g/g). Higher levels of urinary cadmium were associated with significantly lower forced expiratory volumes in 1 second (FEV(1)) in current (-2.06%, 95% confidence interval (CI) -2.86 to -1.26 per 1 log increase in urinary cadmium) and former smokers (-1.95%, 95% CI -2.87 to -1.03) but not in never smokers (-0.18%, 95% CI -0.60 to 0.24). Similar results were obtained for forced vital capacity (FVC) and FEV(1)/FVC. CONCLUSIONS: Cadmium, which is known to cause emphysema in occupational settings, may also be important in the development of tobacco related lung disease.

Time for new reference values for ventilatory lung function

         (Marek, Marek et al. 2009) Download

OBJECTIVE: The anthropometrical data of our aging population has significantly changed within the last five decades. Therefore the question arises whether or not the commonly used reference values of the European Community (ECCS) for lung function, may still be accepted today. Measured values for elderly are classified by extrapolation beyond the range of reference equations. MATERIAL AND METHODS: Lung function was examined by pneumotachography for recording static lung volumes and flow-volume-curves in 257 asymptomatic non smoking males, aged 20-90 years. Results were compared to the reference values of ECCS, SAPALDIA, LuftiBus, and NHANES. RESULTS: For analysis age and height dependence of investigated respiratory parameters (VC, FVC, FEV(1), FEV(1) %FVC, PEF, MEF(75,50,25)) can for simplicity be described by linear functions (y = a . height(H)-b . age (A)+c). The forced expiratory volume in one second, FEV(1), was calculated by FEV(1) = 0.0432 . H-0.0347 . A -2.114; where H - height, A - age; r = 0.78. Mean FEV(1) for younger subjects was found to be 106.1 +/- 11.2% of the ECCS reference values and 97.8 +/- 11.7% in older subjects. For all parameters investigated linear regressions on age were steeper than described by the ECCS reference values. The regression of lung function to height largely follows the ECCS prescriptions. SUMMARY: Bochum lung function values of healthy subjects showed a steeper age descent compared to the reference values of the ECCS. The alternatively discussed reference values of the SAPALDIA-, NHANES- or LuftiBus-Study are higher, but do not cover all necessary parameters and/or the age range. A multi centre study for contemporary reference values is recommended.

Lung function in our aging population

         (Marek, Marek et al. 2011) Download

AIMS OF INVESTIGATION: The chronological age of the Caucasian population and their anthropometrical data have significantly changed within the last five decades. Therefore the question arises whether or not the commonly used reference values of the European Community (ECCS) for lung function may still be accepted today. Since these values were obtained in the 1960s from subjects in a limited age range. For the elderly, the measured values are deduced by extrapolation beyond the range of reference equations which had been obtained in a different population. Therefore decisions concerning elderly and smaller subjects concerning remuneration due to impaired lung function after industrial exposure on the basis of EGKS values are questionable. METHODS: Lung function tests were performed by pneumotachography, recording static lung volumes and flow-volume-curves in 262 asymptomatic non smoking males, aged 20 to 90 years. Measurements were performed with the MasterLab, or PneumoScreen systems (CareFusion, Hochberg). Results were compared to the reference values of ECCS, SAPALDIA and LuftiBus. - Results: For simplicity analysis of age and height dependence of investigated respiratory parameters (VC, FVC, FEV subset1, FEV subset1%FVC, PEF, MEF subset75,50,25) can be described by linear functions (y = a * height ? b * age + c). The forced expiratory vital capacity, FVC, was calculated by FVC = 0.0615*H - 0.0308*A - 4.673; r = 0.78. Mean FVC for younger subjects was found to be 104.7 +/- 10.7% of the ECCS reference values and 96.5 +/- 11.8 % in older subjects. For most parameters investigated linear regressions on age were steeper than described by the ECCS reference values. The regression of lung function to height largely follows the ECCS prescriptions. SUMMARY: Bochum lung function values of younger healthy subjects were higher compared to the reference values of the ECCS and showed a steeper age descent. The alternatively discussed reference values of the SAPALDIA-, or LuftiBus-Study are higher, but do not cover all necessary parameters and/or the age range. A multi centre study for contemporary reference values is recommended.


A multivariate analysis of serum nutrient levels and lung function

         (McKeever, Lewis et al. 2008) Download

BACKGROUND: There is mounting evidence that estimates of intakes of a range of dietary nutrients are related to both lung function level and rate of decline, but far less evidence on the relation between lung function and objective measures of serum levels of individual nutrients. The aim of this study was to conduct a comprehensive examination of the independent associations of a wide range of serum markers of nutritional status with lung function, measured as the one-second forced expiratory volume (FEV1). METHODS: Using data from the Third National Health and Nutrition Examination Survey, a US population-based cross-sectional study, we investigated the relation between 21 serum markers of potentially relevant nutrients and FEV1, with adjustment for potential confounding factors. Systematic approaches were used to guide the analysis. RESULTS: In a mutually adjusted model, higher serum levels of antioxidant vitamins (vitamin A, beta-cryptoxanthin, vitamin C, vitamin E), selenium, normalized calcium, chloride, and iron were independently associated with higher levels of FEV1. Higher concentrations of potassium and sodium were associated with lower FEV1. CONCLUSION: Maintaining higher serum concentrations of dietary antioxidant vitamins and selenium is potentially beneficial to lung health. In addition other novel associations found in this study merit further investigation.

The association between systemic inflammatory cellular levels and lung function: a population-based study

            (McKeever, Saha et al. 2011) Download

BACKGROUND: Lower lung function is associated with an elevated systemic white cell count in men. However, these observations have not been demonstrated in a representative population that includes females and may be susceptible to confounding by recent airway infections or recent cigarette smoking. We tested the hypothesis that lung function is inversely associated with systemic white cell count in a population-based study. METHODS: The study population consisted adults aged 17-90+ years who participated in the Third National Health and Nutrition Examination Survey who did not report a recent cough, cold or acute illness in a non-smoking and smoking population. RESULTS: In non-smoking adults with the highest quintile of the total white cell count had a FEV(1) 125.3 ml lower than those in the lowest quintile (95% confidence interval CI: -163.1 to -87.5). Adults with the highest quintile of the total white cell count had a FVC 151.1 ml lower than those in the lowest quintile (95% confidence interval CI: -195.0 to -107.2). Similar associations were observed for granulocytes, mononuclear cells and lymphocytes. In current smokers, similar smaller associations observed for total white cell count, granulocytes and mononuclear cells. CONCLUSIONS: Systemic cellular inflammation levels are inversely associated with lung function in a population of both non-smokers and smokers without acute illnesses. This may contribute to the increased mortality observed in individuals with a higher baseline white cell count.

Curcumins-rich curry diet and pulmonary function in asian older adults

         (Ng, Niti et al. 2012) Download

BACKGROUND: Research on the effects of dietary nutrients on respiratory health in human populations have not investigated curcumin, a potent anti-oxidant and anti-inflammatory compound present principally in turmeric used in large amounts in Asian curry meals. OBJECTIVES: To examine the association of curry intake with pulmonary function among smokers and non-smokers. DESIGN: The frequency of curry intake, respiratory risk factors and spirometry were measured in a population-based study of 2,478 Chinese older adults aged 55 and above in the Singapore Longitudinal Ageing Studies. RESULTS: Curry intake (at least once monthly) was significantly associated with better FEV(1) (b = 0.045+/-0.018, p = 0.011) and FEV(1)/FVC (b = 1.14+/-0.52, p = 0.029) in multivariate analyses that controlled simultaneously for gender, age, height, height-squared, smoking, occupational exposure and asthma/COPD history and other dietary or supplementary intakes. Increasing levels of curry intake ('never or rarely', 'occasional', 'often', 'very often') were associated with higher mean adjusted FEV(1) (p for linear trend = 0.001) and FEV(1)/FVC% (p for linear trend = 0.048). Significant effect modifications were observed for FEV(1) (curry* smoking interaction, p = 0.028) and FEV(1)/FVC% (curry*smoking interaction, p = 0.05). There were significantly larger differences in FEV(1) and FEV(1)/FVC% between curry intake and non-curry intake especially among current and past smokers. The mean adjusted FEV(1) associated with curry intake was 9.2% higher among current smokers, 10.3% higher among past smokers, and 1.5% higher among non-smokers. CONCLUSION: The possible role of curcumins in protecting the pulmonary function of smokers should be investigated in further clinical studies.

Lung function and blood markers of nutritional status in non-COPD aging men with smoking history: a cross-sectional study

            (Shiozawa, Hayashimoto et al. 2010) Download

PURPOSE: Cigarette smoking and advanced age are well known as risk factors for chronic obstructive pulmonary disease (COPD), and nutritional abnormalities are important in patients with COPD. However, little is known about the nutritional status in non-COPD aging men with smoking history. We therefore investigated whether reduced lung function is associated with lower blood markers of nutritional status in those men. SUBJECTS AND METHODS: This association was examined in a cross-sectional study of 65 Japanese male current or former smokers aged 50 to 80 years: 48 without COPD (non-COPD group), divided into tertiles according to forced expiratory volume in one second as percent of forced vital capacity (FEV(1)/FVC), and 17 with COPD (COPD group). RESULTS: After adjustment for potential confounders, lower FEV(1)/FVC was significantly associated with lower red blood cell count (RBCc), hemoglobin, and total protein (TP); not with total energy intake. The difference in adjusted RBCc and TP among the non-COPD group tertiles was greater than that between the bottom tertile in the non-COPD group and the COPD group. CONCLUSION: In non-COPD aging men with smoking history, trends toward reduced nutritional status and anemia may independently emerge in blood components along with decreased lung function even before COPD onset.

Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children

            (Steerenberg, Janssen et al. 2003) Download

BACKGROUND: Exhaled nitric oxide (eNO) may serve as a non-invasive marker of airway inflammation but its relationship with other commonly used measures has not been evaluated. METHODS: Levels of eNO in a sample of 450 children aged 7-12 years out of a total sample of 2504 school children living in different urban areas near motorways were determined. The aim of this cross-sectional study was to explore the relationship between eNO, impairment of lung function (PEF, FVC, FEV(1) and MMEF), bronchial hyperresponsiveness (BHR), and blood eosinophilia in children with and without atopy as assessed by skin prick testing. RESULTS: Regression analysis showed that wheezing and nasal discharge and conjunctivitis that had occurred during the previous 12 months were positively associated with eNO levels in atopic children (relative increase of 1.48 and 1.41, respectively; p<0.05) but not in non-atopic children. Similarly, BHR and the number of blood eosinophils per ml were positively associated with eNO levels in atopic children (relative increase of 1.55 and 2.29, respectively; p<0.05) but not in non-atopic children. The lung function indices PEF, FVC, FEV(1) and MMEF were not associated with eNO levels. CONCLUSIONS: In addition to conventional lung function tests and symptom questionnaires, eNO is a suitable measure of airway inflammation and its application may reinforce the power of epidemiological surveys on respiratory health.


Vitamin D levels, lung function, and steroid response in adult asthma

         (Sutherland, Goleva et al. 2010) Download

RATIONALE: Patients with asthma exhibit variable response to inhaled corticosteroids (ICS). Vitamin D is hypothesized to exert effects on phenotype and glucocorticoid (GC) response in asthma. OBJECTIVES: To determine the effect of vitamin D levels on phenotype and GC response in asthma. METHODS: Nonsmoking adults with asthma were enrolled in a study assessing the relationship between serum 25(OH)D (vitamin D) concentrations and lung function, airway hyperresponsiveness (AHR), and GC response, as measured by dexamethasone-induced expression of mitogen-activated protein kinase phosphatase (MKP)-1 by peripheral blood mononuclear cells. MEASUREMENTS AND MAIN RESULTS: A total of 54 adults with asthma (FEV(1), 82.9 +/- 15.7% predicted [mean +/- SD], serum vitamin D levels of 28.1 +/- 10.2 ng/ml) were enrolled. Higher vitamin D levels were associated with greater lung function, with a 22.7 (+/-9.3) ml (mean +/- SE) increase in FEV(1) for each nanogram per milliliter increase in vitamin D (P = 0.02). Participants with vitamin D insufficiency (<30 ng/ml) demonstrated increased AHR, with a provocative concentration of methacholine inducing a 20% fall in FEV(1) of 1.03 (+/-0.2) mg/ml versus 1.92 (+/-0.2) mg/ml in those with vitamin D of 30 ng/ml or higher (P = 0.01). In ICS-untreated participants, dexamethasone-induced MKP-1 expression increased with higher vitamin D levels, with a 0.05 (+/-0.02)-fold increase (P = 0.02) in MKP-1 expression observed for each nanogram per milliliter increase in vitamin D, a finding that occurred in the absence of a significant increase in IL-10 expression. CONCLUSIONS: In asthma, reduced vitamin D levels are associated with impaired lung function, increased AHR, and reduced GC response, suggesting that supplementation of vitamin D levels in patients with asthma may improve multiple parameters of asthma severity and treatment response. Clinical trials registered with www.clinicaltrials.gov (NCT00495157, NCT00565266, and NCT00557180).

The role of female hormones on lung function in chronic lung diseases

         (Tam, Morrish et al. 2011) Download

BACKGROUND: The prevalence, morbidity, and mortality of inflammatory lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are increasing in women. There is a dearth of data on the biological mechanisms to explain such observations. However, some large epidemiologic studies suggest that lung function fluctuates during the menstrual cycle in female patients with airways disease but not in women without disease, suggesting that circulating estradiol and progesterone may be involved in this process. DISCUSSION: In asthma, estradiol shuttles adaptive immunity towards the TH2 phenotype while in smokers estrogens may be involved in the generation of toxic intermediate metabolites in the airways of female smokers, which may be relevant in COPD pathogenesis. In CF, estradiol has been demonstrated to up-regulate MUC5B gene in human airway epithelial cells and inhibit chloride secretion in the airways. Progesterone may augment airway inflammation. SUMMARY: Taken together, clinical and in-vivo data have demonstrated a sex-related difference in that females may be more susceptible to the pathogenesis of lung diseases. In this paper, we review the effect of female sex hormones in the context of these inflammatory airway diseases.

Serum adiponectin is positively associated with lung function in young adults, independent of obesity: the CARDIA study

            (Thyagarajan, Jacobs et al. 2010) Download

RATIONALE: Adipose tissue produces adiponectin, an anti-inflammatory protein. Adiponectin deficiency in mice is associated with abnormal post-natal alveolar development. OBJECTIVE: We hypothesized that lower serum adiponectin concentrations are associated with lower lung function in humans, independent of obesity. We explored mediation of this association by insulin resistance and systemic inflammation. METHODS AND MEASUREMENTS: Spirometry testing was conducted at years 10 and 20 follow-up evaluation visits in 2,056 eligible young adult participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Body mass index, serum adiponectin, serum C-reactive protein (a marker of systemic inflammation), and insulin resistance were assessed at year 15. MAIN RESULTS: After controlling for body mass index, years 10 and 20 forced vital capacity (FVC) were 81 ml and 82 ml lower respectively (p = 0.004 and 0.01 respectively) in the lowest vs. highest adiponectin quartiles. Similarly, years 10 and 20 forced expiratory volume in one second (FEV1) were 50 ml and 38 ml lower (p = 0.01 and 0.09, respectively) in the lowest vs. highest adiponectin quartiles. These associations were no longer significant after adjustment for insulin resistance and C-reactive protein. Serum adiponectin was not associated with FEV1/FVC or peak FEV1. CONCLUSIONS: Independent of obesity, lower serum adiponectin concentrations are associated with lower lung function. The attenuation of this association after adjustment for insulin resistance and systemic inflammation suggests that these covariates are on a causal pathway linking adiponectin and lung function.


Serum carotenoid concentrations predict lung function evolution in young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) study

            (Thyagarajan, K et al. 2011) Download

BACKGROUND: A higher dietary intake of carotenoid-rich foods and higher circulating concentrations of carotenoids have been associated with better lung function in cross-sectional studies; however, the longitudinal association between carotenoids and lung function has shown conflicting results. OBJECTIVE: We examined the longitudinal association between serum carotenoids (beta-cryptoxanthin, alpha-carotene, beta-carotene, lutein/zeaxanthin, and lycopene) and the evolution of lung function. DESIGN: We evaluated our hypothesis in the Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study. Spirometry testing was conducted at year 0 (1985-1986) and at follow-up in years 2, 5, 10, and 20; serum carotenoids were assayed at years 0 and 15, and diet was assessed at years 0 and 20. RESULTS: Year 0 sum of provitamin A carotenoids and beta-cryptoxanthin concentrations were associated with maximum forced vital capacity (FVC) (P </= 0.01) and forced expiratory volume in 1 s (FEV(1)) (P </= 0.05) (maximum across years 0-10) in linear regression models adjusted for age, race, height, study center, amount of physical activity, smoking status, and BMI. Year 0 lutein/zeaxanthin and lycopene were not associated with maximum lung function. Baseline concentrations of lutein/zeaxanthin, lycopene, sum of the 3 provitamin A carotenoids, beta-carotene, and beta-cryptoxanthin were each inversely associated with a decline from maximum FVC and FEV(1) (P </= 0.04). The sum of provitamin A carotenoids and lycopene remained significant after adjustment for dietary intake related to serum carotenoids (P </= 0.03). The 15-y change in provitamin A carotenoid and lutein/zeaxanthin concentrations was associated with a slower decline from maximum FVC and FEV(1) (P </= 0.04). CONCLUSION: These findings support an association between serum carotenoid concentrations and a decline in lung function.


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