Restricted spirometry and cardiometabolic comorbidities: results from the international population based BOLD study.

BACKGROUND: Whether restricted spirometry, i.e. low Forced Vital Capacity (FVC), predicts chronic cardiometabolic disease is not definitely known. In this international population-based study, we assessed the relationship between restricted spirometry and cardiometabolic comorbidities. METHODS: A total of 23,623 subjects (47.5% males, 19.0% current smokers, age: 55.1 ± 10.8 years) from five continents (33 sites in 29 countries) participating in the Burden of Obstructive Lung Disease (BOLD) study were included. Restricted spirometry was defined as post-bronchodilator FVC < 5th percentile of reference values. Self-reports of physician-diagnosed cardiovascular disease (CVD; heart disease or stroke), hypertension, and diabetes were obtained through questionnaires. RESULTS: Overall 31.7% of participants had restricted spirometry. However, prevalence of restricted spirometry varied approximately ten-fold, and was lowest (8.5%) in Vancouver (Canada) and highest in Sri Lanka (81.3%). Crude odds ratios for the association with restricted spirometry were 1.60 (95% CI 1.37-1.86) for CVD, 1.53 (95% CI 1.40-1.66) for hypertension, and 1.98 (95% CI 1.71-2.29) for diabetes. After adjustment for age, sex, education, Body Mass Index (BMI) and smoking, the odds ratios were 1.54 (95% CI 1.33-1.79) for CVD, 1.50 (95% CI 1.39-1.63) for hypertension, and 1.86 (95% CI 1.59-2.17) for diabetes. CONCLUSION: In this population-based, international, multi-site study, restricted spirometry associates with cardiometabolic diseases. The magnitude of these associations appears unattenuated when cardiometabolic risk factors are taken into account.

Chronic airflow obstruction and ambient particulate air pollution.

Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised.

Mass spectrometry-based metabolomics for the discovery of candidate markers of flavonoid and polyphenolic intake in adults.

Robust biological markers of dietary exposure are essential in improving the understanding of the link between diet and health outcomes. Polyphenolic compounds, including flavonoids, have been proposed to mitigate the risk of chronic diseases where oxidative stress and inflammation play a central role. Biomarkers can provide objective measurement of the levels of polyphenolic compounds. In this study, we provide methodology to identify potential candidate markers of polyphenol intake in human serum. Seventeen participants from the UK arm of the Global Allergy and Asthma Network of Excellence (GA2LEN) had their dietary intake estimated using a validated food frequency questionnaire, and serum samples were assessed using mass spectrometry to identify potential candidate markers. 144 features were assigned identities, of these we identified four biologically relevant compounds (rhamnazin 3-rutinoside, 2-galloyl-1,4-galactarolactone methyl ester, 2″,32″-di-O-p-coumaroylafzelin and cyclocommunin), which were significantly increased in the serum of participants with high predicted level of fruit and vegetable intake. 2-galloyl-1,4-galactarolactone methyl ester was strongly correlated with total flavonoids (r = 0.62; P = 0.005), flavan-3-ols (r = 0.67; P = 0.002) as well as with other four subclasses. Rhamnazin 3-rutinoside showed strong correlation with pro-anthocyanidins (r = 0.68; P = 0.001), flavones (r = 0.62; P = 0.005). Our results suggest that serum profiling for these compounds might be an effective way of establishing the relative intake of flavonoids and could contribute to improve the accuracy of epidemiological methods to ascertain flavonoid intake.

Predictors of Food Sensitization in Children and Adults Across Europe.

BACKGROUND: The geographical variation and temporal increase in the prevalence of food sensitization (FS) suggest environmental influences. OBJECTIVE: To investigate how environment, infant diet, and demographic characteristics, are associated with FS in children and adults, focusing on early-life exposures. METHODS: Data on childhood and adult environmental exposures (including, among others, sibship size, day care, pets, farm environment, and smoking), infant diet (including breast-feeding and timing of introduction to infant formula and solids), and demographic characteristics were collected from 2196 school-age children and 2185 adults completing an extensive questionnaire and blood sampling in the cross-sectional pan-European EuroPrevall project. Multivariable logistic regression was applied to determine associations between the predictor variables and sensitization to foods commonly implicated in food allergy (specific IgE ≥0.35 kUA/L). Secondary outcomes were inhalant sensitization and primary (non-cross-reactive) FS. RESULTS: Dog ownership in early childhood was inversely associated with childhood FS (odds ratio, 0.65; 95% CI, 0.48-0.90), as was higher gestational age at delivery (odds ratio, 0.93 [95% CI, 0.87-0.99] per week increase in age). Lower age and male sex were associated with a higher prevalence of adult FS (odds ratio, 0.97 [95% CI, 0.96-0.98] per year increase in age, and 1.39 [95% CI, 1.12-1.71] for male sex). No statistically significant associations were found between other evaluated environmental determinants and childhood or adult FS, nor between infant diet and childhood FS, although early introduction of solids did show a trend toward prevention of FS. CONCLUSIONS: Dog ownership seems to protect against childhood FS, but independent effects of other currently conceived environmental and infant dietary determinants on FS in childhood or adulthood could not be confirmed.

Incidence trends of airflow obstruction among European adults without asthma: a 20-year cohort study.

Investigating COPD trends may help healthcare providers to forecast future disease burden. We estimated sex- and smoking-specific incidence trends of pre-bronchodilator airflow obstruction (AO) among adults without asthma from 11 European countries within a 20-year follow-up (ECRHS and SAPALDIA cohorts). We also quantified the extent of misclassification in the definition based on pre-bronchodilator spirometry (using post-bronchodilator measurements from a subsample of subjects) and we used this information to estimate the incidence of post-bronchodilator AO (AOpost-BD), which is the primary characteristic of COPD. AO incidence was 4.4 (95% CI: 3.5-5.3) male and 3.8 (3.1-4.6) female cases/1,000/year. Among ever smokers (median pack-years: 20, males; 12, females), AO incidence significantly increased with ageing in men only [incidence rate ratio (IRR), 1-year increase: 1.05 (1.03-1.07)]. A strong exposure-response relationship with smoking was found both in males [IRR, 1-pack-year increase: 1.03 (1.02-1.04)] and females [1.03 (1.02-1.05)]. The positive predictive value of AO for AOpost-BD was 59.1% (52.0-66.2%) in men and 42.6% (35.1-50.1%) in women. AOpost-BD incidence was 2.6 (1.7-3.4) male and 1.6 (1.0-2.2) female cases/1,000/year. AO incidence was considerable in Europe and the sex-specific ageing-related increase among ever smokers was strongly related to cumulative tobacco exposure. AOpost-BD incidence is expected to be half of AO incidence.

Airflow Obstruction and Cardio-metabolic Comorbidities.

Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and often co-exists with cardiovascular disease (CVD), hypertension and diabetes. This international study assessed the association between airflow obstruction and these comorbidities. 23,623 participants (47.5% males, 19.0% current smokers, age: 55.1 ± 10.8 years) in 33 centers in the Burden of Obstructive Lung Disease (BOLD) initiative were included. 10.4% of subjects had airflow obstruction. Self-reports of physician-diagnosed CVD (heart disease or stroke), hypertension and diabetes were regressed against airflow obstruction (post-bronchodilator FEV1/FVC < 5th percentile of reference values), adjusting for age, sex, smoking (including pack-years), body mass index and education. Analyses were undertaken within center and meta-analyzed across centers checking heterogeneity using the I2-statistic. Crude odds ratios for the association with airflow obstruction were 1.42 (95% CI: 1.20-1.69) for CVD, 1.24 (1.02-1.51) for hypertension, and 0.93 (0.76-1.15) for diabetes. After adjustment these were 1.00 (0.86-1.16) (I2:6%) for CVD, 1.14 (0.99-1.31) (I2:53%) for hypertension, and 0.76 (0.64-0.89) (I2:1%) for diabetes with similar results for men and women, smokers and nonsmokers, in richer and poorer centers. Alternatively defining airflow obstruction by FEV1/FVC < 2.5th percentile or 0.70, did not yield significant other results. In conclusion, the associations of CVD and hypertension with airflow obstruction in the general population are largely explained by age and smoking habits. The adjusted risk for diabetes is lower in subjects with airflow obstruction. These findings emphasize the role of common risk factors in explaining the coexistence of cardio-metabolic comorbidities and COPD.

Spirometry in Central Asian Lowlanders and Highlanders, a Population Based Study.

Introduction: The purpose of the study was to establish spirometric reference values for a Central Asian population of highlanders and lowlanders. Methods: Spirometries from a population-based cross-sectional study performed in 2013 in rural areas of Kyrgyzstan were analyzed. Using multivariable linear regression, Global Lung Function Initiative (GLI) equations were fitted separately for men and women, and altitude of residence (700-800 m, 1,900-2,800 m) to data from healthy, never-smoking Kyrgyz adults. The general GLI equation was applied: Predicted value = e a 0 + a 1 ×  ln ( Height ) + a 2 ×  ln ( Age ) + b 1 ×  ln ( Age 100 ) + b 2 ×  ln ( Age 100 ) 2 + b 3 ×  ln ( Age 100 ) 3              + b 4 ×  ln ( Age 100 ) 4 + b 5 ×  ln ( Age 100 ) 5 Results: Of 2,784 screened Kyrgyz, 448 healthy, non-smoking highlanders (379 females) and 505 lowlanders (368 females), aged 18-91 years, were included. Predicted FVC in Kyrgyz fit best with GLI "North-East Asians," predicted FEV1 fit best with GLI "Other/Mixed." Predicted FEV1/FVC was lower than that of all GLI categories. Age- and sex-adjusted mean FVC and FEV1 were higher in highlanders (+0.138l, +0.132l) than in lowlanders (P < 0.001, all comparisons), but FEV1/FVC was similar. Conclusion: We established prediction equations for an adult Central Asian population indicating that FVC is similar to GLI "North-East Asian" and FEV1/FVC is lower than in all other GLI population categories, consistent with a relatively smaller airway caliber. Central Asian highlanders have significantly greater dynamic lung volumes compared to lowlanders, which may be due to environmental and various other effects.

The prevalence of chronic airflow obstruction in three cities in the Nordic-Baltic region.

BACK GROUND: Chronic airflow obstruction (CAO) is the primary characteristic of Chronic obstructive pulmonary disease (COPD) but is also seen in chronic asthma. OBJECTIVE: To compare the prevalence of CAO and possible risk factors between Tartu in Estonia, Reykjavik in Iceland and Uppsala in Sweden. METHODS: All participants underwent spirometry testing of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) before and after bronchodilation. CAO was defined as post-bronchodilator FEV1/FVC below lower limit of normal. Information on respiratory diseases and smoking status, was obtained through questionnaires administered by trained interviewers. RESULTS: 1037 men and 956 women participated in the study. The prevalence of CAO was lower in women in Tartu compared to the other centres (4.9% vs. 13.4 and 8.7% in Reykjavik and Uppsala, respectively, p = 0.002) while no difference was found for men. A similar picture was seen for the proportion of participants that had smoked 10 pack years or more which was much lower in Tartu for women than in Reykjavik and Uppsala, respectively (13.2% vs. 33.7 and 29.2%, p < 0.001). (Fig. 1). Of the participants with CAO the majority (57-67%) did not have a previous diagnosis of asthma or COPD. CONCLUSION: The prevalence of CAO was lower in Estonian women than in women from Iceland and Sweden. The reason for this was probably that the Estonian women had smoked less than the female participants from Iceland and Sweden. The majority of those with CAO do not have a diagnosed lung disease.

Prevalence and burden of chronic bronchitis symptoms: results from the BOLD study.

We studied the prevalence, burden and potential risk factors for chronic bronchitis symptoms in the Burden of Obstructive Lung Disease study.Representative population-based samples of adults aged ≥40 years were selected in participating sites. Participants completed questionnaires and spirometry. Chronic bronchitis symptoms were defined as chronic cough and phlegm on most days for ≥3 months each year for ≥2 years.Data from 24 855 subjects from 33 sites in 29 countries were analysed. There were significant differences in the prevalence of self-reported symptoms meeting our definition of chronic bronchitis across sites, from 10.8% in Lexington (KY, USA), to 0% in Ile-Ife (Nigeria) and Blantyre (Malawi). Older age, less education, current smoking, occupational exposure to fumes, self-reported diagnosis of asthma or lung cancer and family history of chronic lung disease were all associated with increased risk of chronic bronchitis. Chronic bronchitis symptoms were associated with worse lung function, more dyspnoea, increased risk of respiratory exacerbations and reduced quality of life, independent of the presence of other lung diseases.The prevalence of chronic bronchitis symptoms varied widely across the studied sites. Chronic bronchitis symptoms were associated with significant burden both in individuals with chronic airflow obstruction and those with normal lung function.

Female Smokers Are at Greater Risk of Airflow Obstruction Than Male Smokers. UK Biobank.

RATIONALE: The prevalence of chronic obstructive pulmonary disease (COPD) is increasing faster among women than among men. OBJECTIVES: To examine sex differences in the risk of airflow obstruction (a COPD hallmark) in relation to smoking history. METHODS: We analyzed 149,075 women and 100,252 men taking part in the UK Biobank who had provided spirometry measurements and information on smoking. The association of airflow obstruction with smoking characteristics was assessed by sex using regression analysis. The shape of this relationship was examined using restricted cubic splines. MEASUREMENTS AND MAIN RESULTS: The association of airflow obstruction with smoking status was stronger in women (odds ratio for ex-smokers [ORex], 1.44; ORcurrent, 3.45) than in men (ORex, 1.25; ORcurrent, 3.06) (P for interaction = 5.6 × 10-4). In both sexes, the association of airflow obstruction with cigarettes per day, smoking duration, and pack-years did not follow a linear pattern, with the increase in risk at lower doses being steeper among women. For equal doses of exposure, sex differences were present in both ex-smokers and current smokers for cigarettes per day (P for interactionex = 6.0 × 10-8; P for interactioncurrent = 1.1 × 10-5), smoking duration (P for interactionex = 7.9 × 10-4; P for interactioncurrent = 0.004), and pack-years (P for interactionex = 6.6 × 10-18; P for interactioncurrent = 1.3 × 10-6). Overall, those who started smoking before age 18 years were more likely to have airflow obstruction, but a sex difference in this association was not clear. For equal time since quitting, the reduction in risk among women seemed less marked than among men. CONCLUSIONS: Exposed to the same dose of smoking, women showed a higher risk of airflow obstruction than men. This could partly explain the increasingly smaller sex difference in the prevalence of COPD, especially in countries where smoking patterns have become similar between women and men.

Association of pulse wave velocity with total lung capacity: A cross-sectional analysis of the BOLD London study.

BACKGROUND: Low lung function, measured using spirometry, has been associated with mortality from cardiovascular disease, but whether this is explained by airflow obstruction or restriction is a question that remains unanswered. OBJECTIVES: To assess the association of total lung capacity (TLC), forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) with several cardio-metabolic and inflammatory markers. METHODS: In the follow up of the Burden of Lung Disease (BOLD) study in London, acceptable post-bronchodilator spirometric, pulse rate, pulse wave velocity and blood pressure data were obtained from 108 participants. Blood samples for measurement of cardio-metabolic and inflammatory markers were also collected from these participants. Association of lung function and volume with the different biomarkers was examined in multivariable linear regression models adjusted for potential confounders. RESULTS: Following adjustment for age, sex, height, and ethnicity, TLC (adjusted coefficient = -1.53; 95% CI: -2.57, -0.49) and FVC (adjusted coefficient = -2.66; 95% CI: -4.98, -0.34) were inversely associated with pulse wave velocity, and further adjustment for smoking status, pack-years and body mass index (BMI) did not materially change these results. FEV1 was inversely associated with systolic blood pressure, and adjustment for smoking status, pack-years and BMI made this association stronger (adjusted coefficient = -9.47; 95% CI: -15.62, -3.32). CONCLUSION: The inverse association of pulse wave velocity, which is a marker of cardiovascular disease, with TLC suggests that the association of the former with low FVC is independent of airflow obstruction. The association between FEV1 with systolic blood pressure after adjustment for FVC suggests an association with airflow obstruction rather than with restricted spirometry.

Tuberculosis associates with both airflow obstruction and low lung function: BOLD results.

In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. The objective of the present study was to assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults.The study was performed in adults, aged 40 years and above, who took part in the multicentre, cross-sectional, general population-based Burden of Obstructive Lung Disease study, and had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high- and low/middle-income countries, according to gross national income.A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio 2.51, 95% CI 1.83-3.42) and spirometric restriction (adjusted odds ratio 2.13, 95% CI 1.42-3.19).A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common.

Global and regional trends in COPD mortality, 1990-2010.

Between 1990 and 2010, chronic obstructive pulmonary disease (COPD) moved from the fourth to third most common cause of death worldwide. Using data from the Global Burden of Disease programme we quantified regional changes in the number of COPD deaths and COPD mortality rates between 1990 and 2010. We estimated the proportion of the change that was attributable to gross national income per capita and an index of cumulative smoking exposure, and quantified the difference in mortality rates attributable to demographic changes. Despite a substantial decrease in COPD mortality rates, COPD deaths fell only slightly, from three million in 1990 to 2.8 million in 2010, because the mean age of the population increased. The number of COPD deaths in 2010 would have risen to 5.2 million if the age- and sex-specific mortality rates had remained constant. Changes in smoking led to only a small increase in age- and sex-specific mortality rates, which were strongly associated with changes in gross national income. The increased burden of COPD mortality was mainly driven by changes in age distribution, but age- and sex-specific rates fell as incomes rose. The rapid response to increasing affluence suggests that changes in COPD mortality are not entirely explained by changes in early life.

Chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common disease with high global morbidity and mortality. COPD is characterized by poorly reversible airway obstruction, which is confirmed by spirometry, and includes obstruction of the small airways (chronic obstructive bronchiolitis) and emphysema, which lead to air trapping and shortness of breath in response to physical exertion. The most common risk factor for the development of COPD is cigarette smoking, but other environmental factors, such as exposure to indoor air pollutants - especially in developing countries - might influence COPD risk. Not all smokers develop COPD and the reasons for disease susceptibility in these individuals have not been fully elucidated. Although the mechanisms underlying COPD remain poorly understood, the disease is associated with chronic inflammation that is usually corticosteroid resistant. In addition, COPD involves accelerated ageing of the lungs and an abnormal repair mechanism that might be driven by oxidative stress. Acute exacerbations, which are mainly triggered by viral or bacterial infections, are important as they are linked to a poor prognosis. The mainstay of the management of stable disease is the use of inhaled long-acting bronchodilators, whereas corticosteroids are beneficial primarily in patients who have coexisting features of asthma, such as eosinophilic inflammation and more reversibility of airway obstruction. Apart from smoking cessation, no treatments reduce disease progression. More research is needed to better understand disease mechanisms and to develop new treatments that reduce disease activity and progression.

Remembering the forgotten non-communicable diseases.

The forthcoming post-Millennium Development Goals era will bring about new challenges in global health. Low- and middle-income countries will have to contend with a dual burden of infectious and non-communicable diseases (NCDs). Some of these NCDs, such as neoplasms, COPD, cardiovascular diseases and diabetes, cause much health loss worldwide and are already widely recognised as doing so. However, 55% of the global NCD burden arises from other NCDs, which tend to be ignored in terms of premature mortality and quality of life reduction. Here, experts in some of these 'forgotten NCDs' review the clinical impact of these diseases along with the consequences of their ignoring their medical importance, and discuss ways in which they can be given higher global health priority in order to decrease the growing burden of disease and disability.

Gender differences in prevalence, diagnosis and incidence of allergic and non-allergic asthma: a population-based cohort.

BACKGROUND: Although women with severe non-allergic asthma may represent a substantial proportion of adults with asthma in clinical practice, gender differences in the incidence of allergic and non-allergic asthma have been little investigated in the general population. METHODS: Gender differences in asthma prevalence, reported diagnosis and incidence were investigated in 9091 men and women randomly selected from the general population and followed up after 8-10 years as part of the European Community Respiratory Health Survey. The protocol included assessment of bronchial responsiveness, IgE specific to four common allergens and skin tests to nine allergens. RESULTS: Asthma was 20% more frequent in women than in men over the age of 35 years. Possible under-diagnosis of asthma appeared to be particularly frequent among non-atopic individuals, but was as frequent in women as in men. The follow-up of subjects without asthma at baseline showed a higher incidence of asthma in women than in men (HR 1.94; 95% CI 1.40 to 2.68), which was not explained by differences in smoking, obesity or lung function. More than 60% of women and 30% of men with new-onset asthma were non-atopic. The incidence of non-allergic asthma was higher in women than in men throughout all the reproductive years (HR 3.51; 95% CI 2.21 to 5.58), whereas no gender difference was observed for the incidence of allergic asthma. CONCLUSIONS: This study shows that female sex is an independent risk factor for non-allergic asthma, and stresses the need for more careful assessment of possible non-allergic asthma in clinical practice, in men and women.