Ulf Nihlén

Traffic-related air pollution associated with prevalence of asthma and COPD/chronic bronchitis. A cross-sectional study in Southern Sweden

BackgroundThere is growing evidence that air pollution from traffic has adverse long-term effects on chronic respiratory disease in children, but there are few studies and more inconclusive results in adults. We examined associations between residential traffic and asthma and COPD in adults in southern Sweden. A postal questionnaire in 2000 (n = 9319, 18–77 years) provided disease status, and self-reported exposure to traffic. A Geographical Information System (GIS) was used to link geocoded residential addresses to a Swedish road database and an emission database for NOx.ResultsLiving within 100 m of a road with >10 cars/minute (compared with having no heavy road within this distance) was associated with prevalence of asthma diagnosis (OR = 1.40, 95% CI = 1.04–1.89), and COPD diagnosis (OR = 1.64, 95%CI = 1.11–2.4), as well as asthma and chronic bronchitis symptoms. Self-reported traffic exposure was associated with asthma diagnosis and COPD diagnosis, and with asthma symptoms. Annual average NOx was associated with COPD diagnosis and symptoms of asthma and chronic bronchitis.ConclusionLiving close to traffic was associated with prevalence of asthma diagnosis, COPD diagnosis, and symptoms of asthma and bronchitis. This indicates that traffic-related air pollution has both long-term and short-term effects on chronic respiratory disease in adults, even in a region with overall low levels of air pollution.

Prevalence of hand eczema in an adult Swedish population and the relationship to risk occupation and smoking

Using a postal questionnaire the prevalence of hand eczema was determined in a general population of 11,798 individuals aged 20-77 years who were randomly drawn from the population records. The response rate was 78.1%. One-year prevalence of hand eczema among women varied between 1.9% and 10.8%, with the highest figure among those aged 30-39 years. The corresponding figures for men were 2.3% and 5.6%, with the highest figure among those aged 20-29 years. Lifetime prevalence varied between 5.7% and 16.7% among women and between 5.2% and 9.5% among men. Using multiple logistic regression analysis female sex (OR=1.91, 95% CI 1.47-2.47) and smoking (OR=1.35, 95% CI 1.04-1.75) were independent risk factors for reporting 1-year prevalence of hand eczema, whereas age (OR=0.99, 95% CI 0.97-0.99) was inversely related to the 1-year prevalence of hand eczema. Aggregated risk occupation or categorized occupation such as medical and nursing work, production or service were not significantly associated with 1-year prevalence of hand eczema.

Traffic exposure associated with allergic asthma and allergic rhinitis in adults. A cross-sectional study in southern Sweden

BackgroundThere is conflicting evidence that traffic-related air pollution is a risk factor for allergic conditions. Few studies have investigated this in adults. In adults, a high proportion of asthma, rhinitis and eczema is triggered by non-allergic factors. We investigated traffic as a risk factor for allergic versus non-allergic asthma and rhinitis, and eczema, in adults.A questionnaire from 2000 (n = 9319, 18–77 years) provided individual data about disease outcome and self-reported traffic exposure. Additional exposure assessments were obtained using Geographical Informations Systems (GIS). Residential addresses were linked to the national Swedish Road Database and to a pollutant database with modelled annual means of NOx (Nitrogen Oxids).ResultsLiving within 100 m from a road with a traffic intensity of >10 cars/min (24 hour mean) was associated with prevalence of current asthma reported to be triggered by allergic factors (OR = 1.83, 95% CI = 1.23–2.72) and with allergic rhinitis (OR = 1.30, 95%CI = (1.05–1.61). No relation was seen with asthma or rhinitis triggered by other factors. Living within 100 m of a road with >10 cars/min was also associated with hand-eczema during the last 12 months (OR = 1.63, 95% CI = 1.19–2.23), but not with allergic eczema or diagnosed hand-eczema. Consistent results were seen using self-reported traffic, but the associations with NOx were less consistent.ConclusionExposure to traffic was associated with a higher prevalence of allergic asthma and allergic rhinitis, but not with asthma or rhinitis triggered by non-allergic factors. This difference was suggested by the overall pattern, but only clear using GIS-measured traffic intensity as a proxy for traffic exposure. An association was also found with hand-eczema during the last 12 months. We suggest that asthma and rhinitis should not be treated as homogenous groups when estimating effects from traffic in adults.

Incidence and remission of self-reported allergic rhinitis symptoms in adults.

Background:  A few studies have examined the incidence and remission of allergic rhinitis (AR) in the same general population.

Total desmosines in plasma and urine correlate with lung function

The aim of the present study was to evaluate the relationship between the matrix degradation biomarkers, desmosine and isodesmosine (desmosines), and lung function. Plasma and creatinine-corrected urinary total desmosines (P- and U-desmosines, respectively), lung function and diffusing capacity of the lung for carbon monoxide (DL,CO) were measured in a cohort of subjects from the Swedish Twin Registry. Concentrations of U- and P-desmosines were measured in 349 and 318 subjects, respectively; approximately one-third of subjects had chronic obstructive pulmonary disease (COPD). Age, female sex, body mass index (BMI) and smoking were significantly associated with U-desmosines in a multiple linear regression analysis. In the overall population, after adjustments for age, sex, height, BMI and smoking, concentrations of U-desmosines were significantly correlated with all lung function measures, and P-desmosines with forced expiratory volume in 1 s and DL,CO (p<0.05). With the exception of residual volume versus P-desmosines, relationships between concentrations of desmosines and lung function measures were markedly stronger in subjects with COPD compared with those without COPD. These cross-sectional data showing associations between desmosines and several lung function variables suggest that desmosines, particularly U-desmosines, could be a useful biomarker of COPD status.

Prevalence of self-reported eczema in relation to living environment, socio-economic status and respiratory symptoms assessed in a questionnaire study

BackgroundPotential links between eczema and obstructive pulmonary diseases have been postulated. Previously we have reported the prevalence of upper and lower respiratory diseases and the relation to environmental and socio-economic factors in a randomly selected adult population in southern Sweden using a postal questionnaire.In the present study we wanted to analyse the prevalence of eczema and its relation to socio-economic status, heredity factors and environmental factors in an adult population.MethodsSelf-reported eczema, upper and lower respiratory symptoms, asthma and Chronic Bronchitis Emphysema (CBE) were examined in 12,071 adults, aged 20–59 years, living in southern Sweden by using a postal questionnaire. There were comparable numbers of males and females in all age groups.Multiple logistic regression analysis (forward conditional) was applied to estimate the association between the proposed risk factors (heredity, self-reported asthma and CBE, nasal symptoms, socio-economic group, environmental factors, age, gender and smoking habits) and self-reported eczema.ResultsThe response rate was 70.1%. In all, 1240 subjects (14.6%) stated that they had eczema. In all age cohorts self-reported eczema was more frequently reported by women than by men (p < 0.05). The prevalence of self-reported eczema among the economically active population varied from 17.1% to 8.2% with the highest rates among assistant non-manual employees. However, when controlling for age, gender and risk occupation there was no association between low social position and eczema. Living close to heavy traffic (OR = 1.45, 95% CI 1.25–1.67) and living seaside (OR = 1.17, 95% CI 1.01–1.35) but not urban/suburban living was associated with eczema. Heredity of eczema (OR = 5.77, 95% CI 5.02–6.64), self reported allergic rhinitis (OR = 2.31, 95% CI 2.00–2.68), self reported asthma (OR = 1.98, 95% CI 1.56–2.51) and self reported CBE (OR = 1.42, 95% CI 1.08–1.87) were all associated with eczema.ConclusionsIn this epidemiological study we see that self-reported eczema is a common disease in an adult population especially among women. Eczema seems to be linked to environment factors, obstructive pulmonary diseases and rhinitis.

Impulse oscillometry may be of value in detecting early manifestations of COPD

BACKGROUND Spirometry is used to diagnose chronic obstructive pulmonary disease (COPD). The Impulse oscillometry system (IOS) allows determination of respiratory impedance indices, which might be of potential value in early COPD, although previous experience is limited. We examined pulmonary resistance and reactance measured by IOS in subjects with or without self-reported chronic bronchitis or emphysema or COPD (Q+ or Q-) and subjects with or without COPD diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (G+ or G-). METHODS From a previous population-based study 450 subjects were examined with spirometry and IOS and answered a questionnaire on respiratory symptoms and diseases. RESULTS Seventy-seven subjects were Q+, of whom 34 also were G+. Q+/G- subjects (n = 43) reported respiratory symptoms more frequently (35-40% vs 8-14%) but had higher FEV(1) (100% vs 87%) than Q-/G+ subjects (n = 90), p < 0.05 for both comparisons. Q+ subjects had higher pulmonary resistance and lower pulmonary reactance than Q- subjects (p < 0.01 for all comparisons). The same pattern was seen both in G+ subjects ((Q+/Q-) R5 0.39/0.32, R5-R20 0.10/0.07, X5 0.13/0.09, AX 0.55/0.27, p < 0.05 for all) and G- subjects ((Q+/Q-) R5 0.35/0.29, R5-R20 0.08/0.06, X5 0.10/0.08, AX 0.31/0.19 p < 0.05 for all) except for R20 (adjusted for gender and age). CONCLUSIONS Self-reported chronic bronchitis or emphysema or COPD was associated with higher pulmonary resistance and lower pulmonary reactance measured by IOS, both among subjects with and without COPD according to GOLD criteria. IOS may have the potential to detect pathology associated with COPD earlier than spirometry.

Budesonide added to formoterol contributes to improved exercise tolerance in patients with COPD

BACKGROUND Breathlessness and exercise intolerance frequently impact the daily life of patients with COPD. METHODS This double-blind, multicentre, three-period crossover study randomised 111 patients with COPD (mean age 64 years, mean FEV(1) 38% of predicted normal) to budesonide/formoterol 320/9 microg, formoterol 9 microg or placebo, twice daily for 1 week, following a 1-week run-in period with 1-week wash-out between treatments. Terbutaline (0.5 mg/dose) was used as needed. The primary efficacy variable was exercise endurance time (EET) at 75% peak work capacity with cycle ergometry assessed 1 h post-morning dose. RESULTS Budesonide/formoterol prolonged EET 1 h post-morning dose versus formoterol by 69 s (P < 0.005) and placebo by 105 s (P < 0.0001) and improved inspiratory capacity (IC) at isotime during exercise versus formoterol by 8% (P = 0.011) and placebo by 16% (P < 0.0001). Borg score at isotime was reduced by 0.48 (P = 0.12) and 0.78 (P = 0.014) compared with formoterol and placebo, respectively. At the repeated cycle test 6 h after morning dose, the effect on EET still favoured budesonide/formoterol over formoterol and placebo, while the isotime IC and Borg score were similar but better than placebo for the active study drugs. Budesonide/formoterol and formoterol improved health status (St Georges Respiratory Questionnaire total score: mean difference versus placebo -2.4 and -2.2, respectively). All treatments were well tolerated. CONCLUSIONS Budesonide/formoterol resulted in a significant improvement in endurance time 1 h after the last morning dose in a 1-week treatment period versus formoterol and placebo. This study demonstrates, for the first time, the benefit of inhaled corticosteroids in addition to long-acting beta(2)-agonists on exercise tolerance in COPD patients. www.clinicaltrials.gov registration number: NCT00489853.

Increased serum levels of carbohydrate-deficient transferrin in patients with chronic obstructive pulmonary disease

Objective: The reason that only a minority of smokers develop chronic obstructive pulmonary disease (COPD) is still largely unknown. Glycosylation defects are involved in the pathological mechanisms in cystic fibrosis (CF), where chronic progressive obstructive lung disease dominates the clinical picture. Whether defects of protein glycosylation occur in COPD has not previously been examined. Increase in carbohydrate-deficient transferrin (CDT) in serum seems to function as an indicator of general defects of N-glycosylation. Recently, one study observed high serum CDT concentrations in CF patients. We examined whether subjects with COPD also have increased serum CDT levels. Method and results: A total of 131 randomly selected individuals, 45-64 years of age, underwent a medical examination, spirometry and blood tests. Serum CDT was determined using high performance liquid chromatography. In subjects diagnosed as having COPD (n = 15), multiple logistic regression analyses demonstrated a significant relationship between the diagnosis of COPD and CDT, even after all efforts were made to take the influence of age and smoking into account (odds ratio 3.16, 95% CI 1.11-8.95). Also, in subjects with COPD there was an inverse partial correlation between forced expiratory volume in 1 s (FEV1) and serum CDT (r =- 0.81, p = 0.001). Conclusion: These results suggest that protein glycosylation defects occur in COPD and, in addition, might be involved in the pathogenetic mechanisms of the disease. It seems that further investigation of the protein glycosylation in COPD is warranted.OBJECTIVE The reason that only a minority of smokers develop chronic obstructive pulmonary disease (COPD) is still largely unknown. Glycosylation defects are involved in the pathological mechanisms in cystic fibrosis (CF), where chronic progressive obstructive lung disease dominates the clinical picture. Whether defects of protein glycosylation occur in COPD has not previously been examined. Increase in carbohydrate-deficient transferrin (CDT) in serum seems to function as an indicator of general defects of N-glycosylation. Recently, one study observed high serum CDT concentrations in CF patients. We examined whether subjects with COPD also have increased serum CDT levels. METHOD AND RESULTS A total of 131 randomly selected individuals, 45-64 years of age, underwent a medical examination, spirometry and blood tests. Serum CDT was determined using high performance liquid chromatography. In subjects diagnosed as having COPD (n = 15), multiple logistic regression analyses demonstrated a significant relationship between the diagnosis of COPD and CDT, even after all efforts were made to take the influence of age and smoking into account (odds ratio 3.16, 95% CI 1.11-8.95). Also, in subjects with COPD there was an inverse partial correlation between forced expiratory volume in 1 s (FEV1) and serum CDT (r = -0.81, p = 0.001). CONCLUSION These results suggest that protein glycosylation defects occur in COPD and, in addition, might be involved in the pathogenetic mechanisms of the disease. It seems that further investigation of the protein glycosylation in COPD is warranted.

Genetic and environmental influence on lung function impairment in Swedish twins

BackgroundThe understanding of the influence of smoking and sex on lung function and symptoms is important for understanding diseases such as COPD. The influence of both genes and environment on lung function, smoking behaviour and the presence of respiratory symptoms has previously been demonstrated for each of these separately. Hence, smoking can influence lung function by co-varying not only as an environmental factor, but also by shared genetic pathways. Therefore, the objective was to evaluate heritability for different aspects of lung function, and to investigate how the estimates are affected by adjustments for smoking and respiratory symptoms.MethodsThe current study is based on a selected sample of adult twins from the Swedish Twin Registry. Pairs were selected based on background data on smoking and respiratory symptoms collected by telephone interview. Lung function was measured as FEV1, VC and DLco. Pack years were quantified, and quantitative genetic analysis was performed on lung function data adjusting stepwise for sex, pack years and respiratory symptoms.ResultsFully adjusted heritability for VC was 59% and did not differ by sex, with smoking and symptoms explaining only a small part of the total variance. Heritabilities for FEV1 and DLco were sex specific. Fully adjusted estimates were10 and 15% in men and 46% and 39% in women, respectively. Adjustment for smoking and respiratory symptoms altered the estimates differently in men and women. For FEV1 and DLco, the variance explained by smoking and symptoms was larger in men. Further, smoking and symptoms explained genetic variance in women, but was primarily associated with shared environmental effects in men.ConclusionDifferences between men and women were found in how smoking and symptoms influence the variation in lung function. Pulmonary gas transfer variation related to the menstrual cycle has been shown before, and the findings regarding DLco in the present study indicates gender specific environmental susceptibility not shown before. As a consequence the results suggest that patients with lung diseases such as COPD could benefit from interventions that are sex specific.