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1.  Sensitization to airborne allergens among adults and its impact on allergic symptoms: a population survey in northern Vietnam 
The knowledge about allergic sensitization and its relationship with clinical symptoms and diseases among adults in South-East Asia is poor. The aim of this study was to investigate the prevalence and pattern of allergic sensitization and the association with asthma and allergic rhinitis in adults in urban and rural Vietnam.
Among 5,782 responders to a questionnaire survey in northern Vietnam, a random sample was invited to a clinical follow-up and 684 (46%) participated. The methods included a structured interview using a modified GA2LEN study questionnaire on symptoms and possible determinants for diseases. Skin prick test (SPT) with ten common airborne indoor and outdoor allergens, lung function test, and methacholine test was performed among subjects ≤60 years of age.
In total, one third of subjects had a positive SPT reaction to at least one allergen, 36.9% of men and 31.0% of women (n.s.). The most common sensitizer was the storage mite B. tropicalis (men 27.7%; women 18.7%) followed by house dust mite D. pteronyssinus (men 16.5%; women 10.6%), and D. farinae (men 15.3%; women 6.3%), and cockroach (men 16.5%; women 10.2%). Sensitization to all major allergens were significantly more common among men and among subjects ≤45 years compared with women and subjects >45 years, respectively. The prevalence of sensitization to animals, pollen and molds were low. The majority of cockroach-sensitized subjects were also sensitized to mites. Sensitization to any allergen and all major allergens were significantly associated with rhinitis, but not with asthma. However, bronchial hyper-reactivity was significantly associated with increasing number of positive SPTs (p = 0.047).
Among adults in northern Vietnam sensitization to mite and cockroach most common in both rural and urban areas. The dominant sensitizer was the storage mite B. tropicalis, which should be included in future studies and also in clinical practice, owing to its association with clinical symptoms. As in the Western world allergic sensitization was associated with rhinitis and bronchial hyper-reactivity. The lack of association with asthma in South-East Asia needs to be studied further.
PMCID: PMC3923743  PMID: 24512828
Allergic sensitization; Asthma; Allergic rhinitis; Storage mite; Vietnam
2.  Prevalence trends in respiratory symptoms and asthma in relation to smoking - two cross-sectional studies ten years apart among adults in northern Sweden 
Smoking is considered to be the single most important preventable risk factor for respiratory symptoms. Estimating prevalence of respiratory symptoms is important since they most often precede a diagnosis of an obstructive airway disease, which places a major burden on the society. The aim of this study was to estimate prevalence trends of respiratory symptoms and asthma among Swedish adults, in relation to smoking habits. A further aim was to estimate the proportion of respiratory symptom and asthma prevalence attributable to smoking.
Data from two large-scale cross-sectional surveys among adults performed in northern Sweden in 1996 and 2006 were analysed. Identical methods and the same questionnaire were used in both surveys. The association between smoking, respiratory symptoms and asthma was analysed with multiple logistic regression analyses. Changes in prevalence of respiratory symptoms and asthma from 1996 to 2006 were expressed as odds ratios. Additionally, the population attributable risks of smoking were estimated.
The prevalence of most respiratory symptoms decreased significantly from 1996 to 2006. Longstanding cough decreased from 12.4 to 10.1%, sputum production from 19.0 to 15.0%, chronic productive cough from 7.3 to 6.2%, and recurrent wheeze from 13.4 to 12.0%. Any wheeze and asthmatic wheeze remained unchanged. This parallels to a decrease in smoking from 27.4 to 19.1%. In contrast, physician-diagnosed asthma increased from 9.4 to 11.6%. The patterns were similar after correction for confounders. All respiratory symptoms were highly associated with smoking, and the proportion of respiratory symptoms in the population attributed to smoking (PAR) ranged from 9.8 to 25.5%. In 2006, PAR of smoking was highest for recurrent wheeze (20.6%).
In conclusion, we found that respiratory symptoms, in particular symptoms common in bronchitis, decreased among adults in northern Sweden, parallel to a decrease in smoking from 1996 to 2006. In contrast, the prevalence of physician-diagnosed asthma increased during the same time-period. Up to one fourth of the respiratory symptom prevalence in the population was attributable to smoking.
PMCID: PMC3929247  PMID: 24383710
Respiratory symptoms; Asthma; Prevalence; Smoking; Attributable risk; Trends
3.  Increase in sensitization to common airborne allergens among adults – two population-based studies 15 years apart 
Studies on time trends of allergic sensitization among adults are rare. The aim of the study was to compare the prevalence of allergic sensitization to common airborne allergens among adults 15 years apart and to identify risk factors for allergic sensitization.
Clinical examinations including skin prick test (SPT) and structured interviews were performed in two random population samples in 1994 and 2009. Furthermore, specific IgE was analyzed in 2009. SPT data were available for 483 subjects in 1994 and for 463 subjects in 2009 in ages 20–60 years. Specific IgE was analyzed in 692 subjects in ages 20–79 years.
Sensitization to cat (16% to 26%, p < 0.001), dog (13% to 25%, p < 0.001), birch (13% to 18%, p = 0.031) and timothy (12% to 21%, p < 0.001), based on SPT, increased significantly from 1994 to 2009. Sensitization to any positive SPT increased from 35% to 39%, p = 0.13.The proportion of having ≥3 positive SPT reactions increased from 40% to 56%, p = 0.002. The sensitization pattern yielded similar results based on specific IgE. Risk factors for allergic sensitization were having a family history of allergy (OR 3.1, 95% CI 2.0-4.8 for any positive SPT; OR 2.7, 95% CI 1.8-4.0 for any elevated IgE) and urban living (OR 1.7, 95% CI 1.0-2.7; OR 1.5, 95% CI 1.0-2.4).
The prevalence of allergic sensitization to major airborne allergens as well as multi-sensitization increased significantly between the study years. Young age, a family history of allergy and urban living were significant risk factors for allergic sensitization.
PMCID: PMC3684537  PMID: 23758681
Allergic sensitization; Epidemiology; IgE; Population study; Prevalence; Skin prick test
5.  Galactose-α-1,3-Galactose–Specific IgE Is Associated with Anaphylaxis but Not Asthma 
Rationale: IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract.
Objectives: To evaluate the relationship between IgE antibodies to α-gal and asthma, and compare this with the relationship between asthma and IgE antibodies to Fel d 1 and other protein allergens.
Methods: Patients being investigated for recurrent anaphylaxis, angioedema, or acute urticaria underwent spirometry, exhaled nitric oxide, questionnaires, and serum IgE antibody assays. The results were compared with control subjects and cohorts from the emergency department in Virginia (n = 130), northern Sweden (n = 963), and rural Kenya (n = 131).
Measurements and Main Results: Patients in Virginia with high-titer IgE antibodies to α-gal had normal lung function, low levels of exhaled nitric oxide, and low prevalence of asthma symptoms. Among patients in the emergency department and children in Kenya, there was no association between IgE antibodies to α-gal and asthma (odds ratios, 1.04 and 0.75, respectively). In Sweden, IgE antibodies to cat were closely correlated with IgE antibodies to Fel d 1 (r = 0.83) and to asthma (P < 0.001).
Conclusions: These results provide a model of an ectoparasite-induced specific IgE response that can increase total serum IgE without creating a risk for asthma, and further evidence that the main allergens that are causally related to asthma are those that are inhaled.
PMCID: PMC3326422  PMID: 22281828
α-gal; red meat allergy; ticks; total serum IgE; ectoparasite
6.  A Strong Synergism of Low Birth Weight and Prenatal Smoking on Asthma in Schoolchildren 
Pediatrics  2011;127(4):e905-e912.
Prenatal smoke exposure is associated with airway inflammation and asthma in children. It also increases the risk of low birth weight (LBW). LBW is associated with decreased lung function independently of smoking.
To study the independent and joint effects of prenatal smoking and LBW on childhood asthma.
In 1996, all children aged 7 to 8 years in 3 cities in northern Sweden were invited to an International Study of Asthma and Allergy in Childhood questionnaire survey. This study focused on the follow-up of children aged 11 to 12 years, in which 3389 children (96%) participated. A subset of 2121 children underwent skin-prick testing. Self-reported physician-diagnosed asthma has been clinically validated.
Mean birth weight was 3360 g in children exposed to prenatal smoking and 3571 g in nonexposed children (P < .001). The association of prenatal smoking with physician-diagnosed asthma was stronger in LBW children (risk ratio: 8.8 [95% confidence interval: 2.1–38]) than in normal birth weight children (risk ratio: 1.3 [95% confidence interval: 1.0–1.8]). LBW alone was not an independent predictor of asthma. These associations were similar in multivariate analysis, and the interaction term LBW × smoking was highly statistically significant.
There was a strong interaction of LBW and prenatalsmoking on the risk of physician-diagnosed asthma, which has not been demonstrated previously. This was consistently seen with adjustment for known risk factors, including allergic sensitization. Plausibly, airway inflammation from prenatal smoke exposure induces obstructive symptoms more easily in the underdeveloped airways of LBW children.
PMCID: PMC3387890  PMID: 21422092
wheeze; child; prevalence; epidemiology; risk
7.  Up-to-date on mortality in COPD - report from the OLIN COPD study 
The poor recognition and related underdiagnosis of COPD contributes to an underestimation of mortality in subjects with COPD. Data derived from population studies can advance our understanding of the true burden of COPD. The objective of this report was to evaluate the impact of COPD on mortality and its predictors in a cohort of subjects with and without COPD recruited during the twenty first century.
All subjects with COPD (n = 993) defined according to the GOLD spirometric criteria, FEV1/FVC < 0.70, and gender- and age-matched subjects without airway obstruction, non-COPD (n = 993), were identified in a clinical follow-up survey of the Obstructive Lung Disease in Northern Sweden (OLIN) Studies cohorts in 2002-2004. Mortality was observed until the end of year 2007. Baseline data from examination at recruitment were used in the risk factor analyses; age, smoking status, lung function (FEV1 % predicted) and reported heart disease.
The mortality was significantly higher among subjects with COPD, 10.9%, compared to subjects without COPD, 5.8% (p < 0.001). Mortality was associated with higher age, being a current smoker, male gender, and COPD. Replacing COPD with FEV1 % predicted in the multivariate model resulted in the decreasing level of FEV1 being a significant risk factor for death, while heart disease was not a significant risk factor for death in any of the models.
In this cohort COPD and decreased FEV1 were significant risk factors for death when adjusted for age, gender, smoking habits and reported heart disease.
PMCID: PMC3276412  PMID: 22230685
8.  Conventional epidemiology underestimates the incidence of asthma and wheeze-a longitudinal population-based study among teenagers 
Because of shifts in the gender ratio and incidence and remission rates of asthma during the teen ages, the methodology of incidence studies among teenagers is important, i.e. if the time intervals between surveys are too long, the incident cases might not be properly identified. The aim was to study the impact of study design on the incidence rates of asthma and wheeze during the teen ages.
In a study about asthma and allergic diseases within the OLIN studies (Obstructive Lung Disease in northern Sweden), a cohort of school children (n = 3,430) was followed annually by questionnaire from age 8 yrs. In the endpoint survey (age 18 yrs) 2,582 (75% of original responders) participated. Incident cases from age 12-18 yrs were identified by two methods: annual questionnaire reports (AR) and baseline-endpoint surveys only (BE).
The cumulative incidence of asthma and wheeze was significantly higher based on AR compared to BE. Compared to the incidence rates based on all the annual surveys, the calculated average annual rates based on BE were in general lower both among the boys and among the girls. There were no differences between boys and girls in incidence rates of asthma or wheeze during the early teen years. However, from the age of 15 years, the annual incidence rates were significantly or borderline significantly higher among girls than boys. At onset, the additional cases of current asthma identified by AR had significantly less severe asthma than those identified in BE (p < 0.02).
the size of the incidence of asthma and wheeze during the teen ages was influenced by study design. By using the conventional prospective study design with longer follow-up time, the incidence was underestimated.
PMCID: PMC3395824  PMID: 22409857
asthma; adolescents; epidemiology; incidence; study design; wheezing
9.  Heavy vehicle traffic is related to wheeze among schoolchildren: a population-based study in an area with low traffic flows 
Environmental Health  2011;10:91.
An association between traffic air pollution and respiratory symptoms among children has been reported. However, the effects of traffic air pollution on asthma and wheeze have been very sparsely studied in areas with low traffic intensity in cold climate with poor dispersion. We evaluated the impact of vehicle traffic on childhood asthma and wheeze by objective exposure assessment.
As a part of the Obstructive Lung Disease in Northern Sweden (OLIN) studies, a questionnaire was sent to the families of all children attending first or second grade in Luleå (72,000 inhabitants) in Northern Sweden in 2006. The age of the children was 7-8 years and the participation rate was 98% (n = 1357). Skin prick tests were performed in 1224 (89%) children. The home addresses were given geographical coordinates and traffic counts were obtained from the local traffic authorities. A proximity model of average daily traffic and average daily heavy vehicle traffic within 200 meters from each participant's home address was used. The associations between traffic exposure and asthma and wheeze, respectively, were analysed in an adjusted multiple logistic regression model.
Exposure to high traffic flows was uncommon in the study area; only 15% of the children lived within 200 meters from a road with a traffic flow of ≥8000 vehicles per day. Living closer than 200 meters from a road with ≥500 heavy vehicles daily was associated with current wheeze, odds ratio 1.7 (confidence interval 1.0-2.7). A dose-response relation was indicated. An increased risk of asthma was also seen, however not significant, odds ratio 1.5 (confidence interval 0.8-2.9). Stratified analyses revealed that the effect of traffic exposure was restricted to the non-sensitized phenotype of asthma and wheeze. The agreement between self-reported traffic exposure and objective measurements of exposure was moderate.
This study showed that already at low levels of exposure, vehicle traffic is related to an increased risk of wheeze among children. Thus, the global burden of traffic air pollution may be underestimated.
PMCID: PMC3206415  PMID: 21995638
10.  Allergic rhinitis in northern vietnam: increased risk of urban living according to a large population survey 
Little is known about prevalence and risk factors of allergic rhinitis and chronic nasal symptoms among adults in Vietnam. We aimed to estimate the prevalence, risk factor patterns and co-morbidities of allergic rhinitis and chronic nasal symptoms in one urban and one rural area in northern Vietnam.
A cross-sectional questionnaire survey was conducted from August 2007 to January 2008 in urban Hoankiem and rural Bavi in Hanoi among adults aged 21-70 years. Of 7008 randomly selected subjects, 91.7% participated in Bavi and 70.3% in Hoankiem.
Allergic rhinitis ever or chronic nasal symptoms were reported by 50.2%. The prevalence of allergic rhinitis ever was considerably higher in Hoankiem compared to Bavi, 29.6% vs 10.0% (p < 0.001). Allergic rhinitis ever and chronic nasal symptoms were both significantly associated with asthma and respiratory symptoms, respectively (p < 0.001). Exposure to gas, dust or fumes at work was significantly associated with allergic rhinitis ever, OR 1.57 (95% CI 1.34 - 1.84), nasal blocking, OR 1.90 (95% CI 1.68 - 2.15) and runny nose, OR 1.32 (95% CI 1.17 - 1.49), while somewhat surprisingly no association with smoking was found. Female sex was a significant risk factor for both nasal blocking and runny nose.
Allergic rhinitis ever was considerably more common in the urban area. Nasal blocking and runny nose was each reported by about one third of the studied sample with no major urban-rural difference. Further, exposure to air pollution at work was significantly associated with allergic rhinitis ever, nasal blocking and runny nose.
PMCID: PMC3339357  PMID: 22410330
Allergic rhinitis; nasal blocking; runny nose/chronic rhinitis; epidemiology; Vietnam
11.  Major increase in allergic sensitization in school children from 1996 to 2006 in Northern Sweden 
Time trends for allergic sensitization are poorly known.
To compare the trends in prevalence of allergic sensitization and associated risk factors in children.
Two cohorts of children (age 7–8 years) were invited to skin prick testing (SPT) ten years apart, 1996 and 2006. Participation rate was 2148 (88%) and 1700 (90%), respectively. The methods were identical and ten common airborne allergens were used. An expanded ISAAC-questionnaire about symptoms and possible risk factors for allergic conditions was completed by the parents.
The prevalence of any positive SPT increased from 21% in 1996 to 30% in 2006 (p<0.001). The pattern of sensitization remained similar, and sensitization to cat was most common both years, 13% and 19%, respectively. Sensitization to mites and mould were uncommon in both surveys. A family history of allergy was a significant risk factor for a positive SPT both years (OR 1.7). Factors that in 1996 had a protective effect, i.e. rural living and having several siblings, had lost this effect in 2006. The prevalence of most risk factors remained similar, but respiratory infections and smoking among parents decreased significantly. During the same period there was no significant increase in prevalence of current wheeze (11.9% to 12.4%, n.s.) or symptoms of rhinitis or eczema.
The prevalence of allergic sensitization increased significantly from 1996 to 2006, while no increase in clinical symptoms was found. The parallel decrease in parental smoking and respiratory infections indicate a different influence of environmental factors on allergic sensitization and clinical symptoms, respectively.
PMCID: PMC2747664  PMID: 19577282
allergic sensitization; atopic disease; epidemiology; OLIN; school children; skin prick test
12.  West Sweden Asthma Study: Prevalence trends over the last 18 years argues no recent increase in asthma 
Respiratory Research  2009;10(1):94.
Asthma prevalence has increased over the last fifty years, but the more recent changes have not been conclusively determined. Studies in children indicate that a plateau in the prevalence of asthma may have been reached, but this has not yet been confirmed in adults. Epidemiological studies have suggested that the prevalence of asthma in adults is approximately 7-10% in different parts of the western world.
We have now performed a large-scale epidemiological evaluation of the prevalence of asthma and respiratory symptoms in adults between the ages of 16-75 in West Sweden. Thirty thousand randomly chosen individuals were sent a detailed questionnaire focusing on asthma and respiratory symptoms, as well possible risk factors. Sixty-two percent of the contacted individuals responded to the questionnaire. Asthma prevalence, defined as asthma diagnosed by a physician, was 8.3%. Moreover, the prevalence of respiratory symptoms was lower compared to previous studies. The most common respiratory symptom was any wheeze (16.6%) followed by sputum production (13.3%). In comparison with studies performed 18 years ago, the prevalence of asthma has not increased, and the prevalence of most respiratory symptoms has decreased. Therefore, our data argues that the continued increase in asthma prevalence that has been observed over the last half century is over.
PMCID: PMC2772988  PMID: 19821983
13.  Health-related quality of life is related to COPD disease severity 
The aim of this study was to evaluate the association between health-related quality of life (HRQL) and disease severity using lung function measures.
A survey was performed in subjects with COPD in Sweden. 168 subjects (70 women, mean age 64.3 years) completed the generic HRQL questionnaire, the Short Form 36 (SF-36), the disease-specific HRQL questionnaire; the St George's Respiratory Questionnaire (SGRQ), and the utility measure, the EQ-5D. The subjects were divided into four severity groups according to FEV1 per cent of predicted normal using two clinical guidelines: GOLD and BTS. Age, gender, smoking status and socio-economic group were regarded as confounders.
The COPD severity grades affected the SGRQ Total scores, varying from 25 to 53 (GOLD p = 0.0005) and from 25 to 45 (BTS p = 0.0023). The scores for SF-36 Physical were significantly associated with COPD severity (GOLD p = 0.0059, BTS p = 0.032). No significant association were noticed for the SF-36, Mental Component Summary scores and COPD severity. Scores for EQ-5D VAS varied from 73 to 37 (GOLD I-IV p = 0.0001) and from 73 to 50 (BTS 0-III p = 0.0007). The SGRQ Total score was significant between age groups (p = 0.0047). No significant differences in HRQL with regard to gender, smoking status or socio-economic group were noticed.
The results show that HRQL in COPD deteriorates with disease severity and with age. These data show a relationship between HRQL and disease severity obtained by lung function.
PMCID: PMC1215504  PMID: 16153294
Health-related quality of life; COPD; disease severity; epidemiological, Global Initiative for Chronic Obstructive Lung Disease (GOLD); St George's Respiratory Questionnaire (SGRQ)
14.  Questionnaire layout and wording influence prevalence and risk estimates of respiratory symptoms in a population cohort 
Results of epidemiological studies are greatly influenced by the chosen methodology. The study aims to investigate how two frequently used questionnaires (Qs), with partly different layout, influence the prevalence of respiratory symptoms.
Study Design and Setting
A booklet containing two Qs, the Global Allergy and Asthma European Network Q and the Obstructive Lung Disease in Northern Sweden Q, was mailed to 30 000 subjects aged 16–75 years in West Sweden; 62% responded. Sixteen questions were included in the analysis: seven identical between the Qs, four different in set-up and five with the same layout but different wording. Comparisons were made using differences in proportions, observed agreement and Kappa statistics.
Identical questions yielded similar prevalences with high observed agreement and kappa values. Questions with different set-up or differences in wording resulted in significantly different prevalences with lower observed agreement and kappa values. In general, the use of follow-up questions, excluding subjects answering no to the initial question, resulted in 2.9–6.7% units lower prevalence.
The question set-up has great influences on epidemiological results, and specifically questions that are set up to be excluded based on a previous no answer leads to lower prevalence compared with detached questions. Therefore, Q layout and exact wording of questions has to be carefully considered when comparing studies.
Please cite this paper as: Ekerljung L, Rönmark E, Lötvall J, Wennergren G, Torén K and Lundbäck B. Questionnaire layout and wording influence prevalence and risk estimates of respiratory symptoms in a population cohort. Clin Respir J 2013; 7: 53–63.
PMCID: PMC3654566  PMID: 22243692
epidemiology; GA2LEN; kappa; OLIN; questionnaire; respiratory symptoms

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