Increase in pollen sensitization in Swedish adults and protective effect of keeping animals in childhood.

BACKGROUND: To date, most studies of the 'allergy epidemic' have been based on self-reported data. There is still limited knowledge on time trends in allergic sensitization, especially among adults. OBJECTIVE: To study allergic sensitization, its risk factors and time trends in prevalence. METHODS: Within West Sweden Asthma Study (WSAS), a population-based sample of 788 adults (17-60 years) underwent skin prick tests (SPTs) for 11 aeroallergens 2009-2012. Specific IgE was analysed in 750 of the participants. Those aged 20-46 years (n = 379) were compared with the European Community Respiratory Health Survey sample aged 20-46 year from the same area (n = 591) in 1991-1992. RESULTS: Among those aged 20-46 years, the prevalence of positive SPT to pollen increased, timothy from 17.1% to 29.0% (P < 0.001) and birch from 15.6% to 23.7% (P = 0.002) between 1991-1992 and 2009-2012. Measurements of specific IgE confirmed these increases. Prevalence of sensitization to all other tested allergens was unchanged. In the full WSAS sample aged 17-60 years, any positive SPT was seen in 41.9%, and the dominating sensitizers were pollen (34.3%), animals (22.8%) and mites (12.6%). Pollen sensitization was strongly associated with rhinitis, whereas indoor allergens were more associated with asthma. Growing up with livestock or furred pets decreased the risk of sensitization, adjusted odds ratio 0.53 (0.28-0.995) and 0.68 (0.47-0.98), respectively. CONCLUSION: Pollen sensitization has increased in Swedish adults since the early 1990s, while the prevalence of sensitization to other allergens has remained unchanged. This is one plausible explanation for the increase in rhinitis 1990-2008 in Swedish adults, during which time the prevalence of asthma, which is more associated with perennial allergens, was stable. Contact with animals in childhood seems to reduce the risk of sensitization well into adulthood. One major factor contributing to the rise in pollen allergy is a significant increase in levels of birch and grass pollen over the past three decades.

Decreased importance of environmental risk factors for childhood asthma from 1996 to 2006.

BACKGROUND: The large increase in asthma prevalence continues in several, but not all areas. Despite the individual risk factors that have been identified, the reasons for the observed trends in prevalence are largely unknown. OBJECTIVE: This study sought to characterize what trends in risk factors accompanied trends in asthma prevalence. METHODS: Two population-based cohorts of 7- to 8-year-old children from the same Swedish study areas examined by expanded International Study of Asthma and Allergy in Childhood questionnaires were compared 10 years apart. In 1996 and 2006, 3430 (97% participation) and 2585 (96% participation) questionnaires were completed, respectively. A subset was skin-prick-tested: in 1996 and 2006, 2148 (88% participation) and 1700 (90% participation) children, respectively. The adjusted population-attributable fraction (aPAF) was calculated using the prevalence and multivariate odds ratio of each risk factor. RESULTS: The prevalence of current asthma and wheeze was similar in 1996 and 2006. Allergic sensitization, however, increased from 21% to 30%. The prevalence of parental asthma increased from 17% to 24%, while respiratory infections and maternal smoking decreased (60% to 29% and 32% to 16%, respectively). The aPAFs of non-environmental risk factors for current asthma increased in 1996-2006: allergic sensitization from 35% to 41%, parental asthma from 27% to 45% and male sex from 20% to 25%. Conversely, the aPAFs of environmental risk factors decreased: respiratory infections from 36% to 32% and damp home and maternal smoking from 14% and 19%, respectively, to near zero in 2006. CONCLUSIONS AND CLINICAL RELEVANCE: From 1996 to 2006, the non-environmental risk factors parental asthma, allergic sensitization and male sex had an increasing or constant importance for current asthma in 7- to 8-year-old children. The importance of the environmental exposures damp home, respiratory infections and maternal smoking decreased. This counterbalancing in risk factors may explain the level of prevalence of current asthma.

Aspirin-intolerant asthma in the population: prevalence and important determinants.

BACKGROUND: Population-based studies on aspirin-intolerant asthma (AIA) are very few, and no previous population study has investigated risk factors for the condition. OBJECTIVE: To investigate the prevalence and risk factors of AIA in the general population. METHODS: A questionnaire on respiratory health was mailed to 30,000 randomly selected subjects aged 16-75 years in West Sweden, 29,218 could be traced and 18,087 (62%) responded. The questionnaire included questions on asthma, respiratory symptoms, aspirin-induced dyspnoea and possible determinants. RESULTS: The prevalence of AIA was 0.5%, 0.3% in men and 0.6% in women (P = 0.014). Sick leave, emergency visits due to asthma and all investigated lower respiratory symptoms were more common in AIA than in aspirin-tolerant asthma (ATA). Obesity was a strong risk factor for AIA (BMI > 35: odds ratio (OR) 12.1; 95% CI 2.49-58.5), and there was a dose-response relationship between increasing body mass index (BMI) and risk of AIA. Obesity, airborne occupational exposure and visible mould at home were considerably stronger risk factors for AIA than for ATA. Current smoking was a risk factor for AIA (OR 2.55; 95% CI 1.47-4.42), but not ATA. CONCLUSION: Aspirin-intolerant asthma identified in the general population was associated with a high burden of symptoms, uncontrolled disease and a high morbidity. Increasing BMI increased the risk of AIA in a dose-response manner. A number of risk factors, including obesity and current smoking, were considerably stronger for AIA than for ATA.

Gas, dust, and fumes exposure is associated with mite sensitization and with asthma in mite-sensitized adults.

Occupational exposure to gas, dust, and fumes (GDF) increases the risk of asthma and eczema. We investigated the role of sensitization in the association between GDF and allergic conditions. A population-based sample of 788 adults from the West Sweden Asthma Study completed questionnaires and skin prick tests. After adjustment for confounders, GDF exposure was associated with a doubled risk of sensitization to mites, but not with other allergens. Mite sensitization also modified the effect of GDF on asthma. In mite-sensitized subjects, GDF was associated with physician-diagnosed asthma, adjusted OR 2.9 (1.2-7.2), and with wheeze, OR 2.4 (1.1-5.3). In non-mite-sensitized subjects, the corresponding ORs were 1.1 (0.5-2.6) and 0.6 (0.3-1.3). GDF was independently associated with eczema regardless of mite sensitization, but not with rhinitis. These novel findings suggest that components of GDF may act as adjuvants that facilitate sensitization to mites and that mite-sensitized individuals may be especially susceptible to inhalant occupational exposures.

Eczema among adults: prevalence, risk factors and relation to airway diseases. Results from a large-scale population survey in Sweden.

BACKGROUND: In contrast to asthma and rhinitis, few studies among adults investigating the prevalence and risk factors of eczema have been published. OBJECTIVES: To investigate the prevalence and risk factors of eczema among adults in West Sweden. A further aim was to study the associations between asthma, rhinitis and eczema. METHODS: A questionnaire on respiratory health was mailed in 2008 to 30,000 randomly selected subjects in West Sweden aged 16-75 years; 62% responded. The questionnaire included questions about eczema, respiratory symptoms and diseases and their possible determinants. A subgroup of 669 subjects underwent skin prick testing against common airborne allergens. RESULTS: 'Eczema ever' was reported by 40·7% and 'current eczema' by 11·5%. Both conditions were significantly more common among women. The prevalence decreased with increasing age. The coexistence of both asthma and rhinitis with eczema was common. The main risk factors were family history of allergy and asthma. The dominant environmental risk factor was occupational exposure to gas, dust or fumes. Smoking increased the risk. Eczema was associated with urbanization, while growing up on a farm was associated with a decreased risk. Added one by one to the multivariate model, asthma, allergic rhinitis and any positive skin prick test were associated with eczema. CONCLUSIONS: Eczema among adults is a common disease with more women than men having and having had eczema. Eczema is associated with other atopic diseases and with airway symptoms. Hereditary factors and exposure to gas, dust and fumes are associated with eczema.

Multi-symptom asthma as an indication of disease severity in epidemiology.

Epidemiological questionnaires have failed to identify individuals with severe asthma. The extent of symptoms of asthma can, however, be easily established in epidemiology, by identification of multiple symptoms. We hypothesise that reporting of multiple symptoms of asthma reflects uncontrolled disease and is a sign of more severe asthma. The aims of the current study were, therefore, to determine the prevalence and determinants of multi-symptom asthma. A postal questionnaire was sent to 30,000 randomly selected individuals aged 16-75 yrs. A subgroup underwent clinical examinations. Multi-symptom asthma was defined as reported physician-diagnosed asthma, use of asthma medication, recurrent wheeze, attacks of shortness of breath and at least one additional respiratory symptom. The prevalence of multi-symptom asthma was 2.0%, and it was more common among females (2.4 versus 1.5%; p<0.001) and those with a body mass index >30 kg · m(-2). Multi-symptom asthmatics had lower forced expiratory volume in 1 s, higher exhaled nitric oxide fraction and more pronounced hyperresponsiveness. Family history of both asthma and allergy (OR 7.3), and occupational exposure to gas dust or fumes (OR 2.0) were also significant risk factors. Multi-symptom asthmatics comprise 2% of the general population; multi-symptom asthma is related to signs of more severe disease and could be used as an epidemiological marker of disease severity.

Assessment of problematic severe asthma in children.

Assessment of problematic severe asthma in children should be performed in a step-wise manner to ensure an optimal approach. A four-step assessment scheme is proposed. First, a full diagnostic work-up is performed to exclude other diseases which mimic asthma. Secondly, a multi-disciplinary assessment is performed to identify issues that may need attention, including comorbidities. Thirdly, the pattern of inflammation is assessed, and finally steroid responsiveness is documented. Based upon these four steps an optimal individualised treatment plan is developed. In this article the many gaps in our current knowledge in all these steps are highlighted, and recommendations for current clinical practice and future research are made. The lack of good data and the heterogeneity of problematic severe asthma still limit our ability to optimise the management on an individual basis in this small, but challenging group of patients.

Bed-sharing among six-month-old infants in western Sweden.

AIM: In spite of several reports of an increased risk of sudden infant death syndrome (SIDS) in connection with bed-sharing, it is not an uncommon practice. The aim of this study was to examine bed-sharing at 6 months of age and the factors that are associated with bed-sharing. METHODS: Our cohort comprised 8176 randomly chosen families. At 6 month of age, the families received an invitation to the study, with a questionnaire, which was completed by 5605 families (response rate 68.5%). RESULTS: Of the families, 19.8% bed-shared. In the multivariate analysis, we found a correlation between breast-feeding and bed-sharing (breast-feeding at 6 months: OR 1.94; 95% CI 1.56, 2.41). Moreover, we found an association with 3+ nightly awakenings at 6 months (2.70; 2.20, 3.32). It was more common to share a bed if the parent was single (2.04; 1.19, 3.51) and less common if the infant was bottle-fed in the first week (0.70; 0.54, 0.90). Never using a pacifier was associated with a higher frequency of bed-sharing. CONCLUSION: We found a correlation between breast-feeding and bed-sharing as well as between sleeping problems and a single parent. A lower percentage of infants sleeping in the parental bed were seen in association with formula feeding in the first week after birth.

Problematic severe asthma in children, not one problem but many: a GA2LEN initiative.

Although most children with asthma are easy to treat with low doses of safe medications, many remain symptomatic despite every therapeutic effort. The nomenclature regarding this group is confusing, and studies are difficult to compare due to the proliferation of terms describing poorly defined clinical entities. In this review of severe asthma in children, the term problematic severe asthma is used to describe children with any combination of chronic symptoms, acute severe exacerbations and persistent airflow limitation despite the prescription of multiple therapies. The approach to problematic severe asthma may vary with the age of the child, but, in general, three steps need to be taken in order to separate difficult-to-treat from severe therapy-resistant asthma. First, confirmation that the problem is really due to asthma requires a complete diagnostic re-evaluation. Secondly, the paediatrician needs to systematically exclude comorbidity, as well as personal or family psychosocial disorders. The third step is to re-evaluate medication adherence, inhaler technique and the child's environment. There is a clear need for a common international approach, since there is currently no uniform agreement regarding how best to approach children with problematic severe asthma. An essential first step is proper attention to basic care.

Growing up on a farm leads to lifelong protection against allergic rhinitis.

BACKGROUND: Various studies have reported a low prevalence of allergic rhinitis in farmers and farmers' children. We sought to investigate whether the protective effect of childhood farm environment is conserved throughout adulthood and how it corresponds to different degrees of urbanization. METHODS: A questionnaire on respiratory health was mailed in 2008 to 30,000 randomly selected subjects aged 16-75 in West Sweden, 29,218 could be traced and 18,087 (62%) responded. The questionnaire included questions on allergic rhinitis, asthma, respiratory symptoms and possible determinants. RESULTS: When stratified into age groups of 15 years, subjects that lived on a farm during their first 5 years of life had a lower prevalence of allergic rhinitis in all groups, even among the oldest (61-75 years). The negative correlation between childhood farm living and prevalence of allergic rhinitis was similar in 46-75 years of age (OR 0.82; 95% CI 0.70-0.95) as in 16-45 years of age (OR 0.78; 0.64-0.95). There was a significant trend of increasing prevalence of allergic rhinitis with increasing degree of urbanization independent of the effect of childhood farm living. CONCLUSIONS: We found a lifelong protective effect of childhood farm living on the prevalence of allergic rhinitis. In addition, we found an increasing prevalence of allergic rhinitis with increasing degree of urbanization both in those raised on a farm and those not, thus emphasizing the influence of both childhood and adult exposure for the development of allergic disease.

Increased prevalence of otitis media following respiratory syncytial virus infection.

AIM: The aim of this study was to analyse whether, during the 18 months following a respiratory syncytial virus (RSV) infection in infants, there were differences in the prevalence of common infections such as acute otitis media (AOM), compared with controls. We also wanted to see whether passive smoking could be a contributory factor. METHODS: In a longitudinal study, 33 children who attended the emergency room with an RSV infection (age < or = 7 months) were compared with 37 age-matched controls recruited from routine infant check-ups. The 18-month follow-up consisted of a questionnaire focusing on environmental factors and the child's health during the last 12 months. An allergy skin prick test (SPT) was performed and venous blood was obtained. RESULTS: The prevalence of AOM and the use of antibiotics were higher in the RSV group than in the controls (p = 0.009 and p = 0.027 respectively). The number of AOMs and the use of antibiotics correlated, r = 0.8. In the RSV group, one or both parents smoked in 52% compared with 14% in the controls (p < 0.001). There were no differences in allergy SPT results. CONCLUSION: The infants with RSV infection had AOM and were prescribed antibiotics more frequently during the follow-up period. Furthermore, smoking was far more common among the parents of the RSV group. We speculate that passive smoking could be a contributory factor to the infections noted here.

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach.

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Determinants of lung function and airway hyperresponsiveness in asthmatic children.

BACKGROUND: Asthma patients exhibit an increased rate of loss of lung function. Determinants to such decline are largely unknown and the modifying effect of steroid therapy is disputed. This cross-sectional study aimed to elucidate factors contributing to such decline and the possible modifying effect of steroid treatment. METHODS: We analyzed determinants of lung function and airway hyperresponsiveness (AHR) in a Scandinavian study of 2390 subjects from 550 families. Families were selected for the presence of two or more asthmatic children as part of a genetic study, Scandinavian Asthma Genetic Study (SAGA). RESULTS: The primary analysis studied the association between the lung function and delay of inhaled corticosteroids (ICS) after asthma diagnosis among asthmatic children and young adults with a history of regular ICS treatment (N=919). FEV(1) percent predicted (FEV(1)% pred) was 0.25% lower per year of delay from diagnosis until treatment (p=0.039). This association was significantly greater in allergy skin prick test negative children. There was no significant influence of gender, age at asthma onset, or smoking. In the secondary analysis of the whole population of 2390 asthmatics and non-asthmatics, FEV(1)% pred was inversely related to having asthmatic siblings (-7.9%; p<0.0001), asthma diagnosis (-2.7%; p=0.0007), smoking (-3.5%; p=0.0027), and positive allergy skin prick test (-0.47% per test; p=0.012), while positively related to being of female gender (1.8%; p=0.0029). Risk of AHR was higher by having asthmatic siblings (OR 2.7; p<0.0001), being of female gender (OR 2.0; p<0.0001), and having asthma (OR 2.0; p<0.0001). CONCLUSIONS: These data suggest that lung function is lower in asthmatics with delayed introduction of ICS therapy, smoking, and positive allergy skin prick test. Lung function is lower and AHR higher in female asthmatics and subjects with asthmatic siblings or established asthma.

Obstetric characteristics and neonatal performance in a four-year small for gestational age population.

Obstetric and neonatal performance were analyzed in an ultrasound-dated small for gestational age (SGA) population from 1982-1985. Eighty-three percent of 160 SGA infants were identified antenatally by means of intrauterine growth retardation (IUGR) risk scoring, and the pregnancies were supervised at a high-risk clinic. Fifty percent were delivered electively, predominantly in gestational weeks 38-39. Thirty percent were born preterm. The cesarean section rate was 40%. Perinatal mortality was 6%, or 4% when lethal malformations were excluded, ten times higher than the corresponding total population figures. Eleven percent of the fetuses had severe malformations. In the remaining SGA population, one infant died after experiencing severe perinatal asphyxia and another developed cerebral palsy; no other major sequelae were found before the age of 18 months. Hypoglycemia and hypothermia occurred frequently, but these problems were managed satisfactorily. The mean hospital stay for term infants was twice that of appropriate for gestational age infants. We conclude that the extra attention paid to the SGA population is well motivated. Future efforts should be directed toward improving the diagnostic techniques for IUGR, as most of the perinatal mortality occurred among SGA infants not identified before birth.

The role of cardiac receptors in clonidine-induced vagal bradycardia.

In chloralosed, spinalized and beta-blocked cats, clonidine, 10 microgram/kg i.v. caused a vagally mediated bradycardia which was further analysed with particular attention to cardiopulmonary receptors. Cardiovascular deafferentiation, with preservation of vagal cardiac efferents, abolished the bradycardia. However, in animals with arterial baroreceptors denervated but with vagal cardiopulmonary pathways intact, clonidine decreased heart rate simultaneously with an increase in left atrial pressure to an extent known to activate cardiac receptors with unmyelinated vagal efferents. Clonidine somewhat enhanced the bradycardia to efferent vagal stimulation and also had a slight positive chronotropic effect on the non-innervated heart. The reflex bradycardia from electrical stimulation of unmyelinated cardiac afferents was augmented by the drug but not more than could be accounted for by the changed neuroeffector sensitivity. The data suggest that clonidine can reflexly augment vagal tone on the heart by an increased activity in vagal cardiac afferents, secondary to the drug's peripheral vasoconstrictor action, whereas no evidence for any central facilitation of these reflexes has been found.

Inhibitory effects of theophylline, terbutaline, and hydrocortisone on leukotriene B4 and C4 generation by human leukocytes in vitro.

Leukotriene B4 (LTB4) and leukotriene C4 (LTC4) are considered to be important mediators in the pathophysiology of asthma. Theophylline, terbutaline, and hydrocortisone are drugs commonly used in the treatment of asthma. In the present study we have investigated the in vitro inhibitory effects of theophylline, terbutaline, and hydrocortisone on LTB4 and LTC4 generation from human leukocytes. After preincubation in the presence of these drugs, the cells were stimulated with the calcium ionophore A 23187 and the supernatants were analyzed for their LTB4 and LTC4 content using reverse-phase high-performance liquid chromatography (HPLC). Total leukotriene (LT) production (the combined amounts of LTB4 and LTC4) was dose-dependently inhibited by pretreatment with theophylline, terbutaline or hydrocortisone. Therapeutic levels of hydrocortisone (5 x 10(-6) M) plus theophylline (5 x 10(-5) M) inhibited LTB4 and LTC4 production in an additive way, as did the combination of hydrocortisone plus terbutaline (5 x 10(-8) M). A statistically significant effect of diminished LTB4 generation was obtained after preincubation with therapeutic levels of theophylline plus terbutaline, but no such effect was seen for LTC4 levels. The in vitro inhibitory effects on LTB4 and LTC4 generation from human leukocytes by theophylline, terbutaline, and hydrocortisone, as well as the additive effect of hydrocortisone plus theophylline or terbutaline, add to our understanding of the therapeutic effects of these drugs in the treatment of bronchopulmonary obstruction.

Transcutaneous blood gas monitoring during salbutamol inhalations in young children with acute asthmatic symptoms.

The effect of salbutamol inhalations on transcutaneous blood gases was investigated in 23 children (aged 11 months-2.5 years) with asthmatic symptoms. After one salbutamol inhalation there was a mean increase in transcutaneous PO2 (tcPO2) of 0.5 kPa (P less than 0.01); after a second dose given 30 minutes later, the mean increase was 1.2 kPa (P less than 0.001). The increase in tcPO2 after only one dose of salbutamol was significantly correlated to age (P less than 0.01). No such correlation was observed after a second dose. The overall increase in tcPO2 after two salbutamol inhalations showed a negative correlation to the duration of the current symptomatic period (P less than 0.05). We conclude that salbutamol inhalations have beneficial effects in young children with acute asthmatic symptoms, even below the age of 18 months, provided that an adequate dose reaches the lung and preferably at an early stage of obstruction.

Low levels of exhaled nitric oxide are associated with impaired lung function in cystic fibrosis.

Fraction of exhaled nitric oxide (FENO) is often reduced in cystic fibrosis (CF). FENO at different expiratory flows can provide an indication of the site of nitric oxide production. The aim of this study was to examine whether NO parameters are related to overall (FEV(1)) or peripheral (lung clearance index, LCI, measured by multiple breath SF(6) washout) airway function and systemic inflammation in CF. Secondary aim was to compare alveolar NO and bronchial NO flux calculated by two different mathematical models, a linear and a nonlinear method. Thirty-five healthy and 45 CF children were recruited. FENO at 50 ml/sec (FENO(50)) and bronchial NO flux were lower in CF than controls, 9.5 (2.7-38.8) (median (range)) versus 12.4 (5.2-40.1) ppb, P = 0.029, and 391 (97-1772) versus 578 (123-1993) (pl/sec), P = 0.036, respectively. No difference in alveolar NO was shown. The nonlinear method resulted in lower alveolar NO and higher bronchial flux, than the linear method, but the result was closely correlated in both groups. LCI was higher in CF than controls, 8.4 (6.5-12.9) versus 5.9 (5.1-7.8), P < 0.001. FENO(50) was negatively correlated with LCI (r = -0.43; P = 0.003) and positively correlated with FEV(1) (r = 0.42, P = 0.004) in CF. Alveolar NO correlated negatively with inflammatory markers: orosomucoid (r = -0.42, P = 0.005), platelets (r = -0.50, P < 0.001) and white blood cell count (r = -0.48, P = 0.001). In conclusion, FENO(50) and bronchial NO flux are reduced in young CF subjects and low FENO(50) is associated with overall and small airway obstruction. NO parameters derived from the different models were closely related but the values differed slightly.