Adults with concomitant atopic dermatitis and asthma have more frequent urgent healthcare utilization and less frequent scheduled follow-up visits than adults with atopic dermatitis or asthma only: a nationwide cohort study.

BACKGROUND: Atopic dermatitis (AD) and asthma often co-occur in the same patient, and healthcare utilization is related to disease severity of these diseases. OBJECTIVE: The objective of the study was to investigate differences in healthcare utilization in adults with concomitant AD and asthma compared to patients with asthma or AD only. METHODS: All Danish adults with a hospital diagnosis of AD, asthma or concomitant AD, and asthma recorded in national registries were included. Healthcare utilization data were obtained in 3-month intervals from 2 years prior to index date (the date of the first hospital diagnosis) and to 5 years after. RESULTS: A total of 12 409 patients with AD were included (11 590 with AD only and 819 with concomitant AD and asthma), and 65 539 with asthma only. Adults with concomitant AD and asthma had higher risk of hospitalization for AD (OR 1.38, 95% CI (1.15-1.67), P = 0.001) and asthma (OR 1.16, 95% CI (1.00-1.35), P = 0.047) compared to patients with only AD and asthma, respectively. These patients also had fewer visits in outpatient clinics for AD (OR 0.10, 95% CI (0.08-0.12), P < 0.001) and asthma (OR 0.34, 95% CI (0.29-0.39), P < 0.001) compared to patients with only AD or asthma. Outpatient clinic visits for rhinitis were more frequent among patients with concomitant AD and asthma compared to patients with only AD or asthma. CONCLUSION: Adults with concomitant AD and asthma had different patterns of healthcare utilization compared to adults with AD or asthma alone, suggesting that improvements in management and monitoring may reduce unscheduled healthcare visits and lower healthcare costs.

Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. METHODS: The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. DISCUSSION: The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.

Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers : A Randomized Controlled Trial.

BACKGROUND: Observational evidence suggests that mask wearing mitigates transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is uncertain if this observed association arises through protection of uninfected wearers (protective effect), via reduced transmission from infected mask wearers (source control), or both. OBJECTIVE: To assess whether recommending surgical mask use outside the home reduces wearers' risk for SARS-CoV-2 infection in a setting where masks were uncommon and not among recommended public health measures. DESIGN: Randomized controlled trial (DANMASK-19 [Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection]). (ClinicalTrials.gov: NCT04337541). SETTING: Denmark, April and May 2020. PARTICIPANTS: Adults spending more than 3 hours per day outside the home without occupational mask use. INTERVENTION: Encouragement to follow social distancing measures for coronavirus disease 2019, plus either no mask recommendation or a recommendation to wear a mask when outside the home among other persons together with a supply of 50 surgical masks and instructions for proper use. MEASUREMENTS: The primary outcome was SARS-CoV-2 infection in the mask wearer at 1 month by antibody testing, polymerase chain reaction (PCR), or hospital diagnosis. The secondary outcome was PCR positivity for other respiratory viruses. RESULTS: A total of 3030 participants were randomly assigned to the recommendation to wear masks, and 2994 were assigned to control; 4862 completed the study. Infection with SARS-CoV-2 occurred in 42 participants recommended masks (1.8%) and 53 control participants (2.1%). The between-group difference was -0.3 percentage point (95% CI, -1.2 to 0.4 percentage point; P = 0.38) (odds ratio, 0.82 [CI, 0.54 to 1.23]; P = 0.33). Multiple imputation accounting for loss to follow-up yielded similar results. Although the difference observed was not statistically significant, the 95% CIs are compatible with a 46% reduction to a 23% increase in infection. LIMITATION: Inconclusive results, missing data, variable adherence, patient-reported findings on home tests, no blinding, and no assessment of whether masks could decrease disease transmission from mask wearers to others. CONCLUSION: The recommendation to wear surgical masks to supplement other public health measures did not reduce the SARS-CoV-2 infection rate among wearers by more than 50% in a community with modest infection rates, some degree of social distancing, and uncommon general mask use. The data were compatible with lesser degrees of self-protection. PRIMARY FUNDING SOURCE: The Salling Foundations.

Small intestinal absorption in patients with chronic obstructive pulmonary disease complicated by cor pulmonale - A pilot study.

BACKGROUND: Cor pulmonale is a common complication to Chronic Obstructive Pulmonary Disease (COPD), and may result in increased pressure in the inferior caval vein and stasis of the liver. The chronic pulmonary hypertension may lead to stasis in the veins from the small intestine and thereby compromise absorption of nutrients. AIM: To investigate whether patients with pulmonary hypertension have reduced absorption capacity compared to COPD patients without cor pulmonale. METHODS: Absorption of d-xylose (25 g) and zinc (132 mg), administered as a single dose, was tested in 14 COPD patients, seven with and seven without cor pulmonale. The presence of cor pulmonale was determined by echocardiography. The concentration of d-xylose and zinc were measured in peripheral blood one, two and three hours after ingestion and used as markers of absorption. Furthermore, urine was collected for five hours to determine the amount of excreted d-xylose. RESULTS: No significant difference in absorption of d-xylose (p = 0.28) or zinc (p = 0.51) was found between the two groups. However, a trend towards a delay in d-xylose absorption, as assessed by time-to-peak concentration, was observed in patients with cor pulmonale (p = 0.08). There was no significant difference in the amount of excreted d-xylose in the urine between the groups (p = 0.52). No correlation was found between the tricuspid regurgitation gradient and the absorption of both test-markers (rs = 0.34 and rs = -0.25). Likewise, no correlations were found between the inferior caval pressure during the in- and expiration phases and the absorption of d-xylose (rs = -0.09 rs = 0.23) or zinc (rs = -0.39, rs = -0.39). CONCLUSION: We found no indications that small intestinal absorption is affected in a clinically relevant degree in patients with cor pulmonale.

Is atopic dermatitis associated with obesity? A systematic review of observational studies.

Obesity has been associated with atopic dermatitis (AD); however, the results have been conflicting. Our aim was to provide an update on current knowledge from observational studies addressing the possible association between obesity and AD. Systematic literature review was performed by identifying studies addressing a possible link between AD and overweight/obesity from PubMed, EMBASE and the Cochrane Library in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. A total of 45 studies (comprising more than 90 000 individuals with AD) fulfilled the criteria and were included in the present review. The available studies revealed inconsistencies, but the majority indicated that obesity is associated with AD. Studies addressing obesity in infancy or early childhood (age < 2 years) and AD reported a positive association. From childhood into adulthood, there is a discrepancy in the observations, as the more recent prospective studies found a positive association, whereas this was not observed in older cross-sectional studies. The inconsistency might be explained by the difference in study design, the diagnostic criteria of AD, regional differences, and by the varied definitions of overweight and obesity used in the studies. In Conclusion, overweight/obesity is associated with an increased risk of AD. Large prospective cohort studies are required to confirm the association between AD and obesity and the possibility that weight control in childhood may help to mitigate or reverse AD symptoms.

Overweight in childhood and adolescence: Does it lead to airway hyperresponsiveness in adulthood?

BACKGROUND: Obesity is increasing worldwide among children and adolescents, and has been associated with an increased incidence of asthma. However, the mechanisms underlying this association are incompletely understood. OBJECTIVE: In this cohort study we aimed to investigate whether being overweight in childhood and adolescence is associated with an increased risk of airway hyperresponsiveness (AHR), a hallmark of asthma, in early adulthood. METHODS: Of 527 subjects from a random population sample of children and adolescents (7-17 years) examined at baseline, a total of 184 subjects completed the follow-up visit 20 years later and were included in the present analysis. Both visits included assessment of height and weight, case history and spirometry. At both visits, bronchial provocation tests were performed using either histamine (baseline) or methacholine (follow-up). In addition, fractional exhaled nitric oxide (FeNO) was measured at follow-up. RESULTS: No significant difference in the prevalence of AHR at follow-up was found between subjects who were overweight or obese at baseline visit (n = 26) (pediatric definition, body mass index ≥ 85%percentile) and normal weight subjects (n = 158) (positive bronchial provocation tests: 15.4% vs. 22.2%, respectively, p = 0.35). Likewise, follow-up FeNO levels did not differ significantly between subjects who were lean and those who were overweight or obese at baseline (geometric mean (95% confidence interval [CI]) 15.1 (13.7, 16.6) parts per billion (ppb) versus 13.0 (10.6, 15.9) ppb, p = 0.23). CONCLUSION: In children and adolescents, being obese or overweight seems not to be associated with an increased risk of AHR or increased FeNO levels in early adulthood.

Determinants of low risk of asthma exacerbation during pregnancy.

BACKGROUND: Assessment of asthma control every 4-6 weeks during pregnancy is recommended to reduce risk of exacerbation, and by that improve outcome. OBJECTIVE: To identify determinants of pregnancies with low risk of asthma exacerbation. METHODS: All pregnant women enrolled into the Management of Asthma during Pregnancy (MAP) programme at Hvidovre Hospital since 2007. Assessment of asthma control, adjustment of treatment, spirometry and measurement of exhaled nitric oxide (FE NO) were performed, and baseline characteristics and exacerbation history were collected at enrolment. Determinants of low-exacerbation risk pregnancies were identified by logistic regression analysis (stepwise backward elimination). RESULTS: In 1283 pregnancies, 107 exacerbations were observed. Multiple regression analysis revealed that no history of pre-pregnancy exacerbations (P < .001), no prescribed controller medication (P < .001), and clinically stable asthma at enrolment (P = .002) were significantly associated with low risk of exacerbation during pregnancy; with these combined characteristics, only two of 385 pregnancies were complicated by an exacerbation (OR 0.04, 95% CI 0.01-0.18, P < .001). CONCLUSION AND CLINICAL RELEVANCE: Clinically stable asthma at enrolment, together with no history of previous exacerbations and no prescribed controller medication, is a determinant of low risk of an asthma exacerbation during pregnancy, which may guide clinicians in individualizing surveillance of asthma during pregnancy.

Exacerbations of asthma during pregnancy: Impact on pregnancy complications and outcome.

Asthma is common among pregnant women, and the incidence of asthma exacerbations during pregnancy is high. This literature review provides an overview of the impact of exacerbations of asthma during pregnancy on pregnancy-related complications. The majority of published retrospective studies reveal that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive care unit and longer postpartum hospital stay. Asthma has been associated with increased risk of intrauterine growth retardation, small-for-gestational age, low birth weight, infant hypoglycaemia and preterm birth, but more recent prospective studies have not revealed significant associations with regard to these outcomes. In conclusion, asthma exacerbations during pregnancy are associated with complications of pregnancy, labour and delivery. Prevention of exacerbations is essential to reduce the risk of complications and poor outcome.

Deferral of surgery for epiretinal membranes: Is it safe? Results of a randomised controlled trial.

BACKGROUND/AIMS: To compare the visual outcome in early versus deferred surgery in patients with idiopathic epiretinal membrane (ERM) and good presenting visual acuity and mild symptoms. METHODS: This study is a randomised clinical trial. 53 eyes of 53 patients with symptomatic ERM and best-corrected visual acuity (BCVA) at presentation ≥65 early treatment diabetic retinopathy study (ETDRS) letters were randomised to immediate surgery (20 eyes) or to watchful waiting (33 eyes) for 1 year. Primary end-point was BCVA after 12 months. Secondary end-points were central macular thickness and the number of patients that crossed over from the watchful waiting arm to the surgery arm due to deteriorated symptoms. RESULTS: Mean BCVA after 12 months in the watchful waiting group (81 letters) were not significantly different from patients undergoing immediate surgery (82.5 letters, p=0.647). During 1 year of follow-up, eight patients in the watchful waiting group (24%) crossed over to surgery and these patients gained a mean of 3.1 letters (SEM 1.38). Patients randomised to immediate surgery gained approximately one line. Watchful waiting patients who remained without surgery were stable. The visual acuity gain after surgery is slow and gradual until 9 months postoperatively. There were no serious complications such as retinal detachment or infectious endophthalmitis. CONCLUSIONS: Vitrectomy for early symptomatic ERM is beneficial in preserving excellent vision. A watchful waiting approach with 1 year of follow-up is safe in the sense that this group does not lose five ETDRS letters in waiting. Deferral of surgery by regular monitoring of patients is a safe approach. TRIAL REGISTRATION NUMBERS: H-C-2008-026 and NCT00902629.

High tobacco consumption lowers body weight: a Mendelian randomization study of the Copenhagen General Population Study.

BACKGROUND: Conflicting evidence has been found regarding the association between high tobacco consumption and body weight among smokers. We tested the hypothesis that high tobacco consumption is causally associated with low body weight. METHODS: We conducted a Mendelian randomization study with a genetic variant in CHRNA3 (rs1051730) as proxy for high tobacco consumption. The cohort consisted of 80,342 participants from the Copenhagen General Population Study, with details on body weight, smoking habits and CHRNA3 genotype, including 15,220 current smokers. RESULTS: In observational analyses, high tobacco consumption was associated with high body weight, body mass index, waist circumference, hip circumference and waist-hip ratio. In multivariable adjusted models a 1-cigarette/day higher tobacco consumption was associated with 0.05 kg (95% confidence interval 0.02; 0.08) higher body weight, 0.02 kg/m(2) (0.01; 0.02) higher body mass index, 0.10 cm (0.07; 0.12) higher waist circumference and 0.02 cm (0.001; 0.03) higher hip circumference. In contrast, the per-allele increase inCHRNA3 rs1051730 associated with high tobacco consumption was associated with 0.59 kg (0.96; 0.22) lower body weight, 0.23 kg/m(2) (0.33; 0.13) lower body mass index, 0.32 cm (0.74; 0.003) lower waist circumference and 0.45 cm (0.66; 0.24) lower hip circumference. No association was found between tobacco consumption and waist-hip ratio in genetic analysis, or among CHRNA3 genotype and any of the outcome variables in former or never smokers. CONCLUSIONS: High tobacco consumption causes lower body weight among current smokers. However, smoking does not seem to affect body shape or fat distribution causally. The lack of association between CHRNA3 genotype and body weight among former smokers and never smokers favours smoking as the causal factor for the observed associations.

Visual loss after use of intraocular silicone oil associated with thinning of inner retinal layers.

PURPOSE: To investigate the incidence and cause of severe visual loss following use and removal of intraocular silicone oil (SiO) after uncomplicated vitrectomy and SiO injection for primary rhegmatogenous retinal detachment (RRD). METHODS: Consecutive case series of 216 patients operated with vitrectomy for primary RRD in 2004-2005. In 162 eyes, SiO (5500 centiStoke) had been used as intravitreal tamponade and in 54 eyes gas (perflouropropane, C(3) F(8) ) had been used. Following chart review, we identified 16 eyes in 16 patients (nine SiO eyes, seven gas eyes) with macula-on and documented visual acuity ≥6/12 before surgery, where SiO had been removed, cataract surgery performed and no re-detachment had occurred. Examinations included best-corrected visual acuity (BCVA) and high-definition optical coherence tomography (OCT) of the macular area. RESULTS: Preoperative characteristics were identical between SiO and gas eyes. Postoperative BCVA was significantly worse in SiO eyes (>6/24) compared to gas eyes (>6/7.5), p = 0.005. Three of 9 (33%) SiO eyes had final BCVA ≤6/60 and 67% had final BCVA ≤6/12. No gas eyes had final BCVA <6/9. Macular OCT revealed thinning of inner retinal layers in SiO-operated eyes (5148 pixels) compared to gas-operated eyes (6897 pixels), p < 0.002. No other visually significant structural differences were found. CONCLUSION: Severe visual loss after SiO use was observed in 1/3 of patients with otherwise good visual potential. The visual loss was associated with a significant reduction in inner retinal thickness indicating neuronal cell loss in the macular area as a possible explanation.

Add-on montelukast to inhaled corticosteroids protects against excessive airway narrowing.

RATIONALE: Excessive airway narrowing in response to broncho-active stimuli is a predictor for severe exacerbations in asthma. Leukotriene receptor antagonists (LTRAs) have complementary properties to inhaled corticosteroids (ICS) on asthma control. OBJECTIVES: The LTRA montelukast may provide an additional protection against excessive airway narrowing. We tested the add-on effects of montelukast on the maximal response plateau and PD(20) to inhaled methacholine in asthmatics on a stable dose of ICS. METHODS: Thirty-one patients with allergic asthma [14M/17F, 19-50 years, forced expiratory volume in 1 s (FEV(1)) >70% pred., PD(20) <3.9 micromol methacholine], with a twice documented response plateau to methacholine, were randomized in a double-blind (montelukast 10 mg or matching placebo once daily), 12-week parallel study. Bronchoprovocation tests with methacholine (0.03-256 micromol or > or =40% decline in FEV(1)) were repeated every 4 weeks and after wash-out. The main study objectives were changes from baseline in maximal FEV(1) decline at the response plateau (i.e. >2 post-dose FEV(1) values within 5%) and PD(20) to methacholine after 12 weeks' treatment. RESULTS: Neither treatment affected baseline FEV(1) (P=0.62). Compared with placebo, montelukast significantly decreased the maximal response plateau to methacholine (mean difference 9.4%; 95% confidence interval 3.9-15.7; P<0.005), improved the FEV(1) decline (mean change in FEV(1) decline was 2.1% [montelukast] and -0.8% [placebo], respectively, P<0.05), and increased PD(20) methacholine (mean change in PD(20) of 5.3 [montelukast] and 1.4 [placebo] doubling doses, respectively, P<0.001). CONCLUSION: Add-on montelukast to ICS has disease-modifying effects in adults with persistent asthma, and hence reduces the risk of excessive airway narrowing (NCT 00913328).

Prognostic significance of delayed structural recovery after macular hole surgery.

PURPOSE: To assess the prognostic significance for visual function of persistent subfoveal fluid and persistent photoreceptor layer discontinuity in eyes in which hole closure had been obtained 3 months after macular hole surgery. DESIGN: Ancillary study of subjects enrolled in a randomized clinical trial. PARTICIPANTS: Participants were recruited from a randomized clinical trial evaluating internal limiting membrane (ILM) peeling in macular hole surgery. The study included 74 eyes in which a contiguous retinal surface or a full attachment with a flat neuroretinal rim had been reestablished after macular hole surgery. METHODS: Contrast-enhanced optical coherence tomography was used to detect closure defects involving substrata of the retina with particular emphasis on the photoreceptor layer. Outcomes were compared with best-corrected visual acuity (BCVA) 12 months after surgery. MAIN OUTCOME MEASURES: Postoperative foveal configuration and foveal photoreceptor layer discontinuity diameter 3 months after macular hole surgery. RESULTS: Persistent subfoveal fluid 3 months after macular hole surgery, which was found in 36.5% of eyes, was not associated with a significantly different BCVA after 12 months compared with eyes with a fully attached fovea at 3 months (70.9 letters vs. 72.0 letters; P = 0.59). Receiver operating characteristics curve analysis identified persistent photoreceptor layer discontinuity of a diameter of more than 1477 microm after 3 months to be associated with poorer BCVA after 12 months (P<0.001), yet an overall reduction in discontinuity diameter from 3 to 12 months (P<0.001) was not correlated with a concurrent improvement in BCVA (r = -0.040; P = 0.81). Persistence of fluid and diameter of discontinuity at 3 months were not related to whether ILM peeling was used; however, secondary macular hole surgery had a significant influence on diameter of photoreceptor layer discontinuity at 3 months. CONCLUSIONS: Structural recovery in the form of photoreceptor layer discontinuity with a diameter of more than approximately 1500 microm 3 months after macular hole surgery was associated with poorer visual acuity after 12 months than less extensive discontinuity. Subfoveal fluid persisting after 3 months had disappeared after 12 months in all but 5 of 74 eyes and had no effect on final visual outcome.

Prevalence and severity of self-reported asthma in young adults, 1976-2004.

The aim of the present study was to describe the prevalence and severity of asthma in young Danish adults over three decades. Males and females aged 20-35 yrs were sampled from the population of Copenhagen for the three surveys (1976-1978, 1991-1993 and 2001-2004). A total of 3,285 (46% male) subjects answered a questionnaire, and had their height, weight, forced expiratory volume in 1 s (FEV1) and forced vital capacity measured. The prevalence of self-reported asthma was 1.5, 4.7 and 6.9%, respectively, in the three surveys (p<0.001). An increasing prevalence of asthma was observed in both males and females, although it was highest among females. The difference in FEV1 between asthmatic and nonasthmatic subjects gradually increased, being 2.3 (p = 0.56) and 14.2% of the predicted value (p<0.001), respectively, in 1976-1978 and 2001-2004. From the 1991-1994 survey, increasing body mass index, especially >30 kg.m(-2), was associated with a lower percentage predicted FEV1 (p< or =0.005), and further analyses suggested an additive effect of asthma and obesity on FEV1. The proportion of smokers declined from 60 to 38% (p<0.001). The prevalence and severity of asthma have continued to increase over the last three decades among young Danish adults, and the observed increase in severity seems, at least partly, to be related to the increase in prevalence of obesity.

Association between obesity and asthma in a twin cohort.

BACKGROUND: Obesity is linked to asthma in a yet poorly understood manner. We examined the relationship between obesity and asthma in a population-based sample of twins. METHODS: From the cohorts born between 1953 and 1982, who were enrolled in The Danish Twin Registry, a total of 29 183 twin individuals participated in a nationwide questionnaire study, where data on height, weight and asthma were collected. Latent factor models of genetic and environmental effects were fitted using maximum likelihood methods. RESULTS: The age-adjusted risk of asthma was increased both in obese females, OR = 1.96 (1.45-2.64), P < or = 0.001 and in obese males, OR = 1.59 (1.08-2.33), P = 0.02. According to best-fitting models, the heritability for obesity was 81% in males and 92% in females, whereas the heritability for asthma was 78% and 68% in males and females respectively. The age-adjusted genetic liabilities to obesity and asthma were significantly correlated only in females, r = 0.28 (0.16-0.38). CONCLUSIONS: Obese subjects have an increased risk for asthma, which in females seems partly because of common genes.

Multivariate genetic analysis of atopy phenotypes in a selected sample of twins.

BACKGROUND: Atopic traits often co-occur and this can potentially be caused by common aetiological relationships between traits, i.e. a common genetic or a common environmental background. OBJECTIVE: To estimate to what extent the same genetic and environmental factors influence wheeze, rhinitis, airway hyper-responsiveness (AHR), and positive skin prick test (posSPT) in a sample of adult twins. METHODS: Within a sampling frame of 21,162 twin subjects, 20-49 years of age, from the Danish Twin Registry, a total of 575 subjects (256 intact pairs and 63 single twins), who either themselves and/or their co-twins reported a history of asthma at a nationwide questionnaire survey, were clinically examined. Symptoms of wheeze and rhinitis were obtained by interview; airway responsiveness and skin test reactivity were measured using standard techniques. Correlations in liability between the different traits were estimated and latent factor models of genetic and environmental effects were fitted to the observed data using maximum likelihood methods. RESULTS: The various phenotypic correlations between wheeze, rhinitis, AHR and posSPT were all significant and ranged between 0.50 and 0.86. Traits that showed highest genetic correlations were wheeze-rhinitis (rho(A)=0.95), wheeze-AHR (rho(A)=0.85) and rhinitis-posSPT (rho(A)=0.92), whereas lower genetic correlations were observed for rhinitis-AHR (rho(A)=0.43) and AHR-posSPT (rho(A)=0.59). Traits with a high degree of environmental sharing were rhinitis-posSPT (rho(E)=0.92) and wheeze-posSPT (rho(E)=0.71), whereas a lower environmental correlation was seen for wheeze-rhinitis (rho(E)=0.25). The estimates were corrected for ascertainment and adjusted for age, sex, inhaled corticosteroids and smoking. CONCLUSIONS: Different atopic conditions share, to a large extent, a common genetic background. In particular, upper and lower respiratory symptoms seem to be different phenotypic expressions of a common set of genes. These results add new insight into the origins of clinical heterogeneity within atopy and should stimulate the search for pleiotropic genes of importance for these conditions.

Findings on the atopic triad from a Danish twin registry.

OBJECTIVE: To estimate to what extent the same genetic and environmental risk factors influence asthma, hay fever and eczema. DESIGN: From the nationwide Danish Twin Registry, twin cohorts born between 1953 and 1982 were contacted for a questionnaire survey, and a total of 29 183 twin individuals (86%) responded. Subjects were classified as cases when responding affirmatively to three questions about the lifetime occurrence of asthma, hay fever and eczema. Variance components twin analysis was conducted using maximum likelihood methods. RESULTS: The phenotypic (within-subject) correlations in liability between the different diseases were 0.57 (95% CI 0.54-0.59) for asthma and hay fever, 0.40 (95% CI 0.36-0.42) for asthma and eczema, and 0.33 (95% CI 0.29-0.36) for hay fever and eczema. Decomposition of these correlations into their genetic and environmental contributions showed that shared genes explained between 70% and 85% of the correlation between the different diseases. The remaining parts were explained by environmental factors shared between the diseases. CONCLUSION: To a large extent, atopic diseases share a common genetic background, although disease-specific genes also play a considerable role. These results can prove informative when counselling families with atopy, and may furthermore be used to guide the search for pleiotropic genes of importance for these diseases.

Risk factors for asthma in young adults: a co-twin control study.

BACKGROUND: The liability to asthma is influenced both by genetic and environmental factors. The objective of this study was to identify risk factors for asthma in young adult twin pairs during an 8-year period. METHODS: From the birth cohorts 1953-1982 of the Danish Twin Registry, 6,090 twin pairs who were initially unaffected with respect to asthma at a nationwide questionnaire-based study in 1994 participated in a similar follow-up study in 2002. Subjects were regarded incident asthma cases when responding affirmatively to the question 'Do you have, or have you ever had asthma'? in 2002. Pairs in which only one twin developed asthma -- discordant pairs -- were identified and conditional logistic regression was applied to detect effects of risk factors. RESULTS: A total of 126 monozygotic (MZ) and 273 dizygotic (DZ) discordant twin pairs were identified. In MZ twins hay fever (OR = 3.16, 95% CI: 1.29-7.73, P = 0.007) and exercise (OR for inactivity = 0.35, 95% CI: 0.13-0.91, P = 0.023) were significantly associated with asthma, whereas in DZ twins, hay fever (OR = 2.44, 95% CI: 1.44-4.13, P = 0.001), eczema (OR = 1.96, 95% CI: 1.02-3.78, P = 0.040), female sex (OR between males and females = 0.54, 95% CI: 0.36-0.80, P = 0.002), and increasing levels of body mass index (BMI; OR per unit = 1.11, 95% CI: 1.02-1.20, P = 0.009) were significant predictors of asthma. CONCLUSIONS: Hay fever, eczema, female sex, exercise and increasing levels of BMI were risk factors for asthma in young adults. The different risk profile observed in MZ twins compared with DZ twins may reflect an underlying genetic vulnerability shared between those risk factors and asthma.

Inhaled corticosteroids and decline of lung function in community residents with asthma.

BACKGROUND: Inhaled corticosteroids (ICS) constitute the cornerstone of treatment for asthma. Many studies have reported beneficial short term effects of these drugs, but there are few data on the long term effects of ICS on the decline in forced expiratory volume in 1 second (FEV(1)). This study was undertaken to determine whether adults with asthma treated with ICS have a less pronounced decline in FEV(1) than those not treated with ICS. METHODS: Two hundred and thirty four asthmatic individuals from a longitudinal epidemiological study of the general population of Copenhagen, Denmark were divided into two groups; 44 were treated with ICS and 190 were not treated with ICS. The annual decline in FEV(1) was measured over a 10 year follow up period. RESULTS: The decline in FEV(1) in the 44 patients receiving ICS was 25 ml/year compared with 51 ml/year in the 190 patients not receiving this treatment (p<0.001). The linear regression model with ICS as the variable of interest and sex, smoking, and wheezing as covariates showed that treatment with ICS was associated with a less steep decline in FEV(1) of 18 ml/year (p = 0.01). Adjustment for additional variables including age, socioeconomic status, body mass index, mucus hypersecretion, and use of other asthma medications did not change these results. CONCLUSIONS: Treatment with ICS is associated with a significantly reduced decline in ventilatory function.

Risk factors for rehospitalisation in COPD: role of health status, anxiety and depression.

The aim of the present study was to analyse the risk of rehospitalisation in patients with chronic obstructive pulmonary disease and associated risk factors. This prospective study included 416 patients from a university hospital in each of the five Nordic countries. Data included demographic information, spirometry, comorbidity and 12 month follow-up for 406 patients. The hospital anxiety and depression scale and St. George's Respiratory Questionnaire (SGRQ) were applied to all patients. The number of patients that had a re-admission within 12 months was 246 (60.6%). Patients that had a re-admission had lower lung function and health status. A low forced expiratory volume in one second (FEV1) and health status were independent predictors for re-admission. Hazard ratio (HR; 95% CI) was 0.82 (0.74-0.90) per 10% increase of the predicted FEV1 and 1.06 (1.02-1.10) per 4 units increase in total SGRQ score. The risk of rehospitalisation was also increased in subjects with anxiety (HR 1.76 (1.16-2.68)) and in subjects with low health status (total SGRQ score >60 units). When comparing the different subscales in the SGRQ, the closest relation between the risk of rehospitalisation was seen with the activity scale (HR 1.07 (1.03-1.11) per 4 unit increase). In patients with low health status, anxiety is an important risk factor for rehospitalisation. This may be important for patient treatment and warrants further studies.