Neonatal Vitamin D Status and Risk of Asthma in Childhood: Results from the D-Tect Study.

BACKGROUND: low vitamin D status in pregnancy can influence the offspring's lung function and contribute to childhood asthma development. The objective of this study was to examine the influence of neonatal vitamin D status on the development of asthma among children age 3-9 years in a large population sample. METHOD: in a case-cohort study utilizing a Danish biobank and register data we examined the association between neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentrations and incidence of asthma among children aged 3-9 years. Cases of asthma (n = 911) were randomly selected among all cases of asthma in the Danish National Patient Register from children born between 1992 and 2002. The sub-cohort (n = 1423) was randomly selected among all children born in the same period. We used a weighted Cox proportional hazard model assessing the hazard of first asthma diagnoses by quintiles of 25(OH)D3. RESULTS: the median 25(OH)D3 (interquartile range) for asthma cases was 23 nmol/L (14-35) and the sub-cohort 25 nmol/L (14-40). The hazard ratio for developing asthma between ages 3 and 9 years was lower for children in the fifth quintile of neonatal 25(OH)D3 compared to children in the first quintile, both in the unadjusted (0.61 95% CI: 0.46-0.80) and adjusted (0.55 95% CI: 0.39-0.77) analyses. CONCLUSION: the results from our study suggest that higher neonatal vitamin D concentration may reduce the risk of developing childhood asthma at ages 3-9 years, indicating that neonatal vitamin D status as a proxy of vitamin D status during the prenatal period is important for normal immune- and lung development.

Exposure to Vitamin D Fortification Policy in Prenatal Life and the Risk of Childhood Asthma: Results From the D-Tect Study.

Prenatal vitamin D insufficiency may be associated with an increased risk of developing childhood asthma. Results from epidemiological studies are conflicting and limited by short follow-up and small sample sizes. The objective of this study was to examine if children born to women exposed to the margarine fortification policy with a small dose of extra vitamin D during pregnancy had a reduced risk of developing asthma until age 9 years, compared to children born to unexposed women. The termination of a Danish mandatory vitamin D fortification policy constituted the basis for the study design. We compared the risk of inpatient asthma diagnoses in all Danish children born two years before (n = 106,347, exposed) and two years after (n = 115,900, unexposed) the termination of the policy. The children were followed in the register from 0-9 years of age. Data were analyzed using Cox proportional hazards regression. The Hazard Ratio for the first inpatient asthma admission among exposed versus unexposed children was 0.96 (95%CI: 0.90-1.04). When stratifying by sex and age, 0-3 years old boys exposed to vitamin D fortification showed a lower asthma risk compared to unexposed boys (HR 0.78, 95%CI: 0.67-0.92). Prenatal exposure to margarine fortification policy with extra vitamin D did not affect the overall risk of developing asthma among children aged 0-9 years but seemed to reduce the risk among 0-3 years old boys. Taking aside study design limitations, this could be explained by different sensitivity to vitamin D from different sex-related asthma phenotypes in children with early onset, and sex differences in lung development or immune responses.

Adherence and quality of life in adults and children during 3-years of SLIT treatment with Grazax-a real life study.

Respiratory allergic disease represents a global health problem, 30% of the population suffers from allergic rhinoconjunctivitis and 20% suffer from asthma. Allergy immunotherapy induce immunological tolerance and thereby modify the response to allergens and sublingual immunotherapy (SLIT) offers the possibility of home administration of allergen therapy, but adherence is more uncertain. The aim of the study was to investigate the adherence with GRAZAX in adults and children ≥ 5 years during three consecutive years of treatment. This was a non-interventional, prospective, observational, multi-center, open-label study to investigate adherence, quality of life, safety and tolerability of GRAZAX in adult and pediatric patients in a real-life setting. During the 3-years study period estimation of adherence was done regularly. Quality of life as well as symptom score was also assessed. In total, 399 patients (236 adults and 163 children) were included in the study. At baseline, 100% suffered from moderate-severe eyes and nose symptoms, and 31% had asthma in the grass pollen season. Overall, 55% completed a 3-years treatment period, whereas 37% stopped before end of study and 8% were lost to follow up. After 3 years, the adherence rate decreased from 98.2% (first month), 93.7% (first year), 93.2% (second year) and 88.9% (third year) and adverse events were the main reason for pre-term termination. The study suggests a good adherence to treatment in a real life setting among the patients finalizing 3-years SLIT therapy. The treatment was effective both on symptoms and HRQL.

Adverse Events During Immunotherapy Against Grass Pollen-Induced Allergic Rhinitis - Differences Between Subcutaneous and Sublingual Treatment.

Allergic rhinitis (AR) triggered by grass pollen is a common disease, affecting millions of people worldwide. Treatment consists of symptom-alleviating drugs, such as topical corticosteroids or antihistamines. Another option is potentially curative immunotherapy, currently available as sublingual and subcutaneous treatment. We investigated the potential differences in the prevalence and severity of adverse events related to subcutaneous and sublingual immunotherapy (SLIT) against grass pollen-induced AR. A thorough literature search was performed with PubMed and EMBASE. The findings were compared with the available summaries of product characteristics (SPC) and with commercial pharmacology databases (Micromedex). The majority of available safety data originate from registered products of standardized allergens. A surprisingly large percentage of drugs, especially those used in the United States, have no systematically collected safety data. No sufficiently powered randomized trials comparing sublingual and subcutaneous immunotherapy (SCIT) were available, but general safety assessments indicate that sublingual tablet treatment is safer than subcutaneous treatment. Not all commonly used immunotherapy drugs are officially registered, and not all have systematically collected safety data. This is especially true for older drugs used in the United States. In contrast, newer drugs that have undergone extensive clinical testing have better documentation, but unified collection of safety data is still lacking. Considering the evidence available, most drugs elicit similar side effects from the same organ systems, and symptoms from the sublingual drug classes are probably less severe. However, a head-to-head comparison of safety and efficacy is lacking.

Treatment of exercise-induced bronchoconstriction.

Exercise-induced bronchoconstriction (EIB) describes the transient narrowing of the airways during, and particularly after exercise and occurs commonly in asthmatic individuals. Limitation of exercise capacity is a frequent complaint in all age groups, and severity of EIB ranges from mild impairment of performance to severe bronchospasm and a large reduction in FEV1. Treatment of EIB varies from daily to less frequent therapy, depending on the level of activity. In this article, the authors evaluate the treatment possibilities before, during, and after exercise. They also review medications currently used to treat EIB.

Effects of mometasone, fluticasone, and montelukast on bone mineral density in adults with asthma.

BACKGROUND: Associations of inhaled corticosteroids (ICS) with bone mineral density (BMD) loss have not been characterized consistently. OBJECTIVE: This randomized, double-blind study assessed effects of mometasone furoate (MF) administered via dry powder inhaler on BMD of patients with persistent asthma. METHODS: Adults with mild-moderate persistent asthma who did not receive ICS for ≥3 months were randomized to MF 400 µg once daily (QD) in the evening (pm), MF 200 µg QD pm, montelukast sodium (ML) 10 mg QD pm, or fluticasone propionate (FP) 250 µg twice daily. Included patients had 25-hydroxy vitamin D levels ≥15 ng/mL at baseline. All the patients received calcium and vitamin D supplements for daily use during the trial. Duplicate BMD scans were done at baseline, 6 months, and 1 year. The mean percentage change in lumbar spine (LS) BMD from baseline to end point for MF 400 µg versus ML 10 mg was the primary analysis. Changes from baseline in left total femur BMD and femoral neck BMD were secondary assessments. RESULTS: At the end point, mean LS BMD increased 0.9% (MF 400 µg), 1.2% (ML), 0.7% (MF 200 µg), and 1.1% (FP), with no significant differences for MF 400 µg versus ML (-0.3% [95% CI, -1.01 to 0.27]) for LS BMD. No significant differences among treatments occurred for changes in left total femur BMD; all were slight increases. Changes in femoral neck BMD were 0.4% (MF 400 µg), -0.2% (ML), -0.2% (MF 200 µg), and -0.4% (FP); only the difference between MF 400 µg and FP was statistically significant (P = .044). CONCLUSION: No detrimental effects on lumbar BMD were observed after up to 1 year of treatment with MF in comparison with ML for patients who received calcium and vitamin D supplements.

Asthma in elite athletes: pathogenesis, diagnosis, differential diagnoses, and treatment.

Elite athletes have a high prevalence of asthma and exercise-induced bronchoconstriction. Although respiratory symptoms can be suggestive of asthma, the diagnosis of asthma in elite athletes cannot be based solely on the presence or absence of symptoms; diagnosis should be based on objective measurements, such as the eucapnic voluntary hyperpnea test or exercise test. When considering that not all respiratory symptoms are due to asthma, other diagnoses should be considered. Certain regulations apply to elite athletes who require asthma medication for asthma. Knowledge of these regulations is essential when treating elite athletes. This article is aimed at physicians who diagnose and treat athletes with respiratory symptoms. It focuses on the pathogenesis of asthma and exercise-induced bronchoconstriction in elite athletes and how the diagnosis can be made. Furthermore, treatment of elite athletes with asthma, anti-doping regulations, and differential diagnoses such as exercise-induced laryngomalacia are discussed.

Nonallergic rhinitis and its association with smoking and lower airway disease: A general population study.

BACKGROUND: The cause of nonallergic rhinitis (NAR) and its relation to lower airway disease remains unclear. The purpose of this study was to perform a descriptive analysis of the occurrence of rhinitis in a Danish general population with focus on NAR and its association with smoking and lower airway disease. METHODS: A population-based, cross-sectional study conducted in Copenhagen, Denmark was performed. A random sample from the general population (n = 7931; age, 18-69 years) was invited to a general health examination including measurements of serum-specific immunoglobulin E (IgE) to common aeroallergens; 3471 (44%) persons were accepted. For further analysis, we divided the population into the following groups: (I) negative specific IgE and no rhinitis (controls); (II) negative specific IgE and rhinitis (NAR); (III) positive specific IgE and rhinitis (allergic rhinitis [AR]); and (IV) positive specific IgE but no rhinitis (sensitized). RESULTS: We found that NAR was associated with asthma (odds ratio [OR] = 2.51 [1.87-3.37]); chronic bronchitis (OR = 2.27 [1.85-2.79]); current smoking (>15 g/day; OR = 1.57 [1.18-2.08]); lower forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) ratios and reduced FEV(1) values. The association with chronic bronchitis was stronger in NAR than in AR, whereas the opposite was true for asthma. FEV(1)/FVC of <70% was not significantly associated to any group. CONCLUSION: This epidemiological study indicates that both asthma and chronic bronchitis are important comorbidities in NAR confirming the "united airway" hypothesis, and that smoking might be a significant modulator of disease. Although NAR was significantly associated with poor lung function, no significant association with chronic obstructive pulmonary disease was shown.

Early detection of COPD in primary care--the Copenhagen COPD Screening Project.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is among the leading causes of death in the world, and further increases in the prevalence and mortality are predicted. Delay in diagnosing COPD appears frequently even though current consensus guidelines emphasize the importance of early detection of the disease. The aim of the present study is to evaluate the effectiveness of a screening programme in general practice. METHODS/DESIGN: Subjects aged 65 years and older registered with a General Practitioner (GP) in the eastern Copenhagen will receive a written invitation and a simple questionnaire focusing on risk factors and symptoms of COPD. Subjects who meet the following criteria will be encouraged to undergo spirometric testing at their GP: current smokers, former smokers, and subjects with no smoking history but who have dyspnea and/or chronic cough with sputum. DISCUSSION: The Copenhagen COPD Screening Project evaluates the effectiveness of a two-stage screening program for COPD in general practice and provides important information on how to organize early detection of COPD in general practice in the future.