Letter to the editor

Age- and atopy-dependent effects of vitamin D on wheeze and asthma

Previous studies, mostly with children, have reported inconsistent findings on the associations of vitamin D status with asthma prevalence, exacerbations, and control. Because of limited research with adults, we examined these associations in a large community-based sample of New Zealand adults.

5110 participants, aged 50–84 years, were recruited from the community into a clinical trial of vitamin D supplementation. The current analysis is based on baseline blood sample collection to measure serum 25-hydroxyvitamin D (25(OH)D), which was deseasonalized for data analyses; and baseline asthma assessment, which included questions on asthma prevalence, urgent medical care for asthma in the previous 12 months, and control of asthma symptoms in the previous 4 weeks.

702 (13.2%) of 5088 participants reported having doctor-diagnosed asthma. There was no difference in mean (SE) 25(OH)D concentration between participants with and without asthma: 66 (0.9) and 66 (0.4) nmol/L, respectively, adjusting for sex (p = 0.71). However, in multivariable analyses restricted to participants who reported having asthma, mean (SE) 25(OH)D concentration was 6.3 (2.6) nmol/L lower in those who reported having urgent medical care for asthma in the previous 12 months compared to others (p = 0.02), and 10.4 (3.9) nmol/L lower in those with very poor asthma control compared to those who were well-controlled (p = 0.03).

These cross-sectional results suggest that asthmatic adults with lower vitamin D status are more likely to receive urgent asthma medical care and to experience poor asthma control. Clinical trials are needed to determine the role of vitamin D supplementation in asthma management.

A role of vitamin D in the development of respiratory and allergic disease in children remains unclear. It may be likely that vitamin D has an effect on airway inflammation, but only few studies examined the effect in children. We aimed to examine whether serum 25-hydroxyvitamin D (25(OH) vitamin D) concentrations are associated with the fraction of exhaled nitric oxide (FeNO), airway interrupter resistance (Rint), physician diagnosed asthma ever, wheezing and eczema in a population-based cohort study in 6 year old children.

Serum 25(OH) vitamin D concentration was assessed in 3815 children. 25(OH) vitamin D concentrations ≥75 nmol/L were considered as sufficient, between 50 and 75 nmol/L as insufficient, and <50 nmol/L as deficient. FeNO and Rint were measured at the research center. Data on physician diagnosed asthma, wheezing, and eczema were obtained by parent-reported questionnaires.

In comparison with sufficient 25(OH) vitamin D concentration, deficient concentrations were associated with elevated FeNO of ≥25 ppb (OR: 2.54; 95% CI: 1.34–4.80). In addition, deficient and insufficient 25(OH) vitamin D concentrations were associated with a lower Rint (Z-score: −1.26; 95% CI: −1.66 to −0.85) (ß: −0.75; 95% CI: −1.08 to −0.42), and increased risks of eczema (OR: 1.65; 95% CI: 1.13–2.41) (OR: 1.44; 95% CI: 1.06–1.95). Insufficient 25(OH) vitamin D concentration were associated with a decreased risk of physician diagnosed asthma ever (OR: 0.59; 95% CI: 0.38–0.94).

Our results indicate that lower 25(OH) vitamin D levels are associated with elevated FeNO levels, but lower Rint values. Lower 25(OH) vitamin D levels are also associated with a decreased risk for asthma diagnoses but an increased risk for eczema.

Endotoxin has been shown to induce neutrophilic asthma and wheeze after binding toll-like receptor 4 to produce pro-inflammatory cytokines. Animal models have demonstrated that vitamin D might inhibit lipopolysaccharide-induced cytokines. However, whether endotoxin exposure and serum vitamin D deficiency interact to affect asthma and wheeze in humans has never been investigated in an epidemiological study.

Joint associations of house dust endotoxin and vitamin D with asthma and wheeze were examined using logistic regression adjusted for covariates in 5924 US participants of the National Health and Nutrition Examination Survey (NHANES). Interactions were assessed on the multiplicative as well as additive scale using the relative excess risk, the attributable portion due to additive interaction, and the synergy index.

The median endotoxin concentration was 19.1 EU/mg. Prevalence of vitamin D inadequacy (20–30 ng/ml) and deficiency (<20 ng/ml) were respectively 42.9 and 33.4%. The combination of high endotoxin and low vitamin D was associated with current asthma (OR: 1.56, 95% CI: 1.09, 2.23), wheeze in the past 12 months (OR: 1.72, 95% CI: 1.10, 3.71), recurrent wheeze (OR: 1.97, 95% CI: 1.00, 4.00), asthma diagnosis or recurrent wheeze (OR: 1.88, 95% CI: 1.33, 2.66), and current asthma or recurrent wheeze (OR:1.81, 95% CI: 1.23, 2.68) when compared to low endotoxin and normal vitamin D. The interactions between the exposures were not significant on the multiplicative or additive scale for any of the outcomes.

Combination of high endotoxin exposure and low vitamin D increases the odds of asthma and wheeze, but the exposures do not interact or modify each other's effect in the NHANES cohort.

Vitamin D deficiency (VDD) is highly prevalent worldwide, with adverse effects on bone health but also potentially other unfavorable consequences. VDD and asthma-incidence/severity share many common risk factors, including winter season, industrialization, poor diet, obesity, dark skin pigmentation, and high latitude. Multiple anatomical areas relevant to asthma contain both the enzyme responsible for producing activated vitamin D and the vitamin D receptor suggesting that activated vitamin D (1,25-dihydroxyvitamin D) may have important local effects at these sites.

Emerging evidence suggests that VDD is associated with increased airway hyperresponsiveness, decreased pulmonary function, worse asthma control, and possibly decreased response to standard anti-asthma therapy. However the effect is inconsistent with preliminary evidence from different studies suggesting vitamin D is both beneficial and detrimental to asthma genesis and severity.

Current evidence suggests that supplementation with moderate doses of vitamin D may be appropriate for maintenance of bone health in asthmatics, particularly steroid users. However emerging data from an increasing number of randomized, controlled, intervention studies of vitamin D supplementation in pediatric and adult asthma are becoming available and should help determine the importance, if any of vitamin D for asthma pathogenesis.

The purpose of this second of a two-part review is to review the current human literature on vitamin D and asthma, discussing the possible consequences of VDD for asthma and the potential for vitamin D repletion as adjunct therapy.

The United Kingdom (UK) has one of the highest prevalence of asthma in the world, which represents a significant economic and societal burden. Reduced ventilation resulting from increased energy efficiency measures acts as a modifier for mould contamination and risk of allergic diseases. To our knowledge no previous study has combined detailed asset management property and health data together to assess the impact of household energy efficiency (using the UK Government's Standard Assessment Procedure) on asthma outcomes in an adult population residing in social housing.

Postal questionnaires were sent to 3867 social housing properties to collect demographic, health and environmental information on all occupants. Detailed property data, residency periods, indices of multiple deprivation (IMD) and household energy efficiency ratings were also investigated. Logistic regression was used to calculate odds ratios and confidence intervals while allowing for clustering of individuals coming from the same location.

Eighteen percent of our target social housing population were recruited into our study. Adults had a mean age of 59 (SD ± 17.3) years and there was a higher percentage of female (59%) and single occupancy (58%) respondents. Housing demographic characteristics were representative of the target homes. A unit increase in household Standard Assessment Procedure (SAP) rating was associated with a 2% increased risk of current asthma, with the greatest risk in homes with SAP > 71. We assessed exposure to mould and found that the presence of a mouldy/musty odour was associated with a two-fold increased risk of asthma (OR 2.2 95%; CI 1.3–3.8). A unit increase in SAP led to a 4–5% reduction in the risk of visible mould growth and a mouldy/musty odour.

In contrast to previous research, we report that residing in energy efficient homes may increase the risk of adult asthma. We report that mould contamination increased the risk of asthma, which is in agreement with existing knowledge. Exposure to mould contamination could not fully explain the association between increased energy efficiency and asthma. Our findings may be explained by increased energy efficiency combined with the provision of inadequate heating, ventilation, and increased concentrations of other biological, chemical and physical contaminants. This is likely to be modified by a complex interaction between occupant behaviours and changes to the built environment. Our findings may also be confounded by our response rate, demographic and behavioural differences between those residing in low versus high energy efficient homes, and use of self-reported exposures and outcomes.

Energy efficiency may increase the risk of current adult asthma in a population residing in social housing. This association was not significantly modified by the presence of visible mould growth, although further research is needed to investigate the interaction between other demographic and housing characteristic risk factors, especially the impact of fuel poverty on indoor exposures and health outcomes.

A multidisciplinary approach is required to assess the interaction between energy efficiency measures and fuel poverty behaviours on health outcomes prior to the delivery of physical interventions aimed at improving the built environment. Policy incentives are required to address fuel poverty issues alongside measures to achieve SAP ratings of 71 or greater, which must be delivered with the provision of adequate heating and ventilation strategies to minimise indoor dampness. Changes in the built environment without changes in behaviour of domicile residents may lead to negative health outcomes.

Vitamin D has immune modulatory functions, and thus its relationship with allergic disease has been evaluated in a number of studies. However, no concrete link between serum IgE level and vitamin D has been established. Thus, the purpose of study was to confirm the association of serum vitamin D level with the serum IgE (total and Dematophagoides farinae specific IgE) in Korean adolescents.

A total of 365 subjects between 10 and 18 years of age were enrolled through the Korea National Health and Nutrition Examination Survey (KNHANES). Serum levels of vitamin D, total IgE, and Dermatophagoides farinae (Df) specific IgE were measured, and data for potential confounding variables were collected. Multivariate regression analyses were used to determine the independent effects of these variables.

Levels of both total and Df specific IgE were positively correlated with serum concentration of vitamin D (Spearman's rho (R) = 0.126, p = 0.016; R = 0.152, p = 0.004, respectively). These results were confirmed by multivariate linear regression analysis after adjusting for sex, age, and body mass index (coefficient (B): 10.45 95% confidence interval (CI): 0.59–20.31; B: 1.06, 95% CI: 0.31–1.80, respectively). And, the association between serum vitamin D and IgE showed the different results depending on the presence or absence of Df sensitization.

Serum concentration of vitamin D was positively associated with levels of both total IgE and Df-specific IgE in Korean adolescents.