VDR Gene Polymorphisms and Allergic Diseases: Evidence from a Meta-analysis.

Associations between vitamin D receptor (VDR) gene polymorphisms and allergic diseases were already reported by many publications. The aim of this meta-analysis was to clarify associations between VDR gene polymorphisms and allergic diseases by combing the results of all relevant publications. Eligible publications were searched from Pubmed, Embase, WOS and CNKI. We used Review Manager to combine the results of individual studies. Twenty-one studies were included in this study. Combined results proved that VDR rs1544410 BsmI (over-dominant comparison: p = .04, OR = 1.14, 95% CI 1.01-1.29; allele comparison: p = .03, OR = 1.11, 95% CI 1.01-1.22) and rs731236 TaqI (dominant comparison: p = .01, OR = 1.18, 95% CI 1.04-1.33) polymorphisms were both associated with allergic diseases. In subgroup analyses by type of disease, we confirmed positive results for rs1544410 BsmI polymorphism in both asthma and atopic dermatitis, and for rs731236 TaqI polymorphism in atopic dermatitis. Besides, in subgroup by ethnicity of participants, we observed significant associations with allergic diseases for rs7975232 ApaI polymorphism in Caucasians, for rs1544410 BsmI polymorphism in Asians and Caucasians, and for rs731236 TaqI polymorphism in Asians. We also investigated associations between VDR rs2228570 FokI polymorphism and allergic diseases, yet no any positive results were detected for this polymorphism. If we only focused on asthma, then positive findings were detected for rs1544410 BsmI polymorphism in Caucasians, and for rs731236 TaqI polymorphism in Asians. Collectively, this meta-analysis proved that VDR rs7975232 ApaI, rs1544410 BsmI and rs731236 TaqI gene polymorphisms may confer susceptibility to allergic diseases in certain populations.

Klotho Reduction in Alveolar Macrophages Contributes to Cigarette Smoke Extract-induced Inflammation in Chronic Obstructive Pulmonary Disease.

Abnormal inflammation and accelerated decline in lung function occur in patients with chronic obstructive pulmonary disease (COPD). Klotho, an anti-aging protein, has an anti-inflammatory function. However, the role of Klotho has never been investigated in COPD. The aim of this study is to investigate the possible role of Klotho by alveolar macrophages in airway inflammation in COPD. Klotho levels were assessed in the lung samples and peripheral blood mononuclear cells of non-smokers, smokers, and patients with COPD. The regulation of Klotho expression by cigarette smoke extract (CSE) was studied in vitro, and small interfering RNA (siRNA) and recombinant Klotho were employed to investigate the role of Klotho on CSE-induced inflammation. Klotho expression was reduced in alveolar macrophages in the lungs and peripheral blood mononuclear cells of COPD patients. CSE decreased Klotho expression and release from MH-S cells. Knockdown of endogenous Klotho augmented the expression of the inflammatory mediators, such as MMP-9, IL-6, and TNF-α, by MH-S cells. Exogenous Klotho inhibited the expression of CSE-induced inflammatory mediators. Furthermore, we showed that Klotho interacts with IκBα of the NF-κB pathway. Dexamethasone treatment increased the expression and release level of Klotho in MH-S cells. Our findings suggest that Klotho plays a role in sustained inflammation of the lungs, which in turn may have therapeutic implications in COPD.

Bronchial epithelial cells: The key effector cells in the pathogenesis of chronic obstructive pulmonary disease?

The primary function of the bronchial epithelium is to act as a defensive barrier aiding the maintenance of normal airway function. Bronchial epithelial cells (BEC) form the interface between the external environment and the internal milieu, making it a major target of inhaled insults. However, BEC can also serve as effectors to initiate and orchestrate immune and inflammatory responses by releasing chemokines and cytokines, which recruit and activate inflammatory cells. They also produce excess reactive oxygen species as a result of an oxidant/antioxidant imbalance that contributes to chronic pulmonary inflammation and lung tissue damage. Accumulated mucus from hyperplastic BEC obstructs the lumen of small airways, whereas impaired cell repair, squamous metaplasia and increased extracellular matrix deposition underlying the epithelium is associated with airway remodelling particularly fibrosis and thickening of the airway wall. These alterations in small airway structure lead to airflow limitation, which is critical in the clinical diagnosis of chronic obstructive pulmonary disease (COPD). In this review, we discuss the abnormal function of BEC within a disturbed immune homeostatic environment consisting of ongoing inflammation, oxidative stress and small airway obstruction. We provide an overview of recent insights into the function of the bronchial epithelium in the pathogenesis of COPD and how this may provide novel therapeutic approaches for a number of chronic lung diseases.

Asthma and toxocariasis.

BACKGROUND: Asthma is the most common chronic disease in children and a major public health problem in adults. A relation between asthma and toxocariasis has been hypothesized. OBJECTIVE: To evaluate the strength of association between asthma and Toxocara species seropositivity by conducting a systematic review and a meta-analysis of available data. METHODS: PubMed, EMBASE, Web of Science, and the reference lists of all relevant articles and books were screened until October 2013. Two authors independently assessed eligibility and study quality and extracted data. A common odds ratio was estimated using a random-effects meta-analysis model of aggregated published data. RESULTS: Ten studies met the inclusion criteria, for a total of 1,530 participants (723 cases and 807 controls). This meta-analysis found a significantly higher prevalence of Toxocara canis infection in patients with asthma than in controls (odds ratio 3.36, 95% confidence interval 1.76-6.42, P < .001). Similar results were found when meta-analysis was restricted to the studies considering only children or adults. CONCLUSION: The results support the existence of a positive association between asthma and Toxocara species seropositivity.

Interventions to reduce individual exposure of elderly individuals and children to haze: a review.

Given rapid economic developments and urbanization over the last few decades, China has experienced frequent haze episodes, which have adverse effects on public health. Children and elderly individuals are more susceptible than the general population to air pollution. In this study, we introduce interventions to reduce the exposure of elderly individuals and children to air pollution during hazy weather. These interventions include avoiding outdoor activities, wearing a dust mask, reducing burning biomass fuels, reducing frying and smoking at home, using an air filtration unit and taking supplemental antioxidants. However, the actual benefits of these measures remain unproven and are unlikely to be adequate. Sustained clean air policies remain the most important and efficient solution to reduce air pollution-related health effects.