Background: Vitamin D deficiency has been associated with markers for allergy and asthma severity in children with asthma. However, its association with Chinese adult asthmatics has not been studied. Objective: To examine whether vitamin D status is associated with lung function and total serum IgE in Chinese adults with newly diagnosed asthma. Methods: We conducted a cross-sectional study including 435 Chinese patients aged >18 years with newly diagnosed asthma. Vitamin D status was assessed by measuring serum 25 hydroxyvitamin D (25OHD) concentrations. The primary outcomes included airflow limitation, as measured by the forced expiratory volume in 1 s (FEV₁), FEV₁ % predicted, and FEV₁/forced vital capacity (FVC), and serum total IgE concentration. Results: Vitamin D deficiency was prevalent in Chinese adults with asthma, with 88.9% of the subjects having 25OHD <50 nmol/l. Serum 25OHD concentration was positively correlated with FEV₁ % predicted (p = 0.02, r = 0.12). After adjusting for age, sex, body mass index, smoking, month of blood collection, and symptom duration, we found significant positive associations between 25OHD concentrations and FEV₁ (in liters), FEV₁ % predicted, and FEV₁/FVC (p for trend < 0.05 for all). The adjusted odds ratios for the highest versus the lowest 25OHD quartile were 0.50 (0.26–0.96) for FEV₁ <75% predicted and 0.44 (0.20–0.95) for FEV₁/FVC% <0.75. There was no significant association between 25OHD concentrations and total IgE. Conclusions: Vitamin D deficiency was highly prevalent in Chinese asthma patients, and vitamin D status was associated with lung function.

Metabolites of arachidonic acid such as prostacyclin (PGI2) have been shown to participate in the pathogenesis of pulmonary fibrosis by inhibiting the expression of pro-inflammatory and pro-fibrotic mediators. In this investigation, we examined whether iloprost, a stable PGI2 analogue, could prevent bleomycin-induced pulmonary inflammation and fibrosis in a mouse model. Mice received a single intratracheal injection of bleomycin with or without intraperitoneal iloprost. Pulmonary inflammation and fibrosis were analysed by histological evaluation, cellular composition of bronchoalveolar lavage (BAL) fluid, and hydroxyproline content. Lung mechanics were measured. We also analysed the expression of inflammatory mediators in BAL fluid and lung tissue. Administration of iloprost significantly improved survival rate and reduced weight loss in the mice induced by bleomycin. The severe inflammatory response and fibrotic changes were significantly attenuated in the mice treated with iloprost as shown by reduction in infiltration of inflammatory cells into the airways and pulmonary parenchyma, diminution in interstitial collagen deposition, and lung hydroxyproline content. Iloprost significantly improved lung static compliance and tissue elastance. It increased the expression of IFNγ and CXCL10 in lung tissue measured by RT-PCR and their levels in BAL fluid as measured by ELISA. Levels of TNFα, IL-6 and TGFβ1 were lowered by iloprost. Iloprost prevents bleomycin-induced pulmonary fibrosis, possibly by upregulating antifibrotic mediators (IFNγ and CXCL10) and downregulating pro-inflammatory and pro-fibrotic cytokines (TNFα, IL-6, and TGFβ1). Prostacyclin may represent a novel pharmacological agent for treating pulmonary fibrotic diseases.

Background: Asthma is a genetically heterogeneous disease. Polymorphisms of genes encoding components of the vitamin D pathway have been reported to associate with the risk of asthma. We have previously demonstrated that vitamin D status was associated with lung function in Chinese asthma patients. In this study, we tested whether polymorphisms of genes encoding for vitamin D receptor (VDR), vitamin D 25-hydroxylase (CYP2R1) and vitamin D binding protein (GC) were associated with asthma in the Chinese Han population. Methods: We sequenced all 8 exons of VDR and all 5 exons of CYP2R1 in a Chinese case-control cohort of asthma consisting of 467 cases and 288 unrelated healthy controls. Two mutations were identified in these regions. These variants were specified as rs2228570 in exon 2 of VDR and rs12794714 in exon 1 of CYP2R1. We also genotyped two common polymorphisms in GC gene (rs4588 and rs7041) by a PCR-restriction fragment length polymorphism (RFLP) method. We analyzed the association between these 4 polymorphisms and asthma susceptibility and asthma-related traits. Results: Polymorphic markers in VDR and CYP2R1 were not associated with asthma in the Chinese Han cohort. Importantly, variants in GC gene, which give rise to the two most common electrophoretic isoforms of the vitamin D binding protein, were associated with asthma susceptibility. Compared with isoform Gc1, Gc2 was significantly associated with the risk of asthma (OR = 1.35, 95% CI = 1.01-1.78 p = 0.006). Conclusions: The results provide supporting evidence for association between GC variants and asthma susceptibility in the Chinese Han population.

Nanoparticles have become a key technology in multiple industries. However, there are growing reports of the toxicity of nanomaterials to humans. In particular, nanomaterials have been linked to lung diseases. The molecular mechanisms of nanoparticle toxicity are largely unexplored. Acute lung injury was induced in wild-type mice and angiotensin-coverting enzyme 2 (ACE2) knockout mice by the intratracheal instillation of cationic polyamidoamine dendrimer (PAMAM) nanoparticles. For rescue experiments, losartan (15 mg/kg in PBS) was injected intraperitoneally 30 min before nanoparticle administration. Some PAMAM nanoparticles, but not anionic PAMAM nanoparticles or carbon nanotubes, triggered acute lung failure in mice. Mechanistically, cationic nanoparticles can directly bind ACE2, decrease its activity and down-regulate its expression level in lung tissue, resulting in deregulation of the renin-angiotensin system. Gene inactivation of Ace2 can exacerbate lung injury. Importantly, the administration of losartan, which is an angiotensin II type I receptor antagonist, can ameliorate PAMAM nanoparticle-induced lung injury. Our data provide molecular insight into PAMAM nanoparticle-induced lung injury and suggest potential therapeutic and screening strategies to address the safety of nanomaterials.