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Background A small percentage of asthma patients experience severe and refractory asthma that responds poorly to standard therapy. However, this percentage is increasing and better treatment options are therefore needed. Our previous study showed that cultured human airway smooth muscle cells treated with IL-13 R130Q, a naturally occurring IL-13 variant, displayed enhanced functional activities compared to wild-type (WT) IL-13. The present study aims to determine whether IL-13 R130Q could modulate the ASMC phenotype to further contribute to severe asthma. Methods Human bronchial smooth muscle cells (hBSMCs) were treated with increasing concentrations of IL-13R130Q or WT IL-13 for 24 h. Endogenous expressions of IL-5 and IL-4 were characterized with Enzyme-linked immunosorbent assay analysis. Acetylcholine-induced changes in intracellular calcium concentration were analyzed with the fluorescent probe Fluo-3/AM with flow-cytometric analysis. Cell proliferation was quantified using the CCK-8 kit and cell migration using the Boyden chamber assay. Results IL-13 R130Q induced significantly higher levels of proliferation, migration, and contraction, as well as secretion of IL-4 and IL-5 in hBSMCs compared to WT IL-13. Conclusions Taken all together, our data indicate that IL-13R130Q may contribute to severe asthma through phenotypic modulation of hBSMCs.

Additional file 1. Supplemental Tables and Figure of household mold exposure interacts with inflammation-related genetic variants on childhood asthma.

Additional file 2. The role of the SNPs in the inflammation process of asthma.

Hand, foot, and mouth disease (HFMD) is a common infectious disease in childhood caused by an enterovirus (EV), and which is principally seen in children under 5 years of age. To promote diagnostic awareness and effective treatments, to further standardize and strengthen the clinical management and to reduce the mortality of HFMD, the guidelines for diagnosis and treatment have been developed. National Health Commission of China assembled an expert committee for a revision of the guidelines. The committee included 33 members who are specialized in diagnosis and treatment of HFMD. Early recognition of severe cases is utmost important in diagnosis and treatment of patients with HFMD. The key to diagnosis and treatment of severe cases lies in the timely and accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to stage 4. Clinicians should particularly pay attention to those EV-A71 cases in children aged less than 3 years, and those with disease duration less than 3 days. The following indicators should alert the clinician of possible deterioration and impending critical disease: (1) persistent hyperthermia; (2) involvement of nervous system; (3) worsening respiratory rate and rhythm; (4) circulatory dysfunction; (5) elevated peripheral WBC count; (6) elevated blood glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be treated as outpatients. Patients should be isolated to avoid cross-infection. Intense treatment modalities should be given for those severe cases. The guidelines can provide systematic guidance on the diagnosis and management of HFMD.

Background: Research increasingly suggests that asthma is a familial and hereditary disorder and that genetic and environmental factors play a key role in its pathogenesis. Objective: The aim of this study was to investigate the associations between 10 single nucleotide polymorphism (SNP) loci in the development of asthma in children from the Mauritian population. Methods: The study population consisted of 193 children with asthma and 189 healthy controls from the Mauritian population. Asthma was diagnosed in accordance with the American Thoracic Society criteria. TaqMan real-time quantitative polymerase chain reaction was used to detect the genotypes of the SNP loci. Results: No statistically significant differences (p>0.05) were found between the experimental and control group in genotype distribution among nine of the loci (MS4A2 E237G, MS4A2 C-109T, ADRB2 R16G, IL4RA Q551R, IL4RA I75V, IL4 C-590T, IL13 A2044G, IL13 C-1112T, and CHI3L1 C-131G). However, the frequency of IL13 C1923T TT in the asthma gro...

Over the past 30 years, China has enjoyed rapid economic development along with urbanization at a massive scale that the world has not experienced before. Such development has also been associated with a rapid rise in the prevalence of allergic disorders. Because of the large childhood population in the country, the burden of childhood allergic disorders has become one of the major challenges in the healthcare system. Among the Chinese centers participating in the International Study of Asthma and Allergies in Childhood, the data clearly showed a continuing rise in the prevalence of asthma, allergic rhinitis, and atopic eczema. However, the discipline of pediatric allergy in mainland China is still in its infancy due to the lack of formal training program and subspecialty certification. Clinicians and researchers are increasingly interested in providing better care for patients with allergies by establishing pediatric allergy centers in different regions of the country. Many of them have also participated in national or international collaborative projects hoping to answer the various research questions related to the discipline of pediatric allergy and immunology. It is our hope that the research findings from China will not only improve the quality of care of affected children within this country but also the millions of patients with allergies worldwide.

Objective: To investigate the serum expressions of chemokines CCL2 and CCL3 in patients with rheumatoid arthritis (RA) who were treated with recombinant human interleukin 1 (IL-1) receptor antagonist (IL-1Ra). Material and methods: Serum CCL2 and CCL3 were determined using an enzyme-linked immunosorbent assay in 54 active RA patients before and after treatment with IL-1Ra or a placebo, as well as 36 healthy controls. Results: Compared with the healthy controls, all the 54 RA patients exhibited higher serum CCL2 and CCL3 before and after treatment (p < 0.05). However, patients who had a good response to IL-1Ra treatment had significantly lower mean changes in the serum CCL2 and CCL3 levels from baseline to the last injection than IL-1Ra non-responders (p < 0.01). Conclusions: CCL2 and CCL3 may be useful efficacy markers of IL-1Ra treatment.

Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 × 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 × 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 × 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis.

To investigate the relationship of pathogen DNA copies with clinic and laboratory features among children with Mycoplasma pneumoniae (MP) pneumonia.A total of 95 enrolled children with MP pneumonia were assigned into the high-MP-load group (10Compared with the low-MP-load group, 72.7% in the high-MP-load group developed refractory MP pneumonia who failed to respond to at least 1-week treatment with macrolides (72.7% vs 41.9%, P = 0.005). More children in the high-load group than those in the low-load group presented with extrapulmonary manifestations, lung consolidation, pleural effusion and atopic conditions including any allergy history, positive findings of aeroallergen test and increased serum IgE and ECP (P 0.05). A significant higher BALF IL-4 level was seen in the high-load group versus the low-load group (23.00 ± 11.24 vs 14.68 ± 7.12; pg/mL; P 0.01). There were no significant differences in BALF levels of IFN-γ, IL-8 and TNF-α between the two groups (P 0.05).Atopy may be a risk factor for the presence and severity of refractory MP pneumonia due to the high pathogen load in airway.

IL13, IL4, IL4RA, FCER1B, and ADRB2 are important inflammatory genes associated with immunoglobulin E levels. This study attempts to determine whether there are gene-gene interactions in the five genes among asthmatic children of Chinese Han nationality.Nine single-nucleotide polymorphisms (SNPs) in the five genes were genotyped in 1,000 asthmatic children and 1,000 healthy controls using TaqMan real-time quantitative polymerase chain reaction. Multifactor-dimensionality reduction method was applied for the analysis.A four-way gene-gene interaction model consisting of IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 was chosen as the optimal one for determining asthma susceptibility (testing balanced accuracy = 0.6089, cross-validation consistency = 10/10, P = 6.98E-05). Each of the four SNPs was identified to have an independent association with childhood asthma (G allele of rs20541, odds ratio (OR) = 1.24, P = 1.23E-03; T allele of rs2243250, OR = 1.25, P = 3.81E-03; A allele of rs1042713, OR = 1.29, P = 6.75E-05; G allele of rs569108, OR = 1.27, P = 3.86E-03). Individuals homozygous for the risk alleles at all the four loci (rs20541 GG, rs2243250 TT, rs1042713 AA, and rs569108 GG) had a significantly higher risk of asthma compared with those without any risk homozygotes (OR = 13.55, P = 4.28E-03), and also greater than those with less than four risk homozygotes (OR = 10.09, P = 6.51E-03).Our results suggest that IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108, four SNPs with significant sole effect on asthma, interact to confer a higher risk for the disease in Chinese Han children.

Respiratory syncytial virus-induced bronchiolitis has been linked to the development of allergy and atopic asthma. IL-12 and possibly IL-18 are central mediators orchestrating Th1 and/or Th2 immune responses to infection. To determine a possible role for IL-12 in regulating the immune response to acute respiratory syncytial virus infection, IL-12p40 gene-targeted (IL-12p40−/−) and wild-type mice were intratracheally infected with respiratory syncytial virus, and lung inflammatory and immune responses were assessed. Lung inflammation and mucus production were increased in the airways of IL-12p40−/− mice as compared with those of wild-type mice, concurrent with increased levels of the Th2 effector cytokines IL-5 and IL-13. Respiratory syncytial virus clearance and levels of Th1 effector cytokine IFN-γ were not altered. Interestingly, IL-18, another mediator of IFN-γ production, was significantly increased in the lungs of IL-12p40−/− mice early during the course of infection. Abrogation of IL-18-mediated signaling in IL-12p40−/− mice further enhanced Th2 immune response and mucus production in the airways during respiratory syncytial virus infection but failed to modulate IFN-γ production or viral clearance. These findings implicate a role for IL-12 and IL-18 in modulating respiratory syncytial virus-induced airway inflammation distinct from that of viral clearance.

Clara cell secretory protein (CCSP) has been shown to have anti-inflammatory and immunomodulatory functions in the lung. Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants and young children. RSV usually infects small airways and likely interacts with the Clara cells of bronchioles. To determine a possible role for CCSP during acute RSV infection, CCSP-deficient (CCSP−/−) and wild-type (WT) mice were intratracheally infected with RSV and the lung inflammatory and immune responses to RSV infection were assessed. RSV-F gene expression was increased in the lungs of CCSP−/− mice as compared with WT mice following RSV infection, consistent with increased viral persistence. Lung inflammation was significantly increased in CCSP−/− mice as compared with WT mice after infection. Moreover, although the levels of Th1 cytokines were similar, the levels of Th2 cytokines and neutrophil chemokines were increased in the lungs of CCSP−/− mice following infection. Physiologic endpoints of exacerbated lung disease, specifically airway reactivity and mucus production, were increased in CCSP−/− mice after RSV infection. Importantly, restoration of CCSP in the airways of CCSP−/− mice abrogated the increased viral persistence, lung inflammation, and airway reactivity. These findings suggest a role for CCSP and Clara cells in regulating lung inflammatory and immune responses to RSV infection.

Aim To evaluate the efficacy of tumor necrosis factor inhibitor infliximab in patients with rheumatoid arthritis (RA) who were disease-resistant to recombinant human interleukin-1 receptor antagonist (IL-1Ra). Methods A total of 104 patients with active RA despite methotrexate (MTX) treatment were enrolled in the open trial. Among them, 27 IL-1Ra nonresponders ‘Switchers’ and 51 biologic-naive patients ‘Naivers’ received an infusion of 3 mg/kg infliximab at weeks 0, 2, 6 and 14, combined with concurrent MTX therapy, while the other 26 patients who had never received any biologics ‘Controls’ continued MTX monotherapy. Clinical outcomes and safety were assessed at weeks 0, 2 and every 4 weeks thereafter for 18 weeks with the American College of Rheumatology (ACR) core set criteria, the Disease Activity Score in 28 joints, and records of adverse events (AEs) and abnormal laboratory findings. Results At week 18, an ACR20 response was achieved in 56% of Switchers and 61% of Naivers, compared with 23% of Controls (P = 0.0013 and 0.0126, respectively). Compared with Controls, both Switchers and Naivers achieved a significant improvement in tender-joint count, swollen-joint count, patient's assessment of pain, patient's and physician's global assessment of disease activity, erythrocyte sedimentation rate and C-reactive protein. Switchers even achieved a greater benefit from health assessment questionnaire (HAQ) scores than Naivers. Infliximab was well tolerated, with a similar incidence of AEs across all study groups. Conclusion Switching from IL-1Ra to infliximab is effective in improving disease activity and maintaining joint function.

The objective of this study is to assess the prevalence and risk in patients with juvenile onset ankylosing spondylitis (JoAS) complicated with low bone mineral density (BMD). A total of 112 children and adolescents with JoAS were enrolled in the study. Bone mass was measured from the lumbar spine and the left proximal femur using dual-energy X-ray absorptiometry. According to the 2007 International Society of Clinical Densitometry definitions, a Z score of less than −2 was termed as “low BMD.” Stepwise regression analysis was used to investigate associations between low BMD and disease-related factors including gender, age, weight, height, body mass index, disease duration, HLA-B27 antigen, grades of sacroiliitis, Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), patient global assessment (PGA), spine pain, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Low BMD was found in 18 (16.1 %) cases in at least one of the two measured regions. Lumbar spine BMD had negative correlations with BASDAI, BASFI, spine pain, ESR, and CRP (P < 0.05). Hip BMD significantly negatively correlated with BASDAI and PGA (P < 0.05). In conclusion, patients with JoAS are likely to develop low BMD, which may be related to high disease activity.

To compare tulobuterol patch and oral salbutamol sulfate in terms of efficacy and safety in children with mild or moderate acute attack of bronchial asthma.A total of 92 children with mild and moderate acute asthmatic attack were randomly divided into salbutamol group (n=46) and tulobuterol group (n=46). Both groups received routine treatment with antihistamine, selective leukotriene receptor antagonist and glucocorticoid. In addition, the salbutamol group was given slow-release capsules of salbutamol sulfate, and the tulobuterol group was treated with tulobuterol patch. The two groups were compared with respect to symptom scores of cough, wheeze, respiratory rate, wheezing sound, three depression sign and peak expiratory flow, as well as adverse events.As the treatment proceeded, symptom scores decreased in both groups; on the third day of treatment, all symptom scores except cough score showed a significant decrease in both groups (P0.05), but the tulobuterol group had significantly lower symptom scores than the salbutamol group (P0.05). On the fourteenth day of treatment, both groups had a significant decrease in cough score (P0.05), but the tulobuterol group had a significantly lower cough score than the salbutamol group (P0.05). One child developed hand trembling in the salbutamol group, while no adverse event occurred in the tulobuterol group.Compared with oral salbutamol sulfate, tulobuterol patch has a better therapeutic efficacy and a higher safety in children with mild or moderate acute asthmatic attack.