Systematic Infection of Chlamydia Pneumoniae.

BACKGROUND: Chlamydia pneumoniae (Cpn) is one of the most common respiratory pathogens in children and adults. It is characterized as an obligate intracellular parasite. Peripheral blood monocytes (PBMC), lymphocytes, and macrophages are involved in spreading chlamydia infection to extrapulmonary organs indicating that Cpn infection can cause systematic symptoms in vivo via blood transmission. METHODS: This review summarizes the mechanisms of Cpn infection in host cells, the immune response of the body, and the relationship between Cpn infection and some chronic diseases. RESULTS: Cpn participation in extrapulmonary chronic diseases has been proven owing to the presence of Cpn DNA in AS plaque, nerve tissues, and synovium tissues of the joints. CONCLUSIONS: Cpn infection is related to the development of chronic diseases such as atherosclerosis, Alzheimer's Disease (AD), and reactive arthritis through in vivo and in vitro experiments.

Prevalence and clinical characteristics of septicemia in children with Mycoplasma pneumoniae pneumonia.

BACKGROUND: Mycoplasma pneumoniae (MP) pneumonia in children can be challenging to treat, and the impact of MP blood infection is unclear. The present study aims to determine the prevalence and clinical characteristics of MP septicemia among pediatric patients. METHODS: Children hospitalized at our center for MP pneumonia between October 2017 and June 2018 were included. Healthy controls visiting our outpatient clinic for regular physical examinations were also enrolled. MP was detected by real-time polymerase chain reaction (qPCR) analysis of plasma and peripheral blood mononuclear cell (PBMC) samples. RESULTS: Sixty-one children with MP pneumonia and 30 healthy children were included. Among children with MP infection, 31 (50.8%) were positive for MP by qPCR (19 in plasma samples, 8 in PBMC samples, and 4 in both). All healthy controls were negative for MP by qPCR. CONCLUSIONS: The prevalence of MP septicemia in children with MP pneumonia is moderate. However, detection of MP in blood samples may have limited clinical value for guiding treatment.

Potential factors involved in the causation of rhabdomyolysis following status asthmaticus.

Rhabdomyolysis is a rare but potentially fatal complication of status asthmaticus. Since the first case was reported in 1978, only a few dozen cases have been described till date. We performed a literature review with the aim to characterize the pathophysiological basis of the occurrence of rhabdomyolysis in patients with status asthmaticus. Excessive exertion of respiratory muscles, hypoxia and acidosis, electrolyte imbalance, infections, some drugs used for asthma control, use of mechanical ventilation, prolonged cardiopulmonary resuscitation, higher age of the patient and some underlying diseases or genetic factors appear to be involved in its causation. In patients with status asthmaticus, it is important to pay more attention to these factors and to closely monitor creatine kinase levels in blood so as to ensure early detection of rhabdomyolysis.

Budesonide suspension nebulization treatment in Chinese pediatric patients with cough variant asthma: a multi-center observational study.

OBJECTIVE: To describe the impact of nebulized budesonide inhalation suspension (BIS) on guardian-reported symptoms in Chinese pediatric patients with cough variant asthma (CVA). METHODS: This was a secondary analysis of a prospective, non-interventional study conducted at 39 Chinese sites. Patients with CVA aged ≤5 years were classified according to the severity of baseline symptoms: mild (symptom score ≤3) or severe (symptom score >3). Daytime and night-time symptom scores, disease control, use of bronchodilators, and improvements in symptoms control were compared after 1, 3, 5 and 7 weeks of treatment between groups. RESULTS: Among 914 patients, 821 (89.8%) completed the 7-week treatment. Among all patients, 368 (40.3%) were classified as mild CVA and 529 (57.9%), as severe CVA. Symptom scores in the severe group were higher than those in the mild group at weeks 1, 3, and 5 (p < 0.05), but not at week 7 (p > 0.05). Further, more patients in the mild group achieved disease control at any time point (98.6% at 3 weeks and 99.7% at 7 weeks), compared with the patients in the severe group (p < 0.001). The proportion of patients requiring bronchodilators differed between the groups until week 5 (p < 0.001). No severe or drug-related adverse events were reported. CONCLUSIONS: Individualized BIS treatment should be formulated according to the severity of baseline symptoms in CVA patients. Patients with mild CVA showed improvement after a shorter treatment time, while patients with severe CVA might require a longer time to respond to the treatment.

[Effects of early cigarette smoke exposure on the functions of T-lymphocyte subsets in asthmatic mice].

OBJECTIVE: To explore the effects of early cigarette smoke exposure on the immune functions of T-lymphocyte subsets in asthmatic mice model. METHODS: Forty mice (20 days) were randomly allocated into four groups: air control group, cigarette smoke (CS) control group, air+ovalbumin (OVA) group, and CS+OVA group (n = 10 each). The CS control and CS+OVA groups were exposed to cigarette smoke for 3 weeks while the other two groups exposed to air. At an age of 8 weeks, air+OVA and CS+OVA groups had OVA sensitization for establishing an asthma model while the other two groups were selected as control. The percentage of regulatory T cells (Treg), effect of T cell (Te) subgroup including T helper type (Th)1, Th2 and Th17 in splenic mononuclear T cell were determined by flow cytometry. The levels of transforming growth factor-ß (TGF-ß), interleukin (IL)-4, IL-5, IL-10, IL-13, IL-17A and interferon-γ (IFN-γ) in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). And the percentage ratios of Treg to Te were compared among four groups. RESULTS: The percentages of Th1, Th2, Th17 and Treg in splenic mononuclear of CS+OVA group ((21.47 ± 2.84)%, (16.33 ± 3.02)%, (1.89 ± 0.23)% and (2.92 ± 0.40)%, respectively) were all significantly higher than those in air+OVA group ((14.78 ± 2.21)%, (9.72 ± 1.46)%, (1.01 ± 0.12)% and (1.84 ± 0.22)% , respectively), the levels of IL-4, IL-5, IL-10, IL-13, IL-17A, IFN- γ and TGF-ß in BALF of CS+OVA group ((138.6 ± 18.9), (195.3 ± 32.6), (22.8 ± 3.9), (716.9 ± 123.6), (62.8 ± 7.9), (173.2 ± 25.5) and (66.5 ± 8.2) ng/L, respectively) were all significantly higher than those in air+OVA group ((90.1 ± 13.7), (128.5 ± 21.8), (14.4 ± 2.9), (421.4 ± 60.4), (40.4 ± 6.2), (113.8 ± 16.9) and (42.9 ± 3.8) ng/L, respectively) (all P < 0.05). No significant difference of Treg/Te percentage ratio existed in mice spleen mononuclear cells between air+OVA group and CS+OVA group (P > 0.05). CONCLUSION: Early cigarette smoke exposure could significantly exacerbate T cell immune dysfunction in asthmatic mice.

Intestine-derived Clostridium leptum induces murine tolerogenic dendritic cells and regulatory T cells in vitro.

Patients with autoimmune and allergic diseases frequently present with reduced numbers and functionally impaired regulatory T cells (Tregs) and/or tolerogenic dendritic cells (tDCs). tDC-mediated regulation of Treg proliferation (numbers) and activation is crucial to establishing and maintaining an appropriate level of immune tolerance. Colonic colonization of Clostridium spp. is associated with accumulation of Tregs, which inhibits development of inflammatory lesions. To investigate whether infection with the Clostridium leptum sp. can specifically induce Tregs and/or tDCs bone marrow-derived dendritic cells were cultured in the presence or absence of C. leptum then co-cultured with CD4(+)CD25(-) T cells or not. Changes in tDC numbers, Treg numbers, percentages of T cell subsets, and expression of cytokines related to Tregs (IL-10 and transforming growth factor-beta (TGF-ß1)), DCs (IL-12p40 and IL-6) and effector T cells (IFN-γ, IL-4, IL-5, IL-13, and IL-17A) were measured. In the co-culture system, C. leptum-stimulated tDCs were able to increase the percentage and total number of Tregs attenuate activation of T helper cells (Th1, Th2, and Th17), and decrease the amount of secreted IL-4, IL-5, IL-13, IFN-γ and IL-17A. Thus, C. leptum exposure can induce the tDC-mediated stimulation of Tregs while disrupting the immune inflammatory response mediated by Th1, Th2 and Th17 cells.

Post-infectious bronchiolitis obliterans in children: a review of 42 cases.

BACKGROUND: This study aimed to describe the clinical characteristics, radiological features and outcomes of 42 children with post-infectious bronchiolitis obliterans (PIBO). METHODS: Forty-two children diagnosed with PIBO were prospectively studied at the First Hospital of Jilin University in northern China between January, 2008 and January, 2013. Their clinical characteristics, lung high resolution computed tomography (HRCT) findings and pulmonary function tests were reported. RESULTS: In children with PIBO, adenovirus was the most common etiologic agent (21/42), followed by Mycoplasma pneumoniae (M. pneumoniae). All of the patients presented with repeated wheezing and tachypnea. In addition, 22 patients required intensive management, while six patients required home oxygen therapy. HRCT findings were consistent with the PIBO diagnosis in all of the patients. Pulmonary function testing was useful in evaluating therapeutic responses. Systemic steroids combined with azithromycin were effective for PIBO treatment. CONCLUSIONS: Severe adenovirus bronchiolitis and M. pneumoniae infections have a higher risk of development for PIBO. HRCT and pulmonary function testing are useful in the diagnosis of PIBO. The degree of airway obstruction did not differ significantly between adenovirus and M. pneumoniae. A combination of steroids and azithromycin offers some benefit in treating these patients.

Allium sativum-derived allitridin inhibits Treg amplification in cytomegalovirus infection.

This study investigated the effects of allitridin compound on murine cytomegalovirus (MCMV)-induced regulatory T cell (Treg; CD4(+) CD25(+) Foxp3(+) ) amplification in vivo and in vitro. One hundred twenty MCMV-infected mice were allocated at random into two groups for treatment with allitridin or placebo. Another 120 mock-infected mice were randomly allocated as controls for the allitridin treatment and placebo treatment groups. The mice were euthanized at various time points after infection (out to 120 days) to evaluate the effects of treatment on Treg presence and function, as well as MCMV infective load. Co-culture with mouse embryo fibroblasts (MEF) and MCMV was performed to evaluate allitridin-mediated Treg and anti-CMV effects. The maximum tolerance concentration (MTC) of allitridin was used to treat cells for 3 days. Changes in Foxp3 mRNA and protein levels, percentages of T cell subsets, and Treg-related cytokines (IL-10 and TGF-ß) were measured. Allitridin treatment did not influence Foxp3 expression and Treg proportion in uninfected mice, but did down-regulate each in infected mice during the chronic infection period. Additionally, allitridin treatment reduced the MCMV load in salivary glands. MTC allitridin treatment of co-cultures partially blocked MCMV induction of Foxp3 mRNA and protein expression. In vitro treatment with allitridin also increased significantly the percentages of Tc1, Tc2, and Th1, reduced the secreted levels of IL-10 and TGF-ß1, and significantly suppressed viral loads. In conclusion, allitridin can promote MCMV-induced Treg expansion and Treg-mediated anti-MCMV immunosuppression. Therefore, allitridin may be useful as a therapeutic agent to enhance the specific cellular immune responses against CMV.

Status of asthma control in children and the effect of parents' knowledge, attitude, and practice (KAP) in China: a multicenter study.

BACKGROUND: Asthma is the most common chronic respiratory disease seriously endangering the health of children. But disease awareness and self-management skills are relatively poor in children; parents play an important role in the control of childhood asthma. OBJECTIVE: To investigate the status of asthma control and severity of asthma in children and to identify impact factors. METHODS: We studied 1 tertiary hospital in each of the 29 provinces. A total of 2,960 parents with children with asthma who visited those hospitals were selected for the knowledge, attitude, and practice (KAP) questionnaire survey, and separated into the controlled asthma group and uncontrolled asthma group according to children's asthma conditions in the past 12 months. Multivariate analysis was carried out based on the answers to 28 tested factors. RESULTS: In the past 12 months, 66.0% of children with asthma had asthma attacks, 26.8% visited an emergency room, and 16.2% were hospitalized. The total cost for asthma was significantly higher in the uncontrolled group than controlled group (χ(2) = 23.14, P < .01). Twelve protective factors of asthma control were founded, such as older age of children, long disease course, high KAP scores of parents, compliance with using nasal steroids, and knowledge of "3 or more times recurrent wheezing suggesting asthma." The risk factors were eczema and family history of asthma. CONCLUSION: Children's asthma is poorly controlled. The cost of asthma is significantly higher in uncontrolled asthma than in controlled. The age of children, course of asthma, personal history of allergy, family history of asthma, parents' education level, and parents' KAP are factors that affect asthma control.

Effect of oral feeding with Clostridium leptum on regulatory T-cell responses and allergic airway inflammation in mice.

BACKGROUND: Allergic lung inflammation is mediated by allergen-specific T responses, which are negatively regulated by regulatory T cells (Tregs). Previous studies have reported that inoculation of indigenous Clostridium species in the early lives of mice can induce Tregs that colonize the colon. However, whether inoculation of C leptum alone in adult mice could induce systemic Treg responses and inhibit allergic airway inflammation remains unclear. OBJECTIVE: To investigate the effect of oral administration of C leptum on systemic Treg responses and allergic airway inflammation in a mouse model of asthma. METHODS: Adult BABL/c mice were injected with ovalbumin to induce asthma and treated orally with C leptum or vehicle daily for 2 weeks. The numbers of Foxp3(+)CD4(+)CD25(+) Tregs in both the spleen and mediastinal lymph nodes were examined by flow cytometry. After allergen challenge, the airway hyperresponsiveness of individual mice was measured, and the numbers of inflammatory infiltrates and the levels of cytokines in bronchoalveolar lavage fluids ere determined. RESULTS: Oral feeding with C leptum increased the percentage and total number of Tregs in the spleens and mediastinal lymph nodes at 14 days after inoculation and attenuated allergen-induced airway hyperresponsiveness and inflammation by inhibiting inflammatory cytokine production but enhancing interleukin 10 and transforming growth factor ß1 production in the lungs. CONCLUSION: Oral treatment with C leptum can attenuate induced allergic airway inflammation in adult mice.

[Levels of TNF-α, IL-6 and IL-10 in bronchoalveolar lavage fluid in children with Mycoplasma pneumoniae pneumonia].

OBJECTIVE: To study the levels and roles of cytokines TNF-α, IL-6 and IL-10 in bronchoalveolar lavage fluid (BALF) in children with Mycoplasma pneumoniae pneumonia (MPP). METHODS: The levels of TNF-α, IL-6 and IL-10 in BALF were measured using ELISA in children with MPP at acute stage (n=45) and at remission stage (n=30). Twenty children without lung lesions severed as the control group. RESULTS: The TNF-α, IL-6 and IL-10 levels in BALF were higher in children with MPP at acute stage than those in the control group (P<0.05). The levels of TNF-α and IL-6 in BALF at remission stage were reduced to the levels similar to the control group and were significantly lower than those at the acute stage in children with MPP. However, the levels of IL-10 in BALF remained at higher levels at remission stage in children with MPP. CONCLUSIONS: The levels of TNF-α, IL-6 and IL-10 in BALF increase in children with MPP at acute stage, suggesting that the cytokines may be involved in the pathogenesis of MPP.

Silencing IL-23 expression by a small hairpin RNA protects against asthma in mice.

To determine the impact of IL-23 knockdown by RNA interference on the development and severity of ovalbumin (OVA)-induced asthmatic inflammation, and the potential mechanisms in mice, the IL-23-specific RNAi-expressing pSRZsi-IL-23p19 plasmid was constructed and inhaled into OVA-sensitized mice before each challenge, as compared with that of control mice treated with alum or budesonide. Inhalation of the pSRZsi-IL-23p19, significantly reduced the levels of OVA-challenge induced IL-23 in the lung tissues by nearly 75%, determined by RT-PCR. In addition, knockdown of IL-23 expression dramatically reduced the numbers of eosinophils and neutrophils in BALF and mitigated inflammation in the lungs of asthmatic mice. Furthermore, knockdown of IL-23 expression significantly decreased the levels of serum IgE, IL-23, IL-17, and IL-4, but not IFNgamma, and its anti-inflammatory effects were similar to or better than that of treatment with budesonide in asthmatic mice. Our data support the notion that IL-23 and associated Th17 responses contribute to the pathogenic process of bronchial asthma. Knockdown of IL-23 by RNAi effectively inhibits asthmatic inflammation, which is associated with mitigating the production of IL-17 and IL-4 in asthmatic mice.

[Regulatory effects of inhaled steroids on expression of matrix metalloproteinase-9 and its inhibitor in asthmatic rats].

OBJECTIVE: To investigate the role of matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor (TIMP-1) in the pathogenesis of bronchial asthma and assess the effect of steroid treatment on MMP-9 and TIMP-1 levels. Matrix metalloproteinases are a family of zinc and calcium-dependent endopeptidases. Many MMPs such as MMP-1, MMP-2, MMP-3 are associated with asthma, in which MMP-9 is the key factor in asthma. Tissue inhibitor-1 of metalloproteinases is a specific inhibitor of MMP-9; the MMP-9 and TIMP-1 imbalance could lead to airway inflammation and remodeling in lung disease such as asthma. METHODS: Forty Wistar rats were divided into 4 groups randomly: control, asthma model 7 days (7-day group), asthma model 21 days (21-day group) and steroid treatment groups. Asthma model of rats were established by ovalbumin (OVA) sensitization and challenge with mist inhalation. The expression of MMP-9 and TIMP-1 in lung tissues was detected by immunocytochemistry, RT-PCR and Western blotting. RESULTS: (1) By observing the changes of action, tracing respiratory curves, detecting level of serum IgE level and observing the lung tissues sections, the authors demonstrated that the rat asthmatic models were successfully established. (2) The lung tissue sections of the asthma groups stained with hematoxiline and eosin (HE) showed many inflammatory cell infiltrations around the bronchioli and accompanying arterioles, hyperplasia of caliciform cells, broken bronchial mucous membrane and thickening of submucosal layer. The hyperplasia of airway smooth muscle and basement membrane were more significant in asthma model 21-day group than that in 7-day group. These changes were improved after treatment. (3) The expression of MMP-9 in rat's lung tissues: the expression was 2.71 +/- 0.37 in 7-day group, 1.76 +/- 0.27 in 21-day group, 0.88 +/- 0.18 in the treatment group and 0.52 +/- 0.10 in the control group (F = 151.52, P < 0.01). The expression of TIMP-1 in rat's lung tissues was 1.13 +/- 0.19 in the 7-day group, 1.55 +/- 0.24 in 21-day group, 0.77 +/- 0.15 in the treatment group and 0.47 +/- 0.08 in the control group (F = 69.46, P < 0.01). (4) The results of immunocytochemistry and protein expression were consistent with those of RT-PCR. CONCLUSION: The protein and mRNA expression level of MMP-9 and TIMP-1 was high in asthmatic rat's lung tissues. Down-regulation of the expression of MMP-9 and TIMP-1 by steroids may be one of the mechanisms by which airway inflammation and remodeling are inhibited in asthma.