OBJECTIVETo investigate the effect of heat shock factor 1 (HSF1) on airway hyperresponsiveness and airway inflammation in mice with asthma and possible mechanisms.

METHODSA total of 36 mice were randomly divided into four groups: control, asthma, HSF1 small interfering RNA negative control (siHSF1-NC), and siHSF1 intervention (n=9 each). Ovalbumin (OVA) sensitization and challenge were performed to induce asthma in the latter three groups. The mice in the siHSF1-NC and siHSF1 groups were treated with siHSF1-NC and siHSF1, respectively. A spirometer was used to measure airway responsiveness at 24 hours after the last challenge. The direct count method was used to calculate the number of eosinophils. ELISA was used to measure the serum level of OVA-specific IgE and levels of interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), and interferon-γ (IFN-γ) in lung tissues and bronchoalveolar lavage fluid (BALF). Quantitative real-time PCR was used to measure the mRNA expression of HSF1 in asthmatic mice. Western blot was used to measure the protein expression of HSF1, high-mobility group box 1 (HMGB1), and phosphorylated c-Jun N-terminal kinase (p-JNK).

RESULTSThe asthma group had significant increases in the mRNA and protein expression of HSF1 compared with the control group (P<0.05). The siHSF1 group had significantly reduced mRNA and protein expression of HSF1 compared with the siHSF1-NC group (P<0.05). The knockdown of HSF1 increased airway wall thickness, airway hyperresponsiveness, OVA-specific IgE content, and the number of eosinophils (P<0.05). Compared with the siHSF1-NC group, the siHSF1 group had significantly increased levels of IL-4, IL-5, and IL-13 and significantly reduced expression of IFN-γ in lung tissues and BALF (P<0.05), as well as significantly increased expression of HMGB1 and p-JNK (P<0.05).

CONCLUSIONSKnockdown of HSF1 aggravates airway hyperresponsiveness and airway inflammation in asthmatic mice, and its possible mechanism may involve the negative regulation of HMGB1 and JNK.

Animals ; Asthma ; etiology ; Bronchial Hyperreactivity ; etiology ; immunology ; Cytokines ; biosynthesis ; DNA-Binding Proteins ; analysis ; physiology ; Eosinophils ; physiology ; Female ; HMGB1 Protein ; analysis ; Heat Shock Transcription Factors ; Immunoglobulin E ; blood ; Mice ; Mice, Inbred BALB C ; Transcription Factors ; analysis ; physiology

OBJECTIVETo examine fractional exhaled nitric oxide (FeNO) values in 1-3-year-old children with asthma and analyze the correlation of FeNO with peripheral blood eosinophils (EOS) and lung function in these children.

METHODSA total of 111 children aged 1-3 years with asthma were enrolled. The children were classified into acute exacerbation (n=62) and remission groups (n=49) according to their symptoms. FeNO values, lung function, and peripheral blood EOS count were measured in these children. Sixty age-matched healthy children were enrolled as the control group.

RESULTSFeNO values were significantly higher in the acute exacerbation group (24.4 ppb) than in the remission group (18.0 ppb) and the control group (13.7 ppb) (P<0.05). The FeNO values in the remission group were significantly higher than in the control group (P<0.05). FeNO values were not significantly correlated with peripheral blood EOS count and lung function parameters (PEF, TEF25, TEF50, and TEF75).

CONCLUSIONSMeasurement of FeNO is useful to evaluate the disease activity in children with asthma aged 1 to 3 years, but the FeNO values are not correlated with peripheral blood EOS count and lung function.

Asthma ; blood ; physiopathology ; Breath Tests ; Child, Preschool ; Eosinophils ; physiology ; Female ; Humans ; Infant ; Lung ; physiopathology ; Male ; Nitric Oxide ; metabolism

OBJECTIVETo examine the levels of nerve growth factor (NGF) and interleukin-4 (IL-4) in the induced sputum of children with cough variant asthma (CVA), with the aim of studying the roles of NGF and IL-4 in childhood CVA.

METHODSThirty-four children with CVA were enrolled in this study. Twenty healthy children were used as a normal control group. The induced sputum was separated into supernatant and cells. Hematoxylin and eosin staining was used to count differential cells. The expression of NGF and IL-4 in supernatant was measured using ELISA. The mRNA expression of NGF and IL-4 in cells was determined by Real-time PCR analysis.

RESULTSThe percentage of eosinophils in the CVA group was significantly higher than in the control group [(13.4±3.6)% vs (2.6±1.7)%; P<0.01]. The expression of NGF and IL-4 protein and mRNA in induced sputum was significantly higher in the CVA group than in the control group (P<0.05). The expression of NGF and IL-4 protein and mRNA was positively correlated with the percentage of eosinophils (P<0.01). The expression of NGF and IL-4 protein and mRNA in induced sputum was significantly reduced in the CVA group after treatment (P<0.05).

CONCLUSIONSEosinophils infiltration and increased expression of NGF and IL-4 play key roles in the development of childhood CVA, suggesting that they may be useful in the diagnosis and treatment of childhood CVA.

Asthma ; complications ; metabolism ; Child ; Child, Preschool ; Cough ; etiology ; Eosinophils ; physiology ; Female ; Humans ; Interleukin-4 ; analysis ; genetics ; physiology ; Male ; Nerve Growth Factor ; analysis ; genetics ; physiology ; Sputum ; metabolism

OBJECTIVETo study the efficacy and safety of specific sublingual immunotherapy with dermatophagoides farinae drops in the treatment of cough variant asthma in children.

METHODSA total of 106 children aged 4-14 years old with cough variant asthma and positive skin prick test responses to dermatophagoides farinae allergens were randomly divided into two groups: SLIT group (n=53), which received specific sublingual immunotherapy with dermatophagoides farinae drops as well as standardized treatment and conventional treatment group (n=53), which received standardized treatment alone. Improvement in cough/asthma symptom scores and the time taken for symptoms to improve were observed after treatment. Serum eosinophil (EOS) level and peak expiratory flow (PEF) were measured after treatment. The side effects were observed.

RESULTSCompared with the conventional treatment group, the SLIT group showed significant decrease in symptom scores and serum EOS level and significant increase in PEF (P<0.05). The time at which symptoms began to improve in the SLIT group was earlier than in the conventional treatment group (P<0.05). The effective rate in the SLIT group was significantly higher than in the conventional treatment group (85% vs 68%; P<0.05). Local reactions such as redness, swelling, and itching occurred in some children of the SLIT group but disappeared on the following day.

CONCLUSIONSSpecific sublingual immunotherapy with dermatophagoides farinae drops is an effective and highly safe treatment for cough variant asthma in children.

Administration, Sublingual ; Adolescent ; Antigens, Dermatophagoides ; immunology ; Asthma ; therapy ; Child ; Child, Preschool ; Cough ; therapy ; Desensitization, Immunologic ; adverse effects ; Eosinophils ; physiology ; Female ; Humans ; Male

OBJECTIVEIt is known that Siglec-8 is selectively expressed on human eosinophils at a high level and mediates eosinophil apoptosis when crosslinked with its antibody. The aim of our review is to elucidate the molecular and biological characteristic of Siglec-8 and then discuss the function and possible mechanisms of Siglec-8 in eosinophils. Thereby, we will expand our understanding to the regulation of eosinophil apoptosis, and provide important clues to the treatment of asthma and other hyper-eosinophilic diseases.

DATA SOURCESMost articles were identified by searching of PubMed online resources using the key term Siglecs.

STUDY SELECTIONMainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected.

RESULTSSiglec-8 is selectively expressed on human eosinophil and can specifically induce eosinophil apoptosis.

CONCLUSIONThe restricted expression of Siglec-8 on human eosinophil and the rapid progress in understanding its role as cell signaling and activation of death receptors have made it an attractive target for treatment of asthma and other hyper-eosinophilic diseases.

Apoptosis ; genetics ; physiology ; Asthma ; metabolism ; therapy ; Eosinophils ; cytology ; metabolism ; Humans ; Sialic Acid Binding Immunoglobulin-like Lectins ; metabolism

OBJECTIVEAndrographolide, the active component in andrographis paniculata, has potent anti-inflammatory actions. This study aimed to evaluate the effects of andrographolide on eosinophil granulocytes (EOS) and the expression of eotaxin and IL-5 in mice with asthma.

METHODSBALB/c mice were randomly assigned into normal control, asthma, budesonide treatment and andrographolide treatment groups (n=8 each). Mice in the latter three groups were sensitized and challenged with ovalbumin (OVA) to induce asthma. ELISA was used to detect the concentrations of eotaxin and IL-5 in bronchoalveolar lavage fluid (BALF) and peripheral blood. The expression of eotaxin mRNA and IL-5 mRNA in lung tissues was detected by real-time quantitative PCR.

RESULTSAndrographolide treatment significantly decreased EOS count in BALF (P<0.05) and the effect of andrographolide was better than the effect of budesonide. Andrographolide treatment significantly down-regulated the expression of eotaxin and IL-5 in BALF, lung eotaxin mRNA expression and blood IL-5 expression (P<0.05), but the effects of andrographolide were poorer than the effects of budesonide. Andrographolide treatment resulted in a decrease in blood eotaxin expression and lung IL-5 mRNA expression and the effects of andrographolide were similar to budesonide.

CONCLUSIONSAndrographolide can down-regulate the expression of IL-5 and eotaxin and thus suppress the inflitration of EOS in a mouse model of asthma.

Animals ; Asthma ; drug therapy ; Bronchoalveolar Lavage Fluid ; cytology ; Chemokine CCL11 ; analysis ; genetics ; Diterpenes ; pharmacology ; Eosinophils ; drug effects ; physiology ; Female ; Interleukin-5 ; analysis ; genetics ; Mice ; Mice, Inbred BALB C ; RNA, Messenger ; analysis

BACKGROUNDThe airway inflammation could be assessed by some noninvasive approaches. To investigate the value of eosinophil counts in induced sputum and fractional concentration of exhaled nitric oxide (FENO) for the regimen adjustment in patients with asthma, the correlation was analyzed between the two parameters and lung function parameter (forced expiratory volume in one second (FEV(1))).

METHODSSixty-five outpatients with mild to moderate non-exacerbation asthma from Beijing Chao-Yang Hospital were enrolled as treatment group. Combined medications of inhaled corticosteroids plus long-acting beta-2 agonist were administered for one year. Lung function parameters, eosinophil counts in induced sputum, concentration of exhaled nitric oxide and the Asthma Control Test scores were recorded, at regular intervals in the follow-up period. Twenty-one healthy volunteers were enrolled as control group and underwent examination of eosinophil counts in induced sputum, lung function and concentration of exhaled nitric oxide.

RESULTSSixty-three subjects from treatment group completed follow-up period for one year or longer. Mean FEV(1) value of the 63 subjects was (2.75 ± 0.54) L at baseline, (2.97 ± 0.56) L and (3.07 ± 0.52) L at month 3 and month 6, respectively, and maintained as (3.14 ± 0.51) L in the following six months. Mean FENO decreased from (61 ± 25) parts per billion (ppb) at baseline to (32 ± 19) ppb at month 3 (P < 0.05), and continued to decrease to (22 ± 12) ppb at month 6, the difference being significant when compared to both baseline and control group ((13 ± 8) ppb). Mean eosinophil counts decreased to (0.032 ± 0.011) × 10(6)/ml at month 3, which was significantly different from baseline ((0.093 ± 0.023)×10(6)/ml) and the control group ((0.005 ± 0.003)×10(6)/ml (both P < 0.05). The eosinophil counts in induced sputum correlated positively with concentration of FENO in the first six months (all P < 0.05). The concentration of FENO had a significant negative correlation with FEV(1) value (all P < 0.05) in any time point in the follow-up period. The Asthma Control Test scores were 18 ± 5, 19 ± 7, 23 ± 2, 24 ± 1 and 24 ± 1 at months 1, 3, 6, 9 and 12, respectively, which were significantly different from the score at baseline (14 ± 3) (P < 0.05). The most rapid clinical effect was observed at the second month after treatment.

CONCLUSIONEosinophil counts in induced sputum and FENO are sensitive parameters to detect airway inflammation and may be useful in evaluating the efficacy of treatment and adjusting medication regimens.

Adult ; Asthma ; immunology ; physiopathology ; Breath Tests ; Eosinophils ; physiology ; Female ; Humans ; Leukocyte Count ; Lung ; physiopathology ; Male ; Middle Aged ; Nitric Oxide ; analysis ; Sputum ; cytology

Prostaglandin D2 (PGD2) is a major prostanoid, produced mainly by mast cells, in allergic diseases, including bronchial asthma. PGD2-induced vasodilatation and increased permeability are well-known classical effects that may be involved in allergic inflammation. Recently, novel functions of PGD2 have been identified. To date, D prostanoid receptor (DP) and chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2) have been shown to be major PGD2-related receptors. These two receptors have pivotal roles mediating allergic diseases by regulating the functions of various cell types, such as TH2 cells, eosinophils, basophils, mast cells, dendritic cells, and epithelial cells. This review will focus on the current understanding of the roles of PGD2 and its metabolites in TH2 inflammation and the pathogenesis of bronchial asthma.
Asthma/*etiology/immunology ; Basophils/physiology ; Eosinophils/physiology ; Humans ; Mast Cells/physiology ; Prostaglandin D2/*physiology ; Receptors, Immunologic/physiology ; Receptors, Prostaglandin/physiology ; Th2 Cells/*immunology

OBJECTIVETo study the value of eosinophils (EOS) and interleukin-17 (IL-17) in nasopharyngeal secretions in the evaluation of progress of wheezing in children under 5 years old.

METHODSFifty-three children under five years old who had recurrent wheezing were classified into two groups: wheezing group I with atopic body (n=27) and wheezing group II without atopic body (n=26). Twenty pre-surgical children with non-infectious disease were used as the control group. Nasopharyngeal secretions were collected. Inflammatory cells in nasopharyngeal secretions were counted under the microscope. IL-17 levels in supernatants were measured using ELISA.

RESULTSEOS counts in nasopharyngeal secretions in wheezing group I were significantly higher than those in wheezing group II and the control group (p<0.05, p<0.01, respectively). There were no significant differences in EOS counts between wheezing II and the control groups. The IL-17 levels in both wheezing groups were significantly higher than those in the control group (p<0.01), and the wheezing group I had increased IL-17 levels than wheezing group II (1 474+/-974 pg/mL vs 788+/-132 pg/mL; p<0.05). The IL-17 level was positively correlated with the EOS counts in wheezing group I (r=0.62, p<0.05).

CONCLUSIONSEOS counts and IL-17 levels in nasopharyngeal secretions may be used as indices for identifying the tendency to develop asthma in children under 5 years old with wheezing.

Child, Preschool ; Eosinophils ; physiology ; Female ; Humans ; Infant ; Interleukin-17 ; analysis ; Leukocyte Count ; Male ; Nasopharynx ; secretion ; Respiratory Sounds ; immunology

OBJECTIVETo study the role of cell adhesion molecule CD44 in the lung on airway inflammatory response in rats with asthma.

METHODSThirty-two Sprague-Dawley rats were randomly divided into normal control and asthma groups. Asthma was induced by repeated inhalation of ovalbulium. CD44 expression in the lung was detected by semi-quantitatively reverse transcription-polymerase chain reaction (RT-PCR) and immuno-histochemical staining 1 week and 2 weeks after ovalbulium challenge. Differential leukocytes (mononuclear phagocytes, neutrophils, eosinophils, and lymphocytes) in bronchoalveolar lavage fluid (BALF) were counted.

RESULTSCD44 expression in the lung increased 1 week after ovalbulium challenge (<0.05) and increased more significantly 2 weeks after ovalbulium challenge (<0.01) compared with that in the control group. The percentages of lymphocytes and eosinophils in BALF increased, while the percentage of BALF mononuclear phagocytes decreased significantly 1 week and 2 weeks after ovalbulium challenge in the asthma group compared with those in the control group (<0.05). An increased percentage of neutrophils was found 1 week after ovalbulium challenge in the asthma group compared with the control group (<0.05). CD44 expression in the lung was positively correlated with the percentages of lymphocytes and eosinophils in BALF in the asthma group 1 week and 2 weeks after ovalbulium challenge, in contrast, lung CD44 expression was negatively correlated with the percentage of mononuclear phagocytes in the asthma group 1 week after ovalbulium challenge.

CONCLUSIONSCD44 was over-expressed in the lung and closely related to inflammatory infiltration in rats with asthma. CD44 may play an important role in the development of airway inflammatory in asthma.

Animals ; Asthma ; immunology ; Bronchoalveolar Lavage Fluid ; cytology ; Eosinophils ; physiology ; Hyaluronan Receptors ; analysis ; genetics ; physiology ; Inflammation ; etiology ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley