Dietary micronutrients/antioxidants and their relationship with bronchial asthma severity

BACKGROUND: Because little is known about micronutrient/antioxidant intake and asthma severity, we investigated dietary intake and plasma/serum levels of micronutrients/antioxidants in a group of asthma patients with various degrees of severity, and compared the results with healthy subjects. METHODS: A case control study was carried out on 118 asthma patients and 121 healthy subjects. The severity of the disease was classified by division of patients into four groups. Normal dietary micronutrient/antioxidant intake was estimated from a food frequency questionnaire. Plasma/serum levels of vitamins C, E, and A, selenium, magnesium, zinc, and platelet glutathione peroxidase (GSH-Px) activity were also determined. RESULTS: No differences in daily micronutrient/antioxidant intake were seen between patients and healthy subjects. The severity of the disease showed no significant relationship with micronutrient/antioxidant intake. There were no differences in plasma/serum levels in any of the micronutrients/antioxidants between healthy subjects and asthmatics. Nor were any differences found between asthma groups in severity in the biochemical measures, except in platelet GSH-Px activity, which was significantly lower in the most severe groups. CONCLUSIONS: In this study, we found no evidence of any association between micronutrient/antioxidant intake or plasma/serum levels of micronutrients/antioxidants and asthma. Reduction of platelet GSH-Px activity in the most severe patients suggests that these patients have a diminished capacity to restore part of the antioxidant defences.     

Airway inflammation in asthma and perennial allergic rhinitis. Relationship with nonspecific bronchial responsiveness and maximal airway narrowing

BACKGROUND: Eosinophilic airway inflammation is the hallmark of asthma, but it has also been reported in other conditions such as allergic rhinitis. We have tested whether the analysis of cells and chemicals in sputum can distinguish between patients with mild allergic asthma, those with allergic rhinitis, and healthy controls. The relationship between inflammation markers in sputum and nonspecific bronchial hyperresponsiveness to methacholine (BHR) (PD20 and maximal response plateau [MRP] values) was also evaluated. METHODS: We selected 31 mild asthmatics and 15 rhinitis patients sensitized to house-dust mite. As a control group, we studied 10 healthy subjects. Every subject underwent the methacholine bronchial provocation test (M-BPT) and sputum induction. Blood eosinophils and serum ECP levels were measured. Sputum cell differentials were assessed, and eosinophil cationic protein (ECP), tryptase, albumin, and interleukin (IL)-5 levels were measured in the entire sputum supernatant. RESULTS: Blood eosinophils and serum ECP levels were higher in asthma patients and rhinitis than in healthy controls, but no difference between asthma patients and rhinitis patients was found. Asthmatics had higher eosinophil counts and higher ECP and tryptase levels in sputum than rhinitis patients or control subjects. Sputum albumin levels were higher in asthmatics than in controls. Rhinitis patients exhibited higher sputum eosinophils than healthy controls. An association between sputum eosinophil numbers and MPR values (r= -0.57) was detected, and a trend toward correlation between sputum ECP levels and PD20 values (r= -0.47) was found in the rhinitis group, but not in asthmatics. No correlation between blood eosinophilic inflammation and lung functional indices was found. CONCLUSIONS: Induced sputum is an accurate method to study bronchial inflammation, allowing one to distinguish between rhinitis patients and mildly asthmatic patients. The fact that no relationship was detected between sputum inflammation and BHR suggests that other factors, such as airway remodeling, may be at least partly responsible for BHR in asthma.     

Macrophage migration inhibitory factor (MIF) in bronchial asthma

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine favouring the secretion of TNFalpha and IL-8 and counteracts anti-inflammatory effects of corticosteroids. Airways inflammation is a central feature of bronchial asthma and is characterized by the accumulation of eosinophils. OBJECTIVE: The aim of this study was to investigate whether MIF is related to asthma symptoms and eosinophil accumulation in the airways. METHODS: Serum MIF levels were measured by an enzyme-linked immunosorbent assay in 44 healthy subjects and 44 asthmatics. Levels of MIF in induced sputum were measured in 10 healthy subjects and 15 asthmatics. Levels of eosinophil cationic protein (ECP) in induced sputum were measured by a radioimmunosorbent assay. Fluorescence double immunostaining was conducted to examine cellular source and localization of MIF. RESULTS: Serum MIF levels were significantly increased in asthmatic patients compared with age and sex-matched control subjects. Symptomatic patients had a higher MIF level than asymptomatic patients. Induced sputum obtained from asthmatics contained higher levels of MIF than those from control subjects. MIF levels in induced sputum were correlated with ECP levels in induced sputum. MIF was colocalized with eosinophil peroxidase staining in the cytoplasm of sputum cells. CONCLUSION: Increased MIF levels are associated with asthma symptoms and one of the cellular sources of MIF in the airways are eosinophils.     

Eotaxin in induced sputum of asthmatics: relationship with eosinophils and eosinophil cationic protein in sputum

BACKGROUND: Eosinophilic inflammation is a crucial aspect of allergic diseases such as bronchial asthma. An eosinophil-active chemokine, eotaxin, may play a role in the pathogenesis of the tissue eosinophilia accompanying asthma. METHODS: Induced sputa were obtained from 53 patients with atopic asthma and six healthy subjects, and the concentration of eotaxin in the sputum was measured by ELISA. We investigated whether the sputum content of eotaxin is related to 1) asthma status or corticosteroid therapy, and 2) other sputum indices, including percentage of eosinophils and concentration of eosinophil cationic protein (ECP). RESULTS: The patients with stable or unstable asthma showed significantly higher concentrations of sputum eotaxin than the normal controls. The level of sputum eotaxin demonstrated a positive correlation with the percentage of eosinophils in stable asthmatics not receiving corticosteroid therapy, but not in stable patients treated with corticosteroids, or in unstable patients. Sputum eotaxin demonstrated a positive correlation with ECP in asthmatic patients who were either in a stable state or not receiving steroid therapy. CONCLUSIONS: The elevated level of eotaxin detected in association with increased eosinophils and ECP in the sputum of asthmatics suggests that eotaxin is involved in the pathogenesis of eosinophilic airway inflammation. The relationship of eotaxin to airway eosinophilia may be modified by the stability status of asthma and corticosteroid therapy.     

The effect of disodium cromoglycate (DSCG) on the levels of albumin and the immunoglobulins IgA, IgG, IgM and IgE in sputum

Sputum samples from control subjects with cardiac disease and from patients with asthma were assayed for albumin content and immunoglobulins IgA, IgG, IgM and IgE. The asthmatics were divided into three groups: one group had received disodium cromoglycate (DSCG) for at least 48 hr prior to sampling, another group was sampled daily after commencing DSCG therapy and the third group were not taking DSCG. Albumin and immunoglobulins accounted for approximately 8% of the total sputum proteins in each of the four groups of subjects. There was no significant difference in the mean sputum levels of albumin or the immunoglobulins, when expressed as a percentage of total sputum proteins, between the subjects in each group. However, the ratios of IgA/albumin and IgA/IgG in the asthmatic group receiving DSCG were significantly lower than the corresponding ratios in sputa from both asthmatics and control subjects with cardiac disease. The sputum IgE levels tended to be higher in the asthmatics than in the control group, but DSCG therapy had little effect upon sputum IgE levels.     

VEGF levels in asthmatic airways do not correlate with plasma extravasation

BACKGROUND: Vascular permeability/vascular endothelial growth factor (VEGF) is a multifunctional cytokine which plays a role in chronic inflammation and angiogenesis. Its expression in bronchoalveolar lavage (BAL) has not been determined although VEGF may be relevant to the pathophysiology of asthma in which oedema is an important feature. METHODS: We studied VEGF, albumin and IgA immunoreactive levels in the BAL fluids obtained from 27 chronic stable asthmatics, nine untreated chronic bronchitis patients and 15 control subjects. RESULTS: BAL fluid levels of VEGF and VEGF normalized to IgA were not significantly different in any patient group. Both asthmatic steroid- and non-steroid-treated groups had significantly lower albumin levels in their BAL fluids explaining most of the 179% increased VEGF normalized to albumin ratios in non-steroid treated asthmatics. Moreover, VEGF and albumin markers correlated in control subjects (r = 0.73, P = 0.006) and in chronic bronchitics (r = 0.75, P = 0.03, Spearman test), but not in asthmatics. VEGF was inversely correlated with asthma severity (GINA/NHLBI scores) in non-steroid treated asthmatics (tau = - 0.52, P = 0.009, Kendall test). CONCLUSIONS: Thus, the potential role of VEGF in asthma requires further studies on bronchial biopsies and induced sputum.     

Increased release of matrix metalloproteinase-9 in the plasma of acute severe asthmatic patients.

BACKGROUND: Matrix metalloproteinases (MMPs) are likely to be relevant mediators of the extracellular matrix (ECM) degradation and airway remodelling. OBJECTIVE: We have compared the levels of MMPs, eotaxin and soluble interleukin 2 receptor (IL-2R) in the plasma of healthy subjects, atopic patients and asthmatic patients. METHODS: The asthmatic patients were separated into two groups, either well controlled on inhaled therapy or acute severe asthma. Patients with acute severe disease had all received systemic corticosteroids from 12 to 48 h before the blood was taken. Blood was recovered in EDTA tubes, incubated with either f MLP, PMA or vehicle for 10 min and centrifuged. MMP-9, TIMP-1, IL-2R and eotaxin levels were measured in the plasma by ELISA. Moreover, the activity of MMPs was also evaluated by zymography. RESULTS: An increased basal level of MMP-9 and IL2-R was observed in acute severe asthma. Following stimulation with f MLP and PMA there was an enhanced production of MMP-9 in the plasma of all groups of patients. However, the MMP-9 level was significantly enhanced in acute severe asthma, compared with the others. No difference was found for the TIMP-1 level between the patients. The eotaxin level in plasma was found to be significantly lower in acute severe asthmatics compared with the others groups. Zymography technique showed a significant increased activity of MMP-9 (92 kDa) but not MMP-2 (66 kDa) in the plasma of patients with acute asthma. CONCLUSION: The increased in MMP-9 production and activity observed in the present study suggests a process of extracellular matrix degradation in acute severe asthmatic patients and proposes MMP-9 as a non-invasive systemic marker of inflammation and airway remodelling in asthma.     

The influence of inhalative corticosteroids on circulating Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Neurotrophin-3 in allergic asthmatics

BACKGROUND: The neurotrophins Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin (NT)-3 are produced, stored and released by various immunological cells. The influence of NTs upon the function of these cells is described. Elevated plasma levels were found in inflammatory, autoimmune and allergic diseases with the highest levels in allergic asthma. A connection between bronchial hyper-responsiveness and serum levels has been reported. OBJECTIVE: Little is known about the influence of treatment with inhaled corticosteroids (ICS) on serum NT levels and their influence on the asthmatic state. METHODS: Eighty-seven volunteers were studied. Thirty-eight were stable allergic asthmatics with constant ICS doses, 29 were asthmatics not receiving anti-asthmatic treatment and 20 were age- and sex-matched healthy controls. Demographic and lung function data were evaluated. NT serum levels were determined by ELISA. RESULTS: NGF and BDNF levels were significantly increased in untreated asthmatics compared to the control and the treated group, while NT-3 demonstrated significantly higher levels in treated asthmatics compared to healthy controls. After stabilization of untreated subjects with ICS, the NT levels decreased significantly. CONCLUSIONS: These results suggest that NTs participate in allergic inflammation and asthma. Effective treatment leads to a decrease of circulating neurotrophic factors.     

Inflammatory markers and Acid-base equilibrium in exhaled breath condensate of stable and unstable asthma patients

Background: Nitrosative and acid stress play an important role in the pathogenesis of asthma. The aim of this study was to evaluate whether, in asthmatics, a link exists between the concentrations of nitrite/nitrate, ammonia and pH values in exhaled breath condensate (EBC) and asthma severity, lung function, exhaled nitric oxide (F(ENO)), total IgE, eosinophil cationic protein (ECP) and blood eosinophilia. Methods: The above-mentioned parameters were measured in 19 healthy volunteers and 91 allergic asthmatics divided into three groups, i.e. 22 subjects with steroid-na?ve stable asthma, 35 with inhaled corticosteroid (ICS)-treated stable asthma and 34 with ICS-treated unstable asthma. Results: Compared with healthy subjects, EBC from asthmatics had significantly lower pH values and ammonia concentrations and significantly higher levels of nitrite/nitrate. The extent of these changes was higher in patients with unstable than in patients with steroid-na?ve and stable ICS-treated asthma. The EBC pH was positively correlated with ammonia and negatively correlated with nitrite/nitrate, F(ENO) or blood eosinophilia in all three groups of asthmatics. Significant positive correlations between EBC nitrite/nitrate and blood eosinophilia, ECP levels or F(ENO) were observed in all groups of asthmatics. Significant negative correlations between EBC ammonia and nitrite/nitrate, F(ENO), ECP concentrations or blood eosinophilia were demonstrated in the groups of ICS-na?ve and ICS-treated stable asthmatics. Conclusions: In asthmatic patients there is a relationship between EBC pH, ammonia and nitrite/nitrate concentrations and other recognized markers of airway inflammation. EBC pH values, ammonia and nitrite/nitrate levels measured together may help to assess airway inflammatory status and asthma severity.     

Increased levels of vascular endothelial growth factor in induced sputum in asthmatic patients

BACKGROUND: Vascular endothelial growth factor (VEGF) is highly expressed in the airway of asthmatic patients. As VEGF increases airway vascular permeability, consequent thickening of the airway wall mucosa may lead to narrowing of the airway lumen. OBJECTIVE: We evaluated the relationship between VEGF levels in induced sputum and eosinophilic inflammatory profiles, and the degree of airway vascular permeability in asthmatic patients and we evaluated the effect of inhaled corticosteroids on VEGF levels in induced sputum. METHODS: Induced sputum specimens were obtained from 28 glucocorticosteroids free asthmatics and 11 healthy control subjects. We examined VEGF levels and airway vascular permeability index in induced sputum. After the initial sputum induction, 21 asthmatics received 8-week inhaled beclomethasone dipropionate (BDP, 800 micro g/day) therapy, then sputum induction was repeated. RESULTS: The VEGF levels in asthmatics were significantly higher than in healthy control subjects (P < 0.0001). The VEGF levels were negatively correlated with forced expiratory volume of 1 s (FEV1, % predicted, r = - 0.68, P < 0.001), the percentage of eosinophils (r = 0.51, P < 0.01) and ECP levels (r = 0.39, P < 0.05). Moreover, the VEGF levels were significantly correlated with airway vascular permeability index (r = 0.61, P < 0.001). After 8-week inhaled BDP therapy, the VEGF levels were significantly decreased compared to pretreatment levels (P < 0.0001) and the VEGF levels were significantly correlated with airway vascular permeability index even in post-treatment asthmatics (r = 0.62, P < 0.01). CONCLUSION: The VEGF levels in induced sputum were increased in asthmatics and its levels were associated with degree of airway narrowing and airway vascular permeability. These findings provide strong evidence that VEGF may play an important role in the pathogenesis of bronchial asthma.     

Evaluation of antigen specific IgE responses in Japanese asthmatics and non-asthmatics]

BACKGROUND: An increase in the prevalence of asthma does not seem to be comparable to the dramatic increase of atopy for the last two decades in Japan. Atopy is considered an important risk factor for asthma. It is, however, suggested that asthma itself may be responsible for the increased overall IgE responsiveness. We examined the significance of IgE responsiveness in asthma. METHODS: We studied 265 healthy controls and 275 patients with asthma. Total serum IgE levels and levels of antigen-specific IgE antibody to mite (D. farinae), cat, dog, timothy, and Candida spp. were determined. We defined atopy by positive RAST (>0.35UA/ml) or MAST scores (>1.0 lumicount) to at least one inhaled allergen. Frequencies of atopic subjects and frequencies of subjects sensitized to each allergen in atopic subjects were compared between the asthmatics and controls. All comparisons were made in younger (<41 yrs) and older (> = 41 yrs) groups, separately. RESULTS: In younger non-asthmatics, 76.5% (104/136) were atopic. The frequency of atopy was significantly higher in asthmatic subjects compared to non-asthmatics in both younger and older groups. In atopic subjects, older asthmatics were sensitized to animals more frequently than older controls. Although the frequency of subjects sensitized to mite did not differ between asthmatics and controls both in younger and older atopic subjects, asthmatics sensitized to mite had higher titers of specific IgE antibody to mite compared to those of controls sensitized to mite. Even non-atopic asthmatics had higher levels of total IgE compared to non-atopic controls. CONCLUSION: Our data may indicate that sensitization to animals and severer sensitizations to mite are risk factors for asthma. However, given the high prevalence of atopy in younger healthy controls, and increased levels of total serum IgE even in non-atopic asthmatics, our findings may reflect the increased overall IgE responsiveness that is inherent in asthma.     

Relation between exhaled carbon monoxide levels and clinical severity of asthma

Carbon monoxide (CO) can be detected in exhaled air and is increased in asthmatic patients not treated with corticosteroids. However, it is uncertain whether exhaled CO is related to severity of asthma. To study whether exhaled CO is related to severity of asthma in clinical courses, exhaled CO concentrations were measured on a CO monitor by vital capacity manoeuvre in 20 mild asthmatics treated with inhaled beta2-agonists alone, 20 moderate asthmatics treated with inhaled corticosteroids, and 15 stable asthmatics treated with high dose inhaled corticosteroids and oral corticosteroids once a month over 1 years. Exhaled CO concentrations were also measured in 16 unstable severe asthmatics who visited the hospital every 7 or 14 days for treatment with high dose inhaled corticosteroids and oral corticosteroids. The mean values of exhaled CO in severe asthma over 1 year were 6.7 +/- 9.5 p.p.m. (n = 31, mean +/- SD) and significantly higher than those of non-smoking control subjects (1.2 +/- 0.9 p.p.m., n = 20, P < 0.01). Exhaled CO concentrations in unstable severe asthmatics were significantly higher than those in stable severe asthmatics. However, exhaled CO concentrations in mild and moderate asthmatics did not differ significantly from those in non-smoking control subjects (P > 0.20). There was a significant relationship between the exhaled CO concentrations and forced expiratory volume in one second in all asthmatic patients. These findings suggest that exhaled CO concentrations may relate to the severity of asthma and measurements of exhaled CO concentrations may be a useful means of monitoring airway inflammation in asthma.     

The role of fibronectin in bronchoalveolar lavage fluid of asthmatic patients

Allergic and chronic inflammation of the airway is regarded as the main pathogenesis of bronchial asthma, in which adhesion of inflammatory cells requires the expression of adhesion molecules. Thus, to clarify the role of fibronectin (FN) in the airway inflammation of bronchial asthma, FN levels in plasma and bronchoalveolar lavage fluid (BALF) from bronchial asthmatics were determined. FN concentrations in plasma and BALF were measured by enzyme-linked immunosorvent assay (ELISA) in 17 asthmatic patients and 10 healthy controls to elucidate the role of FN in allergic inflammation. The mean FN/albumin (Alb) level in the BALF of asthmatic patients was 2.973 micrograms/mg, which was significantly higher than that of healthy controls (0.727 microgram/mg). Non-atopic asthmatics showed a significantly higher level of FN in their BALF in comparison with atopic asthmatics, although the ratio of FN to albumin showed no significant difference. FN levels in BALF correlated significantly with total cell density (r = 0.71, P < 0.05) and alveolar macrophage density (r = 0.64, P < 0.05). FN levels in plasma did not correlate with those in BALF. In conclusion, increased FN in BALF, which was produced locally in the airways of asthmatic patients, is actively involved in the regulation of allergic inflammation.     

Mannose binding lectin gene polymorphisms and asthma

BACKGROUND: Bronchial asthma is a chronic inflammatory disorder of the airways. Recently, it has been suggested that complement plays significant roles in asthma. Mannose-binding lectin (MBL) is one of the key molecules in complement activation pathways that are associated with several infectious and immune disorders. SUBJECTS AND METHOD: To investigate whether MBL plays roles in asthma, we analysed MBL2 polymorphisms (allele B, H/L and Y/X) and plasma MBL levels in a Japanese adult population including 232 healthy controls and 579 asthmatics. RESULTS: Although there was linkage disequilibrium among the three polymorphisms, each polymorphism significantly affects serum MBL levels independently. However, there were no significant differences between asthmatics and controls in MBL2 genotype distribution and in MBL concentrations [1.47+/-0.07(SE) mg/L for asthmatics and 1.66+/-0.14 mg/L for controls, P=0.2]. MBL levels and genotype have no significant relationship with serum IgE, pulmonary functions, and the severity of asthma. CONCLUSION: Although plasma MBL levels depend on the MBL2 polymorphisms, these polymorphisms and plasma MBL levels are not associated with the asthma phenotype.     

Levels of soluble IL-2 receptor in plasma from asthmatics. Correlations with blood eosinophilia, lung function, and corticosteroid therapy.

Evidence now suggests that eosinophils and T lymphocytes infiltrating bronchial tissues may play a key role in the pathophysiology of asthma. Circulating eosinophils, lung function, and plasma soluble IL-2 receptor (sIL-2R) were measured in 42 asthmatic patients referred for symptomatic asthma. The patients were divided into two groups based on the presence or absence of atopy. The group of non-atopic asthmatics was further divided according to the patients' requirement for long term oral corticosteroids. The mean sIL-2R +/- s.d. was 36.3 +/- 9.9 pM in the control group, 28.9 +/- 9.2 pM in the atopic asthmatics, 43.3 +/- 18.07 pM in the non-atopic asthmatics without oral steroid therapy, but was increased in the steroid-treated group (62.2 +/- 19.3 pM, P less than 0.01). A significant correlation was found between FEV1 and circulating eosinophils in atopic asthmatics and in non-atopic asthmatics without oral corticosteroid therapy, but not in the steroid-treated group. Furthermore, significant correlations were found between sIL-2R and FEV1, and between sIL-2R and blood eosinophils, in the group of non-atopic asthmatics not on oral steroid therapy. No such correlations were evidenced in the other groups of asthmatics. Similar results were obtained during the clinical course of three non-atopic patients followed for more than 1 year. These data suggest that T cell activation appears more prominent in non-atopic asthma than in atopic asthma. Moreover, it appears that T cell activation can occur in severe forms of asthma despite steroid treatment. Finally, the results suggest a possible link between T cell activation, eosinophils, and lung function, which may reflect a particular pathogenetic mechanism involved in non-atopic asthma.     

Plasma fibronectin in asthmatic patients and its relation to asthma attack

This study investigated the relation between asthma attacks and levels of plasma fibronectin (FN) and serum eosinophilic cationic protein (ECP) in patients with bronchial asthma in order to clarify the role of FN in the airway inflammation of bronchial asthma. Plasma levels of FN were significantly higher (P < 0.025) in patients with bronchial asthma than in healthy controls. They were also significantly higher (P < 0.05) in non-atopic asthmatics than in atopic asthmatics. Furthermore, plasma FN was lower during the attack than the non-attack stage (P < 0.025), and a significant increase of plasma FN was noted (P < 0.05) in asthmatics who had more severe and more frequent attacks. Serum levels of ECP were significantly higher during the attack than the non-attack stage (P < 0.005). An increase of plasma FN in the non-attack stage after attacks showed a significant correlation (P < 0.05) with a decrease of serum ECP. These observations clearly indicate that the decrease in plasma FN associated with attacks is closely related to aggravation of airway inflammation, and that the increase in plasma FN in the non-attack stage reflects chronic airway inflammation. These results suggest that the fluctuation in plasma levels of FN may be one of the factors affecting allergic inflammation and attacks in bronchial asthma.     

The effects of acute corticosteroid therapy for asthma on serum immunoglobulin levels

Immunoglobulin levels were followed in 21 nonsteroid-dependent asthmatics who required corticosteroids for an exacerbation of asthma. Twenty subjects who did not receive corticosteroids were used as controls. Baseline IgM and IgE levels were significantly higher in the corticosteroid-treated group. A fall in IgG level, maximal at 2 to 4 wk, was observed in the corticosteroid group, but not in control patients. Similarly, a significant fall in IgA was observed only in the corticosteroid group, maximal at 6 to 8 wk. There was no significant change in IgM levels in either group. Total IgE levels increased dramatically I wk after institution of corticosteroids. This was followed by a decrease to baseline or below at 6 to 8 wk. Changes in specific IgE antibody titers as measured by RAST technique revealed similar changes to those seen with total IgE. The results of the study indicate that asthma therapy with short-term corticosteroids can be associated with prolonged depressions of serum IgG, IgA levels and transient elevations of IgE levels, without apparent alterations of IgM levels.     

Plasma soluble human leukocyte antigen G levels in asthmatic children

BACKGROUND: Human leukocyte antigen G (HLA-G) is a nonclassical major histocompatibility complex class I gene. HLA-G stimulates Th2 cytokine secretion by peripheral blood mononuclear cells. The role of soluble HLA-G (sHLA-G) in bronchial asthma is incompletely understood and the plasma level of sHLA-G in asthmatic children has not been investigated. OBJECTIVE: It was the aim of this study to investigate the plasma level of sHLA-G in asthmatic children. METHODS: Asthmatic (n = 53) and healthy children (n = 16) were included in the study. Levels of sHLA-G were determined in plasma using ELISA. Spirometry, total immunoglobulin E and eosinophil counts were obtained and skin testing done with a battery of 25 antigens with appropriate positive and negative controls. RESULTS: No significant difference was observed in the plasma level of sHLA-G between the asthmatic and healthy children (p > 0.05). When we compared atopic asthmatics with healthy controls, we found significantly higher levels of sHLA-G in atopic asthmatics (p < 0.05). There was a significant difference in the peripheral blood eosinophil counts and total immunoglobulin E levels among the groups (p < 0.001). CONCLUSION: Our study shows that plasma sHLA-G levels do not differ between asthmatic children and healthy controls. However, higher plasma levels of sHLA-G in atopic asthmatics may suggest a role for sHLA-G in atopy. Further investigations are required to better define the mechanism of the production and the role of sHLA-G molecules observed in patients with asthma.     

Post-Effect of Air Quality Improvement on Biomarkers for Systemic Inflammation and Microparticles in Asthma Patients After the 2008 Beijing Olympic Games: a Pilot Study

This study’s aim was to investigate the post-effect of an air quality improvement on systemic inflammation and circulating microparticles in asthmatic patients during, and 2 months after, the Beijing Olympics 2008. We measured the levels of circulating inflammatory cytokines and microparticles in the peripheral blood from asthma patients and healthy controls during (phase 1), and 2 months after (phase 2) the Beijing 2008 Olympic Games. The concentrations of circulating cytokines (including TNFα, IL-6, IL-8, and IL-10) were still seen reduced in phase 2 when compared with those in phase 1. The number of circulating endothelial cell-derived microparticles was significantly lower during the phase 2 than that during phase 1 in asthma patients. The level of plasma lipopolysaccharide-binding protein (LBP) was significantly decreased in asthmatics in phase 2. The level of norepinephrine was significantly higher in phase 2 than that in phase 1 in plasma from both asthma patients and healthy subjects. There were no significant differences in the gene profile for the toll-like receptor (TLR) signaling from peripheral blood mononuclear cells. In vitro, microvesicles from patients with asthma impaired the relaxation to bradykinin and contraction to acetylcholine, whereas microparticles from healthy subjects did not. These data suggested that reduction in systemic pro-inflammatory responses and circulating LBP and increased level of norepinephrine in asthma patients persisted even after 2 months of the air pollution intervention. These changes were independent of the TLR signaling pathway. Circulating microparticles might be associated with airway smooth muscle dysfunction.     

Lower airways inflammation in allergic rhinitics: a comparison with asthmatics and normal controls

BACKGROUND: Allergic rhinitis (AR) and asthma represent a continuum of atopic disease. AR is believed to pre-dispose an individual to asthma. Compared with asthmatics and normal controls, the inflammatory response in the lower airways of rhinitics is not fully elucidated. To test the hypothesis that the inflammatory response in the airways of subjects with AR is at a level intermediate between that in normal controls and asthmatics, we have characterized bronchial inflammation and cytokine mRNA levels in non-asthmatic allergic rhinitics and compared it with subjects with allergic asthma and with normal controls. METHODS: Endobronchial mucosal biopsies were obtained at bronchoscopy from 14 allergic rhinitics, 16 asthmatics and 21 normal controls. Biopsies were embedded into glycol methacrylate resin for immunohistochemical analysis of cellular inflammation and snap frozen for semi-quantitative PCR analysis of cytokine mRNA levels. RESULTS: Airway inflammation in rhinitic subjects was characterized by an increase in submucosal eosinophils, mast cells and the mRNA expression of TNF-alpha, at an intermediate level between healthy and asthmatics. In addition, CD3(+) and CD8(+) lymphocytes in the epithelium, the endothelial expression of vascular adhesion molecule-1 and IL-1 beta mRNA were higher in the allergic rhinitics compared with both normal controls and asthmatics, whereas growth-related oncogene alpha-mRNA was decreased in AR compared with both healthy and asthmatics. Airway inflammation in the asthmatic group was characterized by higher numbers of eosinophils and mast cells, together with an increase in TNF-alpha-mRNA compared with both healthy and rhinitics. IFN-gamma mRNA was the highest in normal controls and lowest in the asthmatics. CONCLUSIONS: In individuals with AR the present data suggest an intermediate state of airway inflammation between that observed in normal individuals and subjects with clinical asthma. It is also indicated that IFN-gamma production by CD8(+) T lymphocytes could be protective against the development of airway hyperresponsiveness. Further work is needed to evaluate this hypothesis.