Serum Periostin Level in Children with Asthma

Objectives To determine the average serum periostin level in children with asthma between 6 and 16 y of age, and to fnd out if the levels correlated with markers of eosinophilic infammation, asthma control, and severity. Methods Children under follow-up at a tertiary care centre were enrolled. Children with conditions causing elevated serum periostin other than asthma, or history of systemic steroid use in the past 6 mo were excluded. Serum total IgE and periostin were estimated by ELISA. Results The median (IQR) serum periostin level was 52.6 (45.4, 58.3) ng/mL. Levels did not vary with age, gender, duration of symptoms, positive family history, or history of exacerbations in the last 6 mo. There was no signifcant correlation with anthropometric parameters or their z scores, or markers of eosinophilic infammation in blood including serum total IgE, eosinophil percentage or absolute eosinophil count. There was no diference in median periostin levels of children with diferent asthma symptom control or asthma severity. Conclusions In a group of 26 Indian children with physician-diagnosed asthma, serum periostin showed no signifcant correlation to markers of eosinophilic infammation.

Role of eosinophilic inflammation and atopy in elderly asthmatic patients

BACKGROUND: Asthma in the elderly is severe and associated with poor treatment outcome. Although atopy has an important role in pathogenesis, its role in the elderly is unclear, partly due to immune senescence. OBJECTIVE: We aimed to examine the associations of Th2-mediated inflammation with asthma severity in the elderly. METHODS: Consecutive asthmatics older than 60 years without severe exacerbation within 8 weeks were enrolled. Atopic status was determined by positive serum specific IgE or skin prick test to common aeroallergens. Serum total IgE was measured simultaneously to exhaled fractional concentration of nitric oxide (FeNO). Asthma control level was assessed by using Thai Asthma Control Test (ACT) score. RESULTS: Total of 44 elderly asthmatic patients were enrolled. The mean age was 68.9 years and mean age of asthma diagnosis was 46.6 years. Seventy-seven percent of patients were female. Atopic status was found in 45.5% of patients. Uncontrolled asthma classified as ACT score < 20 was noted in 25% of elderly asthma, but its association with either high serum total IgE (≥120 IU/mL), high FeNO (≥50 ppb) or atopic status was not detected. CONCLUSION: One-fourth of elderly asthmatics were clinically uncontrolled, while atopy was confirmed in 45.5%. Neither high total IgE, high FeNO nor atopic status was associated with uncontrolled asthma in the elderly. Other factors might play role in asthma severity in the elderly, and has to be further investigated.

Fractional exhaled nitric oxide in Korean children with allergic rhinitis

PURPOSE: Fractional exhaled nitric oxide (FeNO) is useful for the diagnosis of allergic rhinitis (AR) as well as bronchial asthma (BA). However, FeNO may differ according to race, age, and other determinants. There have been few studies about FeNO in Korean children with AR. The aims of this study were to evaluate the value of FeNO in AR and to compare FeNO, and determinants of FeNO levels between AR, BA, and combined AR and BA. METHODS: This study included 647 children aged 5 to 17. The children were classified into 5 groups after performing the skin test, FeNO measurement, the pulmonary function test, and the methacholine challenge test: those with nonallergic rhinitis (NAR), those with AR, those with BA, and those with combined AR and BA, and healthy controls,. RESULTS: The values of FEV1 (forced expiratory volume in one second) %predicted were 94.4%+/-12.6%, 93.8%+/-20.7%, 90.0%+/-17.4% in AR, BA, and combined AR and BA, respectively. The values of FeNO in AR (32.3+/-25.0 ppb), BA (31.1+/-20.5 ppb), and combined AR and BA (34.5+/-30.4 ppb) were significantly higher compared to those of NAR (16.8+/-13.5 ppb) and controls (15.9+/-12.5 ppb). There was no significant difference in FeNO among AR, BA, and combined AR and BA. FeNO was significantly higher in patients with > or =4 positive results (36.6+/-29.2 ppb) than in those with <4 positive skin test results (27.6+/-20.7 ppb). When the receiver operating characteristic curve analysis for prediction of AR showed 0.756 of area under the curve, the cutoff level of FeNO was 16 ppb. CONCLUSION: In this study, children with AR had increased levels of FeNO. It is suggested that AR may have eosinophilic bronchial inflammation without BHR or clinical asthma.

A genetic effect of IL-5 receptor alpha polymorphism in patients with aspirin-exacerbated respiratory disease

Persistent eosinophil activation in both the upper and lower airway mucosa is a central feature of aspirin-exacerbated respiratory disease (AERD). Eosinophil activation and survival are profoundly influenced by interleukin 5 (IL-5) and its receptor, IL-5R. In patients susceptible to allergic disorders, IL-5 receptor alpha (IL5RA) polymorphisms have been reported; however, an association with AERD remains unclear. We hypothesize that IL5RA polymorphisms may contribute to eosinophil activation in AERD patients. We recruited 139 AERD patients, 171 aspirin-tolerant asthma patients and 160 normal controls. IL5RA polymorphisms (-5993G>A, -5567C>G and -5091G>A) were genotyped and functional activity of polymorphism was assessed by luciferase reporter assay and electrophoretic mobility shift assay (EMSA). There was no significant difference in the genotype frequency of the three polymorphisms among the three groups. AERD patients carrying the AA genotype at -5993G>A had a significantly higher presence of serum-specific immunoglobulin E (IgE) to staphylococcal enterotoxin A (P=0.008) than those with the GG/GA genotype. In vitro, the -5993A allele had a higher promoter activity compared with the -5993G allele in human mast cell (HMC-1; P=0.030) and human promyelocytic leukemia (HL-60; P=0.013) cells. In EMSA, a -5993A probe produced a specific shifted band than the -5993G had. These findings suggest that a functional polymorphism in IL5RA may contribute to eosinophil and mast cell activation along with specific IgE responses to staphylococcal enterotoxin A in AERD patients.

IL-5 Promoter Polymorphism Enhances IgE Responses to Staphylococcal Superantigens in Adult Asthmatics

Interleukin 5 (IL-5) is a key cytokine involved in the induction of T-helper type 2 (Th2) responses in the asthmatic airway. We investigated IL-5 genetic polymorphisms associated with asthma phenotypes, including IgE responses to staphylococcal enterotoxins A and B (SEA and SEB, respectively), in asthmatics. Adult asthmatics (n=310) and normal controls (n=160) were enrolled in the present study. Serum total and specific IgE to SEA and SEB were measured. Two IL-5 polymorphisms, -746A>G and +4499T>G, were genotyped using the primer-extension method. There were no significant differences in genotype or haplotype frequencies of these polymorphisms between the two groups. Asthmatics carrying the AG/GG genotype at -746A>G had a significantly higher prevalence of serum specific IgE to SEA (P=0.008), higher total IgE levels (P=0.014), and lower PC20 methacholine levels (P=0.002) compared to those with the AA genotype. These findings suggest that the IL-5 promoter polymorphism at -746A>G enhances serum total and specific IgE responses to SEA, which may augment airway hyperresponsiveness in adult asthmatics.

IL-13 Gene Polymorphisms are Associated With Rhinosinusitis and Eosinophilic Inflammation in Aspirin Intolerant Asthma

PURPOSE: Aspirin-intolerant asthma (AIA) is characterized by moderate to severe asthma that is aggravated by aspirin or other non-steroidal anti-inflammatory drugs. Affected patients frequently have chronic rhinosinusitis and nasal polyposis due to persistent upper and lower airway inflammation with marked eosinophilia. IL-13 plays a crucial role in the development of allergic asthma by inducing airway eosinophilia and hyper-reactivity and it has been correlated with an increased eosinophil count. METHODS: Two promoter polymorphisms of the IL-13 gene (-1510 A>C and -1055C>T) and one coding nonsynonymus Arg110Gln (110G>A) polymorphism were genotyped using primer extension methods in 162 patients with AIA, 301 patients with aspirin-tolerant asthma (ATA), and 430 normal healthy controls (NC). RESULTS: There was no significant difference in the genotype, allele, and haplotype frequencies of the three polymorphisms among the three groups. AIA patients with the AA genotype -1510A>C (P=0.012) and CC genotype -1055C>T (PA). CONCLUSIONS: These findings suggest that the IL-13 polymorphisms at -1510A>C and 1055C>T are associated with the development of rhinosinusitis in AIA patients. IL-13 Arg110Gln may be associated with an increased eosinophil count and eotaxin-1 level and could increase eosinophilic inflammation in the upper and lower airways of patients with AIA.

IL-13 Gene Polymorphisms are Associated With Rhinosinusitis and Eosinophilic Inflammation in Aspirin Intolerant Asthma

PURPOSE: Aspirin-intolerant asthma (AIA) is characterized by moderate to severe asthma that is aggravated by aspirin or other non-steroidal anti-inflammatory drugs. Affected patients frequently have chronic rhinosinusitis and nasal polyposis due to persistent upper and lower airway inflammation with marked eosinophilia. IL-13 plays a crucial role in the development of allergic asthma by inducing airway eosinophilia and hyper-reactivity and it has been correlated with an increased eosinophil count. METHODS: Two promoter polymorphisms of the IL-13 gene (-1510 A>C and -1055C>T) and one coding nonsynonymus Arg110Gln (110G>A) polymorphism were genotyped using primer extension methods in 162 patients with AIA, 301 patients with aspirin-tolerant asthma (ATA), and 430 normal healthy controls (NC). RESULTS: There was no significant difference in the genotype, allele, and haplotype frequencies of the three polymorphisms among the three groups. AIA patients with the AA genotype -1510A>C (P=0.012) and CC genotype -1055C>T (PA). CONCLUSIONS: These findings suggest that the IL-13 polymorphisms at -1510A>C and 1055C>T are associated with the development of rhinosinusitis in AIA patients. IL-13 Arg110Gln may be associated with an increased eosinophil count and eotaxin-1 level and could increase eosinophilic inflammation in the upper and lower airways of patients with AIA.

The Role of TNF-alpha in Eosinophilic Inflammation of RSV Bronchiolitis / 소아알레르기및호흡기학회지

PURPOSE: Tumor necrosis factor (TNF)-alpha and eosinophilic inflammation have their role in asthma, but there were no studies on respiratory syncytial virus (RSV) bronchiolitis. The aim of our study was to investigate whether TNF-alpha has a role in eosinophilic inflammation of lower respiratory tract infections with RSV and has the correlation with other cytokines. METHODS: Fifty children with first RSV bronchiolitis (RSV group) and 18 healthy children without any respiratory symptom and sign (control group) were enrolled. Clinical data, such as eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), were analyzed. We measured interleukin (IL)-5, IL-8, TNF-alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-gamma, eotaxin, and regulated on activation, normal T cell expressed and secreted (RANTES) in nasal lavage fluid in both groups. RESULTS: Eotaxin, GM-CSF, IL-8, IFN-gamma and TNF-alpha were higher in the RSV group than the control group. TNF-alpha correlated with an eosinophil-active cytokine, GM-CSF (r=0.86, P<0.0001), IFN-gamma (r=0.90, P<0.0001), and with eosinophil-active C-C chemokines such as eotaxin (r=0.50, P<0.0001). TNF-alpha also correlated with proinflammatory cytokines such as IL-8 (r= 0.81, P<0.0001). CONCLUSION: TNF-alpha correlated with eosinophil-active chemokines and cytokines. Therefore, TNF-alpha may have a role in eosinophilic inflammation in children with RSV bronchiolitis.

Role of IL-5 and eotaxin in airway eosinophilic inflammation / 천식및알레르기

BACKGROUND: IL-5 and eotaxin are the most important cytokines/chemokines responsible for regulating eosinophil locomotion. OBJECTIVE: We investigated the role of IL-5 and eotaxin in airway eosinophilic inflammation in patients with chronic cough by analyzing sputum from patients. METHODS: Thirty-one patients who had chronic cough and seven normal control subjects were enrolled. Patients were divided into two groups, asthma group (n=15) and non-asthma group (n=16). Sputum was induced by inhalation of hypertonic saline. Total cell counts and differentials were determined. The levels of IL-5 and eotaxin were measured by ELISA, and the levels of EDN and MBP were measured by RIA. RESULTS: Patients in the asthma group showed higher percentage of eosinophils and higher levels of EDN and IL-5 (P<.001, P<.05 and P<.05, respectively) compared to subjects in the control group and higher % eosinophils, higher levels of EDN and MBP (P<.001, P<.05 and P<.05, respectively) compared to subjects in the control group. Non-asthma group patients also showed higher percentage of eosinophils and increased IL-5 levels (P<.05 and P<.05, respectively) compared to the control group. The eotaxin level correlated positively with percentage of eosinophils (Rs = 0.60, P<.001), the EDN (Rs = 0.59, P<.001) and MBP (Rs = 0.73, P<.01) levels, and correlated inversely with FEV1 % pred. (Rs = -0.71, P<.01). Unexpectedly, the IL-5 levels did not correlate significantly with any of sputum eosinophil indices or FEV1 % pred. CONCLUSION: Good correlation of eotaxin with sputum eosinophil indices or pulmonary function and no correlation of IL-5 with them suggest that eotaxin may play a more important role in the specific recruitment and degranulation of airway eosinophils, although both IL-5 and eotaxin are involved in local eosinophilic inflammation.

Evaluation of airway inflammation using induced sputum in adult patients with bronchial asthma / 천식및알레르기

OBJECTIVES: This study was performed to investigate the relationship between cell counts, supernatant and lysate ECP levels in sputum, and physiologic markers in adult asthmatics. METHODS: Twenty-two patients with mild to moderate persistent asthma, ten patients with acute exacerbated asthma and nine healthy subjects were enrolled. Sputum was induced by inhalation of hypertonic saline, and homogenized with 0.1% dithiothreitol. A total and differential cell was measured. The remnant cell suspension was centrifuged, and ECP (supernatant ECP) was measured in supernatant fluid. Cell pellet was reacted with a cellular lysis buffer to release cell-associated ECP, and ECP (lysate ECP) was measured again in supernatant fluid. The ratio of supernatant to lysate ECP was calculated as an index of eosinophil degranulation. Spirometry and methacholine bronchial challenge tests were also performed as physiological markers of asthma. RESULTS: The patients with acute exacerbated asthma showed significantly higher percentage of sputum neutrophil, eosinophil count, concentration of sputum supernatant ECP and ratio of supernatant to lysate ECP than those of normal controls and stable asthmatic patients(p < 0.05, respectively). The level of sputum supernatant ECP, supernatant/lysate ECP ratio, and percentage of neutrophil showed negative correlations with pulmonary functions, but no correlations with a degree of bronchial hyperresponsiveness. There was no significant correlations between of serum ECP level and physiological parameters. CONCLUSION: These results suggest that both neutrophils and eosinophils play roles in the exacerbation of asthma. The sputum supernatant/lysate ECP ratio might be valuable in assessment of activation status of eosinophils in various hypereosinophilic conditions or diseases.