Allergen-induced asthma is characterized by airway eosinophilia and recruitment of helper T (Th) Type 2 lymphocytes. We hypothesized that lymphocyte-associated chemokines contribute to allergen-induced airway inflammation. Sixteen subjects with asthma were phenotyped according to their response to inhaled antigen as single- or dual-phase responders, and then underwent bronchoscopy and segmental allergen bronchoprovocation. Bronchoalveolar lavage fluids were obtained before and 48 hours after segmental challenge with allergen to determine the cellular response and patterns of Th1 and Th2 chemokines and cytokines. Airway cells, cytokines, and lymphocyte-associated chemokines increased after segmental challenge. Th2 chemokines (thymus and activation-regulated chemokine, macrophage-derived chemokine) correlated with airway eosinophils and concentrations of interleukin-5 and -13. In contrast, airway lymphocytes correlated with both Th2 and Th1 (monokine-induced by IFN-γ, IFN-γ–inducible protein-10) chemokines....

https://www.atsjournals.org/doi/pdf/10.1164/rccm.200312-1659OC

Enhanced Generation of Helper T Type 1 and 2 Chemokines in Allergen-induced Asthma

Background Asthma is a complex disease resulting from interactions between multiple genes and environmental factors. Study of gene-gene interactions could provide insight into asthma pathophysiology. Objective We investigated the interaction among 12 different loci in 8 candidate genes and asthma and increased plasma total IgE concentrations in 240 Chinese asthmatic subjects and 140 control subjects. Methods Genotyping was performed by means of RFLP analysis. Multifactor dimensionality reduction and logistic regression were used to analyze gene-gene interactions. Results A significant interaction was found between R130Q in the IL-13 gene ( IL13 ) and I50V in the IL-4 receptor α gene ( IL4RA ) on the risk of asthma, with a cross-validation consistency of 10 of 10 and a prediction error of 33.7% ( P = .014). The odds ratio of the high-risk to low-risk group was 2.6 (95% CI, 1.4-5.0; P = .004). For increased plasma total IgE concentration, the best 2-locus model consisted of R130Q in IL13 and C-431T in the thymus and activation-regulated chemokine gene ( TARC ). This model showed a maximum cross-validation consistency of 10 and a minimum prediction error of 36.1% ( P = .022). The odds ratio of the high-risk to low-risk group was 3.9 (95% CI, 2.0-7.7; P = .0001). Logistic regression revealed significant interactions between IL13 and IL4RA for asthma ( P = .042) and IL13 and TARC for increased total IgE concentration ( P = .012). Conclusions Our data suggest significant interactions between IL13 and IL4RA for asthma and IL13 and TARC for increased plasma total IgE concentrations in Chinese children.

https://www.jacionline.org/article/S0091-6749(05)02117-2/pdf

Gene-gene interactions for asthma and plasma total IgE concentration in Chinese children

Exhaled breath condensate (EBC) pH appears to be a robust measure of asthma However, the association between EBC pH and clinical factors and airway inflammatory markers remains unclear The objectives of this study were to investigate the factors determining EBC pH in asthmatic children, and the reproducibility and effects of collection devices on EBC pH in nine healthy, nonsmoking adults EBC was collected once from asthmatic children using EcoScreen, and from adults over 3 consecutive days using both RTubes and EcoScreen EBC pH was measured immediately in non-deaerated samples by microelectrode pH meter Concentrations of 8-isoprostane, cysteinyl leukotrienes (cys-LT), and leukotriene B4 (LTB4) were measured using enzyme immunoassay Exhaled nitric oxide concentration (FeNO) was measured by chemiluminescence Fifty-eight asthmatics (16 intermittent, 12 mild persistent, and 30 moderate-to-severe persistent) were recruited EBC pH was lower among patients with moderate-to-severe persistent than intermittent asthma (P = 0046) This marker correlated inversely with disease severity score (ρ = −0276, P = 0036), but not FeNO or other EBC biomarkers Bland-Altman analyses found pH but not other EBC biomarkers to be reproducible, which were confirmed by its low coefficient of variation (27%; range, 04–52%) There was poor correlation between pH in EBC collected by RTube and EcoScreen (ρ = 0059, P = 0784) Factor analysis selected four factors that explained 675% of the total variance, and EBC pH clustered with both cys-LT and LTB4 In conclusion, our results suggest that pH in non-deaerated EBC is influenced by asthma severity in children EBC pH measurement is reproducible, but is dependent on the collection devices used Pediatr Pulmonol © 2005 Wiley-Liss, Inc

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ppul.20296

Clinical and technical factors affecting pH and other biomarkers in exhaled breath condensate.

The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) is a challenge. Thymus- and activation-regulated chemokine (TARC) has recently been reported to play a role in ABPA. The aim of this study was to compare the diagnostic value of TARC with that of known serological markers for diagnosis of ABPA in CF patients. The present study longitudinally followed 48 CF patients, of whom 12 had a diagnosis of ABPA according to Nelson's criteria, for 1-8 yrs with repeated measurements of serum total immunoglobulin (Ig)E, specific Aspergillus fumigatus IgE and IgG, specific IgE against recombinant A. fumigatus allergens (rAsp f) 1, 3, 4 and 6, and TARC. Median (interquartile range) TARC levels were 589 (465-673) pg x mL(-1) in ABPA patients and 232 (189-289) pg x mL(-1) in non-ABPA patients. Receiver operating characteristic curves revealed that TARC was superior to the other markers for diagnosis of ABPA. Diagnostic accuracy was greater for TARC (93%) than for total IgE (74%), or rAsp f 4 (75%) or f 6 (79%). The present study indicates that thymus- and activation-regulated chemokine may be useful in the diagnosis of allergic bronchopulmonary aspergillosis in cystic fibrosis patients. However, larger studies are needed before thymus- and activation-regulated chemokine can routinely be used in diagnostic algorithms.

https://erj.ersjournals.com/content/erj/31/1/36.full.pdf

Comparison of serum markers for allergic bronchopulmonary aspergillosis in cystic fibrosis

Background: Recent studies have repeatedly shown weak correlations among lung function parameters, atopy, exhaled nitric oxide level (FeNO), and airway inflammatory markers, suggesting that they are non-overlapping characteristics of asthma in adults. A study was undertaken to determine, using factor analysis, whether the above features represent separate dimensions of childhood asthma. 

Methods: Clinically stable asthmatic patients aged 7–18 years underwent spirometric testing, methacholine bronchial challenge, blood sampling for atopy markers and chemokine levels (macrophage derived chemokine (MDC), thymus and activation regulated chemokine (TARC), and eotaxin), FeNO, and chemokines (MDC and eotaxin) and leukotriene B4 measurements in exhaled breath condensate (EBC). 

Results: The mean (SD) forced expiratory volume in 1 second (FEV1) and FeNO of 92 patients were 92.1 (15.9)% predicted and 87.3 (65.7) ppb, respectively. 59% of patients received inhaled corticosteroids. Factor analysis selected four different factors, explaining 55.5% of total variance. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.587. Plasma total and specific IgE levels, peripheral blood eosinophil percentage, and FeNO loaded on factor 1; plasma TARC and MDC concentrations on factor 2; MDC, eotaxin and leukotriene B4 concentrations in EBC on factor 3; and plasma eotaxin concentration together with clinical indices including body mass index and disease severity score loaded on factor 4. Post hoc factor analyses revealed similar results when outliers were excluded. 

Conclusions: The results suggest that atopy related indices and airway inflammation are separate dimensions in the assessment of childhood asthma, and inflammatory markers in peripheral blood and EBC are non-overlapping factors of asthma.

https://thorax.bmj.com/content/thoraxjnl/60/10/822.full.pdf

Clinical and atopic parameters and airway inflammatory markers in childhood asthma: a factor analysis

Recent studies suggested the T-helper cells type-2 lymphocytes-specific thymus and activation-regulated chemokine (TARC) and monocyte-derived chemokine (MDC) are useful inflammatory markers for chronic asthma. However, their roles in assessing the severity of acute asthma are unknown. This study aims to evaluate the serial changes of plasma TARC and MDC concentrations in children with asthmatic exacerbation. All patients with acute asthma were treated with systemic corticosteroid for 5 days. The severity of asthmatic exacerbation was classified according to the Global Initiative for Asthma guidelines. Plasma TARC and MDC concentrations were measured by sandwich enzyme immunoassays. Sixteen children, with a median (interquartile range) age of 9.3 (7.2–10.6) yrs and asthmatic exacerbation, were recruited. Plasma TARC concentration showed inverse correlation with peak expiratory flow rate at presentation. The median plasma TARC concentration was highest during the acute attacks (46 pg·mL −1 ) as compared to those levels at 1 (31 pg·mL −1 ) and 5 weeks (32 pg·mL −1 ) following treatment. The median plasma MDC level similarly decreased from 698 pg·mL −1 at baseline to 261 pg·mL −1 1 week later, but increased back to 574 pg·mL −1 at 5 weeks. These results suggest that plasma T-helper cells type-2 lymphocytes-specific thymus and activation-regulated chemokine but not monocyte-derived chemokine concentration may be a useful inflammatory marker in assessing asthmatic exacerbation in children.

https://erj.ersjournals.com/content/erj/21/4/616.full.pdf

Plasma TARC concentration may be a useful marker for asthmatic exacerbation in children

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Plasma TARC concentration may be a useful marker for asthmatic exacerbation in children