The Immunology of Asthma (original) (raw)
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Increases in airway eosinophilia and a th1 cytokine during the chronic asymptomatic phase of asthma
Respiratory Medicine, 2010
Background-Studies using allergen challenge models have suggested Th2 cytokines promote airway inflammation in asthma. We assessed mediators of airway inflammation during the chronic asymptomatic phase of asthma. Methods-Nine non-atopic asthma (NAA) patients, 19 atopic asthma (AA) patients, 20 atopic controls (AC), and 38 normal controls (NC) underwent sputum induction while asymptomatic. Sputum total cell counts and differentials were determined; levels of cytokines IL-4, IL-5, IL-13, GM-CSF, and IFN-γ, and chemokines eotaxin (CCL11) and RANTES (CCL5) were measured by ELISA; and levels of eosinophil-derived neurotoxin (EDN) were measured by radioimmunoassay. Results-NAA patients showed higher % eosinophils and total eosinophils compared to AA. NAA and AA patients showed higher IFN-γ and EDN levels compared to AC and NC, with no differences in IL-4, IL-5, or IL-13 levels among the four groups. GM-CSF levels were higher in AA patients compared to AC or NC. In NAA, AA, and AC patients, % eosinophils and EDN levels correlated positively with IFN-γ, GM-CSF, eotaxin, and RANTES, but not with IL-5 levels. Conclusions-Baseline airway inflammation of intrinsic and extrinsic asthma is characterized by eosinophilic inflammation and the Th1 cytokine, IFN-γ. GM-CSF, instead of IL-5, and chemokines may coordinate airway eosinophilia during the chronic asymptomatic phase of asthma.
“T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin
European Respiratory Journal
Type-2 (T2) immune responses in airway epithelial cells (AECs) classifies mild–moderate asthma into a T2-high phenotype. We examined whether currently available clinical biomarkers can predict AEC-defined T2-high phenotype within the U-BIOPRED cohort.The transcriptomic profile of AECs obtained from brushings of 103 patients with asthma and 44 healthy controls was obtained and gene set variation analysis used to determine the relative expression score of T2 asthma using a signature from interleukin (IL)-13-exposed AECs.37% of asthmatics (45% nonsmoking severe asthma, n=49; 33% of smoking or ex-smoking severe asthma, n=18; and 28% mild–moderate asthma, n=36) were T2-high using AEC gene expression. They were more symptomatic with higher exhaled nitric oxide fraction (FeNO) and blood and sputum eosinophils, but not serum IgE or periostin. Sputum eosinophilia correlated best with the T2-high signature. FeNO (≥30 ppb) and blood eosinophils (≥300 cells·µL−1) gave a moderate prediction of T...
Journal of Allergy and Clinical Immunology, 2002
Background: Asthma is characterized by variable airflow obstruction and airway hyperresponsiveness in association with airway inflammation under the influence of T H 2 cytokines. Eosinophilic bronchitis has similar immunopathology to asthma but without disordered airway physiology. Whether eosinophilic bronchitis is associated with increased expression of T H 2 cytokines is unknown. Objective: We sought to assess the expression of T H 2 cytokines in eosinophilic bronchitis. Methods: Expression of activation markers and chemokine receptors from blood and bronchoalveolar lavage (BAL) fluid T cells and the T H 2 cytokine expression from these T cells and bronchial mucosa biopsy specimens were assessed from subjects with eosinophilic bronchitis, subjects with asthma, and healthy control subjects. Results: The proportion of resting (stimulated) CD4 BAL fluid T cells expressing intracellular IL-4 was significantly higher in the subjects with eosinophilic bronchitis 7.2% (11.4%) and subjects with asthma 5.3% (5.5%) than in healthy control subjects 2.8% (3.9%) (P = .03). The number of IL-4 + (P < .001) and IL-5 + (P = .003) cells per square millimeter of bronchial submucosa was significantly higher in the disease groups than in the healthy control subjects. Expression of intracellular IFN-γ was significantly higher in stimulated blood CD8 T cells from subjects with eosinophilic bronchitis (24%) and asthma (17%) than in the healthy control subjects (5%; P = .003). There were no between-group differences in expression of IFN-γ in the BAL fluid T cells or in the bronchial submucosa and no differences in expression of activation markers or chemokine receptors. Conclusion: These findings support the concept of asthma as a disease associated with activation of T H 2 lymphocytes in the airway and provide evidence that these cytokines play a role in the development of airway inflammation in eosinophilic bronchitis but suggest that the release of T H 2 cytokines is not sufficient for the elaboration of disordered airway physiology in asthma. (J Allergy Clin Immunol 2002;110:899-905.)
Journal of Investigational Allergology and Clinical Immunology, 2019
Background: Although blood eosinophils are currently recognized as the main clinical marker of T H 2-type inflammation, their relevance in identifying asthma severity remains a matter of debate. Methods: Our retrospective real-life study on severe asthmatics included in the NEONet Italian database aimed to investigate the relevance of blood eosinophil count and fractional exhaled nitric oxide (FeNO) in the clinical assessment of severe asthma and their role as potential predictors of responsiveness to anti-IgE therapy. The cutoff values chosen were 300 eosinophils/mm 3 and FeNO of 30 ppm. Results: We evaluated 132 adult patients. No significant differences were observed between the groups (high and low baseline eosinophil counts) in terms of demographic data, total IgE, lung function, patient-reported outcomes, or nasal comorbidities. The Asthma Control Test score and Asthma Quality of Life Questionnaire scores were poorer in patients with FeNO ≥30 ppb than in patients with FeNO <30 ppb. In the high FeNO subgroup, more frequent hospital admissions and a higher number of working days lost in the previous year were registered. A combined score including both eosinophils and FeNO did not improve the accuracy of the individual parameters. In the high-eosinophil subgroup, the proportion of responders to omalizumab was greater and increased at each follow-up time point. Conclusions: Our findings show that blood eosinophil count is not an unequivocal marker of asthma severity, whereas a higher FeNO level is associated with more frequent hospital admissions and more working days lost. Blood eosinophils seem to act as a predictor of response to omalizumab.
Assessment of the Th1/Th2 Paradigm in Whole Blood in Atopy and Asthma
American Journal of Respiratory and Critical Care Medicine, 2000
Atopy is characterized by an immune system that is biased to T helper cell, type 2 (Th2) activation. This condition predisposes to asthma, a disease in which a Th2 activation was found in blood and lungs. However, most blood studies have considered purified cells, which might give an incomplete view of immune reactions. In this study, we assessed in whole blood cultures the Th1/Th2 paradigm in atopy and asthma. Sixty-nine subjects (31 atopic asthmatics, six nonatopic asthmatics, 13 atopic nonasthmatics, and 19 control subjects) were included in this study. Interleukin-4 (IL-4), interferon gamma (IFN-␥), and IL-12 were assayed in stimulated whole blood culture supernatants by using a flow cytometer microsphere-based assay. Intracellular IL-4 and IFN-␥ were detected in T cells and CD8 ϩ T cells by flow cytometry. Atopy was characterized by a higher production of IL-4, which was correlated to total IgE levels, and by an impairment of the T-cell capacity to produce IFN-␥. This impairment was correlated to the number of positive skin tests. In asthma, the overproduction of IL-4 was still found if atopy was present. Unexpectedly, an overproduction of IFN-␥ was found, which was related to an increased capacity of CD8 ϩ T cells to produce IFN-␥. The number of IFN-␥-producing CD8 ϩ T cells was related to asthma severity, to bronchial hyperresponsiveness, and to blood eosinophilia. In addition, this number was correlated to IL-12 production. These results show that in addition to the well-known Th2 inflammation in asthma, there are IFN-␥-producing CD8 ϩ T cells in the blood, possibly controlled by IL-12.
Role of Th2 type Cytokines and IgE in Asthmatic Children
Biomedical and Pharmacology Journal
Bronchial asthma (BA) is usually persistent through allergic sensitization, which is likely to result in bronchial hyper-responsiveness and acute bronchoconstriction due to reactions to specific and non-specific trigger stimuli. Many research focused on the role of T cells; particularly, T helper 2 (Th2) cells which linked to controlling immunoglobulin E (IgE) production due to their role in producing different cytokines, like Interleukin-13 (IL-13), in addition to influencing the function of eosinophils through the actions of IL-5. From this perspective, we decided to study the role of IgE, IL-13, and IL-5 in asthmatic children. IL-5, IL-13, and total IgE have been measured by ELISA technique in the serum of 57 children with bronchial asthma and compared to that of 20 healthy controls. Our results reported that 38/57 (66.67%) of the patient group had a family history for allergy, and parental consanguinity was found in 4/57 families (0.07%). IgE levels showed high statistical signi...
Journal of Allergy and Clinical Immunology, 1996
Cellular and mediator profiles in bronchoalveolar lavage have not been compared systematically between patients with asthma of different severities, mainly because the patients' with more severe asthma have an increased need for antiinflammatory medication. Information is limited to comparisons of allergic and intrinsic asthma, which can be distinguished clinically. When patients from these two groups with similar degrees of" bronchial hyperresponsiveness were compared, both groups showed increased numbers" of activated Thelper lymphocytes; those in the allergic group expressed the IL-2
Cellular and immunological markers of allergic and intrinsic bronchial asthma
Lung, 1994
Based on a growing body of evidence, allergic as well as intrinsic bronchial asthma have recently been defined as chronic persistent inflammatory disorders. Agreement has been reached that asthma can no longer be equated with bronchospasm only, and that the absence of reversibility of airflow obstruction does not exclude bronchial asthma. Bronchial hyperreactivity, on the other hand, although common to the vast majority of asthmatics, is not specific for bronchial asthma and provocation tests to measure bronchial hyperreactivity are not suited for routine monitoring of bronchial asthma. The clinical features of asthma are related to cellular as well as to soluble parameters of bronchial inflammation. Therefore, means of assessing and monitoring asthmatic inflammation have been investigated. Since eosinophils, T lymphocytes, mast cells, macrophages, neutrophils, epithelial cells, and structural cells, as well as various proinflammatory mediators and proteins, have been implicated in the pathogenesis of bronchial asthma, it has been anticipated that several of these cells or mediators might be either diagnostic of bronchial asthma or could serve as markers to monitor the underlying bronchial inflammation. Currently there is no diagnostic marker of bronchial asthma, which, on its own, either confirms or excludes bronchial asthma with appropriate sensitivity and specificity. Clinically the most reliable feature of bronchial asthma that seems to be related closely to the symptomatology still is the presence of eosinophits in peripheral blood, and especially in sputum. Eosinophil-derived products, particularly eosinophil granule proteins, have been investigated as markers of eosinophil participation in the pathogenesis of asthma and, comparable to eosinophil numbers themselves, are possible predictors of impending exacerbations of allergic, as well as intrinsic bronchial asthma. However, clinically their precise value in diagnosing and monitoring of bronchial asthma has not been documented Offprint requests to: J.-C. Virchow, Jr. J.-C. Virchow, Jr. et al. convincingly and requires further investigation. Increasing data suggest that the regulation of eosinophilia is largely conveyed by interleukin-5 (IL-5) released from activated T-helper lymphocytes and possibly other cells. Therefore, T-lymphocyte activation, and especially assessment of systemic and local IL-5 levels, might be of diagnostic value and possibly useful in monitoring of inflammation in bronchial asthma in the future. A possible role and future applications for other markers of inflammation not related to eosinophils in monitoring or diagnosing bronchial asthma need to be established.