Asthma Exacerbations after Glucocorticoid Withdrawal Reflects T Cell Recruitment to the Airway

Castro, Mario; Bloch, Sharon; Jenkerson, Michelle V.; DeMartino, Steve; Hamilos, Daniel L.; Cochran, Rebecca; Zhang, Xueping E. Liang; Wang, Haochuan; Bradley, Joseph P.; Schechtman, Kenneth B.; Holtzman, Michael J.

doi:10.1164/rccm.200208-960oc

Cited by 50 publications

(40 citation statements)

References 58 publications

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“…In the study of Pizzichini et al (66) sputum eosinophil counts were raised several weeks before the increase in symptoms and reduction in FEV 1 . Likewise, Castro et al (67) showed that progressive withdrawal of inhaled corticosteroids led to an increase in bronchial eosinophilia and bronchial infiltration by T-cells (CD8+ or CD4+) associated with occurrence of an exacerbation.…”

Section: Causes Of Exacerbationsmentioning

confidence: 97%

Relation between inflammation and symptoms in asthma

Tillie‐Leblond

Montani

Crestani

et al. 2009

Allergy

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Asthma symptoms are the main reason for healthcare utilization and are a fundamental parameter for the evaluation of asthma control. Currently, asthma is defined as a chronic inflammatory disease. A French expert group studied the association between inflammation and asthma symptoms by carrying out a critical review of the international literature. Uncontrolled asthmatics have an increased number of polynuclear eosinophils in the induced sputum and an increased production of exhaled NO. Control by anti‐inflammatory treatment is accompanied by a reduction in bronchial eosinophilia and exhaled NO. Asthma symptoms are the result of complex mechanisms and many factors modify their perception. Experimental data suggest that there is a relationship between the perception of symptoms and eosinophilic inflammation and that inhaled corticoid therapy improves this perception. Although they are still not applicable in routine practice, follow‐up strategies based on the evaluation of inflammation are thought to be more effective in reducing exacerbations than those usually recommended based on symptoms and sequential analysis of respiratory function. Inhaled corticosteroid therapy is the reference disease‐modifying therapy for persistent asthma. Recent studies demonstrated that adjustment of anti‐inflammatory treatment based on symptoms is an effective strategy to prevent exacerbations and reduce the total number of doses of inhaled corticosteroids.

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Section: Causes Of Exacerbationsmentioning

confidence: 97%

Relation between inflammation and symptoms in asthma

Tillie‐Leblond

Montani

Crestani

et al. 2009

Allergy

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“…Isotype control Abs were used as negative controls. Grading was performed as previously described (9). Differences in immunohistochemical staining was quantified (for Rb and Bcl-2) as previously described (24,25).…”

Section: Immunohistochemistry and Tunel Analysismentioning

confidence: 99%

“…Previously, we have shown that airway epithelial cells provide critical signals for epithelial-immune cell interaction resulting in airway inflammation and remodeling (9)(10)(11)(12). We hypothesized that cellular proliferation and cell death of airway epithelial cells may explain, at least in part, the structural remodeling changes noted in severe asthma.…”

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confidence: 99%

Epithelial Cell Proliferation Contributes to Airway Remodeling in Severe Asthma

Cohen

Xueping

Tarsi

et al. 2007

Am J Respir Crit Care Med

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219

161

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Rationale: Despite long-term therapy with corticosteroids, patients with severe asthma develop irreversible airway obstruction. Objectives: To evaluate if there are structural and functional differences in the airway epithelium in severe asthma associated with airway remodeling. Methods: In bronchial biopsies from 21 normal subjects, 11 subjects with chronic bronchitis, 9 subjects with mild asthma, and 31 subjects with severe asthma, we evaluated epithelial cell morphology: epithelial thickness, lamina reticularis (LR) thickness, and epithelial desquamation. Levels of retinoblastoma protein (Rb), Ki67, and Bcl-2 were measured, reflecting cellular proliferation and death. Terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL) was used to study cellular apoptosis. Measurements and Main Results: Airway epithelial and LR thickness was greater in subjects with severe asthma compared with those with mild asthma, normal subjects, and diseased control subjects (p ϭ 0.009 and 0.033, respectively). There was no significant difference in epithelial desquamation between groups. Active, hypophosphorylated Rb expression was decreased (p ϭ 0.002) and Ki67 was increased (p Ͻ 0.01) in the epithelium of subjects with severe asthma as compared with normal subjects, indicating increased cellular proliferation. Bcl-2 expression was decreased (p Ͻ 0.001), indicating decreased cell death suppression. There was a greater level of apoptotic activity in the airway biopsy in subjects with severe asthma as compared with the normal subjects using the TUNEL assay (p ϭ 0.002), suggesting increased cell death. Conclusions: In subjects with severe asthma, as compared with subjects with mild asthma, normal subjects, and diseased control subjects, we found novel evidence of increased cellular proliferation in the airway contributing to a thickened epithelium and LR. These changes may contribute to the progressive decline in lung function and airway remodeling in patients with severe asthma.

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“…There are short-and long-term measures of asthma control (12,13). Short-term measures include the assessment of measures of airway inflammation and composite measures of asthma control such as the Asthma Control Questionnaire (ACQ).…”

Section: Assessment Of Asthma Control and Questionnairesmentioning

confidence: 99%

Asthma control or severity: that is the question

Humbert

Holgate

Boulet

et al. 2007

Allergy

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In the first National Heart Lung and Blood Institute and Global Initiative for Asthma (GINA) guidelines, the level of symptoms and airflow limitation and its variability allowed asthma to be subdivided by severity into four subcategories (intermittent, mild persistent, moderate persistent, and severe persistent). It is important to recognize, however, that asthma severity involves both the severity of the underlying disease and its responsiveness to treatment. Thus, the first update of the GINA guidelines defined asthma severity depending on the clinical features already proposed as well as the current treatment of the patient. In addition, severity is not a fixed feature of asthma, but may change over months or years, whereas the classification by severity suggests a static feature. Moreover, using severity as an outcome measure has limited value in predicting what treatment will be required and what the response to that treatment might be. Because of these considerations, the classification of asthma severity is no longer recommended as the basis for treatment decisions, a periodic assessment of asthma control being more relevant and useful.

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Asthma Exacerbations after Glucocorticoid Withdrawal Reflects T Cell Recruitment to the Airway

Cited by 50 publications

References 58 publications

Relation between inflammation and symptoms in asthma

Relation between inflammation and symptoms in asthma

Epithelial Cell Proliferation Contributes to Airway Remodeling in Severe Asthma

Asthma control or severity: that is the question

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