Relative effects of inhaled corticosteroids on immunopathology and physiology in asthma: a controlled study.

Burke, Conor M.; Sreenan, Séamus; Pathmakanthan, Shri; Patterson, J.; Schmekel, Birgitta; Poulter, L W

doi:10.1136/thx.51.10.993

Cited by 32 publications

(19 citation statements)

References 28 publications

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“…Lymphocytes, similar to eosinophils and neutrophils, are typically not present in the healthy lung. While granulocytes tend to arrive early in the inflammatory timeline, lymphocytes typically arrive many hours to days after the initial insult and orchestrate the antigen specific response (21, 22). These cells are attracted by a number of mediators and themselves produce a complex array of Th1, Th2 and other cytokines and chemokines.…”

Section: Resultsmentioning

confidence: 99%

A2B Adenosine Receptor Expression by Myeloid Cells Is Proinflammatory in Murine Allergic-Airway Inflammation

Belikoff

Vaickus

Sitkovsky

et al. 2012

The Journal of Immunology

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Asthma is a chronic condition with high morbidity and healthcare costs, and cockroach allergens are an established cause of urban pediatric asthma. A better understanding of cell types involved in promoting lung inflammation could provide new targets for the treatment of chronic pulmonary disease. Due to its role in regulating myeloid cell dependent inflammatory processes, we examined A2B R expression by myeloid cells in a cockroach allergen (CRA) model of murine asthma-like pulmonary inflammation. Both systemic and myeloid tissue-specific A2B R deletion significantly decreased pulmonary inflammatory cell recruitment, airway mucin production, and pro-inflammatory cytokine secretion after final allergen challenge in sensitized mice. A2B R deficiency resulted in a dramatic reduction on Th2 type airways responses with decreased pulmonary eosinophilia without augmenting neutrophilia, and decreased lung IL-4, IL-5, and IL-13 production. Chemokine analysis demonstrated that eotaxin 1 and 2 secretion in response to repeated allergen challenge is myeloid cell A2B R dependent. In contrast, there were no differences in the levels of the CXC chemokines KC and MIP-2 in the myeloid cell A2B R deficient mice strengthening A2B R involvement in the development of Th2 type airways inflammation. Pro-inflammatory TNF-α, IFN-γ and IL-17 secretion were also reduced in systemic and myeloid tissue-specific A2B R deletion mouse lines. Our results demonstrate Th2 type predominance for A2B R expression by myeloid cells as a mechanism of developing asthma-like pulmonary inflammation.

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Section: Resultsmentioning

confidence: 99%

A2B Adenosine Receptor Expression by Myeloid Cells Is Proinflammatory in Murine Allergic-Airway Inflammation

Belikoff

Vaickus

Sitkovsky

et al. 2012

The Journal of Immunology

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“…These treatments have been shown to effectively control airway inflammation and bronchoconstriction, respectively (2,4,7,9,13,14). Recently, combination therapy, i.e., the addition of a long-acting ␤ 2 -agonist to low-to-medium doses of inhaled corticosteroids, has become the preferred treatment for moderate persistent and severe asthma in adults and children.…”

Section: Discussionmentioning

confidence: 99%

Combined budesonide/formoterol therapy in conjunction with allergen avoidance ameliorates house dust mite-induced airway remodeling and dysfunction

Johnson

Pacitto²,

Wong³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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5, 2008; doi:10.1152/ajplung.90229.2008.-Allergic asthma is characterized by airway inflammation in response to chronic allergen exposure, resulting in remodeling of the airway wall accompanied by dysfunctional airway physiology. However, a link between the immune-inflammatory response to allergen and changes to airway structure and physiology has not yet been fully elucidated. Moreover, the impact of inhaled corticosteroids and ␤2-agonists, the primary pharmacotherapy for asthma, on this process has not been completely evaluated. In this study, we employed a murine model of chronic exposure to a common environmental aeroallergen, house dust mite, to recapitulate the phenotype of clinical asthma. By examining the therapeutic effects of corticosteroid/␤ 2-agonist combination therapy with budesonide/formoterol (BUD/FORM) in this model of airway disease, we endeavored to determine the impact of BUD/FORM on lung inflammation, structure, and physiology. BUD/FORM was delivered either while allergen exposure was ongoing (concurrent therapy) or following the cessation of allergen exposure (postexposure therapy). Our results show that airway inflammation was substantially reduced in BUD/FORM-treated mice in the concurrent therapy group, whereas in the postexposure therapy group airway inflammation spontaneously resolved. In contrast, BUD/FORM was most effective in resolving several aspects of airway remodeling and bronchial hyperreactivity when delivered in conjunction with allergen withdrawal. This study demonstrates that although both BUD/FORM therapy and allergen avoidance independently reduce airway inflammation, only BUD/FORM therapy in conjunction with allergen avoidance can effectively reverse airway remodeling and bronchial hyperreactivity induced by chronic allergen exposure.

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“…Fibreoptic bronchoscopy was performed 1 week before (baseline) and 4–5 hours after the allergen challenge had commenced, as described in detail elsewhere 10. At least three endobronchial biopsy samples were obtained at each time point through the bronchoscope with sterile cup and spike forceps from the second generation right upper lobe bronchus.…”

Section: Methodsmentioning

confidence: 99%

Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge

Jahnsen

Moloney²,

Hogan³

et al. 2001

Thorax

186

139

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Background-Airway dendritic cells (DC)play an important role in chronic allergic airway inflammation in experimental animals, but a similar role for DC in human allergic asthma has been diYcult to define. This pilot study was undertaken to elucidate the role of DC in allergic asthma by examining their potential to migrate to the lower airways in response to bronchial challenge with specific allergen. Methods-Bronchial biopsy specimens were obtained from seven patients with allergic asthma before and 4-5 hours after allergen challenge. Multicolour immunofluorescence staining was performed on mucosal cryosections to identify changes in the number and phenotypes of DC. Results-A dramatic increase in the number of CD1c+HLA-DR+ DC were observed in the lamina propria after challenge compared with baseline (22.4 v 7.8 cells/mm 2 ). The rapid accumulation (within 4-5 hours) of these cells strongly suggests that they were directly recruited from peripheral blood. Conclusion-We have shown for the first time that a specific DC subset rapidly emigrates into the human bronchial mucosa during allergic inflammation. While this study is based on relatively few patients, the consistency of the overall results strongly suggests that the rapid population dynamics of human airway DC closely parallel those in animal models of acute inflammation. These findings support suggestions that DC have an important role in human airway allergy. (Thorax 2001;56:823-826)

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Relative effects of inhaled corticosteroids on immunopathology and physiology in asthma: a controlled study.

Cited by 32 publications

References 28 publications

A2B Adenosine Receptor Expression by Myeloid Cells Is Proinflammatory in Murine Allergic-Airway Inflammation

A2B Adenosine Receptor Expression by Myeloid Cells Is Proinflammatory in Murine Allergic-Airway Inflammation

Combined budesonide/formoterol therapy in conjunction with allergen avoidance ameliorates house dust mite-induced airway remodeling and dysfunction

Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge

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