Airway Mucosal Inflammation Even in Patients with Newly Diagnosed Asthma

Laitinen, Lauri A.; Laitinen, Annika; Haahtela, Tari

doi:10.1164/ajrccm/147.3.697

Cited by 493 publications

(265 citation statements)

References 27 publications

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“…The use of fibreoptic bronchoscopy has allowed bronchial biopsies and lavage fluid to be examined in less severe asthmatics and in normal subjects. These studies have shown that eosinophils and T lymphocytes in particular are increased in number and activation status in asthmatic airways compared to controls (Jeffery et al 1989, Azzawi et al 1990, Bradley et al1991, Laitinen et al 1993. Furthermore, several studies have correlated the number of activated T cells and eosinophils with abnormalities in FEV1 and airway reactivity (Walker et al 1991) and with clinical severity in asthma (Bousquet et al 1990).…”

Section: Asthma and Allergic Inflammationmentioning

confidence: 96%

IL-5 and IL-5 receptor in asthma

Kotsimbos

Hamid

1997

Mem. Inst. Oswaldo Cruz

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and a soluble isoform (αIL-5Rs). Cytokines such as IL-5 produce specific and non-specific cellular responses through specific cell membrane receptor mediated activation of intracellular signal transduction pathways which, to a large part, regulate gene expression. The major intracellular signal transduction mechanism is activation of non-receptor associated tyrosine kinases including JAK and MAP kinases which can then transduce signals via a novel family of transcriptional factors named signal transducers and activators of transcription (STATS). JAK2, STAT1 and STAT 5 appear to be particularly important in IL-5 mediated eosinophil responses. Asthma is characterized by episodic airways obstruction, increased bronchial responsiveness, and airway inflammation. Several studies have shown an association between the number of activated T cells and eosinophils in the airways and abnormalities in FEV1, airway reactivity and clinical severity in asthma. It has now been well documented that IL-5 is highly expressed in the bronchial mucosa of atopic and intrinsic asthmatics and that the increased IL-5 mRNA present in airway tissues is predominantly T cell derived. Immunocytochemical staining of bronchial biopsy sections has confirmed that IL-5 mRNA transcripts are translated into protein in asthmatic subjects. Furthermore, the number of activated CD 4 + T cells and IL-5 mRNA positive cells are increased in asthmatic airways following antigen challenge and studies that have examined IL-5 expression in asthmatic subjects before and after steroids have shown significantly decreased expression following oral corticosteroid treatment in steroid-sensitive asthma but not in steroid resistant and chronic severe steroid dependent asthma. The link between T cell derived IL-5 and eosinophil activation in asthmatic airways is further strengthened by the demonstration that there is an increased number of αIL-5R mRNA positive cells in the bronchial biopsies of atopic and non-atopic asthmatic subjects and that the eosinophil is the predominant site of this increased

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Section: Asthma and Allergic Inflammationmentioning

confidence: 96%

IL-5 and IL-5 receptor in asthma

Kotsimbos

Hamid

1997

Mem. Inst. Oswaldo Cruz

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“…with terbutaline for two years followed by 1,200 (8). This report provided evidence on which to base recommendations for treatment regarding the use of ICS in mild persistent asthma (9).…”

Section: P a T I E N T S Wi T H As T H Mamentioning

confidence: 99%

“…Chronic allergic airway inflammation is the major cause of the symptoms and bronchial hyperresponsiveness (BHR) in asthma, even in mild cases (1). Such inflammation may lead to changes in airway structure, causing irreversible airflow limitation and persistent symptoms (2,3)…”

Section: Introductionmentioning

confidence: 99%

Characteristics of Asthma Resistant to Moderate Dose Inhaled Corticosteroid Treatment on Bronchial Hyperresponsiveness

et al. 2006

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“…Their role in inflammatory processes has been inferred mainly from murine models and from their expression in human lesions, 4 but genetic epidemiology studies have also helped to document it. Accordingly, we postulated that chemokine polymorphisms that alter cell mobilization and activation may be associated with asthma risk and severity.…”

Section: Introductionmentioning

confidence: 99%

A polymorphism in the CCL2 chemokine gene is associated with asthma risk: a case–control and a family study in Tunisia

et al. 2008

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Asthma is a complex genetic disorder characterized by chronic airway inflammation. We hypothesized that genetic polymorphisms in chemokines and their receptors alter leukocyte mobilization and may thus influence the risk and severity of childhood asthma. Distributions of the chemokine CCL2-2578G, CCL2-927C, CCR2-V64I, CX3CR1-V249I and CX3CR1-T280M receptor polymorphisms were examined in a case-control study of 121 children with asthma and 226 age-matched healthy controls and then replicated in a family study of 99 simplex families (297 individuals). The case-control study revealed that the CCL2-2578G allele was less frequent in children with than in those without asthma (P ¼ 0.0012). No association with asthma was found for the CCL2-927, CCR2 or CX3CR1 polymorphisms. The finding in the family study that the CCL2-2578G allele was transmitted less often by heterozygous parents to their children with asthma (P ¼ 0.0016) confirms the association of CCL2-2578G with asthma risk. Biochemical studies indicated that plasma CCL2 concentrations were higher in both patients (P ¼ 0.0214) and controls (P ¼ 0.001) carrying the G allele than in subjects with other polymorphisms. Both case-control and family-based studies suggest a protective effect of allele CCL2-2578G in Tunisian asthmatic children.

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Airway Mucosal Inflammation Even in Patients with Newly Diagnosed Asthma

Cited by 493 publications

References 27 publications

IL-5 and IL-5 receptor in asthma

IL-5 and IL-5 receptor in asthma

Characteristics of Asthma Resistant to Moderate Dose Inhaled Corticosteroid Treatment on Bronchial Hyperresponsiveness

A polymorphism in the CCL2 chemokine gene is associated with asthma risk: a case–control and a family study in Tunisia

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