New Insights into Asthma Pathogenesis

The −675 4G/5G plasminogen activator inhibitor‐1 promoter polymorphism in house dust mite‐sensitive allergic asthma patients

“…Asthma is a heterogenous disease and both bronchial reactivity and tsIgE levels can be influenced by genetic and environmental factors. Moreover, lung function test results, bronchial reactivity and tsIgE levels change with time as disease progresses and are also influenced by medications (16, 17, 20). Our approach to study a subpopulation of HDM‐AAs was selected because sensitization to HDM is an independent risk factor for asthma, is prevalent in allergic asthmatics and allows selection of HDM‐AAs early in the course of the disease (21, 22).…”

“…The strongest association was observed between the −675 4G/5G polymorphism and nonspecific bronchial reactivity suggesting that the effect of PAI‐1 on bronchial reactivity may be the predominant effect in asthma. It has been demonstrated that airway inflammation and remodeling of the bronchial wall are major factors leading to bronchial hyperreactivity (3, 20). Resolving the role of PAI‐1 in these two processes may therefore, help to understand a possible mechanism in which this protease inhibitor may affect bronchial responsiveness and development of asthma.…”

Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms

“…4) Localisation of Th2 inflammation being favoured by the EMTU enabling Th2 cytokines, such as granulocyte-macrophage colony-stimulating factor, and IL-4, -9 and -13, to work in concert to maintain inflammation and drive remodelling ''responses'' ( fig. 1) [5,52].…”

“…While recent asthma guidelines emphasise the importance of treating the underlying inflammatory response of asthma [3,4], it is disappointing that beyond corticosteroids and b 2 -adrenoceptor agonists, there has been little new to add to the therapeutic armamentarium (table 1). An important reason for this is that the underlying paradigm for the cellular and mediator pathways that are thought to be involved in asthma fall short of those responsible for its underlying cause [5]. Rather, they are more directed towards the mechanisms of atopy and underlying allergy and not to why the atopic phenotype expresses itself in the lower airways and persists there in association with structural changes.…”

Developmental origins of asthma and related allergic disorders

“…While there are two basic components which contribute to airflow limitation in asthma, namely airway inflammation and altered airway wall structure, most studies of the environmental influences on the disease have concentrated on allergic sensitisation. It has now become clear that concentrating on the cellular and mediator pathways producing an allergic inflammatory response falls short of explaining the full pathology of the disease (Holgate et al 2004). Hitherto it has been assumed that allergic inflammation is the main cause of the structural changes and that one follows the other.…”