Disordered Airway Function Research Articles

Asthma History, Current Situation, an Overview of Its Control History, Challenges, and Ongoing Management Programs: An Updated Review.

Asthma is a disease of the airways that is characterized by chronic inflammation and disordered airway function. The purpose of writing the current review paper is to review the history, current situation, control history, challenges, and ongoing management programs of asthma. Some official websites of known respiratory professional bodies were consulted for asthma guidelines, and information from Google Scholar® and PubMed® was also consulted. We reviewed around two hundred eight papers, and then, inclusion and exclusion criteria were applied to prepare this manuscript. Out of these papers, thirty papers, factsheets, and some official websites were used to prepare this manuscript. Physicians should follow already existing asthma guidelines in order to manage asthma. All prescribed medications should be continued. The government should make and adopt more strategies to promote the rational use of anti-asthmatic drugs and healthcare facilities and also make plans to disseminate more awareness among people about the schemes and programs made for safeguarding people against this life-threatening disease. We have done so much advancement to fight against this deadly disease, and we still need time to make the globe asthma-free. The number of people suffering from asthma is more than the number of people suffering from HIV infection and tuberculosis. Understanding the recommendations of professional bodies will assist in medical decision-making in asthma management. The individual needs of patients should be considered by healthcare professionals.

A Brief History of Asthma and Its Mechanisms to Modern Concepts of Disease Pathogenesis

The original concept of asthma being primarily a disease of airways smooth muscle drove the development of bronchodilator drugs. However when it was realised that airway inflammation underpinned the disordered airway function, this gave way to the development of controller therapies such as inhaled cromones and corticosteroids. More recently the discovery of complex interconnecting cytokine and chemokine networks has stimulated the development of biologics with varying success. With the recognition that airway wall "remodelling" is present early in asthma inception and is in part driven by aberrant epithelial-mesenchymal communication both genetic and environmental factors beyond allergen exposure such as virus infection and air pollution are being seen as being increasingly important not only in asthma exacerbations but in the origins of asthma and its evolution into different sub-phenotypes. This brings us round full circle to once again considering that the origins of asthma lie in defects in the formed elements of the airway; the epithelium, smooth muscle, and vasculature. Over the last 25 years Professor You Young Kim has engaged in the exciting discovery science of allergy and asthma and has made an enormous contribution in bringing Korea to the forefront of disease management and research, a position that both he and his colleagues can justly be proud of.

Lessons learnt from the epidemic of asthma.

In his ‘Treatise on Asthma; Its Pathology and Treatment’ published in 1860, Henry Hyde Salter, a London physician, described the disorder as ‘ paroxysmal dyspnoea of a peculiar character, generally periodic with intervals of healthy respiration between the attacks’ .1 Although at that time the concept of allergy had not yet been introduced, Salter was aware of the hereditary nature of the disease, and its relation to ‘idiosyncrasies’ such as the emanations of horses, cats and other animals. Similarly, he appreciated the importance of emotional disturbances in asthma. However, it took a further 30 years before William Osler, in his first edition of Principles and Practices of Medicine (1892),2 connected disordered airway function of asthma with a variety of pathological changes in the lung, including bronchial mucosal oedema, inflammation and the production of ‘gelatinous’ mucus. Osler also drew attention to the bizarre and extraordinary variety of circumstances which, at times induced a paroxysm, including exposure to allergens, emotions, diet and the common cold (Table 1). It is this hyper-responsiveness of the airways to a variety of direct and indirect stimuli that is characteristic of asthma and differentiates it from other lung diseases. Bronchial hyper-responsiveness (BHR) can be quantified in the laboratory using incremental doses of a stimulus such as methacholine and histamine (direct stimuli) or allergen, adenosine, cold dry air or exercise (indirect stimuli that cause airway narrowing through the release of mediators from airway cells). By measuring the incremental fall in a measure of lung function such as the forced expiratory volume in 1 s (FEV1), the concentration dose response curve in asthma is steeper and displaced to the left, allowing quantification in the form of a provocative concentration or dose of agonist that reduces lung function by 20% of baseline (PC20). The lower the PC …

アレルギー疾患における遺伝因子の機能的解析とその臨床応用 ＩＬ‐１３を中心に

Allergic diseases are complex disorders involving a combination of genetic and environmental factors. In case of bronchial asthma, these factors result in infiltration of Th-2 lymphocytes, mast cells and eosinophils into asthmatic airways with downstream mediator release and disordered airway function. Cytokines derived from the Th-2 lymphocytes are considered to orchestrate the asthmatic phenotype. Among Th2 cytokines, the significance of IL-13 in the pathogenesis of bronchial asthma has recently emerged. Particularly, the direct action of IL-13 on bronchial epithelial cells is critical for generation of airway hyperresponsiveness. IL-13 signal is regulated by two receptors; one is the heterodimer composed of the IL-13 receptor α1 chain and the IL-4 receptor α chain which transduces IL-13 signal, and the other is the IL-13 receptor α2 chain which blocks the IL-13 signal. In this review article, we present our recent findings about the expression mechanism of the IL-13 receptors on bronchial epithelial cells and the functional role of a single nucleotide polymorphism on IL13 gene as a genetic factor. These findings give us a hint to improve the asthmatic condition by blocking the IL-13 actions.

Bronchial epithelium as a key regulator of airway allergen sensitization and remodeling in asthma.

Asthma is a chronic inflammatory disorder of the airways manifesting as intermittent airflow limitation, which over time may become progressive (1). Both in the allergic and nonallergic forms of the disease there is evidence of an altered local T cell response in favor of Th2 cytokine release resulting in B cell isotype switching to IgE; mast cell, eosinophil, and basophil recruitment; and activation and release of a wide range of inflammatory mediators (2). However, it has become clear that, by itself, inflammation is not able to explain many of the features characteristic of chronic asthma and that restructuring of the airway wall is also required (3). This “remodeling” response presumably accounts for the incomplete therapeutic efficacy of corticosteroids, with persistence of bronchial hyperresponsiveness (BHR), and the progressive decline in pulmonary function over time that occurs in those asthmatic individuals with more chronic and severe disease (1). Although atopy, the propensity to generate allergen-specific IgE, is one of the strongest risk factors for asthma, especially in children and young adults, only 10% of atopics develop chronic asthma and, as adults, asthma occurs in the absence of atopy, most notably in those with more severe and chronic disease. It seems plausible that, rather than IgE-mediated inflammation being the initiator of disordered airway function, the epithelium itself is abnormal and it is this that predisposes the individual with asthma toward local allergen sensitization, and the injurious effects of respiratory viruses and air pollutants (including tobacco smoke). A disordered epithelium could also provide a basis for airway remodeling in asthma.

Granulocyte-macrophage colony-stimulating factor, eosinophils and eosinophil cationic protein in subjects with and without mild, stable, atopic asthma

Increasing evidence implicates the eosinophil as an important effector cell in asthma, but little is known regarding its regulation in vivo. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to regulate eosinophil function in vitro. We investigated the in vivo role of eosinophils and GM-CSF in mild asthma. We compared the number and function of eosinophils and the presence of GM-CSF in blood, bronchoalveolar lavage (BAL) and biopsy tissue obtained from eight mild, stable, atopic asthmatics and 10 nonasthmatics, five of whom were atopic and five nonatopic. Eosinophils were significantly increased in the blood, BAL and biopsy tissue from asthmatics. Activated eosinophils, assessed by immunostaining for the secreted form of eosinophil cationic protein (EG2), were also increased in asthmatic BAL cells and biopsy tissue. Significant increases in GM-CSF in BAL cells and biopsy tissue from asthmatics were also evident. Significant positive correlations existed between GM-CSF in BAL and EG2, and GM-CSF in biopsy tissue and BAL and biopsy eosinophils. Airway responsiveness was also significantly positively correlated with eosinophil number and activation, and with GM-CSF. These results demonstrate that there are increased numbers of activated eosinophils and GM-CSF is increased in patients with mild asthma. Furthermore, GM-CSF is correlated with eosinophil number and function in vivo and these indices are significantly correlated with airway function. These findings emphasize the importance of eosinophils, potentially regulated in vivo by GM-CSF, in contributing to the disordered airway function evident even in mild asthma.

The Role of the Eosinophil in Asthma

After the initial description of the histochemical characteristics of the eosinophil by Paul Erhlich in 1879 (1), recognition that this cell has associations with asthma was soon appreciated. Some of the earlier histopathologic descriptions of bronchial tissue from patients who had died from asthma contain vivid descriptions of the heavy eosinophil infiltrate of the airway walls, and for many years clinicians have also recognized the presence of free eosinophils in the sputum of patients with asthma, particularly during acute exacerbations (2). The characteristic Charcot-Leyden crystals frequently observed in eosinophilenriched sputum represent a crystallized form of the enzyme lysolecithinase derived from degenerated eosinophils (3). Finally, the presence of increased numbers of eosinophils in the peripheral blood of patients with both atopic and nonatopic (intrinsic) asthma (4) provides further evidence implicating these cells in the pathogenesis of this form of disordered airway function.

Allergic Inflammation and Its Pharmacological Modulation in Asthma

While most asthma occurs in association with atopy, the relationship of this to clinical expression of the disease is not clearly understood. Allergen provocation causes an immediate bronchoconstriction (early asthmatic reaction) due to the release of mast-cell-derived histamine, prostaglandin D2 and leukotriene C4. The late reaction and attendent increase in bronchial responsiveness are associated with eosinophil influx, activation and mediator secretion, resulting in mucosal swelling in addition to smooth muscle contraction. Endobronchial biopsy and broncho-alveolar lavage have provided compelling evidence that both mast cells and eosinophils contribute to disordered airway function in 'clinical' asthma and that these cells are under the control of T lymphocytes. Topical corticosteroids which produce beneficial clinical effects probably do so by inhibiting those factors that maintain mast cell and eosinophil populations and their enhanced activation. The most likely contenders for these regulatory functions are the cytokines, particularly interleukin-3, -4 and -5.