Inflammation airway

Theophylline s predominant mode of action appears to be bronchocHlation. However, it has also been shown that prophylactic acHriinistration of theophylline provides some protection from asthma attacks and suppresses the late-phase response (67,68). Some researchers beHeve that at therapeutic semm concentrations theophylline may inhibit the development of airway inflammation (69). There are conflicting reports on the effect of theophylline on allergen-induced bronchial hyperresponsiveness some clinical stucHes report a reduction in hyper-responsiveness, others do not (69,70). Theophylline clearly does not reverse the general bronchial hyperresponsiveness over the course of long-term therapy (71). Because of the relationship between... 

The activation of mast cells by allergen initiates the asthma symptoms within minutes after allergen contact, the early allergic response (EAR), within horns the late allergic response (LAR), and within years and after rqDeated asthma episodes, chronic airway inflammation, airway remodeling, and airway hyperresponsiveness. 

Airway inflammation is a characteristic clinical feature of asthma. The distinction between the LAR and chronic inflammation becomes more difficult as the disease progresses. Infiltrated leukocytes release ototoxic mediators such as reactive oxygen species (ROS) and cationic (basic) proteins causing epithelial damage and cyfo/cmas that perpetuate the inflammation. Sustained inflammation leads to airway hyperrespon-siveness and airway remodeling. 

Glucocorticoids are widely used to treat a variety of inflammatory and immune diseases. With the recognition that airway inflammation is present even in patients with mild asthma, treatment with glucocorticoids is now the mainstay of asthma therapy. Consequently, by far the most common use of glucocorticoids today is in the treatment of asthma and inhaled glucocorticoids have now become established as first-line treatment in adults and children with persistent asthma, the commonest chronic airway inflammatory disease. 

Inhaled NO has been used for treatment of persistent pulmonary hypertension of newborn infants, critical respiratory failure of preterm infants, and acute hypertension of adult cardiac surgery patients. PDE-5 inhibitors such as sildenafil are also effective for treatment of pulmonary hypertension. The combination of PDE-5 and NO inhalation yields additive beneficial effects on pulmonary hemodynamics. On the other hand, measurement of exhaled NO is a noninvasive and reproducible test that is a surrogate measure of airway inflammation in patients with bronchial asthma. 

SM, Wetsel RA, Yao Z, Martin R, Hamzeh N, Adelagun R, Amar S, Kheradmand F, Corry DB A new mechanism regulating the initiation of allergic airway inflammation. J Allergy Chn Immunol 2007 29 120 334-342. 

Gon Y Toll-like receptors and airway inflammation. Allergol Int 2008 57 33-37. 

Wells JW Cowled CJ, Giorgini A. Kemeny DM. Noble A Regulation of allergic airway inflammation by class I-restricted allergen presentation and CD8 T-cell infiltration. J Allergy Clin Immunol 2007 119 226-234. 

Sergejeva S, Ivanov S, Lotvall J, Linden A Interleukin-17 as a recruitment and survival factor for airway macrophages in allergic airway inflammation. Am J Respir Cell Mol Biol 2005 33 248-253. 96 Bush KA, Farmer KM, Walker JS, Kirkham BW Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgGl Fc fusion protein. Arthritis Rheum 2002 46 802-805. 

Miyahara N, Balhorn A, Dakhama A, Gelfand EW 126 IL-lO-treated dendritic cells decrease airway hyperresponsiveness and airway inflammation in mice. J Allergy Clin Immunol 2007 119 1241-1250. 

Polosa R, Holgate ST Adenosine receptors as promising therapeutic targets for drug development in chronic airway inflammation. Curr Drug Targets... 

Ray A, Cohn L (1999) Th2 cells and GATA-3 in asthma new insights into the regulation of airway inflammation. J Clin Invest 104(8) 985-993... 

Barnes, P.J. (1990). Reactive oxygen species and airway inflammation. Free Rad. Biol. Med. 9, 235-243. 

H. A. (1986). Ozone-induced change in bronchial reactivity to methacholine and airway inflammation in humans. J. Appl. Physiol. 60, 1321-1325. 

In the late phase response, activated airway cells release inflammatory cytokines and chemokines, recruiting inflammatory cells into the lungs. The late phase response occurs 4 to 6 hours after the initial allergen challenge and results in a less intense bronchoconstriction as well as increased airway hyperresponsiveness and airway inflammation.6... 

Airway hyperresponsiveness is defined as the exaggerated ability of the airways to narrow in response to a variety of stimuli. Although AHR exists in patients without asthma, it is a characteristic feature of asthma and appears to be directly related to airway inflammation and the severity of asthma.1,3 Treatment of airway inflammation with inhaled corticosteroids attenuates AHR in asthma but does not eliminate it.1 Clinically, AHR manifests as increased variability of airway function. Although not commonly used to diagnose asthma, AHR can be evaluated clinically using a methacholine or histamine bronchoprovocation test. 

Corticosteroids are the most potent anti-inflammatory agents available for the treatment of asthma. The efficacy of corticosteroids is due to their ability to affect multiple inflammatory pathways, resulting in the suppression of inflammatory cell activation and function, prevention of microvascular leakage, decreased mucus production, and upregulation of P2-adrenergic receptors.10,18 Clinically, corticosteroids decrease airway inflammation, decrease AHR, decrease mucus production and secretion, and improve the response to P2-agonists.18 Corticosteroids for the treatment of asthma are available in inhaled, oral, and injectable dosage forms. 

Inhaled corticosteroids are not equivalent on a milligram basis however, equivalent doses have been approximated (Table 11-3). Low to moderate doses have been shown to be safe and effective in all age groups. Although some effect is seen from inhaled corticosteroids within 12 hours, 2 weeks of therapy is necessary to see significant clinical effects, and longer treatment periods maybe necessary to see the full effect of these agents on airway inflammation and remodeling. 

Conroy DM, Jopling LA, Lloyd CM, et al. CCR4 blockade does not inhibit allergic airways inflammation. J Leukoc Biol 2003 74(4) 558-563. 

Kawasaki S, Takizawa H, Yoneyama H, et al. Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice. J Immunol 2001 166(3) 2055-... 

Humbles AA, Lu B, Friend DS, et al. The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. Proc Natl Acad Sci U S A 2002 99(3) 1479-1484. 

Lukacs NW, Standiford TJ, Chensue SW, Kunkel RG, Stricter RM, Kunkel SL. C-C chemokine-induced eosinophil chemotaxis during allergic airway inflammation. J Leukoc Biol 1996 60(5) 573-578. 

John AE, Berlin AA, Lukacs NW. Respiratory syncytial virus-induced CCL5/ RANTES contributes to exacerbation of allergic airway inflammation. Eur J Immunol 2003 33(6) 1677-1685. 

Chvatchko Y, Proudfoot AE, Buser R, et al. Inhibition of airway inflammation by amino-terminally modified RANTES/CC chemokine ligand 5 analogues is not mediated through CCR3. J Immunol 2003 171(10) 5498-5506. 

Corbel M, Belleguic C, Boichot E, Lagente V. Involvement of gelatinases (MMP-2 and MMP-9) in the development of airway inflammation and pulmonary fibrosis. Cell Biol Toxicol 2002 18(1) 51-61. 

Bronchial asthma is defined as a chronic inflammatory disease of the lungs it affects an estimated 9 to 12 million individuals in the U.S. Furthermore, its prevalence has been increasing in recent years. Asthma is characterized by reversible airway obstruction (in particular, bronchospasm), airway inflammation, and increased airway responsiveness to a variety of bronchoactive stimuli. Many factors may induce an asthmatic attack, including allergens respiratory infections hyperventilation cold air exercise various drugs and chemicals emotional upset and airborne pollutants (smog, cigarette smoke). 

Lukacs, N.W., Stricter, R.M., Chensue, S.W., Widmer, M. and Kunkel, S.L. (1995) TNF-alpha mediates recruitment of neutrophils and eosinophils during airway inflammation. Journal of Immunology 154, 5411-5417. 

Asthma is characterized by variable symptoms such as wheeze, shortness of breath and coughing and is usually associated with airway inflammation, with variably reduced spirometric indices [4, 5], with increased non-specific airway responsiveness (AR) to spasmogens [6, 7] and increased levels of semm immunoglobulin E (IgE) and eosinophils [8-10]. The symptoms of asthma are primarily due to excessive airway narrowing, which leads to an increased resistance to airflow, especially during forced expiration, and produces characteristic spirometric findings. A cardinal feature of asthma is that airway narrowing is reversible either spontaneously or as the result of therapy. 

At the cellular level, eosinophils, mast cells, alveolar macrophages, lymphocytes and neutrophils recruited to the airways of asthmatics produce a variety of inflammatory mediators, such as histamine, kinins, neuropeptides, and leukotrienes, which lead to airway smooth muscle constriction and obstruction of airflow, and the perpetuation of airway inflammation [20, 21]. An understanding of the inflammatory processes and the molecular pathways of these mediators has led to the development and widespread use of several pharmacologic agents that mitigate airway inflammation and bronchoconstriction. 

Howarth PH, Beckett P, Dahl R. The effect of long-acting beta2-agonists on airway inflammation in asthmatic patients. Respir Med 2000 94 (Suppl F) 22-25. 

Blake KV. Drug treatment of airway inflammation in asthma. Pharmacotherapy 2001 21 3S-20S. 

The latest studies show that reactive nitrogen species play even more important role in asthma development. It was found that exhaled nitrogen oxide, an indicator of eosinophilic airway inflammation, is drastically enhanced in asthmatic patients. Correspondingly, it has been shown that lung damage is characterized by the augmentation of nitrotyrosine and iNOS expression in neutrophils, eosinophils, and macrophages in the airways of asthmatic patients [266],... 

The major characteristics of asthma include a variable degree of airflow obstruction (related to bronchospasm, edema, and hypersecretion), BHR, and airway inflammation. 

Neutrophils are also a source of mediators (PAFs, prostaglandins, thromboxanes, and leukotrienes) that contribute to BHR and airway inflammation. 

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