Airways asthma

Preexisting airway damage (such as that caused by prior toxic inhalant exposure) may seriously compromise the respiratory system s normal protection and clearance mechanisms. Specifically, there may be depletion of critical enzyme systems. Cigarette smoking may severely compromise airway function with respect to both airway patency and clearance mechanisms. Hyperreactive airways (asthma in varying degrees) are seen in up to 15% of the adult population. Toxic inhalant exposures... 

This chapter discusses the role of chemokines and their receptors in inflammatory diseases of the airways (asthma and COPD), the intestinal tract (inflammatory bowel diseases), the joints (arthritis), the blood vessels (arteriosclerosis), the central nervous system (multiple sclerosis) and the skin (psoriasis). Investigations of receptor-mediated and intracellular signal pathways in chemokine—receptor interactions... 

Asthma is an extremely complex condition characterized by variable and reversible airways obstmction combiaed with nonspecific bronchial hypersensitivity (1 3). The cause of asthma, which is not always readily diagnosed (4), remains unknown. Days, if not weeks, ate needed to document the spontaneous reversal of the airways obstmction ia some patients. Asthmatics experience both an immediate hypersensitivity response and a delayed late-phase reaction, each mediated by a different pathway. Chronic asthma has come to be viewed as an inflammatory disease (5). The late-phase reaction plays a key role ia iaduciag and maintaining the inflammatory state which ia turn is thought to iaduce the bronchial hyperresponsiveness (6). The airways obstmction results from both contraction of airways smooth muscle and excessive bronchial edema. Edema, a characteristic of inflammatory states, is accompanied, ia this case, by the formation of a viscous mucus which can completely block the small airways. 

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... 

ASTHMA Periodic attacks of wheezing, chest tightness and breatlilessness resulting from constriction of the airways. 

Forced vital capacity (FVC) quantifies the maximum air volume expired following a maximal inspiration and is one of the basic measures of analyzing flow changes such as reduced airway patency observed in asthma. To measure FVC, an individual inhales maximally and then exhales as rapidly and completely as possible. FVC primarily reflects the elastic properties of the respiratory tract. The gas volume forcibly expired within a given time interval, FEV (where t is typically one second, FEVj q)... 

Many irritative chemicals may cause non-specific hyper-responsitivity of the airways and skin. The number of irritating chemicals is very large, several thousands. The symptoms caused by exposure to irritants may resemble allergic symptoms. In addition, exposure to irritating substances (such as sulfur dioxide or solvent vapors) often triggers the symptoms in individuals with allergic asthma. 

According to the Global Initiative for Asthma (GINA, http //www.ginasthma.org), asthma affects about 300 million people worldwide. Men of all ages are affected by this chronic airway disorder that, without appropriate treatment, limits quality of life and is sometimes fatal. 

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. 

Bronchial Asthma. Figure 2 Mechanisms of bronchial hyperresponsiveness. Toxic products from eosinophils [cationic peptides, reactive oxygen species (ROS)] cause epithelial injury. Nerve endings become easily accessible to mediators from mast cells, eosinophils [eosinophil-derived neurotoxin (EDN)], and neutrophils, and to airborne toxicants such as S02. Activation of nerve endings stimulates effector cells like mucosal glands and airway smooth muscle either directly or by cholinergic reflexes. 

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. 

W ithin the past few years a number of new drugs have been introduced to treat respiratory disorders, such as bronchial asthma and disorders that produce chronic airway obstruction. This chapter discusses the bronchodilators, dragp that have been around for a long time but are still effective in specific instances, and the newer antiasthma drugs that have proven to be highly effective in the prophylaxis (prevention) of breathing difficulty. 

Asthma is a reversible obstructive disease of the lower airway. With asthma there is increasing airway obstruction caused by bronchospasm and bronchoconstriction, inflammation and edema of the lining of the bronchioles, and the production of thick mucus that can plug the airway (see Pig. 37-1). There are three types of asthma ... 

Sympathomimetics (drugs that mimic the sympathetic nervous system) are used primarily to treat reversible airway obstruction caused by bronchospasm associated with acute and chronic bronchial asthma, exercise-induced bronchospasm, bronchitis, emphysema, bronchiectasis (abnormal condition of the bronchial tree), or other obstructive pulmonary diseases. 

Corticosteroids, such as beclomethasone (Beclovent), flu-nisolide (AeroBid), and triamcinolone (Azmacort), are given by inhalation and act to decrease the inflammatory process in the airways of the patient with asthma, hi addition, the corticosteroids increase the sensitivity of the p2-receptors. With increased sensitivity of the ( -receptors, the p2-receptor agonist drugs are more effective... 

Asthma is a complex respiratory disorder that involves mast cell degranulation, mucous secretions, and smooth muscle hypertrophy and hyperresponsiveness. Smooth muscle hyperresponsiveness has suggested some defect in the regulation of smooth muscle contractility. Therefore, a number of studies concerning asthma have centered on whether alterations in the regulation of smooth muscle contraction (Figure 4) are responsible for hyperactivity in asthmatic airway smooth muscle. 

AS, Chung KF, Sturton G, Wong SIT, McKenzie AN Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. J Allergy Clin Immunol 2007 120 1324-1331. 

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