Airway obstructive responses

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). 

The prevalence of airways obsfrucfion in this workforce was 3.3 times greater than expected when compared to national data. Nineteen of the 21 workers identified wifh airways obstruction had fixed airways obstruction. Cumulative worker exposures were calculated in parts per million diacetyl-years and workers were placed in equally sized worker categories of least, minimally, moderately, and most exposed. When successive categories of leasf fo greatest exposed workers were compared, it was found fhaf fhe proportion of workers with airways obstruction increased and average-percent-predicted FEVi decreased, demonstrating an exposure-response relationship with diacetyl. Five of... 

Three factors contribute to airway obstruction in asthma (1) contraction of the smooth muscle that surrounds the airways (2) excessive secretion of mucus and in some, secretion of thick, tenacious mucus that adheres to the walls of the airways and (3) edema of the respiratory mucosa. Spasm of the bronchial smooth muscle can occur rapidly in response to a provocative stimulus and likewise can be reversed rapidly by drug therapy. In contrast, respiratory mucus accumulation and edema formation are likely to require more time to develop and are only slowly reversible. 

Asthma is a chronic inflammatory condition characterized by bronchial hyper-responsiveness and reversible airway obstruction. Cytokine release from a variety of cell types such as eosinophils, lymphocytes and other inflammatory cells produces epithelial sloughing, plasma protein extravasation from the tracheobronchial microcirculation and airway remodeling. Bronchial mucosal inflammation is present in all patients. The primary goal of asthma management is to maintain control of the disease process by reducing symptoms and improving lung function. 

Since the introduction of propranolol, it has been recognized that patients with bronchial asthma treated with beta-adrenoceptor antagonists can develop severe airways obstruction (84), which can be fatal (85) or near fatal (86,87) this has even followed the use of eye-drops containing timolol (88). Beta-blockers upset the balance of bronchial smooth muscle tone by blocking the bronchial beta2-adrenoceptors responsible for bronchodilata-tion. They also promote degranulation of mast cells and depress central responsiveness to carbon dioxide (89,90). 

Topical anesthesia of the airways is commonly used to facilitate endoscopy and sometimes manipulation of the airways. This can result in an increase in airway flow resistance, possibly due to laryngeal dysfunction (21). Lidocaine spray 10%, used for upper airways anesthesia for fiberoptic intubation in a grossly obese patient, caused acute airway obstruction. The patient went on to have a percutaneous tracheotomy, and it was postulated that the local anesthetic had abolished laryngeal receptors responsible for airway maintenance, or that laryngospasm and reduced muscle tone due to the lidocaine might have been the cause (SEDA-22,140). 

In heaves-affected horses, fluticasone propionate (2000 pg twice daily by Equine AeroMask) has been shown to reduce pulmonary neutrophilia, improve parameters of pulmonary function and reduce responsiveness to histamine challenge during an episode of airway obstruction (Viel 1999). In normal horses, fluticasone propionate reduces serum cortisol concentrations by 40% after 1 day of therapy and by 65% after 7 days. Serum cortisol concentrations return to pretreatment values within 1-2 days after the discontinuation of drug treatment. 

Rafferty P, Beasley R, Holgate S T 1998 Comparison of the efficacy of preservative free ipratropium bromide and Atrovent nebuliser solution. Thorax 43 446-450 Robinson N, Derksen F, Berney C et al 1993 The ainway response of horses with recurrent airway obstruction (heaves) to aerosol administration of ipratropium bromide. Equine Veterinary Journal 25 299-303 Robinson N, Derksen F, Olszewski M 1996 The... 

Following alleigen challengp, up to 50% of asthmatic subjects exhibit a dual bronchoconstrictor response. There is a rapid tall in pulmonary function (e.g FEVi) at 10-20 min which gradually recovers over the Following 2 h, defined as the EAR. Between 4 and 6 h there is a further fiill in FEVi, the LAR. This may last up to 12 h and in some individuals may be followed by recurring airway obstruction for several days or even weeks (Booij Noord ad., 1972). 

One of the most striking pathological features of chronic asthma is an increase in the smooth muscle mass of the airways (DunniU etal., 1969 Heard and Hossain, 1973 Hossain, 1973 Ebina etal., 1990). Hyperplasia (increase in cell number) rather than hypertrophy (increase in cell size) predominantly produces this increase in mass, and the associated reduction in airway luminal diameter. This fixed increase in muscle mass contributes to the component of airways obstruction observed in chronic asthmatics which is irreversible with bronchodilators. It also leads to an exaggerated response to bronchoconstrictor stimuli, equivalent to the characteristic bronchial hyperresponsiveness of asthmatics (James et al., 1989 Pare et al., 1991 Pare, 1993). 

Asthma is a disease characterized by reversible airways obstruction and increased responsiveness of the airways to specific and nonspecific bronchocon-strictor stimuli. Indeed, the latter feature may be used in diagnosis of asthma (vide infra). Obstruction to the flow of air in asthma is the product of three factors smooth muscle contraction, mucosal edema, and augmented mucus secretion. Pathological features, such as infiltration of the airway walls with inflammatory cells (e.g., eosinophils, neutrophils), and the efficacy of antiinflammatory steroids in treating the disease have pointed to an important role of inflammation in the disease process. 

Episodes of airway obstruction or bronchoconstriction may be induced in asthmatics by exposure to stimuli to which they are sensitized, such as inhalation of a specific pollen or house dust mite, or exposure to an occupational stimulus, e.g., red cedar dust [47]. Binding of antigen (e.g., pollen) to specific receptors (antibodies) on the surface of an inflammatory cell (e.g., mast cell) results in the elaboration of prestored mediators, such as histamine, and in the synthesis of newly formed mediators, such as arachidonic acid metabolites (e.g., prostaglandins and leukotrienes). Cellular sources of the various mediators are shown in Table 3. Cytokines and chemokines are proteins that participate in pulmonary immune and inflammatory responses. While important, these have not been subjected to discussion in this chapter because these fields are changing very... 

In patients with chronic airways obstruction salmefamol (5) gave greater response than 4, particularly 6 to 8 hr. post dose.24<2 Orally (2 mg) 5 caused a fall in diastolic blood pressure, whereas 1 mg dose did not, and both were found equally effective on ventilatory capacity.2 By inhalation fenoterol (6) was equipotent with 4 in the treatment of asthmatic children but caused some increases in pulse rate.2 Orally, 6. caused significant bronchodilatation with rapid onset (30 min.) and long duration (6 hrs.) but showed mild tremors and increased pulse rates at higher doses (15, 20 mg).28 Carbuterol (7) (SKF 40383) in a double-blind study produced safe and effective bronchodilatation both orally (4 mg) and by inhalation28 (300 jug), but was less potent than 4. ... 

Reversible airway obstruction is common in asthma and chronic obstructive pulmonary disease (COPD). An increase in FEVi after an inhaled/f-agonist of 12% and greater than 0.2 L suggests an acute bronchodilator response. 

Viral infections are primarily responsible for exacerbations of asthma. Viral upper respiratory tract infections are a major precipitant of acute asthma in children, being involved in up to 20% to 40% of acute episodes. Infants are particularly susceptible to airways obstruction and wheezing with viral infections because of their small airways. The most common cause of exacerbations in both children and adults is the common rhinovirus." Other viruses isolated include respiratory syncytial virus (RSV), parainfluenza virus, coronavirus, and influenza viruses. The inflammatory response to viral infection is thought to be associated directly with the increasing BHR. Certain viruses (RSV and parainfluenza virus) are capable of inducing spe-... 

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