Airway obstruction in asthma

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. 

In the first definitive monograph on asthma, published in 1864, Sir Henry Hyde Salter concluded that the airway obstruction in asthma results from bronchoconstriction, mucus plu ng of the airway lumen, and edema of the airway wall (Salter, 1864). Salter s interpretations were probably based on clinical observations rather than on pathological examinations, because post-mortem findings were not described at that time. In fact, the initial histopathological studies of the airways of asthmatics did not recognize the presence of mucosal edema For example, in the first description of a post-mortem examination of a patient who died in status asthmaticus, Leyden concluded that the airflow obstruction resulted from mucus in the airways and that the walls [of bronchi]. ..are not essentially changed (Leyden, 1886). 

Secretion Therapy. Airways obstruction in asthma is almost always partially due to often clinically unsuspected excessive secretions and mucus plugs. The therapeutic regimen described to this point may decrease this problem. Unfortunately, the treatment of the asthmatic s secretions is often neglected. 

Bronchial asthma is characterized by an increased responsiveness of the trachea and bronchi to various stimuli and is manifested by a widespread narrowing of the airways that changes in severity either spontaneously or as a result of therapy (91). Chronic bronchitis is defined as a condition with chronic or recurrent bronchial hypersecretion, cough and expectoration during at least 3 months for at least 2 successive years (92). Chronic bronchitis is often associated with chronic airways obstruction with minimal reversibility it is then called chronic obstructive pulmonary disease (COPD). Chronic airways obstruction in COPD is believed to be caused by either emphysema or irreversible obstructive changes in the peripheral airways, or both. There is an overlap between asthma and COPD, and many patients may have features of both diseases (93). Asthma is considered an important risk factor for the development of COPD. Bronchial hyperresponsiveness is a hallmark of asthma, whereas its importance in COPD is more obscure. Airway inflammation is a key factor for the development of bronchial hyperresponsiveness (94). Table 4 shows the main pathophysiological features of airways obstruction in asthma, chronic bronchitis, and emphysema. 

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). 

An inhalable medication that relaxes the muscles in the airways (bron-chodilator) is frequently administered when airways obstruction is identified. In this bronchodilator trial test, the spirometry test is subsequently repeated and compared to the results from the initial spirometry test. If there is substantial improvement in lung function with the administration of the bronchodilator, the airways obstruction is reversible. An example of a lung disease with reversible airways obstruction is asthma, in which s)nnptoms occur episodically when airways obstruction occurs. If there is little or no improvement after the administration of the bronchodilator, the airways obstruction is fixed. An example of a limg disease with fixed airways obstruction is BO, where there is scarring of the airways. 

Airflow obstruction in asthma is due to bronchoconstriction resulting from contraction of bronchial smooth muscle, inflammation of the bronchial wall, and increased mucous secretion. Asthmatic attacks may be related to recent exposure to allergens, inhaled irritants leading to bronchial hyperactivity and inflammation of the airway mucosa. The symptoms of asthma may be effectively treated by several drugs, but none of the agents provide a cure for this obstructive lung disease. 

Jackson SH, Beevers DG. Comparison of the effects of single doses of atenolol and labetalol on airways obstruction in patients with hypertension and asthma. Br J Clin Pharmacol 1983 15(5) 553-6. 

Asthma is a respiratory illness characterized by variable and reversible airflow obstruction. Over 100 years ago. Osier, in his influential Textbook of Medicine (Osier, 1892), concluded that airway wall edema, bronchoconstriaion and mucus plugging are responsible for the airflow obstruction in asthma. Since that time, edema of the airway mucosa has been assumed to be one of the central features of asthma, but comparatively few studies have addressed the issue directly. Therefore, there is litde information about the onset, duration, magnitude, location, mechanism, consequences and management of mucosal edema in asthma. 

Observations of relief of bronchoconstriction without cardiovascular side effects suggest that prostaglandins have a potential clinical role in conditions such as asthma. Cuthbert [273] compared the effect of aerosol-administered PGEi on airways resistance in healthy and asthmatic volunteers with reversible airways obstruction. In the healthy subjects, the forced expiratory volume in one second (FEVi) was unaffected by the prostaglandin when administered as the free acid or as the triethanolamine salt. However, in the asthmatics, inhalation of 55 pg of the triethanolamine salt produced an increase in FEVi comparable in both degree and duration with that produced by an inhalation of 550 jig of isoprenaline sulphate. The triethanolamine salt was employed in the asthmatic trials since it was better tolerated, the free acid being irritant to the upper respiratory tract. Similar results were obtained with PGE2 [274]. 

Backman KS, PA Greenberger, R Patterson. 1997. Airways obstruction in patients with long-term asthma consistent with irreversible asthma . Chest 112 1234. 

Kuwano K, Bosken CH, Pare PD, Bai TR, Wiggs BR, Hogg JC. Small airways dimensions in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1993 148 1220-1225. 

Airway inflammation, and probably its effects on airway structure (airway remodeling), are considered to be responsible not only for the acute but also the longterm changes in airway function in asthma such as persistent airway responsiveness and variable airflow obstruction (56-59). 

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. 

An MRL of 0.07 ppm has been derived for acute-duration inhalation exposure to hydrogen sulfide. This MRL is based on a LOAEL of 2 ppm for respiratory effects—bronchial obstruction (30% change in airway resistance) in 2/10 persons with asthma reported in the Jappinen et al. 1990 study (Table 2-1 LSE 16). An uncertainty factor of 30 was applied,... 

Based on a LOAEL of 2 ppm for respiratory effects—bronchial obstruction (30% change in airway resistance) in 2/10 persons with asthma in the Jappinen et al. (1990) study, an acute inhalation MRL of 0.07 ppm was derived. An uncertainty factor of 30 was applied to the LOAEL 10 for the use of a LOAEL and 3 for human variability. Since persons with severe asthma were excluded from the study, an uncertainty factor of 3 is needed to protect all sensitive individuals including children. Further details on the derivation of this MRL can be found in the MRL worksheets in Appendix A of this profile. Based on aNOAEL of 30.5 ppm for respiratory effects in mice observed in the CUT (1983a) study, an intermediated MRL of 0.03 ppm was derived. The NOAEL is adjusted for intermittent exposure and the NOAEL[hec] is calculated. An uncertainty factor of 30 is then applied 3 for extrapolating from animals to humans and 10 for human variability. Further details on this MRL can be found in the MRL worksheets in Appendix A of this profile. 

The desired outcome in the pharmacological treatment of asthma is to prevent or relieve the reversible airway obstruction and airway hyperresponsiveness caused by the inflammatory process. Therefore, categories of medications include bronchodilators and anti-inflammatory drugs. 

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