Asthma - Definition and Overview

Asthma is an immunological disease which causes difficulty in breathing. It is a form of type II hypersensitivity in which the bronchioles in the lungs are narrowed by inflammation and spasm of the lining of the airway wall. A person with asthma may experience wheezing, shortness of breath and poor exercise tolerance.

Pathology

• Activation of mast cells by allergens causing release of large amounts of histamine and IgE
• Infiltration of bronchial mucosa (the lining of the airway) by lymphocytes
• Swelling (oedema) of bronchial mucosa
• Thickening of smooth muscle of bronchioles
• Increased eosinophil granulocytes
• Mucus plugs
• Remodeling (distortion) of the airway

Pathogenesis

• The fundamental problem seems to be immunological: young children in the early stages of asthma show signs of excessive inflammation in their airways.
• Epidemiology gives clues to the pathogenesis: the incidence of asthma seems to be increasing worldwide; asthma is more common in more affluent countries, and more common in higher socioeconomic groups within countries.
• One theory is that it is a disease of hygiene. In nature, babies are exposed to bacteria soon after birth, "switching on" the Th1 lymphocyte cells of the immune system which deal with bacterial infection. If this stimulus is insufficient (as, perhaps, in modern clean environments) then asthma and other allergic diseases may develop. This "Hygiene Hypothesis" may explain the increase in asthma in affluent populations.
• Related to the above is another theory regarding the part of our immune system which helps protect us against parasites, such as tapeworms. The Th2 lymphocytes and eosinophil cells which protect us against worms are the same cells responsible for the allergic reaction. In the Western world these parasites are now rarely encountered but the immune response remains and is triggered in some individuals by certain allergens.
• A third theory blames the rise on asthma on air pollution. While it is well known that substantial exposures to certain industrial chemicals can cause acute episodes of asthma, it has not been proven that the same is responsible for the development of asthma. In Western Europe, most atmospheric pollutants have fallen significantly in the last forty years while the prevalence of asthma has risen.
• Typical triggers include:
  • inhaled allergens such as house dust mite and cockroach, grass pollen, mould spores and pet epithelial cells.
  • cold air
  • exercise
  • respiratory infection
  • emotional stress
  • aspirin & similar medications

Symptoms

The cardinal symptom of asthma is wheezing, indicating airway obstruction. Cough, sometimes with clear sputum may be present. Typically the symptoms are very variable, often with rapid onset, and associated with the triggers listed above. Symptoms are often worse during the night or on waking. Increasing airway obstruction will cause shortness of breath. Asthma sometimes correlates with acid indigestion, especially amongst older patients.

Signs

"Signs" (what a physician finds on examination) are wheeze, rapid breathing, expiratory phase of breathing longer than inspiratory, in drawing of tissues between ribs and above sternum & clavicles, over inflation of the chest and rhonchi (wheezy noises heard with a stethoscope). In severe attacks the asthma sufferer may be cyanosed (blue), may have chest pain and can lose consciousness. Between attacks a person with asthma may show no signs at all.

Diagnosis

In most cases the physician can make the diagnosis on the basis of typical symptoms and signs. The typical rapid changes in airway obstruction can be demonstrated by a fall in pulmonary function tests spontaneously, after exercise or inhalation of histamine or methacholine, and subsequent improvement with an inhaled bronchodilator medication. Many people with asthma have allergies; positive allergy tests support a diagnosis of asthma and may help in identifying avoidable triggers. Other tests (for example chest x-ray) may be required to exclude other lung disease.

Treatment

Symptomatic

Episodes of wheeze and shortness of breath generally respond to inhaled bronchodilators which work by relaxing the smooth muscle in the walls of the bronchi (airways). More severe episodes may need short courses of oral steroids which suppress inflammation and reduce the swelling of the lining of the airway.

• Bronchodilators (usually inhaled)
  • Short-acting selective beta₂-adrenoceptor agonists (ex. albuterol (salbutamol), terbutaline)
  • Antimuscarinics (ex. ipratropium, oxitropium)
  • Older treatments which have a less selective effect on adrenergic receptors are inhaled epinephrine and ephedrine tablets; unlike other treatments both are available over the counter in the US (as Primatene (http://www.primatene.com))
• Systemic steroids (ex. prednisone, prednisolone, dexamethasone)
• Oxygen to alleviate the hypoxia (but not the asthma per se) that is the result of extreme asthma attacks³.
• If chronic acid indigestion (GERD) is part of the attack, it is necessary to treat it as well or it will restart the inflammatory process¹.

Preventive

Triggers such as pets and aspirin² should be identified and managed. People with asthma who are having symptoms most days will usually benefit from regular preventive medication. The most effective preventive medication are the inhaled steroids.

• Inhaled corticosteroids (ex. fluticasone, budesonide, beclomethasone, mometasone)
• Leukotriene antagonists (ex. montelukast sodium (Singulair (http://www.singulair.com)), zafirlukast)
• Long-acting beta₂-adrenoceptor agonists (ex. salmeterol, formoterol)
• Mast cell stabilizers (ex. cromolyn sodium (sodium cromoglycate), nedocromil)

External links

• Schwartz, Wendy. (1999). Supporting Students with Asthma (http://www.ericdigests.org/2000-4/asthma.htm). ERIC/CUE Digest Series (http://www.ericdigests.org/), #151.
• Lungs OnLine - Asthma (http://www.lungsonline.com/asthma.html)
• MedlinePlus: Asthma (http://www.nlm.nih.gov/medlineplus/asthma.html)
• Kelly, Evelyn B. (2004). Diseases and Disorders:Asthma (http://pubs.acs.org/subscribe/journals/mdd/v07/i07/pdf/704diseases.pdf). Modern Drug Discovery 7 (7), 51-53 (http://pubs.acs.org/subscribe/journals/mdd/v07/i07/toc/toc_i07.html).

Brief overview of history and symptoms with information on long-term medication of the condition and emerging biotech drugs

References

the references here are not the only available for each referring topic, nor are they necessarily the latest or best; they provide basic substantiating evidence for statements and starting points for further research into the literature

Note 1: Mujica, V.R.; Rao, S.S. (1999). Recognizing atypical manifestations of GERD. Asthma, chest pain, and otolaryngologic disorders may be due to reflux. Postgraduage Medical Journal. 105(1), 53-55+. PMID 9924493

Note 2: Jenkins, C.; Costello, J.; Hodge, L. (2004). Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice. British Medical Journal (Clinical Research Edition). 328(7437), 434. PMID 14976098

Note 3: Inwald, D.; Roland, M.; Kuitert, L.; McKenzie, S.A.; and Petros, A. (2001). Oxygen treatment for acute severe asthma. British Medical Journal (Clinical Research Edition). 323(7304), 98-100. PMID 11451788