|
Page: Pathophysiology
Main article
| Home > Allergies > Pathophysiology |
Bronchoconstriction
During an asthma episode, inflamed airways react to environmental triggers such as smoke, dust, or pollen. The airways narrow and produce excess mucus, making it difficult to breathe. In essence, asthma is the result of an immune response in the bronchial airways.
The airways of asthmatics are "hypersensitive" to certain triggers, also known as stimuli (see below). In response to exposure to these triggers, the bronchi (large airways) contract into spasm (an "asthma attack"). Inflammation soon follows, leading to a further narrowing of the airways and excessive mucus production, which leads to coughing and other breathing difficulties.
Stimuli
There are about ten different categories of stimuli:
* Allergenic air pollution, from nature, typically inhaled, which include waste from common household pests, such as the house dust mite and cockroach, grass pollen, mould spores, and pet epithelial cells;
* Medications, including aspirin[8], ?-adrenergic antagonists (beta blockers), and penicillin.
* Food allergies such as milk, peanuts, and eggs. However, asthma is rarely the only symptom, and not all people with food or other allergies have asthma.
* Use of fossil fuel related allergenic air pollution, such as ozone, smog, summer smog, nitrogen dioxide, and sulfur dioxide, which is thought to be one of the major reasons for the high prevalence of asthma in urban areas;
* Various industrial compounds and other chemicals, notably sulfites; chlorinated swimming pools generate chloramines—monochloramine (NH2Cl), dichloramine (NHCl2) and trichloramine (NCl3)—in the air around them, which are known to induce asthma.[9]
* Early childhood infections, especially viral respiratory infections. However, persons of any age can have asthma triggered by colds and other respiratory infections even though their normal stimuli might be from another category (e.g. pollen) and absent at the time of infection. 80% of asthma attacks in adults and 60% in children are caused by respiratory viruses.
* Exercise, the effects of which differ somewhat from those of the other triggers;
* Allergenic indoor air pollution from newsprint & other literature such as, junk mail leaflets & glossy magazines (in some countries).
* Hormonal changes in adolescent girls and adult women associated with their menstrual cycle can lead to a worsening of asthma. Some women also experience a worsening of their asthma during pregnancy whereas others find no significant changes, and in other women their asthma improves during their pregnancy.
* Emotional stress which is poorly understood as a trigger.
[edit] Bronchial inflammation
The mechanisms behind allergic asthma—i.e., asthma resulting from an immune response to inhaled allergens—are the best understood of the causal factors. In both asthmatics and non-asthmatics, inhaled allergens that find their way to the inner airways are ingested by a type of cell known as antigen presenting cells, or APCs. APCs then "present" pieces of the allergen to other immune system cells. In most people, these other immune cells (TH0 cells) "check" and usually ignore the allergen molecules. In asthmatics, however, these cells transform into a different type of cell (TH2), for reasons that are not well understood. The resultant TH2 cells activate an important arm of the immune system, known as the humoral immune system. The humoral immune system produces antibodies against the inhaled allergen. Later, when an asthmatic inhales the same allergen, these antibodies "recognize" it and activate a humoral response. Inflammation results: chemicals are produced that cause the airways to constrict and release more mucus, and the cell-mediated arm of the immune system is activated. The inflammatory response is responsible for the clinical manifestations of an asthma attack. The following section describes this complex series of events in more detail.
Pathogenesis
The fundamental problem in asthma appears to be immunological: young children in the early stages of asthma show signs of excessive inflammation in their airways. Epidemiological findings give clues as to the pathogenesis: the incidence of asthma seems to be increasing worldwide, and asthma is now very much more common in affluent countries.
In 1968 Andor Szentivanyi first described The Beta Adrenergic Theory of Asthma; in which blockage of the Beta-2 receptors of pulmonary smooth muscle cells causes asthma. Szentivanyi's Beta Adrenergic Theory is a citation classic and has been cited more times than any other article in the history of the Journal of Allergy.
In 1995 Szentivanyi and colleagues demonstrated that IgE blocks beta-2 receptors. Since overproduction of IgE is central to all atopic diseases, this was a watershed moment in the world of Allergy.
The Beta-Adrenergic Theory has been cited in the scholarship of such noted investigators as Richard F. Lockey (former President of the American Academy of Allergy, Asthma, and Immunology), Charles Reed (Chief of Allergy at Mayo Medical School), and Craig Venter (Human Genome Project).
Causes
Many studies have linked asthma, bronchitis, and acute respiratory illnesses to air quality experienced by children. One of the largest of these studies is the California Children's Health Study. From the press release
The study showed that children in the high ozone communities who played three or more sports developed asthma at a rate three times higher than those in the low ozone communities. Because participation in some sports can result in a child drawing up to 17 times the “normal” amount of air into the lungs, young athletes are more likely to develop asthma.
Note that concentrations of ozone have risen steadily in Europe since 1870.
Another theory of pathogenesis is that asthma is a disease of hygiene. In nature, babies are exposed to bacteria and other antigens soon after birth, "switching on" the TH1 lymphocyte cells of the immune system that deal with bacterial infection. If this stimulus is insufficient, as it may be in modern, clean environments, then TH2 cells predominate, and asthma and other allergic diseases may develop. This "hygiene hypothesis" may explain the increase in asthma in affluent populations. The TH2 lymphocytes and eosinophil cells that protect us against parasites and other infectious agents are the same cells responsible for the allergic reaction. The Charcot-Leyden crystals are formed when the crystalline material in eosinophils coalesce. These crystals are significant in sputum samples of people with asthma. In the developed world, these parasites are now rarely encountered, but the immune response remains and is wrongly triggered in some individuals by certain allergens.
Finally, it has been postulated that some forms of asthma may be related to infection, in particular by Chlamydia pneumoniae. This issue remains controversial, as the relationship is not borne out by meta-analysis of the research. The correlation seems to be not with the onset, but rather with accelerated loss of lung function in adults with new onset of non-atopic asthma. One possible explanation is that some asthmatics may have altered immune response that facilitates long-term chlamydia pneumonia infection. The response to targeting with macrolide antibiotics has been investigated, but the temporary benefit reported in some studies may reflect just their anti-inflammatory activities rather than their antimicrobic action.
Asthma and sleep apnea
Main article: sleep apnea
It is recognized with increasing frequency, that patients who have both obstructive sleep apnea (OSA) and bronchial asthma, often improve tremendously when the sleep apnea is diagnosed and treated. CPAP is not effective in patients with nocturnal asthma only.
Asthma and gastro-esophageal reflux disease
Main article: gastro-esophageal reflux disease
If gastro-esophageal reflux disease is present, the patient may have repetitive episodes of acid aspiration, which results in airway inflammation and "irritant-induced" asthma.[citation needed] GERD may be common in difficult-to-control asthma, but generally speaking, treating it does not seem to affect the asthma.
|
Important notice:
The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other
qualified health provider with any questions you may have regarding a medical condition.
|