Pathophysiology of asthma


is a common pulmonary condition defined by chronic inflammation of respiratory tubes, tightening of respiratory smooth muscle, and episodes of bronchoconstriction. The Centers for Disease Control and Prevention estimate that 1 in 11 children and 1 in 12 adults have asthma in the United States of America. According to the World Health Organization, asthma affects 235 million people worldwide. There are two major categories of asthma: allergic and non-allergic. The focus of this article will be allergic asthma. In both cases, bronchoconstriction is prominent.

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 asthma patients are "hypersensitive" to certain triggers, also known as stimuli. In response to exposure to these triggers, the bronchi contract into spasm. Inflammation soon follows, leading to a further narrowing of the airways and excessive mucus production, which leads to coughing and other breathing difficulties. Bronchospasm may resolve spontaneously in 1–2 hours, or in about 50% of subjects, may become part of a 'late' response, where this initial insult is followed 3–12 hours later with further bronchoconstriction and inflammation.
The normal caliber of the bronchus is maintained by a balanced functioning of the autonomic nervous system, which both operates reflexively. The parasympathetic reflex loop consists of afferent nerve endings which originate under the inner lining of the bronchus. Whenever these afferent nerve endings are stimulated impulses travel to the brain-stem vagal center, then down the vagal efferent pathway to again reach the bronchial small airways. Acetylcholine is released from the efferent nerve endings. This acetylcholine results in the excessive formation of inositol 1,4,5-trisphosphate in bronchial smooth muscle cells which leads to muscle shortening and this initiates bronchoconstriction.

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 people with asthma and people who are free of the disease, 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 "check" and usually ignore the allergen molecules. In asthma patients, however, these cells transform into a different type of cell, for reasons that are not well understood. A possible reason could be the release of Interleukin-4 by Mast cells that induce differentiation of naive helper T cells to Th2 cells.
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 a patient inhales the same allergen, these antibodies "recognize" it and activate a humoral response. Inflammation results: chemicals are produced that cause the wall of the airway to thicken, cells which produce scarring to proliferate and contribute to further 'airway remodeling', causes mucus producing cells to grow larger and produce more and thicker mucus, and the cell-mediated arm of the immune system is activated. Inflamed airways are more hyper-reactive, and will be more prone to bronchospasm.
The "hygiene hypothesis" postulates that an imbalance in the regulation of these TH cell types in early life leads to a long-term domination of the cells involved in allergic responses over those involved in fighting infection. The suggestion is that for a child being exposed to microbes early in life, taking fewer antibiotics, living in a large family, and growing up in the country stimulate the TH1 response and reduce the odds of developing asthma.
Asthma is associated with a procoagulant state in the bronchoalveolar space.

Stimuli

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 using the Science Citation Index and has been cited more times than any other article in the history of the Journal of Allergy and Clinical Immunology.
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 allergies.

Asthma and sleep apnea

It is recognized with increasing frequency that patients who have both obstructive sleep apnea and 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

If gastro-esophageal reflux disease is present, the patient may have repetitive episodes of acid aspiration. GERD may be common in difficult-to-control asthma, but according to one study, treating it does not seem to affect the asthma.
When there is a clinical suspicion for GERD as the cause of the asthma, an Esophageal pH Monitoring is required to confirm the diagnosis and establish the relationship between GERD and asthma.

Asthma and exposure to air pollution during pregnancy

Asthma affects four to eight out of a hundred pregnant women. This is due to the fact that during pregnancy, there is an immunological shift due to hormonal fluctuations. In some cases, there is an increase in Estrogen levels which in turn reduce the activity of natural killer cells, Th1 cell production of inflammatory cytokines, and production of anti-inflammatory cytokines. As we have seen, these play an important role in the pathophysiology of asthma.
Researchers found a link between the preterm birth and exposure to air pollution in asthmatic pregnant women. Results suggested that women with asthma have a higher risk of preterm birth. Researchers suggested that asthmatic episodes in pregnant women were associated with ongoing exposure to nitrogen dioxide and carbon monoxide - types of air pollutants.
Researchers also studied when women were most susceptible to develop asthma. Data indicated that women were at a higher risk of developing asthma when exposed to pollutants before conception and during pregnancy. In particular, "an increase of 30 parts per billion in nitrogen oxide exposure in the three months prior to pregnancy increased preterm birth risk by nearly 30 percent for women with asthma, compared to 8 percent for women without asthma."
In other studies, Scientists have found a link between asthma in children and prenatal exposure to air pollution. Results from a study that consisted of 65, 000 Canadian children suggested that children of mothers who lived near highways during pregnancy had a 25% increased risk of developing asthma before the age of five when compared with children of mothers who did not live near highways. Highways are a major source of traffic-related air pollution such that there is an accumulation of air pollutants such as nitrogen dioxide and carbon monoxide in the vicinity of highways.
In another study, researchers collected data from 6,000 children attending public schools in California. The results suggested that a high exposure to prenatal air pollution was strongly correlated with increased susceptibility to asthma during childhood.