Genetic
CD14-endotoxin interaction based on CD14 SNP C-159T[49] | ||
Endotoxin levels | CC genotype | TT genotype |
High exposure | Low risk | High risk |
Low exposure | High risk | Low risk |
Family history is a risk factor for asthma with many different genes being implicated.[50] If one identical twin is affected, the probability of the other having the disease is approximately 25%.[50] By the end of 2005, 25 genes had been associated with asthma in six or more separate populations including:GSTM1, IL10, CTLA-4, SPINK5,LTC4S, IL4R and ADAM33 among others.[51] Many of these genes are related to the immune system or modulating inflammation. Even among this list of genes supported by highly replicated studies, results have not been consistent among all populations tested.[51] In 2006 over 100genes were associated with asthma in one genetic association study alone;[51] more continue to be found.[52]
Some genetic variants may only cause asthma when they are combined with specific environmental exposures.[4] An example is a specific single nucleotide polymorphism in the CD14 region and exposure to endotoxin (a bacterial product). Endotoxin exposure can come from several environmental sources including tobacco smoke, dogs, and farms. Risk for asthma, then, is determined by both a person's genetics and the level of endotoxin exposure.
Medical conditions
A triad of atopic eczema, allergic rhinitis and asthma is calledatopy.[53] The strongest risk factor for developing asthma is a history of atopic disease;[40] with asthma occurring at a much greater rate in those who have either eczema or hay fever.[54] Asthma has been associated with Churg–Strauss syndrome, an autoimmune disease and vasculitis. Individuals with certain types of urticaria may also experience symptoms of asthma.[53]
There is a correlation between obesity and the risk of asthma with both having increased in recent years.[55][56] Several factors may be at play including decreased respiratory function due to a buildup of fat and the fact that adipose tissue leads to a pro-inflammatory state.[57]
Beta blocker medications such as propranolol can trigger asthma in those who are susceptible.[58] Cardioselective beta-blockers, however, appear safe in those with mild or moderate disease.[59] Other medications that can cause problems are ASA, NSAIDs, and angiotensin-converting enzyme inhibitors.
Exacerbation
Some individuals will have stable asthma for weeks or months and then suddenly develop an episode of acute asthma. Different individuals react differently to various factors.[61]Most individuals can develop severe exacerbation from a number of triggering agents.[61]
Home factors that can lead to exacerbation of asthma include dust, animal dander (especially cat and dog hair), cockroach allergens and mold.[61] Perfumes are a common cause of acute attacks in women and children. Both viral and bacterial infections of the upper respiratory tract can worsen the disease.[61] Psychological stress may worsen symptoms—it is thought that stress alters the immune system and thus increases the airway inflammatory response to allergens and irritants.
Pathophysiology
Main article: Pathophysiology of asthma
Obstruction of the lumen of a bronchiolebymucoid exudate, goblet cell metaplasia, and epithelial basement membrane thickening in a person with asthma.
Asthma is the result of chronic inflammation of the airways which subsequently results in increased contractability of the surroundingsmooth muscles. This among other factors leads to bouts of narrowing of the airway and the classic symptoms of wheezing. The narrowing is typically reversible with or without treatment. Occasionally the airways themselves change.[16] Typical changes in the airways include an increase in eosinophils and thickening of the lamina reticularis. Chronically the airways' smooth muscle may increase in size along with an increase in the numbers of mucous glands. Other cell types involved include: T lymphocytes, macrophages, andneutrophils. There may also be involvement of other components of the immune system including: cytokines, chemokines, histamine, and leukotrienes among others.[41]
Diagnosis
While asthma is a well recognized condition, there is not one universal agreed upon definition.[41] It is defined by the Global Initiative for Asthma as "a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction within the lung that is often reversible either spontaneously or with treatment".[16]
There is currently no precise test with the diagnosis typically based on the pattern of symptoms and response to therapy over time.[5][41] A diagnosis of asthma should be suspected if there is a history of: recurrent wheezing, coughing or difficulty breathing and these symptoms occur or worsen due to exercise, viral infections, allergens or air pollution.[63] Spirometry is then used to confirm the diagnosis.[63] In children under the age of six the diagnosis is more difficult as they are too young for spirometry.[64]
Spirometry
Spirometry is recommended to aid in diagnosis and management.[65][66] It is the single best test for asthma. If the FEV1 measured by this technique improves more than 12% following administration of a bronchodilator such as salbutamol, this is supportive of the diagnosis.[67] It however may be normal in those with a history of mild asthma, not currently acting up. Single-breath diffusing capacity can help differentiate asthma from COPD.[41] It is reasonable to perform spirometry every one or two years to follow how well a person's asthma is controlled.[68]
Others
The methacholine challenge involves the inhalation of increasing concentrations of a substance that causes airway narrowing in those predisposed. If negative it means that a person does not have asthma; if positive, however, it is not specific for the disease.[41]
Other supportive evidence includes: a ≥20% difference in peak expiratory flow rate on at least three days in a week for at least two weeks, a ≥20% improvement of peak flow following treatment with either salbutamol, inhaled corticosteroids or prednisone, or a ≥20% decrease in peak flow following exposure to a trigger.[69] Testing peak expiratory flow is more variable than spirometry, however, and thus not recommended for routine diagnosis. It may be useful for daily self-monitoring in those with moderate to severe disease and for checking the effectiveness of new medications. It may also be helpful in guiding treatment in those with acute exacerbations.[70]
Classification
Asthma is clinically classified according to the frequency of symptoms, forced expiratory volume in one second (FEV1), and peak expiratory flow rate.[6] Asthma may also be classified as atopic (extrinsic) or non-atopic (intrinsic), based on whether symptoms are precipitated by allergens (atopic) or not (non-atopic).[7]While asthma is classified based on severity, at the moment there is no clear method for classifying different subgroups of asthma beyond this system.[71]Finding ways to identify subgroups that respond well to different types of treatments is a current critical goal of asthma research.[71]
Although asthma is a chronic obstructive condition, it is not considered as a part of chronic obstructive pulmonary disease as this term refers specifically to combinations of disease that are irreversible such as bronchiectasis, chronic bronchitis, and emphysema.[72] Unlike these diseases, the airway obstruction in asthma is usually reversible; however, if left untreated, the chronic inflammation from asthma can lead the lungs to become irreversibly obstructed due to airway remodeling.[73] In contrast to emphysema, asthma affects the bronchi, not the alveoli.
Asthma exacerbation
An acute asthma exacerbation is commonly referred to as an asthma attack. The classic symptoms are shortness of breath, wheezing, and chest tightness.[41] While these are the primary symptoms of asthma,[76] some people present primarily with coughing, and in severe cases, air motion may be significantly impaired such that no wheezing is heard.[75]
Signs which occur during an asthma attack include the use of accessory muscles of respiration (sternocleidomastoid and scalene muscles of the neck), there may be a paradoxical pulse (a pulse that is weaker during inhalation and stronger during exhalation), and over-inflation of the chest.[77] Ablue color of the skin and nails may occur from lack of oxygen.[78]
In a mild exacerbation the peak expiratory flow rate (PEFR) is ≥200 L/min or ≥50% of the predicted best.[79] Moderate is defined as between 80 and 200 L/min or 25% and 50% of the predicted best while severe is defined as ≤ 80 L/min or ≤25% of the predicted best.[79]
Acute severe asthma, previously known as status asthmaticus, is an acute exacerbation of asthma that does not respond to standard treatments of bronchodilators and corticosteroids.[80] Half of cases are due to infections with others caused by allergen, air pollution, or insufficient or inappropriate medication use.[80]
Brittle asthma is a kind of asthma distinguishable by recurrent, severe attacks.[75] Type 1 brittle asthma is a disease with wide peak flow variability, despite intense medication. Type 2 brittle asthma is background well-controlled asthma with sudden severe exacerbations.[75]
Exercise-induced
Main article: Exercise-induced bronchoconstriction
Exercise can trigger bronchoconstriction in both people with and without asthma.[81] It occurs in most people with asthma and up to 20% of people without asthma.[81] In athletes it occurs more common in elite athletes, with rates varying from 3% for bobsled racers to 50% forcycling and 60% for cross-country skiing.[81] While it may occur with any weather conditions it is more common when it is dry and cold.[82] Inhaled beta2-agonists do not appear to improve athletic performance among those without asthma[83] however oral doses may improve endurance and strength.
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