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Wikipedia

Asthma

February 15, 2024

For other uses, see Asthma (disambiguation).
Not to be confused with Ahimsa.

Asthma is a long-term inflammatory disease of the airways of the lungs.[5] It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms.[10][11] Symptoms include episodes of wheezing, coughing, chest tightness, and shortness of breath.[4] These may occur a few times a day or a few times per week.[5] Depending on the person, asthma symptoms may become worse at night or with exercise.[5]

Asthma
Peak flow meters are used to measure the peak expiratory flow rate, important in both monitoring and diagnosing asthma.[1]
Pronunciation
SpecialtyPulmonology
SymptomsRecurring episodes of wheezing, coughing, chest tightness, shortness of breath[4]
ComplicationsGastroesophageal reflux disease (GERD), sinusitis, obstructive sleep apnea
Usual onsetChildhood
DurationLong term[5]
CausesGenetic and environmental factors[4]
Risk factorsAir pollution, allergens[5]
Diagnostic methodBased on symptoms, response to therapy, spirometry[6]
TreatmentAvoiding triggers, inhaled corticosteroids, salbutamol[7][8]
Frequencyapprox. 262 million (2019)[9]
Deathsapprox. 461,000 (2019)[9]

Asthma is thought to be caused by a combination of genetic and environmental factors.[4] Environmental factors include exposure to air pollution and allergens.[5] Other potential triggers include medications such as aspirin and beta blockers.[5] Diagnosis is usually based on the pattern of symptoms, response to therapy over time, and spirometry lung function testing.[6] Asthma is classified according to the frequency of symptoms, forced expiratory volume in one second (FEV1), and peak expiratory flow rate.[12] It may also be classified as atopic or non-atopic, where atopy refers to a predisposition toward developing a type 1 hypersensitivity reaction.[13][14]

There is no known cure for asthma, but it can be controlled.[5] Symptoms can be prevented by avoiding triggers, such as allergens and respiratory irritants, and suppressed with the use of inhaled corticosteroids.[7][15] Long-acting beta agonists (LABA) or antileukotriene agents may be used in addition to inhaled corticosteroids if asthma symptoms remain uncontrolled.[16][17] Treatment of rapidly worsening symptoms is usually with an inhaled short-acting beta2 agonist such as salbutamol and corticosteroids taken by mouth.[8] In very severe cases, intravenous corticosteroids, magnesium sulfate, and hospitalization may be required.[18]

In 2019 asthma affected approximately 262 million people and caused approximately 461,000 deaths.[9] Most of the deaths occurred in the developing world.[5] Asthma often begins in childhood,[5] and the rates have increased significantly since the 1960s.[19] Asthma was recognized as early as Ancient Egypt.[20] The word asthma is from the Greek ἆσθμα, âsthma, which means 'panting'.[21]

Signs and symptoms

 
Wheezing
The sound of wheezing as heard with a stethoscope.
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Asthma is characterized by recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing.[22] Sputum may be produced from the lung by coughing but is often hard to bring up.[23] During recovery from an asthma attack (exacerbation), it may appear pus-like due to high levels of white blood cells called eosinophils.[24] Symptoms are usually worse at night and in the early morning or in response to exercise or cold air.[25] Some people with asthma rarely experience symptoms, usually in response to triggers, whereas others may react frequently and readily and experience persistent symptoms.[26]

Associated conditions

A number of other health conditions occur more frequently in people with asthma, including gastroesophageal reflux disease (GERD), rhinosinusitis, and obstructive sleep apnea.[27] Psychological disorders are also more common,[28] with anxiety disorders occurring in between 16 and 52% and mood disorders in 14–41%.[29] It is not known whether asthma causes psychological problems or psychological problems lead to asthma.[30] Current asthma, but not former asthma, is associated with increased all-cause mortality, heart disease mortality, and chronic lower respiratory tract disease mortality.[31] Asthma, particularly severe asthma, is strongly associated with development of chronic obstructive pulmonary disease (COPD).[32][33][34] Those with asthma, especially if it is poorly controlled, are at increased risk for radiocontrast reactions.[35]

Cavities occur more often in people with asthma.[36] This may be related to the effect of beta2 agonists decreasing saliva.[37] These medications may also increase the risk of dental erosions.[37]

Causes

Asthma is caused by a combination of complex and incompletely understood environmental and genetic interactions.[38][39] These influence both its severity and its responsiveness to treatment.[40] It is believed that the recent increased rates of asthma are due to changing epigenetics (heritable factors other than those related to the DNA sequence) and a changing living environment.[41] Asthma that starts before the age of 12 years old is more likely due to genetic influence, while onset after age 12 is more likely due to environmental influence.[42]

Environmental

See also: Asthma-related microbes

Many environmental factors have been associated with asthma's development and exacerbation, including allergens, air pollution, and other environmental chemicals.[43] There are some substances that are known to cause asthma in exposed people and they are called asthmagens. Some common asthmagens include ammonia, latex, pesticides, solder and welding fumes, metal or wood dusts, spraying of isocyanate paint in vehicle repair, formaldehyde, glutaraldehyde, anhydrides, glues, dyes, metal working fluids, oil mists, molds.[44][45] Smoking during pregnancy and after delivery is associated with a greater risk of asthma-like symptoms.[46] Low air quality from environmental factors such as traffic pollution or high ozone levels[47] has been associated with both asthma development and increased asthma severity.[48] Over half of cases in children in the United States occur in areas when air quality is below the EPA standards.[49] Low air quality is more common in low-income and minority communities.[50]

Exposure to indoor volatile organic compounds may be a trigger for asthma; formaldehyde exposure, for example, has a positive association.[51] Phthalates in certain types of PVC are associated with asthma in both children and adults.[52][53] While exposure to pesticides is linked to the development of asthma, a cause and effect relationship has yet to be established.[54][55] A meta-analysis concluded gas stoves are a major risk factor for asthma, finding around one in eight cases in the U.S. could be attributed to these.[56]

The majority of the evidence does not support a causal role between paracetamol (acetaminophen) or antibiotic use and asthma.[57][58] A 2014 systematic review found that the association between paracetamol use and asthma disappeared when respiratory infections were taken into account.[59] Maternal psychological stress during pregnancy is a risk factor for the child to develop asthma.[60]

Asthma is associated with exposure to indoor allergens.[61] Common indoor allergens include dust mites, cockroaches, animal dander (fragments of fur or feathers), and mold.[62][63] Efforts to decrease dust mites have been found to be ineffective on symptoms in sensitized subjects.[64][65] Weak evidence suggests that efforts to decrease mold by repairing buildings may help improve asthma symptoms in adults.[66] Certain viral respiratory infections, such as respiratory syncytial virus and rhinovirus,[21] may increase the risk of developing asthma when acquired as young children.[67] Certain other infections, however, may decrease the risk.[21]

Hygiene hypothesis

The hygiene hypothesis attempts to explain the increased rates of asthma worldwide as a direct and unintended result of reduced exposure, during childhood, to non-pathogenic bacteria and viruses.[68][69] It has been proposed that the reduced exposure to bacteria and viruses is due, in part, to increased cleanliness and decreased family size in modern societies.[70] Exposure to bacterial endotoxin in early childhood may prevent the development of asthma, but exposure at an older age may provoke bronchoconstriction.[71] Evidence supporting the hygiene hypothesis includes lower rates of asthma on farms and in households with pets.[70]

Use of antibiotics in early life has been linked to the development of asthma.[72] Also, delivery via caesarean section is associated with an increased risk (estimated at 20–80%) of asthma – this increased risk is attributed to the lack of healthy bacterial colonization that the newborn would have acquired from passage through the birth canal.[73][74] There is a link between asthma and the degree of affluence which may be related to the hygiene hypothesis as less affluent individuals often have more exposure to bacteria and viruses.[75]

Genetic

CD14-endotoxin interaction based on CD14 SNP C-159T[76]
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.[77] If one identical twin is affected, the probability of the other having the disease is approximately 25%.[77] 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.[78] 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.[78] In 2006 over 100 genes were associated with asthma in one genetic association study alone;[78] more continue to be found.[79]

Some genetic variants may only cause asthma when they are combined with specific environmental exposures.[38] 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.[76]

Medical conditions

A triad of atopic eczema, allergic rhinitis and asthma is called atopy.[80] The strongest risk factor for developing asthma is a history of atopic disease;[67] with asthma occurring at a much greater rate in those who have either eczema or hay fever.[81] Asthma has been associated with eosinophilic granulomatosis with polyangiitis (formerly known as Churg–Strauss syndrome), an autoimmune disease and vasculitis.[82] Individuals with certain types of urticaria may also experience symptoms of asthma.[80]

There is a correlation between obesity and the risk of asthma with both having increased in recent years.[83][84] 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.[85]

Beta blocker medications such as propranolol can trigger asthma in those who are susceptible.[86] Cardioselective beta-blockers, however, appear safe in those with mild or moderate disease.[87][88] Other medications that can cause problems in asthmatics are angiotensin-converting enzyme inhibitors, aspirin, and NSAIDs.[89] Use of acid suppressing medication (proton pump inhibitors and H2 blockers) during pregnancy is associated with an increased risk of asthma in the child.[90]

Exacerbation

Some individuals will have stable asthma for weeks or months and then suddenly develop an episode of acute asthma. Different individuals react to various factors in different ways.[91] Most individuals can develop severe exacerbation from a number of triggering agents.[91]

Home factors that can lead to exacerbation of asthma include dust, animal dander (especially cat and dog hair), cockroach allergens and mold.[91][92] 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.[91] 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.[48][93]

Asthma exacerbations in school‐aged children peak in autumn, shortly after children return to school. This might reflect a combination of factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. There is limited evidence to guide possible approaches to reducing autumn exacerbations, but while costly, seasonal omalizumab treatment from four to six weeks before school return may reduce autumn asthma exacerbations.[94]

Pathophysiology

Main article: Pathophysiology of asthma
 
Figure A shows the location of the lungs and airways in the body. Figure B shows a cross-section of a normal airway. Figure C shows a cross-section of an airway during asthma symptoms.
 
Obstruction of the lumen of a bronchiole by mucoid exudate, goblet cell metaplasia, and epithelial basement membrane thickening in a person with asthma
 
Diagram of asthma

Asthma is the result of chronic inflammation of the conducting zone of the airways (most especially the bronchi and bronchioles), which subsequently results in increased contractability of the surrounding smooth 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.[22] 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, and neutrophils. There may also be involvement of other components of the immune system, including cytokines, chemokines, histamine, and leukotrienes among others.[21]

Diagnosis

While asthma is a well-recognized condition, there is not one universal agreed upon definition.[21] 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".[22]

There is currently no precise test for the diagnosis, which is typically based on the pattern of symptoms and response to therapy over time.[6][21] Asthma may 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.[95] Spirometry is then used to confirm the diagnosis.[95] In children under the age of six the diagnosis is more difficult as they are too young for spirometry.[96]

Spirometry

Spirometry is recommended to aid in diagnosis and management.[97][98] It is the single best test for asthma. If the FEV1 measured by this technique improves more than 12% and increases by at least 200 milliliters following administration of a bronchodilator such as salbutamol, this is supportive of the diagnosis. It however may be normal in those with a history of mild asthma, not currently acting up.[21] As caffeine is a bronchodilator in people with asthma, the use of caffeine before a lung function test may interfere with the results.[99] Single-breath diffusing capacity can help differentiate asthma from COPD.[21] It is reasonable to perform spirometry every one or two years to follow how well a person's asthma is controlled.[100]

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.[21]

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.[101] 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.[102]

Classification

Clinical classification (≥ 12 years old)[12]
Severity Symptom frequency Night-time symptoms %FEV1 of predicted FEV1 variability SABA use
Intermittent ≤2/week ≤2/month ≥80% <20% ≤2 days/week
Mild persistent >2/week 3–4/month ≥80% 20–30% >2 days/week
Moderate persistent Daily >1/week 60–80% >30% daily
Severe persistent Continuously Frequent (7/week) <60% >30% ≥twice/day

Asthma is clinically classified according to the frequency of symptoms, forced expiratory volume in one second (FEV1), and peak expiratory flow rate.[12] 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).[13] While asthma is classified based on severity, at the moment there is no clear method for classifying different subgroups of asthma beyond this system.[103] Finding ways to identify subgroups that respond well to different types of treatments is a current critical goal of asthma research.[103] Recently, asthma has been classified based on whether it is associated with type 2 or non–type 2 inflammation. This approach to immunologic classification is driven by a developing understanding of the underlying immune processes and by the development of therapeutic approaches that target type 2 inflammation.[104]

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 and emphysema.[105] 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.[106] In contrast to emphysema, asthma affects the bronchi, not the alveoli.[107] The combination of asthma with a component of irreversible airway obstruction has been termed the asthma-chronic obstructive disease (COPD) overlap syndrome (ACOS). Compared to other people with "pure" asthma or COPD, people with ACOS exhibit increased morbidity, mortality and possibly more comorbidities.[108]

Asthma exacerbation

Severity of an acute exacerbation[109]
Near-fatal High PaCO2, or requiring mechanical ventilation, or both
Life-threatening
(any one of)
Clinical signs Measurements
Altered level of consciousness Peak flow < 33%
Exhaustion Oxygen saturation < 92%
Arrhythmia PaO2 < 8 kPa
Low blood pressure "Normal" PaCO2
Cyanosis
Silent chest
Poor respiratory effort
Acute severe
(any one of)
Peak flow 33–50%
Respiratory rate ≥ 25 breaths per minute
Heart rate ≥ 110 beats per minute
Unable to complete sentences in one breath
Moderate Worsening symptoms
Peak flow 50–80% best or predicted
No features of acute severe asthma

An acute asthma exacerbation is commonly referred to as an asthma attack. The classic symptoms are shortness of breath, wheezing, and chest tightness.[21] The wheezing is most often when breathing out.[110] While these are the primary symptoms of asthma,[111] some people present primarily with coughing, and in severe cases, air motion may be significantly impaired such that no wheezing is heard.[109] In children, chest pain is often present.[112]

Signs occurring 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.[113] A blue color of the skin and nails may occur from lack of oxygen.[114]

In a mild exacerbation the peak expiratory flow rate (PEFR) is ≥200 L/min, or ≥50% of the predicted best.[115] 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.[115]

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.[116] Half of cases are due to infections with others caused by allergen, air pollution, or insufficient or inappropriate medication use.[116]

Brittle asthma is a kind of asthma distinguishable by recurrent, severe attacks.[109] 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.[109]

Exercise-induced

Main article: Exercise-induced bronchoconstriction

Exercise can trigger bronchoconstriction both in people with or without asthma.[117] It occurs in most people with asthma and up to 20% of people without asthma.[117] Exercise-induced bronchoconstriction is common in professional athletes. The highest rates are among cyclists (up to 45%), swimmers, and cross-country skiers.[118] While it may occur with any weather conditions, it is more common when it is dry and cold.[119] Inhaled beta2 agonists do not appear to improve athletic performance among those without asthma;[120] however, oral doses may improve endurance and strength.[121][122]

Occupational

Main article: Occupational asthma

Asthma as a result of (or worsened by) workplace exposures is a commonly reported occupational disease.[123] Many cases, however, are not reported or recognized as such.[124][125] It is estimated that 5–25% of asthma cases in adults are work-related. A few hundred different agents have been implicated, with the most common being isocyanates, grain and wood dust, colophony, soldering flux, latex, animals, and aldehydes. The employment associated with the highest risk of problems include those who spray paint, bakers and those who process food, nurses, chemical workers, those who work with animals, welders, hairdressers and timber workers.[123]

Aspirin-exacerbated respiratory disease

Main article: Aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease (AERD), also known as aspirin-induced asthma, affects up to 9% of asthmatics.[126] AERD consists of asthma, nasal polyps, sinus disease, and respiratory reactions to aspirin and other NSAID medications (such as ibuprofen and naproxen).[127] People often also develop loss of smell and most experience respiratory reactions to alcohol.[128]

Alcohol-induced asthma

Main article: Alcohol-induced respiratory reactions

Alcohol may worsen asthmatic symptoms in up to a third of people.[129] This may be even more common in some ethnic groups such as the Japanese and those with aspirin-exacerbated respiratory disease.[129] Other studies have found improvement in asthmatic symptoms from alcohol.[129]

Non-atopic asthma

Non-atopic asthma, also known as intrinsic or non-allergic, makes up between 10 and 33% of cases. There is negative skin test to common inhalant allergens. Often it starts later in life, and women are more commonly affected than men. Usual treatments may not work as well.[130] The concept that "non-atopic" is synonymous with "non-allergic" is called into question by epidemiological data that the prevalence of asthma is closely related to the serum IgE level standardized for age and sex (P<0.0001), indicating that asthma is almost always associated with some sort of IgE-related reaction and therefore has an allergic basis, although not all the allergic stimuli that cause asthma appear to have been included in the battery of aeroallergens studied (the "missing antigen(s)" hypothesis).[131] For example, an updated systematic review and meta-analysis of population-attributable risk (PAR) of Chlamydia pneumoniae biomarkers in chronic asthma found that the PAR for C. pneumoniae-specific IgE was 47%.[132]

Infectious asthma

Infectious asthma is an easily identified clinical presentation.[133] When queried, asthma patients may report that their first asthma symptoms began after an acute lower respiratory tract illness. This type of history has been labelled the "infectious asthma" (IA) syndrome,[134] or as "asthma associated with infection" (AAWI)[135] to distinguish infection-associated asthma initiation from the well known association of respiratory infections with asthma exacerbations. Reported clinical prevalences of IA for adults range from around 40% in a primary care practice[134] to 70% in a specialty practice treating mainly severe asthma patients.[136] Additional information on the clinical prevalence of IA in adult-onset asthma is unavailable because clinicians are not trained to elicit this type of history routinely, and recollection in child-onset asthma is challenging. A population-based incident case-control study in a geographically defined area of Finland reported that 35.8% of new-onset asthma cases had experienced acute bronchitis or pneumonia in the year preceding asthma onset, representing a significantly higher risk compared to randomly selected controls (Odds ratio 7.2, 95% confidence interval 5.2-10).[137]

Phenotyping and endotyping

Main article: Asthma phenotyping and endotyping

Asthma phenotyping and endotyping has emerged as a novel approach to asthma classification inspired by precision medicine which separates the clinical presentations of asthma, or asthma phenotypes, from their underlying causes, or asthma endotypes. The best-supported endotypic distinction is the type 2-high/type 2-low distinction. Classification based on type 2 inflammation is useful in predicting which patients will benefit from targeted biologic therapy.[138][139]

Differential diagnosis

Many other conditions can cause symptoms similar to those of asthma. In children, symptoms may be due to other upper airway diseases such as allergic rhinitis and sinusitis, as well as other causes of airway obstruction including foreign body aspiration, tracheal stenosis, laryngotracheomalacia, vascular rings, enlarged lymph nodes or neck masses.[140] Bronchiolitis and other viral infections may also produce wheezing.[141] According to European Respiratory Society, it may not be suitable to label wheezing preschool children with the term "asthma" because there is lack of clinical data on inflammation in airways.[142] In adults, COPD, congestive heart failure, airway masses, as well as drug-induced coughing due to ACE inhibitors may cause similar symptoms. In both populations vocal cord dysfunction may present similarly.[140]

Chronic obstructive pulmonary disease can coexist with asthma and can occur as a complication of chronic asthma. After the age of 65, most people with obstructive airway disease will have asthma and COPD. In this setting, COPD can be differentiated by increased airway neutrophils, abnormally increased wall thickness, and increased smooth muscle in the bronchi. However, this level of investigation is not performed due to COPD and asthma sharing similar principles of management: corticosteroids, long-acting beta-agonists, and smoking cessation.[143] It closely resembles asthma in symptoms, is correlated with more exposure to cigarette smoke, an older age, less symptom reversibility after bronchodilator administration, and decreased likelihood of family history of atopy.[144][145]

Prevention

The evidence for the effectiveness of measures to prevent the development of asthma is weak.[146] The World Health Organization recommends decreasing risk factors such as tobacco smoke, air pollution, chemical irritants including perfume, and the number of lower respiratory infections.[147][148] Other efforts that show promise include: limiting smoke exposure in utero, breastfeeding, and increased exposure to daycare or large families, but none are well supported enough to be recommended for this indication.[146]

Early pet exposure may be useful.[149] Results from exposure to pets at other times are inconclusive[150] and it is only recommended that pets be removed from the home if a person has allergic symptoms to said pet.[151]

Dietary restrictions during pregnancy or when breastfeeding have not been found to be effective at preventing asthma in children and are not recommended.[151] Omega-3 consumption, mediterranean diet and anti-oxidants have been suggested by some studies that might help preventing crisis but the evidence is still inconclusive.[152]

Reducing or eliminating compounds known to sensitive people from the work place may be effective.[123] It is not clear if annual influenza vaccinations affects the risk of exacerbations.[153] Immunization, however, is recommended by the World Health Organization.[154] Smoking bans are effective in decreasing exacerbations of asthma.[155]

Management

While there is no cure for asthma, symptoms can typically be improved.[156] The most effective treatment for asthma is identifying triggers, such as cigarette smoke, pets or other allergens, and eliminating exposure to them. If trigger avoidance is insufficient, the use of medication is recommended. Pharmaceutical drugs are selected based on, among other things, the severity of illness and the frequency of symptoms. Specific medications for asthma are broadly classified into fast-acting and long-acting categories.[157][158] The medications listed below have demonstrated efficacy in improving asthma symptoms; however, real world use-effectiveness is limited as around half of people with asthma worldwide remain sub-optimally controlled, even when treated.[159][160][161] People with asthma may remain sub-optimally controlled either because optimum doses of asthma medications do not work (called "refractory" asthma) or because individuals are either unable (e.g. inability to afford treatment, poor inhaler technique) or unwilling (e.g., wish to avoid side effects of corticosteroids) to take optimum doses of prescribed asthma medications (called "difficult to treat" asthma). In practice, it is not possible to distinguish "refractory" from "difficult to treat" categories for patients who have never taken optimum doses of asthma medications. A related issue is that the asthma efficacy trials upon which the pharmacological treatment guidelines are based have systematically excluded the majority of people with asthma.[162][163] For example, asthma efficacy treatment trials always exclude otherwise eligible people who smoke, and smoking diminishes the efficacy of inhaled corticosteroids, the mainstay of asthma control management.[164][165][166]

Bronchodilators are recommended for short-term relief of symptoms. In those with occasional attacks, no other medication is needed. If mild persistent disease is present (more than two attacks a week), low-dose inhaled corticosteroids or alternatively, a leukotriene antagonist or a mast cell stabilizer by mouth is recommended. For those who have daily attacks, a higher dose of inhaled corticosteroids is used. In a moderate or severe exacerbation, corticosteroids by mouth are added to these treatments.[8]

People with asthma have higher rates of anxiety, psychological stress, and depression.[167][168] This is associated with poorer asthma control.[167] Cognitive behavioral therapy may improve quality of life, asthma control, and anxiety levels in people with asthma.[167]

Improving people's knowledge about asthma and using a written action plan has been identified as an important component of managing asthma.[169] Providing educational sessions that include information specific to a person's culture is likely effective.[170] More research is necessary to determine if increasing preparedness and knowledge of asthma among school staff and families using home-based and school interventions results in long term improvements in safety for children with asthma.[171][172][173] School-based asthma self-management interventions, which attempt to improve knowledge of asthma, its triggers and the importance of regular practitioner review, may reduce hospital admissions and emergency department visits. These interventions may also reduce the number of days children experience asthma symptoms and may lead to small improvements in asthma-related quality of life.[174] More research is necessary to determine if shared-decision-making is helpful for managing adults with asthma[175] or if a personalized asthma action plan is effective and necessary.[176] Some people with asthma use pulse oximeters to monitor their own blood oxygen levels during an asthma attack. However, there is no evidence regarding the use in these instances.[177]

Lifestyle modification

Avoidance of triggers is a key component of improving control and preventing attacks. The most common triggers include allergens, smoke (from tobacco or other sources), air pollution, nonselective beta-blockers, and sulfite-containing foods.[178][179] Cigarette smoking and second-hand smoke (passive smoke) may reduce the effectiveness of medications such as corticosteroids.[180] Laws that limit smoking decrease the number of people hospitalized for asthma.[155] Dust mite control measures, including air filtration, chemicals to kill mites, vacuuming, mattress covers and others methods had no effect on asthma symptoms.[64] There is insufficient evidence to suggest that dehumidifiers are helpful for controlling asthma.[181]

Overall, exercise is beneficial in people with stable asthma.[182] Yoga could provide small improvements in quality of life and symptoms in people with asthma.[183] More research is necessary to determine how effective weight loss is on improving quality of life, the usage of health care services, and adverse effects for people of all ages with asthma.[184][185]

Medications

Medications used to treat asthma are divided into two general classes: quick-relief medications used to treat acute symptoms; and long-term control medications used to prevent further exacerbation.[157] Antibiotics are generally not needed for sudden worsening of symptoms or for treating asthma at any time.[186][187]

Medications for asthma exacerbations

 
Salbutamol metered dose inhaler commonly used to treat asthma attacks
  • Short-acting beta2-adrenoceptor agonists (SABA), such as salbutamol (albuterol USAN) are the first line treatment for asthma symptoms.[8] They are recommended before exercise in those with exercise induced symptoms.[188]
  • Anticholinergic medications, such as ipratropium, provide additional benefit when used in combination with SABA in those with moderate or severe symptoms and may prevent hospitalizations.[8][189][190] Anticholinergic bronchodilators can also be used if a person cannot tolerate a SABA.[105] If a child requires admission to hospital additional ipratropium does not appear to help over a SABA.[191] For children over 2 years old with acute asthma symptoms, inhaled anticholinergic medications taken alone is safe but is not as effective as inhaled SABA or SABA combined with inhaled anticholinergic medication.[192][189] Adults who receive combined inhaled medications that includes short-acting anticholinergics and SABA may be at risk for increased adverse effects such as experiencing a tremor, agitation, and heart beat palpitations compared to people who are treated with SABA by itself.[190]
  • Older, less selective adrenergic agonists, such as inhaled epinephrine, have similar efficacy to SABAs.[193] They are however not recommended due to concerns regarding excessive cardiac stimulation.[194]
  • Corticosteroids can also help with the acute phase of an exacerbation because of their antiinflamatory properties. The benefit of systemic and oral corticosteroids is well established. Inhaled or nebulized corticosteroids can also be used.[152] For adults and children who are in the hospital due to acute asthma, systemic (IV) corticosteroids improve symptoms.[195][196] A short course of corticosteroids after an acute asthma exacerbation may help prevent relapses and reduce hospitalizations.[197]
  • Other remedies, less established, are intravenous or nebulized magnesium sulfate and helium mixed with oxygen. Aminophylline could be used with caution as well.[152]
  • Mechanical ventilation is the last resort in case of severe hypoxemia.[152]
  • Intravenous administration of the drug aminophylline does not provide an improvement in bronchodilation when compared to standard inhaled beta-2 agonist treatment.[198] Aminophylline treatment is associated with more adverse effects compared to inhaled beta-2 agonist treatment.[198]

Long–term control

 
Fluticasone propionate metered dose inhaler commonly used for long-term control
  • Corticosteroids are generally considered the most effective treatment available for long-term control.[157] Inhaled forms are usually used except in the case of severe persistent disease, in which oral corticosteroids may be needed.[157] Dosage depends on the severity of symptoms.[199] High dosage and long term use might lead to the appearance of common adverse effects which are growth delay, adrenal suppression, and osteoporosis.[152] Continuous (daily) use of an inhaled corticosteroid, rather than its intermitted use, seems to provide better results in controlling asthma exacerbations.[152] Commonly used corticosteroids are budesonide, fluticasone, mometasone and ciclesonide.[152]
  • Long-acting beta-adrenoceptor agonists (LABA) such as salmeterol and formoterol can improve asthma control, at least in adults, when given in combination with inhaled corticosteroids.[200][201] In children this benefit is uncertain.[200][202][201] When used without steroids they increase the risk of severe side-effects,[203] and with corticosteroids they may slightly increase the risk.[204][205] Evidence suggests that for children who have persistent asthma, a treatment regime that includes LABA added to inhaled corticosteroids may improve lung function but does not reduce the amount of serious exacerbations.[206] Children who require LABA as part of their asthma treatment may need to go to the hospital more frequently.[206]
  • Leukotriene receptor antagonists (anti-leukotriene agents such as montelukast and zafirlukast) may be used in addition to inhaled corticosteroids, typically also in conjunction with a LABA.[17][207][208][209] For adults or adolescents who have persistent asthma that is not controlled very well, the addition of anti-leukotriene agents along with daily inhaled corticosteriods improves lung function and reduces the risk of moderate and severe asthma exacerbations.[208] Anti-leukotriene agents may be effective alone for adolescents and adults; however, there is no clear research suggesting which people with asthma would benefit from anti-leukotriene receptor alone.[210] In those under five years of age, anti-leukotriene agents were the preferred add-on therapy after inhaled corticosteroids.[152][211] A 2013 Cochrane systematic review concluded that anti-leukotriene agents appear to be of little benefit when added to inhaled steroids for treating children.[212] A similar class of drugs, 5-LOX inhibitors, may be used as an alternative in the chronic treatment of mild to moderate asthma among older children and adults.[17][213] As of 2013 there is one medication in this family known as zileuton.[17]
  • Mast cell stabilizers (such as cromolyn sodium) are safe alternatives to corticosteroids but not preferred because they have to be administered frequently.[157][17]
  • Oral Theophyllines are sometimes used for controlling chronic asthma, but their used is minimized because of their side effects.[152]
  • Omalizumab, a monoclonal Antibody Against IgE, is a novel way to lessen exacerbations by decreasing the levels of circulating IgE that play a significant role at allergic asthma.[152][214]
  • Anticholinergic medications such as ipratropium bromide have not been shown to be beneficial for treating chronic asthma in children over 2 years old,[215] but is not suggested for routine treatment of chronic asthma in adults.[216]
  • There is no strong evidence to recommend chloroquine medication as a replacement for taking corticosteroids by mouth (for those who are not able to tolerate inhaled steroids).[217] Methotrexate is not suggested as a replacement for taking corticosteriods by mouth ("steroid sparing") due to the adverse effects associated with taking methotrexate and the minimal relief provided for asthma symptoms.[218]
  • Macrolide antibiotics, particularly the azalide macrolide azithromycin, are a recently added GINA-recommended treatment option for both eosinophilic and non-eosinophilic severe, refractory asthma based on azithromycin's efficacy in reducing moderate and severe exacerbations combined.[219][220] Azithromycin's mechanism of action is not established, and could involve pathogen- and/or host-directed anti-inflammatory activities.[221] Limited clinical observations suggest that some patients with new-onset asthma and with "difficult-to-treat" asthma (including those with the asthma-COPD overlap syndrome - ACOS) may respond dramatically to azithromycin.[222][223] However, these groups of asthma patients have not been studied in randomized treatment trials and patient selection needs to be carefully individualized.

For children with asthma which is well-controlled on combination therapy of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA), the benefits and harms of stopping LABA and stepping down to ICS-only therapy are uncertain.[224] In adults who have stable asthma while they are taking a combination of LABA and inhaled corticosteroids (ICS), stopping LABA may increase the risk of asthma exacerbations that require treatment with corticosteroids by mouth.[225] Stopping LABA probably makes little or no important difference to asthma control or asthma-related quality of life.[225] Whether or not stopping LABA increases the risk of serious adverse events or exacerbations requiring an emergency department visit or hospitalisation is uncertain.[225]

Delivery methods

Medications are typically provided as metered-dose inhalers (MDIs) in combination with an asthma spacer or as a dry powder inhaler. The spacer is a plastic cylinder that mixes the medication with air, making it easier to receive a full dose of the drug. A nebulizer may also be used. Nebulizers and spacers are equally effective in those with mild to moderate symptoms. However, insufficient evidence is available to determine whether a difference exists in those with severe disease.[226] For delivering short-acting beta-agonists in acute asthma in children, spacers may have advantages compared to nebulisers, but children with life-threatening asthma have not been studied.[227] There is no strong evidence for the use of intravenous LABA for adults or children who have acute asthma.[228] There is insufficient evidence to directly compare the effectiveness of a metered-dose inhaler attached to a homemade spacer compared to commercially available spacer for treating children with asthma.[229]

Adverse effects

Long-term use of inhaled corticosteroids at conventional doses carries a minor risk of adverse effects.[230] Risks include thrush, the development of cataracts, and a slightly slowed rate of growth.[230][231][232] Rinsing the mouth after the use of inhaled steroids can decrease the risk of thrush.[233] Higher doses of inhaled steroids may result in lower bone mineral density.[234]

Others

Inflammation in the lungs can be estimated by the level of exhaled nitric oxide.[235][236] The use of exhaled nitric oxide levels (FeNO) to guide asthma medication dosing may have small benefits for preventing asthma attacks but the potential benefits are not strong enough for this approach to be universally recommended as a method to guide asthma therapy in adults or children.[235][236]

When asthma is unresponsive to usual medications, other options are available for both emergency management and prevention of flareups. Additional options include:

  • Humidified oxygen to alleviate hypoxia if saturations fall below 92%.[152]
  • Corticosteroid by mouth are recommended with five days of prednisone being the same 2 days of dexamethasone.[237] One review recommended a seven-day course of steroids.[238]
  • Magnesium sulfate intravenous treatment increases bronchodilation when used in addition to other treatment in moderate severe acute asthma attacks.[18][239][240] In adults intravenous treatment results in a reduction of hospital admissions.[241] Low levels of evidence suggest that inhaled (nebulised) magnesium sulfate may have a small benefit for treating acute asthma in adults.[242] Overall, high quality evidence do not indicate a large benefit for combining magnesium sulfate with standard inhaled treatments for adults with asthma.[242]
  • Heliox, a mixture of helium and oxygen, may also be considered in severe unresponsive cases.[18]
  • Intravenous salbutamol is not supported by available evidence and is thus used only in extreme cases.[243]
  • Methylxanthines (such as theophylline) were once widely used, but do not add significantly to the effects of inhaled beta-agonists.[243] Their use in acute exacerbations is controversial.[244]
  • The dissociative anesthetic ketamine is theoretically useful if intubation and mechanical ventilation is needed in people who are approaching respiratory arrest; however, there is no evidence from clinical trials to support this.[245] A 2012 Cochrane review found no significant benefit from the use of ketamine in severe acute asthma in children.[246]
  • For those with severe persistent asthma not controlled by inhaled corticosteroids and LABAs, bronchial thermoplasty may be an option.[247] It involves the delivery of controlled thermal energy to the airway wall during a series of bronchoscopies.[247][248] While it may increase exacerbation frequency in the first few months it appears to decrease the subsequent rate. Effects beyond one year are unknown.[249]
  • Monoclonal antibody injections such as mepolizumab,[250] dupilumab,[251] or omalizumab may be useful in those with poorly controlled atopic asthma.[252] However, as of 2019 these medications are expensive and their use is therefore reserved for those with severe symptoms to achieve cost-effectiveness.[253] Monoclonal antibodies targeting interleukin-5 (IL-5) or its receptor (IL-5R), including mepolizumab, reslizumab or benralizumab, in addition to standard care in severe asthma is effective in reducing the rate of asthma exacerbations. There is limited evidence for improved health-related quality of life and lung function.[254]
  • Evidence suggests that sublingual immunotherapy in those with both allergic rhinitis and asthma improve outcomes.[255]
  • It is unclear if non-invasive positive pressure ventilation in children is of use as it has not been sufficiently studied.[256]

Adherence to asthma treatments

Staying with a treatment approach for preventing asthma exacerbations can be challenging, especially if the person is required to take medicine or treatments daily.[257] Reasons for low adherence range from a conscious decision to not follow the suggested medical treatment regime for various reasons including avoiding potential side effects, misinformation, or other beliefs about the medication.[257] Problems accessing the treatment and problems administering the treatment effectively can also result in lower adherence. Various approaches have been undertaken to try and improve adherence to treatments to help people prevent serious asthma exacerbations including digital interventions.[257]

Alternative medicine

Many people with asthma, like those with other chronic disorders, use alternative treatments; surveys show that roughly 50% use some form of unconventional therapy.[258][259] There is little data to support the effectiveness of most of these therapies.

Evidence is insufficient to support the usage of vitamin C or vitamin E for controlling asthma.[260][261] There is tentative support for use of vitamin C in exercise induced bronchospasm.[262] Fish oil dietary supplements (marine n-3 fatty acids)[263] and reducing dietary sodium[264] do not appear to help improve asthma control. In people with mild to moderate asthma, treatment with vitamin D supplementation or its hydroxylated metabolites does not reduce acute exacerbations or improve control.[265] There is no strong evidence to suggest that vitamin D supplements improve day-to-day asthma symptoms or a person's lung function.[265] There is no strong evidence to suggest that adults with asthma should avoid foods that contain monosodium glutamate (MSG).[266] There have not been enough high-quality studies performed to determine if children with asthma should avoid eating food that contains MSG.[266]

Acupuncture is not recommended for the treatment as there is insufficient evidence to support its use.[267][268] Air ionisers show no evidence that they improve asthma symptoms or benefit lung function; this applied equally to positive and negative ion generators.[269] Manual therapies, including osteopathic, chiropractic, physiotherapeutic and respiratory therapeutic maneuvers, have insufficient evidence to support their use in treating asthma.[270] Pulmonary rehabilitation, however, may improve quality of life and functional exercise capacity when compared to usual care for adults with asthma.[271] The Buteyko breathing technique for controlling hyperventilation may result in a reduction in medication use; however, the technique does not have any effect on lung function.[158] Thus an expert panel felt that evidence was insufficient to support its use.[267] There is no clear evidence that breathing exercises are effective for treating children with asthma.[272]

Prognosis

The prognosis for asthma is generally good, especially for children with mild disease.[273] Mortality has decreased over the last few decades due to better recognition and improvement in care.[274] In 2010 the death rate was 170 per million for males and 90 per million for females.[275] Rates vary between countries by 100-fold.[275]

Globally it causes moderate or severe disability in 19.4 million people as of 2004 (16 million of which are in low and middle income countries).[276] Of asthma diagnosed during childhood, half of cases will no longer carry the diagnosis after a decade.[77] Airway remodeling is observed, but it is unknown whether these represent harmful or beneficial changes.[277] More recent data find that severe asthma can result in airway remodeling and the "asthma with chronic obstructive pulmonary disease syndrome (ACOS)" that has a poor prognosis.[278] Early treatment with corticosteroids seems to prevent or ameliorates a decline in lung function.[279] Asthma in children also has negative effects on quality of life of their parents.[280]

  •  
    Asthma deaths per million persons in 2012
      0–10
      11–13
      14–17
      18–23
      24–32
      33–43
      44–50
      51–66
      67–95
      96–251
  •  
    Disability-adjusted life year for asthma per 100,000 inhabitants in 2004[281]
      no data
      0-100
      100–150
      150–200
      200–250
      250–300
      300–350
      350–400
      400–450
      450–500
      500–550
      550–600
      >600

Epidemiology

Main article: Epidemiology of asthma
 
Rates of asthma in 2017[282]

In 2019, approximately 262 million people worldwide were affected by asthma and approximately 461,000 people died from the disease.[9] Rates vary between countries with prevalences between 1 and 18%.[22] It is more common in developed than developing countries.[22] One thus sees lower rates in Asia, Eastern Europe and Africa.[21] Within developed countries it is more common in those who are economically disadvantaged while in contrast in developing countries it is more common in the affluent.[22] The reason for these differences is not well known.[22] Low and middle income countries make up more than 80% of the mortality.[283]

While asthma is twice as common in boys as girls,[22] severe asthma occurs at equal rates.[284] In contrast adult women have a higher rate of asthma than men[22] and it is more common in the young than the old.[21] In 2010, children with asthma experienced over 900,000 emergency department visits, making it the most common reason for admission to the hospital following an emergency department visit in the US in 2011.[285][286]

Global rates of asthma have increased significantly between the 1960s and 2008[19][287] with it being recognized as a major public health problem since the 1970s.[21] Rates of asthma have plateaued in the developed world since the mid-1990s with recent increases primarily in the developing world.[288] Asthma affects approximately 7% of the population of the United States[203] and 5% of people in the United Kingdom.[289] Canada, Australia and New Zealand have rates of about 14–15%.[290]

The average death rate from 2011 to 2015 from asthma in the UK was about 50% higher than the average for the European Union and had increased by about 5% in that time.[291] Children are more likely see a physician due to asthma symptoms after school starts in September.[292]

Population-based epidemiological studies describe temporal associations between acute respiratory illnesses, asthma, and development of severe asthma with irreversible airflow limitation (known as the asthma-chronic obstructive pulmonary disease "overlap" syndrome, or ACOS).[293][294][295] Additional prospective population-based data indicate that ACOS seems to represent a form of severe asthma, characterised by more frequent hospitalisations, and to be the result of early-onset asthma that has progressed to fixed airflow obstruction.[296]

Economics

From 2000 to 2010, the average cost per asthma-related hospital stay in the United States for children remained relatively stable at about $3,600, whereas the average cost per asthma-related hospital stay for adults increased from $5,200 to $6,600.[297] In 2010, Medicaid was the most frequent primary payer among children and adults aged 18–44 years in the United States; private insurance was the second most frequent payer.[297] Among both children and adults in the lowest income communities in the United States there is a higher rate of hospital stays for asthma in 2010 than those in the highest income communities.[297]

History

 
Ebers Papyrus detailing treatment of asthma
 
1907 advertisement for Grimault's Indian Cigarettes, promoted as a means of relieving asthma. They contained belladonna and cannabis.
 
The Gold-dust Book of Cold Damage dated '1st year of the Zhengyuan reign period of the Yuan dynasty' (1341) Wellcome.

Asthma was recognized in ancient Egypt and was treated by drinking an incense mixture known as kyphi.[20] It was officially named as a specific respiratory problem by Hippocrates circa 450 BC, with the Greek word for "panting" forming the basis of our modern name.[21] In 200 BC it was believed to be at least partly related to the emotions.[29] In the 12th century the Jewish physician-philosopher Maimonides wrote a treatise on asthma in Arabic, based partly on Arabic sources, in which he discussed the symptoms, proposed various dietary and other means of treatment, and emphasized the importance of climate and clean air.[298] Chinese Traditional Medicine also offered medication for asthma, as indicated by a surviving 14th century manuscript curated by the Wellcome Foundation.[299]

In 1873, one of the first papers in modern medicine on the subject tried to explain the pathophysiology of the disease while one in 1872, concluded that asthma can be cured by rubbing the chest with chloroform liniment.[300][301] Medical treatment in 1880 included the use of intravenous doses of a drug called pilocarpine.[302] In 1886, F. H. Bosworth theorized a connection between asthma and hay fever.[303] Epinephrine was first referred to in the treatment of asthma in 1905.[304] Oral corticosteroids began to be used for this condition in the 1950s while inhaled corticosteroids and selective short acting beta agonist came into wide use in the 1960s.[305][306]

A well-documented case in the 19th century was that of young Theodore Roosevelt (1858–1919). At that time there was no effective treatment. Roosevelt's youth was in large part shaped by his poor health partly related to his asthma. He experienced recurring nighttime asthma attacks that felt as if he was being smothered to death, terrifying the boy and his parents.[307]

During the 1930s to 1950s, asthma was known as one of the "holy seven" psychosomatic illnesses. Its cause was considered to be psychological, with treatment often based on psychoanalysis and other talking cures.[308] As these psychoanalysts interpreted the asthmatic wheeze as the suppressed cry of the child for its mother, they considered the treatment of depression to be especially important for individuals with asthma.[308]

In January 2021, an appeal court in France overturned a deportation order against a 40-year-old Bangladeshi man, who was a patient of asthma. His lawyers had argued that the dangerous levels of pollution in Bangladesh could possibly lead to worsening of his health condition, or even premature death.[309]

Notes

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February 15, 2024
asthma, other, uses, disambiguation, confused, with, ahimsa, long, term, inflammatory, disease, airways, lungs, characterized, variable, recurring, symptoms, reversible, airflow, obstruction, easily, triggered, bronchospasms, symptoms, include, episodes, wheez. For other uses see Asthma disambiguation Not to be confused with Ahimsa Asthma is a long term inflammatory disease of the airways of the lungs 5 It is characterized by variable and recurring symptoms reversible airflow obstruction and easily triggered bronchospasms 10 11 Symptoms include episodes of wheezing coughing chest tightness and shortness of breath 4 These may occur a few times a day or a few times per week 5 Depending on the person asthma symptoms may become worse at night or with exercise 5 AsthmaPeak flow meters are used to measure the peak expiratory flow rate important in both monitoring and diagnosing asthma 1 PronunciationUK ˈ ae s m e ˈ ae s 8 m e US ˈ ae z m e 2 3 SpecialtyPulmonologySymptomsRecurring episodes of wheezing coughing chest tightness shortness of breath 4 ComplicationsGastroesophageal reflux disease GERD sinusitis obstructive sleep apneaUsual onsetChildhoodDurationLong term 5 CausesGenetic and environmental factors 4 Risk factorsAir pollution allergens 5 Diagnostic methodBased on symptoms response to therapy spirometry 6 TreatmentAvoiding triggers inhaled corticosteroids salbutamol 7 8 Frequencyapprox 262 million 2019 9 Deathsapprox 461 000 2019 9 Asthma is thought to be caused by a combination of genetic and environmental factors 4 Environmental factors include exposure to air pollution and allergens 5 Other potential triggers include medications such as aspirin and beta blockers 5 Diagnosis is usually based on the pattern of symptoms response to therapy over time and spirometry lung function testing 6 Asthma is classified according to the frequency of symptoms forced expiratory volume in one second FEV1 and peak expiratory flow rate 12 It may also be classified as atopic or non atopic where atopy refers to a predisposition toward developing a type 1 hypersensitivity reaction 13 14 There is no known cure for asthma but it can be controlled 5 Symptoms can be prevented by avoiding triggers such as allergens and respiratory irritants and suppressed with the use of inhaled corticosteroids 7 15 Long acting beta agonists LABA or antileukotriene agents may be used in addition to inhaled corticosteroids if asthma symptoms remain uncontrolled 16 17 Treatment of rapidly worsening symptoms is usually with an inhaled short acting beta2 agonist such as salbutamol and corticosteroids taken by mouth 8 In very severe cases intravenous corticosteroids magnesium sulfate and hospitalization may be required 18 In 2019 asthma affected approximately 262 million people and caused approximately 461 000 deaths 9 Most of the deaths occurred in the developing world 5 Asthma often begins in childhood 5 and the rates have increased significantly since the 1960s 19 Asthma was recognized as early as Ancient Egypt 20 The word asthma is from the Greek ἆs8ma asthma which means panting 21 Contents 1 Signs and symptoms 1 1 Associated conditions 2 Causes 2 1 Environmental 2 1 1 Hygiene hypothesis 2 2 Genetic 2 3 Medical conditions 2 4 Exacerbation 3 Pathophysiology 4 Diagnosis 4 1 Spirometry 4 2 Others 4 3 Classification 4 3 1 Asthma exacerbation 4 3 2 Exercise induced 4 3 3 Occupational 4 3 4 Aspirin exacerbated respiratory disease 4 3 5 Alcohol induced asthma 4 3 6 Non atopic asthma 4 3 7 Infectious asthma 4 3 8 Phenotyping and endotyping 4 4 Differential diagnosis 5 Prevention 6 Management 6 1 Lifestyle modification 6 2 Medications 6 2 1 Medications for asthma exacerbations 6 2 2 Long term control 6 2 3 Delivery methods 6 2 4 Adverse effects 6 3 Others 6 4 Adherence to asthma treatments 6 5 Alternative medicine 7 Prognosis 8 Epidemiology 9 Economics 10 History 11 Notes 12 References 13 External linksSigns and symptoms nbsp Wheezing source source The sound of wheezing as heard with a stethoscope Problems playing this file See media help Asthma is characterized by recurrent episodes of wheezing shortness of breath chest tightness and coughing 22 Sputum may be produced from the lung by coughing but is often hard to bring up 23 During recovery from an asthma attack exacerbation it may appear pus like due to high levels of white blood cells called eosinophils 24 Symptoms are usually worse at night and in the early morning or in response to exercise or cold air 25 Some people with asthma rarely experience symptoms usually in response to triggers whereas others may react frequently and readily and experience persistent symptoms 26 Associated conditions A number of other health conditions occur more frequently in people with asthma including gastroesophageal reflux disease GERD rhinosinusitis and obstructive sleep apnea 27 Psychological disorders are also more common 28 with anxiety disorders occurring in between 16 and 52 and mood disorders in 14 41 29 It is not known whether asthma causes psychological problems or psychological problems lead to asthma 30 Current asthma but not former asthma is associated with increased all cause mortality heart disease mortality and chronic lower respiratory tract disease mortality 31 Asthma particularly severe asthma is strongly associated with development of chronic obstructive pulmonary disease COPD 32 33 34 Those with asthma especially if it is poorly controlled are at increased risk for radiocontrast reactions 35 Cavities occur more often in people with asthma 36 This may be related to the effect of beta2 agonists decreasing saliva 37 These medications may also increase the risk of dental erosions 37 CausesAsthma is caused by a combination of complex and incompletely understood environmental and genetic interactions 38 39 These influence both its severity and its responsiveness to treatment 40 It is believed that the recent increased rates of asthma are due to changing epigenetics heritable factors other than those related to the DNA sequence and a changing living environment 41 Asthma that starts before the age of 12 years old is more likely due to genetic influence while onset after age 12 is more likely due to environmental influence 42 Environmental See also Asthma related microbes Many environmental factors have been associated with asthma s development and exacerbation including allergens air pollution and other environmental chemicals 43 There are some substances that are known to cause asthma in exposed people and they are called asthmagens Some common asthmagens include ammonia latex pesticides solder and welding fumes metal or wood dusts spraying of isocyanate paint in vehicle repair formaldehyde glutaraldehyde anhydrides glues dyes metal working fluids oil mists molds 44 45 Smoking during pregnancy and after delivery is associated with a greater risk of asthma like symptoms 46 Low air quality from environmental factors such as traffic pollution or high ozone levels 47 has been associated with both asthma development and increased asthma severity 48 Over half of cases in children in the United States occur in areas when air quality is below the EPA standards 49 Low air quality is more common in low income and minority communities 50 Exposure to indoor volatile organic compounds may be a trigger for asthma formaldehyde exposure for example has a positive association 51 Phthalates in certain types of PVC are associated with asthma in both children and adults 52 53 While exposure to pesticides is linked to the development of asthma a cause and effect relationship has yet to be established 54 55 A meta analysis concluded gas stoves are a major risk factor for asthma finding around one in eight cases in the U S could be attributed to these 56 The majority of the evidence does not support a causal role between paracetamol acetaminophen or antibiotic use and asthma 57 58 A 2014 systematic review found that the association between paracetamol use and asthma disappeared when respiratory infections were taken into account 59 Maternal psychological stress during pregnancy is a risk factor for the child to develop asthma 60 Asthma is associated with exposure to indoor allergens 61 Common indoor allergens include dust mites cockroaches animal dander fragments of fur or feathers and mold 62 63 Efforts to decrease dust mites have been found to be ineffective on symptoms in sensitized subjects 64 65 Weak evidence suggests that efforts to decrease mold by repairing buildings may help improve asthma symptoms in adults 66 Certain viral respiratory infections such as respiratory syncytial virus and rhinovirus 21 may increase the risk of developing asthma when acquired as young children 67 Certain other infections however may decrease the risk 21 Hygiene hypothesis The hygiene hypothesis attempts to explain the increased rates of asthma worldwide as a direct and unintended result of reduced exposure during childhood to non pathogenic bacteria and viruses 68 69 It has been proposed that the reduced exposure to bacteria and viruses is due in part to increased cleanliness and decreased family size in modern societies 70 Exposure to bacterial endotoxin in early childhood may prevent the development of asthma but exposure at an older age may provoke bronchoconstriction 71 Evidence supporting the hygiene hypothesis includes lower rates of asthma on farms and in households with pets 70 Use of antibiotics in early life has been linked to the development of asthma 72 Also delivery via caesarean section is associated with an increased risk estimated at 20 80 of asthma this increased risk is attributed to the lack of healthy bacterial colonization that the newborn would have acquired from passage through the birth canal 73 74 There is a link between asthma and the degree of affluence which may be related to the hygiene hypothesis as less affluent individuals often have more exposure to bacteria and viruses 75 Genetic CD14 endotoxin interaction based on CD14 SNP C 159T 76 Endotoxin levels CC genotype TT genotypeHigh exposure Low risk High riskLow exposure High risk Low riskFamily history is a risk factor for asthma with many different genes being implicated 77 If one identical twin is affected the probability of the other having the disease is approximately 25 77 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 78 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 78 In 2006 over 100 genes were associated with asthma in one genetic association study alone 78 more continue to be found 79 Some genetic variants may only cause asthma when they are combined with specific environmental exposures 38 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 76 Medical conditions A triad of atopic eczema allergic rhinitis and asthma is called atopy 80 The strongest risk factor for developing asthma is a history of atopic disease 67 with asthma occurring at a much greater rate in those who have either eczema or hay fever 81 Asthma has been associated with eosinophilic granulomatosis with polyangiitis formerly known as Churg Strauss syndrome an autoimmune disease and vasculitis 82 Individuals with certain types of urticaria may also experience symptoms of asthma 80 There is a correlation between obesity and the risk of asthma with both having increased in recent years 83 84 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 85 Beta blocker medications such as propranolol can trigger asthma in those who are susceptible 86 Cardioselective beta blockers however appear safe in those with mild or moderate disease 87 88 Other medications that can cause problems in asthmatics are angiotensin converting enzyme inhibitors aspirin and NSAIDs 89 Use of acid suppressing medication proton pump inhibitors and H2 blockers during pregnancy is associated with an increased risk of asthma in the child 90 Exacerbation Some individuals will have stable asthma for weeks or months and then suddenly develop an episode of acute asthma Different individuals react to various factors in different ways 91 Most individuals can develop severe exacerbation from a number of triggering agents 91 Home factors that can lead to exacerbation of asthma include dust animal dander especially cat and dog hair cockroach allergens and mold 91 92 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 91 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 48 93 Asthma exacerbations in school aged children peak in autumn shortly after children return to school This might reflect a combination of factors including poor treatment adherence increased allergen and viral exposure and altered immune tolerance There is limited evidence to guide possible approaches to reducing autumn exacerbations but while costly seasonal omalizumab treatment from four to six weeks before school return may reduce autumn asthma exacerbations 94 PathophysiologyMain article Pathophysiology of asthma nbsp Figure A shows the location of the lungs and airways in the body Figure B shows a cross section of a normal airway Figure C shows a cross section of an airway during asthma symptoms nbsp Obstruction of the lumen of a bronchiole by mucoid exudate goblet cell metaplasia and epithelial basement membrane thickening in a person with asthma nbsp Diagram of asthma Asthma is the result of chronic inflammation of the conducting zone of the airways most especially the bronchi and bronchioles which subsequently results in increased contractability of the surrounding smooth 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 22 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 and neutrophils There may also be involvement of other components of the immune system including cytokines chemokines histamine and leukotrienes among others 21 DiagnosisWhile asthma is a well recognized condition there is not one universal agreed upon definition 21 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 22 There is currently no precise test for the diagnosis which is typically based on the pattern of symptoms and response to therapy over time 6 21 Asthma may 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 95 Spirometry is then used to confirm the diagnosis 95 In children under the age of six the diagnosis is more difficult as they are too young for spirometry 96 Spirometry Spirometry is recommended to aid in diagnosis and management 97 98 It is the single best test for asthma If the FEV1 measured by this technique improves more than 12 and increases by at least 200 milliliters following administration of a bronchodilator such as salbutamol this is supportive of the diagnosis It however may be normal in those with a history of mild asthma not currently acting up 21 As caffeine is a bronchodilator in people with asthma the use of caffeine before a lung function test may interfere with the results 99 Single breath diffusing capacity can help differentiate asthma from COPD 21 It is reasonable to perform spirometry every one or two years to follow how well a person s asthma is controlled 100 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 21 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 101 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 102 Classification Clinical classification 12 years old 12 Severity Symptom frequency Night time symptoms FEV1 of predicted FEV1 variability SABA useIntermittent 2 week 2 month 80 lt 20 2 days weekMild persistent gt 2 week 3 4 month 80 20 30 gt 2 days weekModerate persistent Daily gt 1 week 60 80 gt 30 dailySevere persistent Continuously Frequent 7 week lt 60 gt 30 twice dayAsthma is clinically classified according to the frequency of symptoms forced expiratory volume in one second FEV1 and peak expiratory flow rate 12 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 13 While asthma is classified based on severity at the moment there is no clear method for classifying different subgroups of asthma beyond this system 103 Finding ways to identify subgroups that respond well to different types of treatments is a current critical goal of asthma research 103 Recently asthma has been classified based on whether it is associated with type 2 or non type 2 inflammation This approach to immunologic classification is driven by a developing understanding of the underlying immune processes and by the development of therapeutic approaches that target type 2 inflammation 104 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 and emphysema 105 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 106 In contrast to emphysema asthma affects the bronchi not the alveoli 107 The combination of asthma with a component of irreversible airway obstruction has been termed the asthma chronic obstructive disease COPD overlap syndrome ACOS Compared to other people with pure asthma or COPD people with ACOS exhibit increased morbidity mortality and possibly more comorbidities 108 Asthma exacerbation Severity of an acute exacerbation 109 Near fatal High PaCO2 or requiring mechanical ventilation or bothLife threatening any one of Clinical signs MeasurementsAltered level of consciousness Peak flow lt 33 Exhaustion Oxygen saturation lt 92 Arrhythmia PaO2 lt 8 kPaLow blood pressure Normal PaCO2CyanosisSilent chestPoor respiratory effortAcute severe any one of Peak flow 33 50 Respiratory rate 25 breaths per minuteHeart rate 110 beats per minuteUnable to complete sentences in one breathModerate Worsening symptomsPeak flow 50 80 best or predictedNo features of acute severe asthmaAn acute asthma exacerbation is commonly referred to as an asthma attack The classic symptoms are shortness of breath wheezing and chest tightness 21 The wheezing is most often when breathing out 110 While these are the primary symptoms of asthma 111 some people present primarily with coughing and in severe cases air motion may be significantly impaired such that no wheezing is heard 109 In children chest pain is often present 112 Signs occurring 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 113 A blue color of the skin and nails may occur from lack of oxygen 114 In a mild exacerbation the peak expiratory flow rate PEFR is 200 L min or 50 of the predicted best 115 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 115 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 116 Half of cases are due to infections with others caused by allergen air pollution or insufficient or inappropriate medication use 116 Brittle asthma is a kind of asthma distinguishable by recurrent severe attacks 109 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 109 Exercise induced Main article Exercise induced bronchoconstriction Exercise can trigger bronchoconstriction both in people with or without asthma 117 It occurs in most people with asthma and up to 20 of people without asthma 117 Exercise induced bronchoconstriction is common in professional athletes The highest rates are among cyclists up to 45 swimmers and cross country skiers 118 While it may occur with any weather conditions it is more common when it is dry and cold 119 Inhaled beta2 agonists do not appear to improve athletic performance among those without asthma 120 however oral doses may improve endurance and strength 121 122 Occupational Main article Occupational asthma Asthma as a result of or worsened by workplace exposures is a commonly reported occupational disease 123 Many cases however are not reported or recognized as such 124 125 It is estimated that 5 25 of asthma cases in adults are work related A few hundred different agents have been implicated with the most common being isocyanates grain and wood dust colophony soldering flux latex animals and aldehydes The employment associated with the highest risk of problems include those who spray paint bakers and those who process food nurses chemical workers those who work with animals welders hairdressers and timber workers 123 Aspirin exacerbated respiratory disease Main article Aspirin exacerbated respiratory disease Aspirin exacerbated respiratory disease AERD also known as aspirin induced asthma affects up to 9 of asthmatics 126 AERD consists of asthma nasal polyps sinus disease and respiratory reactions to aspirin and other NSAID medications such as ibuprofen and naproxen 127 People often also develop loss of smell and most experience respiratory reactions to alcohol 128 Alcohol induced asthma Main article Alcohol induced respiratory reactions Alcohol may worsen asthmatic symptoms in up to a third of people 129 This may be even more common in some ethnic groups such as the Japanese and those with aspirin exacerbated respiratory disease 129 Other studies have found improvement in asthmatic symptoms from alcohol 129 Non atopic asthma Non atopic asthma also known as intrinsic or non allergic makes up between 10 and 33 of cases There is negative skin test to common inhalant allergens Often it starts later in life and women are more commonly affected than men Usual treatments may not work as well 130 The concept that non atopic is synonymous with non allergic is called into question by epidemiological data that the prevalence of asthma is closely related to the serum IgE level standardized for age and sex P lt 0 0001 indicating that asthma is almost always associated with some sort of IgE related reaction and therefore has an allergic basis although not all the allergic stimuli that cause asthma appear to have been included in the battery of aeroallergens studied the missing antigen s hypothesis 131 For example an updated systematic review and meta analysis of population attributable risk PAR of Chlamydia pneumoniae biomarkers in chronic asthma found that the PAR for C pneumoniae specific IgE was 47 132 Infectious asthma Infectious asthma is an easily identified clinical presentation 133 When queried asthma patients may report that their first asthma symptoms began after an acute lower respiratory tract illness This type of history has been labelled the infectious asthma IA syndrome 134 or as asthma associated with infection AAWI 135 to distinguish infection associated asthma initiation from the well known association of respiratory infections with asthma exacerbations Reported clinical prevalences of IA for adults range from around 40 in a primary care practice 134 to 70 in a specialty practice treating mainly severe asthma patients 136 Additional information on the clinical prevalence of IA in adult onset asthma is unavailable because clinicians are not trained to elicit this type of history routinely and recollection in child onset asthma is challenging A population based incident case control study in a geographically defined area of Finland reported that 35 8 of new onset asthma cases had experienced acute bronchitis or pneumonia in the year preceding asthma onset representing a significantly higher risk compared to randomly selected controls Odds ratio 7 2 95 confidence interval 5 2 10 137 Phenotyping and endotyping Main article Asthma phenotyping and endotyping Asthma phenotyping and endotyping has emerged as a novel approach to asthma classification inspired by precision medicine which separates the clinical presentations of asthma or asthma phenotypes from their underlying causes or asthma endotypes The best supported endotypic distinction is the type 2 high type 2 low distinction Classification based on type 2 inflammation is useful in predicting which patients will benefit from targeted biologic therapy 138 139 Differential diagnosis Many other conditions can cause symptoms similar to those of asthma In children symptoms may be due to other upper airway diseases such as allergic rhinitis and sinusitis as well as other causes of airway obstruction including foreign body aspiration tracheal stenosis laryngotracheomalacia vascular rings enlarged lymph nodes or neck masses 140 Bronchiolitis and other viral infections may also produce wheezing 141 According to European Respiratory Society it may not be suitable to label wheezing preschool children with the term asthma because there is lack of clinical data on inflammation in airways 142 In adults COPD congestive heart failure airway masses as well as drug induced coughing due to ACE inhibitors may cause similar symptoms In both populations vocal cord dysfunction may present similarly 140 Chronic obstructive pulmonary disease can coexist with asthma and can occur as a complication of chronic asthma After the age of 65 most people with obstructive airway disease will have asthma and COPD In this setting COPD can be differentiated by increased airway neutrophils abnormally increased wall thickness and increased smooth muscle in the bronchi However this level of investigation is not performed due to COPD and asthma sharing similar principles of management corticosteroids long acting beta agonists and smoking cessation 143 It closely resembles asthma in symptoms is correlated with more exposure to cigarette smoke an older age less symptom reversibility after bronchodilator administration and decreased likelihood of family history of atopy 144 145 PreventionThe evidence for the effectiveness of measures to prevent the development of asthma is weak 146 The World Health Organization recommends decreasing risk factors such as tobacco smoke air pollution chemical irritants including perfume and the number of lower respiratory infections 147 148 Other efforts that show promise include limiting smoke exposure in utero breastfeeding and increased exposure to daycare or large families but none are well supported enough to be recommended for this indication 146 Early pet exposure may be useful 149 Results from exposure to pets at other times are inconclusive 150 and it is only recommended that pets be removed from the home if a person has allergic symptoms to said pet 151 Dietary restrictions during pregnancy or when breastfeeding have not been found to be effective at preventing asthma in children and are not recommended 151 Omega 3 consumption mediterranean diet and anti oxidants have been suggested by some studies that might help preventing crisis but the evidence is still inconclusive 152 Reducing or eliminating compounds known to sensitive people from the work place may be effective 123 It is not clear if annual influenza vaccinations affects the risk of exacerbations 153 Immunization however is recommended by the World Health Organization 154 Smoking bans are effective in decreasing exacerbations of asthma 155 ManagementWhile there is no cure for asthma symptoms can typically be improved 156 The most effective treatment for asthma is identifying triggers such as cigarette smoke pets or other allergens and eliminating exposure to them If trigger avoidance is insufficient the use of medication is recommended Pharmaceutical drugs are selected based on among other things the severity of illness and the frequency of symptoms Specific medications for asthma are broadly classified into fast acting and long acting categories 157 158 The medications listed below have demonstrated efficacy in improving asthma symptoms however real world use effectiveness is limited as around half of people with asthma worldwide remain sub optimally controlled even when treated 159 160 161 People with asthma may remain sub optimally controlled either because optimum doses of asthma medications do not work called refractory asthma or because individuals are either unable e g inability to afford treatment poor inhaler technique or unwilling e g wish to avoid side effects of corticosteroids to take optimum doses of prescribed asthma medications called difficult to treat asthma In practice it is not possible to distinguish refractory from difficult to treat categories for patients who have never taken optimum doses of asthma medications A related issue is that the asthma efficacy trials upon which the pharmacological treatment guidelines are based have systematically excluded the majority of people with asthma 162 163 For example asthma efficacy treatment trials always exclude otherwise eligible people who smoke and smoking diminishes the efficacy of inhaled corticosteroids the mainstay of asthma control management 164 165 166 Bronchodilators are recommended for short term relief of symptoms In those with occasional attacks no other medication is needed If mild persistent disease is present more than two attacks a week low dose inhaled corticosteroids or alternatively a leukotriene antagonist or a mast cell stabilizer by mouth is recommended For those who have daily attacks a higher dose of inhaled corticosteroids is used In a moderate or severe exacerbation corticosteroids by mouth are added to these treatments 8 People with asthma have higher rates of anxiety psychological stress and depression 167 168 This is associated with poorer asthma control 167 Cognitive behavioral therapy may improve quality of life asthma control and anxiety levels in people with asthma 167 Improving people s knowledge about asthma and using a written action plan has been identified as an important component of managing asthma 169 Providing educational sessions that include information specific to a person s culture is likely effective 170 More research is necessary to determine if increasing preparedness and knowledge of asthma among school staff and families using home based and school interventions results in long term improvements in safety for children with asthma 171 172 173 School based asthma self management interventions which attempt to improve knowledge of asthma its triggers and the importance of regular practitioner review may reduce hospital admissions and emergency department visits These interventions may also reduce the number of days children experience asthma symptoms and may lead to small improvements in asthma related quality of life 174 More research is necessary to determine if shared decision making is helpful for managing adults with asthma 175 or if a personalized asthma action plan is effective and necessary 176 Some people with asthma use pulse oximeters to monitor their own blood oxygen levels during an asthma attack However there is no evidence regarding the use in these instances 177 Lifestyle modification Avoidance of triggers is a key component of improving control and preventing attacks The most common triggers include allergens smoke from tobacco or other sources air pollution nonselective beta blockers and sulfite containing foods 178 179 Cigarette smoking and second hand smoke passive smoke may reduce the effectiveness of medications such as corticosteroids 180 Laws that limit smoking decrease the number of people hospitalized for asthma 155 Dust mite control measures including air filtration chemicals to kill mites vacuuming mattress covers and others methods had no effect on asthma symptoms 64 There is insufficient evidence to suggest that dehumidifiers are helpful for controlling asthma 181 Overall exercise is beneficial in people with stable asthma 182 Yoga could provide small improvements in quality of life and symptoms in people with asthma 183 More research is necessary to determine how effective weight loss is on improving quality of life the usage of health care services and adverse effects for people of all ages with asthma 184 185 Medications Medications used to treat asthma are divided into two general classes quick relief medications used to treat acute symptoms and long term control medications used to prevent further exacerbation 157 Antibiotics are generally not needed for sudden worsening of symptoms or for treating asthma at any time 186 187 Medications for asthma exacerbations nbsp Salbutamol metered dose inhaler commonly used to treat asthma attacksShort acting beta2 adrenoceptor agonists SABA such as salbutamol albuterol USAN are the first line treatment for asthma symptoms 8 They are recommended before exercise in those with exercise induced symptoms 188 Anticholinergic medications such as ipratropium provide additional benefit when used in combination with SABA in those with moderate or severe symptoms and may prevent hospitalizations 8 189 190 Anticholinergic bronchodilators can also be used if a person cannot tolerate a SABA 105 If a child requires admission to hospital additional ipratropium does not appear to help over a SABA 191 For children over 2 years old with acute asthma symptoms inhaled anticholinergic medications taken alone is safe but is not as effective as inhaled SABA or SABA combined with inhaled anticholinergic medication 192 189 Adults who receive combined inhaled medications that includes short acting anticholinergics and SABA may be at risk for increased adverse effects such as experiencing a tremor agitation and heart beat palpitations compared to people who are treated with SABA by itself 190 Older less selective adrenergic agonists such as inhaled epinephrine have similar efficacy to SABAs 193 They are however not recommended due to concerns regarding excessive cardiac stimulation 194 Corticosteroids can also help with the acute phase of an exacerbation because of their antiinflamatory properties The benefit of systemic and oral corticosteroids is well established Inhaled or nebulized corticosteroids can also be used 152 For adults and children who are in the hospital due to acute asthma systemic IV corticosteroids improve symptoms 195 196 A short course of corticosteroids after an acute asthma exacerbation may help prevent relapses and reduce hospitalizations 197 Other remedies less established are intravenous or nebulized magnesium sulfate and helium mixed with oxygen Aminophylline could be used with caution as well 152 Mechanical ventilation is the last resort in case of severe hypoxemia 152 Intravenous administration of the drug aminophylline does not provide an improvement in bronchodilation when compared to standard inhaled beta 2 agonist treatment 198 Aminophylline treatment is associated with more adverse effects compared to inhaled beta 2 agonist treatment 198 Long term control nbsp Fluticasone propionate metered dose inhaler commonly used for long term controlCorticosteroids are generally considered the most effective treatment available for long term control 157 Inhaled forms are usually used except in the case of severe persistent disease in which oral corticosteroids may be needed 157 Dosage depends on the severity of symptoms 199 High dosage and long term use might lead to the appearance of common adverse effects which are growth delay adrenal suppression and osteoporosis 152 Continuous daily use of an inhaled corticosteroid rather than its intermitted use seems to provide better results in controlling asthma exacerbations 152 Commonly used corticosteroids are budesonide fluticasone mometasone and ciclesonide 152 Long acting beta adrenoceptor agonists LABA such as salmeterol and formoterol can improve asthma control at least in adults when given in combination with inhaled corticosteroids 200 201 In children this benefit is uncertain 200 202 201 When used without steroids they increase the risk of severe side effects 203 and with corticosteroids they may slightly increase the risk 204 205 Evidence suggests that for children who have persistent asthma a treatment regime that includes LABA added to inhaled corticosteroids may improve lung function but does not reduce the amount of serious exacerbations 206 Children who require LABA as part of their asthma treatment may need to go to the hospital more frequently 206 Leukotriene receptor antagonists anti leukotriene agents such as montelukast and zafirlukast may be used in addition to inhaled corticosteroids typically also in conjunction with a LABA 17 207 208 209 For adults or adolescents who have persistent asthma that is not controlled very well the addition of anti leukotriene agents along with daily inhaled corticosteriods improves lung function and reduces the risk of moderate and severe asthma exacerbations 208 Anti leukotriene agents may be effective alone for adolescents and adults however there is no clear research suggesting which people with asthma would benefit from anti leukotriene receptor alone 210 In those under five years of age anti leukotriene agents were the preferred add on therapy after inhaled corticosteroids 152 211 A 2013 Cochrane systematic review concluded that anti leukotriene agents appear to be of little benefit when added to inhaled steroids for treating children 212 A similar class of drugs 5 LOX inhibitors may be used as an alternative in the chronic treatment of mild to moderate asthma among older children and adults 17 213 As of 2013 update there is one medication in this family known as zileuton 17 Mast cell stabilizers such as cromolyn sodium are safe alternatives to corticosteroids but not preferred because they have to be administered frequently 157 17 Oral Theophyllines are sometimes used for controlling chronic asthma but their used is minimized because of their side effects 152 Omalizumab a monoclonal Antibody Against IgE is a novel way to lessen exacerbations by decreasing the levels of circulating IgE that play a significant role at allergic asthma 152 214 Anticholinergic medications such as ipratropium bromide have not been shown to be beneficial for treating chronic asthma in children over 2 years old 215 but is not suggested for routine treatment of chronic asthma in adults 216 There is no strong evidence to recommend chloroquine medication as a replacement for taking corticosteroids by mouth for those who are not able to tolerate inhaled steroids 217 Methotrexate is not suggested as a replacement for taking corticosteriods by mouth steroid sparing due to the adverse effects associated with taking methotrexate and the minimal relief provided for asthma symptoms 218 Macrolide antibiotics particularly the azalide macrolide azithromycin are a recently added GINA recommended treatment option for both eosinophilic and non eosinophilic severe refractory asthma based on azithromycin s efficacy in reducing moderate and severe exacerbations combined 219 220 Azithromycin s mechanism of action is not established and could involve pathogen and or host directed anti inflammatory activities 221 Limited clinical observations suggest that some patients with new onset asthma and with difficult to treat asthma including those with the asthma COPD overlap syndrome ACOS may respond dramatically to azithromycin 222 223 However these groups of asthma patients have not been studied in randomized treatment trials and patient selection needs to be carefully individualized For children with asthma which is well controlled on combination therapy of inhaled corticosteroids ICS and long acting beta2 agonists LABA the benefits and harms of stopping LABA and stepping down to ICS only therapy are uncertain 224 In adults who have stable asthma while they are taking a combination of LABA and inhaled corticosteroids ICS stopping LABA may increase the risk of asthma exacerbations that require treatment with corticosteroids by mouth 225 Stopping LABA probably makes little or no important difference to asthma control or asthma related quality of life 225 Whether or not stopping LABA increases the risk of serious adverse events or exacerbations requiring an emergency department visit or hospitalisation is uncertain 225 Delivery methods Medications are typically provided as metered dose inhalers MDIs in combination with an asthma spacer or as a dry powder inhaler The spacer is a plastic cylinder that mixes the medication with air making it easier to receive a full dose of the drug A nebulizer may also be used Nebulizers and spacers are equally effective in those with mild to moderate symptoms However insufficient evidence is available to determine whether a difference exists in those with severe disease 226 For delivering short acting beta agonists in acute asthma in children spacers may have advantages compared to nebulisers but children with life threatening asthma have not been studied 227 There is no strong evidence for the use of intravenous LABA for adults or children who have acute asthma 228 There is insufficient evidence to directly compare the effectiveness of a metered dose inhaler attached to a homemade spacer compared to commercially available spacer for treating children with asthma 229 Adverse effects Long term use of inhaled corticosteroids at conventional doses carries a minor risk of adverse effects 230 Risks include thrush the development of cataracts and a slightly slowed rate of growth 230 231 232 Rinsing the mouth after the use of inhaled steroids can decrease the risk of thrush 233 Higher doses of inhaled steroids may result in lower bone mineral density 234 Others Inflammation in the lungs can be estimated by the level of exhaled nitric oxide 235 236 The use of exhaled nitric oxide levels FeNO to guide asthma medication dosing may have small benefits for preventing asthma attacks but the potential benefits are not strong enough for this approach to be universally recommended as a method to guide asthma therapy in adults or children 235 236 When asthma is unresponsive to usual medications other options are available for both emergency management and prevention of flareups Additional options include Humidified oxygen to alleviate hypoxia if saturations fall below 92 152 Corticosteroid by mouth are recommended with five days of prednisone being the same 2 days of dexamethasone 237 One review recommended a seven day course of steroids 238 Magnesium sulfate intravenous treatment increases bronchodilation when used in addition to other treatment in moderate severe acute asthma attacks 18 239 240 In adults intravenous treatment results in a reduction of hospital admissions 241 Low levels of evidence suggest that inhaled nebulised magnesium sulfate may have a small benefit for treating acute asthma in adults 242 Overall high quality evidence do not indicate a large benefit for combining magnesium sulfate with standard inhaled treatments for adults with asthma 242 Heliox a mixture of helium and oxygen may also be considered in severe unresponsive cases 18 Intravenous salbutamol is not supported by available evidence and is thus used only in extreme cases 243 Methylxanthines such as theophylline were once widely used but do not add significantly to the effects of inhaled beta agonists 243 Their use in acute exacerbations is controversial 244 The dissociative anesthetic ketamine is theoretically useful if intubation and mechanical ventilation is needed in people who are approaching respiratory arrest however there is no evidence from clinical trials to support this 245 A 2012 Cochrane review found no significant benefit from the use of ketamine in severe acute asthma in children 246 For those with severe persistent asthma not controlled by inhaled corticosteroids and LABAs bronchial thermoplasty may be an option 247 It involves the delivery of controlled thermal energy to the airway wall during a series of bronchoscopies 247 248 While it may increase exacerbation frequency in the first few months it appears to decrease the subsequent rate Effects beyond one year are unknown 249 Monoclonal antibody injections such as mepolizumab 250 dupilumab 251 or omalizumab may be useful in those with poorly controlled atopic asthma 252 However as of 2019 update these medications are expensive and their use is therefore reserved for those with severe symptoms to achieve cost effectiveness 253 Monoclonal antibodies targeting interleukin 5 IL 5 or its receptor IL 5R including mepolizumab reslizumab or benralizumab in addition to standard care in severe asthma is effective in reducing the rate of asthma exacerbations There is limited evidence for improved health related quality of life and lung function 254 Evidence suggests that sublingual immunotherapy in those with both allergic rhinitis and asthma improve outcomes 255 It is unclear if non invasive positive pressure ventilation in children is of use as it has not been sufficiently studied 256 Adherence to asthma treatments Staying with a treatment approach for preventing asthma exacerbations can be challenging especially if the person is required to take medicine or treatments daily 257 Reasons for low adherence range from a conscious decision to not follow the suggested medical treatment regime for various reasons including avoiding potential side effects misinformation or other beliefs about the medication 257 Problems accessing the treatment and problems administering the treatment effectively can also result in lower adherence Various approaches have been undertaken to try and improve adherence to treatments to help people prevent serious asthma exacerbations including digital interventions 257 Alternative medicine Many people with asthma like those with other chronic disorders use alternative treatments surveys show that roughly 50 use some form of unconventional therapy 258 259 There is little data to support the effectiveness of most of these therapies Evidence is insufficient to support the usage of vitamin C or vitamin E for controlling asthma 260 261 There is tentative support for use of vitamin C in exercise induced bronchospasm 262 Fish oil dietary supplements marine n 3 fatty acids 263 and reducing dietary sodium 264 do not appear to help improve asthma control In people with mild to moderate asthma treatment with vitamin D supplementation or its hydroxylated metabolites does not reduce acute exacerbations or improve control 265 There is no strong evidence to suggest that vitamin D supplements improve day to day asthma symptoms or a person s lung function 265 There is no strong evidence to suggest that adults with asthma should avoid foods that contain monosodium glutamate MSG 266 There have not been enough high quality studies performed to determine if children with asthma should avoid eating food that contains MSG 266 Acupuncture is not recommended for the treatment as there is insufficient evidence to support its use 267 268 Air ionisers show no evidence that they improve asthma symptoms or benefit lung function this applied equally to positive and negative ion generators 269 Manual therapies including osteopathic chiropractic physiotherapeutic and respiratory therapeutic maneuvers have insufficient evidence to support their use in treating asthma 270 Pulmonary rehabilitation however may improve quality of life and functional exercise capacity when compared to usual care for adults with asthma 271 The Buteyko breathing technique for controlling hyperventilation may result in a reduction in medication use however the technique does not have any effect on lung function 158 Thus an expert panel felt that evidence was insufficient to support its use 267 There is no clear evidence that breathing exercises are effective for treating children with asthma 272 PrognosisThe prognosis for asthma is generally good especially for children with mild disease 273 Mortality has decreased over the last few decades due to better recognition and improvement in care 274 In 2010 the death rate was 170 per million for males and 90 per million for females 275 Rates vary between countries by 100 fold 275 Globally it causes moderate or severe disability in 19 4 million people as of 2004 update 16 million of which are in low and middle income countries 276 Of asthma diagnosed during childhood half of cases will no longer carry the diagnosis after a decade 77 Airway remodeling is observed but it is unknown whether these represent harmful or beneficial changes 277 More recent data find that severe asthma can result in airway remodeling and the asthma with chronic obstructive pulmonary disease syndrome ACOS that has a poor prognosis 278 Early treatment with corticosteroids seems to prevent or ameliorates a decline in lung function 279 Asthma in children also has negative effects on quality of life of their parents 280 nbsp Asthma deaths per million persons in 2012 0 10 11 13 14 17 18 23 24 32 33 43 44 50 51 66 67 95 96 251 nbsp Disability adjusted life year for asthma per 100 000 inhabitants in 2004 281 no data 0 100 100 150 150 200 200 250 250 300 300 350 350 400 400 450 450 500 500 550 550 600 gt 600EpidemiologyMain article Epidemiology of asthma nbsp Rates of asthma in 2017 282 In 2019 approximately 262 million people worldwide were affected by asthma and approximately 461 000 people died from the disease 9 Rates vary between countries with prevalences between 1 and 18 22 It is more common in developed than developing countries 22 One thus sees lower rates in Asia Eastern Europe and Africa 21 Within developed countries it is more common in those who are economically disadvantaged while in contrast in developing countries it is more common in the affluent 22 The reason for these differences is not well known 22 Low and middle income countries make up more than 80 of the mortality 283 While asthma is twice as common in boys as girls 22 severe asthma occurs at equal rates 284 In contrast adult women have a higher rate of asthma than men 22 and it is more common in the young than the old 21 In 2010 children with asthma experienced over 900 000 emergency department visits making it the most common reason for admission to the hospital following an emergency department visit in the US in 2011 285 286 Global rates of asthma have increased significantly between the 1960s and 2008 19 287 with it being recognized as a major public health problem since the 1970s 21 Rates of asthma have plateaued in the developed world since the mid 1990s with recent increases primarily in the developing world 288 Asthma affects approximately 7 of the population of the United States 203 and 5 of people in the United Kingdom 289 Canada Australia and New Zealand have rates of about 14 15 290 The average death rate from 2011 to 2015 from asthma in the UK was about 50 higher than the average for the European Union and had increased by about 5 in that time 291 Children are more likely see a physician due to asthma symptoms after school starts in September 292 Population based epidemiological studies describe temporal associations between acute respiratory illnesses asthma and development of severe asthma with irreversible airflow limitation known as the asthma chronic obstructive pulmonary disease overlap syndrome or ACOS 293 294 295 Additional prospective population based data indicate that ACOS seems to represent a form of severe asthma characterised by more frequent hospitalisations and to be the result of early onset asthma that has progressed to fixed airflow obstruction 296 EconomicsFrom 2000 to 2010 the average cost per asthma related hospital stay in the United States for children remained relatively stable at about 3 600 whereas the average cost per asthma related hospital stay for adults increased from 5 200 to 6 600 297 In 2010 Medicaid was the most frequent primary payer among children and adults aged 18 44 years in the United States private insurance was the second most frequent payer 297 Among both children and adults in the lowest income communities in the United States there is a higher rate of hospital stays for asthma in 2010 than those in the highest income communities 297 History nbsp Ebers Papyrus detailing treatment of asthma nbsp 1907 advertisement for Grimault s Indian Cigarettes promoted as a means of relieving asthma They contained belladonna and cannabis nbsp The Gold dust Book of Cold Damage dated 1st year of the Zhengyuan reign period of the Yuan dynasty 1341 Wellcome Asthma was recognized in ancient Egypt and was treated by drinking an incense mixture known as kyphi 20 It was officially named as a specific respiratory problem by Hippocrates circa 450 BC with the Greek word for panting forming the basis of our modern name 21 In 200 BC it was believed to be at least partly related to the emotions 29 In the 12th century the Jewish physician philosopher Maimonides wrote a treatise on asthma in Arabic based partly on Arabic sources in which he discussed the symptoms proposed various dietary and other means of treatment and emphasized the importance of climate and clean air 298 Chinese Traditional Medicine also offered medication for asthma as indicated by a surviving 14th century manuscript curated by the Wellcome Foundation 299 In 1873 one of the first papers in modern medicine on the subject tried to explain the pathophysiology of the disease while one in 1872 concluded that asthma can be cured by rubbing the chest with chloroform liniment 300 301 Medical treatment in 1880 included the use of intravenous doses of a drug called pilocarpine 302 In 1886 F H Bosworth theorized a connection between asthma and hay fever 303 Epinephrine was first referred to in the treatment of asthma in 1905 304 Oral corticosteroids began to be used for this condition in the 1950s while inhaled corticosteroids and selective short acting beta agonist came into wide use in the 1960s 305 306 A well documented case in the 19th century was that of young Theodore Roosevelt 1858 1919 At that time there was no effective treatment Roosevelt s youth was in large part shaped by his poor health partly related to his asthma He experienced recurring nighttime asthma attacks that felt as if he was being smothered to death terrifying the boy and his parents 307 During the 1930s to 1950s asthma was known as one of the holy seven psychosomatic illnesses Its cause was considered to be psychological with treatment often based on psychoanalysis and other talking cures 308 As these psychoanalysts interpreted the asthmatic wheeze as the suppressed cry of the child for its mother they considered the treatment of depression to be especially important for individuals with asthma 308 In January 2021 an appeal court in France overturned a deportation order against a 40 year old Bangladeshi man who was a patient of asthma His lawyers had argued that the dangerous levels of pollution in Bangladesh could possibly lead to worsening of his health condition or even premature death 309 Notes GINA 2011 p 18 Jones D 2011 Roach P Setter J Esling J eds Cambridge English Pronouncing Dictionary 18th ed Cambridge University Press ISBN 978 0 521 15255 6 Wells JC 2008 Longman Pronunciation Dictionary 3rd ed Longman ISBN 978 1 4058 8118 0 a b c d Drazen GM Bel EH 2020 81 Asthma In Goldman L Schafer AI eds Goldman Cecil Medicine Vol 1 26th ed Philadelphia Elsevier pp 527 535 ISBN 978 0 323 55087 1 a b c d e f g h i j Asthma Fact sheet 307 WHO 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