Asthma

Asthma is a common long-term inflammatory disease of the airways of the lungs.<ref name="WHO2013" /> It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms.<ref name="NHLBI07p11-12">Template:Harvnb</ref><ref name="GINA_2011_page20,51">Template:Harvnb</ref> Symptoms include episodes of wheezing, coughing, chest tightness, and shortness of breath.<ref name="Goldman2020" /> A sudden worsening of asthma symptoms sometimes called an 'asthma attack' or an 'asthma exacerbation' can occur when allergens, pollen, dust, or other particles, are inhaled into the lungs, causing the bronchioles to constrict and produce mucus, which then restricts oxygen flow to the alveoli. These may occur a few times a day or a few times per week.<ref name="WHO2013" /> Depending on the person, asthma symptoms may become worse at night or with exercise.<ref name="WHO2013" />

Asthma is thought to be caused by a combination of genetic and environmental factors.<ref name=Goldman2020>Template:Cite book</ref> Environmental factors include exposure to air pollution and allergens.<ref name=WHO2013/> Other potential triggers include medications such as aspirin and beta blockers.<ref name=WHO2013/> Diagnosis is usually based on the pattern of symptoms, response to therapy over time, and spirometry lung function testing.<ref name="Lemanske2010">Template:Cite journal</ref> Asthma is classified according to the frequency of symptoms of forced expiratory volume in one second (FEV₁), and peak expiratory flow rate.<ref name=Yawn2008>Template:Cite journal</ref> It may also be classified as atopic or non-atopic, where atopy refers to a predisposition toward developing a type 1 hypersensitivity reaction.<ref name=RobbinsCotran2010>Template:Cite book</ref><ref>Template:Cite book</ref>

There is no known cure for asthma, but it can be controlled.<ref name=WHO2013/> Symptoms can be prevented by avoiding triggers, such as allergens and respiratory irritants, and suppressed with the use of inhaled corticosteroids.<ref name="NHLBI07p169">Template:Harvnb</ref><ref name=GINA_2011_page71>Template:Harvnb</ref> Long-acting beta agonists (LABA) or antileukotriene agents may be used in addition to inhaled corticosteroids if asthma symptoms remain uncontrolled.<ref name=GINA_2011_page33>Template:Harvnb</ref><ref name="Antileukotriene agents">Template:Cite journal</ref> Treatment of rapidly worsening symptoms is usually with an inhaled short-acting beta₂ agonist such as salbutamol and corticosteroids taken by mouth.<ref name=NHLBI07p214>Template:Harvnb</ref> In very severe cases, intravenous corticosteroids, magnesium sulfate, and hospitalization may be required.<ref name=NHLBI07p373>Template:Harvnb</ref>

In 2019, asthma affected approximately 262Template:Nbspmillion people and caused approximately 461,000 deaths.<ref name="lancetasthma" /> Most of the deaths occurred in the developing world.<ref name=WHO2013/> Asthma often begins in childhood,<ref name="WHO2013">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and the rates have increased significantly since the 1960s.<ref name=Ana2010>Template:Cite journal</ref> Asthma was recognized as early as Ancient Egypt.<ref name="Manniche1999">Template:Cite book</ref> The word asthma is from the Greek {{#invoke:Lang|lang}} (Template:Transliteration), which means 'panting'.<ref name=M38>Template:Cite book</ref> Template:TOC limit

Signs and symptoms

{{#invoke:Listen|main}} Asthma is characterized by recurrent episodes symptomes of wheezing, shortness of breath, chest tightness, and coughing.<ref name="GINA2011p2">Template:Harvnb</ref> Sputum may be produced from the lung by coughing but is often hard to bring up.<ref>Template:Cite book</ref> During recovery from an asthma attack (exacerbation), the sputum may appear pus-like due to high levels of white blood cells called eosinophils.<ref>Template:Cite book</ref> Symptoms are usually worse at night and in the early morning or in response to exercise or cold air.<ref name=bts2009p14>Template:Harvnb</ref> Some people with asthma rarely experience symptoms, usually in response to triggers, whereas others may react frequently and readily and experience persistent symptoms.<ref name="GINA2011_p8-9">Template:Harvnb</ref>

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.<ref name=Boulet2009>Template:Cite journal</ref> Psychological disorders are also more common,<ref name="Boulay2011">Template:Cite journal</ref> with anxiety disorders occurring in between 16 and 52% and mood disorders in 14–41%.<ref name="Andrew2010">Template:Cite book</ref> It is not known whether asthma causes psychological problems or psychological problems lead to asthma.<ref>Template:Cite journal</ref> Current asthma, but not former asthma, is associated with increased all-cause mortality, heart disease mortality, and chronic lower respiratory tract disease mortality.<ref>Template:Cite journal</ref> Asthma, particularly severe asthma, is strongly associated with development of chronic obstructive pulmonary disease (COPD).<ref name="Asthma as a risk factor for COPD in">Template:Cite journal</ref><ref name="Asthma, COPD and overlap syndrome">Template:Cite journal</ref><ref>Template:Cite journal</ref> Those with asthma, especially if it is poorly controlled, are at increased risk for radiocontrast reactions.<ref>Template:Cite book</ref>

Cavities occur more often in people with asthma.<ref>Template:Cite journal</ref> This may be related to the effect of beta₂-adrenergic agonists decreasing saliva.<ref name=Tho2010>Template:Cite journal</ref> These medications may also decrease the risk of dental erosions.<ref name="Tho2010" />

Causes

Asthma is caused by a combination of complex and incompletely understood environmental and genetic interactions.<ref name=Martinez2007>Template:Cite journal</ref><ref>Template:Cite journal</ref> These influence both its severity and its responsiveness to treatment.<ref>Template:Cite journal</ref> 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.<ref name="pmid21575714">Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

Environmental

Many environmental factors have been associated with asthma's development and exacerbation, including allergens, air pollution, and other environmental chemicals.<ref name="pmid21623970">Template:Cite journal</ref> 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, moulds.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Smoking during pregnancy and after delivery is associated with a greater risk of asthma-like symptoms.<ref name="GINA2011_p6">Template:Harvnb</ref> Low air quality from environmental factors such as traffic pollution or high ozone levels<ref name="GINA2011_p61">Template:Harvnb</ref> has been associated with both asthma development and increased asthma severity.<ref name="Gold">Template:Cite journal</ref> Over half of cases in children in the United States occur in areas when air quality is below the EPA standards.<ref>Template:Cite journal</ref> Low air quality is more common in low-income and minority communities.<ref>Template:Cite journal</ref>

Exposure to indoor volatile organic compounds may be a trigger for asthma; formaldehyde exposure, for example, has a positive association.<ref name="pmid20064771">Template:Cite journal</ref> Phthalates in certain types of PVC are associated with asthma in both children and adults.<ref>Template:Cite journal</ref><ref name="pmid20059582">Template:Cite journal</ref> While exposure to pesticides is linked to the development of asthma, a cause and effect relationship has yet to be established.<ref name="MamJune2015">Template:Cite journal</ref><ref name="MamSept2015">Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

Pregnancy

The evidence does not support a causal role between paracetamol (acetaminophen) or antibiotic use and asthma.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> A 2014 systematic review found that the association between paracetamol use and asthma disappeared when respiratory infections were taken into account.<ref>Template:Cite journal</ref> Maternal psychological stress during pregnancy is a risk factor for the child to develop asthma.<ref>Template:Cite journal</ref>

Allergens

Asthma is associated with exposure to indoor allergens.<ref name="pmid21301330">Template:Cite journal</ref> Common indoor allergens include dust mites, cockroaches, animal dander (fragments of fur or feathers), and mould.<ref name=Arshad>Template:Cite journal</ref><ref>Template:Cite journal</ref> Efforts to decrease dust mites have been found to be ineffective on symptoms in sensitized subjects.<ref name=Gotzsche2008/><ref>Template:Cite journal</ref> Weak evidence suggests that efforts to decrease mould by repairing buildings may help improve asthma symptoms in adults.<ref>Template:Cite journal</ref> Certain viral respiratory infections, such as respiratory syncytial virus and rhinovirus,<ref name=M38/> may increase the risk of developing asthma when acquired as young children.<ref name=NHLBI07p11>Template:Harvnb</ref> Certain other infections, however, may decrease the risk.<ref name=M38/>

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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> 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.<ref name=Brook2013>Template:Cite journal</ref> Exposure to bacterial endotoxin in early childhood may prevent the development of asthma, but exposure at an older age may provoke bronchoconstriction.<ref>Template:Cite journal</ref> Evidence supporting the hygiene hypothesis includes lower rates of asthma on farms and in households with pets.<ref name=Brook2013/>

Use of antibiotics in early life has been linked to the development of asthma.<ref>Template:Cite journal</ref> 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.<ref>Template:Harvnb</ref><ref name="pmid21645799">Template:Cite journal</ref> 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.<ref name="pmid14763924">Template:Cite journal</ref>

Genetic

CD14-endotoxin interaction based on CD14 SNP C-159T<ref name=Martinez_CD14 />

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.<ref name=El2010>Template:Cite book</ref> If one identical twin is affected, the probability of the other having the disease is approximately 25%.<ref name=El2010/> 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.<ref name=Hoffjan/> 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.<ref name=Hoffjan /> In 2006 over 100 genes were associated with asthma in one genetic association study alone;<ref name=Hoffjan>Template:Cite journal</ref> more continue to be found.<ref name="pmid20298365">Template:Cite journal</ref>

Some genetic variants may only cause asthma when they are combined with specific environmental exposures.<ref name=Martinez2007/> 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.<ref name=Martinez_CD14>Template:Cite journal</ref>

Medical conditions

A triad of atopic eczema, allergic rhinitis and asthma is called atopy.<ref name="Bolognia" /> The strongest risk factor for developing asthma is a history of atopic disease;<ref name=NHLBI07p11/> with asthma occurring at a much greater rate in those who have either eczema or hay fever.<ref name="GINA2011_p4">Template:Harvnb</ref> Asthma has been associated with eosinophilic granulomatosis with polyangiitis (formerly known as Churg–Strauss syndrome), an autoimmune disease and vasculitis.<ref name="ChapelHill">Template:Cite journal</ref> Individuals with certain types of urticaria may also experience symptoms of asthma.<ref name="Bolognia">Template:Cite book</ref>

There is a correlation between obesity and the risk of asthma with both having increased in recent years.<ref>Template:Cite journal</ref><ref name=holguin>Template:Cite journal</ref> 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.<ref name="Woods 2009">Template:Cite journal</ref>

Beta blocker medications such as propranolol can trigger asthma in those who are susceptible.<ref name="pmid17998992">Template:Cite journal</ref> Cardioselective beta-blockers, however, appear safe in those with mild or moderate disease.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Other medications that can cause problems in asthmatics are angiotensin-converting enzyme inhibitors, aspirin, and NSAIDs.<ref name="pmid15579370">Template:Cite journal</ref> Use of acid-suppressing medication (proton pump inhibitors and H2 blockers) during pregnancy is associated with an increased risk of asthma in the child.<ref>Template:Cite journal</ref>

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.<ref name=Baxi2010>Template:Cite journal</ref> Most individuals can develop severe exacerbation from a number of triggering agents.<ref name=Baxi2010/>

Home factors that can lead to exacerbation of asthma include dust, animal dander (especially cat and dog hair), cockroach allergens and mold.<ref name=Baxi2010/><ref>Template:Cite journal</ref> 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.<ref name=Baxi2010/> 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.<ref name=Gold/><ref name="Chen2007">Template:Cite journal</ref>

Asthma exacerbations in school-aged children peak in autumn for 8 weeks, 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.<ref name="PikeAkhbari2018">Template:Cite journal</ref>

Pathophysiology

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Template:Multiple image 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.<ref name=GINA2011p2/> 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.<ref name=GINA2011p2/> Typical changes in the airways include an increase in eosinophils and thickening of the lamina reticularis.<ref name=M38/> Chronically, the airways' smooth muscle may increase in size along with an increase in the numbers of mucous glands.<ref name=M38/> 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.<ref name=M38/>

Diagnosis

While asthma is a well-recognized condition, there is not one universal agreed-upon definition.<ref name=M38/> 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".<ref name=GINA2011p2 />

There is currently no precise test for the diagnosis, which is typically based on the pattern of symptoms and response to therapy over time.<ref name=Lemanske2010/><ref name=M38/> 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.<ref name=NAEPP42>Template:Harvnb</ref> Spirometry is then used to confirm the diagnosis.<ref name=NAEPP42/> In children under the age of six the diagnosis is more difficult as they are too young for spirometry.<ref name=GINA2011p20>Template:Harvnb</ref>

Spirometry

Spirometry is recommended to aid in diagnosis and management.<ref name="AAAAIfive">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="NIHasthmaguide">Template:Cite book</ref> 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 millilitres 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.<ref name=M38/> As caffeine is a bronchodilator in people with asthma, the use of caffeine before a lung function test may interfere with the results.<ref name="pmid20091514">Template:Cite journal</ref> Single-breath diffusing capacity can help differentiate asthma from COPD.<ref name=M38/> It is reasonable to perform spirometry every one or two years to follow how well a person's asthma is controlled.<ref name=NHLBI07p58>Template:Harvnb</ref>

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.<ref name=M38/>

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.<ref>Template:Cite journal</ref> 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.<ref name=NAEPP2007p59>Template:Harvnb</ref>

Classification

Clinical classification (≥ 12 years old)<ref name=Yawn2008/>

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.<ref name="Yawn2008" /> 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).<ref name="RobbinsCotran2010" /> While asthma is classified based on severity, at the moment there is no clear method for classifying different subgroups of asthma beyond this system.<ref name=Moore2010>Template:Cite journal</ref> Finding ways to identify subgroups that respond well to different types of treatments is a current critical goal of asthma research.<ref name=Moore2010/> 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.<ref>Template:Cite book</ref>

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.<ref name="Self, Timothy 2009">Template:Cite book</ref> 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 remodelling.<ref name=Delacourt2004>Template:Cite journal</ref> In contrast to emphysema, asthma affects the bronchi, not the alveoli.<ref name=Schiffman2009>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref>Template:Cite journal</ref>

Asthma exacerbation

Severity of an acute exacerbation<ref name="BTS58" />

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.<ref name=M38/> The wheezing is most often when breathing out.<ref>Template:Cite book</ref> While these are the primary symptoms of asthma,<ref name=Barnes2008>Template:Cite book</ref> some people present primarily with coughing, and in severe cases, air motion may be significantly impaired such that no wheezing is heard.<ref name="BTS58" /> In children, chest pain is often present.<ref name="Mac2011">Template:Cite book</ref>

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.<ref name=Maitre1995>Template:Cite journal</ref> A blue colour of the skin and nails may occur from lack of oxygen.<ref name=Werner2001>Template:Cite journal</ref>

In a mild exacerbation the peak expiratory flow rate (PEFR) is ≥200 L/min, or ≥50% of the predicted best.<ref name="Shiber2006">Template:Cite journal</ref> 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.<ref name="Shiber2006" />

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.<ref name=Shah2012/> Half of cases are due to infections with others caused by allergen, air pollution, or insufficient or inappropriate medication use.<ref name="Shah2012">Template:Cite journal</ref>

Brittle asthma is a kind of asthma distinguishable by recurrent, severe attacks.<ref name=BTS58>Template:Harvnb</ref> 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.<ref name=BTS58/>

Exercise-induced

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Exercise can trigger bronchoconstriction both in people with or without asthma.<ref name=EIB2012>Template:Cite journal</ref> It occurs in most people with asthma and up to 20% of people without asthma.<ref name=EIB2012/> Exercise-induced bronchoconstriction is common in professional athletes. The highest rates are among cyclists (up to 45%), swimmers, and cross-country skiers.<ref name="Wuestenfeld">Template:Cite journal</ref> While it may occur with any weather conditions, it is more common when it is dry and cold.<ref name=GINA_2011_page17>Template:Harvnb</ref> Inhaled beta₂ agonists do not appear to improve athletic performance among those without asthma;<ref name="pmid18394123">Template:Cite journal</ref> however, oral doses may improve endurance and strength.<ref name="pmid17241101">Template:Cite journal</ref><ref name="pmid21142283">Template:Cite journal</ref>

Occupational

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Asthma as a result of (or worsened by) workplace exposures is a commonly reported occupational disease.<ref name=Baur2012/> Many cases, however, are not reported or recognized as such.<ref>Template:Cite book</ref><ref>Template:Cite book</ref> 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.<ref name=Baur2012>Template:Cite journal</ref>

Aspirin-exacerbated respiratory disease

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Aspirin-exacerbated respiratory disease (AERD), also known as aspirin-induced asthma, affects up to 9% of asthmatics.<ref>Template:Cite journal</ref> AERD consists of asthma, nasal polyps, sinus disease, and respiratory reactions to aspirin and other NSAID medications (such as ibuprofen and naproxen).<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> People often also develop loss of smell and most experience respiratory reactions to alcohol.<ref name=Ken2018>Template:Cite journal</ref>

Alcohol-induced asthma

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Alcohol may worsen asthmatic symptoms in up to a third of people.<ref name=Adams2013/> This may be even more common in some ethnic groups such as the Japanese and those with aspirin-exacerbated respiratory disease.<ref name=Adams2013/> Other studies have found improvement in asthmatic symptoms from alcohol.<ref name=Adams2013>Template:Cite journal</ref>

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.<ref name=Peter2014>Template:Cite journal</ref> 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).<ref>Template:Cite journal</ref> 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%.<ref>Template:Cite journal</ref>

Infectious asthma

Infectious asthma is an easily identified clinical presentation.<ref>Template:Cite journal</ref> 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,<ref name="Infectious asthma: a reemerging cli">Template:Cite journal</ref> or as "asthma associated with infection" (AAWI)<ref>Template:Cite journal</ref> 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<ref name="Infectious asthma: a reemerging cli" /> to 70% in a speciality practice treating mainly severe asthma patients.<ref name="Outcomes of Antibiotics in Adults w">Template:Cite journal</ref> 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).<ref>Template:Cite journal</ref>

Phenotyping and endotyping

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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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

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.<ref name=NAEPP46/> Bronchiolitis and other viral infections may also produce wheezing.<ref>Template:Cite book</ref> 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.<ref>Template:Cite journal</ref> 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.<ref name=NAEPP46>Template:Harvnb</ref>

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.<ref name=Gibson>Template:Cite journal</ref> 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.<ref name="pmid16880365">Template:Cite journal</ref><ref name="Applied Therapeutics 2009">Template:Cite book</ref>

Prevention

The evidence for the effectiveness of measures to prevent the development of asthma is weak.<ref name="NHLBI07p184" /> 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.<ref name=WHO2017Fact>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref> 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.<ref name="NHLBI07p184">Template:Harvnb</ref>

Early pet exposure may be useful.<ref name="pmid22235226">Template:Cite journal</ref> Results from exposure to pets at other times are inconclusive<ref name="pmid20053584">Template:Cite journal</ref> and it is only recommended that pets be removed from the home if a person has allergic symptoms to said pet.<ref name=Au2005/>

Dietary restrictions during pregnancy or when breastfeeding have not been found to be effective at preventing asthma in children and are not recommended.<ref name=Au2005>Template:Cite journal</ref> Omega-3 consumption, Mediterranean diet and antioxidants have been suggested by some studies to potentially help prevent crises but the evidence is still inconclusive.<ref name="BertrandSánchez2020">Template:Cite book</ref>

Reducing or eliminating compounds known to sensitive people from the workplace may be effective.<ref name=Baur2012/> It is not clear if annual influenza vaccinations affect the risk of exacerbations.<ref>Template:Cite journal</ref> Immunization, however, is recommended by the World Health Organization.<ref>Template:Cite journal</ref> Smoking bans are effective in decreasing exacerbations of asthma.<ref name="Effect of smoke-free legislation on">Template:Cite journal</ref>

Management

While there is no cure for asthma, symptoms can typically be improved.<ref>Template:Cite book</ref> The most effective treatment for asthma is identifying triggers, such as cigarette smoke, use of electronic cigarettes, pets or other allergens, and eliminating exposure to them.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref name="NHLBI07p213">Template:Harvnb</ref><ref name=BGMA08>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

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.<ref name="NHLBI07p214" />

People with asthma have higher rates of anxiety, psychological stress, and depression.<ref name=Kew2016/><ref>Template:Cite journal</ref> This is associated with poorer asthma control.<ref name=Kew2016/> Cognitive behavioural therapy may improve quality of life, asthma control, and anxiety levels in people with asthma.<ref name=Kew2016>Template:Cite journal</ref>

Improving people's knowledge about asthma and using a written action plan has been identified as an important component of managing asthma.<ref>Template:Cite journal</ref> Providing educational sessions that include information specific to a person's culture is likely effective.<ref name="McCallumMorris2017">Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>Template:Update inline<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref> More research is necessary to determine if shared decision-making is helpful for managing adults with asthma<ref>Template:Cite journal</ref> or if a personalized asthma action plan is effective and necessary.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

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.<ref name=NAEPP2007p69>Template:Harvnb</ref><ref name=thomson>Template:Cite journal</ref> Cigarette smoking and second-hand smoke (passive smoke) may reduce the effectiveness of medications such as corticosteroids.<ref name=Stap2011>Template:Cite journal</ref> Laws that limit smoking decrease the number of people hospitalized for asthma.<ref name="Effect of smoke-free legislation on" /> Dust mite control measures, including air filtration, chemicals to kill mites, vacuuming, mattress covers and other methods had no effect on asthma symptoms.<ref name=Gotzsche2008>Template:Cite journal</ref> There is insufficient evidence to suggest that dehumidifiers are helpful for controlling asthma.<ref>Template:Cite journal</ref>

Overall, exercise is beneficial in people with stable asthma.<ref>Template:Cite journal</ref> Yoga could provide small improvements in quality of life and symptoms in people with asthma.<ref>Template:Cite journal</ref> More research is necessary to determine how effective weight loss is in improving quality of life, the usage of health care services, and adverse effects for people of all ages with asthma.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Findings suggest that the Wim Hof Method may reduce inflammation in healthy and non-healthy participants as it increases epinephrine levels, causing an increase in interleukin-10 and a decrease in pro-inflammatory cytokines.<ref>Template:Cite journal</ref>

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.<ref name="NHLBI07p213" /> Antibiotics are generally not needed for sudden worsening of symptoms or for treating asthma at any time.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref>

Medications for asthma exacerbations

File:Salbutamol2.JPG

Salbutamol metered dose inhaler commonly used to treat asthma attacks

• Short-acting beta₂-adrenoceptor agonists (SABAs), such as salbutamol (albuterol USAN) are the first-line treatment for asthma symptoms.<ref name="NHLBI07p214" /> They are recommended before exercise in those with exercise-induced symptoms.<ref>Template:Cite journal</ref>
• 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.<ref name="NHLBI07p214" /><ref name="Griffiths_2013">Template:Cite journal</ref><ref name="Kirkland_2017">Template:Cite journal</ref> Anticholinergic bronchodilators can also be used if a person cannot tolerate a SABA.<ref name="Self, Timothy 2009" /> If a child requires admission to hospital additional ipratropium does not appear to help over a SABA.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref><ref name="Griffiths_2013" /> Adults who receive combined inhaled medications, which include 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 SABAs alone.<ref name="Kirkland_2017" />
• Older, less selective adrenergic agonists, such as inhaled epinephrine, have similar efficacy to SABAs.<ref name="Rodrigo">Template:Cite journal</ref> They are, however, not recommended due to concerns regarding excessive cardiac stimulation.<ref name="NHLBI07p351">Template:Harvnb</ref>
• Corticosteroids can also help with the acute phase of an exacerbation because of their antiinflammatory properties. The benefit of systemic and oral corticosteroids is well established. Inhaled or nebulized corticosteroids can also be used.<ref name="BertrandSánchez2020" /> For adults and children who are in the hospital due to acute asthma, systemic (IV) corticosteroids improve symptoms.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> A short course of corticosteroids after an acute asthma exacerbation may help prevent relapses and reduce hospitalizations.<ref>Template:Cite journal</ref>
• Other remedies, less established, are intravenous or nebulized magnesium sulfate and helium mixed with oxygen. Aminophylline could be used with caution as well.<ref name="BertrandSánchez2020" />
• Mechanical ventilation is the last resort in case of severe hypoxemia.<ref name="BertrandSánchez2020" />
• Intravenous administration of the drug aminophylline does not provide an improvement in bronchodilation when compared to standard inhaled beta₂ agonist treatment.<ref name=Nai2012>Template:Cite journal</ref> Aminophylline treatment is associated with more adverse effects compared to inhaled beta₂ agonist treatment.<ref name=Nai2012/>

Long–term control

File:Fluticasone.JPG

Fluticasone propionate metered dose inhaler commonly used for long-term control

• Corticosteroids are generally considered the most effective treatment available for long-term control.<ref name=NHLBI07p213/> Inhaled forms are usually used except in the case of severe persistent disease, in which oral corticosteroids may be needed.<ref name=NHLBI07p213/> Dosage depends on the severity of symptoms.<ref name="NHLBI07p218">Template:Harvnb</ref> High dosage and long-term use might lead to the appearance of common adverse effects which are growth delay, adrenal suppression, and osteoporosis.<ref name="BertrandSánchez2020" /> Continuous (daily) use of an inhaled corticosteroid, rather than its intermitted use, seems to provide better results in controlling asthma exacerbations.<ref name="BertrandSánchez2020" /> Commonly used corticosteroids are budesonide, fluticasone, mometasone and ciclesonide.<ref name="BertrandSánchez2020" />
• 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.<ref name=Ducharme2010>Template:Cite journal</ref><ref name=Duc2009>Template:Cite journal</ref> In children this benefit is uncertain.<ref name=Ducharme2010/><ref name="pmid20393943">Template:Cite journal</ref><ref name=Duc2009/> When used without steroids they increase the risk of severe side-effects,<ref name=Fanta2009>Template:Cite journal</ref> and with corticosteroids they may slightly increase the risk.<ref name=Cates2012>Template:Cite journal</ref><ref name="pmid18646149">Template:Cite journal</ref> 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.<ref name=Chau2015>Template:Cite journal</ref> Children who require LABA as part of their asthma treatment may need to go to the hospital more frequently.<ref name=Chau2015/>
• 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.<ref name="Antileukotriene agents" /><ref>Template:Cite journal</ref><ref name=Cha2017>Template:Cite journal</ref><ref name="pmid22592708">Template:Cite journal</ref> 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.<ref name=Cha2017/> 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.<ref>Template:Cite journal</ref> In those under five years of age, anti-leukotriene agents were the preferred add-on therapy after inhaled corticosteroids.<ref name="BertrandSánchez2020" /><ref name=bts2009p43>Template:Harvnb</ref> A 2013 Cochrane systematic review concluded that anti-leukotriene agents appear to be of little benefit when added to inhaled steroids for treating children.<ref>Template:Cite journal</ref> 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.<ref name="Antileukotriene agents" /><ref name="USFDA Zileuton">{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref> Template:As of there is one medication in this family known as zileuton.<ref name="Antileukotriene agents" />

• Mast cell stabilizers (such as cromolyn sodium) are safe alternatives to corticosteroids but not preferred because they have to be administered frequently.<ref name=NHLBI07p213/><ref name="Antileukotriene agents" />
• Oral theophyllines are sometimes used for controlling chronic asthma, but their used is minimized due to side effects.<ref name="BertrandSánchez2020" />
• 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.<ref name="BertrandSánchez2020" /><ref name="Solèr ">Template:Cite journal</ref>
• Anticholinergic medications such as ipratropium bromide have not been shown to be beneficial for treating chronic asthma in children over 2 years old,<ref>Template:Cite journal</ref> and are not suggested for routine treatment of chronic asthma in adults.<ref>Template:Cite journal</ref>
• 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).<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>
• Macrolide antibiotics, particularly the azalide macrolide azithromycin, are a recently added Global Initiative for Asthma (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.<ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref> Azithromycin's mechanism of action is not established, and could involve pathogen- and/or host-directed anti-inflammatory activities.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref><ref name="Outcomes of Antibiotics in Adults w" /> However, these groups of asthma patients have not been studied in randomized treatment trials and patient selection needs to be carefully individualized.

• A 2024 study indicates that commonly used diabetes medications may lower asthma attacks by up to 70%.<ref>Template:Cite journal</ref> The research examined metformin and GLP-1 drugs such as Ozempic (semaglutide), Mounjaro (tirzepatide), and Saxenda (liraglutide). Among nearly 13,000 participants with both diabetes and asthma, metformin reduced the risk of asthma attacks by 30%, with an additional 40% reduction when combined with a GLP-1 drug.<ref>{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref>

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.<ref>Template:Cite journal</ref> 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.<ref name=Ahm2015>Template:Cite journal</ref> Stopping LABA probably makes little or no important difference to asthma control or asthma-related quality of life.<ref name=Ahm2015/> Whether or not stopping LABA increases the risk of serious adverse events or exacerbations requiring an emergency department visit or hospitalization is uncertain.<ref name=Ahm2015/>

Delivery methods

Medications are typically provided as metered-dose inhalers (MDIs) in combination with an inhaler 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.<ref name="NHLBI07p250">Template:Harvnb</ref> 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.<ref>Template:Cite journal</ref> There is no strong evidence for the use of intravenous LABA for adults or children who have acute asthma.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

Adverse effects

Long-term use of inhaled corticosteroids at conventional doses carries a minor risk of adverse effects.<ref name=Safe09>Template:Cite journal</ref> Risks include thrush, the development of cataracts, and a slightly slowed rate of growth.<ref name=Safe09/><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Rinsing the mouth after the use of inhaled steroids can decrease the risk of thrush.<ref>Template:Cite book</ref> Higher doses of inhaled steroids may result in lower bone mineral density.<ref>Template:Cite journal</ref>

Others

Inflammation in the lungs can be estimated by the level of exhaled nitric oxide.<ref name="Petsky_2016" /><ref name="Petsky_2016_2" /> 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.<ref name="Petsky_2016">Template:Cite journal</ref><ref name="Petsky_2016_2">Template:Cite journal</ref>

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%.<ref name="BertrandSánchez2020" />
• Corticosteroids by mouth, with five days of prednisone being the same two days of dexamethasone.<ref>Template:Cite journal</ref> One review recommended a seven-day course of steroids.<ref>Template:Cite journal</ref>
• Magnesium sulfate intravenous treatment increases bronchodilation when used in addition to other treatment in moderate severe acute asthma attacks.<ref name="NHLBI07p373" /><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> In adults intravenous treatment results in a reduction of hospital admissions.<ref>Template:Cite journal</ref> Low levels of evidence suggest that inhaled (nebulized) magnesium sulfate may have a small benefit for treating acute asthma in adults.<ref name="Knightly_2017">Template:Cite journal</ref> Overall, high-quality evidence do not indicate a large benefit for combining magnesium sulfate with standard inhaled treatments for adults with asthma.<ref name="Knightly_2017" />
• Heliox, a mixture of helium and oxygen, may also be considered in severe unresponsive cases.<ref name="NHLBI07p373" />
• Intravenous salbutamol is not supported by available evidence and is thus used only in extreme cases.<ref name=rodrigo>Template:Cite journal</ref>
• Methylxanthines (such as theophylline) were once widely used, but do not add significantly to the effects of inhaled beta-agonists.<ref name=rodrigo/> Their use in acute exacerbations is controversial.<ref name="GINA_2011_page37">Template:Harvnb</ref>
• The dissociative anaesthetic 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.<ref name="NHLBI07p399">Template:Harvnb</ref> A 2012 Cochrane review found no significant benefit from the use of ketamine in severe acute asthma in children.<ref>Template:Cite journal</ref>
• For those with severe persistent asthma not controlled by inhaled corticosteroids and LABAs, bronchial thermoplasty may be an option.<ref name=Bronch10>Template:Cite journal</ref> It involves the delivery of controlled thermal energy to the airway wall during a series of bronchoscopies.<ref name=Bronch10/><ref>Template:Cite journal</ref> While it may increase exacerbation frequency in the first few months it appears to decrease the subsequent rate. Effects beyond one year are unknown.<ref name=GINA_2011_page70>Template:Harvnb</ref>
• Monoclonal antibody injections such as mepolizumab,<ref name="Mepolizumab">{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref> dupilumab,<ref name="Dupilumab">Template:Cite journal</ref> or omalizumab may be useful in those with poorly controlled atopic asthma.<ref name=NEJM2017>Template:Cite journal</ref> However, Template:As of these medications are expensive and their use is therefore reserved for those with severe symptoms to achieve cost-effectiveness.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

• Evidence suggests that sublingual immunotherapy in those with both allergic rhinitis and asthma improve outcomes.<ref name="pmid23532243">Template:Cite journal</ref>
• It is unclear if non-invasive positive pressure ventilation in children is of use as it has not been sufficiently studied.<ref>Template:Cite journal</ref>Template:Update inline

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.<ref name="Chan_2022">Template:Cite journal</ref> 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.<ref name="Chan_2022" /> 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.<ref name="Chan_2022" />

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.<ref name="blanc">Template:Cite journal</ref><ref name=shenfield>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> There is tentative support for use of vitamin C in exercise induced bronchospasm.<ref>Template:Cite journal Template:Open access</ref> Fish oil dietary supplements (marine n-3 fatty acids)<ref>Template:Cite journal</ref> and reducing dietary sodium<ref>Template:Cite journal</ref> 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.<ref name="Williamson_2023">Template:Cite journal</ref> There is no strong evidence to suggest that vitamin D supplements improve day-to-day asthma symptoms or a person's lung function.<ref name="Williamson_2023" /> There is no strong evidence to suggest that adults with asthma should avoid foods that contain monosodium glutamate (MSG).<ref name="Zhou_2012">Template:Cite journal</ref> There have not been enough high-quality studies performed to determine if children with asthma should avoid eating food that contains MSG.<ref name="Zhou_2012" />

Acupuncture is not recommended for the treatment as there is insufficient evidence to support its use.<ref name="NHLBI07p240" /><ref name="mccartney">Template:Cite journal</ref> Air ionizers show no evidence that they improve asthma symptoms or benefit lung function; this applied equally to positive and negative ion generators.<ref name="pmid22972060">Template:Cite journal</ref> Manual therapies, including osteopathic, chiropractic, physiotherapeutic and respiratory therapeutic manoeuvres, have insufficient evidence to support their use in treating asthma.<ref name="hondras">Template:Cite journal</ref> Pulmonary rehabilitation, however, may improve quality of life and functional exercise capacity when compared to usual care for adults with asthma.<ref>Template:Cite journal</ref> 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.<ref name="BGMA08" /> Thus an expert panel felt that evidence was insufficient to support its use.<ref name="NHLBI07p240">Template:Harvnb</ref> There is no clear evidence that breathing exercises are effective for treating children with asthma.<ref>Template:Cite journal</ref>

Prognosis

The prognosis for asthma is generally good, especially for children with mild disease.<ref>Template:Cite book</ref> Mortality has decreased over the last few decades due to better recognition and improvement in care.<ref name=NHLBI07p1>Template:Harvnb</ref> In 2010 the death rate was 170 per million for males and 90 per million for females.<ref name=GAR2014>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Rates vary between countries by 100-fold.<ref name=GAR2014/>

Globally it causes moderate or severe disability in 19.4 million people Template:As of (16 million of which are in low and middle income countries).<ref>Template:Cite book</ref> Of asthma diagnosed during childhood, half of cases will no longer carry the diagnosis after a decade.<ref name=El2010/> Airway remodelling is observed, but it is unknown whether these represent harmful or beneficial changes.<ref name=Maddox>Template:Cite journal</ref> More recent data find that severe asthma can result in airway remodelling and the "asthma with chronic obstructive pulmonary disease syndrome (ACOS)" that has a poor prognosis.<ref>Template:Cite journal</ref> Early treatment with corticosteroids seems to prevent or ameliorates a decline in lung function.<ref name=beckett>Template:Cite journal</ref> Asthma in children also has negative effects on quality of life of their parents.<ref>Template:Cite journal</ref>

• Asthma world map-Deaths per million persons-WHO2012.svg

  Asthma deaths per million persons in 2012Template:Div colTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:LegendTemplate:Div col end

• Asthma world map - DALY - WHO2004.svg

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Epidemiology

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}}

File:Asthma prevalence, OWID.svg

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In 2019, approximately 262 million people worldwide were affected by asthma and approximately 461,000 people died from the disease.<ref name="lancetasthma" /> Rates vary between countries with prevalences between 1 and 18%.<ref name=GINA2011p2/> It is more common in developed than developing countries.<ref name=GINA2011p2/> One thus sees lower rates in Asia, Eastern Europe and Africa.<ref name=M38/> 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.<ref name=GINA2011p2/> The reason for these differences is not well known.<ref name=GINA2011p2/> Low- and middle-income countries make up more than 80% of the mortality.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

While asthma is twice as common in boys as girls,<ref name=GINA2011p2/> severe asthma occurs at equal rates.<ref name=Bush2009>Template:Cite journal</ref> In contrast adult women have a higher rate of asthma than men<ref name=GINA2011p2/> and it is more common in the young than the old.<ref name=M38/> 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Global rates of asthma have increased significantly between the 1960s and 2008<ref name=Ana2010/><ref>Template:Cite journal</ref> with it being recognized as a major public health problem since the 1970s.<ref name=M38/> Rates of asthma have plateaued in the developed world since the mid-1990s with recent increases primarily in the developing world.<ref name="pmid16175830">Template:Cite journal</ref> Asthma affects approximately 7% of the population of the United States<ref name=Fanta2009/> and 5% of people in the United Kingdom.<ref name=Anderson2007>Template:Cite journal</ref> Canada, Australia and New Zealand have rates of about 14–15%.<ref>Template:Cite book</ref>

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.<ref>Template:Cite news</ref> Children are more likely see a physician due to asthma symptoms after school starts in September.<ref>Template:Cite news</ref>

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).<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name="Asthma as a risk factor for COPD in"/> Additional prospective population-based data indicate that ACOS seems to represent a form of severe asthma, characterized by more frequent hospitalizations, and to be the result of early-onset asthma that has progressed to fixed airflow obstruction.<ref name="Asthma, COPD and overlap syndrome" />

Health disparities

As of 2005, more "westernized," urbanized countries had much higher rates of asthma than "less developed" countries. However, exposure to urbanization alone has not been able to explain these disparities.<ref>Template:Cite journal</ref>

In the United States, the burden of asthma falls disproportionately on racial and ethnic minorities and economically underprivileged populations.<ref name="pmid34602887">Template:Cite journal</ref> As of 2016, the prevalence of asthma was highest in non-Hispanic black and Puerto Rican children. The prevalence of asthma was also over 1.5 times higher in Americans 100% below the poverty level than those 450% of the poverty level or higher.<ref>Template:Cite book</ref> As of 2021, the mortality rate for black Americans with asthma was two times higher than for white Americans.<ref name="pmid34602887"/>

Neighborhoods in the United States with predominantly racial and ethnic minority populations are affected to a greater extent than predominantly white neighborhoods by air pollutants, which are a significant factor in the occurrence of asthma. Additionally, residents of areas that were more likely to be redlined have asthma emergency department visit rates 2.4 times higher than residents of areas that were less likely to be redlined.<ref name="pmid34602887"/>

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.<ref name=USEco2014>Template:Cite journal</ref> 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.<ref name=USEco2014/> 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.<ref name=USEco2014/>

History

File:C14 Chinese medication chart; Asthma etc. Wellcome L0039608.jpg

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.<ref name="Manniche1999" /> 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.<ref name="M38" /> In 200 BC it was believed to be at least partly related to the emotions.<ref name="Andrew2010" /> 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.<ref>Template:Cite journal</ref> Traditional Chinese medicine also offered medication for asthma, as indicated by a surviving 14th-century manuscript curated by the Wellcome Foundation.<ref>C14 Chinese medication chart; Asthma etc. Wellcome L0039608</ref>

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.<ref name="pmid20747287">Template:Cite journal</ref><ref name="pmid20746575">Template:Cite journal</ref> Medical treatment in 1880 included the use of intravenous doses of a drug called pilocarpine.<ref name="pmid20749537">Template:Cite journal
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In 1886, F. H. Bosworth theorized a connection between asthma and hay fever.<ref name="pmid21407325">Template:Cite journal</ref>

At the beginning of the 20th century, the focus was the avoidance of allergens as well as the use of selective beta-2 adrenoceptor agonists as treatment strategies.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Epinephrine was first referred to in the treatment of asthma in 1905.<ref name="pmid18733372">Template:Cite journal</ref> Oral corticosteroids began to be used for the condition in 1950. The use of a pressurized metered-dose inhaler was developed in the mid-1950s for the administration of adrenaline and isoproterenol and was later used as a beta₂-adrenergic agonist.

Inhaled corticosteroids and selective short-acting beta agonists came into wide use in the 1960s.<ref name="pmid22375974">Template:Cite journal</ref><ref name="pmid17092772">Template:Cite journal</ref>

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.<ref>Template:Cite book</ref>

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.<ref name="pmid16185365" /> 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.<ref name="pmid16185365">Template:Cite journal</ref>

Between 1970 and 1985, the following countries saw a general rise in reported asthma mortality in people aged 5 to 34: Singapore, Australia, Japan, England/Wales, West Germany, Israel, United States, Netherlands, Canada, and France. Additionally, New Zealand experienced a major epidemic of asthma in this period, which may have been due to inadequate maintenance therapy and long-term management of the disease amongst those affected, as well as delays in receiving care in emergencies.<ref name="pmid3180894">Template:Cite journal</ref>

In January 2021, an appeal court in France overturned a deportation order against a 40-year-old Bangladeshi man, who was a patient with 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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

References

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External links

• WHO fact sheet on asthma