Asthma

Asthma is a common long-term inflammatory disease of the airways. It is characterized by variable and recurring symptoms and reduced lung function. Symptoms include episodes of wheezing, coughing, chest tightness, and shortness of breath. 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. Depending on the person, asthma symptoms may become worse at night or with exercise.

Asthma is thought to be caused by a combination of genetic and environmental factors. Environmental factors include exposure to air pollution and allergens. Other potential triggers include medications such as aspirin and beta blockers. Diagnosis is usually based on the pattern of symptoms, response to therapy over time, and spirometry lung function testing. Asthma is classified according to the amount of medication required to control symptoms or mechanisms underlying the condition.

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

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

Signs and symptoms

Asthma is characterized by recurrent episodes symptoms of wheezing, shortness of breath, chest tightness, and coughing. Symptoms are usually worse at night and in the early morning or in response to exercise or cold air.Template:Rp Some people with asthma rarely experience symptoms, usually in response to triggers, whereas others may react frequently and readily and experience persistent symptoms.Template:Rp

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. Psychological disorders are also more common, with anxiety disorders occurring in between 16 and 52% and mood disorders in 14–41%. It is not known whether asthma causes psychological problems or psychological problems lead to asthma. Current asthma, but not former asthma, is associated with increased all-cause mortality, heart disease mortality, and chronic lower respiratory tract disease mortality. Asthma, particularly severe asthma, is strongly associated with development of chronic obstructive pulmonary disease (COPD) as found in Asthma-COPD Overlap. Those with asthma, especially if it is poorly controlled, are at increased risk for radiocontrast reactions.

Classification

Due to the diversity in onset, symptoms, outcomes, and response to treatment, asthma is often considered a syndrome — a collection of signs and symptoms — rather than one single condition. Historically asthma was classified as caused by external factors such as allergens (extrinsic) or by internal factors, unrelated to allergies (intrinsic). Currently asthma is most commonly classified according to severity, control of symptoms, phenotypes and endotypes.

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. 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. In contrast to emphysema, asthma affects the bronchi, not the alveoli. 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.

Asthma exacerbation

Severity of an acute exacerbationTemplate:Rp

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 asthma exacerbation, commonly referred to as an asthma attack, are episodes of increased symptoms (shortness of breath, wheezing, coughing, chest tightness), and decreased lung function.Template:Rp

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. A blue colour of the skin and nails may occur from lack of oxygen.

The level of peak expiratory flow rate (PEFR) is determined as follows:

• A mild exacerbation is ≥200 L/min, or ≥50% of the predicted best.
• Moderate is defined as between 80 and 200 L/min, or 25% and 50% of the predicted best.
• Severe is defined as ≤ 80 L/min, or ≤25% of the predicted best.

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

Brittle asthma is a kind of asthma distinguishable by recurrent, severe attacks. However brittle asthma is best regarded as a historical disease descriptor rather than a distinct diagnostic category. While it remains useful for understanding older literature it is no linger routinely used in contemporary clinical practice.

Phenotyping and endotyping

A phenotype is the way in which a condition presents itself, such as when the disease first starts to affect a person and what symptoms an individual displays. An endotype is the mechanisms that underlie the condition. Asthma is most commonly divided into two endotypes, T2-high and T2-low (non-T2). Within the two main endotypes there are subpopulations (phenotypes), some of which overlap or can be categorized under both of the two endotypes.

The two endotypes are distinguished based on the type of inflammation present, with the type-2 high endotype involving the type 2 immune system response and type-2 low involving type 1 immune system response. Type-2 high is characterized by increased eosinophils, increased Fractional exhaled nitric oxide (FeNO), or allergens. Type-2 low asthma is the absence of these inflammatory markers and the mechanisms are not well researched. The phenotypes included under the type-2 high endotype include early-onset allergic asthma, late-onset eosinophilic asthma, and Aspirin-exacerbated respiratory disease. Type-2 low asthma phenotypes include asthma associated with obesity, neutrophilic asthma, asthma associated with cigarette smoke, and paucigranulocytic asthma. Occupational asthma can be further split into separate phenotypes, irritant-induced asthma — caused by exposure to airway irritants such as cleaning products and dust — and sensitizer-induced occupational asthma — developed hypersensitivity. Irritant-induced asthma is a type-2 low phenotype while sensitizer-induced occupational asthma is a type-2 high phenotype. Asthma-COPD overlap (ACO) currently lacks a consistent definition making it hard to categorize it into either endotype.

Exercise-induced

Exercise can trigger bronchoconstriction both in people with and without asthma. It occurs in most people with asthma and up to 20% of people without asthma. Exercise-induced bronchoconstriction is common in professional athletes. The highest rates are among cyclists (up to 45%), swimmers, and cross-country skiers. Asthma symptoms may occur under a wide range of weather conditions but are more frequently triggered by changes in weather.Template:Rp Inhaled beta₂ agonists do not appear to improve athletic performance among those without asthma; however, oral doses may improve endurance and strength.

Alcohol-induced asthma

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

Infectious asthma

Infectious asthma is an easily identified clinical presentation. 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, or as "asthma associated with infection" (AAWI) 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 to 70% in a specialty practice treating mainly severe asthma patients.

Causes

Asthma is caused by a combination of complex and incompletely understood environmental and genetic interactions. These influence both its severity and its responsiveness to treatment. 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. 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.

Environmental

Many environmental factors have been associated with the development and exacerbation of asthma, including allergens, air pollution, and other environmental chemicals. 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, and moulds. Smoking during pregnancy and after delivery is associated with a greater risk of asthma-like symptoms.Template:Rp Low air quality from environmental factors such as traffic pollution or high ozone levelsTemplate:Rp has been associated with both asthma development and increased asthma severity. Over half of cases in children in the United States occur in areas when air quality is below the EPA standards. Low air quality is more common in low-income and minority communities.

Exposure to indoor volatile organic compounds may be a trigger for asthma; formaldehyde exposure, for example, has a positive association. Phthalates in certain types of PVC are associated with asthma in both children and adults. While exposure to pesticides is linked to the development of asthma, a cause and effect relationship has yet to be established. 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.

Pregnancy

Maternal psychological stress during pregnancy is a risk factor for the child to develop asthma.

Allergens

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

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. 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. Exposure to bacterial endotoxin in early childhood may prevent the development of asthma, but exposure at an older age may provoke bronchoconstriction. Evidence supporting the hygiene hypothesis includes lower rates of asthma on farms and in households with pets.

Use of antibiotics in early life had been linked to the development of asthma. A later review found that previous studies came to inconsistent conclusions on the relationship between antibiotic use and asthma development, and that many failed to rule out respiratory infections as a confounding factor.

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. 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.

Genetic

Asthma is highly polygenic, with hundreds of common and rare genetic variants of small effect contributing to disease susceptibility, age of onset, and inflammatory phenotypes. Twin studies and family studies support a substantial heritable component, with estimates that roughly half or more of asthma susceptibility is explained by genetics that is further modulated by environmental and epigenetic factors. Large genome-wide association studies (GWAS) and sequencing efforts indicate that risk reflects the cumulative effects of numerous common genetic variants together with a more limited contribution from rare variants, rather than a small number of loci of large effect.

Meta-analyses now report over 200 genome-wide significant susceptibility loci, many mapping to immune and epithelial genes and explaining a measurable, though still incomplete, fraction of heritability. Pathway analyses consistently highlight type 2 inflammation, epithelial barrier function, and both innate and adaptive immune signalling, including loci near or within IL33, IL1RL1/IL18R1, TSLP, MHC class II, and GATA3. The chromosome region 17q12–21 remains the most robustly replicated asthma locus, with effects strongest for childhood-onset disease. Multiple genes in this region, including ORMDL3 and GSDMB, appear to act primarily through regulatory mechanisms, with gene-environment interactions and age-dependent effects on airway epithelial responses, particularly to early-life viral infections.

Genetic correlation analyses demonstrate substantial overlap between asthma and other atopic disorders such as eczema and allergic rhinitis, as well as with lung function traits. Multi-trait studies identify shared risk genes across asthma, hay fever, and eczema, supporting partially common pathways involving type 2 immunity and epithelial barrier dysfunction. Consistent with this architecture, polygenic risk scores (PRS) derived from multi-ancestry GWAS can stratify individuals by asthma risk, with higher predictive performance for childhood-onset than adult-onset disease. Individuals in the highest PRS percentiles show several-fold increased odds of childhood asthma, and PRS analyses have helped delineate heterogeneity across asthma–COPD overlap and related comorbid traits, although clinical implementation remains investigational.

Many asthma-associated variants act within regulatory elements, with effects that are highly cell-type specific and modulated by environmental exposures such as allergens, air pollution, and respiratory infections. Integrative genomic and epigenomic studies show enrichment of risk alleles in enhancers active in airway epithelial and immune cells, and indicate that DNA methylation and other epigenetic modifications mediate part of the gene-environment interaction underlying asthma susceptibility and phenotypic heterogeneity.

Medical conditions

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

There is a correlation between obesity and the risk of asthma, with both having increased in recent years. 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.

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

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. Most individuals can develop severe exacerbation from a number of triggering agents.

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

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.

Pathophysiology

File:Asthma attack-illustration NIH.jpg

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.

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.Template:Rp 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.Template:Rp 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 number 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.

Diagnosis

Asthma is defined by the Global Initiative for Asthma as:Template:Rp

... a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms, such as wheeze, shortness of breath, chest tightness and cough, that vary over time and in intensity, together with variable expiratory airflow. Airflow limitation may later become persistent.

There is currently no precise test for the diagnosis, which is typically based on the pattern of symptoms and response to therapy over time. 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. Spirometry is then used to confirm the diagnosis. In children under the age of six, the diagnosis is more difficult as they are too young for spirometry.Template:Rp

Spirometry

Spirometry, which measures the lung function in terms of the amount and speed of air as it is exhaled and inhaled, is recommended to aid in diagnosis and management.Template:RpTemplate:Rp 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. As caffeine is a bronchodilator in people with asthma, the use of caffeine before a lung function test may interfere with the results. Single-breath diffusing capacity can help differentiate asthma from COPD. It is reasonable to perform spirometry every one or two years to follow how well a person's asthma is controlled.

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.

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.

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.

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. Bronchiolitis and other viral infections may also produce wheezing. 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. 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.

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. 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.

Prevention

Currently, the only methods of preventing asthma that have been endorsed by clinical guidelines are avoiding the use of broad-spectrum antibiotics in the first year of a child life, eliminating exposure to tobacco smoke both in utero and following birth, appropriate assessment and treatment of vitamin D deficiency during pregnancy, and vaginal birthing when possible.Template:Rp Other proposed preventative measures such as dietary changes, breastfeeding, supplements, and early exposure to pets or other common allergens do not currently have enough evidence to support their effectiveness.Template:Rp

Management

The goal of asthma management is to reduce symptoms minimize the risk of complication such as exacerbations, reduced lung functioning, and medication side effects.Template:Rp This is done by evaluating asthma control and the risk of exacerbation, providing education and guidance on how to manage the disease, finding triggers and ways to minimize them, and medication. Asthma control should be reviewed during doctors appointments so that treatment can be adjusted accordingly.Template:RpTemplate:Rp

After a diagnosis of asthma is made the person receiving the diagnosis and their family should receive education about the disease and a plan for management. Education includes information about avoiding triggers, self monitoring of symptoms or peak expiratory flow, an asthma action plan, asthma control and treatment options.Template:RpTemplate:Rp Asthma action plans include management options to prevent and treat exacerbations as well as how to modify treatment based on symptoms or seek additional medical care. Template:Rp School based education programs on how to manage asthma decrease hospitalizations for asthma in school-aged children.Template:Rp

Medications for asthma are generally divided into three categories, controllers — taken daily to control symptoms, reduce exacerbations and decrease inflammation — relievers — taken as needed for severe symptoms or exacerbations — and additional medications added on to manage more severe asthma.Template:Rp Medications are prescribed at the lowest dose possible while still treating symptoms and preventing exacerbations.

Lifestyle modification

Non-medical strategies to manage asthma consist of avoiding exposure to triggers and management of factors that contribute to asthma severity or symptoms. Exposure to cigarette smoke, from smoking or second-hand smoke, negatively affects asthma control and it is therefore recommended for those with asthma to refrain from smoking and limit exposure to second-hand smoke.Template:Rp For those with occupational asthma, it is recommended that sensitizers and allergens at work be avoided.Template:Rp Due to the variety of potential allergens and the difficulty of eliminating exposure to allergens, current guidelines do not recommend that those with asthma avoid indoor or outdoor allergens.Template:Rp Certain medications such as Aspirin, beta-blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs) can worsen asthma symptoms in some individuals. It is still considered safe for those with asthma to take these medications, unless they have caused adverse reactions in the past.Template:Rp

Guidelines encourage those with asthma to maintain a balanced and healthy diet due to benefits on overall wellbeing. Regular physical activity is encouraged for those with asthma due to its positive effects on overall health, however, it does not result in any direct improvement in asthma symptoms and no specific form of exercise is more beneficial. For some, exercise may trigger asthma symptoms and therefore it is recommended that inhalers be used beforehand. Pulmonary rehabilitation may be used to increase tolerance to exercise. Obesity can cause asthma symptoms to be harder to control or cause more severe symptoms, weight loss in obese individuals is therefore recommended.Template:Rp

There is not enough evidence that dietary changes, including restrictive diets or supplements are helpful in managing asthma. Alternative treatments such as acupuncture, air ionizers, manual therapies (osteopathic, chiropractic, physiotherapeutic and respiratory therapeutic manoeuvres), and breathing exercises are not recommended by clinical guidelines due to a lack of evidence that they are effective. Breathing exercises do not decrease asthma exacerbations or improve lung functioning, however they can be used alongside medications to help control symptoms.Template:Rp

Medications

Devices for inhaled medications include pressurized metered dose inhaler (pMDI), dry-powder inhalers (DPI), mist inhalers and nebulizers. The choice of delivery method depends on the type of medication used, local availability, age, and ability to use the inhaler properly.Template:Rp DPIs are difficult for children to use and are therefore discouraged in those under six years of age. Spacers are used alongside pMDIs to increase the amount of medication inhaled.

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. Antibiotics are generally not needed for sudden worsening of symptoms or for treating asthma at any time.

Medications for asthma exacerbations

A round canister above a blue plastic holder

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.Template:Rp They are recommended before exercise in those with exercise-induced symptoms.
• 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.Template:Rp Anticholinergic bronchodilators can also be used if a person cannot tolerate a SABA. 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. 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.
• Older, less selective adrenergic agonists, such as inhaled epinephrine, have similar efficacy to SABAs. They are, however, not recommended due to concerns regarding excessive cardiac stimulation.
• 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. For adults and children who are in the hospital due to acute asthma, systemic (IV) corticosteroids improve symptoms. A short course of corticosteroids after an acute asthma exacerbation may help prevent relapses and reduce hospitalizations.
• Other remedies, less established, are intravenous or nebulized magnesium sulfate and helium mixed with oxygen. Aminophylline could be used with caution as well.
• Mechanical ventilation is the last resort in case of severe hypoxemia.
• Intravenous administration of the drug aminophylline does not provide an improvement in bronchodilation when compared to standard inhaled beta₂ agonist treatment. Aminophylline treatment is associated with more adverse effects compared to inhaled beta₂ agonist treatment.

Long–term control

A round canister above an orange plastic holder

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

• Corticosteroids are generally considered the most effective treatment available for long-term control. Inhaled forms are usually used except in the case of severe persistent disease, in which oral corticosteroids may be needed. Dosage depends on the severity of symptoms. High dosage and long-term use may lead to side effects such as growth delay, adrenal suppression, and osteoporosis. Continuous (daily) use of an inhaled corticosteroid, rather than intermitted use, seems to provide better results in controlling asthma exacerbations. Commonly used corticosteroids are budesonide, fluticasone, mometasone and ciclesonide.
• Long-acting beta-adrenoceptor agonists (LABA) such as salmeterol and formoterol can improve asthma control in adults, when given in combination with inhaled corticosteroids. In children this benefit is uncertain. When used without steroids they increase the risk of severe side-effects, and with corticosteroids they may slightly increase the risk. 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. Children who require LABA as part of their asthma treatment may need to go to the hospital more frequently.
• 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. For adults or adolescents who have persistent asthma that is not well controlled, the addition of anti-leukotriene agents along with daily inhaled corticosteriods improves lung function and reduces the risk of moderate and severe asthma exacerbations. 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. In those under five years of age, anti-leukotriene agents were the preferred add-on therapy after inhaled corticosteroids. A 2013 Cochrane systematic review concluded that anti-leukotriene agents appear to be of little benefit when added to inhaled steroids for treating children. 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. since 2013Template:Dated maintenance category (articles) there is one medication in this family known as zileuton.
• Mast cell stabilizers (such as cromolyn sodium) are safe alternatives to corticosteroids but not preferred because they have to be administered frequently.
• Oral theophyllines are sometimes used for controlling chronic asthma, but their use is minimized due to side effects.
• 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 in allergic asthma.
• Anticholinergic medications such as ipratropium bromide are not beneficial for treating chronic asthma in children over 2 years old, and are not suggested for routine treatment of chronic asthma in adults.
• Macrolide antibiotics, particularly the azalide macrolide azithromycin, are a 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. Azithromycin's mechanism of action is not established, and could involve pathogen- and/or host-directed anti-inflammatory activities. 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. 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 that 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. 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. Stopping LABA probably makes little or no important difference to asthma control or asthma-related quality of life. Whether or not stopping LABA increases the risk of serious adverse events or exacerbations requiring an emergency department visit or hospitalization is uncertain.

Depemokimab (Exdensur) was approved for medical use in both the United Kingdom and United States in December 2025.

Others

Inflammation in the lungs can be estimated by the level of exhaled nitric oxide. 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.

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

• Humidified oxygen to alleviate hypoxia if saturations fall below 92%.
• Corticosteroids by mouth, with five days of prednisone being the same two days of dexamethasone. One review recommended a seven-day course of steroids.
• Magnesium sulfate intravenous treatment increases bronchodilation when used in addition to other treatment in moderate to severe acute asthma attacks.Template:Rp In adults, intravenous treatment results in a reduction of hospital admissions. Low levels of evidence suggest that inhaled (nebulized) magnesium sulfate may have a small benefit for treating acute asthma in adults. Overall, high-quality evidence do not indicate a large benefit for combining magnesium sulfate with standard inhaled treatments for adults with asthma.
• Heliox, a mixture of helium and oxygen, may also be considered in severe unresponsive cases.Template:Rp
• Intravenous salbutamol is not supported by available evidence and is thus used only in extreme cases.
• Methylxanthines, such as theophylline, were previously widely used in asthma management but provide little additional benefit over inhaled β-agonists and are no longer recommended, particularly in acute exacerbations, because of limited efficacy and safety concerns.Template:Rp
• For those with severe, persistent asthma not controlled by inhaled corticosteroids and LABAs, bronchial thermoplasty may be an option. It involves the delivery of controlled thermal energy to the airway wall during a series of bronchoscopies. Bronchial thermoplasty may be associated with an increase in asthma exacerbations and respiratory adverse events in the period immediately following treatment; evidence for longer-term benefit is limited, and the durability of effects beyond the first year remains uncertain.Template:Rp
• Monoclonal antibody injections such as mepolizumab, dupilumab, or omalizumab may be useful in those with poorly controlled atopic asthma. However, since 2019Template:Dated maintenance category (articles) these medications are expensive and their use is therefore reserved for those with severe symptoms to achieve cost-effectiveness. 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.
• Evidence suggests that sublingual immunotherapy in those with both allergic rhinitis and asthma improve outcomes.
• It is unclear if non-invasive positive pressure ventilation in children is of use, as it has not been sufficiently studied.

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. 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. 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.

Prognosis

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

Globally, it causes moderate or severe disability in 19.4 million people since 2004Template:Dated maintenance category (articles) (16 million of which are in low and middle-income countries). Of asthma diagnosed during childhood, half of the cases will no longer carry the diagnosis after a decade. Airway remodelling is observed, but it is unknown whether these represent harmful or beneficial changes. 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. Early treatment with corticosteroids seems to prevent or ameliorate a decline in lung function. Asthma in children also has negative effects on the quality of life of their parents.

• Asthma deaths per million persons in 2012 Script error: No such module "Check for unknown parameters".   0–10   11–13   14–17   18–23   24–32   33–43   44–50   51–66   67–95   96–251
  Asthma deaths per million persons in 2012

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  Disability-adjusted life year for asthma per 100,000 inhabitants in 2004

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Epidemiology

In 2019, approximately 262 million people worldwide were affected by asthma, and approximately 461,000 people died from the disease. Rates vary between countries, with prevalences between 1 and 29%.Template:Rp It is more common in developed than developing countries.Template:Rp One thus sees lower rates in Asia, Eastern Europe, and Africa. 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.Template:Rp The reasons for these differences are unclear.Template:Rp Low- and middle-income countries make up more than 80% of the mortality.

While asthma is twice as common in boys as girls,Template:Rp severe asthma occurs at equal rates. In contrast adult women have a higher rate of asthma than menTemplate:Rp and it is more common in the young than the old. 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.

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

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. Children are more likely see a physician due to asthma symptoms after school starts in September.

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). 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.

Health disparities

since 2005Template:Dated maintenance category (articles), 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.

In the United States, the burden of asthma falls disproportionately on racial and ethnic minorities and economically underprivileged populations. since 2016Template:Dated maintenance category (articles), 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. since 2021Template:Dated maintenance category (articles), the mortality rate for black Americans with asthma was two times higher than for white Americans.

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.

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. 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. Among both children and adults in the lowest-income communities in the United States, there was a higher rate of hospital stays for asthma in 2010 than in the highest-income communities.

History

Asthma was recognized in ancient Egypt and was treated by drinking an incense mixture known as kyphi. It was officially named as a specific respiratory problem by Hippocrates c. Template:Trim, with the Greek word for "panting" forming the basis of our modern name. In 200 BC, it was believed to be at least partly related to the emotions. In the 12th century, the Jewish physician and philosopher Maimonides wrote ("Treatise on Asthma") in Arabic. In the work, he described the symptoms of asthma, proposed dietary and therapeutic treatments, and emphasized the importance of clean air and climate in managing the condition. Traditional Chinese medicine also offered medication for asthma, as indicated by a surviving 14th-century manuscript curated by the Wellcome Foundation.

19th century

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.

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. Medical treatment in 1880 included the use of intravenous doses of a drug called pilocarpine.

In 1886, F. H. Bosworth theorized a connection between asthma and hay fever.

20th century

File:Grimaults cigarette ad.jpg

1907 advertisement for Grimault's Indian Cigarettes, promoted as a means of relieving asthma. They contained belladonna and cannabis.

At the beginning of the 20th century, the focus was on the avoidance of allergens as well as the use of selective beta₂-adrenergic agonists as treatment strategies.

Early 1900s

Epinephrine (adrenaline) was first referred to in the treatment of asthma in 1905. The asthma was relived with this treatment by what was described as "vasomotor ataxia of the relaxing variety". The successful results of using epinephrine provided encouraging medical data on the vasodilator hypothesis, that asthma was due to vasodilation and the subsequent inflammation of the swelling of the bronchial mucosa.

1930s–1950s

In the 1930s, U.S. physician Alvin Barach created, by means of spirometry, the quantification of expiratory flow rates to nebulized epinephrine for those with asthma, which was the first published medical report on the effectiveness of bronchodilation.

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. 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.

1940s–1960s

In the 1940s, the first pure β-agonist to be synthesized was isoprenaline. Both isoprenaline and adrenaline are catecholamines. However, isoprenaline was an effective bronchodilator that was more selective than epinephrine.

The efficacy of anecdotal applications of oral corticosteroids (OCS) for the asthma was published in 1952. In 1958, the association between a treatment strategy of OCS and a reduction in eosinophils in the sputum was published.

The use of a pressurized metered dose inhaler was developed in the mid-1950s for the administration of adrenaline as well as 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. In 1967, adrenergic receptors were classified into the two subtypes of the β₁ and the β₂ adrenergic receptors. The β₂ adrenergic receptors were found to be dominant in the lungs as well as present in the alveolar airspace. The discovery of the β₂ adrenergic receptors allowed for the discovery and development of beta2 agonists. Specifically, it allowed for the development of selective β2-agonists starting in the 1960s.

Global mortality rates

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.

External links

• WHO fact sheet on asthma