Asthma
Classification and external resources
Peak flow meters are used to measure one's peak expiratory flow rate
ICD-10	J45
ICD-9	493
OMIM	600807
DiseasesDB	1006
MedlinePlus	000141
eMedicine	article/806890
MeSH	D001249

Asthma (from the Greek άσθμα, ásthma, "panting") is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm.^[1] Symptoms include wheezing, coughing, chest tightness, and shortness of breath.^[2] Asthma is clinically classified according to the frequency of symptoms, forced expiratory volume in 1 second (FEV1), and peak expiratory flow rate.^[3] Asthma may also be classified as atopic (extrinsic) or non-atopic (intrinsic).^[4]

It is thought to be caused by a combination of genetic and environmental factors.^[5] Treatment of acute symptoms is usually with an inhaled short-acting beta-2 agonist (such as salbutamol).^[6] Symptoms can be prevented by avoiding triggers, such as allergens^[7] and irritants, and by inhaling corticosteroids.^[8] Leukotriene antagonists are less effective than corticosteroids and thus less preferred.^[9]

Its diagnosis is usually made based on the pattern of symptoms and/or response to therapy over time.^[10] The prevalence of asthma has increased significantly since the 1970s. As of 2010, 300 million people were affected worldwide.^[11] In 2009 asthma caused 250,000 deaths globally.^[12] Despite this, with proper control of asthma with step down therapy, prognosis is generally good.^[13]

Classification[link]

Asthma 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 hyperresponsiveness 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".^[14]

Asthma is clinically classified according to the frequency of symptoms, forced expiratory volume in 1 second (FEV₁), and peak expiratory flow rate.^[3] 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).^[4]

While asthma is classified based on severity, at the moment there is no clear method for classifying different subgroups of asthma beyond this system.^[16] Finding ways to identify subgroups that respond well to different types of treatments is a current critical goal of asthma research.^[16]

Although asthma is a chronic obstructive condition, it is not considered as a part of chronic obstructive pulmonary disease as this term refers specifically to combinations of disease that are irreversible such as bronchiectasis, chronic bronchitis, and emphysema.^[15] Unlike these diseases, the airway obstruction in asthma is usually reversible; however, if left untreated, the chronic inflammation from asthma can lead the lungs to become irreversibly obstructed due to airway remodeling.^[17] In contrast to emphysema, asthma affects the bronchi, not the alveoli.^[18]

Brittle asthma[link]

Brittle asthma is a term used to describe two types of asthma, distinguishable by recurrent, severe attacks.^[19] Type 1 brittle asthma refers to disease with wide peak flow variability, despite intense medication. Type 2 brittle asthma describes background well-controlled asthma, with sudden severe exacerbations.^[19]

Asthma attack[link]

An acute asthma exacerbation is commonly referred to as an asthma attack. The classic symptoms are shortness of breath, wheezing, and chest tightness.^[20] While these are the primary symptoms of asthma,^[21] some people present primarily with coughing, and in severe cases, air motion may be significantly impaired such that no wheezing is heard.^[19]

Signs which occur during an asthma attack include the use of accessory muscles of respiration (sternocleidomastoid and scalene muscles of the neck), there may be a paradoxical pulse (a pulse that is weaker during inhalation and stronger during exhalation), and over-inflation of the chest.^[22] A blue color of the skin and nails may occur from lack of oxygen.^[23]

In a mild exacerbation the peak expiratory flow rate (PEFR) is ≥200 L/min or ≥50% of the predicted best.^[24] 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.^[24]

Status asthmaticus[link]

Status asthmaticus is an acute exacerbation of asthma that does not respond to standard treatments of bronchodilators and steroids. Nonselective beta blockers (such as Timolol) have caused fatal status asthmaticus.^[25]

Exercise-induced[link]

A diagnosis of asthma is common among top athletes. One survey of participants in the 1996 Summer Olympic Games, in Atlanta, Georgia, U.S., showed that 15% had been diagnosed with asthma, and that 10% were on asthma medication.^[26]

There appears to be a relatively high incidence of asthma in sports such as cycling, mountain biking, and long-distance running, and a relatively lower incidence in weightlifting and diving. It is unclear how much of these disparities are from the effects of training in the sport.^[26][27]

Exercise-induced asthma can be treated with the use of a short-acting beta2 agonist.^[15]

Occupational[link]

Asthma as a result of (or worsened by) workplace exposures is a commonly reported occupational respiratory disease. Still most cases of occupational asthma are not reported or are not recognized as such. Estimates by the American Thoracic Society (2004) suggest that 15–23% of new-onset asthma cases in adults are work related.^[28] In one study monitoring workplace asthma by occupation, the highest percentage of cases occurred among operators, fabricators, and laborers (32.9%), followed by managerial and professional specialists (20.2%), and in technical, sales, and administrative support jobs (19.2%). Most cases were associated with the manufacturing (41.4%) and services (34.2%) industries.^[28] Animal proteins, enzymes, flour, natural rubber latex, and certain reactive chemicals are commonly associated with work-related asthma. When recognized, these hazards can be mitigated, dropping the risk of disease.^[29]

Signs and symptoms[link]

	Wheezing The sound of wheezing as heard with a stethoscope.
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Common symptoms of asthma include wheezing, shortness of breath, chest tightness and coughing, and use of accessory muscle. Symptoms are often worse at night or in the early morning, or in response to exercise or cold air.^[30] Some people with asthma only rarely experience symptoms, usually in response to triggers, whereas other may have marked persistent airflow obstruction.^[31]

Gastro-esophageal reflux disease[link]

Gastro-esophageal reflux disease coexists with asthma in 80% of people with asthma, with similar symptoms. Various theories say that asthma could facilitate GERD and/or viceversa. The first case could be due to the effect of change in thoracic pressures, use of antiasthma drugs, could facilitate the passage of the gastric content back into the oesophagus by increasing abdominal pressure or decreasing the lower esophageal sphincter. The second by promoting bronchoconstriction and irritation by chronic acid aspiration, vagally mediated reflexes and others factors that increase bronchial responsiveness and irritation.^[32]

[edit] Sleep disorders

Due to altered anatomy of the respiratory tract: increased upper airway adipose deposition, altered pharynx skeletal morphology, and extension of the pharyngeal airway; leading to upper airway collapse.^[33]

Causes[link]

Asthma is caused by environmental and genetic factors.^[5] These factors influence how severe asthma is and how well it responds to medication.^[34] The interaction is complex and not fully understood.^[35]

Studying the prevalence of asthma and related diseases such as eczema and hay fever have yielded important clues about some key risk factors.^[36] The strongest risk factor for developing asthma is a history of atopic disease;^[37] this increases one's risk of hay fever by up to 5× and the risk of asthma by 3–4×.^[38] In children between the ages of 3–14, a positive skin test for allergies and an increase in immunoglobulin E increases the chance of having asthma.^[39] In adults, the more allergens one reacts positively to in a skin test, the higher the odds of having asthma.^[40]

Because much allergic asthma is associated with sensitivity to indoor allergens and because Western styles of housing favor greater exposure to indoor allergens, much attention has focused on increased exposure to these allergens in infancy and early childhood as a primary cause of the rise in asthma.^[41][42] Primary prevention studies aimed at the aggressive reduction of airborne allergens in a home with infants have shown mixed findings. Strict reduction of dust mite allergens, for example, reduces the risk of allergic sensitization to dust mites, and modestly reduces the risk of developing asthma up until the age of 8 years old.^{[43][44][45][46]} However, studies also showed that the effects of exposure to cat and dog allergens worked in the converse fashion; exposure during the first year of life was found to reduce the risk of allergic sensitization and of developing asthma later in life.^[47][48][49]

The inconsistency of this data has inspired research into other facets of Western society and their impact upon the prevalence of asthma. One subject that appears to show a strong correlation is the development of asthma and obesity. In the United Kingdom and United States, the rise in asthma prevalence has echoed an almost epidemic rise in the prevalence of obesity.^{[50][51][52][53]} In Taiwan, symptoms of allergies and airway hyper-reactivity increased in correlation with each 20% increase in body-mass index.^[54] Several factors associated with obesity may play a role in the pathogenesis of asthma, including decreased respiratory function due to a buildup of adipose tissue (fat) and the fact that adipose tissue leads to a pro-inflammatory state, which has been associated with non-eosinophilic asthma.^[55]

Asthma has been associated with Churg–Strauss syndrome, and individuals with immunologically mediated urticaria may also experience systemic symptoms with generalized urticaria, rhino-conjunctivitis, orolaryngeal and gastrointestinal symptoms, asthma, and, at worst, anaphylaxis.^[56] Additionally, adult-onset asthma has been associated with periocular xanthogranulomas.^[57]

Environmental[link]

Many environmental risk factors have been associated with asthma development and morbidity in children. Recent studies show a relationship between exposure to air pollutants (e.g. from traffic) and childhood asthma.^[58] This research finds that both the occurrence of the disease and exacerbation of childhood asthma are affected by outdoor air pollutants. High levels of endotoxin exposure may contribute to asthma risk.^[59]

Viral respiratory infections are not only one of the leading triggers of an exacerbation but may increase one's risk of developing asthma especially in young children.^[15][37]

Respiratory infections such as rhinovirus, Chlamydia pneumoniae and Bordetella pertussis are correlated with asthma exacerbations.^[60]

Psychological stress has long been suspected of being an asthma trigger, but only in recent decades has convincing scientific evidence substantiated this hypothesis. Rather than stress directly causing the asthma symptoms, it is thought that stress modulates the immune system to increase the magnitude of the airway inflammatory response to allergens and irritants.^[61][62]

Beta blocker medications such as metoprolol may trigger asthma in those who are susceptible.^[63]

Tobacco[link]

Maternal tobacco smoking during pregnancy and after delivery is associated with a greater risk of asthma-like symptoms, wheezing, and respiratory infections during childhood.^[64] Low air quality, from traffic pollution or high ozone levels,^[65] has been repeatedly associated with increased asthma morbidity and has a suggested association with asthma development that needs further research.^[61][66]

Hygiene hypothesis[link]

One theory for the cause of the increase in asthma prevalence worldwide is the "hygiene hypothesis"^[15] —that the rise in the prevalence of allergies and asthma is a direct and unintended result of reduced exposure to a wide variety of different bacteria and virus types in modern societies, or modern hygienic practices preventing childhood infections.^[67]Children living in less hygienic environments (East Germany vs. West Germany,^[68] families with many children,^[69][70][71] day care environments^[72]) tend to have lower incidences of asthma and allergic diseases. This seems to run counter to the logic that viruses are often causative agents in exacerbation of asthma.^[73][74][75]Additionally, other studies have shown that viral infections of the lower airway may in some cases induce asthma, as a history of bronchiolitis or croup in early childhood is a predictor of asthma risk in later life.^[76] Studies which show that upper respiratory tract infections are protective against asthma risk also tend to show that lower respiratory tract infections conversely tend to increase the risk of asthma.^[77]

Antibiotic use early in life has been linked to development of asthma^[78] in several examples; it is thought that antibiotics make children who are predisposed to atopic immune responses susceptible to development of asthma because they modify gut flora, and thus the immune system (as described by the hygiene hypothesis).^[79] The hygiene hypothesis is a hypothesis about the cause of asthma and other allergic disease, and is supported by epidemiologic data for asthma.^[80] All of these things may negatively affect exposure to beneficial bacteria and other immune system modulators that are important during development, and thus may cause an increased risk for asthma and allergy.

Caesarean sections have been associated with asthma, possibly because of modifications to the immune system (as described by the hygiene hypothesis).^[81]

Volatile organic compounds[link]

Observational studies have found that indoor exposure to volatile organic compounds (VOCs) may be one of the triggers of asthma, however experimental studies have not confirmed these observations.^[82] Even VOC exposure at low levels has been associated with an increase in the risk of pediatric asthma. Because there are so many VOCs in the air, measuring total VOC concentrations in the indoor environment may not represent the exposure of individual compounds.^[83][84] Exposure to VOCs is associated with an increase in the IL-4 producing Th2 cells and a reduction in IFN-γ producing Th1 cells. Thus the mechanism of action of VOC exposure may be allergic sensitization mediated by a Th2 cell phenotype.^[85] Different individual variations in discomfort, from no response to excessive response, were seen in one of the studies. These variations may be due to the development of tolerance during exposure.^[86] Another study has concluded that formaldehyde may cause asthma-like symptoms. Low VOC emitting materials should be used while doing repairs or renovations which decreases the symptoms related to asthma caused by VOCs and formaldehyde.^[87] In another study "the indoor concentration of aliphatic compounds (C8-C11), butanols, and 2,2,4-trimethyl 1,3-pentanediol diisobutyrate (TXIB) was significantly elevated in newly painted dwellings. The total indoor VOC was about 100 micrograms/m3 higher in dwellings painted in the last year". The author concluded that some VOCs may cause inflammatory reactions in the airways and may be the reason for asthmatic symptoms.^[88][89]

Phthalates[link]

There is a significant association between asthma-like symptoms (wheezing) among preschool children and the concentration of DEHP (phthalates) in indoor environment.^[90] DEHP (di-ethylhexyl phthalate) is a plasticizer that is commonly used in building material. The hydrolysis product of DEHP (di-ethylhexyl phthalate) is MEHP (Mono-ethylhexyl phthalate) which mimics the prostaglandins and thromboxanes in the airway leading to symptoms related to asthma.^[91] Another mechanism that has been studied regarding phthalates causation of asthma is that high phthalates level can "modulate the murine immune response to a coallergen". Asthma can develop in the adults who come in contact with heated PVC fumes.^[92] Two main type of phthalates, namely n-butyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP), have been associated between the concentration of polyvinyl chloride (PVC) used as flooring and the dust concentrations. Water leakage were associated more with BBzP, and buildings construction were associated with high concentrations of DEHP.^[93] Asthma has been shown to have a relationship with plaster wall materials and wall-to wall carpeting. The onset of asthma was also related to the floor–leveling plaster at home. Therefore, it is important to understand the health aspect of these materials in the indoor surfaces.^[94]

Genetic[link]

Over 100 genes have been associated with asthma in at least one genetic association study.^[95] However, such studies must be repeated to ensure the findings are not due to chance. Through the end of 2005, 25 genes had been associated with asthma in six or more separate populations:^[95]

Many of these genes are related to the immune system or to modulating inflammation. However, even among this list of highly replicated genes associated with asthma, the results have not been consistent among all of the populations that have been tested.^[95] This indicates that these genes are not associated with asthma under every condition, and that researchers need to do further investigation to figure out the complex interactions that cause asthma. One theory is that asthma is a collection of several diseases, and that genes might have a role in only subsets of asthma.^{[citation needed]} For example, one group of genetic differences (single nucleotide polymorphisms in 17q21) was associated with asthma that develops in childhood.^[96]

Gene–environment interactions[link]

Research suggests that some genetic variants may only cause asthma when they are combined with specific environmental exposures, and otherwise may not be risk factors for asthma.^[5]

The genetic trait, CD14 single nucleotide polymorphism (SNP) C-159T and exposure to endotoxin (a bacterial product) are a well-replicated example of a gene-environment interaction that is associated with asthma. Endotoxin exposure varies from person to person and can come from several environmental sources, including environmental tobacco smoke, dogs, and farms. Researchers have found that risk for asthma changes based on a person's genotype at CD14 C-159T and level of endotoxin exposure.^[97]

Exacerbation[link]

Some individuals will have stable asthma for weeks or months and then suddenly develop an episode of acute asthma. Different asthmatic individuals react differently to various factors.^[98] However, most individuals can develop severe exacerbation of asthma from several triggering agents.^[98][99]

Home factors that can lead to exacerbation include dust, house mites, animal dander (especially cat and dog hair), cockroach allergens and molds at any given home.^[98] Perfumes are a common cause of acute attacks in females and children. Both virus and bacterial infections of the upper respiratory tract infection can worsen asthma.^[98]

Socioeconomic factors[link]

There is good research evidence of links between the prevalence of some forms of asthma and the degree of affluence in the society concerned. This could possibly be due to the 'hygiene factor', whereby lack of childhood exposure to some environmental irritants increases the sensitivity of susceptible people to develop asthma on later exposure.^[100] Asthma deaths however are most common in low and middle income countries,.^[101]

The United States Environmental Protection Agency states that droppings and body parts from cockroaches and other insects can trigger asthma: "Cockroaches are commonly found in crowded cities and the southern regions of the United States. Cockroach allergens likely play a significant role in asthma in many urban areas."^[102]

Most likely due to income and geography, the incidence of and treatment quality for asthma varies among different racial groups.^[103] The prevalence of "severe persistent" asthma is also greater in low-income communities than those with better access to treatment.^[103][104]

Diagnosis[link]

Obstruction of the lumen of the bronchiole by mucoid exudate, goblet cell metaplasia, epithelial basement membrane thickening and severe inflammation of bronchiole in a patient with asthma.

There is currently not a precise physiologic, immunologic, or histologic test for diagnosing asthma. The diagnosis is usually made based on the pattern of symptoms (airways obstruction and hyperresponsiveness) and/or response to therapy (partial or complete reversibility) over time.^[10]

The British Thoracic Society determines a diagnosis of asthma using a ‘response to therapy’ approach. If the patient responds to treatment, then this is considered to be a confirmation of the diagnosis of asthma. The response measured is the reversibility of airway obstruction after treatment. Airflow in the airways is measured with a peak flow meter or spirometer, and the following diagnostic criteria are used by the British Thoracic Society:^[105]

• ≥20% difference on at least three days in a week for at least two weeks;
• ≥20% improvement of peak flow following treatment, for example:
  • 10 minutes of inhaled β-agonist (e.g., salbutamol);
  • six weeks of inhaled corticosteroid (e.g., beclometasone);
  • 14 days of 30 mg prednisolone.
• ≥20% decrease in peak flow following exposure to a trigger (e.g., exercise).

In contrast, the US National Asthma Education and Prevention Program (NAEPP) uses a ‘symptom patterns’ approach.^[106] Their guidelines for the diagnosis and management of asthma state that a diagnosis of asthma begins by assessing if any of the following list of indicators is present.^[13][106] While the indicators are not sufficient to support a diagnosis of asthma, the presence of multiple key indicators increases the probability of a diagnosis of asthma.^[106] Spirometry is needed to establish a diagnosis of asthma.^[106]

• Wheezing—high-pitched whistling sounds when breathing out—especially in children. (Lack of wheezing and a normal chest examination do not exclude asthma.)
• history of any of the following:
  • Cough, worse particularly at night
  • Recurrent wheeze
  • Recurrent difficulty in breathing
  • Recurrent chest tightness
• Symptoms occur or worsen in the presence of:
  • Exercise
  • Viral infection
  • Animals with fur or hair
  • House-dust mites (in mattresses, pillows, upholstered furniture, carpets)
  • Mold
  • Smoke (tobacco, wood)
  • Pollen
  • Changes in weather
  • Strong emotional expression (laughing or crying hard)
  • Airborne chemicals or dusts
  • Menstrual cycles
• Symptoms occur or worsen at night, awakening the patient

The latest guidelines from the U.S. National Asthma Education and Prevention Program (NAEPP) recommend spirometry at the time of initial diagnosis, after treatment is initiated and symptoms are stabilized, whenever control of symptoms deteriorates, and every 1 or 2 years on a regular basis.^[107] The NAEPP guidelines do not recommend testing peak expiratory flow as a regular screening method because it is more variable than spirometry. However, testing peak flow at rest (or baseline) and after exercise can be helpful, especially in young patients who may experience only exercise-induced asthma. It may also be useful for daily self-monitoring and for checking the effects of new medications.^[107] Peak flow readings can be charted together with a record of symptoms or use peak flow charting software. This allows patients to track their peak flow readings and pass information back to their doctor or respiratory therapist.^[108]

Differential diagnosis[link]

Differential diagnoses include:^[106]

• Infants and Children
  • Upper airway diseases
    • Allergic rhinitis and allergic sinusitis
  • Obstructions involving large airways
    • Foreign body in trachea or bronchus
    • Vocal cord dysfunction
    • Vascular rings or laryngeal webs
    • Laryngotracheomalacia, tracheal stenosis, or bronchostenosis
    • Enlarged lymph nodes or tumor
  • Obstructions involving small airways
    • Viral bronchiolitis or obliterative bronchiolitis
    • Cystic fibrosis
    • Bronchopulmonary dysplasia
    • Heart disease
  • Other causes
    • Recurrent cough not due to asthma
    • Aspiration from swallowing mechanism dysfunction or gastroesophageal reflux
    • Medication induced
• Adults
  • COPD (e.g., chronic bronchitis or emphysema)
  • Congestive heart failure
  • Pulmonary embolism
  • Mechanical obstruction of the airways (benign and malignant tumors)
  • Pulmonary infiltration with eosinophilia
  • Cough secondary to drugs (e.g., angiotensin-converting enzyme (ACE) inhibitors)
  • Vocal cord dysfunction

Before diagnosing asthma, alternative possibilities should be considered such as the use of known bronchoconstrictors (substances that cause narrowing of the airways, e.g. certain anti-inflammatory agents or beta-blockers). Among elderly people, the presenting symptom may be fatigue, cough, or difficulty breathing, all of which may be erroneously attributed to Chronic obstructive pulmonary disease(COPD), congestive heart failure, or simple aging.^[109]

[edit] Chronic obstructive pulmonary disease

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.^[110] It closely resembles asthma in symptoms, is correlated with more exposure to cigarette smoke, an older age, less symptom reversibility after bronchodilator administration (as measured by spirometry), and decreased likelihood of family history of atopy.^[111][112]

Others[link]

The term "atopy" was coined to describe this triad of atopic eczema, allergic rhinitis and asthma.^[56]

Pulmonary aspiration, whether direct due to dysphagia (swallowing disorder) or indirect (due to acid reflux), can show similar symptoms to asthma. However, with aspiration, fevers might also indicate aspiration pneumonia. Direct aspiration (dysphagia) can be diagnosed by performing a modified barium swallow test. If the aspiration is indirect (from acid reflux), then treatment is directed at this is indicated.^{[citation needed]}

Prevention[link]

The evidence for the effectiveness of measures to prevent the development of asthma is weak.^[113] Ones which show some promise include limiting smoke exposure both in utero and after delivery, breastfeeding, increased exposure to respiratory infection per the hygiene hypothesis (such as in those who attend daycare or are from large families).^[113]

Management[link]

A specific, customized plan for proactively monitoring and managing symptoms should be created. This plan should include the reduction of exposure to allergens, testing to assess the severity of symptoms, and the usage of medications. The treatment plan should be written down and adjusted according to changes in symptoms.^[114]

The most effective treatment for asthma is identifying triggers, such as cigarette smoke, pets, or aspirin, and eliminating exposure to them. If trigger avoidance is insufficient, the use of medication is recommended. Pharmaceutical drugs are selected based on, among other things, the severity of illness and the frequency of symptoms. Specific medications for asthma are broadly classified into fast-acting and long-acting categories.^[115][116]

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 glucocorticoids or alternatively, an oral leukotriene antagonist or a mast cell stabilizer is recommended. For those who suffer daily attacks, a higher dose of inhaled glucocorticoid is used. In a severe asthma exacerbation, oral glucocorticoids are added to these treatments.^[106]

Lifestyle modification[link]

Avoidance of triggers is a key component of improving control and preventing attacks. The most common triggers include allergens, smoke (tobacco and other), air pollution, non selective beta-blockers, and sulfite-containing foods.^{[106][117][118][119]}

Cigarette smoking and second-hand smoke (passive smoke) may reduce the effectiveness of management medications such as steroid/corticosteroid therapies.^[120]

Medications[link]

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.^[115]

Fast acting

Salbutamol metered dose inhaler commonly used to treat asthma attacks.

• Short acting beta₂-adrenoceptor agonists (SABA), such as salbutamol (albuterol USAN) are the first line treatment for asthma symptoms.^[6]
• Anticholinergic medications, such as ipratropium bromide, provide additional benefit when used in combination with SABA in those with moderate or severe symptoms.^[6] Anticholinergic bronchodilators can also be used if a person cannot tolerate a SABA.^[15]
• Older, less selective adrenergic agonists, such as inhaled epinephrine, have similar efficacy to SABAs.^[121] They are however not recommended due to concerns regarding excessive cardiac stimulation.^[122]

Long term control

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

• Glucocorticoids are generally considered the most effective treatment available for long term control.^[115] Inhaled forms are usually used except in the case of severe persistent disease, in which oral steroids may be needed.^[115] It is usually recommended that inhaled formulations be used once or twice daily, depending on the severity of symptoms.^[123]

• Long acting beta-adrenoceptor agonists (LABA) have at least a 12-hour effect. The FDA has issued a public health advisory recommending that these drugs should not be used without an accompanying steroid due to an increased risk of severe symptoms, including severe exacerbation of asthma in both children and adults.^{[9][124][125][126]}
• Leukotriene antagonists (such as zafirlukast) are an alternative to inhaled glucocorticoids, but are usually not preferred. They may also be used in addition to inhaled glucocorticoids but in this role are second line to LABA.^[115]
• Mast cell stabilizers (such as cromolyn sodium) are another non-preferred alternative to glucocorticoids.^[115]

Delivery methods

Medications are typically provided as metered-dose inhalers (MDIs) in combination with an asthma spacer or as a dry powder inhaler. The spacer is a plastic cylinder that mixes the medication with air, making it easier to receive a full dose of the drug. A nebulizer may also be used. Nebulizers and spacers are equally effective in those with mild to moderate symptoms however insufficient evidence is available to determine whether or not a difference exists in those severe symptomatology.^[127]

Adverse effects

Long-term use of inhaled glucocorticoids at conventional doses carries a minor risk for adverse effects.^[128] Risks include the development of cataracts and a mild regression in stature.^[128][129]

Other[link]

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

• Oxygen is used to alleviate hypoxia if saturations fall below 92%.^[130]
• Magnesium sulfate intravenous treatment has been shown to provide a bronchodilating effect when used in addition to other treatment in severe acute asthma attacks.^[131][132]
• Heliox, a mixture of helium and oxygen, may also be considered in severe unresponsive cases.^[132]
• Intravenous salbutamol is not supported by available evidence and is thus used only in extreme cases.^[130]
• Methylxanthines (such as theophylline) were once widely used, but do not add significantly to the effects of inhaled beta-agonists.^[130]
• The dissociative anesthetic ketamine is theoretically useful if intubation and mechanical ventilation is needed in people who are approaching respiratory arrest; however, there is no evidence from clinical trials to support this.^[133]

For those with severe persistent asthma not controlled by inhaled corticosteroids and LABAs bronchial thermoplasty can lead to clinical improvements.^[134] It involves the delivery of controlled thermal energy to the airway wall during a series of bronchoscopies and result in a prolonged reduction in airway smooth muscle mass.^[134]

Complementary medicine[link]

Many people with asthma, like those who with other chronic disorders, use alternative treatments; surveys show that roughly 50% of asthma patients use some form of unconventional therapy.^[135][136] There is little data to support the effectiveness of most of these therapies. Evidence is insufficient to support the usage of Vitamin C.^[137] Acupuncture is not recommended for the treatment as there is insufficient evidence to support its use.^[138][139] Air ionisers show no evidence that they improve asthma symptoms or benefit lung function; this applied equally to positive and negative ion generators.^[140]

Dust mite control measures, including air filtration, chemicals to kill mites, vacuuming, mattress covers and others methods had no effect on asthma symptoms.^[141] However, a review of 30 studies found that "bedding encasement might be an effective asthma treatment under some conditions" (when the patient is highly allergic to dust mite and the intervention reduces the dust mite exposure level from high levels to low levels).^[142] Washing laundry/rugs in hot water was also found to improve control of allergens.^[15]

A study of "manual therapies" for asthma, including osteopathic, chiropractic, physiotherapeutic and respiratory therapeutic manoeuvres, found there is insufficient evidence to support their use in treating.^[143] The Buteyko breathing technique for controlling hyperventilation may result in a reduction in medications use however does not have any effect on lung function.^[116] Thus an expert panel felt that evidence was insufficient to support its use.^[138]

Prognosis[link]

The prognosis for asthma is generally good, especially for children with mild disease.^[144] Of asthma diagnosed during childhood, 54% of cases will no longer carry the diagnosis after a decade.^{[citation needed]} The extent of permanent lung damage in people with asthma is unclear. Airway remodeling is observed, but it is unknown whether these represent harmful or beneficial changes.^[145] Although conclusions from studies are mixed, most studies show that early treatment with glucocorticoids prevents or ameliorates decline in lung function as measured by several parameters.^[146] For those who continue to suffer from mild symptoms, corticosteroids can help most to live their lives with few disabilities. It is more likely to consider immediate medication of inhaled corticosteroids as soon as asthma attacks occur. According to studies conducted, patients with relatively mild asthma who have received inhaled corticosteroids within 12 months of their first asthma symptoms achieved good functional control of asthma after 10 years of individualized therapy as compared to patients who received this medication after 2 years (or more) from their first attacks.^{[citation needed]} Though they (delayed) also had good functional control of asthma, they were observed to exhibit slightly less optimal disease control and more signs of airway inflammation.^{[citation needed]}

Asthma mortality has decreased over the last few decades due to better recognition and improvement in care.^[147]

Epidemiology[link]

Disability-adjusted life year for asthma per 100,000 inhabitants in 2004.^[148]

no data   <100   100–150   150–200   200–250   250–300   300–350

350–400   400–450   450–500   500–550   550–600   >600

As of 2009, 300 million people worldwide were affected by asthma leading to approximately 250,000 deaths per year.^{[12][9][149][150]}

It is estimated that asthma has a 7-10% prevalence worldwide.^[151] As of 1998, there was a great disparity in the prevalence of asthma across the world, with a trend toward more developed and westernized countries having higher rates of asthma,^[152] with as high as a 20 to 60-fold difference. Westernization however does not explain the entire difference in asthma prevalence between countries, and the disparities may also be affected by differences in genetic, social and environmental risk factors.^[61] Mortality however is most common in low to middle income countries,^[153] while symptoms were most prevalent (as much as 20%) in the United Kingdom, Australia, New Zealand, and Republic of Ireland; they were lowest (as low as 2–3%) in Eastern Europe, Indonesia, Greece, Uzbekistan, India, and Ethiopia.^[152]

Asthma affects approximately 7% of the population of the United States^[9] and 5% of people in the United Kingdom.^[154] Asthma causes 4,210 deaths per year in the United States.^[151][155] In 2005 in the United States asthma affected more than 22 million people including 6 million children.^[147] It accounted for nearly 1/2 million hospitalizations that same year.^[147] More boys have asthma than girls, but more women have it than men.^[156] In England, an estimated 261,400 people were newly diagnosed with asthma in 2005; 5.7 million people had an asthma diagnosis and were prescribed 32.6 million asthma-related prescriptions.^[157]

Increasing frequency[link]

The prevalence of childhood asthma in the United States has increased since 1980, especially in younger children.

Rates of asthma have increased significantly between the 1960s and 2008.^[158][159] Some 9% of US children had asthma in 2001, compared with just 3.6% in 1980. The World Health Organization (WHO) reports that some 10% of the Swiss population suffers from asthma today,^[160] compared with just 2% some 25–30 years ago. In the United States specifically data from several national surveys in the United States reveal the age-adjusted prevalence of asthma increased from 7.3 to 8.2 percent during the years 2001 through 2009 .^[161] Previous analysis of data from 2001 to 2007 had suggested the prevalence of asthma was stable.^[161]

Variability[link]

Asthma prevalence in the US is higher than in most other countries in the world, but varies drastically between diverse US populations.^[61] In the US, asthma prevalence is highest in Puerto Ricans, African Americans, Filipinos, Irish Americans, and Native Hawaiians, and lowest in Mexicans and Koreans.^{[162][163][164]} Mortality rates follow similar trends, and response to salbutamol is lower in Puerto Ricans than in African Americans or Mexicans.^[165][166] As with worldwide asthma disparities, differences in asthma prevalence, mortality, and drug response in the US may be explained by differences in genetic, social and environmental risk factors.

Asthma prevalence also differs between populations of the same ethnicity who are born and live in different places.^[167] US-born Mexican populations, for example, have higher asthma rates than non-US born Mexican populations that are living in the US.^[168]

There is no correlation between asthma and gender in children. More adult women are diagnosed with asthma than adult men, but this does not necessarily mean that more adult women have asthma.^[169]

History[link]

Asthma was first recognized in ancient Egypt and treatment was inhalation of frankincense.^[170] Officially recognized as a specific respiratory problem separate from others was first recognized and named by Hippocrates circa 450 BC. During the 1930s–50s, asthma was considered as being one of the 'holy seven' psychosomatic illnesses. Its aetiology was considered to be psychological, with treatment often based on psychoanalysis and other 'talking cures'.^[171] As these psychoanalysts interpreted the asthmatic wheeze as the suppressed cry of the child for its mother, they considered that the treatment of depression was especially important for individuals with asthma.^[171] Among the first papers in modern medicine published on the subject are one published in 1873, which tried to explain the pathophysiology of the disease ^[172] and one in 1872, which concluded that asthma can be cured by rubbing the chest with chloroform liniment.^[173]

Some of the first references to medical treatment include one in 1880, when Dr. J. B. Berkart used IV therapy to administer doses of a drug called pilocarpin.^[174] In 1886, F.H. Bosworth theorized a connection between asthma and hay fever.^[175] Epinephrine was first referred to in the treatment of asthma in 1905,^[176] and again for acute asthma in 1910.^[177]

Research[link]

Doxycycline and minocycline have shown effectiveness in the treatment of asthma due to immune suppressing effects.^[178]

Notes[link]