Asthma is a commonlong-terminflammatory disease of the airways. It is characterized by variable and recurring symptoms and reduced lung function. Symptoms include episodes ofwheezing,coughing, chest tightness, andshortness of breath. A sudden worsening of asthma symptoms sometimes called an 'asthma attack' or an 'asthma exacerbation' can occur whenallergens,pollen, dust, or other particles, are inhaled into the lungs, causing the bronchioles to constrict and produce mucus, which then restrictsoxygen flow to thealveoli. These may occur a few times a day or a few times per week.[2] Depending on the person, asthma symptoms may become worse at night or with exercise.[2]
Asthma is thought to be caused by a combination ofgenetic andenvironmental factors.[1] Environmental factors include exposure toair pollution andallergens.[2] Other potential triggers include medications such asaspirin andbeta blockers.[2] Diagnosis is usually based on the pattern of symptoms, response to therapy over time, andspirometry lung function testing.[3] 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.[2] Symptoms can be prevented by avoiding triggers, such asallergens and respiratoryirritants, and suppressed with the use of inhaledcorticosteroids.[6]: 169–172 [7]: 57, 72–73 Long-acting beta agonists (LABA) orantileukotriene agents may be used in addition to inhaled corticosteroids if asthma symptoms remain uncontrolled.[7]: 77–78, 90 [8] Treatment of rapidly worsening symptoms is usually with an inhaled short-actingbeta2 agonist such assalbutamol and corticosteroids taken by mouth.[6]: 214 In very severe cases, intravenous corticosteroids,magnesium sulfate, and hospitalization may be required.[6]: 373–375
In 2019, asthma affected approximately 262million people and caused approximately 461,000 deaths.[5] Most of the deaths occurred in thedeveloping world.[2] Asthma often begins inchildhood,[2] and the rates have increased significantly since the 1960s.[9] Asthma was recognized as early asAncient Egypt.[10] The wordasthma is from the Greekἆσθμα (âsthma), which means 'panting'.[11]
Asthma causes recurrent episodes ofwheezing,shortness of breath,chest tightness, andcoughing.[12] Symptoms are usually worse at night and in the early morning or in response to exercise or cold air.[13]: 8 Some people with asthma rarely experience symptoms, usually in response to triggers, whereas others may react frequently and readily and experience persistent symptoms.[7]: 22–24
Due to the diversity in onset, symptoms, outcomes, and response to treatment, asthma is often considered asyndrome — a collection of signs and symptoms — rather than a single condition.[16][17] Historically asthma was classified as being caused by external factors (extrinsic) such asallergens or by internal factors (intrinsic), unrelated to allergies.[17] Currently asthma is most commonly classified according to severity, control of symptoms,phenotypes andendotypes.[17][18]
Asthma andchronic obstructive pulmonary disease (COPD) cause airway restriction and have a wide range of overlapping mechanisms and symptoms. The main difference between the two disorders is that in asthma expiratory airflow fluctuates over time while in COPD airflowobstruction is chronic and can increase in severity over time.[7]: 131–133
Severity and symptom control
Asthma severity is determined on the basis of how much medication is required to control symptoms and exacerbations while asthma control is the burden of asthma on an individual such as symptoms and inflammation.[7]: 35 [18] Classification of asthma control does not depend on medication usage like severity does, however they often assess similar factors.[18]
Asthma control is assessed on the basis of how well the symptoms are being control and the risk of any future consequences of the disorder.[7]: 36 The frequency and severity of symptoms, impairment caused by symptoms, use of rescue inhalers, questionnaires, healthcare usage, and objective tests such as spirometry, FeNO, sputum eosinophils, and hyperresponsiveness studies are used to evaluate asthma control.[18]
Asthma severity is measured based on how difficult the disorder is to treat. Severity can only be measured once the disorder is under control. Those with mild asthma may only require as needed medication to treat the disease while those with severe asthma require high doses of medication to gain control over the disorder or may be unable to get their symptoms under control even with medications.[7]: 44
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.[19] 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.[16]
The two endotypes are distinguished based on the type of inflammation present, with the type-2 high endotype involving thetype 2 immune system response and type-2 low involvingtype 1 immune system response. Type-2 high is characterized by increasedeosinophils, increasedFractional 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, andAspirin-exacerbated respiratory disease. Type-2 low asthma phenotypes include asthma associated with obesity, neutrophilic asthma, asthma associated with cigarette smoke, and paucigranulocytic asthma.[19]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 — developedhypersensitivity. Irritant-induced asthma is a type-2 low phenotype while sensitizer-induced occupational asthma is a type-2 high phenotype.[16][19]Asthma-COPD overlap (ACO) currently lacks a consistent definition making it hard to categorize it into either endotype.[16]
Asthma exacerbation
Severity of an acute exacerbation[7]: 29, 161–170, 203–206
Near-fatal
HighPaCO2, or requiring mechanical ventilation, or both
Signs occurring during an asthma attack include the use of accessorymuscles of respiration (sternocleidomastoid andscalene muscles of the neck), there may be aparadoxical pulse (a pulse that is weaker during inhalation and stronger during exhalation), and over-inflation of the chest.[20] Ablue colour of the skin and nails may occur from lack of oxygen.[21]
A mild exacerbation is ≥200 L/min, or ≥50% of the predicted best.[22]
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.[22]
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.[23] Half of cases are due to infections with others caused by allergen, air pollution, or insufficient or inappropriate medication use.[23]
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 longer routinely used in contemporary clinical practice.[24]
Causes
Asthma is caused by a mixture of genetic and external factors. The disease manifests when those with agenetic susceptibility to asthma are exposed to specific environmental factors.[25] Environmental factors can also trigger asthma symptoms.[26]
Factors duringpregnancy that have been linked to the development of asthma include weight gain orobesity in the mother, stressful pregnancy, smoking while pregnant, the use of certain medications while pregnant andcaesarean section. Early childhood exposure tosecondhand smoke, high levels of stress in parents,respiratory infections, and indoormold orfungi have also been associated with asthma development.[27]
Respiratory tract infections, especially during early childhood or if they are severe and recurring can lead to decreased lung function and subsequent asthma.[26][28] Conversely, there has been research suggesting that certain infections during childhood may lessen the risk of developing asthma. This theory is known as the “hygiene hypothesis”.[26]
Prenatal or childhood exposure tocigarette smoke increases the likelihood of a child developing asthma. Children whose maternal grandmother smoked during pregnancy are also more likely to develop asthma, regardless of if their mothers developed asthma or smoked. Nicotine is believed to be the cause of these effects and nicotine is linked tochanges in DNA.[28]
Asthma is more commonly seen inurban environments than inrural environments. This is believed to be due to the higher presence of certain risk factors for asthma in urban settings such as traffic pollution, secondhand smoke,social inequality, lack of green spaces, andindustrialization as well as protective factors associated with rural environments such as less air pollution, early protective exposure to allergens and bacteria, and higher levels of physical activity.[27]
In those who are affected by allergies, exposure to allergens can trigger asthma symptoms.[28] However, some research has suggested that early exposure to allergens in childhood may help desensitize individuals from allergies. Other studies have shown that early exposure may increase risk of allergies and the development of allergies is multifactorial. Allergens also play a role in the development of adult-onset asthma.[27]
Adult-onset asthma is caused by relations between genetics, lifestyle factors such as obesity and smoking, and environmental factors such as an urban or rural environment, occupational exposures, and air pollution.[27] Unlike childhood asthma, which is more prevalent in males, in adults asthma is more prevalent in females.[26] Over 400 occupational exposure have been linked to asthma. Exposure toasthmagens, allergens and substances that are known to cause asthma; the amount and length of time that an individual was exposed to the substance; genetics; allergies; and smoking can affect the development of occupational asthma.[28]
Genetics
Asthma is highlypolygenic, with hundreds of common and rare genetic variants of small effect contributing to disease susceptibility, age of onset, and inflammatoryphenotypes.[29][30][31]Twin studies andfamily studies support a substantial heritable component, with estimates that roughly half or more of asthma susceptibility is explained by genetics[31] that is further modulated by environmental andepigenetic factors.[32] Largegenome-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.[29][30][33]
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 highlighttype 2 inflammation,epithelial barrier function, and bothinnate andadaptive immune signalling, including loci near or withinIL33,IL1RL1/IL18R1,TSLP,MHC class II, andGATA3.[29][30] The chromosome region 17q12–21 remains the most robustly replicated asthma locus, with effects strongest for childhood-onset disease.[34] Multiple genes in this region, includingORMDL3 andGSDMB, 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.[35][36][30]
Genetic correlation analyses demonstrate substantial overlap between asthma and other atopic disorders such aseczema andallergic 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.[30][33][37] 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.[35][38][39][40]
Many asthma-associated variants act withinregulatory 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.[30][35]
Exacerbations
Asthma exacerbations are commonly triggered by external factors or underusage of ICS medications, however exacerbations can be sudden and unexplained. Triggers for asthma exacerbations include viral respiratory infections, exposure to allergens,food allergies, outdoor air pollution, season changes or back to school season in the fall, lack of adherence to ICS, andepidemics of severe asthma exacerbations in a community.[7]: 160
Pathophysiology
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.
In asthma, the airways contract more than what is normal in response to both internal and external triggers. Thishyperresponsiveness alongside inflammation affects the nerves in the airways — making them more sensitive — and causes the body to produce too much mucus.[26] Contraction of airway smooth muscle, swelling (edema), thickening of the airway wall due to remodelling, increased mucus production, and mucus plugs contribute to narrowing of the airways. Airway hyperresponsiveness is excessive narrowing of the airways in response to stimuli that are normally harmless. This narrowing leads to variable airflow restriction and asthma symptoms. Airway hyperresponsiveness is somewhat reversible with treatment.[26][41][12]
... 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.[3][11] 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.[42]Spirometry is then used to confirm the diagnosis.[42] In children under the age of six, the diagnosis is more difficult as they are too young for spirometry.[7]: 181–184
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.[43][6]: 64–68 [4]: 18–22 It is the single best test for asthma. If theFEV1 measured by this technique improves more than 12% and increases by at least 200 millilitres following administration of abronchodilator such assalbutamol, this is supportive of the diagnosis. It however may be normal in those with a history of mild asthma, not currently acting up.[11] Ascaffeine is a bronchodilator in people with asthma, the use of caffeine before a lung function test may interfere with the results.[44]Single-breath diffusing capacity can help differentiate asthma fromCOPD.[11] It is reasonable to perform spirometry every one or two years to follow how well a person's asthma is controlled.[45]
Others
Themethacholine 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.[11]
A ≥20% difference inpeak 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.[47]
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.[51] 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.[52][53]
Prevention
Currently, the only methods of preventing asthma that have been endorsed byclinical guidelines are avoiding the use ofbroad-spectrum antibiotics in the first year of a child life, eliminating exposure to tobacco smoke bothin utero and following birth, appropriate assessment and treatment ofvitamin D deficiency during pregnancy, and vaginal birthing when possible.[7]: 213 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.[7]: 209–211
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.[7]: 50 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.[54][55] Asthma control should be reviewed during doctors appointments so that treatment can be adjusted accordingly.[13]: 63 [7]: 52–53
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.[55][54] Education includes information about avoiding triggers, self monitoring of symptoms orpeak expiratory flow, an asthma action plan, asthma control and treatment options.[13]: 28–30 [7]: 114 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.[54][7]: 115 School based education programs on how to manage asthma decrease hospitalizations for asthma in school-aged children.[7]: 116
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.[12] Exposure tocigarette 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.[54][7]: 59–60 For those with occupational asthma, it is recommended that sensitizers and allergens at work be avoided.[7]: 60–61 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.[54][7]: 61–64 Certain medications such asAspirin,beta-blockers, andnonsteroidal 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.[7]: 61
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.[7]: 60, 63
There is not enough evidence that dietary changes, including restrictive diets or supplements are helpful in managing asthma.[56] Alternative treatments such asacupuncture,air ionizers, manual therapies (osteopathic,chiropractic,physiotherapeutic andrespiratory therapeutic manoeuvres), andbreathing exercises are not recommended by clinical guidelines due to a lack of evidence that they are effective.[57] Breathing exercises do not decrease asthma exacerbations or improve lung functioning, however they can be used alongside medications to help control symptoms.[7]: 63–64
Medications for asthma are generally divided into three categories, controllers — taken daily to control symptoms, reduce exacerbations and decreaseinflammation — relievers — taken as needed for severe symptoms or exacerbations — and additional medications added on to manage more severe asthma.[55][7]: 69 Medications are prescribed at the lowest dose possible while still treating symptoms and preventing exacerbations.[54]
Devices for inhaled medications includepressurized metered dose inhaler (pMDI),dry-powder inhalers (DPI), mist inhalers andnebulizers. The choice of delivery method depends on the type of medication used, local availability, age, and ability to use the inhaler properly.[7]: 109–111 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.[54][55]
The choice of medication used for asthma management depends on symptom control, risk factors, availability, adherence, ability to use the medication, cost and environmental impact.[7]: 72 It typically takes one or two weeks for symptoms to improve after startinginhaled corticosteroids (ICS) and the response to medication is monitored whenever it is adjusted.[54][7]: 73 If asthma symptoms and exacerbations remain well controlled after two or three months, the dosage of medication can be gradually reduced to achieve symptom control at the lowest possible dose of medication.[7]: 73 If asthma symptoms and exacerbations persist despite two to three months of treatment with ICS factors such as inhaler technique, adherence, exposure to triggers,comorbidities, and alternative diagnoses are assessed before medication dosage is increased.[54][7]: 73
The first line treatment of asthma for children are ICS, for teenagers and adults guidelines recommend a combined ICS andlong-acting beta2 agonist (LABA) inhaler.[55] After a diagnosis of asthma is confirmed, ICS are started as soon as possible. Guidelines also recommend that everyone diagnosed with asthma have access to a reliever inhaler in case of symptom flare ups.[7]: 72 [54] In children younger than five, higher doses of ICS are used to treat persistent symptoms while older individuals may be treated with an additional medication. Medical guidelines recommend referring people who have persistent symptoms despite adequate treatment to an asthma specialist (usually arespirologist orallergist).[55]
Historically, asthma was treated withshort-acting β2 agonists (SABA) as needed and ICS were only used if symptoms persisted. Due to research suggesting that management with SABA over ICS was insufficient to prevent exacerbations, guidelines now prefer ICS over SABA.[12][13]: 20
For those over the age of twelve, if asthma isn’t well controlled with an ICS/formoterol inhaler then guidelines recommend that medications be taken daily instead of on an as needed basis and gradually increased until symptoms are controlled.[13]: 18–19 If higher doses of ICS/formoterol aren’t enough to control symptoms then there are several different medications that may be added in to help manage asthma. These include theleukotriene receptor antagonists (LTRA)montelukast, a mist inhaler containing the LAMAtiotropium, andazithromycin.[13]: 19 [7]: 92 [55] In those with sensitization toaeroallergens,allergen-specific immunotherapy can increase tolerance to allergens by slowly introducing the allergen to an effected person. This is done through two different methods; subcutaneous immunotherapy — injections — and sublingual immunotherapy — under the tongue.[55][7]: 104–105 Biologics can be used to reduce inflammation that may play a role in asthma symptoms.[55] Finally, oralcorticosteroids orbronchial thermoplasty may be used as last resorts for severe asthma.[7]: 93, 106–107
In children under the age of five who have comorbidatopic disorders and intermittent asthma symptoms or severe flare-ups a 8-12 week trial of low dose ICS as maintenance treatment and a SABA for flare-ups is recommended byNICE guidelines. If symptoms clear up during the trial then medication can be stopped and symptoms are monitored in the following months to watch for returning symptoms or exacerbation, in which case ICS and SABA can be started again. Persistent symptoms are treated with increasing doses of ICS and an LTRA.[13]: 24–25
Salbutamol metered dose inhaler commonly used to treat asthma attacks
Low doses of ICS for maintenance and SABA as needed are used to manage asthma in children ages six to eleven, with ICS used whenever SABA are needed to treat flare-ups. If symptoms persist then the dose of ICS may be gradually increased, a LTRA can be added on top of inhalers or a low-dose ICS-LABA or ICS-formoterol can be used instead of ICS.[13]: 22–23 [7]: 97–98
Treatment of asthma exacerbations involves several doses ofbronchodilators, oralcorticosteroids, andoxygen supplementation.Salbutamol (albuterol) is commonly used for treating exacerbations with several doses being administered every couple of hours until symptoms lessen. When exacerbations are severe or don’t subside with inhaled medications, oral corticosteroids are used and continued for a week after the exacerbation. Oxygen therapy is also used to maintain a healthyoxygen saturation.[7]: 169–170 Ipratropium, a short-actinganticholinergic, can also be used alongside other treatments to manage exacerbations in those experiencing moderate or severe symptoms. Both intravenousmagnesium sulfate andhelium–oxygen therapy are not recommended by clinical guidelines for the management of exacerbations, however they may be used in those whose symptoms do not react to other first-line treatment options.[7]: 175–176, 207
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.[58] Reasons for lowadherence range from a conscious decision to not follow the suggested medical treatment regime for various reasons including avoiding potentialside effects,misinformation, or other beliefs about the medication.[58] 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.[58]
Prognosis
The prognosis for asthma is generally good, especially for children with mild disease.[59] Mortality has decreased over the last few decades due to better recognition and improvement in care.[60] In 2010 the death rate was 170 per million for males and 90 per million for females.[61] Rates vary between countries by 100-fold.[61]
Globally, it causes moderate or severe disability in 19.4 million people as of 2004[update] (16 million of which are in low and middle-income countries).[62] Of asthma diagnosed during childhood, half of the cases will no longer carry the diagnosis after a decade.[63] Airway remodelling is observed, but it is unknown whether these represent harmful or beneficial changes.[64] 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.[65] Early treatment with corticosteroids seems to prevent or ameliorate a decline in lung function.[66] Asthma in children also has negative effects on the quality of life of their parents.[67]
In 2019, approximately 262 million people worldwide were affected by asthma, and approximately 461,000 people died from the disease.[5] Rates vary between countries, with prevalences between 1 and 29%.[7]: 24 It is more common indeveloped thandeveloping countries.[7]: 24 One thus sees lower rates in Asia, Eastern Europe, and Africa.[11] 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.[7]: 24 The reasons for these differences are unclear.[7]: 24 Low- and middle-income countries make up more than 80% of the mortality.[69]
While asthma is twice as common in boys as girls,[7]: 24 severe asthma occurs at equal rates.[70] In contrast adult women have a higher rate of asthma than men[7]: 24 and it is more common in the young than the old.[11] 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.[71][72]
Global rates of asthma have increased significantly between the 1960s and 2008[9][73] with it being recognized as a major public health problem since the 1970s.[11] Rates of asthma have plateaued in the developed world since the mid-1990s, with recent increases primarily in the developing world.[74] Asthma affects approximately 7% of the population of the United States[75] and 5% of people in the United Kingdom.[76] Canada, Australia, and New Zealand have rates of about 14–15%.[77]
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.[78] Children are more likely see a physician due to asthma symptoms after school starts in September.[79]
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).[80][81][82] 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.[83]
Health disparities
As of 2005[update], 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.[84]
In the United States, the burden of asthma falls disproportionately on racial and ethnic minorities and economically underprivileged populations.[85] As of 2016[update], 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.[86] As of 2021[update], the mortality rate for black Americans with asthma was two times higher than for white Americans.[85]
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.[85]
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.[87] 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.[87] 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.[87]
The Chinese Gold-dust Book of Cold Damage, dated the "1st year of the Zhengyuan reign period of theYuan dynasty" (1341)
Asthma was recognized inancient Egypt and was treated by drinking anincense mixture known askyphi.[10] It was officially named as a specific respiratory problem byHippocratesc. 450 BC, with the Greek word for "panting" forming the basis of our modern name.[11] In 200 BC, it was believed to be at least partly related to the emotions.[88] In the 12th century, the Jewish physician and philosopherMaimonides wroteMaqāla fī al-Rabw ("Treatise on Asthma") in Arabic.[89] 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.[90][89]Traditional Chinese medicine also offered medication for asthma, as indicated by a surviving 14th-century manuscript curated by the Wellcome Foundation.[91]
19th century
A well-documented case in the 19th century was that ofyoung 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.[92]
In 1873, one of the first papers in modern medicine on the subject tried to explain thepathophysiology of the disease while another in 1872, concluded that asthma can be cured by rubbing the chest withchloroform liniment.[93][94]Medical treatment in 1880 included the use ofintravenous doses of a drug calledpilocarpine.[95] In 1886, F. H. Bosworth theorized a connection between asthma andhay fever.[96]
20th century
1907 advertisement for Grimault's Indian Cigarettes, promoted as a means of relieving asthma. They containedbelladonna andcannabis.
At the beginning of the 20th century, treatment was focused on avoidance of allergens and the use of selective beta2-adrenergic agonists as treatment strategies.[97][98]
Epinephrine (adrenaline) was first referred to as a treatment of asthma in 1905.[99] The asthma was relived with this treatment by what was described as "vasomotorataxia of the relaxing variety". The successful results of using epinephrine provided encouraging medical data on the hypothesis that asthma was due tovasodilation and the subsequent inflammation of the swelling of the bronchial mucosa.[100]
In the 1930s, U.S. physicianAlvin Barach created, by means of spirometry, the quantification ofexpiratory flow rates tonebulized epinephrine for those with asthma, which was the first published medical report on the effectiveness of bronchodilation.[101][102]
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 othertalking cures.[103] 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.[103]
In the 1940s, the first pure β-agonist to be synthesized wasisoprenaline. Both isoprenaline and adrenaline arecatecholamines. However, isoprenaline was an effective bronchodilator that was more selective than epinephrine.[104] The efficacy of anecdotal applications oforal corticosteroids (OCS) for the asthma was published in 1952.[105] In 1958, the association between a treatment strategy of OCS and a reduction ineosinophils in thesputum was published.[106]
The use of apressurized metered dose inhaler was developed in the mid-1950s for the administration of adrenaline as well asisoproterenol, and was later used as a beta2-adrenergic agonist. Inhaled corticosteroids and selective short-acting beta agonists came into wide use in the 1960s.[107][108] In 1967,adrenergic receptors were classified into the two subtypes of theβ1 and theβ2 adrenergic receptors.[109] The β2 adrenergic receptors were found to be dominant in the lungs as well as present in thealveolar airspace.[110][111] The discovery of the β2 adrenergic receptors allowed for thediscovery and development of beta2 agonists. Specifically, it allowed for the development of selective β2-agonists starting in the 1960s.[112]
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.[113]
Notes
^abDrazen GM, Bel EH (2020)."81. Asthma". In Goldman L, Schafer AI (eds.).Goldman-Cecil Medicine. Vol. 1 (26th ed.). Philadelphia: Elsevier. pp. 527–535.ISBN978-0-323-55087-1.
^Scott JP, Peters-Golden M (September 2013). "Antileukotriene agents for the treatment of lung disease".American Journal of Respiratory and Critical Care Medicine.188 (5):538–44.doi:10.1164/rccm.201301-0023PP.PMID23822826.
^abManniche L (1999).Sacred luxuries: fragrance, aromatherapy, and cosmetics in ancient Egypt. Cornell University Press. pp. 49.ISBN978-0-8014-3720-5.
^abcdefghiMurray JF (2010). "Ch. 38 Asthma". In Mason RJ, Murray JF, Broaddus VC, Nadel JA, Martin TR, King Jr TE, Schraufnagel DE (eds.).Murray and Nadel's textbook of respiratory medicine (5th ed.). Elsevier.ISBN978-1-4160-4710-0.
^Sergel MJ, Cydulka RK (September 2009)."Ch. 75: Asthma". In Wolfson AB, Harwood-Nuss A (eds.).Harwood-Nuss' Clinical Practice of Emergency Medicine (5th ed.). Lippincott Williams & Wilkins. pp. 432–.ISBN978-0-7817-8943-1.
^Silva N, Carona C, Crespo C, Canavarro MC (June 2015). "Quality of life in pediatric asthma patients and their parents: a meta-analysis on 20 years of research".Expert Review of Pharmacoeconomics & Outcomes Research.15 (3):499–519.doi:10.1586/14737167.2015.1008459.hdl:10316/45410.PMID25651982.S2CID8768325.
^Bush A, Menzies-Gow A (December 2009). "Phenotypic differences between pediatric and adult asthma".Proceedings of the American Thoracic Society.6 (8):712–719.doi:10.1513/pats.200906-046DP.PMID20008882.
^Silva GE, Sherrill DL, Guerra S, Barbee RA (July 2004). "Asthma as a risk factor for COPD in a longitudinal study".Chest.126 (1):59–65.doi:10.1378/chest.126.1.59.PMID15249443.
^Mahdavinia M (2020). Mahdavinia M (ed.).Health Disparities in Allergic Diseases: An Evidence-Based Look at Causes, Conditions, and Outcomes. Springer Cham. pp. 145–179.doi:10.1007/978-3-030-31222-0.ISBN978-3-030-31221-3.
^"Past, present and future—b2-adrenoceptor agonists in asthma management".Respiratory Medicine.
^McCombs RP (July 1952). "Serial courses of corticotrophin or cortisone in chronic bronchial asthma".The New England Journal of Medicine.247 (1):1–6.doi:10.1056/nejm195207032470101.PMID14941270.
^Ramsahai JM, Wark PA (July 2018). "Appropriate use of oral corticosteroids for severe asthma".The Medical Journal of Australia.209 (S2):S18–S21.doi:10.5694/mja18.00134.PMID30453868.
^Lands AM, Arnold A, McAuliff JP, Luduena FP, Brown TG (May 1967). "Differentiation of receptor systems activated by sympathomimetic amines".Nature.214 (5088):597–598.Bibcode:1967Natur.214..597L.doi:10.1038/214597a0.PMID6036174.
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