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106-510: Aspirin-exacerbated respiratory disease ( AERD ), also called NSAID-exacerbated respiratory disease ( N-ERD ) or historically aspirin-induced asthma and Samter's Triad , is a long-term disease defined by three simultaneous symptoms: asthma , chronic rhinosinusitis with nasal polyps , and intolerance of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). Compared to aspirin tolerant patients, AERD patients' asthma and nasal polyps are generally more severe. Reduction or loss of

212-487: A clinically significant decrease in both subjective and objective scoring of severity of disease, but made note of the challenge for patients in following what is a fairly stringent diet. Despite these findings, experts on the disease do not believe that dietary salicylates contribute to AERD symptoms. Dietary salicylates do not significantly inhibit the COX-1 enzyme, which is the cause of AERD reactions. One confounding factor in

318-406: 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. Asthma is the result of chronic inflammation of

424-456: 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, shortly after children return to school. This might reflect

530-482: A family of inflammatory mediators derived from arachidonic acid that include CysLTs implicated in AERD pathophysiology. Drugs that prevent leukotriene production, such as zileuton , and that block leukotriene receptors, such as montelukast and zafirlukast , have proven to be useful in treatment of nasal polyposis. However, there may be limited additional benefit when used in conjunction with intra-nasal corticosteroids. In

636-570: A first line treatment for AERD. They can be delivered topically to the nasal and sinus mucosa via a variety of methods, such as nasal spray, rinse, drops, stents and exhalation delivery systems . Overall effectiveness is low-to-moderate, but wide availability and low cost make this a widely used treatment option. Stent, spray and exhalation delivery systems are generally among the most beneficial depending on outcome measured, while no major differences in adverse effects have been measured between delivery methods. Avoidance of NSAID medications will not stop

742-399: A large survey, AERD patients reported that zileuton was more effective at controlling their symptoms than montelukast. Despite this, zileuton remains less prescribed than montelukast, likely due to concerns around risk of liver enzyme elevation. Often functional endoscopic sinus surgery is required to remove nasal polyps, although they typically recur, particularly if aspirin desensitization

848-412: A person's asthma is controlled. 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

954-555: A range of biologic medicines , and antileukotrienes . Each treatment has benefits and drawbacks, so no one option can be recommended for all patients. Asthma symptoms, if not controlled via biologics or other means, are managed with standard asthma treatments such as inhaled corticosteroids and long-acting beta-agonists . Despite optimal medical management, many patients continue to require oral steroid medications to alleviate asthma and chronic nasal congestion. Common corticosteroids such as fluticasone or budesonide are often used as

1060-475: A reaction than other alcoholic beverages. Desensitization to aspirin has been found to reduce reactions to alcohol. Given that aspirin is a salicylate, specifically acetyl salicylic acid, research has gone into low-salicylate diets such as the Feingold diet to see if they benefit AERD patients. For example, a prospective randomized trial with 30 patients following a low-salicylate diet for six weeks demonstrated

1166-455: A respiratory component; severe reactions can be life threatening. The symptoms of NSAID-induced reactions are hypersensitivity reactions rather than allergic reactions that trigger other allergen -induced asthma, rhinitis, or hives. AERD is not considered an autoimmune disease , but rather a chronic immune dysregulation . EAACI/WHO classifies the syndrome as one of five types of NSAID hypersensitivity . AERD affects an estimated 0.3–0.9% of

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1272-731: A second exposure for around one week, which lines up with the half life of circulating platelets. Additional downstream products of arachidonic acid such as 15-lipoxygenase (15-LO) produced 15-HETE and 15-Oxo-ETE are significantly elevated in nasal polyps from AERD patients while other products like anti-inflammatory lipoxins are reduced. It's possible that increased 15-LO activity and preferential conversion of arachidonic acid into 15-Oxo-ETE and eoxins over lipoxins contributes to inflammation in AERD. Various innate immune cells also appear to play important roles in AERD pathogenesis. Eosinophils, mast cells, basophils and type 2 innate lymphoid (ILC2) cells have all been found at increased levels in

1378-413: A significantly higher risk compared to randomly selected controls ( odds ratio 7.2, 95% confidence interval 5.2–10). Asthma phenotyping and endotyping has emerged as a novel approach to asthma classification inspired by precision medicine which separates the clinical presentations of asthma, or asthma phenotypes, from their underlying causes, or asthma endotypes. The best-supported endotypic distinction

1484-421: A subset of patients, and may be difficult to treat. Factors that affect reaction severity include NSAID dosage, underlying asthma control, leukotriene modifier usage and the state of the patient's nasal polyps. In addition to aspirin, patients also react to other NSAIDs such as ibuprofen , and to any medication that inhibits the cyclooxygenase-1 ( COX-1 ) enzyme, although paracetamol (acetaminophen) in low doses

1590-585: 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. Non-atopic asthma, also known as intrinsic or non-allergic, makes up between 10 and 33% of cases. There is negative skin test to common inhalant allergens. Often it starts later in life, and women are more commonly affected than men. Usual treatments may not work as well. The concept that "non-atopic"

1696-667: A treatment option. The majority of those with aspirin exacerbated respiratory disease experience respiratory reactions to alcohol . One study found that 83% reported such reactions. Of those who had reactions, 75% had a sinus reaction (runny nose, nasal congestion) and 51% had a lower respiratory reaction (wheezing, shortness of breath). The current theory on the cause of these reactions is that they may be related to polyphenols found in alcoholic beverages. A 2017 study found that alcohol sensitive patients reacted to catechins in red wine, but not to resveratrol. It has been suggested that steel fermented white wines and clear liquors may cause less of

1802-429: 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

1908-432: 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

2014-1016: Is a commonly reported occupational disease . Many cases, however, are not reported or recognized as such. It is estimated that 5–25% of asthma cases in adults are work-related. A few hundred different agents have been implicated, with the most common being isocyanates , grain and wood dust, colophony , soldering flux , latex , animals, and aldehydes . The employment associated with the highest risk of problems include those who spray paint , bakers and those who process food, nurses, chemical workers, those who work with animals, welders , hairdressers and timber workers. Aspirin-exacerbated respiratory disease (AERD), also known as aspirin -induced asthma, affects up to 9% of asthmatics. AERD consists of asthma, nasal polyps, sinus disease, and respiratory reactions to aspirin and other NSAID medications (such as ibuprofen and naproxen). People often also develop loss of smell and most experience respiratory reactions to alcohol. Alcohol may worsen asthmatic symptoms in up to

2120-429: Is a history of atopic disease ; with asthma occurring at a much greater rate in those who have either eczema or hay fever . 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

2226-456: Is a kind of asthma distinguishable by recurrent, severe attacks. Type 1 brittle asthma is a disease with wide peak flow variability, despite intense medication. Type 2 brittle asthma is background well-controlled asthma with sudden severe exacerbations. Exercise can trigger bronchoconstriction both in people with or without asthma. It occurs in most people with asthma and up to 20% of people without asthma. Exercise-induced bronchoconstriction

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2332-503: Is a specific single nucleotide polymorphism in the CD14 region and exposure to endotoxin (a bacterial product). Endotoxin exposure can come from several environmental sources including tobacco smoke, dogs, and farms. Risk for asthma, then, is determined by both a person's genetics and the level of endotoxin exposure. A triad of atopic eczema , allergic rhinitis and asthma is called atopy. The strongest risk factor for developing asthma

2438-499: Is a well-recognized condition, there is not one universal agreed-upon definition. It is defined by the Global Initiative for Asthma as "a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing particularly at night or in

2544-732: Is affected, the probability of the other having the disease is approximately 25%. By the end of 2005, 25 genes had been associated with asthma in six or more separate populations, including GSTM1 , IL10 , CTLA-4 , SPINK5 , LTC4S , IL4R and ADAM33 , among others. Many of these genes are related to the immune system or modulating inflammation. Even among this list of genes supported by highly replicated studies, results have not been consistent among all populations tested. In 2006 over 100 genes were associated with asthma in one genetic association study alone; more continue to be found. Some genetic variants may only cause asthma when they are combined with specific environmental exposures. An example

2650-669: Is also preferred due to the former term giving the false impression that asthma is caused by exercise. In a patient with EIB, exercise initially follows the normal patterns of bronchodilation. However, by three minutes, the constriction sets in, which peaks at around 10–15 minutes, and usually resolves itself by an hour. During an episode of this type of bronchoconstriction, the levels of inflammatory mediators, particularly leukotrienes , histamine , and interleukin , increase. TH2-type lymphocytes are activated, with an increase in T cells expressing CD25 (IL-2R), and B cells expressing CD 23, causing increased production of IgE . After exercise,

2756-594: Is associated with a greater risk of asthma-like symptoms. Low air quality from environmental factors such as traffic pollution or high ozone levels 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

2862-500: Is associated with an increased risk of asthma in the child. 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

2968-504: 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

3074-435: 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. Family history is a risk factor for asthma, with many different genes being implicated. If one identical twin

3180-977: 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. Many environmental factors have been associated with asthma's development and exacerbation, 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, moulds. Smoking during pregnancy and after delivery

3286-473: Is classified according to the frequency of symptoms of forced expiratory volume in one second (FEV 1 ), and peak expiratory flow rate . It may also be classified as atopic or non-atopic, where atopy refers to a predisposition toward developing a type 1 hypersensitivity reaction. 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

Aspirin-exacerbated respiratory disease - Misplaced Pages Continue

3392-427: Is classified based on severity, at the moment there is no clear method for classifying different subgroups of asthma beyond this system. Finding ways to identify subgroups that respond well to different types of treatments is a current critical goal of asthma research. Recently, asthma has been classified based on whether it is associated with type 2 or non–type 2 inflammation. This approach to immunologic classification

3498-437: Is common in professional athletes. The highest rates are among cyclists (up to 45%), swimmers, and cross-country skiers. While it may occur with any weather conditions, it is more common when it is dry and cold. Inhaled beta 2 agonists do not appear to improve athletic performance among those without asthma; however, oral doses may improve endurance and strength. Asthma as a result of (or worsened by) workplace exposures

3604-464: Is commonly referred to as an asthma attack . The classic symptoms are shortness of breath , wheezing , and chest tightness . The wheezing is most often when breathing out. While these are the primary symptoms of asthma, some people present primarily with coughing , and in severe cases, air motion may be significantly impaired such that no wheezing is heard. In children, chest pain is often present. Signs occurring during an asthma attack include

3710-572: Is converted into leukotriene C 4 (LTC 4 ), which itself is converted into leukotriene D 4 (LTD 4 ) and leukotriene E 4 (LTE 4 ), both powerful bronchoconstrictors. In contrast to PGE 2 , AERD patients show significantly higher levels of prostaglandin D 2 (PGD 2 ), which exerts pro-inflammatory effects via its recruitment of eosinophils and type 2 helper T cells (T H 2) cells in addition to its direct bronchoconstrictive action. The exact mechanism by which aspirin and other COX-1 inhibitors lead to acute respiratory reactions

3816-430: 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. The evidence for the effectiveness of measures to prevent the development of asthma is weak. The World Health Organization recommends decreasing risk factors such as tobacco smoke, air pollution, chemical irritants including perfume , and

3922-432: Is currently unknown. Allergic reaction to the superantigen of Staphylococcus aureus , chronic viral infection and autoimmune mechanisms have been theorized, among others, though there is not sufficient evidence to support any specific theory. No strong genetic predisposition to or basis of AERD has been found, and familial AERD is rare. In addition, there is no relationship between past use of NSAIDs and onset of AERD AERD

4028-436: Is driven by a developing understanding of the underlying immune processes and by the development of therapeutic approaches that target type 2 inflammation. 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,

4134-411: Is due to the activation of parasympathetic nervous system . Postganglionic parasympathetic fibers will release acetylcholine causing the constriction of the smooth muscle layer surrounding the bronchi. These smooth muscle cells have muscarinic M 3 receptors on their membrane. The activation of these receptors by acetylcholine will activate an intracellular G protein , that in turn will activate

4240-531: Is generally around 3 to 5 times higher in patients with AERD that it is in those with aspirin-tolerant asthma, and increases 2 to 30 fold during an aspirin challenge test. Since nasal polyps have been identified as an important source of inflammatory compounds in AERD, much effort goes into the prevention of polyp growth and control of sinus symptoms in general. There is evidence supporting four different long-term pharmacological treatments to this end: intra-nasal corticosteroids , aspirin desensitization and therapy,

4346-534: Is generally considered safe. Selective COX-2 inhibitor NSAIDs that do not block COX-1, such as the celecoxib and rofecoxib , also are regarded as safe. Nonetheless, recent studies do find that these types of drugs, e.g. acetaminophen and celecoxib, may trigger adverse reactions in these patients; caution is recommended in using any COX inhibitors. In addition to aspirin and NSAIDs, consumption of even small amounts of alcohol also produces uncomfortable respiratory reactions in many patients. The reason for onset of AERD

Aspirin-exacerbated respiratory disease - Misplaced Pages Continue

4452-761: Is generally thought to have two major components contributing to disease pathogenesis: abnormalities in the arachidonic acid metabolic cascade and dysregulation of various innate immune cells. These two components feed into each other in a highly complex negative cycle of increasing inflammation and dysregulation that is still under active research. AERD is associated with an aberrant arachidonic acid metabolism that leads to changes in levels of two major classes of eicosanoids , specifically certain cysteinyl leukotrienes (cysLTs) and prostaglandins . Notably, reduced prostaglandin E 2 (PGE 2 ) decreases inhibition of 5-lipoxygenase (5-LO), causing increased conversion of arachidonic acid into leukotriene A 4 (LTA 4 ). LTA 4

4558-639: Is inhibited, the decreased PGE 2 production leads to mast cell degranulation and release of LTC 4 and PGD 2 , which leads to respiratory symptom exacerbation. Patients with AERD also show increased expression of leukotriene C 4 synthase (LTC 4 S), which converts LTA 4 into LTC 4 . Platelets , which express LTC 4 S and generate LTC 4 when attached to 5-LO-expressing leukocytes (including eosinophils), are also implicated in disease pathogenesis as well as acute aspirin-induced exacerbations. Additionally, after aspirin or other NSAID exposure, AERD patients generally become desensitized and tolerate

4664-399: 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. The medications listed below have demonstrated efficacy in improving asthma symptoms; however, real world use-effectiveness

4770-537: Is limited as around half of people with asthma worldwide remain sub-optimally controlled, even when treated. People with asthma may remain sub-optimally controlled either because optimum doses of asthma medications do not work (called "refractory" asthma) or because individuals are either unable (e.g. inability to afford treatment, poor inhaler technique) or unwilling (e.g., wish to avoid side effects of corticosteroids) to take optimum doses of prescribed asthma medications (called "difficult to treat" asthma). In practice, it

4876-404: Is no cure, treatment of AERD revolves around managing the symptoms of the disease. Corticosteroids , surgery, diet modifications and monoclonal antibody -based drugs are all commonly used, among other treatment options. Paradoxically, daily aspirin therapy after an initial desensitization can also help manage symptoms. Reactions to aspirin and other NSAIDs range in severity but almost always have

4982-516: Is no improvement in smell compared to placebo and there is no reduction in the need for oral corticosteroids or rescue surgery. Once desensitized to aspirin, most patients can safely take other NSAID medications again as long the daily maintenance dose is continued. Risk of adverse advents such as bleeding or gastrointestinal side effects is relatively high with daily aspirin therapy. Even a 81 mg daily aspirin regimen for cardiovascular benefits has been shown to increase risk of long-term bleeding, so

5088-637: Is no rationale why a low salicylate diet would be beneficial for AERD patients. The first adverse reactions to aspirin were described in 1902 in Germany, only four years after aspirin's commercial introduction. The first published report of an aspirin-induced asthma attack was in 1911. Initial reports on the linkage between asthma, aspirin, and nasal polyposis were made by Georges-Fernand Widal et al. in 1922. Further studies were conducted by Samter and Beers in reports published in 1968, which brought full clinical characterization. The recognition Samter brought to

5194-435: Is not fully understood, but it is theorized that by blocking IL-4α , dupilumab increases expression of EP2, the receptor for PGE 2 , back to normal levels, normalizing COX function and PGE 2 production. Low PGE 2 production and activity appear to play a key role in AERD, as PGE 2 prevents inflammatory mediator release from mast cells and inhibits 5-LO function, which decreases production of CysLTs. Leukotrienes are

5300-434: 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). Those with asthma, especially if it

5406-452: Is not possible to distinguish "refractory" from "difficult to treat" categories for patients who have never taken optimum doses of asthma medications. A related issue is that the asthma efficacy trials upon which the pharmacological treatment guidelines are based have systematically excluded the majority of people with asthma. For example, asthma efficacy treatment trials always exclude otherwise eligible people who smoke, and smoking diminishes

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5512-640: Is not undertaken. Approximately, 90% of patients have been shown to have recurrence of nasal polyps within five years after surgery, with 47% requiring revision surgery in the same time period. A complete endoscopic sinus surgery followed by aspirin desensitization has been shown to reduce the need for revision surgeries. Exact cause of nasal polyp formation is unknown, however, differential gene expression analysis of AERD nasal polyp epithelial cells versus AERD non polyp nasal mucosa revealed DMRT3 could be potentially involved in nasal polyp development in AERD patients. Furthermore, several genes are down-regulated, hinting at

5618-478: Is poorly controlled, are at increased risk for radiocontrast reactions. Cavities occur more often in people with asthma. This may be related to the effect of beta 2 -adrenergic agonists decreasing saliva. These medications may also increase the risk of dental erosions . 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

5724-423: Is so thick that great difficulty is encountered in expelling it resulting in near exhaustion at times) can bring on panic attacks unless the individual expects this and has effectively learned pursed lip breathing to more quickly transfer oxygen to the blood via the damaged alveoli resulting from the disease. The most common cause of emphysema is smoking and smoking cessation is mandatory if this incurable disease

5830-605: Is still under investigation. AERD patients exhibit a seemingly paradoxical response to COX-1 inhibition, as it leads to greatly increased PGD 2 and LTE 4 levels, instead of the expected decrease in PGD 2 and relative lack of change in LTE 4 . However, given that COX-1 catalyzes the formation of PGE 2 , a leading explanation is that patients have an increased dependence on PGE 2 and its corresponding receptor (EP2) to prevent inflammatory mediator release from mast cells . When COX-1

5936-412: Is sufficient to diagnose AERD in a patient that has both asthma and nasal polyps. However, diagnosis can be challenging during disease onset, as symptoms do not usually begin all at once. As symptoms appear, AERD may be misdiagnosed as simple allergic or nonallergic rhinitis or adult-onset asthma alone. It is only once the triad of symptoms are present that the diagnosis of AERD can be made. As there

6042-421: 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

6148-412: Is synonymous with "non-allergic" is called into question by epidemiological data that the prevalence of asthma is closely related to the serum IgE level standardized for age and sex (P<0.0001), indicating that asthma is almost always associated with some sort of IgE-related reaction and therefore has an allergic basis, although not all the allergic stimuli that cause asthma appear to have been included in

6254-722: Is the type 2-high/type 2-low distinction. Classification based on type 2 inflammation is useful in predicting which patients will benefit from targeted biologic therapy . 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

6360-482: 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. Spirometry is recommended to aid in diagnosis and management. It is the single best test for asthma. If the FEV 1 measured by this technique improves more than 12% and increases by at least 200 millilitres following administration of a bronchodilator such as salbutamol , this

6466-447: Is to be treated. Prevention of bronchoconstriction by this pathway is vital for people with emphysema and there are several anticholinergic medications that in combination with mucous thinning agents such as Guaifenesin cause significant improvement in breathing. More generally termed exercise-induced asthma , the preferred and more accurate term exercise-induced bronchoconstriction better reflects underlying pathophysiology . It

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6572-414: The conducting zone of the airways (most especially the bronchi and bronchioles ), which subsequently results in increased contractability of the surrounding smooth muscles . This among other factors leads to bouts of narrowing of the airway and the classic symptoms of wheezing. The narrowing is typically reversible with or without treatment. Occasionally the airways themselves change. Typical changes in

6678-478: The phospholipase C pathway, that will end in an increase of intracellular calcium concentrations and therefore contraction of the smooth muscle cell. The muscle contraction will cause the diameter of the bronchus to decrease, therefore increasing its resistance to airflow. Bronchoconstriction is common in people with respiratory problems, such as asthma, COPD, and cystic fibrosis. Medical management of transient bronchoconstriction or chronic bronchitis depends on

6784-423: 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 speciality practice treating mainly severe asthma patients. Additional information on

6890-509: The American Thoracic Society issued the first treatment guidelines for EIB. While a different cause, this has very similar symptoms, namely the immunological reaction involving release of inflammatory mediators. Inhalation of allergens in sensitized subjects develops into bronchoconstriction within 10 minutes, reaches a maximum within 30 minutes, and usually resolves itself within one to three hours. In some subjects,

6996-433: The U.S. could be attributed to these. The majority of the evidence does not support a causal role between paracetamol (acetaminophen) or antibiotic use and asthma. A 2014 systematic review found that the association between paracetamol use and asthma disappeared when respiratory infections were taken into account. Maternal psychological stress during pregnancy is a risk factor for the child to develop asthma. Asthma

7102-481: The ability to smell ( hyposmia , anosmia ) is extremely common, occurring in more than 90% of people with the disease. AERD most commonly begins in early- to mid-adulthood and has no known cure. While NSAID intolerance is a defining feature of AERD, avoidance of NSAIDs does not affect the onset, development or perennial nature of the disease. The cause of the disease is a dysregulation of the arachidonic acid metabolic pathway and of various innate immune cells , though

7208-671: The ability to smell—are reported in more than 90% of patients, as inflammation within the nose and sinuses likely reaches the olfactory receptors. Reactions to NSAIDs range in severity and expression. Onset is usually relatively rapid, with a mean time of around one hour after ingestion, though reactions as late as three hours have been reported. Respiratory reactions are essentially universal, with bronchoconstriction occurring in close to 90% of patients and nasal congestion and rhinorrhea occurring in more than 40%. Other symptoms include urticaria (hives), flushing, angioedema and hypotension . Gastrointestinal reactions have also been reported in

7314-471: 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,

7420-410: The air inhaled is more fully humidified and closer to body temperature . This specific condition, in the general population, can vary between 7 and 20 percent. This increases to around 80 percent in those with symptomatic asthma. In many cases, however, the constriction, even during or after strenuous exercise, is not clinically significant except in cases of severe to moderate emphysema. In May 2013,

7526-616: 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. An acute asthma exacerbation

7632-466: The airways include an increase in eosinophils and thickening of the lamina reticularis . Chronically the airways' smooth muscle may increase in size along with an increase in the numbers of mucous glands. Other cell types involved include T lymphocytes , macrophages , and neutrophils . There may also be involvement of other components of the immune system , including cytokines , chemokines , histamine , and leukotrienes among others. While asthma

7738-575: The battery of aeroallergens studied (the "missing antigen(s)" hypothesis). For example, an updated systematic review and meta-analysis of population-attributable risk (PAR) of Chlamydia pneumoniae biomarkers in chronic asthma found that the PAR for C. pneumoniae -specific IgE was 47%. 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

7844-431: The clinical prevalence of IA in adult-onset asthma is unavailable because clinicians are not trained to elicit this type of history routinely, and recollection in child-onset asthma is challenging. A population-based incident case-control study in a geographically defined area of Finland reported that 35.8% of new-onset asthma cases had experienced acute bronchitis or pneumonia in the year preceding asthma onset, representing

7950-478: The conditions will fade within one to three minutes. In most people with EIB, this is followed by a refractory period , of generally less than four hours, during which if exercise is repeated, the bronchoconstriction is less emphasised. This is probably caused by the release of prostaglandins . The underlying cause of this type of bronchoconstriction appear to be the large volume of cool, dry air inhaled during strenuous exercise. The condition appears to improve when

8056-502: The constriction does not return to normal, and recurs after three to four hours, which may last up to a day or more. The first is named the early asthmatic response , and the latter the late asthmatic response . Bronchoconstriction can occur as a result of anaphylaxis , even when the allergen is not inhaled. Bronchoconstriction is defined as the narrowing of the airways in the lungs (bronchi and bronchioles). Air flow in air passages can get restricted in three ways: The bronchial spasm

8162-448: The cycle of dysregulation and disease. Diagnosis of AERD can be difficult, as symptoms develop over time and can often be attributed to allergies, common asthma, and/or nonallergic rhinitis . AERD is generally diagnosed based on a patient's medical history, however an oral aspirin challenge at a specialized facility is considered the most definitive method of diagnosis. Patients are considered candidates for an AERD diagnosis if they meet

8268-1051: The de-differentiation phenomenon in AERD polyps. Given that dysregulation of the arachidonic acid cascade has been implicated in AERD pathogenesis and that production of arachidonic acid and its downstream products is influenced by the interaction and metabolism of omega-3 and omega-6 essential fatty acids, dietary interventions targeting the two essential fatty acids are under study. A diet low in omega-6 fatty acids and high in omega-3 fatty acids—the opposite of an average modern western diet—has been shown to reduce arachidonic acid precursors and increase eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are precursors for anti-inflammatory compounds that modulate leukotrienes, prostaglandins and thromboxanes that have been implicated in AERD pathogenesis. Initial studies have shown that decreasing omega-6 intake and increasing omega-3 intake decrease urinary LTE 4 and prostaglandin D 2 levels and significantly improved overall symptoms. AERD specialists routinely recommend this diet as

8374-482: 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 ἆσθμα , âsthma , which means 'panting'. Asthma is characterized by recurrent episodes of wheezing , shortness of breath , chest tightness , and coughing . Sputum may be produced from

8480-421: 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 has been linked to the development of asthma. Also, delivery via caesarean section is associated with an increased risk (estimated at 20–80%) of asthma – this increased risk

8586-489: The disease through his studies led to it being called "Samter's triad", although today "aspirin-exacerbated respiratory disease" is preferred to better reflect the progressive nature of the condition even when patients abstain from NSAIDs. EDAR ( EDAR hypohidrotic ectodermal dysplasia ) Asthma Asthma is a common long-term inflammatory disease of the airways of the lungs . Asthma occurs when allergens , pollen , dust, or other particles, are inhaled into

8692-546: 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". 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

8798-455: The effectiveness of new medications. It may also be helpful in guiding treatment in those with acute exacerbations. Asthma is clinically classified according to the frequency of symptoms, forced expiratory volume in one second (FEV 1 ), and peak expiratory flow rate . 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). While asthma

8904-428: The efficacy of inhaled corticosteroids, the mainstay of asthma control management. Bronchoconstriction The condition has a number of causes, the most common being emphysema as well as asthma . Exercise and allergies can bring on the symptoms in an otherwise asymptomatic individual. With emphysema the shortness of breath due to effective bronchoconstriction from excessive very thick mucus blockage (it

9010-705: The epithelial cells to release more cytokines and inflammatory molecules, creating a feed-forward negative cycle of increasing inflammation. Eosinophils are also activated by ILC2-released IL-5 and epithelial-cell released IL-33, causing them to release more CysLTs and PGD 2 , which in turn further active ILC2. Likewise, mast cells are also activated by epithelial-cell released IL-25, IL-33 and TSLP, leading to further CysLT and PGD 2 production. Basophils, which are degranulated in AERD nasal polyps, also appear to be important sources of IL-4 and IL-13. In addition to activating immune cells, IL-4 and IL-13 have been shown to significantly increase 15-LO activity, further playing into

9116-527: The following three points: Further, if a patient meets two or more of the following criteria, then an AERD diagnosis is strongly considered: High urinary leukotriene E 4 (uLTE 4 ) concentration is also a sign of AERD, especially when noted in conjunction with the criteria listed above due. High uLTE 4 concentration alone cannot be used to diagnose AERD, however it may be possible to rule out AERD in patients without high uLTE 4 due to its strong negative predictive value . Urinary LTE 4 concentration

9222-587: The general population in the US, including around 7% of all asthmatics, about 14% of adults with severe asthma, and ~5-10% of patients with adult onset asthma. AERD is uncommon among children, with around 6% of patients, predominantly female, reporting disease onset during childhood. It is more prevalent among women by up to a 2:1 margin, usually begins in the patient's twenties to forties, with mean age of onset around 35. AERD patients may not have any allergies, though allergies are significantly more common in AERD patients than

9328-541: The general population. While AERD has been found to affect essentially all ethnicities, it is less common in parts of Asia where nasal polyps caused by type 2 inflammation are relatively more rare. While disease progression varies, most commonly the first symptom is rhinitis (inflammation or irritation of the nasal mucosa), which may manifest as sneezing, runny nose, or congestion. The disorder typically progresses to asthma, then nasal polyposis, with aspirin sensitivity coming last. Hyposmia or anosmia —reduction or loss of

9434-671: The highest certainty and magnitude of improvement effect. However, due to the high cost and systemic nature of biologics, some patients whose symptoms are sufficiently controlled with other treatments may prefer to avoid them or not qualify under stricter prescription guidelines. Among biologics and aspirin desensitization and therapy, dupilumab (Dupixent) was show to be the most effective across six different patient-important outcomes. Dupilumab and omalizumab have been shown to increase aspirin tolerance in AERD patients, however mepolizumab does not appear to have this effect. The mechanism through which dupilumab treats AERD and restores aspirin tolerance

9540-451: The home if a person has allergic symptoms to said pet. Dietary restrictions during pregnancy or when breastfeeding have not been found to be effective at preventing asthma in children and are not recommended. Omega-3 consumption, Mediterranean diet and antioxidants have been suggested by some studies to potentially help prevent crises but the evidence is still inconclusive. Reducing or eliminating compounds known to sensitive people from

9646-460: The initial cause of this dysregulation is currently unknown. This dysregulation leads to an imbalance of immune related molecules, including an overproduction of inflammatory compounds such as leukotriene E 4 and an underproduction of anti-inflammatory mediators such as prostaglandin E 2 . This imbalance, among other factors, leads to chronic inflammation of the respiratory tract . A history of respiratory reactions to aspirin or others NSAIDs

9752-801: The lung by coughing but is often hard to bring up. During recovery from an asthma attack (exacerbation) , the sputum may appear pus-like due to high levels of white blood cells called eosinophils . Symptoms are usually worse at night and in the early morning or in response to exercise or cold air. Some people with asthma rarely experience symptoms, usually in response to triggers, whereas others may react frequently and readily and experience persistent symptoms. 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

9858-418: The lungs, causing the bronchioles to constrict and produce mucus, which then restricts oxygen flow to the alveoli . It is characterized by variable and recurring symptoms, reversible airflow obstruction , and easily triggered bronchospasms . Symptoms include episodes of wheezing , coughing , chest tightness, and shortness of breath . These may occur a few times a day or a few times per week. Depending on

9964-564: The nasal polyps of AERD patients and appear to be part of the negative cycle of inflammation in AERD. ILC2 cells are activated by CysLTs and PGD 2 in addition to a class of cytokines called alarmins that are released by epithelial cells , including IL-25 , IL-33 and thymic stromal lymphopoietin (TSLP). Strongly activated ILC2s release IL-4 , IL-5 and IL-13 . These cytokines lead to increased eosinophil recruitment, excessive mucus production via goblet cells , and promotion of T H 2 and immunoglobulin E responses. These responses cause

10070-422: The number of lower respiratory infections . Other efforts that show promise include: limiting smoke exposure in utero , breastfeeding , and increased exposure to daycare or large families, but none are well supported enough to be recommended for this indication. Early pet exposure may be useful. Results from exposure to pets at other times are inconclusive and it is only recommended that pets be removed from

10176-460: 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

10282-525: The predicted best. 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. 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

10388-481: The progression of the disease. However, one treatment option is desensitization to aspirin, undertaken at a clinic or hospital specializing in such treatment. Patients who are desensitized then take a maintenance dose of aspirin daily to maintain their desensitization. The recommended maintenance dose for symptom control is 650 mg to 1300 mg aspirin daily. While on daily aspirin, patients experience improved quality of life and reduced nasal symptoms, however, there

10494-653: 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

10600-550: The risk of developing asthma when acquired as young children. Certain other infections, however, may decrease the risk. 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

10706-502: The significantly higher aspirin doses used for maintenance therapy are of some concern. This is borne out in studies on AERD patients—compared against standard of care and biologic medicines, aspirin therapy has a significantly higher rate of adverse outcomes. Various novel biologic monoclonal antibody medications that have come to market in recent years have been used to treat AERD including dupilumab , mepolizumab , omalizumab , and benralizumab . Among treatment options, biologics have

10812-449: The study that showed a benefit from avoidance of dietary salicylates is that a low salicylate diet involves eliminating wine and beer. The majority of AERD patients react to wine and beer for reasons that do not involve their salicylate content. There is also a strong placebo effect involved with any dietary intervention. In contrast to aspirin, dietary salicylates are not acetylated and therefore do not block cyclooxygenases and hence, there

10918-424: 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

11024-413: 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. In a mild exacerbation the peak expiratory flow rate (PEFR) is ≥200 L/min, or ≥50% of

11130-572: The use of inhaled corticosteroids . Long-acting beta agonists (LABA) or antileukotriene agents may be used in addition to inhaled corticosteroids if asthma symptoms remain uncontrolled. Treatment of rapidly worsening symptoms is usually with an inhaled short-acting beta 2 agonist such as salbutamol and corticosteroids taken by mouth. In very severe cases, intravenous corticosteroids, magnesium sulfate , and hospitalization may be required. In 2019 asthma affected approximately 262 million people and caused approximately 461,000 deaths. Most of

11236-583: The workplace may be effective. It is not clear if annual influenza vaccinations affect the risk of exacerbations. Immunization, however, is recommended by the World Health Organization. Smoking bans are effective in decreasing exacerbations of asthma. While there is no cure for asthma, symptoms can typically be improved. The most effective treatment for asthma is identifying triggers, such as cigarette smoke , pets or other allergens, and eliminating exposure to them. If trigger avoidance

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