<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Asthma and can you explain it in depth? [/INST] Asthma is a long-term inflammatory disease of the airways of the lungs. 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 the person, asthma symptoms may become worse at night or with exercise.Asthma is thought to be caused by a combination of genetic and environmental factors. Environmental factors include exposure to air pollution and allergens. Other potential triggers include medications such as aspirin and beta blockers. Diagnosis is usually based on the pattern of symptoms, response to therapy over time, and spirometry lung function testing. Asthma is classified according to the frequency of symptoms, forced expiratory volume in one second (FEV1), 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 can be controlled. Symptoms can be prevented by avoiding triggers, such as allergens and respiratory irritants, and suppressed with 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 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".

Signs and symptoms
Asthma is characterized by recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing. Sputum may be produced from the lung by coughing but is often hard to bring up. During recovery from an asthma attack (exacerbation), it 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.

Associated conditions
A number of other health conditions occur more frequently in people with asthma, including gastroesophageal reflux disease (GERD), rhinosinusitis, and obstructive sleep apnea. Psychological disorders are also more common, with anxiety disorders occurring in between 16 and 52% and mood disorders in 14–41%. It is not known whether asthma causes psychological problems or psychological problems lead to asthma. Current asthma, but not former asthma, is associated with increased all-cause mortality, heart disease mortality, and chronic lower respiratory tract disease mortality. Asthma, particularly severe asthma, is strongly associated with development of chronic obstructive pulmonary disease (COPD). Those with asthma, especially if it 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 agonists decreasing saliva. These medications may also increase the risk of dental erosions.

Causes
Asthma is caused by a combination of complex and incompletely understood environmental and genetic interactions. These influence both its severity and its responsiveness to treatment. It is believed that the recent increased rates of asthma are due to changing epigenetics (heritable factors other than those related to the DNA sequence) and a changing living environment. Asthma that starts before the age of 12 years old is more likely due to genetic influence, while onset after age 12 is more likely due to environmental influence.

Environmental
Many environmental factors have been associated with asthmas development and exacerbation, including, allergens, air pollution, and other environmental chemicals. Smoking during pregnancy and after delivery 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 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.The majority of the evidence does not support a causal role between acetaminophen (paracetamol) or antibiotic use and asthma. A 2014 systematic review found that the association between acetaminophen use and asthma disappeared when respiratory infections were taken into account. Acetaminophen use by a mother during pregnancy is also associated with an increased risk of the child developing asthma. Maternal psychological stress during pregnancy is a risk factor for the child to develop asthma.Asthma is associated with exposure to indoor allergens. Common indoor allergens include dust mites, cockroaches, animal dander (fragments of fur or feathers), and mold. Efforts to decrease dust mites have been found to be ineffective on symptoms in sensitized subjects. Weak evidence suggests that efforts to decrease mold by repairing buildings may help improve asthma symptoms in adults. Certain viral respiratory infections, such as respiratory syncytial virus and rhinovirus, may increase the risk of developing asthma when acquired as young children. Certain other infections, however, may decrease the risk.

Hygiene hypothesis
The hygiene hypothesis attempts to explain the increased rates of asthma worldwide as a direct and unintended result of reduced exposure, during childhood, to non-pathogenic bacteria and viruses. It has been proposed that the reduced exposure to bacteria and viruses is due, in part, to increased cleanliness and decreased family size in modern societies. Exposure to bacterial endotoxin in early childhood may prevent the development of asthma, but exposure at an older age may provoke bronchoconstriction. Evidence supporting the hygiene hypothesis includes lower rates of asthma on farms and in households with pets.Use of antibiotics in early life 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 is attributed to the lack of healthy bacterial colonization that the newborn would have acquired from passage through the birth canal. There is a link between asthma and the degree of affluence which may be related to the hygiene hypothesis as less affluent individuals often have more exposure to bacteria and viruses.

Genetic
Family history is a risk factor for asthma, with many different genes being implicated. If one identical twin 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 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 persons genetics and the level of endotoxin exposure.

Medical conditions
A triad of atopic eczema, allergic rhinitis and asthma is called atopy. The strongest risk factor for developing asthma is a history of atopic disease; with asthma occurring at a much greater rate in those who have either eczema or hay fever. Asthma has been associated with eosinophilic granulomatosis with polyangiitis (formerly known as Churg–Strauss syndrome), an autoimmune disease and vasculitis. Individuals with certain types of urticaria may also experience symptoms of asthma.There is a correlation between obesity and the risk of asthma with both having increased in recent years. Several factors may be at play including decreased respiratory function due to a buildup of fat and the fact that adipose tissue leads to a pro-inflammatory state.Beta blocker medications such as propranolol can trigger asthma in those who are susceptible. Cardioselective beta-blockers, however, appear safe in those with mild or moderate disease. Other medications that can cause problems in asthmatics are angiotensin-converting enzyme inhibitors, aspirin, and NSAIDs. Use of acid suppressing medication (proton pump inhibitors and H2 blockers) during pregnancy is associated with an increased risk of asthma in the child.

Exacerbation
Some individuals will have stable asthma for weeks or months and then suddenly develop an episode of acute asthma. Different individuals react to various factors in different ways. Most individuals can develop severe exacerbation from a number of triggering agents.Home factors that can lead to exacerbation of asthma include dust, animal dander (especially cat and dog hair), cockroach allergens and mold. Perfumes are a common cause of acute attacks in women and children. Both viral and bacterial infections of the upper respiratory tract can worsen the disease. Psychological stress may worsen symptoms – it is thought that stress alters the immune system and thus increases the airway inflammatory response to allergens and irritants.Asthma exacerbations in school‐aged children peak in autumn, shortly after children return to school. This might reflect a combination of factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. There is limited evidence to guide possible approaches to reducing autumn exacerbations, but while costly, seasonal omalizumab treatment from four to six weeks before school return may reduce autumn asthma exacerbations.

Pathophysiology
Asthma is the result of chronic inflammation of the conducting zone of the airways (most especially the bronchi and bronchioles), which subsequently results in increased contractability of the surrounding smooth muscles. 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 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.

Diagnosis
While asthma 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 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 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
Spirometry is recommended to aid in diagnosis and management. It is the single best test for asthma. If the FEV1 measured by this technique improves more than 12% and increases by at least 200 milliliters following administration of a bronchodilator such as salbutamol, this is supportive of the diagnosis. It however may be normal in those with a history of mild asthma, not currently acting up. As caffeine is a bronchodilator in people with asthma, the use of caffeine before a lung function test may interfere with the results. Single-breath diffusing capacity can help differentiate asthma from COPD. It is reasonable to perform spirometry every one or two years to follow how well a persons asthma is controlled.

Others
The methacholine challenge involves the inhalation of increasing concentrations of a substance that causes airway narrowing in those predisposed. If negative it means that a person does not have asthma; if positive, however, it is not specific for the disease.Other supportive evidence includes: a ≥20% difference in peak expiratory flow rate on at least three days in a week for at least two weeks, a ≥20% improvement of peak flow following treatment with either salbutamol, inhaled corticosteroids or prednisone, or a ≥20% decrease in peak flow following exposure to a trigger. Testing peak expiratory flow is more variable than spirometry, however, and thus not recommended for routine diagnosis. It may be useful for daily self-monitoring in those with moderate to severe disease and for checking the effectiveness of new medications. It may also be helpful in guiding treatment in those with acute exacerbations.

Classification
Asthma is clinically classified according to the frequency of symptoms, forced expiratory volume in one second (FEV1), 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 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.Although asthma is a chronic obstructive condition, it is not considered as a part of chronic obstructive pulmonary disease, as this term refers specifically to combinations of disease that are irreversible such as bronchiectasis and emphysema. Unlike these diseases, the airway obstruction in asthma is usually reversible; however, if left untreated, the chronic inflammation from asthma can lead the lungs to become irreversibly obstructed due to airway remodeling. In contrast to emphysema, asthma affects the bronchi, not the alveoli. The combination of asthma with a component of irreversible airways obstruction has been termed the asthma-chronic obstructive disease (COPD) overlap syndrome (ACOS). Compared to other people with "pure" asthma or COPD, people with ACOS exhibit increased morbidity, mortality and possibly more comorbidities.

Asthma exacerbation
An acute asthma exacerbation 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 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 color 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 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 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-induced
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 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 beta2-agonists do not appear to improve athletic performance among those without asthma, however, oral doses may improve endurance and strength.

Occupational
Asthma as a result of (or worsened by) workplace exposures 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-induced asthma
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-induced asthma
Alcohol may worsen asthmatic symptoms in up to a third of people. This may be even more common in some ethnic groups such as the Japanese and those with aspirin-induced asthma. Other studies have found improvement in asthmatic symptoms from alcohol.

Non-atopic asthma
Non-atopic asthma, also known as intrinsic or non-allergic, makes up between 10 and 33% of cases. There is negative skin test to common inhalant allergens. Often it starts later in life, and women are more commonly affected than men. Usual treatments may not work as well. The concept that "non-atopic" is synonymous with "non-allergic" is called into question by epidemiological data that the prevalence of asthma is closely related to the serum IgE level standardized for age and sex (P<0.0001), indicating that asthma is almost always associated with some sort of IgE-related reaction and therefore has an allergic basis, although not all the allergic stimuli that cause asthma appear to have been included in the battery of aeroallergens studied (the "missing antigen(s)" hypothesis). 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
When queried, asthma patients may report that their first asthma symptoms began after an acute lower respiratory tract illness. This type of history has been labelled the "infectious asthma" (IA) syndrome, or as "asthma associated with infection" (AAWI) to distinguish infection-associated asthma initiation from the well known association of respiratory infections with asthma exacerbations. Reported prevalences of IA for adults range from around 40% in a primary care practice to 70% in a specialty practice treating mainly severe asthma patients. The true population prevalence  of IA in adult-onset asthma is unknown because clinicians are not trained to elicit this type of history routinely, and recollection in child-onset asthma is challenging.

Differential diagnosis
Many other conditions can cause symptoms similar to those of asthma. In children, symptoms may be due to other upper airway diseases such as allergic rhinitis and sinusitis, as well as other causes of airway obstruction including foreign body aspiration, tracheal stenosis, laryngotracheomalacia, vascular rings, enlarged lymph nodes or neck masses. Bronchiolitis and other viral infections may also produce wheezing. In adults, COPD, congestive heart failure, airway masses, as well as drug-induced coughing due to ACE inhibitors may cause similar symptoms. In both populations vocal cord dysfunction may present similarly.Chronic obstructive pulmonary disease can coexist with asthma and can occur as a complication of chronic asthma. After the age of 65, most people with obstructive airway disease will have asthma and COPD. In this setting, COPD can be differentiated by increased airway neutrophils, abnormally increased wall thickness, and increased smooth muscle in the bronchi. However, this level of investigation is not performed due to COPD and asthma sharing similar principles of management: corticosteroids, long-acting beta-agonists, and smoking cessation. It closely resembles asthma in symptoms, is correlated with more exposure to cigarette smoke, an older age, less symptom reversibility after bronchodilator administration, and decreased likelihood of family history of atopy.

Prevention
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 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 the home if a person has allergic symptoms to said pet.Dietary restrictions during pregnancy or when breast feeding have not been found to be effective at preventing asthma in children and are not recommended. Omega-3 consumption, mediterranean diet and anti-oxidants have been suggested by some studies that might help preventing crisis but the evidence is still inconclusive.Reducing or eliminating compounds known to sensitive people from the work place may be effective. It is not clear if annual influenza vaccinations affects the risk of exacerbations. Immunization, however, is recommended by the World Health Organization. Smoking bans are effective in decreasing exacerbations of asthma.

Management
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 aspirin, and eliminating exposure to them. If trigger avoidance is insufficient, the use of medication is recommended. Pharmaceutical drugs are selected based on, among other things, the severity of illness and the frequency of symptoms. Specific medications for asthma are broadly classified into fast-acting and long-acting categories. The medications listed below have demonstrated efficacy in improving asthma symptoms, however "real world" use-effectiveness is limited as around half of people with asthma worldwide remain sub-optimally controlled, even when treated. People with asthma may remain sub-optimally controlled either because optimum doses of asthma medications do not work (called "refractory" asthma) or because individuals are either unable (e.g. inability to afford treatment, poor inhaler technique) or unwilling (e.g., wish to avoid side effects of corticosteroids) to take optimum doses of prescribed asthma medications (called "difficult to treat" asthma). In practice, it is not possible to distinguish "refractory" from "difficult to treat" categories for patients who have never taken optimum doses of asthma medications. A related issue is that the asthma efficacy trials upon which the pharmacological treatment guidelines are based have systematically excluded the majority of people with asthma. For example, asthma efficacy treatment trials always exclude otherwise eligible people who smoke, and smoking blunts the efficacy of inhaled corticosteroids, the mainstay of asthma control management.Bronchodilators are recommended for short-term relief of symptoms. In those with occasional attacks, no other medication is needed. If mild persistent disease is present (more than two attacks a week), low-dose inhaled corticosteroids or alternatively, a leukotriene antagonist or a mast cell stabilizer by mouth is recommended. For those who have daily attacks, a higher dose of inhaled corticosteroids is used. In a moderate or severe exacerbation, corticosteroids by mouth are added to these treatments.People with asthma have higher rates of anxiety, psychological stress, and depression. This is associated with poorer asthma control. Cognitive behavioral therapy may improve quality of life, asthma control, and anxiety levels in people with asthma.Improving peoples knowledge about asthma and using a written action plan has been identified as an important component of managing asthma. Providing educational sessions that include information specific to a persons culture is likely effective. More research is necessary to determine if increasing preparedness and knowledge of asthma among school staff and families using home-based and school interventions results in long term improvements in safety for children with asthma. School-based asthma self-management interventions, which attempt to improve knowledge of asthma, its triggers and the importance of regular practitioner review, may reduce hospital admissions and emergency department visits. These interventions may also reduce the number of days children experience asthma symptoms and may lead to small improvements in asthma-related quality of life. More research is necessary to determine if shared-decision-making is helpful for managing adults with asthma or if a personalized asthma action plan is effective and necessary. Some people with asthma use pulse oximeters to monitor their own blood oxygen levels during an asthma attack. However, there is no evidence regarding the use in these instances.

Lifestyle modification
Avoidance of triggers is a key component of improving control and preventing attacks. The most common triggers include allergens, smoke (from tobacco or other sources), air pollution, non selective beta-blockers, and sulfite-containing foods. Cigarette smoking and second-hand smoke (passive smoke) may reduce the effectiveness of medications such as corticosteroids. Laws that limit smoking decrease the number of people hospitalized for asthma. Dust mite control measures, including air filtration, chemicals to kill mites, vacuuming, mattress covers and others methods had no effect on asthma symptoms. There is insufficient evidence to suggest that dehumidifiers are helpful for controlling asthma.Overall, exercise is beneficial in people with stable asthma. Yoga could provide small improvements in quality of life and symptoms in people with asthma. More research is necessary to determine how effective weight loss is on improving quality of life, the usage of health care services, and adverse effects for people of all ages with asthma.

Medications
Medications used to treat asthma are divided into two general classes: quick-relief medications used to treat acute symptoms; and long-term control medications used to prevent further exacerbation. Antibiotics are generally not needed for sudden worsening of symptoms or for treating asthma at any time.

Medications of asthma exacerbations
Short-acting beta2-adrenoceptor agonists (SABA), such as salbutamol (albuterol USAN) are the first line treatment for asthma symptoms. They are recommended before exercise in those with exercise induced symptoms.
Anticholinergic medications, such as ipratropium, provide additional benefit when used in combination with SABA in those with moderate or severe symptoms and may prevent hospitalizations. Anticholinergic bronchodilators can also be used if a person cannot tolerate a SABA. If a child requires admission to hospital additional ipratropium does not appear to help over a SABA. For children over 2 years old with acute asthma symptoms, inhaled anticholinergic medications taken alone is safe but is not as effective as inhaled SABA or SABA combined with inhaled anticholinergic medication. Adults who receive combined inhaled medications that includes short-acting anticholinergics and SABA may be at risk for increased adverse effects such as experiencing a tremor, agitation, and heart beat palpitations compared to people who are treated with SABA by itself.
Older, less selective adrenergic agonists, such as inhaled epinephrine, have similar efficacy to SABAs. They are however not recommended due to concerns regarding excessive cardiac stimulation.
Corticosteroids can also help with the acute phase of an exacerbation because of their antiinflamatory properties. The benefit of systemic and oral corticosteroids is well established. Inhaled or nebulized corticosteroids can also be used. For adults and children who are in the hospital due to acute asthma, systemic (IV) corticosteroids improve symptoms. A short course of corticosteroids after an acute asthma exacerbation may help prevent relapses and reduce hospitalizations.
Other remedies, less established, are intravenous or nebulized magnesium sulfate and helium mixed with oxygen. Aminophylline could be used with caution as well.
Mechanical ventilation is the last resort in case of severe hypoxemia.
Intravenous administration of the drug aminophylline does not provide an improvement in bronchodilation when compared to standard inhaled beta-2 agonist treatment. Aminophylline treatment is associated with more adverse effects compared to inhaled beta-2 agonist treatment.

Long–term control
Corticosteroids are generally considered the most effective treatment available for long-term control. Inhaled forms are usually used except in the case of severe persistent disease, in which oral corticosteroids may be needed. Dosage depends on the severity of symptoms. High dosage and long term use might lead to the appearance of common adverse effects which are  growth delay, adrenal suppression, and osteoporosis. Continuous (daily) use of an inhaled corticosteroid, rather than its intermitted use, seems to provide better results in controlling asthma exacerbations. Commonly used corticosteroids are  budesonide, fluticasone, mometasone and ciclesonide.
Long-acting beta-adrenoceptor agonists (LABA) such as salmeterol and formoterol can improve asthma control, at least in adults, when given in combination with inhaled corticosteroids. In children this benefit is uncertain. When used without steroids they increase the risk of severe side-effects, and with corticosteroids they may slightly increase the risk. Evidence suggests that for children who have persistent asthma, a treatment regime that includes LABA added to inhaled corticosteroids may improve lung function but does not reduce the amount of serious exacerbations. Children who require LABA as part of their asthma treatment may need to go to the hospital more frequently.
Leukotriene receptor antagonists (anti-leukotriene agents such as montelukast and zafirlukast) may be used in addition to inhaled corticosteroids, typically also in conjunction with a LABA.  For adults or adolescents who have persistent asthma that is not controlled very well, the addition of anti-leukotriene agents along with daily inhaled corticosteriods improves lung function and reduces the risk of moderate and severe asthma exacerbations. Anti-leukotriene agents may be effective alone for adolescents and adults, however there is no clear research suggesting which people with asthma would benefit from anti-leukotriene receptor alone.  In those under five years of age, anti-leukotriene agents were the preferred add-on therapy after inhaled corticosteroids. A 2013 Cochrane systematic review concluded that anti-leukotriene agents appear to be of little benefit when added to inhaled steroids for treating children. A similar class of drugs, 5-LOX inhibitors, may be used as an alternative in the chronic treatment of mild to moderate asthma among older children and adults. As of 2013 there is one medication in this family known as zileuton.
Mast cell stabilizers (such as cromolyn sodium) are safe alternatives to corticosteroids but not preferred because they have to be administered frequently.
Oral Theophyllines are sometimes used for controlling chronic asthma, but their used is minimized because of their side effects.
Omalizumab, a monoclonal Antibody Against IgE, is a novel way to lessen exacerbations by lessening the levels of circulating IgE that play a significant role at allergic asthma.
Anticholinergic medications such as ipratropium bromide have not been shown to be beneficial for treating chronic asthma in children over 2 years old, but is not suggested for routine treatment of chronic asthma in adults.
There is no strong evidence to recommend chloroquine medication as a replacement for taking corticosteroids by mouth (for those who are not able to tolerate inhaled steroids). Methotrexate is not suggested as a replacement for taking corticosteriods by mouth ("steroid sparing") due to the adverse effects associated with taking methotrexate and the minimal relief provided for asthma symptoms.
Macrolide antibiotics, particularly the azalide macrolide azithromycin, are a recently added GINA-recommended treatment option for both eosinophilic and non-eosinophilic severe, refractory asthma based on azithromycins efficacy in reducing moderate and severe exacerbations combined. Azithromycins mechanism of action is not established, and could involve  pathogen- and/or host-directed anti-inflammatory activities. Limited clinical observations suggest that some patients with new-onset asthma and with "difficult-to-treat" asthma (including those with the asthma-COPD overlap syndrome - ACOS) may respond dramatically to azithromycin. However, these groups of asthma patients have not been studied in randomized treatment trials and patient selection needs to be carefully individualized.For children with asthma which is well-controlled on combination therapy of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA), the benefits and harms of stopping LABA and stepping down to ICS-only therapy are uncertain. In adults who have stable asthma while they are taking a combination of LABA and inhaled corticosteroids (ICS), stopping LABA may increase the risk of asthma exacerbations that require treatment with corticosteroids by mouth. Stopping LABA probably makes little or no important difference to asthma control or asthma-related quality of life. Whether or not stopping LABA increases the risk of serious adverse events or exacerbations requiring an emergency department visit or hospitalisation is uncertain.

Delivery methods
Medications are typically provided as metered-dose inhalers (MDIs) in combination with an asthma spacer or as a dry powder inhaler. The spacer is a plastic cylinder that mixes the medication with air, making it easier to receive a full dose of the drug. A nebulizer may also be used. Nebulizers and spacers are equally effective in those with mild to moderate symptoms. However, insufficient evidence is available to determine whether a difference exists in those with severe disease. For delivering short-acting beta-agonists in acute asthma in children, spacers may have advantages compared to nebulisers, but children with life-threatening asthma have not been studied. There is no strong evidence for the use of intravenous LABA for adults or children who have acute asthma. There is insufficient evidence to directly compare the effectiveness of a metered-dose inhaler attached to a homemade spacer compared to commercially available spacer for treating children with asthma.

Adverse effects
Long-term use of inhaled corticosteroids at conventional doses carries a minor risk of adverse effects. Risks include thrush, the development of cataracts, and a slightly slowed rate of growth. Rinsing the mouth after the use of inhaled steroids can decrease the risk of thrush. Higher doses of inhaled steroids may result in lower bone mineral density.

Others
Inflammation in the lungs can be estimated by the level of exhaled nitric oxide. The use of exhaled nitric oxide levels (FeNO) to guide asthma medication dosing may have small benefits for preventing asthma attacks but the potential benefits are not strong enough for this approach to be universally recommended as a method to guide asthma therapy in adults or children.When asthma is unresponsive to usual medications, other options are available for both emergency management and prevention of flareups. Additional options include:

Humidified Oxygen to alleviate hypoxia if saturations fall below 92%.
Corticosteroid by mouth are recommended with five days of prednisone being the same 2 days of dexamethasone. One review recommended a seven-day course of steroids.
Magnesium sulfate intravenous treatment increases bronchodilation when used in addition to other treatment in moderate severe acute asthma attacks. In adults intravenous treatment results in a reduction of hospital admissions. Low levels of evidence suggest that inhaled (nebulised) magnesium sulfate may have a small benefit for treating acute asthma in adults. Overall, high quality evidence do not indicate a large benefit for combining magnesium sulfate with standard inhaled treatments for adults with asthma.
Heliox, a mixture of helium and oxygen, may also be considered in severe unresponsive cases.
Intravenous salbutamol is not supported by available evidence and is thus used only in extreme cases.
Methylxanthines (such as theophylline) were once widely used, but do not add significantly to the effects of inhaled beta-agonists. Their use in acute exacerbations is controversial.
The dissociative anesthetic ketamine is theoretically useful if intubation and mechanical ventilation is needed in people who are approaching respiratory arrest; however, there is no evidence from clinical trials to support this.
For those with severe persistent asthma not controlled by inhaled corticosteroids and LABAs, bronchial thermoplasty may be an option. It involves the delivery of controlled thermal energy to the airway wall during a series of bronchoscopies. While it may increase exacerbation frequency in the first few months it appears to decrease the subsequent rate. Effects beyond one year are unknown.
Monoclonal antibody injections such as mepolizumab, dupilumab, or omalizumab may be useful in those with poorly controlled atopic asthma. However, as of 2019 these medications are expensive and their use is therefore reserved for those with severe symptoms to achieve cost-effectiveness. Monoclonal antibodies targeting interleukin-5 (IL-5) or its receptor (IL-5R), including mepolizumab, reslizumab or benralizumab, in addition to standard care in severe asthma is effective in reducing the rate of asthma exacerbations. There is limited evidence for improved health-related quality of life and lung function.
Evidence suggests that sublingual immunotherapy in those with both allergic rhinitis and asthma improve outcomes.
It is unclear if non-invasive positive pressure ventilation in children is of use as it has not been sufficiently studied.

Alternative medicine
Many people with asthma, like those with other chronic disorders, use alternative treatments; surveys show that roughly 50% use some form of unconventional therapy. There is little data to support the effectiveness of most of these therapies.
Evidence is insufficient to support the usage of vitamin C or vitamin E for controlling asthma. There is tentative support for use of vitamin C in exercise induced bronchospasm. Fish oil dietary supplements (marine n-3 fatty acids) and reducing dietary sodium do not appear to help improve asthma control. In people with mild to moderate asthma, treatment with vitamin D supplementation may reduce the risk of asthma exacerbations, however, it is not clear if this is only helpful for people who have low vitamin D levels to begin with (low baseline vitamin D). There is no strong evidence to suggest that vitamin D supplements improve day-to-day asthma symptoms or a persons lung function. There is no strong evidence to suggest that adults with asthma should avoid foods that contain monosodium glutamate (MSG). There have not been enough high-quality studies performed to determine if children with asthma should avoid eating food that contains MSG.Acupuncture is not recommended for the treatment as there is insufficient evidence to support its use. Air ionisers show no evidence that they improve asthma symptoms or benefit lung function; this applied equally to positive and negative ion generators. Manual therapies, including osteopathic, chiropractic, physiotherapeutic and respiratory therapeutic maneuvers, have insufficient evidence to support their use in treating asthma.  The Buteyko breathing technique for controlling hyperventilation may result in a reduction in medication use; however, the technique does not have any effect on lung function.  Thus an expert panel felt that evidence was insufficient to support its use. There is no clear evidence that breathing exercises are effective for treating children with asthma.

Prognosis
The prognosis for asthma is generally good, especially for children with mild disease. Mortality has decreased over the last few decades due to better recognition and improvement in care. In 2010 the death rate was 170 per million for males and 90 per million for females. Rates vary between countries by 100 fold.Globally it causes moderate or severe disability in 19.4 million people as of 2004 (16 million of which are in low and middle income countries). Of asthma diagnosed during childhood, half of cases will no longer carry the diagnosis after a decade. Airway remodeling is observed, but it is unknown whether these represent harmful or beneficial changes. Early treatment with corticosteroids seems to prevent or ameliorates a decline in lung function. Asthma in children also has negative effects on quality of life of their parents.

Epidemiology
In 2019, approximately 262 million people worldwide were affected by asthma and approximately 461,000 people died from the disease. Rates vary between countries with prevalences between 1 and 18%. It is more common in developed than developing countries. One thus sees lower rates in Asia, Eastern Europe and Africa. Within developed countries it is more common in those who are economically disadvantaged while in contrast in developing countries it is more common in the affluent. The reason for these differences is not well known. Low and middle income countries make up more than 80% of the mortality.While asthma is twice as common in boys as girls, severe asthma occurs at equal rates. In contrast adult women have a higher rate of asthma than men and it is more common in the young than the old. In 2010, children with asthma experienced over 900,000 emergency department visits, making it the most common reason for admission to the hospital following an emergency department visit in the US in 2011.Global rates of asthma have increased significantly between the 1960s and 2008 with it being recognized as a major public health problem since the 1970s. Rates of asthma have plateaued in the developed world since the mid-1990s with recent increases primarily in the developing world. Asthma affects approximately 7% of the population of the United States and 5% of people in the United Kingdom. Canada, Australia and New Zealand have rates of about 14–15%.The average death rate from 2011 to 2015 from asthma in the UK was about 50% higher than the average for the European Union and had increased by about 5% in that time. Children are more likely see a physician due to asthma symptoms after school starts in September.Population-based epidemiological studies describe temporal associations between acute respiratory illnesses, asthma, and development of severe asthma with irreversible airflow limitation (known as the asthma-chronic obstructive pulmonary disease "overlap" syndrome, or ACOS). Additional prospective population-based data indicate that ACOS seems to represent a form of severe asthma, characterised by more frequent hospitalisations, and to be the result of early-onset asthma that has progressed to fixed airflow obstruction.

Economics
From 2000 to 2010, the average cost per asthma-related hospital stay in the United States for children remained relatively stable at about $3,600, whereas the average cost per asthma-related hospital stay for adults increased from $5,200 to $6,600. In 2010, Medicaid was the most frequent primary payer among children and adults aged 18–44 years in the United States; private insurance was the second most frequent payer. Among both children and adults in the lowest income communities in the United States there is a higher rate of hospital stays for asthma in 2010 than those in the highest income communities.

History
Asthma was recognized in ancient Egypt and was treated by drinking an incense mixture known as kyphi. It was officially named as a specific respiratory problem by Hippocrates circa 450 BC, with the Greek word for "panting" forming the basis of our modern name. In 200 BC it was believed to be at least partly related to the emotions. In the 12th century the Jewish physician-philosopher Maimonides wrote a treatise on asthma in Arabic, based partly on Arabic sources, in which he discussed the symptoms, proposed various dietary and other means of treatment, and emphasized the importance of climate and clean air.In 1873, one of the first papers in modern medicine on the subject tried to explain the pathophysiology of the disease while one in 1872, concluded that asthma can be cured by rubbing the chest with chloroform liniment. Medical treatment in 1880 included the use of intravenous doses of a drug called pilocarpine. In 1886, F </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Lutembachers syndrome and can you explain it in depth? [/INST] Lutembachers syndrome is a very rare form of congenital heart disease that affects one of the chambers of the heart (commonly the atria) as well as a valve (commonly the mitral valve). It is commonly known as both congenital atrial septal defect (ASD) and acquired mitral stenosis (MS). Congenital (at birth) atrial septal defect refers to a hole being in the septum or wall that separates the two atria; this condition is usually seen in fetuses and infants. Mitral stenosis refers to mitral valve leaflets (or valve flaps) sticking to each other making the opening for blood to pass from the atrium to the ventricles very small. With the valve being so small, blood has difficulty passing from the left atrium into the left ventricle. Septal defects that may occur with Lutembachers syndrome include: Ostium primum atrial septal defect or ostium secundum which is more prevalent.Lutembachers syndrome affects females more often than males. It can affect children or adults; the person can either be born with the disorder or develop it later in life. The syndrome was first described by René Lutembacher (1884–1968) of Paris in 1916.To correct Lutembachers syndrome, surgery is often done. There are several types of surgeries depending on the cause of Lutembachers syndrome (ASD Primum or ASD Ostium Secundum with Mitral Stenosis):

Suturing (stitching) or placing a patch of tissue (similar to skin grafting) over the hole to completely close the opening
Reconstructing of the mitral and tricuspid valve while patching any holes in the heart
Device closure of ASD (e.g. Amplatzer umbrella or CardioSEAL to seal the hole)
Percutaneous transcatheter therapy
Transcatheter therapy of balloon valvuloplasty to correct MS

Symptoms and signs
As Lutembachers syndrome is known for ASD and MS, most of the symptoms experienced will be associated with ASD and MS. For most people, they will remain asymptomatic (experience no symptoms) but when symptoms are shown, they are due mainly to ASD and will vary depending on the size of the hole in the atria. If the patient has a large ASD, pulmonary congestion (blood or fluid buildup in the lungs) will happen later but if the patient has a small ASD, symptoms will appear early in the disorder. In general, unless the ASD and mitral stenosis causing Lutembachers syndrome is severe, symptoms may not appear until the second and third decade of the patients life. As many of the patients are asymptomatic and symptoms may not appear until later in life, the duration or frequency of the symptoms varies. For symptoms such as palpitations, ventricular overload, heart failure, and pulmonary congestion, these symptoms may be sudden and not that frequent as they are very severe symptoms. For symptoms such as loud mitral S1, pulmonary S2, mid-diastolic murmur, fatigue, reduced exercise tolerance, weight gain, ankle edema, and right upper quadrant pain, and ascities, these symptoms may be less frequent and severe; their duration may be only a few seconds, minutes, or even months.

Major symptoms
Major symptoms of Lutembachers syndrome as a result of ASD and MS can range from heart failure to pulmonary congestion.
Right ventricular overload and Right-sided heart failure: Both are caused by a large ASD and MS (moderate to severe).
Palpitations: This is caused by blood flowing from left atrium to the right atrium causing a higher left atrial pressure and leading to mitral stenosis. Both atria will be dilated (stretched or open) leading to future atrial arrhythmias or atrial fibrillation (Riaz).
Pulmonary congestion: When blood or fluid pools within the lungs; this is usually a symptom of mitral stenosis and a small ASD.
Loud mitral S1 and wide fixed split of pulmonary S2: The loud sound of the mitral S1 and the wide fixed split of pulmonary S2 is a symptoms of mitral stenosis. The sounds often are caused by a reduced pressure gradient in the mitral area that was caused from decompression of the left atrium from the ASD and a displacement (moving from normal position) of the left ventricular lower portion of the heart to the a large right ventricle. The second heart sound (S2) split is caused by the increase right heart blood flow through the ASD causing a late closing of the pulmonary component of the S2 as well as decreased left ventricular and aortic blood flow.
III/IV mid diastolic murmur, early systolic murmur: This heart murmur is caused by an increase blood flow through the tricuspid valve due to ASD; it is heard best in the left lower sternal area or the bottom of the heart (apex).

Minor symptoms
Fatigue: symptoms is caused by decreased systemic (oxygenated blood to the rest of the body) flow. When the patient has MS and the blood flows from the left atrium to the right atrium causes the forward blood flow into the left ventricle to reduce leading to a reduction of systemic blood flow; this causes tiredness.
Reduced exercise tolerance: symptoms also caused by decreased systemic (oxygenated blood to the rest of the body) flow. Just as with fatigue, when the patient has MS and the blood flows from the left atrium to the right atrium, the forward blood flow into the left ventricle is reduced leading to a reduction of systemic blood flow; this causes tiredness and hence a reduced exercise tolerance.
Weight gain: this is commonly found in patients with large ASD and can be a symptom of developing right-sided heart failure. As there is a chronically increased left-to-right blood flow through the atria, this will lead in the future to right-sided heart failure.
Ankle edema: This is also caused by a large ASD and has the same symptoms and causes as seen in weight gain and right upper quadrant pain. As blood flow is not happening correctly and the heart is pumping under strain, pooling of blood and fluid will happen in the ankles.
Right upper quadrant pain: Also caused by large ASD; has same symptoms and underlying causes as weight gain and ankle edema.
Ascites: Ascite is known as abnormal buildup of fluid in spaces between abdomen lining and abdominal organs. Same symptoms and causes as weight, gain, ankle edema, and right upper quadrant pain.

Less common symptoms
Paroxysmal nocturnal dyspnea, orthopnea, and hemoptysis (sign of pulmonary venous congestion): this symptoms are less frequent in Lutembachers syndrome and are more associated with MS and small ASD or patients who develop reverse Lutembachers syndrome. This symptom is caused by mitral stenosis.

Related disorders
Eisenmenger syndrome
Ventricular Septal Defect
Mitral regurgitation
Ebstein disease

Causes
Lutembacher is caused indirectly by heart damage or disorders. Lutembachers syndrome is caused by either birth defects where the heart fails to close all holes in the walls between the atria or from an episode of rheumatic fever where damage is done to the heart valves such as the mitral valve and resultant in an opening of heart wall between atria. With Lutembachers syndrome, a fetus or infant is usually seen to have a hole in their heart wall (interatrial) separating their right and left atria.  Normally during fetal development, blood bypasses the lungs and is oxygenated from the placenta. Blood passes from the umbilical cord and flows into the left atrium through an opening called the foramen ovale; the foramen ovale is a hole between the two atria. Once a baby is born and the lungs begin to fill with air and the blood flow of the heart changes, a tissue flap (somewhat like a trap door) called the septum primum closes the foramen ovale or hole between the two atria and becomes part of the atrial wall. The failure of the hole between the two atria to close after birth leads to a disorder called ASD primum. The most common problems with an opening found in the heart with Lutembachers syndrome is Ostium Secundum. Ostium Secundum is a hole that is found within the flap of tissue (septum primum) that will eventually close the hole between the two atria after birth. With either type of ASD, ASD will usually cause the blood flow from the right atrium to skip going to the right ventricle and instead flow to the left atrium. If mitral stenosis (the hardening of flap of tissue known as a valve which opens and closes between the left atrium and ventricle to control blood flow) is also present, blood will flow into the right atrium through the hole between the atria wall instead of flowing into the left ventricle and systemic circulation. Eventually this leads to other problems such as the right ventricle failing and a reduced blood flow to the left ventricle.In addition to the ASD, MS can either be acquired (present either from an episode of rheumatic fever or the mother has or had rheumatic fever during the pregnancy) or congenital (the child being born with the disorder). With the combination of both ASD and MS, the heart can be under severe strain as it tries to move blood throughout the heart and lungs.

Mechanism
There is no exact mechanism for Lutembachers syndrome but instead a combination of disorders as the result of Atrial septal defect (ASD) and/or Mitral valve stenosis.It is thought ASD is caused by the failure to close the hole (foramen ovale) between the right and left atrium normally found within the heart during fetal development; the creation of a hole between the atrium may also be acquired. There are two types of ASD: Ostium secundum and ASD Primum.

Atrial Septal Defect Primum
The failure of the hole between the right and left atrium to close shortly after birth is the cause behind ASD primum. During fetal development blood will pass from the umbilical cord and flow into the left atrium through a hole between the two atria. Once a baby is born and the lungs begin to fill with air, the blood flow of the heart changes; a tissue flap (septum primum) normally closes the hole (foramen ovale) between the two atria and becomes part of the atrial wall. During ASD primum, after birth the hole is not completely closed allowing blood to flow into the right atria from the left atria. Then blood pass to right ventricle this will increase pulmonary artery pressure  Due to the incorrect blood flow, symptoms such as fatigue (from decreased systemic blood flow), palpitations (from blood flowing from left atria to right atria), weight gain, edema, right upper chest pain (all caused from the left to right atria blood flow), and paroxysmal nocturnal dyspnea (shortness of breath during sleep), orthopnea (difficulty in breathing while lying down), and hemoptysis or coughing up blood (all caused by small ASD that cause blood flow from left to right atria).

Atrial Septal Defect Ostium secundum
During the more common form of Lutembachers syndrome, ASD Ostium secundum, a hole will form in the flap of tissue (septum primum) that should close between the two atria after birth. With the onset of a hole created in the tissue flap that closes the larger hole between the left and right atrium, blood can again flow from the left atrium to the right. Ostium secundum causes many of the same symptoms seen in ASD primum. With either type of ASD, blood will flow from the right atrium skipping the right ventricle (or very little flowing into the ventricle) and instead flow to the left atrium introducing the possibility of blood lacking oxygen to go the rest of the body. Sometimes, the direction of blood flow is largely determined by the left and right ventricle ability to squeeze (contract) and relax (compliance).Apart from congential or birth defects causing ASD, ASD is thought to be also acquired. During percutaneous interventional procedures such as mitral valvuloplasty (a surgical process done to repair a mitral valve), 11-12% of individuals will develop ASD allowing blood to flow from the left atrium to the right.

Mitral Valve Stenosis
The second cause of Lutembachers syndrome is mitral stenosis (MS). MS can be caused by birth defects, rheumatic fever, or just stress to the heart due to ASD; because MS can be caused by several things, there is no exact mechanism but many mechanisms or causes. If mitral valve stenosis is a result of birth defects during development stemming from rheumatic fever, several things may occur in the heart. Rheumatic fever causes the immune system to attack its own protein tissues leading to lesions forming on the mitral valve flaps. As the flaps heals over time, the flaps lose their filmy and floppiness resulting in solid, stiff flaps. The loss of proper flappy mitral valves makes it harder for the valves to open and allow blood to flow through. As a result of blood flow being stopped or slowed by the faulty valve, pressure begins to build in the heart. It was once thought an ASD is not already present, could form because of MS, but it is now thought the ASD is either a birth defect or acquired from surgical procedures.Overall, Lutembachers syndrome has no certain mechanism but a combination as the result of ASD and MS.

Diagnosis
Lutembachers syndrome is diagnosis primarily by physical examinations for heart sounds, electrocardiograms, chest radiogram, transthoracic or transesophageal echocardiography, color flow mapping, and Doppler imaging. Use of the various test can help to differentiate other possible conditions such as mitral regurgitation, Ebstein disease, ventricular septal defect (VSD).

Physical examinations
A physical examination will be done to check for abnormal heart sounds, condition of heart, blood pressure, lungs, palpitations, edema, weight gain, ascites, or any other abnormal symptoms. Blood may also be drawn to help determine the cause of fatigue, determination of ascites, other health problems that maybe closely related to cause the symptoms such as kidney, liver, immune (signs of rheumatic fever), abnormal glucose levels.

Electrocardiograms
Electrocardiogram (ECG) is used for determination of the location, size, direction of blood flow through the atrial hole, hemodynamic of the right ventricle (blood circulation), tricuspid valve, and functioning of left ventricle. The ECG can also be used to determine the rhythm of the heart to determine if there is an indication of sinus rhythm or atrial fibrillation. In the ECG, the p wave morphology will be study for any abnormalities. If during the ECG, the P-wave (atrial depolarization) is tall, broad, or split waves in lead II and accompanied with a deep negative force in V1, this would be considered to be abnormal; only one wave should be associated with the P-wave. Additionally, in an ECG the QRS morphology and axis will be examined for any abnormalities. If the ECG shows a right axis deviation which is abnormal or a right bundle-branch block (this would mean there was no signal going through the atrium to instruct the ventricle to contract or squeeze blood out of the ventricle).

Chest radiogram
A chest radiogram can be given to a patient to determine:
Pulmonary plethora: the test will help to determine if there is a left-to-right shunt meaning the blood is flowing from the left atrium to the right through a hole between the two atria.
Mild left atrial enlargement: the test will help to determine if the left atrium is enlarged due to alternate blood flows
Right ventricular enlargement: the test will help to determine if the ventricle is enlarged due to a surge of blood above normal or if the ventricle is having to work harder than normal to pump blood out of the ventricle.
Pulmonary artery enlargement: the test will help to determine if there is a large volume of blood in the pulmonary veins and arteries than normal
Mitral Valve calcification late in life: the test will help to determine if the mitral valve or flaps are becoming hardened and losing their floppiness.
pulmonary vascular congestion, marked left atrial enlargement: the test will help to determine if there is a sign of MS and small ASD and how severe both are.

Transthoracic or Transesophageal echocardiography
Transthoracic or Transesophageal echocardiography two dimensional images that can be made of the heart. They can be used to determine the stages of Lutembachers syndrome. They are used to determine:

Large left atrium: the test can help to determine if the left atrium is enlarged to a large blood flow then unusually
Large right atrium and ventricle: the test will help to determine if the right atrium and ventricle are enlarged due to a greater blood flow
ASD: the test will help to determine if there is a hole between the two atria and if blood is flowing through both
Stenotic mital valve: the test will help to determine if the blood flow through the mitral valve is normal or if the mitral valve is stiff, has a reduced opening, and constricting blood flow through it.

Color flow mapping and Doppler imaging
A color flow and doppler imaging is used to help confirm the presence as well as evaluate the severity of ASD and MS.

Chest X-ray
A chest x-ray will be given to determine the size of the heart and the blood vessels supplying blood to the lungs.

Cardiac catheterization
Cardiac catheterization is done to confirm a diagnosis; it is not routinely done prior. It can also be used to evaluate the severity of ASD and measure the mitral valve area. To determine the presence ASD, a catheter is passed through the suspected hole between the atrium into the left atrium.

Treatments
To treat Lutembachers syndrome, the underlying causes of the disorder must first be treated: mitral stenosis and atrial septal defect. Lutembachers syndrome is usually treated surgically with treatments such as:
percutaneous transcatheter therapy for MS
Device closure of ASDPercutaneous transcatheter treatment for the MS can include transcatheter therapies of such as balloon valvuloplasty.

Percutaneous transcatheter therapy
Percutaneous transcatheter therapy is used to repair the mitral valve and sometimes the septum. In percutaneous balloon mitral valvuloplasty, using a catheter, a ballon such as the Inoue ballon is placed into blood vessels in the groin area and the balloon guided to the heart. If a hole is not already present, a small hole may need to be inserted the atria and inserted into the mitral valve through the left atrium; the balloon is then inflated. The balloon inside the mitral valve will be inflated and deflated several times to wide the valve opening until the opening is satisfactory; the balloon will then be deflated and removed.The advantage to using percutaneous procedures instead of open-heart surgery is not needing general anesthesia, blood transfusions, and the recovery time is quicker. The drawback to this procedure is the lack of repeating and transseptal procedures if they are needed later. Also if the patient later develops a relapse of MS, surgery will need to be performed where using more evasive techniques. Additionally, if a hole is needed to be inserted into the atria to obtain access to the mitral valve, there is a risk of developing ASD secondarily.

Side effects
Possible side effects from this non-invasive procedure could be:
fever
Chest pain
Shortness of breath
Unusual swelling or weight gain
Swelling, bleeding, change in skin color at site of initial catheterization in groin, or pain in the groin.If any of the above symptoms occur, it is important to contact your doctor to prevent another lapse of mitral stenosis. To ensure good health, routine doctors visits, diet, weight loss, doctor-approved exercise, and use of antibiotics in dental and other procedures are recommended.

Device closure
To treat ASD a device closure can be used. In fact an ASD closure is often recommended for certain cases such as with a patient who has significant left-to-right shunt with a pulmonary and/or systemic flow fraction of Qp/Qs >1.5. It is best to perform this procedure/surgery between the ages of 2–4 years. The closure is done by two methods: interventionally or surgically.

Interventionally
This procedure is done by placing a device such as Amplatzer "umbrella", CardioSEAL similar to percutaneous transcatheter therapy. A catheter is inserted in the vessels and threaded to the heart and inserted into the ASD closing the defect. Other closure device that have been used is the GORE HELEX Septal Occluder. After the device has been inserted and covers the defect, over time tissue will grow over the implant device to make it become part of the heart. Anticoagulant medication will be given to the patient for the first six months following the surgery: aspirin, clopidogrel or warfarin (Coumadin).

Surgically
This procedure is done through open heart surgery (sternotomy or thoracotomy) using an ECC where the heart is stopped to allow a system of special cannulas to be placed. The hole is closed by a direct suture (sewing) if the hole is small enough or if the hole is larger, suturing (sewing) a small patch of pericardium (heart tissue or skin) or fabric to close the hole.To increase quality life following ASD procedures/surgeries, patients should have a physical exam and ECG every 3, 6, and 12 months with their cardiologist. For many patients with secundum ASD closure repair, they can return to their normal activities unless their procedure was heart catheterization which in this case they should rest for a few days. All patients should remain on blood thinner medication for at least 6 months and up to a year unless the patient had a stroke in which they would always be on blood thinners. Patients with coronary artery disease or pulmonary hypertension will take additional medicines described by their physician. For patients who had heart surgery to repair the defect or received a transcatheter closure device, they will need to take some form of antibiotics to prevent infections such as endocarditis for at least 6 months following the procedure.Success with ASD closure is very high, 96% for percutaneous procedures and 100% of ASD surgeries as found by one research group. No patient was found to have died from either interventional or surgical treatments and only 7.2% of patients
who received a device and 24.0% of patients who had surgery had complications. The hospital stay for each group also varied, the surgical group was 3.4 ± 1.2 days and device group 1.0 ± 0.3 days. As seen by this study, prognosis was good and quality of life could be excellent.

Side effects
Side effects with interventional device closure have not been extensively supported as yet.Possible side effects from the ASD device closure procedure could be:
fever
Chest pain
Swelling
Swelling, bleeding, change in skin color at site of initial catheterization in groin, or pain in the groinWith surgically closure, the normal risk of infection, fevers, and blood clots are among the risks. If any signs of infection such as swelling, pain, or fever are present, the patient should seek medical attention </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Leontiasis ossea and can you explain it in depth? [/INST] Leontiasis ossea, also known as leontiasis, lion face or lion face syndrome, is a rare medical condition, characterized by an overgrowth of the facial and cranial bones. It is not a disease in itself, but a symptom of other diseases, including Pagets disease, fibrous dysplasia, hyperparathyroidism and renal osteodystrophy.The common form is that in which one or other maxilla is affected, its size progressively increasing, and thus encroaching on the cavities of the orbit, the mouth, the nose and its accessory sinuses. Exophthalmos gradually develops, going on later to a complete loss of sight due to compression of the optic nerve by the overgrowth of bone. There may also be interference with the nasal respiration and with the taking of food. In the somewhat less common form of this rare disease the overgrowth of bone affects all the cranial bones as well as those of the face, the senses being lost one by one and death finally resulting from cerebral pressure. There is no treatment other than exposing the overgrown bone, and chipping away pieces, or excising entirely where possible.

Great Sphinx
Surgeon Hutan Ashrafian from Imperial College London has analysed the Great Sphinx to identify that it may have represented an individual suffering from prognathism which may have been a reflection of a disease suffered by the sculptures human inspiration. Furthermore, as the Sphinx represented a lion, the same person may have suffered from leontiasis ossea.

See also
Lionitis

References

This article incorporates text from a publication now in the public domain: Chisholm, Hugh, ed. (1911). "Leontiasis Ossea". Encyclopædia Britannica </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is T-cell prolymphocytic leukemia and can you explain it in depth? [/INST] T-cell-prolymphocytic leukemia (T-PLL) is a mature T-cell leukemia with aggressive behavior and predilection for blood, bone marrow, lymph nodes, liver, spleen, and skin involvement. T-PLL is a very rare leukemia, primarily affecting adults over the age of 30. It represents 2% of all small lymphocytic leukemias in adults. Other names include T-cell chronic lymphocytic leukemia, "knobby" type of T-cell leukemia, and T-prolymphocytic leukemia/T-cell lymphocytic leukemia.

Signs and symptoms
People affected by T-cell prolymphocytic leukemia typically have systemic disease at presentation, including enlargement of the liver and spleen, widespread enlargement of the lymph nodes, and skin infiltrates.Due to the systemic nature of this disease, leukemic cells can be found in peripheral blood, lymph nodes, bone marrow, spleen, liver, and skin.  A high lymphocyte count (> 100 x 109/L) along with low amounts of red blood cells and platelets in the blood are common findings. HTLV-1 serologies are negative, and serum immunoglobins are within normal limits with no paraproteins present.

Causes
It is postulated that the originating cell line for this disease is a mature (post-thymic) T-cell.

Diagnosis
Morphology
In the peripheral blood, T-PLL consists of medium-sized lymphocytes with single nucleoli and basophilic cytoplasm with occasional blebs or projections. The nuclei are usually round to oval in shape, with occasional patients having cells with a more irregular nuclear outline that is similar to the cerebriform nuclear shape seen in Sézary syndrome. A small cell variant comprises 20% of all T-PLL cases, and the Sézary cell-like (cerebriform) variant is seen in 5% of cases.Marrow involvement is typically diffuse with morphology similar to what is observed in peripheral blood. In the spleen, the leukemic cell infiltrate both the red pulp and white pulp, and lymph node involvement is typically diffuse through the paracortex </s>