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Allergic Asthma

Disease Details

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Description: Allergic asthma is a type of asthma triggered by allergens such as pollen, dust mites, mold, or pet dander, causing airway inflammation and difficulty breathing.
Type: Allergic asthma, also known as atopic asthma, does not follow a simple pattern of genetic transmission. It is considered a complex genetic disorder, meaning that multiple genes, along with environmental factors, contribute to the development of the condition. There is a hereditary component, as having a family history of asthma or other allergic conditions like eczema or hay fever increases the risk. However, the exact mode of inheritance is multifactorial rather than strictly Mendelian.
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.
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. More recent data find that severe asthma can result in airway remodeling and the "asthma with chronic obstructive pulmonary disease syndrome (ACOS)" that has a poor prognosis. 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.
Onset: Allergic asthma can often begin in childhood, but it can occur at any age. It is typically triggered by allergens such as pollen, dust mites, mold spores, pet dander, or certain foods. The onset may follow exposure to these allergens and can be associated with other allergic conditions like eczema or allergic rhinitis.
Prevalence: The prevalence of allergic asthma varies by region, but it is estimated to affect approximately 10-20% of people with asthma worldwide. It is particularly common in children and young adults.
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.
Intractability: Allergic asthma is not considered intractable. While it is a chronic condition and there is currently no cure, it can be effectively managed with medications, lifestyle changes, and avoidance of triggers. Treatment options such as inhaled corticosteroids, bronchodilators, and allergy immunotherapy can help control symptoms and improve quality of life.
Disease Severity: Allergic asthma severity can vary widely among individuals. It ranges from mild, where symptoms are infrequent and easily managed with minimal medication, to severe, where symptoms are persistent, difficult to control, and may significantly impact daily life. Severe cases often require more intensive treatment and can lead to frequent hospitalizations.
Healthcare Professionals: Disease Ontology ID - DOID:9415
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.
Carrier Status: Allergic asthma is not a condition with a carrier status, as it is not inherited in a simple Mendelian fashion like recessive genetic diseases. There is no "carrier" state for allergic asthma. It can, however, have a genetic component, meaning individuals with a family history of allergies or asthma are at higher risk.
Mechanism: Allergic asthma is a chronic inflammatory disease of the airways characterized by recurring symptoms, airflow obstruction, and bronchospasm, triggered by allergens. It involves complex interactions between environmental and genetic factors.

**Mechanism:**
1. **Sensitization:** When an allergen is first encountered, it is taken up by antigen-presenting cells (APCs), such as dendritic cells, which process and present the allergen to T-helper 2 (Th2) cells.
2. **Activation:** Th2 cells release cytokines like interleukin-4 (IL-4), IL-5, and IL-13, which promote B cells to switch to IgE production.
3. **IgE Response:** IgE antibodies specific to the allergen bind to high-affinity receptors (FcεRI) on the surface of mast cells and basophils.
4. **Re-exposure:** Upon subsequent exposure to the same allergen, cross-linking of bound IgE on mast cells and basophils triggers the release of histamines, leukotrienes, and other mediators.
5. **Inflammation and Bronchoconstriction:** These mediators cause airway smooth muscle contraction, increased mucus secretion, and recruitment of other inflammatory cells like eosinophils, leading to inflammation, airway hyperresponsiveness, and asthmatic symptoms.

**Molecular Mechanisms:**
1. **Cytokines and Chemokines:** Th2 cytokines such as IL-4, IL-5, and IL-13 are critical for the differentiation, survival, and recruitment of eosinophils. IL-4 and IL-13 are involved in IgE class switching.
2. **IgE and FcεRI:** IgE binds to FcεRI receptors on mast cells and basophils, leading to degranulation upon allergen exposure.
3. **Mast Cell Mediators:** Release of histamines, prostaglandins, and leukotrienes results in bronchoconstriction, vasodilation, and mucus production.
4. **Eosinophilic Inflammation:** Eosinophils release cytotoxic granules, cytokines, and reactive oxygen species, contributing to tissue damage and chronic inflammation.
5. **Airway Remodeling:** Chronic inflammation leads to structural changes in the airways, including subepithelial fibrosis, increased smooth muscle mass, and angiogenesis, which contribute to irreversible airway obstruction over time.

Understanding these mechanisms is crucial for developing targeted therapies to manage allergic asthma effectively.
Treatment: For allergic asthma, treatment typically includes:

1. **Avoiding Triggers:** Minimizing exposure to allergens such as pollen, dust mites, pet dander, and mold.
2. **Medications:**
- **Inhaled Corticosteroids:** Reduce inflammation in the airways (e.g., fluticasone, budesonide).
- **Long-acting Beta Agonists (LABAs):** Relax muscles around the airways (e.g., salmeterol, formoterol).
- **Leukotriene Modifiers:** Reduce airway inflammation and constriction (e.g., montelukast).
- **Combination Inhalers:** Contain both corticosteroids and LABAs.
- **Biologic Therapies:** Target specific pathways in the allergic response (e.g., omalizumab, mepolizumab).
- **Rescue Inhalers:** Short-acting bronchodilators for immediate relief of symptoms (e.g., albuterol).
3. **Allergy Shots (Immunotherapy):** Gradual exposure to allergens to reduce sensitivity.
4. **Lifestyle Changes:** Regular exercise, maintaining a healthy weight, and avoiding smoking.
5. **Monitoring and Follow-Up:** Regular check-ups with a healthcare provider to monitor asthma control and adjust treatment as necessary.

Always consult with a healthcare provider to determine the most appropriate treatment plan for individual needs.
Compassionate Use Treatment: Compassionate use treatments for allergic asthma may involve investigational drugs not yet approved by regulatory authorities but deemed potentially beneficial for severe cases with no other treatment options available. These might include certain biologics or novel therapies undergoing clinical trials.

Off-label or experimental treatments can include:

1. **Biologics**: Medications like omalizumab (Xolair), mepolizumab (Nucala), reslizumab (Cinqair), benralizumab (Fasenra), and dupilumab (Dupixent) are typically approved for severe asthma and might be used off-label for specific allergic asthma cases.
2. **Bronchial Thermoplasty**: A procedure that uses heat to reduce the airway's smooth muscle mass, aiming to decrease constriction during asthma attacks.
3. **Immunotherapy**: Allergen immunotherapy or allergy shots, which gradually increase the exposure to allergens to build up tolerance.
4. **Fevipiprant**: An investigational drug targeting prostaglandin D2 receptor, currently in trials for uncontrolled asthma.
5. **New biologics targeting other interleukins**: Agents targeting IL-4, IL-5, or IL-13 are under investigation for their potential efficacy in allergic asthma.

These treatments require careful consideration and monitoring by a healthcare provider due to their experimental or off-label status.
Lifestyle Recommendations: Lifestyle recommendations for managing allergic asthma include:

1. **Identifying and Avoiding Triggers**: Identify allergens that trigger asthma symptoms, such as pollen, dust mites, pet dander, mold, and certain foods. Take steps to avoid exposure to these allergens.

2. **Maintain a Clean Environment**: Regularly clean your living space to reduce allergens. Use HEPA filters in your vacuum and air purifiers. Wash bedding in hot water weekly and use allergen-proof mattress and pillow covers.

3. **Medication Adherence**: Follow your doctor's advice on asthma medications, including maintenance inhalers and rescue inhalers. Consistent use of prescribed medications can help control inflammation and prevent symptoms.

4. **Healthy Diet**: Maintain a balanced diet rich in fruits, vegetables, and whole grains. Avoid foods that you're allergic to.

5. **Regular Exercise**: Engage in regular physical activity to improve lung function, but choose exercises that don't trigger your asthma. Warm up properly and avoid exercising outdoors during high pollen days or in cold, dry air.

6. **Stress Management**: Practice stress-reducing techniques such as yoga, meditation, or deep-breathing exercises, as stress can exacerbate asthma symptoms.

7. **Smoking Cessation**: Avoid smoking and exposure to secondhand smoke, as tobacco smoke can worsen asthma symptoms.

8. **Monitor Air Quality**: Pay attention to local air quality forecasts and limit outdoor activities when air quality is poor.

9. **Regular Check-Ups**: Schedule regular visits with your healthcare provider to monitor your asthma and make necessary adjustments to your treatment plan.

10. **Vaccinations**: Stay up-to-date with vaccinations, especially flu and pneumonia vaccines, as respiratory infections can worsen asthma.

11. **Emergency Plan**: Have an action plan for asthma attacks, including knowing how to use your rescue inhaler and when to seek emergency medical care.
Medication: 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.
Repurposable Drugs: Allergic asthma is a type of asthma triggered by allergens such as pollen, pet dander, or dust mites. Some repurposable drugs that can be used to manage allergic asthma include:

1. **Montelukast**: Originally developed for asthma, it's also used for allergic rhinitis.
2. **Omalizumab**: Initially for severe allergic asthma, it targets IgE antibodies.
3. **Azithromycin**: An antibiotic with anti-inflammatory properties useful in some asthma cases.
4. **Methotrexate**: An immunosuppressant sometimes used in severe asthma.
5. **Statins**: Primarily used to lower cholesterol, they have anti-inflammatory effects that may benefit asthma patients.

It is crucial to consult a healthcare provider for appropriate diagnosis and treatment strategies.
Metabolites: Allergic asthma is characterized by inflammatory processes involving the immune response to allergens. Key metabolites associated with allergic asthma include:

1. **Eicosanoids** (e.g., leukotrienes and prostaglandins) - These are inflammatory mediators that play a significant role in the bronchoconstriction and inflammation seen in allergic asthma.
2. **Histamine** - Released from mast cells, it contributes to bronchoconstriction, mucous secretion, and vascular permeability.
3. **Arachidonic Acid** - A precursor to eicosanoids, this fatty acid is involved in the inflammatory cascade of allergic asthma.
4. **Cysteinyl Leukotrienes (CysLTs)** - Derived from arachidonic acid, these play a key role in bronchoconstriction, mucous production, and edema in asthma.
5. **Periostin** - A matricellular protein that has been identified as a biomarker for eosinophilic inflammation in asthma.

These metabolites are part of the pathological process in allergic asthma, contributing to symptoms such as airway constriction, inflammation, and increased mucus production.
Nutraceuticals: Allergic asthma is a type of asthma triggered by allergens. Various nutraceuticals have been investigated for their potential benefits in managing allergic asthma, including omega-3 fatty acids, vitamin D, quercetin, and probiotics. These substances may help reduce inflammation, modulate the immune response, and improve overall lung function.

Nanotechnology also shows promising applications in allergic asthma, such as targeted drug delivery systems using nanoparticles. These systems can enhance the efficacy and reduce the side effects of conventional asthma medications by delivering them directly to the site of inflammation in the lungs.
Peptides: In allergic asthma, peptides and nanoparticles (nan) have been studied for their potential therapeutic applications. Peptides can act as immunomodulators to reduce airway inflammation and hyperresponsiveness by targeting specific components of the immune response. Nanoparticles can be used to deliver drugs or therapeutic agents directly to the lungs, enhancing the efficacy and reducing side effects of treatments.