Asthma overview

# Overview
Asthma is a chronic inflammatory disease that is characterized by a hyper-responsive airway and a resultant reversible airway obstruction. Approximately 5% of the total population have been diagnosed with asthma. Asthma affects one in four urban children. Asthmatics, a term used to characterize an individual affected with asthma, develop intermittent airway constriction and subsequent inflammation that is lined with excessive amounts of mucus as a response to one or more triggers. Environmental stimulants such as dust, cold air, mold, pollen and exercise or stress can trigger an asthmatic episode; however, in children, viral illness such as common cold remains the most common trigger. The classic symptoms include prolong expiratory wheeze, cough and shortness of breath secondary to airway obstruction that promptly responds to bronchodilator therapy. Between episodes most patients remain either, asymptomatic or have mild symptoms and may remain short of breath for longer periods after exercise. A positive bronchodilator response is strongly suggestive of asthma. Short-acting beta-2 agonist, inhaled anti-cholinergics and systemic steroids may be used for immediate symptomatic relief; however, long-term symptom control may be achieved with long-acting beta-2 agonists, mast cell stabilizers, leukotriene inhibitors and/or steroids.

# Historical Perspective
Asthma was first mentioned in Homer's Iliad. It was later studied by influential thinkers such as, Hippocrates, Galen, and Moses Maimonides. Asthma treatment methods emerged in the late 1800s.

# Classification
Asthma is classified into atopic and non-atopic types based on the onset of symptoms. Atopic refers to early-onset whereas non-atopic refers to late-onset. Despite the differentiation, a significant degree of overlap exists between the two types. The severity of symptoms is further classified based on the GINA severity grades into mild intermittent, mild persistent, moderate persistent and severe persistent asthma.

# Pathophysiology
Asthma is a chronic inflammatory disease of the airways that is characterized by reversible airflow obstruction and airway inflammation, persistent airway hyperreactivity, and airway remodeling. The two major factors responsible for the pathogenesis of asthma include bronchial hyper-responsiveness and inflammatory reaction within the bronchial wall. The airways of asthmatics are hypersensitive to certain triggers such as smoke, dust, or pollen. The term trigger is synonymous with stimuli. Exposure to these triggers causes repeated inflammation of the airways resulting in bronchospasm. Bronchospasm can lead to narrowing of airways and excess mucus production, making it difficult to breathe. Airway inflammation is a chronic inflammation driven by TH2 lymphocyte-predominant immune response. This immune response has been associated with atopy and IgE-synthesis through the production of IL-4 and eosinophilic inflammation by means of IL-5.

# Causes
Asthma is caused by a complex interaction of environmental and genetic factors that researchers do not yet fully understand. These factors can also influence how severe a persons asthma is and how well they respond to medication. As with other complex diseases, many environmental and genetic factors have been suggested as causes of asthma, but not all studies posing such claims have been verified by further studies. In addition, as researchers detangle the complex causes of asthma, it is becoming more evident that certain environmental and genetic factors may affect asthma only when combined.

# Differentiating Asthma from other Diseases
Asthma must be clinically differentiated from other conditions that cause recurrent cough and wheezing such as viral bronchiolitis, chronic obstructive pulmonary disease, congestive heart failure, vocal cord dysfunction, ACE inhibitors use and allergic rhinitis.

# Epidemiology and Demographics
Approximately 300 million people around the world currently have asthma and the number is estimated to increase by additional 100 million by the year 2025. Prevalence of asthma is high among children and females in industrialized nations. International Study of Asthma and Allergies in Childhood (ISAAC), which measured the global prevalence and severity of asthma symptoms in children, demonstrated that the high rates of asthma were noted in countries whose predominant language is English. Puerto Rican people have the highest prevalence of asthma in USA. Asthma accounts for 217,000 emergency room visits and 10.5 million physician office visits every year.

# Risk Factors
Asthma is usually diagnosed in childhood. Numerous risk factors such as gender, allergen exposure, airway hyper-reactivity have been identified to play a role in the development of asthma.

# Screening
The United States Preventive Services Task Force (USPSTF) has issued no guidelines for screening of asthma.

# Natural History, Complications and Prognosis
Wheezing may occur early in childhood. But in majority of cases, it may not persist into adulthood unless severe or has predisposition to asthma. Asthma progression during childhood vary with gender and may sometimes regress completely unlike adult onset asthma. Prognosis of asthma in absence of other co- morbidities is generally good with treatment and life expectancy is similar to that of general population. Complications of asthma may include status asthmaticus, respiratory failure, candidiasis and cardiac dysfunction.

# Diagnosis

## History and Symptoms
The clinical presentation of asthma varies with individuals both, with and without clinical therapies; meaning asthma can manifest as environmental stimulated or therapy-resistant. In some, asthma is characterized by chronic respiratory impairment while others experience episodic attacks secondary to a number of triggering events including: upper respiratory tract infection, stress, cold air, exercise, exposure to allergen (such as pets, dust, mites, pollen) or air pollutants (such as smoke or traffic fumes). The cardinal symptoms of asthma include loud expiratory wheeze, nocturnal cough and dyspnea. The majority of patients who develop asthma prior to adolescence may experience subsequent remission around puberty. These same asthmatics, however, have the potential for increased frequency of recurrences several years after puberty. Thereby, the National Asthma Education and Prevention Program emphasized the importance of assessment of frequency, severity, duration, limitations of daily activities and future risk of exacerbations to monitor the patient's level of asthma control.

## Physical Examination
The characteristic physical signs of asthma include: loud prolonged polyphonic expiratory wheeze and adventitious sounds such as rhonchi. Presence of wheeze is indicative of airway narrowing; however, the absence of wheeze indicates a silent lung characteristic of status asthmaticus delineated by widespread obstruction that results in significant airflow reduction and insufficient enough to produce a wheeze.

## Laboratory Findings
Routine laboratory tests are not indicated for the diagnosis of asthma but may be used to exclude other causes of wheeze. Elevated eosinophil count and elevated serum IgE levels may be observed in patients with a repeated history of allergic trigger. Arterial blood gas and pulse oximetry may be used to assess the disease severity and response to therapy.

## Electrocardiogram
ECG in asthmatics with acute severe exacerbation may reveal sinus tachycardia and a right heart strain pattern. However, the administration of a 2-agonist may relieve symptoms and hence result in a paradoxical decrease in heart rate. The presence of supraventricular tachycardia should raise a suspicion of theophylline toxicity.

## Chest X Ray
The chest x-ray in asthmatics is often normal. It is done to exclude other causes of wheeze and aid in the diagnosis of complications such as atelectasis and pneumonia.

## CT
In asthmatics, high-resolution CT may reveal several structural changes related to small-airway disease including cylindrical bronchiectasis, bronchial wall thickening, and air trapping. CT markers valid for small-airway disease can be derived from quantitative lung density measurements and these markers correlate with clinical severity, lung function test results and are also sensitive to demonstrate therapeutic effects. An FEV1/FVC ratio of 75% or more has been shown to be an important predictor of bronchial wall thickening and bronchiectasis; but has a low discriminatory utility for patients without structural airway changes (sensitivity, 67%; specificity, 65%). Thereby, suggesting the importance of radiological assessment of bronchial wall changes in patients with severe asthma.

## MRI
Functional MRIs help to measure the actual lung ventilation and localize the precise pathological area involved during an acute asthmatic attack. The use of special paramagnetic gases enhance the low signal-to-noise ratio of conventional spin-echo and gradient-echo techniques a several fold times, which in turn, abolishes the disadvantages induced by the air-alveolar interfaces.

## Other Imaging Findings
Radio-aerosol lung scintigraphy with technetium has been shown to precisely evaluate the extent of aerosol and particulate distribution and absorption through the entire air passage. In asthmatics receiving dry-powder inhalers as opposed to metered-dose inhalers, technetium scintigraphy may be used to demonstrate improved peripheral lung distribution of steroids. Ventilation defects may also be detected using technetium-99m DTPA.

## Other Diagnostic Studies

### Pulmonary Function Test
Asthma is defined as reversible airway obstruction that occurs both, spontaneously without intervention or even with treatment. Measurement of peak flow rates and spirometry are two valuable methods to assess pulmonary function. While measurement of airway function is possible in adults, most new cases that are diagnosed constitute the pediatric age group, who are unable to perform such tests. Diagnosis in children is based on a careful compilation and analysis of the individual's medical history and demonstration of symptomatic improvement with the administration of inhaled bronchodilator. In adults, diagnosis can be made with a peak flow meter that assess any airway restriction, diurnal variation and any reversibility following inhaled bronchodilator. Young asthmatics may experience only exercise-induced asthma; hence, testing peak flow at rest and after exercise may be beneficial. If in doubt, spirometry may be conducted to ascertain the diagnosis. Once the diagnosis is established, peak flow meter testing may be conducted to monitor the severity and progression of the disease. Capnography may be used in the emergency situations, to measure the amount of exhaled carbon dioxide and if used in conjunction with pulse oximetry may be possible to estimate the amount of oxygen dissolved in the blood, in order to determine the severity of an asthma attack as well as the predict the response to therapy.

### Bronchial Challenge Test
Asthmatics may remain asymptomatic for a long period unless provoked by a stimuli such as a chemical irritant, an environmental allergen, cold or dry air, or rigorous exercise that may precipitate an acute attack. The bronchial challenge test is a procedure performed to provoke airway obstruction using a stimuli that is known to trigger bronchospasm, sudden contraction of the bronchioles. This test helps to identify the specific environmental stimuli that triggers an acute attack and also helps to determine the extent of the reaction.

### Exhaled Nitric Oxide
Measurement of fractional nitric oxide concentration in exhaled breath (FeNO) is a non-invasive method of assessing underlying airway inflammation. However, due to technical complexities associated with the procedure, it is not routinely used.

# Treatment

## Emergency Management
Inhaled 2 agonist, such as albuterol, is the drug of choice for acute severe exacerbation of asthma. In cases of mild to moderate exacerbations, metered-dose inhalation (MDI) of a 2 agonist in conjunction with a spacer may be used. In more severe exacerbations, nebulized 2 agonist has been demonstrated to be most effective. In case of severe exacerbation with non- reponsiveness to 2 agonist inhalation/anticholinergic therapy, parenteral 2 agonist such as terbutaline may be administered. Ipratropium may also be utilized in cases of severe exacerbation. Steroid therapy remains the mainstay of therapy in the treatment of acute and sub-acute phases of exacerbation. Steroids speed in the resolution of airway obstruction and prevent a late-phase response; hence, shown to provide highly beneficial outcomes to patients with acute exacerbation presenting to the emergency department.

## Medical Therapy
Specific therapies available for the management of asthma are broadly classified into three groups: relievers, preventers and emergency treatment. The Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma (EPR-2) of the U.S. National Asthma Education and Prevention Program, and the British Guideline on the Management of Asthma are the two current guidelines that followed in the management of asthma. Bronchodilators are recommended for short-term relief in all patients. For those who experience occasional attacks, no other medication is needed. For those with mild persistent disease (more than two attacks a week), low-dose inhaled glucocorticoids or alternatively, an oral leukotriene modifier, a mast-cell stabilizer, or theophylline may be administered. For those who suffer daily attacks, a higher dose of glucocorticoid in conjunction with a long-acting inhaled -2 agonist may be prescribed; alternatively, a leukotriene modifier or theophylline may substitute for the -2 agonist. In severe asthmatics, oral glucocorticoids may be added to these treatments during severe attacks. For those in whom exercise can trigger an asthma attack (exercise-induced asthma), higher levels of ventilation and cold, dry air tend to exacerbate attacks.

## Alternative and Complementary Medicine
Asthmatic treatment therapies include both conventional pharmacological therapies and alternative, complementary medicinal therapies. Approximately 50% of asthma patients use some form of alternative, non-traditional therapies. There is little evidence to support these effectiveness of these therapies.

## Bronchial Thermoplasty
Bronchial thermoplasty is a new investigational outpatient procedure that is performed in the hospital bronchoscopy suite and is currently performed only in conjunction with the AIR2 Trial. The procedure uses controlled thermal energy to reduce the surface area of the smooth muscle in the bronchiole; thereby, helps to prevent future asthma attacks.

## Primary Prevention
The primary prevention of asthma includes efforts to reduce all personal exposure to tobacco smoke, including passive smoke exposure, occupational dusts and chemicals and other indoor and outdoor air pollutants linked to asthma.

## Secondary Prevention
The most effective treatment for asthma is identifying triggers, such as pets or aspirin, and limiting or eliminating exposure to them. Desensitization to allergens has been shown to be a treatment option for certain patients. As is common with respiratory disease, smoking is believed to adversely affect asthmatics in several ways, including an increased severity of symptoms, a more rapid decline of lung function, and decreased response to preventive medications. Automobile emissions are considered an even more significant cause and aggravating factor. Asthmatics who smoke or who live near traffic typically require additional medications to help control their disease. Furthermore, exposure of both non-smokers and smokers to wood smoke, gas stove fumes and second-hand smoke is detrimental, resulting in more severe asthma, more emergency room visits, and more asthma-related hospital admissions. Smoking cessation and avoidance of second-hand smoke is strongly encouraged in asthmatics.