Asthma overview

Editor(s)-in-Chief: C. Michael Gibson, M.S., M.D. [mailto:mgibson@perfuse.org] Phone:617-632-7753; Philip Marcus, M.D., M.P.H. [mailto:pmarcus192@aol.com]; ;

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.

Pathophysiology
Asthma is the result of an immune response in the bronchial airways. . During an asthma episode, inflamed airways react to the introduction of environmental triggers, such as smoke, dust, or pollen. The airways narrow and produce excess mucus, making it difficult to breathe.

The airways of asthmatics are "hypersensitive" to certain triggers, also known as stimuli. In response to exposure to these triggers, the bronchi (large airways) contract into spasm (an "asthma attack"). Inflammation soon follows leading to a further narrowing of the airways and excessive mucus production, this can lead to coughing and other breathing difficulties.

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. The International Study of Asthma and Allergies in Childhood (ISAAC), a study 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.

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 person’s 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.

Natural History, Complications and Prognosis
Wheezing may occur early in childhood. In the majority of cases, unless severely asthmatic or predisposed to asthmatic symptoms, wheezing may not persist into adulthood. Asthma progression during childhood varies with gender and may sometimes regress completely. In contrast, in some cases, a patient may experience adult onset asthma. Prognosis of asthma, in the absence of other co-morbidities, is generally positive with treatment and life expectancy being similar to that of the comparable general population. Complications of asthma may include status asthmaticus, respiratory failure, candidiasis and cardiac dysfunction.

History and Symptoms
The clinical presentation of asthma varies with individuals both spontaneously and with therapy. In some, asthma is characterized by chronic respiratory impairment and 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
 * Dyspnea
 * Chest tightness
 * Stridor in the absence of a wheeze may be confused with a COPD-type of disease and hence it is difficult to diagnose asthma based upon the history alone.

Majority of patients develop asthma prior to adolescence with subsequent remission around puberty and increased frequency of recurrences then after for several years. 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 through use of multiple measures.

Physical Examination
The characteristic physical signs of asthma include loud prolong 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 Tests

 * A markedly elevated serum eosinophil count greater than 15% may suggest an underlying allergic disease.
 * Arterial blood-gas is used to evaluate the respiratory function. It may be reserved to patients with severe acute exacerbation of asthma. In severe acute exacerbation, ABG may reveal respiratory alkalosis that is consistent with the hypoxemia and/or hypercarbia secondary to significant hypoventilation.
 * A normal total serum IgE level does not exclude the diagnosis of asthma; however in a patient with recurrent episodes secondary to allergen exposure, may report positive for allergic tests and is associated with a higher positive predictive value.
 * Skin testing is another method that may be used to assess the allergic sensitivity to specific aero-allergens such as dust, pollen and mold spores.

Pulmonary Function Test
Asthma is defined as reversible airway obstruction that occurs spontaneously or with treatment. Measurement 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. Thereby, 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, the sudden contraction of the bronchioles. This test helps to identify the specific environmental stimuli that triggers acute attacks and also helps to determine the extent of the reaction.

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

Chest X-ray
Chest x-ray in asthmatics is often normal. Chest x-ray is often used to exclude other causes of wheeze and to diagnosis complications, such as atelectasis and pneumonia.

Chest 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. 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.

Treatment
There is no cure for asthma; however, medications could help to prevent future attacks and relieve the symptoms such as tightness of the chest and trouble breathing.

The specific medical treatment recommended depends on the severity and the frequency of exacerbations. Specific therapies available for the management of asthma are broadly classified into three groups namely, 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 are 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 β-2 agonist may be prescribed; alternatively, a leukotriene modifier or theophylline may substitute for the β-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. For this reason, activities in which a patient breathes large amounts of cold air, such as skiing and running, tend to be worse for asthmatics, whereas swimming in an indoor, heated pool, with warm, humid air, is less likely to provoke a response.


 * Long-acting bronchodilators (LABA) are similar in structure to short-acting selective beta2-adrenoceptor agonists, but have much longer sidechains resulting in a 12-hour effect, and are used to give a smoothed symptomatic relief (used morning and night). While patients report improved symptom control, these drugs do not replace the need for routine preventers, and their slow onset means the short-acting dilators may still be required.