Asthma

A syndrome defined by an inflammation (usually allergen induced)  of the airways of the respiratory system; thus causing excessive constriction  of these airways.  The  National Asthma Education and Prevention Program Expert Panel defines asthma as "a common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation.

Affects approximately 300 million people worldwide, making it one of the most common chronic diseases globally.  Can present at any age, but peak age of onset is 3 years.

The pathophysiology of asthma is complex, with several interacting inflammatory cells which result in acute and chronic effects on the airway.  There is no key cell that is predominant.

-  Mast cells are exposed to certain allergen and activated through an IgE dependent mechanism.  Mast cells in turn release several bronchonstricting mediators including histamine, prostaglandin D2, leukotrienes.

- Along with mast cells, eosinophils, T helper cells, basophils, neutrophils, and platelets are inflammatory cells that also induce many downstream mediators.

- These inflammatory mediators in turn cause such effects such as bronchospasm, plasma exudation, mucus secretion, and long term airway structural changes.

Asthma has a multitude of causes, usually a complex interplay between genetic and environmental factors.  The major risk factor for asthma is atopy, with patients usually suffering from other atopic diseases such as allergic rhinitis.

There are several other risk factors that predispose one to asthma such as genetics, gender, ethnicity, obesity, environmental exposure to allergens.  May also arise from nonallergic causes such as exercise, viral infection, irritants (household spray paint fumes), cold air, aspirin intolerant asthma, and occupational exposures.

The most common signs and symptoms are shortness of breath, wheezing, chest tightness, and cough.  These vary over time and together limit the airflow of expiration.  Symptoms may be worse at night, and patients typically awaken in the early morning hours with cough and shortness of breath.  There is increased mucus production that can be difficult to expectorate. These are nonspecific symptoms, and can sometimes make it difficult to distinguish from other respiratory diseases.

There is no definitive laboratory test to diagnose asthma.  Asthma cannot be diagnosed until after the age of 2, as before this age children usually have wheezing induced by viral infections.  Clinically, the symptoms of asthma are nonspecific, and can be made based on history and physical exam. Undergoing outpatient pulmonary function tests will help clue into the diagnosis.

Physical exam findings will include findings of increased work of breathing, increased respiratory rate, and expiratory wheezing on pulmonary auscultation.

Treatment of asthma is divided into bronchodilators and controller medications.

Bronchodilators include:

           1) Beta 2 agonists (albuterol and terbutaline) - activate the beta 2 receptors (widely expressed in airways), which promotes smooth muscle relaxation of the airways. They also inhibit inflammatory cells such as mast cells.

           2) Anticholinergics (ipratropium) - prevent cholinergic induced bronchoconstriction and mucus secretion.

           3) Theophylline - oral bronchodilator (induces smooth muscle relaxation), which has fallen out of favor due to side effects and not usually given.

Controllers:

           1) Inhaled corticosteroids - the most effective anti-inflammatory agents, reduce inflammatory cell numbers and their activation in the airways.

           2) Systemic corticosteroids (hydrocortisone, methylprednisolone, prednisone, or prednisolone) used in the treatment of acute asthma exacerbations.

           3) Antileukotrienes (montelukast) - block the inflammatory effects of leukotrienes

           4) Cromones (cromolyn sodium and nedocromil) - inhibit mast cells.

           5) Anti IgE (omalizumab) - antibody that neutralizes circulated IgE, inhibiting IgE mediated reactions.