Asthma

toc =Introduction to Asthma=
 * chronic inflammatory disorder
 * prevalence 3-5% of population
 * Often a childhood disease
 * 1/3 asthmatics diagnosed after age 30
 * 4000-5000 deaths per year in US!!

=Etiology= ifnlamatory mediators released from bronchial mast cells, T lymphocytes macrophages, epithelial cells mediators attract and activate other cells, eosinophils and neutrophils inflamation causes changes in epithelial integrity, autonomic tone, mucociliary function, smooth musle responsiveness >* increaed ccAMP **decreases** preformed mediator release >* increased cGMP **increases** preformed mediator release
 * often, tehre is a neural element to the inflammatory reaction
 * modulated by balance between cAMP and cGMP

Table of Intracellular Mediators Implicated in Asthma

 * Preformed Mediators||Synthesized Mediators||
 * histamine||Prostaglandin D2 & F2||
 * ECF||Leukotrienes B4, C4 & D4||
 * NCF||thromboxane||
 * Proteases|| Platelet Activcating factor, PAF||

overstimulation of sympathetic, or understimulation of parasympathetic tone may participate in asthma both types of nerves ennervate airway bronchodilative effects noted in: genetic factor: 43% concordance in 1st degree relatives Atopy is strongest risk factor
 * parasympathetic antagonists atropine
 * beta-adrenergic agonists albuterol

environmental catalysts
of asthmatic attack include ozone, nitrogen dioxidde, and industrial fumes, as well as viral infection.

other precipitators:
>* aspirin >* beta blockers >* NSAIDs
 * col air
 * exercise
 * environmantal allergns: pollens, molds, house dust, mites, animal danders
 * occupational chemical exposure
 * irrtants: tobacco smoke, strong odors, air pollutants
 * stress, fear, anger, frustration
 * crying or laughing
 * medications:
 * food adtives, **suflites**
 * hyperosmolarity

IgE cascadebest characterized but not only hyperinflammatory pathway implicated

cellular factors cause airway hyperreactivity, and bronchospasm

=Pathology=

triad asthma: ASA sensitivity, nasal polyps, sinusitis


 * chronic disease
 * variable duration, onset, severity
 * inflammation r swelling of airwways
 * increased sensitivity
 * temproary obstruction, or bronchospasm
 * excessive thick mucous
 * airflow obstruction
 * effect greatest at small airways (2mm and smaller)

microscopic signs

 * edema
 * thickened mucosal membrane
 * phlegm with eosinophils, crystals
 * hypertrophic smooth muscle
 * inflammation beteween mucosa, membrane

=Symptoms=
 * dyspnea
 * wheezing
 * coughing
 * chest tightniess
 * 'breathing through a straw'
 * acute attacks

=Signs= =Differential Diagnosis= underdiagnosis is frequient

Criteria

 * Episodic airway obstruction symptoms
 * obstruction partially or completely reversible

diagnosis of exclusion
>* incomplete endobroncial obstruction due to tumor, foreign body, or laryngeal dyskinesia >* emphysema >* chronic bronchitis
 * congestive heart failure with pulmonary edema
 * pulmonary embolism
 * carcinoid syndrome with bronchoconstrictive mediators
 * allergic rhinitis
 * sinusitis
 * cystic fibrosis
 * Chronic Obstructive Pulmonary Disease COPD

Diagnosis
>* Cough may be sole sign
 * history, history, history!


 * physical exam focusing on respiratory tract, chest, and skin
 * Pulmonary Function Testing, ideally involving spirometry before and after patient inhales a short-acting bronchodilator during an attack
 * can induce bronchoconstriction with methacholine, a cholinergic agonist
 * poor correlation with objective measures of lung function!


 * Peak Expiratory Flow Rate, PEFR is useful for monitoring, but not diagnosis


 * CXR useful only in exclusion

=Treatment=

Patient Education

 * don't be stupid
 * encourage adherence
 * r recognize symptoms of acute episodes
 * know common triggers
 * knowrelievers versus preventors
 * written guidelines and periodic review of inhler use is productive
 * avoid environmental triggers

Sympathetic Agonists

 * mechanisM: icnrease cAMP by stimlating adenylcyclase
 * aerosol is preferred delivery--minimizes systemic effects
 * selective beta 2 agonsits prefered: terbutaline, metaproterenol, albuterol
 * not preferred as much> epinephrine, isoproterenol

Methylxanthines

 * Theofphylline, aminophylline
 * bronchodilators
 * extrapulmonary effects--respiratory muscle contractility
 * preceise mechanism unclear
 * inhibit Phosphodiesterase, PDE in vitro, but physiological levels likely too low
 * synergistic effect with sympathetic agonists
 * often given IV in clinical setting due to variable absorption

Cholinergic Antagonists

 * potential relievers
 * poorly characterized in this role

Inhaled corticosteroids

 * beclomethasone
 * long term preventative therapy
 * deliver topically to tracheobronchial tree
 * minimal systemic effects

inhibition of leukotrienes

 * area of reaserch
 * Leukotriene D4 antagonists availlable: zafirlukast, montelukast

Mast Cell Stabilizers

 * Cromalyn
 * Nedocromil
 * prevenattive anti-inflammatory agnet

Oral Corticosteroids

 * drug of last resort

Supplemental Oxygen

 * may be lifesaving during acute attack

Antibiotics
if infection is indicated.