ASTHMA

Asthma: Chronic inflammatory disorder of the airways, characterized by episodic reversible bronchospasm
resulting from an exaggerated bronchoconstriction response to various stimuli
Is reversible bronchoconstriction; most common occupational disease
Classic asthma is mediated by IgE produced in a response to foreign antigen. IgE binds to mast cells in the
airway mucosa cause degranulation of mast cells when re-exposed releases other mediators such as
histamine, LKT, PG causes local smooth muscle contraction and vascular leakage
Intrinsic asthma: non-allergic mediated or elevation of IgE level. Triggered by respiratory infection. Skin antigen
test negative.)
Extrinsic asthma: is related to atopy (tendency to be hyperallergic) and type I hypersensitivity; characterized by
elevated serum IgE and family history
Drug induced asthma: (Example: Samters syndrome patients have symptoms consistent with asthma, nasal
polyps and sensitivity to aspirin or NSAIDs)
NSAIDs blocks PGs production and drives towards leukotrienes production. LT are bronchodilators and they
cause bronchospasm. In these patients, asthma can be improved by stopping the use of NSAIDs and starting
the use of Leukotriene receptor antagonists.
Exercise-Induced Bronchospasm: occurs immediately after exercise. Cooling and mucosal drying of airways
during exercise triggers mast cells to release histamine. Pre-treatment with beta agonist or cromolyn is effective.
Slow warm up period also helps.
Cough-variant asthma: cough without variable airway obstruction; history of chronic cough with irritants,
methacholine inhalation challenge test may aid defining the diagnosis
Nocturnal Asthma: asthma occurs at night during sleep (12am-8am) due to the decline of circulating
catecholamine and cortisol during that time
Allergic Bronchopulmonary aspergillosis: Type 3 IgE mediated response due to fungi Aspergillus fumigatus;
Treatment is prednisone
Clinical presentation: wheezing, cough, dyspnea, chest tightness (symptoms are often worse at night), sputum
Physical examination: audible wheezing and a prolonged expiratory phase
Diagnosis: reduced FEV1/FVC ratio; diurnal variation of Peak flow meter (PEFR) > 20% [ Normal: Highest PEFR
@4pm and lowest @4am]; 12% improvement & 200 cc increase (reversibility criteria), hyperinflation ( all volume
increased); normal to elevated DLCO (gas exchange) [vs. COPD where DLCO is reduced]
PATHO: Charcot-Leyden crystals (breakdown products of eosinophils), Curshmann spirals in sputum
Treatment: albuterol (B2 adrenergic agonist) for acute asthma attack (intermittent); For persistent asthma:
Inhaled corticosteroids long acting beta agonists (never use LABA by itself) leukotriene modifier

Others:

Airflow obstruction is determined by diameter of the airway lumen which can be altered by: edema, mucous,
airway SM contraction & hypertrophy, inflammatory cell infiltration, and airway remodeling (causes permanent
narrowing of airway due to subepithelial fibrosis)
Methacholine challenge Test has a high negative predictive value (excellent to rule out). Patient inhales
methacholine which cause the airways to spasm (contract) and narrow if asthma is present. If the lung function
drops by at least 20%, the test is considered positive. Bronchodilator is given at the end to reverse the effect.
Asthma Management

Adrenergic agonists Bronchodilator

B2 specific, quick onset-short duration: Albuterol, Terbutaline
B2 specific, slow onset-long acting: Salmeterol, Formoterol [ only used in combination with inhaled steroids]

Cholinergic antagonist Bronchodilator

Atropine, Ipratropium, Tiotropium, Umedclidinum

Methylxanthines Bronchodilators and anti-inflammatory

Theophylline, Aminophylline

Chromolyns anti-inflammatory
Cortocosteriod anti-inflammatory
LRBA: Montelukast, Zafirlukast
Anti-IgE antibodies: Omalizumab and Dupilumb
Anti-IL5 antibodies: Mepolizumab, Reslizumab

M3 receptor stimulation will not only cause bronchoconstriction, it may also predispose patients to be in
proinflammatory stage.
Summary: B2 agonist increases level of cAMP cAMP activates PKA that phosphorylates MLCK This decreases MLCK
activity smooth muscle relaxation
***Long term use of B-agonists will cause an uncoupling of the receptor from G protein can activate PLC and thus
increased inflammation

COPD

Progressive loss of airflow in lungs resulting in broncho-constriction that is not fully reversible.
Mechanism: Elastic parenchymal tissue is replaced by fibrotic tissue such that elastic of lung is lost. Collapse of
airway mid-exhalation leads to air trapping, loss of capacity and impaired gas exchange.
2 common forms are bronchitis and emphysema