This document discusses asthma in adults. It begins by providing statistics on asthma prevalence and costs in the US. It then describes asthma as a chronic inflammatory disease of the airways causing reversible airflow obstruction. The pathophysiology of asthma involves both intrinsic and extrinsic mechanisms. Extrinsic mechanisms are immune-related and involve mast cell activation by allergens. Clinical features of asthma include respiratory symptoms triggered by various factors that resolve with treatment. Diagnosis involves assessing symptoms, physical exam findings, and pulmonary function testing. Asthma is classified by severity to guide initial treatment and management. The document reviews various asthma medications and their mechanisms of action. It concludes by discussing management of asthma exacerbations in urgent care settings.
This document discusses asthma in adults. It begins by providing statistics on asthma prevalence and costs in the US. It then describes asthma as a chronic inflammatory disease of the airways causing reversible airflow obstruction. The pathophysiology of asthma involves both intrinsic and extrinsic mechanisms. Extrinsic mechanisms are immune-related and involve mast cell activation by allergens. Clinical features of asthma include respiratory symptoms triggered by various factors that resolve with treatment. Diagnosis involves assessing symptoms, physical exam findings, and pulmonary function testing. Asthma is classified by severity to guide initial treatment and management. The document reviews various asthma medications and their mechanisms of action. It concludes by discussing management of asthma exacerbations in urgent care settings.
This document discusses asthma in adults. It begins by providing statistics on asthma prevalence and costs in the US. It then describes asthma as a chronic inflammatory disease of the airways causing reversible airflow obstruction. The pathophysiology of asthma involves both intrinsic and extrinsic mechanisms. Extrinsic mechanisms are immune-related and involve mast cell activation by allergens. Clinical features of asthma include respiratory symptoms triggered by various factors that resolve with treatment. Diagnosis involves assessing symptoms, physical exam findings, and pulmonary function testing. Asthma is classified by severity to guide initial treatment and management. The document reviews various asthma medications and their mechanisms of action. It concludes by discussing management of asthma exacerbations in urgent care settings.
May 2014 Introduction 1 in 12 people in the U.S. have asthma = 25 million people (CDC 2011) 7 million are children $56 billion per year in medical costs, missed school days and missed work days >3000 deaths due to asthma in the U.S. (2010) Numbers growing every year
What is Asthma? Chronic inflammatory disease of the airways causing airflow obstruction Obstructive lung disease Bronchial hyperresponsiveness Symptoms typically wax and wane REVERSIBLE (at least partially) Triad of: Bronchoconstriction Inflammation and edema of airway walls Mucus production/plugging
Asthma - Pathophysiology 2 mechanisms Intrinsic non-immune related, caused by vagal stimulation (e.g. viral infection, exercise, cold air) Extrinsic immune-related, caused by mast cell activation and degranulation (e.g. allergens) Asthma - Pathophysiology Extrinsic Allergens bound by dendritic cells and presented to T- and B-cells T-cells secrete cytokines causing B- cell production of IgE IgE coats mast cells; cross-linking causes mast cell degranulation and release of histamine, leukotrienes, and inflammatory cytokines
Asthma - Pathophysiology 2 phases of asthma attack Early phase Within several minutes Allergen exposure by sensitized individual causes mast cell degranulation and release of histamines, prostaglandins, leukotrienes, etc. Can also be through vagal stimulation by irritant Bronchoconstriction via smooth muscle contraction, edema via blood vessel dilation and increased permeability, and mucus production Late phase Hours later Recruitment of other inflammatory and immune cells, e.g. eosinophils, basophils, neutrophils, T-cells, monocytes, dendritic cells Further release of inflammatory mediators Clinical Features - History Respiratory symptoms in presence of triggers that resolve with avoidance of trigger or with asthma medication E.g. allergens, exercise, cold air, smoke, infection, aspirin Symptoms Wheeze Cough, often worse at night Dyspnea Chest tightness Symptoms typically episodic and often worse at night Personal or family history of asthma, allergies, or other atopic diseases History of chronic cough, nighttime cough, or recurrent bronchitis as a child Clinical Features Physical Scattered, high-pitched musical wheezes Commonly expiratory, but can also be inspiratory Usually varies in tone and duration over time, starts and stops at different points of respiratory cycle Severe Tachypnea Tachycardia Prolonged expiration (decreased I:E ratio) Tripod position Use of accessory muscles of respiration Pulsus paradoxus (decrease in SBP >12mmHg during inspiration) Absence of wheeze may indicate severe bronchoconstriction Extra-pulmonary Nares pale, swollen mucosa suggest of allergic rhinitis; nasal polyps suggest aspirin sensitivity Skin atopic dermatitis
Nasal polyps Diagnosis of Asthma History Physical exam Spirometry FEV1/FVC ratio <70% Increase in FEV1 >12% or 200ml with administration of short-acting bronchodilator (e.g. albuterol) Decrease in FEV1 >20% with bronchoprovocation test (methacholine or mannitol inhalation) Peak expiratory flow >20% variability over several recordings Other Studies CBC with diff may show eosinophilia (>15% or >1500/microL) CXR May show pneumonia (possible exacerbating factor) Also used to rule out other causes of asthma-like symptoms Poorly controlled asthma may have atelectasis due to mucus plugging Allergy tests identify triggers Total serum IgE when considering use of omalizumab as therapy Classifying Asthma Severity Intermittent Symptoms 2 days/week Nighttime awakenings 2x/month Use of short-acting beta 2 -agonist 2 days/week Mild persistent Symptoms >2 days/week but less than daily Nighttime awakenings 3-4x/month Use of short-acting beta 2 -agonist >2 days/week but not daily and not >1x/week Moderate persistent Symptoms daily Nighttime awakenings >1x/week but not nightly Use of short-acting beta 2 -agonist daily Severe persistent Symptoms throughout the day Nighttime awakenings often 7x/week Use of short-acting beta 2 -agonist several times a day
Classifying Asthma Severity & Initial Treatment Management of Asthma by Severity Reassessment and Adjusting Therapy Asthma Medications Asthma Medications Mechanisms of Action Asthma Medications Short-acting beta 2 -agonists (SABA) E.g. Albuterol, levalbuterol, pirbuterol, metaproterenol Use: PRN Mechanism: bronchial smooth muscle relaxation Side effects: increase HR, tremors, arrhythmias, irritability Levalbuterol marketed to have fewer side effects Long-acting beta-agonists (LABA) E.g. salmeterol, formoterol, arformoterol Use: usually added to treatment if moderate persistent asthma or worse. Used as twice daily controller Mechanism and side effects same as short-acting
Asthma Medications Inhaled corticosteroids (ICS) E.g. beclomethasone, budesonide, flunisolide, fluticasone, mometasone Use: added for mild persistent or worse. Twice daily controller Mechanism: decreases inflammation by inhibiting cytokine production Side effects: dysphonia, thrush, reflex cough Systemic corticosteroids E.g. prednisone, prednisolone, methylprednisolone (IV) Use: moderate to severe exacerbations. Usually given for 3-10 days to avoid adrenal suppression Side effects: adrenal suppression, leukocytosis, immune suppression, Cushings syndrome, neuropsychiatric disturbance, osteoporosis, cataracts Asthma Medications Anticholinergics E.g. ipratropium, tiotropium Use: in combination with SABA for mild/moderate persistent asthma Mechanism: inhibit muscarinic cholinergic receptors to reduce vagal tone bronchodilation Side effects: dry mouth, blurred vision, urinary obstruction Methylxanthines E.g. theophylline Use: add-on or alternative for moderate or severe persistent; used rarely Mechanism: inhibits phosphodiesterase, leading to increased cAMP smooth muscle relaxation Side effects: tachycardia, nausea/vomiting, sleep disturbance, arrhythmias and seizures in overdose; narrow therapeutic index Leukotriene modifiers E.g. montelukast, zafirleukast, zileuton Use: as alternative or add-on to ICS or LABA Mechanism: leukotriene receptor antagonist (montelukast, zafirleukast) or leukotriene synthesis inhibitor (zileuton). Leukotrienes responsible for eosinophil infiltration of airways Side effects: elevated transaminases, hepatotoxicity (zileuton)
Asthma Medications Mast cell stabilizers E.g. cromolyn, nedocromil Use: maintenance/controller. Add-on or alternate to ICS or LABA Mechanism: prevents activation and degranulation of mast cell by membrane stabilization (cromolyn) and prevents release of inflammatory mediators by by neutrophils, eosinophils, monocytes, and macrophages (nedocromil) Side effects: sore throat, unpleasant taste Anti-IgE E.g. Omalizumab Use: moderate to severe persistent asthma. Good for patients with allergies. Subcutaneous administration Mechanism: prevents IgE binding to mast cells Side effects: anaphylaxis
Urgent Care Setting Assessment Physical tachypnea, HR >120, diaphoresis, use of accessory muscles, inability to speak full sentences, pulsus paradoxus Peak flow meter PEF <200L/min or <50% of baseline Pulse oximetry ABG hypoxemia; normal or increased PaCO2 indicates worsening of exacerbation either by severe airway narrowing or inspiratory muscle fatigue Supplemental oxygen, albuterol, ipratropium, inhaled or IV steroids Maintain O s sat >90% Terbutaline drip or epinephrine Magnesium sulfate IV if patient unimproved on conventional therapy Bronchodilation by inhibition of calcium influx into smooth muscle cells If all else fails - Intubation and mechanical ventilation Methylxanthines, mast cell stabilizers, omalizumab, and LABAs are NOT effective in acute exacerbations References UptoDate FirstAid for USMLE Step 1 http://www.cdc.gov/nchs/fastats/asthma.htm Clinical Guideline for the Diagnosis, Evaluation and Management of Adults and Children with Asthma New York State Department of Health