AsthmaAsthma

Review of Pathophysiology and Treatment

Definition Definition

It is a chronic inflamatory disorder due to hyperresponsiveness of airways characterized by dysponea, cough,wheezing and chest tightness with variable airway obstruction.

Types Types

Early onset asthma Late onsetasthma Nocturnal asthma Brittle asthma Cardiac asthma Catamenial

asthma Cough variant asthma Aspirin sensitive asthma Occupational asthma

Child-onset asthma Child-onset asthma

– Associated with atopy– IgE directed against common

environmental antigens (house-dust mites, animal proteins, fungi

– Viral wheezing Infants/children, allergy/allergy history associated with continuing asthma through childhood

Adult-onset asthma Adult-onset asthma

– Many situations– Allergens important – Non-IgE asthma have nasal polyps,

sinusitis, aspirin sensitivity or NSAID sensitivity

– Idiosyncratic asthma less understood

Adult-onset asthma Adult-onset asthma

– Occupational exposure animal products, biological enzymes, plastic

resin, wood dusts, metal removal from workplace may improve

symptoms although symptoms persist in some

Pathophysiology Pathophysiology

Airway limitation usually reversible Airway hyperreactivity Airway inflamation

With increased severity and chronicity remodelling,fibrosis and fixed narrowing of airways and decreased response to drugs.

Airway Inflammation Airway Inflammation

More often triggered by infections and chronic allergies.

IgE mediated triggering mast cell release.

Causes “fixed” obstruction not responsive to albuterol and more often has an inspiratory component.

Strong genetic contribution.

Needs steroids.

Airway hyperresponsiveness Airway hyperresponsiveness

Primarily smooth muscle mediated.

Can occur at any age.

Reversible with albuterol. Primarily expiratory wheezes.

Results in air trapping / obstruction (can be quantified on PFT’s).

Variable throughout lungs. May cause atelectasis on x-ray.

Primary process for wheezing due to cold air, exercise, pet allergens.

Airflow limitation Airflow limitation

– Acute bronchoconstriction IgE -dependent mediator release from mast

cell (leukotrienes, histamine, tryptase, prostaglandins)

aspirin /NSAID non-IgE response (cold air, exercise, irritants)

Airflow limitation– Chronic mucus plug formation

secretions & inspissated plugs persistent airflow limitation in severe intractable

asthma

– Airway remodeling irreversible component of airflow limitation

secondary to structural airway matrix changes

A Closer LookA Closer Look

Etiology Etiology

Environmental(hygeine hypothesis)

Genetical

Common TriggersCommon Triggers

Infections: viral respiratory illness (rhinovirus, influenza, RSV, parainfluenza, human metapneumovirus), sinus infections

Allergens: seasonal allergens, indoor allergens, pets

Irritants: cigarette smoke, wood smoke, other pollutants, weather changes

Diagnosis Diagnosis

Compatible history plus either/or FEV more than15% following

bronchodilator therapy. More than 20% diurnal variation on

PEFR diary for 3 days a week for 2 weeks.

FEV more than 15% decrease after 6 minutes of exercise.

Differential Diagnosis Differential Diagnosis

Upper RTI Lower RTI Systemic

Asthma ClassificationAsthma Classification

Mild intermitten

t

Day symptoms < 2/week, Night symptoms < 2/month Normal FEV , FEV/FVC normal

Mild persistent

Day symptoms >2 per week but not daily,Night symptoms> 3-4/month Normal FEVFEV/FVC normal

Moderate persistent

Daily symptoms, affect activity,night symptoms > 1/weekFEV60-80%FEV/FVC reduced < 5%

Severe persistent

Continuous symptoms, limited activity,

FEV <60%FEV/FVC reduced >5%.

Investigation Investigation

Lab investigations Radiology Spirometry PEFR recording

Pharmacologic TherapyPharmacologic Therapy

Long-term control medications (Controllers) Short term control medications (Relievers)

– corticosteroids inhaled form systemic steroids used to gain prompt control

of disease when initiating inhaled tx

– cromolyn sodium or nedocromil mild-to-moderate anti-inflammatory medications

(may be used initially in children) preventive tx. prior to exercise or unavoidable

exposure to known allergens

Management Management

AccordingtoGINA,NAEPP3,WHO,NHI, NHLBI guidelines management should

be in 4 steps. Assess and monitor asthma severity

and control Patient education Environmental control Medical therapy

Pharmacologic TherapyPharmacologic Therapy

Long-term control medications– corticosteroids

inhaled form systemic steroids used to gain prompt control

of disease when initiating inhaled tx

– cromolyn sodium or nedocromil mild-to-moderate anti-inflammatory medications

(may be used initially in children) preventive tx. prior to exercise or unavoidable

exposure to known allergens

Relievers Relievers

Beta adrenergic agonists. Anticholinergic agents Phosphodiesterase inhibitors Corticosteroids Antimicrobials

Controllers Controllers

Anti inflamatory agents (steroids) Long acting bronchodilators Mediator inhibitors Beta adrenergic agonists Phosphodiesterase inhibitors

Leukotrienes modifiers Desensitization drugs Vaccinations Miscellaneous agents

Long-term control medications Long-term control medications

– Long-acting beta2-agonists used concomitantly with anti-inflammatory

meds for long-term symptom control especially nocturnal symptoms

prevents exercise-induced bronchospasm

– Methylxanthines sustained-release theophylline used as

adjuvant to inhaled steroids for prevention of nocturnal symptoms

Long-term control medications Long-term control medications

– Leukotriene modifiers zafirlukast - leukotriene receptor antagonist zileuton - 5-lipoxygenase inhibitor is alternative

therapy to low doses of inhaled steroids/nedocromil/cromolyn

alternative tx to low dose inhaled steroids/cromolyn/nedocromil

recommended for >12yrs with mild persistent asthma.

Quick relief medications Quick relief medications

– Short acting beta2-agonists - relief of acute symptoms

– Anticholinergics - may provide additive benefit to beta2 drugs in severe exacerbation. May be alternative to beta2-agonists

– Systemic steroids - moderate-to-severe persistent asthma in acute exacerbations or to prevent recurrence of exacerbations

Treatment/Long Term ControlTreatment/Long Term Control

Corticosteroids– Most potent and effective– Reduction in symptoms, improvement in

PEF and spirometry, diminished airway hyperresponsiveness, prevention of exacerbations, possible prevention of airway wall remodeling

– Suppresses: cytosine production, airway

eosinophilic recruitment, chemical mediators

LABA LABA

Long-acting beta-2 agonists– Relax airway smooth muscle– Duration of action >12 hrs– Not used in acute exacerbations– Adjunct to anti-inflammatory tx for long-

term symptom control especially nocturnal symptoms

Methylxanthines Methylxanthines

– Provides mild-moderate bronchodilation– Low dose has mild anti-inflammatory action– Sustained release form used as alternative

but not preferred to long-acting beta2 agonists to control nocturnal symptoms

– Use may be necessary because of cost or patient compliance

Leukotriene modifiers Leukotriene modifiers

– Leukotrienes are potent biochemical mediators released from mast cells, eosinophils, and basophils that:

contract bronchial smooth muscle increase vascular permeability increase mucus secretions attract & activate inflammatory cells in airways

Leukotriene modifiers Leukotriene modifiers

– Zafirlukast & zileuton (oral tabs) improves lung fx and diminishes symptoms &

need for short-acting beta2 agonists

– Studies in mild-moderate asthma showing modest improvements

– Alternative to low-dose inhaled steroids for pts. with mild persistent asthma

– Further study in of other groups needed

Asthma Treatment/Quick ReliefAsthma Treatment/Quick Relief

Short-acting beta2 agonists – Relax airway smooth muscle and increase

in airflow in <30 minutes– Drug of choice for treating symptoms and

exacerbations and EIB– Use of >1 canister/mo indicates

inadequate control and indicates need to intensify anti-inflammatory tx

– Regularly scheduled use NOT recommended

Anticholinergics Anticholinergics

– Cholinergic innervation important in regulation of airway smooth muscle tone

– Ipratropium bromide (quaternary derivative of atropine without its’ side effects)

– Additive benefit with inhaled beta 2-agonists in severe asthma exacerbations

– Effectiveness in long-term management not demonstrated

Systemic steroids– speed resolution of airflow obstruction– reduce rate of relapse

Medications to reduce oral steroid dependence– Troleandomycin, cyclosporin, gold,

methotrexate, IV immunoglobulin, dapsone, hydroxychloroquine

Intermittent AsthmaIntermittent Asthma

Step 1– Short-acting inhaled beta 2 agonists PRN

IF NEEDED >2 X/wk PATIENT SHOULD BE MOVED TO THE NEXT STEP OF CARE (exception is EIB or viral infections)

– Viral infections mild symptoms - beta 2 agonist Q 4-6 hr moderate-to-severe symptoms - short course of

systemic steroids recommended plus above

Persistent AsthmaPersistent Asthma

Mild, moderate or severe – Daily long-term control recommended

Mild persistent asthma (step 2 care)– Daily anti-inflammatory meds - inhaled

steroids (low dose) or cromolyn or nedocromil

– Sustained release theophylline alternative but not preferred

Moderate persistent asthma (step 3 care)– Increase inhaled steroids to medium dose

OR– Add long-acting bronchodilator to a low-

medium dose of inhaled steroids

OR– Increase to medium dose steroid then

lower dose & add nedocromil (+/-)

Moderate persistent asthma (if not adequately controlled)– Increase to high dose inhaled steroids &

add long-acting bronchodilator (serevent or theophylline)

Severe persistent asthma (step 4)– If not controlled on high dose of inhaled

steroids and long-acting bronchodilator ADD oral systemic steroids on a regularly scheduled, long-term basis

use lowest dose monitor closely attempt to reduce or take off when control

established

Complications Complications

Due to drugs Due to disease