Asthma Review of Pathophysiology and Treatment
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