Asthma Primer

Wayne Kradjan, Pharm. D.

Definition of Asthma

• A chronic inflammatory disorder of the airways…

• In susceptible individuals, this inflammation causes episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or early morning.

• Usually associated with widespread but variable airflow obstruction (bronchospasm) that is often reversible, either spontaneously or with treatment.

• Inflammation also causes an increase in bronchial hyperresponsiveness to a variety of stimuli (triggers)

Large, “central” airways

Small, “peripheral”

AirwaysOnly site of

gas exchange

Causes of Airflow Obstruction

• Bronchospasm- Hyperresponsiveness and narrowing of airways (bronchi) due to muscle spasm.

• Airway edema (swelling of walls)

• Mucous plugging

• All made worse by airway inflammation

Bronchial Hyperresponsiveness

• More easily induced bronchospastic response to a variety of stimuli that may not otherwise cause a response in the general population.– Allergens– Chemicals, irritants– Exercise

• Response may also be more intense and prolonged

• Non-asthma patients may develop a transient BHR after viral upper respiratory infection.

Asthma Triggers

• Allergens (seasonal/ perennial)– Grass, weeds, pollen, mold, mildew– Animal dander, saliva, dust mites

• Chemical irritants and fumes– Cigarette smoke, pollution, perfume– Household cleaners, occupational

• Viral infections, rhinitis, sinusitis, (“post nasal drip”)

• Gastroesophageal reflux (GERD)• Exercise; cold, dry air• Extreme emotions• Drugs (aspirin, beta blockers)

Measuring Airflow Obstruction

• Assessing air outflow– Peak flow: Maximum rate

(L/min) of airflow out of the lung during a forced exhalation.

– FEV1: Forced expiratory volume in one second. Actual volume (L) of air expired in the first second of a forced exhalation.

– FVC: Forced vital capacity. Total volume of air expired during a forced exhalation.

Peak Flow Meter

Obstructive Airways Disease: Sequence of Events

Inflammation, nerve exposure

Hyperresponsiveness

“Trigger”: allergen or irritant exposure(cold air, exercise)

Bronchospasm ( FEV1, peak flow)mucous, edema, cough

OBSTRUCTION

Epidemiology• 5% of US population• 5,000 deaths per year in US• Higher incidence in inner city,

especially African Americans and Hispanic populations.– Racial vs. socioeconomic?

Environmental Factors

• Increased time spent indoors– Indoor allergens (molds, mites,

cockroaches) • Tobacco smoke exposure

– maternal smoking risk for child• Increased childhood infections

associated with lower risk– Having older or multiple

siblings or day care center attendance may lower risk (more childhood infection)

– Hygienic hypothesis

Childhood onset• Most common chronic disease of

children (6.9% of population)

– More likely to be allergic basis

– Common: child with positive family history of asthma and allergy to tree and grass pollen, house dust mites, household pets and molds.

– 30-70% markedly improve or symptom free as adult

Adult onset• May be allergic or non-allergic• Often negative family history and

negative skin tests to common allergens

• Often history of nasal polyps, aspirin sensitivity and chronic sinusitis

• Environmental exposure: wood dust, chemicals, pollutants at workplace or in air

• Chemical sensitizers: viral infection, tobacco smoke, diet, perfume

Expert Panel 2 Report

Guidelines for the Diagnosis and Management of Asthma

NIH Publication #97-4051A

National Institutes of Health.National Heart, Lung and Blood Institute

May 1997

http://www.nhlbi.nih.gov/guidelines/index.htm

Schering, Astra-Zeneca, or Glaxo-Wellcome

Update on Selected Topics 2002

Guidelines for the Diagnosis and Management of Asthma

NIH Publication #02-5075

National Institutes of Health.National Heart, Lung and Blood Institute

November 2002

http://www.nhlbi.nih.gov/guidelines/asthma/asthsumm.htm

J Allergy Clin Immunol. 2002;110:S1-S219 (Nov supplement)

Step Approach to Classification• Mild Intermittent

– Sxs <2/week, PM sxs < 2/month

– PFTs >80%, < 20 variability

• Mild Persistent– Sxs 3-6x/ week; PM sxs 3-4/month

– PFTs >80%, 20-30% variability

• Moderate Persistent– Sxs daily; PM sxs > 5 per/month

– PFTs 60-80%, >30% variability

• Severe Persistent– Sxs continual; PM sxs frequent

– PFTs <60%, >30% variability

• Acute exacerbations

Staging:Further Considerations

• Seasonality• Nocturnal symptoms• Exercise induced• Peak flow monitoring• Daily fluctuations• Cough variant• “Wheezy bronchitis” in

children

“Reliever”, “Rescue” Drugs• Rapid acting bronchodilators

– beta adrenergic agonists– intermediate duration (3-6 hrs)

» Often called “short acting”

– metered dose inhaler (MDI),dry powder inhaler (DPI, breath actuated),solution for nebulization

• Albuterol (salbutamol) (Proventil, Ventolin)

• Levalbuterol (Xopenex)• Bitolterol (Tornalate)• Metaproterenol (Alupent, Metaprel)• Pirbuterol (Maxair)• Terbutaline (Bricanyl, Brethine)• (Epinephrine, isoproterenol, isoetharine)

Metered Dose InhalerAlbuterol (Proventil HFA)

Air Jet Nebulizer

Anticholinergicbronchodilators• Ipratropium (Atrovent)

Tiotropium (Spiriva)• MDI (Atrovent and Spiriva)

– Also combination with albuterol: Combivent

• Solution for nebulization (Atrovent)– Also combination with albuterol:

DuoNeb (500 mcg/2.5 mg)

• Slower onset, longer acting than albuterol– Atrovent QID; Spiriva QD

• Dry mouth and blurred vision• Greater role in COPD than in asthma

“Controller” Drugs:Antiinflammatory

• Inhaled corticosteroids– Beclomethasone (Beclovent, Vanceril)– Budesonide (Pulmicort)

(Turbuhaler, and Respules)– Flunisolide (Aerobid, Aerobid M)– Fluticasone (Flovent)

(Advair = combo with salmeterol)– Triamcinolone (Azmacort)

• Important to note – Low, intermediate, high dose– dosage form and strengths

Non-Steroid “Controllers”Antiinflammatory

• Mast cell stabilizers(inhaled: MDI or nebs)

– Cromolyn (Intal)– Nedocromil (Tilade)

• Leukotriene modifiers(Oral)

– Lipooxygenase inhibitor: Zileuton (Zyflo) – Receptor blockers: Zafirlukast (Accolate) Montelukast (Singulair)

Long acting bronchodilators• Inhaled beta agonist

– Salmeterol (Serevent MDI and Diskus)

– Formoterol (Foradil Aerolizer)– Night time, exercise or adjunct to

anti-inflammatory drugs• Oral beta adrenergic agonists

– albuterol, metaproterenol, terbutaline

– sustained release for night timeProventil Repetabs, Volmax

– syrups for children (albuterol, metaproterenol

Salmeterol (Serevent) Diskus50 mcg/dose; 60 doses

Open door toreveal mouthpiece

Slide lever. “Click” indicates

dose in place.Dose counter

advances.

Hold level to holdpowder in place.Inhale quickly.

Close door to reset.

Long acting bronchodilators (continued)

• Theophylline– rapid acting, sustained release

(many products recently removed from the market)

– intravenous (aminophylline)– Possibly mild anti-inflammatory– Increased diaphragm contractility

(“diaphragmatic inotrope”)– Primarily reserved for COPD

Other asthma medications

• Oral or injectable steroids– Prednisone, prednisolone,

methylprednisolone– “burst therapy” for rapid decline– Emergency and hospital use

• Methotrexate• Allergy desensitization• Soluble IL-4 receptor (IL4R) to bind

IL-4 and prevent binding of IL-4 to tissue receptors. 3 mg Q week via inhalation

• Olizumab: recombinant monoclonal antibody to IgE 150-300 mg SC Q 2- 4 weeks

Therapeutic goals:Individualize to patient

• Minimal, infrequent episodes– Freedom from symptoms;

Day and night.• Maintain normal activity

including exercise• Maintain best possible

pulmonary function– Consider what is realistic

• Prevent acute episodes– < 3 beta agonist per week– No emergency room visits or

hospitalizations.

Therapeutic goals (cont.)

• Avoid medication adverse effects• Prevent asthma related death• Meet patient/family expectations• Patient/family education:

– symptoms– triggers– metered dose inhaler technique

(have patient demonstrate)– “reliever” vs “controller” drugs– peak flow meter monitoring

(Green, yellow and red zones)

Environmental Control

• Same as for allergic rhinitis• Bedding• Carpets• Stuffed animals• Pets• Avoidance of allergens and

triggers

Step Approach to Classification and Therapy• Mild Intermittent

– PRN bronchodilators• Mild Persistent

– Symptoms 3-6 times/ week– Add antiinflammatory

• Moderate Persistent– Combinations of

antiinflammatories and long acting bronchodilators

• Severe Persistent• Acute exacerbations

Staging:Further Considerations

• Seasonality• Nocturnal symptoms• Exercise induced• Peak flow monitoring• Daily fluctuations• Cough variant• “Wheezy bronchitis” in

children

COPD: Chronic Obstructive Pulmonary Disease

• Any lung condition causing longstanding airflow limitation with impaired expiratory outflow…

• …airflow obstruction due to chronic bronchitis (and/or) emphysema

• Generally progressive, may be accompanied by airway hyperreactivity, and may be partially reversible

• …caused by abnormal inflammatory reaction to chronic inhalation of particles

• 2-10% of US population over age 554th to 5th leading cause of death

Assessing Peak Flow Rate

Pulmonary function:Bronchodilator tone

• Peak expiratory flow rate (PEFR) in liters/ minute

• Forced expiratory volume in one second (FEV1) in liters

• Normal values vary according to sex, age, height– Reported as absolute values or

– Percentage of normal or of personal best

• Establish patient zones– Green = 80-100% of normal

– Yellow = 50-79% of normal

– Red = <50% of normal

Peak Expiratory Flow Rate

• First blast of air exhaled by the patient reaches this flow rate almost immediately.

• The flow rate quickly slows as more air is exhaled.– Less elastic recoil by lung

• Indirect measure of lumen size of large airways and strength of expiratory muscles during maximal effort.

True Zone Peak Flow Meter

Peak Flow Meter

Directions for use of Peak Flow Meter

• “zero the pointer”– Move indicator to bottom of

numbered scale on meter.• Stand upright• Breathe in as deeply and

completely as possible• Close lips around mouthpiece

to form tight seal– Do not put tongue in opening

• Quickly blow out as hard and fast as you can.

• Note reading; repeat 3 times