Latest in Diagnostic and Treatment Options Wendy L.

Wright, MS, APRN, BC, FAANP

Owner - Wright & Associates Family Healthcare Amherst, NH Adjunct Faculty - University of Wyoming Fay W. Whitney School of Nursing Partner Partners in Healthcare Education www.4healtheducation.com

Asthma 2009:

Family Nurse Practitioner

Objectives Upon completion, the participant will be able to: 1. Identify statistics related to incidence/prevalence of asthma 2. Discuss the signs and symptoms of asthma 3. Discuss treatment options for asthma

Asthma

Asthma is... Derived from the Greek word for panting or breathlessness Recurrent airflow obstruction caused by chronic airway inflammation with a superimposed bronchospasm Leads to wheezing, breathlessness and a cough
Guidelines for the Diagnosis and Management of AsthmaUpdate on Selected Topics 2002. NIH, NHLBI. June 2002. NIH publication no. 02-5075.

Prevalence of Asthma
Impacts approximately 21 million individuals in the United States Most common chronic disease of childhood affecting 6 million children Before adolescence, 2 times more common in boys Increasing incidence of this disease 76% increase in the prevalence of asthma within the past decade
Guidelines for the Diagnosis and Management of AsthmaUpdate on Selected Topics 2002. NIH, NHLBI. June 2002. NIH publication no. 02-5075.

Impact of Asthma
Most frequent cause for hospitalization in children (470,000 each year) Emergency room visits and hospitalizations are increasing Most frequent cause of childhood death, particularly amongst certain groups (children, african americans) 4000 - 5,000 people die yearly from asthma Mannino DM, Homa DM, Akinbami LJ, et al. Surveillance for asthma-United States, 1980-1999.
MMWR Surveill Summ. 2002;51:1-13.

Why Is the Death Rate Increasing?

Multifactorial
Asthma is increasing Asthma is more severe Poor management of the disease Poor patient compliance Inadequate patient and provider response to signs of worsening trouble

Misconceptions and Facts

Asthma symptoms can begin at any age Most often misdiagnosed or underdiagnosed in the elderly
Fail to report symptoms because it is thought to be normal Attribute the symptoms to comorbid diseases
Mannino DM, Homa DM, Akinbami LJ, et al. Surveillance for asthma-United States, 1980-1999. MMWR Surveill Summ. 2002;51:1-13.

Misconceptions

Most people think that children will outgrow asthma

Children who suffer from intermittent wheezes have a 50% chance or better of outgrowing this disease Children with persistent wheezing have only a 5% chance of outgrowing this disease
Fuerra S, Wright AL, Morgan WJ, et al. Persistence of asthma symptoms: role of obesity and onset of puberty. Am J Respir Crit Care Med. 2004;170:78-85.

Pathophysiology of Asthma
Genetic predisposition
Chromosome: 5Q31-Q33

Results from repeated exposure to allergens in the individual already equipped with the genetic predisposition Upon exposure to an allergen, there is a release of IgE antibodies IgE antibody binds with the antigen

Pathophysiology of Asthma
IgE/allergen complex - then attaches itself to the mast cells on the nasal and bronchial mucosa Release of numerous chemical mediators

Histamine
Histamine is stored mainly in the mast cell
Circulated in the blood via the basophil

Causes an increase in blood flow to the affected area. Responsible for the increased nasal discharge, edematous mucous membranes, sneezing, itchy nose and eyes, and hives Also associated with airway inflammation and bronchoconstriction

Components of Asthma
Asthma Triggers Allergens Smooth Muscle Dysfunction
Hypertrophy Hyperplasia Inflammatory Mediator Release

Exercise

Irritants

Viruses

Weather

Inflammation
Mucus Secretion Architectural Changes Epithelial Damage

Edema Impaired Ciliary Function

Bronchial Constriction

Bronchial Hyperreactivity

Inflammatory Cell Infiltration

Symptoms Exacerbations
Adapted from Creticos. Adv Stud Med. 2002;2(14):499-503.

Consequences of Inflammation in Asthma

Stimulus
(Antigen, virus, pollutant, occupational agent)

Altered airway physiology Airflow obstruction

Acute Inflammation Resolution

Airway dysfunction

Chronic Inflammation

Injury Repair
Permanently altered lung function Remodeling (fixed changes in the structure of airway)

Asthma: Pathophysiologic Features and Changes in Airway Morphology

Airway lumen narrowing Epithelial damage Airway smoothmuscle hypertrophy, hyperplasia, and bronchoconstriction Inflammatory cell infiltration Mucus hypersecretion Thickening of basement membrane Mucous gland hypertrophy and hyperplasia

Edema

Vascular dilation
Goblet cell hyperplasia

Adapted from Expert Panel Report. Guidelines for the Diagnosis and Management of Asthma. NIH, NHLBI. 1991. NIH publication 91-3042.

Cross Section of Bronchiole Showing Bronchospasm

Color Atlas of Respiratory Disease. Volume 2, 1995.

Epithelial Damage in Asthma

Normal
Jeffery P. In: Asthma, Academic Press 1998.

Asthmatic

Basement Membrane Thickening

Jeffery P. In: Asthma, Academic Press 1998.

Triggers
Inhalant allergens are the most common triggers for both asthma House dust Pollens Mold spores Animal and insect emanations
Cockroach feces

Triggers

Chemicals Perfumes Foods

Sulfites (wine), shrimp, dried fruit, processed potatoes, beer

Viruses or infections Cold air

Triggers

Tobacco smoke Pollution

Work exposures

Exercise

Gastroesophageal Reflux - A Significant Factor in Children

84 healthy infants and children referred for an evaluation of daily wheezing All evaluated for reflux 64% had positive evaluations for reflux After 3 months on anti-reflux treatment, 64.8% of the infants/children were able to discontinue all daily asthma medications (including nebulized flunisolide)
Sheikh S. et. Al. Pediatric Pulmonology. 1999 Sep; 28(3): 181-6

Asthma is...

A disease of:
Inflammation
Primary Process

Hyperresponsiveness Airway bronchoconstriction Excessive mucous production

Diagnosis of Asthma

Diagnosis of Asthma

History and Physical Examination Spirometry is needed to make diagnosis Monitoring:

Peak Flow Meters

Symptoms and Signs of Asthma in Children and Adults

Coughing, particularly at night or after exercise Wheezing Chest tightness SOB Cold that lingers x months

Methods for Measuring Airway Caliber

Maximum PEFR airflow achieved Home

FVC, FEV1 FEF25%-75%

Office/Clinic

Airway Resistance
Clinic/Laboratory

 2008 Fitzgerald Health Education Associates, Inc.

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Asthma Findings

Typically, reversibility of 12% or greater after administration of a bronchodilator aerosol is consistent with asthma.

Conboy-Ellis, Kathleen. Asthma: Pathogenesis and Management. The Nurse Practitioner: November 2006; Vol.31, No. 11. 24 39.

Rate of Decline in FEV1

1.0 0.8

0.6 FEV1/Ht3 (L/m3) 0.4 Normal subjects (n=186) 0.2 Asthma patients (n=66)

0 0 20 40 Age (Yrs.) 60 80

Adapted from Peat. Eur J Respir Dis. 1987;70:171.

Changes With Age in FEV1 According to Smoking and Asthma Status

1.7
1.5 1.3 HeightAdjusted 1.1 FEV1 (liters) 0.9

Male Smokers
No asthma (n=9332) Asthma (n=630)

1.7 1.5 1.3

Male Nonsmokers
No asthma (n=5480) Asthma (n=314)

HeightAdjusted 1.1 FEV1 (liters)

0.9 0.7 0.5 0.3 20 30 40 50 60 Age (yr) 70 80 20 30 40 50 60 70 80 Age (yr)

0.7
0.5 0.3

Lange et al. N Engl J Med. 1998;339:1194-1200.

The Biggest Predictor of Sudden Death from Asthma

History of hospitalization with or without intubation These individuals are at a significant risk for a serious exacerbation again

Asthma Hyperinflation Diaphragm is down to the 11th ribs Most patients with asthma have normal x-rays

Chronic Asthma Changes

Increased AP Lateral diameter The way you know that AP/Lat diameter is increased is by this clear space between the sternum and the ascending aorta Flat diaphragms

Treatment of Asthma

Evolution of Asthma Paradigms

Symptoms

Bronchial Hyperreactivity

Fixed Obstruction

Relieve Symptoms

Prevent Symptoms Prevent Attacks

Prevent Symptoms Prevent Attacks Prevent Remodeling

Environmental Control: A Useful but Often Ignored Step

Dust Mite Avoidance
Bed linens must be laundered 1-2 times/week Maintain humidity at <50% Encase pillows and mattresses Frequent vacuuming Remember: 30 minutes after vacuuming: increased dust mite emanations in the air Individuals with significant asthma should avoid vacuuming or avoid the room for 30 minutes after vacuuming

Environmental Control: A Useful but Often Ignored Step

Pollen Avoidance
Air-conditioning Minimize outdoor exposures during times of highest pollen counts Keep bedroom windows closed Air filters

Environmental Control
Animal Avoidance Keep animals out of the bedroom If the family has a cat, weekly washing of the cat significantly reduces the allergen load May have to remove animals from home Dry clean upholstery and carpets Cover with an air filter any ducts leading into the bedroom

Environmental Control
Mold Avoidance Children/adolescents with allergic rhinitis and/or asthma should not be sleeping in a damp basement Clean moldy surfaces Avoid houseplants Avoid chores that involve damp grass, leaves

Environmental Control

Avoidance of Non-allergic Triggers Strong emotions Smoke: No smoking in house or car Pollution Cold air Odors Exercise

Childhood Asthma Control Can Predict Adult Lung Status

Study of 119 asthmatic children during 1966 and 1969 Ages: 5-14 were evaluated using FEV1 Follow-up performed 17-18 years later and 27-28 years later Children who were well controlled during childhood had the smallest decline in total lung volume during adulthood

How Are We Doing With Treatment?

Study looking at treatment of children over 10 year period showed an increase in the number of prescriptions for beta agonists
4.0% up to 8.1%

However, despite the significant increase in beta agonist prescriptions, there was only a slight increase in anti-inflammatory medications prescribed (even amongst children using 2+ rescue inhalers/month)
0.4% up to 2.4%
Goodman, DC et. Al. Pediatrics 1999 Aug; 104(2) 187-94

Stepwise Approach for Managing Asthma in Patients Aged 12 Years: NAEPP EPR-3 Guidelines
Severe Persistent Mild Persistent Step 2
Preferred: Low-dose inhaled corticosteroid (ICS) Alternative:

Moderate Persistent
Step 3
Preferred: Medium-dose ICS or

Step 6 Step 5 Step 4

Preferred: Medium-dose ICS + LABA Alternative: Medium-dose ICS and either LTRA, theophylline, or zileuton Preferred: High-dose ICS + LABA and omalizumab use can be considered for patients who have allergies. Preferred: High-dose ICS + LABA + oral corticosteroid and consider omalizumab for patients who have allergies

Intermittent

Step 1
Preferred: SABA prn

Low-dose ICS + Mast cell stabilizer LABA (Cromolyn Alternative: nedocromil), Low-dose ICS leukotriene and either receptor antagonist LTRA, (LTRA), theophylline, or or zileuton theophylline

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Step Approach to Therapy

If control is not achieved with therapy, step up the therapy Once control is sustained for a minimum of 3 months, can consider stepping down the therapy Regardless, therapy should be reviewed q 6 months

Major Focus in EPR-3

Controlling asthma is a major focus of the EPR-3 guidelines

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National Heart, Lung and Blood Institute; National Asthma Education and Prevention Program; Expert Panel Report 3: Guidelines for Diagnosis and Management of Asthma, Full Report 2007.

Monitoring Control in Clinical Practice: Asthma Control Test for Patients Aged 12 Years1
Level of Control Based on Composite Score2 20 = Controlled 16-19 = Not Well Controlled 15 = Very Poorly Controlled Regardless of patients self assessment of control in Question 5
1. Asthma Control Test copyright, QualityMetric Incorporated 2002, 2004. All rights reserved. 2. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/epr3/resource.pdf. Accessed February 5, 2007.

Short Acting Inhaled Beta 2 Agonists

Albuterol (Proventil HFA)
90mcg/puff, 200 puffs 2 puffs q 4-6 hours or 2 puffs 15 minutes before exercise Onset: 5 minutes

Short Acting Beta-2 Agonist

Levalbuterol (Xopenex HFA)

1 2 inhalations every 4 6 hours prn

Short-Acting Beta-2 Agonists

Usage of these medications more than 2 times/week is indicative of poor control Regular, scheduled use of these medications is usually not recommended

Long-Acting Controller Medications

Maintenance or Prevention is the Key

Good management is the key to preventing exacerbations and hospitalizations As with any disease, preventing the problem is always better than treating it

Corticosteroids

Most potent and effective antiinflammatory medication currently available

Inhaled Corticosteroids

Examples
Beclomethasone (Beclovent, Vanceril) Budesonide (Pulmicort turbuhaler) Flunisolide (Aerobid) Fluticasone (Flovent) Triamcinolone Acetonide (Azmacort) Mometasone (Asmanex)

Inhaled Corticosteroids
Side effects
Pharyngitis Dysphonia Oral Candidiasis

Precautions
High dosages: Increased systemic absorption leading to HPA axis suppression Not indicated for an acute exacerbation

To Reduce Side Effects of Inhaled Corticosteroids

Administer with spacers or holding chambers Rinse mouth after inhalation Use lowest possible dose to maintain control Children - monitor growth

Schenkel, E. et. al
98 patients randomized to either placebo or mometasone furoate aqueous nasal spray Ages: 3 - 9 years After 1 year, there was no suppression of height in the children using the nasal corticosteroid when compared with the child using placebo
Pediatrics Vol 105 No. 2 February 2000, p. 22

Remember...

Poorly controlled asthma often delays growth In general, children with asthma tend to have longer periods of reduced growth rates prior to puberty

Mast Cell Stabilizers

Cromolyn Sodium (Intal) Indications

Asthma prophylaxis Prevention of bronchoconstriction before exposure to suspected allergen

Best for mild-moderate disease May be the initial choice for children

Mast Cell Stabilizers

Mechanism of Action
Reduces the production of histamine and prevents the release from the mast cell

MDI or Nebulizer Solution

MDI: > 5 years: 2 puffs po qid Nebulizer Solution: >2 years: 1 ampule qid Begin to work within 15 minutes of inhalation but can take up to 2 weeks to become effective

Mast Cell Stabilizer Side effects

Generally well tolerated
Side effects occur in 1:10,000

Cough Wheezing Rash Nausea

Category B

Non-steroidal Inhaled Antiinflammatory Medication

Nedocromil Sodium (Tilade)
Best for mild - moderate disease Works by reducing the production of histamine and by preventing the release from the mast cells MDI: >6 years: 2 sprays qid Nebulizer: >2 years
0.5% solution; 1 ampule qid

Nedocromil Sodium (Tilade)

Side effects
Unpleasant taste

Precautions
Not for an acute exacerbation

Category B

Leukotriene Receptor Antagonists

Cysteinyl leukotriene production in the body has been associated with airway edema, smooth muscle constriction and the inflammatory process These medications block the leukotriene receptors which in turn is able to prevent inflammation and bronchoconstriction

Leukotriene Receptor Antagonists

(Zafirlukast) Accolate 10mg bid for ages 5-11 20mg bid for 12 and older Studied in children as young as 5 Avoid food 1 hour before and 2 hours after taking: Food decreases the bioavailability of Accolate Metabolism: Metabolized through the CY P450 2C9 and 3A4 pathways
Major pathways in the body Numerous other medications use this same pathway

Zafirlukast (Accolate)
Drug/Drug Interactions
Aspirin: Increased zafirlukast levels by 40% Erythromycin: 40% decrease in zafirlukast Theophylline: Postmarketing reports of increased theophylline levels Coumadin: 35% increase in PT/INR

Zafirlukast (Accolate)
Side effects
Headache (12.9%) Dizziness Nausea Churg Strauss syndrome

Pregnancy: B Precautions
Not for an acute exacerbation

Montelukast (Singulair)
(Montelukast) Singulair
4 mg Granules once daily: 12 23 months

4 mg tablet for children 2 - 5 years of age 5mg qhs for ages 6-14 10mg qhs for ages 15 and older

Montelukast (Singulair)
Drug Interactions
Metabolized through CYP2A6 (minor pathway) Phenobarbital: decreases montelukast but no dosage adjustment is required

Side effects: headache, fatigue, dizziness, Churg-Strauss Precautions

Not for an acute exacerbation

Category: B

Methylxanthines
Theophylline
Theo-24, Theo-Dur, Uni-Dur, Slo-Bid Bronchodilates and increases the force with which the diaphragm contracts 6 years and older Difficult to manage and as a result has not really gained wide spread acceptance Indicated for individuals with moderate to severe asthma Numerous drug interactions

Theophylline
Numerous medications, foods and chemicals interact with theophylline
All of the following decrease theophylline levels
Smoking (cigarettes and marijuana) High protein/low carbohydrate diet Phenytoin Phenobarbital Carbamazepine Ketoconazole Diuretics

Theophylline
Theophylline levels (normal 6-15mcg/dL)
15-25: GI upset, N/V, diarrhea, abdominal pain 25-35: Tachycardia, occasional PVCs >35: Ventricular tachycardia, seizures

Category: C

Long Acting Inhaled Beta 2 Agonist Salmeterol (Serevent)

Diskus >4 years of age-1 puff po q 12 hours No role for acute exacerbations Seems to help children affected by the nocturnal cough and wheezing Good for prevention of exercise induced asthma

Long Acting Inhaled Beta 2 Agonist

Foradil Aerolizer
> 5 years of age: 1 inhalation every 12 hours Also may be used for prevention of EIB

Omalizumab (Xolair)
Indicated for adults and adolescents (12 years of age and above) with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen Andwhose symptoms are inadequately controlled with inhaled corticosteroids SC injection

Omalizumab (Xolair)
Recombinant DNA-derived humanized IgG1 monoclonal antibody that selectively binds to human immunoglobulin E (IgE). Inhibits the binding of IgE to the high-affinity IgE receptor on the surface of mast cells and basophils Limits the degree of release of mediators of the allergic response.

Last.

Dont forget to treat the nose 85% of individuals with asthma have concomitant allergic rhinitis

Acute Asthma Exacerbation Management

Acute Asthma Exacerbation

Measure FEV1 Inhaled short acting beta 2 agonist: Up to three treatments of 2-4 puffs by MDI at 20 minute intervals OR a single nebulizer Can repeat x 1 2 provided patient tolerates Prednisone
What dose and schedule??

Management of Moderate Exacerbations: Response from ED Treatment

Good Response Symptom relief sustained x 1hr; FEV1 or PEF 70% D/C home Continue SABA & oral corticosteroid Consider inhaled corticosteroid (ICS) Patient education / asthma action plan
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Management of Moderate Exacerbations: Response from ED Treatment

Incomplete Response Mild-moderate symptoms, FEV1 or PEF 40-69% SABA, oxygen, oral or IV corticosteroids Can D/C home Poor Response Marked symptoms, PEF <40% Repeat SABA immediately ED / 911; oral corticosteroid
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Key Differences in the EPR-3 Report

Point of discharge FEV1 or PEF 70% predicted Response sustained 60 minutes after last treatment Normal physical exam Continued ED treatment needed FEV1 or PEF 40-69% predicted Consider adjunct therapies FEV1 or PEF <40% predicted
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Thank you for your time and attention.

Wendy L. Wright, MS, APRN, BC, FAANP WendyARNP@aol.com