Tips for Caring for Tips for Caring for Patients with Reactive Patients with Reactive

AirwaysAirways

Jason E. Knuffman, MDJason E. Knuffman, MD

AllergyAllergy

October 27, 2004October 27, 2004

Objectives for CMEObjectives for CME

• Review the goals of asthma care

• Review the fundamental therapeutic options for asthmatics

• Recognize allergic asthmatic patients who would potentially benefit from referral to a specialist

• This talk has not been sponsored by any organization

OutlineOutline

• Impact of Asthma

• Goals of Therapy

• Conventional Treatment of Asthma

• Allergic Asthma

• Referral Indications

Impact of AsthmaImpact of Asthma

• 15 million persons with asthma in U.S.

• 4.8 million children – most common chronic disease of childhood

• 478,000 hospitalizations and 4,400 deaths per year– A disproportionate rate among African

American and Hispanic populations

Middleton

GoalsGoals

• Identify asthma triggers• Correct inhaler or device technique• Focus on long-term control of symptoms• Maintaining normal daily activities, including

exercise• Minimize ER or urgent care visits• No medication side effects• Recognize signs of impending exacerbation and

execute action plan• Education

Middleton

Conventional therapyConventional therapy

• Environmental control– Need to identify what patient is allergic to by

skin or serum testing– Identify respiratory irritants (cigarette smoke,

pollutants, perfumes etc.)– Aspirin sensitivity – Vigorous attempts at smoking cessation are

considered first-line therapy equivalent!!!

Middleton

Environmental Control cont…Environmental Control cont…

• House dust mite (HDM) measures– Removal of carpet, upholstered furniture– Mattress and pillow encasements (~$100)– Routine hot-water washing of bedding– Humidity <50%– Less useful options are HEPA filters and other air

filters (not recommended)

• For pets, avoidance is key– Periodic exposure exception

Middleton

PharmacotherapyPharmacotherapy

• Two key goals of therapy:– Reduce airway inflammation– Improve symptom control

NAEPP

NAEPP

Controller MedicationsController Medications

• Daily usage:– Inhaled Corticosteroids– Long acting ß-2 agonists– Methylxanthines– Mast Cell Stabilizers– Leukotriene Modifiers

PharmacotherapyPharmacotherapy

• Inhaled Corticosteroids (ICS)– Drugs of choice for management of persistent asthma– Strong data from randomized, double-blinded,

placebo controlled trials in children and adults supports their efficacy

– Compared to short-acting ß2 agonists¹ alone without a controller med

• Improvements in pre-bronchodilator FEV1• Reduced airway responsiveness• Reduced symptom scores and frequency• Fewer courses of oral corticosteroids (OCS)• Lower hospitalization rates

¹ Childhood Asthma Management Program trial et al from 2002 update

Comparing ICS to other Comparing ICS to other controllerscontrollers

• Long acting ß agonists vs. ICS– ¹Those using salmeterol as monotherapy had

deterioration in FEV1 over time

• Theophylline vs. ICS– ²ICS reduced symtoms,supplemental

bronchodilators, OCS needs, bronchial hyperresponsiveness and eosinophilia

– No outcomes were improved with theophylline– May get small steroid-sparing effect

¹Verberne et al.1997; ²Reed et al 1998

Comparing ICS to other Comparing ICS to other ControllersControllers

• Nedocromil– ¹CAMP trial found no difference between

nedocromil and placebo in:• Lung function• Symptom scores

– Nedocromil DID reduce use of OCS and reduced number of urgent care visits over placebo

– Results strongly favored ICS over nedocromil when they were compared on all endpoints

¹CAMP data

PharmacotherapyPharmacotherapy

• Leukotriene Modifiers– 5-lipoxygenase inhibitors (zileuton-discontinued)– Leukotriene receptor antagonists (zafirlukast and

montelukast)– Add-on therapy to ICS– If used as monotherapy, there has been shown to be

modest improvement in lung function in adults and children compared to placebo

– Again, ¹ICS significantly and clearly favored over LTRA’s in persistent asthma

¹Busse et al, 2001

PharmacotherapyPharmacotherapy

• Mast Cell Stabilizers – Nedocromil and cromolyn– Used for preventative purposes only– Could be considered for treatment of

persistent asthma– NOT preferred, though

PharmacotherapyPharmacotherapy

• Long Acting ß agonists– ¹164 patients ages 12-65 with well controlled asthma

on ICS • Randomized to continued ICS vs. LABA• 16 week study• LABA group had more treatment failures (24% vs. 6%)• LABA group with more exacerbations (20% vs 7%)

– Evidence supports steroid-sparing effect– Can be useful for exercise-induced bronchospasm

¹Lazarus et al 2001

Rescue MedicationsRescue Medications

• As-needed usage:– Short acting ß agonists– Oral corticosteroids

PharmacotherapyPharmacotherapy

• Short-acting bronchodilators– Numerous tradenames

• Albuterol, pirbuterol

– Drug of choice for “rescue”purposes– NOT for scheduled usage– Usage reflects control– Can be used as monotherapy in exercise-

induced asthma

PharmacotherapyPharmacotherapy

• Oral Glucocorticoids– The most potent treatment for asthma

symptoms• Decrease inflammatory cell function and activation• Stabilize vascular leakage• Decrease mucus production• Increase B-adrenergic response

– Work by binding intracellular glucocorticoid receptors and inhibiting transcription of target genes

Middleton

Oral Glucocorticoids, cont…Oral Glucocorticoids, cont…

• Can be used as a ‘short burst’ to win back control of asthma symptoms– ie, prednisone 10mg bid-tid for 5-7 days, then

stop – warn of usual SE’s (increased appetite, sporadic glucose readings, psychiatric etc…)

• Consider methylprednisolone usage if psychiatric SE’s are a concern

– Keep prednisone ‘burst supply’ at home – a good idea with compliant patients

NAEPP

Miscellaneous TopicsMiscellaneous Topics

• Exercise-induced bronchospasm

• Severe, life-threatening asthma

• PREGNANCY…

Asthma in PregnancyAsthma in Pregnancy

• New guidelines are forthcoming – November 2004

• nhlbiinfo@nhlbi.nih.gov

• http://www.nhlbi.nih.gov/about/naepp/

• National Asthma Education and Prevention Program

Allergic AsthmaAllergic Asthma

• Allergen immunotherapy

• Anti-IgE therapy

Allergen ITAllergen IT

• Immunotherapy for allergic rhinitis has clearly proven useful

• IT for asthma demands more carefully selected candidates, and in correct setting is also very effective

• IT is a long-term commitment for the patient– Weekly buildup, initially– Monthly maintenance thereafter– Usually continue shots for 3-5 years

Middleton

Allergen ITAllergen IT

• ¹No new randomized, controlled trials for IT literature in adult asthmatics over last 5 years

• ²Cochrane Airways Group selected RC trials using allergen-specific IT to treat asthma– 75 trials, 3,506 participants– Various antigens used– There was observed an overall significant reduction in

asthma symptoms and medication usage as well as improvement in bronchial hyperreactivity with IT

• NNT=4 to prevent 1 patient with worsening symptoms• NNT=5 to prevent 1 patient from requiring increased meds

¹Norman 2004 ²Abramson 2003

²Abramson 2003Abramson 2003

Abramson 2003

Anti IgEAnti IgE

OmalizumabOmalizumab

Busse and Lemanske 2003

Anti-IgE TherapyAnti-IgE Therapy

• Omalizumab (Xolair)– Approved in 2003 for moderate to severe

asthma– Monoclonal antibody, binds IgE– Shown to reduce asthma exacerbations – Reduces need for oral CSs and reduces dose

of ICSs

Rambasek et al 2004

Omalizumab, cont…Omalizumab, cont…

• Indications:– Perennial allergic asthma (positive skin

testing perennial allergens such as dust mites, cats, dogs, cockroaches)

– IgE level between 30 and 700 IU/ml.– 12 yo and older

Rambasek et al 2004

Omalizumab cont…Omalizumab cont…

• Busse et al, RPCDB trial– 525 patients with severe allergic asthma,

poorly controlled, requiring daily ICS– placebo or omalizumab– kept constant dose of ICS for 16 weeks, then

12 week taper– primary outcome: # of asthma exacerbations– secondary outcome: mean reduction of ICS

dose

Busse et al. JACI 2001; 108: 184-90.

Busse et alBusse et al

Busse et alBusse et al

Busse et al

Busse et al

Omalizumab, cont…Omalizumab, cont…

• Administration:– Dosed by formula incorporating body weight

and IgE level– Subcutaneously, every 2-4 weeks depending

on the dose– Need to monitor in office for urticaria (2-3%)

or anaphylaxis (0.01-0.1%)– Average cost between $5,000 and $25,000

per year

Rambasek et al 2004

Referral IndicationsReferral Indications

• Is it asthma?

• Allergic component

• Significant morbidity, altered lifestyle

• Steroid-dependent

• Overuse of beta agonists

• Education

ConclusionConclusion

• Impact of Asthma

• Goals of Therapy

• Conventional Treatment of Asthma

• Allergic Asthma

• Referral Indications

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