ASTHMA

DEFINITIONChronic inflammatory disorder of the airways

Widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment

Bronchial hyperresponsiveness to a variety of stimuli

affects 300 million people world-widesocio-economic impact is enormous, poor control leads to days lost from school or work, unscheduled health-care visits and hospital admissions

Adult Asthma Facts14.5 million workdays lost due to asthma, a 2.3 fold increase from the early 80s to the mid 90sAdults accounted for over 1.3 million ED visits and 288,000 hospitalizations due to asthmaOne third of asthma related deaths occur in patients 35-44 years oldOver 50% of asthma related deaths occur in patients 65 years and older

Morb Mortal Wkly Rep. 2002 March 29; 51:1-13.

Atopymajor risk factor for asthmagenetically determined production of specific IgE antibodysuffer from other atopic diseases, particularly allergic rhinitis and atopic dermatitis (eczema)most common allergens are - house dust mites, cat and dog fur, cockroaches, grass and tree pollens

Most Patients with Asthma Have Allergic Rhinitis Approximately 80% of asthmatics have allergic rhinitis

Adapted from The Workshop Expert Panel. Management of Allergic Rhinitis and its Impact on Asthma (ARIA) Pocket Guide. A Pocket Guide for Physicians and Nurses. 2001; Bousquet J and the ARIA Workshop Group J Allergy Clin Immunol 2001;108(5):S147-S334; Sibbald B, Rink E Thorax 1991;46:895-901; Leynaert B et al Am J Respir Crit Care Med 2000;162:1391-1396.

Asthmaalone

Allergic rhinitisalone

Allergicrhinitis

+ asthma

IgE and Asthma in Adults

Asthma

Serum IgE (IU/mL)

Od

ds

ra

tio

N = 2657

0.32 1 3.2 10 32 100 320 1000 3200

11

2.52.5

55

1010

2020

4040

Burrows B, et al. New Engl J Med. 1989;320:271-277.

Intrinsic Asthmanegative skin tests to common inhalant allergens and normal serum concentrations of IgElater onset of disease (adult-onset asthma), commonly have concomitant nasal polyps, and may be aspirin-sensitive

THE HYGIENE HYPOTHESIS

AIR POLLUTIONsulfur dioxide, ozone, and diesel particulates, may trigger asthma symptomsIndoor air pollution may be more important with exposure to nitrogen oxides from cooking stoves and exposure to passive cigarette smoke

OCCUPATIONAL EXPOSURE

relatively common and may affect up to 10% of young adultsChemicals such as toluene diisocyanate and trimellitic anhydride, fungal amylase in wheat flour in bakerssuspected when symptoms improve during weekends and holidays

ALLERGEN SENSITIZATION

DENDRITIC CELL WITH AN ALLERGEN

DENDRITIC CELL CAPTURES THE ALLERGEN AND RUNS WITH IT TO THE LYMPH NODE

DENDRITIC CELL RELEASES THE

ALLERGEN

T CELL CAPTURES THE ALLERGEN

CELL RECRUITMENT

MUSCLE CELL HYPERTROPHY

TISSUEDAMAG

E

MORE TISSUE DAMAGE

IgE-dependent Release of Inflammatory Mediators

IgEAllergens

FcεRI

Over MinutesLipid mediators: ProstaglandinsLeukotrienes

WheezingBronchoconstriction

Over HoursCytokine production:Specifically IL-4, IL-13

Mucus productionEosinophil recruitment

Immediate ReleaseGranule contents:Histamine, TNF-α, Proteases, Heparin

Sneezing Nasal congestionItchy, runny noseWatery eyes

Before 10 Minutes After Allergen Challenge

Bronchoconstriction

Mechanisms of Airway Obstruction

Smooth MuscleContraction

MucusHypersecretion

Loss of ElasticRecoil

? PeribronchialFibrosis

Airway WallEdema

Vascular dilatation

Airway Inflammation in Asthma

Acute Fatal Asthma

Impact of Inflammation on Small AirwaysImpact of Inflammation on Small Airways

Normal Chronic Severe Asthma

CLINICAL FEATURES AND

DIAGNOSIS

SYMPTOMSRecurrent episodes of:

Shortness of breathWheezingChest tightnessCough, particularly at night and early in the morning

PATTERN OF SYMPTOMSPerennial, seasonal or both

Continual, episodic or both

Diurnal variations, especially nocturnal and on awakening early in the morning

PRECIPITATING AND/OR AGGRAVATING FACTORS

Viral respiratory infectionsEnvironmental allergensExerciseOccupational chemicals or allergensIrritantsChanges in weatherEndocrine factorsGERDSinusitis

PHYSICAL EXAMNormal physical exam - asthma is under controlExpiratory wheezing with normal or decreased air movementAccessory respiratory muscle useOminous sign- no wheezing with decreased air movement

Cough may be the dominant symptom in some patients, and the lack of wheeze or breathlessness may lead to a delay in reaching the diagnosis of so-called ‘cough-variant asthma

EVALUATION

CLINICAL HISTORYSPIROMETRYMETHACHOLLINE CHALLENGE TESTALLERGY SKIN TESTS

Spirometry: A Simple, Basic Measurement

Essential to initial evaluationHelps assess severity of airflow obstructionAids in differential diagnosis

Obstructive versus restrictive airway diseaseReversibility of airflow obstruction

Confirms periodic home PEFR measurements in selected patients

Spirometry in asthma

reduced FEV1, FEV1/FVC ratio, and PEFImprovement in FEV1>12% with bronchodilator therapy Measurements of PEF twice daily may confirm the diurnal variations in airflow obstruction – more than 20% is considered diagnostic

FlowFlow

(l/s)(l/s)

Volume (l)Volume (l)

-2-2

00

-4-4

11

33

22

44

55

21 3 4 5

-6-6

Pre-albuterolPost-albuterolPredicted

Spirometry: Flow-Volume Loops in Asthma

Bronchoprovocation Challenges

methacholine or histamine challenge calculation of the provocative concentration that reduces FEV1 by 20% (PC20)Measures the increased AHRexercise testing is done to demonstrate the postexercise bronchoconstriction if there is anpredominant history of EIA

Reasons for Performing Bronchoprovocation Challenges in

Clinical Practice

To quantify the severity of the airway hyperresponsiveness(AHR)Clarify a clinical diagnosis of asthma when a reasonable degree of doubt existsTo determine the presence of bronchial hyperresponsiveness in patients with chronic cough

ALLERGIC TRIGGERS

INHALANT ALLERGENS

Animal allergensHouse-dust mites Cockroach allergensIndoor fungi (molds)Outdoor allergens

ALLERGEN SKIN TESTS

Eugene Braunwald, Atlas of Internal Medicine, 2nd edition

EVALUATIONCBC with differential ( eosinophilia often seen in asthma, ABPA and CS vasculitis)Total igEspecific IgE to inhaled allergens [radioallergosorbent test(RAST)]CXRCT of the chestABG in status asthmaticus

Exhaled NO is now being used as a noninvasive test to measure eosinophilic airway inflammationThe typically elevated levels in asthma are reduced by ICS, so this may be a test of compliance with therapy

ASTHMA CLASSIFICATION AND THERAPY

Classification of Asthma Intermittent Asthma Persistent Asthma

MILDsx frequency >2/days per week, not dailyFEV1>80%

MODERATEsx frequency dailyFEV1=60-80%

SEVEREsx frequency throughout the dayFEV1<60%

sx frequency less than 2 times / week sx frequency 2 times / week or more

Goals of Therapy: Asthma Control

■ Minimal or no chronic symptoms day or night■ Minimal or no exacerbations■ No limitations on activities; no school/work

missed■ Maintain (near) normal pulmonary function■ Minimal use of short-acting inhaled beta2-

agonist■ Minimal or no adverse effects from

medications

Avoidance of aggravating factors

particularly important occupational asthmarelevant to atopic patients where removing or reducing exposure to relevant antigens, e.g. a pet animal, may effect improvement

House dust mite exposure may be minimised by replacing carpets with floorboards and using mite impermeable beddingMeasures to reduce fungal exposure and eliminate cockroachesMedications known to precipitate or aggravate asthma should be avoided

Smoking cessation

BRONCHODILATOR THERAPIES

beta2-adrenergic agonists, anticholinergics, and theophyllineShort-acting beta2-agonists (SABAs) such as albuterol and terbutaline – doa 3-6 hrs Long-acting 2-agonists (LABAs) include salmeterol and formoterola doa >12 hours

CONTROLLER THERAPIES

Inhaled Corticosteroids - most effective controllers for asthmaSystemic CorticosteroidsAntileukotrienes - montelukast and zafirlukastCromones - Cromolyn sodium and nedocromil sodiumAnti-IgE -Omalizumab

MANAGEMENT OF CHRONIC ASTHMA

Asthma in pregnancy

ACUTE SEVERE ASTHMA