Sabine Schnyder, MD, PGY-3University of Massachusetts, Pediatrics

Childhood Asthma

Definition of Asthma• Chronic inflammatory disorder of the

airways

• many cells and cellular elements play a role

• Susceptible individuals: recurrent episodes of coughing (esp. at night or early morning), wheezing, breathlessness and/or chest tightness

• Episodes usually associated with airflow obstruction that is often reversible, either spontaneously or with treatment.

From: Guidelines for the Diagnosis and Management of Asthma by The National Heart, Lung, and Blood Institute (NHLBI) Health Information Center (HIC),2007

Inflammation

Airway Hyper-responsiveness

Airway Obstruction

Clinical Symptoms

The Global Asthma Burden• An estimated 300 million people worldwide

suffer from asthma, with 250,000 annual deaths attributed to the disease.1

• Asthma is the most common chronic disease among children worldwide

• Most asthma-related deaths occur in low- and lower-middle income countries.

1) World Health Organization. Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approach, 2007.

From: The global burden of asthma: executive summary of the GINA Dissemination Committee report, 2004

Causes of Asthma IInterplay between:• Host factors (particularly genetics)• Environmental exposures• Exposures occur at a crucial time in the

development of the immune system>Definitive cause of the inflammatory process

leading to asthma has not yet been established !

“ Hygiene Hypothesis”

Causes of Asthma IIEnvironmental factors• Two major factors for development, persistence,

possibly severity of asthma:1.Airborne allergens (especially sensitization/exposure

to house-dust mite) 2.viral respiratory infections (including RSV and

rhinovirus)• Other environmental factors under study:

– tobacco smoke – air pollution (ozone and particular matter) – diet (obesity, low intake of antioxidants and/or

omega-3 fatty acids = the American diet)

PathophysiologyAirflow limitation caused by inflammation :

1. Bronchoconstriction—bronchial SM contraction• response to exposure to a variety of stimuli• Stimuli can be allergens or irritants,exercise,etc.• quickly narrows airways, especially when exhaling2. Airway hyper-responsiveness (“twitchy lungs”):• an exaggerated bronchoconstrictor response 3. Airway edema:• More persistent, progressive inflammation• edema, mucus hypersecretion, inspissated mucous

plugs

Restriction vs Obstruction

Restrictive disease prohibits air from flowing INTO the alveoli by not allowing expansion

Obstructive disease prohibits air from flowing OUT of alveoli, trapping air inthe lungs and overinflating them

smooth musclecontraction upon exhalation

Inflammation of the bronchioli

Parenchymal disease (e.g. fibrosis)

Sequence of an Asthma Attack• Airway epithelium: infectious, noxious and environmental insults> injury caused via influx of proinflammatory cells and cytokines• Viral infections,airborne allergens >biphasic response• IgE-mediated “immediate” response to allergen challenge:

mast cells and basophilsdegranulateBronchospasm& release of pro-inflammatory cytokines, chemokines

• “Late phase” obstruction of air flow = 4 to 12 hrs after exposure• Bronchodilators can relax airway smooth muscle, if administered

during the initial period of bronchospasm• Late phase: increased airway

hyperresponsiveness,inflammation> bronchodilator therapy not as effective > anti-inflammatory medication required

Inflammation: Main Players• Mast cells: distinct role in asthma !

– Stimulated by IgE> pro-inflammatory cytokines > the ball gets rolling…– Also produce leukotrienes and histamine >bronchospasms

• T-helper (Th2) lymphocytes: activated by cytokines– Produce more proinflammatory cytokines > amplification of reaction– activate neutrophils and eosinophils> more inflammation– Stimulate B-cells to produce more IgE> cycle

• Proinflammatory cytokines (IL-4, IL-5,IL-13):– believed to trigger intense inflammation of allergic asthma – activate eospinophils and neutrophils

• Chemokines: – Cytokines for chemotaxis and activation of leukocytes– recruit proinflammatory cells, including Th2 lymphocytes, mast cells,

neutrophils, and eosinophils

Think of ASTHMA when you hear …

1. Wheezing:• high-pitched whistling sounds when exhaling >Lack of wheezing and normal chest examination

do not exclude asthma !2. History of any of the following:• Cough (worse particularly at night)• Recurrent wheeze• Recurrent difficulty in breathing• Recurrent chest tightness

• Exercise• Viral infection• Inhalant allergens (animals with fur/hair, house-

dust mites, mold, pollen)• Irritants (tobacco or wood smoke, airborne

chemicals)• Changes in weather• Strong emotional expression (laughing/crying)• Stress• Menstrual cycles• at night, awakening patient !

… especially if symptoms occur/worsen with:

Clinical EvaluationHistory:• Elicit pattern of symptoms and observed precipitating

factors = asthma triggers• PMHx: include information about risk factors for asthma

(atopy=eczema, seasonal allergies, food allergies), prior exacerbations, treatments used, and their effects

• FHx: positive family history of parental asthma substantially increases risk of asthma in a child

• Assessment of impact of asthma on the child and family Physical exam: often normal !• Look for signs of atopy, such as eczema or allergic rhinitis >

strongly associated with asthma

Diagnosis of Asthma

• Asthma is essentially a clinical diagnosis !Key elements for diagnosis are: • symptoms of recurrent episodes of airflow

obstruction or airway hyper-responsiveness• airflow obstruction at least partially reversible • alternative diagnoses excluded• Spirometry for definite diagnosis = gold

standard (but often only done if unsure)

Spirometry• 2007 Guidelines recommend objective measurement of

pulmonary function (spirometry) as part of initial evaluation.

• Most children> 6 or 7 years are capable of performing a forced expiratory maneuver, if coached by an experienced technician

• Some centers can test children as young as 5 years of age

• Spirometry should be performed before and after administration of a short-acting bronchodilator

• Spirometry results may be normal, esp. in children with mild asthma.

• FEV1 that increases by 12% or more following the administration of bronchodilators indicates reversible airway obstruction, even if baseline FEV1 is normal.

Normal Spirometry :FEV1/FVC > 85 % (80%)

Lung Function Abnormalities Spirometry (in clinic)Airflow limitation• Low FEV1 (relative to percentage of predicted norms)• FEV1/FVC ratio <0.80Bronchodilator response (to inhaled β-agonist)• Improvement in FEV1 ≥12% or ≥200 mL[*]

Exercise challenge• Worsening in FEV1 ≥15%[*]

Daily peak flow or FEV 1 monitoring: • day to day and/or AM-to-PM variation ≥20%[*]

FEV1, forced expiratory volume in 1 sec; FVC, forced vital capacity.

*Main criteria consistent with asthma.

Radiographic Studies I

Chest radiographs (pa and lateral) in children with asthma often appear to be normal, aside from hyperinflation (flattening of the diaphragms) and peribronchial thickening

Radiographic studies IICXR may helpful for1. identifying abnormalities that are hallmarks of

asthma masqueraders:• aspiration pneumonitis• hyperlucent lung fields in bronchiolitis obliterans2. Identify complications during acute asthma

exacerbations:• Atelectasis• Pneumomediastinum• Pneumothorax

Differential Diagnosis I!! Differential diagnosis of asthma is broad !!Upper airway disease: allergic rhinitis or sinusitis –can cause recurrent coughing, particularly at night– often other signs/symptoms to help distinguish it from asthmaExtrinsic or intrinsic obstruction of large airways: –Tracheomalacia, vascular ring, mass, or foreign body–Consider especially if change in airway symptoms with position or failure of symptoms to respond to usual asthma treatment,–foreign body: often history of acute onset of symptoms following a choking episode (more difficult to elicit in small kids)Recurrent aspiration or gastroesophageal reflux :–can result in recurrent bouts of coughing, other respiratory sx–Take careful history of pattern of symptoms !–look for evidence of risk factors for reflux or aspiration, such as prematurity, feeding difficulties, or neurologic impairment

DDX II : Other Obstructive Diseases

• Obstruction of small airways may result in wheezing or other symptoms similar to those found in asthma:– Bronchiolitis– Cystic Fibrosis– Congestive Heart Failure – Chronic Lung Disease of Prematurity

• Recurrent episodes of bronchiolitis in young children are sometimes difficult to distinguish from asthma

• Detailed PMH and careful PE often help to distinguish the latter three conditions from asthma

Vocal cord dysfunction (VCD)

• Presents with wheezing or breathlessness associated with paradoxic vocal cord adduction during inspiration

• may be difficult to distinguish clinically from asthma• distinct diagnosis, but may also coexist with asthma• more common in adolescents and young adults• does not respond to asthma medications• include in DDX of atypical/difficult-to-control asthma• diagnosis may be suspected based on clinical history and

spirometry that shows a flattened inspiratory loop• Definitive diagnosis usually made by a specialist and based on

viewing of vocal cords during an episode

Four main Components of Asthma Managements (NIH guidelines)

1. REGULAR ASSESSMENT AND MONITORING

Asthma checkups:• Every 2–4 wk until good control is achieved• 2–4 per yr to maintain good control• Lung function monitoring

2. CONTROL OF FACTORS CONTRIBUTING TO ASTHMA SEVERITIY

• Eliminate or reduce problematic environmental exposures• Treat co-morbid conditions: rhinitis, sinusitis, gastroesophageal reflux

3. ASTHMA PHARMACOTHERAPY• Long-term-control vs quick-relief medications• Classification of asthma severity for anti-inflammatory pharmacotherapy• Step-up, step-down approach• Asthma exacerbation management

4. PATIENT EDUCATION

Provide a two-part care plan :• Daily management• Action plan for asthma exacerbations

Pharmacotherapy for AsthmaTwo main broad classes of drugs:1. Bronchodilators=> bronchospasm• Beta agonists, fast-acting vs long

acting (SABA vs LABA)• Others: epinephrine, theophyllins2. Steroids => inflammation, edema• Oral/IV = systemic vs• Inhaled = local

Third group : Leukotriene modulators => mast cells (atopy), immune system; eg. LTRA = leukotriene receptor antagonists)

How to decide what therapy to use• determine degree of severity• best to do at time of diagnosis, before initiation of

therapy• 4 categories of asthma severity:

– 1-intermittent– 2-mild persistent– 3-moderate persistent – 4-severe persistent

• Most important distinction between intermittent & persistent:

=> kids with persistent asthma >start on long-term control meds !!

Severity Days and Nights with Symptoms

Interference with normal activity

Pulmonary Function

Exacerbations

Severe persistent0-4 years

All day > 1 n/week

Extremely limited

N/A (See mild persistent)

5-11 years All dayMost nights

“ FEV1 < 60%FEV1/FVC<75%

≥ 2 / year

Moderatepersistent0-4 years

Daily2-4n/month

Some limitation

N/A (See mild persistent)

5-11 years Daily> 1 n/week

“ FEV1 60-80%FEV1/FVC:75%-80%

≥ 2 / year

Mild persistent0-4 years

3-6 d/week1-2 n/month

Minor limitation

N/A ≥ 2 / 6 monthsOR ≥ 4 episodesof wheeze/year + asthma RF

5-11 years 3-6 d/week3-4 n/month

“ FEV1 > 80%FEV1/FVC >80%

≥ 2 / year

Intermittent0-4 years

≤ 2d/week0 n/month

None N/A 0 – 1 / year

5-11 years ≤ 2d/week≤ 2 n/month

“ FEV1 >80%FEV1/FVC >85%

0 – 1 / year

Bronchodilators I: the Beta-agonists

Short-acting β-agonists(SABA): Albuterol / Salbutamol•Act on beta2 receptors of the adrenergic systemTherapeutic actions: Main benefit = relax airway smooth muscle

–reduced vascular permeability and edema –improve mucociliary clearance

•Rapid onset of action, 4–6 hr duration of action, very effective •1st drug of choice for acute asthma symptoms (“rescue” meds)•CAVE: Overuse a/w increased risk of death/near-death episodes !Main side effects:

–palpitations, tachycardia, arrhythmias, tremor–Hypoxemia > V/Q mismatch, when giving continuously– also shifts potassium intracellularly

•Preferred route is inhaled, less systemic side effects•Salbutamol can be given orally if inhalation device not available> Syrup or tablet

Bronchodilators IILong-acting beta agonists (LABA): salmeterol, formoterol • β-agonists, but used as controller meds, not intended for “rescue” • prolonged duration of effect of at least 12 hr• nocturnal asthma, frequent SABA use for exercise-induced sx • Major role is “add-on” in pts suboptimally controlled on ICS txAnticholinergics: ipratropium bromide, much less potent than SABA• Primarily used in treatment of acute severe asthma • When used with a SABA, can improve lung function, reduce rate of

hospitalization in children who present to ER with acute asthma• Few to no central nervous system side effectsEpinephrine: IM/IV, INH: acts on all adrenergic receptors• fast onset, but also non-specific and short-lived action; CAVE rebound Aminophylline: increase cAMP by unknown mechanism• IV/PO; CAVE seizures, arrhythmias, hypotension, shock • => CR monitor !! and check levels if possible…

Corticosteroids I: systemicAction: • Anti-inflammatory > reduce edema, irritation; “Immunosuppression”• Onset of action: appr. 4-6 hrs !! > give immediately if acute !!• Short course> faster recovery, less recurrence• Either single doses in ED or short courses orally in clinic setting• both oral/IV in hospitalized children [depending if taking PO]>Depo-Medrol (IM), Solu-Medrol (IV) “Burst” : 1–2 mg/kg/day qd>Prednisone/Prednisolone: 1–2 mg/kg/day bid (max: 60 mg/d)

Side effects: • Behavioral: ‘hyperactivity’, cranky child, polyphagia; rarely : psychosis !• transient leukocytosis, hyperglycemia, hypertension• Long term/chronic: stunted growth, osteoporosis, full blown Cushing’s ONLY USE FOR ACUTE EXACERBATIONS ! If > 3 times/y >re-evaluate! If exposed to chickenpox or measles, consider passive Ig prophylaxis Risk of complications with herpes simplex and tuberculosis !

Corticosteroids II: Inhaled• NAEPP: daily ICS therapy for patients with persistent asthma • reduce asthma symptoms, improve lung function, reduce AHR,

reduce “rescue” medication use • Reduce ER visits, hospitalizations, prednisone use for

exacerbations by 50% !• ICSs are available in MDIs, DPIs, or in suspension for nebs• Fluticasone propionate, budesonide => “2nd-generation” ICS >

increased anti-inflammatory potency, reduced systemic bioavailability= less side effects

• Initial dose is based on the determination of disease severity• Fraction of initial dose often sufficient to maintain good control• Widely used in adults, use in children has lagged > concerns of

potential for adverse effects with chronic use• Clinically significant adverse effects typically not seen in

children on ICSs in recommended doses

Acute asthma management• Initial presentation or exacerbation of existing asthma• If severe : Status Asthmaticus > EMERGENCY !• Important to recognize degree of airway obstruction;

watch for – Tachypnea– unable to speak in full sentences– Flaring, retracting, grunting, tripoding– ‘Tight’ breath sounds => poor air movement– Patient may NOT wheeze if severely obstructed– O2 Saturation may remain normal until shortly before

respiratory failure ! > don’t be falsely reassured !

WHO guidelines I (Pocketbook)➤ 1st episode of wheezing and no respiratory distress:

manage at home with supportive care only, bronchodilator is not necessary ➤ If in respiratory distress or recurrent wheezing: give inhaled salbutamol by nebulizer or MDI– If not available, give SQ epinephrine instead

➤ Reassess after 30 minutes :— If respiratory distress resolved: advise mother on home care with inhaled (preferred) or oral salbutamol— If respiratory distress persist: admit to hospital and treat with oxygen, rapid-acting bronchodilators et al. ➤ If central cyanosis or inability to drink, give oxygen, rapid-acting bronchodilators et. al immediately

WHO guidelines II (pocketbook) ➤ If admitted, give oxygen, a rapid-acting bronchodilator (RABD), 1st dose of steroids promptly

➤ If no response in 15 min: rapid-acting bronchodilator up to Q1hr ➤ If no response after 3 doses, add IV aminophylline

Try to avoid intubation !!!

Supportive care while inpatient: ➤ daily maintenance fluids appropriate for age/size

➤Encourage breastfeeding and oral fluids ➤Encourage adequate complementary feeding in young child as

soon as food can be taken

Discharge Criteria (ideal world):> Medical Stability:• sustained improvement in symptoms, normal PE• bronchodilator treatments at least 3 hrs apart• PEF > 70% of predicted or personal best• oxygen saturation > 92% on room air> Home Supervision: • Capability to administer intervention, observe,

respond to clinical deterioration ! • Asthma Education !> Oral bronchodilators upon d/c per WHO pocketbook:• inhaled salbutamol if available /affordable• If not: oral salbutamol (syrup or tablets) Q 6–8 hrsPRN

Long-term managment• Use step-wise approach for long-term management • Base management on severity as well as level of

asthma control (known asthmatics)• FREQUENT follow-up is key ! > Reassessment !• Each patient should have an asthma action plan at

home with instructions on:– What to watch out for in terms of symptoms– What immediate action to take (E.g, rescue inhaler)– When to call a doctor– When to go to the hospital immediately

• Goal is to keep patients OUT of hospital !

Age Step1

Step2

Step3

Step4

Step5

Step6

0 to 4 y SABA

PRNLow-doseICS

Medium-Dose ICS

Med.-Dose ICS+ LABA OR Monte -leukast

High-Dose ICS+ LABA OR Monte-Leukast

High-Dose ICS+ OCS +

LABA OR Monte-leukast

5 to 11y SABA

PRNLow-doseICS

Low-dose ICS + either LABA,

LTRA or theophyllin OR Med.-dose ICS

Med.-Dose ICS+ LABA

High-Dose ICS+ LABA

High-Dose ICS+ LABA

+ OCS12 y toadult

SABAPRN

Low-doseICS

Low-dose ICS + LABA

OR Medium- dose ICS

Med.-Dose ICS+ LABA

High-Dose ICS+ LABA

High-Dose ICS+ LABA

+ OCS

Take home messages• Hallmarks of asthma are inflammation and airway

hyperresponsiveness/bronchospasm• Identify triggers and counsel families on how to avoid • SABA should be used as rescue medication only !• If a patient has persistent asthma, they should be on

maintenance treatment – start with ICS, step-wise approach depending on resources you have

• Maintain frequent follow-up to assure good control• For acute exacerbations, use fast acting bronchodilators

and start systemic steroids asap ! • Education, education, education !

QUESTIONS ?