ASTHMA

Adapted from source

 Epidemiology in Australia
• Prevalence in adults: 10 – 12%
(England: 15.3%, Germany: 6.9%)
• Prevalence in children: 14 – 16%
• More common in women and indigenous
Australians
• 1.7% of all ED presentations, 0.3% of all deaths,
0.6% of hospital admissions, 2.5% of GP
encounters
• 40% of children with asthma live with smokers
 Etiology
Atopy is largest risk factor for development of
asthma (increased IgE production)
Suspect atopy if there is history or family history of
allergic rhinitis, urticaria, eczema, positive prick test,
increased levels of IgE, positive reaction to specific
provocation test.
Pevalence of atopy > 30%, not all atopic people
develop symptoms

• Allergic asthma: atopic component, earlier onset

(30%)
• Nonatopic, idiosyncratic asthma: No atopic
characteristics, later onset (> 40 yrs.) – 30%
• Mixed etiology asthma – 40%
 Etiology
• Genetic predisposition.
If both parents have allergic asthma,
children have a risk of 60 – 80 % of
developing it. If one parent has allergic
asthma, risk is 30 – 40%
25% of patients with allergic rhinitis due to
pollen will develop allergic asthma within
10 years.
 Pathogenesis
Persistent subacute inflammation of
airways

mucous membranes oedematous,

infiltrated with eosinophils, neutrophils and
lymphocytes, elevated capillary density,
glandular hypertrophy and denudation of
epithelium
 3 Characteristics
• Airway inflammation (allergens or infection),
involvement of mast cells, T lymphocytes,
eosinophils, and mediators of inflammation
(histamin, eosinophil chemotactic factor of
anaphylaxis, leucotriens, bradykinin)
• Bronchial hyperreactivity (prevalence 15%, but
only 5% have asthma)
• Endobronchial obstruction through
bronchospasm, oedema of mucous membranes
and inflammatory infiltration, large amounts of
thick mucous secretions, airway remodelling
 Cellular sources of inflammatory mediators and
effects
Cells Mediators Effects
Mast cells Histamine Bronchoconstriction
Macrophages Leukotriens Plasma exudation
Prostaglandins Mucus hypersecretion
Eosinophils
Thromboxane Structural changes
T Lyphocytes Bradykinin (fibrosis, hyperplasia,
Epithelial cells Tachykinins angiogenesis, mucous
Adenosine hyperplasia)
Fibroblasts
Neurons Anaphylaxotoxins
Endothelins
Neutrophils
Nitric Oxide
(Platelets, Cytokines
Basophils?) Growth factors
PAF
 Categories of Asthma
• Allergic
• Pharmacologic
• Environmental
• Occupational
• Infectious
• Exercise induced
• Asthma because of gastrooesophageal
reflux
 Allergic
• Controlled by Th2 cells and B cells (IgE
production)
• Interaction of antigen with mast cell-bound
IgE, leading to mast cell degranulation and
recruitment of inflammatory cells in the
bronchial mucosa
• Early reaction – immediate
bronchoconstriction, IgE mediated
• Late reaction, IgG mediated,
bronchoconstriction in 30- 50% of patients
after 6 – 10 hrs
 Pharmacologic
• Aspirin and NSAID ~ 10% of asthmatics
(mast cell activation through chronic
oversecretion of cysteinyl leukotrienes, not
IgE mediated, leukotrien antagonists
inhibit reaction)
• Beta blockers (contraindicated in Asthma)
• Sulfur agents, tyramine, glutamate
(sanitizing and preserving agents in food,
beverages, drugs, inhalers), mechanism
unknown
 Environmental
Asthma through climatic conditions that
promote concentration of atmospheric
pollutants or antigens
Smog, mostly in densely populated and
industrialised areas
Pollutants are ozone, nitrogen, nitrogen
dioxide, sulfur dioxide
Greater effects during periods of high
ventilation
 Occupational asthma
• High mulecular compounds (IgE mediated)
wood and vegetable dusts, pharmaceutical
agents, biologic enzymes, animal and
insect dusts, latex, fish and seafood
• Low molecular compounds (direct mast
cell degranulation)
metal salts, industrial chemicals and
plastics, formaldehyde, persulfates,
isocyanates
 Infectious exacerbated asthma
• Viral respiratory infections
Upper respiratory tract infections are the most
common trigger for exacerbation of allergic
asthma.
RS virus, Influenza- and Parainfluenza virus,
Rhinovirus
long lasting infection necessary to destabilise
preexisting asthma, T cell derived cytokines
attract inflammatory cells into airway mucous
membranes
 Exercise induced
• After exertion, not during exertion
? thermally induced hyperaemia and
capillary leakage in airway wall
High ventilation of cold air causes more
severe response
Does not cause airway hyperreactivity or
long term sequelae
 Pathophysiology
• Reduction in airway diameter
contraction of smooth muscle, vascular
congestion, oedema of bronchial wall, large
amounts of thick mucous secretions
• Increase in airway resistance, decreased flow
rates, hyperinflation, increased work of
breathing, mismatch of ventilation and perfusion
• When patient presents for therapy, FEV1 is
usually < 40% of predicted
• Histologically hypertrophy of smooth muscles,
hyperplasia of vessels, mucosal oedema,
denudation of epithelium, thickening of basal
membrane, eosinophilic infiltrates, airway
remodelling
 Clinical features during attack
• Dynpnoea, cough and wheezing
• Prolonged expiration, tachypnoea, mild
hypertension
• Use of accessory respiratory muscles,
hyperinflation, silent lung, pulsus paradoxus
• Curschman‘s spirals, Charcot Leyden crystals
and eosinophils in sputum
• Atelectasis due to mucous plugs, pneumothorax
• Blood gas analysis necessary to diagnose
impending respiratory failure (CO2 retention)
Curschman‘s Spirals
twisted plugs of mucous
 Charcot-Leyden Crystals
Eosinophilic needle-shaped crystalline structures
representing breakdown products of eosinophils.
 Symptoms in mild asthma
• Nocturnal awakening with dyspnoea or
wheezes
• Chronic cough
• Mild episodes of dypnoea
 Diagnosis
• Reversible airways obstruction (FEV1 increases
by a minimum of 12% (15%) after inhalation of a
beta agonist)
• Unspecific bronchial challenge (Histamin,
Metacholin, direct challenge, hypertonic saline,
Mannitol, indirect challenge) shows reduction of
the FEV1 by a minimum of 20% (off steroids for
96 hrs, off antihistamines for 48 hrs, off
theophylline, inhaled beta agonists or
anticholinergics for 12 hours). Direct challenge
more sensitive, indirect challenge more specific.
• Peak flow fluctuations during the day of a
minimum of 20% in a minimum of 3 days a week
for 2 weeks
• Sputum eosinophilia
 Diagnosis
• History! Work history, contact with
animals, onset of symptoms, family
history,
• Total IgE
• Skin prick test
• Specific IgE in serum (less sensitive than
prick test, but very specific)
 Treatment
• Quick relief (inhibition of smooth muscle contraction)
Adrenergic stimulants (inhalative, iv, oral, Salbutamol, )
Theophylline
Anticholinergics (Ipatropiumbromide, Atrovent)
• Long term controller medication
Glucocorticoids (oral, iv, inhaled, Budesonide,
Beclomethasone, Fluticasone), improve sensitivity of beta
receptors
Combined inhaled glucocorticoid and long acting beta
agonist (Serevent, Symbicort)
Leukotrien modifiers (oral, Montelukast, Zafirlukast)
Mast cell stabilising agents (inhaled, Cromolyn, Nedocromil)
– no evidence
Anti IgE Antibody (s.c. Omalizumab, Xolair)
Cyclosporin A, Methotrexate
Best strategy for management of acute
exacerbation of asthma is early
recognition and intervention, before
attacks become severe and potentially life
threatening.
Detailed investigations into the
circumstances surrounding fatal asthma
have often revealed failures of patients
and clinicians to recognize the severity of
disease and to intensify treatment.
 Acute exacerbation, home treatment,
asthma management plan (peak flow falls
by more than 20% of baseline)

• Inhaled or nebulised beta agonists immediately and

20 minutes later. If peak flow increases to > 80% of
baseline, no need for admission. Continue beta
agonists, quadruple inhaled steroid dose or add oral
steroids.
• Peak flow post betaagonists > 50%<80%: oral
steroids
• Patients should present to ED if symptoms do not
improve or if peak flow < 50 % of baseline
• Peak flow > 200 l/min: severe obstruction
 Treatment of acute attack
• Inhaled betaagonist (Salbutamol), in status
asthmaticus often temporary decreased
sensitivity of beta receptors! 6 doses through
MDI (metered dose inhaler) roughly equal one
nebuliser. Repeat 2 after 20 and 40 minutes,
then every 1 to 4 hours.
• Inhaled ipatropiumbromide (Atrovent)
• Oxygen supplementation
• Intravenous Hydrocortisone (antiinflammatory,
antiallergic, immunosuppressiv, improves
sensitivity of beta receptors). Massive dose has
no advantage over large dose (60 – 125 mg of
methylprednisolone)
 Treatment of acute ctd.
• Continous intravenous Aminophylline alone or
combined with betaagonist (Terbutaline) in
status asthmaticus, additive effect to beta
agonists
• Magnesium Sulfate iv (2g over 20 min) ?
Inhibition of calcium influx into airway smooth
muscle cells.
• ABGs necessary to monitor treatment
• If peak flow > 25% of normal, hypercapnia is
unlikely
• Antibiotics in most cases not necessary
 Criteria for hospital admission
• FEV1 or Peak Flow < 40% - 50% of best value
• FEV1 or Peak Flow > 70% of best value do not
need admission
• FEV1 or Peak Flow between 40 and 70% of best
value should be admitted if
 new onset asthma
 multiple prior hospitalizations for asthma
 use of oral corticosteroids at the time of presentation
with acute deterioration
 complicating psychosocial difficulties.
 Risk of fatal asthma
 Risk of fatal asthma
• Previous near fatal asthma
• Admission for asthma during last 12
months
• On 3 or more classes of asthma
medication
• Heavy use of beta agonists
• Repeated ED presentations during the last
12 months
• Brittle asthma
 Brittle Asthma
• Type 1
Patients who consistently demonstrate wide peak flow variation
(greater than 40% diurnal variation for at least 50% of days),
despite maximal medical therapy including at least 1500 µg/day
of inhaled beclomethasone or equivalent, are classified as
having type 1 brittle asthma.
These patients are typically female and aged between 15 and
55 years.
• Type 2
Patients with type 2 brittle asthma appear to be well controlled
between attacks which are often sudden in onset (occurring
within minutes) and are associated with loss of or disturbed
consciousness on at least one occasion.
Severe respiratory acidosis develops quickly in an attack and, if
ventilated, needs support for relatively short time periods.
Equally prevalent in men and women.
 Brittle asthma
• 90% of patients have atopy
• 60 % have food intolerance worsening
asthma (dairy products, wheat, fish, citrus,
egg, potato, soya, peanut, yeast)
• Psychosocial complications common
 Prevention
• Avoidance of exposure to allergen
removal of pets, air filtration devices, travel to
non pollinating areas during the critical times,
control of dust mites by use of plastic lined
covers for mattresses, pillows and comforters,
elimination of carpets and drapes, control of
mould by eliminating plants and keeping the
house dry, in extreme cases change of house,
eliminate cockroaches.
 Patient Education
• Home peak flow measurements
• Personal asthma management plan
• Exposure avoidance
• Inhaler use
• Relaxation/breathing techniques
• Advise of young atopic people regarding
future job: They should not become
woodworkers or bakers