Transcript Asthma - University of Pretoria

Asthma
SS Visser, Lung Unit, UP
Contents
 Definition
 Disease Pattern
 Prevalence
 Mortality
 Etiology
 Pathogenesis
 Triggers of acute attacks
Contents
 Pathophysiology
 Manifestations of Resp failure
 Diagnosis: clinical,physiologic,immunologic
and radiologic
 Differential diagnosis
 Management
Definition
 Chronic inflammatory disease of airways
(AW)
  responsiveness of tracheobronchial tree
 Physiologic manifestation: AW narrowing
relieved spontaneously or with BD  Cster
 Clinical manifestations: a triad of paroxysms
of cough, dyspnea and wheezing.
Disease Pattern
 Episodic --- acute exacerbations interspersed
with symptom-free periods
 Chronic --- daily AW obstruction which may
be mild, moderate or severe  superimposed
acute exacerbations
 Life-threatening--- slow-onset or fast-onset
(fatal within 2 hours)
Prevalence
 All ages, predominantly early life
 Adults: 2-5% population
 Children: 15% population
 50% dx <10y,85% dx <40y, 15% dx > 40y
 2:1 male/female preponderance in childhood
Mortality
 Fatal asthma 1-7% asthmatics
 ing death rate ?abuse of inhaled BDs
 Risks for death:previous life-threatening
asthma, severe disease, recent hospitalization
or emergency room Rx, non-compliant and
confusion re Rx, under- treatment with
Corticosteroids, discontinued Rx, severe AW
hyperreactivity.
Etiology
 Allergic/atopic/early onset asthma---rhinitis,
urticaria,eczema,(+)skin tests,IgE,(+) response to
provocation tests with aeroallergens.
 Idiosyncratic/non-atopic/late onset asthma--- no
allergic diseases,(-)skin tests,normal IgE, symptoms
when upper resp infection, sx lasting days or
months.
 Mixed group---usually onset later in life
Pathogenesis - 1
 Non-specific AW hyperreactivity:
Sx more severe & persistent
Nocturnal  early awakening with dyspnea
diurnal fluctuation in lung function
Unstable lung function
 BD response,  therapeutic needs
 Cause of hyperreactivity = inflammation
Pathogenesis - 2
 Dual AW response to AG challenge
1.Early bronchospastic response- type1reaction
within min after IH of AG:
Mechanism: IH of aeroallergensensitizatiom
formation of IgE & expression on mast cells
re-exposure to AG mast cell degranulation &
mediator release bronchospasm
Pathogenesis - 3
2.Late-bronchospastic reaction: in 30-50%, 6-10
hours after AG exposure. Minority only a late
response
Mechanism: recruitment of E, N, L and macrophagesrelease lipid mediators(PG E2, F2 ,D2; LT
C,D,E , PAF), O2radicals, toxic granule proteins,
cytokines (TH1:IL-2, IFN; TH2: IL-4, IL-5)
bronchoconstriction, vascular congestion,
mucosal edema, mucus production, mucociliary
transport.
Pathogenesis - 4
 Chronic asthmatic response:
Destruction of AW epithelium by toxic granule
contentsepithelial shedding into bronchial lumen
exposure of sensory nerve endings and imbalance
in cholinergic and peptidergic neuronal control
AW remodelling with subendothelial fibrosis,
goblet cell hyperplasia, smooth muscle hypertrophy, vascular changes fixed AW obstruction.
Triggers of acute asthmatic
episodes
 Allergens - pollen
 Pharmacol stimuli such
as aspirin, NSAIDS, adrenergic blockers,
preservatives,col agent
 Environment pollutionozone, SO2, NO2
 Occupational- metal
salts, biol enzymes
 Infection- resp viruses
 Exercise –IH cold dry
airthermally-induced
hyperemia and microvascular engorgement
 Emotional stress
Pathophysiology
 Reduction in AW diameter AW resistance 
FeV and flow rates hyperinflation work of
breathing altered respiratory muscle Fx and
elastic recoil abnormal ventilation
 Vascular congestion and edema of bronchial walls
abnormal perfusion
 V/P mismatch altered blood gases hypoxemia
and hypocapnia with respiratory alkalosis, but with
impending ventilatory failure  normocapnia and
later hypercapnia and respiratory acidosis
Manifestations of respiratory
failure
 Hypoxemia: cyanosis- very late sign, not
dependable
 Hypercapnia: sweating,
tachycardia,widened pulse pressure
 Acidosis: tachypnea
 Blood gases the only accurate assessment of
ventilatory status
DIAGNOSIS : CLINICAL
 Episodic asthma: Paroxysms of wheeze, dyspnoea and
cough, asymptomatic between attacks.
 Acute severe asthma: Upright position, use accessory resp
muscles, can’t complete sentences in one breath, tachypnea
> 25/min, tachycardia > 110/min, PEF < 50% of pred or
best, pulsus paradoxus, chest hyperresonant, prolonged
expiration, breath sounds decreased, inspiratory and
expiratory rhonchi, cough.
DIAGNOSIS : CLINICAL
 Life-threatening features: PEF < 33% of pred or best,
silent chest, cyanosis, bradycardia, hypotension, feeble
respiratory effort, exhaustion, confusion, coma, PaO2 < 60,
PCO2 normal or increased, acidosis (low pH or high [H+]).
 Chronic asthma: Dyspnea on exertion, wheeze, chest
tightness and cough on daily basis, usually at night and early
morning; intercurrent acute severe asthma (exacerbations)
and productive cough (mucoid sputum), recurrent respiratory infection, expiratory rhonchi throughout and
accentuated on forced expiration.
DIAGNOSIS : PHYSIOLOGIC

1.
2.
3.
Demonstration of variable airflow obstruction with
reversibility by means of FEV1 and PEF measurement
(spirometer and peak flow meter).
FEV1 < 80% of pred – PEF < 80% of pred.
Reversibility: A good bronchodilator response is a 12%
and 200ml improvement in FEV1 20 min after inhalation
of 200ug salbutamol (2 puffs).
Diurnal peak flow variation: Normal variation:
Morning PEF 15% lower than evening PEF. With asthma
this variation is > 15% (morning dipping).
DIAGNOSIS : PHYSIOLOGIC
4.
Provocation studies:
(a)
Exercise: A 15% drop in FEV1 post exercise
indicates exercise induced asthma.
(b)
Metacholine challenge: A 20% reduction in
FEV1 at Metacholine concentrations < 8mg/ml
indicates bronchial hyperreactivity.
This is expressed as a PC20 value of eg 0.5mg/ml (= a
20% reduction in FEV1 at 0.5mg/ml Metacholine).
DIAGNOSIS :
IMMUNOLOGIC




Skin prick wheal and flare response.
IgE and RAST.
Eosinophil cationic protein (ECP).
Peripheral blood and sputum eosinophilia.
DIAGNOSIS : RADIOLOGY
 Chest XR may be normal between attacks.
 With attacks hyperinflation may be found.
 In complicated asthma segmental lobar collapse (mucous
plugs) and pneumothorax can occur.
DIFFERENTIAL DIAGNOSIS
1.
2.
3.
4.
5.
6.
7.
8.
Upper airway obstruction – glottic dysfunction.
Acute LV failure – pulmonary oedema.
Pulmonary embolism.
Endobronchial disease.
Chronic bronchitis.
Eosinophilic pneumonia.
Carsinoid syndrome.
Vasculitis.
MANAGEMENT 1
 Avoidance of allergen and triggers – may be impractical
 adjust Rx.
 Occasional asthma: Rarely symptomatic  2 agonist prn.
 Mild intermittent asthma (episodic): 2 agonist prn + low
dose IH corticosteroid.
 Mild persistent asthma: 2 agonist prn + high dose IH
corticosteroid or long acting 2 agonist + low dose IH
corticosteroid.
 Moderate persistent asthma: 2 agonist prn + high dose IH
corticosteroid + long acting 2 agonist or SR theophylline.
MANAGEMENT 2
 Severe, persistent asthma 2 agonist prn + high dose IH
corticosteroid + long acting 2 agonist + SR Theophylline +
oral corticosteroids.
 Step up: If uncontrolled at any severity level, oral steroids
– Prednisone 30-40-mg/day for 7-14 days.
 Step down: When stable for at least 3 months – reduce or
stop oral steroids first.
 Leukotriene antagonists: for patients with aspirin/NSAIDS
induced asthma. May also be added on for severe persistent
asthma or in pts with steroid related side effects such as
growth retardation or non-responsiveness to IHS or to allow
low dose IHS instead of high dose.
MANAGEMENT 3

Acute severe asthma:
1. Immediate Rx: O2 40-60% via mask or cannula + 2
agonist (salbutamol 5mg) via nebulizer + Prednisone tab
30-60mg and/or hydrocortisone 200mg IV. With lifethreatening features add 0.5mg ipratropium to nebulized
2 agonist + Aminophyllin 250mg IV over 20 min or
salbutamol 250ug over 10 min.
2. Subsequent Rx: Nebulized 2 agonist 6 hourly +
Prednisone 30-60mg daily or hydrocortisone 200mg 6
hourly IV + 40-60% O2.
MANAGEMENT 4
 No improvement after 15-30 min: Nebulized 2 agonist
every 15-30 min + Ipratropium.
 Still no improvement: Aminophyllin infusion 750mg/24H
(small pt), 1 500mg/24H (large pt), or alternatively
salbutamol infusion.
 Monitor Rx: Aminophyllin blood levels + PEF after 15-30
min + oxymetry (maintain SaO2 > 90) + repeat blood gases
after 2 hrs if initial PaO2 < 60, PaCO2 normal or raised and
patient deteriorates.
 Deterioration: ICU, intubate, ventilate + muscle relaxant.