Transcript bronchial asthma - The Medical Post

ALOK SINHA
Department of Medicine
Manipal College of Medical Sciences
Pokhara, Nepal
Chronic airway inflammation & increased
airway hyper-responsiveness leading to
symptoms of



Wheeze
Chest tightness and
Dyspnoea
Characterised functionally by the presence
of airflow obstruction which is
variable over short periods of time
reversible with treatment
How common it is ?
300 million people world-wide suffer
from asthma
additional 100 million may be
diagnosed with asthma by 2025
Impact on society?
The socio-economic impact of asthma is
enormous
Poor control leads to
• days lost from school or work
• hospital admissions
• premature death
Two types of Asthma
Classification
1. Early onset Asthma
(atopic, allergic or extrinsic)
More common
2. Late onset Asthma
(non atopic or intrinsic)
Two types of Asthma
Early onset Asthma
• Onset young age
• Allergy present
• Other allergic diseases
present- eczema,
alllergic rhinitis
• Increased IgE in
serum
• Positive skin
hypersensitivity
test
Late onset Asthma
•
•
•
•
Onset in adults
No history of allergy
Normal IgE lavels
Negative skin
hypersensitivity test
Etiology
Results from Interplay of
environmental
and
genetic factors
stem cells
Lymphocytes
Mature in B.marrow to become
“B LYMPHOCYTE”
react with bacteria
plasma cells
Factory:
Bone marrow
Thymus
Produce antibody
“T Lymphocyte”
Helper T cells
(CD4 surface protein)
Cytotoxic T cells
Humoral immunity
recognise the antigen with
the(Fight
help against
of macrophages
bacteria)
activated lymphocytes enter the
tissue and meet antigen again
results in multiplication and secretion
of cytokines or immunoglobins in order
to destroy the antigen
Th1 cells - involved in
cell mediated immunity.
Produce
interferon gamma,
interleukin 2 & TNF beta.
Th2 cells: play a role in
humoral responses
responsible for Atopy and
allergy
Cellular immunity
Against virus, fungi, TB & cancer
• In utero Th2 bias of T
lymphocytes
• Directes the immune
system towards an
allergic type of response
• Propensity to produce
IgE-and asthma
• Changes to Th1 bias of T
lymphocytes when
encounter respiratory
infection
• Immune system produces
IgM & IgG type of
antibodies necessary for
fighting against bacterial
infections
• Doesn’t react to allergens
Pathophysiology
Pathophysiology
Involves the following components
(1) Bronchial hyper responsiveness
(2) Airway inflammation
(3) Intermittent airflow obstruction
Bronchial hyper responsiveness
• An exaggerated response to numerous
exogenous and endogenous stimuli
• direct stimulation of airway smooth muscle
• indirect stimulation by pharmacologically active
substances from mediator-secreting cells like
mast cells
 Degree of airway hyper responsiveness
correlates with clinical severity of asthma
Inflammation
 May be
• acute
• subacute
• chronic
Cells involved in release of
mediators
Principal cells identified in airway inflammation
• Mast cells
• Eosinophils
• Epithelial cells
• Macrophages
• Activated T lymphocytes
• Neutrophils
 Cell-derived mediators
• Histamine
• Leukotrienes (potent constrict. agents)
• Various cytokines
It cause:
• Initially -smooth muscle spasm
• Latter on – remodelling of the airway
(structural changes)
Releases Histamine. Responsible for
early phase response
Presence in air ways indicates steroid
responsiveness
Increased number present during
Asthma exacerbation.Presence
indicates corticosteroid resistance.
Present in severe & near fatal asthma
Involved in remodeling of airways
Different phases of Bronchial asthma
 Early phase
 Delayed phase
 Chronic phase
Early phase
Bronchoconstriction & intermittent air
flow obstruction
• Allergens through immunoglobulin E–
dependent mediator interacts with mast
cells & cause release of
• Histamine
• Cysteinyl leukotrienes
(Therapeutic response in a short period)
Delayed phase
Late asthmatic response 6-24 hours following
allergen exposure
 Influx of numerous inflammatory cells

• lymphocytes
• mast cells
• neutrophils
There is secretion of an array of
• cytokines
• chemokines
• growth factors
It leads to
• associated oedema
• mucous plugging
• epithelial damage
(therapeutic response takes longer)
• smooth muscle hypertrophy & hyperplasia
• thickening of basement membrane
(May be incomplete therapeutic response )
Chronic phase
 Mucous plug formation
• exudate of serum proteins and cell debris take
weeks to resolve
 Airway remodeling
• structural changes due to long-standing
inflammation
• May profoundly affect the extent of
reversibility of airway obstruction
Some subtypes of Asthma
Exercise-induced asthma
 Bronchospasm brought about by exercise
 May be a component of overall Asthma
 Or a sole manifestation in as many as 50% of
patients - exercise- asthma variant
 Vigorous physical activity triggers acute broncho
spasm in persons with heightened airway reactivity
• Tends to adapt subseqently - tachyphylaxis
• Episodic asthma
• Asthmatic episodes with asymptomatic periods
• Chronic asthma
• Symptoms present through out
• Nocturnal asthma
• cough and wheeze disturb sleep
• Cough-variant asthma
• Cough dominant symptom
• lack of wheeze or breathlessness
Occupational asthma
• Should be considered in adult asthmatics
• If symptoms improve during time away
from work, e.g. weekends or holidays
• Atopic individuals and smokers are at
increased risk
• Removal from exposure leads to improved
prognosis
Dynamic clinical syndrome with a variety
of features
Recurrent episodes of

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Wheezing
Chest tightness
Breathlessness
Cough
Precipitated by
• exercise in cold weather
• exposure to airborne allergens &
pollutants
• viral upper respiratory tract infections
Factors aggravating asthma
Factors aggravating asthma
Drugs
•
•
•
•
Beta blockers- even eye drops
Aspirin
ACE Inhibitors
Sulphonamides
Inhaled allergens
•
•
•
•
Pollen
Animal dander
Cockroach allergens
Occupational allergens such as chemicals,
fumes, particles of industrial materials
• Indoor fungi
• House dust mites
Allergic bronchopulmonary aspergillosis
(ABPA)
Hypersensitivity reaction to Aspergillus
fumigatus that occurs in patients with


asthma
less commonly - cystic fibrosis.
Immune responses to Aspergillus antigens
cause airway obstruction and aggravation of
symptoms and signs of asthma leading to
frequent, recurrent asthma exacerbations
Diagnosis confirmed by


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Aspergillus skin testing
measurement of IgE levels
A. fumigatus–specific antibodies
Treatment


corticosteroids
Itraconazole in refractory patients
• Allergy to certain foods
• Sea foods
• any food item
• Respiratory infections
• Resp. virus
• Sinusitis
• G.E.R.D.
• Emotional factors or stress
Physical signs in chest
 Tachypnoea with accessory muscles working
 Percussion note hyper resonant
 Breath sounds vesicular with prolonged
expiration
 Polyphonic ronchi – mostly expiratory
 Silent chest during very severe attack
(hyperinflated lungs)
 In between the attacks – no or very minimal
findings
Investigations
DIAGNOSIS OF ASTHMA
Compatible clinical history + either/or Obstructive picture (FEV1:FVC <70%) +
1. FEV1 ≥ 15% (and 200 ml) increase following
administration of a bronchodilator/trial of
corticosteroids
2. > 20% diurnal variation on ≥ 3 days in a week
for 2 weeks on PEF diary
3. FEV1 ≥ 15% decrease after 6 mins of
exercise
PEFR Measurement
 Peak flow meters -simple method of confirming
the diagnosis
 Patients should record peak flow readings
 after rising in the morning
 before retiring in the evening
 Diurnal variation in PEF of more than 20% is
diagnostic
 Magnitude of variability provides indication of
disease severity
 Is generally unhelpful
 May point to alternative diagnoses
 Acute asthma is accompanied by
• hyperinflation
• lobar collapse may be seen if mucus has
occluded a large bronchus
Measurement of allergic status
1. Elevated sputum or peripheral blood
eosinophil count
2. Serum total IgE is elevated in atopic
asthma
3. Skin prick tests are simple and provide a
rapid assessment of atopy
Management
THE GOALS OF ASTHMA
MANAGEMENT
 Achieve
and maintain control of symptoms
 Prevent asthma exacerbations
 Maintain pulmonary function as close to
normal as possible
 Avoid adverse effects from asthma
medications
 Prevent development of irreversible airflow
limitation
 Prevent asthma mortality
• A household pet
• House dust mite
• Reduce fungal exposure
• Eliminate cockroaches
• Stop smoking
• Regular aerobic exercise
• Breathing exercises
• Relaxation techniques
Specific treatment
Severity of Br. Asthma
Symptoms noct. Sympt
• Stage 4
Continuous
Frequent
Severe
FEV1/PEFR
<60% predicted
variability >30%
• Stage 3
Daily
Moderate
>1 time /week
60-80% predicted
variability >30%
• Stage 2
>1 /week
Mild
but not daily
>2 times
a month
>80% predicted
variability 20-30%
• Stage 1 <1 time /week <2 times
Intermittent
a month
>80% predicted
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© 2005 Elsevier
Stage I
Short-acting Beta2 agonists
Salbutamol- M.D.I. 100 mcg/dose- 2 puffs
max 8 inhalation/day
Rota haler- 400 mcg – one capsule
Resp solution for nebulizer 5mg/ml
Terbutaline
Others
Fenoterol
Rimiterol
Stage II
Inhaled corticosteroids
Beclometasone dipropionate (BDP) 400 μg or
equivalent per day in adults. Increased– 800 μg
Others are:
Budesonide (BUD)
Fluticasone 100-250 μg/day
Mometasone - provide equal clinical activity to
BDP/BUD at half the dosage.
SideEffects
Inhaled corticosteroids may cause
An infection in the mouth
Cough, or hoarseness
Sometimes headache
• Use a spacer or holding chamber to avoid
these problems
• Rinsing mouth after inhaling the medicine
Will help to prevent mouth infections
Make shift spacer
Difference between
Short-acting Beta2 agonists
Inhaled Cortico steroids
• Only relieve symptoms • Can relieve the
symptoms
• Does not affect the
• Affect the underlying
underlying pathology
• Does not alter the
course of the disease
pathology
• Alter the course of the
disease
For stage III
add-on therapy should be considered beyond an
ICS dose of 800 μg/day BDP (or equivalent) in
adults
Long acting beta 2 adrenoceptor agonist
Salmeterol- Aerosol inhalation

50 micrograms (2 puffs) bd taken regularly. Can be increased to 100
micrograms bd
Formoterol- Dry powder inhalation

12 micro grams bd taken regularly. Can be increased to 24 micrograms
bd, if required
Leukotriene receptor antagonists
• Montelukast
• 10 mg orally daily may reduce exacerbations
Xanthine derivatives
• Theophyllines
• useful in some patients
• have limited use because of side effects
Step IV
Dose of ICS increased to 2000 μg
BDP/BUD
Nasal corticosteroid preparation used in
patients with prominent upper airway
symptoms
Oral therapy with

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Leukotriene receptor antagonists
Theophyllines
Slow-release β2-agonist
Oral itraconazole should be contemplated
in patients with ABPA
Step V
Prednisolone therapy has to be given
lowest amount necessary to control
symptoms should be given
Patients on long-term corticosteroid
tablets (> 3 months) or receiving more
than three or four courses per year will be
at risk of systemic side-effect
Indications for 'rescue' courses
Symptoms and PEF progressively
worsening day by day
Fall of PEF below 60% of the patient's
personal best recording
Onset or worsening of sleep disturbance
by asthma
Persistence of morning symptoms until
midday
Progressively diminishing response to an
inhaled bronchodilator
Symptoms severe enough to require
treatment with nebulised or injected
bronchodilators
a medical emergency in which there is
acute asthmatic attack with out any
remission in between and is not controlled
by conventional bronchodilators
Clinical features
• Severe dyspnoea with features of airway
obstruction
• Vesicular breath sound with prolonged
expiration
• Expiratory ronchi all over
• Tachycardia with Pulsus paradoxus
• Cyanosis may be present
• Percussion note hyper resonant
Severe Asthma
Life-threatening asthma
Near-fatal asthma
severe Asthma
PEF 30- 50% best or predicted
Respiratory rate >25/min
Tachycardia: heart rate >100/min
Inability to complete sentences in one
breath
Life-threatening asthma
Severe airways obstruction
 PEF <33% best or predicted
 Soft breath sounds or silent chest
Increased work of breathing &
haemodynamic stress
 Exhaustion
 Feeble respiratory effort
 Hypotension (systolic BP <100mmHg)
 Bradycardia or arrhythmia
Ventilation-perfusion mismatch
 Cyanosis
 Hypoxia (SpO2 <92% and/or PaO2
50mm irrespective of inspired O2
concentration)
Ventilatory failure
 Rising PaCO2
 Confusion or coma
Near-fatal asthma
Raised PaCO2
Immediate requirement for ventilation with
raised inflation pressures
Management

Remain calm: reassurance is important
in reducing the patient's anxiety which
may further increase respiratory effort
Treat hypoxia
Treat bronchospasm and inflammation
Treat any underlying cause if present
 infection
 pneumothorax
Assess the need for intensive care
Initial treatment
1. Sit the patient up in bed
2. Oxygen:
 highest percentage available
60% or 15L/min with a high-flow mask


CO2 retention is not a problem in asthmatic
patients (as in COPD)
Maintain O2 sats >92%
3. Nebulized bronchodilators
Salbutamol 5mg or
Terbutaline 10mg

administered with O2 and repeat up to every
15-30 minutes if required
Continuous nebulization of salbutamol
10mg/h if inadequate response to initial
treatment
Add Ipratropium bromide 0.5mg 6 hourly if initial
response to –Beta-2 agonists is poor
Obtain iv access
4. Start Steroids:
Hydrocortisone 200mg Stat followed by 100mg 6-8 hourly
Or
Methylprednisolone
intravenously (steroids should still be used in pregnant
women as the risk of foetal anoxia from the asthma is high)
5. Antibiotics in chest infection
• purulent sputum/ or fever
• abnormal CXR
• raised WBC
6. Adequate hydration is essential
• help prevent mucus plugging
• Ensure an intake (iv or p/o) of 2-3L/day, taking
•
care to avoid overload
Supplement potassium as required
Monitoring progress
Pre- and post-nebulizer peak flows
Repeated arterial blood gases 1-2 hourly
or according to response especially if
SaO2 <93%
If response not brisk or patient's condition is
deteriorating
Continue oxygen and nebulized beta2-agonist
every 15 minutes
7. Magnesium sulphate iv single dose
1.2-2g infused over 20 minutes
8. iv Aminophylline infusion
Loading dose: 250mg (4-5mg/kg) iv in 20 min
Maintenance infusion: 0.5- 0.7mg/kg/h (250mg in 1 litre N saline at 2- 4
ml/kg/h)
9. Consider iv Salbutamol infusion


Loading dose: 100- 300µg over 10 minutes
Maintenance infusion: 5 -20µg/min (5mg in 500ml saline at
1- 3ml/min)
Side Effects:
• tremor
• tachycardia
• hypokalaemia
• hyperglycaemia
10. Summon anaesthetic help
Indications for admission to intensive
care unit
Hypoxia (PaO2 <8kPa (60mmHg) despite
FiO2 of 60%
Rising PaCO2 or PaCO2 >6kPa
(45mmHg)
Exhaustion, drowsiness, or coma
Respiratory arrest
Failure to improve despite adequate
therapy
Further management
Continuous Positive Airway Pressure
(CPAP)
Anaesthetic agents e.g.


Halothane
Ketamine
Improve bronchospasm. useful when
initiating ventilation
Mechanical ventilation
Life saving
High risk of complications overall mortality of
~13%.
Hypotension in ~38%
 Barotrauma
seen in ~14%
• pneumothorax
• pneumo-mediastinum
• subcutaneous emphysema
On-going therapy
Continue nebulized beta2-agonist,
reducing to 4-hourly and withdraw after
24- 48 hours
Peak flow rate should be measured before
and after each nebulizer
Maintain O2 sats >92%
Continue nebulized ipratropium bromide
6-hourly until the condition is improving
Continue steroids, hydrocortisone 100mg
q6h iv switching to 30- 60mg o d oral
prednisolone when able to swallow, and
continue for 10-14 days
Monitor serum K+ daily and supplement
as necessary
Discharge
PEF should be 75% of best without
significant morning dipping
Should be established on inhalers with no
requirement for nebulizers for 24- 48
hours prior to discharge.
Discharge drugs
Prednisolone po 30mg od for 1-3 weeks (plan
gradual dose reduction if treatment >14 days)
Inhaled corticosteroids at high dose (usually
1000-1500µg beclomethasone via spacer) or
equivalent
Restart inhaled long-acting beta2-agonists if
prescribed prior to admission
Oral theophyllines if required
Wrong
Differential diagnosis
Cardiac. asthma (L.V.F.)
Pulmonary oedema
Pneumonia
Pneumo-thorax
Pulmonary Embolism
Anaphylactic reaction
Renal Asthma
Acute Laryngeal Obstruction
a. oedema
b. Foreign body
Anxiety Neurosis


airflow obstruction due to 
inflammation & increased
airway hyper-responsive
ness & bronchospasm
which is
Chronic obstruction of
lung airflow which is
permanent & progressive
over time
 variable over short
periods of time
 reversible with treatment
cause
Mostly by allergens in atopic  Due to the chemical
irritation of the airways
persons
caused by smoke(ing)
Age group

Mostly affects the young
people

Disease of middle aged &
elderly

Pathogenesis
Airway obstruction due to
 Due to
– Smooth muscle spasm
– oedema
– Loss of elastic recoil
– Remodeling of the air way
Clinical features

Chest normal in between
the attacks

Features of air way
obstruction always seen
Complications
Emphysematous changes  Seen after some years
do not occur
 Does not progress to cor  Many cases develop
pulmonale or type II
these complication
respiratory failure

Pulmonary Function Test
Obstructive picture +
1.
FEV1 ≥ 15% (and 200 ml)
increase following administration
of a bronchodilator/trial of
corticosteroids
2.
> 20% diurnal variation on ≥ 3
days in a week for 2 weeks on
PEF diary
3.
FEV1 ≥ 15% decrease after 6
mins of exercise
Obstructive pattern +
1.
Minimal bronchodilator
reversibility (<15%, usually
<10%)
2.
< 20% diurnal variation on ≥ 3
days in a week for 2 weeks on
PEF diary
No change in FEV1: FVC with
exercise (absence of exercise
induced bronchospasm)
3.
X ray chest

Normal in between attacks. Hyper
inflated lungs at the time of acute
attack

Shows
–
–
Emphysematous changes with
bullae
Features of pulmonary
hypertension