OBSTRUCTIVE PULMONARY DISEASE

ASTHMA
By

PROF DR TAHIR SIDDIQUE

LEARNING OUTCOMES

At the end of this lecture the students will be able to understand the core concepts of
Asthma along with
The Definition of Asthma- The airway hyper reactivity with reversible airflow
obstruction
Mechanism and pathogenesis of the asthma – Genetic determinants along with
environmental factors ----------
Sign and symptoms of the disease – dyspnoea, wheeze, chest tightness, cough ---

Investigations --- Spirometry - with and without bronchodilatation, ABGs, Exercise

effects on FEV1, blood Eosinophilia, Serum IgE level ----------
Management of mild, moderate, severe and life threatening asthma -----

Disease scenario and the way to sum-up their answers --------

BRAIN STROMING
SCENARIO -1

 A 19 years boy presented in medical OPD with the presenting complaints of

breathlessness, chest tightness, wheezing and cough from last two weeks. His
symptoms usually worse at night or early morning. He experienced these
symptoms at least thrice in a week. On examination his respiratory rate was
16/min, there was occasional wheeze, rest of the clinical examination was
normal.
a) What is the most likely diagnosis?
b) How will you investigate this case?
c) What will be the best treatment for this patient
SCENARIO 2

A 27 years male patient presented in medical OPD with H/O Cough from last two
months. Clinical examination was normal. He was worked up for pulmonary
tuberculosis but no evidence for any infective respiratory disease was found. The
physician ordered spirometery. FEV1 was found <80% of the predictive value.

What is the most likely diagnosis?

 Rising/ Confusing / Conflicting Issues

 How will you define Mild, Moderate and Severe Asthma

 Which investigation will you carry out before putting the patient on treatment for
acute severe / Life threatening Asthma.

 What are the different parameters that will help you to decide about mechanical
ventilation.
ASTHMA – DEFINITION AND FEATURES

 Asthma is characterized by airway hyper-responsiveness with

reversible airflow obstruction – usually secondary to chronic
inflammation of the airways

 It is characterized by recurrent episodes of wheezing, chest

tightness, breathlessness and cough usually at night or early
morning

 Asthma affects all age group

ASTHMA – PREDISPOSING FACTORS

 The development and course of asthma and response to treatment

are influenced by genetic determinants and environmental factors

 The potential roll of indoor, outdoor allergens, microbial agents,

breast feeding, diet, vitamins, tobacco smoke, obesity and air
pollution have been explored but no clear consensus has
developed.
ASTHMA – PATHOPHYSIOLOGY

 THE AIRWAY HYPER-REACTIVITY (AHR) – it is the tendency of the airways to

become narrow excessively to the trigger that have no or little response to the
normal individuals – is integral in the diagnosis of asthma and chronic
inflammation of the airways
 THE RELATIONSHIP BETWEEN ATOPY AND PROPENSITY TO PRODUCE IgE is well
established by skin prick test.
 THE COMMON ALLERGENS are house dust mites, pets, insect pests and fungi
 In NSAIDS INDUCED ASTHMA the use of salicylates results the inhibition of cyclo-
oxygenase enzymes and preferentially shunting metabolism of arachidonic acid
through lipoxygenase pathway with resultant production of asthmogenic cysteinyl
leukotrienes
ASTHMA – PATHOPHYSIOLOGY

IN EXERCISE INDUCED ASTHMA

 The hyperventilation results water loss from the pericellular line fluid of
the respiratory mucosa in turn triggers release of mediators
 Heat loss from respiratory mucosa may also important to promote
respiratory bronchospasm
IN PERSISTENT ASTHMA
 A chronic and complex inflammatory response ensues,
characterized by inflex of numerous inflammatory cells
 The transformation and participation of airway structural cells, and
the secretion of airway cytokines, chemokines and growth factors.
 The asthma is characterized by airway eosinophilia, neutrophilic
inflammation predominate in some asthmatics while in other
scanty inflammation is observed (Pauci – Granulocytic Asthma)
 ASTHMA – SYMPTOMS
The classical symptoms of asthma are
1. Cough
2. Chest tightness
3. Dyspnea
4. Wheeze
Asthma characteristically display diurnal pattern. Dyspnea and cough is usually worse in the
early morning.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) (Previously known as

Churg Straus Syndrome)
 It usually manifest as dyspnea, cough, wheeze along with nasal allergies (Polyps),
sinusitis, eczema, skin rash, gastrointestinal bleedings
 Some patients with Asthma have the similar inflammatory response in the upper airways.
Care full enquiry should be made for the history of sinusitis, sinus headache, blocked or
running nose with loss of sense of smell
ASTHMA – SYMPTOMS
COUGH VARIANT ASTHMA
 Cough may be the dominant and some time only symptom that cause the delay in diagnosis

Drug induced asthma

 ß adenoreceptor antagonist
 Asprin
 NSAIDS
 Contraceptive Pills
 Prostaglandin F2∞
 Food and alcohol contain salicylates
 Betal nuts contain arecoline

 In severe asthma, more common in women, allergic trigger is less common in the
airways instead neutrophilia predominate
 ASTHMA – DIAGNOSIS

Compatible clinical history by either / or

1. Baseline Spirometry to measure FEV1 and FVC to assess underlying status and the
severity

2. FEV1 > 12 % ( or 200 ml) increase following administration of bronchodilators / a

trial of glucocorticoids. Greater confidence is gained if the increase is > 15% or
400ml

3. Diurnal variation of > 20% > 3days in a week for 2 weeks on PEF diary

4. 20% decrease in FEV1 after 6 minutes of exercise

5. An elevated FeNO (exhaled NO) in glucocorticoid naive patient indicate

Eosinophilic airway inflammation. A value of > 50 PPB in adults and 35 PPB in
children supports the diagnosis of Asthma and indicate that the patient may
respond to glucocorticoids
ASTHMA – DIAGNOSIS

6. The diagnosis may be supported by the presence of

 Blood eosinophilia
 Atopy by the demonstration of Skin Prick test
 Measurement of total or allergen specific IgE

7. X-ray Chest is usually normal. Lobar Collapse may be present when the
mucous plug obstruct the large bronchus. If accompanied by the presence of
flitting infiltrates is suggestive for the diagnosis of Allergic
Bronchopulmonary Aspergillosis
 ASTHMA – MANAGEMENT

The goal of treatment should be to obtained and maintained a good control of symptoms
 SELF TREATMENT
1. Patients should be encouraged to take the responsibility of managing their own disease.
2. A key concept of self management is patient education, ensuring that the patient should understand the
relationship between the symptoms and inflammation, key symptoms such as nocturnal wakening and indication
of medicines

 AVOIDENCE OF PRECIPITATING FACTORE

1. This is particularly helpful in management of occupational asthma especially for atopic patients.
2. House dust mites exposure may be reduce by replacing floor carpets with board flooring or changing bed sheets
with mites impermeable sheets.
3. Smoking should be stopped as it encourages airway sensitization and glucocorticoid resistance.
4. Many patients are sensitized to ubiquitous aeroallergens so in these patients this strategy is not very helpful in
such patients.

 REGULAR PREVENTOR
The initial therapy for asthma is inhaled glucocorticoids in a low dose 400 µg however higher doses may be required
for smokers with asthma.
 ASTHMA – MANAGEMENT
 INITIAL ADD ON THERAPY
1. If asthma remains uncontrolled despite regular preventer therapy, the long acting ß2
agonist (LABA) should be added in combination with ICS/LABA to prevent inadvertent
use of LABA and to prevent sudden asthma death.
2. The rapid acting LABA formoterol should be used as regular and preventer therapy.
 ADDITIONAL ADD ON THERAPY
If asthma remains uncontrol despite initial add on therapy the patient asthma status should
required a detailed review
 No response to LABA – then it should be stopped and increase the dose of inhaled
glucocorticoids 800µg
 If there is partial response to LABA but asthma control is still poor then increase the dose
of inhaled glucocorticoids to medium dose (800µg) and consider leukotriene antagonist
(LTRA) or slow release theophylline preparation.
 ASTHMA – MANAGEMENT

 HIGH DOSE THERAPIES

1. If the add on therapy is ineffective then it should be discontinued.
2. Increase the dose of inhaled glucocorticoids (2000µg BDP) or equillant daily dose.
3. Trial of LTRA, Long acting anti muscarinic agents (LAMA), theophylline or slow release oral ß2
agonist should be used
 CONTINUOUS OR FREQUENT USE OF STEROIDS
1. In patients with suboptimal response to therapy, oral glucocorticoids should be given in
lowest possible dose. The patients on steroids >3 months or requires 3 – 4 courses of steroids
in a year are prone to osteoporosis and Bisphosphonate should be added in this patients.

2. The patients who required long term steroids should be considered for biological therapies.
 The patients with IgE driven Atopic Asthma Omalizumab (anti IgE) should be given
 The patients with Eosinophilic form of Asthma should be considered for Benralizumab
(anti-IL5r), Mepolizumab (anti-IL5), Reslizumab (anti-IL5) or Dupiliumab (anti-IL4/13)
 MANAGEMENT OF EXACERBATIONS OF ASTHMA

1. The course of asthma may be punctuated by exacerbations with increased symptoms,

deterioration in lung function, and an increase in airway inflammation develop in hours.

 Exacerbations are most commonly precipitated by viral infections but molds, pollens
(particularly following thunderstorms) and air pollution are also implicated.
 Most attacks are characterized by a gradual deterioration over several hours to days

2. Some appear to occur with little or no warning: so-called BRITTLE ASTHMA. An important
minority of patients appear to have a blunted perception of airway narrowing and fail to
appreciate the early signs of deterioration.
 MANAGEMENT OF MILD TO MODERATE EXACERBATIONS
Doubling the dose of inhaled glucocorticoids does not prevent an impending exacerbation.
Short courses of at least 5 days of ‘rescue’ glucocorticoids (prednisolone 40–50 mg/day) are
therefore often required to regain control.

 Tapering of the glucocorticoid dose to withdraw treatment is not necessary, unless it has been given
for more than 3 weeks.

Indications for ‘rescue’ courses include:

 Symptoms and PEF progressively worsening day by day, with a fall of PEF below 75% 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 that are sufficiently severe to require treatment with nebulized bronchodilators
 IMMEDIATE ASSESSMENT OF ACUTE SEVERE ASTHMA
Acute severe asthma
PEF 33%–50% predicted (<200ml/min)
Heart rate ≥110 beats/min
Respiratory rate ≥25 breaths/min
Inability to complete sentences in 1 breath

Life-threatening features
PEF <30% predicted (<100ml/min) Cyanosis
SpO2 <92% or PaO2 <8kpa (<60m)mmHg especially if Feeble respiratory effort
treated with oxygen) Bradycardia or arrhythmias
Normal or raised PaCO2 Hypotension
Silent Chest
Exhaustion
Delirium
Coma
Near-fatal asthma
Raised PaCO2 and/or requiring mechanical ventilation with raised inflation pressures
PRE REQUISITES FOR

MANAGEMENT OF ACUTE SEVERE ASTHMA

 Measurement of PEF is mandatory, unless the patient is too ill to

cooperate, and is most easily interpreted when expressed as a
percentage of the predicted normal or of the previous best value
obtained on optimal treatment
 Arterial blood gas analysis is essential for those patients with life-
threatening or near-fatal asthma to determine the PaCO2 , a
normal or elevated level being particularly dangerous.
 A chest X-ray is not immediately necessary, unless pneumothorax is
suspected. Treatment includes the following measures:
 MANAGEMENT OF ACUTE SEVERE ASTHMA

 Oxygen.
 Controlled supplemental oxygen should be administered to maintain SaO2 94%–98%. The presence
of a high PaCO2 should not be taken as an indication to reduce oxygen concentration but as a
warning sign of a severe or life-threatening attack. Failure to achieve appropriate oxygenation is an
indication for assisted ventilation.
 High doses of inhaled bronchodilators.
 Short-acting β2 -agonists are the agent of choice. They can be administered either via multiple
doses of a metered-dose inhaler via a spacer device, or via a nebuliser driven by oxygen.
Ipratropium bromide provides further bronchodilator therapy and should be added to if there is a
failure to respond to salbutamol or in life-threatening attacks.
 Systemic glucocorticoids.
 These reduce the inflammatory response, reduce mortality, subsequent hospital admission and
requirement for bronchodilators. They should be administered to all patients with an acute severe
attack. They can usually be administered orally as prednisolone but intravenous hydrocortisone
may be used in patients who are vomiting or unable to swallow.
 MANAGEMENT OF ACUTE SEVERE ASTHMAMANAGEMENT OF ACUTE SEVERE
ASTHMA

INTRAVENOUS FLUIDS
 There is no evidence base for the use of intravenous fluids but many patients are
dehydrated due to high insensible water loss and may benefit.
INTRAVENOUS POTASSIUM
 Potassium supplements may be necessary to counteract hypokalemia caused by
repeated doses of beta-agonists.
INTRAVENOUS MAGNESIUM
 If patients fail to improve, a number of further options may be considered, including
intravenous magnesium
MANAGEMENT OF ACUTE SEVERE ASTHMAMANAGEMENT OF
ACUTE SEVERE ASTHMA

INTRAVENOUS AMINOPHYLLINE
 For patients with life-threatening or near-fatal attacks intravenous aminophylline is
considered, although cardiac and therapeutic drug level monitoring is
recommended.
PEF MONITORING
 PEF should be recorded 15–30 minutes after starting therapy and thereafter (every
4–6 hours) and pulse oximetry should be monitored to ensure that SPaO2 94%–
98% is maintained
ABGS
 Repeat arterial blood gases are necessary if the initial PaCO2 measurements were
normal or raised, the PaO2 was below 8 kPa (60 mmHg) or the patient deteriorates.
 PROGNOSIS
 The outcome from acute severe asthma is generally good but a considerable number of deaths
occur in young people and many are preventable.
 Failure to recognize the severity of an attack on the part of either the assessing physician or the
patient, contributes to delay in delivering appropriate therapy or to under-treatment.
 Prior to discharge, patients should be stable on discharge medication (nebulized therapy should
have been discontinued for at least 24 hours) and the PEF should have reached 75% of predicted
or personal best.
 The acute attack should prompt a look for and avoidance of any trigger factors, the delivery of
asthma education and the provision of a written self-management plan.
 The patient should be offered an appointment with a general practitioner or asthma nurse
within 2 working days of discharge, and follow-up at a specialist hospital clinic within a month.
SCENARIO -1

 A 19 years boy presented in medical OPD with the presenting complaints of

breathlessness, chest tightness, wheezing and cough from last two weeks. His
symptoms usually worse at night or early morning. He experienced these
symptoms at least thrice in a week. On examination his respiratory rate was
16/min, there was occasional wheeze, rest of the clinical examination was
normal.
a) What is the most likely diagnosis?
b) How will you investigate this case?
c) What will be the best treatment for this patient
 SCENARIO -1

a) Mild intermittent bronchial Asthma / Bronchial Asthma

b) ANS
 Spirometery
 FEV1 > 15% increase following administration of a bronchodilator / trial of corticosteroids
 > 20% diurnal variation on > 3 days in a week for 2 weeks on PEF diary
 FEV1 > 15 % decrease after 6 minutes of exercise

 Measurement of Allergic status

 Skin prick test
 Allergen specific IgE
 CBC with peripheral blood Eosinophilia

 Radiological Examination
 CXR – normal or hyperinflation of lung fields. Flitting infiltrates may suggest allergic bronchopulmonary aspergilosis

 Airway Eosinophilic inflamation Assessment

 Induced sputum eosinophilic count of greater than 2% or exhaled breath NO concentration
 SCENARIO -1
c) ANS
 STEP 1 (Mild intermittent bronchial Asthma)
Short acting inhaled β2 agonist therapy
--------------------------------------------------
 STEP 2 (Regular Preventer Therapy)
Step 1 + inhaled corticosteroids, (Beclomethasone diproprionate 400μg)
--------------------------------------------------
 STEP 3 (Initial Add On therapy)
LAβ2A + inhaled corticosteroids 800μg + Leukotriene receptor antagonist or SR Theophyline

 STEP 4 (Persistently poor response)

LAβ2A + inhaled corticosteroids 2000μg + Leukotriene receptor antagonist + SR Theophyline or β2 agonist tablets

 STEP 5 (Persistently poor response)

Oral Steroids + LAβ2A + inhaled corticosteroids 2000μg + Leukotriene receptor antagonist + SR Theophyline or β2
agonist tablets
SCENARIO 2

A 27 years male patient presented in medical OPD with H/O Cough from last two
months. Clinical examination was normal. He was worked up for pulmonary
tuberculosis but no evidence for any infective respiratory disease was found. The
physician ordered spirometery. FEV1 was found <80% of the predictive value.

What is the most likely diagnosis?

SCENARIO 2

ANS:

Cough Variant Bronchial Asthma

THANKS FOR BEING WITH
ME