Asthma - "Chronic inflamation of Airway -

lead
2
Airway hyper-reactivity > Airway obstruction.

Management of stable patients (not in exacerbation):

7
beclometasone dipropionate 12hr -- s
Step 1- low dose ICS
- I

> formoterol >Fast acting > MART >:81's,

Step 2- low ICS +LABA

-

> Salmoterol - 19
Step 3- Medium ICS + LABA.
Step4- High ICS + LAMA
-
- Tiotropium
-
-

Step 5- Oral prednisolone >

>

>

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 Asthma. MI
obstructive lung disease.
-

> COPD.

Asthma
-

6: 531 Asthma is a disease characterized by intermittent cough, chest

-- I,8)
-

tightness, shortness of breath, and wheezing. These symptoms

result from airway obstruction, which is variable over a short period
of time, or is reversible with treatment. Airway obstruction results
from chronic airway inflammation and airway hyper-reactivity
(AHR); which are the two cardinal features of asthma. Very easy to
= >

·b struction by
exposure to
inflman toy
Epidemiology: ....

Asthma affects 5 – 10% of the adult population (around 360 million

patients worldwide). The incidence is increasing especially in
developed countries.

Pathophysiology:
Histologically, the asthmatic airways show evidence of
inflammation characterized by inflammatory cell infiltrate
(including eosinophils, lymphocytes, mast cells, and neutrophils),
- -

mucosal oedema, smooth muscle hypertrophy, mucus plugging, and

epithelial damage. The inflammation is most intense during
-

exacerbation.
- -
Yes.
19.
I skinpricktest

Many patients are atopic (demonstrating skin prick test reactivity

-

and elevated serum IgE), and in these atopic patients, inhaled

allergens interact with mucosal mast cell, via IgE dependant
mechanism, resulting in release of inflammatory mediators.
Inhalation of the allergen is followed by two-phase (early and late)
-
=>
I
bronchoconstrictive response.
Common examples of these allergens include house dust mites,
->
5~
S
s
pet's dander (such as cats and dogs), pests (such as cockroaches and
fungi) and pollens.->
Is
> not caused by allerges
- it's eosinophilic
-
51
inflamation.
In many other patients, asthma is non-atopic and its pathogenesis is
characterized by complex interaction between inflammatory cells,
ultimately resulting in eosinophilic airway inflammation.
=

1
 = >

Aspirin of NSAIDS, Iss

-> -

·5,0Y Asthma 61 st

cyclooxyy.I1
8185;
~ AA

55 ! 1LiPoXyge...

iii
-

Brancho constrictor & 89 Leukotrienes

=
515 - 21s

However, some patients are characterized by neutrophil-

predominant inflammation.
In aspirin-sensitive asthma, aspirin (or NSAID) inhibit cyclo-
oxygenase, shunting arachidonic acid metabolism through lipo-
oxygenase pathway, resulting in the production of leukotrienes
(broncho-constrictors and inflammatory mediators).
In exercise-induced asthma, hyperventilation results in water loss
from the respiratory mucosa, triggering mediator release.
AHR is related to airway inflammation, which means exaggerated
-
(too easily and too much) bronchoconstriction in response to
triggers that have little or no effect in normal individuals, like
-

histamine, methacholine and mannitol. AHR is integral in the

=> -

diagnosis of asthma.
Airway obstruction results from both airway inflammation and
AHR, and is typically reversible, spontaneously or with treatment.
Longstanding severe disease is associated with airway remodeling,
-

characterized by structural alteration of the airways, including

subepithelial fibrosis, and fixed narrowing of the airways, with
-
-
-

reduced response to bronchodilators.

2
 >
"risk of Asthma.

> - environmental factors.

Aetiology:
Genetic factors play an important role in the predisposition to
asthma, but the marked rise in incidence in the preceding decades
supports a critical influence of environmental factors on disease
-
-

for mature expression. A lot of studies suggested a protective effect for early
-

-IG from
ofImmune- microbial exposure in childhood and breast feeding, and increasing mother.

system
susceptibility in association with obesity, indoor and outdoor
allergen exposure, smoking and air pollution. However, none of
these associations are strongly supported.

in old age.
Clinical picture: ware occur

Asthma can begin in any age. It commonly starts in childhood; and

95/95 50% of adults with asthma recall having asthma in childhood.
-sig Asthma is a disease of variable presentation. In its typical picture,
7
$ S.
is 5.5. the patient has recurrent episodes of breathlessness, wheezing,
=

chest tightness and cough. The attacks are triggered by allergen

- -
-

exposure, exercise (particularly in cold weather), respiratory tract

-
-

infections (commonly viral), dust and pollutants. Sometimes, no

-
=>
>

apparent trigger is identified. These attacks are reversible

spontaneously or with treatment.
Examination may show evidence of airway obstruction (prolonged
expiration and wheezing). Nasal polyps and eczema may be present.
Although some patients are asymptomatic in between the attacks >e
-
- -

(intermittent asthma), many others have continuous wheezing and

-

breathlessness (persistent asthma), but variability is usually present

- -

->"sy
with symptoms fluctuating in severity over time.
A characteristic feature of asthma is the diurnal pattern of
-

symptoms that symptoms tend to worsen in the early morning

(morning dipping). "Nocturnal asthma" is generally a feature of
poorly controlled disease; where symptoms of cough and wheeze
-
-

disturb sleep.
-

Asthma may present with cough as a dominant feature, without

other symptoms. This so called "cough variant asthma" may be

3
 difficult to diagnose. "Drug induced asthma" may result from (or
precipitated by) the use of -blockers (sometimes in eye drops), or
aspirin (and NSAIDs). onchoconfriction.

The classical aspirin-sensitive asthmatic is a middle aged female

with associated rhinosinusitis and nasal polyps (aspirin exacerbated
respiratory disease (AERD)).
Occupational asthma is the most common occupational lung
disease. It is defined as asthma which is related to work
environment, and can be caused by allergic sensitization or non
allergic mechanism. Around 5% of all adult asthma is occupational
and several hundred agents have been identified as potentially
contributing to occupation asthma. Common examples include
- I s

isocyanates, flour and wood dust, latex, paint spray and animals.
-
-

Occupational asthma should be suspected if symptoms are worse

- - -

during working hours and improves on weekends and holidays.

Asthmatic patients are at risk of acute exacerbation of their disease
characterized by marked worsening of their symptoms, that
requires emergency treatment, usually in association with viral
respiratory infections, but also allergen exposure, air pollution or
withdrawal of treatment.

Diagnosis: >
Sess
+
1h
clinical demonstrate obstruction.
The diagnosis of asthma is predominantly clinical and based on
- - -

characteristic history, supported by demonstration of variable

=>

airway obstruction. This is done by pulmonary function test,

which includes:
 Spirometry: measurement of FVC and FEV1 by spirometry
demonstrates airway obstruction and defines its severity.
[Link]
Improvement insof FEV1 by 12% (and 200ml) after
-

bronchodilator administration (or trial of oral

fruit corticosteroids) confirms the diagnosis
.FEV1/FVC <70%
.
- Obstruction
[Link] iims
↓ After bronchodilator(salbutamol). - FEV1 increase (12%).
-> -
- Asthma
i
2 After excercise ->f(1 -> 115:, AHR > Histamine ->
FEx-1?
6min 3
4
↑ 14
PEF 20%-> Asthma

25. S
 PEF 2
215
95.8,85513,;
DEF -> s si li!
& 20%,
10) Asthma

 If spirometry is not available or if the patient has normal

-

pulmonary function on spirometry at the time of

examination, PEF (peak expiratory flowmeter) is an
- - -

inexpensive and simple method of confirming airway

obstruction. A diurnal variation of home record with more
-

than 20% difference is diagnostic (the lowest value

typically being recorded in the morning).
-

too y
onstrite histain
>
 If asthma is clinically suspected but the spirometry is
jm
-

asthy
-

normal, testing for AHR can be useful. Histamine or

-

& methacholine can be administered with sequential increase

iiin concentration. In asthmatics, minimum concentration is

-

S.5
·
sufficient to cause 20% drop in FEV1. Absence of airway
hyperreactivity practically excludes asthma (sensitivity of
-
90%), but positive results is seen in many other diseases,
-

-
like COPD, bronchiectasis and cystic fibrosis.

5
  For patients whose symptoms are exclusively occurring
after exercise, a 6-minute exercise test followed by a drop
of FEV1 by 15% is diagnostic.

-
In general, asthma can be diagnosed in the presence of compatible
history and one of the followings:
1. FEV1  12% (and 200 ml) increase after bronchodilator or
trial of corticosteroids.
2. 20% diurnal variation in PEF daily records
= > > -

3. FEV1  15% decrease after 6 min. of exercise.

-

Other investigations:
Chest X-ray is generally unhelpful in establishing the diagnosis of
= -

asthma (often normal or show hyperinflation of lung fields).

However, it can exclude alternative diagnosis or coexistent
problems. Complications like lobar collapse or pneumothorax are
also diagnosed.

6
 Asthma -> 88515
-
> by History suspected
FENo 818555
I

Allergy testing: Atopy can be confirmed by skin prick test and total FENo>S5

and allergen-specific IgE. I

This is
enough
Peripheral blood and sputum oesinophilia, as well as fraction to diagnosis
exhaled nitric oxide (FENO), are markers of eosinophilic airway of Asthma.
Si !
⑤
marker
-

inflammation and they support the diagnosis of asthma.

-

7300 ->

⑤No,* of eosinophilic
I
Airway infla
·

-
....

Management of stable patients (not in exacerbation):

Effective treatment is available for the majority of cases. The goal of
management should be to obtain and sustain complete control.
Unfortunately, studies found that most patients are actually poorly
controlled.
Patient education:
Patients should be educated about the nature of their illness and its
symptoms, the difference between various medications, the
technique of inhaler use, and the use of PEF as a guide to severity
and subsequent management. Whenever possible, patients should
take responsibility in managing themselves. Written action plans
are useful.
Avoidance of aggravating factors:
This is most successful in patients with occupational asthma. To a
lesser extent, removal of a household pet from homes can improve
asthma caused by animal dander allergy. It is less successful for
house dust mite. Cockroaches and fungi have been noticed to be
important sources of allergy and should be sought. Smoking -

-
cessation is particularly important. Smoking increases sensitization
-

and induces corticosteroid resistance in the airways

Drug therapy:
A stepwise approach is followed in the drug therapy of asthma
Step 1: Regular preventer (controller) > Low ICS

The initial therapy for a patient diagnosed with asthma would be a

low dose inhaled glucocorticoid (ICS). For adults, a starting dose
equivalent to beclometasone dipropionate (BDP) 500 μg per day is
-

reasonable. Short-acting β2 agonists are used as required to control

symptoms.

7
 -> Long acting Bagonist-

session
-
2 Buonasilarin
A variety of different inhaled devices are available and the choice of
device should be guided by patient preference and competence in its
use.
Step 2: Initial add-on therapy
If asthma remains poorly controlled despite regular preventer
therapy, the next step should be addition of a long-acting beta
agonist (LABA).
This should be done via a combination ICS/LABA inhaler to prevent - -

inadvertent administration of LABA monotherapy and risk of

-

asthma death. Short-acting β2 agonists are still used as required to

relieve symptoms. 5.5, s
-

81
-

(chr)
Lung acting
-> - s
-
+

-> fast acting. >

12hr Combination ICS/formoterol inhalers (containing the fast-acting

Salmeterol <
=>
- - -

* 5 5
LABA “formoterol” rather than other LABAs) can be used as a
-

·
maintenance and reliever (MART) inhaler allowing for auto-
- >

titration of therapy in response to symptoms (using the same

- -

inhaler as controller and reliever)

Step 3: Additional add-on therapies medium ICSLABA
- -

- >

If the patient is still symptomatic, a review of his adherence to

treatment and the technique of inhaler use are essential. Attention
should be focused on the presence of co-morbidities that can
aggravate asthma (like gastro-oesophageal reflux disease and
rhinosinusitis). =], 1-= 19

There are a number of options to consider at this stage:

·  The ICS dose can be increased to a medium dose (1000 ug
-

BDP) (the preferred option)

 A trail of adding a leukotriene antagonist (LTRA) (oral
montelukast)
 A trial of adding a slow-release theophylline Long acting
->
musca.....
antagonist.
Step 4: High-dose therapies > High ICS +
LAMA

In adults, a trial of high dose inhaled glucocorticoid (2000 μg BDP)

should be started. Trials of LTRA, long-acting antimuscarinic agents
(LAMA) like tiotropium, theophyllines or a slow-release oral β2-
-

agonist may be considered.

If the trial of add-on therapy is ineffective, it should be discontinued.
- -
-

LA ~A+ aeastdium ICS->; $i2;/LAMA,,;b

E
->
10 8 medium is
15; ss sobisss, .ICS
high dose
-
 Step 5: Continuous or frequent use of oral glucocorticoids
At this stage, oral prednisolone (usually administered as a single
daily dose in the morning) should be prescribed at the lowest dose
- -

necessary to control symptoms and the patients should be referred

for specialist severe asthma assessment.
These patients should be considered for biologic therapy to
minimise long-term harm from oral glucocorticoids.
Omalizumab (anti-IgE) therapy may be considered for those
-

patients with severe IgE-driven atopic asthma. Benralizumab (anti-

IL5r), mepolizumab (anti-IL5), reslizumab (anti-IL5) or dupiliumab
(anti-IL4/13) could be considered for patients with eosinophilic
forms of asthma.
Assessment of asthma control:
In each follow up visit (every 3-6 months), patient control should be
assessed using a validated scoring system like “asthma control test"
(ACT) and spirometry. Treatment is stepped up if control is not
achieved.
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formoterol. 24 I

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zj Once control is achieved and maintained for at least 3 months, ICS

-50
is reduced in a stepdown approach keeping the smallest dose
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-

sufficient to maintain effective control.

j161 -

Asthma in pregnancy:
Step 3
I! j  Well-controlled asthmatics have good pregnancy outcome.
Step 9  Pregnancy in women with less-controlled asthma may cause
=

& Si-
more severe symptoms and poor maternal and fetal outcome.
 All drugs including oral prednisolone are safe.
-

LABA
⑲1eix  Prostaglandin F2α is bronchoconstrictor and should not be
>
StepI I3 used to induce labour.
-
-

-slots.- 22:
- 14/ss!
--
is 9 step-S. Step is
--55
·
$,jisafe's
city's Prednisolones y I., exacerbar 14Is,loss's s
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  Women on maintenance prednisolone >7.5 mg/day should
receive hydrocortisone 100 mg 3–4 times daily during labour.
 Breast feeding should continue.
-
-

 Uncontrolled asthma represents the greatest danger to the

- -

mother and foetus.

u n
-

Acute exacerbation of asthma:

Mild to moderate exacerbation
Patients should be educated about features of mild to moderate
exacerbation, which include:
-
1. Progressively worsening PEF records (or fall of PEF below
-

60% of best personal records)

-

2. Onset of nocturnal asthma

Poor
controlled 3. Persistence of morning dipping to midday
- >

4. Diminished response to bronchodilators -

5. Symptoms requiring nebulized therapy ->

15 C
Patients can be taught to start a short "rescue" course of oral
I corticosteroid (prednisolone 30 -60 mg daily is adequate). No need
- -

to taper the dose if used for less than 3 weeks.

Severe exacerbations
Severe exacerbations (also called acute severe asthma) should be
-

treated in hospital. During these exacerbations, the patient gets

severe dyspnoea, with tachypnoea (RR > 25/min), tachycardia (PR
> 110/min), and is unable to complete a sentence in one breath. PEF
is 33%-50% of predicted (generally less than 200 L/min). PaO2 (or
SpO2) is usually normal, but PaCO2 is low (CO2 washed out by
hyperventilation).
In more severe life threatening exacerbation, the patient may be
unable to speak, is cyanosed, exhausted, and confused. There may
tens
be bradycardia, silent chest and coma may follow. PEF is less than
33% predicted (less than 100 L/min) or unrecordable. SpO2: <92%
- (PaO2 <60 mmHg). PaCO2: normal or raised.

blood 99

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igpios Brady II
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~5 Asthmal is
hyperventilations is Tacy 11s
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high -

The assessment of patients with severe asthma exacerbations (acute

severe asthma) is made principally on clinical findings.
Measurement of PEF is mandatory, unless the patient is too ill to
cooperate.
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
Severe exacerbations (acute severe asthma and life threatening
asthma) are treated in hospital as an emergency:
 Oxygen: Controlled supplemental oxygen should be
administered to maintain SaO2 94%–98%. The presence of a protemia
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. corticosteroid
 High doses of inhaled bronchodilators: Short-acting β2-
Sabatan
mm of choice. They can be administered
agonists are the agent

Systemic steroid
11
 either via multiple doses of a metered-dose inhaler via a
SAMA
spacer device, or via a nebulizer (5 mg salbutamol solution)
2
-
- driven by oxygen. Ipratropium bromide provides further
=

bronchodilator therapy and should be added if there is a

failure to respond to salbutamol or in life-threatening attacks.
Inhaled bronchodilators can be repeated after 30 minutes if
the response is inadequate, then hourly until improvement.
 Systemic corticosteroids: They should be administered to all
-

patients with an acute severe attack. They can usually be

administered orally as prednisolone (40 mg) but intravenous
hydrocortisone (200 mg) may be used.
If patients fail to improve, a number of further options may be
considered, including intravenous magnesium and intravenous
aminophylline (but cardiac and therapeutic drug level monitoring is
recommended).
PEF should be recorded regularly and pulse oximetry should be
monitored to ensure that SaO2 94%–98% is maintained. Repeat
arterial blood gases are necessary if the initial PaCO2 measurements
were normal or raised, the PaO2 was below 60 mmHg or the
- - -

patient deteriorates.
Ventilatory support (endotracheal intubation and mechanical
ventilation) is needed if life threatening asthma persists despite
adequate therapy. Indications include coma, respiratory arrest,
extreme exhaustion and deterioration of blood gas results.
The patient is discharged when he is stable (nebulised therapy
should have been discontinued for at least 24 hours) with PEF more
than 75% predicted. Short course of oral corticosteroids should be
prescribed with optimization of his medication (consider stepping
up) and managing any possible trigger factors.
The outcome of acute severe asthma is generally good; death is rare.
- --
>

Failure to recognize the severity of an attack contributes to under-

treatment or treatment delay.
· Seere
J1s, 3 Jei
10/2023 -36555.1:lib

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-

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>

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