Bronchial Asthma

General Considerations:
Bronchial asthma is a disease of diffuse airway inflammation caused by a variety of
triggering stimuli resulting in partially or completely reversible bronchoconstriction.

Asthma triggers

• Viral respiratory infections

• Cold air
• Environmental allergens and/or irritants
• Exercise; usually at termination of exercise
• Abrupt changes in weather
• Emotional stress
• Drugs (aspirin, other non-steroidal anti-inflammatory drugs, beta-blockers)
• Gastroesophageal reflux disease

Pathophysiology
Asthma involves:
• Bronchoconstriction;
• Airway edema and inflammation;
• Airway hyperreactivity;
• Airway remodeling.
Atopic, or "extrinsic," asthma has been thought to result from sensitization of the
bronchial mucosa by tissue-specific antibodies. The antibodies produced are
specificimmunoglobulins of the IgE (type I) class, and the total
serum IgE concentration is usually elevated. Exposure to the appropriate allergens
by inhalation results in an antigen-antibody reaction,
that releases vasoactive bronchoconstrictive chemical mediators, causing the
characteristic tissue changes.

Classification

Classification of severity of chronic stable asthma

Symptoms Nocturnal Lung function
symptoms
 Mild intermittent ≤ 2 times / week ≤ 2 times / month FEV1 ≥ 80 %
predicted
Mild persistent > 2 times / week > 2 times / month FEV1 ≥ 80 %
but < 1 / day predicted
Moderate daily symptoms > 1 time / week FEV1 60-80 %
persistent predicted
Severe persistent continual Frequent FEV1 ≤ 60 %
symptoms predicted

Adapted from National Asthma Education and Prevention Program. Guidelines for the
diagnosis and management of asthma, 2011.

Classification of severity of asthma exacerbations

Mild Moderate Severe Impending
respiratory failure

Symptoms:breathlessne
ss
With With At rest At rest
activity talking

Speech sentences phrases words Mute

Signs:
body position Able to recline Prefers Unable to recline Unable to recline
sitting

Respiratory rate Increased increased Often > 30/min > 30/min

Use of accessory Usually not commonl usually Paradoxical

muscles y movement

Breath sounds Moderate mid- Loud Loud inspiratory an Little air

to end- expirator d expiratory movement without
expiratory y wheezes wheezes
wheezes wheezes

Heart rate (beats/min) < 100 100-120 > 120 Relative bradycardi
a

Pulsus paradoxus(mm < 10 10-25 Often > 25 Often absent

Hg)

Mental status May be agitated Usually Usually agitated Confused/drowsy

agitated

Functional
assessment PEF (%
predicted) > 80 50-80 < 50 < 50
 SaO2 (%) > 95 91-95 < 91 < 91

PaO2 (mm Hg) Normal > 60 < 60 < 60

PaCO2 (mm Hg) < 42 < 42 ≥ 42 ≥ 42

Adapted from National Asthma Education and Prevention Program. Guidelines for the diagnosis
and management of asthma, 2011.

Essentials of Diagnosis:
• Recurrent acute attacks of dyspnea, cough, and mucoid sputum, usually
accompanied by wheezing.
• Prolonged expiration with generalized wheezing and musical rales.
• Bronchial obstruction reversible by drugs

Clinical presentation
Presence of any of these signs and symptoms should increase the suspicion of
asthma:
 Wheezing high-pitched whistling sounds when breathing out — especially in
children (a normal chest examination does not exclude asthma).
 History of any of the following:
 Cough, worse particularly at night
 Recurrent wheeze
 Recurrent difficult breathing
 Recurrent chest tightness
 Symptoms occur or worsen at night, awakening the patient.
 Symptoms occur or worsen in a seasonal pattern.
 The patient also has eczema, hay fever, or a family history of asthma or atopic
diseases.
 Symptoms occur or worsen in the presence of:
 Animals with fur
 Aerosol chemicals
 Changes in temperature
 Domestic dust mites
 Drugs (aspirin, beta blockers)
 Exercise
 Pollen
 Respiratory (viral) infections
 Smoke
 Strong emotional expression
 Symptoms respond to anti-asthma therapy
 Patients colds "go to the chest" or take more than 10 days to clear up
Methods of investigation

 Spirometry
 Flow-volume loops
 Provocative testing
 DLco testing
 Chest x-ray
 Allergy testing
 Blood analysis
 Sputum evaluation.
 Peak expiratory flow

Diagnostic challenges
 Cough-variant asthma.
 Exercise-induced bronchoconstriction.
 Children 5 Years and younger.
 Asthma in the elderly.
 Occupational asthma.

Differential diagnosis of bronchial asthma

 COPD
 Bronchial tumor
 Angioedema
 Bronchiectasis
 Vocal cord paralysis
 Hysteria
 Foreign body aspiration

Treatment

Medications used to treat asthma are generally divided into 2 main categories:
relievers and controllers. Relievers are best represented by the inhaled short-
acting β2-agonists. These quick-acting bronchodilators are used to relieve
acute intercurrent asthma symptoms, only on demand and at the minimum required
dose and frequency.
 Stepwise approach for treatment of asthma
Long-term control Quick-relief

Step 1: Mild No daily medication needed Short-acting bronchodilator: β2-

intermittent agonist when needed

Step 2: Mild One daily medication: inhaled corticosteroid Short-acting β2-agonist when
persistent (low dose) or mast cell needed
stabilizer, leukotriene receptor
antagonist, theophylline

Step 3: Moderate Daily medication: inhaled corticosteroid Short-acting β2-agonist when

persistent (medium dose) and/or long-acting inhaled β2- needed
agonist orleukotriene receptor
antagonist, theophylline

Step 4: Severe Daily medication: inhaled corticosteroid (high Short-acting β2-agonist when
persistent dose) and long-acting inhaled β2-agonist, needed
sustained-release theophylline. Corticosteroid
tablets (usually less than 60 mg/d)

Step down: Review treatment every 1-6 months; a gradual stepwise reduction in treatment
may be possible.

Step up: If asthma control is not maintained, consider step up to next treatment level after
reviewing medication technique, adherence and environmental control

Adapted from National Asthma Education and Prevention Program. Guidelines for the diagnosis
and management of asthma, 2011.

Long-term control medications for asthma

Drug Important Usual Side effects
formulations adult
dosage

Inhaled 80 µg/puff; 200 One to two High daily doses may be

corticosteroidsBeclomethasone dipropionate puffs/inhaler puffs BID associated with skin thinning
and bruises, and rarely - with
Budesonide (PulmicortTurbuhaler) Dry powder delivery One adrenal suppression. Local
system: 200 µg/puff; inhalation side effects are hoarseness
200 puffs/inhaler twice a and oropharyngealcandidiasis.
day

Fluticasone (Flovent) 220 µg/puff; 120 Two or

puffs/inhaler three puffs
twice a
day

Triamcinolone acetonide(Azmacort) 100 µg/puff; 240 Two or

puffs/inhaler three puffs
four times
a day

Systemic corticosteroidsMethylprednisolone Tablets 4 mg 5-60 mg Osteoporosis, hypertension,

daily to diabetes, cataracts, adrenal
 every other suppression, growth
day as suppression, immune
needed suppression, stomach ulcer,
obesity, skin thinning or
Prednisolone Tablets 1, 2.5, 5, 10, 5-60 mg muscle weakness.
20, 50 mg daily to
every other
day as
needed

Combination: Inhaled corticosteroid and Dry powder delivery One puff Side effects of inhaled
long-actingβ2-agonist - system: 100, 250 or twice a corticosteroid and/or long-
Fluticasone andsalmeterol (Advair Diskus) 500 µg fluticasoneper day of acting β2-agonist (see certain
dose and 50 250/50 medicines) are less
µg salmeterolper dose prominent.

Cromolyn (Intal) 800 µg per puff: 200 Two-four Minimal side effects. Cough
puffs/inhaler puffs four may occur upon inhalation.
times a
day

Nedocromil sodium 1,75 mg/puff; 112 Two puffs

puffs/inhaler four times
a day

Long-acting β2-agonists Salmeterol (Serevent) 21 µg/puff: 120 Two puffs Tachycardia, anxiety, skeletal
puffs/inhaler every 12 muscle tremor,
hours headache, hypokalemia.

Methylxanthines Sustained-release Initially Nausea and vomiting,

Theophylline tablets and capsules 10mg/kg/d seizures, tachycardia,
up to 300 arrhythmias.
mg
maximum;
then 200-
600 mg
every 8-24
hours

Leukotriene modifiers Montelukast (Singulair) Tablet 10 mg One tablet Elevation of liver

each enzymes,hyperbilirubinemia,
evening reversible hepatitis.

Zileuton (Zyflo) Tablet 600 mg One tablet

four times
a day

Immunomodulators: Dose administered Every 2-4 Pain and bruising at injection

Omalizumab subcutaneously weeks site and very rarely
Anti-IgE depending on weight anaphylaxis.
and IgE concentration

Adapted from National Asthma Education and Prevention Program. Guidelines for the diagnosis
and management of asthma, 2011.
Inhaled ipratropium bromide is less effective, but is occasionally used as a reliever
medication in patients intolerant of short-acting β2-agonists. Controllers (or
preventers) include anti-inflammatory medications, such as inhaled (and
oral) glucocorticosteroids, leukotriene-receptor antagonists, and anti-allergic or
inhaled nonsteroidal agents, such ascromoglycate and nedocromil. These agents
are generally taken regularly to control asthma and prevent exacerbations. Inhaled
glucocorticosteroids are the most effective agents in this category.
The controller group also includes some bronchodilators that are taken regularly in
addition to inhaled glucocorticosteroids to help achieve and maintain asthma control.
These include the long-acting inhaled β2-agonists salmeterol and formoterol, which
are the first choice in this category, as well as theophylline and ipratropium. The β2-
agonists andipratropium are considered of no significant benefit in reducing airway
inflammation.

Management approach based on control

Level of Control Treatment Action

Maintain and find lowest

Controlled
controlling step

Consider stepping up to gain

control

Partly controlled
Uncontrolled Step up until controlled

Exacerbation Treat as exacerbation

Treatment Steps
 Step1 Step 2 Step 3 Step 4 Step 5
Asthma education. Environmental control.
(If step-up treatment is being considered for poor symptom control, first check inhaler technique,
check adherence and confirm symptoms are due to asthma).
As
needed
rapid-
As needed rapid-acting β2-agonist
acting β
2-
agonist
To Step 4
To Step 3 treatment,
Select one Select one treatment, add
select one or more
either
Medium-or high-
Low- Oral glucocortic
Low-dose ICS pluslong- doseICS plus long-
dose inhaled osteroid
acting β2-agonist acting
Control ICS* (lowest dose)
β2-agonist
ler
Medium-or high-doseICS
options Leukotriene modifier
*** Leukotrienemo Anti-
Low-dose
difier* Sustained releasetheo IgE treatment
ICS plusleukotriene modifi
phylline
er
Low-dose
ICS plussustained releaset
heophylline
*ICS = inhaled glucocorticosteroids
** = Receptor antagonist or synthesis inhibitors
*** = Recommended treatment (shaded boxes) based on group mean data. Individual
patient needs, preferences, and circumstances (including costs) should be considered.
2

Alternative reliever treatments include inhaled anticholinergics, short-acting oral β2-

agonists, some long-acting β-agonists, and short-acting theophylline. Regular dosing
with short and long-acting β2-agonists is not advised unless accompanied by regular use
of an inhaled glucocorticorsteroid.

There is some evidence that theophylline may have immunomodulatory effects, but
the clinical significance of this remains to be demonstrated. Asthma drugs
are preferably inhaled, because this route minimizes systemic absorption and, thus,
improves the ratio of the therapeutic benefit to the potential side-effects. The patient
must have repeated instruction on how to use the inhaled medication. The recently
developed oral leukotriene-receptor antagonists have good safety and tolerance
profiles and are taken orally, which may help certain patients comply with treatment.
Asthma medications should be used at the minimum dose and frequency required to
maintain acceptable asthma control; they should not be used as a substitute
for proper control of the environment. Asthma medications are considered to be safe
over many years when used appropriately. The participants in the asthma consensus
conference have reviewed the role of each category of medication. In the following
sections they describe briefly the mode of action, pharmacologic and clinical
profile, mode of administration and potential side-effects of these drugs. The
treatment may be divided into 2 phases: treatment of the acute attack
and interim therapy, which is aimed at preventing further attacks.

Levels of asthma control

A. Assessment of current clinical control (preferably over 4 weeks)
Characteristics Controlled Partly controlled Uncontrolled
(all of the (any measure
following) presented)
Daytime symptoms None (twice or More than twice/week Three or more
less/week) features of partly
Limitation of activities None Any controlled asthma*†
Nocturnal None Any
symptoms/awaking
Need for reliever/ None (twice or More than twice/week
Rescue inhaler less/week)
Lung function (PEF or Normal <80% predicted or
FEV1) personal best (if known)
B. Assessment of future risk (risk of exacerbations, instability, rapid decline in lung function,
side effects)
Features that are associated with increased risk of adverse events in the future include:
1

Poor clinical control, frequent exacerbations in past year*, ever admission to critical care for
asthma, low FEV, exposure to cigarette smoke, high dose medications
*Any exacerbation should prompt review of
maintenance treatment to ensure that it is adequate
†By definition, an exacerbation in any week makes that an uncontrolled asthma week

Deterrence/Prevention
 Another essential component in the treatment of asthma is the control of
factors contributing to asthma severity.
 Exposure to irritants or allergens has been shown to increase asthma symptoms
and cause exacerbations. Clinicians should evaluate patients with persistent
asthma for allergen exposures and sensitivity to seasonal allergens. Skin testing
results should be used to assess sensitivity to perennial indoor allergens, and
any positive results should be evaluated in the context of the patient's medical
history.
 All patients with asthma should be advised to avoid exposure to allergens to
which they are sensitive, especially in the setting of occupational
asthma. Other factors mayinclude the following:
·
o Environmental tobacco smoke
 o Exertion during high levels of air pollution
o Use of beta-blockers
o Avoidance of aspirin and other nonsteroidal anti-inflammatory drugs if
the patient is sensitive
o Avoidance of sulfites or other food items/additives to which the patient
may be sensitive
o Occupational exposures

Complications
 The most common complications of asthma include
pneumonia, pneumothorax or pneumomediastinum, and respiratory failure
requiring intubation in severe exacerbations.

 Risk factors for death from asthma include the following:

·
o Past history of sudden severe exacerbations, history of prior intubation,
or ICU admission
o Two or more hospitalizations or 3 or more emergency department visits
in the past year; hospitalization or emergency department visit in the
past month
o Use of more than 2 short-acting beta-agonist canisters per month
o Current use of systemic corticosteroids or recent taper
o Comorbidity from cardiovascular disease
o Psychosocial, psychiatric, or illicit drug use problems
o Low socioeconomic status or urban residence
 Complications associated with most medications used for asthma are relatively
rare. However, in those patients requiring long-term corticosteroid use,
complications may include osteoporosis, immunosuppression,
cataracts, myopathy, weight gain, addisonian crisis, thinning of skin, easy
bruising, avascular necrosis, diabetes, and psychiatric disorders.

Prognosis
 Approximately half the children diagnosed with asthma in childhood outgrow
their disease by late adolescence or early adulthood and require no further
treatment.
 Patients with poorly controlled asthma develop long-term changes over
time, ie, with airway remodeling. This can lead to chronic symptoms and a
significant irreversible component to their disease.
 Many patients who develop asthma at an older age also tend to have chronic
symptoms.
Patient Education
o Integrate patient education into every aspect of asthma care.
o All members of the health care team, including nurses, pharmacists, and
respiratory therapists, provide education.
o Clinicians teach patients asthma self-management based on basic asthma
facts, self-monitoring techniques, the role of medications, inhaler use,
and environmental control measures.
o Develop treatment goals for the patient and family.
o Develop a written, individualized, daily self-management plan.
o Encourage adherence by the patient.