Asthma

Definition
• Asthma is a chronic inflammatory disorder of the airways
associated with airway hyperresponsiveness causing variable
airway obstruction, that reversible spontaneously or with
treatment.
• Leading to recurrent episodes of wheezing, breathlessness,
chest tightness and cough.

Epidemiology
• Common disease 15%-20% in developed countries, 2%-4% in
developing countries
• One of the most common and important long-term respiratory
conditions in terms of global years lived with disability
• Affects all ages, more common in children
• In childhood asthma M>F, puberty 1:1, adult onset asthma F>M
• Increased over the past decades

Pathophysiology
• A complex interaction of cells and mediators that leads to:
1. Inflammation of the airways
2. Airway hyperresponsiveness
3. Airflow limitation (obstruction), which is usually variable and
reversible

Inflammation

• Cells involved:
- Mast cells, eosinophils, basophils and macrophages
- Epithelial cells, goblet cells, smooth muscles, endothelial cells and
myofibroblasts
• Mediators involved:
- Histamine, platelet activating factors, PGs (D2,D4,E4,C4), IL(5,13)
- IgE
- Leukotrienes

Hyperresponsiveness
• the tendency for airways to narrow excessively in response to triggers
that have little or no effect in normal individuals

Air flow limitation
• Defined as decreased FEV1/FVC ratio< 70% ??????
• In asthma this limitation is usually reversible
• Caused by :
- Bronchoconstriction (smooth muscle contraction)
- wall edema (increased permeability of vessels)
- increased secretions (goblet cells)

• With increasing severity and chronicity of the disease, remodelling of
the airway may occur, leading to:
- Fibrosis of the airway wall increasing the thickness of the epithelial
basement membrane
- Hypertrophy and hyperplasia of smooth muscles
- Hyperplasia of goblet cells and loss of cilia on epithelial cells
This will cause fixed narrowing of the airway and a reduced response to
bronchodilator medication

• Triggers
- house dust mites
- Cockroaches and other insect debries
- Cat dander
- Seasonal pollens
- Products of combustion
- Tobacco
- Respiratory infections

- NSAID’s and aspirin, beta blockers
- Stress including exercise (exercise induced asthma)
- Post nasal drip, GERD, aspiration

Risk factors
• Genetic factors
Atopy, high IgE levels
• Environmental factors
Indoor and outdoor air pollution, allergens
• Infections
Viral infections, atypical bacterial infections
• Obesity
• Race and gender

Clinical features
• Typical symptoms include recurrent episodes of wheezing, chest
tightness, breathlessness and cough
• These symptoms tend to be provoked by exposure to triggers
• More prominent in the night and early morning

• Signs on physical exam
- Normal exam in-between the attacks, but some findings that increase
the probability of asthma: eczema, nasal polyps
- Tachycardia and tachypnea
- Prolonged expiratory phase with or without diffuse wheeze
- Use of accessory muscles
- Pulsus paradoxus

Differential diagnosis
• Vocal cord dysfunction
• Cardiac asthma
• COPD
• Upper air way obstruction
• Other conditions: anemia, obesity, LV dysfunction, bronchiectasis

Laboratory investigations
• Lung function tests
- Peak expiratory flow
Simple, cheap, can be used at home or work for assessing diurnal
changes or relation to occupational allergens (occupational asthma)
- Spirometry with bronchodilator reversibility
FEV1, FVC, ratio (FEV1/FVC)
- Bronchial challenge test
Used rarely in case of diagnosis uncertainty

• Blood tests
- CBC for eosinophil count
- IgE level
- radioallergosorbent testing (RAST)
to identify if the serum has IgE specific certain allergens
- ABG
in acute exacerbations

• Chest imaging
- Chest radiograph
Usually normal in mild to moderate asthma
Hyperinflation maybe seen in more severe asthmatic patients
Useful in case of acute exacerbations to exclude pneumothorax,
pneumonia or other diagnoses
- Chest CT
To detect bronchiectasis in allergic bronchopulmonary aspergillosis
(ABPA)

• Exhaled nitric oxide (FeNO)
- Not widely available
- Exhaled nitric oxide is high due to eosinophilic inflammation of the
airways
- Can be useful in pediatric patients or for assessment of adherence to
medications
- Still not recommended by the guidelines

• Skin prick test

Diagnosis

Management
• Goals of asthma treatment
1. Achieve and maintain control of symptoms.
2. Maintain normal activity levels, including exercise.
3. Maintain pulmonary function as close to normal levels as possible.
4. Prevent asthma exacerbations.
5. Avoid adverse effects from asthma medications.
6. Prevent asthma mortality.

Management
1. Patient education.****
2. Identify and reduce exposure to risk factors, including cigarette
smoking. (this includes pneumococcal vaccination (Pneumovax 23) and
annual influenza vaccinations)
3. Pharmacological therapy as a stepwise approach.

Stepwise approach

1. Inhaled corticosteroids (ICS)
- Beclomethasone, budesonide, mometasone, ciclesonide and
fluticasone are the common ICSs in clinical use .
- Decreases the inflammatory process in the airways with negligible
systemic adverse effects in recommended doses.
- Common side effects oral candidiasis, dysphonia.
- Rarely in high doses, systemic side effects of steroids might be seen

2. Short acting beta2 agonists (SABA)
- Salbutamol, terbutaline
- Cause smooth muscle relaxation, resulting bronchodilation
- Side effects includes tachycardia, arrhythmia, fine tremor, sweating
and agitation
- IV and oral forms

3. Long acting beta2 agonists (LABA)
- As Salmeterol and Formoterol.
- Duration of action is more than 12 hrs.
- In asthma treatment, should be used as add-on therapy to ICS

4. Short acting muscarinic antagonists (SAMA)
- As Ipratropium
- Decreases mucus secretions and causes smooth muscle relaxation
and bronchodilation by blocking the nervous stimuli provided by the
vagal nerve.
- Less effective than SABA in treating asthma, used more in COPD.
- Used in combination with SABA for stronger effect.

5. Long acting muscarinic antagonists (LAMA)
- As tiotropium (the only one approved for asthma), aclidinium,
glycopyrronium, umeclidinium

6. Leukotriene modifiers
- as Montelukast, Zafirlukast.
- Side effects : headache, rashes, and in rare cases eosinophilic
granulomatosis with polyangiitis (Churg-Strauss)

7. Methylxanthines
- As Theophylline, Aminophylline
- Relaxes the smooth muscles and decreases histamine secretion by
mast cells, which leads to bronchodilation.
- Has a narrow therapeutic window
- Side effects: agitation, tachycardia, arrhythmias, GI upset and
vomiting.

8. Systemic steroids
- Used in severe, chronic, poorly controlled cases.
- Also used in exacerbations, so it will take effect after hours i.e. it will
take effect during the late phase.
- Long term use will cause side effects.
- The least dose needed to control the symptoms is used.

9. Mast cell stabilizers (cromones)
- Cromolyn and nedocromil
- Less effective, expensive, not widely used

10. Monoclonal antibodies
- Very expansive, indicated in selected groups of uncontrolled
asthmatics
- Omalizumab : anti IgE
- Mepolizumab : anti IL-5
- Reslizumab: anti IL-5
- Benralizumab: anti IL-5 receptor
- Dupilumab: anti IL-4 & IL-3

11. Immunotherapy
- Greatest benefit seen in patients with single specific allergic trigger
- Allergen specific immunotherapy (ASIT): repeated administration of
allergen products under medical supervision
- Side effects :anaphylaxis

Asthma Exacerbation
• Usually triggered by viral respiratory infections, but exposure to other
triggers can precipitate an exacerbation
• Most attacks develop over several hours, but in some attacks
deterioration occurs suddenly (brittle asthma)
• Assessing severity is the cornerstone of managing an asthma
exacerbation

• Mild asthma exacerbation:
- Many respond to high dose of inhaled SABA
- If no response start ICS (if not on ICS), or give short course systemic
steroids (7 days) starts in ED
- Early follow up visit to clinic

• Moderate asthma exacerbation:
- Correct hypoxemia with oxygen
- Many respond to high dose of inhaled/nebulized (SABA/SAMA)
- Add ICS (if not on ICS)
- Short course systemic steroids (7 days) starts in ED
- If respond, discharge with early clinic visit
- If no response consider admission to floor

• Severe (life threatening) asthma exacerbation:
- Oxygen therapy targeting SpO2>90%
- High dose SABA/SAMA
- Systemic steroids (oral or intravenous)
- Magnesium sulfate
- Admission to intensive care unit for close observation
- Antibiotics are not indicated unless high likelihood of bacterial
pneumonia (fever, purulent sputum)

• Impending respiratory failure
- Due to worsening obstruction and muscle fatigue
- Endotracheal intubation and mechanical ventilation