- Asthma is s syndrome characterized by airflow obstruction.
- There is airway narrowing with consequent reduced airflow and
symptomatic wheezing and dyspnea.
- Most of the patient are atopic, with allergic sensitization
to the house dust mite Dermatophagoides pteronyssinus.
- ASTHMA CAN PRESENT AT ANY AGE, with a peak age of 3 years
Ø RISK
FACTORS AND TRIGGERS:
Asthma is a heterogeneous disease that has genetic as well as
environmental factors.
- Atopy: Patient with Asthma commonly suffer from other
Atopic disease like allergic rhinitis and atopic dermatitis (eczema).
- Genetic Predisposition: Asthma is Polygenic. Most
consistent findings have been associations with polymorphisms of genes on
chromosome 5q.
Novel gene associated with asthma: ADAM-33, DPP-10 and
ORMDL3.
- Infections: Commonly Rhinovirus, atypical bacteria
like Mycoplasma and Chlamydophilia.
“Hygiene Hypothesis”: Lack of infections in early
childhood preserves the Th2 cell bias at birth. Exposure to infections and endotoxin
results in a shift towards a predominant protective Th1 immune response. So, children
brought up on farms who are exposed to a high level of endotoxin are less
likely to develop allergic sensitization than children raised on dairy farms.
- Diet, Air Pollution, Occupational exposures, Obesity (BMI>30
kg/m2).
- Intrinsic Asthma: Patients with intrinsic asthma have negative
skin tests to common inhaled allergens and normal concentrations of IgE. Commonly
associated with nasal polyps, and maybe Aspirin sensitive.
- Pharmacologic agents: All beta-blockers (even
selective or topical Beta Blockers). Aspirin may worsen asthma in some
patients.
- Exercise-induced asthma: Typically begins after
exercise and recovers within 30 minutes.
Ø DIAGNOSIS:
Spirometry: Reduced FEV1, FEV1/FVC ratio and PEF.
Reversibility: >12% and 200mL increase in FEV1 15
minutes after an inhaled short-acting Beta2 agonist (SABA).
-
Total serum IgE and specific IgE to inhaled allergens.
- Chest Xray: Usually normal or hyperinflated lungs. In exacerbations,
there may be evidence of pneumothorax.
- Skin tests: It is positive in allergic asthma and negative
intrinsic asthma.
- Exhaled Nitrous Oxide: Elevated levels are reduced by
Inhalational Corticosteroid therapy, May be useful to test compliance with
therapy.
- ABG analysis: Hypoxaemia and Hypocarbia during acute
attack. In severe acute asthma,
hypercarbia develops.
Ø TREATMENT:
I.
Bronchodilator therapies.
II.
Controller therapies.
III.
Management of Chronic Asthma.
I. Bronchonchodilator therapies:
a. Beta2
agonists:
§ Primary action: relaxes smooth muscle cells of
all airways.
§ Has additional
non-bronchodilator effects, including mast cell inhibition, reduction in plasma exudation,
etc.
§ Used as
Inhalers – because of its rapid actions used for acute exacerbations (relievers).
§ Increased use
of SABA (e.g.: albuterol and terbutaline) indicates poorly controlled asthma.
§ LABA (Long
acting B2 agonists) e.g. Salmeterol and formeterol, can be given twice daily.
§ LABA should
NOT be given in absence of Inhalational Corticosteroid (ICS) therapy as they do
not control underlying inflammation.
§ Side
effect: Tremors and palpitations.
b. Anticholinergics:
§ Long-acting
Muscarinic agonists (LAMA) like tiotropium bromide may be used as an
additional bronchodilator when controlled is not achieved by ICS-LABA combination.
§ These are
less effective than Beta-agonists.
§ Side
effects: Dry mouth, urinary retention, and glaucoma.
c. Theophylline:
§ Inhibits
Phosphodiesterases in airway smooth muscle cells, which increases cAMP.
§ It
activates histone deacetylase-2 (HDAC2) – Switches off activated inflammatory
genes.
§ Can be
given orally or IV route.
§ Required
plasma therapeutic concentration: 10-20 mg/L.
§ Side
effects: Nausea, Vomiting headaches, palpitations, diuresis and at high
concentrations can cause arrhythmias and seizures.
II. Controller therapies:
a. Inhaled corticosteroids:
§ Most
effective controllers.
§ They are
NOT bronchodilators but they relieve or prevent airflow obstruction by their
anti-inflammatory effect and decrease bronchial hyperresponsiveness.
§ Usually given
twice daily.
§ Now given
as first-line therapy for patients with persistent asthma.
b. Systemic
corticosteroids:
§ IV route (like
hydrocortisone or methylprednisolone) is used for acute severe asthma.
§ Oral
steroids (Prednisolone 30-45 mg once daily for 5-10 days) to treat acute
exacerbation can be used; no tapering is needed.
§ Intramuscular
Triamcinolone acetonide can be used occasionally in non-compliant patients.
c. Antileukotrienes:
§ E.g.:
Montelukast, Zafirlukast.
§ Used in
patient who require high dose of steroid therapy.
d. Cromones:
§ E.g. Sodium
Chromoglycate.
§ It inhibits
degranulation of mast cells.
§ Only used
as prophylactic treatment of Asthma.
e. Steroid
sparing therapies:
§ Can be used
in patients who have serious side effects from steroid therapy.
§ E.g.:
Methotrexate, cyclosporine A, Azathioprine, etc.
f. Anti-IgE:
§ Omalizumab.
§ Route: Subcutaneous,
every 2-4 weeks.
III. Management of Chronic Asthma:
§ Stepwise
therapy:
- Step 1: Prefer SABA as required for symptom relief.
- Step 2: Prefer low dose ICS to be given twice daily.
- Step 3: If not controlled, add LABA (use of combination
inhaler).
- Step 4: If not controlled, use High dose ICS with LABA.
- Step 5: I not controlled, add OCS therapy along with LABA +
ICS.
