Asthma

Common chronic inflammation condition of lower respiratory tract.

Increasing prevelance, especially in second decade of life.
10-15% population affected
More common in developed countries.

Definition:
Classification
Extrinsic (atopic)
Allergens (common inhaled allergens, e.g. dust mite, pollen and fungi)
identified by skin-prick reactions.
In adults sensitisation to chemicals or biological products may be the
cause.
Intrinsic
Usually starts in middle age; no definite external cause identifiable.
Many patients show degree of atopy and gives history consistent with
childhood asthma.
Aetiology:
1. Atopy
Develop IgE antibodies against common environmental antigens.
Serum IgE affected by environmental and genetic factors.
Growing up in relatively clean environment may predispose towards IgE
response to allergens.
2. Hyperresponsiveness of the airways
to stimuli such as inhaled histamine and methacholine (bronchial
provocation tests used to diagnose bronchial hyperreactivity).
Pathophysiology:
Primary abnormality airway narrowing:
Bronchial muscle contraction airway hyperresponsiveness to variety
of stimuli.
Mucosal swelling/inflammation mast cells and basophil degranulation
resulting in the release of inflammatory mediators.
Increased mucus production within airway lumen.
Inflammation
Increased mast cells, eosinophils, T lymphocytes and dendritic cells in
bronchial walls, mucous membranes and secretions.

o Dendritic cells initial uptake and presentation of allergens to

lymphocytes, predominantly T-helper 2 (Th2).
Allergen taken up and presented to lymphocytes (predominantly T-helper 2
(Th2) ) by dendritic cell cytokines released (IL- 3, IL-4, IL-5, IL-9 and IL-13)
migration and activation of mast cells and eosinophils.
IL-4 and IL-13 helps maintain the proallergic Th2 phenotype switches
antibody production by B lymphocytes to IgE.
IgE attach to mast cells release mediators (e.g. histamine, tryptase,
prostaglandin D2 and leukotriene C4) acts on smooth muscle and
small blood vessels immediate asthmatic reaction.
IgE binding activates eosinophils leads to mediators (e.g. eosinophilic
cationic protein predominantly toxis to airway cells) release.
Remodelling
Hypertrophy and hyperplasia of bronchial smooth muscles larger
portion of wall occupied by smooth muscle tissue.
Airway wall further thickened - deposition of repair collagen and matrix
proteins below basement membrane.
Airway epithelium is damaged, with loss of ciliated columnar cells into
the lumen.
Epithelium undergoes metaplasia + increase in mucus-secreting goblet
cells.
Precipitating factors
Major allergen house dust mite and its faeces.
Non-specific factors of wheezing
o viral infections, cold air, exercise, irritant dusts, vapours and
fumes (cigarettes, perfume, exhaust fumes), emotion and drugs
(NSAIDs, aspirin and B blockers).
Occupational asthma
o materials from workplace; veterinary medicine and animal
handling, bakery (wheat, rye) and laundry work(biological
enzymes).
Rare airborne spores of Aspergillus fumigatus.
o Clinical findings fleeting shadows on CXR and peripheral blood
eosinophilia (allergic bronchopulmonary aspergillosis).
Signs/Symptoms:
Symptoms

 dyspnoea, wheeze, chest tightness, cough (often nocturnal) and

sputum.
Tend to be intermittent, worse at ngiht and in early morning provoked by
triggers.
Ask about
Triggers, diurnal variation, disturbed sleep (severe asthma), other atopic
disease (e.g. eczema), social history (pets? Workplace?).
Signs
Tachpnoea
Audible wheeze; widespread, polyphonic expiratory wheeze
Hyperinflated chest
Hyperresonant percussion
Diminished air entry
If severe,
Inability to complete sentence, >110 bpm, RR >25/min, PEF 33-50%
predicted.
If life-threatening,
Silent chest, cyanosis, bradycardia, exhaustion, PEF <33% predicted,
confusion.
If near-fatal,
PaCO2 >6kPa, and low or falling arterial pH.
Investigations:
Diagnosis based on history and evidence of airflow obstruction (by spirometry
or PEF) when symptomatic.
Acute attacks
PEF, sputum culture, FBC, U&Es, CRP, blood cultures.
ABG
normal or slightly reduced PaO2 and low PaCO2 (hyperventilation)
If PaCO2 is raised - failing respiratory effort - transfer to ITU/HDU for
ventilation.
CXR
exclude infection or pneumothorax.
Chronic asthma
PEF monitoring
Diurnal variation > 20% on 3 days a week for 2 weeks.
Spirometry

 Obstructive defect ( FEV1/FVC, RV)

Usually 15% improvement in FEV1 after B2 agonists or steroid trial.
CXR hyperinflation.
Skin prick test to identify allergens.
Histamine and methacholine challenge; Aspergillus serology.
Complications:
Moderate exacerbation
After upper/lower airway infection or persistent allergen exposure.
Can be treated with oral corticosteroid, and use short-acting B agonist on an
as-needed basis.
Severe exacerbation
Occur in poorly controlled patients or if exposed to major trigger.
Those with history of previous near-fatal asthma attacks, multiple
hospitalisations.
Treatment Oxygen, continuous nebulised short-acting B agonist,
hydration, inhaled corticosteroid, IV magnesium.
Associated with rapid decline in lung function; decline is reduced with
inhaled corticosteroids.
Airway remodelling
Due to persistent inflammation; resembles COPD and may
progressively worsen.
Oral candidiasis secondary to inhaled corticosteroids
Most common thrush; often prevented by using spacer tube, and
rinsing, gargling, and spitting after inhaler use.
Dysphonia secondary to inhaled corticosteroids
Due to laryngeal muscle spasm causing abnormal voice.
Oesophageal candidiasis secondary to inhaled corticosteroids
HIV serology should be checked.
Associated Conditions:
COPD, GORD, Angina, pneumonia.
DDx- PE, COPD, large airway obstruction (e.g. tumour), SVC
obstruction (wheeze, dyspnoea not episodic), oneumothorax,
pulmonary oedema, bronchiectasis, obliterative bronchiolitis.
Management:
Patients should be offered influenza immunisation.
Avoid precipitating factors
CONTRAINDICATION with B-blockers of any form.
Aspirin intolerant should avoid NSAIDs.

Medication
Most drugs directly into lungs lower doses used and reduced
systemic side-effects compared to oral treatment.
Managed with stepwise approach depends on repeated PEFR
measurements.
o Starts with most appropriate to initial severity. When controlled,
treatment gradually reduced to previous step over period of 1 3
months.

B agonists
o relax smooth muscle; bronchodilation.
Antimuscarinic
o bronchodilation and may be additive to adrenoceptor stimulants.
Corticosteroids
o Inhaled used as maintenance in all but very mild patients. If not
controlled, oral.

o S/Es oral candidiasis, hoarseness and rarely cataract formation.

Anti-inflammatory agents e.g. sodium cromoglicate
o Prevents activation of inflammatory cells; may be useful in mild
asthma.
Cysteinyl leukotriene receptor antagonists (LTRAs) e.g. montelukast
o Given orally
o Useful in those who still have symptoms despite high dose
inhaled/oral corticosteroids, and in those asthma induced by
aspirin.
Steroid-sparing agents. Methotrexate, ciclosporin, anti-IgE
monoclonal antibody (omalizumab), IV immunoglobulin and etanecerpt.
Management of acute severe asthma

Prognosis:
Mild-to-moderate can improve over time, many adults become
symptom free.
Severe may experience improvement depending on degree of
obstruction in the lungs and effectiveness of treatment.
10% of severe persistent cases changes in airway wall structure,
leading to progressive and irreversible problems in lung function.