What are the 2 main categories of obstructive airways disease?
When is the onset of asthma most common?
What are the 3 main causes of asthma?
Genetic factors (predisposition)
Name some specific causes and triggers of asthma
- Pet hair
- Wood dust
- Cigarette smoke
What are the 2 broad types of asthma?
Extrinsic (atopic): The result of an inappropriate adaptive immune response to an inhaled antigen
- Associated with atopy (e.g. eczema, hay fever)
- Typical onset in childhood
- Sensitisation and effector phases
- Generally eosinophilic inflammation
- No personal or family history of asthma/atopy
- Typical onset in middle age
- Often onset following upper airway infection
- Generally neutrophilic inflammation
What histological changes occur in asthma?
Goblet cell hyperplasia
Thickening of basement membrane
Hypertrophy of smooth muscle (in response to hyper-reactivity)
Increase in inflammatory cells (macrophages, eosinophils, neutrophils, lymphocytes, mast cells)
Increase in size of mucus glands in submucosa
What is the sensitisation phase of asthma?
What is the effector phase?
- Allergen is taken up by dendritic (antigen presenting) cell
- Presented to TH2 lymphocyte
- Other immune cells (e.g. B-cells) primed to rapidly secrete IgE in presence of antigen.
- B-cells secrete IgE
- IgE binds to mast cells (major effector)
- On second major exposure to antigen this will respond.
- Mast cells secrete a number of immune substances in response to antigen:
- = ACUTE RESPONSE- BRONCHOCONSTRICTION
- Also recruit inflammatory cells:
- = LATE RESPONSE-
- Mucus secretion
- Vascular leak → oedema
- Immune cell infiltration
Which immune cell predominates in atopic asthma?
Which immune cell predominates in non-atopic asthma?
Why are anticholinergic inhalers given in the acute phase of asthma?
To inhibit the cholinergic reflex brought about by irritatation of sensory nerves in the bronchi which leads to bronchoconstriction
What occurs in the immediate/early phase of asthma?
What occurs in the late phase?
Mast cells activated by cross-linked IgE secrete substances such as histamine and tryptase which cause broncho constriction.
Mast cells activated in the early phase also activated T-lymphocytes which secrete substances such as IL-3, IL-5, TNF which recruit neutrophils and eosinophils.
- These substances, neutrophils and eosinophils cause vascular leak (oedema), increased mucus secretion and immune cell infiltration (inflammation).
What are the symptoms of chronic asthma?
- Quick onset, quick recovery of symptoms
- Acute exacerbations (asthma attacks)
- Wheeze (turbulent flow)
- SOB often worse at night
- Often associated atopy/allergens
What are the symptoms of an acute exacerbation of asthma?
- Inability to complete sentences
- Use of accessory muscles
- Reduced breath sounds if severe
How is asthma diagnosed?
Strong suspicion of asthma:
- Trial of treatments and assess response
- Good response = asthma
- Poor response =
- Spirometry before and after salbutamol (bronchodilator reversibility)
- Diurnal variation of peak flow monitoring
- Histamine challenge tests (asthmatics require small amounts to intiate bronchoconstriction)
- FeNO (fraction of exhaled)
- Blood oesinophils
- Skin prick test
What occurs in the remodelling (chronic) phase of asthma?
- Smooth muscle and epithelial cell hyperplasia
- Smooth muscle hypertrophy
- Basement membrane thickening
- Goblet cell hypertrophy, excess mucous production
What are the classifications of acute asthma?
- Increasing symptoms
- PEF >50-75% best of predicted
- No features of acute severe asthma
Acute Severe Asthma
- Any one of:
- PEF 33-50% best or predicted
- Respiratory rate >25/min
- Heart rate >110/min
- Inability to complete sentences in one breath
Life Threatening Asthma
- Any one of:
- Altered conscious level
- Silent chest
- Poor respiratory effort
- SpO2< 92%
- PEF <33% of best or predicted
- pO2<8kPa (CO2 normal)
Near fatal asthma:
- Symptoms of life threatening asthma + pCO2 raised or requiring mechanical ventilation.
Why is pCO2 often normal in patients with life threatening asthma?
Hyperventilation leads to excretion of CO2 causing hypocapnia. As bronchoconstriction gets worse and air trapping worsens, pCO2 rises and reaches a point where it is normal before it becomes raised.
How is an acute asthma exacerbation managed?
- sats 94-98%
B2 agonist bronchodilators
- Salbutamol or terbutaline (nebs/spacers) every 15-30 mins
- To address inflammation
- Prednisolone PO or IV hydrocortisone
- Minimum 5 days
- Ipratropium- add to nebulisers if poor initial response to bronchodilators
What is used to treat the immediate/early phase acute asthma?
What is used to treat the late/inflammatory phase of asthma?
What is COPD?
What are the 2 main types?
Chronic, irreversible, obstructive airway changes.
- Chronic bronchitis
What is emphysema?
Occurs in peripheral bronchioles and alveoli:
- Alveolar wall destruction
- Air space enlargement
What is chronic bronchitis?
Occurs in larger airways (bronchi, bronchioles)
- Mucus gland hypertrophy and hyperplasia = mucus hypersecretion
What are the causes of COPD?
- a1-antitrypsin deficiency (genetic predisposition)
- Pollutants (e.g. asbestos)
What are the causes of airway obstruction in COPD?
Which of these are reversible and which are irreversible?
- Accummulation of plasma exudate, inflammatory cells and mucus in the bronchi
- Smooth muscle contraction in peripheral and central airways
- Dynamic hyperinflation during exercise
- Fibrosis and narrowing of airways
- Loss of elastic recoil due to alveolar destruction
- Destruction of alveolar support that maintains patency of small airways
What are the clinical symptoms of COPD?
- Productive cough (sputum)
- Frequent infective exacerbations with purulent sputum production
- Signs of respiratory failure, cor pulmonale
How is COPD diagnosed?
Spirometry: reduced FEV1 : FVC ratio
CXR: may show hyperinflation but may also be normal.
Haemoglobin may be raised in chronic hypoxia
How is COPD managed?
- Short acting B2 agonists (salbutamol, terbutaline)
- Anticholinergics (ipratropium bromide)
- Long acting B2 agonist (salmeterol, formoterol) + inhaled corticosteroid (beclometasone, fluticasone)
Pulmonary rehabilitation (MDT management)
Vaccinations: pneumococcal, influenza