Asthma, COPD and Bronchiectasis

Question 1

Define asthma

Answer 1

• Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation
• Defined by history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation

Question 2

What are the defining characteristics of asthma

Answer 2

• Airway inflammation
  
  • Mainly eosinophilic but can also be non-eosinophilic or neutrophilic
• Intermittent airflow obstruction
• Bronchial hyper-responsiveness

Question 3

Outline the pathogenesis of asthma

Answer 3

• Asthma is a chronic inflammatory process driven by TH2 cells
• Macrophage process and present antigens to T lymphocytes - activates TH2 cells
• TH2 cells release cytokines which attract and activate inflammatory cells including mast cells and eosinophils
• TH2 cells also activate B cells which produce IgE
• Immediate response - type 1 hypersensitivity
  
  • Lasts about 20 minutes after antigen exposure
  • Allergens increase histamine and prostaglandin release from eosinophils and mast cells
    
    • Cause bronchial smooth muscle contraction leading to bronchoconstriction
• Late phase response - type IV hypersensitivity
  
  • Occurs 3-12 hours after antigen exposure
  • Inflammatory cells including eosinophils, neutrophils and lymphocytes are attracted to the target site
    
    • Release cytokines which cause airway inflammation
      - Eosinophils release leukotriene and other mediators which are toxic to epithelial cells - causes shedding of epithelial cells

Question 4

How does inflammation cause airway narrowing

Answer 4

• Goblet cell hyperplasia causes mucus hypersecretion
• Mucosal swelling (oedema) due to vascular leak
• Thickening of bronchial walls due to infiltration by inflammatory cells
• Epithelium shedding incorporated into the thick mucus
• Smooth muscle hyperplasia stimulated by growth factor release and stimulates airway remodeling
  
  • Airways easier to constrict than remain constricted
    
    • Airway remodeling long term and also due to hypertrophy of mucus glands, thickening of basement membrane

Question 5

Define specific allergen and give examples for asthma

Answer 5

• Allergens cause body to develop specific IgE antibodies that target allergen
• Pollen
• Dust
• Pets

Question 6

Define non-specific allergen and give examples for asthma

Answer 6

• Irritate airway without producing IgE antibodies
• Perfume
• Smoking
• Weather changes
  
  • Thunderstorms - make pollen particles smaller
  • Cold - release of histamine which act as bronchoconstrictors
• Exercise - increase oxygen demand and increases blood perfusion to lungs
• Emotional distress
• Drugs
• Chemicals

Question 7

What are the symptoms of asthma

Answer 7

• Wheezing
• Shortness of breath
• Chest tightness
• Cough

Question 8

What tests could be used to test for asthma

Answer 8

• Spirometry
• Challenge test
• Eosinophilic inflammation
• Skin-prick test to find out if patient is allergic
• Chest x-ray to rule out differential diagnosis

Question 9

How is spirometry used to test for asthma

Answer 9

• Low FEV1/FVC ratio (less than 0.70) with obstructive pattern on flow volume loop
• Test before and after bronchodilator - if variation seen then probably asthma
  
  • If >15% improvement after bronchodilator, then asthma
  • If < 15% improvement after bronchodilator, could be COPD or other lung disease

Question 10

Explain how the challenge test works

Answer 10

• Histamine challenge airway hyper-responsiveness
• Give doses of histamine and measure -FEV1 until it falls by 20%
• If FEV1 does not fall significantly, then not asthma

Question 11

Describe how eosiniphillic inflammation can be measured

Answer 11

• Peripheral blood eosinophil count (FBC)
• Induced sputum (eosinophils, neutrophils)
• FeNO (exhaled nitric oxide) - marker for inflammation

Question 12

Outline the treatment of asthma

Answer 12

• ß2 agonists used to relieve symptoms of asthma - cause bronchodilation
  
  • Short acting bronchodilator - salbutamol
  • Long acting bronchodilator - formoterol
• Corticosteroids used to treat inflammation of airways and prevent attacks
  
  • Inhaled corticosteroids - budesonide
    
    • Preferred as directly enter the target site
    • Oral corticosteroids - prednisolone

Question 13

Describe the signs and symptoms of acute severe asthma

Answer 13

• Worsening symptoms - cough, breathlessness, wheeze, chest tightness, chest pain
  
  • High respiratory rate ≥ 25/min
  • High heart rate ≥ 110/min
  • Inability to complete sentences on one breath
  • Peak expiratory flow - 33-50% best
• Increase in pCO2 - body unable to cope with hyperventilation (life threatening asthma)
  
  • Possible transition from type 1 to type 2 respiratory failure

Question 14

Describe the treatment of severe acute asthma

Answer 14

• High flow oxygen - aim to keep sats at 94-98%
• Nebulised salbutamol - continuous if necessary
• Oral prednisolone (corticosteroid)
• If still not responding, give nebulised ipratropium bromide and IV magnesium as bronchodilators

Question 15

Describe the causes of COPD

Answer 15

• Smoking (90%)
  
  • Approximately only 15% who smoke get COPD
• Alpha-1-antitrypsin deficiency - deficiency leads to imbalance of proteinases and antiproteinases
  
  • Leads to destruction of alveolar walls and emphysema
• Occupational exposure - coal dust
• Pollution

Question 16

Define emphysema

Answer 16

• Swelling of alveoli loses its elasticity and causes them to permanently enlarge
• Impairment of gas exchange

Question 17

Describe the pathogenesis of emphysema

Answer 17

• Inflammation of the alveoli walls triggered by irritants such as cigarette smoke
  
  • Immune cells attracted which causes release of proteases and other inflammatory mediators
  • Proteases breakdown structural proteins such as collagen and elastin, which give lungs its elastic nature
• When exhaling, low pressure within the alveoli/tubule and high pressure in the chest pull the walls inwards
  
  • Loss of elastin means walls are pulled inwards and collapse in exhalation
• Makes lungs more compliant, as walls are able to expand more and contain more air - hyper-inflation
  
  • Leads to large airspaces in acinus called bullae
• Alpha-1 antitrypsin - protease inhibitor to protect against collapse of airsacks

Question 18

Describe the pathogenesis of chronic bronchitis

Answer 18

• Caused by inflammation in the large airways leading to proliferation of mucus producing cells
  
  • Goblet cells replace ciliated respiratory epithelium
• Loss of ciliary function
• Leads to chronic productive cough and frequent respiratory infections
• Results in airflow obstruction due to remodelling and narrowing of the airways

Question 19

Describe hoe COPD can lead to peripheral oedema

Answer 19

• Progressive hypoxia causes pulmonary vasoconstriction and vascular muscle thickening due to increased pulmonary resistance
  
  • Leads to pulmonary hypertension and right heart failure (cor pulmonale)

Question 20

Describe the symptoms of COPD

Answer 20

• Cough and sputum production
• Progressive breathlessness
• Breathless on exertion

Question 21

Describe the signs of COPD

Answer 21

• Purse lip - increases the pressure within airways and keeps airways from collapsing
  
  • Typical of emphysema
• Tachypnoea - increased respiratory rate to compensate for hypoxia and hypoventilation
• Use of accessory muscles of respiration - bending down to aid breathing
• Barrel chest - due to hyperinflation and air trapping secondary to incomplete expiration (emphysema)
• Hyper-resonance on percussion - air trapping
• Reduced intensity breath sounds - caused by barrel chest, hyperinflation and air trapping
• Reduced air entry - loss of lung elasticity and lung tissue breakdown
• Wheezing and crackling

Question 22

Outline the investigation of COPD patients

Answer 22

• Spirometry - obstructive pattern with FEV1/FVC ratio < 0.70
  
  • Both FEV1 and FVC decrease but FEV1 decreases more
  • Limited reversibility following treatment with bronchodilators
  • Normally sufficient in diagnosing COPD alongside good history
• Decreased diffusing capacity of the lung for carbon monoxide shows emphysema
• Chest x-ray - hyper-inflated lungs may result in flattened diaphragm, hyperlucent lungs, increased antero-posterior diameter of the chest
  
  • Rule out other pathologies such as lung carcinoma
• Pulse oximetry and arterial blood gas
  
  • Carried out in acutely unwell patients to assess for hypoxia and hypercapnia
• Alpha-1 antitrypsin level
  - Checked if suspicion of positive family history and atypical COPD (young patients who do not smoke)

Question 23

Outline the treatment of COPD

Answer 23

• Smoking cessation
• Patient education
• Monitor patient weight, nutrition, physical activity
• Bronchodilators and inhaled corticosteroids
• Pulmonary rehabilitation - many patients avoid exercise because of breathlessness
  
  • Leads to muscle weakness, depression and social isolation
  • Pulmonary rehabilitation aims to break this cycle and suggest exercise and nutritional advice
• Long term oxygen treatment - extended periods of hypoxia cause pulmonary hypertension
• Surgical interventions - removal of large bullae, lung volume reduction
• Check inhaler technique
• Non invasive ventilation - for acute exacerbation of COPD with type II respiratory failure (when patient fails to hyperventilate)

Question 24

Describe what bronchiectasis is

Answer 24

• Chronic dilation of one or more bronchi

- Bronchi exhibit poor mucus clearance and there is predisposition to recurrent or chronic bacterial infection

Question 25

Describe the investigation of bronchiectasis

Answer 25

- High resolution CT scan - bronchial dilation bigger than the adjacent blood vessel - Bronchial wall thickening - Signet ring sign

Question 26

List the symptoms of bronchiectasis

Answer 26

- Chronic cough - Daily sputum production - Breathlessness on exertion - Intermittent hemoptysis - Nasal symptoms - Chest pain - Fatigue

Question 27

Describe potential causes of bronchiectasis

Answer 27

- Post-infection - whooping cough, TB - Immune deficiency - low immunoglobulin levels - Mucociliary clearance defects - genetic causes - Cystic fibrosis

Question 28

Describe the management of bronchiectasis

Answer 28

- Treat underlying cause - Physio/airways clearance - mucus clearance - Sputum sampling - antibodies according to sputum cultures

Question 29

Describe the pathophysiology of cystic fibrosis

Answer 29

- Autosomal recessive disorder - Chromosome 7 defect leads to cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation - CFTR pumps secretes chloride ions which drives water out through osmosis - Mutation leads to ineffective cell surface chloride transport - Leads to thick, dehydrated body fluids in organs which have CFTR as water is not drawn out - Reduced mucus movement through cilia means that bacteria can more likely infect airways

Question 30

Describe how to diagnosis cystic fibrosis

Answer 30

- History of CF in sibling - Positive newborn screening test results - Increased sweat chloride concentration - sweat test - Chloride cannot be reabsorbed - Genotyping - identification of two CF mutations

Question 31

Describe the presentation of cystic fibrosis

Answer 31

- Meconium ileus - thickened meconium causing bowel obstruction in newborn - Intestinal malabsorption - pancreatic enzyme insufficiency - Thick secretions block pancreatic ducts - Chest infections

Question 32

Describe the management of cystic fibrosis

Answer 32

- Maintain lung health and nutritional state - No smoking - Pancreatic enzyme supplements - Bronchodilators

Question 33

Distinguish between COPD and asthma

Answer 33

- COPD has persistent, productive cough, Asthma has intermittent and usually non-productive cough - COPD typically due to smoking - COPD presents with breathlessness at night, asthma has coughing and wheezing at night - Asthma more common in family history - COPD mainly neutrophils and macrophages, asthma mainly eosinophils and mast cells - COPD irreversible in spirometry, asthma reversible