Respiratory Flashcards
Define chronic obstructive pulmonary disease (COPD)
Chronic obstructive pulmonary disease (COPD) is a progressive, irreversible obstructive lung disease characterised by airflow limitation that is not fully reversible. It encompasses both emphysema and chronic bronchitis.
What is emphysema?
Emphysema involves loss of alveolar integrity due to an imbalance between proteases and protease inhibitors (e.g. alpha-1 antitrypsin).
Elastase breaks down elastin > increased loss of elastin. Triggered by chronic inflammation, such as smoking.
What is chronic bronchitis?
Bronchitis involves excessive mucus secretion secondary to ciliary dysfunction and increased goblet number and size → lung parenchymal destruction → impaired gas exchange. Chronic bronchitis is long-term bronchitis.
What are the risk factors for developing COPD?
- Age: usually diagnosed after the age of 45
- Tobacco smoking: greatest risk factor
- Air pollution
- Occupational exposure: such as dust, coal, cotton, cement and grain
- Alpha-1 antitrypsin deficiency: younger patients present with features of COPD
What signs and symptoms might patients with COPD present with?
The disease can range from mild to severe.
Mild symptoms - occasional bronchodilator
Severe symptoms - frequent exacerbation need hospital admission.
1) Symptoms
- Dyspnoea: particularly on exertion
- Cough: often productive
- Wheeze
2) Signs
- Tachypnoea
- Barrel chest (bulging of the chest)
- Hyperresonance on percussion
- Tar staining of fingers with peripheral cyanosis
3) Evidence of an exacerbation:
- Significant dyspnoea, wheeze and cough
- Coarse crepitations (lung crackles)
- Pyrexia
- Evidence of cor pulmonale (right-sided heart failure due to severe COPD): e.g. peripheral oedema
What investigations/tests are used to diagnose COPD?
Primary investigations:
1) Spirometry: FEV1/FVC <0.70 + bronchodilator reversibility (BDR): lack of reversibility post-bronchodilator is indicative of COPD (not required for diagnosis)
2) Chest X-ray: flattened diaphragm, hyperinflation and bullae. Carried out to detect lung cancer.
3) FBC: COPD causes chronic hypoxia, which may result in secondary polycythaemia (high levels of RBC).
4) FBC is also required to determine is eosinophilia (abnormally high eosinophil levels) is present
5) Calculate body mass index (BMI)
What is FEV1/FVC?
FEV1: forced expiratory volume; the volume of air exhaled in the first second of forced exhalation
FVC: forced vital capacity; the volume exhaled after maximal expiration following full inspiration
Normal FEV1/FVC = above 0.75-85
What does an FEV1/FVC ratio of <0.7 indicate?
Obstructive disease e.g. COPD or asthma
What are the general management principles for COPD?
Smoking cessation
Pulmonary rehabilitation: for patients who are self-perceived as functionally disabled by COPD (e.g. MRC grade ≥3)
Vaccinations: one-off pneumococcal and annual influenza
Initial therapy:
All patients will be started on a short-acting bronchodilator PRN (pro ra nata - as needed) (e.g. salbutamol) and may have additional long-acting agents
What is the GOLD classification for COPD?
Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups patients according to severity to guide treatment.
Stage 1: Mild
Post-bronchodilator FEV1/FVC: <0.70
FEV1 (% of predicted): ≥80%
Stage 2: Moderate
Post-bronchodilator FEV1/FVC: : <0.70
FEV1 (% of predicted): 50-79%
Stage 3: Severe
Post-bronchodilator FEV1/FVC: : <0.70
FEV1 (% of predicted): 30-49%
Stage 4: Very severe
Post-bronchodilator FEV1/FVC: :<0.70
FEV1 (% of predicted): <30%
What are the medications used in managing COPD?
1) SABA: short-acting beta-adrenoceptor agonist (e.g. salbutamol) - leads to bronchodilation
2) SAMA: short-acting muscarinic antagonist (ipratropium) - inhibits smooth muscle contractions
3) LABA: long-acting beta-adrenoceptor
agonist (e.g. salmeterol) - leads to bronchodilation
4) LAMA: long-acting muscarinic antagonist (e.g. tiotropium) - inhibits smooth muscle contraction
5) ICS: inhaled corticosteroid (e.g. beclomethasone)
What are the medications used in managing asthma?
1) SABA (short-acting beta-agonist); e.g. salbutamol
2) ICS (inhaled corticosteroid); e.g. beclomethasone.
3) LTRA (leukotriene receptor antagonist); e.g. montelukast (reduces inflammation, not a steroid)
4) LABA (long-acting beta-agonist); e.g. salmeterol
5) MART (maintenance and reliever therapy); combined fast-acting LABA and ICS for symptomatic relief and maintenance in a single inhaler.
DDx for COPD
- Asthma
- Congestive heart failure
- Bronchiectasis
Salmeterol
1) Use
2) MOA
3) Side effects
1) Reversible airways obstruction in COPD, asthma for patients needing long-term bronchodilation
2) Activation of β adrenergic receptors leading to relaxation of smooth muscle in the lung, and dilation and opening of the airways
3) Arrhythmias; headache; palpitations; tremor
What is the management plan for COPD according to the GOLD classifcation?
GOLD A
Exacerbations: ≤1 per year not requiring admission
Symptoms between exacerbations: mild
Inhaler: any bronchodilator (short or long-acting)
GOLD B
Exacerbations: ≤1 per year not requiring admission
Symptoms between exacerbations: severe
Inhaler: LABA or LAMA
GOLD C
Exacerbations: ≥ 2 per year OR 1 requiring admission
Symptoms between exacerbations: mild
Inhaler: LAMA
GOLD D
Exacerbations: ≥ 2 per year OR 1 requiring admission
Symptoms between exacerbations: severe
Inhalers:
LAMA or
LAMA + LABA or
LABA + ICS
What are the NICE guidelines for managing COPD?
In clinical practice, GOLD classification used more often to manage COPD.
NICE guidelines are based on whether the patients have asthma symptoms.
Initial managment: COPD diagnosis = SAMA or SABA
Scenario 1: if symptoms persist AND asthma symptoms/previously diagnosed asthma > commence LABA & ICS
Scenario 2: if symptoms persist but no asthma > commence LABA & LAMA
If above therapies ineffective > commence LAMA, LABA & ICS
Define asthma
Asthma is a chronic inflammatory airway disease characterised by intermittent airway obstruction and hyper-reactivity.
What is the aetiology of asthma in adults?
A complex interaction between genetic and environmental factors.
Asthma usually starts with a genetic susceptibility which predisposes patients to airway hyper-responsiveness. It is then triggered by environmental factors such as viral infection, allergens (the main cause in children), cold and exercise
What is the aetiology of asthma in children?
In children, the cause is commonly atopy (genetic tendency to develop allergic diseases) and exposure to allergens (pollen, dust mites, animal fur, pollution).
Associated atopic conditions are eczema, hayfever.
What is the pathophysiology of asthma in adults?
Much like asthma in children, the inflammatory response in asthma is driven by Th2 cells → secretion of inflammatory mediators (IL-3, IL-5, IL-10, IL-13)
This results in eosinophil activation, IgE production and mast cell degranulation.
Ultimately this causes smooth muscle contraction > bronchiole constriction and increased mucus production > initially reversible airflow obstruction > irreversible over time due to fibrosis and tissue damage > permanent reduction in airway diameter
What is the pathophysiology of asthma (osmosis)?
Chronic asthma (PTS SAQ) - The primary abnormality in asthma is narrowing of the airway, which is due to smooth muscle contraction, thickening of the airway wall by cellular infiltration and inflammation, and the presence of secretions within the airway lumen
A trigger (e.g. cigarette smoke) detected by dendritic cells > present antigen to T-helper 2 cells
TH2 cells produce IL-4 and IL-5
IL-4 stimulates production of IgE which cause mast cell degranulation e.g. histamine
IL-5 stimulate eosinophils which release inflammatory mediators and leukotrienes
Minutes after exposure > bronchiole smooth muscles contract + increased mucus > airway narrowing and difficulties breathing
Also increase in vascular permeability >
recruitment of additional immune cells from the blood.
Hours after exposure, eosinophils release chemical mediators that damage the lung endothelium.
Initially, the damage is reversible but over time become irreversible.
Oedema, scarring, and fibrosis > permanent reduction in airway diameter
What are the risk factors for asthma in adults?
History of atopy: such as eczema and allergic rhinitis (IgE-mediated atopic conditions)
Family history
Allergens: such as tobacco smoke, pets, outdoor air pollution
Viral upper respiratory tract infection
Other triggers: cold weather and exercise
Occupational exposure (10-15%): e.g. spray paint, flour (bakers), people involved in plastic, foam and glue manufacturing. Requires a specialist referral
What are the risk factors for developing asthma in children?
1) Personal or family history of atopy: e.g. eczema and allergic rhinitis
2) Passive smoking
3) Antenatal factors: maternal smoking, RSV infection during pregnancy
4) Low birthweight
5) Bottle-fed (rather than breastfed)
6) Significant allergen exposure: e.g. dust mites, pets, tobacco smoke or air pollution
7) Childhood infection with a respiratory syncytial virus (RSV) MIGHT increase asthma risk
8) ‘Hygiene hypothesis’: reduced exposure to the developed world is theorised to lead to reduced ability of the child’s body to differentiate between harmful and harmless substances > increased asthma risk
Reduced exposure causes a Th2-predominant response.
What signs and symptoms might an adult patient with asthma present with?
Symptoms
1) Episodic shortness of breath with diurnal variation, i.e. worse at night and early morning
2) Dry cough
3) Wheeze and ‘chest tightness.’
4) History of exposure to a trigger
Signs:
1) Diural peak expiratory flow rate (PERF - the volume of air forcefully expelled from the lungs in one quick exhalation)
2) Dyspnoea and expiratory wheeze
3) Samter’s triad: sinus inflammation (nasal polyps), aspirin sensitivity and asthma
What signs and symptoms might a paediatric patient with asthma present with?
Symptoms:
1) Episodic shortness of breath
2) Dry cough
3) Wheeze and ‘chest tightness’
4) Features of atopic disease: e.g. eczema
Signs:
1) Diurnal peak expiratory flow rate (PEFR) variation
2) Dyspnoea and wheeze
What investigations/tests are used to diagnose asthma in adults?
Primary investigations:
- Spirometry: FEV1/FVC <70% suggests obstruction. If obstruction is found, BDR should be carried out
- Bronchodilator reversibility (BDR): improvement of FEV1 by ≥12% and increase ≥200ml in volume post-bronchodilator (bronchodilator irreversible would indicate COPD instead)
- Peak expiratory flow rate (PEFR) - measured multiple times a day over 2-4 weeks.
- PEFR - Morning lower, evening higher. Diurnal variation
- Variability of >20% throughout the day is diagnostic - compared with patient’s PB or normal values for age, height and gender
What investigations/tests are used to diagnose asthma in children?
Children aged < 5 years:
- Diagnose and treat based on clinical judgement, with regular reviews until ≥ 5
Children aged 5-16 years:
- Spirometry is 1st investigation; FEV1/FVC <70% is a positive result (obstructive)
- Bronchodilator reversibility (BDR): consider if obstructive spirometry is present; an improvement of FEV1 by ≥12% = positive
- PEFR often performed in adult but inconclusive in children
What is the management plan for asthma in adults?
Occupational exposure = they should be referred to a specialist.
Occupational asthma = symptoms and reduced PEFR during the working week and improvement when not at work.
Step 1: Newly-diagnosed asthma: SABA (PRN)
Step 2: If symptoms not controlled through SABA: SABA + low-dose ICS
Step 3: SABA + low dose ICS + LTRA
Step 4: SABA + low dose ICS + LABA +/- LTRA dependent on response
What is the management plan for asthma in children?
Children < 5 years old: clinical judgement must also be used
Step 1: newly-diagnosed asthma = SABA
Step 2: not controlled on the previous step
= SABA + trial paediatric moderate dose ICS for 8 weeks + review after
Step 3: SABA + paediatric low dose ICS + LTRA
Step 4: Stop LTRA + seek expert opinion
Children 5 - 16= similar management as adults:
Step 1: SABA
Step 2: SABA + ICS
Step 3: SABA + ICS + LTRA
Step 4: SABA + ICS + LABA (STOP LTRA)
DDx for asthma
Adults
- Cystic fibrosis
- COPD
- Chronic rhinosinusitis
Children
- Bronchiolitis
- Episodic (viral) wheeze triggered only by viral infection
- Inhaled foreign body
What is asthmatic exacerbation?
When triggers such as pollen, pollution, infection and exercise cause bronchoconstriction and inflammation in patients with asthma.
Patients with asthma have hyperreactive airways, which makes them more suspectable to the above triggers.
The inflammatory response is usually driven by Th2 cells, particularly if the trigger is an allergen.
Type 1 hypersensitivity reaction
What is the management plan for asthmatic exacerbations in adults?
1) Immediate management:
- Oxygen: SpO2 94-98%
- Nebulised bronchodilators: salbutamol 5mg is first-line
- Corticosteroids: prednisolone 40mg OD or 100mg hydrocortisone IV. Patients should continue on their inhaled corticosteroids.
- ICU and IV bronchodilator if above ineffective
Discharge:
Patients can be discharged once their PEFR > 75%
Given a course of oral steroids, inhaled steroids, and inhaled bronchodilator
GP appointment within 48 hours of discharge and an asthma plan
What is the management plan for asthmatic exacerbations in children?
1) General management for all severities:
Oxygen: in life-threatening asthma or if SpO2 <94%
Bronchodilators: Inhaled salbutamol (1st line) +/- ipratropium bromide:
Corticosteroids:
Oral prednisolone is given if the child is alert and able to swallow; otherwise, offer IV hydrocortisone
Usually 3-day course, but spends on the severity
2) Severe or life-threatening exacerbation:
Intravenous bronchodilation: magnesium sulphate may be needed if the child does not respond to the above
Other IV bronchodilators: second-line options include IV salbutamol and aminophylline
Ventilation: non-invasive ventilation or intubation if no response to above
Other considerations:
3) Antibiotics: may be used where the underlying trigger is a suspected bacterial infection
Define tuberculosis (TB)
Primary TB: a granulomatous disease caused by Mycobacterium tuberculosis.
Secondary TB: reactivation after becoming immunocompromised
What is the pathophysiology of primary TB?
Mycobacterium tuberculosis can thrive in the body because macrophages struggle to clear M. tuberculosis due to its waxy mycolic acid capsule, which confers protection. Same reason it can only be stained with Ziehl-Neelsen stain and not gram-stain as it is acid-fast.
1) Initial exposure
2) Formation of caseating granuloma (a collection of epithelioid histiocytes) in the lower lobe called Ghon focus. Ghon complex = granuloma + associated hilar lymph lobe)
3) The granuloma has caseous necrosis in the centre due to dead tissue > containing infection and will undergo fibrosis > dormant
If the patient is immunocompromised - Ghon focus reactivated > more areas of caseating granuloma > cavities = spread
4) This inflammatory process is a type 4 hypersensitivity reaction.
Primary infection is often asymptomatic.
What is a latent TB infection
This occurs after primary infection, patients remain asymptotic with a negative sputum test but a positive Mantoux test.
Might proceed to secondary TB infection if the patient is immunocompromised.
What is secondary TB?
When latent TB reactivates in immunocompromised patients because the immune system cannot contain the infection.
It can then spread systemically, resulting in miliary TB.
What are the risk factors for developing TB?
1.7 billion people worldwide have latent TB [
1) Contact with a person with active TB
2) Endemic regions: South Asian or sub-Saharan Africa
3) Homelessness
4) Alcohol or drug abuse
5) Immunocompromised: e.g. secondary to HIV, steroid use or malnutrition
What signs and symptoms might a patient with active TB disease present with?
Latent TB is asymptomatic and not infectious, unlike active disease:
Symptoms
1) Haemoptysis
2) Dyspnoea
3) Systemic symptoms:
- Fever
- Weight loss
- Night sweats
- Lymphadenopathy
Signs:
1) Auscultation: often normal; crackles may be present
2) Clubbing: if long-standing
What investigations/tests are used to diagnose TB?
1) Latent disease
- Mantoux screening: for high risk patients
2) Active disease
- 1st line is CXR: Ghon complex is visible in latent disease, whilst upper zone cavitating lesions are seen in active disease
- Microbiology: 3 deep cough sputum samples, analyse with Ziehl-Neelsen stain and Mycobacterium culture
- Nucleic-Acid Amplification Test (NAAT): rapid diagnostic test conducted on sputum or urine if HIV or at risk of MRSA
- HIV and hepatitis status: assess for co-infection
DDx for TB
Pulmonary
- COVID-19
- Community-acquired pneumonia
- Lung cancer
Extrapulmonary
- Lymphoma
- Sarcoidosis
What is the Mantoux test (tuberculin skin test (TST))?
Detects previous immune response to TB. This indicates possible previous vaccination, latent or active TB.
Intradermal injection of tuberculin and the site is inspected 48-72 hours later.
If positive, a type IV hypersensitivity reaction occurs, measured as a diameter of induration (lump) that occurs across the forearm
What is the management plan of latent and active TB?
1) Management of Latent TB:
Patients at risk of reactivation of latent TB can be treated with either:
- Isoniazid and rifampicin for 3 months
- Isoniazid for 6 months
2) Management of active pulmonary TB - coordinated MDT and TB specialist
RIPE - the combination of 4 drugs
R – Rifampicin for 6 months
I – Isoniazid for 6 months
P – Pyrazinamide for 2 months
E – Ethambutol for 2 months
Negative follow-up sputum test = successful treatment
3) Other Management Considerations:
- Test for other infectious diseases (HIV, hepatitis B and hepatitis C).
- Test contacts for TB.
- Notify Public Health of all suspected cases.
- Patients with active TB isolated until established on treatment (~2 weeks)
- Negative pressure rooms used in hospitals, these rooms have ventilation that removes air to prevent spread to the wards.
What are some extrapulmonary manifestations of TB?
1) Central nervous system: TB meningitis; the most serious complication
2) Vertebral bodies: Pott’s disease (MSK TB)
3) Adrenals: Addison’s disease
4) Gastrointestinal tract
5) Renal system
6) Genitourinary: e.g. tuberculous epididymitis
What is the treatment for TB meningitis?
Active tuberculosis of the central nervous system:
A longer continuation phase of antibiotics (rifampicin and isoniazid) for ≥ 10 months
Dexamethasone or prednisolone is also required.
Define cystic fibrosis
Cystic fibrosis (CF) is an inherited, autosomal recessive, multi-system disease due to mutations in the CF transmembrane conductance regulator (CFTR) gene on chromosome 7, CFTR is a chloride channel found in cells lining the lungs, intestines, pancreatic ducts, sweat glands, and reproductive organs.
What is the aetiology of cystic fibrosis?
Δ-F508 is the most common mutation, where the codon for phenylalanine (F) in the CFTR gene is deleted, resulting in proteolytic degradation.
CFTR is a chloride channel, and mutation causes dysfunctional Na+ and Cl- movement across membranes, resulting in the numerous systemic manifestations of the disease.
What are the risk factors for developing cystic fibrosis?
- Family history of CF
- Known carrier status of both parents
- Ethnicity - white
What is the pathophysiology of cystic fibrosis?
CFTR is an epithelial cAMP-regulated chloride channel and mutation causes dysfunctional Na+ and Cl- movement across membranes.
Resulting systemic manifestation:
1) Respiratory system
- Dry airways and impaired mucociliary clearance: results in cough, dyspnoea and recurrent pneumonia
- Increased risk of bacterial colonisation e.g. Staphylococcus aureus & Pseudomonas aeruginosa (worsens prognosis)
- Inflammation: chronic inflammatory response leads to bronchiectasis
2) Gastrointestinal
- Thickened secretions within small and large bowel: presents with failure to pass meconium (newborn first poop) and can cause bowel obstruction
3) Pancreatic insufficiency
- Defects in ion transport impede the secretion of crucial enzymes: resulting in malabsorption
3) Liver cirrhosis
Thickened biliary secretions: may block the bile ducts resulting in liver fibrosis, cirrhosis and portal hypertension
Right heart failure
Occurs due to pulmonary hypertension, resulting in cor pulmonale
What are the key infective microorganisms that colonise the respiratory system in cystic fibrosis?
Staph aureus and pseudomonas aeruginosa
Patients with cystic fibrosis take long-term prophylactic flucloxacillin to prevent staph aureus infection.
Pseudomonas aeruginosa should be remembered as a particularly troublesome coloniser that is hard to treat and worsens the prognosis of patients with cystic fibrosis.
What signs and symptoms might a patient with cystic fibrosis present with?
- Chronic cough
- Thick sputum production
- Recurrent respiratory tract infections
- Loose, greasy stools (steatorrhoea) due to a lack of fat digesting lipase enzymes
- Abdominal pain and bloating
- Parents may report the child tastes salty due to the concentrated salt in the sweat
- Poor weight and height gain (failure to thrive)
Signs
- Low weight or height on growth charts
- Nasal polyps
- Finger clubbing
- Crackles and wheezes on auscultation
- Abdominal distension
What signs and symptoms might a neonatal with cystic fibrosis present with?
- Prolonged jaundice
- Meconium ileus (bowel obstruction due to thickened meconium)
What signs and symptoms might an adult patient with cystic fibrosis present with?
- Recurrent chest infections
- Atypical asthma
- Diabetes mellitus (pancreatic insufficiency
- Male infertility: absence of vas deferens
- Female subfertility
What is the gold standard investigation for diagnosing cystic fibrosis?
Sweat test
A skin patch is chosen for the test, typically on the arm or leg.
Pilocarpine is applied to the skin and electrodes pass electrical currents, causing the skin to sweat. The sweat is absorbed with a special gauze or filter paper > lab tests for the chloride concentration.
cystic fibrosis > 60mmol/l chloride concentration (normal <40mmol/l)
What other primary investigations are used to diagnose cystic fibrosis?
Guthrie test: heel-prick test for serum immunoreactive trypsinogen (IRT) at 5-days old
Genetic testing: Δ-F508 is the most common mutation (80% of cases in the UK).
What is the management plan for cystic fibrosis?
1) 1st line: Chest physiotherapy several times a day
2) Plus: Bronchodilators such as salbutamol inhalers for bronchoconstriction and nebulised hypertonic saline (thins mucus)
3) Plus: inhaled mucolytic: nebulised DNase (dornase alfa) - enzyme that can break down DNA material in respiratory secretions, making it less thick and easier to clear
Consider the following
- Exercise improves respiratory function and reserve, and helps clear sputum
- Prophylactic flucloxacillin
- Treat chest infections
- Vaccinations including pneumococcal, influenza and varicella
GI disease
- High-calorie, high-fat diet
- CREON tablets to digest fats in patients with pancreatic insufficiency (these replace the missing lipase enzymes)
What are some other treatment options for cystic fibrosis?
1) Lung transplantation in end-stage respiratory failure
2) Liver transplant in liver failure
3) Fertility treatment involving testicular sperm extraction for infertile males
4) Genetic counselling
Define pneumonia
Pneumonia is an infection of the lung tissue. It causes inflammation of the lung tissue and sputum fills the airways and alveoli. Pneumonia can be seen as consolidation on a chest x-ray.
What is community-acquired pneumonia?
Pneumonia acquired outside of healthcare facilities (most common).
What is hospital-acquired pneumonia?
Occurs ≥ 48 hours after hospital admission.
What is the aetiology of community-acquired pneumonia (CAP)?
1) Streptococcus pneumoniae (pneumococcus):
- The most common cause of pneumonia (80%)
- Associated with rapid-onset and a high fever
- Pneumococcal vaccination is available.
2) Haemophilus influenza - associated with COPD
3) Staphylococcus aureus
- Commonly causes secondary bacterial infection after a viral URTI or the flu and can result in an abscess and empyema (pockets of pus).
What is atypical CAP?
Atypical CAP is caused by atypical organisms which are hard to gram stain and culture. Often presents with minimal respiratory symptoms and causes interstitial inflammation, meaning CXR is often normal.
What is the aetiology of atypical CAP?
1) Mycoplasma pneumoniae - commonly seen in young adults and is associated with Rauyand’s, autoimmune haemolytic anaemia and erythema multiforme
2) Legionella pneumophila - history of exposure to water source e.g. air conditioning. Associated with hyponatraemia, lymphopenia and deranged LFTs
3) Chlamydia psittaci - exposure to birds
What is the aetiology of hospital-acquired pneumonia (HAP)?
- Pseudomonas aeruginosa
- E.coli
- Staphylococcus aureus
May require broad-spectrum antibiotics
What are the risk factors for developing pneumonia?
1) Extremes of age: young children and the elderly are particularly at risk
2) Preceding viral infection
3) Immunosuppressed: e.g. due to steroid use
4) Intravenous drug abuse: Staphylococcus aureus
5) Respiratory conditions: asthma, COPD, malignancy, cystic fibrosis
What signs and symptoms might a patient with pneumonia present with?
Symptoms
- Productive cough
- Red currant jelly sputum is classically seen in Klebsiella pneumoniae
- Pleuritic chest pain
- Dyspnoea
Signs:
- Reduced breath sounds, and coarse crepitations
- Hypoxia
- Tachycardia
- Pyrexia
What investigations/tests are used to diagnose pneumonia?
- Definitive diagnostic test: CXR - classic finding is localised/widespread consolidation caused by inflammatory exudate within alveoli and bronchioles.
- FBC- ↑ WCC, ↑ urea, ↑ CRP (sign of inflammation)
- U + E - deranged in severe disease
- Sputum culture - causative organism
- ABG: perform if hypoxic to assess for respiratory failure
What is the CURB-65 score?
CURB -65 score is used to assess the severity of pneumonia, 1 point each for:
- Confusion (Abbreviated Mental Test Score ≤ 8, or disorientation in person, place or time)
- Urea > 7mmol/l
- Respiratory rate ≥ 30/min
- BP < 90mmHg systolic and/or<60mmHg diastolic
- Age ≥ 65
0-1 – outpatient treatment (home)
2 – consider hospital admission or close outpatient management
>3 – consider intensive care
What are the general principles for managing pneumonia?
- Maintain O2 sats at 94-98% (COPD 88-92%)
- Antibiotics
- Analgesia
- Fluids
What is the management plan for community-acquired pneumonia?
1) Low severity (CURB ≤ 1): oral amoxicillin OR doxycycline/clarithromycin if penicillin-allergic or atypical microorganism - 5-day course
- 1st line during COVID-19 = doxycycline
2) Moderate severity (CURB 2): amoxicillin; add clarithromycin if an atypical pathogen is suspected; usually a 5-day course
3) High severity (CURB ≥ 3): IV co-amoxiclav and clarithromycin
What is the management plan for hospital-acquired pneumonia?
1) Low severity: oral co-amoxiclav
2) High severity: a broad-spectrum antibiotic, such as IV tazocin or ceftriaxone
3) Suspected or confirmed MRSA: add vancomycin
Define bronchiectasis
Bronchiectasis is a chronic, debilitating lung disease characterised by the permanent dilation of the bronchi.
What is the aetiology of bronchiectasis?
Bronchiectasis is typically caused by chronic bronchial inflammation caused by previous infection(s) or systemic inflammatory conditions (e.g. cystic fibrosis, RA or IBD) or lung cancer.
What is the pathophysiology of bronchiectasis?
Chronic inflammation in bronchiectasis activates proteases, which break down elastin and other structures, leading to the dilatation of bronchi.
Dilated bronchi increase the risk of persistent microbial colonisation, which perpetuates inflammation, leading to increased mucus secretion and mucus trapping due to the dilated bronchi.
Due to the dilation and obstruction of the airways, an obstructive pattern is seen on spirometry.
What is the aetiology of bronchiectasis?
Bronchiectasis is typically caused by chronic bronchial inflammation caused by previous infection(s) or systemic inflammatory conditions (e.g. cystic fibrosis, RA or IBD) or lung cancer.
What bacteria most commonly colonise the respiratory tract in patients with bronchiectasis?
Haemophilus influenzae (most commonly), Pseudomonas aeruginosa, Klebsiella and Streptococcus pneumoniae.
What are the risk factors for developing bronchiectasis?
1) Age: Approximately 1% of people over the age of 70 have bronchiectasis
2) Smoking
3) Female sex
4) Genetic factors: e.g. cystic fibrosis
What investigations/tests are used to diagnose bronchiectasis?
1) Chest X-ray: dilated airways with thickened walls appear as ‘tram-tracks’ (Kerley b lines)
2) High-resolution CT chest: gold standard test as shows bronchial dilation and bronchial wall thickening
3) Sputum cultures: identify colonising pathogens (most commonly seen is Haemophilus influenza)
4) FBC: assess for superimposed infection.
5) Lung function tests: demonstrates an obstructive pattern (FEV1/FVC ratio < 70%)
What is the management plan for bronchiectasis?
First-line:
1) Treating the underlying cause
2) Chest physiotherapy: breathing techniques and airway clearance exercises and pulmonary rehabilitation
3) Annual influenza vaccination
4) Antibiotics: for acute exacerbations of bronchiectasis
DDx for bronchiectasis
- COPD
- Asthma
- Pneumonia
Define type 1 respiratory failure.
Type 1 respiratory failure is defined by a low PaO2 (hypoxia) and low/normal PaCO2 (hypocapnia/normal).
Lungs fail to fill properly.
What are the causes of type 1 respiratory failure?
- Infection (e.g. pneumonia, bronchiectasis)
- Airway diseases (COPD, asthma)
- Vasculature (pulmonary embolism, fat embolism)
- Sarcoidosis (rare condition that causes small patches of red and swollen tissue, called granulomas, to develop in the lungs and skin.)
Define type 2 respiratory failure.
Type 2 respiratory failure is defined by a low PaO2 (hypoxia) and high PaCO2 (hypercapnia).
Lungs fail to remove CO2 properly.
What are the causes of type 2 respiratory failure?
1) Airway (COPD, Asthma, Sleep apnoea syndrome)
2) Drugs (Suxamethonium- causes short-term paralysis for general anaesthesia)
3) Metabolic (Poisoning, opioid overdose)
4) Neurological (Central - Primary hypoventilation - caused by (1), Head and Cervical spine injury)
5) Muscle – Myasthenia gravis
Define pleural effusion
A pleural effusion is an abnormal collection of fluid in the pleural cavity (potential space between the parietal and visceral pleura)
Exudative = high protein count (>3g/dL)
Transudative = relatively lower protein count (<3g/dL).
Exudative and transudative pleural effusion has seperete causes
Whether it is exudative or transudative helps determine the cause.
What are some causes of exudative pleural effusion
Exudative causes are related to inflammation. The inflammation results in protein leaking out of the tissues into the pleural space, causes include:
1) Lung cancer
2) Pneumonia
3) Rheumatoid arthritis
4) Tuberculosis
What are some causes of transudative pleural effusion?
Transudative causes relate to fluid moving across into the pleural space (trans- meaning moving across). Think of the causes of fluid shifting:
1) Congestive cardiac failure
2) Hypoalbuminaemia
3) Hypothyroidism
What signs and symptoms might a patient with pleural effusion present with?
Symptoms
1) Shortness of breath
2) Cough
3) Pleuritic chest pain: usually associated with an exudate due to pleural irritation
4) Symptoms of the underlying cause, for example:
- Peripheral oedema (heart failure)
- Ascites (liver cirrhosis)
- Productive cough and fever (pneumonia)
Signs:
1) Dullness to percussion: the most accurate positive finding; classically ‘stony dull’
2) Pleural friction rub and bronchial breathing in the most superior aspect of the pleural effusion
What investigations/tests are used to diagnose pleural effusion?
1) 1st line: postero-anterior +/- lateral chest x-ray - findings include:
- Blunting of the costophrenic angles
- Fluid in the lung fissures
- Tracheal and mediastinal deviation (structures shift to one side of chest cavity)
2) Pleural fluid aspiration and analysis - protein count, cell count, pH, glucose, LDH and microbiology testing.
Light’s criteria differentiates between transudative and exudative pleural effusion. It state that an exudate is likely if one or more of the following criteria are met:
- Pleural fluid protein divided by serum protein is > 0.5
- Pleural fluid LDH divided by serum LDH is > 0.6
- Pleural fluid LDH > 2/3 the upper limit of normal serum LDH
Describe the possible results of pleural fluid analysis and what they mean
Pleural fluid analysis: gross appearance
Pale yellow = Transudate (and some exudates)
Heavy blood staining = trauma, malignancy, pulmonary embolism, tuberculosis
Pus - Empyema (pockets of pus)
Food particles - Oesophageal rupture
What is the management plan for pleural effusion?
Non-malignant:
1) Treat the underlying cause: e.g. loop diuretics for congestive heart failure
2) Thoracentesis for symptomatic effusion:
- Needle drainage (thoracocentesis) or chest tube drainage
3) Recurrent effusions:
- Pleurodesis: scarring the pleural space by slurry injection or spraying sterile talc
4) Infective (e.g. sepsis, pneumonia)
- Empirical IV antibiotics
- Diagnostic pleural fluid sampling
- Chest tube drainage as required (e.g. purulent pleural fluid)
Define pneumothorax
A pneumothorax is an abnormal accumulation of air within the pleural space, the space between the parietal and visceral pleura. Collapsed lung!
Types of pneumothorax:
- Spontaneous (primary, secondary)
- Tension
- Traumatic (Iatrogenic, non-iatrogenic)
What are the main causes of tension pneumothorax?
Any pneumothorax (primary spontaneous, secondary spontaneous, traumatic) may result in a tension pneumothorax, a medical emergency - air can enter but cannot leave the pleural space - The accumulated air in the pleural space compresses the lungs, blood vessels, and other structures of the chest cavity.
Most common after traumatic chest injury or in mechanically ventilated patients.
What are the main causes of iatrogenic pneumothorax?
Lung biopsy, mechanical ventilation or central line insertion.
What are the main causes of non-iatrogenic pneumothorax?
Stabbing, chest shotgun wound, impact in traffic accident
What are the main causes of secondary spontaneous pneumothorax?
Lung pathologies such as infection, asthma or COPD
What are the risk factors for developing primary spontaneous pneumothorax?
- Tall, slender, young (aged 20-30)
- Smoking
- Marfan syndrome
- Rheumatoid arthritis
- Family history
- Diving or flying
What is the pathophysiology of primary spontaneous pneumothorax?
Spontaneous rupture of a subpleural bleb/bullae (small/large air spaces in the subpleural space due to air leak from alveoli)
What is the pathophysiology of secondary spontaneous pneumothorax?
Rupture of damaged pulmonary tissue
What is the pathophysiology of tension pneumothorax?
A one-way valve is formed in the pleural space (letting the airflow in but not flow out).
This accumulated air increasing pressure and compresses lungs and heart and shift the trachea.
If pneumothorax compresses the heart, it can reduce diastolic filling and therefore CO
What is the pathophysiology of traumatic pneumothorax?
A penetrating/blunt injury to the chest rips through the parietal pleura allowing air to enter from outside directly into the pleural space
What is the typical presentation of a primary pneumothorax?
A young, tall, healthy male presents with sudden onset breathlessness and chest pain
What is the typical presentation of a secondary pneumothorax?
A middle-aged patient with COPD presents with sudden onset breathlessness and chest pain.
What is the typical presentation of a traumatic pneumothorax?
A middle-aged male presents to the emergency department after being stabbed in the chest with a knife.
What is the typical presentation of a tension pneumothorax?
A mechanically ventilated patient suddenly becomes breathless and haemodynamically unstable.
EMERGENCY
What signs and symptoms might a patient with pneumothorax present with?
Symptoms
1) Sudden-onset pleuritic chest pain
2) Sudden-onset dyspnoea (Shortness of breath)
Signs:
1) Tachycardia and tachypnoea
2) Cyanosis
3) Hyperresonance on percussion
4) Reduced breath sounds on auscultation
What investigations/tests are used to diagnose pneumothorax?
1) CXR: first-line investigation - demonstrates an area between the lung tissue and the chest wall with no lung markings. There will be a line demarcating the edge of the lung where the lung markings end and the pneumothorax begins.
2) In a tension pneumothorax, there is a mediastinal shift (deviation of the mediastinal structures towards one side of the chest cavity) and tracheal deviation contralaterally
3) A repeat CXR is always required following aspiration or drainage to assess efficacy
What is the management plan for pneumothorax?
1) No shortness of breath and less than a 2cm rim of air on the chest x-ray:
No treatment is required as it will spontaneously resolve (follow-up in 2 – 4 weeks)
2) Shortness of breath and/or more than a 2cm rim of air on the chest x-ray:
Aspiration followed by reassessment
When aspiration fails twice, a chest drain is required.
Unstable patients, bilateral or secondary pneumothoraces generally require a chest drain.
What is the safety triangle in a chest drain?
The area where the chest drain needle is inserted, the triangle is formed by:
- The 5th intercostal space (or the inferior nipple line)
- The midaxillary line (or the lateral edge of the latissimus dorsi)
- The anterior axillary line (or the lateral edge of the pectoralis major)
DDx for pneumothorax
- Acute exacerbation of asthma
- Acute exacerbation of COPD
- Pulmonary embolism
Define pulmonary fibrosis - grandma has this :(
Pulmonary fibrosis describes interstitial fibrosis of the lung parenchyma and has several causes. Idiopathic pulmonary fibrosis (IPF) is the most common cause of interstitial fibrosis and has an unknown aetiology, hence the name.
What are the causes of upper zone (lobe) pulmonary fibrosis?
- Coal worker’s pneumoconiosis (black lung disease - caused by inhaling coal dust). Note pneumoconiosis can occur with other types of dust inhaled.
- Silicosis (caused by inhaling silica dust)
- Hypersensitivity pneumonitis (extrinsic allergic alveolitis)
- Ankylosing spondylitis
- Cystic fibrosis
- Sarcoidosis
- Tuberculosis
What are the causes of lower (zone) pulmonary fibrosis?
- Idiopathic pulmonary fibrosis
- Asbestosis
- Drug-induced: amiodarone, methotrexate, Nitrofurantoin (abx for UTI), bleomycin
- Most connective tissue disorders, such as SLE, (excluding ankylosing spondylitis)
- Radiation
What are the risk factors for developing idiopathic pulmonary fibrosis?
- Advanced age: the mean age at diagnosis is 60-70 years of age
- Male gender: twice as common in men
- Smoking
- Family history
- Dust exposure: raising birds, metal, wood, coal, silica
What are the signs and symptoms that a patient with idiopathic pulmonary fibrosis present with?
Symptoms
- Progressive dyspnoea
- Non-productive cough
- Malaise
Signs:
- Bibasal fine end-inspiratory crackles, predominantly in lower zones
- Clubbing
What are the primary investigations used to diagnose idiopathic pulmonary fibrosis?
1) CXR: bilateral reticulonodular opacities (overlapping shadows) mainly affecting the lower zones
2) High-resolution CT thorax: gold standard investigation of choice to confirm the diagnosis, demonstrating increased reticulation and honeycombing (hallmark of pulmonary fibrosis, mainly in the lower zones
3) Spirometry: a restrictive pattern is seen
4) Impaired gas exchange: reduced transfer factor (TLCO)
What are the spirometry results for a restrictive disease (e.g. pulmonary fibrosis)?
FEV1 ↔︎ or ↓
FVC↓↓
FEV1/FVC > 80% normal
What are the signs and symptoms of pneumoconiosis (an upper zone pulmonary fibrosis) - differentiating between LZPF and UZPF is common. exam q
Symptoms
- Exertional dyspnoea
- Dry cough
- Wheezing
- Haemoptysis
- Weight loss
Signs
- Fine crackles
- Wheezing
- Clubbing
What investigations are used to diagnose pneumoconiosis?
CXR: evidence of fibrosis. Nodular opacities (shadows) in the upper zones are classical of silicosis and coal workers’ lungs.
In advanced disease, there is calcification of hilar lymph nodes known as eggshell calcification
Spirometry: typically restrictive pattern with FEV1/FVC > 0.7
What is the management plan for lower pulmonary fibrosis?
Supportive care:
- Pulmonary rehabilitation
- Ambulatory (home) oxygen therapy and/or long-term oxygen therapy
- Vaccinate against pneumococcus and influenza
Anti-fibrotic agents:
Pirfenidone or nintedanib if FVC is 50% - 80% of predicted.
Lung transplantation if no contraindications and tolerated.
What is the treatment/management for pneumoconiosis (upper zone pulmonary fibrosis)?
Non-curable and largely conservative - patients might be eligible for legal compensation
- Smoking cessation and avoidance of exposure
- Pulmonary rehabilitation
- Supplementary oxygen: hypoxic patients may benefit from long term or ambulatory oxygen
- Lung transplantation: used in refractory end-stage disease
Define sarcoidosis
Sarcoidosis is an inflammatory condition defined by non-caseating granulomas, which are small patches of red and swollen tissue. It is a multi-systemic disease in which any organ can be affected, although the lungs, skin and eyes are mainly affected.
What is the pathophysiology of sarcoidosis?
Although the aetiology is unknown, it is thought to be due to a type IV hypersensitivity reaction against an unknown antigen.
A T-cell-mediated immune response to an antigenic stimulus causes the formation of granulomas, in which macrophages begin to release local mediators that result in inflammation.
What are the risk factors for developing sarcoidosis?
1) Afro-Caribbean and Scandinavian ethnicity
2) Young adults: commonly presents at 20-40 years of age
3) Female gender
4) Family history
What signs and symptoms might a patient with sarcoidosis present with?
Acute sarcoidosis = swinging fever, polyarthralgia and erythema nodosum (painful red, round lumps typically appearing on the shins and ankles).
In contrast insidious sarcoidosis = non-productive cough, dyspnoea and fatigue
Symptoms
1) Cough: non-productive
2) Polyarthralgia (multi-joint pain)
3) Uveitis - red-eye, photophobia
4) Constitutional symptoms: swinging fever, fatigue, weight loss
5) Dyspnoea: gradual onset
Signs
1) Cervical and submandibular lymphadenopathy (swelling of lymph nodes)
2) Erythema nodosum: dusky-coloured nodules on the shins
What is Lofgren’s syndrome?
An acute form of sarcoidosis associated with migratory polyarthritis, erythema nodosum, fever, and bilateral hilar lymphadenopathy.
Good prongosis
What investigations/tests are used to diagnose sarcoidosis?
Clinical diagnosis mainly as there is no single diagnostic test.
Primary Investigations:
1) CXR: first-line imaging; may show hilar lymphadenopathy or bilateral infiltrates
2_ Routine bloods: inflammatory markers may be raised and can screen for other organ involvement, e.g. renal function
3) Serum calcium: hypercalcaemia (10%); non-caseating granulomas consist of activated macrophages which have 1-alpha-hydroxylase activity and activate vitamin D
CXR findings in sarcoidosis can be divided into 4 stages. What do the results in each stage look like?
Stage 0 - Normal
Stage I - Bilateral hilar lymphadenopathy
Stage II - Bilateral hilar lymphadenopathy and interstitial infiltrates
Stage III - Diffuse pulmonary infiltrates without hilar lymphadenopathy.
Stage IV - Diffuse fibrosis
DDx for sarcoidosis
- TB
- Non-small cell lung cancer
- Hodgekin’s lymphoma
- Non-Hodgekin’s lymphoma
What are the management plans for sarcoidosis?
Main treatment = observation or steroids
1) Indications for steroids:
- Symptomatic and stage 2 or 3 on chest X-ray (no treatments needed if milder)
- Extrapulmonary involvement e.g. ocular, neurological or cardiac disease
- Hypercalcaemia
2) Pulmonary disease:
- Asymptomatic non-progressive disease > observation
- Symptomatic or progressive disease:
1st line: corticosteroids, oral prednisolone mainstay, inhaled budesonide
3) Extrapulmonary disease:
1st line: corticosteroids
Define pulmonary hypertension
Pulmonary hypertension is a mean pulmonary arterial pressure (mPAP) greater than 20 mmHg at rest.
It can be primary or secondary to an underlying cause
What is the aetiology of pulmonary hypertension?
The causes of pulmonary hypertension
1) Group 1 – Primary pulmonary hypertension or connective tissue disease such as systemic lupus erythematous (SLE)
2) Group 2 – Heart failure usually due to myocardial infarction or systemic hypertension
3) Group 3 – Chronic lung disease such as COPD
4) Group 4 – Pulmonary vascular disease such as pulmonary embolism
5) Group 5 – Miscellaneous causes such as sarcoidosis, glycogen storage disease and haematological disorders
What is the pathophysiology of pulmonary hypertension?
The underlying pathology increases resistance in the pulmonary vasculature leading to increased pressure in the right ventricle.
This results in increased ventricular filling and stroke volume, which further increases pulmonary arterial pressure.
Over time, right ventricular hypertrophy develops, which causes increased pulmonary pressure
What is the most common cause of secondary pulmonary hypertension?
COPD
What investigations/tests are used to diagnose pulmonary hypertension?
1st line: ECG - provides evidence of pulmonary hypertension, with right-sided abnormalities:
- Right ventricular hypertrophy, right axis deviation, right atrial enlargement
2) Echocardiogram (ECHO): to assess right ventricular function and estimate pulmonary arterial pressures.
3) Chest x-ray - changes include dilated pulmonary arteries and right ventricular hypertrophy
4) Pulmonary function tests: to investigate for other causes of breathlessness
Right heart catheterisation: gold-standard and diagnostic test to directly measure the pulmonary pressure
What is the management plan for pulmonary hypertension?
The treatment options below refer to the management of PAH (WHO group 1).
First-line:
1) Calcium channel blockers: e.g. nifedipine and diltiazem
2) Pulmonary vasodilators (if no response to CCB)
- IV prostanoids (e.g. epoprostenol)
- Endothelin receptor antagonists (e.g. macitentan)
- Phosphodiesterase-5 inhibitors (e.g. sildenafil)
3) Diuretics: for right ventricular failure and overload
4) Oxygen therapy: if PO2 is consistently less than 60mmHg
5) Consider anticoagulation: with warfarin or a novel oral anticoagulant (NOAC)
Define lung cancer
The majority of lung cancers are primary bronchial carcinomas. Lung cancers are categorised into small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).
What is small-cell lung cancer (SCLC)?
1) 15% of lung cancer cases
2) Derived from neuroendocrine Kulchitsky cells (APUD cells)*
3) Rapid growth and patients usually present in an advanced stage
4) Central lung lesions
APUD:
A - Amine: high amine content
PU - Precursor Uptake: high uptake of amine precursors (such as 5-HTP)
D - Decarboxylase: high content of the enzyme decarboxylase
What is non-small-cell lung cancer (NSCLC)?
- 85% of lung cancer cases
Composed of:
- Squamous cell (25 - 30%) - associated with smoking
- Adenocarcinoma (40%) - mostly non-smokers
- Large-cell (10 - 15%)
- Carcinoid tumours
NSCLC: what is a lung adenocarcinoma?
1) Most common primary lung cancer (40% of NSCLC)
2) Most common cell type in non-smokers
3) Originate from mucus-secreting glandular cells
4) Peripheral lung lesions
Do large-cell NSCLCs have central or peripheral lesions?
Peripheral
NSCLC: what is squamous cell NSCLC?
1) MOST strongly associated with cigarette smoking
2) Arises from epithelial cells typically in the central bronchus
3) Central lung lesions
What do SCLCs release?
They contain neurosecretory granules that release neuroendocrine hormones leading to paraneoplastic syndrome
What paraneoplastic syndrome can ectopic anti-diuretic hormone (ADH) secretion by SCLCs cause?
- Syndrome of inappropriate ADH (SIADH). It presents with hyponatraemia.
What paraneoplastic syndrome can ectopic adrenocorticotropic hormone (ACTH) secretion by SCLC cause?
Cushing’s syndrome
What paraneoplastic syndrome can ectopic parathyroid hormone secretion by NSCLC squamous cell carcinoma cause?
Hypercalcaemia
What is Lambert-Eaton myasthenic syndrome?
A paraneoplastic syndrome associated with SCLCs.
The immune system produces antibodies against SCLC cells, which target and damage voltage-gated calcium channels on presynaptic terminals in motor neurones.
Leading to weakness in:
- Proximal muscles
- Intraocular muscles > diplopia
- Levator muscles > ptosis
- Pharyngeal muscles causing slurred speech and dysphagia (difficulty swallowing)
Patients may also experience dry mouth, blurred vision, impotence and dizziness due to autonomic dysfunction.
What are the risk factors for developing lung cancer?
1) Increasing age: adenocarcinomas are an exception, often occurring in younger patients
2) Smoking: tobacco smoking or environmental smoke exposure - associated strongly with SCLCs, squamous cell and large-cell NSCLC
Other environmental exposure: radon, asbestos, arsenic, chromium and radiation
Family history
What signs and symptoms might a patient with lung cancer present with?
Symptoms
1) Persistent cough +/- haemoptysis
2) Dyspnoea
3) Pleuritic chest pain
4) Constitutional symptoms:
- Fever
- Weight loss and anorexia
- Night sweats
- Lethargy
Signs
1) Reduced breath sounds and +/- a fixed monophonic wheeze
2) Stony dull percussion: suggests a malignant pleural effusion
3) Supraclavicular or persistent cervical lymphadenopathy
4) Extrapulmonary manifestations:
- Clubbing: strongly associated with squamous cell carcinoma
- Facial plethora and swelling: due to superior vena cava obstruction (SVCO)
- Hoarseness: due to recurrent laryngeal nerve palsy (Pancoast tumour)
- Horner’s syndrome - triad of partial ptosis, anhidrosis (absence of sweat) and miosis (pupil constriction). Caused by a Pancoast tumour (tumour in the pulmonary apex) pressing on the sympathetic ganglion.
What are some symptoms of metastatic lung cancer?
1) Bone pain
2) Headache, seizures, neuro deficit
3) Abdominal pain
What are the investigations/tests used to diagnose lung cancer?
1) 1st line: chest X-ray: hilar enlargement, consolidation, pleural effusion, or circular opacity. Normal in ~10% of patients with lung cancer
2) CT chest with contrast: gold-standard - if abnormal CXR or persistent symptoms with normal CXR (particularly in smokers)
3) Diagnostic - biopsy
Secondary lung cancer is caused by metastasis from another part of the body. What are the most common sites where cancer to the lungs can spread from?
3B KP
Breast
Bowel
Bladder
Kidney
Prostate
Secondary lung cancer is more common than primary lung cancer
What is the management plan for SCLC?
1) All patients
- Smoking cessation
2) SCLC: late presentation and often have advanced or metastatic disease
- Localised disease (confined to ipsilateral hemithorax): chemoradiotherapy with platinum-based agents, e.g. cisplatin
- Surgery is only appropriate for patients with early disease (T1-2a, N0, M0)
- Advanced or metastatic disease: chemoradiotherapy with platinum-based agents, or palliative chemotherapy
What is the management plan for NSCLC?
1) All patients:
- Smoking cessation
2) Non-metastatic disease (stage I-IIIa):
- Surgery, usually with adjuvant chemotherapy
e.g. Segmentectomy or wedge resection involves taking a segment or wedge of lung (a portion of one lobe), lobectomy or pneumonectomy
3) Curative radical radiotherapy can be used as an alternative to surgery
4) Metastatic disease (stage IIIb and above):
- Palliative treatment with immunotherapy, chemotherapy, and radiotherapy
- Remember, NSCLC generally has a poor response to chemotherapy
Define mesothelioma
Lung malignancy that affects the mesothelial cells of the pleura. It is strongly linked to asbestos inhalation.
Short-term exposure to asbestos can result in mesothelioma.
There is a huge latent period between exposure to asbestos and the development of mesothelioma between 20 - 40 years.
What is the pathophysiology of mesothelioma caused by asbestos?
Asbestos is believed to result in macrophage and neutrophil activation, consequently generating reactive oxygen and nitrogen species. This chronic inflammation causes DNA damage and modifications in gene expression. thus increasing the risk of cancer.
What signs and symptoms might a patient with mesothelioma present with?
History of exposure to asbestos (85% cases)
Pre-existing diagnosis of asbestosis (20% cases)
Painless unilateral pleural effusion (30% cases)
Symptoms
- Shortness of breath
- Cough
- Pleuritic chest pain or chest wall pain
- Constitutional symptoms: fatigue, fever, night sweats, weight loss
Signs:
- Reduced breath sounds
- Stony dull percussion: suggests a pleural effusion
- Ascites: if peritoneal disease is present
- Finger clubbing
What investigations/tests are used to diagnose mesothelioma?
1st line
- CXR: unilateral pleural effusion, reduced lung volumes, pleural thickening, lower zone interstitial fibrosis for asbestos
- Contrast-enhanced CT chest: performed following a suspicious CXR and may demonstrate pleural thickening, pleural plaques and enlarged lymph nodes
What is the management plan for mesothelioma - operable?
By the time mesothelioma is diagnosed, it has often metastasised, the prognosis is very poor. Chemotherapy can improve survival, but it is essentially palliative.
Treatment options divided into operable and inoperable
1) Operable: surgery
- Extrapleural pneumonectomy
- Pleurectomy with decortication (removal of fibrous tissue)
- Rarely curative
+/- Chemotherapy agents include cisplatin
+/- Radiotherapy
What is the management plan for inoperable mesothelioma?
Palliative chemotherapy, agents include cisplatin and pemetrexed
+/- Radiotherapy
Define hypersensitivity pneumonitis
Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, results from non-IgE mediated immunological inflammation.
HP is caused by repeated inhalation of non-human protein from plants or animals or can result from a chemical conjugated to albumin in the airways.
Affects the alveoli and distal bronchioles
What are the aetiology/risk factors for developing hypersensitivity pneumonitis?
- Smoking
- Viral infection
- Exposure to avian protein (bird fancier’s lung), mould (farmer’s lung) or bacterial antigen
- Exposure to diisocyanate (e.g., epoxy resin)
or metalworking fluid - Drug-induced: nitrofurantoin (Abx), methotrexate (immunosuppressant), roxithromycin (Abx), and rituximab (mAb)
What signs and symptoms might a patient with hypersensitivity pneumonitis present with?
Symptoms:
- Dyspnoea
- Cough
- Constitutional symptoms: fever/chills, malaise, weight loss/anorexia
Signs:
- Diffuse, bibasilar rales ( bubbling or crackling sound originating from the base of the lungs)
- Clubbing
What investigations/tests are used to diagnose hypersensitivity pneumonitis?
1) 1st line: CXR - infiltrates, nodular or patchy; fibrosis
2) CT chest - ground-glass shadowing and poor-defined micronodules. More accurate than CXR - differentiates between fibrotic and non-fibrotic HP
3) Serum IgG - positive
4) Pulmonary function test. -restrictive or mixed obstructive/restrictive picture
What is the management plan for hypersensitivity pneumonitis?
1st line: avoidance of antigen
2) Smoking cessation
3) Pulmonary rehabilitation programmes to improve their functional status and quality of life.
4) Supplemental oxygen - severe hypoxaemia (PaO₂ ≤55 mmHg or oxygen saturation ≤89%) at rest or with exertion
5) Corticosteroid - for persistent acute symptoms despite avoidance of antigen; moderate to severe respiratory impairment and/or extensive lung involvement on imaging.
- Patients with fibrotic HP = long-term, low-dose corticosteroid therapy.
- Patients with inflammatory features are more likely to benefit from this treatment.
Define dyspnoea
Dyspnoea, also known as shortness of breath or breathlessness, is a subjective sensation of breathing discomfort. It is a common symptom
What are the main aetiologies of dyspnoea?
Acute:
- Asthma
- COPD
- Heart failure
- Pneumonia (or other infection)
Chronic (>1month):
- Pulmonary disease
- Cardiovascular disease
- Respiratory muscle dysfunction
- Psychogenic dyspnoea
- Obesity.
What is the MRC dyspnoea scale?
A scale that allows patients to indicate the extent to which their breathlessness affects their mobility.
Grade 1: Not troubled by breathlessness except on strenuous exercise
Grade 2: the patient is out of breath when walking up a slight hill or hurrying
Grade 3: patient has to walk slower than people of same age on level ground because of breathlessness, or has to stop for breath when walking at own pace
Grade 4: Stops for breath after walking about 100 metres or after a few minutes on level ground
Grade 5: Too breathless to leave the house, or breathless when dressing or undressing
Define interstitial lung disease
Interstitial lung disease is an umbrella term to describe conditions that affect the lung parenchyma (tissue) causing inflammation and fibrosis. Fibrosis involves the replacement of the normal elastic and functional lung tissue with scar tissue that is stiff and does not function effectively. ILD includes:
- Idiopathic pulmonary fibrosis
- Drug-induced pulmonary fibrosis
- Secondary pulmonary fibrosis (caused by A1AT deficiency, RA, SLE etc.)
- Cryptogenic Organising Pneumonia
- Asbestosis
- Hypersensitivity Pneumonitis (AKA Extrinsic Allergic Alveolitis)
What are the main medications that can cause drug-induced pulmonary fibrosis?
- Amiodarone (arrhythmia)
- Cyclophosphamide (RA)
- Methotrexate (Crohn’s)
- Nitrofurantoin (Abx)
What are some specific causes of hypersensitivity pneumonitis?
Bird-fanciers lungis a reaction to bird droppings
Farmers lungis a reaction to mouldy spores in hay
Mushroom workers’ lungis a reaction to specific mushroom antigens
Malt workers lungis a reaction to mould on barley
What is cryptogenic organising pneumonia? Grandma has this :(
Cryptogenic organising pneumonia involves a focal area of inflammation of the lung tissue. This can be idiopathic or triggered by infection, inflammatory disorders, medications, radiation or environmental toxins or allergens.
What signs and symptoms might a patient with cryptogenic organising pneumonia present with?
Presentation is very similar to infectious pneumonia with shortness of breath, cough, fever and lethargy. It also presents on similarly to pneumonia on a chest xray with a focal consolidation.
What is the definitive investigation for cryptogenic organising pneumonia?
Lung biopsy
What is the treatment for cryptogenic organising pneumonia?
Treatment is with systemic corticosteroids - most commonly used prednisolone.
Define asbestosis
Restrictive lung disease due to interstitial fibrosis after asbestos exposure
The lower zones are predominantly affected.
Severity is related to the length of exposure, with a latent period of 15-30 years
How might a patient with asbestosis present?
Patients usually present with dyspnoea and reduced exercise tolerance.
What investigations/tests are used to diagnose asbestosis?
1st line: CXR posteroanterior and lateral - lower zone linear interstitial fibrosis; progressively involves the entire lung; pleural thickening
Pulmonary function test: restrictive changes; may have obstructive picture (especially if history of asbestos exposure and smoking)
What is the management plan for asbestosis?
1st line: smoking cessation and advice
- Abx if symptoms of infection
- Patients with obstructive airways
disease > bronchodilation therapy - Pulmonary rehabilitation is designed to reduce symptoms and optimise functional status
Ipratropium
1) Use
2) MOA
3) Side effects
1) Reversible bronchial obstruction (COPD)
2) Acetylcholine antagonist by blocking muscarinic cholinergic receptors.
3) Arrhythmias; constipation; cough
What are some causes of occupational asthma?
- Isocyanates (chemicals often found in spray paint)
- Flour and grain dust (baker)
- Latex (nurses)
- Animals (lab techs, farmers)
- Wood dust (timber workers)
DDx for cystic fibrosis
- Asthma
- GORD
DDx for community-acquired pneumonia
- COVID-19
- Acute bronchitis
- COPD/asthma excerbation
DDx of hospital-acquired pneumonia
- COVID-19
- Cardiogenic pulmonary oedema as a complication of congestive HF
- Acute respiratory distress syndrome
DDx for non-small cell lung cancer
- Small cell lung cancer
- Metastatic lung cancer
DDx for small cell lung cancer
- Non-small cell lung cancer
- Pneumonia/bronchitis
DDx for hypersensitivity pneumonitis
- VIral pneumonia
- Sarcoidosis
