RESPIRATORY MEDICINE

What are the 4 mechanisms by which pathogens causing pneumonia gain access to the lungs?

Inhalation

Aspiration of gastric contents

Haematogenous spread from a distant focus

Direct spread from an adjacent infected organ

What is the treatment regimen for TB meningitis in Malawi?

• 2RHZE/7RH

How does chronic bronchitis cause airflow obstruction?

• ↑ mucus production + ↓ ciliary clearance + airway inflammation/remodelling → airway narrowing → airflow obstruction

What is the GOLD 2023 definition of COPD?

• GOLD 2023 defines COPD as a heterogeneous lung condition characterized by chronic respiratory symptoms (dyspnea, cough, expectoration, and/or exacerbations) due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction

When is a pleural effusion an exudate by Light's criteria?

• Pleural fluid protein / serum protein ≥0.5

• Pleural fluid LDH / serum LDH >0.6

• Pleural fluid LDH >2/3 the upper limit of normal serum LDH

How does emphysema cause airflow obstruction?

• Alveolar wall destruction → ↓ elastic recoil → small-airway collapse during expiration → air trapping + hyperinflation

When is Light's criteria used in pleural effusion?

• When pleural fluid protein is between 25 and 35 g/L, where it is difficult to distinguish a transudate from an exudate

What are the ECG signs of right ventricular strain/cor pulmonale?

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• Right axis deviation

• Right ventricular hypertrophy:
  • Tall R wave in V1 >7 mm = >7 small boxes
  • R/S ratio >1 in V1
  • Deep S wave in V5–V6 >7 mm = >7 small boxes

• Right atrial enlargement:
  • P pulmonale = tall, peaked P waves in II, III and aVF
  • P-wave amplitude >2.5 mm = >2½ small boxes

• Right ventricular strain:
  • ST depression + T-wave inversion in V1–V3, sometimes extending to V4
  • May also occur in the inferior leads

What is sarcoidosis?

A multisystem granulomatous disorder of unknown cause

What are the typical demographics of sarcoidosis?

• Usually adults aged 20-40 years

• More common in women

• More frequent and severe in people of African ancestry

Why is African ancestry a risk factor for HIV-associated nephropathy?

Higher frequency of APOL1 risk variants
G1 and G2 variants increase susceptibility to HIV-associated kidney disease
HIV + APOL1 risk variants → podocyte injury → collapsing FSGS

What important conditions can cause secondary spontaneous pneumothorax?

• Tuberculosis

• PCP

• Necrotising pneumonia

• Pulmonary Langerhans cell histiocytosis

• Lymphangioleiomyomatosis

• Birt-Hogg-Dubé syndrome

• Marfan syndrome

• Ehlers-Danlos syndrome

What is the creatinine clearance cutoff for modifying ethambutol and pyrazinamide dosing?

• Creatinine clearance <50 mL/min

What should be done with streptomycin in renal failure?

• Avoid it if possible

• If essential, reduce the dosing frequency

According to the Malawi TB guidelines, when should significant TB drug-induced liver injury be discussed with the National TB Programme?

• ALT >200 IU/L and/or total bilirubin >3 mg/dL

What are the main causes of restrictive lung disease?

• Pleural effusion

• Pneumoconiosis eg silicosis, coal lung

• Lung fibrosis

• Chest wall diseases

• Guillain Barre syndrome

• Myasthenia gravis

• Obesity

• Pneumonectomy

• Lobectomy

What are the differentials of pleural fluid with strands?

• Tuberculosis

• Parapneumonic effusion

• Empyema

• Malignancy

• Haemothorax

• Rheumatoid arthritis

• Systemic lupus erythematosus

What is the liver-sparing TB regimen when using the Malawi guideline doses?

• Levofloxacin 15–20 mg/kg daily, maximum 1000 mg

• Ethambutol 800–1200 mg daily

• Linezolid 600 mg daily

When can isoniazid, rifampicin and pyrazinamide be reintroduced after liver toxicity?

• When ALT falls below 100 U/L and bilirubin is normal

• Reintroduce them stepwise

What is the treatment of massive haemoptysis due to aspergillosis?

• Suppress cough with morphine and codeine

• Transfuse if needed

• Amphotericin B for 6–12 weeks OR Voriconazole for 6–12 weeks OR Itraconazole for 6–12 weeks

• Lobectomy

What pathogen causes an aspergillosis?

• Aspergillus fumigatus

How does an aspergillosis appear on chest X-ray?

• A rounded mass within a pre-existing lung cavity

• An air crescent is seen around the fungal ball

• The fungal ball may move with changes in position

When are corticosteroids used in tuberculosis?

• TB meningitis

• TB pericarditis

• TB adrenalitis with adrenal insufficiency

• TB iritis/ uveitis

When should linezolid be avoided in the liver-sparing TB regimen?

• Haemoglobin <8 g/dL

What alternative can be considered if liver-sparing drugs are contraindicated or unavailable?

• Cycloserine

Which first-line TB drugs are hepatotoxic?

• Isoniazid

• Rifampicin

• Pyrazinamide

  
  

What investigations are done when TB drug-induced liver toxicity is suspected?

• Liver function tests

• HBsAg

• Liver ultrasound

What are the main defence mechanisms of the airway against inhaled particles?

• Nose and trachea

Warms and humidifies air

Traps almost all particles >10 µm in diameter

• Mucocilliary escalator

The airway is lined by mucus producing cells

This disposes off particles 2-10 µm in diameter

• Alveolar macrophages

Phagocytose particles around 2 µm

Particles < 2 µm are not phagocytosed – they are exhaled

In which three ways is pneumonia classified?

By site of infection

• Lobar pneumonia

• Bronchopneumonia

By aetiology – Typical/ Atypical

• Bacterial

• Viral

• Fungal

• Protozoal

• Others

By location of disease acquisition

• Community acquired pneumonia

• Nosocomial pneumonia – formerly called health care associated pneumonia

  • Hospital acquired pneumonia - pneumonia acquired ≥48 hours after hospital admission.

  • Ventilator associated pneumonia - pneumonia acquired ≥48 hours after endotracheal intubation

What is the characteristic radiological/pathological finding in lobar pneumonia?

Diffuse consolidation of the affected lobe

Where can the inflammation extend in lobar pneumonia?

To the pleura or to a major fissure

What is the classic causative organism of lobar pneumonia?

Streptococcus pneumoniae

Does lobar pneumonia usually affect one or both lungs?

Usually one lung

What are the four stages of lobar pneumonia?

• Congestion

• Red hepatisation

• Grey hepatisation

• Resolution

  
  

What happens during the congestion stage of lobar pneumonia?

The lung becomes heavy, red and boggy due to vascular congestion, with proteinaceous alveolar fluid, polymorphonuclear cells and bacteria filling the alveoli.

What happens during red hepatisation?

The alveolar spaces become packed with neutrophils, red blood cells and fibrin, causing the lung to become firm with a liver-like consistency.

What happens during grey hepatisation?

Red blood cells undergo lysis while fibrinous exudate persists. The lung remains firm with a liver-like consistency.

What happens during resolution of lobar pneumonia?

Oedema resolves and the inflammatory debris becomes granular/semi-fluid. A few macrophages persist, the lung becomes aerated again and its texture returns toward normal. In untreated cases, this takes about 8–10 days; severe cases may heal with scarring.

What is bronchopneumonia?

Focal inflammation centred on the airways, with consolidation occurring around the bronchioles.

How does the pattern of consolidation in bronchopneumonia differ from lobar pneumonia?

Bronchopneumonia has patchy/focal consolidation around the bronchioles, whereas lobar pneumonia has diffuse consolidation of an entire lobe.

Which areas of the lungs are commonly affected in bronchopneumonia?

It commonly affects the lower lobes.

Does bronchopneumonia commonly affect on or both lungs?

It is often bilateral.

How does bronchopneumonia differ from lobar pneumonia in distribution?

Bronchopneumonia is often bilateral and patchy, whereas lobar pneumonia is usually unilateral and restricted to one lobe.

In which type of patient is bronchopneumonia particularly common?

It is common in debilitated patients.

What are the typical bacterial causes of pneumonia?

• Streptococcus pneumoniae

• Moraxella catarrhalis

• Haemophilus influenzae

• Staphylococcus aureus

• Klebsiella pneumoniae

• Escherichia coli

• Pseudomonas aeruginosa

• Microaerophilic bacteria

• Anaerobes

Which bacteria are more commonly associated with pneumonia in patients with COPD?

Haemophilus influenzae and Moraxella catarrhalis.

Which organism causes cavitating pneumonia and is often associated with recent influenza?

Staphylococcus aureus. Evidence of recent influenza is present in about 40–50% of patients.

Which organism causes cavitating pneumonia and is associated with alcoholism?

Klebsiella pneumoniae.

Which organisms can cause pneumonia and are associated with aspiration?

Microaerophilic bacteria and anaerobes.

What is atypical pneumonia?

Pneumonia caused by bacteria that are intrinsically resistant to beta-lactam antibiotics and cannot be visualized on Gram stain or cultured using traditional techniques.

Which organisms cause atypical pneumonia?

• Legionella spp.

• Mycoplasma pneumoniae

• Chlamydia pneumoniae

• Chlamydia psittaci

• Coxiella burnetii

How is Legionella pneumonia acquired?

By inhaling water droplets or mist containing the bacteria, for example from contaminated air-conditioning systems.

Which atypical pneumonia is particularly associated with young people?

Mycoplasma pneumoniae.

How often does Mycoplasma pneumoniae pneumonia occur in cycles?

Every 3–4 years.

What is characteristic about Mycoplasma pneumoniae infection?

Prominent extrapulmonary symptoms.

How is Chlamydia psittaci pneumonia acquired?

Through exposure to infected birds.

What important condition is Coxiella burnetii associated with?

Culture-negative endocarditis.

Give the major extrapulmonary manifestations of Mycoplasma pneumoniae.

Skin: erythema multiforme and other rashes
Nervous system: encephalitis, meningitis, peripheral neuropathy
Blood: haemolytic anaemia
Musculoskeletal: arthralgia and arthritis
Cardiac: myocarditis and pericarditis
ENT: otitis media

List the viral causes of pneumonia

• Influenza

• Respiratory syncytial virus (RSV)

• Cytomegalovirus (CMV)

• Human metapneumovirus
  
  

List the fungal/protozoal causes of pneumonia

• Pneumocystis jirovecii pneumonia (PJP/PCP)

• Cryptococcus

• Candida

• Nocardia

• Aspergillus

• What are the key features of Streptococcus pneumoniae?

Gram-positive diplococcus
Alpha-haemolytic
Thick-walled and capsulated

How many serotypes of Streptococcus pneumoniae are there?

More than 85 serotypes.

What is Streptococcus pneumoniae highly associated with?

HIV infection

What proportion of all childhood deaths is attributed to Streptococcus pneumoniae?

About 11%

What infections can Streptococcus pneumoniae cause?

Otitis media, sinusitis, pneumonia, meningitis, pericarditis, peritonitis and septic arthritis.

List the common organisms causing community-acquired pneumonia.

• Streptococcus pneumoniae

• Haemophilus influenzae

• Mycobacterium tuberculosis

• Respiratory syncytial virus (RSV)

• Pneumocystis jirovecii pneumonia (PJP)

List the common organisms causing nosocomial pneumonia.

• Viruses: RSV

• Gram-negative: E. coli, Klebsiella, Pseudomonas

• Gram-positive: Staphylococcus aureus, Staphylococcus epidermidis

• Mycobacterium tuberculosis

What is an important characteristic of organisms causing nosocomial pneumonia?

They are often multidrug-resistant.

What investigations are done in pneumonia?

• HIV test

• FBC

• U&Es

• Blood culture

• Sputum analysis

• Chest X-ray

• Blood gases

• Respiratory swab

• Urinary antigen tests

• BAL sample when indicated

What tests can be performed on sputum in suspected pneumonia?

• Gram stain

• ZN stain

• Culture and sensitivity

• Xpert MTB/RIF

What can respiratory swabs detect in pneumonia?

Mycoplasma pneumoniae and respiratory viruses by PCR.

What urinary antigen tests can be used in pneumonia?

Legionella and pneumococcal urinary antigen tests.

What test can be used to investigate Pneumocystis jirovecii pneumonia (PJP) from a BAL sample?

Silver staining

How does counter-immunoelectrophoresis compare with sputum or blood culture for detecting Streptococcus pneumoniae?

It is 3-4 times more sensitive.

What are the five criteria of the CURB-65 score?

C: Confusion, abbreviated mental test score <8/10
U: Urea >7 mmol/L (BUN >20 mg/dL)
R: Respiratory rate >30 breaths/min
B: Systolic BP <90 mmHg or diastolic BP <60 mmHg
65: Age >65 years

How is the CURB-65 score interpreted?

0-1: Treat as an outpatient
2: Admit to hospital
3+: Often requires intensive treatment unit (ITU) care

What other severity scores are used for pneumonia?

• CRB score

• Pneumonia Severity Index (PSI)

When is the CRB score used?

To assess pneumonia severity in the community when urea cannot be measured.

What is the Pneumonia Severity Index (PSI) used for?

To assess the severity and risk of mortality in community-acquired pneumonia.

Why has CURB-65 not been validated in patients with HIV?

Because HIV can alter the organisms causing pneumonia, disease presentation and prognosis, while CURB-65 does not account for HIV-specific factors such as immunosuppression or CD4 count.

What are the general complications of pneumonia?

• Respiratory failure

• Sepsis with multisystem failure

What are the local complications of pneumonia?

• Pleural effusion

• Empyema

• Lung abscess

• Organising pneumonia

What are the three main groups of risk factors for pneumonia?

• Decreased systemic resistance of the host

• Impaired local defence mechanisms

• Impaired alveolar macrophage function

What are examples of factors that decrease systemic resistance of the host?

• Chronic diseases

• HIV

• Immunosuppressive drugs, e.g. steroids and chemotherapy

• Leukopenia

What are examples of factors that impair local defence mechanisms?

• Loss or suppression of the cough reflex

• Anaesthesia

• Neuromuscular disorders

• Convulsions

• Mucociliary dysfunction

• Accumulation of secretions

• Cystic fibrosis

• Bronchiectasis

What are examples of factors that impair alveolar macrophage function?

• Alcohol

• Tobacco smoke

• Anoxia

• Pulmonary congestion or oedema

What is the pathophysiology of pneumonia?

Pathogen enters alveoli → alveolar macrophages recognise the pathogen → macrophages release cytokines → IL-1 and TNF-α cause vasodilation and increased vascular permeability → fluid moves from alveolar capillaries into the alveoli, causing congestion → IL-8 attracts neutrophils into the alveoli to help control the infection.

What is unusual about Pneumocystis jirovecii?

It is an ascomycetous fungus that cannot be treated with conventional antifungal drugs and was previously classified as a protozoan.

What type of immune defect is most strongly associated with Pneumocystis pneumonia?

Abnormalities in T-lymphocyte function or number, particularly CD4+ T lymphocyte deficiency.

Which patients are particularly at risk of developing PJP?

• People living with HIV, especially CD4 <200 cells/µL

• Patients receiving prolonged/ high-dose corticosteroids

• Patients receiving other significant immunosuppression

• Certain cancer patients receiving chemotherapy or T-cell-depleting therapy

• Transplant recipients

• Patients with primary immunodeficiency

• Patients with idiopathic CD4 lymphocytopenia

In HIV, when is PCP prophylaxis indicated?

• CD4 <200 cells/µL

• Previous episode of PJP

• Oropharyngeal candidiasis, according to the guideline in your notes

What is the pathogenesis of PCP?

The organism is inhaled → reaches the alveoli → attaches to type I pneumocytes → is normally cleared by host defences → in immunodeficiency it persists and proliferates → causes diffuse pulmonary injury and impaired gas exchange

What are the two morphological forms of Pneumocystis?

• Cystic forms

• Trophic forms

What is the first-line treatment for PCP?

• Admit and give oxygen

• Cotrimoxazole 120mg/kg/day, divided into 3 doses (8-hourly) for 21 days

• Lifelong maintenance (CPT)

• Prednisolone (Give 15-30 minutes before cotrimoxazole)

• 8 tablets 12-hourly for 5 days, then

• 8 tablet 24-hourly for 5 days, then

• 4 tablets 24-hourly for 11 days

When should IV cotrimoxazole be considered?

When the patient cannot swallow and enteral administration via an NG tube is not possible

When are corticosteroids added to PCP treatment?

When there is significant hypoxaemia or respiratory distress

Why are corticosteroids useful in severe PCP?

They reduce the inflammatory response and pulmonary injury that can worsen gas exchange when treatment begins

What is the second-line treatment for PCP?

• Clindamycin 600mg 8-hourly for 21 days + Primaquine 30mg 24-hourly for 21 days

• Dapsone + trimethoprim

• Atovaquone

• Parenteral pentamidine

• Caspofungin

• Nebulized pentamidine

What stains can be used to demonstrate Pneumocystis?

• Stain the wall of the cystic form

  • Methenamine silver

  • Toluidine blue O

  • Cresyl violet

• Stain the nuclei of both trophic and cystic forms

  • Diff-Quik

  • Wright-Giemsa