Alveolar-arterial gradient (A-a gradient)

Calculated A-a gradient = 150mmHg - PaCO2/0.8 - PaO2
Expected A-a gradient = Age/4 + 4


Normal A-a gradient suggest hypoventilation (hypoxia proportional to low ventilatory effort)
Increased A-a gradient suggest defect in diffusion, V/Q mismatch or right-left shunt

CURB-65 scoring

Sarcoidosis

- multisystem granulomatous disorder of unknown cause
- prevalence highest in Northern Europe
- 20-40% asymptomatic, discovered incidentally after routine CXR
- acute sarcoidosis presents with erythema nodosum and polyarthralgia which resolves spontaneously
- serum ACE elevated in 60% of patients, presumably reflecting macrophage activity
- transbronchial biopsy provide positive histology in 80% of patients
- Kveim reaction, a granulomatous reaction appearing 4 weeks after intradermal injection of sarcoid spleen or lymph node extract is positive in 50-60% of patients
- Mikulicz syndrome : sarcoidosis with parotid gland enlargement
- Heerfordt's syndrome (uveoparotid fever) : Mikulicz syndrome with acute uveitis and facial nerve palsy

Asbestosis

- caused by inhalation of asbestos fibres
- asbestos used in building trade for fire proofing, pipe lagging, electrical wire insulation and roofing felt
- chrysotile (white asbestos) - least fibrogenic
- amosite (brown asbestos) - intermediate fibrogenicity, least common
- crocicolite (blue asbestos) - most fibrogenic
- presents with progressive dyspnea, clubbing and fine end inspiratory crackles
- causes pleural plaques
- increased risk of bronchial adenocarcinoma and mesothelioma
- mesothelioma can be diagnosed by thoracoscopy and biopsy

Pneumothorax

Pneumothorax is the presence of gas in pleural space

Primary spontaneous pneumothorax
- occurs without antecedent trauma to thorax and in the absence of underlyign lung disease, usually due to rupture of apical pleural blebs.
- occurs almost exclusively in smokers (lifetime risk of 12% in smoker as compared to 0.1% in non smoker)
- initial recommended treatment : simple aspiration
- supplementary high flow oxygen should be given to reduce the total pressure of gases in pleural capillaries by reducing the partial pressure of nitrogen, thus increase the pressure gradient between pleural capillaries and pleural cavity thereby increasing absorption of air from pleural cavity
- strong emphasis should be placed on the relationship between the recurrence of pneumothorax and smoking in an effort to encourage patient to stop smoking (recurrence rate of 54% within first 4 years)



Secondary pneumothorax
- due to chronic obstructive pulmonary disease
- clinical symptoms associated with secondary pneumothoraces are more severe than those associated with primary spontaneous pneumothoraces (lack of pulmonary reserve)



Traumatic pneumothorax
- penetrating or non-penetrating chest trauma
- should be treated with tube thoracostomy unless they are very small

Tension pneumothorax
- positive pleural pressure is life threatening because ventilation is severely compromised and positive pressure is transmitted to mediastinum, resulting in decreased venous return to the heart and reduced cardiac output
- large bore needle should be inserted into pleural space through the second anterior intercostal space

Size of pneumothorax depending on the visible rim between lung margin and chest wall
- small < 2cm (less than 50% of hemithorax)
- large ≥ 2cm (more than 50%)



Pneumothoraces which failed to respond within 48 hours should be referred to a respiratory physician. In case of persistent air leak or failure of lung to re-expand, the managing respiratory specialist should seek and early (3-5days) thoracic surgical opinion

Patients discharged without intervention should avoid air travel until a chest radiograph confirmed the resolution of pneumothorax. Diving should be permanently avoided after pneumothorax unless patient had bilateral surgical pleurectomy

Source: BTS guidelines for the management of spontaneous pneumothorax
             18th edition Harrison's principle of internal medicine

Aspergillosis

- caused by A.fumigatus (most common), A.flavus and A.niger
- these fungi are ubiquitous in environment and commonly found on decaying leaves and trees
- human infected by inhalation of spores
- 3 major forms

i) Allergic bronchopulmonary aspergillosis (ABPA)
- commoner among asthmatics with variable airflow obstruction
- Aspergillus grows in the wall of bronchi
- presents with wheeze, cough, fever and malaise, eventually produce proximal bronchiectasis
- type III hypersensitivity reaction
- suspect if asthma is refractory and is associated with fever, cough and grey/black sputum
- eosinophilia and IgE levels extremely high
- serum precipitins and skin prick test both positive
- abnormal chest X ray (transient pulmonary shadow)
- treatment: prednisolone 30mg daily and prolonged course of itraconazole (up to 4 months)

ii) Aspergilloma
- masses of fungal mycelia that grow in pre-existing lung cavities
- hemoptysis is common symptom
- CXR: round lesion with air halo above it
- high serum precipitins (continuing antigenic stimulation), negative skin prick test
- treatment: surgical resection, itraconazole (if unfit for resection), arterial embolisation if life threatening hemoptysis

iii) Invasive aspergillosis
- occurs in immunosuppressed
- presents with acute pneumonia, meningitis or intracerebral abscess, lytic bone lesions, granulomatous lesions in liver
- treatment: IV voriconazole or amphotericin B

Alpha-1 antitrypsin deficiency

- autosomal recessive
- defective gene in chromosome 14
- alpha-1 antitrypsin protein is synthesized by hepatic cells and released into circulation. In lungs, its primary function is to inactivate neutrophil elastase (enzyme released during phagocytosis in alveolus)
- encoded by protease inhibitor (Pi) locus
- most common (90%) allele is M (PiM). Normal is homozygous (PiMM)
- PiZZ have only 15-20% of normal blood alpha-1 antitrypsin level, which is severe
- Heterozygotes (PiMZ, PiMS, PiSZ) have less severe phenotypes
- smoking is the greatest risk factor for development of emphysema in adults with alpha-1 antitrypsin deficiency
- lung compliance increased in emphysema
- majority of patients with clinical liver disease are homozygotes with PiZZ phenotype, which can produce jaundice and liver problems in neonates within few days of birth

Byssinosis

- caused by cotton dust
- symptoms typically start on the first day back at work after a break (Monday sickness) with improvement as the week progresses
- presents with chest tightness, cough and breathlessness
- most likely aetiology is endotoxins from bacteria present in raw cotton causing constriction of airways of the lung
- CXR is normal

Coal worker pneumoconiosis

- related to total coal dust exposure
- simple CWP characterised by small rounded opacities (<1.5mm) on chest X-ray, and is associated with emphysema. Asymptomatic
- Progressive massive fibrosis (PMF)
    - development of larger opacities (>3mm)
    - lesion usually in upper zone
    - ANA and RF often positive
    - mixed restrictive and obstructive lung defect with reduced transfer factor
    - presents with melanoptysis
- Caplan syndrome = pneumoconiosis + rheumatoid arthritis
    - manifest as multiple round pulmonary nodules

Causes of lung fibrosis

Upper lobe fibrosis "BREAST X"

B: bronchopulmonary aspergillosis
R: radiotherapy
E: extrinsic allergic alveolitis
A: ankylosing spondylitis
S: sarcoidosis
T: tuberculosis
X: histiocytosis X

Lower lobe fibrosis "CRABSS"

C: cryptogenic fibrosing alveolitis
R: rheumatoid arthritis
A: asbestosis
B: bleomycin
S: SLE
S: scleroderma

Surgical resection of lung cancer - contraindication

Contraindications for surgical resection of lung cancer

- FEV1 less than 1.5L for lobectomy ; 2.0L for pneumectomy
- mediastinal lymph node more than 1cm
- staging more than IIIB
- recurrent laryngeal nerve involvement
- malignant pleural effusion present
- proven metastasis

rheumatoid pleural effusion

- occurs in 5% of RA
- majority resolved spontaneously in 3 months
- pleural fluid analysis
   - exudate
   - low pH (<7.2)
   - high LDH (>700)
   - low glucose level (<1.6)
   - large amount of cholesterol

Hypereosinophilic syndrome

- characterised by persistently elevated eosinophil count for at least 6 months with involvement of heart, CNS and bone marrow
- eosinophil count more than 1.5X10⁹/L
- presented with weight loss, rashes, fever, peripheral neuropathy, edema, cardiac disturbance
- exclude Strongyloides stercoralis (can cause hyperinfection syndrome if given steroid)
- 2 forms of heart involvement : endomyocardial fibrosis (Davies disease), Loeffler's endocarditis
- treatment: steroid and hydroxurea

acute respiratory distress syndrome

- diagnostic criteria
  i) acute onset
  ii)widespread bilateral CXR infiltrates
  iii)refractory hypoxemia (PaO2/FiO2< 200mmHg)
  iv)PCWP < 18mmHg

- causes
   direct: pneumonia, aspiration of gastric contents, inhalational injury, fat embolism
   indirect: sepsis, severe trauma with shock, pancreatitis, cardiopulmonary bypass
- first sign is often unexplained tachypnea, followed by increasing hypoxaemia with central cyanosis and breathlessness
- management is supportive and based on treatment of underlying cause.

extrinsic allergic alveolitis

- due to inhalation of a number of different antigens, most common being microbial spores containing vegetable matter.
- delayed hypersensitivity reaction which maybe immune complex (III) or cell mediated (IV)
- eg: farmer's lung (Micropolyspora faeni), bird fancier's lung, maltworker's lung, humidifier fever
- typically fever, malaise, cough and shortness of breath several hours after exposure to antigen.
- basal crackle is a feature
- NO wheeze
- causes upper zone fibrosis
- NO eosinophilia
- positive serum precipitating antibodies (circulating IgG precipitins)
- treatment: avoidance of causative allergen and long term corticosteroid therapy

carbon monoxide transfer factor

- transfer factor is a measure of transfer of gas across the alveolar capillary membrane and reflects the uptake of oxygen from alveoli into the red cells.Transfer coefficient is KCO.
- TLCO is the product of KCO and alveolar volume
- any factors which increases the number of red cells that come into contact with carbon monoxide will increase TLCO and KCO - alveolar hemorrhage, alveolar inflammation, asthma, exercise, polycythemia, left to right shunt (eg:ASD)
- causes of decreased TLCO and KCO - anemia, interstitial lung disease, multiple pulmonary emboli, lymphangitis, primary pulmonary hypertension, obstructive airway disease
- extrapulmonary restriction (thoracic cage deformities,pleural disease, respiratory muscle weakness) causes reduced TLCO but raised KCO (increase density of blood per unit lung volume)

Bronchiolitis obliterans organizing pneumonia (BOOP)

- a.k.a cryptogenic organizing pneumonia
- non specific inflammatory pulmonary process with buds of granulation tissue forming in distal air spaces.
- diagnosis is suspected after there is no response to multiple antibiotics and blood and sputum culture are negative for organisms
- presented with non specific symptoms of fever, dry cough, malaise, anorexia and weight loss.
- consolidation typically occurs in different places in different time
- treatment : steroid

Churg-Strauss syndrome

- eosinophilic granulomatous inflammation of respiratory tract with small and medium vessels necrotizing vasculitis
- pANCA is positive (50%)
- leukotriene inhibitor allow steroid doses to be lowered and this may unmask underlying vasculitis
- causing focal segmental glomerulonephritis
- principle cause of morbidity and mortality are myocarditis and myocardial infarction secondary to coronary arteritis
- serum IgE is commonly elevated and correlates with disease severity
- treatment: glucocorticoids, azathioprine, cyclophosphamide
- with treatment, 1 year survival is 90% and 5 year survival is 62%

mnemonic : BEAN SAP


BE: Blood Eosinophilia
A  : Asthma
N  : Neuropathy (mononeuritis multiplex) - usually common peroneal nerve
S  :  Sinus abnormality
A  : Allergies
P  : Perivascular eosinophils / vasculitis

Legionella pneumonia

- Outbreak seen in previously fit individuals staying in hotels/institution where shower facilities/cooling systems are contaminated with the organism
- Flu-like symptoms, fever, malaise and myalgia typically precede a dry cough and dyspnea
- associated with hyponatraemia, lymphopenia and diarrhea
- diagnosis is by urinary Legionella antigen test, and four-fold increase in antibody titres
- treatment: Macrolide (Clarithromycin), ciprofloxacin and rifampicin
- mortality is 15-30% especially in elderly

Goodpasture syndrome

- occurs in people age more than 16 (male:female = 6:1)
- type II cytotoxic reaction (antibodies against basement membrane of both kidney and lungs)
- 80% HLA BR2 positive
- triad of glomerulonephritis, pulmonary hemorrhage and anti-GBM positive (against alpha-3 chain of type IV collagen) *alpha-5 in Alport's syndrome
- starts with URTI symptoms followed by cough, hemoptysis, tiredness and anemia.
- acute glomerulonephritis may presents with asymptomatic proteinuria or microscopic hematuria
- chest X-ray: bilateral diffuse infiltrates in lower zone, transient blotchy shadows (intrapulmonary hemorrhage)
- diffusion capacity for carbon monoxide is increased (pulmonary hemorrhage)
- diagnosis: renal biopsy (gold standard) - crescentic nephritis
- serial TLCO measurement can be used to monitor progresssion
- ANCA may be positive
- treatment: corticosteroid, cyclophosphamide, plasmapheresis