Differentials

Common

Chronic obstructive pulmonary disease (COPD)

History

progressive dyspnoea over a period of years, slowly worsening exercise tolerance; chronic productive cough (may be unproductive), typically worse in the morning and after exercise; risk factors, for example, current or prior history of smoking, family history of COPD, childhood respiratory infections, occupational exposure to smoke, fumes, chemicals; may be comorbidities; exacerbations present with fever, subacute increase in dyspnoea, increased sputum production, change in sputum character; severe degree of impairment in young patient or patient with minimal or no smoking history suggests alpha-1 antitrypsin deficiency

Exam

facial plethora, cyanosis, laryngeal height of 4 cm or less, pursed lip breathing, hyper-expanded chest, prolonged exhalation, rhonchi, and wheeze; may be clubbing; severe cases: resting or exercise hypoxaemia; may be pulsus paradoxus, mental state changes

1st investigation
  • spirometry:

    decreased forced expiratory volume in the first second of expiration (FEV1), decreased FEV1/forced vital capacity (FVC) ratio

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Other investigations
  • pulmonary function tests:

    increased residual volume (RV), increased total lung capacity (TLC), decreased diffusing capacity of lung for carbon monoxide (DLCO)

    More
  • chest x-ray:

    increased lung volume, flattened hemidiaphragms may be present

    More
  • ABG:

    hypoxaemia, hypercapnia

    More

Congestive heart failure

History

orthopnoea, paroxysmal nocturnal dyspnoea, exertional dyspnoea, dyspnoea may be chronic with acute exacerbations, chest pain, ankle swelling; rapidly progressive failure; dyspnoea dominates the clinical picture

Exam

distended neck veins, fine bibasal rales, displaced apex beat, S3 gallop rhythm, peripheral oedema, may be increased abdominal girth, may be cyanosis and altered mental state

1st investigation
  • chest x-ray:

    cardiomegaly, bilateral lower lobe shadowing, pleural effusion, enlarged hilar vessels, upper lobe diversion, fluid in horizontal fissure, Kerley B-lines

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  • echocardiogram:

    valvular heart disease or regional/global wall motion abnormalities

  • B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP):

    elevated

    More
Other investigations
  • serum electrolytes:

    may be hyponatraemia

  • bedside lung ultrasonography:

    point of care ultrasound (POCUS) may demonstrate the presence of B-lines

    More
  • ECG:

    no specific pattern associated with heart failure exacerbation; Q wave, ST segment depressions, T wave inversion, left bundle branch block, and rhythm changes (atrial fibrillation and flutter) can all be seen

  • cardiac enzymes:

    may be elevated, as a reflection of myocardial strain and injury

    More

Asthma

History

episodic wheezing, cough, chest tightness and dyspnoea, symptom variability - may be seasonal, or following viral infection or exposure to aeroallergen, cool air, or exercise; possible history of other atopic diseases; onset of symptoms normally in childhood

Exam

may be normal in between exacerbations, prolonged expiratory phase, wheeze, and rhonchi; acute severe asthma attack may include: severe breathlessness (including too breathless to complete sentences in one breath), tachypnoea, tachycardia, silent chest, cyanosis, accessory muscle use, altered consciousness or collapse

1st investigation
  • spirometry (FEV1/FVC ratio):

    FEV1/FVC ratio: below the lower limit of normal (LLN; if available) or <70% (if LLN not available) is positive for airflow obstruction

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  • peak expiratory flow (PEF):

    may be reduced; may be variability (>10%) of measurements recorded at different times of the day

    More
Other investigations
  • bronchial provocation testing:

    airway hyper-responsiveness

    More
  • fractional exhaled nitric oxide test (FeNO):

    elevated FeNO (≥40 parts per billion) supports the diagnosis of asthma

  • FBC:

    normal or elevated eosinophils and/or neutrophilia

  • immunoassay for allergen-specific IgE:

    may be positive for allergen

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  • skin prick allergy testing:

    may be positive for allergen

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  • 6-week trial of inhaled corticosteroids:

    symptomatic and objective improvement in response

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Pneumonia (bacterial, viral, fungal, tuberculous)

History

sudden or sub-acute onset of fever, chills, cough, pleuritic chest pain, and dyspnoea; cough typically produces purulent sputum, but may be dry in some viral pneumonias and early bacterial pneumonia; onset is more insidious in fungal and tuberculous infections; night sweats, weight loss and malaise may occur in tuberculous infection

Exam

fever, tachycardia, tachypnoea, crackles, may be focal chest signs of consolidation: dullness on percussion, asymmetric chest expansion, bronchial breathing; may be signs of effusion: focal decreased breath sounds, and decreased vocal resonance and tactile fremitus; less frequently, jaundice; severe cases: hypoxaemia, cyanosis, altered mental state, and respiratory failure

1st investigation
  • chest x-ray:

    lobar infiltrate, cavitation, interstitial infiltrates

  • sputum Gram stain and culture:

    may demonstrate presence of bacteria

    More
Other investigations
  • FBC:

    elevated WBC with/without neutrophilia and left shift may be present

  • C-reactive protein:

    elevated

    More
  • LFTs:

    elevated serum transaminases may be present with atypical pneumonia

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  • procalcitonin:

    elevated in bacterial pneumonia

    More
  • ABG:

    hypoxaemia and respiratory alkalosis may be present in severe pneumonia

  • blood cultures:

    may be positive for specific organism

    More
  • serum urea or serum urea/serum albumin ratio:

    elevated levels of either test predict poor prognosis

    More
  • urinary antigen testing for Legionella and pneumococcus:

    positive for Legionella or pneumococcal antigens

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  • influenza molecular assay:

    positive in influenza

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  • respiratory virus PCR:

    may be positive for respiratory syncytial virus, human metapneumovirus, adenovirus, rhinovirus, or parainfluenxavirus.

Coronavirus disease 2019 (COVID-19)

History

dyspnoea may be accompanied by dry cough and fever; other common symptoms include anosmia, ageusia, fatigue, anorexia, myalgia, and sore throat; may be a travel history to an affected area or close contact with a suspected or confirmed case in the 14 days prior to symptom onset.

Exam

dyspnoea, may also have fever; patients with pneumonia or respiratory distress syndrome may have inspiratory crackles, rales, and/or bronchial breathing; patients with respiratory distress syndrome may have tachycardia, tachypnoea, or cyanosis accompanying hypoxia

1st investigation
  • real-time reverse transcription polymerase chain reaction (RT-PCR):

    positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA

    More
Other investigations
  • ABG:

    may show low partial oxygen pressure

    More
  • FBC:

    leukopenia; lymphopenia; leukocytosis

    More
  • coagulation screen:

    elevated D-dimer; prolonged prothrombin time

    More
  • comprehensive metabolic panel:

    elevated liver transaminases; decreased albumin; renal impairment

    More
  • serum procalcitonin:

    may be elevated

    More
  • serum C-reactive protein:

    may be elevated

    More
  • serum lactate dehydrogenase:

    may be elevated

    More
  • blood and sputum cultures:

    negative for bacterial infection

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  • chest x-ray:

    unilateral or bilateral infiltrates

  • chest CT:

    bilateral ground-glass opacity or consolidation

Croup

History

Sudden-onset ‘seal-like’ barking cough, voice hoarseness; typically affects children aged 6 months to 3 years; symptoms worse at night and when agitated

Exam

Stridor, respiratory distress, sternal and/or intercostal recession; asynchronous chest and abdominal wall movement, fatigue and hypoxia indicate impending respiratory failure

1st investigation
  • none:

    clinical diagnosis

Other investigations
  • x-ray anteroposterior and lateral neck:

    steeple sign in anteroposterior view or normal

    More

Acute coronary syndrome (ACS)

History

typically presents with central chest pain radiating to shoulders and neck; may cause dyspnoea alone in atypical presentations (especially in women and patients with diabetes); risk factors may be present: smoking, age >45 years (men) or >55 years (women), positive family history of premature coronary artery disease, hypertension, hyperlipidaemia, diabetes, stroke, or peripheral arterial disease

Exam

may be clammy and hypotensive; S3 or S4 gallop rhythm and pulmonary rales may be present

1st investigation
  • ECG:

    ST elevation (ST-elevation myocardial infarction [STEMI]), T-wave inversion and ST-segment depression (non-ST-elevation myocardial infarction [NSTEMI] and unstable angina); presence of Q waves indicates myocardial injury

    More
  • cardiac enzymes:

    elevated troponin I/T, elevated creatine kinase (CK) in STEMI and NSTEMI; not elevated in unstable angina

    More
  • chest x-ray:

    normal or signs of heart failure, such as increased alveolar markings

Other investigations
  • echocardiogram:

    wall motion abnormalities

    More
  • coronary angiography:

    STEMI: critical occlusion of a coronary artery; NSTEMI, unstable angina: may be evidence of coronary artery narrowing

Stable angina

History

chest pain from exertion lasting less than 20 minutes, pain not rapidly increasing, relieved by glyceryl trinitrate or rest; may not be associated with dyspnoea; risk factors may be present: smoking, age (men >45, women >55 years), positive family history of premature coronary artery disease, hypertension, hyperlipidaemia, diabetes, stroke, or peripheral arterial disease

Exam

exam may be normal or may have abnormal pulses if peripheral vascular disease present

1st investigation
  • ECG:

    may be normal/unchanged; may be non-specific ST changes and P-wave flattening; pathological Q waves or left bundle branch block may indicate previous infarction

  • cardiac enzymes:

    not elevated

Other investigations
  • chest x-ray:

    normal or cardiomegaly

  • stress test:

    ≥1 mm of horizontal or down-sloping ST-segment depression or ST-segment elevation during or after exercise considered positive for ischaemia; high-risk disease: regional wall motion abnormalities and left ventricular dysfunction

    More
  • coronary angiography:

    may be evidence of coronary artery narrowing

  • CT coronary angiography:

    identification of stenosis

    More

Arrhythmias

History

may be sudden-onset weakness, light-headedness, syncope, palpitations; possible history of coronary artery disease or previous arrhythmia

Exam

tachycardia or bradycardia; signs of inadequate cardiac output (pallor, diaphoresis, decreased mental status); peripheral oedema and pulmonary rales may be present

1st investigation
  • ECG:

    arrhythmia (e.g., atrial fibrillation, atrial flutter, complete heart block)

    More
Other investigations
  • Holter monitor:

    episodic arrhythmia

Interstitial lung disease

History

slowly progressive dyspnoea and a chronic, dry cough; may be risk factors including smoking, rheumatological diseases, exposure to solvents, organic dust, and moulds, chemotherapy and radiotherapy, and certain medications, although many cases are idiopathic

Exam

dry crackles; hypoxaemia, cyanosis, and clubbing may be present

1st investigation
  • chest x-ray:

    diffuse reticulonodular changes, decreased lung volume

  • CT chest:

    diffuse reticulonodular changes

    More
Other investigations
  • lung biopsy:

    interstitial pneumonitis

    More
  • pulmonary function tests:

    restrictive pattern; isolated reduction in DLCO may be the first sign.

Bronchiectasis

History

chronic cough, chronic daily purulent sputum production, and dyspnoea; possible history of prior pulmonary infections or viral pneumonias in childhood

Exam

prolonged expiratory phase, crackles, rhonchi, and wheeze; clubbing, cyanosis, and hypoxaemia may be present

1st investigation
  • high-resolution CT chest:

    thickened airways, irregular opacities (predominantly in lower zones), areas of atelectasis, bronchial dilation, tram-tracking, lack of airway size tapering

    More
  • chest x-ray:

    thickened airways, irregular opacities (predominantly in lower zones), areas of atelectasis

    More
  • pulmonary function tests:

    obstructive ventilatory deficit

Other investigations

    Non-infective pneumonitis (eosinophilic, radiation, aspiration, hypersensitivity pneumonitis)

    History

    fever, chills, cough (dry or productive), and dyspnoea; myalgias, pleuritic chest pain, and night sweats may be present; history of radiation to chest 1 to 6 months before presentation in radiation pneumonitis; episodes of clouded consciousness, choking, and aspiration in aspiration pneumonitis; exposure to organic antigens (e.g., bath tub, birds, hay) in hypersensitivity pneumonitis

    Exam

    crackles; wheeze and rhonchi less common; hypoxaemia and respiratory failure may be present in severe cases

    1st investigation
    • chest x-ray:

      alveolar infiltrates

      More
    • CT chest:

      patchy, nodular infiltrates

      More
    • antibody to causative antigen:

      positive

      More
    • bronchoalveolar lavage:

      lymphocytosis; eosinophilia in eosinophilic pneumonitis

      More
    Other investigations
    • pulmonary function test:

      Restrictive; mixed restrictive/obstructive

      More
    • bronchoscopic biopsy:

      granulomata in hypersensitivity pneumonitis

    Acute bronchitis

    History

    upper respiratory tract symptoms; cough; prolonged coughing and dyspnoea (especially on exposure to cold air, exercise, or irritants) may occur

    Exam

    fever, cough, inability to take deep breaths ('cough readiness'); lung examination may be normal or reveal rhonchi and wheeze

    1st investigation
    • none:

      clinical diagnosis

      More
    Other investigations
    • chest x-ray:

      may be helpful to exclude pneumonia, other causes of cough and fever

    Laryngitis

    History

    upper respiratory tract symptoms; hoarseness; dyspnoea; history of excessive vocal use, e.g., singers

    Exam

    may be hyperaemia of oropharynx; enlarged tonsils with or without exudate

    1st investigation
    • none:

      clinical diagnosis

      More
    Other investigations
    • laryngoscopy:

      oedema and erythema of the vocal folds

    Pulmonary embolism (thrombotic, air, amniotic fluid, tumour)

    History

    sudden-onset dyspnoea and chest pain; may be pre-syncope or syncope, haemoptysis, palpitations, may be asymptomatic; possible history of previous venothromboembolic disease, inadequate anticoagulation, immobilisation, admission to hospital, travel, vascular access, leg injury, malignancy, or childbirth

    Exam

    tachycardia, tachypnoea, may be hypotension, cyanosis, hypoxaemia, and neck vein engorgement, may present with lower extremity oedema

    1st investigation
    • D-dimer:

      elevated

      More
    • CT pulmonary angiography:

      presence of embolus

      More
    Other investigations
    • ventilation-perfusion (V/Q) scan:

      V/Q mismatch

      More
    • ABG:

      may show hypoxaemia and hypocapnia

    • chest x-ray:

      usually normal, but may show peripheral, triangular opacity (Hampton's hump), regional oligaemia (Westermark sign), or enlarged pulmonary artery (Fleischner sign); may also demonstrate a pleural effusion

      More
    • echocardiogram:

      right ventricular wall hypokinesis (McConnell's sign) may indicate a major embolus

    • ECG:

      may show atrial arrhythmias, tachycardia, new right axis deviation, new right bundle branch block, S wave in lead I, Q wave with T-wave inversion in lead III

    • serum brain natriuretic peptide (BNP):

      may be elevated or normal; insensitive/non-specific for diagnosis; useful for prognosis, may predict a major embolus

      More

    Pleural effusion

    History

    symptoms depend on rate of fluid accumulation and fluid volume; pleuritic chest pain and a dull ache may be present

    Exam

    asymmetrical chest expansion, 'stony' dullness to percussion, decreased tactile fremitus, decreased vocal resonance and absent breath sounds are typical in pleural effusion; examination may be normal in pleural tumours

    1st investigation
    • chest x-ray:

      blunting of costophrenic angle and opacification of lower lung field in pleural effusion; pleural thickening in pleural tumours

      More
    Other investigations
    • bedside ultrasonography:

      may demonstrate the presence of hypoechogenic fluid or hyperechogenic pleural tumour

    Pleuritis

    History

    unilateral chest pain significantly exacerbated by deep breathing

    Exam

    splinting of the chest (i.e., preferential movement of unaffected side) may be present; dullness to percussion and decreased breath sounds may be present on the affected side in the presence of a pleural effusion

    1st investigation
    • none:

      clinical diagnosis

      More
    • chest x-ray:

      blunting of costophrenic angle and decreased lung volume in pleural effusion, reduced size of intercostal spaces

      More
    Other investigations

      Anaemia

      History

      symptoms depend on severity and acuity of anaemia; presentation ranges from insidious onset of exertional dyspnoea to severe dyspnoea at rest; associated symptoms related to impaired oxygen delivery to tissues (confusion, lethargy, syncope, coma) and compensatory mechanisms (palpitations, bounding pulses) occur

      Exam

      characterised by nail-bed and conjunctival pallor; jaundice and hepatosplenomegaly may be present in haemolytic anaemia

      1st investigation
      • FBC:

        low haemoglobin

        More
      • ferritin:

        decreased or normal

        More
      Other investigations

        Gastro-oesophageal reflux disease (GERD)

        History

        presents with heartburn, overt regurgitation of gastric contents into the throat, and dysphagia; nausea, odynophagia, and chest pain may be present; symptoms are typically post-prandial, occur in supine position, and may be associated with certain foods

        Exam

        typically normal

        1st investigation
        • trial of proton pump inhibitor:

          Symptom improvement

          More
        • oesophagoscopy:

          oesophagitis, erosions, mucosal metaplasia

          More
        Other investigations
        • 24-hour pH monitoring:

          periods of low oesophageal pH

          More

        Ascites

        History

        insidious-onset weight gain and increased abdominal girth; possible history of liver disease (e.g., viral hepatitis, liver cirrhosis) or alcohol misuse

        Exam

        stigmata of chronic liver disease (e.g., spider naevi, palmar erythema) and jaundice are usually present; abdominal examination reveals abdominal distension and distended abdominal wall superficial veins

        1st investigation
        • none:

          clinical diagnosis

          More
        Other investigations
        • abdominal ultrasound:

          ascitic fluid

          More
        • chest x-ray:

          pleural effusion, elevated hemidiaphragms, small lung volume

          More

        Shock

        History

        possible history of infection/sepsis, anaphylaxis, cardiac pump failure, toxin exposure, or hypovolaemia leading to inadequate tissue perfusion and end-organ dysfunction; may be a history of urinary, respiratory, or intra-abdominal sepsis, exposure to medications and insect bites, cardiac chest pain, or haemorrhage (e.g., haematemesis, melaena)

        Exam

        hypotension, tachycardia, tachypnoea, and decreased oxygen saturation are common; brain underperfusion causes varying degrees of decreased mental status; pallor or hyperaemia may accompany shock; distributive shock results in warm and flushed extremities; cardiogenic shock leads to cold and clammy extremities; diffuse rash may accompany bacterial toxin production; rhonchi, wheeze, and crackles may be present; abdominal tenderness may reflect an intra-abdominal infectious process or gut ischaemia

        1st investigation
        • FBC:

          elevated or decreased WBC, low haemoglobin

          More
        • serum urea nitrogen:

          elevated

          More
        • serum creatinine:

          elevated

          More
        • serum bicarbonate:

          decreased

          More
        • serum lactate:

          elevated

          More
        • ECG:

          tachycardia, may be ST-segment and T-wave changes

          More
        • chest x-ray:

          may be unilateral infiltrate, signs of pulmonary oedema

          More
        • blood cultures:

          may be positive

          More
        Other investigations
        • serum troponin:

          may be elevated

          More
        • echocardiogram:

          may have segmental wall motion abnormalities, global myocardial dysfunction, hyperdynamic myocardium

          More

        Pulmonary tumours

        History

        cough; haemoptysis (usually low volume) may be present in proximal airway tumours; chest pain; hoarseness; confusion, focal neurological defects, and bone pain may reflect extrathoracic spread; asymptomatic disease may be incidentally detected by presence of a lung nodule on chest x-ray

        Exam

        may be normal; may be unilateral wheeze and decreased breath sounds in large airway lesions; crackles and rhonchi may be present in post-obstructive pneumonia; dullness to percussion and decreased fremitus may indicate malignant pleural effusion

        1st investigation
        • chest x-ray:

          lung nodule or mass

          More
        • CT chest:

          lung nodule, lymphadenopathy

          More
        Other investigations
        • biopsy (bronchoscopic or transthoracic):

          lung cancer

          More

        Anxiety and panic attacks

        History

        most commonly young to middle-aged women, but may affect both sexes at any age; possible prior history of anxiety, phobias, and panic; dyspnoea may be accompanied by a choking sensation, discomfort in various locations, dizziness, and a sense of fear

        Exam

        tachycardia, tachypnoea, and sweating may be present; patient may hyperventilate and sigh frequently; Chvostek's and Trousseau's signs may be present

        1st investigation
        • no initial test:

          usually a clinical diagnosis; although, if diagnosis is in doubt, tests may be done to rule out other conditions

        Other investigations
        • ABG:

          respiratory alkalosis

          More

        Normal ageing, deconditioning, and obesity

        History

        dyspnoea typically of insidious onset and exertional, and may be associated with undertaking an unusual degree of physical exercise

        Exam

        typically normal

        1st investigation
        • none:

          clinical diagnosis

          More
        Other investigations
        • exercise testing:

          low exercise capacity

        Uncommon

        Sepsis

        History

        symptoms of localised infection, non-specific symptoms include fever or shivering, dizziness, nausea and vomiting, muscle pain, feeling confused or disoriented; may be history of risk factors e.g., immunosuppression, pregnancy or postpartum period, frailty, recent surgery or invasive procedures, intravenous drug use or breach of skin integrity

        Exam

        tachycardia, tachypnoea, hypotension, fever (>38ºC) or hypothermia (<36ºC), prolonged capillary refill, mottled or ashen skin, cyanosis, low oxygen saturation, newly altered mental state, reduced urine output

        1st investigation
        • blood culture:

          may be positive for organism

          More
        • serum lactate:

          may be elevated; levels >2 mmol/L (>18 mg/dL) associated with adverse prognosis; even worse prognosis with levels ≥4 mmol/L (≥36 mg/dL)

          More
        • FBC with differential:

          WBC count >12 x 10⁹/L (>12,000/microlitre) (leukocytosis); WBC count <4 x 10⁹/L (<4000/microlitre) (leukopenia); or a normal WBC count with >10% immature forms; low platelets

          More
        • C-reactive protein:

          elevated

        • blood urea and serum electrolytes:

          serum electrolytes may be deranged; blood urea may be elevated

        • serum creatinine:

          may be elevated

          More
        • liver function tests:

          may show elevated bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase

          More
        • coagulation studies:

          may be abnormal

        • ABG:

          may be hypoxia, hypercapnia, elevated anion gap, metabolic acidosis

        Other investigations
        • ECG:

          may show evidence of ischaemia, atrial fibrillation, or other arrhythmia; may be normal

          More
        • chest x-ray:

          may show consolidation; demonstrates position of central venous catheter and tracheal tube

        • urine microscopy and culture:

          may be positive for nitrites, protein or blood; elevated leukocyte count; positive culture for organism

        • lumbar puncture:

          may be elevated WBC count, presence of organism on microscopy and positive culture

          More
        • sputum cultures:

          may be positive for organism

        Aortic dissection

        History

        typically presents with sudden, severe chest pain that may radiate to the back

        Exam

        may be normal, may be pallor, tachycardia, tachypnoea, hypotension with increased pulse pressure, and diminished peripheral pulses (especially lower extremities); diastolic precordial murmur suggesting aortic regurgitation may be heard over the precordium

        1st investigation
        • echocardiogram:

          increased size of ascending aorta, double lumen, dissection flap

          More
        • CT chest:

          aortic dissection, enlarged aorta, false lumen

          More
        Other investigations

          Sarcoidosis

          History

          frequently diagnosed in asymptomatic stage based on chest x-ray abnormalities; cough, dyspnoea, and chest pain are common; fever, myalgias, subcutaneous nodules, and erythema nodosum may be present

          Exam

          may be normal; may be wheeze and dry crackles

          1st investigation
          • chest x-ray:

            hilar adenopathy, reticulonodular changes, pulmonary fibrosis

            More
          • serum ACE:

            elevated

            More
          Other investigations
          • lung biopsy:

            non-caseating granulomata

            More

          Pulmonary contusion

          History

          history of blunt or penetrating trauma

          Exam

          signs of pulmonary oedema

          1st investigation
          • chest x-ray:

            infiltrates, which may be patchy or confluent; pulmonary oedema

          Other investigations
          • CT of the chest:

            infiltrates, pulmonary oedema

          • bedside ultrasonography:

            may be B-lines and C-lines

            More

          Epiglottitis

          History

          commonly in young children (aged 3-5 years), but may occur at any age; rapidly progressive sore throat, fever, odynophagia, dysphonia, drooling, hoarseness and stridor

          Exam

          child typically adopts the 'tripod' position (postures neck and head anteriorly and places hands on his/her knees); anterior oral examination may be normal; tenderness over anterior and lateral neck and hyoid bone, swelling on laryngoscopy; note: direct airway examination may precipitate airway obstruction

          1st investigation
          • none:

            clinical diagnosis

            More
          Other investigations
          • lateral neck x-ray:

            enlarged epiglottis - the 'thumb sign'[Figure caption and citation for the preceding image starts]: Lateral neck film demonstrating thumbprint sign (arrows)From the collection of Dr Petri [Citation ends].com.bmj.content.model.assessment.Caption@4437aa94

          • laryngoscopy:

            swollen epiglottis, aryepiglottic folds, and arytenoid cartilages

          Anaphylaxis

          History

          history of exposure of predisposed host to a medication, food product, or insect sting or bite; sudden dyspnoea and wheezing, choking sensation, voice changes, tongue swelling, rash, and itching; nausea, vomiting, and diarrhoea may be present

          Exam

          prolonged expiratory phase, wheeze, tachycardia, hypotension, facial and tongue oedema, cutaneous manifestations (urticaria, angio-oedema)

          1st investigation
          • none:

            clinical diagnosis

          Other investigations
          • serum tryptase:

            usually elevated

            More

          Angio-oedema

          History

          rapid development of skin or mucosal surface swelling; lips, mouth, larynx, and bowel most commonly involved; possible history of atopic diseases or ACE inhibitor use; dyspnoea may be present if larynx is involved

          Exam

          asymmetrical, prominent swelling of the involved part; urticaria may be present; respiratory compromise may be present if larynx is involved

          1st investigation
          • none:

            clinical diagnosis

          Other investigations
          • complement studies:

            C4 reduced in acquired angio-oedema; C1-esterase inhibitor reduced in hereditary angio-oedema; C1q normal in hereditary angio-oedema and reduced in acquired angio-oedema

            More

          Foreign body aspiration

          History

          possible history of epilepsy, syncope, altered mental status (e.g., intoxication, hypoglycaemia), or choking and coughing after ingestion of food (particularly nuts); history of choking not always present; may have had recurrent pneumonia

          Exam

          cyanosis, stridor, unilateral wheeze

          1st investigation
          • chest x-ray:

            unilateral atelectasis or hyperlucency

            More
          • CT chest:

            foreign body in airways

          Other investigations
          • bronchoscopy:

            presence of foreign body

            More

          Tracheobronchial tumours (benign or malignant)

          History

          dyspnoea may be constant or positional; cough (usually dry) and haemoptysis may be present; airway obstruction may lead to pneumonia, which markedly exacerbates symptoms

          Exam

          may be wheeze and stridor; hypoxaemia is a late finding

          1st investigation
          • chest x-ray:

            tracheal narrowing

            More
          • CT chest:

            tracheal narrowing

            More
          Other investigations
          • bronchoscopy:

            tracheal tumour

            More

          Retrosternal goitre

          History

          dyspnoea and wheezing are common; cough may be present; symptoms may be positional; chest pain, hoarseness, and Horner syndrome are less common; enlargement of ectopic thyroid tissue is accompanied by enlargement of orthotopic thyroid; may be history of orthotopic thyroid removal

          Exam

          goitre typically present; may be stridor, dyspnoea, and wheeze (especially with forced respiration); Pemberton manoeuvre (passive elevation of arms above head for 1 minute) may reveal symptoms by forcing thyroid tissue into the thoracic inlet

          1st investigation
          • chest x-ray:

            tracheal narrowing and deviation, upper mediastinal mass

            More
          • CT chest:

            retrosternal goitre with tracheal narrowing

            More
          Other investigations
          • spirometry:

            flattened inspiratory and expiratory portions of flow-volume loop

          Vocal cord dysfunction

          History

          exertional dyspnoea that may be associated with wheezing and stridor; symptoms may appear only in certain positions and are typically associated with a degree of anxiety

          Exam

          examination may be normal; forced exhalation or series of deep breaths may induce wheezing/stridorous sound

          1st investigation
          • laryngoscopy:

            paradoxical adduction of vocal cords on inspiration

            More
          • spirometry:

            flattening of inspiratory portion of flow-volume loop

            More
          Other investigations

            Pulmonary hypertension

            History

            insidious onset resulting in limitation of exercise capacity; exertional chest pain, exertional syncope, and symptoms of right-sided heart failure may develop

            Exam

            increased intensity of pulmonary component of S2 may be the only sign; distended neck veins, hepatomegaly, and peripheral oedema may be present in severe cases

            1st investigation
            • echocardiogram:

              elevated estimated pulmonary artery pressure, right ventricular strain

            Other investigations
            • right heart catheterisation:

              elevated pulmonary artery pressure

              More

            Hepatopulmonary syndrome

            History

            typical presentation includes dyspnoea; platypnoea (dyspnoea that is relieved on lying down) may be present; history of chronic liver disease

            Exam

            hypoxaemia with platypnoea-orthodeoxia (i.e., dyspnoea and hypoxia in upright position that improves in recumbent position) is typical; stigmata of chronic liver disease (e.g., spider naevi), jaundice, and ascites may be present

            1st investigation
            • ABG:

              hypoxaemia

            • contrast echocardiography:

              extracardiac shunt

              More
            Other investigations

              Pulmonary arteriovenous malformations

              History

              most commonly a manifestation of autosomal dominant hereditary haemorrhagic telangiectasia (HHT), but may be isolated; epistaxis, haemoptysis, dyspnoea, and gastrointestinal bleeding; large malformations associated with platypnoea (dyspnoea that is relieved on lying down)

              Exam

              small, red, elevated vascular malformations of the skin and mucous membranes are typical of HHT; hypoxaemia may be present; examination may be normal in isolated, non-HHT-related malformations

              1st investigation
              • chest x-ray:

                peripheral lung nodule

                More
              • CT chest:

                peripheral lung nodule

                More
              • contrast echocardiography:

                extracardiac shunt

                More
              • shunt fraction measurement:

                increased

                More
              Other investigations
              • technetium-macroaggregated albumin scintigraphy:

                may show extracardiac shunting with abnormal peripheral accumulation of aggregates

              Pulmonary veno-occlusive disease

              History

              slowly progressive dyspnoea that may be accompanied by chronic cough, chest pain, abdominal pain, or syncope

              Exam

              cyanosis, clubbing, loud P2, right ventricular heave, liver congestion, peripheral oedema

              1st investigation
              • chest x-ray:

                prominent pulmonary arteries, Kerley B-lines, pleural effusions

              Other investigations
              • CT chest:

                demonstrates mosaic ground glass opacities, centrilobular infiltrates, and pleural effusions; right heart catheterisation shows elevated pulmonary artery pressures but normal capillary wedge pressure

              Mesothelioma

              History

              asbestos exposure, often employment-related, with a latency period of 20 to 40 years; shortness of breath, dry non-productive cough, chest pain; non-specific symptoms (such as fatigue, fever, sweats, and weight loss) also common

              Exam

              decreased breath sounds and dullness to percussion on the affected side as a result of pleural effusion or bronchial obstruction on the affected side

              1st investigation
              • chest x-ray:

                unilateral pleural effusion, pleural thickening, reduced lung volume

                More
              • CT chest:

                pleural thickening, discrete pleural plaques, pleural or pericardial effusions; enlarged hilar or mediastinal lymph nodes; chest wall invasion

                More
              Other investigations

                Pneumothorax and pneumomediastinum

                History

                sudden-onset dyspnoea and unilateral chest pain; patient may be tall and asthenic; possible history of crack cocaine use, HIV, or lymphangioleiomyomatosis

                Exam

                unilaterally absent breath sounds and tympany on percussion of ipsilateral chest in pneumothorax; tracheal shift away from side of lesion in tension pneumothorax; subcutaneous emphysema in pneumomediastinum

                1st investigation
                • bedside lung ultrasonography:

                  POCUS may demonstrate pneumothorax; absence of pleural sliding, B-lines, and lung pulse

                  More
                • chest x-ray:

                  collapsed lung (total or partial) and unilateral lucidity ± mediastinal shift away from side of lesion in tension pneumothorax

                  More
                Other investigations

                  Haemothorax

                  History

                  history of blunt or penetrating trauma to the chest

                  Exam

                  signs of volume depletion, circulatory collapse, and shock

                  1st investigation
                  • chest x-ray:

                    fluid in the pleural space with blunting costophrenic angle

                    More
                  Other investigations
                  • bedside ultrasonography:

                    POCUS may identify hyperechogenic fluid within the pleural space, suggestive of haemothorax

                  Acquired valvular heart disease

                  History

                  dyspnoea on exertion, episodic chest pain, symptoms of congestive heart failure (weight gain, orthopnoea, paroxysmal nocturnal dyspnoea, ankle swelling); possible history of rheumatic fever; acute valvular dysfunction may follow a coronary event

                  Exam

                  murmur reflecting turbulence due to flow through a narrowed valve or regurgitation of blood; jugular venous distension, heart rhythm disturbances (especially atrial fibrillation), peripheral oedema, and hepatomegaly may be present

                  1st investigation
                  • echocardiogram with Doppler:

                    valvular insufficiency or stenosis

                    More
                  Other investigations
                  • chest x-ray:

                    enlarged heart chambers

                    More

                  Congenital heart disease

                  History

                  may be detected in newborn period, although may present at a later age; impaired exercise tolerance; chest pain, hypertension, and exertional syncope may be present; infrequently may present with consequences of intracardiac shunt (e.g., brain abscesses)

                  Exam

                  patent ductus arteriosus is characterised by wide pulse pressure, palpable, dynamic left apical impulse with a continuous machinery-like murmur; aortic coarctation is characterised by absent lower extremity pulses with hypertension in the upper extremities; tetralogy of Fallot is characterised by systolic murmur, absent P2, and cyanosis; cyanosis may be present in Eisenmenger's syndrome

                  1st investigation
                  • echocardiogram with Doppler:

                    abnormality specific to underlying defect

                    More
                  Other investigations
                  • chest x-ray:

                    enlargement of heart chambers, pulmonary vascular congestion

                    More

                  Cardiac drugs

                  History

                  presyncope, syncope; poor exercise tolerance; history of treatment with digoxin, calcium channel blockers, or beta-blockers

                  Exam

                  resting bradycardia

                  1st investigation
                  • ECG:

                    bradycardia

                    More
                  Other investigations
                  • exercise testing:

                    poor exercise tolerance, relative bradycardia

                    More

                  Myocardial disease (cardiomyopathy, myocarditis)

                  History

                  fatigue and decreased exercise tolerance; symptoms of heart failure (ankle swelling, increased abdominal girth, orthopnoea, paroxysmal nocturnal dyspnoea, chest pain) may be present; myocarditis frequently follows a viral infection; cardiomyopathy may be incidentally detected on chest x-ray

                  Exam

                  tachycardia, S3 or S4 gallop rhythm, systolic murmur of mitral or tricuspid regurgitation, neck vein distension, peripheral oedema, ascites, and hepatomegaly may be present

                  1st investigation
                  • ECG:

                    non-specific ST changes, ventricular extra beats; ST elevation in myocarditis

                  • echocardiogram:

                    ventricular dysfunction, segmental/global wall motion abnormalities

                    More
                  • serum troponin:

                    elevated in myocarditis

                    More
                  • chest x-ray:

                    cardiomegaly

                  Other investigations

                    Pericardial disease

                    History

                    chest pain; dyspnoea is typically ameliorated by assuming a sitting position and bending forwards; ankle swelling and increased abdominal girth may be the presenting symptoms; patients with constrictive pericarditis may have a history of chest surgery or chest radiation

                    Exam

                    tachycardia, distended neck veins, pulsus paradoxus (>10 mmHg decrease in systolic blood pressure with inspiration), peripheral oedema, ascites, pulsatile hepatomegaly, and pleural effusion may be present; pericardial friction rub is best heard over the left sternal border with the patient leaning forwards at end-expiration; distant heart sounds

                    1st investigation
                    • ECG:

                      electrical alternans, low QRS voltage

                      More
                    • echocardiogram:

                      pericardial effusion, tamponade

                      More
                    Other investigations
                    • chest x-ray:

                      enlarged cardiac silhouette in pericardial effusion/cyst/tamponade; small heart in constrictive pericarditis

                    Superior vena cava syndrome

                    History

                    insidious-onset dyspnoea, facial oedema, and head fullness

                    Exam

                    facial plethora, distension of neck and head veins[Figure caption and citation for the preceding image starts]: Prominent collateral vein on the anterior chest and abdominal wall in a patient with superior vena cava syndrome.From the collection of E Kempny. Reproduced under the Creative Commons CC BY-SA 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/) [Citation ends].com.bmj.content.model.assessment.Caption@6af729c2

                    1st investigation
                    • chest x-ray:

                      paramediastinal mass

                      More
                    Other investigations
                    • CT angiogram:

                      superior vena cava narrowing

                      More

                    Methaemoglobinaemia and carbon monoxide poisoning

                    History

                    methaemoglobinaemia presents with easy fatigability and headaches; symptoms may progress to obtundation, respiratory depression, and death in severe cases; symptoms may appear after exposure to specific drugs, either by ingestion (dapsone) or mucosal exposure (lidocaine, benzocaine); carbon monoxide poisoning may mimic a viral syndrome (headache, malaise, dizziness, nausea)

                    Exam

                    cyanosis, dyspnoea, and neurological changes may be present in methaemoglobinaemia; arrhythmias and mental status changes ranging from mild confusion to seizures and coma are common in carbon monoxide poisoning; cherry-red appearance of skin may be noted in carbon monoxide poisoning

                    1st investigation
                    • CO-oximetry:

                      elevated signal from methaemoglobin or carboxyhaemoglobin

                      More
                    • serum carboxyhaemoglobin:

                      in carbon monoxide poisoning: elevated to >3% in non-smokers and >15% in smokers

                      More
                    • serum lactate:

                      elevated

                      More
                    • serum troponin:

                      elevated

                      More
                    • ECG:

                      tachycardia, ST-segment and T-wave changes

                      More
                    Other investigations

                      Tetanus

                      History

                      history of exposure to Clostridium tetani spores through injury, foreign body retention, or in neonatal period; presentation ranges from localised muscle spasms of a limb to tonic, painful skeletal muscle contractions in severe cases; prodrome of restlessness, sweating, and tachycardia may be present; tetanic spasms may affect any muscle group and be triggered by non-specific stimuli (e.g., light, noise)

                      Exam

                      contraction of facial muscles results in lockjaw (trismus) or a sardonic smile (risus sardonicus); contraction of back muscles leads to opisthotonus; abdominal muscle contraction raises suspicion of a surgical abdomen

                      1st investigation
                      • none:

                        clinical diagnosis

                      Other investigations
                      • serum tetanus toxin:

                        positive

                        More
                      • clostridium tetani detection from wound or tissue swab:

                        presence of Clostridium tetani

                        More

                      Botulism

                      History

                      acute onset of bilateral bulbar neuropathy with symmetrical descending weakness; possible history of ingestion of contaminated, non-pasteurised food (food-borne botulism) 12 hours to 7 days before symptom onset, or wound contamination with Clostridium botulinum; nausea, vomiting, abdominal cramps, and diarrhoea may accompany blurred vision, diplopia, and facial paralysis

                      Exam

                      any cranial nerve may be involved, resulting in blurred vision, ophthalmoplegia, diplopia, dysarthria, nystagmus, ptosis, and facial weakness

                      1st investigation
                      • none:

                        clinical diagnosis

                        More
                      Other investigations
                      • serum C botulinum toxin:

                        positive

                        More
                      • stool C botulinum toxin:

                        positive

                        More

                      Phrenic nerve paralysis

                      History

                      recent surgical procedure, involving neck or chest, recent chest or neck trauma; in idiopathic cases, no such history can be elicited

                      Exam

                      dullness to percussion at lung base, no respiratory variability of the lower lung border

                      1st investigation
                      • chest x-ray:

                        elevated, relaxed hemidiaphragm

                      Other investigations
                      • dynamic chest fluoroscopy ('sniff test'):

                        paradoxical (upward) movement of the affected diaphragm

                      Amyotrophic lateral sclerosis

                      History

                      asymmetrical weakness of the distal muscles, inability to perform fine motor hand movements, or foot drop; possible difficulty in initiating movements and maintaining erect posture; personality changes may be noted by family members

                      Exam

                      signs attributable to upper and lower motor neuron disease (weakness, hyper-reflexia, spasticity, muscle atrophy, fasciculations) and bulbar involvement (dysphagia, dysarthria) may be present; drooling and sialorrhoea may be present; patients may display inappropriate affect with laughing, crying, and impaired judgement

                      1st investigation
                      • none:

                        clinical diagnosis

                        More
                      Other investigations
                      • electromyography:

                        acute and chronic denervation, fasciculation potentials

                      • nerve conduction studies:

                        normal

                        More

                      Polio and other acute viral anterior horn infections

                      History

                      polio presents with asymmetrical weakness (typically affects lower more than upper extremities and proximal more than distal muscles) and diminished deep tendon reflexes; neurological symptoms may be preceded by a viral prodrome of fever, nausea, malaise, and sore throat; muscle weakness quickly progresses and may lead to quadriplegia and respiratory failure; other infections of anterior horn cells (e.g., enteroviruses, West Nile virus) produce similar symptoms

                      Exam

                      asymmetrical muscle paresis or paralysis; sensory examination is typically normal; deep tendon reflexes are diminished

                      1st investigation
                      • lumbar puncture:

                        pleocytosis with lymphocyte predominance, elevated protein

                        More
                      • viral culture of throat secretions or faeces:

                        positive

                        More
                      Other investigations

                        Guillain-Barre syndrome

                        History

                        progressive symmetrical paralysis; muscle weakness typically starts in thigh muscles, but may involve any muscle group (e.g., arms, bulbar, ocular); patients may experience sensory phenomena (especially paraesthesias in hands and feet); urinary retention and ileus may be present

                        Exam

                        symmetrical muscle weakness is a hallmark sign; dysautonomia (tachycardia or bradycardia, labile blood pressure, orthostatic hypotension) may be present; deep tendon reflexes are characteristically absent or diminished

                        1st investigation
                        • lumbar puncture:

                          elevated protein level, normal pleocytosis

                        • nerve conduction studies:

                          conduction velocity slowing, patchy demyelination

                          More
                        Other investigations

                          Myasthenia gravis

                          History

                          muscular weakness of ocular or bulbar muscles; ptosis, diplopia, dysarthria, and dysphagia are common; muscle fatigability involving facial or limb muscles is less common

                          Exam

                          examination is variable; weakness of extra-ocular muscles (not restricted to specific cranial nerve), lack of facial expression, or peripheral muscle weakness and fatigability (typically affects arms more than legs) may be present; speech may be weak or indistinct

                          1st investigation
                          • serum antibodies to acetylcholine receptor:

                            positive

                            More
                          • electromyography:

                            decremental response on repetitive nerve stimulation

                            More
                          Other investigations
                          • serum antibodies to tyrosine kinase receptor:

                            positive

                            More

                          Respiratory muscle deficiency

                          History

                          onset of dyspnoea may be insidious (idiopathic diaphragmatic paralysis), or related to a known insult (e.g., trauma, surgery); dyspnoea typically worse in supine than upright position (orthopnoea) in diaphragmatic paralysis

                          Exam

                          detecting paradoxical diaphragm movement may be difficult; abdominal wall muscle weakness is easily detected by paradoxical, inward movement of abdominal wall during inspiration; weakness of non-respiratory muscles may be evident in paraparesis

                          1st investigation
                          • chest x-ray:

                            unilateral elevation of diaphragm, atelectasis

                            More
                          • dynamic fluoroscopy of the chest (sniff test):

                            unilateral paradoxical movement of diaphragm

                            More
                          • pulmonary function tests:

                            decreased forced vital capacity (FVC), >10% difference between supine and upright FVC

                            More
                          Other investigations

                            Paraneoplastic myasthenic syndrome

                            History

                            weakness in pelvic girdle and ascending pattern of motor disease progression; difficulty in getting up from a chair, easy fatigability, and muscle cramps; weakness improves transiently after brief exercise (post-exercise facilitation); autonomic dysfunction (erectile dysfunction, mouth dryness) may be present; weakness of upper girdle muscles and involvement of ocular and bulbar muscles is less common

                            Exam

                            predominantly lower-extremity weakness with absent reflexes; proximal muscles most commonly affected; symmetrical distribution of muscle involvement; no oculobulbar involvement

                            1st investigation
                            • antibodies to voltage-gated calcium channel:

                              positive

                              More
                            • electrophysiology testing:

                              characteristic pattern of pre-synaptic neuromuscular junction disorder

                            Other investigations

                              Thyroid disease

                              History

                              thyrotoxicosis presents with dyspnoea, decreased exercise tolerance, sweating, heat intolerance, fatigue, diarrhoea, urinary frequency, and weight loss; hypothyroidism and associated slowing of metabolism manifests with cold intolerance, constipation, and weight gain; women with hypothyroidism may experience oligomenorrhoea or amenorrhoea; snoring may appear or worsen with the development of hypothyroidism

                              Exam

                              signs of thyrotoxicosis include tachycardia (e.g., atrial fibrillation), tachypnoea, widened pulse pressure, warm and sweaty skin, exophthalmos, lid lag, and neck goitre; anxiety, restlessness, and agitation may also be present; signs of hypothyroidism include dry skin, generalised oedema, hypertension, and mental slowing

                              1st investigation
                              • serum thyroid-stimulating hormone (TSH):

                                elevated in hypothyroidism, decreased in hyperthyroidism

                                More
                              Other investigations
                              • serum free T3 and free T4:

                                elevated in hyperthyroidism, decreased in hypothyroidism

                              Cushing syndrome

                              History

                              progressive weight gain and exertional dyspnoea; careful history localises decreased exercise tolerance to muscle weakness; women may present with oligomenorrhoea or amenorrhoea

                              Exam

                              obesity with central distribution, moon facies, supraclavicular and nuchal fat pads; skin is thin and easily bruised; striae may be evident over the trunk and extremities; female patients may display hirsutism; hypertension may be present

                              1st investigation
                              • urinary cortisol:

                                elevated

                                More
                              Other investigations
                              • low-dose dexamethasone suppression test:

                                lack of cortisol production suppression

                                More

                              Phaeochromocytoma

                              History

                              episodic sweating, headache, and tachycardia; possible associated episodic dyspnoea and feelings of panic

                              Exam

                              examination between paroxysms of catecholamine release may be normal; some patients have sustained hypertension

                              1st investigation
                              • 24-hour urinary metanephrine and catecholamine collection:

                                elevated

                                More
                              Other investigations

                                Kyphoscoliosis and pectus excavatum

                                History

                                pectus excavatum develops in early childhood and may cause exertional dyspnoea; kyphoscoliosis develops in childhood or adolescence and is most commonly idiopathic or may be caused by neuromuscular disease, vertebral body destruction, or connective tissue disorders

                                Exam

                                pectus excavatum is characterised by lower sternum concavity and mild restriction to chest expansion, and has associated scoliosis in up to 15% of cases; kyphoscoliosis is characterised by anterior and lateral spinal deformation; degree of scoliosis and kyphosis may be under-appreciated due to compensatory changes in other bony structures

                                1st investigation
                                • spinal x-ray:

                                  abnormal curvature of spine or sternum

                                  More
                                Other investigations

                                  Diphtheria

                                  History

                                  upper respiratory tract symptoms; dysphagia, dysphonia, dyspnoea, and a croupy cough can develop; immunisation and travel history are important

                                  Exam

                                  typical brown-grayish pseudomembrane may be seen on the tonsils and/or pharynx

                                  1st investigation
                                  • bacteriological culture and microscopy:

                                    black colonies with halos on Tindale media, metachromatic granules on Loeffler media, irregular staining pleomorphic bacilli on microscopy

                                  Other investigations

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