Differentials

Common

Upper airway cough syndrome (UACS; postnasal drip)

History
Exam
1st investigation
Other investigations

frequent throat clearing, postnasal drip, nasal discharge, nasal obstruction or sneezing typical, halitosis

mucopurulent secretions in the nasopharynx and oropharynx or cobblestone appearance of posterior oropharynx

  • therapeutic trial:

    response to empirical therapy with antihistamine and decongestant

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    Asthma

    History
    Exam
    1st investigation
    Other investigations

    wheezing, chest tightness, dyspnoea, symptom variability, strong family history of asthma/atopic disease, cough, paroxysms, exacerbation by irritants or seasonal exposures; cough may sometimes be the principal or sole symptom, usually worse at night (cough-variant asthma)[10]

    wheezing and prolonged expiratory phase on pulmonary examination

    • spirometry with bronchodilator:

      FEV1/FVC ratio is the primary diagnostic test

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    • peak expiratory flow rate (PEFR):

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

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    • fractional exhaled nitric oxide (FeNO):

      elevated (>40 parts per billion)

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    • other non-invasive airway inflammation biomarkers (blood and sputum eosinophil counts and eosinophilic cationic protein):

      elevated

    • therapeutic trial:

      improvement in symptoms following a 2-4 week course of an inhaled corticosteroid or a leukotriene receptor antagonist

    • bronchoprovocation testing:

      provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) <4 mg/mL

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    • FBC:

      normal or elevated eosinophils and/or neutrophilia

    • serum IgE antibodies:

      elevated antigen-specific IgE antibodies

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    • skin-prick allergy testing:

      may be positive for allergen

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    Gastro-oesophageal reflux disease (GORD)

    History
    Exam
    1st investigation
    Other investigations

    heartburn, dysphagia, acid regurgitation, association of cough with slouched posture, phonation, rising from bed, or eating suggest reflux disease; may be silent[38][41]

    no differentiating features on examination, may be overweight or obese

    • therapeutic trial of proton-pump inhibitors (PPIs) for 8 weeks:

      relief of symptoms

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    • 24-hour oesophageal pH monitoring:

      pH <4 for 4% or more of monitoring time and coinciding with cough is consistent with pathological acid exposure

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    • barium oesophagram:

      reflux

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    Non-asthmatic eosinophilic bronchitis (NAEB)

    History
    Exam
    1st investigation
    Other investigations

    chronic non-productive cough; no differentiating features on history

    no differentiating features on examination

    • sputum or broncho-alveolar lavage (BAL) differential count:

      eosinophilia

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    • FeNO:

      elevated

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    • therapeutic response to inhaled steroids:

      present

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    Chronic bronchitis/COPD

    History
    Exam
    1st investigation
    Other investigations

    history of smoking may be present; cough may produce sputum; dyspnoea, especially exertional, may accompany the cough

    mild cases: most respiratory examinations are normal, may show quiet breath sounds, prolonged expiratory phase, rhonchi, or wheezes; advanced cases: cyanosis, barrel chest, use of accessory muscles of inspiration, increased S2 over left sternal border, or peripheral oedema

    • pulmonary function tests:

      decreased FEV1, FEV1/FVC <70%, residual volume >120%, total lung capacity >120%, diffusion capacity for CO <80%

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    • chest x-ray:

      hyperinflation, but may not be present in some cases

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    Angiotensin-converting enzyme inhibitor (ACE inhibitor)

    History
    Exam
    1st investigation
    Other investigations

    dry cough, typically associated with tickling or scratching sensation in the throat; cough may begin within days or months of initiating ACE inhibitor therapy

    no specific examination findings

    • stop ACE inhibitor use:

      resolution of cough

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      Pneumonia

      History
      Exam
      1st investigation
      Other investigations

      fever, malaise, cough, usually productive of sputum, chest pain[27]

      dullness to percussion, decreased breath sounds, and presence of rales

      • chest x-ray:

        infiltrate suggestive of pneumonia

      • WCC (blood):

        usually elevated but non-specific

      • serum C-reactive protein (CRP):

        may be elevated

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      • sputum Gram stain and culture:

        presence of micro-organisms and leukocytes in a good sputum sample (<25 squamous epithelial cells per field) supports the diagnosis of respiratory tract infection

      Post-infectious cough

      History
      Exam
      1st investigation
      Other investigations

      cough of duration between 3 and 8 weeks following symptoms of acute respiratory infection; nasal/sinus congestion, non-purulent nasal discharge, sore throat[57]

      diagnosis is clinical and one of exclusion

      • chest x-ray:

        normal, rules out pneumonia

      • WCC (blood):

        usually elevated but non-specific

      • sputum Gram stain and culture:

        presence of micro-organisms and leukocytes in a good sputum sample (<25 squamous epithelial cells per field) supports the diagnosis of respiratory tract infection

      Bordetella pertussis infection

      History
      Exam
      1st investigation
      Other investigations

      paroxysms of cough, post-tussive vomiting, or inspiratory whooping sound; more likely if local epidemiology suggests increased prevalence

      petechiae and conjunctival haemorrhages may result from cough paroxysms; lung examination is typically normal

      • nasopharyngeal culture (if symptoms <2 weeks):

        positive

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      • polymerase chain reaction, and/or serology (if symptoms present >4 weeks):

        positive

      Uncommon

      Lung cancer

      History
      Exam
      1st investigation
      Other investigations

      history of tobacco smoking, change in character of chronic cough, haemoptysis, hoarseness, chest pain, weight loss, superior vena cava syndrome (localised oedema of face and upper extremities, facial plethora, distended neck and chest veins), symptoms related to distant metastases and advanced stages of cancer

      central lung cancers may cause unilateral localised wheezing; superior vena cava syndrome; cachexia and symptoms related to distant metastases (e.g., bone pain) are late symptoms

      • chest x-ray:

        presence of the lesion

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      • CT chest:

        presence of the lesion and loco-regional disease

      • sputum cytology:

        may document presence of malignant cells

      • bronchoscopy:

        presence of tumour

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      Bronchiectasis and chronic suppurative lung disease

      History
      Exam
      1st investigation
      Other investigations

      cough productive of large amounts of mucopurulent sputum, diurnal variation (e.g., worse in the morning), positional worsening; dyspnoea, wheezing, haemoptysis; paroxysmal cough non-productive of sputum may sometimes be present

      crackles and wheezing, predominantly over lower lobes; clubbing in a minority of patients

      • chest x-ray:

        increased bronchovascular markings

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      • high-resolution CT chest:

        bronchial dilatation, size of the bronchi exceeding the size of the accompanying artery, lack of tapering of the bronchi at the lung peripheries[55]

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      • pulmonary function tests:

        irreversible obstructive defect, with FEV1/FVC <70%

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      Interstitial pulmonary fibrosis

      History
      Exam
      1st investigation
      Other investigations

      dyspnoea of sub-acute onset dominates the clinical picture; cough typically dry

      dry, velcro crackles, typically over lung bases; clubbing may be present

      • chest x-ray:

        increased interstitial markings

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      • high-resolution CT chest:

        interstitial pneumonitis: patchy, predominantly basilar and sub-pleural reticular changes with honeycombing and traction bronchiectasis in later stages of the disease

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      • pulmonary function tests:

        restrictive pattern with total lung capacity <80%, functional residual capacity <80%, and vital capacity <80%, with diffusion capacity for CO <80%

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      • biopsy:

        pattern of usual interstitial pneumonia

      Sarcoidosis

      History
      Exam
      1st investigation
      Other investigations

      most patients asymptomatic; symptomatic patients: shortness of breath, dyspnoea on exertion, and chest pain are present in minority of patients; low-grade fever; other symptoms reflect involvement of various organs

      most often normal; skin lesions (erythema nodosum and maculopapular skin lesions), enlargement of lacrimal glands, lymphadenopathy in cervical, supraclavicular, or axillary areas; redness of eye, tearing, and photophobia may represent uveitis

      • chest x-ray:

        various findings, bilateral hilar and mediastinal lymphadenopathy, reticular infiltrates; fibrosis with decreased lung volumes in late sarcoidosis

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      • chest CT with high-resolution cuts:

        bilateral hilar and mediastinal lymphadenopathy, interstitial infiltrates

      • pulmonary function tests:

        often normal, but may show non-specific reduction in diffusion capacity, obstruction, restriction, or mixed picture

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      • bronchoscopy with biopsy:

        non-caseating granuloma is supportive, but other granulomatous disorders should be reasonably excluded with special stains and clinical assessment

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      Tuberculosis (TB)

      History
      Exam
      1st investigation
      Other investigations

      residence in/visit to high-prevalence area; immunosuppressed status (e.g., HIV infection, immunosuppressant medication, transplant recipients, diabetes, dialysis treatment); epidemiological risk factors, particularly close contact with active TB; history of anorexia, malaise, weight loss, fever, or night sweats; chronic cough productive of sputum, occasionally associated with haemoptysis

      fever, cachexia, tachycardia; asymmetry in chest movement and dullness to percussion due to pleural effusion, bronchial breathing, crackles, rales due to an infiltrate or rhonchi in presence of significant bronchial purulence; palpable extra-thoracic lymphadenopathy is uncommon

      • chest x-ray:

        primary TB: mid-lung infiltrate; secondary TB: predominantly upper lobe infiltrates with distinct tendency for fibrosis and volume loss

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      • sputum Gram stain and culture:

        presence of acid-fast bacilli (Ziehl-Neelsen stain) in sputum or broncho-alveolar lavage (BAL)

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      • nucleic acid amplification tests (NAAT):

        positive for M tuberculosis

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      • tuberculin skin test:

        positive

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      • interferon-gamma release assays:

        positive

        More
      • lateral flow urine lipoarabinomannan (LF-LAM) assay:

        positive

        More

      Zenker’s diverticulum

      History
      Exam
      1st investigation
      Other investigations

      dysphagia present in 98% of patients; regurgitation of bland undigested food; frequent aspiration; noisy deglutition (gurgling); halitosis; voice changes

      halitosis, voice changes

      • barium oesophagram:

        positive contrast within the structure connected to the posterior wall of oesophagus is consistent with a diverticulum

      • endoscopy:

        visualisation of diverticulum

      Thoracic aortic aneurysm (TAA)

      History
      Exam
      1st investigation
      Other investigations

      most patients have no symptoms attributable to TAA at the time of diagnosis; most common initial symptom is vague pain, which can occur in the chest, back, flank, or abdomen; hoarseness due to stretching or compression of left recurrent laryngeal nerve; tracheal deviation, persistent cough, or other respiratory symptoms such as shortness of breath or chest pain; dysphagia (uncommon) due to compression of the oesophagus by the aneurysm; sudden and catastrophic haemoptysis or haematemesis; neurological deficits including paraplegia

      generally no obvious physical findings in chest area unless tracheal deviation is present; patients with an abdominal component may have a pulsatile abdominal mass similar to pure abdominal aortic aneurysms; signs of arterial perfusion differentials in both upper and lower extremities; evidence of visceral ischaemia; focal neurological deficits; murmur of aortic regurgitation; bruits

      • chest radiograph:

        widened mediastinum, prominence of the aortic knob, or tracheal deviation

      • spiral CT of chest with three-dimensional reconstructions:

        visualisation of aneurysm, seen as an increase in size of a section of the aorta

      • MRI and magnetic resonance angiography:

        visualisation of aneurysm, seen as an increase in size of a section of the aorta

      Foreign body

      History
      Exam
      1st investigation
      Other investigations

      abrupt onset, more common in young children

      may be asymptomatic or show signs of airways obstruction, including cough, wheeze, decreased breath sounds, dyspnoea, or fever

      • laryngoscopy/bronchoscopy:

        visualisation of foreign body

      • chest x-ray:

        visualisation of foreign body (if object is radio-opaque)

      • chest CT:

        visualisation of foreign body

      Hypersensitivity pneumonitis

      History
      Exam
      1st investigation
      Other investigations

      occupational/environmental exposure to allergens (e.g., farmers, bird breeders), progressive dyspnoea, fatigue, and weight loss

      clubbing, increased respiratory rate, inspiratory crackles over lower lung fields

      • chest x-ray:

        fibrotic changes; loss of lung volume particularly affecting the upper lobes

      • chest CT:

        features of fibrosis

      • IgG testing:

        high titres with antigen-specific antibodies

      Bronchiolitis

      History
      Exam
      1st investigation
      Other investigations

      age <1 year, cough, wheeze, and dyspnoea, history of prematurity, underlying cardiopulmonary disease or immunodeficiency

      high respiratory rate, accessory muscle use, retractions, wheezes, crackles, purulent secretions on bronchoscopy

      • chest x-ray:

        consolidation and atelectasis in severe disease

      • virology:

        may be positive for respiratory syncytial virus

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      • high-resolution CT scan:

        signs of small airways disease

      Recurrent aspiration

      History
      Exam
      1st investigation
      Other investigations

      dysphagia, association of cough with eating/drinking, fear of choking with eating/drinking; may have history of neurological disease including stroke, multiple sclerosis, Parkinson's disease

      signs of neurological disease such as stroke, multiple sclerosis, Parkinson's disease

      • chest x-ray:

        persistent lower lobe infiltrates

      • swallow evaluation:

        aspiration

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        Tropical filarial pulmonary eosinophilia

        History
        Exam
        1st investigation
        Other investigations

        travel to endemic area (sub-Saharan Africa, Indian subcontinent, southeast Asia, Oceania); dry, paroxysmal cough, frequently nocturnal

        frequently normal; wheezing, rhonchi, crackles may be present on lung exam; some patients develop hepatosplenomegaly

        • blood count with differential:

          eosinophilia

        • chest x-ray:

          increased interstitial markings

        • filarial antibody levels:

          elevated

        • serum IgE:

          elevated

        Somatic cough syndrome (psychogenic cough)

        History
        Exam
        1st investigation
        Other investigations

        extensive evaluation has ruled out other causes

        cough improves following behaviour modification or psychiatric therapy

        • none:

          extensive evaluation has already ruled out other causes

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