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Stephen Chapman

, Grace Robinson

, John Stradling

, Sophie West

, and John Wrightson

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date: 01 July 2022

Clinical assessment and causes

Physiological mechanisms of breathlessness

Dyspnoea refers to the abnormal and uncomfortable awareness of breathing. Its physiological mechanisms are poorly understood; possible afferent sources for the sensation include receptors in respiratory muscles, juxtacapillary (J) receptors (sense interstitial fluid), and chemoreceptors (sensing ↑CO2 and ↓O2).

Clinical assessment

All patients need a full history and examination. Key points in the assessment are:

  • Duration and onset of breathlessness. Box 1.1 groups the causes of breathlessness by speed of onset, although, in practice, some variability and overlap exist. Patients often underestimate the duration of symptoms—enquiring about exercise tolerance over a period of time is a useful way of assessing duration and progression

  • Severity of breathlessness. Assess the level of handicap and disability by asking about effects on lifestyle, work, and daily activities

  • Exacerbating factors. Ask about rest and exertion, nocturnal symptoms, and body position. The timing of nocturnal breathlessness may provide clues to the likely cause: left ventricular failure (LVF) causes breathlessness after a few hours of sleep and resolves after about 45min; asthma tends to occur later in the night; laryngeal inspiratory stridor causes noisy breathlessness of very short duration (<1min); and Cheyne–Stokes apnoeas result in breathlessness that is recurrent and clears each time in <30s. Orthopnoea is suggestive of LVF or diaphragm paralysis, although it is also common in many chronic lung diseases. Breathlessness during swimming is characteristic of bilateral diaphragm paralysis. Trepopnoea refers to breathlessness when lying on one side as a result of ipsilateral pulmonary disease

  • Associated symptoms, such as cough, haemoptysis, chest pain, wheeze, stridor, fever, loss of appetite and weight, ankle swelling, and voice change. Wheeze may occur with pulmonary oedema, pulmonary embolism (PE), bronchiolitis, and anaphylaxis, in addition to asthma and chronic obstructive pulmonary disease (COPD)

  • Personal and family history of chest disease

  • Lifetime employment, hobbies, pets, travel, smoking, illicit drug use, medications

  • Examination of the cardiovascular and respiratory systems. Observe the pattern and rate of breathing. Assess for signs of respiratory distress. Look for paradoxical abdominal movement if the history suggests diaphragmatic paralysis. A useful bedside test is to exercise the patient (e.g. by stepping on and off a 15–20cm block) until their breathlessness occurs, and then measure oximetry immediately on stopping when the finger is still; a fall in O2 saturation is expected with organic causes of dyspnoea.


Initial investigations typically include resting oximetry, peak flow and spirometry, CXR, and ECG. Further tests depend on clinical suspicion; options include full pulmonary function tests (PFTs) with measurement of lung volumes lying and standing, gas transfer and flow–volume loop, bronchial hyperresponsiveness or reversibility testing, maximal mouth or inspiratory sniff pressures, arterial blood gases (ABGs) (with measurement of alveolar to arterial (A–a) gradient (see Breathlessness p. [link]), exercise oximetry, ventilation-perfusion (V/Q) scanning and computed tomographic pulmonary angiography (CTPA), high-resolution CT (HRCT), blood tests (FBC and TSH), echocardiogram (echo), exercise ECG, and cardiac catheterization.

Specific situations

Causes of breathlessness with a normal CXR

  • Airways disease (asthma, upper airways obstruction, bronchiolitis)

  • Pulmonary vascular disease (PE, idiopathic PHT, intrapulmonary shunt)

  • Early parenchymal disease (e.g. sarcoid, interstitial pneumonias, infection—viral, Pneumocystic jirovecii pneumonia (PCP))

  • Cardiac disease (e.g. angina, arrhythmia, valvular disease, intracardiac shunt)

  • Neuromuscular weakness

  • Metabolic acidosis

  • Anaemia

  • Thyrotoxicosis

  • Hyperventilation syndrome.

Causes of episodic/intermittent breathlessness

  • Asthma

  • Pulmonary oedema

  • Angina

  • PE

  • HP

  • Vasculitis

  • Hyperventilation syndrome.

Distinguishing cardiac and respiratory causes of breathlessness

This can be difficult. Many of the clinical features of left heart failure are non-specific and easily confused with respiratory disease (e.g.orthopnoea, wheeze). In chronic cardiac failure, crackles on auscultation and radiological features of pulmonary oedema may be absent, even when the pulmonary capillary wedge pressure is significantly raised (due to adaptive changes from vascular remodelling). The presence of emphysema may also render crackles inaudible and lead to atypical CXR appearances of pulmonary oedema. Chronic left heart failure commonly leads to a restrictive ventilatory defect and reduced gas transfer on PFTs and may also result in PHT. HRCT features of left heart failure include septal and peribronchovascular interstitial thickening, ground-glass shadowing, pleural effusions, and cardiomegaly. Resting ECG is useful—in practice, a cardiac cause of breathlessness is unlikely in the setting of a completely normal ECG. Exercise ECG, echo, and cardiac catheterization may be required. Elevated natriuretic peptide levels predict the likelihood of heart failure as well as the prognosis from this condition. Cardiac and respiratory diseases can, of course, coexist.