Dyspnoea (chronic)

Overview

• Dyspnoea is a subjective sensation of breathing discomfort, described as varying in intensity and quality. 1
• It arises from a complex interplay of physiological, psychological, social and cultural factors, shaped by individual perception and experience 1
• Dyspnoea is considered chronic when it persists for greater than 4 to 8 weeks. 2
• Chronic dyspnoea may result from an underlying pathological condition, or it may present without any identifiable organic cause 3
• Chronic dyspnoea usually occurs mostly due to cardiac or respiratory causes, however, there is wide range of differential diagnosis 4, 5
  • Cardiac causes: congestive cardiac failure, ischaemic heart disease, arrhythmia, valvular and structural disease, pericardial effusion, constrictive pericarditis
  • Respiratory causes: chronic obstructive pulmonary disease (COPD), asthma, interstitial lung disease (ILD), bronchiectasis, pleural effusion, pulmonary malignancy, pulmonary hypertension
  • Haematological: anaemia
  • Neuromuscular: myopathies, motor neuron disease, myasthenia gravis, diaphragm paresis, chest wall deformity
  • Gastrointestinal: gastro-oesophageal disease (GORD), hiatus hernia, chronic aspiration
  • Metabolic: metabolic acidosis, renal failure, thyroid disease, liver cirrhosis
  • Psychological: anxiety disorder, somatoform disorders
  • Other: physical deconditioning, obesity, pregnancy, upper airway obstruction (compressive tumour)
• The aetiology of dyspnoea may not be obvious and so requires clinical history, physical examination, clinical biomarkers, and imaging to identify a diagnosis 3
• Basic initial workup includes blood tests (full blood count, thyroid function test, urea and electrolytes, liver function tests) 1
• For suspected heart failure causing dyspnoea, do Brain Natriuretic Peptide (BNP) and troponin as these are less expensive and more accessible than echocardiography. 4
  • BNP is useful in diagnosis and management of heart failure, and has very high negative predictive value 6
• For other suspected cardiovascular causes the following investigations are useful:
  • ECG: a useful test to identify ischaemic changes, conductive issues in heart or signs of left ventricular hypertrophy 6
    • If ongoing concerns of arrhythmias or conduction issues, then perform continuous monitoring with Holter Monitoring or loop recorder 6
  • Transthoracic echocardiogram: provides information on systolic and diastolic function, valvular pathology and estimates pulmonary artery pressures 6
    • If valvular pathology, particularly regurgitant disease needs to be investigated further then transesophageal echocardiogram can be performed 6
  • Stress testing: pharmacological (dobutamine) given for evaluation of ischaemic heart disease or assessing severity of aortic stenosis 6
  • CT coronary angiogram: recommended first line investigation of coronary artery disease when patient is symptomatic 6
  • Cardiac MRI: evaluates both left and right ventricular function, detects myocardial ischemia, identifies infiltrative disease (sarcoidosis, amyloidosis) 6
    • Cardiac MRI provides details of right heart size and function, which is beneficial for evaluating pulmonary hypertension 6
  • CT invasive angiogram: performed when coronary artery disease is suspected (either seen on CT coronary angiogram or ischemia on cardiac MRI) 6
  • Right-heart catheterisation: diagnostic test for pulmonary hypertension 6
• Traditional management of dyspnoea includes interventions like bronchodilators, exercise training, ambulatory oxygen, inspiratory muscle training and opiate medications 7

• A chest radiograph (CXR) is often recommended as an initial investigation following clinical assessment in patients to differentiate between cardiac and respiratory causes of dyspnoea 4, 8
• CXR is inexpensive, readily available, and involves low radiation dose, however it has limited sensitivity 8, 9
• In patients with chronic dyspnoea, CXR was able to identify features to further investigate and diagnose interstitial lung disease (ILD), chronic obstructive pulmonary disease (COPD), and heart failure: 4
  • Findings suggestive of COPD (mainly emphysema) include hyperlucent lung fields, flattening of diaphragm, widening of intercostal spaces, and narrowed and more vertical cardiac silhouette 9
    • In chronic bronchitis, bronchial wall thickening can be seen, though this remains a clinical diagnosis 10
  • ILD can show reticular changes (hazy opacities) in later stage of the disease, however, early fibrosis is often missed and requires further imaging with HRCT for better evaluation 11
  • CXR has low sensitivity (~67%) in diagnosis of heart failure, hence, further investigation is needed with echocardiogram or lung ultrasound 12
    • Radiographic signs of pulmonary congestion include vascular redistribution (prominent hilum, upper lobe vein enlargement, widened vascular pedicle); other signs of heart failure include Kerley B lines (interstitial oedema), bat wing pattern (alveolar oedema), pleural effusions and cardiomegaly 12
• Clinician’s history, physical examination and CXR were accurate 66% of time when compared with final diagnosis 13
  • The accuracy improved to 81% in patients with asthma, COPD, ILD or cardiomyopathy 13
  • The accuracy decreased to 33% for less common causes of chronic dyspnoea 13
• CXR's diagnostic accuracy can vary based on radiologist expertise and quality of image 12

• Spirometry is useful to differentiate the underlying cause of dyspnoea, monitor disease progression of chronic respiratory function, and evaluate effectiveness to therapeutic interventions 14
• It is an initial diagnostic tool for suspected respiratory airway disease, particularly COPD and asthma 4
• Abnormal spirometry findings have shown to aid diagnosis in 33% of chronic dyspnoea patients 4
• Spirometry measures the following:
  • Forced vital capacity (FVC): the total amount of air that can be expelled from full lungs 14
  • Forced expiratory volume in 1 second (FEV1): the amount of air expelled in 1 second during the above manoeuvre 14
  • FEV1/FVC ratio: if reduced, indicates an obstructive cause; if preserved, indicates a restrictive cause 14
• A decreased FEV1/ FVC ratio (<0.7) indicates obstructive disease 1
  • Causes of obstructive disease can be classified into the following:
    • Reversible: asthma
    • Irreversible: COPD
    • Mixed (partially reversible/ variable component): bronchiectasis, cystic fibrosis, silicosis (early), alpha-1-antitrypsin deficiency 14
  • For an obstructive picture, reversibility testing should be done with short-acting bronchodilator to differentiate between asthma and COPD 14
    • An increase in FEV1 by >12% and >200mL post-bronchodilator supports a diagnosis of asthma 15
  • Bronchoprovocation testing can be undertaken in chronic dyspnoea due to asthma when there is a normal spirometry 4
  • In smokers, there can be normal pulmonary function testing (~4.7%) however their CT chest will show significant air trapping signifying emphysema 16
  • When there is diagnostic uncertainty from spirometry, pulmonary function testing should be performed with consideration of CT chest 9, 16, 17
• A reduced FVC and either a normal or increased FEV1/FVC ratio is suggestive of restrictive disease 1
  • Causes of restrictive disease can be classified into the following:
    • Extrapulmonary: obesity, kyphoscoliosis 14
    • Parenchymal lung disease: interstitial lung disease, (including asbestosis, eosinophilic pneumonia, hypersensitive pneumonitis, idiopathic pulmonary fibrosis, sarcoidosis, silicosis) 14
    • Neuromuscular disorders: Guillain Barre syndrome, muscular dystrophy, myasthenia gravis, amyotrophic lateral sclerosis 14
  • Spirometry alone is insufficient to differentiate types of restrictive disease and needs further evaluation using full lung volumes/ pulmonary function testing, imaging and possibly a biopsy 18
  • Mean inspiratory pressure (MIP) and mean expiratory pressure (MEP) can be used to investigate neuromuscular diseases for restrictive disease with normal CT of lungs 19
• A decreased FVC and decreased FEV1/FVC ratio is classified as mixed defect 14
• Full pulmonary function testing is recommended in patients with restrictive or mixed pattern: 14
  • This includes measuring total lung capacity (TLC) and diffusing capacity of carbon monoxide (DLCO) 14
  • The fraction of exhaled nitric acid (FeNO) is a non-invasive biomarker of eosinophilic inflammation and used for diagnosis of asthma, treatment choices, and changes required for symptom control 20
• Spirometry with flow volume loop is used in assessment of upper airway obstruction (such as multinodular goitre, tracheobronchomalacia tracheal stenosis, extensive dynamic airway collapse (EDAC)): 21
  • Upper airway obstruction can be misdiagnosed as COPD and asthma 21
  • There is high sensitivity and specificity in performing flow-volume-loop to diagnose upper airway obstruction 21
  • Other ways to diagnose a patient with suspicion of upper airway obstruction are chest and neck CT, bronchoscopy or laryngoscopy 21
• Spirometry assessment in a patient with history of smoking was useful in diagnosing COPD 13
• In COPD, spirometry is key to confirming the diagnosis, however, is underused worldwide 22
• In primary care practice there are barriers to using spirometry including time, cost, poor technique, lack of trained staff, and difficulty interpreting results 4, 23
• For management of treatment options of asthma and COPD, refer to COPD and Global Initiative for Asthma (GINA) guidelines

• CT is indicated when initial investigations (chest X-ray, spirometry) are non-diagnostic, or when clinical suspicion remains high for underlying structural lung disease, vascular abnormalities, or interstitial pathology 4, 24
• CT with an expiratory phase can detect small airways dysfunction such as air trapping and mosaic attenuation which is useful in diagnosing obliterative bronchiolitis, hypersensitivity pneumonitis, asthma, COPD, respiratory bronchiolitis-associated ILD, and sarcoidosis 3, 32
• CT offers diagnostic value in upper airway disorders causing dyspnoea, such as tracheobronchomalacia or tracheal stenosis that manifest as excessive dynamic airway collapse on imaging 3
• Incidentally, pulmonary oedema and cardiomegaly can be detected on CT chest, however this modality is not recommended for diagnosis of heart failure 4
• In COPD, particular emphysema, CT can detect disease even when spirometry is normal, if features such as air trapping, mucus plugging, and signs of pulmonary hypertension are present 9
• CT provides highest sensitivity and specificity in diagnosing diffuse parenchymal lung disease and can detect early ILD in earlier stages 4, 25
  • CT findings in interstitial lung disease includes linear and reticular pattern, nodular pattern, ground-glass opacities, consolidation, as well as, signs of emphysema and cystic lung disease 25
• High resolution CT (HRCT) is the preferred modality of diagnosing bronchiectasis, though it can be identified on standard CT scans 26
  • Bronchiectasis involves both small and large airways, requiring high resolution imaging for accurate assessment 26
  • Characteristic findings in bronchiectasis include dilated, thick-walled segmental and sub-segmental bronchi best visualised by comparing affected and unaffected lung regions 26
  • Peripheral small airways may appear as tiny centrilobular nodules or tree-in-bud branching patterns, representing mucus plugging or bronchiolar obstruction below CT resolution 26
  • HRCT allows for early and accurate detection of these subtle airway abnormalities, which contribute to chronic dyspnooea 26
• CT pulmonary angiogram (CTPA) is commonly used in diagnosis of acute pulmonary embolism but can be used in cases of suspected chronic thromboembolic pulmonary hypertension (CTEH) 4
• CT imaging involves exposure to ionising radiation, so clinicians must carefully select patients based on age, radiation risk, and expected diagnostic value 4

• Cardiopulmonary testing (CPET) is beneficial in assessing underlying pathophysiological mechanisms of dyspnoea and exercise limitation 27
• CPET, traditionally used for cardiac assessment, is increasingly recognised for discovering the causes of unexplained dyspnoea 28
• CPET provides measurement for the following criteria 29:
  • Oxygen consumption (VO2): volume of oxygen consumed per minute, indexed to bodyweight to reflect aerobic capacity
  • Carbon dioxide production (VCO2): amount of carbon dioxide exhaled per minute
  • VO2 max: maximum oxygen uptake achieved at peak exercise (requires repeated tests for accuracy)
  • Peak VO2: highest uptake of oxygen during presumed maximal exercise effort
  • Respiratory exchange ratio (RER): ratio of carbon dioxide to oxygen uptake (VCO2/ VO2)
  • Minute ventilation (VE): volume of air inhaled or exhaled by lungs per minute
  • Maximum voluntary ventilation (MVV): measure maximal amount of air breathed in and out of lungs every minute during maximal respiratory effort; commonly measured as FEV1 x 40 (from spirometry results)
  • Anaerobic threshold (AT): exercise intensity at which lactate accumulates in blood, indicating a shift to anaerobic metabolism
  • Breathing reserve: difference between maximum voluntary ventilation (MVV) and the peak exercise ventilation (VE) (i.e. MVV – peak VE)
  • Interpretation of different parameters and likely cause:

• CPET can identify co-existent ischaemic heart disease, peripheral vascular disease and arterial hypoxemia 28
• Another use of CPET is to provide prognostic assessment of patients with pulmonary and cardiac disease by estimating surgical risk and time to clinical worsening 28
• In patients with COPD, CPET helps evaluate effectiveness of therapeutic interventions to reduce exertional dyspnoea and improve exercise tolerance, such as oxygen, bronchodilators, and a pulmonary rehabilitation program 28
• Indications for CPET include when dyspnoea does not improve with intervention or when a potential diagnosis is not found 3
• For better interpretation of CPET results and individual risk assessment, the following tests must be done: laboratory tests (FBC, TFTs, glucose, UECs, VBG/ABG) and cardiopulmonary tests (CXR, ECG, BP, spirometry) 30
• CPET involves monitoring ECG, blood pressure and blood sampling through the course of the test 30
• The two ways to perform CPET are by using cycle ergometer or treadmill, but generally cycle ergometer is preferred: 30
  • Cycle ergometer is preferred in patients with deconditioning, obesity and joint problems and is useful for measuring of external work rate 30
  • Treadmill allows for different grade of incline and speed to be used which elicits greater oxygen desaturation and produces higher level of peak oxygen uptake 30
• Contraindications to performing CPET include: acute myocardial infarction within last 5 days, acute myocarditis, severe symptomatic aortic stenosis, uncontrolled heart failure, uncontrolled arrythmia, dissecting aneurysm, and resting oxygen saturation <86% 29
• In patients with a normal CPET, it is likely that they do not have a serious cause of cardiopulmonary cause contributing to their dyspnoea 3
• The likely cause of normal CPET in patients with chronic dyspnoea is attributed to obesity, deconditioning or functional disorder 3, 4
• Invasive cardiopulmonary testing can be offered for further testing to assess haemodynamics in response to exercise 4
• A diagnostic approach including CPET has shown to diagnose the aetiology of persistent unexplained dyspnoea in 75-99% of patients 3
• CPET is cost-effective given it is beneficial in providing a wide-range of differential diagnoses, and helps to facilitate treatment decisions, hence it should be used more frequently 30
• CPET remains underutilised in clinical practice, likely due to practical barriers such as high equipment costs, limited access, inadequate reimbursement, and insufficient training or awareness among healthcare providers, however its use should be encouraged 31