4: Common respiratory investigations

CHAPTER 4
Common respiratory investigations


Abbreviations



AAFB
acid‐alcohol‐fast bacilli
ABG
arterial blood gas
ABPA
allergic bronchopulmonary aspergillosis
ACE
angiotensin converting enzyme
ANCA
anti‐neutrophil cytoplasmic antibodies
AP
artero‐posterior
ARTP
Association for Respiratory Technology and Physiology
ATS
American Thoracic Society
BAL
bronchoalveolar lavage
β‐hCG
β‐human chorionic gonadotrophin
BTS
British Thoracic Society
CAP
community acquired pneumonia
CO
carbon monoxide
COPD
chronic obstructive pulmonary disease
CRP
C‐reactive protein
CSF
cerebrospinal fluid
CT
computed tomography
CTPA
computed tomography pulmonary angiogram
CUS
compressive ultrasound
CXR
chest X‐ray
EBUS
endobronchial ultrasound‐guided biopsy
ECG
electrocardiogram
ECHO
echocardiogram
EEG
electroencephalograph
EGPA
eosinophilic granulomatosis with polyangiitis
ELISA
enzyme‐linked immunosorbent assay
EOG
electro‐oculogram
ERS
European Respiratory Society
ESR
erythrocyte sedimentation rate
EUS
endoscopic ultrasound
FDG
18F Fluorodeoxy glucose
FeNO
exhaled nitric oxide
FEV
forced expiratory volume
FEV1
forced expiratory volume in 1 second
FNA
fine needle aspiration
FRC
functional residual capacity
FVC
forced vital capacity
GPA
granulomatosis with polyangiitis
HAP
hospital acquired pneumonia
HIV
human immunodeficiency virus
HLA
human leukocyte antigen
HRCT
high‐resolution computed tomography
IgE
immunoglobin E
IGRA
interferon gamma release assay
IH
idiopathic hypersomnia
INR
international normalised ratio
KCO
transfer coefficient
LDH
lactate dehydrogenase
MPO
myeloperoxidase
MRI
magnetic resonance imaging
MRPA
magnetic resonance pulmonary angiogram
MSLT
multiple sleep latency test
MTB
mycobacterium tuberculosis
MVV
maximal voluntary ventilation
NICE
National Institute for Health and Care Excellence
NREM
non‐rapid eye movement
NSIP
non‐specific interstitial pneumonia
O2
oxygen
OSA
obstructive sleep apnoea
PCR
polymerase chain reaction
PE
pulmonary embolus
PEF
peak expiratory flow
PET
positron emission tomography
PPD
purified protein derivative
PTH
parathyroid hormone
pCO2
partial pressure of carbon dioxide in blood
pO2
partial pressure of oxygen in blood
RAST
radioallergosorbent test
REM
rapid eye movement
RV
residual volume
RVC
relaxed vital capacity
SIADH
syndrome of inappropriate anti‐diuretic hormone
SMWT
six‐minute walk test
SUV
standardised uptake value
SWT
shuttle walk test
TBNA
transbronchial lymph node aspiration
TLC
total lung capacity
TLCO
carbon monoxide transfer factor
TST
tuberculin sensitivity test
VA
alveolar gas volume
VATS
video‐assisted thoracoscopy
VC
vital capacity
VE
exercise ventilation
VQ
ventilation perfusion scan
ZN
Ziehl‐Neelsen stain

Laboratory tests


Blood tests can be helpful in the diagnosis of several respiratory conditions and in excluding other conditions. A full blood count is a basic blood test that is conducted in most patients who present to hospital with acute respiratory symptoms and in many patients who present to the outpatient department. Although rarely diagnostic alone, the results can be helpful when interpreted with the results of other investigations.


Patients with chronic anaemia (low haemoglobin) can present with breathlessness as the oxygen‐carrying capacity of the blood is reduced. Anaemia can also exacerbate underlying lung disease. Primary polycythaemia rubra vera, a myeloproliferative disease associated with the JAK2 gene mutation, results in a haemoglobin greater than 18 g dl−1 and a haematocrit of over 55%. Relative polycythaemia can occur secondary to dehydration. Secondary polycythaemia occurs as a physiological response to chronic hypoxaemia; there is an increase in the production of erythropoietin which stimulates the bone marrow to produce more red blood cells. This can occur in those living at high altitudes as part of adaptation and in those with any chronic lung disease, including chronic obstructive pulmonary disease (COPD), pulmonary hypertension, obstructive sleep apnoea (OSA), and carbon monoxide poisoning. It can also be associated with certain haemoglobinopathies, renal cell cancer, liver tumours, and von Hippel‐Lindau disease.


Haemoglobin electrophoresis can confirm the diagnosis of a haemoglobinopathy, for example, sickle cell disease. Sickle cell crisis can result in an acute, life‐threatening chest syndrome, which is discussed in Chapter 17. Haemoglobinopathies are a common cause of pulmonary hypertension, which is discussed in Chapter 11.


The white cell count may be elevated in patients with an acute infection, such as upper or lower respiratory tract infection, and acute sinusitis. The differential cell count can give important clues as to the underlying condition. The neutrophil count may be increased with bacterial infections, steroid therapy, and inflammatory diseases. The white cell count may be reduced with bone marrow suppression secondary to chemotherapy and with severe infection. Patients with neutropenia are at increased risk of respiratory tract infections. Neutropenia with a neutrophil count of less than 1 mmol/L predisposes to life‐threatening sepsis.


A raised lymphocyte count in peripheral blood may be due to viral infection or Mycobacterium tuberculosis (MTB) infection. A low CD4 lymphocyte count is associated with human immunodeficiency virus (HIV) which predisposes to several respiratory tract infections, including pneumocystis jerovicii and is discussed in Chapter 8. Peripheral blood eosinophilia could be due to asthma, allergic conditions, eosinophilic granulomatosis with polyangiitis (EGPA) and parasitic infections. Causes of eosinophilia are discussed in Chapter 7.


A raised C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) can occur with any systemic infection, but may be raised with other inflammatory conditions, including rheumatological conditions and malignancy. Blood cultures should be taken in any patient who presents with symptoms and signs of sepsis, including those with severe community or hospital acquired pneumonia.


Measurements of urea, creatinine, and electrolytes are routinely done. Hyponatraemia may be associated with a syndrome of inappropriate anti‐diuretic hormone (SIADH) which may be associated with small cell lung cancer (Chapter 9). Renal failure can occur in several respiratory/renal syndromes; eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA) and Goodpasture’s syndrome. If these conditions are suspected, anti‐neutrophil cytoplasmic antibodies (ANCA) should be checked. These vasculitic conditions are discussed in Chapter 11. Patients with parenchymal lung disease of unknown cause or with CT showing non‐specific interstitial pneumonia (NSIP) should have investigations for collagen vascular diseases, which will include an autoantibody screen. Liver function tests must be monitored in patients on antifungal drugs, such as itraconazole and voriconazole, and those on Azithromycin when used as a prophylactic antibiotic. Transient increase in alanine transaminase and alkaline phosphatase are often found in patients taking antibiotics.


A d‐dimer test is often done as one of the investigations for suspected pulmonary embolus (PE), but this has low specificity as it is raised in many conditions, including malignancy, infection, and pregnancy. Therefore, it is only useful when it is negative. The role of d‐dimer in diagnosing a PE is discussed in Chapter 11. Troponin levels may be elevated in severe PE because of right heart strain.


Raised corrected calcium is commonly seen in patients with lung cancer who have metastases to bone, and in squamous cell lung cancer due to exogenous parathormone secretion (see Chapter 9). Raised corrected calcium is seen in 10–20% of patients with active sarcoidosis because activated macrophages in the lung and lymph nodes synthesise vitamin D which increases calcium absorption in the gut. Patients with active sarcoidosis may have raised serum angiotensin converting enzyme (ACE) levels. This is not diagnostic of sarcoidosis but can be useful when monitoring response to treatment. Sarcoidosis is discussed in Chapter 7.


Various immunological tests are used to determine if there is immune deficiency in adults and children presenting with recurrent respiratory infections. Patients with bronchiectasis should have measurements of their immunoglobulins, including IgG subclasses (see Chapter 12). Mannose‐binding lectin deficiency and defective anti‐pneumococcal polysaccharide antibody response can predispose to recurrent respiratory infections.


Human immunodeficiency virus (HIV) infection can be the cause of recurrent respiratory tract infections and increases the risk of Mycobacterium tuberculosis infection. It is recommended that patients presenting with frequent or recurring respiratory infections, and those presenting with Mycobacterium tuberculosis infection, have an HIV test (see Chapter 8).


Patients with allergic asthma will have raised IgE levels, and those with high levels above 700 units ml−1 may benefit from treatment with Omalizumab (Xolair), a recombinant IgG1monoclonal antibody. IgE levels will also be greatly elevated in allergic bronchopulmonary aspergillosis (ABPA). In patients with asthma, a radioallergosorbent test (RAST) can be used to confirm an immune response to a specific allergen, for example, cat or house dust mite. Avian precipitants will be positive in patients who have hypersensitivity pneumonitis secondary to exposure to antigens from birds, including pigeons, parrots, and budgerigars.


Theophylline is used in the management of acute and chronic asthma and COPD, and is usually given at a dose of 400 mg daily. Theophylline has a narrow therapeutic range between 10 and 20 mg l−1, with significant side effects if blood levels are high; therefore, levels should be monitored. Theophylline is metabolised in the liver by the cytochrome P450 system and therefore drug interactions are important (see Chapter 3).


A lymphoproliferative disorder is always in the differential diagnosis in patients presenting with lymphadenopathy, including bilateral hilar lymphadenopathy and an anterior mediastinal mass (see Chapter 16). In lymphoma, lactate dehydrogenase (LDH) will be increased. Tumour markers too may be helpful in the investigation of an anterior mediastinal mass. The β‐human chorionic gonadotrophin (β‐hcg) level may be elevated in those with a teratoma, which could be one of the causes of an anterior mediastinal mass (see Chapter 16).


A gamma‐interferon test (QuantiFERON) is an important investigation in the diagnosis of Mycobacterium tuberculosis. This is discussed in Chapter 8.


There is evidence that Vitamin D is important in protecting against respiratory tract infections, including MTB infection. Measurement of 1, 25‐dihydroxycholecalciferol levels, the active form of the vitamin, should be done in patients with recurrent infections and in those diagnosed with MTB. Supplementation should be offered to those found to have levels less than 50 nmol l−1.


Arterial blood gas (ABG) measurements are essential in managing many respiratory conditions which present with respiratory failure. The interpretation of ABG is discussed in Chapter 13.


Sputum tests can be useful in the diagnosis of respiratory tract infections. Routine sampling of sputum is not recommended in the diagnosis of community acquired pneumonia (CAP) as there is a huge variation in the rate of positivity, from 10–80%. Staphylococcal aureus is easily cultured but haemophilus influenzae is harder to culture. If MTB is suspected, then three samples of sputum should be sent for acid‐alcohol‐fast bacilli (AAFB) and Ziehl‐Neelsen (ZN) stain. If the patient is unable to cough up sputum or is unfit for bronchoscopy, induced sputum can be obtained by getting the patient to inhale hypertonic saline solution which will liquefy the secretions and cause violent coughing. Healthcare workers carrying out this procedure should take adequate precautions by doing it in a negative pressure room and by wearing masks, gowns, and gloves.


Analysis of pleural fluid is an important investigation in the diagnosis of pleural disease and is discussed in detail in Chapter 10. Pleural fluid obtained by aspiration or from pleural drainage must be sent for biochemistry (protein, lactate dehydrogenase and cholesterol), cytology, microbiology, and pH. An exudate suggests that the fluid is secondary to infection or malignancy and further investigations, such as a pleural biopsy, may be required. Tuberculous pleural effusion can be difficult to diagnose because there are very few organisms in the fluid, but a lymphocytic pleural fluid suggests MTB infection. Measurement of polymerase chain reaction (PCR), adenosine deaminase, and interferon‐y levels in pleural fluid can be diagnostic of a Mycobacterium tuberculosis pleural infection. Adenosine deaminase levels above 40 U l −1 is strongly suggestive of MTB. The pH of the fluid can be helpful in the diagnosis of an empyema.


Analysis of cerebrospinal fluid (CSF) for protein, glucose, ZN stain, and culture should be done in patients presenting with miliary tuberculosis as it is essential to diagnose tuberculous meningitis (see Chapter 8). The CSF may appear turbid, with elevated protein and lymphocytes and a very low glucose. Organisms are not often seen in the CSF, but PCR of CSF may be helpful if MTB is suspected.


Measurement of legionella and pneumococcal antigens in the urine of those presenting with CAP is recommended in the NICE guidelines and can guide management (see Chapter 8). This is a specific and sensitive test which remains positive even after treatment with antibiotics has been commenced. Three early morning urine samples are often sent for the diagnosis of MTB, but the yield is low except in genitourinary tuberculosis. Compound 490 may be present in the urine samples of patients with MTB, but further evaluation is required before this test becomes widely available.


Some 30–50% of patients with active sarcoidosis have hypercalciuria which can be measured by collecting a urine sample for 24 hours. If untreated, this may result in renal calculi and nephrocalcinosis. Patients with sarcoidosis who have hypercalcaemia and hypercalciuria may require immunosuppression.


A skin prick test is useful in patients suspected of having an atopic condition, such as asthma, eczema, or urticaria. It is a quick, safe, and inexpensive test compared to measuring allergen‐specific immunoglobin E (IgE). A few drops of purified allergen extract are placed on the flexor surface of the forearm and the tip of a small stylet is pressed into the superficial epidermis through the drop of allergen. A positive reaction is when there is a weal with a surrounding erythematous flare after 15 minutes, and the size of this can be measured in millimetres. The reaction to the allergen is compared to the reaction from a drop of histamine (the positive control) and to a drop of normal saline control solution. An itchy weal will develop at the site of histamine within 10 minutes. This is demonstrated in the supplementary material (www.wiley.com/go/Paramothayan/Essential_Respiratory_Medicine).


The Mantoux test, also known as the tuberculin sensitivity test (TST), is a well‐established investigation for suspected MTB and latent tuberculosis. Thus, 0.1 ml of purified protein derivative (PPD) is injected intradermally in the forearm of the patient and the size of the induration is measured after 48–72 hours. Individuals who have had the BCG vaccination will show a mild skin reaction at the site of injection. The Mantoux test is demonstrated in the supplementary material. The result of the Mantoux test must be interpreted carefully together with the results of the Interferon gamma release assay (IGRA), the clinical presentation of the patient, and the CXR, as discussed in Chapter 8.


Imaging of the lung


Chest X‐ray (CXR) (Figure 4.1) is one of the commonest investigations undertaken. Although it lacks the sensitivity and specificity of more sophisticated imaging techniques, it is quick and easy to do, available in all hospitals, and relatively cheap, with only a low dose of radiation exposure. If an abnormality is found, it is important to review old CXRs if possible as some abnormalities may be due to previous infection, scarring, or surgery.

Diagram of normal PA CXR with numbers 1─15 indicating right clavicle (1), left clavicle (2), trachea (3), carina (4), right diaphragm (5), left diaphragm (6), right lung (7), left lung (8), right heart border (9), etc.

Figure 4.1 Diagram of normal PA CXR with labels of structures.


An erect, postero‐anterior (PA) CXR (Figure 4.2) taken with the arms fully abducted, in full inspiration, with the X‐ray beam travelling from back to front, will give optimal images. If the patient is unwell and unable to be upright, then an antero‐posterior (AP) CXR can be done. The size of the heart cannot be accurately estimated with an AP CXR. A lateral CXR gives a good view of the structures lying behind the heart and the diaphragm, especially the hilar and perihilar structures which are usually not clear on a PA CXR (Figure 4.3, Figure 4.4).

Image described by caption.

Figure 4.2 Normal PA CXR.

Diagram of normal lateral CXR with structures labeled 1─12 representing thoracic vertebral bodies, scapula, pulmonary trunk and hilum, descending aorta, head of clavicle, trachea, aortic arch, etc.

Figure 4.3 Diagram of normal lateral CXR with labels of structures.

Image described by caption.

Figure 4.4 Normal lateral CXR.


When reviewing a CXR, it is important to look at it in a systematic way. If the CXR is not rotated, then the medial ends of the clavicles will be symmetrical, and the thoracic spines will appear straight. If the patient has taken a full inspiration and the exposure is adequate, then the lungs will appear black and the vertebral bodies will be visible. In full inspiration, the right hemidiaphragm will be 2 cm higher than the left hemidiaphragm as the liver pushes it up, and it will be intersected by the anterior part of the sixth rib. (Box 4.1) lists the features on the CXR that should be checked. Abnormalities in some areas are often missed; this includes the area behind the heart, the lung apices, the first costochondral junction, and the costophrenic angles.


A normal CXR appears black because the lungs are filled with air. In a normal CXR, the carina will be sharp. Splaying of the carina suggests subcarinal lymphadenopathy or an enlarged left atrium. The hila are composed of the pulmonary arteries, pulmonary veins, bronchi, and lymph nodes. The left hilum is 0.5–1.5 cm higher than the right hilum. The oblique fissure, which is visible in 60% of individuals, separates the upper and lower lobes of the left lung and the middle and lower lobes of the right lung. The horizontal fissure separates the upper and middle lobes of the right lung. The costophrenic angles are normally sharp and well delineated.


A lack of clarity, for example, along the heart borders or the diaphragm, suggests adjacent consolidation or collapse of the surrounding lung and is called the ‘silhouette sign’. In the consolidated lung, air passing through a bronchus will show up against the opaque lung and is called an ‘air bronchogram’. Figure 4.5 shows a CXR of a consolidated lung with an air bronchogram. Pulmonary oedema has the appearance of fluid in the alveoli, fissures and costophrenic angles and the presence of Kerley B lines. There will be areas of sub‐segmental collapse, with atelectasis, linear lines, and horizontal lines. The cardiothoracic ratio may be greater than 50%, suggesting cardiomegaly. With pulmonary oedema, the shadowing starts at both hila and increases towards the periphery of the lungs in a ‘bat’s wing’ distribution. Figure 4.6 shows a CXR with pulmonary oedema.

Image described by caption.

Figure 4.5 CXR showing consolidation left lower lobe with air bronchogram.

Image described by caption.

Figure 4.6 CXR showing pulmonary oedema.


The CXR is often the first investigation to lead to a diagnosis of lung cancer. Abnormalities that suggest lung cancer include a lung mass, lobar collapse, pleural effusion, or a pulmonary nodule. The terms ‘nodule’ and ‘mass” are often used interchangeably but a lesion less than 3 cm should be called a nodule and a lesion larger than 3 cm called a mass.


Features that are suspicious for malignancy include a large size, cavitation, spiculation, and increase in size over time (if previous imaging is available to compare with). The differential diagnoses, investigation, and management of pulmonary masses and pulmonary nodules are discussed in Chapter 9.


Cavitation is an area of radiolucency within a mass and the differential diagnosis includes squamous cell carcinoma, MTB, lung abscess, klebsiella pneumonia, Staphylococcus aureus pneumonia, GPA, and pulmonary infarct. Figure 4.7 shows a cavitating lesion.

Image described by caption.

Figure 4.7 CXR showing a cavitating lesion left lower lobe.


Pulmonary nodules measuring 3–5 mm are called miliary, and the differential diagnosis of miliary nodules includes miliary tuberculosis (Figure 4.8), fungal infections, and chickenpox pneumonia (see Chapter 8).

Image described by caption.

Figure 4.8 CT thorax showing miliary tuberculosis.


Collapse of a lobe of the lung occurs when there is no air entering that lobe, for example, when there is an endobronchial lesion in the bronchus, such as lung cancer, an inhaled foreign body, or even impacted mucus plug. Collapse of a lobe will also result in volume loss and compensatory expansion of the other lobes which results in increased transradiency of the adjacent areas of the lung.


A complete ‘white out’ can occur either due to complete collapse of a lung, a large pleural effusion, extensive consolidation, or a combination of these. When there is complete collapse, the mediastinum (trachea and heart) will shift towards the side of the collapse and with a pleural effusion, the trachea will shift away from the effusion.


The radiological appearance which is characteristic for each lobar collapse is described in Box 4.2.

Jun 4, 2019 | Posted by in RESPIRATORY | Comments Off on 4: Common respiratory investigations
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