Essential respiratory medicine. Shanthi Paramothayan

Chapter 4. Common respiratory investigations

Learning objectives

 To know what investigations are required to make a diagnosis in patients presenting with respiratory symptoms and signs

 To understand how samples of bloods, urine, pleural fluid, cerebrospinal fluid, and sputum can be useful in diagnosing respiratory conditions

 To be able to interpret peak expiratory flow, spirometry and lung function

 To understand the basic principles of imaging of the lung, including the chest X-ray, CT scan, CTPA, VQ scan, thoracic ultrasound, MRI scan, and PET scan

 To understand functional investigations, including the six-minute walk test, the shuttle test, and cardiorespiratory investigations

 To understand of investigations for sleep-related disorders, including overnight oximetry, sleep study, full polysomnography, and the multiple sleep latency test

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 antipneumococcal 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 IgG1mono- clonal 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.

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).

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.

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

Figure 4.2 Normal PA CXR.

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

Figure 4.4 Normal lateral CXR.

Box 4.1 Interpretation of the CXR.

 Correct patient (name and date of birth)

 Date of CXR

 Correct labelling of right and left side

 Symmetry: medial ends of both clavicles and thoracic spines

 Adequate exposure: vertebral bodies visible

 Shape and bony structures of the chest wall

 Position of trachea

 Mediastinal contours

 Hila

 Size of lungs

 Lung markings

 Position and clarity of diaphragm

 Ribs and clavicle

 Soft tissue

 Heart size and cardiac silhouette

 Area behind the heart

 Lung apices

 First costochondral junctions

 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.

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

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.

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).

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.

Consolidation of the lung results in opacification on the CXR. This can occur due to an infective process, such as pneumonia, or pulmonary haemorrhage, when air in the lung is replaced by semi-solid material, such as an exudate or blood. The appearance of consolidation can also be due to bronchoalveolar cell cancer (adenocarcinoma in situ) (Figure 4.16).

Idiopathic pulmonary fibrosis (usual interstitial pneumonia, UIP), results in the appearance of small lungs due to volume loss, with reticulonodular shadowing, but the changes are non-specific (Figure 4.17). An HRCT is required to identify the hallmark features of sub-pleural reticulation, honeycombing, and traction bronchiectasis.

Figure 4.7 CXR showing a cavitating lesion left lower lobe.

Figure 4.8 CT thorax showing miliary tuberculosis.

Upper zone fibrosis, which can occur due to previous Mycobacterium tuberculosis infection, sarcoidosis and rarely in ankylosing spondylitis (less than 2%), can result in volume loss, resulting in tracheal deviation and elevation of the hila. The radiological changes associated with the different parenchymal lung diseases are discussed in Chapter 7.

In asthma, there may be hyperinflation of the lungs (Figure 4.18). In severe COPD, the CXR will show emphysematous lungs (Figure 4.19) and signs of hyperinflation. The CXR may appear normal in early bronchiectasis but with advanced disease the bronchi may appear dilated. A high- resolution computed tomography (HRCT) will be necessary to appreciate these changes. This is discussed in Chapter 12.

A pleural effusion (Figure 4.20) appears as an area of opacification in the lung, often with a meniscus. A small pleural effusion will result in the blunting of the costophrenic angle. A large pleural effusion will cause tracheal deviation and mediastinal shift away from the effusion. Pleural diseases are discussed in Chapter 11.

Box 4.2 CXR appearances with collapse of lobes.

 Right upper lobe collapse: elevation of the right hilum and the horizontal fissure (Figure 4.9). If collapse is due to a mass, then there will be the ‘Golden S’ sign

 Right middle lobe collapse: blurring of the right heart border (Figure 4.10). A lateral CXR will show the oblique and horizontal fissures coming together anteriorly to form a wedge (Figure 4.11)

 Right lower lobe collapse: blurring of the right hemidiaphragm and increased area of density behind the right heart shadow, with a shift of the heart to the right, and downward movement of the right hilum (Figure 4.12), A lateral CXR shows increased opacification in the posterior portion of the lower spine

 Left upper lobe collapse: the collapsed upper lobe moves forward and upwards, pulling the left lower lobe upwards and behind it (Figure 4.13). This appears as a veil within the left hemithorax without any sharp margins (Figure 4.14)

 Left lower lobe collapse: a triangular area of increased density behind the heart shadow, shift of the heart shadow to the left, blurring of the left hemidiaphragm, and increased transradiency of the left hemithorax because of compensatory expansion of the left upper lobe (Figure 4.15). This is called the sail sign

Figure 4.9 CXR showing right upper lobe collapse.

Figure 4.10 CXR (PA) showing right middle lobe collapse.

Figure 4.11 CXR (lateral) showing right middle lobe collapse.

Figure 4.12 CXR (PA) showing right lower lobe collapse.

Figure 4.13 CXR (PA) showing left upper lobe collapse.

Figure 4.14 CXR (lateral) showing left upper lobe collapse.

Figure 4.15 CXR showing left lower lobe collapse.

Figure 4.16 CXR showing right mid-zone consolidation.

CXR will also detect elevation of the diaphragm (Figure 4.21), although further imaging with CT and ultrasound will be required to determine the reason for this. CXR can show anterior and posterior mediastinal masses, although a CT will be required to show the structures in detail. The differential diagnosis, investigation, and management of mediastinal masses are discussed in Chapter 16.

Figure 4.17 CXR showing idiopathic pulmonary fibrosis.

A computed tomography scan (CT scan) is more sensitive and specific than a CXR and is required to see the structures of the thoracic cavity in detail (Figure 4.22). lodine-containing contrast is given which will show as bright white when it fills the blood vessels. A CT of the thorax and abdomen is essential for the initial staging of lung cancer and when investigating pleural diseases (Figure 4.23, Figure 4.24). Spiral images are taken contiguously, and modern CT scanners can take images of the entire lung within 3—5 seconds. Modern scanners can detect nodules 3—4 mm in size. Low-dose chest CT will expose the patient to a lower dose of radiation, which is important in those who require regular CT scans to monitor pulmonary nodules or monitor the response to treatments. The contraindications for using iodine include renal failure, allergy to iodine or to previous contrast. The CT images associated with the different conditions are depicted in each chapter discussing various lung diseases.

A CT pulmonary angiogram (CTPA) is the main investigation for suspected pulmonary embolus. Images of the pulmonary arteries are seen and can detect central and segmental pulmonary emboli with good sensitivity and specificity (Figure 4.25). The iodine-containing contrast appears as bright white within the blood vessels and pulmonary emboli will appear as dark ‘filling’ defects. CTPA has replaced conventional pulmonary angiography as the investigation of choice in most patients with suspected pulmonary embolus (PE). The guidelines recommend avoiding CTPA in pregnant and young women, if possible. The investigation of PE is discussed in Chapter 13.

Figure 4.18 CXR showing hyperinflated lungs in asthma.

Figure 4.19 CXR showing emphysematous lungs in COPD.

Figure 4.20 CXR showing a right-sided pleural effusion.

Figure 4.21 CXR showing elevation of the right hemidiaphragm.

High-resolution CT (HRCT) takes images of the parenchyma every 10 mm, and is essential in the diagnosis of parenchymal lung diseases which are discussed in Chapter 7 (Figure 4.26). When the patient is prone, better images of the lung bases posteriorly are obtained. HRCT is also useful in diagnosing bronchiectasis and emphysema (Chapter 6), lymphangitis carcinomatosis (Chapter 9) and bronchiolitis obliterans.

A positron emission tomography (PET) scan is essential in the accurate staging of lung cancer. 18 fluoro-2-deoxy-glucose, which is an analogue of glucose, is injected and is taken up by rapidly metabolising cells, including cancer cells, which release positrons which are detected by a gamma camera. Dual PET/CT scans can correlate the FDG-avid areas with the anatomy. PET is good at detecting distant metastases, especially to adrenal glands and bone.

Figure 4.22 Diagram of normal CT thorax with labels of the structures.

A PET report states the FDG-avidity of the mass, nodules and lymph nodes which is expressed as SUVmax (Figure 4.27). The sensitivity of PET for lung cancer is 80% and the specificity is 97%. A PET scan cannot be done on patients with poorly controlled diabetes mellitus and elevated blood glucose levels.

Figure 4.23 Normal CT thorax (lung windows).

Figure 4.24 Normal CT thorax (mediastinal windows).

Figure 4.25 CTPA showing bilateral filling defects in multiple pulmonary emboli.

Figure 4.26 HRCT of normal lung.

Figure 4.27 PET scan showing FDG-avid lesion in lung cancer.

A PET scan is an essential diagnostic test in the diagnosis and management of solitary pulmonary nodules and lymphadenopathy. It is not sensitive for nodules less than 8 mm. The heart and brain are metabolically active organs, so PET cannot reliably detect brain metastases. Carcinoid tumours, bronchoalveolar cell carcinoma (now called adenocarcinoma in situ), and some slowly-growing tumours may not be FDG-avid, so the results must be interpreted together with the clinical presentation and the results of all other investigations.

A bone scan is another nuclear medicine test which can detect bone metastases, osteomyelitis, and other bone disease, and is less expensive than a PET scan. Technetium-99m-methylene diphosphonate (MDP) is injected and the gamma rays emitted are detected.

A ventilation perfusion (VQ) scan is used to investigate acute and chronic pulmonary emboli (Figure 4.28). It has less sensitivity and specificity than CTPA, and many VQ scans are reported as ‘indeterminate’ but is the imaging of choice for women less than 40 years of age with suspected PE and for pregnant women. Perfusion-only scans can be done which will reduce the amount of radiation exposure. VQ scanning is also used for the investigation of chronic PE. The patient inhales a radioactively labelled inert gas (usually Xenon or technetium) to assess ventilation and then a radiolabelled contrast is injected to measure perfusion. If the patient has lung disease, such as COPD, then there will be ‘matched defects’ as areas of the lungs will be under-ventilated, and blood will be diverted away from these areas because of hypoxic vasoconstriction. If there are pulmonary emboli present, then there will be ‘unmatched defects’, with normal ventilation but no perfusion. Chapter 11 has images of VQ scans in PE. Quantitative VQ scans can also be used prior to lung resection to assess regional lung function and to estimate the amount of residual lung function.

A thoracic ultrasound is a simple, safe, noninvasive, and quick procedure which can be done at the bedside (Figure 4.29). It is particularly used for the investigation and management of pleural disease. It can show a pleural effusion, detect features of loculation and stranding, and is used to guide pleural aspiration and the insertion of a chest drain. Thoracic ultrasound can also be used to biopsy the pleura or a large lung mass. Diaphragmatic paralysis can be diagnosed by seeing the paradoxical upward movement of the diaphragm during inspiration. This, together with muscle studies, is used in the investigation of diaphragmatic palsy. Ultrasound of the liver may be indicated when liver metastases are suspected and can also be used to take a liver biopsy, which may be the way to make a histological diagnosis in some patients with poor lung function who cannot have a lung biopsy.

Magnetic resonance imaging (MRI) is a safe investigation as it does not expose the patient to radiation, but many find it difficult as it can be noisy and claustrophobic. MRI is contraindicated in those with a pacemaker or metal implants. MRI is good at giving anatomical clarity to some soft tissue structures, and to see if there is involvement of the chest wall with tumours. MRI can give useful information if thoracic surgery is being contemplated. MRI is the investigation of choice for suspected spinal cord compression.

Figure 4.28 VQ scan showing perfusion defects consistent with pulmonary emboli.

Figure 4.29 Thoracic ultrasound scan of a pleural effusion.

Lung function tests

Lung function tests, which measure airflow, lung volumes, and gas exchange, are essential in the diagnosis and management of respiratory diseases. An individual’s lung function will depend on their sex, ethnicity, age, height, and weight. The values obtained are compared to the predictive normal values which have been obtained from a large cohort of individuals and expressed as a percentage. The patient must be shown how to carry out the manoeuvre and the test should be repeated a few times to ensure reproducibility. The results of the lung function must be interpreted carefully together with information gleaned from the history, clinical examination, and radiology.

Dynamic lung volumes are easily measured in the outpatient setting and include peak expiratory flow (PEF), forced expiratory volume (FEV), forced vital capacity (FVC), and relaxed vital capacity (RVC). Patients should be advised to stop taking any inhalers for the duration of the action of the medication, for example, salbutamol for 4 hours and salmeterol for 12 hours. Patients should be asked to avoid smoking for at least 24 hours, not drink alcohol for at least 4 hours, not undertake vigorous exercise for at least 30 minutes and not consume any caffeine for at least 12 hours prior to the procedure. Other medication taken, for example, oral corticosteroids or theophylline, which will cause bronchodilation, should be noted.

The measurements should be made with the patient sitting on a high chair in non-restrictive clothing and with their dentures in, so long as these fit well. It is important to observe the patient during the manoeuvre to ensure that the technique is appropriate, that the mouthpiece is firmly held between the teeth and the lips, and that there is no air leak around the mouthpiece. The age, height, weight, and ethnicity of the patient are required to interpret the results from the available reference values. Values will be lower in the elderly.

Dynamic measurements are effort-dependent and can be manipulated by the patient. A low value will be obtained if the patient is weak, tired, or not motivated. A patient who conducts the manoeuvre by blowing against a closed glottis, or by coughing or spitting into the device, may get an artificially high reading.

Dynamic testing is contraindicated in those with haemoptysis, pneumothorax, severe hypertension, recent myocardial infarction, tachyarrhythmias, pulmonary embolus, aneurysms of thoracic or abdominal aorta, cerebral aneurysm, increased intraocular pressure, recent eye surgery or recent surgery to the abdomen or thorax.

A peak flow meter is a cheap, portable, and easy-to-use device (Figure 4.30) used to measure peak expiratory flow (PEF) in L min-1, which is a measure of resistance to air flow through the larger airways. The patient is asked to take a full inspiration and then breathe out as hard and as fast as possible into the mouthpiece, with an open glottis, to measure the maximum flow rate. The PEF is reached within the first 100 milliseconds and is sustained for approximately 100 ms. This is demonstrated in the supplementary material.

The PEF will be reduced in those with obstructive airways disease, especially conditions that result in narrowing of the medium-sized and large airways such as asthma and COPD. As COPD is largely an irreversible condition, routine PEF monitoring is not usually recommended. Diurnal PEF monitoring is an important test in the diagnosis and monitoring of asthma, which is a reversible condition. In a patient suspected of having asthma, measurement of PEF in the morning and evening should be done over several weeks to see if there is a greater than 15% variability in readings, which is approximately 50 ml/L. The patient should also be given a peak flow diary card to document the readings and to write down the symptoms experienced. The normal diurnal variation is 8%. Figure 4.31 shows diurnal PEF measurements in an individual with poorly controlled asthma. PEF monitoring is essential in the self-management of asthma, guiding the patient as to when they may require oral corticosteroids or admission to hospital (see Chapter 6). PEF monitoring may be used to diagnose occupational asthma, which is discussed in Chapter 15.

Figure 4.30 Peak flow meter.

PEF may also be reduced in diseases affecting the chest wall, such as neuromuscular diseases, kyphoscoliosis, and in conditions that affect the upper airways, such as tracheal tumour or a thyroid goitre. Therefore, PEF results cannot be interpreted on their own and spirometry testing is required.

Spirometry is cheap and easy to use in General Practice, in the outpatient department, and by the bedside. It is a measurement of the volume of air that can be exhaled during a forced expiration in one manoeuvre. The patient is asked to breathe in maximally to full inspiration and then exhale completely. The forced expiratory volume in 1 second (FEV1) and the forced vital capacity (FVC) are measured and the FEV1/FVC ratio is calculated (Table 4.1).

The FEV1 is the volume of air that can be expired with forced expiration from maximal inspiration in the first second. The vital capacity (VC) is the total volume of air exhaled from maximal inspiration. It can be a forced exhalation with maximal effort (FVC) or a relaxed exhalation (RVC), and the best value can be used. Inspiratory vital capacity is the maximal volume of air inspired from full expiration. The recommendations for dynamic testing as described above should be adhered to. Sometimes a nose clip can be used if the patient has difficulty with the manoeuvre. As with PEF measurements, the best of three readings is taken.

FEV1 and FVC are reproducible and the normal ranges for age, sex, height, and weight are well defined. As well as giving the numbers, most modern spirometers will give a print-out of the graph which should be examined as the shape of the curve will vary according to the underlying condition (Figure 4.32).

Figure 4.31 Peak flow readings showing diurnal variation.

Table 4.1 Interpretation of full lung function test.

Figure 4.32 Handheld spirometer.

In a healthy individual, the FVC and RVC are equal and should be exhaled within 4—6 seconds, with at least 70% of the air being expelled in the first second (FEVj), so that the normal FEV1/FVC ratio is 0.75-0.85 (75-85%). FEV1 and FVC peak in adults in the third decade then decline by 30 ml/year. The FEV1/FVC ratio may be less than 75% in the elderly with normal lungs.

The FEV1/FVC ratio will distinguish between obstructive and restrictive lung disease, although further tests will be required to confirm the exact diagnosis. The values determine the severity and prognosis of the condition and can be used to monitor response to treatment. In obstructive conditions, such as asthma or COPD, when there is narrowing of the large and medium-sized airways, the FEV1 (as with PEF) will be reduced. As air trapping occurs during forced expiration, FVC will be less than RVC and these patients may take up to 15 seconds to expel all the air. As FEV1 is reduced more than FVC, the ratio of FEV1/FVC is less than 0.7. Narrowing of the smaller, peripheral airways in bronchiectasis and bronchiolitis obliterans will result in a reduction in airflow over the middle-half of expiration rather than the beginning of expiration. This is reported as PEF 25—75%.

Figure 4.33 Spirometry in a normal individual and in obstructive and restrictive lung disease.

In restrictive conditions, such as interstitial lung diseases, the FVC will be reduced because of decreased lung compliance. FEV1 will also be reduced because there is less volume of air to expel, however, this is not reduced to the same extent as in an obstructive airways disease. Therefore, the FEV1/FVC ratio will be normal or increased. Figure 4.33 shows spirometry findings in the normal individual and in those with airway obstruction and restriction.

VC will also be decreased in conditions affecting the chest wall, such as kyphoscoliosis and ankylosing spondylitis, and in conditions causing diaphragmatic or inspiratory muscle weakness, such as myopathies and myasthenia gravis. Measurement of static lung volumes is required to differentiate between parenchymal diseases and chest wall diseases causing restriction.

Bronchodilator reversibility testing of peak flow and spirometry should be done to differentiate between reversible and irreversible obstruction. Most laboratories will do this only if the initial spirometry or peak flow suggest obstruction. Some 200 mcg of salbutamol is inhaled, and the measurement taken 20 minutes later. The guidelines vary slightly in their diagnostic criteria for asthma. The Association for Respiratory Technology and Physiology/British Thoracic Society (ARTP/BTS) guidelines recommend a 160 ml increase in FEV1 or 330 ml increase in VC, the European Respiratory Society (ERS) recommends a greater than 10% or 200 ml increase in predicted FEV1 and the American Thoracic Society (ATS) recommends a 12% or 200 ml increase in baseline FEV1 and FVC. A 15%, or 200 ml, increase in FEV1 or FVC suggests some reversibility and a 20% or 400 ml increase after bronchodilator is convincing evidence of reversibility. Lack of reversibility does not rule out asthma but may suggest the need for a provocation test. Exercise can induce bronchoconstriction in a hyper-responsive patient, with a 15% reduction in PEF and FEV1 post exercise. In individuals with diaphragmatic weakness, the supine VC will be 30% less than the erect VC as the contents of the abdomen push up against the diaphragm in the supine position.

The shape of the flow-volume loop can differentiate between extra-thoracic and intra-thoracic obstruction when there is narrowing of the upper airways. Flow is more effort-dependent at high lung volumes, so narrowing here will have the greatest effect on maximum expiratory flows. The volume of air inspired and expired is plotted against time. The starting point of full inspiration is to the left of the diagram, the expiratory flow appears above the horizontal line, and inspiratory flow below the line. At total lung capacity (TLC), the airways are most dilated and airway resistance is minimised, so the maximum peak expiratory flow is reached quickly after the start of the forced expiration.

Figure 4.34 Normal flow-volume loop.

Figure 4.35 Flow-volume loop in obstructive lung disease.

As expiration continues, lung volumes progressively diminish, and airway resistance increases. The maximum flow achievable declines when no further air can be exhaled, and the flow reaches zero. At this point the loop reaches the horizontal axis. The inspiratory manoeuvre is more effortdependent and less reproducible than the expiratory part, so the maximum inspiratory flow is less than the maximum expiratory flow. Figure 4.34 shows a normal flow-volume loop.

Figure 4.35 shows the flow-volume loop in obstruction; there is airflow limitation during expiration, but the inspiratory part is normal. Figure 4.36 shows the flow-volume loop in a restrictive condition where the inspiratory limb is abnormal. Figure 4.37 shows the flow-volume loop with mixed lung disease, for example, a patient with severe COPD and pulmonary fibrosis.

If there is extra-thoracic obstruction, for example, compression of the trachea by a goitre in the neck, then there is decapitation of the expiratory part of the loop with limitation of the inspiratory limb caused by tracheal narrowing during inspiration (Figure 4.38).

Figure 4.36 Flow-volume loop in restrictive lung disease.

Figure 4.37 Flow-volume loop in mixed lung disease.

If the large airway obstruction is intra-thoracic, for example, a tracheal stricture, then there will be decapitation of the expiratory limb of the loop but minimal reduction in the intra-thoracic limb (Figure 4.39).

A fixed large airway obstruction can occur when there is tracheal stenosis caused by a tracheal tumour or previous intubation. The flow-volume shows flattening of both the inspiratory and expiratory limbs (Figure 4.40).

Static (absolute) lung volumes are required to make an accurate diagnosis, especially in those who have restriction on spirometry (Figure 4.41). The total lung capacity (TLC) is the total volume of air in the lungs after full inspiration, the functional residual capacity (FRC) is the volume of air left in the lungs at the end of normal tidal expiration and the residual volume (RV) is the amount of air left in the lungs after maximum expiration. The vital capacity (VC) is the volume of air expelled by full expiration after full inspiration. The tidal volume (TV) is the volume of air that enters and leaves the lungs during normal breathing.

Static lung volumes are measured in a Lung Function Laboratory using the helium dilution method or the whole-body plethysmography method. In the helium dilution technique, air with a known concentration of helium is breathed through a closed circuit and the volume of gas in the lungs is calculated from a measure of the dilution of the helium. Helium is an inert gas which is not absorbed or metabolised. The gas dilution method only measures gas in communication with the airways and underestimates TLC in patients with severe airway obstruction because of poorly ventilating bullae or those with cystic lung disease.

Figure 4.38 Flow-volume loop in variable extra-thoracic upper airway obstruction.

Figure 4.39 Flow-volume loop in variable intra-thoracic obstruction.

Figure 4.40 Flow-volume loop in fixed large airway obstruction.

Figure 4.41 Static lung volumes: Total Lung Capacity (TLC), Expiratory Reserve Volume (ERV), Residual Volume (RV), Vital Capacity (VC), Functional Residual Capacity (FRC), Inspiratory Capacity (IC), Tidal Volume (TV).

The whole-body plethysmography test uses a large airtight body box that allows the simultaneous determination of pressure-volume relationship in the thorax of a patient placed inside this box. When the plethysmograph is sealed, changes in lung volume are reflected by a change in pressure within the plethysmograph. Plethysmography tends to overestimate TLC because it measures all intra-thoracic gas, including gas in bullae, cysts, stomach, and oesophagus. The values obtained by either method are compared with the predicted values of individuals of the same age, sex, ethnicity, height, and weight and given as a percentage predicted.

TLC will be reduced in any intrapulmonary or extra-pulmonary restrictive disorder and increased in conditions that result in air-trapping. FRC will also be increased in conditions that cause airway obstruction, such as COPD. RV and FRC can distinguish between different types of restrictive conditions. Both RV and FRC will be decreased in parenchymal lung diseases whereas RV will be reduced but FRC will be normal in conditions causing respiratory muscle weakness and obesity.

A single-breath method is used to measure the transfer coefficient factor for carbon monoxide (TLCO), also called the diffusing capacity, which is an estimate of the amount of CO which diffuses across the alveolar-capillary membrane. A very low concentration of CO is used as a surrogate for O2.

To measure TLCO we need to know the amount of CO transferred across/minute and the pressure gradient across the alveolar membrane. TLCO is a sensitive but not specific measurement.

The patient is asked to breathe in a mixture of helium and CO, then hold their breath for 10 seconds and then exhale completely. The volume of gas equivalent to the dead space (approximately 1500 ml) is discarded. The remaining sample is analysed for concentrations of helium and CO. Helium is not absorbed or metabolised as it is an inert gas. Therefore, the change in concentration of helium between the inspired and expired samples is the amount of gas dilution and is used to estimate the alveolar gas volume (VA). The expired concentration of CO is lower than the inspired level as some of the CO is absorbed into the bloodstream. The rate of uptake of CO is calculated as the uptake/minute/unit of partial pressure of CO (mmol min-1 kPa-1).

The transfer coefficient (KCO) is the transfer factor per unit alveolar volume (VA) and is also measured using the single breath-hold technique. TLCO = KCO/VA and is corrected for haemoglobin. KCO measures the transfer of CO in the alveoli that are ventilated. The non-ventilated alveoli are not measured as they do not contribute to the alveolar gas volume (VA).

TLCO is reduced by conditions which result in ventilation/perfusion mismatch. This includes conditions which impede blood flow, such as a pulmonary embolus, conditions that reduce the alveolar surface area, for example, bullous emphysema, and diseases that impede transport of oxygen across the capillary membrane as occurs in parenchymal lung diseases. KCO too will be decreased with these intrinsic lung diseases.

TLCO is also reduced by conditions which result in a reduction in the volume of healthy lung available to participate in gas transfer, for example, respiratory muscle weakness causing restriction, chest wall deformity, such as kyphoscoliosis, obesity and after a pneumonectomy. Unlike TLCO, KCO is not diminished by extrathoracic restrictive conditions and may be elevated as KCO only measures the transfer of CO in ventilated alveoli which have more than their normal share of blood as blood is diverted away from the non-ventilated alveoli. The greater blood volume increases CO absorption and gas transfer.

TLCO increases when the pulmonary capillary blood volume increases, for example, with a high cardiac output state, with polycythaemia, and pulmonary haemorrhage.

Respiratory muscle function tests are used to measure weakness of the respiratory muscles which can cause a restrictive ventilatory defect with decreased TLC and VC. In diaphragmatic palsy, the pressure of the abdominal contents pushing up against the weak diaphragm results in a 30% fall in VC when supine compared to the erect position. Two small balloon-tipped catheters, one measuring the oesophageal pressure and the other the gastric pressure, are inserted to measure the differences in pressure. Generalised respiratory muscle function may be assessed by measuring mouth pressures. Maximum inspiratory mouth pressure, Pi max, is measured during maximum inspiratory effort from a residual volume against an obstructed airway using a mouthpiece and transducer device. Maximum expiratory mouth pressure, Pe max, is measured during maximum expiratory effort from TLC.

Methacholine provocation testing can be used to measure the degree of airway responsiveness and is recommended in those who are suspected of having asthma but who have normal spirometry with no significant bronchodilator response. It is particularly useful in those with cough-variant asthma. The patient should be instructed to stop oral corticosteroids, theophylline, and inhaled medications for a few days before the procedure is undertaken. A baseline spirometry is done, then a small dose of methacholine is inhaled, and spirometry repeated. The dose of methacholine should be gradually increased and serial spirometry carried out. The concentration of methacholine required to provoke a 20% fall in FEV1 is calculated. If this is less than 32 mg, then asthma is confirmed. This investigation is usually done in Respiratory Units and closely supervised, with bronchodilators available, as there is a risk of severe bronchoconstriction. Histamine can be used instead of methacholine.

Measurement of fractional exhaled nitric oxide (FeNO), a marker of airway inflammation, is recommended by NICE in the diagnosis of asthma. It is a quick, simple, and non-invasive test, but the results must be used in conjunction with the results of other investigations. A negative test does not exclude asthma.

Exercise testing

Exercise (walking) tests are used to determine the severity, response to treatment, and prognosis in patients with chronic respiratory diseases, including COPD, pulmonary hypertension, diffuse parenchymal lung diseases, and in chronic heart failure. The procedure must be standardised, with clear instructions to each patient.

Exercise tests are an important part of the assessment of functional status and required in those who are being considered for lung transplantation, heart and lung transplantation, or lung volume reduction surgery. These measurements are often the primary end-point in trials looking at the efficacy of treatments in these conditions. Exercise testing is contraindicated in those who have had a recent myocardial infarction, those with severe angina, and those with uncontrolled hypertension.

The six-minute walk test (SMWT) is easy to do, safe and well tolerated, even in patients who have limited exercise tolerance. The patient is asked to walk along a straight line on a hard surface, on his/her own and the distance walked in six minutes is measured. The oxygen saturation and extent of breathlessness should be determined. The SMWT correlates well with pulmonary function tests, quality of life measures, and mortality. This is demonstrated in the supplementary material.

The shuttle walk test (SWT) requires the patient to walk back and forth between two markers set 10 metres apart in response to a pre-set timer. The timer beeps to indicate when the patient should have reached the marker. The interval between beeps will gradually decrease until the patient is unable to keep up. Both the SWT and the SMWT will improve with inhaled therapy for COPD and with pulmonary rehabilitation. Oxygen saturation should be measured at rest and during the SMWT and the SWT. The oxygen saturation correlates with disease severity and can be used to monitor the progression of the disease and any improvement with treatment.

Cardiopulmonary exercise testing is an important investigation in the assessment of patients with breathlessness, and is used to determine disease severity. The ventilatory reserve can be measured by examining the relationship between peak exercise ventilation (VE) and the maximal voluntary ventilation (MVV). It is not within the scope of this textbook to discuss this in any further detail.

Sleep studies

Several investigations are available for patients presenting with sleep disordered breathing. The simplest is an overnight oximetry when an oximeter probe is placed on the patient’s finger overnight. A drop of 4% or more in the oxygen saturation is abnormal and the number of these desaturations every hour can be measured. More than 15 desaturations per hour is diagnostic of obstructive sleep apnoea, although the exact criteria vary from laboratory to laboratory.

Polysomnography is more sensitive and specific and involves overnight measurement of oxygen saturation, thoracic and abdominal movement, snoring, pulse, and blood pressure. This can be done in the patient’s home using a portable device. Full polysomnography is indicated if a more complex sleep disorder, such as restless leg or central sleep apnoea, is suspected. This is conducted in a sleep laboratory and involves measuring the stages of sleep using an electroencephalograph (EEG). During normal sleep, 25% of the activity will be rapid eye movement (REM) sleep and the rest is non-rapid eye movement sleep (NREM). Muscle activity and eye movements are measured using an electromyogram (EMG) and electro-oculogram (EOG) and are important in the diagnosis of restless leg syndrome and other sleep-related disorders which are discussed in Chapter 14.

The multiple sleep latency test (MSLT) is used to determine the degree of daytime somnolence and is important in the diagnosis and management of narcolepsy and idiopathic hypersomnia (IH). The patient is placed in a dark room during daytime and asked to lie down to sleep. A normal individual will take 10—20 minutes to fall asleep, whereas an individual with narcolepsy or IH will fall asleep in less than 8 minutes. Once the individual falls asleep, he/she should we woken up after 15 minutes. The patient will have five scheduled naps during the day, each separated by two hours.

Cardiology investigations

An electrocardiogram (ECG) is an important basic investigation in patients presenting with chest pain, breathlessness, and syncope. Patients with these symptoms are often referred to the respiratory clinic. Cardiac causes, including ischaemic heart disease, hypertensive disease, valvular heart disease, and arrhythmias must be excluded. The ECG will be abnormal in those presenting with pulmonary embolus, with the commonest finding being sinus tachycardia. ECG features of right heart strain, right bundle branch block, right axis deviation and S1Q3T3 are also indicative of pulmonary embolus, which is discussed in Chapter 11. The ECG will be abnormal in patients with pulmonary hypertension and cor pulmonale.

An echocardiogram measures the structure and function of the left and right side of the heart, the structure of the pulmonary arteries, the structure and function of the valves, and the pericardium. Patients with pulmonary hypertension will have a raised pulmonary artery pressure (PAP), estimated by measuring the tricuspid regurgitant wave, and right ventricular hypertrophy. Pulmonary hypertension is discussed in Chapter 11.

Invasive investigations

A nose and throat examination (nasendoscopy) is carried out for the investigation of a chronic cough. It is safe and easy to do, has little morbidity and can be done without sedation using local anaesthetic. This can be used to directly visualise the nasal passages to look for evidence of infection, crusting, abnormal nasal pathology, and nasal polyps. The oropharynx can be examined for evidence of candida, acid reflux and cobblestoning. Nasen- doscopy can also be used to look at the movement of the vocal cords and diagnose vocal cord palsy and vocal cord dysfunction,

A bronchoscopy is an invasive test that is essential in the diagnosis, treatment and management of lung malignancies, infections, and interstitial lung diseases. Flexible fibre-optic bronchoscopy is done as a day case. It is safe in most patients, with a low complication rate. It is conducted under sedation (intravenous midazolam) and local anaesthetic (lignocaine), with careful monitoring of the pulse rate and oxygen saturation. It is used to examine the appearances of the nasal passages, oropharynx, epiglottis, and vocal cords. After instillation of adequate lignocaine to the vocal cords, the trachea, carina and right and left bronchial trees can be directly visualised to the fourth and fifth divisions of the endobronchial tree. Vocal cord palsy, tumours of the vocal cord, tracheal tumours, tracheomalacia, and endobronchial tumours can be seen at bronchoscopy.

Biopsies and brushings can be taken from the area of abnormality. Significant bleeding can occur when biopsies are taken, especially from abnormal tissue, so the clotting and platelet count should be checked prior to taking biopsies. The position of the tumour can give information about the operability of the tumour. Bronchoscopy is also indicated for the removal of a foreign body, more common in small children who may inhale it. Samples of bronchoalveolar lavage (BAL) taken at bronchoscopy are commonly used in the investigation of lung cancer and lower respiratory tract infections. Cytology from lavage and brushings, and histology from endobronchial biopsies are used to diagnose lung cancer, including bronchoalveolar cell carcinoma (adenocarcinoma in situ) and carcinoid tumour of the lung. Microbiological analysis is used to diagnose respiratory tract infections, including MTB, and pneumocystis jerovici, particularly when sputum is not available. The differential cell count in the lavage fluid can be helpful in the diagnosis of several respiratory diseases, including asthma, COPD, sarcoidosis, and interstitial lung diseases. Transbronchial biopsy is used in the diagnosis of diffuse parenchymal lung disease, including sarcoidosis, and is discussed in Chapter 7.

Therapeutic suctioning at bronchoscopy clears increased volumes of mucopurulent or purulent secretions and allows better aeration of the lungs. Transbronchial lymph node aspiration (TBNA) and endobronchial ultrasound-guided biopsy (EBUS) of lymph nodes are minimally invasive tests which are now widely available to obtain biopsies from enlarged hilar, mediastinal, and subcarinal lymph nodes which may be enlarged due to malignancy (including lymphoma), MTB, or sarcoidosis.

When there is significant narrowing of the bronchus with tumour or granulation tissue, laser or cryotherapy can be used to reduce the narrowing, at least temporarily. This is a palliative procedure in patients with lung cancer and can improve breathlessness. In some cases, an endobronchial stent can be inserted to improve ventilation of the airways. Endobronchial radiotherapy can also be used. A rigid bronchoscopy conducted under general anaesthetic may be required for more complicated procedures, especially if there is a significant risk of bleeding or airway compromise. Thoracic surgical back-up should be available.

Peripheral lung nodules and masses can be sampled by fine needle aspiration (FNA) under CT or ultrasound guidance (Figure 4.42). Lymph nodes outside the thoracic cavity, for example, in the supraclavicular fossa, can also be sampled, either by FNA or Trucut biopsy, which give larger samples for histological analysis. In the diagnosis of lung cancer, it may be easier to biopsy other areas of abnormality, such as liver, bone, or subcutaneous nodules.

If pleural disease is suspected, then aspiration of pleural fluid under thoracic ultrasound is undertaken and fluid sent for cytology, microbiology, and biochemistry. This is discussed in greater detail in Chapter 10. Chest drain will be required for drainage of large pleural effusions and a chemical pleurodesis can be carried out in those with recurrent malignant pleural effusions who are not fit for a surgical pleurodesis. A pleural biopsy can also be conducted under CT guidance when a pleural malignancy is suspected.

Figure 4.42 CT-guided FNA of lung mass with needle in pulmonary lesion.

Medical thoracoscopy can be done under intravenous sedation and the pleural space can be examined for evidence of malignancy, biopsies taken, and pleurodesis carried out. For those with pleural disease, a video-assisted thoracoscopic surgery (VATS) is often the investigation of choice but will require a general anaesthetic and will be carried out by the thoracic surgeon. The pleural cavity can be directly visualised, biopsies taken, and surgical pleurodesis carried out. The VATS procedure can be used to take lung biopsies, perform wedge resection, and lobectomy. A full thoracotomy will be needed for a pneumonectomy. The thoracic surgeon can also sample mediastinal lymph nodes at mediastinoscopy.

A right heart catheter is used to measure the right heart pressure in patients with pulmonary hypertension and to monitor the effect of the treatments for pulmonary hypertension. Other invasive procedures include the insertion of a stent for superior vena cava obstruction, emergency cricothyroidectomy for upper airway obstruction, tracheostomy for those requiring long term invasive ventilation, and surgical embolectomy for patients with massive pulmonary embolus who do not respond to thrombolysis or in whom thrombolysis is contraindicated.

Miscellaneous investigations

A variety of genetic tests, including prenatal testing, are available for the diagnosis of cystic fibrosis, primary ciliary dyskinesia, and a-1 antitrypsin deficiency. HLA B27 testing may be positive in patients with ankylosing spondylitis.

 A variety of investigations are available to aid the diagnosis of patients presenting with respiratory symptoms and signs.

 Many of the blood tests are non-specific but can rule out other causes of the symptoms; for example, anaemia can contribute to breathlessness.

 Radiological investigations are essential in the diagnosis of respiratory diseases.

 The CXR is the commonest radiological investigation worldwide and can be helpful in many conditions, including pneumonia and lung cancer.

 CT thorax gives information about the main structures in the thorax and mediastinum, including masses and lymph nodes, and is an essential investigation in the diagnosis of lung cancer, pleural disease, and mediastinal tumours. A CT- guided biopsy can be done to take samples from tumours and the pleura.

 The CTPA will detect acute pulmonary emboli by visualising the pulmonary arteries up to the segmental arteries.

 The HRCT is necessary in diagnosing parenchymal lung diseases, including pulmonary fibrosis and sarcoidosis.

 The VQ scan is less specific and sensitive than a CTPA for diagnosing pulmonary emboli but is indicated in young women

and pregnant women as it exposes them to less radiation. It is also the investigation of choice if chronic pulmonary emboli are suspected.

 The PET scan uses 18fluoro-deoxyglu- cose, a glucose analogue, which is taken up by rapidly metabolising cells. It is essential in the staging of lung cancers and other malignancies. It can detect local and distant metastases but is not good at detecting brain metastases.

 Thoracic ultrasound is a non-invasive investigation used in the investigation of pleural disease and to guide the insertion of a needle for pleural aspiration, pleural biopsy and for chest drain insertion.

 An MRI scan of the thorax is important in the diagnosis of mediastinal masses and chest wall disease, including invasion by tumour, spinal cord compression and brain metastases.

 Lung function tests are essential in the diagnosis of many respiratory diseases, in determining the prognosis and in monitoring progression and response to treatment. This includes peak expiratory flow measurement, spirometry and measurement of static lung volumes; total lung capacity, residual volume, and functional residual capacity.

 Measurements of transfer coefficient and the transfer factor are essential in approximating the diffusion of oxygen through the capillary membrane from the alveolus and can differentiate between parenchymal and extra-thoracic causes of a restrictive lung disease.

 Sleep studies are used to diagnose sleep-related disorders, which include obstructive sleep apnoea, central sleep apnoea, periodic limb disorders, narcolepsy, and idiopathic hypersomnia. This includes overnight oximetry, overnight sleep study, polysomnography and multiple sleep latency test.

 Exercise testing is important in assessing the functional status of a patient with respiratory disease. This includes the six-minute walk test and the shuttle test. It gives prognostic information, is used to monitor response to treatment and is the primary end-point in many trials in respiratory disease.

 An ECG is important in diagnosing cardiac conditions, including ischaemic heart disease, arrhythmias, and right heart strain which can occur after a pulmonary embolus and with pulmonary hypertension.

 An echocardiogram is important in the diagnosis and management of pulmonary hypertension and in the assessment of the severity of a pulmonary embolus.

 Bronchoscopy is an important investigation in the diagnosis of lung cancer, respiratory infections and interstitial lung diseases. Histology can be taken at biopsy, cytology by bronchial brushings and bronchoalveolar lavage. Samples from lavage can also be sent for microbiological analysis and for differential cell count.

 Pleural procedures include simple ultrasound-guided pleural aspiration, pleural drainage, medical thoracoscopy, and video-assisted thoracoscopic procedures used to visualise the pleura, take biopsies, and to carry out pleurodesis.

MULTIPLE CHOICE QUESTIONS

4.1 Which of the following is NOT associated with lung cancer?

A Hypercalcaemia

B Hyponatraemia

C Raised CRP

D Raised d-dimer

E Raised IgE

Answer: E

All the above can be found with lung cancer apart from IgE which will be raised in allergic conditions, including asthma and ABPA.

4.2 Which of the following investigations is most likely to yield a diagnosis in a patient presenting with a malignant pleural effusion?

A Bronchoalveolar lavage

B Pleural fluid cytology

C Transbronchial biopsy

D Tumour markers E VATS pleural biopsy

Answer: E

A VATS pleural biopsy allows for direct visualisation of the pleura and biopsies can be taken for histology. Pleural fluid cytology may be diagnostic, but not in most cases. Histology is always preferable to cytology. The other investigations are not indicated for a pleural effusion, although bronchoalveolar lavage and transbronchial biopsy may be helpful if there is an endobronchial lesion. Tumour markers are not helpful in making the diagnosis.

4.3 What are the CXR features of right upper lobe collapse?

A Blurring of the right heart border

B Blurring of the right hemidiaphragm

C Depression of the right hilum

D Elevation of the horizontal fissure

E Elevation of the right hemidiaphragm

Answer: D

When the right upper lobe collapses, the rest of the right lung is shifted upwards. This means that the horizontal fissure, which divides the right upper and middle lobes, and the right hilum are elevated. Blurring of the right heart border is found with right middle lobe collapse and blurring of the right hemidiaphragm is seen with right lower lobe collapse.

4.4 Which of the following conditions is NOT associated with a cavitating mass on CXR?

A Bronchoalveolar cell carcinoma (adenocarcinoma in situ)

B Lung abscess

C Mycobacterium tuberculosis infection

D Squamous cell carcinoma

E Staphylococcus aureus pneumonia

Answer: A

Bronchoalveolar cell carcinoma looks consolidative, with patchy, white shadowing. All the other conditions listed are in the differential diagnosis for a cavitating lesion. Other conditions that result in a cavitating mass include vasculitic conditions and pulmonary infarct.

4.5 Which of the following statements about a PET scan is true?

A Contraindicated in a patient with chronic renal failure

B Contraindicated in a patient who is allergic to seafood

C Excellent at detecting brain metastases

D Sensitivity for lung cancer is 99%

E Specificity for lung cancer is 97%

Answer: E

Positron emission tomography (PET) uses 18fluoro-deoxy glucose and not iodine-containing contrast. This radioactive glucose analogue is taken up by rapidly metabolising cells, including cancer cells. Slow-growing tumours, such as carcinoid or bronchoalveolar cell tumour (adenocarcinoma in situ) may not be PET-avid. PET cannot reliably detect metastases in metabolically active organs like the brain and heart. The sensitivity of PET in detecting lung cancer is 80% and the specificity is 97%.

4.6 Which of the following statements about ventilation/perfusion (VQ) scanning is true?

A Many VQ scans are reported as indeterminate

B Matched defects suggest chronic pulmonary emboli

C It is more sensitive at detecting acute pulmonary emboli than CTPA

D It should be avoided in pregnant women

E It is the investigation of choice in COPD

Answer: A

Many VQ scans are reported as indeterminate so that further imaging with CTPA is often required, as it is less sensitive than CTPA. Matched defects are found when there is reduced ventilation and therefore perfusion, for example, in COPD. VQ scanning is therefore not indicated in chronic lung diseases. A VQ scan is the investigation of choice for a pregnant woman suspected of having a pulmonary embolus as this exposes her and the foetus to less radiation than a CTPA. A perfusion scan alone can be considered in this group.

4.7 Which of the following combination of findings is consistent with emphysema?

Answer: B.

Emphysema is an obstructive airways disease and therefore FEV1 will be reduced. As there is air-trapping and there will be bullae, the total lung capacity will be increased. The transfer coefficient (TLCO) will be reduced as the alveolar-capillary interface is destroyed.

4.8 The following combination of findings in lung function testing suggest which of these conditions? ↓FVC, normal FEV1/FVC ratio, ↓TLCO and ↑KCO.

A Asthma

B Bronchiectasis

C COPD

D Obesity

E Pulmonary fibrosis

Answer: D

The decreased FVC rules out asthma, bronchiectasis, and COPD which are obstructive conditions. In any parenchymal lung disease, the FEV1/FVC ratio may be normal or increased, but the TLCO and KCO will be reduced. In extrathoracic conditions, such as obesity, neuromuscular diseases and musculoskeletal diseases the TLCO will be reduced but the KCO will be increased.

4.9 Which of the following investigations is most likely to confirm a diagnosis of diaphragmatic palsy?

A Arterial blood gas measurement

B CT thorax and abdomen

C Lateral CXR

D Lying and standing vital capacity

E Shuttle walk

Answer: D

Individuals with unilateral diaphragmatic palsy may be relatively asymptomatic except when supine or underwater, for example, swimming or in a bath, because of the pressure of the abdominal contents pushing up against the weak diaphragm. ABG will be normal. The CXR and CT thorax will show elevation of the hemidiaphragm but this, by itself, is not diagnostic of diaphragmatic palsy. A reduction by 20% in the VC when supine suggests diaphragmatic palsy. Diaphragmatic muscle studies will then confirm this.

4.10 A multiple sleep latency test (MLST) is used to diagnose which condition?

A Central sleep apnoea

B Insomnia

C Narcolepsy

D Obstructive sleep apnoea

E Periodic limb movement

Answer: C

MSLT, which measures how quickly someone falls asleep during the daytime, is used to diagnose narcolepsy and idiopathic hypersomnia. A sleep study is required to diagnose OSA and a full polysomnography with EEG and EMG monitoring is required to diagnose central sleep apnoea and periodic limb movement.

FURTHER READING

Albert, R.K., Spiro, S.G., and Jett, J.R. (1999). Comprehensive Respiratory Medicine. London: Mosby.

American Thoracic Society (ATS), Crapo, R.O., Casaburi, R. et al. (2002). ATS statement: guidelines for the six-minute walk test. American Journal of Respiratory and Critical Care Medicine 166 (1): 111-117.

American Thoracic Society and American College of Chest Physicians (2003). ATS/ACCP statement on cardiopulmonary exercise testing. American Journal of Respiratory and Critical Care Medicine 167 (2): 211-277.

British Thoracic Society and the Association of Respiratory Technicians and Physiologists (1994). Guidelines for the measurement of respiratory function: recommendations of the British Thoracic Society and the Association of Respiratory Technicians and Physiologists. Respiratory Medicine 88 (3): 165-194.

Brown, C.D. and Wise, R.A. (2007). Field tests of exercise in COPD: the six-minute walk test and the shuttle walk test. COPD: Journal of Chronic Obstructive Pulmonary Disease 4 (3): 217-223.

Gibson, G.J. (2009). Clinical Tests of Respiratory Function, 3e. London: Hodder Arnold.

Hansell, D. (2003). Thoracic imaging. In: Respiratory Medicine (ed. G. Gibson, D. Geddes, U. Costabel, et al.), 316-351. London: W. B. Saunders.

Hansell, D.M. and Armstrong, P (2005). Imaging of the Diseases of the Chest, 4e. Edinburgh: Elsevier Mosby.

Kinnear, WJ.M. (1997). Lung Function Tests: A Guide to their Interpretation. Nottingham: Nottingham University Press.

Lima, D.M., Colares, J.K.B., and Da Fonseca, B.A.L. (2003). Combined use of the polymerase chain reaction and detection of adenosine deaminase activity on pleural fluid improves the rate of diagnosis of pleural tuberculosis. Chest 124 (3): 909-914.

Newall, C., Evans, A., Lloyd, J. et al. (2000). ARTP Spirometry Handbook. Birmingham: Association for Respiratory Technology and Physiology.


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