Malignant nodules Percentage Benig Percentage nodules 25% Adenocarcinoma 47% Healed/ non-speci \201 c granulomas Squamous cell carcinoma 22% Solitary metastasis Undifferentiated 8% Granulomatous infections 15% NSCLC 7% Hamartomas 5% Etiology There are several possible causes for a SPN (Table 3.6.1), but > 95% are neoplasms (usually primary), granulomas (usually infection) or hamartoma (Table 3.6.2). SCLC 4% Bronchioloalveolar cell 4% Table 3.6.1 Causes of solitary pulmonary nodules CT densitometry measures the attenuation of a lesion and aids detection of calci \201 cati on. Enhancement with IV contrast also suggests malignancy. However, the sensitivity and spe ci \201 city of these measurements are low and combi- nation with other clinical and radio logical features in- creases their usefulness. Low-dose techniques should be used to reduce the dose of radiation if multiple follow-up CT scans are required. Neoplastic (malignant or benign) Bronchogenic carcinoma Single metastasis Lymphoma Carcinoi d Connective tissue & neural tumors \200\223 \201 broma, neuro \201 broma, blastoma, sa rcoma Hamartoma Lipoma Nodule characteristics Size: Table 3.6.3 shows the relationship between size and risk of ma lignancy. Lesions >3cm in diameter are very likely to be malignant, but other possible caus es include lung ab- scess, Wegener \200\231s granulomatosis, round pneumonia, rounded atele ctasis, and hydatid cyst. Nodules <8mm are too small to biopsy or assess with positron emis sion tomography (PET) so the most sensible option is follow-up CT. Shape: generally unhelpf ul but, a very irregular edge, co- rona radiata (spiculation), lobulation, or notching sugg est bronchogenic carcinoma. A well-de \201 ned, smooth edge suggests a benign lesion or me tastasis. In \202 ammatory (infectious) Granuloma \200\223 TB, histoplasma, coccidioidomycosis, bla stomycosis, Cryptococcus, Nocardia Lung abscess Round pneumonia Hydatid cyst In \202 ammatory (non-infectious) Rheumatoid arthritis Wegener \200\231s granulomatosis Sa rcoidosis Lipoid pneumonia Congenital Arteriovenous malformation Sequestration Lung cyst Table 3.6.3 Method of detection, size of nodule and risk of malignancy Method of detection Size (mm) Approximate risk of Others Pulmonary infarct Round atelectasis Mucoid impaction malignancy CT only \211 4 <1% CT, Rarely CXR >4 \200\2238 6% CXR or CT >8 \200\22330 50% Initial detection of a SPN: CXR and CT Chest radiography: provides information on size, sha pe, cavitation, growth rate, and calci \201 cation. These features can help suggest whethe r the lesion is benign or malignant. However, none are speci \201 c (see below). CT has ma ny advantages over CXR e.g. better resolution and detection of small nodules. Regions that are dif \201 cult to Attenuation: nodules may be solid, non-solid (ground glass; underlying lung parenchyma pres erved and visible through nodule) part solid (mixed solid and ground glass). Table 3.6.4 sh ows how the risk and growth rate of malig- nancies vary between these types of nodule. CHAPTER 3.6 Solitary pulmonary nodule 47 Rate of growth: serial CXR or CT can assess growth (dou- bling time; Td i.e. doubling of no dule volume). A 26% in- crease in diameter (e.g. 11mm to 14mm) on CXR re \202 ects a doubl ing of volume as nodules are seen in 2-D rather than 3-D and the volume of a sphere is 4/3i r3. However, a 3mm change is dif \201 cult to detect using CXR. The Td of bronchogenic ca rcinoma is generally 1 \200\22318 months (mean 4 \200\2238). Outside this range bronchogeni c car- cinoma is unlikely but not impossible; <1 month suggests infections; >18 suggests be nign processes (e.g. granuloma, hamartoma, carcinoid, rounded atelectasis). If there is no change over 2 years, the SPN is probably benign. Further follow-up (up to 5 years), may be indicated particularly for non-solid nodules as indolent malignancies with Td >730 days may be missed (see Table 3.6.4). Most studies have focused on investigation and very few outcome studies have been performed . The suggestions in this review are therefore based on evidence that is graded 1B-2C at be st. The mortality associated with lung cancer is generally high (5-year survival rate 14%), but early lung cancer, (stage 1A; T1N0M0; primary tumor <3cm), may have a 5-year survival rate of 70-80%. Metastastectomy also offers the potential of cure to some patients with tre ated extra-pulmonary malignancy. Thus, the patient with cancer who presents with a SPN coul d be cured. It is impossible to ignore the emotional and medicolegal implications of missin g a potentially curable cancer. Most recommendations (and current practice) at least partly re \202 ect this anxiety. This must be balanced against the substantial radiation exposur e this group of patients may receive and which may itself induce malignancy. Table 3.6.4 Nodule characteristics, doubling time and risk of malignancy Further investigations Lab studies: the role of lab studies is limited. Anemia or elevated in \202 ammatory markers may suggest malignancy or infection. Deranged liver function test s or bone pro \201 le may suggest metastases. Histoplasma or coccidioidomyco- sis serology may identify infections with these fungi. A gamma interferon blood test (e.g. Elispot) can be used to detect tuberculosis. Sputum cytology: is generally only indicated for investiga - tion of patients with central nodules who are unable to tolerate or unwilling to undergo other invasive tests. PET: the metabolic rate and glucose uptake of malignant nodules is gr eater than normal lung. Thus enhancement on 18-F-2 \202 uorodeoxyglucose (FDG) PET makes it likely to be malignant. The sensitivity and speci \201 city are >90% and me- diastinal metastases can be detected, improving the staging of non-invasive lung cancer. Furthermore, the yield from biopsy may be increased if the metabolically active regions of nodules are sampled. However, false-positives occur in infectious or in \202 amma- tory nodules which are metabolically active. Tumors with low metabolic rates (e.g. carcinoid and bronchoalveol ar carcinoma) may be dif \201 cult to distinguish from background activity. Furthermore, F DG-PET is less sensitive for nod- ules <20mm in diameter and may miss lesions <10mm. Single -photon emission computed tomography (SPECT): cheaper than PET but the sensitivity, speci \201 city and diag- nostic accuracy (89%, 67%, and 81%, respectively) are simi- lar. It is performed using a radiolabeled somatostatin-type receptor binder, technetium Tc P829. SPECT has not been assessed in large studies; in a smaller series, the sensitivity fell signi \201 cantly for nodules <20mm. Bronchoscopy and transbronchial needle aspiration (TBNA): ma y be helpful if the SPN is endobronchial, near a large airway or mediastinal nodes need to be sampled. Because the diagnostic yield from bronchoscopy is gener- ally <20% if the SPN i s <2cm, bronchoscopy has a limited role in the investigation of SPN. Transthoracic aspirati on biopsy (TTAB): the accuracy is high (90 \200\22395%) when the SPN is \211 2cm, but is l ess (60 \200\22380%) in lesions <2cm. Sensitivity for speci \201 c benign diagnosis is low er (11 \200\22368%); so most specimens are non-diagnostic. Complications include pneumothor ax which occurs in up to 30% (of these 5% require a chest drain) and haemoptysis which occu rs in 5 \200\22310% (usually minor and resolves sponta- neously). HRCT characteristics Risk Mean Td of malignancy (days) Non-solid (ground glass) 34% 813 Partly solid (<15mm) 40 \200\22350% 457 Solid (<10mm) 15% 149 Calci \201 cation: often indicates that the SPN is benign. CT is the most sensitive techni que for detecting calci \201 cation. Patterns of calci \201 cation usually seen in benign lesions are diffuse, central, laminar, concentric and popcorn. Stippled or eccentric patte rns are associated with malignancy. Fat: within a SPN can be seen with CT and suggests ham- artoma or lipoma but metastases from a liposarcoma or renal cell cancer may rarely contain fat. Other features: invasion of adjacent bone = bronchogenic carcinoma. Cavitation with t hin (<1mm), smooth walls sug- gests lung abscess or a benign lesion, but thick walls may be present in benign or malignant lesions. False positives/negatives: up to half of the nodul es seen on CXR are false-positive \201 ndings; the presence of the nodule not seen on sub sequent CT. SPN mimics include nipple shadows, summation shadows, soft tissue tumors, bone shadows, pleural plaques, pseudotumours and round atelectases. Differential diagnosis Whether to biopsy, resect, or observe a nodule should be decided wit hin 1 month of presentation. Patients with a SPN are usually asymptomatic but symptoms, sig ns and baseline imaging studies (CXR and CT) can be used to determine differential diagnose s and perform a risk assess- ment for malignancy. The SPN should be classi \201 ed as like ly to be benign, malig- nant, or indeterminate. Bayesian analysis which uses likeli- hood r atios of malignancy for various clinical and imaging factors may guide risk assessment. The ratios are combined to produce a probability of malignancy (PCa). Management of clearly be nign or malignant nodules is straightforward. The management of the indeterminate nodule, h owever, is more dif \201 cult. The aim is to resect (cure) early-stage malignancy whilst a voiding the morbidity and mortality of surgery for benign nodules. R RAJENDRAM 48 Further reading Diagnosis and treatment of lung cancer. National Collaborating Center for A cute Care. London 2005. Available from www. rcseng.ac.uk. As samples may be taken from normal tissue adjacent to a SPN the negative predictive value is low. Further manage- ment depends on PCa and patient-related factors such as operative r isk. Thoracotomy should be considered if PCa is high. Thoracoscopy or thoracotomy: thoracot omy should be considered in patients with an indeterminate nodule and a high PCa, if lung f unction is adequate. Peripheral nodules can also be removed using VATS. If frozen sections con \201 rm malignancy complete resection can be performed by open thoracotomy. If benign, thoracotomy and lobectomy can be avoided. Gould MK, Fletcher J, Iannettoni MD, et al. Evaluation of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence based clinical practice guidelines. Chest 2007; 132: 108 \200\223130. Miller JC, Shepard JA, Lanuti M, et al. Evaluating pulmonary nodules. J Am Coll Radiol 2007; 4: 422 \200\223426. Winer-Muram HT. The solitary pulmonary nodule. Radiology 2006; 239: 34 \200\22348. Summary The incidental \201 nding of a SPN on CXR or CT is common. The possibility of mal ignancy must be considered. The aim of management is curative surgery for early cancers whi lst preventing the morbidity associated with resection of be- nign lesions. It is vital to involve the patient in the compli- cated decisions involved in the investigation and treatm ent of pulmonary nodules. AUTHOR \200\231S TIPS \200 Cancers (primary and secondary) that present as a SPN may be curable. Always compare curren t imaging with previous imag- ing if available. Pulmonary nodules with diagnostic imaging f eatures and solid nodules that are stable for over 2 years are benign. Part-solid and non-s olid nodules require longer follow-up. Estimate the probability that the SPN is malignant ( PCa). A risk calculator is available online at www. chestx-ray.com. If PCa is high (>60%) c onsider VATS and resection. If PCa is low (<5%), observation is appropriate. Lesions with i ntermediate Pca (5-60%) require further investi- gation. Lesions <8mm are too small to biop sy or use PET; follow-up with CT. New nodules detected during follow-up should be investiga ted independently. Patient preferences and operative risk must be consid- ered, particularl y if recommending invasive tests such as VATS. Discuss the risks and bene \201 ts of eithe r inva- sive intervention or observation. This page intentionally left blank J CALVERT ALAN MORICE 50 3.7 Wheeze Wheeze is one of the commonest medical presentations and always implies airway obstruction. Asthma or COPD are the most likely diagnoses in \201 rst world adults but such generaliz ation is not possible in developing world popula- tions where viral, bacterial and parasiti c infection may be important or in children where congenital causes for wheeze must also be considered. Table 3.7.1 Causes of adult wheeze by speed of onset/ chronicity (continued) Adults \200 \200 Slow onset COPD Primary endobronchial tumors Endobronchial metastasis (colon, breast, melanoma, kidney , pancreas) Tracheal stenosis Vocal cord paralysis Asthma Churg \200\223Strauss/pulmonary e osi- nophilia syndrome De \201 nition Wheezing is a high-pitched, continuous sound produced as the result of obst ruction at any level within the airways. It is generated as the airway walls oscillate in r esponse to the acceleration of air through a narrowed lumen. Flow may be impeded by intralu minal obstruction or extrinsic compression. \200 \200 \200 Approach Correct diagnosis depends on complete assessment of the patients history and physi cal examination. Table 3.7.2 Causes of wheeze in infants and young children by speed of onset/chronicity History For re \201 nement of the differential diagnosis the following factors must be tak en into consideration: \200 \200 \200 \200 \200 Children \200 \200 \200 \200 \200 Acute onset Infections e.g. bronchiolitis, pertussis Re \202 ux/aspiration Asthma/wheezing syndromes P neumonia Anaphylaxis Foreign body aspiration Age of the patient (Tables 3.7.1 and 3.7.2). Speed of onset of symptoms. Potential triggers (occupational, infectious, atopic). Past medical history. Family history. \200 \200 \200 \200 \200 \200 \200 Slow onset Congenital anomalies Bronchopulmonary dysplasia Bronchomalacia Vascular rings Cystic \201 brosis Tracheal stenosis Vocal cord paralysis Asthma Physical examination The level and nature of the obstruction in part determines the nature of the wheeze. During physical examination it is important to distinguish the following fea tures: \200 \200 \200 \200 Wheeze vs stridor. Monophonic vs polyphonic wheeze. Unilateral vs symmetrical wheeze. The p resence of symptoms in inspiration or expiration. Stridor is a harsh, inspiratory, monophon ic sound loudest centrally on examination of the thorax which implies central airway obstru ction. Wheeze is higher pitched and audible on more general examination of the chest. Monop honic wheeze implies \201 xed obstruction of medium- sized airways whilst polyphonic whee ze, which is usually bilateral, implies obstruction in medium to small airways. Unilateral wheeze suggests a \201 xed obstruction such as an endobronchial tumor or extrinsic compre ssion causing partial airway obstruction, e.g. as the result of vascular en- largement or l ymphadenopathy, a foreign body or airway stenosis (congenital or acquired). Investigations Laboratory Few laboratory investigations assist in diagnosis of wheeze - par ticularly at the time of presentation. The following tests may assist in investigation: Spe ci \201 c IgE (RAST testing): the presence of IgE speci \201 c for inhaled or food allerg ens may indicate an atopic precipitant for wheeze. A signi \201 cant association between a topic sensi- tisation and wheeze is generally not observed until after the age of 4 years. In adults a general screen for sensitisation to inhaled aeroallergens may include testing f or cat dander, house dust mite, and a mix of tree or grass pollens \200\223 selected on th e basis of seasonality of symptoms reported by the patient. If allergic bronchopulmonary as pergillus is suspected then testing for total IgE, speci \201 c IgE to aspergil- lus, aspe rgillus precipitins (IgG) and sputum examination for fungal hyphae is required. Where avail able skin prick testing can be substituted for RAST testing. Serology: routine testing for immunoglobulin sub-classes may identify subjects at increased risk of respiratory infec- ti ons. In children in whom an infectious cause for symp- toms is suspected blood for viral se rology can be taken and stored for comparison with results of a paired sample taken 4 \200 \2236 weeks later, at which point antibodies raised during the acute infection should have returned to normal. Table 3.7.1 Causes of adult wheeze by speed of onset/ chronicity Adults \200 \200 \200 \200 \200 \200 \200 Acute onset Asthma (exacerbations) Congestive heart failure Pneumonia Pulmonary embolism Anaphylaxis As piration syndromes Foreign body aspiration Vocal cord dysfunction CHAPTER 3.7 Wheeze 51 Appropriate culture of nasopharyngeal aspirates may also be of assistance in identifying in fectious causes of wheeze in children. Finally if tuberculosis is suspected then Man- toux testing or testing for T cells reactive to M. tuberculosis proteins (Elispot, Quantiferon G old) can be considered. Autoantibody testing: de \201 nitive diagnosis of pulmonary vas- c ulitis is likely to require tissue biopsy obtained via VATS or \201 breoptic bronchoscopy but autoantibody testing may be of assistance in suggesting a possible diagnosis. Two-thir ds of subjects with Churg \200\223Strauss syndrome will have a posi- tive p-ANCA (anti-nucl ear cytoplasmic antibody) and anti- MPO detected. Subjects are also likely to have a periph eral eosinophilia (>10%). 90% of subjects with extensive We- gener \200\231s granulomatosis and 75% with limited Wegener \200\231s will have a positive c-ANCA and staining for anti P R-3. Cystic \201 brosis: in children with recurrent respiratory tract infections, fat mal absorption or a number of other sugges- tive symptoms (see Chapter 11) testing for cystic \201 brosis should be considered. In specialist centers this may involve sodium sweat test ing. Alternatively genetic testing for com- mon CF-genotypes is widely available. not preclude foreign body aspiration and in such cases direct bronchoscopic visualization o f the airways is mandatory. Lung function testing In adult patients a reduced FEV1 (forced expiratory volume in 1 secon d) indicates airway obstruction. Reversibility of the degree of obstruction by \211 15% ( if this is >150ml) is diagnostic of reversible air \202 ow obstruction. Where spi- rometry is normal peak \202 ow variability of >20% on a peak \202 ow diary or a positive respo nse to an inhalational chal- lenge such as methacholine may assist in diagnosis. Flow volum e loops have a characteristic appearance in asthma with scalloping in the mid portion of th e expiratory \202 ow loop. In subjects with a compatible exposure history an FEV1 of less than 80% predicted with an FEV1/FVC ratio of <70% is considered diagnostic of COPD. Flow-v olume loops are most frequently used for differenti- ing between intra and extra-thoracic a ir \202 ow obstruction. Three patterns are recognized. Variable intrathoracic, vari- able extrathoracic and \201 xed air \202 ow obstruction. Where the obstruction is \201 xed, limitation in the inspiratory and expiratory \202 ow volume loops will be seen (Fig. 3.7 .1). Vari- able extrathoracic airway obstruction (e.g. bilateral vocal cord paralysis) is a ssociated with a truncated inspiratory limb due to the area of obstruction being drawn inwa rds during the inspiratory maneuver, so limiting \202 ow, and blown apart during expirati on. Conversely variable intra- thoracic \202 ow obstruction is associated with a truncate d expiratory loop but normal inspiratory limb. Radiological investigation A postero-anterior (PA) or lateral CXR may be normal in wheezing patients however the presence of lobar collapse/ volume loss may indicate proximal airways obstruction and areas of atelectasis may suggest pulmonary embolus. If pa- renchymal in \201 ltrates are present they may suggest infec- tion or a vasculitic cause for symptoms. E xamination for congenital abnormalities will be facilitated by contrast CT. Where detailed examination of the lung parenchyma is necesary high resolution CT scanning is required. New er modalities such as spiral CT with multi-planar and 3D re- constructions allows assessmen t of airways in their long axis which may assist in diagnosis of obstruction. Speci \201 c conditions Bronchiolitis Bronchiolitis is the commonest cause of wheeze in in fants. Respiratory syncytial virus (RSV) should be considered in children aged less than 24 months during the epidemic sea- son between November and April. Typical associated symptom s include low grade fever and rhinorrhoea. Coro- naviruses are also commonly associated wit h wheezing in younger children, in \202 uenza A and adenovirus are found in older children and rhinovirus is found in children of all ages. Wheeze in the context of infection in inf ants occurs as the result of mucosal oedema leading to narrowing of the airway lumen. Bronchoscopy Where obstruction in the central or segmental airways or a dynamic abnormality such as tracheomalacia is suspected \201 breoptic bronchoscopy is required. Rigid bronch oscopy is the method of choice for removal of foreign bodies. It should be noted that norma l radiographic examination does a b c d e Expiration + w o F l Volume Volume Volume Volume Volume \210\222 Inspiration a: Normal b: Intrathoracic obstruction c: Restriction d: Variable extrathoracic obstruction e: Fixed airway obstruction Fig. 3.7.1 Flow volume loop demonstrating \201 xed airway obstruction. J CALVERT 52 of the vocal cords during a wheezing episode with obser- vation of adduction of the anterio r 2/3 during inspiration. Asthma may co-exist with VCD \200\223 bronchoprovocation testing may be safely carried out to distinguish VCD from variable air \202 ow obstruction as the result of asthma. Treat- ment is challenging and often includes breathing re-training with a specialist physiotherapist and psychological support. Asthma and COPD are the commonest clinical conditions associated with wheeze in adults. They are covered in detail in Chapter s 4 and 5. Vocal cord dysfunction (VCD) VCD is inappropriate adduction of the vocal cords during inspi ration, resulting in marked inspiratory stridor. This is often misdiagnosed as asthmatic wh eeze resulting in treat- ment with escalating doses of glucocorticoids. This is gen- erally ineffective at relieving symptoms leading to increased psychological and physical morbidit y in the patient. Preva- lence is highest in women aged 20 \200\22340 years. Subjects have normal lung function during testing or a \202 ow volume loop consistent with variable ext rathoracic \202 ow obstruction. On arterial blood gas analysis the A \200\223a gradient w ill be nor- mal. The gold standard for diagnosis is direct visualization This page intentionally left blank C HILL & N MASKELL 54 3.8 The acute admission with a new unilateral pleural effusion Background Undiagnosed pleural effusions are a common reason for admission to the Medical A dmission Unit (MAU). Their clinical presentation ranges from an asymptomatic patient with a n incidental \201 nding on a CXR to a patient in extremis with severe dyspnoea and cyanos is. The management focus of these patients should be aimed at quick relief of troubling sym ptoms with prompt targeted investigations to obtain an early diagnosis whilst undertak- ing as few invasive procedures as possible. A plain CXR, focused history, thorough examination and diagnostic tap are often all that is necessary to make a diagnosis. This should be eas ily achievable by the team on take. Clinical presentation The main presenting features of effusions are cough, dys- pnoea and c hest pain. Despite this, many patients are asymp- tomatic with an effusion \201 rst being found on examination or their admission CXR. Identifying the degree of respiratory comprom ise caused by the effusion is essential, as this is a deciding factor in where the patient may be best managed. It also helps to point towards an underlying cause; particularly in ca ses of pulmonary embolism where the degree of dys- pnoea may be out of proportion to the si ze of the effusion. History On a busy MAU it is essential to be able to take a focused history ensuring all the most salient points are addressed. For any patient with an effusion this should include: \200 Any evidence of associated infection \200\223 pyrexia, fevers, sweats, presence, or absenc e of a productive cough. Associated constitutional symptoms \200\223 particularly point- i ng towards an infective or malignant cause. Skin, joint or eye symptoms raising the possibi lity of underlying connective tissue disease. A full occupational history including any pre vious asbes- tos exposure \200\223 > 90% of patients with mesothelioma develop a pleural e ffusion and its incidence is continuing to rise (see Chapter 14.7). A thorough past medical history especially including any previous malignancies \200\223 breast cancer in particul ar can recur 10 \200\22320 years later, presenting with a unilateral pleu- ral effusion. Ri sk factors for TB including foreign travel and place of birth. A full drug history \200 \223 over 40 drugs can cause pleural effusions (further details in Chapter 14.2 or at www. pneumotox.com). Key questions to ask yourself when seeing a patient with an undiagnosed pleural effusion on the MAU 1 Is this patient septic? If so it is likely that they will need to stay in for further inves tigation and management of their likely pleural infection. Is the patient symptomatic? If n ot, and pleural infection is unlikely, could they be investigated as an urgent out- patient ? Before discharge 30ml of pleural \202 uid under ultrasound guidance, needs to be remove d and sent for analysis (also see Chapter 14.2). An urgent out- patient CT thorax with pleu ral contrast also needs to be arranged with rapid clinic follow up (Fig. 3.8.1). If their m ain symptom is breathlessness (and pleural infection is unlikely) together with a moderatel y large pleural effusion on chest radiograph, then removing 1 \200\2231.5L with a ven \202 on and three-way tap will give relief of symptoms, whilst leaving some of the \202 uid i n situ for the CT scan and possible thoracoscopy if appropriate. After this \202 uid has been removed you need to ask could this patient now go home and have an urgent out-patient appointment after a CT thorax? 2 3 Examination Chest examination can provide clues to the underlying cause of an effusion but examination of associated systems often produces the crucial diagnostic signs. Lymphadenop- athy, intra-abdominal masses, cachexia and focal neurology can all indicate a malignant ca use. Examination of joints, eyes and skin must be performed if there is any suspicion of un derlying connective tissue disease. Looking for sup- porting signs of cardiac failure is al so important. The cardinal signs of an effusion are \200 \200 \200 \200 \200 4 Do they require an urgent chest drain (e.g. empyema and haemothorax)? If so are you adequ ately trained to insert one? If not, you need to \201 nd an appropriately trained colleag ue. In addition, wherever possible, a chest drain should always be inserted with ultrasound guidance. Reduced chest expansion. Reduced tactile vocal fremitus. Stony dull percussion note. Quiet breath sounds. Patch of bronchial breathing above effusion. Initial investigations CXR Despite the multiple imaging modalities available a plain CXR is still the best initial investigation for a pleural effu- sion. A lateral X-ray is able to pick up 50ml of \202 uid, whilst 200ml is needed to be visible on a PA \201 lm. However some pleural effusions can be easily missed. These include: \200 Subpulmonary effusions \200\223 due to \202 uid accumulating between diaphragm and infer ior part of the lung, they often mimic a raised hemidiaphragm. Fig. 3.8.1 CT with pleural contrast showing a pleural effusion with enhancement of the nodu lar pleural thickening. CHAPTER 3.8 The acute admission with a new unilateral pleural effusion 55 A patient on ITU will often have a supine chest radio- graph. In this situation a pleural e ffusion will be distrib- uted eveningly (if not loculated) over the posterior hemithorax, s een as diffuse opaci \201 cation on the supine \201 lm. Diagnostic pleural aspiration All patients with an unilateral pleural effusion should have a diagnostic aspiration. This is easily done with a 21F bore needle on the MAU. It should b e sent for: Biochemistry: \200 Ultrasound With an almost 100% sensitivity for \202 uid ultrasound can detect an effusion as small as 50ml (Fig. 3.8.2). It is particu- larly useful in detecting loculation and ide nti \201 es a safe site for aspiration and/or chest tube insertion. Ideally, all patients should undergo this type of imaging. Respiratory SpR \200\231s should be aiming to obtain a certi \201 cate of level 1 competency in pleural ultrasound during their training. This w ould then allow them to undertake this task on the MAU. Otherwise departmental imaging is r ecommended. Protein, LDH \200\223 to help differentiate the transudates from exudates. Glucose \200 \223 low levels seen in pleural infection and rheu- matoid effusions. pH \200\223 A pH <7. 2 is an indication for chest tube drainage in cases of pleural infection. However, it is im portant to remember that in cases of advanced malignancy the pH may also be low. Cytology: \200 At least 15 mls must be sent, ideally in a container con- taining citrate as this reduces t he risk of clots. It also allows the sample to be stored at four degrees Celsius for 4 days \200\223 useful over a weekend! The sensitivity of cytology is around 60% but this can be increased by sending a second sample. If there is any suspicion of Lymphoma. Flow cytometr y is recommended. Microbiology: \200 Sending samples in blood culture bottles and a universal container increases the yield. A g ram stain should be performed on all samples as well as AAFB and TB culture. Please \201 nd further details in Chapter 14.2. Key points \200 Many patients with pleural effusions can be managed and investigated safely as outpatients. Early CT with contrast prior to \202 uid drainage provides more accurate diagnosis in un derlying pleural disease. Always use ultrasound when undertaking pleural proce- dures. Alwa ys ask yourself \200\223 does this patient really need a chest tube now. If so, am I prope rly trained to insert it safely? Fig. 3.8.2 Ultrasound image of a pleural effusion. D= diaphragm, P= pleural \202 uid, L= liver, and B = lung CT Most patients with an undiagnosed pleural effusion will require a CT thorax at some stag e. CT is especially useful to: \200 \200 Differentiate between empyema and lung abscess. Identify any underlying lung disease which may affect fur- ther management. Allow visualization of an underlying mass lesion obscured by \202 uid on the plain \201 lm. Stage any underlying malignancy by assessing its spre ad throughout the body. Where malignancy is likely it will determine if there is any nodula r pleural thickening. amenable to CT guided biopsy in patients unsuitable for thoracoscopy (see Fig. 3.8.1). Further reading Light RW, Gary Lee YC (eds.). Textbook of Pleural Diseases, 2nd edn. London: Edward Arnold Publisher Ltd, 2008. Maskell NA, Butland RJA. BTS guidelines for the investigation of a unilateral pleural effusion in adults. Thorax 2003; 58(2): 8 \200\22317. Blood tests Essential initial blood tests that should be performed in all new patients pres enting with a pleural effusion are: \200 FBC & CRP \200\223 to identify possible underlying infection and allow monitoring of respo nse to treatment. Clotting screen \200\223 to allow correction of any abnormali- ties prio r to any invasive procedures. Liver function tests and calcium \200\223 often abnormal in malignancy. W MAN & M HIND 56 3.9 Unexplained respiratory failure The introduction of bedside ABG measurement and non- invasive ventilation has revolutionize d the management of respiratory failure in the acute setting. The history, exami- nation an d initial investigations of these patients usually points to a straightforward diagnosis an d subsequent man- agement plan. In this section we will highlight a clinical ap- proach to patients where the cause of respiratory failure is not obvious on initial assessment. Respi ratory failure is commonly classi \201 ed into 2 types de- pendent on the arterial partial pressure of carbon dioxide; type 1 \200\223 hypoxaemia (PaO2 < 8kPa) with a normal or low carbon dioxide, and type II \200\223 hypoxaemia and hypercapnoea (PaO2 < 8kPa, PaCO2 >6kP a). The underlying pathophysiol- ogy of these disorders is quite different. Type 1 respirat ory failure is due to an increased alveolar \200\223arterial (A \200\223a) gradi- ent with a normal or increased ventilatory response. This is a \201 nal common path for many disea ses not just those with lung pathology, e.g. left ventricular failure. Patients present- in g with type 2 respiratory failure or ventilatory failure can have a normal A \200\223a grad ient and it is these patients that we will consider below. A logical approach is to \201 rstly to exam- ine the causes of unexpected respiratory failure Airways obstruction/ Unrecognized COPD/ severe asthma mixed Obstructive sleep apnoea/obesit y/ muscle weakness History A careful and thorough history with clear timelines, par- ticularly for neuromuscul ar weakness, often points to a particular disorder. Sleep disturbance is often an early fea ture of many neuromuscular disorders and may predate breathlessness. Shoulder pain might su ggest neuralgic amyotrophy. Orthopnoea, breathlessness when bathing or swimming is suggesti ve of diaphragm weakness. Swal- lowing and speech dif \201 culties are important clues. Co llat- eral history from partners and/or family is important par- ticularly if the patient p resents with a reduced level of consciousness. Examination A full examination can reveal subtle diagnostic clues; the rate, depth and patt ern of breathing should be noted e.g. abnormal slowing of breathing seen in opiate use or C heyne \200\223Stokes periodic respiration seen in cerebral and cardiac disease; scars and e vidence of previous surgery might point to phrenic nerve injury; neurological signs such as fatigability, fasciculation, myotonia, and weakness should be looked for; abdominal parado x (inward drawing of the abdomen during inspiration) points to diaphragm weakness. Causes of unexplained respiratory failure Failure of ventilatory drive Neural suppression O piates Overdoses Metabolic alkalosis Polio/postpolio Brainstem stroke Arnold \200\223Chiari malfor mation Syringobulbia CNS infection (encephalitis, toxoplasmosis, tuberculoma) Brainstem tum or Brainstem disease Initial investigations ABGs \200 \200 \200 \200 Assessment of blood gasses off supplementary oxygen. The level of PaCO2. The base excess/ba se de \201 cit. A \200\223a gradient (normal <2.5 changes with age). Failure of the ventilatory pump Myopathies Chest radiograph/HRCT This may reveal evidence of unsuspected lung disease Acid maltase de \201 ciency Duchene muscular dystrophy Ulrich \200\231s muscular dystrophy Myotonic dystrophy Limb-girdle dystrophy In \202 ammatory myopathies Motor neuron disease Neuralgic amyotrophy Guillain \200\223Barr syndrome Spinal muscular atrophy (II-IV) Cord injury Myasthenia gravis Lambert \200\223Eaton syndrome Post-muscle relaxants e.g. suxamth onium Anti-cholinesterase poisoning (organophosphate poisoning) Critical care neuropathy/my opathy Obesity Scoliosis Thoracoplasty Flail chest Pneumothorax or large effusion Ankylosin g spodylitis Lung function \200 \200 \200 \200 \200 Unexpected airway obstruction. Reduction in vital capacity (chest wall or neurological). Fa ll in supine VC (diaphragm weakness). If supine VC <1 liter then this likely to be cause of failure. Mouth pressure, sniff pressures and trans-diaphragm pressures can be useful in sp eci \201 c situations. Neuropathy Other tests \200 Sleep study \200\223 to exclude REM related hypoxaemia, obstructive sleep apnoea. CK \200 \223 elevated in some myopathies. ANA, ANCA \200\223 repeated measurements are helpful in vasculitis. Acetyl cholinesterase receptor antibodies \200\223 myasthenia gravis. ECG \200\223 assessment of right and left heart function, esti- mation of pulmonary artery pres sure and exclusion of structural lesions is often helpful. Electromyography/nerve conductio n studies \200\223 diagnos- tic for MND, myotonia, myasthenia. Muscle biopsy \200\223 aci d maltase de \201 ciency. Neuromuscular junction \200 Mixed Chest wall abnormalities CHAPTER 3.9 Unexplained respiratory failure 57 Brainstem imaging \200\223 gadlinium-enhanced MRI to exclude to ventilate adequately unaided or clear bronchial secre- tions. Reversal of muscle relaxan t initially showed a good response but then ventilation deteriorated again. She remained in tubated and ventilated, and eventually re- quired a tracheostomy. There was a history from the daughter that the patient had been complaining of inter- mittent tiredness and muscle w eakness for several months before the operation. Electrophysiological studies showed a decr ement in compound muscle action potential ampli- tude on repetitive nerve stimulation (Fig. 3.9.2), whilst single \201 bre EMG demonstrated abnormal jitter. Histology from the medi astinal mass con \201 rmed a thymoma. Tensilon test demonstrated an immediate improvement in maximum inspiratory pressure measured via the tracheos- tomy from 18cmH2O to 65cmH2O. Se rologic testing con- \201 rmed autoantibodies to the acetylcholine receptor. The patient was started on pyridostigmine and underwent plas- mapheresis, followed by prednisolone. The patient was eventually decannulated, and managed without the need for non-invasive ventila tion. Diagnosis \200\223 myasthenia gravis. structural lesions CSF sampling \200\223 lumbar puncture to exclude CNS in \202 am- mation/infection Clinical cases Case 1 A 65-year-old man, following an elective left total hip replacement, was noted to have frequent oxygen desatura- tions in recovery. Daytime ABGs on room air dem onstrated a PaO2 8.5kPa and a PaCO2 6.8kPa. Chest radiograph was normal. Further questionin g of his wife revealed a several year history of heavy snoring, witnessed apnoeas, and unre freshing sleep. The patient also suffered from signi \201 - cant daytime hypersomnolence a nd had been involved in a car accident 4 months previously where he dozed off during drivin g and crossed the central reservation. Exami- nation revealed a BMI of 36 and a bull neck. Overnight oximetry is shown in Fig. 3.9.1. The patient was com- menced on CPAP therapy with good symptomatic effect, and at 3 months, ABGs on air revealed a PaO2 10.5kPa and a PaCO2 5.8kPa. Diagnosis \200\223 severe obstructive sleep apnoea.