numerous essential regular medications is sometime diffi- cult in patients with mental heal th problems. Studies on a bronchoscopic \200\230equivalent of LVRS \200\231, using endobro nchial one-way valves, are currently underway, which may become an option for patients who are not fit enough for a major surgical procedure. CASE 37 323 Further reading Ambrosino N , Simonds A ( 2007 ). The clinical management in extremely severe COPD . Respir Med ; 101 : 11613 \200\223 11624 . Celli BR , Cote GG , Marin JM , Casanova C , Montes de Oca M , Mendez RA et al. ( 2004 ). T he body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic ob structive pulmonary disease . N Engl J Med ; 350 (10) : 1005 \200\223 1012 . Glanville AR , Estenne M ( 2003 ). Indications, patient selection and timing of referral fo r lung transplantation . Eur Respir J ; 22 : 845 \200\223 852 . National Emphysema Treatment Trial Research Group ( 2003 ). Cost effectiveness of lung-volume reduction surgery for patients with severe emphysema . New Engl J Med ; 348 : 2 092 \200\223 2102 . Patel N , DeCamp M , Criner GJ ( 2008 ). Lung transplant and lung volume reduction surgery versus transplantation in chronic obstructive pulmonary disease . Proc Am Thorac So c ; 5 : 447 \200\223 453 . Sayeed RA , Waddell TK ( 2008 ). Lung volume reduction surgery . In: Core Topics in Cardiothoracic Critical Care ( Klein A , Nashef SAM , eds) Cambridge University Press , cha pter 52, pp. 392 \200\223 396 . Case 38 A 67-year-old lady was referred with 6 months of progressive breathlessness on exertion. He r past medical history was of limited Wegener \200\231s granulomatosis, diagnosed 15 years previously, causing recurrent nasal and sinus disease and requiring frequent sinus irrigati on. She had remained ANCA negative over recent years and was currently on no immunosuppress ive treatment, but had been treated with steroids, cyclophosphamide and azathioprine shortl y after diagnosis. On examination, resting Sa O 2 was 97%, there were fairly harsh inspirat ory and expiratory sounds (no frank stridor) and signs of previous Wegener \200\231s with c ollapsed nasal bridge. Full examination was otherwise normal. Table 38.1 Pulmonary function tests Measured % Predicted PEFR(L/min) 140 41 FEV1(L) 1.8 88 FVC(L) 3.0 120 FEV1/FVC 61 RV(L) 3.5 133 TLC(L) 5.5 114 VA(L) 4.1 86 TLCO(mmol/min/kPa) 5.47 76 KCO(mmol/min/kPa/L) 1.33 89 CASE 38 325 Fig. 38.1 CXR. Questions 38a) What abnormality is suggested by the pulmonary function values (Table 38.1), and what further pulmonary function test would help? 38b) Interpret the CXR ( Fig. 38.1 ). 38c) What two further investigations are required? 38d) What is the likely diagnosis? CASE HISTORIES IN RESPIRATORY MEDICINE 326 Answers 38a) What abnormality is suggested by the pulmonary function values (Table 38.1), and what further pulmonary function test would help? The pulmonary function (Table 38.1) shows mild airflow obstruction (and a small degree of a ir trapping). However, the peak flow is markedly reduced in comparison to the FEV 1 . This suggests upper airway obstruc- tion, and the Empey index \200\224FEV 1 (in ml)/PEFR(in L/mi n) \200\224is 12.9. An Empey index of >10 is strongly suggestive of expiratory upper airway obstruction. Suspicion of upper airway obstruction would be supported by examining a flow-volume loop ( Fig. 38.2 ). Fig. 38.2 Flow-volume loop. Expiration upwards, inspiration downwards, TLC far left of grap h. Rectangles indicate normal range values, given the patient \200\231s VC. 38b) Interpret the CXR ( Fig. 38.1 ). The CXR shows diffuse widening of the right paratracheal soft tissues, and this has a well- defined slightly convex lateral margin. The right paratracheal stripe (tracheal wall outlin ed by air either side) is only preserved inferiorly (Fig. 38.3). The SVC up against the tra cheal wall would not account for this abnormality, as it is never convex, and would not app ear as dense as this, especially towards the apex (Fig. 38.3). There is no convincing signi ficant tracheal indentation or narrowing (although this is just a PA projection and therefo re elliptical narrowing with reduced antero-posterior tracheal dimensions may not be seen). Possible causes of this would be a goiter (although this should deviate the trachea), medi astinal fat or lipoma (although these would appear less dense). CASE 38 327 Fig. 38.3 CXR showing preserved paratracheal stripe lower end of trachea only (arrow). 38c) What two further investigations are required? CT scan and bronchoscopy. 38d) What is the likely diagnosis? Although the precise diagnosis of the clinical finding of upper airways obstruction is not clear at this point, a possibility is further upper airway involvement from Wegener \200 \231s. The long history of nasal disease would raise the prior probability of this. Further investigation Bronchoscopy (Fig. 38.6) revealed marked narrowing of the trachea just below the vocal cord s (to a diameter of approximately 5mm, in agreement with the CT scan). Distally, past the s tenosis, the trachea appeared normal. CASE HISTORIES IN RESPIRATORY MEDICINE 328 SVC Azygous vein in the azygous fissure This accounts for the CXR abnormality \200\223 lung me dial to the azygous vein often appears very opaque. (a) (b) (c) Narrowing of upper trachea approximately 2cm below vocal cords (d) (e) Fig. 38.4 (a \200\223c) Axial images from CT neck/thorax. (d,e) Coronal reconstruction show ing narrowing of upper trachea. CASE 38 329 Fig. 38.5 Bronchoscopic view from level of the vocal cords, remaining orifice approximately 10% of normal tracheal cross-sectional area. Questions 38e) What is the diagnosis? 38f) How does the flow volume loop vary with different causes of upper airflow obstruction? 38g) How would you manage this patient? CASE HISTORIES IN RESPIRATORY MEDICINE 330 Answers 38e) What is the diagnosis? Upper airway Wegener \200\231s granulomatosis causing post-inflammatory scarring and fibros is in the trachea and a characteristic flow volume loop of fixed upper airflow obstruction. 38f) How does the flow volume loop vary with different causes of upper airflow obstruction? The appearance of the flow volume loop (FVL) in upper airflow obstruc- tion depends on whet her the level of obstruction is intra or extrathoracic, or is fixed or variable. In general, about half of the trachea is intrathoracic, and half extratho- racic. The upper extrathoracic part of the trachea is narrowed in inspira- tion as luminal pressure is suba tmospheric. It will then dilate in expiration as luminal pressure exceeds that of its surro undings as intrathoracic pressure rises. Consequently, fleshy tumors in the upper trachea w ill generally cause more airflow obstruction during inspiration than expira- tion, and henc e inspiratory stridor. In the lower trachea, in inspiration, the intraluminal pressure is h igher than the surrounding negative intrathoracic pressure and the trachea dilates. In expi ration, the lower trachea is compressed by surrounding positive intrathoracic pressure and the trachea is compressed. Therefore, with tumors in the lower trachea, stridor may be less immediately obvious as there will be more airflow obstruction in expiration than inspirati on. Clearly there may be mixed effects from tumors with more extensive upper airway involvement . The degree of differential impairment to the inspiratory or expiratory flow will also dep end on the degree to which the obstruction is fixed. A more fleshy tumor in the upper trach ea would be more likely to cause the effects above, as the obstructing elements are blown o pen in expiration. A more fibrotic or extensive submucosal tumor infiltration will cause si milar levels of inspiratory and expiratory flow limitation. Typical FVL appearances would b e: \227\206 Variable extra-thoracic upper airway obstruction (e.g. vocal cord dysfunction \200\224see case 29): relatively normal expiratory limb, flattening of inspiratory limb \227\206 Variable intra-thoracic airway obstruction: relatively normal or slight impairment of inspiratory limb, flattening of expiratory limb \227\206 Fixed upper airway obstruction: flattening of both inspiratory and expiratory limbs, so called \200\230square box \200\231 FVL. CASE 38 331 38g) How would you manage this patient? The treatment options are laser resection, tracheal dilatation or stenting with a decision made on an individual basis. In one series of 30 patients with endobronchial involvement by Wegener \200\231s (Daum et al . 1995), five had subglottic stenosis and four had tracheal or bronchial stenosis with other abnormalities including ulcerating tracheobronchitis. Thre e of these patients underwent dilatation and one had removal of granulation tissue by YAG l aser, but symptoms had recurred in three of these four patients within 10 months. Three oth er patients underwent silastic stent insertion, which provided continued symptom relief ove r up to 33 months follow-up. In another series (Utzig et al . 2002) of eight patients with tracheal stenosis and five with subglottic stenosis who all underwent tracheal multiple tra cheal dilatations, only one required stenting. Our patient underwent dilatation of her subglottic stenosis with a good symptomatic result and has remained well since. Further reading Hetzel MR ( 2003 ). Diseases of the upper airway . In: Gibson GJ , Geddes DM , Costabel U, Sterk PJ, Corrin B . (eds) Respiratory Medicine ( 3rd edn). Saunders , London , chapter 44, pp. 1048 \200\22367 . Chapman S , Robinson G , Stradling JR , West S ( 2005 ). Lung function testing . In: Oxford Handbook of Respiratory Medicine. OUP , Oxford , Appendix 1 , pp. 706 \200\223 707 . Daum TE , Specks U , Colby TV, Edell ES, Brutinel MW, Prakash UB et al. ( 1995 ). Tracheobronchial involvement in Wegener \200\231s granulomatosis. Am J Respir Crit Care Med ; 151 ( 2 ): 522 \200\223 526 . Utzig MJ , Warzelhan J , Wertzel H , Berwanger I , Hasse J ( 2002 ). Role of thoracic surge ry and interventional bronchoscopy in Wegener \200\231s granulomatosis . Ann Thorac Surg ; 74 : 1948 \200\223 1952 . Case 39 A 26-year-old man presented to the dermatologists with a 5-month history of a painless and non-itchy infiltrate in the red areas of a forearm tattoo. In addi- tion, he noticed some s mall lumps that appeared on the elbow and outer arm above the tattoo. He had noticed some m ild arthralgia over the last 3 months. There was no relevant past medical history, except t hat 2 years previously, the red areas in the tattoo had become raised but this had settled after a few weeks. Patch-testing to various dyes used in tattoos was negative. He was given Tacrolimus cream o n the assumption it was an allergic reaction to the red dye with no therapeutic effect. Som e routine tests were performed. Investigations \227\206 FBC, U&Es and liver function tests were all normal \227\206 Lung function, FEV 1 /VC, 4.3/6.1(L), ratio 70% \227\206 CXR in Fig. 39.1. Fig. 39.1 CXR. CASE 39 333 Infiltrated red pigment areas Uninvolved black pigment area Fig. 39.2 Skin tattoo (eagle). Questions 39a) What does the CXR ( Fig. 39.1 ) show? 39b) What is the likely diagnosis? 39c) What investigations would you do next? 39d) What treatment would you offer? 39e) Is the slightly low FEV 1 /VC ratio compatible with the diagnosis? CASE HISTORIES IN RESPIRATORY MEDICINE 334 Answers 39a) What does the CXR ( Fig. 39.1 ) show? The CXR ( Figs. 39.1 and 39.3 ) shows bilateral hilar node enlargement and azygos node enla rgement. Azygos node enlargement Left hilar node enlargement Right hilar node enlargement Fig. 39.3 Hilar area of CXR. 39b) What is the likely diagnosis? The likely diagnosis is sarcoidosis. Infiltration with sarcoid granuloma of scars and tatto os is well recognized, and has been described particularly where there is red pigment, but also with navy blue and black pigments. One assumes the infiltration 2 years previously was the start of his sar- coidosis. Other causes of nodal enlargement would have to be conside red in the absence of this pointer. 39c) What investigations would you do next? Biopsy of the skin lesion showed typical non-caseating granuloma. A high-resolution CT scan of the chest might show typical micronodules in a subpleural, fissural and broncho-vascula r distribution, and would have been useful if the diagnosis had not already been secure; bu t such a typical radiological pattern is not always present. 39d) What treatment would you offer? Treatment would consist of steroid cream to the tattoo, ibuprofen and paracetamol for the a rthralgia. 39e) Is the slightly low FEV 1 /VC ratio compatible with the diagnosis? The slightly low FEV 1 /VC ratio may be due to the sarcoidosis, as there can be small airwa ys obstruction, thought to be due to granulomatous CASE 39 335 involvement of small airways, usually, but not exclusively, when there is visible infiltrat ion on the CXR. It can occur without a fall in compliance and VC (that would suggest an add itional interstitial component), and may be evident on HRCT scanning as expiratory air trap ping. Progress Symptoms resolved with simple treatments. Eight months later, dyspnoea and the tattoo infil tration returned. A repeat CXR was arranged and the radiologist organized an HRCT scan of t he lungs. Before this appointment, the patient went on a beach holiday to Weymouth for 2 we eks. He became lethargic, with polyuria and thirst, and was admitted as an emergency on his return. Investigations \227\206 Urea 15mmol/L, Creatinine 411 mol/L, K + 5.3mmol/L \227\206 See also Figs 39.4 and 39.5 . CASE HISTORIES IN RESPIRATORY MEDICINE 336 Fig. 39.4 CXR Fig. 39.5 High resolution CT scan of lungs. CASE 39 337 Questions 39f) What do the CXR ( Fig. 39.4 ) and HRCT ( Fig. 39.5 ) show? 39g) What has happened? 39h) What test would you urgently order next? 39i) What is the relevance of the beach holiday? 39j) What is the treatment? CASE HISTORIES IN RESPIRATORY MEDICINE 338 Answers 39f) What do the CXR ( Fig. 39.4 ) and HRCT ( Fig. 39.5 ) show? The CXR now shows subtle infiltration with multiple small soft nodules, but the hilar have become essentially normal. Multiple soft pulmonary nodules Fig. 39.6 Magnified area of CXR. The HRCT shows a diffuse nodular pulmonary infiltrate with some interlobar thickening compa tible with, but not totally diagnostic of, sarcoidosis. There is no fissural nodularity, fo r example. 39g) What has happened? He has developed renal failure due to several possible complications of sarcoidosis. Hyperc alcaemia/hypercalcuria can damage the kidney slowly (though nephrocalcinosis) or acutely. A bout 40% of patients with sar- coidosis have hypercalciuria, but only about 15% develop hyp ercalcae- mia. Hypercalcaemia also reduces responsiveness to ADH, producing polyuria and en couraging dehydration with pre-renal failure. A granulo- matous nephritis can damage tubula r function but is a rare cause of significant renal impairment. 39h) What test would you urgently order next? A plasma calcium is required and was 3.32mmol/L on the day of admis- sion. Activated macrop hages in granuloma convert 25-hydroxyvitamin D into calcitriol (1,25(OH) 2 D 3 ), the most active version of vitamin D, CASE 39 339 thus resulting in increased absorption of calcium from the gut, and resorption from bone. T his can occur in any granulomatous disease, not just sarcoidosis. 39i) What is the relevance of the beach holiday? Sunlight from his beach holiday further increased the conversion of vitamin D to, ultimatel y, the active form, calcitriol, thus exacerbating the hypercalcaemia. 39j) What is the treatment? Treatment is required with prednisolone (1mg/kg) and as generous intra- venous fluids as th e renal failure will allow. If hypercalcaemia alone is the reason for the renal failure, it will respond quickly. If dominantly neph- rocalcinosis or a nephritis, the response is slo wer; failure to achieve nor- mal renal function is associated with renal scarring. Further short-term calcium suppression can be obtained with pamidronate, if required. Long-term con trol of hypercalcaemia requires sun avoidance, a low calcium diet, low-dose steroids or hyd roxychloroquine (via suppression of granuloma activity). Progress The hypercalcaemia resolved within 10 days, and the renal failure took nearly 4 months to f ully resolve. Following a total of 7 months of steroids, these prob- lems have not returned . Case 40 A 44-year-old man was referred for evaluation following three episodes of small-volume haem optysis (blood streaking of sputum only) in association with cough and purulent sputum prod uction. His symptoms had resolved and he reported no further haemoptysis in the month prior to out-patient review. However, he did mention intermittent epistaxis for \200\230many ye ars \200\231. He was a current smoker of 40 cigarettes a day (45 pack years). On examinatio n, he had multiple telangiectases on his lips and tongue. He was not anemic or cyanosed, bu t his peripheral oxygen saturation was 91% on room air whilst sitting. His oxygen saturatio n rose to 95% when supine (SaO 2 88% standing). His chest was clear. His CXR ( Fig. 40.1 ) and full pulmonary function testing, including transfer factor and diffusion capacity, were normal. Fig. 40.1 CXR CASE 40 341 Questions 40a) What is the likely diagnosis? 40b) What investigation would you do next? CASE HISTORIES IN RESPIRATORY MEDICINE 342 Answers 40a) What is the likely diagnosis? The history of epistaxis and physical findings of mucocutaneous tel- angiectasia suggest a diagnosis of hereditary haemorrhagic telangiectasia (HHT). Orthodeoxia (fall in arterial ox ygen levels when upright) suggests associated pulmonary arteriovenous malformations (PAVM) \200\224shunting and consequent desaturation are accentuated when upright due to an increas ed blood flow (with gravity) through, predominantly basally situ- ated, AVM. NB: a normal CXR does not exclude the diagnosis; clinically important PAVMs are often below the resolution of CXR. 40b) What investigation would you do next? Contrast-enhanced thoracic CT is an appropriate next investigation. Contrast is not always needed, depending on institutional expertise. CT identifies PAVM and whether they are amena ble to embolization. Additional lesions elsewhere in the lungs can be identified. Some cent ers would use contrast echocardiography if there was no clinical evidence of shunting prese nt. Pulmonary angiography should usually be reserved for patients being considered for embo lization. Progress On directed questioning, the patient reported that both his father and daughter also suffer ed with frequent epistaxis. A CT pulmonary angiography was performed ( Fig. 40.2 ) and demonstrated arteriovenous malfo rmations anteriorly within the right-upper lobe (with a leading vessel identified, Fig. 40. 2a) and in the postero-lateral segment of the right-lower lobe (arrowed, Fig. 40.2b). Elsew here, multiple tiny AVMs were also identified. CASE 40 343 (a) (b) Fig. 40.2 CT pulmonary angiogram. Question 40c) What would you do next to assess the clinical significance of the PAVM? CASE HISTORIES IN RESPIRATORY MEDICINE 344 Answer 40c) What would you do next to assess the clinical significance of the PAVM? All PAVMs are significant due to arterial hypoxaemia and potential paradoxical embolic stro ke (Shovlin et al . 2008). The degree of right- to-left shunting, as the shunt fraction, ca n be measured. Clinically significant PAVMs increase the fraction of cardiac output that bypasses the pulm onary capillary bed. In normal subjects, the intrapul- monary shunt is <2.5% of cardiac out put and is mainly composed of left ventricular muscle venous blood draining directly into t he left ventricle. CASE 40 345 Progress Radionuclide perfusion lung scanning was performed and an estimated shunt fraction of 12% c alculated. Questions 40d) How is the shunt fraction calculated via perfusion lung scanning? 40e) What other methods of shunt quantification may be used? 40f) What other tests could be used to detect PAVM? 40g) What are the complications of PAVM? 40h) What therapeutic options are there for this patient? CASE HISTORIES IN RESPIRATORY MEDICINE 346 Answers 40d) How is the shunt fraction calculated via perfusion lung scanning? The shunt fraction can be calculated in normal subjects by administration of intravenous 99 m Tc-labeled albumin macroaggregates, which are nor- mally fully filtered by the pulmonary capillary bed. PAVMs allow their passage through the lungs, and thus their detection in oth er organs (e.g. kidneys and brain). Calculation of the shunt fraction is performed follow- ing differential radionuclide scanning over the lungs and right kidney (presumed to receive 10% of the cardiac output): \216\233 \216\234 \216\235 \216\236 \216\237 \216 Right kidney counts \227 correction factor \22710 Total counts injected Shunt fraction(%) = \227100 The shunt fraction is raised in 90% or more of patients with PAVM. 40e) What other methods of shunt quantification may be used? Other methods of quantification include the 100% oxygen method: \227\206 Oxygen saturation and PaO 2 are measured after breathing 100% oxy- gen for 15 \200\22320min. A mouthpiece in combination with a nose-clip is much better than close fitting masks, or a non-rebreather system, as they tend to leak and not deliver 100% O 2 . Administration of less than 100% wi ll over-estimate the shunt fraction by lowering the PA O 2 . \227\206 The shunt can be acc urately calculated only if the mixed venous oxygen levels are known. Fractional shunt = ( pulmonary capillary O 2 c o n t e n t \210\222 arterial O 2 content ) / ( pulmonary capillary O 2 content - mixed venous O 2 content ) or more commonly written Qshunt Qtotal = ( CAO 2 \210\222 CaO 2 ) ( CAO 2 \210\222 Cv \200\223O 2 ) where Q = blood flow, C = O 2 content, A = pulmonary capillary, a = arterial and v \200\223 = mixed venous. \227\206 However, an approximation can be made making various assumptions . If (i) the arterial oxygen saturation is 99 or 100% while breathing 100% oxygen (or PaO 2 > 25kPa),(ii) the Hb is 12 \200\22316g/dL, (iii) oxygen con- sumption/cardiac output norma l, and (iv) the PaCO 2 is about 5.3 0.5kPa, then the following very simplified equation can be used. % shunt = 34 \210\222 ( PaO 2 \227 0.38 ) PaO 2 measured in kPa. CASE 40 347 For example, if there is no shunt, then the arterial PaO 2 should be about 85kPa, if it wer e 60kPa, then 34 \200\223 (60 \227 0.38) = 11% shunt. \227\206 <10% shunt is probably no rmal (i.e. the PaO 2 on 100%O 2 is > 60kPa) \227\206 10 \200\22320% is abnormal, but not usually symptomatic (i.e PaO 2 on 100% O2 is 35 \200\22360kPa). \227\206 >20% is significant and usually symptomatic (i.e. PaO 2 on 100% O 2 is <35kPa). 40f) What other tests could be used to detect PAVM? Other investigations used to evaluate intrapulmonary shunts include: \227\206 Contrast echocardiography: involves injection of agitated saline (to introduce bu bbles) into a peripheral vein whilst imaging the atria. In normal subjects the bubbles appe ar first in the right atrium, and then are trapped and dissipate in the pulmonary circulati on. In patients with an intra-cardiac shunt, the bubbles are seen in the right atrium and w ithin 1 cardiac cycle, in the left atrium. With PAVMs, after a delay of 3 to 8 cardiac cycl es (2 \200\2235 seconds) contrast bubbles are seen in the left atrium. \227\206 Contrast enhanced computed tomography: may be more sensitive than angiography in detection of PAVMs, although less able to deter- mine the exact angioarchitecture. \227\206 Pulmonary angiography: digital subtraction, or conventional, angiog- raphy is use d (there are no existing comparison studies) and remain the gold standard. Pulmonary angiog raphy is vital for treatment planning. 40g) What are the complications of PAVM? Between 15 and 33% of patients with HHT have PAVMs (which originate from the pulmonary rath er than bronchial arteries). Long-term compli- cations include: \227\206 Neurological Stroke Transient ischaemic attack (TIA) Cerebral abscess Seizure Migraine. These arise as a result of emboli reaching the cerebral circulation, bypass- ing the normal filtering system of the pulmonary capillaries, due to the right-to-left shunt, and may be the presenting feature of a PAVM. Strokes and abscesses are usually seen with feeding arter ies >3mm in diameter. CASE HISTORIES IN RESPIRATORY MEDICINE 348 More than two-thirds of cerebral phenomena seen in HHT arise due to emboli via PAVMs (the r emainder due to additional cerebral AVMs, sometimes seen in HHT). \227\206 Respiratory Massive haemoptysis (rupture of a parenchymal PAVM or endo- bronchial telangiectasia) Haemothorax (rupture of a subpleural PAVM). Symptoms may develop or worsen during pregnancy as a consequence of an increased blood volu me and cardiac output. \227\206 Pulmonary hypertension \200\224rare but may be related to defects in activin rece ptor-like kinase-1 (ALK-1), the product of one of the recognized underlying genetic mutatio ns in HHT (HHT type 2). \227\206 Other Anemia Polycythaemia Heart failure Infective endocarditis. 40h) What therapeutic options are there for this patient? Although the natural history of untreated PAVMs is unknown, approxi- mately enlarge with time. Morbidity rates of up to 50% have been reported in patients with untreated PAVMs, co mpared to 3% of those following intervention. Treatment aims to prevent complications, par- ticularly neurological, minimize progressive hypoxia and its sequelae, and reduce the inci dence of high-output cardiac failure. Current recommendations advise treatment of all symptomatic PAVMs and of those with feeding vessels \211 3mm. Options include: 1. Embolization therapy (embolotherapy) : i.e. angiographic occlusion of the feeding arteri es using steel coils or detachable balloons. This is the favored initial therapeutic choice , particularly in patients not suitable for surgery, and those with multiple PAVMs (which c an be embolized in a single session). Self-limiting pleuritic chest pain is the most common short-term complication (5 \200\22313 %). Longer term stroke and/or cerebral abscess still occur in 2%, new PAVMs may develop and recanalization of treated PAVMs is seen in 1 \200\22310%. The development of pulmonary CASE 40 349 hypertension as a consequence of embolization (iatrogenic blockade of the low resistance AV Ms), might be predicted, however, a recent study (Shovlin et al. 2008), did not show any si gnificant increase in pulmo- nary artery pressures after embolization in 40 patients with H HT. The authors excluded patients with known advanced pulmonary hyper- tension for whom avo idance of PAVM embolization is currently recommended. 2. Surgery. Options include local excision, segmental or lobar resection and PAVM ligation. However, due to the morbidity associated with a general anesthetic and thoracotomy, embolo therapy is preferred and surgery limited to those with allergy to contrast, or rarely PAVMs not amenable to embolization. Long-term follow-up . The risk of growth of undetected PAVMs, and recanalization of emboliz ed PAVMs, makes regular follow-up (clinical review and thoracic CT) prudent. Antibiotic pro phylaxis is recom- mended, in those with treated or untreated PAVMs, prior to an invasive p rocedure, to reduce the risk of infection (via loss of the filtration afforded by the lung) such as cerebral abscess and infective endocarditis. Screening of family members of those with HHT-related PAVMs is recommended, as the prevalen ce in relatives is approximately 35%. A thorough history, physical examination (with assess ment for orthode- oxia using oximetry), CXR, 100% oxygen study and contrast echocardi- ogra m are recommended screening tools in some centers. Women with HHT should also be screened before pregnancy, as there is an increased rate of h aemothorax and haemoptysis in the last half of pregnancy. Progress This patient was referred for formal pulmonary angiography and embolo- therapy was subseque ntly performed with good effect. Further reading Gossage JR , Kani G ( 1998 ). Pulmonary arteriovenous malformations: a state of the art review . Am J Respir Crit Care Med ; 158 : 643 \200\223 661 . Shovlin CL , Jackson JE , Bamford KB, Jenkins IH, Benjamin AR, Ramadan H et al . ( 2008 ). Primary determinants of ischaemic stroke/brain abscess risks are independent of severity of pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia . Thorax ; 63 : 259 \200\223 266 . Case 41 An 80-year-old woman was admitted to A&E with breathlessness. She had initially presented t o her GP with a dry cough, and was diagnosed with a viral upper respiratory tract infection . Over the following three weeks she experi- enced progressive shortness of breath on exert ion, and at presentation was breathless at rest. She denied sputum production, fevers and a ny constitutional symptoms. Her past medical history included rheumatoid arthritis, which had been diagnosed 5 years pr eviously. Her joint disease had been difficult to control on a combination of prednisolone 10mg once a day and methotrexate 15mg once weekly (with folate supplementation), and she ha d started anti-TNFa therapy three months ago with a reasonable response, enabling a decreas e in her other therapy. There was no other relevant past medical history. On examination she was tachypnoeic (35/min), afebrile and hypoxic (SaO 2 at rest 81% on roo m air). Investigations performed 3 weeks previously were compared to her admission investig ations. Investigations Blood tests: \227\206 This admission: Hb, 8.8g/dL \227\217 WCC, 12.4 \227 10 9 /L (neutrophilia) \227\217 Platelets, 602 \227 10 9 /L \227\217 Urea and electrolytes normal CRP >160mg/L. \227\206 3 weeks previously: Hb, 9.5g/dL \227\217 WCC, 9.68 \227 10 9 /L \227\217 Platelets, 395 \227 10 9 /L \227 \217 Urea and electrolytes normal CRP = 35mg/L. \227\206 Arterial blood gasses (on air): pH, 7.47 \227\217 PaO 2 , 6.2kPa \227\217 PaCO 2 , 4.1kPa CASE 41 351 SaO 2 , 81% \227\217 Base excess, \200\2230.8mM/L Bicarbonate, \200\22324mM/L. \227\206 See also Fig. 41.1 . Fig. 41.1 CXR. Questions 41a) Interpret the blood gas findings in this case. 41b) Describe the CXR findings ( Fig. 41.1 ). 41c) What is the differential diagnosis and what is the most likely diagnosis. Why? 41d) Describe two key initial investigations and their rationale. CASE HISTORIES IN RESPIRATORY MEDICINE 352 Answers 41a) Interpret the blood gas findings in this case. The arterial blood gasses show type I respiratory failure. The alveolar- arterial gradient (see case 12 for formula) is \210 8kPa (normal 2 \200\2233) \200\224this implies a substan tial V/Q mismatch. 41b) Describe the CXR findings ( Fig. 41.1 ). The CXR shows: \227\206 Bilateral volume loss \227\206 Diffuse reticular opacification with a basal and peripheral predominance \227\206 Opacification in the right-lower zone, which could be areas of atelectasis or consolidation. 41c) What is the differential diagnosis and what is the most likely diagnosis. Why? The differential diagnosis here is one of multifocal, bilateral lung infil- trates in the c ontext of rheumatoid arthritis. It includes: 1. Rheumatoid associated interstitial lung disease (RA-ILD). RA-ILD is the most common mani festation of rheumatoid lung disease. Radiologically, clinically and histologically, RA-ILD is similar to the idiopathic interstitial pneumonias, with usual interstitial pneumoni- ti s (UIP), non-specific interstitial pneumonitis (NSIP) and cryp- togenic organizing pneumoni a (COP) the most common seen in rheumatoid. In this case, the bilateral volume loss and zon al distribu- tion is in favor of UIP, whereas the relatively short history and aggressive p rogress is against this. UIP does not explain the right basal consolidation, whereas COP co uld cause this. However, COP is typi- cally associated with bilateral infiltrates (as oppos ed to reticulation as seen here) and preserved lung volumes on CXR. 2. Drug induced lung disease. Pulmonary effects can result from a host of medication for the treatment of RA. Agents to consider are: Methotrexate. Although infective complications are reported in patients treated with methot rexate (including PCP and fungal pneumonias), the most common pulmonary manifestation is ac ute pneumonitis (0.3 and 11.6% of patients). It is more common in those with underlying lun g disease (including RA-ILD). It usually occurs within 2 years of starting therapy, but may occur after ces- sation of treatment. Diabetes, increased age and low albumin are all risk factors for acute pneumonitis. The clinical presentation is CASE 41 353 typically acute or subacute (weeks), and radiologically bilateral interstitial infiltrates or a combination of interstitial infiltrates and consolidation (as seen here) may occur. Corticosteroids. RA patients taking steroids are at greater risk of pneumonia requiring hos pitalization. Taking prednisolone at \211 10mg per day for a month is a small but signific ant risk factor for PCP. Anti-TNFa therapy. All anti-TNFa and other biologic therapies for RA (e.g. B cell depletors , anti-IL1 therapy) have been associated with increased risk of pulmonary infections. The c ommonest is an asso- ciation with bacterial pneumonia. There is also a well-known risk of t he development of active pulmonary tuberculosis after initiation of anti-TNFa therapies, an d screening is recommended prior to begin- ning such therapy (see British Thoracic Society website in Further reading). More recently, the use of anti-TNFa therapy has been associate d with exacerbations and an increased risk of mortality (see Ostor et al), although further evidence is needed. In this case, the clinical history and radiographic appearances make TB or other pulmonary infection alone unlikely. The time course of disease is very fast for RA-ILD alone. However , we are not given information on the patient \200\231s prior respiratory status (and she i s quite likely to have been limited by joint disease therefore a history of exercise tolera nce may be uninformative of her respiratory reserve) or exactly which drugs are being taken (i.e. is she still on methotrexate?). The two most likely pos- sibilities are methotrexate induced pnuemonitis or undiagnosed and asymptomatic RA-ILD (most likely UIP) with intercur rent infection. 41d) Describe two key initial investigations and their rationale. Important investigations include: \227\206 Pulmonary function tests \200\224these may aid in the diagnosis of RA-ILD (restri ctive PFTs, small lung volumes, decreased TLCO) or suggest COP (preserved volumes on CXR, d ecreased KCO). However, this patient may be too compromised to perform anything except simp le spirometry \227\206 HRCT chest \200\224this would enable assessment of the zonal predominance of the infiltrates (basal and subpleural implying UIP), the relative pres- ence of ground glass an d reticulation (NSIP or methotrexate pneumo- nitis versus UIP), consolidation (COP, intercu rrent infection, PCP) and lobar involvement (pneumonia) CASE HISTORIES IN RESPIRATORY MEDICINE 354 \227\206 Bronchoscopy, +/ \200\223 lavage, +/ \200\223 transbronchial biopsy. Exclusion of infection (lavage) before consideration of the other diagnoses is key, especially if the H RCT is not definitively RA-ILD and, as in this case, the history is short. Transbronchial b iopsy may be useful in the diagnosis of COP, and provides a modest increase in diagnostic y ield for PCP (around 10%) \200\224however, it is unlikely that this patient would tolerate a pneumothorax. \227\206 Consideration should be given to open lung biopsy if there is real diagnostic uncertainty after the above tests. Progress The patient was commenced on broad-spectrum antibiotic therapy, oxygen and thrombo-embolism prophylaxis and HRCT was performed ( Fig. 41.2 ). Fig. 41.2 HRCT chest. CASE 41 355 Questions 41e) Describe the HRCT findings. 41f) What is the most likely diagnosis and what treatment would you consider? CASE HISTORIES IN RESPIRATORY MEDICINE 356 Answers 41e) Describe the HRCT findings. There is widespread ground glass opacification, with a peripheral, subp- leural predominanc e ( Fig. 41.3 ). On the basal cuts, there is coarse reticu- lation with areas of traction b ronchiectasis (see Fig. 41.3 ). Fig. 41.3 Expanded HRCT chest. 41f) What is the most likely diagnosis and what treatment would you consider? The HRCT is suggestive of RA-ILD with coarse reticulation and traction dilatation of airway s (or \200\230bronchiectasis \200\231; implying a chronic fibrotic process, e.g. UIP). The ground glass opacity may represent an additional pathology (e.g. drug-induced lung disease , infection, inflammation such as NSIP) or established fibrosis, which is beyond the resolu tion of the CT scanner. Given the acute deterioration in the patient, the putative diag- no sis of RA-ILD (UIP) in association with methotrexate induced pneu- monitis was made. Treatment of methotrexate induced pneumonitis: \227\206 Immediate cessation of methotrexate \227\206 Patients will usually respond to this alone, but high-dose oral steroids are reco mmended to speed recovery if patients are acutely unwell (as here) CASE 41 357 \227\206 In general, methotrexate should be avoided in the future (although if no other th erapeutic options exist, slow re-introduction and careful monitoring of pulmonary function and CXR may be considered). Treatment of RA-ILD (UIP): \227\206 There are no large studies addressing the management of patients with RA-ILD and treatment is based on the associated idiopathic interstitial pneumonia (i.e. UIP). \227\206 NSIP and COP are, therefore, treated with oral steroids, as per the treatment of non-RA entities. \227\206 The treatment of RA-UIP is more controversial. There are many case reports of suc cessful treatment with a variety of anti-RA drugs, but all of these are associated with pos sible significant pulmonary toxicity. \227\206 One study has suggested that anti-TNF the rapy may slow progression of RA-ILD, but another has reported severe respiratory failure wi th this treatment. Further reading Gauhar UA , Gaffo AL , Alarc n GS ( 2007 ). Pulmonary manifestations of rheumatoid arthritis . Semin Respir Crit Care Med ; 28 ( 4 ): 430 \200\223 440. Kim DS ( 2006 ). Interstitial lung disease in rheumatoid arthritis: recent advances . Curr Opin Pulm Med ; 12 ( 5 ): 346 \200\223 353. Nannini C , Ryu JH , Matteson EL ( 2008 ). Lung disease in rheumatoid arthritis . Curr Opin Rheumatol ; 20 ( 3 ): 340 \200\223 346 . Ostor AJ, Crisp Aj, Somerville MF, Scott DG (2004). Fatal exacerbation of rheumatoid athrit is assoicated fibrosing alveolitis in patients given infliximab. BMJ ; 329 :1266. British T horacic Society Standards of Care Committee (2005). BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to anti-T NF- treatment. Thorax ; 60 : 800 \200\2235. Case 42