CASE HISTORIES IN RESPIRATORY MEDICINE 186 Following an acute reaction, the prognosis is good. Following chronic lung disease, drug wi thdrawal may lead to an improvement; however, mortality is still 10%. The role of corticost eroids in nitrofurantoin- induced lung disease has not been properly evaluated. \227\206 For the suspected UIP component of her disease, drug treatment is not used routin ely. Oral corticosteroids alone, or in combination with azathioprine, may improve lung func tion and survival, though studies supporting their use probably included some patients with pulmonary fibrosis other than UIP, such as non-specific interstitial pneumonitis, which is steroid responsive. Further progress Intra-venous amoxicillin and oral erythromycin were given for a community acquired pneumoni a. Her shortness of breath improved a little, and the CRP fell; inspiratory crackles and CX R changes persisted. A CT was performed ( Fig. 23.2 ). CASE 23 187 Fig. 23.2 CT chest. Questions 23c) Describe the CT chest changes. 23d) What further investigations could be considered? CASE HISTORIES IN RESPIRATORY MEDICINE 188 Answers 23c) Describe the CT chest changes. The CT shows ground glass opacification associated with traction dilata- tion and bronchiec tasis, and areas of coarse reticulation and honey- combing. In the upper zones on CT, chang es predominate on the right. Appearances would be in keeping with severe usual interstitial pneumo- nitis, although the asymmetrical distribution would be unusual. 23d) What further investigations could be considered? An open lung biopsy is sometimes helpful in cases of pulmonary fibrosis where there is doub t regarding the underlying diagnosis. Full pulmonary function tests aid assessment at seque ntial follow-up. This lady was not sufficiently stable to be considered for this. Early recognition of drug toxicity is important as it is a common cause of morbidity and ev en mortality. Unfortunately the lady in this case went on to develop progressive fibrosis a nd secondary pulmonary infection, and died 3 months after initial presentation. Further reading Jick SS , Jick H , Walker AM , Hunter JR ( 1989 ). Hospitalization for pulmonary reactions following nitrofurantoin use . Chest ; 96 : 512 \200\223 515 . Martin WJ ( 1991 ). Pharmacologic and other chemical causes of interstitial lung disease . Chest ; 100 : 231 \200\223 233 . Schattner A , Von der Walde J , Kozak N , Sokolovskaya N , Knobler H ( 1999 ). Nitrofurantoin-induced immune-mediated lung and liver disease . Am J Med Sci ; 317 ( 5 ): 3 36 \200\223 340 . Case 24 A 45-year-old engineer (born 1943) was referred by his GP for possible sleep apnoea in 1988 . His presenting complaint was increasing and severe daytime sleepiness (he had fallen asle ep whilst on the telephone and driving), general tiredness and fatigue, and restless sleep. He was known to be a snorer, but not every night. He had been a smoker for 25 years, havin g given up recently. He had had rheumatic fever aged 6 and a squint operation aged 8. Aged 16 he was 6ft 2in but by 17 he had lost 2in and was noticed to have a scoliosis. By aged 20 this was bad enough to require a spinal fusion. On examination he was 5ft 9in and thin (BM I 21). Apart from the scoliosis there was no evidence of a neuromuscular abnormality, in pa rticular no fasciculation; nor evidence of cor pulmonale. Investigations Formal sleep study (Fig. 24.3) showed that the episodes of worsening hypoxae- mia were duri ng REM sleep, and there was no evidence of obstructive sleep apnoea. Pulmonary junction (Table 24.1) and blood gasses (Table 24.2) were as follows. Table 24.1 Pulmonary function tests % Predicted PEFR(L/m) 375 75 FEV1(L) 1.6 48 FVC(L, standing) 2.2 53 FVC(L, lying) 2.1 51 FEV1/VC(%) 72 low normal FRC(L) 2.3 66 RV(L) 1.4 59 TLC(L) 3.6 53 RV/TLC(%) 38 33 RAW(kPa/L/s) 0.14 (<0.2) SGAW(L/s.kPa) 3.1 normal TLCO(mmol/min/kPa) 5.3 56 KCO(mmol/min/kPa/L) 1.70 115 PiMax(cmH2O) 33 low normal PeMax(cmH2O) 95 normal CASE HISTORIES IN RESPIRATORY MEDICINE 190 Table 24.2 Blood gasses PaO2(kPa) 6.81 SaO2(%) standard [HCO 3]- (mmol/l) Aa gradient (kPa) 88 PaCO2(kPa) 7.65 30.6 pH 7.34 3.6 Fig. 24.1 Chest radiograph. Fig. 24.2 Chest CT slice. CASE 24 191 Eight sequential hours of oximetry \200\223 each line 70 \200\223100% SaO2 Start of night 100 70 End of night 60 minutes Fig. 24.3 Eight sequential hours of oximetry taken from the sleep study. Questions 24a) What abnormalities do the lung function tests show? 24b) What abnormalities do the blood gasses show? 24c) Can the lung function tests explain the blood gasses? 24d) Does the CXR and CT slice help? 24e) Does the sleep study help? 24f) What general group of disorders are these abnormal findings likely to result from? CASE HISTORIES IN RESPIRATORY MEDICINE 192 Answers 24a) What abnormalities do the lung function tests show? Lung function shows a restrictive defect with no evidence of additional airways obstruction . Lung volume measurements are about 50% pre- dicted. The FEV 1 /VC ratio is slightly low; however, there is no evidence of air trapping (normal RV/TLC ratio), increased airways obst ruction or decreased conductance. The KCO is slightly raised, as one would expect if there was failure to expand otherwise relatively normal lung. The pre- served FVC on lying down e ssentially rules out diaphragm weakness. The expiratory mouth pressure is well preserved; t he inspiratory pres- sure is a little low, either due to weak muscles or mechanically disad van- taged muscles, as occurs in scoliosis. 24b) What abnormalities do the blood gasses show? The blood gasses show a partially compensated, mild ventilatory failure with a small increa se in Aa gradient. 24c) Can the lung function tests explain the blood gasses? Lung function and blood gasses. In patients with a scoliosis, the VC usu- ally has to fall to about a liter before ventilatory failure occurs. With neuromuscular causes of ventilator y failure, it has been shown that the lying VC is the most predictive of diurnal CO 2 reten tion, and usually needs to fall to below 25% predicted normal. Thus to be in ventilatory fa ilure with a lying VC over 2L would be very unusual, and requires addi- tional explanation. This might be obesity (but he is thin), additional airways obstruction (e.g. from his smok ing, but the lung function does not support significant airways obstruction) or a neuromusc ular cause of weakness (for which there is no obvious supporting evidence). 24d) Does the CXR and CT slice help? The CXR (Fig. 24.1) shows the expected scoliosis, with the vertebral sta- bilisation applie d to the lumbar area, rather than the thoracic. The CT slice (Fig. 24.2) shows areas of pro bable atelectasis from failure to ade- quately expand parts of the lung, the likely explana tion for the raised Aa gradient. 24e) Does the sleep study help? The sleep study (Fig. 24.3) shows a stable reduction in SaO 2 during non- REM sleep, and ye t further large unstable falls in SaO 2 during REM sleep, but none of the recurrent saw-too th oxygen desaturations typical of obstructive sleep apnoea. This would be typical of any v entilatory failure CASE 24 193 patient, from many different causes, e.g. neuromuscular, COPD, obesity and scoliosis, as he re. 24f) What general group of disorders are these abnormal findings likely to result from? The likely cause is not clear at all, and one is either looking at two unre- lated diagnose s (e.g. an additional brain stem abnormality such as Arnold Chiari malformation), or a rare neurological diagnosis that could cause both a central control abnormality and the late on set scoliosis. Questions 24g) Suggest a possible single neurological diagnosis. 24h) What additional tests might help confirm this diagnosis? CASE HISTORIES IN RESPIRATORY MEDICINE 194 Answers 24g) Suggest a possible single neurological diagnosis. Previous polio might explain the findings, but cannot be proven. 24h) What additional tests might help confirm this diagnosis? Electrophysiological studies might show evidence of previous denerva- tion and re-innervati on in multiple areas of the body. They, in fact, did show evidence of motor unit action pot entials increased in size and prolonged in duration, compared to normal (suggesting that su rviving anterior horn cells were innervating greater numbers of muscle fibers than normal). These changes were present in several areas. There were no fibrillation potentials to impl y ongoing motor axon loss. These find- ings were interpreted as showing widespread evidence of chronic motor neuron loss. This patient is now nearly 20 years on from the original pre sentation with ventilatory failure and he shows no evidence of increas- ing weakness. Poliomyelitis is caused by a highly infectious enterovirus that gains entry via the GI trac t, having been excreted in feces from an active case. It reproduces in the pharynx and GI t ract for 2 weeks or so, before being either contained, or producing a viraemia with signs o f meningeal irrita- tion. Even at this stage, only about two-thirds will go on to detectabl e paralysis. Over 90% of infections do not produce an episode of \200\230aseptic meningiti s \200\231 or muscle weakness, but are simply diagnosed as a pharyngi- tis or \200\230flu \200\231; evidence for this comes from epidemiological viral antibody studies. It is though t that over 50% of the anterior horn cells supplying a muscle need to be destroyed in the a cute phase to produce noticeable weakness. Recovery of weakness is due to re-innervation of orphaned muscle fibers. Scoliosis can develop after the original involvement of the parave rtebral muscles (due to unbalanced spinal support with bending away from the weaker affecte d side), usually during a subsequent growth spurt some while later. Electrophysiological st udies show that many muscle groups, not originally thought to have been involved, show evid ence of chronic denervation, indicating more widespread \200\230involve- ment \200\231 tha n symptomatically evident. In addition to involvement of ante- rior horn cells supplying pe ripheral muscles, there is clinical and post-mortem evidence of neuronal damage in other ar eas. For example, there is a bulbar form that can involve the brainstem areas controlling a utonomic function, pharyngeal function and ventilatory control. Such cases tended to be sev ere and patients rarely survive without ventilatory CASE 24 195 Fig. 24.4 Superimposed medullary lesions (dashed black lines) from 17 patients who died of ventilatory failure secondary to bulbar poliomyelitis. Located in the lateral reticular for mation. From Baker et al. (1950). Arch Neurol Psychiat; 63: 257 \200\223281. support. Figure 24.4 shows the areas in the brainstem that need to be destroyed by poliovir us to produce acute ventilatory failure. Many years after the original polio (usually 20 \200\22340 years later), there can be an in crease or return of weakness in areas previously affected; this has been termed \200\230po st-polio syndrome \200\231. The mechanism of this is not clear. Suggestions that it is due to persisting virus and new anterior horn cell damage, have no real supporting evidence. Jo ints that suffered from loss of some muscle support, and thus mechanical imbalance, can be gradually damaged over time, with the resulting osteoarthritis producing new disability. Th e favored explanation is that the surviving anterior horn cells originally sprouted new bra nches to re-innervate the orphaned muscle fibers and that, after many years, they premature ly age due to the \200\230over-use \200\231 of having to supply more muscle fibers. There is evidence of increased fatigability of muscles from polio survivors, which may explain th e complaint of excess fatigue typical of this syn- drome. In addition, there can be apparen tly inexplicable problems, such as dysphagia, autonomic dysfunction and ventilatory failure . The pre- dictors of late ventilatory failure are respiratory muscle involvement (with a p eriod on a ventilator) during the original polio, and the pres- ence of significant scolios is. Further subsequent decline is usually very slow. Modafinil does not help the fatigue. T here is early evidence that intravenous immunoglobulin may improve symptoms; if true, then there may be alternative explanations for the syndrome, besides those suggested above. CASE HISTORIES IN RESPIRATORY MEDICINE 196 To diagnose post-polio syndrome requires (Farbu et al . 2006): \227\206 A history of paralytic polio; confirmed or not confirmed; partial or fairly complete initial recovery. \227\206 After a period of functional stability of at least 15 years, development of new m uscle dysfunction: muscle weakness, muscle atrophy, muscle pain and fatigue. \227\206 Neurological examination compatible with prior polio: lower motor neuron lesions; decreased or absent tendon reflexes; no sensory loss; compatible findings on EMG and/or MR I. Thus this patient does not have the full house to allow a diagnosis of post-polio syndrome; the vast majority of such patients do have a clear history of previous polio. However, it is possible that he contracted apparently asymptomatic polio in his early teens (during the polio epi- demics of the 1950s), which involved his thoracic paravertebral muscles, mainly on the right, and perhaps with partial bulbar damage as well. During his adolescent growth spurt a scoliosis subsequently developed. Some 35 years later, the combination of the scol iosis and possible partial bulbar damage led to mild ventilatory failure with marked noctur nal hypoventilation, particularly during REM sleep when compensatory ventilatory mechanisms are least effective due to the muscle paralysis accompanying normal REM sleep. Progress This patient was placed on non-invasive ventilation overnight with normaliza- tion of both his sleep study (Fig. 24.5) and PaCO 2 (PaO 2 9.7, PaCO 2 5.6, base excess \200\2231.5). H e has remained well for nearly 20 years and his FVC is stable at 2L; this would further sup port a diagnosis of post-polio effects, rather than any alternative progressive neuro-muscu lar disorder. If he tries not to use his ventilator at night, his sleep is again disrupted, and by the fourth night his PaCO2 is again abnormally raised. CASE 24 197 Eight sequential hours of oximetry \200\223 each line 70 \200\223100% SaO2 Start of night 100 70 End of night 60 minutes Fig. 24.5 Eight sequential hours of oximetry taken from the sleep study. Further reading Bach JR ( 1995 ). Management of post-polio respiratory sequelae . Ann N Y Acad Sci ; 753 : 96 \200\223 102 . Farbu E, Gilhus NE, Barnes MP, Borg K, deVisser M, Driessen A et al . ( 2006 ). EFNS guide- line on diagnosis and management of post-polio syndrome . European Journal of Neurology ; 1 3 : 795 \200\223 801 . Howard RS ( 2005 ). Poliomyelitis and the postpolio syndrome . BMJ ; 330 : 1314 \200\223 1 318 . Case 25 A 40-year-old woman presented to A&E with pleuritic right-sided chest pain. This had occurr ed suddenly whilst at rest, and was associated with shallow breathing. She had a past histo ry of dysmenorrhoea, investigated with a lapar- oscopy with no positive findings two years previously, but was otherwise fit and well. She was currently on day three of her period. S he was a lifelong non-smoker, with two healthy children. On examination, she was tachypnoei c (20/min) with oxygen saturations of 96% on air, and decreased breath sounds on the right side. Her CXR is shown in Fig. 25.1. Fig. 25.1 CXR. Questions 25a) What is the diagnosis? 25b) How would you quantify its size? 25c) What is the relevance of size to treatment? 25d) How would you treat this patient and why? 25e) What is the prognosis from this condition? 25f) What counseling does she require on discharge? CASE HISTORIES IN RESPIRATORY MEDICINE 200 Answers 25a) What is the diagnosis? The diagnosis at this stage is of primary, spontaneous pneumothorax (PSP). Although the his tory of previous dysmenorhoea is of interest, after a first episode of pneumothorax a diagn osis of catamenial pneu- mothorax (related to the menstrual cycle) cannot be made confident ly. This diagnosis requires recurrent pneumothoraces within 72h before or after the onset o f menstruation. The presence of endothoracic endometrial tissue is not required for a diagn osis. 25b) How would you quantify its size? There are several ways in which to score the size of a pneumothorax, recommended in managem ent guidelines. All take into account that estimation of a volume change on a two-dimension al image (i.e. the CXR) is inaccurate. Some authors have suggested a simple classification scoring pneumothorax into \200\230large \200\231 (complete dehiscence of the lung from the chest wall, as seen here, Fig. 25.2) and \200\230small or moderate \200\231 (partial dehi scence). American and British guidelines (see reading list) recommend different cut-offs fo r size of pneumothorax: >2cm rim large (UK) or >3cm rim large (USA). While there are comple x research tools available to calculate the degree of lung collapse, a reasonable clinical tool is the \200\230Light index \200\231. This approximates pneumothorax size using the cu be of the lung diameter to hemithorax diameter (see Fig. 25.2 ). 25c) What is the relevance of size to treatment? Etiology and clinical status of the patient determines which treatment strategy to use, rat her than precise calculations of pneumothorax volume. (Hemithorax d3 \210\222 lung d3) / Hemithorax d3 (103-73) / 103 = 66% pneumothorax Fig. 25.2 CXR showing calculation of the Light index, which has been shown to closely corre late with the amount of air obtained at aspiration. CASE 25 201 This is especially important in patients with secondary pneumothorax (i.e. in the presence of underlying lung disease), where the lung may not collapse due to air trapping in the und erlying lung, or be tethered, giving the appearance of a small pneumothorax on PA CXR. In s econdary pneu- mothorax, even small pneumothoraces can cause significant symptoms and \200 \230tension \200\231. Intervention is recommended in patients with \200\230large \200\231 pneu- mothoraces in guidelines, but the clinical state of the patient should be the first a ssessment tool and trump the guidelines. In the presence of com- plete pneumothorax (total lung collapse), aspiration or drainage is likely to be required due to symptoms and the the oretical risk of tensioning. 25d) How would you treat this patient and why? Possible treatment strategies in first episode of PSP are shown in Table 25.1 . If sufficiently symptomatic, the likely best treatment strategy in this case is aspiration (on the basis of no difference in outcomes listed in Table 25.1 and potentially decreased r isks). There is a large pneumothorax on radio- logy in association with symptoms, requiring intervention, with a high pos- sible success rate from aspiration, which may avoid the nee d for admission. Drain placement is associated with significant potential risks and should be considered carefully before being used as a treatment for this disease. 25e) What is the prognosis from this condition? As above, the prognosis of PSP is good, and it should be regarded as an inconvenient but be nign disease (mortality 0.09% in men, 0.06% in women). This is in contrast to secondary pne umothorax (in the presence of underlying lung disease) which is associated with a 10 \200 \22315% mortality. Recurrence rates after a first episode PSP are between 16 and 57%, with a mean of 30%, and most occur within 2 years of initial event. Smoking cessation is a key c omponent to management, as recurrence is up to 9 times more likely in continuing smokers. 25f) What counseling does she require on discharge? Post-PSP resolution, patients should be advised to stop smoking, if relevant, and advised a bout flying and diving. Patients who have experi- enced even a single PSP may not dive with pressurized breathing equip- ment (snorkling is considered safe) unless a surgical pleurod esis has been conducted. Previous guidelines suggested patients should wait for at least 6 weeks before flying after radiological resolution has occurred, but more recent guidelines suggest that patients may safely fly after 1 week of radiological resolution. Patients with active pneumothoraces may not fly (pneumothorax air expansion causing respiratory compromi se at lower CASE HISTORIES IN RESPIRATORY MEDICINE 202 Table 25.1 Pneumothorax management Management Evidence Conservative (no intervention, early follow up with CXR) PSP is a benign disease with <0.1% mortality or tension. Spontaneous resolution of pneumoth orax volume occurs at 1 \200\2232% of hemithorax volume per day. Must ensure no evidence of progression (i.e. no ongoing air leak). Aspiration (Aspiration may be conducted using an intravenous cannula system or specially de signed catheter aspiration kits. These kits consist of an 8F catheter passed in to the ches t over a guide-wire with a 3-way tap. The success of initial aspiration may be checked with radiology without removing the catheter, and re-aspiration conducted, if required.) Aspiration successful in 59 \200\22373% of PSP in five randomized trials comparing aspirati on to intercostal drainage. Cochrane review of trials (including only one study) showed no difference between drainage and aspiration in: Immediate success rate \227\217 Early (1-month) failure rate \227\217 Duration of hospita l stay \227\217 Need for pleurodesis at 1 year \227\217 Decreased number of admissions wi th aspiration. Pilot studies suggest good success rates from aspiration kits. In PSP, incre ased size of pneumothorax is associated with increased likelihood of treatment failure. Intercostal Drainage Good success rates and permits assessment of ongoing air leak (drain can be left in for sev eral days). Requires admission and associated with an up to 5% infection (empyema) rate. Pl eurodesis may be conducted through an intercostal drain on resolution of pneumothorax, but this is not recommended in PSP (although widely practiced in Europe). Thoracic Surgery Highly successful in treatment and prevention (around 95% for thoracotomy, somewhat lower f or mini- thoracotomy and video-assisted thoracoscopic surgery (VATs)). Two studies demonstr ating cost saving using VATs as initial treatment for first episode and recurrent pneumotho rax. Mean recurrence rate in PSP after one episode is 30%; therefore, 70% of patients will not require further treatment after the 1 st episode. Surgery therefore not recommended aft er first episode. pressures). Once full resolution has occurred clinically and radiologi- cally, the theoreti cal risk of flying is of a recurrence occurring at altitude. As this may occur in 30% of pa tients (i.e. the minority) over a 2-year period, a pragmatic approach has now been taken. Progress The patient was successfully treated with a single aspiration, with good radio- logical res ult. She was counseled and discharged and at follow-up 1 month later was well, although rem ained anxious about possible recurrence. CASE 25 203 Fig. 25.3 Apical slices from thoracic CT. She represented 4 months later with the same symptoms (not during men- struation), and was found to have a moderate right pneumothorax. She refused further aspiration or chest drain insertion, and requested surgical intervention. A CT ( Fig. 25.3 ) scan was therefore perfo rmed. Questions 25g) What does the CT show (Fig. 25.3)? 25h) Does the CT inform etiology or treatment options? 25i) What are the surgical options available? CASE HISTORIES IN RESPIRATORY MEDICINE 204 Answers 25g) What does the CT show (Fig. 25.3)? The CT ( Fig. 25.3 ) shows a current right-sided pneumothorax and small subpleural blebs an d bullae (arrows) collectively known as emphysema- like changes (ELCs) (Fig. 25.4). Fig. 25.4 Expanded chest CT. 25h) Does the CT inform etiology or treatment options? Treatment options. After a second PSP, recurrence rates are higher (around 50%) and decisio ns of medical management versus surgical treatment are largely dependent on patient choice. In the case of a third episode ipsilat- erally, ongoing air leak or first evidence of bila teral pneumothorax (usu- ally on separate occasions), surgical intervention is recommended. The decision to operate is not usually based on CT appearances. Etiology of PSP. The etiology of PSP is unknown. ELCs may be the areas of parenchymal air l eak in PSP, and are found in 90% of cases at thoracotomy and 80% of cases using HRCT in bot h smokers and non- smokers with PSP, in comparison to 25% of matched controls without PSP. PSP patients are taller than average, and it is postulated that the increased gradient in p leural pressure may lead to bleb and bulla forma- tion and result in PSP. However, ELCs hav e not been convincingly shown to predict first or recurrent pneumothorax. CASE 25 205 Direct evidence from thoracotomy suggests that observed air leak from ELCs is highly variab le (between 4 and 75% of cases). Studies have dem- onstrated that recurrence rate is higher in patients treated with bullec- tomy alone compared to bullectomy plus pleurodesis, argui ng against all PSP being a result of ELC leakage. Interesting data, using inhaled fluor- os cein to assess the site of air leak at thoracoscopy, suggest that areas not associated with visible bullae are often responsible. Resected specimens from pneumothorax lungs demonstra te small airways inflammation almost universally, suggesting that the pathology may be more widespread within the lung parenchyma. The CT appearances, therefore, do not change the treatment options in this case, although m ost thoracic surgeons would conduct a pleurodesis and blebectomy in this situation. Further studies are required to assess the validity of this approach. 25i) What are the surgical options available? Surgical options: \227\206 Open thoracotomy \200\224demonstrates the best results, usually pleurec- tomy per formed during the procedure. A pneumothorax recurrence rate of around 1% is quoted. However , chronic post-thoracotomy pain is common, occurring in 75% of patients at 6 months and 61% one year after surgery. \227\206 Mini-thoracotomy \200\224less invasive than above (5cm axillary scar) and a recurrence rate comparable to open thoracotomy is reported. \227\206 Video-assisted thoracoscopic surgery \200\224even less invasive but with a reported recurrence rate of 5 \200\22310%. Further reading Baumann MH , Noppen M ( 2004 ). Pneumothorax . Respirology ; 9 : 157 \200\223 164 . Bauman n MH , Strange C , Heffner JE et al . ( 2001 ). Management of spontaneous pneumothorax: an American College of Chest Physicians Delphi consensus statement . Chest ; 119 : 590 \200\223 602 . Henry M , Arnold T , Harvey J ( 2003 ). BTS guidelines for the management of spontaneous pneumothorax . Thorax ; 58 Suppl 2 : ii39 \200\223 ii52 . Case 26 A 70-year-old man was admitted with severe dyspnoea, paroxysmal nocturnal dyspnoea and an u nproductive cough that had progressed over 4 days. He gave a background history of minor ex ertional breathlessness over the last 6 months. A CXR 3 months previously had raised concer n over a pulmonary nodule, and this had prompted a CT confirming multiple subpleural nodule s, up to 16mm in size, along with borderline enlargement of mediastinal and axillary lymph nodes. An interval CT to assess any change was awaited at the time of his acute presentatio n. His background was of Type II diabetes mellitus (15 years dura- tion), hypertension and mild chronic renal failure (recent urea 8.0mmol/L, and creatinine 151 mol/L). Systemic enq uiry revealed intermittent nasal blockage, discharge and crusting. On examination he had a sinus tachycardia of 115, respiratory rate of 25/min, Sa O 2 of 26% on Fi O 2 0.6 and BP 10 5/70. JVP was not seen and there was peripheral oedema to both knees. Heart sounds were nor mal, and chest examination revealed reduced air entry at both bases and fine crackles to bo th upper zones. Investigations \227\206 Arterial blood gas (on 60% O 2 ): PaO 2 9.7kPa, PaCO 2 4.5kPa, pH 7.42, [HCO3 ] 26 mmol/L \227\206 Urinalysis, + protein, trace non-haemolysed blood \227\206 Urea 16.2mmol/L, creatinine 202 mol/L, LFT normal, CRP 64mg/L, ESR 37mm/h \227\206 Hb 8.4g/dL (previous Hb 8.9), MCV 85fl, WCC 11.3 \227 10 9 /L (eosi- nophils 0.45 \227 10 9 /L), Plts 445 \227 10 9 /L \227\206 Serum ferritin 201.8ng/mL (20 \200\223300), iron 15.0 mol/L (14 \200\22331), tra ns- ferrin 1.97g/L (1.8 \200\2233.6), B12/folate normal; blood movie showed nor- mochromic, normocytic red cells. CASE 26 207 Fig. 26.1 CXR. Questions 26a) Interpret the CXR (Fig. 26.1). 26b) What is the most likely diagnosis and underlying cause for his acute presentation? 26c) What other diagnoses should be considered? 26d) What further investigation should be done? CASE HISTORIES IN RESPIRATORY MEDICINE 208 Answers 26a) Interpret the CXR (Fig. 26.1). The CXR ( Fig. 26.1 ) shows that the heart is enlarged. There is bilateral perihilar and lo wer zone consolidation with airspace opacification extending to the apices. There are bilat eral effusions. 26b) What is the most likely diagnosis and underlying cause for his acute presentation? The most likely diagnosis is acute pulmonary oedema, although the CXR is not entirely typic al. With his risk-factor profile, coronary artery dis- ease would be the most likely underl ying cause for this. Additional issues that require explanation are the deteriorating renal function and anae- mia. A possible cause for this would be progressive diabetic nephropath y with an anemia of chronic disease. It would, however, be unusual for erythropoietin defic iency to cause anemia at this level of renal dysfunction, and iron studies are difficult to interpret in acute illness. 26c) What other diagnoses should be considered? Other causes of diffuse pulmonary infiltrates should be considered such as infection, adult respiratory distress syndrome (ARDS), other inflamma- tory processes (e.g. organizing pneu monia, acute interstitial pneumonitis), vasculitis or pulmonary hemorrhage. 26d) What further investigation should be done? Further investigations would include: \227\206 Cardiac troponin and echo \227\206 Blood and urine cultures \227\206 Spot urine protein/creatinine ratio (PCR) \227\206 Urine microscopy for casts \227\206 ANCA \227\206 Renal ultrasound \227\206 Consider CT chest and pulmonary function tests, if no improvement with initial therapy. Progress Further investigations \227\206 Cardiac troponin negative. \227\206 Echo showed normal left and right ventricular systolic function and no valvular a bnormalities. There was no suggestion of diastolic dys- function, nor evidence of pulmonary hypertension. CASE 26 209 \227\206 Urine protein/creatinine ratio 120mg/mmol (levels over 300mg/mmol generally considered nephrotic). \227\206 Urine microscopy negative for red cell casts. \227\206 c-ANCA positive at 1/40 titre, anti-PR3 43.7U/mL(0 \200\2236), anti-MPO 21.1U/mL(0 \200\2236). \227\206 Renal ultrasound normal. Following an initial bolus of 50mg furosemide and 2 days treatment with 40mg furosemide onc e daily, the patient remained dyspnoeic and hypoxic with no improvement in his CXR appearan ces. Hemoglobin levels did not change significantly and there was no growth on urine or blo od cultures. The patient was too unwell to perform reliable pulmonary function tests. A CT scan was performed ( Fig. 26.2 ). Fig. 26.2 CT thorax. Questions 26e) Interpret the CT scan (Fig. 26.2). 26f) What diagnosis are the appearances most consistent with? CASE HISTORIES IN RESPIRATORY MEDICINE 210 Answers 26e) Interpret the CT scan (Fig. 26.2). The CT (Fig. 26.2) shows an enlarged heart, bilateral pleural effusions, bilateral ground g lass opacification in a predominantly central and upper zone distribution. There are areas of peripheral consolidation. There is also interlobar septal thickening ( Fig. 26.3 ), whic h is not irregular or nodular. The lymphadenopathy identified on the initial CT (not shown) had not changed significantly but the parenchymal changes were obscuring the previously id entified nodules and so it was not possible to comment on any interval changes to them. Interlobar septal thickening Fig. 26.3 Selected CT section. Interlobar septal thickening is commonly caused by fluid, where the thickening is smooth, o r malignant infiltration of lymphatics (lym- phangitis), where it is more nodular. It can a lso be a finding in interstitial fibrosis (irregular septal thickening) and rarely in bronc hiectasis. 26f) What diagnosis are the appearances most consistent with? Despite the previously normal echo, these appearances are most consistent with ongoing pulm onary oedema. The positive ANCA raised concerns of vasculitis, and hence pulmonary hemorrha ge should be considered. The CT appearances are not those of vasculitis or pulmonary haemor - rhage, and the lack of any change in hemoglobin would also go against pulmonary hemorrhag e. There is often wide inter-observer variation in the reporting of left ventricular systolic function (LVSF) on USS, but even if LVSF appears normal, diastolic dysfunction (especially in hypertensive patients) alone can cause clinically evident heart failure. CASE 26 211 Progress More aggressive diuretic treatment was commenced, which did improve the situation symptomat ically and radiologically. A repeat cardiac USS was performed, which was again reported as normal. Subsequently, renal artery stenosis (unilateral, left-sided) was demonstrated by MR angiography. The renal team advised that this would not have been a cause for his pulmonar y oedema, as it was unilateral and not an especially tight stenosis; therefore, no further intervention for this was recommended. In addition, a myocardial perfusion scan showed no e vidence of regional ischaemia. The precise cause of his pulmonary oedema remained unclear a nd the cardiologists did not recommend coronary angiography. Repeat C-ANCA titre remained 1 /40 with Anti-PR3 of 123U/mL and creatinine remained around 200 mol/L. The renal team suggested that diabetic nephropathy, and not renal vasculi- tis, was respons ible for the chronic renal impairment. A renal biopsy was not felt to be necessary at this point. At chest clinic review 2 months later he had a residual cough and reduced exercise toleranc e with dyspnoea at 200 yards. Clinical examination revealed no evidence of cardiac decompen sation and a clear chest. CASE HISTORIES IN RESPIRATORY MEDICINE 212 Fig. 26.4 CXR at chest clinic review. CASE 26 213 Fig. 26.5 Interval CT thorax. Questions 26g) Interpret the CXR (Fig. 26.4) and CT (Fig. 26.5). 26h) What is the next investigation? CASE HISTORIES IN RESPIRATORY MEDICINE 214 Answers 26g) Interpret the CXR (Fig. 26.4) and CT (Fig. 26.5). The most striking abnormality shown on the CXR (Fig. 26.4) and the CT (Fig. 26.5) is the de velopment of a fairly rounded opacity in the left- upper zone, which may be pleurally based . There is also some persisting atelectasis in the right-lower zone. Although the heart app ears enlarged, there does not appear to be any persisting pulmonary oedema. The CT (Fig. 26.5) also shows bilateral spiculated nodules of varying size, with evidence o f cavitation in the right-lower lobe nodule. In addition, there is an area of consolidation anteriorly in the RLL. There is right par- atracheal lymphadenopathy. 26h) What is the next investigation? Core biopsy of left-upper lobe lesion would be the best next investigation, although a nasa l mucosal biopsy might have helped. The differential diagnosis is of Wegener \200\231s granulomatosis, organizing pneumonia and multi-focal intra-thoracic malignancy (including lym- phoma). Eosinophilc pneumonia should be considered, but would be discounted by lack of peripheral eosinophilia. Core biopsy of the lung lesion is, therefore, required to differentiate these. Although the right paratrac heal node would be amenable to tansbronchial needle aspiration, the only diagnosis this cou ld realistically secure would be of carcinoma. Core biopsy was performed. Tissue obtained showed patchy chronic inflammation including epi thelioid macrophages. No well formed gran- ulomas were seen nor tissue necrosis. No vasculi tis was observed. CASE 26 215 Questions 26i) What final investigation is required? 26j) What is your diagnosis? 26k) What drug treatment would you commence? CASE HISTORIES IN RESPIRATORY MEDICINE 216 Answers 26i) What final investigation is required? Renal biopsy. This is required to determine therapeut ic strategy (see below). Histology of this showed no evidence of renal vasculitis, but esta blished diabetic nephropathy only. 26j) What is your diagnosis? Non-renal Wegener \200\231s granulomatosis. Despite the lung biopsy not con- firming pathol ogically evident vasculitis, results so far are in keeping with a systemic vasculitis invol ving the upper (nasal symptoms initially described) and lower respiratory tract. 26k) What drug treatment would you commence? The management will be in two phases, namely induction and mainte- nance of remission. Prev ious conventional treatment of ANCA-associated systemic vasculitis would be combined cyclop hosphamide and high- dose prednisolone for induction, with cyclophosphamide continued for a t least one year and prednisolone gradually tapered over this time. This leads to remission in about 90% of cases. Concern regarding toxicity of cyclophosphamide (bone-marrow toxicit y, infection, myeloproliferative diseases) has led to recent studies addressing alternative , potentially less toxic treatment regimens. Recent evidence has suggested that in patients with systemic ANCA- associated vasculitis (W egener \200\231s or microscopic polyangiitis), but with- out life-threatening features (inc luding severe haemoptysis with bilateral infiltrates) or significantly impaired renal funct ion (creatinine >150 mol/L), induction of remission can just as effectively be achieved wi th methotrexate (MTX) as with cyclophosphamide (CYC) (de Groot et al . 2005). In this study , patients received either 15mg/week MTX ( n = 49) increasing to maximum 20 \200\22325mg/we ek by 12 weeks for a total of 12 months, or 2mg/kg/day CYC ( n =46) for 3 \200\2236 months. At remission, CYC was reduced to 1.5mg/kg/day until month 10, when it was tapered and stop ped by 12 months. Both groups received prednisolone 1mg/kg/ day for 12 weeks, then tapered to 15mg/day at 12 weeks, 7.5mg/day at 6 months and stopped at 12 months. Most (89) had Wege ner \200\231s and about half in each arm had lung involvement. At 6 months, the remission r ate in the MTX group (44/49, 89.8%) was not statistically significantly less than the rate in the CYC group (43/46, 93.5%). Time to remission with MTX was longer in the subgroup with respiratory tract involvement (nodules and/or cavities and/or pulmonary infiltrates). Rela pse rates at CASE 26 217 18 months of 69.5 and 46.5% in MTX and CYC groups, respectively, suggests treatment should be continued beyond 12 months.