Fibrosis Consolidation Bronchiectasis Fig. 35.3 Expanded portion of HRCT from Fig. 35.2. 35f) What diagnosis or diagnoses do they support? The diagnoses supported by this HRCT scan are of bronchiectasis in addition to a cause of m ulti-focal consolidation. The differential diagnosis in this context must include typical a nd atypical infections (including mycobacterial and fungal disease), lymphoid interstitial pneumonia, pulmonary lymphoma and drug reactions. 35g) How would you investigate and manage this patient? Bronchiectasis. The bronchiectasis is likely to have been caused by recur- rent infections in the past due to CVID (inadequate host defense in the bronchial tree). The patient \200 \231s clinical condition has deteriorated in the context of a positive sputum culture (PsA) and in this context, this should probably be treated with a view to microbiological eradic ation (4 \200\2236 weeks of oral ciprofloxacin with inhaled antibiotic). Some authori- ties would argue for an even more aggressive treatment strategy, as this is the first isolate o f PsA and the patient was unwell (i.e. single or dual intravenous treatment to achieve erad ication). CASE 35 299 Chronic infection with Pseudomonas is seen in up to one-third of patients with bronchiectas is, and has been associated with poorer lung function, decreased quality of life and more f requent hospital admissions. The cor- rect treatment paradigm in non-CF bronchiectasis is d ebated, with ran- domized evidence demonstrating good bacterial clearance using a combinati on of oral ciprofloxacin plus inhaled tobramycin for 14 days. However, this improvement in microbiology was not found to be associ- ated with clinical improvement, and in fact a wors ening of lung function was observed in these patients (presumably a reflection of airway re sponse to inhaled therapy). Extrapolating data from the CF population, most clinicians woul d attempt eradication of Pseudomonas in non-CF bron- chiectasis after the first isolate, al though direct evidence is lacking. BTS guidelines on this subject are due to be published i n 2009. Further well-established treatments for bronchiectasis include chest physiotherapy, patient education, microbiology directed antibiotics for exacerbations and vaccination (see case 1 ). In this case, vaccination is not useful as the patient has hypogammaglobulinaemia. Norma l investi- gation of additional causes of bronchiectasis may be equally limited in this cas e (e.g. Aspergillus precipitins). Other investigations Further investigation is required to clarify the abnormalities seen on the HRCT scan (nodul arity, infiltrates), especially if they do not clear after treat- ment for the infection. B ronchoalveolar lavage is an important investigation to exclude atypical infection (e.g. fun gi, non-tuberculous mycobacteria) and malignancy. Progress The patient underwent eradication therapy for Pseudomonas (oral cipro- floxacin and nebuliz ed colomycin for 4 weeks) with subsequent negative spu- tum cultures. The CXR abnormalities persisted, and she continued to complain of shortness of breath and malaise. Bronchoalveol ar lavage was conducted, showing no evidence of infection or malignancy, with increased num bers of lymphocytes and negative for microbiology including AFBs. A repeat CT scan 2 months later (not shown) showed increase in the infiltrate and nodularity. Question 35h) What is the differential diagnosis for these persistent CT changes and how would you proceed? CASE HISTORIES IN RESPIRATORY MEDICINE 300 Answer 35h) What is the differential diagnosis for these persistent CT changes and how would you proceed? The differential diagnosis radiologically includes lymphoid interstitial pneumonia (LIP), p rimary lymphoma of the lung and non-tuberculous mycobacteria. The negative lavage makes non -tuberculous mycobacteria highly unlikely. LIP is not bronchocentric in nature, and therefore transbronchial biopsies are unlikely to be helpful, and produce too small a sample to assess for lymphoma (transbronchial biopsies may be useful in this context as an aid to the diagnosis of atypical infection, but will no t help to achieve one of the diagnoses above). An open lung biopsy is, therefore, reasonabl e, to enable firm diagnosis, treatment and prognostication. CASE 35 301 Progress She underwent open lung biopsy, histology of which showed an interstitial infiltrate of lym phocytes and plasma cells along the alveolar septae, with no evidence of clonality. Questions 35i) What is the diagnosis? 35j) How would you manage this condition? 35k) What diseases is it associated with? CASE HISTORIES IN RESPIRATORY MEDICINE 302 Answers 35i) What is the diagnosis? The histology is consistent with a diagnosis of lymphoid interstitial. pneumonia (LIP). The disease is defined as a dense interstitial lymphoid infiltrate (including lymphocytes, pla sma cells, histiocytes) with exten- sive infiltration of the alveolar septae. There are lym phoid follicles and lymphoid hyperplasia present within the pulmonary lymphatics and non-ca seating granulomas may be seen. Lymphoid interstitial pneumonia is an uncommon disease classified within the idiopathic int erstitial pneumonias. It most commonly affects female patients in the fifth decade, and usu ally presents insidiously with increasing cough and breathlessness over a period of years. LIP is usually associated with another disease (see answer 35k). \227\206 Radiological features. LIP may present in a wide variety of radiological patterns . Two main CXR patterns have been described: basal intersti- tial changes associated with a ir space shadowing, and diffuse airspace involvement associated with honeycombing. On CT, g round glass shadowing is usually seen and may be associated with peri-vascular honeycombing or cyst formation. Multi-focal nodularity +/ \200\223 consoli- dation and reticulation may also be seen. \227\206 Diagnosis is made on the basis of clinical suspicion (especially in the presence of associated disease states as below) plus histology. The radiological features of LIP may occur in many infective/inflamma- tory diseases, and therefore histological proof is usual ly sought. The main differential diagnosis (once infection has been excluded) is of pulmona ry lymphoma, in which case a clonal population of lym- phocytes is seen, and there may be e vidence of tumor tracking along the lymphatics. Whereas LIP was previously considered to be a pre-malignant condi- tion that inevitably dev eloped in to lymphoma, only a small number of cases have been shown to follow this pattern and the majority of cases should be considered to be non-malignant. 35j) How would you manage this condition? Oral corticosteroids are the usual form of treatment, with radiological monitoring of respo nse, although there are no trials on which to base practice in this rare disease. Authoriti es recommend a prednisolone dose of 0.75 \200\2231mg/kg bodyweight for 8 to 12 weeks initia lly, followed by CASE 35 303 an attempt to reduce dose. Cases may resolve spontaneously, although around one-third progr ess to diffuse lung fibrosis. In this case, steroid treatment resulted in a dramatic clinic al and radiological improvement. Over the following 2-year period, high doses of steroids w ere required, however, and were associated with significant complications. Prognosis and required length of therapy is unknown. In around one- third of patients, prog ression occurs associated with poor prognosis, resulting in death in a median of 20 months. 35k) What diseases is it associated with? Associated conditions: \227\206 Auto-immune conditions, e.g. rheumatoid arthritis, SLE, haemolytic anemia, myasthenia, pernicious anemia, thyroid disease \227\206 Sj gren \200\231s syndrome (one-fourth of cases of LIP are reported to be associated with Sj gren \200\231s) \227\206 Immunodeficiency \200\224as seen here, e.g. in HIV, inherited conditions \227\206 Drug-induced (captopril and phenytoin) \227\206 Infections (e.g. Epstein Barr virus, pneumocystis pneumonia, hepati- tis B). Further reading Demedts M , Costabel U ( 2002 ). ATS/ERS international multidisciplinary consensus classification of the idiopathic interstitial pneumonias . Eur Respir J ; 19 ( 5 ): 794 \200\223 796 . Swigris JJ , Berry GJ , Raffin TA , Kuschner WG ( 2002 ). Lymphoid interstit ial pneumonia: a narrative review . Chest ; 122 ( 6 ): 2150 \200\223 2164 . Case 36 A 74-year-old woman was referred to the chest clinic with a 4-month history of malaise, cou gh, sputum production and an abnormal CXR. She had been treated with several courses of dif ferent antibiotics by her GP with some symp- tomatic response over that period. She had a p ast history of left breast carci- noma 20 years previously, treated with local resection an d high-dose radiotherapy. The patient reported significant skin damage after radiotherapy, and CXRs from 15 years previously, reviewed in the clinic, showed evidence of early left-up per zone fibrosis and mild volume loss. She was a life-long non-smoker with no other risk factors for respiratory disease. Her past medical history was otherwise unremarkable. On examination, chest expansion was decreased on the left, and the trachea was deviated to the left. There were crackles, and areas of bronchial breathing within the left-upper zone, respiratory rate was 16, and oxygen saturation was 92% on room air. There was no clubbing or lymphadenopathy. Investigations \227\206 Mildly raised inflammatory markers (ESR 36mm/h, CRP 62mg/L) \227\206 Normocytic anemia (Hb = 9.8g/dL, MCV = 74fL). \227\206 CXR in Fig. 36.1 and CT in Fig. 36.2. Fig. 36.1 CXR. CASE 36 305 She proceeded to CT scanning of the chest, for which images of the right lung are shown onl y ( Fig. 36.2 ). Fig. 36.2 CT scans. Questions 36a) Describe the CXR (Fig. 36.1 ). 36b) Describe the chest CT findings (Fig. 36.2 ) 36c) Suggest a possible differential diagnosis for this presentation. 36d) What investigations would you arrange? CASE HISTORIES IN RESPIRATORY MEDICINE 306 Answers 36a) Describe the CXR (Fig. 36.1 ). The CXR shows volume loss in the left lung (raised hemidiaphragm, rib crowding, hilar displ acement, ipsilateral tracheal shift) in association with areas of reticulation and linear a telectasis. In addition, a fluid level is apparent. Nodularity and subtle consolidation are seen within the right-upper lobe, with a raised horizontal fissure. 36b) Describe the chest CT findings (Fig. 36.2 ) The CT images reveal ill-defined scattered nodules, peripheral consoli- dation and areas of emphysema. 36c) Suggest a possible differential diagnosis for this presentation. The radiographic features are consistent with a chronic fibrotic reaction (volume loss and atelectasis), which may, in this case, be a result of the previous high-dose radiotherapy t reatment. Alternative causes of a chronic fibrotic reaction would include previous chronic empyema and old tuber- culosis. There is no evidence of fissural nodularity (e.g. sarcoidos is) or peripheral bilateral honeycombing (e.g. UIP). The clinical features (malaise, produc tive cough) are suggestive of a secondary infection and, given the presence of damaged area s of lung, a broad range of pathogens (including fungi) should be considered. 36d) What investigations would you arrange? Suitable investigations would include sputum culture (induced sputum, if necessary) with br onchoscopy and bronchoalveolar lavage (BAL), if unable to obtain sputum. Acid-fast bacilli stains and culture and fungal culture should be requested. CASE 36 307 Progress A single sputum culture was undertaken, which revealed moderate amounts of acid-fast bacill i on ZN staining. She was, therefore, commenced on quadruple therapy (rifampicin, isoniazid , pyrazinamide and ethambutol) while micro- biological sensitivities were awaited. She was reviewed 2 months after commencing therapy and was changed to a two-drug regimen (r ifampicin and isoniazid). One week later, final microbio- logical cultures from the sputum suggested mycobacteria avium complex (MAC). Questions 36e) What is the diagnosis at this stage? 36f) What is the next investigation? 36g) How would you manage this patient? CASE HISTORIES IN RESPIRATORY MEDICINE 308 Answers 36e) What is the diagnosis at this stage? Although the clinical features are consistent with a diagnosis of non- tuberculous mycobact erial (NTM) pulmonary infection, MAC has only been isolated in one microbiological sample ( sputum). This does not meet the criteria for diagnosis of NTM infection (see later), and fu rther investigations are required. 36f) What is the next investigation? Further microbiological samples are required to confirm the presence of an NTM to suggest a diagnosis of pulmonary infection (rather than air- way colonization). Bronchoscopy and bro nchoalveolar lavage should be considered if sputum is not diagnostic. Other diagnoses (e.g. Aspergillus , carcinoma, tuberculosis) should be excluded. 36g) How would you manage this patient? If MAC is the causative organism, the current antibiotic regimen is likely to be ineffectiv e. However, treatment of NTM requires prolonged ther- apy with potential side-effects, and therefore the priority in this case is to firmly establish diagnosis. Four further sputum c ultures (induced) were taken on two separate occasions, all of which consistently grew MAC. CASE 36 309 Questions 36h) Describe the main features of NTM pulmonary disease. 36i) Describe the diagnostic criteria for NTM pulmonary disease. 36j) How would you manage such a patient? CASE HISTORIES IN RESPIRATORY MEDICINE 310 Answers 36h) Describe the main features of NTM pulmonary disease. \227\206 Definition of NTM. NTM are ubiquitous environmental organisms, which do not belon g to the Mycobacterium tuberculosis complex or Mycobacterium leprae . Around 90% of disease due to NTM is pulmo- nary, with the remaining being superficial lymphadenitis (especially in children), skin or soft tissue infections, and disseminated disease in the immunocomprom ised. \227\206 Mycobacterium avium complex (MAC). This term includes either Mycobacterium avium or Mycobacterium intracellulare (two species that are difficult to differentiate), and are the commonest NTM to cause pulmonary disease, most often in patients with pre-existing lung disease (e.g. fibrosis, COPD, bronchiectasis). Clinical features may be non-specific (coug h, fatigue, weight loss, malaise). Disease is characterized by progressive pulmonary diseas e, usually in immuno- competent hosts. Three major clinical syndromes are described: Disease presenting similarly to Mycobacterium tuberculosis with systemic illness, upper lob e infiltrates and cavities, most often in elderly male smokers with COPD. Extensive parench ymal damage is not uncommon as presentation is often late, as the disease is usu- ally less aggressive than Mycobacterium tuberculosis . MAC in an area of pre-existing bronchiectasis (any cause but often prior TB or cystic fibrosis) Female non-smokers over 50 years old with no pre-existing lung condition, in association wi th interstitial shadowing (known as \200\230Lady Windermere syndrome \200\231). Associated systemic features may include bone marrow involvement (anemia, neutropaenia), ly mphadenopathy, hepatosplenomegaly, GI and liver involvement. Disseminated infection may occ ur in the immunocompromised. \227\206 Mycobacterium kansasii . Presents in a manner similar to M. tuberculosis , with c avitation in the majority of cases and bilateral disease in 20%. \227\206 Rapidly growing mycobacteria. These organisms grow in culture within 1 week and i nclude Mycobacterium fortuitum , Mycobacterium chelonae and Mycobacterium abscessus . This most often occurs as disseminated disease in the immunocompromised, particularly in HIV pos itive patients. CASE 36 311 36i) Describe the diagnostic criteria for NTM pulmonary disease. Diagnostic criteria (American Thoracic Society 2007). Requires all of the following: \227\206 Relevant symptoms \227\206 Consistent radiological abnormalities \227\206 Exclusion of other disease processes (e.g. fungal disease) \227\206 Microbiological confirmation of disease rather than colonization. Regardless of smear positivity, this requires at least one of: Two positive sputum cultures Single positive bronchoalveolar lavage Single biopsy (transbronchial or other) with consistent histology (granulomas) and positive culture Single biopsy with consistent histology plus positive sputum culture Positive culture from a privileged site (e.g. pleural effusion). Clinical features: \227\206 Often reflect the underlying disease (e.g. COPD, bronchiectasis) \227\206 Pulmonary symptoms (cough/dyspnoea/haemoptysis) \227\206 Systemic symptoms (malaise/fever/weight loss/lethargy). Radiology: \227\206 Variable according to type of NTM \227\206 HRCT is more sensitive in detecting many of the radiographic features of NTM disease \227\206 Think of NTM in cases of: Multiple small nodules Cavitatory disease Multifocal bronchiectasis Nodular infiltrates. \227\206 Cavitatory disease: 50% of MAC 90% of M. kansasii. \227\206 Nodules/bronchiectasis: 50% of MAC Most often seen in the right middle lobe. CASE HISTORIES IN RESPIRATORY MEDICINE 312 36j) How would you manage such a patient? Treatment principles: \227\206 Single agent therapy is not recommended \227\206 Sensitivities may be helpful in long treatment course, but in vitro may not reflect in vivo sensitivity \227\206 There are no randomized trials of therapy in immunocompetent hosts \227\206 Treatment is generally recommended until cultures have been repeatedly negative o ver a 1-year period and this usually involves at least 18 \200\22324 months treatment \227\206 It is recommended that drug toxicity (hepatic, GI, hematological, renal, vision) is monitored once monthly due to long duration of therapy \227\206 Newer evidence suggests that macrolides and quinolones may have a role (Jenkins et al . 2008) Regimens (daily): triple therapy in all cases. \227\206 Cavitatory MAC: Clarithromycin 500 \200\2231000mg OR azithromycin 250mg and Rifampicin 600mg or rifabutin 150 \200\223300mg and Ethambutol 15mg/kg. \227\206 Nodular MAC: Clarithromycin 1000mg OR azithromycin 500mg and Rifampicin 600mg or rifabutin 150 \200\223300mg and Ethambutol 25mg/kg. \227\206 M. kansasii : Isoniazid 300mg and Rifampicin 600mg and Ethambutol 15mg/kg. \227\206 Surgical options. Consider surgical resection in complicated cases where there is a combination of localized disease plus inability to toler- ate drug regimens, or presence of resistant strains (e.g. culture positive after 6 months treatment). Further reading Jenkins PA , Campbell IA , Banks J , Gelder CM , Prescott RJ , Smith AP ( 2008 ). Clarithro mycin vs ciprofloxacin as adjuncts to rifampicin and ethambutol in treating opportunist myc o- bacterial lung diseases and an assessment of Mycobacterium vaccae immunotherapy . Thorax ; 63 : 627 \200\223 634 . Zumla AI , Grange J ( 2002 ). Non-tuberculous mycobacterial pulmonary infections . Clin Chest Med ; 23 : 369 \200\223 376 . Case 37 A 45-year-old man with a 5-year history of COPD had become increasingly symptomatic in rece nt months, with frequent exacerbations and several admis- sions, receiving non-invasive ven tilation on one occasion. Dyspnoea during activities (such as getting dressed) and poor exe rcise tolerance limited him to walking around the house only (6-min walk distance markedly reduced at 140m). He was an ex-smoker with a 40 pack-year history, and had suffered with as thma since childhood. He had a right-sided pneumothorax a year previously, which failed to resolve with chest drain insertion and attempted talc pleurodesis. A Heimlich flutter valve was therefore substituted for the underwater seal in order to allow him to go home until t he pneumothorax resolved some months later. He suffered from low mood, which he attributed to ill health due to being unable to work an d difficulty looking after his children. He was on maximum inhaled therapy (steroids, a lon g acting beta agonist, and tiotropium), and required frequent courses of oral prednisolone and antibiotics. He had a squa- mous cell carcinoma removed from his cheek 6 months previou sly. Investigations Table 37.1 Pulmonary function tests Measured and (% predicted) values BMI(kg/m2) 30.2 FEV1(L) 0.6 (15%) FVC(L) 2.0 (43%) FEV1/FVC ratio 30% FRC(L) 6.4 (186%) RV(L) 4.9 (241%) TLC(L) 8.5 (121%) TLCO(mM/min/kPa) 5.48 (51%) KCO(mM/min/kPa/L) 0.8 (53%) CASE HISTORIES IN RESPIRATORY MEDICINE 314 Table 37.2 Arterial blood gasses pH 7.41 SaO2 (%) 89 PaCO2 (kPa) 7.3 PaO2 (kPa) 7.1 BE (mM/L) 9.2 \200\223 (mM/L) 31.6 HCO3 CASE 37 315 Question 37a) Discuss interventions, other than inhaled medications, that should be considered for this man. Give criteria for their use. CASE HISTORIES IN RESPIRATORY MEDICINE 316 Answer 37a) Discuss interventions, other than inhaled medications, that should be considered for this man. Give criteria for their use. Severe COPD is a common condition, with a large symptom burden for the patient, significant health-resource implications and a high mortality. Management aims to: \227\206 Reduce disease progression \227\206 Minimize exacerbation frequency \227\206 Ameliorate symptoms \227\206 Increase coping strategies. This man may be suitable for long-term oxygen therapy (LTOT) \200\224 oxygen supplementatio n for at least 15h a day. His single arterial blood gas fulfills the criteria for LTOT (PaO 2 <7.3 kPa, or <8.0 kPa in the pres- ence of hypercapnia or cor pulmonale), and he would n eed a further blood gas taken, when stable, to verify this. Oxygen is supplemented at a flo w rate sufficient to raise PaO 2 to >8kPa, without developing a rise in PaCO2 and thus resp iratory acidosis. It improves survival in selected patients with COPD and chronic hypoxia a fter at least 1 year of treatment, with those with greater degrees of hypoxia and cor pulmo nale receiving most benefit. He should be referred for pulmonary rehabilitation. This is of benefit for COPD patients wh o are dyspnoeic on walking but can manage at least 30m, and have an FEV 1 < 60% predicted. Pulmonary rehabilitation improves exercise tolerance and dyspnoea, is associated with reduc ed hospital stays and improvement in quality of life. A significant part of this course is exercise training, which patients are encouraged to continue long-term. Ideally all patients with COPD should be offered nutritional assessment and help in optimiz ing of weight. The patient in this case is overweight, which will increase his work of brea thing and oxygen requirements dur- ing exercise. This is better than being underweight, how ever, as this has an adverse impact on survival compared to those of normal or increased we ight. Optimizing nutrition is particularly important during exacerba- tions, especially if oral intake is impaired due to use of non-invasive or invasive ventilatory support, and fee ding via a nasogastric tube may need to be considered. This also applies to overweight pati ents, as a low albu- min, phosphate or magnesium may have an adverse impact on recovery and weaning from ventilation. CASE 37 317 This man could have a trial of low-dose opiates or benzodiazepines before activities that h e knows make him breathless, such as getting dressed, with the aim of relieving dyspnoea an d anxiety. Titrated in small doses they do not lead to worsening hypercapnia or premature d eath. Non-invasive ventilation is of benefit during acute hypercapnic, acidotic exacerbations; ho wever, there remains insufficient evidence to recom- mend long-term home use in COPD, even in the presence of a chronically raised PaCO 2 . Occasionally, in carefully selected cases, surgical treatment, such as lung volume reductio n surgery, bullectomy or transplant can be considered, and these are discussed further belo w. Given the poor prognosis of severe COPD, patients and their carers should be given the oppo rtunity to discuss end-of-life wishes, including ITU admissions in the future. Fig. 37.1 CXR. Questions 37b) Describe the features illustrated by the CXR ( Fig. 37.1 ). 37c) What further imaging is required to decide whether a patient may benefit from lung transplantation? CASE HISTORIES IN RESPIRATORY MEDICINE 318 Answers 37b) Describe the features illustrated by the CXR ( Fig. 37.1 ). The CXR shows hyperinflated lung fields. A large area of lucency is seen at the right apex, which is almost certainly related to a bulla, rather than a pneumothorax (supported by the concave inferior margin). Callus formation due to old rib fractures are seen at the left b ase. 37c) What further imaging is required to decide whether a patient may benefit from lung transplantation? Further imaging required when considering lung transplantation. A CT-chest is required to e xamine the distribution of lung disease, and to exclude other factors that might contra-ind icate transplant, such as a lung cancer. An echocardiogram and bone densitometry are also r equired, as a poor ejection fraction, or osteoporosis would make trans- plant surgery too h igh risk. (a) (b) Fig. 37.2 CT chest. (a) upper zone and (b) mid zone. CASE 37 319 Questions 37d) Describe the features illustrated by the CT-chest ( Fig. 37.2a and b). 37e) Discuss the factors in this man \200\231s case that should be taken into account when deciding whether or not he should be considered for lung transplantation. 37f) How may survival in COPD be predicted? CASE HISTORIES IN RESPIRATORY MEDICINE 320 Answers 37d) Describe the features illustrated by the CT-chest ( Fig. 37.2a and b). The upper zone CT chest slice (Fig. 37.2a) confirms right apical emphy- sematous changes wi th bullae formation. The mid zone CT chest slice (Fig. 37.2b) shows moderate centrilobar em physema in both lung, and, although multiple slices are not shown, this was seen throughout the rest of the lung fields. 37e) Discuss the factors in this man \200\231s case that should be taken into account when deciding whether or not he should be considered for lung transplantation. Factors to take into account when considering transplant referral. Surgical intervention is only appropriate for a small minority of patients with severe COPD due to the strict eligi bility criteria and limited organ supply; however, it should still be considered. Lung tran splantation in COPD may improve exercise tolerance and quality of life for carefully select ed patients. However, deciding the optimal time of referral is challenging; many patients s uffer for years with significant symptoms, making it difficult to identify patients with a high short-term mortality risk. The survival advantage of lung transplant in COPD (82% at 1 year, 49% at 5 years) compared to survival without transplant is not fully known. Selectin g patients at the more severe end of the spectrum increases the probability that transplant will improve survival, so long as comorbidity does not increase operative risk unreasonabl y. The man in this case has a significant predicted mortality based on several criteria des cribed in answer (37f), and therefore transplant should be considered. Contraindications to transplant. This man has no absolute contraindi- cations: he is not a current smoker, and, although an active malignancy within the previous 2 years is a contrai ndication, basal and squamous cell carcinoma of the skin are exceptions to this. Medical co nditions, such as diabetes and hypertension, are relative contraindications only if they ar e not well controlled or have resulted in end-organ damage. Oral prednisolone is no longer a contraindication to transplant unless there is associated osteoporosis, though attempts s hould be made to minimize the dose, to less than 20mg/day at least. This man would need eva luation of his mental health and adherence to previous therapies, as poorly controlled psyc hoaffective disorders, often leading to poor adherence to therapy, are relative contraindic ations to transplant. Cyclomegalovirus CASE 37 321 is no longer a contraindication to transplantation, as infection can be prevented or contro lled with ganciclovir. One of the considerations for this man is his previous talc slurry pleu- rodesis. This woul d make any form of thoracic surgery longer and more difficult, although does not affect the eventual outcome; there is a higher risk of bleeding and greater inotropic requirement and , in lung volume reduction surgery, the risk of a prolonged air leak is increased. It is th ought that prior abrasion pleurodesis may result in fewer surgical complications than talc slurry pleurodesis. In terms of other pleural pro- cedures, a previous full pleurectomy wou ld be an absolute contraindica- tion to transplant. 37f) How may survival in COPD be predicted? Predicting survival in severe COPD. Data from the National Emphysema Treatment Trial (NETT) , suggested that patients with COPD and an FEV1 <20% predicted, as does the man in this cas e, and have a median survival of 3 years. This study also found a TLCO <20%, or homogenous disease on high-resolution computed tomography, to be predictive of poor prognosis. The \200\230BODE \200\231 index takes more factors into account, and was specifically deve loped to help predict survival in COPD. It is based upon B ody mass index, the degree of ai rflow O bstruction (% predicted FEV 1 ), D yspnoea (modified Medical Research Council dyspn oea scale) and E xercise toler- ance (6-min walk distance). The man in this case has a BODE index of 8, which would suggest a median survival of 3 years. He has also had a hos- pital admission with an exacerbation complicated by hypercapnia (PaCO 2 >6.0kPa); such patients have a median 2-year survival of only 50%. Additional poor prognostic factors are pulmonary hypertension, hypoxaemia, hypercapnia mult iple exacerbations, and a low haematocrit. Question 37g) What factors would need to be taken into account, if considering referral for lung vol ume reduction surgery (LVRS), compared to transplant? CASE HISTORIES IN RESPIRATORY MEDICINE 322 Answer 37g) What factors would need to be taken into account, if considering referral for lung vol ume reduction surgery (LVRS), compared to transplant? The rationale of LVRS is to improve the mismatch between the size of the lungs and of the t horacic cavity by removing space-occupying, hyper- inflated, emphysematous areas of lung th at contribute least to gas exchange. In the remaining lung, the hope is to improve elastic recoil and airways resistance by allowing it to expand. It is, therefore, of greatest benef it in patients with heterogenous disease. This is borne out by the Nation Emphysema Treatme nt Trial (NETT), in which LVRS led to an improvement in exercise capacity and quality of li fe in \200\230all comers \200\231, but only reduced mortality in patients with predominant upper-lobe disease. The man in this case could, theoretically, be considered for LVRS as he has heterogenous di sease, with marked bullous emphysema in his right- upper lobe. He could also, theoretically , be considered for bullectomy, as he has an isolated bulla occupying >30% of a hemithorax, with relatively underexpanded underlying lung. However, he has an FEV 1 <20% pre- dicted, putting him at high mortality risk from surgery. Other factors (not relevant to this patien t) making LVRS or bullectomy a higher risk than medical therapy alone, are TL CO <20% predi cted, homogeneous disease on CT scan, PaO 2 <6kPa, bronchiectasis with chronic sputum produ ction, age >70 years old, pulmonary hypertension (peak systolic pulmonary arterial pressure of >50mmHg) and previous thoracic surgery. Advantages of LVRS or bullectomy over transplan t are that they are not constrained by a limited organ supply and, of particular relevance to the patient in this case, life-long immunosuppression is not required; the necessity of 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.