The prevalence of individual histological patterns differs Bronchiectasis. This may occur in many forms of CTD at least in part related factors descri bed above. It is par- ticularly a problem in RA and Sjogren \200\231s disease. Treat- ment is described in Chapter 10.2 with the additional recognition of potential relative immunoco mpromise. \200 Pleural effusion. This is most commonly associated with rheumatoid disease . It may resolve with systemic treat- ment but may be an isolated presentation. Speci \201 c treat- ment is discussed in Chapter 14.8. strikingly between CTD and non-CTD related IIP. AUTHOR \200\231S TIP The range of HRCT appearances from ground glass to reticular does not translate into corresponding differ- ences in outcome in SSc and is unproven in other CTDs. \200 In the only large study of lung histology in SSc, there was a high prevalence of NS IP (62/80, 75%) and a very low prevalence of UIP (6/80, 8%).The HRCT features of lung disea se in SSc can range from predominant ground-glass attenuation to a predominant reticular pa ttern and are broadly similar to the range seen in idiopathic NSIP. Coarse reticulation and honeycombing are more unusual. \200 Overall outcome differs little between UIP and NSIP in SSc, even after adjustment for baseline disease severity \200 UIP in SSc has a better outcome than IPF, perhaps re \202 ect- ing a lower profusion of \201 broblastic foci in UIP in CTD in general or earlier diagnosis of the lung disease. CTD: speci \201 c diagnosis CTDs differ in the frequency with which speci \201 c lung com plications occur. Certain common principles apply in terms of investigation and diagnosis, especially where ILD is concerned. \200 Many of the principles described in other chapter s for the general management of the ILD also apply to con- nective tissue disease associate d ILD in particular relat- ing to lymphocytic interstitial pneumonia (Chapter 7.6) and obli terative bronchiolitis (Chapter 7.7) NSIP is the predominant histological diagnosis in CTDs, Rheumatoid arthritis is the commonest of the CTDs to be associated with ILD, but data on tr eatment are limited. \200 Systemic sclerosis (SSc) is much less prevalent than rheumatoid arthritis but is more commonly complicated by ILD and the evidence base is much more exten sive. \200 Not all the recent advances in understanding of the natural history of the IIP s can be extrapolated to their CTD-associated counterparts. with the possible exception of RA, HRCT re \202 ects this to some extent but there tend to be particular HRCT pro \201 les a ssociated with speci \201 c CTD. \200 Other than for SSc, data on treatment outcomes in rela- tion to HRCT pattern have yet to emerge in suitably large series. CHAPTER 7.10 Pulmonary manifestations of connective tissue disorders 157 Management principles No formal placebo-controlled trial has been performed in lung disease in CTD current management is based on anecdotal and inconclusive retrospective data. The d eci- sion to treat must be largely based on the likelihood, in individual patients, that th e risk of therapy (drug toxicity) will be outweighed by the bene \201 t (protection agains t pro- gression of disease). Apart from a minority of patients with predominantly HRCT in \202 ammatory appearances, therapy is aimed at slowing or preventing progression, rather th an in the hope of a striking short term response. Early lung involvement in PM/DM is an imp ortant exception to this rule (see below) Treatment issues, including the question of which patients to treat and the selection of therapeutic agent, have been most widely explored i n SSc, perhaps because IIP is most prevalent in that disease. In SSc, the threshold for int roduc- ing treatment is reduced when: \200 The duration of systemic disease is short (<4 years), indicating a higher risk of progression of lung disease \200 Disease is severe, a s judged by pulmonary function tests and the extent of \201 brosis on HRCT. TLCO provides a stronger prediction of mortality and correlates better with the extent of disease on HRC T than other lung function variables. Other immunosuppressive agents such as azothiaprine have been used but data are limited. Treatment in RA \200 There is an extreme paucity of data for the management of IIP in RA. IIP in RA may result from the disease itself or as a consequence of its treatment e.g. meth otrexate (MTX)- induced pneumonitis, the two sometimes being indistin- guishable. A smoking history of >25 pack years increases risk. Current treatment recommendations are based on anecdote. Oral prednisolone 0.5mg/kg/day for 1 \200\2233 months, weaned to 10mg/day or 20mg/alternate days if there is improvement. Immunosuppressant treatment such as cyclophospha- mide, azathioprine, D-penicillamine, MTX and cyclospo- rin-A have been used in cases of treatment failure or progression. Anti-tumor necrosis factor (TNF)-alpha therapy has been reported to induce both both bene \201 t and exacer- bation of RA-associated IIP. Cyclophosphamide can also be useful for the treatment of MTX-induced pneumonitis, which has not responded to the usual management of MTX withdrawal, oxygen therapy and/or corticoster oids. There is evidence of recent deterioration, as judged by symptomatic worsening and/or, a dec line in serial pul- monary function tests. Ongoing deterioration in treated patients is mor e predictive of mortality than any clinical feature at presentation. Cryptogenic organizing pneumonia (COP) in RA is highly likely to respond to corticosteroids. Treatment in PM/DM \200 Acute fulminant disease may require high-dose IV meth- HRCT appearances are strongly suggestive of predomi- nantly in \202 ammatory disease (seen in a minority of cases) \200 BAL remains contentious, with opposing views that a BAL neu trophilia identi \201 es greater risk of progression or merely greater disease severity at the time of sampling. \200 In the absence of a strong evidence base, these broad ylprednisolone (1.0g daily for 3 days) Less severe disease oral prednisolone 0.75 \200\2231.0mg/kg per day (or equivalent) followed by gradual weaning. In patients with a suboptimal response or adverse effects from corticosteroids, considerati on should be given to second-line therapies with either immunosup- pressant or cytotoxic ag ents as described for RA. considerations may be applied to other CTD. Treatment in SSC \200 Outcome in the IIP of SSc is substantially better than outcome in I PF, after adjustment for baseline disease severity. Complete remission as judged by serial HRCT is rare. Even with aggressive therapy, severe interstitial \201 brosis remains a maj or poor prognostic feature. Prognosis is good with early treatment. Short-term improvement is seen in greater than 90%. Patients with elevated CK levels have a 3-fold better response. In the longer term, respon se rates are resolution occurs in >70% and is re \202 ected in long term survival. High dose corticosteroid should not be used as it is CTD- associated pulmonary hypertension Pulmonary hypertension had been most intensively stu d- ied in SSc where its relationship to the underlying CTD as a lone pulmonary vasculopathy has been recognized. This has led to clear cut investigation (including annual echocardiog raphy) and treatment pathways as described in Chapter 12.2. The advances in understanding o f PHT in SSc cannot necessarily be extrapolated to other CTDs. The presence of pulmonary hy pertension in other CTDs, often in the presence of other pulmonary pathology, e.g. COPD, II P is not well characterized. Conventional treatment of asso- ciated lung pathology and corr ection of hypoxaemia must be undertaken as initial steps and may correct \200\230simple \200\231 hypoxaemic pulmonary vasoconstriction. Further investi- gation and management can be considered as described in Chapter 12.2. associated with renal crises. Current treatment recommendations (initial low dose corticosteroid therapy (e.g prednisolon e 10mg daily) and an immunosuppressive agent, usually oral cyclo- phosphamide (1.0 \200\223 1.5mg/kg)) are based on open observational data and retrospective comparisons of serial cli nical data between treated and untreated. In a recent large multicentre study in SSc-associ ated IIP ( relatively mild disease) the difference in lung func- tion, whilst statistically signi \201 cant was modest and given the potential long term toxicity, does not justify t he rou- tine use of oral cyclosphamide in unselected patients with SSc. Pulsed intravenous cyclophosphamide (500 \200\2231000mg at dose intervals of 2 \200\2234 we eks) has been evaluated and open therapy was associated with evidence of partial regression of IIP, based upon serial PFT or HRCT and treatment was well-tolerated. Placebo-controlled trials comparing oral with IV cyclophosphamide are awaited. A MILLAR 158 CTD-associated muscle weakness Muscle weakness of the respiratory muscles and diaphragm alo ne can lead to breathlessness without any intrinsic lung involvement and are most common in PM/DM. A number of the CTDs can lead to isolated uni or bilateral diaphragm palsy whether directly or due to phrenic nerve palsy (Fig. 7.10.1) SLE is the characteristic condition in which \200\230shrinking lung \200\231 occurs and co ntroversy continues as to whether this is due to a combination of muscle weakness and resul tant under- lying lung disease or intrinsic lung pathology/microembolic phenomenon. Treatme nt is of the underlying CTD and recovery can occur. Diaphramatic pacing has been relatively unsuccessful. Further reading Pulmonary Manifestations of Systemic disease 2005; 10: Monograph 34. Thorax 2008, DPLD guidelines in press. Fig. 7.10.1 Unilateral diaphragm palsy in a patients with SLE. This page intentionally left blank R WINTER 160 7.11 Pulmonary manifestations of systemic diseases Overview Many systemic diseases can pres ent with symptoms and signs of lung involvement. Pulmonary manifestations may also develop during the course of a large number of long term conditions. However, lung disease is commo n and its association with systemic disease may be casual rather than causal. Occasionally, lung disease may arise as a com- plication of treatment. This chapter will give an account of pulmonary manifesta- tions of systemic diseases not considered elsewhere in this handbo ok \200\223 gastroenterological, liver, endocrine, renal, hematological, cardiac and neuro logical diseases. Investigation Chest radiography Gastroenterological diseases Upper airway and esophagus Pharyngeal pouch and abnormalities of the upper airway Post-deglutition aspiration occurs in the majority of larger pouches bu t is uncommon in small pouches. Video- \202 uoroscopy allows assessment of signi \201 ca nt aspiration \200\223 an overlooked cause of recurrent pneumonia for which surgery is occ asionally needed (Fig. 7.11.1). Tracheo-oesophageal \201 s- tula is a rare but important cause of recurrent aspiration pneumonia. Fig. 7.11.2 Chest radiograph in a critical care patient performed following an acute respir atory deterioration shows extensive bilateral consolidation. This is most marked in the per ihilar regions and lower zones corresponding to the most dependent portions of the lungs (a pical and posterior segments of the lower lobes) Investigation Contrast swallow radiography Pancreatitis Acute pancreatitis is associated with acute lung injury, pneumonitis and hypox aemia that may develop into ARDS. Patients with pancreatitis may have pleural effusion whic h is more commonly left sided. A grossly raised pleural \202 uid amylase is diagnostic. P leural effusion is associated with poor prognosis. In \202 ammatory bowel disease One-third of patients with in \202 ammatory bowel disease have signi \201 cant extra-colonic manifestations. Pulmonary manifestations are being incr easingly recognized as an important accompaniment of in \202 ammatory bowel disease with a s many as two thirds of patients having at least one respiratory symptom. Minor abnormaliti es in lung function are common and bronchial hyper-responsiveness occurs in 40% patients. L ung disease is usually related to disease activity and may affect any part of the lungs. It may develop years after the onset of bowel disease. Fig. 7.11.1 A frontal projection from a contrast swallow examination shows a large contrast medium \201 lled pharyngeal pouch in its characteristic location. There is no aspiration of contrast medium into the trachea Tracheo-bronchitis and airway hyperresponsiveness Changes in in \202 ammatory and pro-in \202 ammatory mediators in the airway, coupled with alteration in vascular permea- bility h ave con \201 rmed that the lung is a target organ in inflammatory bowel disease. Cough and wheeze and occasionally large airway ulceration/mass can be present- ing symptoms of Crohn \200\231s disease and ulcerative colitis. Gastro-oesophageal re \202 ux (GORD) GORD is common, affecting up to one third of people, in the presence and absence of hiatus hernia. The role of GORD in cough and asthma is revie wed in the relevant sections (see Chapters 4 and 5). GORD and recurrent aspiration is seen in oesophageal dysmotility in sclero- derma or in neurological disorders such as motor neur on disease (MND) and multiple sclerosis. Ambulatory oesoph- ageal pH monitoring and endosco py have a relatively poor sensitivity and a therapeutic trial of proton-pump inhibi- tors i s considered to be a reasonable initial diagnostic step. Aspiration is a signi \201 cant r isk factor for pneumonia in the intensive care environment (Fig 7.11.2). Bronchiectatasis The observation of bronchiectasis developing a short interval after colect omy for in \202 ammatory bowel disease has led to further research and understanding of th is important association (Fig. 7.11.3; see Chapter 11). Investigations Lung function \200 Airways obstruction (including small airways obstructio n). \200 Air-trapping. \200 Reduction in transfer factor. CHAPTER 7.11 Pulmonary manifestations of systemic diseases 161 CT radiography \200 Air-trapping. \200 \200\230Ground glass \200\231 appearance, indic ating alveolitis. \200 Obliterative bronchiolitis. \200 Bronchiectasis. may involve the local overproduction of nitric oxide. Hepatopulmonary syndrome is associate d with substan- tially increased mortality. Symptoms and signs \200 Finger clubbing/signs of severe liver disease. \200 Cyanosis ca n re \202 ect severe hypoxaemia. \200 Normal breath sounds. Investigation Lung function \200 Reduced SpO2. \200 Reduced gas transfer (with normal s pirometry and lung volumes). Demonstrable right-to-left shunt. Chest radiography A diffusely abnormal chest radiograph i s seen in approxi- mately 50% cases. Porto-pulmonary shunting In severe portal hypertension anastomoses may develop between the portal and pulmonary circulation. Fig. 7.11.3 Expiratory image of HRCT in a patient with ulcerative colitis shows widespread bronchiectasis with air trapping in keeping with small airways obstruction. Pulmonary hypertension Rarely, severe pulmonary hypertension complicates cir- rhosis of the liver. AUTHOR \200\231S TIP Early recognition of lung involvement in bronchiectasis is important a s the disease is often strikingly steroid- responsive in early stages. Pleural effusion Pleural effusion is a common consequence of hypoalbu- meniaemia. Communica tions between the peritoneal and pleural cavities may account for pleural effusions seen pa tients with ascites. Treatment and complications Aminosalicylates Aminosalicylates such as sulphasalazine may be associated with a pneumonitis that can progress to pulmonary \201 bro- sis. Peripheral b lood eosinophilia is seen in 50% cases. The chest radiogarph may show pulmonary in \201 lt rates. Fulminant hepatic failure and ARDS Fulminant hepatic failure is associated with failure of all functions of the liver with impairment of synthetic function leading to hypoalbuminaemi a, coagulopathy and the hepa- torenal syndrome. Fulminant hepatic failure causes changes to the permeability of the alveolar-capillary network leading to increased lung water, pulmon ary oedema and ARDS. Anti -TNF 2 alpha treatment Humanized monoclonal antibodies against tumor necrosis factor ( TNF) 2 alpha are effective in the treatment of Crohn \200\231s disease. Anti-TNF 2 alpha tr eatment is associated with a 4-fold increased risk of reactivation of tuberculosis, the maj ority of cases presenting within 12 weeks of starting therapy. Patients should be assessed for risk and for the presence of latent tuberculosis before starting treatment, in accordan ce with British Thoracic Society guidelines. AUTHOR \200\231S TIPS \200 Hypoxaemia is common in liver disease \200\223 full lung func tion testing should be performed in all patients with signi \201 cant liver disease. An un explained isolated reduction in transfer factor is likely to re \202 ect pulmo- nary micro -arteriovenous shunting. Consider occult respiratory infection as a precipitat- ing factor in fulminant hepatic fail ure \200\223 CT scan of the lung may be highly informative. Liver diseases Overview Patients with liver disease are more susceptible to respira- tory infection, particularly p neumococcus. Unexplained refractory hypoxaemia and impaired lung function is commonly seen in advanced liver disease. Char- acteristically, lung function will show a substantially re duced transfer factor for carbon monoxide. Signi \201 cant impair- ment of lung function i s often asymptomatic but can pres- ent management dif \201 culties when patients are consi dered for transplantation. Pulmonary arterio-venous malformations \200\223 the hepatopulmo nary syndrome Endocrine diseases Obesity Breathlessness is a common symptom in obesity and insu- lin resi stance. This is due to several factors \200\223 reduced lung function, reduced aerobic cap acity and impaired respira- tory muscle and diaphragmatic function. Waist circumference may be a better predictor of reduction in lung function than body mass index. Investigation Lung function Mild obesity: \200 Reduced FEV1. \200 Reduced VC. \200 Re duced static lung volumes. Multiple microscopic (and occasionally macroscopic) shunts occur between the small pre-capi llary pulmonary arteries and veins in about 20% patients. The explanation for this vascular remodeling is not fully understood but R WINTER 162 Severe obesity: \200 Reduced FEV1. \200 Reduced VC. \200 Reduced transfer factor. \200 Obstructive sleep apnoea. \200 Type 2 respiratory failure. Weight reduction is asso ciated with a reduction in self assessed breathlessness and improved 6MWT. Diabetes mellitus Diabetes mellitus is associated with minor abnormalities of ventilatory c ontrol and lung function. Diabetic alveolar microangiopathy and respiratory autonomic neuro pathy are both well recognized. With the exception of gross hyperven- tilation (Kussmaul \200\231s respiration) \200\223 a feature of diabetic keto- acidosis \200\223 pulmonary i nvolvement in diabetes is almost always sub-clinical and is rarely the presenting complaint . Better understanding of the natural history and patho- physiology of diabetic alveolar mi croangiopathy is of rele- vance to the emerging use of inhaled insulin. Fig. 7.11.5 Saggital CT reconstruction con \201 rms the anterior mediastinal location and contiguity with the thyroid gland in the neck. The appearance is typical of a large thyroid goiter. Thyroid disease Breathlessness, a common symptom in hyperthyroidism, may result from increa sed central respiratory drive. Respi- ratory muscle weakness is due to the metabolic effect of hyperthyroidism on the diaphragm and other respiratory muscles. These features all reve rse with treatment. Large thyroid goiter can cause progressive breathlessness (and occasion ally stridor) due to tracheal displacement and compression. Tracheal compression is usually extra- thoracic but may also extend into the thorax. Thyroid goiter may be a major factor in obstructive sleep apnoea with occasionally dramatic response to thyroidectomy. AUTHOR \200\231S TIP Consider thyroid disease and goiter in patients with unexplained breat hlessness or obstructive sleep aponea. Acromegaly Patients with acromegaly have a 3-fold increased mortality and respiratory condi tions are thought to account for around 25% of this increased risk. Symptoms and signs \200 Thyroid goiter ? extending retrosternally. \200 Tracheal displa cement. \200 Stridor. Symptoms and signs \200 Nasal polyps. \200 Voice changes. \200 Obstructive sleep apno ea syndrome (>50% patients Investigation Lung function \200 Air \202 ow obstruction. \200 Proportionately a large r reduction in PEF than FEV1. \200 Characteristic \202 ow-volume loop. \200 Abnormal sleep study. Chest radiography with acromegaly). Pneumomegaly \200\223 an increase in the number of alveoli. Renal diseases Peritoneal dialysis The incidence of hydrothorax, or pleural leak, in perito neal dialysis is unclear. Acute hydrothorax leading to a massive pleural effusion is rare \200\223 a high sugar level in the effusion can be used to con \201 rm that the pleural \202 uid is dialysate. Peritoneal dialysis affects intravascular volumes and will alter lun g mechanics. All patients undergoing dialysis may experience changes in lung water, that ma y occasionally present as \202 ash pulmonary oedema \200\223 the accumulation of \202 uid into the pulmonary interstitium over a matter of minutes or hours. Investigation Lung function \200 Reduced FEV1 and FVC. \200 Reduced transfer factor, th at may persist after renal transplant. Renal artery stenosis May present as \202 ash pulmonary oedema. Chronic anemia Breathlessness in chronic renal failure is common and partly accounted for b y chronic anemia, which reduces Fig. 7.11.4 Chest radiograph demonstrates a large superior mediastinal mass extending to bo th sides of the midline and deviating the trachea but not compromising its lumen. CHAPTER 7.11 Pulmonary manifestations of systemic diseases 163 the oxygen carrying capacity of blood and will limit tissue oxygen delivery. Erythropoietin improves self-assessed breathlessness and exercise capacity. Bone marrow transplantation Early non-infectious complications typically include: \200 Pu lmonary oedema. \200 Upper airway complications. \200 Diffuse alveolar hemorrhage. \200 Pleural effusion. Late non-infectious complications: \200 Bronchiolitis obliterans. \200 Graft versus host disease. \200 Radiation induced lung injury. Drugs The lung has a susceptibility to injury with a large number of chemotherapeutic agents. Bleomycin and b usulphan are amongst the more common. Bleomycin causes severe lung disease early after trea tment - 10% patients who have received 500mg of bleomycin or more will develop fatal pulmon ary \201 brosis. Pulmonary toxicity is rare below a cummulative dose of 150mg. Busulphan, the \201 rst cytotoxic drug to be linked with pul- monary toxicity, causes hyperplasia o f the type 2 pneumo- cyte. Chronic exposure, particularly when combined with other cytotoxi c drugs, is associated with the development of pulmonary \201 brosis. Hematological disorders Lymphoma The lung parenchyma may be involved in approximately 10% p atients with lymphoma at presentation and approxi- mately 30% have lung involvement at some stage. Hodgkin \200\231s disease can occasionally present with discrete masses in the lung in the absence of generalized lymphadenopathy. The major differential diagnosis is often o pportunistic infection, diffuse alveolar hemorrhage or drug reaction. Pleural effu- sions o ccur in approximately 30% patients with lymphoma and, again, the major differential diagnos is is infection. Hilar and mediastinal lymphadenopathy is common. Occasionally, giant media stinal lymph nodes compress or invade larger airways with progressive breathlessness and th e development of stridor. Emergency airway manage- ment with careful intubation may be requ ired. The use of the very low density gas helium mixed with oxygen \200\223 given alone or in association with non-invasive ventilation \200\223 can be life-saving, by reducing the work of breathing. Mediasti- nal lymphadenopathy can compress the great veins, pro- ducing superior vena cava syndrome. Investigation CT radiography Cardiac diseases Lung water is increased if left atrial pressure is greater than plasma onc otic pressure. Increased lung water manifests as acute or chronic pulmonary oedema, peri-br onchial \202 uid or as transudative pleural effusion, which may be unilateral. Acute elev ation in left atrial pressure can also be associated with pulmonary hemorrhage and signi \201 cant haemoptysis. Chronic elevation of left atrial pressure, as seen in mitral valve d isease or refractory left ventricular failure, produces a chronic elevation of pulmonary ve nous pressure and remodeling of the pulmonary vasculature. This is best seen in mitral sten osis where lung function abnormalities are: \200 Reduced FEV1. \200 Reduced VC. \200 Reduced transfer factor. \200 Bronchial hyperresponsiveness. Amiodarone Amiodarone, used in the treatment of both supraventricu- lar and ventricular arythmias is recognized cause o f drug- induced lung disease, Amiodarone-induced lung toxicity is usually seen in patients who have received larger doses (>200mg/day) over prolonged periods. Approximately 6% of pat ients taking more than 400mg amiodarone for 2 months or more will develop pulmonary toxicty . The mechanism is both immunologically mediated and through a direct toxic effect. Symptom s are of cough, breathless- ness and occasionally pleritic pain. The major differential dia gnosis is worsening cardiac failure or infection. Advanced age and pre-existing lung diseas e are risk factors. The disease is reversible if treatment is stopped early but the long ha lf life of amiodarone (28 days) confers slow resolution. CT appearances commonly seen inclu de high attenuation pleural and parenchymal lesions, pleural thick- enting and non-speci \201 c in \201 ltrates. High attenuation of the liver re \202 ects the iodine content of the drug (Fig. 7.11.7). Fig. 7.11.6 CT image at the level of the carina shows extensive medistinal lymphadenopathy with encasement of the ascending aorta and superior vena cava with narrowing of both main b ronchi. Leukemia Leukaemic pulmonary in \201 ltrates may occur which may be alveolar, interstitial , peribronchial or perivascular. Occult pulmonary hemorrhage can also occur. Opportunistic infection is the major important differential diagnosis, with aspergillus and cytomegalovir us amongst the most com- mon infective agents. Pneumocystis carinii is uncommon if the pati ent has received correct prophylaxis. Lung biopsy may be valuable in distinguishing non spe ci \201 c lung injury due to pulmonary toxic chemotherapy, infec- tion, obliterative bronc hiolitis or leukaemic in \201 ltrates. R WINTER 164 Investigation CT radiography decline of lung function. It may be offered to patients whose VC has fallen to below 50% of predicted value. Each individual patient will need to be involved in this decision along w ith the palliative care team. Ventilatory support is not suitable for all patients with MND but experience has shown that in 30% it is associated with improvement in quality of life. AUTHOR \200\231S TIPS \200 Measurement of VC provides the best generally avail- able beds ide test for serial assessment of the respiratory muscle pump. Peak expiratory \202 ow rate (PEFR) \200\223 a test that measures \202 ow for 0.01 sec onds is a poor test of the respiratory muscle pump. Further reading Arguedas MR, Abrams GA, Krowka MJ, et al. Prospective evaluation of outcome s and predictors of mortality in patients with hepat- opulmonary syndrome undergoing liver transplantation. Hepatology 2003; 37(1): 192 \200\223197. Fig. 7.11.7 HRCT image at the level of the inferior pulmonary veins in a patient with progr essive breathlessness, one month following commencement of amiodarone therapy. There is ext ensive bilateral ground glass opacity and \201 ne reticulation. This resolved following c essation of amiodarone and corticosteroid therapy. Dakin J, Kourteli E, Winter R. Making Sense of Lung Function. Arnold 2003. Gaines DI, Fallon MB. Hepatopulmonary syndrome.Liver Int 2004; 24(5): 397 \200\223401. Gastro-oesophageal re \202 ux treatment for prolonged non-speci \201 c cough in children and adults.Cochrane Database Syst Rev 2006; 18(4): CD004823 Neurological diseases Neurological disease can manifest as bulbar and laryngo- pharyngeal p roblems leading to aspiration pneumonia. Neurological disease also commonly affects the res pira- tory muscle pump \200\223 leading to hypoventilation and the development of type 2 r espiratory failure. Joint Tuberculosis Committee of the British Thoracic Society. Recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-A treatment. Thorax 2005; 60: 800 \200\223805. Kadhim AL, Sheahan P, Timon C. Management of life-threatening airway obstruction caused by benign thyroid disease. J Laryngol Otol 2006; 120(12): 1038 \200\2231041. Epub 2006 Sep 25. Stroke Following signi \201 cant stroke the majority of patients will aspirate with foodst uffs when this is assessed by video \202 uo- roscopy and in almost one half this may be si lent aspiration (i.e. without choking). Tests of swallowing supplemented by video \202 uor oscopy are essential. Swallowing musculature is bilaterally represented in both motor corti ces and many patients regain a safe swallow over a relatively short period. Dysphagia, howe ver, confers a 7-fold increased risk of aspiration pneumonia and is an important predictor of increased mortality. Mackle T, Meaney J, Timon C. Tracheoesophageal compression associated with substernal goite r. Correlation of symptoms with cross-sectional imaging \201 ndings. J Laryngol Otol 2007 ; 121(4): 358 \200\22361. Mahadeva R, Walsh G, Flower CD, et al. Clinical and radiological characteristics of lung di sease in in \202 ammatory bowel disease. Eur Respir J 2000; 15(1): 41 \200\22348. Poelmans J, Tack J. Extraoesophageal manifestations of gastro- oesophageal re \202 ux. Gut 2005; 54(10): 1492 \200\2231499. Raghu MG, Wig JD, Kochhar R, et al. Lung complications in acute pancreatitis. JOP 2007; 8(2): 177 \200\223185. MND MND frequently is associated with death within 5 years of diagnosis. The use of positiv e pressure non-invasive ventila- tion has been shown to improve survival and rate of 165 Chapter 8 Infection Chapter contents 8.1 Community-acquired pneumonia 166 8.2 Hospital-acquired pneumonia 172 8.3 Aspiration syn dromes 176 8.4 Lung abscess 180 8.5 Nocardia and actinomycosis 182 8.6 Viral infections of the respiratory tract 184 8.7 Respiratory tuberculosis 188 8.8 Non-respiratory tuberculosis 192 8.9 Opportunist (non-tuberculous) mycobacteria 194 8.10 Fungal and parasitic lung dise ase 196 W-S LIM 166 8.1 Community-acquired pneumonia: diagnosis and clinical features \200 \200 Epidemiology Data from population studies have reported an incidence of CAP diagnosed in th e community of 5 \200\22311 per 1000 adult population. The incidence of CAP requiring hospi tal admission has been reported at 1 \200\2234 per 1000 population. Of those admitted to ho spital in the UK, around 5% are managed in a critical care setting. Mortality rates for pat ients treated in the community are very low (<1%) while average mortality rates for hospita lized patients range from 6 \200\22314%, rising to >30% in patients with severe CAP. Incide nce and mortality rates are highest in the elderly. Pulmonary hemorrhage. Pulmonary embolism. Pulmonary oedema. Pneumonia admissions and deaths (n=1339) 400 Survived Died 350 300 s t n e i t a p 250 f 200 o r e b m u N 150 Fig. 8.1.2 Bronchoalveolar cell carcinoma presenting as extensive consolidation on CXR. 100 50 Clinical features In the elderly, mental confusion and the lack of fever at presentation ar e more common than in younger patients. Pleuritic chest pain is more common in younger pati ents and has been associated with a good prognosis. Unusually, patients with Mycoplasma pne umoniae infection may display extra-pulmonary features, e.g. erythema multi- forma or other skin rashes in 25%, neurological signs in around 5%. No combination of clinical features a llows a con \201 dent pre- diction of the microbiological etiology. Infection with Mycopla sma pneumoniae, Legionella spp., Chlamydophila psit- taci or Coxiella burnetii generally in volves younger patients. 0 16 \200\22324 25 \200\22334 35 \200\22344 45 \200\22354 55 \200\22364 65 \200\22374 75 \200 \22384 85 \200\22394 >=95 Age range Fig. 8.1.1 Pneumonia admissions to 5 hospitals in a 1 year period. Microbiology Patients seen in the community (UK): \200 Streptococcus pneumoniae (36%). \200 Viruses (13%, mostly in \202 uenza A). \200 Haemophilus in \202 uenzae (10.2%). \200 Mycoplamsa pneumoniae (1.3%). Patients seen in hospital (UK): \200 \200 \200 \200 \200 \200 \200 Streptococcus pneumoniae (39%). Chlamydophila pneumoniae (13%). Viruses (12%, mostly in \202 uenza A). Mycoplamsa pneumoniae (11%). Haemophilus in \202 uenzae (5%). Legionella pn emophilia (3.6%). Chlamydophila psittaci (2.6%). Diagnosis A CXR is required to make a con \201 dent diagnosis of CAP. In one UK community study of adults with symptoms of a lower respiratory tract infection and focal chest signs, only 39% had CXR evidence of pneumonia. Differential diagnosis \200 Organizing pneumonia. \200 Bronchoalveolar cell carcinoma. \200 Eosinophilic pneumonia. \200 Vasculitis, e.g. Wegener \200\231s granulomatosis. \200 Allergic bronchopulmonary aspergillosis. Fig. 8.1.3 Organizing pneumonia presenting as consolidation. CHAPTER 8.1 Community-acquired pneumonia 167 Cavities, pneumatoceles, pneumothoraces in Staph aureus infection. Right upper lobe involve ment with a bulging interlobar \201 ssure in Klebsiella pneumoniae infection. Mediastinal lymphadenopathy in Mycoplasma pneumo- niae infection. AUTHOR \200\231S TIP \200 \200 \200 \200 \200 \200 Hotel stay in last 14 days \200\223 Legionella sp infection? Lambing or calving season \200\223 Q fever? Pet bird at home \200\223 Chlamydophila psittaci? Flu-like illness initi ally \200\223 Staphylococcus aureus? Travel to East Asia, very ill - Burkholderia pseudoma llei? Necrotising pneumonia, very ill \200\223 Staphylococcus aureus? Underlying structura l lung disease \200\223 Pseudomonas aeruginosa? Cluster of cases \200\223 outbreak? CT scanning is more sensitive than CXR for detecting the presence of consolidation. However , the clinical signi \201 - cance of CT abnormalities consistent with pneumonia in patient s with a normal CXR is unclear. Complete resolution of the CXR changes of pneumonia occurre d in 73% of cases at 6 weeks in one study. Resolution is generally slower in older patients , those with multilobar involvement and in legionella pneumonia. Investigations CRP A raised level of CRP is a more sensitive marker of pneu- monia than a r aised white cell count. In one study, all patients with CAP had a CRP of >50mg/l. Failure o f the CRP to fall by 50% within 4 days suggests treatment failure or the development of com plications. Further reading BTS Guidelines for the Management of Community Acquired Pneumonia in Adults. Thorax 2001; 56 Suppl 4: IV1 \200\22364. Campbell SG, Marrie TJ, Anstey R, et al.The contribution of blood cultures to the clinical management of adult patients admitted to the hospital with community-acquired pneumonia: a prospective observational study. Chest 2003; 123(4): 1142 \200\22350. Microbiological tests A full range of microbiological tests should be performed on patients admitted to hospital with severe CAP. This includes: \200 \200 \200 \200 \200 Jokinen C, Heiskanen L, Juvonen H, et al. Incidence of community- acquired pneumonia in the population of four municipalities in eastern Finland. Am J Epid 1993; 137(9): 977 \200\223 988. Lim WS, Macfarlane JT, Boswell TC, et al. Study of community acquired pneumonia etiology (S CAPA) in adults admitted to hospital: implications for management guidelines. Thorax 2001; 56(4): 296 \200\223301. Blood for culture and sensitivity. Sputum for culture and sensitivity. Urine for pneumococc al antigen. Urine for legionella antigen. Blood for serological tests for Mycoplasma pneumo niae, Chlamydophila spp. Legionella spp. Coxiella burnetti. Loeb M. Pneumonia in the elderly. Curr Opin Infect Dis 2004; 17(2): 127 \200\22330. Marston BJ, Plouffe JF, File TM, Jr., et al. Incidence of community- acquired pneumonia req uiring hospitalization. Results of a popu- lation-based active sur veillance Study in Ohio. The Community-Based Pneumonia Incidence Study Group. Archives of Internal Medicine 1997; 1 57(15): 1709 \200\2231718. Preferably, all samples for culture and sensitivity should be collected prior to administra tion of antibiotics. In patients with non-severe CAP, the yield from routine microbiologica l tests including blood and sputum cultures has been found to be low (<15%). Evidence of an improve- ment in clinical outcome consequent on microbiological testing in patients with n on-severe CAP and no co-morbid illness is lacking. Therefore, microbiological testing in no n- severe CAP should be guided by patient and health resource characteristics. Mittl RL, Jr., Schwab RJ, Duchin JS, et al. Radiographic resolution of community-acquired p neumonia. Am J Respir Crit Care Med 1994; 149(3 Pt 1): 630 \200\2235. Morgan M. Staphylococcus aureus, Panton-Valentine leukocidin, and necrotising pneumonia. Bmj 2005; 331(7520): 793 \200\2234. Smith RP, Lipworth BJ. C-reactive protein in simple community- acquired pneumonia. Chest 1995; 107(4): 1028 \200\2231031. Woodhead MA, Macfarlane JT, McCracken JS, et al. Prospective study of the etiology and outc ome of pneumonia in the com- munity. Lancet 1987; 1(8534): 671 \200\223674. AUTHOR \200\231S TIP Legionella and pneumococcal urinary antigen tests may remain positive for many weeks following infection. Radiological tests There are no features on CXR that allow a con \201 dent prediction of t he microbiological etiology. Nevertheless, certain patterns have been described: \200 Multilobar involvement in bacteraemic pneumococcal infection (more commonly than in non-bac teraemic pneumococcal infection). W-S LIM 168 8.1 \200\223 continued Community acquired pneumonia: severity assessment and antibiotic ma nagement Severity assessment An accurate assessment of disease severity is fundamental to the manage ment of CAP. The 2 most widely studied and used severity assessment tools in CAP are the Pn eumonia Severity Index (PSI) and the CURB65 score. Both these tools stratify patients accor ding to risk of mortality. The PSI requires the calculation of an index (range 70 \200\2233 00) from 20 parameters derived from patient demo- graphics, clinical \201 ndings and inve stigations. The practical simplicity of the CURB65 score is its main advantage over the PSI . CURB65 score \200\223 score 1 point for each parameter present: \200 \200 \200 \200 16.0% 14.0% 12.0% Penicillin resistance Tetracycline resistance Erythromycin resistance s e t a r 10.0% e c n a t s i s e R 8.0% 6.0% 4.0% 2.0% 0.0% 1999 2001 2003 Year 1997 2005