Is distal chronic thromboembolic pulmonary hypertension treatable with PAH targeted drugs?

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition that historically has a poor outcome with supportive medical treatment. Pulmonary endarterectomy (PEA) is the treatment of choice and offers the only chance of cure. A significant proportion of patients is either not suitable due to the distal distribution of the disease or has persistent pulmonary hypertension (PH) after PEA. Despite the lack of licensed therapies for CTEPH, the similarities in pathobiology of pulmonary arterial hypertension (PAH) and CTEPH has led to the compassionate use of PAH therapies in CTEPH patients. This article reviews the pathobiology of CTEPH and summaries the available evidence for the use of PAH-targeted drugs in CTEPH.

Diagnostic testing to guide the management of chronic thromboembolic pulmonary hypertension: state of the art.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening and debilitating disease affecting up to 5% of survivors of pulmonary embolism. Diagnostic testing is important to distinguish it from other forms of pulmonary hypertension and to assess the feasibility of pulmonary endarterectomy. This review provides an up-to-date perspective on the diagnosis and assessment of the disease. Patients with CTEPH often have a history of pulmonary embolism, deep-vein thrombosis, thrombophilia, splenectomy, ventriculo-atrial shunt, inflammatory bowel disease or malignancy. Chest radiography may reveal pulmonary infarcts. CTEPH is often diagnosed as a wedge-shaped perfusion defect with normal ventilation scan during ventilation-perfusion scintigraphy, but multi-slice computed tomography angiography may be needed for differential diagnosis. Right heart catheterisation is required for diagnostic confirmation. Suitability for surgery is assessed by evaluating the number of obstructed vessels which could be disobliterated in the context of the pulmonary vascular resistance. Pulmonary vascular resistance that is out of proportion to evident obstructions is indicative of distal disease. Conventional pulmonary angiography, multi-slice computed tomography angiography and, potentially, magnetic resonance imaging can aid the decision to operate, but risk stratification systems are needed. In conclusion, CTEPH can be cured surgically, providing that patients are diagnosed and assessed using the appropriate techniques.

Clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for pulmonary arterial hypertension within their licensed indications: a systematic review and economic evaluation.

OBJECTIVE(S): To investigate the clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for the treatment of adults with pulmonary arterial hypertension (PAH) within their licensed indications. DATA SOURCES: Major electronic databases (including the Cochrane Library, MEDLINE and EMBASE) were searched up to February 2007. Further data were obtained from dossiers submitted to NICE by the manufacturers of the technologies. REVIEW METHODS: The systematic clinical and economic reviews were conducted according to accepted procedures. Model-based economic evaluations of the cost-effectiveness of the technologies from the perspective of the UK NHS and personal social services were carried out. RESULTS: In total, 20 randomised controlled trials (RCTs) were included in this assessment, mostly of 12-18 weeks duration and comparing one of the technologies added to supportive treatment with supportive treatment alone. Four published economic evaluations were identified. None produced results generalisable to the NHS. There was no consensus in the industry submissions on the most appropriate model structure for the technology assessment. Improvement in 6-minute walk distance (6MWD) was seen with intravenous epoprostenol in primary pulmonary hypertension (PPH) patients with mixed functional class (FC) (mainly III and IV, licensed indication) compared with supportive care (58 metres; 95% CI 6-110). For bosentan compared with supportive care, the pooled result for improvement in 6MWD for FCIII patients with mixed PAH (licensed indication) was 59 metres (95% CI 20-99). For inhaled iloprost, sitaxentan and sildenafil no stratified data for improvement in 6MWD were available. The odds ratio (OR) for FC deterioration at 12 weeks was 0.40 (95% CI 0.13-1.20) for intravenous epoprostenol compared with supportive care. The corresponding values for inhaled iloprost (FCIII PPH patients; licensed indication), bosentan, sitaxentan (FCIII patients with mixed PAH; licensed indication) and sildenafil (FCIII patients with mixed PAH; licensed indication) were 0.29 (95% CI 0.07-1.18), 0.21 (95% CI 0.03-1.76), 0.18 (95% CI 0.02-1.64) and [Commercial-in-confidence information has been removed] respectively. The incremental cost-effectiveness ratios (ICERs) for the technologies plus supportive care compared with supportive care alone, determined by independent economic evaluation, were 277,000 pounds/quality-adjusted life-year (QALY) for FCIII and 343,000 pounds/QALY for FCIV patients for epoprostenol, 101,000 pounds/QALY for iloprost, 27,000 pounds/QALY for bosentan and 25,000 pounds/QALY for sitaxentan. For the most part sildenafil plus supportive care was more effective and less costly than supportive care alone and therefore dominated supportive care. In the case of epoprostenol the ICERs were sensitive to the price of epoprostenol and for bosentan and sitaxentan the ICERs were sensitive to running the model over a shorter time horizon and with a lower cost of epoprostenol. Two RCTs directly compared the technologies against each other with no significant differences observed between the technologies. Combinations of technologies were investigated in four RCTs, with some showing conflicting results. CONCLUSION(S): All five technologies when added to supportive treatment and used at licensed dose(s) were more effective than supportive treatment alone in RCTs that included patients of mixed FC and types of PAH. Current evidence does not allow adequate comparisons between the technologies nor for the use of combinations of the technologies. Independent economic evaluation suggests that bosentan, sitaxentan and sildenafil may be cost-effective by standard thresholds and that iloprost and epoprostenol may not. If confirmed, the use of the most cost-effective treatment would result in a reduction in costs for the NHS. Long-term, double-blind RCTs of sufficient sample size that directly compare bosentan, sitaxentan and sildenafil, and evaluate outcomes including survival, quality of life, maintenance on treatment and impact on the use of resources for NHS and personal social services are needed.

Prognostic and aetiological factors in chronic thromboembolic pulmonary hypertension.

Several prognostic variables have previously been identified in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Specific medical conditions have also been associated with the development and prognosis of CTEPH. Using a national registry, the current authors have assessed the prognostic value of a larger number of variables and have also attempted to validate the clinical importance of previously identified aetiological factors. Baseline information for all 469 CTEPH patients diagnosed in the UK pulmonary hypertension service between January 2001 and June 2006 was collected from hospital records. Although univariate analysis confirmed the prognostic importance of pulmonary resistance, in multivariate analysis gas transfer and exercise capacity predicted pulmonary endarterectomy perioperative mortality. Cardiac index and exercise capacity independently predicted outcome in patients with nonoperable disease. Previous splenectomy was noted in 6.7% of patients, being significantly more common in patients with nonoperable than operable disease (13.7 versus 3.6%). Medical risk factors were not found to predict mortality. In a large national cohort, predictors of outcome in patients with both operable and nonoperable chronic thromboembolic pulmonary hypertension have been identified. These may be useful in planning treatment. The aetiological importance of previously identified medical risk factors has been confirmed, although the current authors were unable to validate their prognostic strength.

Current differences in referral patterns for pulmonary endarterectomy in the UK.

Pulmonary endarterectomy (PEA) surgery is the treatment of choice in surgically accessible chronic thromboembolic pulmonary hypertension and is potentially curative. The UK is served by seven specialist pulmonary hypertension centres and, consequently, there are regions which do not have a specialist unit. Since 2000, Papworth Hospital (Papworth Everard, UK) has been the sole PEA provider for the UK, offering the opportunity to study the national incidence of operable disease and give potential insight into factors that might affect geographical distribution within the UK. All 262 UK residents who underwent PEA surgery between April 2000 and May 2006 were included in the present study. The age-adjusted cumulative referral rates were compared between regions to test for uniformity. Overall, observed rates differed significantly from expected, with evidence of significant nonuniformity across the UK. The highest rates were observed in proximity to the nationally designated specialist centres and in particular in East Anglia and the West Midlands, nearest Papworth. These two regions differed by >2 x SD from the national mean rate. The present study demonstrates wide geographical variation in the number of patients referred for pulmonary endarterectomy surgery. This suggests that there may be patients who are not presently being offered this potentially curative option.

The responsiveness and validity of the CAMPHOR Utility Index.

The aim of the present study was to validate and determine the minimal important difference (MID) and responsiveness of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Utility Index, a new tool enabling cost utility analyses. CAMPHOR, 6-min walking test (6MWT) and New York Heart Association (NYHA) data for 869 pulmonary hypertension patients (545 (63%) female; mean+/-SD age 56.6+/-15.4 yrs) from three centres were analysed. Utility was correlated with 6MWT data and calculated by NYHA class to assess validity. Effect sizes were calculated for those with two CAMPHOR assessments. Distribution and anchor-based MIDs were calculated. Analyses were carried out in patients receiving bosentan in order to determine whether or not those remaining in NYHA class III following treatment improved. The Utility Index distinguished between adjacent NYHA classes and correlated with 6MWT results. CAMPHOR subscales and utility were as responsive as the 6MWT (effect sizes ranged 0.31-0.69 for the CAMPHOR and 0.16-0.34 for the 6MWT). The within-group MID for the Utility Index was estimated to be approximately 0.09. Patients remaining in NYHA class III experienced, on average, a significant improvement (CAMPHOR Utility Index and functioning), which exceeded the MID. The CAMPHOR Utility Index is valid and responsive to change. Patients can experience significant and important improvements even if they do not improve on the basis of traditional outcomes, such as NYHA functional class.

Fibrinogen Aalpha Thr312Ala polymorphism is associated with chronic thromboembolic pulmonary hypertension.

Although chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by the persistence of organised thrombus, few pro-thrombotic risk factors have been identified in subjects with the disease. The aim of the present study was to compare the prevalence of eight functionally relevant haemostatic polymorphisms between CTEPH subjects and healthy controls. Genomic DNA was isolated from 214 CTEPH subjects and 200 healthy controls, and analysed for Factor V Leiden, prothrombin guanine (G) to adenine (A) substitution at nucleotide 20210 (20210G>A), plasminogen activator inhibitor-1 4G/5G, tissue plasminogen activator 7351 cytosine (C)>thymidine (T), Factor XIII 100G>T, fibrinogen Aalpha substitution of threonine with alanine at position 312 (Thr312Ala), fibrinogen Bbeta substitution of arginine with lysine at position 448 (Arg448Lys) and fibrinogen Bbeta 455G>A polymorphisms. A significant difference was demonstrated in fibrinogen Aalpha Thr312Ala genotype and allele frequencies between CTEPH subjects and controls. The presence of the alanine allele significantly increased the risk of CTEPH. The fibrinogen Aalpha alanine 312 allele alters fibrinogen alpha-alpha chain cross-linkage and has previously been associated with both increased risk of embolisation and increased resistance to thrombolysis. An association between this polymorphism and chronic thromboembolic pulmonary hypertension, therefore, supports an embolic aetiology for this disease, and may provide a mechanism by which thrombus persists following an acute event.

Acute haemodynamic responses to inhaled nitric oxide and intravenous sildenafil in distal chronic thromboembolic pulmonary hypertension (CTEPH).

INTRODUCTION: Although surgery is the treatment of choice for CTEPH, it is not appropriate for patients with surgically inaccessible distal disease. These patients are traditionally managed supportively, but may benefit from newer, more specific vasoactive therapies. This study examines the acute haemodynamic responses to inhaled nitric oxide (iNO) and intravenous sildenafil in this patient population. METHODS: Nine patients with de novo distal CTEPH and nine with persistent pulmonary hypertension post-pulmonary endarterectomy (PEA) were enrolled. At right heart catheterisation, following baseline haemodynamic measurements, iNO was administered at 20 ppm for 10 min. Following repeat measurements, iNO was discontinued with a subsequent washout period of 10 min. Sildenafil was then administered intravenously at two doses, to achieve plasma levels equivalent to 25 mg and 50 mg orally, with further measurements obtained at the end of each infusion. RESULTS: Significant reductions in mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were demonstrated following both iNO (-4.3 mm Hg or -10.3% p=0.001 and -101 dyn/s/cm(5) or -15.6% p<0.001) and sildenafil (-7.4 mm Hg or -16.9% p<0.001 and -188.8 dyn/s/cm(5) or -25.1% p<0.001). Individual mPAP and cardiac output (CO) responses to iNO and sildenafil correlated well, but haemodynamic changes following sildenafil were consistently more marked. There was, however, no difference in effect between the two doses of sildenafil. Although sildenafil caused significant reductions in systemic vascular resistance, the net haemodynamic effect of sildenafil remained pulmonary selective. Subgroup analysis suggested that post-PEA patients were more responsive to both iNO and sildenafil than de novo patients. DISCUSSION: Although all but one patient failed to fulfil the formal haemodynamic response criteria typically used in idiopathic pulmonary arterial hypertension (IPAH), subjects displayed significant acute responses to both iNO and sildenafil suggesting that increased vascular tone forms an important component of distal CTEPH. It is possible that these acute haemodynamic responses may translate to improved clinical outcomes, and thus further long term trials of sildenafil in distal CTEPH are warranted.

Effects of nebulised iloprost on pulmonary function and gas exchange in severe pulmonary hypertension.

Nebulised iloprost is established therapy of severe pulmonary hypertension; however, the effects on the bronchoalveolar compartment have not been investigated so far. We studied the short- and long-term effects of nebulised iloprost on pulmonary function tests and gas exchange in 63 patients with severe pulmonary hypertension (idiopathic n=17, chronic thromboembolism n=15, connective tissue disease n=12, congenital heart disease n=11, respiratory diseases n=8). Patients received iloprost in increasing dose up to 140 micro g iloprost/24h via an ultrasonic nebuliser. Short-term effects were assessed before and after every nebulisation: peak expiration flow decreased in mean by 1.9% (423+/-98 to 415+/-98) and percutaneous oxygen saturation increased in mean by 0.7% (90+/-6 to 91+/-5) post-nebulisation. There were no significant differences concerning underlying diagnosis or dose of nebulised iloprost. Within 3 months, 9 patients stopped treatment due to non-compliance with frequent nebulisations (n=3), or severe side effects (n=4); 2 patients with additional obstructive lung disease developed bronchoconstriction. Long-term effects were assessed by pulmonary function tests and gas exchange parameters at baseline and after 3 months treatment. There were no significant differences after 3 months therapy neither in FEV(1), FVC, TLC, residual volume nor in diffusions capacity, SO(2) at rest and during 6 min walking test, also in respect of the underlying diseases. However, there was a significant increase in 6 min walking distance (6 MWD) after 3 months (246+/-113 to 294+/-115 m, P<0.05). In conclusion, treatment with nebulised iloprost leads to functional improvement in severe pulmonary hypertension without systematic adverse short- and long-term effects on pulmonary function test or gas exchange. Patients with additional obstructive lung disease might develop bronchoconstriction. Severe side effects leading to discontinuation of treatment occurred in 9% of patients.

Does rapid dose titration affect the hepatic safety profile of Bosentan?

RATIONALE: Bosentan, a dual endothelin receptor antagonist, has proven efficacy in pulmonary hypertension. Due to an association with hepatic dysfunction, it is typically initiated at a sub-therapeutic dose for 4 weeks before titration to a therapeutic dose. At our institution some patients have undergone rapid titration, to potentially benefit from therapy earlier. This study assesses the impact of this practice on hepatic safety. METHOD: All patients initiated on bosentan therapy before April 2005 were included. Rapidly titrated patients achieved a therapeutic dose by 3 days, whereas standard titration patients were titrated at 4 weeks. All patients were monitored with monthly liver function tests. RESULTS: 149 patients commenced bosentan, of which 55 were rapidly titrated. At baseline, the two groups were similar in age, BMI, diagnosis, 6-min walking distance, alanine aminotransferase (ALT), cardiac index and pulmonary artery pressures. The rapid group had elevated right atrial pressures (9.7 mm Hg versus 7.4 mm Hg, p = 0.016) and worse WHO functional class (p = 0.008) and included less females (31% versus 69%, p = 0.024). The incidence of hepatic dysfunction in all patients was 12.8% at 12 months. There was no statistical difference in incidence between the rapid and standard groups (4% versus 11% at 3 months, p = 0.211 and 6% versus 15% at 12 months, p = 0.219). Of all patients on bosentan, hepatic dysfunction was most significantly associated with a higher baseline ALT (p = 0.021), female sex (p = 0.003) and underlying connective tissue disease (p = 0.025). Subgroup analysis suggested these factors were not confounders when comparing rapid and standard titration. CONCLUSIONS: Rapid and standard titration of bosentan resulted in similar hepatic safety profiles. Baseline ALT, female sex and the presence of connective tissue disease increased the risk of hepatic dysfunction independent of the titration method used.

The efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension: a 1-year follow-up study.

The treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). However, many patients develop a severe progressive small vessel pulmonary arteriopathy that is inaccessible to surgical intervention and is associated with poor survival. The purpose of the present study was to evaluate the medium-term efficacy and safety of the dual endothelin receptor antagonist, bosentan, in inoperable CTEPH. Forty-seven patients with inoperable CTEPH (distal disease or persistent pulmonary hypertension following PEA) underwent evaluation after 1 yr of bosentan therapy. Outcomes included assessment of 6-min walk test (6MWT), haemodynamics and World Health Organization functional classification. Monitoring of serious adverse effects and changes in therapy was undertaken. Patients showed sustained improvements in 6MWT (49+/-8 m), functional classification, cardiac index (+0.2+/-0.07 L.min(-1).m(-2)) and total pulmonary resistance (-139+/-42 dyn.s.cm(-5)). Those patients with persisting pulmonary hypertension following PEA showed the greatest improvement. One-yr survival was 96%, and bosentan was well tolerated with only one patient developing deranged liver function. Although all patients with chronic thromboembolic pulmonary hypertension should be considered for pulmonary endarterectomy, bosentan provides an alternative medical therapy to improve function and delay the progression of this devastating disease in those in whom surgery is not suitable.

The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR): a measure of health-related quality of life and quality of life for patients with pulmonary hypertension.

OBJECTIVE: No outcome measures specific to pulmonary hypertension (PH) currently exist. The aim of the study was to develop health-related quality of life (symptoms and functioning) scales and a quality of life scale that would allow comprehensive, accurate and valid patient-reported outcome assessment in clinical studies. METHODS: The content of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) was derived from qualitative interviews conducted with 35 patients. Item reduction was based on the analysis of responses to a postal survey (n=75) and patient interviews (n=15) designed to determine face and content validity. A final postal validation study (n=91) was performed to determine reproducibility and construct validity. RESULTS: The questionnaire was well received by participants who found it to be relevant, comprehensible and quick and easy to complete. Rasch and factor analyses were conducted to ensure unidimensionality of the final CAMPHOR scales; Overall symptoms (made up of Energy, Breathlessness and Mood subscales), Functioning and Quality of life. The CAMPHOR scales had good internal consistency (alpha=0.90-0.92) and reproducibility (test-retest correlations=0.86-0.92). They also exhibited convergent, divergent and known groups validity. CONCLUSIONS: The CAMPHOR is a valuable new instrument for assessing patient-reported outcome in PH clinical trials and routine practice.

Semi-quantitative assessment of tricuspid regurgitation on contrast-enhanced multidetector CT.

AIM: To assess whether the early regurgitation of intravenous contrast medium into the inferior vena cava (IVC) and/or hepatic veins on computed tomography (CT), indicates tricuspid regurgitation (TR), and if so, whether it be used to grade severity. MATERIALS AND METHODS: We identified 86 consecutive patients that had been investigated for possible pulmonary endarterectomy at Papworth Hospital. From these, 61 patients were selected in whom CT, transthoracic echocardiography, and right heart catheterization (RHC) had been performed within 6 weeks. Using an arbitrary visual scale, the degree of TR assessed by intravenous contrast-enhanced CT was compared with echocardiography. Results were analysed using a kappa weighted statistical test. In addition, CT and echocardiographic assessments of TR severity were correlated with pulmonary artery pressure measurements obtained by RHC (Spearman's rank correlation coefficient). RESULTS: CT assessment of TR had a sensitivity of 90.4% and a specificity of 100% in detecting echocardiographic TR. For TR graded as more than trivial by echocardiography, sensitivity of CT was 100%. With respect to RHC data, the correlation between severity assessment of TR between CT and echocardiography using the Kappa weighted coefficient was 0.56 (moderately good agreement). With respect to RHC data, the correlation between mean pulmonary pressure and TR grading on CT and echocardiography was r = 0.685 (p < 0.001) and r = 0.727 (p < 0.001), respectively. CONCLUSION: Early opacification of the IVC or hepatic veins on first-pass contrast-enhanced CT almost invariably indicates TR. There is moderately good agreement between CT and echocardiographic assessment of the severity of TR. Both CT and echocardiographic grading of TR correlate well with RHC measurements of pulmonary artery pressure.

Atrial septostomy in the treatment of severe pulmonary arterial hypertension.

BACKGROUND: Atrial septostomy (AS) may improve symptoms and haemodynamics in patients with severe pulmonary arterial hypertension (PAH). METHODS: Twenty AS performed in 17 patients with severe progressive PAH (13 primary pulmonary hypertension, two collagen vascular disease, one thromboembolic disease, one vaso-occlusive disease) were analysed. Seven patients were in NYHA class III and 10 in NYHA IV. Fifteen patients were on long term prostanoid treatment. AS was performed under fluoroscopy using graded balloon technique. RESULTS: AS improved clinical symptoms and increased the cardiac index from 1.8 to 2.2 l/min/m(2) and systemic oxygen transport from 263.2 to 329.6 ml/min/m(2) (p<0.001). Procedure related complications included one non-fatal atrial puncture and one unsuccessful septal puncture. Four patients died within 1 week of surgery from uncontrolled tachyarrhythmia (n=1), severe hypoxaemia (n=1), and multiorgan failure (n=2). One further patient died after voluntarily discontinuing renal dialysis. Twelve patients are alive 5-17 months after the operation with five patients undergoing heart-lung transplantation. There were no differences in haemodynamic and functional parameters between the non-survivors and the mid term survivors. However, the non-survivors were significantly older (52 v 36 years, p<0.01) and had a significantly lower creatinine clearance rate (70 ml/min v 48 ml/min, p<0.05). CONCLUSION: Atrial septostomy improves clinical symptoms, cardiac index, and systemic oxygen transport and has the potential to influence the prognosis in selected cases of severe PAH.

Role of computed tomographic scanning of the thorax prior to bronchoscopy in the investigation of suspected lung cancer.

BACKGROUND: Fibreoptic bronchoscopy (FOB) is the usual initial investigation of choice in patients with suspected endobronchial carcinoma, but it is often non-diagnostic. Once a positive diagnosis has been made, many patients undergo staging by computed tomographic (CT) scanning to assess the extent of the disease and its suitability for radical treatment. To determine whether initial CT scanning before FOB is a cost effective way of reducing subsequent unnecessary or unhelpful invasive diagnostic procedures, a study was undertaken in 171 patients with suspected endobronchial carcinoma. METHODS: A randomised two group study was performed with all patients undergoing an initial CT staging scan. In group A the CT scans were reviewed before FOB, allowing cancellation or a change to an alternative invasive procedure if considered appropriate. In group B all patients proceeded to FOB with the bronchoscopist blinded to the result of the CT scan until after the procedure. RESULTS: In group A six of 90 patients (7%) required no further investigations as the CT scan was either normal, consistent with benign disease, or consistent with widespread metastatic disease. Of the remainder, bronchoscopy was diagnostic in 50 of 68 (73%) in group A compared with 44 of 81 (54%) in group B (p = 0.015). Overall, a positive diagnosis was made after a single invasive investigation in 64 of 84 patients (76%) in group A compared with only 45 of 81 patients (55%) in group B (p = 0.005). Only seven of 90 patients (8%) in group A required more than one invasive investigation compared with 15 of 81 patients (18.5%) in group B. In patients with malignancy, bronchoscopy was more likely to be diagnostic in group A (50 of 56 patients (89%)) than in group B (44 of 62 (71%); p = 0. 012), and the diagnosis was more frequently made on the initial invasive investigation (group A, 63 of 70 (90%); group B, 44 of 62 (71%); p = 0.004). Because of the lower number of invasive procedures performed in group A than in group B, the cost of performing CT scans before FOB in all patients in group A would have equated to a projected cost of performing CT scans in 60% of patients after FOB in group B. CONCLUSIONS: Performing initial CT thoracic scans before bronchoscopy in patients with suspected endobronchial malignancy is a cost effective way of improving diagnostic yield from invasive diagnostic procedures and occasionally may obviate the need for any further investigation.