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Objectives: Intraductal Papillary Mucinous Neoplasms (IPMNs) are associated with risk of pancreatic ductal adenocarcinoma (PDAC). It is unclear if an IPMN in individuals at high risk of PDAC should be considered as a positive screening result or as an incidental finding. Stratified Familial Pancreatic Cancer (FPC) populations were used to determine if IPMN risk is linked to familial risk of PDAC.Methods: This is a cohort study of 321 individuals from 258 kindreds suspected of being FPC and undergoing secondary screening for PDAC through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Computerised tomography, endoscopic ultrasound of the pancreas and magnetic resonance imaging were used. The risk of being a carrier of a dominant mutation predisposing to pancreatic cancer was stratified into three even categories (low, medium and high) based on: Mendelian probability, the number of PDAC cases and the number of people at risk in a kindred.Results: There was a median (interquartile range, IQR) follow-up of 2 (0-5) years and a median (IQR) number of investigations per participant of 4 (2-6). One PDAC, two low-grade neuroendocrine tumours and 41 cystic lesions were identified, including 23 IPMN (22 branch-duct, BD). The PDAC case occurred in the top 10% of risk, the BD-IPMN cases were evenly distributed amongst risk categories: low (6/107), medium (10/107) and high (6/107) (P=0.63).Conclusions: The risk of finding BD-IPMN was independent of genetic predisposition and so they should be managed according to guidelines for incidental finding of IPMN

Background: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. Methods: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). Results: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). Conclusion: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.

BackgroundSurgery followed by chemotherapy is the primary modality of cure for patients with resectable pancreatic cancer but is associated with significant morbidity. The aim of the present study was to evaluate the role of cardiopulmonary exercise testing (CPET) in predicting post-operative adverse events and fitness for chemotherapy after major pancreatic surgery.MethodsPatients who underwent a pancreaticoduodenectomy or total pancreatectomy for pancreatic head lesions and had undergone pre-operative CPET were included in this retrospective study. Data on patient demographics, comorbidity and results of pre-operative evaluation were collected. Post-operative adverse events, hospital stay and receipt of adjuvant therapy were outcome measures.ResultsOne hundred patients were included. Patients with an anaerobic threshold less than 10ml/kg/min had a significantly greater incidence of a post-operative pancreatic fistula [International Study Group for Pancreatic Surgery (ISGPS) Grades A–C, 35.4% versus 16%, P = 0.028] and major intra-abdominal abscesses [Clavien–Dindo (CD) Grades III–V, 22.4% versus 7.8%, P = 0.042] and were less likely to receive adjuvant therapy [hazard ratio (HR) 6.30, 95% confidence interval (CI) 1.25–31.75, P = 0.026]. A low anaerobic threshold was also associated with a prolonged hospital stay (median 20 versus 14 days, P = 0.005) but not with other adverse events.DiscussionCPET predicts a post-operative pancreatic fistula, major intra-abdominal abscesses as well as length of hospital stay after major pancreatic surgery. Patients with a low anaerobic threshold are less likely to receive adjuvant therapy.

Aims:To characterise the spectrum of nasal symptomatology and nasendoscopic abnormalities seen in patients attending an asthma clinic, and to relate these symptoms to the likelihood of finding nasendoscopic abnormalities which merit treatment.Methods:Forty-three patients attending a problem asthma clinic were enrolled in an observational study. Cardinal nasal symptoms – obstruction, congestion, hyposmia, rhinorrhoea, sneezing, epistaxis or other symptoms – were graded as none (zero), mild (one), moderate (two) or severe (three), giving a maximum nasal symptom score of 21. Asthma symptoms and lung function were measured. Nasendoscopy was then performed.Results:Obstruction was the most common cardinal nasal symptom (seen in 15 patients), the median nasal symptom score was 5.3 (range zero to 14) and only three patients had no nasal symptoms. There was no correlation between nasal symptom score and severity of asthma symptoms or forced expiratory volume in one second. Twenty-two patients had a normal appearance on ENT examination (median nasal symptom score four). The nasendoscopic abnormalities seen comprised polyps (n = 8; median nasal symptom score five), deviated nasal septum (n = 7; median nasal symptom score four), oedematous mucosa (n = 4; median nasal symptom score seven) and other abnormalities (n = 2). Individual nasal symptoms were poor predictors of individual nasal pathologies, with hyposmia the best individual predictor of any abnormality (positive predictive value 80 per cent). The presence of a combination of symptoms increased the likelihood of any nasendoscopic abnormality, with obstruction, rhinorrhoea and hyposmia together having a positive predictive value of 100 per cent.Conclusions:Nasal symptoms are much more frequent than structural abnormalities in patients attending a problem asthma clinic. The threshold for ENT referral should be lower when the patient complains of a symptom complex including hyposmia. Furthermore, concurrent hyposmia, obstruction and rhinorrhoea should be seen as an indication for ENT referral.

Background: Within-breath reactance from forced oscillometry estimates resistance via its inspiratory component (X rs,insp ) and flow limitation via its expiratory component (X rs,exp ). Aim: To assess whether reactance can detect recovery from an exacerbation of chronic obstructive pulmonary disease (COPD). Method: 39 subjects with a COPD exacerbation were assessed on three occasions over 6 weeks using post-bronchodilator forced oscillometry, arterial blood gases, spirometry including inspiratory capacity, symptoms and health-related quality of life (HRQOL). Results: Significant improvements were seen in all spirometric variables except the ratio of forced expiratory volume in 1 s (FEV 1 ) to vital capacity, ranging in mean (SEM) size from 11.0 (2.2)% predicted for peak expiratory flow to 12.1 (2.3)% predicted for vital capacity at 6 weeks. There was an associated increase in arterial partial pressure of oxygen (PaO 2 ). There were significant mean (SEM) increases in both X rs,insp and X rs,exp (27.4 (6.7)% and 37.1 (10.0)%, respectively) but no change in oscillometry resistance (R rs ) values. Symptom scales and HRQOL scores improved. For most variables, the largest improvement occurred within the first week with spirometry having the best signal-to-noise ratio. Changes in symptoms and HRQOL correlated best with changes in FEV 1 , PaO 2 and X rs,insp . Conclusions: The physiological changes seen following an exacerbation of COPD comprised both an improvement in operating lung volumes and a reduction in airway resistance. Given the ease with which forced oscillometry can be performed in these subjects, measurements of X rs,insp and X rs,exp could be useful for tracking recovery.

Background Semiquantitative EUS-elastography has been introduced to distinguish between malignant and benign pancreatic lesions. This study investigated whether semiquantitative EUS-guided transient real time elastography increases the diagnostic accuracy for solid pancreatic lesions compared to EUS-FNA. Patients and methods This single centre prospective cohort study included all patients with solitary pancreatic lesions on EUS during one year. Patients underwent EUS-FNA and semiquantitative EUS-elastography during the same session. EUS and elastography results were compared with final diagnosis which was made on the basis of tissue samples and long-term outcome. Results 91 patients were recruited of which 68 had pancreatic malignancy, 17 showed benign disease and 6 had cystic lesions and were excluded from further analysis. Strain ratios from malignant lesions were significantly higher (24.00; 8.01–43.94 95% CI vs 44.00; 32.42–55.00 95% CI) and ROC analysis indicated optimal cut-off of 24.82 with resulting sensitivity, specificity and accuracy of 77%, 65% and 73% respectively. B-mode EUS and EUS-FNA had an accuracy for the correct diagnosis of malignant lesions of 87% and 85%. When lowering the cut-off strain ratio for elastography to 10 the sensitivity rose to 96% with specificity of 43% and accuracy of 84%, resulting in the least accurate EUS-based method. This was confirmed by pairwise comparison. Conclusion Semiquantitative EUS-elastography does not add substantial value to the EUS-based assessment of solid pancreatic lesions when compared to B-mode imaging.

Heart transplantation is an established treatment for end stage heart failure. In addition to increased life expectancy, heart transplant recipients report a remarkable improvement in symptoms and functional capacity. Exercise performance following heart transplantation, however, remains impaired even in the absence of exertional symptoms. We have assessed the response to exercise in 47 patients with cardiac failure prior to and then at yearly intervals to five years post transplantation. All patients performed incremental symptom limited exercise tests during which minute ventilation (V'E), oxygen consumption (V'O2) and carbon dioxide production (V'CO2) and heart rate (HR) were measured. Ventilatory response (V'E/V'CO2), anaerobic threshold (V'O2 AT %predicted) and heart rate response (HR/VO2) were calculated. The dead space to tidal volume ratio (VD/VT) and alveolar-arterial oxygen gradient (A-aO2) were computed from transcutaneous monitoring. Despite substantial improvement in subjective functional capacity, heart transplant recipients continue to have limited exercise performance [Maximal V'O2% predicted pre-transplant 41.3 (2.2); 1 year 48.6 (1.7), p 2 AT% 31.5 (1.1); 1 year 35.6 (1.0); respectively p2 response [24.0(1.8) vs 79.6(4.2)] were significantly reduced compared to pre-transplant values. The heart rate response remained lower compared to predicted at 5 years post-transplant although there was a significant increase compared to one year post-transplant (32.9 vs 24.0mls/bt). There was a weak but significant relationship between maximal VO2 and peak HR (0.39, pE/V'CO2 45.6 (2.5)] and decreased significantly following transplantation [1 yr 34.1 (1.3), respectively pD/VT after transplantation, it remained higher than normal [Pre VD/VT at maximum exercise 0.35 (0.02); 1 yr 0.31 (0.02); pE/VCO2 and VD/VT at two years post-transplantation with no further change at up to 5 years post transplantation [VE/VCO2 32.0 (1.0); VD/VT 0.29 (0.01)]. Although cardiac output is markedly improved after transplantation, due to chronotropic incompetence associated with denervation, its response remains subnormal and this may explain the residual abnormalities of ventilatory and gas exchange responses to exercise following transplantation.

OBJECTIVE Whole-body plethysmography is a common method of measuring pulmonary function. Although this technique provides a sensitive measure of pulmonary function, it can be problematic and unsuitable in some patients. The development of more accessible techniques would be beneficial. METHODS A prospective study was performed to validate diaphragm ultrasonography as an alternative to whole-body plethysmography in patients referred for pulmonary function testing. Diaphragm movement and position were assessed by ultrasonography after standard pulmonary function testing using whole-body plethysmography. RESULTS A wide range of lung function was observed. Standard lung volumes were as follows: total lung capacity, 5.57 +/- 1.31 L, residual volume, 2.27 +/- 0.56 L; and vital capacity, 3.30 +/- 0.98 L (mean +/- SD). The ratio of forced expiratory volume in 1 second to forced vital capacity was calculated as 0.69 +/- 0.08. Ultrasonography showed that mean diaphragm excursion values were 11.1 +/- 3.8 mm (2-dimensional), 14.7 +/- 4.1 mm during quiet breathing (M-mode), and 14.8 +/- 3.9 mm during a maximal sniff (M-mode). The velocity of diaphragm movement rose sharply during the sniff maneuver from 15.2 +/- 5.8 mm/s during quiet breathing to 104.0 +/- 33.4 mm/s. Static 2-dimensional measures of diaphragm position at the end of quiet inspiration or expiration correlated with standard measures of lung volume on plethysmography (eg, a correlation coefficient of 0.83 was obtained with end inspiration and vital capacity). All measures of diaphragm movement (whether by 2-dimensional or M-mode techniques) were poorly correlated with any lung volumes measured. CONCLUSIONS These data suggest that dynamic measurements using diaphragm ultrasonography provide a relatively poor measure of pulmonary function in relation to whole-body plethysmography.

Background/Aims: The influence of type of surgery and occurrence of post-operative complications on survival following adjuvant therapy for pancreatic cancer are uncertain. Methods: Cox proportional hazard modelling was used to investigate the influence of type of surgery and the presence of complications on survival in conjunction with clinico-pathological variables in the 550 patients of the ESPAC-1 adjuvant randomized controlled trial. Results: Standard Kausch-Whipple (KW) was performed in 282 (54%) patients, 186 (35%) had a pylorus-preserving (PP) KW, 39 (7%) had a distal pancreatectomy and 21 (4%) had a total pancreatectomy. Post-operative complications were reported in 140 (27%) patients. PP-KW patients survived longer with a median (95% CI) survival of 19.9 (17.3, 23.1) months compared to 14.8 (13.0, 16.7) for KW patients (χ2LR = 15.1, p < 0.001). KW patients were more likely however to have R1 margins (67 (24%) vs. 29 (16%), χ2 = 4.59, p = 0.032), poorly differentiated tumours (70 (26%) vs. 19 (10%), χ2 = 18.65, p < 0.001) and positive lymph nodes (165 (60%) vs. 81 (44%), χ2 = 11.32, p < 0.001). Post-operative complications did not significantly affect survival. Independent prognostic factors were tumour grade, nodal status and tumour size but not type of surgery or post-operative complications. There was a survival benefit for chemotherapy irrespective of the type of surgery or post-operative complications. Conclusions: The KW and PP-KW procedures did not significantly influence the hazard of death in the presence of tumour staging, demonstrating that ESPAC-1 surgeons showed good judgement in their choice of operation. Post-operative complications did not adversely affect the survival benefit from adjuvant chemotherapy.

The slow response characteristics of the combined transcutaneous electrode have been viewed as a major disadvantage when compared with other types of non-invasive assessment of gas exchange during exercise testing. We have previously shown that by using the highest recommended temperature of 45 degrees C to reduce response times, and combining this with an exercise protocol of gradual work load increments, that this allows changes in arterial blood gases to be closely followed by transcutaneous values. In the present study we have validated the use of a transcutaneous electrode for estimation of alveolar-arterial oxygen gradient (AaO2) and dead space to tidal volume ratio (V(D)/V(T)) during exercise, against values calculated from direct arterial blood gas analysis. One hundred measurements were made in 20 patients with various cardiopulmonary disorders who underwent exercise testing. Exercise testing was performed by bicycle ergometry with a specific protocol involving gradual work load increments at 2 min intervals. Transcutaneous gas tensions were measured by a heated combined O2 and CO2 electrode. Arterial blood was sampled at the midpoint of each stage of exercise and transcutaneous tensions noted at the end of each stage. The mean difference of the AaO2 gradient calculated from blood gas tensions obtained by the two methods was 0.14 kPa. The limits of agreement were -0.26 and 0.63 kPa. The same values for V(D)/V(T) calculated from gas tensions measured by the two methods were: mean difference 0001; limits of agreement -0.0242 and 0.0252. For both these parameters there was an even scatter around the mean value on Bland and Altman analysis. The findings of this study suggest that estimation of parameters of gas exchange using transcutaneous values during exercise testing is reliable, provided the electrode is heated to a slightly higher temperature than usual and the work load increments are gradual, allowing for the latency in the response time of the system. This system allows the assessment of the contribution of ventilation/perfusion inequality to breathlessness on exertion in patients, provided an initial arterial or ear lobe capillary sample is obtained for calibration purposes. This technique is particularly valuable in patients undergoing repeat exercise tests as it circumvents the need for arterial cannulation.

OBJECTIVES—To determine the mechanism of impairment of pulmonary transfer factor for carbon monoxide (TLCO) in heart transplant candidates, as this is the most common lung function abnormality. SETTING—Regional cardiopulmonary transplant centre. METHODS—TLCO and its components (the diffusing capacity of the alveolar-capillary membrane (DM) and the pulmonary capillary blood volume (VC)) were measured using the Roughton and Forster method and the single breath technique in 38 patients with severe chronic heart failure awaiting heart transplantation (mean age 51 years, range 19 to 61; mean left ventricular ejection fraction 12.8%). Results were compared with data from 26 normal subjects (mean age 47 years, range 27 to 62). RESULTS—Mean per cent predicted TLCO, DM, and VC were significantly reduced in patients (69.9%, 81.4%, and 80.2% of predicted, respectively) compared with controls (97.7%, 100.1%, and 102.3% of predicted, respectively, p

In contrast to the standard single-breath transfer factor for carbon monoxide ( T lCO), there are no specific guidelines or recommendations for the measurement of its components, the pulmonary capillary blood volume ( V C ) and membrane component ( D M ), by the Roughton and Forster method. Ten randomly selected heart transplant patients (three life-long non-smokers, seven ex-smokers > 1 yr, age range 24–55 years) were assessed on two occasions using either the standard or high-oxygen mixture as the first inspired gas in random order. Ten normal subjects (all non-smokers, age range 23–54 years) were assessed on two occasions using either a long protocol (30 min waiting time between repeat measurements in an individual set) or a short protocol (5 min waiting time). Two technically acceptable results of T lCO were used to derive a mean value for D M and V C for each set of measurements (Transflow, P. K. Morgan, Kent, U.K.). The different sequences of gas mixtures produced no significant differences between the values obtained in ten heart transplant patients for mean T lCO (mmol min −1 kPa −1 ) (standard first 5·13 ± 1·15, high-oxygen first 5·14 ± 1·12; limits of agreement −0·57 to 0·59 for D M or for V C . The long or short protocol produced no significant differences between the means of T lCO (mmol min −1 kPa −1 ) (long 8·0 ± 1·9, short 8·0 ± 1·9; limits agreement −0·5 to 0·5), D M or V C . This allows the development of a standard test protocol of short duration (about 40 min) making it practical for clinical use without compromising the precision or reproducibility of the results obtained.

Nineteen percent of women are habitual snorers, yet most snoring studies report only on male snorers. The aim of this study was to identify the factors responsible for habitual snoring in women. Twenty-four snorers and 16 controls were studied prospectively in a special snoring clinic. Snorers were shorter (p =.005) and heavier (p =.001), and with greater body mass index (BMI; p

The aim of the present study was to examine the relationship between the clinicopathological status, the pre- and postoperative systemic inflammatory response and survival in patients undergoing potentially curative resection for ductal adenocarcinoma of the head of the pancreas. Patients (n = 65) who underwent resection of ductal adenocarcinoma of the head of pancreas between 1993 and 2001, and had pre- and postoperative measurements of C-reactive protein, were included in the study. The majority of patients had stage III disease (International Union Against Cancer Criteria, IUCC), positive circumferential margin involvement (R1), tumour size greater than 25 mm with perineural and lymph node invasion and died within the follow-up period. On multivariate analysis, tumour size (hazard ratio (HR) 2.10, 95% confidence interval (CI) 1.20-3.68, P = 0.009), vascular invasion (HR 2.58, 95% CI 1.48-4.50, P0.001) and postoperative C-reactive protein (HR 2.00, 95% CI 1.14-3.52, P = 0.015) retained independent significance. Those patients with a postoperative C-reactive proteinor = 10 mg l(-1) had a median survival of 21.5 months compared with 8.4 months in those patients with a C-reactive protein10 mg l(-1) (P0.001). The results of the present study indicate that, in patients who have undergone potentially curative resection for ductal adenocarcinoma of the head of pancreas, the presence of a systemic inflammatory response predicts poor outcome.

The mechanism of breathlessness on exertion in patients with chronic heart failure are still not fully understood. We therefore investigated the effects of ventilatory and gas exchange abnormalities on exercise capacity in chronic heart failure. Exercise testing was performed in 30 patients with exertional breathlessness due to chronic heart failure and in 30 controls, using continuous transcutaneous blood gas monitoring. Maximal symptom-limited oxygen consumption as (V'O2) as a percentage predicted was reduced in patients (45 +/- 10%; mean +/- SD) compared to controls (87 +/- 7). The ventilatory response (minute ventilation/carbon dioxide production (V'E/V'CO2)) was significantly increased in patients compared to controls (39.9 +/- 7.7 and 25.9 +/- 3.6, respectively). The dead space to tidal volume ratio (VD/VT) was raised in patients compared to controls at rest (0.45 +/- 0.04 vs 0.35 +/- 0.02, respectively) and this persisted on exertion (0.40 +/- 0.05 in patients and 0.20 +/- 0.05 in controls). At maximal symptom-limited exercise, V'E/V'CO2 was inversely related to the % predicted V'O2 in patients, but not in controls (r = -0.62 and r = -0.24, respectively). In patients, V'E/V'CO2 was significantly correlated with VD/VT at maximum exercise (r = 0.82). Patients with chronic heart failure have a significant degree of "wasted ventilation" on exertion, which is associated with increased ventilatory response. The increased ventilatory response on exertion appears to contribute to exercise limitation in these patients.

Dysfunctional breathing (DB) is recognized as an associated problem in patients with asthma and may be identified by the Nijmegen questionnaire. We conducted an observational study to determine if breathing control therapy (BCT) improved Nijmegen scores or asthma-related quality of life in patients attending a problem asthma clinic.Nijmegen and Mini Asthma Quality of Life (Mini-AQLQ) questionnaires were completed. Patients with a positive Nijmegen (or = 23, DB) were referred for BCT and progressive exercise testing (PET) to seek confirmation of dysfunctional breathing. Follow-up questionnaire data were collected at 6 months.A total of 102 patients were studied. The total mean Nijmegen score was 26.4 (range 1-61). Those with a scoreor = 23 (DB group, n = 65, 64%) had significantly lower Mini-AQLQ (mean 2.83) than the non-DB group (n = 37, mean 4.12, 95% CI for difference 0.87, 1.87, p0.0001). There was a strong relationship between Nijmegen score and Mini-AQLQ (r = -0.63, p0.001) at baseline; 10 of 17 DB patients who completed PET showed inappropriate hyperventilation. Follow-up data, available for Nijmegen and Mini-AQLQ in 44 and 46 patients respectively, showed no significant change in either of these parameters.The strong relationship between Mini-AQLQ and Nijmegen scores and poor relationship between Nijmegen scores and PET-identified inappropriate hyperventilation suggest that a positive Nijmegen score overestimates the presence of dysfunctional breathing in patients with moderate to severe asthma. We found no evidence that a moderate intensity breathing control intervention had any impact on Nijmegen scores or asthma-related quality of life in this patient group.

Summary Background Nebulised therapy is commonly used in the management of patients with asthma and chronic obstructive pulmonary disease (COPD). There are guidelines setting out standards for maintenance of the compressor and replacement and care of consumables. This study surveys patients using nebulisers to ascertain the reported use and maintenance of the nebulisers and any side effects related to therapy. Methods An anonymous postal questionnaire, requesting information on nebuliser use and maintenance, and side effects was sent to 200 patients who had been maintained on nebuliser therapy and had been in contact with the nebuliser service at Glasgow Royal Infirmary within the last year. Results One hundred and seventeen (58.5%) questionnaires were returned completed or partially completed for analysis. The majority of patients who replied were female (median age of 69 years). The most commonly reported diagnosis was COPD (87/117); 92/117 (79%) were smokers or ex-smokers. The most commonly reported side effects associated with treatment are dry mouth, tremor and chest tightness. The responses to questions on servicing, maintenance and replacement of consumables indicate that patients comply poorly with these activities. Additionally compliance with the prescribed drug regimen occurs in less than 50% of the patient cohort. Conclusions The results of this study indicate that compliance with instructions given on the care and maintenance of home nebulisers may be suboptimal. Additionally patients reported poorer compliance than was predicted. These areas may be improved with the introduction of a new patient information leaflet.

Severe chronic heart failure (CHF) can still be associated with an annual mortality of up to 51%.1 Over the last seven years, β blockers have been conclusively shown to improve both morbidity and mortality in heart failure, even in its advanced stages.2,3 However, a recent report suggests β blocker use in CHF is still not widespread.4 This may be due to non-specialist care, perceived or actual difficulty establishing patients on this treatment, or perhaps the recollection of old teachings on the dangers of β blockade in heart failure. This study describes the experience of β blockade and its effects in patients with CHF caused by severe left ventricular systolic dysfunction (LVSD), and seeks to extend the importance of the clinical trial data into the real world. We retrospectively studied the effects of baseline β blocker use in 128 consecutive patients with advanced heart failure on their referral to the Scottish Cardiopulmonary Transplant Unit for cardiac transplantation (CTx) assessment between April 2001 and August 2002. Treatment on initial assessment was documented and subsequently optimised. Patients had their left ventricular ejection fraction (LVEF) measured by radionuclide ventriculography and, where possible, a progressive exercise test to quantify their peak oxygen uptake (Vo2). A baseline heart failure survival score (HFSS) was calculated for each patient. The primary end point was all cause mortality and the secondary end point was all cause mortality or urgent transplantation. Urgent transplantation is considered in suitable inotrope dependent patients with end stage heart failure who have an anticipated life expectancy of less than one week. Patients …

Study objectives Patients with rheumatoid arthritis (RA) have a high prevalence of pulmonary function test (PFT) abnormality, but the long-term significance of this is unknown. We performed a longitudinal study of pulmonary function in asymptomatic, nonsmoking patients with active RA requiring disease-modifying drugs. We looked for temporal change in lung function and characteristics that would predict subsequent development of PFT abnormality or respiratory symptoms. Methods In 1990, 52 patients (44 women; age range, 29 to 78 years; median, 56 years) underwent clinical assessment (drug history, RA severity, immunologic, and inflammatory markers) and PFTs (spirometry, body plethysmography, gas transfer). PFT results were expressed as standardized residuals (SRs). Thirty-eight patients were reassessed in 2000. A self-administered questionnaire was used to identify respiratory symptoms. Results The prevalence of pulmonary function abnormality was higher than expected compared with a reference population, but there was no significant increase in number over 10 years (8.7% in 1990 and 8.8% in 2000). When assessed by group means and compared with reference values, reduced diffusing capacity of the lung for carbon monoxide (Dlco) and increased ratio of residual volume (RV) to total lung capacity (TLC) [RV/TLC] were the only abnormalities to develop over the study period (mean Dlco in 2000, − 0.47 SR; 95% confidence interval [CI], – 0.91 to – 0.01; RV/TLC, 0.49 SR; 95% CI, 0.13 to 0.84). However, rates of change of pulmonary function variables were not significantly different from zero. Logistic regression did not identify any meaningful relationship between disease characteristics and PFT abnormality. Conclusions Asymptomatic patients with RA have a higher prevalence of PFT abnormality than expected, but these do not increase in number over time. We did not identify any patient or disease-specific characteristic that could predict the development of respiratory disease in patients with RA. Analysis using percentage of predicted values, rather than SRs, is misleading as it exaggerates the extent of abnormality present. Abnormal lung function is a common and probably benign finding in nonsmoking, asymptomatic patients with RA.

Background: Evaluation of fat-free mass (FFM) is becoming recognised as an important component in the assessment of clinical status and formulation of prognosis in patients with chronic obstructive pulmonary disease (COPD). Objective: The aim of this study was to determine whether potential differences in FFM estimation performed by air displacement plethysmography (ADP), bioelectrical impedance (BIE) and anthropometry (ANTHRO) would assume clinical significance. Methods: Twenty-eight patients with moderate-to-severe COPD were submitted to FFM estimation by ADP, BIE and ANTHRO. FFM was then allometrically related to peak oxygen uptake (peak v̇O2) as determined by symptom-limited incremental cycle ergometry. Results: We found that ANTHRO classified fewer patients as ‘FFM-depleted’ than the other two techniques (p < 0.05). Although mean biases of the BIE-ADP differences were close to zero, their 95% confidence limits extended as high as 5.9 kg (16%). The ANTHRO-based allometric exponents for peak v̇O2 correction of FFM, therefore, were typically higher than those obtained by the other two methods in both depleted and non-depleted patients (ANTHRO: 1.45–1.41, BIE: 0.97–1.18, ADP: 1.08–1.14, respectively). Conclusion: We conclude that between-method differences in FFM estimation can be sufficiently large to have practical implications in patients with moderate-to-severe COPD. A single method of body composition assessment, therefore, should be used for FFM estimation in these patients.

Objective: Although the decline in the pulmonary transfer factor (TLCO) following heart transplantation is well documented, the causes and mechanisms of this decline remain unknown. The aim of this study was to determine the relative contribution of each of TLCO components (the diffusing capacity of the alveolar-capillary membrane (DM), the pulmonary capillary blood volume (VC) and haemoglobin concentration) to TLCO reduction in heart transplant recipients. Methods :T L CO and its components were measured in 75 heart transplant recipients (mean age 48 years, range 19‐61) between 6 weeks and 36 months after transplantation using the Roughton and Forster method and the single-breath technique. Results were compared with data from 38 heart transplant candidates (mean age 51 years, range 34‐61) and 26 normal subjects (mean age 47 years, range 27‐62). Results: The mean percentage predicted TLCO was reduced in recipients compared to candidates (56.9 and 69.9%, respectively, P , 0:001) and both were lower than normal controls (97.7%, P , 0:001). The mean percent predicted VC was also reduced in recipients compared to candidates (52.8% vs. 80.2 (4.2)%, P , 0:001) which was also lower than normal subjects (102%, P , 0:001). DM was equally reduced in recipients and candidates (77.7 and 81.4%, respectively, Pa 0:48) compared to normal subjects (100.0%, P , 0:001). Correction for haemoglobin concentration increased TLCO in recipients to 63.5% (P , 0:001), but it remained lower than haemoglobin-corrected TLCO in candidates (71.1%, P , 0:001). In recipients, the intra-capillary resistance (1/u VC) formed 60% of the total resistance to CO transfer (1/TLCO) compared to 50% in candidates and normal subjects. Conclusions :T L CO decline following heart transplantation is due to an increase in the intra-capillary resistance, and this appears to be due to a combination of anaemia and reduced pulmonary capillary blood volume, with the diffusing capacity of the alveolar-capillary membrane remaining unchanged. q 2000 Elsevier Science B.V. All rights reserved.

Pulse oximetry has recently received attention in the dysphagia literature on account of its possible contribution to the management of neurogenic dysphagia. The present study was devised to examine whether pulse oximetry could be exploited to determine episodes of aspiration in patients with known dysphagia of neurological origin. To this end, pulse oximetry was undertaken in six patients undergoing videofluoroscopic study of swallow. Normal controls also underwent pulse oximetry during feeding. The results indicate that there is no clear-cut relationship between changes in arterial oxygenation and aspiration. Some support, however, is found for altered arterial oxygenation being associated with oral feeding in dysphagic individuals. Further research in both normal subjects and compromised individuals is required.

Objective: The pulmonary transfer factor for carbon monoxide (TL co ) has been reported to decline following heart transplantation, but the time course of this decline is not well documented. The aim of this study was to define the longitudinal changes in TL co after heart transplantation. Methods: Single breath TL co , lung volumes and expiratory flow rates were prospectively measured in 57 patients (mean age 49 years, range 19-61) before and at least once after heart transplantation. Thirty seven of the 57 patients had four post-transplant assessments which were performed at 6 weeks, 3, 6 and 12 months in 26 patients and at 12, 18, 24 and 36 months in 11 patients. Results were compared with data from 28 normal subjects (mean age 40 years, range 19-61). Results: Before transplantation there was a mild impairment of lung volumes and expiratory flow rates. At 6 weeks after transplantation, there was a further reduction in the forced expiratory volume in one second, forced vital capacity, residual volume and total lung capacity, but all of these increased in the subsequent measurements to exceed their pre-transplant values at about 1 year after transplantation. Haemoglobin-corrected TL co was also reduced before transplantation compared to normal controls (74.3% and 98.6% of predicted respectively, P < 0.001). Although TL co per unit alveolar volume (K co ) was relatively preserved in heart transplant candidates, it was still significantly lower than that of normal controls (92.6% and 105.3% of predicted respectively, P < 0.05). After transplantation, mean haemoglobin-corrected TL co and K co declined by 12% and 20% of predicted respectively) with the majority of patients having reductions greater than 10% of predicted. The decline in TL co and K co was evident at 6 weeks after transplantation with no further changes in the subsequent measurements. Conclusions: TL co is reduced in heart transplant candidates and declines further after heart transplantation despite improvement in lung volumes and airway function. The early and non-progressive nature of TL co decline suggests an aetiology exerting its effect on TL co within the first 6 weeks after transplantation.

Cardiopulmonary bypass induces respiratory dysfunction postoperatively, with activation of both the complement system and white cells implicated. This study compared the effects of bubble and membrane oxygenators for cardiopulmonary bypass in terms of respiratory dysfunction and markers of white cell activation and endothelial damage.Fifty patients undergoing cardiopulmonary bypass were randomly allocated either membrane or bubble oxygenation. Respiratory function was assessed serially by arterial oxygen tension and alveolar-arterial oxygen gradient. Complement activation was measured by serial sampling of serum C3a levels. White cell activation was assessed by serial measurement granulocyte elastase; other markers investigated were levels of thromboxane B2, von Willebrand factor and malondialdehyde. All sample measurements were made preoperatively, early and late during bypass, 4-6 h postoperatively and then on the 1st, 2nd and 6th postoperative day. All samples were corrected for haemodilution, and differences between groups tested non-parametrically.In both groups of patients there was a highly significant fall (P0.001) in arterial oxygen tension accompanied by a highly significant rise (P0.0001) in aleveolar-arterial oxygen gradient at 18 h compared to preoperative values persisting until 6 days postoperatively. Levels of C3a increased significantly in both groups at 10 min post bypass, increased further at 60 min peaking at 4-6 h post bypass. Granulocyte elastase serum levels increased significantly at 10 min postoperatively in both groups compared to control levels, remaining elevated till 48 h, but returning to control levels by 6 days. There was a small difference (P0.04) between the groups at 4-6 h only. Levels of von Willebrand factor increased significantly at 60 min post bypass in both groups, remaining elevated 6 days postoperatively. Levels of malondialdehyde increased at 10 min post bypass, remaining elevated until 6 days post bypass. Thromboxane levels showed no significant changes. For all markers measured, there were no significant differences between the groups other than those already indicated.This study demonstrated marked respiratory dysfunction, complement activation and white cell activation in patients undergoing cardiopulmonary bypass with either bubble or membrane oxygenators. There was marked variability in the response of individual patients with either oxygenation technique, but overall no significant differences between the groups.

Respiratory dysfunction is a well recognized complication of cardiopulmonary bypass. The size of the pulmonary shunt fraction is the best indicator of respiratory dysfunction but its measurement conventionally requires use of a pulmonary artery catheter to measure mixed venous oxygen content. We compared pulmonary shunt fraction, based on a non-invasive technique using a previously described mathematical model, with shunt fraction measured invasively using a pulmonary artery catheter in 22 patients undergoing elective coronary artery surgery. The mean shunt fraction measured by the invasive technique was 19·6 ± 2·0 (18·8–20·4)% of cardiac output at 24 h (± 1 sd and 90% confidence intervals) and 20·9 ± 2·9 (19·8–22·0)% of cardiac output at 44 h post-surgery. There was good agreement between the two methods of measurement. The mean difference was 0·21 percentage points with 95% confidence interval −0·01 to 0·43. The limits of agreement (−1·17 to 1·59) are small enough to be confident that the non-invasive method can be used to give the same result as that obtained using a pulmonary artery catheter. The values for shunt fractions obtained by the non-invasive technique were 19·7 ± 2·3 (18·8–20·6)% of cardiac output at 24 h and 20·7 ± 2·5 (19·7–21·6)% of cardiac output at 44 h. The non-invasive measurement of the shunt fraction provided us with a simple, practical method for following a further ten patients over an extended period of time where prolonged catheterization is impractical.

13 fire victims who required treatment after smoke inhalation underwent lung function assessment within 3 days of injury and 3 months later. Initial airways hyperreactivity improved over this period, but FEV1 and airways specific conductance did not change significantly. There was a strong correlation between exposure carboxyhaemoglobin concentration (an indicator of smoke exposure) and initial airways specific conductance (r + 0.79; p = 0.006). Airways obstruction after smoke inhalation in house fires may be more common and more persistent than is generally recognised. Early lung function tests would allow the incidence of pulmonary complications after smoke inhalation and the potential benefits of early use of inhaled antiinflammatory drugs to be assessed.

SummaryObjectiveWe wished to evaluate the effects of inhaled formoterol, a long-acting β2-adrenergic agonist, on exercise tolerance and dynamic hyperinflation (DH) in severely disabled chronic obstructive pulmonary disease (COPD) patients.DesignIn a two-period, crossover study, 21 patients with advanced COPD (FEV1=38.8±11.7% predicted, 16 patients GOLD stages III–IV) were randomly allocated to receive inhaled formoterol fumarate 12μg twice daily for 14 days followed by placebo for 14 days, or vice versa. Patients performed constant work-rate cardiopulmonary exercise tests to the limit of tolerance (Tlim) on a cycle ergometer: inspiratory capacity (IC) was obtained at rest and each minute during exercise. Baseline and transitional dyspnoea indices (BDI and TDI) were also recorded.ResultsEighteen patients completed both treatment periods. Formoterol treatment was associated with an estimated increase of 130s in Tlim compared with placebo (P=0.052): this corresponded to a 37.8% improvement over placebo (P=0.012). Enhanced exercise tolerance after bronchodilator was associated with diminished DH marked by higher inspiratory reserve and tidal volumes at isotime and exercise cessation (P

Haemodynamic studies at rest and during exercise together with radionuclide ventriculography, pulmonary function and clinical well-being assessment were evaluated in ten patients with COPD and secondary pulmonary hypertension (mean PAP 25 mm Hg), before and after 6 months therapy with pirbuterol 20 mg thrice daily. Despite the continued pharmacological action of pirbuterol on the heart and systemic circulation during peak pirbuterol levels at 6 months, no significant effect on the pulmonary circulation was observed. Seven patients reported an improvement in the level of fatigue, the partial pressure of carbon dioxide fell significantly (6.5 +/- 0.9 to 6.1 +/- 0.9 kPa: P less than 0.01) and there was a slight bronchodilator effect [forced expiratory volume in 1s (FEV1) 0.60 +/- 0.18 to 0.71 +/- 0.2 1s-1: P less than 0.02] after 6 months. The drug was generally well tolerated but three patients with pre-existing biliary tract disease developed obstructive jaundice.