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Purpose: To determine inter-rater reliability of sarcoidosis-related computed tomography (CT) findings that can be used for scoring of thoracic sarcoidosis. Materials and methods: CT images of 51 patients with sarcoidosis were scored by five chest radiologists for various abnormal CT findings (22 in total) encountered in thoracic sarcoidosis. Using intra-class correlation coefficient (ICC) analysis, inter-rater reliability was analysed and reported according to the Guidelines for Reporting Reliability and Agreement Studies (GRRAS) criteria. A pre-specified sub-analysis was performed to investigate the effect of training. Scoring was trained in a distinct set of 15 scans in which all abnormal CT findings were represented. Results: Median age of the 51 patients (36 men, 70 %) was 43 years (range 26 - 64 years). All radiographic stages were present in this group. ICC ranged from 0.91 for honeycombing to 0.11 for nodular margin (sharp versus ill-defined). The ICC was above 0.60 in 13 of the 22 abnormal findings. Sub-analysis for the best-trained observers demonstrated an ICC improvement for all abnormal findings and values above 0.60 for 16 of the 22 abnormalities. Conclusions: In our cohort, reliability between raters was acceptable for 16 thoracic sarcoidosis-related abnormal CT findings. Key Points: • Thoracic sarcoidosis is common; knowledge on reliability of CT scoring is limited. • Scoring CT abnormalities in pulmonary sarcoidosis can achieve good inter-rater agreement. • CT scoring validation in thoracic sarcoidosis is important for diagnostic and prognostic studies. [ABSTRACT FROM AUTHOR]

Mannose-binding lectin ( MBL)-deficiency is associated with an increased susceptibility to pneumococcal infections and other forms of disease. Pneumococcal vaccination is recommended in MBL-deficient patients with recurrent respiratory tract infections ( RRTI). The response to pneumococcal vaccination in MBL-deficient individuals has not yet been studied in detail. An impaired response to pneumococcal polysaccharides in MBL-deficient patients might explain the association between MBL deficiency and pneumococcal infections. This study investigates the antibody response to pneumococcal vaccination in MBL-deficient adult patients with RRTI. Furthermore, we investigated whether there was a difference in clinical presentation between MBL-deficient and -sufficient patients with RRTI. Eighteen MBL-deficient and 63 MBL-sufficient adult patients with RRTI were all vaccinated with the 23-valent pneumococcal polysaccharide vaccine and antibodies to 14 pneumococcal serotypes were measured on a Luminex platform. There were no differences observed in the response to pneumococcal vaccination between MBL-sufficient and -deficient patients. Forty-three MBL-sufficient patients could be classified as responders to pneumococcal vaccination and 20 as low responders, compared to 15 responders and three low responders in the MBL-deficient patients. We found no clear difference in clinical, radiological, lung function and medication parameters between MBL-sufficient and -deficient patients. In conclusion, our study suggests that MBL-deficient adults with RRTI have a response to a pneumococcal capsular polysaccharide vaccine comparable with MBL-sufficient patients. Moreover, we did not find a clear clinical role of MBL deficiency in adults with RRTI. As MBL deficiency is associated with an increased susceptibility to pneumococcal infections, pneumococcal vaccination might be protective in MBL-deficient patients with RRTI. [ABSTRACT FROM AUTHOR]

Background: Finding phenotypes within COPD patients may prove imperative for optimizing treatment and prognosis. We hypothesized that it would be possible to discriminate emphysematous, large airway wall thickening and small airways disease dominant phenotypes. Methods: Inspiratory and expiratory CTs were performed in 1140 male smokers without or with mild COPD to quantify emphysema, airway wall thickness and air trapping. Spirometry, residual volume to total lung capacity (RV/TLC) and diffusion capacity (Kco) were measured. Dominant phenotype (emphysema, airway wall thickening or air trapping dominant) was defined as one of the respective CT measure in the upper quartile, with the other measures not in the upper quartile. Results: 573 subjects had any of the three CT measures in the upper quartile. Of these, 367 (64%) were in a single dominant group and 206 (36%) were in a mixed group. Airway wall thickening dominance was associated with younger age (p < 0.001), higher body mass index (p < 0.001), more wheezing (p < 0.05) and lower FEV1%predicted (p < 0.001). Emphysema dominant subjects had lower FEV1/FVC (p < 0.05) and Kco %predicted (p < 0.05). There was no significant difference in respiratory related hospitalizations (p = 0.09). Conclusion: CT measures can discriminate three different CT dominant groups of disease in male smokers without or with mild COPD. [ABSTRACT FROM AUTHOR]

Objectives: To determine the variation in quantitative computed tomography (CT) measures of air trapping in low-dose chest CTs of heavy smokers.Methods: We analysed 45 subjects from a lung cancer screening trial, examined by CT twice within 3 months. Inspiratory and expiratory low-dose CT was obtained using breath hold instructions. CT air trapping was defined as the percentage of voxels in expiratory CT with an attenuation below -856 HU (EXP(-856)) and the expiratory to inspiratory ratio of mean lung density (E/I-ratio(MLD)). Variation was determined using limits of agreement, defined as 1.96 times the standard deviation of the mean difference. The effect of both lung volume correction and breath hold reproducibility was determined.Results: The limits of agreement for uncorrected CT air trapping measurements were -15.0 to 11.7 % (EXP(-856)) and -9.8 to 8.0 % (E/I-ratio(MLD)). Good breath hold reproducibility significantly narrowed the limits for EXP(-856) (-10.7 to 7.5 %, P = 0.002), but not for E/I-ratio(MLD) (-9.2 to 7.9 %, P = 0.75). Statistical lung volume correction did not improve the limits for EXP(-856) (-12.5 to 8.8 %, P = 0.12) and E/I-ratio(MLD) (-7.5 to 5.8 %, P = 0.17).Conclusions: Quantitative air trapping measures on low-dose CT of heavy smokers show considerable variation on repeat CT examinations, regardless of lung volume correction or reproducible breath holds.Key Points: Computed tomography quantitatively measures small airways disease in heavy smokers. Measurements of air trapping vary considerably on repeat CT examinations. Variation remains substantial even with reproducible breath holds and lung volume correction. [ABSTRACT FROM AUTHOR]

Summary: Aim: To review the currently available literature comparing the FEV1/FVC 1/FVC <0.70 in diagnosing airflow obstruction in subjects aged >40 years. Methods: A structured MEDLINE, EMBASE and Cochrane search of English-language literature was conducted. Studies comparing prevalence rates according to the LLN and a fixed value were included. Attention was paid to the choice of the reference test or gold standard used. Results: Eighteen studies met the inclusion criteria. Sixteen studies compared the rates of subjects diagnosed with airflow obstruction by either definition of airflow obstruction without using a non-independent reference standard (level 4 studies). Using a fixed value of FEV1/FVC, an overall higher number of subjects were diagnosed with airflow obstruction that increased with age. Two studies included a follow-up phase comparing risks of either hospitalization or occurrence of respiratory symptoms and mortality (level 2b studies). Adjusted risks of hospitalization (HR 2.6) or mortality (HR 1.3) were significantly larger in subjects with an FEV1/FVC below 0.70 but above the LLN (in-between group) compared to subjects with normal lung function. Conclusion: The prevalence of spirometry-based COPD is greater when using the fixed value of FEV1/FVC in comparison to using the LLN. Based on one longitudinal study the in-between group appears to have a higher risk of hospitalization and mortality; therefore it seems that using the LLN of FEV1/FVC underestimates COPD. In absence of a gold standard of COPD longitudinal research will be necessary to determine which criterion is better and more clinically relevant. [Copyright &y& Elsevier]

Summary: Background: Since populations evolve, measurement protocols and equipment improve and analysis techniques progress, there is an ongoing need to reassess reference data for pulmonary function tests. Furthermore, reference values for total lung capacity and carbon monoxide diffusion capacity are scarcely available in children. We aimed to provide updated reference equations for most commonly used pulmonary function indices in Caucasian children. Methods: In the ‘Utrecht Pulmonary Function Reference Data Study’ we collected data in Caucasian children aged 2–18 years. We analyzed them using the ‘Generalized Additive Models for Location Scale and Shape’ (GAMLSS) statistical method. Results: Measurements of interrupter resistance (Rint) (n = 877), spirometry (n = 1042), body plethysmography (n = 723) and carbon monoxide diffusion/helium dilution (n = 543) were obtained in healthy children. Height (or the natural logarithm of height) and age (or the natural logarithm of age) were both significantly related to most outcome measures. Also sex was a significant determinant, except for RV, RV/TLC, FRCpleth, Raw0,5, Rawtot, Rint and FEF values. The application of previously published reference equations on the study population resulted in misinterpretation of pulmonary function. Conclusion: These new paediatric reference equations provide accurate estimates of the range of normality for most commonly used pulmonary function indices, resulting in less underdiagnosis and overdiagnosis of pulmonary diseases. [ABSTRACT FROM AUTHOR]

Summary: The mainstay of the diagnosis of asthma is the presence of reversible airway obstruction. Exhaled NO levels are increased in asthma, in close relationship with the amount of airway inflammation, and may be used for monitoring the disease and adjusting therapy. In this study we investigated the role of eNO as a diagnostic for asthma, compared with the FEV1-reversibility and the PC20 (20% decrease of the FEV1 in the bronchial histamine provocation test), in two independent centers, on an unselected population. ENO measurements were performed with chemoluminesence technique in one center and with an electrochemical device in the other. Only after correction for so-called nuisance factors (allergy, use of inhaled steroids, recent infection, smoking, sex and the use of nitrate food) the eNO appeared as a diagnostic with equal power as the FEV1-reversibility and the PC20. Therefore, screening for asthma in our study population, with the eNO measurement, is a simple, fast and safe strategy. [Copyright &y& Elsevier]

Summary: Purpose: To investigate impact of distribution of computed tomography (CT) emphysema on severity of airflow limitation and gas exchange impairment in current and former heavy smokers participating in a lung cancer screening trial. Materials and Methods: In total 875 current and former heavy smokers underwent baseline low-dose CT (30mAs) in our center and spirometry and diffusion capacity testing on the same day as part of the Dutch–Belgian Lung Cancer Screening Trial (NELSON). Emphysema was quantified for 872 subjects as the number of voxels with an apparent lowered X-ray attenuation coefficient. Voxels attenuated <−950HU were categorized as representing severe emphysema (ES950), while voxels attenuated between −910HU and −950HU represented moderate emphysema (ES910). Impact of distribution on severity of pulmonary function impairment was investigated with logistic regression, adjusted for total amount of emphysema. Results: For ES910 an apical distribution was associated with more airflow obstruction and gas exchange impairment than a basal distribution (both p <0.01). The FEV1/FVC ratio was 1.6% (95% CI 0.42% to 2.8%) lower for apical predominance than for basal predominance, for Tlco/V A the difference was 0.12% (95% CI 0.076–0.15%). Distribution of ES950 had no impact on FEV1/FVC ratio, while an apical distribution was associated with a 0.076% (95% CI 0.038–0.11%) lower Tlco/V A (p <0.001). Conclusion: In a heavy smoking population, an apical distribution is associated with more severe gas exchange impairment than a basal distribution; for moderate emphysema it is also associated with a lower FEV1/FVC ratio. However, differences are small, and likely clinically irrelevant. [Copyright &y& Elsevier]

Summary: The diffusion capacity for nitric oxide (DLNO) is independent of pulmonary capillary blood volume and equals the membrane diffusing capacity. Therefore the DLNO could be more sensitive in detecting alveolar destruction than the DLCO. We measured flow-volumes curves, DLNO, DLCO, the transfer coefficients KNO (DLNO/VA) and KCO (DLCO/VA) and performed computed tomography (CT) scans in 263 randomly selected heavy smokers. Subjects with areas ≥1% of the total lung volume showing an attenuation <−950 Hounsfield Units were considered to have emphysema. In 36 subjects emphysema was diagnosed with CT, a low KNO was present in 94 subjects, and in 95 subjects a FEV1/FVC ratio <70% was seen. The area under the ROC curve for detection CT-based emphysema was 0.894 for the KNO, 0.822 for the KCO and 0.795 for FEV1/FVC, meaning that the KNO has a slightly higher sensitivity to detect emphysema than the KCO and FEV1/FVC. The positive predictive value of KNO however was low (34.7%), while the negative predictive value of KNO was very high (98.2%), indicating an emphysema exclusion test. The DLNO/DLCO ratio is significantly higher in the study group compared to normal subjects. [Copyright &y& Elsevier]

We compared interexamination variability of CT lung nodule volumetry with six currently available semi-automated software packages to determine the minimum change needed to detect the growth of solid lung nodules. We had ethics committee approval. To simulate a follow-up examination with zero growth, we performed two low-dose unenhanced CT scans in 20 patients referred for pulmonary metastases. Between examinations, patients got off and on the table. Volumes of all pulmonary nodules were determined on both examinations using six nodule evaluation software packages. Variability (upper limit of the 95% confidence interval of the Bland-Altman plot) was calculated for nodules for which segmentation was visually rated as adequate. We evaluated 214 nodules (mean diameter 10.9 mm, range 3.3 mm-30.0 mm). Software packages provided adequate segmentation in 71% to 86% of nodules (p < 0.001). In case of adequate segmentation, variability in volumetry between scans ranged from 16.4% to 22.3% for the various software packages. Variability with five to six software packages was significantly less for nodules >or=8 mm in diameter (range 12.9%-17.1%) than for nodules <8 mm (range 18.5%-25.6%). Segmented volumes of each package were compared to each of the other packages. Systematic volume differences were detected in 11/15 comparisons. This hampers comparison of nodule volumes between software packages. [ABSTRACT FROM AUTHOR]

Background: The role of carotid surgery for the management of restenosis after carotid endarterectomy (CEA) is challenged by carotid artery stenting (CAS). We reviewed redo CEA in a consecutive series of patients to determine the safety, durability, and long-term benefit associated with repeat surgical treatment for restenosis. Methods: A consecutive series of 73 redo procedures in 72 patients (57% men) with a mean age 66 years (range, 49-81 years) was analyzed. The mean interval between prior CEA and redo CEA was 53 months (range, 8-192 months). Operative indications included symptomatic restenosis in 28 patients (38%). A patch angioplasty was performed in 62 patients (85%). The main outcome measures included perioperative and late stroke and death, and the development of secondary restenosis. Results: There were no perioperative deaths or strokes. During a mean follow-up of 52 months (range, 12-144 months), the Kaplan-Meier cumulative survival was 85% at 5 years. At 5 years, the cumulative rate of freedom from all strokes was 98%, and the freedom from ipsilateral stroke was 100%. After secondary procedures, re-recurrent stenosis ≥50% occurred in 10 patients (13.7%). The cumulative freedom from re-restenosis (≥50%) was 85% at 5 years. Five patients (7%) received tertiary carotid reconstructions. Conclusion: Repeat CEA for recurrent stenosis can be performed safely with excellent long-term protection from stroke. These data provide a standard against which the results of CAS can be compared. [Copyright &y& Elsevier]

What is already known about this subject • For asthmatic adults, bronchodilators with a MMAD between 3 and 6 µm were shown to give the best improvement in lung function and the least systemic side-effects. • It is not known, however, what is the most efficacious particle size for inhaled steroids in asthmatic adults. Clinical efficacy and systemic side-effects of inhaled steroids should be measured to define the optimal particle size. What this study adds • Our study investigated the systemic absorption of inhaled steroids. We found that a particle size of 2.5 µm and 4.5 µm gave a higher pulmonary bioavailability compared with the 1.5 µm monodisperse aerosols in adults with mild asthma and therefore were more likely to elicit systemic adverse effects. Aims For optimal efficacy, antiasthma drugs should be delivered to the desired region in the airways. To date, the optimal particle size for steroids in adults is not known. The aim of the study was to evaluate the pulmonary bioavailability for inhaled beclomethasone dipropionate (BDP) aerosols of different particle sizes. Methods In a randomized single-blind crossover trial, 10 mild asthmatic patients inhaled monodisperse BDP aerosols with mass median aerodynamic diameters (MMADs) of 1.5, 2.5 and 4.5 µm. Gastrointestinal absorption was blocked by activated charcoal. Plasma concentrations of 17-beclomethasone monopropionate (17-BMP) were measured by liquid chromatography plus mass spectrometry. Results Aerosols with MMADs of 1.5 µm, 2.5 µm, and 4.5 µm gave mean maximum concentrations ( C max) of 17-BMP of 475 pg ml−1, 1300 pg ml−1, and 1161 pg ml−1, respectively. The area under the curve (AUC) values of 17-BMP for MMADs of 1.5 µm, 2.5 µm, and 4.5 µm were 825 pg ml−1 h, 2629 pg ml−1 h, and 2276 pg ml−1 h, respectively. The mean terminal half-time of 17-BMP for all three aerosol sizes was around 1.5 h. Conclusions Monodisperse BDP aerosols with a MMAD of 1.5 µm gave two-three fold lower values for C max and AUC than those with MMADs of 2.5 and 4.5 µm. [ABSTRACT FROM AUTHOR]

Summary: Nitric oxide (NO) has a much stronger affinity for hemoglobin than carbon monoxide (CO); therefore, the DLNO (diffusing capacity for NO) is less influenced by changes in capillary blood volume than the DLCO (diffusing capacity for CO), and represents the true membrane diffusing capacity. We measured the combined single breath DLNO/DLCO in 124 healthy subjects, and generated reference equations for the DLNO and K NO. In a subset of 21 subjects the measurements were performed on different inspiratory levels. The reference equation for DLNO in females is and for males ). Reference equations for K NO in females is and for males . The K CO (DLCO/V A) increases when V A (alveolar volume) decreases, probably due to an increase of blood volume per unit lung volume. The DLNO was much stronger related to the V A, the K NO was almost independent of V A. Because of the relative independence of the K NO on V A, the K NO appears to be a much better index for the diffusion capacity per unit lung volume (transfer coefficient) than the K CO. [Copyright &y& Elsevier]

Background: The alveolar volume (VA), determined by single-breath helium dilution, is a measure for the total lung capacity (TLC) that is very sensitive to ventilatory disturbances. In chronic obstructive pulmonary disease (COPD), the emphysematous lung parts are less accessible to test gas; therefore, the VA is smaller than TLC measured by multiple-breath helium dilution (TLCHe). Objectives: The aim of this study was to investigate whether the VA represents the nonemphysematous lung parts. Methods: We measured VA as part of the diffusing capacity for carbon monoxide (DLCO), TLCHe and spirometry in 50 patients with COPD. High-resolution computed tomography (HRCT) scans of all subjects were analyzed with the density mask method, where parts with an attenuation of less than –950 Hounsfield units were considered as emphysematous. Results: A strong correlation was observed between the VA (mean 5.2 liters) and nonemphysematous HRCT lung volume (mean 5.2 liters, r2 = 0.9) and between the TLCHe (mean 6.6 liters) and total HRCT lung volume (mean 6.4 liters, r2 = 0.9). Bland-Altman plots showed considerable disagreement between the VA and the nonemphysematous HRCT lung volume. A weak correlation between the forced expiratory volume in 1 s (mean 46% predicted) and DLCO (mean 46% predicted) versus the HRCT emphysema ratio (nonemphysematous/total HRCT lung volume) was observed (r2 = 0.3 and 0.3, respectively). Conclusion: We concluded that the VA correlates with the nonemphysematous HRCT lung volume, although the two measurements are not equivalent, possibly due to technical factors. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary: Aim of the study: The diffusion capacity of the lung for carbon monoxide (DLCO) is an important tool in the diagnosis and follow-up of patients with pulmonary diseases. In case of a decreased DLCO the K CO, defined as DLCO/V A (V A is alveolar volume), can differentiate between normal alveolocapillary membrane (normal K CO) and abnormal alveolocapillary membrane (low K CO). The latter category consists of decreased surface of the membrane, increased thickness or decreased perfusion of ventilated alveoli. The V A/TLC (TLC is total lung capacity determined by whole body plethysmography) can partially differentiate between these categories. The aim of this study was to investigate the diagnostic value of the specific diffusion disturbances, which can be constructed by combining the DLCO, K CO and V A/TLC. Methods: In 460 patients the diagnosis made by clinicians were fitted into five diagnostic categories: asthma, chronic obstructive pulmonary disease (COPD), treatment effects of haematologic malignancies, heart failure and diffuse parenchymal lung diseases (DPLD). These categories were linked to the pattern of diffusion disturbance. Results: Almost all patients with asthma have a normal DLCO, most patients in the other groups do not have the expected pattern of diffusion disturbance, especially in the group with DPLD a bad match is observed. Conclusion: In this study the pattern of diffusion disturbance is of limited use in establishing a diagnosis. The use of the K CO next to the DLCO has no additional diagnostic value. Regional ventilation–perfusion inequality probably forms an important underlying mechanism of decreased DLCO. [Copyright &y& Elsevier]

Background: The diffusion capacity of the lung for nitric oxide (DLNO) is supposed to reflect the properties of the alveolocapillary membrane better than the diffusion capacity of the lung for carbon monoxide (DLCO), due to a much stronger binding of NO to haemoglobin (Hb). Objectives: The aim of this study was to investigate the effect of Hb concentration on the DLNO. Methods: The DLNO and DLCO (single-breath method) were measured in 10 anaemic patients before and shortly after red cell transfusion. Results: The mean increase in Hb concentration was 2.6 g/dl. Whereas DLCO increased as predicted by the reference equations, the DLNO did not change: mean DLCO rose from 13.6 to 16.5 ml/min/mm Hg (increase of 122%), mean DLCO corrected for Hb rose from 18.8 to 19.3 ml/min/mm Hg (103%) and mean DLNO rose from 75.6 to 77.8 ml/min/mm Hg (103%). Conclusion: The DLNO is not influenced by Hb concentration. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary: Inflammatory processes in the lung can or will elicit oxidative stress. The degree of oxidative stress can be determined by measuring hydrogen peroxide (H2O2) concentration in exhaled breath condensate (EBC) but the methods to measure H2O2 are all rather time consuming and only reliable and/or accurate in the hand of skilled technicians in a dedicated laboratory. We tested a new commercial device (Ecocheck™), developed to offer a less time-consuming method to measure H2O2. We validated this new method according the NCCLS EP10-A2 protocol. The validation shows that the imprecision in the low range is high (28.4%) and declines with higher concentrations of H2O2 (up to 6.6%). The Ecocheck™ is “an easy to use” measuring device for routine measurements getting quick results without the need for skilled technicians to determine H2O2 concentrations. [Copyright &y& Elsevier]

Summary: Restrictive lung disease comes in two major categories: (1) intrapulmonary (=parenchymal) disease caused by fibrotic reactions or (2) extrapulmonary (=compression), like in heart failure. In the first category the conducting airways, tethered in stiffened structures, are less likely to be compressed during forceful expiration and expiratory flows hence are expected to remain high. This could serve as a cheap and easy diagnostic, avoiding more complicated measures. A database was build containing 624 patients suffering from either intra- and extrapulmonary disease. The flow–volume curve indices of restrictive patients (with a total lung capacity <−1.96 sd of reference) were compared and it was shown that in primary fibrotic disease and in leukaemia, indeed, the PEF and MEF75/50/25 were significantly higher compared to the heart failure group (). The diabetes mellitus vs. heart failure differences were much less (). The area under the ROC to discriminate extra- from intrapulmonary disease was a low 0.607 and 0.606 for the PEF and MEF75, respectively. For the peakflow an optimal cut-off point was found at 65.8% of the reference value. The positive/negative predictive value of a peakflow <65.8% to detect extrapulmonary disease was 30.1% and 82.2%, respectively. [Copyright &y& Elsevier]

BACKGROUND: Despite improvements of the heart-lung machine (HLM), oxidative stress and subsequent damage to the alveolar capillary membrane still occur after conventional on-pump coronary artery bypass graft (CCABG) surgery. In an attempt to further improve the conventional HLM, a mini-extracorporeal circuit (MECC) was introduced. This new concept is based on minimal volume shifts. The extent of alveolar injury that is associated with this new technique is unknown. The lung-specific biomarkers Clara-cell 16 (CC16) and KL-6 are applied in this study to quantify alveolar dysfunction in both techniques. METHODS: In a prospective observational setting, the concentrations of CC16 and KL-6 were measured during and after 10 consecutive CCABG operations and 10 consecutive coronary artery bypass graft (CABG) operations using MECC (MCABGs). These pneumoproteins were measured after the induction of anesthesia, before clamping of the ascending aorta, after unclamping of the aorta, on arrival to the ICU, and on the following days until discharge. Quantification of the differences of KL-6 and CC16 leakage through the alveolar membranes between the two techniques was realized by calculation of the Student t test. Perioperative and postoperative shunt fractions and clinical observations were monitored simultaneously. The potential value of pneumoproteins as biomarkers for quantification of alveolar permeability during CABG surgery was tested. RESULTS: Significantly reduced concentrations of CC16 were found early after MCABG as compared to CCABG surgery (p = 0.033). KL-6 showed no consistent pattern during both treatment modalities. Early after CCABG surgery, shunt fractions tended to show reduced oxygen transport over the alveolar membrane as compared to MCABG surgery. CONCLUSION: CC16 appears to be a useful biomarker for alveolar permeability during CABG surgery. Injury of the alveolar capillary membrane appears significantly reduced during MCABG surgery. Consistently early postoperative alveolar shunt fractions showed an increased value in CCABG compared to MCABG surgery in the early postoperative phase. Further randomized studies need to confirm the value of CC16 as marker in monitoring alveolar capillary damage during coronary bypass grafting. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to compare the Multistage Liquid Impinger (MSLI) and the Andersen Cascade Impactor (ACI) with respect to their power to predict differences in side effects of salbutamol delivered by a dry powder inhaler. Three preparations with the same nominal dose and the same inhaler device but generating aerosols with different aerodynamic particle size distributions were administered to six healthy volunteers in a randomized, placebo-controlled, four-way crossover study. Cumulative doses from 400 up to 1600μg were given. The serum potassium level (K+-serum) and the heart rate (HR) were measured at baseline and 15min after each dose. Both the MSLI and ACI showed large differences between the aerodynamic particle size distributions of the three preparations. The decrease in K+-serum revealed significant differences between the three active preparations and was significant for doses of 800μg and higher. The HR results showed differences between the active preparations only at a nominal dose of 1600μg and only for the preparation with the highest fine particle dose (FPD) compared to the other two preparations. The K+-serum appears to be a more sensitive measure for side effects than the HR. In vivo-in vitro correlations (IVIVCs) were established between the amounts of salbutamol deposited on the various cumulative impactor stages and the K+-serum. The best IVIVCs were obtained in the FPD range, resulting in correlation coefficients of at least 0.78. It is concluded that cascade impactor results in the FPD range of the MSLI as well as the ACI correlate well with the K+-serum. Cascade impactor analysis thus provides a clinically meaningful tool in the development and the quality control of salbutamol inhalation powders. [Copyright &y& Elsevier]

Previously, an association between susceptibility to sarcoidosis and a polymorphism in the interleukin (IL-18) gene (IL-18 -607A/C) has been reported in Japanese. The aim of the present study was to validate this association in a clinically well-characterized population of Dutch Caucasians. Three other polymorphisms at positions -656, -137, and 1248 were included in order to extend the mapping of the IL-18 gene and to enable the construction of haplotypes. Polymorphisms were determined using sequence-specific primers (SSPs) and polymerase chain reaction (PCR). A total of 236 individuals was studied (133 patients and 103 controls). No significant differences were observed in the distribution of the -607 and the other polymorphisms between Dutch sarcoidosis patients and controls. However, significant differences in IL-18 -607 genotype and allele frequency distributions were found between the Dutch and the Japanese. From the investigated IL-18-promoter polymorphisms, we were able to deduce four haplotypes. No differences were observed in haplotype frequencies between Dutch sarcoidosis patients and controls. In conclusion, IL-18 polymorphisms do not appear to influence the susceptibility to sarcoidosis in Dutch Caucasians. Important differences in allele frequencies were observed between Japanese and Dutch sarcoidosis patients and controls. [ABSTRACT FROM AUTHOR]

Levels of exhaled nitric oxide (eNO) are flow-dependent, and the choice of an optimal flow rate for off-line and on-line eNO measurement has raised much debate. Recently, a flow rate of 50 ml/s was recommended, but children younger than 5–6 years are not capable of stabilizing their expiratory flow at low flow rates. The power of off-line eNO values to discriminate between normal and atopic children was therefore evaluated at different exhalation flow rates. At flow rates of both 8.3 ml/s and of 350 ml/s, children (8–12 years) sensitive to house dust mite have two-fold higher eNO values (p < 0.001) as compared with children lacking such a sensitivity. The power of eNO to discriminate between normal and atopic subjects was similar at the two flow rates (no difference in AUC of receiver operation curves, p = 0.89). All children from 4.5 to 5 years of age (n = 29) could perform a single off-line exhalation manoeuvre at high (>350 ml/s) but not at low (8.3 ml/s) flow rates. At high exhalation flow rate, eNO was 7.1 ± 2.4 (mean ± SD) median, 6.5 p.p.b. with a mean variation coefficient of 5.5%. Depending on their developmental level, about half of the younger children (35–46 months of age) could perform an off-line exhalation manoeuvre at high flow rate with good reproducibility (mean variation coefficient of 6.6%). It is concluded that an exhalation flow rate of 350 ml/s is feasible to determine off-line eNO-values in children from 3.5 years of age, and that this high flow rate does not compromise the power of eNO to detect allergic disease. [ABSTRACT FROM AUTHOR]

Objective: To define prognostic parameters for patients with synchronous non-small cell lung cancer (NSCLC).Design: Retrospective study of period from 1970 through 1997.Patients: Patients with a single (n = 2,764) and synchronous NSCLC (n = 85) who underwent pulmonary resection.Methods: All tumors were classified postsurgically, and the tumors of the patients with synchronous lung cancer were staged separately. The most advanced tumor was used for comparison. Actuarial survival time was estimated, and risk factors influencing survival were evaluated. Patients who died within 30 days of surgery were excluded.Measurement and Results: Five-year survival for single NSCLC was 41% and for synchronous lung cancer it was 19%. The relative risk of death for patients with synchronous lung cancer was 1.75, compared to that for patients with single lung cancer. The most advanced tumor in synchronous cancer was a significant predictor of survival (p<0.005). The survival of patients with synchronous lung cancer in which the most advanced tumors were stage I (n = 40) and stage II (n = 27) was not different from that of patients with stage II (n = 834) and stage IIIA (n = 405) single lung cancer, respectively.Conclusion: The poorer survival of patients with synchronous NSCLC is confirmed and quantified. The stage of the most advanced tumor was the best predictor of prognosis. The prognosis of patients with synchronous NSCLC resembles the prognosis of patients with a single lung cancer of a higher stage. Upstaging in synchronous lung cancer is recommended on the basis of these observations. [ABSTRACT FROM AUTHOR]