Erratum to "Practical guidelines: lung transplantation in patients with cystic fibrosis".

[This corrects the article DOI: 10.1155/2014/621342.].

Measurement of shear wave velocity using acoustic radiation force impulse imaging is not hampered by previous use of ultrasound contrast agents.

PURPOSE: To assess the inter-observer reproducibility of acoustic radiation force impulse imaging (ARFI) between 2 skilled physicians and to evaluate if ultrasound contrast agents (UCA) affect the measurement of shear wave velocity (SWV) using ARFI. PATIENTS AND METHODS: 53 patients (29 males, 24 females, 59 ± 15 [22-84] years) who underwent contrast enhanced ultrasound (CEUS) examination were included. ARFI was performed on liver segment V by physicians A and B before CEUS, and by physician A within 4-6 minutes and 7-10 minutes after contrast injection. In a subgroup of 31 patients (15 males, 16 females, 57 ± 18 [22-84] years), ARFI was also performed on focal liver lesions (FLL) by physician A before CEUS, and within 4-6 minutes and 7-10 minutes after contrast injection. RESULTS: The SWV values obtained by physician A and B before CEUS yielded an intra-class correlation coefficient value of 0.913 (95% CI, 0.849-0.950). No significant differences were shown between the SWV values of liver segment V in all 53 patients and of FLL in the subgroup of 31 patients obtained before CEUS and that of within 4-6 minutes and 7-10 minutes after contrast injection (all P > 0.05). CONCLUSION: ARFI showed excellent inter-observer reproducibility between 2 skilled physicians. UCA did not affect the measurement of SWV in both liver parenchyma and FLL, at least when performed 4 minutes after the contrast injection. ARFI may become an additional tool in the differential diagnosis of FLL.

Practical guidelines: lung transplantation in patients with cystic fibrosis.

There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation.

Spectrum of viral infections in patients with cystic fibrosis.

This review explores the extensive influence of viral infections leading to chronic deterioration of lung function in patients with cystic fibrosis (CF). The mechanisms how viral agents affect the pathogenesis as well as the inflammatory and immune response of CF are discussed. Viral infections of the upper and lower respiratory tract due to viruses in CF patients and methods for diagnosis of respiratory viruses are described in detail. The importance of respiratory and non-respiratory viral agents for the pathogenesis, especially for the exacerbation of bacterial lower respiratory tract infections and course of CF, is stressed, especially emphasizing respiratory syncytial virus, influenza virus, rhinovirus, and human herpes viruses. Possible harmful effects of further viruses like adenovirus, bocavirus, coronavirus, metapneumovirus, parainfluenzavirus on the lung function of CF patients are discussed. The potential use of adenovirus-based vectors for somatic gene therapy is mentioned.

The influence of virus infections on the course of COPD.

Chronic obstructive pulmonary disease (COPD) is extensively influenced by viral infections. The mechanisms of how viral agents affect the pathogenesis and prognosis of COPD are numerous. In general, patients with infectious exacerbations are characterized by longer hospitalization periods and greater impairment of several lung function parameters than those with non-infectious exacerbations. Prodromal, clinical, and outcome parameters fail to distinguish virally from non-virally induced illnesses in cases of exacerbations. The importance of infections with respiratory and non-respiratory viral agents for pathogenesis and course of COPD is detailed. Human adenovirus, non-respiratory viruses including human immunodeficiency virus, human metapneumovirus, influenza virus, human rhinovirus, and respiratory syncytial virus are especially stressed.

Increased levels of anti-glycan antibodies in patients with cystic fibrosis.

BACKGROUND: The prevalence of Crohn's disease (CD) is increased in patients with cystic fibrosis (CF). Anti-Saccharomyces cerevisiae antibodies (ASCA) have been suggested as a screening tool to detect CD in CF. Recently, several new anti-glycan antibodies have been reported in CD. - MATERIALS AND METHODS: The sera of 119 CF patients of various age groups were prospectively screened for ASCA type IgG (gASCA), anti-laminaribioside carbohydrate IgG antibodies (ALCA), anti-chitobioside carbohydrate IgA antibodies (ACCA), and anti-mannobioside carbohydrate IgG antibodies (AMCA). The frequency of these anti-glycan antibodies was then compared in patients with CD, ulcerative colitis, rheumatoid arthritis and healthy volunteers. - RESULTS: A significant number of CF patients were positive for gASCA (51.3% (41.6-60.6)) and up to three other anti-glycan antibodies concurrently. Serum levels of anti-glycan antibodies in CF and CD were not related to parameters of inflammation. Despite the well-documented difference in clinical course between male and female CF patients no gender difference of anti-glycan antibodies was found. In contrast, there was a significant positive correlation between anti-glycan markers and age in CF patients. - CONCLUSIONS: Our findings demonstrate for the first time the increased frequency of a panel of anti-glycan antibodies in CF and provide a link between the presence of these serological biomarkers and patient's age. Anti-glycan antibody profiling may therefore become a valuable tool in the care of patients with CF.

Travelling with cystic fibrosis: recommendations for patients and care team members.

There are no European Guidelines on issues specifically related to travel for people with cystic fibrosis (CF). The contributors to these recommendations included 30 members of the ECORN-CF project. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Executive Agency of Health and Consumers of the European Union and the Christiane Herzog Foundation. The main goal of this paper is to provide patient-oriented advice that complements medical aspects by offering practical suggestions for all aspects involved in planning and taking a trip. The report consists of three main sections, preparation for travel, important considerations during travel and at the destination, and issues specific to immunocompromised travellers. People with CF should be encouraged to consult with their CF centre prior to travel to another country. The CF centre can advise on the necessary preparation for travel, the need for vaccinations, essential medications that should be brought on the trip and also provide information relating to CF care in the region and plan of action in case of an emergency.

Real-time tissue elastography in the diagnosis of autoimmune pancreatitis.

Endoscopic ultrasound (EUS) elastography distinguishes tissues on the basis of their specific consistency. The preoperative diagnosis of autoimmune pancreatitis (AIP) is of the utmost importance in order to avoid surgery. The aim of this prospective evaluation of five patients was to investigate the role of this new technique in the characterization of mass lesions caused by AIP, with histology as the gold standard. All five patients with AIP presented with a characteristic stiff elastographic pattern not only of the mass lesion but also of the surrounding pancreatic parenchyma, which was not found in 17 patients with ductal adenocarcinoma and 10 healthy subjects. EUS elastography of the pancreas shows a typical and unique finding with homogenous stiffness of the whole organ, and this distinguishes AIP from the circumscribed mass lesion in ductal adenocarcinoma.

Statistical limitations of percent ideal body weight as measure for nutritional failure in patients with cystic fibrosis.

BACKGROUND: For the past decade, percentage of ideal body weight (%IBW) was recommended by European and US nutrition consensus reports as preferred clinical measure of nutritional status in children with cystic fibrosis (CF). We and others have demonstrated that the %IBW method underestimates the prevalence of nutritional failure in CF, but the underlying mechanism for this methodological flaw remains incompletely defined. DESIGN: We performed model calculations from cross sectional growth data of healthy and CF-children to assess the methodological limitations of %IBW calculation. RESULTS: Here we demonstrate that an intrinsic limitation of %IBW method is that it largely ignores the statistical principle of regression to the mean. The key assumption of %IBW is that ideal weight-for-age is on exactly the same percentile ranking as height-for-age. We show that this assumption is only valid if the individual's height is close to the reference median. When the stature deviates from the median of the reference population, however, the increments of height-for-age and weight-for-age percentiles are not the same. In consequence, %IBW method systematically underestimates the ideal weight for smaller-than-average individuals, like CF-patients, which results in significant underestimation of the prevalence of malnutrition in this group of patients. CONCLUSION: There is increasing scientific evidence that calculation of %IBW as a measure of nutritional status in children with CF is flawed and should be discontinued. It is expected that future guidelines will recommend the use of alternative measures of weight-for-height proportion, e.g. BMI percentiles, to assess underweight and malnutrition in patients with CF.

Indications and limitations of endoscopic ultrasound elastography for evaluation of focal pancreatic lesions.

BACKGROUND AND STUDY AIM: Endoscopic-ultrasound-guided elastography (EUS-elastography) is a recently introduced imaging procedure that distinguishes tissues on the basis of their specific consistency. The aim of this prospective study was to investigate the role of this new technique in the characterization and differentiation of focal pancreatic lesions. PATIENTS AND METHODS: This prospective study enrolled 70 patients with unclassified solid lesions of the pancreas and 10 controls with a healthy pancreas. In all patients elastography recordings were compared with cytology/histology findings as the gold standard. RESULTS: Adequate EUS-elastography of the pancreas was performed in all healthy controls but in only 56 % of patients with solid pancreatic lesions. The main limitation of elastographic image acquisition was incomplete delineation of the border of lesions greater than 35 mm in diameter (39 %) or of lesions at some distance from the transducer (10 %). Elastographic recordings were also hampered by the fact that the surrounding tissue, which is used as an internal reference standard for strain calculation, was insufficiently displayed in the case of larger lesions. The reduced ratio of target to surrounding tissue resulted in the formation of color artifacts and in impaired reproducibility. In contrast, the majority of lesions smaller than 35 mm in diameter were adequately and reproducibly evaluated by EUS-elastography (91 %). The clinical use for differential diagnosis, however, seems limited, since strain images from all kinds of pancreatic masses were found to be harder than the surrounding tissues, irrespective of the underlying nature of the lesion (i. e., malignant vs. benign). EUS-elastography predicted the nature of pancreatic lesions with poor diagnostic sensitivity (41 %), specificity (53 %), and accuracy (45 %). CONCLUSION: EUS-elastography of the pancreas has the potential to obtain some complementary information that would improve tissue characterization. Its clinical utility, however, remains questionable, and it seems unlikely that the information provided will obviate the necessity of obtaining tissue samples for confirmation of a final pathologic diagnosis.

Oxygen generation by combined electrolysis and fuel-cell technology: clinical use in COPD patients requiring long time oxygen therapy.

BACKGROUND: Oxy-Gen lite, a recently developed combined electrolysis and fuel cell technology, de-novo generates oxygen with high purity for medical use from distilled water and room air. However, its use in patients with chronic respiratory failure has never been evaluated. OBJECTIVES: To test the clinical applicability and safety of Oxy-Gen lite technology, we enrolled 32 COPD patients with chronic hypoxemia and long-term oxygen therapy (LTOT) in a controlled, randomized, multicenter clinical trial. MATERIALS AND METHODS: Standard continuous oxygen therapy with a maximal flow rate of 2 L/min was tested against pulsatile oxygen delivery by Oxy-Gen lite. Oxygen saturation at seated-rest was recorded over 30 min and used as a primary read-out parameter. Oxygen saturation was also recorded during mild physical strain (speaking out loud) or overnight's sleep. RESULTS: Both methods of oxygen supply established oxygen saturations within the normal range (i.e., upper plateau of the sigmoid oxyhaemoglobin dissociation curve) compared to breathing room air (p<0.0001). Mean oxygen saturation under standard continuous oxygen flow or Oxy-Gen lite technology during rest, physical strain or sleep proved statistically equivalent (95%CI<2.5% of reference saturation). CONCLUSION: The use of Oxy-Gen lite in COPD patients with hypoxemia and LTOT

Evaluation of hepatic steatosis by ultrasound in patients with chronic hepatitis C virus infection.

OBJECTIVE: To compare two alternative ultrasound parameters, hepatic vein flow (HVF) pattern and presence of focal hypoechoic areas (FHA) within the liver hilus, as non-invasive predictors of liver steatosis in patients with chronic hepatitis C virus (HCV) infection. DESIGN: In 122 consecutive patients with chronic HCV infection, the HVF pattern and presence of FHA within the liver hilus were assessed by Duplex-Doppler and B-mode sonography. All patients underwent liver biopsy and the sonographic results were compared with a histological score of steatosis used as the gold standard for this purpose. Association of fatty infiltrations with clinical and sonographic features were evaluated by a stepwise logistic regression analysis. RESULTS: Reduced HVF and FHA, but not standard clinical and laboratory parameters, strongly correlated with steatosis on histology (P<0.001). Both sonographic parameters made excellent predictions for the subgroup of patients with severe steatosis, particularly when both tests were combined [sensitivity (SE) 95%, specificity (SP) 96%, positive predictive value (pPV) 93%, negative predictive value (nPV) 97%, and accuracy 96%]. However, the sensitivity and accuracy of HVF pattern analysis were markedly reduced when all degrees of steatosis were defined as positive (SE 71%, SP 76%, pPV 81%, nPV 64%, and accuracy 73%). In contrast, the dichotomous parameter FHA remained a powerful indicator even under the latter conditions (SE 74%, SP 100%, pPV 100%, nPV 72%, and accuracy 84%). The combination of both sonographic tests resulted in improved sensitivity (82%), but significant loss of specificity (76%) and accuracy (80%) for prediction of liver steatosis. CONCLUSION: Sonographic evaluation of reduced HVF and FHA within the liver hilum is easy to perform, non-invasive, and, when present, gives a high degree of confidence in the diagnosis of liver steatosis. However, the lack of sonographic evidence of steatosis cannot definitively exclude the presence of mild steatosis, as shown on biopsy.

Evaluation of body mass index percentiles for assessment of malnutrition in children with cystic fibrosis.

OBJECTIVE: To compare the performance of recently released body mass index percentiles (BMIp) with standard anthropometric indexes, including height-for-age percentile (HAP), weight-for-age percentile (WAP) and percent ideal body weight (%IBW), as measures for nutritional failure in children with cystic fibrosis (CF). DESIGN: Cross-sectional analysis of growth and lung function data from 4577 children with CF reported to the German CF quality assurance (CFQA) project from 1995 to 2004. RESULTS: Frequency distribution of HAP (mean+/-s.d.: male 30.0+/-27.5; female 31.3+/-27.4) and WAP (male 28.9+/-27.0; female 29.6+/-26.7) were skewed, with significant numbers of patients below the fifth percentiles of a healthy reference population. However, because deficits occurred in both measures simultaneously, mean %IBW (male 97.0+/-12.1; female 98.1+/-12.3) assumed subjects weight close to the nominal weight-for-height at all ages. In contrast, mean BMIp was markedly reduced (male 35.7+/-27.9; female 35.6+/-27.2) and steadily declined with age. Ideal weight-for-age was significantly lower when predicted by %IBW compared with BMIp method, particularly in subjects with shorter-than-average stature. Consequently, less CF children were identified with nutritional failure according to %IBW method (male 20.5%; female 22.7%) compared with BMIp method (male 30.4%; female 28.7%). The clinical relevance of these findings was confirmed by stronger correlation of BMIp with impaired %forced expiratory volume/s, a marker for disease progression in CF. CONCLUSION: BMIp predicts nutritional failure more sensitively and accurately than conventional anthropometric indexes, at least in children with CF. Screening of CF patients by BMIp could provide an early warning sign and allow for timely therapeutic intervention.

[New concepts of pathophysiology and therapy in cystic fibrosis]. / Neue Konzepte zur Pathophysiologie und Therapie der Mukoviszidose.

Today, the majority of cystic fibrosis (CF) patients treated in Germany have reached adulthood. However, with increasing age the morbidity and frequency of severe pulmonary complications continues to rise. Further optimization of conventional therapy alone will be insufficient to compensate for this development. In recent years, there has been impressive progress in our understanding of the molecular basis of the CF gene and its product, the cystic fibrosis transmembrane conductance regulator (CFTR). This knowledge can now be applied to develop new therapeutic strategies. However, important questions remain to be solved, i. e., little is known about the pathways that link the malfunctioning of the CFTR protein with the observed clinical phenotype. This review briefly touches on CF genetics as it applies to lung disease and will focus on the current hypotheses of CFTR (dys)function and its impact on pulmonary fluid homeostasis. New treatment options that target the molecular basis of the disease will be discussed.

[Sonographie von pleura und lunge]. / Ultrasonography of Pleura and Lung.

The value of ultrasound examination of the pleura and lungs remains highly underestimated to this day. While the ventilated lungs and the osseous skeleton of the thorax represent potent obstacles for ultrasound, a multitude of pathological processes of the chest wall, pleura, and lungs results in altered tissue composition, providing markedly increased access and visibility for sonographic examination. These conditions support the sonographic diagnosis of pleural and pulmonary disorders. However, the main value of pleura and lung ultrasonography is not the primary diagnosis of chest lesions but the follow up, differential diagnosis, detection of complications, such as abscesses and post embolic lung infarction, and guidance of diagnostic and therapeutic interventions in patients with pathological pleural and pulmonary findings. Punctures and drainages of fluids, e. g., haematothorax, empyema, chylothorax as well as biopsies of solid lesions can safely be performed under ultrasound-guidance. It is of special importance that pleura and lung ultrasonography, as a non-invasive method, can be repeated without discomfort or radiation exposure for the patient and is therefore valuable in the follow-up of pathological findings. Adequate interpretation of sonographic pleura and lung findings has to consider the patient's history, physical examination, chest X-ray and other results obtained by complementary imaging technologies (e. g. thoracic computed tomography).

The value of routinely performed ultrasonography in patients with Crohn disease.

BACKGROUND: In active Crohn disease (CD), abdominal ultrasound can demonstrate morphological changes in the bowel wall. By contrast, the role of ultrasonography in periods with no disease activity has never been evaluated. In this prospective study we investigated the outcome of routinely performed abdominal ultrasonography in CD patients irrespective of symptoms and disease activity. METHODS: 255 consecutive patients with chronic CD (117 M, 138 F, mean age (+/-s) 38 +/- 14) were evaluated by high-resolution ultrasonography of the bowel wall and abdomen. The findings were graded with respect to further diagnostic and/or therapeutic implications. In addition, the CD activity index (CDAI) was determined. In patients with pathological sonographic findings, complementary procedures (e.g. endoscopy, computed tomography, biopsy or operation) were performed to validate the suspected diagnosis. RESULTS: In 46/255 (18%) patients with CD, the diagnosis of a transmural inflammatory reaction (TMR) with or without fistula was made by ultrasonography. In respect of CDAI, 29/46 (63%) of these patients were graded as active disease (CDAI > 150) and 17/46 (37%) as inactive disease (CDAI < or = 150). Of the 17 patients with a TMR and CDAI < or = 150, 4 patients revealed interenteric fistula, 7 patients mesenteric or perirectal fistula, whereas 6 patients presented with a transmural mesenteric inflammatory reaction without fistula. All fistulae were confirmed by radiography. Ultrasonography of the remaining abdominal organs revealed pathological findings with further diagnostic implications in 25/255 (10%) patients and with therapeutic implications in 9/255 (4%) patients. CONCLUSION: Routinely performed ultrasonography of the abdomen reveals pathological findings with therapeutic implications not only in symptomatic but also in asymptomatic patients with CD. It can therefore be recommended as a screening tool for this group of patients.

[Crack-syndrome: the pulmonary complications of inhaled cocaine. A review a propos a case report]. / Crack-Syndrom: Pulmonale Komplikationen nach Kokaininhalation--Kasuistik und Darstellung des Krankheitsbildes.

A 45-year-old patient developed shortness of breath, intensive cough, hemoptysis, chest pain and acute bilateral pulmonary infiltrates following the inhalation of crack-cocaine. The bronchoalveolar lavage and transbronchial biopsy revealed infiltrations of polymorphonuclear neutrophils and the formation of foreign body granulomas. The diagnosis of a crack-syndrome was made and the patient rapidly improved under temporary discontinuation of cocaine inhalation and symptomatic therapy. Crack-cocaine is the free-base of cocaine-hydrochloride and its chemical properties allows it to be inhaled tobacco-like. Therefore the lungs become the principal organs exposed and affected. In addition to our findings, diffuse damage of the alveolar wall and capillary injury due to vasoconstriction and toxic action were reported, in some cases rapidly progressing into pulmonary oedema and ARDS. As the consumption of crack cocaine in Germany has markedly increased over the past decade, a higher prevalence of the reported syndrome has to be assumed.