Ultrasound of the pleurae and lungs.

The value of ultrasound techniques in examination of the pleurae and lungs has been underestimated over recent decades. One explanation for this is the assumption that the ventilated lungs and the bones of the rib cage constitute impermeable obstacles to ultrasound. However, a variety of pathologies of the chest wall, pleurae and lungs result in altered tissue composition, providing substantially increased access and visibility for ultrasound examination. It is a great benefit that the pleurae and lungs can be non-invasively imaged repeatedly without discomfort or radiation exposure for the patient. Ultrasound is thus particularly valuable in follow-up of disease, differential diagnosis and detection of complications. Diagnostic and therapeutic interventions in patients with pathologic pleural and pulmonary findings can tolerably be performed under real-time ultrasound guidance. In this article, an updated overview is given presenting not only the benefits and indications, but also the limitations of pleural and pulmonary ultrasound.

Ultrasound evaluation of mediastinal lymphadenopathy in patients with sarcoidosis.

AIM: Mediastinal lymphadenopathy is a typical feature of pulmonary sarcoidosis and an important parameter for diagnosis and follow-up. The present feasibility study is the first to elucidate the role of transthoracic mediastinal ultrasonography (US) for evaluation and staging of lymphadenopathy in patients with sarcoidosis. MATERIAL AND METHOD: Fifty patients with sarcoidosis were subjected to high-definition mediastinal US. The sonographic lymph node status was compared with the radiologic staging - the prevailing gold standard. RESULTS: Mediastinal regions and landmarks could reliably be assessed by ultrasound in 45/50 (90%) of sarcoidosis patients. Lymphadenopathy was sonographically documented in 29/50 (58%) of the patients (sensitivity 89%, specificity 76%, PPV 86%, NPV 81%, accuracy 84%). There was a marked concordance between US confirmation of lymphadenopathy and radiologic staging (k=0.67, p<0.001). CONCLUSIONS: Transthoracic US qualifies for the demonstration of the mediastinal regions and lymphadenopathy in patients with sarcoidosis. The procedure is facilitated by frequent and distinct mediastinal lymph node enlargement due to sarcoidosis. Prospective studies are required to find out whether mediastinal US adds value to conventional radiologic staging and provides a clinically advantage, particularly in the follow-up of patients with sarcoidosis.

Bullous emphysema - Not always nicotine-related!: Unusual distribution of emphysema in a patient with a rare hobby.

In a patient admitted for further investigation of haemoptysis and dyspnoea and known emphysema of the lung, a remarkable distribution of emphysematous bullae could be detected on CT-imaging. Further history, besides smoking, revealed apnoea diving-activity during younger adult age. The distinct appearance of partially septated pleura-based bullae lead to the suspicion of a positive-pressure barotrauma of the lungs in the past, now complicated by infection and bleeding. This case highlights the importance of thorough questioning of the patient and underlines the consideration of differential diagnoses of emphysema.

Assessment of a new e-learning system on thorax, trachea, and lung ultrasound.

Background. Lung ultrasound has become an emerging tool in acute and critical care medicine. Combined theoretical and hands-on training has been required to teach ultrasound diagnostics. Current computer technology allows for display, explanation, and animation of information in a remote-learning environment. Objective. Development and assessment of an e-learning program for lung ultrasound. Methods. An interactive online tutorial was created. A prospective learning success study was conducted with medical students using a multiple-choice test (Trial A). This e-learning program was used as preparation for a certified course followed by an evaluation of trained doctors (Trial B) by linear analogue scales. Pretests were compared with postcourse tests and sustainability tests as well as a posttest of a one-day custom classroom training. Results. In Trial A, during the learning success study (n = 29), the increase of correct answers was 11.7 to 17/20 in the post-test and to 16.6/20 in the sustainability test (relative change 45.1%, P < 0.0001). E-learning almost equalled scores of classroom-based training regarding gain and retention of factual knowledge. In Trial B, nineteen participating doctors found a 79.5% increase of knowledge (median, 95% CI: 69%; 88%). Conclusion. The basics of lung ultrasound can be taught in a highly effective manner using e-learning.

Myeloperoxidase-dependent inactivation of surfactant protein D in vitro and in vivo.

Surfactant protein D (SP-D) plays diverse and important roles in innate immunity and pulmonary homeostasis. Neutrophils and myeloperoxidase (MPO) colocalized with SP-D in a murine bacterial pneumonia model of acute inflammation, suggesting that MPO-derived reactive species might alter the function of SP-D. Exposure of SP-D to the complete MPO-H(2)O(2)-halide system caused loss of SP-D-dependent aggregating activity. Hypochlorous acid (HOCl), the major oxidant generated by MPO, caused a similar loss of aggregating activity, which was accompanied by the generation of abnormal disulfide-cross-linked oligomers. A full-length SP-D mutant lacking N-terminal cysteine residues and truncation mutants lacking the N-terminal domains were resistant to the oxidant-induced alterations in disulfide bonding. Mass spectroscopy of HOCl-treated human SP-D demonstrated several modifications, but none involved key ligand binding residues. There was detectable oxidation of cysteine 15, but no HOCl-induced cysteine modifications were observed in the C-terminal lectin domain. Together, the findings localize abnormal disulfide cross-links to the N-terminal domain. MPO-deficient mice showed decreased cross-linking of SP-D and increased SP-D-dependent aggregating activity in the pneumonia model. Thus, MPO-derived oxidants can lead to modifications of SP-D structure with associated alterations in its characteristic aggregating activity.

Increased frequency of regulatory T cells and selection of highly potent CD62L+ cells during treatment of human lung transplant recipients with rapamycin.

The currently available immunosuppressive agents applied in human transplantation medicine are highly potent in the protection from acute allograft rejection. However, long-term allograft survival is still poor as these drugs fail to sufficiently prevent chronic allograft rejection. Naturally occurring regulatory T cells have been postulated as the key players to establish long-lasting transplantation tolerance. Thus, the development of immunosuppressive regimens which shift the pathological balance of cytopathic versus regulatory T cells of human allograft recipients towards a protective T-cell composition is a promising approach to overcome limitations of current transplantation medicine. Thirty-three patients that received rapamycin (RPM) or calcineurin inhibitor treatment following lung transplantation were included and their T-cell compartments analysed. Twelve healthy volunteers without history of lung disease served as controls. In this article, we show that treatment of human lung transplant recipients with RPM is associated with an increased frequency of regulatory T cells, as compared with treatment with calcineurin inhibitors or to healthy controls. Moreover, regulatory T cells during treatment with RPM were CD62Lhigh, a phenotype that displayed an enhanced immunosuppressive capacity ex vivo. Our data support the use of RPM in human lung transplant recipients and undertaking of further prospective studies evaluating its impact on allograft and patient survival.

Neutrophil elastase mediates innate host protection against Pseudomonas aeruginosa.

According to the widely accepted view, neutrophil elastase (NE), a neutrophil-specific serine protease, is a major contributor to Pseudomonas aeruginosa infection-associated host tissue inflammation and damage, which in severe cases can lead to death. Herein, we provide for the first time compelling evidence that the host rather employs NE to protect itself against P. aeruginosa infection. Using a clinically relevant model of pneumonia, targeted deficiency in NE increased the susceptibility of mice to P. aeruginosa. We found that NE was required for maximal intracellular killing of P. aeruginosa by neutrophils. In investigating the mechanism of NE-mediated killing of P. aeruginosa, we found that NE degraded the major outer membrane protein F, a protein with important functions, including porin activity, maintenance of structural integrity, and sensing of host immune system activation. Consistent with this, the use of an isogenic mutant deficient in outer membrane protein F negated the role of NE in host defense against P. aeruginosa infection.

Myeloperoxidase plays critical roles in killing Klebsiella pneumoniae and inactivating neutrophil elastase: effects on host defense.

Activated neutrophils use myeloperoxidase (MPO) to generate an array of potent toxic oxidants. In the current studies we used genetically altered mice deficient in MPO to investigate the role of the enzyme in host defense against the Gram-negative bacterium Klebsiella pneumoniae, an important human pathogen. For comparison, we used mice deficient in the antimicrobial molecule, neutrophil elastase (NE). When challenged i.p., mice deficient in either MPO or NE were markedly more susceptible to bacterial infection and death. In vitro studies suggested that MPO impairs the morphology of bacteria in a distinctive way. Of importance, our in vitro studies found that MPO mediated oxidative inactivation of NE, an enzyme that has been widely implicated in the pathogenesis of various tissue-destructive diseases. This pathway of oxidative inactivation may be physiologically relevant, because activated neutrophils isolated from MPO-deficient mice exhibited increased elastase activity. Our observations provide strong evidence that MPO, like NE, is a key player in the killing of K. pneumoniae bacteria. They also suggest that MPO may modulate NE to protect the host from the tissue-degrading activity of this proteinase.

Neutrophil serine proteinases inactivate surfactant protein D by cleaving within a conserved subregion of the carbohydrate recognition domain.

Surfactant protein D (SP-D) plays important roles in innate immunity including the defense against bacteria, fungi, and respiratory viruses. Because SP-D specifically interacts with neutrophils that infiltrate the lung in response to acute inflammation and infection, we examined the hypothesis that the neutrophil-derived serine proteinases (NSPs): neutrophil elastase, proteinase-3, and cathepsin G degrade SP-D. All three human NSPs specifically cleaved recombinant rat and natural human SP-D dodecamers in a time- and dose-dependent manner, which was reciprocally dependent on calcium concentration. The NSPs generated similar, relatively stable, disulfide cross-linked immunoreactive fragments of approximately 35 kDa (reduced), and sequencing of a major catheptic fragment definitively localized the major sites of cleavage to a highly conserved subregion of the carbohydrate recognition domain. Cleavage markedly reduced the ability of SP-D to promote bacterial aggregation and to bind to yeast mannan in vitro. Incubation of SP-D with isolated murine neutrophils led to the generation of similar fragments, and cleavage was inhibited with synthetic and natural serine proteinase inhibitors. In addition, neutrophils genetically deficient in neutrophil elastase and/or cathepsin G were impaired in their ability to degrade SP-D. Using a mouse model of acute bacterial pneumonia, we observed the accumulation of SP-D at sites of neutrophil infiltration coinciding with the appearance of approximately 35-kDa SP-D fragments in bronchoalveolar lavage fluids. Together, our data suggest that neutrophil-derived serine proteinases cleave SP-D at sites of inflammation with potential deleterious effects on its biological functions.

Sonographic detection of perihepatic lymphadenopathy is an indicator for primary sclerosing cholangitis in patients with inflammatory bowel disease.

AIM: Primary sclerosing cholangitis (PSC) is a frequent complication in patients with inflammatory bowel disease (IBD). While hyperplasia of the perihepatic lymph nodes has been described in patients with PSC, its prevalence and cause in IBD patients remains obscure. In the present study we address the question of whether ultrasound (US) examination is useful to detect perihepatic lymphadenopathy and improve the diagnostic accuracy for PSC in patients with underlying IBD. METHODS: A total of 310 consecutive IBD patients were prospectively evaluated by US for enlarged perihepatic lymph nodes, as well as serologic testing for cholestasis-indicating enzymes. In patients with positive test results, viral or autoimmune liver disorders were excluded by serum testing. Next, the presence of PSC was confirmed/excluded by endoscopic retrograde cholangiography (ERC). RESULTS: Perihepatic lymphadenopathy was detected by US in 27 of 310 (9%) patients. In 9 (33%) of those, serologic testing identified an underlying autoimmune or viral hepatitis. In the remaining 18 patients, ERC confirmed PSC in 17 (94%) and excluded it in 1. Elevated cholestasis parameters were found in 43 of 310 (14%) patients and 5 (12%) of those were diagnosed with autoimmune or viral hepatitis. In the remaining 38 patients, ERC confirmed PSC in 15 (39%) and excluded it in 23 (61%). Therefore, when autoimmune or viral hepatitis was excluded, enlarged lymph nodes in US predicted PSC more accurately than conventional serum parameters alone (PPV 94 and 39%, respectively [ P<0.001]), and the sensitivity ratio increased by a factor of 1.13 in favor of the US examination. CONCLUSION: In patients with IBD, detection of enlarged perihepatic lymph nodes is a highly predictive indicator for the presence of PSC. Alternative causes of perihepatic lymphadenopathy have to be excluded.

Deficiency in neutrophil elastase does not impair neutrophil recruitment to inflamed sites.

To reach the sites of inflammation, neutrophils traverse the endothelium, its underlying basement membrane, and other barriers depending on the localization of the insulting agent. Whether neutrophil elastase (NE) plays a role in neutrophil recruitment to inflamed sites is still debatable. By exploiting mice deficient in NE (NE(-/-)), we sought to address this dilemma. We recruited neutrophils to the lungs or the peritoneum of wild-type (WT) or NE(-/-) mice by intranasal or intraperitoneal challenge with Pseudomonas aeruginosa or its lipopolysaccharide. At designated times post-inoculation (0, 4, 24, and 48 h), groups of mice were killed to assess changes in leukocyte counts and inflammatory responses. NE(-/-) and WT mice had normal circulating leukocyte numbers including neutrophils and changes in the hemograms in the setting of acute inflammation were indistinguishable. Analyses of lung tissues or fluids from the lungs and peritoneum found that regardless of the inflammatory model, the leukocyte counts including neutrophils and the inflammatory response were similar in NE(-/-) and WT mice at all time points. In vitro, neutrophils isolated from the lungs or the peritoneum of NE(-/-) and WT mice had comparable chemotactic and respiratory-burst functions and migrated normally through Matrigel in response to various stimuli. Interestingly, preincubation of human peripheral blood neutrophils with NE physiologic inhibitors did not alter the migration of the cells through Matrigel. In sum, our findings present the first in vivo description that the absence of NE does not impair neutrophil recruitment to inflamed sites and that NE is not required for basement membrane transmigration of neutrophils.

[Mediastinal ultrasound: technique and possible applications]. / Mediastinalsonographie: Technik und Anwendungsmöglichkeiten.

When a mediastinal disease is suspected, the conventional chest X-ray remains the diagnostic procedure of first choice. However, the gold standard for evaluation of the mediastinum is represented by thoracic computed tomography, which demonstrates all important structures of this region and supplies information about pathologic changes of the lung hilus and parenchyma. Until today, with the exception of echocardiography, noninvasive sonographic examination of the mediastinum is not routinely performed. The potential of this procedure, which is supported by the good accessibility to the region and its predominantly solid structure, appears not yet adequately used. To evaluate and compare the sonographic findings, it seems essential to establish a standardized examination procedure as well as a clear definition of anatomic regions. Since lymphadenopathy represents the most frequent pathologic finding in the mediastinum, the definition of the mediastinal regions is made with respect to the lymphatic pathways. Clinically relevant mediastinal lesions are predominantly located in the aortopulmonary window or the paratracheal region, which both permit facile access for sonographic examination. A transcutaneous diagnostic or therapeutic puncture of mediastinal lesions can safely be performed under sonographic guidance.

Sonographic findings of the hepatobiliary-pancreatic system in adult patients with cystic fibrosis.

OBJECTIVE: Sonography of the liver, biliary system, and pancreas in adult patients with cystic fibrosis is by far less systematically documented than in pediatric patients with cystic fibrosis. In this prospective study, duplex sonographic findings of the liver, biliary system, and pancreas in adult patients with cystic fibrosis were compared with those of healthy control subjects. METHODS: Seventy-two consecutive patients with cystic fibrosis and 60 healthy control subjects were examined by high-resolution sonography. The incidence of perihepatic lymphadenopathy, the hepatic echo pattern, the detection rate of liver tumors, the flow patterns in the hepatic and portal veins, and pathologic gallbladder and pancreas findings were recorded. Additionally, cholestasis-indicating enzyme levels (gamma-glutamyl transpeptidase and alkaline phosphatase), liver function test results (alanine aminotransferase and aspartate aminotransferase levels), and amylase and lipase levels were recorded as well. RESULTS: Patients with cystic fibrosis, when compared with healthy subjects on sonographic examination, had a higher incidence of microgallbladder (25% versus 0%) and cystic lesions of the pancreas (18% versus 0%). The number of abnormal echo patterns of the liver was increased (46% versus 15%), with a higher incidence of a nontriphasic flow pattern in the right hepatic vein. The differences proved to be statistically significant (P < .05). CONCLUSIONS: Typical sonographic findings in adult patients with cystic fibrosis are a microgallbladder and small cystic lesions of the pancreas. Pathologic findings of the liver can be shown by B-mode and duplex sonography, but the resulting patterns are less characteristic.