Claus Peter Heußel

Automatic airway analysis on multidetector computed tomography in cystic fibrosis: correlation with pulmonary function testing.

Purpose: To evaluate the fully automatic quantification of airway dimensions on chest multidetector computed tomography (MDCT) performed in cystic fibrosis (CF) patients. Airflow indices including predicted forced expiratory volume in 1 second (FEV1%) were used to study the impact on regional lung function. Materials and Methods: MDCT data of patients with CF (14 children and 23 adults) and of control patients (11 children and 22 adults) were used to compute total diameter (TD), lumen area (LA), and wall thickness (WT) using dedicated software. Pulmonary function testing including FEV1% was performed in parallel and correlated with MDCT parameters in a generation-based analysis. Results: TD was largely increased in CF patients (third-generation to fourth-generation airways in children, first to ninth in adults; P<0.05). LA remained unchanged, but WT was also larger in CF compared with controls (third generation to sixth generation in children, first to eleventh in adults; P<0.05). In adult CF patients significant negative correlations for TD, LA, and WT with FEV1% were found for intermediate airways (fifth to seventh generation; r=−0.7 to −0.9) but not in pediatric CF patients and controls. Conclusions: Automatic airway analysis succeeded in quantifying specific pathologies such as airway dilatation and wall thickening in CF patients at different ages. Moreover, our results indicate a shift in main airflow resistance to intermediate airways in cases of chronic CF. The objective computational parameters TD, LA, and WT should be considered for assessment and follow-up of CF airway disease.

Pulmonary emphysema in cystic fibrosis detected by densitometry on chest multidetector computed tomography.

Background Histopathological studies on lung specimens from patients with cystic fibrosis (CF) and recent results from a mouse model indicate that emphysema may contribute to CF lung disease. However, little is known about the relevance of emphysema in patients with CF. In the present study, we used computationally generated density masks based on multidetector computed tomography (MDCT) of the chest for non-invasive characterization and quantification of emphysema in CF. Methods Volumetric MDCT scans were acquired in parallel to pulmonary function testing in 41 patients with CF (median age 20.1 years; range 7-66 years) and 21 non-CF controls (median age 30.4 years; range 4-68 years), and subjected to dedicated software. The lung was segmented, low attenuation volumes below a threshold of -950 Hounsfield units were assigned to emphysema volume (EV), and the emphysema index was computed (EI). Results were correlated with forced expiratory volume in 1 s percent predicted (FEV1%), residual volume (RV), and RV/total lung capacity (RV/TLC). Results We show that EV was increased in CF (457±530 ml) compared to non-CF controls (78±90 ml) (P<0.01). EI was also increased in CF (7.7±7.5%) compared to the control group (1.2±1.4%) (P<0.05). EI correlated inversely with FEV1% (rs=-0.66), and directly with RV (rs=0.69) and RV/TLC (rs=0.47) in patients with CF (P<0.007), but not in non-CF controls. Emphysema in CF was detected from early adolescence (~13 years) and increased with age (rs=0.67, P<0.001). Conclusions Our results indicate that early onset emphysema detected by densitometry on chest MDCT is a characteristic pathology that contributes to airflow limitation and may serve as a novel endpoint for monitoring lung disease in CF.

Identification of invasive fungal diseases in immunocompromised patients by combining an Aspergillus specific PCR with a multifungal DNA-microarray from primary clinical samples

The increasing incidence of invasive fungal diseases (IFD), most of all invasive aspergillosis (IA) in immunocompromised patients emphasises the need to improve the diagnostic tools for detection of fungal pathogens. We investigated the diagnostic performance of a multifungal DNA‐microarray detecting 15 different fungi [Aspergillus, Candida, Fusarium, Mucor, Rhizopus, Scedosporium and Trichosporon species (spp.)] in addition to an Aspergillus specific polymerase chain reaction (PCR) assay. Biopsies, bronchoalveolar lavage and peripheral blood samples of 133 immunocompromised patients (pts) were investigated by a multifungal DNA‐microarray as well as a nested Aspergillus specific PCR assay. Patients had proven (n = 18), probable (n = 29), possible (n = 48) and no IFD (n = 38) and were mostly under antifungal therapy at the time of sampling. The results were compared to culture, histopathology, imaging and serology, respectively. For the non‐Aspergillus IFD the microarray analysis yielded in all samples a sensitivity of 64% and a specificity of 80%. Best results for the detection of all IFD were achieved by combining DNA‐microarray and Aspergillus specific PCR in biopsy samples (sensitivity 79%; specificity 71%). The molecular assays in combination identify genomic DNA of fungal pathogens and may improve identification of causative pathogens of IFD and help overcoming the diagnostic uncertainty of culture and/or histopathology findings, even during antifungal therapy.

Clinical outcome of hypofractionated breath-hold image-guided SABR of primary lung tumors and lung metastases.

BackgroundStereotactic Ablative RadioTherapy (SABR) of lung tumors/metastases has been shown to be an effective treatment modality with low toxicity. Outcome and toxicity were retrospectively evaluated in a unique single-institution cohort treated with intensity-modulated image-guided breath-hold SABR (igSABR) without external immobilization. The dose–response relationship is analyzed based on Biologically Equivalent Dose (BED).Patients and methods50 lesions in 43 patients with primary NSCLC (n = 27) or lung-metastases of various primaries (n = 16) were consecutively treated with igSABR with Active-Breathing-Coordinator (ABC®) and repeat-breath-hold cone-beam-CT. After an initial dose-finding/-escalation period, 5x12 Gy for peripheral lesions and single doses of 5 Gy to varying dose levels for central lesions were applied. Overall-survival (OS), progression-free-survival (PFS), progression pattern, local control (LC) and toxicity were analyzed.ResultsThe median BED2 was 83 Gy. 12 lesions were treated with a BED2 of <80 Gy, and 38 lesions with a BED2 of >80 Gy. Median follow-up was 15 months. Actuarial 1- and 2-year OS were 67% and 43%; respectively. Cause of death was non-disease-related in 27%. Actuarial 1- and 2-year PFS was 42% and 28%. Progression site was predominantly distant. Actuarial 1- and 2 year LC was 90% and 85%. LC showed a trend for a correlation to BED2 (p = 0.1167). Pneumonitis requiring conservative treatment occurred in 23%.ConclusionIntensity-modulated breath-hold igSABR results in high LC-rates and low toxicity in this unfavorable patient cohort with inoperable lung tumors or metastases. A BED2 of <80 Gy was associated with reduced local control.

Radiological Diagnosis in Lung Disease: Factoring Treatment Options Into the Choice of Diagnostic Modality

BACKGROUND Chest X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) each have characteristic advantages and disadvantages that need to be considered in clinical decision-making. This point is discussed in reference to the main types of lung disease that are encountered in practice. METHOD A selective literature search was performed in the PubMed and Google Scholar databases. Existing clinical guidelines on the main types of lung disease and studies concerning radiological diagnosis were also con - sidered in this review. RESULTS There have been no more than a few large-scale, controlled comparative trials of different radiological techniques. Chest X-ray provides general orientation as an initial diagnostic study and is especially useful in the diagnosis of pneumonia, cancer, and chronic obstructive pulmonary disease (COPD). Multi-detector CT affords nearly isotropic spatial resolution at a radiation dose of only 0.2-5 mSv, much lower than before. Its main indications, according to current guidelines, are tumors, acute pulmonary embolism, pulmonary hypertension, pulmonary fibrosis, advanced COPD, and pneumonia in a high-risk patient. MRI is used in the diagnosis of cystic fibrosis, pulmonary embolism, pulmonary hypertension, and bronchial carcinoma. The positive predictive value (PPV) of a chest X-ray in outpatients with pneumonia is only 27% (gold standard, CT); in contrast, an initial, non-randomized trial of MRI in nosocomial pneumonia revealed a PPV of 95%. For the staging of mediastinal lymph nodes in bronchial carcinoma, MRI has a PPV of 88% and positron emission tomography with CT (PET/CT) has a PPV of 79%, while CT alone has a PPV of 41% (gold standard, histology). CONCLUSION The choice of radiologicalal technique for the detection, staging, follow-up, and quantification of lung disease should be based on the individual clinical options, so that appropriate treatment can be provided without excessive use of diagnostic testing.

Nine-year Experience: Prophylactic Cranial Irradiation in Extensive Disease Small-cell Lung Cancer

Background In 2007, the European Organization for Research and Treatment of Cancer (EORTC) study (ClinicalTrials.gov identifier, NCT00016211) demonstrated a beneficial effect on overall survival (OS) with the use of prophylactic cranial irradiation (PCI) for extensive disease (ED) small‐cell lung cancer (SCLC). Nevertheless, debate is ongoing regarding the role of PCI, because the patients in that trial did not undergo magnetic resonance imaging (MRI) of the brain before treatment. Also, a recent Japanese randomized trial showed a detrimental effect of PCI on OS in patients with negative pretreatment brain MRI findings. Materials and Methods We examined the medical records of 136 patients with ED SCLC who had initially responded to chemotherapy and undergone PCI from 2007 to 2015. The outcomes, radiation toxicity, neurologic progression‐free survival, and OS after PCI were analyzed. Survival and correlations were calculated using log‐rank and univariate Cox proportional hazard ratio analyses. Results The median OS and the median neurologic progression‐free survival after PCI was 12 and 19 months, respectively. No significant survival difference was seen for patients who had undergone MRI before PCI compared with patients who had undergone contrast‐enhanced computed tomography (P = .20). Univariate analysis for OS did not show a statistically significant effect for known cofactors. Conclusion In the present cohort, PCI was associated with improved survival compared with the PCI arm of the EORTC trial, with a nearly doubled median OS period. Also, the median OS was prolonged by 2 months compared with the irradiation arm of the Japanese trial. Micro‐Abstract In 2007, a European Organization for Research and Treatment of Cancer (EORTC) study demonstrated a beneficial effect on overall survival (OS) with the use of prophylactic cranial irradiation (PCI) in extensive disease small‐cell lung cancer. Nevertheless, debate is ongoing regarding the role of PCI, because the patients in that trial did not undergo imaging of the brain before treatment. Also, a recent Japanese randomized trial showed a detrimental effect of PCI on OS in patients with negative pretreatment brain magnetic resonance imaging findings. Of our patients, 87% underwent brain imaging before PCI. In the present retrospective analysis, we found that PCI leads to a nearly doubled median OS compared with the irradiation arm of the EORTC trial, with a 2‐month prolonged median OS compared with the irradiation arm of the Japanese trial.

Pleuraherd auf Wanderschaft

ZusammenfassungEin 74-jähriger Patient mit nichtkleinzelligem Bronchialkarzinom wurde aufgrund funktioneller Inoperabilität mittels Radiofrequenzablation behandelt. Die native Thorax-CT zeigte neben dem Tumor eine Verkalkung im Pleuraspalt in wechselnder Lokalisation an zwei aufeinander folgenden Tagen. Dieser extrem seltene Befund einer Thorakolithiasis stellt in der Regel einen Zufallsbefund dar. Die pleuralen Verkalkungen sind normalerweise asymptomatisch und erfordern keine Therapie. Thorakolithiasis ist eine Differenzialdiagnose des peripheren Lungenrundherdes.AbstractA 74-year-old man with bronchial carcinoma underwent radiofrequency ablation (RFA) due to poor pulmonary function. Therefore non-enhanced computed tomography (CT) of the chest was performed on two subsequent days. Besides the tumor, the CT scans showed a moving calcification in the pleural cavity. This extremely rare condition called thoracolithiasis is usually an incidental finding. Mostly it is asymptomatic and does not require any treatment. It should be considered as a differential diagnosis of a peripheral pulmonary nodule.A 74-year-old man with bronchial carcinoma underwent radiofrequency ablation (RFA) due to poor pulmonary function. Therefore non-enhanced computed tomography (CT) of the chest was performed on two subsequent days. Besides the tumor, the CT scans showed a moving calcification in the pleural cavity. This extremely rare condition called thoracolithiasis is usually an incidental finding. Mostly it is asymptomatic and does not require any treatment. It should be considered as a differential diagnosis of a peripheral pulmonary nodule.

Prospective evaluation of a combination of fungal biomarkers for the diagnosis of invasive fungal disease in high-risk haematology patients

We prospectively evaluated a combination of fungal biomarkers in adult haematology patients with focus on their clinical utility at different time points during the course of infection. In total, 135 patients were monitored once to twice weekly for serum (1‐3)‐ß‐d‐glucan (BG), galactomannan (GM), bis‐methyl‐gliotoxin and urinary d‐arabinitol/l‐arabinitol ratio. In all, 13 cases with proven or probable invasive fungal disease (IFD) were identified. The sensitivity of BG and GM at the time of diagnosis (TOD) was low, but within 2 weeks from the TOD the sensitivity of BG was 92%. BG >800 pg/mL was highly specific for IFD. At a pre‐test probability of 12%, both BG and GM had negative predictive values (NPV) >0.9 but low positive predictive values (PPV). In a subgroup analysis of patients with clinically suspected IFD (pre‐test probability of 35%), the NPV was lower, but the PPV for BG was 0.86 at cut‐off 160 pg/mL. Among IFD patients, 91% had patterns of consecutively positive and increasing BG levels. Bis‐methyl‐gliotoxin was undetectable in 15 patients with proven, probable and possible IA. To conclude, BG was the superior fungal marker for IFD diagnosis. Quantification above the limit of detection and graphical evaluation of the pattern of dynamics are warranted in the interpretation of BG results.

Generation of a New Disease-specific Prognostic Score for Patients With Brain Metastases From Small-cell Lung Cancer Treated With Whole Brain Radiotherapy (BMS-Score) and Validation of Two Other Indices

&NA; The purpose of this study was to develop a prognostic score for patients with brain metastases from SCLC treated with WBRT (BMS‐score). The new BMS score was more prognostic than the RPA and ds‐GPA score. BMS score and RPA showed the most significant differences between classes. Introduction: Patients with small‐cell lung cancer (SCLC) demonstrate an exception in the treatment of brain metastases (BM), because in patients with SCLC whole brain radiotherapy (WBRT) only is the preferred treatment modality. The purpose of this study was to develop a prognostic score for patients with brain metastases from SCLC treated with WBRT. Patients and Methods: The present study was conducted utilizing a single‐institution, previously described, retrospective database of patients with SCLC who were treated with WBRT (n = 221). Univariate and multivariate analyses were performed to generate the “brain metastases from SCLC score” (BMS score) based on favorable prognostic factors: Karnofsky performance status (KPS > 70), extracerebral disease status (stable disease/controlled), and time of appearance of BM (synchronous). Furthermore, the disease‐specific graded prognostic assessment score as well as the recursive partitioning analysis (RPA) were performed and compared with the new BMS score by using the log‐rank (Mantel‐Cox) test. Results: BMS score and RPA showed the most significant differences between classes (P < .001). BMS score revealed a mean overall survival (OS) of 2.62 months in group I (0‐1 points), 6.61 months in group II (2‐3 points), and 12.31 months in group III (4 points). The BMS score also identified the group with the shortest survival (2.62 months in group I), and the numbers of patients in each group were most equally distributed with the BMS score. Conclusion: The new BMS score was more prognostic than the RPA and disease‐specific graded prognostic assessment scores. The BMS score is easy to use and reflects known prognostic factors in contemporary patients with SCLC treated with WBRT. Future studies are necessary to validate these findings.

Hypoxic respiratory failure in chronic lung disease

Die Alveolarproteinose ist eine seltene Lungenerkrankung meist mit unklarer Atiologie wobei eine veranderte Surfactanthomoostase zugrunde liegt. Surfactant besteht aus Lipiden und Proteinen, die in Typ-II-Pneumozyten produziert werden. Durch die Reduktion der Oberflachenspannung in den Alveolen spielt Surfactant beim Gasaustausch eine wichtige Rolle. Die Eliminierung des Surfactants erfolgt durch Makrophagen. Entsprechend der Atiologie konnen genetische (insbesondere bei Kindern), autoimmune und sekundare Formen der Alveolarproteinose unterschieden werden. Bei der haufigsten autoimmunen Form (etwa 90 % der Falle) ist eine erhohte Antikorperkonzentration des Anti-Granulozyten-Monozyten-Kolonie-stimulierenden-Faktors (Anti-GM-CSF) zu beobachten, die durch Beeintrachtigung der Clearance zur pathologischen Akkumulation des Surfactants fuhrt [2, 7]. In seltenen Fallen kann die Alveolarproteinose auch als Komplikation anderer Erkrankungen – wie z. B. Silikose mit extremer Staubexposition, Malignome, Chemotherapie, Infektionen oder nach Stammzelltransplantation [6] – auftreten (sekundare Alveolarproteinose). Die klinische Symptomatik ist meistens mild und unspezifisch und besteht aus Dyspnoe, Leistungsschwache und Husten. Die Erkrankung tritt typischerweise bei 40-jahrigen Mannern auf, es besteht eine Assoziation mit dem Rauchen [6]. In der korperlichen Untersuchung sind meistens diffuse Rasselgerausche und Zyanose zu erkennen. Bei dem grosten Teil der Patienten zeigt sich eine restriktive Lungenfunktion mit Verminderung von totaler Lungenkapazitat, forcierter Vitalkapazitat, FEV1 und Diffusionskapazitat. Die Thoraxubersichtsaufnahme (Abb. 2a, b) kann variabel sein, haufig sind diffuse oder fokale bilaterale alveolare Verschattungen mit oder ohne zentraler Verteilung zu erkennen [7]. In einem typischen Fall lassen sich in der CT landkartenartige unterfeldbetonte Areale von milchglasartigen Dichteanhebungen in Kombination mit intra- und interlobularen Septenverdickungen, dem sog. Crazy-paving-Muster, erkennen. Infiltrate und Konsolidierungen konnen auch in verschiedenen Kombinationen zur Darstellung kommen [7]. Mediastinale oder hilare Lymphknotenvergroserungen sind ungewohnlich. Der Verlauf einer Alveolarproteinose ist variabel. Wenn sich die intraalveolar zu Dyspnoe und Hypoxamie fuhrende Menge von Surfactant und surfactantahnlichen Proteine anreichert, ist eine therapeutische Lavage indiziert. Deren Therapieansprechen liegt bei 80 % [7]. In schwereren rezidivierenden Fallen kann uber den Einsatz von Rituximab, einem monoklonalen Anti-CD20-Antikorper gegen B‑Zellen (um die Konzentration der Anti-GM-CSF-Antikorper zu vermindern), oder inhalativem ggf. subkutan injiziertem GM-CSF (um die alveolaren Makrophagen zu stimulieren) diskutiert werden [2, 12]. Die Wirksamkeit einer immunsuppressiven Steroidtherapie ist nicht bewiesen [2]. Open image in new window Abb. 2 Auf der in 2 Ebenen (a, b) im Stehen angefertigten Thoraxubersichtsaufnahme desselben Patienten aus dem Beginn der Erkrankung vor einer der BAL ist eine diffuse bilaterale alveolare Verschattung mit uberlagernden interstitiellen Septenverdickungen zu erkennen. Kein Pleuraerguss