[Eosinophilic Granulomatosis with Polyangiitis with Pulmonary and Cardiac Involvement]. / Eosinophile Granulomatose mit Polyangiitis mit pulmonaler und kardialer Beteiligung.

A 62-year-old patient with bronchial asthma and chronic rhinosinusitis underwent inguinal hernia surgery. After the operation, sudden circulatory arrest occurred, requiring cardiopulmonary resuscitation. Coronary angiography revealed a 99 % proximal stenosis of right coronary artery (RCA) with unsuspicious and smooth coronary vessel walls. In the further course, several similar events occurred, but without pathological findings in the coronary angiography. Initially, echocardiography showed slightly reduced left ventricular ejection fraction of 45 %. Chest radiography revealed bilateral pulmonary infiltrates, and white blood cell count showed severe eosinophilia (37 %). Serological antibody testing including ANA, ENA and c-/p-ANCA was negative. Myeloproliferative pathologies were excluded by bone marrow puncture. The patient suffered from emerging dyspnea, weakness, and ongoing weight loss. A methylprednisolone pulse of 250 mg/d for 3 days remained without significant effect, so that the patient was eventually referred to our university hospital due to ongoing clinical deterioration. On admission, the patient suffered from weakness, progressive muscular atrophy, and dyspnea on exertion. Physical examination revealed a right-sided peroneal paralysis. Bronchial lavage detected severe eosinophil alveolitis (37 %), and laboratory findings showed elevated cardiac enzymes and NT-proBNP (Troponin-T > 700 ng/l, NT-proBNP > 10.000 ng/l). Echocardiography revealed a dramatic deterioration of cardiac function (LVEF 16 %). Interdisciplinary discussion between pulmonologists and cardiologists lead to the diagnosis of ANCA-negative eosinophilic granulomatosis with polyangiitis (EGPA) with pulmonary and cardiac involvement. Initiation of immunosuppressive therapy with methylprednisolone 1000 mg/d for 3 days followed by cyclophosphamide therapy (6 pulses, administered every 4 weeks) led to substantial symptomatic improvement, complete regression of pulmonary infiltrates and marked recovery of cardiac function (LVEF 47 %). CONCLUSION: Serological detection of elevated ANCAs is not necessary for diagnosis of EGPA. Only 30 - 70 % of patients are positive for these, particularly if neurological and/or renal rather than cardiac and/or pulmonary involvement is present. This may be a pitfall in establishing the correct diagnosis. Induction therapy with cyclophosphamide is the preferred treatment for steroid-refractory EGPA with life-threatening organ involvement.

Lobe-wise assessment of lung volume and density distribution in lung transplant patients and value for early detection of bronchiolitis obliterans syndrome.

PURPOSE: To evaluate quantitative computed tomography (CT) measurements of the lung parenchyma in lung transplant (LTx) patients for early detection of the bronchiolitis obliterans syndrome (BOS). MATERIALS AND METHODS: 359 CT scans of 122 lung transplant patients were evaluated. Measurements of lung volume and density were performed for the whole lung and separately for each lobe. For longitudinal analysis the difference between the baseline at 6 months after LTx and follow-up examinations was calculated. Patients with and without BOS (matched 1:2) were compared at two different time points, the last examination before the BOS onset and the first examination within one year after BOS onset. RESULTS: 30 patients developed BOS during the follow-up period. Longitudinal changes in the lung volume and lung density measured on CT differed significantly between those patients with and without early BOS, in particular the difference of the inspiratory and expiratory lung volume (p < 0.001), the ratio of the expiratory and inspiratory lung volume (p < 0.001-p = 0.001) and MLD (p < 0.001-p = 0.001), the volume on expiration (p < 0.001-p = 0.007), the MLD on expiration (p < 0.001-p = 0.007), and the percentiles on expiration (p < 0.001-p = 0.002) with an increase of lung volume and a decrease of lung density. Changes were pronounced in the lower lobes. Before BOS onset, patients with and without future development of BOS showed no significant differences. CONCLUSION: Longitudinal changes of lung volume and lung density measured on CT start markedly at BOS onset with increased lung volume and decreased lung density indicating increased inflation levels. Even though this method may help to diagnose BOS at onset it is not useful as a predictor for BOS before disease onset.

Endobronchial Ultrasound in Suspected Non-Malignant Mediastinal Lymphadenopathy.

BACKGROUND: Endobronchial ultrasound (EBUS) bronchoscopy with transbronchial needle aspiration (TBNA) is a well-established tool in mediastinal staging in lung cancer and gains importance in exploration of non-malignant lymphadenopathy. The aim of this study was to evaluate the role of EBUS-TBNA in suspected non-malignant diseases. METHODS: A retrospective, single-center, observation analysis of endobronchial ultrasound bronchoscopy procedures was performed in a university medical center between March 2013 and July 2015. All patients with suspected non-malignant mediastinal lymphadenopathy were included. Cytopathological and microbiological results of EBUS were compared to clinical diagnosis 6 months after procedure and performance of EBUS was contrasted to malignant indications. RESULTS: During study period, 333 EBUS bronchoscopies in 315 patients with mediastinal lymphadenopathy were performed. 111 out of 315 (35 %) patients had neither primary signs nor history of a malignant disease, categorised as patients with suspected non-malignant disease. 245 lymph nodes were sampled (median size 15 mm [IQR10 - 19]). Preferred station for TBNA was lymph node station 7 (38 %). Cytopathological findings revealed non-specific inflammation (n = 81; 70 %), carcinoma (n = 7; 6 %), epithelioid cell granulomas (n = 20; 17 %). 7 samples (6 %) were non-representative. Microbiologic testing of lymph nodes identified 3 infections (Mycobacteria tuberculosis [n = 2] and Nocardia nova [n = 1]) relevant to antibiotic therapy. Minor adverse events were observed in 9 out of 115 (8 %) patients. Sensitivity of EBUS-TBNA intervention in suspected non-malignant disease was 76 % and specificity 96 %. CONCLUSIONS: EBUS-TBNA revealed a specific cause for suspected non-malignant lymphadenopathy in one-third of cases and was associated with excellent specificity. Predominant specific causes were granuloma, besides from tumor. In 3 patients pathogen could be isolated by TBNA.

"White-Out" After Lung Transplantation: A Multicenter Cohort Description of Late Acute Graft Failure.

Graft failure represents a leading cause of mortality after organ transplantation. Acute late-onset graft failure has not been widely reported. The authors describe the demographics, CT imaging-pathology findings, and treatment of patients presenting with the latter. A retrospective review was performed of lung transplant recipients at two large-volume centers. Acute late-onset graft failure was defined as sudden onset of bilateral infiltrates with an oxygenation index <200 without identifiable cause or concurrent extrapulmonary organ failure. Laboratory, bronchoalveolar lavage (BAL), radiology, and histology results were assessed. Between 2005 and 2016, 21 patients were identified. Median survival was 19 (IQR 13-36) days post onset. Twelve patients (57%) required intensive care support at onset, 12 (57%) required mechanical ventilation, and 6 (29%) were placed on extracorporeal life support. Blood and BAL analysis revealed elevated neutrophilia, with CT demonstrating diffuse ground-glass opacities. Transbronchial biopsy samples revealed acute fibrinoid organizing pneumonia (AFOP), organizing pneumonia, and diffuse alveolar damage (DAD). Assessment of explanted lungs confirmed AFOP and DAD but also identified obliterative bronchiolitis. Patients surviving to discharge without redo transplantation (n = 2) subsequently developed restrictive allograft syndrome. This study describes acute late-onset graft failure in lung allograft recipients, without known cause, which is associated with a dismal prognosis.

Phenotyping Chronic Lung Allograft Dysfunction Using Body Plethysmography and Computed Tomography.

Restrictive subtype of chronic lung allograft dysfunction (CLAD) was recently described after lung transplantation. This study compares different definitions of a restrictive phenotype in CLAD patients and impact on survival. Eighty-nine CLAD patients out of 1191 screened patients (September 1987 to July 2012) were included as complete longitudinal lung volume measurements and chest computed tomography (CT) after CLAD onset was available. CT findings and lung volumes were quantified and survival was calculated for distinctive groups and predictive factors for worse survival were investigated. Graft survival in patients with total lung capacity (TLC) between 90% and 81% of baseline (BL) (n = 13, 15%) in CLAD course was similar to those with TLC >90% BL (n = 64, 56%; log-rank test p = 0.9). Twelve patients (13%) developed a TLC ≤80% BL and 10 (11%) had significant parenchymal changes on CT, of whom 6 (46%) also had TLC ≤80% BL. CT changes correlated with TLC ≤80% BL (Φ-coefficient = 0.48, p = 0.001). Patients with either TLC ≤80% or significant CT changes (n = 16, 18%) had a significantly reduced survival (log-rank p < 0.001). Forced vital capacity loss at CLAD onset was associated with poorer survival but did not correlate with the TLC or CT changes. A restrictive subtype of CLAD may be defined by either TLC ≤80% BL or severe parenchymal changes on chest CT.

[Chronic rejection: Differences and similarities in various solid organ transplants]. / Chronische Abstoßung: Unterschiede und Ähnlichkeiten bei verschiedenen soliden Organtransplantationen.

In this paper, chronic rejections after transplantation of the lungs, heart, liver, and kidney are described. Chronic allograft dysfunction (CAD) plays an important role in all of these transplantations and has a significant influence on patient survival. The pathophysiological reasons for CAD varies greatly in the various organs.Chronic lung allograft dysfunction (CLAD) is the most important determinant of survival and quality of life after lung transplantation. Diagnosis is based on lung function, especially forced expiratory flow in 1 s (FEV1) decline. Prevention, early detection, and rapid treatment are extremely important. Azithromycin and extracorporeal photopheresis are commonly used for treatment because they usually positively influence the progression of lung remodeling.The expression for chronic rejection of the heart is cardiac allograft vasculopathy (CAV). Immunological and nonimmunological factors are important for its development. Due to limited therapeutic options, prevention is of utmost importance (administration of mTOR inhibitors and minimizing cardiovascular risk factors).The mid- and long-term survival rates after liver transplantation have hardly changed in recent decades, which is an indication of the difficulty in diagnosing chronic graft dysfunction. Chronic ductopenic rejection accounts for a small proportion of late graft dysfunction. Idiopathic posttransplant hepatitis and de novo autoimmune hepatitis are important in addition to recurrence of the underlying disease that led to transplantation.Chronic allograft nephropathy is the result of severe rejection which cumulates in increasing fibrosis with remodeling. The earliest possible diagnosis and therapy is currently the only option. Diagnosis is based on evidence of donor-specific antibodies and histological findings.

Phenotyping established chronic lung allograft dysfunction predicts extracorporeal photopheresis response in lung transplant patients.

Chronic lung allograft dysfunction (CLAD) remains the leading cause of mortality in lung transplant recipients after the first year. Treatment remains limited and unpredictable. Existing data suggests extracorporeal photopheresis (ECP) may be beneficial. This study aimed to identify factors predicting treatment response and the prognostic implications. A single center retrospective analysis of all patients commencing ECP for CLAD between November 1, 2007 and September 1, 2011 was performed. In total 65 patients were included, 64 of whom had deteriorated under azithromycin. Median follow-up after commencing ECP was 503 days. Upon commencing ECP, all patients were classified using proposed criteria for emerging clinical phenotypes, including "restrictive allograft syndrome (RAS)", "neutrophilic CLAD (nCLAD)" and "rapid decliners". At follow-up, 8 patients demonstrated ≥10% improvement in FEV1 , 27 patients had stabilized and 30 patients exhibited ≥10% decline in FEV1 . Patients fulfilling criteria for "rapid decliners" (n=21, p=0.005), RAS (n=22, p=0.002) and those not exhibiting neutrophilia in bronchoalveolar lavage (n=44, p=0.01) exhibited poorer outcomes. ECP appears an effective second line treatment in CLAD patients progressing under azithromycin. ECP responders demonstrated improved progression-free survival (median 401 vs. 133 days). Proposed CLAD phenotypes require refinement, but appear to predict the likelihood of ECP response.

[Innervation of the airways in asthma bronchiale and chronic obstructive pulmonary disease (COPD)]. / Neuronale Kontrolle bei chronisch entzündlichen und obstruktiven Lungenerkrankungen wie Asthma bronchiale und COPD.

Airway nerves have the capacity to control airway functions via neuronal reflexes and through neuromediators and neuropeptides. Neuronal mechanisms are known to play a key role in the initiation and modulation of airway hyperresponsiveness and inflammation. Therefore, the nerve fibres may contribute to airway narrowing in asthma and COPD. In addition to the traditional transmitters such as norepinephrine in postganglionic sympathetic nerve fibres and acetylcholine in parasympathetic nerve fibres, a large number of neuropeptides have been identified to have different pharmacological effects on the muscle tone of the vessels and bronchi, mucus secretion and immune cells. Meanwhile, a broad range of stimuli including capsaicin, bradykinin, hyperosmolar saline, tobacco smoke, allergens, ozone, inflammatory mediators and even cold, dry air have been shown to activate sensory nerve fibres to release neuropeptides such as the tachykinins substance P (SP) and neurokinin A (NKA) to mediate neurogenic inflammation. Different aspects of the neurogenic inflammation have been well studied in animal models of chronic airway inflammation and anticholinergic agents such as ipratropium bromide (Atrovent (®)) and tiotropium bromide (Spiriva (®)) have been proved to be important when used as bronchodilators for the treatment of obstructive airway diseases such as COPD. However, little is known about the role of neurogenic airway inflammation in human diseases. In this review, we address the current knowledge of the airway sensory nerves in human asthma and COPD.

Catheter fragmentation and local lysis in two lung transplant patients with pulmonary embolism.

In conjunction with the rising number of lung transplant operations in the past decade, an increased predisposition to venous thrombosis (VT), particularly within the first year posttransplantation has been observed. Previous studies have revealed that between 8.6% and 12% of patients develop VT, which can ultimately result in pulmonary emboli (PE).Transplanted lungs pose a much greater infarction risk due to their lack of collateral vascularisation, relying entirely on the vasa publica--the pulmonary artery--in the absence of vasa privata. Such losses in viable lung parenchyma are always serious, but carry still greater risks for single-lung transplant recipients, an early diagnosis and treatment remain critical. Here we report on two cases of PE after lung transplantation, both of whom were managed with catheter fragmentation and local thrombolysis. In our opinion, this approach represents a viable treatment for symptomatic PE in lung transplant recipients. The benefits and risks of the alternative treatment options in these special cases will be reviewed and the definitive therapy was described. In the patients treated, catheter fragmentation with localized thrombolysis resulted in short term improvements in graft function, but could not prevent later lung infarction in one case.