[Vasculitides and eosinophilic pulmonary diseases]. / Vaskulitiden und eosinophile Lungenerkrankungen.

Eosinophilic granulocytes form peripheral effector cells controlled by Th2 lymphocytes, which cause local cell, tissue, and functional disorders of infiltrated organs via the release of cytotoxic basic proteins and oxygen radicals. Diseases associated with eosinophilia include systemic and organ-related forms. The lungs are involved in eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome), acute and chronic eosinophilic pneumonia, as well as in an organ manifestation in hypereosinophilic syndrome and certain parasitic diseases. In particular, the lungs are frequently affected in vasculitis of small vessels, including EGPA, granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). Among these, EGPA is the most frequent pulmonary eosinophil vasculitis representative. In addition, there are various overlap syndromes in which characteristic features of EGPA can be detected in the context of other anti-neutrophil cytoplasmic antibody (ANCA-)associated vasculitides. Occasionally, non-ANCA-associated pulmonary vasculitides occur with eosinophilia (e.g., Schönlein-Henoch purpura, Kawasaki disease, drug-induced hypersensitivity, and paraneoplastic syndrome). Herein, the pulmonary vasculitides accompanying eosinophilia are presented with respect to both the lung manifestations and pulmonary eosinophilia.

[Vasculitides and eosinophilic pulmonary diseases]. / Vaskulitiden und eosinophile Lungenerkrankungen.

Eosinophilic granulocytes form peripheral effector cells controlled by Th2 lymphocytes, which cause local cell, tissue, and functional disorders of infiltrated organs via the release of cytotoxic basic proteins and oxygen radicals. Diseases associated with eosinophilia include systemic and organ-related forms. The lungs are involved in eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome), acute and chronic eosinophilic pneumonia, as well as in an organ manifestation in hypereosinophilic syndrome and certain parasitic diseases. In particular, the lungs are frequently affected in vasculitis of small vessels, including EGPA, granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). Among these, EGPA is the most frequent pulmonary eosinophil vasculitis representative. In addition, there are various overlap syndromes in which characteristic features of EGPA can be detected in the context of other anti-neutrophil cytoplasmic antibody (ANCA-)associated vasculitides. Occasionally, non-ANCA-associated pulmonary vasculitides occur with eosinophilia (e.g., Schönlein-Henoch purpura, Kawasaki disease, drug-induced hypersensitivity, and paraneoplastic syndrome). Herein, the pulmonary vasculitides accompanying eosinophilia are presented with respect to both the lung manifestations and pulmonary eosinophilia.

Lung disease and ulcerative colitis--mesalazine-induced bronchiolitis obliterans with organizing pneumonia or pulmonary manifestation of inflammatory bowel disease?

Ulcerative colitis can be associated with numerous extraintestinal organ manifestations. Pulmonary disease in inflammatory bowel disease (IBD) is supposed to be a rare entity and has to be distinguished from infectious complications and side-effects of medications used in the treatment of IBD. We present the case of a 20-year-old male patient with ulcerative colitis and a 4-week history of respiratory symptoms, malaise, fever and respiratory insufficiency under a medication with mesalazine. Computed tomography showed bilateral subpleural consolidations, bronchoscopy revealed signs of acute bronchitis. The diagnostic work-up ruled out an infectious cause. Under the tentative diagnosis of a mesalazine-induced bronchiolitis obliterans with organizing pneumonia (BOOP) the medication with mesalazine was withdrawn and the patient received a corticosteroid trial. The symptoms quickly improved and prednisone was tapered and stopped after 6 months. Unexpectedly, lung function after complete resolution of respiratory symptoms revealed a residual obstructive ventilatory defect that might be due to an asymptomatic pulmonary manifestation of ulcerative colitis. A review of the literature shows that pulmonary manifestations in IBD as well as pulmonary toxicity of mesalazine might not be as rare as expected and should be included as differential diagnoses in the work-up of respiratory symptoms in patients with IBD. A pragmatic therapeutic approach is reasonable in critically ill patients as it is not always easy to distinguish both entities.

[German guideline for diagnosis and management of idiopathic pulmonary fibrosis]. / S2K-Leitlinie zur Diagnostik und Therapie der idiopathischen Lungenfibrose.

Idiopathic pulmonary fibrosis is a fatal lung disease with a variable and unpredictable natural history and limited treatment options. Since publication of the ATS-ERS statement on IPF in the year 2000 diagnostic standards have improved and a considerable number of randomized controlled treatment trials have been published necessitating a revision. In the years 2006 - 2010 an international panel of IPF experts produced an evidence-based guideline on diagnosis and treatment of IPF, which was published in 2011. In order to implement this evidence-based guideline into the German Health System a group of German IPF experts translated and commented the international guideline, also including new publications in the field. A consensus conference was held in Bochum on December 3rd 2011 under the protectorate of the "Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin (DGP)" and supervised by the "Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften" (AWMF). Most recommendations of the international guideline were found to be appropriate for the german situation. Based on recent clinical studies "weak negative" treatment recommendations for pirfenidone and anticoagulation were changed into "weak positive" for pirfenidone and "strong negative" for anticoagulation. Based on negative results from the PANTHER-trial the recommendation for the combination therapy of prednisone plus azathiorpine plus N-acetlycsteine was also changed into strong negative für patients with definite IPF. This document summarizes essential parts of the international IPF guideline and the comments and recommendations of the German IPF consensus conference.

Interferon-α induced remission in three patients with eosinophilic granulomatosis and polyangiitis. A case study.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic small vessel vasculitis associated with asthma and eosinophilia. Optimal therapy for maintenance of remission is yet to be defined. We present a case-series of three patients with EGPA in whom IFN-α, an immunomodulatory cytokine induced remission, which was maintained even after discontinuation of the drug. In all patients (ages 60, 51, and 50 years), remission was associated with normalisation of eosinophil counts and IgE-levels. Moreover, the patients remained in remission for one to four years. Two patients did not need further immunosuppression, one patient required low dose maintenance therapy. Although reversible side effects occur, IFN-α-therapy induces long-term remission of EGPA even after discontinuation of treatment.

[Therapy for small airways disease: basic principles and therapeutic implications]. / Therapie der kleinen Atemwege: Grundlagen und Möglichkeiten.

This paper describes the possibility of targeting the small airways. In addition to aiding in the therapy for chronic obstructive lung diseases this may prove to be invaluable in the development of treatment strategies for diseases of the bronchioli. Essential factors in peripheral lung deposition include extra-fine particles, a slow and controlled inspiratory flow and an endexspiratory breathhold of 5 - 10 sec (especially for steroids). Due to methodological difficulties, clinical data comparing steroids with larger or extra-fine particles are limited in the field of asthma therapy. However, research suggests a trend for reduced symptoms, positively affected biomarkers and decreased lung hyperinflation when steroids with extra-fine particles are used.

[Lung function diagnostics for the small airways]. / Lungenfunktionsdiagnostik der kleinen Atemwege.

In the recent years growing interest has focused on the involvement of the distal airways (internal diameter < 2 mm) in obstructive lung diseases and other pulmonary conditions. Inflammation in the small airways seems to play a major role in severe and uncontrolled asthma as a major determinant of airflow obstruction. Thus, small airways represent an important target for inhalation therapy. Currently there is no accepted single lung function parameter to detect small airway dysfunction. Various invasive and non-invasive techniques have been described. In future, non-invasive lung function testing will gain more importance. Using spirometry or body plethysmography, lung function parameters such as the ratio of forced vital capacity to slow vital capacity (FVC/SVC) and the residual volume (RV) can provide information about air trapping in small airway disease. Recent data show that techniques such as impulse oscillometry, nitrogen washout testing and analysis of exhaled nitric oxide are promising tools to assess involvement of the small airways. Impulse oscillometry is a sensitive method to calculate peripheral airway resistance, nitrogen washout allows one to detect air trapping and inhomogeneous ventilation in the distal lung, and the alveolar nitric oxide concentration represents a marker of peripheral inflammation. Further studies are needed to validate these functional tests or their combination for diagnosis and assessment of treatment response in pulmonary diseases involving small airways.

[Bronchiolitis. Part 1--anatomic features, classification, clinical presentation and imaging]. / Bronchiolitis. Teil 1--Anatomische Grundlagen, Klassifikation, klinische Präsentation und Bildgebung.

The term "bronchiolitis" refers to a broad spectrum of common conditions related to the small airways associated with a miscellaneous aetiology, histology, clinical features and course. Due to their variability, bronchiolar disorders are generally difficult to diagnose. History (smoking, collagen vascular disease, inhalational injury, medication usage, and organ transplant) may point towards a bronchiolar process. In addition, signs of systemic and pulmonary infection and evidence of air trapping may provide diagnostic hints. Although clinical presentation, physical examination, pulmonary function tests (obstructive ventilatory defect), and plain chest radiographs may demonstrate abnormalities suggesting small airways involvement, they are often non-specific and rarely diagnostic. In contrast, the high-resolution CT (HR-CT) scanning of the chest provides three distinct HR-CT patterns that assist in the diagnosis and differential diagnosis of bronchiolar conditions: (i) a tree-in-bud pattern, (ii) ill-defined centrilobular ground-glass nodules, and (iii) a mosaic attenuation pattern (best visible on expiratory images). The present paper summarises the current knowledge, the classification, imaging, and the clinical presentation of bronchiolar disorders.

[Bronchiolitis]. / Bronchiolitis.

Due to the variability in respect to aetiology, histopathology, lung function, imaging and clinical presentation, as well as overlapping parenchymal processes, bronchiolar disorders are generally difficult to diagnose. Thus, diseases of the small airways should generally be considered in the differential diagnostic approach to respiratory conditions. The diagnostic approach can be devided into several steps: in steps 1 (history and physical examination) and 2 (plain chest radiographs and pulmonary function tests) may point towards a bronchiolar pulmonary process. High-resolution CT (HR-CT) scanning of the chest provides three distinct HR-CT patterns (tree-in-bud sign, ill-defined centrilobular ground-glass nodules and/or pattern of mosaic attenuation, especially visible on expiratory images) which confirm a bronchiolic involvement and help to narrow down a likely diagnosis or more specific bronchiolitic diseases. In inconclusive cases, a histological diagnosis may be required. The paper presents a clinically useful algorithmic approach to diagnosis and differential diagnosis of bronchiolar disorders.

[Airway complications following lung transplantation - clinic, diagnosis, and interventional management]. / Atemwegskomplikationen nach Lungentransplantation - Klinik, Diagnose und interventionelle Behandlung.

Tracheobronchial complications following lung transplantation are defined as local structural or infectious alterations of the airways, which occur early or several months after lung transplantation (LTx). They preferentially develop in the region of the bronchial anastomosis. The most frequently reported complications are bronchial stenosis, bronchial dehiscence, exophytic excessive granulation tissue formation, tracheo-bronchomalacia, bronchial fistulas, and endobronchial infections. Airway complications are mainly attributed to ischaemia of the donor bronchus during the immediate post-transplant period. The most relevant risk factors for the development of airway complications include local infections, surgical techniques, and the immunosuppressive regimen. Thus, management of post-transplant bronchial complications requires early interventional bronchoscopic procedures including balloon bronchoplasty, cryotherapy, laser photoresection, endobronchial brachytherapy, and bronchial stents. In addition, antibiotic treatment, or non-invasive positive-pressure ventilation may be necessary. The procedures required depend on the time of occurrence, the type, and clinical relevance of the airway complication. This review summarises clinical presentation, risk factors, the diagnostic methods as well as management options for the most common LTx-associated airway complications.

[Diagnosis and therapy of pulmonary embolism prior to death]. / Prämortale Diagnostik und Therapie autoptisch bestätigter Lungenarterienembolien.

BACKGROUND: The study was conducted to assess the rate of suspected pulmonary embolism (PE) prior to death and the diagnostic and therapeutic procedures performed. METHODS: Patients with autopsy-confirmed PE between 1998 and 2002 were included. Autopsy register and medical records were reviewed for history, diagnosis and therapy of PE. Patients were categorised into fatal and non-fatal PE according to the autopsy findings. RESULTS: 102 patients with fatal and 247 patients with non-fatal PE were eligible for analysis (median age 68 years; 24-95). In 58.8% with fatal and in 32% with non-fatal PE, disease was suspected pre-mortal. Clinical suspicion of PE was significantly enhanced in venous thrombosis (Odds Ratio [OR] = 12.17, p=0.004) and significantly decreased for chronic vascular disease (OR = 0.30, p=0.002). Recurrent PE was demonstrated in 31.4% fatal and in 4.5% non-fatal PE (OR = 9.81, p=0.001). 7% of all PE were localised centrally, 19% centrally and peripherally and 74% peripherally. Dyspnoea and tachycardia were the most frequent symptoms in fatal PE. About half of all patients suffered from malignancies. Suspicion of PE decreased after day 14 of hospitalisation (OR = 0.33, p=0.021). CONCLUSION: PE often is not diagnosed pre-mortally. Patients with chronic vascular disease and tumours as well as those hospitalised for over 14 days are at particular risk for PE.

[Interferon-alpha as treatment option in severe persistent uncontrolled bronchial asthma: an open label study]. / Interferon-alpha als Therapieoption bei der Behandlung des schwergradig persistierenden, unkontrollierten Asthma bronchiale: Eine offene Studie.

BACKGROUND: The purpose of this study was to evaluate the long-term safety and therapeutic effects of IFN-alpha in patients with severe persistent uncontrolled asthma on long-term oral glucocorticoid (GC) treatment. PATIENTS AND METHODS: The study included 16 patients (2 male, 14 female; age 39 years [range: 24 - 63]) with severe persistent asthma. Diagnosis and severity classification of asthma were established according to the guidelines of the "Deutsche Atemwegsliga". Eight patients stopped the therapy within 7 months due to side effects (n = 3), costs not covered by health insurance (n = 2), non-compliance (n = 2), and change of residence (n = 1). 8 patients (8 female, age 49 years [range: 35 - 68], duration of disease 16 years [range: 5 - 24]) were treated for at least 12 months with IFN-alpha (9 microg) 3 times/week. All patients were on oral glucocorticoids (GCs) for more than 5 years (average dose 17.5 [range: 5.0 - 64.0] mg/d). Clinical signs, lung function, need for reliever medication, number of emergency visits and hospitalisations and diary were assessed prior to and after 12 months of treatment. Data are given as percent of normal or median [range]. RESULTS: IFN-alpha improved lung function after 12 months: FEV1 64 vs. 75 %; FEV1/IVC 76 vs. 89 %; RV 153 % vs. 129 %; Rtot 193 vs. 111 % and morning PEF by 50 - 190 L/min. IFN-alpha also significantly reduced the use of reliever medication (10 [2 - 20] vs. 1 [0 - 3] puffs/d), nocturnal awakening (11 [4 - 30] vs. 1 [0 - 5]/month), emergency visits (7 [2 - 15] vs. 0 [0 - 5]/month) and hospitalisations (4 [1 - 8] vs. 0 [0 - 5]/year). In 5 patients the asthma attacks and nightly disturbances disappeared completely. The improvements were achieved despite a tapering of the oral GCs in all patients from 17.5 (5.0 - 64.0) to 2 (0 - 16) mg/d. In 5 patients GC treatment could be discontinued. The number of blood eosinophils decreased from 0.46 to 0.28 Gpt/L. Adverse events were transient and usually decreased within 3 to 4 weeks. Two patients developed an autoimmune thyreoiditis. CONCLUSION: In severe persistent, uncontrolled, and GC-dependent asthma, treatment with IFN-alpha leads to sustained clinical improvement and allows the reduction or discontinuation of oral GCs. Severe side effects may occur in isolated cases.

Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a pooled analysis.

Bronchial biopsy specimens from chronic obstructive pulmonary disease (COPD) patients demonstrate increased numbers of CD8+ T-lymphocytes, macrophages and, in some studies, neutrophils and eosinophils. Smoking cessation affects the rate of forced expiratory volume in one second (FEV(1)) decline in COPD, but the effect on inflammation is uncertain. Bronchial biopsy inflammatory cell counts were compared in current and ex-smokers with COPD. A pooled analysis of subepithelial inflammatory cell count data from three bronchial biopsy studies that included COPD patients who were either current or ex-smokers was performed. Cell count data from 101 subjects, 65 current smokers and 36 ex-smokers, were analysed for the following cell types: CD4+ and CD8+ T-lymphocytes, CD68+ (monocytes/macrophages), neutrophil elastase+ (neutrophils), EG2+ (eosinophils), mast cell tryptase+ and cells mRNA-positive for tumour necrosis factor-alpha. Current smokers and ex-smokers were similar in terms of lung function, as measured by FEV(1) (% predicted), forced vital capacity (FVC) and FEV(1)/FVC. The results demonstrate that there were no significant differences between smokers and ex-smokers in the numbers of any of the inflammatory cell types or markers analysed. It is concluded that, in established chronic obstructive pulmonary disease, the bronchial mucosal inflammatory cell infiltrate is similar in ex-smokers and those that continue to smoke.

[Global Initiative for Asthma Management and Prevention--GINA 2006]. / Krankheitskontrolle als Therapieprinzip beim Asthma bronchiale.

GINA together with many other national guidelines for the clinical management of asthma recommend a disease severity assessment in order to determine the quantity and frequency of medication. This classification scheme groups patients into one of four categories (intermittent, mild-persistent, moderate-persistent, and severe-persistent). However, it is important to recognise that asthma severity includes both severity of the underlying disease and responsiveness to treatment. In addition, severity is not an unvarying feature in any individual asthma patient and disease severity may change over months or years. Thus, for ongoing asthma management, classification using the level of control may be more relevant and useful in clinical practice. The new version of the GINA guidelines 2006 recognises these limitations of severity assessment and classifies the condition according to the level of control as "controlled", "partly controlled", and "uncontrolled" asthma on the basis of daytime symptoms, restrictions of physical activity, nocturnal symptoms/awakening, need for reliever/rescue medication, lung function (PEF or FEV1) and the frequency of exacerbations. In addition, the patient is assigned to one of five treatment "steps". Each step represents treatment options that are alternatives for controlling asthma. Moreover, steps 1 to 5 provide options of increasing efficacy. In order to maintain asthma control regular monitoring and adjustment is essential. In cases where asthma is not or only partially controlled with the current treatment regimen, step-up treatment is recommended whereas disease control allows a gradual stepping-down to the lowest possible dose of medication necessary to maintain control. This novel asthma management approach based on disease control, may facilitate acceptance and use of asthma guidelines in clinical practice.

[Sonographic diagnosis of post-interventional pneumothorax and hydropneumothorax--prospective study of 100 patients]. / Sonographische Diagnostik des post-interventionellen Pneumothorax und Seropneu- mothorax--Prospektive Studie an 100 Patienten.

In order to answer the question, if transthoracic sonography may replace chest radiographs in diagnosing post-interventional pneumothorax/hydropneumothorax, this prospective study was conducted. A total of 100 patients (38 females, 62 males; median age 63 years), biopsy and 37 had an ultrasound-guided tube thoracostomy, were enrolled in the study. Transthoracic sonography was performed three hours after the intervention, followed by postero-anterior chest radiograph. One (1%) of the 100 patients developed a pneumothorax after transbronchial biopsy. Eight of 37 patients suffered from hydropneumothorax due to tube thoracostomy detected by sonography. In one patient, hydropneumothorax was missed by posteroanterior chest radiography. Sensitivity, specificity and accuracy of transthoracic sonography were 100%. Transthoracic sonography is a safe bed-side-method, allowing an immediate exclusion/diagnosis of postinterventional pneumothorax/hydropneumothorax. The results suggest that chest radiography may only be required in patients with pneumothorax diagnosed by transthoracic sonography so as to assess its extension, if full sonographic assessment is not possible or if any discrepancy exists between TS-results and clinical presentation.

Variability of bronchial inflammation in chronic obstructive pulmonary disease: implications for study design.

There is variability in the distribution of inflammatory cells in bronchial tissue in chronic obstructive pulmonary disease (COPD). Better strategies for biopsy sampling of the airway mucosa may improve the capacity to show a difference between study populations where variability in distribution exists. The current authors have examined sources of biological variability in the quantification of inflammatory cells in endobronchial biopsies using immunostained samples taken from 51 subjects with COPD, with a mean forced expiratory volume in one second of 1.71 L, 55% predicted. The distribution of variance contributed by different sources was similar for different inflammatory cell types. For CD8+ cells, a key inflammatory cell in COPD, the largest contribution to intra-subject variability (39%) was time (i.e. 10 weeks between biopsies of placebo-treated subjects), followed by airway generation (23%), biopsy (2.5%), zone (within section; 1.4%) and section (0.4%). Power calculations demonstrated that examining one section from one biopsy, from each of two airway generations, would require a sample size of 32 subjects per group to show a difference of one doubling or halving in CD8+ cells, compared with 47 subjects per group if only one airway generation was sampled. Therefore, biopsies from more than one airway generation should be examined in order to maximise statistical power to detect a difference between study groups.