Fatal cases after Omicron BA.1 and BA.2 infection: Results of an autopsy study.

OBJECTIVES: Omicron lineages BA.1/2 are considered to cause mild clinical courses. Nevertheless, fatal cases after those infections are recognized but little is known about risk factors. METHODS: A total of 23 full and three partial autopsies in deceased with known Omicron BA.1/2 infections have been consecutively performed. The investigations included histology, blood analyses, and molecular virus detection. RESULTS: COVID-19-associated diffuse alveolar damage was found in only eight cases (31%). This rate is significantly lower compared with previous studies, including non-Omicron variants, where rates between 69% and 92% were observed. Neither vaccination nor known risk factors were significantly associated with a direct cause of death by COVID-19. Only those patients who were admitted to the clinic because of COVID-19 but not for other reasons had a significant association with a direct COVID-19 -caused death (P >0.001). CONCLUSION: Diffuse alveolar damage still occurred in the Omicron BA.1/BA.2 era but at a considerably lower frequency than seen with previous variants of concern. None of the known risk factors discriminated the cases with COVID-19-caused death from those that died because of a different disease. Therefore, the host's genomics might play a key role in this regard. Further studies should elucidate the existence of such a genomic risk factor.

An Algorithm for Real-Time Pulse Waveform Segmentation and Artifact Detection in Photoplethysmograms.

Photoplethysmography has been used in a wide range of medical devices for measuring oxygen saturation, cardiac output, assessing autonomic function, and detecting peripheral vascular disease. Artifacts can render the photoplethysmogram (PPG) useless. Thus, algorithms capable of identifying artifacts are critically important. However, the published PPG algorithms are limited in algorithm and study design. Therefore, the authors developed a novel embedded algorithm for real-time pulse waveform (PWF) segmentation and artifact detection based on a contour analysis in the time domain. This paper provides an overview about PWF and artifact classifications, presents the developed PWF analysis, and demonstrates the implementation on a 32-bit ARM core microcontroller. The PWF analysis was validated with data records from 63 subjects acquired in a sleep laboratory, ergometry laboratory, and intensive care unit in equal parts. The output of the algorithm was compared with harmonized experts' annotations of the PPG with a total duration of 31.5 h. The algorithm achieved a beat-to-beat comparison sensitivity of 99.6%, specificity of 90.5%, precision of 98.5%, and accuracy of 98.3%. The interrater agreement expressed as Cohen's kappa coefficient was 0.927 and as F-measure was 0.990. In conclusion, the PWF analysis seems to be a suitable method for PPG signal quality determination, real-time annotation, data compression, and calculation of additional pulse wave metrics such as amplitude, duration, and rise time.

Blood pressure monitoring during exercise: comparison of pulse transit time and volume clamp methods.

During physical exercise, pulse transit time (PTT), expressed as the interval between ventricular electrical activity and peripheral pulse wave, may provide a surrogate estimate for blood pressure by the use of specific calibration procedures. The objective of this study was to determine systolic blood pressure (SBP) values derived from the PTT method and from an established method of non-invasive continuous blood pressure measurement based on the volume clamp technique, and to compare their agreement with sphygmomanometry during exercise tests. In 18 subjects, electrocardiogram (ECG) and finger-photoplethysmography were continuously recorded during maximal cycle exercise tests. Intermittent and continuous blood pressure measurements were simultaneously taken using automated sphygmomanometry and a Portapres Model-2 device, respectively. PTT was calculated for each ECG R-wave and the corresponding steepest upstroke slope in the photoplethysmogram, and was transformed to a continuous blood pressure estimate using multipoint nonlinear regression calibration based on the individual subject's sphygmomanometer readings. Bland-Altman limits of agreement between PTT-derived SBP estimates and sphygmomanometer values were -24.7 to 24.1 mmHg, and between Portapres and sphygmomanometer SBP values were -42.0 to 70.1 mmHg. For beat-to-beat SBP estimation during exercise, PTT measurement combined with multipoint nonlinear regression calibration based on intermittent sphygmomanometry may be an alternative to volume clamp devices.

Blood pressure monitoring during exercise: Comparison of pulse transit time and volume clamp methods.

During physical exercise, pulse transit time (PTT), expressed as the interval between ventricular electrical activity and peripheral pulse wave, may provide a surrogate estimate for blood pressure by the use of specific calibration procedures. The objective of this study was to determine systolic blood pressure (SBP) values derived from the PTT method and from an established method of non-invasive continuous blood pressure measurement based on the volume clamp technique, and to compare their agreement with sphygmomanometry during exercise tests. In 18 subjects, electrocardiogram (ECG) and finger-photoplethysmography were continuously recorded during maximal cycle exercise tests. Intermittent and continuous blood pressure measurements were simultaneously taken using automated sphygmomanometry and a Portapres Model-2 device, respectively. PTT was calculated for each ECG R-wave and the corresponding steepest upstroke slope in the photoplethysmogram, and was transformed to a continuous blood pressure estimate using multipoint nonlinear regression calibration based on the individual subject's sphygmomanometer readings. Bland-Altman limits of agreement between PTT-derived SBP estimates and sphygmomanometer values were -24.7 to 24.1 mmHg, and between Portapres and sphygmomanometer SBP values were -42.0 to 70.1 mmHg. For beat-to-beat SBP estimation during exercise, PTT measurement combined with multipoint nonlinear regression calibration based on intermittent sphygmomanometry may be an alternative to volume clamp devices.

Pulmonary pulse transit time: a novel echocardiographic indicator of hemodynamic and vascular alterations in pulmonary hypertension and pulmonary fibrosis.

INTRODUCTION: Pulse transit time (PTT) is generally assumed to be a surrogate marker for blood pressure changes and arterial stiffness. The aim was to evaluate whether pulmonary PTT (pPTT) may be noninvasively measured by Doppler echocardiography and whether it might be valuable for detecting pulmonary hemodynamic and vascular alterations. METHODS: We defined pPTT as the interval between R-wave in the ECG and the corresponding peak late systolic pulmonary vein flow velocity measured by pw-Doppler in the pulmonary vein. Twelve consecutive patients with pulmonary hypertension (PH) and 12 subjects without any cardiovascular or respiratory disease were included in the study. All patients underwent a standard echocardiography including pPTT measurement. RESULTS: In the PH group, 5 patients had idiopathic pulmonary arterial hypertension (WHO 1), 1 patient PH associated with connective tissue disease (CTD, WHO 1) without pulmonary fibrosis (PF), and 6 patients PH associated with PF either due to CTD (WHO 1) or other etiology (WHO 3). Mean pPTT was significantly shorter in the PH group (138.0 ± 16.78 msec; P < 0.0001) than in the control group (383.5 ± 23.84 msec). Within the PH group, the subgroup of patients with PF showed significantly shorter mean pPTT (93.50 ± 15.47 msec; P = 0.004) than the subgroup of patients with PH without PF (182.6 ± 14.35 msec). CONCLUSIONS: The results of this study suggest that pPTT might be an interesting surrogate marker of pulmonary hemodynamic and vascular alterations in PH and PF. Further studies are warranted to evaluate the possible influence of other variables on pPTT.

Relation of exercise capacity with lung volumes before and after 6-minute walk test in subjects with COPD.

INTRODUCTION: There is growing evidence that exercise-induced variation in lung volumes is an important source of ventilatory limitation and is linked to exercise intolerance in COPD. The aim of this study was to compare the correlations of walk distance and lung volumes measured before and after a 6-min walk test (6MWT) in subjects with COPD. METHODS: Forty-five subjects with stable COPD (mean pre-bronchodilator FEV1: 47 ± 18% predicted) underwent a 6MWT. Body plethysmography was performed immediately pre- and post-6MWT. RESULTS: Correlations were generally stronger between 6-min walk distance and post-6MWT lung volumes than between 6-min walk distance and pre-6MWT lung volumes, except for FEV1. These differences in Pearson correlation coefficients were significant for residual volume expressed as percent of total lung capacity (-0.67 vs -0.58, P = .043), percent of predicted residual volume expressed as percent of total lung capacity (-0.68 vs -0.59, P = .026), inspiratory vital capacity (0.65 vs 0.54, P = .019), percent of predicted inspiratory vital capacity (0.49 vs 0.38, P = .037), and percent of predicted functional residual capacity (-0.62 vs -0.47, P = .023). CONCLUSIONS: In subjects with stable COPD, lung volumes measured immediately after 6MWT are more closely related to exercise limitation than baseline lung volumes measured before 6MWT, except for FEV1. Therefore, pulmonary function testing immediately after exercise should be included in future studies on COPD for the assessment of exercise-induced ventilatory constraints to physical performance that cannot be adequately assessed from baseline pulmonary function testing at rest.

Effects of nasal positive expiratory pressure on dynamic hyperinflation and 6-minute walk test in patients with COPD.

INTRODUCTION: Dynamic hyperinflation is an important target in the treatment of COPD. There is increasing evidence that positive expiratory pressure (PEP) could reduce dynamic hyperinflation during exercise. PEP application through a nasal mask and a flow resistance device might have the potential to be used during daily physical activities as an auxiliary strategy of ventilatory assistance. The aim of this study was to determine the effects of nasal PEP on lung volumes during physical exercise in patients with COPD. METHODS: Twenty subjects (mean ± SD age 69.4 ± 6.4 years) with stable mild-to-severe COPD were randomized to undergo physical exercise with nasal PEP breathing, followed by physical exercise with habitual breathing, or vice versa. Physical exercise was induced by a standard 6-min walk test (6 MWT) protocol. PEP was applied by means of a silicone nasal mask loaded with a fixed-orifice flow resistor. Body plethysmography was performed immediately pre-exercise and post-exercise. RESULTS: Differences in mean pre- to post-exercise changes in total lung capacity (-0.63 ± 0.80 L, P = .002), functional residual capacity (-0.48 ± 0.86 L, P = .021), residual volume (-0.56 ± 0.75 L, P = .004), S(pO2) (-1.7 ± 3.4%, P = .041), and 6 MWT distance (-30.8 ± 30.0 m, P = .001) were statistically significant between the experimental and the control interventions. CONCLUSIONS: The use of flow-dependent expiratory pressure, applied with a nasal mask and a PEP device, might promote significant reduction of dynamic hyperinflation during walking exercise. Further studies are warranted addressing improvements in endurance performance under regular application of nasal PEP during physical activities.

Histology as a potential clinical predictor of outcome in advanced non-small-cell lung cancer treated with vinorelbine and mitomycin combination chemotherapy.

BACKGROUND: The importance of clinical predictors in the treatment of non-small-cell lung cancer (NSCLC) has increased during the last decade. This retrospective study analyzed the combined patient-level data from two phase II trials that investigated the efficacy and safety of combination chemotherapy with vinorelbine and mitomycin in patients with locally advanced or metastatic NSCLC. The aim of this analysis was to determine if patients' baseline and disease characteristics, including histology, gender, smoking history, and expression of TTF-1, might be potential predictors of outcome. METHODS: Response rates, unadjusted survival times, and Cox covariate-adjusted hazard ratios (HRs) were calculated. Results were reported separately for each subgroup in each individual trial and in the pooled data set. RESULTS: A total of 175 patients were included in this analysis. Adjusted HRs for both overall survival (OS) and progression free survival (PFS) favored the nonadenocarcinoma histology subgroup, achieving a statistical significance for OS in the pooled data (n = 175; HR 0.68; 95 % CI 0.49-0.94; p = 0.019). TTF-1-negative immunohistochemistry was associated with a significantly higher response rate (25 vs. 0 %; p = 0.04) and with a nonsignificant advantage in OS (n = 33; HR 1.23; 95 % CI 0.56-2.73; p = 0.608). Gender and smoking history were not strongly related to outcome. CONCLUSIONS: The results of this analysis indicate that patients with nonadenocarcinoma histology might get superior benefit from combination chemotherapy with vinorelbine and mitomycin. These results should be confirmed in a prospective study.

Isolated IgG4-related interstitial lung disease: unusual histological and radiological features of a pathologically proven case.

IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP).We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy.Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD.

Omalizumab in patients with severe asthma: the XCLUSIVE study.

BACKGROUND AND AIMS: Although the efficacy and safety of omalizumab (OMA) in uncontrolled severe allergic asthma has been demonstrated in several randomised controlled trials (RCTs), information on the treatment in a practice-related setting is limited. Thus, the purpose of this prospective multi-centre study (XCLUSIVE) was to investigate the efficacy, compliance and utilisation of OMA therapy in real-life clinical practice in Germany. METHODS: One hundred ninety-five asthmatic patients initiated on anti-Immunoglobulin E (IgE) IgE treatment were followed-up for 6 months. Forced expiratory volume in 1 s (FEV(1) ), exacerbation rate, days of absence, asthma symptoms [Asthma Control Questionnaire (ACQ)], a Global Evaluation of Treatment Effectiveness (GETE) and medication use were assessed. RESULTS: Measured outcome variables improved after a 16-week treatment period with OMA (FEV(1) +13.7% predicted P < 0.05, exacerbation rate -74.9% P < 0.0001, days of absence -92.1% P < 0.001, ACQ -43.7% P < 0.0001). Investigators evaluated the effectiveness of OMA by GETE in 78.8% as excellent or good (responder), and in 12.6%/8.6% as moderate/poor or worse (non-responder). Responders demonstrated better improvement of FEV(1), exacerbation rate, days of absence, ACQ and reduction of oral corticosteroids compared with non-responders. CONCLUSION: Results of effectiveness strongly suggest that the efficacy demonstrated in RCTs can be transposed to a clinical practice-related setting.

Circulating biomarkers of tissue remodelling in pulmonary hypertension.

OBJECTIVE: Besides persisting high pulmonary arterial pressure and increased pulmonary vascular resistance, remodelling of pulmonary tissues and subsequently the right heart are the key pathomechanisms of pulmonary hypertension (PH). Extracellular matrix maintenance in this context plays a central role. METHODS: We tested the hypothesis that plasma concentration of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinases (TIMP)-4 and tenascin C (TNC) might be useful as biomarkers for assessing the severity of PH. Therefore, the concentrations of MMP-2, TIMP-4, TNC and N-terminal b-type natriuretic peptide (NT-proBNP) of 36 PH patients were compared with those of 44 age- and gender-matched healthy volunteers. Additionally, lung function, 6-min walk distance and right heart function were assessed. RESULTS: In PH patients, significantly elevated plasma levels of MMP-2, TIMP-4, TNC and NT-proBNP were detected. In particular, TIMP-4 was significantly increased in patients with higher NYHA classification, and in patients with severe right ventricular hypertrophy. CONCLUSION: Monitoring of plasma TIMP-4 and to a lesser extent of MMP-2 and TNC levels in PH patients might help to assess the beneficial effects of PH pharmacotherapy on tissue remodelling.

Cryoprobe biopsy increases the diagnostic yield in endobronchial tumor lesions.

OBJECTIVE: Forceps biopsy is the standard method to obtain specimens in endoscopically visible lesions. It is common to combine forceps biopsy with cytology methods to increase the diagnostic yield. Although the flexible cryoprobe has been established for bronchoscopic interventions in malignant stenosis, the obtained biopsies, called "cryobiopsies," have not been investigated in a large cohort of patients. The aim of this feasibility study was to prospectively evaluate the diagnostic yield and safety of cryobiopsy and forceps biopsy. METHODS: During a 6-year period, 296 patients with visible endoluminal tumor lesions were included in the study at the bronchoscopy unit of a university hospital. In the first consecutively conducted 55 cases, both techniques, forceps biopsy and cryobiopsy, were applied simultaneously. Pathologic and quantitative image analyses were performed to evaluate the size and quality of the obtained specimens. We evaluated the safety and diagnostic yield to describe the feasibility of cryobiopsy. RESULTS: Comparative analysis of the first conducted and randomly assigned 55 cases revealed a significantly higher diagnostic yield for cryobiopsy compared with forceps biopsy (89.1% vs 65.5%, P < .05). In this cohort, quantitative image analysis showed significantly larger biopsies regarding size and artifact-free tissue sections for cryobiopsy compared with forceps biopsy (P < .0001). The overall diagnostic yield of cryobiopsy was 89.5%. Mild bleeding occurred in 11 cases (3.7%), moderate bleeding occurred in 3 cases (1.0%), and severe bleeding occurred in 1 case (0.3%). CONCLUSION: Cryobiopsy is safe and increases the diagnostic yield in endobronchial tumor lesions. The method also is feasible under routine conditions.

Endobronchial tumor debulking with a flexible cryoprobe for immediate treatment of malignant stenosis.

OBJECTIVE: In addition to use of a laser, argon plasma coagulation, electrocautery, or coring with a rigid bronchoscope, tumor debulking with a flexible cryoprobe is used for therapeutic bronchoscopy with an immediate effect for endobronchial pathologies. We performed this analysis to determine the usefulness, efficacy, and safety of the flexible cryorecanalization in a large population under routine conditions. METHODS: We identified 225 bronchoscopic interventions that were done as cryorecanalization with a flexible cryoprobe. All patients had symptomatic airway stenosis. We determined the endoscopic success rate and safety (bleeding and perforation) of the procedure. RESULTS: Successful cryorecanalization was achieved in 205 (91.1%) of 225 patients. The flexible cryoprobe was used with all patients, in most patients in combination with flexible bronchoscopy and only in a minority (n = 31, 13.8%) in combination with a rigid bronchoscope. Additional interventional techniques used were endobronchial stents (n = 11, 4.9%) and argon plasma coagulation (n = 37, 16.4%). Mild bleeding (if ice-cold NaCl or epinephrine solution was necessary) occurred in 9 (4.0%) patients, moderate bleeding (if argon plasma coagulation or a bronchus blocker was required) occurred in 18 (8.0%) patients, and severe bleeding (events with hemodynamic instability) never occurred. CONCLUSIONS: Cryorecanalization with the flexible cryoprobe for treatment of symptomatic endobronchial tumor stenosis is a safe technique with a high success rate and immediate treatment effect.

Detection of bone metastases in patients with lung cancer: 99mTc-MDP planar bone scintigraphy, 18F-fluoride PET or 18F-FDG PET/CT.

PURPOSE: The aim of the study was to compare the diagnostic accuracy of (18)F-fluorodeoxyglucose (FDG) PET/CT versus standard planar bone scintigraphy (BS) and (18)F-labelled NaF ((18)F) PET for the detection of bone metastases (BM) in non-small cell lung cancer (NSCLC). METHODS: (18)F-FDG PET/CT was performed in 126 patients with NSCLC. Within 7 days BS (n = 58) or (18)F PET (n = 68) was performed. (18)F-FDG PET/CT, BS and (18)F PET were evaluated by two experienced readers. Lesions were graded on a scale from 1 (definite BM) to 5 (degenerative lesion), and equivocal lesions were determined as indifferent (grade 3). RESULTS: A total of 92 patients showed degenerative lesions (grade 4/5) on PET/CT, BS or (18)F PET. In 34 patients (27%) BM lesions were diagnosed (grades 1 and 2). In 13 of 18 patients BM were concordantly diagnosed with PET/CT and (18)F PET. PET/CT showed more BM compared to (18)F PET (53 vs 40). In one patient one osteolytic BM was false-negative on (18)F PET. However, (18)F PET identified four patients with BM compared to negative findings on PET/CT. Of 16 patients, 11 had concordant findings of BM on PET/CT and BS. In three patients BS was false-negative and in two patients BM were diagnosed as indifferent. CONCLUSION: Integrated (18)F-FDG PET/CT is superior to BS in the detection of osteolytic BM in NSCLC. Thus, PET/CT may obviate the need to perform additional BS or (18)F PET in the staging of NSCLC, which significantly reduces costs.

Efficacy and safety of combination chemotherapy with mitomycin and vinorelbine for the treatment of advanced non-small cell lung cancer.

BACKGROUND: Aim of this study was to evaluate efficacy, toxicity and tolerability of chemotherapy with a combination of mitomycin and vinorelbine (M/V) in patients with advanced non-small cell lung cancer (NSCLC). METHODS: We enrolled 110 patients (median age 67 years) with locally advanced or metastatic NSCLC, who had no prior chemotherapy or progressive disease after at least one prior chemotherapy regimen. 45 patients (41%) were > or =70 years old. All patients received vinorelbine 25mg/m(2) (d1,8) and mitomycin 8mg/m(2) (d1) every 3-4 weeks. Restaging was performed by CT-scan after every two courses M/V according to RECIST criteria. RESULTS: M/V was well tolerated, even in patients with a poor performance status or > or =70 years Median progression free survival was 4.4 months. Median overall survival was 9.0 months with a 1-year survival rate of 39%. Partial response was observed in 15% and stable disease in 51% of patients. Both hematological and non-hematological toxicities were generally mild. CTC grade 3 toxicities observed included neutropenia in 3%, anemia in 3%, thrombocytopenia in 1% and suspected pneumonitis in 2% of patients. Except neutropenia in 2% and acute dyspnea in 1%, there were no other grade 4 toxicities and no treatment associated casualties. There was no relevant difference in outcome or toxicity between patients > or =70 and <70 years. CONCLUSIONS: M/V seems to be a well-tolerated and effective chemotherapy regimen with low toxicity in patients with advanced NSCLC. It seems to be an interesting option even for patients > or =70 years or with a reduced performance status.

[Enzyme replacement therapy in Pompe's disease]. / Schwere chronische respiratorische Insuffizienz bei adulter Glykogenose Typ II (Morbus Pompe). Erfolgreiche Therapie mittels Enzymersatz.

BACKGROUND: Pompe's disease, a rare, inherited deficiency of the enzyme alpha-1,4-glucosidase (GAA), is a lysosomal storage disorder. Early-onset (infantile) Pompe's disease is associated with cardiomegaly and severe myopathy and, if left untreated, will inevitably lead to death within the first 2 years of life. In juvenile Pompe's disease, progression of the disease is generally slower and involvement of the myocardium is less likely with onset at a later age. The adult form of Pompe's disease is frequently associated with a progressive proximal myopathy which is more marked in the lower limbs. Involvement of the respiratory system is common. A new treatment with intravenous enzyme replacement (Myozyme) is now available. At present, there is only limited data available regarding its efficacy in the treatment of the adult form of Pompe's disease. CASE REPORT: A 67-year-old lady with Pompe's disease and known severe respiratory compromise due to involvement of the respiratory muscles had had recurrent emergency admissions with respiratory failure. After only a few weeks of treatment with intravenous enzyme replacement with Myozyme, significant improvement in her respiratory function was noticed. Following a total length of treatment of 7 months, her arterial blood gas results on room air had almost returned to normal. CONCLUSION: A glycogen storage disorder (type II) should be excluded in all adult patients with a slowly progressive weakness involving pelvic and thigh muscles even when respiratory involvement is not present. In addition to supportive treatment, a new enzyme replacement therapy for patients with late-onset disease has now become available which shows promising results.

[Erdheim-chester disease: a rare cause of interstitial lung disease]. / Erdheim-Chester-Erkrankung: seltene Ursache einer interstitiellen Lungenerkrankung.

BACKGROUND: Erdheim-Chester disease is a rare non-Langerhans' cell histiocytosis of unknown etiology with typical osteosclerotic long-bone findings. However, clinical symptoms are mostly due to disease involvement of other tissues, particularly of the lung, heart and retroperitoneum. CASE REPORT: A 58-year-old man presented with fatigue, diffuse pain of the lower extremities, dyspnea, and a dry cough. Physical examination was unremarkable. Chest X-ray revealed an extensive bilateral pulmonary inter interstitial process. Computed tomography demonstrated pulmonary fibrosis, periaortic fibrosis of the thoracic aorta, and retroperitoneal fibrosis. The diagnosis of Erdheim-Chester disease was confirmed by minimally invasive lung biopsy. Steroid therapy was not tolerated. Following a stable interval of 18 months there was a disease progression, which could be stabilized after the initiation of cyclophosphamide therapy. CONCLUSION: In patients with extensive pulmonary fibrosis and coincidence of other organ manifestations such as periaortic or retroperitoneal fibrosis and particularly in case of symmetrical osteosclerotic bone lesions, Erdheim-Chester disease should be considered. Immunosuppressive therapy can lead to a stabilization or even improvement of the disease.