[Migration and Tuberculosis]. / Migration und Tuberkulose.

The majority of the people suffering from tuberculosis in Germany are migrants. The treatment of this demographic still presents certain challenges. Only up to a quarter to a fifth of tuberculosis cases in migrants is being diagnosed by the screening methods that were implemented by The German Protection against Infection Act (Infektionsschutzgesetz, IfSG). Reactivation of latent tuberculosis is the most common cause for tuberculosis in migrants. Easy access to health care is vital for the testing and treatment of latent tuberculosis in people with a high risk of reactivation. The level of infection risk, comorbidities and presentation of disease vary depending on the country of origin. Especially during migration people are more susceptible to somatic and mental maladies. Extrapulmonary tuberculosis is frequent in migrants and requires specific diagnostic approaches. Where risk factors for a multi-drug-resistant tuberculosis are present, this condition has to be actively excluded. To facilitate diagnosis and therapy of tuberculosis in migrants a high level of trust has to be established in the doctor-patient relationship. Therefore and despite of cultural and linguistic differences empathy and time are key. Patients need to be encouraged to complete their treatment rather than terminate it prematurely. To that end comorbidities have also to be diagnosed and treated, social and legal aspects have to be considered.

Intra-patient comparison of parietal pleural biopsies by rigid forceps, flexible forceps and cryoprobe obtained during medical thoracoscopy: a prospective series of 80 cases with pleural effusion.

BACKGROUND: There is only few data available on the use of cryotechnique during medical thoracoscopy. METHODS: Medical thoracoscopy was performed in consecutive patients with pleural effusion. Prospectively, biopsies were taken by rigid forceps, flexible forceps and cryoprobe. Specimen size, depth and diagnostic yield were compared. RESULTS: 80 Patients were included. 408 biopsies were taken (205 rigid biopsies, 104 flexible biopsies, 99 cryobiopsies). Mean surface area of rigid biopsies was 22.6 ± 20.4 mm(2) (flexible biopsies: 7.1 ± 9.3 mm(2), cryobiopsies: 14.4 ± 12.8 mm(2)). Rigid biopsies were significantly larger than cryobiopsies (p < 0.001) and flexible biopsies (p < 0.001), crybiopsies were significantly larger than flexible biopsies (p < 0.01). A deep biopsy containing fatty tissue was harvested in 63 % of rigid biopsies (cryobiopsy: 49.5 % flexible biopsy: 39.5 %). In 79/80 cases (98.7 % 95 % CI cannot be calculated) a diagnosis was obtained by rigid biopsy (cryobiopsy: 73/80 cases (91.3 % 95 % CI 86.0 - 96.5 %), flexible biopsy: 74/80 cases (92.5 % 95 % CI 88.6 - 97.4 %)). Diagnostic yield achieved with cryobiopsies was inferior to the yield of rigid biopsies (Difference: 12.7 %), but non-inferior to flexible biopsies (Difference: 6.5 %). CONCLUSION: Cryobiopsies in medical thoracoscopy are safe with high diagnostic yield, non-inferior to flexible biopsies with increased tissue quantity and quality. Cryotechnique can develop an important role in medical thoracoscopy in the near future when rigid thoracoscopy is not available.

[Pneumology and Sports: An Outpatient Endurance Training with Sports Medical Guidance as an Effective Non-pharmacological Therapy in Pneumology - a Feasibility Study]. / Pneumologie und Sport: Ein ambulantes Ausdauertraining mit sportmedizinischer Anleitung als effektive nicht-medikamentöse Therapiemaßnahme in der Pneumologie - eine Projektstudie.

BACKGROUND: In the process of medical rehabilitation muscular endurance training is the main focus. Unfortunately, outpatient rehabilitation opportunities are limited and specialized pulmonary exercise groups ("lung sport groups") rarely available. Therefore we developed an outpatient endurance sports program for patients with respiratory diseases and evaluated its effectiveness. METHODS: In this feasibility study 31 patients (50 ±â€Š15 years) with diverse respiratory diseases were included. By professional functional exercise testing (incl. CPET and lactate measurement according to the standards of DGP and DGSP) the patients optimal training zone was determined and an individualized 12 week lasting aerobic endurance training with ≥ 3 sessions of 20 - 60 min/week realized. RESULTS: After completion of the exercise training program a significant improvement in dyspnoea (Borg-Scale: 65.7 ±â€Š12.2 vs. 62.2 ±â€Š12.6, p = 0.013), body constitution (BMI: 25.7 ±â€Š3.3 vs. 24.3 ±â€Š3.2 kg/m(2), p = 0.018; portion of body fat: 24.8 ±â€Š5.8 vs. 23.8 ±â€Š6.4 %, p = 0.043) as well as physical capacity (VO2 at 4 mmol/l Laktat: 24.2 ±â€Š6.9 vs. 26.5 ±â€Š7.6 ml/min/kg, p < 0.01; performance at 4 mmol/l Laktat: running/walking (n = 14) + 1.1 km/h, p = 0.018 and biking/bicycle ergometer (n = 17) + 8.7 Watt, p = 0.019) was recorded. These positive developments were also observed in mental and physical quality of life (quality of life questionnaire SF-36: physical score + 9.7 points, mental score + 4.5 points). CONCLUSION: The evaluated exercise program can easily be trained by the patient in a self-dependent setting and was seen to be an effective sports medical treatment in patients with diverse pulmonary diseases.

[Pathogenicity of Mycobacterium kansasii]. / Pathogenität von Mycobacterium kansasii.

BACKGROUND: In a recent prospective study on pulmonary infections with non-tuberculous mycobacteria (NTM) led by the WATL group, disease rates in patients with M. kansasii infection were found to be 100 %. In the present study we re-evaluated the pathogenicity of M. kansasii infections in a large lung diseases treatment center in Berlin (Lungenklinik Heckeshorn). METHODS: All patients in whose respiratory specimen cultures M. kansasii was detected between January 2003 and June 2013 were included. The 2007 ATS diagnostic criteria were applied to differentiate disease from asymptomatic infection. The strains were further investigated by sequencing of the 16S-23S rDNA internal transcribed spacer (ITS) region. RESULTS: We evaluated 43 consecutive cases. Complete patient data were available in 38 cases. In one patient, no culture results were obtained, in 37 patients M. kansasii was isolated and patient data could be retrieved. In 25/37 patients (68 %) clinical disease was present so that a specific treatment was initiated (underlying diseases were COPD in 8/25 (32 %), bronchiectasis in 5/25 (20 %), TB scar or scar due to prior chest surgery in 3/25 (12 %) and alcohol abuse in 4/25 (16 %)). Twelve out of 37 patients (32 %) were found to be colonized or asymptomatically infected (underlying diseases were COPD in 7/12 (58 %), bronchiectasis in 3/12 (25 %) and TB scar or scar due to prior chest surgery in 3/12 (25 %)). Sequencing results identified 30 strains as genotype I, and 2 strains as genotype II. In 22/30 cases (73 %) genotype I was considered pathogenic. CONCLUSIONS: In our cohort, we could not confirm the high M. kansasii pathogenicity of 100 % found in a previous multi-center study; we therefore support the clinical and semiquantitative microbiologic diagnostic criteria also for infection with M. kansasii.

[Resistance to second-line drugs in migrants with multidrug-resistant tuberculosis in the Berlin region]. / Resistenzen gegen Zweitlinienmedikamente bei Migranten mit multiresistenter Tuberkulose in der Region Berlin.

The empiric therapy of multidrug-resistant (MDR) tuberculosis (TB) after rapid molecular testing is rendered difficult by an often several weeks-long period of uncertainty, because results of susceptibility testing for second-line TB drugs are pending. The analysis of regional resistance patterns could lead to a more targeted empiric treatment for migrants depending on their country of origin. The results of the susceptibility testing from 2008 to 2013 of all mycobacteria sent to the Institute of Microbiology, working with the department of Pneumology, Heckeshorn Lung Clinic, Berlin, were reanalysed and tested for regional differences. We found 39 multidrug-resistant Mycobacterium tuberculosis strains among the examined strains. More than half of these strains tested susceptible to the following second line drugs namely, linezolid (97%), clofazimine (95%), cycloserine (95%), capreomycin (90%), p-aminosalicylic acid (82%), moxifloxacin (79%) and amikacin (79%). The proportion of strains susceptible to pyrazinamide (44%), ethambutol (28%), prothionamide (15%), rifabutin (8%) and streptomycin (8%) was lower. The mycobacterial cultures of the Chechen patients (n = 14) showed significantly different susceptibilities to amikacin (57%) and prothionamide (36%) compared to the strains from migrants of other regions. In this study, the regional differences in mycobacterial susceptibility to second line drugs suggest that the initial MDR TB therapy of migrants should be tailored to their country of origin.

Physician communication in a lung cancer center--does the message come across?

OBJECTIVE: Lung cancer patients require information about their diagnosis, treatment procedure and the treatment goal. We have examined recall of patients and how satisfied they were with physician communication. PATIENTS AND METHODS: 101 patients with newly diagnosed lung cancer were interviewed shortly after the disclosure of diagnosis about their diagnosis, treatment procedure and treatment goal. Disclosing physicians were asked what information they had given. Physician information and patient recall was then compared. RESULTS: Eighty-six percent (86 of 100 patients) knew their diagnosis, 81% recalled the treatment procedure correctly, and 42% knew if the treatment goal was curative or palliative. We found high satisfaction about communication of diagnosis and treatment procedure (83% resp.77%). However, satisfaction with communication of the treatment goal was 53% (51 of 97 patients) and significantly lower than satisfaction with communication of diagnosis and of treatment procedure. Patients who were informed by male physicians were significantly more satisfied with the disclosure about the treatment goal. CONCLUSIONS: Treatment goals are difficult to convey by untrained physicians. Further research is needed to understand how we can improve patients' understanding of and satisfaction with information about the treatment goal and prognosis and how physicians can improve their communication skills.

[Recommendations for diagnosis and treatment of nontuberculous mycobacterioses of the German Central Committee against tuberculosis and the German Respiratory Society]. / Empfehlungen zur Diagnostik und Therapie nichttuberkulöser Mykobakteriosen des Deutschen Zentralkomitees zur Bekämpfung der Tuberkulose (DZK) und der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin (DGP).

Nontuberculous mycobacterioses comprise a group of diseases caused by mycobacteria which do not belong to the Mycobacterium (M.) tuberculosis complex and are not ascribed to M. leprae. These mycobacteria are characterized by a broad variety as to environmental distribution and adaptation. Some of the species may cause specific diseases, especially in patients with underlying immunosuppressive diseases, chronic pulmonary diseases or genetic predisposition, respectively. Worldwide a rising prevalence and significance of nontuberculous mycobacterioses can be recognized. The present recommendations summarise actual aspects of epidemiology, pathogenesis, clinical aspects, diagnostics - especially microbiological methods including susceptibility testing -, and specific treatment for the most relevant species. Diagnosis and treatment of nontuberculous mycobacterioses during childhood and in HIV-infected individuals are described in separate chapters.

[Diagnostic yield and safety of bronchoscopic cryotechnique in routine diagnostics for suspected lung cancer]. / Diagnostischer Wert und Sicherheit der bronchoskopischen Kryotechnik im Routineeinsatz bei Verdacht auf Lungenkarzinom.

BACKGROUND: Cryoprobes with flexible catheters are an additional important tool for endobronchial interventional therapy and histologic diagnosis. Different studies compared the diagnostic effectiveness and complications to the forceps as a standard. However, routine endoscopic procedures require a combined use of different methods in order to achieve the highest diagnostic yield. We investigated the impact of cryotechnique in comparison with combined diagnostic tools during routine diagnostics of malignant tumors. PATIENTS AND METHODS: A consecutive series of patients undergoing routine diagnostic for lung cancer was included over a 30 months period (n = 469). The use of the cryotechnique, the complication rates and diagnostic value were prospectively documented. Cryotechnique was used on top of conventional technologies. RESULTS: A histologic proof of tumor by cryotechnique in centrally located tumors was delivered more frequently compared to forceps biopsies alone (81.4 versus 59.9% and 66.2 versus 37.7% in peripheral lesions). However, when the other non-cryotechniques were taken into account, the value was reduced in central probes (7.4%; p = 0.02), but remained high for peripheral findings (19.3%; p < 0.002). The frequency of complications seemed unchanged, however severe bleeding occurred. CONCLUSION: The cryotechnique bears high diagnostic potential beside its therapeutic value, also in routine investigations. The changed complication profile of this technology needs to be addressed in the informed consent and secured airway management may be helpful.

[Frequency of thromboembolic complications in patients with lung cancer]. / Häufigkeit thromboembolischer Komplikationen bei Patienten mit Lungenkarzinom.

BACKGROUND: Clinicians are frequently confronted by thromboembolic events in patients with lung cancer, yet few data are available about their incidence. In order to obtain data on the frequency of thromboembolic events in the venous and arterial systems, all patients with lung cancer diagnosed in our hospital were retrospectively evaluated with regard to such an event. PATIENTS/METHODS: All patients with a primary diagnosis of lung cancer between January 2008 and December 2010 were prospectively recorded within our tumour registry and retrospectively evaluated with regard to tumour stage, histology and platinum-based chemotherapy. Thromboembolic complications of the arterial and the venous system were included (pulmonary embolism, deep venous thrombosis, myocardial infarction, mesenterial ischaemia, acute limb ischaemia, ischaemia of the renal artery and ischaemic stroke). RESULTS: Within those 36 months 1940 patients (1209 men, 731 women) were diagnosed with lung cancer. SCLC and NSCLC in 156 (8 %) and 1784 cases (92 %), respectively. Thromboembolic events were documented in 190/1940 (9.8 %) cases, venous thromboembolic complications in 148/190 patients (78 %), arterial thromboembolic complications in 51/190 patients (27 %). We documented 82/148 (55 %) deep venous thrombosis, 98/148 (66 %) pulmonary embolisms and arterial thromboembolic events: ischaemic stroke 23/51 (45 %), coronary arteries 14/51 (28 %), peripheral arteries 12/51 (24 %), mesenterial arteries 4/51 (7.8 %), extracranial cerebral arteries 3/51 (5.9 %). CONCLUSIONS: Thromboembolic complications are a common event in patients with lung cancer. Thus, the benefit of primary prevention anticoagulation in lung cancer patients should be prospectively evaluated.

[Diagnosis and therapy of COPD exacerbation]. / Diagnose und Therapie der COPD-Exazerbation.

The acute exacerbation of COPD (AECOPD) is a life-threatening clinical situation. This review summarizes the definition of AECOPD, the severity assessment, typical clinical signs and symptoms, and refers to clinical pitfalls of diagnosis and therapy. Important aspects of clinical history and physical examination in severe exacerbations are reported. The necessary accompanying examinations like chest X-ray, blood gas analysis, ECG and echocardiography and their differential diagnosis as well as therapeutic significance are described. The most important lab examinations are summarized and controversial parameters, e.g., procalcitonin, are commented upon. The differentiated need for a microbiological sputum screening is emphasized. The authors place special weight on the essential components of the therapeutic management of severe AECOPD. Practical aspects of uncontrolled oxygen therapy, drug selection, and application form of inhalative acute therapy, dose, and duration of glucocorticoids, the indication for antibiotics, mechanical ventilation, and also opiates are summarized.

[Staging with 18F-FDG-PET/CT influences stage-specific survival in advanced non-small cell lung cancer (NSCLC)]. / Der Einfluss des F-18-FDG-PET/CT auf das stadienbezogene Gesamtüberleben beim fortgeschrittenen nicht-kleinzelligen Lungenkarzinom (NSCLC).

BACKGROUND: PET/CT investigation with 18F-fluorodeoxyglucose (FDG) has a high sensitivity (89 - 100 %) and good specificity (79 - 95 %) for the diagnosis of NSCLC. Currently, it is mainly used in preoperative staging. This leads in approximately 15 % of these cases to the diagnosis of metastatic disease that was neither clinically suspected nor seen in previously performed conventional imaging. We hypothesised that including these cases in the palliative stage IV group would have an influence on overall survival. AIM: The aim of this study was to compare the overall survival (OS) of patients with stage IV NSCLC who underwent FDG-PET/CT staging with patients in whom conventional imaging procedures were performed. METHODS: We analysed the OS of all stage IV NSCLC patients diagnosed in our clinic in 2009 (n = 254), 96/254 (38 %) patients were staged with PET/CT and 158/254 (62 %) with conventional imaging (CT group). Survival data were compared by Kaplan-Meier statistics. RESULTS: Patients in the PET/CT group were younger (65 ± 11) than in the CT group (68 ± 10 years; p = 0.008). The median OS of all patients was 246 (range: 217 - 275) days; 338 (range: 247 - 429) days in the PET/CT group and 207 (range: 161 - 253) days in the CT group (p = 0.001), stating a difference of 131 days (4.4 months) in median OS. CONCLUSION: The use of FDG-PET/CT staging mainly in the preoperative setting leads to stage migration of patients with a better prognosis into the worst stage (IV) and thus longer survival within this subgroup. This survival benefit is unrelated to treatment and needs to be addressed in future studies.

[Rational tumour documentation and quality assurance to improve the standard of medical care for lung cancer patients]. / Rationale Tumordokumentation und Qualitätssicherung zur Verbesserung der Versorgungsqualität für Lungenkrebspatienten.

The data on the quality of care of patients with lung cancer in Germany are insufficient. Although the National Lung Cancer Guideline from 2010 provides a good scientific basis for the management of the frequently complex pathways, no evidence exists showing how the relevant guideline recommendations are implemented nationwide or which treatment options generally are chosen in a tumour entity with one of the poorest prognoses. As part of the National Cancer Plan 2008, specific targets have been formulated for the systematic improvement of cancer care in Germany. As a main goal, the national re-organisation and harmonisation of tumor documentation and quality assurance are required for a sustainable improvement in the quality of care. This review article first describes the relevant terms and then examines how the specific targets of the National Cancer Plan have been implemented so far with regard to lung cancer care.

[Curative surgical treatment options for patients with non-small cell lung cancer (NSCLC) and solitary pulmonary metastasis]. / Kurativer chirurgischer Therapieansatz bei solitär pulmonal metastasierten nicht-kleinzelligen Lungenkarzinomen (NSCLC).

INTRODUCTION: The treatment of synchronous solitary lung metastasis in non-small cell lung cancer (NSCLC) remains controversial. Satellite lesions in the same lobe are now classified as T3 which may result in stage IIB (T3N0M0). In contrast, ipsilateral lesions in different lobes are associated with a worse prognosis and classified as T4 tumors (stage IIIA), but operation is usually withheld from these patients. Contralateral lung metastases have been classified more recently as M1a which usually results in a conservative therapy. We analysed survival data of all patients with primary lung tumour and synchronous pulmonary metastasis outside of the tumour-bearing lobe, who underwent surgery. METHODS: Between 1997 - 2007 we operated on 57 patients with NSCLC and simultaneous second (solitary) malignant lesions of the lung, outside of the tumour-bearing lobe, after informed consent. Survival was documented and analysed by Kaplan-Meier statistics (log-rank). RESULTS: The primary tumour was treated in 67 % of cases by lobectomy, in 9 % by pneumonectomy, by bilobectomy in 2 % and in 22 % by segment or wedge resection. The second malignant lesion, and thus potential solitary metastasis, was treated in 83 % by segment or wedge resection. The overall survival of all patients (n = 57) was a median of 82 months (75 - 89 95%CI). In the synchronous second primaries (n = 7) the median survival was 76 months (0.1 to 151 95%CI) and in the synchronous metastases (n = 50) 82 months (95 % CI 75 - 88). This results in a 5-year survival rate of 56 % and 77 %, respectively. The median survival of patients with solitary metastasis, ipsilateral (T4 after UICC7) was 79 months (76 - 82 95 %CI) and with contralateral metastasis (M1a according UICC7) 84 months (60 - 107 95 %CI, p = 0.634). CONCLUSIONS: This analysis shows that patients with solitary pulmonary metastasis (outside of the tumour-bearing lobe) and otherwise operable NSCLC may profit from surgical intervention comprising resection of the primary tumour, lymphadenectomy, and resection of the solitary pulmonary metastasis. Long-term survival can be achieved independent of the localisation of lung metastases (ipsilateral vs. contralateral lung).

[The need for palliative care treatment in pneumology in non-malignant diseases--a case report]. / Bedarf für eine palliativmedizinische Versorgung in der Pneumologie bei nicht malignen Erkrankungen--ein Fallbericht.

A 70-year-old pneumological patient with a COLD for many years, who was using long-term oxygen therapy, developed a complex clinical presentation. During his inpatient course over several weeks we treated severe physical symptoms such as shortness of breath, anxiety and pain. After the transfer to the palliative care ward only an inpatient final accompaniment was possible. In this case the palliative care expertise was integrated too late into the process of the therapy. The delay led to a poorer control of severe physical symptoms such as those named above. Also, the patients request for comprehensive ambulant care could not be realised because the severity of the disease was not detected soon enough. Instruments for the evaluation of the need for an additional palliative care treatment in patients with a non-malignant pneumological disease have not been established sufficiently.

[Implementation of an early geriatric rehabilitation in acute inpatient pneumology]. / Implementierung einer geriatrischen frührehabilitativen Komplexbehandlung (GFK) in der akutstationären Pneumologie.

BACKGROUND: In order to counter the rapidly developing loss of function especially in elderly patients with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) the concept "early geriatric rehabilitation in acute inpatient pneumology" was developed. An essential aspect of the project was a targeted approach making use of multi-professional expertise and standards. METHODS: This 1-year feasibility study included a total of 58 patients with AE-COPD in advanced age (mean: 74.8 ± 6.8 years) with typical geriatric multimorbidity and necessity for acute medical as well as rehabilitation treatment. The results of the early geriatric rehabilitation by a multi-professional rehabilitation team were analyzed in a prospective study approach using standardized assessments. RESULTS: The early geriatric rehabilitation started on median day 3 (range: 1st - 22nd) and lasted in median 16 days (range: 9 - 29). It achieved a significant improvement, particularly in mobility [timed up-and-go, median 19 (range: 10 - 150) vs. 15 (range: 7 - 120) seconds, p < 0.0001], self-help ability [Barthel index, median 73 (range: 5 - 95) vs. 95 (range: 45 - 100) points, p < 0.0001] and social care. CONCLUSIONS: Early geriatric rehabilitation in a cohort of AE-COPD patients is feasible and can be integrated in an acute inpatient pulmonary care system.

Treatment failure in pneumonia: impact of antibiotic treatment and cost analysis.

The aim of this study was to investigate treatment failure (TF) in hospitalised community-acquired pneumonia (CAP) patients with regard to initial antibiotic treatment and economic impact. CAP patients were included in two open, prospective multicentre studies assessing the direct costs for in-patient treatment. Patients received treatment either with moxifloxacin (MFX) or a nonstandardised antibiotic therapy. Any change in antibiotic therapy after >72 h of treatment to a broadened antibiotic spectrum was considered as TF. Overall, 1,236 patients (mean ± SD age 69.6 ± 16.8 yrs, 691 (55.9%) male) were included. TF occurred in 197 (15.9%) subjects and led to longer hospital stay (15.4 ± 7.3 days versus 9.8 ± 4.2 days; p < 0.001) and increased median treatment costs (€2,206 versus €1,284; p<0.001). 596 (48.2%) patients received MFX and witnessed less TF (10.9% versus 20.6%; p < 0.001). After controlling for confounders in multivariate analysis, adjusted risk of TF was clearly reduced in MFX as compared with ß-lactam monotherapy (adjusted OR for MFX 0.43, 95% CI 0.27-0.68) and was more comparable with a ß-lactam plus macrolide combination (BLM) (OR 0.68, 95% CI 0.38-1.21). In hospitalised CAP, TF is frequent and leads to prolonged hospital stay and increased treatment costs. Initial treatment with MFX or BLM is a possible strategy to prevent TF, and may thus reduce treatment costs.

Successful oral desensitization to i.v. para-aminosalicylic acid (PAS) using encapsulated PAS dry substance.

INTRODUCTION: para-Aminosalicylic acid (PAS) is commonly used in the treatment of drug-resistant tuberculosis, including multidrug-resistant tuberculosis. Since its first use in the 1940s, hypersensitivity reactions frequently limit its use in clinical practice. Cases of successful desensitization against PAS using orally administered ascending doses are described in the literature. CASE REPORT: A 25-year-old patient with severe pulmonary multidrug-resistant tuberculosis developed drug fever with rash, acral cyanosis, and shivering immediately after the intravenous application of PAS. Hard gelatine capsules containing PAS dry substance were prepared in order to desensitize this patient. Encapsulated PAS was applied orally in rising doses starting with 10 mg/day and doubling the dose every 2 days until the half-maximal dose of 5,120 mg was reached. Desensitization covers a period of 21 days. Subsequent intravenous application of PAS at the full dose was well tolerated. In a 12-month follow-up period, no more allergic reactions appeared. CONCLUSIONS: PAS dry substance encapsulated in hard gelatine capsules and administered orally in rising concentrations may be useful to archive a successful desensitization for subsequent intravenous applications.