Peripheral Arterial Tonometry in Pulmonary Vasculitis.

Vascular wall inflammation in primary vasculitides results in diminished vessel dilation and finally impaired blood flow, causing multiple organs dysfunction and ultimate damage. In granulomatosis with polyangiitis (GPA), the inflammatory process concerns small and medium sized vessels and its pulmonary location is often predominant. The pivotal role in the development of that pathology plays vascular endothelium. Endothelial vasodilatory function strongly depends on the instant production and release of nitrogen oxide (NO), a potent local factor controlling vascular tonus. NO output is triggered by a variety of stimuli, especially by ischemia. The endothelial vasodilatory ability can be measured indirectly by a few of methods, one of them is peripheral arterial tonometry (PAT). The method assesses reactive hyperemia, mediated mostly by NO release, as a response to vessel occlusion. The vasodilatory reaction depends on the quality of the endothelium which deteriorates with time of GPA disease progression. The aim of the present study was to estimate a correlation between the clinical status, reflected by the disease extent index (DEI), and the vasodilatory endothelial function reflected by the index of arterial reactive hyperemia (RHI), measured by PAT in 27 patients with GPA, having a significant pulmonary involvement. We found a moderate inverse correlation between DEI and log-transformed RHI (r = -0.46, p < 0.05). The conclusion is that impaired endothelial function, as assessed by RHI-PAT, might predict the GPA progression.

Whooping Cough in Adults: A Series of Severe Cases.

Bordetella pertussis is a gram-negative aerobic coccobacillus causing contagious respiratory tract disease called whooping cough. The virulence factors consist of pertussis toxin, filamentous hemagglutinin, fimbriae, lipooligosaccharide, and adenylate cyclase toxin. The disease causes a worldwide threat to public health despite a high vaccination coverage. The course of whooping cough in adults is frequently atypical, causing difficulty in diagnosis. In this report we present five patients hospitalized with Bordetella pertussis infection manifesting atypical and severe symptoms. The diagnosis was based on serological tests: serum concentration of specific antibodies against pertussis toxin and sputum cultures. We observed a wide spectrum of symptoms, from benign (sinus pain - 80 %, headaches - 20 %), through moderate (hemoptysis - 40 %; chest pain 60 %) to severe symptoms (cardiac arrhythmia - 40 %; syncope - 60 %). Bordetella pertussis infection can cause life-threatening complications and exacerbation of concomitant chronic diseases. Most vaccination programs cover only the first few months of life. Booster doses should be considered in adults, especially those immunocompromised or with pulmonary complications, but also in healthcare workers who are exposed to the contagion and also may spread the infection.

Clostridium Difficile Infection Due to Pneumonia Treatment: Mortality Risk Models.

One of the most common gastrointestinal infection after the antibiotic treatment of community or nosocomial pneumonia is caused by the anaerobic spore Clostridium difficile (C. difficile). The aim of this study was to retrospectively assess mortality due to C. difficile infection (CDI) in patients treated for pneumonia. We identified 94 cases of post-pneumonia CDI out of the 217 patients with CDI. The mortality issue was addressed by creating a mortality risk models using logistic regression and multivariate fractional polynomial analysis. The patients' demographics, clinical features, and laboratory results were taken into consideration. To estimate the influence of the preceding respiratory infection, a pneumonia severity scale was included in the analysis. The analysis showed two statistically significant and clinically relevant mortality models. The model with the highest prognostic strength entailed age, leukocyte count, serum creatinine and urea concentration, hematocrit, coexisting neoplasia or chronic obstructive pulmonary disease. In conclusion, we report on two prognostic models, based on clinically relevant factors, which can be of help in predicting mortality risk in C. difficile infection, secondary to the antibiotic treatment of pneumonia. These models could be useful in preventive tailoring of individual therapy.

Antibiotic Treatment of Hospitalized Patients with Pneumonia Complicated by Clostridium Difficile Infection.

Clostridium difficile infection (CDI) is one of the most common gastrointestinal complication after antimicrobial treatment. It is estimated that CDI after pneumonia treatment is connected with a higher mortality than other causes of hospitalization. The aim of the study was to assess the relationship between the kind of antibiotic used for pneumonia treatment and mortality from post-pneumonia CDI. We addressed the issue by examining retrospectively the records of 217 patients who met the diagnostic criteria of CDI. Ninety four of those patients (43.3 %) came down with CDI infection after pneumonia treatment. Fifty of the 94 patients went through severe or severe and complicated CDI. The distribution of antecedent antibiotic treatment of pneumonia in these 50 patients was as follows: ceftriaxone in 14 (28 %) cases, amoxicillin with clavulanate in 9 (18 %), ciprofloxacin in 8 (16.0 %), clarithromycin in 7 (14 %), and cefuroxime and imipenem in 6 (12 %) each. The findings revealed a borderline enhancement in the proportion of deaths due to CDI in the ceftriaxone group compared with the ciprofloxacin, cefuroxime, and imipenem groups. The corollary is that ceftriaxone should be shunned in pneumonia treatment. The study demonstrates an association between the use of a specific antibiotic for pneumonia treatment and post-pneumonia mortality in patients who developed CDI.

Antibiotic Treatment of Hospitalized Patients with Pneumonia Complicated by Clostridium Difficile Infection.

Clostridium difficile infection (CDI) is one of the most common gastrointestinal complication after antimicrobial treatment. It is estimated that CDI after pneumonia treatment is connected with a higher mortality than other causes of hospitalization. The aim of the study was to assess the relationship between the kind of antibiotic used for pneumonia treatment and mortality from post-pneumonia CDI. We addressed the issue by examining retrospectively the records of 217 patients who met the diagnostic criteria of CDI. Ninety four of those patients (43.3 %) came down with CDI infection after pneumonia treatment. Fifty of the 94 patients went through severe or severe and complicated CDI. The distribution of antecedent antibiotic treatment of pneumonia in these 50 patients was as follows: ceftriaxone in 14 (28 %) cases, amoxicillin with clavulanate in 9 (18 %), ciprofloxacin in 8 (16.0 %), clarithromycin in 7 (14 %), and cefuroxime and imipenem in 6 (12 %) each. The findings revealed a borderline enhancement in the proportion of deaths due to CDI in the ceftriaxone group compared with the ciprofloxacin, cefuroxime, and imipenem groups. The corollary is that ceftriaxone should be shunned in pneumonia treatment. The study demonstrates an association between the use of a specific antibiotic for pneumonia treatment and post-pneumonia mortality in patients who developed CDI.

Angiogenic activity of sera from interstitial lung disease patients in relation to pulmonary function.

OBJECTIVE: Chronic inflammation and fibrosis are characteristic of interstitial lung diseases (ILD) and are accompanied by neovascularisation. The aim of this study was to examine the relationship between the angiogenic activity of sera from ILD patients and pulmonary function tests. MATERIAL AND METHODS: Serum samples were obtained from 225 ILD patients: 83 with sarcoidosis, 31 with idiopathic pulmonary fibrosis, 29 with extrinsic allergic alveolitis, 16 with collagen vascular diseases, 13 with scleroderma with pulmonary manifestations (SCL), 14 with Wegener's granulomatosis (WG), 12 with silicosis, 12 with pulmonary Langerhans cells histiocytosis, 10 with drug-induced pulmonary fibrosis, 5 with cryptogenic organizing pneumonia, and 36 healthy volunteers. An animal model of leukocyte induced angiogenesis assay was used as an angiogenic test. In all patients spirometry, whole body plethysmography, static lung compliance, and single breath diffusing capacity of the lungs for carbon monoxide (DLco) were performed. RESULTS: The angiogenic properties of sera from ILD differed, depending on the disease. In the examined ILD, the most important functional disturbances were decreases in static compliance and DLco. The correlation between DLco and angiogenic activity of sera was observed (P<0.05). CONCLUSIONS: The data show that sera from ILD patients constitute a source of mediators modulating angiogenesis. Angiogenic activity of sera of ILD patients is related to DLco.

Rhinologic and sinonasal changes in PR3 ANCA pulmonary vasculitis.

BACKGROUND: Over 70-95% patients with PR3 ANCA pulmonary vasculitis present with upper respiratory tract symptoms or sings. Nasal cavity usually presents with obstruction and chronic refractory infections (rhinosinusitis) which commonly manifest as bloody discharge or crusting obstruction. Mucopurulent discharge may occur in the acute phase or remission, along with other symptoms suggesting sinusitis. Later on, saddle nose deformities can occur due to collapse of the nasal septum. Other common destruction areas are the maxillary ostia, erosion of the tubinates or damage of soft palate. OBJECTIVE: The aim of the study was to characterize pathologies of nasal and sinonasal CT scans in patients with PR3 pulmonary ANCA vasculitis and to establish the CT diagnostic criteria for WG. Between 2005-2009 sinonasal CT visualization was performed in 35 patients (19 female, 16 male) with PR3 ANCA positive WG. RESULTS: Bony destruction of the nasal cavity was revealed in 15 (42.8%), damage or distortion of the paranasal sinuses in 20 (57.1%), the mastoid cells in 7 (20%), and the orbits in 7 (20%) patients. Sclerosing osteitis of the nasal cavity and paranasal sinuses were observed in 11 (31.4%) and in 24 (68.5%), respectively. Bony thickening of the nasal cavity was shown in 5 (14.2%) patients and of the paranasal sinuses in 7 (20%) (unilateral in 2 and bilateral in 5 patients). Seven patients (20%) had orbital masses; all unilateral. Septal perforation was observed in 11 (31.4%) and saddle nose deformity in 7 (20%) patients. CONCLUSIONS: Maxillary sinuses are regions which are most frequently affected during the course of PR3 ANCA pulmonary vasculitis. CT imagines may be a useful supplement to clinical and activity scoring of WG disease with pulmonary involvement.

Angiogenic activity of sera from interstitial lung disease patients in relation to clinical and radiological changes.

OBJECTIVE: Clinical symptoms and radiological changes are useful in monitoring patients with interstitial lung diseases (ILD). Neovascularization participates in the pathogenesis of idiopathic pulmonary fibrosis and other ILD. The objective of the study was to examine the relationships between angiogenic activity of sera from ILD patients and clinical or radiological status. MATERIAL AND METHODS: Serum samples were obtained from 83 patients with sarcoidosis, 31 with idiopathic pulmonary fibrosis (IPF), 29 with hypersensitivity pneumonitis (HP), 16 with collagen diseases with pulmonary manifestation (CD), 13 with scleroderma (SCL), 14 with Wegener's granulomatosis (WG), 12 with pulmonary Langerhans cell histiocytosis (HIS), 12 with pneumoconiosis (PNC), 10 with drug-induced lung disease (DLD), 5 with cryptogenic organizing pneumonia (COP), and from 36 healthy volunteers. As an angiogenic test we used a cutaneous angiogenesis assay according to Sidky and Auerbach. Clinical status was evaluated using a special questionnaire. In all patients chest radiographs were performed. RESULTS: The angiogenic properties of sera from ILD differed depending on the clinical diagnosis. The strongest proangiogenic effect was induced by sera from patients with HP (mean number of new vessels 16.8), CD (16.6), sarcoidosis (16.3), IPF (16.2), and PNC (15.7). In the case of DLD (13.2), the effect was comparable to healthy controls (13.5). In contrast, sera from SCL (mean number of the vessels 10.5) and HIS patients (10.8) significantly inhibited angiogenesis compared with controls. The angiogenic activity of sera from patients with hilar or mediastinal lymph nodes involvement was higher than that of sera from patients with lung fibrosis. There were also differences in the serum angiogenic activity in relation to the severity of dyspnea. CONCLUSIONS: The data showed that sera from ILD patients constitute a source of mediators modulating angiogenesis, but the pattern of reaction is different in various diseases. Sera from HP, sarcoidosis, IPF, and CD patients demonstrated the strongest proangiogenic activity. However, sera from SCL and HIS inhibit angiogenesis. Angiogenic activity of examined sera was related to the clinical and radiological changes.

Co-trimoxazole and prevention of relapses of PR3-ANCA positive vasculitis with pulmonary involvement.

BACKGROUND: Bacterial and viral respiratory tract infections may trigger relapses in patients with PR3-positive vasculitis. Data have suggested that treatment with co-trimoxazole may be beneficial, because this antibiotic could act by eliminating the offending microbe and thereby stopping the initiating stimulus. GOAL AND METHODS: Prospective, randomized, placebo-controlled study of the efficacy of co-trimoxazole given 960 mg thrice weekly for 18 months in preventing relapses in patients with Wegener's granulomatosis (WG) in remission, after treatment with cyclophosphamide and prednisolone was conducted. Relapses and infections were assessed with predefined criteria based on clinical, laboratory, serological, microbiological, and histopathological findings. Sixteen patients were assigned to receive co-trimoxazole and 15 to receive placebo. RESULTS: Seventy five percent of the patients in the co-trimoxazole group remained in remission at 18 months and 55% of those in the placebo group. A proportional hazard regression analysis identified a positive PR3-ANCA test at the start of treatment, chronic nasal crusting, and Staphylococus aureus infection as risk factors for relapse. Furthermore, the analysis identified treatment with co-trimoxazole as an independent factor associated with prolonged disease-free interval. CONCLUSION: Treatment with co-trimoxazole reduces the incidence of relapses in patients with Wegener's granulomatosis in remission.

Clinical implications of serum thrombomodulin in PR3-ANCA-associated vasculitis.

BACKGROUND: Vascular injury is the main mechanism in pathophysiology of PR3-ANCA-associated vasculitis. Soluble serum thrombomodulin (sTM) is a membrane-bound receptor for thrombin expressed by vascular endothelial cells. - OBJECTIVE: The aim of study was to determine the blood levels of sTM in patients with PR3-ANCA-associated vasculitis. MATERIAL AND METHODS: Twenty five patients with Wegener's granulomatosis (WG), 13 with generalized WG and 12 with limited WG, with histologically proven disease, and 15 healthy subjects as a control were investigated. An ELISA for detection of sTM and PR3-ANCA was performed. The disease activity was evaluated according to BVAS and DEI indexes. RESULTS: Significant increases in sTM were found in both active generalized and limited active WG compared with control values: 108 +/- 12, 56 +/- 2, and 12 +/- 4 ng/ml, respectively. Elevated ANCA titer correlated with disease activity, but more weakly than sTM levels did. Elevated sTM concentration is a result of vascular endothelial injury in the course of PR3-ANCA associated vasculitis. CONCLUSIONS: Soluble serum thrombomodulin is a promising, both diagnostic and therapeutic, marker of endothelial cell injury in relation to disease activity and progression in autoimmune disorders, reflecting the degree of endothelial cell damage.

Modulatory effect of sera from patients with various types of pulmonary fibrosis on mononuclear cell induced angiogenesis in relation to pulmonary function.

Angiogenesis plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. Pulmonary fibrosis occurs also in many diseases, such as other types of interstitial pneumonias or drug-induced pulmonary fibrosis. The aim of the study was to examine the effect of sera from patients with various types of pulmonary fibrosis on angiogenesis induced by human mononuclear cells (MNC) in relation to lung functions. The study population consisted of 32 patients with idiopathic pulmonary fibrosis (IPF), 11 patients with drug-induced pulmonary fibrosis (DIPF), 6 with cryptogenic organizing pneumonia (COP), and 20 healthy volunteers. An animal model of leukocyte-induced angiogenesis assay was used as an angiogenic test. Spirometry, whole-body plethysmography, static lung compliance (Cst), and diffusing capacity of the lung for CO (DL(CO)) were performed in all patients. Sera from IPF and COP patients significantly stimulated angiogenic activity of MNC, compared with sera from healthy donors and from DIPF patients (P<0.001). However, sera from healthy donors and DIPF significantly stimulated angiogenic activity of MNC compared with the control group with PBS (P<0.001). In all groups, a decrease in the mean value of Cst and DL(CO) was observed, but no significant correlation between VC, FEV(1), DL(CO), Cst, and angiogenic activity of sera from examined patients was found. Sera obtained from patients with pulmonary fibrosis constitute a source of mediators modulating angiogenesis, but the pattern of reaction is different in various diseases. The strongest reaction is observed in IPF and the weakest one in DIPF. The angiogenic activity of sera did not correlate with the pulmonary function of patients with pulmonary fibrosis.

Angiogenic activity of sera from silicosis and pulmonary Langerhans cell histiocytosis patients in relation to lung function tests.

Angiogenesis has been implicated in the pathogenesis of interstitial lung diseases. A correlation between serum angiogenic cytokines level of patients with idiopathic pulmonary fibrosis and radiographic manifestations or functional pulmonary changes has been described, but the role of angiogenesis in the pathogenesis of other interstitial lung diseases such as silicosis and pulmonary Langerhans cell histiocytosis remains unclear. The aim of the study was to examine the effect of sera from silicosis and pulmonary Langerhans cell histiocytosis patients on angiogenesis induced by human mononuclear cells (MNC) in relation to pulmonary function. The study population consisted of 12 patients with silicosis, 12 patients with pulmonary Langerhans cell histiocytosis (PLH), and 14 healthy volunteers. Spirometry, whole-body plethysmography, static lung compliance (Cst), and diffusing capacity of the lung for CO (DL(CO)) were performed in all patients. As an angiogenic test, leukocyte induced angiogenesis assay according to Sidky and Auerbach was used. Sera from PLH patients exerted a significant inhibitory effect on angiogenesis (P<0.001). Sera from silicosis patients significantly (P<0.001) stimulated angiogenesis compared with sera from healthy donors. However, sera from healthy donors significantly stimulated the angiogenic activity of MNC compared with the control with PBS. The mean value of DL(CO) was significantly lower in the group of patients with PLH compared with patients with silicosis (P<0.05). A significant correlation between angiogenesis index and DL(CO) was observed (P<0.05). No significant correlation between the angiogenesis index and other functional parameters was found. Sera from interstitial lung diseases patients and healthy donors constitute a source of mediators modulating angiogenesis. Sera from silicosis patients stimulate neovascularization but sera from PLH patients exert an inhibitory effect on angiogenesis. A correlation between serum angiogenic activity and DL(CO) was found.

Angiogenic activity of sera from patients with systemic autoimmune diseases in relation to clinical, radiological, and functional pulmonary status.

Systemic autoimmune diseases, such as vasculitis and collagen diseases, are characterized by chronic inflammation. Mutual interrelationship between angiogenesis and chronic inflammation has already been demonstrated. The aim of the study was to examine the effect of sera from patients with systemic autoimmune diseases on angiogenesis induced by human mononuclear cells. The study population consisted of 43 patients with a systemic autoimmune disease associated with pulmonary manifestations, divided into three groups: 14 with Wegener's granulomatosis (WG), 13 with systemic sclerosis (SS), and 16 with collagen vascular diseases (CVD) such as rheumatoid arthritis, systemic lupus erythematosus, and dermatomyositis. The control group consisted of 15 healthy volunteers. Clinical status was evaluated using a questionnaire. Standard chest radiographs were performed in all patients. Pulmonary function tests were performed according to the ERS standards. An animal model of a leukocyte-induced angiogenesis assay was used as an angiogenic test. Sera from WG and CVD patients significantly stimulated angiogenesis compared with healthy subjects (P<0.001). On the other hand, sera from healthy donors exerted a proangiogenic effect compared with PBS. In contrast, sera from SS patients significantly (P<0.001) inhibited angiogenesis compared with sera from healthy subjects and PBS. Proangiogenic effect of sera from systemic diseases patients depended on radiological changes. No significant correlation between a degree of dyspnea or functional pulmonary tests and the number of new vessels or angiogenesis index was found. Sera from patients with systemic autoimmune diseases and healthy people constitute the source of mediators modulating angiogenesis. These modulatory effects differ depending on the disease entity.

Chronic crusting, nasal carriage of Staphylococcus aureus and relapse rate in pulmonary Wegener's granulomatosis.

Wegener's granulomatosis is a systemic disease characterized by necrotizing granulomatous inflammation of the upper and lower respiratory tract and necrotizing crescentic glomerulonephritis. Nasal carriage of S. aureus is considered a risk factor for S. aureus infections. The aim was to examine possible risk factors for relapse including refractory nasal carriage of Staphylococcus aureus in patients with Wegener's granulomatosis. Swab cultures from anterior nares for S. aureus were taken in consecutive patients (n=28), with limited (n=15) and systemic forms (n=13) of biopsy-proven Wegener's granulomatosis. The occurrence of infection and relapses were identified according to defined criteria. Seventeen of the 28 patients (60%: 95% Cl, 41-76%) were found to be chronic nasal carriers of S. aureus (> or =80% of nasal cultures positive for S. aureus). A hazard regression analysis identified chronic nasal carriage of S. aureus as independent risk factor for relapse (HR-4.56; Cl 2.45-7.65) in patients with limited Wegener's granulomatosis. Chronic nasal carriage of S. aureus characterized patients with Wegener's granulomatosis, who are more prone to relapses.

Association between clinical activity and high-resolution tomography findings in pulmonary Wegener's granulomacytosis.

Wegener's granulomatosis is characterized histologically by necrotizing granulomatous angitis that most commonly involves the upper, lower respiratory tract, and kidneys, but may affect any organ system. The aim of the study was to assess the usefulness of high-resolution computed tomography (HRCT) for evaluating pulmonary disease activity in Wegener's granulomatosis patients. Pulmonary disease activity at the time of examination was scored in 66 patients with Wegener's granulomatosis according to clinical, radiological, and bronchoscopic findings: activity group (n=43, Group 1), past activity group (n=14, Group 2). Of 66 staging examinations, 57 (86%) revealed abnormal CT scans: masses or nodules (30 patients in Group 1 and 6 patients in Group 2, parenchymal opacifications (15 in Group 1 and 1 in Group 2), pleural irregularity (3 in Group 1 and 10 in Group 2). We conclude that HRCT may be a useful supplement to clinical scoring of disease activity in Wegener's granulomatosis with pulmonary involvement.

Procalcitonin as an indicator of systemic response to infection in active pulmonary Wegener's granulomacytosis.

Differential diagnosis of infection during active immune disease, such as Wegener's granulomatosis (Wegener's granulomatosis), is a major clinical challenge. Laboratory measures, erythrocyte sedimentation rate or C-reactive protein, can be elevated in infections that supervene, or coinciding with, in active Wegener's granulomatosis, and thus are nonspecific. The aim of the study was to compare the serum levels of procalcitonin (PCT) in patients with active and inactive disease. Twenty two sera were tested from 10 patients with active, generalized, and biopsyproven Wegener's granulomatosis, with pulmonary involvement, and 12 patients with nonactive one. PCT levels were measured using an immunoluminometric assay. The PCT level was markedly elevated (1.2-3.6 ng/ml) in 9 of the 10 sera from active and 2 of the 12 sera from nonactive Wegener's granulomatosis. PCT levels were in the normal range (0.28-0.56 ng/ml) in the remaining patients with nonactive Wegener's granulomatosis. We conclude that serum procalcitonin levels may be a potentially useful marker in the diagnosis of bacterial infection supervening in active Wegener's granulomatosis.

Correlation between Helicobacter pylori infection and pulmonary Wegener's granulomacytosis activity.

Wegener's granulomatosis is a clinicopathologic entity of unknown origin characterized histologically by necrotizing granulomatous angiitis that affects any organ system. The disease most commonly involves the upper and lower respiratory tract and kidneys. Wegener's granulomatosis is a disease which requires a long-term use of steroids and NSAIDs. Because of that patients frequently develop gastroduodenal mucosal lesions and concurrent Helicobacter pylori infection. The aim of the study was to assess the impact of H. pylori infection on clinical features in patients with Wegener's granulomatosis treated with non-steroidal anti-inflammatory drugs, steroidal drugs, and cyclophosphamide. Thirty six patients with systemic Wegener's granulomatosis were tested for the presence of H. pylori infection and 25 of them turned up H. pylori positive. The severity of Wegener's granulomatosis disease, prevalence of gastroduodenal lesions, and the type and duration treatment seem to depend upon H. pylori infection.

TNFalpha and INFgamma inducing capacity of sera from patients with interstitial lung disease in relation to its angiogenesis activity.

Sera from interstitial lung diseases (ILD) constitute a source of mediators participating in angiogenesis. The nature of these mediators is unknown. The aim of our study was to asses whether preincubation with sera from ILD patients could influence TNFalpha and INFgamma production by normal mononuclear cells (MNC) challenged with LPS (for TNFalpha) or PHA (for INFgamma), and to correlate the cytokine levels with angiogenic properties of sera. The study population consisted of 53 patients with ILD, 16 with sarcoidosis (SAR), 11 with avian fanciers' lung (AFL), 10 with scleroderma with pulmonary manifestations (SCL), 9 with Wegener's granulomatosis (WG), and 7 with pulmonary Langerhans' cell histiocytosis (PLH). As a control, sera from 10 healthy volunteers were used. Neovascularization was measured by a leukocyte-induced angiogenesis assay according to Sidky and Auerbach. TNFalpha and INFgamma production was estimated by a one-step culture immunoassay CytoTraptrade mark TNFalpha DIA (Biosource Europe S.A.) after 3 h of incubation with LPS (TNFalpha) and 24 h incubation with PHA (INFgamma). Sera from sarcoidosis patients, WG patients, and AFL patients significantly stimulated angiogenesis in comparison with sera from healthy donors (P<0.001). Sera from PLH and SCL patients presented anti-angiogenic properties in comparison with sera from healthy donors and from each examined group (P<0.001). Comparing with other groups, preincubation with sera from AFL and WG patients led to a significant increase in TNFalpha production by normal MNC. Highly significant correlation between serum angiogenic activity and TNFalpha production by MNC was observed in SCL, WG, and AFL (r=0.74, P<0.01). we conclude that TNFalpha may play an important role in neovascularization in ILD.

Antibody response to inactivated subunit influenza vaccine in patients with Wegener's granulomatosis.

In the present study we investigated the humoral response to inactivated subunit influenza vaccine in patients with Wegener's granulomatosis, who were in clinical and serological remission after immunosuppressive treatment (Group I). The results were compared with patients with Wegener's granulomatosis who were treated immunosuppressively, but were not vaccinated (Group II) and with healthy persons who received the vaccine (Group III). After vaccination, antihemagglutinin and antineuraminidase antibody titers significantly increased in Groups I and Group III subjects when compared with the pre-vaccination values. Post-vaccination protection rates ranged from 51.4% to 74.3% in Group I patients and from 65.7% to 94.3% in Group III subjects. In Group II, the protection rates were between 0% and 21.4%. The response rates ranged from 60% to 74.3% in Group I patients and from 71.4% to 88.6% in Group III subjects. In Group II, the response rates were between 7.1% and 21.4%. The study confirmed the immunogenicity of influenza vaccine in patients with Wegener's granulomatosis and showed similar response in the patients to those present in healthy people.

The role ANCA and anti-GBM antibodies in pulmonary-renal syndrome due to Wegener's granulomatosis.

Pulmonary-renal syndrome (PRS) is defined as a diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis. We present a retrospective study of 22 consecutive patients with Wegener's granulomatosis (WG). Logistic regression analysis and a Wilcoxon test were included in the statistics. Survival time death risk were assessed using the Kaplan-Meier estimator and the Cox proportional hazard model. At recognition, the median Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) was 30.0 (23.0-32.5), PO2 on air was 5.8+/-0.5 kPa, creatinine level was 7.2+/-1.4 mg/dl. Fifteen patients were PR3 positive, among them 4 patients were also positive for anti-glomerular basement membrane antibodies (anti-GBM). Renal biopsy was performed in 16 patients. Histological examination reviled segmental necrotizing crescentic GN in 15 patients. Thirteen patients were initially dialysis-dependent, and 7 required ventilatory support. All patients were treated with methylprednisolone and cyclophosphamide (pulses). The patients were followed up for 24+/-8 months. Of the survivors, 55% and 31% were alive after 1 and 2 years. Early recognition and proper treatment may improve outcome in PRS.