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.

Incidence and Clinical Course of Respiratory Viral Coinfections in Children Aged 0-59 Months.

Clinical data available on coinfections are contradictory concerning both the number of viruses involved and the severity of the condition. A total of 114 patients aged 0-59 months with symptoms of respiratory tract infection were enrolled into the study. Nasal and pharyngeal swabs were tested using the PCR method for the following 12 viruses: influenza A, influenza B, respiratory syncytial virus A (RSV A), respiratory syncytial virus B (RSV B), adenovirus, metapneumovirus, coronavirus 229E/NL63 (hCoV229), coronavirus OC43 (hCoVOC43), parainfluenza virus 1 (PIV-1), parainfluenza virus 2 (PIV-2), parainfluenza virus 3 (PIV-3), and rhinovirus A/B. Coinfections were detected in nine (8 %) patients. Five of the coinfections were related to influenza A (H3N2) virus associated with the following other, single or combined, respiratory viruses: influenza B in one case, hCoV229 in two cases, hCoV229, RSV A, and PIV-2 in one case, and PIV-1, PIV-2, RSV A, RSV B, and adenovirus in one case. The other four coinfections were caused by: adenovirus and hCoVOC43, adenovirus, and rhinovirus, RSV A and PIV-1, influenza B, and RSV B. We did not observe any significant differences in the clinical course of infections caused either by a single or multiple viral factors.

Lund-Mackay System for Computed Tomography Evaluation of Paranasal Sinuses in Patients with Granulomatosis and Polyangiitis.

Granulomatosis with polyangiitis (GPA), a disease capable of affecting any organ, most often acts upon the upper respiratory tract. Diagnostic imaging is primarily represented by computed tomography (CT) of paranasal sinuses. The aim of this study was to define the characteristic changes in paranasal CT in patients with GPA and to evaluate diagnostic usefulness of the Lund-Mackey scoring system (L-M System). The study encompassed 43 patients with GPA of the mean age of 47.7 ± 12.8 years who were treated topically with mupirocin. We found that inflammation occurred mainly in the maxillary sinuses (72%). The mean L-M score was 5.8 ± 6.1. The right maxillary sinus had the highest percentage (12.6%) of score hits of 1, i.e., partial opacification and the left ostiomeatal complex had the highest percentage (7.6%) of score of 2, i.e., complete opacification or obstruction. The following changes were the most characteristic for GPA: sinus mucosal thickening, widespread bone damage, and osteogenesis. We conclude that the long-term topical mupirocin treatment of GPA may inhibit nasal bone damage, but also may led to permanent rhinological changes of the rhinosinusitis type. The Lund-Mackey staging system is a useful diagnostic imaging option in GPA patients.

Prevalence of Olfactory Impairment in Granulomatosis with Polyangiitis.

Granulomatosis with Polyangiitis (GPA) is a rare disease of unknown origin. It may damage all organs and systems, even olfactory and taste sense. The aim of the study was to determine the sense of smell in patients with GPA and to identify factors related to disease course, activity, and duration, which may be associated with olfactory dysfunction. The comparison of olfactory function screening scores with Sniffin' Sticks standardized norms showed that 74% of the investigated patients had olfactory dysfunction. The olfactory performance was diminished in all parts of Sniffin' Sticks test: threshold scores 4.4 vs. 7.1 (p = 0.007); odor discrimination 9.0 vs. 11.9 (p = 0.008); and olfactory identification 9.8 vs. 12.2 (p = 0.011) in the GPA patients vs. control subjects, respectively. Scores acquired during all three parts of the test were combined to assess the TDI-score. The median TDI-score in the GPA group (27.5) was significantly lower than that in the control group (32.0) (p = 0.002). Active nasal and paranasal sinus inflammation in GPA leads to olfactory dysfunction, the patients are often unaware of. The dysfunction is permanent and does not abates along with decreasing intensity of the inflammatory process. GPA therapy should include recommendations on nutrition, personal hygiene, and food poisoning prevention.

Stagnating Low Influenza Vaccine Coverage Rates in the Polish Elderly Population in 2008-2013.

Although annual vaccination is the most effective way of preventing the disease and its severe outcomes, influenza vaccine coverage rates have always been at suboptimal levels in Poland. A retrospective analysis was conducted on influenza vaccine coverage rates among patients older than 65 years at local and national levels. Influenza vaccine coverage rates among the elderly in the capital city of Warsaw ranged from 20.5% in 2013 to 31.5% in 2010 and these rates were higher than those reported at the national level (from 7.6% in 2012 to 11.3% in 2009). At a local level the proportion of vaccines given to the elderly compared to all vaccinated individuals varied from 40 to 52% which was comparable to the proportions reported at the national level (37-48.5%). 69% of the elderly were only vaccinated once during the observation period, and only 0.5% of them repeated the vaccination in each subsequent year. The chance of being vaccinated against influenza more than once was statistically higher among women than men (OR 4.9; 95% CI 4.2-5.8). Influenza vaccine coverage rates are low at both local and national levels and ought to be improved in Poland in future.

Antibiotic consumption pattern in the neonatal special care unit before and after implementation of the hospital's antibiotic policy.

Current and detailed knowledge of antibiotic use is essential in order to implement strategies for reducing the overuse of antibiotics. The objective of our study was to determine the effectiveness of the implementation of the hospital antibiotic policy (HAP) by assessing antibiotic consumption in the Special Neonatal Care Unit (SNCU) in Warsaw, Poland, before and after this intervention. Antibiotic use was calculated in daily defined doses (DDDs) per 100 patient-days and DDDs per 100 admissions. The antibiotics were ranked by volume of DDDs and the number of antibiotics, which accounted for 90 % and 100 % of the total volume, respectively: DU90% and DU100% (where DU stands for drug use). Total antibiotic consumption increased slightly after the introduction of the HAP: the total DDDS was 707.87 and 753.12 in 2011 and 2012, while the number of DDDs/100 admissions was 352.17 and 369.12 in 2011 and 2012, respectively. After the introduction of the HAP, an increase in ampicillin and aminoglycoside use was observed, along with a reduction in the DU100% and DU90% rates (15 vs. 9 and 4 vs. 3, respectively). The introduction of the HAP resulted in changes in antibiotic consumption patterns, but the general antibiotic consumption density remained the same.

Subglottic and tracheal stenosis due to Wegener's granulomatosis.

Wegener's granulomatosis (WG) is characterized histologically by necrotizing granulomatous angitis that most commonly involves the upper, lower respiratory tract and kidneys, but may affect any organ system. Otolaryngological manifestations are frequent and diverse but subglottic stenosis and tracheal stenosis are less common. The aim of the study was to assess the clinical features and the response to treatment in WG patients with subglottic or tracheal stenosis. The disease activity at the time of examination was scored in 55 patients with WG (29 females, 26 males) according to clinical, serological, radiological and bronchoscopic findings: subglottic and tracheal stenosis were observed in 9% and 5% of WG patients, respectively. CT scans of the larynx and trachea showed mucosal thickening extended 3-4 cm below the vocal cords in three and the thyroid cartilage in one patient. The degree of narrowing of the axial luminal diameter ranged 50-90%. Mechanical dilation of the stenosis and long-acting local corticosteroids may be of therapeutic benefit, along with conventional immunosuppressive treatment.

Atherosclerotic factors in PR3 pulmonary vasculitis.

Autoimmune disease such as systemic lupus erythematosus or rheumatoid arthritis are connected with higher risk of atherosclerosis and cardiovascular complications and mortality. This results from inflammatory damage to the vessel wall by vasculitis. The aim of the present study was to evaluate whether patients with Wegener's granulomatosis (WG) and pulmonary involvement have an increased prevalence of atherosclerotic disease as characterized traditional risk factors. Twenty one patients with WG in remission and 15 control subject were entered to the study. Traditional risk factor for cardiovascular disease such as hyperglycemia, hypertension, smoking, obesity, and dyslipidemia were assessed. Both systolic and diastolic blood pressure were higher in WG patients (p<0.025). Total cholesterol, LDL and TG levels were markedly elevated in 18 of the 21 in pulmonary WG patients. Compared with controls, plasma levels of hsCRP were raised in WG patients; 3.68 (0.79-9.75) mg/l vs. 0.14 (0.12-0.59) mg/l (p<0.01). We conclude that non-pharmacological and pharmacological treatments of traditional risk factors are crucial to prevent cardiovascular disease in WG patients and thus should be part of therapy to control WG activity and damage caused by it.

Clinical manifestations of influenza caused by A/H1N1v virus among children and teenagers consulted in general practice.

BACKGROUND: Children and young adults are more susceptible to pandemic A/H1N1v infection than older people. There are some publications concerning the course of the pandemic influenza among pediatric population but mostly from hospital or from emergency units. There are very few observations of the course of pandemic influenza from primary care settings. OBJECTIVE: The aim of the study was to describe clinical manifestations of influenza caused by a pandemic strain A/H1N1v among children and teenagers younger than 14 years who were observed, diagnosed, and treated in general practice. MATERIAL AND METHODS: The observations were conducted among patients with symptoms of an acute respiratory tract infection in an urban area of Warsaw, Poland in November 2009. The inclusion criteria for performing a rapid influenza diagnostic test (RIDT) were established using the CDC definition of 'influenza-like illness' (ILI): fever >38.7°C plus cough and/or sore throat in the absence of another known cause of illness. In patients who met ILI criteria, nasopharyngeal swabs were taken for RIDT and RT-PCR. - RESULTS: 433 patients were consulted by a general practitioner and reported symptoms of an acute respiratory tract infection, 128 (30%) of them met inclusion criteria for ILI and were tested with RIDT: 31 children younger than 14 years and 97 adults. All 31 children suspected of ILI also were tested by RT-PCR. 20 children had a positive result of the rapid influenza test. For all children tested negative, RT-PCR was also negative, and out of 20 children with the presumptive diagnosis of influenza established after rapid influenza test, the diagnosis was confirmed by RT-PCR in 18; their median age was 6.6 years and ranged from13 months to 14 years. The most common symptoms of influenza A/H1N1v were: high fever (>39°C) - 96% of patients, dry cough - 86% of patients, malaise - 78% of patients, headache - 66% of patients, and diarrhea or vomiting - 28% of patients. Two children received treatment with oseltamivir (one boy with congenital heart defect and Down's syndrome and another with severe bronchial asthma). The duration of symptoms ranged from 1 to 13 days (mean of 6.6 days). No patients required hospitalization either due to primary influenza infection or secondary complications. CONCLUSIONS: The course of influenza caused by virus A/H1N1v in children younger than 14 years observed in a primary care setting was mild and self-limited without the necessity of antiviral treatment in most cases. A rapid influenza diagnostic test is helpful in diagnosing pandemic influenza.

Influenza vaccine coverage among children under the age of 5 years in Poland during 2004-2008.

INTRODUCTION: Influenza is a considerable health problem all over the world. The most important group for influenza vaccination are children: the highest attack rate during community out-breaks of influenza can be found among school-aged children or their family members; children bear a considerable risk for complications due to influenza, leading to an increased need for healthcare resources (including hospitalization). The high level of vaccine coverage among school children could provide protection against influenza among households and could reduce mortality rates among older individuals. OBJECTIVE: The aim of this study was to estimate the influenza vaccine coverage among children younger than 5 years and to find any trends in influenza vaccine coverage in 2004-2008 in Poland. MATERIAL AND METHODS: Official data (number of administrated vaccines and the age of vaccinated individuals) collected by the National Institute of Hygiene, the National Institute of Public Health, and the Central Statistical Office in Poland were analyzed. This data are reported by physicians and collected from reports prepared annually by the Sanitary-Epidemiological Stations at a local level. The vaccine coverage rate was calculated as a percentage of vaccinated individuals among all children under the age of 5 years. RESULTS: The influenza vaccine coverage among children younger than 5 years varied from 1% (2007 and 2008) to 1.9% (2005). The proportion of vaccinated children aged less than 5 compared with the total number of flu shots administrated irrespective of age also varied from 1.4% (2007) to 2% (2005). CONCLUSIONS: The influenza vaccination coverage among Polish children aged less than 5 years is low and has persisted at the same level. More educational activities directed both to patients (parents) and healthcare workers would be needed to improve a general knowledge about influenza vaccination benefits among young children.

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.