Aspirin desensitization in patients with aspirin-induced and aspirin-tolerant asthma: a double-blind study.

BACKGROUND: Numerous open trials have demonstrated the beneficial clinical effects of aspirin desensitization (AD) in patients with aspirin-induced asthma (AIA). These beneficial effects might be attributable to aspirin's potent anti-inflammatory properties, but that supposition requires further corroboration. OBJECTIVE: We sought to compare the clinical and biochemical responses to chronic oral AD in 20 patients with AIA and 14 patients with aspirin-tolerant asthma (ATA). All of the patients had chronic rhinosinusitis and nasal polyposis, and these responses were investigated in a pilot, double-blind, placebo-controlled study. METHODS: Twelve patients with AIA and 6 patients with ATA were randomly assigned to receive 624 mg of aspirin, and 8 patients with AIA and 8 patients with ATA received placebo. Both aspirin and placebo were administered once daily for 6 months. Nasal symptoms, Sino-Nasal Outcome Test (SNOT20) scores, peak nasal inspiratory flows, Asthma Control Questionnaire scores, spirometric parameters, peak expiratory flows, blood eosinophilia, and corticosteroid doses were assessed on a monthly basis. Levels of urinary leukotriene E4 and the stable plasma prostaglandin (PG) D2 metabolite 9α,11ß-PGF2 were evaluated at baseline and after 1, 3, 5, and 6 months. RESULTS: Only the patients with AIA subjected to AD reported improvements in smell and reductions in sneezing and nasal blockade. The SNOT20 and Asthma Control Questionnaire scores of these patients decreased, and their peak nasal inspiratory flows increased. The dosages of inhaled corticosteroids were reduced. There were no changes in leukotriene E(4) or 9α,11ß-PGF(2) levels after AD. CONCLUSION: The clinically beneficial effects of AD on nasal and bronchial symptoms occurred only in the patients with AIA.

Certain subphenotypes of aspirin-exacerbated respiratory disease distinguished by latent class analysis.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is recognized as a distinct asthma phenotype. It usually has a severe course accompanied by chronic hyperplastic eosinophilic sinusitis with nasal polyps, blood eosinophilia, and increased concentrations of urinary leukotriene E4 (LTE4). More insightful analysis of individual patients shows this group to be nonhomogeneous. OBJECTIVE: We sought to identify any likely subphenotypes in a cohort of patients with AERD through the application of latent class analysis (LCA). METHODS: Clinical data from 201 patients with AERD (134 women) were collected from questionnaires. Standard spirometry, atopy traits, blood eosinophilia, and urinary LTE4 concentrations were evaluated. LCA was applied to identify possible AERD subphenotypes. RESULTS: Four classes (subphenotypes) within the AERD phenotype were identified as follows: class 1, asthma with a moderate course, intensive upper airway symptoms, and blood eosinophilia (18.9% of patients); class 2, asthma with a mild course, relatively well controlled, and with low health care use (34.8% of patients); class 3, asthma with a severe course, poorly controlled, and with severe exacerbations and airway obstruction (41.3% of patients); and class 4, poorly controlled asthma with frequent and severe exacerbations in female subjects (5.0% of patients). Atopic status did not affect class membership. Patients with particularly intensive upper airway symptoms had the highest levels of blood eosinophilia and the highest concentrations of urinary LTE4. CONCLUSIONS: LCA revealed unique AERD subphenotypes, thus corroborating the heterogeneity of this population. Such discrimination might facilitate more individualized treatment in difficult-to-treat patients.

Exercise training in intermittent claudication: effects on antioxidant genes, inflammatory mediators and proangiogenic progenitor cells.

Exercise training remains a therapy of choice in intermittent claudication (IC). However, too exhaustive exercise may cause ischaemic injury and inflammatory response. We tested the impact of three-month treadmill training and single treadmill exercise on antioxidant gene expressions, cytokine concentrations and number of marrow-derived proangiogenic progenitor cells (PPC) in the blood of IC patients. Blood samples of 12 patients were collected before and after training, before and 1, 3 and 6 hours after the single exercise. PPCs were analysed with flow cytometry, cytokine concentrations were checked with Milliplex MAP, while expression of mRNAs and miRNAs was evaluated with qRT-PCR. Treadmill training improved pain-free walking time (from 144 ± 44 seconds [s] to 311 ± 134 s, p=0.02) and maximum walking time (from 578 ± 293 s to 859 ± 423 s, p=0.01) in IC patients. Before, but not after training, the single treadmill exercise increased the number of circulating CD45dimCD34+CD133-KDR+ PPCs (p=0.048), decreased expression of HMOX1 (p=0.04) in circulating leukocytes, reduced tumour necrosis factor-α (p=0.03) and tended to elevate myeloperoxidase (p=0.06) concentrations in plasma. In contrast, total plasminogen activator inhibitor-1 was decreased by single exercise only after, but not before training (p=0.02). Both before and after training the single exercise decreased monocyte chemoattractant protein (MCP)-1 (p=0.006 and p=0.03) concentration and increased SOD1 (p=0.001 and p=0.01) expression. Patients after training had also less interleukin-6 (p=0.03), but more MCP-1 (p=0.04) in the blood. In conclusion, treadmill training improves walking performance of IC patients, attenuates the single exercise-induced changes in gene expressions or PPC mobilisation, but may also lead to higher production of some proinflammatory cytokines.

Increased production of IL-5 and dominant Th2-type response in airways of Churg-Strauss syndrome patients.

OBJECTIVE: Churg-Strauss syndrome (CSS) is a rare systemic vasculitis associated with eosinophilia and asthma. We assessed the local immune response in airways of CSS patients with different activity of the disease. METHODS: Concentration of IL-5, CCL17, CCL22 and CCL26 (ELISA) together with cell expression of T-helper-related genes (real-time PCR array) were measured in bronchoalveolar lavage fluid (BALF) sampled from 11 patients with active CSS, 11 patients with CSS in remission and 9 control subjects with bronchial asthma. RESULTS: In active CSS, both BALF and blood eosinophil counts were increased (P<0.01). BALF cells in active disease were characterized by an increased expression of Th2 and regulatory-type transcripts: STAT6, STAT3, GATA3, IL4, IL5 and IL10 as compared with asthmatics, and STAT5A, CCR4, FOXP3, IL4, IL5 and IL10 when compared with inactive CSS. There was significant increase in BALF concentration of IL-5 and CCL26 in exacerbation of CSS. CCR4-active chemokines were detected more frequently in active disease. We found a strong positive correlation between clinical parameters of disease activity (BVAS, eosinophilia) and expression of IL4, IL5, IL10 and STAT5A. CONCLUSION: These results indicate that as compared with asthma, active-CSS patients have much stronger local Th2 response in the airways. Airway cells may contribute to lung eosinophilia in CSS by producing IL-5 and eosinophil active chemokines.

Increase in plasma sCD23 levels precedes immunoglobulin E elevation after coronary artery bypass graft surgery.

INTRODUCTION: Recent reports have confirmed an increase in plasma immunoglobulin E (IgE), which had been previously observed in clinical situations associated with tissue injury. Studies on the regulation of IgE levels have pointed to the role of low-affinity IgE receptor, i.e., sFcεRII (soluble CD23 [sCD23]). OBJECTIVES: The aim of the study was to assess the changes in the levels of this receptor in response to surgical injury during coronary artery bypass grafting. PATIENTS AND METHODS: The study group consisted of 33 patients (28 men and 5 women, aged 45-75 years). Blood samples were obtained from all patients before surgery and 24, 48, 72, and 120 hours after the surgery. The expression of FcεRII on B cells was measured using flow cytometry and plasma levels of sCD23 were determined by an enzyme-linked immunosorbent assay. RESULTS: We observed a significant increase in the total number of leukocytes and a significant decrease in the total number of lymphocytes with a simultaneous increase in the proportion of B cells (P <0.001). At the same time, the percentage of CD23-positive B cells (CD19/23+) decreased significantly (P <0.001) at 24 hours after surgery and remained low over the period of 72 hours. The plasma levels of sCD23 increased significantly (P <0.05) at 24 hours after surgery and remained elevated until the end of follow-up. All the above changes in the immune status preceded an increase in plasma IgE levels (P <0.001), which reached peak values on the fifth day after surgery (120 h). CONCLUSIONS: Surgical procedures are associated with a transient increase in plasma IgE levels, which is preceded by an increase in the level of sCD23 and a simultaneous decrease in the expression of CD23 on B cells. FcεRII (CD23) and sFcεRII (sCD23) may be involved in the regulation of IgE levels after trauma.

Both Th2 and Th17 responses are involved in the pathogenesis of Churg-Strauss syndrome.

OBJECTIVES: Churg-Strauss syndrome (CSS) is a rare systemic vasculitis associated with eosinophilia and granuloma formation. The contribution of individual T-helper cell lineages in pathogenesis of CSS is unknown. We hypothesised that in CSS an imbalance of major effector T-cell subpopulations takes place, and is further influenced by the mode of treatment. METHODS: We investigated the immunophenotype, cytokine production and transcriptome profile in peripheral blood lymphocytes (PBL) from 19 patients with stable CSS (10 were treated with glucocorticoids alone (CSS/GC), 9 with steroids and other immunosuppressive drugs (CSS/IS)), and 13 healthy controls. Furthermore, serum IL-5 and CCR4-active chemokines (CCL17, CCL22) were measured in six patients with active disease and upon remission. RESULTS: All CSS patients had decreased percentage of FoxP3+ regulatory T cells. In the CSS/GC group we found an increase in the Th17/Treg ratio and up-regulation of both Th2 and Th17 markers as evidenced by (1) over expression of Th2-related genes (GATA3, STAT6) in PBL, (2) elevated concentrations of serum IL-5 and CCL17, and (3) a concomitant increase in the number of Th17 cells, and secretion of IL-17A by stimulated PBL. The level of CCR4-active chemokines was increased in active-CSS, and correlated with blood eosinophilia. The combined treatment with steroids and other immunosuppressive drugs was associated with a significant decrease in both Th2-related chemokines and the number of Th17 cells. CONCLUSIONS: Our results indicate that both Th2 and Th17 lineages are involved in the pathogenesis of CSS, while CCR4-active chemokines contribute to eosinophilia in the active disease. These phenomena are down regulated by immunosuppressive therapy.

Efficacy of physical therapy methods in airway clearance in patients with chronic obstructive pulmonary disease: a critical review.

Multiplicity and variety of chest physical therapy (CPT) methods for increasing bronchial clearance in patients with chronic obstructive pulmonary disease (COPD) require an assessment of validity and reliability of the available clinical evidence. The aim of the review was to evaluate publications on CPT in COPD patients and to establish the basis (objective criteria) on which given methods and techniques are recommended or refuted. Systematic reviews, narrative reviews, and clinical practice guidelines, published in English between January 1, 2000 and July 1, 2010, were identified from the PubMed/MEDLINE and Cochrane (DARE, CRD, The Cochrane Airways Review Group Register) databases. The PEDro and SIGN scales were used to assess the quality and grade of recommendations for selected papers. Generally, the papers that we identified were based on small studies, limited to short-term outcomes, mostly using crossover designs, and rarely including sham therapy. Recommendations from clinical guidelines were mainly grade C or D. Health-related quality-of-life analyses, including working and exercise capacity, are lacking. The evidence from the studies in patients with cystic fibrosis cannot be directly extrapolated to COPD subjects. Despite the lack of convincing evidence, clinical practice supports the value of CPT in COPD. However, when making a clinical decision, potential side effects should be considered.

Eoxins: a new inflammatory pathway in childhood asthma.

BACKGROUND: Increased levels of leukotrienes (LTs) in exhaled breath condensate (EBC) are associated with asthma and bronchial hyperresponsiveness (BHR), whereas eicosanoids generated through the 15-lipoxygenase (LO) pathway (15-hydroxyeicosatetraenoic acid [HETE] and eoxins) have been less studied. OBJECTIVE: We investigated whether metabolites of the 5- and 15-LO pathways in EBC are associated with childhood asthma, asthma severity, and clinical parameters. METHODS: The present study included 131 school-aged children (27 children with problematic severe asthma, 80 children with mild-to-moderate asthma, and 24 healthy children) from the Severe Asthma Recognized in Childhood study and 19 children with other nonasthmatic chronic lung diseases. Clinical work-up included spirometry, fractional exhaled nitric oxide measurements, skin prick testing, and methacholine challenge. Eicosanoids were analyzed in EBC by using mass spectrometry and are reported as concentrations (in picograms per milliliter) and eicosanoid/palmitic acid (PA) ratios. RESULTS: Eoxin C4/PA, eoxin D4/PA, eoxin E4/PA, 15-HETE/PA, and LTC4/PA ratios were significantly increased in asthmatic versus healthy children. Eoxin D4/PA and LTE4/PA ratios were also significantly higher in children with BHR. A nonsignificant trend was observed toward higher eoxin/PA ratios with increasing asthma severity. In contrast to asthma, children with chronic lung disease had the highest 15-HETE/PA, LTC4/PA, LTE4/PA, and LTB4/PA ratios. CONCLUSION: The results point to increased activity of the 15-LO inflammatory pathway in childhood asthma. Mass spectrometric analyses of EBC demonstrate that increased eoxin levels not only accompany the increased 5-LO product LTC4 but are also associated with BHR. These markers might represent a new therapeutic target for asthma treatment.

Aspirin-induced asthma: a tribute to John Vane as a source of inspiration.

Aspirin-induced asthma is a distinct clinical syndrome consisting of inflammation, characterized by chronic eosinophilic rhinosinusitis with asthma and often nasal polyposis. Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) exacerbate asthma, resulting in violent attacks. This is the hallmark of the clinical syndrome as explained by the cyclooxygenase theory. This theory, which is now generally accepted, states that asthma attacks precipitated by aspirin and other NSAIDs have no allergic background; instead, they occur due to the inhibition of cyclooxygenase-1 in sensitive patients. This paper describes how the discoveries of John Vane inspired the authors of the cyclooxygenase theory and led to further insight into the biology of eicosanoid metabolism in this relatively common type of asthma.

The influence of simvastatin on selected inflammatory markers in patients with chronic obstructive pulmonary disease.

INTRODUCTION: There is growing evidence that chronic obstructive pulmonary disease (COPD) is a risk factor for coronary heart disease. Simvastatin is a hypolipemic drug with proven efficacy in the prevention of cardiovascular diseases. Observational studies showed that statins may be useful in the reduction of mortality from COPD. Experimental studies on animals showed anti-inflammatory effects of statins on the lung tissue. OBJECTIVES: The aim of this study was to evaluate the influence of simvastatin on inflammatory markers in patients with COPD. PATIENTS AND METHODS: Fifty-six patients (aged 44-80 years) with stable COPD (a mean forced expiratory volume in 1 second [FEV1] 55%), were randomly assigned (1:1) to receive simvastatin 40 mg/day or to receive no statin treatment. Blood samples were collected before, 2 weeks, and 3 months after statin administration. The levels of fibrinogen, C-reactive protein (CRP), tumor necrosis factor-alpha, interleukin 6 (IL-6), and matrix metalloproteinase-9 were measured. RESULTS: The groups did not differ significantly in terms of demographic data, clinical symptoms, pharmacological treatment, spirometry, and lipid profile at baseline. Among comorbidities only arterial hypertension was more frequent in the statin group (32.1% vs. 17.9%, P = 0.03). After 2 weeks as well as 3 months of simvastatin treatment, no significant reduction of any measured inflammatory markers was observed. There was a nonsignificant reduction of CRP and IL-6 in the subgroup with FEV1 >50% during simvastatin treatment. There was a decrease in total cholesterol (from 5.7 to 4.7 mmol/l, P = 0.0018) and low-density lipoprotein cholesterol (from 3.46 to 2.47 mmol/l, P = 0.000037) in the statin group. CONCLUSIONS: In COPD patients, a 3-month treatment with simvastatin does not reduce circulating inflammatory markers.

Intrinsic pathway of apoptosis in peripheral blood eosinophils of Churg-Strauss syndrome.

OBJECTIVES: Churg-Strauss syndrome (CSS) is a rare necrotizing vasculitis associated with asthma, blood and tissue eosinophilia and granuloma formation. We wondered whether eosinophil accumulation in CSS results from the defect of intrinsic apoptosis pathway in blood eosinophils, leading to their prolonged survival. METHODS: We analysed immunophenotype (flow cytometry), expression of apoptosis-related genes (real-time PCR) and spontaneous apoptosis in blood eosinophils isolated from nine patients in exacerbation (active CSS), seven patients in remission (inactive CSS) and 14 matched healthy subjects. Serum IL-5 levels were also measured. RESULTS: In active CSS, blood eosinophils were characterized by small (<2-fold) decrease in expression of a few genes, primarily proapoptotic (e.g. BCL2L13, CASP2, CARD4) or involved in regulation of NF-kappaB (IKBKB, REL), but they did not differ in the rate of spontaneous apoptosis, when compared with other groups. Only selected genes were positively (BNIPL, PYCARD, CASP8, CRADD, BCAP31), or negatively (IKBKE) correlated with disease activity. In active CSS, eosinophils expressed activation markers (CD69, CD25), especially in subjects with most severe disease and elevated serum IL-5. CONCLUSIONS: High susceptibility of peripheral blood eosinophils to spontaneous apoptosis in vitro, and minor changes in expression of apoptotic-related genes in transcriptome analysis, do not support the hypothesis on intrinsic defect in apoptosis, as the cause of eosinophil accumulation in CSS.

Genetic associations of variants of the high affinity receptor for immunoglobulin E in Wegener's granulomatosis.

Immunoglobulin E (IgE) and the high affinity IgE receptor (FcepsilonRI) have been suggested to contribute to the pathogenesis of autoimmune disorders. Their role in Wegener's granulomatosis (WG) are, however, poorly recognized. We sought a genetic association between laboratory markers for the disease, i.e. anti-proteinase 3 antibodies (anti-PR3), anti-myeloperoxidase antibodies, anti-cyclic citrullinated peptide antibodies, C-reactive protein (CRP), C3c and C4 complement components, and total serum IgE levels in WG subjects with common genetic variants of FcepsilonRI subunits. Anti-PR3 and CRP and serum IgE levels showed significant associations, while complement components tended to be associated, with -18483A > C and/or -344C > T FCER1A (FcepsilonRI alpha-subunit gene) polymorphisms. Moreover, a correlation between -109T > C FCER1B (FcepsilonRI beta-subunit gene) genotypes and serum IgE was observed. Both WG specific auto-antibodies and other blood inflammatory markers displayed correlations with serum total IgE levels and genetic variants of the high affinity receptor for this immunoglobulin. This observation suggests a functional relantionship of FcepsilonRI in the regulation of autoimmune response observed in WG.

The use of endobronchial ultrasonography in assessment of bronchial wall remodeling in patients with asthma.

BACKGROUND: Endobronchial ultrasound (EBUS) is a new technique that enables the assessment of bronchial wall layers. The aim of the study was to verify the utility of EBUS for the assessment of bronchial wall remodeling in patients with asthma. METHODS: In 35 patients with asthma and 23 control subjects, high-resolution CT (HRCT) scanning and EBUS were used to measure bronchial wall thickness in the 10th segment of the right lung. With a radial 20-MHz probe, EBUS identified the 5-laminar structure of the bronchial wall. Layer 1 (L(1)) and layer 2 (L(2)) were analyzed separately, and layers 3 through 5 (L(3-5)), which corresponded to cartilage, were analyzed jointly. Digitalized EBUS images were used for the quantitative assessment of bronchial wall thickness and the wall area (WA) of the layers. Finally, bronchial biopsy specimens were taken for measuring the thickness of the reticular basement membrane (RBM). The thickness and WA of the bronchial wall layers, which were assessed using EBUS, were correlated with FEV(1) and RBM. RESULTS: There was no significant difference in the measurements of total bronchial wall thickness using EBUS and HRCT scanning. The thickness and WA of the bronchial wall and its layers were significantly greater in patients with asthma than in the control subjects. A negative correlation among the thicknesses of L(1), L(2), and L(3-5) and FEV(1), and a positive correlation with RBM were observed only in the patients with asthma. CONCLUSIONS: EBUS allows precise measurement of the thickness and WA of bronchial wall layers. The correlation of these parameters with asthma severity suggests implementation of EBUS in the assessment of bronchial wall remodeling in patients with asthma.

Clinical course and urinary eicosanoids in patients with aspirin-induced urticaria followed up for 4 years.

BACKGROUND: Little is known about the course of aspirin-induced urticaria. A special regulatory role of cysteinyl leukotrienes and prostaglandin D(2) (PGD(2)) has been postulated. OBJECTIVE: We performed a long-term observation on clinical course, aspirin sensitivity, and urinary eicosanoids in patients with aspirin-induced urticaria. METHODS: For 4 years, we followed up 22 patients with chronic idiopathic urticaria and aspirin hypersensitivity who restrained from the use of aspirin and other COX-1 inhibitors. Aspirin challenges were performed in 2002 (all results were positive) and repeated in 2006. Levels of urinary leukotriene E(4) (LTE(4)) and the main PGD(2) metabolite, 9 alpha 11 beta PGF(2), were measured at the same time points. RESULTS: During the follow-up period, the severity of urticaria has decreased. In 14 of 22 patients, the results of aspirin challenge remained positive. In 2002, these 14 patients responded to aspirin with a significant increase in urinary LTE(4) and 9 alpha 11 beta PGF(2) levels. When studied 4 years later, they showed a similar response of 9 alpha 11 beta PGF(2) (P = .047) and a tendency toward an increase in LTE(4) level (P = .057). There was a correlation between the urinary LTE(4) concentration after aspirin challenge and the intensity of skin eruptions. The dose of aspirin had no effect on the magnitude of response of both LTE(4) and the PGD(2) metabolite. In the remaining 8 patients, negative aspirin challenge results were not associated with changes in the urinary eicosanoids studied. CONCLUSIONS: Aspirin hypersensitivity manifesting as urticaria/angioedema remains present after 4 years in about two thirds of patients. Aspirin-precipitated skin reactions associate with increased excretion of LTE(4) and PGD(2).

[Congestive cardiomyopathy and left intraventricular thrombus as a manifestation of Churg-Strauss syndrome]. / Kardiomiopatia zastoinowa i skrzeplina w lewej komorze jako manifestacje zespolu Churga i Strauss.

A case of a 38-year-old female with symptomatic Churg-Strauss syndrome and congestive cardiomyopathy, complicated by cardiac arrest and left ventricular thrombus formation, is presented. Prompt institution of low molecular weight heparin and steroids resulted in rapid thrombus lysis and improvement of systolic left ventricular function.

Prevalence of COPD and tobacco smoking in Malopolska region--results from the BOLD study in Poland.

INTRODUCTION: There is a paucity of population-based data on chronic obstructive pulmonary disease (COPD) prevalence in Poland. To address this problem we participated in the Burden of Obstructive Lung Disease (BOLD) Initiative which was developed to provide standardized methods for estimating the prevalence of COPD and its risk factors. OBJECTIVES: The study aimed to assess the prevalence of COPD and some of its risk factors in adults aged 40 years and older in the Malopolska region in southern Poland. PATIENTS AND METHODS: Region--representative sample was drawn, basing on the current census data. Detailed BOLD questionnaires as well as pre- and post-bronchodilator spirometry were applied to eligible individuals. RESULTS: Six hundred and three subjects provided questionnaire and spirometry data; of those 526 provided spirometry data of appropriate quality and were included in the final analysis. Estimated population prevalence of COPD was 22.1%, whereas 10.9% had COPD in GOLD Stage > or = 2. COPD was far more common in men and its prevalence increased with age and exposure to tobacco smoke, and was inversely related to education level. The prevalence of current tobacco smoking was 28% (34% and 22% in men and women, respectively). Seventy-nine percent of men and 42% of women were ever-smokers. Twenty-nine percent of never smoking individuals were passively exposed to tobacco smoke in their households. CONCLUSIONS: Our results confirm the high prevalence of COPD in the studied region of Poland and emphasize the need to increase efforts to improve COPD awareness and limit tobacco smoking habit.

Long-term effects of thoracic sympathectomy on microcirculation in the hands of patients with primary Raynaud disease.

OBJECTIVE: Videothoracoscopic sympathecomy is a widely used treatment modality in patients with severe Raynaud disease, but the reported late results are less than favorable. There have been no direct studies of the long-term effect of sympathectomy on microcirculation in the hands of these patients. METHODS: In 25 patients with Raynaud disease treated with videothoracoscopic Th2-Th4 sympathectomy, we performed basal laser-Doppler flowmetry and measured the maximal refilling time after 1-minute occlusion measurements preoperatively and at 1 week, 6 months, and 1, 2, 3, and 5 years after the sympathectomy. The results were compared with the same measurements obtained in the group of 50 healthy individuals. RESULTS: The patients' symptom severity was assessed by using the visual analogue scale. The basal capillary flow and the maximal refilling time improved after the sympathectomy to a level not different from that seen in the healthy population, and the effect was maintained during the 5-year follow-up period. The patients' symptom severity scores diminished to zero in the early postoperative period and increased to 28% of their initial value 5 years after the operation. CONCLUSIONS: The videothoracoscopic Th2-Th4 sympathectomy produces excellent and long-lasting improvement of microcirculation function in patients with Raynaud disease. The mild return of symptoms might be due to factors other than the capillary blood flow alterations.

Assessment of airway caliber in quantitative videobronchoscopy.

BACKGROUND: Quantitative assessment of airway caliber is generally confined to indirect methods. Fiberoptic bronchoscopy provides a direct view of the airways, but measurement of the internal size of bronchi in a standard examination is not possible. Using a special image analysis program, we developed a method allowing quantitative assessment of airway caliber by means of videobronchoscopic (VB) examination. OBJECTIVES: The purpose of the study was toshow that quantitative videobronchoscopy (VB coupled with a computer image analysis) allows direct and accurate measurement of the bronchi diameter. METHODS: To test our hypothesis, we measured the same areas of a bronchial tree in CT and in VB in 40 patients with diagnostic indications for both the procedures. RESULTS: We measured the diameters of 149 bronchi. The mean value of the difference between VB and CT measurements was equal to -0.071 mm and was not significantly different from 0 (p = 0.086). There was no obvious relation between the difference and the mean (r = 0.026, p = 0.745). The Bland Altman limits of agreement were L = -1.071 mm and U = 0.929 mm. We also assessed the bronchial diameter after endobronchial challenge and in patients with tracheobronchomalacia to show the application of this method for dynamic measurements. CONCLUSIONS: Quantitative videobronchoscopy allows the accurate and direct measurement of an airway caliber. It may be useful in clinical setting to quantify changes in a bronchial caliber (endobronchial masses, tracheobronchomalacia). Dynamic visualization of changes in airways may be useful in research, especially to explore the mechanics of airway narrowing.

The broken balance in aspirin hypersensitivity.

Aspirin was introduced into medicine over a century ago and has become the most popular drug in the world. Although the first hypersensitivity reaction was described soon after aspirin had been marketed, only recently a phenomenon of cysteinyl leukotriene overproduction brought new insights on a balance between pro- and anti-inflammatory mediators derived from arachidonic acid. We describe the most common clinical presentations of aspirin hypersensitivity, i.e. aspirin-induced asthma, rhinosinusitis and aspirin-induced urticaria. We also present their biochemical background. Despite relatively high incidence of these reactions, aspirin hypersensitivity remains underdiagnosed worldwide. Acute reactions of aspirin hypersensitivity are elicited via cyclooxygenase inhibition by non-steroid anti-inflammatory drugs. Coxibs, selective inhibitors of cyclooxygenase-2 isoenzyme, do not precipitate symptoms in susceptible patients. Though hypersensitivity correlates with cyclooxygenase-1 inhibition, diminished tissue expression was described only for cyclooxygenase-2. Aspirin-induced asthma and aspirin-induced urticaria, in a substantial part of the patients, are driven by a release of mediators from activated mast cells. These cells in physiological conditions are under inhibitory control of prostaglandin E2. The origin of aspirin hypersensitivity remains unknown, but accumulating data from genetic studies strongly suggest that environmental factor, possibly a common viral infection, can trigger the disease in susceptible subjects.