Proportion Of Eosinophils Research Articles

Competitive swimmers with allergic asthma show a mixed type of airway inflammation: Fig. 1—

To the Editors: Elite swimmers are at increased risk of asthma 1. This has been attributed to airway inflammation and increased airway responsiveness induced by high-intensity long-term exercise and repeated exposure to the chlorine-rich atmosphere in swimming pools during training and competition 2, 3. Recently, increased levels of leukotriene (LT)B4 in exhaled breath condensate and normal exhaled nitric oxide fraction ( F eNO) levels have been reported in five elite swimmers, suggesting possible underlying neutrophilic airway inflammation 4. Previous analysis of induced sputum in nonasthmatic elite swimmers showed increased proportion of eosinophils and neutrophils compared with healthy controls 3. We aimed to characterise the airway inflammation in competitive asthmatic swimmers. Athletes from the FC Porto main swimming team and 20 nonathlete asthmatics were recruited; participants gave informed consent. Subjects were classified by their asthma and training status as asthmatic swimmers (n = 6, two female, aged 17±2 yrs, competing 8±3 yrs, training 16±4 h·week−1), asthmatics (n = 20, eight female, aged 14±3 yrs) and swimmers (n = 20, six female, aged 17±2 yrs, competing 8±3 yrs, training 17±3 h·week−1). All asthmatics and nine (45%) of the swimmers were atopic according …

Continued inhalation of lidocaine suppresses antigen-induced airway hyperreactivity and airway inflammation in ovalbumin-sensitized guinea pigs

It is unclear whether inhaled lidocaine is effective against airway hyperreactivity and inflammation in asthma. The aim of this study was to investigate the effects of inhaled lidocaine on airway hyperreactivity and inflammation. Airway reactivity to inhaled histamine, cellular composition of bronchoalveolar lavage (BAL) fluid, plasma substance P (SP), and isolated lung tissue were evaluated in ovalbumin (OVA)-sensitized guinea pigs 7 days after OVA challenge. The effects of inhaled lidocaine on this model were also evaluated. Treatment with lidocaine was administered in two fashions: as single inhalation or inhalation bid for 7 consecutive days, for comparison with a saline-inhaled control group. Airway hyperreactivity to histamine, increase in number of total cells and increased proportion of eosinophils in BAL fluid, and marked eosinophil infiltration in airway walls were noted even 7 days after OVA challenge in the control group. Plasma SP level was also significantly increased. Although treatment with single lidocaine inhalation did not affect airway hyperreactivity, continued inhalation (bid for 7 days) attenuated airway hyperreactivity. Continued, but not single, inhalation of lidocaine also suppressed infiltration of eosinophils in BAL fluid and in airway walls. In addition, plasma SP levels were significantly reduced by continued but not by single inhalation. It appears possible that lidocaine when inhaled suppresses eosinophilic inflammation of the airway and SP-induced neurogenic inflammation, leading to alleviation of airway hyperreactivity.

Exhaled Nitric Oxide Levels After Specific Inahalatory Challenge Test in Subjects with Diagnosed Occupational Asthma

Measuring exhaled nitric oxide (eNO) is a useful method for the assessment of bronchial inflammation in asthmatic subjects. The aim of the study was to evaluate the changes in eNO level in the subjects with suspected occupational asthma (OA) after a specific inhalation test (SIT) with occupational agents. Forty two patients, including 17 farmers, 15 bakers and 10 health care workers had a physical examination, skin prick tests with common and occupational allergens, total serum IgE level, specific anti-allergen IgE determinations, spirometry and SIT. Also, morphological changes in induced sputum (ISP) and nasal lavage fluid (NLF) were analysed and eNO measurements were performed. SIT revealed a significant increase in the proportion of eosinophils in NLF and in ISP in the cases with diagnosed OA. Moreover, these cases showed significantly increased eNO levels only 24 h after SIT, compared to the measurements before SIT. We also found a significant correlation between eNO level at 24 h after SIT and the percentage of eosinophils in NLF before, and 4 and 24 h after SIT, as well as in ISP before and 24 h after SIT in all subjects with diagnosed OA. The findings may confirm the usefulness of exhaled nitric oxide measurements for diagnosing OA.

Occupational Asthma Due to Manganese Exposure: A Case Report

Manganese belongs to a group of agents called "transitional metals" that are known to induce occupational asthma. However, well-documented cases of manganese-induced asthma have been lacking thus far. We have discussed a case of a 42-year-old non-smoking welder with work-related dyspnea. A number of clinical procedures were performed including clinical examination, routine laboratory tests, total serum IgE, skin prick tests to common aeroallergens and manganese nitrate, resting spirometry test, histamine challenge, and a single-blind, placebo-controlled specific inhalation challenge with 0.1% manganese chloride solution. Clinical findings and laboratory test results remained normal but a significant bronchial hyperreactivity was found. During the specific inhalation challenge, dyspnea and a significant decrease in forced expiratory volume (FEV1) were observed. An increased proportion of eosinophils and basophils in induced sputum could also be noted at 4 and 24 h after the challenge. The argument for recognizing the condition as occupational asthma was a positive clinical response to the specific challenge test as well as the morphological changes found in induced sputum. To our knowledge, this is the first well-documented case of manganese-induced occupational asthma.

Cellular Analysis of Cutaneous Leishmaniasis Lymphadenopathy: Insights into the Early Phases of Human Disease

Lymphadenopathy is an early clinical sign in cutaneous leishmaniasis (CL), caused by Viannia parasites, and may help to understand the initial host response to these species of Leishmania. We report on characteristics of cells obtained from lymph nodes from cutaneous leishmaniasis patients with lymphadenopathy without ulceration (early phase, N = 21) or lymphadenopathy and ulceration (late phase, N = 29). Early-phase patients exhibited a higher proportion of neutrophils, eosinophils, and CD8+ T cells. Conversely, CD19+ B lymphocytes and plasma cells were more frequently observed in late-phase patients. The signal for IL-10 was significantly higher in late-phase patients; signals for IFN-gamma or IL-4 were similar in both groups. These data reinforce observations of an initial mixed Th1-Th2 profile as well as the early role of the CD8 T cell in cutaneous leishmaniasis. Additionally, there is a chronologic relationship between ulcer development and B-cell increase. IL-10 also increases at a late stage and may be important in limiting tissue damage.

Relationship Between Eosinophilia and Levels of Chemokines (CCL5 and CCL11) and IL-5 in Bronchoalveolar Lavage Fluid of Patients With Mustard Gas-Induced Pulmonary Fibrosis

Therefore, this study was designed to analyze the bronchoalveolar lavage (BAL) fluid concentrations of IL-5, RANTES (CCL5) and eotaxin (CCL11) and also to examine the relationship between the percentage and absolute number of the BAL eosinophils and these measured chemokines in patients with sulfur mustard (SM) gas-induced pulmonary fibrosis (PF). Fifteen veterans with mustard gas-induced PF and 14 normal veterans as control group. Pulmonary function tests, tests for D(LCO), computed tomography scans of the chest, analyses of BAL fluids for RANTES (CCL5), eotaxin (CCL11), and IL-5 were performed in all cases. Eosinophilic alveolitis was the predominant feature (p < 0.0001). There were significant differences in CCL5, CCL11, and IL-5 levels of BAL fluid between patients with PF and controls (p < 0.0001, p < 0.0001, and p = 0.001, respectively). The concentrations of CCL5 and CCL11 showed positive correlations with percentage (r = 0.57 and p = 0.03; r = 0.52 and p = 0.04, respectively) and absolute counts (r = 0.54 and p = 0.04, r = 0.53 and p = 0.04, respectively) of BAL eosinophils. There were significant positive correlations between the concentrations of IL-5 and the proportion and total cell number of eosinophils in BAL (r = 0.67 and p = 0.01; r = 0.59 and p = 0.02, respectively) too. A significant correlation between BAL CCL5, CCL11, and IL-5 levels and eosinophils in patients with pulmonary fibrosis due to SM gas inhalation has been demonstrated, suggesting that these C-C chemokines and IL-5 contribute to the recruitment of eosinophils cells in the lung in these victims.

Relationship Between Eosinophilia and Levels of Chemokines (CCL5 and CCL11) and IL-5 in Bronchoalveolar Lavage Fluid of Patients with Mustard Gas-induced Pulmonary Fibrosis

Therefore, this study was designed to analyze the bronchoalveolar lavage (BAL) fluid concentrations of interleukin-5 (IL-5), normal T cell expressed and presumably secreted (RANTES; CCL5), and eotaxin (CCL11) and also to examine the relationship between the percentage and absolute number of the BAL eosinophils and these measured chemokines in patients with sulfur mustard (SM) gas-induced pulmonary fibrosis (PF). Included in this study were fifteen veterans with mustard gas-induced PF and 14 normal veterans as control group. Pulmonary function tests (PFTs), tests for D (LCO), computed tomography (CT) scans of the chest, analyses of BAL fluids for RANTES (CCL5), eotaxin (CCL11), and IL-5 were performed in all cases. Eosinophilic alveolitis was the predominant feature (p < 0.0001). There were significant differences in CCL5, CCL11, and IL-5 levels of BAL fluid between patients with PF and controls (p < 0.0001, p < 0.0001, and p = 0.001, respectively). The concentrations of CCL5 and CCL11 showed positive correlations with percentage (r = 0.57 and p = 0.03, r = 0.52 and p = 0.04, respectively) and absolute counts (r = 0.54 and p = 0.04, r = 0.53 and p = 0.04, respectively) of BAL eosinophils. There were significant positive correlations between the concentrations of IL-5 and the proportion and total cell number of eosinophils in BAL (r = 0.67 and p = 0.01; r = 0.59 and p = 0.02, respectively) too. A significant correlation between BAL CCL5, CCL11, and IL-5 levels and eosinophils in patients with pulmonary fibrosis caused by SM gas inhalation has been demonstrated, suggesting that these C-C chemokines and IL-5 contribute to the recruitment of eosinophils cells in the lung in these victims.

Epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia) of the orbit: a case report

BackgroundAngiolymphoid hyperplasia with eosinophilia (ALHE) and Kimura's Disease (KD) share many clinical and histopathological features. Although they were once considered different stages of the same disease, they are now known to represent separate entities. Recently, ALHE is being called epithelioid hemangioma (EH), a term that better describes the possible neoplastic nature of the entity.Case PresentationAn eighteen year-old Asian female presented with a three-month history of fluctuating swelling and ptosis of the left upper eyelid. Computed tomography disclosed a distinct homogeneous lesion in the left superior orbit, molding to the globe and other orbital structures. At histopathological evaluation the lesion was composed of numerous blood vessels lined by plump endothelial cells with oval nuclei protruding into the lumen. Surrounding the vessels, there was a chronic inflammatory infiltrate with a large proportion of eosinophils. Based on clinical and histopathological findings, the diagnosis of EH was made.ConclusionAlthough exams like blood count, urinalysis and whole body scans can assist in the differential diagnosis, EH can be diagnosed and differentiated from KD on histopathological grounds. The presence of vascular hyperplasia with plump endothelial cells protruding into the lumen is the most important discriminator in establishing the diagnosis of EH. Such distinction is crucial for the patient because EH is not associated with any of the systemic manifestations present in KD.

Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD

Background:Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it...

Bronchoalveolar Lavage in Interstitial Lung Diseases: Does the Recovery Rate Affect the Results?

Background: Bronchoalveolar lavage (BAL) is an established diagnostic tool in interstitial lung diseases. BAL frequently yields findings of diagnostic value and at times even confirmatory diagnostic results. Objectives: The present study has been designed to investigate whether the recovery rate affects BAL results relative to the instilled volume. Methods: Six hundred and eighteen patients with the following diagnoses were included into the study: 236 with sarcoidosis, 85 with idiopathic pulmonary fibrosis, 83 with cryptogenic organizing pneumonitis, 64 with connective tissue disease affecting the lungs, 54 with respiratory bronchiolitis with interstitial lung disease, 51 with extrinsic allergic alveolitis and 45 control patients. BAL was performed during flexible bronchoscopy with an irrigation volume of 100 ml 0.9% saline solution in 5 aliquots of 20 ml each. Only patients with a recovery of at least 30 ml were evaluated. Initially, the entire patient population was analysed, followed by an analysis within the different diagnostic groups and a comparison between patients with a high (>50 ml) and low (≤50 ml) recovery rate. Results: The recovery rate varied between the diagnostic groups (p < 0.001) and was negatively correlated with age (r = –0.21, p < 0.001) and smoking history (r = –0.11, p < 0.035). There were no correlations with inspiratory vital capacity (%pred.; p = 0.26) and forced expiratory volume in 1 s (%pred.; p = 0.15), but a positive correlation with the index (forced expiratory volume in 1 s/inspiratory vital capacity) × 100 (r = 0.23, p < 0.001). The cellular and non-cellular constituents of BAL were not affected by the recovery: cells/millilitre BAL (p = 0.71), relative proportion of macrophages (p = 0.92), lymphocytes (0 = 0.33), neutrophils (p = 0.14) and eosinophils (p = 0.11), albumin concentration (p = 0.13), and proportion of albumin in total protein (p = 0.06). The same applied for the lymphocyte surface markers CD4 (p = 0.72) and CD8 (p = 0.53). In the group with a high recovery rate, patients with sarcoidosis had a lower proportion of eosinophils (p = 0.04) and patients with cryptogenic organizing pneumonitis a higher concentration of albumin (p = 0.02) and lymphocytes (p = 0.007). Otherwise, no further differences were detected. Conclusions: The recovery rate hardly affected the cellular and non-cellular constituents of BAL at a lower limit of 30% of the instilled volume.

The Nature of Immunological Reaction in the Peripheral Airways of Cigarette Smokers

The influence of tobacco smoke on human health is still an important problem worldwide. Complex inflammatory processes and changes in the immune system are crucial in the pathogenesis of smoking related disorders like chronic obstructive lung disease (COPD), lung cancer, asthma, interstitial lung diseases (ILD) and atherosclerosis. The objective of this review is to present the alterations in the immune system in smokers. Discrete changes in peripheral blood of smokers may be found, such as leukocytosis and elevated proportion of T cells. However, the mainly affected system is the respiratory tract. In bronchial epithelium, metaplastic and dysplastic changes are accompanied by elevated expression of adhesion molecules and secretion of many proinflammatory cytokines. In the population of pulmonary macrophages, an elevated proportion of cells, changes in expression surface markers: CD14, CD54, CD11 and CD71 with impaired phagocytic and antigen presenting function were observed. The influence of tobacco smoke on the population of granulocytes results in elevated proportion of neutrophils and eosinophils and elevated concentration of the products of neutrophils: neutrophil elastase (NE), interleukin- 8 (IL-8) and tumor necrosis factor (TNFα). Tobacco smoke seems to alter the way of death of neutrophils from apoptosis to necrosis. On the other hand, an elevated expression of the receptors of apoptosis on lymphocytes was found. Cigarette smoke enhances the recirculation of lymphocytes, which results in the augmentation of activated and cytotoxic/ suppressor cells in the bronchial lumen. Smoking cessation is the most effective method of prophylaxis and treatment of diseases related to tobacco smoking. However, many immunological changes in smokers are not completely reversible after quitting smoking.

Apoptotic eosinophils in sputum from asthmatic patients correlate negatively with levels of IL-5 and eotaxin

Eosinophilic inflammation of the airways is a key characteristic of asthma. A defect in eosinophil apoptosis might contribute to the chronic tissue eosinophilia associated with asthma. Our purpose was to examine whether the occurrence of apoptotic eosinophils in induced sputum from asthmatic patients correlate with interleukin (IL)-5 and eotaxin. Thirty stable and 30 exacerbated asthmatic patients were recruited. Twenty healthy subjects were enrolled as a control group. Induced sputum was obtained from asthmatic patients and from control subjects. The number of apoptotic eosinophils in sputum was assessed by flow cytometry. In sputum supernatant, eosinophil cationic protein (ECP) was measured by sensitive radioimmunoassay, and IL-5 and eotaxin by sandwich enzyme linked immunosorbant assay. Levels of eosinophils, apoptotic eosinophils, IL-5, ECP and eotaxin from asthmatic patients were higher than those from healthy subjects. Thirty exacerbated asthmatics showed higher proportions of eosinophils (median 29.3%, range 13.4%-40.9%), more detectable levels of IL-5 (50.44, 32.99-67.01 pg/ml) and eotaxin (644.6, 197.4-937.7 pg/ml) in their sputum than the patients with stable asthma (P<0.05). There were significant inverse correlations between the levels of sputum IL-5 and the proportion of sputum eosinophil apoptosis in patients with exacerbated and stable asthma (r=-0.85 and -0.79, P<0.01 and P<0.05, respectively). Also inverse correlations were found between the levels of eotaxin and the proportion of sputum eosinophil apoptosis in exacerbated (r=-0.85, P<0.01), or stable asthma (r=-0.69, P<0.05). Additional positive correlations between the levels of sputum IL-5 and eotaxin in either exacerbatated (r=0.93, P<0.01) or stable asthma (r=0.82, P<0.05) were observed. Apoptosis of eosinophils might be suppressed by proinflammatory cytokines and chemokines such as IL-5 and eotaxin leading to their accumulation in the lung. Stimulation of eosinophils in airway with IL-5 and eotaxin may play a crucial role in allergic inflammation.

Cost-Effectiveness of Various Diagnostic Approaches for Occupational Asthma

Diagnosis of occupational asthma (OA) by specific inhalation challenge (SIC) can be costly and is not always available. The use of sputum testing to avoid this in some patients may be a more cost-effective alternative. To compare the cost-effectiveness of SIC with serial measurements of sputum cell counts (sputum testing) and peak expiratory flow (PEF) monitoring. Clinical data and testing costs for OA in 49 patients were collected during a previously published trial, modelled and compared using TreeAge Pro. Clinical outcome was the percentage of accurately diagnosed patients, using SIC as the gold standard. The PEF approach used the most accurate assessment of five experts who were blinded to SIC results. Differences in the proportion of eosinophils during periods on and off work were used for the sputum testing approach and in PEF/sputum for the combined approach. Unit costs were estimated from charges in Canadian hospitals. Data were analyzed by one-way and two-way analyses, and by probabilistic sensitivity analysis using a Monte Carlo simulation technique. The PEF approach had an estimated accuracy of 52% and cost $365 per patient tested. Compared with PEF monitoring, sputum testing was more accurate and cost an estimated $255 for each additional OA patient correctly diagnosed. SIC costs per additional correct diagnosis were $11,032 compared with sputum testing and $6,458 compared with PEF monitoring. The combined PEF/sputum testing approach was not cost-effective in the base case analysis, but cannot be excluded according to probabilistic sensitivity analyses. Although SIC remains the reference test to diagnose OA, when this test is not available, sputum testing is a cost-effective alternative to PEF for diagnosis of OA.

The genetic resistance to gastro-intestinal strongylids in Appenninica sheep: relationship among parasitical load and haematological parametersxs

Faecal Egg Count (FEC) is generally considered a simple but effective parameter for estimating resistance to strongylids, due to its phenotypic relationship to the total number of parasites present in the animal. Nevertheless, also haematological indicators have been shown to be useful in measuring gastro-intestinal nematode resistance in sheep, such as Packed Cell Volume (PCV), number of leukocytes, proportion of eosinophils and plasma albumin. The study was conducted in a single herd of Appenninica sheep situated in Tuscany (Italy) with the aim of studying the relationship among parasitic load of gastro-intestinal Strongylids and haematological parameters. Faecal samples from 54 sheep were collected in four different withdrawals (April, May, September and November 2004) and analysed in order to determine parasite EPG (Eggs Per Gram), using the McMaster technique. At the same time as the faecal samples, blood samples were also collected in order to determine PCV, total proteins, complement proteins, plasma albumin, erythrocytes and eosinophils.Considering the low infection level in spring (April and May), it was believed that animals with a positive EPG in this season could already be considered “not resistant”, although a limited infection (EPG<200) might serve as an index of host’s capacity to keep the parasite population under control. Consequently, we defined as “resistant group” (RG) the subjects with an average value in the spring sample equal to zero EPG, “intermediate resistant group” (IRG) the subjects with an average value under 200 EPG and “not resistant group” (NRG) the animals with an average value over 200 EPG. NRG subjects always showed lower values of PCV (an indicator of anaemia) than the other groups. In September, NRG subjects also showed significantly lower values of eosinophils (3.28%) compared to the other groups (6.54 and 6.20%, respectively, for IRG and RG, P<0.01) and higher values of complement (20.06 vs. 12.61 and 12.77, respectively, for IRG and RG, P<0.05). On the contrary, in November, NRG subjects showed lower values of complement (7.78) than the other groups (19.00 and 15.23, respectively, for IRG and IR, P<0.01).

How Viral Infections Cause Exacerbation of Airway Diseases

Exacerbations of asthma and COPD are major causes of morbidity, mortality, and health-care costs. Over the last decade, studies using new molecular diagnostic techniques have established that respiratory viruses are a major cause of exacerbations of both asthma and COPD. The most prevalent viruses detected during exacerbations are the rhinoviruses. Despite the burden of disease associated with exacerbations, little is known about the mechanisms of virus-induced exacerbations of airway diseases. Exacerbations are associated with increased airway inflammation in patients with both asthma and COPD, but many questions remain unanswered regarding the key inflammatory cells and mediators involved. Identifying the key inflammatory mediators involved in exacerbations holds the promise of developing diagnostic and prognostic markers of exacerbation. In addition, such studies can identify new therapeutic targets for the development of novel drugs for the prevention and treatment of exacerbations.

Acquired cervical scoliosis attributed to Parelaphostrongylus tenuis infection in an alpaca

A 2-year-old alpaca was evaluated because of acute onset of cervical scoliosis. Physical examination revealed severe scoliosis of the caudal portion of the cervical vertebral column with a C-shaped curvature to the right side. No gait deficits were observed. Cervical radiography confirmed severe curvature of C4 to C6 but did not reveal any bony changes. Cerebrospinal fluid had high total protein concentration and extremely high nucleated cell count with a high proportion of eosinophils, suggesting parasitic infection. The alpaca was treated for suspected parelaphostrongylosis with ivermectin, fenbendazole, flunixin, vitamin E, thiamine, physical therapy, and a custom-made neck brace. The alpaca's condition continued to deteriorate, and it developed tetraparesis and ataxia and was euthanized after approximately 1 month. Microscopic evaluation of the cervical spinal cord revealed marked vacuolar changes in the left medial portion of the ventral funiculus, mild lymphoplasmacytic infiltration, and multifocal granulomas. The lesions were continuous from C1 to C7 and were compatible with parasite migration. To the authors' knowledge, this is the first report of acquired scoliosis in an alpaca, which appears to represent an unusual manifestation of parelaphostrongylosis that was reported in horses.

Intractable Otitis Media with Eosinophils: Importance of Diagnosis and Validity of Treatment for Hearing Preservation

This study investigated hearing levels in cases of intractable otitis media with eosinophils and validated the treatment strategy. Medical charts were reviewed retrospectively. The diagnosis was made when the proportion of eosinophils in middle ear secretions exceeded 10%. Twelve patients were identified and treated with an antihistaminergic agent, leukotriene receptor antagonist and topical steroid. The air-bone conductance gap decreased significantly with the relief of subjective symptoms. Bone conduction hearing levels at 4 and 8 kHz were higher than at lower frequencies. There was a significant correlation between subjective symptom duration and bone conduction hearing level at 8 kHz, which diminished with treatment. Compared with suppurative otitis, active otitis with eosinophilia damages high-tone sensory hearing in a time-dependent manner, and antiallergic treatment prevents progression of the high-tone sensory hearing loss. We emphasize the importance of diagnosis and the validity of treatment for intractable otitis media with eosinophils.

Inflammatory subtypes in asthma: Assessment and identification using induced sputum

The authors sought to investigate the detection of non-eosinophilic asthma using induced sputum. Although this is an important subtype of clinical asthma, its recognition is not standardized. Adult non-smokers with asthma and healthy controls underwent sputum induction and hypertonic saline challenge. Non-eosinophilic asthma was defined as symptomatic asthma with normal sputum eosinophil counts. The normal range for sputum eosinophil count was determined using the 95th percentile from the healthy control group as a cut-off point. The recognition of non-eosinophilic asthma using eosinophil proportion was in agreement with a definition based on absolute eosinophil count (kappa 0.67). Non-eosinophilic asthma was a stable subtype over both the short term (4 weeks) and longer term (5 years, kappa 0.77). Airway inflammation in asthma could be categorized into four inflammatory subtypes based on sputum eosinophil and neutrophil proportions. These subtypes were neutrophilic asthma, eosinophilic asthma, mixed granulocytic asthma and paucigranulocytic asthma. Subjects with increased neutrophils (neutrophilic asthma and mixed granulocytic asthma) were older and had an increased total cell count and cell viability compared with other subtypes. Induced sputum eosinophil proportion is a good discriminator for eosinophilic asthma, providing a reproducible definition of a homogenous group. The remaining non-eosinophilic subjects are heterogeneous and can be further classified based on the presence of neutrophils. These inflammatory subtypes have important implications for the investigation and characterization of airway inflammation in asthma.

Increased Expression of Matrix Metalloproteinase-2, Matrix Metalloproteinase-9 and Matrix Metalloproteinase-13 in Lesional Skin of Bullous Pemphigoid

Background: Matrix metalloproteinase (MMP)-2, MMP-9 and MMP-13 can degrade type IV collagen which is the major component of the basement membrane zone (BMZ). In bullous pemphigoid (BP), the separation occurs within the BMZ. Objective: To evaluate the involvement of MMPs in the pathogenesis of BP, we examined the expression of MMP-2, MMP-9 and MMP-13 in the lesional skin of BP patients. Methods: The expression of MMP-2, MMP-9, MMP-13, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 was analyzed by immunohistochemistry in the lesional skin of BP patients in comparison with that in normal human skin. Next, the cellular sources of MMP-2, MMP-9 and MMP-13 were analyzed by double immunohistochemistry. Finally, the levels of these MMPs in the serum and blister fluid of BP patients were measured by ELISA. Results: The number of cells expressing MMP-2, MMP-9 and MMP-13 were significantly increased in the lesional skin of BP patients as compared to that in normal skin. Although the number of cells expressing TIMP-1 and TIMP-2 were also increased in the lesional skin of BP patients as compared to that in normal skin, the ratio of MMPs to TIMPs in the lesional skin of BP patients was high (2.4:1). T cells comprised the major source of MMP-2, MMP-9 and MMP-13, while a proportion of mast cells and eosinophils also expressed these MMPs. Furthermore, marked expression of MMP-2 was detected in the epidermal keratinocytes. The levels of these MMPs in the blister fluid were significantly greater than those in the serum. Conclusion: These results suggest that MMP-2, MMP-9 and MMP-13 may be involved in the mechanism of blister formation in BP and that besides infiltrating inflammatory cells, structural cells like epidermal keratinocytes may also participate in the induction of blister formation in BP.

TGF-β1 Expression in Renal Allograft Rejection and Cyclosporine A Toxicity

To assess short- and long-term influence of the TGF-beta1 on renal allografts. Expression of TGF-beta1 and TNF-alpha, and the proportion of macrophages and eosinophils in interstitium were evaluated in 64 cases including five cases with nonrejected kidneys (NRK), 18 cases with acute rejection (AR), 26 cases with chronic allograft nephropathy (CAN), and 15 cases with acute cyclosporine A (CsA) toxicity. Follow-up biopsies of all cases with AR and CsA toxicity were evaluated for development of interstitial fibrosis (IF) and graft atherosclerosis (GAS). Additionally, influence of tubular-TGF-beta1 expression on graft function during 6 months after the diagnostic biopsy was evaluated. A significant differences was seen between rejected kidneys and acute CsA toxicity in regards of tubular TGF-beta1 expression that patients with CsA toxicity exhibited significantly higher grade of tubular TGF-beta1 expression than patients with AR (P<0.05) and CAN (P<0.05). A significant difference was found between the grades of tubular TGF-beta1 expression in regards to graft function of cases with AR and CsA toxicity (P<0.05). Higher grade tubular TGF-beta1 expression showed better graft function during 6 months. Besides the degree of renal TGF-beta1 expression was positively correlated with development of diffuse IF and GAS (P<0.05) that the risk of the IF and GAS was higher in cases with grade 2 renal TGF-beta1 expression. Despite the short-term posttransplantation tubule-repairing effects of TGF-beta1, the overall effects of TGF-beta1 in the kidney seem to be negative that increased expression of TGF-beta1 promotes IF and vasculopathy associated with CAN.