Serial Assessment of Immune Status by Circulating CD8+ Effector T Cell Frequencies for Posttransplant Infectious Complications

To clarify the role of CD8+ effector T cells for infectious complications, 92 recipients were classified according to the hierarchical clustering of preoperative CD8+CD45 isoforms: Group I was naive, Group II was effector memory, and Group III was effector (E) T cell-dominant. The posttransplant infection rates progressively increased from 29% in Group I to 64.3% in Group III recipients. The posttransplant immune status was compared with the pretransplant status, based on the measure (% difference) and its graphical form (scatter plot). In Groups I and II, both approaches showed a strong upward deviation from pretransplant status upon posttransplant infection, indicating an enhanced clearance of pathogens. In Group III, in contrast, both approaches showed a clear downward deviation from preoperative status, indicating deficient cytotoxicity. The % E difference and scatter plot can be used as a useful indicator of a posttransplant infectious complication

IL-33 and RANTES( Regulated on Activation, Normal T Cell Expressed and Secreted) in BAL Fluid in Asthma Patients Without Cigarette Smoking

Background:Inflammatory cytokines and chemokines have been reported to play important roles in thepathogenesis of bronchial asthma. However, no criteria for the classification of `smoker\u27 and `atopic\u27 in bronchialasthma have been defined. In this study, we compared the levels of several cytokines found in thebronchoalveolar lavage( BAL) fluid of patients classified as having bronchial asthma.Methods:Cell subpopulations in BAL fluid were counted. BAL fluid levels of interleukin( IL)-4, -5, -13,-17, and -33 and RANTES (regulated on activation, normal T cell expressed and secreted were measuredusing a bead suspension array in 36 asthma patients (13 males, 23 females;mean age, 39.5±92.8 years)who were non-smokers, 18 asthma patients( 11 males, 7 females;mean age, 30.7±2.7 years) who were exor current smokers( Brinkman index( BI):1&#8722;399), and 10 asthma patients( 9 males, 1 female;mean age,50.2±5.5 years) who were current heavy smokers( BI:&#8805; 400). Relationships were assessed by Spearman\u27srank correlation analysis.Results:The number of lymphocytes in BAL cell subpopulations of non-smokers( 25±7×103/ml) weresignificantly (p<0.05) higher than those of heavy smokers (12±3×103 /ml). The number of neutrophilswas significantly( p<0.05) higher in heavy smokers( 18±9×103/ml) than in non-smokers( 4±2×103/ml).Levels of IL-33 and RANTES were significantly (P<0.05) higher in non-smokers (26.1±7.3 pg/ml and42.8±10.3 pg/ml, respectively) than in heavy smokers (13.7±4.5 pg/ml and 27.4±5.4 pg/ml, respectively).In addition, the levels of IL-33 and RANTES in non-smokers were significantly( P<0.05) higher in atopicasthma patients (33.0±9.8 pg/ml and 47.8±14.0 pg/ml, respectively) than in non-atopic asthma patients(9.1±3.8 pg/ml and 29.5±7.8 pg/ml, respectively). A good correlation was noted between RANTES andlymphocytes (R=0.365, P<0.05) or IL-33 (R=0.561, P<0.05) in atopic asthma patients who were nonsmokers.Conclusions:Differences in the cell types of BAL fluid, as well as in the levels of IL-33 and RANTES inasthma patients with or without smoking, might reflect pathogenesis

Mechanism of Airway Remodeling Induced by Repeated Inhalation of Methacholine in a Mouse Model of Asthma

Background:Increased severity of asthma is contributed by airway tissue remodeling, which may be associated with chronic allergic inflammation. A recent study revealed the potential capacity of repeated bronchoconstriction, e.g. induced by a muscarine agonist, methacholine(Mch)challenge, to involve in airway remodeling, even though allergic inflammation is not implicated. We have evaluated the influence of repeated bronchoconstriction induced by Mch inhalation on airway remodeling in a murine model of asthma and have examined its machanisms. Methods:Mice were immunized with ovalbumin(OVA), and consequently, challenged by either daily OVA inhalation(the OVA group;a model of asthma with allergic inflammation)or daily Mch inhalation(the Mch group;a model of asthma without allergic inflammation). Lung tissues were obtained and were evaluated histologically after 5, 10, and 15 consecutive inhalation challenges of both OVA and Mch.Results:Eosinophilia in the airway observed only on the OVA group. Subepithelial collagen-band thickness increased also in the OVA group(p<0.01)after 15 challenges, but not in the Mch group. Significant increase in thickness of airway smooth muscle layer and the number of goblet cells were revealed in both the OVA and Mch group after 10(p<0.05 and p<0.01, p<0.01 and p<0.05, respectively, for the comparison of the two challenge groups with the control group)and 15 challenges(p<0.05 and p<0.01, both p< 0.01, respectively, for the comparison with control), further, all these measurements were greater in the OVA group than in the Mch group after both 10 and 15 challenges(both p<0.05 and p<0.01, respectively). An increase in mast cell counts within the airway wall was shown in the OVA group after 10 challenges (p<0.01 compared with control), not in the Mch group at all. Epithelia expression of transforming growthfactor b (TGF-b)increased in both challenge groups after 15 challenges(both p<0.05 compared with control), and was higher than in Mch(p<0.05).Conclusion:Repeated Mch inhalation may induce airway remodeling, while comparatively mild, potentially resulting in progressive severity of asthma. The results implicate that the potential risk associated with Mch challenge should be considered

Involvement of Bird-related IgG Antibodies in Interstitial Pneumonia

Background and Objective:Chronic interstitial pneumonia (IP) might include chronic hypersensitivity pneumonitis (HP) and chronic bird-related hypersensitivity pneumonitis (BRHP). A specific antigen is difficult to identify in these diseases, and such evidence would provide important clues suggesting a diagnosis of HP. In this study, we used an ImmunoCAP analysis system to measure specific IgG antibodies against pigeons and budgerigars in the sera of patients with IP and investigated the involvement of bird-related IgG antibodies in IP.Methods:The study group comprised 22 patients with idiopathic pulmonary fibrosis (IPF), 8 with chronic IP, 7 with subacute HP, 7 with chronic HP, and 10 with control diseases. All cases were diagnosed from 2000 through 2011 at the Institute of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University. Clinical features, results of laboratory examinations, and levels of serum IgG antibodies against pigeons and budgerigars were compared.Results:There were no significant differences among the disease groups in C-reactive protein, leukocyte count, lactate dehydrogenase, and the results of blood gas analysis. KL-6 and surfactant protein D were significantly higher in subacute HP and chronic HP. The levels of anti-pigeon IgG antibodies and anti-budgerigar IgG antibodies in each disease group were respectively as follows:IPF, 11.02±5.97&#8200;mg/l, 5.03±3.97&#8200;mg/l;chronic IP, 10.04±8.55&#8200;mg/l, 3.30±1.47&#8200;mg/l;subacute HP, 14.39±9.13&#8200;mg/l, 7.96±6.47&#8200;mg/l;chronic HP, 24.97±16.19&#8200;mg/l, 11.50±13.80&#8200;mg/l;and control diseases, 8.66±3.15&#8200;mg/l, 3.77±1.05&#8200;mg/l. The mean levels of anti-pigeon IgG antibodies and anti-budgerigar IgG antibodies were significantly higher in chronic HP. There was a positive correlation between anti-pigeon IgG antibodies and anti-budgerigar IgG antibodies (R2 = 0.715, p<0.001). Conclusions:In patients with clinically diagnosed chronic HP, high levels of anti-pigeon IgG antibodies or anti-budgerigar IgG antibodies were confirmed using an ImmunoCAP analysis system. In general, HP (especially chronic HP) is difficult to diagnose definitively, and this analysis system is expected to facilitate diagnosis

Clinical Characteristics of Acute Exacerbations of Idiopathic Pulmonary Fibrosis and Involvement of Viral, Mycoplasma pneumoniae, and Chlamydophila pneumoniae Infections

Background and Objective:To clarify the clinical characteristics of acute exacerbation of idiopathic pulmonaryfibrosis (IPF) and the involvement of infections with pathogenic microorganisms and viruses inacute exacerbation.Methods:During the 12 years from 2000 through 2011, we studied 50 patients who were admitted andreceived treatment for acute exacerbation of IPF in our department. Demographic characteristics, imagingfindings, laboratory findings, changes in antibody titers against bacteria, Mycoplasma pneumoniae, Chlamydophilapneumoniae, and known viruses, and outcomes were studied.Results:Among the 50 patients with acute exacerbation of IPF( 41 men and 9 women) 29 patients died(mortality rate, 58.0%). Computed tomography showed subpleural peripheral ground-glass opacities( GGO)in 5 patients, multiple patchy GGO in 19, and diffuse GGO in 26. Only the PaO2/FiO2 ratio was significantlylower in the non-survivors compared with survivors. Three patients had high titers of IgM antibodiesagainst C. pneumoniae, but acute infection was ruled out by the changes in IgA and IgG antibodies in pairedserum samples. Antibody titers against known viruses significantly increased in 2 patients( respiratory syncytialvirus in 1 and adenovirus 11 in 1). In acute-phase serum samples, 7 patients had increased antibodytiters against parainfluenza virus 3, resulted in no significant change in paired serum samples.Conclusions:Our results suggest that known pathogens do not play a role in acute exacerbation of IPF.The outcomes of IPF remain poor, and the elucidation of the causes and pathological features of acute exacerbationof IPF, including the identification of unknown pathogens, is awaited

Clinical Significance of Propionibacterium acnes in the Formation of Noncaseating Epithelioid-Cell Granulomas of the Mediastinal Lymph Nodes and Lung in Patients with Lung Cancer:Differential Diagnosis Between Sarcoid Reactions and Sarcoidosis

Objectives:Sarcoidosis is a systemic noncaseating epithelioid-cell granulomatous disease of unknown origin.Granulomas occurring around malignant tumors and regional lymph nodes can be caused by sarcoid reactions.The mechanisms underlying sarcoidosis and sarcoid reactions remain unclear. Whether increaseduptake of fluorodeoxyglucose( FDG) in lymph nodes on positron emission tomography( PET) is caused bytumor metastasis, the concurrent presence of sarcoidosis, or sarcoid reactions must be determined to ensureproper disease staging and selection of treatment policy. We studied patients who underwent surgery forlung cancer and had no histopathological evidence of lymph-node metastasis in whom concurrent sarcoidosisor sarcoid reactions were diagnosed.Methods:In six patients who underwent surgery for primary lung cancer, granulomatous lesions werehistopathologically studied in dissected lymph nodes and lung. Tissue sections were stained with monoclonalantibodies against Propionibacterium acnes( PAB antibodies).Results:The six patients had noncaseating epithelioid-cell granulomas in mediastinal lymph nodes andlung. Clinically, concurrent sarcoidosis was suspected, but the results of staining the tissue specimens withPAB antibodies( in granulomas, alveolar macrophages, Hamazaki-Wesenberg bodies, and lymphatic sinuses)suggested sarcoid reactions in 5 patients. In one patient in whom granulomas stained positive with PAB antibodies,concurrent sarcoidosis was diagnosed.Conclusions:In patients with lung cancer who have no distinct systemic evidence of sarcoidosis, thepresence of noncaseating epithelioid-cell granulomas in the lung hilum or mediastinum is usually caused bysarcoid reactions

A Case of Pulmonary Benign Metastasizing Leiomyoma Occurring after Uterine Myomectomy

Benign metastasizing leiomyoma (BML) is a very rare disease, and although it was reported as early as1939 to result from metastasis of benign uterine myoma to the lungs and lymph nodes, its pathology remainsobscure. Here, we describe a case of pulmonary BML occurring after uterine myomectomy in a42-year-old woman. She presented with a 2-week history of dry cough on exertion. Chest radiography andcomputed tomography( CT) revealed bilateral multiple nodular lesions. The patient had a history of uterinemyoma and previously underwent myomectomy. For definitive diagnosis, lung biopsy was performed byvideo associated thoracoscopic surgery. Histopathologic examination of biopsy specimens revealed pulmonaryBML occurring after uterine myomectomy. For treatment of the pulmonary BML, gonadotropin-releasinghormone was initially administered, and 1 month later the patient underwent complete hysterectomyand bilateral salpingo-oophorectomy. Chest CT 6 months after surgery showed that the size and number oflung multiple nodular lesions did not increase compared with those before surgery. In future studies, we aimto investigate a larger number of pulmonary BML cases, as well as establish specific treatments and investigatethe prognosis of the disease.Abbreviations:BML:benign metastasizing leiomyomaSS:Sj&ouml;gren\u27s syndromeCT:computed tomographyH&E:hematoxylin and eosinVATS:video associated thoracoscopic surgeryCA:carbohydrate antigenIg:immunoguloblina SMA:a smooth muscle acti

A Case of Inflammatory Lung Disease and Retroperitoneal Fibrosis Attributed to Systemic IgG4-related Disease

Recently, immunoglobulin (Ig) G4-related diseases such as autoimmune pancreatitis (AIP), sclerosingsialadenitis, retroperitoneal fibrosis, and sclerosing cholangitis have been reported. IgG4-related diseases arecharacterized by high serum IgG4 concentrations, sclerosing inflammation with numerous IgG4-positiveplasma cells, and steroid sensitivity, irrespective of their organ of origin. We describe a case of inflammatorylung disease and retroperitoneal fibrosis, suggested to involve IgG4. The patient was a 76-year-old man. Acomputed tomographic scan of the chest showed nodular air-space consolidation in the left upper lobe. Theserum IgG4 concentration was abnormally elevated, but there was no evidence of AIP. Bilateral hydronephrosisassociated with thickened soft tissue around the abdominal aorta had been diagnosed previously. Hehad undergone surgery, and retroperitoneal fibrosis was diagnosed histologically (hematoxylin and eosinstain). Histological examination of bronchoscopic specimens taken from the left S3 region showed mononuclear-cell infiltration of the fibrotic bronchial wall, including many IgG4-positive plasma cells. Specimens ofthe region affected by retroperitoneal fibrosis were retrospectively reanalyzed, and the cells were positivefor IgG4 on immunostaining, similar to the lung tissue. The patient responded to treatment with corticosteroids.In conclusion, the present case shared many clinical and clinicopathological similarities with systemicIgG4-related autoimmune disease. To our knowledge, however, this is the first reported case of inflammatorylung disease with retroperitoneal fibrosis in a patient with systemic IgG4-related autoimmune disease

Analysis of the Characteristics of Patients Presenting with Exacerbation of Asthma to Emergency Care Units

Background:Fatal asthma remains a serious problem, and patient self-management of asthma is important to prevent exacerbation. To reduce the asthma mortality rate, we analyzed the characteristics of patients who visited an emergency care unit with exacerbation of asthma.Methods:Subjects were 317 patients(135 men, 182 women;mean age, 47.0 years)who visited the emergency room at Dokkyo Medical University Hospital or Dokkyo Medical University Koshigaya Hospital for exacerbation of asthma between April 2010 and March 2011. When categorized by severity, 41.3% ofpatients were step 1, 8.2% were step 2, 18.9% were step 3, 30.9% were step 4, and 0.6% were unknown. When categorized by primary care physician, 60.3% of patients had a primary care physician at Dokkyo Medical University, 13.6% had one at another hospital, and 26.2% had no primary care physician. When categorized by recovery from exacerbation, control was achieved within 1 day in 63.1% of cases, after more than 1 day in 30.6% of cases, and required admission in 6.3% of cases.Results:The rate of admissions was highest for cases with step 1 severity(step 1, 55.0%;step 2, 20.0%;step 3, 0.0%;and step 4, 25.0%). The rate of admissions did not differ significantly by age(age 15-39 years, 40.0%;40-65 years, 25.0%;>65 years, 35.0%). Initial value of oxyhemoglobin saturation(SpO_2) measured by pulse oximetry was significantly lower in the admission group(SpO_2 92.4%)than in the nonadmissiongroup(SpO_2 95.2%, p<0.01).Conclusion:Patients with step 1 severity who visit an emergency unit with exacerbation of asthma may need regular treatment for asthma. When initial SpO_2 is less than 92%, we should consider hospitalization for treatment of asthma