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Sample records for asthmatic patients inhibition

  1. Undifferentiated bronchial fibroblasts derived from asthmatic patients display higher elastic modulus than their non-asthmatic counterparts.

    PubMed

    Sarna, Michal; Wojcik, Katarzyna A; Hermanowicz, Pawel; Wnuk, Dawid; Burda, Kvetoslava; Sanak, Marek; Czyż, Jarosław; Michalik, Marta

    2015-01-01

    During asthma development, differentiation of epithelial cells and fibroblasts towards the contractile phenotype is associated with bronchial wall remodeling and airway constriction. Pathological fibroblast-to-myofibroblast transition (FMT) can be triggered by local inflammation of bronchial walls. Recently, we have demonstrated that human bronchial fibroblasts (HBFs) derived from asthmatic patients display some inherent features which facilitate their FMT in vitro. In spite of intensive research efforts, these properties remain unknown. Importantly, the role of undifferentiated HBFs in the asthmatic process was systematically omitted. Specifically, biomechanical properties of undifferentiated HBFs have not been considered in either FMT or airway remodeling in vivo. Here, we combine atomic force spectroscopy with fluorescence microscopy to compare mechanical properties and actin cytoskeleton architecture of HBFs derived from asthmatic patients and non-asthmatic donors. Our results demonstrate that asthmatic HBFs form thick and aligned 'ventral' stress fibers accompanied by enlarged focal adhesions. The differences in cytoskeleton architecture between asthmatic and non-asthmatic cells correlate with higher elastic modulus of asthmatic HBFs and their increased predilection to TGF-β-induced FMT. Due to the obvious links between cytoskeleton architecture and mechanical equilibrium, our observations indicate that HBFs derived from asthmatic bronchi can develop considerably higher static tension than non-asthmatic HBFs. This previously unexplored property of asthmatic HBFs may be potentially important for their myofibroblastic differentiation and bronchial wall remodeling during asthma development. PMID:25679502

  2. Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459.

    PubMed

    Singh, Dave; Cadden, Paul; Hunter, Michael; Pearce Collins, Lisa; Perkins, Mike; Pettipher, Roy; Townsend, Elizabeth; Vinall, Shân; O'Connor, Brian

    2013-01-01

    CRTH2 (chemoattractant receptor expressed on T-helper (Th) type 2 cells) is a G-protein-coupled receptor expressed by Th2 lymphocytes and eosinophils that mediates prostaglandin (PG)D(2)-driven chemotaxis. We studied the efficacy of the oral CRTH2 antagonist OC000459 in steroid-naïve asthmatic patients. A randomised, double-blind, placebo-controlled, two-way crossover study of 16 days' treatment with OC000459 (200 mg twice daily) on the late (LAR) and early (EAR) asthmatic responses to bronchial allergen challenge was conducted, with 16 subjects completing the study. There was a 25.4% (95% CI 5.1-45.6%) reduction in the LAR area under the curve (AUC) for change in forced expiratory volume in 1 s with OC000459 compared with placebo (p=0.018) but no effect on the EAR. Sputum eosinophil counts at 1 day post-allergen challenge were lower after OC000459 treatment (p=0.002). PGD(2)-induced blood eosinophil shape change ex vivo was assessed at day 7 (n=7). The AUC of eosinophil shift for OC000459 was lower than placebo; the mean difference was -33.6% (95% CI -66.8- -0.4%; p=0.048). OC000459 treatment inhibited LAR and post-allergen increase in sputum eosinophils. This CRTH2 antagonist appears to inhibit allergic inflammation in asthma. PMID:22496329

  3. Role of eosinophilic inflammation and atopy in elderly asthmatic patients

    PubMed Central

    Siripongpun, Sitthisak; Rerkpattanapipat, Ticha

    2016-01-01

    Background Asthma in the elderly is severe and associated with poor treatment outcome. Although atopy has an important role in pathogenesis, its role in the elderly is unclear, partly due to immune senescence. Objective We aimed to examine the associations of Th2-mediated inflammation with asthma severity in the elderly. Methods Consecutive asthmatics older than 60 years without severe exacerbation within 8 weeks were enrolled. Atopic status was determined by positive serum specific IgE or skin prick test to common aeroallergens. Serum total IgE was measured simultaneously to exhaled fractional concentration of nitric oxide (FeNO). Asthma control level was assessed by using Thai Asthma Control Test (ACT) score. Results Total of 44 elderly asthmatic patients were enrolled. The mean age was 68.9 years and mean age of asthma diagnosis was 46.6 years. Seventy-seven percent of patients were female. Atopic status was found in 45.5% of patients. Uncontrolled asthma classified as ACT score < 20 was noted in 25% of elderly asthma, but its association with either high serum total IgE (≥120 IU/mL), high FeNO (≥50 ppb) or atopic status was not detected. Conclusion One-fourth of elderly asthmatics were clinically uncontrolled, while atopy was confirmed in 45.5%. Neither high total IgE, high FeNO nor atopic status was associated with uncontrolled asthma in the elderly. Other factors might play role in asthma severity in the elderly, and has to be further investigated. PMID:27489791

  4. [Asthma and scuba diving: can asthmatic patients dive?].

    PubMed

    Sade, Kobi; Wiesel, Ory; Kivity, Shmuel; Levo, Yoram

    2007-04-01

    Self-contained underwater breathing apparatus (scuba) diving has grown in popularity, with millions of divers enjoying the sport worldwide. This activity presents unique physical and physiological challenges to the respiratory system, raising numerous concerns about individuals with asthma who choose to dive. Asthma had traditionally been a contraindication to recreational diving, although this caveat has been ignored by large numbers of such patients. Herein we review the currently available literature to provide evidence-based evaluation of the risks associated with diving that are posed to asthmatics. Although there is some indication that asthmatics may be at an increased risk of pulmonary barotrauma, the risk seems to be small. Thus, under the right circumstances, patients with asthma can safely participate in recreational diving without any apparent increased risk of an asthma-related event. Decisions on whether or not diving is hazardous must be made on an individual basis and be founded upon an informed decision shared by both patient and physician. PMID:17476937

  5. Chlamydia pneumoniae enhances the Th2 profile of stimulated peripheral blood mononuclear cells from asthmatic patients.

    PubMed

    Smith-Norowitz, Tamar A; Chotikanatis, Kobkul; Erstein, David P; Perlman, Jason; Norowitz, Yitzchok M; Joks, Rauno; Durkin, Helen G; Hammerschlag, Margaret R; Kohlhoff, Stephan

    2016-05-01

    Chlamydia pneumoniae is a cause of respiratory infection in adults and children. There is evidence for an association between atypical bacterial respiratory pathogens and the pathogenesis of asthma. We compared T helper (Th) responses in C. pneumoniae - infected peripheral blood mononuclear cells (PBMC) in patients with or without asthma. PBMC (1×10(6)/mL) from asthmatic patients (N=11) and non-asthmatic controls (N=12) were infected or mock-infected for 1h +/- C. pneumoniae TW-183 at a multiplicity of infection (MOI)=1 and MOI=0.1, or cultured for 24h +/- Lactobacillus rhamnosus GG (LGG). Interleukin (IL)-4, IL-10, IL-12, Interferon (IFN)-gamma and total IgE levels were measured in supernatants (ELISA). C. pneumoniae infection led to an increase (>50%) of IgE levels in PBMC from asthmatics, compared with mock-infected on day 10; IgE wasn't detected in non-asthmatics. C. pneumoniae - infected PBMC from asthmatics increased levels of IL-4 and IFN-gamma after 24h, compared with PBMC alone; levels of IL-10 and IL-12 were low. When uninfected-PBMC from asthmatics were LGG-stimulated, after 24h, IL-4 was undetectable, but IL-10, IL-12, and IFN-gamma increased, compared with PBMC alone. Thus, C. pneumoniae infection has the ability to induce allergic responses in PBMC of asthmatics, as evidenced by production of Th2 responses and IgE. PMID:26924667

  6. Asthma Economic Costs in Adult Asthmatic Patients in Tehran, Iran

    PubMed Central

    SHARIFI, Laleh; POURPAK, Zahra; FAZLOLLAHI, Mohammad Reza; BOKAIE, Saied; MOEZZI, Hamid Reza; KAZEMNEJAD, Anoushirvan; MOIN, Mostafa

    2015-01-01

    Background: High prevalence and increasing rate of asthmatic patients around the word witnesses the high burden of asthma. We have limited data on asthma burden and economic costs in Iran. This study aimed to find direct and indirect economic costs of asthma and their association with some background factors in one of the referral tertiary centers for adult patients with asthma. Methods: We surveyed asthma related economic costs of 197 adult patients who referred to Milad Hospital, Tehran, Iran from Jun 2007 to January 2010. The patients were followed up for a period of one-year ±1 month and asthma related costs and its control status were registered. Results: Patients were consisted of 125 (64.1%) females and 70 (35.9%) males. Total cost of asthma was 590.22 ±32.18 USD for one patient per one year, the cost of drug, paraclinic, doctor visit, hospitalization, emergency, transportation, and absent days were 327.02, 4.76, 35.44, 3.82, 0.26, 113.03, 105.89 USD respectively. Men showed a significant elevation in their total (P=0.009) and drug costs (P=0.028). In addition, we found significant differences between total asthma costs and asthma control status (P=0.002). Conclusions: According to the high proportion of asthma, related cost compare to Total Income of an Iranian family, the necessity of public coverage of health assurance is quite clear. We suggest that improving asthma management and accessibility to specialized treatment centers can result in decreasing asthma medication and transportation costs as major direct and indirect asthma related costs. PMID:26587495

  7. High- and low-dose allergen challenges in asthmatic patients using inhaled corticosteroids

    PubMed Central

    Lee, Wha-Yong; Southworth, Thomas; Booth, Steven; Singh, Dave

    2015-01-01

    Aims The inhaled allergen challenge model has been used previously to investigate the effects of novel anti-inflammatory drugs in inhaled corticosteroid (ICS)-naïve asthmatics. The aim of this study was to characterize high- and low-dose allergen challenges in asthmatic patients using ICS. Methods Twenty-eight asthmatic patients taking ICS (beclomethasone equivalent <1000 μg day−1) were recruited for high-dose allergen challenge, of whom 10 subsequently also had a repeat low-dose challenge comprising seven allergen challenges. Induced sputum was collected for measurements of cell counts and supernatant biomarkers. Results The high-dose allergen challenge caused an early and late asthmatic response in 19 of 28 patients; the mean maximal fall in the forced expiratory volume in 1 s (FEV1) was 29.1% (SD 6.2%) and 25.1% (SD 9.6%), respectively. There was also an increase in sputum eosinophils of 6.2% (P = 0.0004), as well as supernatant eosinophil cationic protein levels. The low-dose allergen challenge caused an acute fall in FEV1, but had no effect on FEV1 at 24 h after challenge or sputum measurements. Conclusions The high-dose allergen challenge in asthmatics using ICS induces a late asthmatic response associated with an increase in eosinophilic airway inflammation. This may be a suitable model for studying the effects of novel anti-inflammatory drugs added to maintenance ICS treatment. PMID:25214200

  8. [Oropharyngeal bacteria in asthmatic patients in the city of Maracaibo, Venezuela].

    PubMed

    Arocha-Sandoval, Francisco; Parra-Quevedo, Katynna

    2002-09-01

    Bronchial asthma is an intercurrent disease that affects a major portion of the population. Neither its etiopathogenesis nor its complications have been fully established. The purpose of this study was to determine the composition of oropharyngeal bacterial flora in asthmatic patients and compare it with oropharyngeal bacterial flora in a group of healthy patients in order to establish its relationship with the pathogenesis of asthma and its complications. A sample consisting of 116 pharyngeal swabs was analysed from march 1995 to december 1996. 58 of the total amount of pharyngeal swabs corresponded to asthmatic patients (during asthmatic crisis), while the other 58 corresponded to healthy subjects. Common bacteriological culture techniques were carried out in order to obtain the bacteriological diagnosis. The results showed that isolation of transitory flora bacteria in asthmatic patients was 75.8%, which was significantly higher (p < 0.05) than in the control group (27.5%). Streptococcus pyogenes was the most frequent isolated bacteria in the group of asthmatic patients (17.2%), while Escherichia coli was the most frequent bacteria in the control group. No significant difference was found regarding sex and the presence of transitory flora bacteria. It was also found that enterobacteria and non fermenting negative gram bacillus increased with age in both groups; a higher incidence was observed in the group of 40-year-old subjects. These finding confirm the existence of a relationship between the asthmatic condition and the percentage of transitory bacterial flora carriers. The explanation to this phenomenon might be the frequent use of antibiotics and the possible contamination of the micro-nebulization equipment used for the treating the asthma crisis. This data must be considered when applying empiric therapy in asthmatic patients complicated with pneumonia. The possibility that certain infectious agents, including bacteria, could play a role in asthma

  9. Effects of Exercise Rehab on Male Asthmatic Patients: Aerobic Verses Rebound Training

    PubMed Central

    Zolaktaf, Vahid; Ghasemi, Gholam A; Sadeghi, Morteza

    2013-01-01

    Background: There are some auspicious records on applying aerobic exercise for asthmatic patients. Recently, it is suggested that rebound exercise might even increase the gains. This study was designed to compare the effects of rebound therapy to aerobic training in male asthmatic patients. Methods: Sample included 37 male asthmatic patients (20-40 years) from the same respiratory clinic. After signing the informed consent, subjects volunteered to take part in control, rebound, or aerobic groups. There was no change in the routine medical treatment of patients. Supervised exercise programs continued for 8 weeks, consisting of two sessions of 45 to 60 minutes per week. Criteria measures were assessed pre- and post exercise program. Peak exercise capacity (VO2peak) was estimated by modified Bruce protocol, Forced vital capacity (FVC), Forced expiratory volume in 1 second (FEV1), and FEV1% were measured by spirometer. Data were analyzed by repeated measure analysis of variance (ANOVA). Results: Significant interactions were observed for all 4 criteria measures (P < 0.01), meaning that both the exercise programs were effective in improving FVC, FEV1, FEV1%, and VO2peak. Rebound exercise produced more improvement in FEV1, FEV1%, and VO2peak. Conclusions: Regular exercise strengthens the respiratory muscles and improves the cellular respiration. At the same time, it improves the muscular, respiratory, and cardio-vascular systems. Effects of rebound exercise seem to be promising. Findings suggest that rebound exercise is a useful complementary means for asthmatic male patients. PMID:23717762

  10. Tetracosactrin for the management of asthmatic patients after long-term corticosteroids.

    PubMed Central

    Hugh-Jones, P; Pearson, R S; Booth, M

    1975-01-01

    Thirty-five of 41 asthmatic patients, who had been taking oral corticosteroids regularly for between one and 12 years, recovered their adrenal function after courses of depot tetracosactrin, even those with apparently complete adrenal suppression. They all showed benefit by transfer to depot tetracosactrin, though steroid withdrawal symptoms could be troublesome. Skin pigmentation in three, and two severe reactions to tetracosactrin were encountered. We believe that it is advisable to give depot tetracosactrin when converting severe asthmatics to the use of beclomethasone dipropionate aerosols who have previously been treated by long-term steroids with consequent adrenal suppression. PMID:170703

  11. Relationship between sputum inflammatory markers and osmotic airway hyperresponsiveness during induction of sputum in asthmatic patients.

    PubMed Central

    Jang, A. S.; Choi, I. S.

    2001-01-01

    Hypertonic saline aerosols are being used increasingly for bronchial provocation testing and induction of sputum. The aims of this study were to assess the response to challenge with 3% hypertonic saline administered via a ultrasonic nebulizer in patients with asthma, and to evaluate relationship between % fall of FEV1 during induction of sputum (osmotic airway hyperresponsiveness; osmotic AHR) and biochemical markers of induced sputum. We investigated changes in FEV1 in response to inhaling ultrasonically nebulized 3% saline in 25 patients with asthma and 10 control subjects. FEV1 was measured before, during, and after induction of sputum. We used fluoroimmunoassay to detect eosinophil cationic protein (ECP), immunohistochemical staining to detect EG2+ (secretory form of ECP) eosinophils, and a sandwich ELISA to detect interleukin (IL)-5. Protein concentration was determined by using bicinchoninic acid protein assay reagent. Asthmatics, compared with controls, had significantly higher osmotic AHR. Moderate to severe asthmatics had significantly higher osmotic AHR compared to mild asthmatics. Osmotic AHR was significantly correlated with the proportion of eosinophils, the levels of ECP, EG2+ eosinophils, IL-5, and proteins. These data suggest that osmotic AHR is closely related to the clinical status and biochemical markers of sputum supernatant in asthmatic patients. PMID:11511785

  12. Lung function, asthma paradox, atopy, and risk factors in Mexican spirometry-diagnosed asthmatic patients.

    PubMed

    Recio-Vega, Rogelio; Padua y Gabriel, Antonio; Sánchez-Cabral, Olivia; Ocampo-Gómez, Guadalupe Leticia; Rincón-Castañeda, Cuauthémoc

    2007-01-01

    Despite long-term studies, still not much is known about the asthma triggering factors and its sometimes controversial results. Probably one of the major problems of controversy is the lack of specific and accurate diagnosis of this disease. The aim of this study was to assess lung function, atopy, and environmental factors in spirometry-diagnosed asthmatic patients. Time series of daily counts of hospital emergency admissions were constructed for known asthmatic subjects. Spirometry, chest radiograph, arterial gasometry, skin tests, environmental SO2 levels, and climatic parameters were evaluated. Family asthma history was observed in a high proportion of asthmatic patients and it correlated marginally with severity of asthma. A seasonal trend in asthma frequency was recorded and it was more common in the urban area and in those living in the margins of the city. The most frequent asthma type recorded was the severe persistent asthma. More than 50% of subjects had subresponse to bronchodilator; asthma paradox was recorded in 10.8%. Positive skin tests were observed in 36.9% and SO2 levels did not correlate with asthma attacks. Paradox asthma or tolerance may be developed by asthmatic subjects during chronic treatment with short-acting 92-agonists. To avoid side effects and to decrease the morbidity and mortality associated with the usage of antiasthma medications, it is essential to identify quickly those subjects that respond abnormally to the short-acting P2-agonist. PMID:17619567

  13. Prevalence of vitamin D deficiency and insufficiency among adult asthmatic patients in Karachi.

    PubMed

    Kamran, Afshan; Alam, Syed Mahboob; Qadir, Farida

    2014-11-01

    Vitamin D deficiency has assumed pandemic proportions all over the world. It has been documented as a frequent problem in studies of young adults, elderly person and children in other countries, but there is no reliable data on vitamin D status of adult asthmatic patients in Pakistan. To determine the prevalence of vitamin D deficiency and insufficiency in adult asthmatic patients with moderate to severe asthma using a cross-sectional study design in Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi.311 adult asthmatic patients with moderate to severe asthma were recruited from JPMC, tertiary care hospital in Karachi. Questionnaires were administered together demographics, height, weight, nutritional and physical activity assessment. Blood samples for vitamin D measurement were also taken. Results show high prevalence of vitamin D deficiency and insufficiency (88.10%) in adult patients with moderate to severe persistent asthma. Vitamin D deficiency and insufficiency was more frequently observed in female than in male patients.67.66% of the female patients had serum vitamin D level less than 20 ng/ml as compare to 56.1% of the male patients (p=0.01). PMID:26045376

  14. Lower airway inflammation and hyperresponsiveness in non-asthmatic patients with non-allergic rhinitis

    PubMed Central

    Wang, Qiuping; Ji, Junfeng; Xie, Yanqing; Guan, Weijie; Zhang, Yong; Wang, Zhiyi; Wu, Kunmin

    2015-01-01

    Background Potential associations between non-allergic rhinitis (NAR) and asthma have been verified epidemiologically, but these associations remain not very clear. It is necessary to further explore the possible implication of lower airway abnormities in NAR patients but without asthma. This study aims to determine lower airway hyperresponsiveness (AHR), inflammation and lung function in non-asthmatic patients with NAR. Methods We recruited 262 non-asthmatic patients with NAR, 377 with AR and 264 healthy subjects. All subjects were non-smokers who underwent meticulous history taking, nasal examination, allergen skin prick test (SPT), blood routine test, measurement of fractional exhaled nitric oxide (FeNO), methacholine bronchial challenge test and induced sputum eosinophil count, in this order. Results Compared with healthy subjects, non-asthmatic patients with NAR yielded markedly lower FEV1/FVC, maximal mid-expiratory flow (MMEF), mid-expiratory flow when 50% of FVC has been expired (MEF50%) and mid-expiratory flow when 75% of FVC has been expired (MEF25%) (P<0.05). Differences in spirometry between group AR and NAR were unremarkable (P>0.05). Patients with NAR yielded higher rate of AHR and higher FeNO levels than healthy subjects but lower than those with AR. The proportion of lower airways disorders (sputum eosinophilia, high FeNO levels or AHR) was highest in group AR (70.8%), followed by NAR (53.4%) and healthy subjects (24.2%) (P<0.01). However, sputum eosinophils in NAR patients were not higher compared with healthy subjects (P>0.05). Sputum eosinophils and FeNO had significant correlation with positive AHR and MMEF in group AR but not in NAR. Conclusions Non-asthmatic patients with NAR harbor lower AHR, small airways dysfunction and inflammation, despite being less significant than those with AR. This offers clues to unravel the link between NAR and asthma. PMID:26623098

  15. Multiple bronchoceles in a non-asthmatic patient with allergic bronchopulmonary aspergillosis.

    PubMed

    Amin, Muhammad Umar; Mahmood, Rabia

    2008-09-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction due to a fungus, Aspergillus fumigatus. It is typically seen in patients with long-standing asthma. Our patient was a non-asthmatic 18 years old male who presented with chronic cough for 2 years. Peripheral blood eosinophilia and elevated scrum IgE were observed. His x-ray chest revealed v-shaped opacity in the left upper lobe close to the hilum. High resolution computed tomographic scan of the chest revealed multiple dilated bronchi filled with mucous (bronchoceles) and central bronchiectasis (CB) involving main segmental bronchi. Central bronchiectasis (CB) was typical of ABPA but bronchocele formation was a rare manifestation of the disease. The patient was managed with oral prednisolone and was relieved of his symptoms. Occurrence of ABPA in non-asthmatics is very rare and deserves reporting. PMID:18846804

  16. Bone mineral density in asthmatic patients using low dose inhaled glucocorticosteroids.

    PubMed

    El, O; Gulbahar, S; Ceylan, E; Ergor, G; Sahin, E; Senocak, O; Oncel, S; Cimrin, A

    2005-01-01

    Inhaled glucocorticosteroids are clearly beneficial in subjects with moderate or severe asthma since they are well tolerated, reduce symptoms, and improve quality of life. Some studies suggest that inhaled glucocorticosteroids can adversely affect bone mineral density. The aim of this study is to determine the effects of inhaled glucocorticosteroid therapy on bone mineral density in female patients. Forty-five asthmatic female patients (36 premenopousal and 9 postmenopausal) and forty-six healthy control subjects were included in the study. Bone mineral density was measured from lumbar spine (L1-4) and femur (neck, trochanter, and Ward's triangle) by dual energy X-Ray absorptiometry. Age, occupation, menopause and smoking status, alcohol consumption, body mass index, previous fractures, family history of fractures, menstrual history, ooferectomy, number of pregnancies, the duration of lactation, physical activity and calcium intake were questioned according to the European Vertebral Osteoporosis Study Group (EVOS) form. Cumulative inhaled glucocorticosteroid dose was calculated. T score of femoral neck and T score and bone mineral density of Ward's triangle were significantly lower in asthmatic patients compared to control group but no statistically significant correlation was found between the disease duration, inhaled steroid treatment duration, cumulative inhaled dose and annual inhaled steroid dose and bone mineral density measurement. These results suggest that in asthmatic patients using low dose inhaled corticosteroids bone mineral density is lower than in healthy controls but it is still unclear if asthma by itself is a risk factor for osteoporosis. PMID:15864884

  17. Allergens Induce the Release of Lactoferrin by Neutrophils from Asthmatic Patients

    PubMed Central

    Ventura, Inmaculada; Chamorro, Cristina; Aroca, Rocío; Prados, Manuel; Bobadilla, Pedro; Rodríguez, David; Palacios, Ricardo; Monteseirín, Javier

    2015-01-01

    Background Despite the evidence that Lactoferrin (Lf) is involved in allergic asthma processes, it is unknown whether neutrophils can be one of the main cellular sources of this key inflammatory mediator directly in response of an IgE mediated stimulus. The present study was undertaken to analyze this question. Methods Neutrophils from healthy subjects (n = 34) and neutrophils from allergic asthmatic patients (n = 102) were challenged in vitro with specific allergens to which the patients were sensitized, PAF, or agonist mAbs against IgE-receptors, and the levels of Lf were measured in the culture supernatant. The levels of serum IgE together with the severity of symptoms were also analyzed. Results Lf was released into the culture supernatant of neutrophils from allergic asthmatic patients in response to allergens and PAF. This response was highly allergen-specific, and did not happen in neutrophils from healthy donors. Allergen effect was mimicked by Abs against FcεRI and galectin-3 but not by FcεRII. The levels of released Lf correlated well with the levels of serum specific IgE and severity of asthma symptoms. These observations represent a novel view of neutrophils as an important source of Lf in allergic asthma. Importantly, the levels of released Lf by neutrophils could therefore be used to evaluate disease severity in allergic asthmatic patients. PMID:26488881

  18. [Clinico-functional data concerning chronic asthmatic bronchitis patients treated wih guacetisal].

    PubMed

    Bande, G; Coghe, M; Meloni, M; Nonne, G

    1981-02-28

    Guacetisal was administered to a group of patients suffering from chronic asthmatic bronchitis. The drug in question was shown to possess a good fluidifying, expectorant and indirect anti-cough action, by means of an initial increase of the bronchial secretions and a subsequent progressive decrease of secretions towards the end of the treatment. The analysis of the respiratory parameters examined showed no modifications of statistical significance. PMID:7243036

  19. Impaired P2X1 Receptor-Mediated Adhesion in Eosinophils from Asthmatic Patients.

    PubMed

    Wright, Adam; Mahaut-Smith, Martyn; Symon, Fiona; Sylvius, Nicolas; Ran, Shaun; Bafadhel, Mona; Muessel, Michelle; Bradding, Peter; Wardlaw, Andrew; Vial, Catherine

    2016-06-15

    Eosinophils play an important role in the pathogenesis of asthma and can be activated by extracellular nucleotides released following cell damage or inflammation. For example, increased ATP concentrations were reported in bronchoalveolar lavage fluids of asthmatic patients. Although eosinophils are known to express several subtypes of P2 receptors for extracellular nucleotides, their function and contribution to asthma remain unclear. In this article, we show that transcripts for P2X1, P2X4, and P2X5 receptors were expressed in healthy and asthmatic eosinophils. The P2X receptor agonist α,β-methylene ATP (α,β-meATP; 10 μM) evoked rapidly activating and desensitizing inward currents (peak 18 ± 3 pA/pF at -60 mV) in healthy eosinophils, typical of P2X1 homomeric receptors, which were abolished by the selective P2X1 antagonist NF449 (1 μM) (3 ± 2 pA/pF). α,β-meATP-evoked currents were smaller in eosinophils from asthmatic patients (8 ± 2 versus 27 ± 5 pA/pF for healthy) but were enhanced following treatment with a high concentration of the nucleotidase apyrase (17 ± 5 pA/pF for 10 IU/ml and 11 ± 3 pA/pF for 0.32 IU/ml), indicating that the channels are partially desensitized by extracellular nucleotides. α,β-meATP (10 μM) increased the expression of CD11b activated form in eosinophils from healthy, but not asthmatic, donors (143 ± 21% and 108 ± 11% of control response, respectively). Furthermore, α,β-meATP increased healthy (18 ± 2% compared with control 10 ± 1%) but not asthmatic (13 ± 1% versus 10 ± 0% for control) eosinophil adhesion. Healthy human eosinophils express functional P2X1 receptors whose activation leads to eosinophil αMβ2 integrin-dependent adhesion. P2X1 responses are constitutively reduced in asthmatic compared with healthy eosinophils, probably as the result of an increase in extracellular nucleotide concentration. PMID:27183585

  20. Within-Breath Analysis of Respiratory Mechanics in Asthmatic Patients by Forced Oscillation

    PubMed Central

    Veiga, Juliana; Lopes, Agnaldo José; Jansen, José Manoel; de Melo, Pedro Lopes

    2009-01-01

    INTRODUCTION: The within-breath analysis of respiratory mechanics by the monofrequency Forced Oscillation Technique (mFOT) is of great interest in both physiopathology studies and the diagnosis of respiratory diseases. However, there are limited data on the use of this technique in the analysis of asthma. This study evaluates within-breath mechanics of asthmatic individuals and the contribution of the mFOT in the asthma diagnosis. METHODS: Twenty-two healthy and twenty-two asthmatic subjects, including patients with mild (n=8), moderate (n=8), and severe (n=6) obstruction, were studied. Forced Oscillation Technique data were interpreted using the mean respiratory impedance (Zt), the impedance during inspiration (Zi), expiration (Ze), at the beginning of inspiration (Zii), and at expiration (Zie). The peak-to-peak impedance (Zpp) was also calculated by the subtraction of Zii from Zie. Receiver operating characteristic curves were used to determine the sensitivity (Se) and specificity (Sp) of m Forced Oscillation Technique parameters in identifying asthma. RESULTS: Respiratory impedance values were significantly higher in asthmatics: Zt (p<0.001), Zi (p<0.001), Ze (p<0.001), Zii (p<0.001), Zie (p<0.001), and Zpp (p<0.003). The best parameters for detecting asthma were Zi, Zii, and Zie (Se=90.9%, Sp=90.9%), followed by Zt and Ze. These results are in close agreement with recently published theories and pathophysiological fundamentals. CONCLUSIONS: mFOT permits a non-invasive and detailed analysis in different phases of the respiratory cycle, providing parameters that are adequate for the diagnosis of asthma with high accuracy. These results confirm the high clinical and scientific potential of this methodology in the evaluation of asthmatic patients. PMID:19606241

  1. Psychosocial Context of Differences Between Asthmatic and Diabetic Patients in Adaptation to Disease.

    PubMed

    Wilczyńska, Agnieszka; Sikora, Jagoda; Pituła, Beata

    2016-01-01

    A significant rise in the incidence of asthma and diabetes makes the psychosocial underpinnings of these diseases an increasingly important issue. This article examines differences in psychosocial functioning between healthy people and patients suffering from asthma and diabetes, as separate disease entities. Psychological factors seem to play a significant role particularly in the process of recovery and adaptation to the disease. Our assumption was that a time perspective, a sense of belonging, and a hope may be related to the functioning of people with chronic asthma and diabetes. The study involved a total of 90 people assigned to three groups: healthy individuals, asthmatic patients, and diabetic patients. The findings demonstrate that patients suffering from asthma have a different attitude toward the future and a sense of fatalism in the present. Yet there are no significant differences between asthma patients and healthy individuals in the sense of belonging and hope. Diabetic patients perceive the present as more fatalistic than asthmatic patients and healthy individuals, and they are less oriented at setting and achieving future goals. The finding that the type and course of the disease are associated with specific psychosocial adaptation may have functional and therapeutic implications, and thus should get psycho-clinical attention. PMID:26542598

  2. Lovastatin-induced decrease of intracellular cholesterol level attenuates fibroblast-to-myofibroblast transition in bronchial fibroblasts derived from asthmatic patients.

    PubMed

    Michalik, Marta; Soczek, Ewelina; Kosińska, Milena; Rak, Monika; Wójcik, Katarzyna Anna; Lasota, Sławomir; Pierzchalska, Małgorzata; Czyż, Jarosław; Madeja, Zbigniew

    2013-03-15

    Chronic inflammation of the airways and structural changes in the bronchial wall are basic hallmarks of asthma. Human bronchial fibroblasts derived from patients with diagnosed asthma display in vitro predestination towards TGF-β-induced fibroblast-to-myofibroblast transition (FMT), a key event in the bronchial wall remodelling. Statins inhibit 3-hydroxymethyl-3-glutaryl coenzyme A reductase, a key enzyme in the cholesterol synthesis pathway and are widely used as antilipidemic drugs. The pleiotropic anti-inflammatory effects of statins, independent of their cholesterol-lowering capacity, are also well established. Since commonly used anti-asthmatic drugs do not reverse the structural remodelling of the airways and statins have tentative anti-asthmatic activity, we have studied the effect of lovastatin on FMT in populations of human bronchial fibroblasts derived from asthmatic patients. We demonstrate that the intensity of FMT induced by TGF-β1 was strongly and dose-dependently attenuated by lovastatin. Furthermore, we show that neither the suppression of prenylation of signalling proteins nor the effect on reactive oxygen species formation are important for lovastatin-induced inhibition of myofibroblast differentiation. On the other hand, we show that a squalene synthase inhibitor, zaragozic acid A, reduced the TGF-β1-induced FMT to an extent comparable to lovastatin effect. Additionally we demonstrate that in bronchial fibroblast populations, both inhibitors (lovastatin and zaragozic acid A) attenuate the TGF-β1-induced Smad2 nuclear translocation in a manner dependent on intracellular cholesterol level. Our data suggest that statins can directly, by decrease of intracellular cholesterol level, affect basic cell signalling events crucial for asthmatic processes and potentially prevent perilous bronchial wall remodelling associated with intensive myofibroblast formation. PMID:23485731

  3. Predictors of Asthma Control by Stepwise Treatment in Elderly Asthmatic Patients.

    PubMed

    Ban, Ga-Young; Ye, Young-Min; Lee, Yunhwan; Kim, Jeong-Eun; Nam, Young-Hee; Lee, Soo-Keol; Kim, Joo-Hee; Jung, Ki-Suck; Kim, Sang-Ha; Park, Hae-Sim

    2015-08-01

    The geriatric population is increasing, and asthma severity increases with age. We determined the predictors of asthma control, exacerbation, and the factors that affect asthma-specific quality of life (A-QOL) in elderly asthmatic patients. This was a prospective, multicenter, real-life study for 6 months with stepwise pharmacologic treatment based on the Global Initiative for Asthma (GINA) guideline. A total of 296 asthmatic patients aged ≥ 60 yr were recruited from 5 university centers in Korea. The improved-asthma control group was defined as the group of patients who maintained well-controlled or improved disease and the not-improved asthma control group was defined as the remaining patients. Fewer number of medications for comorbidities (2.8 ± 3.3 in the improved vs. 4.5 ± 4.4 in the control) and higher physical functioning (PF) scale (89.8 ± 14.2 in the improved vs. 82.0 ± 16.4 in the control) were significant predictors in the improved-asthma control group (OR = 0.863, P = 0.004 and OR = 1.028, P = 0.018, respectively). An asthma control test (ACT) score of ≤ 19 at baseline was a significant predictor of asthma exacerbation (OR = 3.938, P = 0.048). Asthma duration (F = 5.656, P = 0.018), ACT score (F = 12.237, P = 0.001) at baseline, and the presence of asthma exacerbation (F = 5.565, P = 0.019) were significant determinants of changes in A-QOL. The number of medications for comorbidities and performance status determined by the PF scale may be important parameters for assessing asthma control in elderly asthmatic patients. PMID:26240480

  4. [Tele-medicine system for high-risk asthmatic patients].

    PubMed

    Kokubu, F; Suzuki, H; Sano, Y; Kihara, N; Adachi, M

    1999-07-01

    We have developed a tele-medicine system to monitor the airway status at home for patients with poorly controlled asthma, whereby a nurse provides instructions to individuals via the telephone to help them manage exacerbation under the supervision of their physicians. We examined the effectiveness of this system with a randomized control study. Patients with high hospitalization risk were enrolled in the study by screening patients for those with multiple previous emergency room visits and randomly assigned to either the tele-medicine or control group. After six months of participation in the program, the number of emergency room visits decreased significantly and the activities of daily living were improved in the tele-medicine group. Most of the patients in the tele-medicine group were able to continue measuring and transmitting peak expiratory flow (PEF) value successfully, and at six months had noticed an improvement in PEF. We therefore conclude that the system effectively contributes to the management of poorly controlled asthma. In addition, further consideration suggests that the reduction of emergency room visits may lead to reduction in hospitalization since we found a good correlation between number of emergency room visits and hospitalization from the studies published previously. PMID:10481354

  5. Cardiovascular side effects of inhaled salbutamol in hypoxic asthmatic patients

    PubMed Central

    Burggraaf, J; Westendorp, R; Veen, J; Schoemaker, R; Sterk, P; Cohen, A; Blauw, G

    2001-01-01

    BACKGROUND—Beta-2 adrenoceptor agonists have been associated with sudden death in asthma patients but the cause and underlying mechanism are unclear. Animal experiments indicate that the combination of hypoxia and β2 agonists may result in detrimental cardiovascular effects. A study was undertaken to investigate the effect of hypoxia on the systemic vascular effects of salbutamol in patients with asthma who are hypoxic by assessing forearm blood flow (FBF) as a measure of peripheral vasodilatation.
METHODS—Eight men with mild asthma underwent the following treatments: normoxia + placebo (NP), normoxia + salbutamol (NS), hypoxia+ placebo (HP), and hypoxia + salbutamol (HS). The period of mask breathing started at t=0 minutes, lasted for 60 minutes, and at 30 minutes 800 µg salbutamol was inhaled. The experiment was completed 30 minutes after the inhalation (t=60 minutes). For the hypoxia treatment the SpO2 level was 82%. Differences between treatments were sought using factorial ANOVA on percentage change from the pretreatment value.
RESULTS—There were no significant differences in blood pressure and potassium levels between the treatments. After 60 minutes the increase in FBF was 13% (95% CI -12 to 39) more for HP treatment than for NP, 21% (95% CI -5 to 46) more for NS than for NP, and 32% (95% CI 7 to 58) more for HS than for HP (p=0.016). The inhalation of salbutamol during hypoxia resulted in a significant increase in FBF of 45% (95% CI 20 to 71) compared with NP (p=0.001).
CONCLUSION—Patients with asthma who are hypoxic and inhale β2 agonists have serious systemic vascular side effects which may be an additional explanation for the association between asthma treatment and sudden death.

 PMID:11413357

  6. Increased tachykinin levels in induced sputum from asthmatic and cough patients with acid reflux

    PubMed Central

    Patterson, Robert N; Johnston, Brian T; Ardill, Joy E S; Heaney, Liam G; McGarvey, Lorcan P A

    2007-01-01

    Background Acid reflux may aggravate airway disease including asthma and chronic cough. One postulated mechanism concerns a vagally‐mediated oesophageal‐tracheobronchial reflex with airway sensory nerve activation and tachykinin release. Aim To test the hypothesis that patients with airways disease and reflux have higher airway tachykinin levels than those without reflux. Methods Thirty‐two patients with airways disease (16 with mild asthma and 16 non‐asthmatic subjects with chronic cough) underwent 24 h oesophageal pH monitoring. Acid reflux was defined as increased total oesophageal acid exposure (% total time pH <4 of >4.9% at the distal probe). All subjects underwent sputum induction. Differential cell counts and concentrations of substance P (SP), neurokinin A (NKA), albumin and α2‐macroglobulin were determined. Results SP and NKA levels were significantly higher in patients with reflux than in those without (SP: 1434 (680) pg/ml vs 906 (593) pg/ml, p = 0.026; NKA: 81 (33) pg/ml vs 52 (36) pg/ml, p = 0.03). Significantly higher tachykinin levels were also found in asthmatic patients with reflux than in asthmatic patients without reflux (SP: 1508 (781) pg/ml vs 737 (512) pg/ml, p = 0.035; NKA: median (interquartile range 108 (85–120) pg/ml vs 75 (2–98) pg/ml, p = 0.02). In patients with asthma there was a significant positive correlation between distal oesophageal acid exposure and SP levels (r = 0.59, p = 0.01) and NKA levels (r = 0.56, p = 0.02). Non‐significant increases in SP and NKA were measured in patients with cough with reflux (SP: 1534.71 (711) pg/ml vs 1089 (606) pg/ml, p = 0.20; NKA: 56 (43) pg/ml vs 49 (17) pg/ml, p = 0.71). No significant difference in differential cell counts or any other biochemical parameter was noted between study groups. Conclusion This study demonstrates increased airway tachykinin levels in patients with asthma and cough patients with

  7. Effect of Hyssopus officinalis L. on inhibiting airway inflammation and immune regulation in a chronic asthmatic mouse model

    PubMed Central

    MA, XIAOJUAN; MA, XIUMIN; MA, ZHIXING; WANG, JING; SUN, ZHAN; YU, WENYAN; LI, FENGSEN; DING, JIANBING

    2014-01-01

    The Uygur herb, Hyssopus officinalis L., has been demonstrated to affect the levels of a number of cytokines in asthmatic mice, including interleukin-4, -6 and -17 and interferon-γ. In the present study, the effect of Hyssopus officinalis L. on airway immune regulation and airway inflammation was investigated in a mouse model of chronic asthma. A total of 32 BALB/c mice were randomly divided into four groups, which included the normal, chronic asthmatic, dexamethasone treatment and Hyssopus officinalis L.treatment groups. Mice were sensitized and challenged with ovalbumin to establish an asthma model and the ratio of eosinophils (EOS) in the bronchoalveolar lavage fluid (BALF) was determined. In addition, the levels of immunoglobulin (Ig)E and IgG were detected using an enzyme-linked immunosorbent assay. The degree of airway mucus secretion was observed using the periodic acid-Schiff stain method. The results demonstrated that the ratio of EOS in the BALF and the level of serum IgE in the chronic asthmatic and dexamethasone treatment groups increased, while the level of serum IgG decreased, when compared with the normal group. In addition, excessive secretion of airway mucus was observed in these two groups. However, the EOS ratio in the BALF and the levels of serum IgE and IgG in the Hyssopus officinalis L. treatment group were similar to the results observed in the normal group. In conclusion, Hyssopus officinalis L. not only plays an anti-inflammatory role by inhibiting the invasion of EOS and decreasing the levels of IgE, but also affects immune regulation. PMID:25289025

  8. Effect of Hyssopus officinalis L. on inhibiting airway inflammation and immune regulation in a chronic asthmatic mouse model.

    PubMed

    Ma, Xiaojuan; Ma, Xiumin; Ma, Zhixing; Wang, Jing; Sun, Zhan; Yu, Wenyan; Li, Fengsen; Ding, Jianbing

    2014-11-01

    The Uygur herb, Hyssopus officinalis L., has been demonstrated to affect the levels of a number of cytokines in asthmatic mice, including interleukin-4, -6 and -17 and interferon-γ. In the present study, the effect of Hyssopus officinalis L. on airway immune regulation and airway inflammation was investigated in a mouse model of chronic asthma. A total of 32 BALB/c mice were randomly divided into four groups, which included the normal, chronic asthmatic, dexamethasone treatment and Hyssopus officinalis L.treatment groups. Mice were sensitized and challenged with ovalbumin to establish an asthma model and the ratio of eosinophils (EOS) in the bronchoalveolar lavage fluid (BALF) was determined. In addition, the levels of immunoglobulin (Ig)E and IgG were detected using an enzyme-linked immunosorbent assay. The degree of airway mucus secretion was observed using the periodic acid-Schiff stain method. The results demonstrated that the ratio of EOS in the BALF and the level of serum IgE in the chronic asthmatic and dexamethasone treatment groups increased, while the level of serum IgG decreased, when compared with the normal group. In addition, excessive secretion of airway mucus was observed in these two groups. However, the EOS ratio in the BALF and the levels of serum IgE and IgG in the Hyssopus officinalis L. treatment group were similar to the results observed in the normal group. In conclusion, Hyssopus officinalis L. not only plays an anti-inflammatory role by inhibiting the invasion of EOS and decreasing the levels of IgE, but also affects immune regulation. PMID:25289025

  9. Priming effect of platelet activating factor on leukotriene C4 from stimulated eosinophils of asthmatic patients.

    PubMed Central

    Shindo, K.; Koide, K.; Hirai, Y.; Sumitomo, M.; Fukumura, M.

    1996-01-01

    BACKGROUND: Eosinophils from asthmatic patients are known to release greater amounts of leukotrienes than normal eosinophils when stimulated by the calcium ionophore A23187. The effect of platelet activating factor (PAF) in priming eosinophils was investigated. METHODS: Eosinophils were obtained from 18 asthmatic patients and 18 healthy donors. Cells separated by the Percoll gradients were incubated with PAF (C-18) for 30 minutes and then stimulated with the calcium ionophore A23187 (2.5 microM) for 15 minutes. The amount of leukotriene C4 (LTC4) in supernatants was measured using a combination of high pressure liquid chromatography and radioimmunoassay. RESULTS: The mean (SD) amount of LTC4 released by eosinophils from asthmatic patients upon stimulation with the calcium ionophore A23187 alone was 27.9 (9.9) ng/10(6) cells (n = 6). The amount of LTC4 released following stimulation with the calcium ionophore A23187 after pretreatment with PAF (1, 5, and 10 microM) was 57.2 (8.9), 75.1 (14.3), and 52.6 (10.7) ng/10(6) cells (n = 6), respectively. Trace amounts of LTC4 (0.9 (0.02) ng/10(6) cells, n = 6) were detected in the supernatant of the cells after stimulation by PAF alone (5 microM). The amount of LTC4 released upon stimulation by calcium ionophore A23187 alone in eosinophils from healthy donors was 10.3 (3.7) ng/10(6) cells (n = 4). The amounts of LTC4 released upon stimulation with calcium ionophore A23187 after pretreatment with PAF at concentrations of 1, 5, and 10 microM were 11.9 (3.5), 17.8 (5.6), and 12.7 (5.1) ng/10(6) cells (n = 4), respectively. Trace amounts of LTC4 (0.6 (0.02) ng/10(6) cells, n = 4) were detected in the supernatant of the cells upon stimulation with PAF alone (5 microM). The amounts of LTC4 released upon stimulation with calcium ionophore A23187 after pretreatment with lyso-PAF at concentrations of 1, 5, and 10 microM (n = 4 or 6) were 30.8 (5.2), 22.9 (5.1), and 27.3 (4.3) ng/10(6) cells (n = 6) from the eosinophils of asthmatic

  10. Increased activity of 5-lipoxygenase in polymorphonuclear leukocytes from asthmatic patients

    SciTech Connect

    Mita, H.; Yui, Y.; Taniguchi, N.; Yasueda, H.; Shida, T.

    1985-09-09

    The formation of 5-lipoxygenase products of arachidonic acid, 5-HETE and 5,12-diHETE, was determined in 100,000 x g supernatant of polymorphonuclear leukocytes from 17 healthy subjects, 17 patients with extrinsic asthma and 15 patients with intrinsic asthma. After the supernatant was incubated with /sup 14/C-arachidonic acid in the presence of calcium and indomethacin, the lipoxygenase products of arachidonic acid were separated by thin layer chromatography. The results were expressed as the percentage conversion of /sup 14/C-arachidonic acid into the product per 10/sup 7/ cells. The formation of 5,12-diHETE, but not of the 5-HETE, was significantly increased in the cells from the group of patients with extrinsic asthma (4.38 +/- 0.78%, mean +/- S.E.; p < 0.01) and intrinsic asthma (6.09 +/- 1.11%; p < 0.01), when compared to normal subjects (1.74 +/- 0.30%). Both extrinsic and intrinsic asthmatics had significantly enhanced 5-lipoxygenase activity, which was expressed as the sum of percentage conversion of /sup 14/C-arachidonic acid into 5-HETE and 5,12-diHETE. The percentage conversion in normal subjects was 4.19 +/- 0.39%, 6.24 +/- 0.84% for 17 patients with extrinsic asthma (p < 0.05), and 8.59 +/- 1.29% for 15 patients with intrinsic asthma (p < 0.01). There was no significant difference between these asthmatic groups. These results indicate that 5-lipoxygenase activity is increased in patients with bronchial asthma. 22 references, 3 figures.

  11. Innate and adaptive T cells in asthmatic patients: Relationship to severity and disease mechanisms

    PubMed Central

    Hinks, Timothy S.C.; Zhou, Xiaoying; Staples, Karl J.; Dimitrov, Borislav D.; Manta, Alexander; Petrossian, Tanya; Lum, Pek Y.; Smith, Caroline G.; Ward, Jon A.; Howarth, Peter H.; Walls, Andrew F.; Gadola, Stephan D.; Djukanović, Ratko

    2015-01-01

    Background Asthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear. Objective We performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients. Methods Sixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed. Results Significant heterogeneity of T-cell phenotypes was observed, with levels of IL-13–secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and γδ-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased mast cell mediator levels in patients with severe asthma both in its atopic (type 2 cytokine–high) and nonatopic forms. Conclusion The evidence for a role for TH17 cells in patients with severe asthma is limited. Severe asthma is associated with a striking deficiency of MAIT cells and high mast cell mediator levels. This study provides proof of concept for disease mechanistic networks in asthmatic patients with clusters that could inform the development of new therapies. PMID:25746968

  12. Asthma problems in southern Italy: A statistical study of 2362 asthmatic patients.

    PubMed

    D'Amato, G; Cocco, G; Melillo, G

    1979-01-01

    In this report we have described the statistical results of a clinical study on 2362 asthmatic patients living mostly in the Naples area and observed in our Division of Respiratory Allergy from January 1976 to May 1978. All data have been analyzed by a computerized method using an Univac 1100 Computer. We have studied some aspects of the atopic syndrome in this population of Southern Italy: frequency of allergic sensitization according to endogenous and extrinsic factors (particularly Parietaria officinalis, a characteristic pollen of the Southern Italian Flora), etc. Finally we have presented the first results of our allergological investigation in Naples concerning the distribution of allergic sensitization according to air pollution of the patient's home. PMID:525607

  13. Correlation of 5-HTT, BDNF and NPSR1 gene polymorphisms with anxiety and depression in asthmatic patients

    PubMed Central

    YANG, YUAN; ZHAO, MINGZHE; ZHANG, YUQUN; SHEN, XINHUA; YUAN, YONGGUI

    2016-01-01

    Asthmatic patients are known to have a higher risk of anxiety and depression. In the present study, we aimed to explore the association of serotonin transporter (5-HTT), brain-derived neurotrophic factor (BDNF) and neuropeptide S receptor 1 (NPSR1) gene polymorphisms with anxiety and depression in asthmatic patients. This was a cross-sectional study conducted on 143 asthmatic patients and 175 healthy volunteers. Of the asthmatic patients, 49 suffered from anxiety and 12 exhibited signs of depression. Patients with a lower level of education were more prone to depression. Both anxiety and depression were associated with poor asthma control as evaluated by the Asthma Control Test (ACT) score. The association of single nucleotide polymorphisms of BDNF, NPSR1 and 5-HTT with anxiety and depression in asthamtic patients was evaluated. The distribution of 5-HTT gene polymorphisms in the healthy group, the group with asthma but without anxiety, and the group with asthma and anxiety had significant differences. Females with asthma and anxiety were more prone to BDNF polymorphism. Also, BDNF gene distribution exhibited significant differences among those in the healthy group, the group with asthma but no depression, and the group with asthma and depression; however, NPSR1 gene distribution did not vary greatly between the groups. The anxiety score was significantly affected by the interaction between 5-HTT (LL, S+) and BDNF (A+, GG) (H=5.99, P=0.015). The depression score was significantly affected by the interaction between BDNF (A+, GG) and NPSR1 (AA, T+). We noted that both anxiety and depression led to poor asthma control. The interaction between 5-HTT (LL) and BDNF (A+) increased the risk of anxiety, and the interaction between BDNF (A+, GG) and NPSR1 (AA, T+) increased the risk of depression in asthmatic patients. PMID:27176146

  14. Citric acid cough threshold and airway responsiveness in asthmatic patients and smokers with chronic airflow obstruction.

    PubMed Central

    Auffarth, B; de Monchy, J G; van der Mark, T W; Postma, D S; Koëter, G H

    1991-01-01

    The relation between citric acid cough threshold and airway hyperresponsiveness was investigated in 11 non-smoking patients with allergic asthma (mean FEV1 94% predicted) and 25 non-atopic smokers with chronic airflow obstruction (mean FEV1 65% predicted). Cough threshold was determined on two occasions by administering doubling concentrations of citric acid. Seven of the 11 asthmatic subjects and 14 of 25 smokers with chronic airflow obstruction had a positive cough threshold on both test days. Cough threshold measurements were reproducible in both groups (standard deviation of duplicate measurements 1.2 doubling concentrations in asthma, 1.1 doubling concentrations in chronic airflow obstruction). Citric acid provocation did not cause bronchial obstruction in most patients, though four patients had a fall in FEV1 of more than 20% for a short time on one occasion only. No significant difference in cough threshold was found between the two patient groups despite differences in baseline FEV1 values. There was no significant correlation between cough threshold and the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) histamine in either group. Thus sensory nerves can be activated with a tussive agent in patients with asthma and chronic airflow obstruction without causing bronchial smooth muscle contraction. PMID:1948792

  15. Levodropropizine (LD) activity in allergic asthmatic patients, challenged with ultrasonically nebulized distilled water, metacholine and allergen-induced bronchospasm.

    PubMed

    Bossi, R; Banfi, P; Filipazzi, V; Castelli, C; Braga, P C

    1994-04-01

    The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p < or = 0.05] in comparison to no effect for placebo. Similarly, in airway responsiveness to specific allergen, active treatment antagonized the bronchoconstrictor effect of grass pollen by 83% and of various allergens (dermatophagoides and grass pollen) by 72%, i.e. AR of 0.17 (95% confidence interval 0.045-0.65; p < 0.01) and of 0.28 (95% confidence interval 0.07-1.04; p < 0.05), respectively. No antagonist effect was evident with placebo at all times. Besides inhibiting cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release. PMID:10184318

  16. Metabolic and ventilatory changes in asthmatic patients during and after exercise

    PubMed Central

    Anderson, Sandra D.; Silverman, M.; Walker, S. R.

    1972-01-01

    Five asthmatic patients aged 25-30 years were studied during and after 6-8 minutes of steady exercise on both a bicycle ergometer and a treadmill. For each patient the duration of work, oxygen consumption, minute ventilation, and heart rate were similar in each form of exercise. During exercise all patients had an increase in peak expiratory flow rate. The blood lactate level was higher during bicycle exercise but arterial Pco2 and pH fell to similar levels during both forms of exercise. There was a rise in arterial oxygen tension in four of the patients during exercise; in one subject arterial oxygen tension fell. Bronchoconstriction was greater following treadmill exercise in all subjects and was associated with an increase in ventilation/perfusion inequality, as shown by arterial hypoxaemia, an increase in alveolar-arterial oxygen tension gradients, and an increase in physiological dead space. In one subject whose PEFR fell to 25% of the predicted value Co2 retention occurred. These changes are similar to those found in other forms of acute asthma. In one subject, during both forms of exercise the mixed expired Pco2 was observed to be higher than the arterial Pco2, thus giving a negative value for physiological dead space. This observation is discussed. PMID:4647631

  17. Medicinal herb use among asthmatic patients attending a specialty care facility in Trinidad

    PubMed Central

    Clement, Yuri N; Williams, Arlene F; Aranda, Derick; Chase, Ronald; Watson, Nadya; Mohammed, Rochelle; Stubbs, Odia; Williamson, Deneil

    2005-01-01

    Background There is an increasing prevalence of asthma in the Caribbean and patients remain non-compliant to therapy despite the development of guidelines for management and prevention. Some patients may self-medicate with medicinal herbs for symptomatic relief, as there is a long tradition of use for a variety of ailments. The study assessed the prevalence of use and the factors affecting the decision to use herbs in asthmatic patients attending a public specialty care clinic in Trinidad. Methods A descriptive, cross-sectional study was conducted at the Chest Clinic in Trinidad using a de novo, pilot-tested, researcher-administered questionnaire between June and July 2003. Results Fifty-eight out of 191 patients (30.4%) reported using herbal remedies for symptomatic relief. Gender, age, ethnicity, and asthma severity did not influence the decision to use herbs; however, 62.5% of patients with tertiary level schooling used herbs, p = 0.025. Thirty-four of these 58 patients (58.6%) obtained herbs from their backyards or the supermarket; only 14 patients (24.1%) obtained herbs from an herbalist, herbal shop or pharmacy. Relatives and friends were the sole source of information for most patients (70.7%), and only 10.3% consulted an herbalist. Ginger, garlic, aloes, shandileer, wild onion, pepper and black sage were the most commonly used herbs. Conclusions Among patients attending the Chest Clinic in Trinidad the use of herbal remedies in asthma is relatively common on the advice of relatives and friends. It is therefore becoming imperative for healthcare providers to become more knowledgeable on this modality and to keep abreast with the latest developments. PMID:15713232

  18. Evaluation of Proper Usage of Glucocorticosteroid Inhalers and Their Adverse Effects in Asthmatic Patients

    PubMed Central

    Hejazi, Mohammad Esmayil; Shafiifar, Afsaneh; Mashayekhi, Siminozar

    2016-01-01

    Background: The frequent use of corticosteroid inhalers (CSIs), especially at higher doses, has been accompanied by concern about both systemic and local adverse reactions. The local adverse reactions of inhaled corticosteroids (ICSs) are considered to constitute infrequent and minor problems. However, while not usually serious, these local adverse reactions are of clinical importance. This study assessed the prevalence of local adverse reactions, their clinical features, role of inhaler devices and current measures that have been suggested to prevent the problem. Materials and Methods: This study was performed in YAS clinic in Tabriz on 500 asthmatic patients. A questionnaire about the patients’ demographic information, methods of using CSIs, local care after using CSIs, using spacer devices, doses of ICSs, and adverse reactions were filled then the patients were clinically examined for local adverse reactions. Results: Only 56% patients were using CSIs properly. In general, the incidence of complications was: oropharyngeal candidiasis 25.6%, laryngeal weakness 8.8%, choking 17.6%, tooth decay 15.2%, speechlessness 36.2%, taste decrease 20.8%, tongue burning 29.8% and tongue abrasion 27.8%. Conclusion: Persistent asthma can be effectively controlled with currently available CSIs. Although not life-threatening, local adverse reactions of ICSs are clinically significant and warrant attention. Use of spacer devices and changes in CSI usage, dosage amount and frequency and rinsing and gargling are the methods that have been used to reduce the incidence of local adverse reactions. PMID:27403173

  19. An analysis of skin prick test reactions in 656 asthmatic patients.

    PubMed

    Hendrick, D J; Davies, R J; D'Souza, M F; Pepys, J

    1975-02-01

    Of 656 asthmatic patients referred specifically for allergy assessments, 544 (84 percent) gave positive immediate skin prick tests to at least one of 22 common allergens used routinely. Comparison of these skin test positive patients with the 102 (16 percent) who were skin test negative showed a number of significant differences. The majority of the skin test positive patients (52 percent) were less than 10 years old at the time of onset of the asthma, whereas, of the skin test negative patients, 56 percent were aged over 30 years at the time of onset. Seventy per cent report rhinitis compared with 48 per cent of the skin test negative patients, and 29 per cent reported infantile eczema compared with 9 per cent. Symptoms attributed to house dust, pollens, and animals were noted two to three times more frequently by the skin test positive patients, while corticosteroid drugs had been used more commonly by the skin test negative patients (45 percent compared with 35 percent). No significant differences were observed with the other factors studied, namely, history of urticaria or angio-oedema, family history of "allergic" disease, and awareness of sensitivity to foods, aspirin or penicillin. Prick test reactions in the skin test positive patients were most commonly seen to house dust or the acarine mite, Dermatophagoides farinae (82 percent), followed by pollens (66 percent), animal danders (38 percent), foods (16 percent), Aspergillus fumigatus (16 percent), and other moulds (21 percent). There was a highly significant association of positive history with positive prick test for all allergens studied. PMID:1168378

  20. Acoustic Analysis of Inhaler Sounds From Community-Dwelling Asthmatic Patients for Automatic Assessment of Adherence

    PubMed Central

    D'arcy, Shona; Costello, Richard W.

    2014-01-01

    Inhalers are devices which deliver medication to the airways in the treatment of chronic respiratory diseases. When used correctly inhalers relieve and improve patients' symptoms. However, adherence to inhaler medication has been demonstrated to be poor, leading to reduced clinical outcomes, wasted medication, and higher healthcare costs. There is a clinical need for a system that can accurately monitor inhaler adherence as currently no method exists to evaluate how patients use their inhalers between clinic visits. This paper presents a method of automatically evaluating inhaler adherence through acoustic analysis of inhaler sounds. An acoustic monitoring device was employed to record the sounds patients produce while using a Diskus dry powder inhaler, in addition to the time and date patients use the inhaler. An algorithm was designed and developed to automatically detect inhaler events from the audio signals and provide feedback regarding patient adherence. The algorithm was evaluated on 407 audio files obtained from 12 community dwelling asthmatic patients. Results of the automatic classification were compared against two expert human raters. For patient data for whom the human raters Cohen's kappa agreement score was \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${>}{0.81}$\\end{document}, results indicated that the algorithm's accuracy was 83% in determining the correct inhaler technique score compared with the raters. This paper has several clinical implications as it demonstrates the feasibility of using acoustics to objectively monitor patient inhaler adherence and provide real-time personalized medical care for a chronic respiratory illness. PMID:27170883

  1. An analysis of skin prick test reactions in 656 asthmatic patients.

    PubMed Central

    Hendrick, D J; Davies, R J; D'Souza, M F; Pepys, J

    1975-01-01

    Of 656 asthmatic patients referred specifically for allergy assessments, 544 (84 percent) gave positive immediate skin prick tests to at least one of 22 common allergens used routinely. Comparison of these skin test positive patients with the 102 (16 percent) who were skin test negative showed a number of significant differences. The majority of the skin test positive patients (52 percent) were less than 10 years old at the time of onset of the asthma, whereas, of the skin test negative patients, 56 percent were aged over 30 years at the time of onset. Seventy per cent report rhinitis compared with 48 per cent of the skin test negative patients, and 29 per cent reported infantile eczema compared with 9 per cent. Symptoms attributed to house dust, pollens, and animals were noted two to three times more frequently by the skin test positive patients, while corticosteroid drugs had been used more commonly by the skin test negative patients (45 percent compared with 35 percent). No significant differences were observed with the other factors studied, namely, history of urticaria or angio-oedema, family history of "allergic" disease, and awareness of sensitivity to foods, aspirin or penicillin. Prick test reactions in the skin test positive patients were most commonly seen to house dust or the acarine mite, Dermatophagoides farinae (82 percent), followed by pollens (66 percent), animal danders (38 percent), foods (16 percent), Aspergillus fumigatus (16 percent), and other moulds (21 percent). There was a highly significant association of positive history with positive prick test for all allergens studied. Images PMID:1168378

  2. Effect of hydrocortisone treatment on oxygen metabolism and phagocytosis of peripheral blood neutrophils in asthmatic patients, sensitive and resistant to glucocorticosteroid therapy.

    PubMed

    Jankowska, R; Zak-Nejmark, T; Małolepszy, J; Nadobna, G; Osos, M; Medrala, W

    1994-01-01

    The inflammatory activity of peripheral blood neutrophils of patients suffering from atopic asthma and treated with glucocorticosteroids was investigated. Two tests were performed: 1. chemiluminescence test of neutrophils, and 2. phagocytosis test of latex and bacteria (Staphylococcus aureus 209 P) by neutrophils before and after incubation of the cells with hydrocortisone. The tests were carried out in 3 selected groups of (1) asthmatic steroid sensitive patients, (2) asthmatic steroid resistant patients, and (3) healthy individuals. The neutrophil chemiluminescence stimulation index was found to be significantly lower in the asthmatic steroid sensitive group as compared to the other groups. The index increased in this group after neutrophil incubation with hydrocortisone. The results of phagocytosis of latex by neutrophils before and after their incubation with hydrocortisone were similar in all the 3 groups. The results of phagocytosis of bacteria by neutrophils in the asthmatic steroid sensitive group were significantly lower after incubation of neutrophils with hydrocortisone only. PMID:8572896

  3. Small airway dysfunction by impulse oscillometry in asthmatic patients with normal forced expiratory volume in the 1st second values.

    PubMed

    Pisi, Roberta; Tzani, Panagiota; Aiello, Marina; Martinelli, Enrico; Marangio, Emilio; Nicolini, Gabriele; Olivieri, Dario; Chetta, Alfredo

    2013-01-01

    Small airways are relevant to the pathophysiology of asthma. We investigated whether in asthmatic patients with normal forced expiratory volume in the 1st second (FEV(1)) values, impulse oscillometry system (IOS), as a measure of small airway function, contributed additional information to spirometry either at baseline or after bronchodilator, and whether it was related to the disease control. The fall in resistance from 5 to 20 Hz (R5-R20) and reactance at 5 Hz (X5) by IOS and spirometry measures of small airway function (forced expiratory flow at 25-75% [FEF(25-75)] and forced vital capacity/slow inspiratory vital capacity [FVC/SVC]) at baseline and after 400 micrograms of salbutamol were prospectively measured in 33 asthmatic patients (18 women; age range, 18-66 years). Disease control was assessed by the Asthma Control Test (ACT). R5-R20 but not X5 values were significantly related to FEF(25-75) and FVC/SVC values (p < 0.05 for both correlations). When the bronchodilator response was assessed, no correlation was found among IOS and spirometry changes. ACT scores were related to R5-R20, FEF(25-75), and FVC/SVC values (p < 0.01 for all correlations). In asthmatic patients with normal FEV(1) values, R5-R20 values were related to spirometry measures of small airway function. However, when the bronchodilator response was assessed, IOS and spirometry provided quite different results. Moreover, small airway dysfunction, as assessed by IOS and spirometry, was associated with poor disease control and history of asthma exacerbations. The results of this study confirm the value of IOS, as an investigative tool, and suggest that in asthmatic patients with normal FEV(1) values and poor disease control, small airway function should be investigated. PMID:23406931

  4. Effect of Inhaled Budesonide on Interleukin-4 and Interleukin-6 in Exhaled Breath Condensate of Asthmatic Patients

    PubMed Central

    Chi, Chun-Hua; Liao, Ji-Ping; Zhao, Yan-Ni; Li, Xue-Ying; Wang, Guang-Fa

    2016-01-01

    Background: Studies of interleukin (IL)-4 and IL-6 in the exhaled breath condensate (EBC) of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid (ICS) treatment on IL-4 and IL-6 in the EBC of asthmatic patients. Methods: In a prospective, open-label study, budesonide 200 μg twice daily by dry powder inhaler was administered to 23 adult patients with uncontrolled asthma (mean age 42.7 years) for 12 weeks. Changes in asthma scores, lung function parameters (forced expiratory volume in 1 s [FEV1], peak expiratory flow [PEF], forced expiratory flow at 50% of forced vital capacity [FEF50], forced expiratory flow at 75% of forced vital capacity, maximum mid-expiratory flow rate) and the concentrations of IL-4 and IL-6 in EBC were measured. Results: Both asthma scores and lung function parameters were significantly improved by ICS treatment. The mean IL-4 concentration in the EBC was decreased gradually, from 1.92 ± 0.56 pmol/L before treatment to 1.60 ± 0.36 pmol/L after 8 weeks of treatment (P < 0.05) and 1.54 ± 0.81 pmol/L after 12 weeks of treatment (P < 0.01). However, the IL-6 concentration was not significantly decreased. The change in the IL-4 concentration was correlated with improvements in mean FEV1, PEF and FEF50 values (correlation coefficients −0.468, −0.478, and −0.426, respectively). Conclusions: The concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics. PMID:26996478

  5. Attitudes of Hungarian asthmatic and COPD patients affecting disease control: empirical research based on Health Belief Model

    PubMed Central

    Simon, Judit

    2013-01-01

    Introduction: Patient non-adherence to treatment is a major problem across most chronic diseases. In COPD and asthma treatments it is a complex issue because people need to make behavioral and lifestyle changes while taking medications. Poor adherence results in increased rates of morbidity and mortality, more frequent hospitalizations, and ultimately higher healthcare expenditures. Materials and methods: The objective of the study was to assess asthmatic and COPD patient's attitudes toward adherence in Hungary. Health Belief Model was used to help explain reasons of non-adherence. The results of the study should provide additional support to understanding health-related behaviors and to developing health related programs enhancing adherence of asthmatic and COPD patients. 145 diagnosed COPD patients and 161 diagnosed asthmatic patients were involved in 6 pulmonary centers. The questions were designed to measure Health Belief Model dimensions A 1–5 point verbal Likert scale was used. As a second stage, the answers were compared with the registered patient's personal health data available in pulmonary center's documentation. The data was analyzed using SPSS software. Results: More than 32% of patients are very interested in new asthma or COPD research results, but their main information source is physician. The trust toward the physician is very high. Patients accept treatments and rarely ask questions. Respondents are cooperative but sometimes fail to follow therapeutic recommendations. There is no willingness to join self-help groups or associations. Discussion: The paternalistic approach was generally accepted, moreover expected by the patients from the physicians. It is important to train patients, increase their self-efficacy, responsibility and involve them into self-management programs. Both physicians and patients should be trained how to communicate—this approach can lead to increased understanding and better adherence. PMID:24312052

  6. Effect of carbocysteine on cough reflex to capsaicin in asthmatic patients

    PubMed Central

    Ishiura, Yoshihisa; Fujimura, Masaki; Yamamori, Chihiro; Nobata, Kouichi; Myou, Shigeharu; Kurashima, Kazuyoshi; Michishita, Yasukatsu; Takegoshi, Tadayoshi

    2003-01-01

    Aims Cough, one of the main symptoms of bronchial asthma, is a chronic airway inflammatory disease with functionally damaged bronchial epithelium. Recently, we established an animal model with cough hypersensitivity after antigen challenge and clearly showed the protective effect of carbocysteine in this model. This study was designed to investigate the clinical effect of carbocysteine for cough sensitivity in patients with bronchial asthma. Methods The effects of the two orally active mucoregulatory drugs, carbocysteine and ambroxol hydrochloride, on cough response to inhaled capsaicin were examined in 14 patients with stable asthma. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough sensitivity. Results Geometric mean values of the cough threshold at run-in (baseline) and after 4 weeks’ treatment of placebo, 1500 mg day−1 of carbocysteine and 45 mg day−1 of ambroxol hydrochloride were 12.8 µM (95% confidence interval [CI] 5.5, 29.6), 11.0 µM (95% CI 4.4, 27.5), 21.0 µM (95% CI 8.8, 50.2) and 11.6 µM (95% CI 5.8, 23.3), respectively. The cough threshold for carbocysteine was significantly greater than those of ambroxol hydrochloride (P = 0.047) and placebo (P = 0.047), respectively. Conclusions These findings indicate that carbocysteine administration may be a novel therapeutic option for asthmatic patients, especially with cough variant asthma. PMID:12814442

  7. D prostanoid receptor 2 (chemoattractant receptor–homologous molecule expressed on TH2 cells) protein expression in asthmatic patients and its effects on bronchial epithelial cells

    PubMed Central

    Stinson, Sally E.; Amrani, Yassine; Brightling, Christopher E.

    2015-01-01

    Background The D prostanoid receptor 2 (DP2; also known as chemoattractant receptor–homologous molecule expressed on TH2 cells) is implicated in the pathogenesis of asthma, but its expression within bronchial biopsy specimens is unknown. Objectives We sought to investigate the bronchial submucosal DP2 expression in asthmatic patients and healthy control subjects and to explore its functional role in epithelial cells. Methods DP2 protein expression was assessed in bronchial biopsy specimens from asthmatic patients (n = 22) and healthy control subjects (n = 10) by using immunohistochemistry and in primary epithelial cells by using flow cytometry, immunofluorescence, and quantitative RT-PCR. The effects of the selective DP2 agonist 13, 14-dihydro-15-keto prostaglandin D2 on epithelial cell migration and differentiation were determined. Results Numbers of submucosal DP2+ cells were increased in asthmatic patients compared with those in healthy control subjects (mean [SEM]: 78 [5] vs 22 [3]/mm2 submucosa, P < .001). The bronchial epithelium expressed DP2, but its expression was decreased in asthmatic patients compared with that seen in healthy control subjects (mean [SEM]: 21 [3] vs 72 [11]/10 mm2 epithelial area, P = .001), with similar differences observed in vitro by primary epithelial cells. Squamous metaplasia of the bronchial epithelium was increased in asthmatic patients and related to decreased DP2 expression (rs = 0.69, P < .001). 13, 14-Dihydro-15-keto prostaglandin D2 promoted epithelial cell migration and at air-liquid interface cultures increased the number of MUC5AC+ and involucrin-positive cells, which were blocked with the DP2-selective antagonist AZD6430. Conclusions DP2 is expressed by the bronchial epithelium, and its activation drives epithelial differentiation, suggesting that in addition to its well-characterized role in inflammatory cell migration, DP2 might contribute to airway remodeling in asthmatic patients. PMID:25312757

  8. Eicosanoid Mediators in the Airway Inflammation of Asthmatic Patients: What is New?

    PubMed

    Sanak, Marek

    2016-11-01

    Lipid mediators contribute to inflammation providing both pro-inflammatory signals and terminating the inflammatory process by activation of macrophages. Among the most significant biologically lipid mediators, these are produced by free-radical or enzymatic oxygenation of arachidonic acid named "eicosanoids". There were some novel eicosanoids identified within the last decade, and many of them are measurable in clinical samples by affordable chromatography-mass spectrometry equipment or sensitive immunoassays. In this review, we present some recent advances in understanding of the signaling by eicosanoid mediators during asthmatic airway inflammation. Eicosanoid profiling in the exhaled breath condensate, induced sputum, or their metabolites measurements in urine is complementary to the cellular phenotyping of asthmatic inflammation. Special attention is paid to aspirin-exacerbated respiratory disease, a phenotype of asthma manifested by the most profound changes in the profile of eicosanoids produced. A hallmark of this type of asthma with hypersensitivity to non-steroid anti-inflammatory drugs (NSAIDs) is to increase biosynthesis of cysteinyl leukotrienes on the systemic level. It depends on transcellular biosynthesis of leukotriene C₄ by platelets that adhere to granulocytes releasing leukotriene A₄. However, other abnormalities are also reported in this type of asthma as a resistance to anti-inflammatory activity of prostaglandin E₂ or a robust eosinophil interferon-γ response resulting in cysteinyl leukotrienes production. A novel mechanism is also discussed in which an isoprostane structurally related to prostaglandin E₂ is released into exhaled breath condensate during a provoked asthmatic attack. However, it is concluded that any single eicosanoid or even their complex profile can hardly provide a thorough explanation for the mechanism of asthmatic inflammation. PMID:27582398

  9. Step-down therapy in well-controlled asthmatic patients using salmeterol xinafoate/fluticasone propionate combination therapy

    PubMed Central

    Horiuchi, Kazuya; Kasahara, Keita; Kuroda, Yusuke; Morohoshi, Haruna; Hagiwara, Yosuke; Ishii, Gen

    2016-01-01

    Purpose A combination therapy with inhaled corticosteroid (ICS) and a long-acting β agonist (LABA) is the standard treatment for asthmatic patients, and step-down treatment is recommended once control has been achieved. However, little data exist that evaluate the long-term outcomes after step-down treatment. Objective To compare the long-term outcomes of step-down therapy with ICS/LABA or ICS alone for asthmatic patients who have achieved well-controlled asthma by the ICS (250 µg fluticasone)/LABA (50 µg salmeterol) combination (SFC, two puffs per day). Patients and methods We randomized 40 well-controlled patients with asthma receiving SFC (250 µg) to two groups; one group of patients received step-down therapy with low-dose SFC (100 µg, two puffs daily) and another group of patients received step-down therapy with high-dose fluticasone propionate (FP) alone (500 µg, daily). The two groups were monitored over 12 months for changes in asthma control test scores, respiratory function (percent forced expiratory volume in 1 second, maximal expiratory flow rate at 50% of the vital capacity [%FEF50], and maximal expiratory flow rate at 25% of the vital capacity [%FEF25]), and the concentration of fractional exhaled nitric oxide. Results There was no significant difference in the dropout rate between the SFC and FP groups. Low-dose SFC maintained the stability of all parameters over 12 months, whereas the FP group exhibited a rapid 5% decrease in forced expiratory volume in 1 second within 2 months after discontinuation of salmeterol; furthermore, after 10 months, there was a gradual decrease in %FEF50 and %FEF25. Conclusion This study suggests that a balanced step-down protocol, including both ICS and LABA, is essential in providing long-term stability to patients with mild-to-moderate well-controlled asthma. PMID:27051309

  10. [Induced sputum supernatant prostaglandin E2 during oral aspirin challenge of asthmatic patients with and without aspirin hypersensitivity and healthy controls--pilot study].

    PubMed

    Ignacak, Maria; Celejewska-Wójcik, Natalia; Wójcik, Krzysztof; Sałapa, Kinga; Konduracka, Ewa; Sanak, Marek; Tyrak, Katarzyna; Sładek, Krzysztof; Musiał, Jacek; Mastalerz, Lucyna

    2016-01-01

    The aim of this pilot study was to evaluate changes in the concentration of prostaglandin E2 (PGE2) in induced sputum supernatant in 3 groups: sub- jects with NSAID-exacerbated respira- tory disease (NERD), aspirin tolerant asthma (ATA) and healthy controls (HC), before and after oral aspirin chal- lenge test. The study was conducted in the years 2014-2015 at the Clinical Department of the Pulmonology Clinic at the University Hospital in Cracow. 43 patients were enrolled in the study (NERD - n = 15, ATA - n = 15 and HC - n = 13). All of them underwent a placebo-controlled oral aspirin challenge. Sputum was induced 24 hours before the challenge and immediately after the test. Induced sputum was processed in order to obtain cystospin slides to depict inflammatory cell patterns and supernatants, in which PGE2 was measured. The concentration of PGE2 was determined using mass spectrometry coupled with gas chromatography (gas chromatography/mass spectrometry - GC/MS). After aspirin challenge, the concentration of PGE2 in induced sputum supernatant decreased in both asthmatics hypersensitive to aspirin (p = 0.01) and those who tolerated aspirin well (p = 0.17). The change in the healthy control group was not statistically significant. These results support the cyclooxygenase theory of PGE2 inhibition by aspirin. However, the mechanism of bronchoconstriction after aspirin administration alone in patients with NSAID-exacerbated respiratory disease remains unclear. PMID:27197430

  11. Effect of loratadine, an H1 antihistamine, on induced cough in non-asthmatic patients with chronic cough.

    PubMed Central

    Tanaka, S.; Hirata, K.; Kurihara, N.; Yoshikawa, J.; Takeda, T.

    1996-01-01

    BACKGROUND: H1 antihistamines have been shown to have an antitussive effect in patients with asthma, postnasal drip, and allergic rhinitis. No study has been performed to determine whether orally administered H1 antihistamines can reduce the number of coughs induced by stimulation of cough receptors in non-asthmatic patients with chronic dry cough. METHODS: The effect of loratadine (10 mg) on the number of coughs induced by ultrasonically nebulised distilled water (UNDW) was examined in 10 patients with nasal disease and in seven patients with unexplained chronic cough using a randomised, double blind crossover method. Eleven normal volunteers were also studied. Each subject inhaled UNDW for one minute, and the numbers of coughs during the one minute inhalation and the 30 seconds following it were counted. RESULTS: There was no difference in the results of pulmonary function tests performed before and one minute after UNDW inhalation for either patients or normal subjects. There was also no significant difference between the results of pulmonary function tests before or after oral administration of loratadine. Loratadine significantly reduced the number of coughs in patients with nasal disease and in those with unexplained chronic cough, but not in normal subjects. CONCLUSIONS: The H1 antihistamine loratadine reduces cough induced by UNDW. The release of histamine may contribute to the chronic cough in patients with unexplained chronic cough or nasal disease. Images PMID:8795669

  12. Human mesenchymal stem cells elevate CD4+CD25+CD127low/- regulatory T cells of asthmatic patients via heme oxygenase-1.

    PubMed

    Li, Jian-guo; Zhuan-sun, Yong-xun; Wen, Bing; Wu, Hao; Huang, Feng-ting; Ghimire, Hridaya bibhu; Ran, Pi-xin

    2013-09-01

    Up-regulation of CD4+CD25+CD127low/- regulatory T cells (Tregs) is a new target in the treatment of asthma. Human bone marrow mesenchymal stem cells can up-regulate CD4+CD25+CD127low/- regulatory T cells in vitro, meanwhile, heme oxygenase-1 (HO-1) plays an important role in the development and maintenance of CD4+CD25+ regulatory T cells. However the mechanism has not yet been adequately understood. Hence, we wondered what effect of Heme Oxygenase-1 made on regulation of CD4+CD25+CD127low/- regulatory T cells mediated by mesenchymal stem cells. Peripheral blood mononuclear cells isolated from asthmatic patients and healthy controls were co-cultured with human bone marrow mesenchymal stem cells which were pretreated with Hemin (the revulsive of Heme Oxygenase-1), Protoporphyrin Ⅸ zinc (the inhibitor of Heme Oxygenase-1) and saline. The expression of Heme Oxygenase-1 in MSCs was enhanced by Hemin and inhibited by Protoporphyrin  zinc in vitro. Overexpression of Heme Oxygenase-1 elevated the proportion of CD4+CD25+CD127low/- regulatory T cells in CD4+ T cells, meanwhile, inhibition of Heme Oxygenase-1 decreased the proportion of CD4+CD25+CD127low/- regulatory T cells in CD4+ T cells as compared with mesenchymal stem cells alone. Taken together, these data demonstrated that Heme Oxygenase-1 contributed to the up-regulation of CD4+CD25+CD127low/- regulatory T cells mediated by mesenchymal stem cells in asthma.  PMID:23893806

  13. Identification and association of relationships between selected personal and environmental factors and formal components of temperament and strategies of coping with stress in asthmatic patients.

    PubMed

    Panek, Michał; Pietras, Tadeusz; Witusik, Andrzej; Wieteska, Łukasz; Małachowska, Beata; Mokros, Łukasz; Fendler, Wojciech; Szemraj, Janusz; Kuna, Piotr

    2015-10-01

    Background: Personal and environmental factors might have an impact on strategies of coping with stress and temperamental traits according to the Regulative Theory of Temperament in asthmatic patients. They can modify the clinical picture, the course of a disease and effectiveness of treatment. Personal variables are key factors in determining formal characteristic of behavior and effective management method in asthmatic patients. Aim of study: The aim of the study was to identify selected personal and environmental factors, as well as factors inducing attacks and asthma exacerbations or maintaining them in a complex of personal traits of patients. Methods: Two hundred and eighty one participants were included in the study. Of this number 122 subjects were healthy volunteers and 159 were asthmatic patients. In all the subjects the authors applied the Formal Characteristic of Behaviour – FCZ-KT – Temperament Inventory, Coping Inventory for Stressful Situations (CISS), Beck Depression Inventory, State-Trait Anxiety Inventory and Borg Rating of Perceived Exertion (RPE) Scale. Genotyping of polymorphic forms of NR3C1 gene was conducted with PCR-RFLP and PCR-HRM methods. Expression of TGFβ1 gene was measured with the use of qRT-PCR. Results: The authors confirmed a significant influence of personal and environmental factors, such as: age, height, body weight, sex, asthma exacerbations, drugs administered by patients, allergy and psychopathological variables on strategies of coping with stress by asthmatic patients (Task-Oriented Coping, Emotion-Oriented Coping, Avoidance-Oriented Coping, distraction seeking, social diversion). Temperamental traits (Briskness, Perseverance, Sensory Sensitivity, Emotional Reactivity, Endurance, Activity) depend on age, sex, body weight, genetic predispositions and they are modified by asthma exacerbations, allergy, drugs administered by patients, depression and anxiety (state and trait). The authors confirmed a correlation between

  14. Lack of Association between Toll Like Receptor-2 and Toll Like Receptor-4 Gene Polymorphisms and Other Feature in Iranian Asthmatics Patients.

    PubMed

    Bahrami, Hamid; Daneshmandi, Saeed; Heidarnazhad, Hasan; Pourfathollah, Ali Akbar

    2015-02-01

    Asthma as a chronic inflammatory airway disease is considered to be the most common chronic disease that is involving genetic and environmental factors. Toll like receptors (TLRs) and other inflammatory mediators are important in modulation of inflammation. In this study, we evaluated the role of TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms in the asthma susceptibility, progress, control levels and lung functions in Iranian patients. On 99 asthmatic patients and 120 normal subjects, TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms were evaluated by PCR-RFLP method recruiting Msp1 and Nco1 restriction enzymes, respectively. IgE serum levels by ELISA technique were determined and asthma diagnosis, treatment and control levels were considered using standard schemes and criteria. Our results indicated that the genotype and allele frequencies of the TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms were not significantly different between control subjects and asthmatics and were not related to in asthma features such as IgE levels, asthma history and pulmonary factors. Wherease some previous studies indicated TLRs and their polymorphisms might have some role in asthma incidence and features, our data demonstrated that TLR2 Arg753Gln and TLR4 Asp299Gly gene variants were not risk factors for asthma or its features in Iranian patients. Genetic complexity, ethnicity, influence of other genes or polymorphisms may overcome these polymorphisms in our asthmatics. PMID:25530138

  15. Pharmacist advice to asthmatics regarding antihistamine use.

    PubMed

    Lantner, R; Tobin, M C

    1991-05-01

    Due to the frequency of asthmatics having concurrent allergic symptoms, patients may seek relief from antihistamines, which are currently labeled with warnings against their use in asthmatics. A survey was conducted in the Chicago area to evaluate the advice rendered by pharmacists regarding the use of antihistamines in asthmatics and their opinions about the current product labeling. Thirty percent of the surveys were returned. Nearly half (48%) of the surveyed pharmacists advise their asthmatic customers to avoid antihistamines and 75% of this group recommend avoidance because they believe antihistamines worsen asthmatic symptoms, despite the lack of sufficient clinical data to support this concern. Only 17% of pharmacists advise that antihistamines pose no problems for asthmatics. The latter group is the most aware that there is controversy surrounding the current labeling. Overall, half the pharmacists surveyed believe the current labeling is not appropriate for patients with asthma. Until the labeling is revised, physicians should be aware that pharmacists may advise their asthmatics against using antihistamines even though antihistamines should be only contraindicated in cases of proven adverse reactions. PMID:2035904

  16. Activity limitation and exertional dyspnea in adult asthmatic patients: What do we know?

    PubMed

    Vermeulen, François; Garcia, Gilles; Ninane, Vincent; Laveneziana, Pierantonio

    2016-08-01

    Limitation of activity is the most cited symptom described by uncontrolled asthma patients. Assessment of activity limitation can be undertaken through several ways, more or less complex, subjective or objective. Yet little is known about the link between patients sensations and objective measurements. The present review reports the current knowledge regarding activity limitation and symptom perception (i.e., exertional dyspnea) in adult patients with asthma. This work is based on references indexed by PubMed, irrespective of the year of publication. Overall, patients with stable asthma do not have a more sedentary lifestyle than healthy subjects. However, during a cycle ergometric test, the maximal load is reduced when FEV1, FVC and muscle strengths are decreased. Additionally, during the six-minute walking test, mild asthma patients walk less than healthy subjects even if the minimal clinically important difference is not reached. The major complaint of asthma patients when exercising is dyspnea that is mainly related to the inspiratory effort and also to dynamic hyperinflation in some circumstances. Finally, the administration of bronchodilator does not improve the ventilatory pattern and the exercise capacity of asthma patients and little is known on its effect on exertional dyspnea. The present review allows to conclude that until now there is no gold standard test allowing the objective assessment of "activity limitation and exertional dyspnea" in asthma patients. PMID:27492522

  17. Spinal anesthesia using Taylor's approach helps avoid general anesthesia in short stature asthmatic patient

    PubMed Central

    Patil, Amarjeet Dnyandeo; Bapat, Manasi; Patil, Sunita A.; Gogna, Roshan Lal

    2015-01-01

    The case history of a 35-year-old female patient with short stature is presented. She was posted for rectopexy in view of rectal prolapse. She was a known case of bronchial asthma. She had crowding of intervertebral spaces, which made administration of spinal anesthesia via the normal route very difficult. Taylor's approach for administration of the same was tried and proved successful, thus saving the patient from receiving general anesthesia in the presence of bronchial asthma, for a perineal surgery. The possible cause for the difficulty in administration of spinal anesthesia and the Taylor's approach are discussed, and reports of similar cases reviewed. PMID:26543472

  18. Quantitative characterization of circadian rhythm of pulmonary function in asthmatic patients treated with inhaled corticosteroids.

    PubMed

    Zhou, Di; Li, Hongshan; Wang, Yaning; Hochhaus, Guenther; Sinha, Vikram; Zhao, Liang

    2015-08-01

    The aim of this study was to characterize the circadian rhythm observed for forced expiratory volume in 1 s (FEV1) in patients with persistent asthma being treated with inhaled corticosteroids. The database included 3379 FEV1 measurements from 189 patients with mild to moderate asthma. A model using the sum of two Sine functions with periods of 12 and 24 h and a constant component of mean circadian rhythm adequately described the circadian rhythm in FEV1 measurements over time. The model adequateness was evaluated by various approaches including visual predictive check (VPC), prediction-corrected VPC, standardized VPC and normalized prediction distribution error. Covariates tested included age, body weight, height, body mass index, baseline FEV1, and sex. Age and height were found to have significant effects on the mean FEV1 level and no covariate was found to have an effect on the magnitude and timing of circadian rhythm. The model predicted that a minimum FEV1 occurred in the early morning and maximum FEV1 occurred in the early afternoon, with a population mean fluctuation of 170 mL, which is consistent with the finding that asthma symptoms usually exacerbate in the early morning for patients with persistent asthma. This developed model provides the first quantitative approach to describing FEV1 circadian rhythm with ICS background treatment and provided insight in designing future registration trials for asthma drug development. PMID:26099861

  19. Respiratory muscle strength in asthmatic children

    PubMed Central

    Marcelino, Alessandra Maria Farias Cavalcante; da Cunha, Daniele Andrade; da Cunha, Renata Andrade; da Silva, Hilton Justino

    2012-01-01

    Summary Introduction: Changes in the respiratory system of asthmatics are also due to the mechanical disadvantage caused by the increased airway resistance. Objective: The study aims to evaluate the respiratory muscle strength and nutritional status of asthmatic children. Method: This is a prospective descriptive and transversal study with 50 children aged 7 to 12 years, who were placed into 2 groups, asthmatic and non-asthmatic. Respiratory muscle strength was evaluated on the basis of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). The nutritional status was evaluated by measuring the anthropometric data, including height, weight, and body mass index (BMI). The findings were subjected to analysis of variance, chi-square, and Student's t test, and p-values < 0.05 was considered statistically significant. Results: In our comparisons, we observed statistically significantly lower values for age, weight, and height in asthmatic patients: 8.52 ± 1.49 years, 30.62 ± 7.66 kg, and 129.85 ± 10.24 cm, respectively, vs. non-asthmatic children(9.79 ± 1.51 years, 39.92 ± 16.57 kg, and 139.04 ± 11.62 cm, respectively). There was no significant increase in MIP and MEP between the groups: MIP was -84.96 ± 27.52 cmH2O for the asthmatic group and -88.56 ± 26.50 cmH2O for the non-asthmatic group, and MEP was 64.48 ± 19.23 cmH2O for asthmatic children and +66.72 ± 16.56 cmH2O for non-asthmatics. Conclusion: There was no statistically significant difference between groups, but we observed that MIP and MEP were slightly higher in the non-asthmatic group than in the asthmatic group. PMID:25991978

  20. Cough and dyspnoea of an asthmatic patient at Mt. Kilimanjaro: a difficult differential diagnosis.

    PubMed

    Goebbels, K; Gieseler, U; Schöffl, Volker; Küpper, Thomas

    2010-01-01

    This case highlights the difficulties associated with the differential diagnosis of pulmonary symptoms in patients with pre-existing diseases in extreme environmental conditions. A 58-year-old man with child-onset allergic asthma developed dyspnoea and an acute non-productive cough during a trekking expedition on Mt. Kilimanjaro (5895m) in Tanzania. The symptoms were believed initially to be linked to the high altitude exposure (high altitude pulmonary oedema (HAPE) or high altitude cough) or his pre-existing asthma. However, he was later diagnosed correctly with a reinfection of Bordetella pertussis. Pertussis is a highly communicable disease with potentially serious medical consequences that could have affected all of the expedition members. The effectiveness of a pertussis vaccine declines 4-12 years after the vaccination. Thus, it is suggested that the status of immunisation against pertussis should be checked along with those of other infections prior to travel. PMID:20188301

  1. Most asthmatics have gastroesophageal reflux with or without bronchodilator therapy.

    PubMed

    Sontag, S J; O'Connell, S; Khandelwal, S; Miller, T; Nemchausky, B; Schnell, T G; Serlovsky, R

    1990-09-01

    The relationship between gastroesophageal reflux and asthma has not been clearly defined. We measured the lower esophageal sphincter pressures and studied gastroesophageal reflux patterns over 24 hours using an ambulatory Gastroreflux Recorder (Del Mar Avionics, Irvine, CA) in 44 controls and 104 consecutive adult asthmatics. The presence or absence of reflux symptoms was not used as a selection criterion for asthmatics. All asthmatics had discrete episodes of diffuse wheezing and documented reversible airway obstruction of at least 20%. Patients underwent reflux testing while receiving, if any, their usual asthmatic medications: 71.2% required chronic bronchodilators and 28.8% required no bronchodilators. Compared with controls, asthmatics had significantly decreased lower esophageal sphincter pressures, greater esophageal acid exposure times, more frequent reflux episodes, and longer clearance times in both the upright and supine positions (P less than 0.0001 for all parameters tested). There were no differences in any of the measured reflux parameters between asthmatics who required bronchodilators and those who did not. Thus, the decreased lower esophageal sphincter pressures and increased levels of acid reflux in asthmatics were not entirely caused by the effects of bronchodilator therapy. Receiver-operating characteristic analysis generated reflux values that discriminated asthmatics from controls. More than 80% of adult asthmatics have abnormal gastroesophageal reflux. We conclude that most adult asthmatics, regardless of the use of bronchodilator therapy, have abnormal gastroesophageal reflux manifested by increased reflux frequency, delayed acid clearance during the day and night, and diminished lower esophageal sphincter pressures. PMID:2379769

  2. Can asthmatic subjects dive?

    PubMed

    Adir, Yochai; Bove, Alfred A

    2016-06-01

    Recreational diving with self-contained underwater breathing apparatus (scuba) has grown in popularity. Asthma is a common disease with a similar prevalence in divers as in the general population. Due to theoretical concern about an increased risk for pulmonary barotrauma and decompression sickness in asthmatic divers, in the past the approach to asthmatic diver candidates was very conservative, with scuba disallowed. However, experience in the field and data in the current literature do not support this dogmatic approach. In this review the theoretical risk factors of diving with asthma, the epidemiological data and the recommended approach to the asthmatic diver candidate will be described. PMID:27246598

  3. Exercise and the asthmatic.

    PubMed

    Bundgaard, A

    1985-01-01

    Physical exercise is not hazardous to asthmatics. Some asthmatics may benefit from physical training, and almost all asthmatics can perform any kind of physical exercise. Free running was earlier thought to induce more asthma than swimming, for example; however, when ventilation is identical during running and swimming, the exercise-induced asthma will also be the same. Hyperventilation alone is as good as physical exercise to induce exercise-induced asthma. If the physical exercise provokes an asthmatic attack, this is most often easily reversed by inhaled beta 2-agonists. Pretreatment of exercise-induced asthma is most efficient by inhaled beta 2-agonist; orally dosed beta 2-agonist is not as efficient as inhaled beta 2-agonist in the pretreatment of exercise-induced asthma. Inhaled sodium cromoglycate diminishes exercise-induced asthma, and the effect seems to be better in children than in adults. Inhaled steroids have no immediate effect on exercise-induced asthma, but long term treatment with steroids diminishes exercise-induced asthma. The pathogenesis of exercise-induced asthma remains obscure. If the water content is low in the inhaled air, e.g. in cold air, the changes in ventilatory capacity following exercise. will be greater than when the exercise is performed while inhaling hot air with high humidity. Almost all asthmatics present changes in the ventilatory capacity following exercise. Seasonal changes in exercise-induced asthma are only present in asthmatics with seasonal allergies, e.g. pollen allergy. No diurnal variation is found in exercise-induced asthma. Asthmatics can do any form of physical exercise. Almost all asthmatics can prevent major changes in ventilatory capacity by pretreatment of exercise-induced asthma or be treated for exercise-induced asthma during the physical activity so that they will not suffer from asthma while performing physical exercise. Asthmatics who have been successfully treated for exercise-induced asthma can do

  4. [The prognosis of asthmatic children with status asthmatics in early childhood].

    PubMed

    Komatsu, Masaki; Ikematsu, Kaori; Tachimoto, Hiroshi; Shukuya, Akinori; Ebisawa, Motohiro

    2002-07-01

    To clarify the prognosis of asthmatic children with status asthmatics in early childhood, we retrospectively investigated 113 patients (boys: 62, girls: 51) who had been treated as status asthmatics since 1995 through 2000 in National Sagamihara Hospital. In this study, the frequency of admission was decreased year by year, 62.8% (1st year), 29.2% (3rd year), and 5% (5th year). All patients were evaluated as severe or moderate patients during the 1st year from the episode of status asthmatics. Three years after the episode, 38% of patients were evaluated as severe or moderate patients. Five years later, only 20% of patients were evaluated as severe or moderate patients and 35% became free from treatment and asthma attack. Most of the patients were treated by DSCG inhalation and RTC therapy. Nine patients needed BDI therapy in addition to DSCG and RTC. With appropriate and careful treatment, the prognosis of the patients who had experienced status asthmatics in the early childhood was kept relatively well. PMID:12201171

  5. Home nebulizer therapy in asthmatics in Qatar.

    PubMed

    Osundwa, V M; Dawod, S T; Ehlayel, M S

    1994-01-01

    We reviewed charts of 50 asthmatic children who were on home nebulizer therapy for treatment of their asthma over a 1-year period. Patients served as their own controls for comparison of the asthma-related variables between periods of 6 months before and 6 months after the initiation of home nebulizer treatment. There was a 74% and 70% reduction in the emergency room visits and hospitalizations, respectively, during the period when the patients were on home nebulizer therapy. We suggest that this form of therapy, if properly used in appropriately selected asthmatic children, will reduce the need for hospital care. PMID:8175625

  6. Peripheral neutrophils after allergic asthmatic reactions.

    PubMed

    Asman, B; Strand, V; Bylin, G; Bergström, K

    1997-01-01

    The response of peripheral neutrophils was studied in 16 patients with allergic asthma after challenge with birch/grass pollen allergen, in order to identify inflammatory markers associated with only the early asthmatic reaction and those associated with both early and late asthmatic reactions. The allergen challenge proceeded until the patients had an early asthmatic reaction with 100% increase in specific airway resistance. Bronchoconstriction after allergen challenge was monitored hourly over 9 h and finally after 18 h, by measurement of the forced expiratory volume in 1 s. Seven patients had a late reaction, defined as a decrease in forced expiratory volume in 1 s of more than 15%. Blood samples were taken before and 18 h after challenge. After allergen challenge (18 h) the blood concentration of neutrophils in patients with a late asthmatic reaction was 1.4 times higher than before challenge and there was a tendency for increased Fc gamma receptor-mediated chemiluminescence. Lewis X-antigen (CD 15), which is associated with endothelial adhesion and extravasation, significantly decreased at the same time. Neutrophils were incubated with the tetrapeptide arginine-glycine-aspartate-serine before and 18 h after allergen challenge. Both patient groups showed an increased Fc gamma receptor-mediated chemiluminescence and a decreased Fc gamma receptor membrane expression following allergen challenge, suggesting a preactivation. In conclusion, patients with a dual asthmatic reaction show a sustained primed inflammatory response and primed neutrophils compared with patients with only an early reaction when measured after the decline of clinical symptoms provoked by allergen challenge. PMID:9352381

  7. Autoradiographic localization of beta-adrenoceptors in asthmatic human lung

    SciTech Connect

    Spina, D.; Rigby, P.J.; Paterson, J.W.; Goldie, R.G. )

    1989-11-01

    The autoradiographic distribution and density of beta-adrenoceptors in human non-diseased and asthmatic bronchi were investigated using (125I)iodocyanopindolol (I-CYP). Analysis of the effects of the beta-adrenoceptor antagonists on I-CYP binding demonstrated that betaxolol (20 nM, beta 1-selective) had no significant effect on specific grain density in either nonasthmatic or asthmatic human bronchus, whereas ICI-118551 (20 nM, beta 2-selective) inhibited I-CYP binding by 85 +/- 9% and 89 +/- 3%, respectively. Thus, homogeneous populations of beta 2-adrenoceptors existed in bronchi from both sources. Large populations of beta-adrenoceptors were localized to the bronchial epithelium, submucosal glands, and airway smooth muscle. Asthmatic bronchial tissue featured epithelial damage with exfoliated cells associated with luminal mucus plugs. A thickened basement membrane and airway smooth muscle hyperplasia were also evident. High levels of specific I-CYP binding were also detected over asthmatic bronchial smooth muscle, as assessed by autoradiography and quantitation of specific grain densities. Isoproterenol and fenoterol were 10- and 13-fold less potent, respectively, in bronchi from asthmatic lung than in those from nonasthmatic lung. However, this attenuated responsiveness to beta-adrenoceptor agonists was not caused by reduced beta-adrenoceptor density in asthmatic airways. A defect may exist in the coupling between beta-adrenoceptors and postreceptor mechanisms in severely asthmatic lung.

  8. Are Asthmatic Children Educationally Handicapped?

    ERIC Educational Resources Information Center

    Bender, Bruce G.

    1995-01-01

    Some asthmatic children demonstrate neurocognitive impairment or interruption in academic progress as a direct or indirect effect of the disease or its treatment. For most asthmatic children these factors do not result in impairment. Those at greatest risk in school adaptation have poorly controlled asthma and are isolated from peers and are…

  9. The use of anti-asthmatic drugs. Do they affect sports performance?

    PubMed

    Fitch, K D

    1986-01-01

    Recent major advances in pharmacological management have provided asthmatics with a satisfactory range of drugs to control asthma. These include sodium cromoglycate (cromolyn sodium), H1-antagonists, belladonna alkaloids, methyl xanthines, glucocorticoids and beta 2-adrenoceptor stimulants. Despite the tendency for most asthmatics to develop bronchoconstriction after exercise, sport and physical activity are now accepted as valuable in the overall management of patients with asthma. Thus, control of exercise-induced asthma (EIA) is essential, if asthmatics are to participate safely in physical activity and without respiratory disadvantage in competitive sport. Fortunately, inhibition or minimization of exercise-induced asthma may be achieved in most asthmatics by pre-exercise aerosol beta 2-agonists supplemented if necessary by sodium cromoglycate and/or theophylline. Regular medication as required to attain and maintain normal ventilatory function throughout each day is the objective in all patients with asthma and appears to be a prerequisiste to control exercise-induced asthma. The introduction of anti-doping controls into high performance sport has presented added difficulties for the asthmatic athlete. Although not always so, currently all of the classes of drugs previously noted are acceptable for the treatment of asthma and exercise-induced asthma. Anomalies may exist in the banning of 2 beta 2-adrenoceptor agonists, fenoterol and orciprenaline (metaproterenol). All sympathomimetic amines with alpha- or predominantly beta-stimulation are banned. The perpetuation of the need to report the use of beta 2-agonists prior to competition appears unnecessary. Although relatively little specific research has been undertaken, there is minimal evidence to suggest that asthmatics can derive any additional ergogenic advantage from medication to control asthma and exercise-induced asthma. beta 2-agonists, sodium cromoglycate and glucocorticoids administered by the aerosol

  10. Platelets from Asthmatic Individuals Show Less Reliance on Glycolysis

    PubMed Central

    Xu, Weiling; Cardenes, Nayra; Corey, Catherine; Erzurum, Serpil C.; Shiva, Sruti

    2015-01-01

    Asthma, a chronic inflammatory airway disease, is typified by high levels of TH2-cytokines and excessive generation of reactive nitrogen and oxygen species, which contribute to bronchial epithelial injury and airway remodeling. While immune function plays a major role in the pathogenesis of the disease, accumulating evidence suggests that altered cellular metabolism is a key determinant in the predisposition and disease progression of asthma. Further, several studies demonstrate altered mitochondrial function in asthmatic airways and suggest that these changes may be systemic. However, it is unknown whether systemic metabolic changes can be detected in circulating cells in asthmatic patients. Platelets are easily accessible blood cells that are known to propagate airway inflammation in asthma. Here we perform a bioenergetic screen of platelets from asthmatic and healthy individuals and demonstrate that asthmatic platelets show a decreased reliance on glycolytic processes and have increased tricarboxylic acid cycle activity. These data demonstrate a systemic alteration in asthma and are consistent with prior reports suggesting that oxidative phosphorylation is more efficient asthmatic individuals. The implications for this potential metabolic shift will be discussed in the context of increased oxidative stress and hypoxic adaptation of asthmatic patients. Further, these data suggest that platelets are potentially a good model for the monitoring of bioenergetic changes in asthma. PMID:26147848

  11. Platelets from Asthmatic Individuals Show Less Reliance on Glycolysis.

    PubMed

    Xu, Weiling; Cardenes, Nayra; Corey, Catherine; Erzurum, Serpil C; Shiva, Sruti

    2015-01-01

    Asthma, a chronic inflammatory airway disease, is typified by high levels of TH2-cytokines and excessive generation of reactive nitrogen and oxygen species, which contribute to bronchial epithelial injury and airway remodeling. While immune function plays a major role in the pathogenesis of the disease, accumulating evidence suggests that altered cellular metabolism is a key determinant in the predisposition and disease progression of asthma. Further, several studies demonstrate altered mitochondrial function in asthmatic airways and suggest that these changes may be systemic. However, it is unknown whether systemic metabolic changes can be detected in circulating cells in asthmatic patients. Platelets are easily accessible blood cells that are known to propagate airway inflammation in asthma. Here we perform a bioenergetic screen of platelets from asthmatic and healthy individuals and demonstrate that asthmatic platelets show a decreased reliance on glycolytic processes and have increased tricarboxylic acid cycle activity. These data demonstrate a systemic alteration in asthma and are consistent with prior reports suggesting that oxidative phosphorylation is more efficient asthmatic individuals. The implications for this potential metabolic shift will be discussed in the context of increased oxidative stress and hypoxic adaptation of asthmatic patients. Further, these data suggest that platelets are potentially a good model for the monitoring of bioenergetic changes in asthma. PMID:26147848

  12. Nerve growth factor levels and localisation in human asthmatic bronchi.

    PubMed

    Olgart Höglund, C; de Blay, F; Oster, J P; Duvernelle, C; Kassel, O; Pauli, G; Frossard, N

    2002-11-01

    Nerve growth factor (NGF) has recently been suggested to be an important mediator of inflammation. In support of this, serum levels of NGF have been shown to be enhanced in asthmatics. However, it has not yet been shown whether the levels of NGF are also altered locally in asthmatic airways, when compared with healthy subjects, and the localisation of potential sources of NGF in the human bronchus have not yet been described. The aim of the present study was to assess NGF levels in bronchoalveolar lavage fluid (BALF) from asthmatics and to compare them to those of control subjects. Furthermore, the authors wanted to localise potential sources of NGF in bronchial tissue, and to number NGF-immunopositive infiltrating cells in the bronchial submucosa. BALF and bronchial biopsies were obtained from seven control subjects and seven asthmatic patients by fibreoptic bronchoscopy. NGF protein levels were quantified by enzyme-linked immunosorbent assay in BALF. NGF localisation was examined by immunohistochemistry on bronchial biopsy sections. The asthmatics exhibited significantly enhanced NGF levels in BALF. Intense NGF-immunoreactivity was observed in bronchial epithelium, smooth muscle cells and infiltrating inflammatory cells in the submucosa, and to a lesser extent in the connective tissue. The asthmatics exhibited a higher number of NGF-immunoreactive infiltrating cells in the bronchial submucosa than control subjects. This study provides evidence that nerve growth factor is locally produced in the airways, and shows that this production is enhanced in asthmatics. These findings suggest that nerve growth factor is produced by both structural cells and infiltrating inflammatory cells in human bronchus in vivo, and the authors suggest that the increase in nerve growth factor protein in bronchoalveolar lavage fluid observed in asthmatic patients may originate both from structural cells, producing increased nerve growth factor levels in inflammatory conditons, and from

  13. Depressive symptoms amongst asthmatic children's caregivers.

    PubMed

    Szabó, Alexandra; Mezei, Györgyi; Kovári, Eva; Cserháti, Endre

    2010-06-01

    We wanted to find out, whether the number of depressive symptoms is higher amongst asthmatic children's caregivers, compared to international data, to the Hungarian population average, and to parents of children with chronic renal disease. Are these depressive symptoms connected to the children's psychological status, asthma severity or current asthma symptoms? One-hundred and eight, 7- to 17-yr-old asthmatic children were enrolled, who have been treated at the Semmelweis University, First Department of Pediatrics. Children were suffering from asthma for at least 1 yr, with a median of 8 yr (1-16 yr), they started to develop asthmatic symptoms between the age of 0.5-14 yr (median: 3 yr). We also identified 27 children with chronic renal diseases and their caregivers, who functioned as a control group. Children were asked to complete the Hungarian-validated versions of the Child Depression Inventory, the Spielberger State Anxiety Inventory for Children and the Juniper Pediatric Asthma Quality of Life Questionnaire. Asthma severity and current symptoms were also documented, 56% had no symptoms on the preceding week. Caregivers were asked to complete the Hungarian versions of the Beck Depression Inventory (BDI) short form, the Spielberger Anxiety Inventory and the Juniper Pediatric Asthma Caregivers' Quality of Life Questionnaire. Caregivers of asthmatic children had significantly more depressive symptoms (7.73 +/- 6.69 s.d.) than the age-specific normal population (p < 0.01). Caregivers of renal patients also experience more depressive symptoms (9.61 +/- 7.43 s.d.) than their healthy peers, but difference between the two chronic diseases' group did not prove to be significant. Asthmatic children's caregivers who scored more points on the BDI than the population average suffer from more anxiety symptoms, but their quality of life is not worse than the caregivers' with less depressive points. Depressive symptoms were neither connected to the children's psychological

  14. Clostridium butyricum in combination with specific immunotherapy converts antigen-specific B cells to regulatory B cells in asthmatic patients

    PubMed Central

    Liao, Hong-Ying; Tao, Li; Zhao, Jian; Qin, Jie; Zeng, Gu-Cheng; Cai, Song-Wang; Li, Yun; Zhang, Jian; Chen, Hui-Guo

    2016-01-01

    The effect of antigen specific immunotherapy (SIT) on asthma is supposed to be improved. Published data indicate that administration of probiotics alleviates allergic diseases. B cells play important roles in the pathogenesis of allergic diseases. This study aims to modulate antigen specific B cell property by the administration of Clostridium butyrate (CB) in combination with SIT. The results showed that after a 3-month treatment, the total asthma clinical score and serum specific IgE were improved in the patients treated with SIT, which was further improved in those treated with both SIT and CB, but not in those treated with CB alone. Treatment with SIT and CB increased p300 and STAT3 activation, up regulated the IL-10 gene transcription and increased the frequency of peripheral antigen specific B cells. In conclusion, administration with SIT in combination with CB converts Der p 1 specific B cells to regulatory B cells in asthma patients allergic to Der p 1. The data suggest a potential therapeutic remedy in the treatment of allergic diseases. PMID:26857726

  15. An investigation of aeroallergens affecting urban Malaysian asthmatics.

    PubMed

    Sam, C K; Soon, S C; Liam, C K; Padmaja, K; Cheng, H M

    1998-03-01

    We investigated the aeroallergens affecting 200 asthmatics from the University Hospital in Kuala Lumpur, Malaysia and found 164 (82%) patients with skin prick test (SPT) reactivity to one or more of a panel of 14 allergens, which included indoor and outdoor animal and plant aeroallergens. Reactivity was most frequent to the indoor airborne allergens, with 159 (79.5%) reacting to either or both house dust mite (Dermatophagoides) species and 87 (43.5%) to cockroach. The SPT reactivity to house dust mites corresponded with the finding that patients found house dust to be the main precipitant of asthmatic attacks. PMID:9681124

  16. Subjective psychological symptoms in outpatient asthmatic adolescents.

    PubMed

    Lebowitz, M D; Thompson, H C; Strunk, R C

    1981-12-01

    Outpatient adolescent asthmatics were studied using the Asthma Symptom Checklist (ASC) of Kinsman et al. The study showed that outpatient asthmatic adolescents are similar in many respects to older institutionalized asthmatics, except that in the former, psychological symptoms are more diffuse and recognition of respiratory symptoms is less severe. Further studies are needed to determine which psychological symptoms are most important in predicting prognosis in affected asthmatics or the development of "psychosomatic" asthma. PMID:7338897

  17. Differential deposition of fibronectin by asthmatic bronchial epithelial cells.

    PubMed

    Ge, Qi; Zeng, Qingxiang; Tjin, Gavin; Lau, Edmund; Black, Judith L; Oliver, Brian G G; Burgess, Janette K

    2015-11-15

    Altered ECM protein deposition is a feature in asthmatic airways. Fibronectin (Fn), an ECM protein produced by human bronchial epithelial cells (HBECs), is increased in asthmatic airways. This study investigated the regulation of Fn production in asthmatic or nonasthmatic HBECs and whether Fn modulated HBEC proliferation and inflammatory mediator secretion. The signaling pathways underlying transforming growth factor (TGF)-β1-regulated Fn production were examined using specific inhibitors for ERK, JNK, p38 MAPK, phosphatidylinositol 3 kinase, and activin-like kinase 5 (ALK5). Asthmatic HBECs deposited higher levels of Fn in the ECM than nonasthmatic cells under basal conditions, whereas cells from the two groups had similar levels of Fn mRNA and soluble Fn. TGF-β1 increased mRNA levels and ECM and soluble forms of Fn but decreased cell proliferation in both cells. The rate of increase in Fn mRNA was higher in nonasthmatic cells. However, the excessive amounts of ECM Fn deposited by asthmatic cells after TGF-β1 stimulation persisted compared with nonasthmatic cells. Inhibition of ALK5 completely prevented TGF-β1-induced Fn deposition. Importantly, ECM Fn increased HBEC proliferation and IL-6 release, decreased PGE2 secretion, but had no effect on VEGF release. Soluble Fn had no effect on cell proliferation and inflammatory mediator release. Asthmatic HBECs are intrinsically primed to produce more ECM Fn, which when deposited into the ECM, is capable of driving remodeling and inflammation. The increased airway Fn may be one of the key driving factors in the persistence of asthma and represents a novel, therapeutic target. PMID:26342086

  18. PCSK9 inhibition in patients with hypercholesterolemia.

    PubMed

    Desai, Nihar R; Sabatine, Marc S

    2015-10-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that plays an important role in modulating low-density lipoprotein cholesterol (LDL-C) levels by targeting LDL-C receptors for lysosomal degradation. Genetic association studies have demonstrated that loss-of-function mutations in PCSK9 are associated with low plasma LDL-C levels and a reduction in the incidence of adverse cardiovascular events. Monoclonal antibodies directed against PCSK9 have been developed and have been shown in phase 1, 2, and 3 trials to dramatically reduce LDL-C regardless of background lipid-lowering therapy, including in clinically challenging populations such as patients intolerant to statin therapy and those with familial hypercholesterolemia. To date, the clinical trials have not raised any significant safety concerns, with no appreciable excess of myalgias, elevation in aminotransferases, or other adverse events. Large, cardiovascular outcomes trials are underway to assess definitively the efficacy and safety of 3 monoclonal antibodies (evolocumab, alirocumab, and bococizumab), while additional non-monoclonal antibody approaches to inhibit PCSK9 continue in the early-phase development. PMID:25771732

  19. TAMPA ASTHMATIC CHILDREN'S STUDY (TACS)

    EPA Science Inventory

    The Tampa Asthmatic Children's Study (TACS) was a pilot research study to assess methodologies and research instruments needed for including asthma as a health outcome in the National Children's Study (NCS). This was one of a series of pilot studies focusing on (a) simple, cos...

  20. Bronchoconstrictive effect of ultrasonic nebulized distilled water on asthmatic children.

    PubMed

    Baba, Y; Hayashida, M; Yasunami, J; Takamatsu, I; Adachi, K; Toyoshima, K

    1989-01-01

    We studied the airway responsiveness of asthmatic and normal children to ultrasonic nebulized distilled water (UNDW inhalation test). It was found that this stimulus induced a fall in FEV1 (forced expiratory volume in 1 s) in asthmatic children, but little fall in normal children. This airway response was shown to be reproducible at about 2-week intervals. The more severe the asthma, the higher the percentage of the responders to the UNDW inhalation test, and the greater the fall in FEV1. The results of the UNDW inhalation test did not correlate with that of acetylcholine inhalation test or of exercise-induced asthma (EIA). UNDW-induced bronchoconstriction was inhibited by premedication with disodium cromoglycate (DSCG) (20 mg) or inhaled ipratropium bromide (40 micrograms). Jet-nebulized distilled water induced little fall in FEV1 in asthmatic children. These data suggest that UNDW-induced bronchoconstriction may involve the release of chemical mediators from the mast cells and cholinergic pathways. We conclude that UNDW inhalation test is a safe, less burdensome, and rather convenient method to evaluate clinically nonspecific airway hyperresponsiveness in asthmatic children. PMID:2534983

  1. Plasminogen activator inhibitor-1 in sputum and nasal fluids increases in asthmatics during common colds

    PubMed Central

    Cho, Seong H.; Hong, Seung J.; Chen, Haimei; Habib, Ali; Cho, David; Lee, Sun H.; Kang, Joseph; Ward, Theresa; Boushey, Homer A.; Schleimer, Robert P.; Avila, Pedro C.

    2014-01-01

    Capsule Summary This study showed that sputum and nasal lavage levels of plasminogen activator inhibitor-1 (PAI-1) rise during a common cold in asthmatic patients. This rise may contribute to the progression of airway remodeling. PMID:24373352

  2. Manifold significance of serum eosinophil cationic protein in asthmatic children.

    PubMed

    Zubović, Ivan; Rozmanić, Vojko; Ahel, Vladimir; Banac, Srdan

    2002-01-01

    Asthma is the result of complex interaction between different cells, mediators and nervous system that leads to an inflammatory response accompanied by increased bronchial hyperactivity. Its clinical manifestations include recurrent cough, wheezing and difficult breathing. The purpose of this study was to establish the possibility of diagnosing inflammation in asthmatic patients based on the assessment of serum eosinophil cationic protein (ECP), and of following the efficacy of asthmatic treatment by the levels of inflammation mediators. In a prospective study, 134 children aged 1 to 18 (mean 8) years underwent serum ECP assessment. Experimental group included 87 patients with asthma, 56 boys and 31 girls, mean age 9.1 (range 2-17) years. Control group included patients with recurrent non-allergic disorders, 27 boys and 20 girls aged 1-16 (mean 6.1) years. Serum ECP was assessed using the Pharmacia CAP system ECP-FEIA method, i.e. fluoroimmunoassay test for quantitative assessment of serum ECP levels. Serum values of ECP were significantly higher in asthmatics than in controls (p = 0.001). Our results showed that increased levels of serum ECP to significantly correlate with increased eosinophil (p = 0.018) and immunoglobulin E (p = 0.003) levels. Increased ECP levels reflect the degree of inflammation and correlate with the clinical picture severity in asthmatic patients. Assessment of serum ECP levels can reveal eosinophilic activity, and indirectly detect immunologic inflammation in asthmatics. It is possible to follow the dynamics of immunologic inflammation during the course of treatment as well as treatment efficacy. PMID:12596625

  3. BET Bromodomains Regulate Transforming Growth Factor-β-induced Proliferation and Cytokine Release in Asthmatic Airway Smooth Muscle*

    PubMed Central

    Perry, Mark M.; Durham, Andrew L.; Austin, Philip J.; Adcock, Ian M.; Chung, Kian Fan

    2015-01-01

    Airway smooth muscle (ASM) mass is increased in asthma, and ASM cells from patients with asthma are hyperproliferative and release more IL-6 and CXCL8. The BET (bromo- and extra-terminal) family of proteins (Brd2, Brd3, and Brd4) govern the assembly of histone acetylation-dependent chromatin complexes. We have examined whether they modulate proliferation and cytokine expression in asthmatic ASM cells by studying the effect of BET bromodomain mimics JQ1/SGCBD01 and I-BET762. ASM cells from healthy individuals and nonsevere and severe asthmatics were pretreated with JQ1/SGCBD01 and I-BET762 prior to stimulation with FCS and TGF-β. Proliferation was measured by BrdU incorporation. IL-6 and CXCL8 release was measured by ELISA, and mRNA expression was measured by quantitative RT-PCR. ChIP using a specific anti-Brd4 antibody and PCR primers directed against the transcriptional start site of IL-6 and CXCL8 gene promoters was performed. Neither JQ1/SGCBD01 nor I-BET762 had any effect on ASM cell viability. JQ1/SGCBD01 and I-BET762 inhibited FCS+TGF-β-induced ASM cell proliferation and IL-6 and CXCL8 release in healthy individuals (≥ 30 nm) and in nonsevere and severe asthma patients (≥100 nm), with the latter requiring higher concentrations of these mimics. JQ1/SGCBD01 reduced Brd4 binding to IL8 and IL6 promoters induced by FCS+TGF-β. Mimics of BET bromodomains inhibit aberrant ASM cell proliferation and inflammation with lesser efficiency in those from asthmatic patients. They may be effective in reducing airway remodeling in asthma. PMID:25697361

  4. Nutritional status and physical inactivity in moderated asthmatics

    PubMed Central

    Bruno, Andreina; Uasuf, Carina Gabriela; Insalaco, Giuseppe; Barazzoni, Rocco; Ballacchino, Antonella; Gjomarkaj, Mark; Pace, Elisabetta

    2016-01-01

    Abstract Preservation of nutritional status and of fat-free mass (FFM) and/or preventing of fat mass (FM) accumulation have a positive impact on well-being and prognosis in asthma patients. Physical inactivity is identified by World Health Organization as the fourth leading risk factor for global mortality. Physical activity (PA) may contribute to limit FM accumulation, but little information is available on the interactions between habitual PA and body composition and their association with disease severity in asthma severity. Associations between habitual PA, FM, FFM, and pulmonary function were investigated in 42 subjects (24 patients with mild-moderate asthma and 18 matched control subjects). Sensewear Armband was used to measure PA and metabolic equivalent of tasks (METs) continuously over 4 days, while body composition was measured by bioelectrical impedance analysis. Respiratory functions were also assessed in all study participants. FM and FFM were comparable in mild-moderate asthmatics and controls, but PA was lower in asthmatics and it was negatively correlated with FM and positively with the FFM marker body cell mass in all study subjects (P < 0.05). Among asthmatics, treated moderate asthmatics (ICS, n = 12) had higher FM and lower PA, METs, steps number/die, and forced expiratory volume in the 1st second (FEV1)/forced vital capacity (FVC) than in untreated intermittent asthmatics (UA, n = 12). This pilot study assesses that in mild-moderate asthma patients, lower PA is associated with higher FM and higher disease severity. The current results support enhancement of habitual PA as a potential tool to limit FM accumulation and potentially contribute to preserve pulmonary function in moderate asthma, considering the physical inactivity a strong risk factor for asthma worsening. PMID:27495092

  5. In vitro histamine release from basophils of asthmatic and atopic individuals in D/sub 2/O

    SciTech Connect

    Tung, R.; Lichtenstein, L.M.

    1982-05-01

    It was found that spontaneous histamine release from human basophils in H/sub 2/O-based buffers is negligible; in D/sub 2/O-based buffers, however, release is observed with the cells of some donors. Analysis of this phenomenon revealed release from the basophils of 1 of 22 control individuals (5%), 15 of 47 patients with allergic rhinitis (32%), and 14 of 20 asthmatic patients (70%). The difference between both patient groups and controls and between atopics and asthmatics was highly significant. That D/sub 2/O release was not cytotoxic is suggested by the finding that 37/sup 0/ was optimal, with inhibition at 4/sup 0/C or 46/sup 0/C as well as by EDTA, 2-deoxyglucose, and dibromoacetophenone, an inhibitor of phospholipase A/sub 2/. The release mechanism was unusual in that dibutyryl cAMP and agonists that cause an increase in cAMP lead to no inhibition. No correlation was noted between the total serum IgE level (and thus the number of IgE receptors on the basophil surface) and the magnitude of D/sub 2/O release. No increase in D/sub 2/O release was observed in 17 ragweed-sensitive patients through a ragweed season. A unique property of D/sub 2/O release was the loss of reactivity by preincubating cells at 37/sup 0/C for 30 min before adding D/sub 2/O. Non-D/sub 2/O-reactive cells could be ''converted'' to D/sub 2/O-reactive cells by incubation with antigen in the whole blood phase during leukocyte isolation; these cells showed the same loss of releaseability at 37/sup 0/C and an inhibitor profile similar to D/sub 2/O-responsive cells from ragweed allergic or asthmatic patients. We suggest that D/sub 2/O-based buffers reveal, in atopic and asthmatic patients, in vivo basophil activation; whether this is due to IgE cross-links, to C split products, or to other stimuli is not yet clear.

  6. A study of airway smooth muscle in asthmatic and non-asthmatic airways using PS-OCT (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Adams, David C.; Holz, Jasmin A.; Szabari, Margit V.; Hariri, Lida P.; Harris, R. Scott; Cho, Jocelyn L.; Hamilos, Daniel L.; Luster, Andrew D.; Medoff, Benjamin D.; Suter, Melissa J.

    2016-03-01

    Present understanding of the pathophysiological mechanisms of asthma has been severely limited by the lack of an imaging modality capable of assessing airway conditions of asthma patients in vivo. Of particular interest is the role that airway smooth muscle (ASM) plays in the development of asthma and asthma related symptoms. With standard Optical Coherence Tomography (OCT), imaging ASM is often not possible due to poor structural contrast between the muscle and surrounding tissues. A potential solution to this problem is to utilize additional optical contrast factors intrinsic to the tissue, such as birefringence. Due to its highly ordered structure, ASM is strongly birefringent. Previously, we demonstrated that Polarization Sensitive OCT(PS-OCT) has the potential to be used to visualize ASM as well as easily segment it from the surrounding (weakly) birefringent tissue by exploiting a property which allows it to discriminate the orientation of birefringent fibers. We have already validated our technology with a substantial set of histological comparisons made against data obtained ex vivo. In this work we present a comprehensive comparison of ASM distributions in asthmatic and non-asthmatic human volunteers. By isolating the ASM we parameterize its distribution in terms of both thickness and band width, calculated volumetrically over centimeters of airway. Using this data we perform analyses of the asthmatic and non-asthmatic airways using a broad number and variety and subjects.

  7. Antisaccade performance in Korsakoff patients reveals deficits in oculomotor inhibition.

    PubMed

    Van der Stigchel, Stefan; Reichenbach, Roderick C L; Wester, Arie J; Nijboer, Tanja C W

    2012-01-01

    Oculomotor inhibition reflects the ability to suppress an unwanted eye movement. The goal of the present study was to assess oculomotor inhibition in patients with Korsakoff's syndrome (KS). To this end, an antisaccade task was employed in which an eye movement towards an onset stimulus has to be inhibited, and a voluntary saccade has to be executed in the opposite direction. Compared to the results of a matched control group, patients showed a higher percentage of intrusive saccades, made more antisaccade errors, and showed longer latencies on prosaccade trials. These results clearly show that oculomotor inhibition is impaired in KS. Part of these deficits in oculomotor inhibition may be explained by neuronal atrophy in the frontal areas, which is generally associated with KS. PMID:22712532

  8. Preoperative administration of etoricoxib in patients undergoing hip replacement causes inhibition of inflammatory mediators and pain relief

    PubMed Central

    Renner, B; Walter, G; Strauss, J; Fromm, MF; Zacher, J; Brune, K

    2012-01-01

    Objective Administering cyclooxygenase-2 inhibitors preoperatively appears attractive since these drugs reduce post-operative pain, but do not increase the risk of post-operative bleeds, asthmatic attacks and stress-related gastrointestinal ulcers. In a former investigation, we could show that post-operative administration of etoricoxib reduces prostaglandin production in wound fluid, but the onset of action is variable due to delayed post-operative absorption. Methods In this study, we investigated the preoperative administration of etoricoxib in patients undergoing hip replacement. They received 120 mg etoricoxib or placebo 2 h before surgery and 1 day after in a double-blinded, randomized, parallel group design. Results A total of 11 patients were randomized (placebo n = 5; verum n = 6). We found high and constant levels of the drug in blood, central nervous system and wound fluid already at the end of surgery (tmax < 2 h). This was accompanied by inhibition of prostaglandin production in the wound tissue (treatment p < 0.05), suppression of interleukin 6 increase in plasma (treatment p < 0.01), and – despite existing standard pain relief procedures – higher satisfaction with analgesics (time vs. treatment p < 0.05) and less demand for opioids (treatment p < 0.01) and intrathecal bupivacaine (treatment p = 0.05) administration. Conclusion Administration of etoricoxib 2 h before surgery allows for an effective drug concentration in critical tissues, a reduction of the production of pro-inflammatory mediators and for better pain relief. PMID:22337568

  9. Cessation of dexamethasone exacerbates airway responses to methacholine in asthmatic mice.

    PubMed

    Stengel, Peter W; Nickell, Laura E; Wolos, Jeffrey A; Snyder, David W

    2007-06-01

    In asthmatic mice, dexamethasone (30.0 mg/kg) was administered orally once daily on Days 24-27. One hour after dexamethasone on Day 25-27, the mice were exposed to ovalbumin aerosols. Twenty-eight days after the initial ovalbumin immunization, we found that dexamethasone reduced methacholine-induced pulmonary gas trapping and inhibited bronchoalveolar lavage eosinophils and neutrophils. However, five days after the last dose of dexamethasone and last ovalbumin aerosol exposure in other asthmatic mice, the airway obstructive response to methacholine was exacerbated in dexamethasone-treated mice compared to vehicle-treated mice on Day 32. Further, eosinophils, but not neutrophils, were still inhibited after cessation of dexamethasone. Thus, discontinuing dexamethasone worsened methacholine-induced pulmonary gas trapping of asthmatic mice in the absence of eosinophilic airway inflammation. PMID:17374534

  10. Body Mass Index and Comorbidities in Adult Severe Asthmatics

    PubMed Central

    Bruno, Andreina; Pace, Elisabetta; Cibella, Fabio; Chanez, Pascal

    2014-01-01

    Both severe asthma and obesity are growing health problems. Severe asthma leads to a poor quality of life. The relationship among BMI, comorbidities, and severe asthma control in adults is still unclear. The aim of the study is to better understand the effect of the comorbidities as atopy, type II diabetes, OSAS, gastroesophageal reflux, hypertension, cardiovascular diseases, osteoporosis, infections, and psychological factors with BMI on asthma control in a cohort of adult severe asthmatics. One hundred and two patients were enrolled in a cross-sectional study assessing asthma control, treatments, pulmonary function, inflammatory markers, and comorbidities. Patients were divided into 3 classes according to BMI: normal weight, overweight, and obese. We found that the optimal state of asthma control is lower. whereas the score of Asthma Control Questionnaire, the number of asthma exacerbations during last year, the oral corticosteroids requirement during the previous year, and the LABA treatments are higher in obese than in overweight and normal weight severe asthmatics. The number of subjects with type II diabetes and OSAS are higher among obese and overweight patients than in normal weight asthmatics. In conclusion, BMI represents per se a factor for the deterioration in disease control in severe asthma. PMID:24987694

  11. p53 Codon 72 Genetic Polymorphism in Asthmatic Children: Evidence of Interaction With Acid Phosphatase Locus 1.

    PubMed

    Saccucci, Patrizia; Verrotti, Alberto; Giannini, Cosimo; Verini, Marcello; Chiarelli, Francesco; Neri, Anna; Magrini, Andrea

    2014-05-01

    Several lines of evidence are implicating an increased persistence of apoptotic cells in patients with asthma. This is largely due to a combination of inhibition, or defects in the apoptotic process and/or impaired apoptotic cell removal mechanisms. Among apoptosis-inducing genes, an important role is played by p53. In the present study, we have investigated the possible relationship between p53 codon 72 polymorphism and asthma and the interaction with ACP1, a genetic polymorphism involved in the susceptibility to allergic asthma. We studied 125 asthmatic children and 123 healthy subjects from the Caucasian population of Central Italy. p53 codon 72 and ACP1 polymorphisms were evaluated using a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method. There is a statistically significant association between p53 codon 72 polymorphism and allergic asthma: Arg/Arg genotype is more represented in asthmatic patients than in controls (P=0.018). This association, however, is present in subjects with low ACP1 activity A/A and A/B only (P=0.023). The proportion of children with A/A and A/B genotype carrying Arg/Arg genotype is significantly high in asthmatic children than in controls (OR=1.941; 95% C.I. 1.042-3.628). Our finding could have important clinical implications since the subjects with A/A and A/B genotypes of ACP1 carrying Arg/Arg genotype are more susceptible to allergic asthma than Pro/Pro genotype. PMID:24843801

  12. The level of submicron fungal fragments in homes with asthmatic children

    PubMed Central

    Seo, SungChul; Choung, Ji Tae; Chen, Bean T.; Lindsley, William G.; Kim, Ki Youn

    2015-01-01

    Objectives Much scientific evidence indicates a positive association between moldy environments and respiratory illnesses and/or symptoms (e.g., asthma). Recently, submicron fungal fragments (< 1.0 µm) have been suggested as a potential contributor to adverse health effects due to their biological composition (e.g., antigens, mycotoxins, and (1,3)-β-d-glucan) as well as their small size. However, the contribution of exposure to fine fungal particles on adverse health outcomes has been poorly characterized, particularly in homes with asthmatic children. We characterized the airborne level of smaller-sized fungal particles between homes with and without asthmatic children. Methods We visited 29 homes with (n = 15) and without (n = 14) an asthmatic child and sampled submicron fungal fragments in a living room and child's bedroom, along with outdoor sampling, using the NIOSH two-stage sampler. (1,3)-β-d-glucan of fungal fragments analyzed by Limulus Amebocyte lysate assay (LAL) was used for quantifying their exposure. Results Overall, the geometric mean (GM) concentration of (1,3)-β-d-glucan in submicron fungal fragments in indoor air was two-fold higher in homes with asthmatic children (50.9 pg/m3) compared to homes with non-asthmatic children (26.7 pg/m3) (P < 0.001). The GM concentration of these particles in child's bedroom in homes with an asthmatic child (66.1 pg/m3) was about three times higher than that in homes with non-asthmatic children (23.0 pg/m3) (P < 0.001). The relative humidity had a negative correlation with the concentration of (1,3)-β-d-glucan in submicron fungal fragments (Pearson coefficient = −0.257, P = 0.046). Conclusions Our findings indicate that homes with asthmatic children have a higher concentration of submicron fungal fragments compared to homes with non-asthmatic children. A greater exposure to smaller-sized fungal particles may occur in homes with an asthmatic child as relative humidity decreases. The very careful control of

  13. Effects of isoproterenol on IL-2 and cAMP production in peripheral T cells from asthmatic and non-asthmatic subjects sensitive to Candida.

    PubMed

    Aihara, M; Dobashi, K; Horie, T; Iizuka, K; Nakazawa, T; Mori, M

    1999-09-01

    Immunity to Candida albicans (Candida) is characterized by a Th-1 type pattern of reactivity. Candida is rarely a cause antigen for bronchial asthma. Beta agonists have been found to inhibit secretion of IL-2 from T cells through intracellular cAMP elevation. We examined effects of isoproterenol (ISO) on Candida-stimulated T cells. Peripheral T cells obtained from six Candida-sensitive asthmatics, six Candida-sensitive non-asthmatic subjects, and six normal donors by Ficoll-Hypaque gradient centrifugation and nylon-wool column chromatography were incubated with Candida antigen or concanavalin A (Con A) in the absence or presence of ISO. Secretion of IL-2 and intracellular accumulation of cAMP were assayed by ELISA. Con A induced secretion of IL-2 in each of the three groups. Candida antigen induced IL-2 secretion in the normal and the non-asthmatic subjects, but not in the asthmatics. ISO, which reduced Con A-induced secretion of IL-2 in a dose-dependent manner, had no effect on Candida-induced secretion of IL-2. Although ISO increased the intracellular concentration of cAMP in untreated and Con A-treated T cells from all donors, cells from the normal and the non-asthmatic subjects, but not from the asthmatics, that were co-incubated with ISO and Candida had lower levels of cAMP than those treated with ISO alone. It is suggested that Candida antigen induces secretion of IL-2 and reduces ISO-inducible accumulation of cAMP in Candida-responsive IL-2 secreting cells, which may make Candida-induced secretion of IL-2 insensitive to ISO. PMID:10572628

  14. Arterial Stiffness, Distensibility, and Strain in Asthmatic Children

    PubMed Central

    Özkan, Esra Akyüz; Serin, Halil İbrahim; Khosroshahi, Hashem E.; Kılıç, Mahmut; Ekim, Meral; Beysel, Perihan; Geçit, U. Aliye; Domur, Esra

    2016-01-01

    Background We hypothesized that since asthma is a chronic inflammatory disease, it could lead to the early development of atherosclerosis in childhood-onset asthma. The aim of this study was to investigate arterial stiffness, distensibility, and strain of different peripheral arteries, the parameters of which can be used to detect atherosclerosis in asthmatic children. Material/Methods We studied 22 pediatric patients with asthma and 18 healthy children. Fasting blood glucose and cholesterol levels were evaluated to exclude children with diabetes and hyperlipidemia, which are risk factors for atherosclerosis. Renal, carotid, and brachial arteries diameters were measured. Using the measured data, stiffness, distensibility, and strain of the arteries of all children were calculated. Results Pulse pressure, systolic and diastolic blood pressure, heart rate, cholesterols, and glucose levels of the obese individuals were similar to the controls. In carotid arteries there were no statistical differences regarding stiffness, distensibility, and strain. According to multiple ANCOVA analysis, distensibility and strain of right and left brachial arteries and right renal artery were higher, whereas right renal artery stiffness was lower in asthmatic children than in controls. Approximately one-fifth of the change in the left and right brachial arteries and right renal artery distensibility and strain and a small portion of the change in the right renal artery stiffness were associated with asthma. In contrast, left renal artery distensibility, strain, and stiffness were not associated with asthma. Conclusions Peripheral arteries had higher distensibility and strain, and lower stiffness in asthmatic children than in controls. PMID:26803723

  15. Nocturnal symptoms and sleep disturbances in clinically stable asthmatic children.

    PubMed

    Chugh, Inder Mohan; Khanna, Puneet; Shah, Ashok

    2006-01-01

    Presence of nocturnal symptoms is related to asthma severity. Clinically stable asthmatic children, too, report frequent nocturnal symptoms and sleep disturbances. The study determined these parameters in stable, asthmatic children, in their home environment. This case-control, questionnaire-based study in 70 school-going children comprised 40 asthmatics (Group 1) and 30, age/gender matched, healthy children (Group 2). Parents maintained peak expiratory flow (PEF) and sleep diaries for one week. Group 1 had significantly lower mean morning (250.3 vs. 289.1 I/minute) and mean evening PEF values (261.7 vs. 291.3 I/minute). Group 1 (38.95%), reported frequent nocturnal symptoms like cough (36.90%), breathlessness (32.80%), wheeze (27.68%) and chest tightness (14.35%). Sleep disturbances, significant in Group 1 (38, 95% vs. 14.35%), included daytime sleepiness (24.60%), daytime tiredness (20.50%), difficulty in maintaining sleep (15.38%), early morning awakening (14.35%), struggle against sleep during daytime (12.30%), and involuntarily falling asleep (17.43%). On a scale of 1-6, Group 1 scored significant sleep disturbances/patient (3 vs. 0.8); lethargy/tiredness in morning (2.9 vs. 2.2), poorer sleep quality (4.7 vs. 5.4), less parents' satisfaction with child's sleep (4.5 vs. 5.5) and daytime fitness (4.1 vs. 5.3). Group 1, when exposed to environmental tobacco smoke (22, 55%), reported significant nocturnal symptoms (18/22, 81%) and reduced mean morning and evening PEF values (17/22, 77%). It is concluded that clinically stable, asthmatic children reported increased nocturnal symptoms, sleep disturbances and poorer sleep quality. Lack of awareness of asthma-sleep association and its clinical implications could lead to poor asthma control and impaired daytime activity. PMID:17136879

  16. Non-Anticoagulant Fractions of Enoxaparin Suppress Inflammatory Cytokine Release from Peripheral Blood Mononuclear Cells of Allergic Asthmatic Individuals

    PubMed Central

    Horne, James; Zaidi, Syed Tabish R.; Sohal, Sukhwinder Singh; Peterson, Gregory M.; Korner, Heinrich; Patel, Rahul P.

    2015-01-01

    Background Enoxaparin, a low-molecular-weight heparin, is known to possess anti-inflammatory properties. However, its clinical exploitation as an anti-inflammatory agent is hampered by its anticoagulant effect and the associated risk of bleeding. Objective The aim of the current study was to examine the ability of non-anticoagulant fractions of enoxaparin to inhibit the release of key inflammatory cytokines in primed peripheral blood mononuclear cells derived from allergic mild asthmatics. Methods Peripheral blood mononuclear cells from allergic asthmatics were activated with phytohaemag glutinin (PHA), concanavalin-A (ConA) or phorbol 12-myristate 13-acetate (PMA) in the presence or absence of enoxaparin fractions before cytokine levels were quantified using specific cytokine bead arrays. Together with nuclear magnetic resonance analysis,time-dependent and target-specific effects of enoxaparin fractions were used to elucidate structural determinants for their anti-inflammatory effect and gain mechanistic insights into their anti-inflammatory activity. Results Two non-anticoagulant fractions of enoxaparin were identified that significantly inhibited T-cell activation. A disaccharide fraction of enoxaparin inhibited the release of IL-4, IL-5, IL-13 and TNF-α by more than 57% while a tetrasaccharide fraction was found to inhibit the release of tested cytokines by more than 68%. Our data suggest that the observed response is likely to be due to an interaction of 6-O-sulfated tetrasaccharide with cellular receptor(s). Conclusion and Clinical Relevance The two identified anti-inflammatory fractions lacked anticoagulant activity and are therefore not associated with risk of bleeding. The findings highlight the potential therapeutic use of enoxaparin-derived fractions, in particular tetrasaccharide, in patients with chronic inflammatory disorders. PMID:26046354

  17. Fewer Inhaled Steroids May Be OK for Asthmatic Children

    MedlinePlus

    ... gov/medlineplus/news/fullstory_159083.html Fewer Inhaled Steroids May Be OK for Asthmatic Children Study suggests ... 2016 FRIDAY, May 27, 2016 (HealthDay News) -- Inhaled steroid therapy is commonly used to treat asthmatic children ...

  18. Educating Asthmatic Children in European Ambulatory Pediatrics: Facts and Insights.

    PubMed

    Robberecht, Marie Noëlle; Beghin, Laurent; Deschildre, Antoine; Hue, Valérie; Reali, Laura; Plevnik-Vodušek, Vesna; Moretto, Marilena; Agustsson, Sigurlaug; Tockert, Emile; Jäger-Roman, Elke; Deplanque, Dominique; Najaf-Zadeh, Abolfazl; Martinot, Alain

    2015-01-01

    The aim of this study was to assess the role of European ambulatory pediatricians in caring for asthmatic children, especially in terms of their therapeutic education. We developed a survey that was observational, declarative, retrospective and anonymous in nature. 436 ambulatory pediatricians in Belgium, France, Germany, Italy, Luxembourg and Slovenia were asked to participate in the survey providing information on three children over 6 years old suffering from persistent asthma, who had been followed for at least 6 months. We considered the pediatricians' profile, and their role in the therapeutic education of children. 277 pediatricians (64%) responded: 81% were primary care pediatricians; 46% participated in networks; 4% had specific training in Therapeutic Patient Education; 69% followed more than 5 asthmatic children per month, and over long periods (7 ± 4 years). The profiles of 684 children were assessed. Answers diverged concerning the provision of a Personalized Action Plan (60-88%), training the child to measure and interpret his Peak Expiratory Flow (31-99%), and the prescription of pulmonary function tests during the follow-up programme of consultations (62-97%). Answers converged on pediatricians' perception of their role in teaching children about their condition and its treatment (99%), about inhalation techniques (96%), and in improving the children's ability to take preventive measures when faced with risk situations (97%). This study highlights the role of European pediatricians in caring for asthmatic children, and their lack of training in Therapeutic Patient Education. Programmes and tools are required in order to train ambulatory pediatricians in Therapeutic Patient Education, and such resources should be integrated into primary health care, and harmonized at the European level. PMID:26061153

  19. Educating Asthmatic Children in European Ambulatory Pediatrics: Facts and Insights

    PubMed Central

    Robberecht, Marie Noëlle; Beghin, Laurent; Deschildre, Antoine; Hue, Valérie; Reali, Laura; Plevnik-Vodušek, Vesna; Moretto, Marilena; Agustsson, Sigurlaug; Tockert, Emile; Jäger-Roman, Elke; Deplanque, Dominique; Najaf-Zadeh, Abolfazl; Martinot, Alain

    2015-01-01

    The aim of this study was to assess the role of European ambulatory pediatricians in caring for asthmatic children, especially in terms of their therapeutic education. We developed a survey that was observational, declarative, retrospective and anonymous in nature. 436 ambulatory pediatricians in Belgium, France, Germany, Italy, Luxembourg and Slovenia were asked to participate in the survey providing information on three children over 6 years old suffering from persistent asthma, who had been followed for at least 6 months. We considered the pediatricians’ profile, and their role in the therapeutic education of children. 277 pediatricians (64%) responded: 81% were primary care pediatricians; 46% participated in networks; 4% had specific training in Therapeutic Patient Education; 69% followed more than 5 asthmatic children per month, and over long periods (7 ± 4 years). The profiles of 684 children were assessed. Answers diverged concerning the provision of a Personalized Action Plan (60–88%), training the child to measure and interpret his Peak Expiratory Flow (31–99%), and the prescription of pulmonary function tests during the follow-up programme of consultations (62–97%). Answers converged on pediatricians’ perception of their role in teaching children about their condition and its treatment (99%), about inhalation techniques (96%), and in improving the children’s ability to take preventive measures when faced with risk situations (97%). This study highlights the role of European pediatricians in caring for asthmatic children, and their lack of training in Therapeutic Patient Education. Programmes and tools are required in order to train ambulatory pediatricians in Therapeutic Patient Education, and such resources should be integrated into primary health care, and harmonized at the European level. PMID:26061153

  20. Asthmatic responses to airborne acid aerosols.

    PubMed Central

    Ostro, B D; Lipsett, M J; Wiener, M B; Selner, J C

    1991-01-01

    BACKGROUND: Controlled exposure studies suggest that asthmatics may be more sensitive to the respiratory effects of acidic aerosols than individuals without asthma. This study investigates whether acidic aerosols and other air pollutants are associated with respiratory symptoms in free-living asthmatics. METHODS: Daily concentrations of hydrogen ion (H+), nitric acid, fine particulates, sulfates and nitrates were obtained during an intensive air monitoring effort in Denver, Colorado, in the winter of 1987-88. A panel of 207 asthmatics recorded respiratory symptoms, frequency of medication use, and related information in daily diaries. We used a multiple regression time-series model to analyze which air pollutants, if any, were associated with health outcomes reported by study participants. RESULTS: Airborne H+ was found to be significantly associated with several indicators of asthma status, including moderate or severe cough and shortness of breath. Cough was also associated with fine particulates, and shortness of breath with sulfates. Incorporating the participants' time spent outside and exercise intensity into the daily measure of exposure strengthened the association between these pollutants and asthmatic symptoms. Nitric acid and nitrates were not significantly associated with any respiratory symptom analyzed. CONCLUSIONS: In this population of asthmatics, several outdoor air pollutants, particularly airborne acidity, were associated with daily respiratory symptoms. PMID:1851397

  1. Asthmatic responses to airborne acid aerosols

    SciTech Connect

    Ostro, B.D.; Lipsett, M.J.; Wiener, M.B.; Selner, J.C. )

    1991-06-01

    Controlled exposure studies suggest that asthmatics may be more sensitive to the respiratory effects of acidic aerosols than individuals without asthma. This study investigates whether acidic aerosols and other air pollutants are associated with respiratory symptoms in free-living asthmatics. Daily concentrations of hydrogen ion (H+), nitric acid, fine particulates, sulfates and nitrates were obtained during an intensive air monitoring effort in Denver, Colorado, in the winter of 1987-88. A panel of 207 asthmatics recorded respiratory symptoms, frequency of medication use, and related information in daily diaries. We used a multiple regression time-series model to analyze which air pollutants, if any, were associated with health outcomes reported by study participants. Airborne H+ was found to be significantly associated with several indicators of asthma status, including moderate or severe cough and shortness of breath. Cough was also associated with fine particulates, and shortness of breath with sulfates. Incorporating the participants' time spent outside and exercise intensity into the daily measure of exposure strengthened the association between these pollutants and asthmatic symptoms. Nitric acid and nitrates were not significantly associated with any respiratory symptom analyzed. In this population of asthmatics, several outdoor air pollutants, particularly airborne acidity, were associated with daily respiratory symptoms.

  2. Effects of salbutamol and enantiomers on allergen-induced asthmatic reactions and airway hyperreactivity.

    PubMed

    Westerhof, F J; Zuidhof, A B; Kok, L; Meurs, H; Zaagsma, J

    2005-05-01

    Salbutamol consists of a racemic mixture of R- and S-salbutamol. R-salbutamol (levalbuterol) is the active bronchodilating enantiomer, whereas S-salbutamol is thought to be pharmacologically inactive or to exert adverse effects. This study evaluated the bronchoprotective effects of inhalation of therapeutically relevant doses of the racemate and individual enantiomers in guinea pigs. It was found that basal airway reactivity to histamine was similarly reduced 30 min after inhalation of equivalent doses of RS- and R-salbutamol; this protective effect disappeared within 3 h. Inhalation of RS- and R-salbutamol 30 min before and 5.5 h after allergen challenge suppressed allergen-induced airway hyperreactivity to histamine after the early and late asthmatic reaction, completely inhibiting the early asthmatic reaction and tending to reduce the development of the late asthmatic reaction. At 5 h after allergen challenge, the inhibition of airway hyperreactivity was more pronounced in animals treated with R-salbutamol compared to racemate-treated animals. Both basal airway reactivity and allergen-induced hyperreactivity were not affected by S-salbutamol. Inflammatory cell infiltration was not affected by the racemate or the individual enantiomers. In conclusion, inhalation of therapeutically relevant doses of R- and RS-salbutamol effectively suppress allergen-induced airway reactivity after the early and late asthmatic reactions, the R-enantiomer being slightly more potent with respect to early airway reactivity than the racemate. No adverse effects were observed for the S-enantiomer. PMID:15863644

  3. [Exercise-induced airway obstruction in asthmatic children and adolescents].

    PubMed

    Zapletal, A; Zbojan, J; Pohanka, V

    1992-03-01

    In 115 asymptomatic asthmatic children and adolescents (age 6-18 years) there was studied the magnitude of airway obstruction, induced by various physical efforts and assessed from the recording of maximum expiratory flow-volume curves and in some patients by "specific" airway conductance measurement in a body plethysmograph. The effects of 5 minutes free running outdoors, 5 minutes of exercise on a bicycle ergometer (2 watts/kg of body weight), routine swimming training in swimming pool and of forced expiration maneuver on the magnitude of airway obstruction were assessed. The most frequent and largest degree of airway obstruction was observed after 5 min. free running outdoors (heart rate after running 160-200/min). The obstruction was revealed in 80-100% asthmatics in various groups. The chosen lung function parameters showed exercise-induced airway obstruction in the same patients in various proportions as well as the magnitude of the obstruction. Following free running outdoors the values of maximum expiratory flow at 25% of vital capacity and "specific" airway conductance were most reduced. Spontaneous retreat of obstruction was observed in the course of 2 hours. The physical exercise on a bicycle ergometer was a small stimulus in inducing of airway obstruction. The swimming in a pool did not provoke any obstruction. In 10% of our asthmatics airway obstruction was observed following forced expiration maneuver. Airway obstruction induced by 5 minutes free running outdoors and assessed best by flow-volume curves appeared as a suitable test in the assessment of airway hyperresponsiveness. PMID:1591810

  4. Esculetin Attenuates Th2 and Th17 Responses in an Ovalbumin-Induced Asthmatic Mouse Model.

    PubMed

    Hongyan, Long

    2016-04-01

    The purpose of the current study was to investigate the anti-asthmatic effect of esculetin (ES) and explore its potential mechanism with a mouse model of allergic asthma. A total number of 50 mice were randomly assigned to five groups: control, model, dexamethasone (Dex, 2 mg/kg), and ES (20 mg/kg, 40 mg/kg). Mouse asthma model was developed with the sensitization and challenge of ovalbumin (OVA). The levels of IgE in serum, eosinophilia infiltration, Th2/Th17 cytokines, Th17 cell frequency, histological condition, and the protein expressions of RORγt, GATA3 were detected. Our study demonstrated that ES inhibited, OVA-induced eosinophil count, interleukin-4 (IL-4), IL-5, IL-13, and IL-17A levels were recovered in bronchoalveolar lavage fluid. Flow cytometry (FCM) studies revealed that ES substantially inhibited Th17 cells' percentage. Western blot study also indicated that ES downregulated RORγt and GATA3 expressions. Meanwhile, ES had beneficial effects on the histological alteration. These findings suggested that ES might effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma. PMID:26797918

  5. Sustained release theophylline for the forgetful asthmatic.

    PubMed

    Weinstein, A G

    1985-10-01

    Several theophylline pharmacologic strategies were tested for the forgetful medication-dependent asthmatic who frequently initiates treatment from below the therapeutic range of 10 to 20 micrograms/mL. Theodur was found to give comparable if not higher levels (two, eight, and 24 hours) starting from 0 microgram/mL than Slophyllin Gyrocap during a multiple dose 28-hour study. In a single dose 12-hour study, Theodur 100-mg tablets gave higher levels during the first nine hours than Theodur 200-mg tablets. Theodur 100-mg tablets may be preferred for the forgetful asthmatic who can sustain pulmonary function despite greater fluctuation with theophylline levels. PMID:4051262

  6. Identification and quantification of phosphodiesterase 4 subtypes in CD4 and CD8 lymphocytes from healthy and asthmatic subjects

    PubMed Central

    Landells, L J; Szilagy, C M; Jones, N A; Banner, K H; Allen, J M; Doherty, A; O'Connor, B J; Spina, D; Page, C P

    2001-01-01

    In the present study, for the first time, PDE4 subtypes were identified and semi-quantified in both CD4 and CD8 lymphocytes from healthy and asthmatic individuals. CD4 and CD8 lymphocytes from healthy and mild asymptomatic asthmatic subjects (receiving β-agonist therapy only) were isolated from peripheral venous blood using appropriate antibody coated paramagnetic beads. PDE4 subtypes and β-actin were identified by digoxigenin (DIG)-labelling reverse transcriptase-polymerase chain reaction and semi-quantified by DIG-detection enzyme-linked immunosorbance assay. In CD4 and CD8 lymphocytes PDE4A, PDE4B and PDE4D were detected, with no significant differences observed between healthy and asthmatic groups. In CD8 lymphocytes, enzyme subtype expression was lower and showed more intersubject variability. In functional studies investigating the effects of various PDE inhibitors on PHA-induced proliferation of mononuclear cells from healthy and asthmatic subjects, CDP840 (0.03–10 μM), rolipram (0.1–10 μM) and theophylline (10 μM–1 mM) inhibited PHA-induced proliferation of mononuclear cells from healthy and asthmatic subjects in a concentration-dependent manner, although no significant difference was observed between the groups investigated. In additional studies, total monocyte cyclic AMP PDE activity was investigated in cells isolated from asthmatic subjects both prior to and 24 h after allergen challenge. Total monocyte cyclic AMP PDE activity remained unaffected following challenge of asthmatic subjects with either house dust mite or cat dander and was inhibited in a concentration-dependent manner by rolipram (0.01–100 μM) both before and after allergen challenge. PMID:11429397

  7. Modification of the late asthmatic reaction by hyposensitization in asthmatic children allergic to house dust mite (Dermatophagoides pteronyssinus) or grass pollen.

    PubMed

    Van Bever, H P; Bosmans, J; De Clerck, L S; Stevens, W J

    1988-07-01

    The frequency and severity of the late asthmatic reaction (LAR) was studied in asthmatic children allergic to house dust mite (HDM) or grass pollen (GP) with and without hyposensitization (HS). The four groups were comparable according to their severity of asthma. All children were allergic to HDM (Dermatophagoides pteronyssinus) or GP according to history, skin testing and specific IgE determination via the RAST. The LAR occurred less frequently (29% versus 73%) (P less than 0.001) and was less severe in children receiving HS. The difference was significant between the children allergic to HDM as well as between children allergic to GP. The immediate asthmatic reaction (IAR) was also less severe in children allergic to HDM who received HS, compared to those who never received HS, (P = 0.033) although the PD20 of the HDM challenge (PD20HDM) was not different between the two groups. In children allergic to GP, there was no difference in PD20 of the GP challenge (PD20GP) or in severity of the IAR, whether the children received HS or not. There was no difference between the PD20HDM in patients who developed a LAR and in patients who did not. There was no relation between the type of asthmatic reaction following the allergen provocation test and the level of circulating immune complexes (CIC) and the level of house dust mite-specific IgG (IgGHDM) or grass pollen-specific IgE (IgGGP) in the different groups, determined before the challenge. There was a decrease in the level of IgG containing CIC (IgGCIC) during the LAR. It is concluded that the LAR occurs less frequently and is less severe in asthmatic children who receive HS. PMID:3414914

  8. Hypoxia Exerts Dualistic Effects on Inflammatory and Proliferative Responses of Healthy and Asthmatic Primary Human Bronchial Smooth Muscle Cells

    PubMed Central

    Keglowich, Laura; Baraket, Melissa; Tamm, Michael; Borger, Peter

    2014-01-01

    Background For oxygen supply, airway wall cells depend on diffusion though the basement membrane, as well as on delivery by micro-vessels. In the asthmatic lung, local hypoxic conditions may occur due to increased thickness and altered composition of the basement membrane, as well as due to edema of the inflamed airway wall. Objective In our study we investigated the effect of hypoxia on proliferation and pro-inflammatory and pro-angiogenic parameter production by human bronchial smooth muscle cells (BSMC). Furthermore, conditioned media of hypoxia-exposed BSMC was tested for its ability to induce sprout outgrowth from endothelial cells spheroids. Methods BSMC were cultured in RPMI1640 (5% FCS) under normoxic (21% O2) and hypoxic (1% and 5% O2) conditions. Proliferation was determined by cell count and Western blot analysis for cyclin E and Proliferating Cell Nuclear Antigen (PCNA). Secretion of IL-6, IL-8, ENA-78 and VEGF-A was analyzed by ELISA. BSMC conditioned medium was tested for its angiogenic capacity by endothelial cell (EC)-spheroid in vitro angiogenesis assay. Results Proliferation of BSMC obtained from asthmatic and non-asthmatic patients was significantly reduced in the presence of 1% O2, whereas 5% O2 reduced proliferation of asthmatic BSMC only. Hypoxia induced HIF-1α expression in asthmatic and non-asthmatic BSMC, which coincided with significantly increased release of IL-6, IL-8 and VEGF-A, but not ENA-78. Finally, endothelial sprout outgrowth from EC spheroids was increased when exposed to hypoxia conditioned BSMC medium. Conclusion Hypoxia had dualistic effects on proliferative and inflammatory responses of asthmatic and non-asthmatic BSMC. First, hypoxia reduced BSMC proliferation. Second, hypoxia induced a pro-inflammatory, pro-angiogenic response. BSMC and EC may thus be promising new targets to counteract and/or alleviate airway wall remodeling. PMID:24587090

  9. Activated p38 MAPK in Peripheral Blood Monocytes of Steroid Resistant Asthmatics

    PubMed Central

    Li, Ling-bo; Leung, Donald Y. M.; Goleva, Elena

    2015-01-01

    Steroid resistance is a significant problem in management of chronic inflammatory diseases, including asthma. Accessible biomarkers are needed to identify steroid resistant patients to optimize their treatment. This study examined corticosteroid resistance in severe asthma. 24 asthmatics with forced expiratory volume in one second of less then 80% predicted were classified as steroid resistant or steroid sensitive based on changes in their lung function following a week of treatment with oral prednisone. Heparinised blood was collected from patients prior to oral prednisone administration. Phosphorylated mitogen activated kinases (MAPK) (extracellular regulated kinase (ERK), p38 and jun kinase (JNK)) were analyzed in whole blood samples using flow cytometry. Activation of phospho-p38 MAPK and phospho-mitogen- and stress-activated protein kinase 1 (MSK1) in asthmatics’ peripheral blood mononuclear cells (PBMC) were confirmed by Western blot. Dexamethasone suppression of the LPS-induced IL-8 mRNA production by steroid resistant asthmatics PBMC in the presence of p38 and ERK inhibitors was evaluated by real time PCR. Flow cytometry analysis identified significantly stronger p38 phosphorylation in CD14+ monocytes from steroid resistant than steroid sensitive asthmatics (p = 0.014), whereas no difference was found in phosphorylation of ERK or JNK in CD14+ cells from these two groups of asthmatics. No difference in phosphorylated p38, ERK, JNK was detected in CD4+, CD8+ T cells, B cells and NK cells from steroid resistant vs. steroid sensitive asthmatics. P38 MAPK pathway activation was confirmed by Western blot, as significantly higher phospho-p38 and phospho-MSK1 levels were detected in the PBMC lysates from steroid resistant asthmatics. P38 inhibitor significantly enhanced DEX suppression of LPS-induced IL-8 mRNA by PBMC of steroid resistant asthmatics. This is the first report demonstrating selective p38 MAPK pathway activation in blood monocytes of steroid

  10. THE TAMPA ASTHMATIC CHILDREN'S STUDY (TACS)

    EPA Science Inventory

    Conduct field monitoring studies with asthmatic children to identify and quantify factors that effect personal exposures in real-world environments and use the results of these studies to develop simple questions and/or measurements for classifying exposure in large studies as ...

  11. ASSESSING EXPOSURE FACTORS OF ASTHMATIC CHILDREN

    EPA Science Inventory

    Since 1980, there has been a 75% increase in the prevalence of asthma in children in the U.S.

    A pilot study was conducted in a southeastern US city to develop and to evaluate methods and factors associated with asthmatic children's (< 6 yrs.) exposures to air pollutants. ...

  12. Effect of Compliance for Chronic Asthmatic Children.

    ERIC Educational Resources Information Center

    Cluss, Patricia A.; And Others

    1984-01-01

    Examined whether chronically asthmatic children (N=11) found to be noncompliant to their daily theophylline regimen, differed from their more compliant peers (N=11). Results indicated that wheezing and variability in lung function were significantly less well-controlled in the noncompliant group. (LLL)

  13. Vitamin E prevents NRF2-suppression by allergen in asthmatic alveolar macrophages in vivo

    PubMed Central

    Dworski, Ryszard; Han, Wei; Blackwell, Timothy S.; Hoskins, Aimee; Freeman, Michael L.

    2011-01-01

    Asthma is a chronic inflammatory airway disease associated with increased generation of reactive oxidant species and disturbed antioxidant defenses. NRF2 is the master transcription factor that regulates the expression of Phase II antioxidant and detoxifying enzymes. Disruption of NRF2 augments oxidative stress and inflammation in a mouse model of asthma suggesting a protective role of NRF2 in the lungs in vivo. Yet, little is known about the regulation and function of NRF2 in human asthmatics. Using segmental allergen challenge, a well established experimental model of IgE-mediated asthma exacerbation in human atopic asthmatics, we investigated the effect of a specific allergen and the modulatory role of vitamin E on NRF2 and a NRF2-target gene, superoxide dismutase, in alveolar macrophages recovered from the airways at 24h after allergen instillation in vivo. Allergen-provoked airway inflammation in sensitive asthmatics caused a profound inhibition of macrophage NRF2 activity and superoxide dismutase, rendering them incapable of responding to the NRF2 inducers. Prolonged treatment with high doses of the antioxidant vitamin E lessened this allergen-induced drop in alveolar macrophage NRF2. These results are the first to demonstrate that NRF2 expression in human asthmatics is compromised upon allergen challenge but can be rescued by vitamin E in vivo. PMID:21605660

  14. Characterization of a “high” TNF-α phenotype in moderate-to-severe asthmatic children

    PubMed Central

    Brown, Sheena D.; Brown, Lou Ann; Stephenson, Susan; Dodds, Jennifer C.; Douglas, Shaneka L.; Qu, Hongyan; Fitzpatrick, Anne M.

    2015-01-01

    Summary Systemic TNF-α expression is increased in a subset of children with moderate-to-severe asthma despite aggressive corticosteroid treatment and is associated with poor asthma control. Phenotypic-directed TNF-α inhibition may be of benefit in some asthmatic children. PMID:25725987

  15. Effects of hypercapnia and hypocapnia on respiratory resistance in normal and asthmatic subjects.

    PubMed

    van den Elshout, F J; van Herwaarden, C L; Folgering, H T

    1991-01-01

    The effects of hypercapnia and hypocapnia on respiratory resistance were studied in 15 healthy subjects and 30 asthmatic subjects. Respiratory resistance (impedance) was measured with the pseudo-random noise forced oscillation technique while the subjects rebreathed from a wet spirometer in a closed respiratory circuit in which end tidal carbon dioxide tension (PCO2) could be controlled. Hypercapnia was induced by partially short circuiting the carbon dioxide absorber, and hypocapnia by voluntary hyperventilation. The circulating air was saturated with water vapour and kept at body temperature and ambient pressure. A rise of end tidal PCO2 of 1 kPa caused a significant fall in respiratory resistance in both normal and asthmatic subjects (15% and 9% respectively). A fall of PCO2 of 1 kPa did not cause any significant change in impedance in the control group. In the asthmatic patients resistance increased by 13%, reactance fell by 45%, and the frequency dependence of resistance rose 240%. These findings confirm that hypocapnia may contribute to airway obstruction in asthmatic patients, even when water and heat loss are prevented. PMID:1908137

  16. Nutritional status and physical inactivity in moderated asthmatics: A pilot study.

    PubMed

    Bruno, Andreina; Uasuf, Carina Gabriela; Insalaco, Giuseppe; Barazzoni, Rocco; Ballacchino, Antonella; Gjomarkaj, Mark; Pace, Elisabetta

    2016-08-01

    Preservation of nutritional status and of fat-free mass (FFM) and/or preventing of fat mass (FM) accumulation have a positive impact on well-being and prognosis in asthma patients. Physical inactivity is identified by World Health Organization as the fourth leading risk factor for global mortality. Physical activity (PA) may contribute to limit FM accumulation, but little information is available on the interactions between habitual PA and body composition and their association with disease severity in asthma severity.Associations between habitual PA, FM, FFM, and pulmonary function were investigated in 42 subjects (24 patients with mild-moderate asthma and 18 matched control subjects). Sensewear Armband was used to measure PA and metabolic equivalent of tasks (METs) continuously over 4 days, while body composition was measured by bioelectrical impedance analysis. Respiratory functions were also assessed in all study participants.FM and FFM were comparable in mild-moderate asthmatics and controls, but PA was lower in asthmatics and it was negatively correlated with FM and positively with the FFM marker body cell mass in all study subjects (P < 0.05). Among asthmatics, treated moderate asthmatics (ICS, n = 12) had higher FM and lower PA, METs, steps number/die, and forced expiratory volume in the 1st second (FEV1)/forced vital capacity (FVC) than in untreated intermittent asthmatics (UA, n = 12).This pilot study assesses that in mild-moderate asthma patients, lower PA is associated with higher FM and higher disease severity. The current results support enhancement of habitual PA as a potential tool to limit FM accumulation and potentially contribute to preserve pulmonary function in moderate asthma, considering the physical inactivity a strong risk factor for asthma worsening. PMID:27495092

  17. Increased nuclear suppressor of cytokine signaling 1 in asthmatic bronchial epithelium suppresses rhinovirus induction of innate interferons

    PubMed Central

    Gielen, Vera; Sykes, Annemarie; Zhu, Jie; Chan, Brian; Macintyre, Jonathan; Regamey, Nicolas; Kieninger, Elisabeth; Gupta, Atul; Shoemark, Amelia; Bossley, Cara; Davies, Jane; Saglani, Sejal; Walker, Patrick; Nicholson, Sandra E.; Dalpke, Alexander H.; Kon, Onn-Min; Bush, Andrew; Johnston, Sebastian L.; Edwards, Michael R.

    2015-01-01

    Background Rhinovirus infections are the dominant cause of asthma exacerbations, and deficient virus induction of IFN-α/β/λ in asthmatic patients is important in asthma exacerbation pathogenesis. Mechanisms causing this interferon deficiency in asthmatic patients are unknown. Objective We sought to investigate the expression of suppressor of cytokine signaling (SOCS) 1 in tissues from asthmatic patients and its possible role in impaired virus-induced interferon induction in these patients. Methods We assessed SOCS1 mRNA and protein levels in vitro, bronchial biopsy specimens, and mice. The role of SOCS1 was inferred by proof-of-concept studies using overexpression with reporter genes and SOCS1-deficient mice. A nuclear role of SOCS1 was shown by using bronchial biopsy staining, overexpression of mutant SOCS1 constructs, and confocal microscopy. SOCS1 levels were also correlated with asthma-related clinical outcomes. Results We report induction of SOCS1 in bronchial epithelial cells (BECs) by asthma exacerbation–related cytokines and by rhinovirus infection in vitro. We found that SOCS1 was increased in vivo in bronchial epithelium and related to asthma severity. SOCS1 expression was also increased in primary BECs from asthmatic patients ex vivo and was related to interferon deficiency and increased viral replication. In primary human epithelium, mouse lung macrophages, and SOCS1-deficient mice, SOCS1 suppressed rhinovirus induction of interferons. Suppression of virus-induced interferon levels was dependent on SOCS1 nuclear translocation but independent of proteasomal degradation of transcription factors. Nuclear SOCS1 levels were also increased in BECs from asthmatic patients. Conclusion We describe a novel mechanism explaining interferon deficiency in asthmatic patients through a novel nuclear function of SOCS1 and identify SOCS1 as an important therapeutic target for asthma exacerbations. PMID:25630941

  18. Prevalence of DSM IV anxiety and affective disorders in a pediatric population of asthmatic children and adolescents.

    PubMed

    Vila, G; Nollet-Clemençon, C; de Blic, J; Mouren-Simeoni, M C; Scheinmann, P

    2000-06-01

    A series of 82 children and adolescents with moderate and severe persistent asthma was studied. Their psychopathological problems were compared to those of 82 healthy subjects, matched for age, sex and socio-economic status. The patients completed the Child Depression Inventory, an inventory of fears and anxiety (ECAP) and the Coopersmith Self Esteem Inventory. Parents of asthmatic children filled in the Child Behavior Check List to assess their social competence. The patients were examined with the revised Kiddie Schedule for Affective Disorders and Schizophrenia. There were more anxiety symptoms in the asthmatic group than in the control group. Asthmatics were not significantly more depressed than controls and their self-esteem was as good. We found 29 anxiety disorders, four affective disorders and four disruptive behavior disorders. Generalized anxiety disorder was the main diagnosis (n=24). The asthmatic subgroup presenting anxiety and affective disorders had poorer self esteem, fewer activities and worse social competence than other asthmatics and controls. Adolescents did not seem to have more emotional disturbances than younger patients. Girls did not have more DSM IV anxiety or affective disorders than boys. PMID:10802131

  19. Novel therapeutic strategies for adult obese asthmatics

    PubMed Central

    Linderholm, Angela; Bratt, Jennifer; Schuster, Gertrud; Zeki, Amir; Kenyon, Nicholas J.

    2014-01-01

    Synopsis Asthma is a complex syndrome that affects an estimated 26 million people in the United States but gaps exist in the recognition and management of asthmatic subgroups. In this manuscript, we propose alternative approaches for future treatments of adult obese asthmatics that do not respond to standard controller therapies of inhaled corticosteroids, bronchodilators, and anti-leukotriene drugs. We draw parallels between seemingly disparate therapeutics through their common signaling pathways. Specifically, we describe how metformin and statins can potentially improve airway inflammation and suggest supplements, for example L-arginine, which can be used in combination with conventional therapies. A move towards more targeted therapies for asthma subgroups is needed. These therapies address asthma and the comorbidities that accompany obesity and metabolic syndrome to provide the greatest therapeutic potential. PMID:25282293

  20. A novel inhaled Syk inhibitor blocks mast cell degranulation and early asthmatic response.

    PubMed

    Ramis, Isabel; Otal, Raquel; Carreño, Cristina; Domènech, Anna; Eichhorn, Peter; Orellana, Adelina; Maldonado, Mónica; De Alba, Jorge; Prats, Neus; Fernández, Joan-Carles; Vidal, Bernat; Miralpeix, Montserrat

    2015-09-01

    Spleen tyrosine kinase (Syk) is essential for signal transduction of immunoreceptors. Inhibition of Syk abrogates mast cell degranulation and B cell responses. We hypothesized that Syk inhibition in the lung by inhaled route could block airway mast cells degranulation and the early asthmatic response without the need of systemic exposure. We discovered LAS189386, a novel Syk inhibitor with suitable properties for inhaled administration. The aim of this study was to characterize the in vitro and in vivo profile of LAS189386. The compound was profiled in Syk enzymatic assay, against a panel of selected kinases and in Syk-dependent cellular assays in mast cells and B cells. Pharmacokinetics and in vivo efficacy was assessed by intratracheal route. Airway resistance and mast cell degranulation after OVA challenge was evaluated in an ovalbumin-sensitized Brown Norway rat model. LAS189386 potently inhibits Syk enzymatic activity (IC50 7.2 nM), Syk phosphorylation (IC50 41 nM), LAD2 cells degranulation (IC50 56 nM), and B cell activation (IC50 22 nM). LAS189386 inhibits early asthmatic response and airway mast cell degranulation without affecting systemic mast cells. The present results support the hypothesis that topical inhibition of Syk in the lung, without systemic exposure, is sufficient to inhibit EAR in rats. Syk inhibition by inhaled route constitutes a promising therapeutic option for asthma. PMID:26051661

  1. Treatment of bronchial obstruction in asthmatic children.

    PubMed

    Spicak, V; Kacirek, S; Pohunek, P

    1987-01-01

    In asthmatic children, clenbuterol causes bronchodilatation for 12h. Ipratropium bromide plus fenoterol is effective in stopping dry irritable cough related to bronchial obstruction. Sustained-release theophylline is effective with therapeutic serum and saliva concentrations for 16h. Ambroxol hydrochloride provides an additional therapy for bronchial obstructure since it reduces cough and sputum output. Cromoglycate and ketotifen are appropriate for long term treatment, and a combination of bronchodilators may offer better control of nocturnal asthma. PMID:3664019

  2. Assessment of anxiety disorders in asthmatic children.

    PubMed

    Vila, G; Nollet-Clémençon, C; de Blic, J; Falissard, B; Mouren-Simeoni, M C; Scheinmann, P

    1999-01-01

    The study's objective was to determine whether the State Trait Anxiety Inventory for Children, Trait version (STAIC), is suitable for the assessment of DSM-IV anxiety disorders in asthmatic children and adolescents. Ninety-two outpatients were given a semistructured diagnostic interview. They completed STAIC; another questionnaire about anxiety, the Echelle Comportementale d'Anxiété et de Peurs (ECAP); and the Child Depression Inventory. The parents filled in the Child Behavior Check-List (CBCL) and the Conners Parent Rating Scale (CPRS). A group of healthy children was assessed with STAIC. Thirty asthmatic children had anxiety disorders. They had significantly higher STAIC scores than the nonanxious asthmatic and the nonasthmatic children. STAIC scores were independent of age and sex and were correlated with ECAP, CPRS anxiety subscore, CBCL total score, internalizing score, and CBCL anxiety-depression subscore. Internal consistency was 0.75. With a threshold value of 34 for anxiety disorders, this method had a sensitivity of 73% and a specificity of 70%. STAIC was thus a useful method for anxiety disorder screening in a pediatric population. PMID:10479945

  3. Allergic and asthmatic reactions to alcoholic drinks.

    PubMed

    Vally, Hassan; Thompson, Philip J

    2003-03-01

    Alcoholic drinks are capable of triggering a wide range of allergic and allergic-like responses, including rhinitis, itching, facial swelling, headache, cough and asthma. Limited epidemiological data suggests that many individuals are affected and that sensitivities occur to a variety of drinks, including wine, beer and spirits. In surveys of asthmatics, over 40% reported the triggering of allergic or allergic-like symptoms following alcoholic drink consumption and 30 - 35% reported worsening of their asthma. Sensitivity to ethanol itself can play a role in triggering adverse responses, particularly in Asians, which is due mainly to a reduced capacity to metabolize acetaldehyde. In Caucasians, specific non-alcohol components are the main cause of sensitivities to alcoholic drinks. Allergic sensitivities to specific components of beer, spirits and distilled liquors have been described. Wine is clearly the most commonly reported trigger for adverse responses. Sensitivities to wine appear to be due mainly to pharmacological intolerances to specific components, such as biogenic amines and the sulphite additives. Histamine in wine has been associated with the triggering of a wide spectrum of adverse symptoms, including sneezing, rhinitis, itching, flushing, headache and asthma. The sulphite additives in wine have been associated with triggering asthmatic responses. Clinical studies have confirmed sensitivities to the sulphites in wine in limited numbers of individuals, but the extent to which the sulphites contribute to wine sensitivity overall is not clear. The aetiology of wine-induced asthmatic responses may be complex and may involve several co-factors. PMID:12745410

  4. Asthmatic cough and airway oxidative stress.

    PubMed

    Koskela, Heikki O; Purokivi, Minna K; Nieminen, Riina M; Moilanen, Eeva

    2012-05-31

    The mechanisms of cough in asthma are unclear. Asthma is associated with an oxidative stress. Many reactive oxygen species sensitize or activate sensory C-fibers which are capable to induce cough. It was hypothesized that oxidative stress in the airways might contribute to the cough severity in asthma. Exhaled breath condensate samples were collected in ten healthy and 26 asthmatic subjects. The concentration of 8-isoprostane was measured. In addition, the subjects filled in Leicester Cough Questionnaire and underwent cough provocation tests with dry air hyperpnoea and hypertonic saline, among other measurements. Among the asthmatic subjects, high 8-isoprostane was associated with severe cough response to hyperpnoea (p=0.001), low Leicester Cough Questionnaire values (indicating severe subjective cough, p=0.02), and usage of combination asthma drugs (p=0.03-0.04). However, the 8-isoprostane concentrations did not differ significantly between the healthy and the asthmatic subjects. Airway oxidative stress may be associated with experienced cough severity and measured cough sensitivity in asthma. PMID:22546340

  5. Air pollution and cytokine responsiveness in asthmatic and non-asthmatic children.

    PubMed

    Klümper, Claudia; Krämer, Ursula; Lehmann, Irina; von Berg, Andrea; Berdel, Dietrich; Herberth, Gunda; Beckmann, Christina; Link, Elke; Heinrich, Joachim; Hoffmann, Barbara; Schins, Roel P F

    2015-04-01

    Epidemiological studies indicate that asthmatic children are more susceptible to traffic-related air pollution exposure than non-asthmatic children. Local and systemic inflammation in combination with oxidative stress have been suggested as a possible susceptibility factor. We investigated effect modification by asthma status for the association between air pollution exposure and systemic effects using whole blood cytokine responsiveness as an inflammatory marker. The study was nested within the two German birth cohort studies GINIplus and LISAplus and initially designed as a random sub-sample enriched with asthmatic children. Using data from 27 asthmatic and 59 non-asthmatic six-year-old children we measured the production of Interleukin-6 (IL)-6, IL-8, IL-10, monocyte chemotactic protein-1 (MCP-1), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in whole blood after ex-vivo stimulation with urban particulate matter (EHC-93). Air pollution exposure (nitrogen dioxide (NO2), nitrogen oxides (NOx), particulate matter with an aerodynamic diameter <10μm (PM10), particulate matter with an aerodynamic diameter <2.5μm (PM2.5mass), coarse particulate matter (PMcoarse) and PM2.5absorbance (PM2.5abs)) was modelled for children´s home addresses applying land-use regression. To assess effect modification by asthma status linear regression models with multiplicative interaction terms were used. In asthmatics exposure to NO2 was associated with higher production of pro-inflammatory cytokines: adjusted means ratio (MR) 2.22 (95% confidence interval 1.22-4.04) for IL-6 per 2.68µg/m³ NO2. The interaction term between asthma status and NO2 exposure was significant. Results for NOx, PM10, PM2.5mass and PM2.5abs were in the same direction. No association between air pollution and cytokine responsiveness was found in the group of non-asthmatic children and in the overall group. Traffic-related air pollution exposure is associated with higher pro

  6. Effect of inhaled furosemide and torasemide on bronchial response to ultrasonically nebulized distilled water in asthmatic subjects.

    PubMed

    Foresi, A; Pelucchi, A; Mastropasqua, B; Cavigioli, G; Carlesi, R M; Marazzini, L

    1992-08-01

    Inhaled furosemide has been shown to reduce the bronchoconstriction induced by several indirect stimuli, including ultrasonically nebulized distilled water (UNDW). Because the protective effect could be due to the inhibition of the Na(+)-2Cl(-)-K+ cotransport system of bronchial epithelium, we have compared the protective effect of inhaled furosemide with that of inhaled torasemide, a new and more potent loop diuretic, on UNDW-induced bronchoconstriction in a group of 12 asthmatic subjects. UNDW challenge was performed by constructing a stimulus-response curve with five increasing volume outputs of distilled water (from 0.5 to 5.2 ml/min) and the bronchial response expressed as the provocative output causing a 20% fall in FEV1 (PO20UNDW). On different days, each subject inhaled an equal dose (28 mg) of furosemide and torasemide in a randomized, double-blind, placebo-controlled study 5 min prior to an UNDW challenge. Furosemide and torasemide had no significant effect on resting lung function. The geometric mean value of PO20UNDW measured after placebo was 1.73 ml/min. This was significantly lower than that recorded after furosemide (4.25 ml/min; p < 0.025), but not after torasemide (3.05 ml/min; p = 0.07). Inhaled furosemide totally blocked bronchial response to UNDW in five subjects. In two of five subjects the response was also blocked by inhaled torasemide. A remarkable increase in diuresis was noted only after torasemide in most subjects. We conclude that inhaled furosemide has a better protective effect than does inhaled torasemide against UNDW-induced bronchoconstriction. However, the protective effect of furosemide is variable, with some asthmatic patients showing no change in bronchial response to UNDW.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1489126

  7. Rebamipide suppresses mite-induced asthmatic responses in NC/Nga mice.

    PubMed

    Murakami, Ikuo; Zhang, Ran; Kubo, Masayuki; Nagaoka, Kenjiro; Eguchi, Eri; Ogino, Keiki

    2015-10-15

    Allergic asthma caused by continuous allergen exposure evokes allergen-specific Th2 responses and is characterized by chronic airway inflammation and hyperresponsiveness. A previous report showed that rebamipide improved asthmatic symptoms in an ovalbumin/trypsin mice model. However, it is still unclear how rebamipide exerts its effects in asthma. In this study, rebamipide improved the asthmatic responses induced by mite exposure in NC/Nga mice, revealing the mechanism of this therapeutic effect. Rebamipide suppressed the infiltration of eosinophils into the airways and lung as well as attenuating the production of reactive oxygen species in tissues. In addition to these anti-inflammatory effects, rebamipide inhibited the production of IL-33, a member of the IL-1 family that drives the subsequent production of Th2-associated cytokines. These observations identify the point where rebamipide exerts its suppressive action on asthma and suggest that rebamipide has therapeutic potential in preventing mite-induced asthma. PMID:26472814

  8. Atopy and Inhaled Corticosteroid Use Associate with Fewer IL-17+ Cells in Asthmatic Airways

    PubMed Central

    Fattahi, Fatemeh; Brandsma, Corry-Anke; Lodewijk, Monique; Reinders-Luinge, Marjan; Postma, Dirkje S.; Timens, Wim; Hylkema, Machteld N.; ten Hacken, Nick H. T.

    2016-01-01

    Background Interleukin (IL)-17 plays a critical role in numerous immune and inflammatory responses and was recently suggested to contribute to the pathogenesis of nonatopic (non-eosinophil/neutrophil-dominant) asthma. We aimed to compare expression of IL-17 in bronchial airways between atopic and nonatopic asthmatics, with/without inhaled corticosteroid (ICS) use and to identify its major cellular source. Methods Bronchial biopsies from 114 patients with mild-to-moderate asthma were investigated: 33 nonatopic, 63 non-corticosteroid users, 90 nonsmokers. IL-17 expression was correlated with atopy and inflammatory cell counts (EPX, NP57, CD3, CD4, CD8, CD20, CD68), taking ICS use and smoking into account. Multiple linear regression analyses were used to determine the independent factors as well as the most relevant inflammatory cells contributing to IL-17 expression. Double immunostainings were performed to confirm the major cellular source of IL-17. Results In non-ICS users, nonatopic asthmatics had more IL-17+ cells in the airway wall than atopic asthmatics. In both atopic and nonatopic asthmatics, ICS use was associated with lower numbers of IL-17+ cells, independent of smoking. The number of IL-17+ cells was associated with the number of neutrophils (B: 0.26, 95% CI: 0.17–0.35) and eosinophils (B: 0.18, 95% CI: 0.07–0.29). The majority of IL-17+ cells were neutrophils, as confirmed by double immunostaining. Conclusions We show for the first time that atopy and ICS use are associated with lower numbers of IL-17+ cells in asthmatic airways. Importantly, IL-17+ cells were mostly neutrophils which conflicts with the paradigm that lymphocytes (Th17) are the main source of IL-17. PMID:27552197

  9. Asthmatics Exhibit Altered Oxylipin Profiles Compared to Healthy Individuals after Subway Air Exposure

    PubMed Central

    Nording, Malin; Klepczynska-Nyström, Anna; Sköld, Magnus; Haeggström, Jesper Z.; Grunewald, Johan; Svartengren, Magnus; Hammock, Bruce D.; Larsson, Britt-Marie; Eklund, Anders; Wheelock, Åsa M.; Wheelock, Craig E.

    2011-01-01

    Background Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM) and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications. Objectives This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air. Methods Sixty-four oxylipins representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of bronchoalveolar lavage (BAL)-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information. Results Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and α-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E2 (PGE2). Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change. Conclusions Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas. PMID:21897859

  10. Human airway musculature on a chip: an in vitro model of allergic asthmatic bronchoconstriction and bronchodilation.

    PubMed

    Nesmith, Alexander Peyton; Agarwal, Ashutosh; McCain, Megan Laura; Parker, Kevin Kit

    2014-10-21

    Many potential new asthma therapies that show promise in the pre-clinical stage of drug development do not demonstrate efficacy during clinical trials. One factor contributing to this problem is the lack of human-relevant models of the airway that recapitulate the tissue-level structural and functional phenotypes of asthma. Hence, we sought to build a model of a human airway musculature on a chip that simulates healthy and asthmatic bronchoconstriction and bronchodilation in vitro by engineering anisotropic, laminar bronchial smooth muscle tissue on elastomeric thin films. In response to a cholinergic agonist, the muscle layer contracts and induces thin film bending, which serves as an in vitro analogue for bronchoconstriction. To mimic asthmatic inflammation, we exposed the engineered tissues to interleukin-13, which resulted in hypercontractility and altered relaxation in response to cholinergic challenge, similar to responses observed clinically in asthmatic patients as well as in studies with animal tissue. Moreover, we reversed asthmatic hypercontraction using a muscarinic antagonist and a β-agonist which are used clinically to relax constricted airways. Importantly, we demonstrated that targeting RhoA-mediated contraction using HA1077 decreased basal tone, prevented hypercontraction, and improved relaxation of the engineered tissues exposed to IL-13. These data suggest that we can recapitulate the structural and functional hallmarks of human asthmatic musculature on a chip, including responses to drug treatments for evaluation of safety and efficacy of new drugs. Further, our airway musculature on a chip provides an important tool for enabling mechanism-based search for new therapeutic targets through the ability to evaluate engineered muscle at the levels of protein expression, tissue structure, and tissue function. PMID:25093641

  11. Acute quadriparesis in an asthmatic treated with atracurium.

    PubMed

    Tousignant, C P; Bevan, D R; Eisen, A A; Fenwick, J C; Tweedale, M G

    1995-03-01

    An 18-yr-old male asthmatic was paralyzed with atracurium for a period of seven days to facilitate mechanical pulmonary ventilation. After withdrawal of the muscle relaxant, train-of-four neuromuscular monitoring demonstrated rapid recovery of normal function. Three days later he developed acute quadriparesis without respiratory compromise. Electrophysiological studies showed normal conduction velocities, low compound muscle action potential amplitudes and evidence of denervation. Most cases of post-ventilatory weakness in the ICU involve the use of vecuronium and pancuronium. It has been suggested that the steroid nucleus in these muscle relaxants may be responsible. Our patient developed generalised weakness after treatment with atracurium, a benzylisoquinolinium muscle relaxant. Thus, it appears that the steroid nucleus of vecuronium and pancuronium is not essential in causing post-ventilatory weakness. PMID:7743575

  12. Epidermal Growth Factor Removal or Tyrphostin AG1478 Treatment Reduces Goblet Cells & Mucus Secretion of Epithelial Cells from Asthmatic Children Using the Air-Liquid Interface Model

    PubMed Central

    Parker, Jeremy C.; Douglas, Isobel; Bell, Jennifer; Comer, David; Bailie, Keith; Skibinski, Grzegorz; Heaney, Liam G.; Shields, Michael D.

    2015-01-01

    Rationale Epithelial remodelling in asthma is characterised by goblet cell hyperplasia and mucus hypersecretion for which no therapies exist. Differentiated bronchial air-liquid interface cultures from asthmatic children display high goblet cell numbers. Epidermal growth factor and its receptor have been implicated in goblet cell hyperplasia. Objectives We hypothesised that EGF removal or tyrphostin AG1478 treatment of differentiating air-liquid interface cultures from asthmatic children would result in a reduction of epithelial goblet cells and mucus secretion. Methods In Aim 1 primary bronchial epithelial cells from non-asthmatic (n = 5) and asthmatic (n = 5) children were differentiated under EGF-positive (10ng/ml EGF) and EGF-negative culture conditions for 28 days. In Aim 2, cultures from a further group of asthmatic children (n = 5) were grown under tyrphostin AG1478, a tyrosine kinase inhibitor, conditions. All cultures were analysed for epithelial resistance, markers of differentiation using immunocytochemistry, ELISA for MUC5AC mucin secretion and qPCR for MUC5AC mRNA. Results In cultures from asthmatic children the goblet cell number was reduced in the EGF negative group (p = 0.01). Tyrphostin AG1478 treatment of cultures from asthmatic children had significant reductions in goblet cells at 0.2μg/ml (p = 0.03) and 2μg/ml (p = 0.003) as well as mucus secretion at 2μg/ml (p = 0.04). Conclusions We have shown in this preliminary study that through EGF removal and tyrphostin AG1478 treatment the goblet cell number and mucus hypersecretion in differentiating air-liquid interface cultures from asthmatic children is significantly reduced. This further highlights the epidermal growth factor receptor as a potential therapeutic target to inhibit goblet cell hyperplasia and mucus hypersecretion in asthma. PMID:26057128

  13. Sensitization and exposure to pet allergens in asthmatics versus non-asthmatics with allergic rhinitis.

    PubMed

    Henriksen, A H; Holmen, T L; Bjermer, L

    2001-02-01

    In sensitized subjects with allergic rhinitis (AR) or asthma, allergen exposure provokes symptoms. Among non-asthmatics with AR, an association between allergen sensitization, pollen season and lower airway inflammation has been demonstrated. Our aims were to compare AR and asthma with regard to patterns of allergen sensitization, the degree of airway hyperresponsiveness (AHR) and levels of exhaled nitric oxide (ENO). Finally, we wanted to relate our findings to previous or current exposure to household pets. Four hundred and thirty-one adolescents with different clinical phenotypes were randomly selected from a large-scale epidemiological survey. They were investigated with allergy screening, measurements of ENO and a methacholine bronchoprovocation test. Sensitization to pet allergens (cat, dog and horse) was associated with increased AHR and ENO both in asthmatics and non-asthmatics with AR. The risk of being sensitized to cat allergens was significantly reduced in those who had kept cats vs. those who had never kept them. Keeping dogs or horses did not influence the risk of being sensitized to the respective allergens. Only in steroid-naive, non-smoking asthmatics, a trend towards increased ENO in those sensitized and exposed to cat or dog allergens was seen. Although sensitization towards pet allergens was associated with inflammation in the lower airways irrespective of clinical phenotype, keeping pets did not increase the risk of being sensitized to pet allergens. PMID:11217908

  14. Does eosinophil cationic protein in sputum and blood reflect bronchial inflammation and obstruction in allergic asthmatics?

    PubMed

    Grebski, E; Wu, J; Wüthrich, B; Medici, T C

    1999-01-01

    In the assessment of asthma severity and monitoring of asthma drug therapy, eosinophils and eosinophil cationic protein (ECP) have been identified in blood but rarely in sputum. The aim of our study was to determine if ECP concentrations in blood and sputum reflect bronchial inflammation and obstruction in allergic asthmatics and if inhaled steroids influence this relationship. We carried out a descriptive, cross-sectional study of 42 allergic asthmatic outpatients from a respiratory medicine department, of whom 22 were on beta 2-adrenergic agonists only and 20 were treated with low doses of inhaled steroids. Spirometry and methacholine challenge were performed and eosinophils and ECP values in induced sputum and blood were determined. The age and FEV1 were similar in both groups. It was found that in patients receiving inhaled steroids, the methacholine PD20 was higher than in patients on beta 2-adrenergic agonists only. However, there were no significant differences in serum and sputum ECP between the groups (median 14.5 micrograms/l vs. 17.2 micrograms/l and 235 micrograms/l vs. 301 micrograms/l, respectively). In patients not receiving steroids, sputum ECP correlated positively with eosinophils in sputum (r = 0.61, p < 0.01) and inversely with FEV1 (r = -0.43, p < 0.05). Serum ECP correlated with blood eosinophils and methacholine PD20. In patients treated with inhaled steroids most correlations were no longer significant. We concluded that ECP in sputum, rather than in blood, seems to reflect both eosinophilic inflammation and bronchial obstruction in asthmatics not receiving inhaled steroids. Asthmatics on low doses of inhaled steroids had increased ECP levels in sputum and serum, indicating persistent eosinophilic inflammation of the airways. PMID:10353094

  15. MANNITOL BRONCHIAL CHALLENGE TEST IN ASTHMATIC CHILDREN.

    PubMed

    Miraglia Del Giudice, M; Capristo, C; Decima, F; Coronella, A; Indolfi, C; Parisi, G; Maiello, N

    2015-01-01

    Bronchial asthma is a chronic inflammatory disease characterized by bronchial obstruction, usually reversible spontaneously or after therapy, bronchial hyperreactivity and accelerated decrease of lung function that may possibly evolve into irreversible obstruction of the respiratory tract. Bronchial provocation tests can be used in order to assess the presence and degree of bronchial hyper reactivity. The recently introduced mannitol powder inhalation indirect test seems to have an interesting and promising role, especially in childhood, because of its high diagnostic specificity, easiness of execution and best standardization. In this study the authors focused on the significance and clinical use of mannitol bronchial challenge test in asthmatic children. PMID:26634590

  16. CD4(+), CD25(+), FOXP3 (+) T Regulatory Cell Levels in Obese, Asthmatic, Asthmatic Obese, and Healthy Children.

    PubMed

    Donma, Metin; Karasu, Erkut; Ozdilek, Burcu; Turgut, Burhan; Topcu, Birol; Nalbantoglu, Burcin; Donma, Orkide

    2015-08-01

    The aim of this prospective case control study is to determine CD4(+), CD25(+), and FoxP3(+) T regulatory cells (Tregs) and T helper cells (Ths) in obese, asthmatic, asthmatic obese, and healthy children. Obese (n = 40), asthmatic (n = 40), asthmatic obese (n = 40), and healthy children (n = 40) were included in this study. Blood samples collected from children were marked with CD4, CD25, ve Foxp3 in order to detect Tregs and Ths by flow cytometric method. Statistical analyses were performed. p ≤ 0.05 was chosen as meaningful threshold. Tregs exhibiting anti-inflammatory nature were significantly lower in obese (0.16 %; p ≤ 0.001), asthmatic (0.25 %; p ≤ 0.01), and asthmatic obese (0.29 %; p ≤ 0.05) groups than control group (0.38 %). Ths were counted higher in asthma group than control (p ≤ 0.01) and obese (p ≤ 0.001) groups. T cell immunity plays important roles in chronic inflammatory diseases such as obesity and asthma pathogeneses. Decreased numbers of Tregs found in obese, asthmatic, and asthmatic obese children might represent a challenge of these cells. PMID:25655390

  17. Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics.

    PubMed

    Orsmark-Pietras, Christina; James, Anna; Konradsen, Jon R; Nordlund, Björn; Söderhäll, Cilla; Pulkkinen, Ville; Pedroletti, Christophe; Daham, Kameran; Kupczyk, Maciek; Dahlén, Barbro; Kere, Juha; Dahlén, Sven-Erik; Hedlin, Gunilla; Melén, Erik

    2013-07-01

    The causes of severe childhood asthma are poorly understood. Our aim was to define global patterns of gene expression in children with severe therapy-resistant and controlled asthma. White blood cells were isolated and the global transcriptome profile was characterised using the Affymetrix Human Gene ST 1.0 chip in children with severe, therapy-resistant asthma (n=17), controlled asthma (n=19) and healthy controls (n=18). Receptor expression was studied in separated leukocyte fractions from asthmatic adults (n=12). Overall, 1378 genes were differentially expressed between children with severe/controlled asthma and controls. Three significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways were represented: natural killer cell-mediated cytotoxicity (upregulated in controlled asthma); N-glycan biosynthesis (downregulated in severe asthma); and bitter taste transduction receptors (TAS2Rs) (upregulated in severe asthma). Quantitative PCR experiments confirmed upregulation of TAS2Rs in severe asthmatics. TAS2R expression was replicated in leukocytes from adult asthmatics, in which TAS2R agonists also inhibited LPS-induced cytokine release. Significant correlations between expression of TAS2Rs and clinical markers of asthma severity were found in both adults and children. In conclusion, specific gene expression patterns were observed in children with severe, therapy-resistant asthma. The increased expression of bronchodilatory TAS2Rs suggests a new target for the treatment of asthma. PMID:23222870

  18. Airborne particulate matter PM2.5 from Mexico City affects the generation of reactive oxygen species by blood neutrophils from asthmatics: an in vitro approach

    PubMed Central

    Sierra-Vargas, Martha Patricia; Guzman-Grenfell, Alberto Martin; Blanco-Jimenez, Salvador; Sepulveda-Sanchez, Jose David; Bernabe-Cabanillas, Rosa Maria; Cardenas-Gonzalez, Beatriz; Ceballos, Guillermo; Hicks, Juan Jose

    2009-01-01

    Background The Mexico City Metropolitan Area is densely populated, and toxic air pollutants are generated and concentrated at a higher rate because of its geographic characteristics. It is well known that exposure to particulate matter, especially to fine and ultra-fine particles, enhances the risk of cardio-respiratory diseases, especially in populations susceptible to oxidative stress. The aim of this study was to evaluate the effect of fine particles on the respiratory burst of circulating neutrophils from asthmatic patients living in Mexico City. Methods In total, 6 subjects diagnosed with mild asthma and 11 healthy volunteers were asked to participate. Neutrophils were isolated from peripheral venous blood and incubated with fine particles, and the generation of reactive oxygen species was recorded by chemiluminescence. We also measured plasma lipoperoxidation susceptibility and plasma myeloperoxidase and paraoxonase activities by spectrophotometry. Results Asthmatic patients showed significantly lower plasma paraoxonase activity, higher susceptibility to plasma lipoperoxidation and an increase in myeloperoxidase activity that differed significantly from the control group. In the presence of fine particles, neutrophils from asthmatic patients showed an increased tendency to generate reactive oxygen species after stimulation with fine particles (PM2.5). Conclusion These findings suggest that asthmatic patients have higher oxidation of plasmatic lipids due to reduced antioxidant defense. Furthermore, fine particles tended to increase the respiratory burst of blood human neutrophils from the asthmatic group. On the whole, increased myeloperoxidase activity and susceptibility to lipoperoxidation with a concomitant decrease in paraoxonase activity in asthmatic patients could favor lung infection and hence disrupt the control of asthmatic crises. PMID:19563660

  19. Urinary metabolomic profiling of asthmatics can be related to clinical characteristics.

    PubMed

    Loureiro, C C; Oliveira, A S; Santos, M; Rudnitskaya, A; Todo-Bom, A; Bousquet, J; Rocha, S M

    2016-09-01

    Metabolomics has been increasingly explored to achieve an improved understanding of asthma. In the current observational and exploratory study, the first to have examined the relationship between oxidative stress extension, eosinophilic inflammation, and disease severity in asthmatic patients, metabolomics (using target aliphatic aldehydes and alkanes) was carried out using solid-phase microextraction (SPME) followed by a comprehensive two-dimensional gas chromatography coupled to mass spectrometry with a high-resolution time-of-flight analyzer (GC×GC-ToFMS). We were able to demonstrate that metabolomics can give valuable insights into asthma mechanisms once lipidic peroxidation assessed by urinary metabolomics is related to the clinical characteristics of nonobese asthmatics, such as disease severity, lung function, and eosinophilic inflammation. Nevertheless, considering our sample size, the obtained results require further validation using a much larger sample cohort. PMID:27188766

  20. Salivary cortisol monitoring: determination of reference values in healthy children and application in asthmatic children.

    PubMed

    Nagakura, Toshikazu; Tanaka, Toshiaki; Arita, Masahiko; Nishikawa, Kiyoshi; Shigeta, Makoto; Wada, Noriyuki; Matsumoto, Tsutomu; Hiraba, Kazumi; Fukuda, Norimasa

    2012-01-01

    Venipuncture testing of adrenocortical function in asthmatic infants and young children receiving inhaled corticosteroids can raise cortisol levels and mask physiological responses. This study aimed to establish reference ranges for salivary cortisol levels and evaluate the safety and effects of jet-nebulized budesonide inhalation suspension (BIS) on salivary cortisol levels and patient outcomes in infants and young children with mild or persistent asthma. Reference salivary cortisol levels were determined in healthy children aged 6 months to 4 years old. A 12-week multicenter, randomized, parallel-group, open-label study was performed involving 53 age-matched asthmatic children who received either 0.5 mg/day of BIS or 40-60 mg/day of cromolyn sodium inhalation suspension (CIS) via compressor nebulizer. The effective measuring range of salivary cortisol concentration in asthmatic children was 0.12-3.00 micrograms/dL. The upper and lower limits of the reference range were 0.827 and 0.076 micrograms/dL, respectively. No significant difference was seen from baseline through week 12 in the CIS and BIS groups. BIS was safe in these patients, with no inhibitory effects on adrenocortical function. Salivary cortisol measurement offers a useful and accurate tool for testing adrenocortical function in infants and young children. Longer-term studies that incorporate testing of the hypothalamic-pituitary-adrenal axis are warranted to confirm our findings. PMID:22856637

  1. Expression of surface markers on the blood cells during the delayed asthmatic response to allergen challenge

    PubMed Central

    2014-01-01

    Patients with bronchial asthma develop various types of asthmatic response to bronchial challenge with allergen, such as immediate/early asthmatic response (IAR), late asthmatic response (LAR) or delayed asthmatic response (DYAR), because of different immunologic mechanisms. The DYAR, occurring between 24 and 56 hours after the bronchial allergen challenge (p < 0.01), differs from IAR and LAR in clinical as well as immunologic features. This study investigates the expression of CD molecules (markers) on the surface of particular cell populations in the peripheral blood and their changes during the DYAR. In 17 patients developing the DYAR (p < 0.01), the bronchial challenge with allergen was repeated 2–6 weeks later. The repeated DYAR (p < 0.001) was combined with recording of CD molecule expression on various types of blood cells by means of flow cytometry up to 72 hours after the challenge. The results were expressed in percent of the mean relative fluorescence intensity. The DYAR was accompanied by (a) increased expression of CD11b, CD11b/18, CD16,CD32, CD35, CD62E, CD62L, CD64, and CD66b on neutrophils; CD203C on basophils; CD25 and CD62L on eosinophils; CD14, CD16, CD64, and CD86 on monocytes; CD3, CD4, CD8, CD11a, CD18, and CD69 on lymphocytes; CD16, CD56, CD57, and CD94 on natural killer (NK) cells; and CD31, CD41, CD61, CD62P, and CD63 on thrombocytes and (b) decreased expression of CD18 and CD62L on eosinophils, CD15 on neutrophils, and CD40 on lymphocytes. These results suggest involvement of cell-mediated hypersensitivity mechanism, on participation of Th1- lymphocytes, neutrophils, monocytes, NK cells, and thrombocytes in the DYAR. PMID:24988283

  2. Insufficient platelet inhibition and thromboembolic complications in patients with intracranial aneurysms after stent placement.

    PubMed

    Yang, Hongchao; Li, Youxiang; Jiang, Yuhua

    2016-08-01

    OBJECT Insufficient platelet inhibition has been associated with an increased incidence of thromboembolic complications in cardiology patients undergoing percutaneous coronary intervention. Data regarding the relationship between insufficient platelet inhibition and thromboembolic complications in patients undergoing neurovascular procedures remain controversial. The purpose of this study was to assess the relationship of insufficient platelet inhibition and thromboembolic complications in patients with intracranial aneurysm undergoing stent treatment. METHODS The authors prospectively recruited patients with intracranial aneurysms undergoing stent treatment and maintained the data in a database. MRI with diffusion-weighted sequences was performed within 24 hours of stent insertion to identify acute ischemic lesions. The authors used thromboelastography to assess the degree of platelet inhibition in response to clopidogrel and aspirin. Univariate and multivariate logistic regression analysis was used to identify potential risk factors of thromboembolic complications. RESULTS One hundred sixty-eight patients with 193 aneurysms were enrolled in this study. Ninety-one of 168 (54.2%) patients with acute cerebral ischemic lesions were identified by diffusion-weighted MRI. In 9 (5.4%) patients with ischemic lesions, transient ischemic attack or stroke was found at discharge, and these complications were found in 11 (6.5%) patients during the follow-up period. The incidence of periprocedural thromboembolic complications increased with resistance to antiplatelet agents, hypertension, hyperlipidemia, complete occlusion, and aneurysm of the anterior circulation. The multivariate regression analysis demonstrated that the anterior circulation and adenosine diphosphate (ADP) inhibition percentage were independent risk factors of perioperative thromboembolic complications. The maximum amplitude and ADP inhibition percentage were independent risk factors for thromboembolic

  3. Effects of particulate air pollution on asthmatics

    SciTech Connect

    Perry, G.B.; Chai, H.; Dickey, D.W.; Jones, R.H.; Kinsman, R.A.; Morrill, C.G.; Spector, S.L.; Weiser, P.C.

    1983-01-01

    Twenty-four asthmatic subjects in Denver were followed from January through March 1979, a three-month period in which Denver air pollution levels are generally high and variable. Dichotomous, virtual impactor samplers provided daily measurements (micrograms/m3) of inhaled particulate matter (total mass, sulfates, and nitrates) for coarse (2.5--15 micrograms in aerodynamic diameter) and fine fractions (less than 2.5 micrometers). Carbon monoxide, sulfur dioxide, ozone, temperature, and barometric pressure were also measured. Twice daily measurements of each subject's peak expiratory flow rates, use of as-needed aerosolized bronchodilators, and report of airways obstruction symptoms characteristic of asthma were tested for relationships to air pollutants using a random effects model across subjects. During the time actually observed, there were very few days in which high levels of suspended particulates were recorded. Of the environmental variables studied, only fine nitrates were associated with increased symptom reports and increased aerosolized bronchodilator usage.

  4. Effect of natural grass pollen exposure on exhaled nitric oxide in asthmatic children.

    PubMed

    Baraldi, E; Carrá, S; Dario, C; Azzolin, N; Ongaro, R; Marcer, G; Zacchello, F

    1999-01-01

    Exhaled nitiric oxide (NO) is increased in exhaled breath of asthmatic patients. The aim of this study was to investigate the longitudinal changes of exhaled NO outside and during the pollen season in pollen-allergic asthmatic children. Twenty-one children (age 6 to 16 yr), with a seasonal allergic asthma sensitive to grass pollen, underwent measurements of exhaled NO and pulmonary function before (March), during (May), and after (November) the pollen season. Exhaled NO was measured by a tidal breathing method with a chemiluminescence analyzer and NO steady-state levels were recorded. The timing of the measurements during the pollen season was based on the atmospheric pollen count. Exhaled NO values of asthmatic children were compared with those of 21 sex- and age-matched healthy children. Pulmonary function and symptoms of asthma were also evaluated at each visit. The mean value of exhaled NO before the grass season was 12.7 +/- 5.1 ppb (mean +/- SD), significantly higher when compared with controls (7.8 +/- 2.7 ppb, p < 0.001). In the pollen season there was a significant (p < 0.001) twofold increase in exhaled NO (21.4 +/- 7.6 ppb) that, after the season, returned to values similar (12.8 +/- 5.8 ppb, p = NS) to those found before the season. There were no significant changes in FEV1 before and during the season (98.6% predicted versus 101% predicted, p = NS). We conclude that natural allergen exposure is related to an increase of exhaled NO in asthmatic grass pollen-allergic children even in absence of significant changes in airways function. We speculate that measurement of exhaled NO could be a sensitive noninvasive marker of asthma disease activity. PMID:9872848

  5. Traffic Pollution Tied to Preterm Birth Risk for Asthmatic Women

    MedlinePlus

    ... nih.gov/medlineplus/news/fullstory_157539.html Traffic Pollution Tied to Preterm Birth Risk for Asthmatic Women ... suggests. Both short- and long-term exposure to pollution from vehicles was linked to a higher risk ...

  6. Quantitative computed tomography–derived clusters: Redefining airway remodeling in asthmatic patients☆

    PubMed Central

    Gupta, Sumit; Hartley, Ruth; Khan, Umair T.; Singapuri, Amisha; Hargadon, Beverly; Monteiro, William; Pavord, Ian D.; Sousa, Ana R.; Marshall, Richard P.; Subramanian, Deepak; Parr, David; Entwisle, James J.; Siddiqui, Salman; Raj, Vimal; Brightling, Christopher E.

    2014-01-01

    Background Asthma heterogeneity is multidimensional and requires additional tools to unravel its complexity. Computed tomography (CT)–assessed proximal airway remodeling and air trapping in asthmatic patients might provide new insights into underlying disease mechanisms. Objectives The aim of this study was to explore novel, quantitative, CT-determined asthma phenotypes. Methods Sixty-five asthmatic patients and 30 healthy subjects underwent detailed clinical, physiologic characterization and quantitative CT analysis. Factor and cluster analysis techniques were used to determine 3 novel, quantitative, CT-based asthma phenotypes. Results Patients with severe and mild-to-moderate asthma demonstrated smaller mean right upper lobe apical segmental bronchus (RB1) lumen volume (LV) in comparison with healthy control subjects (272.3 mm3 [SD, 112.6 mm3], 259.0 mm3 [SD, 53.3 mm3], 366.4 mm3 [SD, 195.3 mm3], respectively; P = .007) but no difference in RB1 wall volume (WV). Air trapping measured based on mean lung density expiratory/inspiratory ratio was greater in patients with severe and mild-to-moderate asthma compared with that seen in healthy control subjects (0.861 [SD, 0.05)], 0.866 [SD, 0.07], and 0.830 [SD, 0.06], respectively; P = .04). The fractal dimension of the segmented airway tree was less in asthmatic patients compared with that seen in control subjects (P = .007). Three novel, quantitative, CT-based asthma clusters were identified, all of which demonstrated air trapping. Cluster 1 demonstrates increased RB1 WV and RB1 LV but decreased RB1 percentage WV. On the contrary, cluster 3 subjects have the smallest RB1 WV and LV values but the highest RB1 percentage WV values. There is a lack of proximal airway remodeling in cluster 2 subjects. Conclusions Quantitative CT analysis provides a new perspective in asthma phenotyping, which might prove useful in patient selection for novel therapies. PMID:24238646

  7. In utero exposure to second-hand smoke activates pro-asthmatic and oncogenic miRNAs in adult asthmatic mice.

    PubMed

    Xiao, Rui; Noël, Alexandra; Perveen, Zakia; Penn, Arthur L

    2016-04-01

    Exposures to environmental pollutants contribute to dysregulated microRNA (miRNA) expression profiles, which have been implicated in various diseases. Previously, we reported aggravated asthmatic responses in ovalbumin (OVA)-challenged adult mice that had been exposed in utero to second-hand smoke (SHS). Whether in utero SHS exposure dysregulates miRNA expression patterns in the adult asthma model has not been investigated. Pregnant BALB/c mice were exposed (days 6-19 of pregnancy) to SHS (10 mg/m(3)) or HEPA-filtered air. All offspring were sensitized and challenged with OVA (19-23 weeks) before sacrifice. RNA samples extracted from lung homogenates, were subjected to RNA sequencing (RNA-seq). RNA-seq identified nine miRNAs that were most significantly up-regulated by in utero SHS exposure. Among these nine, miR-155-5p, miR-21-3p, and miR-18a-5p were also highly correlated with pro-asthmatic Th2 cytokine levels in bronchoalveolar lavage fluid. Further analysis indicated that these up-regulated miRNAs shared common chromosome locations, particularly Chr 11C, with pro-asthmatic genes. These three miRNAs have also been characterized as oncogenic miRNAs (oncomirs). We cross-referenced miRNA-mRNA expression profiles and identified 16 tumor suppressor genes that were down-regulated in the in utero-exposed offspring and that are predicted targets of the up-regulated oncomirs. In conclusion, in utero SHS exposure activates pro-asthmatic genes and miRNAs, which colocalize at specific chromosome locations, in OVA-challenged adult mice. The oncogenic characteristics of the miRNAs and putative miRNA-mRNA regulatory networks suggest that the synergistic effect of in utero SHS exposure and certain adult irritants may promote an oncogenic milieu in mouse lungs via inhibition of miRNA-regulated tumor suppressor genes. PMID:26859758

  8. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug

    PubMed Central

    Marschallinger, Julia; Schäffner, Iris; Klein, Barbara; Gelfert, Renate; Rivera, Francisco J.; Illes, Sebastian; Grassner, Lukas; Janssen, Maximilian; Rotheneichner, Peter; Schmuckermair, Claudia; Coras, Roland; Boccazzi, Marta; Chishty, Mansoor; Lagler, Florian B.; Renic, Marija; Bauer, Hans-Christian; Singewald, Nicolas; Blümcke, Ingmar; Bogdahn, Ulrich; Couillard-Despres, Sebastien; Lie, D. Chichung; Abbracchio, Maria P.; Aigner, Ludwig

    2015-01-01

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood–brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias. PMID:26506265

  9. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug.

    PubMed

    Marschallinger, Julia; Schäffner, Iris; Klein, Barbara; Gelfert, Renate; Rivera, Francisco J; Illes, Sebastian; Grassner, Lukas; Janssen, Maximilian; Rotheneichner, Peter; Schmuckermair, Claudia; Coras, Roland; Boccazzi, Marta; Chishty, Mansoor; Lagler, Florian B; Renic, Marija; Bauer, Hans-Christian; Singewald, Nicolas; Blümcke, Ingmar; Bogdahn, Ulrich; Couillard-Despres, Sebastien; Lie, D Chichung; Abbracchio, Maria P; Aigner, Ludwig

    2015-01-01

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood-brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias. PMID:26506265

  10. Problems Inhibiting Attentional Capture by Irrelevant Stimuli in Patients with Frontotemporal Dementia

    ERIC Educational Resources Information Center

    Piquard, Ambre; Lacomblez, Lucette; Derouesne, Christian; Sieroff, Eric

    2009-01-01

    We studied the role of the frontal lobes in orienting spatial attention and inhibiting attentional capture by goal-irrelevant stimuli, using a spatial cueing method in patients with frontotemporal dementia (FTD). Two blocks of trials were presented, one with non-predictive cues and the other with counter-predictive cues. FTD patients showed a…

  11. Salicylic acid derivatives as potential anti asthmatic agents using disease responsive drug delivery system for prophylactic therapy of allergic asthma.

    PubMed

    Raju, Kalidhindi Rama Satyanarayana; Ambhore, Nilesh S; Mulukutla, Shashank; Gupta, Saurabh; Murthy, Vishakantha; Kumar, M N Kiran; Madhunapantula, Subba Rao V; Kuppuswamy, Gowthamarajan; Elango, Kannan

    2016-02-01

    Asthma is a multi-factorial and complicated lung disorder of the immune system which has expanded to a wider ambit unveiling its etiology to be omnipresent at both ends of the spectrum involving basic pharmacology and in-depth immunology. As asthma occurs through triggered activation of various immune cells due to different stimuli, it poses a great challenge to uncover specific targets for therapeutic interventions. Recent pharmacotherapeutic approaches for asthma have been focused on molecular targeting of transcription factors and their signaling pathways; mainly nucleus factor kappa B (NFκB) and its associated pathways which orchestrate the synthesis of pro-inflammatory cytokines (IL-1β, TNF-α, GM-CSF), chemokines (RANTES, MIP-1a, eotaxin), adhesion molecules (ICAM-1, VCAM-1) and inflammatory enzymes (cyclooxygenase-2 and iNOS). 5-aminosalicylic acid (5-ASA) and sodium salicylate are known to suppress NFκB activation by inhibiting inhibitor of kappa B kinase (IKκB). In order to target the transcription factor, a suitable carrier system for delivering the drug to the intracellular space is essential. 5-ASA and sodium salicylate loaded liposomes incorporated into PEG-4-acrylate and CCRGGC microgels (a polymer formed by crosslinking of trypsin sensitive peptide and PEG-4-acrylate) could probably suit the needs for developing a disease responsive drug delivery system which will serve as a prophylactic therapy for asthmatic patients. PMID:26643666

  12. Role and Significance of Markers of Inflammation in the Asthmatic Disease

    PubMed Central

    Goseva, Zlatica; Janeva, Elena Jovanovska; Gjorcev, Angelko; Arsovski, Zoran; Pejkovska, Sava

    2015-01-01

    BACKGROUND: Asthma is characterized by airway inflammation which can be reversible. AIM: Investigation the importance of eosinophils, ECP and IL-5 in asthmatics versus patients with obstructive bronchitis and healthy subjects. We investigated the values before and after the treatment in asthmatics. MATERIAL AND METHODS: We studied 77 subjects divided in three groups as follows: 1) asthma patients; 2) patients with obstructive bronchitis and 3) control group of healthy subjects. In all the subjects there were determined: Total number of eosinophils (Eo), eosinophilic cationic protein (ECP), Interleukin 5 (IL-5) and allergy tests. RESULTS: The total number of eosinophils was significantly increased in the group of asthma patients versus second and third group. We found that the presence of ECP demonstrate an ongoing inflammation, with or without clinical symptoms of asthma patients. There was significant difference between the values of ECP of asthma patients versus second and third group. Our results have shown that IL-5 was significantly increased versus second group and controls (p < 0.01). We also found the decrease of the values of inflammatory markers after the treatment with corticosteroids. CONCLUSIONS: Eosinophils, ECP and IL-5 could be useful markers for selecting allergic patients and could be the monitors of treatment effects. PMID:27275299

  13. The Efficacy and Safety of Antiinterleukin 13, a Monoclonal Antibody, in Adult Patients With Asthma

    PubMed Central

    Luo, Jian; Liu, Dan; Liu, Chun-Tao

    2016-01-01

    Abstract Effects of antiinterleukin 13 therapies in patients with asthma remain inconsistent. Therefore, we aimed to further clarify the efficacy and safety of antiinterleukin 13 therapies in adult asthmatics by a systematic review and meta-analysis. Randomized controlled trials which reported pulmonary functions, fraction of exhaled nitric oxide (FeNO), Asthma Control Questionnaire (ACQ), rescue use of short-acting-β-agonist (SABA), and rate of asthmatic exacerbation and adverse events were identified in Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), American College of Physician (ACP) Journal Club, and ISI Web of Science, reference lists and by manual searches. Randomized-effect models were used in meta-analysis to calculate pooled mean difference and relative risks (RR). Eight studies with 957 patients were enrolled. Systematic review showed that treatment with antiinterleukin 13 antibodies could significantly improve peak expiratory flow (PEF), decrease FeNO and asthmatic exacerbation, but could not decrease blood and sputum eosinophil levels, improve FEV1, inhibit methacholine PC20, or reduce ACQ scores. Two studies reported opposite results in reducing rescue use of SABA. Meta-analysis showed that antiinterleukin 13 monoclonal therapies could significantly decrease asthmatic exacerbation (RR 0.55, 95% CI: 0.31–0.96, z = 2.10, P = 0.04), but did not significantly improve the FEV1 (95% CI: −1.03 to 2.22, z = 0.72, P = 0.47) or increasing adverse events (RR 1.00, 95% CI: 0.91–1.10, z = 0.00, P = 1.00). Antiinterleukin 13 monoclonal therapies could be safely used to improve PEF, decrease FeNO and asthmatic exacerbation, and probably reduce rescue use of SABA, but could not decrease blood and sputum eosinophil levels, improve FEV1, inhibit methacholine PC20, or reduce ACQ scores. PMID:26871775

  14. [Two cases of asthmatic attack caused by spinal anesthesia].

    PubMed

    Kawabata, K M

    1996-01-01

    Case 1: A 26-year-old primipara, underwent emergency cesarean section because of premature rupture of membrane and breech presentation in her 36th week of gestation. She had no history of asthma, but physical examination revealed atopic dermatitis in the neck and the arms. Case 2: A 21-year-old woman underwent removal of ovarian cyst. She had a history of asthma in her childhood. On physical examination there was no abnormal findings. For both cases spinal anesthesia was uneventfully induced using 2 and 3 ml of 0.4% tetracaine in 10% dextrose respectively. Sensory loss to cold extended to T3 in both cases. Immediately after the anesthesia reached two level, the first patient began to cough and the second patient complained of difficulty in breathing, and then both became dyspneic in 10-15 minutes thereafter. Wheezing rhonchi was audible in both cases. Both patients recovered fully with antiasthmatic therapy. There was no shock, nor change of the skin and the mucosa. The baby also had no problem postoperatively. Skin reaction to intradermal injection of 0.025 ml of 0.4-0.00004% tetracaine in normal saline was tested on two patients and on eleven volunteers. At higher concentrations it resulted in positive in the patients and all the volunteers, and at lower concentrations it resulted in positive in case 2 and under-positive in case 1 and three volunteers having histories of allergic disease. Skin testing alone does not offer any diagnostic of tetracaine allergy, because tetracaine might be a chemical irritant. Thoracic adrenergic nerve blockade due to spinal anesthesia might trigger asthmatic attack by influencing the cholinergic ganglia of the lung and/or pulmonary blood flow. PMID:8965338

  15. Choline magnesium trisalicylate in patients with aspirin-induced asthma.

    PubMed

    Szczeklik, A; Nizankowska, E; Dworski, R

    1990-05-01

    Treatment of inflammatory diseases of asthmatics can be a serious problem since some patients show intolerance to aspirin and other non-steroidal, anti-inflammatory drugs that are cyclooxygenase inhibitors. Salicylates were believed to be well tolerated, but recent reports have demonstrated that diflunisal and salicylsalicylic acid can precipitate asthma attacks in aspirin-intolerant patients. This study was designed to determine the tolerance of choline magnesium trisalicylate (CMT), a nonacetylated salicylate with potent analgesic and anti-inflammatory activity, in 23 asthmatics with aspirin hypersensitivity confirmed by oral challenge. The study consisted of three phases: 1) patients received increasing doses (50-1,500 mg) of CMT under a single-blind protocol; 2) patients received either a placebo or CMT challenge in a double-blind, randomized, cross-over design; 3) patients received CMT at daily 3,000 mg doses for 1 week. Throughout the study, pulmonary function tests, peak nasal inspiratory flow, and serum salicylate and thromboxane B2 (TXB2) levels were monitored. Results showed no airway obstruction, nasal congestion or rhinorrhea after CMT. There was no significant decrease in serum TXB2 levels, indicating the absence of cyclooxygenase inhibition with CMT. We conclude that choline magnesium trisalicylate is a safe drug for treatment of different anti-inflammatory disorders in asthmatics with aspirin hypersensitivity. PMID:2198165

  16. Oral health status in preschool asthmatic children in Iran.

    PubMed

    Ehsani, Sara; Moin, Mostafa; Meighani, Ghasem; Pourhashemi, Seyed Jalal; Khayatpisheh, Hadi; Yarahmadi, Nazli

    2013-09-01

    Asthma is a chronic inflammatory disorder of the airways, which is diagnosed by periodic symptoms of inflammation, bronchial spasm, and increased mucosal secretions. It has higher incidence among the preschool children. There are many contradictory reports based on the effect of asthma on oral health, however it has been hypothesized that asthma could lead to poor oral health. The objective of the present study was to investigate oral health indices in 44 preschool children of three to six years old with mild to moderate asthma and 46 matched healthy children in Tehran Children's Respiratory Center. Dental plaque, gingival inflammation, mouth breathing, and dental caries were evaluated by one trained examiner according to World Health Organization [WHO] criteria. Culture and colony counting of streptococcus mutans and lactobacillus species were carried out in saliva specimens of the patients. The effects of different factors on the colony counts were statistically analyzed using linear regression analysis. The level of mother's education and preexisting asthma disease in children had significant effect on the colony counts of streptococcus species whereas no factor was found to influence the number of lactobacillus counts significantly. The results indicated no significant differences between the children with asthma and those without asthma regarding (decayed, missing, filled, teeth) dmft index (mean of 3.34 in asthmatic children and 3.0 in the control group). Therefore, it can be deduced that the presence of asthma disease did not increase the probability of tooth decay. PMID:23893809

  17. Increased amount of nitric oxide in exhaled air of asthmatics.

    PubMed

    Alving, K; Weitzberg, E; Lundberg, J M

    1993-10-01

    The presence of nitric oxide (NO) in the exhaled air of humans has recently been described. We wanted to assess at what level exhaled NO originates in normal airways, and to determine whether airway inflammation induces changes in the levels of exhaled NO. Exhaled NO was continuously measured by chemiluminescence technique during normal tidal breathing through the nose or mouth, with a detection limit of 1 part per billion (ppb). Twelve control subjects were compared to eight patients with mild atopic asthma and rhinitis caused by occupational allergen. In control subjects, the major part of NO in exhaled air (up to 30 ppb) seemed to originate in the nasal airways, with only minor contribution from the lower airways and the oral cavity. However, in mild asthmatics, the level of exhaled NO during oral breathing, indicating the involvement of the lower airways, was increased 2-3 fold. Since increased production of NO in the lower airways may involve activated macrophages or neutrophils, we suggest that exhaled NO may be used to instantly monitor ongoing bronchial inflammation, at least when involving inducible NO synthase. PMID:7507065

  18. Anti-asthmatic activities of an ethanol extract of Aster yomena in an ovalbumin-induced murine asthma model.

    PubMed

    Sim, Ji Hyun; Lee, Hyun Seung; Lee, Sunkyung; Park, Dae Eun; Oh, Keunhee; Hwang, Kyung-A; Kang, Hye-Ryun; Ye, Sang-Kyu; Kim, Hang-Rae

    2014-05-01

    Aster yomena is used in traditional remedies to treat cough, asthma and insect bites; however, its therapeutic mechanism is not completely understood. To elucidate the anti-asthmatic effect of A. yomena, we investigated the anti-asthmatic characteristics of an alcohol extract of A. yomena in an ovalbumin (OVA)-induced murine asthma model. In this study, we showed that A. yomena extract inhibited the overall pathophysiological features of asthma by suppressing Th2 responses and enzymes associated with the production of inflammatory mediators. This suppression resulted in decreased Th2 type cytokines and eosinophils in the bronchoalveolar lavage fluid and OVA-specific IgE in serum. Additionally, A. yomena extract significantly decreased airway hyperresponsiveness and abrogated the histopathological changes in the lungs, which reached normal levels in the OVA-challenged mice treated with A. yomena extract. These findings suggest that A. yomena could be a promising natural agent for treating bronchial asthma in humans. PMID:24738663

  19. Parenting asthmatic children: identification of parenting challenges.

    PubMed

    Morawska, Alina; Stelzer, Jennifer; Burgess, Scott

    2008-08-01

    Asthma is the most common chronic illness of childhood, affecting up to 14% of children. Poor asthma management and non-adherence to treatment regimens are a pervasive problem in this population and are related to exacerbation of symptoms. Effective management of pediatric asthma involves a complex set of interactions between the parent and child, yet there is a paucity of literature examining these interactions. The main purpose of this study was to identify the child behavior and asthma management tasks parents experience difficulty with. It was hypothesized that the more asthma behavior problems reported, the more problems parents experience in asthma management tasks. Participants in this study were 255 parents of 2-to 10-year-old asthmatic children, recruited via an advertisement placed in school newsletters throughout Australia. Results indicated that the most problematic child asthma behaviors were oppositional behavior, hyperactivity, and aggression, and anxiety was also identified by parents as a concern. The main problematic asthma parenting tasks were entrusting the school, entrusting caregivers, identifying unique symptoms, and identifying and avoiding triggers. More problem asthma behaviors were associated with higher levels of parenting difficulty and more general levels of behavior problems. Parents who reported more dysfunctional parenting styles reported more difficulties with their child's asthma behavior. Based on the results it is suggested that an appropriate parenting intervention program would target basic behavioral management skills, in addition to applying these behavior management principles to asthma management. PMID:18612898

  20. FoxO1 regulates allergic asthmatic inflammation through regulating polarization of the macrophage inflammatory phenotype

    PubMed Central

    Chung, Sangwoon; Lee, Tae Jin; Reader, Brenda F.; Kim, Ji Young; Lee, Yong Gyu; Park, Gye Young; Karpurapu, Manjula; Ballinger, Megan N.; Qian, Feng; Rusu, Luiza; Chung, Hae Young; Unterman, Terry G.; Croce, Carlo M.; Christman, John W.

    2016-01-01

    Inflammatory monocyte and tissue macrophages influence the initiation, progression, and resolution of type 2 immune responses, and alveolar macrophages are the most prevalent immune-effector cells in the lung. While we were characterizing the M1- or M2-like macrophages in type 2 allergic inflammation, we discovered that FoxO1 is highly expressed in alternatively activated macrophages. Although several studies have been focused on the fundamental role of FoxOs in hematopoietic and immune cells, the exact role that FoxO1 plays in allergic asthmatic inflammation in activated macrophages has not been investigated. Growing evidences indicate that FoxO1 acts as an upstream regulator of IRF4 and could have a role in a specific inflammatory phenotype of macrophages. Therefore, we hypothesized that IRF4 expression regulated by FoxO1 in alveolar macrophages is required for established type 2 immune mediates allergic lung inflammation. Our data indicate that targeted deletion of FoxO1 using FoxO1-selective inhibitor AS1842856 and genetic ablation of FoxO1 in macrophages significantly decreases IRF4 and various M2 macrophage-associated genes, suggesting a mechanism that involves FoxO1-IRF4 signaling in alveolar macrophages that works to polarize macrophages toward established type 2 immune responses. In response to the challenge of DRA (dust mite, ragweed, and Aspergillus) allergens, macrophage specific FoxO1 overexpression is associated with an accentuation of asthmatic lung inflammation, whereas pharmacologic inhibition of FoxO1 by AS1842856 attenuates the development of asthmatic lung inflammation. Thus, our study identifies a role for FoxO1-IRF4 signaling in the development of alternatively activated alveolar macrophages that contribute to type 2 allergic airway inflammation. PMID:27007158

  1. Early patterns of wheezing in asthmatic and nonasthmatic children.

    PubMed

    Cano Garcinuño, Alfredo; Mora Gandarillas, Isabel

    2013-10-01

    The aim of this study was to describe the time patterns of wheezing in both asthmatic and nonasthmatic children during the first 36 months of life, and to determine whether there are asthma-related breakpoints in the incidence of wheezing. Data from a historical cohort of children followed from birth to 6 years (SLAM cohort) were used. Wheezing episodes until 36 months and asthma at 6 years were both recorded by a doctor. Monthly mean incidence rate of wheezing and rate ratio were calculated. Joinpoint regression models were built to identify breakpoints in the risk of wheeze. Complete information was available for 3739 children. Wheezing in the first 36 months was more frequent in asthmatic than in nonasthmatic children (rate ratio 2.62, 95% CI 1.81-3.78). Differences were appreciable within the first months and increased steadily thereafter because of a persistently high rate in asthmatic children. No breakpoint in the rate ratio could be identified. Asthmatic children exhibited a one-phase curve of incidence and nonasthmatic children exhibited a two-phase curve. However, children with allergic asthma also displayed a two-phase curve. There is no identifiable breakpoint during the first 36 months of life at which the incidence of wheezing in asthmatic children begins to stand out. PMID:23349448

  2. A survey of daily asthmatic activity patterns in Cincinnati

    SciTech Connect

    Not Available

    1992-11-01

    A survey was undertaken in Cincinnati to obtain information on the activity patterns of asthmatics. Because studies have demonstrated symptomatic responses to elevated levels of SO[sub 2] only during outdoor exercise, information on the behavioral patterns of asthmatics is vital for the accurate estimation of risk due to air pollution exposures. In particular, data detailing the actual likelihood of asthmatics being engaged in strenuous outdoor activity at any given time of day is essential for an accurate appraisal of response probability. This, in turn, is necessary for an accurate estimate of risk. In the absence of such activity data, those concerned with the setting of short-term SO[sub 2] regulations are required to use purely subjective judgment to estimate how many asthmatics are engaged in strenuous outdoor exercise when SO[sub 2] levels are high enough to affect them. The activity pattern data give an indication of how much such an assumption would overestimate the true response and thus the true risk associated with SO[sub 2]. Lack of information on the activity patterns of asthmatics has thus been a critical gap in the SO[sub 2] risk assessment process. The primary purpose of this survey was to fill that gap.

  3. In vitro inhibition of CYP3A4 by herbal remedies frequently used by cancer patients.

    PubMed

    Engdal, Silje; Nilsen, Odd Georg

    2009-07-01

    The herbal remedies Natto K2, Agaricus, mistletoe, noni juice, green tea and garlic, frequently used by cancer patients, were investigated for their in vitro inhibition potential of cytochrome P-450 3A4 (CYP3A4) metabolism. To our knowledge, only garlic and green tea had available data on the possible inhibition of CYP3A4 metabolism. Metabolic studies were performed with human c-DNA baculovirus expressed CYP3A4. Testosterone was used as a substrate and ketoconazole as a positive quantitative inhibition control. The formation of 6-beta-OH-testosterone was quantified by a validated HPLC methodology. Green tea was the most potent inhibitor of CYP3A4 metabolism (IC(50): 73 microg/mL), followed by Agaricus, mistletoe and noni juice (1324, 3594, >10 000 microg/mL, respectively). All IC(50) values were high compared with those determined for crude extracts of other herbal remedies. The IC(50)/IC(25) ratios for the inhibiting herbal remedies ranged from 2.15 to 2.67, indicating similar inhibition profiles of the herbal inhibitors of CYP3A4. Garlic and Natto K2 were classified as non-inhibitors. Although Agaricus, noni juice, mistletoe and green tea inhibited CYP3A4 metabolism in vitro, clinically relevant systemic or intestinal interactions with CYP3A4 were considered unlikely, except for a probable inhibition of intestinal CYP3A4 by the green tea product. PMID:19170155

  4. Association of School Social Networks’ Influence and Mass Media Factors With Cigarette Smoking Among Asthmatic Students

    PubMed Central

    Kanamori, Mariano; Beck, Kenneth H.; Carter-Pokras, Olivia

    2015-01-01

    BACKGROUND Around 10% of adolescent students under 18 years have current asthma. Asthmatic adolescents smoke as much or more than non-asthmatic adolescents. We explored the association between exposure to mass media and social networks’ influence with asthmatic student smoking, and variations of these exposures by sex. METHODS This study included 9755 asthmatic and 38,487 non-asthmatic middle and high school students. Secondary data analysis incorporated the complex sample design; and univariate, bivariate, and logistic regression statistics. RESULTS Asthmatic students had greater odds of smoking than non-asthmatic students. Asthmatic female students were more likely than asthmatic male students to have been exposed to secondhand smoke in rooms or cars and to smoking actors, but less likely to associate smoking with intent to wear tobacco-marketing products, or with looking cool/fitting in. Asthmatic male and female students, who have smoking friends, were exposed to secondhand smoke in rooms (only girls) or cars, intended to smoke if best friends offered cigarettes, or received/bought tobacco marketing products had greater odds of smoking than other asthmatic students. CONCLUSIONS The observed associations suggest the need for general interventions to reduce middle and high school students’ cigarette smoking as well as targeted interventions for asthmatic adolescent students. PMID:25611937

  5. SOCS3 Silencing Attenuates Eosinophil Functions in Asthma Patients

    PubMed Central

    Zafra, Mª Paz; Cañas, Jose A.; Mazzeo, Carla; Gámez, Cristina; Sanz, Veronica; Fernández-Nieto, Mar; Quirce, Santiago; Barranco, Pilar; Ruiz-Hornillos, Javier; Sastre, Joaquín; del Pozo, Victoria

    2015-01-01

    Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process. PMID:25764157

  6. SOCS3 silencing attenuates eosinophil functions in asthma patients.

    PubMed

    Zafra, Ma Paz; Cañas, Jose A; Mazzeo, Carla; Gámez, Cristina; Sanz, Veronica; Fernández-Nieto, Mar; Quirce, Santiago; Barranco, Pilar; Ruiz-Hornillos, Javier; Sastre, Joaquín; del Pozo, Victoria

    2015-01-01

    Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process. PMID:25764157

  7. Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients

    PubMed Central

    Zimerman, Máximo; Wessel, Maximilian J.; Timmermann, Jan E.; Granström, Sofia; Gerloff, Christian; Mautner, Victor F.; Hummel, Friedhelm C.

    2015-01-01

    Background Cognitive difficulties are the most common neurological complications in neurofibromatosis type 1 (NF1) patients. Recent animal models proposed increased GABA-mediated inhibition as one underlying mechanism directly affecting the induction of long-term potentiation (LTP) and learning. In most adult NF1 patients, apparent cognitive and attentional deficits, tumors affecting the nervous system and other confounding factors for neuroscientific studies are difficult to control for. Here we used a highly specific group of adult NF1 patients without cognitive or nervous system impairments. Such selected NF1 patients allowed us to address the following open questions: Is the learning process of acquiring a challenging motor skill impaired in NF1 patients? And is such an impairment in relation to differences in intracortical inhibition? Methods We used an established non-invasive, double-pulse transcranial magnetic stimulation (dp-TMS) paradigm to assess practice-related modulation of intracortical inhibition, possibly mediated by gamma-minobutyric acid (GABA)ergic-neurotransmission. This was done during an extended learning paradigm in a group of NF1 patients without any neuropsychological deficits, functioning normally in daily life and compared them to healthy age-matched controls. Findings NF1 patients experienced substantial decline in motor skill acquisition (F = 9.2, p = 0.008) over five-consecutives training days mediated through a selective reduction in the early acquisition (online) and the consolidation (offline) phase. Furthermore, there was a consistent decrease in task-related intracortical inhibition as a function of the magnitude of learning (T = 2.8, p = 0.014), especially evident after the early acquisition phase. Interpretations Collectively, the present results provide evidence that learning of a motor skill is impaired even in clinically intact NF1 patients based, at least partially, on a GABAergic-cortical dysfunctioning as

  8. Adherence to preventive medications in asthmatic children at a tertiary care teaching hospital in Malaysia

    PubMed Central

    Md Redzuan, Adyani; Lee, Meng Soon; Mohamed Shah, Noraida

    2014-01-01

    Purpose Asthma affects an estimated 300 million people worldwide. Poor adherence to prescribed preventive medications, especially among children with asthma, leads to increased mortality and morbidity. The purpose of this study was to assess the adherence and persistence levels of asthmatic children at the Universiti Kebangsaan Malaysia Medical Center (UKMMC), a tertiary care teaching hospital, and to determine the factors that influence adherence to prescribed preventive medications. Patients and methods Participants were asthmatic patients aged 18 years and younger with at least one prescription for a preventive medication refilled between January and December 2011. Refill records from the pharmacy dispensing database were used to determine the medication possession ratio (MPR) and continuous measure of gaps (CMG), measures of adherence and persistence levels, respectively. Results The sample consisted of 218 children with asthma from the General and Respiratory pediatric clinics at UKMMC. The overall adherence level was 38% (n=83; MPR ≥80%), and the persistence level was 27.5% (n=60; CMG ≤20%). We found a significant association between the adherence and persistence levels (r=0.483, P<0.01). The presence of comorbidities significantly predicted the adherence (odds ratio [OR] =16.21, 95% confidence interval [CI]: 7.76–33.84, P<0.01) and persistence level (OR =2.63, 95% CI: 0.13–52.79, P<0.01). Other factors, including age, sex, ethnicity, duration of asthma diagnosis, and number of prescribed preventive medications did not significantly affect adherence or persistence (P>0.05). Conclusion In conclusion, the adherence level among children with asthma at UKMMC was low. The presence of comorbidities was found to influence adherence towards preventive medications in asthmatic children. PMID:24600208

  9. A PITFALL IN THE CYTODIAGNOSIS OF SPUTUM OF ASTHMATICS.

    PubMed

    NAYLOR, B; RAILEY, C

    1964-01-01

    The sputum of an asthmatic often contains large, well-circumscribed clusters of benign columnar epithelial cells which can be misinterpreted as papillary fragments of an adenocarcinoma. Their presence is a manifestation of the excessive shedding of the mucosa of the lower respiratory tract accompanying an attack of bronchial asthma. These clusters are illustrated and compared with clusters of adenocarcinoma cells. To discriminate between the two types of cluster may be difficult and it is therefore important for the cytologist to know when a sputum is from an asthmatic. PMID:14100011

  10. A pitfall in the cytodiagnosis of sputum of asthmatics

    PubMed Central

    Naylor, Bernard; Railey, Constantine

    1964-01-01

    The sputum of an asthmatic often contains large, well-circumscribed clusters of benign columnar epithelial cells which can be misinterpreted as papillary fragments of an adenocarcinoma. Their presence is a manifestation of the excessive shedding of the mucosa of the lower respiratory tract accompanying an attack of bronchial asthma. These clusters are illustrated and compared with clusters of adenocarcinoma cells. To discriminate between the two types of cluster may be difficult and it is therefore important for the cytologist to know when a sputum is from an asthmatic. Images PMID:14100011

  11. Dyphylline aerosol can induce bronchospasm in human asthmatics.

    PubMed

    Lawyer, C; Auer, S; Brottem, J; Bardana, E; Hirshman, C; Lynn, R; Downes, H

    1982-01-01

    Dihydroxypropyl theophylline (dyphylline) was administered by aerosol in a single dose of 250 mg aerosolized over five minutes to two asthmatic volunteers and in a single dose of 375 mg aerosolized over ten minutes to two other asthmatic volunteers. Serial spirometry was then performed. Marked bronchospasm occurred within ten minutes in two of the subjects, and developed more slowly in another. One subject demonstrated no significant change. Aerosolized dyphylline solution was not an effective bronchodilator, using the methods described in this study. PMID:6957527

  12. Investigation of the anti-asthmatic activity of Oridonin on a mouse model of asthma

    PubMed Central

    Wang, Jing; Li, Fengsen; Ding, Jianbing; Tian, Ge; Jiang, Min; Gao, Zhen; Tuyghun, Ehbal

    2016-01-01

    Oridonin is an extract obtained from a traditional Chinese medicinal herb, Xihuangcao. Previous studies have demonstrated that Oridonin exerts various pharmaceutical effects, such as anti-tumor and immunosuppressive effects, as well as modulating cytokine balance. The present study identified that Oridonin could regulate the Th1/Th2 cytokine balance in mice. However, as the anti-asthmatic effect of Oridonin is currently unknown a mouse model of asthma was used in the present study. BALB/c mice were sensitized using ovalbumin (OVA), then the sensitized mice were treated with Oridonin prior to OVA challenge. The in vivo study indicated that Oridonin decreased the OVA-induced airway hyper-responsiveness significantly (P<0.05). In addition, the results indicated that in Oridonin-treated mice, the eosinophil number and total inflammatory cell number in bronchoalveolar lavage (BAL) fluid decreased significantly in the Oridonin group when compared with the control group. Further study indicated that Oridonin significantly decreased the level of inflammatory cytokines, which were induced by OVA, in BAL fluid. Histological studies were performed to evaluate the effect of Oridonin on eosinophilia and mucus in the airway, the results indicated that Oridonin significantly inhibited the eosinophilia and mucus production in the lungs. Therefore the present study demonstrated that Oridonin regulates Th1/Th2 balance in mice and exhibited anti-asthmatic effects in a mouse model of asthma. These findings indicate that Oridonin may serve as a potential therapeutic compound for the treatment of asthma in future. PMID:27431862

  13. Investigation of the anti‑asthmatic activity of Oridonin on a mouse model of asthma.

    PubMed

    Wang, Jing; Li, Fengsen; Ding, Jianbing; Tian, Ge; Jiang, Min; Gao, Zhen; Tuyghun, Ehbal

    2016-09-01

    Oridonin is an extract obtained from a traditional Chinese medicinal herb, Xihuangcao. Previous studies have demonstrated that Oridonin exerts various pharmaceutical effects, such as anti‑tumor and immunosuppressive effects, as well as modulating cytokine balance. The present study identified that Oridonin could regulate the Th1/Th2 cytokine balance in mice. However, as the anti‑asthmatic effect of Oridonin is currently unknown a mouse model of asthma was used in the present study. BALB/c mice were sensitized using ovalbumin (OVA), then the sensitized mice were treated with Oridonin prior to OVA challenge. The in vivo study indicated that Oridonin decreased the OVA‑induced airway hyper‑responsiveness significantly (P<0.05). In addition, the results indicated that in Oridonin‑treated mice, the eosinophil number and total inflammatory cell number in bronchoalveolar lavage (BAL) fluid decreased significantly in the Oridonin group when compared with the control group. Further study indicated that Oridonin significantly decreased the level of inflammatory cytokines, which were induced by OVA, in BAL fluid. Histological studies were performed to evaluate the effect of Oridonin on eosinophilia and mucus in the airway, the results indicated that Oridonin significantly inhibited the eosinophilia and mucus production in the lungs. Therefore the present study demonstrated that Oridonin regulates Th1/Th2 balance in mice and exhibited anti‑asthmatic effects in a mouse model of asthma. These findings indicate that Oridonin may serve as a potential therapeutic compound for the treatment of asthma in future. PMID:27431862

  14. Subthalamic nucleus activity dissociates proactive and reactive inhibition in patients with Parkinson's disease.

    PubMed

    Benis, Damien; David, Olivier; Lachaux, Jean-Philippe; Seigneuret, Eric; Krack, Paul; Fraix, Valérie; Chabardès, Stéphan; Bastin, Julien

    2014-05-01

    Models of action selection postulate the critical involvement of the subthalamic nucleus (STN), especially in reactive inhibition processes when inappropriate responses to a sudden stimulus must be overridden. The STN could also play a key role during proactive inhibition, when subjects prepare to potentially suppress their actions. Here, we hypothesized that STN responses to reactive and proactive inhibitory control might be driven by different underlying mechanisms with specific temporal profiles. Direct neural recordings in twelve Parkinson's disease patients during a modified stop signal task (SST) revealed a decrease of beta band activity (βA, 13-35Hz) in the STN during reactive inhibition of smaller amplitude and shorter duration than during motor execution. Crucially, the onset latency of this relative increase of βA took place before the stop signal reaction time. It could thus be thought of as a "stop" signal inhibiting thalamo-cortical activity that would have supported motor execution. Finally, results also revealed a higher level of βA in the STN during proactive inhibition, which correlated with patient's inhibitory performances. We propose that βA in the STN would here participate in the implementation of a "hold your horse" signal to delay motor responses, thus prioritizing accuracy as compared to speed. In brief, our results provide strong electrophysiological support for the hypothesized role of the STN during executive control underlying proactive and reactive response suppression. PMID:24368260

  15. Effect of interleukin-5 receptor-alpha short hairpin RNA-expressing vector on bone marrow eosinophilopoiesis in asthmatic mice.

    PubMed

    Mao, Hui; Wen, Fu-Qiang; Liu, Chun-Tao; Liang, Zong-An; Wang, Zeng-Li; Yin, Kai-Sheng

    2006-01-01

    Bone marrow eosinophilopoiesis induced by interleukin (IL)-5 is a major contributor to eosinophilic airway inflammation in asthma. However,research on the use of IL-5 receptor alpha (IL-5Ralpha) as the target has seldom been reported. This study was undertaken to explore the effects of inhibition of IL-5Ralpha expression through an IL-5Ralpha short hairpin RNA-expressing vector on bone marrow eosinophilopoiesis and airway inflammation in an asthmatic mouse model. An effective plasmid vector was selected that could express short hairpin RNA targeted at IL-5Ralpha (P-IL-5Ralpha). An adenovirus vector (Ad) was then constructed that was inserted in an effective template sequence (Ad-IL-5Ralpha). An animal model of asthma was established by sensitizing and challenging Balb/c mice with ovalbumin. Animals were treated intravenously with Ad-IL-5Ra and changes in bone marrow eosinophilopoiesis and airway inflammation were detected in asthmatic mice. Investigators found that P-IL-5Ra-3 targeted at the sequence of CAG CTG CCT GGT TCG TCT T markedly suppressed IL-5Ralpha expression in B lymphoma cells in vitro. In addition, Ad-IL-5Ralpha could suppress IL-5Ralpha expression in murine bone marrow cells in vitro and in vivo, and it could significantly decrease IL-5-induced eosinophilia in cultured bone marrow cells. Additional studies indicated that intravenously injected Ad-IL-5Ralpha not only selectively reduced the number of eosinophils in the bone marrow, peripheral blood, and bronchoalveolar lavage fluid, it also relieved airway inflammation in asthmatic mice. Results reported here show that blocking of IL-5Ralpha expression through RNA interference can enhance effective treatment of asthma, and that bone marrow can be used as a key targeted organ in the treatment of asthmatic mice. PMID:17276963

  16. Serum of patients with active rheumatoid arthritis inhibits differentiation of osteochondrogenic precursor cells.

    PubMed

    Pathak, Janak L; Verschueren, Patrick; Lems, Willem F; Bravenboer, Nathalie; Klein-Nulend, Jenneke; Bakker, Astrid D; Luyten, Frank P

    2016-05-01

    Delayed fracture healing is frequently experienced in patients with systemic inflammation such as during rheumatoid arthritis (RA). The reasons for this are diverse, but could also be caused by inflammatory cytokines and/or growth factors in serum from patients with active disease. We hypothesized that serum from patients with active RA contains circulating inflammatory factors that inhibit differentiation of osteochondrogenic precursors. Serum was obtained from 15 patients with active RA (active RA-sera) and from the same patients in clinical remission 1 year later (remission RA-sera; controls). The effect of active RA-sera on osteochondrogenic differentiation of chondrogenic ATDC5 cells and primary human periosteum-derived progenitor cells (HPDC) was determined in micromass culture. In ATDC5 cells, active RA-sera reduced Ki67 transcription levels by 40% and cartilage matrix accumulation by 14% at day 14, and Alp transcription levels by 16%, and matrix mineralization by 17% at day 21 compared with remission RA-sera. In HPDCs, active RA-sera inhibited metabolic activity by 8%, SOX9 transcription levels by 14%, and cartilage matrix accumulation by 7% at day 7 compared with remission RA-sera. In conclusion, sera from patients with active RA negatively affect differentiation of osteochondrogenic precursors, and as a consequence may contribute to delayed fracture healing in these patients. PMID:27050327

  17. EXPOSURE ASSESSMENT FINDINGS FROM THE TAMPA ASTHMATIC CHILDREN'S STUDY (TACS)

    EPA Science Inventory

    The Tampa Asthmatic Children's Study (TACS) was a pilot study that focused on developing and evaluating air pollution exposure assessment methods and participant recruiting tools. The four-week study was performed in October and November, 2003. The study involved repeated daily...

  18. Bronco Junction Proves Asthmatic Kids Can Live Active Lives.

    ERIC Educational Resources Information Center

    Foster, Scarlett Lee

    1980-01-01

    Camp Bronco Junction combines physical development, medical self-care knowledge, and fun in its eight-week program for asthmatic youngsters. In this environment, children are able to undertake activities that were formerly thought beyond their physical or emotional capabilities. (CJ)

  19. PRELIMINARY EXPOSURE ASSESSMENT FINDINGS FROM THE TAMPA ASTHMATIC CHILDREN'S STUDY

    EPA Science Inventory

    The Tampa Asthmatic Children's Study (TACS) was a pilot study that focused on developing and evaluating air pollution exposure assessment methods and participant recruiting tools. The four-week study was performed in October and November, 2003. The study involved repeated daily...

  20. ASCORBID ACID IS DECREASED IN INDUCED SPUTUM OF MILD ASTHMATICS

    EPA Science Inventory

    ABSTRACT
    Evidence suggests that the antioxidant ascorbic acid (AA), plays an essential role in defending against oxidant attack in the airways. Decreased levels of AA have been reported in asthmatics but not at the site directly proximal to asthma pathology, i.e. the bronchial...

  1. PILOT STUDY: THE TAMPA ASTHMATIC CHILDREN'S STUDY (TACS)

    EPA Science Inventory

    The Tampa Asthmatic Children's Study (TACS) was a pilot research study that focused on developing and evaluating air pollution exposure assessment methods and participant recruiting tools for children in the age range of 1-5 years old. The pilot study focused on (a) simple, cost-...

  2. ENVIRONMENTAL EXPOSURES IN RURAL IOWA HOMES WITH ASTHMATIC CHILDREN

    EPA Science Inventory

    ENVIRONMENTAL EXPOSURES IN RURAL IOWA HOMES WITH ASTHMATIC CHILDREN
    Erik R. Svendsen*?, Stephen J. Reynolds*?, James A. Merchant*, Ann M. Stromquist*, Peter S. Thorne*. * The University of Iowa College of Public Health, Iowa City, IA ?Current: USEPA,RTP, NC ?Current: Colorado...

  3. Functional networks of motor inhibition in conversion disorder patients and feigning subjects.

    PubMed

    Hassa, Thomas; de Jel, Esther; Tuescher, Oliver; Schmidt, Roger; Schoenfeld, Mircea Ariel

    2016-01-01

    The neural correlates of motor inhibition leading to paresis in conversion disorder are not well known. The key question is whether they are different of those of normal subjects feigning the symptoms. Thirteen conversion disorder patients with hemiparesis and twelve healthy controls were investigated using functional magnetic resonance tomography under conditions of passive motor stimulation of the paretic/feigned paretic and the non-paretic hand. Healthy controls were also investigated in a non-feigning condition. During passive movement of the affected right hand conversion disorder patients exhibited activations in the bilateral triangular part of the inferior frontal gyri (IFG), with a left side dominance compared to controls in non-feigning condition. Feigning controls revealed for the same condition a weak unilateral activation in the right triangular part of IFG and an activity decrease in frontal midline areas, which couldn't be observed in patients. The results suggest that motor inhibition in conversion disorder patients is mediated by the IFG that was also involved in inhibition processes in normal subjects. The activity pattern in feigning controls resembled that of conversion disorder patients but with a clear difference in the medial prefrontal cortex. Healthy controls showed decreased activity in this region during feigning compared to non-feigning conditions suggesting a reduced sense of self-agency during feigning. Remarkably, no activity differences could be observed in medial prefrontal cortex for patients vs healthy controls in feigning or non-feigning conditions suggesting self-agency related activity in patients to be in between those of non-feigning and feigning healthy subjects. PMID:27330971

  4. Novel celastrol derivatives inhibit the growth of hepatocellular carcinoma patient-derived xenografts.

    PubMed

    Wei, Wei; Wu, Song; Wang, Xiaolin; Sun, Chris Kin-Wai; Yang, Xiaoyang; Yan, Xinrui; Chua, Mei-Sze; So, Samuel

    2014-07-30

    The molecular co-chaperone CDC37 is over-expressed in hepatocellular carcinoma (HCC) cells, where it functions with HSP90 to regulate the activity of protein kinases in multiple oncogenic signaling pathways that contribute towards hepatocarcinogenesis. Disruption of these signaling pathways via inhibition of HSP90/CDC37 interaction is therefore a rational therapeutic approach. We evaluated the anti-tumor effects of celastrol, pristimerin, and two novel derivatives (cel-D2, and cel-D7) on HCC cell lines in vitro and on orthotopic HCC patient-derived xenografts in vivo. All four compounds preferentially inhibited viability of HCC cells in vitro,and significantly inhibited the growth of three orthotopic HCC patient-derived xenografts in vivo; with the novel derivatives cel-D2 and cel-D7 exhibiting lower toxicity. All four compounds also induced cell apoptosis; and promoted degradation and inhibited phosphorylation of protein kinases in the Raf/MEK/ERK and PI3K/AKT/mTOR signaling pathways. We demonstrated that HSP90/CDC37 antagonists are potentially broad spectrum agents that might be beneficial for treating the heterogeneous subtypes of HCC, either as monotherapy, or in combination with other chemotherapeutic agents. PMID:25051375

  5. Herbal Medicines for Asthmatic Inflammation: From Basic Researches to Clinical Applications

    PubMed Central

    Xuan, Nan-Xia; Ying, Song-Min; Li, Wen

    2016-01-01

    Asthma is one of the most common chronic inflammatory disorders, associated with reversible airflow obstruction, airway hyperresponsiveness, and airway remodeling. This disease has a significant impact on individuals, their families, and society. Standardized therapeutics such as inhaled corticosteroid in combination with long acting β2 agonist have been applied for asthma control; however, complementary and alternative medicines, especially herbal medicines, are still widely used all over the world. A growing body of literature suggests that various herbals or related products might be effective in inhibiting asthmatic inflammation. In this review, we summarize recent advances about the mechanistic studies of herbal medicines on allergic airway inflammation in animal models and their potential application into clinic for asthma control. PMID:27478309

  6. Monoamine oxidase inhibition prevents mitochondrial dysfunction and apoptosis in myoblasts from patients with collagen VI myopathies

    PubMed Central

    Sorato, E.; Menazza, S.; Zulian, A.; Sabatelli, P.; Gualandi, F.; Merlini, L.; Bonaldo, P.; Canton, M.; Bernardi, P.; Di Lisa, F.

    2014-01-01

    Although mitochondrial dysfunction and oxidative stress have been proposed to play a crucial role in several types of muscular dystrophy (MD), whether a causal link between these two alterations exists remains an open question. We have documented that mitochondrial dysfunction through opening of the permeability transition pore plays a key role in myoblasts from patients as well as in mouse models of MD, and that oxidative stress caused by monoamine oxidases (MAO) is involved in myofiber damage. In the present study we have tested whether MAO-dependent oxidative stress is a causal determinant of mitochondrial dysfunction and apoptosis in myoblasts from patients affected by collagen VI myopathies. We find that upon incubation with hydrogen peroxide or the MAO substrate tyramine myoblasts from patients upregulate MAO-B expression and display a significant rise in reactive oxygen species (ROS) levels, with concomitant mitochondrial depolarization. MAO inhibition by pargyline significantly reduced both ROS accumulation and mitochondrial dysfunction, and normalized the increased incidence of apoptosis in myoblasts from patients. Thus, MAO-dependent oxidative stress is causally related to mitochondrial dysfunction and cell death in myoblasts from patients affected by collagen VI myopathies, and inhibition of MAO should be explored as a potential treatment for these diseases. PMID:25017965

  7. Mangiferin Attenuates Th1/Th2 Cytokine Imbalance in an Ovalbumin-Induced Asthmatic Mouse Model

    PubMed Central

    Hou, Guang-Han; Du, Jun; Huang, Xin; Lu, Yi; Keller, Evan T.; Zhang, Jian; Deng, Jia-Gang

    2014-01-01

    Mangiferin is a major bioactive ingredient in Mangifera indica Linn. (Anacardiaceae) leaves. Aqueous extract of such leaves have been used as an indigenous remedy for respiratory diseases like asthma and coughing in traditional Chinese medicine. However, underlying molecular mechanisms of mangiferin on anti-asthma remain unclear. In our present study, we investigated the anti-asthmatic effect of mangiferin on Th1/Th2 cytokine profiles and explored its underlying immunoregulatory mechanism in mouse model of allergic asthma. Mangiferin significantly reduced the total inflammatory cell counts and eosinophil infiltration, decreased the production of ovalbumin-specific IgE in serum and PGD2 in BALF. The antibody array analysis showed that mangiferin down-regulated the levels of one group of cytokines/chemokines including Th2-related IL-4, IL-5, IL-13, and others IL-3, IL-9, IL-17, RANTES, TNF-α, but simultaneously up-regulated Th1-related IFN-γ, IL-2 and IL-10 and IL-12 expression in serum. Thus it attenuates the imbalance of Th1/Th2 cells ratio by diminishing the abnormal mRNA levels of Th1 cytokines (IFN-γ and IL-12) and Th2 cytokines (IL-4, IL-5 and IL-13). Finally, mangiferin substantially inhibited the activation and expression of STAT-6 and GATA-3 in excised lung tissues. Our results suggest that mangiferin can exert anti-asthmatic effect. The underlying mechanism may attribute to the modulation of Th1/Th2 cytokine imbalance via inhibiting the STAT6 signaling pathway. PMID:24955743

  8. Analysis of the masticatory process of asthmatic children: Clinical and electromyographic research

    PubMed Central

    da Cunha, Daniele Andrade; da Silva, Hilton Justino; Nascimento, Gerlane Karla Bezerra Oliveira; da Silva, Elthon Gomes Fernandes; da Cunha, Renata Andrade; Régis, Renata Milena Freire Lima; de Castro, Célia Maria Machado Barbosa

    2012-01-01

    Summary Introduction: The prevalence of asthma has grown considerably in recent decades, but some studies have shown stabilization of this trend. The masticatory process of asthmatic children may be altered due to asthma-related anatomo-functional changes. Objective: The study objective was to determine the clinical and electromyographic characteristics of the masticatory process in asthmatic children and compare the electrical activities of their masseter and anterior temporal muscles (at rest and during maximal voluntary contraction and mastication) with those of non-asthmatic children. Method: Case study. Asthmatic and non-asthmatic groups, each consisting of 30 children of both sexes between 6 and 10 years of age, were evaluated. Mastication was evaluated clinically and electromyographically in all subjects. RESULTS: The masticatory process did not differ significantly between asthmatic and non-asthmatic children. Conclusion: Although the masticatory process did not differ significantly between asthmatic and non-asthmatic children, the masticatory process of asthmatic children may be altered because of anatomical changes of Asthma. PMID:25991958

  9. Mucolytics for Intubated Asthmatic Children: A National Survey of United Kingdom Paediatric Intensive Care Consultants

    PubMed Central

    Snoek, Aarjan Peter; Brierley, Joe

    2015-01-01

    Aim. The extent to which mucolytics are utilised in mechanically ventilated asthmatic children is unknown. We sought to establish current practice in the United Kingdom (UK) including choice of mucolytic, dose, and frequency of utilisation. Methods. A national electronic survey was distributed to UK consultants during April and May 2014. We were able to identify 168 PICU consultants at 25 institutions to whom we were able to electronically distribute a survey, representing an estimated 81% of UK NHS PICU consultants. Results. Replies were received from 87 consultants at 21 institutions (response rate = 52%). Recombinant human DNase (rhDNase) does get administered by 63% of clinicians, with 54% and 19% that administer hypertonic saline or N-acetylcysteine, respectively. Of those that do administer rhDNase the majority (48%) dilute it with 0.9% saline and blindly administer it, whereas 35% administer rhDNase under bronchoscopic guidance and 17% judge the necessity for bronchoscopy according to clinical severity. 25 respondents described 7 different methods to calculate rhDNase dose. A majority (87%) of respondents expressed an interest to consider enrolling patients into an RCT that evaluates rhDNase. Conclusion. Significant variation exists regarding the necessity for mucolytics, choice of agent, optimal route, and dose in intubated asthmatic children. PMID:25722885

  10. A Mixed Methods Feasibility Trial of PKCι Inhibition with Auranofin in Asymptomatic Patients with Ovarian Cancer

    PubMed Central

    Jatoi, Aminah; Breitkopf, Carmen Radecki; Foster, Nathan R.; Block, Matthew S.; Grudem, Megan; Hendrickson, Andrea Wahner; Carlson, Rachel E.; Barrette, Brigitte; Karlin, Nina; Fields, Alan P.

    2015-01-01

    Purpose This trial was undertaken to 1) determine the feasibility of enrolling asymptomatic ovarian cancer patients with Ca-125 elevation to a trial with the PKCι inhibitor, auranofin, and 2) understand patients’ perceptions of Ca-125 monitoring. Methods Asymptomatic ovarian cancer patients with Ca-125 elevation received auranofin 3 mg orally twice/day and were evaluated. Patients participated in interviews about Ca-125 monitoring. Results Ten patients were enrolled in slightly over 6 months, exceeding our anticipated rate. Four manifested stable Ca-125 levels for 1 month or longer. The median progression-free survival was 2.8 months (95% confidence interval: 1.3, 3.8 months); auranofin was well tolerated. One patient had baseline and monthly Ca-125 levels of 5570, 6085, 3511, and 2230 units/mL, respectively, stopped auranofin because of radiographic progression at 3 months, and manifested an increase in Ca-125 to 7168 units/mL approximately 3 months later. Patient interviews revealed: 1) the important role of Ca-125 in cancer monitoring; 2) ardent advocacy for Ca-125 testing; and 3) evolution toward the Ca-125 assuming a life of its own. Conclusions This study showed feasibility; and patients favored Ca-125 monitoring. One patient had a decline in Ca-125, suggesting that PKCι inhibition merits further study in ovarian cancer. PMID:25502607

  11. Clinical evolution and nutritional status in asthmatic children and adolescents enrolled in Primary Health Care

    PubMed Central

    Morishita, Rosinha Yoko Matsubayaci; Strufaldi, Maria Wany Louzada; Puccini, Rosana Fiorini

    2015-01-01

    Objective: To evaluate the clinical evolution and the association between nutritional status and severity of asthma in children and adolescents enrolled in Primary Health Care. Methods: A retrospective cohort study of 219 asthmatic patients (3-17 years old) enrolled in Primary Care Services (PCSs) in Embu das Artes (SP), from 2007 to 2011. Secondary data: gender, age, diagnosis of asthma severity, other atopic diseases, family history of atopy, and body mass index. To evaluate the clinical outcome of asthma, data were collected on number of asthma exacerbations, number of emergency room consultations and doses of inhaled corticosteroids at follow-up visits in the 6th and 12th months. The statistical analysis included chi-square and Kappa agreement index, with 5% set as the significance level. Results: 50.5% of patients started wheezing before the age of 2 years, 99.5% had allergic rhinitis and 65.2% had a positive family history of atopy. Regarding severity, intermittent asthma was more frequent (51.6%) and, in relation to nutritional status, 65.8% of patients had normal weight. There was no association between nutritional status and asthma severity (p=0.409). After 1 year of follow-up, 25.2% of patients showed reduction in exacerbations and emergency room consultations, and 16.2% reduced the amount of inhaled corticosteroids. Conclusions: The monitoring of asthmatic patients in Primary Care Services showed improvement in clinical outcome, with a decreased number of exacerbations, emergency room consultations and doses of inhaled corticosteroids. No association between nutritional status and asthma severity was observed in this study. PMID:26316387

  12. Inhibition of adenovirus DNA synthesis in vitro by sera from patients with systemic lupus erythematosus

    SciTech Connect

    Horwitz, M.S.; Friefeld, B.R.; Keiser, H.D.

    1982-12-01

    Sera containing antinuclear antibodies from patients with systemic lupus erythematosus (SLE) and related disorders were tested for their effect on the synthesis of adenovirus (Ad) DNA in an in vitro replication system. After being heated at 60/sup 0/C for 1 h, some sera from patients with SLE inhibited Ad DNA synthesis by 60 to 100%. Antibodies to double-stranded DNA were present in 15 of the 16 inhibitory sera, and inhibitory activity copurified with anti-double-stranded DNA in the immunoglobulin G fraction. These SLE sera did not inhibit the DNA polymerases ..cap alpha.., BETA, ..gamma.. and had no antibody to the 72,000-dalton DNA-binding protein necessary for Ad DNA synthesis. The presence of antibodies to single-stranded DNA and a variety of saline-extractable antigens (Sm, Ha, nRNP, and rRNP) did not correlate with SLE serum inhibitory activity. Methods previously developed for studying the individual steps in Ad DNA replication were used to determine the site of inhibition by the SLE sera that contained antibody to double-stranded DNA. Concentrations of the SLE inhibitor that decreased the elongation of Ad DNA by greater than 85% had no effect on either the initiation of Ad DNA synthesis or the polymerization of the first 26 deoxyribonucleotides.

  13. Cross-reactivity between aspirin and ibuprofen in an asthmatic--a case report.

    PubMed

    Merritt, G J; Selle, R I

    1978-10-01

    A case of an adverse reaction occurring in a 53-year-old, aspirin-sensitive asthmatic male with nasal polyps following administration of a 400-mg ibuprofen tablet is reported. Symptoms of the adverse reaction included an urticarial rash, labored breathing, laryngeal edema and tightness of the chest. Treatment consisted of isoproterenol inhalant (self-administered), subcutaneous epinephrine 0.25 mg, intramuscular diphenhydramine hydrochloride 50 mg and intravenous hydrocortisone 250 mg. The pathogenesis of the patient's adverse reaction and the possible fole of aspirin, of other analgesics and of tartrazine in its development are discussed. The adverse reaction was not mediated immunologically but rather resulted from the prostaglandin synthetase (PGS)-inhibitor activity shared by aspirin, ibuprofen and other analgesics. Selection of an analgesic for an aspirin-sensitive patient should be based on the analgesic's PGS-inhibitor activity. PMID:696734

  14. Glycoxidized HDL, HDL enriched with oxidized phospholipids and HDL from diabetic patients inhibit platelet function

    PubMed Central

    Lê, Quang Huy; El Alaoui, Meddy; Véricel, Evelyne; Ségrestin, Bérénice; Soulère, Laurent; Guichardant, Michel; Lagarde, Michel; Moulin, Philippe; Calzada, Catherine

    2015-01-01

    Context High-density lipoproteins (HDL) possess atheroprotective properties including anti-thrombotic and antioxidant effects. Very few studies relate to the functional effects of oxidized HDL on platelets in type 2 diabetes (T2D). Objective The objective of our study was to investigate the effects of in vitro glycoxidized HDL, and HDL from T2D patients on platelet aggregation and arachidonic acid signaling cascade. At the same time, the contents of hydroxylated fatty acids were assessed in HDL. Results Compared to control HDL, in vitro glycoxidized HDL had decreased proportions of linoleic (LA) and arachidonic (AA) acids in phospholipids and cholesteryl esters, and increased concentrations of hydroxy-octadecadienoic acids (9-HODE and 13-HODE) and 15-hydroxy-eicosatetraenoic acid (15-HETE), derived from LA and AA respectively, especially hydroxy derivatives esterified in phospholipids. Glycoxidized HDL dose-dependently decreased collagen-induced platelet aggregation by binding to SR-BI. Glycoxidized HDL prevented collagen-induced increased phosphorylation of platelet p38 MAPK and cytosolic phospholipase A2, as well as intracellular calcium mobilization. HDL enriched with oxidized phospholipids, namely PC(16:0/13-HODE) dose-dependently inhibited platelet aggregation. Increased concentrations of 9-HODE, 13-HODE and 15-HETE in phospholipids (2.1, 2.1 and 2.4-fold increase respectively) were found in HDL from patients with T2D, and these HDL also inhibited platelet aggregation via SR-BI. Conclusions Altogether, our results indicate that in vitro glycoxidized HDL as well as HDL from T2D patients inhibit platelet aggregation, and suggest that oxidized LA-containing phospholipids may contribute to the anti-aggregatory effects of glycoxidized HDL and HDL from T2D patients. PMID:25794249

  15. Immune responses to final exams in healthy and asthmatic adolescents.

    PubMed

    Kang, D H; Coe, C L; McCarthy, D O; Ershler, W B

    1997-01-01

    Immune responses to an academic stressor were examined in healthy and asthmatic adolescents with regard to their illness symptom reports. Eighty-seven high school students completed a health diary for 2 weeks and provided three blood samples during midsemester, final-exam, and postexam periods. During exam week, all students showed significant immunological alterations from baseline. Natural killer cell activity was significantly lower, whereas lymphocyte proliferation and neutrophil superoxide release were significantly higher. These immune changes tended to return toward baseline during the postexam period, but the enhanced neutrophil reactivity continued to rise. Overall, immunological responses were similar between asthmatic subjects and controls. Appropriate medical management may have accounted for this similarity. However, subtle group differences in the postexam recovery pattern and a continuous activation of inflammatory cell function following a stressor may warrant further investigation. PMID:9024419

  16. Unsweetened natural cocoa has anti-asthmatic potential.

    PubMed

    Awortwe, C; Asiedu-Gyekye, I J; Nkansah, E; Adjei, S

    2014-01-01

    Unsweetened natural cocoa powder is enriched with nutraceutical abundance of anti-asthmatic compounds theobromine and theophylline. Cocoa powder, which is prepared after removal of the cocoa butter, contains about 1.9% theobromine and 0.21% caffeine. Anecdotal reports indicate that regular consumption of unsweetened natural cocoa powder (UNCP), a common practice in Ghana, West Africa, has the potential to reduce the tendency of asthmatic episodes. In the present paper we studied the effect of regular ingestion of aqueous extract of UNCP on hematological and histopathological changes that occur in ovalbumin (OVA)-sensitized guinea pigs. OVA-sensitized guinea pigs were challenged with aerosolized OVA 1 hour after ingestion of 300 mg/kg (low dose) or 600 mg/kg (high dose) of UNCP for 35 consecutive days. Histopathological and haematological changes in the OVA-sensitized guinea pigs were evaluated. Both negative and positive controls with distilled water and prednisolone, respectively, were used. OVA-sensitized guinea pigs demonstrated concentration-independent reduction in immune response to aerosolized OVA. There were no histo-architectural changes in the bronchiolar smooth muscles of the treated groups. Unsweetened natural cocoa powder has potential anti-asthmatic properties when administered orally at the doses tested. PMID:25004832

  17. FOLH1/GCPII is elevated in IBD patients, and its inhibition ameliorates murine IBD abnormalities

    PubMed Central

    Wozniak, Krystyna M.; Stathis, Marigo; Hollinger, Kristen R.; Thomas, Ajit G.; Rojas, Camilo; Vornov, James J.; Marohn, Michael; Li, Xuhang; Slusher, Barbara S.

    2016-01-01

    Recent gene-profiling analyses showed significant upregulation of the folate hydrolase (FOLH1) gene in the affected intestinal mucosa of patients with inflammatory bowel disease (IBD). The FOLH1 gene encodes a type II transmembrane glycoprotein termed glutamate carboxypeptidase II (GCPII). To establish that the previously reported increased gene expression was functional, we quantified the glutamate carboxypeptidase enzymatic activity in 31 surgical specimens and report a robust 2.8- to 41-fold increase in enzymatic activity in the affected intestinal mucosa of IBD patients compared with an uninvolved area in the same patients or intestinal mucosa from healthy controls. Using a human-to-mouse approach, we next showed a similar enzymatic increase in two well-validated IBD murine models and evaluated the therapeutic effect of the potent FOLH1/ GCPII inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) (IC50 = 300 pM). In the dextran sodium sulfate (DSS) colitis model, 2-PMPA inhibited the GCPII activity in the colonic mucosa by over 90% and substantially reduced the disease activity. The significance of the target was confirmed in FOLH1−/− mice who exhibited resistance to DSS treatment. In the murine IL-10−/− model of spontaneous colitis, daily 2-PMPA treatment also significantly reduced both macroscopic and microscopic disease severity. These results provide the first evidence of FOLH1/GCPII enzymatic inhibition as a therapeutic option for IBD. PMID:27536732

  18. Altered patterns of cortical activation in ALS patients during attention and cognitive response inhibition tasks.

    PubMed

    Goldstein, L H; Newsom-Davis, I C; Bryant, V; Brammer, M; Leigh, P N; Simmons, A

    2011-12-01

    Since amyotrophic lateral sclerosis (ALS) can be accompanied by executive dysfunction, it is hypothesised that ALS patients will have impaired performance on tests of cognitive inhibition. We predicted that ALS patients would show patterns of abnormal activation in extramotor regions when performing tests requiring the inhibition of prepotent responses (the Stroop effect) and the inhibition of prior negatively primed responses (the negative priming effect) when compared to healthy controls. Functional magnetic resonance imaging was used to measure activation during a sparse sequence block design paradigm investigating the Stroop and negative priming effects in 14 ALS patients and 8 healthy age- and IQ-matched controls. Behavioural measures of performance were collected. Both groups' reaction times (RTs) reflected the Stroop effect during scanning. The ALS and control groups did not differ significantly for any of the behavioural measures but did show significant differences in cerebral activation during both tasks. The ALS group showed increased activation predominantly in the left middle temporal gyrus (BA 20/21), left superior temporal gyrus (BA 22) and left anterior cingulate gyrus (BA 32). Neither group's RT data showed clear evidence of a negative priming effect. However the ALS group showed decreased activation, relative to controls, particularly in the left cingulate gyrus (BA 23/24), left precentral gyrus (BA 4/6) and left medial frontal gyrus (BA 6). Greater cerebral activation in the ALS group accompanying the performance of the Stroop effect and areas of decreased activation during the negative priming comparison suggest altered inhibitory processing in ALS, consistent with other evidence of executive dysfunction in ALS. The current findings require further exploration in a larger study. PMID:21556876

  19. Prevalence of asthma–COPD overlap syndrome among primary care asthmatics with a smoking history: a cross-sectional study

    PubMed Central

    Kiljander, Toni; Helin, Timo; Venho, Kari; Jaakkola, Antero; Lehtimäki, Lauri

    2015-01-01

    Background: The overlap between asthma and chronic obstructive pulmonary disease (COPD) is an important clinical phenomenon. However, the prevalence of asthma–COPD overlap syndrome (ACOS) is not known. Aims: To investigate the prevalence of ACOS among asthmatic patients with a smoking history, and evaluate the factors predicting ACOS in this patient group. Methods: We investigated 190 primary care asthma patients with no previous diagnosis of COPD, but who were either current or ex-smokers, with a smoking history of at least 10 pack-years. Spirometry was performed on all the patients while they were taking their normal asthma medication. Patients were considered to have ACOS if their postbronchodilator forced expiratory volume in 1 s/forced vital capacity was <0.70. Results: Fifty-two (27.4%) of the patients were found to have ACOS. Age ⩾60 years and smoking for ⩾20 pack-years were the best predictors of ACOS. If both of these criteria were met, the odds ratio (95% confidence interval) for ACOS was 6.08 (2.11–17.49), compared with the situation where neither of these criteria were fulfilled. Conclusions: There is a high prevalence of ACOS among primary health care asthmatics with a positive smoking history but no previous diagnosis of COPD. In this population, age over 60 years and a smoking history of more than 20 pack-years were the best predictors of ACOS. PMID:26182124

  20. Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients: The EXACT-HF Study

    PubMed Central

    Givertz, Michael M.; Anstrom, Kevin J.; Redfield, Margaret M.; Deswal, Anita; Haddad, Haissam; Butler, Javed; Tang, W.H. Wilson; Dunlap, Mark E.; LeWinter, Martin M.; Mann, Douglas L.; Felker, G. Michael; O’Connor, Christopher M.; Goldsmith, Steven R.; Ofili, Elizabeth O.; Saltzberg, Mitchell T.; Margulies, Kenneth B.; Cappola, Thomas P.; Konstam, Marvin A.; Semigran, Marc J.; McNulty, Steven E.; Lee, Kerry L.; Shah, Monica R.; Hernandez, Adrian F.

    2015-01-01

    Background Oxidative stress may contribute to heart failure (HF) progression. Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes. Methods and Results We randomized 253 patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≤40%, and serum uric acid levels ≥9.5 mg/dL to receive allopurinol (target dose, 600 mg daily) or placebo in a double-blind, multicenter trial. The primary composite endpoint at 24 weeks was based on survival, worsening HF, and patient global assessment. Secondary endpoints included change in quality of life, submaximal exercise capacity, and LVEF. Uric acid levels were significantly reduced with allopurinol compared to placebo (treatment difference, −4.2 [−4.9, −3.5] mg/dL and −3.5 [−4.2, −2.7] mg/dL at 12 and 24 weeks, respectively, both P<0.0001). At 24 weeks, there was no significant difference in clinical status between the allopurinol- and placebo-treated patients (worsened 45% vs. 46%, unchanged 42% vs. 34%, improved 13% vs. 19%, respectively; P=0.68). At 12 and 24 weeks, there was no significant difference in change in Kansas City Cardiomyopathy Questionnaire scores or 6-minute walk distances between the 2 groups. At 24 weeks, LVEF did not change in either group or between groups. Rash occurred more frequently with allopurinol (10% vs. 2%, P=0.01), but there was no difference in serious adverse event rates between the groups (20% vs. 15%, P=0.36). Conclusions In high-risk HF patients with reduced ejection fraction and elevated uric acid levels, xanthine oxidase inhibition with allopurinol failed to improve clinical status, exercise capacity, quality of life, or LVEF at 24 weeks. PMID:25986447

  1. Working Memory and Response Inhibition in Patients With Bipolar I Disorder During Euthymic Period

    PubMed Central

    Farahmand, Zahra; Tehrani-Doost, Mehdi; Amini, Homayoun; Mohammadi, Abolfazl; Mirzaei, Mosleh; Mohamadzadeh, Azar

    2015-01-01

    Background: Several cognitive domains, including attention, memory, and executive functions are impaired in bipolar disorder. Objectives: This study aimed to investigate two executive functions (working memory and response inhibition) in patients with bipolar I disorder during remission of the symptoms. Patients and Methods: In this case-control design, 30 bipolar I patients (18 to 45 years old) were matched with 30 ones in the control group in terms of age, gender, and education. The patients were selected from Roozbeh Psychiatric Hospital (a hospital affiliated to Tehran University of Medical Sciences) from May to October 2013. They were evaluated and contrasted using working memory (Spatial Span and Spatial Working Memory (SSP and SWM)) and response inhibition (Stop Signal Task (SST)) tests. Results: We used independent t-tests for comparing and contrasting 2 groups on total and sub-scales scores of these 3 tests. In terms of SWM test there was a significant difference in between-group error between the two groups (P = 0.05); there was also a meaningful difference between the strategies used by two groups (P = 0.05). In SSP test, a significant difference appeared between averages of span length of the two groups. In the first and last item delays, there was also a clear difference, but the total error index was not noticeably different. In SST test, the direction error indicator in start-stop trials indicated a major difference, while in successful stops ratio, the case group had a lower ratio. In addition, reaction time to stop signs in bipolar group was meaningfully lower than the control group. Conclusion: In conclusion, even during remission phase, executive dysfunction is detectable at least in some areas in patients with bipolar disorder. PMID:26251656

  2. Sulfasalazine and its metabolites inhibit platelet function in patients with inflammatory arthritis.

    PubMed

    MacMullan, Paul A; Madigan, Anne M; Paul, Nevin; Peace, Aaron J; Alagha, Ahmed; Nolan, Kevin B; McCarthy, Geraldine M; Kenny, Dermot

    2016-02-01

    The purpose of this study is to assess the effect of sulfasalazine and its metabolites on platelet function in patients with inflammatory arthritis (IA). One hundred thirty-five consecutive patients with an established diagnosis of IA were screened. Those with a history of cardiovascular disease (CVD), taking anti-platelet agents or non-steroidal anti-inflammatory drugs (NSAIDs) were excluded. A total of 32 patients were investigated, 15 taking sulfasalazine and 17 taking other disease-modifying anti-rheumatic drugs (DMARDs) and no sulfasalazine. These two cohorts were compared to 15 patients with stable CVD on long-term aspirin. The effect of sulfasalazine and its metabolites on arachidonic acid (AA)-induced platelet aggregation was also tested in vitro in samples from healthy donors (n = 18). Demographics, CVD risk factors and disease activity indices were similar in the sulfasalazine and other DMARD groups. AA-induced platelet aggregation was significantly inhibited in the sulfasalazine group (9 ± 7 %) and comparable to that in the aspirin group (10 ± 6 %). In contrast, there was no effect on AA-induced platelet aggregation in the other DMARDs group (77 ± 12 %) (p < 0.001). Furthermore, sulfasalazine therapy had no effect on platelet aggregation in response to multiple other agonists. Sulfasalazine and its metabolites (5-aminosalicylic acid and sulfapyridine) exerted an additive and dose-dependent inhibitory effect on AA-induced platelet aggregation in vitro (p < 0.001). The inhibition of AA-induced platelet aggregation by sulfasalazine is comparable to that achieved by aspirin and is dependent on both sulfasalazine and its metabolites. This represents a potential mechanism that may contribute to the known cardioprotective effect of sulfasalazine in patients with IA. PMID:25253538

  3. Inhaled nedocromil sodium reduces histamine release from isolated large airway segments of asthmatic subjects in vivo.

    PubMed

    Maxwell, D L; Hawksworth, R J; Lee, T H

    1993-09-01

    Placement of an intrabronchial single balloon catheter provides the possibility of measuring histamine release in isolated large airway segments in vivo. We wanted to assess the protective effect of nedocromil sodium on intrabronchial histamine release after hyperosmolar challenge. Six mild asthmatics were bronchoscoped 30 min after inhalation of 4 mg nedocromil sodium or placebo, given via a metered dose inhaler in a randomized, double-blind, cross-over study. Lavage of the left main bronchus was carried out proximal to a balloon catheter inflated at its bifurcation, and specimens were assayed for histamine and prostaglandin D2 (PGD2) by radioimmunoassay. The rise in histamine concentration in bronchial epithelial fluid following hyperosmolar saline challenge was significantly greater following placebo than following nedocromil sodium (mean +/- SEM prechallenge histamine concentration on placebo day 6.9 +/- 2.9 nM; post-challenge: 25.3 +/- 8.0 nM; mean +/- SEM prechallenge histamine concentration on the day nedocromil sodium was given: 3.7 +/- 0.7 nM; post-challenge 5.8 +/- 1.7 nM). Changes in PGD2 levels reflected the changes in histamine, but the variability of response was large, and there were no significant differences between the effects of placebo and nedocromil sodium. The procedure caused significantly greater falls in peak expiratory flow rates following placebo (mean +/- SEM percentage fall 20.2 +/- 4.4%) than following nedocromil sodium (0.9 +/- 5.8%, p < 0.02). We conclude that there is tonic basal histamine release within asthmatic airways, and that nedocromil sodium inhibits histamine release from mediator cells in vivo. PMID:7693506

  4. Chaga mushroom extract inhibits oxidative DNA damage in lymphocytes of patients with inflammatory bowel disease.

    PubMed

    Najafzadeh, Mojgan; Reynolds, P Dominic; Baumgartner, Adolf; Jerwood, David; Anderson, Diana

    2007-01-01

    Inflammatory Bowel Disease (IBD) is partly caused by oxidative stress from free radicals and reduced antioxidant levels. Using hydrogen peroxide to induce oxidative stress in vitro in peripheral lymphocytes we investigated the induction of DNA damage supplemented with ethanolic extract of Chaga mushroom as a protective antioxidant. Lymphocytes were obtained from 20 IBD patients and 20 healthy volunteers. For treatment, a constant H_{2}O_{2 } dose (50 microg/ml) was used with variable doses of Chaga extract (10-500 microg/ml). DNA damage was evaluated in 50 cells per individual and dose using the Comet assay (making 1000 observations per experimental point ensuring appropriate statistical power). Chaga supplementation resulted in a 54.9% (p < 0.001) reduction of H_{2}O_{2 } induced DNA damage within the patient group and 34.9% (p < 0.001) within the control group. Lymphocytes from Crohn's disease (CD) patients had a greater basic DNA damage than Ulcerative Colitis (UC) patients (p < 0.001). Conclusively, Chaga extract reduces oxidative stress in lymphocytes from IBD patients and also healthy individuals when challenged in vitro. Thus, Chaga extract could be a possible and valuable supplement to inhibit oxidative stress in general. PMID:18997282

  5. Platelet inhibition with prasugrel in patients with acute myocardial infarction undergoing therapeutic hypothermia after cardiopulmonary resuscitation.

    PubMed

    Flierl, Ulrike; Röntgen, Philipp; Zauner, Florian; Tongers, Jörn; Berliner, Dominik; Bauersachs, Johann; Schäfer, Andreas

    2016-05-01

    Acute myocardial infarction (AMI) is the leading cause for out-of-hospital cardiac arrest. Therapeutic hypothermia improves neurological outcome in combination with early revascularisation, but seems to affect clopidogrel responsiveness. The more potent thienopyridine prasugrel has not yet been sufficiently evaluated during therapeutic hypothermia. We investigated 23 consecutive AMI patients (61 ± 11 years) following out-of-hospital resuscitation undergoing revascularisation and therapeutic hypothermia. Prasugrel efficacy was assessed by the platelet-reactivity-index (PRI) before and 2, 4, 6, 12, 24, 48, and 72 hours (h) following a loading dose of 60 mg via a gastric tube. Mean PRI (± SD) was 70 ± 12 % prior to loading and 60 ± 16 % (2 h, ns), 52 ± 21 % (4 h, p< 0.01), 42 ± 26 % (6 h, p< 0.01), 37 ± 21 % (12 h, p< 0.01), 27 ± 23 % (24 h, p< 0.01), 18 ± 14 % (48 h, p< 0.01), and 13 ± 10 % (72 h, p< 0.01) after loading. Sufficient platelet inhibition occurred later compared to stable AMI patients (6 h vs 2 h); however, high on-treatment platelet reactivity significantly decreased over time and was non-existent after 72 h (PRI> 50 %: 2 h: 72 %, 4 h: 52 %, 6 h: 43 %, 12 h: 29 %, 24 h: 17 %, 48 h: 5 %, 72 h: 0 %). There was no relation between 30-day mortality rate (26 %) and PRI values. Prasugrel significantly reduced platelet reactivity even during vasopressor use, analgosedation and therapeutic hypothermia. Despite a significant delay compared to stable AMI patients, sufficient platelet inhibition was reached in 83 % of patients within 24 h. Therefore, prasugrel administration via gastric tube might be a useful therapeutic strategy in these patients at high risk, providing potent and effective P2Y12 inhibition. PMID:26790884

  6. Spiruchostatin A Inhibits Proliferation and Differentiation of Fibroblasts from Patients with Pulmonary Fibrosis

    PubMed Central

    Davies, Elizabeth R.; Haitchi, Hans Michael; Thatcher, Thomas H.; Sime, Patricia J.; Kottmann, R. Matthew; Ganesan, Arasu; Packham, Graham; O'Reilly, Katherine M. A.

    2012-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disorder characterized by the proliferation of interstitial fibroblasts and the deposition of extracellular matrix causing impaired gas exchange. Spiruchostatin A (SpA) is a histone deacetylase inhibitor (HDI) with selectivity toward Class I enzymes, which distinguishes it from other nonspecific HDIs that are reported to inhibit (myo)fibroblast proliferation and differentiation. Because the selectivity of HDIs may be important clinically, we postulated that SpA inhibits the proliferation and differentiation of IPF fibroblasts. Primary fibroblasts were grown from lung biopsy explants obtained from patients with IPF or from normal control subjects, using two-dimensional or three-dimensional culture models. The effect of SpA on fibroproliferation in serum-containing medium ± transforming growth factor (TGF)–β1 was quantified by methylene blue binding. The acetylation of histone H3, the expression of the cell-cycle inhibitor p21waf1, and the myofibroblast markers α–smooth muscle actin (α-SMA) and collagens I and III were determined by Western blotting, quantitative RT-PCR, immunofluorescent staining, or colorimetry. SpA inhibited the proliferation of IPF or normal fibroblasts in a time-dependent and concentration-dependent manner (concentration required to achieve 50% inhibition = 3.8 ± 0.4 nM versus 7.8 ± 0.2 nM, respectively; P < 0.05), with little cytotoxicity. Western blot analyses revealed that SpA caused a concentration-dependent increase in histone H3 acetylation, paralleling its antiproliferative effect. SpA also increased p21waf1 expression, suggesting that direct cell-cycle regulation was the mechanism of inhibiting proliferation. Although treatment with TGF-β1 induced myofibroblast differentiation associated with increased expression of α-SMA, collagen I and collagen III and soluble collagen release, these responses were potently inhibited by SpA. These data support the concept that

  7. Quantitative Assessment of Global and Regional Air Trappings Using Non-Rigid Registration and Regional Specific Volume Change of Inspiratory/Expiratory CT Scans: Studies on Healthy Volunteers and Asthmatics

    PubMed Central

    Lee, Eunsol; Lee, Hyun Joo; Chae, Eun Jin; Lee, Sang Min; Oh, Sang Young; Kim, Namkug

    2015-01-01

    Objective The purpose of this study was to compare air trapping in healthy volunteers with asthmatics using pulmonary function test and quantitative data, such as specific volume change from paired inspiratory CT and registered expiratory CT. Materials and Methods Sixteen healthy volunteers and 9 asthmatics underwent paired inspiratory/expiratory CT. ΔSV, which represents the ratio of air fraction released after exhalation, was measured with paired inspiratory and anatomically registered expiratory CT scans. Air trapping indexes, ΔSV0.4 and ΔSV0.5, were defined as volume fraction of lung below 0.4 and 0.5 ΔSV, respectively. To assess the gravity effect of air-trapping, ΔSV values of anterior and posterior lung at three different levels were measured and ΔSV ratio of anterior lung to posterior lung was calculated. Color-coded ΔSV map of the whole lung was generated and visually assessed. Mean ΔSV, ΔSV0.4, and ΔSV0.5 were compared between healthy volunteers and asthmatics. In asthmatics, correlation between air trapping indexes and clinical parameters were assessed. Results Mean ΔSV, ΔSV0.4, and ΔSV0.5 in asthmatics were significantly higher than those in healthy volunteer group (all p < 0.05). ΔSV values in posterior lung in asthmatics were significantly higher than those in healthy volunteer group (p = 0.049). In asthmatics, air trapping indexes, such as ΔSV0.5 and ΔSV0.4, showed negative strong correlation with FEF25-75, FEV1, and FEV1/FVC. ΔSV map of asthmatics showed abnormal geographic pattern in 5 patients (55.6%) and disappearance of anterior-posterior gradient in 3 patients (33.3%). Conclusion Quantitative assessment of ΔSV (the ratio of air fraction released after exhalation) shows the difference in extent of air trapping between health volunteers and asthmatics. PMID:25995694

  8. The impact of vitamin D on asthmatic human airway smooth muscle.

    PubMed

    Hall, Sannette C; Fischer, Kimberly D; Agrawal, Devendra K

    2016-02-01

    Asthma is a chronic heterogeneous disorder, which involves airway inflammation, airway hyperresponsiveness (AHR) and airway remodeling. The airway smooth muscle (ASM) bundle regulates the broncho-motor tone and plays a critical role in AHR as well as orchestrating inflammation. Vitamin D deficiency has been linked to increased severity and exacerbations of symptoms in asthmatic patients. It has been shown to modulate both immune and structural cells, including ASM cells, in inflammatory diseases. Given that current asthma therapies have not been successful in reversing airway remodeling, vitamin D supplementation as a potential therapeutic option has gained a great deal of attention. Here, we highlight the potential immunomodulatory properties of vitamin D in regulating ASM function and airway inflammation in bronchial asthma. PMID:26634624

  9. MiR-940 inhibits hepatocellular carcinoma growth and correlates with prognosis of hepatocellular carcinoma patients.

    PubMed

    Yuan, Bo; Liang, Yasha; Wang, Duoning; Luo, Fengming

    2015-07-01

    Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related death in China. Deregulation of microRNA (miRNA) contributes to HCC development by influencing cell growth, apoptosis, migration or invasion. It has been proved that miR-940 plays important roles in various cancers. Here we investigated the role of miR-940 in HCC. We found that miR-940 was remarkably decreased in HCC tissues and cell lines. Importantly, lower miR-940 expression in HCC tissues significantly correlated with the reduced patient's survival rate. Overexpression of miR-940 inhibited HCC cell line growth and induced cell apoptosis, and vice versa. Estrogen-related receptor gamma (ESRRG) was targeted by miR-940, and suppression of ESRRG inhibited HCC cell lines growth and induced cell apoptosis. In conclusion, we found that a lower level of miR-940 in HCC promoted cellular proliferation via ESRRG, which may lead to the short survival period of HCC patients. PMID:25940592

  10. Special considerations for adolescent athletic and asthmatic patients.

    PubMed

    Wuestenfeld, Jan C; Wolfarth, Bernd

    2013-01-01

    Asthma is defined as a chronic inflammatory disorder of the airways with bronchial hyperresponsiveness and variable bronchoconstriction, and is one of the most common diseases in childhood and adolescence. Exercise-induced asthma-like symptoms and asthma are also frequently seen in highly trained athletes. Exercise-induced asthma (EIA) and exercise-induced bronchoconstriction (EIB) are found in 8%-10% of healthy school-aged children and in 35% of children with asthma. Highly increased ventilation, inhalation of cold, dry air and air pollutants (eg, chlorine) are thought to be important triggers for EIA and EIB. EIA is often experienced concurrently with vocal cord dysfunction, which needs to be considered during the differential diagnosis. The pharmacological treatment of EIA is similar to the treatment of asthma in nonexercising adolescents. The therapy is based on anti-inflammatory drugs (eg, inhaled glucocorticosteroids) and bronchodilators (eg, β2-agonists). The treatment of EIB is comparable to the treatment of EIA and leukotriene modifiers offer a new and promising treatment option, particularly in EIB. Generally, athletes may not use β2-agonists according to the prohibited list of the World Anti-Doping Agency (WADA). However, the WADA list contains specific β2-agonistic substances that are permitted to be used by inhalation. PMID:24379703

  11. Special considerations for adolescent athletic and asthmatic patients

    PubMed Central

    Wuestenfeld, Jan C; Wolfarth, Bernd

    2013-01-01

    Asthma is defined as a chronic inflammatory disorder of the airways with bronchial hyperresponsiveness and variable bronchoconstriction, and is one of the most common diseases in childhood and adolescence. Exercise-induced asthma-like symptoms and asthma are also frequently seen in highly trained athletes. Exercise-induced asthma (EIA) and exercise-induced bronchoconstriction (EIB) are found in 8%–10% of healthy school-aged children and in 35% of children with asthma. Highly increased ventilation, inhalation of cold, dry air and air pollutants (eg, chlorine) are thought to be important triggers for EIA and EIB. EIA is often experienced concurrently with vocal cord dysfunction, which needs to be considered during the differential diagnosis. The pharmacological treatment of EIA is similar to the treatment of asthma in nonexercising adolescents. The therapy is based on anti-inflammatory drugs (eg, inhaled glucocorticosteroids) and bronchodilators (eg, β2-agonists). The treatment of EIB is comparable to the treatment of EIA and leukotriene modifiers offer a new and promising treatment option, particularly in EIB. Generally, athletes may not use β2-agonists according to the prohibited list of the World Anti-Doping Agency (WADA). However, the WADA list contains specific β2-agonistic substances that are permitted to be used by inhalation. PMID:24379703

  12. Osteoporosis in the at-risk asthmatic.

    PubMed

    Aljubran, S A; Whelan, G J; Glaum, M C; Lockey, R F

    2014-11-01

    The effect of inhaled glucocorticosteroids (ICS) on bone metabolism and subsequent osteoporosis is controversial. Explanations for this controversy include various study designs, duration of use, outcome measures, and population demographics of research studies with intranasal or inhalational ICS. Patients with poorly controlled asthma are at greatest risk of osteoporosis because they are commonly treated with intermittent or continuous systemic corticosteroids (SCS) or high-dose ICS. A 45-year-old Caucasian woman presents with moderate-to-severe asthma with frequent albuterol use and nighttime awakenings at least once weekly. She is on fluticasone/salmeterol 500/50 μg one inhalation twice daily and montelukast 10 mg/day. She requires prednisone 15 mg three times per day for 5 days up to three times a year. Is this patient at greater risk of osteopenia, characterized by a T-score between -1.0 and -2.5, and subsequent osteoporosis and an increased risk of fractures? If she has osteopenia, should she be treated with a bisphosphonate? The risk of osteoporosis and fracture increases significantly with frequent administration of SCS, and patients on such medications should undergo preventative measures and treatment. This study discuses factors that contribute to an increased risk of osteoporosis/osteopenia in patients with asthma and suggests recommendations based on the current literature. PMID:25039444

  13. Development of asthmatic inflammation in mice following early-life exposure to ambient environmental particulates and chronic allergen challenge

    PubMed Central

    Herbert, Cristan; Siegle, Jessica S.; Shadie, Alexander M.; Nikolaysen, Stina; Garthwaite, Linda; Hansbro, Nicole G.; Foster, Paul S.; Kumar, Rakesh K.

    2013-01-01

    SUMMARY Childhood exposure to environmental particulates increases the risk of development of asthma. The underlying mechanisms might include oxidant injury to airway epithelial cells (AEC). We investigated the ability of ambient environmental particulates to contribute to sensitization via the airways, and thus to the pathogenesis of childhood asthma. To do so, we devised a novel model in which weanling BALB/c mice were exposed to both ambient particulate pollutants and ovalbumin for sensitization via the respiratory tract, followed by chronic inhalational challenge with a low mass concentration of the antigen. We also examined whether these particulates caused oxidant injury and activation of AEC in vitro. Furthermore, we assessed the potential benefit of minimizing oxidative stress to AEC through the period of sensitization and challenge by dietary intervention. We found that characteristic features of asthmatic inflammation developed only in animals that received particulates at the same time as respiratory sensitization, and were then chronically challenged with allergen. However, these animals did not develop airway hyper-responsiveness. Ambient particulates induced epithelial injury in vitro, with evidence of oxidative stress and production of both pro-inflammatory cytokines and Th2-promoting cytokines such as IL-33. Treatment of AEC with an antioxidant in vitro inhibited the pro-inflammatory cytokine response to these particulates. Ambient particulates also induced pro-inflammatory cytokine expression following administration to weanling mice. However, early-life dietary supplementation with antioxidants did not prevent the development of an asthmatic inflammatory response in animals that were exposed to particulates, sensitized and challenged. We conclude that injury to airway epithelium by ambient environmental particulates in early life is capable of promoting the development of an asthmatic inflammatory response in sensitized and antigen-challenged mice

  14. Effects of nebulized terbutaline on oxygen saturation in acute asthmatic children.

    PubMed

    Lin, Y Z; Hsieh, K H; Shih, T Y; Chen, W; Wu, K W

    1994-01-01

    To evaluate the paradoxical effect of oxygen desaturation following beta-2 bronchodilator nebulization treatment in acute asthmatic children, a total of 47 patients, aged between 1.8 and 14 years, 27 males and 20 females, were studied. Twenty ml of nebulized normal saline (NS), followed by 10 mg (4 ml) of terbutaline sulphate solution (TSS) in 20 ml NS, were delivered by an ultrasonic nebulizer in 10 min to each patient through a connecting air tube placed in front of the nose and mouth. Oxygen saturation (SaO2) and pulse rate were monitored, using a pulse oximeter, before study and every two minutes until the end of the study. The clinical severity score and peak expiratory flow rate (PEFR) were checked before the study, at the end of inhalation of NS, and at the end of inhalation of TSS. SaO2 was increased both after nebulized NS and TSS when compared with the pre-study data (p < 0.05 and p < 0.0001, respectively). Twenty two cases (47%) during NS and 12 cases (25%) during TSS nebulization had SaO2 below the pre-study level. The mean decrease of SaO2 for the former was 1.62 +/- 0.95% (range: 1.00% to 4.26%), and 1.64 +/- 0.83% (range: 1.02% to 3.13%) for the latter (p > 0.9). No SaO2 decrease after nebulized TSS was observed in any of the seven severe asthmatic children with a prestudy SaO2 < or = 90%. The clinical severity score and PEFR were also significantly improved both after nebulized NS and TSS (p < 0.0001 and p < 0.001, respectively for NS, and both p < 0.0001 for TSS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7942023

  15. Executive function in chronic pain patients and healthy controls: Different cortical activation during response inhibition in fibromyalgia

    PubMed Central

    Glass, J.; Williams, DA; Fernandez-Sanchez, M.; Kairys, A; Barjola, P.; Heitzeg, M.; Clauw, DJ; Schmidt-Wilcke, T.

    2013-01-01

    The primary symptom of fibromyalgia (FM) is chronic, widespread pain; however, patients report additional symptoms including decreased concentration and memory. Performance based deficits are seen mainly in tests of working memory and executive function. Neural correlates of executive function were investigated in 18 FM patients and 14 age-matched HCs during a simple go/no-go task (response inhibition) while they underwent functional magnetic resonance imaging (fMRI). Performance was not different between FM and HC, in either reaction time or accuracy. However, fMRI revealed that FM patients had lower activation in the right pre-motor cortex, supplementary motor area (SMA), mid cingulate cortex (MCC), putamen and, after controlling for anxiety, in the right insular cortex (IC) and right inferior frontal gyrus (IFG). A hyper-activation in FM patients was seen in the right inferior temporal gyrus/fusiform gyrus. Despite the same RTs and accuracy, FM patients show less brain activation in cortical structures in the inhibition network (specifically in areas involved in response selection/motor preparation) and the attention network along with increased activation in brain areas not normally part of the inhibition network. We hypothesize that response -inhibition and pain perception may rely on partially overlapping networks, and that in chronic pain patients resources taken up by pain processing may not be available for executive functioning tasks such as response inhibition. Compensatory cortical plasticity may be required to achieve performance on par with control groups. PMID:21945593

  16. Addition of Everolimus Post VEGFR Inhibition Treatment Failure in Advanced Sarcoma Patients Who Previously Benefited from VEGFR Inhibition: A Case Series

    PubMed Central

    Hays, John L.; Chen, James L.

    2016-01-01

    Background Patients with metastatic sarcoma who progress on vascular endothelial growth factor receptor inhibitors (VEGFRi) have limited treatment options. Upregulation of the mTOR pathway has been demonstrated to be a means of resistance to targeted VEGFRi in metastatic sarcoma. Patients and methods Retrospective cohort study to evaluate the clinical benefit at four months of combining mTOR inhibition (mTORi) via everolimus with VEGFRi in patients who have derived benefit from single-agent VEGFRi but have progressed. Patients with recurrent, metastatic soft tissue or bone sarcomas who progressed after deriving clinical benefit to VEGFRi beyond 12 weeks were continued on VEGFRi with the addition of everolimus (5 mg daily). Progression free survival was measured from start of VEGFRi to disease progression on single agent VEGFRi as well as from the addition of everolimus therapy to disease progression or drug discontinuation due to toxicity. Clinical benefit was defined as stable disease or partial response at 4 months. Results Nine patients were evaluated. Two patients did not tolerate therapy due to GI toxicity and one elected to discontinue therapy. Of the remaining six patients, the clinical benefit rate at four months was 50%. Progression free survival (PFS) for these patients was 3.1 months ranging from 0.5 to 7.2 months with one patient remaining on combination therapy. Conclusion In this heavily pre-treated, advanced sarcoma population, the addition of mTOR inhibition to VEGFRi based therapy resulted in a clinical benefit for a subset of patients. Prospective studies will be needed to verify these results. PMID:27295141

  17. A new multiple dose powder inhaler, (Turbuhaler), compared with a pressurized inhaler in a study of terbutaline in asthmatics.

    PubMed

    Persson, G; Gruvstad, E; Ståhl, E

    1988-08-01

    Twelve adult asthmatic patients participated in an open, randomized, cross-over comparison between cumulatively increasing doses of terbutaline sulphate administered via the multiple dose powder inhaler (Turbuhaler) or via a pressurized inhaler. Turbuhaler and the pressurized inhaler showed equipotency both with respect to bronchodilatation and side effects. Both treatments produced a significant increase in pulmonary function measurements, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). No increase in pulse rate was seen with either treatment but there was an increase in tremor at higher doses with both treatments. Inhalation of beta-agonists via Turbuhaler seems to be an effective way of treating asthma. PMID:3234516

  18. Reduced inhibition of Candida albicans adhesion by saliva from patients receiving oral cancer therapy.

    PubMed Central

    Umazume, M; Ueta, E; Osaki, T

    1995-01-01

    The effect of saliva on the adhesion of Candida albicans to epithelial cells was examined in vitro by using saliva from healthy controls and patients with oral squamous cell carcinoma. The adhesion of C. albicans to established epithelial tumor cells was reduced by 40% by salivary treatment of the C. albicans or epithelial cells. The inhibitory activity of saliva was almost completely abolished by anti-secretory immunoglobulin A antibody, concanavalin A, and mannose. Compared with saliva from healthy individuals, that from patients who had received chemoradiotherapy for oral carcinoma showed reduced suppression of C. albicans adhesion, which accompanied decreased salivary secretory immunoglobulin A and lactoferrin concentrations. A greater number of C. albicans cells adhered to buccal cells obtained from patients who had received chemoradiotherapy than to those from healthy individuals. Treatment of either epithelial cells or C. albicans with anticancer drugs induced an increase in adherence of epithelial cells and yeast cells. In contrast, concanavalin A- and mannose-pretreated C. albicans exhibited reduced adhesion to epithelial cells. No further decrease of C. albicans adhesion was observed when both epithelial cells and yeast phase C. albicans were treated with mannose. In conclusion, the inhibition of C. albicans adhesion by saliva depends largely on mannose residues on salivary glycoproteins and mannose is one of the binding ligands on both C. albicans and epithelial cells. In addition, anticancer therapy may induce oral C. albicans overgrowth by decreasing salivation and the concentrations of glycoproteins in saliva inhibiting C. albicans adhesion and by increasing the adhesive properties of both C. albicans and oral epithelial cells. PMID:7714204

  19. Supporting and Inhibiting Factors When Coping with Endometriosis From the Patientsʼ Perspective

    PubMed Central

    Kundu, S.; Wildgrube, J.; Schippert, C.; Hillemanns, P.; Brandes, I.

    2015-01-01

    Aim: Endometriosis is a chronic gynaecological disorder with manifold symptoms and psychosocial effects on the lives of affected women. The prevalence of endometriosis is estimated to be up to ten percent of women of reproductive age. As a result of its unclear aetiology, only limited treatment options are available. The treatment and care of affected women is therefore a challenge for their doctors. There is a need for healthcare services to provide affected women with support to cope with the disorder better. The aim of the study was to identify supporting and inhibiting factors on disease management to develop new support ideas. Materials and Methods: The results are based on a content analysis evaluation of text responses from 135 women with confirmed endometriosis. Open questions about disease management were posed in a patient questionnaire. A classification system was developed according to Mayrings Qualitative Content Analysis, which allowed the main topics to be identified and summarised qualitatively using a quantitative intermediate step. Results: Social support, treatment, as well as professional and healthcare system performance were found to be particularly supportive by patients. However, when questioned about inhibiting factors, healthcare system professionals and their performance were most commonly criticised. Just over 50 % of women expressed their criticism of doctors. Quality of care and empathy towards the patients were especially criticised. There is also a need for improvement with regard to communication and general support from doctors. The results illustrate the importance of doctors for women affected by endometriosis, but make it clear that there is a great need for improvement with regard to the profession. Conclusion: The results provide the first indication of problem areas in the management of endometriosis from which approaches could be developed to improve care. However, it must be pointed out that the perspective of affected

  20. EFFECTS OF 0.1 PPM NITROGEN DIOXIDE ON AIRWAYS OF NORMAL AND ASTHMATIC SUBJECTS

    EPA Science Inventory

    It has been reported that inhalation of nitrogen dioxide (NO2) will enhance the bronchial reactivity of asthmatics. This study was designed to evaluate the respiratory effect of a 1-h exposure of normal subjects and of atopic asthmatics to 0.1 parts per million (ppm) NO2. Fifteen...

  1. Volumes and Breathing Patterns during Speech in Healthy and Asthmatic Subjects.

    ERIC Educational Resources Information Center

    Loudon, Robert G.; And Others

    1988-01-01

    Lung volumes and ventilatory patterns used by 10 healthy and 14 asthmatic subjects during conversation, monologue, and counting at two loudness levels were studied. Asthmatics were found to favor respiratory over communications needs. They used a greater percentage of their reduced vital capacity, with slower inspiratory and faster expiratory flow…

  2. Ozone-induced changes in pulmonary function and bronchial responsiveness in asthmatics

    SciTech Connect

    Kreit, J.W.; Gross, K.B.; Moore, T.B.; Lorenzen, T.J.; D'Arcy, J.; Eschenbacher, W.L.

    1989-01-01

    To compare the responses of asthmatic and normal subjects to high effective doses of ozone, nine asthmatic and nine normal subjects underwent two randomly assigned 2-h exposures to filtered, purified air and 0.4 ppm ozone with alternating 15-min periods of rest and exercise on a cycle ergometer (minute ventilation = 30 l.min-1.m-2). Before and after each exposure, pulmonary function and bronchial responsiveness to methacholine were measured and symptoms were recorded. Ozone exposure was associated with a statistically significant decrease in forced vital capacity (FVC), forced expired volume in 1 s (FEV1), percent FEV1 (FEV1%), and forced expired flow at 25-75% FVC (FEF25-75) in both normal and asthmatic subjects. However, comparing the response of asthmatic and normal subjects to ozone revealed a significantly greater percent decrease in FEV1, FEV1%, and FEF25-75 in the asthmatic subjects. The effect of ozone on FVC and symptom scores did not differ between the two groups. In both normal and asthmatic subjects, exposure to ozone was accompanied by a significant increase in bronchial responsiveness. We conclude that exposure to a high effective ozone dose produces 1) increased bronchial responsiveness in both normal and asthmatic subjects, 2) greater airways obstruction in asthmatic than in normal subjects, and 3) similar symptoms and changes in lung volumes in the two groups.

  3. Levels of Aspiration of Parents for Their Asthmatic, Diabetic, and Healthy Children.

    ERIC Educational Resources Information Center

    Hilliard, Jomary P.; And Others

    1985-01-01

    Employed a modified Rotter Level of Aspiration (LOA) task to assess parents' goal setting for their asthmatic, diabetic, and healthy children (N=64). Results indicated mothers of asthmatic children showed no significant goal-setting differences from comparison mothers and were less controlling. Fathers were more rigid and less accommodating and…

  4. Self Image, Coping and Familial Interaction Among Asthmatic Children and Adolescents in Israel.

    ERIC Educational Resources Information Center

    Brook, U.; Tepper, I.

    1997-01-01

    Self-esteem, modes of coping, and interfamilial relationships of asthmatic children and adolescents were investigated (N=51; mean age=12.26). Asthmatic children have lower scores on psychological factors, coping with stress, and family interaction measures. Medical and psychological findings are related, and psychological and educational support…

  5. Florida Red Tide Toxins (Brevetoxins) and Longitudinal Respiratory Effects in Asthmatics.

    PubMed

    Bean, Judy A; Fleming, Lora E; Kirkpatrick, Barbara; Backer, Lorraine C; Nierenberg, Kate; Reich, Andrew; Cheng, Yung Sung; Wanner, Adam; Benson, Janet; Naar, Jerome; Pierce, Richard; Abraham, William M; Kirkpatrick, Gary; Hollenbeck, Julie; Zaias, Julia; Mendes, Eliana; Baden, Daniel G

    2011-09-01

    Having demonstrated significant and persistent adverse changes in pulmonary function for asthmatics after 1 hour exposure to brevetoxins in Florida red tide (Karenia brevis bloom) aerosols, we assessed the possible longer term health effects in asthmatics from intermittent environmental exposure to brevetoxins over 7 years. 125 asthmatic subjects were assessed for their pulmonary function and reported symptoms before and after 1 hour of environmental exposure to Florida red tide aerosols for upto 11 studies over seven years. As a group, the asthmatics came to the studies with normal standardized percent predicted pulmonary function values. The 38 asthmatics who participated in only one exposure study were more reactive compared to the 36 asthmatics who participated in ≥4 exposure studies. The 36 asthmatics participating in ≥4 exposure studies demonstrated no significant change in their standardized percent predicted pre-exposure pulmonary function over the 7 years of the study. These results indicate that stable asthmatics living in areas with intermittent Florida red tides do not exhibit chronic respiratory effects from intermittent environmental exposure to aerosolized brevetoxins over a 7 year period. PMID:22053149

  6. Association of School Social Networks' Influence and Mass Media Factors with Cigarette Smoking among Asthmatic Students

    ERIC Educational Resources Information Center

    Kanamori, Mariano; Beck, Kenneth H.; Carter-Pokras, Olivia

    2015-01-01

    Background: Around 10% of adolescent students under 18 years have current asthma. Asthmatic adolescents smoke as much or more than non-asthmatic adolescents. We explored the association between exposure to mass media and social networks' influence with asthmatic student smoking, and variations of these exposures by sex. Methods: This study…

  7. Attenuated response to repeated daily ozone exposures in asthmatic subjects

    SciTech Connect

    Gong, H. Jr.; Linn, W.S.; McManus, M.S.

    1997-01-01

    The development of attenuated response ({open_quotes}tolerance{close_quotes}) to daily ozone (O{sub 3}) exposures in the laboratory is well established in healthy adult volunteers. However, the capability of asthmatics to develop tolerance during multiday ozone exposures in unclear. We exposed 10 adult volunteers with mild asthma to 0.4 ppm O{sub 3} in filtered air for 3 h/d on 5 consecutive d. Two similar filtered-air exposures during the preceding week served as controls. Follow-up O{sub 3} exposures were performed 4 and 7 d after the most recent consecutive exposure. All exposures were performed in an environmental chamber at 31 {degrees}C and 35% relative humidity. The subjects performed moderate exercise (mean ventilation rate of 32 l/min) for 15 min of each half-hour. Responses were measured with spirometry and symptom evaluations before and after each exposure, and a bronchial reactivity test (methacholine challenge) was conducted after each exposure. All response measurements showed clinically and statistically significant day-to-day variation. Symptom and forced-expiratory-volume-in-1-s responses were similarly large on the 1st and 2nd O{sub 3} exposure days, after which they diminished progressively, approaching filtered air response levels by the 5th consecutive O{sub 3} day. This tolerance was partially lost 4 and 7 d later. Bronchial reactivity peaked after the first O{sub 3} exposure and remained somewhat elevated after all subsequent O{sub 3} exposures, relative to its control level following filtered-air exposures. Individual responses varied widely; more severe initial responses to O{sub 3} predicted less rapid attenuation. We concluded that asthmatics can develop tolerance to frequent high-level O{sub 3} exposures in much the same manner as normal subjects, although the process may be slower and less fully effective in asthmatics. 27 refs., 3 figs., 4 tabs.

  8. Assessment of food chemical intolerance in adult asthmatic subjects.

    PubMed Central

    Hodge, L.; Yan, K. Y.; Loblay, R. L.

    1996-01-01

    BACKGROUND: Identification of food chemical intolerance in asthmatic subjects can be reliably assessed by changes in the forced expiratory volume in one second (FEV1) in response to double blind, placebo controlled challenges on a strict elimination diet. However, this method is cumbersome and time consuming. A study was undertaken to determine whether changes in bronchial responsiveness to histamine following food chemical challenge without an elimination diet might be a faster, more convenient method. METHODS: Eleven adult asthmatic subjects were challenged twice with metabisulphite, aspirin, monosodium glutamate, artificial food colours, sodium nitrite/ nitrate, 0.5% citric acid solution (placebo), and sucrose (placebo) on separate days. During the first set of challenges subjects consumed a normal diet. Bronchial responsiveness to histamine was assessed 90 minutes after each challenge. A greater than twofold increase in bronchial responsiveness was considered positive. For one month prior to and during the second set of challenges subjects followed a strict elimination diet and FEV1 was monitored during and for two hours after each challenge. A fall in FEV1 of 20% or more was considered positive. RESULTS: Of the 77 food chemical challenges performed on an unmodified diet, 20 were positive (six placebo responses). In two subjects it was not possible to perform a histamine test after one of the chemical challenges because of poor spirometric function. Of the 77 food chemical challenges performed on an elimination diet, 11 were positive (no placebo responses). Excluding the two challenges in which there were no corresponding histamine tests, only on two occasions did the positive responses in both methods coincide, giving the unmodified diet method a sensitivity of 22%. CONCLUSIONS: Strict dietary elimination and measurement of FEV1 after double blind food chemical challenge remains the most reliable method for the detection of food chemical intolerance in

  9. Pentoxifylline Inhibits WNT Signalling in β-Cateninhigh Patient-Derived Melanoma Cell Populations

    PubMed Central

    Talar, Beata; Gajos-Michniewicz, Anna; Talar, Marcin; Chouaib, Salem; Czyz, Malgorzata

    2016-01-01

    Background The heterogeneity of melanoma needs to be addressed and combination therapies seem to be necessary to overcome intrinsic and acquired resistance to newly developed immunotherapies and targeted therapies. Although the role of WNT/β-catenin pathway in melanoma was early demonstrated, its contribution to the lack of the melanoma patient response to treatment was only recently recognized. Using patient-derived melanoma cell populations, we investigated the influence of pentoxifylline on melanoma cells with either high or low expression of β-catenin. Findings Our results indicate that pentoxifylline inhibits the activity of the canonical WNT pathway in melanoma cell populations with high basal activity of this signalling. This is supported by lowered overall activity of transcription factors TCF/LEF and reduced nuclear localisation of active β-catenin. Moreover, treatment of β-cateninhigh melanoma cell populations with pentoxifylline induces downregulation of genes that are targets of the WNT/β-catenin pathway including connective tissue growth factor (CTGF) and microphthalmia-associated transcription factor (MITF-M), a melanocyte- and melanoma cell-specific regulator. Conclusions These results suggest that pentoxifylline, a drug approved by the FDA in the treatment of peripheral arterial disease, might be tested in a subset of melanoma patients with elevated activity of β-catenin. This pharmaceutical might be tested as an adjuvant drug in combination therapies when the response to immunotherapy is prevented by high activity of the WNT/β-catenin pathway. PMID:27351373

  10. MiR-940 inhibits hepatocellular carcinoma growth and correlates with prognosis of hepatocellular carcinoma patients

    PubMed Central

    Yuan, Bo; Liang, Yasha; Wang, Duoning; Luo, Fengming

    2015-01-01

    Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related death in China. Deregulation of microRNA (miRNA) contributes to HCC development by influencing cell growth, apoptosis, migration or invasion. It has been proved that miR-940 plays important roles in various cancers. Here we investigated the role of miR-940 in HCC. We found that miR-940 was remarkably decreased in HCC tissues and cell lines. Importantly, lower miR-940 expression in HCC tissues significantly correlated with the reduced patient’s survival rate. Overexpression of miR-940 inhibited HCC cell line growth and induced cell apoptosis, and vice versa. Estrogen-related receptor gamma (ESRRG) was targeted by miR-940, and suppression of ESRRG inhibited HCC cell lines growth and induced cell apoptosis. In conclusion, we found that a lower level of miR-940 in HCC promoted cellular proliferation via ESRRG, which may lead to the short survival period of HCC patients. PMID:25940592

  11. Parameters of lung inflammation in asthmatic as compared to healthy children in a contaminated city

    PubMed Central

    2014-01-01

    Background The impact of air pollution on the respiratory system has been estimated on the basis of respiratory symptoms and lung function. However; few studies have compared lung inflammation in healthy and asthmatics children exposed to high levels of air pollution. The aim of the study was to elucidate the modulatory effect of air pollution on Cysteinyl-leukotrienes (Cys-LTs) levels in exhaled breath condensate (EBC) among healthy and asthmatic children. Methods We performed a cross-sectional comparative study. Children between 7–12 years of age, asthmatics and non-asthmatics, residents of a city with high levels of PM10 were included. In all cases, forced spirometry, Cys-LTs levels in EBC, and the International Study of Asthma and Allergies in Childhood questionnaire were evaluated. We also obtained average of PM10, CO, SO2 and O3 levels during the period of the study by the State Institute of Ecology. Results We studied 103 children (51 asthmatics and 52 non-asthmatics). Cys-LTs levels were higher in asthmatics than in non-asthmatics (77.3 ± 21.6 versus 60.3 ± 26.8 pg/ml; p = 0.0005). Also, Cys-LTs levels in children with intermittent asthma were lower than in children with persistent asthma (60.4 ± 20.4 versus 84.7 ± 19.2 pg/ml; p = 0.0001). In the multiple regression model, factors associated with levels of Cys-LTs were passive smoking (β = 13.1, p 0.04) and to be asthmatic (β = 11.5, p 0.03). Conclusions Cys-LTs levels are higher in asthmatic children than in healthy children in a contaminated city and its levels are also associated with passive smoking. PMID:25000942

  12. Is Health-Related Quality of Life Associated with Upper and Lower Airway Inflammation in Asthmatics?

    PubMed Central

    Scichilone, Nicola; Taormina, Salvatore; Pozzecco, Elena; Paternò, Alessandra; Baiardini, Ilaria; Canonica, Giorgio Walter; Bellia, Vincenzo

    2013-01-01

    Background. Allergic diseases impair health-related quality of life (HR-QoL). However, the relationship between airway inflammation and HR-QoL in patients with asthma and rhinitis has not been fully investigated. We explored whether the inflammation of upper and lower airways is associated with HR-QoL. Methods. Twenty-two mild allergic asthmatics with concomitant rhinitis (10 males, 38 ± 17 years) were recruited. The Rhinasthma was used to identify HR-QoL, and the Asthma Control Test (ACT) was used to assess asthma control. Subjects underwent lung function and exhaled nitric oxide (eNO) test, collection of exhaled breath condensate (EBC), and nasal wash. Results. The Rhinasthma Global Summary score (GS) was 25 ± 11. No relationships were found between GS and markers of nasal allergic inflammation (% eosinophils: r = 0.34, P = 0.24; ECP: r = 0.06, P = 0.87) or bronchial inflammation (pH of the EBC: r = 0.12, P = 0.44; bronchial NO: r = 0.27, P = 0.22; alveolar NO: r = 0.38, P = 0.10). The mean ACT score was 18. When subjects were divided into controlled (ACT ≥ 20) and uncontrolled (ACT < 20), the alveolar NO significantly correlated with GS in uncontrolled asthmatics (r = 0.60, P = 0.04). Conclusions. Upper and lower airways inflammation appears unrelated to HR-QoL associated with respiratory symptoms. These preliminary findings suggest that, in uncontrolled asthma, peripheral airway inflammation could be responsible for impaired HR-QoL. PMID:24073408

  13. [Controlled study of the effect of sports training on cardiopulmonary functions in asthmatic children and adolescents].

    PubMed

    Rothe, T; Köhl, C; Mansfeld, H J

    1990-09-01

    The influence of physical training on the cardiopulmonary system and on lung function of asthmatic children was determined in a controlled study. The children were all indoor patients of the Hochgebirgsklinik Davos, Switzerland. 36 children at the age of 10 to 16 years entered the study. They were placed into either a "free running group", a "swimming group" or a "control group." The children of the training groups underwent a training of at least 10 units of 30 minutes each in 3 weeks. The control group did not participate in any regular physical training. Heart rate was measured before and after a bicycle ergometer exercise of 5 minutes at 2.5 watts/kg body weight. This was repeated at the end of the study. In the "free running group" a significant decrease of the heart rate at rest (p less than 0.05) and at the end of bicycle ergometer exercise (p less than 0.01) could be seen. In the "swimming group" the decrease of the latter was significant (p less than 0.05). In both groups an increase in work tolerance could be demonstrated, but not in the "control group." In all three groups an improvement of lung function (IVC, FEV1) was found, but it was not significant in any of the groups. The small improvement might be due to a reduction in allergen exposure and better medical treatment. The study confirms the possibility of physical training of children with asthma even if exercise-induced asthmatic signs and symptoms are present. PMID:2263585

  14. Allergen skin test reactivities among asthmatic Thai children.

    PubMed

    Kongpanichkul, A; Vichyanond, P; Tuchinda, M

    1997-02-01

    Skin prick tests with 14 selected local aeroallergens were performed on 100 asthmatic children aged 0-16 years attending the Pediatric Allergy Clinic, Faculty of Medicine, Siriraj Hospital. The 14 allergens included Dermatophagoides farinae, Dermatophagoides pteronyssinus, American cockroach (Periplaneta americana), Johnson grass (Sorghum halopense), Cladosporium clarosporoides, Alternaria tenuis, Penicillium mix, Aspergillus mix, cat dander, dog dander, milk, egg white, soy and shrimp. Positive skin test reactivity was defined as a mean wheal diameter > or = 3 mm at the 20 minute reading. There were 68 males and 32 females. Their ages were between 0-2 years (n = 1), 2-5 years (n = 19), 5-10 years (n = 49) and 10-16 years (n = 31). Of all the subjects, 22 were classified as having mild asthma, 74 with moderate asthma and 4 with severe asthma. At least one skin prick test was positive in 74 subjects (74%) and two positive tests in 66 subjects (66%). The prevalence of sensitization to various allergens was as follows; Dermatophagoides pteronyssinus 67%, Dermatophagoides farinae 62%, American cockroach 44%, shrimp 14%, Johnson grass 14%, cat dander 10%, Alternaria 7%, Cladosporium 7%, dog dander 5%, soy 4%, Penicillium 3%, Aspergillus 2%, milk 2% and egg white 1%. The wheal size to Dermatophagoides pteronyssinus did not correlate with age. In this group of asthmatic Thai children, house dust mites are the most important allergen causing sensitization. PMID:9078689

  15. Mechanisms of BDNF regulation in asthmatic airway smooth muscle.

    PubMed

    Aravamudan, Bharathi; Thompson, Michael A; Pabelick, Christina M; Prakash, Y S

    2016-08-01

    Brain-derived neurotrophic factor (BDNF), a neurotrophin produced by airway smooth muscle (ASM), enhances inflammation effects on airway contractility, supporting the idea that locally produced growth factors influence airway diseases such as asthma. We endeavored to dissect intrinsic mechanisms regulating endogenous, as well as inflammation (TNF-α)-induced BDNF secretion in ASM of nonasthmatic vs. asthmatic humans. We focused on specific Ca(2+) regulation- and inflammation-related signaling cascades and quantified BDNF secretion. We find that TNF-α enhances BDNF release by ASM cells, via several mechanisms relevant to asthma, including transient receptor potential channels TRPC3 and TRPC6 (but not TRPC1), ERK 1/2, PI3K, PLC, and PKC cascades, Rho kinase, and transcription factors cAMP response element binding protein and nuclear factor of activated T cells. Basal BDNF expression and secretion are elevated in asthmatic ASM and increase further with TNF-α exposure, involving many of these regulatory mechanisms. We conclude that airway BDNF secretion is regulated at multiple levels, providing a basis for autocrine effects of BDNF under conditions of inflammation and disease, with potential downstream influences on contractility and remodeling. PMID:27317689

  16. [Continuous nebulization with terbutaline sulfate under tent inhalation. Evaluation of the efficacy in children 2 to 5 years of age in asthmatic crises].

    PubMed

    Lotufo, J P; Ejzenberg, B; Vieira, S; Mukai, L; Macedo, H; Yamashita, C; Ventura, G; Baldacci, E R; Okay, Y

    1998-06-01

    This study investigated the efficacy of a system for continuous nebulization of terbutaline sulphate in the treatment of acute asthmatic crises in children. The equipment consisted of a condensation nebulizer attached to a 40 liter acrylic tent placed around the patient's head. A prospective, randomized and open clinical trial was conducted. Twenty eight children, 2 to 5 year-old, in acute asthmatic crises were selected. Fourteen were nebulized with terbutaline sulphate while in the control group the aerosolization was proceeded only with half diluted physiologic serum. All patients were administered aminophyline intravenously. The parameter used to evaluate the efficacy of the terbutaline sulphate nebulizing system was clinical improvement measured by the Wood-Downes Score. Two additional parameters indicating terbutaline sulphate absorption were used: reduction of potassium seric levels and positive chronotropic effect. The group treated with terbutaline sulphate showed greater clinical improvement than control group at the 12 hour protocol evaluation as well as lower seric potassium level. A positive chronotropic effect was also observed at the final protocol evaluation. The data showed, preliminarily, that (a) the system for continuous nebulization of terbutaline sulphate was effective in treatment of children's acute asthmatic crises, and (b) there was evidence attesting to the absorption of terbutaline sulphate by the children treatment with it. PMID:9677633

  17. Evaluation of Trigeminal Sensitivity to Ammonia in Asthmatics and Healthy Human Volunteers

    PubMed Central

    Petrova, Maja; Diamond, Jeanmarie; Schuster, Benno; Dalton, Pamela

    2009-01-01

    Background Asthmatics often report the triggering or exacerbation of respiratory symptoms following exposure to airborne irritants, which in some cases may result from stimulation of irritant receptors in the upper airways inducing reflexive broncho-constriction. Ammonia (NH3) is a common constituent of commercially available household products, and in high concentration has the potential to elicit sensory irritation in the eyes and upper respiratory tract of humans. The goal of the present study was to evaluate the irritation potential of ammonia in asthmatics and healthy volunteers and to determine whether differences in nasal or ocular irritant sensitivity to ammonia between these two groups could account for the exacerbation of symptoms reported by asthmatics following exposure to an irritant. Methods 25 healthy and 15 mild/moderate persistent asthmatic volunteers, with reported sensitivity to household cleaning products, were evaluated for their sensitivity to the ocular and nasal irritancy of NH3. Lung function was evaluated at baseline and multiple time points following exposure. Results Irritation thresholds did not differ between asthmatics and healthy controls, nor did ratings of odor intensity, annoyance and irritancy following exposure to NH3 concentrations at and above the irritant threshold for longer periods of time (30 sec).Importantly, no changes in lung function occurred following exposure to NH3 for any individuals in either group. Conclusion Despite heightened symptom reports to environmental irritants among asthmatics, the ocular and nasal trigeminal system of mild-moderate asthmatics does not appear to be more sensitive or more reactive than that of non-asthmatics, nor does short duration exposure to ammonia at irritant levels induce changes in lung function. At least in brief exposures, the basis for some asthmatics to experience adverse responses to volatile compounds in everyday life may arise from factors other than trigeminally

  18. Omega-3 Fatty Acid Ethyl Esters do not Improve Clopidogrel Associated P2Y12 Inhibition in Stroke Patients

    PubMed Central

    Li, Ping; Kamal, Haris; Baxter, Melissa; Mehta, Bijal K.

    2015-01-01

    The specific action of omega-3 fatty acid ethyl esters (OFA) in preventing cerebrovascular disease remains unknown, but research has demonstrated multiple possible mechanisms. In addition to altering lipid profiles, OFA may inhibit platelet aggregation. Clopidogrel inhibits platelets via the P2Y12 receptor. OFA may alter clopidogrel-associated platelet-inhibition via a possible combined effect on P2Y12 inhibition. To determine if OFA affects clopidogrel associated P2Y12 platelet receptor inhibition by comparing the percentage of responders in patients with cerebrovascular disease who were taking clopidogrel with or without OFA. We retrospectively reviewed data from adult patients with cerebrovascular disease or cerebral aneurysms and taking clopidogrel, who were seen at a single hospital between March 2010 to September 2011. We included 438 subjects in the study. For the 67 subjects who received loading doses of both clopidogrel and OFA, 71.6% had a P2Y12 inhibition response more than 20%, which is considered a positive response. For the 55 subjects who received just clopidogrel load, 67.2% of subjects were responders. There were 70.4% responders in the 274 subjects who were taking 75 mg of clopidogrel alone at home, and 73.8% responders in the 42 subjects who were taking both clopidogrel and OFA at home. However, these percentage differences were not statistically significant. This study did not find additional P2Y12 platelet inhibition when patients were given OFA, either given as a loading dose or taking it daily. PMID:26294943

  19. Effect of inhaled beclomethasone dipropionate on isocapnic hyperventilation with cold air in asthmatics, measured with forced oscillation technique.

    PubMed

    Pennings, H J; Wouters, E F

    1997-03-01

    Isocapnic hyperventilation with cold air (IHCA) is a reliable technique for assessing indirect bronchial hyperresponsiveness in patients with asthma. Impedance measurement of the respiratory system by the forced pseudorandom noise oscillation technique is a sensitive technique to assess changes in bronchial tone after IHCA. The aim of this study was to evaluate the effect of 6 weeks of treatment with beclomethasone dipropionate, 1,000 microg x day-1, on IHCA in asthmatic patients, measured with both forced oscillation technique and flow-volume recordings. Forty patients with mild asthma were included in this double-blind, placebo-controlled parallel-group study. Stratification on the basis of sex was performed to overcome differences in airway diameter. At entry and every 2 weeks during the treatment period, IHCA was performed and patient diaries were evaluated. Characteristic changes in forced oscillation parameters after IHCA were observed in all patients. After 6 weeks of treatment, BDP-treated patients showed statistically significant differences in impedance measurements after IHCA, manifested by significant attenuation of resistance at 8 Hz (p<0.01), slope of the frequency-resistance curve (p<0.01), reactance at 8 Hz (p=0.01), and resonant frequency (f0) (p<0.02). Flow-volume recordings showed only a statistically significant change in the decrease of inspiratory vital capacity (IVC) (p=0.01). Furthermore, a significant correlation was observed between serum immunoglobulin E (IgE) levels and the effect of BDP on IHCA, measured with forced oscillation technique. In this study, beclomethasone dipropionate, 1,000 microg x day(-1) for 6 weeks, decreased indirect bronchial hyperresponsiveness as assessed by cold air bronchoprovocation in asthmatic patients. The forced oscillation technique proved a more sensitive method of detecting changes in bronchial tone than flow-volume recordings. PMID:9073002

  20. Day-to-day variation of bronchodilatory response to an inhaled beta-2-stimulant in asthmatics.

    PubMed

    Lindgren, S; Bake, B; Larsson, S

    1987-01-01

    The effect of inhaling 0.25 and 2.0 mg of terbutaline sulphate, a beta-2-stimulant, from a metered dose aerosol was studied in five asthmatic patients during two periods of five days each. During the first period, the patients used a good spontaneous inhalation technique; during the second period, the inhalation technique was optimized and controlled. The variation of basal FEV1 and of the increase (delta FEV1) caused by 0.25 mg of inhaled terbutaline was considerable. The effect was only slightly better and the variation only slightly smaller when the controlled inhalation technique was used. The differences were not significant. In individual patients, there was no or negative correlation between delta FEV1 and the corresponding basal FEV1 value. Accordingly, the most commonly used way of expressing delta FEV1 as a percentage of basal FEV1 value was found to be insensitive. Delta FEV1, expressed as a percentage of the maximum available FEV1 increase on the same day after 2.25 mg terbutaline sulphate, was found to be most sensitive. This way of expressing delta FEV1 will increase the possibilities of detecting differences between treatments in clinical trials. PMID:3453755

  1. Monosodium glutamate-induced asthma: study of the potential risk of 30 asthmatics and review of the literature.

    PubMed

    Moneret-Vautrin, D A

    1987-01-01

    Monosodium glutamate is a physiological nutrient, and food additive used as a taste enhancer. Several cases of intolerance to MSG in patients with asthma and with a Chinese Restaurant Syndrome have been published. A high dose of 2.5 g was tested in 6 healthy controls and 30 asthmatics (7: allergic asthma; 15: intrinsic asthma with intolerance to aspirin; 8: intrinsic asthma with aspirin intolerance, intolerance to alcohol or to food additives). Two patients presented with a mild bronchospasm, occurring 6 to 10 hours after the ingestion. Different mechanisms are discussed. A cholinergic mechanism might be incriminated, either due to stimulation of the synthesis of acetylcholine, or due to a vagal reflex elicited by a reflux esophagitis. However, a high vagal hyperreactivity seems to be needed for the occurrence of asthma. It is concluded that a very small subset of patients with intrinsic asthma might present with an intolerance to MSG if high doses are consumed. PMID:3331265

  2. The effect of marimastat, a metalloprotease inhibitor, on allergen-induced asthmatic hyper-reactivity

    SciTech Connect

    Bruce, Colleen; Thomas, Paul S. . E-mail: paul.thomas@unsw.edu.au

    2005-06-01

    This pilot study was designed to assess whether a synthetic matrix metalloproteinase (MMP) inhibitor has anti-inflammatory properties in mild asthma. Tumor necrosis factor alpha (TNF{alpha}) has been shown to be an important cytokine in the pathogenesis of allergic airway inflammatory responses, and its release can be inhibited by MMP inhibitors. Twelve atopic asthmatic subjects received the MMP inhibitor marimastat (5 mg) or placebo, twice daily for 3 weeks, separated by a 6-week washout period in a randomized, double-blind, cross-over manner. All subjects underwent an allergen inhalation provocation test to Dermatophagoides pteronyssinus before and after each study phase. Spirometry, exhaled NO (eNO) levels, differential sputum cell counts, an asthma symptom questionnaire, peak flow, and {beta}{sub 2}-agonist usage were measured. Nine subjects completed the study, and, when compared with placebo, marimastat reduced bronchial hyper-responsiveness to inhaled allergen in these subjects from an allergen PC{sub 20} of 22.2 AU/ml (95%CI 11.7-32.6) to 17.0 AU/ml (95%CI 7.6-26.4, P = 0.02). The marimastat phase showed a nonsignificant fall in sputum inflammatory cells. Marimastat did not modify eNO, FEV{sub 1}, asthma symptoms, or albuterol usage. In conclusion, airway responsiveness to allergen may be modified by a MMP inhibitor, perhaps via TNF{alpha} playing a role in airway inflammation and remodeling.

  3. The Immunoregulatory Effects of Traditional Chinese Medicine on Treatment of Asthma or Asthmatic Inflammation.

    PubMed

    Li, Jinyu; Zhang, Fuchun; Li, Jinyao

    2015-01-01

    Asthma is a chronic respiratory symptoms with variable airflow limitation and airway hyperresponsiveness (AHR), and causes high economic burden. Traditional Chinese medicine (TCM) has a long-lasting history of using herbal medicine in the treatment of various respiratory diseases including asthma. In the last several decades, an increasing number of herbs have been shown to be effective in the treatment of asthma in clinical trials or asthmatic inflammation in animal models. Literature about the effects of TCM on the immune system were searched in electronic databases such as PubMed, Google Scholar and Scopus from 2000 to 2014. 'TCM' and 'asthma' were used as keywords for the searches. Over 400 literatures were searched and the literatures about the immune system were selected and reviewed. We only reviewed literatures published in English. Accumulating evidence suggests that TCM can directly inhibit the activation and migration of inflammatory cells, regulate the balance of Th1/Th2 responses, and suppress allergic hyperreactivity through inducing regulatory T cells or attenuating the function of dendritic cells (DCs). These studies provided useful information to facilitate the use of TCM to treat asthma. This review was conducted to classify the findings based on their possible mechanisms of action reported. PMID:26364661

  4. The Effects of Uygur Herb Hyssopus officinalis L. on the Process of Airway Remodeling in Asthmatic Mice.

    PubMed

    Ma, Xiaojuan; Ma, Xiumin; Ma, Zhixing; Sun, Zhan; Yu, Wenyan; Wang, Jing; Li, Fengsen; Ding, Jianbing

    2014-01-01

    It has been proved that Uygur herb Hyssopus offcinalis L. could affect the levels of some cytokines (such as IL-4, IL-6, IL-17, and IFN-γ) in asthmatic mice. By detection of the expressions of MMP-9 and TIMP-1 and the morphological changes, the aim of this research is to reveal the mechanism of Uygur herb Hyssopus offcinalis L. in the process of airway remodeling. It was observed that the expressions of MMP-9 and TIMP-1 increased, but the ratio of MMP-9/TIMP-1 decreased in airway remodeling group. However, the expression of both MMP-9 and TIMP-1 decreased after being treated with dexamethasone and Hyssopus offcinalis L., accompanied by the relieved pathological changes, including collagen deposition, mucus secretion, and smooth muscle proliferation. It is suggested that Uygur herb Hyssopus offcinalis L. could inhibit airway remodeling by correcting imbalance of MMP-9/TIMP-1 ratio. PMID:25383084

  5. The Effects of Uygur Herb Hyssopus officinalis L. on the Process of Airway Remodeling in Asthmatic Mice

    PubMed Central

    Ma, Xiaojuan; Ma, Xiumin; Ma, Zhixing; Sun, Zhan; Yu, Wenyan; Wang, Jing; Li, Fengsen; Ding, Jianbing

    2014-01-01

    It has been proved that Uygur herb Hyssopus offcinalis L. could affect the levels of some cytokines (such as IL-4, IL-6, IL-17, and IFN-γ) in asthmatic mice. By detection of the expressions of MMP-9 and TIMP-1 and the morphological changes, the aim of this research is to reveal the mechanism of Uygur herb Hyssopus offcinalis L. in the process of airway remodeling. It was observed that the expressions of MMP-9 and TIMP-1 increased, but the ratio of MMP-9/TIMP-1 decreased in airway remodeling group. However, the expression of both MMP-9 and TIMP-1 decreased after being treated with dexamethasone and Hyssopus offcinalis L., accompanied by the relieved pathological changes, including collagen deposition, mucus secretion, and smooth muscle proliferation. It is suggested that Uygur herb Hyssopus offcinalis L. could inhibit airway remodeling by correcting imbalance of MMP-9/TIMP-1 ratio. PMID:25383084

  6. IgE anti Hepatitis B virus surface antigen antibodies detected in serum from inner city asthmatic and non asthmatic children.

    PubMed

    Smith-Norowitz, Tamar A; Tam, Elizabeth; Norowitz, Kevin B; Chotikanatis, Kobkul; Weaver, Diana; Durkin, Helen G; Bluth, Martin H; Kohlhoff, Stephan

    2014-04-01

    Viral Hepatitis type B (HBV) is a public health concern, but has not been linked to asthma. Immunoglobulin (Ig) G is involved in HBV immune responses; less is known about IgE antibodies (Abs) against HBV in asthma. Given the importance of HBV, we sought to determine whether HBV vaccine contributes to asthma in children, by stimulating specific IgE production. Total IgE, IgE- or IgG-anti-HBVs Abs were studied in vaccinated pediatric asthmatics and non asthmatics. We found: (1) total IgE was higher in asthmatics; (2) total IgE did not correlate with IgE anti-HBVs; (3) IgE anti-HBVs did correlate with IgG-anti-HBVs in all subjects; (4)IgE- and IgG-HBVs Abs were similar in both groups; (5) IgE- or IgG anti-HBVs Abs did not correlate with age. Our findings indicate that HBV vaccination induces IgE responses in asthmatics and non asthmatics. PMID:24374043

  7. Pneumomediastinum, subcutaneous emphysema and pneumorrhachis in asthmatic children.

    PubMed

    Colavita, L; Cuppari, C; Pizzino, M R; Sturiale, M; Mondello, B; Monaco, F; Barone, M; Salpietro, C

    2016-01-01

    Pneumomediastinum (PM), subcutaneous emphysema (SE) and pneumorrhachis (also known as epidural air (EDA) or epidural emphysema) are very rare findings in children. PM is defined as the passage of air from intra-alveolar space to interstitium and, later, to the mediastinum. From the mediastinum, the air may catch up subcutaneous tissue (usually of the neck) and/or epidural space via the cervical fascial planes and neural foramina, forming respectively SE and EDA. The PM can be divided in spontaneous (or idiopathic) and secondary PM. Only few studies have evaluated the exact incidence of PM and its complications in children, and to define the correct diagnostic work up, treatment and outpatient follow-up. We report the case of a 9-year-old child with undiagnosed asthma that, during severe asthmatic flare secondary to acute infection of high airway, developed PM, SE and EDA. PMID:27358152

  8. An antibody to amphiregulin, an abundant growth factor in patients' fluids, inhibits ovarian tumors.

    PubMed

    Carvalho, S; Lindzen, M; Lauriola, M; Shirazi, N; Sinha, S; Abdul-Hai, A; Levanon, K; Korach, J; Barshack, I; Cohen, Y; Onn, A; Mills, G; Yarden, Y

    2016-01-28

    Growth factors of the epidermal growth factor (EGF)/neuregulin family are involved in tumor progression and, accordingly, antibodies that intercept a cognate receptor, epidermal growth factor receptor (EGFR)/ERBB1, or a co-receptor, HER2, have been approved for cancer therapy. Although they might improve safety and delay onset of chemoresistance, no anti-ligand antibodies have been clinically approved. To identify suitable ligands, we surveyed fluids from ovarian and lung cancer patients and found that amphiregulin (AREG) is the most abundant and generalized ligand secreted by advanced tumors. AREG is a low affinity EGFR ligand, which is upregulated following treatment with chemotherapeutic drugs. Because AREG depletion retarded growth of xenografted ovarian tumors in mice, we generated a neutralizing monoclonal anti-AREG antibody. The antibody inhibited growth of ovarian cancer xenografts and strongly enhanced chemotherapy efficacy. Taken together, these results raise the possibility that AREG and other low- or high-affinity binders of EGFR might serve as potential targets for cancer therapy. PMID:25915843

  9. Rhinovirus upper respiratory infection increases airway hyperreactivity and late asthmatic reactions.

    PubMed Central

    Lemanske, R F; Dick, E C; Swenson, C A; Vrtis, R F; Busse, W W

    1989-01-01

    Although viral upper respiratory infections (URIs) provoke wheezing in many asthma patients, the effect of these illnesses on the airway response to inhaled antigen is not established. The following study evaluated the effect of an experimental rhinovirus (RV) illness on airway reactivity and response to antigen in 10 adult ragweed allergic rhinitis patients. Preinfection studies included measurements of airway reactivity to histamine and ragweed antigen. Furthermore, the patients were also evaluated for late asthmatic reactions (LARs) to antigen (a 15% decrease in forced expiratory volume of the first second approximately 6 h after antigen challenge). 1 mo after baseline studies, the patients were intranasally inoculated with live RV16. All 10 patients were infected as evidenced by rhinovirus recovery in nasal washings and respiratory symptoms. Baseline FEV1 values were stable throughout the study. During the acute RV illness, there was a significant increase in airway reactivity to both histamine and ragweed antigen (P = 0.019 and 0.014, respectively). Before RV inoculation, only 1 of the 10 subjects had an LAR after antigen challenge. However, during the acute RV illness, 8 of 10 patients had an LAR (P less than 0.0085 compared with baseline); the development of LARs was independent of changes in airway reactivity and the intensity of the immediate response to antigen. Therefore, we found that not only does a RV respiratory tract illness enhance airway reactivity, but it also predisposes the allergic patient to develop LARs, which may be an important factor in virus-induced bronchial hyperresponsiveness. PMID:2536042

  10. Impaired Bronchoprotection Is Not Induced by Increased Smooth Muscle Mass in Chronic Treatment In Vivo with Formoterol in Asthmatic Mouse Model

    PubMed Central

    Luo, W; Liu, C-T; Yang, Q-H; Yu, Q; Wang, T

    2014-01-01

    ABSTRACT Objective: Inhaling β2-adrenoceptor agonist is first-line asthma treatment, which is used for both acute relief of and prevention of bronchoconstriction. However, chronic use of β-agonists results in impaired bronchoprotection and increasing occurrences of severe asthma exacerbation, even death in clinical practice. The mechanism of β-adrenoceptor hyposensitivity has not been thoroughly elucidated thus far. Bronchial smooth muscle contraction induces airway narrowing and also mediates airway inflammation. Moreover, bronchial smooth muscle mass significantly increases in asthmatics. We aim to establish an asthmatic model that demonstrated that formoterol induced impaired bronchoprotection and to see whether increased smooth muscle mass played a role in it. Methods: We combined routine allergen challenging (seven weeks) with repeated application of formoterol, formoterol plus budesonide or physiological saline in allergen-sensitized BALB/c mouse. The bronchoprotection mediated by β-agonist was measured in five consecutive weeks. Smooth muscle mass was shown by morphometric analysis, and α-actin expression was detected by western blot. Results: The trend of bronchoprotection was wavy in drug interventional groups, which initially increased and then decreased. Chronic treatment with formoterol significantly impaired bronchoprotection. According to the morphometric analysis and α-actin expression, no significant difference was detected in smooth muscle mass in all groups. Conclusion: This experiment successfully established that a chronic asthmatic mouse model, which manifested typical features of asthmatic patients, when treated chronically with formoterol, showed a loss of bronchoprotection. No significant difference was detected in smooth muscle mass in all groups, which implied some subcellular signalling changes may be the key points. PMID:25803396

  11. AMBIENT COARSE PARTICULATE MATTER ASSOCIATED WITH HEMATOLOGIC FACTORS IN ADULT ASTHMATICS

    EPA Science Inventory

    Introduction: The elderly and those with cardiovascular disease are susceptible to particulate matter (PM) exposures. Asthmatics are thought to be primarily affected by PM via airway inflammation. We investigated whether factors in blood hemostasis change in response to fluctuat...

  12. ACUTE RESPIRATORY HEALTH EFFECTS OF AIR POLLUTION ON ASTHMATIC CHILDREN IN US INNER CITIES

    EPA Science Inventory

    Introduction: Asthmatic children living in inner-city communities are a particularly vulnerable subgroup, both because of their underlying airways disease and their exposure to relatively high levels of motor vehicle emissions.
    Objective: To investigate the association betw...

  13. Influenza enhances caspase-1 in bronchial epithelial cells from asthmatic volunteers and is associated with pathogenesis

    EPA Science Inventory

    Background: The leading cause of asthma exacerbation is respiratory viral infection. Innate antiviral defense pathways are altered in the asthmatic epithelium, yet involvement of inflammasome signaling in virus-induced asthma exacerbation is not known. Objective: This study com...

  14. Sodium-glucose cotransporter 2 inhibition and cardiovascular risk reduction in patients with type 2 diabetes: the emerging role of natriuresis.

    PubMed

    Rajasekeran, Harindra; Lytvyn, Yuliya; Cherney, David Z I

    2016-03-01

    Inhibition of sodium-glucose cotransporter 2 causes both glycosuria and natriuresis, leading to reductions in hyperglycemia, body weight, blood pressure, and proteinuria. The recently published EMPA-REG OUTCOME study demonstrated significant cardiovascular and mortality benefits of sodium-glucose cotransporter 2 inhibition with empagliflozin in patients with type 2 diabetes and established cardiovascular disease, and may suggest a broader role for sodium-glucose cotransporter 2 inhibition in patients with heart failure. PMID:26880444

  15. The effect of exercise in the asthmatic child - its clinical implications.

    PubMed

    Van Niekerk, C H

    1977-09-01

    Appropriate exercise will provoke an attack of bronchospasm in virtually all asthmatic children. Exercise-induced asthma can effectively be prevented by pre-exercise treatment with sympathomimetic drugs or sodium cromoglycate, and there is no reason why an asthmatic should not participate in sporting activities. Running at a steady pace for 6 - 8 minutes (submaximal effort) is the most asthmagenic exercise, whereas swimming is the least athmagenic. PMID:918785

  16. Classification of Impulse Oscillometric Patterns of Lung Function in Asthmatic Children using Artificial Neural Networks.

    PubMed

    Barua, Miroslava; Nazeran, Homer; Nava, Patricia; Diong, Bill; Goldman, Michael

    2005-01-01

    Impulse Oscillometry (IOS) is an innovative patient-friendly pulmonary testing technique which measures the respiratory system impedance (Z) by using the spectral components of pressure to flow ratio which yields resistance and reactance values at different frequencies. The high dimensionality of IOS measurement data makes the analysis of this information difficult. Artificial Neural Networks (ANNs) are mathematical models composed of a large number of highly interconnected neurons that are able to learn and generalize from data. An ANN-based approach to the analysis of IOS data can potentially provide an efficient and automatic method to recognize and classify pulmonary diseases. This would help characterize major respiratory illnesses such as asthma based on IOS measurements. Asthma can be difficult to diagnose, because the symptoms are sometimes similar to other lung conditions. A data set composed of 361 impulse oscillometric patterns from asthmatic children was used in this study. The ANN was capable of distinguishing between relatively constricted and nonconstricted airway conditions in these patients. Using all of the 361 patterns during training as well as in the feed-forward stage, a classification accuracy of 95.01% was obtained for validation. When the ANN was presented with only 60% of the original 361 patterns in the data set during training and with the remaining 40% as unseen patterns, the generalization stage, a classification accuracy of 98.61% was achieved. PMID:17282180

  17. Flagellin Modulates the Function of Invariant NKT Cells From Patients With Asthma via Dendritic Cells

    PubMed Central

    Shim, Jae-Uoong; Rhee, Joon-Haeng; Jeong, Ji-Ung

    2016-01-01

    Purpose Invariant natural killer T (iNKT) cells play a critical role in the pathogenesis of asthma. We previously reported the association between circulating Th2-like iNKT cells and lung function in asthma patients and the suppressive effect of Toll-like receptor 5 ligand flagellin B (FlaB) on asthmatic in a mouse model. Thus, we investigated whether FlaB modulates the function of circulating iNKT cells in asthmatic patients. Methods Peripheral blood mononuclear cells (PBMCs) were treated with FlaB, and the secreted and intracellular cytokines of iNKT cells were evaluated by using ELISA and flow cytometry, respectively, following stimulation with α-galactosylceramide. Foxp3+ iNKT cells were also measured. To determine the effect of FlaB-treated dendritic cells (DCs) on iNKT cells, we co-cultured CD14+ monocyte-derived DCs and T cells from patients with house dust mite-sensitive asthma and analyzed intracellular cytokines in iNKT cells. Results A reduction of IL-4 and IL-17 production by iNKT cells in PBMCs after FlaB treatment was alleviated following blocking of IL-10 signaling. A decrease in the frequencies of IL-4+ and IL-17+ iNKT cells by FlaB-treated DCs was reversed after blocking of IL-10 signaling. Simultaneously, an increase in Foxp3+ iNKT cells induced by FlaB treatment disappeared after blocking of IL-10. Conclusions FlaB may inhibit Th2- and Th17-like iNKT cells and induce Foxp3+ iNKT cells by DCs via an IL-10-dependent mechanism in asthmatic patients. In patients with a specific asthma phenotype associated with iNKT cells, FlaB may be an effective immunomodulator for iNKT cell-targeted immunotherapy. PMID:26922930

  18. Paired-Pulse Inhibition in the Auditory Cortex in Parkinson's Disease and Its Dependence on Clinical Characteristics of the Patients

    PubMed Central

    Lukhanina, Elena; Berezetskaya, Natalia; Karaban, Irina

    2011-01-01

    We aimed to determine the value of the paired-pulse inhibition (PPI) in the auditory cortex in patients with Parkinson's disease (PD) and analyze its dependence on clinical characteristics of the patients. The central (Cz) auditory evoked potentials were recorded in 58 patients with PD and 22 age-matched healthy subjects. PPI of the N1/P2 component was significantly (P < .001) reduced for interstimulus intervals 500, 700, and 900 ms in patients with PD compared to control subjects. The value of PPI correlated negatively with the age of the PD patients (P < .05), age of disease onset (P < .05), body bradykinesia score (P < .01), and positively with the Mini Mental State Examination (MMSE) cognitive score (P < .01). Negative correlation between value of PPI and the age of the healthy subjects (P < .05) was also observed. Thus, results show that cortical inhibitory processes are deficient in PD patients and that the brain's ability to carry out the postexcitatory inhibition is age-dependent. PMID:21052541

  19. Lateral Inhibition in the Human Visual System in Patients with Glaucoma and Healthy Subjects: A Case-Control Study

    PubMed Central

    Junoy Montolio, Francisco G.; Meems, Wilma; Janssens, Marieke S. A.; Stam, Lucas; Jansonius, Nomdo M.

    2016-01-01

    In glaucoma, the density of retinal ganglion cells is reduced. It is largely unknown how this influences retinal information processing. An increase in spatial summation and a decrease in contrast gain control and contrast adaptation have been reported. A decrease in lateral inhibition might also arise. This could result in a larger than expected response to some stimuli, which could mask ganglion cell loss on functional testing (structure-function discrepancy). The aim of this study was to compare lateral inhibition between glaucoma patients and healthy subjects; we used a case-control design. Cases (n = 18) were selected to have advanced visual field loss in combination with a normal visual acuity. Controls (n = 50) were not allowed to have symptoms or signs of any eye disease. Lateral inhibition was measured psychophysically on a computer screen, with (1) a modified illusory movement experiment and (2) a contrast sensitivity (CS) test. Illusory movement was quantified by nulling it with a real movement; measure of lateral inhibition was the amount of illusory movement. CS was measured at 1 and 4 cycles per degree (cpd); measure of lateral inhibition was the difference between log CS at 4 and 1 cpd. Both measures were compared between cases and controls; analyses were adjusted for age and gender. There was no difference between cases and controls for these two measures of lateral inhibition (p = 0.58 for illusory movement; p = 0.20 for CS). The movement threshold was higher in cases than in controls (p = 0.008) and log CS was lower, at both 1 (-0.20; p = 0.008) and 4 (-0.28; p = 0.001) cpd. Our results indicate that spatially antagonistic mechanisms are not specifically affected in glaucoma, at least not in the intact center of a severely damaged visual field. This suggests that the structure-function discrepancy in glaucoma is not related to a decrease in lateral inhibition. PMID:26953590

  20. Lateral Inhibition in the Human Visual System in Patients with Glaucoma and Healthy Subjects: A Case-Control Study.

    PubMed

    Junoy Montolio, Francisco G; Meems, Wilma; Janssens, Marieke S A; Stam, Lucas; Jansonius, Nomdo M

    2016-01-01

    In glaucoma, the density of retinal ganglion cells is reduced. It is largely unknown how this influences retinal information processing. An increase in spatial summation and a decrease in contrast gain control and contrast adaptation have been reported. A decrease in lateral inhibition might also arise. This could result in a larger than expected response to some stimuli, which could mask ganglion cell loss on functional testing (structure-function discrepancy). The aim of this study was to compare lateral inhibition between glaucoma patients and healthy subjects; we used a case-control design. Cases (n = 18) were selected to have advanced visual field loss in combination with a normal visual acuity. Controls (n = 50) were not allowed to have symptoms or signs of any eye disease. Lateral inhibition was measured psychophysically on a computer screen, with (1) a modified illusory movement experiment and (2) a contrast sensitivity (CS) test. Illusory movement was quantified by nulling it with a real movement; measure of lateral inhibition was the amount of illusory movement. CS was measured at 1 and 4 cycles per degree (cpd); measure of lateral inhibition was the difference between log CS at 4 and 1 cpd. Both measures were compared between cases and controls; analyses were adjusted for age and gender. There was no difference between cases and controls for these two measures of lateral inhibition (p = 0.58 for illusory movement; p = 0.20 for CS). The movement threshold was higher in cases than in controls (p = 0.008) and log CS was lower, at both 1 (-0.20; p = 0.008) and 4 (-0.28; p = 0.001) cpd. Our results indicate that spatially antagonistic mechanisms are not specifically affected in glaucoma, at least not in the intact center of a severely damaged visual field. This suggests that the structure-function discrepancy in glaucoma is not related to a decrease in lateral inhibition. PMID:26953590

  1. Effects fo sulfuric acid aerosol on respiratory mechanics and mucociliary particle clearance in healthy and asthmatic adults

    SciTech Connect

    Leikauf, G.D.

    1981-01-01

    The effects of submicrometer sulfuric acid (H/sub 2/SO/sub 4/) aerosol on human pulmonary physiology were investigated. Eighteen healthy and 10 asthmatic subjects inhaled H/sub 2/SO/sub 4/ via nasal mask for 1 hour at concentrations of 0, 100, 300 and 1000 ..mu..g/m/sup 3/ in a random sequence. The aerosol size (0.5 ..mu..m) and lower exposure level (100 ..mu..g/m/sup 3/) were selected to simulate peak ambient conditions, while the upper exposure concentration (1000 ..mu..g/m/sup 3/) is comparable to the current occupational limit for chronic exposure. Bronchial mucociliary clearance was markedly altered in all but one of the healthy subjects following one or more of the H/sub 2/SO/sub 4/ inhalations. The mucus was tagged by having each subject inhale either a 7.6 or 4.2 ..mu..m radiolabeled Fe/sub 2/O/sub 3/ aerosol. Exposure to 1000 ..mu..g/m/sup 3/ H/sub 2/SO/sub 4/ produced a delay in clearance which lasted longer in the group of eight inhaling the smaller 4.2 ..mu..m Fe/sub 2/O/sub 3/ aerosol than in the group of ten inhaling 7.6 ..mu..m Fe/sub 2/O/sub 3/. At 100 ..mu..g/m/sup 3/, the groups differed to a greater extent with clearance of the more centrally deposited larger aerosol being stimulated and that of the distally deposited smaller aerosol being transiently inhibited. Tracheal clearance remained unchanged in both groups. These findings, along with calculations of the various aerosols' deposition patterns, indicate that H/sub 2/SO/sub 4/ exerted a greater effect in the distal airways than in the proximal airways. Slight changes in ventilatory mechanics were noted in the asthmatic subjects following the 1000 ..mu..g/m/sup 3/ H/sub 2/SO/sub 4/ exposure, an effect not observed in the healthy subjects. However, the results obtained in the asthmatic group for tests of mucociliary clearance failed to reach significance, possible due to the large variability of such measurements in groups with respiratory disease.

  2. Does adding noradrenaline reuptake inhibition to selective serotonin reuptake inhibition improve efficacy in patients with depression? A systematic review of meta-analyses and large randomised pragmatic trials.

    PubMed

    Bradley, Andrew J; Lenox-Smith, Alan J

    2013-08-01

    Selective serotonin reuptake inhibitors (SSRIs) are recommended as first-line pharmacological treatment for depression and are the most commonly prescribed class of antidepressants. However, there is substantial evidence that noradrenaline has a role in the pathogenesis and treatment of depression. This review aims to examine the evidence of including noradrenaline reuptake inhibition with serotonin reuptake inhibition with respect to increasing efficacy in the treatment of depression. Evidence from meta-analysis of randomised controlled trials (RCTs) and randomised pragmatic trials was found in support of greater efficacy of the serotonin noradrenaline reuptake inhibitors (SNRIs), venlafaxine and duloxetine, in moderate to severe depression compared to SSRIs but no evidence was found for superiority of milnacipran. There is sufficient current evidence that demonstrates an increase in efficacy, when noradrenaline reuptake is added to serotonin (5-HT) reuptake, to suggest that patients with severe depression or those who have failed to reach remission with a SSRI may benefit from treatment with a SNRI. However, as these conclusions are drawn from the evidence derived from meta-analyses and pragmatic trials, large adequately powered RCTs using optimal dosing regimens and clinically relevant outcome measures in severe depression and SSRI treatment failures are still required to confirm these findings. PMID:23832963

  3. Multi-pollutant exposures in an asthmatic cohort

    NASA Astrophysics Data System (ADS)

    Williams, Ron; Rappold, Ana G.; Case, Martin; Schmitt, Mike; Stone, Susan; Jones, Paul; Thornburg, Jonathan; Devlin, Robert B.

    2012-12-01

    An investigation of personal fine and coarse particulate matter (PM2.5, PM10-2.5), nitrogen dioxide (NO2), and ozone (O3) exposures was conducted with an adult asthmatic cohort as part of the U.S. Environmental Protection Agency's Moderate and Severe Asthmatics and their Environment Study (MASAES). The overall goal of the MASAES was to determine the association of particulate matter on the degree of resulting lung inflammation, with those having severe asthma hypothesized to be more highly susceptible to such outcomes. The primary exposure objective was to determine the spatial (personal versus ambient) and temporal relationships associated with the aforementioned air pollutants and establish the precision of a new dual PM2.5, PM10-2.5 monitor (CPEM) for personal exposure monitoring. A total of 16 non-smoking adults of various asthma severities were monitored over the course of a 14 month period during 2008-2009. Participants were monitored for 24 continuous hours each monitoring day with a maximum of five events per participant. Median personal PM2.5 and PM10-2.5 exposures were 16.5 and 10.1 μg m-3, respectively. Daily ambient mass concentrations accounted for less than 1% of the observed variability in personal PM2.5 or PM10-2.5 exposures. Duplicate personal measures yielded R2 values of 0.92 PM2.5 and 0.77 PM10-2.5, respectively. Maximum daily personal exposures of 17.0 ppb NO2 and 21.7 ppb O3 occurred with respective mean exposures of 5.8 and 3.4 ppb. Ambient NO2 and O3 measures were observed to be poorly associated with personal exposures (R2 < 0.08) when viewed independent of the participant. The poor correlation between personal and ambient concentrations of PM as well as the various gaseous copollutants indicates the complexity of the multi-pollutant environment and the impact of non-ambient sources on these pollutants relative to total personal exposures.

  4. Evaluation of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy.

    PubMed

    Harmanci, Koray; Razi, Cem H; Toyran, Muge; Kanmaz, Gozde; Cengizlier, Mehmet R

    2010-03-01

    Specific immunotherapy (SIT) is one of the treatment modalities recomended for the management of asthma and allergic rhinitis by international guidelines. A potential benefit of immunotherapy (IT) is to prevent the development of sensitisation to new allergens. There is stil no conclusion on this subject. One hundred twenty-two children 8-18 years old with intermittent asthma, with or without allergic rhinitis, all of whom were monosensitised to house dust mite (HDM) were selected. Sixty two of these children accepted to receive SIT with HDM extract for 4 years and the remaining 60 did not accept SIT and were treated with asthma medications only. This second group of children served as the control group. At the end of the 4-year study period, 36 of the 53 patients (67.9%) in the SIT group showed no new sensitizations, compared to 38 of 52 (73.0%) in the control group (p = 0.141). The most frequent new sensitizations at the end of the study were pollens, grasses and olive polen, followed by animal dander, alternaria and cockroach. In conclusion, SIT may not prevent the onset of new sensitizations in asthmatic children monosensitized to house dust mites. Further investigation is required to clarify the immunologic mechanisms and other factors by which SIT reduces or not the development of new sensitizations in monosensitized children. PMID:20527510

  5. Complementary and Alternative Medication Use and Adherence to Inhaled Corticosteroid Among Inner-city Asthmatics

    PubMed Central

    Roy, Angkana; Lurslurchachai, Linda; Halm, Ethan A.; Li, Xiu-Min; Wisnivesky, Juan P.

    2009-01-01

    Background Complementary and alternative medicines (CAM) are used widely by patients with chronic diseases such as asthma. However, it is unclear whether use of CAM is associated with decreased adherence to inhaled corticosteroids (ICS), a key component of asthma management. Methods We surveyed 326 adults with persistent asthma receiving care at two inner-city outpatient clinics. Patients were asked about CAM use for treatment of asthma in the prior six months. Medication adherence was assessed using the Medication Adherence Report Scale, a validated self-report measure. Univariate and multiple regression analyses were used to assess the relationship between CAM use, adherence to ICS, and medication and disease beliefs. Results Overall, 25% (95% CI: 20–30%) of patients reported CAM use. Of those who used CAM, 39% (95% CI: 19–59%) discussed it with their physician, and 21% (95% CI: 12–31%) used CAM in place of prescribed asthma therapy. Univariate analyses showed that CAM use was associated with decreased ICS adherence and increased asthma morbidity. In multivariable analysis, CAM use was associated with lower ICS adherence (odds ratio [OR]: 0.5, 95% CI: 0.3–0.9) after adjusting for age, gender, race/ethnicity, education, years since diagnosis, language, and co-morbidities. CAM users were also more likely to worry about side effects of ICS (p=0.01). Conclusion CAM use was associated with decreased ICS adherence among inner-city asthmatics. Medication beliefs such as worry about ICS side effects may in part mediate this relationship. CAM use may be a marker for decreased adherence to ICS, particularly among patients with poor asthma control. PMID:20306816

  6. Interference of anti-inflammatory and anti-asthmatic drugs with neutrophil-mediated platelet activation: singularity of azelastine.

    PubMed Central

    Renesto, P.; Balloy, V.; Vargaftig, B. B.; Chignard, M.

    1991-01-01

    1. The capacity of various drugs (acetylsalicylic acid (ASA), ketoprofen, diclofenac, piroxicam, BW 755C, BW A4C, nedocromil sodium and azelastine) to inhibit human polymorphonuclear neutrophil (PMN)-mediated platelet activation was investigated. In this model, stimulated PMN release cathepsin G (Cat G), a serine proteinase which, in turn, induces platelet activation. 2. Among the different tested drugs, azelastine (100 microM for 1 min) was the only one able to prevent platelet aggregation. The cyclo-oxygenase inhibitors were all inactive, although used at effective concentrations as judged by inhibition of thromboxane B2 (TxB2) formation. Inhibition of platelet aggregation by azelastine was concentration-dependent, the range of active concentrations being of 20-70 microM. Release from platelets of 5-hydroxytryptamine was also inhibited at 30 microM and above, but never reached 100%. 3. The inhibition by azelastine is due to an effect on both cells. Indeed, beta-glucuronidase release from activated PMN and platelet activation by purified Cat G were both affected. 4. However, used at high concentrations (greater than 100 microM) azelastine was toxic since it released significant amounts of lactate dehydrogenase (LDH) from PMN and platelets. 5. These results show the capacity of azelastine, an anti-allergic and anti-asthmatic compound, to inhibit the cell-to-cell communication between PMN and platelets, an effect which may be relevant for its therapeutic efficacy or for a new application in diseases in which PMN and platelets are involved. PMID:1653073

  7. Comparison of P2Y12 receptor inhibition by clopidogrel and prasugrel in patients undergoing percutaneous coronary intervention.

    PubMed

    Haq, M M; Ahsan, C H; Amin, M N; Karim, M R; Ali, M L; Khan, S R; Chowdhury, M Z; Mansur, M; Millat, M H; Rashid, M A

    2013-12-01

    Dual antiplatelet treatment (DAPT) with aspirin and clopidogrel is vital after percutaneous coronary intervention (PCI). Clopidogrel and prasugrel act on P2Y12 platelet surface receptors. Both these P2Y12 inhibitors are pro-drugs and depend on cytochrome system of the liver for their conversion to active metabolite. There is growing concern regarding suboptimal response in platelet inhibition by clopidogrel. Verify Now system got approval by Federal Drug Administration, USA, for assessing platelet function as its result is almost comparable to gold standard Light Transmission Aggregometry (LTA). There are no data on the prevalence of clopidogrel resistance in Bangladeshi population. Prasugrel, as an antiplatelet drug, is a newer introduction in this country. This study will show light on the efficacy of these drugs on our population especially in patients who undergo PCI where DAPT is mandatory. A total 120 (60 diabetics) patients with Acute Coronary Syndrome (ACS), were alternatively given 600 mg clopidogrel loading dose (LD) followed by 75 mg maintenance dose (MD) daily or 60 mg LD of prasugrel followed by 10 mg MD daily. Five samples of blood were taken at different time intervals over a period of 2 weeks. Measurement of percent inhibition of P2Y12 was done by VerifyNow. Patients who showed less than 20% inhibition (clopidogrel resistant) at any stage were switched to prasugrel. The outcomes of clopidogrel, prasugrel and clopidogrel switched to prasugrel groups were then compared. Nearly half (46.7%) of the patients in the clopidogrel group was found resistant to the drug as opposed to none in the prasugrel group. No difference was found between diabetic and non-diabetic subjects with respect to drug resistance. Intracoronary blood samples showed high degree of platelet inhibition with prasugrel. There was a gradual decline of platelet inhibition over two weeks with prasugrel. Almost fifty percent of the population is clopidogrel resistant in our study

  8. Knowledge of asthma among parents of asthmatic children.

    PubMed

    Lal, A; Kumar, L; Malhotra, S

    1995-06-01

    The knowledge and attitude towards asthma, of parents, of 85 asthmatic children was assessed using a 17 item questionnaire. Results showed that 34.1% believed asthma to be contagious, 48.2% of the parents hesitated in referring to their child's illness as asthma. Other commonly held beliefs were that asthma is a life long illness (35.3%); food items are important precipitating factors for acute attacks (88.2%); mild exacerbations need to be treated with bronchodilators (6.3%); bronchodilators should be started at home before consulting a physician in case of an acute attack (61.2%); and cure of asthma is possible through modern drugs (30.6%) or through alternative systems of medicine (65%). Ninety one per cent of parents lacked an awareness of the side effects of anti-asthma medication. It is concluded that parental education through improved physician parent communication is necessary for enhancing the quality of care being provided to children with asthma, a fact also highlighted by the International Consensus Report on Management of Asthma. PMID:8613333

  9. Upstream mitogen-activated protein kinase (MAPK) pathway inhibition: MEK inhibitor followed by a BRAF inhibitor in advanced melanoma patients.

    PubMed

    Goldinger, Simone M; Zimmer, Lisa; Schulz, Carsten; Ugurel, Selma; Hoeller, Christoph; Kaehler, Katharina C; Schadendorf, Dirk; Hassel, Jessica C; Becker, Juergen; Hauschild, Axel; Dummer, Reinhard

    2014-01-01

    BRAF-mutant melanoma can be successfully treated by BRAF kinase inhibitors (BRAFi) and MEK kinase inhibitors (MEKi). However, the administration of BRAFi followed by MEKi did not generate promising response rate (RR). The purpose of this investigation was to evaluate the time to progression (TTP) with a mitogen-activated protein kinase (MAPK) pathway upstream inhibition strategy in BRAF mutated melanoma patients. BRAF mutation positive metastatic melanoma patients were identified within the Dermatology Cooperative Oncology Group (DeCOG) network and were treated first with a MEKi and upon progression with a selective BRAFi. A total of 23 melanoma patients (six females, 17 males, aged 47-80 years) were retrospectively analysed for TTP. The total median TTP was 8.9 months. The median TTP for MEKi was 4.8 (1.2-23.2) and subsequent for BRAFi 4.5 (1.2-15.7) months, respectively. A higher RR for MEKi (39%, nine partial responses and 0 complete responses) than previously reported was observed. Our analysis suggests that the reversed inhibition of the MAPK pathway is feasible in BRAF mutated melanoma. The median TTP (8.9 months) is close to the promising BRAF- and MEKi combination therapy (median progression-free survival (PFS) 9.4 months). The total treatment duration of the MAPK inhibition when a MEKi is administered first is similar compared to the reversed sequence, but TTP shifts in favour to the MEKi. This approach is feasible with reasonable tolerability. This clinical investigation encourages further studies in prospective clinical trials to define the optimal treatment schedule for the MAPK pathway inhibition and should be accompanied by molecular monitoring using repeated biopsies. PMID:24183461

  10. Efficacies of immunotherapy with polypeptide vaccine from ProDer f 1 in asthmatic mice

    PubMed Central

    Li, Chaopin; Li, Qiuyu; Jiang, Yuxin

    2015-01-01

    Allergic asthma is associated with the major house dust mite group 1 allergens Der p 1 and Der f 1, which belongs to the papin-like protease family and is the most potent of indoor allergens and allergen-specific immunotherapy (SIT), is seen as effective intervention for the entity. The current study was designed to verify the SIT efficacies of the enzymatic hydrolysates (papain and trypsin) in mice with asthma. We initially developed the asthmatic mouse models with ProDer f 1, and respectively applied recombinant ProDer f 1 protein and the two kinds of enzymatic hydrolysates for SIT. The results were verified by measuring the contents of IL-4, IL-10, IL-17 and IFN-γ changed in both bronchoalveolar lavage fluid (BALF) and supernatant of splenocyte culture as well as level changes of specific IgE and IgG2a in the serum. After SIT intervention, the symptoms of allergic inflammation was alleviated significantly in mice treated with ProDer f 1 protein and the two enzymatic hydrolysates via detection of the lung tissue sections, and infiltration of inflammatory cells was also notably depressed as compared with the models, though the epithelial structure in airways remained similar with the PBS group. In addition, we observed lower serum contents of the specific IgE antibody and lower levels of IL-4, IL-17 in BALF and splenic cells in mice undergone SIT, whereas specific IgG2a, IFN-γ and IL-10 in BALF and supernatant of splenocyte culture were higher as compared to the asthma group. The findings suggest the SIT using the above two kinds of hydrolysates may effectively inhibit the allergic inflammation in the airways of mouse models sensitized with ProDer f 1 protein. PMID:25932130

  11. Cytokine profiling in exhaled breath condensate after exercise challenge in asthmatic children with post-exercise symptoms

    PubMed Central

    Majak, Paweł; Jerzyńska, Joanna; Bojo, Magdalena; Brzozowska, Agnieszka; Koczkowska, Magdalena; Sielski, Piotr; Stelmach, Włodzimierz; Stelmach, Rafał; Janas, Anna

    2016-01-01

    Introduction Markers of exhaled breath condensate (EBC) correlate with lung function impairment, airway remodeling and different aspects of the disease such as exercise-induced bronchoconstriction (EIB). Aim of the study was to determine the cytokine profile in EBC of children with asthma after an exercise treadmill challenge in order to obtain clinically useful information about mechanisms of EIB; also, to assess correlations between cytokine concentrations in EBC and clinical characteristics of the patients. Material and methods The study population consisted of 25 randomly selected children, aged 8 to 19 years, with asthma and EIB symptoms despite the use of control medications. Patients on the day of the study visit underwent fractional exhaled nitric oxide measurement (FeNO) and baseline spirometry, performed an exercise treadmill challenge (ETC), and EBC samples were obtained at the end of the ETC. Results In asthmatic children with positive ETC, monocyte hemotactic protein-1 (MCP-1) and IL-16 adjusted to pre-EBC forced expiratory volume in 1 s (FEV1) were significantly higher compared to children with negative ETC (p = 0.022 and p = 0.017 respectively). After adjustment to pre-EBC FEV1 other cytokines (IL-4, IL-5, IL-6, IL-8, MIG, TNF-α) were not related to post-exercise changes in FEV1. Conclusions We observed a specific inflammatory profile in the airways of asthmatic children with bronchoconstriction induced by exercise. The concentration of cytokines in EBC depended on the post-exercise decrease in FEV1, which was measured by the area under the curve (AUC). MCP-1 and IL-16, adjusted to pre-EBC FEV1, were significantly higher in children with a positive exercise challenge compared to those with a negative one. PMID:27478459

  12. Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel.

    PubMed

    Stenfors, N; Nordenhäll, C; Salvi, S S; Mudway, I; Söderberg, M; Blomberg, A; Helleday, R; Levin, J O; Holgate, S T; Kelly, F J; Frew, A J; Sandström, T

    2004-01-01

    Particulate matter (PM) pollution adversely affects the airways, with asthmatic subjects thought to be especially sensitive. The authors hypothesised that exposure to diesel exhaust (DE), a major source of PM, would induce airway neutrophilia in healthy subjects, and that either these responses would be exaggerated in subjects with mild allergic asthma, or DE would exacerbate pre-existent allergic airways. Healthy and mild asthmatic subjects were exposed for 2 h to ambient levels of DE (particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) 108 microg x m(-3)) and lung function and airway inflammation were assessed. Both groups showed an increase in airway resistance of similar magnitude after DE exposure. Healthy subjects developed airway inflammation 6 h after DE exposure, with airways neutrophilia and lymphocytosis together with an increase in interleukin-8 (IL-8) protein in lavage fluid, increased IL-8 messenger ribonucleic acid expression in the bronchial mucosa and upregulation of the endothelial adhesion molecules. In asthmatic subjects, DE exposure did not induce a neutrophilic response or exacerbate their pre-existing eosinophilic airway inflammation. Epithelial staining for the cytokine IL-10 was increased after DE in the asthmatic group. Differential effects on the airways of healthy subjects and asthmatics of particles with a 50% cut-off aerodynamic diameter of 10 microm at concentrations below current World Health Organisation air quality standards have been observed in this study. Further work is required to elucidate the significance of these differential responses. PMID:14738236

  13. Relation of circulating T cell profiles to airway inflammation and asthma control in asthmatic pregnancy.

    PubMed

    Eszes, N; Bohács, A; Cseh, A; Toldi, G; Bikov, A; Ivancsó, I; Müller, V; Horváth, I; Rigó, J; Vásárhelyi, B; Losonczy, Gy; Tamási, L

    2012-09-01

    Asthmatic inflammation during pregnancy poses a risk for maternal and fetal morbidities. Circulating T cell immune phenotype is known to correlate with airway inflammation (detectable by fractional concentration of nitric oxide present in exhaled breath (FENO)) in non-pregnant allergic asthmatics. The aim of this study was to assess the relationship of peripheral T cell phenotype to FENO and clinical variables of asthma during pregnancy.We examined 22 pregnant women with allergic asthma in the 2nd/3rd trimester. The prevalence of Th1, Th2, regulatory T (Treg) and natural killer (NK) cell subsets was identified with flow cytometry using cell-specific markers. FENO, Asthma Control Test (ACT) total score and lung function were evaluated.Peripheral blood Th1, Th2, Treg, and NK cell prevalence were not significantly correlated to airway inflammation assessed by FENO in asthmatic pregnant women (all cells p > 0.05; study power > 75%). However, an inverse correlation was detected between Th2 cell prevalence and ACT total scores (p = 0.03) in asthmatic pregnancy.Blunted relationship between T cell profile and airway inflammation may be the result of pregnancy induced immune tolerance in asthmatic pregnancy. On the other hand, increased Th2 response impairs disease control that supports direct relationship between symptoms and cellular mechanisms of asthma during pregnancy. PMID:22982718

  14. A survey of daily asthmatic activity patterns in Cincinnati. Final report

    SciTech Connect

    Not Available

    1992-11-01

    A survey was undertaken in Cincinnati to obtain information on the activity patterns of asthmatics. Because studies have demonstrated symptomatic responses to elevated levels of SO{sub 2} only during outdoor exercise, information on the behavioral patterns of asthmatics is vital for the accurate estimation of risk due to air pollution exposures. In particular, data detailing the actual likelihood of asthmatics being engaged in strenuous outdoor activity at any given time of day is essential for an accurate appraisal of response probability. This, in turn, is necessary for an accurate estimate of risk. In the absence of such activity data, those concerned with the setting of short-term SO{sub 2} regulations are required to use purely subjective judgment to estimate how many asthmatics are engaged in strenuous outdoor exercise when SO{sub 2} levels are high enough to affect them. The activity pattern data give an indication of how much such an assumption would overestimate the true response and thus the true risk associated with SO{sub 2}. Lack of information on the activity patterns of asthmatics has thus been a critical gap in the SO{sub 2} risk assessment process. The primary purpose of this survey was to fill that gap.

  15. Effect of inhaled H1 and H2 receptor antagonist in normal and asthmatic subjects.

    PubMed Central

    Thomson, N C; Kerr, J W

    1980-01-01

    The effects on airflow resistance of an inhaled H1 receptor antagonist, clemastine, and an H2 receptor antagonist, cimetidine, have been investigated in normal and asthmatic subjects. No significant changes in specific conductance (sGaw) were seen in six normal subjects. In eight asthmatic subjects a significant increase in forced expiratory volume in one second (FEV1) occurred at 60 min (< 0.02), and 120 (< 0.05) after the inhalation of clemastine, whereas inhaled cimetidine had no effect on airflow resistance. Clemastine and cimetidine were tested on histamine-induced bronchoconstriction in eight normal and eight asthmatic subjects. Clemastine significantly reduced the fall in sGaw in normal subjects and the fall in FEV1 in asthmatic subjects, whereas cimetidine had no protective effect. Clemastine and ipratropium bromide were tested on methacholine-induced bronchoconstriction in eight normal subjects. Ipratropium bromide, but not clemastine, significantly reduced the fall in sGaw after methacholine. These results suggest that in normal and asthmatic subjects histamine-induced bronchoconstriction is mediated predominantly via H1 rather than H2 receptors in the airways. PMID:6449094

  16. Anti-tissue transglutaminase antibodies from coeliac patients inhibit transglutaminase activity both in vitro and in situ

    PubMed Central

    Esposito, C; Paparo, F; Caputo, I; Rossi, M; Maglio, M; Sblattero, D; Not, T; Porta, R; Auricchio, S; Marzari, R; Troncone, R

    2002-01-01

    Background and aims: Coeliac disease (CD) is a multifactorial disorder which has an autoimmune component characterised by the occurrence of disease specific autoreactive antibodies against the enzyme tissue transglutaminase (tTG). The aim of this study was to investigate whether binding of antibodies to the enzyme influences tTG activity. Methods: tTG activity was assayed in the presence of immunoglobulin A (IgA) and immunoglobulin G (IgG) purified from the serum of coeliac patients, CUB 7402 (an anti-tTG mouse monoclonal antibody), and human anti-tTG monoclonal antibodies derived from both intestinal lymphocytes from three patients with CD and from peripheral blood lymphocytes from healthy subjects. For our studies we used calcium treated and untreated recombinant human tTG. Furthermore, the effects of antibodies were determined by immunohistochemical detection of tTG activity in sections of human umbilical cord. Results: IgG and IgA from CD patients inhibited tTG activity in vitro in a dose dependent manner, with a different rate of inhibition among patients. The monoclonal antibody CUB 7402 and human monoclonal antibodies displayed a dose dependent inhibitory effect towards the catalytic activity of the enzyme, both in vitro and in situ. Preincubation of tTG with CaCl2 caused loss of the inhibitory effect due to CUB 7402 but not that caused by human monoclonal antibodies. Conclusions: Purified CD IgA, IgG, as well as human anti-tTG monoclonal antibodies inhibited the enzymatic activity of human tTG both in vitro and in situ. PMID:12117875

  17. Improved leucocyte migration inhibition response of leucocytes from lepromatous leprosy patients with hapten modified M. leprae.

    PubMed Central

    Fotedar, A; Mustafa, A S; Narang, B S; Talwar, G P

    1982-01-01

    Two acetoacetylated derivatives of Mycobacterium leprae with variable hapten groups and a conjugate with tetanus toxoid were prepared. These were tested as antigens along with unmodified M. leprae in the leucocyte migration inhibition response of leucocytes from clinically, bacteriologically and histopathologically confirmed cases of lepromatous leprosy. LMI response was poor with M. leprae, but was significantly enhanced with acetoacetylated M. leprae. PMID:6751637

  18. Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma.

    PubMed

    Rangwala, Reshma; Chang, Yunyoung C; Hu, Janice; Algazy, Kenneth M; Evans, Tracey L; Fecher, Leslie A; Schuchter, Lynn M; Torigian, Drew A; Panosian, Jeffrey T; Troxel, Andrea B; Tan, Kay-See; Heitjan, Daniel F; DeMichele, Angela M; Vaughn, David J; Redlinger, Maryann; Alavi, Abass; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; O'Dwyer, Peter J; Amaravadi, Ravi K

    2014-08-01

    The combination of temsirolimus (TEM), an MTOR inhibitor, and hydroxychloroquine (HCQ), an autophagy inhibitor, augments cell death in preclinical models. This phase 1 dose-escalation study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with TEM in cancer patients. In the dose escalation portion, 27 patients with advanced solid malignancies were enrolled, followed by a cohort expansion at the top dose level in 12 patients with metastatic melanoma. The combination of HCQ and TEM was well tolerated, and grade 3 or 4 toxicity was limited to anorexia (7%), fatigue (7%), and nausea (7%). An MTD was not reached for HCQ, and the recommended phase II dose was HCQ 600 mg twice daily in combination with TEM 25 mg weekly. Other common grade 1 or 2 toxicities included fatigue, anorexia, nausea, stomatitis, rash, and weight loss. No responses were observed; however, 14/21 (67%) patients in the dose escalation and 14/19 (74%) patients with melanoma achieved stable disease. The median progression-free survival in 13 melanoma patients treated with HCQ 1200mg/d in combination with TEM was 3.5 mo. Novel 18-fluorodeoxyglucose positron emission tomography (FDG-PET) measurements predicted clinical outcome and provided further evidence that the addition of HCQ to TEM produced metabolic stress on tumors in patients that experienced clinical benefit. Pharmacodynamic evidence of autophagy inhibition was evident in serial PBMC and tumor biopsies only in patients treated with 1200 mg daily HCQ. This study indicates that TEM and HCQ is safe and tolerable, modulates autophagy in patients, and has significant antitumor activity. Further studies combining MTOR and autophagy inhibitors in cancer patients are warranted. PMID:24991838

  19. Impaired Prepulse Inhibition and Prepulse-Elicited Reactivity but Intact Reflex Circuit Excitability in Unmedicated Schizophrenia Patients: a Comparison With Healthy Subjects and Medicated Schizophrenia Patients

    PubMed Central

    Csomor, Philipp A.; Yee, Benjamin K.; Feldon, Joram; Theodoridou, Anastasia; Studerus, Erich; Vollenweider, Franz X.

    2009-01-01

    Deficient sensorimotor gating as indexed by prepulse inhibition (PPI) of the startle response has been reported repeatedly in patients suffering from schizophrenia. According to the widely accepted “protective hypothesis,” PPI reflects the protection of ongoing information processing against interference by other stimuli. Alternatively, it has been proposed that PPI might be regulated by startle reflex circuit excitability. In the present study, we evaluated these 2 conceptually divergent approaches underlying the regulation of PPI. To this end, we assessed sensorimotor gating as indexed by PPI, the reactivity to the prepulse-alone stimulus indexed as prepulse-elicited reactivity (PPER), and acoustic blink reflex excitability in terms of paired pulse suppression (PPS) within a single recording session in 13 unmedicated and 24 medicated (11 first break) schizophrenia patients in comparison to 43 healthy control subjects. The results showed that PPI was significantly reduced in unmedicated, but not in medicated schizophrenia patients. Furthermore, unmedicated patients could be distinguished from the medicated patients and control subjects in terms of PPER. In contrast to PPI, PPS did not differ between patients and control subjects. These findings are in line with the “protective hypothesis” of PPI and indicate that reduced sensorimotor gating in schizophrenia patients might be based on a reduced perception and/or processing of the prepulse stimulus. The extent to which PPER may or may not be causally associated with sensorimotor gating in schizophrenia has to be further investigated in human and animal studies. PMID:18245063

  20. CONCENTRATIONS OF PARTICULATE ORGANIC SPECIES MEASURED IN INDOOR AND OUTDOOR ENVIRONMENTS DURING THE TAMPA ASTHMATIC CHILDREN'S STUDY ( TACS )

    EPA Science Inventory

    The Tampa Asthmatic Children's Study (TACS) was completed to assess environmental exposures for a group of asthmatic children (n = 9) under the age of six and living in Tampa, Florida. Concentrations of particulate organic species are reported from residential indoor, residential...

  1. Patient-derived xenografts of triple-negative breast cancer reproduce molecular features of patient tumors and respond to mTOR inhibition

    PubMed Central

    2014-01-01

    Introduction Triple-negative breast cancer (TNBC) is aggressive and lacks targeted therapies. Phosphatidylinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways are frequently activated in TNBC patient tumors at the genome, gene expression and protein levels, and mTOR inhibitors have been shown to inhibit growth in TNBC cell lines. We describe a panel of patient-derived xenografts representing multiple TNBC subtypes and use them to test preclinical drug efficacy of two mTOR inhibitors, sirolimus (rapamycin) and temsirolimus (CCI-779). Methods We generated a panel of seven patient-derived orthotopic xenografts from six primary TNBC tumors and one metastasis. Patient tumors and corresponding xenografts were compared by histology, immunohistochemistry, array comparative genomic hybridization (aCGH) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) sequencing; TNBC subtypes were determined. Using a previously published logistic regression approach, we generated a rapamycin response signature from Connectivity Map gene expression data and used it to predict rapamycin sensitivity in 1,401 human breast cancers of different intrinsic subtypes, prompting in vivo testing of mTOR inhibitors and doxorubicin in our TNBC xenografts. Results Patient-derived xenografts recapitulated histology, biomarker expression and global genomic features of patient tumors. Two primary tumors had PIK3CA coding mutations, and five of six primary tumors showed flanking intron single nucleotide polymorphisms (SNPs) with conservation of sequence variations between primary tumors and xenografts, even on subsequent xenograft passages. Gene expression profiling showed that our models represent at least four of six TNBC subtypes. The rapamycin response signature predicted sensitivity for 94% of basal-like breast cancers in a large dataset. Drug testing of mTOR inhibitors in our xenografts showed 77 to 99% growth inhibition, significantly more than

  2. Why do asthmatic subjects respond so strongly to inhaled adenosine?

    PubMed

    Meade, C J; Dumont, I; Worrall, L

    2001-08-01

    Bronchospasm induced by adenosine is blocked by representatives of all the major classes of drugs used in the treatment of asthma. Understanding the mechanism of this bronchospasm may help understand the way these drugs work. Clinical studies have suggested involvement of neural pathways, mast-like cells and mediators such as histamine, serotonin and lipoxygenase products. There is a strong link between responsiveness to adenosine and eosinophilia. In different animal models A1, A2b and A3 adenosine receptor subclasses have all been implicated in inducing bronchospasm. whilst occupation of the A2a receptor generally has no, or the opposite effect. At least two different mechanisms, both involving neural pathways, exist. One, involving the adenosine A1 receptor, functions in mast cell depleted animals; the other requires interaction with a population of mast-like cells activated over A2b or A3 receptors. Not only histamine but also serotonin and lipoxygenase products released from the mast-like cells are potential mediators. In animal models good reactivity to adenosine receptor agonists is generally only found when the animals are first sensitized and exposed to allergen in ways likely to induce an allergic inflammation. An exception is the BDE rat, which reacts to adenosine receptor agonists such as APNEA or NECA even without allergen exposure. This rat strain does however show evidence of spontaneous eosinophilic inflammation in the lung even without immunization. As mast cells both release adenosine and respond to adenosine, adenosine provides a non-specific method of amplifying specific signals resulting from IgE/antigen interaction. This mechanism may not only have a pathological significance in asthma; it may be part of a normal bodily defense response that in asthmatic subjects is inappropriately activated. PMID:11521747

  3. Platelet inhibition with prasugrel (CS‐747) compared with clopidogrel in patients undergoing coronary stenting: the subset from the JUMBO study

    PubMed Central

    Serebruany, V L; Midei, M G; Meilman, H; Malinin, A I; Lowry, D R

    2006-01-01

    Background Based on the preclinical and phase 1 studies, prasugrel, a novel platelet ADP P2Y12 receptor blocker, may be a more potent platelet inhibitor than clopidogrel. This study compared the antiplatelet properties of prasugrel in a small subset of patients enrolled in the JUMBO trial, and compared with historic clopidogrel treated controls. Methods and results Nine patients undergoing coronary stenting were randomised to one of three arms of prasugrel (40 mg loading, and 7.5 mg maintenance, n = 1; 60/10 mg, n = 4; or 60/15 mg, n = 2), or clopidogrel (300/75 mg, n = 2). Aspirin and GP IIb/IIIa inhibitors were permitted. Platelet activity was assessed at baseline, at 4, and 24 hours, and at 30 days after stent implantation in substudy participants, and compared with 124 historic controls who received clopidogrel. Independent of the loading, or maintenance dose, patients treated with prasugrel exhibited significantly more potent platelet inhibition as determined by ADP, and collagen induced aggregation, Ultegra Analyser, and surface expression of PECAM‐1, GPIIb/IIIa antigen, and activity with PAC‐1 antibody, GPIb, P‐selectin, CD40‐ligand, GP37, and thrombospondin receptor expression when compared with those treated with clopidogrel. There were no differences between antiplatelet agents with regard to vitronectin, LAMP‐1, PAR‐1 (intact and cleaved epitopes) thrombin receptor expression, or formation of platelet‐monocyte microparticles. Expression of GPIIb antigen, vitronectin, and LAMP‐3 receptor were not affected by both agents. Two patients treated with prasugrel 10 mg/daily exhibited complete inhibition of collagen induced aggregation at 30 days. Conclusion At the dosing regimens chosen in the JUMBO trial, it seems that prasugrel is a more potent antiplatelet agent than clopidogrel. Two episodes of profound platelet inhibition, which are not seen with clopidogrel, raise the possibility of higher bleeding risks

  4. Impaired inhibition of prepotent motor actions in patients with Tourette syndrome

    PubMed Central

    Wylie, Scott A.; Claassen, Daniel O.; Kanoff, Kristen E.; Ridderinkhof, K. Richard; van den Wildenberg, Wery P.M.

    2013-01-01

    Background Evidence that tic behaviour in individuals with Tourette syndrome reflects difficulties inhibiting prepotent motor actions is mixed. Response conflict tasks produce sensitive measures of response interference from prepotent motor impulses and the proficiency of inhibiting these impulses as an act of cognitive control. We tested the hypothesis that individuals with Tourette syndrome show a deficit in inhibiting prepotent motor actions. Methods Healthy controls and older adolescents/adults with persistent Tourette syndrome without a history of obsessive–compulsive disorder or attention-deficit/hyperactivity disorder and presenting with stable mood functioning (i.e., no history of well-treated anxiety or depression) participated in this study. They performed a Simon task that induced conflict between prepotent actions and goal-directed actions. A novel theoretical framework distinguished group differences in acting impulsively (i.e., fast motor errors) from the proficiency of inhibiting interference by prepotent actions (i.e., slope of interference reduction). Results We included 27 controls and 28 individuals with Tourette syndrome in our study. Both groups showed similar susceptibility to making fast, impulsive motor errors (Tourette syndrome 26% v. control 23%; p = 0.10). The slope (m) reduction of the interference effect was significantly less pronounced among participants with Tourette syndrome than controls (Tourette syndrome: m = −0.07 v. control: m = −0.23; p = 0.022), consistent with deficient inhibitory control over prepotent actions in Tourette syndrome. Limitations This study does not address directly the role of psychiatric comorbidities and medication effects on inhibitory control over impulsive actions in individuals with Tourette syndrome. Conclusion The results offer empirical evidence for deficient inhibitory control over prepotent motor actions in individuals with persistent Tourette syndrome with minimal to absent psychiatric

  5. The Effect of Aromatase Inhibition on the Cognitive Function of Older Patients with Breast Cancer

    PubMed Central

    Hurria, Arti; Patel, Sunita K.; Mortimer, Joanne; Luu, Thehang; Somlo, George; Katheria, Vani; Ramani, Rupal; Hansen, Kurt; Feng, Tao; Chuang, Carolyn; Geist, Cheri L.; Silverman, Daniel H.S.

    2014-01-01

    Purpose To evaluate the association between aromatase inhibitor (AI) therapy and cognitive function (over a 6-month time period) in a cohort of patients age ≥ 60 compared with an age-matched healthy control group, and to evaluate changes in regional cerebral metabolism as measured by positron emission tomography (PET) scans of the brain done in a subset of the patient cohort. Patients and Methods Thirty-five patients (32 evaluable) and 35 healthy controls were recruited to this study. Patients with breast cancer completed a neuropsychological battery, self-reported memory questionnaire, and geriatric assessment prior to initiation of AI therapy and again 6 months later. Age-matched healthy control participants completed the same assessments at the same time points as the patient group. Results No significant decline in cognitive function was seen among individuals receiving an AI from pre-treatment to 6 months later compared with healthy controls. In the PET cohort over the same period, both standardized volume of interest (sVOI) and statistical parametric mapping (SPM) analyses detected specific changes in metabolic activity between baseline and follow-up uniquely in the AI patients, uniquely, most significantly in medial temporal lobes. Conclusion While patients undergoing AI treatment demonstrated few changes in neuropsychologic performance compared with healthy controls over a 6-month period during this interval, regionally specific changes in cerebral metabolic activity were identified in the patient group. Additional longitudinal follow-up is needed to understand the potential clinical implications of these findings. PMID:24291380

  6. Modified expression of peripheral blood lymphocyte muscarinic cholinergic receptors in asthmatic children.

    PubMed

    Cherubini, Emanuela; Tabbì, Luca; Scozzi, Davide; Mariotta, Salvatore; Galli, Elena; Carello, Rossella; Avitabile, Simona; Tayebati, Seyed Koshrow; Amenta, Francesco; De Vitis, Claudia; Mancini, Rita; Ricci, Alberto

    2015-07-15

    Lymphocytes possess an independent cholinergic system. We assessed the expression of muscarinic cholinergic receptors in lymphocytes from 49 asthmatic children and 10 age matched controls using Western blot. We demonstrated that CD4+ and CD8+ T cells expressed M2 and M4 muscarinic receptors which density were significantly increased in asthmatic children in comparison with controls. M2 and M4 receptor increase was strictly related with IgE and fraction of exhaled nitric oxide (FeNO) measurements and with impairment in objective measurements of airway obstruction. Increased lymphocyte muscarinic cholinergic receptor expression may concur with lung cholinergic dysfunction and with inflammatory molecular framework in asthma. PMID:26025056

  7. Reversion of Asthmatic Complications and Mast Cell Signalling Pathways in BALB/c Mice Model Using Quercetin Nanocrystals.

    PubMed

    Gupta, Kriti; Kumar, Sandeep; Gupta, Rinkesh Kumar; Sharma, Akanksha; Verma, Alok K; Stalin, K; Chaudhari, Bhushan P; Das, Mukul; Singh, Surinder P; Dwivedi, Premendra D

    2016-04-01

    The tranquillizing effects of quercetin on allergic asthma are promising, but its poor water solubility and bioavailability is still a bottleneck. In this study, an ovalbumin (OVA) sensitized BALB/c mice asthma model was used to investigate the potential of quercetin nanocrystals (nQ) on relieving asthma aggravation. The water soluble nQ was prepared by the homogenization using the high energy sonication method. X-ray diffraction data showed the formation of nQ (10-30 nm) which was in agreement with transmission electron microscopy. The nQ was found to be more stable and soluble in PBS, and sera of BALB/c mice compared to bulk quercetin. Dose dependent experiments with nQ on OVA sensitized asthma mice exhibited significant anti-asthmatic potential of nQ at much lower dose (1 mg/kg body weight) compared to bulk quercetin. The treatment of nQ remarkably resulted in reduced OVA specific immunoglobulin E (sIgE) production, anaphylaxis signs and type 1 skin test. The nQ also significantly modulated the expression of Th2 cytokines like IL-4 and IL-5, which are responsible for IgE class switching and suppressed the degranulation/secretion of different chemical mediators (PGD2, mMCPT-1 Cys-L and TSLP) from activated mast cells. The levels of FcεR1, Syk, c-Yes, PI-3, p-PI-3, PLC-γ2, and p-PLC-γ2 were found to be reduced in the OVA sensitized BALB/c mice treated with nQ compared to those treated with OVA only. The results indicate that nQ alleviate pulmonary inflammation and airway hyporesponsiveness in allergic asthma at much lower dose compared to bulk quercetin and may be considered as a potential drug for the treatment of asthmatic patients. PMID:27301198

  8. Differential In Vitro Inhibition of Thrombin Generation by Anticoagulant Drugs in Plasma from Patients with Cirrhosis

    PubMed Central

    Potze, Wilma; Arshad, Freeha; Adelmeijer, Jelle; Blokzijl, Hans; van den Berg, Arie P.; Meijers, Joost C. M.; Porte, Robert J.; Lisman, Ton

    2014-01-01

    Background Treatment and prevention of thrombotic complications is frequently required in patients with cirrhosis. However anticoagulant therapy is often withheld from these patients, because of the perceived bleeding diathesis. As a result of the limited clinical experience, the anticoagulant of choice for the various indications is still not known. Objectives We evaluated the in vitro effect of clinically approved anticoagulant drugs in plasma from patients with cirrhosis. Patients/Methods Thirty patients with cirrhosis and thirty healthy controls were studied. Thrombin generation assays were performed before and after addition of unfractionated heparin, low molecular weight heparin, fondaparinux, dabigatran, and rivaroxaban, to estimate anticoagulant potencies of these drugs. Results Addition of dabigatran led to a much more pronounced reduction in endogenous thrombin potential in patients compared to controls (72.6% reduction in patients vs. 12.8% reduction in controls, P<0.0001). The enhanced effect of dabigatran was proportional to the severity of disease. In contrast, only a slightly increased anticoagulant response to heparin and low molecular weight heparin and even a reduced response to fondaparinux and rivaroxaban was observed in plasma from cirrhotic patients as compared to control plasma. Conclusions The anticoagulant potency of clinically approved drugs differs substantially between patients with cirrhosis and healthy individuals. Whereas dabigatran and, to a lesser extent, heparin and low molecular weight heparin are more potent in plasma from patients with cirrhosis, fondaparinux and rivaroxaban showed a decreased anticoagulant effect. These results may imply that in addition to dose adjustments based on altered pharmacokinetics, drug-specific dose adjustments based on altered anticoagulant potency may be required in patients with cirrhosis. PMID:24505487

  9. The influence of bilateral subthalamic nucleus deep brain stimulation on impulsivity and prepulse inhibition in Parkinson’s disease patients

    PubMed Central

    Gee, Lucy; Smith, Heather; Cruz, Priscilla De La; Campbell, Joannalee; Fama, Chris; Haller, Jessica; Ramirez-Zamora, Adolfo; Durphy, Jennifer; Hanspal, Era; Molho, Eric; Barba, Anne; Shin, Damian; Pilitsis, Julie G.

    2015-01-01

    Background At least 14% of Parkinson disease (PD) patients develop impulse control disorders (ICDs). The pathophysiology behind these behaviors and the impact of deep brain stimulation in a real-life setting remains unclear. Objectives We prospectively examined the impact of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on ICDs in PD patients, as well as the relationship between impaired sensorimotor gaiting and impulsivity. Methods Patients undergoing bilateral STN-DBS were assessed for ICDs preoperatively and 1-year postoperatively using a validated questionnaire (QUIP-RS). A subset of patients completed the Balloon Analog Risk Task (BART) and auditory pre-pulse inhibition (PPI) testing. Results Analysis revealed 12 patients had an improvement in score assessing ICDs (“good responders” – GR; p = 0.006) while 4 had a worse or stable score (“poor responders” – PR; p > 0.05). GR further exemplified a significant decrease in hypersexual behavior (p = 0.005) and binge eating (p = 0.01). Impaired PPI responses also significantly correlated with impulsivity in BART (r = −0.72, p = 0.044). Discussion Following bilateral STN-DBS 75% of our cohort had a reduction in ICDs, thus suggesting deep brain stimulation effectively manages ICDs in PD. The role of impaired PPI in predisposition to ICDs in PD warrants further investigation. PMID:26066569

  10. Factors Supporting and Inhibiting Adherence to HIV Medication Regimen in Women: A Qualitative Analysis of Patient Interviews

    PubMed Central

    Fagbami, Oluwakemi; Oluwasanjo, Adetokunbo; Fitzpatrick, Carrie; Fairchild, Rebecca; Shin, Ann; Donato, Anthony

    2015-01-01

    Adherence to antiretroviral therapy reduces morbidity and mortality; however rates of non-adherence are variable among women for unclear reasons. This study was a single-center qualitative analysis of interviews with 18 female HIV-positive non-adherent patients (defined by virologic failure) to explore psychosocial factors impacting adherence. Factors identified were categorized as promoting, inhibiting or having no effect on adherence. Three themes, characterized as social factors, illness factors and other societal pressures, were identified. Medical systems support, family support and compliance for children were most commonly identified as promoting adherence, while psychiatric comorbidities, lack of medical systems support and side effects were identified most often as inhibitors of adherence. While stigma was frequently identified, it was not seen as a barrier to adherence. Enhancing relationships between patients and their providers as well as their community support systems are critical avenues to pursue in improving compliance. Interventions to promote compliance are important avenues of future research. PMID:26157537

  11. Pseudomonas aeruginosa inhibits the growth of Scedosporium aurantiacum, an opportunistic fungal pathogen isolated from the lungs of cystic fibrosis patients

    PubMed Central

    Kaur, Jashanpreet; Pethani, Bhavin P.; Kumar, Sheemal; Kim, Minkyoung; Sunna, Anwar; Kautto, Liisa; Penesyan, Anahit; Paulsen, Ian T.; Nevalainen, Helena

    2015-01-01

    The filamentous fungus Scedosporium aurantiacum and the bacterium Pseudomonas aeruginosa are opportunistic pathogens isolated from lungs of the cystic fibrosis (CF) patients. P. aeruginosa has been known to suppress the growth of a number of CF related fungi such as Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans. However, the interactions between P. aeruginosa and S. aurantiacum have not been investigated in depth. Hence we assessed the effect of P. aeruginosa reference strain PAO1 and two clinical isolates PASS1 and PASS2 on the growth of two clinical S. aurantiacum isolates WM 06.482 and WM 08.202 using solid plate assays and liquid cultures, in a synthetic medium mimicking the nutrient condition in the CF sputum. Solid plate assays showed a clear inhibition of growth of both S. aurantiacum strains when cultured with P. aeruginosa strains PASS1 and PAO1. The inhibitory effect was confirmed by confocal microscopy. In addition to using chemical fluorescent stains, strains tagged with yfp (P. aeruginosa PASS1) and mCherry (S. aurantiacum WM 06.482) were created to facilitate detailed microscopic observations on strain interaction. To our knowledge, this is the first study describing successful genetic transformation of S. aurantiacum. Inhibition of growth was observed only in co-cultures of P. aeruginosa and S. aurantiacum; the cell fractions obtained from independent bacterial monocultures failed to initiate a response against the fungus. In the liquid co-cultures, biofilm forming P. aeruginosa strains PASS1 and PAO1 displayed higher inhibition of fungal growth when compared to PASS2. No change was observed in the inhibition pattern when direct cell contact between the bacterial and fungal strains was prevented using a separation membrane suggesting the involvement of extracellular metabolites in the fungal inhibition. However, one of the most commonly described bacterial virulence factors, pyocyanin, had no effect against either of the S

  12. Spirometric evaluation of pulmonary function tests in clinically diagnosed patients of bronchial asthma.

    PubMed

    Prajapati, R; Shrestha, B; Dhungel, S; Devkota, K C; Pramanik, T; Roychowdhury, P

    2010-03-01

    The present study was undertaken to assess the difference between the normal predicted value and observed value of pulmonary function test (PFT) amongst the asthmatic patients and also to compare the aforesaid observed values between male and female asthmatic patients. Clinically diagnosed cases (male 62, female 75) of bronchial asthma attending medical out patient department of Nepal Medical College Teaching Hospital were assessed. All the pulmonary parameters showed significantly less observed values than the normal predicted values except PEFR in female and FVC in male asthmatic patients. Hence, PEFR in female and FVC in male asthmatic patients might not be considered as a valid parameter to indicate bronchial asthma. Present study also revealed that all the pulmonary variables were significantly higher in males than in females. PMID:20677610

  13. Proteasomal Inhibition Restores Biological Function of Mis-sense Mutated Dysferlin in Patient-derived Muscle Cells*

    PubMed Central

    Azakir, Bilal A.; Di Fulvio, Sabrina; Kinter, Jochen; Sinnreich, Michael

    2012-01-01

    Dysferlin is a transmembrane protein implicated in surface membrane repair of muscle cells. Mutations in dysferlin cause the progressive muscular dystrophies Miyoshi myopathy, limb girdle muscular dystrophy 2B, and distal anterior compartment myopathy. Dysferlinopathies are inherited in an autosomal recessive manner, and many patients with this disease harbor mis-sense mutations in at least one of their two pathogenic DYSF alleles. These patients have significantly reduced or absent dysferlin levels in skeletal muscle, suggesting that dysferlin encoded by mis-sense alleles is rapidly degraded by the cellular quality control system. We reasoned that mis-sense mutated dysferlin, if salvaged from degradation, might be biologically functional. We used a dysferlin-deficient human myoblast culture harboring the common R555W mis-sense allele and a DYSF-null allele, as well as control human myoblast cultures harboring either two wild-type or two null alleles. We measured dysferlin protein and mRNA levels, resealing kinetics of laser-induced plasmalemmal wounds, myotube formation, and cellular viability after treatment of the human myoblast cultures with the proteasome inhibitors lactacystin or bortezomib (Velcade). We show that endogenous R555W mis-sense mutated dysferlin is degraded by the proteasomal system. Inhibition of the proteasome by lactacystin or Velcade increases the levels of R555W mis-sense mutated dysferlin. This salvaged protein is functional as it restores plasma membrane resealing in patient-derived myoblasts and reverses their deficit in myotube formation. Bortezomib and lactacystin did not cause cellular toxicity at the regimen used. Our results raise the possibility that inhibition of the degradation pathway of mis-sense mutated dysferlin could be used as a therapeutic strategy for patients harboring certain dysferlin mis-sense mutations. PMID:22318734

  14. Radiographic and Histopathologic Observations After Combined EGFR Inhibition and Hypofractionated Stereotactic Radiosurgery in Patients With Recurrent Malignant Gliomas

    SciTech Connect

    Schwer, Amanda L.; Kavanagh, Brian D.; McCammon, Robert; Gaspar, Laurie E.; Kleinschmidt-De Masters, B.K.; Stuhr, Kelly; Chen Changhu

    2009-04-01

    Purpose: To describe the radiographic and histopathologic changes after stereotactic radiosurgery (SRS) and epidermal growth factor receptor inhibition in patients with recurrent malignant gliomas. Methods and Materials: A total of 15 patients with recurrent high-grade gliomas were treated on a prospective Phase I trial combining SRS and gefitinib. The SRS dose was escalated from 18 to 36 Gy in three fractions. The planning target volume was the T{sub 1}-weighted contrast-enhancing (T{sub 1}C) lesion plus 2 mm. Gefitinib was given at 250 mg daily. Serial brain magnetic resonance imaging scans were analyzed to characterize the volumetric changes in the T{sub 1}C and T{sub 2} abnormalities after treatment. Two patients underwent resection for suspected recurrence. Results: The median pretreatment magnetic resonance imaging T{sub 1}C and T{sub 2} volume was 40.9 and 184.1 cm{sup 3}, respectively. The median post-SRS percentage of increases in the T{sub 1}C volume at 1, 2-4, and 5-7 months was 8.9%, 41.3%, and 99.6%, respectively. The median percentage increase in the T{sub 2} volume likewise showed a trend upward after SRS, from 18.0% at 1 month to 37.8% at 5-7 months. For the 2 patients who underwent resection after SRS for an increasing T{sub 1}C volume, the histopathologic analysis revealed therapy-induced vascular injury and necrosis. One patient with an asymptomatic increase in the T{sub 1}C volume after SRS was treated conservatively. After a peak T{sub 1}C volume increase at 9 months, the T{sub 1}C volume had declined to 50% of the maximal volume at 15 months. The patients with the most dramatic increase in T{sub 1}C volume experienced the longest overall survival. Conclusion: Patients experienced a notable increase in magnetic resonance imaging T{sub 1}C and T{sub 2} volumes after the combination of SRS and epidermal growth factor receptor inhibition. The tissue changes were consistent with a potent treatment effect.

  15. Preserved Transcallosal Inhibition to Transcranial Magnetic Stimulation in Nondemented Elderly Patients with Leukoaraiosis

    PubMed Central

    Bella, Rita; Giuffrida, Salvatore; Pennisi, Giovanni; Spampinato, Concetto; Giordano, Daniela; Malaguarnera, Giulia; Raggi, Alberto; Pennisi, Manuela

    2013-01-01

    Structural corpus callosum (CC) changes in patients with leukoaraiosis (LA) are significantly associated with cognitive and motor impairment. The aim of this study is to investigate the transcallosal fibers functioning by means of transcranial magnetic stimulation (TMS) in elderly patients with LA. The resting motor threshold (rMT), the motor-evoked potentials (MEPs), and the controlateral (cSP) and ipsilateral silent periods (iSP) were determined using single-pulse TMS in 15 patients and 15 age-matched controls. The neuropsychological profile and the vascular burden at brain magnetic resonance imaging (MRI) were concomitantly explored. Patients reported abnormal scores at tests evaluating executive control functions. No significant difference was found in TMS measures of intra- and intercortical excitability. No CC lesion was evident at MRI. Transcallosal inhibitory mechanisms to TMS seem to be spared in LA patients, a finding which is in line with neuroimaging features and suggests a functional integrity of the CC despite the ischemic interruption of corticosubcortical loops implicated in cognition and behavior. The observed neurophysiological finding differs from that reported in degenerative dementia, even in the preclinical or early stage. In our group of patients, the pure extent of LA is more related to impairment of frontal lobe abilities rather than functional callosal changes. PMID:23984349

  16. Pulmonary gas exchange during histamine-induced bronchoconstriction in asthmatic subjects.

    PubMed

    Burke, T V; Küng, M; Burki, N K

    1989-10-01

    Bronchial provocation for testing airway hyperreactivity is now well-established. However, the effects of histamine-induced bronchoconstriction on pulmonary gas exchange in man have not been systematically studied. We empirically noted marked decreases in PaO2 in some asthmatic subjects following induced bronchoconstriction. Nine subjects with mild, stable asthma were studied, each on two separate days. The first determined the dose of inhaled histamine necessary to decrease FEV1 by 20 percent and the relationship to lung volume and to pulmonary resistance by the interrupter technique (Rint). On the second day arterial blood gases, ventilation, Rint, and the anatomic (VDan) and physiologic (VDphys) dead spaces were measured simultaneously. There was a significant (p less than 0.05), profound fall in PaO2 (mean, -21.8 mm Hg) and in P(A-a)O2 (mean +14.7 mm Hg) within 5 min after bronchoconstriction, associated with a significant (p less than 0.05) increase in respiratory frequency (mean +5.1 min-1); and decrease in tidal volume (mean, -0.3 L). The ratio VDphys/VT increased significantly (p less than 0.05; mean change, +0.08) even though VDan and VDphys did not. Bronchoconstriction induced the broadening of ventilation (V)/perfusion (Q) ratios, with, most likely, an increase in areas of high V/Q. Histamine-induced bronchoconstriction in mild asthma results in a marked fall in PaO2 due to induced V/Q inequality. Therefore, histamine airway challenge should be used with caution in patients with any preexisting hypoxemia. PMID:2791669

  17. Respiratory Impairment and Systemic Inflammation in Cedar Asthmatics Removed from Exposure

    PubMed Central

    Carlsten, Chris; Dybuncio, Anne; Pui, Mandy M.; Chan-Yeung, Moira

    2013-01-01

    Background Prior research has shown that removing occupational asthmatics from exposure does not routinely lead to significant improvements in respiratory impairment. These studies were of limited duration and factors determining recovery remain obscure. Our objective was to evaluate residual respiratory impairment and associated sputum and blood biomarkers in subjects with Western red cedar asthma after exposure cessation. Methods Subjects previously diagnosed with cedar asthma, and removed from exposure to cedar dust for at least one year, were recruited. Subjects completed a questionnaire and spirometry. PC20 (methacholine concentration that produces 20% fall in FEV1 (forced expiratory volume at 1 second)) sputum cellularity and select Th1/Th2 (T helper cells 1 and 2) cytokine concentrations in peripheral blood were determined. The asthma impairment class was determined and multivariate analyses were performed to determine its relationship with sputum cell counts and serum cytokines. Results 40 non-smoking males (mean age 62) were examined at a mean interval of 25 years from cedar asthma diagnosis and 17 years from last cedar exposure. 40% were in impairment class 2/3. On average, the PC20 had increased by 2.0 mg/ml; the FEV1 decreased by 1.5 L, with greater decrease in those with greater impairment. Higher impairment was associated with serum interferon-gamma (mean = 1.3 pg/ml in class 2/3 versus 0.62 pg/ml in class 0/1, p = 0.04), mainly due to the FEV1 component (correlation with interferon-gamma = −0.46, p = 0.005). Conclusion Years after exposure cessation, patients with Western red cedar asthma have persistent airflow obstruction and respiratory impairment, associated with systemic inflammation. PMID:23468925

  18. Airway mucosal permeability in chronic bronchitics and bronchial asthmatics with hypersecretion

    SciTech Connect

    Honda, I.; Shimura, S.; Sasaki, T.; Sasaki, H.; Takishima, T.; Nakamura, M.

    1988-04-01

    To determine airway mucosal permeability, radiolabeled albumin in sputum was examined on the basis of a 2-h period of sputum collection for as long as 8h after intravenous administration of /sup 131/I-labeled human serum albumin. This technique was applied to 12 patients with bronchial asthma associated with hypersecretion or chronic bronchitis. Group A consisted of 6 asthmatics (2 females and 4 males, 56.0 +/- 6.4 yr of age, mean +/- SEM); Group B consisted of 6 bronchitics (3 females and 3 males, 53.8 +/- 6.5 yr of age). Between Groups A and B, there was no significant difference in sputum volume per day or in obstructive impairment. Radiolabeled albumin concentration (cpm/ml) was obtained from radiocount of each sputum sample and then divided by serum concentration at the time of each sampling (2, 4, 6, and 8 h after administration). Group B showed large values compared with those in Group A. In Group A, the ratios were 2.0 +/- 0.8, 2.5 +/- 0.5, 2.2 +/- 0.2, and 1.5 +/- 0.4% (mean +/- SEM) at 2, 4, 6, and 8 h after the administration, respectively, whereas in Group B, the ratios were 3.0 +/- 0.6, 7.0 +/- 1.8, 7.2 +/- 1.8, and 7.4 +/- 2.4%, respectively. The differences between Groups A and B were statistically significant (two-way analysis of variance). These findings suggest that an increase in airway mucosal permeability is due to mucosal epithelial damage by chronic inflammation in bronchitics and not to the underlying abnormality of asthma.

  19. Sputum RNA signature in allergic asthmatics following allergen bronchoprovocation test

    PubMed Central

    Zuiker, Rob G.J.A.; Tribouley, Catherine; Diamant, Zuzana; Boot, J. Diderik; Cohen, Adam F.; Van Dyck, K.; De Lepeleire, I.; Rivas, Veronica M.; Malkov, Vladislav A.; Burggraaf, Jacobus; Ruddy, Marcella K.

    2016-01-01

    with lung function and sputum eosinophil counts. Conclusion Our RNA extraction and profiling protocols allowed reproducible assessments of inflammatory signatures in sputum including quantification of drug effects on this response in allergic asthmatics. This approach offers novel possibilities for the development of pharmacodynamic (PD) biomarkers in asthma. PMID:27421833

  20. Effects of ultrafine particles on the allergic inflammation in the lung of asthmatics: results of a double-blinded randomized cross-over clinical pilot study

    PubMed Central

    2014-01-01

    Background Epidemiological and experimental studies suggest that exposure to ultrafine particles (UFP) might aggravate the allergic inflammation of the lung in asthmatics. Methods We exposed 12 allergic asthmatics in two subgroups in a double-blinded randomized cross-over design, first to freshly generated ultrafine carbon particles (64 μg/m3; 6.1 ± 0.4 × 105 particles/cm3 for 2 h) and then to filtered air or vice versa with a 28-day recovery period in-between. Eighteen hours after each exposure, grass pollen was instilled into a lung lobe via bronchoscopy. Another 24 hours later, inflammatory cells were collected by means of bronchoalveolar lavage (BAL). (Trial registration: NCT00527462) Results For the entire study group, inhalation of UFP by itself had no significant effect on the allergen induced inflammatory response measured with total cell count as compared to exposure with filtered air (p = 0.188). However, the subgroup of subjects, which inhaled UFP during the first exposure, exhibited a significant increase in total BAL cells (p = 0.021), eosinophils (p = 0.031) and monocytes (p = 0.013) after filtered air exposure and subsequent allergen challenge 28 days later. Additionally, the potential of BAL cells to generate oxidant radicals was significantly elevated at that time point. The subgroup that was exposed first to filtered air and 28 days later to UFP did not reveal differences between sessions. Conclusions Our data demonstrate that pre-allergen exposure to UFP had no acute effect on the allergic inflammation. However, the subgroup analysis lead to the speculation that inhaled UFP particles might have a long-term effect on the inflammatory course in asthmatic patients. This should be reconfirmed in further studies with an appropriate study design and sufficient number of subjects. PMID:25204642

  1. Omega-3 fatty acids inhibit the up-regulation of endothelial chemokines in maintenance hemodialysis patients

    PubMed Central

    Hung, Adriana M.; Booker, Cindy; Ellis, Charles D.; Siew, Edward D.; Graves, Amy J.; Shintani, Ayumi; Abumrad, Naji N.; Himmelfarb, Jonathan; Ikizler, Talat Alp

    2015-01-01

    Background Chronic systemic inflammation is common in patients with chronic kidney disease on dialysis (CKD5D) and has been considered a key mediator of the increased cardiovascular risk in this patient population. In this study, we tested the hypothesis that supplementation of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) will attenuate the systemic inflammatory process in CKD5D patients. Methods The design was a randomized, double-blinded, placebo controlled pilot trial (NCT00655525). Thirty-eight patients were randomly assigned in a 1 : 1 fashion to receive 2.9 g of eicosapentaenoic acid (C20:5, n-3) plus docosahexaenoic acid (C22:6, n-3) versus placebo for 12 weeks. The primary outcome was change in pro-inflammatory chemokines measured by lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Secondary outcomes were changes in systemic inflammatory markers. Analysis of covariance was used to compare percent change from baseline to 12 weeks. Results Thirty-one patients completed 12 weeks and three patients completed 6 weeks of the study. Median age was 52 (interquartile range 45, 60) years, 74% were African-American and 79% were male. Supplementation of ω-3 PUFAs effectively decreased the LPS-induced PBMC expression of RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted) and MCP-1 (Monocyte Chemotactic Protein-1; unadjusted P = 0.04 and 0.06; adjusted for demographics P = 0.02 and 0.05, respectively). There was no significant effect of the intervention on serum inflammatory markers (C-reactive protein, interleukin-6 and procalcitonin). Conclusions The results of this pilot study suggest that supplementation of ω-3 PUFAs is beneficial in decreasing the levels of endothelial chemokines, RANTES and MCP-1. Studies of larger sample size and longer duration are required to further evaluate effects of ω-3 PUFAs on systemic markers of inflammation, other metabolic parameters and clinical outcomes, particularly

  2. Impact of non-inhibited platelet supplementation on platelet reactivity in patients treated with prasugrel or ticagrelor for an acute coronary syndrome: An ex vivo study.

    PubMed

    Bonhomme, Fanny; Bonvini, Robert; Reny, Jean-Luc; Poncet, Antoine; Fontana, Pierre

    2015-01-01

    Managing bleeding in patients receiving P2Y12 inhibitors is challenging. Few data are available regarding the efficacy of platelet transfusion in patients treated with prasugrel or ticagrelor. The aim of this study was to evaluate the minimal amount of platelet supplementation (in terms of ratio of non-inhibited platelets to inhibited platelets) necessary to restore platelet reactivity in platelet-rich plasma (PRP) of patients treated with aspirin and a prasugrel or ticagrelor loading dose for an acute coronary syndrome. PRP samples from patients were mixed ex vivo with increasing proportions of pooled PRP from healthy volunteers. Platelet reactivity was challenged with adenosine diphosphate (ADP), arachidonic acid, collagen or thrombin receptor activating peptide using light transmission aggregometry. The primary endpoint was the proportion of patient samples recovering an ADP-induced maximal aggregation (ADP-Aggmax) value above 40%. In patients treated with prasugrel (n = 32), ADP-Aggmax increased progressively with supplements of pooled PRP, with an average increase of 7.9% (95% CI [7.1; 8.8], p < 0.001) per each 20% increase in the ratio of non-inhibited platelets to inhibited platelets. A ratio of 60% was associated with 90% of patients reaching the primary endpoint. In patients treated with ticagrelor (n = 15), ADP-Aggmax did not significantly increase with any level of supplements. In conclusions, ex vivo addition of non-inhibited platelets significantly improved ADP-Aggmax in patients treated with prasugrel with a dose-dependent effect. There was no evidence of such a reversal in patients treated with ticagrelor. These results suggest that platelet transfusion may be more effective in blunting bleeding in patients treated with prasugrel, than those treated with ticagrelor. PMID:25905916

  3. PI3Kδ Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma

    PubMed Central

    Gopal, Ajay K.; Kahl, Brad S.; de Vos, Sven; Wagner-Johnston, Nina D.; Schuster, Stephen J.; Jurczak, Wojciech J.; Flinn, Ian W.; Flowers, Christopher R.; Martin, Peter; Viardot, Andreas; Blum, Kristie A.; Goy, Andre H.; Davies, Andrew J.; Zinzani, Pier Luigi; Dreyling, Martin; Johnson, Dave; Miller, Langdon L.; Holes, Leanne; Li, Daniel; Dansey, Roger D.; Godfrey, Wayne R.; Salles, Gilles A.

    2014-01-01

    Background Phosphatidylinositol-3-kinase delta (PI3Kδ) mediates B-cell receptor signaling and microenvironmental support signals that promote the growth and survival of malignant B lymphocytes. In a phase 1 study, idelalisib, an orally active selective PI3Kδ inhibitor, showed antitumor activity in patients with previously treated indolent non-Hodgkin's lymphomas. Methods In this single-group, open-label, phase 2 study, 125 patients with indolent non-Hodgkin's lymphomas who had not had a response to rituximab and an alkylating agent or had had a relapse within 6 months after receipt of those therapies were administered idelalisib, 150 mg twice daily, until the disease progressed or the patient withdrew from the study. The primary end point was the overall rate of response; secondary end points included the duration of response, progression-free survival, and safety. Results The median age of the patients was 64 years (range, 33 to 87); patients had received a median of four prior therapies (range, 2 to 12). Subtypes of indolent non-Hodgkin's lymphoma included follicular lymphoma (72 patients), small lymphocytic lymphoma (28), marginal-zone lymphoma (15), and lymphoplasmacytic lymphoma with or without Waldenström's macroglobulinemia (10). The response rate was 57% (71 of 125 patients), with 6% meeting the criteria for a complete response. The median time to a response was 1.9 months, the median duration of response was 12.5 months, and the median progression-free survival was 11 months. Similar response rates were observed across all subtypes of indolent non-Hodgkin's lymphoma, though the numbers were small for some categories. The most common adverse events of grade 3 or higher were neutropenia (in 27% of the patients), elevations in aminotransferase levels (in 13%), diarrhea (in 13%), and pneumonia (in 7%). Conclusions In this single-group study, idelalisib showed antitumor activity with an acceptable safety profile in patients with indolent non

  4. Maintenance of parasympathetic inhibition following emotional induction in patients with restrictive type anorexia nervosa.

    PubMed

    Rommel, Delphine; Nandrino, Jean-Louis; De Jonckheere, Julien; Swierczek, Marie; Dodin, Vincent; Logier, Régis

    2015-02-28

    This study aimed to explore changes in heart rate variability (HRV), a proxy for parasympathetic activity characterizing emotion regulation processes before, during and after negative emotional induction in patients suffering from restrictive type anorexia nervosa (AN-RT). We compared two methods of HRV analysis, the Fast Fourier Transform high frequency (FFT-HF) and a specific HRV high frequency analysis technique, namely, the wavelet transform HRV (WT-HRV). A sample of 16 inpatients with AN-RT was compared to 24 control participants. Heart rate (HR) was continuously recorded for 5 min before the beginning of the video until 5 min after the video. The participants answered questionnaires concerning their eating behaviors, mood disorders and difficulties in emotion regulation. During the entire procedure, the FFT-HF in patients was lower than that in controls. Using the WT-HRV, the patients did not differ from the controls at baseline, and only the controls showed a decrease during emotional induction. After the video, the WT-HRV in patients began to decrease during the first 2 min of emotional recovery although the WT-HRV in controls was already increased. These results highlighted the disturbances in the physiological dynamics of emotion regulation processes in patients with AN-RT. PMID:25500345

  5. Qualitative Study of the Use of Traditional Healing by Asthmatic Navajo Families

    ERIC Educational Resources Information Center

    Van Sickle, David; Morgan, Frank; Wright, Anne L.

    2003-01-01

    Despite increasing prevalence of asthma among American Indians and/or Alaska Natives, little is known about their use of traditional healing in its management. A convenience sample of 24 Navajo families with asthmatic members (n=35) was interviewed between June 1997 and September 1998. While 46% of families had previously used traditional healing,…

  6. AMBIENT COARSE PARTICULATE MATTER ASSOCIATED WITH PLASMINOGEN AND FIBRIOGEN LEVELS IN ADULT ASTHMATICS

    EPA Science Inventory

    Introduction: Recent reports indicate that the elderly and those with cardiovascular disease are susceptible to fine and coarse particulate matter (PM 2.5, PM 2.5-10) exposures. Asthmatics are thought to be primarily affected via airway inflammation. We investigated whether mark...

  7. An Analysis of the Hyperactive Syndrome: A Comparison of Hyperactive, Behavior Problem, Asthmatic and Normal Children.

    ERIC Educational Resources Information Center

    Firestone, Philip; Martin, Jaclynn E.

    This study attempted to identify cognitive and behavioral deficits which might be unique to hyperactive children. Fifty children between the ages of 5 and 12 were subjects of the investigation. Four experimental groups were formed: Hyperactive (HA), Behavior Problem Children (BP), Severely Asthmatic Children (AC), and Normal Control Children (NC).…

  8. CONTROLLED EXPOSURES OF HEALTHY AND ASTHMATIC VOLUNTEERS TO CONCENTRATED AMBIENT PARTICLES IN METROPOLITAN LOS ANGELES

    EPA Science Inventory

    Investigators expect to use a Harvard ambient particle concentrator to assess the effects of exposure to concentrated ambient particles (CAPs) on healthy and asthmatic people.  12 healthy individuals and 12 individuals with mild asthma will be exposed to either filtere...

  9. ANTIOXIDANT SUPPLEMENTATION AND LUNG FUNCTIONS AMONG ASTHMATIC CHILDREN EXPOSED TO HIGH LEVELS OF AIR POLLUTANTS

    EPA Science Inventory

    Abstract

    Air pollutant exposure has been related to adverse respiratory effects, in particular, in asthmatics. This effect could be the consequence of the oxidative stress caused by air pollutants on the lung. Antioxidant vitamins are free- radical scavengers, and could ha...

  10. QUANTITATIVE PCR ANALYSIS OF MOLDS IN THE DUST FROM HOMES OF ASTHMATIC CHILDREN IN NORTH CAROLINA

    EPA Science Inventory

    The vacuum bag (VB) dust was analyzed by mold specific quantitative PCR. These results were compared to the analysis survey calculated for each of the homes. The mean and standard deviation (SD) of the ERMI values in the homes of the NC asthmatic children was 16.4 (6.77), compa...

  11. Hookah Smoking and Harm Perception among Asthmatic Adolescents: Findings from the Florida Youth Tobacco Survey

    ERIC Educational Resources Information Center

    Martinasek, Mary P.; Gibson-Young, Linda; Forrest, Jamie

    2014-01-01

    Background: Hookah tobacco smoking has increased in prevalence among Florida adolescents and is often viewed as a safer alternative to cigarette smoking by young adults. Asthmatic adolescents are at increased risk of the negative health effects of hookah smoking. The purpose of this study is to examine if hookah use and harm perception vary by…

  12. HIGHER ENVIRONMENTAL RELATIVE MOLDINESS INDEX (ERMISM) VALUES MEASURED IN DETROIT HOMES OF SEVERELY ASTHMATIC CHILDREN

    EPA Science Inventory

    Sieved vacuum bag dust from the homes of 143 children in Detroit was analyzed by mold specific quantitative PCR (MSQPCR) and the Environmental Relative Moldiness Index (ERMIsm) was calculated for each home. Children living in these homes were categorized into non-asthmatic (n=8...

  13. Correlations of Flow Structure and Particle Deposition with Structural Alterations in Severe Asthmatic Lungs

    NASA Astrophysics Data System (ADS)

    Choi, Sanghun; Miyawaki, Shinjiro; Choi, Jiwoong; Hoffman, Eric A.; Wenzel, Sally; Lin, Ching-Long

    2014-11-01

    Severe asthmatics are characterized by alterations of bifurcation angle, hydraulic diameter, circularity of the airways, and local shift of air-volume functional change. The characteristics altered against healthy human subjects can affect flow structure and particle deposition. A large-eddy-simulation (LES) model for transitional and turbulent flows is utilized to study flow characteristics and particle deposition with representative healthy and severe asthmatic lungs. For the subject-specific boundary condition, local air-volume changes are derived with two computed tomography images at inspiration and expiration. Particle transport simulations are performed on LES-predicted flow fields. In severe asthmatics, the elevated air-volume changes of apical lung regions affect the increased particle distribution toward upper lobes, especially for small particles. The constricted airways are significantly correlated with high wall shear stress, leading to the increased pressure drop and particle deposition. The structural alterations of bifurcation angle, circularity and hydraulic diameter in severe asthmatics are associated with the increase of particle deposition, wall shear stress and wall thickness. NIH Grants: U01-HL114494, R01-HL094315 and S10-RR022421. Computer time: XSEDE.

  14. AMBIENT COARSE PARTICLE MATTER ASSOCIATED WITH HRV, BLOOD COAGULATION, AND BLOOD LIPIDS IN ADULT ASTHMATICS

    EPA Science Inventory

    Introduction: We investigated whether systemic inflammation markers in asthmatics change in response to fluctuations in ambient PM. Methods: Twelve atopic adults with mild to moderate persistent asthma living within a 30 mile radius of the US EPA clinic were followed for twelve w...

  15. Effect of inhaled dust mite allergen on regional particle deposition and mucociliary clearance in allergic asthmatics**

    EPA Science Inventory

    Background Acute exacerbations in allergic asthmatics may lead to impaired ability to clear mucus from the airways, a key factor in asthma morbidity. Objective The purpose of this study was to determine the effect of inhaled house dust mite challenge on the regional deposition of...

  16. Do inhaled beta(2)-agonists have an ergogenic potential in non-asthmatic competitive athletes?

    PubMed

    Kindermann, Wilfried

    2007-01-01

    The prevalence of asthma is higher in elite athletes than in the general population. The risk of developing asthmatic symptoms is the highest in endurance athletes and swimmers. Asthma seems particularly widespread in winter-sport athletes such as cross-country skiers. Asthmatic athletes commonly use inhaled beta(2)-agonists to prevent and treat asthmatic symptoms. However, beta(2)-agonists are prohibited according to the Prohibited List of the World Anti-Doping Agency. An exception can be made only for the substances formoterol, salbutamol, salmeterol and terbutaline by inhalation, as long as a therapeutic use exemption has been applied for and granted. In this context, the question arises of whether beta(2)-agonists have ergogenic benefits justifying the prohibition of these substances. In 17 of 19 randomised placebo-controlled trials in non-asthmatic competitive athletes, performance-enhancing effects of the inhaled beta(2)-agonists formoterol, salbutamol, salmeterol and terbutaline could not be proved. This is particularly true for endurance performance, anaerobic power and strength performance. In three of four studies, even supratherapeutic doses of salbutamol (800-1200 microg) had no ergogenic effect. In contrast to inhaled beta(2)-agonists, oral administration of salbutamol seems to be able to improve the muscle strength and the endurance performance. There appears to be no justification to prohibit inhaled beta(2)-agonists from the point of view of the ergogenic effects. PMID:17241101

  17. Oximetry Signal Processing Identifies REM Sleep-Related Vulnerability Trait in Asthmatic Children

    PubMed Central

    Perez, Geovanny F.; Gutierrez, Maria J.; Huseni, Shehlanoor; Pancham, Khrisna; Rodriguez-Martinez, Carlos E.; Nino, Cesar L.; Nino, Gustavo

    2013-01-01

    Rationale. The sleep-related factors that modulate the nocturnal worsening of asthma in children are poorly understood. This study addressed the hypothesis that asthmatic children have a REM sleep-related vulnerability trait that is independent of OSA. Methods. We conducted a retrospective cross-sectional analysis of pulse-oximetry signals obtained during REM and NREM sleep in control and asthmatic children (n = 134). Asthma classification was based on preestablished clinical criteria. Multivariate linear regression model was built to control for potential confounders (significance level P ≤ 0.05). Results. Our data demonstrated that (1) baseline nocturnal respiratory parameters were not significantly different in asthmatic versus control children, (2) the maximal % of SaO2 desaturation during REM, but not during NREM, was significantly higher in asthmatic children, and (3) multivariate analysis revealed that the association between asthma and REM-related maximal % SaO2 desaturation was independent of demographic variables. Conclusion. These results demonstrate that children with asthma have a REM-related vulnerability trait that impacts oxygenation independently of OSA. Further research is needed to delineate the REM sleep neurobiological mechanisms that modulate the phenotypical expression of nocturnal asthma in children. PMID:24288619

  18. EFFECTS OF CONTROLLED EXPOSURE TO DIESEL EXHAUST IN ALLERGIC ASTHMATIC INDIVIDUALS

    EPA Science Inventory

    After completing a study evaluating the effects of exposure to diesel exhaust (DE) and nitrogen dioxide (NO2) on the lower airways and blood of allergic asthmatic participants, investigators will have measured multiple physiologic and pulmonary function endpoints...

  19. RELATIONSHIP BETWEEN EXPOSURE DURATION AND SULFUR DIOXIDE-INDUCED BRONCHOCONSTRICTION IN ASTHMATIC SUBJECTS

    EPA Science Inventory

    The purpose of the study was to determine the shortest duration of exposure to 1.0 ppm sulfur dioxide (SO2) sufficient to induce bronchoconstriction significantly greater than that observed with exposure to clean air (CA) in exercising SO2 sensitive asthmatics. Asymptomatic, nonm...

  20. PULMONARY FUNCTION, AIRWAY RESPONSIVENSS, AND RESPIRATORY SYMPTOMS IN ASTHMATICS FOLLOWING EXERCISE IN NO2

    EPA Science Inventory

    Asthmatics performed three l0-min moderate exercises while exposed to 0.00 and 0.30 NO2. ollowing the initial exercise, FEV1 decreased to a greater extent (p<0.05) in NO2 than in air (7%). After the second and third exercises, decreases in FEV1 and FVC and increases in SRaw were ...

  1. Comparison of normal and asthmatic subjects' responses to sulfate pollutant aerosols

    SciTech Connect

    Utell, M.J.; Morrow, P.E.; Hyde, R.W.

    1980-01-01

    Epidemiological studies support an association between elevated levels of sulfates and acute respiratory disease. To determine if these pollutants produce airway hyperreactivity, 16 normal and 17 asthmatic subjects inhaled a control NaCl aerosol and the following sulfates: ammonium sulfate, sodium bisulfate, ammonium bisulfate, and sulfuric acid. A Lovelace generator produced particles with an average MMAD of approx. 1.0 ..mu..m (sigma/sub g/ approx. = 2.0) and concentrations of 0.1 and 1.0 mg/m/sup 3/. By double-blind randomization, all subjects breathed these aerosols for a 16-minute period. To determine if sulfate inhalation caused increased reactivity to a known bronchoconstrictor, all subjects inhaled carbachol following each 16-minute exposure. Before, during, and after exposure, pulmonary function studies were performed. When compared to NaCl, sulfate (1 mg/m/sup 3/) produced significant reductions in airway conductance and flow rates in asthmatics. The two most sensitive asthmatics demonstrated changes even at 0.1 mg/m/sup 3/ sulfate. To a far more significant degree, the bronchoconstrictor action of carbachol was potentiated by sulfates more or less in relation to their acidity in normals and asthmatics.

  2. Losartan may inhibit the progression of liver fibrosis in chronic HCV patients

    PubMed Central

    Salama, Zakaria A.; Sadek, Ahmed; Abdelhady, Ahmed M.; Morsy, Shereif Ahmed; Esmat, Gamal

    2016-01-01

    Background Abundant experimental evidence indicates overproduction of angiotensin II in the injured liver, and a role in stimulation of hepatic stellate cell (HSC) activation and fibrogenesis thereby, representing an attractive antifibrotic target. The aim of this study was to examine the antifibrotic effect of losartan on histopathologic level in chronic HCV patients. Methods A prospective study on fifty patients with chronic HCV and liver fibrosis proved by liver biopsy was conducted. They included patients who did not respond (n=36) or comply (n=2) or receive therapy due to established cirrhosis (n=10), or refused to receive (n=2) combined interferon and ribavirin therapy. They were divided randomly into 2 groups. The 1st group (n=25) was given losartan 50 mg OD for 1 year and the 2nd group (25 patients) was given silymarin, 140 mg t.i.d., (silymarin group). Liver biopsy was done at baseline and 1 year from the onset of treatment (end of study). Results In the second liver biopsy after 1 year, the decrease in fibrosis stage was significantly different between losartan group and silymarin group (a decrease of 1.88±0.96 (50.9%) vs. 0.45±0.93 (11.7%), respectively; P<0.01). In patients treated with losartan, regression in fibrosis stage was observed in 14/16 patients vs. 2/11 in silymarin group (P<0.01). No differences were observed in inflammation grades in both groups. A significant increase in albumin and prothrombin levels and a decrease in systolic blood pressure were found in losartan but not in silymarin group (P=0.009, 0.001 & 0.018 respectively and P=0.158, 0.603 & 0.288, respectively). Conclusions Histopathological scores showed that losartan had an inhibitory effect on progression and even led to regression of fibrosis stage but had no effect on the grade of inflammation. PMID:27275467

  3. Serum eosinophil cationic protein and bronchial hyperresponsiveness to hypoosmolar challenge in naive atopic asthmatics.

    PubMed

    Dal Negro, R; Tognella, S; Micheletto, C; Pomari, C; Burti, E; Mauroner, L; Turco, P

    1998-01-01

    Inhaled nonisotonic solutions (e.g., ultrasonically nebulized distilled water, UNDW) are sensitive bronchoconstrictive agents in asthmatics, their suggested mechanism of action being the release of mediators from some inflammatory cells. Studies assessing the relationship between degree of bronchial hyperresponsiveness to UNDW and plasma levels of eosinophilic markers are not available to date. Fourteen asymptomatic, nonsmoking, naive asthmatics (8 males, aged 18 to 45; mean basal FEV1 = 93.8% predicted +/- 1.7 SE), monosensitized to Dermatophagoides pteronyssinus, and twelve normal subjects (9 males, aged 19 to 40, mean basal FEV1 = 93.3% predicted +/- 1.4 SE) entered the study after informed consent. Each subject performed the UNDW challenge while the transcutaneous pO2 (PtcO2) was monitored. Serum eosinophil cationic protein (ECP) was measured together with blood eosinophils 60 min before UNDW. The bronchial response was expressed as FEV1 and PtcO2% drop from baseline, as assessed 10 min following UNDW. Mean blood eosinophils were 3.4% total leukocytes +/- 0.3 SE in normal subjects and 7.9% total leukocytes +/- 0.4 SE in asthmatics (p < 0.001). Mean serum ECP was 4.6 micrograms/l +/- 0.6 SE in normal subjects and 22.4 micrograms/l +/- 1.3 SE in asthmatics (p < 0.001). Mean FEV1 drop was 2.1% +/- 1.1 SE in normal subjects and 24.2% +/- 1.1 SE in asthmatics; the corresponding mean PtcO2% drop was 3.6 +/- 0.7 SE in normal subjects and 28.6 +/- 1.4 SE in asthmatics. Serum ECP was found to be related to blood eosinophils (r = 0.7, p = 0.003); despite the eosinophils, serum ECP proved to be related to a drop in both FEV1 and PtcO2, atr = 0.6 (p = 0.024) and r = 0.7 (p = 0.006), respectively. In conclusion, serum ECP, but not eosinophils per se, can differentiate normal subjects from naive asthmatics hyperresponsive to UNDW. Serum ECP was also proven to be directly related to both the UNDW-induced bronchoconstriction and hypoxemia, thus confirming that proximal, but

  4. Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition.

    PubMed

    Burger, Jan A; Landau, Dan A; Taylor-Weiner, Amaro; Bozic, Ivana; Zhang, Huidan; Sarosiek, Kristopher; Wang, Lili; Stewart, Chip; Fan, Jean; Hoellenriegel, Julia; Sivina, Mariela; Dubuc, Adrian M; Fraser, Cameron; Han, Yulong; Li, Shuqiang; Livak, Kenneth J; Zou, Lihua; Wan, Youzhong; Konoplev, Sergej; Sougnez, Carrie; Brown, Jennifer R; Abruzzo, Lynne V; Carter, Scott L; Keating, Michael J; Davids, Matthew S; Wierda, William G; Cibulskis, Kristian; Zenz, Thorsten; Werner, Lillian; Dal Cin, Paola; Kharchencko, Peter; Neuberg, Donna; Kantarjian, Hagop; Lander, Eric; Gabriel, Stacey; O'Brien, Susan; Letai, Anthony; Weitz, David A; Nowak, Martin A; Getz, Gad; Wu, Catherine J

    2016-01-01

    Resistance to the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules. Using whole-exome and deep-targeted sequencing, we dissect evolution of ibrutinib resistance in serial samples from five chronic lymphocytic leukaemia patients. In two patients, we detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300, MLL2 and EIF2A), with one patient developing trans-differentiation into CD19-negative histiocytic sarcoma. Using droplet-microfluidic technology and growth kinetic analyses, we demonstrate the presence of ibrutinib-resistant subclones and estimate subclone size before treatment initiation. Haploinsufficiency of TRAIL-R, a consequence of del(8p), results in TRAIL insensitivity, which may contribute to ibrutinib resistance. These findings demonstrate that the ibrutinib therapy favours selection and expansion of rare subclones already present before ibrutinib treatment, and provide insight into the heterogeneity of genetic changes associated with ibrutinib resistance. PMID:27199251

  5. Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition

    PubMed Central

    Burger, Jan A.; Landau, Dan A.; Taylor-Weiner, Amaro; Bozic, Ivana; Zhang, Huidan; Sarosiek, Kristopher; Wang, Lili; Stewart, Chip; Fan, Jean; Hoellenriegel, Julia; Sivina, Mariela; Dubuc, Adrian M.; Fraser, Cameron; Han, Yulong; Li, Shuqiang; Livak, Kenneth J.; Zou, Lihua; Wan, Youzhong; Konoplev, Sergej; Sougnez, Carrie; Brown, Jennifer R.; Abruzzo, Lynne V.; Carter, Scott L.; Keating, Michael J.; Davids, Matthew S.; Wierda, William G.; Cibulskis, Kristian; Zenz, Thorsten; Werner, Lillian; Cin, Paola Dal; Kharchencko, Peter; Neuberg, Donna; Kantarjian, Hagop; Lander, Eric; Gabriel, Stacey; O'Brien, Susan; Letai, Anthony; Weitz, David A.; Nowak, Martin A.; Getz, Gad; Wu, Catherine J.

    2016-01-01

    Resistance to the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules. Using whole-exome and deep-targeted sequencing, we dissect evolution of ibrutinib resistance in serial samples from five chronic lymphocytic leukaemia patients. In two patients, we detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300, MLL2 and EIF2A), with one patient developing trans-differentiation into CD19-negative histiocytic sarcoma. Using droplet-microfluidic technology and growth kinetic analyses, we demonstrate the presence of ibrutinib-resistant subclones and estimate subclone size before treatment initiation. Haploinsufficiency of TRAIL-R, a consequence of del(8p), results in TRAIL insensitivity, which may contribute to ibrutinib resistance. These findings demonstrate that the ibrutinib therapy favours selection and expansion of rare subclones already present before ibrutinib treatment, and provide insight into the heterogeneity of genetic changes associated with ibrutinib resistance. PMID:27199251

  6. Inhibition of peripheral blood neutrophil oxidative burst in periodontitis patients with a homeopathic medication Traumeel S

    PubMed Central

    žilinskas, Juozas; žekonis, Jonas; žekonis, Gediminas; Šadzevičienė, Renata; Sapragonienė, Marija; Navickaitė, Justina; Barzdžiukaitė, Ingrida

    2011-01-01

    Summary Background The anti-inflammatory effects of a homeopathic remedy, Traumeel S, have been observed in experimental and clinical studies; however, its antioxidant properties have not been elucidated. The aim of the present study was to evaluate the antioxidant effects of Traumeel S on peripheral blood neutrophils in patients with periodontitis. Material/Methods The study was performed using venous blood of 22 individuals with chronic periodontitis and 21 healthy subjects. The antioxidant effects of Traumeel S on the production of reactive oxygen species by unstimulated and stimulated with unopsonized E. coli neutrophils were investigated using luminol- and lucigenin-dependent chemiluminescence (CL). Results Polymorphonuclear leukocytes of periodontitis patients produced higher levels (p<0.01) of light output of lucigenin-dependent chemiluminescence and significantly reduced (p<0.01) light output of luminol-dependent chemiluminescence than analogous cells of healthy subjects. Highly diluted (10−4 of the stem solution) Traumeel S significantly (by approximately 50%) reduced superoxide-induced oxidation of lucigenin by unstimulated and stimulated with unopsonized E. coli polymorphonuclear leukocytes of periodontitis patients and had a tendency to intensify luminol-dependent chemiluminescence. Preincubation of the unstimulated and stimulated with unopsonized E. coli polymorphonuclear leukocytes of healthy subjects with Traumeel S exerts no inhibitory action on the luminol- and lucigenin-dependent chemiluminescence of the above-mentioned cells. Conclusions This study indicates that Traumeel S may significantly reduce production of superoxide anion by unstimulated and stimulated peripheral blood polymorphonuclear neutrophils of periodontitis patients. PMID:21525811

  7. The transcription factor PU.1 promotes alternative macrophage polarization and asthmatic airway inflammation.

    PubMed

    Qian, Feng; Deng, Jing; Lee, Yong Gyu; Zhu, Jimmy; Karpurapu, Manjula; Chung, Sangwoon; Zheng, Jun-Nian; Xiao, Lei; Park, Gye Young; Christman, John W

    2015-12-01

    The transcription factor PU.1 is involved in regulation of macrophage differentiation and maturation. However, the role of PU.1 in alternatively activated macrophage (AAM) and asthmatic inflammation has yet been investigated. Here we report that PU.1 serves as a critical regulator of AAM polarization and promotes the pathological progress of asthmatic airway inflammation. In response to the challenge of DRA (dust mite, ragweed, and Aspergillus) allergens, conditional PU.1-deficient (PU/ER(T)(+/-)) mice displayed attenuated allergic airway inflammation, including decreased alveolar eosinophil infiltration and reduced production of IgE, which were associated with decreased mucous glands and goblet cell hyperplasia. The reduced asthmatic inflammation in PU/ER(T)(+/-) mice was restored by adoptive transfer of IL-4-induced wild-type (WT) macrophages. Moreover, after treating PU/ER(T)(+/-) mice with tamoxifen to rescue PU.1 function, the allergic asthmatic inflammation was significantly restored. In vitro studies demonstrate that treatment of PU.1-deficient macrophages with IL-4 attenuated the expression of chitinase 3-like 3 (Ym-1) and resistin-like molecule alpha 1 (Fizz-1), two specific markers of AAM polarization. In addition, PU.1 expression in macrophages was inducible in response to IL-4 challenge, which was associated with phosphorylation of signal transducer and activator of transcription 6 (STAT6). Furthermore, DRA challenge in sensitized mice almost abrogated gene expression of Ym-1 and Fizz-1 in lung tissues of PU/ER(T)(+/-) mice compared with WT mice. These data, all together, indicate that PU.1 plays a critical role in AAM polarization and asthmatic inflammation. PMID:26101328

  8. Quantitative assessment of multiscale structural and functional alterations in asthmatic populations

    PubMed Central

    Hoffman, Eric A.; Wenzel, Sally E.; Castro, Mario; Fain, Sean B.; Jarjour, Nizar N.; Schiebler, Mark L.; Chen, Kun

    2015-01-01

    Relationships between structural and functional variables in asthmatic lungs at local and global (or lobar) levels remain to be discovered. This study aims to investigate local alterations of structural variables [bifurcation angle, circularity, airway wall thickness (WT), and hydraulic diameter (Dh)] in asthmatic subjects, and their correlations with other imaging and pulmonary function test-based global and lobar metrics, including lung shape, air-trapping, regional volume change, and more. Sixty-one healthy subjects, and 67 nonsevere and 67 severe asthmatic subjects were studied. The structural variables were derived from computed tomography images at total lung capacity (TLC). Air-trapping was measured at functional residual capacity, and regional volume change (derived from image registration) was measured between functional residual capacity and TLC. The tracheal diameter and WT predicted by 61 healthy subjects were used to normalize the Dh and WT. New normalization schemes allowed for the dissociation of luminal narrowing and wall thickening effects. In severe asthmatic subjects, the alteration of bifurcation angle was found to be correlated with a global lung shape at TLC, and circularity was significantly decreased in the right main bronchus. While normalized WT increased especially in the upper lobes of severe asthmatic subjects, normalized Dh decreased in the lower lobes. Among local structural variables, normalized Dh was the most representative variable, because it was significantly correlated with alterations of functional variables, including pulmonary function test's data. In conclusion, understanding multiscale phenomena may help to provide guidance in the search for potential imaging-based phenotypes for the development and outcomes assessment of therapeutic intervention. PMID:25814641

  9. Microbial content of household dust associated with exhaled NO in asthmatic children

    PubMed Central

    Johansson, Elisabet; Reponen, Tiina; Vesper, Stephen; Levin, Linda; Lockey, James; Ryan, Patrick; Bernstein, David I.; Villareal, Manuel; Hershey, Gurjit K. Khurana; Schaffer, Chris; LeMasters, Grace

    2013-01-01

    Exhaled nitric oxide (eNO) is increasingly used as a non-invasive measure of airway inflammation. Despite this, little information exists regarding the potential effects of indoor microbial components on eNO. We determined the influence of microbial contaminants in house dust and other indoor environmental characteristics on eNO levels in seven-year-olds with and without a physician- diagnosis of asthma. The study included 158 children recruited from a birth cohort study, and 32 were physician-diagnosed as asthmatic. The relationship between eNO levels and exposures to home dust streptomycetes, endotoxin, and molds was investigated. Streptomycetes and endotoxin were analyzed both as loads and concentrations in separate models. Dog, cat, and dust mite allergens also were evaluated. In the multivariate exposure models high streptomycetes loads and concentrations were significantly associated with a decrease in eNO levels in asthmatic (p <0.001) but not in healthy children. The presence of dog allergen, however, was associated with increased levels of eNO (p = 0.001). Dust endotoxin was not significant. The relationship between eNO and indoor exposure to common outdoor molds was u-shaped. In non-asthmatic children, none of the exposure variables were significantly associated with eNO levels. To our knowledge, this is the first study demonstrating a significant association between microbial components in the indoor environment and eNO levels in asthmatic children. This study demonstrates the importance of simultaneously assessing multiple home exposures of asthmatic children to better understand opposing effects. Common components of the indoor Streptomyces community may beneficially influence airway inflammation. PMID:23807177

  10. An angiotensin I-converting enzyme insertion/deletion polymorphism is associated with Pakistani asthmatic cases and controls.

    PubMed

    Saba, Nusrat; Yusuf, Osman; Rehman, Sadia; Munir, Saeeda; Ahmad, Sheeraz; Mansoor, Atika; Raja, Ghazala K

    2016-09-01

    Asthma is a chronic disease due to inflammation of the airways of lungs that is clinically characterized by variable symptoms including wheezing, coughing and shortness of breath. Angiotensin I-converting enzyme (ACE) plays a major role in fibrous tissue formation and is highly expressed in lungs. The main aim of this research work was to study the role of ACE insertion/deletion (I/D) polymorphism, rs4646994, in asthma in Pakistani patients. A total of 854 subjects, including 333 asthma patients and 521 ethnically matched controls, were studied. The ACE (I/D) polymorphism was genotyped using polymerase chain reaction (PCR). Chi-square, Fisher's exact and Hardy-Weinberg equilibrium tests were used to compare groups. Homozygous insertion genotype II (p less than 0.0001, OR=3.38) and insertion allele (I) was significantly more frequent in Pakistani asthmatics than in healthy controls (p=0.0007, OR=1.40). The ID genotype (p less than 0.0001, OR=0.43) and the deletion allele (D) were associated with protection of disease in Pakistani patients (p=0.0007, OR=0.71). These data suggest the involvement of ACE I/D polymorphism in asthma risk in the Pakistani population. This marker may be an important indication in the molecular mechanism of asthma and can become a useful tool in risk assessment and help in designing strategy to combat disease. PMID:27581935

  11. Circulating endothelin-1 levels in lean non-insulin-dependent diabetic patients. Influence of ACE inhibition.

    PubMed

    Ferri, C; Laurenti, O; Bellini, C; Faldetta, M R; Properzi, G; Santucci, A; De Mattia, G

    1995-01-01

    To evaluate the effect of captopril on plasma endothelin-1 (ET-1) levels and insulin sensitivity, 15 lean normotensive men (51.6 +/- 3.8 years) affected by non-insulin-dependent diabetes mellitus (NIDDM) underwent 2-h euglycemic hyperinsulinemic clamp. Each patient was then assigned to receive either captopril (25 mg twice daily for 1 week) or placebo, in a double-blind randomized fashion, before repeating clamp. At baseline, plasma ET-1 levels were 0.77 +/- 0.25 pg/mL in captopril (n = 10) and 0.83 +/- 0.3 pg/mL in placebo patients (n = 5). A twofold increase in plasma ET-1 levels occurred during the 2-h insulin infusion in both groups (P < .05 after 60 and 120 min), with a rapid return to baseline after 30 min from insulin withdrawal. After 1 week of therapy, total glucose uptake significantly increased in captopril (from 3.71 +/- 1.70 mg/kg/min to 4.24 +/- 1.72 mg/kg/min, P < .03) but not in placebo patients. Plasma ET-1 levels significantly decreased after captopril therapy (0.48 +/- 0.25 pg/mL at time 0, P < .03 v pretreatment levels), but were unaffected by placebo. Moreover, captopril slightly reduced the magnitude of ET-1 increment during insulin infusion (0.65 +/- 0.28 pg/mL and 0.88 +/- 0.48 pg/mL at 60 and 120 min, respectively, P < .05 v time 0). As a consequence, during the second insulin infusion circulating ET-1 levels were significantly lower in captopril- than in placebo-treated patients at time 0 (P < .02), 60 (P < .002), 120 (P < .004), and 150 min (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7734095

  12. A Proposal for Early Dosing Regimens in Heart Transplant Patients Receiving Thymoglobulin and Calcineurin Inhibition

    PubMed Central

    Barten, Markus J.; Schulz, Uwe; Beiras-Fernandez, Andres; Berchtold-Herz, Michael; Boeken, Udo; Garbade, Jens; Hirt, Stephan; Richter, Manfred; Ruhpawar, Arjang; Schmitto, Jan Dieter; Schönrath, Felix; Schramm, Rene; Schweiger, Martin; Wilhelm, Markus; Zuckermann, Andreas

    2016-01-01

    There is currently no consensus regarding the dose or duration of rabbit antithymocyte globulin (rATG) induction in different types of heart transplant patients, or the timing and intensity of initial calcineurin inhibitor (CNI) therapy in rATG-treated individuals. Based on limited data and personal experience, the authors propose an approach to rATG dosing and initial CNI administration. Usually rATG is initiated immediately after exclusion of primary graft failure, although intraoperative initiation may be appropriate in specific cases. A total rATG dose of 4.5 to 7.5 mg/kg is advisable, tailored within that range according to immunologic risk and adjusted according to immune monitoring. Lower doses (eg, 3.0 mg/kg) of rATG can be used in patients at low immunological risk, or 1.5 to 2.5 mg/kg for patients with infection on mechanical circulatory support. The timing of CNI introduction is dictated by renal recovery, varying between day 3 and day 0 after heart transplantation, and the initial target exposure is influenced by immunological risk and presence of infection. Rabbit antithymocyte globulin and CNI dosing should not overlap except in high-risk cases. There is a clear need for more studies to define the optimal dosing regimens for rATG and early CNI exposure according to risk profile in heart transplantation.

  13. A Proposal for Early Dosing Regimens in Heart Transplant Patients Receiving Thymoglobulin and Calcineurin Inhibition.

    PubMed

    Barten, Markus J; Schulz, Uwe; Beiras-Fernandez, Andres; Berchtold-Herz, Michael; Boeken, Udo; Garbade, Jens; Hirt, Stephan; Richter, Manfred; Ruhpawar, Arjang; Schmitto, Jan Dieter; Schönrath, Felix; Schramm, Rene; Schweiger, Martin; Wilhelm, Markus; Zuckermann, Andreas

    2016-06-01

    There is currently no consensus regarding the dose or duration of rabbit antithymocyte globulin (rATG) induction in different types of heart transplant patients, or the timing and intensity of initial calcineurin inhibitor (CNI) therapy in rATG-treated individuals. Based on limited data and personal experience, the authors propose an approach to rATG dosing and initial CNI administration. Usually rATG is initiated immediately after exclusion of primary graft failure, although intraoperative initiation may be appropriate in specific cases. A total rATG dose of 4.5 to 7.5 mg/kg is advisable, tailored within that range according to immunologic risk and adjusted according to immune monitoring. Lower doses (eg, 3.0 mg/kg) of rATG can be used in patients at low immunological risk, or 1.5 to 2.5 mg/kg for patients with infection on mechanical circulatory support. The timing of CNI introduction is dictated by renal recovery, varying between day 3 and day 0 after heart transplantation, and the initial target exposure is influenced by immunological risk and presence of infection. Rabbit antithymocyte globulin and CNI dosing should not overlap except in high-risk cases. There is a clear need for more studies to define the optimal dosing regimens for rATG and early CNI exposure according to risk profile in heart transplantation. PMID:27500271

  14. Inhibition of Angiofibromas in a Tuberous Sclerosis Patient Using Topical Timolol 0.5% Gel.

    PubMed

    Krakowski, Andrew C; Nguyen, Tuyet A

    2015-09-01

    Angiofibromas are the most recognized cutaneous manifestations of tuberous sclerosis complex. Angiofibromas can be associated with disfigurement, bleeding, pruritus, and erythema and may lead to significant psychosocial consequences for affected patients. Histopathologically, angiofibromas consist of a mixture of vascular and interstitial cells. Traditional treatment options include cryotherapy, electrocoagulation, radiofrequency ablation, dermabrasion, laser treatment, and topical agents such as podophyllotoxin. However, complications such as pain, postinflammatory hyperpigmentation, scarring, and the frequent recurrence rate reduce the utility of these treatment options. The introduction of topical rapamycin marked a turning point for treatment of facial angiofibromas; however, the lack of a standardized formulation, limited insurance coverage, and significant financial cost restrict universal access for patients and their caregivers. Both oral and topical β-blockers have proven extremely effective treatments for superficial vascular tumors such as hemangiomas and pyogenic granulomas. Topical β-blockers may potentially be useful for treatment of angiofibromas considering these lesions also contain a vascular component. Here we present an exploratory case report of a patient with tuberous sclerosis complex who had significant clinical improvement of her facial angiofibromas utilizing a "split-face" comparison protocol of topical timolol 0.5% gel after full-field treatment with ablative fractional laser resurfacing and pulsed-dye laser. PMID:26304829

  15. Pharmacological inhibition of p38 MAPK reduces tumor growth in patient-derived xenografts from colon tumors

    PubMed Central

    Papaioannou, Marilena; Lopez-Casas, Pedro Pablo; Llonch, Elisabet; Hidalgo, Manuel; Gorgoulis, Vassilis G.; Nebreda, Angel R.

    2015-01-01

    Colorectal cancer is a major health problem and the second cause of cancer related death in western countries. Signaling pathways that control tissue homeostasis are often deregulated during tumorigenesis and contribute to tumor development. Studies in mouse models have shown that the p38 MAPK pathway regulates homeostasis in colon epithelial cells but also plays an important role in colon tumor maintenance. In this study, we have investigated the role of p38 MAPK signaling in patient-derived xenografts (PDXs) from three different human colon tumors representing clinical heterogeneity and that recapitulate the human tumor conditions both at histological and molecular levels. We have found that PH797804, a chemical inhibitor of p38 MAPK, reduces tumor growth of the three PDXs, which correlates with impaired colon tumor cell proliferation and survival. The inhibition of p38 MAPK in PDXs results in downregulation of the IL-6/STAT3 signaling pathway, which is a key regulator of colon tumorigenesis. Our results show the importance of p38 MAPK in human colon tumor growth using a preclinical model, and support that inhibition of p38 MAPK signaling may have therapeutic interest for colon cancer treatment. PMID:25890501

  16. The Microbial Capsular Polysaccharide Galactoxylomannan Inhibits IL-17A Production in Circulating T Cells from Rheumatoid Arthritis Patients

    PubMed Central

    Pericolini, Eva; Alunno, Alessia; Gabrielli, Elena; Bartoloni, Elena; Cenci, Elio; Chow, Siu-Kei; Bistoni, Giovanni; Casadevall, Arturo; Gerli, Roberto; Vecchiarelli, Anna

    2013-01-01

    The persistence of activated T cells in rheumatoid arthritis (RA) synovium may be attributable to increased homing, increased retention or a possible imbalance between cell proliferation and programmed cell death. Induction of apoptosis may represent a potential therapeutic approach. Galactoxylomannan (GalXM) from the opportunistic fungus Cryptococcus neoformans can interact with T cells and induce T-cell apoptosis through the inhibition of CD45 phosphatase activity. The aim of this study was to determine the effect of GalXM on circulating T cells from patients with RA and the underlying mechanisms. GalXM immunomodulating effect on apoptosis and signal transduction pathway involved in IL-17A production was evaluated on T cells. RA T-cell apoptosis, higher than that of control T cells, was further increased by GalXM through induction of caspase-3 activation. Activated T cells expressing the CD45RO molecule and producing IL-17A were the main target of GalXM-induced apoptosis. GalXM induced consistent impairment of IL-17A production and inhibition of STAT3, which was hyperactivated in RA. In conclusion, GalXM triggered apoptosis of activated memory T cells and interfered with IL-17A production in RA. These data suggest therapeutic targeting of deleterious Th17 cells in RA and other autoimmune diseases. PMID:23308194

  17. Biofilm Filtrates of Pseudomonas aeruginosa Strains Isolated from Cystic Fibrosis Patients Inhibit Preformed Aspergillus fumigatus Biofilms via Apoptosis

    PubMed Central

    Shirazi, Fazal; Ferreira, Jose A. G.; Stevens, David A.; Clemons, Karl V.; Kontoyiannis, Dimitrios P.

    2016-01-01

    Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) colonize cystic fibrosis (CF) patient airways. Pa culture filtrates inhibit Af biofilms, and Pa non-CF, mucoid (Muc-CF) and nonmucoid CF (NMuc-CF) isolates form an ascending inhibitory hierarchy. We hypothesized this activity is mediated through apoptosis induction. One Af and three Pa (non-CF, Muc-CF, NMuc-CF) reference isolates were studied. Af biofilm was formed in 96 well plates for 16 h ± Pa biofilm filtrates. After 24 h, apoptosis was characterized by viability dye DiBAc, reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, DNA fragmentation and metacaspase activity. Muc-CF and NMuc-CF filtrates inhibited and damaged Af biofilm (p<0.0001). Intracellular ROS levels were elevated (p<0.001) in NMuc-CF-treated Af biofilms (3.7- fold) compared to treatment with filtrates from Muc-CF- (2.5- fold) or non-CF Pa (1.7- fold). Depolarization of mitochondrial potential was greater upon exposure to NMuc-CF (2.4-fold) compared to Muc-CF (1.8-fold) or non-CF (1.25-fold) (p<0.0001) filtrates. Exposure to filtrates resulted in more DNA fragmentation in Af biofilm, compared to control, mediated by metacaspase activation. In conclusion, filtrates from CF-Pa isolates were more inhibitory against Af biofilms than from non-CF. The apoptotic effect involves mitochondrial membrane damage associated with metacaspase activation. PMID:26930399

  18. Cimicifuga foetida L. plus adefovir effectively inhibits the replication of hepatitis B virus in patients with chronic hepatitis B

    PubMed Central

    DAI, XIUFANG; YI, XIANFU; SUN, ZEQUN; RUAN, PENG

    2016-01-01

    The aim of the present study was to assess the anti-hepatitis B virus (HBV) effect of Cimicifuga foetida L. (C. foetida) in the patients with chronic hepatitis B (CHB). A total of 60 randomly selected patients with CHB were recruited and divided into groups I and II. The patients in group I received a monotherapy of adefovir (ADV), and the patients in group II received a combination therapy of ADV and C. foetida for >48 weeks. Intrahepatic (IH) HBV covalently closed circular DNA (cccDNA), serum HBV DNA, hepatitis B surface antigen (HBsAg), alanine aminotransferase levels and serum interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) levels were quantified during the test. Following the treatment, a significant reduction of the median IH cccDNA level was identified in group II (P=0.017), but not in group I (P=0.05, and P=0.01 between the 2 groups), and a significant reduction of log10 HBsAg was identified in groups I (P=0.012) and II (P<0.0001, and P=0.20 between the 2 groups). A significant increase of the median serum IFN-γ level was found in group II (P=0.0005), but not in group I (P=0.06, and P=0.004 between the 2 groups), and a significant reduction of the median TGF-β level was identified in groups I (P<0.0001) and II (P<0.0001, and P=0.002 between the 2 groups). A total of 24 patients in group I, and 27 patients in group II achieved a sustained virological response (P=0.0386), and 20 patients in group I and 24 in group II achieved hepatitis B e antigen seroclearance (P=0.0442). In conclusion, C. foetida can effectively inhibit HBV transcription and replication in the patients by stimulating the release of the inflammatory cytokines, such as IFN-γ. PMID:27073640

  19. A Clinical Audit of the Management of Acute Asthmatic Attacks in Adults and Children Presenting to an Emergency Department

    PubMed Central

    Dasgupta, S; Williams, EW; Walters, C; Eldemire-Shearer, D; Williams-Johnson, J

    2014-01-01

    Objective: To compare the guidelines in the University Hospital of the West Indies (UHWI) acute asthma management protocol with actual practice in the Accident and Emergency Department. Methods: A prospective docket audit was done of all consecutive medical records of patients, presenting with a diagnosed acute asthmatic attack between June 1 and September 30, 2010, to the emergency department of the UHWI. A convenient sample was used. The audit tool used was created from the UHWI protocol for the emergency management of asthma in adults and children, as well as the British Adult Asthma Audit Tool. The audit tool assessed three main sections: initial assessment, initial management, and discharge considerations. Data were coded and entered in Microsoft Excel 2007 and statistical analyses conducted using Stata version 10. Management patterns were compared to the actual protocol and then discussed. Results: A total of 15 864 patients were seen during the study period. Of these, a total of 293 patients were seen for a presentation of acute asthma. More females (57.3%) than males were seen, with the mean age of 33.53 years. Only 31% of patients were given a severity assessment of mild, moderate, or severe. Peak expiratory flow rate (PEFR) was attempted and recorded in 62%, but only 18.1% of patients had both pre and post PEFR done. Only 4.4% of patients were administered nebulizations within the suggested time frame. Positively, 94.2% of patients were given a prescription for inhaled corticosteroids and bronchodilators to continue post-discharge. Conclusion: Acute asthma management still remains an area of medical practice that continues to have long-standing difficulties. Failure to assess and document the severity of asthma attacks along with the under-utilization of PEFR was noted. PMID:25314279

  20. Inhibition of the colonic motor response to eating by pinaverium bromide in irritable bowel syndrome patients.

    PubMed

    Fioramonti, J; Frexinos, J; Staumont, G; Bueno, L

    1988-01-01

    The effect of pinaverium bromide on the colonic motor response to eating was investigated in 10 irritable bowel syndrome patients, by means of an intraluminal probe supporting 8 groups of electrodes. At each site examined from transverse to sigmoid colon, the electromyograms exhibited 2 kinds of spike bursts: short spike bursts (SSB) localized at one electrode, and long spike bursts (LSB), isolated, propagated orally or aborally over a few centimeters, or aborally propagated over the whole length of the colon investigated (migrating long spike bursts, MLSB). Recordings were continuously performed over 24 hr. Each patient received at 7.00 p.m. on day 1 and at noon on day 2 an 800-1000 Kcal meal preceded by IV administration of pinaverium bromide (4 mg) or placebo. After placebo administration, the duration of LSB activity and the number of MLSB were significantly increased over 3 postprandial hr by comparison with the 2 hr preceding the meal. After pinaverium injection no significant postprandial change in LSB and MLSB activity was noted. The SSB activity was not modified after the meals preceded by placebo or pinaverium injection. These results suggest that the inhibitory action of pinaverium bromide on postprandial colonic motility may support the clinical efficacy of this agent in the treatment of the irritable bowel syndrome. PMID:3371838

  1. Immediate Effects of Inhibitive Distraction on Active Range of Cervical Flexion in Patients with Neck Pain: A Pilot Study

    PubMed Central

    Briem, Kristín; Huijbregts, Peter; Thorsteinsdottir, Maria

    2007-01-01

    The purpose of this pilot study was to examine the immediate effects of a manual therapy technique called Inhibitive Distraction (ID) on active range of motion (AROM) for cervical flexion in patients with neck pain with or without concomitant headache. A secondary objective of this study was to see whether patient subgroups could be identified who might benefit more from ID by studying variables such as age, pain intensity, presence of headache, or pre-intervention AROM. We also looked at patients' ability to identify pre- to post-intervention changes in their ability to actively move through a range of motion. Forty subjects (mean age 34.7 years; range 16–48 years) referred to a physical therapy clinic due to discomfort in the neck region were randomly assigned to an experimental and a control group. We used the CROM goniometer to measure pre- and post-intervention cervical flexion AROM in the sagittal plane within a single treatment session. The between-group difference in AROM increase was not statistically significant at P<0.05 with a mean post-intervention increase in ROM of 2.4° (SD 6.2°) for the experimental group and 1.2° (SD 5.8°) for the placebo group. We were also unable to identify potential subgroups more likely to respond to ID, although a trend emerged for greater improvement in chronic patients with headaches, lower pain levels, and less pre-intervention AROM. In the experimental group and in both groups combined, subjects noting increased AROM indeed had a significantly greater increase in AROM than those subjects not noting improvement. In conclusion, this study did not confirm immediate effects of ID on cervical flexion AROM but did provide indications for potential subgroups likely to benefit from this technique. Recommendations are provided with regard to future research and clinical use of the technique studied. PMID:19066648

  2. Understanding Environmental Tobacco Smoke Exposure and Effects in Asthmatic Children through Determination of Urinary Cotinine and Targeted Metabolomics of Plasma

    EPA Science Inventory

    Understanding Environmental Tobacco Smoke Exposure and Effects in Asthmatic Children through Determination of Urinary Cotinine and Targeted Metabolomics of Plasma Introduction Asthma is a complex disease with multiple triggers and causal factors, Exposure to environmental tob...

  3. miR-125b inhibits goblet cell differentiation in allergic airway inflammation by targeting SPDEF.

    PubMed

    Liu, Zhaoe; Chen, Xing; Wu, Qiaoling; Song, Jia; Wang, Lijun; Li, Gang

    2016-07-01

    Asthma is a disease characterized by goblet cell differentiation, mucus hypersecretion, airway inflammation, and airway hyperresponsiveness. miR-125b was downregulated as normal human bronchial epithelial cells differentiation to pseudostratified epithelium. However, its role in asthma remains unknown especially in regulating goblet cell differentiation. miR-125b expression in the sputum of 50 asthmatic children and 50 age- and sex-matched healthy controls were assessed by quantitative RT-PCR (qRT-PCR). Meanwhile, expressions of miR-125b and SAM pointed domain-containing ETS transcription factor (SPDEF) in normal human tracheal epithelial (HTEpC) and A549 cells stimulated with lipopolysaccharide (LPS) for 2h were detected by qRT-PCR and western blot. Furthermore, the predicted miR-125b target was determined in silico and confirmed with dual-luciferase reporter assay. Additionally, intranasal delivery of miR-125b mimic in mice was performed to study its effects on house dust mite-induced allergic airway inflammation mouse models. We found that miR-125b expression was decreased in the sputum of the asthmatic patients especially in eosinophilic asthma. After stimulation with LPS, miR-125b expression was downregulated, accompanied by the upregulation of SPDEF in HTEpC and A549 cells. Moreover, SPDEF is a target of miR-125b, which regulates SPDEF at the posttranscriptional level. Additionally, intranasal delivery of miR-125b decreased SPDEF protein levels, goblet cell differentiation, mucus hypersecretion, and altered relevant gene expressions. Taken together, these results suggest that miR-125b inhibits SPDEF expression modulating goblet cell differentiation and mucus secretion in asthma. PMID:27112664

  4. Effects of Montelukast on free radical production in whole blood and isolated human polymorphonuclear neutrophils (PMNs) in asthmatic children

    PubMed Central

    Al Saadi, Muslim M.; Meo, Sultan Ayoub; Mustafa, Ali; Shafi, Ahmed; Tuwajri, Ali S. Al

    2011-01-01

    Montelukast is a highly selective leukotriene-receptor antagonist (LTRA). It is widely used in the treatment of bronchial asthma, primarily as an adjunct to corticosteroids. Reactive oxygen species (ROSs) play an important role in the pathogenesis of asthma and oxidative stress contributing to the initiation and worsening of inflammatory respiratory disorders, such as asthma. Antioxidant drugs may have a role in minimizing or preventing damage in asthmatic children. The aim of this study was to assess the antioxidant effect of montelukast on the production of free radicals in the whole blood and polymorphonuclear neutrophils (PMNs) in asthmatic children. A group of 48 (38 males and 10 females), apparently healthy asthmatic children were recruited with ages ranging between 6 and 14 years. In asthmatic children, base line (premedication) and post medication free radicals activity in the whole blood and polymorphonuclear neutrophils (PMNs) was determined by measuring chemiluminescence (CL) response through chemiluminescence luminometer. Free radical productions were significantly decreased in the whole blood, when stimulated with Phorbol Myristate Acetate (p < 0.04) and Opsonised Zymosan (p < 0.05). The free radicals were also significantly decreased in isolated polymorphonuclear neutrophils (PMNs) when stimulated with Opsonised Zymosan (p < 0.05) after the post medication treatment of montelukast in asthmatic children. Montelukast decreased the reactive oxygen species production, both in the whole blood as well as isolated PMNs in asthmatic children. PMID:23960762

  5. Single-cell gel electrophoresis assay of nasal epithelium and leukocytes from asthmatic and nonasthmatic subjects in Mexico City.

    PubMed

    Fortoul, Teresa Imelda; Valverde, Mahara; López, Maria del Carmen; Bizarro, Patricia; López, Irma; Sánchez, Ivonne; Colín-Barenque, Laura; Avila-Costa, Maria Rosa; Rojas, Emilio; Ostrosky-Shejet, Patricia

    2003-06-01

    The prevalence of asthma--a chronic inflammatory respiratory disease--is increasing worldwide. One hypothesis suggests that this trend is related to enhanced exposure to air pollutants. Chronic inflammation generates oxidative stress, and cells involved in an allergic reaction are capable of producing reactive oxygen species that may predispose asthmatics to increased deoxyribonucleic acid (DNA) damage. The authors estimated DNA strand breaks by use of single-cell gel electrophoresis assay on 2 different cell types (i.e., nasal epithelial cells and leukocytes) sampled from asthmatic and nonasthmatic medical students in Mexico City. The authors found that asthmatic subjects had more DNA breaks in their nasal epithelial cells than did their nonasthmatic counterparts. In contrast, asthmatic subjects had less damage in their leukocytes than did nonasthmatic individuals. These findings suggest that the hyperreactivity of the nasal epithelium prevents systemic effects from air pollutants, as reflected by less DNA injury to leukocytes of the asthmatic group. Asthmatic's nasal epithelial cells were more sensitive to DNA damage than were those of nonasthmatics--perhaps as a consequence of increased fragility induced either by air pollution or by a chronic inflammatory response. PMID:14992309

  6. Tetraspanin 7 (TSPAN7) expression is upregulated in multiple myeloma patients and inhibits myeloma tumour development in vivo

    SciTech Connect

    Cheong, Chee Man; Chow, Annie W.S.; Fitter, Stephen; Hewett, Duncan R.; Martin, Sally K.; Williams, Sharon A.; To, L. Bik; and others

    2015-03-01

    Background: Increased expression of the tetraspanin TSPAN7 has been observed in a number of cancers; however, it is unclear how TSPAN7 plays a role in cancer progression. Methods: We investigated the expression of TSPAN7 in the haematological malignancy multiple myleoma (MM) and assessed the consequences of TSPAN7 expression in the adhesion, migration and growth of MM plasma cells (PC) in vitro and in bone marrow (BM) homing and tumour growth in vivo. Finally, we characterised the association of TSPAN7 with cell surface partner molecules in vitro. Results: TSPAN7 was found to be highly expressed at the RNA and protein level in CD138{sup +} MM PC from approximately 50% of MM patients. TSPAN7 overexpression in the murine myeloma cell line 5TGM1 significantly reduced tumour burden in 5TGM1/KaLwRij mice 4 weeks after intravenous adminstration of 5TGM1 cells. While TSPAN7 overexpression did not affect cell proliferation in vitro, TSPAN7 increased 5TGM1 cell adhesion to BM stromal cells and transendothelial migration. In addition, TSPAN7 was found to associate with the molecular chaperone calnexin on the cell surface. Conclusion: These results suggest that elevated TSPAN7 may be associated with better outcomes for up to 50% of MM patients. - Highlights: • TSPAN7 expression is upregulated in newly-diagnosed patients with active multiple myeloma. • Overexpression of TSPAN7 inhibits myeloma tumour development in vivo. • TSPAN7 interacts with calnexin at the plasma membrane in a myeloma cell line.

  7. Exogenous nitric oxide inhibits Rho-associated kinase activity in patients with angina pectoris: a randomized controlled trial

    PubMed Central

    Maruhashi, Tatsuya; Noma, Kensuke; Fujimura, Noritaka; Kajikawa, Masato; Matsumoto, Takeshi; Hidaka, Takayuki; Nakashima, Ayumu; Kihara, Yasuki; Liao, James K; Higashi, Yukihito

    2016-01-01

    The RhoA/Rho-associated kinase (ROCK) pathway has a key physiological role in the pathogenesis of atherosclerosis. Increased ROCK activity is associated with cardiovascular diseases. Endogenous nitric oxide (NO) has an anti-atherosclerotic effect, whereas the exogenous NO-mediated cardiovascular effect still remains controversial. The purpose of this study was to evaluate the effect of exogenous NO on ROCK activity in patients with angina pectoris. This is a prospective, open-label, randomized, controlled study. A total of 30 patients with angina pectoris were randomly assigned to receive 40 mg day−1 of isosorbide mononitrate (n = 15, 12 men and 3 women, mean age of 63 ± 12 years, isosorbide mononitrate group) or conventional treatment (n = 15, 13 men and 2 women, mean age of 64 ± 13 years, control group) for 12 weeks. ROCK activity in peripheral leukocytes was measured by western blot analysis. ROCK activities at 4 and 12 weeks after treatment were decreased in the isosorbide mononitrate group (0.82 ± 0.33 at 0 week, 0.62 ± 0.20 at 4 weeks, 0.61 ± 0.19 at 12 weeks, n = 15 in each group, P < 0.05, respectively) but not altered in the control group. ROCK1 and ROCK2 expression levels were similar in all treatment periods in the two groups. These findings suggest that the administration of exogenous NO can inhibit ROCK activity, indicating that the usage of exogenous NO could have a protective effect in patients with angina pectoris. PMID:25740292

  8. Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children

    PubMed Central

    Erdem, Semiha Bahceci; Nacaroglu, Hikmet Tekin; Unsal Karkiner, Canan Sule; Gunay, Ilker; Can, Demet

    2015-01-01

    Background: Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well. Objectives: The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma. Patients and Methods: 1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric. Results: Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect. Conclusions: The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals. PMID:26495098

  9. Electrophysiological manifestations of stimulus evaluation, response inhibition and motor processing in Tourette syndrome patients

    PubMed Central

    Thibault, Genevieve; O’Connor, Kieron P.; Stip, Emmanuel; Lavoie, Marc E.

    2013-01-01

    Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder with childhood onset presenting with multiple fluctuating motor tics and one or more phonic tics. A significant proportion of people suffering from GTS are still symptomatic in adulthood and present other emotional and cognitive difficulties, along with motor problems that often accompany these comorbid conditions. The nature of these difficulties is still poorly understood and multiple comorbidities are often inadequately controlled. The current study investigates both stimulus evaluation and motor processing in GTS while controlling for comorbidity. Fifteen adults with GTS and 20 control participants were matched on gender, laterality and intelligence. The P300 component, the no-go anteriorization (NGA) as well as the stimulus and response-locked lateralized-readiness potentials (S-LRP, R-LRP) were elicited during a stimulus–response compatibility (SRC) paradigm. The standard version of the Stroop Color–Word Test (SCWT) was also administered. Reaction times showed that participants with GTS processed both the SRC and the SCWT more rapidly than the control group, while producing a delayed P300 peak latency. The GTS group also showed faster S-LRP onset in response to the incompatible and faster processing of interference in the SCWT. There was also a tendency toward a greater frontal shift of the NGA in the GTS group. The P300 latency showed that with GTS patients, stimulus evaluation occurs later whereas the overlapping pre-motor response selection processes occur faster. Our findings are congruent with a probable cortical motor over-activation hypothesis of GTS involving faster motor program selection in processing conflicting SR configuration. PMID:19395047

  10. Short-term effects of low-level winter pollution on respiratory health of asthmatic adults

    SciTech Connect

    Neukirch, F.; Segala, C.; Korobaeff, M.; Le Moullec, Y.; Aubier, M.

    1998-09-01

    The authors studied the short-term effects of Paris winter air pollution (i.e., sulfur dioxide, Black Smoke, suspended particulates with an aerodynamic diameter close to 10 {micro}m, and nitrogen dioxide) in 40 nonsmoking mild to moderate asthmatics. During a 6-mo period, subjects recorded asthma symptoms and three daily peak expiratory flow measurements. Statistical analysis revealed consistent and significant associations between the pollutants and asthma attacks and symptoms in the entire study group, especially in the subgroup of individuals who took inhaled {beta}2 agonists as needed. Pollutants correlated negatively with morning peak expiratory flow in the subgroup that took inhaled {beta}2 agonists as needed, and they correlated positively with daily variability in asthmatics who received regularly scheduled inhaled {beta}2 agonists. The effects lingered several days after exposure occurred. Low-level pollution has consistent measurable effects on nonsmoking adults who have well-treated mild or moderate asthma.

  11. Differing response of asthmatics to sulfur dioxide exposure with continuous and intermittent exercise

    SciTech Connect

    Kehrl, H.R.; Roger, L.J.; Hazucha, M.J.; Horstman, D.H.

    1986-08-29

    Ten mild asthmatics were initially exposed in an environmental chamber (26 C, 70% RH) to clean air and 1.0 ppm sulfur dioxide while performing three sets of 10 minutes treadmill exercise (ventilation = 41 1/min) and 15 minutes rest. To evaluate the effects of the pattern and duration of exercise on the response to sulfur dioxide exposure, the subjects were then exposed to the same environmental conditions, while exercising continuously for 30 minutes. Specific airways resistance (SRaw) was measured by body plethysmography prior to exposures and after each exercise. All SRaw responses with sulfur dioxide exposure were significantly different than the clean air responses. It appears that asthmatics show an attenuated response to repetitive exercise in a 1.00 ppm sulfur dioxide atmosphere and that the response to sulfur dioxide exposure develops rapidly and is maintained during 30 minutes continuous exercise.

  12. Relationship of social support to stress responses and immune function in healthy and asthmatic adolescents.

    PubMed

    Kang, D H; Coe, C L; Karaszewski, J; McCarthy, D O

    1998-04-01

    Although most clinicians believe that social support has beneficial effects on health, the mechanisms mediating this relationship have not been clearly established. We examined the direct effect of social support on several immune measures and its role in moderating the response to academic exams in healthy and asthmatic adolescents. Three types of students--healthy, mild asthma, and severe asthma--completed social support and stress questionnaires and gave blood samples during the midsemester and final exam periods. Social support and natural killer cell (NK) function showed a significant reduction during exams in both healthy and asthmatic adolescents. Social support, however, did not have a direct effect on immune responses. Nevertheless, high social support appeared to attenuate the magnitude of exam-induced reduction in NK activity, suggesting a role for social support in protecting against immune decrements during times of stress. PMID:9535404

  13. AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived xenografts of ovarian cancer

    PubMed Central

    Pépin, David; Sosulski, Amanda; Zhang, Lihua; Wang, Dan; Vathipadiekal, Vinod; Hendren, Katherine; Coletti, Caroline M.; Yu, Aaron; Castro, Cesar M.; Birrer, Michael J.; Gao, Guangping; Donahoe, Patricia K.

    2015-01-01

    To improve ovarian cancer patient survival, effective treatments addressing chemoresistant recurrences are particularly needed. Mullerian inhibiting substance (MIS) has been shown to inhibit the growth of a stem-like population of ovarian cancer cells. We have recently engineered peptide modifications to human MIS [albumin leader Q425R MIS (LRMIS)] that increase production and potency in vitro and in vivo. To test this novel therapeutic peptide, serous malignant ascites from highly resistant recurrent ovarian cancer patients were isolated and amplified to create low-passage primary cell lines. Purified recombinant LRMIS protein successfully inhibited the growth of cancer spheroids in vitro in a panel of primary cell lines in four of six patients tested. Adeno-associated virus (AAV) -delivered gene therapy has undergone a clinical resurgence with a good safety profile and sustained gene expression. Therefore, AAV9 was used as a single i.p. injection to deliver LRMIS to test its efficacy in inhibiting growth of palpable tumors in patient-derived ovarian cancer xenografts from ascites (PDXa). AAV9-LRMIS monotherapy resulted in elevated and sustained blood concentrations of MIS, which significantly inhibited the growth of three of five lethal chemoresistant serous adenocarcinoma PDXa models without signs of measurable or overt toxicity. Finally, we tested the frequency of MIS type II receptor expression in a tissue microarray of serous ovarian tumors by immunohistochemistry and found that 88% of patients bear tumors that express the receptor. Taken together, these preclinical data suggest that AAV9-LRMIS provides a potentially well-tolerated and effective treatment strategy poised for testing in patients with chemoresistant serous ovarian cancer. PMID:26216943

  14. AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived xenografts of ovarian cancer.

    PubMed

    Pépin, David; Sosulski, Amanda; Zhang, Lihua; Wang, Dan; Vathipadiekal, Vinod; Hendren, Katherine; Coletti, Caroline M; Yu, Aaron; Castro, Cesar M; Birrer, Michael J; Gao, Guangping; Donahoe, Patricia K

    2015-08-11

    To improve ovarian cancer patient survival, effective treatments addressing chemoresistant recurrences are particularly needed. Mullerian inhibiting substance (MIS) has been shown to inhibit the growth of a stem-like population of ovarian cancer cells. We have recently engineered peptide modifications to human MIS [albumin leader Q425R MIS (LRMIS)] that increase production and potency in vitro and in vivo. To test this novel therapeutic peptide, serous malignant ascites from highly resistant recurrent ovarian cancer patients were isolated and amplified to create low-passage primary cell lines. Purified recombinant LRMIS protein successfully inhibited the growth of cancer spheroids in vitro in a panel of primary cell lines in four of six patients tested. Adeno-associated virus (AAV) -delivered gene therapy has undergone a clinical resurgence with a good safety profile and sustained gene expression. Therefore, AAV9 was used as a single i.p. injection to deliver LRMIS to test its efficacy in inhibiting growth of palpable tumors in patient-derived ovarian cancer xenografts from ascites (PDXa). AAV9-LRMIS monotherapy resulted in elevated and sustained blood concentrations of MIS, which significantly inhibited the growth of three of five lethal chemoresistant serous adenocarcinoma PDXa models without signs of measurable or overt toxicity. Finally, we tested the frequency of MIS type II receptor expression in a tissue microarray of serous ovarian tumors by immunohistochemistry and found that 88% of patients bear tumors that express the receptor. Taken together, these preclinical data suggest that AAV9-LRMIS provides a potentially well-tolerated and effective treatment strategy poised for testing in patients with chemoresistant serous ovarian cancer. PMID:26216943

  15. Homes of low-income minority families with asthmatic children have increased condition issues

    PubMed Central

    Ciaccio, Christina E.; Nazir, Niaman; Daley, Christine M.; DiDonna, Anita; Choi, Won S.; Barnes, Charles S.; Rosenwasser, Lanny J.

    2014-01-01

    The home is increasingly associated with asthma. It acts both as a reservoir of asthma triggers and as a refuge from seasonal outdoor allergen exposure. Racial/ethnic minority families with low incomes tend to reside in neighborhoods with low housing quality. These families also have higher rates of asthma. This study explores the hypothesis that black and Latino urban households with asthmatic children experienced more home mechanical, structural condition–related areas of concern than white households with asthmatic children. Participant families (n = 140) took part in the Kansas City Safe and Healthy Homes Program, had at least one asthmatic child, and met income qualifications of no more than 80% of local median income; many were below 50%. Families self-identified their race. Homes were assessed by environmental health professionals using a standard set of criteria and a specific set of on-site and laboratory sampling and analyses. Homes were given a score for areas of concern between 0 (best) and 53 (worst). The study population self-identified as black (46%), non-Latino white (26%), Latino (14.3%), and other (12.9%). Mean number of areas of concern were 18.7 in Latino homes, 17.8 in black homes, 13.3 in other homes, and 13.2 in white homes. Latino and black homes had significantly more areas of concern. White families were also more likely to be in the upper portion of the income. In this set of 140 low-income homes with an asthmatic child, households of minority individuals had more areas of condition concerns and generally lower income than other families. PMID:25584914

  16. Effects of the inhaled treatment of liriope radix on an asthmatic mouse model.

    PubMed

    Kim, Ki-Suk; Cho, Dong-Hyuk; Yang, Hea Jung; Choi, Eun-Kyeong; Shin, Min Hee; Kim, Kang-Hoon; Ahn, Kwang Seok; Ha, In Jin; Na, Yun-Cheol; Um, Jae Young; Chung, Won Seok; Jung, Hee-Jae; Jung, Sung-Ki; Jang, Hyeung-Jin

    2015-01-01

    As a treatment for allergic asthma, inhaled treatments such as bronchodilators that contain β2-agonists have an immediate effect, which attenuates airway obstructions and decreases airway hypersensitivity. However, bronchodilators only perform on a one off basis, but not consistently. Asthma is defined as a chronic inflammatory disease of the airways accompanying the overproduction of mucus, airway wall remodeling, bronchial hyperreactivity and airway obstruction. Liriope platyphylla radix extract (LPP), a traditional Korean medicine, has been thoroughly studied and found to be an effective anti-inflammatory medicine. Here, we demonstrate that an inhaled treatment of LPP can attenuate airway hyperresponsiveness (AHR) in an ovalbumin-induced asthmatic mouse model, compared to the saline-treated group (p < 0.01). Moreover, LPP decreases inflammatory cytokine levels, such as eotaxin (p < 0.05), IL-5 (p < 0.05), IL-13 (p < 0.001), RANTES (p < 0.01), and TNF-α (p < 0.05) in the bronchoalveolar lavage (BAL) fluid of asthmatic mice. A histopathological study was carried out to determine the effects of LPP inhalation on mice lung tissue. We performed UPLC/ESI-QTOF-MS, LC/MS, and GC/MS analyses to analyze the chemical constituents of LPP, finding that these are ophiopogonin D, spicatoside A, spicatoside B, benzyl alcohol, and 5-hydroxymethylfurfural. This study demonstrates the effect of an inhaled LPP treatment both on airway AHR and on the inflammatory response in an asthmatic mouse model. Hence, LPP holds significant promise as a nasal inhalant for the treatment of asthmatic airway disease. PMID:25967662

  17. Quantitative PCR Analysis of Molds in the Dust from Homes of Asthmatic Children in North Carolina

    SciTech Connect

    Vesper, Stephen J.; McKinstry, Craig A.; Ashley, Peter; Haugland, Richard A.; Yeatts, Karin; Bradham, Karen; Svendsen, Eric

    2007-07-10

    The vacuum cleaner bag (VCB) dust from the homes of 19 asthmatic children in North Carolina (NC) was analyzed by mold specific quantitative PCR. These results were compared to the analysis of the VCB dust from 157 homes in the HUD “American Healthy Home Survey” of homes in the US. The American Relative Moldiness Index (ARMI) was calculated for each of the homes. The mean and standard deviation (SD) of the ARMI values in the homes of the NC asthmatic children was 11.0 (5.3), compared to the HUD survey VCB ARMI value mean and SD of 6.6 (4.4). The median ARMI value was significantly higher(p < 0.001) in the asthmatic childrens’s homes. The molds Chaetomium globosum and Eurotium amsterdameli were the primary species in the NC homes making the ARMI values higher. Vacuum cleaner bag dust samples may be a less expensive but still useful method of home mold analysis.

  18. Mechanisms of Heightened Airway Sensitivity and Responses to Inhaled SO2 in Asthmatics

    PubMed Central

    Reno, Anita L; Brooks, Edward G; Ameredes, Bill T

    2015-01-01

    Sulfur dioxide (SO2) is a problematic inhalable air pollutant in areas of widespread industrialization, not only in the United States but also in countries undergoing rapid industrialization, such as China, and it can be a potential trigger factor for asthma exacerbations. It is known that asthmatics are sensitive to the effects of SO2; however, the basis of this enhanced sensitivity remains incompletely understood. A PubMed search was performed over the course of 2014, encompassing the following terms: asthma, airway inflammation, sulfur dioxide, IL-10, mouse studies, and human studies. This search indicated that biomarkers of SO2 exposure, SO2 effects on airway epithelial cell function, and animal model data are useful in our understanding of the body’s response to SO2, as are SO2-associated amplification of allergic inflammation, and potential promotion of neurogenic inflammation due to chemical irritant properties. While definitive answers are still being sought, these areas comprise important foci of consideration regarding asthmatic responses to inhaled SO2. Furthermore, IL-10 deficiency associated with asthma may be another important factor associated with an inability to resolve inflammation and mitigate oxidative stress resulting from SO2 inhalation, supporting the idea that asthmatics are predisposed to SO2 sensitivity, leading to asthma exacerbations and airway dysfunction. PMID:25922579

  19. Acid fog: effects on respiratory function and symptoms in healthy and asthmatic volunteers

    SciTech Connect

    Hackney, J.D.; Linn, W.S.; Avol, E.L.

    1989-02-01

    Acidic air pollutants generally are dissolved in water droplets. Mean droplet diameter may range from more than 10 microns in dense fog to less than 1 micron at low relative humidity. Droplet size influences the deposition of inhaled acid within the respiratory tract and thus may influence toxicity. To help assess health risks from acid pollution, we performed controlled exposures of normal and asthmatic volunteers to sulfuric acid aerosols at nominal concentrations of 0 (control), 500, 1000, and 2000 micrograms/m/sup 3/. Exposures lasted 1 hr with intermittent heavy exercise. Response was assessed by lung function tests and symptom questionnaires. Under foggy conditions (mean droplet size 10 microns, temperature 50 degrees F), no marked effects on lung function were found. However, both normal and asthmatic subjects showed statistically significant dose-related increases in respiratory symptoms. In a separate study, normal subjects exposed at 70 degrees F with mean droplet size 0.9 microns showed no marked effect on function or symptoms. Asthmatics showed dose-related decrements in forced expiratory performance and increases in symptoms, most obvious at 1000 and 2000 micrograms/m/sup 3/. The different results of the two studies probably reflect an influence of droplet size, but further investigation is needed to confirm this. The aggregate results suggest that only mild, if any, short-term respiratory irritant effects are likely at acid concentrations attained in ambient pollution.

  20. Dynamics of eosinophil infiltration in the bronchial mucosa before and after the late asthmatic reaction.

    PubMed

    Aalbers, R; de Monchy, J G; Kauffman, H F; Smith, M; Hoekstra, Y; Vrugt, B; Timens, W

    1993-06-01

    We wanted to determine whether changes in bronchial hyperresponsiveness (BHR) following allergen challenge show a time relationship with inflammatory events in the airways of allergic asthmatic subjects. Lavage was performed and endobronchial biopsies were taken via the fiberoptic bronchoscope, before, and 3 and 24 h after, allergen challenge, on separate occasions, in nine dual asthmatic responders. The numbers of activated eosinophils, identified by immunohistochemistry, using the monoclonal anti-eosinophil cationic protein antibody, EG2, were significantly increased both at 3 h and at 24 h in the submucosa and bronchial lavage. A significant negative correlation was found between the number of EG2+ cells in the submucosa and in the bronchial lavage 24 h after the allergen challenge (r = -0.70). At 24 h, the amount of eosinophil cationic protein (ECP) was increased in the bronchial lavage. A significant correlation was observed between the amount of ECP at 3 h and the log provocative dose of house dust mite producing a 20% fall in forced expiratory volume in one second (PD20 HDM) (r = -0.63). The results suggest a recruitment of activated eosinophils to the submucosa and, further, to the epithelial lining, followed by degranulation. This process has already started 3 h after allergen challenge, and lasts for at least 24 h, which may result in mucosal damage and subsequent allergen-induced increase in BHR, before and after the late asthmatic reaction. PMID:8339804

  1. The asthmatic athlete: inhaled Beta-2 agonists, sport performance, and doping.

    PubMed

    McKenzie, Donald C; Fitch, Kenneth D

    2011-01-01

    The asthmatic athlete has a long history in competitive sport in terms of success in performance and issues related to doping. Well documented are detailed objective tests used to evaluate the athlete with symptoms of asthma or airway hyperresponsiveness and the medical management. Initiated at the 2002 Salt Lake City Games, the International Olympic Committee's Independent Asthma Panel required testing to justify the use of inhaled beta-2 agonists (IBAs) in Olympic athletes and has provided valuable guidelines to the practicing physician. This program was educational and documented the variability in prevalence of asthma and/or airway hyperresponsiveness and IBA use between different sports and different countries. It provided a standard of care for the athlete with respiratory symptoms and led to the discovery that asthmatic Olympic athletes outperformed their peers at both Summer and Winter Olympic Games from 2002 to 2010. Changes to the World Anti-Doping Agency's Prohibited List in 2010 permitted the use of 2 IBA produced by the same pharmaceutical company. All others remain prohibited. However, there is no pharmacological difference between the permitted and prohibited IBAs. As a result of these changes, asthmatic athletes are being managed differently based on a World Anti-Doping Agency directive that has no foundation in pharmacological science or in clinical practice. PMID:21200170

  2. Total Body Metabolic Tumor Response in ALK Positive Non-Small Cell Lung Cancer Patients Treated with ALK Inhibition

    PubMed Central

    Koole, Michel J. B.; Bongaerts, Alphons H. H.; Pruim, Jan; Groen, Harry J. M.

    2016-01-01

    Background In ALK-positive advanced NSCLC, crizotinib has a high response rate and effectively increases quality of life and survival. CT measurement of the tumor may insufficiently reflect the actual tumor load changes during targeted therapy with crizotinib. We explored whether 18F-FDG PET measured metabolic changes are different from CT based changes and studied the impact of these changes on disease progression. Methods 18F-FDG PET/CT was performed prior to and after 6 weeks of crizotinib treatment. Tumor response on CT was classified with RECIST 1.1, while 18F-FDG PET response was assessed according to the 1999 EORTC recommendations and PERCIST criteria. Agreement was assessed using McNemars test. During follow-up, patients received additional PET/CT during crizotinib treatment and second generation ALK inhibition. We assessed whether PET was able to detect progression earlier then CT. Results In this exploratory study 15 patients were analyzed who were treated with crizotinib. There was a good agreement in the applicability of CT and 18F-FDG PET/CT using the EORTC recommendations. During first line crizotinib and subsequent second line ALK inhibitors, PET was able to detect progression earlier then CT in 10/22 (45%) events of progression and in the others disease progression was detected simultaneously. Conclusion In advanced ALK positive NSCLC PET was able to detect progressive disease earlier than with CT in nearly half of the assessments while both imaging tests performed similar in the others. PMID:27137772

  3. [Classification of allergens by positive percentage agreement and cluster analysis based on specific IgE antibodies in asthmatic children].

    PubMed

    Iwasaki, E; Baba, M

    1992-10-01

    Classification and characterization of allergens is important because allergic patients are sensitized by a variety of allergens. One hundred and sixty-one sera from asthmatic children were investigated for specific IgE antibodies against 35 allergens including 20 inhalants and 15 foods by means of the MAST method. We assessed the allergenic properties of the allergens based on positive percentage agreement and cluster analysis. There was a high positive percentage agreement of specific IgE antibodies between house dust and Dermatophagoides spp., a relatively high agreement between 5 molds, cat and dog epithelium, mugwort and wormwood and 5 grasses. Among the food allergens, the positive percentage agreements were relatively high, especially between cow's milk, casein, cheese, and between 3 cereal grains. In the cluster analysis, house dust and Dermatophagoides spp. made a big cluster; therefore 32 allergens except house dust and mites were analyzed. From the results of the cluster analysis, the major cluster consisted of (1) ragweed, (2) mugwort and wormwood, (3) timothy, sweet vernal, velvet and cultivated rye, (4) wheat, barley and rice, (5) molds, (6) cow's milk, casein, soybean and cheese, (7) shrimp and crab, (8) egg white, (9) Japanese cedar, (10) dog epithelium, (11) cat epithelium. The cluster of grass pollens and cereal grains made one cluster. These results tend to confirm the presence of species cross-reactivities within the major classes of allergens. PMID:1482294

  4. Investigating the Relation Between Prevalence of Asthmatic Allergy with the Characteristics of the Environment Using Association Rule Mining

    NASA Astrophysics Data System (ADS)

    Kanani Sadat, Y.; Karimipour, F.; Kanani Sadat, A.

    2014-10-01

    The prevalence of allergic diseases has highly increased in recent decades due to contamination of the environment with the allergy stimuli. A common treat is identifying the allergy stimulus and, then, avoiding the patient to be exposed with it. There are, however, many unknown allergic diseases stimuli that are related to the characteristics of the living environment. In this paper, we focus on the effect of air pollution on asthmatic allergies and investigate the association between prevalence of such allergies with those characteristics of the environment that may affect the air pollution. For this, spatial association rule mining has been deployed to mine the association between spatial distribution of allergy prevalence and the air pollution parameters such as CO, SO2, NO2, PM10, PM2.5, and O3 (compiled by the air pollution monitoring stations) as well as living distance to parks and roads. The results for the case study (i.e., Tehran metropolitan area) indicates that distance to parks and roads as well as CO, NO2, PM10, and PM2.5 is related to the allergy prevalence in December (the most polluted month of the year in Tehran), while SO2 and O3 have no effect on that.

  5. Functional Restoration of Amyotrophic Lateral Sclerosis Patient-Derived Mesenchymal Stromal Cells Through Inhibition of DNA Methyltransferase.

    PubMed

    Oh, Youn Seo; Kim, Seung Hyun; Cho, Goang-Won

    2016-05-01

    Alteration of DNA methylation is highly associated with aging and neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS). Remedying these aberrant methylation patterns may serve to improve these diseases. Previously, we reported that human bone marrow mesenchymal stromal cells isolated from ALS patients (ALS-MSCs) have functionally decreased stem cell potency, and excessively express DNA methyltransferases (DNMTs). In this study, we examined the correlation between excessive DNMT expression and functional decline in ALS-MSCs. The DNMT inhibitor RG108 was used for this. RG108-treated ALS-MSCs exhibit increased expression of the anti-senescence genes TERT, VEGF, and ANG, and decreased expression of the senescence-related genes ATM and p21. The activity of SA-β-galactosidase and the expression of senescence proteins p53 and p16 were reduced in RG108-treated ALS-MSCs. The abilities of cell migration and protection against oxidative damage were improved in the treated ALS-MSCs. In neuronal differentiation experiments, the treated MSCs more effectively differentiated into neuron-like cells. These results suggest that ALS-MSC function can be restored by inhibiting excessively expressed DNMTs, an approach that may ultimately provide better efficacy in stem cell therapy. PMID:26210997

  6. HB-EGF-Promoted Airway Smooth Muscle Cells and Their Progenitor Migration Contribute to Airway Smooth Muscle Remodeling in Asthmatic Mouse.

    PubMed

    Wang, Qing; Li, Hequan; Yao, Yinan; Lu, Guohua; Wang, Yuehong; Xia, Dajing; Zhou, Jianying

    2016-03-01

    The airway smooth muscle (ASM) cells' proliferation, migration, and their progenitor's migration are currently regarded as causative factors for ASM remodeling in asthma. Heparin-binding epidermal growth factor (HB-EGF), a potent mitogen and chemotactic factor, could promote ASM cell proliferation through MAPK pathways. In this study, we obtained primary ASM cells and their progenitors from C57BL/6 mice and went on to explore the role of HB-EGF in these cells migration and the underlying mechanisms. We found that recombinant HB-EGF (rHB-EGF) intratracheal instillation accelerated ASM layer thickening in an OVA-induced asthmatic mouse. Modified Boyden chamber assay revealed that rHB-EGF facilitate ASM cell migration in a dose-dependent manner and ASM cells from asthmatic mice had a greater migration ability than that from normal counterparts. rHB-EGF could stimulate the phosphorylation of ERK1/2 and p38 in ASM cells but further migration assay showed that only epidermal growth factor receptor inhibitor (AG1478) or p38 inhibitor (SB203580), but not ERK1/2 inhibitor (PD98059), could inhibit rHB-EGF-mediated ASM cells migration. Actin cytoskeleton experiments exhibited that rHB-EGF could cause actin stress fibers disassembly and focal adhesions formation of ASM cells through the activation of p38. Finally, airway instillation of rHB-EGF promoted the recruitment of bone marrow-derived smooth muscle progenitor cells, which were transferred via caudal vein, migrating into the airway from the circulation. These observations demonstrated that ASM remodeling in asthma might have resulted from HB-EGF-mediated ASM cells and their progenitor cells migration, via p38 MAPK-dependent actin cytoskeleton remodeling. PMID:26826248

  7. Induction of immune tolerance in asthmatic mice by vaccination with DNA encoding an allergen-cytotoxic T lymphocyte-associated antigen 4 combination.

    PubMed

    Zhang, Fang; Huang, Gang; Hu, Bo; Song, Yong; Shi, Yi

    2011-05-01

    Allergen-specific immunotherapy is a potential treatment for allergic diseases. We constructed an allergen-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-encoding DNA vaccine, administered it directly to antigen-presenting cells (APCs), and investigated its ability and mechanisms to ameliorate allergic airway inflammation in an asthmatic mouse model. An allergen-CTLA-4 DNA plasmid (OVA-CTLA-4-pcDNA₃.₁) encoding an ovalbumin (OVA) and the mouse CTLA-4 extracellular domain was constructed and transfected into COS-7 cells to obtain the fusion protein OVA-CTLA-4, which was able to bind the B7 ligand on dendritic cells (DCs), and induced CD25⁺ Foxp3⁺ regulatory T (Treg) cells by the coculture of naive CD4⁺ T cells with DCs in vitro. In an animal study, BALB/c mice were sensitized and challenged with OVA to establish the asthmatic model. Vaccination with a high dose of OVA-CTLA-4-pcDNA₃.₁ significantly decreased interleukin-4 (IL-4) and IL-5 levels and eosinophil counts and prevented OVA-induced reduction of the gamma interferon level in the bronchoalveolar lavage fluid. In addition, these mice suffered less severe airway inflammation and had lower levels of OVA-specific IgE and IgG1 titers in serum. Also, high-dose OVA-CTLA-4-pcDNA₃.₁ vaccination inhibited the development of airway hyperreactivity and prevented OVA-induced reduction of the percentages of Foxp3⁺ Treg cells in the spleen. Our results indicate that a high dose of allergen-CTLA-4-encoding DNA vaccine was more effective in preventing an allergen-induced Th2-skewed immune response through the induction of Treg cells and may be a new alternative therapy for asthma. PMID:21346053

  8. [Associations between bioaerosols coming from livestock facilities and asthmatic symptoms in children].

    PubMed

    Hoopmann, M; Hehl, O; Neisel, F; Werfel, T

    2006-01-01

    Although health effects of occupational exposures to livestock emissions are known, potential associations between living in the neighbourhood of intensive livestock facilities and the risk of developing respiratory or allergic diseases are still under discussion. During routine school entry examinations in selected rural districts in Lower Saxony we asked parents about respiratory and allergic symptoms of their 5-6 year old children. A questionnaire with standardised questions of the ISAAC-Studies for respiratory and allergic symptoms and corresponding risk factors was used. Complementarily the children were examined for visible signs of flexural dermatitis and in a subsample the SX1-test was used as an in vitro test for inhalative IgE mediated sensibilisations in capillary blood. Individual exposure to bioaerosols (endotoxin, fungi, bacteria and total dust) coming from livestock facilities was estimated using a Lagrange dispersion model based on the emission rates and locations of the lifestock facilities. A total of 7943 questionnaires (response rate over 85%) were analysed, of which 3867 could be used for the correlation analyses between exposition to endotoxin and asthmatic symptoms. Multivariate logistic regression models were analyzed, considering an atopic disease of the parents as a potential effect modifier and not as a confounder. The prevalence of allergic and asthmatic symptoms is similar to the results of other comparable studies, e. g. "wheezing in the last 12 months" 15.9% for boys and 12.9% for girls. An increase in the prevalence of asthmatic symptoms for higher endotoxin levels was observed only for children of atopic parents. The multivariate controlled odds ratio for one unit logarithm endotoxin concentrations is 1.15, p-value 0.016. Similar effects were observed for other asthma indicators, but not for subjective criteria of the exposition, e. g. the distance to the next large livestock facility guesstimated by parents. Among the overall

  9. Decreased percentage of CD4+Foxp3+TGF-β+ and increased percentage of CD4+IL-17+ cells in bronchoalveolar lavage of asthmatics

    PubMed Central

    2014-01-01

    Background Asthma is a chronic inflammatory disorder of the airways with the proven role of Th2 cells in its pathogenesis. The role and characteristic of different subsets of CD4+ cells is much less known. Aim The aim of the study was to analyze the incidence of different subsets of CD4+ T cells, in particular different subsets of CD4+ cells with the co-expression of different cytokines. Methods Twenty five stable asthmatic and twelve age-matched control subjects were recruited to the study. Bronchoscopy and bronchoalveolar lavage (BAL) were performed in all study subjects. CD4+ T cells were isolated from BAL fluid by positive magnetic selection. After stimulation simultaneous expression of TGF-β, FoxP3, CD25, IFN-γ, IL-4, TNF-α (set 1); IL-10, FoxP3, CD25, IFN-γ, IL-4, MIP-1β (set 2); IL-17A, IL-8, IFN-γ, IL-4, MIP-1β (set 3) were measured by flow cytometry. Results The percentage of CD4+ cells co-expressing Foxp3 and TGF-β (CD4+Foxp3+TGF-β+ cells) was significantly lower (P = 0.03), whereas the percentage of CD4+IL-17+ cells (P = 0.008), CD4+IL-17+ IFN-γ+ cells (P = 0.047) and CD4+IL-4+ cells (P = 0.01) were significantly increased in asthmatics compared with that seen in healthy subjects. A significantly higher percentage of CD4+Foxp3+ cells from asthma patients expressed IFN-γ (P = 0.01), IL-4 (P = 0.004) and CD25 (P = 0.04), whereas the percentage of CD4+IL-10+ cells expressing Foxp3 was significantly decreased in asthmatics (P = 0.03). FEV1% predicted correlated negatively with the percentage of CD4+IL-17+ cells (r = -0.33; P = 0.046) and positively with CD4+Foxp3+TGF-β+ cells (r = 0.43; P = 0.01). Conclusions Our results suggest that in the airways of chronic asthma patients there is an imbalance between increased numbers of CD4+IL-17+ cells and Th2 cells and decreased number of CD4+Foxp3+TGF-β+. PMID:25132806

  10. Modulation of adhesion molecule expression on endothelial cells during the late asthmatic reaction: role of macrophage-derived tumour necrosis factor-alpha.

    PubMed Central

    Lassalle, P; Gosset, P; Delneste, Y; Tsicopoulos, A; Capron, A; Joseph, M; Tonnel, A B

    1993-01-01

    In a previous work we have demonstrated that in patients exhibiting a late allergic reaction (LAR), alveolar macrophages (AM) collected 18 h after bronchial allergen challenge produced high levels of IL-6 and tumour necrosis factor-alpha (TNF) which is known to up-regulate the endothelial cell expression of adhesion molecules participating in the development of the inflammatory reaction in bronchial asthma. For these reasons, we evaluated the effect of AM supernatants from asthmatic patients developing an LAR on intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression by human endothelial cells. The expression of adhesion molecules was assessed by an ELISA method and compared with the effect of an optimal dose of human recombinant (hr) TNF. Results showed that AM supernatants, from challenged asthmatics developing an LAR, increased significantly the ICAM-1 and ELAM-1 expression on endothelial cells to a level similar to that obtained in the presence of hrTNF (500 U/ml) (P < 0.001 in both cases, respectively 90.4% and 75.2% of the level obtained with hrTNF). In contrast, AM supernatants from asthmatics at baseline or exhibiting, after challenge, a single early reaction had no significant effect on these parameters (P = NS in both cases, respectively 23.5% and 24.7% of the ICAM-1 expression, 22.7% and 15.3% of the ELAM-1 expression obtained with hrTNF). AM-derived TNF present in these supernatants was thought to play a key role in endothelial cell stimulation, since: (i) TNF concentration in AM supernatants correlated with its effect on ICAM-1 (r = 0.80, P < 10(-4)) and ELAM-1 expression (r = 0.88, P < 10(-5)); and (ii) a neutralizing anti-TNF antibody decreased their effect (68% and 80% respectively on ICAM-1 and ELAM-1 expression). Moreover, the role of IL-6 was excluded on the basis both of the hrIL-6 inefficiency to induce ICAM-1 and ELAM-1 synthesis, even in costimulation with hrTNF, and of anti-IL-6 antibody

  11. The treatment of the asthmatic mother during pregnancy and lactation.

    PubMed

    Spector, S L

    1983-08-01

    In summary, the management of asthma in the pregnant patient does not differ much from the management of asthma in a patient who is not pregnant. An awareness of how asthma medications affect the fetus is important since it is rare to reach the ideal management where no medication at all is given. The benefit to risk ratio must be considered for both mother and her fetus should be medication be required. Since hypoxemia is the greatest single danger to both the mother and fetus important medications should not be withheld and the physician should not wait too long. The mother should be counseled about avoiding medications that include tetracycline, iodine products, aspirin or non-steroidal anti-inflammatory agents, tartrazine, sedatives, and beta-adrenergic blocking agents. It is just as important to remember that alcohol and cigarettes are potent drugs or interact with other medications. Inapropriate exercise, irritants or allergens might also require counseling so that the pregnant mother can avoid them. A good common sense and caring approach of a physician to a well informed patient represents the most appropriate management of asthma in the pregnant patient and nursing mother. PMID:6410938

  12. Current and Future Treatment Strategies for Patients with Advanced Hepatocellular Carcinoma: Role of mTOR Inhibition.

    PubMed

    Finn, Richard S

    2012-11-01

    Hepatocellular carcinoma (HCC) is a common cancer that has the third highest cancer-related mortality rate worldwide. Although potentially curable by transplantation if detected early, the majority of cases are diagnosed at an advanced stage of disease for which limited treatment options are available. The only proven systemic therapy for advanced HCC is sorafenib, a multi-kinase inhibitor that has demonstrated modest efficacy and reasonable tolerability in patients with advanced HCC. Five years after the approval of sorafenib, no other agent has been proven to be beneficial in the first- or second-line setting in advanced HCC. While molecular studies have highlighted various potential targets in HCC, the mammalian target of rapamycin (mTOR) has emerged as an exciting target for cancer therapy including HCC. Laboratory data have linked the phosphatidylinositol 3-kinase/AKT/mTOR axis to various oncogenic processes, including survival and angiogenesis. Historically, mTOR inhibitors have been used for their immunosuppressive properties, but more recently they have been approved as anticancer agents. Retrospective HCC studies suggest that the inclusion of mTOR inhibition as part of an immunosuppressant regimen after transplantation may reduce HCC recurrence compared with other immunosuppressive agents such as calcineurin inhibitors. More recently, single-arm, phase I/II studies have shown that mTOR inhibitors also have activity as monotherapy in cases of recurrent HCC or de novo advanced HCC. This article will review the rationale for targeting the mTOR pathway in HCC, and the currently available clinical data supporting its development for HCC. PMID:24159589

  13. Fstl1 Promotes Asthmatic Airway Remodeling by Inducing Oncostatin M.

    PubMed

    Miller, Marina; Beppu, Andrew; Rosenthal, Peter; Pham, Alexa; Das, Sudipta; Karta, Maya; Song, Dae Jin; Vuong, Christine; Doherty, Taylor; Croft, Michael; Zuraw, Bruce; Zhang, Xu; Gao, Xiang; Aceves, Seema; Chouiali, Fazila; Hamid, Qutayba; Broide, David H

    2015-10-15

    Chronic asthma is associated with airway remodeling and decline in lung function. In this article, we show that follistatin-like 1 (Fstl1), a mediator not previously associated with asthma, is highly expressed by macrophages in the lungs of humans with severe asthma. Chronic allergen-challenged Lys-Cre(tg) /Fstl1(Δ/Δ) mice in whom Fstl1 is inactivated in macrophages/myeloid cells had significantly reduced airway remodeling and reduced levels of oncostatin M (OSM), a cytokine previously not known to be regulated by Fstl1. The importance of the Fstl1 induction of OSM to airway remodeling was demonstrated in murine studies in which administration of Fstl1 induced airway remodeling and increased OSM, whereas administration of an anti-OSM Ab blocked the effect of Fstl1 on inducing airway remodeling, eosinophilic airway inflammation, and airway hyperresponsiveness, all cardinal features of asthma. Overall, these studies demonstrate that the Fstl1/OSM pathway may be a novel pathway to inhibit airway remodeling in severe human asthma. PMID:26355153

  14. [Clinical effects of theophylline in the therapy of intractable asthmatic children. II. Theophylline therapy and behavior problems in children with asthma].

    PubMed

    Segawa, H; Iikura, Y

    1990-10-01

    This study examined the relationship between long-term theophylline therapy and behavior problems in 14 asthmatic children that includes 5 intractable cases and 24 non-asthmatic children. Asthmatic children have received theophylline therapy and cromolyn inhalation for 3.6 +/- 3.8 years. Subjects were tested on neuropsychologic batteries; behavior problems and personality of children questionnaire, child behavior checklist, caffeine-like side effects questionnaire, manifest anxiety scale, visual attention test, Uchida-Kraepelin test and soft neurological signs. These tests were repeated with an interval of 1 to 12 weeks. Parents noted caffeine-like side effects, stomach ache and difficulty in sleeping, in their child during the theophylline therapy. The caffeine-like side effects decreased after stopping theophylline therapy. The rate of mistake in Uchida-Kraepelin test for the asthmatic group and for the intractable cases was significantly higher than that of the control group. Time of the sequential finger thumb opposition of the soft neurological signs was significantly prolonged in asthmatic group. There was no significant change in the other tests between asthmatic and non-asthmatic children and before and after stopping theophylline therapy. It seems that behavior problems and learning disability observed in the asthmatic children are due to the pathogenesis or symptoms of asthma rather than the effect of long-term theophylline therapy. PMID:2124479

  15. Activation of Bcl-2-Caspase-9 Apoptosis Pathway in the Testis of Asthmatic Mice

    PubMed Central

    Li, Junjuan; Ding, Zhaolei; Sheng, Jianhui; Li, Juan; Tan, Wei

    2016-01-01

    Background Apoptosis plays a critical role in controlling the proliferation and differentiation of germ cells during spermatogenesis. Dysregulation of the fine-tuned balance may lead to the onset of testicular diseases. In this study, we investigated the activation status of apoptosis pathways in the testicular tissues under the background of an asthmatic mouse model. Methods Ten BALB/c mice were divided into two groups: the acute asthma group and the control group. In the acute asthma group, ovalbumin (OVA)-sensitized mice were challenged with aerosolized OVA for 7 days, while the control group was treated with physiological saline. After that, both epididymis and testis were collected to determine the sperm count and motility. Apoptosis in the testis was evaluated by DNA ladder, immunochemistry and further by PCR array of apoptosis-related genes. Finally, the cleavage of caspase-3 and poly ADP-ribose polymerase (PARP) was determined by western blot and the enzymatic activities of caspase-9 and 3/7 were assessed using Caspase-Glo kits. Results Compared with control mice, significant decreases in the body weight, testis weight, sperm count and motility were seen in the experimental group. DNA ladder and immunochemistry showed significant increase in apoptotic index of the asthmatic testis, whereas a decrease in mRNA expression of Bcl-2 and increases in Bax, BNIP3, caspase-9, and AIF were observed in the asthma group. Furthermore, protein levels of AIF were significantly upregulated, while the translational expression of Bcl-2 was downregulated markedly. Consistently, caspase-9 activity in the testis of asthma mice was significantly higher than that of the control group. Conclusion Collectively, these results showed that Bcl-2-caspase-9 apoptosis pathway was clearly activated in the testis of asthmatic mice with the increased expression of apoptosis-related genes and proteins. To our knowledge, this is the first report demonstrating that asthma could lead to the

  16. Airborne water droplets in mist or fog may affect nocturnal attacks in asthmatic children.

    PubMed

    Kashiwabara, Kosuke; Itonaga, Kotaro; Moroi, Toshihiro

    2003-06-01

    Our study objectives were to evaluate whether or not airborne water droplets in mist or fog affect the occurrence of nocturnal attacks of asthmatic children using a retrospective study. This study included 971 visits by children with bronchial asthma to the emergency department at nighttime (from 18:00 to 09:00) during a 3-year period (April 1, 1998-March 31, 2001). Meteorological data were checked at a local fire station and regional meteorological observatory. We divided nighttime into five 3-hour periods to evaluate the relationship between chronological changes in the frequency of the emergency department visits of asthmatic children and of meteorological conditions. In four of five periods of nighttime, multivariate analysis showed that mist or fog, average atmospheric temperature, and barometric pressure were related to the number of emergency department visits (n=1096, r=0.165-0.263, p<0.0001). We divided the year into four seasons to eliminate differences between atmospheric temperature and barometric pressure on clear nights and on misty or foggy nights; we also found the mean number of emergency department visits was higher on misty or foggy nights than on clear nights in each seasonal period (p<0.01). In addition, average atmospheric temperature on misty or foggy nights with the emergency department visits was higher than that on misty or foggy nights without any visits (p<0.01). Asthmatic children frequently visited the emergency department on misty or foggy nights, especially during midnight to dawn periods with high atmospheric temperature. Because a higher atmospheric temperature on misty or foggy nights indicates a larger saturated amount of airborne water droplets, our results suggest that mist and fog, in particular a saturated amount of airborne water droplets, may be a stimulus for bronchoconstriction. PMID:12870836

  17. Analysis of asthma patients for cryptococcal seroreactivity in an urban German area.

    PubMed

    Grahnert, Andreas; Müller, Uwe; von Buttlar, Heiner; Treudler, Regina; Alber, Gottfried

    2015-08-01

    Cryptococcus neoformans is an opportunistic fungal pathogen that causes lung inflammation and meningoencephalitis in immunocompromised patients but is also able to asymptomatically infect immunocompetent individuals. C. neoformans is found ubiquitously especially in urban areas where it is spread by pigeons, and fungal exposure may predispose for asthma development already at an early age, as soon as confronted with pigeon droppings. In the study presented here, we investigated the presence of specific immunoglobulin G (IgG) against C. neoformans in sera from patients suffering from asthma in comparison to a healthy control cohort, accrued from the Leipzig Research Centre for Civilization Diseases (LIFE). For serological analysis we developed a flow cytometry (FACS) based assay specific for an acapsular strain of C. neoformans to comprehensively analyze different cryptococcal serotypes. Compared with the non-asthmatic cohort, asthmatics exhibited, as expected, an elevated level of total serum immunoglobulin E (IgE), whereas the IgG seroreactivity against C. neoformans was not significantly different among the two groups (P = .118). Nevertheless, there was a trend toward increased Cryptococcus-specific IgG antibodies in the serum of asthmatics. Additionally, in male asthmatics an increased IgG-mediated seroreactivity compared to female asthmatics was found. This points to a higher prevalence of subclinical C. neoformans infection in male asthmatics and may support the hypothesis of C. neoformans as a risk factor for the development of asthma in urban areas. PMID:26026172

  18. Substantial Susceptibility of Chronic Lymphocytic Leukemia to BCL2 Inhibition: Results of a Phase I Study of Navitoclax in Patients With Relapsed or Refractory Disease

    PubMed Central

    Roberts, Andrew W.; Seymour, John F.; Brown, Jennifer R.; Wierda, William G.; Kipps, Thomas J.; Khaw, Seong Lin; Carney, Dennis A.; He, Simon Z.; Huang, David C.S.; Xiong, Hao; Cui, Yue; Busman, Todd A.; McKeegan, Evelyn M.; Krivoshik, Andrew P.; Enschede, Sari H.; Humerickhouse, Rod

    2012-01-01

    Purpose BCL2 overexpression is a hallmark of chronic lymphocytic leukemia (CLL). The novel BH3 mimetic navitoclax (ABT-263) specifically inhibits BCL2 and related proteins BCL-xl and BCL-w, potently inducing apoptosis of CLL cells in vitro. A phase I trial in patients with CLL was conducted to evaluate the safety, pharmacokinetics, and biologic activity of oral navitoclax. Patients and Methods Twenty-nine patients with relapsed or refractory CLL received daily navitoclax for 14 days (10, 110, 200, or 250 mg/d; n = 15) or 21 days (125, 200, 250, or 300 mg/d; n = 14) of each 21-day cycle. Dose escalation decisions were informed by continual reassessment methodology. Results Lymphocytosis was reduced by more than 50% in 19 of 21 patients with baseline lymphocytosis. Among 26 patients treated with navitoclax ≥ 110 mg/d, nine (35%) achieved a partial response and seven maintained stable disease for more than 6 months. Median treatment duration was 7 months (range, 1 to ≥ 29 months). Median progression-free survival was 25 months. Activity was observed in patients with fludarabine-refractory disease, bulky adenopathy, and del(17p) CLL. Thrombocytopenia due to BCL-xl inhibition was the major dose-limiting toxicity and was dose-related. Low MCL1 expression and high BIM:MCL1 or BIM:BCL2 ratios in leukemic cells correlated with response. We determined that the navitoclax dose of 250 mg/d in a continuous dosing schedule was optimal for phase II studies. Conclusion BCL2 is a valid therapeutic target in CLL, and its inhibition by navitoclax warrants further evaluation as monotherapy and in combination in this disease. PMID:22184378

  19. Decreased sensitivity to paroxetine-induced inhibition of peripheral blood mononuclear cell growth in depressed and antidepressant treatment-resistant patients.

    PubMed

    Rzezniczek, S; Obuchowicz, M; Datka, W; Siwek, M; Dudek, D; Kmiotek, K; Oved, K; Shomron, N; Gurwitz, D; Pilc, A

    2016-01-01

    Major depression disorder (MDD) is the most widespread mental disorder. Selective serotonin reuptake inhibitors (SSRIs) are used as first-line MDD treatment but are effective in <70% of patients. Thus, biomarkers for the early identification of treatment-resistant (TR) MDD patients are needed for prioritizing them for alternative therapeutics. SSRI-induced inhibition of the growth of peripheral blood mononuclear cells (PBMCs) is mediated via their target, the serotonin transporter (SERT). Here, we examined whether antidepressant drug-induced inhibition of the growth of PBMCs differed between MDD patients and healthy controls. PBMCs from well-characterized 33 treatment-sensitive (TS) and 33 TR MDD patients, and 24 healthy volunteers were studied. Dose-dependent inhibition of PBMCs growth was observed for both the non-SSRI antidepressant mirtazapine and the SSRI antidepressant paroxetine. Significantly lower sensitivities to 20 μm paroxetine were observed in MDD compared with control PBMCs prior to treatment onset (13% and 46%, respectively; P<0.05). Following antidepressant drug treatment for 4 or 7 weeks, the ex vivo paroxetine sensitivity increased to control levels in PBMCs from TS but not from TR MDD patients. This suggests that the low ex vivo paroxetine sensitivity phenotype reflects a state marker of depression. A significantly lower expression of integrin beta-3 (ITGB3), a co-factor of the SERT, was observed in the PBMCs of MDD patients prior to treatment onset compared with healthy controls, and may explain their lower paroxetine sensitivity. Further studies with larger cohorts are required for clarifying the potential of reduced PBMCs paroxetine sensitivity and lower ITGB3 expression as MDD biomarkers. PMID:27244236

  20. Dual antiangiogenic inhibition: a phase I dose escalation and expansion trial targeting VEGF-A and VEGFR in patients with advanced solid tumors

    PubMed Central

    Wheler, Jennifer J.; Naing, Aung; Piha-Paul, Sarina A.; Fu, Siqing; Tsimberidou, Apostolia M.; Hong, David S.; Janku, Filip; Zinner, Ralph; Jiang, Yunfang; Huang, Mei; Lin, Quan; Parkhurst, Kristin; Kurzrock, Razelle

    2015-01-01

    Summary Purpose Angiogenesis plays a pivotal role in tumor growth and metastasis. Sorafenib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR), combined with bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF-A), would vertically inhibit VEGF/VEGFR signaling. A phase I trial was performed to assess safety, maximum tolerated dose (MTD), and clinical correlates. Experimental design Patients with advanced solid tumors refractory to standard therapy were eligible. In cohorts of escalating doses, patients received sorafenib daily for 28 days and bevacizumab every two weeks. Clinical correlates included VEGF polymorphisms. Expansion cohorts of responding tumor types were enrolled. Results One hundred fifteen patients were treated, and the MTD was identified as 200 mg twice daily sorafenib and 5 mg/kg bevacizumab every two weeks. Median number of prior therapies was four. Twenty-nine patients (25 %) achieved stable disease ≥6 months; six patients (5 %) achieved a partial response (total SD≥6 months/PR=35 (30 %)). 76 patients (66 %) experienced adverse events of grade 2 or higher, most commonly hand and foot syndrome (n=27, 24 %) and hypertension (n=24, 21 %). Dose-limiting toxicity occurred in eight patients (7 %), and 45 patients (39 %) required dose reduction for toxicity. Grade 3 and 4 hypertension was associated with longer time to treatment failure, overall survival, and higher response rate. Conclusions Combination sorafenib and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with advanced solid tumors. PMID:25363205

  1. Assessment of asthmatic inflammation using hybrid fluorescence molecular tomography-x-ray computed tomography

    NASA Astrophysics Data System (ADS)

    Ma, Xiaopeng; Prakash, Jaya; Ruscitti, Francesca; Glasl, Sarah; Stellari, Fabio Franco; Villetti, Gino; Ntziachristos, Vasilis

    2016-01-01

    Nuclear imaging plays a critical role in asthma research but is limited in its readings of biology due to the short-lived signals of radio-isotopes. We employed hybrid fluorescence molecular tomography (FMT) and x-ray computed tomography (XCT) for the assessment of asthmatic inflammation based on resolving cathepsin activity and matrix metalloproteinase activity in dust mite, ragweed, and Aspergillus species-challenged mice. The reconstructed multimodal fluorescence distribution showed good correspondence with ex vivo cryosection images and histological images, confirming FMT-XCT as an interesting alternative for asthma research.

  2. Repeated Nitrogen Dioxide Exposures and Eosinophilic Airway Inflammation in Asthmatics: A Randomized Crossover Study

    PubMed Central

    Guillossou, Gaëlle; Neukirch, Catherine; Dehoux, Monique; Koscielny, Serge; Bonay, Marcel; Cabanes, Pierre-André; Samet, Jonathan M.; Mure, Patrick; Ropert, Luc; Tokarek, Sandra; Lambrozo, Jacques; Aubier, Michel

    2014-01-01

    Background: Nitrogen dioxide (NO2), a ubiquitous atmospheric pollutant, may enhance the asthmatic response to allergens through eosinophilic activation in the airways. However, the effect of NO2 on inflammation without allergen exposure is poorly studied. Objectives: We investigated whether repeated peaks of NO2, at various realistic concentrations, induce changes in airway inflammation in asthmatics. Methods: Nineteen nonsmokers with asthma were exposed at rest in a double-blind, crossover study, in randomized order, to 200 ppb NO2, 600 ppb NO2, or clean air once for 30 min on day 1 and twice for 30 min on day 2. The three series of exposures were separated by 2 weeks. The inflammatory response in sputum was measured 6 hr (day 1), 32 hr (day 2), and 48 hr (day 3) after the first exposure, and compared with baseline values measured twice 10–30 days before the first exposure. Results: Compared with baseline measurements, the percentage of eosinophils in sputum increased by 57% after exposure to 600 ppb NO2 (p = 0.003) but did not change significantly after exposure to 200 ppb. The slope of the association between the percentage of eosinophils and NO2 exposure level was significant (p = 0.04). Eosinophil cationic protein in sputum was highly correlated with eosinophil count and increased significantly after exposure to 600 ppb NO2 (p = 0.001). Lung function, which was assessed daily, was not affected by NO2 exposure. Conclusions: We observed that repeated peak exposures of NO2 performed without allergen exposure were associated with airway eosinophilic inflammation in asthmatics in a dose-related manner. Citation: Ezratty V, Guillossou G, Neukirch C, Dehoux M, Koscielny S, Bonay M, Cabanes PA, Samet JM, Mure P, Ropert L, Tokarek S, Lambrozo J, Aubier M. 2014. Repeated nitrogen dioxide exposures and eosinophilic airway inflammation in asthmatics: a randomized crossover study. Environ Health Perspect 122:850–855; http://dx.doi.org/10.1289/ehp.1307240 PMID

  3. Asthma knowledge and behaviours among mothers of asthmatic children in Aseer, south-west Saudi Arabia.

    PubMed

    Al-Binali, A M; Mahfouz, A A; Al-Fifi, S; Naser, S M; Al-Gelban, K S

    2010-11-01

    Mothers of children with bronchial asthma consecutively admitted to Aseer central hospital, Saudi Arabia (n = 171), were interviewed using a questionnaire based on the Chicago Community Asthma Survey to study their knowledge and behaviours concerning bronchial asthma. The least known information among mothers was the complications of bronchial asthma. Breathing exercises during asthma attacks were the least practised behaviour. In a multivariate analysis, significant risk factors for poor knowledge and behaviours among mothers were female sex of the child, illiterate mother and young age of mother (< 30 years). More education is needed to help the mothers of asthmatic children to acquire the necessary knowledge and practices to care for their children. PMID:21218739

  4. Exercise Leukocyte Profiles in Healthy, Type 1 Diabetic, Overweight, and Asthmatic Children

    PubMed Central

    2011-01-01

    Leukocytosis contributes to exercise-induced immune modulation, which is a mechanism of cardiovascular protection. However, this process is poorly defined in children. We therefore measured leukocytes in 45 healthy, 18 overweight, 16 type 1 diabetic, and 8 asthmatic children at pre-, end-, and 30-min post-exercise (30-min intermittent or 6-min continuous). In all groups, total leukocytes, neutrophils, lymphocytes, and monocytes increased at end-exercise, but returned to baseline by 30-min post-exercise, including neutrophils, previously reported to remain elevated for at least some exercise formats. This highly preserved pattern indicates the importance of the adaptive response to physical stress across multiple health conditions. PMID:19411708

  5. Fish oil supplementation decreases oxidative stress but does not affect platelet-activating factor bioactivity in lungs of asthmatic rats.

    PubMed

    Zanatta, A L; Miranda, D T S Z; Dias, B C L; Campos, R M; Massaro, M C; Michelotto, P V; West, A L; Miles, E A; Calder, P C; Nishiyama, A

    2014-07-01

    Dietary fish oil supplementation increases the content of n-3 polyunsaturated fatty acids (PUFA) in cellular membranes. The highly unsaturated nature of n-3 PUFA could result in an enhanced lipid peroxidation in the oxidative environment characteristic of asthma. The oxidative reaction cascade culminates in an increased production of components associated to oxidative stress and of an important proinflammatory mediator platelet-activating factor (PAF)-like lipid. We evaluated the effect of fish oil supplementation in asthmatic rats upon the PAF bioactivity and parameters related to oxidative stress in the lung. Fish oil supplementation of asthmatic rats resulted in lower concentrations of nitrite (1.719 ± 0.137 vs. 2.454 ± 0.163 nmol/mL) and lipid hydroperoxide (72.190 ± 7.327 vs. 120.200 ± 11.270 nmol/mg protein). In asthmatic animals, fish oil increased the activities of superoxide dismutase (EC 1.15.1.1) (33.910 ± 2.325 vs. 24.110 ± 0.618 U/mg protein) and glutathione peroxidase (EC 1.11.1.9) (164.100 ± 31.250 vs. 12.590 ± 5.234 U/mg protein). However, fish oil did not affect PAF bioactivity in lung tissue of asthmatic rats (0.545 ± 0.098 340/380 vs. 0.669 ± 0.101 340/380 nm ratio). Considering the two-step process--oxidative stress and PAF bioactivity--fish oil exhibited a divergent action on these aspects of asthmatic inflammation, since the supplement lowered oxidative stress in the lungs of asthmatic rats, presenting an antioxidant effect, but did not affect PAF bioactivity. This suggests a dual effect of fish oil on oxidative stress and inflammation in asthma. PMID:24858941

  6. Descriptors and Perception of Dyspnea in African-American Asthmatics

    PubMed Central

    Trochtenberg, D. Scott; BeLue, Rhonda

    2010-01-01

    Objective This study explores self-reported perception of asthma symptoms in African-Americans. Methods Qualitative methodology was used to analyze the responses from African-Americans within focus groups from Nashville, Tennessee. Results Common symptoms were chest tightness, “breathing problems,” and wheeze. Less commonly reported symptoms included cough, chest pain, dizziness, sweating, and “short of breath.” A single participant reported nocturnal wheezing. Conclusions This study provides insight into the descriptors and perception of asthma symptoms in African-Americans. Understanding the descriptors of symptoms and disease severity in African-American patients may lead to more accurate diagnosis, treatment, and reduced mortality within this high-risk population. PMID:18097855

  7. Genome-Wide Gene by Environment Interaction Analysis Identifies Common SNPs at 17q21.2 that Are Associated with Increased Body Mass Index Only among Asthmatics

    PubMed Central

    Wang, Leyao; Murk, William; DeWan, Andrew T.

    2015-01-01

    Asthmatics have an increased risk of being overweight/obese. Although the underlying mechanisms of this are unclear, genetic factors are believed to play an essential role. To identify common genetic variants that are associated with asthma-related BMI increase, we performed a genome-wide gene by environment (asthma) interaction analysis for the outcome of BMI in the Multi-Ethnic Study of Atherosclerosis (MESA) study (N = 2474 Caucasians, 257 asthmatics), and replicated findings in the Framingham Heart Study (FHS) offspring cohort (N = 1408 Caucasians, 382 asthmatics). The replicable tagging SNP, rs2107212, was further examined in stratified analyses. Seven SNPs clustered in 17q21.2 were identified to be associated with higher BMI among asthmatics (interaction p < 5×10−7 in MESA and p < 0.05 in FHS). In both MESA and FHS asthmatics, subjects carrying the A allele on rs2107212 had significantly higher odds of obesity than non-carriers, which was not the case for non-asthmatics. We further examined BMI change subsequent to asthma diagnosis over a period of 26 years in FHS and demonstrated greater BMI increase among asthmatics compared to non-asthmatics. Asthmatics carrying the A allele at rs2107212 had significantly greater net BMI increase over the 26-year period compared to non-asthmatics. In this study, we found that common genetic variants on 17q21.2 are associated with post-asthma BMI increase among Caucasians. This finding will help elucidate pathways involved in the comorbidity of asthma and obesity. PMID:26672748

  8. [An introduction to literature on infantile asthmatic coughing in the period of Sui - Tang to Song dynasties].

    PubMed

    Wan, F; Liu, Y

    2000-07-01

    Records in Zhu bing yuan hou lun are the primary accumulation of materials on infantile asthmatic coughing. The material from Bei ji qian jin yao fang and Qian jin yi fang were based on the author's life - long practical experience and applied by later generations. The guideline based on differential diagnosis of zheng for treating this ailment was established by Xiao er yao zheng zhi jue. While You you xin shu contains the most rich and detailed materials for this ailment before the Song dynasty, which, exerting profound influence on later generations in this field, is a milestone in the history of academic development of infantile asthmatic coughing. PMID:11624690

  9. P2Y12 receptor inhibition and effect of morphine in patients undergoing primary PCI for ST-segment elevation myocardial infarction. The PRIVATE-ATLANTIC study.

    PubMed

    Silvain, Johanne; Storey, Robert F; Cayla, Guillaume; Esteve, Jean-Baptiste; Dillinger, Jean-Guillaume; Rousseau, Hélène; Tsatsaris, Anne; Baradat, Caroline; Salhi, Néjoua; Hamm, Christian W; Lapostolle, Frédéric; Lassen, Jens Flensted; Collet, Jean-Philippe; Ten Berg, Jurriën M; Van't Hof, Arnoud W; Montalescot, Gilles

    2016-08-01

    PRIVATE-ATLANTIC (P2Y12 Receptor Inhibition with VASP Testing using Elisa kit during the ATLANTIC study) is a pre-specified substudy of the randomised, double-blind ATLANTIC trial in patients with ST-segment elevation myocardial infarction, designed to help interpret the main trial results. The primary objective of ATLANTIC was to assess coronary reperfusion prior to percutaneous coronary intervention (PCI) with pre- vs in-hospital ticagrelor 180 mg loading dose (LD). PRIVATE-ATLANTIC assessed platelet inhibition in 37 patients by measurement of vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) and VerifyNow platelet reactivity units (PRU) before angiogram (T1), immediately after PCI (T2), 1 (T3), and 6 (T4) hours (h) after PCI, and before next study drug administration (T5). The median time difference between the two ticagrelor LD was 41 minutes. Platelet reactivity was unaffected at T1 when measured by VASP-PRI (89.8 vs 93.9 % for pre- and in-hospital ticagrelor, respectively; p = 0.18) or PRU (239 vs 241; p = 0.82). Numerical differences were apparent at T2 and maximal at T3. Morphine administration significantly delayed onset of platelet inhibition at T3 (VASP-PRI 78.2 vs 23.4 % without morphine; p = 0.0116) and T4 (33.1 vs 11.0 %; p = 0.0057). In conclusion, platelet inhibition in ATLANTIC was unaffected by pre-hospital ticagrelor administration at the time of initial angiogram due to the short transfer delay. The maximum difference in platelet inhibition was detected 1 h after PCI (T3). Morphine administration was associated with delayed onset of action of ticagrelor and appeared more important than timing of ticagrelor administration. PMID:27196998

  10. Anaesthetic management of an asthmatic child for appendicectomy.

    PubMed

    Kuwahara, B; Goresky, G V

    1994-06-01

    A 13-yr-old boy was scheduled for emergency appendicectomy because of abdominal pain. His preoperative medical history was complicated by a recent hospital admission for management of asthma. He had presented to hospital seven days earlier because of dyspnoea, tachypnoea and oxygen desaturation to 77% on room air. Following admission, he required intensive nonventilatory management of his asthma, including intravenous salbutamol, methylprednisolone, and aminophylline, as well as use of an ipratroprium bromide inhaler and 100% oxygen by mask. He was discharged to the ward, and continued on prednisone (delta-cortisone), beclomethasone inhaler, ipratroprium inhaler, and salbutamol inhaler. During his ICU stay, he complained of nonspecific abdominal pain, interpreted as gastro-oesophageal reflux. After four days, he was discharged to the ward. On his sixth hospital day, he began to experience right-sided lower abdominal pain and right shoulder pain. A surgeon was consulted, and the patient was found to have a very tender right lower quadrant with guarding and rebound pain. He was therefore scheduled for appendicectomy; antibiotic therapy with ampicillin, gentamicin, and metronidazole was initiated. PMID:8069995

  11. Effect of Formaldehyde on Asthmatic Response to Inhaled Allergen Challenge

    PubMed Central

    Ezratty, Véronique; Bonay, Marcel; Neukirch, Catherine; Orset-Guillossou, Gaëlle; Dehoux, Monique; Koscielny, Serge; Cabanes, Pierre-André; Lambrozo, Jacques; Aubier, Michel

    2007-01-01

    Background Exposure to formaldehyde may lead to exacerbation of asthma. Objectives Our aim in this study was to investigate whether exposure to a low level (500 μg/m3) of formaldehyde enhances inhaled allergen responses. Methods Twelve subjects with intermittent asthma and allergy to pollen were exposed, at rest, in a double-blind crossover study to either formaldehyde or purified air for 60 min. The order of exposure to formaldehyde and air-only was randomized, and exposures were separated by 2 weeks. We also performed an allergen inhalation challenge after each exposure. Airway responsiveness to methacholine and lower airway inflammation (induced sputum) were assessed 8 hr after allergen challenge. Results The median dose of allergen producing a 15% decrease in forced expiratory volume in 1 sec (PD15FEV1) was 0.80 IR (index of reactivity) after formaldehyde exposure compared with 0.25 IR after air-only exposure (p = 0.06). Formaldehyde exposure did not affect allergen-induced increase in responsiveness to methacholine (p = 0.42). We found no formaldehyde-associated effect on the airway inflammatory response, in particular the eosinophilic inflammatory response, induced by the allergen challenge 8 hr before. Conclusion In this study, exposure to 500 μg/m3 formaldehyde had no significant deleterious effect on airway allergen responsiveness of patients with intermittent asthma; we found a trend toward a protective effect. PMID:17384766

  12. Effect of nitrous acid on lung function in asthmatics: a chamber study.

    PubMed Central

    Beckett, W S; Russi, M B; Haber, A D; Rivkin, R M; Sullivan, J R; Tameroglu, Z; Mohsenin, V; Leaderer, B P

    1995-01-01

    Nitrous acid, a component of photochemical smog and a common indoor air pollutant, may reach levels of 100 ppb where gas stoves and unvented portable kerosene heaters are used. Nitrous acid is a primary product of combustion and may also be a secondary product by reaction of nitrogen dioxide with water. Because the usual assays for nitrogen dioxide measure several oxides of nitrogen (including nitrous acid) together, previous studies of indoor nitrogen dioxide may have included exposure to and health effects of nitrous acid. To assess the respiratory effects of nitrous acid exposure alone, we carried out a double-blinded crossover chamber exposure study with 11 mildly asthmatic adult subjects. Each underwent 3-hr exposures to 650 ppb nitrous acid and to filtered room air with three 20-min periods of moderate cycle exercise. Symptoms, respiratory parameters during exercise, and spirometry after exercise were measured. A statistically significant decrease in forced vital capacity was seen on days when subjects were exposed to nitrous acid. This effect was most marked at 25 min and 85 min after exposure began. Aggregate respiratory and mucous membrane symptoms were also significantly higher with nitrous acid. We conclude that this concentration and duration of exposure to nitrous acid alters lung mechanics slightly, does not induce significant airflow obstruction, and produces mild irritant symptoms in asthmatics. Images Figure 1. PMID:7607138

  13. Time course of exercise-induced bronchoconstriction in asthmatics exposed to sulfur dioxide

    SciTech Connect

    Hackney, J.D.; Linn, W.S.; Bailey, R.M.; Spier, C.E.; Valencia, L.M.

    1984-08-01

    Young adult asthmatic volunteers (N = 17) were exposed to 0.75 ppM sulfur dioxide (SO/sub 2/) for 3-hr periods, exercising vigorously for the first 10 min and resting thereafter. Specific airway resistance (SR/sub aw/) and symptoms were recorded preexposure, immediately postexercise, and after 1, 2, and 3 hr of exposure. Symptoms and SR/sub aw/ were significantly increased after exercise, relative to preexposure measurements. Group mean SR/sub aw/ and symptom increases were no longer significant at 1 hr. In a few individuals, effects may have persisted for 2 hr or more. On separate occasions, comparable exposures were conducted, and forced expiratory spirometry was performed preexposure and postexercise, in addition to the other tests. Inclusion of spirometry did no significantly affect the other results. Spirometry and SR/sub aw/ showed nearly equal significance in changes postexercise. Thus, in general, asthmatics bronchoconstriction induced by exercise in SO/sub 2/ seems to reverse quickly with rest, even if SO/sub 2/ exposure continues. Spirometry may be useful for studying pollution-induced bronchoconstriction when SR/sub aw/ measurements are impractical.

  14. Altered heart-rate variability in asthmatic and healthy volunteers exposed to concentrated ambient coarse particles.

    PubMed

    Gong, Henry; Linn, William S; Terrell, Sheryl L; Clark, Kenneth W; Geller, Michael D; Anderson, Karen R; Cascio, Wayne E; Sioutas, Constantinos

    2004-06-01

    Twelve mildly asthmatic and four healthy adults were exposed to filtered air (FA) and concentrated ambient coarse particles (CCP) supplied to a whole-body exposure chamber via a coarse particle concentrator with 15 parallel virtual impactors. Exposures were conducted in a Los Angeles suburb with high levels of motor-vehicle pollution and lasted 2 h with intermittent exercise. Mean CCP concentration was 157 microg/m(3) (range: 56-218 microg/m(3)) measured by continuous monitoring with a tapered-element oscillating microbalance (TEOM). On average, 80% of mass was coarse (2.5-10 microm aerodynamic diameter) and the rest <2.5 microm. Relative to FA, CCP exposure did not significantly alter respiratory symptoms, spirometry, arterial oxygen saturation, or airway inflammation according to exhaled nitric oxide and total and differential cell counts of induced sputum. After CCP exposure, Holter electrocardiograms showed small (p <.05) increases in heart rate and decreases in heart-rate variability, which were larger in healthy than in asthmatic subjects. Cardiac ectopy did not increase. In conclusion, acute exposure to elevated concentrations of ambient coarse particles elicited no obvious pulmonary effects but appeared to alter the autonomic nervous system of the heart in adult volunteers. PMID:15204749

  15. Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways

    PubMed Central

    Tränkner, Dimitri; Hahne, Nadeau; Sugino, Ken; Hoon, Mark A.; Zuker, Charles

    2014-01-01

    Asthma is a common debilitating inflammatory lung disease affecting over 200 million people worldwide. Here, we investigated neurogenic components involved in asthmatic-like attacks using the ovalbumin-sensitized murine model of the disease, and identified a specific population of neurons that are required for airway hyperreactivity. We show that ablating or genetically silencing these neurons abolished the hyperreactive broncho-constrictions, even in the presence of a fully developed lung inflammatory immune response. These neurons are found in the vagal ganglia and are characterized by the expression of the transient receptor potential vanilloid 1 (TRPV1) ion channel. However, the TRPV1 channel itself is not required for the asthmatic-like hyperreactive airway response. We also demonstrate that optogenetic stimulation of this population of TRP-expressing cells with channelrhodopsin dramatically exacerbates airway hyperreactivity of inflamed airways. Notably, these cells express the sphingosine-1-phosphate receptor 3 (S1PR3), and stimulation with a S1PR3 agonist efficiently induced broncho-constrictions, even in the absence of ovalbumin sensitization and inflammation. Our results show that the airway hyperreactivity phenotype can be physiologically dissociated from the immune component, and provide a platform for devising therapeutic approaches to asthma that target these pathways separately. PMID:25049382

  16. Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways.

    PubMed

    Tränkner, Dimitri; Hahne, Nadeau; Sugino, Ken; Hoon, Mark A; Zuker, Charles

    2014-08-01

    Asthma is a common debilitating inflammatory lung disease affecting over 200 million people worldwide. Here, we investigated neurogenic components involved in asthmatic-like attacks using the ovalbumin-sensitized murine model of the disease, and identified a specific population of neurons that are required for airway hyperreactivity. We show that ablating or genetically silencing these neurons abolished the hyperreactive broncho-constrictions, even in the presence of a fully developed lung inflammatory immune response. These neurons are found in the vagal ganglia and are characterized by the expression of the transient receptor potential vanilloid 1 (TRPV1) ion channel. However, the TRPV1 channel itself is not required for the asthmatic-like hyperreactive airway response. We also demonstrate that optogenetic stimulation of this population of TRP-expressing cells with channelrhodopsin dramatically exacerbates airway hyperreactivity of inflamed airways. Notably, these cells express the sphingosine-1-phosphate receptor 3 (S1PR3), and stimulation with a S1PR3 agonist efficiently induced broncho-constrictions, even in the absence of ovalbumin sensitization and inflammation. Our results show that the airway hyperreactivity phenotype can be physiologically dissociated from the immune component, and provide a platform for devising therapeutic approaches to asthma that target these pathways separately. PMID:25049382

  17. Respiratory responses of young adult asthmatics to sulfur dioxide exposure under simulated ambient conditions

    SciTech Connect

    Linn, W.S.; Bailey, R.M.; Shamoo, D.A.; Venet, T.G.; Wightman, L.H.; Hackney, J.D.

    1982-10-01

    Twenty-four young adult asthmatic volunteers were exposed to 0, 0.25, and 0.50 ppm SO/sub 2/ in random order at 1-week intervals. Exposures, conducted in a controlled-environment chamber at 23/sup 0/C and 90+% relative humidity, lasted 1 hr and incorporated alternating 10-min periods of moderate exercise (mean exercise ventilation about 27 liters/min) and rest. Airway resistance was measured before exposure, after the first exercise period, and near the end of exposure. Forced expiratory performance was measured after the final airway resistance measurement. Exposure-relatable symptoms were recorded before, during, and after exposure periods. None of these measures of response showed statistically significant variation attributable to SO/sub 2/, although small significant increases in resistance attributable to exercise were found. These negative results contrast with previous positive findings in asthmatics exposed to SO/sub 2/ via mouthpiece. The differences may relate to effects of mouthpiece breathing on respiratory defenses, or to interindividual variations in bronchial reactivity to SO/sub 2/.

  18. [Effect of fog on diurnal changes in peak expiratory flow rates in an asthmatic].

    PubMed

    Tanaka, H; Honma, S; Imada, A; Sugaya, F; Nishi, M; Abe, S

    1995-02-01

    To evaluate the effects of fog on asthmatics, we analyzed the symptoms of a 45-year-old female during the foggy season and the relation between diurnal peak expiratory flow rate (PEFR) and fog and other meteorological factors. Her asthma attacks had been induced by specific smells: perfume, smoke from burning grass or industrial smoke. Two years previously, she had moved to the suburbs of Sapporo, where fog frequently occurs. From that time her asthmatic symptoms had been exacerbated, so it was suspected that the fog might have had some influence. We analyzed 251 measures of PEFR from June to August 1994. The average and standard deviation of PEFR in the absence of fog and specific smells was 403 +/- 40 L/min (n = 195). PEFR was significantly lower (p < 0.01) when it was foggy (347 +/- 60 L/min; n = 40), when specific smells were present (333 +/- 60 L/min; n = 5) and when there were both fog and specific smells (340 +/- 53 L/min: n = 11). On the other hand, there were no changes associated with other meteorological factors: barometric pressures, relative humidity, mean temperature, minimal temperature and most frequent wind direction. These results suggested that the inhalation of fog decreases PEFR and is an exacerbating factor in bronchial asthma. PMID:7726750

  19. Controlled trial of a home and ambulatory program for asthmatic children.

    PubMed

    Hughes, D M; McLeod, M; Garner, B; Goldbloom, R B

    1991-01-01

    Care of asthmatic children is often episodic and more therapeutic than preventive. A 2-year randomized, controlled trial involving 95 children measured the impact of a comprehensive home and ambulatory program for pediatric asthma management using objective outcome measures. Interventions for the study group during the first year included 3-month clinic visits, education, and home visits by a specially trained research nurse. Control subjects continued to receive regular care from a family physician or pediatrician. Eight-nine subjects (93%) completed the study. Study subjects had less school absenteeism than control subjects (10.7 vs. 16.0 days, P = .04) and showed significantly better small airway function after 1 year. Asthma severity improved in 13 study subjects and worsened in 5. The reverse was true for control subjects. Study subjects exhibited better metered aerosol technique than control subjects (P = .0005). Fewer days were spent in hospital by the study subjects admitted compared with control subjects (3.67 vs 11.2 days, P = .02). After 1 year, more study than control families (72.1% vs 33.1%, P = .006) reported that their asthmatic child took responsibility for the asthma management. The intervention failed to reduce exposure to secondhand smoke or to household pets. There were no significant differences in medical visits, theophylline levels, or records of asthma symptoms. One year after discontinuing the intervention, a marked "washout" effect was observed. Comprehensive ambulatory programs of childhood asthma management can improve objective measures of illness severity but must be sustained. PMID:1984619

  20. A MYLK variant regulates asthmatic inflammation via alterations in mRNA secondary structure.

    PubMed

    Wang, Ting; Zhou, Tong; Saadat, Laleh; Garcia, Joe G N

    2015-06-01

    Myosin light-chain kinase (MYLK) is a gene known to be significantly associated with severe asthma in African Americans. Here we further examine the molecular function of a single-nucleotide polymorphism (SNP), located in the non-muscle myosin light-chain kinase isoform (nmMLCK), in asthma susceptibility and pathobiology. We identified nmMLCK variant (reference SNP: rs9840993, NM_053025: 721C>T, c.439C>T) with a distinct mRNA secondary structure from the other variants. The nmMLCK variant (721C) secondary structure exhibits increased stability with an elongated half-life in the human endothelial cell, and greater efficiency in protein translation initiation owing to an increased accessibility to translation start site. Finally, nmMLCK expression of 721C- and 721T-containing MYLK transgenes were compared in nmMLCK(-/-) mice and confirmed deleterious effects of nmMLCK expression on asthmatic indices and implicated the augmented influence of MYLK 721C>T (c.439C>T) SNP on asthma severity. The confirmation of the novel mechanism of the regulation of asthmatic inflammation by a MYLK advances knowledge of the genetic basis for asthma disparities, and further suggests the potential of nmMLCK as a therapeutic target. Our study suggests that in addition to altering protein structure and function, non-synonymous SNPs may also lead to phenotypic disparity by altering protein expression. PMID:25271083

  1. Effect of metaproterenol sulfate on mild asthmatics' response to sulfur dioxide exposure and exercise

    SciTech Connect

    Linn, W.S.; Avol, E.L.; Shamoo, D.A.; Peng, R.C.; Spier, C.E.; Smith, M.N.; Hackney, J.D.

    1988-11-01

    Twenty asthmatic volunteers, most with mild disease, underwent dose-response studies with sulfur dioxide (SO2) under three pretreatment conditions: (1) drug (metaproterenol sulfate in aerosolized saline solution), (2) placebo (aerosolized saline only), and (3) no pretreatment. Sulfur dioxide exposure concentrations were 0.0, 0.3, and 0.6 ppm. Experimental conditions were presented in random order at 1-wk intervals. Exposures lasted 10 min with heavy continuous exercise. Lung function was measured at baseline, after pretreatment (immediately pre-exposure), immediately post-exposure, and during a 2-hr follow-up. Subjects could elect to take bronchodilators during follow-up. Symptoms were monitored before, during, and for 1 wk after exposure. With no pretreatment, subjects exhibited typical exercise-induced bronchospasm at 0.0 ppm, slightly increased responses at 0.3 ppm, and more marked increases at 0.6 ppm. Seven subjects took bronchodilator after 0.6-ppm exposures, compared to 2 at lower concentrations. Within 30 min post-exposure, most subjects' symptoms and lung function had returned to near pre-exposure levels. A similar sequence was observed when subjects received placebo. Drug pretreatment improved lung function relative to baseline, prevented bronchoconstrictive responses at 0.0 and 0.3 ppm, and greatly mitigated responses at 0.6 ppm. Thus, typical bronchodilator usage by asthmatics is likely to reduce their response to ambient SO2 pollution.

  2. Berberine potently attenuates intestinal polyps growth in ApcMin mice and familial adenomatous polyposis patients through inhibition of Wnt signalling

    PubMed Central

    Zhang, Junfang; Cao, Hailong; Zhang, Bing; Cao, Hanwei; Xu, Xiuqin; Ruan, Hang; Yi, Tingting; Tan, Li; Qu, Rui; Song, Gang; Wang, Bangmao; Hu, Tianhui

    2013-01-01

    As a traditional anti-inflammatory Chinese herbal medicine, Alkaloid berberine has been recently reported to exhibit anti-tumour effects against a wide spectrum of cancer. However, the mechanism was largely unknown. Gene chip array reveals that with berberine treatment, c-Myc, the target gene of Wnt pathway, was down-regulated 5.3-folds, indicating that berberine might inhibit Wnt signalling. TOPflash analysis revealed that Wnt activity was significantly reduced after berberine treatment, and the mechanism of which might be that berberine disrupted β-catenin transfer to nucleus through up-regulating the expression of adenomatous polyposis coli (APC) gene and stabilized APC-β-catenin complex. Berberine administration in ApcMin/+ mice exhibited fewer and smaller polyps in intestine, along with reduction in cyclin D1 and c-Myc expression. In clinical practice, oral administration of berberine also significantly reduced the familial adenomatous polyposis patients' polyp size along with the inhibition of cyclin D1 expression in polyp samples. These observations indicate that berberine inhibits colon tumour formation through inhibition of Wnt/β-catenin signalling and berberine might be a promising drug for the prevention of colon cancer. PMID:24015932

  3. The neural substrates of response inhibition to negative information across explicit and implicit tasks in GAD patients: electrophysiological evidence from an ERP study

    PubMed Central

    Yu, Fengqiong; Zhu, Chunyan; Zhang, Lei; Chen, Xingui; Li, Dan; Zhang, Long; Ye, Rong; Dong, Yi; Luo, Yuejia; Hu, Xinlong; Wang, Kai

    2015-01-01

    Background: It has been established that the inability to inhibit a response to negative stimuli is the genesis of anxiety. However, the neural substrates of response inhibition to sad faces across explicit and implicit tasks in general anxiety disorder (GAD) patients remain unclear. Methods: Electrophysiological data were recorded when subjects performed two modified emotional go/no-go tasks in which neutral and sad faces were presented: one task was explicit (emotion categorization), and the other task was implicit (gender categorization). Results: In the explicit task, electrophysiological evidence showed decreased amplitudes of no-go/go difference waves at the N2 interval in the GAD group compared to the control group. However, in the implicit task, the amplitudes of no-go/go difference waves at the N2 interval showed a reversed trend. Source localization analysis on no-go/N2 components revealed a decreased current source density (CSD) in the right dorsal lateral prefrontal cortex in GAD individuals relative to controls. In the implicit task, the left superior temporal gyrus and the left inferior parietal lobe showed enhanced activation in GAD individuals and may compensate for the dysfunction of the right dorsal lateral prefrontal cortex. Conclusion: These findings indicated that the processing of response inhibition to socially sad faces in GAD individuals was interrupted in the explicit task. However, this processing was preserved in the implicit task. The neural substrates of response inhibition to sad faces were dissociated between implicit and explicit tasks. PMID:25852597

  4. Inhibition of Major Drug Metabolizing CYPs by Common Herbal Medicines used by HIV/AIDS Patients in Africa– Implications for Herb-Drug Interactions

    PubMed Central

    Awortwe, Charles; Bouic, Patrick J.; Masimirembwa, Collen M.; Rosenkranz, Bernd

    2015-01-01

    The purpose of this study was to evaluate the potential risk of common herbal medicines used by HIV-infected patients in Africa for herb-drug interactions (HDI). High throughput screening assays consisting of recombinant Cytochrome P450 enzymes (CYPs) and fluorescent probes, and parallel artificial membrane permeability assays (PAMPA) were used. The potential of herbal medicines to cause HDI was ranked according to FDA guidelines for reversible inhibition and categorization of time dependent inhibition was based on the normalized ratio. CYPs 1A2 and 3A4 were most inhibited by the herbal extracts. H. hemerocallidea (IC50 = 0.63 μg/mL and 58 μg/mL) and E. purpurea (IC50 = 20 μg/mL and 12 μg/mL) were the potent inhibitors of CYPs 1A2 and 3A4 respectively. L. frutescens and H. hemerocallidea showed clear time dependent inhibition on CYP3A4. Furthermore, the inhibitory effect of both H. hemerocallidea and L. frutescens before and after PAMPA were identical. The results indicate potential HDI of H. hemerocallidea, L. frutescens and E. purpurea with substrates of the affected enzymes if maximum in vivo concentration is achieved. PMID:24475926

  5. Effects of TGF-beta signalling inhibition with galunisertib (LY2157299) in hepatocellular carcinoma models and in ex vivo whole tumor tissue samples from patients.

    PubMed

    Serova, Maria; Tijeras-Raballand, Annemilaï; Dos Santos, Célia; Albuquerque, Miguel; Paradis, Valerie; Neuzillet, Cindy; Benhadji, Karim A; Raymond, Eric; Faivre, Sandrine; de Gramont, Armand

    2015-08-28

    Galunisertib (LY2157299) is a selective ATP-mimetic inhibitor of TGF-β receptor (TβR)-I activation currently under clinical investigation in hepatocellular carcinoma (HCC) patients. Our study explored the effects of galunisertib in vitro in HCC cell lines and ex vivo on patient samples. Galunisertib was evaluated in HepG2, Hep3B, Huh7, JHH6 and SK-HEP1 cells as well as in SK-HEP1-derived cells tolerant to sorafenib (SK-Sora) and sunitinib (SK-Suni). Exogenous stimulation of all HCC cell lines with TGF-β yielded downstream activation of p-Smad2 and p-Smad3 that was potently inhibited with galunisertib treatment at micromolar concentrations. Despite limited antiproliferative effects, galunisertib yielded potent anti-invasive properties. Tumor slices from 13 patients with HCC surgically resected were exposed ex vivo to 1 µM and 10 µM galunisertib, 5 µM sorafenib or a combination of both drugs for 48 hours. Galunisertib but not sorafenib decreased p-Smad2/3 downstream TGF-β signaling. Immunohistochemistry analysis of galunisertib and sorafenib-exposed samples showed a significant decrease of the proliferative marker Ki67 and increase of the apoptotic marker caspase-3. In combination, galunisertib potentiated the effect of sorafenib efficiently by inhibiting proliferation and increasing apoptosis. Our data suggest that galunisertib may be active in patients with HCC and could potentiate the effects of sorafenib. PMID:26057634

  6. Effects of TGF-beta signalling inhibition with galunisertib (LY2157299) in hepatocellular carcinoma models and in ex vivo whole tumor tissue samples from patients

    PubMed Central

    Serova, Maria; Tijeras-Raballand, Annemilaï; Santos, Célia Dos; Albuquerque, Miguel; Paradis, Valerie; Neuzillet, Cindy; Benhadji, Karim A.; Raymond, Eric; Faivre, Sandrine; de Gramont, Armand

    2015-01-01

    Galunisertib (LY2157299) is a selective ATP-mimetic inhibitor of TGF-β receptor (TβR)-I activation currently under clinical investigation in hepatocellular carcinoma (HCC) patients. Our study explored the effects of galunisertib in vitro in HCC cell lines and ex vivo on patient samples. Galunisertib was evaluated in HepG2, Hep3B, Huh7, JHH6 and SK-HEP1 cells as well as in SK-HEP1-derived cells tolerant to sorafenib (SK-Sora) and sunitinib (SK-Suni). Exogenous stimulation of all HCC cell lines with TGF-β yielded downstream activation of p-Smad2 and p-Smad3 that was potently inhibited with galunisertib treatment at micromolar concentrations. Despite limited antiproliferative effects, galunisertib yielded potent anti-invasive properties. Tumor slices from 13 patients with HCC surgically resected were exposed ex vivo to 1 μM and 10 μM galunisertib, 5 μM sorafenib or a combination of both drugs for 48 hours. Galunisertib but not sorafenib decreased p-Smad2/3 downstream TGF-β signaling. Immunohistochemistry analysis of galunisertib and sorafenib-exposed samples showed a significant decrease of the proliferative marker Ki67 and increase of the apoptotic marker caspase-3. In combination, galunisertib potentiated the effect of sorafenib efficiently by inhibiting proliferation and increasing apoptosis. Our data suggest that galunisertib may be active in patients with HCC and could potentiate the effects of sorafenib. PMID:26057634

  7. Diagnostic value and influencing factors of fractional exhaled nitric oxide in suspected asthma patients

    PubMed Central

    Wang, Yubo; Li, Li; Han, Rui; Lei, Wenhui; Li, Zhongyan; Li, Kunlin; Kang, Jun; Chen, Hengyi; He, Yong

    2015-01-01

    Objective: To explore the critical value and possible influencing factors of fractional exhaled nitric oxide (FeNO) in suspected asthma patients. Methods: 923 suspected asthmatics consecutively referred to our hospital during December 2012 to July 2014 were selected. All cases were carried out FeNO measurement at first; next, spirometry, bronchoprovocation tests or bronchodilation tests were used to confirm or exclude asthma. Receiver operating characteristic curve (ROC) was used to determine the best cut-off value of FeNO for asthma diagnosis. Results: In bronchoprovocation test, 125 cases were diagnosed as asthma, other 283 were non-asthmatics. FeNO levels of asthmatics were significantly higher than non-asthmatics (median, 64.8 ppb vs. 27.9 ppb, P < 0.01). In this group of patients, 64 ppb was the best cut-off value of FeNO to identify asthma with sensitivity of 52.0% and specificity of 94.35%. In bronchodilation test, 185 patients were diagnosed as asthma, other 330 were non-asthmatics. FeNO levels of asthmatics were significantly higher than non-asthmatics (median, 60.6 ppb vs. 29.05 ppb, P < 0.01). In bronchodilation test patients, 41 ppb was the best cut-off value of FeNO to identify asthma with sensitivity of 72.43% and specificity of 74.85%. Influencing factors analysis showed that sex was an independent factor affecting patients’ FeNO level. Conclusion: FeNO was an effective auxiliary diagnosis method for bronchial asthma. 64 ppb and 41 ppb was the best cut-off value of FeNO to identify asthma in bronchoprovocation test or bronchodilation test, respectively. Sex was an independent factor affecting patients’ FeNO level. PMID:26191266

  8. Modeling exposures to traffic-related air pollutants for the NEXUS respiratory health study of asthmatic children in Detroit, MI

    EPA Science Inventory

    The Near-Road EXposures and Effects of Urban Air Pollutants Study (NEXUS) was designed to investigate associations between exposure to traffic-related air pollution and the respiratory health of asthmatic children living near major roadways in Detroit, MI. A combination of modeli...

  9. Higher Environmental Relative Moldiness Index (ERMI) Values Measured in Homes of Asthmatic Children in Boston, Kansas City and San Diego

    EPA Science Inventory

    ABSTRACT Asthmatic children in Boston (n=76), Kansas City (n=60) and San Diego (n=93) were found to be living in homes with significantly higher Environmental Relative Moldiness Index (ERMI) values than were found in homes randomly selected during the HUD 2006 American Healthy H...

  10. SULFUR DIOXIDE-INDUCED BRONCHOCONSTRICTION IN ASTHMATICS EXPOSED FOR SHORT DURATIONS UNDER CONTROLLED CONDITIONS: A SELECTED REVIEW

    EPA Science Inventory

    Prior to 1980, essentially no health related effects had been observed for short-term ( < 1 hr) exposures to sulfur dioxide (SO2) levels similar to those found in the ambient environment (= or < 1 ppm). In 1980 and 81, the results from several studies indicated that asthmatics' a...

  11. Airway protease/antiprotease imbalance in atopic asthmatics contributes to increased influenza A virus cleavage and replication

    EPA Science Inventory

    Asthmatics are more susceptible to influenza infections, yet mechanisms mediating this enhanced susceptibility are unknown. Influenza virus hemagglutinin (HA) protein binds to sialic add residues on the host cells. HA requires cleavage to allow fusion of the viral HA with host ce...

  12. The preventive effect of Brassica napus L. oil on pathophysiological changes of respiratory system in experimental asthmatic rat

    PubMed Central

    Kabiri rad, Mehdi; Neamati, Ali; Boskabady, Mohammad Hossein; Mahdavi-Shahri, Naser; Mahmoudabady, Maryam

    2013-01-01

    Objective: Asthma is an airway complex disease defined by reversible airway narrowing and obstruction, chronic airway inflammation, airway hyperresponsiveness, and tissue remodeling. The purpose of this study was to determine the effect of Brassica napus L. (B. napus) on airway pathologic changes in a rat model of asthma. Materials and Methods: Twenty-four rats were divided into 4 groups: control, asthmatic, asthmatic treated with 0.5 mg/kg B. napus oil, and asthmatic treated with 0.75 mg/kg B. napus oil. To induce the experimental asthma, rats in groups 2, 3, and 4 received an i.p. injection of ovalbumin and aerosolized ovalbumin. Simultaneously, rats in groups 3 and 4 received B. napus oil daily by gavage. After 31 days, in all groups, thoracotomy was done and lung tissue samples were taken. For pathological evaluation, microscopic slides were prepared. The eosinophil numbers in the submucosal layer and thicknesses of smooth muscle layer of bronchioles were detected. Results: Eosinophil numbers in the submucosal layer, as well as smooth muscle layer thicknesses were significantly lower in the rat group treated with 0.75 mg/kg B. napus oil as compared with asthmatic group (p<0.01, p<0.05). Conclusion: B. napus could be useful as adjuvant therapy in rat model of asthma. This effect was probably related to its antioxidants components that reduce the levels of inflammatory mediators such as leukotrienes, IL-4, IL-5, and IL-13. PMID:25050259

  13. THE SHORT AND LONG-TERM RESPIRATORY EFFECTS OF EXPOSURE TO PAHS FROM TRAFFIC IN A COHORT OF ASTHMATIC CHILDREN

    EPA Science Inventory

    EPA GRANT NUMBER: R828678C017
    Title: The Short and Long-Term Respiratory Effects of Exposure to PAHs from Traffic in a Cohort of Asthmatic Children
    Investigator: S. Katharine Hammond
    Institution: University of California - Berkeley
    E...

  14. EFFECT OF INHALED ENDOTOXIN ON AIRWAY AND CIRCULATING INFLAMMATORY CELL PHAGOCYTOSIS AND CD11B EXPRESSION IN ATOPIC ASTHMATIC SUBJECTS

    EPA Science Inventory

    Effect of inhaled endotoxin on airway and circulating inflammatory cell phagocytosis and CD11b expression in atopic asthmatic subjects

    Neil E. Alexis, PhD, Marlowe W. Eldridge, MD, David B. Peden, MD, MS

    Chapel Hill and Research Triangle Park, NC

    Backgrou...

  15. Airway responsiveness to leukotriene C4 (LTC4), leukotriene E4 (LTE4) and histamine in aspirin-sensitive asthmatic subjects.

    PubMed

    Christie, P E; Schmitz-Schumann, M; Spur, B W; Lee, T H

    1993-11-01

    We wanted to determine whether the airway response to inhaled leukotriene C4 (LTC4) is similar to inhaled leukotriene E4 (LTE4) in aspirin-sensitive asthma and, therefore, determined airway responsiveness to histamine, LTC4 and LTE4 in seven aspirin-sensitive subjects and 13 control asthmatic subjects, who were tolerant of aspirin. The concentration of inhaled lysine-aspirin which produced a 15% fall in forced expiratory volume in one second (FEV1) (PC15) was determined in aspirin-sensitive asthmatic subjects. The dose of histamine, LTC4 and LTE4 which produced a 35% fall in specific airways conductance (PD35sGaw) was determined by linear interpolation from the log dose response curve. There was no correlation between the PC15 for lysine-aspirin and the airway reactivity to inhaled LTC4 or LTE4. There was no difference in airway response to histamine and LTC4 between any of the groups of asthmatic subjects. There was a rank order of potency LTC4 > LTE4 > histamine in both groups, with LTC4 approximately 1,000 fold more potent than histamine in both groups. Aspirin-sensitive asthmatic subjects were significantly more responsive to LTE4 (p = 0.02) than aspirin-tolerant asthmatic subjects. The relative responsiveness of LTE4 to histamine (PD35 histamine/PD35 LTE4) was significantly greater in aspirin-sensitive asthmatic subjects compared to aspirin-tolerant asthmatic subjects (p = 0.05). There was no difference in relative responsiveness of LTC4 to histamine between aspirin-sensitive or aspirin-tolerant asthmatic subjects. We conclude that the airways of aspirin-sensitive asthmatic subjects demonstrate a selective hyperresponsiveness to LTE4, which is not observed for LTC4. PMID:8112440

  16. Dual Effects of Cellular Immunotherapy in Inhibition of Virus Replication and Prolongation of Survival in HCV-Positive Hepatocellular Carcinoma Patients

    PubMed Central

    Wang, Nanya; Tian, Huimin; Jin, Haofan; Zhao, Hengjun; Niu, Chao; He, Hua; Ge, Tingwen; Han, Wei; Hu, Jifan; Li, Dan; Han, Fujun; Xu, Jianting; Ding, Xiao; Chen, Jingtao; Li, Wei; Cui, Jiuwei

    2016-01-01

    Immune cells play an important role in the development and progression of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC). We conducted a retrospective study to evaluate the influence of adoptive cellular immunotherapy (CIT) on viral load and progression-free survival (PFS) for HCC patients infected with HCV. Patients (n = 104) were divided into a control group (conventional therapy, n = 73) and study group (combination of CIT and conventional therapy, n = 31). Autologous mononuclear cells were induced into natural killer, γδT, and cytokine-induced killer cells and infused intravenously to study group patients. More patients had shown viral load decrease or were stable in study group (100% versus 75%) (p = 0.014). The median PFS of the study group and control group was 16 and 10 months, respectively (p = 0.0041), and only CIT was an independent prognostic factor for PFS (hazard ratio, 0.422; p = 0.005). Three patients developed transient moderate fever after infusion, and there were no significant differences in alanine aminotransferase and aspartate aminotransferase levels before and after treatment in both groups. Our results show that CIT contributes to improvement of prognosis and inhibition of viral replication in HCV-related HCC patients, without impairment of liver function. PMID:27069936

  17. Inhibition of prostaglandin synthesis and actions by genistein in human prostate cancer cells and by soy isoflavones in prostate cancer patients.

    PubMed

    Swami, Srilatha; Krishnan, Aruna V; Moreno, Jacqueline; Bhattacharyya, Rumi S; Gardner, Christopher; Brooks, James D; Peehl, Donna M; Feldman, David

    2009-05-01

    Soy and its constituent isoflavone genistein inhibit the development and progression of prostate cancer (PCa). Our study in both cultured cells and PCa patients reveals a novel pathway for the actions of genistein, namely the inhibition of the synthesis and biological actions of prostaglandins (PGs), known stimulators of PCa growth. In the cell culture experiments, genistein decreased cyclooxygenase-2 (COX-2) mRNA and protein expression in both human PCa cell lines (LNCaP and PC-3) and primary prostate epithelial cells and increased 15-hydroxyprostaglandin dehydrogenase (15-PGDH) mRNA levels in primary prostate cells. As a result genistein significantly reduced the secretion of PGE(2) by these cells. EP4 and FP PG receptor mRNA were also reduced by genistein, providing an additional mechanism for the suppression of PG biological effects. Further, the growth stimulatory effects of both exogenous PGs and endogenous PGs derived from precursor arachidonic acid were attenuated by genistein. We also performed a pilot randomised double blind clinical study in which placebo or soy isoflavone supplements were given to PCa patients in the neo-adjuvant setting for 2 weeks before prostatectomy. Gene expression changes were measured in the prostatectomy specimens. In PCa patients ingesting isoflavones, we observed significant decreases in prostate COX-2 mRNA and increases in p21 mRNA. There were significant correlations between COX-2 mRNA suppression, p21 mRNA stimulation and serum isoflavone levels. We propose that the inhibition of the PG pathway contributes to the beneficial effect of soy isoflavones in PCa chemoprevention and/or treatment. PMID:19127598

  18. Severe and Moderate Asthma Exacerbations in Asthmatic Children and Exposure to Ambient Air Pollutants

    PubMed Central

    Tétreault, Louis-Francois; Doucet, Marieve; Gamache, Philippe; Fournier, Michel; Brand, Allan; Kosatsky, Tom; Smargiassi, Audrey

    2016-01-01

    Background: It is well established that short-term exposure to ambient air pollutants can exacerbate asthma, the role of early life or long-term exposure is less clear. We assessed the association between severe asthma exacerbations with both birth and annual exposure to outdoor air pollutants with a population-based cohort of asthmatic children in the province of Quebec (Canada). Method: Exacerbations of asthma occurring between 1 April 1996 and 31 March 2011 were defined as one hospitalization or emergency room visit with a diagnosis of asthma for children (<13 years old) already diagnosed with asthma. Annual daily average concentrations of ozone (O3) and nitrogen dioxide (NO2) were estimated at the child’s residential postal code. Satellite based levels of fine particulate (PM2.5) estimated for a grid of 10 km by 10 km were also assigned to postal codes of residence for the whole province. Hazard ratios (HRs) were estimated from Cox models with a gap time approach for both birth and time-dependant exposure. Results: Of the 162,752 asthmatic children followed (1,020,280 person-years), 35,229 had at least one asthma exacerbation. The HRs stratified by age groups and adjusted for the year of birth, the ordinal number of exacerbations, sex, as well as material and social deprivation, showed an interquartile range increase in the time-dependant exposure to NO2 (4.95 ppb), O3 (3.85 ppb), and PM2.5 (1.82 μg/m3) of 1.095 (95% CI 1.058–1.131), 1.052 (95% CI 1.037–1.066) and 1.025 (95% CI 1.017–1.031), respectively. While a positive association was found to PM2.5, no associations were found between exposure at birth to NO2 or O3. Conclusions: Our results support the conclusion, within the limitation of this study, that asthma exacerbations in asthmatic children are mainly associated with time dependent residential exposures less with exposure at birth. PMID:27490556

  19. Cannabinoids inhibit cholinergic contraction in human airways through prejunctional CB1 receptors

    PubMed Central

    Grassin-Delyle, S; Naline, E; Buenestado, A; Faisy, C; Alvarez, J-C; Salvator, H; Abrial, C; Advenier, C; Zemoura, L; Devillier, P

    2014-01-01

    Background and Purpose Marijuana smoking is widespread in many countries, and the use of smoked synthetic cannabinoids is increasing. Smoking a marijuana joint leads to bronchodilation in both healthy subjects and asthmatics. The effects of Δ9-tetrahydrocannabinol and synthetic cannabinoids on human bronchus reactivity have not previously been investigated. Here, we sought to assess the effects of natural and synthetic cannabinoids on cholinergic bronchial contraction. Experimental Approach Human bronchi isolated from 88 patients were suspended in an organ bath and contracted by electrical field stimulation (EFS) in the presence of the phytocannabinoid Δ9-tetrahydrocannabinol, the endogenous 2-arachidonoylglycerol, the synthetic dual CB1 and CB2 receptor agonists WIN55,212-2 and CP55,940, the synthetic, CB2-receptor-selective agonist JWH-133 or the selective GPR55 agonist O-1602. The receptors involved in the response were characterized by using selective CB1 and CB2 receptor antagonists (SR141716 and SR144528 respectively). Key Results Δ9-tetrahydrocannabinol, WIN55,212-2 and CP55,940 induced concentration-dependent inhibition of cholinergic contractions, with maximum inhibitions of 39, 76 and 77% respectively. JWH-133 only had an effect at high concentrations. 2-Arachidonoylglycerol and O-1602 were devoid of any effect. Only CB1 receptors were involved in the response because the effects of cannabinoids were antagonized by SR141716, but not by SR144528. The cannabinoids did not alter basal tone or contractions induced by exogenous Ach. Conclusions and Implications Activation of prejunctional CB1 receptors mediates the inhibition of EFS-evoked cholinergic contraction in human bronchus. This mechanism may explain the acute bronchodilation produced by marijuana smoking. PMID:24467410

  20. Influence of vascular endothelial growth factor inhibition on simple renal cysts in patients receiving bevacizumab-based chemotherapy

    PubMed Central

    Shavit, Linda

    2015-01-01

    Purpose Although angiogenesis has been implicated in the promotion of renal cyst growth in autosomal dominant polycystic kidney disease, no studies have investigated the role of angiogenesis in the growth of simple renal cysts. The aim of current study was to investigate the effect of chemotherapy with the antivascular endothelial growth factor antibody bevacizumab on renal cyst development and growth in cancer patients. Materials and Methods We retrospectively reviewed the medical records of 136 patients with a variety of cancers that were treated with bevacizumab-based chemotherapy for metastatic disease. The presence of and changes in renal cysts were evaluated by retrospective analysis of computed tomography scans performed for assessment of tumor response to bevacizumab-based therapy. Results The median age of the patients was 64 years. Renal cysts were identified in 66 patients, in whom 33 (50%) had a single cyst and the rest had 2 or more cysts. The average dose of bevacizumab was 2.68 mg/kg per week. Median duration of treatment was 33 weeks. Average cyst size was 1.9±2.4 cm at the beginning of the study and the majority of the cysts (54 patients, 84%) did not change in size or shape during bevacizumab treatment. No patients were identified with new cysts. Cyst size changed in 10 patients (16%): an increase of 15% to 40% from the baseline size in 5 patients and a decrease in size of 10% to 70% in another 5 patients. The duration of bevacizumab therapy was significantly longer in the subgroup of patients with diminished or increased cyst size than in the patients with stable cyst size: 62 weeks versus 29 weeks, respectively (p=0.0002). Conclusions Our data demonstrated that simple renal cysts were stable in size and number in the vast majority of cancer patients treated with bevacizumab. PMID:26682018

  1. A study of granulocyte respiratory burst in patients with allergic bronchial asthma.

    PubMed

    Vargas, L; Patiño, P J; Montoya, F; Vanegas, A C; Echavarría, A; García de Olarte, D

    1998-02-01

    The respiratory burst of phagocytes plays an important role in the tissue damage that accompanies the inflammatory response. One of these conditions is allergic bronchial asthma, therefore, to evaluate the activation state of peripheral granulocytes the generation of reactive oxygen metabolites was evaluated using Luminol-enhanced chemiluminescence (LCL) and reduction of cytochrome C by superoxide. The resting granulocytes of the asthmatic patients under crisis showed a higher LCL compared to the noncrisis patients and control subjects. The granulocytes stimulated with PMA presented a significant increase in the respiratory burst in both groups of asthmatics. The granulocytes of noncrisis asthmatics challenged with Ops-Zym and with fMLP + Ops-Zym showed a higher metabolic activity, whereas the asthmatics under crisis presented no difference between reactive oxygen generation and that of the control group. The quantitative analysis of superoxide generation by granulocytes of the same patients did not show differences among the groups. Our findings suggest that the granulocytes of crisis and noncrisis asthmatics seem to be in a hyperreactive state and with a higher metabolic response when compared to the control group. However, the patients present a different behavior depending on stimulus used to activate cells. This could indicate that in peripheral blood exist different granulocyte populations depending on the inflammatory response taking place in the respiratory tract. PMID:9484649

  2. Inhibition of P-glycoprotein in Caco-2 cells: effects of herbal remedies frequently used by cancer patients.

    PubMed

    Engdal, S; Nilsen, O G

    2008-06-01

    1. The herbal products Natto K2, Agaricus, mistletoe, noni juice, green tea and garlic were investigated for in vitro inhibitory potential on P-glycoprotein (P-gp)-mediated transport of digoxin (30 nM) in differentiated and polarized Caco-2 cells. 2. Satisfactory cell functionality was demonstrated through measurements of assay linearity, transepithelial electric resistance (TEER), cytotoxicity, mannitol permeability, and inclusion of the positive inhibition control verapamil. 3. The most potent inhibitors of the net digoxin flux (IC(50)) were mistletoe > Natto K2 > Agaricus > green tea (0.022, 0.62, 3.81, >4.5 mg ml(-1), respectively). Mistletoe also showed the lowest IC(25) value, close to that obtained by verapamil (1.0 and 0.5 microg ml(-1), respectively). The IC(50)/IC(25) ratio was found to be a good parameter for the determination of inhibition profiles. Garlic and noni juice were classified as non-inhibitors. 4. This study shows that mistletoe, Natto K2, Agaricus and green tea inhibit P-gp in vitro. Special attention should be paid to mistletoe due to very low IC(50) and IC(25) values and to Natto K2 due to a low IC(50) value and a low IC(50)/IC(25) ratio. PMID:18570158

  3. Inhibition of Gastric Acid Secretion by H2 Receptor Antagonists Associates a Definite Risk of Enteric Peritonitis and Infectious Mortality in Patients Treated with Peritoneal Dialysis

    PubMed Central

    Pérez-Fontan, Miguel; Machado Lopes, Daniela; García Enríquez, Alba; López-Calviño, Beatriz; López-Muñiz, Andrés; García Falcón, Teresa; Rodríguez-Carmona, Ana

    2016-01-01

    Background Evidences linking treatment with inhibitors of gastric acid secretion (IGAS) and an increased risk of serious infections are inconclusive, both in the population at large and in the particular case of patients with chronic kidney disease. We have undertaken an investigation to disclose associations between treatment with IGAS and infectious outcomes, in patients undergoing chronic Peritoneal Dialysis (PD). Method Observational, historic cohort, single center design. Six hundred and ninety-one patients incident on PD were scrutinized for an association among treatment with IGAS (H2 antagonists H2A or proton pump inhibitors PPI) (main study variable), on one side, and the risks of enteric peritoneal infection (main outcome), overall peritoneal infection, and general and infectious mortality (secondary outcomes). We applied a three-step multivariate approach, based on classic Cox models (baseline variables), time-dependent analyses and, when appropriate, competing risk analyses. Main results The clinical characteristics of patients treated with H2A, PPI or none of these were significantly different. Multivariate analyses disclosed a consistently increased risk of enteric peritonitis in patients treated with IGAS (RR 1.65, 95% CI 1.08–2.55, p = 0.018, Cox). Stratified analysis indicated that patients treated with H2A, rather than those on PPI, supported the burden of this risk. Similar findings applied for the risk of infectious mortality. On the contrary, we were not able to detect any association among the study variables, on one side, and the general risks of peritonitis or mortality, on the other. Conclusions Treatment with IGAS associates increased incidences of enteric peritonitis and infectious mortality, among patients on chronic PD. The association is clear in the case of H2A but less consistent in the case of PPI. Our results support the convenience of preferring PPI to H2A, for gastric acid inhibition in PD patients. PMID:26872254

  4. The cyclopentenone 15-deoxy-delta(12,14)-prostaglandin J2 inhibits G1/S transition and retinoblastoma protein phosphorylation in immortalized lymphocytes from Alzheimer's disease patients.

    PubMed

    Muñoz, Ursula; de Las Cuevas, Natividad; Bartolomé, Fernando; Hermida, Ofelia G; Bermejo, Félix; Martín-Requero, Angeles

    2005-10-01

    Epidemiologic studies indicated that non-steroidal anti-inflammatory drugs (NSAIDs) might prevent or delay the clinical features of Alzheimer disease (AD). The pharmacological activity of NSAIDs is generally attributed to inhibition of cyclooxygenase and peroxisome proliferator-activated receptor gamma (PPARgamma) activation. Based on the antineoplastic and apoptotic effects of PPARgamma activation in a number of cell types, we hypothesized that NSAIDs could protect neurons by controlling the regulation of cell cycle. Recent work suggests that uncoordinated expression of cell cycle molecules and perturbation of cell cycle checkpoints may be one of the mechanisms by which post-mitotic neurons die. Since cell cycle dysfunction is not restricted to neurons in AD, we found it interesting to study the role of PPARgamma activation on cell proliferation in immortalized lymphocytes from AD patients. We report here that 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2), but not NSAIDs or thiazolidinediones inhibited the serum-mediated enhancement of cell proliferation in AD by blocking the events critical for G1/S transition. The cyclopentenone induced a partial inhibition of retinoblastoma protein phosphorylation and increased levels of the CDK inhibitor p27kip1. PMID:16061222

  5. Domestic exposure to fungi and total serum IgE levels in asthmatic children.

    PubMed

    Su, Huey-Jen Jenny; Wu, Pei-Chih; Lei, Huan-Yao; Wang, Jiu-Yao

    2005-08-14

    We measured the number of airborne, viable fungi and house dust mite (HDM) allergen levels in the homes of a group of asthmatic children. Blood samples were drawn and the amounts of total and specific serum IgE were determined. The association between the number of fungal colonies, dust mite allergen exposure, and specific and total IgE was evaluated. The number of viable airborne fungi was high (20,543 CFU/m(3)) in those investigated houses. Der p1 concentrations on child's mattress exceeding 2 microg/g were found in 78.6% of the houses. A quantitative dose-response relationship was demonstrated between the exposure to viable, airborne molds and the amount of total IgE (r = 0.4399 and P = .0249) and the level was further increased in children with coexposure to viable fungi and HDM. PMID:16106103

  6. A systematic review of lung function testing in asthmatic young children.

    PubMed

    Ioan, Iulia; Varechova, Silvia; Marchal, François; Pleşca, Doina-Anca

    2015-01-01

    Asthma diagnosis is difficult in young children being mainly based on clinical signs and parents' history, which is sometimes difficult to obtain. Lung function testing may improve asthma diagnosis by objectively assessing its main features, airway obstruction, spontaneously reversible or after use of a bronchodilator drug, ventilation inhomogeneity during an acute bronchoconstriction and airway hyperresponsiveness. In young children that cannot cope with classical tests, it is important to use and develop simple, short lasting methods, made in spontaneous ventilation without active cooperation. Such techniques are a measurement of respiratory resistance by forced oscillations or the interrupter technique, of specific airway resistance by plethysmography and capnography. All these parameters are sensitive to the presence of an airway obstruction and to a bronchodilator or bronchoconstrictor agent, but their cutoff values in differentiating between asthmatic and healthy children as well as their specific indications in asthma management remain to be established. PMID:26506667

  7. Reduction in exhaled nitric oxide immediately after methacholine challenge in asthmatic children

    PubMed Central

    Piacentini, G; Bodini, A; Peroni, D; Del Giudice, M M.; Costella, S; Boner, A

    2002-01-01

    Background: The measurement of exhaled nitric oxide (NO) has recently been proposed as a useful technique for the evaluation of airway inflammation in asthma. The purpose of this study was to determine the effect of methacholine bronchial provocation on the levels of exhaled NO in asthmatic children. Method: Exhaled NO was measurement immediately before and after methacholine provocation in 51 children with mild to moderate asthma. Results: A significant decrease occurred in the level of exhaled NO (p<0.0001) after methacholine bronchial provocation which was not correlated with the percentage fall in forced expiratory volume in 1 second (FEV1). Conclusions: The methacholine test should not be used immediately before measurement of exhaled NO in children with asthma. PMID:12200520

  8. Assessment of a new device for delivering aerosol drugs to asthmatic children.

    PubMed Central

    Hodges, I G; Milner, A D; Stokes, G M

    1981-01-01

    A new device, known as the aero-chamber, for delivering aerosol drugs was compared with a standard aerosol inhaler in asthmatic children aged between 5 years 3 months and 13 years 10 months. The study was conducted under double-blind conditions using fenoterol, a beta 2 stimulant, as the active agent and a placebo. Response to treatment was assessed by measuring the peak expiratory flow rate before and after each inhaler. Seven of 10 children had greater mean improvements in peak expiratory flow rates when receiving the active drug from the aerochamber. The aerochamber offers a method for administering a whole range of canistered packaged drugs to children unable to use the standard inhalers. PMID:7030221

  9. Effects of Ambient Pollen Concentrations on Frequency and Severity of Asthma Symptoms Among Asthmatic Children

    PubMed Central

    Triche, Elizabeth W.; Leaderer, Brian P.; Bell, Michelle L.

    2011-01-01

    Background Previous studies on the associations between ambient pollen exposures and daily respiratory symptoms have produced inconsistent results. We investigated these relationships in a cohort of asthmatic children, using pollen exposure models to estimate individual ambient exposures. Methods Daily symptoms of wheeze, night symptoms, shortness of breath, chest tightness, persistent cough and rescue medication use were recorded in a cohort of 430 children age 4-12 years with asthma in Connecticut, Massachusetts and New York. Daily ambient exposures to tree, grass, weed and all-type pollen were estimated using mixed effects models. We stratified analyses by asthma maintenance medication and sensitization to grass or weed pollens. Separate logistic regression analysis using generalized estimating equations were performed for each symptom outcome and pollen type. We adjusted analyses for maximum daily temperature, maximum 8-hr average ozone, fine particles (PM2.5), season and antibiotic use. Results Associations were observed among children sensitized to specific pollens; these associations varied by use of asthma maintenance medication. Exposures to even relatively low levels of weed pollen (6-9 grains/m3) were associated with increased shortness of breath, chest tightness, rescue medication use, wheeze, and persistent cough, compared with lower exposure among sensitized children taking maintenance medication. Grass pollen exposures ≥2 grains/m3 were associated with wheeze, night symptoms, shortness of breath and persistent cough compared with lower exposure among sensitized children who did not take maintenance medication. Conclusion Even low-level pollen exposure was associated with daily asthmatic symptoms. PMID:22082997

  10. Allergic Non-Asthmatic Adults Have Regional Pulmonary Responses to Segmental Allergen Challenge

    PubMed Central

    Kelly, Vanessa J.; Winkler, Tilo; Venegas, Jose G.; Kone, Mamary; Hamilos, Daniel L.; Afshar, Roshi; Cho, Josalyn L.; Luster, Andrew D.; Medoff, Benjamin D.; Harris, R. Scott

    2015-01-01

    Background Allergic non-asthmatic (ANA) adults experience upper airway symptoms of allergic disease such as rhinorrhea, congestion and sneezing without symptoms of asthma. The aim of this study was to utilize PET-CT functional imaging to determine whether allergen challenge elicits a pulmonary response in ANA subjects or whether their allergic disease is truly isolated to the upper airways. Methods In 6 ANA subjects, bronchoalveolar lavages (BAL) were performed at baseline and 24h after instillation of an allergen and a diluent in separate lung lobes. After instillation (10h), functional imaging was performed to quantify and compare regional perfusion, ventilation, fractional gas content (Fgas), and glucose uptake rate (Ki) between the baseline, diluent and allergen lobes. BAL cell counts were also compared. Results In ANA subjects, compared to the baseline and diluent lobes, perfusion and ventilation were significantly lower in the allergen lobe (median [inter-quartile range], baseline vs. diluent vs. allergen: Mean-normalized perfusion; 0.87 [0.85–0.97] vs. 0.90 [0.86–0.98] vs. 0.59 [0.55–0.67]; p<0.05. Mean-normalized ventilation 0.89 [0.88–0.98] vs. 0.95 [0.89–1.02] vs. 0.63 [0.52–0.67], p<0.05). In contrast, no significant differences were found in Fgas between baseline, diluent and allergen lobes or in Ki. Total cell counts, eosinophil and neutrophil cell counts (cells/ml BAL) were significantly greater in the allergen lobe compared to the baseline lobe (all P<0.05). Conclusions Despite having no clinical symptoms of a lower airway allergic response (cough and wheeze) allergic non-asthmatic subjects have a pulmonary response to allergen exposure which manifests as reduced ventilation and perfusion. PMID:26640951

  11. Bronchial hyperresponsiveness to mannitol, airway inflammation and Asthma Control Test in atopic asthmatic children

    PubMed Central

    Consilvio, Nicola P.; Rapino, Daniele; Nicola, Marta Di; Scaparrotta, Alessandra; Cingolani, Anna; Petrosino, Marianna I.; Filippo, Paola Di; Pillo, Sabrina Di; Chiarelli, Francesco

    2016-01-01

    Introduction The aim of this study was to evaluate the relationship between airway hyperresponsiveness (AHR) to mannitol and bronchial inflammation measured as exhaled nitric oxide (FeNO) and to assess whether asthma control correlates with AHR to mannitol and FeNO in atopic asthmatic children. Material and methods Allergy evaluation, the mannitol challenge test, FeNO levels and the Asthma Control Test (ACT) questionnaire were assessed in 40 children with intermittent and mild persistent allergic asthma. Results All the subjects showed positive AHR to mannitol. Pearson's correlation test revealed a significant inverse correlation between AHR (mannitol PD15) and FeNO (p = 0.020). There was also a significant positive correlation between ACT and PD15 (p = 0.020) and a significant negative correlation between ACT and FeNO levels (p = 0.003). The study population was divided into two groups according to FeNO levels (group A ≥ 16 ppb vs. group B < 16 ppb). In group A mannitol PD15 was significantly lower (p = 0.040) and ACT score values were significantly lower (p = 0.001) compared to group B. In group A, the ACT showed that 13.3% of subjects had well-controlled asthma, 80% had partially controlled asthma and 6.7% had uncontrolled asthma. In group B, the ACT showed that 72% of subjects had well-controlled asthma and 28% had partially controlled asthma. Conclusions Our findings indicate that the degree of AHR to mannitol correlates with the degree of airway inflammation in asthmatic atopic children; moreover, better control of asthma correlates with a lower degree of AHR to both mannitol and FeNO. PMID:26925129

  12. House-plant placement for indoor air purification and health benefits on asthmatics

    PubMed Central

    Kim, Ho-Hyun; Yang, Ji-Yeon; Lee, Jae-Young; Park, Jung-Won; Kim, Kwang-Jin; Lim, Byung-Seo; Lee, Geon-Woo; Lee, Si-Eun; Shin, Dong-Chun; Lim, Young-Wook

    2014-01-01

    Objectives Some plants were placed in indoor locations frequented by asthmatics in order to evaluate the quality of indoor air and examine the health benefits to asthmatics. Methods The present study classified the participants into two groups: households of continuation and households of withdrawal by a quasi-experimental design. The households of continuation spent the two observation terms with indoor plants, whereas the households of withdrawal passed the former observation terms with indoor plants and went through the latter observation term without any indoor plants. Results The household of continuation showed a continual decrease in the indoor concentrations of volatile organic compounds (VOCs) during the entire observation period, but the household of withdrawal performed an increase in the indoor concentrations of VOCs, except formaldehyde and toluene during the latter observation term after the decrease during the former observation term. Peak expiratory flow rate (PEFR) increased in the households of continuation with the value of 13.9 L/min in the morning and 20.6 L/ min in the evening, but decreased in the households of withdrawal with the value of -24.7 L/min in the morning and -30.2 L/min in the evening in the first experimental season. All of the households exhibited a decrease in the value of PEFR in the second experimental season. Conclusions Limitations to the generalizability of findings regarding the presence of plants indoors can be seen as a more general expression of such a benefit of human-environment relations. PMID:25384387

  13. Pharmacological Inactivation of Src Family Kinases Inhibits LPS-Induced TNF-α Production in PBMC of Patients with Behçet's Disease

    PubMed Central

    Pektanc, Gulsum; Akkurt, Zeynep M.; Bozkurt, Mehtap; Turkcu, Fatih M.; Kalkanli-Tas, Sevgi

    2016-01-01

    Behçet's disease (BD) is a multisystemic chronic inflammatory disease characterized by relapsing oral and genital ulcers, uveitis, and skin lesions. The pathogenesis of BD is still unknown. Aberrant production of some cytokines/chemokines plays an important role in the pathogenesis of various inflammatory diseases. Revealing a key signaling regulatory mechanism involved in proinflammatory cytokines/chemokines production is critical for understanding of the pathogenesis of BD. The aim of this study was to determine the role of Src family kinases (SFKs) in production of some LPS-induced proinflammatory cytokines/chemokines in peripheral blood mononuclear cells (PBMC) of active BD patients. Chemical inhibition of SFKs activity impaired LPS-induced TNF-α production in PBMC of active BD patients, suggesting that modulating SFKs activity may be a potential target for BD treatment. PMID:27445436

  14. CIRCULATING NEUTROPHIL CD14 EXPRESSION REVERSE THE INVERSE ASSOCIATION OF AMBIENT PM2.5 AND PM10-2.5 ON LUNG FUNCTION IN ASTHMATIC CHILDREN

    EPA Science Inventory

    Background: Identifying biomarkers that predict susceptibility to size-specific PM independent of gaseous pollutants could help us better identify asthmatic subpopulations at increased risk to the adverse health effects of PM. Objective: Our objective was to assess the associatio...

  15. Facilitating and inhibiting factors for long-term involvement of patients at outcome conferences—lessons learnt from a decade of collaboration in OMERACT: a qualitative study

    PubMed Central

    de Wit, Maarten; Abma, Tineke; Koelewijn-Van Loon, Marije; Collins, Sarah; Kirwan, John

    2013-01-01

    Objective Several studies have provided insights into the conditions for successful patient involvement in health research. We recently demonstrated that long-term engagement with people with rheumatic conditions in international outcome research led to significant changes in the research agenda in the field of rheumatology. This article explores facilitating and inhibiting factors for long-term involvement of patients as collaborative partners at five Outcome Measures in Rheumatology (OMERACT) conferences. Design Responsive evaluation, starting with a thematic document analysis of conference proceedings and the grey literature, followed by 38 qualitative interviews. Interview transcripts were subjected to inductive content analysis. Setting 5 international OMERACT conferences between 2002 and 2012. Participants Patient delegates (n=16) and professional delegates representing researchers (n=14), pharmaceutical industry and regulators (n=2). Results Combined review of the document analysis and interview data revealed five main facilitators and three main barriers. Patient engagement as full participants at OMERACT conferences was enhanced by: strong leadership commitment and the presence of change agents, a clear selection procedure, an inclusive consensus-based conference design, individualised and self-organised support, an interactive and encouraging moderation style during discussion groups. Barriers were related to the intensity of the conference programme, scepticism among researchers and doubts about the representativeness of the patient group. Conclusions This study concludes that developing a sustainable structure for funding, selection and support of patient delegates, as well as adjusting conference design and moderation style, contributes not only towards facilitating direct dialogue between all stakeholders but also towards enhancing mutual understanding and the successful incorporation of the patient perspective in an outcome conference such as OMERACT

  16. Effects of Angiotensin Converting Enzyme Inhibition or Angiotensin Receptor Blockade in Dialysis Patients: A Nationwide Data Survey and Propensity Analysis

    PubMed Central

    Wu, Cho-Kai; Yang, Yao-Hsu; Juang, Jyh-Ming Jimmy; Wang, Yi-Chih; Tsai, Chia-Ti; Lai, Ling-Ping; Hwang, Juey-Jen; Chiang, Fu-Tien; Chen, Pau-Chung; Lin, Jiunn-Lee; Lin, Lian-Yu

    2015-01-01

    Abstract Long-term benefit of using a renin–angiotensin–aldosterone system blocker such as an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) for patients already receiving dialysis remains undetermined. The aim of this study is to assess the efficacy and safety of ACEI or ARB use in dialysis patients. We performed a population-based cohort study with time-to-event analyses to estimate the relation between the use of ACEI/ARB and their outcomes. We used a nationwide database (Registry for Catastrophic Illnesses) for Taiwan, which has data from 1995 to 2008 nearly of all patients who received dialysis therapy. The records of all dialysis patients aged ≥18 with no evidence of cardiovascular (CV) events in 1997 and 1998 (133,564 patients) were examined. Users (n = 50,961) and nonusers (n = 59,913) of an ACEI/ARB were derived. We then used propensity score matching and Cox proportional hazards regression models to estimate adjusted hazard ratios (HRs) for all-cause mortality and CV events in users and nonusers of an ACRI/ARB. The 15,182 patients, who used an ACEI/ARB, and the 15,182 nonusers had comparable baseline characteristics during the 14 years of follow-up. The mortality was significantly greater in patients who did not use an ACEI/ARB (HR = 0.90, 95% confidence interval = 0.86–0.93). Subgroup analysis of 3 tertiles of patients who used different total amounts of ACEI/ARB during the study period indicated that CV events were more common in patients who used an ACEI/ARB for a short duration (tertile 1: HR = 1.63), but less common in those who used an ACEI/ARB for long durations (tertile 2: HR = 1.05; tertile 3: HR = 0.94; trend for declining HR from tertile 1 to 3: P < 0.001). The mortality benefit provided by use of an ACEI/ARB was consistent across most patient subgroups, as was the benefit of ARB monotherapy rather than ACEI monotherapy. Independent of traditional risk factors

  17. Leukotriene E(4) in urine in patients with asthma and COPD--the effect of smoking habit.

    PubMed

    Gaki, E; Papatheodorou, G; Ischaki, E; Grammenou, V; Papa, I; Loukides, S

    2007-04-01

    Leukotriene E(4) (LTE(4)) is implicated in asthma pathophysiology and possibly in chronic obstructive pulmonary disease (COPD) as one of the causes of persistent bronchoconstriction and mucus hypersecretion. Cigarette smoking stimulates cysteinyl leukotrienes (CysLTs) production. We investigated whether LTE(4) is equally increased in asthma and COPD and whether smoking significantly affects LTE(4) levels. Secondary outcomes involved correlations with inflammatory and functional parameters. We studied 40 patients with COPD [20 smokers], 40 asthmatics [20 smokers] and 30 healthy subjects [15 smokers]. Spirometry (FEV(1)% pred., FEV(1)/FVC) was performed, urine was collected for measurement of LTE(4) and creatinine, induced sputum was collected for differential cell counts and serum for ECP. LTE(4)/creatinine levels (pg/mg) [mean (sd)] were increased in asthmatic patients compared to COPD and controls, [125.6(54.5) vs. 54.5(19) vs. 55.9(18.9)pg/mg, respectively, P<0.0001 for asthma]. Smoking significantly affects LTE(4) levels only in asthmatic patients [164 (48) vs. 87 (26.3), P<0.0001 for smokers]. The only significant correlation was between eosinophils in induced sputum and LTE(4)/creatinine levels in asthmatics. In conclusion, patients with asthma presented higher LTE(4) values compared to normals and patients with COPD. Smoking significantly affects LTE(4) values only in asthmatics indicating a different underlying CysLTs inflammatory process in this condition. PMID:16965907

  18. Early inhibition of natural and interferon-activated killers in endometrial cancer patients treated with local radiotherapy

    SciTech Connect

    Mandeville, R.; Sidrac-Ghali, S.; Ajdukovic, I.; Vidal, D.; Ayoub, J.

    1987-01-01

    The present study was aimed at comparing the effect of clinical staging and radiotherapy on natural killer (NK) and interferon-activated killer (IAK) cell activity in a group of endometrial cancer patients receiving a total dose of 5,000 to 8,000 rads. We report that when compared to age-matched women, a significantly higher number and percentage of patients show low NK and IAK cell activity. At diagnosis, diminished NK activity was seen in about 20% of the patients, while IAK activity was low in 49% of these patients. There was no correlation between these deficiencies and the grade or stage of the disease. In contrast, radiotherapy induced deleterious effects on both populations of NK and IAK cells. These deleterious effects were more pronounced in patients showing a low level of spontaneous NK activity. In an attempt to understand better the mechanism by which the presence of cancer itself and/or radiotherapy affects these activities, we studied in greater detail changes in peripheral blood T-cell numbers and subsets. Before radiotherapy, all lymphocyte counts were within the normal range. In contrast, after radiotherapy the absolute numbers of all T-cell subsets were significantly decreased in the majority of the patients tested, OKT4+ cells being the most radiosensitive and Leu 7+ cells the most radioresistant.

  19. Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy

    PubMed Central

    2015-01-01

    We hypothesised that tumour necrosis factor-α (TNF-α) may enhance receptor activator of nuclear factor-κβ ligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and cultured in vitro on plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF-α (anti-TNF-α). Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p > 0.05), there was a significant increase in the area of resorption on the surface (p < 0.01) and under the surface (p < 0.01) in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF-α resulted in a significant reduction in the area of resorption on the surface (p < 0.05) and under the surface (p < 0.05) only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF-α modulates RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy. PMID:26137498

  20. Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy.

    PubMed

    Petrova, Nina L; Petrov, Peter K; Edmonds, Michael E; Shanahan, Catherine M

    2015-01-01

    We hypothesised that tumour necrosis factor-α (TNF-α) may enhance receptor activator of nuclear factor-κβ ligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and cultured in vitro on plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF-α (anti-TNF-α). Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p > 0.05), there was a significant increase in the area of resorption on the surface (p < 0.01) and under the surface (p < 0.01) in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF-α resulted in a significant reduction in the area of resorption on the surface (p < 0.05) and under the surface (p < 0.05) only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF-α modulates RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy. PMID:26137498

  1. [Dexamethasone increases the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in lung tissues of bronchial asthmatic mice].

    PubMed

    Li, Zhenxing; He, Sheng; Wei, Liping; Lin, Lin; Xiong, Hanzhen; Li, Junhong; Chen, Peifen; Lai, Wenyan

    2016-05-01

    Objective To investigate the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in the lung tissues of bronchial asthmatic mice and the effect of dexamethasone treatment on its expression. Methods Thirty BALB/c mice were randomly divided into three equal groups: a control group, an asthmatic group and a dexamethasone-treated group. The asthmatic mouse models were established by intraperitoneal injection and inhalation with ovalbumin (OVA). The number of eosinophils (EOS) and lymphocytes (Lym) in bronchoalveolar lavage fluid (BALF) were counted. HE staining was used to observe airway inflammation and remodeling. The mRNA and protein expression of RECK were determined by real-time PCR and immunohistochemistry, respectively. Results Compared with the control group and the dexamethasone-treated group, the total cell number and EOS number in the BALF of the asthma group significantly increased. The expression of RECK mRNA in the asthmatic group was significantly lower than that in the control group and the dexamethasone-treated group. Immunohistochemistry showed that RECK was mainly expressed in the airway epithelial cells and inflammatory cells. RECK protein expression was highest in the control group and lowest in the asthmatic group. Conclusion Dexamethasone can increase the expression of RECK in the lung tissues of asthmatic mice. PMID:27126937

  2. Relationship between lung function and quantitative computed tomographic parameters of airway remodeling, air trapping, and emphysema in patients with asthma and chronic obstructive pulmonary disease: A single-center study

    PubMed Central

    Hartley, Ruth A.; Barker, Bethan L.; Newby, Chris; Pakkal, Mini; Baldi, Simonetta; Kajekar, Radhika; Kay, Richard; Laurencin, Marie; Marshall, Richard P.; Sousa, Ana R.; Parmar, Harsukh; Siddiqui, Salman; Gupta, Sumit; Brightling, Chris E.

    2016-01-01

    Background There is a paucity of studies comparing asthma and chronic obstructive pulmonary disease (COPD) based on thoracic quantitative computed tomographic (QCT) parameters. Objectives We sought to compare QCT parameters of airway remodeling, air trapping, and emphysema between asthmatic patients and patients with COPD and explore their relationship with airflow limitation. Methods Asthmatic patients (n = 171), patients with COPD (n = 81), and healthy subjects (n = 49) recruited from a single center underwent QCT and clinical characterization. Results Proximal airway percentage wall area (%WA) was significantly increased in asthmatic patients (62.5% [SD, 2.2]) and patients with COPD (62.7% [SD, 2.3]) compared with that in healthy control subjects (60.3% [SD, 2.2], P < .001). Air trapping measured based on mean lung density expiratory/inspiratory ratio was significantly increased in patients with COPD (mean, 0.922 [SD, 0.037]) and asthmatic patients (mean, 0.852 [SD, 0.061]) compared with that in healthy subjects (mean, 0.816 [SD, 0.066], P < .001). Emphysema assessed based on lung density measured by using Hounsfield units below which 15% of the voxels lie (Perc15) was a feature of COPD only (patients with COPD: mean, −964 [SD, 19.62] vs asthmatic patients: mean, −937 [SD, 22.7] and healthy subjects: mean, −937 [SD, 17.1], P < .001). Multiple regression analyses showed that the strongest predictor of lung function impairment in asthmatic patients was %WA, whereas in the COPD and asthma subgrouped with postbronchodilator FEV1 percent predicted value of less than 80%, it was air trapping. Factor analysis of QCT parameters in asthmatic patients and patients with COPD combined determined 3 components, with %WA, air trapping, and Perc15 values being the highest loading factors. Cluster analysis identified 3 clusters with mild, moderate, or severe lung function impairment with corresponding decreased lung density (Perc15 values) and increased air

  3. To RAS or not to RAS? The evidence for and cautions with renin-angiotensin system inhibition in patients with diabetic kidney disease.

    PubMed

    St Peter, Wendy L; Odum, Lauren E; Whaley-Connell, Adam T

    2013-05-01

    Substantial morbidity, mortality, and costs are associated with progressive diabetic kidney disease (DKD). A goal of Healthy People 2020 is to reduce kidney disease attributable to diabetes mellitus and increase the proportion of patients who receive agents that interrupt the renin-angiotensin system (RAS), such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). The mechanisms that contribute to progressive loss of kidney function in patients with diabetes are disrupted by inhibition of the RAS. ACEIs, ARBs and direct renin inhibitors (DRIs) all reduce the effect of angiotensin II, yet each works through a different mechanism and displays properties that may or may not be replicated by the others. As single agents, RAS inhibitors and blockers have been shown to slow the rate of progression of DKD and to reduce new cases of end-stage renal disease in various subsets of patients with diabetes and proteinuria (e.g., albuminuria). However, even with contemporary use of ACEIs, ARBs, and, more recently, DRIs, the burden of kidney disease remains high. Thus investigators sought to explore the utility of combining agents (e.g., dual RAS therapy) in various regimens for cardiovascular and kidney end points. Recent data from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) studies suggest that kidney-related outcomes (composite of dialysis initiation, doubling serum creatinine concentration, or death) were increased with ACEI plus ARB or DRI plus ARB combinations. Consequently, dual therapy should not be routinely prescribed in patients with diabetes until further data become available from other future studies. This review provides an introduction to DKD and a rationale for using RAS inhibition; discusses screening, detection, and monitoring of patients with DKD; and summarizes results from meta-analyses and

  4. Combined BRAF (Dabrafenib) and MEK Inhibition (Trametinib) in Patients With BRAFV600-Mutant Melanoma Experiencing Progression With Single-Agent BRAF Inhibitor

    PubMed Central

    Johnson, Douglas B.; Flaherty, Keith T.; Weber, Jeffrey S.; Infante, Jeffrey R.; Kim, Kevin B.; Kefford, Richard F.; Hamid, Omid; Schuchter, Lynn; Cebon, Jonathan; Sharfman, William H.; McWilliams, Robert R.; Sznol, Mario; Lawrence, Donald P.; Gibney, Geoffrey T.; Burris, Howard A.; Falchook, Gerald S.; Algazi, Alain; Lewis, Karl; Long, Georgina V.; Patel, Kiran; Ibrahim, Nageatte; Sun, Peng; Little, Shonda; Cunningham, Elizabeth; Sosman, Jeffrey A.; Daud, Adil; Gonzalez, Rene

    2014-01-01

    Purpose Preclinical and early clinical studies have demonstrated that initial therapy with combined BRAF and MEK inhibition is more effective in BRAFV600-mutant melanoma than single-agent BRAF inhibitors. This study assessed the safety and efficacy of dabrafenib and trametinib in patients who had received prior BRAF inhibitor treatment. Patients and Methods In this open-label phase I/II study, we evaluated the pharmacology, safety, and efficacy of dabrafenib and trametinib. Here, we report patients treated with combination therapy after disease progression with BRAF inhibitor treatment administered before study enrollment (part B; n = 26) or after cross-over at progression with dabrafenib monotherapy (part C; n = 45). Results In parts B and C, confirmed objective response rates (ORR) were 15% (95% CI, 4% to 35%) and 13% (95% CI, 5% to 27%), respectively; an additional 50% and 44% experienced stable disease ≥ 8 weeks, respectively. In part C, median progression-free survival (PFS) was 3.6 months (95% CI, 2 to 4), and median overall survival was 11.8 months (95% CI, 8 to 25) from cross-over. Patients who previously received dabrafenib ≥ 6 months had superior outcomes with the combination compared with those treated < 6 months; median PFS was 3.9 (95% CI, 3 to 7) versus 1.8 months (95% CI, 2 to 4; hazard ratio, 0.49; P = .02), and ORR was 26% (95% CI, 10% to 48%) versus 0% (95% CI, 0% to 15%). Conclusion Dabrafenib plus trametinib has modest clinical efficacy in patients with BRAF inhibitor–resistant melanoma. This regimen may be a therapeutic strategy for patients who previously benefited from BRAF inhibitor monotherapy ≥ 6 months but demonstrates minimal efficacy after rapid progression with BRAF inhibitor therapy. PMID:25287827

  5. Effects of Phosphodiesterase Type 5 Inhibition on Systemic and Pulmonary Hemodynamics and Ventricular Function in Patients with Severe Symptomatic Aortic Stenosis

    PubMed Central

    Lindman, Brian R.; Zajarias, Alan; Madrazo, José A.; Shah, Jay; Gage, Brian F.; Novak, Eric; Johnson, Stephanie N.; Chakinala, Murali M.; Hohn, Tara A.; Saghir, Mohammed; Mann, Douglas L.

    2012-01-01

    Background Pressure overload due to aortic stenosis (AS) causes maladaptive ventricular and vascular remodeling that can lead to pulmonary hypertension, heart failure symptoms, and adverse outcomes. Retarding or reversing this maladaptive remodeling and its unfavorable hemodynamic consequences has potential to improve morbidity and mortality. Preclinical models of pressure overload have shown that phosphodiesterase type 5 (PDE5) inhibition is beneficial, however the use of PDE5 inhibitors in patients with AS is controversial because of concerns about vasodilation and hypotension. Methods and Results We evaluated the safety and hemodynamic response of 20 subjects with severe symptomatic AS (mean aortic valve area 0.7±0.2 cm2, ejection fraction 60±14%) who received a single oral dose of sildenafil (40mg or 80mg). Compared to baseline, after 60 minutes sildenafil reduced systemic (−12%, p<0.001) and pulmonary (−29%, p=0.002) vascular resistance, mean pulmonary artery (−25%, p<0.001) and wedge (−17%, p<0.001) pressure, and increased systemic (+13%, p<0.001) and pulmonary (+45%, p<0.001) vascular compliance and stroke volume index (+8%, p=0.01). These changes were not dose dependent. Sildenafil caused a modest decrease in mean systemic arterial pressure (−11%, p<0.001), but was well-tolerated with no episodes of symptomatic hypotension. Conclusions This study shows for the first time that a single dose of a PDE5 inhibitor is safe and well-tolerated in patients with severe AS and is associated with acute improvements in pulmonary and systemic hemodynamics resulting in biventricular unloading. These findings support the need for longer-term studies to evaluate the role of PDE5 inhibition as adjunctive medical therapy in patients with AS. PMID:22447809

  6. The E3 ubiquitin ligase Cbl-b improves the prognosis of RANK positive breast cancer patients by inhibiting RANKL-induced cell migration and metastasis.

    PubMed

    Zhang, Lingyun; Teng, Yuee; Fan, Yibo; Wang, Yan; Li, Wei; Shi, Jing; Ma, Yanju; Li, Ce; Shi, Xiaonan; Qu, Xiujuan; Liu, Yunpeng

    2015-09-01

    The receptor activator of nuclear factor κ-B ligand (RANKL)/RANK pathway plays an important role in breast cancer progression. Despite the known role of Casitas B-lineage lymphoma (Cbl)-b as an essential regulator of the RANKL/RANK pathway, its effect on RANK pathway in breast cancer remains unclear. Thus, the present study investigated the effect of Cbl-b on the prognosis of RANK-expressing breast cancer patients, as well as on RANKL/RANK pathway. The results showed that RANK and Cbl-b expression was separately detected in 154 (154/300, 51.3%) and 165 (165/300, 55.0%) breast cancer tissue samples. In RANK-expressing breast cancer patients, Cbl-b expression was correlated with low metastasis rate (p = 0.004), better disease-free survival (DFS) and breast cancer-specific survival (BCSS) (p = 0.004 and p = 0.036, respectively). In addition, multivariate analysis showed that Cbl-b expression was an independent predictor of DFS (p = 0.038). Animal experiment results demonstrated that silencing Cbl-b expression in breast cancer cells increased the incidence of lung metastasis in nude mice. Further mechanism investigation revealed that Cbl-b down-regulated RANK protein expression and inhibited RANKL-induced breast cancer cell migration by negatively regulating the Src-Akt/ERK pathway. Our results suggest that Cbl-b improves the prognosis of RANK-expressing breast cancer patients by inhibiting RANKL-induced breast cancer cell migration and metastasis. PMID:26087197

  7. In Silico Investigation of Traditional Chinese Medicine Compounds to Inhibit Human Histone Deacetylase 2 for Patients with Alzheimer's Disease

    PubMed Central

    Hung, Tzu-Chieh; Lee, Wen-Yuan; Chen, Kuen-Bao; Chan, Yueh-Chiu; Lee, Cheng-Chun

    2014-01-01

    Human histone deacetylase 2 (HDAC2) has been identified as being associated with Alzheimer's disease (AD), a neuropathic degenerative disease. In this study, we screen the world's largest Traditional Chinese Medicine (TCM) database for natural compounds that may be useful as lead compounds in the search for inhibitors of HDAC2 function. The technique of molecular docking was employed to select the ten top TCM candidates. We used three prediction models, multiple linear regression (MLR), support vector machine (SVM), and the Bayes network toolbox (BNT), to predict the bioactivity of the TCM candidates. Molecular dynamics simulation provides the protein-ligand interactions of compounds. The bioactivity predictions of pIC50 values suggest that the TCM candidatesm, (−)-Bontl ferulate, monomethylcurcumin, and ningposides C, have a greater effect on HDAC2 inhibition. The structure variation caused by the hydrogen bonds and hydrophobic interactions between protein-ligand interactions indicates that these compounds have an inhibitory effect on the protein. PMID:25045700

  8. Effects of the cyclooxygenase inhibiting nitric oxide donator naproxcinod versus naproxen on systemic blood pressure in patients with osteoarthritis.

    PubMed

    White, William B; Schnitzer, Thomas J; Fleming, Rosanna; Duquesroix, Brigitte; Beekman, Maarten

    2009-09-15

    Traditional nonsteroidal anti-inflammatory drugs are associated with the destabilization of blood pressure (BP) control, particularly in hypertensive patients treated with blockers of the renin-angiotensin system. To assess the potential impact of nitric oxide donation, the effects of naproxcinod with naproxen and placebo on changes in BP were compared in a randomized clinical trial of 916 patients with osteoarthritis after 13 weeks of therapy. In addition, the effects of naproxcinod versus naproxen and placebo on systolic BP in patients with hypertension treated with renin-angiotensin system blockers were evaluated. Naproxcinod 750 mg twice daily reduced systolic BP compared to naproxen 500 mg twice daily (p <0.02). The 2 doses of naproxcinod showed reductions from baseline in diastolic BP relative to naproxen (p <0.04) and similar changes compared to placebo. In 207 patients with hypertension treated with renin-angiotensin-blocking agents alone or with diuretics, the difference in mean change from baseline in systolic BP between naproxen 500 mg and naproxcinod 750 mg was 6.5 mm Hg in favor of naproxcinod (p <0.02). The proportion of patients in the overall population with systolic BP increases > or =10 mm Hg was greater with naproxen 500 mg (22%) compared to naproxcinod 750 mg (14%, p = 0.04), naproxcinod 375 mg (14%, p = 0.055), and placebo (15.6%, p = 0.155). In conclusion, naproxcinod did not induce elevations of BP seen with naproxen, and it had similar effects on BP to that of placebo in patients with osteoarthritis. PMID:19733721

  9. The effects of daily bathing on symptoms of patients with bronchial asthma

    PubMed Central

    Arimoto, Yoshihito; Homma, Chie; Takeoka, Shinjiro; Fukusumi, Munehisa; Mouri, Atsuto; Hamamoto, Yoichiro

    2016-01-01

    Background The influence of bathing in asthma patients is not yet fully known. Objective We conducted an observational study to investigate changes in symptoms and their degree by bathing in asthmatic patients. Methods A questionnaire focusing on ever experienced bathing-induced symptom changes and their degree, as well as contributing factors, was designed and administered to asthmatic patients in the outpatient department of our institute between January 2012 and November 2013. Results Two hundred fifteen cases were recruited. In 60 cases (27.9%), asthmatic symptoms appeared, including 20 cases of chest discomfort (33.3%), 19 cases of cough (31.7%), and 21 cases of wheezing (35.0%). The triggering factors included vapor inhalation (32 cases, 53.3%), hydrostatic pressure on the thorax due to body immersion in the bathtub (26 cases, 43.3%), and sudden change of air temperature (16 cases, 26.7%). Thirty-eight cases (17.7%) experienced improvement in active asthmatic symptoms by bathing. Vapor inhalation was the most common contributing factor (34 cases, 89.5%), followed by warming of the whole body (13 cases, 34.2%). There was no relationship between asthma severity and the appearance of bathing-induced symptoms or improvement of active asthmatic symptoms by bathing. Conclusion The effects of bathing in asthmatic patients widely differed from patient to patient and their etiology includes several factors. For those who suffer from bathing-induced asthma symptoms, preventive methods, such as premedication with bronchodilators before bathing, should be established. This study is registered in the University Hospital Medical Information Network (UMIN) clinical trials registry in Japan with the registration number UMIN000015641. PMID:27141485

  10. Inhibition of translation initiation factors might be the potential therapeutic targets for HCV patients with hepatic iron overload.

    PubMed

    Liu, Yiping; An, Daizhi; Sun, Rubao; Jin, Lianqun; Wang, Qiang

    2012-01-01

    Standard therapy, interferon-alpha (IFN-α) and ribavirin, remains the only available option for treatment of patients with hepatitis C virus (HCV) infection. However, iron overload, a common finding among HCV patients, have a poor response to treatment with current therapy. These data suggest that both host and viral factors are involved in the determination of the outcome of the therapy. Currently, novel antiviral compounds focus on the development of indirect antiviral drugs. The process of the viral translation is considered as the potential therapeutic targets. Coincidentally, study has found that hepatic iron load enhances the levels of eukaryotic initiation factor 3 (eIF3), which is essential for HCV translation. Reversely, iron chelation could reduce eIF3 p170 translation. Our hypothesis is that iron overload may specifically enhance cellular eIFs. As a result, the cellular mechanisms, in patients with iron overload, are utilized for translating viral mRNA into protein. Thus, treatment strategies that target eIFs should be an exceptionally good candidate therapeutic method for HCV patients with hepatic iron overload. PMID:22047986

  11. Effect of current exposure to Der p 1 on asthma symptoms, airway inflammation, and bronchial hyperresponsiveness in mite-allergic asthmatics.

    PubMed

    Alvarez, M J; Olaguibel, J M; Acero, S; García, B E; Tabar, A I; Urbiola, E

    2000-02-01

    The existence of a dose-response relationship between indoor allergen exposure and sensitization has been widely described, but the effect of allergen exposure on asthma activity (symptoms, bronchial hyperresponsiveness [BHR], and inflammation) is not clear. Our aim was to determine the existence of an association among current exposure to mite allergens and symptoms, BHR, and airway inflammation assessed in blood and sputum from asthmatic patients sensitized to Dermatophagoides pteronyssinus. We selected 31 mild and recently diagnosed (12-24 months) asthma patients sensitized to D. pteronyssinus. Allergenic exposure (Der p 1, Der 2) was assessed by a commercial assay based on monoclonal antibodies (mAb), carried out on the dust samples collected from patients' beds in a standardized way. Patients completed an asthma symptom questionnaire and underwent skin tests, methacholine bronchial challenge, and sputum induction. Sputum cell profile was analyzed and eosinophil cationic protein (ECP), tryptase, albumin, and interleukin(IL)-5 levels were quantified in sputum supernatant. Total eosinophil numbers and ECP levels were measured in blood samples. Most patients were exposed to Der p 1 levels under 2 microg/g of dust. Der p 1 exposure was higher among the subjects with positive sputum tryptase detection (P = 0.020). Der p 1 levels showed a trend toward correlation with asthma symptoms (P = 0.066, r = 0.36) and correlated with sputum tryptase levels (P = 0.032, r = 0.42). No relationship between BHR, eosinophilic inflammation, and allergenic exposure was found. Our results suggest that asthma symptoms and lung mast-cell activation are at least partially dependent on current allergen exposure. The lack of correlation between mite exposure, eosinophilic inflammation, and BHR supports the role of other factors that enhance the immunologic response initiated by allergen, increasing the activity of asthma. PMID:10726735

  12. Air Pollution and Acute Respiratory Response in a Panel of Asthmatic Children along the U.S.–Mexico Border

    PubMed Central

    Raysoni, Amit U.; Li, Wen-Whai; Holguin, Fernando; Johnson, Brent A.; Luevano, Silvia Flores; Garcia, Jose Humberto

    2011-01-01

    Background: Concerns regarding the health impact of urban air pollution on asthmatic children are pronounced along the U.S.–Mexico border because of rapid population growth near busy border highways and roads. Objectives: We conducted the first binational study of the impacts of air pollution on asthmatic children in Ciudad Juarez, Mexico, and El Paso, Texas, USA, and compared different exposure metrics to assess acute respiratory response. Methods: We recruited 58 asthmatic children from two schools in Ciudad Juarez and two schools in El Paso. A marker of airway inflammation [exhaled nitric oxide (eNO)], respiratory symptom surveys, and pollutant measurements (indoor and outdoor 48-hr size-fractionated particulate matter, 48-hr black carbon, and 96-hr nitrogen dioxide) were collected at each school for 16 weeks. We examined associations between the pollutants and respiratory response using generalized linear mixed models. Results: We observed small but consistent associations between eNO and numerous pollutant metrics, with estimated increases in eNO ranging from 1% to 3% per interquartile range increase in pollutant concentrations. Effect estimates from models using school-based concentrations were generally stronger than corresponding estimates based on concentrations from ambient air monitors. Both traffic-related and non–traffic-related particles were typically more robust predictors of eNO than was nitrogen dioxide, for which associations were highly sensitive to model specification. Associations differed significantly across the four school-based cohorts, consistent with heterogeneity in pollutant concentrations and cohort characteristics. Models examining respiratory symptoms were consistent with the null. Conclusions: The results indicate adverse effects of air pollution on the subclinical respiratory health of asthmatic children in this region and provide preliminary support for the use of air pollution monitors close to schools to track exposure and

  13. The early asthmatic response is associated with glycolysis, calcium binding and mitochondria activity as revealed by proteomic analysis in rats

    PubMed Central

    2010-01-01

    Background The inhalation of allergens by allergic asthmatics results in the early asthmatic response (EAR), which is characterized by acute airway obstruction beginning within a few minutes. The EAR is the earliest indicator of the pathological progression of allergic asthma. Because the molecular mechanism underlying the EAR is not fully defined, this study will contribute to a better understanding of asthma. Methods In order to gain insight into the molecular basis of the EAR, we examined changes in protein expression patterns in the lung tissue of asthmatic rats during the EAR using 2-DE/MS-based proteomic techniques. Bioinformatic analysis of the proteomic data was then performed using PPI Spider and KEGG Spider to investigate the underlying molecular mechanism. Results In total, 44 differentially expressed protein spots were detected in the 2-DE gels. Of these 44 protein spots, 42 corresponded to 36 unique proteins successfully identified using mass spectrometry. During subsequent bioinformatic analysis, the gene ontology classification, the protein-protein interaction networking and the biological pathway exploration demonstrated that the identified proteins were mainly involved in glycolysis, calcium binding and mitochondrial activity. Using western blot and semi-quantitative RT-PCR, we confirmed the changes in expression of five selected proteins, which further supports our proteomic and bioinformatic analyses. Conclusions Our results reveal that the allergen-induced EAR in asthmatic rats is associated with glycolysis, calcium binding and mitochondrial activity, which could establish a functional network in which calcium binding may play a central role in promoting the progression of asthma. PMID:20691077

  14. No effect of elevated operating lung volumes on airway function during variable workrate exercise in asthmatic humans.

    PubMed

    Klansky, Andrew; Irvin, Charlie; Morrison-Taylor, Adriane; Ahlstrand, Sarah; Labrie, Danielle; Haverkamp, Hans Christian

    2016-07-01

    In asthmatic adults, airway caliber fluctuates during variable intensity exercise such that bronchodilation (BD) occurs with increased workrate whereas bronchoconstriction (BC) occurs with decreased workrate. We hypothesized that increased lung mechanical stretch would prevent BC during such variable workrate exercise. Ten asthmatic and ten nonasthmatic subjects completed two exercise trials on a cycle ergometer. Both trials included a 28-min exercise bout consisting of alternating four min periods at workloads equal to 40 % (Low) and 70% (High) peak power output. During one trial, subjects breathed spontaneously throughout exercise (SVT), such that tidal volume (VT) and end-inspiratory lung volume (EILV) were increased by 0.5 and 0.6 liters during the high compared with the low workload in nonasthmatic and asthmatic subjects, respectively. During the second trial (MVT), VT and EILV were maintained constant when transitioning from the high to the low workload. Forced exhalations from total lung capacity were performed during each exercise workload. In asthmatic subjects, forced expiratory volume 1.0 s (FEV1.0) increased and decreased with the increases and decreases in workrate during both SVT (Low, 3.3 ± 0.3 liters; High, 3.6 ± 0.2 liters; P < 0.05) and MVT (Low, 3.3 ± 0.3 liters; High, 3.5 ± 0.2 liters; P < 0.05). Thus increased lung stretch during MVT did not prevent decreases in airway caliber when workload was reduced. We conclude that neural factors controlling airway smooth muscle (ASM) contractile activity during whole body exercise are more robust determinants of airway caliber than the ability of lung stretch to alter ASM actin-myosin binding and contraction. PMID:27150833

  15. Correlation of c-fos protein expression with neuropeptide content in the lung of bronchial asthmatic rat

    PubMed Central

    Liu, Haiyan; Yang, Xudong; Hou, Wei

    2014-01-01

    Objective: To investigate and analyze the correlation between the c-fos protein expression and neuropeptide content in the lung of bronchial asthmatic rats. Methods: Thirty-two (32) SD rats were randomly allocated into 4 groups of the normal control, the non-acute asthma, the acute asthma and the dexamethasone intervention. Immunohistochemistry was performed for histological observation, and substance P (SP) and vasoactive intestinal peptide (VIP) concentrations in the bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA). Results: SP concentration in the alveolar lavage of asthmatic rat was significantly higher than that in the normal control group (P < 0.0001), whereas VIP concentra