Sputum

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Sputum

  • induced sputum

  • Terms modified by Sputum

  • sputum cell
  • sputum cell count
  • sputum culture
  • sputum cytology
  • sputum eosinophil
  • sputum eosinophil count
  • sputum eosinophilia
  • sputum induction
  • sputum production
  • sputum sample
  • sputum specimen

  • Selected Abstracts


    Study of human metapneumovirus-associated lower respiratory tract infections in Egyptian adults

    MICROBIOLOGY AND IMMUNOLOGY, Issue 11 2009
    Maysaa El Sayed Zaki
    ABSTRACT There is a deficiency in the data concerning the role of hMPV in lower respiratory tract infections in adults, and until now there has been no data available regarding the prevalence of hMPV in adults in our region. In the present study the association of hMPV with varieties of lower respiratory tract disorders in immunocompetent adult patients, either alone or with bacterial pathogens, has been highlighted. Eighty-eight patients were included in the study. They included 46 males and 42 females with an age range of 38,65 years. Patients presented with lower respiratory tract infections associated with acute exacerbation of asthma (67%), pneumonia (17%), and acute exacerbation of chronic obstructive lung diseases. Sputum and nasopharyngeal samples were obtained from the patients and subjected to a full microbiological study. In addition, detection of hMPV was performed by nested reverse transcriptase polymerase chain reaction. The pathogens isolated were Streptococcus pneumoniae 46.6%, Staphylococci aureus 35.2%, and human metapneumovirus 13.6%. Influenza virus and rhinovirus were each isolated from 4.5% of patients. Human metapneumovirus was associated with S. pneumoniae in 4.5% in studied patients, while in 9.1% it was the only pathogen found in those patients. The commonest clinical condition with significant association with human metapneumovirus was pneumonia. The clinical and laboratory studies demonstrated an association between lower respiratory tract infections in adults and hMPV either as sole pathogen or in association with Streptococcus pneumoniae. It was a common pathogen in community-acquired pneumonia. [source]


    Antibody response to Pseudomonas aeruginosa in children with cystic fibrosis

    PEDIATRIC PULMONOLOGY, Issue 4 2009
    Lucimar G. Milagres PhD
    Abstract Cystic fibrosis (CF) is the most frequent life threatening autosomal recessive disease in white subjects. The primary cause of morbidity and mortality in children with CF is chronic pulmonary infection, mainly caused by Pseudomonas aeruginosa. The purpose of this study was to assess the value of the measurement of antibodies to P. aeruginosa in diagnosing lung infection by the bacteria in CF patients. We assessed P. aeruginosa antibody titers in CF patients from Rio de Janeiro, Brazil, using cell lysate antigens as well as recombinant PcrV, a Type III Secretion System protein. Sputum (more than 70% of the specimens) or oropharyngeal swabs were obtained whenever patients were regularly followed for their pulmonary disease. Blood samples were obtained with an average interval of 6 months for a period of 2 years. The ELISA cut-offs were assigned as the positive 95% confidence interval of the mean antibody levels from non-fibrocystic controls. Our data showed that most CF patients (81%) of whom were not chronically infected by P. aeruginosa (Groups I and II), had their first serology positive for rPcrV. Cell-lysate ELISA was able to detect P. aeruginosa antibodies before positive culture in the first serum sample of 44% of the patients from Groups I and II. When serum reactivity to rPcrV and cell lysate were combined, 94% of CF patients from Groups I and II (n,=,16) had the first serology positive for P. aeruginosa over a mean time of 20 months before the first isolation of P. aeruginosa. In conclusion, longitudinal P. aeruginosa serology should become part of respiratory care follow-up, in conjunction with other lung parameter functions. Pediatr Pulmonol. 2009; 44:392,401. © 2009 Wiley-Liss, Inc. [source]


    Sputum induction as a diagnostic tool for community-acquired pneumonia in infants and young children from a high HIV prevalence area

    PEDIATRIC PULMONOLOGY, Issue 1 2003
    H.J. Zar MD
    Abstract Sputum induction is a standard diagnostic procedure to identify pathogens in lower respiratory tract secretions in adults with pneumonia, but has rarely been studied or used in infants and young children. Our aim was to determine the usefulness of induced sputum (IS) as a diagnostic method for infants and children hospitalized with community-acquired pneumonia (CAP) in a high HIV prevalence area. Children hospitalized for CAP were prospectively enrolled over a year. IS was obtained by nebulization with hypertonic (5%) saline, physiotherapy, and suctioning. Sputum was submitted for bacterial and mycobacterial culture and P. carinii detection. Gastric lavages (GLs) were done for M. tuberculosis culture; a nasopharyngeal aspirate (NPA) was obtained for bacterial culture and P. carinii detection. IS was obtained in 210 children (median age, 7 (25th to 75th percentile, 3,18) months); 138 (66%) were HIV-infected; 148 (70%) were receiving supplemental oxygen. Bacteria were isolated from 101 (50%) IS and 141 (70%) NPA paired specimens (P,<,0.001). A significantly higher rate of S. aureus, H. influenzae, M. catarrhalis, and S. pneumoniae was found in NPAs compared to IS; this pattern was particularly evident in HIV-infected children. M. tuberculosis was cultured from sputum in 19 patients (9%); GLs performed in 142 children were positive in only 9 (6%). The difference (95% confidence interval) between yields for M. tuberculosis from culture of IS compared to GL was 4.3% (95% CI, 0,5.6%; P,=,0.08). P. carinii was identified from IS in 12 (5.7%) children; all corresponding NPAs were negative. Seven (3%) children could not tolerate sputum induction. Side effects included increased coughing in 4%, epistaxis in 3%, and wheezing responsive to bronchodilators in 1%. In conclusion, induced sputum is a useful and safe diagnostic procedure in infants and children with CAP from a high HIV prevalence area. Pediatr Pulmonol. 2003; 36:58,62. © 2003 Wiley-Liss, Inc. [source]


    Relationship between induced sputum cytology and inflammatory status with lung structural and functional abnormalities in asbestosis

    AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 3 2008
    José Henrique Setta MD
    Abstract Background Asbestosis is associated with lung cellular and immunological abnormalities. Induced sputum cytology and local and systemic markers of inflammation may be helpful to characterize disease status and progression in these patients. Methods Thirty-nine ex-workers with asbestosis on high-resolution CT (HRCT) and 21 non-exposed controls were evaluated. Sputum cytology and IL-8 in serum and sputum were related to lung function impairment. Results Subjects with asbestosis had reduced sputum cellularity but higher macrophage/neutrophil ratio and % macrophage as compared with controls. Sputum and serum IL-8 were also higher in patients with asbestosis (P,<,0.05). In addition, evidence of lung architectural distorption on HRCT was associated with increased levels of serum IL-8. Interestingly, absolute macrophage number was negatively correlated with total lung capacity (r,=,,0.40; P,=,0.04) and serum IL-8 to lung diffusing capacity (r,=,,0.45; P,=,0.01). Conclusions Occupationally exposed subjects with asbestosis on HRCT have cytologic abnormalities in induced sputum and increased local and systemic pro-inflammatory status which are correlated to functional impairment. Am. J. Ind. Med. 51:186,194, 2008. © 2008 Wiley-Liss, Inc. [source]


    Sputum carcinoembryonic antigen, neuron-specific enolase and cytokeratin fragment 19 levels in lung cancer diagnosis

    RESPIROLOGY, Issue 1 2004
    Ioannis Kalomenidis
    Objective: The aim of the present study was to examine the impact of sputum carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and cytokeratin fragment 19 (CYFRA 21-1) levels in lung cancer diagnosis and to compare the diagnostic usefulness of sputum assays with that of serum assays. Methodology: Forty-seven patients with lung cancer and 62 with benign lung disease were studied. Tumour marker levels in sputum (sp.) and serum (ser) were measured by immunoradiometric assays. Results: Sputum and serum tumour marker levels were significantly higher in lung cancer than in benign disease. When the specificity was 95%, the sensitivity was 57%, 43%, 36%, 30%, 28% and 19%, for spCEA, serCYFRA 21-1, spCYFRA 21-1, serCEA, serNSE, and spNSE, respectively. Bayesian analysis showed that the best predictive values correspond to spCEA and serCYFRA 21-1. The maximum overall gain was obtained in pretest probability of 0.35 for both spCEA and serCYFRA 21-1, with predictive values of 84% and 80% for spCEA and serCYFRA 21-1, respectively. Conclusion: Sputum tumour marker levels were no more useful than the serum levels in lung cancer diagnosis. SpCEA offered the best predictive values but these were still not sufficiently satisfactory for spCEA to be proposed for routine use. [source]


    Inhaled allergen-driven CD1c up-regulation and enhanced antigen uptake by activated human respiratory-tract dendritic cells in atopic asthma

    CLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2007
    N. E. McCarthy
    Summary Background Dendritic cells (DC) mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory-tract DC (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD1 antigen presentation by hRTDC may contribute to asthma pathogenesis. Objective To investigate the influence of hRTDC on the balance between atopy and allergic asthma in human subjects and to determine whether CD1 expression by hRTDC is modulated during asthmatic inflammation. Methods Sputum cells were induced from steroid-naïve, allergen-challenged and allergen-naïve subjects (atopic asthmatics, atopic non-asthmatics and non-atopic controls). hRTDC were identified using monoclonal antibody labelling and analysis by flow cytometry. Results hRTDC stained HLA-DR+ (negative for markers of other cell lineages) were predominantly myeloid and comprised ,0.5% of viable sputum cells. Sputum cells were potent stimulators of allogeneic CD4+ naïve T cells and enrichment/depletion experiments correlated stimulatory potency with DC numbers. Sputum contained cells that exhibited typical dendritic morphology when analysed by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of FITC-dextran was enhanced in cells from asthmatics (P<0.001). Despite their increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and expressed increased levels of maturation markers (P<0.05,P<0.001), CD1c, CD1d and langerin (P<0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon in vivo allergen challenge (three to ninefold within 24 h; P<0.05). CD11c,CD123high hRTDC were only detected in asthmatic sputum and were increased in number following allergen challenge. Conclusion Despite limited cell numbers, it proved possible to analyse human RTDC in induced sputum, providing evidence that increased antigen uptake and enhanced CD1 presentation by activated hRTDC may contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma may therefore constitute a novel target for future intervention strategies. [source]


    Effect of a 4-week treatment with theophylline on sputum eosinophilia and sputum eosinophil chemotactic activity in steroid-naive asthmatics

    CLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2000
    Louis
    Background The precise mechanism of action of theophylline in asthma is not fully understood but recent data have drawn attention to its potential anti-inflammatory effect. Objective The purpose of this study was to assess the effect of theophylline on sputum eosinophilia and sputum eosinophil chemotactic activity in steroid-naive asthmatics. Method We performed a 4-week randomized double-blind, placebo-controlled, parallel group study in 21 mild to moderate steroid-naive asthmatics whose sputum eosinophilia was found twice > 5% during the run in period. Eleven subjects received 600 mg/24 h theophylline for the first 2 weeks and 900 mg/24 h for the last 2 weeks while 10 subjects took a placebo for 4 weeks. Sputum was induced after 2 and 4 weeks of treatment and 1 week after stopping the treatment. The sputum samples were compared for their cell counts, eosinophil cationic protein (ECP) levels and eosinophil chemotactic activity using micro-Boyden chambers. Results Serum theophylline concentrations reached 7 and 11 ,g/mL at V3 and V4, respectively. Intragroup comparisons showed that theophylline, but not placebo, caused a significant reduction in sputum eosinophil counts at V3 (62 ± 10% from baseline, P < 0.01) and a strong trend at V4 (67 ± 16% from baseline, P = 0.07) when compared to baseline. The intergroup difference obtained after comparing the area under the curve over the 4 week treatment period only approached the statistical significance (P = 0.08). At baseline the fluid phase of the sputum contained a significant eosinophil chemotactic activity which was inhibited after a 4-week treatment by theophylline (P < 0.01) but not by placebo. The mean sputum theophylline levels after 4 weeks of treament (1.7 ,g/mL) was lower than that required to cause significant inhibition of eosinophil chemotaxis in vitro. Conclusion Theophylline decreases the natural sputum eosinophil chemotactic activity present in asthmatics. However, when using a small sample size, the 35% reduction in sputum eosinophilia achieved by theophylline failed to reach statistical significance when compared to that seen after placebo. [source]


    The BSCC Code of Practice , exfoliative cytopathology (excluding gynaecological cytopathology)

    CYTOPATHOLOGY, Issue 4 2009
    A. Chandra
    Exfoliative cytopathology (often referred to as non-gynaecological cytology) is an important part of the workload of all diagnostic pathology departments. It clearly has a role in the diagnosis of neoplastic disease but its role in establishing non-neoplastic diagnoses should also be recognised. Ancillary tests may be required to establish a definitive diagnosis. Clinical and scientific teamwork is essential to establish an effective cytology service and staffing levels should be sufficient to support preparation, prescreening, on-site adequacy assessment and reporting of samples as appropriate. Routine clinical audit and histology/cytology correlation should be in place as quality control of a cytology service. Cytology staff should be involved in multidisciplinary meetings and appropriate professional networks. Laboratories should have an effective quality management system conforming to the requirements of a recognised accreditation scheme such as Clinical Pathology Accreditation (UK) Ltd. Consultant pathologists should sign out the majority of exfoliative cytology cases. Where specimens are reported by experienced biomedical scientists (BMS), referred to as cytotechnologists outside the UK, this must only be when adequate training has been given and be defined in agreed written local protocols. An educational basis for formalising the role of the BMS in exfoliative cytopathology is provided by the Diploma of Expert Practice in Non-gynaecological Cytology offered by the Institute of Biomedical Science (IBMS). The reliability of cytological diagnoses is dependent on the quality of the specimen provided and the quality of the preparations produced. The laboratory should provide feedback and written guidance on specimen procurement. Specimen processing should be by appropriately trained, competent staff with appropriate quality control. Microscopic examination of preparations by BMS should be encouraged wherever possible. Specific guidance is provided on the clinical role, specimen procurement, preparation and suitable staining techniques for urine, sputum, semen, serous cavity effusion, cerebrospinal fluid, synovial fluid, cyst aspirates, endoscopic specimens, and skin and mucosal scrapes. [source]


    Brushing, sputum, bronchoalveolar lavage and imprint cytology in the Churg,Strauss Syndrome

    CYTOPATHOLOGY, Issue 3 2003
    L'. Babjaková
    No abstract is available for this article. [source]


    Aspiration biopsy cytomorphology of primary pulmonary germ cell tumor metastatic to the brain

    DIAGNOSTIC CYTOPATHOLOGY, Issue 10 2009
    Haitham Arabi M.D.
    Abstract Extragonadal germ cell tumors are uncommon and such tumors originating from the lung parenchyma are extremely rare. This is a case of 68-year-old female who was admitted with complaints of right-sided weakness, inability to maintain her balance, right-sided headache, and bloody sputum. Her workup revealed two enhancing brain lesions and large lung mass involving the left lower lobe. Fine-needle aspiration (FNA) of the lung followed by craniotomy was performed and the patient was initially diagnosed with lung adenocarcinoma metastatic to the brain based on the cytomorphology of the lung FNA and histology of the brain mass. However, retrospective investigation revealed markedly elevated alpha fetoprotein (AFP) of which the cytopathologist was unaware at the time of diagnosis. A review of the cytology and surgical specimen slides, as well as immunohistochemistry (IHC) on the brain tumor and FNA cell block were preformed. On the basis of the slides review, clinical findings, and immunostaining results, a diagnosis of primary pulmonary mixed germ cell tumor, containing choriocarcinoma and yolk sac elements, with brain metastases, was retrospectively made. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source]


    Simultaneous cytological diagnosis of herpes simplex virus infection and primary lung cancer: Report of two cases

    DIAGNOSTIC CYTOPATHOLOGY, Issue 11 2008
    Nicoletta Maounis M.D., Ph.D.
    Abstract Herpes simplex is an uncommon cause of lower respiratory tract infection that requires prompt diagnosis and treatment to prevent late complications. We report two cases with simultaneous herpes simplex virus infection of the lower respiratory tract and lung carcinoma. Cytology of bronchial brushing and washing fluids and postbronchoscopic sputum established the diagnosis, which was further corroborated by real-time polymerase chain reaction. Diagn. Cytopathol. 2008;36:818,822. © 2008 Wiley-Liss, Inc. [source]


    Exfoliative sputum cytology of cancers metastatic to the lung,

    DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2005
    Tehmina Z. Ali M.D.
    Abstract Although largely replaced by fine-needle aspiration (FNA) and bronchoscopy, cytological examination of sputum for exfoliated malignant cells still is considered a valuable initial diagnostic test in patients presenting with a lung mass. Thirty-five cases of secondary/metastatic tumors involving the lung and diagnosed on sputum were retrospectively reviewed from our cytopathology files for a period of 22 yr (1980,2001). Clinical history and the relevant histopathological material were examined and correlated with the cytological findings. In all cases, a history of malignancy was known. Cytological diagnoses included colonic adenocarcinoma (7 cases); non-Hodgkin's lymphoma (NHL; 5 cases); malignant melanoma (MM; 5 cases); breast carcinoma (5 cases); Hodgkin's lymphoma (HL; 3 cases); pancreatic adenocarcinoma (2 cases); prostatic adenocarcinoma (2 cases); and 1 case each of urothelial carcinoma, endometrial carcinoma, renal cell carcinoma, hepatic small-cell carcinoma, squamous-cell carcinoma (cervix), and leiomyosarcoma (LMS). Cellular preservation was optimal in all cases. The smear background was relatively clean in 25 (71%) cases and predominantly inflamed and/or necrotic in 10 (29%) cases. In non-lymphoid tumors (27 cases), isolated single malignant cells were seen in 7 (26%) cases (all cases of MM and prostatic adenocarcinoma), whereas 20 (74%) cases displayed fragments with intact tumor architecture. Overall, only 10/35 (29%) cases showed noticeable tumor-cell necrosis. In one case (LMS), cell block sections were used for immunoperoxidase (IPOX) studies with positive staining for desmin and actin. Exfoliation of cancer cells in sputum from secondary tumors in the lung is a rare phenomenon in current-day practice, with metastatic colonic adenocarcinoma seen most commonly. Intact tumor architecture was observed in exfoliated cells in 75% of the cases. Diagn. Cytopathol. 2005;33:147,151. © 2005 Wiley-Liss, Inc. [source]


    Human airway trypsin-like protease induces amphiregulin release through a mechanism involving protease-activated receptor-2-mediated ERK activation and TNF ,-converting enzyme activity in airway epithelial cells

    FEBS JOURNAL, Issue 24 2005
    Manabu Chokki
    Human airway trypsin-like protease (HAT), a serine protease found in the sputum of patients with chronic airway diseases, is an agonist of protease-activated receptor-2 (PAR-2). Previous results have shown that HAT enhances the release of amphiregulin (AR); further, it causes MUC5AC gene expression through the AR-epidermal growth factor receptor pathway in the airway epithelial cell line NCI-H292. In this study, the mechanisms by which HAT-induced AR release can occur were investigated. HAT-induced AR gene expression was mediated by extracellular signal-regulated kinase (ERK) pathway, as pretreatment of cells with ERK pathway inhibitor eliminated the effect of HAT on AR mRNA. Both HAT and PAR-2 agonist peptide (PAR-2 AP) induced ERK phosphorylation; further, desensitization of PAR-2 with a brief exposure of cells to PAR-2 AP resulted in inhibition of HAT-induced ERK phosphorylation, suggesting that HAT activates ERK through PAR-2. Moreover, PAR-2 AP induced AR gene expression subsequent to protein production in the cellular fraction through the ERK pathway indicating that PAR-2-mediated activation of ERK is essential for HAT-induced AR production. However, in contrast to HAT, PAR-2 AP could not cause AR release into extracellular space; it appears that activation of PAR-2 is not sufficient for HAT-induced AR release. Finally, HAT-induced AR release was eliminated by blockade of tumour necrosis factor ,-converting enzyme (TACE) by the TAPI-1 and RNA interference, suggesting that TACE activity is necessary for HAT-induced AR release. These observations show that HAT induces AR production through the PAR-2 mediated ERK pathway, and then causes AR release by a TACE-dependent mechanism. [source]


    Trends in fungal colonization of pancreatic necrosis in patients undergoing necrosectomy for acute pancreatitis

    HPB, Issue 2 2005
    N. K. K. KING
    Abstract Background. This study examines fungal colonization of post-inflammatory pancreatic necrosis in a cohort of patients undergoing open surgical necrosectomy in a single, tertiary referral unit over a 10-year period. Methods. The charts of all patients with acute pancreatitis who underwent surgical necrosectomy during the period January 1992 to December 2001 were examined. Following exclusions a population of 30 patients were identified. There were 18 men with a median (range) age of 42 (20,69) years. Sixteen (53%) underwent surgery because of positive fine needle aspirates and the remainder underwent surgery on clinical grounds. Twenty-nine (97%) received antibiotics prior to necrosectomy. Principal outcomes were the results of microbiological culture with reference to isolation of fungi, site of isolates, trends in colonization and outcome. Results. Candida were cultured from pancreatic necrosis in 5 (17%). These 5 individuals also had positive candidal cultures from sputum or bronchial aspirates. There were no deaths in patients with fungal colonization of necrosis. There was no change in the annual incidence of fungal colonization of necrosis over the study period. Conclusion. Although this is a small study, there are two consistent observations: mortality in fungal colonization of necrosis was low and there was no change in the annual incidence of fungal colonization of necrosis over the decade. Discrepancies between these findings and those of previous reports mandate larger prospective evaluation. [source]


    Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: A nested case,control study

    INTERNATIONAL JOURNAL OF CANCER, Issue 5 2006
    Rosalia Cirincione
    Abstract We evaluated the aberrant promoter methylation profile of a panel of 3 genes in DNA from tumor and sputum samples, in view of a complementary approach to spiral computed tomography (CT) for early diagnosis of lung cancer. The aberrant promoter methylation of RAR,2, p16INK4A and RASSF1A genes was evaluated by methylation-specific PCR in tumor samples of 29 CT-detected lung cancer patients, of which 18 had tumor-sputum pairs available for the analysis, and in the sputum samples from 112 cancer-free heavy smokers enrolled in a spiral CT trial. In tumor samples from 29 spiral CT-detected patients, promoter hypermethylation was identified in 19/29 (65.5%) cases for RAR,2, 12/29 (41.4%) for p16INK4A and 15/29 (51.7%) for RASSF1A. Twenty-three of twenty-nine (79.3%) samples of the tumors exhibited methylation in at least 1 gene. In the sputum samples of 18 patients, methylation was detected in 8/18 (44.4%) for RAR,2 and 1/18 (5%) for both RASSF1A and p16INK4A. At least 1 gene was methylated in 9/18 (50%) sputum samples. Promoter hypermethylation in sputum from 112 cancer-free smokers was observed in 58/112 (51.7%) for RAR,2 and 20/112 (17.8%) for p16, whereas methylation of the RASSF1A gene was found in only 1/112 (0.9%) sputum sample. Our study indicates that a high frequency of hypermethylation for RAR,2, p16INK4A and RASSF1A promoters is present in spiral CT-detected tumors, whereas promoter hypermethylation of this panel of genes in uninduced sputum has a limited diagnostic value in early lung cancer detection. © 2005 Wiley-Liss, Inc. [source]


    Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers

    INTERNATIONAL JOURNAL OF CANCER, Issue 4 2003
    Sabine Zöchbauer-Müller
    Abstract An important method for silencing tumor suppressor genes in cancers is by aberrant methylation (referred to as methylation) of CpG islands in gene promoter regions. In lung cancer, methylation of the genes retinoic acid receptor ,-2 (RAR,- 2), CDH13 (H-cadherin), p16INK4a (p16), RASSF1A (RAS association domain family I) is frequent. Thus, we investigated methylation of these genes in 4 different types of specimens (oropharyngeal brushes, sputum samples, bronchial brushes and bronchioloalveolar lavage [BAL] samples) of the upper aerodigestive tract epithelium from heavy smokers without evidence of cancer but with morphometric evidence of sputum atypia and compared the frequencies of methylation in the different types of specimens. In addition, we also analyzed sputum samples from 30 never smokers for methylation of these genes. Our major findings are: (i) At least one gene was methylated in one or more specimens from 48% of the smokers. However, methylation was statistically significant less frequently in never smokers compared to smokers. (ii) In general, methylation occurred more frequently in samples from the central airways (sputum, bronchial brushes) compared to the peripheral airways (BAL) and only occasionally in the oropharynx. (iii) RAR,- 2 was the most frequently methylated gene, whereas the frequency of methylation for the other genes was lower. (iv) Data from sputum samples and bronchial brushes were comparable. Our findings suggest that detection of methylation should be investigated as an intermediate marker for lung cancer risk assessment and response to chemopreventive regimens. © 2003 Wiley-Liss, Inc. [source]


    Uncommon skin lesion in a patient with ataxia-telangiectasia

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2008
    Chinedu Ivonye MD
    A 20-year-old African-American man, with a history of ataxia-telangiectasia diagnosed at the age of one year, presented to the hospital with fever, cough, and headache of 2 days' duration. The fever was of high grade, associated with chills and rigors. The headache was frontal in location, constant, pounding in nature, and associated with photophobia and phonophobia; there was no neck pain, no neck stiffness, and no blurring of vision. The patient complained of facial pain. There were no relieving or aggravating factors. The family denied any change in mental status. ,The cough was productive of yellowish sputum. There was associated rhinorrhea. The patient complained of nausea and vomiting with the headache. A review of other systems was negative. ,On presentation in the emergency room, the patient was tachypneic, febrile, and tachycardic. He was oriented to time, place, and person. His neck was supple and meningeal signs were negative. He had maxillary sinus tenderness. Neurologic examination revealed nystagmus, ocular telangiectasia (Fig. 1), ataxia, and globally decreased muscle strength. Skin examination showed hypopigmented areas on all four extremities, the face, and neck (Figs 1,4), without involvement of the trunk. The rest of the physical examination was unremarkable. Figure 1. Area of vitiligo on the neck with premature graying of the hair Figure 2. Vitiligo on the hands Figure 3. Vitiligo involving the legs Figure 4. Ocular telangiectasia ,The leukocyte count was elevated at 19,600/mcL, with a differential of neutrophils (84%), monocytes (11%), and lymphocytes (5%). Hemoglobin and hematocrit were normal. Chemistry and chest X-ray were normal. ,Computed tomography scan of the head showed acute sinusitis and cerebellar atrophy consistent with ataxia-telangiectasia. ,A lumbar puncture was performed, and cerebrospinal fluid findings were suggestive of aseptic meningitis. ,The patient was treated for aseptic meningitis and acute sinusitis with acyclovir and ceftriaxone. The leukocyte count normalized, the patient remained afebrile, and was asymptomatic after 2 days of treatment with antimicrobials. The rest of the hospital stay was uneventful. [source]


    Cutaneous sarcoid-like granulomas with alveolar hemorrhage and c-ANCA PR-3

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2004
    Natividade Rocha MD
    A 28-year-old woman, employed as a leather factory worker, noted asymptomatic, well-delimited plaques on both knees, 6 years ago. The plaques were violaceous with a smooth surface. One appeared over a post-traumatic scar from childhood (Fig. 1). Two years later, she began to complain of symptoms suggestive of polyarthritis, first of the small joints of the hands (proximal interphalanges) and then of the larger joints (wrists, elbows, and knees). She was diagnosed with rheumatoid arthritis and began treatment with nonsteroidal anti-inflammatory drugs for 1 month without any change. Deflazacort, 12 mg/day, and hydroxychloroquine, 400 mg/day, were administered for 3 months, with improvement of her articular complaints, but not her skin lesions. Figure 1. Well-delimited, violaceous plaques with a smooth surface on the knees, one over an old post-traumatic scar One year later, she complained of dysphonia, which remitted spontaneously after some weeks. After one additional year, she noted papules, with similar characteristics to the plaques, on the elbows, and two well-delimited orange-to-brown plaques on the forehead (Fig. 2). Figure 2. Orange,brown plaques symmetrically placed on the forehead During the fifth year of the disease, she was referred for the first time to a dermatologist, who biopsied one of the knee lesions. The histologic result was compatible with "sarcoid granuloma." At that time, she presented with skin lesions as her only complaint. Sarcoidosis was suspected based on a chest X-ray, which revealed hilar lymphadenopathy and diffuse accentuation of the interstitium. In November 2000, she suddenly developed fever (40 °C), cough with hemoptysis, dysphonia, and subcutaneous nodules on the palmar surface of the fingers of both hands that were painless, well-delimited, 5 mm in diameter, and firm (Fig. 3). She reported a weight loss of 12 kg in the previous 3 months. Pulmonary condensation was found on auscultation, and she had palpable hepatomegaly. Peripheral lymphadenopathy was not present. Figure 3. Painless, well-delimited, firm subcutaneous nodules on the palmar surface of the fingers Laboratory investigations revealed normochromic, normocytic anemia (hemoglobin, 7.7 g/dL), iron deficit, a white blood cell count of 16,000/µL with neutrophilia, an erythrocyte sedimentation rate of 130 mm/h, elevation of liver enzymes, a slight increase in angiotensin-converting enzyme (ACE) level (72 U/L), hypergammaglobulinemia (IgG, 3350 mg/dL), antinuclear antibody (ANA) of 1 : 320, and a slight increase in CD4 and decrease in CD8 lymphocytes with normal cellular morphology in blood. Renal function, urine sediment, urine and serum calcium, complement (C4), dsDNA, antimitochondrial antibody, direct and indirect Coombs test, antineutrophil cytoplasmic antibody (ANCA), tuberculin skin tests, viral markers of hepatitis B, C, and human immunodeficiency virus (HIV), electrocardiogram (ECG), ophthalmic examinations, and culture for infectious agents in blood and sputum were all normal or negative. Computed tomography (CT) scan showed an infiltrate in the upper right pulmonary lobule with a central cavity and bilateral hilar lymphadenopathy (Fig. 4). Homogeneous hepatosplenomegaly was present. The bronchoalveolar lavage (BAL) showed a slight lymphocytic increase predominantly of CD8 cells and hemosiderosis. Stains for infectious agents, including acid-fast bacillus, fungi, Mycoplasma, and Legionella, were negative. Three biopsies from the forehead, elbows, and knees showed well-formed noncaseating epithelioid cell granulomas with giant cells of the Langhans type in the dermis, suggestive of sarcoidosis (Figs 5 and 6). A fourth biopsy from a finger nodule demonstrated inflammatory infiltration of the dermis and necrosis with cellular debris. Vasculitis was not seen (Fig. 7). Figure 4. Computed tomography scan showing an infiltrate in the upper right pulmonary lobule with a central cavity Figure 5. Beneath a flattened epidermis, several sarcoid granulomas composed of epithelioid histiocytes and several multinucleated giant cells of Langhans type can be seen (hematoxylin and eosin, ×10) Figure 6. Less well-formed sarcoid granulomas in a hyperkeratotic area, surrounded by a sparse rim of lymphocytes (hematoxylin and eosin, ×20) Figure 7. Foci of necrosis and fibrinoid degeneration with some neutrophil infiltration and nuclear dusting (hematoxylin and eosin, ×40) The patient was treated with a broad-spectrum empirical antimicrobial (levofloxacin, 500 mg daily intravenously) over 12 days, with prompt improvement in her symptoms and remission of the forehead and finger lesions. Nevertheless, on the first evaluation after hospitalization, the CT scan showed persistence of the pulmonary cavity (Fig. 8). A repeat ANCA determination was positive (cytoplasmic pattern, c-ANCA) at 1 : 640 by indirect immunofluorescence (IIF). Antiproteinase-3 antibody was demonstrated at 78 by enzyme-linked immunosorbent assay (ELISA). Figure 8. Computed tomography scan showing persistence of the pulmonary cavity She underwent an open lung biopsy which revealed intra-alveolar hemorrhage and scanty noncaseating epithelioid cell granulomas of the sarcoidosis type in the peripheral blood vessels without vasculitis. A diagnosis of Wegener's granulomatosis was made and she began prednisolone (1 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day). One year later, she is asymptomatic, the skin lesions have completely remitted, c-ANCA is negative, and the CT scan shows partial regression of the pulmonary cavity. [source]


    Phenotypic study by numerical taxonomy of strains belonging to the genus Aeromonas

    JOURNAL OF APPLIED MICROBIOLOGY, Issue 1 2002
    L. Valera
    Aims: ,This study was undertaken to cluster and identify a large collection of Aeromonas strains. Methods and Results: ,Numerical taxonomy was used to analyse phenotypic data obtained on 54 new isolates taken from water, fish, snails, sputum and 99 type and reference strains. Each strain was tested for 121 characters but only the data for 71 were analysed using the `SSM' and `SJ' coefficients, and the UPGMA clustering algorithm. At SJ values of , 81·6% the strains clustered into 22 phenons which were identified as Aer. jandaei, Aer. hydrophila, Aer. encheleia, Aer. veronii biogroup veronii, Aer. trota, Aer. caviae, Aer. eucrenophila, Aer. ichthiosmia, Aer. sobria, Aer. allosaccharophila, Aer. media, Aer. schubertii and Aer. salmonicida. The species Aer. veronii biogroup sobria was represented by several clusters which formed two phenotypic cores, the first related to reference strain CECT 4246 and the second related to CECT 4835. A good correlation was generally observed among this phenotypic clustering and previous genomic and phylogenetic data. In addition, three new phenotypic groups were found, which may represent new Aeromonas species. Conclusions: ,The phenetic approach was found to be a necessary tool to delimitate and identify the Aeromonas species. Significance and Impact of the Study: ,Valuable traits for identifying Aeromonas as well as the possible existence of new Aeromonas species or biotypes are indicated. [source]


    Airway inflammation in subjects with gastro-oesophageal reflux and gastro-oesophageal reflux-related asthma

    JOURNAL OF INTERNAL MEDICINE, Issue 3 2006
    G. E. CARPAGNANO
    Abstract. Study objectives., Asthma and gastro-oesophageal reflux (GER) are both characterized by airway inflammation. Design., The purposes of this work were (i) to study airway inflammation in patients troubled by gastro-oesophageal reflux (GER) and GER associated with asthma, (ii) to ascertain whether GER can aggravate asthma by exacerbating the pre-existing airway inflammation and oxidative stress and (iii) to establish the validity of analysing breath condensate and induced sputum when studying the airways of subjects affected by GER. Patient s and methods., We enrolled 14 patients affected by mild asthma associated with GER (40 ±12 years), nine with mild but persistent asthma (39 ± 13 years), eight with GER (35 ± 11 years) and 17 healthy subjects (37 ± 9 years). Sputum cell counts and concentrations of interleukin-4 (IL-4), IL-6 and 8-isoprostane were measured in breath condensate and supernatant. Measurements and results., GER-related asthma is characterized by an eosinophilic inflammation, as determined by elevated concentrations of IL-4 in breath condensate and sputum supernatant, and by sputum cell analysis. GER alone presents a neutrophilic pattern of inflammation when determined by elevated concentrations of IL-6 in sputum cell analysis. A concomitant increase has been found in 8-isoprostane in GER associated (or not associated) with asthma. Conclusions., We conclude that GER is characterized by a neutrophilic airway inflammation and by increased oxidative stress. GER does not however aggravate pre-existing airway inflammation in asthma patients. Determinations of inflammatory and oxidant markers in the breath condensate of subjects with GER reflect these measured in the induced sputum. [source]


    DNA methylation: an epigenetic pathway to cancer and a promising target for anticancer therapy

    JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2002
    Jesper Worm
    Abstract The unique properties of a cancer cell are acquired through a stepwise accumulation of heritable changes in the information content of proto-oncogenes and tumor suppressor genes. While gain, loss, and mutation of genetic information have long been known to contribute to tumorigenesis, it has been increasingly recognized over the past 5 years that ,epigenetic' mechanisms may play an equally important role. The main epigenetic modification of the human genome is methylation of cytosine residues within the context of the CpG dinucleotide. De novo methylation of ,CpG islands' in the promoter regions of tumor suppressor genes may lead to transcriptional silencing through a complex process involving histone deacetylation and chromatin condensation, and thus represents a tumorigenic event that is functionally equivalent to genetic changes like mutation and deletion. DNA methylation is interesting from a diagnostic viewpoint because it may be easily detected in DNA released from neoplastic and preneoplastic lesions into serum, urine or sputum, and from a therapeutic viewpoint because epigenetically silenced genes may be reactivated by inhibitors of DNA methylation and/or histone deacetylase. A better understanding of epigenetic mechanisms leading to tumor formation and chemoresistance may eventually improve current cancer treatment regimens and be instructive for a more rational use of anticancer agents. [source]


    Rapid detection of Haemophilus influenzae by hel gene polymerase chain reaction

    LETTERS IN APPLIED MICROBIOLOGY, Issue 3 2003
    M.C. Yadav
    Abstract Aims: To evaluate the efficiency of hel gene polymerase chain reaction (PCR) to detect Haemophilus influenzae in various clinical/non-clinical samples. Methods and Results: Seventy-four clinical samples (cerebrospinal fluid, blood, sputum, throat and nasal swabs) and throat swabs of 17 asymptomatic carriers were collected. Primers were used to amplify the hel gene of H. influenzae encoding P4 outer membrane protein directly from the processed samples. The samples were also examined by conventional culture methods and the results were compared with those of PCR. The culture methods showed positive results in 60 (65·9%) of 91 samples in contrast to 62 (68·12%) samples tested positive by PCR. None of the culture-positive samples were PCR-negative while two of the culture-negative samples were PCR-positive. The specificity of the products was confirmed by Southern hybridization and failure of various other organisms to amplify the hel gene product. The sensitivity of the PCR assay was found to be 50 pg of DNA. Conclusions: These findings suggest that the hel gene PCR is a rapid, sensitive and a specific new method for direct identification of H. influenzae. Significance and Impact of the study: Thus, this PCR test can improve the detection rate of H. influenzae in suspected clinical samples as compared with that of conventional culture methods. [source]


    Cytokine production from sputum cells and blood leukocytes in asthmatics according to disease severity

    ALLERGY, Issue 7 2010
    M. Manise
    To cite this article: Manise M, Schleich F, Gusbin N, Godinas L, Henket M, Antoine N, Corhay JL, Louis R. Cytokine production from sputum cells and blood leukocytes in asthmatics according to disease severity. Allergy 2010; 65: 889,896. Abstract Background:, Although mild to moderate asthma is known to be Th2 driven, cytokines produced in refractory asthma might not fit the classical Th2 pattern. Methods:, The aim of our study was to assess the cytokine production by sputum and blood cells from 15 refractory asthmatics (American Thoracic Society Criteria) compared to 15 mild untreated and 17 moderate treated asthmatics and 22 healthy subjects. Spontaneous production of interleukin (IL)-4, IL-6, IL-10, interferon-,, and tumor necrosis factor , was measured by immunotrapping after 24 h sputum or blood cell culture. Results:, Moderate and refractory asthmatics were both characterized by a lower production of IL-6 from their airway cells compared to healthy subjects. However, the difference was no longer significant when expressing the results per gram of sputum. No significant difference between the three groups was found regarding other cytokines. As for cytokine production from blood, the three groups of asthmatics exhibited raised production of IL-4 when compared to healthy subjects, and this was true when results were expressed per blood volume or after normalization for total leukocyte cell count. Moderate asthmatics exhibited greater production of IL-10 when compared to refractory asthmatics and healthy subjects when results were normalized for total leukocyte cell count. Conclusions:, Sputum cells from moderate and refractory asthmatics release less IL-6. While the systemic overproduction of IL-4 was observed through the all spectrum of asthma severity, moderate asthmatics exhibited greater systemic IL-10 production compared to refractory asthmatics. [source]


    Matrix metalloproteinases, IL-8 and glutathione in the prognosis of workers exposed to chlorine

    ALLERGY, Issue 6 2010
    K. Maghni
    To cite this article: Maghni K, Malo J-L, L'Archevêque J, Castellanos L, Gautrin D. Matrix metalloproteinases, IL-8 and glutathione in the prognosis of workers exposed to chlorine. Allergy 2010; 65: 722,730. Abstract Background:, Workers exposed to chlorine may be at risk of deterioration in FEV1. Methods:, A prospective study of 72 workers examined over a 5.8 ± 1.9 year period. A sample of induced sputum for cells and mediators was obtained in 69 subjects at baseline (Vb) and in 36 both at Vb and at follow-up (Vf). Results:, Sixty-four workers (89%) experienced at least one accidental inhalation of chlorine in the interval. The mean decrease in FEV1 was 30 ml/year and thus was within normal limits. Among the analysed remodelling markers, the level of the MMP-9-TIMP-1 complex, but not of free MMP-9 and TIMP-1, significantly diminished from Vb to Vf. We found significant correlations between neutrophils, IL-8, MMP-9 and MMP9-TIMP-1 complex at Vb and Vf. While levels of total glutathione, IL-8, MMP9, TIMP-1 and MMP9-TIMP-1 complex were highly correlated with each other at Vb, this was inconstant at Vf. Levels of MMP9-TIMP1 complex and of TIMP1 at Vf were significantly lower in workers reporting chlorine puffs with mild acute respiratory symptoms between visits compared to those who had no, or asymptomatic inhalations (P = 0.03 and 0.02, respectively). The fall in FEV1 from Vb to Vf was significantly correlated with levels of glutathione at Vb. Cough between visits was associated with a decrease in FEV1 (P = 0.06). Conclusion:, Although no accelerated loss in FEV1 was documented in these workers exposed to chlorine, subjects with a greater fall in FEV1 were more likely to report cough and have higher levels of total glutathione at Vb. [source]


    Clinical and inflammatory features of occupational asthma caused by persulphate salts in comparison with asthma associated with occupational rhinitis

    ALLERGY, Issue 6 2010
    G. Moscato
    To cite this article: Moscato G, Pala G, Perfetti L, Frascaroli M, Pignatti P. Clinical and inflammatory features of occupational asthma caused by persulphate salts in comparison with asthma associated with occupational rhinitis. Allergy 2010; 65: 784,790. Abstract Background:, The relationships between asthma and rhinitis are still a crucial point in respiratory allergy and have scarcely been analysed in occupational setting. We aimed to compare the clinical and inflammatory features of subjects with occupational asthma only (OA) to subjects with OA associated to occupational rhinitis (OAR) caused by persulphate salts. Methods:, The clinical charts of 26 subjects diagnosed in our Unit as respiratory allergy caused by ammonium persulphate (AP), confirmed by specific inhalation challenge (SIC), were reviewed. Twenty-two out of twenty-six patients underwent pre-SIC-induced sputum challenge test (IS) and 24/26 underwent nasal secretion collection and processing. Results:, Twelve out of twenty-six patients received a diagnosis of OA-only and 14/26 of OAR. Duration of exposure before diagnosis, latency period between the beginning of exposure and asthma symptom onset, basal FEV1, airway reactivity to methacholine and asthma severity did not differ in the two groups. Eosinophilic inflammation of upper and lower airways characterized both groups. Eosinophil percentage in IS tended to be higher in OAR [11.9 (5.575,13.925)%] than in OA-only [2.95 (0.225,12.5)%] (P = 0.31). Eosinophilia in nasal secretions was present both in subjects with OAR [55 (46,71)%] and in subjects with OA-only [38 (15,73.5)%], without any significant difference. Discussion:, Our results indicate that OA because of ammonium persulphate coexists with occupational rhinitis in half of the patients. Unexpectedly, rhinitis did not seem to have an impact on the natural history of asthma. The finding of nasal inflammation in subjects with OA-only without clinical manifestations of rhinitis supports the united airway disease concept in occupational respiratory allergy as a result of persulphates. [source]


    Noninvasive methods for assessment of airway inflammation in occupational settings

    ALLERGY, Issue 4 2010
    S. Quirce
    To cite this article: Quirce S, Lemière C, de Blay F, del Pozo V, Gerth Van Wijk R, Maestrelli P, Pauli G, Pignatti P, Raulf-Heimsoth M, Sastre J, Storaas T, Moscato G. Noninvasive methods for assessment of airway inflammation in occupational settings. Allergy 2010; 65: 445,458. Abstract The present document is a consensus statement reached by a panel of experts on noninvasive methods for assessment of airway inflammation in the investigation of occupational respiratory diseases, such as occupational rhinitis, occupational asthma, and nonasthmatic eosinophilic bronchitis. Both the upper and the lower airway inflammation have been reviewed and appraised reinforcing the concept of ,united airway disease' in the occupational settings. The most widely used noninvasive methods to assess bronchial inflammation are covered: induced sputum, fractional exhaled nitric oxide (FeNO) concentration, and exhaled breath condensate. Nasal inflammation may be assessed by noninvasive approaches such as nasal cytology and nasal lavage, which provide information on different aspects of inflammatory processes (cellular vs mediators). Key messages and suggestions on the use of noninvasive methods for assessment of airway inflammation in the investigation and diagnosis of occupational airway diseases are issued. [source]


    Neutrophilic airway inflammation is a main feature of induced sputum in nonatopic asthmatic children

    ALLERGY, Issue 11 2009
    A. C. Drews
    Background:, Asthma phenotypes are well described among children. However, there are few studies comparing airway inflammation in different clinical presentations of pediatric asthma. We tested the hypothesis that nonatopic asthma is associated with a predominant noneosinophilic inflammation in the airways, as assessed by induced sputum. The objective of this study was to evaluate the cytological characteristics of induced sputum (IS) in atopic (AA), nonatopic asthmatics (NAA) and nonatopic nonasthmatic children (NANA). Methods:, Of 90 selected children, 77 met eligibility criteria for performing IS and were classified as: AA, n = 28, NAA, n = 29 and NANA, n = 19. Subjects answered to a set of ISAAC-based questions and were skin-tested for common aeroallergens. A defined series of exclusion criteria was applied. Results:, Induced sputum was obtained from 54 (70.1%) subjects (21 AA, 20 NAA and 13 NANA). Demographic data and mean FEV1 were similar in the three groups. The proportion of eosinophils [median, inter quartile range (IQR)] was significantly higher in the sputum of AA [(6.0.)12)] compared with NAAs [0 (2)] and NANAs [0 (1)], P < 0.001. The proportion of children with sputum eosinophilia (eos > 3%) was also significantly higher in AA (71.4%) when compared with NAA (28.6%); none of the NANA had sputum eosinophilia. Nonatopic asthmatic children had significantly higher proportions and absolute number of neutrophils than AA and controls. Conclusions:, The results suggest that nonatopic children present IS with a cell pattern that is predominantly neutrophilic while eosinophilia is the hallmark of airway inflammation in the majority of atopic wheezing children not treated with inhaled steroids. [source]


    Relation between inflammation and symptoms in asthma

    ALLERGY, Issue 3 2009
    I. Tillie-Leblond
    Asthma symptoms are the main reason for healthcare utilization and are a fundamental parameter for the evaluation of asthma control. Currently, asthma is defined as a chronic inflammatory disease. A French expert group studied the association between inflammation and asthma symptoms by carrying out a critical review of the international literature. Uncontrolled asthmatics have an increased number of polynuclear eosinophils in the induced sputum and an increased production of exhaled NO. Control by anti-inflammatory treatment is accompanied by a reduction in bronchial eosinophilia and exhaled NO. Asthma symptoms are the result of complex mechanisms and many factors modify their perception. Experimental data suggest that there is a relationship between the perception of symptoms and eosinophilic inflammation and that inhaled corticoid therapy improves this perception. Although they are still not applicable in routine practice, follow-up strategies based on the evaluation of inflammation are thought to be more effective in reducing exacerbations than those usually recommended based on symptoms and sequential analysis of respiratory function. Inhaled corticosteroid therapy is the reference disease-modifying therapy for persistent asthma. Recent studies demonstrated that adjustment of anti-inflammatory treatment based on symptoms is an effective strategy to prevent exacerbations and reduce the total number of doses of inhaled corticosteroids. [source]


    Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment

    ALLERGY, Issue 1 2009
    E. L. J. Van Rensen
    Background:, Anti-IgE, omalizumab, inhibits the allergen response in patients with asthma. This has not been directly related to changes in inflammatory conditions. We hypothesized that anti-IgE exerts its effects by reducing airway inflammation. To that end, the effect of anti-IgE on allergen-induced inflammation in bronchial biopsies in 25 patients with asthma was investigated in a randomized, double-blind, placebo-controlled study. Methods:, Allergen challenge followed by a bronchoscopy at 24 h was performed at baseline and after 12 weeks of treatment with anti-IgE or placebo. Provocative concentration that causes a 20% fall in forced expiratory volume in 1 s (PC20) methacholine and induced sputum was performed at baseline, 8 and 12 weeks of treatment. Changes in the early and late responses to allergen, PC20, inflammatory cells in biopsies and sputum were assessed. Results:, Both the early and late asthmatic responses were suppressed to 15.3% and 4.7% following anti-IgE treatment as compared with placebo (P < 0.002). This was paralleled by a decrease in eosinophil counts in sputum (4,0.5%) and postallergen biopsies (15,2 cells/0.1 mm2) (P < 0.03). Furthermore, biopsy IgE+ cells were significantly reduced between both the groups, whereas high-affinity IgE receptor and CD4+ cells were decreased within the anti-IgE group. There were no significant differences for PC20 methacholine. Conclusion:, The response to inhaled allergen in asthma is diminished by anti-IgE, which in bronchial mucosa is paralleled by a reduction in eosinophils and a decline in IgE-bearing cells postallergen without changing PC20 methacholine. This suggests that the benefits of anti-IgE in asthma may be explained by a decrease in eosinophilic inflammation and IgE-bearing cells. [source]


    Increased prostaglandin E2 levels in the airway of patients with eosinophilic bronchitis

    ALLERGY, Issue 1 2008
    B. Sastre
    Background:, Eosinophilic bronchitis is a common cause of chronic cough, which like asthma is characterized by sputum eosinophilia, but unlike asthma there is no variable airflow obstruction or airway hyperresponsiveness. We tested the hypothesis that the different airway function in patients with eosinophilic bronchitis and asthma could be caused by an imbalance in the production of bronchoconstrictor (LTC4) and bronchoprotective (prostaglandin E2; PGE2) lipid mediators. Methods:, We measured cytokines levels, proinflammatory mediators and eicosanoids concentration in sputum from 13 subjects with nonasthmatic eosinophilic bronchitis, 13 subjects with asthma, and 11 healthy control subjects. Cytokines mRNA levels were measured by real time PCR, proinflammatory mediators, PGE2, and LTC4 were measured by enzyme immunoassays. Results:, The median sputum eosinophil count was not statistically different in patients with asthma (7.95%) and eosinophilic bronchitis (15.29%). The levels of mRNA specific to interleukin-5 (IL-5), IL-4, IL-10, IL-13, interferon , (IFN-,), IL-2, vascular endothelial growth factor and transforming growth factor , were similar in both conditions. In addition, no differences were found between asthma and eosinophilic bronchitis in proinflammatory cytokines, such as IL-8, IFN-, and tumor necrosis factor , (TNF-,) levels. Sputum cysteinyl-leukotrienes concentration was raised both in eosinophilic bronchitis and asthma patients. We found that induced sputum PGE2 concentrations were significantly increased in subjects with eosinophilic bronchitis (838.3 ± 612 pg/ml) when compared with asthmatic (7.54 ± 2.14 pg/ml) and healthy subjects (4 ± 1.3 pg/ml). Conclusion:, This data suggest that the difference in airway function observed in subjects with eosinophilic bronchitis and asthma could be due to differences in PGE2 production in the airways. [source]