1,721,083 research outputs found
Airway inflammation in atopic patients: a comparison of the upper and lower airways
No full textObjective. The purpose of this study was to understand and assess the inflammatory response within the upper and lower airways in patients suffering from both asthma and allergic rhinitis. Study Design. Cross-sectional study. Setting. A laboratory-based study of patients with allergic rhinitis and asthma. Subjects and Methods. Glycol methacrylate resin-embedded specimens from 10 patients with allergic rhinitis and asthma taken from the nose and bronchi were assessed by immunohistochemistry. Monoclonal antibodies directed against specific cell markers for mast cells (AA1), eosinophils (EG2), neutrophils (NOE), and lymphocytes (CD3(+), CD4(+), CD8(+)) were studied. Cells were counted blind (as cells/mm(2)) in the submucosal matrix. Mann-Whitney U test was used for analyses. P values of .05 or lower were considered statistically significant. Results. There was a significant increase in CD4(+) (P = .05) and CD8(+) cell counts (P = .001) in the lower airway compared to the upper airway. There were no differences between the 2 groups in the number of neutrophils, mast cells, eosinophils, and the CD3(+) cell counts. Conclusion. The upper and lower airways have parallel inflammation with possible bidirectional extension of inflammation in patients suffering from asthma and allergic rhinitis. There is increased lymphocytic infiltration in the lower airway, suggesting a possible preponderance for development and maintenance of allergic disease in the lower airway
Analysis of allergen immunotherapy studies shows increased clinical efficacy in highly symptomatic patients
No full textBackground: the assessment of allergen immunotherapy (AIT) efficacy in the treatment for seasonal allergic rhinoconjunctivitis (SAR) symptoms is challenging. Allergen immunotherapy differs from symptomatic therapy in that while symptomatic therapy treats patients after symptoms appear and aims to reduce symptoms, AIT is administered before symptoms are present and aims to prevent them. Thus, clinical studies of AIT can neither establish baseline symptom levels nor limit the enrolment of patients to those with the most severe symptoms. Allergen immunotherapy treatment effects are therefore diluted by patients with low symptoms for a particular pollen season. The objective of this analysis was to assess the effect possible to achieve with AIT in the groups of patients presenting the most severe allergic symptoms.Methods: study centres were grouped into tertiles categorized according to symptom severity scores observed in the placebo patients in each centre (low, middle and high tertiles). The difference observed in the average score in each tertile in active vs placebo-treated patients was assessed. This allowed an estimation of the efficacy that could be achieved in patients from sites where symptoms were high during the pollen season.Results: an increased treatment effect was observed in the most severe patients and was independent of the study analysed and symptom score used.Conclusions: the use of a tertile approach to analyse efficacy in AIT in SAR clinical studies can give a more accurate assessment of potential clinical benefi
Elevation of Candida IgG antibodies in patients with medically unexplained symptoms
No full textBackground: The hypothesis that an immunologic reaction to Candida yeasts, present in the gastrointestinal tract, causes a diffuse collection of multisystem symptoms is not generally accepted within conventional medicine. A questionnaire, the Fungus Related Disease Questionnaire (FRDQ-7), was previously developed and used to identify patients for a randomized, placebo-controlled trial of the nonabsorbed antifungal drug nystatin. Nystatin was superior to placebo in relieving these symptoms. This provides some support for the hypotheses that underpin the "Candida syndrome". Aim: The aim of this study was to identify a population with a high (>9) FRDQ-7 score and symptom-free controls and, subsequently, to explore the relationship between FRDQ-7 scores and Candida immunoglobulin (Ig)A, IgG, and IgM levels. Design: This was a case-controlled study. Methods: Santelmann has suggested that the FRDQ-7 describes people with Candida syndrome if the FRDQ-7 score is >9; 35 patients with medically unexplained symptoms, between ages 18 and 64, were selected for the study if they scored > 9 on the FRDQ-7 questionnaire. Serum Candida IgA, IgG, and IgM measurements were undertaken both for this group and a group of 45 healthy age- and gender-matched controls, and the Ig concentrations were compared. Results: Candida IgG concentration was significantly higher in the noncontrol group than in the control group (p < 0.001). No significant difference was found for Candida IgA or IgM concentrations. Conclusions: Further studies are required to identify whether there is a causal link for the elevation of serum IgG found in this subgroup of patients with increased FRDQ-7 scores, or whether these two observations are parallel manifestations of a common underlying disorder
Expression of c-erbB receptors and ligands in human nasal epithelium
No full textBackground: The epidermal growth factor (EGF) family of growth factors plays an important role in maintenance and repair in a variety of epithelial tissues. However, very little is known about coexpression of these factors and their receptors, the c-erbB family of receptor tyrosine kinases, in human nasal epithelium. Objective: We sought to investigate the expression of these molecules in cultured nasal epithelial cells and nasal mucosa from healthy individuals. Methods: Identification of c-erbB receptors and their ligands was sought by using reverse transcription PCR, Western blotting, and immunohistochemistry. Results: Messenger RNA encoding the EGF receptors (EGFR) c-erbB2 and c-erbB3, but not c-erbB4, was detected in primary cultures of human nasal epithelial cells. Transcripts encoding EGF, heparin-binding EGF, transforming growth factor (TGF) ?, and amphiregulin were also detected. Receptor and ligand expression was confirmed by using immunocytochemical staining of the cells and Western blotting of the cell lysates. Immunohistochemical analysis of tissue sections obtained from biopsy specimens of nasal mucosa revealed intense membrane staining for the EGFR within the respiratory nasal epithelium, which was predominantly localized at the level of the columnar epithelial layers. Similar staining patterns were observed for c-erbB2 and c-erbB3 in the respiratory nasal epithelium. Evidence for EGF, transforming growth factor ?, heparin-binding EGF, amphiregulin, and betacellulin immunostaining in the nasal epithelium was also obtained; their staining patterns paralleled that of EGFR immunostaining. Conclusion: Colocalization of c-erbB receptors and ligands establishes a basis on which to investigate c-erbB receptor– mediated effects in human nasal epithelium
Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids
No full textRationale: patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.Methods: urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study.Measurements and main results : the concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12-18 months.Conclusion: the pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.</p
The relationship between atopic status and IL-10 nasal lavage levels in the acute and persistent inflammatory response to upper respiratory tract infection
No full textWe examined the influence of atopy on virus-induced airway inflammation by comparing the nasal response to naturally acquired upper respiratory tract infection in atopic and nonatopic subjects by measurement of cytokine, chemokine, and mediator levels in nasal lavage from 44 adults (23 atopic) taken during the acute and the convalescent phases of the common cold. Nasal aspirates were examined for the presence of upper respiratory viruses by RT-PCR. In atopic and nonatopic subjects there were increased levels of IL-1, IL-6, IL-8, TNF-, RANTES, sICAM-1, MPO, ECP, IL-10, and IFN- in nasal lavage during the acute compared with the convalescent phase (p < 0.001). During the acute phase histamine levels were significantly higher in the atopic than in the nonatopic subjects (p < 0.05), whereas IL-10 levels were significantly greater in the nonatopic than in the atopic subjects (p < 0.05). At convalescence levels of IL-1, IL-6, sICAM-1, ECP, RANTES and albumin were significantly higher in the atopic group (p < 0.05). An upper respiratory tract virus was found in 27 volunteers (61%) during the acute stage and in two volunteers (4%) at convalescence. We conclude that virus-induced inflammatory changes within the nose are more prolonged in atopic than in nonatopic subjects and that this is associated with reduced IL-10 levels in atopic compared with nonatopic subjects during the acute phase of upper respiratory tract infection. <br/
Salbutamol but not ipratropium abolishes leukotriene D(4)-induced gas exchange abnormalities in asthma
No full textPurpose: leukotriene D(4) (LTD(4)) is a central mediator in asthma inducing bronchoconstriction and profound disturbances in pulmonary gas exchange in asthmatic subjects. The aim of the study was to compare, for the first time, the influence of the bronchodilators salbutamol (400 ?g) and ipratropium (80 ?g) on lung function changes induced by inhaled LTD(4). Methods: treatments were evaluated in a randomized, three-period, double-blind, placebo-controlled, cross-over study where spirometric and pulmonary gas exchange indices were followed in 12 subjects with mild asthma before and after LTD(4) challenge. Results: compared with placebo, salbutamol provided significant protection against the fall in FEV(1) (forced expiratory volume in 1 s) after LTD(4) challenge. Salbutamol also abolished the LTD(4)-induced gas exchange disturbances [decreased arterial oxygen tension (PaO(2)) and increased alveolar-arterial oxygen tension difference (AaPO(2))]. Ipratropium provided significant but less marked attenuation of the changes in FEV(1) and arterial oxygenation induced by LTD(4). Conclusions: despite the equal bronchodilatory effects of salbutamol and ipratropium before the challenge with LTD(4), salbutamol was superior to ipratropium in preventing spirometric and gas exchange abnormalities. This result indicates a broader action of salbutamol on several of the disturbances that contribute to airway obstruction including, for example, exudation of plasma in the airway mucosa. The clinical implication of this new finding is that in this model of acute asthmatic airway obstruction, salbutamol was more effective than ipratropiu
Nasal mucosal immunoexpression of the mast cell chemoattractants TGF-β, eotaxin, and stem cell factor and their receptors in allergic rhinitis
No full textBackgroundAllergic rhinitis is characterized by the epithelial accumulation of cells, particularly mast cells and eosinophils. There is little information relating to the chemotaxins responsible for mast cell epithelial accumulation in this disease.ObjectiveExpression of the mast cell chemoattractants TGF-β, eotaxin, and stem cell factor and their receptors was investigated in tissue sections from biopsy specimens obtained from patients with naturally occurring allergic rhinitis.MethodsSpecific immunohistochemical staining was performed on thin sections of inferior turbinate biopsy specimens from patients with perennial and seasonal allergic rhinitis and, for comparison, from nonatopic and, where relevant, atopic healthy volunteers without rhinitis. Sequential staining of adjacent 2-μm sections was undertaken to colocalize TGF-β receptors to mast cells.ResultsEvidence was found of significantly increased epithelial immunoreactivity for TGF-β1, TGF-β2, TGF-β3, TGF-β receptor I, TGF-β receptor II, and TGF-β receptor III in patients with perennial and seasonal allergic rhinitis compared with that seen in healthy control subjects. TGF-β receptors I and II were found to colocalize to mast cells. Eotaxin epithelial immunoreactivity was significantly increased in the perennial group, although there were no corresponding disease-related differences found in relation to CCR-3 immunoreactivity at this site. There was no increase in stem cell factor immunoreactivity within the epithelium in naturally occurring disease. Significant correlations were found between epithelial immunoreactivity for TGF-β1, TGF-β2, TGF-β receptor I, TGF-β receptor II, and the number of epithelial mast cells.ConclusionThese findings of enhanced epithelial TGF-β immunoreactivity in patients with rhinitis, the correlation with intraepithelial mast cell numbers, and the colocalization of TGF-β receptors to mast cells suggest that the epithelial expression of TGF-β might represent an important biologic process involved in either the recruitment or retention of mast cells within the epithelium in naturally occurring allergic rhinitis
The role of the airway epithelium and its interaction with environmental factors in asthma pathogenesis
No full textAsthma is an inflammatory disorder of the airways dominated by a Th2-type pattern. Because of this, most research has focused on investigating the role of allergic pathways with the hope of discovering novel therapeutic targets. Unfortunately, this strategy (which has been extended to animal models) has failed to identify any therapeutic modalities other than anti-IgE and leukotriene modifiers directed to targets known about for many years. It seems that the problem lies in placing allergy at the center of disease pathogenesis, when in practice other environmental factors may be equally if not more important in the induction and then progression of asthma. An alternative view is that asthma is primarily a defect of epithelial barrier function that, as in atopic dermatitis, allows greater access of environmental allergens, microorganisms, and toxicants to the airway tissue. Evidence is provided to show that both the physical and functional barrier of the airway epithelium is defective in asthma with disrupted tight junctions, reduced antioxidant activity, and impaired innate immunity. This explains the remarkable susceptibility of asthmatic airways to respiratory viruses and the impact of air pollutants on asthma exacerbations. It also provides a mechanism for programming of dendritic cells to drive a Th2 response in the origins of asthma. Viewing asthma primarily as an epithelial disease with adoption of a chronic wound scenario also provides a route to airway wall remodeling and the varying asthma phenotypes over the life course
Evaluation of a rapid lateral flow immunoassay for Staphylococcus aureus detection in respiratory samples
No full textRapid point-of-care pathogen detection remains a challenge in routine diagnostics. A Staphylococcus aureus-specific lateral flow immunochromatography (LFI) test has been developed using a specific monoclonal antibody to the S. aureus cell-wall peptidoglycan. The LFI test was shown to be specific for S. aureus with no signal development for other Staphylococcal species or common respiratory pathogens. Evaluation of S. aureus isolates spiked into induced sputum and bronchoalveolar lavage samples derived from severe asthmatic patients showed a detection limit of 10(6) CFU/mL for the LFI. The test was also shown to successfully detect S. aureus in 1 sample independently determined to be S. aureus positive by quantitative polymerase chain reaction. The ability of the LFI test to rapidly detect S. aureus in clinical respiratory samples suggests that it might be a useful platform for further development of point-of-care diagnostic applications
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