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Biomedical subjects

Claus Bachert

Publications and source records attributed to Claus Bachert.

At least 37 records · Page 2Linked to original sources
PubMed2004

Soluble interleukin-5 receptor alpha is increased in acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: During chronic obstructive pulmonary disease (COPD) exacerbations (AE-COPD), an influx of eosinophils into the bronchial mucosa has been described. Eosinophilic cationic protein (ECP) and soluble interleukin-5 receptor alpha (sIL5Ralpha) are secreted by eosinophils and increased in eosinophilic airway diseases. METHODS: We studied ECP and sIL5Ralpha expression in patients with COPD compared to healthy controls and smokers and investigated a possible association to viral exacerbations of COPD. Expression of sIL5Ralpha in serum was analyzed by ELISA and ECP by the Uni-Cap system. Induced sputum from patients with COPD was analyzed for six different respiratory viruses by nested PCR. RESULTS: ECP and sIL5Ralpha were significantly elevated in AE-COPD subjects (n = 54) compared to healthy controls (n = 11, p = 0.018). Furthermore, there was a significant increase in sIL5Ralpha, but not in ECP, in 30 patients with virus-associated AE-COPD compared to smokers without COPD (n = 16) and healthy controls. The increase in FEV(1) after resolution of the AE-COPD correlated with the decrease in sIL5Ralpha (r = 0.269, p = 0.034). CONCLUSIONS: sIL5Ralpha is increased in AE-COPD and not affected by smoking like ECP. sIL5Ralpha is increased in patients with virus-associated AE-COPD compared to smokers and controls. Concentrations of sIL5Ralpha mirror changes in the clinical status and lung function. These data support the involvement of eosinophils in acute exacerbations of COPD.

Blood Proteins↗
PubMed2004

Aspirin sensitivity and IgE antibodies to Staphylococcus aureus enterotoxins in nasal polyposis: studies on the relationship.

BACKGROUND: Nasal polyposis is a multifactorial disease characterized by a chronic eosinophilic inflammation of the sinus mucosa, often associated with asthma and aspirin sensitivity. We have recently shown that the presence of IgE antibodies to Staphylococcus aureus enterotoxins (SAEs) was related to the severity of eosinophilic inflammation in nasal polyp tissue. In this study, we therefore aimed to determine, whether aspirin sensitivity was related to an immune response to SAEs, and how both criteria would be related to eosinophilic inflammation. METHODS: 40 subjects with nasal polyposis (NP) were classified as aspirin-sensitive (n=13, ASNP) or aspirin-tolerant (n=27, ATNP) based on a bronchial aspirin challenge test. Homogenates prepared from nasal polyp tissue and inferior nasal turbinates from healthy subjects (n=12) were analyzed for concentrations of IL-5 by enzyme immunoassay and for ECP, total and IgE to a mix of SAEs (A, C, TSST-1) using the ImmunoCAP system. RESULTS: Concentrations of IL-5, ECP, total IgE, and IgE to an SAE mix were significantly increased in ASNP compared with ATNP patients and controls. In addition, a subgroup analysis showed an increase in eosinophilic markers in ATNP-SAE(+) compared to ATNP-SAE(-). This relationship, however, was not found in ATNP-SAE(+) and ATNP-SAE(-) subjects, indicating that SAE immune response is overlapped or not relevant in this condition. CONCLUSIONS: Aspirin sensitivity was associated with increased concentrations of eosinophil-related mediators, as well as IgE antibodies to SAEs in nasal polyp tissue. However, a direct impact of S. aureus could not be established. It seems that aspirin sensitivity and immune reactions to SAEs are independently related to eosinophilic inflammation.

Adult↗
PubMed2004

Allergic rhinitis: a disease remodeling the upper airways?

The nasal and bronchial mucosa present similarities and differences. Remodeling is defined as "model again or differently, reconstruct" and is present in the airways of most if not all asthmatic patients. Even though inflammation is similar in allergic rhinitis and asthma, the pathologic extent of nasal remodeling in patients with rhinitis seems to be far less extensive than that in the bronchi of asthmatic patients. Epithelial damage is only minimal, and the reticular basement membrane does not appear to be largely pseudothickened. Moreover, the demonstration of fibrogenic growth factors in the nasal mucosa of patients with allergic rhinitis is lacking because of the paucity of studies. The reasons why remodeling appears to be less extensive in the nasal mucosa than in the bronchial mucosa are still unclear, but 2 hypotheses can be put forward. On one hand, the cytokine production of smooth muscle cells might partly explain differences in remodeling of the 2 sites of the airways. On the other hand, the genes of the embryologic differentiation might persist in the nose and bronchi or might be re-expressed in asthma and rhinitis. Because the nose is of ectodermal origin and the bronchi of endodermal origin, these genes might also govern remodeling patterns. More studies are urgently required to better characterize nasal remodeling in patients with rhinitis. A better understanding of nasal and bronchial remodeling might help to identify new pathways and new therapeutic strategies to reduce long-term remodeling in asthma.

Bronchi↗
PubMed2004

Levocetirizine improves quality of life and reduces costs in long-term management of persistent allergic rhinitis.

BACKGROUND: Allergic Rhinitis and its Impact on Asthma in collaboration with the World Health Organization initiative reclassified allergic rhinitis, like asthma, by duration and severity. The Xyzal in Persistent Rhinitis Trial is the first large, long-term clinical trial studying patients with persistent rhinitis as defined by Allergic Rhinitis and its Impact on Asthma. OBJECTIVES: Two primary objectives were defined: comparison of the Rhinoconjunctivitis Quality of Life Questionnaire overall score and Total 5 Symptoms Score (rhinorrhea, sneezing, nasal congestion, and nasal and ocular pruritus) over a period of 4 weeks between levocetirizine 5 mg and placebo. Secondary endpoints included similar evaluations at 1 week and 3, 4.5, and 6 months, summary scores for a general health status questionnaire (Medical Outcomes Survey Short Form 36), a pharmacoeconomic assessment, comorbidities, and a safety evaluation. METHODS: The Xyzal in Persistent Rhinitis Trial was a 6-month double-blind, placebo-controlled, multicenter, multinational trial in 551 patients. Adults with persistent rhinitis sensitized to both grass pollen and house dust mite were randomized to receive levocetirizine 5 mg/d or placebo. RESULTS: A total of 421 patients completed the full study. Levocetirizine significantly improved both the Rhinoconjunctivitis Quality of Life Questionnaire overall score and the Total 5 Symptoms Score from week 1 to 6 months (all P values <.001). Medical Outcomes Survey Short Form 36 summary scores were also improved in the levocetirizine group compared with the placebo group. Treatment cessation because of lack of effect, comorbidities, and overall costs of disease, and comorbidities per working patient per month (160.27 vs 108.18) were lower in the levocetirizine group. CONCLUSION: Levocetirizine was shown to improve quality of life and symptoms and to decrease the overall costs of the disease over the 6-month treatment period.

Adolescent↗
PubMed2004

Increased IgE-antibodies to Staphylococcus aureus enterotoxins in patients with COPD.

Recent evidence suggests that Staphylococcus aureus enterotoxins (SAEs) could modify airway disease by acting as superantigens, an immune response that can be monitored by detection of IgE antibodies to SAEs. We studied the expression of total IgE and specific IgE to SAEs using the Uni-CAP system in healthy controls, smokers without COPD and COPD patients. Only 1/10 controls (10%) and 1/16 smokers (6.3%) had IgE to SAEs compared to 7/18 patients with stable COPD (38.9%) and 21/54 patients with exacerbated COPD (38.9%). The IgE levels to SAEs of the patients with stable COPD (0.18 [0.05-26.2]kUA/l) and the patients with exacerbated COPD (0.09 [0.05-18.6]kUA/l) were significantly higher than those of smokers (n = 16; 0.05 [0.05-0.82]kUA/l) and controls (n = 11; 0.05 [0.05 0.9]kUA/l, P<0.05). IgE to SAEs decreased significantly in the exacerbated patients during hospitalization (0.13 [0.05-18.3] vs. 0.05 [0.05-11]kUA/l, P<0.001) going along with a significant increase in FEV1 (38.1 [16.9-79.5] vs. 51.6 [15-80]%predicted, P<0.001). Similarly to severe asthma, we found significantly elevated IgE to SAE in COPD patients. Our data for the first time suggest differences between healthy subjects, smokers and patients with established COPD regarding the role of bacterial products and point to a possible disease modifying role of SAEs.

Adult↗
PubMed2004

Safety and efficacy of oral fexofenadine in children with seasonal allergic rhinitis--a pooled analysis of three studies.

Allergic rhinitis is one of the most common clinical conditions in children; however, data regarding the safety of antihistamines in children with seasonal allergic rhinitis are limiting. To evaluate the safety and efficacy of fexofenadine in children with seasonal allergic rhinitis, data were pooled from three, double-blind, randomized, placebo-controlled, parallel-group, 2-week trials in children (6-11 year) with seasonal allergic rhinitis. All studies assessed fexofenadine HCl 30 mg b.i.d.; two studies included fexofenadine HCl at 15 and 60 mg b.i.d. Patients (and investigators) reported any adverse events during the trial. Physical examinations, including measurements of vital signs and laboratory tests, were performed. Efficacy assessments (total symptom score and individual symptom scores) were evaluated. Exposure to fexofenadine HCl 30 mg b.i.d. and to any fexofenadine dose exceeded 10,000 and 17,000 patient days, respectively. Incidences of adverse events, and discontinuations because of adverse events, were low and similar across treatment groups. In the placebo group, 24.4% of subjects reported adverse events compared with 24.1% for fexofenadine HCl 30 mg b.i.d., and 28.4% for all fexofenadine-treated groups. The most common adverse event overall was headache (4.3% placebo; 5.8% fexofenadine HCl 30 mg b.i.d.; and 7.2% any fexofenadine doses). Treatment-related adverse events were similar across treatment groups with no sedative effects. Fexofenadine HCl 30 mg b.i.d. was significantly superior to placebo in reducing the total symptom score and all individual seasonal allergic rhinitis symptoms, including nasal congestion (p < 0.05). Fexofenadine, at doses of up to 60 mg b.i.d., is safe and non-sedating, and fexofenadine HCl 30 mg b.i.d. effectively reduces all seasonal allergic rhinitis symptoms in children aged 6-11 years.

Anti-Allergic Agents↗
PubMed2003

Collection of nasal secretions for immunological analysis.

The biochemical analysis of nasal secretions has become essential in the study of nasal or sinus diseases and the monitoring of medical and surgical treatment. The nasal fluid greatly reflects the inflammatory activity within the nasal mucosa. This paper discusses techniques for nasal fluid collection described before and proposes a new approach for the collection and calculation of nasal secretions based on sinus packs. The method is non-invasive, well standardized and reproducible and therefore may serve as a valid tool for future investigations.

Adolescent↗
PubMed2003

Quantitative real time polymerase chain reaction for measurement of human interleukin-5 receptor alpha spliced isoforms mRNA.

BACKGROUND: Expression of human Interleukin-5 receptor alpha (hIL-5Ralpha) is controlled by alternative splicing, which generates two different transcripts encoding a membrane-anchored and a soluble form of the receptor, respectively. Although the study of the expression and regulation of hIL-5Ralpha is of crucial importance in the field of immunological processing, methods and techniques until now described lack sufficient sensitivity for detection of small differences in the expression of these isoforms. The aim of this study was to develop a reliable and sensitive real-time quantitative PCR assay to analyse the expression level of each isoform. METHODS: For the quantitative real-time PCR assay, two standard curves specific for each splice variant were constructed. PCR amplifications were performed on CDNA from peripheral blood, eosinophilic chronic rhinosinusitis and normal nasal tissue using a common forward and two specific reverse primers, in combination with SYBR Green I as the detection format. RESULTS AND CONCLUSION: We have developed an accurate and reliable assay for quantification of interleukin-5 receptor alpha mRNA isoforms over a broad dynamic range of input molecules. Importantly, excess of one isoform did not influence accurate quantification of the other isoform. Quantification of hIL-5Ralpha variants in human samples demonstrated an overexpression of both membrane-anchored and soluble encoding variants in eosinophilic chronic rhinosinusitis tissue and peripheral blood in patients with eosinophilic chronic rhinosinusitis compared to healthy subjects. The implementation of this assay will allow a better understanding of the regulatory mechanisms of the hIL-5Ralpha gene and hence its role in the pathogenesis of chronic inflammatory diseases.

Alternative Splicing↗
PubMed2003

Superantigens and nasal polyps.

Nasal polyps represent an often severe T-cell-orchestrated eosinophilic upper airway disease with currently unknown pathogenesis, often associated with lower airway disease, such as asthma. Superantigens, predominantly derived from Staphylococcus aureus, are potent activators of T cells, induce the synthesis of IgE in B cells, and have direct effects on pro-inflammatory cells, such as eosinophils. IgE antibodies to S. aureus enterotoxins have been described in polyp tissue, linked to a local polyclonal IgE production and an aggravation of eosinophilic inflammation. Furthermore, such IgE antibodies have also been described in the sera of patients with asthma, and linked to severity of disease and steroid insensitivity. This review summarizes our current understanding of the possible role of S. aureus enterotoxins in chronic severe airway disease, such as nasal polyposis.

B-Lymphocytes↗
PubMed2003

Fexofenadine is efficacious and safe in children (aged 6-11 years) with seasonal allergic rhinitis.

BACKGROUND: This is the first prospective, randomized, double-blind, placebo-controlled study showing statistical improvement of an H(1)-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. OBJECTIVE: This randomized, placebo-controlled, parallel-group, double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. METHODS: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (+/-1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point. RESULTS: Fexofenadine was significantly superior to placebo in the primary efficacy analysis (P </=.0001). Individual symptom scores showed statistically significant superiority compared with placebo (P <.05), including nasal congestion in the evening reflective assessment (P <.05). There was no significant difference in adverse events between fexofenadine and placebo, either overall or by causality. CONCLUSION: The efficacy and safety of the H(1)-antihistamine fexofenadine has been confirmed in this multicenter, multinational study of children aged 6 to 11 years with seasonal allergic rhinitis.

Anti-Allergic Agents↗
PubMed2003

Interleukin-5, eosinophilic diseases and therapeutic intervention.

Interleukin 5 (IL-5) is the key cytokine in an eosinophil's life span: it supports eosinophilopoiesis and eosinophil differentiation, contributes to eosinophil migration, tissue localisation and function, and prevents eosinophil apoptosis. Given the likely role of eosinophils in chronic inflammatory diseases, a lot of research over the past decade was aimed at antagonising IL-5 function. It appears from recent studies that, although this can easily be achieved in vitro, blocking IL-5 function in vivo is much more difficult than originally anticipated. Here, we review the current status of IL-5 and IL-5 receptor research, with emphasis on strategies to interfere with IL-5 function.

Animals↗