Biomedical subjects

K M Beeh

Publications and source records attributed to K M Beeh.

25 records · Page 2Linked to original sources

PubMed2000

[Anticholinergic drugs in therapy of chronic obstructive lung disease (COPD)].

Chronic obstructive pulmonary disease (COPD) is a severe respiratory disorder responsible for a significant morbidity and mortality in western societies. In the vast majority of patients, COPD is caused by tobacco smoke. Contributing factors leading to airway obstruction and lung hyperinflation in COPD differ from those observed in asthma, with a major role of hypersecretion and peripheral airway obstruction due to increased cholinergic airway smooth muscle tone. Therefore, anticholinergics are considered the firstline therapy to improve airway obstruction in COPD. In addition to effects on lung function, anticholinergics may also improve exercise tolerance, quality of life and sleep quality in these patients. When compared with other classes of bronchodilators, anticholinergics show an equal potency of bronchodilation, with a favorable safety profile. Due to their unique mechanism of action, anticholinergics can also be combined with different types of bronchodilators. Novel, long-acting anticholinergics may hold a future potential for further improvement of therapy in COPD, particularly in terms of user friendliness and compliance.

Airway Resistance↗

PubMed2000

Elevation of total serum immunoglobulin E is associated with asthma in nonallergic individuals.

Elevated serum immunoglobulin (Ig)E is the hallmark of atopy, and contributes to asthma and bronchial hyperresponsiveness in atopic individuals. In contrast, the significance of IgE in nonallergic subjects is less clear. The aim of the present study is to clarify a potential association of IgE and asthma in absence of clinical allergy. To this purpose 1,219 consecutive patients of a pulmonary practice were evaluated. Nonallergic patients were defined by negative skin prick test, history of atopy and specific IgE, 509 subjects (42%) were nonallergic. Among these, 80 patients (16%) had elevated total IgE levels (>150 U x mL(-1)). Prevalence and severity of asthma in nonallergic subjects with IgE>150 U x mL(-1) were compared with subjects with normal IgE levels, and lung function parameters were correlated with serum IgE in all nonallergic subjects and asthmatics. Asthma was more prevalent in nonallergic subjects with elevated IgE levels than in nonallergic subjects with normal IgE (39% versus 14%; p<0.001). Lung function values of nonallergic asthmatics were lower for forced expiratory volume in one second (FEV1)% predicted (66+20% versus 83+/-17%; p<0.001), FEV1% forced vital capacity (FVC) (70+/-14% versus 81+/-8%; p<0.001) and forced mid expiratory flow (FEF25-75) (1.7+/-0.9 L x s(-1) versus 2.8+/-0.9 L x s(-1); p=0.002) in patients with high IgE compared to asthmatics with normal IgE, and were negatively correlated with log IgE levels in all nonallergic asthmatics. (FEVI % pred: r=-0.5, p<0.001; FEV1% FVC: r=-0.53, p<0.001; FEF25-75: r=-0.52, p<0.001). In the whole study population, multivariate analysis showed a greater than fivefold asthma risk for nonallergic individuals with serum IgE>150 U x mL(-1). These data support the role of IgE as risk factor for asthma independent of allergy, and they further challenge the definition of intrinsic asthma as "non-IgE mediated" entity.

Adult↗

PubMed2000

[efficacy and safety of salmeterol in long-term therapy in patients with chronic obstructive airway diseases].

BACKGROUND: Salmeterol is a long-acting inhaled beta 2-agonist with a bronchodilating effect lasting over 10 to 12 hours. METHODS: A prospective, open, multi-centre study was performed to evaluate the efficacy and safety of inhaled salmeterol (50 micrograms BID) over a mean treatment period of 29 months (range: 4-1145 days) in 634 patients (54% male, age 45 +/- 15 years) with mild to moderate asthma or chronic obstructive pulmonary disease (COPD). Peak expiratory flow rates, rescue use of short acting beta 2-agonists and safety were study objectives. Patients were critically monitored for a possible loss of bronchodilator efficacy of salmeterol during long-term treatment. RESULTS: During the first month of salmeterol therapy, morning peak flow improved from 384 +/- 104 l/min to 413 +/- 112 l/min (p < 0.001), and use of rescue salbutamol was significantly reduced (21 +/- 21 to 8 +/- 14 puffs/week during daytime and 9 +/- 12 to 4.5 +/- 9 puffs/week during nighttime, p < 0.001 both comparisons). Peak flow improvement and reduction of short-acting beta 2-agonist use was maintained during the whole study period. Frequent adverse events were exacerbations of the underlying airway disease (24%) and infections (12%), while typical pharmacological side-effects like tremor or tachycardia where reported in less than 1% of all patients. CONCLUSIONS: These results confirm the persistent efficacy and favourable safety profile of salmeterol during long-term therapy over more than two years. No clinical signs of a decreasing bronchodilator potency indicating tachyphylaxis were observed. Salmeterol treatment provides a therapeutic option to further improve the management and care of patients with moderate obstructive airway diseases.

Administration, Inhalation↗

PubMed2000

[Correlation of plasma glutathione and total IgE level: evidence for a regulatory role of antipxodants in vivo].

BACKGROUND: Atopy is characterized by increased levels of circulating immunoglobulin E (IgE). Moreover, elevated IgE levels are frequently observed in HIV-infected individuals and are of prognostic significance in these patients. Several In vitro studies have established an association of intracellular antioxidants like glutathione with IgE production by B-lymphocytes, suggesting a regulatory role of these substances in IgE synthesis. However, in vivo data consistent with these findings have not been reported. METHODS: Total IgE levels, CD4(+)-lymphocyte count and plasma glutathione were determined in non-atopic, HIV-positive individuals. RESULTS: 27 HIV-positive subjects (mean age Alter +/- SD: 43 +/- 11 years, 85% males) were studied. Mean CD4(+)-lymphocyte count was 250 +/- 136/microliter. The median serum IgE level was 85.3 U/ml (Range: 3-1298 U/ml), and the mean plasma glutathione concentration was 2.08 +/- 0.7 muMol. Plasma glutathione was significantly correlated with CD4(+)-lymphocyte count (r = 0.37; p = 0.05), and was inversely related to total IgE (r = -0.46; p = 0.01). CONCLUSIONS: Plasma glutathione and total IgE levels are negatively correlated in HIV-positive individuals. This observation supports the concept of a regulatory role of antioxidants and IgE synthesis in vivo. Further studies aiming at the possible significance of these mechanisms in atopic patients are clearly warranted.

Adult↗

PubMedDate not supplied

Newly diagnosed chronic obstructive pulmonary disease. Clinical features and distribution of the novel stages of the Global Initiative for Obstructive Lung Disease.

BACKGROUND: The new guidelines of the Global Initiative for Obstructive Lung Disease (GOLD) propose a novel staging system for COPD. This study describes the frequency distribution of GOLD stages in newly diagnosed COPD patients in a large city pulmonary practice. METHODS: All patients newly admitted between 1995 and 1996 were analyzed retrospectively. Incident COPD cases were classified according to GOLD criteria. RESULTS: Among 1,434 patients, 210 were diagnosed with chronic obstructive pulmonary disease (COPD) (60% males, age 55 years, range 20-82 years). 67.5% of the patients were current smokers, 27% ex-smokers, and 5.5% nonsmokers. Based on GOLD criteria, 37% had stage 0, 5% stage I, 46% stage II, and 12% stage III COPD. Symptoms leading patients to seek medical advice were cough (84%), exertional dyspnea (70%), and sputum (45%), with a median symptom duration of 12 months (range 1-240 months). Compared with patients with GOLD stages 0-1, those with stages 2-3 were older (60 vs. 47 years, p < 0.001), heavier smokers (40 vs. 20 pack-years, p < 0.001), had a longer duration of symptoms (24 vs. 6 months, p < 0.001), and elevated IgE (stage 3 only, p < 0.04 vs. stages 0-2). Interestingly, stage 0 COPD patients did not have 'normal' spirometry, as indicated by significantly lower FEV(1) (% predicted) and FEF(25-75) (% predicted), compared with age-matched nonsmoking controls (93.1 +/- 1.8 vs. 99 +/- 1.6, p = 0.004; and 76.2 +/- 2.8 vs. 91.2 +/- 2.9, p = 0.0003, respectively). CONCLUSIONS: The majority of COPD patients seek medical advice at advanced disease stages, and smoke actively despite severe symptoms and functional impairment. However, nearly every second patient presents at stages 0-1, thus opening a window for therapeutic or behavioral intervention. GOLD guidelines are a useful basis to reinforce screening programs aimed at early detection and prevention of progressive COPD in individuals at risk and smoking cessation.

Adult↗

PubMedDate not supplied

Platinum-based, leukocyte-depleting chemotherapy does not alter induced sputum markers of neutrophilic inflammation in COPD patients with unresectable non-small cell lung cancer.

BACKGROUND: Neutrophilic inflammation is a major feature of chronic obstructive pulmonary disease (COPD), and several novel therapies aim at the suppression of neutrophils in COPD. Due to the abundance and redundancy of mediators involved in neutrophilic inflammation, there is an ongoing controversy about the feasibility of such anti-neutrophilic approaches. Systemic chemotherapy has broad side effects, including neutrophil toxicity. OBJECTIVES: In this observational study, we have measured cellular and neutrophil-related inflammatory markers in induced sputum of COPD patients with unresectable non-small cell lung cancer (NSCLC) undergoing platinum-based chemotherapy. METHODS: 15 COPD/NSCLC patients were followed during their first course of chemotherapy with cisplatin (60 mg/m(2) days 1 and 7) and etoposide (100 mg/m(2) days 3, 4, and 5). Sputum induction was performed before, and 3 weeks after chemotherapy. Peripheral blood count, sputum total cells and differentials, and the concentrations of the inflammatory markers interleukin (IL)-8, and matrix metalloproteinase (MMP)-9 in sputum supernatant were analyzed. RESULTS: Similar to COPD controls (n = 12), COPD/NSCLC patients had increased levels of absolute and relative sputum neutrophils, IL-8, and MMP-9 at baseline, when compared with healthy controls (n = 14, p < 0.001, all comparisons). After chemotherapy, there was a significant reduction in peripheral blood leukocytes (pre: 10,736 +/- 550, post: 6,536 +/- 1,064 cells/microl, p = 0.002) and log neutrophils (pre: 8.9 +/- 0.09, post: 8.1 +/- 0.2 cells/microl, p = 0.004), whereas log sputum neutrophils (pre: 0.3 +/- 0.37, post: 0.18 +/- 0.3 cells x 10(6)/ml, p = 0.1), IL-8 (pre 15.9 +/- 3.8, post: 17.7 +/- 3.6 ng/ml, p = 0.7), and log MMP-9 (pre: 5.3 +/- 0.57, post: 5.6 +/- 0.7 ng/ml, p = 0.33) remained unchanged. CONCLUSION: A single course of platinum-based chemotherapy markedly decreases peripheral blood neutrophils, but has no effect on inflammatory patterns of induced sputum in COPD patients with unresectable NSCLC.

Adult↗

PubMedDate not supplied

Stability of glutathione in induced sputum: impact of freezing.

BACKGROUND: Oxidative stress has repeatedly been linked to the pathogenesis of pulmonary disorders like asthma and chronic obstructive pulmonary disease. Measuring glutathione (GSH) in induced sputum (IS) offers a noninvasive tool to study oxidative stress in airway diseases. OBJECTIVES: This study assessed the stability of GSH in sputum supernatant under varying conditions. METHODS: GSH in IS of 14 (7 healthy, 4 chronic obstructive pulmonary disease, 3 allergic rhinitis) nonsmoking subjects was quantified spectrophotometrically. The stability of GSH in supernatant was analyzed over 24 h under different ambient conditions (room temperature and cooling at 4 degrees C). Reproducibility of GSH measurements in immediately processed and frozen supernatant (+72 h) was expressed by intraclass correlation coefficient (R(i)) and coefficient of repeatability (CR). RESULTS: GSH recovery in supernatant decreased in a time- and temperature-dependent manner. Samples stored at 4 degrees C and room temperature showed a rapid decline of stability after 2 h. Mean GSH concentrations in IS after freezing (-20 degrees C) and thawing after 72 h were not significantly different from GSH values measured immediately after processing of the samples (immediate processing: 17.9 +/- 13.9 microM; 72 h freezing: 16.4 +/- 12.9 microM, p = 0.2). The reproducibility between immediately processed and frozen samples was excellent (R(i) = 0.97; CR = 5.7 microM). CONCLUSIONS: Storage of sputum supernatant at room temperature or 4 degrees C leads to a rapid decline of GSH recovery compared with baseline values. Immediate freezing of samples is a suitable and valid alternative to rapid processing and allows collection and shipment of samples for subsequent analysis.

Freezing↗