Reduction of SARS-CoV-2 viral load in exhaled air by antiseptic chewing gum: a pilot trial.

PURPOSE: The dominant route of transmission of SARS-CoV-2 is airborne, through respiratory transmission by aerosols or droplets which can be measured by viral load in exhaled air. Several natural substances have shown antiviral activity. The aim of this pilot study was to investigate the effect of a chewing gum containing natural antiseptic ingredients (cinnamon-, peppermint- and lemon-oil, quercetin, spermidine, ginger and ginseng) on viral load in exhalative air in patients infected with SARS-CoV-2. METHODS: Nine patients infected with SARS-CoV-2 were enrolled and exhaled forcefully into a special mouthpiece at different time points before and after chewing the antiseptic gum. The mouthpiece contained a filter paper serving for extraction of coronaviruses following real-time PCR to quantify the viral load. RESULTS AND CONCLUSION: Cycle threshold (Ct) values of all patients increased after chewing the gum. The mean difference between the Ct values at baseline (before chewing the antiseptic gum) and time point 30 min (15 min after chewing) was 3.8 ± 2.6; (93% viral load reduction; p = 0.002). Time point 15 min (2.7 ± 1.7 (83% viral load reduction; p = 0.003)), 60 min (3.0 ± 3.4 (88% viral load reduction; p = 0.028)), 90 min (3.7 ± 1.8 (92% viral load reduction; p = 0.004)) and 120 min (3.0 ± 3.7 (91% viral load reduction; p = 0.05)) showed similar results. The antiseptic chewing gum demonstrated a significant potential to reduce SARS-CoV-2 viral load in exhalative air and, in this way, reduce further spread and infection risk. Larger placebo-controlled clinical trials are required to confirm these findings further.

Once-daily indacaterol versus twice-daily salmeterol for COPD: a placebo-controlled comparison.

Indacaterol is a novel, inhaled, once-daily, ultra-long-acting ß(2)-agonist bronchodilator recently approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the efficacy and safety of indacaterol compared with placebo and the twice-daily ß(2)-agonist, salmeterol, as an active control. Patients with moderate-to-severe COPD were randomised to 6 months double-blind treatment with indacaterol (150 µg once daily), salmeterol (50 µg twice daily) or placebo. The primary efficacy end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV(1)) after 12 weeks. 1,002 patients were randomised and 838 (84%) completed the study. Indacaterol increased trough FEV(1) at week 12 by 170 mL over placebo (p<0.001) and by 60 mL over salmeterol (p<0.001). Both active treatments improved health status (St George's Respiratory Questionnaire) and dyspnoea (transition dyspnoea index) compared with placebo, with differences between them favouring indacaterol. Safety profiles were similar across the treatment groups, and both indacaterol and salmeterol were well tolerated. Once-daily treatment with 150 µg indacaterol had a significant and clinically relevant bronchodilator effect over 24 h post-dose and improved health status and dyspnoea to a greater extent than twice-daily 50 µg salmeterol. Indacaterol should prove a useful additional treatment for patients with COPD.

Omalizumab in patients with severe persistent allergic asthma in a real-life setting in Germany.

Omalizumab is a humanized monoclonal anti-immunoglobulin E (IgE) antibody indicated in Europe for the treatment of uncontrolled severe persistent allergic (IgE-mediated) asthma despite optimal therapy with inhaled corticosteroids and long-acting beta(2) agonists. Between 2005 and 2007 280 patients (58% female, mean age 44+/-16 yrs., 46% on oral corticosteroids, median serum IgE level 235IU/ml) who met the EU criteria for add-on therapy with anti-IgE were treated prospectively with omalizumab by 134 physicians as part of a post-marketing surveillance trial and were followed-up for 6 months. The median follow-up time was 195 days, the patients were treated with a median dose of 450mg omalizumab every 4 weeks. After 6 months there was a marked effect of omalizumab treatment on daily (-76%) and nocturnal symptoms (-84%), exacerbations (-82%), unscheduled health care contacts (-81%), hospitalizations (-78%) and quality of life (Mini-AQLQ: score increase from 2.9 to 4.5). Overall, efficacy of omalizumab was rated as excellent or good by the majority of physicians (82%) and patients (86%). In 19 patients (7%) omalizumab-related adverse events were recorded. This post-marketing surveillance trial confirms the marked and clinically relevant effect of omalizumab on asthma symptoms and level of asthma control in the majority of patients with severe persistent allergic (IgE-mediated) asthma in a real-life situation.

Effect of the oral leukotriene B4 receptor antagonist LTB019 on inflammatory sputum markers in patients with chronic obstructive pulmonary disease.

This study aimed to evaluate the effect of a LTB4 receptor antagonist on inflammatory markers in induced sputum, in particular sputum neutrophilia, in ex-smokers with moderate stable chronic obstructive pulmonary disease (COPD). The trial followed a double-blind, randomized, cross-over design including two treatment periods (4 weeks) separated by a 4-week washout period. Sputum inductions and lung function measurements were carried out at the beginning of each period, and after 2 and 4 weeks. Twenty-four patients were included (18/6 m/f; mean (+/-S.D.) age 64+/-5 years; FEV 1 57+/-10% predicted); the per-protocol population comprised 17 patients. No significant differences occurred between LTB019 and placebo regarding the percentage of sputum neutrophils (treatment means, 68.0% vs. 69.3%), total cell count (in units of 10(6)/mL, log e of treatment means: 1.56 vs. 1.27), or the levels of MPO, IL-8, and TNF-alpha. There were also no differences in FEV 1, FVC, or the use of rescue medication. We therefore conclude that a 4-week treatment with LTB019 had no effect on sputum neutrophil numbers and related cytokine levels in these patients, despite the plasma concentrations achieved being similar to those shown to prevent the ex vivo LTB4-induced upregulation of CD11b/18 on neutrophils. The present data suggest that LTB4 antagonism by LTB019 is not a promising therapeutic approach for attenuating chronic airway neutrophilia, at least in patients with moderate COPD.

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.

Sputum induction leads to a decrease of exhaled nitric oxide unrelated to airflow.

Measurement of exhaled nitric oxide (eNO) and analysis of induced sputum are both established noninvasive methods for studying airway inflammation in asthma. Both methods are often used sequentially within short time frames. The aim of the present study was to evaluate the influence of sputum induction on eNO in adults and to follow the kinetics of airway eNO production after induction in relation to forced expiratory volume in one second (FEV1). eNO and FEV1 were measured in 41 adult patients (aged 29 (range 23-50) yrs, 56% male) with asymptomatic atopy or mild asthma (mean FEV1 97.2+/-3% predicted) prior to and immediately after sputum induction with hypertonic saline (4%). Sputum induction with isotonic saline was also performed in 13 subjects (control group). Repeatability of eNO decrease after sputum induction was also studied in 27 patients on separate occasions and kinetics of eNO production after sputum induction were followed over 24 h in another 10 patients. Sputum induction with hypertonic, but not isotonic, saline led to a marked decrease in eNO (log) immediately after the procedure (pre: 3.85+/-0.13 parts per billion (ppb); post: 3.24+/-0.14 ppb). This decrease was shown to be highly reproducible and not related to a fall in FEV1 following sputum induction. While FEV1 returned to baseline within 1 h, decreased eNO levels were observed over 4 h and returned to baseline after 24 h. Hypertonic saline sputum induction leads to a prolonged reduction in exhaled nitric oxide in adult atopics that is reproducible within subjects and not related to a reduction in airflow following sputum induction. This methodological interference should be taken into account when sputum induction and exhaled nitric oxide measurements are performed in the same subject.

Sputum matrix metalloproteinase-9, tissue inhibitor of metalloprotinease-1, and their molar ratio in patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and healthy subjects.

BACKGROUND: Matrix-metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), are involved in the turnover of extracellular matrix. Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are inflammatory diseases characterized by excessive matrix degradation and tissue fibrosis. We have compared sputum concentrations of MMP-9, TIMP-1 and the controlling cytokine tumor necrosis factor (TNF)-alpha in patients with COPD, IPF and healthy subjects. METHODS: In a cross-sectional analysis, 12 patients with stable COPD, 15 patients with IPF and 14 healthy subjects underwent sputum induction. Induced sputum cells were counted and concentrations of MMP-9, TIMP-1 and TNF were measured by enzyme immunoassays. RESULTS: Sputum neutrophils were markedly elevated in COPD and IPF patients compared with controls (P<0.001, both comparisons). Concentrations of MMP-9 and the MMP-9:TIMP-1 ratio were increased in COPD (P<0.001 vs. IPF and controls), whereas sputum TIMP-1 levels were both elevated in COPD and IPF (P<0.01 vs. controls, both comparisons). TNF levels were similar in all three groups (P>0.2, all comparisons). MMP-9 concentrations were negatively correlated with airway obstruction (FEV1 FVC) in COPD (rho=-0.62, P=0.03), but not with diffusion capacity or vital capacity (% predicted) in IPF (rho=-0.06, P=0.85, and rho=-0.3, P=0.29, respectively). MMP-9 was positively correlated with sputum neutrophils in all patients (rho=0.68, P<0.0001), and with TNF in COPD patients (rho=0.76, P=0.004). CONCLUSIONS: These data underline the significance of protease/antiprotease imbalance for the pathogenesis of inflammatory lung diseases. Despite similar cellular inflammatory patterns both in COPD and IPF sputa, marked differences were observed with regard to MMP-9:TIMP-1 balance.

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.

A single nasal allergen challenge increases induced sputum inflammatory markers in non-asthmatic subjects with seasonal allergic rhinitis: correlation with plasma interleukin-5.

BACKGROUND: Seasonal allergic rhinitis (SAR) is a risk factor for asthma in affected individuals. Nasal allergic inflammation enhances bone-marrow eosinophil production, mainly via IL-5, and rhinitis patients have increased airway inflammation during the pollen season. OBJECTIVE: To assess the impact of nasal allergy on sputum inflammatory markers. METHODS: In an open-labelled, randomized, placebo-controlled cross-over study with 16 non-asthmatic SAR patients (median age 25 years, 56% males), the effect of a single nasal allergen challenge performed out of season on induced sputum inflammatory parameters was evaluated. SAR patients were identified by history, skin-prick test and specific IgE. All patients had normal lung function/bronchial hyper-responsiveness out of season and a negative asthma/wheezing history. Sputum cells and supernatant levels of ECP, sICAM, IL-5 and IL-10, and plasma levels of IL-5 and ECP, were measured before and 24 h after nasal allergen challenge. After a washout period of at least 4 weeks, the procedure was repeated with placebo challenge (diluent). RESULTS: Nasal allergen challenge led to an increase in sputum ECP (pre = 60 +/- 12, post = 212 +/- 63 micro g/L, P = 0.02 vs. placebo), and sICAM (4.8 +/- 2.7 to 6.5 +/- 2.9 ng/mL, P = 0.02 vs. placebo), whereas IL-10 decreased after provocation (44 +/- 11 to 29 +/- 6 pg/mL, P = 0.06 vs. placebo). Sputum IL-5 was undetectable in all patients. The absolute number of blood and sputum eosinophils did not change significantly after allergen or placebo challenge (P > 0.07, both comparisons). Plasma levels of IL-5 increased after allergen challenge (8.7 +/- 2.9 to 14.5 +/- 3.9 pg/mL, P = 0.001), and the increase in plasma IL-5 was positively correlated with the rise in sputum ECP in a subgroup of 'responders' (n = 12, r = 0.71, P = 0.01). CONCLUSIONS: A single nasal allergen challenge in SAR patients increased markers of allergic inflammation in the lower respiratory tract, possibly via pronounced activation of inflammatory cells through circulating immediate-type reaction cytokines like IL-5. These findings may provide additional explanatory data for the high susceptibility of SAR patients to incident asthma.

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.

Glutathione deficiency of the lower respiratory tract in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown aetiology. Increased oxidant burden and antioxidant, e.g. glutathione (GSH), deficiency in the lower respiratory tract have been thought to play a role in the progression of IPF. Sputum induction is a safe noninvasive tool to study inflammation in the respiratory tract. The aim of the present study was to evaluate the direct measurement of GSH in induced sputum supernatant. Sixteen IPF patients and 15 healthy, nonsmoking subjects underwent sputum induction. Total GSH in sputum, saliva and plasma was measured spectrophotometrically. Sputum GSH was decreased more then four-fold in IPF patients when compared to healthy subjects (mean GSH 1.4+/-0.34 microM versus 5.8+/-0.98 microM). Salivary GSH was generally low or undetectable in all subjects. Plasma GSH levels were lower in IPF patients (0.26+/-0.1 versus 0.74+/-0.16 microM). In IPF patients, there was a borderline correlation of sputum GSH levels with disease duration and lung-function impairment. These data confirm the established role of oxidant/antioxidant imbalance in the pathogenesis of idiopathic pulmonary fibrosis, and show the potential of induced sputum to directly study inflammatory processes and surrogate markers in interstitial lung diseases like idiopathic pulmonary fibrosis.

[Efficacy and safety of salmeterol (50 microgram) and fluticasone (250 microgram) in a single inhaler device (diskus) in patients with mild to moderate asthma]. / Wirksamkeit und Verträglichkeit einer festen Kombination von Salmeterol (50 microgram)/Fluticason (250 microgram) in einem einzigen Inhalationssystem (Diskus) bei Patienten mit leicht- bis mittelgradigem Asthma bronchiale.

BACKGROUND: Inhaled corticosteroids and long-acting beta-agonists are first-line agents for the treatment of patients with persisting bronchial asthma. Several lines of evidence have shown, that inhaled corticosteroids and long-acting beta-agonist have multiple synergisms both in vivo and in vitro, leading to improved clinical asthma control. METHODS: A prospective, open, multi-centre study was performed to evaluate the efficacy and safety of a fixed combination of inhaled Fluticasone (250 microgram BID) and Salmeterol (50 microgram BID) in a single inhaler device (Diskus). 3345 patients (48 % male, mean age 52 years, range 17 - 90 years) with mild to moderate asthma were treated over a period of 8 weeks. Lung function, quality of life and adverse events were evaluated as primary outcome variables. RESULTS: After 8 weeks of treatment, forced expiratory volume in one second (FEV1) improved from 2.37 +/- 0.86 l to 2.7 +/- 0.96 l (p < 0.001). Accordingly, morning peak expiratory flow (PEF) increased from 4.9 +/- 2.1 l/s to 5.6 +/- 2.2 l/s (p < 0.001). Quality of life improved in 90 % of all patients, with an overall increase of 1.1. points. Frequent adverse events included symptoms of asthma (5.3 % of all adverse events) and infections (2.7 %). Typical side-effects of the study medication, e. g. oral candidiasis or tachycardia were observed in less than 2 % of all patients. CONCLUSIONS: These results confirm the efficacy and tolerability of a fixed combination of salmeterol and fluticasone in a single inhaler device (Diskus). Lung function and quality of life were significantly improved in mild to moderate asthmatics. A fixed combination of long-acting beta-agonists and inhaled corticosteroids is therefore considered as a valuable therapeutic option for the treatment of patients with asthma.

Sputum levels of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1, and their ratio correlate with airway obstruction in lung transplant recipients: relation to tumor necrosis factor-alpha and interleukin-10.

BACKGROUND: Chronic transplant rejection is characterized by progressive narrowing of small airways caused by matrix remodeling and fibrosis. Matrix-metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), are involved in the turnover of extracellular matrix. METHODS: To clarify the contribution of MMPs and TIMPs to airway inflammation in patients after lung transplantation (LTx), we used enzyme immunoassays to measure induced sputum concentrations of MMP-9, TIMP-1, and controlling cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 of 30 LTx patients and 15 control subjects. RESULTS: Sputum concentrations of MMP-9, TIMP-1, the MMP-9:TIMP-1 ratio, and TNF-alpha were higher in LTx patients than in control subjects (p < 0.04, all comparisons). The MMP-9, MMP-9:TIMP-1, and TNF-alpha levels were also significantly higher in LTx patients with chronic rejection compared with those with stable organ function (p < 0.03, all comparisons), whereas IL-10 levels were higher in the latter group (p = 0.05). In all LTx patients, MMP-9 and the MMP-9:TIMP-1 ratio were negatively correlated with forced expiratory volume in 1 second values (rho = -0.47, p = 0.01, and rho = -0.53, p = 0.003, respectively). We found that MMP-9 positively correlated with sputum neutrophils and TNF-alpha whereas MMP-9 and TIMP-1 did not correlate with IL-10. CONCLUSIONS: These data underline the possible contribution of proteases such as MMP-9 to chronic transplant rejection, and suggest that an imbalance of MMP-9 and TIMP-1 may be involved in the pathogenesis of airway obstruction after LTx. We found that MMP-mediated inflammation seems to be controlled by TNF-alpha whereas IL-10 might elicit anti-inflammatory effects through different pathways.

Induced sputum cell profiles in lung transplant recipients with or without chronic rejection: correlation with lung function.

BACKGROUND: Sputum induction is a non-invasive procedure for measuring inflammatory processes of the lower respiratory tract. The aim of this study was to establish sputum cell counts and differentials in patients after lung transplantation (LTx), with or without chronic transplant rejection. METHODS: Sputum induction was performed in 41 LTx patients (25 single LTx (sLTx), 16 double LTx (dLTx) and 15 healthy non-smoking volunteers. Sputum was processed according to standard protocols. Total cell count was calculated as mean (SE) cells x 10(6)/ml sputum and cell differential (%) was evaluated after staining. Cellular profiles were correlated with lung function. RESULTS: Total sputum cell counts were increased in sLTx (9 (1.9) cells x 10(6)/ml, p=0.01) and dLTx patients (7.2 (1.5) x 10(6)/ml, p=0.01) compared with healthy controls (2.6 (0.6) x 10(6)/ml). There was also a marked sputum neutrophilia in both patient groups (59 (6)% and 62 (6)%, respectively, p<0.001 v controls). Moreover, in both sLTx and dLTx patients with chronic transplant rejection there was an increased number of sputum neutrophils compared with patients with normal graft function (p<0.05 both comparisons), and neutrophils were inversely correlated with lung function (forced expiratory volume in one second (FEV(1)) % predicted): sLTx, r=-0.61, p=0.001; dLTx, r=-0.75, p=0.001, respectively). Sputum lymphocytes and eosinophils were similar in both groups. No relevant side effects occurred during sputum induction. CONCLUSIONS: Sputum induction is a safe and non-invasive tool for monitoring lower respiratory tract inflammation in LTx patients. Both sLTx and dLTx patients with chronic rejection had increased sputum neutrophils compared with patients with normal transplant function. These data support findings of other authors highlighting a possible role for neutrophils in the pathogenesis of chronic transplant rejection.

[Correlation of plasma glutathione and total IgE level: evidence for a regulatory role of antipxodants in vivo]. / Korrelation von Plasma-Glutathion und Gesamt-IgE-Spiegeln: Hinweise für eine regulatorische Rolle von Antioxidantien 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.