Exhaled markers in the monitoring of airways inflammation and its response to steroid's treatment in mild persistent asthma.

The measure of inflammatory cytokines in the exhaled breath condensate has been recently proposed for use in monitoring asthma and the therapeutic response to steroids. The aim of the present study was to investigate the usefulness of measuring exhaled IL-6, IL-4 and pH in mild persistent asthma. Furthermore the effects on these markers of inhaled steroids were assessed. The study enrolled 28 asthmatic (15 males, 38+/-12 years) and 15 healthy subjects (5 males, 35+/-6 years). IL-6, IL-4 and pH were measured in the exhaled breath condensate of the subjects studied. Significantly higher concentrations of IL-6 and IL-4 were observed in the breath condensate of asthmatic patients (7.1+/-1.1 and 64.4+/-8.3 pg/ml) compared to controls (2.7+/-0.6 and 31.7+/-3.5 pg/ml), p<0.001. Furthermore, exhaled IL-4 fell significantly after treatment with inhaled steroids for 6 months (47.9+/-3.2 pg/ml, p<0.001) while exhaled IL-6 did not (6.4+/-1.0 pg/ml, p=0.8). The exhaled pH turned out to be lower in asthmatic subjects than in controls (7.39+/-0.11 vs. 7.85+/-0.14; P<0.001) but trended towards control levels after steroid treatment (7.65+/-0.16, P<0.001). We conclude that the measurement of exhaled IL-4 and pH in mild asthmatic subjects could be a useful way of monitoring their airway inflammation as well as their response to the treatment.

Exhaled Interleukine-6 and 8-isoprostane in chronic obstructive pulmonary disease: effect of carbocysteine lysine salt monohydrate (SCMC-Lys).

Chronic obstructive pulmonary disease (COPD) is characterized by an airways inflammation and by an enhanced generation of reactive oxygen species. The aim of our study was to assess the inflammation and the oxidative stress in airways of COPD patients with acute exacerbation of disease and in stability. Furthermore, we investigated the anti-inflammatory and antioxidant effects of 6 months treatment with carbocysteine lysine salt monohydrate (SCMC-Lys) in COPD. We studied 30 mild acute COPD, 10 mild stable COPD and 15 healthy subjects. 8-isoprostane and Interleukine-6 were measured in their breath condensate through immunoassay. Significantly higher concentrations of exhaled 8-isoprostane and Interleukine-6 were found in acute COPD patients compared to stable COPD and healthy controls (21.8+/-5.1 vs. 13.2+/-2.0 vs. 4.7+/-1.8 pg/ml and 7.4+/-0.9 vs. 5.8+/-0.2 vs. 2.7+/-0.6 pg/ml, p<0.0001). COPD patients treated with SCMC-Lys showed a marked reduction of exhaled 8-isoprostane and Interleukine-6 (8.9+/-1.5 and 4.6+/-0.8 pg/ml, p<0.0001). These findings suggest that there is an increase of 8-isoprostane and Interleukine-6 concentrations in the breath condensate of COPD patients compared to healthy controls especially during acute exacerbations of the disease. Moreover, we showed an anti-inflammatory and antioxidant effect of short-term administration of SCMC-Lys in COPD, suggesting the importance of a further placebo-controlled study that should evaluate the effects of this drug.

8-Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may compromise oxidative balance. Oxidative stress is increased in the blood and in the airways of OSA patients. DESIGN: The aim of this study was to investigate whether oxidative stress is determined by nocturnal apneas and could be reduced by CPAP therapy, and whether there is a relation between local and systemic oxidative stress in these patients. PATIENTS AND METHODS: Eighteen patients with OSA (13 men; mean [+/- SD] age, 48 +/- 3 years) and 12 healthy age-matched and weight-matched subjects (8 men; mean age, 46 +/- 7 years) were recruited. 8-Isoprostane was measured in exhaled breath condensate and blood by a specific enzyme immunoassay. MEASUREMENTS AND RESULTS: Higher concentrations of 8-isoprostane were found in the morning exhaled condensate (9.5 +/- 1.9 pg/mL) and plasma (9.7 +/- 1.5 pg/mL) of OSA patients compared to healthy obese subjects (6.7 +/- 0.2 and 7.1 +/- 0.3 pg/mL, respectively; p < 0.0001). Elevated mean concentrations of exhaled 8-isoprostane were observed in the OSA patients at 8:00 AM (9.5 +/- 1.9 pg/mL) but not at 8:00 PM (7.6 +/- 0.8 pg/mL; p < 0.0005), and a significant reduction was seen after continuous positive airway pressure (CPAP) therapy (7.7 +/- 0.9 pg/mL; before treatment, 9.6 +/- 1.7 pg/mL; p < 0.005). A positive correlation was found between morning exhaled 8-isoprostane levels and the apnea-hypopnea index (r = 0.8; p < 0.0001), and 8-isoprostane levels and neck circumference (r = 0.6; p < 0.0001). CONCLUSIONS: These findings suggest that systemic and local oxidative stress are increased in OSA patients, and that they are higher after nocturnal apnea and reduced by CPAP therapy.

C-C chemokine receptor 2 and sarcoidosis: association with Lofgren's syndrome.

Sarcoidosis is thought to result from the interaction between an unknown environmental antigenic trigger and the host's genetic susceptibility. We hypothesized that sarcoidosis, or one of the disease subsets, could be associated with single nucleotide polymorphisms of C-C chemokine receptor 2 (CCR2) gene. Eight single-nucleotide polymorphisms in CCR2 were studied in a total of 304 Dutch individuals (90 non-Löfgren sarcoidosis, 47 Löfgren's syndrome, 167 control subjects). From the investigated CCR2 polymorphisms, nine haplotypes were deduced (haplotypes 1-9). In patients with Löfgren's syndrome, a strongly significant increase in the frequency of CCR2-haplotype 2, which includes four unique alleles (A at nucleotide position -6752, A at 3,000, T at 3,547, and T at 4,385), was observed compared with control subjects (74% vs. 38% respectively, p < 0.0001), whereas no difference was found between non-Löfgren sarcoidosis and control subjects (both 38%). The association between CCR2-haplotype 2 carriage frequency and Löfgren's syndrome (odds ratio, 4.4; p < 0.0001) remained significant after adjustment for human leukocyte antigen haplotype DRB1*0301-DQB1*0201 (odds ratio, 11.5; p < 0.0001) and female sex (odds ratio, 3.2; p = 0.003), two known risk factors for Löfgren's syndrome. In conclusion, this report describes a strong association between CCR2-haplotype 2 and Löfgren's syndrome. Further studies are needed to understand the molecular mechanisms underlying this association.

Increased 8-isoprostane and interleukin-6 in breath condensate of obstructive sleep apnea patients.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper airways obstruction during sleep that result in episodes of hypoxia. An increase of systemic biomarkers of inflammation and oxidative stress has been found in patients with OSA and obesity. DESIGN: The aim of this study was to measure the levels of markers of inflammation (interleukin [IL]-6) and oxidative stress (8-isoprostane) in the exhaled breath condensate of OSA and obese patients. PATIENTS AND METHODS: Eighteen OSA patients (13 men; mean [+/- SEM] age, 44 +/- 7 years), 10 obese subjects (4 men; mean age, 39 +/- 8 years), and 15 healthy age-matched subjects (8 men; mean age, 42 +/- 4 years) were recruited. IL-6 and 8-isoprostane were measured in exhaled breath condensate by a specific enzyme immunoassay kit. MEASUREMENTS AND RESULTS: Higher concentrations of IL-6 were found in OSA patients (8.7 +/- 0.3 pg/mL) than in healthy control subjects (1.6 +/- 0.1 pg/mL; p < 0.0001). Obese subjects also had higher levels than healthy control subjects, but lower levels than OSA patients (2.1 +/- 0.2 pg/mL, p < 0.05 and p < 0.0001 respectively). Furthermore, 8-isoprostane levels were found to be higher in OSA patients (7.4 +/- 0.7 pg/mL) than in obese subjects (5 +/- 0.3 pg/mL; p = 0.4) and healthy subjects (4.5 +/- 0.5 pg/mL; p < 0.005). We found a positive correlation between these two markers and neck circumference and apnea/hypopnea index. CONCLUSIONS: These findings suggest that inflammation and oxidative stress are characteristic in the airways of OSA patients but not in obese subjects, and that their levels depend on the severity of the OSA. The measurement of IL-6 and 8-isoprostane levels may prove to be useful in screening and monitoring obese patients who have a high risk of developing OSA.