4-hydroxy-2-nonenal and Asthma

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Asthma; Humans; Ion Channel Gating; Neurons; Pain; Peripheral Nervous System Diseases; Pulmonary Disease, Chronic Obstructive; Transient Receptor Potential Channels

Asthma in obese adults is typically more severe and less responsive to glucocorticoids than asthma in nonobese adults.. We sought to determine whether the clearance of apoptotic inflammatory cells (efferocytosis) by airway macrophages was associated with altered inflammation and reduced glucocorticoid sensitivity in obese asthmatic patients.. We investigated the relationship of efferocytosis by airway (induced sputum) macrophages and blood monocytes to markers of monocyte programming, in vitro glucocorticoid response, and systemic oxidative stress in a cohort of adults with persistent asthma.. Efferocytosis by airway macrophages was assessed in obese (n=14) and nonobese (n=19) asthmatic patients. Efferocytosis by macrophages was 40% lower in obese than nonobese subjects, with a mean efferocytic index of 1.77 (SD, 1.07) versus 3.00 (SD, 1.25; P<.01). A similar reduction of efferocytic function was observed in blood monocytes of obese participants. In these monocytes there was also a relative decrease in expression of markers of alternative (M2) programming associated with efferocytosis, including peroxisome proliferator-activated receptor δ and CX3 chemokine receptor 1. Macrophage efferocytic index was significantly correlated with dexamethasone-induced mitogen-activated protein kinase phosphatase 1 expression (ρ=0.46, P<.02) and baseline glucocorticoid receptor α expression (ρ=0.44, P<.02) in PBMCs. Plasma 4-hydroxynonenal levels were increased in obese asthmatic patients at 0.33 ng/mL (SD, 0.15 ng/mL) versus 0.16 ng/mL (SD, 0.08 ng/mL) in nonobese patients (P=.006) and was inversely correlated with macrophage efferocytic index (ρ=-0.67, P=.02).. Asthma in obese adults is associated with impaired macrophage/monocyte efferocytosis. Impairment of this anti-inflammatory process is associated with altered monocyte/macrophage programming, reduced glucocorticoid responsiveness, and systemic oxidative stress.

Topics: Adult; Aldehydes; Apoptosis; Asthma; Biomarkers; Cohort Studies; Dexamethasone; Dual Specificity Phosphatase 1; Female; Gene Expression; Glucocorticoids; Humans; Inflammation; Macrophages; Male; Middle Aged; Monocytes; Obesity; Oxidative Stress; Phagocytosis; PPAR delta; Receptors, Chemokine; Receptors, Glucocorticoid; Sputum

The main aim of the study was to provide evidence whether professional cleaning was associated with biomarkers of lung damage in non-invasively collected biological fluids (exhaled air and exhaled breath condensate--EBC).. This cross-sectional study involved 40 cleaners regularly exposed to cleaning detergents and 40 controls. The subjects completed a standard questionnaire from European Community Respiratory Health Survey (ECRHS II) and underwent a spirometry. Fractional exhaled nitric oxide (F(E)NO) was measured online, and pH, ammonium (NH(4) (+)), H(2)O(2) and 4-hydroxynonenal (4-HNE) were assayed in EBC.. Among the cleaners, the frequency of asthma and rhinitis was, respectively, 2.5 and 20%. The most frequently reported symptoms were sneezing (27.5%), nasal and/or pharyngeal pruritus (25%), ocular pruritus (22.5%) and cough (22.5%). There were no significant differences in comparison with the control group. Median F(E)NO levels were higher in African than in Caucasian cleaners (21.5 [16.5-30.0] ppb and 18.0 [13.5-20.5] ppb; p < 0.05). H(2)O(2)-EBC (0.26 [0.09-0.53] μM vs. 0.07 [0.04-0.15] μM; p < 0.01), NH(4) (+)-EBC (857 [493-1,305] μM vs. 541 [306-907] μM; p < 0.01) and pH-EBC (8.17 [8.09-8.24] vs. 8.06 [7.81-8.10]; p < 0.01) were higher in the cleaners than in the controls. Finally, the cleaners showed significant correlations between pH-EBC and NH(4) (+)-EBC (r = 0.33, p < 0.05) and a weak correlation between 4-HNE-EBC and H(2)O(2)-EBC (r = 0.37, p < 0.05).. The promising role of EBC analysis in biomonitoring of exposed workers was confirmed. It was also possible to identify the potential biomarkers of exposure to alkaline products (increased ammonium-EBC and pH-EBC levels) and potential biomarkers of oxidative stress (increased H(2)O(2)-EBC levels correlated with 4-HNE-EBC levels) in workers with no signs of airway diseases.

Topics: Aldehydes; Asthma; Biomarkers; Breath Tests; Cross-Sectional Studies; Detergents; Exhalation; Female; Humans; Hydrogen Peroxide; Hydrogen-Ion Concentration; Lung; Male; Nitric Oxide; Occupational Diseases; Occupational Exposure; Pilot Projects; Respiratory Tract Diseases; Rhinitis; Spirometry; Surveys and Questionnaires