interleukin-8 and Airway-Obstruction

Topics: Airway Obstruction; Asthma; Asthma, Exercise-Induced; Chemotactic Factors; Cold Temperature; Dehydration; Epithelium; Humans; Interleukin-8; Muscle, Smooth; Parasympathetic Nervous System

Neutrophil chemotactic factor (NCF) is a slight acidic macromolecule which is released into the circulation of asthmatic individuals following antigen provocation and an exercise task. It also appears in late asthmatic reactions with a time course of appearance which precedes the second fall in FEV1. The release of NCF was inhibited by prior administration of disodium cromoglycate (DSCG) suggesting its possible mast cell origin.

Topics: Airway Obstruction; Asthma; Asthma, Exercise-Induced; Basophils; Bronchial Provocation Tests; Chemical Phenomena; Chemistry; Chemotactic Factors; Chronic Disease; Forced Expiratory Volume; Histamine Release; Humans; Inflammation; Interleukin-8

Topics: Administration, Intranasal; Airway Obstruction; Animals; Asthma; Bronchial Spasm; Chemotactic Factors; Clinical Trials as Topic; Cromolyn Sodium; Double-Blind Method; Guinea Pigs; Haplorhini; Histamine Release; Humans; Interleukin-8; Long-Term Care; Mast Cells; Sulfur Dioxide; Theophylline

Nocturnal airway obstruction occurs frequently in childhood asthma and results from increased airway inflammation. Lymphocytes are believed to be key effector cells of airway wall inflammation, releasing pro-inflammatory mediators and cytokines. A previous study showed that hydrocortisone infusion, an effective anti-inflammatory treatment, improves nocturnal and daytime FEV(1) values. This study in 16 children with moderate asthma was designed to assess whether there exists day and night differences in IL-4, IL-5, IL-8, and IFN-gamma production of concanavaline A stimulated peripheral blood mononuclear cells. Furthermore, we investigated whether substitution of low serum cortisol levels with intravenous hydrocortisone would affect those parameters. Saline (as a placebo) or hydrocortisone (30 microg/m(2) body surface area/24 h) was intravenously administered in a randomized, double blind, cross-over design. Measurements under saline or hydrocortisone infusions were separated by 1 wk. At 04:00 and 16:00 hours 10 ml blood was taken for determination of peripheral blood mononuclear cell isolation and stimulation, and an eosinophil count. Hydrocortisone infusion significantly reduced the nocturnal fall in FEV(1). Median values of IFNgamma, IL-4, IL-5, and IL-8 produced by peripheral blood mononuclear cells did not significantly differ at 04:00 and 16:00 hours, both with saline and hydrocortisone infusion. Our results suggest that FEV(1) improvement is not due to suppression of circulating peripheral blood mononuclear cell activation. We hypothesize that it is rather due to its effect on local lung tissue epithelial and/or fibroblasts thereby reducing airway inflammation and vascular leakage.

Topics: Adolescent; Airway Obstruction; Anti-Inflammatory Agents; Asthma; Child; Circadian Rhythm; Concanavalin A; Cross-Over Studies; Cytokines; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Infusions, Intravenous; Interferon-gamma; Interleukin-4; Interleukin-5; Interleukin-8; Leukocytes, Mononuclear; Male; Time Factors

To determine the effect of glucocorticoids on grain dust-induced airflow obstruction and airway inflammation.. Randomized controlled trial.. University hospital.. Health volunteers.. Two randomized, placebo-controlled trials, each studying 10 healthy volunteers who were pretreated with either triamcinolone acetonide (Azmacort) oral inhaler 4 puffs twice daily (800 microg daily) for 7 consecutive days or IV hydrocortisone (3 microg/kg/min) as a 14-h continuous infusion, then subjected to a controlled inhalation exposure to corn dust extract (CDE) (endotoxin exposure dose of 3 microg/kg). A single-blind, crossover study design was performed for each trial enrolling 10 healthy, lifetime nonsmokers, with no history of lung disease or environmental exposure to grain dust.. Following each inhalation exposure to CDE, spirometry was performed at regular intervals and BAL was performed at 4 h. Both treatment and placebo groups demonstrated significant decrements in spirometry and increments in BAL cellularity following CDE inhalation compared with placebo. Inhaled steroid treatment resulted in a significantly higher FEV1 only at the 2-h time point following CDE inhalation with no significant differences observed in the BAL total cell concentration or cellular differential compared with placebo. IV hydrocortisone treatment resulted in a significantly higher FEV1 and FVC between 2 and 4 h after CDE inhalation, as well as significant reductions in the BAL total cell, macrophage, and eosinophil concentrations. Interestingly, the concentration of tumor necrosis factor-alpha and interleukin-8 in the BAL fluid was also decreased following treatment with IV glucocorticoids.. These results demonstrate that glucocorticoids, administered IV and perhaps by inhalation, have a mildly protective effect on airflow obstruction and airway inflammation induced by inhalation of grain dust.

Topics: Administration, Inhalation; Adult; Airway Obstruction; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Cell Count; Cross-Over Studies; Dust; Eosinophils; Female; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Humans; Hydrocortisone; Infusions, Intravenous; Interleukin-8; Leukocyte Count; Macrophages, Alveolar; Male; Placebos; Pneumonia; Premedication; Single-Blind Method; Spirometry; Triamcinolone Acetonide; Tumor Necrosis Factor-alpha; Vital Capacity; Zea mays

Pentoxifylline (PTX) has been shown to reduce sepsis-induced neutrophil sequestration in the lung and inhibit endotoxin-mediated release of tumor necrosis factor-alpha (TNF-alpha). Previously, we have shown that endotoxin appears to be the principal agent in grain dust causing airway inflammation and airflow obstruction following grain dust inhalation. To determine whether PTX affects the physiologic and inflammatory events following acute grain dust inhalation, 10 healthy, nonsmoking subjects with normal airway reactivity were treated with PTX or placebo (PL) followed by corn dust extract (CDE) inhalation (0.08 mL/kg), using a single-blinded, crossover design. Subjects received PTX (1,200 mg/d) or PL for 4 days prior to CDE inhalation and 400 mg PTX or PL on the exposure day. Both respiratory symptoms and declines in FEV1 and FVC occurred following CDE exposure in both groups, but there were no significant differences in the frequency of symptoms or percent declines from baseline in the FEV1 and FVC at any of the time points measured in the study. Elevations in peripheral blood leukocyte and neutrophil concentrations and BAL total cell, neutrophil, TNF-alpha, and interleukin-8 concentrations were measured 4 h following exposure to CDE in both the PTX- and PL-treated subjects, but no significant differences were found between treatment groups. These results suggest that pretreatment with PTX prior to inhalation of CDE, in the doses used in this study, does not alter the acute physiologic or inflammatory events following exposure to inhaled CDE.

Topics: Administration, Inhalation; Adult; Airway Obstruction; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cell Movement; Cross-Over Studies; Dust; Edible Grain; Endotoxins; Female; Forced Expiratory Volume; Humans; Interleukin-8; Leukocyte Count; Leukocytes; Lung; Male; Neutrophils; Pentoxifylline; Phosphodiesterase Inhibitors; Placebos; Pneumonia; Single-Blind Method; Tumor Necrosis Factor-alpha; Vital Capacity; Zea mays

Topics: Administration, Intranasal; Airway Obstruction; Animals; Asthma; Bronchial Spasm; Chemotactic Factors; Clinical Trials as Topic; Cromolyn Sodium; Double-Blind Method; Guinea Pigs; Haplorhini; Histamine Release; Humans; Interleukin-8; Long-Term Care; Mast Cells; Sulfur Dioxide; Theophylline

We aim to explore the clinical features and influencing factors of curative effect in children harboring acute laryngitis with laryngeal obstruction.. There involved 237 children with acute laryngitis and 80 healthy children who required physical examination in our hospital between January and September in 2021. The healthy children who required physical examination were allocated into the healthy/control group. The clinical data and laboratory indexes of each group were compared. We also analyzed the risk factors for curative effect of acute laryngitis with laryngeal obstruction among children using univariate/multivariate logistic regression.. The incidence of barking cough, sore throat, dryness, pruritus, dyspnea, diffuse congestion and swelling of laryngeal mucosa and vocal cord congestion or covered with vascular striation in degree III laryngeal obstruction group were significantly higher than other study groups, with degree II laryngeal obstruction group higher than degree I group, and degree I group higher than no laryngeal obstruction group (P<0.05). Moreover, the levels of CRP, TNF-α, IL-6, IL-8 and WBC in degree III laryngeal obstruction group were higher than other three study groups, with degree II higher than degree I laryngeal obstruction group and no obstruction group, and degree I higher than no laryngeal obstruction group (P<0.05). Multivariate logistic regression analysis showed that CRP, TNF-α, IL-6 and IL-8 were the risk factors affecting the curative effect of acute laryngitis with laryngeal obstruction in children, and the differences were statistically significant (P<0.05).. The study revealed the incidence of barking cough, sore throat, dryness, pruritus, dyspnea, diffuse congestion and swelling of laryngeal mucosa vocal cord congestion or covered with vascular striation is highly associated with the severity of acute laryngitis with laryngeal obstruction in children. Additionally, higher levels of CRP, TNF-α, IL-6, IL-8 and WBC indicated serious condition of the disease among children. Hence the risk factors responsible for the efficacy of acute laryngitis in children are CRP, TNF-α, IL-6 and IL-8.

Topics: Airway Obstruction; C-Reactive Protein; Child; Humans; Interleukin-6; Interleukin-8; Laryngeal Diseases; Laryngitis; Tumor Necrosis Factor-alpha

Topics: Airway Obstruction; Asthma; Biomarkers; Bronchial Diseases; Comorbidity; Cross-Sectional Studies; Eosinophilia; Female; Glucocorticoids; Goals; Humans; Interleukin-8; Male; Medication Adherence; Middle Aged; Nebulizers and Vaporizers; Severity of Illness Index; Spain

Secretoglobin family 1A member 1 (SCGB 1A1) is a small protein mainly secreted by mucosal epithelial cells of the lungs and uterus. SCGB 1A1, also known as club (Clara) cell secretory protein, represents a major constituent of airway surface fluid. The protein has anti-inflammatory properties, and its concentration is reduced in equine recurrent airway obstruction (RAO) and human asthma. RAO is characterized by reversible airway obstruction, bronchoconstriction and neutrophilic inflammation. Direct effects of SCGB 1A1 on neutrophil functions are unknown. We have recently identified that the SCGB1A1 gene is triplicated in equids and gives rise to two distinct proteins. In this study we produced the endogenously expressed forms of SCGBs (SCGB 1A1 and 1A1A) as recombinant proteins, and analyzed their effects on reactive oxygen species production, phagocytosis, chemotaxis and neutrophil extracellular trap (NET) formation ex vivo. We further evaluated whether NETs are present in vivo in control and inflamed lungs. Our data show that SCGB 1A1A but not SCGB 1A1 increase neutrophil oxidative burst and phagocytosis; and that both proteins markedly reduce neutrophil chemotaxis. SCGB 1A1A reduced chemotaxis significantly more than SCGB 1A1. NET formation was significantly reduced in a time- and concentration-dependent manner by SCGB 1A1 and 1A1A. SCGB mRNA in bronchial biopsies, and protein concentration in bronchoalveolar lavage fluid, was lower in horses with RAO. NETs were present in bronchoalveolar lavage fluid from horses with exacerbated RAO, but not in fluid from horses with RAO in remission or in challenged healthy horses. These findings indicate that SCGB 1A1 and 1A1A have overlapping and diverging functions. Considering disparities in the relative abundance of SCGB 1A1 and 1A1A in airway secretions of animals with RAO suggests that these functional differences may contribute to the pathogenesis of RAO and other neutrophilic inflammatory lung diseases.

Topics: Airway Obstruction; Animals; Base Sequence; Bronchoalveolar Lavage Fluid; Chemotaxis; Dose-Response Relationship, Drug; Extracellular Traps; Horses; Humans; Interleukin-8; Molecular Sequence Data; Neutrophils; Phagocytosis; Reactive Oxygen Species; Recurrence; Respiratory Burst; RNA, Messenger; Secretoglobins; Time Factors

Heaves, an obstructive neutrophilic airway inflammation of horses, is triggered by dust components such as endotoxin and has similarities to human asthma. Pulmonary intravascular macrophages (PIMs) increase horses' sensitivity to endotoxin-induced lung inflammation; however, their role in an airborne pathology remains unknown. Therefore, we investigated the role of PIMs in the development of heaves in horses. Clinical and inflammatory responses were evaluated following induction of heaves by moldy hay exposure and PIM depletion with gadolinium chloride (GC). Mares (N = 9) were exposed to four treatments: alfalfa cubes (Cb), alfalfa cubes + GC (Cb-GC), moldy hay (MH), and moldy hay + GC (MH-GC). Clinical scores and neutrophil concentrations in bronchoalveolar lavage (BAL) fluid were higher when mares received MH compared with MH-GC. BAL cells from MH-GC-treated mares had significantly lower IL-8 and TLR4 mRNA expression compared with MH-treated mares. In vitro LPS challenge significantly increased IL-8 but not TLR4 mRNA expression in BAL cells recovered from horses fed with MH, but not from the MH-GC treatment. In summary, PIM depletion attenuated clinical scores, reduced the alveolar migration of neutrophils, and decreased the expression of proinflammatory molecules in BAL cells of heaves horses, suggesting a proinflammatory role of PIMs in the development of airborne pathology.

Topics: Airway Obstruction; Animals; Asthma; Blotting, Western; Bronchoalveolar Lavage; Dust; Endotoxins; Female; Horse Diseases; Horses; Humans; Interleukin-8; Lipopolysaccharides; Macrophages, Alveolar; Neutrophils; Pneumonia; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

To test whether chronic bronchial inflammation may be a contributing risk factor for persistent airflow limitation in children born before 32 weeks of gestation in later life.. Thirty-six of 160 children born before 32 completed weeks of gestation who were born between 1988 and 1992 were recruited at a median age of 11 years. Eighteen age-matched children born at term were controls; 47% of the premature infants and 61% of the term born children produced sputum of sufficient quality for interleukin (IL)-8, cell numbers, and differential counts.. Compared with term born children, sputum from the premature group had a higher proportion of neutrophils (62% vs 3.8%; P < .001) and higher IL-8/protein values (1.93 μg/g vs 0.64 μg/g; P = .008). Forced expiratory flow 25%-75% and forced expiratory volume in 1 second/vital capacity were significantly lower (73.4 % vs 116% predicted, P = .002 and 97% vs 101%, P = .012, respectively). Lung function values and sputum indices did not correlate. IL-8/protein and neutrophil percentages correlated significantly with decreasing gestational age (Spearman rank coefficient = -0.58, P = .020 and -.70, P =.03 respectively).. A significant proportion of school children born very preterm demonstrate persistent peripheral airway obstruction that is accompanied by neutrophilic lower airway inflammation.

Topics: Airway Obstruction; Biomarkers; Bronchitis, Chronic; Case-Control Studies; Child; Cross-Sectional Studies; Female; Forced Expiratory Flow Rates; Forced Expiratory Volume; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-8; Logistic Models; Male; Neutrophils; Sputum; Surveys and Questionnaires; Vital Capacity

Topics: Airway Obstruction; Bronchitis, Chronic; Female; Humans; Infant, Premature, Diseases; Interleukin-8; Male; Neutrophils; Sputum

Neuronal nitric oxide synthase is critically involved in the pathogenesis of acute lung injury resulting from combined burn and smoke inhalation injury. We hypothesized that 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, blocks central molecular mechanisms involved in the pathophysiology of this double-hit insult. Twenty-five adult ewes were surgically prepared and randomly allocated to 1) an uninjured, untreated sham group (n = 7), 2) an injured control group with no treatment (n = 7), 3) an injury group treated with 7-nitroindazole from 1-h postinjury to the remainder of the 24-h study period (n = 7), or 4) a sham-operated group subjected only to 7-nitroindazole to judge the effects in health. The combination injury was associated with twofold increased activity of neuronal nitric oxide synthase and oxidative/nitrosative stress, as indicated by significant increases in plasma nitrate/nitrite concentrations, 3-nitrotyrosine (an indicator of peroxynitrite formation), and malondialdehyde lung tissue content. The presence of systemic inflammation was evidenced by twofold, sixfold, and threefold increases in poly(ADP-ribose) polymerase, IL-8, and myeloperoxidase lung tissue concentrations, respectively (each P < 0.05 vs. sham). These molecular changes were linked to tissue damage, airway obstruction, and pulmonary shunting with deteriorated gas exchange. 7-Nitroindazole blocked, or at least attenuated, all these pathological changes. Our findings suggest 1) that nitric oxide formation derived from increased neuronal nitric oxide synthase activity represents a pivotal reactive agent in the patho-physiology of combined burn and smoke inhalation injury and 2) that selective neuronal nitric oxide synthase inhibition represents a goal-directed approach to attenuate the degree of injury.

Topics: Airway Obstruction; Animals; Cell Nucleus; Enzyme Activation; Hemodynamics; Indazoles; Interleukin-8; Lung Injury; Malondialdehyde; Nitrates; Nitric Oxide Synthase Type I; Nitrites; Peroxidase; Poly(ADP-ribose) Polymerases; Pressure; Regional Blood Flow; Respiratory Function Tests; Sheep; Survival Analysis; Trachea; Transcription Factor RelA; Tyrosine

Airway inflammation in recurrent airway obstruction (RAO) is triggered by housing affected horses in stables.It has been suggested that RAO is an allergic condition, but innate immune mechanisms are also involved. Fungal products activate innate immune mechanisms through toll-like receptor 2 (TLR2). In human airway epithelium, TLR2 activation leads to interleukin (IL)-8 production. This pathway is negatively regulated by the zinc finger protein A20. This study was performed to enhance understanding of innate immune mechanisms in RAO.. TLR2 and IL-8 mRNA are elevated in RAO during stabling compared with controls. A20 mRNA is negatively associated with the numbers of airway inflammatory cells.. To determine TLR2, IL-8 and A20 mRNA expression in lungs of stabled and pastured RAO-affected and control horses.. Airway obstruction and inflammatory cell counts in bronchoalveolar lavage were measured, and TLR2, IL-8 and A20 mRNA expression quantified by qRT-PCR in 6 RAO-affected and 6 control horses, during and after exposure to hay and straw.. Airway obstruction and neutrophils were increased in RAO-affected horses during stabling. While stabling increased IL-8, TLR2 and A20 mRNA were unaffected. TLR2 and A20 were significantly correlated (r = 0.83) and A20 mRNA was negatively associated with inflammatory cells.. Stabling does not lead to an increase in TLR2 expression. Other molecules or processes in the TLR2 cascade might be important in fungal-induced airway inflammation. Equine epithelial-derived A20 may be involved in modulation of airway inflammation.

Topics: Airway Obstruction; Animals; Bronchi; Case-Control Studies; Female; Gene Expression Regulation; Horse Diseases; Horses; Housing, Animal; Immunity, Innate; Inflammation; Interleukin-8; Male; Nuclear Proteins; RNA, Messenger; Toll-Like Receptor 2

Previous studies on the relationship of chronic bronchitis to incident airflow limitation and all-cause mortality have provided conflicting results, with positive findings reported mainly by studies that included populations of young adults. This study sought to determine whether having chronic cough and sputum production in the absence of airflow limitation is associated with onset of airflow limitation, all-cause mortality and serum levels of C-reactive protein (CRP) and interleukin-8 (IL-8), and whether subjects' age influences these relationships.. 1412 participants in the long-term Tucson Epidemiological Study of Airway Obstructive Disease who at enrolment (1972-1973) were 21-80 years old and had FEV(1)/FVC (forced expiratory volume in 1 s/forced vital capacity) > or = 70% and no asthma were identified. Chronic bronchitis was defined as cough and phlegm production on most days for > or = 3 months in two or more consecutive years. Incidence of airflow limitation was defined as the first follow-up survey with FEV(1)/FVC <70%. Serum IL-8 and CRP levels were measured in cryopreserved samples from the enrolment survey.. After adjusting for covariates, chronic bronchitis at enrolment significantly increased the risk for incident airflow limitation and all-cause mortality among subjects <50 years old (HR 2.2, 95% CI 1.3 to 3.8; and HR 2.2, 95% CI 1.3 to 3.8; respectively), but not among subjects > or = 50 years old (HR 0.9, 95% CI 0.6 to 1.4; and HR 1.0, 95% CI 0.7 to 1.3). Chronic bronchitis was associated with increased IL-8 and CRP serum levels only among subjects <50 years old.. Among adults <50 years old, chronic bronchitis unaccompanied by airflow limitation may represent an early marker of susceptibility to the effects of cigarette smoking on systemic inflammation and long-term risk for chronic obstructive pulmonary disease and all-cause mortality.

Topics: Adult; Age of Onset; Aged; Aged, 80 and over; Airway Obstruction; Bronchitis, Chronic; C-Reactive Protein; Chronic Disease; Cough; Female; Forced Expiratory Volume; Humans; Interleukin-8; Male; Middle Aged; Risk Factors; Sputum; Vital Capacity; Young Adult

To examine gene expression of selected cytokines in pulmonary mononuclear cells isolated from healthy horses and horses susceptible to recurrent airway obstruction (RAO), and to determine whether interleukin (IL)-17 and IL-23 were associated with pulmonary inflammation.. 6 RAO-susceptible and 5 healthy horses.. Bronchoalveolar lavage cells were retrieved from horses that were stabled and fed dusty hay for 24 hours. Lavage cells devoid of neutrophils were incubated for 24 hours with solutions of PBS, hay dust, lipopolysaccharide, or B-glucan. Gene expression of IL-17, IL-23 (p19 and p40 subunits), IL-8, IL-1B, chemokine (C-X-C motif) ligand 2 (CXCL2), and B-actin was measured by use of real-time reverse transcription PCR assays.. The degree of inherent expression of target genes in bronchoalveolar lavage cells treated with PBSS was not different between the 2 groups of horses. Relative to exposure to PBSS, exposure to the hay dust solution increased gene expression of all cytokines more than 2-fold in cells from both groups of horses, but the magnitudes of these increases were not different between the groups. Exposure to lipopolysaccharide solution increased gene expression of IL-8, CXCL2, and IL-1B in cells from RAO-susceptible horses, but this increase was not significantly different from that in cells from control horses. Exposure to B-glucan solution failed to increase gene expression in cells from either horse group, compared with gene expression when cells were exposed to PBSS.. The acute pulmonary neutrophilia characteristic of RAO was not associated with an increase in upregulation of gene expression of chemokines in pulmonary mononuclear cells from disease-susceptible horses.

Topics: Airway Obstruction; Animals; Chemokines, CXC; Dust; Female; Gene Expression Regulation; Horse Diseases; Horses; Interleukin-17; Interleukin-1beta; Interleukin-23; Interleukin-8; Leukocytes, Mononuclear; Male

The National Institute for Occupational Safety and Health (NIOSH) received a request for evaluation of a water-damaged office building which housed approximately 1300 employees. Workers reported respiratory conditions that they perceived to be building related. We hypothesized that these symptoms were associated with airways inflammation. To test this hypothesis, we assessed airways inflammation in employees using exhaled breath condensate (EBC) and the fraction of exhaled nitric oxide (FENO). In September 2001, a health questionnaire was offered to all employees. Based on this questionnaire, NIOSH invited 356 symptomatic and asymptomatic employees to participate in a medical survey. In June 2002, these employees were offered questionnaire, spirometry, methacholine challenge test, allergen skin prick testing, EBC and FENO. FENO or EBC were completed by 239 participants. As smoking is highly related to the measurements that we used in this study, we included only the 207 current non-smokers in the analyses. EBC interleukin-8 (IL-8) levels, but not nitrite, were significantly higher among workers with respiratory symptoms and in the physician-diagnosed asthmatic group. Of the analyses assessed, EBC IL-8 showed the most significant relationship with a number of symptoms and physician-diagnosed asthma.. Implementation of exhaled breath condensate and exhaled nitric oxide in indoor air quality problems.

Topics: Adult; Air Pollution, Indoor; Airway Obstruction; Exhalation; Female; Fungi; Humans; Interleukin-8; Male; Middle Aged; National Institute for Occupational Safety and Health, U.S.; Nitric Oxide; Occupational Diseases; Occupational Exposure; Respiratory Hypersensitivity; Sick Building Syndrome; Skin Tests; Surveys and Questionnaires; United States; Workplace

Recurrent airway obstruction (RAO) is characterized by neutrophilic airway inflammation and obstruction, and stabling of susceptible horses triggers acute disease exacerbations. Stable dust is rich in endotoxin, which is recognized by Toll-like receptor (TLR) 4. In human bronchial epithelium, TLR4 stimulation leads to elevation of interleukin (IL)-8 mRNA expression. The zinc finger protein A20 negatively regulates this pathway. We hypothesized that TLR4 and IL-8 mRNA and neutrophil numbers are elevated and that A20 mRNA is not increased in RAOs during stabling compared with controls and with RAOs on pasture. We measured the maximal change in pleural pressure (DeltaPpl(max)), determined inflammatory cell counts in bronchoalveolar lavage fluid (BAL), and quantified TLR4, IL-8, and A20 mRNA in bronchial epithelium by quantitative RT-PCR. We studied six horse pairs, each pair consisting of one RAO and one control horse. Each pair was studied when the RAO-affected horse had airway obstruction induced by stabling and after 7, 14, and 28 days on pasture. Stabling increased BAL neutrophils, DeltaPpl(max), and TLR4 (4.14-fold change) significantly in RAOs compared with controls and with RAOs on pasture. TLR4 correlated with IL-8 (R2 = 0.75). Whereas stabling increased IL-8 in all horses, A20 was unaffected. IL-8 was positively correlated with BAL neutrophils (R2 = 0.43) and negatively with A20 (R2 = 0.44) only in RAO-affected horses. Elevated TLR4 expression and lack of A20 upregulation in bronchial epithelial cells from RAO-affected horses may contribute to elevated IL-8 production, leading to exaggerated neutrophilic airway inflammation in response to inhalation of stable dust.

Topics: Airway Obstruction; Animals; Bronchi; Bronchoalveolar Lavage Fluid; Dust; Epithelial Cells; Female; Horse Diseases; Horses; Housing, Animal; Inflammation; Interleukin-8; Male; Respiratory Function Tests; RNA, Messenger; Toll-Like Receptor 4

To evaluate time-dependent alterations in gene expression of chemokines in bronchial epithelium of recurrent airway obstruction (RAO)-affected horses and whether alterations resulted from increases in gene expression of interleukin (IL)-17 in cells isolated from bronchoalveolar lavage fluid (BALF).. 8 RAO-susceptible horses and 9 control horses.. In 2 experiments, both groups of horses were evaluated after being maintained on pasture and after being stabled and fed dusty hay for 1, 14, 35, and 49 days (experiment 1) or 14 and 28 days (experiment 2). In experiment 1, gene expression of IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and Toll-like receptor 4 (TLR4) in epithelium and IL-8, IL-17, and TLR4 in BALF cells was measured. In experiment 2, bronchial biopsy specimens were evaluated for IL-8 immunoreactivity.. In RAO-susceptible horses after 14 days of challenge exposure, there was a 3- and 10-fold increase in gene expression of IL-8 for epithelial and BALF cells and an increase in IL-8 immunoreactivity in epithelial cells. Challenge exposure failed to alter gene expression of CXCL1, GM-CSF, G-CSF, and TLR4 in epithelial cells of any horses at any time point. During challenge exposure, gene expression of BALF cell IL-17 was downregulated in control horses (day 1) and upregulated in RAO-affected horses (day 35).. Epithelial-derived IL-8 may promote airway neutrophilia, but the inciting stimulus is unlikely to be IL-17 because upregulation of this gene is subsequent to that of IL-8 in epithelial cells.

Topics: Airway Obstruction; Animal Feed; Animals; Bronchi; Bronchoalveolar Lavage Fluid; Disease Susceptibility; Gene Expression Regulation; Horse Diseases; Horses; Interleukin-8; Leukocyte Count; Lymphocyte Count; Recurrence; Respiratory Mucosa

To determine whether macrolide antibiotics improve pulmonary function and decrease airway inflammation in cystic fibrosis (CF), we treated 10 patients (females; aged 19-26 years, all colonized with P. aeruginosa, none with atypical Mycobacteria) with 3 weeks of placebo, followed by 6 weeks of clarithromycin (500 mg BID) in a single-blind prospective study. We also determined the safety of sputum induction and the reproducibility of assessing inflammatory markers in induced sputum. Subjects performed spirometry and underwent sputum induction (12-min inhalation of 3% saline) at 3-week intervals. We found that sputum induction was well-tolerated. We also found that the reproducibility was high for neutrophil (PMN) number (R = 0.87, P = 0.009), interleukin (IL)-8 (R = 0.73, P < 0.05, free neutrophil elastase (NE) (R = 0.82, P < 0.05), and myeloperoxidase (MPO) levels (R = 0.86, P < 0.05), but was less so for tumor necrosis factor (TNF)-alpha (R = -0.15, P = 0.7). We found no significant difference in pulmonary function after 6 weeks of treatment with clarithromycin (FEV(1) (% predicted) (mean +/- SEM), 2.2 +/- 0.9 (60 +/- 24%) vs. 2.3 +/- 1 (61 +/- 29%)), and no significant differences in any of the inflammatory indices measured. The median (and range) values before and after treatment for indices of airway inflammation in the induced sputum samples were: for PMNs, 8 (1-326) and 21 (0.2 -175) x 10(6) cells/mL sputum; for IL-8, 156 (24-656) and 202 (16-680) ng/mL; for free NE, 260 (31-1,264) and 237 (49-1,048) microg/mL; for TNF-alpha, 20 (7-128) and 35 (17-87) pg/mL; and for MPO, 169 (13-960) and 195 (14-816) microg/mL. We conclude that clarithromycin is not uniformly effective in improving airway obstruction or in decreasing airway inflammation in patients with CF.

Topics: Adult; Airway Obstruction; Anti-Bacterial Agents; Biomarkers; Clarithromycin; Cystic Fibrosis; Female; Forced Expiratory Volume; Humans; Inflammation; Interleukin-8; Leukocyte Elastase; Male; Neutrophils; Peroxidase; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Respiratory Function Tests; Single-Blind Method; Sputum; Treatment Outcome; Tumor Necrosis Factor-alpha

Grain dust is well known to cause both acute and chronic respiratory disorders, and endotoxins are considered key components in this. Since endotoxins are known to elicit proinflammatory mediators, we investigated cytokine (tumor necrosis factor [TNF], interleukin-6, interleukin-8) release and a number of proinflammatory and anti-inflammatory proteins (soluble TNF receptors, lipopolysaccharide (LPS) binding protein, bactericidal permeability increasing protein (BPI), C-reactive protein) in plasma of workers exposed to grain dust. In two surveys during 1 week, lung function was measured daily before and after the shift, using flow-volume curves and/or forced oscillation measurements. On Monday and Friday, blood samples (30 mL) were drawn and cytokine release was determined by enzyme-linked immunosorbent assay in supernatant of isolated monocytes or whole blood culture, either unstimulated or on the ex vivo stimulation with 3 ng/mL or 1,000 ng/mL endotoxin. Individual exposures were determined from stationary dust measurements at every workplace combined with personal task analysis during all shifts. In both surveys, no cross-week change in lung function parameters was observed. In the first survey (average exposure: 20.2 mg/m3), monocyte spontaneous TNF release was increased sevenfold cross week (p<0.001) and was significantly related both to individual dust exposure (r=0.62) of that week and the increase in soluble TNF receptor 75 kD (r=0.85). In the second survey, where average exposure was much lower (3.67 mg/m3), impedance parameters indicated a significant improvement of airway function, and cross-week changes in inflammatory markers were minimal. Therefore, we conclude that inflammatory events can be used to monitor adverse respiratory effects of moderate grain dust exposure.

Topics: Acute-Phase Proteins; Airway Obstruction; Antimicrobial Cationic Peptides; Biomarkers; Blood Bactericidal Activity; Blood Proteins; C-Reactive Protein; Carrier Proteins; Cytokines; Dust; Edible Grain; Endotoxins; Enzyme-Linked Immunosorbent Assay; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Maximal Expiratory Flow Rate; Maximal Expiratory Flow-Volume Curves; Membrane Glycoproteins; Membrane Proteins; Monocytes; Occupational Exposure; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha