Sputum

Publication Title: 
Thorax

BACKGROUND: Earlier diagnosis of lung cancer is key to reducing mortality. New evidence suggests that smokers have negative attitudes to screening and participation in lung cancer screening trials is poor (<1 in 6 of those eligible). Understanding participation is important since uptake in screening trials is likely to predict uptake in screening programmes. A qualitative study of people accepting and declining participation in the Lung-SEARCH screening trial was conducted. Two questions were addressed: Are the screening methods offered acceptable to patients?

Author(s): 
Patel, Deesha
Akporobaro, Ajiri
Chinyanganya, Nyasha
Hackshaw, Allan
Seale, Clive
Spiro, Stephen G.
Griffiths, Chris
Lung-SEARCH Investigators
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Chronic neutrophilic inflammation is a manifestation of a variety of lung diseases including cystic fibrosis (CF). There is increasing evidence that fragments of extracellular matrix proteins, such as collagen and elastin, play an important role in inflammatory cell recruitment to the lung in animal models of airway inflammation. Unfortunately, the association of these peptides with human disease and the identification of therapeutic targets directed toward these inflammatory pathways have remained elusive.

Author(s): 
Gaggar, Amit
Jackson, Patricia L.
Noerager, Brett D.
O'Reilly, Philip J.
McQuaid, D. Brent
Rowe, Steven M.
Clancy, J. P.
Blalock, J. Edwin
Publication Title: 
Inhalation Toxicology

Oxidative stress plays a significant role in allergic airway inflammation. Supplementation with alpha-tocopherol (alone or combined with ascorbate/vitamin C) has been assessed as an intervention for allergic airway diseases with conflicting results. Enhancing levels of airway antioxidants with oral supplements has been suggested as an intervention to protect individuals from the effect of inhaled oxidants, although it is unclear whether supplementation changes tocopherol or vitamin C levels in both serum and airway fluids.

Author(s): 
Hernandez, Michelle
Zhou, Haibo
Zhou, Bingqing
Robinette, Carole
Crissman, Kay
Hatch, Gary
Alexis, Neil E.
Peden, David
Publication Title: 
Respiratory Research

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder for which new diagnostic and therapeutic approaches are required. Hallmarks of COPD are matrix destruction and neutrophilic airway inflammation in the lung. We have previously described two tri-peptides, N-alpha-PGP and PGP, which are collagen fragments and neutrophil chemoattractants. In this study, we investigate if N-alpha-PGP and PGP are biomarkers and potential therapeutic targets for COPD.

Author(s): 
O'Reilly, Philip
Jackson, Patricia L.
Noerager, Brett
Parker, Suzanne
Dransfield, Mark
Gaggar, Amit
Blalock, J. Edwin
Publication Title: 
The Journal of Allergy and Clinical Immunology

BACKGROUND: The glutathione-S-transferase Mu 1 (GSTM1) null genotype has been reported to be a risk factor for acute respiratory disease associated with increases in ambient air ozone levels. Ozone is known to cause an immediate decrease in lung function and increased airway inflammation. However, it is not known whether GSTM1 modulates these ozone responses in vivo in human subjects. OBJECTIVE: The purpose of this study was to determine whether the GSTM1 null genotype modulates ozone responses in human subjects.

Author(s): 
Alexis, Neil E.
Zhou, Haibo
Lay, John C.
Harris, Bradford
Hernandez, Michelle L.
Lu, Tsui-Shan
Bromberg, Philip A.
Diaz-Sanchez, David
Devlin, Robert B.
Kleeberger, Steven R.
Peden, David B.
Publication Title: 
Occupational and Environmental Medicine

OBJECTIVE: To determine if the GSTM1 null genotype is a risk factor for increased inflammatory response to inhaled endotoxin. METHODS: 35 volunteers who had undergone inhalation challenge with a 20 000 endotoxin unit dose of Clinical Center Reference Endotoxin (CCRE) were genotyped for the GSTM1 null polymorphism. Parameters of airway and systemic inflammation observed before and after challenge were compared in GSTM1 null (n=17) and GSTM1 (n=18) sufficient volunteers.

Author(s): 
Dillon, Madeline A.
Harris, Bradford
Hernandez, Michelle L.
Zou, Baiming
Reed, William
Bromberg, Philip A.
Devlin, Robert B.
Diaz-Sanchez, David
Kleeberger, Steven
Zhou, Haibo
Lay, John C.
Alexis, Neil E.
Peden, David B.
Publication Title: 
Inhalation Toxicology

CONTEXT: Ozone exposure triggers airway inflammatory responses that may be influenced by biologically active purine metabolites. OBJECTIVE: To examine the relationships between airway purine metabolites and established inflammatory markers of ozone exposure, and to determine if these relationships are altered in individuals with atopy or asthma.

Author(s): 
Esther, Charles R.
Peden, David B.
Alexis, Neil E.
Hernandez, Michelle L.
Publication Title: 
Inhalation Toxicology

BACKGROUND: The evaluation of sputum leukocytes by flow cytometry (FCM) is an opportunity to assess characteristics of cells residing in the central airways, yet it is hampered by certain inherent properties of sputum including mucus and large amounts of contaminating cells and debris. OBJECTIVE: To develop a gating strategy based on specific antibody panels in combination with light scatter properties for flow cytometric evaluation of sputum cells. METHODS: Healthy and mild asthmatic volunteers underwent sputum induction.

Author(s): 
Lay, John C.
Peden, David B.
Alexis, Neil E.
Publication Title: 
Respiratory Research

BACKGROUND: Exposure to ozone activates innate immune function and causes neutrophilic (PMN) airway inflammation that in some individuals is robustly elevated. The interplay between immuno-inflammatory function and genomic signaling in those with heightened inflammatory responsiveness to ozone is not well understood. OBJECTIVES: Determine baseline predictors and post exposure discriminators for the immuno-inflammatory response to ozone in inflammatory responsive adult volunteers.

Author(s): 
Fry, Rebecca C.
Rager, Julia E.
Zhou, Haibo
Zou, Baiming
Brickey, June W.
Ting, Jenny
Lay, John C.
Peden, David B.
Alexis, Neil E.
Publication Title: 
Free Radical Biology & Medicine

Epidemiologic studies suggest that dietary vitamin E is an important candidate intervention for asthma. Our group has shown that daily consumption of vitamin E (γ-tocopherol, γT) has anti-inflammatory actions in both rodent and human phase I studies. The objective of this study was to test whether γT supplementation could mitigate a model of neutrophilic airway inflammation in rats and in healthy human volunteers. F344/N rats were randomized to oral gavage with γT versus placebo, followed by intranasal LPS (20μg) challenge.

Author(s): 
Hernandez, Michelle L.
Wagner, James G.
Kala, Aline
Mills, Katherine
Wells, Heather B.
Alexis, Neil E.
Lay, John C.
Jiang, Qing
Zhang, Hongtao
Zhou, Haibo
Peden, David B.

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