Allergy and Immunology Commons^™

Improving Hpv Vaccination Series Initiation Rates And Compliance Among Indigent Women In South Texas, Ages 19-26, Through Provider Recommendation And Additional Clinic Funding: A Quality Improvement Project, Lacey Cudd

Doctor of Nursing Practice

The purpose of this quality improvement project was to increase human papillomavirus vaccination series initiation rates among indigent women, ages 19-26, at a clinic in South Texas. The human papillomavirus is a sexually transmitted infection that has been associated with multiple types of cancers. Each year, approximately 6.2 million cases of the human papillomavirus infection are diagnosed; as many as 75% of all new infections occur among females 18-26 years of age. The human papillomavirus vaccination has a high efficacy in regards to cancer prevention, preventing as many as 76% of cancers with only one dose. The project included educating …

Characterization Of Murine Breast Cancer Cell Lines For Anti-Cancer Vaccine, Haven N. Frazier

Biological Sciences Undergraduate Honors Theses

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer death among women in the United States (1). While treatments involving radiation and chemotherapy currently exist, disease must be detected early in order for the treatments to be somewhat effective, and there is no effective treatment after metastasis occurs (2). Additionally, current therapies do not mitigate tumor immunosuppression. Decreasing the tumor-associated immunosuppressive conditions while activating antitumor immunity could prevent recurrence and metastasis, possibly leading to an effective treatment for cancer (3). Tumor cell vaccines could possibly address this issue and have become a …

Cigarette Smoke Impairs A2a Adenosine Receptor Mediated Wound Repair Through Up-Regulation Of Duox-1 Expression., Zhi Tian, Hui Zhang, Jendayi Dixon, Nicole Traphagen, Todd A. Wyatt, Kusum K. Kharbanda, Samantha Simet, Narasaiah Kolliputi, Diane S Allen-Gipson

Journal Articles: Pulmonary & Critical Care Med

Cigarette smoke (CS) exposure and intrinsic factors such as the NADPH oxidases produce high levels of reactive oxygen species (ROS), ensuing inflammatory tissue injury. We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H2O2), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H2O2. To test this hypothesis, we used human bronchial epithelial cell line Nuli-1 and C57BL/6 mice. Cells were treated with 5% CS extract (CSE) for various periods of time, and mice were exposed to whole body CS for six weeks. Both CSE and …

Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Organic hog barn dust (HDE) exposure induces lung inflammation and long-term decreases in lung function in agricultural workers. While concentrations of common gasses in confined animal facilities are well characterized, few studies have been done addressing if exposure to elevated barn gasses impacts the lung immune response to organic dusts. Given the well documented effects of hypercapnia at much higher levels we hypothesized that CO2 at 8 h exposure limit levels (5000 ppm) could alter innate immune responses to HDE.

METHODS: Using a mouse model, C57BL/6 mice were nasally instilled with defined barn dust extracts and then housed in …

Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Organic hog barn dust (HDE) exposure induces lung inflammation and long-term decreases in lung function in agricultural workers. While concentrations of common gasses in confined animal facilities are well characterized, few studies have been done addressing if exposure to elevated barn gasses impacts the lung immune response to organic dusts. Given the well documented effects of hypercapnia at much higher levels we hypothesized that CO2 at 8 h exposure limit levels (5000 ppm) could alter innate immune responses to HDE.

METHODS: Using a mouse model, C57BL/6 mice were nasally instilled with defined barn dust extracts and then housed in …

Reduced Microrna-503 Expression Augments Lung Fibroblast Vegf Production In Chronic Obstructive Pulmonary Disease, Jun Ikari, Amy J. Nelson, Jannah Obaid, Alvaro Giron-Martinez, Kumiko Ikari, Fumihiko Makino, Shunichiro Iwasawa, Yoko Gunji, Maha Farid, Xingqi Wang, Hesham Basma, Dawn Demeo, Carol Feghali-Bostwick, Olaf Holz, Klaus Rabe, Xiangde Liu, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Alterations in microRNA (miRNA) expression may contribute to COPD pathogenesis. In COPD, lung fibroblast repair functions are altered in multiple ways, including extracellular mediator release. Our prior study revealed miR-503 expression is decreased in COPD lung fibroblasts, although the exact role played by miR-503 is undetermined. The current study examined a role of miR-503 in cytokine, growth factor and fibronectin production by lung fibroblasts from patients with and without COPD. Primary adult lung fibroblasts were isolated from patients with or without COPD. MiR-503 expression and interleukin (IL)-6, -8, PGE2, HGF, KGF, VEGF and fibronectin release were examined with or without …

Variability In Objective And Subjective Measures Affects Baseline Values In Studies Of Patients With Copd, Wayne H. Anderson, Jae Wook Ha, David J. Couper, Wanda K. O'Neal, R. Graham Barr, Eugene R. Bleecker, Elizabeth E. Carretta, Christopher B. Cooper, Claire M. Doerschuk, M. Bradley Drummond, Meilan K. Han, Nadia N. Hansel, Victor Kim, Eric C. Kleerup, Fernando J. Martinez, Stephen I. Rennard, Donald Tashkin, Prescott G. Woodruff, Robert Paine, Jeffrey L. Curtis, Richard W. Kanner, Spiromics Research Group

Journal Articles: Pulmonary & Critical Care Med

RATIONALE: Understanding the reliability and repeatability of clinical measurements used in the diagnosis, treatment and monitoring of disease progression is of critical importance across all disciplines of clinical practice and in clinical trials to assess therapeutic efficacy and safety.

OBJECTIVES: Our goal is to understand normal variability for assessing true changes in health status and to more accurately utilize this data to differentiate disease characteristics and outcomes.

METHODS: Our study is the first study designed entirely to establish the repeatability of a large number of instruments utilized for the clinical assessment of COPD in the same subjects over the same …

Body Mass Index Change In Gastrointestinal Cancer And Chronic Obstructive Pulmonary Disease Is Associated With Dedicator Of Cytokinesis 1, Merry-Lynn Noelle Mcdonald, Sungho Won, Manuel Mattheisen, Peter J. Castaldi, Michael H. Cho, Erica Rutten, Megan Hardin, Wai-Ki Yip, Stephen I. Rennard, David A. Lomas, Emiel F.M. Wouters, Alvar Agusti, Richard Casaburi, Christoph P. Lange, George O'Connor, Craig P. Hersh, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study.

METHODS: A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years …

Network-Based Analysis Reveals Novel Gene Signatures In Peripheral Blood Of Patients With Chronic Obstructive Pulmonary Disease, Ma'en Obeidat, Yunlong Nie, Virginia Chen, Casey P. Shannon, Anand Kumar Andiappan, Bernett Lee, Olaf Rotzschke, Peter J. Castaldi, Craig P. Hersh, Nick Fishbane, Raymond T. Ng, Bruce Mcmanus, Bruce E. Miller, Stephen I. Rennard, Peter D. Paré, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death and there is a huge unmet clinical need to identify disease biomarkers in peripheral blood. Compared to gene level differential expression approaches to identify gene signatures, network analyses provide a biologically intuitive approach which leverages the co-expression patterns in the transcriptome to identify modules of co-expressed genes.

METHODS: A weighted gene co-expression network analysis (WGCNA) was applied to peripheral blood transcriptome from 238 COPD subjects to discover co-expressed gene modules. We then determined the relationship between these modules and forced expiratory volume in 1 s (FEV …

International Consensus (Icon) On: Clinical Consequences Of Mite Hypersensitivity, A Global Problem., Mario Sánchez-Borges, Enrique Fernandez-Caldas, Wayne R. Thomas, Martin D. Chapman, Bee Wah Lee, Luis Caraballo, Nathalie Acevedo, Fook Tim Chew, Ignacio J. Ansotegui, Leili Behrooz, Wanda Phipatanakul, Roy Gerth Van Wijk, Demoly Pascal, Nelson Rosario, Motohiro Ebisawa, Mario Geller, Santiago Quirce, Susanne Vrtala, Rudolf Valenta, Markus Ollert, Giorgio Walter Canonica, Moises A. Calderón, Charles S. Barnes, Adnan Custovic, Suwat Benjaponpitak, Arnaldo Capriles-Hulett

Manuscripts, Articles, Book Chapters and Other Papers

Since mite allergens are the most relevant inducers of allergic diseases worldwide, resulting in significant morbidity and increased burden on health services, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), the European Academy of Allergy and Clinical Immunology (EAACI), and the World Allergy Organization (WAO), has proposed to issue an International Consensus (ICON) on the clinical consequences of mite hypersensitivity. The objectives of this document are to highlight aspects of mite biology that are clinically relevant, to update the …

Type 2 Immune Responses In The Context Of Helminth Infection, Asthma, Dendritic Cells, And Myeloid Derived Suppressor Cell Function, Sheela Ruby Damle

Theses and Dissertations

Type 2 (T_H2) immune responses evolved to respond to helminth parasite infections by the production of T_H2 cytokines, which stimulate anti-helminth immunity. Macrophage migration inhibitor factor (MIF) is a pleiotropic cytokine, which is produced by many cell types. We demonstrate that mice deficient in MIF have enhanced clearance of a helminth parasite. MIF deficiency in CD4⁺ T cells was found to be the most important for mediating parasite clearance. We mimicked MIF deficiency by administering an inhibitor of the MIF tautomerase activity, sulforaphane, and this also increased parasite clearance (Section I).

T_H2 immune …

Peanut Allergen Threshold Study (Pats): Novel Single-Dose Oral Food Challenge Study To Validate Eliciting Doses In Children With Peanut Allergy, Jonathan O'B. Hourihane, Katrina J. Allen, Wayne G. Shreffler, Gillian Dunngalvin, Julie A. Nordlee, Giovanni A. Zurzolo, Audrey Dunngalvin, Lyle C. Gurrin, Joseph L. Baumert, Steve L. Taylor

Department of Food Science and Technology: Faculty Publications

Background: Eliciting doses (EDs) of allergenic foods can be defined by the distribution of threshold doses for subjects within a specific population. The ED₀₅ is the dose that elicits a reaction in 5% of allergic subjects. The predicted ED₀₅ for peanut is 1.5 mg of peanut protein (6 mg of whole peanut).

Objective: We sought to validate the predicted peanut ED05 (1.5 mg) with a novel single-dose challenge.

Methods: Consecutive eligible children with peanut allergy in 3 centers were prospectively invited to participate, irrespective of previous reaction severity. Predetermined criteria for objective reactions were used …

Erratum To: Scaling Up Strategies Of The Chronic Respiratory Disease Programme Of The European Innovation Partnership On Active And Healthy Ageing (Action Plan B3: Area 5)., J Bousquet, J Farrell, G Crooks, P Hellings, E H. Bel, M Bewick, N H. Chavannes, J Correia De Sousa, A A. Cruz, T Haahtela, G Joos, N Khaltaev, J Malva, A Muraro, M Nogues, S Palkonen, S Pedersen, C Robalo-Cordeiro, B Samolinski, T Strandberg, A Valiulis, A Yorgancioglu, T Zuberbier, A Bedbrook, W Aberer, M Adachi, A Agusti, C A Akdis, M Akdis, J Ankri, A Alonso, I Annesi-Maesano, I J. Ansotegui, J M. Anto, S Arnavielhe, H Arshad, C Bai, I Baiardini, C Bachert, A K. Baigenzhin, C Barbara, E D. Bateman, B Beghé, A Ben Kheder, K S. Bennoor, M Benson, K C. Bergmann, T Bieber, C Bindslev-Jensen, L Bjermer, H Blain, F Blasi, A L. Boner, M Bonini, S Bonini, S Bosnic-Anticevitch, L P. Boulet, R Bourret, P J. Bousquet, F Braido, A H. Briggs, C E. Brightling, J Brozek, R Buhl, P G. Burney, A Bush, F Caballero-Fonseca, D Caimmi, M A. Calderon, P M. Calverley, P A M Camargos, G W. Canonica, T Camuzat, K H. Carlsen, W Carr, A Carriazo, T Casale, A M. Cepeda Sarabia, L Chatzi, Y Z. Chen, R Chiron, E Chkhartishvili, A G. Chuchalin, K F. Chung, G Ciprandi, I Cirule, L Cox, D J. Costa, A Custovic, R Dahl, S E. Dahlen, U Darsow, G De Carlo, F De Blay, T Dedeu, D Deleanu, E De Manuel Keenoy, P Demoly, J A. Denburg, P Devillier, A Didier, A T. Dinh-Xuan, R Djukanovic, D Dokic, H Douagui, G Dray, R Dubakiene, S R. Durham, M S. Dykewicz, Y El-Gamal, R Emuzyte, L M. Fabbri, M Fletcher, A Fiocchi, A Fink Wagner, J Fonseca, W J. Fokkens, F Forastiere, P Frith, M Gaga, A Gamkrelidze, J Garces, J Garcia-Aymerich, B Gemicioğlu, J E. Gereda, S González Diaz, M Gotua, I Grisle, L Grouse, Z Gutter, M A. Guzmán, L G. Heaney, B Hellquist-Dahl, D Henderson, A Hendry, J Heinrich, D Heve, F Horak, J O' B Hourihane, P Howarth, M Humbert, M E. Hyland, M Illario, J C. Ivancevich, J R. Jardim, E J. Jares, C Jeandel, C Jenkins, S L. Johnston, O Jonquet, K Julge, K S. Jung, J Just, I Kaidashev, M R. Khaitov, O Kalayci, A F. Kalyoncu, T Keil, P K. Keith, L Klimek, B Koffi N'Goran, V Kolek, G H. Koppelman, M L. Kowalski, I Kull, P Kuna, V Kvedariene, B Lambrecht, S Lau, D Larenas-Linnemann, D Laune, L T T Le, P Lieberman, B Lipworth, J Li, K Lodrup Carlsen, R Louis, W Macnee, Y Magard, A Magnan, B Mahboub, A Mair, I Majer, M J. Makela, P Manning, S Mara, G D. Marshall, M R. Masjedi, P Matignon, M Maurer, S Mavale-Manuel, E Melén, E Melo-Gomes, E O. Meltzer, A Menzies-Gow, H Merk, J P. Michel, N Miculinic, F Mihaltan, B Milenkovic, G M Y Mohammad, M Molimard, I Momas, A Montilla-Santana, M Morais-Almeida, M Morgan, R Mösges, J Mullol, S Nafti, L Namazova-Baranova, R Naclerio, A Neou, H Neffen, K Nekam, B Niggemann, G Ninot, T D. Nyembue, R E. O'Hehir, K Ohta, Y Okamoto, K Okubo, S Ouedraogo, P Paggiaro, I Pali-Schöll, P Panzner, N Papadopoulos, A Papi, H S. Park, G Passalacqua, I Pavord, R Pawankar, R Pengelly, O Pfaar, R Picard, B Pigearias, I Pin, D Plavec, D Poethig, W Pohl, T A. Popov, F Portejoie, P Potter, D Postma, D Price, K F. Rabe, F Raciborski, F Radier Pontal, S Repka-Ramirez, S Reitamo, S Rennard, F Rodenas, J Roberts, J Roca, L Rodriguez Mañas, C Rolland, M Roman Rodriguez, A Romano, J Rosado-Pinto, N Rosario, L Rosenwasser, M Rottem, D Ryan, M Sanchez-Borges, G K. Scadding, H J. Schunemann, E Serrano, P Schmid-Grendelmeier, H Schulz, A Sheikh, M Shields, N Siafakas, Y Sibille, T Similowski, F E R Simons, J C. Sisul, I Skrindo, H A. Smit, D Solé, T Sooronbaev, O Spranger, R Stelmach, P J. Sterk, J Sunyer, C Thijs, T To, A Todo-Bom, M Triggiani, R Valenta, A L. Valero, E Valia, E Valovirta, E Van Ganse, M Van Hage, O Vandenplas, T Vasankari, B Vellas, J Vestbo, G Vezzani, P Vichyanond, G Viegi, C Vogelmeier, T Vontetsianos, M Wagenmann, B Wallaert, S Walker, D Y. Wang, U Wahn, M Wickman, D M. Williams, S Williams, J Wright, B P. Yawn, P K. Yiallouros, O M. Yusuf, A Zaidi, H J. Zar, M E. Zernotti, L Zhang, N Zhong, M Zidarn, J Mercier

Manuscripts, Articles, Book Chapters and Other Papers

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Interpreting Patient-Reported Outcomes From Clinical Trials In Copd: A Discussion, Paul W. Jones, Stephen I. Rennard, Maggie Tabberer, John H. Riley, Mitra Vahdati-Bolouri, Neil C. Barnes

Journal Articles: Pulmonary & Critical Care Med

One of the challenges faced by the practising physician is the interpretation of patient-reported outcomes (PROs) in clinical trials and the relevance of such data to their patients. This is especially true when caring for patients with progressive diseases such as COPD. In an attempt to incorporate the patient perspective, many clinical trials now include assessments of PROs. These are formalized methods of capturing patient-centered information. Given the importance of PROs in evaluating the potential utility of an intervention for a patient with COPD, it is important that physicians are able to critically interpret (and critique) the results derived from …

Upregulation Of Rgs2: A New Mechanism For Pirfenidone Amelioration Of Pulmonary Fibrosis, Yan Xie, Haihong Jiang, Qian Zhang, Suneet Mehrotra, Peter W. Abel, Myron L. Toews, Dennis W. Wolff, Stephen I. Rennard, Reynold A. Panettieri, Thomas B. Casale, Yaping Tu

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Pirfenidone was recently approved for treatment of idiopathic pulmonary fibrosis. However, the therapeutic dose of pirfenidone is very high, causing side effects that limit its doses and therapeutic effectiveness. Understanding the molecular mechanisms of action of pirfenidone could improve its safety and efficacy. Because activated fibroblasts are critical effector cells associated with the progression of fibrosis, this study investigated the genes that change expression rapidly in response to pirfenidone treatment of pulmonary fibroblasts and explored their contributions to the anti-fibrotic effects of pirfenidone.

METHODS: We used the GeneChip microarray to screen for genes that were rapidly up-regulated upon exposure …

Effects Of Roflumilast In Copd Patients Receiving Inhaled Corticosteroid/Long-Acting Β2-Agonist Fixed-Dose Combination: Re(2)Spond Rationale And Study Design, Stephen I. Rennard, Fernando J. Martinez, Klaus F. Rabe, Sanjay Sethi, Emilio Pizzichini, Andrew Mcivor, Shahid Siddiqui, Antonio Anzueto, Haiyuan Zhu

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Roflumilast, a once-daily, selective phosphodiesterase-4 inhibitor, reduces the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. The RE(2)SPOND study is examining whether roflumilast, when added to an inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fixed-dose combination (FDC), further reduces exacerbations. The methodology is described herein.

METHODS: In this Phase IV, multicenter, double-blind, placebo-controlled, parallel-group trial, participants were randomized 1:1 (stratified by long-acting muscarinic antagonist use) to receive roflumilast or placebo, plus ICS/LABA FDC, for 52 weeks. Eligible participants had severe COPD associated with chronic bronchitis, had two or more moderate-severe exacerbations within …

Copd Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry, Janice M. Leung, Virginia Chen, Zsuzsanna Hollander, Darlene Dai, Scott J. Tebbutt, Shawn D. Aaron, Kathy L. Vandemheen, Stephen I. Rennard, J. Mark Fitzgerald, Prescott G. Woodruff, Stephen C. Lazarus, John E. Connett, Harvey O. Coxson, Bruce Miller, Christoph Borchers, Bruce M. Mcmanus, Raymond T. Ng, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in considerable morbidity and mortality. However, there are no objective biomarkers to diagnose AECOPD.

METHODS: We used multiple reaction monitoring mass spectrometry to quantify 129 distinct proteins in plasma samples from patients with COPD. This analytical approach was first performed in a biomarker cohort of patients hospitalized with AECOPD (Cohort A, n = 72). Proteins differentially expressed between AECOPD and convalescent states were chosen using a false discovery rate < 0.01 and fold change >1.2. Protein selection and classifier building were performed using an elastic net logistic regression model. The performance of the biomarker panel …

Allergic Diseases And Internalizing Behaviors In Early Childhood., Maya K. Nanda, Grace K. Lemasters, Linda Levin, Marc E. Rothenberg, Amal H. Assa'ad, Nicholas Newman, David Bernstein, Gurjit Khurana-Hershey, James E. Lockey, Patrick H. Ryan

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: The relationship between allergic diseases and internalizing disorders has not been well characterized with regard to multiple allergic diseases or longitudinal study. The objective of this study was to examine the association between multiple allergic diseases in early childhood with validated measures of internalizing disorders in the school-age years.

METHODS: Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study underwent skin testing and examinations at ages 1, 2, 3, 4, and 7 years. At age 7, parents completed the Behavior Assessment System for Children, Second Edition (BASC-2), a validated measure of childhood behavior and emotion. …

Effect Of Tiotropium On Night-Time Awakening And Daily Rescue Medication Use In Patients With Copd, Peter M.A. Calverley, Stephen I. Rennard, Emmanuelle Clerisme-Beaty, Norbert Metzdorf, Valentina Bayer Zubek, Richard Zuwallack

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Several small studies found night-time awakenings due to COPD symptoms were associated with decreased health status. In this study, night-time awakenings in patients with COPD were examined and effects of tiotropium therapy evaluated.

METHODS: This study was a post hoc, exploratory, pooled analysis of twin, multicenter, double-blind, randomized, placebo-controlled, parallel-group trials. Patients with stable moderate-to-severe COPD were randomized to tiotropium HandiHaler® (n = 550) or placebo (n = 371) and followed for 13 weeks. During a 2-week, pre-treatment baseline period and for 13 weeks on treatment, self-reported night-time awakenings due to COPD symptoms, rescue medication (albuterol) use, and morning …

Rnai-Mediated Control Of Aflatoxins In Peanut: Method To Analyze Mycotoxin Production And Transgene Expression In The Peanut/Aspergillus Pathosystem, Renee S. Arias, Phat M. Dang, Victor S. Sobolev

United States Department of Agriculture-Agricultural Research Service / University of Nebraska-Lincoln: Faculty Publications

The Food and Agriculture Organization of the United Nations estimates that 25% of the food crops in the world are contaminated with aflatoxins. That represents 100 million tons of food being destroyed or diverted to non-human consumption each year. Aflatoxins are powerful carcinogens normally accumulated by the fungi Aspergillus flavus and A. parasiticus in cereals, nuts, root crops and other agricultural products. Silencing of five aflatoxin-synthesis genes by RNA interference (RNAi) in peanut plants was used to control aflatoxin accumulation following inoculation with A. flavus. Previously, no method existed to analyze the effectiveness of RNAi in individual peanut transgenic events, …

Myd88 In Lung Resident Cells Governs Airway Inflammatory And Pulmonary Function Responses To Organic Dust Treatment., Jill A. Poole, Todd A. Wyatt, Debra J. Romberger, Elizabeth Staab, Samantha Simet, Stephen J. Reynolds, Joseph H. Sisson, Tammy Kielian

Journal Articles: Pulmonary & Critical Care Med

Inhalation of organic dusts within agriculture environments contributes to the development and/or severity of airway diseases, including asthma and chronic bronchitis. MyD88 KO (knockout) mice are nearly completely protected against the inflammatory and bronchoconstriction effects induced by acute organic dust extract (ODE) treatments. However, the contribution of MyD88 in lung epithelial cell responses remains unclear. In the present study, we first addressed whether ODE-induced changes in epithelial cell responses were MyD88-dependent by quantitating ciliary beat frequency and cell migration following wounding by electric cell-substrate impedance sensing. We demonstrate that the normative ciliary beat slowing response to ODE is delayed in …

Cfap54 Is Required For Proper Ciliary Motility And Assembly Of The Central Pair Apparatus In Mice., Casey W. Mckenzie, Branch Craige, Tiffany V. Kroeger, Rozzy Finn, Todd A. Wyatt, Joseph H. Sisson, Jacqueline A. Pavlik, University Of Massachusetts Medical School, Gregory M. Hendricks, George B. Witman, Lance Lee

Journal Articles: Pulmonary & Critical Care Med

Motile cilia and flagella play critical roles in fluid clearance and cell motility, and dysfunction commonly results in the pediatric syndrome primary ciliary dyskinesia (PCD). CFAP221, also known as PCDP1, is required for ciliary and flagellar function in mice and Chlamydomonas reinhardtii, where it localizes to the C1d projection of the central microtubule apparatus and functions in a complex that regulates flagellar motility in a calcium-dependent manner. We demonstrate that the genes encoding the mouse homologues of the other C. reinhardtii C1d complex members are primarily expressed in motile ciliated tissues, suggesting a conserved function in mammalian motile cilia. The …

Exercise Improves Host Response To Influenza Viral Infection In Obese And Non-Obese Mice Through Different Mechanisms., Kristi J. Warren, Molly M. Olson, Nicholas J. Thompson, Mackenzie L. Cahill, Todd A. Wyatt, Kyoungjin J. Yoon, Christina M. Loiacono, Marian L. Kohut

Journal Articles: Pulmonary & Critical Care Med

Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary …

Gait Mechanics In Patients With Chronic Obstructive Pulmonary Disease., Jennifer M. Yentes, Kendra Schmid, Daniel Blanke, Debra J. Romberger, Stephen I. Rennard, Nicholas Stergiou

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by the frequent association of disease outside the lung. The objective of this study was to determine the presence of biomechanical gait abnormalities in COPD patients compared to healthy controls while well rested and without rest.

METHODS: Patients with COPD (N = 17) and aged-matched, healthy controls (N = 21) walked at their self-selected pace down a 10-meter walkway while biomechanical gait variables were collected. A one-minute rest was given between each of the five collected trials to prevent tiredness (REST condition). Patients with COPD then walked at a self-selected pace on …

Identifying Cases Of Undiagnosed, Clinically Significant Copd In Primary Care: Qualitative Insight From Patients In The Target Population, Nancy K. Leidy, Katherine Kim, Elizabeth D. Bacci, Barbara P. Yawn, David M. Mannino, Byron M. Thomashow, R. Graham Barr, Stephen I. Rennard, Julia F. Houfek, Meilan K. Han, Catherine A. Meldrum, Barry J. Make, Russ P. Bowler, Anna W. Steenrod, Lindsey T. Murray, John W. Walsh, Fernando Martinez, High-Risk-Copd Screening Study Group

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations.

AIMS: This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care.

METHODS: Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care). Phase I: Eight focus groups and six telephone interviews were conducted to elicit descriptions of risk factors for COPD, recent or historical acute respiratory events, and symptoms to inform the …

Design Of A Multi-Center Immunophenotyping Analysis Of Peripheral Blood, Sputum And Bronchoalveolar Lavage Fluid In The Subpopulations And Intermediate Outcome Measures In Copd Study (Spiromics), Christine M. Freeman, Sean Crudgington, Valerie R. Stolberg, Jeanette P. Brown, Joanne Sonstein, Neil E. Alexis, Claire M. Doerschuk, Patricia V. Basta, Elizabeth E. Carretta, David J. Couper, Annette T. Hastie, Robert J. Kaner, Wanda K. O'Neal, Robert Paine, Stephen I. Rennard, Daichi Shimbo, Prescott G. Woodruff, Michelle Zeidler, Jeffrey L. Curtis

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) is a multi-center longitudinal, observational study to identify novel phenotypes and biomarkers of chronic obstructive pulmonary disease (COPD). In a subset of 300 subjects enrolled at six clinical centers, we are performing flow cytometric analyses of leukocytes from induced sputum, bronchoalveolar lavage (BAL) and peripheral blood. To minimize several sources of variability, we use a "just-in-time" design that permits immediate staining without pre-fixation of samples, followed by centralized analysis on a single instrument.

METHODS: The Immunophenotyping Core prepares 12-color antibody panels, which are shipped to the six Clinical Centers shortly before …

The Effect Of Statins On Blood Gene Expression In Copd, Ma'en Obeidat, Nick Fishbane, Yunlong Nie, Virginia Chen, Zsuzsanna Hollander, Scottj Tebbutt, Yohan Bossé, Raymond T. Ng, Bruce E. Miller, Bruce Mcmanus, Stephen I. Rennard, Peter D. Paré, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: COPD is currently the fourth leading cause of death worldwide. Statins are lipid lowering agents with documented cardiovascular benefits. Observational studies have shown that statins may have a beneficial role in COPD. The impact of statins on blood gene expression from COPD patients is largely unknown.

OBJECTIVE: Identify blood gene signature associated with statin use in COPD patients, and the pathways underpinning this signature that could explain any potential benefits in COPD.

METHODS: Whole blood gene expression was measured on 168 statin users and 451 non-users from the ECLIPSE study using the Affymetrix Human Gene 1.1 ST microarray chips. …

Identifying A Gene Expression Signature Of Frequent Copd Exacerbations In Peripheral Blood Using Network Methods, Jarrett D. Morrow, Weiliang Qiu, Divya Chhabra, Stephen I. Rennard, Paula Belloni, Anton Belousov, Sreekumar G. Pillai, Craig P. Hersh

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors. Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility. Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations.

METHODS: Gene expression array and plasma biomarker data were obtained using whole-blood samples from subjects enrolled in the Treatment of Emphysema With a Gamma-Selective Retinoid Agonist (TESRA) …

The Omega-3 Fatty Acid Docosahexaenoic Acid Attenuates Organic Dust-Induced Airway Inflammation., Tara M. Nordgren, Taylor D. Friemel, Art J. Heires, Jill A. Poole, Todd A. Wyatt, Debra J. Romberger

Journal Articles: Pulmonary & Critical Care Med

Workers exposed to organic dusts from concentrated animal feeding operations (CAFOs) are at risk for developing airway inflammatory diseases. Available preventative and therapeutic measures for alleviating dust-induced lung disease are inadequate. Because omega-3 fatty acids can mitigate inflammatory processes, we aimed to determine whether nutritional supplementation with the omega-3 fatty acid docosahexaenoic acid (DHA) could reduce the airway inflammatory consequences of exposures to organic dust. Aqueous extracts of organic dusts from swine CAFOs (ODE) were utilized. In DHA-pretreated human bronchial epithelial cells, lung fibroblasts, monocyte cell cultures, and precision-cut murine lung slices, we found that DHA pretreatment dose-dependently decreased ODE-induced …

The Mucosal Expression Pattern Of Interferon-Ε In Rhesus Macaques, Andrew Demers, Guobin Kang, Fangrui Ma, Wuxun Lu, Zhe Yuan, Yue Li, Mark Lewis, Edmundo N. Kraiselburd, Luis Montaner, Qingsheng Li

Qingsheng Li Publications

Type I IFNs play an important role in innate and adaptive immunity against viral infections. A novel type I IFN, namely IFN-ε, which can protect against vaginal transmission of HSV2 and Chlamydia muridarum bacterial infection, has been described in mice and humans. Nevertheless, the principle cell type and the expression pattern of IFN-ε in tissues remain uncertain. In addition, the expression of IFN-ε in Indian rhesus macaques (Macaca mulatta) has not been reported. Here, we analyzed IFN-ε expression in multiple mucosal sites of uninfected or SIV-infected Indian rhesus macaques using IHCS. We report for the first time the …