Respiratory Tract Diseases Commons^™

A Highly Stable Prefusion Rsv F Vaccine Derived From Structural Analysis Of The Fusion Mechanism, Anders Krarup, Daphné Truan, Polina Furmanova-Hollenstein, Lies Bogaert, Pascale Bouchier, Ilona Bisschop, Myra Widjojoatmodjo, Roland Zahn, Hanneke Schuitemaker, Jason Mclellan, Johannes Langedijk

Dartmouth Scholarship

Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections and is the leading cause of infant hospitalizations. Recently, a promising vaccine antigen based on the RSV fusion protein (RSV F) stabilized in the native prefusion conformation has been described. Here we report alternative strategies to arrest RSV F in the prefusion conformation based on the prevention of hinge movements in the first refolding region and the elimination of proteolytic exposure of the fusion peptide. A limited number of unique mutations are identified that stabilize the prefusion conformation of RSV F and dramatically increase expression levels. This highly stable prefusion …

Amikacin Concentrations Predictive Of Ototoxicity In Multidrug-Resistant Tuberculosis Patients, Chawangwa Modongo, Jotam G. Pasipanodya, Nicola M. Zetola, Scott M. Williams

Dartmouth Scholarship

Aminoglycosides, such as amikacin, are used to treat multidrug-resistant tuberculosis. However, ototoxicity is a common problem and is monitored using peak and trough amikacin concentrations based on World Health Organization recommendations. Our objective was to identify clinical factors predictive of ototoxicity using an agnostic machine learning method. We used classification and regression tree (CART) analyses to identify clinical factors, including amikacin concentration t

hresholds that pre- dicted audiometry-confirmed ototoxicity among 28 multidrug-resistant pulmonary tuberculosis patients in Botswana. Amika- cin concentrations were measured for all patients. The quantitative relationship between predictive factors and the probability of ototoxicity were then identified using …

New Evidence Prompts Rethinking The Clinical Management Of Community Acquired Pneumonia In Patients Admitted To General Medical Services., J. Timothy Caldwell

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Postma DF, van Werkhoven CH, van Elden LJR, et al. Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med. 2015;372(14):1312-1323. doi:10.1056/NEJMoa1406330

Common Cell Shape Evolution Of Two Nasopharyngeal Pathogens, Frédéric J. Veyrier, Nicolas Biais, Pablo Morales, Nouria Belkacem, Cyril Guilhen, Sylvia Ranjeva, Odile Sismeiro, Gérard Péhau-Arnaudet, Eduardo P. Rocha, Catherine Werts, Muhamed-Kheir Taha, Ivo G. Boneca

Publications and Research

Respiratory infectious diseases are the third cause of worldwide death. The nasopharynx is the portal of entry and the ecological niche of many microorganisms, of which some are pathogenic to humans, such as Neisseria meningitidis and Moraxella catarrhalis. These microbes possess several surface structures that interact with the actors of the innate immune system. In our attempt to understand the past evolution of these bacteria and their adaption to the nasopharynx, we first studied differences in cell wall structure, one of the strongest immune-modulators. We were able to show that a modification of peptidoglycan (PG) composition (increased proportion of pentapeptides) …

Granulomatosis With Polyangiitis (Wegner’S) : Often Mistaken For Tuberculosis, Dawn Palumbo

Nursing Student Class Projects (Formerly MSN)

The exact cause of GPA has yet to be identified. Dinić et al. (2013) defines GPA/WG as “anti-neutrophil cytoplasmic antibodies (ANCAs)- associated systemic vasculitis of unknown etiology” (p. 887). According to Alam, Dastider, Ahmed, and Rabbani (2012) both cellular and humoral immunity are thought to be involved in the pathogenesis of wegener’s granulomatosis. “ The initial pathologic lesion is granuloma believed to be caused by cellular immune process. The strong association on C-ANCA with this disease suggests the role of humoral immunity” (Alam et al., 2014, p. 98). Huang et al. (2013) suggest, “The main pathological features of limited Wegeners’ …

Paradoxical Vocal Fold Motion, Stephen Sherer

Nursing Student Class Projects (Formerly MSN)

Paradoxical vocal fold motion (PVFM), otherwise known as vocal cord dysfunction (VCD) is an abnormal degree the vocal folds adduct upon inspiration causing airflow narrowing. This restriction can cause severe dyspnea and can be misdiagnosed as asthma. The cause of the abnormality related to PVFM has not been directly recognized, but multiple factors or triggers are associated. It is this lack of clarity and association with asthma, exercise, extubation, stress, and gastric reflux that I take interest in this pathology. I have a personal connection with exercise induced asthma. In addition, my sister in-law was recently diagnosed with VCD who …

Idiopathic Pulmonary Fibrosis: Understanding Has Led To Exciting Treatments, William Metz

Nursing Student Class Projects (Formerly MSN)

Pulmonary fibrosis can be described as an excessive amounts of fibrous connective lung tissue in the lung. Idiopathic pulmonary fibrosis(IPF) is the most common form of interstitial lung disease(ILD). When an obvious cause cannot be determined, a diagnosis of Idiopathic pulmonary fibrosis is made. The mean survival for patients is approximately 3-5 years from time of diagnosis. IPF is found primarily in men over 50 years of age, with a history of cigarette smoking with concurrent environmental and occupational inhalation exposures(Leslie, 2011, p. 592). Pulmonary fibrosis has been identified by early pathologists at the beginning of the last century. During …

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 …

Pneumonia: Not Getting Vaccinated May Take Your Breath Away, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

Impact Of Poor Air Quality On Chronic Respiratory Problems Among The Elderly, James D. Blando, My Ngoc Nguyen, Manasi Sheth-Chandra, Muge Akpinar-Elci

Community & Environmental Health Faculty Publications

[First Paragraph] There is a considerable body of evidence that suggests poor ambient air quality contributes to increased mortality and morbidity. ^1,2,3,4,5 The impact of ambient air quality on different segments of the general population, including children and among the elderly has also been investigated.^6,7,8,9 In light of the well documented public health significance of air pollution, it is imperative that investigators continue to evaluate details regarding the impact of poor air quality. In particular, it is interesting to note that some research has indicated an increased risk of the young and the elderly being admitted to the hospital …

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) …

Relaxation Techniques For People With Chronic Obstructive Pulmonary Disease: A Systematic Review And A Meta-Analysis, Eleonora Volpato, Paolo Banfi, Sheena M. Rogers, Francesco Pagnini

Dartmouth Scholarship

Chronic Obstructive Pulmonary Disease (COPD) people suffer from severe physical impairments, which often elicit significant psychological distress and impact their quality of life. This meta-analysis aimed to assess evidence from the scientific literature on the effects of relaxation techniques. Methods. We investigated 9 databases to select 25 RCTs. Studies included both inpatients and outpatients with COPD. Both respiratory and psychological outcomes were considered.

Is The Neuraminidase Inhibitor Tamiflu Effective In The Treatment Of Influenza?, Eliyakim Hershkop

The Science Journal of the Lander College of Arts and Sciences

Influenza is a disease that has caused the deaths of tens of millions people in the last century alone. The influenza neuraminidase protein is essential in the mechanism infection. It enables the virus to leave the infected cell and proliferate. Antiviral neuraminidase inhibitor drugs can be used for treatment. The drug Tamiflu is the standard of care for both treatment and prophylaxis of influenza. The Cochrane reports of 2009 and 2014 conclude that evidence is lacking to support this. Numerous bodies disagree. Cochrane also question the accuracy and credibility of many studies and agencies in support of Tamiflu. This paper …

Long-Term Effect Of Respiratory Training For Chronic Obstructive Pulmonary Disease Patients At An Outpatient Clinic: A Randomised Controlled Trial, Feng Xi, Zheng Wang, Yong Qi, Richard F. Brightwell, Peter Roberts, Angus Stewart, Wei Wang

Research outputs 2014 to 2021

Objective: To assess the effect of respiratory training (RT ) on lung function, activity tolerance and acute exacerbation frequency with chronic obstructive pulmonary disease (COPD). Design: A randomised controlled trial. Setting: Outpatient clinic and home of the COPD patients, Zhengzhou City, China. Subjects: Sixty participants with COPD were randomised into two groups: an intervention group ( n = 30) which received the RT in self-management and a control group ( n = 30) that received an education program during the study. Intervention: Pulmonary function, activity tolerance and frequency of acute exacerbation of these COPD patients were evaluated before and after …

Vitamin C: A Potential Regulator Of Inflammatory Response, Bassem M. Mohammed

Theses and Dissertations

Introduction: Neutrophils (PMNs) and Macrophages are the first responders recruited consecutively to the site of injury/inflammation. PMNs’ response/fate as well as macrophage reprogramming ultimately determine the course of resolution of inflammation. Physiologic wound healing has a significant inflammatory component. An exaggerated inflammation however is self-defeating leading to delayed healing. Parenteral vitamin C (VitC) attenuated inflammation in murine sepsis models and in patients with sepsis. However information about the mechanisms by which VitC regulates these events is limited.

Methods: Humanized mice lacking VitC synthesis capability (Gulo^-/-) were used. VitC sufficient and deficient mice were challenged with sterile inflammation, or …

Is Stimulating Acupoints On The Skin In Addition To Standard Medication More Effective For The Improvement Of Breathlessness In Ambulatory Patients With Copd Over The Age Of 60 Than Standard Medication Alone?, Abigail D. Sbat

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not stimulating acupoints on the skin in addition to standard medication is more effective for the improvement of breathlessness in ambulatory patients with COPD over the age of 60 than standard medication alone.

STUDY DESIGN: Review of three randomized controlled trials published in 2008, 2010, and 2012; selection was based on their relevance to the clinical question and if they contained patient oriented outcomes.

DATA SOURCES: Three peer-reviewed randomized controlled trials comparing the addition of acupuncture/Acu-Tens to standard treatment and standard treatment alone were found on PubMed. …