Chronic obstructive pulmonary disease (COPD) is an illness characterized by progressive respiratory symptoms and frequent exacerbations. Acute exacerbations of COPD (AECOPD) are mostly treated in the outpatient setting and the use of antibiotics for this patient population remains controversial. This thesis aimed to explore the role of antibiotics in the outpatient management of AECOPD through two studies. The first study was a systematic review of randomized controlled trials examining the impact of antibiotics on the outcome of treatment failure in outpatients with AECOPD. Meta-analysis was conducted using both frequentist random effects and Bayesian analyses. The second study was a secondary analysis of a prospective cohort of patients with AECOPD discharged from the emergency department. The association between antibiotic treatment and the outcome of rehospitalization within 14 days of discharge was examined using logistic regression and propensity score matched analyses. In the systematic review and meta-analysis, both frequentist random effects and Bayesian analyses revealed a high likelihood of benefit for antibiotics. In the secondary analysis, there was no association between treatment with antibiotics and rehospitalization however due to a small sample size and a low event rate, there was considerable risk of Type II error. Overall, when considering the results of these two studies in the context of previous literature, treatment with antibiotics likely provides a modest benefit in the outpatient management of AECOPD.

Cytotoxiques en lysant différents types de cellules et régulent la réponse immunitaire. Leur rôle dans l’asthme et ses exacerbations reste encore à identifier même si des modifications phénotypiques ont été observées chez des patients asthmatiques et qu’il a été récemment montré dans un modèle murin qu’elles n’intervenaient pas dans le développement de l’asthme allergique. L’objectif de la thèse était de mieux comprendre la place des cellules NK dans la pathologie asthmatique en se focalisant sur deux aspects : l’exacerbation viro-induite et l’inhibition par des composants microbiens.L’hypothèse pour la 1ère partie de la thèse était que les cellules NK de patients asthmatiques pouvaient présenter une dysfonction dans leur réponse à des agents microbiens qui pourrait favoriser l’exacerbation de la réaction asthmatique. Pour cela, nous avons analysé l’activation, la cytotoxicité et la production de cytokines de cellules NK provenant de patients asthmatiques sévères stimulées avec des molécules mimant des microorganismes ou un rhinovirus vivant (HRV), en comparaison avec des donneurs sains. Nous avons montré que les cellules NK de patients sévères étaient moins cytotoxiques que les cellules NK de donneurs sains en réponse à la stimulation avec un agoniste de Toll-Like Receptor 3 ou du TLR7/8 et avec HRV. En outre, lorsqu’elles sont stimulées avec de l’IL-12 et de l’IL-15, des cytokines produites pendant l’infection virale, les cellules NK de patients asthmatiques sévères expriment moins d’IFN-γ que les cellules NK de donneurs sains. Nos résultats suggèrent que l’activation des cellules NK de patients asthmatiques pourrait être insuffisante pendant les infections respiratoires et pourraient participer à l’aggravation de l’asthme.L’hypothèse pour la 2ème partie de la thèse était que les cellules NK pourraient participer à l’inhibition de la réaction asthmatique allergique dans un modèle murin. Dans des souris C57BL/6 sensibilisées à l’ovalbumine, l’instillation de FSL1, un agoniste de TLR2/6 inhibe la réaction asthmatique allergique. Cette inhibition étant associée à des modifications de la population des cellules NK, nous avons analysé leur rôle grâce à des souris déficientes en cellules NK. En l’absence de cellules NK, les souris développent un asthme allergique, et l’inhibition par FSL1 est maintenue. Par conséquent, les cellules NK ne jouent pas de rôle dans le développement de l’asthme allergique expérimental, ni dans son inhibition induite par un agent microbien. Cependant, elles pourraient être modifiées par l’environnement allergique, et avoir ainsi un rôle dans les exacerbation viro-induites. Cette question cruciale rejoint le travail réalisé dans la première partie de la thèse.En conclusion, nos résultats suggèrent que les fonctions des cellules NK seraient modifiées dans la pathologie asthmatique, qu’elle soit allergique ou non. Notre hypothèse est que le défaut d’activation des cellules NK participerait aux exacerbations viro-induites de l’asthme. Les perspectives de ces travaux sont de poursuivre la caractérisation des cellules NK chez les patients asthmatiques sévères et d’évaluer le rôle des cellules NK dans un modèle murin d’exacerbation de la réaction asthmatique.L’hypothèse pour la première partie de la thèse était que les cellules NK de patients asthmatiques pouvaient présenter une dysfonction dans leur réponse à des agents microbiens qui pourrait favoriser l’exacerbation de la réaction asthmatique. Pour cela, nous avons analysé l’activation, la cytotoxicité et la production de cytokines de cellules NK provenant de patients asthmatiques sévères stimulées avec des molécules mimant des microorganismes ou un rhinovirus vivant (HRV), en comparaison avec des donneurs sains. Nous avons montré que les cellules NK de patients sévères étaient moins cytotoxiques que les cellules NK de donneurs sains en réponse à la stimulation avec un agoniste de Toll-Like Receptor 3 ou du TLR7/8 et avec HRV [...] / Asthma is a chronic inflammatory disease of the airways affecting 334 million of people worldwide. Among asthma patients, 5% suffers from severe asthma. Severe asthma represents a major unmet need because, despite heavy treatments, patients still suffer from uncontrolled asthma symptoms, frequent exacerbations and a dramatic decrease in their respiratory capacity. The role of microorganisms in asthma is complex. On one hand, a group of epidemiologic and experimental studies have shown that chronic exposure with bacteria or microbial compounds, particularly during early childhood, would provide protection against allergic asthma. On the other hand, respiratory viruses are responsible for 80% of exacerbations and are associated with an increasing risk of developing asthma in children, whether allergic or not. Natural Killer cells (NK) are lymphocytes involved in innate antiviral immunity. They have cytotoxic functions by lysing different types of cells but also regulatory functions by producing cytokines and activating other immune cells. Their role in asthma and its exacerbations has yet to be identified, although phenotypic changes have been observed in asthmatic patients and it has recently been shown in a mouse model that they are not involved in the development of allergic asthma. The objective of the thesis was to better understand the role of NK cells in asthmatic pathology by focusing on two aspects : virus-induced exacerbation and inhibition by microbial compounds.The hypothesis for the first part was that NK cells from asthma patients may present a dysfunction in their response to microbial agents that could promote the exacerbation of the asthmatic reaction. To do this, we analysed NK cell activation, cytotoxicity and production of cytokines from severe asthmatic patients stimulated with molecules mimicking microbes or a human rhinovirus (HRV), compared to healthy donors. We showed that NK cells from severe asthma patients were less cytotoxic than NK cells from healthy donors in response to stimulation with a Toll-like Receptor 3 or TLR7/8 agonist and HRV. Moreover, when stimulated with IL-12 and IL-15, cytokines produced during viral infections, NK cells from severe asthma patient express less IFN-γ than NK cells from healthy donors. Our results suggest that the activation of NK cells in asthma patients may be insufficient during respiratory infections and may contribute to the worsening of asthma.The hypothesis for the second part was that NK cells may participate to the inhibition of a mouse model of allergic asthma. In C57BL/6 mice sensitized with ovalbumin, instillation of FSL1, agonist of TLR2/6, inhibits the features of experimental asthma. Since this inhibition is associated with changes in the population of NK cells, we analysed their role using mice deficient in NK cells. In the absence of NK cells, mice develop allergic asthma, and inhibition by FSL1 is maintained. Therefore, NK cells do not play a role in the development of experimental allergic asthma or in its inhibition induced by a microbial agent. However, they may be modified by the allergic environment, and thus have a role in viro-induced exacerbations. This crucial question is in line with the work done in the first part of the thesis.In conclusion, our results suggest that the functions of NK cells may be modified in asthmatic pathology, whether allergic or not. Our hypothesis is that the defect in NK cell activation may participate to virus-induced asthma exacerbations. Perspectives of this work are to further characterize NK cells in severe asthma patients and to evaluate the role of NK cells in a mouse model of asthma exacerbation.

Chronic obstructive pulmonary disease (COPD) patients are generally more sedentary and less physically active than healthy adults; putting them at increased risk of hospitalisation and death. For patients with mild-moderate COPD, physical activity appears to be reduced compared with apparently healthy adults but differences in time spent sedentary are less well established. Additionally, there is a need for a greater understanding of the correlates of behaviour in mild-moderate patients with much of the existing literature focusing on more severe or mixed stage patient samples and with many studies lacking objective behavioural monitoring, not adjusting for confounders and a paucity of data on correlates of sedentary time. Despite having mild-moderate airflow obstruction, these patients also report a range of symptom burdens with some individuals reporting severe symptoms. Subsequently, these patients represent a sub-set of individuals who may require lifestyle interventions. Therefore, factors associated with patients reporting more severe symptoms need to be identified to help understand how this phenomenon may manifest and be intervened upon. For patients with more advanced COPD who are admitted to hospital for an acute exacerbation behavioural intervention focussing on less intense movement may be a more suitable approach for reducing the risk of readmissions than more intense physical activity or exercise. To date no studies have specifically targeted reductions in sedentary behaviour in COPD. In addition, wearable self-monitoring technology may facilitate the provision of such interventions, removing important participation barriers such as travel and cost, but this has not been sufficiently examined in COPD. This thesis investigated: (i) objectively measured physical activity and sedentary time and the correlates of these behaviours for mild-moderate COPD patients and apparently healthy adults (Study One); (ii) factors associated with self-reported symptom severity and exacerbation history in mild-moderate COPD patients (Study Two) and (iii) the feasibility and acceptability of a home-based sedentary behaviour intervention using wearable self-monitoring technology for COPD patients following an acute exacerbation (Study Three). Methods: Study One: COPD patients were recruited from general practitioners and apparently healthy adults from community advertisements. Objectively measured moderate-to-vigorous physical activity (MVPA), light activity and sedentary time for 109 mild-moderate COPD patients and 135 apparently healthy adults were obtained by wrist-worn accelerometry. Patients with at least four valid days (≥10 waking hours) out of a possible seven were included in analysis. A range of demographic, social, symptom-based, general health and physical factors were examined in relation to physical activity and sedentary time using correlations and linear regressions controlling for confounders (age, gender, smoking status, employment status and accelerometer waking wear time). Study Two: In 107 patients recruited from general practitioners, symptoms were assessed using the COPD Assessment Test (CAT) and Modified Medical Research Council (mMRC) questionnaires. Twelve-month exacerbation history was self-reported. Exercise capacity was assessed via incremental shuttle walk test (ISWT) and self-reported usual walking speed. Physical activity and sedentary time were obtained from a wrist-worn accelerometer. Study Three: Patients were randomised in-hospital into a usual care (Control), Education or Education + Feedback group with the intervention lasting 14 days following discharge. The intervention groups received information about reducing prolonged sitting. The Education + Feedback group also received real-time feedback on their sitting time, number of stand-ups and step count at home through an inclinometer linked to a smart device app. The inclinometer also provided vibration prompts to encourage movement when the wearer had been sedentary for too long. Feasibility of recruitment (e.g. uptake and retention) and intervention delivery (e.g. fidelity) were assessed. Acceptability of the intervention technology (e.g. wear compliance, app usage and response to vibration prompts) was also examined. Results: Study One: COPD patients were more sedentary (592±90 versus 514±93 minutes per day, p < 0.05) and accrued less MVPA (12±18 versus 33±32 minutes per day, p < 0.05) than apparently healthy adults. For COPD patients, self-reported dyspnea and percentage body fat were independent correlates of sedentary time and light activity with exercise capacity (incremental shuttle walk test) an independent correlate of MVPA. For apparently healthy adults, percentage body fat and exercise capacity were independent correlates of sedentary time and light activity. Percentage body fat was an independent correlate of MVPA. Study Two: ISWT (B=-0.016±0.005, partial R2=0.117, p=0.004) and years living with COPD (B=0.319±0.122, R2=0.071, p=0.011) were independently associated with CAT score. ISWT (B=-0.002±0.001, R2=0.123, p < 0.001) and vector magnitude counts per minute (VMCPM) (B=0.0001±0.0000, R2=0.050, p=0.011) were independently associated with mMRC grade. MVPA was independently associated with previous exacerbations (B=-0.034±0.012, R2=0.081, p=0.005). Patients reporting a CAT score of > 20 or an mMRC score of ≥2 had lower VMCPM, were more sedentary and took part in less light activity than patients reporting a CAT score of 0-10 or mMRC of 0, respectively. Patients reporting ≥2 exacerbations took part in less MVPA than patients reporting zero exacerbations. Study Three: Study uptake was 31.5% providing a final sample of 33 COPD patients. Retention of patients at two-week follow-up was 51.5% (n=17). Reasons for drop-out were mostly related to being unable to cope with their COPD. Patients wore the inclinometer for 11.8±2.3 days (and charged it 8.4±3.9 times) with at least one vibration prompt occurring on 9.0±3.4 days over the 14 day study period. Overall, 325 vibration prompts occurred with patients responding 106 times (32.6%). 40.6% of responses occurred within 5 minutes of the prompt with patients spending 1.4±0.8 minutes standing and 0.4±0.3 minutes walking, taking 21.2±11.0 steps. Discussion: Study One: COPD patients were less active and more sedentary than apparently healthy adults; however, factors predicting behaviour were similar between groups. Correlates differed between sedentary time, light activity and MVPA for both groups. Interventions to boost physical activity levels and reduce sedentary time should be offered to patients with mild-moderate COPD, particularly those reporting more severe breathlessness. Study Two: Worse exercise capacity, low levels of physical activity and more time spent sedentary are some of the factors associated with patients of the same severity of airflow limitation reporting differing symptom severities. These patients may benefit from both lifestyle and exercise interventions. Study Three: Recruitment and retention rates suggest a trial targeting sedentary behaviour in hospitalised COPD patients is feasible. A revised intervention, building on the successful components of the present feasibility study is justified. Conclusion: The findings from this thesis have contributed a greater understanding of physical activity and sedentary behaviour in COPD and can inform the development of tailored physical activity and sedentary behaviour interventions for patients across the grades of COPD severity.

Class of 2017 Abstract / Objectives: The objective of this retrospective cohort chart review was to evaluate the safety and efficacy of extended infusion beta-lactam regimens as part of treatment of acute CF pulmonary exacerbations in adults and pediatric patients. Methods: Inclusion criteria: adult and pediatric patients (age 1 month or older) with CF diagnosis who were admitted to BUMC-T for acute pulmonary CF exacerbation, and who received meropenem, imipenem, aztreonam, piperacillin-tazobactam, and or cefepime during their hospitalization (between 1/1/2011 and 10/30/2015). Exclusion criteria: pregnant women and admissions less than 24 hours. The two groups evaluated were patients receiving treatment (group 1) prior to extend infusion practices (Jan 2011 – Dec 2012) and (group 2) after implementation of extend infusion practices (Jan 2013 – Oct 2015). Data was collected from medical records using both the Sunrise Clinical Manager and EPIC electronic medical record systems. The data was then analyzed for differences in efficacy outcomes (e.g., length of hospitalization, lung function, return to baseline lung function), changes in renal and hepatic function, incidence of documented adverse drug effects, and potential factors associated with increased risk for changes in renal or hepatic function with use of extended infusion beta‐lactam regimens. Results: Pending. Efficacy outcomes: - length of hospitalization - improvement in lung function - return to baseline lung function Safety outcomes: - changes in renal and hepatic function - incidence of documented adverse drug effects - potential factors associated with increased risk for changes in renal or hepatic function Conclusions: Pending. As this study is being conducted at one academic medical center, conclusions may not be generalizable to other institutions.

Background: COPD is characterised by increased neutrophilic inflammation which further increases during exacerbations. Corticosteroids are currently one of the mainstays of treatment but they have limited effectiveness; there is a great need to develop new anti-inflammatory pharmacotherapies for use in COPD. Inhaled LPS has been used as a model of increased neutrophilic inflammation in healthy patients, smokers and asthmatics. Its use in patients with COPD as a model of exacerbations has not yet been evaluated. PI3 kinase is a vital intracellular enzyme, which upon activation leads to a number of cellular processes; the γ and δ isoforms of the enzyme are of particular importance in leucocyte migration, development and activation. There is increasing evidence for upregulation of this pathway in COPD.Aims: (1) To test the safety of the use of inhaled LPS in patients with COPD for use as a model of exacerbation and to investigate the systemic and airway inflammatory response in vivo. (2) To investigate the action of PI3 kinase enzyme inhibitors and dexamethasone in vitro on neutrophilic inflammation in COPD patients during the stable state and exacerbations. Methods: (1) 12 patients with mild to moderate COPD inhaled 5µg LPS; safety measurements and airway and systemic biomarkers were collected up to 24 hours post inhalation. (2) The effect of PI3 kinase enzyme inhibitors and dexamethasone on MMP-9 and ROS release from peripheral and airway neutrophils from stable COPD and exacerbations was examined in vitro. The effect of PI3 kinase enzyme inhibitors and dexamethasone on cytokine release from peripheral neutrophils from stable COPD patients was also investigated. Results: (1) Inhaled LPS (5µg) caused a significant fall in FEV1 and increase in sputum neutrophil numbers. There was an associated increase in systemic IL-6, CRP and CC-16, all with differing temporal patterns. No patients reported any significant symptoms. (2) PI3 kinase enzyme inhibitors significantly reduced MMP-9 and ROS release from airway and peripheral neutrophils from COPD patients in the stable state and during exacerbations; dexamethasone had minimal effect. Cytokine release from peripheral neutrophils from COPD patients in the stable state was also significantly inhibited by PI3 kinase enzyme inhibitors and dexamethasone. Conclusions: (1) Inhaled LPS in patients with COPD is a safe model to induce acute on chronic neutrophilic inflammation and therefore could be used as a model to study COPD exacerbations. (2) PI3 kinase enzyme inhibitors reduce COPD neutrophil MMP-9, ROS and cytokine release in vitro and are therefore are a promising new anti-inflammatory pharmacotherapy.

Bakgrund: Kronisk obstruktiv lungsjukdom (KOL) är en av de vanligaste dödsorsakerna i världen. KOL är en kronisk sjukdom som är icke reversibel och orsakas främst av tobaksrökning. En vanlig komplikation vid KOL är exacerbationer. Detta försämringstillstånd ger tilltagande symtom och kan orsaka ökat vårdbehov. Syfte: Att sammanställa och beskriva upplevelser av exacerbationer för personer med KOL. Metod: En litteraturstudie med deskriptiv design. Genom databasen PubMed identifierades 12 vetenskapliga artiklar som bemötte litteraturstudiens inklusionskriterier och användes i studiens resultat. Huvudresultat: I resultatet framkom två huvudteman: ”Upplevelser av symtom” och ”Hantering”. Deltagare från valda studier framhävde olika upplevelser, hanteringsstrategier och påverkan av exacerbationer. Slutsats: KOL-exacerbationer har en negativ inverkan på den fysiska och psykiska förmågan samt sociala relationer. Personer som drabbats av exacerbationer tvingades anpassa sin vardag efter sjukdomens progression. Upplevelserna påverkades av deltagares kunskapsnivå om KOL generellt och vikten av att utföra egenvård. Individerna använde sig av olika strategier för att förebygga och hantera symtom som uppkom vid exacerbationer. Tankar som uppkom under exacerbationerna medförde en ökad motivation till livsstilsförändringar. Fortsatt forskning och utbildning om personers upplevelser av KOL-exacerbationer bidrar till ökad kunskap. Den grundutbildade sjuksköterskan kan genom ökad kunskap lättare anpassa sitt bemötande och utforma omvårdnaden efter personens individuella behov. / Background: Chronic obstructive pulmonary disease (COPD) is one of the most common causes of death in the world. COPD is a chronic disease that is irreversible and is mainly caused by tobacco smoking. A common complication of COPD is exacerbations. This state of deterioration causes increasing symptoms and can cause an enhanced need for care. Purpose: To compile and describe the experiences of exacerbations by people’s with COPD. Method: A literature study with a descriptive design. By using the PubMed database, 12 articles were identified that met the literature study's inclusion criteria’s and were used in the study's result. Main results: In the results, two main categories emerged: "Experiences of symptoms" and "Management". Participants from selected studies described different experiences, coping strategies and impact of exacerbations. Conclusion: COPD exacerbations have a negative impact on physical and mental ability as well as social relationships. People that are affected by exacerbations were forced to adapt their everyday life to the progression of the disease. The experiences were influenced by participants' level of knowledge about COPD in general and the importance of performing self-care. Individuals used different strategies to prevent and manage symptoms that occurred during exacerbations. Thoughts that came during the exacerbations led to an increased motivation for lifestyle changes. Continued research and education about people's experiences of exacerbations can contribute to increased knowledge. Through increased knowledge, nurses can more easily adapt the treatment and design the care to the person's individual needs.

The aim of this thesis was to modify and evaluate effects, as well as todescribe experiences of a nurse-led multidisciplinary programme of pulmonaryrehabilitation in primary health care for patients with chronicobstructive pulmonary disease (COPD) and their next of kin.Interviews were performed with 12 COPD nurses about their experiencesof patient education (I). Forty-nine patients participated in the interventiongroup and 54 in the control group in a quasi-experimentalstudy which investigated the effects of the programme on functional capacity,quality of life and exacerbation frequency during one year (II).Interviews were performed related to the experiences of 20 patients whohad participated in the six-week programme (III) and the experiences of20 next of kin to the patients that had participated (IV).The results showed that COPD nurses fluctuated between security andinsecurity in patient education and were in need of support, time, structureand collaboration to develop their patient education (I). In Study IIthere were no differences between the groups with regard to functionalcapacity and quality of life, but the number of exacerbations decreased inthe intervention group and increased in the control group (II). The patientsin study III had allowed themselves to live at their own pace followingthe programme but a constant fear was present in spite of the programme(III). Next of kin in Study IV had a life that remained overshadowedby illness but there were positive outcomes of the programme aslong as two years afterwards. The next of kin also had constant fear,however (IV).In conclusion, the six week programme brought about results in changingeveryday life. Nevertheless, all lived in the shadow of fear and uncertaintyin spite of the programme. More research is needed to address therequirements of COPD nurses, patients and next of kin.

Introduction Asthma is a common and heterogeneous disease in primary care. Asthma phenotypes are recognisable clusters of for example clinical characteristics. Current asthma symptoms and previous exacerbations are used to assess the level of asthma control. Asthma control is used clinically to plan follow-up strategies. Aim The aim of this study is to examine if an data-driven algorithm based on sex and age of onset can categorize an asthma population at a primary care center into three phenotypes with different risk of disease. To investigate if the results can be generalized by comparing to an epidemiological survey in Sweden. Secondary aims are to investigate if these phenotypes predict the level of follow-up and which factors influence asthma control. Methods In this cross-sectional study, 335 participants from one primary care site and 1442 participants from an epidemiological study were compared on sex, age, medical treatment, respiratory allergy, smoking, asthma symptoms and exacerbations. Logistic regression analyses focusing on factors affecting asthma control were performed in a consolidated dataset. Results An adult asthma population can easily be categorized according to the data-driven algorithm. However, these phenotypes do not predict follow-up strategies. Clinical follow-up based on level of asthma control, did not differ between the phenotypes. There were statistically significant differences between the phenotypes regarding respiratory allergy and smoking. In the logistic regression, smoking has the highest odds for poor asthma control. Conclusion The clinical use of the data-driven phenotypes were limited. Follow-up strategies are probably best based on traditional clinical outcomes like asthma control.

Cystic fibrosis (CF) is an autosomal recessive disorder affecting 70,000 individuals worldwide. This disease is characterized by the buildup of mucus in the airways leading to chronic lung infections resulting in pulmonary failure and death in 95% of CF patients. Routine surveillance of CF pathogens using traditional microbiology culture guides management and treatment of CF patients. Molecular profiling studies have revealed emerging pathogens that may play a role in CF lung disease by either directly causing infection or upregulating the virulence factors of classic CF pathogens, such as P. aeruginosa; however, routine CF culture protocols have not been modified to detect these organisms. The goal of this study was to expand the data relevant to the use of microbiology cultures for the management and treatment of CF patients at Virginia Commonwealth University Medical Center (VCUMC) by directly selecting for emerging CF pathogens in culture. This was accomplished by developing,optimizing, and implementing an agar to select for colistin-resistant non-fermenting Gram- negative rods (NF GNRS). In addition, McKay agar and anaerobic media were utilized to recover members of the Streptococcus anginosus group (SAG) and anaerobes in CF respiratory samples. The prevalences of SAG, anaerobes, and colistin-resistant NF GNRs recovered on study media from 75 adult and pediatric CF patients at VCUMC were 17.33%, 41.33%, and 4% respectively. Approximately 62% of patients culture-positive for SAG were also infected with P. aeruginosa and 53.8% of SAG recovered in culture were from CF patients experiencing PE. These findings further support the claim that interspecies interactions among emerging and classic CF pathogens may result in periods of clinical instability or PE. Twenty-eight of the 75 patients were culture-positive for Veillonella species, with the majority of samples collected during a period of surveillance. Four colistin-resistant NF GNRs were isolated on the study media alone. The selective nature of the study media prevented the mixed respiratory flora and classic CF pathogens from overgrowing and obscuring the growth of these colistin-resistant NF GNRs. The presence and role of emerging pathogens in the CF patient population at VCUMC warrants further investigation; therefore, the routine culture protocol needs to be revised to recover and select for those organisms thought to play a role in PE and lung function decline.

Elderly patients with chronic obstructive pulmonary disease may be at increased risk of exacerbation due to physical and cognitive deficits that make proper inhaled medication adherence more difficult despite consistent medication access. This retrospective study utilized administrative medical and pharmacy claims data to examine the likelihood of having a COPD exacerbation requiring acute medical care by means of an emergency room visit or hospitalization in elderly patients receiving maintenance COPD medications from mail order and retail pharmacies. It was hypothesized that mail order patients would be more likely to experience exacerbations despite differences in medication access when compared to retail patients. The primary outcome of interest was exacerbation frequency expressed as the incidence density rate, and the secondary outcome was the proportion of days covered (PDC). The incidence rate ratio for acute exacerbations was not significantly different for mail order and retail groups, indicating patients using mail-order pharmacies were not significantly more likely to experience an exacerbation requiring acute medical care. Despite insignificant differences in incidence rates, mail order patients had significantly higher adherence rates.