This project focused on the pulmonary application of magnetic resonance (MR) quantitative equilibrium signal (qS0) mapping, dynamic oxygen-enhanced (OE-) magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE-) MRI in asthma and chronic obstructive pulmonary disease (COPD). Initially, a retrospective analysis of MRI and X-ray computed tomography (CT) data from 24 COPD patients and 12 healthy controls demonstrated that MR qS0 mapping had good one-week reproducibility and was comparable to CT in the localization and quantification of emphysema in patients with COPD. In the same data, a reduced oxygen (O2) delivery signal was detected by dynamic OE-MRI in COPD patients regardless of the presence or absence of emphysema on CT, while a significantly reduced baseline spin-lattice relaxation time (T1air) was only observed in emphysematous COPD. Emphysematous COPD also showed significant correlations between dynamic OE-MRI readouts, i.e. enhancing fraction (EF) and the change in the partial pressure of O2 in lung parenchyma (ΔPO2max), and pulmonary diffusion capacity and CT estimates of emphysema. A prospective pilot study was conducted in 10 asthmatic patients which demonstrated that dynamic OE-MRI readouts, including EF, ΔPO2max and O2 wash-in time constant (τup), were reproducible within one month, sensitive to asthma severity and strongly correlated with spirometric readouts of airway function and lung volume. This was followed by a second prospective intervention study in 30 asthmatic patients and 10 healthy controls which revealed a pattern of decreased O2 delivery signal as a response to salbutamol inhalation in severe asthmatics but not in mild asthmatics or healthy controls using short-term repeated dynamic OE-MRI. In addition, DCE-MRI was also performed on 30 asthmatic patients and 10 healthy subjects. A semi-quantitative analysis demonstrated that contrast agent kinetics in asthmatic lungs were characterised by a reduced first-pass peak (SI%max) and a shallower downslope during the late redistribution phase (kwashout) than was observed in healthy controls, and that these were related to pulmonary function test measurements. An extended Tofts model-based quantitative analysis further revealed a significantly increased fractional extravascular extracellular space (ve) in patients with asthma than in healthy controls while the contrast agent transfer coefficient (Ktrans), an index related to vascular permeability, and the fractional blood plasma volume (vp), did not distinguish asthmatics from controls. In conclusion, this project demonstrated the promise of 1) MR qS0 mapping for the assessment of emphysema in COPD lungs, 2) dynamic OE-MRI for the assessment of impaired pulmonary oxygenation in COPD and asthma and for the monitoring of short-term treatment effects in asthma and 3) DCE-MRI for the evaluation of pulmonary microvascular inflammation in asthma. The non-invasive non-ionizing properties and simple setup requirements make these three proton MRI techniques attractive options in the assessment of structural and functional alterations of the lungs in asthma and COPD in clinical settings.

This thesis examined associations between ecological indicators of residential radon and fine particulate matter air pollution (PM2.5) and lung cancer mortality using data from the American Cancer Society Cancer Prevention Study-II (CPS-II) prospective cohort. Nearly 1.2 million CPS-II participants were recruited in 1982. Mean county-level residential radon concentrations were linked to study participants according to ZIP code information at enrollment (mean (SD) = 53.5 (38.0) Bq/m3). Cox proportional hazards regression models were used to obtain adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for lung cancer mortality associated with radon. After necessary exclusions, a total of 811,961 participants in 2,754 counties were retained for analysis. A significant positive linear trend was observed between categories of radon concentrations and lung cancer mortality (p = 0.02). A 15% (95% CI 1 - 31%) increase in the risk of lung cancer mortality was observed per each 100 Bq/m3 radon. Radon was also positively associated with chronic obstructive pulmonary disease mortality (HR per each 100 Bq/m3 = 1.13, 95% CI 1.05 - 1.21). No clear associations were observed between radon and non-respiratory mortality. In lifelong never smokers (n = 188,699), each 10 µg/m3 increase in mean metropolitan statistical area PM2.5 concentrations was associated with a 15-27% increase in the risk of lung cancer death which strengthened among individuals with a history of asthma or any prevalent chronic lung disease at enrollment (p for interaction < 0.05). There was no association between PM2.5 and mortality from non-malignant respiratory disease. In conclusion, this thesis observed significant positive associations between ecological indicators of residential radon and PM2.5 concentrations and lung cancer mortality. These findings further support efforts to reduce radon concentrations in homes to the lowest possible level and strengthens the evidence that ambient concentrations of PM2.5 measured in recent decades are associated with small but measurable increases in lung cancer mortality. Further research is needed to better understand possible complex inter-relationships between environmental risk factors, chronic lung disease, and lung cancer.

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-06-19T18:07:19Z No. of bitstreams: 1 Patricia Lira dos Santos.pdf: 1133585 bytes, checksum: 6490c7c925c5ee032b1b041fe03ca427 (MD5) / Made available in DSpace on 2018-06-19T18:07:19Z (GMT). No. of bitstreams: 1 Patricia Lira dos Santos.pdf: 1133585 bytes, checksum: 6490c7c925c5ee032b1b041fe03ca427 (MD5) Previous issue date: 2015-12-17 / Introduction: It is not established at literature whether there is difference of the speed in ISWT carried out on treadmill (ISWTI-T) or corridor. Objective: To compare the speed, walked distance and cardiopulmonary responses between SWTI carried out on treadmill versus corridor. Methods: Thirty four volunteers with COPD [19 mens; 50 ± 17 % prev; age (63 ± 13)], were submitted to four tests (two ISWT-C and two ISWT-T), the ISWT-C was carried out according to original definition. The ISWT-T was carried out on an automatic treadmill, the speed increase of ISWT-C was carried to the ergometer. Both tests were carried out twice, in different days and randomized. The oxygen consumption (VO2peak), carbon dioxide production (VCO2), minute ventilation (MV), cardiac frequency (CF) and pulse oxygen saturation (SpO2) were measured during the tests continuously. Additionally, Borg dyspnea (Borg D) and Borg lower members fatigue (Borg MI) were registered at the beginning and end of the tests.Results: There was difference in walked distance (ISWT-T 371± 181 vs ISWT-C 295 ± 149, p=0,001) and speed (ISWT-T 3,5km/h vs ISWT- C 3,2km/h, p=0,010). Additionally, Borg MI, VE/VCO2 and VE/VO2 were higher in ISWT-C (p<0,05). Others variables, CF, Borg D, MV, MVV and VCO2 , were similar in both tests (p>0,05). Conclusions: The SWTI carried out on treadmill results in more walked distance and consequently, more speed reached. The ISWT treadmill and corridor are not interchangeable. / Introdução: Não está definido na literatura se existe diferença na velocidade atingida no SWTI se for realizado na esteira (SWTI-E) ou corredor (SWTI-C). Objetivos: Comparar a velocidade, distância percorrida e as respostas cardiopulmonares entre SWTI realizado na esteira e no corredor. Método: Trinta e quatro voluntários com DPOC [19 homens; VEF1 50 ± 17 % prev; idade (63 ± 13)], foram submetidos a quatro testes (dois SWTI-C e dois SWTI-E), o teste SWTI-C foi realizado segundo definição original. O SWTI-E foi realizado em uma esteira motorizada, o incremento de velocidade do SWTI-C foi transportado para o ergômetro da esteira. Ambos testes foram realizados duas vezes, em dias diferentes e de forma aleatória. O consumo de oxigênio (VO2pico), produção de gás carbônico (VCO2), ventilação minuto (VE), frequência cardíaca (FC), e saturação de pulso de oxigênio (SpO2) foram medidos continuamente durante os testes. Adicionalmente, Borg Dispneia (Borg D) e Borg fadiga de membros inferiores (Borg MI) foram registrados no início e final dos testes; Resultados: Houve diferença na distância percorrida (SWTI-E 371± 181 vs SWT-C 295 ± 149, p=0,001) e velocidade (SWT-E 3,5km/h vs SWTI- C 3,2km/h, p=0,010). Adicionalmente, o Borg MI, VE/VCO2 e VE/VO2 foram superiores no SWTI-C (p <0,05). Demais variáveis, FC, Borg D, VE, VVM e VCO2, foram similares em ambos testes (p > 0,05). Conclusões: O SWTI realizado na esteira resulta em maior distância percorrida e, consequentemente, maior velocidade atingida. O SWTI realizado na esteira e corredor não são intercambiáveis.

An improved understanding of the mucus biophysical alteration in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) patients is a milestone towards a more accurate and effective treatment of these common and highly debilitating conditions. Little is known about the variations in mucus structure between ill and healthy individuals. An established fact, however, is the role of the mucus obstruction in the exacerbation of the two conditions which impairs the physiological cleaning mechanism of the airways (mucociliary clearance) and is assessed as the strongest predictor of mortality. Therefore, it appears relevant to investigate which properties and structural changes are responsible of the impaired clearance of airway mucus. This thesis presents investigations of mucus on the basis of mucin structure observed in healthy, COPD and cystic fibrosis bronchial mucus samples. AFM (atomic force microscopy) and synchrotron SAXS (small angle X-ray scattering) techniques were used to characterise the structural features of the mucin molecules and allowed to identify the dumbbell structure of airways mucin monomers. The analysis of structural and dimensional features of mucins, highlighted a greater similarity of COPD with the healthy sample rather than with cystic fibrosis. The water sorption analysis using QCM-D (quartz crystal microbalance with dissipation monitoring), established a divergent behaviour between COPD and cystic fibrosis. Compared to healthy specimen, the mucus from COPD donors, showed a greater tendency to absorb water while cystic fibrosis mucus, in contrast, displayed the lowest water absorption.

BACKGROUND SUMMARY: Pulmonary rehabilitation programs are an important component of the multidisciplinary approach to minimizing the symptomatology of patients with chronic obstructive pulmonary disease. Within the program, patients learn about how to live with their non-curable disease and how to minimize exacerbations. Although patients learn about their disease process, breathing techniques, and exercise, there are no specific components that bridge the mind and body gap to promote mindfulness through the patients’ efforts within the program. LITERATURE REVIEW FINDINGS: This thesis contains a comprehensive literature review composed largely of randomized trials. These trials and studies summarize the framework of pulmonary rehabilitation programs and how yoga is implemented within treatment options for chronic diseases. The literature review highlights that pulmonary rehabilitation programs improve the quality of life in patients with emphysema through patient education on breathing and exercise. However, there is a lack of literature on the use of yoga techniques of breathing and exercise within the framework of pulmonary rehabilitation programs to promote mindfulness when living with a chronic disease. PROPOSED PROJECT: This thesis proposes a randomized controlled study to identify a more mindful approach to a pulmonary rehabilitation program for emphysema patients through the use of timed ujjayi pranayama (mindful breathing) and yoga asanas (poses). CONCLUSIONS: The results will be analyzed to determine if yoga techniques lead to statistically significant improvement in patient outcomes in emphysema patients enrolled in a pulmonary rehabilitation program. SIGNIFICANCE: The compiled data will reveal how yoga breathwork and movement will be beneficial for emphysema patients enrolled within a pulmonary rehabilitation program.

OBJECTIVE: The purpose of this study is to determine if there are any acoustic variables that can determine compromised lung function in patients with asthma and COPD. METHODS: This study involved using mobile and wearable technology to record voice and respiratory changes during various speaking and breathing tasks before and after administration of albuterol. Collaborators at Samsung Research America, Inc. used algorithms to measure pause time, pause frequency, respiratory rate, and inhale:exhale ratio. These variables were correlated with spirometry values before and after albuterol to assess clinical significance. RESULTS: We identified several acoustic markers that significantly correlate with lung function in patients with asthma and COPD. In particular, we found that the ratio of the one-second forced expiratory volume to forced vital capacity (FEV1/FVC) after administration of albuterol significantly correlated with the inhale:exhale ratio in asthma patients during the tidal breathing task. The post-albuterol FEV1/FVC significantly correlated with the inhale:exhale ratio in COPD patients during the supine breathing task. The pre-albuterol FVC significantly correlated with the pause frequency in asthma patients during the scripted speech task. CONCLUSION: The results in this study indicate that pause frequency and inhale:exhale ratio may be important biomarkers for identifying a respiratory illness, such as asthma and COPD. More research needs to be done using digital health to monitor disease symptoms with a larger sample size.

Chronic obstructive pulmonary disease (COPD) signifies a significant public health challenge that is both avoidable and treatable. There was no standardized education offered to the COPD population at the practice location. The scope of the project encompassed standardizing education by developing a self-management packet for the COPD patients. The goal of this project was to examine how the development of a standardized COPD self-management packet enhances the quality of care and strategizes reducing 30-day readmissions compared to nonstandardized delivery of education. Orem's self-care theory and Bandura's self-efficacy concept were used to explain the principle of self-management, while Rosswurm and Larrabee's evidence-based practice model was used to guide practice change. The U.S. Prevention Service Task Force's level of evidence hierarchy was chosen to categorize the strengths and weaknesses of the evidence referenced for this project. Postdevelopment surveys using the Likert scale were distributed to the facility's COPD committee, and a 70% response rate of strongly agreed to all questions was achieved. There were no adverse responses, and the packet was approved unanimously. Based on the positive responses, the packet will be easily adapted and beneficial in practice. The recommendation is to pilot the packet on the medical-surgical unit and follow-up postdischarge with phone calls to ascertain patients' perspective of the packet. Utilization of the education packet will lead to positive social change by affording the stakeholders self-management awareness and positive outcome measures including reducing the COPD 30-day readmission rate, curtailing economic strains, and promoting positive patient-centered relationships.

Chronic obstructive pulmonary disease (COPD), a progressive and nonreversible disease, is a leading cause of mortality and morbidity throughout the world. Detecting COPD early in the disease process will help in decreasing later stage COPD severity. Because airway inflammation is a hallmark of COPD, it has been proposed that measuring exhaled nitric oxide, a marker of inflammation, in exhaled breath condensate could prove to be an inexpensive and efficient method to detect COPD in outpatient settings. Using the hypothetico-deductive theory as a guideline, this study used secondary data from the National Health and Nutrition Examination Survey 2007 to 2010 to test the association between exhaled nitric oxide (eNO), COPD, and COPD severity. In addition, this study explored whether occupation modifies the association between eNO and COPD. Descriptive statistics, chi-square analyses, and regression analyses were used to analyze data from a sample size of 10,214 individuals. The prevalence of COPD was 7.2%, based on self-reported physician diagnoses and 11.4% based on prebronchodilator spirometry analysis, strengthening the argument that COPD is often under- or misdiagnosed in clinical settings. This study found no statistically significant association between eNO, COPD, and COPD severity, and occupational status did not appear to modify the association between eNO and COPD. The findings of this study highlight the importance of using objective measures such as spirometry in clinical settings for early diagnosis and management of COPD. Early diagnosis helps to slow the progression of the disease, resulting in fewer related comorbidities and complications.

Indiana University-Purdue University Indianapolis (IUPUI) / Chronic obstructive pulmonary disease (COPD) is a significant worldwide cause of chronic illness and mortality and one of the most common admitting diagnoses in the United States. Persons with COPD are at increased risk for deconditioning during hospitalization, which can lead to decreased functional status at discharge. Disease-related factors and elements of the hospital environment make older adults with COPD vulnerable to hospital-associated functional status decline. The purpose of this dissertation was to identify activity factors that contribute to hospital-associated functional status decline in older adults with COPD by promoting functioning during hospitalization. This predictive correlational study is a secondary analysis of a pre-existing dataset. Patients with COPD were pulled from the larger parent study sample for comparison with patients without COPD. The convenience sample consisted of 111 patients with COPD and 190 patients without COPD. Subjects were 46.5% male, 53.5% female, and a mean age of 66 years. All subjects were patients admitted to a pulmonary unit and received an intervention protocol designed to address mobility barriers related to COPD and hospitalization. Statistical analysis explored the number, type, and timing of activity events in relation to the selected functional status outcomes of discharge disposition, length of hospital stay, and 30-day readmission rates for hospitalized older adults with COPD. Multivariate and bivariate analyses results indicated ambulation to the bathroom, ambulation outside the patient room, and number of days to first out-of-bed activity were significant predictors (p < 0.05) of patient discharge to home; days to first activity and ambulation were significant predictors (p < 0.05) of reduced length of stay; none of the variables were predictive of 30-day readmission. Patients with COPD experienced longer lengths of stay and more non-weight bearing activity than patients without COPD in this sample. These findings provide a foundation for future research to explore hospital environmental factors influencing mobility, determine optimal modes of activity during hospitalization, and examine potential cost savings associated with promotion of early mobility. Findings help explain the effects of physical activity during hospitalization and may aid development of nursing interventions to prevent or alleviate functional status decline in this vulnerable population. / 2 years

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by breathlessness due to airflow obstruction. COPD is the third leading cause of death worldwide. So far, none of the existing pharmacological treatments for COPD can stop the progressive decline in lung function. Drug repurposing is the application of existing approved therapeutic compounds for new disease indications, which may reduce the cost and time of new drug development. So far, there is not any systematic multi-omics data integration for drug repurposing in COPD. The goal of this project is to develop a systems biology pipeline for the identification of biological-relevant gene targets with drug repurposing potential for COPD treatment using multi-omics integration. Here we implemented a computational methodology to identify drug repurposing targets for COPD. We integrated multi-omics COPD data including, genome, transcriptome, proteome, metabolome, interactome data, and drug-target information. A distance-based network model was created to rank the potential candidate genes. Fifty genes were prioritized as COPD signature genes for their overall proximity to signature genes identified at all omics levels. Forty of them may be considered as “druggable” targets. Literature search reported CRCX4 – Plerixafor as one prioritized targets-gene pair for drug repurposing. The bone marrow stimulant Plerixafor is currently being evaluated for COPD treatment in clinical trials, suggesting that our pipeline is finding promising drug repurposing targets. Our work, for the first time, applied a systematic approach integrating multiple omics data to find drug repurposing targets for COPD. / Pharmaceutical Sciences