Phenotyping of obstructive airways disease

<p>Background Asthma and Chronic Obstructive Pulmonary Disease (COPD) are heterogeneous disorders which may be made up of different sub-types, or phenotypes, of airflow obstruction with distinct clinical characteristics. To facilitate personalised treatment the different phenotypes and their response to treatment must be clearly defined and sound diagnostic rules developed. In this thesis I explore the evidence supporting candidate phenotypes and report the results of my research, known as the New Zealand Respiratory Health Survey (NZRHS). The NZRHS was designed to determine candidate phenotypes, compare these phenotypes to those previously described, characterize their response to inhaled medication, and develop a method for allocating patients to the most appropriate phenotype. Research Aims -To explore clinical phenotypes of chronic airways disease by cluster analysis. -To examine if phenotypes identified by a previous cluster analysis exist in the independent NZRHS sample. -To compare the response to a short-acting beta-agonist inhaler between phenotype groups. -To compare the response to a short-acting muscarinic antagonist inhaler between phenotype groups. -To compare the response to an inhaled corticosteroid between phenotype groups. -To generate allocation rules and determine their predictive value for the different disorders of airways disease. Conclusions This research has identified phenotypes of airways disease that differ significantly in their clinical and pathophysiological characteristics. Evidence is presented to support the existence of the asthma/COPD overlap and obesity/co-morbid phenotypes and provide data of their responsiveness to inhaled corticosteroid, beta agonist and anti-muscarinic treatments, which may guide future management of patients with these phenotypes of obstructive airways disease.</p>

Phenotyping of obstructive airways disease

<p>Background Asthma and Chronic Obstructive Pulmonary Disease (COPD) are heterogeneous disorders which may be made up of different sub-types, or phenotypes, of airflow obstruction with distinct clinical characteristics. To facilitate personalised treatment the different phenotypes and their response to treatment must be clearly defined and sound diagnostic rules developed. In this thesis I explore the evidence supporting candidate phenotypes and report the results of my research, known as the New Zealand Respiratory Health Survey (NZRHS). The NZRHS was designed to determine candidate phenotypes, compare these phenotypes to those previously described, characterize their response to inhaled medication, and develop a method for allocating patients to the most appropriate phenotype. Research Aims -To explore clinical phenotypes of chronic airways disease by cluster analysis. -To examine if phenotypes identified by a previous cluster analysis exist in the independent NZRHS sample. -To compare the response to a short-acting beta-agonist inhaler between phenotype groups. -To compare the response to a short-acting muscarinic antagonist inhaler between phenotype groups. -To compare the response to an inhaled corticosteroid between phenotype groups. -To generate allocation rules and determine their predictive value for the different disorders of airways disease. Conclusions This research has identified phenotypes of airways disease that differ significantly in their clinical and pathophysiological characteristics. Evidence is presented to support the existence of the asthma/COPD overlap and obesity/co-morbid phenotypes and provide data of their responsiveness to inhaled corticosteroid, beta agonist and anti-muscarinic treatments, which may guide future management of patients with these phenotypes of obstructive airways disease.</p>

Dietary phenotype and advanced glycation end-products predict WTC-obstructive airways disease: a longitudinal observational study

Background Diet is a modifier of metabolic syndrome which in turn is associated with World Trade Center obstructive airways disease (WTC-OAD). We have designed this study to (1) assess the dietary phenotype (food types, physical activity, and dietary habits) of the Fire Department of New York (FDNY) WTC-Health Program (WTC-HP) cohort and (2) quantify the association of dietary quality and its advanced glycation end product (AGE) content with the development of WTC-OAD. Methods WTC-OAD, defined as developing WTC-Lung Injury (WTC-LI; FEV1 < LLN) and/or airway hyperreactivity (AHR; positive methacholine and/or positive bronchodilator response). Rapid Eating and Activity Assessment for Participants-Short Version (REAP-S) deployed on 3/1/2018 in the WTC-HP annual monitoring assessment. Clinical and REAP-S data of consented subjects was extracted (7/17/2019). Diet quality [low-(15–19), moderate-(20–29), and high-(30–39)] and AGE content per REAP-S questionnaire were assessed for association with WTC-OAD. Regression models adjusted for smoking, hyperglycemia, hypertension, age on 9/11, WTC-exposure, BMI, and job description. Results N = 9508 completed the annual questionnaire, while N = 4015 completed REAP-S and had spirometry. WTC-OAD developed in N = 921, while N = 3094 never developed WTC-OAD. Low- and moderate-dietary quality, eating more (processed meats, fried foods, sugary drinks), fewer (vegetables, whole-grains),and having a diet abundant in AGEs were significantly associated with WTC-OAD. Smoking was not a significant risk factor of WTC-OAD. Conclusions REAP-S was successfully implemented in the FDNY WTC-HP monitoring questionnaire and produced valuable dietary phenotyping. Our observational study has identified low dietary quality and AGE abundant dietary habits as risk factors for pulmonary disease in the context of WTC-exposure. Dietary phenotyping, not only focuses our metabolomic/biomarker profiling but also further informs future dietary interventions that may positively impact particulate matter associated lung disease.

Dietary Phenotype and Advanced Glycation End-Products Predict WTC-Obstructive Airways Disease: a Longitudinal Observational Study

BACKGROUND. Diet is a modifier of metabolic syndrome which in turn is associated with World Trade Center Obstructive Airways Disease(WTC-OAD). We have designed this study to 1.assess the dietary phenotype(food types, physical activity, and dietary habits) of the Fire Department of New York(FDNY) WTC-Health Program(WTC-HP) cohort and 2.quantify the association of dietary quality and its advanced glycation end product(AGE) content with the development of WTC-OAD.METHODS. WTC-OAD, defined as developing WTC-Lung Injury(WTC-LI;FEV1<LLN) and/or airway hyperreactivity(AHR;positive methacholine and/or positive bronchodilator response). Rapid Eating and Activity Assessment for Participants-Short Version(REAP-S) deployed on 3/1/2018 in the WTC-HP annual monitoring assessment. Clinical and REAP-S data of consented subjects was extracted(7/17/2019). Diet quality[low-(15-19), moderate-(20-29), and high-(30-39)] and AGE content per REAP-S questionnaire were assessed for association with WTC-OAD. Regression models adjusted for smoking,hyperglycemia,hypertension,age on 9/11,WTC-exposure,BMI and job description. RESULTS. N=9,508 completed the annual questionnaire, while N=4,015 completed REAP-S and had spirometry. WTC-OAD developed in N=921, while N=3,094 never developed WTC-OAD. Low- and moderate-dietary quality, eating more (processed meats,fried foods,sugary drinks), fewer(vegetables,whole-grains),and having a diet abundant in AGEs were significantly associated with WTC-OAD. Smoking was not a significant risk factor of WTC-OAD. CONCLUSIONS. REAP-S was successfully implemented in the FDNY WTC-HP monitoring questionnaire and produced valuable dietary phenotyping. Our observational study has identified low dietary quality and AGE abundant dietary habits as risk factors for pulmonary disease in the context of WTC-exposure. Dietary phenotyping, not only focuses our metabolomic/biomarker profiling but also further informs future dietary interventions that may positively impact particulate matter associated lung disease.

Dietary Phenotype and Advanced Glycation End-Products Predict WTC-Obstructive Airways Disease: a Longitudinal Observational Study

BACKGROUND. Diet is a modifier of metabolic syndrome which in turn is associated with World Trade Center Obstructive Airways Disease(WTC-OAD). We have designed this study to 1.assess the dietary phenotype(food types, physical activity, and dietary habits) of the Fire Department of New York(FDNY) WTC-Health Program(WTC-HP) cohort and 2.quantify the association of dietary quality and its advanced glycation end product(AGE) content with the development of WTC-OAD.METHODS. WTC-OAD, defined as developing WTC-Lung Injury(WTC-LI;FEV1<LLN) and/or airway hyperreactivity(AHR;positive methacholine and/or positive bronchodilator response). Rapid Eating and Activity Assessment for Participants-Short Version(REAP-S) deployed on 3/1/2018 in the WTC-HP annual monitoring assessment. Clinical and REAP-S data of consented subjects was extracted(7/17/2019). Diet quality[low-(15-19), moderate-(20-29), and high-(30-39)] and AGE content per REAP-S questionnaire were assessed for association with WTC-OAD. Regression models adjusted for smoking,hyperglycemia,hypertension,age on 9/11,WTC-exposure,BMI and job description. RESULTS. N=9,508 completed the annual questionnaire, while N=4,015 completed REAP-S and had spirometry. WTC-OAD developed in N=921, while N=3,094 never developed WTC-OAD. Low- and moderate-dietary quality, eating more (processed meats,fried foods,sugary drinks), fewer(vegetables,whole-grains),and having a diet abundant in AGEs were significantly associated with WTC-OAD. Smoking was not a significant risk factor of WTC-OAD. CONCLUSIONS. REAP-S was successfully implemented in the FDNY WTC-HP monitoring questionnaire and produced valuable dietary phenotyping. Our observational study has identified low dietary quality and AGE abundant dietary habits as risk factors for pulmonary disease in the context of WTC-exposure. Dietary phenotyping, not only focuses our metabolomic/biomarker profiling but also further informs future dietary interventions that may positively impact particulate matter associated lung disease.