Yale University EliScholar – A Digital Platform for Scholarly Publishing at Yale Yale School of Medicine Physician Associate Program Theses School of Medicine 6-19-2020 A Structured Airway Clearance and Exercise Program to Improve Clinical Outcomes in Cystic Fibrosis Rachel Rose Yale Physician Associate Program, [email protected] Follow this and additional works at: https://elischolar.library.yale.edu/ysmpa_theses Recommended Citation Rose, Rachel, "A Structured Airway Clearance and Exercise Program to Improve Clinical Outcomes in Cystic Fibrosis" (2020). Yale School of Medicine Physician Associate Program Theses. 29. https://elischolar.library.yale.edu/ysmpa_theses/29 This Open Access Thesis is brought to you for free and open access by the School of Medicine at EliScholar – A Digital Platform for Scholarly Publishing at Yale. 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A STRUCTURED AIRWAY CLEARANCE AND EXERCISE PROGRAM TO IMPROVE CLINICAL OUTCOMES IN CYSTIC FIBROSIS A Thesis Presented to The Faculty of the School of Medicine Yale University In Candidacy for the Degree of Master of Medical Science June 2020 Rachel Rose, PA-SII Clemente Britto-Leon, MD Class of 2020 Assistant Professor of Medicine Yale Physician Associate Yale School of Medicine Program Table of Contents LIST OF TABLES ............................................................................................................. iv LIST OF FIGURES ........................................................................................................... iv ABSTRACT ........................................................................................................................ v CHAPTER 1 – INTRODUCTION ..................................................................................... 1 1.1 BACKGROUND ............................................................................................................ 1 1.2 STATEMENT OF THE PROBLEM ................................................................................... 3 1.3 GOALS AND OBJECTIVES ............................................................................................ 3 1.4 HYPOTHESIS ............................................................................................................... 4 1.5 DEFINITIONS .............................................................................................................. 4 1.6 REFERENCES .............................................................................................................. 5 CHAPTER 2 – REVIEW OF THE LITERATURE ........................................................... 7 2.1 INTRODUCTION........................................................................................................... 7 2.2 CYSTIC FIBROSIS AND AIRWAY CLEARANCE THERAPY ............................................. 7 2.3 EXERCISE ................................................................................................................. 10 2.3.1 Exercise Benefits in Healthy Adults ................................................................. 10 2.3.2 Exercise and Cystic Fibrosis ........................................................................... 11 2.3.3 Exercise and Lung Function ............................................................................ 12 2.3.4 Exercise and Sputum Expectoration ................................................................ 15 2.3.5 Exercise and Quality of Life ............................................................................ 16 2.4 AIRWAY CLEARANCE THERAPY VS. EXERCISE ......................................................... 18 2.5 COMBINED EXERCISE AND AIRWAY CLEARANCE THERAPY..................................... 19 2.6 FEV1 AND SECONDARY OUTCOMES (EXACERBATIONS AND QUALITY OF LIFE) ...... 25 2.7 ADHERENCE TO THERAPY ........................................................................................ 26 2.8 POSSIBLE CONFOUNDERS ......................................................................................... 29 2.9 REVIEW OF RELEVANT METHODOLOGY ................................................................... 32 2.9.1 Measuring FEV1............................................................................................... 32 2.9.2 Survey to Measure Quality of Life ................................................................... 34 2.9.3 Inclusion and Exclusion Criteria ..................................................................... 34 2.9.4 Recruitment ...................................................................................................... 35 2.9.5 Sample Size ...................................................................................................... 36 2.9.6 Intervention ...................................................................................................... 36 2.9.7 Adverse Events ................................................................................................. 38 2.10 CONCLUSION .......................................................................................................... 38 2.11 REFERENCES .......................................................................................................... 40 CHAPTER 3 – STUDY METHODS ................................................................................ 44 3.1 STUDY DESIGN ......................................................................................................... 44 3.2 STUDY POPULATION AND SAMPLING ....................................................................... 44 3.3 INCLUSION ............................................................................................................... 45 3.4 EXCLUSION .............................................................................................................. 45 3.5 SUBJECT PROTECTION AND CONFIDENTIALITY ........................................................ 46 3.6 RECRUITMENT .......................................................................................................... 46 3.7 STUDY VARIABLES AND MEASURES ........................................................................ 47 3.8 METHODOLOGY CONSIDERATIONS ........................................................................... 48 ii 3.8.1 Experimental Protocol ..................................................................................... 48 3.8.2 Blinding of Intervention ................................................................................... 49 3.8.3 Blinding of Outcome ........................................................................................ 50 3.8.4 Assignment of Intervention .............................................................................. 50 3.8.5 Adherence ........................................................................................................ 50 3.8.6 Monitoring of Adverse Events .......................................................................... 50 3.9 DATA COLLECTION .................................................................................................. 51 3.10 SAMPLE SIZE CALCULATION .................................................................................. 51 3.11 ANALYSIS .............................................................................................................. 52 3.12 TIMELINE AND RESOURCES .................................................................................... 53 3.13 REFERENCES .......................................................................................................... 54 CHAPTER 4 – CONCLUSION ....................................................................................... 55 4.1 ADVANTAGES AND DISADVANTAGES ....................................................................... 55 4.2 CLINICAL AND PUBLIC HEALTH SIGNIFICANCE ........................................................ 56 APPENDICES .................................................................................................................. 58 APPENDIX A. SAMPLE CONSENT FORM .......................................................................... 58 APPENDIX B. SAMPLE RECRUITMENT FLYER ................................................................. 63 APPENDIX C. SAMPLE CFQ-R SURVEY .......................................................................... 64 APPENDIX D. LIST OF EXERCISE OPTIONS ...................................................................... 68 APPENDIX E: SAMPLE EXERCISE AND ACT DAILY LOG ................................................ 69 APPENDIX F. CALCULATIONS FOR TARGET HEART RATE .............................................. 70 APPENDIX G. SAMPLE SIZE CALCULATION .................................................................... 71 COMPLETE BIBLIOGRAPHY ....................................................................................... 73 iii List of Tables Figure 1: Proposed Study Design .................................................................................... 44 Figure 2. Sample Weekly Schedule of ACT and Exercise .............................................. 49 Figure 3. Proposed Study Phases ..................................................................................... 53 List of Figures Table 1. Primary and Secondary Outcomes ....................................................................