Stress and obstructive airway diseases association and the mediating role of neuropeptide y

STRESS AND OBSTRUCTIVE AIRWAY DISEASES: ASSOCIATION AND THE MEDIATING ROLE OF NEUROPEPTIDE Y LU YANXIA (MASTER OF EDUCATION) A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF PSYCHOLOGICAL MEDICINE NATIONAL UNIVERSITY OF SINGAPORE 2014 ACKNOWLEDGEMENT I would like to express my deepest gratitude first and foremost to Associate Professor Ng Tze Pin, for his constant encouragement and instructions in the past four years. As a knowledgeable and dedicated supervisor, he has walked me through all the stages of the research and study of this exciting and hard journey. It is impossible for me to complete this PhD thesis without his expertise, encouragement, and concrete support. I am also deeply indebted to my co-supervisors Doctor Roger Ho Chun Man, Professor Hugo PS Van Bever, and Associate Professor Wong Wai Shiu Fred for their full support and specific guidance. From them, I learnt a lot about psycho-neuro-immunology from the perspectives of multiple disciplines. I wish to give cordial thanks to all the team members of the Gerontology Research Programme (GRP, NUS), the staffs in Department of Psychological Medicine (PCM, NUS), for all your help, support, and instructions. I would express my special thanks to my beloved parents, my sisters, and my boyfriend for their loving considerations, great confidence in me, and continuous support through these years, especially during my low tide time. Finally, my thanks would go to National University of Singapore for awarding me the NUS Research Scholarship which makes all those research activities possible. I wish I will be able to contribute more to Singapore as well as the academic world when I continue my academic life in this promising country. I LIST OF PUBLICATIONS 1. Lu YX, Ho RC, Lim TK, Kuan WS, Goh DY, Mahadevan M, Sim TB, van Bever HP, Larbi A, Ng TP. Neuropeptide Y may mediate psychological stress and enhance Th2 inflammatory response in asthma. J Allergy Clin Immunol. 2015; in press. 2. Lu YX, Feng L, Feng L, Nyunt MS, Yap KB, Ng TP. Systemic inflammation, depression and obstructive pulmonary function: a population-based study. Respir Res. 2013;14:53. 3. Lu YX, Mak KK, van Bever HP, Ng TP, Mak A, Ho RC. Prevalence of anxiety and depressive symptoms in adolescents with asthma: a meta-analysis and meta-regression. Pediatr Allergy Immunol. 2012;23:707-15. 4. Lu YX, Ho RC, Lim TK, Kuan WS, Goh DY, Mahadevan M, Sim TB, Ng TP, van Bever HP. Psychiatric comorbidities in Asian adolescent asthma patients and the contributions of neuroticism and perceived stress. J Adolesc Health. 2014;14:1-9. 5. Lu YX, Feng L, Lim L, Ng TP. Asthma, life events and psychiatric disorders: a populationbased study. Soc Psychiatry Psychiatr Epidemiol. 2013;48:1273-82. 6. Lu YX, Nyunt MS, Gwee X, Feng L, Feng L, Kua EH, Kumar R, Ng TP. Life event stress and chronic obstructive pulmonary disease (COPD): associations with mental well-being and quality of life in a population-based study. BMJ Open. 2012;2. 7. Lu YX, Tang C, Liow CS, Ng WN, Ho SH, Ho RC. A regressional analysis of maladaptive rumination, illness perception and negative emotional outcomes in Asian patients suffering from depressive disorder. Asian J Psychiatr. 2014;12:69-76. 8. Lu YX, Ho RC, Lim TK, Kuan WS, Goh DY, Mahadevan M, Sim TB, van Bever HP, Larbi A, Ng TP. Obesity, inflammatory cytokines, adiponectin and neuropeptide Y: associations with asthma prevalence and Th2-cytokine (interleukin-4) marker of allergic airway inflammation. To be submitted. 9. Lu YX, Ho RC, Lim TK, Kuan WS, Goh DY, Mahadevan M, Sim TB, van Bever HP, Larbi A, Ng TP. Neuropeptide Y polymorphism and adiposity in asthma during a one-year prospective follow-up. To be submitted. II CONTENTS ACKNOWLEDGEMENT I LIST OF PUBLICATIONS II ABSTRACT IX LIST OF TABLES XIII LIST OF FIGURES XIV LIST OF ABBRIVIATIONS XV 1. INTRODUCTION 1.1 Obstructive airway disease and its burden to society 1.2 Psychiatric comorbidity in obstructive airway disease 1.3 Psychological stress and airway obstruction 1.4 Objectives of the current study 2. LITERATURE REVIEW 2.1 Psychological stress and airway obstruction 2.1.1 Psychological stress 2.1.2 Psychological stress and asthma exacerbation 2.1.3 Psychological stress and asthma onset III 10 2.1.4 Psychological stress and COPD 12 2.1.5 Underlying mechanism 12 2.2 Inter-individual variability of stress and asthma 14 2.2.1 Age characteristics of asthma 14 2.2.2 Inter-individual variability of stress 17 2.3 Neuropeptide Y and inter-individual variability in stress-asthma link 19 2.3.1 Structure and function of Neuropeptide Y 20 2.3.2 Neuropeptide Y and psychological stress 21 2.3.3 Neuropeptide Y and inter-individual variability of stress in asthma 22 24 3. METHODS 3.1 Study I: Prevalence of anxiety and depressive symptoms in adolescents with asthma: 24 a meta-analysis and meta-regression 3.1.1 Search strategy 24 3.1.2 Criteria for article selection 24 3.1.3 Data abstraction 25 3.1.4 Statistical analyses 25 3.2 Study II: Asthma control, perceived stress, and quality of life in adolescents with IV 26 asthma: a case-control study 3.2.1 Study design and participants 26 3.2.2 Asthma control and asthma quality of life 27 3.2.3 Depression and anxiety 28 3.2.4 Stressful life events and perceived stress 28 3.2.5 Socio-demographic data and self-rated health 29 3.2.6 Statistical analyses 30 3.3 Study III: Asthma, psychological stress and psychiatric morbidity: a population- 31 based study in adult Singaporeans 3.3.1 Study design and participants 31 3.3.2 Asthma and other chronic physical conditions 31 3.3.3 Psychiatric disorders 33 3.3.4 Stressful life events and quality of life 34 3.3.5 Statistical analyses 35 3.4 Study IV: The impact of stressful life events on quality of life in the elderly with 36 airway obstruction 3.4.1 Study design and participants 36 V 3.4.2 Airway obstruction 37 3.4.3 Stressful life events and depressive symptoms 37 3.4.4 Cognitive function 38 3.4.5 Physical and mental functioning 38 3.4.6 Statistical analyses 39 3.5 Study V: Stress, neuropeptide Y, and young adult asthma: a follow-up study 40 3.5.1 Study design and participants 40 3.5.2 Spirometric test 41 3.5.3 Questionnaire administration 41 3.5.4 Enzyme-linked immunosorbent assay (ELISA) and Multiplex analysis 43 3.5.5 Socio-demographic data and clinical profile 44 3.5.6 Statistical analyses 44 46 4. RESULTS 4.1 Study I: Prevalence of anxiety and depressive symptoms in adolescents with asthma: 46 a meta-analysis and meta-regression 4.1.1 Aggregate prevalence and pooled odds ratio of depressive symptoms in adolescents with asthma versus the healthy controls VI 46 4.1.2 Aggregate prevalence and pooled odds ratio of anxiety symptoms in 49 adolescents with asthma versus the healthy controls 4.2 Study II: Asthma control, perceived stress, and quality of life in adolescents with 53 asthma: a case-control study 4.2.1 Demographics 53 4.2.2 Asthma control 53 4.2.3 Psychiatric comorbidities 53 4.2.4 Contribution of perceived stress to psychiatric comorbidity 54 4.3 Study III: Asthma, psychological stress and psychiatric comorbidity: a population- 63 based study in adult Singaporeans 4.3.1 Study participants 63 4.3.2 Comorbidity of psychiatric disorders with asthma and other chronic physical 63 conditions 4.3.3 Stressful life events as a mediating factor for psychiatric comorbidity 67 4.3.4 Relative contribution of stressful life events and concurrent psychiatric 68 disorders to impaired quality of life 4.4 Study IV: The impact of stressful life events on quality of life in the elderly with 72 airway obstruction 4.5 Study V: Stress, neuropeptide Y, and young adult asthma: a follow-up study VII 77 84 5. DISCUSSION 5.1 Study I: Prevalence of anxiety and depressive symptoms in adolescents with asthma: 84 a meta-analysis and meta-regression 5.1.1 Higher prevalence of depressive symptoms among adolescents with asthma 84 5.1.2 Higher prevalence of anxiety symptoms among adolescents with asthma 86 5.2 Study II: Asthma control, perceived stress, and quality of life in adolescents with 88 asthma: a case-control study 5.3 Study III: Asthma, psychological stress and psychiatric comorbidity: a population- 91 based study in adult Singaporeans 5.4 Study IV: The impact of stressful life events on quality of life in the elderly with 94 airway obstruction 5.5 Study V: Stress, neuropeptide Y, and young adult asthma: a follow-up study 98 6. SUMMARY AND CONCLUSION 104 7. REFERENCES 108 APPENDIX 122 VIII D A D A D A great deal of the time A lot of the time From time to time, but not too often Only occasionally I feel cheerful: Not at all Not often Sometimes Most of the time I can sit at ease and feel relaxed: Definitely Usually Not Often Not at all I feel as if I am slowed down: Nearly all the time Very often Sometimes Not at all I get a sort of frightened feeling like 'butterflies' in the stomach: Not at all Occasionally Quite Often Very Often I have lost interest in my appearance: 127 A D A D Definitely I don't take as much care as should I may not take quite as much care I take just as much care as ever I feel restless as I have to be on the move: Very much indeed Quite a lot Not very much Not at all I look forward with enjoyment to things: As much as I ever did Rather less than I used to Definitely less than I used to Hardly at all I get sudden feelings of panic: Very often indeed Quite often Not very often Not at all I can enjoy a good book or radio or TV program: Often Sometimes Not often Very seldom 128 The Holmes-Rahe Social Readjustment Ratings Scale (for children) Please put a circle around the word that happened to you during the last year in the following list. Yes No 1.Getting married 2.Unwed pregnancy 3.Death of parent 4.Acquiring a visible deformity 5.Divorce of parents 6.Fathering an unwed pregnancy 7.Becoming involved with drugs or alcohol 8.Jail sentence of parent for over one year 9.Marital separation of parents 10.Death of a brother or sister 11.Change in acceptance by peers 12.Pregnancy of unwed sister 13.Discovery of being an adopted child 14.Marriage of parent to step-parent 15.Death of a close friend 16.Having a visible congenital deformity 17.Serious illness requiring hospitalization 18.Failure of a grade in school 19.Not making an extracurricular activity 20.Hospitalization of a parent 21.Jail sentence of parent for over 30 days 22.Breaking up with boyfriend or girlfriend 23.Beginning to date 129 24.Suspension from school 25.Birth of a brother or sister 26.Increase in arguments between parents 27.Loss of job by parent 28.Outstanding personal achievement 29.Change in parent's financial status 30.Accepted at a college of your choice 31.Being a senior in high school 32.Hospitalization of a sibling 33.Increased absence of parent from home 34.Brother or sister leaving home 35.Addition of third adult to family 36.Becommg a full fledged member of a church 37.Decrease in arguments between parents 38.Decrease in arguments with parents 39.Mother or father beginning work 130 The Holmes-Rahe Social Readjustment Ratings Scale Please put a circle around the word that happened to you during the last year in the following list. Yes No 1. Death of a Spouse 2. Divorce 3. Marital Separation 4. Imprisonment 5. Death of a Close Family Member 6. Personal Injury or Illness 7. Marriage 8. Dismissal from Work 9. Marital Reconciliation 10. Retirement 11. Change in Health of Family Member 12. Pregnancy 13. Sexual Difficulties 14. Gain a New Family Member 15. Business Readjustment 16. Change in Financial State 17. Change in Frequency of Arguments 18. Major Mortgage 19. Fore closure of Mortgage or Loan 20. Change in Responsibilities at Work 21. Child Leaving Home 22. Trouble with In-Laws 23. Outstanding Personal Achievement 131 24. Spouse Starts or Stop Work 25. Begin or End School 26. Change in Living Conditions 27. Revision of Personal Habits 28. Trouble with Boss 29. Change in Working Hours or Conditions 30. Change in Residence 31. Change in Schools 32. Change in Recreation 33. Change in Church Activities 34. Change in Social Activities 35. Minor Mortgage or Loan 36. Change in Sleeping Habits 37. Change in Number of Family Reunions 38. Change in Eating Habits 39. Vacation 40. Christmas 41. Minor Violation of Law 132 Perceived Stress Scale (PSS) These questions ask you about your feelings, thoughts and activities during the last month, including today. In the last month, how often have you: Never Almost Never Sometimes Fairly Often Very Often 1. Been upset because of something that happened unexpectedly? 2. Felt that you were unable to control important things in your life? 3. Felt nervous and "stressed"? 4. Felt confident about your ability to handle your personal problems? 5. Felt that things were going your way? 6. Found that you could not cope with all things you had to do? 7. Been able to control irritations in your life? 8. Felt that you were on top of things? 9. Been angered because of things that happened that were out of your control? 10. Felt difficulties were piling up so high that you could not overcome them? 133 Pediatric Asthma Quality of Life Questionnaire We want you to tell us how much you have been bothered doing these things during the last week because of your asthma. Circle in the box that best describes how bothered you have been. HOW BOTHERED HAVE YOU BEEN DURING THE LAST WEEK? Extremel Very Quite Somewh Bothere y Bothere Bothere at d A Bit Bothered d d Bothered 1.Playing at recess 2.Running 3.Sleeping 4.Coughing Hardly Bothere d Not Bothere d Activity Not Done 6 7 0 Hardly any of the Time None of Time IN GENERAL, HOW OFTEN DURING THE LAST WEEK DID YOU: All of Most Quit Some of Once the of the e the in a Time time Ofte Time While n 5. Feel FRUSTRATED because of your asthma? 6. Feel TIRED because of your asthma? 7. Feel WORRIED, CONCERNED OR TROUBLED because of your asthma? HOW BOTHERED HAVE YOU BEEN DURING THE LAST WEEK BY? Extremel Very Quite Somewh Bothere y Bothere Bothere at d a Bit Bothered d d Bothered 8. Asthma Attacks? IN GENERAL, HOW OFTEN DURING THE LAST WEEK DID YOU: All of Most of Quite Some of Once in the the Often the a While Time Time Time 9. Feel ANGRY because of your asthma? 134 Hardly Bothere d Not Bothere d Hardly Any of the Time None of Time HOW BOTHERED HAVE YOU BEEN DURING THE LAST WEEK BY? Extremel Very Quite Somewh Bothere y Bothere Bothere at da Bit Bothered d d Bothered 10. Wheezing IN GENERAL, HOW OFTEN DURING THE LAST WEEK DID YOU: All of Most of Quit Some of the the e the Time Time Ofte Time n 11. Feel IRRITABLE / Grumpy because of your asthma? Hardly Any of the Time None of Time Hardly Bothere d Not Bothere d Once in a While Hardly Any of the Time None of Time Hardly Any of the Time None of Time Once in a While Hardly Any of the Time None of Time HOW BOTHERED HAVE YOU BEEN DURING THE LAST WEEK DID YOU: All of the Most of Quit Some of Once Time the Time e the in a Ofte Time While n 14. Shortness of breath IN GENERAL, HOW OFTEN DURING THE LAST WEEK DID YOU: All of Most of Quit Some of the the e the Time Time Ofte Time n 15. Feel FRUSTRATED because you couldn’t KEEP UP with others? 16. WAKE UP during the NIGHT because of your asthma? 135 Not Bothere d Once in a While HOW BOTHERED HAVE YOU BEEN DURING THE LAST WEEK BY? Extremel Very Quite Somewh Bothere y Bothere Bothere at d a Bit Bothered d d Bothered 12. Tightness in your chest IN GENERAL, HOW OFTEN DURING THE LAST WEEK DID YOU: All of Most of Quit Some of the the e the Time Time Ofte Time n 13. Feel different or left out because of your asthma? Hardly Bothere d 17. Feel UNCOMFORTABLE because of your asthma? 18. Feel OUT OF BREATH because of your asthma? 19. Feel you COULDN’T KEEP UP WITH OTHERS because of your asthma? 20. Have TROUBLE SLEEPING at night because of your asthma? 21. Feel FRIGHTENED by an ASTHMA attack? THINK ABOUT ALL THE ACTIVITIES THAT YOU DID IN THE PAST WEEK: Extremel Very Quite Somewh Bothere Hardly y Bothere Bothere at d A bit Bothere Bothered d d Bothered d 22. How much were you bothered by your asthma during these activities? IN GENERAL, HOW OFTEN DURING THE LAST WEEK DID YOU: All of Most Quit Some of the of the e the Time time Ofte Time n 23. Have difficulty taking a DEEP BREATH? 136 Not Bothere d Once in a While Hardly any of the Time None of Time Asthma Quality of Life Questionnaire Tick activities in which you are limited by asthma during the last week from the following list. If you are limited in more than activities because of asthma, choose activities you are most bothered. 10 11 12 13 Bicycling Clearing snow off your car Dancing Doing home maintenance Doing housework Gardening Hurrying Jogging, excercising, or running Laughing Mopping or scrubbing the floor Mowing the lawn Playing with pets Playing sports 14 15 16 17 18 19 20 21 22 23 24 25 Shovelling snow Singing Doing regular social activities Having sexual intercourse Talking Running upstairs or uphill Vacuuming Visiting friends or relatives Going for a walk Walking upstairs or uphill Woodwork or carpentry Carrying out your activities at work Fill in the blanks of the following questions with the activities you chose above, then answer the questions by ticking the answer that suits you best: Totally Extrem Very Modera Some A little Not limited, ely limite te limitati limitati at all couln’t limited d limitati on on limite activity at on d all 1. Please indicate how much you have been limited by your asthma in ? 1. Please indicate how much you have been limited by your asthma in ? 3. Please indicate how much you have been limited by your asthma in ? 4. Please indicate how much you have been limited by your asthma in ? 5. Please indicate how much you have been limited by your asthma in ? 137 Tick the answer that best suits you for the following questions. 6. How much discomfort or distress have you felt over the last weeks as a result of chest tightness? 7. In general, how often during the last weeks have you felt concerned about having asthma? All of the Time A very great deal A great A good deal deal Most of the Time A moderate amount Som e Very little N o A good bit of the time Some of the time A little of the time Hardly Any of the time None of the time 8. How often during the past weeks did you feel short of breath as a result of your asthma? 9. How often during the past weeks did you experience asthma symptoms as a result of being exposed to cigarette smoke? 10. How often during the past weeks did you experience a wheeze in your chest? 11. How often during the past weeks did you feel you had to avoid a situation or environment because of cigarette smoke? A very great deal 12. How much discomfort or distress have you felt over the past two weeks as a result of coughing? A great A good deal deal 138 A moderate amount Som e Very little N o All of the Time Most of the Time A good bit of the time Some of the time A little of the time Hardly Any of the time None of the time 14. How often during the past weeks did you experience a feeling of chest heaviness? 15. How often during the past weeks did you feel concerned about the need to take medication for your asthma? 16. How often during the past weeks did you feel the need to clear your throat? 17. How often during the past weeks did you experience asthma symptoms as a result of being exposed to dust? All of the Time Most of the Time A good bit of the time Some of the time A little of the time Hardly Any of the time None of the time 13. How often during the past weeks did you feel frustrated as a result of your asthma? 18. How often during the past weeks did you experience difficulty breathing out as a result of your asthma? 19. How often during the past weeks did you feel you had to avoid a situation or environment because of dust? 20. How often during the past weeks did you wake up in the morning with asthma symptoms? 21. How often during the past weeks did you feel afraid of not having your asthma medication available? 139 22. How often during the past weeks were you bothered by heavy breathing? 23. How often during the past weeks did you experience asthma symptoms as a result of the weather or air pollution outside? 24. How often during the past weeks have you been woken at night by your asthma? 25. How often during the past weeks have you had to avoid or limit going outside because of the weather or air pollution? 26. How often during the past weeks did you experience asthma symptoms as a result of being exposed to strong smells or perfume? 27. How often during the past weeks did you feel afraid of getting out of breath? 28. How often during the past weeks did you feel you had to avoid a situation or environment because of strong smells or perfume? 29. How often during the past weeks has your asthma interfered with getting a good night's sleep? 30. How often during the past weeks have you had the feeling of fighting for air? 140 Severely limitedmost activities not done 31. Think of the overall range of activities that you would have liked to have done during the past weeks. How much has your range of activities been limited by your asthma? 32. Overall, among all the activities that you have done during the past weeks, how limited have you been by your asthma? Very limite d Moderately limitedseveral activities not done Slightl y limited Totally limited, couln’t activity at all Extrem ely limited Very limite d 141 Very slightly limited-very few activities not done Moderat e limitatio n Hardly limited at all Not limited at all-have done all activities that I wanted to Some limitatio n A little Not at limitatio all n limited NEO-FFI Personality Test Strongly Disagree Neutral Agree Strongly Disagree Agree 1. I am not a worrier. 2. I often feel inferior to others. 3. When I’m under a great deal of stress, sometimes I feel like I’m going to pieces. 4. I rarely feel lonely or blue. 5. I often feel tense and jittery. 6. Sometimes I feel completely worthless. 7. I rarely feel fearful or anxious. 8. I often get angry at the way people treat me. 9. Too often, when things go wrong, I get discouraged and feel like giving up. 10. I am seldom sad or depressed. 11. I often feel helpless and want someone else to solve my problems. 12. At times I have been so ashamed I just wanted to hide. 142 [...]... inability to work, unemployment, interpersonal problems, low self-esteem, financial loss, poor mental health, and reduction of social functioning and life satisfaction With increased understanding of the 3 neurobiology of stress and the pathophysiology of airway diseases, elucidating the role of psychological stress in the development and control of airway obstruction is now distinctly possible There... groups of an Asian population These studies would contribute to the understanding of the role of stress in obstructive airway diseases, and provide the rationale for identifying key vulnerability and resilience factors for psychiatric comorbidity and screening patients for psychological treatment Hopefully, the findings from this study may facilitate the design of future clinical trials and the establishment... about airway disease aetiology, prevention and treatment This thesis focused on aspects of the contribution of psychological stress to the psychiatric comorbidity of airway obstruction in different age groups including adolescent, adult and the elderly individuals, as well as the role of neuropeptide Y (NPY) in mediating the persistent effect of perceived stress on heightening T helper cell type (Th)2... stress- airway obstruction association and its health impact in different age groups of adolescent, adult and elderly individuals respectively Finally, Study V was conducted to investigate the role of NPY in mediating stressairway obstruction link We hypothesized that: 1 Obstructive airway diseases would be associated with a high prevalence of anxiety and depressive symptoms and impaired QoL 2 More stressful... 2 1.1 Obstructive airway disease and its burden to society Obstructive airway diseases such as asthma and COPD are a category of respiratory diseases characterized by airway obstruction It is generally distinguished by inflamed and easily collapsible airways, airflow obstruction, problems with exhaling and frequent physician and Emergency Medicine Department (EMD) visits and hospitalizations 2 Obstructive. .. airway diseases are not well elucidated Objective: This study aims to explore the stress- airway obstruction association in adolescent, adult and elderly individuals, and the underlying role of neuropeptide Y (NPY) through a cross-sectional clinical study, a clinical follow-up study and population-based studies Methods: A systematic meta-analysis and meta-regression was performed about the prevalence of. .. gap, the current study aimed to assess the contribution of stressful life events and perceived stress in the psychiatric comorbidity and quality of life of asthma and COPD in adolescent, adult and elderly individuals, as well as the role of NPY in explaining the underlying neuroendocrine mechanism of this relationship Accordingly, several 4 related but independent studies were conducted For ease of reference,... psychological stress to the association of psychological symptoms and obstructive airway diseases NPY may be a plausible XI neuroendocrine mediator for the persistent effect of perceived stress on heightening Th2 immune and inflammatory responses in asthma, and a candidate for early targeted interventions XII LIST OF TABLES Table 1 Study design and baseline characteristics of studies included in meta-analysis... cortisol and NPY, reflecting blunted adaptive responses to chronic stress 5 5 Higher levels of psychological stress (perceived stress) /biological stress (HPA index) may be associated with increased levels of interleukin (IL)-4, and this is likely to be mediated by the levels of NPY This series of studies investigated the relationship between stress and psychiatric comorbidity in obstructive airway diseases. .. background of increasing mental health problems call for research into the relationship between stress and obstructive airway diseases 1.2 Psychiatric comorbidity in obstructive airway disease 2 Among obstructive airway diseases, asthma has historically long been considered as a typical psychosomatic disorder 13 Asthma, along with other obstructive airway diseases, is associated with a high comorbidity with . STRESS AND OBSTRUCTIVE AIRWAY DISEASES: ASSOCIATION AND THE MEDIATING ROLE OF NEUROPEPTIDE Y LU YANXIA (MASTER OF EDUCATION) A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY. Conclusions: Results of the present thesis suggest the pivotal role of psychological stress to the association of psychological symptoms and obstructive airway diseases. NPY may be a plausible XII. Objective: This study aims to explore the stress- airway obstruction association in adolescent, adult and elderly individuals, and the underlying role of neuropeptide Y (NPY) through a cross-sectional