Pulmonary Function in Patients with Ankylosing Spondylitis

Pulmonary Function in Patients with Ankylosing Spondylitis A cross sectional controlled study Gunnhild Berdal Master Thesis Department of Health Scie...
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Pulmonary Function in Patients with Ankylosing Spondylitis A cross sectional controlled study Gunnhild Berdal

Master Thesis Department of Health Sciences Institute of Health and Society Faculty of Medicine UNIVERSITY OF OSLO 2011

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PULMONARY FUNCTION IN PATIENTS WITH ANKYLOSING SPONDYLITIS A CROSS SECTIONAL CONTROLLED STUDY

Gunnhild Berdal

Master Thesis

Department of Health Sciences Institute of Health and Society Faculty of Medicine

UNIVERSITY OF OSLO 2011

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© Gunnhild Berdal 2011 Pulmonary Function in Patients with Ankylosing Spondylitis Gunnhild Berdal http://www.duo.uio.no/ Trykk: Reprosentralen, Universitetet i Oslo

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Table of Contents TABLE OF CONTENTS ACKNOWLEDGEMENTS ABBREVIATIONS ABSTRACT SAMMENDRAG INTRODUCTION

1

Background ....................................................................................................................... 1 1.1

History .................................................................................................................. 1

1.1.2

Etiology ................................................................................................................ 3

1.1.3

Epidemiology ....................................................................................................... 3

1.1.4

Clinical features.................................................................................................... 5

1.1.5

Diagnosis and classification ................................................................................. 8

1.1.6

Disease course and prognosis ............................................................................. 10

1.1.7

Recommendations for the management of AS ................................................... 12

Pulmonary manifestations of AS ............................................................................... 14

1.2.1

Prevalence of pulmonary involvement ............................................................... 16

1.2.2

Evaluation of pulmonary disease ....................................................................... 18

1.2.3

Management of respiratory impairments ........................................................... 18

Aims of the study ............................................................................................................ 20 2.1

3

Ankylosing Spondylitis ............................................................................................... 1

1.1.1

1.2

2

V VII IX XI XIII XV

Reasearch questions ................................................................................................... 20

Materials and Methods .................................................................................................. 21 3.1

Study design .............................................................................................................. 21

3.2

Inclusion of patients and population controls ............................................................ 21

3.3

Participants ................................................................................................................ 23

3.4

Measurements in the survey ...................................................................................... 23

3.4.1

Socio-demographic and disease related variables .............................................. 23

3.4.2

Assessment of pulmonary function .................................................................... 23

3.4.3

Assessment of AS............................................................................................... 31

3.4.4

Assessment of aerobic capacity (VO2peak) .......................................................... 34

3.4.5

Assessment of physical activity ......................................................................... 34

3.5

Statistical analysis...................................................................................................... 35

3.6

Ethics ......................................................................................................................... 36 V

4

Paper ................................................................................................................................ 37

5

Extended results ............................................................................................................. 38 5.1

Bivariate associations between pulmonary function and clinical measures .............. 38

5.2

Smoking – pulmonary function and clinical measures in the AS patients ................ 41

5.3

Demographic features – gender comparisons ............................................................ 43

5.4

Pulmonary function – gender comparisons ............................................................... 45

5.5

Clinical features – gender comparisons ..................................................................... 48

6

General discussion .......................................................................................................... 51 6.1

6.1.1

Study samples ..................................................................................................... 51

6.1.2

The AS patients .................................................................................................. 52

6.1.3

The population controls ...................................................................................... 53

6.1.4

Study design ....................................................................................................... 54

6.1.5

Methods of data collection ................................................................................. 54

6.1.6

Statistical issues.................................................................................................. 60

6.2

7

Methodological aspects ............................................................................................. 51

Extended results ......................................................................................................... 62

6.2.1

Pulmonary function and clinical findings .......................................................... 62

6.2.2

Smoking ............................................................................................................. 62

6.2.3

Physical capacity ................................................................................................ 63

6.2.4

Physical activity ................................................................................................. 64

6.2.5

Gender comparisons ........................................................................................... 65

Conclusion ....................................................................................................................... 69 7.1

Clinical implications and further research ................................................................. 70

8

Reference List ................................................................................................................. 71

9

Appendix ......................................................................................................................... 85

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Acknowledgements This thesis was written during 2010 - 2011 while I was a student at Department of Health Sciences, Faculty of Medicine, University of Oslo. I am very grateful to my employer Oslo University Hospital, Aker for granting me the financial support that made it possible for me to carry out the work on a full time basis. I also thank The Norwegian Fund for Postgraduate Education in Physiotherapy for grant to cover the direct expenses of the education. Hanne Dagfinrud (PT, PhD) at Diakonhjemmet Hospital was my main supervisor. I am profoundly grateful to her for kindly admitting me to the project, for encouraging support, and for down to earth, pragmatic guidance. Her experience, knowledge and highly competent advice provided a steady course for me through this project. Morten Mowe (MD, PhD) at Oslo University Hospital, Aker was my co-supervisor. I am indebted to him for invaluable general support. He read and commented on the whole manuscript, and gave important advice concerning the interpretation of the pulmonary function data. When I entered the project I found most things already prepared. I gratefully acknowledge the contributions of all who has partcipated in the study. The Norwegian Society for Rheumatism (NRF) and The Norwegian Fund for Postgraduate Education in Physiotherapy supported the data collection financially. Silje Halvorsen (PT, research fellow) and Camilla Fongen (PT, McS) played key roles in the data collection process and in organizing the logistics. I owe my very special thanks to them for their hospitality and generosity, for sharing their knowledge and experience with me, for productive conversations and statistical support, and for always and patiently responding to my numeric questions. Hanne, Morten and Silje all made substantial contributions to the article. Additionally, it is an honour to thank the dutch professor Desiree van der Heijde (MD) for her significant contribution to the article. I express my gratitude for the time and effort all my co-authors have invested in reading, discussing and counseling my work.

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I would also like to thank professor Nina Vøllestad for introducing me to the research group at Diakonhjemmet Hospital, and for her memorable lessons in statistics. It was a genuine pleasure to follow her classes. I am immensely grateful to Sveinung for his 24-7 IT support by visits, chats or phone, and for humerous replies and laughter in moments of despair. Most of all, I thank my family, in particular Geir, for giving me the time and space to complete my studies, and for patience and practical help throughout. His moral support and apparently endless belief in my abilities has been a major motivating force. Grandmother Jorunn made an enormous contribution as beloved baby-sitter for our baby girl during weekdays, as well as week-ends. I am really appreciative of all the help. Finally, I thank my children Sondre and Mathilde for bringing me happiness and joy every day.

Oslo, January 2011 Gunnhild Berdal

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Abbreviations AS – Ankylosing Spondylitis ASAS – Assessment of SpondyloArthritis international Society ASDAS - Ankylosing Spondylitis Disease Activity Score ATS – American Thoracic Society BASDAI – Bath Ankylosing Spondylitis Disease Activity Index BASFI - Bath Ankylosing Spondylitis Functional Index BAS-G - Bath Ankylosing Spondylitis Patient Global Assessment BASMI - The Bath Ankylosing Spondylitis Metrologi Index BMI – Body Mass Index CRP - C-Reactive Protein CT – Computed Tomography DMARD - Disease ModifyingAantirheumatic Drugs ECCS – European Community for Coal and Steel ESR – Eryhtrocyte Sedimentation Rate EULAR – European League Against Rheumatism FEV 1 - Forced Expiratory Volume in 1 second FEV 1 /FVC % – Absolute FEV 1 /FVC-ratio FRC – Functional Residual Capacity FVC – Forced Vital Capacity IX

HLA-B27 – Human Leukocyte Antigen- B27 IBD - Inflammatory Bowel Disease IBP – Inflammatory Back Pain ILD – Interstitial Lung Disease MET - Metabolic Equivalent of Task MRI – Magnetic Resonance Imaging NPV – Negative Predictive Value NSAID – Non-Steroid Anti Inflammatory Drugs NRS – Numeric Rating Scales OSAS – Obstructive sleep apnoea syndrome PEF – Peak Expiratory Flow PFT – Pulmonary Function Test PPV – Positive Predictive Value QOL – Quality Of Life RV – Residual Volume RA – Rheumatoid Atrhritis SES – Socio Economic Status SpA - SpondyloArthrides TLC - Total Lung Capacity TNF - Tumor necrosis factor VO 2peak – Peak Oxygen Uptake

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Abstract Background: Pulmonary involvement is a known manifestation in patients with ankylosing spondylitis (AS), emerging either as interstitial lung disease or in the form of restrictive pulmonary function. The reported prevalence of pulmonary involvement varies depending on the diagnostic methods applied. In some AS patients, inflammation in the thoracic vertebrae and costovertebral joints result in fusion, ossification and rigidity of the thorax. Hence, the associations between the typical clinical features and pulmonary function should be explored. Objectives: To compare pulmonary function in patients with AS and population controls, and to study associations between pulmonary function and disease related variables, cardiorespiratory fitness and demographic variables in patients with AS. Methods: In a cross-sectional controlled study, 147 patients with AS and 121 randomly selected population controls underwent comprehensive examinations including demographic variables, laboratory (C-reactive protein (mg/l), ESR) and clinical measures (disease activity (ASDAS, BASDAI), anthropometric (BASMI), cardio-respiratory fitness (VO2peak), patientreported physical function (BASFI) and pulmonary function test (PFT) (spirometry). Univariate ANCOVAs were performed to explore group differences in pulmonary function adjusting for relevant variables, and a multiple model was used to estimate the explanatory power of independent variables (demographic, disease related, VO2peak) on restrictive ventilatory impairment (FVC%). Results: AS patients showed significantly lower PFT values compared with the controls; forced vital capacity (FVC%) (97% vs 105%, p

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