Respiratory Symptoms in the Elderly and Their Clinical Significance in the Recognition of Asthma
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UNIVERSITY OF SOUTHAMPTON RESPIRATORY SYMPTOMS IN THE ELDERLY AND THEIR CLINICAL SIGNIFICANCE IN THE RECOGNITION OF ASTHMA A thesis submitted for the degree of Doctor of Medicine JOHN ROBERT HORSLEY FACULTY OF MEDICINE 1990 © UNIVERSITY OF SOUTHAMPTON ABSTRACT FACULTY OF MEDICINE GERIATRIC MEDICINE Doctor of Medicine RESPIRATORY SYMPTOMS IN THE ELDERLY AND THEIR CLINICAL SIGNIFICANCE IN THE RECOGNITION OF ASTHMA by John Robert Horsley This study was carried out to estimate the prevalence of respiratory symp- toms amongst the elderly in the community and relate symptoms to objective lung function measurements, including bronchial hyperreactivity. A respir- atory symptoms questionnaire was sent to 2011 subjects (957 male) drawn by age-stratified random sampling from the age-sex registers of 4 group practices in Lymington, Sway and Brockenhurst. All were age >65 yrs (mean 77 ± 8 yrs; oldest 102 yrs) representing a 1 ;3.3 sample. 1803 (90%) replied, 1665 from the first mailing and a further 138 after a reminder (96% response excluding 136 who had died or moved). The accuracy of replies was verified for a randomly selected 20%, either by formal interview or telephone. Only 14% were current smokers. Morning chest tightness was experienced by 203 (11.3%), lasting > 1 hour in 44; 131 (7.3%) had episodes of nocturnal breathlessness; 437 (24.2%) experienced occasional wheezing. Only 296 (16.4%) had chronic bronchitis and 151 (8.4%) gave a history of asthma, of whom half (76) had active asthma. 489 (27.1%) had seen their doctor with chest symptoms within the preceding 2 years. Sub-dividing by symptoms: I No respiratory symptoms 715 (40%) II Exertional dyspnoea only 185 (10%) III Wheeze, cough or mild chest tightness 289 (16%) IV Symptoms of bronchial irritability 519 (29%) V Unclassified (incomplete questionnaires) 95 (5%) A random sample from each of groups I-IV was invited for examination, spirometry and methacholine inhalation bronchial challenge. The dose of methacholine producing a 20% fall in FEVi was termed the 'PD20'. Of 180 attending, 20 were excluded (FEVi <1.0/ or spirometry not reproducible); 90 had a negative challenge and 69 (38%) had a positive challenge at or below a cumulative dose of 6.13//mol methacholine, 19 (12% of total) of these having highly reactive airways (PD20 < 1.0//mol). Subjects with low baseline FEVi (1.0 - 1.5 / ) were more likely to have a positive challenge result, and significantly more of these had highly reactive airways than to subjects with FEVi >1.5/. The presence of respiratory symptoms (groups III, IV) correlated with increased airway reactivity, but the clear separation of subjects (group IV) with the bronchial irritability syndrome symptoms reported by Mortagy et al (1986) was not observed in the elderly. This has important implications for the assessment and treatment of elderly patients with respiratory symptoms, since bronchial hyperreactivity, which is closely associated with clinical asthma, is far more common amongst the elderly than previously recognised. TABLE OF CONTENTS PAGE Abstract (H) List of tables (vii) List of illustrations (X) List of abbreviations (xti) Acknowledgements INTRODUCTION 1 PART 1 - LITERATURE SURVEY Chapter 1 ; Pathophysiology of the ageing lung 1.1 Introduction 7 1.2 Biochemical and structural changes in the ageing lung g 1.3 Changes within the chest wall 1 -j 1.4 Functional assessment ^4 1.5 Limitations of predictive "normal" values 15 1.6 Changes in lung volume -j 5 .1 Static lung volumes -jg .2 Dynamic tests of lung function 13 Chapter 2 : Various respiratory problems in relation to ageing 2.1 Response to infection and anaesthesia 23 2.2 Breathlessness 26 2.3 Smoking and chronic lung disease 29 Chapter 3: Asthma 3.1 Introduction 33 3.2 Definition of asthma 34 3.3 The prevalence of asthma 36 3.4 Asthma in the elderly 39 3.5 Asthma mortality 40 3.6 Treating asthma in the elderly 42 Chapter 4 : Bronchial hyperreactivity - clinical significance and assessment 4.1 Introduction and historical review 44 4.2 Nonspecific bronchial reactivity 46 4.3 Epidemiologic studies of bronchial hyperreactivity 50 4.4 Assessment of bronchial reactivity 57 .1 Techniques 57 .2 Agents used in challenge studies 59 .3 Factors affecting response to challenge studies 59 (iii) PART 2 - EXPERIMENTAL 61 Chapter 5 : Population demography and postal survey 5.1 Introduction 62 5.2 Subjects and methods 64 .1 General organisation 64 .2 Determination of sample size 64 .3 Sample selection 64 .4 Postal survey 65 .5 Data analysis 66 5.3 Results 66 .1 Population demography 66 .2 Response to postal questionnaire 68 5.4 Discussion 70 5.5 Conclusions 73 Chapter 6 : The prevalence of respiratory symptoms amongst the New Forest elderly - Results of the postal questionnaire 6.1 Introduction 74 6.2 Method; data analysis 74 6.3 Results 75 .1 Completeness and verification of questionnaires 75 .2 Smoking status 75 .3 Medical attention 76 .4 Breathlessness 76 .5 Nocturnal breathlessness 76 .6 Morning chest tightness 77 .7 Wheezing 77 .8 Productive cough 77 .9 Asthma 78 .10 Effect of ainway irritants 78 .11 Symptom subgroups 81 6.4 Discussion 83 6.5 Conclusions 85 Chapter 7 : Subgroup analysis - Selection and physical examination findings 7.1 Introduction 86 7.2 Subjects and method 88 7.3 Results 88 .1 Response to letter 88 .2 Interview 89 .3 Physical examination 91 7.4 Discussion 92 7.5 Conclusions 93 (iv) Chapter 8: Subgroup analysis - Pulmonary function studies 8.1 Introduction 94 8.2 Subjects and method 94 8.3 Results 95 .1 Bronchodilator responsiveness of 95 those excluded from challenge studies .2 Initial spirometry for groups 1-4 95 prior to challenge studies 8.4 Discussion 96 8.5 Conclusions 98 Chapter 9: Subgroup analysis - Measurement of bronchial reactivity to inhaled methacholine 9.1 Introduction 99 9.2 Subjects and method 100 .1 Estimation of nebuliser output 100 .2 Preparation of methacholine solutions 101 .3 Challenge procedure 101 .4 General precautions and reasons for 102 exclusion from challenge studies .5 Consent and discussion of results 103 9.3 Results 103 .1 Nebuliser output 103 .2 Subjects excluded from challenge studies 104 .3 Challenge studies 104 .4 Relationship between low FEVi and airway reactivity 107 .5 Correlation between changes in FEVi and PEFR 107 following challenge testing .6 Airway reactivity related to smoking history 108 .7 Airway reactivity related to respiratory symptoms 108 9.4 Discussion 110 9.5 Conclusions 113 Chapter 10: General discussion 10.1 Assessment of the elderly 114 10.2 A respiratory symptoms survey amongst the elderly 116 10.3 Was further interview and examination necessary? 118 10.4 Pulmonary function assessment 118 10.5 Bronchial hyperreactivity 119 (v) Chapter 11: Summary and indications for further research 11.1 Indications for the present study 124 11.2 Study design 124 11.3 Response to postal questionnaire 125 11.4 Respiratory symptoms 125 11.5 Definition of subgroups for further study 126 11.6 Spirometry 127 11.7 Indications for exclusion from challenge studies 128 11.8 Prevalence of bronchial hyperreactivity 128 11.9 Conclusions 129 11.10 Indications for further study 129 REFERENCES 131 APPENDICES A Questionnaires: 1 Postal questionnaire 156 2 Supplementary questonnaire 158 B Correspondence: 1 Initial letter to subjects 162 2 Reminder letter 163 3 Letter to Health Visitors 164 4 Incomplete forms letter 165 5 Further study letter 166 6 Physical examination data recording form 167 7 Consent form for methacholine challenge 169 8 Methacholine challenge doseage schedule 170 (full and abbreviated challenge protocols) 9 Results summary for general practitioner 171 C Supplementary tables (see list of tables) 172 (vi) LIST OF TABLES TABLE PAGE 1 Factors adversly affecting survival from pneumonia 25 in the elderly. 2 Factors associated with shortness of breath on 27 exertion in elderly subjects. 3 Relationship between FEVi and respiratory symptoms 32 in 450 elderly people (age range 62-90). 4 Various estimates of asthma prevalence in different 38 communities. 5 Relationship of bronchodilator responsiveness to 40 respiratory symptoms in 195 randomly selected elderly patients. 6 Factors affecting nonspecific bronchial reactivity. 49 7 Summary of published data regarding prevalence of 54 bronchial hyperreactivity. 8 Factors affecting the deposition of aerosols within 61 the respiratory tract during bronchial inhalation challenge studies. 9 Total number of patients listed with 4 New Forest 67 group practices; age-sex register compared with PRC. figures. 10 Parish population estimates in study area. 68 11 Proportionate sampling rates from age-sex register 68 for different age-bands according to age of subject 12 Percentage response to postal questionnaire for 69 different age-groups. 13 Comparison of the place of permanent residence 70 within different age-groups for 1803 respondents to the postal questionnaire. 14 Smoking status by age-group of 1803 respondents to 76 questionnaire. (vii) 15 Subdivision of 1803 respondents to the postal 81 questionnaire according to respiratory symptoms. 16 Prevalence of previously diagnosed asthma within 82 symptom subgroups. 17 Prevalence of respiratory symptoms in a general 87 population sample drawn from the Southampton electoral register compared to a sample from the Lymington and New Forest elderly population. 18 Response to written invitation to attend for 89 further study. 19 Number of medications being taken by 180 subjects, 90 principal diagnosis and smoking history within groups according to respiratory symptoms. 20 Results of physical (chest) examination and basic 91 anthropomorphic data. 21 Initial spirometry 96 22 Mean output from 10 DeVilbiss 40 nebulisers on two 103 separate days. 23 Outcome of challenge studies in 160 subjects, all 105 aged 65 years, divided according to pre-challenge respiratory symptoms. 24 Relationship between FEVi and level of bronchial 107 reactivity to inhaled methacholine.