Changes in Respiratory Symptoms Health-Related Quality of Life * and

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1 Changes in Respiratory Symptoms Health-Related Quality of Life * and Marianne Voll-Aanerud, Tomas M. L. Eagan, Tore Wentzel-Larsen, Amund Gulsvik and Per S. Bakke Chest 27;131; ; Prepublished online May 15, 27; DOI /chest The online version of this article, along with updated information and services can be found online on the World Wide Web at: Chest is the official journal of the American College of Chest Physicians. It has been published monthly since Copyright27by the American College of Chest Physicians, 33 Dundee Road, Northbrook, IL 662. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. ( ISSN:

2 CHEST Changes in Respiratory Symptoms and Health-Related Quality of Life* Marianne Voll-Aanerud, MD; Tomas M. L. Eagan, MD, PhD; Tore Wentzel-Larsen, MSc; Amund Gulsvik, MD, PhD; and Per S. Bakke, MD, PhD Original Research HEALTH-RELATED QUALITY OF LIFE Background: For a number of chronic diseases, health-related quality of life (HRQoL) has become an important outcome measure. Little data are available on how incidence, remission, or persistence of respiratory symptoms affect HRQoL. Methods: The Hordaland County Cohort Study was conducted between 1985 and 1997, and comprised 3,786 subjects, randomly selected, and aged 15 to 7 years in Respiratory symptoms were assessed both in 1985 and 1996/1997, and HRQoL was measured by the Short-Form 12 questionnaire in 1996/1997. Robust linear regression analysis was used to examine the relationship between changes in six respiratory symptoms and the physical component score (PCS) and mental component score (MCS). Results: Among subjects with incidence or persistence of any of the six examined respiratory symptoms, PCS and MCS were significantly lower than among subjects without symptoms. The PCS was more reduced than the MCS in symptomatic subjects; however, this trend was reduced after adjustment for the confounder s gender, age, educational level, body mass index, and smoking status. Dyspnea attacks and dyspnea grade 2 had the largest negative impact on both PCS and MCS. Conclusions: This is the first longitudinal population study to show the negative impact of incidence and persistence of respiratory symptoms on HRQoL. (CHEST 27; 131: ) Key words: health-related quality of life; respiratory symptoms; Short-Form-12 Abbreviations: BMI body mass index; EQ-5D EuroQol five dimension; HRQoL health-related quality of life; MCS mental component score; PCS physical component score; QoL quality of life; SF Short-Form For a number of chronic diseases, health-related quality of life (HRQoL) measured by standard questionnaires has become an important measure of the well-being of those affected. HRQoL is used to evaluate the magnitude of the impact of disease in observational studies, and increasingly as an outcome *From the Department of Thoracic Medicine (Drs. Voll-Aanerud and Eagan), Centre for Clinical Research (Mr. Wentzel-Larsen), and Institute of Medicine (Drs. Gulsvik and Bakke), Haukeland University Hospital, Bergen, Norway. None of the authors have any conflicts of interest related to the article or the research described. Manuscript received October 26, 26; revision accepted February 17, 26. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( org/misc/reprints.shtml). Correspondence to: Marianne Voll-Aanerud, MD, Department of Thoracic Medicine, Haukeland University Hospital, N-521 Bergen, Norway; Marianne.Aanerud@med.uib.no DOI: /chest measure in clinical trials. 1,2 Further, HRQoL can be important as a predictor of the use of health-care resources. 3 5 A disease often involves several different symptoms that may or may not have an impact on the patient well-being. Some symptoms may affect HRQoL more than others. Knowing the effect of individual symptoms on HRQoL may expand on the knowledge gained by studies of how disease affects HRQoL. Although several studies 6 8 have found that patients with asthma and COPD have lower HRQoL scores than healthy subjects, very few studies have examined the role of respiratory symptoms. Chronic cough, 9 dyspnea, 9 12 wheezing, 1 and morning or night awakenings 11 were associated with a worsened quality of life (QoL) in studies of patient populations with asthma. Only two population studies 13,14 have 189 Original Research

3 examined the impact of respiratory symptoms on HRQoL, both of which were cross-sectional in design. In South Wales, a random sample of 5 subjects aged 7 years was examined, and the presence of dyspnea was found to significantly impair Short-Form (SF)-36 questionnaire scores. 13 And, in a large patient register sample from England, the presence of wheeze, chest tightness, shortness of breath, and cough was associated with lower Euro- Qol five-dimension (EQ-5D) questionnaire scores. 14 Respiratory symptoms are often transient, with high remission and recurrence rates. Whether HRQoL varies with the incidence or remission of respiratory symptoms has not been previously examined. The aim of the current study was to examine how the incidence, remission, and persistence of six respiratory symptoms in a general population cohort related to HRQoL, measured by the Short-Form (SF)-12 questionnaire. Materials and Methods Study Population and Sample In 1985, 3,786 randomly selected subjects aged 15 to 7 years in the Norwegian city of Bergen and 11 surrounding municipalities were mailed a questionnaire regarding respiratory symptoms. After up to two reminder letters, 3,37 subjects (89%) responded to the questionnaire. 15 A follow-up was conducted in 1996/1997. Then, in addition to being sent a questionnaire on respiratory symptoms, the subjects were invited to a clinical examination. Between 1985 and 1996, 189 persons were deceased, leaving 3,181 eligible for the second phase. A total of 2,819 subjects (89%) returned the questionnaire on respiratory symptoms, and 2,45 subjects (76%) attended the clinical examination. 16 While attending the clinical examination, the subjects were invited to fill in the SF-12 QoL questionnaire. For calculation of the SF-12 scores, the questionnaire had to be fully completed, which was the case for 2,36 subjects. Informed consent was obtained from each participant prior to each survey, and both surveys were approved by the Regional Committee of Medical Research Ethics. Questionnaires The wording of the questions on respiratory symptoms is given in the Appendix. The questions regarding respiratory symptoms has been validated against lung function and bronchial reactivity, 17,18 and compared with the British Medical Research Council questionnaire on chronic bronchitis. 19 The SF-12 questionnaire is a 12-item, general, QoL questionnaire previously validated 2 and widely used in both general and diseased populations. 7,21 The SF-12 measures QoL in the physical component scale (PCS) and the mental component scale (MCS). 22 The scales range from to 7, and a higher score indicates a better HRQoL. Changes in smoking habits were defined by whether they were neversmokers, ex-smokers, or current smokers at baseline and at follow-up, and recoded into five categories: neversmoker to neversmoker, nonsmoker to current smoker, current smoker to current smoker, current smoker to ex-smoker, and ex-smoker to ex-smoker. The nonsmoker-to-current smoker category consisted of both neversmokers to current smokers, and ex-smokers to current smokers. Pack-years smoked was estimated by multiplying the duration of smoking in years by the number of cigarettes smoked per day and dividing the product by 2. Educational level was determined at follow-up and divided into three categories: up to 9 years of Table 1 Description of the Study Population by Gender Variables Women (n 1,193) Men (n 1,113) Mean age (SD), yr 5.6 (15.3) 48.8 (14.4) Education,* No. (%) Primary 233 (19.5) 183 (16.4) Secondary 682 (57.2) 641 (57.6) University 258 (21.6) 276 (24.8) Smoking history, No. (%) smoker to neversmoker 513 (45.3) 344 (32.) Ex-smoker to ex-smoker 14 (12.3) 216 (2.1) Nonsmoker to current smoker 59 (5.2) 55 (5.1) Current smoker to current smoker 39 (27.3) 331 (3.8) Current smoker to ex-smoker 112 (9.9) 129 (12.) Pack-years, No. (%) 513 (45.5) 344 (32.7) (27.3) 236 (22.4) (16.) 224 (21.3) (11.2) 248 (23.6) BMI, No. (%) Underweight 13 (1.1) 1 (.9) Normal weight 64 (54.2) 459 (41.4) Overweight 361 (3.5) 521 (46.9) Obese 168 (14.2) 12 (1.8) *Thirty-three subjects did not report an educational level. Ninety-eight subjects had inconsistent answers regarding smoking. One hundred ninety-eight subjects did not report pack-years. Fourteen subjects were not weighed. CHEST / 131 / 6/ JUNE,

4 schooling (primary), a degree requiring 12 years of schooling (secondary), and a higher degree of education (university). 23 Height and weight were measured during the clinical examination. Body mass index (BMI) was estimated by dividing the person s weight in kilograms by the square of his/her height in meters, and categorized into four groups according to the World Health Organization 24 : (1) underweight (BMI 18.5 kg/m 2 ); (2) normal weight (BMI, 18.5 to 24.9 kg/m 2 ); (3) overweight (BMI, 25 to 29.9 kg/m 2 ); and (4) obese (BMI 3 kg/m 2 ). 24 Statistical Analysis All statistical analysis was conducted using statistical software (Stata version 8.; StataCorp; College Station, TX). Categorical variables were described by frequency distributions and tables, and continuous variables were described by means and SDs in different subgroups of the sample (Tables 1, 2). Univariate relationships between SF-12 scores and the six respiratory symptoms (morning cough, chronic cough, phlegm cough, wheeze, dyspnea attacks, and dyspnea grade 2) were examined by the Kruskal-Wallis test. The multivariate relationship between the SF-12 scores and the explanatory variables were examined in robust linear regression models. In the models, gender, educational level, smoking habits, pack-years, BMI, all symptoms, and all the first-order interaction terms were included. Age was included as a continuous variable. Insignificant interactions terms Table 2 Description of the Symptoms Population by Gender* Respiratory Symptoms Women (n 1,193) Men (n 1,113) 2 Morning cough (67.1) 719 (64.6) Incidence 171 (14.3) 134 (12.) Remission 87 (7.3) 116 (1.4) Persistent 134 (11.2) 144 (12.9) Chronic cough (82.8) 96 (81.4) Incidence 11 (9.2) 86 (7.7) Remission 54 (4.5) 7 (6.3) Persistent 41 (3.5) 51 (4.6) Phlegm cough 832 (69.8) 679 (61.).1 Incidence 155 (13.) 155 (13.9) Remission 13 (8.6) 138 (12.4) Persistent 13 (8.6) 141 (12.7) Wheeze (68.5) 748 (67.2) Incidence 156 (13.1) 123 (11.1) Remission 98 (8.2) 114 (1.2) Persistent 122 (1.2) 128 (11.5) Dyspnea attacks (76.3) 92 (81.) Incidence 13 (1.9) 92 (8.3) Remission 78 (6.5) 67 (6.) Persistent 75 (6.3) 52 (4.7) Dyspnea grade (74.8) 937 (84.2) Incidence 162 (13.6) 86 (7.7) Remission 57 (4.7) 42 (3.8) Persistent 82 (6.9) 48 (4.3) *Data are presented as No. (%). For gender differences in distributions of symptom change. were omitted in the final model. To partially adjust for the skewed distributions of the SF-12 summary scores, robust variance estimation, which uses the Huber/White/sandwich estimator of variance in place of traditional variance estimation, was used. Due to the large number of significance tests performed, a nominal significance level of.1 was used. Results Characteristics of the study sample are presented in Table 1. A larger percentage of men had a university educational level. More women than men were neversmokers, and men tended to have higher smoking loads measured by pack-years (Table 1). The distribution of the changes in respiratory symptoms between genders is shown in Table 2. The distribution varied between genders for the symptoms phlegm cough and dyspnea grade 2. The occurrence of not having a symptom at either time point was higher for the cough symptoms among women, and for the dyspnea symptoms among men (Table 2). Both MCS and PCS had similar and skewed distribution patterns for all the symptoms. Figure 1 illustrates the distributions of PCS for dyspnea grade 2 and chronic cough. The univariate relationships between changes in respiratory symptoms and the PCS and MCS are presented in Table 3. All six symptoms affected both the PCS and the MCS in a nonrandom manner (p.1). For all symptoms, there was strikingly similar pattern; in which subjects never having a symptom have the highest component scores (both PCS and MCS), subjects with remission have the second highest component scores, subjects with incidence have the second lowest component scores, and subjects with persistent symptoms have the lowest component scores. Whereas the pattern was similar for both the PCS and MCS, the difference between the highest and lowest component scores was larger for the PCS (Table 3). The magnitude of the effect on PCS and MCS also differed between symptoms, with chronic cough, dyspnea attacks, and dyspnea grade 2 having the largest negative influence. The relationships between respiratory symptoms and QoL persisted in the multivariate analyses after adjustment for gender, age, educational level, smoking, BMI, and all other respiratory symptoms (Table 4). The symptoms with the largest effect on QoL were dyspnea attacks and dyspnea grade 2 in the multivariate analyses. However, the magnitude of the effect was reduced after adjustment for the confounders. After adjustments, chronic cough was not associated with reduced QoL. This was more pronounced for the PCS, so that the adjusted negative effect of incidence or persistence of attacks of dyspnea and dyspnea grade 2 was almost as large on the MCS as on the PCS (Table 4). Significant interactions were found between wheeze and age, wheeze and smoking, and dyspnea grade 2 and 1892 Original Research

5 without dyspnea grade two with incidence of dyspnea grade two with remission of dyspnea grade two without chronic cough with incidence of chronic cough with remission of chronic cough with persistence of dyspnea grade two with persistence of chronic cough Figure 1. Distributions of PCS for dyspnea grade 2 and chronic cough. age on the PCS. For the MCS, significant interactions were found between smoking and phlegm cough, age and dyspnea attacks, age and dyspnea grade 2, and pack-years smoked, and dyspnea grade 2. Significant interactions were included in the final multivariate models. Among the confounders most interactions were found with age, and those are presented in Table 5. In younger subjects, persistence of dyspnea grade 2 affected the MCS more than the PCS, compared to older subjects. Persistence of wheeze affected the PCS in younger subjects more than older subjects, whereas the opposite was true for dyspnea attacks and the MCS (Table 5). Discussion Among subjects with incidence or persistence of any of the six examined respiratory symptoms, the PCS and MCS were lower than among subjects without symptoms. In general, the PCS was more reduced than the MCS in symptomatic subjects; however, this trend was reduced after adjustment for the confounder s gender, age, educational level, and smoking status. Dyspnea grade 2 had a larger negative impact on the PCS in older subjects, whereas it affected the MCS more in younger subjects. First, there are some methodologic issues to dis- CHEST / 131 / 6/ JUNE,

6 Table 3 Physical and Mental SF-12 Scores by Symptoms PCS MCS Symptoms Subjects, No. Mean (SD) p Value* Mean (SD) P Value* Morning cough.1.1 1, (8.8) 51.6 (8.5) Incidence (1.3) 49. (9.4) Remission (8.6) 5.7 (.9) Persistent (11.4) 48. (1.2) Chronic cough.1.1 1, (9.) 51.3 (8.5) Incidence (11.4) 46.8 (1.9) Remission (8.3) 5.9 (9.6) Persistent (11.8) 46.6 (1.9) Phlegm cough.1.1 1, (8.9) 51.5 (8.5) Incidence (1.2) 49. (9.7) Remission (8.9) 51. (9.2) Persistent (11.4) 48.2 (1.3) Wheeze.1.1 1, (9.) 51.4 (8.7) Incidence (1.4) 48.9 (9.8) Remission (9.5) 5.4 (8.5) Persistent (1.7) 48.1 (9.) Dyspnea attaks.1.1 1, (8.5) 51.5 (8.7) Incidence (11.8) 47.5 (9.9) Remission (1.1) 49.6 (8.3) Persistent (11.9) 46.5 (9.8) Dyspnea , (7.7) 51.5 (8.6) Incidence (11.7) 47.6 (1.) Remission (9.3) 49.4 (9.5) Persistent (11.7) 46.6 (1.4) *Based on Kruskal Wallis tests. cuss. The strengths of this study are that it has a longitudinal design, a high response rate, and a randomly sampled community cohort with a wide age span. However, although the study is longitudinal, and true incidence and remission can be examined as predictors of the outcome at follow-up, we only have one time point for HRQoL. Thus, whether QoL has decreased due to the incidence of a symptom, or been stationary low and thereby preceded the incident symptom, cannot be resolved. The concept of HRQoL was developed in the 197s and early 198s, but the extensive use of QoL measurements began in the 199s. 25 Hence, the lack of QoL data in the first phase of this study is due to the state of the art of HRQoL in Second, there are several instruments available for measuring HRQoL. SF-12 has the advantage of being easy to complete in a short amount of time. The SF-12 questionnaire has shown a high degree of correspondence to SF-36 in general population surveys in nine European countries. 26 SF-12 has also been validated against SF-36 and EQ-5D in patient populations with similar results. 27,28 However, because SF-12 only has two summary scales, it does not have an overall HRQoL score, nor does it measure specific domains of HRQoL such as social functioning or other domains found in SF-36. Third, the PCS and MCS scores were not normally distributed. This has prevented some earlier studies of providing multivariate modeling through standard techniques like linear regression. However, with computational advances, robust linear regression is now readily available, which enables multivariate adjustment. The distribution of PCS differed from fairly normal in those with persistent dyspnea and chronic cough to skewed in those without these symptoms and in those experiencing incidence or remission (Fig 1). However, normal distribution in some subgroups still requires statistical models that can take the overall skewedness of the distribution onto account. Fourth, socioeconomic status was assessed in terms of educational level. This is the most commonly used measurement of socioeconomic status in epidemiologic studies, 29 and educational level has been shown to be an independent predictor of respiratory symptoms in a previous study 23 of this cohort Original Research

7 Table 4 Multivariate Robust Linear Regression Analysis of Mean PCS and Mean MCS With Respect to Respiratory Symptoms: Adjusted for Age, Smoking Habits, Pack-Years, Educational Level, and BMI; Significant Interactions Taken Into Account* Variables PCS Coefficient (SE); R 2.318; R MCS Coefficient (SE); R 2.117; R 2.34 Morning cough Incidence.87 (.6).83 (.6) Remission.12 (.7).16 (.8) Persistent 1.2 (.8).62 (.9) Chronic cough Incidence 1.32 (.8) 1.73 (.9) Remission.9 (.8) 1.19 (1.) Persistent 2.36 (1.2).83 (1.4) Phlegm cough Incidence.16 (.6).86 (1.) Remission.33 (.6).31 (1.1) Persistent 1.97 (.7).4 (1.4) Wheeze Incidence.21 (.6).8 (.7) Remission.47 (.6).65 (.7) Persistent 1.2 (.8).53 (.8) Dyspnea attacks Incidence 2.72 (.7) 2.51 (.8) Remission 1.24 (.8) 1.9 (.8) Persistent 3.52 (1.) 2.14 (.9) Dyspnea 2 Incidence 6.39 (.8) 2.52 (.9) Remission.52 (1.) 3.42 (1.4) Persistent 8.73 (1.2) 7.59 (1.6) *Age had significant interactions with wheeze and dyspnea grade 2 for PCS and with dyspnea attacks and dyspnea grade 2 for MCS. The coefficients are given for age 5 years. R 2 value from robust linear regressions with the covariates, without the symptoms in the model. p.1. Fifth, the exact wording of two of the questions on respiratory symptoms was changed between baseline and follow-up (Appendix). For the question on wheeze, the time frame was changed from everwheeze to wheeze during the last 12 months. This is likely to lead to a lower estimate of wheeze at follow-up compared to baseline, hence lowering the incidence and persistence rates. If this were to affect the SF-12 scores, we believe it likely to underestimate the effect of wheeze on the PCS and MCS. To our knowledge, this is the first study to examine the relationship between changes in respiratory symptoms and HRQoL in a general population. Hence, there are not many studies with which to compare. In a Welsh study 13 of an elderly population sample of 5 subjects, breathless subjects had reduced SF-36 scores of MCS and PCS, compared with nonbreathless subjects. In a study 3 of 426 young adults in Melbourne, Australia, having wheeze was associated with lower SF-36 PCS and MCS. In a larger previous community study 14 from Manchester, UK, HRQoL varied with the prevalence of four respiratory symptoms and obstructive airways disease. In this study, 14 having any of the four symptoms was associated with a reduced QoL score for all five domains examined (mobility, self care, usual activities, pain/discomfort, and anxiety/depression), compared to not having the symptom. Due to the skewed distribution of the EQ-5D scores, multivariate adjustments were not made in this study. 14 From studies on patient samples, symptoms have been found to predict a lower HRQoL. From a lung and allergy clinic in Massachusetts, patients with chronic cough had significantly reduced HRQoL scores while symptomatic, compared to after treatment and remission of symptoms. 9 In a sample of COPD patients from Italy, an increase in dyspnea on exertion corresponded with a decrease in HRQoL, measured by St. George Respiratory Questionnaire. 12 And, among subjects with asthma in a South Australian population sample, asthmatics with dyspnea and night awakenings had significantly lower SF-36 PCS and MCS than asthmatics without symptoms. 11 In a retrospective analysis 1 of 27 randomized clinical trials, both lung function impairment and having respiratory symptoms were associated with a decrease in HRQoL. However, comparing results from patient samples to population studies may not be valid. For instance, the impact on a subject s state of mind of having chronic cough may not be the same for an asthmatic who knows why he/she coughs, compared with a subject for whom the cough has an unknown cause. Indeed, in a population sample such as ours, some subjects will know why they have a certain symptom, whereas others will not. We conducted the same multivariate analyses that are presented in Table 4 after exclusion of subjects with self-reported chronic lung disease. Almost no differences were seen in the results (data not shown). This could be due to a larger number of subjects without known chronic lung disease in this general population sample. However, it indicates that having respiratory symptoms is a predictor of reduced HRQoL, regardless of whether one knows the cause or not. The results from the current study show that some symptoms are more potent predictors of a reduced PCS and MCS than others, namely chronic cough, dyspnea attacks, and dyspnea grade 2. Presumably, these symptoms have a larger impact on activities in daily living than a symptom like morning cough, or could be indicators of more serious disease. However, CHEST / 131 / 6/ JUNE,

8 Table 5 Interaction Details for the Physical and Mental Scores PCS, Coefficient (SE) MCS, Coefficient (SE) Variables Subjects, No. 35 yr 65 yr 35 yr 65 yr Wheeze 1,921 Incidence (.7).18 (1.) Remission (.7) 1.6 (1.1) Persistent (.9)*.86 (1.1) Dyspnea attacks 2,22 Incidence (1.) 2.69 (1.1)* Remission (1.2)*.35 (1.1) Persistent (1.3) 3.9 (1.2) Dyspnea 2 2,235 Incidence (1.)* 8. (1.)* 3.93 (1.2)* 1.23 (1.) Remission (1.2) 1.16 (1.9) 5.4 (2.)* 1.6 (1.4) Persistent (1.9)* 11.6 (1.1)* 1.7 (2.2)* 4.46 (1.5)* *p.1. The contrasts for interaction between dyspnea 2 and age (MCS) are given for pack-years because there were significant interactions between dyspnea grade 2 and pack-years. especially dyspnea is a complex symptom because it can be part of several different disorders. The connection between dyspnea and psychological problems like depression, panic disorders, and anxiety is complex. Dyspnea is a core feature in panic attacks and anxiety disorders, 3,31 and conversely people with dyspnea often have panic attacks. The prevalence of panic disorders is higher in subjects with pulmonary disease than in the general population. 32,33 HRQoL has been found to vary with gender, age, and educational level. 34 In addition to adjust for these confounders in the robust linear regression models, we conducted extensive analyses of possible interactions. With gender, no interactions were found. Previous studies on patient samples have hinted at possible gender differences in how respiratory symptoms relate to HRQoL. None of these studies examined changes in respiratory symptoms. Too few studies have been undertaken to resolve whether there are gender differences in how respiratory symptoms relate to HRQoL; however, in this general population study none were found. With age, there were several significant interactions with symptoms affecting HRQoL. Younger subjects with persistent wheeze reported a lower PCS than older subjects with persistent wheeze. Remission of dyspnea attacks was negatively associated with MCS in younger subjects but not in older subjects. And, whereas persistent dyspnea grade 2 had a larger negative impact on PCS in the older subjects compared to the younger subjects, the reverse was true for the MCS. However, the small number of subjects in these groups (Table 5) implies that substantial caution must be taken in interpreting these findings. The larger picture from this study is to be found in the pattern of how changes in respiratory symptoms influence the PCS and MCS. Compared with subjects without symptoms at either time point, subjects with remission of a symptom have about the same HRQoL scores, whereas subjects with incidence or persistence of symptoms have lower HRQoL scores. Subjects with persistent symptoms have lower HRQoL scores than subjects with incident symptoms. Thus, a heavier symptom load has a larger influence on HRQoL. And, with remission of a symptom will subjects have a HRQoL score comparable to subjects without symptoms. A considerable number of subjects have respiratory symptoms, and for many of them this has an impact on their QoL. For some, the symptoms are due to a known chronic disease; for others they are not. Regardless, QoL is affected by respiratory symptoms that underscore the need to diagnose and treat the symptoms properly. Appendix The wording of the questions on respiratory symptoms was identical at baseline and follow-up except for the questions regarding chronic cough and wheezing: 1985 Do you usually cough or clear your throat in the morning? (yes, no) Do you usually have phlegm when coughing? (yes, no) Do you have a daily cough for 3 months altogether during a year? (yes, no) Are you breathless when you climb two flights of stairs at an ordinary pace? (yes, no) [dyspnea grade 2] 1896 Original Research

9 Do you sometimes experience attacks of breathlessness? (yes, no) Do you ever have wheezing in your chest? (yes, no) 1996/1997 Do you have a cough for 3 months altogether during a year? (yes, no) Have you had wheezing in your chest in the last 12 months? (yes, no) ACKNOWLEDGMENT: Borghild Hovland and the late Ms. Bjørg Meidel made significant contributions to the collecting and punching of the data. References 1 Kaplan RM, Ries AL, Reilly J, et al. Measurement of health-related quality of life in the National Emphysema Treatment Trial. Chest 24; 126: Graf J, Koch M, Dujardin R, et al. Health-related quality of life before, 1 month after, and 9 months after intensive care in medical cardiovascular and pulmonary patients. Crit Care Med 23; 31: van den Boom G, Rutten-van Molken MP, Tirimanna PR, et al. Association between health-related quality of life and consultation for respiratory symptoms: results from the DIMCA programme. Eur Respir J 1998; 11: Osman IM, Godden DJ, Friend JA, et al. Quality of life and hospital re-admission in patients with chronic obstructive pulmonary disease. Thorax 1997; 52: Seemungal TA, Donaldson GC, Paul EA, et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 157: Merikallio VJ, Mustalahti K, Remes ST, et al. Comparison of quality of life between asthmatic and healthy school children. Pediatr Allergy Immunol 25; 16: Osman LM, Calder C, Robertson R, et al. Symptoms, quality of life, and health service contact among young adults with mild asthma. Am J Respir Crit Care Med 2; 161: Schlenk EA, Erlen JA, Dunbar-Jacob J, et al. Health-related quality of life in chronic disorders: a comparison across studies using the MOS SF-36. Qual Life Res 1998; 7: French CL, Irwin RS, Curley FJ, et al. Impact of chronic cough on quality of life. Arch Intern Med 1998; 158: Carranza Rosenzweig JR, Edwards L, Lincourt W, et al. The relationship between health-related quality of life, lung function and daily symptoms in patients with persistent asthma. Respir Med 24; 98: Goldney RD, Ruffin R, Fisher LJ, et al. Asthma symptoms associated with depression and lower quality of life: a population survey. Med J Aust 23; 178: Peruzza S, Sergi G, Vianello A, et al. Chronic obstructive pulmonary disease (COPD) in elderly subjects: impact on functional status and quality of life. Respir Med 23; 97: Ho SF, O Mahony MS, Steward JA, et al. Dyspnoea and quality of life in older people at home. Age Ageing 21; 3: Hazell M, Frank T, Frank P. Health related quality of life in individuals with asthma related symptoms. Respir Med 23; 97: Bakke P, Gulsvik A, Lilleng P, et al. Postal survey on airborne occupational exposure and respiratory disorders in Norway: causes and consequences of non-response. J Epidemiol Commun Health 199; 44: Eagan TM, Eide GE, Gulsvik A, et al. Nonresponse in a community cohort study: predictors and consequences for exposure-disease associations. J Clin Epidemiol 22; 55: Gulsvik A, Bakke P, Humerfelt S, et al. Measurements of respiratory symptoms and sample size to detect a given difference between treatment groups in obstructive lung disease. Eur Respir Rev 1991; Welle I, Eide GE, Bakke PS, et al. The single-breath transfer factor for carbon monoxide and respiratory symptoms in a Norwegian community sample. Eur Respir J 1999; 14: Brogger JC, Bakke PS, Gulsvik A. Comparison of respiratory symptoms questionnaires. Int J Tuberc Lung Dis 2; 4: Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996; 34: Sturm R, Wells KB. Does obesity contribute as much to morbidity as poverty or smoking? Public Health 21; 115: Ware JE. How to score the SF-12 physical & mental summary scales. 3rd ed. Lincoln, RI: Quality Metric, Eagan TM, Gulsvik A, Eide GE, et al. The effect of educational level on the incidence of asthma and respiratory symptoms. Respir Med 24; 98: Body mass index. Geneva, Switzerland: World Health Organization, 26. Available at: index.jsp?intropage intro_3.html/. Accessed May 2, Fayers P, Machin D. Quality of life assessment, analysis and interpretation. 1st ed. New York, NY: John Wiley & Sons Ltd, 2 26 Gandek B, Ware JE, Aaronson NK, et al. Cross-validation of item selection and scoring for the SF-12 Health Survey in nine countries: results from the IQOLA Project; International Quality of Life Assessment. J Clin Epidemiol 1998; 51: Macran S, Weatherly H, Kind P. Measuring population health: a comparison of three generic health status measures. Med Care 23; 41: Riddle DL, Lee KT, Stratford PW. Use of SF-36 and SF-12 health status measures: a quantitative comparison for groups versus individual patients. Med Care 21; 39: Liberatos P, Link BG, Kelsey JL. The measurement of social class in epidemiology. Epidemiol Rev 1988; 1: Matheson M, Raven J, Woods RK, et al. Wheeze not current asthma affects quality of life in young adults with asthma. Thorax 22; 57: Anderson DJ, Noyes R Jr, Crowe RR. A comparison of panic disorder and generalized anxiety disorder. Am J Psychiatry 1984; 141: Verburg K, Griez E, Meijer J, et al. Respiratory disorders as a possible predisposing factor for panic disorder. J Affect Disord 1995; 33: Spinhoven P, Ros M, Westgeest A, et al. The prevalence of respiratory disorders in panic disorder, major depressive disorder and V-code patients. Behav Res Ther 1994; 32: Loge JH, Kaasa S. Short form 36 (SF-36) health survey: normative data from the general Norwegian population. Scand J Soc Med 1998; 26: Belloch A, Perpina M, Martinez-Moragon E, et al. Gender differences in health-related quality of life among patients with asthma. J Asthma 23; 4: French CT, Fletcher KE, Irwin RS. Gender differences in health-related quality of life in patients complaining of chronic cough. Chest 24; 125: Wijnhoven HA, Kriegsman DM, Snoek FJ, et al. Gender differences in health-related quality of life among asthma patients. J Asthma 23; 4: CHEST / 131 / 6/ JUNE,

10 Changes in Respiratory Symptoms and Health-Related Quality of Life * Marianne Voll-Aanerud, Tomas M. L. Eagan, Tore Wentzel-Larsen, Amund Gulsvik and Per S. Bakke Chest 27;131; ; Prepublished online May 15, 27; DOI /chest This information is current as of May 15, 211 Updated Information & Services Updated Information and services can be found at: References This article cites 33 articles, 11 of which can be accessed free at: Cited Bys This article has been cited by 1 HighWire-hosted articles: Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: Reprints Information about ordering reprints can be found online: Citation Alerts Receive free alerts when new articles cite this article. To sign up, select the "Services" link to the right of the online article. Images in PowerPoint format Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online figure for directions.