ARTICLE IN PRESS Respiratory Medicine (2007) 101, 896–902
Female gender is associated with higher incidence and more stable respiratory symptoms during adolescence Elin Tollefsena,b,, Arnulf Langhammerb, Pa ˚l Romundstadc, Leif Bjermerd, Roar Johnsenc, Turid L. Holmenb a
Department of Respiratory Medicine, Trondheim University Hospital, Trondheim, Norway The Nord-Trøndelag Health Study Research Centre (HUNT), Faculty of Medicine, The Norwegian University of Science and Technology, Verdal, Norway c Faculty of Medicine, Department of Public Health and General Practice, Norwegian University of Science and Technology, MTFS, Røde Kors-bygget, Eirik Jarlsgt. 14, N-7489 Trondheim, Norway d Department of Respiratory Medicine and Allergy, University Hospital of Lund, Lund, Sweden b
Received 15 June 2006; accepted 25 September 2006 Available online 3 November 2006
KEYWORDS Adolescence; Asthma; Incidence; Prospective study; Wheeze
Summary Childhood asthma and wheeze is more common among boys than girls, while the opposite is found in adults. The main objective was to study the incidence and the course of wheeze and asthma during adolescence with focus on gender differences. In addition, we explored associations between lifestyle factors at baseline and wheeze at follow-up. A total of 2399 adolescents answered validated questionnaires on respiratory symptoms and lifestyle in 1995–1997 (13–15 years) and at follow-up in 2000–2001 (17–19 years). The risk of reporting wheeze and asthma at follow-up was greater in girls compared to boys among subjects reporting no respiratory symptoms at baseline; Relative risk: 1.4 and 2.4, respectively. More girls than boys reported current wheeze at follow-up, both among those with current wheeze (girls 60%, boys 48%) and previous wheeze (girls 33%, boys 28%) at baseline. In girls, development of current wheeze was significantly associated with current smoking (OR ¼ 2:8) and stable current wheeze was significantly associated with overweight (OR ¼ 2:4). Similar associations were not significant in boys. More girls than boys developed wheeze, had stable wheeze or had relapse of previous symptoms during the four year follow-up. The impact of smoking and overweight may put girls at a higher risk of respiratory symptoms than boys. Awareness of the gender
Corresponding author. Faculty of Medicine, Department of Public Health and General Practice, Norwegian University of Science and
Technology, MTFS, Røde Kors-bygget, Eirik Jarlsgt. 14, N-7489 Trondheim, Norway. Tel.: +47 7359 8895; fax: +47 7359 2517. E-mail address: [email protected]
(E. Tollefsen). 0954-6111/$ - see front matter & 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.rmed.2006.09.022
ARTICLE IN PRESS Adolescent respiratory symptoms
897 difference in respiratory symptoms is important for diagnosis and preventive strategies during adolescence. & 2006 Elsevier Ltd. All rights reserved.
Introduction Previous studies present a considerable variability of incidence and risk factors for wheeze and asthma between gender and age groups. Estimated annual incidence of doctor diagnosed asthma has been found to range from 0.6 to 29.5 per 1000 person years in 19 reviewed papers.1 The relation between gender and wheeze incidence is dependent of age,2 as childhood wheeze and asthma is more common among boys than girls,3 while the opposite is found in adults.4–6 Gender differences regarding wheeze and asthma during adolescence is scarcely described in previous papers. The male disadvantage for asthma seems to disappear during puberty, but the underlying mechanism is unknown. Hormonal fluctuations, airway calibre and bronchial hyper-reactivity have been discussed as possible reasons for the gender difference,7,8 but so far their contribution is uncertain. Reporting of asthma symptoms may also be affected by the psychological and social consequences of puberty, with girls reporting more symptoms in general with age.9 However, different susceptibility to lifestyle factors may also contribute to the gender difference.10 This was supported by a cross-sectional study of the Young-HUNT population in 1995–1997, when also current wheeze and asthma was found to be significantly more prevalent in girls compared to boys.11 The main objective of this paper was, in a longitudinal design, to study the incidence and the course of wheeze and asthma during adolescence with focus on gender differences. In addition, we explored associations between lifestyle factors at baseline and wheeze at follow-up.
Material and methods Study population The county of Nord-Trøndelag in Norway has about 127,000 inhabitants. The Nord-Trøndelag Health Study (HUNT), conducted in 1995–1997, invited all inhabitants 13 years and older. Students 13–19 years participated in the youth part of the study; Young-HUNT 1. In 2000–2001, the youngest students from Young-HUNT 1 were invited to a follow-up study; Young-HUNT 2. The present paper presents data from those participating at both baseline (age 13–15 years) in 1995–1997 and at follow-up (age 17–19 years) in 2000–2001.
Methods The students completed a comprehensive self-administered questionnaire during one school hour in an exam setting. The questionnaire included questions on respiratory symptoms based on the International Study of Asthma and Allergy in Childhood (ISAAC) questionnaire.12 Within a month after completing the questionnaire, standardized measures of
height and weight were performed. Students were light clothed without shoes. Height was read to the nearest cm and weight to the nearest 12 kg. The questionnaires and measurement procedure were identical at both baseline and follow-up.
Ethics All participants, and parents of children under the age of 16 years, signed a written consent to take part in the study. The study was approved by the Regional Committee for Medical Research Ethics and the Norwegian Data Inspectorate Board.
Variables Current wheeze was defined as ‘‘wheeze ever’’ and ‘‘wheeze last 12 months’’. Previous wheeze was defined as ‘‘wheeze ever’’ but ‘‘no wheeze last 12 months’’. Current asthma was defined as ‘‘wheeze last 12 months’’ and ‘‘asthma diagnosed by a doctor’’. Environmental smoking was defined as exposure to smoking at home by mother, father or siblings. Current smoking was defined as yes to ‘‘daily or occasional smoking’’ or reported number of cigarettes smoked daily. In addition, subgroups of smoking adolescents were defined as to yes to ‘‘daily smoking and reported number of cigarettes’’ and yes to ‘‘occasional smoking’’. To define BMI we used the International Obesity Task Force described by Cole et al.13 Each gender and age (by half year) has percentile cut-off points for overweight and obesity. At age 18, adult cut-off points are used, overweight being defined as BMIX25 kg/m2. The overweight group included those defined as overweight or obese. The question on physical activity, ‘‘outside of school, how many days a week do you perform sports or exercise until you get short of breath and/or sweaty’’, has been used in different countries14,15 and involves frequency, endurance and intensity. Those who exercised less than twice a week were defined as having low physical activity.
Statistical analysis Stata Statistical Software Package for Windows version 8.0 (Stata Corporation, College Station, TX 77845) was used for computation of cumulative incidence, relative risk and Poisson exact 95% confidence interval (95% CI). Otherwise SPSS for windows version 13.0 (SPSS Inc, Chicago, IL) was used. All analyses were either stratified or adjusted by gender. Separate logistic regression models were used for those who reported no respiratory symptoms and current wheeze at baseline, both with current wheeze at follow-up as dependent variable. The independent variables tested in both models were baseline current smoking, environmental smoking, overweight and physical activity. Interaction between gender and independent variables were also tested
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in the models. Additionally, age at baseline was tested in the models, but did not contribute significantly nor changed the estimates and was therefore not included in the final models. Also, the categories ‘‘no smoking at baseline and current smoking at follow-up’’, ‘‘current smoking at both baseline and follow-up’’, ‘‘normal weight at baseline and overweight at follow-up’’ and ‘‘overweight at both baseline and follow-up’’ were tested in the models, but did not influence the result. In the logistic regression analyses missing data were recoded to ‘‘no’’. This did not influence the result. All hypothesis testing was conducted using a 5% significance level and a two-sided alternative hypothesis. Odds ratio was completed with 95% confidence interval (CI) and P-value.
Results The participation rate was 92% at baseline in 1995–1997 and 85% at follow-up in 2000–2001. A total of 2399 teenagers (girls 53.5%) participated in both studies; the adolescents being 13–15 years (mean age 13.9) at baseline and 17–19 years (mean age 17.8) at follow-up.
The course of respiratory symptoms during adolescence Different patterns regarding symptoms and disease were found in girls compared to boys. More girls than boys being asymptomatic at baseline reported current wheeze at follow up (girls 21.5% 95% CI (18.6–24.4), boys 12.5% 95% CI (10.2–14.8)). Girls also reported significantly more wheeze at both baseline and follow-up than boys (girls 60.1% 95% CI (55.0–65.3), boys 47.7% 95% CI (40.7–54.7)) and more frequent transitions from previous wheeze to current wheeze during follow-up (girls 32.7% 95% CI (25.3–40.1), boys 28.3% 95% CI (20.2–36.4)) (Fig. 1). A similar pattern was found regarding current asthma. More girls than boys being asymptomatic at baseline reported current asthma at follow-up (girls 4.4% (95% CI 3.0–5.9, boys 1.8% (95% CI 0.9–2.7)). Current asthma at baseline was reported by 94 girls and 66 boys. A significant gender difference was found for reporting current asthma at both baseline and follow-up (girls 77.7% (95% CI 69.3–86.1), boys 54.5% (95% CI 42.5–66.5)). Of those who reported current wheeze but no current asthma at baseline more girls than boys reported current asthma at follow-up (girls 11.1% (95% CI 7.1–15.1), boys 4.7% (95% CI 1.0–8.4)).
Cumulative incidence and trends in prevalence
Associations between wheeze and lifestyle factors
The mean follow-up time was 3.9 years. Among subjects reporting no respiratory symptoms at baseline, the risk (cumulative incidence) for wheeze was 29.8 and 21.2 per 1000 person years for girls and boys, respectively, and the risk (cumulative incidence) for asthma was 5.6 and 2.3 per 1000 person years for girls and boys, respectively, at followup. Relative risk for girls, compared to boys, was 1.4 (95% CI 1.1–1.8) and 2.4 (95% CI 1.2–4.9) for the reporting of wheeze and asthma, respectively. At baseline, the prevalence of current wheeze was significantly higher in girls compared to boys, while no significant difference by gender was found regarding current asthma. At follow-up, girls reported significantly more current wheeze and current asthma than the boys (Table 1). Even at age 13, current wheeze was significantly more prevalent in girls (23.9% (95% CI 19.7–28.1)) than boys (14.8% (95% CI 11.2–18.4)). Although not significant, prevalence of current asthma showed a similar tendency at age 13 (girls 6.7% (95% CI 4.3–9.2), boys 4.5% (95% CI 2.4–6.6)).
Girls and boys were similarly exposed to environmental smoking and they were equally represented in the overweight group at both baseline and follow-up. The girls reported to be less physical active than boys at both baseline and follow-up. The proportion of current smokers was significantly higher among girls than boys at both baseline and follow-up (Table 2). The same pattern was found when dividing smokers into subgroups of ‘‘daily smoking’’ and ‘‘occasional smoking.’’ In asymptomatic teenagers who, during follow-up, developed respiratory symptoms, there was a positive association with current smoking at baseline, significant in girls only (OR ¼ 2:8) (Table 3). In addition, we observed a positive association with environmental smoking at baseline for both genders, not significant in girls (girls OR ¼ 1:3, boys OR ¼ 1:8) (Table 3). The interaction between gender and environmental smoking was not significant when both genders were included in the same model, indicating no gender difference. Among these teenagers, no association
Table 1 Prevalence of current wheeze and current doctor diagnosed asthma in adolescence (n ¼ 2399) at baseline and at four year follow-up, stratified by gender. Girls n ¼ 1284
Current wheeze Current doctor diagnosed asthma
Boys ¼ 1115
ARTICLE IN PRESS Adolescent respiratory symptoms
No respiratory symptoms ever 771 (60.5%)
Current wheeze 348 (27.3%) Previous wheeze 156 (12.2%)
60.1% 39 . 9% 3
% 2 .7
No respiratory symptoms ever 605 (47.5%)
No respiratory symptoms ever 794 (71.5%)
Current wheeze 426 (33.4%)
Current wheeze 197 (17.7%)
Previous wheeze 244 (19.1%)
Previous wheeze 120 (10.8%)
87.5% 12.5 % 47.7% 52 .
No respiratory symptoms ever 695 (62.6) Current wheeze 227 (20.4%) Previous wheeze 189 (17.0%)
Figure 1 The course of a self-reported respiratory symptoms during adolescence (n ¼ 2399) at baseline (13–15 years) and at 4 year follow-up (17–19 years), stratified by gender. (A) Girls; (B) boys.
Table 2 Prevalence of self-reported lifestyle and measured overweight in adolescence (n ¼ 2399) at baseline and at four year follow-up, stratified by gender. Girls n ¼ 1284
Boys ¼ 1115
Current smoking Daily smoking Occasional smoking Environmental smoking Overweight Low physical activity
12.5 4.2 8.7 49.7 14.3 27.5
(10.7–14.3) (3.1–5.3) (7.2–10.2) (47.0–52.4) (12.4–16.2) (25.1–29.9)
40.3 23.6 17.3 46.9 12.7 45.8
(37.6–43.0) (21.3–25.9) (15.2–19.4) (44.2–49.6) (10.9–15.5) (43.1–48.5)
7.6 3.5 4.5 47.9 14.8 21.0
(6.0–9.2) (2.4–4.6) (3.3–5.7) (45.0–50.8) (12.7–16.9) (18.6–23.4)
31.9 16.8 16.1 46.1 13.5 35.8
(29.2–34.6) (14.6–19.0) (13.9–18.3) (43.2–49.0) (11.5–15.5) (33.0–38.6)
Current smoking was defined as yes to ‘‘daily or occasional smoking’’ or reported number of cigarettes smoked daily.
Table 3 Associations between lifestyle factors at baseline and current wheeze at follow-up in separate regression models, adjusted odds ratio with 95% CI, stratified by gender. Lifestyle factors at baseline
Current smoking Environmental smoking Overweight Low physical activity
No respiratory symptoms at baseline and current wheeze at follow-up
Current wheeze at both baseline and follow-up
Girls n ¼ 724
Girls n ¼ 348
Boys n ¼ 753
Boys n ¼ 197
Adjusted by self-reported current smoking, environmental smoking and low physical activity, and measured overweight at baseline.
was found neither between overweight nor physical activity at baseline and the development of respiratory symptoms at follow-up. Respiratory symptoms at both baseline and follow-up were significantly associated with overweight at baseline in girls only (OR ¼ 2:4) (Table 3). Current smoking was
positively, but not significantly, associated with stable respiratory symptoms in both genders. Environmental smoking was positively, but not significantly, associated with stable respiratory symptoms in boys only. No association was found between low physical activity and respiratory symptoms for either gender.
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Discussion In this population-based follow-up study of 2399 teenagers, different patterns regarding respiratory symptoms was found in girls and boys. The risk for wheeze was greater in girls compared to boys, more girls than boys reported stable wheeze or relapse of previous symptoms during the four year follow-up. In girls, development of current wheeze was significantly associated with current smoking and stable current wheeze was significantly associated with overweight. Similar associations were not significant in boys. The strengths of the study were the large number of participants from an unselected population and a high respond rate. Self-reported data may be a limitation to the study, but the questions on respiratory symptoms have previously been validated, definitions chosen for current wheeze and current asthma were strictly defined, confidentiality was stressed and there was a consistent reporting of health problems, medication and the need for health services (data not shown). A four year follow-up period may be short for a prospective design. However, the focus of the study was on the teenaged group, which provided a limited time prospective.
The risk (cumulative incidence) of wheeze Few previous papers have addressed gender differences regarding wheeze and asthma during adolescence. The present finding of a higher cumulative incidence and a higher relative risk for developing both wheeze and asthma in girls compared to boys confirmed the results from Anderson et al.2 who reported that asthma incidence was greater in boys up to age 16, yet was greater among girls between age 17–23. The incidence of wheeze in other age groups is referred to in several papers,4,6,16 however, any potential inconsistency in reporting is not found to be discussed in previous literature. In the present study, there was an inconsistency for self-reported wheeze, but not for asthma, at baseline and follow-up. Totally 135 adolescents reported current wheeze at baseline and no respiratory symptoms ever at follow-up. This may be due to the possibility that wheeze is a fluctuating symptom with varying duration and severity and thereby less optimal for computation of incidence. In our data set, excluding these teenagers did not influence the results. The trend in prevalence with more girls reporting current wheeze by age compared to boys corresponded to the significant gender difference in risk of wheeze. The prevalence of reported wheeze varies between countries.17,18 Venn et al.,19 in a study from 1998, reported a prevalence of wheeze at age 11 of 19.0% for boys and 17.2% for girls, in contrast to 14.5% and 22.0% at age 16. Our study corroborates the above findings of an age-dependent gender difference. However, in the present study, girls already at the age of 13 reported a higher prevalence of current wheeze and current asthma than boys. Without data from age 12 and younger, our findings cannot conclude as to a particular age for the change in gender predominance. However, the findings might suggest that the feasible transition point from male to female predominance of
E. Tollefsen et al. wheeze and asthma take place earlier than the teenage years. According to Braun-Fahrlander et al.20 the prevalence of asthma seemed to reach a plateau during the 1990s. Due to a too short time period between the two surveys, the present data collection does not have enough power to reveal any significant change in prevalence trend. However, a significant different pattern by gender could indicate an ongoing increase in the prevalence of asthma in girls, but not in boys.
The course of respiratory symptoms during adolescence There was a consistency as regards to the gender differences in the course of respiratory symptoms during follow-up. Compared to girls, fewer boys developed wheeze, had stable wheeze or had relapses of previous wheeze during adolescence. Wool et al. suggest that girls and women are more aware and sensitive to their bodies, more accepting of a disease status and more willing to talk about experienced symptoms, than males.21 The awareness and sensitiveness of symptoms may influence the gender difference in selfreporting of respiratory symptoms in this study. However, the consistency of the results may indicate a true gender difference. The consistency in the self-reported findings may also reduce the likelihood of the possible bias of Yentl syndrome,9 described as females in general being underdiagnosed and undertreated compared to males. Improved diagnostic criteria, increased awareness of symptoms, and change in the willingness of doctors to diagnose asthma over recent years22,23 is not likely to bias the result of a study with such short duration as the present one.
Associations between wheeze and lifestyle factors Genuneit et al.24 recently stated that active smoking increased the incidence of wheeze and asthma during adolescence in both genders. In our study population of asymptomatic teenagers at baseline, the development of respiratory symptoms during follow-up was a significantly associated with current smoking in girls only. This finding was independent of the fact that the proportion of current smokers was significantly higher among girls than boys. The possibility that adolescent females have a lower threshold for developing respiratory symptoms when exposed to current tobacco smoking than adolescent males is previously debated by Holmen et al.10 The possible causal association between environmental smoking and respiratory symptoms has been debated in previous papers with different conclusions; some are in support of the assumption that environmental smoking is a risk factor for wheeze, while others found no such evidence.25–27 In the present study, both genders showed a positive association between development of respiratory symptoms and environmental smoking; a result in favour of a possible connection between the two. Environmental smoking was defined as exposure to smoking at home by mother, father or siblings. A limitation to this definition is the unawareness of exposure and possible impact of smoking by friends during adolescent years.
ARTICLE IN PRESS Adolescent respiratory symptoms Girls and boys were equally represented in the overweight group at both baseline and follow-up. However, the impact of overweight in connection with respiratory symptoms seems to have a different importance in girls compared to boys as the reporting of respiratory symptoms at both baseline and follow-up showed a significant association with overweight in girls only. A previous study of children aged 7–12 years found a higher BMI to be associated with a higher prevalence of wheeze and that this association was stronger in girls than in boys.28 In adults aged 20–64 years, obesity was found to be a risk factor for asthma in women but not in men.29 Other studies report an association between obesity and asthma for both genders.30,31 Despite these reports, the effect of being overweight as a risk factor for airway obstructive diseases is not clear. Adolescents with wheeze may be more likely to avoid exercise, adopt a sedentary lifestyle and, in turn, gain weight. However, the gender difference with a stronger association between wheeze and overweight in girls compared to boys may suggest the possibility that female hormones may directly or indirectly be involved in the causal pathway that relates overweight to asthma. Levels of estrogen are related to body fat mass.32 Castro-Rodriguez et al.33 found that the association between overweight status and asthma was stronger among girls whose puberty started before the age of 11 years than among those girls whose puberty stared later. An association between low physical activity and wheeze has been described in younger children.34 The possibility for a similar association in adolescence is not found to be described in previous papers. In the present study, no significant association was found between low physical activity and respiratory symptoms for either gender. Our findings support a transition from male to female predominance of respiratory symptoms, and describe this transition during adolescence. The impact of lifestyle factors such as smoking and overweight may indicate the need for different preventive strategies during adolescence, dependent of gender.
Conclusion Among Norwegian adolescents the risk for wheeze was greater in girls compared to boys. More girls than boys reported stable wheeze or relapse of previous symptoms during the four year follow-up. The impact of smoking and overweight may put girls at a higher risk of respiratory symptoms than boys.
Acknowledgments This study was supported by the Norwegian Research Council, the Norwegian State Department of Social and Health Affairs, and the county of Nord-Trøndelag, Norway.
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