Ferenc Macsali

Early Age at Menarche, Lung Function, and Adult Asthma

RATIONALE hormonal and metabolic status appears to influence lung health in women, and there are findings suggesting that early menarche may be related to asthma, cardiovascular disease, diabetes, and breast cancer. OBJECTIVES this study investigates whether age at menarche is related to adult lung function and asthma. METHODS among participants in the European Community Respiratory Health Survey II, 3,354 women aged 27-57 years from random population samples in 21 centers responded to a questionnaire concerning womens health (1998-2002). Of these women, 2,873 had lung function measurements, 2,136 had measurements of bronchial hyperreactivity, and 2,743 had IgE measurements. Logistic, linear, and negative binomial regression analyses included adjustment for age, height, body mass index, education, smoking, family size, and center. MEASUREMENTS AND MAIN RESULTS FEV(1) and FVC were lower and asthma was more common in women with early menarche. Women reporting menarche at age 10 years or less, as compared with women with menarche at age 13 years (reference category), had lower FEV(1) (adjusted difference, -113 ml; 95% confidence interval [CI], -196 to -33 ml) and FVC (-126 ml; 95% CI, -223 to -28 ml); also lower FEV(1) expressed as a percentage of the predicted value (-3.28%; 95% CI, -6.25 to -0.30%) and FVC expressed as a percentage of the predicted value (-3.63%; 95% CI, -6.64 to -0.62%). Women with early menarche more often had asthma symptoms (odds ratio, 1.80; 95% CI, 1.09-2.97), asthma with bronchial hyperreactivity (odds ratio, 2.79; 95% CI, 1.06-7.34), and higher asthma symptom score (mean ratio, 1.58; 95% CI, 1.12-2.21). CONCLUSIONS women with early menarche had lower lung function and more asthma in adulthood. This supports a role for metabolic and hormonal factors in womens respiratory health.

Validity of the diagnosis of pre‐eclampsia in the Medical Birth Registry of Norway

Evaluating the validity of pre‐eclampsia registration in the Medical Birth Registry of Norway (MBRN) according to both broader and restricted disease definitions.

Oral contraception, body mass index, and asthma: a cross-sectional Nordic-Baltic population survey.

BACKGROUND Emerging evidence suggests that sex steroid hormones may influence airways obstruction, and that metabolic status may modify potential effects. OBJECTIVE This study investigated the association between use of oral contraceptive pills (OCPs) and asthma in a Nordic-Baltic population-based study, while taking into account possible interplay with body mass index (BMI). METHODS Postal questionnaires were sent to subjects in Denmark, Estonia, Iceland, Norway, and Sweden from 1999 to 2001 (response rate in women, 77%). Pregnant women, women using hormone replacement therapy, and women >45 years were excluded. Analyses included 5791 women 25 to 44 years old, of whom 961 (17%) used OCP. Logistic regression analyses included adjustment for smoking, irregular menstruation, BMI, age, type of dwelling, and center. RESULTS Oral contraceptive pills were associated with increased risk for asthma (odds ratio, 1.42; 95% CI, 1.09-1.86), asthma with hay fever (1.48; 1.08-2.03), wheeze with shortness of breath (1.27; 1.02-1.60), hay fever (1.25; 1.06-1.48), and >/=3 asthma symptoms (1.29; 1.05-1.58). The findings were consistent between centers. The associations were present only among normal weight women (BMI 20-25 kg/m(2), asthma: 1.45; 1.02-2.05) and overweight women (BMI >25kg/m(2): 1.91; 1.20-3.02), but not among lean women (BMI <20 kg/m(2): 0.41; 0.12-1.40). Interaction between BMI and OCP in association with asthma was significant (P(interaction) < .05). CONCLUSIONS Women using oral contraceptive pills had more asthma. This was found only in normal weight and overweight women, indicating interplay between sex hormones and metabolic status in effect on the airways. The findings originate from a cross-sectional postal survey and should be interpreted with caution; it is recommended that asthma symptoms are included in clinical trials of oral contraception.

Perimenstrual increase in bronchial hyperreactivity in premenopausal women: Results from the population-based SAPALDIA 2 cohort

BACKGROUND Studies on perimenstrual asthma are inconsistent, and different methodologies limit comparisons. OBJECTIVE To investigate cyclic variations in bronchial hyperreactivity (BHR) to methacholine in premenopausal women in a population-based cohort and assess effect modification by oral contraceptives (OCs). METHODS Day of menstruation cycle at the time of methacholine challenge was calculated in 571 menstruating women without hormonal treatment, age 28 to 58 years, on the basis of questionnaire data from the Swiss cohort study on Air Pollution And Lung Disease In Adults (SAPALDIA) cohort 2001/2002. A window of risk was defined 3 days before and after the first day of menstruation. Logistic and linear regression analyses were performed adjusting for main predictors of BHR and stratifying for asthma status. The impact of OCs was studied in the same sample enlarged by 130 women taking OCs. RESULTS The prevalence of BHR was 13% (fall of > or =20% in FEV(1) up to a maximal cumulative dose of 2 mg), and 6% had asthma. A total of 143 women had undergone methacholine challenge within the risk window. We observed a significant increase in BHR within the window of risk (odds ratio [OR], 2.3; 95% CI, 1.27-4.29). A cyclic association pattern was confirmed by trigonometric functions. Effect modification by asthma status and oral contraceptive use was found, with lower OR in subjects without asthma and OR <1 in women using OCs. CONCLUSION The data provide evidence of a systematic variation in BHR during the menstruation cycle, supporting the hypothesis of a hormonal influence. OCs appear to have a protective effect. Cyclicity of BHR could be of clinical importance in view of future medication recommendations and timing of respiratory function tests in women.

Respiratory health in women: from menarche to menopause

Gender differences in respiratory health have, in recent years, been the focus of considerable scientific effort. This paper reviews recent literature on respiratory health in women in relation to age at menarche, menstrual cycle, irregular menstruation, polycystic ovarian syndrome, menopause and exogenous sex hormones. This literature provides substantial evidence that hormonal status plays an important role for respiratory health in women. Effects of hormonal status on the airways often appear to be heterogeneous and recent literature in particular suggests that the interplay between hormonal and metabolic factors is important. A view to developmental factors may also be relevant for the understanding of respiratory health according to hormonal status in women. Further knowledge of respiratory health in women holds interesting potential for intervention and personalized treatment.

Menstrual cycle and respiratory symptoms in a general Nordic-Baltic population.

RATIONALE There is little knowledge of variations in respiratory symptoms during the menstrual cycle in a general population, and potential modifying factors are not investigated. OBJECTIVES To investigate menstrual cycle variation in respiratory symptoms in a large general population, using chronobiology methodology, and stratifying by body mass index (BMI), smoking, and asthma status. METHODS A total of 3,926 women with regular cycles less than or equal to 28 days and not taking exogenous sex hormones answered a postal questionnaire regarding the first day of their last menstruation and respiratory symptoms in the last 3 days. Moving 4-day means were computed to smooth uneven records of daily sampling; best-fitting 28-day composite cosine curves were applied to each time series to describe rhythmicity. MEASUREMENTS AND MAIN RESULTS Significant rhythmic variations over the menstrual cycle were found in each symptom for all subjects and subgroups. Wheezing was higher on cycle Days 10-22, with a midcycle dip near the time of putative ovulation (approximately Days 14-16) in most subgroups. Shortness of breath was higher on days 7-21, with a dip just before midcycle in many subgroups. Cough was higher just after putative ovulation for subjects with asthma, BMI greater than or equal to 23 kg/m(2), and smokers, or just before ovulation and menses onset for low symptomatic subgroups. CONCLUSIONS Respiratory symptoms varied significantly during the menstrual cycle and were most frequent from the midluteal to midfollicular stages, often with a dip near the time of ovulation. The patterns varied by BMI, smoking, and asthma status. These relations link respiratory symptoms with hormonal changes through the menstrual cycle and imply a potential for individualized chronotherapy for respiratory diseases.

Respiratory health in cleaners in Northern Europe : is susceptibility established in early life?

Rationale There is some evidence that maternal smoking increases susceptibility to personal smoking’s detrimental effects. One might question whether early life disadvantage might influence susceptibility to occupational exposure. Objectives In this cross-sectional study we investigated respiratory symptoms, asthma and self-reported chronic obstructive pulmonary disease (COPD) as related to working as a cleaner in Northern European populations, and whether early life factors influenced susceptibility to occupational cleaning’s unhealthy effects. Methods The RHINE III questionnaire study assessed occupational cleaning in 13,499 participants. Associations with respiratory symptoms, asthma and self-reported COPD were analysed with multiple logistic regressions, adjusting for sex, age, smoking, educational level, parent´s educational level, BMI and participating centre. Interaction of occupational cleaning with early life disadvantage (maternal smoking, severe respiratory infection <5 years, born during winter months, maternal age at birth >35 years) was investigated. Main Results Among 2138 ever-cleaners the risks of wheeze (OR 1.4, 95% CI 1.3–1.6), adult-onset asthma (1.5 [1.2–1.8]) and self-reported COPD (1.7 [1.3–2.2]) were increased. The risk increased with years in occupational cleaning (adult-onset asthma: ≤1 year 0.9 [0.7–1.3]; 1–4 years 1.5 [1.1–2.0]; ≥4 years 1.6 [1.2–2.1]). The association of wheeze with cleaning activity ≥4 years was significantly stronger for those with early life disadvantage than in those without (1.8 [1.5–2.3] vs. 1.3 [0.96–1.8]; pinteraction 0.035). Conclusions Occupational cleaners had increased risk of asthma and self-reported COPD. Respiratory symptom risk was particularly increased in persons with factors suggestive of early life disadvantage. We hypothesize that early life disadvantage may increase airway vulnerability to harmful exposure from cleaning agents later in life.

Hormonal factors and respiratory health in women – a review

Sex hormones appear to play an important role in the lung health of women. This is, however, poorly understood and, in most aspects, poorly investigated; and the literature has been contradictory and confusing. This review presents recent research concerning the involvement of sex hormones in respiratory health of adult women, using the population surveys European Community Respiratory Health Survey and Respiratory Health in Northern Europe.

Polycystic ovary syndrome, body mass index and hypertensive disorders in pregnancy

OBJECTIVE Some studies of women with polycystic ovary syndrome (PCOS) report increased prevalence of hypertensive disorders in pregnancy, while others do not. Several of these studies do not control for obesity. We aimed to study whether PCOS is associated with hypertensive disorders in pregnancy and whether it is dependent on body mass index (BMI). STUDY DESIGN We present a cross-sectional analysis of 3732 women from Denmark, Estonia, Iceland, Norway and Sweden, born in 1945-72, who participated in the Respiratory Health In Northern Europe (RHINE) study and answered an extensive womens health questionnaire on menstruation, PCOS, infertility, pregnancy history and childbirth. The main outcome measurement was hypertensive disorders of pregnancy. We adjusted for smoking, age, infertility treatment and study center. Effect modification by BMI was assessed. RESULTS PCOS was related to hypertensive disorders in pregnancy with a relative risk (RR) of 1.62 (95% CI 1.09-2.42). This relationship was found among underweight women with a BMI of <18.5 kg/m2 [RR = 5.2 (95% CI 1.66-16.5)] and obese women with a BMI of ≥30 kg/m2 [RR = 2.36 (95% CI 1.29-4.31)], but not among normal-weight women, BMI 18.5-25 kg/m2 [1.08 (0.53-2.20)], or overweight women, BMI 25-30 kg/m2 [1.24 (0.50-3.08)] (p-interaction = 0.041). CONCLUSION Polycystic ovary syndrome is associated with hypertensive disorders in pregnancy. This association only occurs among underweight and obese women and not among normal-weight and slightly overweight women.