1 Department of Obstetrics and Gynaecology, 2 Department of Internal Medicine, San Martino Hospital and University of Genoa, Largo R.Benzi 1, 16132 Genoa, Italy and 3 University Department of Obstetrics and Gynaecology, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK
4 To whom correspondence should be addressed. E-mail: simone.ferrero{at}fastwebnet.it
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Abstract |
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Key words: asthma/endometriosis/quality of life
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Introduction |
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A recent cross-sectional survey conducted in the USA by the Endometriosis Association (Sinaii et al., 2002) suggested that women with endometriosis have higher rates of asthma than the general population. This survey also found higher rates of autoimmune disorders (i.e. hypothyroidism, systemic lupus erythematosus, Sjogrens syndrome), fibromyalgia, and chronic fatigue syndrome in women with endometriosis. Unfortunately, this study was characterized by several limitations: data were obtained from a self-administered questionnaire, the general population prevalences used for comparison were not limited to women, nor to those of reproductive age, and co-morbidity comparisons were not adjusted for potential confounders (Missmer and Cramer, 2005
).
The current prospective study aims to investigate asthma prevalence and severity in women with and without endometriosis undergoing surgery at our Institution.
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Materials and methods |
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Diagnosis of bronchial asthma was based on the American Thoracic Society (1987) criteria; briefly, bronchial asthma was diagnosed as the presence of symptoms of episodic wheezing, coughing and shortness of breath responding to bronchodilators and reversible airflow obstruction documented in at least one previous pulmonary function study.
All women were interviewed on demographic and health behaviours; respiratory symptoms and medication use were investigated in subjects suffering asthma. Patients were classified according to their smoking habits: current smokers were defined as women who reported smoking cigarettes at the time of the survey; ex-smokers were those who reported smoking cigarettes in the past, but who were not smoking at the time of survey; otherwise, subjects were classified as non-smokers.
Based on the clinical features and on the medication regimen that was used (if any), asthma severity was classified in four categories (intermittent, mild persistent, moderate persistent, severe persistent) according to the 2002 Global Initiative for Asthma guidelines (National Heart, Lung, and Blood Institute, National Institutes of Health, 2002). Asthmatic patients who underwent surgery before December 2002 were retrospectively classified; all other patients were classified before surgery.
Asthmatic patients completed the Living with Asthma Questionnaire (LWAQ), designed to evaluate patients subjective experiences with asthma, including both functional limitation and distress (Hyland, 1991; Hyland et al., 1991
, 1994
; Hyland and Crocker, 1995
; Rutten-van Molken et al., 1995
). The LWAQ is a 68-item self-administered questionnaire; examples of items are: I feel inadequate because of my asthma, I can walk up a flight of stairs without stopping, and I tend to cough a lot at night. Answers are scored from 0 to 2 (from no impairment to maximum impairment). The total score of the LWAQ is calculated and a higher score indicates worse health status; the LWAQ is separated into four constructs: avoidance, distress, preoccupation and activities. The LWAQ has been shown to be reliable and valid (Hyland, 1991
; Hyland et al., 1991
).
Patients were classified according to the presence of endometriosis; the diagnosis of endometriosis was always confirmed by the histological examination of specimens removed at surgery. The extent of endometriosis was scored according to the revised criteria of the American Fertility Society (1985) (rAFS). None of the patients included in the control group had previously undergone surgical treatment for endometriosis.
The study was approved by the local Institutional Review Board and each participant gave written informed consent.
Statistical analysis
A power calculation had been undertaken to determine an appropriate sample size to confirm the findings reported by Sinaii et al. (2002). This power calculation indicated that
400 patients in each group would be necessary to detect a 7% difference in asthma prevalence between women with and without endometriosis (12 and 5% respectively) with a power of
80% at a 1% level of significance.
Data were analysed by using Students t-test, MannWhitney U-test, and 2x2 2-test. Statistical calculations were performed using the Statistical Package for the Social Sciences (SPSS) (version 10.0.5, SPSS Inc., Chicago, IL, USA). P < 0.05 was considered statistically significant.
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Results |
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Prevalence of asthma in women with and without endometriosis
Asthma prevalence was similar in women with (23/467, 4.9%; 95% CI, 3.17.3) and without (22/412, 5.3%; 95% CI, 3.48.0; P = 0.781) endometriosis. No significant difference was observed in asthma prevalence among women with mild (rAFS stage III; 8/180, 4.4%) and severe (rAFS stage IIIIV; 15/287, 5.2%; P = 0.413) endometriosis.
Characteristics of asthma in women with and without endometriosis
Asthma severity was similar in women with and without endometriosis, with 12 (52.2%) women with endometriosis and 13 (59.1%) controls being in the intermittent (mildest) degree of severity (Table II). No significant difference was observed in the LWAQ total score between women with and without endometriosis. Interestingly women with endometriosis had higher score than controls in the construct avoidance; in addition there was a trend for women with endometriosis to have higher score than controls in the construct preoccupation, but neither difference was statistically significant (Table III).
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Discussion |
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The strengths of the current study consist in the fact that the diagnosis of asthma was based on internationally accepted criteria (American Thoracic Society, 1987). In addition, subjects included in the study and control groups were similar for the majority of demographic characteristics and health behaviours. Although there is evidence that obesity and overweight are associated with the development of asthma (Schaub and von Mutius, 2005
), it seems unlikely that the difference in BMI observed between women with and without endometriosis could have artificially masked the difference in asthma prevalence between study and control groups. This study was further strengthened by a power calculation demonstrating that the sample size was adequate to detect the difference in asthma prevalence between women with and without endometriosis observed by Sinaii et al.(Sinaii et al., 2002
) with a power of 80% at a 1% level of significance. Finally, asthma prevalence observed in our control group is similar to that previously reported by other studies (Ownby et al., 1996
; Adams et al., 1999
; Kwon et al., 2003
).
The findings of the current study are not completely unexpected. No obvious association can be seen between the factors involved in the pathogenesis of asthma and of endometriosis. In general, asthma can be subdivided into three forms: the extrinsic/allergic asthma, which is clearly caused by an allergen; the intrinsic/non-allergic asthma, which is not linked to such an allergen; and the mixed form. In 40% of young adults, asthma is associated with atopy manifesting through immunoglobulin E-dependent mechanisms (Bukantz and Lockey, 1993
) which do not seem to play a major role in the pathogenesis of endometriosis. Interleukin-4, which does not seem to be relevant in endometriosis (Gazvani et al., 2001
), mediates important pro-inflammatory functions in asthma, including T helper cell type 2 lymphocyte differentiation, induction of IgE production, up-regulation of IgE receptors, expression of vascular cell-adhesion molecule 1, promotion of eosinophil transmigration into the lungs, inhibition of T-lymphocyte apoptosis, and mucus hypersecretion (Kips, 2001
; Corry and Kheradmand, 2002
; Steinke, 2004
). In subjects without history of atopy, asthma (intrinsic non-allergic asthma) is thought to represent a form of autoimmunity, or autoallergy, triggered by viral or bacterial infections. It is known that there is an increased presence of specific tissue macrophage subtypes in the mucosal tissue of non-allergic versus allergic asthmatic patients (Bentley et al., 1992
). Although macrophages have a pivotal role in the development of endometriosis (Seli and Arici, 2003
), this observation does not seem to justify an increased prevalence of asthma in women with endometriosis.
In conclusion, the current study demonstrates that women with endometriosis do not have a higher risk of having asthma than other subjects. Future investigations should evaluate whether women with endometriosis are at increased risk of developing other co-morbidities.
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Acknowledgements |
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References |
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Submitted on May 26, 2005; resubmitted on July 14, 2005; accepted on July 18, 2005.
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