Asthma in women with endometriosis

S. Ferrero1,4, P. Petrera1, B.M. Colombo2, R. Navaratnarajah3, M. Parisi1, P. Anserini1, V. Remorgida1 and N. Ragni1

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


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
INTRODUCTION: This study aimed to investigate asthma prevalence and severity in women with and without endometriosis. METHODS: Before laparoscopy, asthma prevalence was evaluated in 879 women of reproductive age, undergoing surgery because of benign gynaecological conditions. Diagnosis of bronchial asthma was based on the American Thoracic Society criteria; asthma severity was classified in four categories according to the 2002 Global Initiative for Asthma guidelines. Asthmatic patients completed the Living with Asthma Questionnaire (LWAQ). Endometriosis was confirmed histologically and classified according to the revised American Fertility Society criteria. RESULTS: There were no significant differences in age, smoking status, and other demographic and health characteristics between patients with endometriosis (n = 467) and controls (n = 412). Asthma prevalence was similar in women with (23/467, 4.9%; 95% CI, 3.1–7.3) and without (22/412, 5.3%; 95% CI, 3.4–8.0; P = 0.781) 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. No significant difference was observed between women with and without endometriosis in the LWAQ total score. CONCLUSIONS: Women with endometriosis do not have an increased risk of having asthma.

Key words: asthma/endometriosis/quality of life


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Asthma is a chronic inflammatory disorder of the airways producing episodes of wheezing, chest tightness, shortness of breath, and coughing. Epidemiological data on asthma prevalence, morbidity and severity seem to point to a sex difference in the risk of having asthma. Women aged >20 years seem to have higher prevalence and morbidity rates of asthma than do males (Skobeloff et al., 1992Go). Several hypotheses about the different susceptibilities to asthma of men and women have been raised (Redline and Gold, 1994Go). Hormonal status has been invoked as one of the factors most likely to be able to differentially influence the risk of asthma occurrence (Venn et al., 1998Go); sex differences in the airway size have been suggested as a potential alternative explanation (Redline and Gold, 1994Go).

A recent cross-sectional survey conducted in the USA by the Endometriosis Association (Sinaii et al., 2002Go) 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, Sjogren’s 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, 2005Go).

The current prospective study aims to investigate asthma prevalence and severity in women with and without endometriosis undergoing surgery at our Institution.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
This study included women of reproductive age undergoing surgery at our Institution because of uterine myomas, ovarian cysts, pelvic pain, dysmenorrhoea, or infertility between June 2001 and December 2004. All consecutive women scheduled for surgery because of benign gynaecological conditions and examined during the pre-operative clinic by three investigators (F.S., P.P., R.V.) were asked to participate in the current study.

Diagnosis of bronchial asthma was based on the American Thoracic Society (1987)Go 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, 2002Go). 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, 1991Go; Hyland et al., 1991Go, 1994Go; Hyland and Crocker, 1995Go; Rutten-van Molken et al., 1995Go). 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, 1991Go; Hyland et al., 1991Go).

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)Go (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)Go. 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 Student’s t-test, Mann–Whitney U-test, and 2x2 {chi}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.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Characteristics of the study population
Out of 958 women approached for the study, 879 patients gave their consent to participate in the study, yielding a response rate of 91.8%; accordingly, the final study population included 467 women with endometriosis and 412 controls. Table I shows the demographic characteristics and health behaviours of the study population.


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Table I. Demographic characteristics and health behaviours of the study population

 

Prevalence of asthma in women with and without endometriosis
Asthma prevalence was similar in women with (23/467, 4.9%; 95% CI, 3.1–7.3) and without (22/412, 5.3%; 95% CI, 3.4–8.0; P = 0.781) endometriosis. No significant difference was observed in asthma prevalence among women with mild (rAFS stage I–II; 8/180, 4.4%) and severe (rAFS stage III–IV; 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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Table II. Classification of asthma severity according to the 2002 Global Initiative for Asthma guidelines

 

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Table III. Living with Asthma Questionnaire in women with and without endometriosis

 


    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
The current study shows that women with endometriosis do not have an increased risk of having asthma. Furthermore, no significant difference was observed in asthma severity between women with and without endometriosis.

The strengths of the current study consist in the fact that the diagnosis of asthma was based on internationally accepted criteria (American Thoracic Society, 1987Go). 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, 2005Go), 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., 2002Go) 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., 1996Go; Adams et al., 1999Go; Kwon et al., 2003Go).

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, 1993Go) 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., 2001Go), 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, 2001Go; Corry and Kheradmand, 2002Go; Steinke, 2004Go). 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., 1992Go). Although macrophages have a pivotal role in the development of endometriosis (Seli and Arici, 2003Go), 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.


    Acknowledgements
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
We are grateful to Prof. Michael E.Hyland (University of Plymouth, UK) for giving us permission to use the Living with Asthma Questionnaire in the present study.


    References
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
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Submitted on May 26, 2005; resubmitted on July 14, 2005; accepted on July 18, 2005.





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