Asthmatic Women Research Articles

The relationship of asthma medication use to perinatal outcomes

Maternal asthma has been reported to increase the risk of preeclampsia, preterm deliveries, and lower-birth-weight infants, but the mechanisms of this effect are not defined. We sought to evaluate the relationship between the use of contemporary asthma medications and adverse perinatal outcomes. Asthmatic patients were recruited from the 16 centers of the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network from December 1994 through February 2000. Gestational medication use was determined on the basis of patient history at enrollment and at monthly visits during pregnancy. Perinatal data were obtained at postpartum chart reviews. Perinatal outcome variables included gestational hypertension, preterm births, low-birth-weight infants, small-for-gestational-age infants, and major malformations. The final cohort included 2123 asthmatic participants. No significant relationships were found between the use of inhaled beta-agonists (n=1828), inhaled corticosteroids (n=722), or theophylline (n=273) and adverse perinatal outcomes. After adjusting for demographic and asthma severity covariates, oral corticosteroid use was significantly associated with both preterm birth at less than 37 weeks' gestation (odds ratio, 1.54; 95% CI, 1.02-2.33) and low birth weight of less than 2500 g (odds ratio, 1.80; 95% CI, 1.13-2.88). Use of inhaled beta-agonists, inhaled steroids, and theophylline do not appear to increase perinatal risks in pregnant asthmatic women. The mechanism of the association between maternal oral corticosteroid use and prematurity remains to be determined.

Murphy et al. Maternal asthma is associated with reduced female fetal growth. Am J Respir Crit Care Med 2003;168:1317-23

A low birth weight is more common in babies born to mothers with active asthma during pregnancy. This study investigated the patterns of such low birth weight and possible underlying mechanisms in a group of women with active asthma who were not treated with inhaled or systemic steroids during pregnancy in comparison with a control group of pregnant women. In pregnant women with asthma, there was a significant reduction in birth weights in female babies, whereas male birth weights were unaffected. The presence of a female fetus in these asthmatic women was associated with significantly reduced placental levels of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity and fetal estriol. 11β-HSD2 normally metabolizes maternal cortisol in the placenta, reducing the amount of cortisol reaching the fetus. This may explain the somewhat higher cortisol levels in the cord blood of the female babies born to the asthmatic women. The authors concluded that in pregnancies complicated by asthma there are fetal sex–specific adverse effects on placental function and female fetal growth that possibly explain the lower birth weight in female babies. It would be interesting to compare these findings with those in pregnant women whose asthma was not active.

Use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth

Background Inhaled steroids are recommended for the treatment of persistent asthma during pregnancy, but their potential effects on intrauterine growth have been inadequately evaluated. Objective The purpose of this study was to evaluate the association between maternal use of specific inhaled steroids and inhaled steroid dose during pregnancy and the incidence of infants who are small for gestational age (SGA) and mean birth weight. Methods Pregnant asthmatic women being treated with inhaled steroids were enrolled in the study before delivery by their managing allergists. Information regarding the specific inhaled steroid and daily dose used, requirement for oral steroids, occurrence of acute asthmatic episodes, maternal race, birth weight, gestational age, and congenital malformations was obtained for each patient. SGA was defined through use of a published normative sample of American births. Results A total of 474 women were enrolled in the study; of the 451 enrolled participants whose pregnancy ended in a singleton live birth, 396 (88%) completed the study. The incidence of infants with low birth weight, preterm births, and congenital malformations in this cohort was not greater than expected in the general population. The incidence of SGA was 7.1% (95% CI, 5.0% to 10.1%). No significant relationships between specific inhaled steroid or dose of inhaled steroid used and either SGA or mean birth weight were observed. Conclusion These data suggest that the use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth and supports the recommendation that inhaled steroids should be used in the management of persistent asthma during pregnancy.

Cyclooxygenase-2 gene polymorphism G −765C and prostaglandin synthesis in patients with bronchial asthma

Rationale Promoter polymorphism of COX-2 gene (G −765C), recently described by Papafili et al., lowered transcriptional activity of the gene by 30% in cultured fibroblasts (Arterioscler Thromb Vasc Biol. 22; 2002; 1631). The goal of the study was to investigate the genetic association and function of the polymorphism in adult patients with bronchial asthma. Methods COX-2 promoter region for G −765C SNP was genotyped by PCR-based RFLP. Three groups were studied: 1) a random sample from Cracow (n=549;M/F=237/312); 2) Patients with Aspirin-induced asthma (AIA) (n=117;M/F=41/76); 3) Asthmatics tolerating aspirin (ATA) (n=217;M/F=73/144). We studied ex vivo production of prostaglandins (PGs) by monocytes isolated from blood of asthmatic patients with GG (n=6) and CC (n=9) genotypes. Results In asthmatic patients the −765C allele frequency was similar (AIA=0.16; ATA=0.186), to the controls (Con=0.16). All groups followed Hardy-Weinberg equilibrium. Variant allele homozygotes (CC) were detected only in asthmatic women (p=0.004). In controls, distribution of CC genotypes did not differ between men and women. The baseline monocyte PGs production was nearly tenfold higher in CC homozygotes than in GG group (p=0.0003). Response to stimulation with LPS gave similar increase of PGs in both groups. Conclusions We demonstrated a functional effect of COX-2 −765C homozygocity resulting in increased PGs production by monocytes. However, genetic association with COX-2 was detected only in women patients.

Near-fatal asthma related to menstruation

Background Menstruation has been suggested as a possible trigger of near-fatal asthma (NFA), but the evidence supporting this association remains weak. Objective We sought to assess the role of menstruation as a contributing factor in the development of NFA episodes in women of reproductive age. Methods Forty-four female patients of reproductive age with near-fatal attacks were enrolled in a multicenter study. Data on patient and clinical characteristics were collected. We also performed spirometric and allergy studies when the patients were in stable condition. Results Significantly more NFA episodes were observed on the first day of menstruation (11 [25%] patients) than on the remaining days (33 [75%] patients, P = .022), and patients who presented for care on the first day of menstruation used more inhaled salbutamol as rescue medication (9 [9.5] vs 1.8 [3.7] μg/d during the 7 days before the asthma exacerbation, P = .003). Conclusion Menstruation might act as a contributing factor in the development of NFA episodes in patients with unstable asthma. Specific recommendations should be included in educational programs, and the self-management plans of asthmatic women of reproductive age should include the systematic recording of their asthma symptoms and pulmonary function in the perimenstrual phase.

Update in the treatment of asthma during pregnancy.

Asthma is the most common potentially serious medical problem to complicate pregnancy. Recent reports suggest that 7 of every 100 pregnant women suffer from asthma during pregnancy. Asthmatic women have been shown to be at an increased risk of complications during pregnancy. This may be secondary to inadequately controlled asthma or perhaps the result of the effects of certain asthma medications taken during pregnancy. The choice to use a specific medication during pregnancy is based on available human and animal data. Much of the information currently available regarding the safety of various asthma medications during pregnancy comes from several large cohort studies. This article reviews the specific aspects of pharmacological therapy during pregnancy as provided in the recommendations of the joint ad hoc committee of the American College of Allergy Asthma and Immunology and the American College of Obstetricians and Gynecologists. This article presents practical strategies for the management of asthma in our pregnant patients.

Maternal Asthma and Risk of Preterm Delivery

Approximately 1% of pregnant women are asthmatic and the prevalence could be increasing, like it is in the general population. The authors used data from a nested case-control study to learn whether maternal asthma is associated with a greater risk of preterm labor and delivery. The study group included 312 women who delivered before 37 completed weeks gestation and, as a control group, 424 women who delivered a singleton infant at term. Women with a history of asthma were approximately twice as likely as others to have preterm delivery (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.01-4.09). A slightly stronger association (OR, 2.37; 95% CI, 1.15-4.88) was evident after adjusting for maternal age, race/ethnicity, parity, Medicaid payment status, and smoking during pregnancy. Asthma correlated with a greater than 2-fold increase in risk of both spontaneous and medically induced preterm delivery, but the association was statistically significant only for the latter. Maternal asthma was associated with both moderate (34-36 weeks) and very (before 34 weeks) preterm deliveries. These findings point to an increased risk of preterm delivery in asthmatic women.

P.2.027 The occurence of obsessive compulsive symptoms in clozapine treated schizophrenic patients: Relationship with other clinical features

Recent asthma guidelines endorse the safety of long-acting β2-agonists (LABAs) and of mild and moderate doses of inhaled corticosteroids (ICSs) when required to control asthma during pregnancy, yet do not state a preferred medication within each class.To estimate the relative perinatal safety with the use of salmeterol and formoterol (LABAs) and that of fluticasone and budesonide (ICSs) during pregnancy.A subcohort of pregnancies from asthmatic women was selected from health care administrative databases of Quebec, Canada. Low birth weight (LBW) was defined as weight less than 2,500 g, preterm birth (PB) as delivery before 37 weeks of gestation, and small for gestational age (SGA) as a birth weight below the 10th percentile. The effect of treatment with salmeterol vs formoterol and fluticasone vs budesonide on the outcomes was determined with generalized estimating equation models.The LABA and ICS subcohorts were composed of 547 (385 salmeterol and 162 formoterol users) and 3,798 (3,190 fluticasone and 608 budesonide users) pregnancies, respectively. No statistically significant differences were observed for LBW (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.44-1.88), PB (OR, 1.11; 95% CI, 0.56-2.23), and SGA (OR, 1.16; 95% CI, 0.67-2.02) newborns between women exposed to salmeterol vs formoterol or between women exposed to fluticasone vs budesonide (LBW: OR, 1.08; 95% CI, 0.76-1.52; PB: OR, 1.07; 95% CI, 0.78-1.49; and SGA, OR: 1.10; 95% CI, 0.85-1.44).This study does not provide evidence of greater perinatal safety for one LABA or one ICS over the other.

Regulation of Allergic Lung Inflammation in Rats: Interaction between Estradiol and Corticosterone

Objective: One third of asthmatic women report a decreased expiratory peak flow during menses. Since asthma is characterized by lung inflammation and bronchopulmonary hyperresponsiveness, we investigated the role played by estradiol in allergic lung inflammation. Methods: Cell migration to the lungs of allergic female rats subjected to oophorectomy (OVx) was compared to that in their sham-operated (sham) control counterparts. Seven days after OVx or sham operation, the rats were sensitized intraperitoneally with ovalbumin (OA, 1 mg/kg) suspended in aluminum hydroxide (day 0). At day 7, a subcutaneous booster of OA was performed and an aerosolized OA challenge was carried out at day 14. One day later (day 15), the rats were killed and cell counts were performed in bronchoalveolar lavages (BAL), in peripheral blood and in bone marrow lavages. Results: After the antigen challenge, OVx rats showed a significant decrease in cell migration to the lung as compared to sham-operated rats. Differential analyses of BAL revealed a reduced number of eosinophils, mononuclear cells and neutrophils. In contrast, in bone marrow as well as in the peripheral blood the numbers of eosinophils, mononuclear cells and neutrophils were increased relative to sham controls. Mast cell numbers were similar in both groups. The estradiol receptor antagonist tamoxifen decreased the allergic lung inflammation in intact rats down to levels similar to those found in untreated OVx rats. In contrast, 17β-estradiol replacement in OVx rats reestablished the allergic lung inflammation, as observed by an elevated number of eosinophils, mononuclear cells and neutrophils recovered in BAL. Similarly, an elevated number of inflammatory cells were quantified in BAL from allergic OVx rats when corticosterone effects were blocked with metyrapone or RU-486. Conclusion: Our results suggest that estradiol has proinflammatory actions on the allergic lung response, and these actions seem to be mediated, at least in part, by endogenous glucocorticoids.

Perimenstrual asthma: A syndrome without known cause or cure

Perimenstrual worsening of asthma has been documented in 30% to 40% of asthmatic women. This increase in symptoms has been backed up by increased health care use perimenstrually, as well as by cyclic variation in peak expiratory flows. The cause of perimenstrual asthma (PMA) remains unclear. Fluctuations in hormone levels, their ratios, or both are a plausible explanation but have not been demonstrated with any consistency. Influences of sex hormones on inflammation is an area of future research, as are hormone-induced changes in smooth muscle function and β-adrenergic receptors, prostaglandin levels, and fluid retention in the bronchial mucosa. In the light of the high prevalence of PMA, it is difficult to understand why there has been no randomized controlled trial of hormone therapy. Nevertheless, several case reports have suggested beneficial effects of estrogens, pro-gestins, and their combination. In light of these positive case reports, well-designed, double-blind studies of sufficient sample size should now be performed to give treatment of PMA an evidence base. (J Allergy Clin Immunol 2003;112:271-82.)

Association of hormone replacement therapy with bronchial hyper-responsiveness

Postmenopausal hormone replacement therapy (HRT) has been linked to asthma in women, however, with inconsistent conclusions. This study examined the association of HRT with bronchial hyper-responsiveness (BHR). Eighty-five postmenopausal women completed a women-specific questionnaire and underwent methacholine challenge testing according to the protocol of the European community respiratory health survey. Associations of HRT use with BHR (based on a 20% fall in FEV 1), mild BHR (10% fall in FEV 1) or dichotomized dose–response slopes were analyzed by logistic regression, controlling for age, education, smoking and overweight. The 27 HRT users were less likely to show BHR compared to the 58 non-users (11% vs. 41%), multiply adjusted odds ratio (95% confidence interval) 0.12 (0.03, 0.55). Results for dose–response slopes were similar, while mild BHR showed no association with HRT use. These results point to a relaxing effect of estrogens on bronchial smooth muscle.

Gastroesophageal reflux disease (GERD) and asthma in women

Gastroesophageal reflux disease (GERD) and asthma in women

Pregnancy and Birth Outcomes in Families with Asthma

Studies of maternal asthma in pregnancy have shown an increased risk of adverse neonatal and maternal outcomes such as preeclampsia, hypertension, cesarean delivery, prematurity, low birth weight, and perinatal/neonatal mortality. However, results are not consistent between studies. We studied the association between maternal asthma and various adverse neonatal and maternal outcomes and explored whether there is any evidence that pregnancy exacerbates maternal asthma. The data were collected as part of the Childhood Asthma Prevention Study. Pregnant women with asthma or women whose partners or other children had current symptoms of asthma were recruited at six Sydney hospitals. All women recruited were post 36 weeks gestation and were living within 30 km of the study recruitment center. Information about family history of asthma was collected using a questionnaire at 36 weeks gestation and subsequent information about antenatal and perinatal events was obtained from hospital records. Data from 611 pregnant women were available for analysis, 340 of whom had asthma. Hypertension was significantly more common in asthmatics than in nonasthmatics [OR = 2.16 (1.02–4.6), p<0.043]. The prevalence of gestational diabetes, labor complications, delivery complications, and adverse neonatal outcomes did not differ significantly between the groups. We also found that the course of maternal asthma usually remains unchanged during pregnancy, but that more severe asthma is likely to get worse. We have confirmed previous observations that women with asthma are at increased risk of hypertension in pregnancy, which is consistent with studies that show that pregnant asthmatic women have a slightly increased risk of preeclampsia. However, we did not find evidence of an increased risk of adverse perinatal outcomes.

Gender Differences in Health‐Related Quality of Life Among Patients with Asthma

This study has a twofold objective: 1) to explore to what extent suffering from asthma affects the HRQL of men and women differently at several stages of disease severity and 2) to analyze whether the informed poorer HRQL of asthmatic women is related to their higher scores on instruments measuring emotionally disordered symptoms. One hundred fifty‐one outpatient asthmatics (84 women and 67 men) completed the Spanish versions of the Asthma Quality of Life questionnaire (AQL), as well as anxiety and depression inventories. A full history, physical examination, and pulmonary function test were performed on all subjects. Patients were classified into one of four asthma severity categories following the criteria of the Global Initiative on Asthma (GINA). There were no gender differences in sociodemographic variables, asthma duration, GINA, FEV1 or dyspnea. However, women showed a poorer HRQL than men, as well as high degrees of anxiety and depression. When these data were reanalyzed taking into account the four groups of asthma severity, women only reported a poorer HRQL than men at the intermittent asthma level. The gender differences on depression and anxiety scores were maintained at the three lower severity levels, but not at the most severe asthma degree. When depression and anxiety scores were partialed out, the AQL scores maintained significant relationships with asthma severity, dyspnea, and FEV1, both in women and men. Therefore, only in men were there also relationships among AQL and sociodemographic data. The best predictor of the women's HRQL was the dyspnea score, whereas in men it was the asthma severity (GINA).

Specific sensitization to common allergens and pulmonary function in the European Community Respiratory Health Survey.

The role of atopy in the evolution to chronic obstructive disease remains controversial. We aimed to assess the association between individual sensitization to common allergens and lung function. We analysed data from 12,687 subjects aged 20 to 44 years, from 34 centres in 15 countries participating in the European Community Respiratory Health Survey (ECRHS). Participants performed a blood test, lung function test, methacholine challenge, and answered an administered questionnaire. The relationships between specific IgE, FEV1 and FEV1/FVC ratio were assessed for each study centre stratified by sex, followed by random effects meta-analysis. Asthmatics sensitized to house dust mite had a lower FEV1 (-119 mL in women and -112 mL in men) and FEV1/FVC ratio (-1.95%, and -2.48%) than asthmatics without sensitization. Asthmatics sensitized to cat had a lower FEV1 (statistically significant for women only) and a lower FEV1/FVC ratio. Asthmatic women sensitized to grass had a lower FEV1 and a lower ratio, and those sensitized to Cladosporium had a lower FEV1. A weak association was found with sensitization to cat and to Cladosporium among non-asthmatic women, which disappeared after adjusting for BHR. We conclude that atopy was related to a lower lung function, which was only apparent among asthmatics. This relationship was explained by specific sensitization to cat and to house dust mite, the latter being homogeneous across areas.

Influence of Gender and Inspiratory Muscle Training on the Perception of Dyspnea in Patients With Asthma

Men and women respond differently to asthma. Maximal inspiratory mouth pressure (P(Imax)), beta(2)-agonist consumption, and perception of dyspnea (POD) were measured in 22 women and 22 men with mild persistent-to-moderate asthma. Next, the women were randomized into two groups: those who received inspiratory muscle training and those who received sham training. The training ended when the P(Imax) of the training group was equal to that of the male subjects. POD was then measured once again. Baseline P(Imax) was significantly lower (p < 0.01) while POD and mean daily beta(2)-agonist consumption were significantly higher in the female subjects. P(Imax) reached the level of the male subjects at the end of the 20th week of training. The increase in the P(Imax) was associated with a statistically significant decrease in mean daily beta(2)-agonist use and in POD to a similar level as in male subjects. POD and mean daily beta(2)-agonist consumption in asthmatic women are significantly higher, and the P(Imax) significantly lower, than that of their male counterparts. When the P(Imax) of female subjects following training is equal to that in male subjects, the differences in POD and mean daily beta(2)-agonist consumption disappear.

Reduced 11β-Hydroxysteroid Dehydrogenase Type 2 Activity Is Associated with Decreased Birth Weight Centile in Pregnancies Complicated by Asthma

Pregnancies complicated by asthma are associated with an increased risk of low birth weight. Currently, the mechanisms causing this outcome are unknown. To investigate whether impaired placental function may be a determinant, we measured placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity, protein and mRNA, placental CRH mRNA, fetal cortisol, and fetal estriol concentrations at delivery. Asthmatic subjects were classified according to inhaled glucocorticoid intake during pregnancy and compared with a control nonasthmatic group. There was a 25% reduction in neonatal birth weight centile in asthmatic women who did not use inhaled glucocorticoid treatment. This was accompanied by significantly reduced placental 11beta-HSD2 activity, significantly increased fetal cortisol, and a trend toward increased placental CRH mRNA and reduced fetal estriol concentrations. The use of inhaled glucocorticoids for treatment was associated with birth weight centile, 11beta-HSD2 activity, CRH mRNA, fetal cortisol, and estriol concentrations similar to control levels. There was a significant inverse correlation between fetal cortisol and fetal estriol concentrations across all groups. These studies demonstrate that inhaled glucocorticoid intake for the treatment of asthma is associated with improved placental function and fetal outcome, suggesting that inflammatory factors associated with asthma may be detrimental to fetal growth and development in these pregnancies.

Obesity may increase the incidence of asthma in women but not in men: longitudinal observations from the Canadian National Population Health Surveys.

To investigate the possibility of gender specificity for the effect of body mass index (BMI) on development of asthma, the authors used the longitudinal data from the first and second cycles of the National Population Health Survey, conducted in Canada in 1994-1995 and 1996-1997, respectively. Data from 9,149 subjects (4,266 men and 4,883 women) aged 20-64 years who reported no asthma at baseline were used in this analysis. The 2-year cumulative incidence of asthma was estimated by using a bootstrap procedure to take sampling weights and design effects into account. During the 2-year study period, 1.6% of the men and 2.9% of the women developed asthma. Average changes in body weight and BMI over the 2-year observation period were relatively small and were not associated with asthma incidence. However, baseline BMI was a significant predictor for asthma incidence in women. The adjusted odds ratio for women whose baseline BMI was at least 30.0 kg/m(2) versus 20.0-24.9 kg/m(2) was 1.9 (95% confidence interval: 1.1, 3.4), whereas the corresponding odds ratio of 1.1 (95% confidence interval: 0.3, 3.6) for men was not significantly different from unity. The authors concluded that obesity was related to development of asthma in women but not in men.

Autoimmune and related diseases among women with endometriosis: a survey analysis

Objective: Some have hypothesized that women with endometriosis may have an altered immune system but few report the prevalence of autoimmune diseases and other conditions among women with endometriosis. We report the prevalence and association of autoimmune diseases, endocrine conditions, chronic fatigue syndrome (CFS), fibromyalgia (FM), allergies, and asthma in women with endometriosis.

Airway Inflammation in Premenstrual Asthma

Premenstrual asthma (PMA) is a clinical picture with worsening of asthmatic symptoms and pulmonary functions in the late luteal phase of the menstrual cycle. The aim of this study was to evaluate the inflammatory changes in asthmatic women who complain of PMA.Forty asthmatic women attending our outpatient clinic were questioned about worsening of their asthma before menstruation. Eleven women (aged 17–40) who complained of PMA participated in the study. Subjects were asked to record peak expiratory flow rates, symptom scores, and β-agonist use daily. After the first menses on the seventh day of their cycle, and before the onset of the next menstruation, on the 26±3rd day of the cycle, patients were evaluated with pulmonary function tests, methacholine challenge test, and fractionated exhaled nitric oxide (FeNO) levels. Eosinophils in peripheral blood and induced sputum were also evaluated.When comparing the two groups of results, the significant changes were in FeNO levels, day-time symptom scores, and eosinophils in induced sputum (29.25 ppb/9.16 ppb p<0.05, 1/0.45 p = 0.05, %6.63/%4.09 p<0.01, respectively, before and after menstruation).These results show that PMA is not only a clinical picture with a decrease in airway calibre that can be related to the regulation of 2 receptors, but also a complex state with worsening of airway inflammation.