Pregnant Asthmatics Research Articles

Increased Antibiotic Utilization among Pregnant Women with Asthma in a Medicaid Population

Antibiotics are the most commonly prescribed medication in the prenatal period and prenatal antibiotic exposure has been associated with risk of childhood asthma. The role of maternal asthma status in prenatal antibiotic utilization has yet to be determined. We investigated the association of maternal asthma status and prenatal antibiotic use in women enrolled in a state Medicaid program. Our outcome was prenatal antibiotics from prescription fill data. Maternal asthma status was defined by ICD-9 codes and asthma medication utilization. Using multivariable regression analysis, we determined the association of women’s asthma status with antibiotic fills adjusting for factors including mother’s age at delivery, parity, maternal race, maternal education, maternal smoking and GBS status. Among 84,214 pregnant women, 4.5 % had asthma. Overall, 64% received antibiotics during pregnancy: 82% among women with asthma, 63% among those without asthma. Women with asthma had a 2.5-fold increase in odds of ever being prescribed antibiotics compared to those without asthma (adjusted OR: 2.46, 95% CI: 2.26, 2.67). Among antibiotic users, women with asthma were also at increased odds of receiving greater number of courses of antibiotics (aOR: 1.89, 95% CI: 1.77, 2.02) and had earlier time to first antibiotic fill in pregnancy. Maternal asthma was associated with increased antibiotic utilization during pregnancy. Women with asthma had higher cumulative dose and received antibiotics earlier in pregnancy than women without asthma. Future assessment to determine whether pregnant asthmatics are at higher infection risk or antibiotics are being used to treat asthma exacerbations may inform clinical decision making.

Pregnancy Outcomes of Patients with Asthma under Omalizumab Treatment: Case Report of a Country based Experience on 22 Pregnancies and 23 Infants

A prospective multicenter study reported safety of omalizumab in pregnant asthmatics. However, real life data about the topic is scarce. Therefore, we aimed to report outcomes of pregnant patients with asthma under omalizumab treatment and their infants in our county. Patients with asthma who received omalizumab for at least 6 months and at least one dose during their pregnancy were retrospectively evaluated using a questionnaire regarding their demographic features, disease- and therapy-related parameters, and the health of their infants. 20 pregnant patients and their 23 infant’s data were analyzed. The mean delivery age was 31.8 ± 7.4 years. They received omalizumab for 28.9 ± 21.8 months. Eight (36.4%) patients showed exacerbation of the disease during pregnancy. Forced expiratory volume in 1 second (FEV1) and asthma control test (ACT) scores at the starting time of omalizumab administration, first month of the pregnancy, and after delivery were 71 ± 18%, 83.4 ± 10.5%, and 80.5 ± 13% (FEV1), and 11.9 ± 4.9, 20.2 ± 2.6, and 20.4 ± 2.2 (ACT), respectively. One patient gave birth to twin infants, two patients to two infants each, and 17 to one infant each. Infant exposure to omalizumab was only one dose (300 mg omalizumab) for the twins, the first trimester for one infant, second and third trimester for four infants, and during all pregnancy and breastfeeding periods for 16 infants. Three (13%) infants had low birth weight and five (21.7%) were born prematurely. No congenital anomalies were detected. Seven (30.4%) infants presented atopic diseases during their life. Omalizumab treatment during pregnancy seems to be safe for both patients and their infants.

Management of Asthma during Pregnancy: Optimizing Outcomes and Minimizing Risk.

Pregnancy may be complicated by new onset or preexisting asthma. This article reviews diagnosis and management of asthma in the pregnant patient. Special attention is paid to the challenges in diagnosis and management of this condition during pregnancy. Asthma is one of the most common potentially serious medical problems to complicate pregnancy, and asthma may adversely affect both maternal quality of life and perinatal outcomes. Asthma may adversely affect both maternal quality of life and, perinatal outcomes. Pregnant asthmatics have been shown to be at an increased risk of adverse perinatal outcomes. Optimal management of asthma during pregnancy is thus important for both mother and baby. This article provides an update on the available literature regarding the safety of commonly used asthma medications during pregnancy.

Pregnancy outcomes among women with asthma

Purpose: The purpose of this study is to examine the association between maternal asthma and pregnancy, delivery and neonatal outcomes.Materials and methods:We carried out a retrospective cohort study using the Health Care Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) database from 2003 to 2011. Among women who delivered during this time period, we compared pregnancy, delivery, and neonatal outcomes in asthmatics versus non-asthmatics. Multivariate logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals.Results: In a cohort of 7,772,999 pregnant women, 223,236 (2.9%) had asthma. The prevalence of asthma-complicated pregnancies rose over the study period from 1.9% in 2003 to 3.7% in 2011 (p < .001). Pregnant asthmatics had more pre-existing health conditions, such as diabetes, chronic hypertension, obesity, and thyroid disease, and were more likely to smoke. Even after adjustment for these comorbidities, and other covariates, within statistical models, asthma was found to be associated with greater risk of several pregnancy complications: gestational hypertension, preeclampsia, gestational diabetes, placenta previa, preterm premature rupture of membranes, placental abruption, chorioamnionitis, preterm delivery, postpartum hemorrhage, venous thromboembolism, caesarean section delivery, and maternal mortality. Neonates born to asthmatics had greater risk of being small for gestational age and for having congenital anomalies, and lower risk of intrauterine fetal death.Conclusions: Asthma is associated with an increase in adverse pregnancy, labor, and neonatal outcomes. Close surveillance of asthmatic patients during the prenatal period is warranted and care in a tertiary hospital is advised.

Use of the Control of Allergic Rhinitis and Asthma Test and pulmonary function tests to assess asthma control in pregnancy.

Asthma is one of the most prevalent chronic medical conditions to complicate pregnancy. Similarly, active management strategies that prioritise asthma control in this vulnerable population can have a far-reaching impact. To describe lung function parameters and results of the Control of Allergic Rhinitis and Asthma Test (CARAT) questionnaire in pregnant asthmatics and to analyse correlations between lung function tests and CARAT results. All pregnant asthmatics who performed spirometry and CARAT between September 2014 and August 2015 were included. A medical records review was performed and data regarding demographics, sensitisation and medical prescriptions were recorded. Control of asthma and rhinitis was defined by CARAT total score (CARAT (T))≥24; upper airways (U) control if CARAT (U)>8; lower airways (L) control if CARAT (L)>15. Forty-two pregnant asthmatics were included, with a median age (interquartile range)of 32 (27-34) years; all had a previous medical diagnosis of asthma and rhinitis, 76% were atopic, 94% sensitised to dust mites and 43% were polissensitised. More than 80% presented poor control (CARAT (T)<24) in the first assessment and 15% had a percentage forced expiratory volume in the first second <80%. There were significant negative correlations between CARAT (L) and CARAT (T) scores and step-up of controller medication, (correlation coefficients =-0.453 and -0.392, respectively). The use of tools such as spirometry and validated questionnaires to objectively assess asthma control during pregnancy should be routinely applied to assist in the management of these patients. These data reinforce the importance of close monitoring of pregnant asthmatics to achieve and maintain better disease control.

To Determine How Frequently Pregnant Asthmatics Are Sensitive to Food and Inhalation Allergens

To Determine How Frequently Pregnant Asthmatics Are Sensitive to Food and Inhalation Allergens

Measurement of exhaled nitric oxide concentration in asthma: a systematic review and economic evaluation of NIOX MINO, NIOX VERO and NObreath.

High fractions of exhaled nitric oxide (FeNO) in the breath of patients with symptoms of asthma are correlated with high levels of eosinophils and indicate that a patient is likely to respond to inhaled corticosteroids. This may have a role in the diagnosis and management of asthma. To assess the diagnostic accuracy, clinical effectiveness and cost-effectiveness of the hand-held electrochemical devices NIOX MINO(®) (Aerocrine, Solna, Sweden), NIOX VERO(®) (Aerocrine) and NObreath(®) (Bedfont Scientific, Maidstone, UK) for the diagnosis and management of asthma. Systematic searches were carried out between March 2013 and April 2013 from database inception. Databases searched included MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Science Citation Index Expanded and Conference Proceedings Citation Index - Science. Trial registers such as ClinicalTrials.gov and the metaRegister of Controlled Trials were also searched in March 2013. All searches were updated in September 2013. A rapid review was conducted to assess the equivalence of hand-held and chemiluminescent FeNO monitors. Systematic reviews of diagnostic accuracy and management efficacy were conducted. A systematic review of economic analyses was also conducted and two de novo health economic models were developed. All three reviews were undertaken according to robust high-quality methodology. The rapid review (27 studies) found varying levels of agreement between monitors (Bland-Altman 95% limits of agreement up to ±10 parts per billion), with better agreement at lower FeNO values. Correlation was good (generally r > 0.9). The diagnostic accuracy review identified 22 studies in adults (all ages) and four in children. No studies used NObreath or NIOX VERO and seven used NIOX MINO. Estimates of diagnostic accuracy varied widely. FeNO used in combination with another test altered diagnostic accuracy only slightly. High levels of heterogeneity precluded meta-analysis. Limited observations included that FeNO may be more reliable and useful as a rule-in than as a rule-out test; lower cut-off values in children and in smokers may be appropriate; and FeNO may be less reliable in the elderly. The management review identified five randomised controlled trials in adults, one in pregnant asthmatics and seven in children. Despite clinical heterogeneity, exacerbation rates were lower in all studies but not generally statistically significantly so. Effects on inhaled corticosteroid (ICS) use were inconsistent, possibly because of differences in management protocols, differential effectiveness in adults and children and differences in population severity. One UK diagnostic model and one management model were identified. Aerocrine also submitted diagnostic and management models. All had significant limitations including short time horizons and the selective use of efficacy evidence. The de novo diagnostic model suggested that the expected difference in quality-adjusted life-year (QALY) gains between diagnostic options is likely to be very small. Airway hyper-responsiveness by methacholine challenge test is expected to produce the greatest QALY gain but with an expected incremental cost-effectiveness ratio (ICER) compared with FeNO (NObreath) in combination with bronchodilator reversibility of £1.125M per QALY gained. All remaining options are expected to be dominated. The de novo management model indicates that the ICER of guidelines plus FeNO monitoring using NObreath compared with guidelines alone in children is expected to be approximately £45,200 per QALY gained. Within the adult subgroup, FeNO monitoring using NObreath compared with guidelines alone is expected to have an ICER of approximately £2100 per QALY gained. The results are particularly sensitive to assumptions regarding changes in ICS use over time, the number of nurse visits for FeNO monitoring and duration of effect. Limitations of the evidence base impose considerable uncertainty on all analyses. Equivalence of devices was assumed but not assured. Evidence for diagnosis is difficult to interpret in the context of inserting FeNO monitoring into a diagnostic pathway. Evidence for management is also inconclusive, but largely consistent with FeNO monitoring resulting in fewer exacerbations, with a small or zero reduction in ICS use in adults and a possible increased ICS use in children or patients with more severe asthma. It is unclear which specific management protocol is likely to be most effective. The economic analysis indicates that FeNO monitoring could have value in diagnostic and management settings. The diagnostic model indicates that FeNO monitoring plus bronchodilator reversibility dominates many other diagnostic tests. FeNO-guided management has the potential to be cost-effective, although this is largely dependent on the duration of effect. The conclusions drawn from both models require strong technical value judgements with respect to several aspects of the decision problem in which little or no empirical evidence exists. There are many potential directions for further work, including investigations into which management protocol is best and long-term follow-up in both diagnosis and management studies. This study is registered as PROSPERO CRD42013004149. The National Institute for Health Research Health Technology Assessment programme.

Management of Critical Asthma Syndrome During Pregnancy

One-third of pregnant asthmatics experience a worsening of their asthma that may progress to a critical asthma syndrome (CAS) that includes status asthmaticus (SA) and near-fatal asthma (NFA). Patients with severe asthma before pregnancy may experience more exacerbations, especially during late pregnancy. Prevention of the CAS includes excellent asthma control involving targeted early and regular medical care of the pregnant asthmatic, together with medication compliance. Spontaneous abortion risk is higher in pregnant women with uncontrolled asthma than in non-asthmatics. Should CAS occur during pregnancy, aggressive bronchodilator therapy, montelukast, and systemic corticosteroids can be used in the context of respiratory monitoring, preferably in an Intensive Care Unit (ICU). Systemic epinephrine should be avoided due to potential teratogenic side-effects and placental/uterine vasoconstriction. Non-invasive ventilation has been used in some cases. Intratracheal intubation can be hazardous and rapid-sequence intubation by an experienced physician is recommended. Mechanical ventilation parameters are adjusted based on changes to respiratory mechanics in the pregnant patient. An inhaled helium-oxygen gas admixture may promote laminar airflow and improve gas exchange. Permissive hypercapnea is controversial, but may be unavoidable. Sedation with propofol which itself has bronchodilating properties is preferred to benzodiazepines. Case reports delineating good outcomes for both mother and fetus despite intubation for SA suggest that multidisciplinary ICU care of the pregnant asthmatic with critical asthma are feasible especially if hypoxemia is avoided.

Alterations in inflammatory, antiviral and regulatory cytokine responses in peripheral blood mononuclear cells from pregnant women with asthma

Severe asthma exacerbations during pregnancy are a common complication leading to poor health outcomes for both the mother and the baby. Asthma exacerbations are caused most frequently by respiratory viruses. A balance between antiviral and inflammatory immune responses is critical during pregnancy; the balance may be altered by asthma and respiratory virus infection. Peripheral blood mononuclear cells (PBMCs) were isolated from (i) non-pregnant healthy controls, (ii) pregnant non-asthmatics, (iii) post-partum non-asthmatics, (iv) non-pregnant asthmatics (v) pregnant asthmatics, and (vi) post-partum asthmatics. Cells were cultured in vitro with the mitogen phytohaemagglutinin or with a strain of the 2009 pandemic swine influenza. Interferon (IFN)-γ, interleukin (IL)-10 and IL-17 protein were measured from culture supernatant. Neutrophil counts were obtained in samples from pregnant and post-partum women. Following the phytohaemagglutinin stimulation of PBMCs, pregnant asthmatics had significantly higher IL-17 and significantly lower IFN-γ responses compared with healthy non-pregnant women. Following infection with influenza, a significant reduction was also observed in IFN-γ and IL-10 production from PBMC of pregnant asthmatics. The IL-17 response to phytohaemagglutinin correlated with the neutrophil percentage. Differences in IFN-γ, IL-10 and IL-17 were found to persist for at least 6 months post-partum. A reduction in antiviral and regulatory immunity with increased inflammation during pregnancy occurs in PBMC from pregnant women with asthma. This novel information may relate to the increased susceptibility and disease severity to respiratory virus infections observed during pregnancy.

Fractioned exhaled nitric oxide (FENO) is not a sufficiently reliable test for monitoring asthma in pregnancy

It has been reported that fractioned exhaled nitric oxide (FENO) can be used for monitoring airway inflammation and for asthma management but conclusions drawn by different researchers are controversial.The aim of our study was to evaluate the clinical usefulness of FENO assessment for monitoring asthma during pregnancy.We monitored 72 pregnant asthmatics aged 18–38years (Me=29 years) who underwent monthly investigations including: the level of asthma control according to GINA (Global Initiative for Asthma), the occurrence of exacerbations, ACT (Asthma Control Test), as well as FENO and spirometry measurements. In 50 women, during all visits, asthma was well-controlled. In the remaining 22 women, asthma was periodically uncontrolled.FENO measured at the beginning of the study did not show significant correlation with retrospectively evaluated asthma severity (r=0.07; p=0.97). An analysis of data collected during all 254 visits showed that FENO correlated significantly but weakly with ACT scores (r=0.25; p=0.0004) and FEV1 (r=0.21; p=0.0014). FENO at consecutive visits in women with well-controlled asthma (N=50) showed large variability expressed by median coefficient of variation (CV)=32.0% (Min 2.4%, Max 121.9%). This concerned both: atopic and nonatopic groups (35.5%; and 26.7%, respectively). Large FENO variability (35.5%) was also found in a subgroup of women (N=11) with ACT=25 constantly throughout the study. FENO measured at visits when women temporarily lost control of asthma (N=22; 38 visits), showed an increasing tendency (64.2ppb; 9.5ppb–188.3ppb), but did not differ significantly (p=0.13) from measurements taken at visits during which asthma was well-controlled (27.6ppb; 6.2ppb–103.4ppb). The comparison of FENO in consecutive months of pregnancy in women who had well-controlled asthma did not show significant differences in FENO values during the time of observation. The assessment of asthma during pregnancy by means of monitoring FENO is of limited practical value due to this parameter’s considerable intrasubject variability, regardless of the degree of asthma control.

The Long-Term Variability of FeNO in Pregnant Asthmatic Women with Controlled Asthma

Introduction: Fractional exhaled nitric oxide (FeNO) is considered a useful, noninvasive marker of airway inflammation in asthma and allergic rhinitis. It has also been suggested that anti-inflammatory treatment guided by monitoring of exhaled NO could improve overall asthma control. However, long-term intrasubject variability of this parameter as well as the rate of its change, which can be considered clinically significant, have not been established yet. The aim of our study was to assess the long-term variability of FeNO in pregnant asthmatic women with controlled asthma. Material and methods: Pregnant, non-smoking women with asthma were recruited at between 3 and 6 months of gestation. Exhaled nitric oxide (FeNO) spirometric parameters were measured, and asthma control tests (ACT) were completed at monthly visits up to delivery. The data of 26 subjects with well controlled asthma during pregnancy (ACT values within the range 20–25, normal spirometric parameters, stable treatment) were analysed. The variability of FeNO values was assessed using the variation coefficient CV (standard deviation × 100%/arithmetic mean). Results: The median level of FeNO coefficient of variation (CV) was: 33.8% (range 11.3 to 121.9) in all subjects with well controlled asthma during pregnancy. There were no statistically significant differences in FeNO variability between groups of patients who had at least one measurement of FeNO higher than 50 ppb (39%; 11.8–121.9%) and those with all FeNO values below 50 ppb (29.9%; 11.3–71.8%), as well as between atopic (35.7%; 11.8–121.9%) and nonatopic (24.2%; 11.3–71.8%) pregnant asthmatics (p = 0.95 and 0.11, respectively). Conclusions: High long-term variability of fractional exhaled nitric oxide values revealed in pregnant women with well controlled asthma indicates that changes in this parameter should be interpreted with caution when used for asthma treatment monitoring.

A Longitudinal Study of Knowledge, Attitudes and Self-Efficacy in Pregnant Asthmatics

The objectives of this study of pregnant women with asthma are 1) to describe their knowledge and attitudes of asthma in pregnancy and their self-efficacy in carrying out their self-management plan during pregnancy, 2) to determine if their knowledge, attitudes, and self-efficacy changed as their pregnancy progressed, and 3) to ascertain the relationship between knowledge, attitudes, and self-esteem and age, education, trimester of pregnancy, weeks of pregnancy, the number of times pregnant and live births. Sixty-eight pregnant women who had an asthma diagnosis were given knowledge, attitudes and self-efficacy questionnaires initially during the point of first contact (first or second) trimester (Time I) and subsequently during the latter part of their pregnancy (third trimester) (Time II). A demographic data form was also administered at Times I and II. Data were collected in an urban academic medical clinic and analyzed using SPSS 17. Data analysis utilized frequencies, paired samples t tests, and linear regression. There were no significant differences between Time I and Time II in attitudes and self-efficacy. Significant differences were limited to the knowledge questionnaire (t = 4.370, p = 0.05). There was a significant relationship between education and knowledge. Pregnant women with asthma had gaps in their knowledge of asthma in pregnancy, although their knowledge increased as their pregnancy progressed from Time I to Time II. Also, the more education the women had, the better they understood asthma. Education for pregnant women with asthma is tailored to their needs and modified as necessary. Nurses are prepared to address this challenge.

Asthma and Pregnancy

Asthma is a chronic inflammatory condition affecting up to 10% of all women of child-bearing age. In most patients asthma can be safely treated during pregnancy. However, asthma crises or exacerbations during pregnancy can be life threatening to both the mother and the child. Uncontrolled asthma has been associated with adverse pregnancy outcomes and adverse effects to the fetus (eg, prematurity, low birth weight, increased risk of congenital malformations). Impaired oxygenation during asthma crisis in pregnancy is a major concern. Aggressive treatment of asthma during pregnancy, including the use of systemic corticosteroids if necessary, has been advocated to achieve asthma control and to avoid attacks. Pregnant asthmatics require regular and intensified monitoring. National and international guidelines recommend that antiasthmatic treatment should be maintained and intensified if necessary for the well-being of both the mother and the unborn child. Although there is consensus that the potential risks of uncontrolled asthma during pregnancy outweigh the potential risks of antiasthmatic medications the use of the lowest doses possible to achieve and maintain asthma control is recommended.

Impaired type I and III interferon response to rhinovirus infection during pregnancy and asthma

BackgroundAcute respiratory tract infections are common ailments to all individuals and the human rhinoviruses (HRVs) cause most of these infections. Pregnant women have increased susceptibility and disease severity to viral...

Habitual Snoring and Asthma Comorbidity Among Pregnant Women

Background. Obstructive sleep apnea (OSA) or habitual snoring and asthma are known comorbid conditions in men and non-pregnant women. This comorbidity has not been evaluated among pregnant women. We assessed the habitual snoring–asthma relationship among pregnant women. Methods. A cohort of women (N = 1335) were interviewed during pregnancy, and we ascertained participants' asthma status and collected information about habitual snoring, before and during pregnancy. Logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results. Compared with non-asthmatics, the adjusted OR among asthmatics for snoring before pregnancy was 2.13 (95% CI 1.10–4.12). The odds of snoring during early pregnancy was 1.79-fold (OR = 1.79; 95% C; 1.07–3.01). Associations were more pronounced among overweight (≥25 kg/m2) asthmatics (OR = 5.39; 95% CI 2.27–12.75). Conclusions. We report a cross-sectional association of habitual snoring and asthma among pregnant women. If confirmed, pregnant asthmatics may benefit from more vigilant screening and management of OSA or habitual snoring during pregnancy.

Increased circulating heat shock protein 70 levels in pregnant asthmatics

Asthma is one of the most common diseases complicating pregnancy and represents a risk factor for several maternal and perinatal complications. The natural history of asthma is known to change in pregnancy, but very few data are available in the terms of pathomechanism of this change during gestation. Circulating heat shock protein 70 (Hsp70) levels are decreased in healthy pregnancy, which might reflect physiological immunotolerance. The aim of our study was to determine the serum levels of Hsp70 in asthmatic women during gestation. Forty pregnant women with bronchial asthma and 40 healthy pregnant women matched for maternal and gestational age were involved in this case-control study. Serum Hsp70 levels were measured using the ELISA Kit of R&D Systems. Spirometry and oxygen saturation measurements were performed in asthmatic patients. In asthmatic pregnant women, an increase of serum Hsp70 levels was observed compared to healthy pregnant women (median (25-75 percentile): 0.44 ng/ml (0.36-0.53) versus 0.21 ng/ml (0-0.27), p < 0.001). Fetal birth weight of asthmatic mothers was significantly smaller than of healthy controls, but in the normal range (3,230 g (2,690-3,550) versus 3,550 g (3,450-3,775), p < 0.05). A statistically significant negative correlation between maternal age and serum Hsp70 concentrations (Spearman R = -0.48, p = 0.0018) and a significant positive correlation between gestational age and serum Hsp70 levels (Spearman R = 0.83, p < 0.001) were detected in healthy pregnant women. In conclusion, this study proves an elevation of circulating Hsp70 levels during asthmatic pregnancy compared to healthy pregnant women. However, further studies are warranted to determine the role of circulating Hsp70 in the pathogenesis of maternal and perinatal complications of asthma in pregnancy.

Surface markers of lymphocyte activation in pregnant asthmatics

ProblemPregnancy-associated immunologic alterations may improve the course of asthma. Severe maternal asthma with an exacerbation impairs fetal growth.Method of studyLymphocyte activation was estimated by flow cytometry analysis of surface markers in non-pregnant healthy and mild or moderate persistent asthmatic women and healthy as well as mild or moderate persistent asthmatic, third trimester pregnant women.ResultsCompared with non-pregnant healthy subjects (n = 12) activated pools within CD4 and CD8 T cells were larger and the number of NK T cells were increased both in non-pregnant asthmatic (n = 12) and in healthy pregnant (n = 13) subjects (all p < 0.05). No further lymphocyte activation was observed in pregnant asthmatics (n = 21) compared either with non-pregnant asthmatic, or pregnant healthy women. Average birth weight of newborns was lower (p < 0.05) in the asthmatic than in the healthy pregnant group.ConclusionPregnancy is a state of wide-spread lymphocyte activation but it may blunt lymphocyte activation which characterizes bronchial asthma.

T‐helper type 2 polarization among asthmatics during and following pregnancy

Asthma is the most common medical condition during pregnancy. While increased production of T helper cytokines has been reported to occur in both asthma and pregnancy, the effect of T-helper type 2 (Th2) polarization on asthma symptoms during pregnancy has not been well-characterized. We hypothesized that systemic Th2 cytokine and chemokine polarization occurs among asthmatics to a greater extent during their pregnancy, and is associated with more severe asthma and increased Th2 polarization in the newborn. Fifty-six pregnant asthmatics were recruited from prenatal clinics affiliated with New York Presbyterian Hospital. Systemic production of interleukin-4, interferon-gamma, eotaxin and IP10 were measured by intracytoplasmic staining or ELISA at recruitment, peripartum and post-partum, and in the cord blood. The frequency of asthma symptoms was measured by questionnaires and compared with Th biomarkers. The chemokine ratio (IP10/eotaxin) declined over the course of pregnancy (from 3.3 +/- 1.3 to 1.4 +/- 0.2, P = 0.016), but IP10 and eotaxin increased post-partum. The decrease in the chemokine ratio was associated with more frequent asthma symptoms. A non-significant trend towards decreased interferon-gamma and increased interleukin-4 production was detected. Cord blood eotaxin levels correlated with maternal levels (r = 0.35, P = 0.03). Other peripartum biomarkers were not associated with Th2 polarization nor with subsequent respiratory symptoms in the newborn. IP10/eotaxin declined over the course of pregnancy and was associated with worse asthma symptoms. Alterations of Th1/Th2 chemokine balance during pregnancy may identify women prone to more severe asthma during pregnancy.

Catalytic Hydrolysis of VIP in Pregnant Women with Asthma

Rationale: The neuropeptide vasoactive intestinal peptide (VIP) is one of the physiologic mediators of non-adrenergic, non-cholinergic smooth muscle relaxation of the airway and an important modulator of innate and adaptive immune responses. VIP catalytic autoantibodies are increased in asthma and serum VIP level is decreased during acute exacerbation of asthma. The effect of pregnancy on asthma is variable and depends in part on the severity of pre-existing asthma, along with other physiological and pathophysiological changes. We hypothesized that hydrolysis of VIP by circulating catalytic VIP antibodies will be increased in pregnancy in patients with asthma. Study objective: To determine the level of catalytic autoantibodies to VIP in pregnant asthmatics compared to non-pregnant asthmatics and control pregnant women without asthma. Methods: We prospectively enrolled eight pregnant asthmatics (age, 26.5 ± 2.6 years; mean ± SEM), nine pregnant women without asthma (32.0 ± 3.0 years), seven non-pregnant women with asthma (25.0 ±1.9 years), and seven non-pregnant women without asthma (34.4 ± 2 years) into the study. VIP hydrolysis was performed in all subjects. Results: Immunoglobulin G (IgG) autoantibodies that catalyze the hydrolysis of vasoactive intestinal peptide (VIP) were present at greater levels in the blood of pregnant women with asthma (7.6 ± 1.1 pM VIP/6 h) compared to pregnant women without asthma (4.0 ± 0.5; p < 0.001), non-pregnant asthmatics (4.9 ± 0.9; p < 0.05) or non-pregnant women without asthma (1.9 ± 0.7; p < 0.05). Conclusion: An increase in the VIP hydrolyzing activity of IgG is independently associated with asthma and pregnancy. The autoantibodies hold the potential of affecting the pathophysiology of the airways in pregnant asthmatics.

Increased interferon‐γ‐ and interleukin‐4‐synthesizing subsets of circulating T lymphocytes in pregnant asthmatics

Pregnancy frequently interferes with the course of bronchial asthma, and asthmatic pregnant women experience less successful pregnancies. T lymphocytes synthesizing IL-4 or IFN-gamma are important in allergic mechanisms of the airways as well as in materno-fetal immunity. We hypothesized that pregnancy (a T helper-2 polarized state) of asthmatics will enhance the number of circulating T2 lymphocytes, but decrease the subset-producing IFN-gamma (T1 lymphocytes) and thereby cause a culminating T2 dominance with possible clinical consequences. IL-4- or IFN-gamma-producing T lymphocytes were determined by flow cytometry in healthy (n=8) and asthmatic (n=13) non-pregnant women and healthy (n=18) and asthmatic (n=48) pregnant women of similar chronological and gestational (2nd-3rd trimester) age and asthma severity (Global Initiative for Asthma II-III). In the blood of non-pregnant women--healthy or asthmatic--the numbers of IL-4- and IFN-gamma+ T cells were very low (<10/microL blood). In contrast, in asthmatic pregnant women, the cell counts were 182+/-27 and 39+/-6 for IFN-gamma+ and IL-4+ T cells/microL blood, respectively (both P<0.05 vs. respective control values of non-pregnant asthmatics). Within the asthmatic pregnant group, significant negative correlations were revealed between the numbers of IFN-gamma+ or IL-4+ T cells and maternal peak expiratory flow as well as birth weight of newborns (both P<0.05). These data show a previously unknown immunological interference between asthma and pregnancy. The culminating proliferation of IFN-gamma+ and IL-4+ T lymphocytes may potentially impair maternal airway symptoms as well as fetal development.