Dr Megan Jensen

Physiologic changes during pregnancy have implications for both upper and lower airway function. Upper airway resistance increases, and total lung capacity decreases. Upper airway symptoms increase; some women develop pregnancy-induced rhinitis and there is an increased prevalence of sleep-disordered breathing compared to prepregnancy. Longitudinal studies examining changes in upper and lower airway function parameters are limited, particularly in women with asthma. Some studies have observed reduced lung function with advancing gestation; however, changes are small and unlikely to be of major clinical significance. Spirometry is therefore a useful tool for clinical assessment of women with asthma during pregnancy.

Background: Asthma affects 12.7% of pregnant women in Australia. Key recommendations for asthma management during pregnancy include: 4¿6 weekly review of lung function, medications, written asthma action plan, inhaler device technique, current asthma control and triggers; smoking cessation and vaccination advice. It is unknown if these key recommendations are provided to pregnant women with asthma in Australia. Aim: To explore usual antenatal asthma management (usual care) in Australia and the inclusion of key recommendations. Method: Pregnant women with asthma were invited to complete an online survey distributed in 2 antenatal clinics and via social media platforms from July 2017-Jan 2019. Results: The survey was completed by 142 pregnant women with asthma. 87(61%) were enrolled in an asthma management clinical trial and were therefore not receiving ¿usual¿ care. Data presented is from 55(39%) women receiving usual care at survey completion. Of these women, 36% did not have their asthma reviewed during their pregnancy, 31% had a written asthma action plan, 11% had lung function assessed, 38% had an asthma medication review and 35% had their inhaler technique reviewed. 65% were not questioned about their asthma symptoms, 85% were not asked about asthma triggers, 96% were not given information about vaccinations and 95% did not receive smoking cessation information. Conclusions: Overall, the key recommendations for antenatal asthma management were not always provided for this sample of pregnant women receiving usual care. Improved knowledge and implementation of these key recommendations by health professionals may alter this situation and improve maternal and infant outcomes.

Background: Little is known about the physical and mental health impact of exposure to landscape fire smoke in women with asthma. This study examined the health impacts and information-seeking behaviours of women with asthma exposed to the 2019/2020 Australian fires, including women who were pregnant. Methods: Women with asthma were recruited from the Breathing for Life Trial in Australia. Following the landscape fire exposure period, self-reported data were collected regarding symptoms (respiratory and non-respiratory), asthma exacerbations, wellbeing, quality of life, information seeking, and landscape fire smoke exposure mitigation strategies. Participants¿ primary residential location and fixed site monitoring was used to geolocate and estimate exposure to landscape fire-related fine Particulate Matter (PM2.5). Results: The survey was completed by 81 pregnant, 70 breastfeeding and 232 non-pregnant and non-breastfeeding women with asthma. Participants had a median daily average of 17 µg/m3 PM2.5 and 105 µg/m3 peak PM2.5 exposure over the fire period (October 2019 to February 2020). Over 80% of participants reported non-respiratory and respiratory symptoms during the fire period and 41% reported persistent symptoms. Over 82% reported asthma symptoms and exacerbations of asthma during the fire period. Half the participants sought advice from a health professional for their symptoms. Most (97%) kept windows/doors shut when inside and 94% stayed indoors to minimise exposure to landscape fire smoke. Over two in five (43%) participants reported that their capacity to participate in usual activities was reduced due to prolonged smoke exposure during the fire period. Participants reported greater anxiety during the fire period than after the fire period (mean (SD) = 53(13) versus 39 (13); p < 0.001). Two in five (38%) pregnant participants reported having concerns about the effect of fire events on their pregnancy. Conclusion: Prolonged landscape fire smoke exposure during the 2019/2020 Australian fire period had a significant impact on the health and wellbeing of women with asthma, including pregnant women with asthma. This was despite most women taking actions to minimise exposure to landscape fire smoke. Effective and consistent public health messaging is needed during landscape fire events to guard the health of women with asthma.

Objective: Guidelines for asthma management contain a consensus recommendation that inhaled corticosteroid (ICS) dose should not be stepped down in pregnancy. However, this is not consistent with consumer preferences and pharmacological principles to minimize medication exposure during pregnancy. We investigated exacerbations after changes to ICS and long acting beta agonist (LABA) therapy in pregnant women with asthma. Methods: Pregnant women (n = 220) were recruited to a randomized controlled trial (RCT) where maintenance treatment was adjusted monthly based on either symptoms (control group), or fractional exhaled nitric oxide (FeNO, to alter ICS) and symptoms (to alter LABA, FeNO group). Exacerbations were monitored prospectively. Results: ICS were used by 137 (62.3%) women at some time during pregnancy. ICS dose remained unchanged in 16 women (11.7%, 95% confidence interval [CI] 7¿18%), increased in 37 women (27%, 95%CI 20¿35%), decreased in 34 women (24.8%, 95%CI 18%¿33%), or both increased and decreased in 50 women (36.5%, 95%CI 29¿45%). Exacerbations occurred within 14 days of ICS step-down in 11 women (13%, 95%CI 7.5%¿22%). This was not significantly different from exacerbations occurring within 14 days of step-up, in 7 women (8.1%, 95%CI 4%¿16%, P = 0.294). There were no differences between management groups. Exacerbations occurred within 14 days of step-down in 14.7% (95%CI 7%¿30%) of women in the control group, and in 12% (95%CI 6%¿24%) of women in the FENO group. Conclusions: ICS step-down could be considered when eosinophilic inflammation or symptoms are low, and may be a useful management approach for women, doctors, and midwives wishing to minimize ICS exposure during pregnancy.

Asthma and gestational diabetes mellitus are prevalent during pregnancy and associated with adverse perinatal outcomes. The risk of gestational diabetes mellitus is increased with asthma, and more severe asthma; yet, the underlying mechanisms are unknown. This review examines existing literature to explore possible links. Asthma and gestational diabetes mellitus are associated with obesity, excess gestational weight gain, altered adipokine levels and low vitamin D levels; yet, it¿s unclear if these underpin the gestational diabetes mellitus¿asthma association. Active antenatal asthma management reportedly mitigates asthma-associated gestational diabetes mellitus risk. However, mechanistic studies are lacking. Existing research suggests asthma management during pregnancy influences gestational diabetes mellitus risk; this may have important implications for future antenatal strategies to improve maternal-fetal outcomes by addressing both conditions. Addressing shared risk factors, as part of antenatal care, may also improve outcomes. Finally, mechanistic studies, to establish the underlying pathophysiology linking asthma and gestational diabetes mellitus, could uncover new treatment approaches to optimise maternal and child health outcomes.

Background: Spirometry is commonly used to assess and monitor lung function. It may also be a useful tool to monitor maternal health during pregnancy. However, large studies examining lung function across gestation are limited. Also, whether spirometry values follow the same pattern during pregnancy in women with and without asthma is unknown. Objective: To investigate the effect of advancing gestation, and its interaction with asthma, on lung function in a large well-defined cohort of pregnant women. Methods: Data were obtained from prospective cohorts involving women with (n = 770) and without (n = 259) asthma (2004-2017), recruited between 12 and 22 weeks' gestation. Lung function (forced vital capacity [FVC], FEV1, FEV1:FVC%) was assessed periodically during pregnancy using spirometry. Multilevel mixed-effect regression models were used to assess changes in lung function over gestation. Results: Asthma had a significant effect on baseline lung function (FEV1%, -9%; FVC%, -3%; FEV1:FVC%, -4%). FVC% decreased with advancing gestation (-0.07%/wk; 95% CI, -0.10 to -0.04]), as did FEV1%, but only among those without asthma (women without asthma: -0.14%/wk, 95% CI, -0.22 to -0.06%; compared with women with asthma: 0.02%/wk, 95% CI, -0.01 to 0.06). FEV1:FVC% remained relatively stable for women without asthma (0.03%/wk; 95% CI, -0.08 to 0.02), but increased for women with asthma (0.06%/wk; 95% CI, 0.04 to 0.16). Conclusions: Data suggest that advancing gestation negatively affects FVC% and FEV1%. This is consistent with extrapulmonary restriction from advancing pregnancy. Yet, the presence of asthma altered the trajectories of FEV1% and FEV1:FVC%. Optimal asthma management during pregnancy might have opposed the negative effects of gestation on lung function.

Low 25-hydroxyvitamin D (25(OH)D) levels are common in pregnancy and associated with adverse maternal/neonatal outcomes. In pregnant women with asthma, this study examined the association of lifestyle-and asthma-related factors on 25(OH)D levels and maternal/neonatal outcomes by vitamin D status. Serum 25(OH)D was measured at 16 and 35 weeks gestation in women with asthma (n = 103). Body mass index (BMI), gestational weight gain (GWG), smoking status, inhaled corticosteroid (ICS) use, asthma control, airway inflammation, and exacerbations, and maternal/neonatal outcomes were collected. Baseline and change (¿) in 25(OH)D were modelled separately using backward stepwise regression, adjusted for season and ethnicity. Maternal/neonatal outcomes were compared between low (25(OH)D < 75 nmol/L at both time points) and high (=75 nmol/L at one or both time points) vitamin D status. Fifty-six percent of women had low vitamin D status. Obesity was significantly associated with lower baseline 25(OH)D (Adj-R2 = 0.126, p = 0.008); ICS and airway inflammation were not. Excess GWG and season of baseline sample collection were significantly associated with ¿25(OH)D (Adj-R2 = 0.405, p < 0.0001); asthma-related variables were excluded (p > 0.2). Preeclampsia was more common in the low (8.6%) vs. high (0%) vitamin D group (p < 0.05). Obesity and excess GWG may be associated with gestational 25(OH)D levels, highlighting the importance of antenatal weight management.

Maternal asthma increases the risk of infant wheeze. Breastfeeding may offer protection but there is limited evidence in this high-risk group. We examined associations between breastfeeding and respiratory outcomes, in infants born to women with asthma. This study was a secondary analysis of two prospective cohorts of pregnant women with asthma, and their infants, conducted between 2007 and 2018. At 6 ± 1 (T1) and 12 ± 1 (T2) months post-partum, mothers reported breastfeeding patterns and infant wheeze (primary outcome), bronchiolitis, and related medication use and healthcare utilization, via a validated questionnaire; a subgroup completed face-to-face interviews. ¿2 tests and logistic regression models, adjusting for confounders, were utilized. Data were complete for 605 participants at T1 and 486 (80%) at T2. Of 605 participants: 89% initiated breastfeeding and 38% breastfed for more than 6 months. Breastfeeding for more than 6 months vs ¿never¿ was associated with a reduced adjusted relative risk of infant wheeze at T1 (0.54, 95% confidence interval, 0.30-0.96). Bronchiolitis risk was reduced at T1 and T2 with more tha 6 months of breastfeeding vs ¿never.¿ Breastfeeding duration of 1 to 3 months, 4 to 6 months, and more than 6 months were associated with a reduced risk of infant healthcare utilization (all P <.05, vs ¿never¿), but not medication use (P >.05). Breastfeeding for more than 6 months was associated with a reduced risk of wheeze, bronchiolitis, and wheeze-related healthcare utilization in infants at risk due to maternal asthma. Notably, breastfeeding for shorter durations was associated with a reduced risk of healthcare utilization compared with none. Larger cohorts are needed to further examine the impact of breastfeeding exposure on respiratory health in infants exposed to maternal asthma.

Background: The use of fractional exhaled nitric oxide (FeNO)-based asthma management during pregnancy can significantly reduce asthma exacerbations in non-smoking pregnant women. The feasibility of implementing this strategy into antenatal care has not been explored. Aims: To examine the feasibility of implementing FeNO-based asthma management into antenatal clinics in New South Wales (NSW) Australia. Materials and Methods: Semi-structured face-to-face interviews with video elicitation were conducted with healthcare professionals (HCPs) providing antenatal care in one of two hospital-based antenatal clinics in NSW, Australia. The video shown demonstrated the use of the FeNO instrument and other aspects of the management strategy, in antenatal care. Interviews were recorded, transcribed and analysed using qualitative content analysis. Results: A total of 20 interviews were conducted with 15 midwives, four obstetricians, and one general practitioner. Two main themes and ten sub-themes arose: Getting a number (sub-themes: engaging, technically easy, objective, predictive, reassuring); and Resourcing (sub-themes: time and timing, systems, staff, education and cost). Comments included: ¿It's easy, fast and effective¿ and ¿the main barrier is time¿. All HCPs felt capable of facilitating the FeNO-based management strategy, with appropriate education, and were willing to undertake this strategy, saying: ¿¿it would be perfectly acceptable for a midwife or doctor to do it¿; also, ¿they don't necessarily need to see a physician, it's something that midwives would take on generally¿¿. Conclusion: Participants in this study considered FeNO-based asthma management for pregnant women to be a feasible addition to antenatal care following appropriate provision of resources and education.

Background: Asthma affects approximately 12.7% of pregnant women in Australia. Increased maternal and infant morbidity is closely associated with poorly controlled asthma during pregnancy. Midwives are well placed to provide antenatal asthma management but data on current asthma management during pregnancy is not available, nor is the use of guidelines for clinical practice by this health professional group. Aim: To explore self-reported antenatal asthma management provided by midwives across Australia and how this reflects guideline recommendations. Method: An online survey was developed and distributed throughout Australia via the Australian College of Midwives, social media and healthcare facilities. Results: Responses from 371 midwives were obtained. Ten percent of midwives rated their knowledge as ¿good¿ and 1% as ¿very good¿, with 39% ¿poor¿ or ¿very poor¿. Being ¿somewhat¿ or ¿not at all¿ confident to provide antenatal asthma management was noted by 87% of midwives. Clinical guidelines were referred to by 50% of midwives and 40% stated that their main role was to refer women to other healthcare professionals. Only 54% reported that a clear referral pathway existed. Most respondents (>90%) recognised key recommendations for asthma management such as smoking cessation, appropriate vaccinations, and the continuation of prescribed asthma medications. Conclusion: Although midwives appear aware of key clinical recommendations for optimal antenatal asthma management, low referral to clinical practice guidelines and lack of knowledge and confidence was evident. Further research is required to determine what care pregnant women with asthma are actually receiving and identify strategies to improve antenatal asthma management by midwives.

Measurement of vitamin D status has significant use in clinical and research settings, including during pregnancy. We aimed to assess the agreement of total 25-hydroxyvitamin D (25(OH)D) concentration, and its three analytes (25-hydroxyvitamin D3 (25(OH)D3 ), 25-hydroxyvitamin D2 (25(OH)D2 ) and Epi-25-hydroxyvitamin D3 (Epi-25(OH)D3 )), in plasma and serum samples collected during pregnancy, and to examine the proportion of women who change vitamin D status category based on sample type. Matching samples were collected from n = 114 non-fasting women between 12¿25 weeks gestation in a clinical trial in Newcastle, Australia. Samples were analysed by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) to quantify total 25(OH)D and its analytes and examined using Bland-Altman plots, Pearson correlation (r), intraclass correlation coefficient and Cohen¿s Kappa test. Serum total 25(OH)D ranged from 33.8¿169.8 nmol/L and plasma ranged from 28.6¿211.2 nmol/L. There was a significant difference for total 25(OH)D based on sample type (measurement bias 7.63 nmol/L for serum vs plasma (95% Confidence Interval (CI) 5.36, 9.90, p = 0.001). The mean difference between serum and plasma concentrations was statistically significant for 25(OH)D3 (7.38 nmol/L; 95% CI 5.28, 9.48, p = 0.001) and Epi-25(OH)D3 (0.39 nmol/L; 95% CI 0.14, 0.64, p = 0.014). Of 114 participants, 28% were classified as vitamin D deficient (<50 nmol/L) or insufficient (<75 nmol/L) based on plasma sample and 36% based on serum sample. Nineteen (16.7%) participants changed vitamin D status category based on sample type. 25-hydroxyvitamin D quantification using LC-MS/MS methodology differed significantly between serum and plasma, yielding a higher value in plasma; this influenced vitamin D status based on accepted cut-points, which may have implications in clinical and research settings.

Background: Maternal asthma is associated with perinatal complications and respiratory illness in offspring. Obesity increases asthma exacerbation risk in pregnancy and risk of wheeze in offspring. Objectives: In this secondary analysis of a randomized controlled trial, we investigated the influence of maternal body mass index, gestational weight gain (GWG), and fractional exhaled nitric oxide (FENO)-based management on asthma exacerbations in pregnancy and offspring wheeze. Methods: A total of 220 women were randomized to asthma treatment adjustment according to symptoms (control group), or FENO and symptoms (FENO group). Exacerbations were recorded prospectively. Height and weight were measured at baseline, and in late pregnancy. GWG was categorized according to Institute of Medicine guidelines. A validated parent-completed questionnaire assessed infant wheeze-related outcomes. Results: FENO-based management was associated with a significantly lower incidence rate ratio for maternal exacerbations in nonobese mothers (0.52, 95% confidence interval [CI], 0.31-0.88, P = .015, n = 129), and women with GWG within recommendations (0.35, 95% CI, 0.12-0.96, P = .042, n = 43), but not for obese mothers (0.59, 95% CI, 0.32-1.08, P = .089, n = 88), or women with excess GWG (0.58, 95% CI, 0.32-1.04, P = .07, n = 104). Recurrent bronchiolitis occurred in 5.3% (n = 1) of infants born to non-overweight mothers, 16.7% (n = 3) of infants of overweight mothers, and 21.7% (n = 5) of infants of obese mothers in the control group. In the FENO group, 2 infants of obese mothers had recurrent bronchiolitis (7.1%, P = .031). Conclusions: The benefits of FENO-based management are attenuated among obese mothers and those with excess GWG, indicating the importance of weight management in contributing to improved asthma management in pregnancy.

Background: Studies demonstrate the prescription rate for inhaled corticosteroids (ICS) decreases in early pregnancy, possibly increasing exacerbation risk. This could be related to non-adherence to prescribed asthma medication or medication cessation by the patient or doctor. ICS use during pregnancy has not previously been summarized in a systematic review. Objective: The aim of this systematic review and meta-analysis was to evaluate the use of ICS during pregnancy among asthmatic women, specifically: (1) the prevalence of use, (2) changes of use during pregnancy compared with pre-pregnancy and (3) medication adherence among ICS users. Methods: We systematically searched literature in Embase, MEDLINE, CINAL and Cochrane, using terms related to asthma, pregnancy and medication use. All English articles reporting ICS among pregnant women with asthma were included. Prevalence, changes in ICS use during pregnancy and ICS adherence were pooled using STATA (version 15.0, StataCorp USA). Results: A total of 4237 references were retrieved in the initial search. Screening and review led to the inclusion of 52 articles for one or more aims (Aim 1: N¿=¿45; Aim 2, N¿=¿13; and Aim 3, N¿=¿5). The pooled prevalence of ICS use during pregnancy was 41% (95%CI 36%-45%); 49% (95%CI 44%-55%) in Europe, 39% (95%CI 32%-47%) in Australia and 34% (95%CI 27%-41%) in North America. In eight prescription databases, ICS prescription rates lowered in the first trimester of pregnancy, compared with pre-pregnancy, increased in the second trimester and decreased in the third trimester. Five studies reported ICS adherence among pregnant women, using four measures of self-reported non-adherence. In two comparable studies, pooled ICS non-adherence was 40% (95%CI 36%-44%). Conclusions: The prevalence of ICS use among pregnant women with asthma is 41% and varies widely between countries and continents, and prescription rates for ICS change throughout pregnancy. More studies are needed to investigate ICS adherence during pregnancy in women with asthma.

Background: Vitamin D may influence pregnancy and infant outcomes, especially infant respiratory health. This study aimed to examine vitamin D status in pregnant women with asthma, and whether higher vitamin D levels are associated with fewer adverse respiratory outcomes in their infants. Methods: Pregnant women with asthma, recruited from John Hunter Hospital Newcastle Australia (latitude 33°S), had serum total 25-hydroxyvitamin-D (25(OH)D) measured at 16 and 35 weeks gestation. Infant respiratory outcomes were collected at 12 months by parent-report questionnaire. Mother¿infant dyads were grouped by serum 25(OH)D during pregnancy: 25(OH)D < 75 nmol/L (at both time-points) versus 25(OH)D = 75 nmol/L (at one or both time-points). Results: In 52 pregnant women with asthma, mean serum 25(OH)D levels were 61 (range 26¿110) nmol/L at 16 weeks, and 65 (range 32¿116) nmol/L at 35 weeks, gestation. Thirty-one (60%) women had 25(OH)D < 75 nmol/L at both time-points; 21 (40%) had 25(OH)D = 75 nmol/L at one or both time-points. Maternal 25(OH)D < 75 nmol/L during pregnancy was associated with a higher proportion of infants with ¿wheeze ever¿ at 12 months, compared with 25(OH)D = 75 nmol/L (71 versus 43%, p =.04). Infant acute-care presentations (45 versus 13%, p =.02) and oral corticosteroid use (26 versus 4%, p =.03) due to ¿asthma/wheezing¿ were higher in the maternal group with 25(OH)D < 75 nmol/L, versus =75 nmol/L. Conclusions: Most pregnant women with asthma had low vitamin D status, which persisted across gestation. Low maternal vitamin D status was associated with greater risk of adverse respiratory outcomes in their infants, a group at high risk of developing childhood asthma.

Background: Asthma affects 12.7% of pregnancies in Australia. Poorly controlled asthma is associated with increased maternal and infant morbidity and mortality. Optimal antenatal management of asthma during pregnancy has the potential to reduce complications relating to asthma. Evidence-based clinical practice guidelines help to translate health research findings into practice and when implemented can improve health outcomes. National and International guidelines currently provide recommendations for optimal asthma care in pregnancy. Aim: To appraise the existing asthma in pregnancy guidelines with respect to their evidence for recommendations, consistency of recommendations and appropriateness for clinical practice. Method: The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to appraise four English language asthma in pregnancy guidelines, published or updated between 2007 and 2016. The recommendations, range and level of evidence was analysed. Results: Two of the four guidelines scored highly in most domains of the appraisal. Many of the recommendations made in the appraised guidelines were consistent. Due to the lack of randomised controlled trials involving pregnant women with asthma, most recommendations were evidenced by consensus and expert opinion rather than high quality meta-analysis, systematic reviews of randomised controlled trials. Conclusion: The recommended antenatal asthma management was generally consistent among the guidelines but lacked clarity in some areas which then leave them open to interpretation. More randomised controlled trials involving pregnant women with asthma are required to fortify the recommendations made and asthma management guidelines should be included in Australian Antenatal Care Guidelines as they currently are not.

Background: Prebiotic soluble fibers are fermented by beneficial bacteria in the colon to produce short-chain fatty acids (SCFAs), which are proposed to have systemic anti-inflammatory effects. Objective: This review examines the effect of SCFAs, prebiotics, and pre- and probiotic combinations (synbiotics) on systemic inflammation. Design: Relevant English language studies from 1947 to May 2017 were identified with the use of online databases. Studies were considered eligible if they examined the effects of SCFAs, prebiotics, or synbiotics; were delivered orally, intravenously, or per rectum; were on biomarkers of systemic inflammation in humans; and performed meta-analysis where possible. Results: Sixty-eight studies were included. Fourteen of 29 prebiotic studies and 13 of 26 synbiotic studies reported a significant decrease in =1 marker of systemic inflammation. Eight studies compared prebiotic and synbiotic supplementation, 2 of which reported a decrease in inflammation with synbiotics only, with 1 reporting a greater anti-inflammatory effect with synbiotics than with prebiotics alone. Meta-analyses indicated that prebiotics reduce C-reactive protein (CRP) [standardized mean difference (SMD): -0.60; 95% CI: -0.98, -0.23], and synbiotics reduce CRP (SMD: -0.40; 95% CI: -0.73, -0.06) and tumor necrosis factor-a (SMD -0.90; 95% CI: -1.50, -0.30). Conclusions: There is significant heterogeneity of outcomes in studies examining the effect of prebiotics and synbiotics on systemic inflammation. Approximately 50% of included studies reported a decrease in =1 inflammatory biomarker. The inconsistency in reported outcomes may be due to heterogeneity in study design, supplement formulation, dosage, duration, and subject population. Nonetheless, meta-analyses provide evidence to support the systemic anti-inflammatory effects of prebiotic and synbiotic supplementation.

Background Obesity is a risk factor for exacerbations of asthma, but the mechanisms of this effect in pregnancy are unknown. Objective This study determined the influence of maternal body mass index, gestational weight gain, eosinophilic inflammation, and systemic macrophage activation on the risk of exacerbations during pregnancy. Methods Women with asthma (n = 164) participated in the study. Body mass index recorded at baseline (17 weeks gestation) was categorized as healthy weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (>30 kg/m2). Exacerbations requiring medical intervention were recorded prospectively. Asthma control, medication use, and fractional exhaled nitric oxide were assessed monthly; additional visits occurred during exacerbations. Peripheral blood was collected at baseline for the measurement of eosinophils, soluble CD-163, C-reactive protein, and IL-6. Results Exacerbations occurred in a higher proportion of overweight (51.1%) and obese (48.4%) women compared with healthy weight women (25%; P =.026). Excess weight gain during pregnancy was not associated with exacerbation risk. Macrophage activation (elevated serum soluble CD-163) was associated with exacerbations requiring oral corticosteroids (P =.043), whereas high peripheral blood eosinophils or fractional exhaled nitric oxide were not associated with exacerbation or oral corticosteroid use. Conclusions Being overweight or obese confers a greater risk of asthma exacerbation during pregnancy, and may be due to systemic macrophage activation.

Background Few instruments exist to ascertain the severity of a preschool-aged child's asthma exacerbations managed at home. Objective We sought to develop and validate a functional status instrument to assess asthma exacerbation severity in preschoolers. Methods The parent-completed Asthma Flare-up Diary for Young Children (ADYC), which was developed systematically, comprises 17 items, each scored from 1 (best) to 7 (worst). The ADYC was completed daily from the onset of an upper respiratory tract infection (URTI) until asthma symptom resolution; the cumulative daily score was reported. The ADYC was examined for key psychometric properties in a randomized placebo-controlled trial of pre-emptive high-dose fluticasone in preschoolers with URTI-induced asthma. Results In 121 children aged 2.7 ± 1.1 years (59.5% male), the ADYC's internal consistency (Cronbach a =.97), feasibility (97% completion), and test-retest reliability (r = 0.71; 95% CI, 0.59-0.80) were demonstrated. The ADYC was responsive to change between 2 consecutive days (Guyatt statistic = 0.77) with a minimal important difference of 0.22 (0.17-0.27). Of 871 episodes, the cumulative ADYC score was significantly higher during exacerbations than during URTIs (mean difference [MD], 7.6; 95% CI, 6.4-8.9) and for exacerbations with an acute-care visit (MD, 9.1; 95% CI, 7.6-10.7), systemic corticosteroids (MD, 10.1; 95% CI, 8.3-12.0), and hospitalization (MD, 6.8; 95% CI, 2.9-10.7) versus those without. In children receiving fluticasone, the ADYC score was significantly lower versus that in the placebo group (MD, 5.1; 95% CI, 1.8-8.3). Conclusions The 17-item ADYC proved feasible, responsive to day-to-day changes, and discriminative across exacerbations of different severities. In a trial testing effective therapy in preschoolers, it identified a significant reduction in asthma exacerbation severity.

Background Few instruments exist to measure caregivers' functional status during a young child's asthma exacerbation. Objective We sought to develop and validate a measure of caregivers' functional status during a preschooler's asthma exacerbation. Methods The psychometric properties of the 21-item questionnaire Effects of a Young Child's Asthma Flare-up on the Parents (ECAP) were tested in a randomized placebo-controlled trial of pre-emptive high-dose fluticasone in preschoolers with virus-induced asthma. Caregivers completed the ECAP questionnaire on the last day their child exhibited symptoms of an upper respiratory tract infection or asthma exacerbation (episode). The mean of each item, scored on a scale of 1 (best) to 7 (worst), provided the ECAP score. Results Ninety-three preschoolers (2.5 ± 1.0 years old; 62.4% male) experienced 878 episodes. Feasibility (80% questionnaire return rate; 90% completion) and internal consistency (Cronbach a = 0.97) were high. Of 628 episodes with a completed ECAP questionnaire, 621 (98.9%) had data on exacerbations, and 609 (97.0%) had data on health care use. The ECAP score was significantly higher for children experiencing an asthma exacerbation versus those who were not (mean difference, 0.8; 95% CI, 0.6-1.0) and for episodes resulting versus not resulting in an emergency visit (mean difference, 1.2; 95% CI, 1.0-1.4), systemic corticosteroid use (mean difference, 1.4; 95% CI, 1.1-1.7), or hospitalization (mean difference, 1.9; 95% CI, 1.4-2.5). The ECAP score was significantly lower in children treated with fluticasone versus those treated with placebo (mean difference, -0.7; 95% CI, -1.1 to -0.3). Conclusions The 21-item ECAP questionnaire, showing high feasibility, internal consistency, discriminative validity, and responsiveness, has the psychometric properties to serve as a validated outcome to measure the burden of preschoolers' asthma exacerbations on their caregivers' functional status.

Studies have identified prenatal flavour exposure as a determinant of taste preferences in infants; however, these studies have focused on relatively small samples and limited flavours. As many parents struggle with getting children to accept a variety of nutritious foods, a study of the factors influencing food acceptance is warranted. The objective of this study was to determine whether exposure to a wider variety of fruit and vegetables and overall higher diet quality in utero results in acceptance of a greater variety of these foods and better diet quality for offspring during childhood. This study is a secondary data analysis of pregnant women (n = 52) and their resulting offspring recruited for the Women and Their Children's Health study in NSW, Australia. Dietary intake of mothers and children was measured using food frequency questionnaires. Diet quality and vegetable and fruit variety were calculated using the Australian Recommended Food Score and the Australian Child and Adolescent Recommended Food Score. Associations between maternal and child diet quality and variety were assessed using Pearson's correlations and the total effect of in utero maternal pregnancy diet on childhood diet was decomposed into direct and indirect effect using mediation analysis. Maternal pregnancy and post-natal diet were both correlated with child diet for overall diet quality and fruit and vegetable variety (P < 0.001). Mediation analyses showed that the indirect effect of maternal pregnancy diet on child diet was mediated through maternal post-natal diet, particularly for fruit (P = 0.045) and vegetables (P = 0.055). Nutrition intervention should therefore be aimed at improving diet quality and variety in mothers with young children, in order to subsequently improve eating habits of offspring.

Background: Venous blood is the usual sample for measuring various biomarkers, including 25-hydroxyvitamin D (25OHD). However, it can prove challenging in infants and young children. Hence the finger-prick capillary collection is an alternative, being a relatively simple procedure perceived to be less invasive. We elected to validate the use of capillary blood sampling for 25OHD quantification by liquid chromatography tandem-mass spectrometry (LC/MS-MS). Methods: Venous and capillary blood samples were simultaneously collected from 15 preschool-aged children with asthma 10 days after receiving 100,000 IU of vitamin-D3 or placebo and 20 apparently healthy adult volunteers. 25OHD was measured by an in-house LC/MS-MS method. Results: The venous 25OHD values varied between 23 and 255 nmol/l. The venous and capillary blood total 25OHD concentrations highly correlated (r2 = 0.9963). The mean difference (bias) of capillary blood 25OHD compared to venous blood was 2.0 (95% CI: -7.5, 11.5) nmol/l. Conclusion: Our study demonstrates excellent agreement with no evidence of a clinically important bias between venous and capillary serum 25OHD concentrations measured by LC/MS-MS over a wide range of values. Under those conditions, capillary blood is therefore adequate for the measurement of 25OHD.

Obese asthma is characterised by infiltration of adipose tissue by activated macrophages and mast cells. The aim of this study was to examine the age and sex effects of immunometabolism in obese asthma. Obese and non-obese asthmatic children and adults underwent spirometry, body composition assessment by dual energy X-ray absorptiometry and measurement of serum soluble CD163 (sCD163), tryptase, C-reactive protein (CRP) and other adipocytokines. Plasma CRP (p<0.01) and leptin (p<0.01) were elevated in obese asthmatic adults, and sCD163 (p=0.003) was elevated in obese asthmatic children. We observed significantly higher sCD163 in obese female children compared to obese female adults and male children, and higher CRP in obese female adults compared to obese male children and adults. Serum tryptase concentrations were not significantly different across age groups. sCD163 positively correlated with the proportion of android fat in obese female children (r=0.70, p=0.003) and obese female adults (r=0.65, p=0.003). In obese female children, sCD163 was inversely associated with forced expiratory volume in 1 s % predicted (r=-0.55, p=0.02) and was positively associated with the Asthma Control Questionnaire (r=0.57, p=0.02). Obese children with asthma have sex-specific macrophage activation, which may contribute to worse asthma control and lung function. The heterogeneous systemic inflammatory profile across age and sex suggests the existence of sub-phenotypes in obese asthma at the molecular level.

Background Previous research has demonstrated that plasma carotenoids are a reliable biomarker of usual fruit and vegetable intake. The review aims were to synthesize (i) the mean dietary intake and (ii) plasma concentrations of carotenoids reported from validation studies (iii) compare the strength of the relationship between the two, measured using different dietary assessment methods. Methods Six databases were used to locate studies that included: adult populations, assessment of dietary intake, measurement of plasma carotenoids and reported the comparison between the two measures. Results One hundred and forty-two studies were included with 95,480 participants, the majority of studies were cross-sectional (n = 86), with randomized controlled trials (RCTs) (n = 18), 14 case-control studies and 13 cohorts. The most common reported dietary carotenoid and plasma carotenoid was lycopene: weighted dietary mean intake (4555.4 ug/day), and plasma concentration 0.62 umol/L (95% CI: 0.61, 0.63, n = 56studies. The strongest weighted correlation between the two measures was found for cryptoxanthin (r = 0.38, 95% CI 0.34, 0.42) followed by a-carotene (r = 0.34, 95% CI 0.31, 0.37). Conclusion This review summarizes typical dietary intakes and plasma concentrations and their expected associations based on validation studies conducted to date which provides a benchmark for future validation studies.

Background:Whether body composition is associated with lung function in asthmatic children has not been investigated. This study aimed to primarily investigate whether BMI z-score and body composition were associated with respiratory function in asthmatic children.Methods:In a cross-sectional study, male (n = 27; mean age: 11.9 y (SD: 2.3)) and female (n = 21; mean age: 13.6 y (SD: 2.2)) asthmatic children underwent clinical assessment.Results:BMI z-score was associated with forced expiratory volume in 1 s (FEV 1; r = 0.458), forced vital capacity (FVC; r = 0.477), and total lung capacity (TLC; r = 0.451) in males only (P < 0.05). Total lean mass was associated with FEV 1 (r = 0.655), FVC (r = 0.562), and TLC (r = 0.635) in males, as was thoracic lean mass (FEV 1 (r = 0.573), FVC (r = 0.526), and TLC (r = 0.497); P < 0.05). TLC was associated with total (r = 0.522) and thoracic (r = 0.532) lean mass in females (P < 0.05). Fat mass was not associated with lung function in this group.Conclusion:Lean mass, not fat mass, is associated with lung function in children with asthma. The positive association between BMI z-score and respiratory function in male children is driven by lean mass. Although body weight can be easily monitored in the clinical setting, body composition can provide important information. Future research exploring lean mass and lung function associations could inform future interventions. Copyright © 2014 International Pediatric Research Foundation, Inc.

Asthma is a chronic inflammatory disorder of the airways. The inflammatory response in asthma is heterogeneous. Allergen specific responses lead to activation of the acquired immune system, via a predominantly IL-5 mediated, eosinophilic pathway. Stimuli such as viruses and bacteria activate the innate immune system, via a predominantly IL-8 mediated, neutrophilic pathway. Asthma has also been demonstrated to involve a systemic inflammatory component. Glucocorticoids are the predominant pharmacological treatment used to control inflammation in asthma. However, compliance with medications can be compromised due to patient concerns about side effects. Hence dietary interventions that target the inflammatory response in asthma have great potential. Various aspects of dietary intake are known to modulate inflammation. Saturated fatty acids can induce an inflammatory response via activation of pattern recognition receptors. Omega-3 fatty acids can be anti-inflammatory, via mechanisms such as modification of eicosanoid production. Antioxidants can have anti-inflammatory effects as they scavenge free radicals, preventing activation of transcription factors including NF-¿B. Chronic excess energy intake can lead to obesity, which augments inflammation due to the release of inflammatory mediators by adipose tissue. Here we review the role of these dietary components in asthma. © 2014 Bentham Science Publishers.

Background: Obese men are more likely to have poor dietary patterns compared to women, increasing diet-related chronic disease risk. The impact of a male-only weight loss intervention on dietary intakes is under-evaluated. The aim was to deter-mine whether overweight/obese men randomised to self-help paper-based resources with or without online support, achieved greater improvements in diet compared with Wait-list controls at 3 and 6 months following a gender tailored weight-loss intervention.