Background: Severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) are important complications of severe asthma. The evidence for treating them with omalizumab is limited. Objective: To determine the effectiveness of treatment with omalizumab in severe allergic asthma patients comparing those with and without evidence of fungal sensitisation using data recorded in the Australian Xolair registry. Methods: Data from the Australian Xolair Registry (AXR) was analysed to determine change in Asthma Control Questionnaire (ACQ-5) score, exacerbation frequency, and oral corticosteroid (OCS) dosage over a 24 month period of omalizumab treatment. Patients were grouped into cohorts based on fungal sensitisation, and an analysis of improvement in outcomes between baseline and 24 months was conducted within each group. A further subgroup analysis of patients with ABPA was also conducted. Results: SAFS and non-fungal sensitized (NFS) both demonstrated significant improvements in ACQ-5, exacerbations and reduced regular oral corticosteroid dose over the 24-month period of omalizumab treatment. After adjusting for age, sex, BMI, smoking history, visit and baseline FEV1% predicted there was no significant difference in improvements between the two cohorts. A subgroup analysis of ABPA patients similarly demonstrated significant improvement on omalizumab. Conclusion: Omalizumab is an effective therapy in SAFS, leading to sustained improvements in symptoms and exacerbations for 24 months. Omalizumab seems to provide significant benefit in ABPA.

Background: Improved diagnostic tools for predicting future exacerbation frequency in asthmatic patients are required. A sputum gene expression signature of 6 biomarkers (6-gene signature [6GS], including Charcot-Leyden crystal galectin [CLC]; carboxypeptidase 3 [CPA3]; deoxyribonuclease 1-like 3 [DNASE1L3]; alkaline phosphatase, liver/bone/kidney [ALPL]; CXCR2; and IL1B) predicts inflammatory and treatment response phenotypes in patients with stable asthma. Recently, we demonstrated that azithromycin (AZM) add-on treatment in patients with uncontrolled moderate-to-severe asthma significantly reduced asthma exacerbations (AMAZES clinical trial). Objectives: We sought to test whether the 6GS predicts future exacerbation and inflammatory phenotypes in a subpopulation of AMAZES and to test the effect of AZM therapy on 6GS expression and prognostic capacity. Methods: One hundred forty-two patients (73 placebo-treated and 69 AZM-treated patients) had sputum stored for quantitative PCR of 6GS markers at baseline and after 48 weeks of treatment. Logistic regression and receiver operating characteristic and area under the curve (AUC) determination were performed on baseline measures, and in an exploratory analysis the predictive value of the 6GS was compared with conventional biomarkers for exacerbation and inflammatory phenotypes. Results: The 6GS significantly predicted all future exacerbation phenotypes tested. Calculated AUCs for the 6GS were significantly greater than AUCs for peripheral blood eosinophil counts, sputum neutrophil counts, and combined sputum eosinophil and neutrophil counts. 6GS AUCs were also numerically but not significantly greater than those for fractional exhaled nitric oxide values and sputum eosinophil counts. AZM treatment altered neither 6GS expression nor the predictive capacity of the 6GS for future exacerbation phenotypes. The 6GS was a significant predictor of airway inflammatory phenotype in this population. Conclusion: We demonstrate that a sputum gene signature can predict future exacerbation phenotypes of asthma, with the greatest biomarker performance in identifying those who would experience frequent severe exacerbations. AZM therapy did not modify 6GS expression or biomarker performance, suggesting the therapeutic action of AZM is independent of 6GS-related inflammatory pathways.

BACKGROUND:Dysfunction of the bronchial epithelium plays an important role in asthma; however, its measurement is challenging. Columnar epithelial cells are often quantified, yet rarely analysed, in induced sputum studies.OBJECTIVE:We aimed to test whether sputum columnar epithelial cell proportion and count are altered in asthma, and whether they are associated with clinical and inflammatory variables. We aimed to test whether sputum-based measures could provide a relatively non-invasive means through which to monitor airway epithelial activation status.METHODS:We examined the relationship of sputum columnar epithelial cells with clinical and inflammatory variables of asthma in a large retrospective cross-sectional cohort (901 participants with asthma and 138 healthy controls). In further studies, we used flow cytometry, microarray, qPCR and ELISA to characterize sputum columnar epithelial cells and their products.RESULTS:Multivariate analysis and generation of 90th centile cut-offs (≥11% or ≥18.1 × 104 /mL) to identify columnar epithelial cell "high" asthma revealed a significant relationship between elevated sputum columnar cells and male gender, severe asthma and non-neutrophilic airway inflammation. Flow cytometry showed viable columnar epithelial cells were present in all sputum samples tested. An epithelial gene signature (SCGB3A1, LDLRAD1, FOXJ1, DNALI1, CFAP157, CFAP53) was detected in columnar epithelial cell-high sputum. CLCA1 mRNA and periostin protein, previously identified biomarkers of IL-13-mediated epithelial activation, were elevated in columnar epithelial cell-high sputum samples, but only when accompanied by eosinophilia.CONCLUSIONS & CLINICAL RELEVANCE:Sputum columnar epithelial cells are related to important clinical and inflammatory variables in asthma. Measurement of epithelial biomarkers in sputum samples could allow non-invasive assessment of altered bronchial epithelium status in asthma.

Background Low-dose azithromycin is an effective therapy for persistent asthma; however, its benefit in severe asthma is not defined. Methods Participants with severe asthma were identified from the AMAZES randomised, placebo-controlled trial of long-term (48 weeks) low-dose azithromycin. Participants who met one of the following severe asthma definitions were included: 1) Global Initiative for Asthma step 4 treatment with poor asthma control (asthma control questionnaire score ≥0.75); 2) International Severe Asthma Registry definition; 3) American Thoracic Society and European Respiratory Society severe asthma definitions. The rate of total exacerbations was calculated for each subgroup and efficacy of azithromycin compared with placebo. Asthma-related quality of life was assessed before and after treatment along with adverse effects. Results Azithromycin significantly reduced asthma exacerbations in each group. In patients meeting the American Thoracic Society and European Respiratory Society task force definition of severe asthma (n=211), the rate of exacerbations with treatment was 1.2 per person-year, which was significantly less than for placebo (2.01 per person-year), giving an incidence rate ratio (95% CI) of 0.63 (0.41, 0.96). The proportion of participants experiencing at least one asthma exacerbation was reduced by azithromycin from 64% to 49% (p=0.021). A similar beneficial treatment effect was seen in participants poorly controlled with Global Initiative for Asthma step 4 treatment and those with International Severe Asthma Registry-defined severe asthma. Azithromycin also significantly improved the quality of life in severe asthma (p<0.05). Treatment was well tolerated, with gastrointestinal symptoms being the main adverse effect. Conclusion Long-term, low-dose azithromycin reduced asthma exacerbations and improved the quality of life in patients with severe asthma, regardless of how this was defined. These data support the addition of azithromycin as a treatment option for patients with severe asthma.

OBJECTIVE:Asthma exacerbations and medication non-adherence are significant clinical problems during pregnancy. While asthma self-management education is effective, the number of education sessions required to maximise asthma management knowledge and inhaler technique and whether improvements persist postpartum, are unknown. This paper describes how asthma knowledge, skills, and inhaled corticosteroid (ICS) use have changed over time.METHODS:Data were obtained from 3 cohorts of pregnant women with asthma recruited in Newcastle, Australia between 2004 and 2017 (N = 895). Medication use, adherence, knowledge, and inhaler technique were compared between cohorts. Changes in self-management knowledge/skills and women's perception of medication risk to the fetus were assessed in 685 women with 5 assessments during pregnancy, and 95 women who had a postpartum assessment.RESULTS:At study entry, 41%, 29%, and 38% of participants used ICS in the 2004, 2007, and 2013 cohorts, respectively (p = 0.017), with 40% non-adherence in each cohort. Self-management skills of pregnant women with asthma did not improve between 2004 and 2017 and possession of a written action plan remained low. Maximum improvements were reached by 3 sessions for medications knowledge and one session for inhaler technique, and were maintained postpartum. ICS adherence was maximally improved after one session, but not maintained postpartum. Perceived risk of asthma medications on the fetus was highest for corticosteroid-containing medication; and was significantly reduced following education.CONCLUSIONS:There was a high prevalence of non-adherence and poor self-management skills in all cohorts. More awareness of the importance of optimal asthma management during pregnancy is warranted, since no improvements were observed over the past decade.

Long-term, low-dose azithromycin reduces exacerbation frequency in chronic obstructive pulmonary disease (COPD), yet the mechanism remains unclear. This study characterised genome-wide gene expression changes in patients with neutrophilic COPD following long-term, low-dose azithromycin treatment. Patients with neutrophilic COPD (>61% or >162×104 cells per mL sputum neutrophils) were randomised to receive either azithromycin or placebo for 12 weeks. Sputum and blood were obtained before and after 12 weeks of treatment. Gene expression was defined using microarrays. Networks were analysed using the Search Tool for the Retrieval of Interacting Gene database. In sputum, 403 genes were differentially expressed following azithromycin treatment (171 downregulated and 232 upregulated), and three following placebo treatment (one downregulated and two upregulated) compared to baseline (adjusted p<0.05 by paired t-test, fold-change >1.5). In blood, 138 genes were differentially expressed with azithromycin (121 downregulated and 17 upregulated), and zero with placebo compared to baseline (adjusted p<0.05 by paired t-test, fold-change >1.3). Network analysis revealed one key network in both sputum (14 genes) and blood (46 genes), involving interferon-stimulated genes, human leukocyte antigens and genes regulating T-cell responses. Long-term, low-dose azithromycin is associated with downregulation of genes regulating antigen presentation, interferon and T-cell responses, and numerous inflammatory pathways in the airways and blood of neutrophilic COPD patients.

Macrolide antibiotics have a range of immunomodulatory properties. FKBP51 is one of four immunophilins involved in glucocorticoid receptor translocation and is highly expressed in patients with asthma taking inhaled corticosteroids. We tested the hypothesis that azithromycin (AZM) would increase gene expression for FKBP51 and that this increase would be associated with a reduction in sputum eosinophils. Induced sputum collected from adults with symptomatic asthma (n=106) in a randomized double-blind placebo controlled trial of oral AZM (500mg x 3 times weekly) was dispersed using dithiothreitol. Gene expression was quantified using reverse transcription quantitative polymerase chain reaction. Data were analysed by calculating gene expression relative to housekeeping gene, β-actin. At baseline higher sputum FKB51 expression was significantly associated with a higher ICS total daily dose in the whole study population spearman r=-0.26, p=0.002 and lower sputum eosinophils (spearman r=0.206 p=0.022). Sputum FKB51 gene expression was increased following AZM therapy (p=0.018), specifically in those participants who were prescribed <800mg (p<0.001) ICS daily but not in those prescribed ≥800mg daily (p=0.854). In those treated with AZM, the increase in FKB51 was associated with a reduction in sputum eosinophils (r=-0.299, p=0.035). Sputum FKBP51 expression was significantly increased following AZM add-on therapy in adults poorly controlled asthma prescribed low to medium doses of ICS and was associated with reduced sputum eosinophilia. Increased expression of FKBP51 may be one pathway by which AZM reduces eosinophilic airway inflammation, possibly through increasing/restoring corticosteroid responsiveness.

BACKGROUND:The single-center double-blind, randomized controlled Managing Asthma in Pregnancy (MAP) trial in Newcastle, Australia, compared a treatment algorithm using the fraction of exhaled nitric oxide (FENO) in combination with asthma symptoms (FENO group) against a treatment algorithm using clinical symptoms only (clinical group) in pregnant asthmatic women (Australian New Zealand Clinical Trials Registry, no. 12607000561482). The primary outcome was a 50% reduction in asthma exacerbations during pregnancy in the FENO group. However, the effect of FENO-guided management on the development of asthma in the offspring is unknown. OBJECTIVE:We sought to investigate the effect of FENO-guided asthma management during pregnancy on asthma incidence in childhood. METHODS:A total of 179 mothers consented to participate in the Growing into Asthma (GIA) double-blind follow-up study with the primary aim to determine the effect of FENO-guided asthma management on childhood asthma incidence. RESULTS:A total of 140 children (78%) were followed up at 4 to 6 years of age. FENO-guided as compared to symptoms-only approach significantly reduced doctor-diagnosed asthma (25.9% vs 43.2%; odds ratio [OR], 0.46, 95% CI, 0.22-0.96; P = .04). Furthermore, frequent wheeze (OR, 0.27; 95% CI, 0.09-0.87; P = .03), use of short-acting β-agonists (OR, 0.49; 95% CI, 0.25-0.97; P = .04), and emergency department visits for asthma (OR, 0.17; 95% CI, 0.04-0.76; P = .02) in the past 12 months were less common in children born to mothers from the FENO group. Doctor-diagnosed asthma was associated with common risk alleles for early onset asthma at gene locus 17q21 (P = .01 for rs8069176; P = .03 for rs8076131), and higher airways resistance (P = .02) and FENO levels (P = .03). A causal mediation analysis suggested natural indirect effects of FENO-guided asthma management on childhood asthma through "any use" and "time to first change in dose" of inhaled corticosteroids during the MAP trial (OR: 0.83; 95% CI: 0.59-0.99, and OR: 0.90; 95% CI: 0.70-1.03, respectively). CONCLUSIONS:FENO-guided asthma management during pregnancy prevented doctor-diagnosed asthma in the offspring at preschool age, in part mediated through changes in use and dosing of inhaled corticosteroids during the MAP trial.

BACKGROUND: Physical inactivity and sedentary time are distinct behaviors that may be more prevalent in severe asthma, contributing to poor disease outcomes. Physical activity and sedentary time in severe asthma however have not been extensively examined. OBJECTIVE: We aimed to objectively measure physical activity and sedentary time in people with severe asthma compared with age-matched control participants, describing the associations of these behaviors with clinical and biological outcomes. We hypothesized that people with severe asthma would be less active and more sedentary. In addition, more activity and less sedentary time would be associated with better clinical outcomes and markers of systemic and airway inflammation in people with severe asthma. METHODS: Adults with severe asthma (n [61) and sex-and age-matched controls (n [61) underwent measurement of lung function, exercise capacity, asthma control, health status, and airway and systemic inflammation. Physical activity and sedentary time were measured using an accelerometer. RESULTS: The severe asthma and control groups were matched in terms of age and sex (32 [53%] females in each group). Individuals with severe asthma accumulated less minutes per day in moderate and higher intensity activity, median (IQR) 21.9 (12.9-36.0) versus 41.7 (29.5-65.2) (P <.0001) and accumulated 2,232 fewer steps per day (P <.0002). However, they engaged in more light-intensity physical activity. No differences were found for sedentary time. In a multivariate regression model, steps per day were strongly and independently associated with better exercise capacity in participants with severe asthma (coefficient, 0.0169; 95% CI, 0.008-0.025; P <.001). CONCLUSIONS: People with severe asthma perform less moderate and vigorous activity than do controls. Higher levels of activity and lower levels of sedentary time are associated with better exercise capacity, asthma control, and lower levels of systemic inflammation. (C) 2017 American Academy of Allergy, Asthma & Immunology

Introduction: The Managing Asthma in Pregnancy (MAP) Study found an eNO-algorithm reduces exacerbations by 50% compared to a symptoms-algorithm. Aim: To determine differences between algorithm treatment decisions in MAP. Methods: Women with asthma (<23 weeks) were randomised to treatment change by a symptoms-based algorithm (control), or an eNO + symptoms-based algorithm (eNO). Treatment was adjusted monthly, using budesonide +/- formoterol. The control algorithm increased treatment for uncontrolled symptoms (ACQ>1.5) and decreased for controlled (<0.75). The eNO algorithm adjusted inhaled corticosteroid (ICS) dose by eNO (increase when >29, decrease when <16ppb), adding long acting beta agonist (LABA) for uncontrolled symptoms. Results: In 220 non-smokers (109 control, 111 eNO), 1006 treatment decisions were made. Significant group differences in treatment decision after the first and second algorithm applications were found. At first change, the eNO group was less likely to have a “no change” decision (52% vs 74%) or decrease LABA (0% vs 6%) and more likely to decrease (9% vs 1%) or increase ICS (19% vs 9%). At second change, groups differed significantly for "no change" (53% eNO bs 71% control), and increase ICS/LABA (13% eNO vs 1% control). The proportion of women on ICS differed between groups after the first change (63% vs 48%, P=0.03); ICS/LABA differed after the second change (39% vs 16%, P=0.0002). Conclusion: Group differences in algorithm treatment decisions were greatest earlier in pregnancy. The eNO algorithm permitted targeted ICS use (with more ICS titration). The increase in women using ICS+/-LABA may have contributed to reduced exacerbations.

Macrolide antibiotics have a range of immunomodulatory properties, which may influence clinical outcomes such as reduced exacerbations in patients with airways disease. Azithromycin (AZM) has been shown to reduce IL-1β release from blood monocytes, however little is known about the impact of AZM therapy on airway IL-1β. We tested the hypothesis that AZM would reduce sputum IL-1β and that this reduction would be associated with a reduction in sputum neutrophils. Induced Sputum collected from a randomized double-blind placebo controlled trial of oral AZM (500mg, 3 times weekly, 48 weeks) in adults with symptomatic asthma was dispersed using dithiothreitol and supernatant collected and assessed for IL-1β using ELISA in 195 paired samples. There was a significant reduction in sputum IL-1β following AZM therapy (median 398ng/mL at baseline to 168ng/mL following treatment, p=0.003). A significant reduction was observed in both eosinophilic (EA) and non-eosinophilic (NEA) participants, however, those with NEA had a three-fold larger reduction in IL-1β following AZM compared with EA, median change 234 ng/mL vs. 72 ng/mL, p=0.028. Baseline IL-1β was significantly positively associated with baseline neutrophil number in all participants (r = 0.499, p<0.001) and with baseline asthma control score in NEA only (r = 0.272 p=0.004) and negatively associated with FEV<1% predicted (r = -0.306 p=0.001) in NEA only. In those treated with AZM, the change in IL-1β was significantly positively associated with the change in neutrophil number (r=0.361, p<0.001). Sputum IL-1β was significantly reduced following AZM add-on therapy in poorly controlled asthma irrespective of baseline asthma phenotype.

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/m(2)), overweight (25-29.9 kg/m(2)), or obese (>30 kg/m(2)). 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. (C) 2017 American Academy of Allergy, Asthma & Immunology

Peter G. Gibson, Ian A. Yang, John W. Upham, Paul N. Reynolds, Sandra Hodge, Alan L. James, Christine Jenkins, Matthew J. Peters, Guy B. Marks, Melissa Baraket, Heather Powell, Jodie L. Simpson

BACKGROUND: Asthma and COPD are common airway diseases. Individuals with overlapping asthma and COPD experience increased health impairment and severe disease exacerbations. Efficacious treatment options are required for this population. Omalizumab (anti-IgE) therapy is effective in patients with severe persistent asthma, but limited data are available on efficacy in populations with overlapping asthma and COPD.METHODS: Data from the Australian Xolair Registry were used to compare treatment responses in individuals with asthma-COPD overlap with responses in patients with severe asthma alone. Participants were assessed at baseline and after 6 months of omalizumab treatment. We used several different definitions of asthma-COPD overlap. First, we compared participants with a previous physician diagnosis of COPD to participants with no COPD diagnosis. We then made comparisons based on baseline lung function, comparing participants with an FEV1 < 80% predicted to those with an FEV1 > 80% predicted after bronchodilator use. In the population with an FEV1 < 80%, analysis was further stratified based on smoking history.RESULTS: Omalizumab treatment markedly improved asthma control and health-related quality of life in all populations assessed based on the Asthma Control Questionnaire and Asthma Quality of Life Questionnaire scores. Omalizumab treatment did not improve lung function (FEV1, FVC, or FEV1/FVC ratio) in populations that were enriched for asthma-COPD overlap (diagnosis of COPD or FEV1 < 80%/ever smokers).CONCLUSIONS: Our study suggests that omalizumab improves asthma control and health-related quality of life in individuals with severe allergic asthma and overlapping COPD. These findings provide real-world efficacy data for this patient population and suggest that omalizumab is useful in the management of severe asthma with COPD overlap.

Background Exacerbations of asthma cause a substantial global illness burden. Adults with uncontrolled persistent asthma despite maintenance treatment require additional therapy. Since macrolide antibiotics can be used to treat persistent asthma, we aimed to assess the efficacy and safety of oral azithromycin as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high dose inhaled corticosteroids plus a long-acting bronchodilator.Methods We did a randomised, double-blind, placebo controlled parallel group trial to determine whether oral azithromycin decreases the frequency of asthma exacerbations in adults (>= 18 years) with symptomatic asthma despite current use of inhaled corticosteroid and long-acting bronchodilator, and who had no hearing impairment or abnormal prolongation of the corrected QT interval. Patients were randomly assigned (1: 1) to receive azithromycin 500 mg or placebo three times per week for 48 weeks. Patients were centrally allocated using concealed random allocation from a computer-generated random numbers table with permuted blocks of 4 or 6 and stratification for centre and past smoking. Primary efficacy endpoints were the rate of total (severe and moderate) asthma exacerbations over 48 weeks and asthma quality of life. Data were analysed on an intention-to-treat basis.Findings Between June 12, 2009, and Jan 31, 2015, 420 patients were randomly assigned (213 in the azithromycin group and 207 in the placebo group). Azithromycin reduced asthma exacerbations (1.07 per patient-year [95% CI 0.85-1.29]) compared with placebo (1.86 per patient-year [1.54-2.18]; incidence rate ratio [IRR] 0.59 [95% CI 0.47-0.74]; p<0.0001). The proportion of patients experiencing at least one asthma exacerbation was reduced by azithromycin treatment (127 [61%] patients in the placebo group vs 94 [44%] patients in the azithromycin group, p<0.0001). Azithromycin significantly improved asthma-related quality of life (adjusted mean difference, 0.36 [95% CI 0.21-0.52]; p=0.001). Diarrhoea was more common in azithromycin-treated patients (72 [34%] vs 39 [19%]; p=0.001).Interpretation Adults with persistent symptomatic asthma experience fewer asthma exacerbations and improved quality of life when treated with oral azithromycin for 48 weeks. Azithromycin might be a useful add-on therapy in persistent asthma.

Asthma exacerbations are common during pregnancy and associated with an increased risk of adverse perinatal outcomes. Adjusting asthma treatment based on airway inflammation rather than symptoms reduces the exacerbation rate by 50 %. The Breathing for Life Trial (BLT) will test whether this approach also improves perinatal outcomes.

Background: An overlap between obesity and asthma exists, and inflammatory cells in adipose tissue could drive the development of asthma. Comparison of adipose tissue gene expression among Inuit living in Greenland to those in Denmark provides an opportunity to assess how changes in adipose tissue inflammation can be modified by migration and diet.Objective: To examine mast cell and inflammatory markers in adipose tissue and the association with asthma.Methods: Two Inuit populations were recruited, one living in Greenland and another in Denmark. All underwent adipose subcutaneous biopsy, followed by clinical assessment of asthma, and measurement of AHR. Adipose tissue biopsies were homogenised, RNA extracted, and PCR was performed to determine the relative gene expression of mast cell (tryptase, chymase, CPA3) and inflammatory markers (IL-6, IL-1 beta, and CD163).Results: Of the 1059 Greenlandic Inuit participants, 556 were living in Greenland and 6.4% had asthma. Asthma was increased in Denmark (9%) compared to Greenland (3.6%, p < 0.0001) and associated with increased adipose tissue IL-6 gene expression and increased BMI. There was no association between asthma and adipose tissue mast cell gene expression. Pro-inflammatory gene expression (IL-6, IL-1 beta) was higher in those living in Denmark, and with increasing BMI and dietary changes. The anti-inflammatory (M2) macrophage marker, CD163, was higher in Greenland-dwelling Inuit (p < 0.01).Conclusions: No association was found between gene expression of mast cell markers in adipose tissue and asthma. Among Greenlandic Inuit, adipose tissue inflammation is also increased in those who migrate to Denmark, possibly as a result of dietary changes. (C) 2015 Elsevier Ltd. All rights reserved.

Objective: To describe the pattern and severity of rhinitis in pregnancy and the impact rhinitis has on asthma control and quality of life (QoL) in pregnant women with asthma. Methods: Two hundred and eighteen non-smoking pregnant women with asthma were participants in a randomised controlled trial of exhaled nitric oxide guided treatment adjustment. Rhinitis was assessed using a visual analogue scale (VAS) scored from 0 to 10 and classified as current (VAS>2.5), moderate/severe versus mild (VAS>6 vs <5), atopic versus non-atopic and pregnancy rhinitis. At baseline, women completed the 20-Item Sino-Nasal Outcome Test (SNOT20), asthma-specific (AQLQ-M) QoL questionnaires and the Six-Item Short-Form State Trait Anxiety Inventory (STAI-6). Asthma control was assessed using the asthma control questionnaire (ACQ). Perinatal outcomes were collected after delivery. Results: Current rhinitis was present in 142 (65%) women including 45 (20%) women who developed pregnancy rhinitis. Women with current rhinitis had higher scores for ACQ (p=0.004), SNOT20 (p<0.0001) and AQLQ-M (p<0.0001) compared to women with no rhinitis. Current rhinitis was associated with increased anxiety symptoms (p=0.002), rhinitis severity was associated with higher ACQ score (p=0.004) and atopic rhinitis was associated with poorer lung function (p=0.037). Rhinitis symptom severity improved significantly during gestation (p<0.0001). There was no impact on perinatal outcomes. Improved asthma control was associated with improvement in rhinitis. Conclusion: Rhinitis in pregnant women with asthma is common and associated with poorer asthma control, sino-nasal and asthma-specific QoL impairment and anxiety. In the context of active asthma management there was significant improvement in rhinitis symptoms and severity as pregnancy progressed.