Background Asthma is one of the most common chronic health conditions experienced during pregnancy and is associated with numerous adverse maternal and perinatal outcomes. Aims To better understand the confidence, evidence-based knowledge and guideline use among healthcare professionals around Australia commonly involved in providing antenatal care for women with asthma. Materials and Methods An online, cross-sectional survey was developed and distributed to maternity carers (obstetricians and midwives), primary carers (general practitioners and general practice nurses) and respiratory specialists (respiratory physicians and respiratory nurses). Self-reported confidence and use of clinical guidelines were recorded. Evidence-based knowledge was assessed with 13 questions relating to four clinical scenarios that covered recommendations from national and international guidelines. Results Primary carers and respiratory specialists were more confident in providing antenatal asthma care, more likely to use clinical guidelines and scored significantly higher in evidence-based knowledge of antenatal asthma management than maternity carers (P < 0.01 and P < 0.001, respectively). There was no significant difference in evidence-based knowledge among healthcare professionals from metropolitan, regional and rural backgrounds. However, healthcare professionals who used clinical guidelines scored significantly higher than those who did not (P < 0.0001). Conclusion Greater utilisation of clinical guidelines could improve the evidence-based knowledge of maternity carers. However, the absence of antenatal asthma management in obstetric- and maternity-specific guidelines poses a potential barrier that needs to be addressed. Furthermore, the development of multidisciplinary antenatal clinics, staffed by respiratory nurses and/or physicians, could improve outcomes for pregnant women with asthma who are not undertaking shared care.

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. (C) 2019 American Academy of Allergy, Asthma & Immunology

Asthma is a common condition in preganncy and associated with perinatal complications and respiratory illness in offspring. This secondary analysis of an RCT investigated the influence of maternal body mass index (BMI) and gestational weight gain (GWG) and fractional exhaled nitric oxide (FeNO)-based management, on asthma exacerbations in pregnancy and wheeze-related outcomes in offspring. Women were randomised prior to 22 weeks gestation to asthma treatment adjustment according to symptoms (control group) or FeNO and symptoms (FeNO group). Exacerbations requiring medical intervention were recorded prospectively. Height and weight were measured at baseline, and in late pregnancy for a sub-group of women. Wheeze in infancy was determined by parent report. The incidence rate ratio (IRR) for maternal exacerbations was different between management groups for non-obese mothers (0.42, 95%CI 0.33-0.76, p=0.004, n=129) and women with GWG within recommendations (0.28, 95%CI 0.10-0.75, P=0.012, n=43), but not for obese mothers (0.59, 95%CI 0.32-1.09, P=0.09, n=88), or women with excess GWG (0.58, 95%CI 0.32-1.04, P=0.07, n=104). Recurrent bronchiolitis occurred in 5.3% of infants born to non-overweight mothers, 16.7% of infants of overweight mothers and 21.7% of infants of obese mothers in the control group. In the FeNO group, only 2 infants of obese mothers had recurrent bronchiolitis (7.1%, P=0.031). FeNO-based management reduces exacerbations in pregnancy and infant bronchiolitis, but these effects are attenuated among obese mothers and those with excess GWG, indicating the importance of weight management in contributing to improved asthma management in pregnancy.

Currently, there is a paucity of the literature describing the natural history of cholelithiasis (CL) and choledocholithiasis (CDL) in adolescent children. This study aims to analyse the changing demographics of paediatric and adolescent gallstones.

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.

BACKGROUND:Adipose tissue-derived inflammation is linked to obesity-related comorbidities. This study aimed to quantify and immuno-phenotype adipose tissue macrophages (ATMs) from obese asthmatics and obese non-asthmatics and to examine associations between adipose tissue, systemic and airway inflammation.METHODS:Visceral (VAT) adipose tissue and subcutaneous (SAT) adipose tissue were collected from obese adults undergoing bariatric surgery and processed to obtain the stromovascular fraction. Pro-inflammatory (M1) and anti-inflammatory (M2) macrophages were quantified by flow cytometry. Cytospins of induced sputum were stained for differential cell counts. Plasma C-reactive protein (CRP) and CD163 were measured by ELISA.RESULTS:VAT contained a higher number of ATMs compared to SAT. A higher percentage of M1 ATMs was observed in VAT of obese asthmatics compared to obese non-asthmatics. The M1:M2 ratio in VAT was negatively associated with FEV1 %. Sputum macrophage count was correlated positively with M1 ATMs and negatively with M2 ATMs in VAT. In obese asthmatics, CRP was positively associated with M1:M2 ratio in VAT. There were no associations with CD163. An elevated ratio of M1:M2 ATMs was observed in VAT of obese asthmatics with increased disease severity.CONCLUSIONS AND CLINICAL RELEVANCE:Visceral inflammation with increased pro-inflammatory macrophages (M1) occurs in obese asthma and may be a determinant of systemic inflammation and asthma severity.

ABSTRACT Viruses manipulate the complex interferon and interferon-stimulated gene (ISG) system in different ways. We have previously shown that HIV inhibits type I and III interferons in its key target cells but directly stimulates a subset of >20 ISGs in macrophages and dendritic cells, many of which are antiviral. Here, we examine the mechanism of induction of ISGs and show this occurs in two phases. The first phase was transient (0 to 24 h postinfection [hpi]), induced mainly by extracellular vesicles and one of its component proteins, HSP90α, contained within the HIV inoculum. The second, dominant, and persistent phase (>48 hpi) was induced via newly transcribed HIV RNA and sensed via RIGI, as shown by the reduction in ISG expression after the knockdown of the RIGI adaptor, MAVS, by small interfering RNA (siRNA) and the inhibition of both the initiation and elongation of HIV transcription by short hairpin RNA (shRNA) transcriptional silencing. We further define the induction pathway, showing sequential HIV RNA stimulation via Tat, RIGI, MAVS, IRF1, and IRF7, also identified by siRNA knockdown. IRF1 also plays a key role in the first phase. We also show that the ISGs IFIT1 to -3 inhibit HIV production, measured as extracellular infectious virus. All induced antiviral ISGs probably lead to restriction of HIV replication in macrophages, contributing to a persistent, noncytopathic infection, while the inhibition of interferon facilitates spread to adjacent cells. Both may influence the size of macrophage HIV reservoirs in vivo . Elucidating the mechanisms of ISG induction may help in devising immunotherapeutic strategies to limit the size of these reservoirs. IMPORTANCE HIV, like other viruses, manipulates the antiviral interferon and interferon-stimulated gene (ISG) system to facilitate its initial infection and establishment of viral reservoirs. HIV specifically inhibits all type I and III interferons in its target cells, including macrophages, dendritic cells, and T cells. It also induces a subset of over 20 ISGs of differing compositions in each cell target. This occurs in two temporal phases in macrophages. Extracellular vesicles contained within the inoculum induce the first, transient phase of ISGs. Newly transcribed HIV RNA induce the second, dominant ISG phase, and here, the full induction pathway is defined. Therefore, HIV nucleic acids, which are potent inducers of interferon and ISGs, are initially concealed, and antiviral ISGs are not fully induced until replication is well established. These antiviral ISGs may contribute to persistent infection in macrophages and to the establishment of viral reservoirs in vivo .

Neutrophil extracellular traps (NETs) are web‐like structures comprising DNA and antimicrobial proteins, expelled from neutrophils during NETosis. Persistence of NETs can be pro‐inflammatory, yet their role in respiratory disease remains unclear. This study aimed to investigate the presence of NETs in sputum from patients with asthma and COPD, and the relationship of NETs with inflammatory phenotype and disease severity.

Background. Innate immune antimicrobial peptides, including β-defensin-1, promote the chemotaxis and activation of several immune cells. The role of β-defensin-1 in asthma and chronic obstructive pulmonary disease (COPD) remains unclear. Methods. Induced sputum was collected from healthy controls and individuals with asthma or COPD. β-defensin-1 protein in sputum supernatant was quantified by ELISA. Biomarker potential was examined using receiver operating characteristic curves. β-defensin-1 release from primary bronchial epithelial cells (pBECs) was investigated in culture with and without cigarette smoke extract (CSE). Results. Airway β-defensin-1 protein was elevated in COPD participants compared to asthma participants and healthy controls. Inflammatory phenotype had no effect on β-defensin-1 levels in asthma or COPD. β-defensin-1 protein was significantly higher in severe asthma compared to controlled and uncontrolled asthma. β-defensin-1 protein could predict the presence of COPD from both healthy controls and asthma patients. Exposure of pBECs to CSE decreased β-defensin-1 production in healthy controls; however in pBECs from COPD participants the level of β-defensin-1 remanied unchanged. Conclusions. Elevated β-defensin-1 protein is a feature of COPD and severe asthma regardless of inflammatory phenotype. β-defensin-1 production is dysregulated in the epithelium of patients with COPD and may be an effective biomarker and potential therapeutic target.

Macrophages are key target cells for HIV-1. HIV-1(BaL) induced a subset of interferon-stimulated genes in monocyte-derived macrophages (MDMs), which differed from that in monocyte-derived dendritic cells and CD4 T cells, without inducing any interferons. Inhibition of type I interferon induction was mediated by HIV-1 inhibition of interferon-regulated factor (IRF3) nuclear translocation. In MDMs, viperin was the most up-regulated interferon-stimulated genes, and it significantly inhibited HIV-1 production. HIV-1 infection disrupted lipid rafts via viperin induction and redistributed viperin to CD81 compartments, the site of HIV-1 egress by budding in MDMs. Exogenous farnesol, which enhances membrane protein prenylation, reversed viperin-mediated inhibition of HIV-1 production. Mutagenesis analysis in transfected cell lines showed that the internal S-adenosyl methionine domains of viperin were essential for its antiviral activity. Thus viperin may contribute to persistent noncytopathic HIV-1 infection of macrophages and possibly to biologic differences with HIV-1-infected T cells.