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Background and Objective: Severe asthma (SA) is a heterogeneous disease. Transcriptomic analysis contributes to the understanding of pathogenesis necessary for developing new therapies. We sought to identify and validate mechanistic pathways of SA across two independent cohorts., Methods: Transcriptomic profiles from U-BIOPRED and Australian NOVocastrian Asthma cohorts were examined and grouped into SA, mild/moderate asthma (MMA) and healthy controls (HCs). Differentially expressed genes (DEGs), canonical pathways and gene sets were identified as central to SA mechanisms if they were significant across both cohorts in either endobronchial biopsies or induced sputum., Results: Thirty-six DEGs and four pathways were shared across cohorts linking to tissue remodelling/repair in biopsies of SA patients, including SUMOylation, NRF2 pathway and oxidative stress pathways. MMA presented a similar profile to HCs. Induced sputum demonstrated IL18R1 as a shared DEG in SA compared with healthy subjects. We identified enrichment of gene sets related to corticosteroid treatment; immune-related mechanisms; activation of CD4 + T cells, mast cells and IL18R1; and airway remodelling in SA., Conclusion: Our results identified differentially expressed pathways that highlight the role of CD4 + T cells, mast cells and pathways linked to ongoing airway remodelling, such as IL18R1, SUMOylation and NRF2 pathways, as likely active mechanisms in the pathogenesis of SA., (© 2022 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Background and Objective: Severe asthma is responsible for a disproportionate burden of illness and healthcare costs spent on asthma. This study analyses sputum transcriptomics to investigate the mechanisms and novel treatment targets of severe asthma., Methods: Induced sputum samples were collected in a cross-sectional study from participants with severe asthma (n = 12, defined as per GINA criteria), non-severe uncontrolled (n = 21) and controlled asthma (n = 21) and healthy controls (n = 15). Sputum RNA was extracted and transcriptomic profiles were generated (Illumina HumanRef-8 V2) and analysed (GeneSpring). Sputum protein lysates were analysed for p38 activation in a validation study (n = 24 asthma, n = 8 healthy) by western blotting., Results: There were 2166 genes differentially expressed between the four groups. In severe asthma, the expression of 1875, 1308 and 563 genes was altered compared to healthy controls, controlled and uncontrolled asthma, respectively. Of the 1875 genes significantly different to healthy controls, 123 were >2-fold change from which four networks were identified. Thirty genes (>2-fold change) were significantly different in severe asthma compared to both controlled asthma and healthy controls. There was enrichment of genes in the p38 signalling pathway that were associated with severe asthma. Phosphorylation of p38 was increased in a subset of severe asthma samples, correlating with neutrophilic airway inflammation., Conclusion: Severe asthma is associated with substantial differences in sputum gene expression that underlie unique cellular mechanisms. The p38 signalling pathway may be important in the pathogenesis of severe asthma, and future investigations into p38 inhibition are warranted as a 'non-Th2' therapeutic option., (© 2019 Asian Pacific Society of Respirology.)

The associations between the consumption of fast foods and asthma or allergic diseases have not been clarified. The aim of this study was to determine whether fast foods consumption is associated with asthma or allergic diseases. Databases were searched up to February 2018. Studies investigating the associations between fast foods consumption and asthma or allergic diseases were considered eligible. Included studies were assessed for quality using standardized critical appraisal checklists. The quality scores were 5.33 ± 1.16 in case-control studies and 5.69 ± 1.55 in cross-sectional studies. Adjusted odds ratios (aOR) with 95% confidence interval (CI) were pooled. Sixteen studies (13 cross-sectional and 3 case-control studies) were included. The consumption of fast foods was significantly related to current asthma (aOR: 1.58; 95% CI: 1.17-2.13 for case-control study and aOR: 1.58; 95% CI: 1.10-2.26 for cross-sectional studies), severe asthma (aOR: 1.34; 95% CI: 1.23-1.46), asthma ever (aOR: 1.36; 95% CI: 1.06-1.75), current wheeze (aOR: 1.21; 95% CI: 1.16-1.27), wheeze ever (aOR: 1.65; 95% CI: 1.07-2.52), physician-diagnosed allergic rhinitis (odds ratio: 1.43; 95% CI: 1.05-1.95), severe eczema (aOR: 1.51; 95% CI: 1.16-1.96) and severe rhino-conjunctivitis (aOR: 1.54; 95% CI: 1.18-2.00). The consumption of hamburgers was associated with current asthma (aOR: 1.59; 95% CI: 1.13-2.25), severe asthma (aOR: 1.34; 95% CI: 1.23-1.46), asthma ever (aOR: 1.47; 95% CI: 1.13-1.92), severe eczema (aOR: 1.51; 95% CI: 1.16-1.96), severe rhino-conjunctivitis (aOR: 1.54; 95% CI: 1.18-2.00) and rhino-conjunctivitis (aOR: 1.21; 95% CI: 1.15-1.27). The consumption of fast foods, especially hamburgers, ≥3 times/week, was more likely to be associated with severe asthma and current wheeze compared with the consumption of 1-2 times/week (both P < 0.001). In conclusion, the consumption of fast foods, particularly hamburgers, correlates to asthma in a dose-response pattern, which needs to be further validated in longitudinal and interventional studies., (© 2018 Asian Pacific Society of Respirology.)

Background and Objective: Obesity is an established risk factor for poor health outcomes, but paradoxically in chronic obstructive pulmonary disease (COPD), it is associated with improved survival and lung function. A major evidence gap exisits to inform treatment recommendations for patients with COPD who are obese. We aimed to determine the effect of weight reduction involving a low-energy diet utilizing a partial meal replacement plan, coupled with resistance exercise training in obese COPD patients., Methods: In a proof of concept before-after clinical trial, obese (body mass index ≥30 kg/m(2) ) COPD patients received a 12 week weight reduction programme involving meal replacements, dietary counselling by a dietitian and resistance exercise training prescribed and supervised by a physiotherapist. Patients were reviewed face to face by the dietitian and physiotherapist every 2 weeks for counselling., Results: Twenty-eight participants completed the intervention. Mean (standard deviation) body mass index was 36.3 kg/m(2) (4.6) at baseline and reduced by 2.4 kg/m(2) ((1.1) P < 0.0001) after the intervention. Importantly, skeletal muscle mass was maintained. Clinical outcomes improved with weight loss including exercise capacity, health status, dyspnea, strength and functional outcomes. There was also a significant reduction in the body mass index, obstruction, dyspnea and exercise score (BODE). Systemic inflammation measured by C-reactive protein however did not change., Conclusion: In obese COPD patients, dietary energy restriction coupled with resistance exercise training results in clinically significant improvements in body mass index, exercise tolerance and health status, whilst preserving skeletal muscle mass. This novel study provides a framework for development of guidelines for the management of obese COPD patients and in guiding future research., (© 2016 Asian Pacific Society of Respirology.)

Background and Objective: 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., Methods: Induced sputum was collected from healthy controls, asthma and COPD patients. Extracellular DNA (eDNA) was quantified by PicoGreen. LL-37, α-defensins1-3, NE, IL-1β and CXCL8 were quantified by ELISA. PAD4 and NLRP3 gene expression was performed using qPCR. NETs were imaged in sputum smears using immunofluorescence microscopy., Results: Sputum eDNA and NET neutrophil antimicrobial proteins were significantly elevated in asthma and COPD compared with healthy controls. Levels of eDNA and NET components were significantly higher in neutrophilic versus non-neutrophilic asthma and COPD. NETs were clearly visualized in sputum smears. PAD4 mRNA was upregulated in neutrophilic COPD. The level of eDNA was higher in severe asthma. High eDNA levels were associated with heightened innate immune responses, including elevated CXCL8 and IL-1β, and NLRP3 gene expression in both COPD and asthma. Antimicrobial proteins and eDNA were positively correlated with airway neutrophils, and negatively correlated with lung function and symptoms., Conclusion: NETs are present in the airways of subjects with asthma and COPD. Accumulation of excessive NETs was associated with activation of innate immune responses contributing to disease pathogenesis in chronic airway disease., (© 2016 Asian Pacific Society of Respirology.)

Background and Objective: While weight loss has been shown to reduce obesity-related comorbidity, many weight loss treatments fail. Factors that enhance weight loss success are unknown, particularly in those with asthma. The aim of the study was to identify patient characteristics that predict weight loss success in adults with asthma., Methods: Baseline and change in asthma characteristics and eating behaviours were investigated for relationships with weight loss and fat loss using multiple linear regression, in 38 overweight and obese adults with asthma randomized to dietary, exercise or combined interventions targeting weight loss for 10 weeks., Results: Mean ± standard deviation weight loss was 6.6 ± 5.1 kg. Greater %weight loss and %fat loss was achieved in those with poorer asthma-related quality of life at baseline ((rs = 0.398, P = 0.015) and (rs = 0.455, P = 0.005) respectively), with 1.7% greater absolute weight loss at week 10 corresponding to each one unit reduction in the asthma-related quality of life score at baseline. Furthermore, a lower baseline forced expiratory volume in 1 s/forced vital capacity correlated with greater weight loss (rs = 0.398, P = 0.015). Male sex was associated with a 3.6 kg greater weight loss (P = 0.087). Reducing emotional eating during the programme was associated with greater weight loss in women (rs = 0.576, P = 0.010)., Conclusions: This study demonstrates that individuals with more severe asthma at baseline are more successful in achieving weight loss, which could be a consequence of greater motivation and could be used as a motivational tool within the clinical setting. Gender tailoring of weight loss programmes may be useful to enhance weight loss success. Future studies are urgently needed to establish predictors of long-term weight loss maintenance in those with asthma., (© 2014 Asian Pacific Society of Respirology.)

Background and Objective: Dietary intake is an important modifiable risk factor for asthma and may be related to disease severity and inflammation, through the effects of intake of anti-oxidant-rich foods and pro-inflammatory nutrients. This study aimed to examine dietary intake in asthma in relation to asthma severity, lung function, inhaled corticosteroid use, leptin levels and inflammation., Methods: Food frequency questionnaires, spirometry and hypertonic saline challenge were completed by 137 stable asthmatics and 65 healthy controls. Plasma leptin was analysed by immunoassay. Induced sputum differential cell counts were determined., Results: Subjects with severe persistent asthma consumed more fat and less fibre as compared with healthy controls (odds ratio 1.04 (95% confidence interval: 1.01-1.07), P = 0.014) (odds ratio 0.94 (95% confidence interval: 0.90-0.99), P = 0.018). Among asthmatics, higher fat and lower fibre intakes were associated with lower forced expiratory volume in 1 s and airway eosinophilia. Leptin levels were increased in both male and female asthmatics as compared with healthy controls. No association existed among asthmatics between corticosteroid use and dietary intake., Conclusions: It was found that asthmatics within the subgroup of severe persistent asthma have a different pattern of dietary intake as compared with healthy controls, which was associated with lower lung function and increased airway inflammation., (© 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.)

Background and Objective: Viral nucleic acid may be detected for up to 6 months after an acute asthma deterioration, but the pattern and consequences of viral persistence after acute asthma are incompletely understood. This study investigates the frequency of viral persistence after acute asthma, assesses viral infectivity and determines the host inflammatory responses to viral persistence., Methods: Adults and children presenting to hospital with acute asthma and a confirmed respiratory virus infection were studied acutely and at recovery 4-6 weeks later by clinical evaluation and induced sputum for viral and inflammatory mediator detection., Results: Viral RNA was detected during both acute asthma and recovery visits in 17 subjects (viral persistence), whereas in 22 subjects viral RNA had cleared by recovery (viral clearance). The following viruses were detected at recovery: human rhinovirus: 16; respiratory syncytial virus: 2; influenza: 2. In subjects with viral persistence, eight isolates were different to the virus detected at Visit 1. Forty-four per cent of the human rhinovirus isolates were infective at recovery. Asthma and infection severity were similar in the viral clearance and viral persistence groups. Viral persistence was associated with elevated IL-10 mRNA and inducible protein-10 gene expression., Conclusions: Respiratory viral detection after acute asthma is common, and most often persistence is with non-infective human rhinovirus. There is a host inflammatory response with an altered cytokine environment, and the viral RNA can be source of persistent infection. These effects may have longer-term consequences in asthma., (© 2011 The Authors. Respirology © 2011 Asian Pacific Society of Respirology.)