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Jungle animals
Introduces animals that live in the jungle, discussing how they move, find food, and appear.
Book
S146 Aspergillus in bronchiectasis: data from the EMBARC registry
Introduction Aspergillus fumigatus causes airway disorders including Allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitisation (AS) and Aspergillus bronchitis (AB). The clinical significance of Aspergillus lung diseases in bronchiectasis is not well understood, partially due to no universally-accepted diagnostic criteria for ABPA.ObjectiveInvestigate the clinical significance of Aspergillus disease in bronchiectasis while comparing existing and modified ABPA diagnostic criteria.MethodsBronchiectasis patients enrolled into the EMBARC registry from 2015–2022 with serological testing for Aspergillus disease (total IgE, Aspergillus-specific IgE or Aspergillus skin test, Aspergillus-specific IgG and blood eosinophil counts) were included. ABPA was defined using Modified-ISHAM criteria (2021) with sensitivity analysis performed using ISHAM-ABPA criteria (2013). Elevated Aspergillus-specific IgE/positive Aspergillus skin test without ABPA was deemed ‘AS’. Those with elevated Aspergillus-specific IgG without ABPA acted as surrogate for AB. Patients not meeting these criteria formed the control group. Exacerbations during annual follow-up were analysed using negative binomial modelling and survival analysis was performed using Cox proportional hazards regression with adjustment for relevant confounders.Results9953 patients were included. Using Modified-ISHAM criteria (2021), 608 (6.1%) had ABPA, 570 (5.7%) showed AS, 806 (8.1%) had raised Aspergillus-specific IgG, 184 (1.8%) had both AS and raised Aspergillus-specific IgG and 619 (6.2%) had elevated eosinophil counts without Aspergillus disease. 78 ABPA diagnoses were missed using the original ISHAM-ABPA criteria (2013) (31 previously AS, 47 previously AS with raised Aspergillus-specific IgG). All patients with Aspergillus disease had more severe bronchiectasis and worse lung function at baseline. Long-term follow-up revealed patients with raised Aspergillus-specific IgG experience more exacerbations (RR1.19 95%CI 1.05–1.35, p=0.008) and more frequent hospitalisations (RR1.66 95%CI 1.37–1.99, p<0.001), while a trend towards increased mortality was observed in those with ABPA (HR 1.40 95%CI 0.99–1.99, p=0.057). Inhaled corticosteroids modified hospitalisation risk associated with AS (RR0.70 95%CI 0.54–0.90, p=0.006 vs RR0.91 95%CI 0.54–1.52, p=0.71) and raised Aspergillus-specific IgG (RR1.32 95%CI 1.04–1.68, p=0.02 vs RR2.26 95%CI 1.68–3.02, p<0.001).Conclusion Aspergillus disease is common in bronchiectasis and associates with worsened disease severity and outcomes which can be modified by ICS. The Modified-ISHAM criteria (2021) captured ABPA diagnoses that would have been missed using existing ISHAM-ABPA criteria (2013).Please refer to page A288 for declarations of interest related to this abstract.
Journal Article
S144 Failure to repair: an in vitro model of aspergillus fumigatus infection in airway epithelial injury
Question: How does the ubiquitous environmental mould, Aspergillus fumigatus, impact bronchial epithelial cells (BECs) during injury? This study aimed to assess an in vitro model of host-pathogen interaction with the underlying hypothesis that A.f. infection disrupts lung epithelial repair in disease.Background A.f. causes a broad spectrum of life-threatening invasive and allergic respiratory diseases in over 18 million individuals worldwide. The impact of A.f. infection during co-morbid acute and chronic respiratory diseases has been identified but the underlying mechanistic basis of this is unclear.MethodologyTo mimic lung barrier damage, we employed a scratch assay on CM-DiI labelled 16HBE14o- cell (BEC) monolayers on 0.4μm pore transwells cultured in MEMα containing 10% FBS. Scratch closure in the presence and absence of transgenic GFP+ A. fumigatus was measured using timelapse fluorescence microscopy. Epithelial migration velocity was calculated using non-linear regression with the Levenberg-Marquardt algorithm. To determine epithelial uptake of spores, BEC were isolated at different time points of the culture and spore uptake was measured via flow cytometry.ResultsWhile we found wound closure occurred within 12–18 hours (mean maximum closure 97.2%), this was prevented in the presence of live A.f. spores (MOI 10:1, mean maximum closure 54.9%). Spore inhibition of wound closure was associated with presence of mycelium growth. Furthermore, addition of spores to BEC cultures 24h prior to scratch wounding dramatically inhibited wound closure (mean maximum closure 3.9%). Despite this, epithelial velocity during wound repair between 3–7 hours post scratch was increased in the presence of spores (MOI 1:1000, 0.28 μm/h; 1:100, 0.47 μm/h; 1:10, 0.58 μm/h). Finally, flow cytometry analysis showed that spores were not internalised by epithelial cells (uptake 0.50–0.66 %), showing that the impact of A.f. epithelial cell wound closure and cell velocity was not due to epithelial cell uptake of spores.ConclusionsBEC wound repair accelerates and then fails during A.f. infection in a dose-dependent manner. Further research should explore the reproducibility of these preliminary findings and the mechanisms underlying wound repair failure. Potential candidates include A.f. secreted factors as mediators of altered BEC cytoskeletal function and epithelial migration.Please refer to page A288 for declarations of interest related to this abstract.
Journal Article
Jungle survival guide
Find out where to find clean drinking water, what plants (and bugs!) are safe to eat, and how to avoid being bitten alive by mosquitos.
Book
S142 Low fungal diversity with candida, cladosporium and papiliotrema-dominance in eosinophilic lung diseases: a cross-sectional bronchoscopic study
IntroductionEosinophilic Lung Diseases (ELDs), including Chronic Eosinophilic Pneumonia (CEP), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Allergic Bronchopulmonary Aspergillosis (ABPA) are uncommon conditions linked to asthma. Fungi are implicated in ABPA but the aetiology of other ELDs is unknown. No studies have yet described the fungal communities in CEP or EGPA.ObjectivesTo determine the fungal biomass and characterise the fungal communities in the upper and lower airways of ELD patients.MethodsBronchoscopic evaluation of the Eosinophilic Airway Microbiome (BEAM) was a cross-sectional observational study. Subjects undertook questionnaires, blood tests and spirometry. Each provided an oropharyngeal throat-swab (OTS) and endobronchial brushings. Samples underwent DNA extraction, 18S quantitative PCR and massively-parallel next-generation ITS2 sequencing. Data were pre-processed in Quantitative Insights Into Microbial Ecology (QIIME) 2 and analysed in R. Samples were rarefied; Those with <1,000 reads were excluded from downstream analyses.ResultsTwenty-one subjects were recruited: 11 ELD patients (7 CEP, 3 EGPA, 1 ABPA) and 10 healthy controls. The mean (SD) age was 50.6 yrs (9.8) in cases and 51 (9.4) in controls. All cases (no controls) were using inhaled corticosteroids (ICS). The blood eosinophil count was 0.39x109/L (0.4) in cases and 0.08x109/L (0.1) in controls. Fungal biomass was significantly higher in OTS than brushes: OTS mean 20,675 18S copies/sample vs brushes 4,950 copies/sample (P=0.036). Fungal biomass did not correlate with blood eosinophil count or FEV1. Twelve OTS and 7 brushes had >1,000 reads. Data analysis revealed fungal diversity was low in all samples with each being dominated by a single genus. The most common genera in OTS were Candida, Aureobasidium and Cladosporium, and in brushes Candida and Papiliotrema. Brushings from all three EGPA subjects were dominated by Papiliotrema.ConclusionsDifferences were observed between the dominant organisms in healthy controls (usually Aureobasidium), and ELDs (Candida-dominance of the upper and lower airways, Cladosporium [upper airways] and/or Papiliotrema [lower airways]). Such differences may be influenced by ICS use. The results of this study suggest mechanistic studies of potential immune-modulatory actions of fungi in ELDs are warranted to determine whether fungal dysbiosis is a trigger for and/or perpetuator of disease.
Journal Article
The monkey and the ladybird
\"Min Monkey watches different animals walk by before being surprised by a little ladybird.\"--Provided by publisher.
Book
Ecological and socio-economic functions across tropical land use systems after rainforest conversion
Tropical lowland rainforests are increasingly threatened by the expansion of agriculture and the extraction of natural resources. In Jambi Province, Indonesia, the interdisciplinary EFForTS project focuses on the ecological and socio-economic dimensions of rainforest conversion to jungle rubber agroforests and monoculture plantations of rubber and oil palm. Our data confirm that rainforest transformation and land use intensification lead to substantial losses in biodiversity and related ecosystem functions, such as decreased above- and below-ground carbon stocks. Owing to rapid step-wise transformation from forests to agroforests to monoculture plantations and renewal of each plantation type every few decades, the converted land use systems are continuously dynamic, thus hampering the adaptation of animal and plant communities. On the other hand, agricultural rainforest transformation systems provide increased income and access to education, especially for migrant smallholders. Jungle rubber and rubber monocultures are associated with higher financial land productivity but lower financial labour productivity compared to oil palm, which influences crop choice: smallholders that are labour-scarce would prefer oil palm while land-scarce smallholders would prefer rubber. Collecting long-term data in an interdisciplinary context enables us to provide decision-makers and stakeholders with scientific insights to facilitate the reconciliation between economic interests and ecological sustainability in tropical agricultural landscapes.
Journal Article
S145 The fungal burden in nontuberculous mycobacterial pulmonary disease
Introduction and ObjectivesFungal lung infections may complicate the clinical trajectories of individuals with nontuberculous mycobacterial pulmonary disease (NTM-PD). It remains unclear whether NTM infection or therapies predispose to fungal disease. We hypothesised that there are differences in pulmonary fungal burden in NTM-PD according to NTM species, NTM treatment use and underlying structural lung diseases. We aimed to quantify this longitudinally in people with NTM-PD.MethodsSputum samples were acquired at baseline, weekly for 4 weeks and monthly up to 3 months from 37 participants who: had NTM-PD requiring treatment; had NTM-PD not requiring treatment; or did not have NTM-PD. Additional samples were collected monthly from those on NTM treatment until 12 months; then 3-monthly until 18 months. Sputum DNA was extracted using hexadecyl-trimethyl-ammonium bromide phenol chloroform. Total fungal burden was quantified using 18S rRNA gene quantitative polymerase chain reaction.ResultsThere was no difference in pulmonary fungal burden at baseline or 3 months between: individuals with or without NTM-PD; those with Mycobacterium avium complex pulmonary disease (MAC-PD) or Mycobacterium abscessus pulmonary disease (MAB-PD); those on or off NTM treatment; or those with bronchiectasis, cystic fibrosis or chronic obstructive pulmonary disease. Fungal burden was higher in MAB-PD than MAC-PD (P<0.05) following 6 months of NTM treatment; no difference was observed at 12 or 18 months. Among those on NTM treatment, there was no difference in the change in fungal burden that occurred between baseline and 6, 12 or 18 months according to NTM species or underlying lung disease.ConclusionNo difference in pulmonary fungal burden between individuals with or without NTM-PD was found. In NTM-PD, no difference was observed in fungal burden according to underlying lung disease, NTM species (except at 6 months if on NTM treatment) or NTM therapy. NTM treatment was not associated with changes in fungal burden at 6, 12 or 18 months relative to baseline. Fungal burden alone is therefore unlikely to explain the clinical associations between NTM-PD and fungal sequelae. Using internal transcribed spacer 2 sequencing to evaluate the relationship between fungal diversity and NTM species, therapies and outcomes is therefore warranted.Please refer to page A288 for declarations of interest related to this abstract.
Journal Article