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  • Journal article
    Jaggi TK, Agarwal R, Tiew PY, Shah A, Lydon EC, Hage CA, Waterer GW, Langelier CR, Delhaes L, Chotirmall SHet al., 2024,

    Fungal lung disease.

    , Eur Respir J, Vol: 64

    Fungal lung disease encompasses a wide spectrum of organisms and associated clinical conditions, presenting a significant global health challenge. The type and severity of disease are determined by underlying host immunity and infecting fungal strain. The most common group of diseases are associated with the filamentous fungus Aspergillus species and include allergic bronchopulmonary aspergillosis, sensitisation, aspergilloma and chronic and invasive pulmonary aspergillosis. Fungal lung disease remains epidemiologically heterogenous and is influenced by geography, environment and host comorbidities. Diagnostic modalities continue to evolve and now include novel molecular assays and biomarkers; however, persisting challenges include achieving rapid and accurate diagnosis, particularly in resource-limited settings, and in differentiating fungal infection from other pulmonary conditions. Treatment strategies for fungal lung diseases rely mainly on antifungal agents but the emergence of drug-resistant strains poses a substantial global threat and adds complexity to existing therapeutic challenges. Emerging antifungal agents and increasing insight into the lung mycobiome may offer fresh and personalised approaches to diagnosis and treatment. Innovative methodologies are required to mitigate drug resistance and the adverse effects of treatment. This state-of-the-art review describes the current landscape of fungal lung disease, highlighting key clinical insights, current challenges and emerging approaches for its diagnosis and treatment.

  • Journal article
    Domingo-Sabugo C, Willis-Owen SAG, Mandal A, Nastase A, Dwyer S, Brambilla C, Galvez JH, Zhuang Q, Popat S, Eveleigh R, Munter M, Lim E, Nicholson AG, Lathrop GM, Cookson WOC, Moffatt MFet al., 2024,

    Genomic analysis defines distinct pancreatic and neuronal subtypes of lung carcinoid

    , JOURNAL OF PATHOLOGY, Vol: 264, Pages: 332-343, ISSN: 0022-3417
  • Journal article
    Ngo LT, Rekowski MJ, Koestler DC, Yorozuya T, Saito A, Azeem I, Harrison A, Demoruelle MK, Boomer J, England BR, Wolters P, Molyneaux PL, Castro M, Lee JS, Solomon JJ, Koronuma K, Washburn MP, Matson SMet al., 2024,

    Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease.

    , ERJ Open Res, Vol: 10, ISSN: 2312-0541

    BACKGROUND: Idiopathic interstitial pneumonias (IIPs), such as idiopathic pulmonary fibrosis and interstitial pneumonia with autoimmune features, present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF). METHODS: Patients with IIP (n=23) underwent comprehensive clinical evaluation including pre-treatment bronchoscopy and were compared with controls without lung disease (n=5). Proteomic profiling of BALF was conducted using label-free quantitative methods. Unsupervised cluster analyses identified protein expression profiles that were then analysed to predict survival outcomes and investigate associated pathways. RESULTS: Proteomic profiling successfully differentiated IIP from controls. k-means clustering based on protein expression revealed three distinct IIP clusters, which were not associated with age, smoking history, or baseline pulmonary function. These clusters had unique survival trajectories and provided more accurate survival predictions than the Gender Age Physiology index (concordance index 0.794 versus 0.709). The cluster with the worst prognosis featured decreased inflammatory signalling and complement activation, with pathway analysis highlighting altered immune response pathways related to immunoglobulin production and B-cell-mediated immunity. CONCLUSIONS: The unsupervised clustering of BALF proteomics provided a novel stratification of IIP patients, with potential implications for prognostic and therapeutic targeting. The identified molecular phenotypes underscore the diversity within the IIP classification and the potential importance of personalised treatments for these conditions. Future validation in larger, multi-ethnic cohorts is essential to confirm these findings and to explore their utility in clinical decision-making for patients with IIP.

  • Journal article
    Chotirmall SH, Chang AB, Chalmers JD, 2024,

    Infection vs Inflammation The Bronchiectasis " Tug Of War "

    , CHEST, Vol: 166, Pages: 928-930, ISSN: 0012-3692
  • Journal article
    Molyneaux P, 2024,

    The respiratory microbiome in patients with post-COVID-19 residual lung abnormalities resembles that of healthy individuals and is distinct from IPF

    , ERJ Open Research, ISSN: 2312-0541
  • Journal article
    Selvaraj M, Toghani A, Pai H, Sugihara Y, Kourelis J, Yuen ELH, Ibrahim T, Zhao H, Xie R, Maqbool A, De la Concepcion JC, Banfield MJ, Derevnina L, Petre B, Lawson DM, Bozkurt TO, Wu C-H, Kamoun S, Contreras MPet al., 2024,

    Activation of plant immunity through conversion of a helper NLR homodimer into a resistosome

    , PLoS Biology, Vol: 22, ISSN: 1544-9173

    Nucleotide-binding domain and leucine-rich repeat (NLR) proteins can engage in complex interactions to detect pathogens and execute a robust immune response via downstream helper NLRs. However, the biochemical mechanisms of helper NLR activation by upstream sensor NLRs remain poorly understood. Here, we show that the coiled-coil helper NLR NRC2 from Nicotiana benthamiana accumulates in vivo as a homodimer that converts into a higher-order oligomer upon activation by its upstream virus disease resistance protein Rx. The cryo-EM structure of NbNRC2 in its resting state revealed intermolecular interactions that mediate homodimer formation and contribute to immune receptor autoinhibition. These dimerization interfaces have diverged between paralogous NRC proteins to insulate critical network nodes and enable redundant immune pathways, possibly to minimise undesired cross-activation and evade pathogen suppression of immunity. Our results expand the molecular mechanisms of NLR activation pointing to transition from homodimers to higher-order oligomeric resistosomes.

  • Journal article
    Park Y-K, Peng H, Hapeta P, Sellés Vidal L, Ledesma-Amaro Ret al., 2024,

    Engineered cross-feeding creates inter- and intra-species synthetic yeast communities with enhanced bioproduction

    , Nature Communications, Vol: 15, ISSN: 2041-1723

    Microorganisms can be engineered to sustainably produce a variety of products including fuels, pharmaceuticals, materials, and food. However, highly engineered strains often result in low production yield, due to undesired effects such as metabolic burden and the toxicity of intermediates. Drawing inspiration from natural ecosystems, the construction of a synthetic community with division of labor can offer advantages for bioproduction. This approach involves dividing specific tasks among community members, thereby enhancing the functionality of each member. In this study, we identify six pairs out of fifteen composed of six auxotrophs of Yarrowia lipolytica that spontaneously form robust syntrophic and synergistic communities. We characterize the stability and growth dynamics of these communities. Furthermore, we validate the existence of syntrophic interactions between two yeast species, Y. lipolytica and Saccharomyces cerevisiae, and find a strain combination, Δtrp2 and Δtrp4, forming a stable syntrophic community between two species. Subsequently, we introduce a 3-hydroxypropionic acid (3-HP) biosynthesis pathway into the syntrophic community by dividing the pathway among different strains. Our results demonstrate improved production of 3-HP in both intra- and interspecies communities compared to monocultures. Our results show the stable formation of synthetic syntrophic communities, and their potential in improving bioproduction processes.

  • Journal article
    Martin AK, Mercier O, Fritz AV, Gelzinis TA, Hoetzenecker K, Lindstedt S, Marczin N, Wilkey BJ, Schecter M, Lyster H, Sanchez M, Walsh J, Morrissey O, Levvey B, Landry C, Saatee S, Kotecha S, Behr J, Kukreja J, Dellgren G, Fessler J, Bottiger B, Wille K, Dave K, Nasir BS, Gomez-De-Antonio D, Cypel M, Reed AKet al., 2024,

    ISHLT consensus statement on the perioperative use of ECLS in lung transplantation: Part II: Intraoperative considerations.

    , J Heart Lung Transplant

    The use of extracorporeal life support (ECLS) throughout the perioperative phase of lung transplantation requires nuanced planning and execution by an integrated team of multidisciplinary experts. To date, no multidisciplinary consensus document has examined the perioperative considerations of how to best manage these patients. To address this challenge, this perioperative utilization of ECLS in lung transplantation consensus statement was approved for development by the International Society for Heart and Lung Transplantation Standards and Guidelines Committee. International experts across multiple disciplines, including cardiothoracic surgery, anesthesiology, critical care, pediatric pulmonology, adult pulmonology, pharmacy, psychology, physical therapy, nursing, and perfusion, were selected based on expertise and divided into subgroups examining the preoperative, intraoperative, and postoperative periods. Following a comprehensive literature review, each subgroup developed recommendations to examine via a structured Delphi methodology. Following 2 rounds of Delphi consensus, a total of 39 recommendations regarding intraoperative considerations for ECLS in lung transplantation met consensus criteria. These recommendations focus on the planning, implementation, management, and monitoring of ECLS throughout the entire intraoperative period.

  • Journal article
    Short C, Semple T, Abkir M, Padley S, Rosenthal M, Mcnally P, Tiddens H, Caudri D, Bush A, Davies JCet al., 2024,

    Silence of the lungs: comparing measures of slow and noncommunicating lung units from pulmonary function tests with computed tomography

    , JOURNAL OF APPLIED PHYSIOLOGY, Vol: 137, Pages: 883-891, ISSN: 8750-7587
  • Journal article
    Thenappan A, Maher TM, Yazbeck L, Jenkins RG, Johnson SR, Stewart I, Oldham JM, Molyneaux PLet al., 2024,

    Competing Causes of Death in Idiopathic Pulmonary Fibrosis

    , AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 210, Pages: 938-940, ISSN: 1073-449X

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