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1. Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial

Author

Wannigama, Dhammika Leshan, primary, Hurst, Cameron, additional, Phattharapornjaroen, Phatthranit, additional, Hongsing, Parichart, additional, Sirichumroonwit, Natchalaikorn, additional, Chanpiwat, Kanokpoj, additional, Rad S.M., Ali Hosseini, additional, Storer, Robin James, additional, Ounjai, Puey, additional, Kanthawee, Phitsanuruk, additional, Ngamwongsatit, Natharin, additional, Kupwiwat, Rosalyn, additional, Kupwiwat, Chaisit, additional, Brimson, James Michael, additional, Devanga Ragupathi, Naveen Kumar, additional, Charuluxananan, Somrat, additional, Leelahavanichkul, Asada, additional, Kanjanabuch, Talerngsak, additional, Higgins, Paul G., additional, Badavath, Vishnu Nayak, additional, Amarasiri, Mohan, additional, Verhasselt, Valerie, additional, Kicic, Anthony, additional, Chatsuwan, Tanittha, additional, Pirzada, Kashif, additional, Jalali, Farid, additional, Reiersen, Angela M., additional, Abe, Shuichi, additional, Ishikawa, Hitoshi, additional, Tanasatitchai, Chanikan, additional, Amphol, Supamat, additional, Nantawong, Ladda, additional, Sangchan, Prangrawee, additional, Sinkajarern, Varissara, additional, Phoonakh, Thutpharritchn, additional, Utenpattanun, Phornnapat, additional, Sithu Shein, Aye Mya, additional, Vitoonpong, Timporn, additional, Chongthavonsatit, Nichapha, additional, Mankong, Yahya, additional, Chaichana, Piyapong, additional, Yaithet, Jenjira, additional, Pongprajak, Dumrongsak, additional, Traimuangpak, Sukjai, additional, Saksirisampant, Gasit, additional, Lamloeskittinon, Phimonsiri, additional, Hamdy, Adam Adam, additional, Kosasih, Sinthu Sinthu, additional, and Luk-in, Sirirat Sirirat, additional

Published
2024
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2. Exploring indoor and outdoor dust as a potential tool for detection and monitoring of COVID-19 transmission

Author

Anupong, Suparinthon, primary, Chadsuthi, Sudarat, additional, Hongsing, Parichart, additional, Hurst, Cameron, additional, Phattharapornjaroen, Phatthranit, additional, Rad S.M., Ali Hosseini, additional, Fernandez, Stefan, additional, Huang, Angkana T., additional, Vatanaprasan, Porames, additional, Saethang, Thammakorn, additional, Luk-in, Sirirat, additional, Storer, Robin James, additional, Ounjai, Puey, additional, Devanga Ragupathi, Naveen Kumar, additional, Kanthawee, Phitsanuruk, additional, Ngamwongsatit, Natharin, additional, Badavath, Vishnu Nayak, additional, Thuptimdang, Wanwara, additional, Leelahavanichkul, Asada, additional, Kanjanabuch, Talerngsak, additional, Miyanaga, Kazuhiko, additional, Cui, Longzhu, additional, Nanbo, Asuka, additional, Shibuya, Kenji, additional, Kupwiwat, Rosalyn, additional, Sano, Daisuke, additional, Furukawa, Takashi, additional, Sei, Kazunari, additional, Higgins, Paul G., additional, Kicic, Anthony, additional, Singer, Andrew C., additional, Chatsuwan, Tanittha, additional, Trowsdale, Sam, additional, Abe, Shuichi, additional, Ishikawa, Hitoshi, additional, Amarasiri, Mohan, additional, Modchang, Charin, additional, and Wannigama, Dhammika Leshan, additional

Published
2024
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3. Increased faecal shedding in SARS-CoV-2 variants BA.2.86 and JN.1

Author

Wannigama, Dhammika Leshan, primary, Amarasiri, Mohan, additional, Phattharapornjaroen, Phatthranit, additional, Hurst, Cameron, additional, Modchang, Charin, additional, Chadsuthi, Sudarat, additional, Anupong, Suparinthon, additional, Miyanaga, Kazuhiko, additional, Cui, Longzhu, additional, Fernandez, Stefan, additional, Huang, Angkana T, additional, Ounjai, Puey, additional, Singer, Andrew C, additional, Ragupathi, Naveen Kumar Devanga, additional, Sano, Daisuke, additional, Furukawa, Takashi, additional, Sei, Kazunari, additional, Leelahavanichkul, Asada, additional, Kanjanabuch, Talerngsak, additional, Chatsuwan, Tanittha, additional, Higgins, Paul G, additional, Nanbo, Asuka, additional, Kicic, Anthony, additional, Siow, Richard, additional, Trowsdale, Sam, additional, Hongsing, Parichart, additional, Khatib, Aisha, additional, Shibuya, Kenji, additional, Abe, Shuichi, additional, Ishikawa, Hitoshi, additional, Thuptiang, Wanwara, additional, Rad S.M., Ali Hosseini, additional, Vatanaprasan, Porames, additional, Jay, Dylan John, additional, Saethang, Thammakorn, additional, Luk-in, Sirirat, additional, Storer, Robin James, additional, Kanthawee, Phitsanuruk, additional, and Tacharoenmuang, Ratana, additional

Published
2024
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5. Tracing the new SARS-CoV-2 variant BA.2.86 in the community through wastewater surveillance in Bangkok, Thailand

Author

Wannigama, Dhammika Leshan, primary, Amarasiri, Mohan, additional, Phattharapornjaroen, Phatthranit, additional, Hurst, Cameron, additional, Modchang, Charin, additional, Chadsuthi, Sudarat, additional, Anupong, Suparinthon, additional, Miyanaga, Kazuhiko, additional, Cui, Longzhu, additional, Fernandez, Stefan, additional, Huang, Angkana T, additional, Ounjai, Puey, additional, Tacharoenmuang, Ratana, additional, Ragupathi, Naveen Kumar Devanga, additional, Sano, Daisuke, additional, Furukawa, Takashi, additional, Sei, Kazunari, additional, Leelahavanichkul, Asada, additional, Kanjanabuch, Talerngsak, additional, Higgins, Paul G, additional, Nanbo, Asuka, additional, Kicic, Anthony, additional, Singer, Andrew C, additional, Chatsuwan, Tanittha, additional, Trowsdale, Sam, additional, Khatib, Aisha, additional, Shibuya, Kenji, additional, Abe, Shuichi, additional, Ishikawa, Hitoshi, additional, Hongsing, Parichart, additional, Thuptiang, Wanwara, additional, Rad S M, Ali Hosseini, additional, Vatanaprasan, Porames, additional, Jay, Dylan John, additional, Saethang, Thammakorn, additional, Luk-in, Sirirat, additional, Storer, Robin James, additional, and Kanthawee, Phitsanuruk, additional

Published
2023
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6. Macrophage PD-1 associates with neutrophilia and reduced bacterial killing in early cystic fibrosis airway disease

Author

Camilla Margaroli, Hamed Horati, Luke W. Garratt, Vincent D. Giacalone, Craig Schofield, A. Susanne Dittrich, Tim Rosenow, Brian S. Dobosh, Hong S. Lim, Dario L. Frey, Mieke Veltman, George L. Silva, Milton R. Brown, Carsten Schultz, Harm A.W.M. Tiddens, Sarath Ranganathan, Joshua D. Chandler, Peng Qiu, Limin Peng, Bob J. Scholte, Marcus A. Mall, Anthony Kicic, Lokesh Guglani, Stephen M. Stick, Hettie M. Janssens, Rabindra Tirouvanziam, Pediatrics, Cell biology, and Radiology & Nuclear Medicine

Subjects
Inflammation, Pulmonary and Respiratory Medicine, Cystic Fibrosis, Bacteria, SDG 3 - Good Health and Well-being, Macrophages, Programmed Cell Death 1 Receptor, Pediatrics, Perinatology and Child Health, Humans, Child, Lung, Biomarkers
Abstract

Background: Macrophages are the major resident immune cells in human airways coordinating responses to infection and injury. In cystic fibrosis (CF), neutrophils are recruited to the airways shortly after birth, and actively exocytose damaging enzymes prior to chronic infection, suggesting a potential defect in macrophage immunomodulatory function. Signaling through the exhaustion marker programmed death protein 1 (PD-1) controls macrophage function in cancer, sepsis, and airway infection. Therefore, we sought to identify potential associations between macrophage PD-1 and markers of airway disease in children with CF. Methods: Blood and bronchoalveolar lavage fluid (BALF) were collected from 45 children with CF aged 3 to 62 months and structural lung damage was quantified by computed tomography. The phenotype of airway leukocytes was assessed by flow cytometry, while the release of enzymes and immunomodulatory mediators by molecular assays. Results: Airway macrophage PD-1 expression correlated positively with structural lung damage, neutrophilic inflammation, and infection. Interestingly, even in the absence of detectable infection, macrophage PD-1 expression was elevated and correlated with neutrophilic inflammation. In an in vitro model mimicking leukocyte recruitment into CF airways, soluble mediators derived from recruited neutrophils directly induced PD-1 expression on recruited monocytes/macrophages, suggesting a causal link between neutrophilic inflammation and macrophage PD-1 expression in CF. Finally, blockade of PD-1 in a short-term culture of CF BALF leukocytes resulted in improved pathogen clearance. Conclusion: Taken together, these findings suggest that in early CF lung disease, PD-1 upregulation associates with airway macrophage exhaustion, neutrophil takeover, infection, and structural damage.

Published
2022
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7. Ca-EDTA restores the activity of ceftazidime-avibactam or aztreonam against carbapenemase-producing Klebsiella pneumoniae infections

Author

Wannigama, Dhammika Leshan, primary, Sithu Shein, Aye Mya, additional, Hurst, Cameron, additional, Monk, Peter N., additional, Hongsing, Parichart, additional, Phattharapornjaroen, Phatthranit, additional, Fox Ditcham, William Graham, additional, Ounjai, Puey, additional, Saethang, Thammakorn, additional, Chantaravisoot, Naphat, additional, Wapeesittipan, Pattama, additional, Luk-in, Sirirat, additional, Sae-Joo, Sasipen, additional, Nilgate, Sumanee, additional, Rirerm, Ubolrat, additional, Tanasatitchai, Chanikan, additional, Kueakulpattana, Naris, additional, Laowansiri, Matchima, additional, Liao, Tingting, additional, Kupwiwat, Rosalyn, additional, Rojanathanes, Rojrit, additional, Ngamwongsatit, Natharin, additional, Tungsanga, Somkanya, additional, Leelahavanichkul, Asada, additional, Devanga Ragupathi, Naveen Kumar, additional, Badavath, Vishnu Nayak, additional, Hosseini Rad, S.M. Ali, additional, Kanjanabuch, Talerngsak, additional, Hirankarn, Nattiya, additional, Storer, Robin James, additional, Cui, Longzhu, additional, Amarasiri, Mohan, additional, Ishikawa, Hitoshi, additional, Higgins, Paul G., additional, Stick, Stephen M., additional, Kicic, Anthony, additional, Chatsuwan, Tanittha, additional, and Abe, Shuichi, additional

Published
2023
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8. Multiple traces of monkeypox detected in non-sewered wastewater with sparse sampling from a densely populated metropolitan area in Asia

Author

Wannigama, Dhammika Leshan, primary, Amarasiri, Mohan, additional, Hongsing, Parichart, additional, Hurst, Cameron, additional, Modchang, Charin, additional, Chadsuthi, Sudarat, additional, Anupong, Suparinthon, additional, Phattharapornjaroen, Phatthranit, additional, S.M., Ali Hosseini Rad, additional, Fernandez, Stefan, additional, Huang, Angkana T., additional, Kueakulpattana, Naris, additional, Tanasatitchai, Chanikan, additional, Vatanaprasan, Porames, additional, Saethang, Thammakorn, additional, Luk-in, Sirirat, additional, Storer, Robin James, additional, Ounjai, Puey, additional, Ragupathi, Naveen Kumar Devanga, additional, Kanthawee, Phitsanuruk, additional, Sano, Daisuke, additional, Furukawa, Takashi, additional, Sei, Kazunari, additional, Leelahavanichkul, Asada, additional, Kanjanabuch, Talerngsak, additional, Hirankarn, Nattiya, additional, Higgins, Paul G., additional, Kicic, Anthony, additional, Chatsuwan, Tanittha, additional, McLellan, Alexander D., additional, and Abe, Shuichi, additional

Published
2023
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10. Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis

Author

Samantha A McLean, Anthony Kicic, Barry S Clements, Sarath Ranganathan, Oded Breuer, Luke W. Garratt, Daniel R. Laucirica, Rabindra Tirouvanziam, C. Schofield, and Stephen M. Stick

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, macromolecular substances, medicine.disease_cause, Cystic fibrosis, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Bronchiectasis, medicine.diagnostic_test, biology, Pseudomonas aeruginosa, business.industry, Odds ratio, medicine.disease, Confidence interval, 030104 developmental biology, Bronchoalveolar lavage, 030228 respiratory system, Neutrophil elastase, Pediatrics, Perinatology and Child Health, Cohort, biology.protein, business
Abstract

Background: Neutrophil elastase is a significant risk factor for structural lung disease in cystic fibrosis, and Pseudomonas aeruginosa airway infection is linked with neutrophilic inflammation and substantial respiratory morbidity. We aimed to evaluate how neutrophil elastase (NE) activity changes after P. aeruginosa eradication and influences early disease outcomes. Methods: We assessed participants in the AREST CF cohort between 2000 and 2018 who had P. aeruginosa cultured from their routine annual bronchoalveolar lavage (BAL) fluid and who underwent eradication treatment and a post eradication BAL. Factors associated with persistent P. aeruginosa infection, persistent neutrophilic inflammation following eradication and worse structural lung disease one year post-eradication were evaluated. Results: Eighty-eight episodes (3 months to 6 years old) of P. aeruginosa infection were studied. Eradication was successful in 84.1% of episodes. Median activity of NE was significantly reduced post-eradication from 9.15 to 3.4 nM (p = 0.008) but persisted in 33 subjects. High post-eradication NE levels were associated with an increased risk for P. aeruginosa infection in the next annual visit (odds ratio=1.7, 95% confidence interval 1.1–2.7, p = 0.014). Post-eradication NE levels (difference, 0.8; 95% confidence interval, 0.1–1.5) and baseline bronchiectasis computed tomography (CT) score (difference, 0.4; 95% confidence interval, 0.1–0.8) were the best predictors of bronchiectasis progression within 1 year (backward stepwise linear regression model, R2= 0.608, P Conclusion: In children with CF, NE activity may persist following successful P. aeruginosa eradication and is significantly associated with bronchiectasis progression. Evaluating strategies to diminish neutrophilic inflammation is essential for improving long-term outcomes.

Published
2021
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14. Macrophage PD-1 associates with neutrophilia and reduced bacterial killing in early cystic fibrosis airway disease

Author

Margaroli, Camilla, primary, Horati, Hamed, additional, Garratt, Luke W., additional, Giacalone, Vincent D., additional, Schofield, Craig, additional, Dittrich, A. Susanne, additional, Rosenow, Tim, additional, Dobosh, Brian S., additional, Lim, Hong S., additional, Frey, Dario L., additional, Veltman, Mieke, additional, Silva, George L., additional, Brown, Milton R., additional, Schultz, Carsten, additional, Tiddens, Harm A.W.M., additional, Ranganathan, Sarath, additional, Chandler, Joshua D., additional, Qiu, Peng, additional, Peng, Limin, additional, Scholte, Bob J., additional, Mall, Marcus A., additional, Kicic, Anthony, additional, Guglani, Lokesh, additional, Stick, Stephen M., additional, Janssens, Hettie M., additional, and Tirouvanziam, Rabindra, additional

Published
2022
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16. Epithelial Mesenchymal Transition in Respiratory Disease

Author

Stephen M. Stick, Anthony Kicic, Michael Schuliga, Darryl A. Knight, and Christopher Grainge

Subjects
Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, COPD, biology, business.industry, Respiratory disease, Critical Care and Intensive Care Medicine, medicine.disease, Cystic fibrosis, Cystic fibrosis transmembrane conductance regulator, Extracellular matrix, Idiopathic pulmonary fibrosis, Fibrosis, medicine, biology.protein, Epithelial–mesenchymal transition, Cardiology and Cardiovascular Medicine, business
Published
2020
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18. Macrophage PD-1 associates with neutrophilia and reduced bacterial killing in early cystic fibrosis airway disease.

Author

Margaroli, C, Horati, H, Garratt, LW, Giacalone, VD, Schofield, C, Dittrich, AS, Rosenow, T, Dobosh, BS, Lim, HS, Frey, DL, Veltman, M, Silva, GL, Brown, MR, Schultz, C, Tiddens, HAWM, Ranganathan, S, Chandler, JD, Qiu, P, Peng, L, Scholte, BJ, Mall, MA, Kicic, A, Guglani, L, Stick, SM, Janssens, HM, Tirouvanziam, R, Margaroli, C, Horati, H, Garratt, LW, Giacalone, VD, Schofield, C, Dittrich, AS, Rosenow, T, Dobosh, BS, Lim, HS, Frey, DL, Veltman, M, Silva, GL, Brown, MR, Schultz, C, Tiddens, HAWM, Ranganathan, S, Chandler, JD, Qiu, P, Peng, L, Scholte, BJ, Mall, MA, Kicic, A, Guglani, L, Stick, SM, Janssens, HM, and Tirouvanziam, R

Abstract

BACKGROUND: Macrophages are the major resident immune cells in human airways coordinating responses to infection and injury. In cystic fibrosis (CF), neutrophils are recruited to the airways shortly after birth, and actively exocytose damaging enzymes prior to chronic infection, suggesting a potential defect in macrophage immunomodulatory function. Signaling through the exhaustion marker programmed death protein 1 (PD-1) controls macrophage function in cancer, sepsis, and airway infection. Therefore, we sought to identify potential associations between macrophage PD-1 and markers of airway disease in children with CF. METHODS: Blood and bronchoalveolar lavage fluid (BALF) were collected from 45 children with CF aged 3 to 62 months and structural lung damage was quantified by computed tomography. The phenotype of airway leukocytes was assessed by flow cytometry, while the release of enzymes and immunomodulatory mediators by molecular assays. RESULTS: Airway macrophage PD-1 expression correlated positively with structural lung damage, neutrophilic inflammation, and infection. Interestingly, even in the absence of detectable infection, macrophage PD-1 expression was elevated and correlated with neutrophilic inflammation. In an in vitro model mimicking leukocyte recruitment into CF airways, soluble mediators derived from recruited neutrophils directly induced PD-1 expression on recruited monocytes/macrophages, suggesting a causal link between neutrophilic inflammation and macrophage PD-1 expression in CF. Finally, blockade of PD-1 in a short-term culture of CF BALF leukocytes resulted in improved pathogen clearance. CONCLUSION: Taken together, these findings suggest that in early CF lung disease, PD-1 upregulation associates with airway macrophage exhaustion, neutrophil takeover, infection, and structural damage.

Published
2022

22. Preterm birth: Born too soon for the developing airway epithelium?

Author

Luke W. Garratt, Jessica Hillas, Sherlynn Ang, Shannon J. Simpson, Kevin Looi, Denby J. Evans, and Anthony Kicic

Subjects
Pulmonary and Respiratory Medicine, Neonatal intensive care unit, Resuscitation, Apoptosis, Inflammation, Respiratory Mucosa, Infections, Bioinformatics, In vitro model, Positive-Pressure Respiration, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Intensive Care Units, Neonatal, Humans, Medicine, Clinical significance, 030212 general & internal medicine, Respiratory system, Bronchopulmonary Dysplasia, Hyperplasia, business.industry, Infant, Newborn, Oxygen Inhalation Therapy, Lung Injury, medicine.disease, Chorioamnionitis, 030228 respiratory system, Bronchopulmonary dysplasia, Pediatrics, Perinatology and Child Health, Premature Birth, Respiratory epithelium, Female, Goblet Cells, medicine.symptom, business, Airway, Infant, Premature
Abstract

Birth prior to term interrupts the normal development of the respiratory system and consequently results in poor respiratory outcomes that persist throughout childhood. The mechanisms underpinning these poor respiratory outcomes are not well understood, but intrinsic abnormalities within the airway epithelium may be a contributing factor. Current evidence suggests that the airway epithelium is both structurally and functionally abnormal after preterm birth, with reports of epithelial thickening and goblet cell hyperplasia in addition to increased inflammation and apoptosis in the neonatal intensive care unit. However, studies focusing on the airway epithelium are limited and many questions remain unanswered; including whether abnormalities are a direct result of interrupted development, a consequence of exposure to inflammatory stimuli in the perinatal period or a combination of the two. In addition, the difficulty of accessing airway tissue has resulted in the majority of evidence being collected in the pre-surfactant era which may not reflect contemporary preterm birth. This review examines the consequences of preterm birth on the airway epithelium and explores the clinical relevance of currently available models whilst highlighting the need to develop a clinically relevant in vitro model to help further our understanding of the airway epithelium in preterm birth.

Published
2019
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25. Ivacaftor or lumacaftor/ivacaftor treatment does not alter the core CF airway epithelial gene response to rhinovirus

Author

De Jong, Emma, primary, Garratt, Luke W., additional, Looi, Kevin, additional, Lee, Amy H.Y., additional, Ling, Kak-Ming, additional, Smith, Maren L., additional, Falsafi, Reza, additional, Sutanto, Erika N., additional, Hillas, Jessica, additional, Iosifidis, Thomas, additional, Martinovich, Kelly M., additional, Shaw, Nicole C., additional, Montgomery, Samuel T., additional, Kicic-Starcevich, Elizabeth, additional, Lannigan, Francis J., additional, Vijayasekaran, Shyan, additional, Hancock, Robert E.W., additional, Stick, Stephen M., additional, Kicic, Anthony, additional, and AREST, CF, additional

Published
2021
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31. Development and validation of a miniaturized bacteriophage host range screening assay against antibiotic resistant Pseudomonas aeruginosa

Author

Ng, Renee Nicole, primary, Grey, Lucinda Jane, additional, Vaitekenas, Andrew, additional, McLean, Samantha Abagail, additional, Rudrum, Jack Dylan, additional, Laucirica, Daniel Rodolfo, additional, Poh, Matthew Wee-Peng, additional, Hillas, Jessica, additional, Winslow, Scott Glenn, additional, Iszatt, Joshua James, additional, Iosifidis, Thomas, additional, Tai, Anna Sze, additional, Agudelo-Romero, Patricia, additional, Chang, Barbara Jane, additional, Stick, Stephen Michael, additional, and Kicic, Anthony, additional

Published
2021
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34. Assessing the unified airway hypothesis in children via transcriptional profiling of the airway epithelium

Author

Kicic, Anthony, primary, de Jong, Emma, additional, Ling, Kak-Ming, additional, Nichol, Kristy, additional, Anderson, Denise, additional, Wark, Peter A.B., additional, Knight, Darryl A., additional, Bosco, Anthony, additional, Stick, Stephen M., additional, Kicic, Anthony, additional, Kicic-Starcevich, Elizabeth, additional, Garratt, Luke W., additional, Padros-Goosen, Marc, additional, Tan, Ee-Lyn, additional, Sutanto, Erika N., additional, Looi, Kevin, additional, Hillas, Jessica, additional, Iosifidis, Thomas, additional, Shaw, Nicole C., additional, Montgomery, Samuel T., additional, Martinovich, Kelly M., additional, Lannigan, Francis J., additional, Bergesio, Ricardo, additional, Lee, Bernard, additional, Vijaya-Sekeran, Shyan, additional, Swan, Paul, additional, Heaney, Mairead, additional, Forsyth, Ian, additional, Schoep, Tobias, additional, Larcombe, Alexander, additional, Hunter, Monica, additional, McGee, Kate, additional, Millington, Nyssa, additional, Poh, Matthew W.-P., additional, Laucirica, Daniel R., additional, Schofield, Craig, additional, McLean, Samantha, additional, Landwehr, Katherine, additional, Farrow, Nigel, additional, Roscioli, Eugene, additional, Parsons, David, additional, Grainge, Christopher, additional, Reid, Andrew T., additional, Loo, Su-Ling, additional, and Veerati, Punnam C., additional

Published
2020
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35. Toxicity of different biodiesel exhausts in primary human airway epithelial cells grown at air-liquid interface

Author

Katherine R. Landwehr, Jessica Hillas, Ryan Mead-Hunter, Andrew King, Rebecca A. O'Leary, Anthony Kicic, Benjamin J. Mullins, and Alexander N. Larcombe

Subjects
Air Pollutants, Environmental Engineering, Biofuels, Humans, Environmental Chemistry, Epithelial Cells, Particulate Matter, Pollution, Waste Management and Disposal, Gasoline, Vehicle Emissions
Abstract

Biodiesel is created through the transesterification of fats/oils and its usage is increasing worldwide as global warming concerns increase. Biodiesel fuel properties change depending on the feedstock used to create it. The aim of this study was to assess the different toxicological properties of biodiesel exhausts created from different feedstocks using a complex 3D air-liquid interface (ALI) model that mimics the human airway. Primary human airway epithelial cells were grown at ALI until full differentiation was achieved. Cells were then exposed to 1/20 diluted exhaust from an engine running on Diesel (ULSD), pure or 20% blended Canola biodiesel and pure or 20% blended Tallow biodiesel, or Air for control. Exhaust was analysed for various physio-chemical properties and 24-h after exposure, ALI cultures were assessed for permeability, protein release and mediator response. All measured exhaust components were within industry safety standards. ULSD contained the highest concentrations of various combustion gases. We found no differences in terms of particle characteristics for any of the tested exhausts, likely due to the high dilution used. Exposure to Tallow B100 and B20 induced increased permeability in the ALI culture and the greatest increase in mediator response in both the apical and basal compartments. In contrast, Canola B100 and B20 did not impact permeability and induced the smallest mediator response. All exhausts but Canola B20 induced increased protein release, indicating epithelial damage. Despite the concentrations of all exhausts used in this study meeting industry safety regulations, we found significant toxic effects. Tallow biodiesel was found to be the most toxic of the tested fuels and Canola the least, both for blended and pure biodiesel fuels. This suggests that the feedstock biodiesel is made from is crucial for the resulting health effects of exhaust exposure, even when not comprising the majority of fuel composition.

Published
2022
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36. 348: Pseudomonas aeruginosa infection modulates primary granule exocytosis

Author

Camilla Margaroli, Daniel R. Laucirica, Anthony Kicic, S. Stick, Patricia Agudelo-Romero, C. Schofield, Rabindra Tirouvanziam, Samantha A McLean, and Luke W. Garratt

Subjects
Pulmonary and Respiratory Medicine, business.industry, Pseudomonas aeruginosa, Pediatrics, Perinatology and Child Health, medicine, Primary granule, medicine.disease, business, medicine.disease_cause, Cystic fibrosis, Exocytosis, Microbiology
Published
2021
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37. 184: Regional transcriptional signatures identified in lung allograft recipients

Author

Anthony Kicic, Kak-Ming Ling, Melanie Lavender, Patricia Agudelo-Romero, M. Musk, Jeremy P. Wrobel, and S. Stick

Subjects
Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Lung, medicine.anatomical_structure, business.industry, Pediatrics, Perinatology and Child Health, medicine, medicine.disease, business, Cystic fibrosis
Published
2021
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43. Interleukin-1 is associated with inflammation and structural lung disease in young children with cystic fibrosis

Author

A. Susanne Dittrich, Lidija Turkovic, Anthony Kicic, Samuel T. Montgomery, Luke W. Garratt, Dario L. Frey, Stephen M. Stick, and Marcus A. Mall

Subjects
Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Cystic Fibrosis, Neutrophils, Inflammation, Cystic fibrosis, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Interleukin-1alpha, medicine, Humans, Correlation of Data, Lung, medicine.diagnostic_test, biology, business.industry, Interleukin, respiratory system, medicine.disease, respiratory tract diseases, 030104 developmental biology, Bronchoalveolar lavage, medicine.anatomical_structure, 030228 respiratory system, Child, Preschool, Neutrophil elastase, Pediatrics, Perinatology and Child Health, biology.protein, Respiratory epithelium, Female, medicine.symptom, Leukocyte Elastase, Tomography, X-Ray Computed, business, Bronchoalveolar Lavage Fluid
Abstract

Little is known about the role of interleukin (IL)-1 in the pathogenesis of cystic fibrosis (CF) lung disease. This study investigated the relationship between IL-1 signalling, neutrophilic inflammation and structural lung changes in children with CF.Bronchoalveolar lavage fluid (BALf) from 102 children with CF were used to determine IL-1α, IL-1β, IL-8 levels and neutrophil elastase (NE) activity, which were then correlated to structural lung changes observed on chest computed tomography (CT) scans.IL-1α and IL-1β were detectable in BAL in absence of infection, increased in the presence of bacterial infection and correlated with IL-8 (p 0.0001), neutrophils (p 0.0001) and NE activity (p 0.01 and p 0.001). IL-1α had the strongest association with structural lung disease (p 0.01) in the absence of infection (uninfected: p 0.01 vs. infected: p = 0.122).Our data associates IL-1α with early structural lung damage in CF and suggests this pathway as a novel anti-inflammatory target.

Published
2018
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49. 642: SLC6A14 is associated with lung function in patients with cystic fibrosis, regulates epithelial repair and mTOR signaling in bronchial epithelial cells

Author

Manon Ruffin, Anthony Kicic, Erika N. Sutanto, Julie Mésinèle, Claire Calmel, Julia Mercier, Pierre-Yves Boëlle, Loïc Guillot, and Harriet Corvol

Subjects
Pulmonary and Respiratory Medicine, Mtor signaling, business.industry, Pediatrics, Perinatology and Child Health, Cancer research, medicine, In patient, medicine.disease, business, Cystic fibrosis, Lung function
Published
2021
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50. The potential of phage therapy in cystic fibrosis: Essential human-bacterial-phage interactions and delivery considerations for use in Pseudomonas aeruginosa-infected airways

Author

William Ditcham, Anthony Kicic, Arest Cf, Angela Fonceca, and Stephanie Trend

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Cystic Fibrosis, Phage therapy, viruses, medicine.medical_treatment, 030106 microbiology, Biology, medicine.disease_cause, Cystic fibrosis, Microbiology, Bacteriophage, 03 medical and health sciences, Drug Delivery Systems, Immune system, Antibiotic resistance, medicine, Humans, Pseudomonas Infections, Phage Therapy, Respiratory Tract Infections, Respiratory tract infections, Pseudomonas aeruginosa, medicine.disease, biology.organism_classification, Virology, 030104 developmental biology, Pediatrics, Perinatology and Child Health, Bacteria
Abstract

As antimicrobial-resistant microbes become increasingly common and a significant global issue, novel approaches to treating these infections particularly in those at high risk are required. This is evident in people with cystic fibrosis (CF), who suffer from chronic airway infection caused by antibiotic resistant bacteria, typically Pseudomonas aeruginosa. One option is bacteriophage (phage) therapy, which utilises the natural predation of phage viruses upon their host bacteria. This review summarises the essential and unique aspects of the phage-microbe-human lung interactions in CF that must be addressed to successfully develop and deliver phage to CF airways. The current evidence regarding phage biology, phage-bacterial interactions, potential airway immune responses to phages, previous use of phages in humans and method of phage delivery to the lung are also summarised.

Published
2017
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