Respiratory
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Research outputs from the Respiratory Medicine department at the RD&E.
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Item Investigation and outcomes in patients with nonspecific pleuritis: results from the International Collaborative Effusion database(European Respiratory Society, 2023-03-01) Sundaralingam, A.; Aujayeb, A.; Jackson, K. A.; Pellas, E. I.; Khan, II; Chohan, M. T.; Joosten, R.; Boersma, A.; Kerkhoff, J.; Bielsa, S.; Porcel, J. M.; Rozman, A.; Marc-Malovrh, M.; Welch, H.; Symonds, J.; Anevlavis, S.; Froudrakis, M.; Mei, F.; Zuccatosta, L.; Gasparini, S.; Gonnelli, F.; Dhaliwal, I.; Mitchell, M. A.; Fjaellegaard, K.; Petersen, J. K.; Ellayeh, M.; Rahman, N. M.; Burden, T.; Bodtger, U.; Koegelenberg, C. F. N.; Maskell, N. A.; Janssen, J.; Bhatnagar, R.INTRODUCTION: We present findings from the International Collaborative Effusion database, a European Respiratory Society clinical research collaboration. Nonspecific pleuritis (NSP) is a broad term that describes chronic pleural inflammation. Various aetiologies lead to NSP, which poses a diagnostic challenge for clinicians. A significant proportion of patients with this finding eventually develop a malignant diagnosis. METHODS: 12 sites across nine countries contributed anonymised data on 187 patients. 175 records were suitable for analysis. RESULTS: The commonest aetiology for NSP was recorded as idiopathic (80 out of 175, 44%). This was followed by pleural infection (15%), benign asbestos disease (12%), malignancy (6%) and cardiac failure (6%). The malignant diagnoses were predominantly mesothelioma (six out of 175, 3.4%) and lung adenocarcinoma (four out of 175, 2.3%). The median time to malignant diagnosis was 12.2 months (range 0.8-32 months). There was a signal towards greater asbestos exposure in the malignant NSP group compared to the benign group (0.63 versus 0.27, p=0.07). Neither recurrence of effusion requiring further therapeutic intervention nor initial biopsy approach were associated with a false-negative biopsy. A computed tomography finding of a mass lesion was the only imaging feature to demonstrate a significant association (0.18 versus 0.01, p=0.02), although sonographic pleural thickening also suggested an association (0.27 versus 0.09, p=0.09). DISCUSSION: This is the first multicentre study of NSP and its associated outcomes. While some of our findings are reflected by the established body of literature, other findings have highlighted important areas for future research, not previously studied in NSP.Item Clinical standards for diagnosis, treatment and prevention of post-COVID-19 lung disease(International Union Against Tuberculosis and Lung Disease, 2023-10-01) Visca, D.; Centis, R.; Pontali, E.; Zampogna, E.; Russell, A. M.; Migliori, G. B.; Andrejak, C.; Aro, M.; Bayram, H.; Berkani, K.; Bruchfeld, J.; Chakaya, J. M.; Chorostowska-Wynimko, J.; Crestani, B.; Dalcolmo, M. P.; D'Ambrosio, L.; Dinh-Xuan, A. T.; Duong-Quy, S.; Fernandes, C.; García-García, J. M.; de Melo Kawassaki, A.; Carrozzi, L.; Martinez-Garcia, M. A.; Martins, P. C.; Mirsaeidi, M.; Mohammad, Y.; Naidoo, R. N.; Neuparth, N.; Sese, L.; Silva, D. R.; Solovic, I.; Sooronbaev, T. M.; Spanevello, A.; Sverzellati, N.; Tanno, L.; Tiberi, S.; Vasankari, T.; Vasarmidi, E.; Vitacca, M.; Annesi-Maesano, I.BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice' care for the diagnosis, treatment and prevention of post-COVID-19 lung disease.METHODS: A panel of international experts representing scientific societies, associations and groups active in post-COVID-19 lung disease was identified; 45 completed a Delphi process. A 5-point Likert scale indicated level of agreement with the draft standards. The final version was approved by consensus (with 100% agreement).RESULTS: Four clinical standards were agreed for patients with a previous history of COVID-19: Standard 1, Patients with sequelae not explained by an alternative diagnosis should be evaluated for possible post-COVID-19 lung disease; Standard 2, Patients with lung function impairment, reduced exercise tolerance, reduced quality of life (QoL) or other relevant signs or ongoing symptoms ≥4 weeks after the onset of first symptoms should be evaluated for treatment and pulmonary rehabilitation (PR); Standard 3, The PR programme should be based on feasibility, effectiveness and cost-effectiveness criteria, organised according to local health services and tailored to an individual patient's needs; and Standard 4, Each patient undergoing and completing PR should be evaluated to determine its effectiveness and have access to a counselling/health education session.CONCLUSION: This is the first consensus-based set of clinical standards for the diagnosis, treatment and prevention of post-COVID-19 lung disease. Our aim is to improve patient care and QoL by guiding clinicians, programme managers and public health officers in planning and implementing a PR programme to manage post-COVID-19 lung disease.Item Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in People With Cystic Fibrosis and at Least One F508del Allele: 144-Week Interim Results From a 192-Week Open-label Extension Study(European Respiratory Society, 2023-11-09) Daines, C. L.; Tullis, E.; Costa, S.; Linnemann, R. W.; Mall, M. A.; McKone, E. F.; Polineni, D.; Quon, B. S.; Ringshausen, F. C.; Rowe, S. M.; Selvadurai, H.; Taylor-Cousar, J. L.; Withers, N. J.; Ahluwalia, N.; Moskowitz, S. M.; Prieto-Centurion, V.; Tan, Y. V.; Tian, S.; Weinstock, T.; Xuan, F.; Zhang, Y.; Ramsey, B.; Griese, M.AIMS: In two pivotal Phase 3 trials, up to 24 weeks of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in patients with cystic fibrosis ≥12 years of age who have at least one F508del allele. The aim of this study is to assess long-term safety and efficacy of ELX/TEZ/IVA in these patients. METHODS: In this Phase 3, open-label, single-arm extension study, participants with F508del-minimal function (from a 24-week parent study; n=399) or F508del-F508del (from a 4-week parent study; n=107) genotypes receive ELX/TEZ/IVA at the same dose (ELX 200 mg once daily, TEZ 100 mg once daily and IVA 150 mg every 12 h). The primary endpoint is safety and tolerability. A prespecified interim analysis was conducted when the last participant reached the Week 144 visit. RESULTS: At the Week 144 interim analysis, mean duration of exposure to ELX/TEZ/IVA in the extension study was 151.1 weeks. Exposure-adjusted rates of adverse events (586.6 events per 100 participant-years) and serious adverse events (22.4 events per 100 participant-years) were lower than in the ELX/TEZ/IVA treatment group in the 24-week parent study (1096.0 events per 100 participant-years and 36.9 events per 100 participant-years, respectively); most participants had adverse events classified as mild (16.4% of participants) or moderate (60.3% of participants) in severity. Fourteen participants (2.8%) had adverse events that led to treatment discontinuation. Following initiation of ELX/TEZ/IVA, participants had increases in per cent predicted FEV(1) (ppFEV(1)), Cystic Fibrosis Questionnaire-Revised respiratory domain score and body mass index, and had decreases in sweat chloride concentration and pulmonary exacerbations rates that were maintained over the interim analysis period. The mean annualised rate of change in ppFEV(1) was +0.07 percentage points (95% CI, -0.12 to 0.26) among the participants. CONCLUSIONS: ELX/TEZ/IVA was generally safe and well-tolerated, with a safety profile consistent with the 24-week parent study. Participants had sustained improvements in lung function, respiratory symptoms, CFTR function, pulmonary exacerbation rates and nutritional status. These results support the favourable safety profile and durable, disease-modifying clinical benefits of ELX/TEZ/IVA.Item Gastrointestinal pirfenidone adverse events in idiopathic pulmonary fibrosis depending on diet: the MADIET clinical trial(European Respiratory Society, 2023-10-19) Molina-Molina, M.; Shull, J. G.; Vicens-Zygmunt, V.; Rivera-Ortega, P.; Antoniou, K.; Bonella, F.; Renzoni, E.; Russell, A. M.; Maher, T. M.; Vancheri, A.; Bachs, A.; Avilés, V.; Palma, J.; Bermudo, G.; Suarez-Cuartin, G.; Tebé, C.; Rigo-Bonnin, R.; Montes-Worboys, A.; Wijsenbeek, M.; Vancheri, C.Individuals with IPF who follow a MUFA diet report a lower incidence of pirfenidone gastrointestinal adverse events than those that follow a SFA diet, which could explain the different prevalence in GI pirfenidone AEs reported by countries in IPF cohorts https://bit.ly/3LuzAUJ Idiopathic pulmonary fibrosis (IPF) is a chronic and lethal interstitial lung disease (ILD) [1, 2]. Antifibrotic medications such as pirfenidone have been a turning point in the management of IPF, slowing of disease progression and improving survival [1–5]. eng research projects or scientific advice from Esteve-Teijin, Roche, Boehringer Ingelheim and Chiesi. V. Vicens-Zygmunt received fees for scientific advice from Boehringer Ingelheim. P. Rivera-Ortega declares speaker and consultation fees from Boehringer Ingelheim and Hoffmann-La Roche, and fees received for research projects from Boehringer Ingelheim, Hoffmann-La Roche, CSL Behring, FibroGen, Vicore Pharma AB, Gilead Sciences and Galecto; all research fees were paid to her institution. F. Bonella declares speaker and consultation fees from Boehringer Ingelheim, Hoffman La Roche and Fibrogene, outside the submitted work. E. Renzoni reports grants, lecture fees and advisory board fees from Boehringer Ingelheim, lecture fees from Roche and Chiesi, research grants from Raynaud's and Scleroderma, and support for attending meetings from Boehringer Ingelheim, outside the submitted work; all grants and fees were paid to her institution. A-M. Russell declares speaker and consultation fees from Boehringer Ingelheim and Hoffman-La Roche. T.M. Maher reports consultancy fees from AstraZeneca, Bayer, Blade Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Galapagos, Galecto, GlaxoSmithKline, IQVIA, Pliant, Respivant Sciences, Roche/Genentech, Theravance Biopharma and Veracyte, and fees for presentations from Boehringer Ingelheim and Roche/Genentech. G. Suarez-Cuartin has received grants from Grifols, travel grants from Chiesi, Menarini and Boehringer Ingelheim, a speaker fee from Insmed, and advisory board fees from Insmed Inc. and Zambon. M. Wijsenbeek has received grants from Boehringer Ingelheim, The Netherlands Organisation for Health Research and Development, The Dutch Lung Foundation, Sarcoidose.nl and The Dutch Pulmonary Society, consulting fees from Boehringer Ingelheim, Galapagos, Bristol Myers Squibb, Galecto, Respivant, NeRRe Therapeutics, Horizon Therapeutics, PureTech health, Kinevant Sciences, Molecure and CLS Behring, speaker fees from Boehringer Ingelheim, Hoffman-La Roche, Novartis and CLS Behring, support for attending meetings from Boehringer Ingelheim, Galapagos and Hoffman-La Roche, and has participated in advisory boards of different patient associations (unpaid); all grants and fees were paid to her institution. C. Vancheri served on advisory committees of InterMune, Roche, AstraZeneca, Sanofi, Insmed, Zambon and Boehringer Ingelheim, and received lecture fees and nongovernmental research support from InterMune, Roche, Boehringer Ingelheim, Novartis, Chiesi, Menarini, AstraZeneca, GSK, Sanofi and Insmed. The rest of the authors have no relevant relationships to disclose.Item Cardiopulmonary Exercise Testing Provides Prognostic Information in Advanced Cystic Fibrosis Lung Disease(American Thoracic Society, 2023-10-25) Radtke, T.; Urquhart, D. S.; Braun, J.; Barry, P. J.; Waller, I.; Petch, N.; Mei-Zahav, M.; Kramer, M. R.; Hua-Huy, T.; Dinh-Xuan, A. T.; Innes, J. A.; McArthur, S.; Sovtic, A.; Gojsina, B.; Verges, S.; de Maat, T.; Morrison, L.; Wood, J.; Crute, S.; Williams, C. A.; Tomlinson, O. W.; Bar-Yoseph, R.; Hebestreit, A.; Quon, B. S.; Kwong, E.; Saynor, Z. L.; Causer, A. J.; Stephenson, A. L.; Schneiderman, J. E.; Shaw, M.; Dwyer, T.; Stevens, D.; Remus, N.; Douvry, B.; Foster, K.; Benden, C.; Ratjen, F.; Hebestreit, H.Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease (ACFLD) is unknown. Objectives: To determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2-years. Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1s (FEV(1)) ≤40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modelled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV(1) 30.9±5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex and FEV(1), revealed percent predicted peak oxygen uptake (V ̇O(2peak)) and peak work rate (W(peak)) as significant predictors of death/LTX: adjusted hazard ratios per each additional ten percent predicted were 0.60 (95% confidence interval, 0.43-0.90, P=0.008) and 0.60 (0.48-0.82, P<0.001). Tree-structured regression models, including a set of twelve prognostic factors for survival, identified W(peak) to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a W(peak) ≤49.2% predicted versus 10.9% for those with a W(peak) >49.2% predicted, P<0.001. Conclusions: CPET provides prognostic information in ACFLD and W(peak) appears to be a promising marker for LTX referral and candidate selection.