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Background: Lung function testing remains a cornerstone in the assessment and management of interstitial lung disease (ILD) patients. The clinical implications of the Global Lung function Initiative (GLI) reference equations and the updated interpretation strategies remain uncertain., Methods: Adult patients with ILD with baseline forced vital capacity (FVC) were included from the Australasian ILD registry and the National Healthcare Group ILD registry, Singapore.The European Coal and Steel Community and Miller reference equations were compared with the GLI reference equations to assess (a) differences in lung function percent predicted values; (b) ILD risk prediction models and (c) eligibility for ILD clinical trial enrolment., Results: Among 2219 patients with ILD, 1712 (77.2%) were white individuals. Idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD and unclassifiable ILD predominated.Median FVC was 2.60 (2.01-3.36) L, forced expiratory volume in 1 s was 2.09 (1.67-2.66) L and diffusing capacity of the lungs for carbon monoxide (DLCO) was 13.60 (10.16-17.60) mL/min/mm Hg. When applying the GLI reference equations, the mean FVC percentage predicted was 8.8% lower (87.7% vs 78.9%, p<0.01) while the mean DLCO percentage predicted was 4.9% higher (58.5% vs 63.4%, p<0.01). There was a decrease in 19 IPF and 119 non-IPF patients who qualified for the nintedanib clinical trials when the GLI reference equations were applied. Risk prediction models performed similarly in predicting mortality using both reference equations., Conclusion: Applying the GLI reference equations in patients with ILD leads to higher DLCO percentage predicted values and smaller lung volume percentage predicted values. While applying the GLI reference equations did not impact on prognostication, fewer patients met the clinical trial criteria for antifibrotic agents., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process. This manuscript introduces the concept and design of an innovative research approach to drug development in fILD: a global Randomised Embedded Multifactorial Adaptive Platform in fILD (REMAP-ILD)., Methods: Description of the REMAP-ILD concept and design: the specific terminology, design characteristics (multifactorial, adaptive features, statistical approach), target population, interventions, outcomes, mission and values, and organisational structure., Results: The target population will be adult patients with fILD, and the primary outcome will be a disease progression model incorporating forced vital capacity and mortality over 12 months. Responsive adaptive randomisation, prespecified thresholds for success and futility will be used to assess the effectiveness and safety of interventions. REMAP-ILD embraces the core values of diversity, equity, and inclusion for patients and researchers, and prioritises an open-science approach to data sharing and dissemination of results., Conclusion: By using an innovative and efficient adaptive multi-interventional trial platform design, we aim to accelerate and improve care for patients with fILD. Through worldwide collaboration, novel analytical methodology and pragmatic trial delivery, REMAP-ILD aims to overcome major limitations associated with conventional randomised controlled trial approaches to rapidly improve the care of people living with fILD., Competing Interests: Competing interests: LK-D—research grants from Boehringer Ingelheim and Bristol-Myers-Squibb, research grant from the Brazilian Ministry of Health (PROADI-SUS), non-financial research support from Fisher & Paykel; personal fees from Sarava and Boehringer Ingelheim. TK—personal fees from Boehringer Ingelheim, United Therapeutics, Puretech and Veracyte. CJR—research grant from Boehringer Ingelheim; personal fees from Boehringer Ingelheim, Pliant Therapeutics, AstraZeneca, Trevi Therapeutics, Hoffmann La Roche and Cipla. PR-O—research grants from Boehringer Ingelheim, Hoffmann La Roche, CSL Behring, FibroGen, Vicore Pharma, Gilead, Galecto and Chiesi; personal fees from Boehringer Ingelheim, Hoffmann La Roche, Cipla, Tecnofarma, Respiratory Effectiveness Group and The Limbic. NC—personal fees from Boehringer Ingelheim, Liminal Biosciences, Vicor Pharma, Bridge Biotherapeutics and Transcrip. MF-C—research grants from CSL Behring, Boehringer Ingelheim and Roche; personal fees from Boehringer Ingelheim, MSD, AstraZeneca and GSK. A-MH-V—research grants from Boehringer Ingelheim and Janssen; personal fees from ARXX, Boehringer Ingelheim, Janssen, Medscape, Roche, Genentech, Bayer, Lilly and Merck Sharp & Dohme. KAJ—research grants from University Hospital Foundation and Three Lakes Foundation; personal fees from Boehringer Ingelheim, Pliant, Thyron, Brainomix and Hoffman La Roche. YHK—research grants from NHMRC, MRFF, Air Liquide Healthcare, Austin Medical Research Foundation, Lung Foundation Australia/Thoracic Society of Australia and New Zealand, and RACP. SBM—research grants from Three Lakes Foundation, NIH/NHLBI, Merck, Boehringer Ingelheim, Pliant Therapeutics, American Thoracic Society, and National Scleroderma Foundation; personal fees from Wolters Kluwer, Roche, DevPro Biopharma, Gilead, Accendatech, Cowen and APIE Therapeutics. LP—research grants from Janssen and Ferrer; personal fees from Janssen, Ferrer, United Therapeutics, MSD and Liquidia. HP—research grants from Boehringer Ingelheim, AstraZeneca and Siemens; personal fees from Boehringer Ingelheim, Sanofi, Janssen, MSD, AstraZeneca and Chiesi. MM-M—research grants from Boehringer Ingelheim and Roche; personal fees from Boehringer Ingelheim, Ferrer and Chiesi. JST—research grant from Boehringer Ingelheim; personal fees from Boehringer Ingelheim and Aflofarm. SR—personal fees from Cipla and Boehringer Ingelheim. JJ—research grants from Gilead, Microsoft research and GSK; personal fees from Boehringer Ingelheim, Roche, GSK and Takeda. DR—research grants from NIHR; personal fees from OMass Therapeutics, Sosei Heptares and GSK. LGS—personal fees from Daiichi Sankyo and Chiesi. MK—research grants from Boehringer Ingelheim and Roche; personal fees from Nichtraucherhelden/Sanero, Boehringer Ingelheim and Roche. NK—research grants from Veracyte, Boehringer Ingelheim, BMS and non-financial support from AstraZeneca; scientific founder at Thyron; personal fees from Boehringer Ingelheim, Pliant, AstraZeneca, RohBar, Veracyte, Augmanity, CSL Behring, Splisense, Galapagos, Fibrogen, GSK, Merck and Thyron; and reports Equity in Pliant and Thyron. RL—senior consultant for Berry Consultants. WA—personal fees from Boehringer Ingelheim. GJ—research grants from AstraZeneca, Biogen, Galecto, GSK, Nordic Biosciences, RedX and Pliant; personal fees from Apollo Therapeutics, AstraZeneca, Brainomix, Bristol-Myers-Squibb, Chiesi, Cohbar, Daewoong, Veracyte, GSK, Resolution Therapeutics, Pliant, Hoffmann La Roche, PatientMPower, Pinsent Masons, Galapagos and Vicore Pharma. BGB, IB-V, BW, TJ, MQ and VC have no conflicts to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with interstitial lung disease (ILD) are at risk of developing nocturnal hypoxaemia due to ventilatory restriction and impaired gas exchange that worsen with supine posture and reduced ventilatory drive during sleep. This systematic review synthesised literature on the diagnostic evaluation, epidemiology, associations, management and prognosis of nocturnal hypoxaemia in ILD., Methods: Ovid MEDLINE, Embase and CENTRAL databases were searched for eligible studies. Meta-analyses with subgroup analyses were conducted, where possible., Results: Fifty-three studies were included (total participant number=2590). The most common definition for clinically significant nocturnal hypoxaemia was ≥10% of total sleep time with oxyhaemoglobin saturation <90%, with pooled prevalence of 37%. There were no significant differences in pooled prevalence according to ILD subtype and comorbid obstructive sleep apnoea status. Study heterogeneity precluded meta-analysis of associations and prognosis. Diffusing capacity for carbon monoxide (DLCO) and echocardiographic features for pulmonary hypertension were consistently associated with nocturnal hypoxaemia. There were inconsistent associations between nocturnal hypoxaemia with ILD subtype and severity. Multivariable analyses in most studies demonstrated significant associations of nocturnal hypoxaemia with survival. Two small short-term intervention studies demonstrated that supplemental oxygen of 1-3 L/min corrected nocturnal hypoxaemia, with improved heart rate control during in-laboratory observation and increased serum antioxidant levels after 1 month of therapy., Conclusion: Nocturnal hypoxaemia is common, associated with DLCO impairment and markers suggestive of pulmonary hypertension, and a potential prognostic factor in patients in ILD. There is a need to establish a consensus definition of nocturnal hypoxaemia and evaluate long-term effects of nocturnal supplemental oxygen in ILD., Competing Interests: Competing interests: YHK reports non-financial trial support from Air Liquide Healthcare, outside the submitted work., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)