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Background: Nintedanib slows lung function decline for patients with non-idiopathic pulmonary fibrosis progressive pulmonary fibrosis (PPF) in clinical trials, but the real-world safety and efficacy are not known., Methods: In this retrospective cohort study, standardised data were collected from patients in whom nintedanib was initiated for PPF between 2019 and 2020 through an early-access programme across eight centres in the United Kingdom. Rate of lung function change in the 12   months pre- and post-nintedanib initiation was the primary analysis. Symptoms, drug safety, tolerability and stratification by interstitial lung disease subtype and computed tomography pattern were secondary analyses., Results: 126 patients were included; 67 (53%) females; mean±sd age 60±13   years. At initiation of nintedanib, mean forced vital capacity (FVC) was 1.87   L (58% predicted) and diffusing capacity of the lung for carbon monoxide ( D LCO ) was 32.7% predicted. 68% of patients were prescribed prednisolone (median dose 10   mg) and 69% were prescribed a steroid-sparing agent. In the 12   months after nintedanib initiation, lung function decline was significantly lower than in the preceding 12   months: FVC -88.8 mL versus -239.9 mL (p=0.004), and absolute decline in D LCO -2.1% versus -6.1% (p=0.004). Response to nintedanib was consistent in sensitivity and secondary analyses. 89 (71%) out of 126 patients reported side-effects, but 86 (80%) of the surviving 108 patients were still taking nintedanib at 12   months with patients reporting a reduced perception of symptom decline. There were no serious adverse events., Conclusion: In PPF, the real-world efficacy of nintedanib replicated that of clinical trials, significantly attenuating lung function decline. Despite the severity of disease, nintedanib was safe and well tolerated in this real-world multicentre study., Competing Interests: Conflict of interest: I. Stewart receives funding from the Rayne Foundation. F. Chua reports personal fees from Boehringer Ingelheim. N. Chaudhuri reports personal fees from Boehringer Ingelheim, Redex, Novartis, Liminal Biosciences, Vicor Pharma, Bridge Biotherapeutics and Roche. M. Gibbons reports personal fees for advisory boards and support for attending conferences from Boehringer Ingelheim. C. Hogben has received personal fees from Boehringer Ingelheim. V. Kouranos reports personal fees from Boehringer Ingelheim and Novartis. S. Mulholland reports personal fees from Boehringer Ingelheim. M. Naqvi reports honoraria from Boehringer Ingelheim, Astra Zeneca and Roche, and grant support paid to their institution from an NHSX digital award. E.A. Renzoni reports fees paid to their institution from Boehringer Ingelheim, Novartis and Roche, and research grants paid to their institution from Boehringer Ingelheim. M. Thillai reports personal fees from Boehringer Ingelheim, research grants paid to their institution from Boehringer Ingelheim and support for conference attendance from Boehringer Ingelheim. A.U. Wells is president elect of WASOG, and reports personal fees from Boehringer Ingelheim and Roche, and support for conference from Boehringer Ingelheim. P.M. George reports personal fees from Boehringer Ingelheim, Roche, Teva, Cipla and Brainomix, research grants paid to their institution from Boehringer Ingelheim, and support for conference attendance from Boehringer Ingelheim and Roche. No other authors report any conflicts of interest., (Copyright ©The authors 2023.)

Background: Interstitial lung abnormalities (ILA) are specific spatial patterns on computed tomography (CT) scan potentially compatible with early interstitial lung disease. A proportion will progress; management involves risk stratification and surveillance. Elevated blood monocyte levels have been shown to associate with progression of idiopathic pulmonary fibrosis. The aims of the present study were: 1) to estimate the proportion of "early fibrotic" (EF)-ILAs (reticular±ground-glass opacities, excluding traction bronchiectasis and honeycombing) on CT scans of patients attending all-indications thoracic CTs, and proportion demonstrating radiological progression; and 2) to explore association between peripheral blood leukocyte levels and ILA progression., Methods: We analysed all thoracic CT reports in individuals aged 45-75 years performed between January 2015 and December 2020 in one large teaching hospital (Oxford, UK) to identify patient CT reports consistent with EF-ILA. CT-contemporaneous blood leukocyte counts were examined to explore contribution to progression and all-cause mortality, using multivariate Cox regression., Results: 40 711 patients underwent thoracic CT imaging during this period. 1259 (3.1%) demonstrated the EF-ILA pattern (mean±sd age 65.4±7.32 years; 735 (47.8%) male). EF-ILA was significantly associated with all-cause mortality (hazard ratio 1.87, 95% CI 1.25-2.78; p=0.002). 362 cases underwent at least one follow-on CT. Radiological progression was observed in 157 (43.4%) cases: increase in reticulation n=51, new traction bronchiectasis n=84, honeycombing n=22. Monocyte count, neutrophil count, monocyte:lymphocyte ratio, neutrophil:lymphocyte ratio and "systemic inflammatory response index" were significantly associated with radiological progression., Conclusion: 3.1% of subjects requiring thoracic CT during a 6-year period demonstrated EF-ILA. Monocyte levels and blood leukocyte-derived indexes were associated with radiological progression and could indicate which patients may require closer follow-up., Competing Interests: Conflict of interest: A. Achaiah has nothing to disclose. Conflict of interest: P. Lyon has nothing to disclose. Conflict of interest: E. Fraser has nothing to disclose. Conflict of interest: P. Saunders has received consultancy fees from Trevi Therapeutics and lecture fees from Boehringer Ingelheim, but no other conflict of interest. Conflict of interest: R. Hoyles has nothing to disclose. Conflict of interest: R. Benamore has nothing to disclose. Conflict of interest: L-P. Ho has nothing to disclose., (Copyright ©The authors 2022.)