Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis. In the last decades pirfenidone an anti-inflammatory and anti-fibrotic agent has shown benefit in inhibit collagen production and has also demonstrated benefit in decline progression in IPF in physiological outcomes as Forced vital capacity (FVC), in clinical outcomes such as progression free survival (PFS) and a benefit in mortality but no in clinically relevant outcomes as exacerbations or worsening of IPF. Methods: We conducted a systematic review to evaluate the effectiveness of physiological and clinical outcomes of pirfenidone compared to placebo in IPF. We performed a search with no language restriction. Two researchers performed literature search, quality assessment, data extraction and analysis. And was performed a summary of findings table following the GRADE approach. Results: We included 5 RCTs (Randomized controlled trials) in analysis. The meta-analysis resulted in a decrease in all cause-mortality (RR 0.52 IC 0.32–0.88) and IPF related mortality (RR 0.32 IC 0.14–0.75); other outcomes evaluated were worsening of IPF (RR 0.64 IC 0.50–0.83) and acute exacerbation (RR: 0.72 IC 0.30–1.66 respectively). Also there was a decrease in progression free survival (PFS) (RR 0.83 IC 0.74–0.92) compared to placebo. Conclusions: We observed significant differences in physiologic and clinically relevant outcomes such as reduction in all-cause mortality, IPF related mortality, worsening and exacerbation of IPF and PFS. So pirfenidone treatment should be considered not only for its benefits in pulmonary function tests but also by its clinically relevant outcomes.

BackgroundPatients often report persistent symptoms beyond the acute infectious phase of COVID-19. Hyperpolarised 129Xe MRI provides a way to directly measure airway functional abnormalities; the clinical relevance of 129Xe MRI ventilation defects in ever-hospitalised and never-hospitalised patients who had COVID-19 has not been ascertained. It remains unclear if persistent symptoms beyond the infectious phase are related to small airways disease and ventilation heterogeneity. Hence, we measured 129Xe MRI ventilation defects, pulmonary function and symptoms in ever-hospitalised and never-hospitalised patients who had COVID-19 with persistent symptoms consistent with post-acute COVID-19 syndrome (PACS).MethodsConsenting participants with a confirmed diagnosis of PACS completed 129Xe MRI, CT, spirometry, multi-breath inert-gas washout, 6-minute walk test, St. George’s Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnoea scale, modified Borg scale and International Physical Activity Questionnaire. Consenting ever-COVID volunteers completed 129Xe MRI and pulmonary function tests only.ResultsSeventy-six post-COVID and nine never-COVID participants were evaluated. Ventilation defect per cent (VDP) was abnormal and significantly greater in ever-COVID as compared with never-COVID participants (p<0.001) and significantly greater in ever-hospitalised compared with never-hospitalised participants who had COVID-19 (p=0.048), in whom diffusing capacity of the lung for carbon-monoxide (p=0.009) and 6-minute walk distance (6MWD) (p=0.005) were also significantly different. 129Xe MRI VDP was also related to the 6MWD (p=0.02) and post-exertional SpO2 (p=0.002). Participants with abnormal VDP (≥4.3%) had significantly worse 6MWD (p=0.003) and post-exertional SpO2 (p=0.03).Conclusion129Xe MRI VDP was significantly worse in ever-hospitalised as compared with never-hospitalised participants and was related to 6MWD and exertional SpO2 but not SGRQ or mMRC scores.Trial registration numberNCT05014516.

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Background In people with post-acute COVID-19 syndrome (PACS) and normal pulmonary function, 129 Xe MRI ventilation defects, abnormal quality-of-life scores, and exercise limitation were reported 3-months after infection; the longitudinal trajectory remains unclear. Purpose To measure and compare pulmonary function, exercise capacity, quality-of-life, and 129 Xe MRI ventilation defect percent (VDP) in people with PACS evaluated 3- and 15-months post-infection. Materials and Methods In this prospective study, participants with PACS aged 18-80 years were enrolled between July 2020 and August 2021 from two quaternary care centers. They were evaluated 3-months and 15-months post-infection for: 129 Xe MRI VDP, diffusing capacity of the lung for carbon monoxide (DL CO ), spirometry, oscillometry, six-minute walk distance (6MWD), and St. George's Respiratory Questionnaire (SGRQ). Differences between time-points were evaluated using paired t-tests. Multivariable models were generated to explain exercise capacity and quality-of-life improvements. Odds ratios (OR) were used to evaluate potential treatment influences. Results Fifty-three participants (mean age, 55 years ±18[SD]; 26 male; 27 female) attended both 3- and 15-month visits and were included in analysis. 129 Xe MRI VDP (5.4%, 4.2%; P =.003), forced expiratory volume in 1-second (85% pred , 90% pred ; P =.001), DL CO (89% pred , 99% pred ; P =.002) and SGRQ (35, 25; P <.001) improved between the 3- and 15-month visit. VDP measured at 3- months post-COVID predicted the change in 6MWD (β=-.643, P=.001) while treatment with respiratory medication at 3-months predicted improved 15-month quality-of-life score (OR=4.0; 95%CI:1.2,13.8, P =.03). Conclusion Pulmonary function, gas-exchange, exercise capacity, quality-of-life, and 129 Xe MRI ventilation defect percent (VDP) improved in participants with post-acute COVID-19 syndrome evaluated at 15-months as compared to 3-months post-infection. VDP measured at 3-months post-infection correlated with improved exercise capacity, whilst treatment with respiratory medication was associated with improved quality-of-life score at 15-months post-infection. Clinical Trial Registration: www.clinicaltrials.gov NCT05014516 See also the editorial by Vogel-Claussen in this issue.