Influenza-associated acute respiratory deterioration fulfilling acute exacerbation criteria in hospitalized patients with interstitial lung disease: a single-center retrospective cohort study

Background Acute exacerbation (AE) of interstitial lung disease (ILD) is life threatening, but data on acute respiratory deterioration fulfilling AE criteria after laboratory-confirmed influenza infection are limited. The current study investigated the incidence, clinical features, and outcomes of such events after laboratory-confirmed influenza in hospitalized patients with ILD. Methods We retrospectively reviewed adults with pre-existing ILD who were hospitalized with influenza at Toranomon Hospital between April 2014 and April 2019. Influenza was confirmed by rapid diagnostic tests. Fulfillment of the AE criteria was confirmed by two pulmonologists and one radiologist. Baseline characteristics and outcomes were compared between patients with and without AE-criteria events. The Mann–Whitney U test or Fisher’s exact test were used for between-group comparisons, and the Kaplan–Meier method and the log-rank test were used for survival analysis. Results Of 927 patients hospitalized with ILD during the study period, 47 had laboratory-confirmed influenza, and 10 of these patients (21.3%) developed AE-criteria events. The median interval from influenza diagnosis to event onset was 5.0 days. Compared with patients without AE-criteria events, those with AE-criteria events had lower percent predicted forced vital capacity (70.0% versus 88.0%, p = 0.041) and higher ILD-GAP stage. The in-hospital mortality rate in patients with AE-criteria events was 30.0%. Overall survival from influenza diagnosis appeared shorter in patients with AE-criteria events in unadjusted analysis. Conclusions Acute respiratory deterioration fulfilling AE criteria occurred in approximately one fifth of hospitalized patients with ILD after laboratory-confirmed influenza and was associated with high in-hospital mortality. Unadjusted analysis also suggested shorter overall survival in these patients. These findings should be considered exploratory and hypothesis-generating, and require confirmation in larger multicenter studies.