After reviewing 922 citations, 41 international experts extended the acute exacerbation definition from IPF to all fibrotic interstitial lung diseases and proposed a new acute respiratory worsening framework

Proposed a revised AE-fILD definition: an acute respiratory event with increased respiratory symptoms or signs and radiologic or histologic features consistent with diffuse alveolar damage (DAD, with or without superimposed organizing pneumonia) in a patient with known or newly diagnosed fILD. The 2016 definition applied only to IPF and lacked a standardized approach for non-IPF fILD; the new definition extends across all fILDs and anchors the definition in DAD to maintain diagnostic specificity and prognostic relevance. Based on a systematic search of 922 citations with narrative synthesis and random-effects meta-analyses for cumulative incidence, clinical features, mortality, and treatment effects; clinical criteria added hypoxemia (prevalence over 90% in published literature) and retained a symptom-onset window of typically less than 1 month (mean symptom duration 14 days, 95% CI 5-22 days).

Proposed the broader construct of acute respiratory worsening (ARW) to describe heterogeneous acute deteriorations in fILD patients not attributable to DAD, such as airway infection, COPD exacerbation, pleural effusion, pneumothorax, pulmonary edema, pulmonary embolism, and respiratory muscle weakness. Previously, acute deteriorations in fILD were often lumped into AE; the ARW framework explicitly separates AE from non-AE events and notes that the latter are often transient with good recovery and more favorable prognosis, reducing misclassification. Based on literature synthesis of causes of acute deterioration in fILD and alignment with the framework applied to chronic ILD; the document also distinguishes ARW from rapidly progressive ILD (e.g., anti-MDA5 dermatomyositis-associated ILD).

Summarized prognosis of AE-fILD: estimated 30-day mortality of 30% (95% CI 25%-35%) and 1-year mortality of 56% (95% CI 47%-63%); in-hospital mortality rates are as high as 80% for patients with AE-fILD requiring ICU admission. Extends prognostic evidence previously derived mainly from IPF to non-IPF fILD, and notes that AE-IPF generally has higher mortality than AE of non-IPF fILD, with pooled mortality higher using the 2007 definition compared to the 2016 definition. Based on random-effects meta-analyses; however, the document states most studies reporting mortality are retrospective and at risk of selection and misclassification bias.

Systematically reviewed treatment evidence for AE-fILD: no therapeutic interventions are definitively proven to improve outcomes, management remains primarily supportive; high-dose systemic corticosteroids remain the most widely used therapy despite lack of RCT-based data and may have differential effects between IPF and non-IPF fILD; antifibrotic evidence for preventing AE is heterogeneous. Organized treatment evidence into prevention and treatment sections and incorporated recent RCT results (e.g., intravenous cyclophosphamide conferred no survival benefit, a recent rhTM RCT showed no survival benefit with increased bleeding events, and high-dose nerandomilast was associated with reduced AE risk among patients with PPF). Most studies are of low quality with small sample size and retrospective data collection; the only RCT examining immunomodulatory medications in AE-IPF (intravenous cyclophosphamide) showed no survival benefit; the first placebo-controlled RCT of systemic corticosteroids for AE-IPF (EXAFIP2) is currently in progress.

This document is intended for clinicians, ILD specialty centers, clinical trial designers, and researchers, and applies to patients with known or newly diagnosed fILD presenting with acute respiratory worsening. Its definition and ARW framework are designed for use in both hospitalized and outpatient settings, as well as in clinical practice and research. The diagnostic approach emphasizes tailoring evaluation to the patient's preceding clinical trajectory, realistically available treatment options, patient preferences (including goals of care), and estimated prognosis; a more comprehensive workup may be warranted for lung transplant candidates, while evaluation should be streamlined for patients ineligible for transplant or prioritizing comfort-focused care.

The document notes that no validated tools predict AE-fILD and no multivariable prognostic models have been validated prospectively. The specificity of GGO for DAD is uncertain and likely lower in non-IPF fILD than in IPF. There is no established consensus on the optimal adjudication process for AE as a clinical trial endpoint, and discrepancies exist between centrally adjudicated and investigator-reported events (central adjudication resulted in a 40% reduction in confirmed or suspected AEs). Additionally, the clinical impact and mortality risk of non-AE ARW need better definition, and whether mechanisms differ between IPF and non-IPF fILD remains to be clarified.