Acute Exacerbation in Fibrotic Interstitial Lung Disease: Key Recommendations from the 2026 International Working Group Report

Introduction and Context

Acute exacerbations (AEs) are sudden, clinically significant worsenings of respiratory status that arise in patients with fibrotic interstitial lung disease (fILD). Historically most literature focused on AE in idiopathic pulmonary fibrosis (AE‑IPF). The 2016 international working group provided the first modern operational definition for AE‑IPF, but subsequent data showed that acute, severe deteriorations are common across the wider spectrum of fibrotic ILDs and that prior definitions and study methods limited research and clinical care.

The 2026 International Working Group Report (Khor et al., AJRCCM 2026) updates and expands the framework to all fILDs. It revises diagnostic criteria, introduces the broader concept of acute respiratory worsening (ARW), clarifies recommended evaluation steps, synthesizes limited evidence on management, and lays out priorities for research and clinical trials. This article summarizes the working group’s recommendations and discusses implications for clinicians, researchers, and patients.

New Guideline Highlights

– Revised, generalizable definition: AE‑fILD is now defined as an acute respiratory event in a patient with known or newly diagnosed fibrotic ILD characterized by increased respiratory signs/symptoms and radiologic or histologic evidence consistent with diffuse alveolar damage (DAD) with or without organizing pneumonia.
– Conceptual expansion: ARW is introduced as an umbrella term for heterogeneous acute deteriorations in fILD not attributable to DAD (for example, pulmonary edema, pneumonia, bronchitis), while acknowledging that severe infections can precipitate AE‑fILD.
– Diagnostic approach: Emphasizes high-resolution chest CT (HRCT), targeted microbiologic evaluation (BAL where feasible), careful cardiac assessment to exclude cardiogenic edema, and selective lung biopsy only if results would change management.
– Management principles: Recognizes lack of level‑1 evidence for most interventions. Recommends individualized supportive care, attention to reversible causes, pragmatic use of antimicrobials when infection is suspected, cautious use of systemic corticosteroids (no randomized evidence), continuation or early initiation of antifibrotic therapy when appropriate, and early goals‑of‑care discussions.
– Research and trials: Calls for standardized AE‑fILD diagnostic criteria in trials, harmonized reporting of suspected vs. definite AEs, and prioritized research into biomarkers, prevention, and randomized therapeutic trials.

Key takeaways for clinicians
– Think AE‑fILD when a patient with fibrotic ILD has rapid worsening and new bilateral ground‑glass opacities on CT not fully explained by heart failure or volume overload.
– Distinguish AE‑fILD from other causes of ARW because management and prognosis differ.
– Use bronchoscopy/BAL selectively to exclude infection; rely on a structured multi‑disciplinary evaluation.
– Antifibrotic therapy may lower AE risk in some fILDs — do not routinely stop it during an AE unless clear contraindication.

Updated Recommendations and Key Changes from 2016

Bulleted comparison (2016 → 2026):
– Definition scope: AE‑IPF (2016) → AE‑fILD (2026): broadened to include non‑IPF fibrotic ILDs.
– Diagnostic criteria: Earlier criteria focused on idiopathic etiology and excluded infection more rigidly; the 2026 report allows for DAD to be present with or without an identifiable trigger and recognizes infection may coexist.
– New construct: ARW introduced (no analogue in 2016), improving clinical categorization of acute deteriorations.
– Trial endpoints: 2026 report provides concrete recommendations for capturing AE events in clinical trials and for classifying definite vs suspected AE to improve comparability across studies.

Evidence driving updates
– Accumulating observational data show AE‑type events occur in connective tissue disease‑associated ILD, chronic hypersensitivity pneumonitis, and other fibrotic ILDs with similar clinicopathologic features and outcomes to AE‑IPF.
– Increasing use and evidence for antifibrotic drugs across progressive fibrosing ILDs (e.g., INBUILD and other trials) prompted consideration of AE prevention and incorporation into trial designs.

Topic-by-Topic Recommendations

Definition and diagnostic criteria (core recommendation):
– AE‑fILD is an acute respiratory event (typically days–weeks) with:
– Increased dyspnea, hypoxemia, or respiratory distress beyond usual day‑to‑day variability; and
– New bilateral radiologic abnormalities (ground‑glass opacities and/or consolidation) superimposed on background fibrotic changes on HRCT; and
– Radiologic and/or histologic features consistent with diffuse alveolar damage (with or without organizing pneumonia).
– AE‑fILD may be triggered (infection, aspiration, procedures) or idiopathic; the presence of a trigger does not exclude the diagnosis when DAD is present.

Acute respiratory worsening (ARW):
– ARW is a broader category that includes acute deteriorations not due to DAD (e.g., cardiogenic pulmonary edema, uncontrolled pleural effusion, acute pulmonary embolism, focal infection). The working group recommends structured evaluation to classify events as AE‑fILD versus ARW.

Diagnostic evaluation (recommendations):
– Immediate assessment: oxygenation status, chest radiograph/HRCT, basic labs (CBC, BNP), and assessment for heart failure or volume overload.
– HRCT: central to identifying new diffuse opacities on a background of fibrosis.
– Bronchoscopy with bronchoalveolar lavage (BAL): recommended when infection is suspected and when results will alter therapy; early sampling increases diagnostic yield.
– Microbiologic testing: obtain sputum cultures, viral PCRs, and consider pneumocystis PCR if immunosuppressed.
– Echocardiography: evaluate left heart function to exclude cardiogenic causes.
– Lung biopsy: reserved for atypical cases where diagnosis is unclear and biopsy would change management; invasive procedures carry high risk in the setting of respiratory failure.

Management (evidence‑based but limited):
– Supportive care: high‑flow oxygen, titrated ventilation support when needed, thromboprophylaxis, and organ support per ICU standards.
– Antimicrobials: empirical antibiotics informed by clinical context if infection is suspected; de‑escalate based on results.
– Systemic corticosteroids: frequently used in practice for AE‑IPF/fILD but lacks randomized controlled trial evidence; the report endorses cautious, individualized use and calls for trials to evaluate efficacy and dosing.
– Immunosuppressive therapy beyond steroids: the committee does not recommend routine use of broad immunosuppression (e.g., cyclophosphamide) outside clinical trials due to limited and conflicting evidence.
– Antifibrotic therapy (nintedanib/pirfenidone): generally continue in patients already receiving therapy unless contraindicated; consider initiation after stabilization in appropriate progressive fILD patients, with attention to interactions and tolerability. Observational and randomized trial signals suggest antifibrotics may reduce AE rates in some contexts (e.g., nintedanib in IPF and progressive fibrosing ILDs).
– Mechanical ventilation and ECMO: discuss prognosis and goals of care early; invasive mechanical ventilation is associated with poor outcomes in AE‑fILD and should be considered carefully; ECMO may be reasonable as a bridge to transplantation in selected candidates.

Follow‑up and post‑AE care:
– Reassess disease status after recovery, optimize chronic ILD care (antifibrotics, immunomodulation based on ILD subtype), and review transplant candidacy where appropriate.
– Offer pulmonary rehabilitation and early palliative care involvement for symptom management and advance care planning.

Special populations and perioperative considerations:
– Non‑IPF fibrotic ILDs: approach similar—evaluate for DAD and reversible causes; prognosis varies by underlying disease.
– Postoperative risk: consider perioperative optimization because thoracic surgery and procedures can precipitate AE.
– Transplant candidates: AE may accelerate listing and require urgent evaluation for transplant suitability; outcomes depend on center practices and pre‑AE listing status.

Expert Commentary and Insights

Consensus views
– The working group emphasized harmonization: using a single, radiologic/histologic‑anchored definition across fILDs improves research comparability and clinical clarity.
– There is broad agreement that the traditional insistence on excluding all infections before diagnosing AE is unrealistic; severe infection may coexist with DAD, and detection should not automatically exclude the AE diagnosis if DAD is present.

Controversies and areas lacking consensus
– Steroids: experts divided. Many clinicians use moderate‑to‑high‑dose corticosteroids empirically, supported by pathophysiologic rationale and observational reports, while others worry about infectious complications and lack of randomized evidence.
– Role of additional immunosuppression (cyclophosphamide, tacrolimus) remains contentious due to conflicting data and safety concerns.
– Antifibrotic timing: while there is increasing support to continue antifibrotics during AE, high‑quality evidence specifically addressing initiation during or immediately after AE is limited.

Key expert quotes (paraphrased)
– “Standardized definitions and systematic collection will be the most important immediate advance — without that, trials and biomarker studies cannot be compared.”
– “We cannot avoid steroids entirely in practice, but we must do better clinical trials to inform dose and duration.”

Practical Implications

For clinicians
– Implement the revised AE‑fILD definition in clinical notes and multidisciplinary discussions.
– Use a stepwise diagnostic algorithm: HRCT → evaluate for cardiac causes → targeted microbiologic testing (BAL if necessary) → selective histology.
– Keep patients and families informed: the prognosis of AE‑fILD is often poor; early goals‑of‑care conversations are essential.

For researchers and trialists
– Use the 2026 harmonized criteria to define AE endpoints, and distinguish definite vs suspected events in trial protocols.
– Prioritize trials on corticosteroids, antifibrotic strategies in the acute setting, and targeted immunomodulators.

Healthcare systems
– Ensure pathways exist for rapid multidisciplinary evaluation of acute deteriorations in ILD centers, including access to HRCT, BAL, and critical care resources.

Patient vignette (illustrative)
– Mary, a 68‑year‑old woman with known post‑radiation fibrotic ILD, presents with 7 days of progressive dyspnea and new hypoxemia. HRCT shows new bilateral ground‑glass opacities superimposed on established fibrosis. BNP is normal; echocardiography shows preserved LV function. BAL is performed and cultures pending. The team diagnoses AE‑fILD per the new definition, starts supplemental oxygen and empiric antibiotics while considering a short steroid course after multidisciplinary discussion, continues her antifibrotic, and urgently reviews transplant status given her oxygen requirement.

Research Priorities Identified by the Working Group

– Biomarkers (blood, BAL, imaging) to predict, detect, and prognosticate AE events.
– Randomized trials of corticosteroid strategies and of adjunctive immunomodulators in AE‑fILD.
– Trials of antifibrotic initiation/continuation strategies in the acute setting.
– Mechanistic studies to define triggers (infection, aspiration, mechanical stress) and pathways leading to DAD.
– Standardized AE reporting and multicenter registries to improve event capture and outcomes research.

References

1) Khor YH, Luppi F, Adegunsoye A, et al. Acute exacerbation in fibrotic interstitial lung disease: An International Working Group Report. Am J Respir Crit Care Med. 2026 Jul 14. PMID: 42447235.
2) Collard HR, Ryerson CJ, Corte TJ, et al. Acute exacerbation of idiopathic pulmonary fibrosis: an international working group report. Am J Respir Crit Care Med. 2016;194(3):265‑275.
3) Raghu G, Remy‑Jardin M, Myers JL, et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018;198(5):e44‑e68.
4) Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381:1718‑1727. (INBUILD trial)
5) Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071‑2082.
6) King TE Jr, Bradford WZ, Castro‑Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083‑2092.

The 2026 International Working Group Report represents an important step toward harmonizing how clinicians and investigators approach acute respiratory deteriorations in fibrotic ILDs. By broadening the definition, introducing the ARW framework, and providing pragmatic diagnostic and management guidance while spotlighting research needs, the report should improve consistency of care and accelerate trials that can answer the pressing therapeutic questions clinicians face at the bedside.