Managing Acute Exacerbations in Fibrotic Interstitial Lung Disease in the Hospitalized Patient

In this episode of Hospital Medicine Unplugged, we sprint through acute exacerbation of interstitial lung disease (AE-ILD)—recognize the sudden decline, rule out infection and cardiac causes, support oxygenation, and navigate a disease with limited treatment options and high mortality. We begin with the diagnostic framework defined by the 2016 International Working Group. Acute exacerbation is characterized by rapid respiratory deterioration within about 1 month, accompanied by new bilateral ground-glass opacities or consolidation on CT superimposed on pre-existing fibrotic lung disease, with no evidence of cardiac failure or fluid overload. Importantly, this definition now applies across fibrosing interstitial lung diseases, not just idiopathic pulmonary fibrosis (IPF). The critical bedside principle: AE-ILD is a diagnosis of exclusion. Infection, pulmonary embolism, pneumothorax, and heart failure must be aggressively ruled out because they can mimic exacerbations and require completely different management. Next, we turn to pathobiology and why these patients deteriorate so rapidly. Acute exacerbations often represent diffuse alveolar damage superimposed on chronic fibrosis, producing a clinical picture similar to ARDS. However, in some non-IPF ILDs, organizing pneumonia patterns are more common—one reason those patients may respond better to immunosuppressive therapy. Treatment remains challenging because no therapy has definitively proven benefit in randomized trials. Corticosteroids remain the most widely used intervention, but evidence is mixed. Recent data suggest a key difference between ILD subtypes. In non-IPF ILD, higher-dose corticosteroids (>1 mg/kg prednisone equivalent) have been associated with improved survival and lower 90-day mortality. Early tapering—reducing doses by more than 10% within the first two weeks—may further improve outcomes. In contrast, IPF exacerbations respond less predictably, and some studies suggest high-dose steroids may increase mortality, likely because the underlying pathology is often diffuse alveolar damage rather than steroid-responsive inflammation. One therapy that should not be used is cyclophosphamide combined with steroids, which has been shown to increase mortality in acute exacerbations of IPF. Respiratory support becomes the next critical decision point. Many patients develop severe hypoxemic respiratory failure, but outcomes with invasive mechanical ventilation are poor. Across multiple studies: • In-hospital mortality ranges from 66–79% in ventilated ILD patients • Only ~20% of ventilated IPF patients survive to hospital discharge Ventilator management therefore focuses on lung-protective strategies, similar to ARDS care: • Low tidal volumes • Plateau pressures ≤30 cm H₂O • Avoid excessive PEEP, which has been associated with worse outcomes • Careful fluid management to prevent worsening pulmonary edema Because survival after intubation is so limited, early discussions about goals of care are essential. Noninvasive ventilation or high-flow nasal oxygen may be appropriate for selected patients who decline intubation. Prevention is therefore critically important. Antifibrotic therapies have significantly reduced exacerbation risk in IPF. Two major agents are used: • Nintedanib – shown in the INPULSIS trials to reduce the risk of acute exacerbations • Pirfenidone – also associated with lower exacerbation rates in multiple studies Meta-analyses show antifibrotics reduce the risk of acute exacerbations by roughly 37%, and nintedanib has also been approved for progressive fibrosing ILDs beyond IPF, after the INBUILD trial demonstrated substantial slowing of lung function decline. New therapies are also emerging. The FIBRONEER-ILD trial studied nerandomilast, a novel PDE-4 inhibitor, and although the composite endpoint did not reach statistical significance, the study demonstrated a meaningful reduction in mortality, suggesting a potential future role in progressive pulmonary fibrosis. Another key strategy is early referral for lung transplantation, particularly in patients with progressive fibrotic disease. Acute exacerbations can occur unpredictably and often represent a terminal event in advanced ILD, making transplant evaluation crucial before severe deterioration occurs. We close with the key system moves for inpatient teams: • Recognize sudden respiratory decline in patients with fibrotic lung disease • Confirm new bilateral ground-glass opacities on CT • Aggressively rule out infection, pulmonary embolism, and heart failure • Consider corticosteroids, particularly in non-IPF ILD • Use lung-protective ventilation if respiratory failure develops • Discuss prognosis early and involve palliative care • Ensure patients with fibrotic ILD are on antifibrotic therapy when appropriate Acute exacerbation of ILD remains one of the most devastating events in pulmonary medicine—but early recognition, careful ...