What is the management approach for a patient with an acute exacerbation of interstitial lung disease (ILD)?

Management of Acute ILD Exacerbation

For acute exacerbations of interstitial lung disease, immediately initiate high-dose systemic corticosteroids (typically intravenous methylprednisolone up to 1 gram per day or oral prednisone 40 mg daily), provide supplemental oxygen targeting SpO2 88-92%, and consider early referral to a lung transplant center given the high mortality without transplantation. 1, 2

Immediate Assessment and Diagnostic Approach

• Distinguish between acute exacerbation of known ILD versus de novo presentation, as this fundamentally changes your diagnostic and therapeutic approach 3, 2

• For patients with known chronic ILD, investigate both primary causes (true acute exacerbation) and secondary causes including:

  • Concomitant pulmonary infections 3
  • Fluid overload 3
  • Pulmonary embolism 3

• For de novo ILD presentations, perform diagnostic work-up including autoimmune screening, bronchoalveolar lavage, and high-resolution CT chest while simultaneously ruling out reversible causes of acute respiratory failure 3, 2

• Obtain chest radiography and arterial blood gas sampling early, as these are useful diagnostic tests in acute presentations 1

Pharmacological Management

Corticosteroid Therapy

• Administer high-dose systemic corticosteroids as the cornerstone of therapy, despite very low-quality evidence, given the high mortality of untreated acute exacerbation 1

• Intravenous corticosteroids up to 1 gram per day have been reported in case series, though specific dosing, route, and duration recommendations cannot be definitively made from available evidence 1

• The rationale for corticosteroid use places high value on anecdotal reports of benefit balanced against the extremely high mortality of acute exacerbation (often exceeding 50-80% without lung transplantation) 1, 2

Immunosuppressive Therapy

• For rapidly progressive ILD (RP-ILD), particularly in systemic autoimmune rheumatic disease contexts, strongly consider upfront combination therapy rather than monotherapy 1

• Triple therapy combinations (glucocorticoids plus two additional agents) are conditionally recommended for confirmed or suspected MDA-5 associated RP-ILD 1

• Double or triple therapy options are recommended for RP-ILD without confirmed MDA-5, using combinations of glucocorticoids with rituximab, cyclophosphamide, IVIG, tacrolimus, mycophenolate, or JAK inhibitors 1

• Observational studies suggest combination cyclophosphamide, tacrolimus, and glucocorticoids demonstrate beneficial effects on survival compared to sequential step-up approaches in MDA-5-ILD 1

• Adding IVIG to standard immunosuppressive medications in MDA-5 RP-ILD resulted in lower all-cause death rates compared with standard therapy in one study 1

Antibiotic Coverage

• Administer intravenous antibiotics empirically to cover potential infectious triggers, as infection is a common precipitant of acute exacerbation 2

• Antibiotic therapy should be part of the initial management bundle while awaiting culture results 2

Respiratory Support Strategy

Oxygen Supplementation

• Provide supplemental oxygen immediately to correct hypoxemia and control dyspnea 3, 2

• Target oxygen saturation appropriately based on the severity of hypoxemia 2

High-Flow Nasal Cannula (HFNC)

• Consider HFNC as an alternative to conventional oxygen therapy in patients requiring both high flows and high oxygen concentrations 3, 4

• HFNC is well-tolerated in AE-ILD patients with no serious adverse events or patient-requested discontinuations reported in studies 4

• The SpO2/FIO2 ratio at 24 hours after initiating HFNC is a good predictor of successful HFNC treatment, with a ratio ≥170.9 significantly associated with success (odds ratio 51.3) 4

• Approximately 39% of AE-ILD patients show improved oxygenation and successful withdrawal from HFNC 4

Non-Invasive Ventilation (NIV)

• NIV does not appear to change the poor outcomes associated with advanced stages of ILD, but may be considered in selected patients with less severe acute respiratory failure 3

• A NIV trial might help in early recognition of NIV-responder patients who may present better short-term prognosis 3

• NIV should be used cautiously as it has shown limited benefit in altering the exacerbation course unless serving as a bridge to lung transplantation 5, 3

Invasive Mechanical Ventilation (IMV)

• Limit IMV to patients listed for lung transplant or with clearly reversible causes of acute respiratory failure, as outcomes with mechanical ventilation are generally poor without transplantation 5, 3

• IMV should be considered primarily as a bridge to lung transplantation rather than definitive therapy 5, 3

Extracorporeal Membrane Oxygenation (ECMO)

• Reserve ECMO for severe cases as a bridge to lung transplantation in appropriate candidates 2

• ECMO should only be implemented in centers with transplant capabilities and expertise 2

Lung Transplantation Considerations

• Refer early to lung transplant centers given the high mortality rates without transplantation (median survival <2 years in advanced ILD without transplant versus 5.2-6.7 years post-transplant) 6

• The need for high-flow oxygen is a marker of severity warranting transfer to a transplantation center 1

• Early referral is warranted even if not local to the patient, as the pre-transplantation evaluation takes considerable time 1

• Rapidly progressive ILD patients should receive early referral for lung transplantation over later referral after progression on optimal medical management 1

Supportive Care Measures

• Supportive care is the mainstay of therapy alongside pharmacological interventions 1

• Consider pulmonary rehabilitation for patients who stabilize, though this should be tailored to the ILD population 1

• Address comorbid conditions including pulmonary hypertension (present in up to 85% of end-stage fibrotic ILD), gastroesophageal reflux disease, and obesity 1, 6

Critical Pitfalls to Avoid

• Do not delay lung transplant referral in patients with severe acute exacerbation, as the window of opportunity closes rapidly 1, 6

• Avoid using plasma exchange as first-line therapy; reserve it as salvage therapy in refractory cases, and if used, avoid removing rituximab or IVIG through timing of plasma exchange 1

• Do not rely solely on non-invasive ventilation in patients with advanced disease who are not transplant candidates, as outcomes remain poor 3

• Recognize that acute spirometry is not useful during acute exacerbation, unlike chest radiography and arterial blood gas sampling 1

Prognosis and Risk Stratification

• Risk stratification using clinical and radiographic findings is important in ICU care 5

• Early palliative care involvement should be considered given the high mortality rates 5

• The 30-day survival rate in AE-ILD is approximately 48.5%, highlighting the severity of this condition 4

• Admission to ICU is very common and the need for mechanical ventilation arises early in the disease course 5