What is the step-by-step management of interstitial lung disease?

Step-by-Step Management of Interstitial Lung Disease

The management of ILD requires an algorithmic approach beginning with multidisciplinary diagnosis integrating HRCT, pulmonary function testing, and clinical assessment, followed by disease-specific treatment with antifibrotics for IPF/progressive fibrosis or immunosuppression for connective tissue disease-associated ILD. 1

Step 1: Establish Definitive Diagnosis Through Multidisciplinary Discussion

• Convene a multidisciplinary discussion (MDD) involving pulmonologists, radiologists, and pathologists to integrate clinical, radiological, and pathological data—this is mandatory for optimal diagnostic accuracy and improves outcomes. 1, 2

• Obtain high-resolution CT (HRCT) as the gold standard imaging test, which achieves 95.7% sensitivity for detecting ILD involving ≥20% of lung parenchyma. 1

• Perform complete pulmonary function testing including spirometry (FVC), total lung capacity (TLC), and diffusion capacity (DLCO)—DLCO is the most sensitive early marker of ILD. 1

• Document detailed environmental and occupational exposure history (mold, air pollution, organic antigens, silica, asbestos) and assess for connective tissue disease through autoimmune serologies (ANA, rheumatoid factor, anti-CCP, anti-Scl-70, anti-Jo-1, myositis-specific antibodies). 1, 3

• When HRCT shows definite UIP pattern in appropriate clinical context, do NOT perform surgical lung biopsy, transbronchial biopsy, or cryobiopsy—tissue diagnosis is not indicated. 1

• If tissue diagnosis is needed, transbronchial lung cryobiopsy (TBLC) is the first-line biopsy method because it provides larger specimens with fewer crush artifacts and lower complication rates than surgical biopsy (17.2% vs 1.3% unclassifiable rate). 1

Step 2: Classify ILD Subtype to Guide Treatment Strategy

The fundamental treatment decision hinges on whether ILD is inflammatory (requiring immunosuppression) versus fibrotic (requiring antifibrotic therapy). 3

For Idiopathic Pulmonary Fibrosis (IPF):

• Diagnosed by definite UIP pattern on HRCT (subpleural reticulation, traction bronchiectasis, honeycombing, basal-peripheral distribution) in patients typically >50 years, male smokers, without CTD. 1

For Connective Tissue Disease-Associated ILD (CTD-ILD):

• Accounts for 25% of all ILD cases and includes rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren syndrome. 1, 4

For Progressive Pulmonary Fibrosis (PPF):

• Defined by at least two of the following within 12 months: (1) worsening respiratory symptoms, (2) absolute FVC decline >5% predicted OR absolute DLCO decline >10% predicted, (3) radiological progression (increased traction bronchiectasis, new ground-glass opacities, new honeycombing, increased reticular abnormality). 1

Step 3: Initiate Disease-Specific First-Line Therapy

For IPF with Definite UIP Pattern:

Start antifibrotic therapy with either nintedanib or pirfenidone at the time of diagnosis—both reduce annual FVC decline by 44-57% and have comparable efficacy. 1, 4

• Do NOT use triple therapy (prednisone + azathioprine + N-acetylcysteine)—this is strongly contraindicated in IPF and increases mortality. 1

• Do NOT use immunosuppressive therapy in IPF—it is ineffective and potentially harmful. 3

For Connective Tissue Disease-Associated ILD:

Mycophenolate is the preferred first-line immunosuppressive agent for all SARD-ILD subtypes, including those with UIP pattern. 5, 3, 1

Alternative first-line options (all conditionally recommended):

• Rituximab for all SARD-ILD subtypes 5
• Azathioprine for most SARD-ILD except systemic sclerosis 5
• Cyclophosphamide as monotherapy (not combined with other agents) 5, 3

Disease-Specific Considerations:

For Systemic Sclerosis-ILD:

• Strongly avoid glucocorticoids as first-line therapy due to risk of scleroderma renal crisis, especially at doses >15mg/day prednisone equivalent. 5, 3
• Conditionally recommend tocilizumab and nintedanib as additional first-line options. 5

For Idiopathic Inflammatory Myopathy-ILD:

• Conditionally recommend JAK inhibitors and calcineurin inhibitors as first-line options. 5

For Other CTD-ILD (not SSc):

• Short-term glucocorticoids (≤3 months) are conditionally recommended during flares or as a bridge when switching agents. 3

For Progressive Pulmonary Fibrosis (Any Cause):

Antifibrotic therapy with nintedanib or pirfenidone is recommended regardless of underlying ILD subtype. 1, 4

Step 4: Manage Rapidly Progressive ILD (RP-ILD)

For RP-ILD, pulse intravenous methylprednisolone is conditionally recommended as first-line treatment. 5

• Upfront combination therapy is preferred over monotherapy for RP-ILD. 5

• Additional first-line options include rituximab, cyclophosphamide, IVIG, mycophenolate, calcineurin inhibitors, and JAK inhibitors. 5

• Early referral for lung transplantation is recommended over delayed referral. 5

Step 5: Implement Non-Pharmacologic Interventions

• Structured pulmonary rehabilitation improves 6-minute walk distance and quality of life. 1, 4

• Supplemental oxygen for patients desaturating <88% during 6-minute walk test reduces dyspnea and improves quality of life. 1

• Smoking cessation using combined pharmacotherapy (nicotine replacement, varenicline, or bupropion) and behavioral support is the single most effective intervention to slow progression. 1

• Age-appropriate vaccinations (influenza and pneumococcal) reduce risk of respiratory infections that exacerbate ILD. 1

Step 6: Establish Monitoring Protocol

Serial pulmonary function tests (spirometry and DLCO) every 3-6 months during the first year, then annually if stable. 1

• A 5% decline in FVC over 12 months is associated with approximately 2-fold increase in mortality compared to no change. 4

• Follow-up HRCT at 2-3 years after baseline to assess radiologic progression. 1

• Earlier HRCT at 12 months for high-risk patients (definite fibrosis, extensive radiographic abnormalities, abnormal PFTs, family history of fibrosis, older age, smoking history). 1

• Ambulatory desaturation testing every 3-12 months for monitoring. 1

Step 7: Manage Disease Progression

If Progressive Pulmonary Fibrosis Develops on First-Line Therapy:

For SARD-ILD with PPF, add nintedanib to ongoing immunosuppressive therapy rather than switching immunosuppression. 5, 3

• Alternative options for progressive SARD-ILD include mycophenolate, rituximab, cyclophosphamide, and nintedanib. 5

• For RA-ILD progression, conditionally add pirfenidone. 5

• For SSc-ILD, MCTD-ILD, or RA-ILD progression, conditionally add tocilizumab. 5

• For IIM-ILD progression, conditionally add calcineurin inhibitors or JAK inhibitors. 5

• For SSc-ILD progression, refer for stem cell transplantation and/or lung transplantation. 5

Step 8: Address Comorbidities and Complications

• Systematically evaluate and treat gastroesophageal reflux disease—GERD is a common reversible contributor to cough that must be assessed before attributing symptoms to ILD alone. 1, 3

• Screen for obstructive sleep apnea as part of comprehensive ILD management. 1

• Perform routine echocardiography to identify pulmonary hypertension, which occurs in up to 85% of end-stage fibrotic ILD and is associated with worse prognosis. 1, 4

• Screen for lung cancer annually with HRCT—ILD patients have increased cancer risk. 1

Step 9: Lung Transplant Evaluation

Refer patients with elevated mortality risk for lung transplantation at the time of diagnosis. 1

• After lung transplant, patients with ILD have a median survival of 5.2-6.7 years compared to <2 years without transplant in advanced disease. 4

• Do NOT routinely use invasive mechanical ventilation for most patients with respiratory failure due to ILD—outcomes are poor. 1

Critical Pitfalls to Avoid

• Do not attribute cough and dyspnea solely to ILD without excluding cardiac disease, asthma, and postnasal drainage—these are common alternative or coexisting causes. 1

• Do not dismiss asymptomatic patients—up to 90% of early rheumatoid arthritis-associated ILD patients have no dyspnea or cough. 1

• Do not use leflunomide, methotrexate, TNF-inhibitors, or abatacept as first-line ILD treatments—insufficient efficacy data and potential for harm. 3

• Do not delay immunosuppression while waiting for complete diagnostic workup in SARD-ILD—early treatment prevents irreversible organ damage. 5

• Do not use long-term glucocorticoid monotherapy across all CTD-ILD subtypes—limit to short courses or combine with steroid-sparing agents. 3