What are the current guidelines for diagnosing and treating interstitial lung disease, including HRCT imaging, multidisciplinary review, antifibrotic therapy for idiopathic pulmonary fibrosis, and steroid‑based regimens for inflammatory or connective‑tissue‑related ILD?

Interstitial Lung Disease Guidelines

Diagnostic Approach

HRCT is the gold standard for ILD diagnosis and must be performed in all patients with suspected ILD, even when asymptomatic, as it has 95.7% sensitivity for detecting disease with ≥20% lung involvement. 1, 2

Initial Clinical Evaluation

• Document comprehensive environmental and occupational exposures (mold, air pollution, vapors, gases, dusts, fumes), as these interact with genetic susceptibility to drive ILD development 2
• Obtain detailed family history of pulmonary fibrosis, as 15-30% of first-degree relatives of patients with familial pulmonary fibrosis exhibit interstitial lung abnormalities 2
• Assess for connective tissue disease features systematically, as CTD accounts for 25% of all ILD cases 3, 4
• Auscultate for fine, dry "Velcro-type" end-inspiratory crackles, present in >80% of IPF patients, though sensitivity is only moderate for early disease 1, 2
• Note that up to 90% of patients with early RA-ILD confirmed on HRCT do not have dyspnea or cough, so absence of symptoms does not exclude disease 1

Pulmonary Function Testing

• Perform spirometry to identify restrictive pattern (decreased FVC) 2
• Measure total lung capacity (TLC) to confirm restriction 2
• Test diffusion capacity (DLCO), which is the most sensitive functional parameter for early ILD detection 2
• Conduct 6-minute walk test with pulse oximetry to evaluate exercise capacity and oxygen desaturation 1, 2
• Recognize that baseline FVC <80% has only 47.5% sensitivity for detecting ILD, emphasizing the primacy of imaging 2

Laboratory Evaluation

• Order complete blood count with differential, C-reactive protein, serum creatinine, transaminases, gamma-glutamyltransferase, and alkaline phosphatases 2
• Test autoimmune serologies including anti-nuclear antibodies, anti-citrullinated cyclic peptide antibodies, and rheumatoid factor 2
• Do NOT routinely measure serum biomarkers (MMP-7, surfactant protein D, CCL-18, KL-6) for differentiating IPF from other ILDs 2

HRCT Imaging Protocol and Interpretation

HRCT should include inspiratory prone images and supine end-expiratory imaging, with slice thickness ≤2 mm and axial contiguous or non-reconstructed slices separated by ≤2 cm. 1, 2

Usual Interstitial Pneumonia (UIP) Pattern

• Subpleural reticulation, traction bronchiectasis, honeycombing, and basal-peripheral distribution 2
• Honeycombing is required to consider a definite UIP pattern on HRCT 1

Non-Specific Interstitial Pneumonia (NSIP) Pattern

• Ground-glass opacities with reticulation and more uniform distribution 2
• Most common pattern in systemic sclerosis-ILD 5

Features Inconsistent with UIP

• Prominent and diffuse ground-glass attenuation 1
• Ground-glass attenuation with mosaic distribution 1

Tissue Diagnosis Strategy

When HRCT shows a definite UIP pattern in the appropriate clinical context, surgical lung biopsy, transbronchial biopsy, or cryobiopsy is NOT indicated. 1, 2

For patients with probable UIP, indeterminate for UIP, or alternative diagnosis patterns on HRCT, transbronchial lung cryobiopsy (TBLC) is suggested as first-line biopsy method because it provides larger specimens without crush artifacts and has lower complication rates than surgical lung biopsy (17.2% unclassifiable rate vs 1.3% for surgical biopsy). 2

Surgical lung biopsy via VATS should be reserved for rapidly progressive ILD or when TBLC yields nondiagnostic results. 2

Bronchoalveolar Lavage Diagnostic Thresholds

• Lymphocyte count >25% suggests granulomatous diseases (sarcoidosis, hypersensitivity pneumonitis), cellular NSIP, drug-induced lung injury, or cryptogenic organizing pneumonia 2
• Lymphocyte count >50% strongly points toward hypersensitivity pneumonitis or cellular NSIP 2
• Eosinophil count >25% is virtually diagnostic of acute or chronic eosinophilic pneumonia 2
• CD4+/CD8- ratio >4 is highly specific for sarcoidosis when other inflammatory cells are not markedly increased 2
• BAL cellular analysis is NOT recommended in patients with a UIP pattern on HRCT 2

Multidisciplinary Discussion (MDD)

Multidisciplinary discussion involving pulmonologists, radiologists, and pathologists experienced in ILD is mandatory for optimal diagnostic accuracy and should integrate clinical, radiological, and pathological findings. 1, 2

The MDD categorizes diagnostic confidence into four tiers:

1. Confident diagnosis (>90% certainty)
2. Provisional diagnosis, high confidence (70-90% certainty)
3. Provisional diagnosis, low confidence (50-70% certainty)
4. Unclassifiable ILD (<50% certainty) 2

Complex cases should be referred to expert centers (reference or competence centers) or pulmonology departments experienced in ILDs. 1

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Management of Idiopathic Pulmonary Fibrosis (IPF)

Antifibrotic therapy with nintedanib or pirfenidone should be started at the time of diagnosis, as both reduce annual FVC decline by approximately 44-57%. 2, 3

Both nintedanib and pirfenidone have comparable efficacy in slowing disease progression. 2

Therapies to AVOID in IPF

Do NOT initiate triple therapy with prednisone, azathioprine, and N-acetylcysteine in patients with definite IPF diagnosis. 1

Prognostic Assessment

Assess prognosis at diagnosis based on:

• Severity of dyspnea 1
• FVC and DLCO results 1
• Percutaneous oxygen saturation at end of 6-minute walk test 1
• Extent of honeycombing on HRCT 1
• Signs of pulmonary hypertension at echocardiography 1
• GAP score (gender, age, physiology) based on age, sex, FVC, and DLCO 1

A 5% decline in FVC over 12 months is associated with approximately 2-fold increase in mortality compared with no change in FVC. 3

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Management of Connective Tissue Disease-Associated ILD (CTD-ILD)

Systemic Sclerosis-ILD (SSc-ILD)

All patients with systemic sclerosis should undergo HRCT screening for ILD at diagnosis, regardless of symptoms, as SSc-ILD is the leading cause of death and has highest prevalence in the first 5 years of disease. 5

Avoid glucocorticoids as first-line treatment in SSc-ILD (strong recommendation against). 2

Tocilizumab is conditionally recommended as first-line option for SSc-ILD and mixed connective tissue disease-ILD. 2

Nintedanib is conditionally recommended for SSc-ILD. 2

Other CTD-ILD (Excluding SSc-ILD)

For most CTD-ILD patients, consider mycophenolate, azathioprine, rituximab, or cyclophosphamide as first-line treatment options. 2

JAK inhibitors and calcineurin inhibitors are conditionally recommended for idiopathic inflammatory myopathy-ILD. 2

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Progressive Pulmonary Fibrosis (PPF)

PPF is defined by at least TWO of the following within 12 months without alternative explanation:

1. Worsening respiratory symptoms
2. Absolute FVC decline >5% predicted OR absolute DLCO decline >10% predicted
3. Radiological evidence of progression (increased traction bronchiectasis, new ground-glass opacities, new honeycombing, increased extent/thickness of reticular abnormality) 1, 2

Antifibrotic therapy with nintedanib or pirfenidone is recommended for progressive fibrosing ILD regardless of the underlying ILD subtype. 2

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Non-Pharmacologic Interventions

Structured pulmonary rehabilitation improves 6-minute walk distance and health-related quality of life. 2, 3

Supplemental oxygen for patients desaturating <88% during 6-minute walk reduces dyspnea and enhances quality of life. 2

Smoking cessation using combined pharmacotherapy (nicotine replacement, varenicline, or bupropion) and behavioral support is the single most effective intervention to slow ILD progression. 2

Age-appropriate vaccinations (influenza and pneumococcal) are recommended to lower risk of respiratory infections that can exacerbate ILD. 2

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Monitoring and Follow-Up

Patients should be evaluated every 3-6 months during the first year after diagnosis to detect disease progression. 2

Serial PFTs (spirometry and DLCO) should be performed every 3-6 months initially, then annually if stable. 1, 2

Follow-up HRCT is recommended 2-3 years after baseline scan to assess radiologic progression. 2

In high-risk patients (definite fibrosis, subpleural fibrotic pattern, extensive radiographic abnormalities, abnormal PFTs, family history of fibrosis, older age, or smoking history), perform earlier HRCT at 12 months. 2

For SSc-ILD high-risk patients, perform PFTs every 6 months and annual HRCT for the first 3-4 years of SSc diagnosis. 5

Echocardiography should be performed annually to screen for pulmonary hypertension, especially with isolated low DLCO. 5

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Comorbidity Management

Systematically evaluate and treat gastroesophageal reflux disease, obstructive sleep apnea, and screen for lung cancer as part of ILD management. 2

Routine echocardiography is strongly recommended in initial work-up to identify structural cardiac or vascular anomalies, as pulmonary hypertension is associated with worse prognosis. 2

Up to 85% of individuals with end-stage fibrotic ILD develop pulmonary hypertension; in these patients, treatment with inhaled treprostinil improves walking distance and respiratory symptoms. 3

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Acute Exacerbations and Advanced Disease

Acute exacerbations of ILD are treated with systemic corticosteroids. 2

Routine invasive mechanical ventilation is NOT recommended for most patients with respiratory failure due to ILD. 2

Patients with elevated risk of mortality should be referred for lung transplantation at the time of diagnosis. 2

After lung transplant, patients with ILD have median survival of 5.2-6.7 years compared with median survival of less than 2 years in patients with advanced ILD who do not undergo transplant. 3

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Critical Pitfalls to Avoid

Do not attribute cough and dyspnea solely to ILD without excluding cardiac disease, asthma, and postnasal drainage. 2

Do not dismiss bilateral lower lobe interstitial changes as clinically insignificant even in asymptomatic patients, as interstitial lung abnormalities are associated with 66% increased risk of death and progression risk regardless of symptoms. 2

Chest radiography alone is insufficient; up to 10% of ILD patients have normal chest X-rays. 2, 5

Bronchoscopy, surgical lung biopsy, or cryobiopsy are NOT recommended for CTD-ILD diagnosis according to expert consensus and ACR guidelines. 1, 5