What is the recommended screening protocol for patients at risk for interstitial lung disease, including those with connective‑tissue disease, occupational or environmental exposures, or prior radiation, using history, physical examination, pulmonary function testing (spirometry and diffusing capacity for carbon monoxide) and high‑resolution computed tomography?

Screening for Interstitial Lung Disease

For patients at increased risk of ILD—particularly those with connective tissue diseases (systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myopathies, mixed connective tissue disease, Sjögren syndrome)—screen with both high-resolution CT chest and pulmonary function testing (spirometry, lung volumes, and DLCO) rather than either modality alone. 1

Who Requires Screening

High-Risk Populations Requiring Systematic Screening

• Most patients with systemic sclerosis (SSc) warrant screening given the 50% prevalence of ILD and 31% contribution to all CTD-ILD cases 2
• Many patients with idiopathic inflammatory myopathies (IIM) require screening, particularly those with anti-MDA-5, anti-synthetase, or overlap antibodies (PM-Scl, Ku, Ro52) 1
• Selected patients with rheumatoid arthritis (RA) who have high-titer anti-CCP or rheumatoid factor positivity, despite RA accounting for 39% of CTD-ILD cases, only 3-5% develop clinically significant progressive ILD 1, 2
• Selected patients with Sjögren syndrome (SjD) based on individual risk assessment—not all require screening 1
• Patients with mixed connective tissue disease (MCTD) at increased risk 1
• Adults ≥50 years with first-degree relative with familial pulmonary fibrosis 1
• Patients undergoing lung cancer screening should have systematic assessment for ILAs/ILD 1

Risk Stratification Within CTD Populations

Screening must be tailored based on disease-specific risk factors 1:

• SSc-ILD: Early diffuse cutaneous disease and/or Scl-70 positivity indicates higher progression risk 1
• RA-ILD: High-titer anti-CCP or rheumatoid factor positivity increases risk 1
• IIM-ILD: Anti-MDA-5, anti-synthetase, or overlap antibodies (PM-Scl, Ku, Ro52) confer increased progression risk 1

Recommended Screening Protocol

Primary Screening Modalities

Combine HRCT chest with comprehensive pulmonary function testing 1:

• HRCT chest demonstrates 95.7% sensitivity and 63.8% specificity for detecting ILD (≥20% lung involvement) 1, 2
• PFTs alone are insufficient: FVC <80% has only 47.5% sensitivity and 78.7% specificity, while HRCT has 100% sensitivity and 55.3% specificity 1
• The combination provides complementary information: HRCT shows presence and pattern of ILD, while PFTs demonstrate physiologic impact 2

Technical HRCT Specifications

Obtain volumetric HRCT with specific acquisition parameters 2:

• Slice thickness ≤1.5 mm on full inspiration 2
• Inspiratory prone images to differentiate mild dependent atelectasis from early fibrosis 1, 2
• Supine end-expiratory imaging to assess for air-trapping 1, 2
• Low-dose technique without contrast is adequate for ILD detection 1

Critical pitfall: CT angiogram studies are inadequate for ILD assessment because they are performed in incomplete inspiration, producing atelectasis that can obscure, accentuate, or mimic ILD 1

Comprehensive Pulmonary Function Testing

PFTs must include all three components 1:

• Spirometry (FVC, FEV1) 1
• Lung volumes (TLC) 1
• Diffusing capacity for carbon monoxide (DLCO) 1

DLCO <80% demonstrates 83.6% sensitivity but only 45.8% specificity for ILD detection 3

The combination of reduced DLCO, chest X-ray, and HRCT yields 95.2% sensitivity and 77.4% specificity 3

History and Physical Examination Components

While history and physical examination alone are inadequate for screening, specific findings warrant immediate further evaluation 1:

• Progressive dyspnea on exertion >6 months is the most prominent symptom 2
• Nonproductive cough occurs in 40-50% of patients, may be paroxysmal, dry, and refractory to antitussives 2
• "Velcro" crackles on lung auscultation are detected in >80% of ILD patients (69% sensitive, 66% specific) 1, 2
• Clubbing is noted in 25-50% of patients with progressive involvement 2
• Raynaud's phenomenon is common, particularly in MCTD and systemic sclerosis 2

History alone demonstrates poor diagnostic accuracy: dry cough is only 15% sensitive and 89% specific 1

Physical examination alone is inadequate: dry "velcro" crackles are 69% sensitive and 66% specific 1

Modalities to Avoid for Screening

The following modalities are NOT recommended for ILD screening 1:

• Chest radiography: Conditionally recommend against 1
• 6-minute walk distance (6MWD): Conditionally recommend against 1
• Ambulatory desaturation testing alone: Conditionally recommend against 1
• Bronchoscopy: Conditionally recommend against 1
• Surgical lung biopsy: Strongly recommend against for screening purposes 1

Stepwise Screening Algorithm for Resource-Limited Settings

When comprehensive screening is not immediately feasible, use a stepwise approach 3:

1. Initial assessment: DLCO and chest radiography 3
2. If either is abnormal: Proceed to HRCT chest 3
3. This stepwise approach achieves 95.2% sensitivity and 77.4% specificity 3

Additional Diagnostic Considerations

Serologic Evaluation

When ILD is detected without known CTD, perform autoimmune panel 2:

• ANA by indirect immunofluorescence as initial screening 4
• Disease-specific antibodies based on clinical presentation: anti-Scl-70, anti-centromere, anti-RNA polymerase III for SSc; anti-CCP and RF for RA; anti-synthetase antibodies and anti-MDA-5 for IIM; anti-SSA/Ro and anti-SSB/La for Sjögren syndrome 4

Occupational and Environmental Exposures

Systematically assess exposure history using standardized questionnaires 2, 5:

• Occupational dust exposures (silica, asbestos) 5
• Organic antigen exposures (hypersensitivity pneumonitis) 5
• Prior tuberculosis or endemic fungal exposures 6
• Medication exposures 1

Critical Pitfalls to Avoid

• Do not delay screening in known SARD patients: Irreversible lung function loss can occur asymptomatically 2
• Do not rely on PFTs alone: Patients with ILD can have normal PFTs or difficulty performing them due to cough or microstomia 1, 2
• Do not dismiss nonspecific symptoms: Fatigue, mild dyspnea, or arthralgias may represent early but irreversible organ damage 2
• Do not use history and physical examination as sole screening tools: They lack adequate sensitivity and specificity 1
• Do not assume negative autoantibodies exclude disease progression, especially early in disease course 2
• Maintain high clinical suspicion even when systemic symptoms appear mild, particularly in the first 5-7 years after disease onset 2