What is the appropriate workup and management for a patient with suspected restrictive lung disease?

Workup for Restrictive Lung Disease

Begin with spirometry to identify a restrictive pattern (reduced FVC with normal or elevated FEV1/FVC ratio), then immediately proceed to full pulmonary function testing with lung volumes to confirm true restriction (reduced TLC), followed by DLCO measurement and high-resolution chest CT to differentiate intrinsic parenchymal disease from extrapulmonary causes. 1

Initial Diagnostic Steps

Spirometry and Pulmonary Function Testing

• Spirometry alone cannot diagnose restrictive lung disease—it only suggests the pattern when FVC is reduced with FEV1/FVC ≥0.70. 1
• Confirmation requires measurement of total lung capacity (TLC)—a TLC below the lower limit of normal (typically <80% predicted or <-1.96 SD) confirms true restriction. 1, 2
• Measure diffusing capacity for carbon monoxide (DLCO) to assess gas exchange impairment, which helps distinguish parenchymal disease (reduced DLCO) from chest wall/neuromuscular causes (often preserved DLCO). 1, 2

High-Resolution Chest CT (HRCT)

• HRCT is essential for identifying the underlying etiology and should be obtained in all patients with confirmed restriction. 1
• Look for specific patterns: usual interstitial pneumonia (UIP) shows reticulation, traction bronchiectasis, and honeycombing; non-specific interstitial pneumonia (NSIP) shows ground-glass opacities with or without reticulation. 1
• Radiologist-clinician consultation is mandatory for accurate interpretation, as radiological findings must be integrated with clinical context. 1

Comprehensive Clinical Evaluation

Detailed History

• Occupational and environmental exposures: Ask specifically about asbestos, silica, coal dust, organic antigens (birds, mold), and review material safety data sheets if available. 1, 3
• Smoking history: Document pack-years, as this influences differential diagnosis. 1
• Timing of symptoms relative to exposures: Critical for hypersensitivity pneumonitis—use systematic standardized questionnaires. 3
• Connective tissue disease symptoms: Screen for arthritis, skin changes, Raynaud's phenomenon, dry eyes/mouth, muscle weakness, and rashes suggesting rheumatoid arthritis, systemic sclerosis, inflammatory myopathies, or vasculitis. 1, 3
• Respiratory symptom pattern: Non-productive cough and progressive exertional dyspnea are characteristic; note that 90% of patients with early interstitial lung disease may lack dyspnea or cough. 1, 3
• Neuromuscular symptoms: Assess for progressive weakness, orthopnea, morning headaches, and sleep disturbances suggesting neuromuscular disease. 4

Physical Examination

• Auscultate for fine inspiratory crackles (Velcro-like), though sensitivity is only moderate for early disease. 1
• Examine for signs of connective tissue disease: Joint deformities, skin thickening, telangiectasias, muscle atrophy. 1
• Assess for chest wall deformities: Kyphoscoliosis, pectus excavatum. 2, 4
• Look for signs of obesity hypoventilation syndrome: BMI >30 kg/m², peripheral edema, elevated serum bicarbonate (>27 mEq/L serves as screening biomarker). 2

Etiology-Specific Workup

For Suspected Intrinsic (Parenchymal) Disease

• Serologic testing for connective tissue disease: ANA, RF, anti-CCP, anti-Scl-70, anti-Jo-1, myositis panel, MPO-ANCA. 3
• Consider bronchoscopy with bronchoalveolar lavage and/or transbronchial biopsy when diagnosis remains uncertain after HRCT, particularly to exclude infection, malignancy, or specific ILD subtypes. 1
• Surgical lung biopsy may be necessary when multidisciplinary discussion cannot reach consensus diagnosis. 1

For Suspected Extrinsic Disease

• Echocardiography to evaluate for heart failure with preserved ejection fraction causing pulmonary congestion. 5
• Neuromuscular evaluation: Creatine kinase, electromyography, nerve conduction studies, genetic testing if hereditary neuromuscular disease suspected. 4
• Sleep study with transcutaneous CO2 monitoring for patients with neuromuscular disease or obesity to detect nocturnal hypoventilation even when daytime gas exchange is normal. 4

Multidisciplinary Team Evaluation

Integrate findings through multidisciplinary discussion involving pulmonology, radiology, and rheumatology (when CTD suspected) to synthesize HRCT patterns, PFT results, and clinical features for accurate diagnosis and severity assessment. 1

Monitoring and Follow-Up

• Serial spirometry and DLCO every 3-6 months to detect progression. 1
• Define progressive pulmonary fibrosis by presence of ≥2 of the following within 12 months: worsening respiratory symptoms, physiological decline (≥10% relative decline in FVC or ≥15% relative decline in DLCO), or radiological progression on chest CT. 1, 3
• Six-minute walk test with continuous oximetry to assess functional capacity and detect exercise-induced desaturation. 2, 3, 6

Common Pitfalls to Avoid

• Do not diagnose restriction based on spirometry alone—always confirm with lung volume measurement, as reduced FVC can occur in severe obstruction. 1
• Do not overlook connective tissue disease screening—many patients with CTD-ILD have minimal or no extrapulmonary manifestations at presentation. 1, 3
• Do not assume normal daytime gas exchange excludes significant disease in neuromuscular patients—nocturnal hypoventilation often precedes daytime hypercapnia. 4
• Do not delay antigen identification and avoidance in hypersensitivity pneumonitis—this is the primary treatment when causative antigen is identified. 3