What Pulmonary Function Test (PFT) parameters are most affected as Interstitial Lung Disease (ILD) advances?

PFT Parameters Most Affected in Progressive Interstitial Lung Disease

Diffusing capacity for carbon monoxide (DLCO) is the most significantly affected pulmonary function test parameter as interstitial lung disease advances, followed by forced vital capacity (FVC). 1

Primary PFT Changes in Progressive ILD

Most Affected Parameters (In Order of Sensitivity)

1. DLCO (Diffusing Capacity)

   • First parameter to become abnormal in early ILD 2, 3
   • Shows most significant decline as disease progresses 1
   • Correlates strongly with disease extent on HRCT 1
   • Highly predictive of long-term outcomes, especially over 2-year periods 1
   • Decline of ≥15% indicates significant disease progression 4

2. FVC (Forced Vital Capacity)

   • Second most affected parameter 1
   • Decline of ≥5-10% indicates clinically significant progression 1, 4
   • Widely used as primary endpoint in clinical trials 5
   • More specific but less sensitive than DLCO for disease progression 4

3. TLC (Total Lung Capacity)

   • Becomes reduced as restrictive pattern develops 1, 5
   • Shows respectable validity as a marker for disease extent 5

Early Subtle Changes

• Increased FEV1/FVC ratio - may be the earliest spirometric abnormality in patients with normal FVC, TLC, and DLCO 3
• Increased expiratory flows (FEF25, FEF25-75, FEF75) - can identify early ILD before traditional parameters become abnormal 3

Pathophysiological Mechanisms

1. Gas Exchange Impairment

   • Impressive arterial desaturation during exercise 1
   • Abnormal increases in alveolar-arterial oxygen gradient (P(a-a)O2) 1
   • Multiple mechanisms contribute:
     • Ventilation/perfusion (V̇/Q̇) mismatching
     • Oxygen diffusion limitation
     • Low mixed venous PO2
     • Possible right-to-left intracardiac shunting 1

2. Ventilatory Abnormalities

   • Increased ventilatory demand due to:
     • Increased dead space ventilation (Vd/Vt)
     • Inefficient ventilation (V̇e/V̇CO2)
     • Hypoxemia
     • Early onset metabolic acidosis
     • Pulmonary hypertension
     • Increased central drive 1
   • Abnormal breathing pattern with increased respiratory frequency and reduced tidal volume 1

Monitoring Recommendations

1. Regular PFT Assessment

   • Perform baseline PFTs (spirometry and DLCO) in all patients with suspected ILD 1, 2
   • High-risk patients (e.g., systemic sclerosis): PFTs every 6 months 1
   • Moderate-risk patients: Annual PFTs 1, 2
   • Consider more frequent monitoring in first 3-4 years of disease 1

2. Criteria for Disease Progression

   • Relative decline in FVC ≥10% 4
   • Relative decline in DLCO ≥15% 4
   • Combination of worsening respiratory symptoms, absolute decline in FVC ≥5% or DLCO ≥15%, and radiological progression 4

Clinical Pearls and Pitfalls

• Pearl: DLCO <70% predicts higher likelihood of exercise desaturation 1
• Pitfall: Relying solely on FVC may miss early disease - include DLCO in assessment 5
• Pearl: High FEV1/FVC ratio may allow identification of ILD in earliest stages with simple spirometry 3
• Pitfall: PFTs can be normal in early ILD despite radiographic changes - HRCT is more sensitive for early detection 2
• Pearl: Combined physiologic assessment (FVC + DLCO) provides better prognostic information than either measure alone 4

Conclusion

While FVC has become the most commonly used parameter in clinical trials, the evidence suggests DLCO is more sensitive for detecting early disease and monitoring progression. A comprehensive approach using both parameters provides the most complete assessment of ILD progression and prognosis.