Can pulmonary fibrosis present with a decreased Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) without a restrictive pattern on Pulmonary Function Tests (PFTs), as seen in a patient with a DLCO of 79%?

Can Pulmonary Fibrosis Present with Isolated DLCO Reduction Without Restrictive Pattern?

Yes, pulmonary fibrosis can absolutely present with decreased DLCO (79% in this case) without a restrictive pattern on PFTs, and this represents a clinically significant finding that should not be dismissed. 1, 2, 3

Early Disease Presentation

• DLCO reduction is the earliest and most sensitive PFT abnormality in interstitial lung disease (ILD) and pulmonary fibrosis, frequently preceding changes in lung volumes. 1
• Approximately 25% of patients with idiopathic pulmonary fibrosis (IPF) have normal total lung capacity (TLC) at initial evaluation, and more than half have normal forced vital capacity (FVC). 3
• In one study of newly diagnosed IPF patients, 27% had no restrictive pattern (normal TLC) despite having IPF confirmed by clinical and radiographic criteria. 3

Clinical Significance of DLCO 79%

• A DLCO of 79% represents mild reduction (normal is ≥80% predicted) and warrants further investigation for underlying ILD. 1
• Even patients with preserved FVC (≥80%) but moderate-to-severe DLCO decrease (<60%) at diagnosis show increased risk of progression, death, or lung transplantation. 2
• In IPF patients with preserved FVC, 58.7% had DLCO <60%, and most of these patients (61.4%) demonstrated functional progression with higher 3-year mortality (20.45%). 2

Diagnostic Approach

When DLCO is reduced but spirometry and lung volumes are normal or near-normal, the following algorithm should guide evaluation: 1, 4

• Obtain high-resolution CT (HRCT) chest as the primary imaging modality to evaluate for interstitial lung disease patterns, particularly usual interstitial pneumonia (UIP) pattern with honeycombing, ground-glass opacities, or reticulation. 1, 4
• If HRCT shows definite UIP pattern with honeycombing, this is sufficient to establish IPF diagnosis in the appropriate clinical context (after excluding other causes of ILD). 4
• If HRCT findings are indeterminate or show possible UIP pattern, video-assisted surgical lung biopsy should be considered through multidisciplinary discussion. 4

Pathophysiologic Mechanisms

• The isolated DLCO reduction reflects early gas-exchange impairment from ventilation-perfusion (V/Q) mismatching and oxygen diffusion limitation across thickened alveolar-capillary membranes, which occurs before significant volume loss develops. 5
• In IPF, DLCO corrected for alveolar volume (KCO) correlates with mechanisms of hypoxemia during exercise, including V/Q mismatching and O2 diffusion limitation. 5
• Pulmonary vascular abnormalities modulate gas exchange in IPF, particularly during exercise, even when resting lung volumes remain preserved. 5

Prognostic Implications

• Serial monitoring every 3-6 months for at least 1 year is required to establish disease trajectory and determine treatment necessity. 1
• A decline in DLCO ≥10% predicted over 1 year is independently associated with 2.3-fold increased risk of subsequent mortality, regardless of FVC changes. 6, 7
• Even smaller declines (≥2% or ≥5% predicted) in DLCO inform prognosis and are associated with increased mortality risk. 7

Critical Pitfalls to Avoid

• Do not dismiss reduced DLCO simply because spirometry and lung volumes are normal—this represents early disease that requires investigation. 1, 2
• Do not assume preserved FVC (>80%) indicates "early" or "mild" disease if DLCO is significantly reduced (<60%), as these patients have worse outcomes. 2
• Do not rely on spirometry alone to rule out restrictive disease; TLC measurement by body plethysmography is required to definitively exclude restriction. 4
• Ensure DLCO measurements are adjusted for hemoglobin and carboxyhemoglobin levels for accurate interpretation. 1, 8

Additional Evaluation

• Perform 6-minute walk test with continuous pulse oximetry to assess for exertional desaturation, which may be present even with normal resting PFTs. 4
• Obtain resting arterial blood gas to evaluate for hypoxemia or increased alveolar-arterial oxygen gradient. 4
• Search for clinical and laboratory signs suggesting specific ILD etiologies (connective tissue disease, hypersensitivity pneumonitis, drug-induced ILD) before diagnosing IPF. 4