How should I interpret pulmonary function tests and diffusing capacity for carbon monoxide (DLCO) step by step?

How to Interpret Pulmonary Function Tests and DLCO: Step-by-Step Algorithm

Follow a systematic five-step approach: (1) assess technical quality first, (2) compare results to appropriate reference values using the 5th percentile as the lower limit of normal, (3) identify the physiological pattern (obstruction, restriction, or mixed), (4) evaluate DLCO and severity, and (5) integrate clinical context to answer the specific question that prompted testing. 1

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Step 1: Assess Technical Quality Before Trusting Any Numbers

Review the raw flow-volume curves and technical parameters before accepting computer-generated interpretations—this is the single most frequent source of error in PFT interpretation. 1

Spirometry Quality Criteria

• Require ≥3 acceptable maneuvers with reproducibility ≤150 mL for both FEV₁ and FVC 1
• Ensure forced expiration lasts ≥6 seconds in adults 1
• Visually inspect the flow-volume curve for rounded peaks, abrupt terminations, or coughing artifacts that indicate submaximal effort 1
• Incomplete inspiratory or expiratory effort produces simultaneous reduction in FEV₁ and FVC with a normal FEV₁/FVC ratio—interpret this as suboptimal effort, not true disease 1

DLCO Quality Criteria

• Grade A (highest quality) requires: inspired volume >90% of vital capacity, breath-hold time 8–12 seconds, and sample collection time <4 seconds 2
• Report the average DLCO from at least two Grade A maneuvers that are repeatable within 2 mL/min/mmHg 2
• For suboptimal tests (Grades B-D), report the average of the two best maneuvers with a cautionary comment that acceptability criteria were not fully met 2
• Inadequate inspired volume (<80% of vital capacity) renders the test unacceptable 2

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Step 2: Compare to Appropriate Reference Values

Use the 5th percentile of the reference population as the lower limit of normal for all parameters—never use fixed cut-offs like "80% predicted" or FEV₁/FVC <0.70. 1

Critical Reference Value Requirements

• Measure height with a calibrated stadiometer at the time of testing; never rely on self-reported height 1
• Select reference equations that match the patient's age, sex, measured height, and ethnicity 1
• All spirometric parameters (FVC, FEV₁, FEV₁/FVC) must be derived from the same reference source to maintain internal consistency 1
• The fixed FEV₁/FVC <0.70 threshold generates false-positive COPD diagnoses in men >40 years and women >50 years, especially elderly never-smokers 1

Race/Ethnicity Adjustments (When Specific Equations Unavailable)

• Black patients: multiply FEV₁, FVC, and TLC by 0.88 1
• Asian-American patients: multiply by 0.94 1
• Do NOT apply these factors to FEV₁/FVC or FEV₁/VC ratios 1

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Step 3: Identify the Physiological Pattern

Start with the FEV₁/VC Ratio

The FEV₁/VC (or FEV₁/FVC) ratio is your first decision point—it determines whether obstruction is present. 3

Obstructive Pattern (FEV₁/VC <5th percentile)

• An FEV₁/VC ratio below the 5th percentile defines obstruction and predicts morbidity and mortality even when absolute FEV₁ is within normal limits 1
• Look for a concave shape on the flow-volume curve—this is the hallmark of airflow obstruction 3
• FEV₁ is proportionally more reduced than VC in obstructive patterns 3
• Measure total lung capacity (TLC) to assess hyperinflation: elevated TLC, residual volume (RV), or RV/TLC ratio supports emphysema, asthma, or other obstructive disorders 1

Clinical Pearl: In adult smokers with post-bronchodilator obstruction, a low DLCO greatly increases the probability of emphysema phenotype COPD, while normal DLCO makes chronic asthma more likely 4

Restrictive Pattern (Normal or High FEV₁/VC with Low VC)

• A normal or increased FEV₁/VC ratio (>85–90%) suggests a restrictive pattern 3
• Look for a convex pattern on the flow-volume curve 3
• Critical: Reduced VC alone does NOT prove restriction—only about 50% of cases with low VC have low TLC 1, 3
• You must measure TLC to confirm true restriction: TLC below the 5th percentile with normal FEV₁/VC ratio confirms restrictive physiology 1

Pitfall to Avoid: Single-breath alveolar volume (VA) from DLCO testing systematically underestimates TLC by up to ~3 L in severe obstruction, markedly increasing the risk of misclassifying restrictive disease 1

Mixed Pattern

• Both FEV₁/VC ratio and TLC fall below the 5th percentile 1
• When FEV₁/VC is low and VC is reduced but TLC has not been measured, state that VC reduction likely reflects hyperinflation and that a superimposed restrictive component cannot be excluded without TLC assessment 1

Normal FEV₁/VC with Reduced FEV₁ and FVC

• This pattern may indicate suboptimal effort, patchy peripheral airway obstruction, or inability to sustain expiration long enough 1
• Repeat spirometry after bronchodilator administration: a significant increase (≥12% and ≥200 mL) supports reversible airflow obstruction 1

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Step 4: Evaluate DLCO and Assess Severity

DLCO Measurement and Reporting Standards

Always measure DLCO alongside spirometry and lung volumes, reporting results as absolute values, z-scores, and percent predicted using GLI 2017 reference equations, adjusted for hemoglobin. 2

• Hemoglobin concentration must be measured and reported—anemia artificially lowers DLCO while polycythemia increases it 2
• Results must be corrected to standard barometric pressure, particularly important at altitude 2
• Report DLCO in mL/min/mmHg with lower limit of normal at z-score of -1.64 2

DLCO Interpretation by Pattern

DLCO and FEV₁ correlate poorly—reduction in DLCO can occur even with normal spirometry, and both should be assessed independently. 2

Reduced DLCO with Normal Lung Volumes

• Suggests early interstitial lung disease, pulmonary vascular disease (including pulmonary hypertension), early emphysema, or anemia 2
• In patients with dyspnea of unknown cause, this pattern increases likelihood of pulmonary vascular disease 4

Reduced DLCO with Restrictive Pattern (Low TLC)

• Indicates interstitial lung disease, with severity correlating with extent of fibrosis on high-resolution CT 2
• In patients with spirometric restriction, a low DLCO increases pre-test probability of ILD, while normal DLCO makes chest wall restriction more likely 4

Reduced DLCO with Obstructive Pattern

• In emphysema, both DLCO and KCO are equally decreased 5
• Low DLCO (<60%) is associated with higher mortality (25%) and pulmonary morbidity (40%) in patients undergoing lung resection 1

Severity Grading

For obstructive, restrictive, and mixed defects, severity is primarily based on FEV₁ % predicted: 1

• Mild: >70%
• Moderate: 60–69%
• Moderately severe: 50–59%
• Severe: 35–49%
• Very severe: <35%

For DLCO: Values <60% are associated with higher mortality and pulmonary morbidity 1

Prognostic Threshold: DLCO below 40% predicted, or a decline in DLCO of more than 4 units, is associated with increased morbidity and mortality 4

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Step 5: Check Bronchodilator Response and Integrate Clinical Context

Bronchodilator Response

• A significant response is defined as an increase in FEV₁ or FVC of >12% AND >200 mL in adults (>12% in children 5–18 years) 3, 6
• Asthma is typically reversible, whereas COPD is not 6
• Important caveat: Absence of a response does not rule out clinical benefit from bronchodilator therapy 3

Clinical Context Integration

Never interpret DLCO in isolation—always consider in context of spirometry, lung volumes, and clinical presentation. 2

• Record respiratory symptoms (cough, phlegm, wheezing, dyspnea), smoking status, and recent bronchodilator use 7, 3
• Consider chest radiograph appearance, most recent hemoglobin value, and any suspicion of neuromuscular disease or upper airway obstruction 7, 3
• If borderline results, additional testing may be necessary to establish diagnosis 1

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Critical Pitfalls to Avoid

• Relying on computer interpretations without reviewing test quality is the most frequent error 1
• Using FEV₁/VC ratio to determine severity of obstruction (instead of FEV₁ % predicted) is incorrect 1
• Failing to measure lung volumes when restrictive pattern is suspected based on spirometry alone 1
• Not adjusting DLCO for hemoglobin and carboxyhemoglobin, especially when monitoring for toxicity 1
• Interpreting multiple parameters simultaneously inflates false-positive rates: examining three parameters yields 10% abnormal results in healthy subjects, rising to 24% when fourteen parameters are examined 1
• Maintaining inconsistent interpretation strategies within a laboratory can create the illusion of disease progression when it's actually due to changes in analytical approach 1
• Not recognizing that upper airway obstruction may be life-threatening despite being classified as only mildly reduced by FEV₁ % predicted 1

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Special Considerations for DLCO

Inter-Laboratory Variability

• DLCO variability between laboratories is substantially greater than for spirometry, making reference equation selection critical 7
• Laboratory directors should verify chosen DLCO reference equations by testing a local cohort of healthy individuals 7

Adjustments Required

• Elevated carboxyhemoglobin (e.g., in smokers) artificially lowers DLCO values 7
• Altitude reduces measured diffusion capacity due to lower barometric pressure—apply appropriate altitude adjustments 7
• Adjust predicted DLCO and KCO for alveolar volume when VA is abnormal to avoid misleading results 8, 5

Follow-Up Strategy

• Repeat DLCO at yearly intervals for monitoring disease progression in chronic conditions like alpha-1 antitrypsin deficiency, connective tissue disease-associated ILD, and other progressive lung diseases 2
• Progressive pulmonary fibrosis requires documentation of ≥10% relative decline in FVC or ≥15% relative decline in DLCO within one year 2