Diagnostic Pulmonary Function Testing: Lung Volumes, Airway Resistance, and Gas Distribution Analysis

Overview of Advanced Pulmonary Function and Lung Volume Testing

• Advanced lung volume tests evaluate volumes and capacities that cannot be measured using simple spirometry, vital capacity maneuvers, or Maximum Voluntary Ventilation ($\text{MVV}$).
• Diagnostics obtained from lung volume testing are paired with Slow Vital Capacity ($\text{SVC}$) testing performed within the same session to make necessary volumetric calculations.
• Primary testing modalities include:
  • Open-Circuit Multiple-Breath Nitrogen ($\text{N}_2$) Washout.
  • Single-Breath Nitrogen ($\text{N}_2$) Washout (used briefly for assessing gas distribution).
  • Closed-Circuit Multiple-Breath Helium ($\text{He}$) Dilution.
  • Body Plethysmography (commonly referred to as the "body box").
• Secondary Gas Distribution Assessment:
  • Distribution of ventilation can be secondarily derived from the results of a multi-breath nitrogen washout or a helium dilution test, though these are not standalone certified gas distribution tests.
• Central Target Measurement:
  • The primary objective of these testing techniques is to measure Functional Residual Capacity ($\text{FRC}$).
• Alternative Diagnostic Modalities:
  • Chest X-Ray: Allows visual assessment of rib spacing and the position of the diaphragm relative to the ribs to form educated estimates regarding air trapping or hyperinflation.
  • Computed Tomography (CT) / Magnetic Resonance Imaging (MRI): Advanced radiological imaging techniques that quantify volumetric data but involve high financial costs, radiation exposure (CT), injectable contrast media, or strong magnetic fields (MRI).
  • Routine pulmonary breathing tests remain the preferred standard diagnostic option.

Indications for Lung Volume Measurements

• Differentiating between obstructive and restrictive lung diseases. Restrictive lung disease can be definitively identified when measured lung volumes and capacities are reduced below normal limits.
• Staging the severity of restrictive lung disease.
• Evaluating therapeutic responses to medical or surgical interventions (such as evaluating volume expansion following a lobectomy).
• Preoperative patient evaluation.
• Quantifying the exact degree of hyperinflation and air trapping.
• Measuring Specific Airway Conductance ($\text{sG}_{aw}$):
  • Conductance ($\text{G}_{aw}$) represents the ease with which gas flows through the airways.
  • The lowercase prefix "$\text{s}$" stands for specific, indicating conductance normalized to a specific lung volume.
  • Specific conductance evaluates how effectively the airways conduct airflow at a designated lung volume, specifically measured at the End-Expiratory Level (EEL) or the level of $\text{FRC}$.

Circuit Designs and Equipment Configurations

• Body Plethysmography ("Body Box"):
  • The only testing modality that requires placing the patient inside a sealed enclosure resembling a telephone booth.
  • If a laboratory lacks a body box, lung volume measurements can still be effectively performed using nitrogen washout or helium dilution techniques.
• Open-Circuit Systems:
  • A breathing circuit setup that allows the patient to inhale a fresh supply of gas with every breath.
  • Used in open-circuit multiple-breath nitrogen washout testing.
• Closed-Circuit Systems:
  • A rebreathing circuit setup where exhaled gas is recirculated through the system.
  • Water Absorber (Desiccant): Required in testing circuits to eliminate condensation buildup in tubing, which would otherwise increase circuit resistance.
  • Carbon Dioxide ($\text{CO}_2$) Scrubber: Contains chemical absorbers (such as soda lime) to continuously remove exhaled $\text{CO}_2$ from the circuit, preventing rebreathing of $\text{CO}_2$ and maintaining normocapnic / eucapnic conditions ($\text{eucapnia}$).
  • Supplemental Oxygen ($\text{O}_2$): Added continuously into closed rebreathing circuits to replace oxygen consumed by the patient, maintaining normoxic conditions and constant circuit gas volume.

Lung Volumes, Capacities, and Diagnostic Ratios

• Functional Residual Capacity ($\text{FRC}$):
  • Directly measured during volume testing.
  • Defined as the volume of gas remaining in the chest at the end of a quiet, normal exhalation (End-Expiratory Level, or EEL).
• Residual Volume ($\text{RV}$):
  • A calculated parameter obtained by subtracting Expiratory Reserve Volume ($\text{ERV}$) measured during Slow Vital Capacity ($\text{SVC}$) testing from the measured $\text{FRC}$:     $\text{RV} = \text{FRC} - \text{ERV}$
• Total Lung Capacity ($\text{TLC}$):
  • A calculated parameter obtained by adding the measured $\text{FRC}$ to the Inspiratory Capacity ($\text{IC}$) measured during $\text{SVC}$ testing:     $\text{TLC} = \text{FRC} + \text{IC}$
• Residual Volume to Total Lung Capacity Ratio ($\text{RV}/\text{TLC}$):
  • Represents the fraction or percentage of total lung volume that cannot be exhaled.
  • Elevated $\text{RV}/\text{TLC}$ ratios indicate air trapping and hyperinflation.
• Thoracic Gas Volume ($\text{V}_{TG}$):
  • Defined as the absolute volume of gas present in the chest at a specific point in time.
  • Obtained exclusively via Body Plethysmography.
  • When measured at the End-Expiratory Level (EEL), $\text{V}_{TG}$ is equivalent to $\text{FRC}$ ($\text{V}_{TG} = \text{FRC}$).

Pathophysiology of Airway Resistance and Compliance

• Obstructive Pathophysiology:
  • Air trapping causes volume and pressure buildup inside the chest cavity.
  • Patients are forced to breathe at higher lung volumes ("breathing on top of trapped air"), operating on a less compliant portion of the pressure-volume curve.
  • Overcoming built-up intra-thoracic pressure increases airway resistance and the total work of breathing.
• Restrictive Pathophysiology:
  • Lungs become pathologically stiff with high elastic recoil forces ("rubber band lungs").
  • Patients breathe at lower lung volumes and must overcome excessive elastic resistance to inhale gas.
  • Compliance is reduced, significantly increasing work of breathing during inspiration.
• Clinical Objective:
  • Restoring a patient's $\text{FRC}$ toward normal levels restores optimal lung compliance and reduces excessive work of breathing.

Open-Circuit Multiple-Breath Nitrogen ($\text{N}_2$) Washout Test

• Test Principle:
  • Baseline gas in human lungs contains approximately $78\%$ nitrogen ($75\%\text{--}80\%$) in equilibrium with ambient room air.
  • The patient breathes $100\%$ oxygen ($\text{O}_2$) to clear or "wash out" nitrogen residing in the lungs.
• Circuit Equipment:
  • Open-circuit setup connected to a $100\%$ $\text{O}_2$ supply.
  • Expiratory flow spirometer.
  • Nitrogen Analyzer: Uses Emission Spectroscopy (or rapid gas chromatography) connected via a sampling line at the patient's mouth.
• Testing Protocol:
  • Patient applies nose clips and forms a tight mouth seal around the mouthpiece.
  • Patient breathes quiet tidal breaths on room air to establish a stable End-Expiratory Level (EEL).
  • Software switches the inhalation valve to $100\%$ $\text{O}_2$ at the start of an inhalation at EEL.
  • Patient continues relaxed, normal tidal breathing while inhaling $100\%$ $\text{O}_2$ continuously.
  • Exhaled $\text{N}_2$ concentration is monitored on a washout tracing graph plotting volume versus $\text{N}_2$ concentration.
  • Test ends when exhaled $\text{N}_2$ concentration drops continuously down to $1.5\%$.
• Acceptability and Quality Control Criteria:
  • Trial Requirement: Only 1 technically acceptable trial is required.
  • Rest Interval: If repeated, a 15-minute rest period is required between trials to allow lung $\text{N}_2$ concentration to return to normal baseline conditions.
  • Reproducibility: If multiple acceptable trials are performed, measured $\text{FRC}$ values must agree within $10\%$ of each other. The reported $\text{FRC}$ is the average of acceptable trials.
  • Washout Duration:
  • Healthy subjects wash out nitrogen in approximately 3 minutes.
  • Obstructive disease prolongs washout time proportional to severity ($> 7\,\text{minutes}$ indicates severe obstruction or air trapping).
  • Circuit Leaks:
  • Graph must show a continuously falling $\text{N}_2$ curve down to $1.5\%$.
  • Spikes or sudden increases in $\text{N}_2$ concentration ($> 1\%$ increase) indicate a system leak or patient error (e.g., breaking the mouth seal or inhaling room air).
  • If a leak occurs, the trial must be aborted, followed by a 15-minute rest period before retesting.

Closed-Circuit Multiple-Breath Helium ($\text{He}$) Dilution Test

• Test Principle:
  • Patient rebreathes a known volume of gas containing $10\%$ helium ($\text{He}$) in a closed spirometer system.
  • Helium is an inert gas not naturally present in the lungs. Gas redistributes down its concentration gradient until equilibrium is established between the system box and the lungs.
• Circuit Equipment:
  • Closed rebreathing circuit.
  • Helium Analyzer: Uses a Thermal Conductivity Analyzer (or gas chromatography).
  • $\text{CO}_2$ absorber (soda lime) to remove exhaled carbon dioxide.
  • Supplemental $\text{O}_2$ line adding continuous oxygen to replace consumed oxygen.
  • Water absorber to prevent condensation buildup.
• Testing Protocol:
  • Equipment is prepared, and patient seal is verified with nose clip and mouthpiece.
  • Patient breathes room air normally to establish a stable EEL baseline.
  • Switch-in: At EEL, the valve opens to connect the patient to the closed circuit containing $10\%$ $\text{He}$.
  • Patient continues normal tidal rebreathing.
  • Helium concentration is monitored as it falls to a stable plateau.
• End-of-Test Criteria:
  • Equilibrium is achieved when $\text{He}$ concentration changes by no more than $0.02\%$ over a 30-second period.
  • OR when the maximum test time limit of 10 minutes is reached.
• Acceptability and Quality Control Criteria:
  • Trial Requirement: Only 1 technically acceptable trial is required.
  • Rest Interval: If repeated, a 5-minute rest period is required (helium clears rapidly into ambient air).
  • Reproducibility: Multiple acceptable trials must have $\text{FRC}$ values agreeing within $10\%$ of each other. The average $\text{FRC}$ is reported.
  • Equilibration Time:
  • Healthy lungs equilibrate in approximately 3 minutes.
  • Prolonged equilibration time up to $10\,\text{minutes}$ indicates obstruction.
  • Switch-In Error:
  • A correction factor accounting for deviations from the exact EEL during switch-in.
  • A large switch-in error requires stopping and repeating the test.
  • Sample baseline output parameters may show an $\text{FRC}$ value of $3.81\,\text{L}$ with an equilibration time of $4.5\,\text{minutes}$.

Diagnostic Limitations of Gas Dilution and Washout Methods

• Reliance on Well-Ventilated Lung Units:
  • Both $\text{N}_2$ washout and $\text{He}$ dilution rely on all lung regions being well-ventilated and accessible to circuit gas distribution.
• Underestimation in Obstructive Lung Disease:
  • In patients with severe obstructive lung disease (e.g., COPD) or significant gas trapping, poorly ventilated lung units or bullae do not participate efficiently in gas dilution or washout within standard timeframes.
  • As a result, $\text{FRC}$, $\text{RV}$, and $\text{TLC}$ values derived from gas dilution/washout tests can be significantly underestimated.
• Clinical Interpretations:
  • Body Plethysmography evaluates total thoracic gas volume regardless of ventilation status, avoiding volume underestimation.
  • When using gas dilution/washout systems, extending test duration ($> 7\,\text{minutes}$ for washout, $10\,\text{minutes}$ for helium dilution) allows clinicians to infer the presence and severity of poorly ventilated lung regions and gas distribution abnormalities.

Questions & Discussion

• Question: What does "jaw" stand for in $s_{jaw}$?
  • Answer: Conductance ($\text{G}_{aw}$). The lowercase "$s$" stands for specific, representing specific airway conductance ($\text{sG}_{aw}$), typically measured at the end-expiratory level ($\text{FRC}$).
• Question: What is the rule regarding FRC agreement across multiple trials?
  • Answer: Only one technically acceptable trial is required. However, if institutional policy or physician preference requires multiple trials, the calculated $\text{FRC}$ values from acceptable trials must agree within $10\%$ of one another. The final reported $\text{FRC}$ value is the average of those trials.