Pulmonary function testing

Pulmonary function tests (PFTs) measure lung volumes and other metrics of pulmonary function. They can be used to diagnose ventilatory disorders and differentiate between obstructive and restrictive lung diseases. The most common PFT is spirometry, which requires the patient to breathe forcefully through their mouth into an external device. This simple and cost-effective test measures both dynamic and static lung volume (with the exception of residual volume and total lung capacity) and airflow rates. Full-body plethysmography measures both residual volume and total lung capacity in a sealed chamber. Single-breath diffusing capacity helps determine if the alveolar membrane is thickened (e.g., in pulmonary fibrosis) or destroyed (e.g., in emphysema), and if the pulmonary vasculature is affected (e.g., in pulmonary hypertension).

The most common indications and contraindications for pulmonary function testing are listed below.

• Indications ^[1]
  • Unexplained respiratory signs and/or symptoms
  • Lung disease: to monitor progression and treatment response
  • Preoperative risk assessment in selected cases (e.g., CPET prior to lung reduction surgery)
  • Disability evaluation (e.g., for insurance or legal purposes)
• Relative contraindications ^[1]
  • Acute MI, decompensated heart failure, unstable pulmonary embolism, pneumothorax
  • Recent surgery: brain, eye, sinus, thorax, or abdomen
  • Cerebral aneurysm
  • Respiratory infections
  • Hemoptysis

General principles ^[2][3]

• The first step in PFT interpretation is confirming the validity of the measurements.
• Spirometry and body plethysmography measure lung volumes and can differentiate between obstructive vs. restrictive lung diseases.
• Additional testing may be indicated to further characterize the disease and narrow down the differential diagnosis, e.g.:
  • Single-breath diffusing capacity
  • Bronchial challenge testing or bronchodilator responsiveness testing
  • Respiratory muscle function testing
• A diagnosis cannot be made based on PFT results alone.

Correlate PFT results with a detailed history and findings from a comprehensive physical examination and additional diagnostic studies.

Normal lung volumes

Normal lung volumes depend on age, height, and sex. The values listed below are for a healthy young adult. ^[1][2][3]

Altered PFTs ^[2][3]

Approach

• Assess lung volumes (on spirometry and/or body plethysmography): to determine the main pattern of disease
  • ↓ FEV₁/FVC ratio
    • Normal or ↑ TLC: obstructive lung disease
    • ↓ TLC: mixed obstructive and restrictive lung disease (e.g., COPD plus obesity, or silicosis)
  • ↓ FVC and ↓ TLC: restrictive lung disease
• Assess lung diffusion capacity (by measuring DL_CO)
  • To further characterize obstructive and restrictive lung diseases
  • Abnormal DL_CO in patients with normal lung volumes suggests one of the following:
    • Pulmonary vascular diseases (e.g., pulmonary hypertension)
    • Other systemic disorders (e.g., anemia)
    • Early interstitial lung disease
  • See “Interpretation of DL_CO.”
• Determine disease severity:
  • Using either z-scores or fixed values; see “Severity assessment.”
  • See also “Classification of asthma severity” and “COPD classification.”
• Consider specialized testing in obstructive lung disease.
  • Bronchodilator responsiveness test to assess the reversibility of the obstruction
  • Bronchoprovocation test to assess airway hyperresponsiveness
• Correlate results: with clinical, laboratory, and imaging findings; see “Differential diagnoses”

Severity assessment ^[7][8]

For patients with obstructive or restrictive lung diseases, disease severity may be assessed using either:

• Z-scores
  • Based on LLN (i.e., 5th percentile) and ULN (i.e., 95th percentile) across different age groups
  • Higher diagnostic accuracy than fixed values
• Fixed values
  • Based on average values in healthy middle-aged men (e.g., FEV₁ > 80% of predicted) ^[7]
  • May lead to inaccurate results ^[8]

The American Thoracic Society and European Respiratory Society recommend the use of z-scores to assess disease severity. However, despite their limitations, fixed values are still recommended by the Global Initiative for Chronic Obstructive Lung Disease. ^[7][8]

Differential diagnoses ^[5]

Obstructive lung disease

• Definition: increased resistance to airflow caused by narrowing of airways
• Etiology
  • COPD (chronic bronchitis, emphysema)
  • Bronchial asthma
  • Bronchiectasis, cystic fibrosis
  • Narrowing of extrathoracic airways: laryngeal tumors, vocal cord palsy
• Diagnostic findings
  • Imaging findings
    • Hyperlucency of lung tissue
    • Horizontal ribs and widened intercostal spaces
    • Increased anteroposterior diameter
    • Diaphragm pushed down and flattened
  • A-a gradient: ↑

Restrictive lung disease

• Definition: impaired ability of the lungs to expand (as a result of reduced lung compliance)
• Intrinsic causes (parenchymal diseases)
  • Interstitial lung disease
    • Sarcoidosis
    • Pneumoconioses
    • ARDS
    • Idiopathic pulmonary fibrosis
    • Hypersensitivity pneumonitis
    • Granulomatosis with polyangiitis
    • Pulmonary Langerhans cell histiocytosis
    • Radiation-induced lung injury
    • Drug-induced interstitial lung disease (e.g., due to MTX, bleomycin, busulfan, amiodarone)
  • Alveolar (e.g., pneumonia, pulmonary edema, hemorrhage)
• Extrinsic causes (i.e., extrapulmonary conditions that change the mechanics of respiration)
  • Diseases of the pleura and pleural cavity (e.g., chronic pleural effusion, pleural adhesions, pneumothorax)
  • Deformities of the thorax/mechanical limitation; (e.g., kyphoscoliosis; , ankylosing spondylitis, obesity, ascites, pregnancy)
  • Respiratory muscle weakness; (e.g., phrenic nerve palsy, myasthenia gravis, polio, GBS, ALS, myopathies): See “Respiratory muscle function.” ^[9]
• Diagnostic findings
  • Imaging findings: depends on the underlying disease (can be normal)
    • Interstitial lung disease: reticular opacities (sign of fibrosis)
    • Pleural effusion: unilateral blunting of the costophrenic angle
    • Pneumothorax: unilateral pleural line with reduced/absent lung markings
  • A-a gradient
    • Normal (extrinsic causes)
    • ↑ (intrinsic causes)

Other

• Pulmonary vascular diseases
  • Pulmonary hypertension
  • Pulmonary embolism
  • Hepatopulmonary syndrome
• Systemic disorders
  • Carboxyhemoglobinemia (e.g., due to smoking)
  • Anemia
  • Polycythemia
  • Mild heart failure and left-to-right cardiac shunts
• Diagnostic findings
  • Imaging findings: depend on the underlying disease (can be normal)
  • Normal lung volumes on spirometry and plethysmography
  • Abnormal DL_CO findings; see also “Interpretation of DL_CO.”

Indications

Spirometry is the best initial test for the evaluation of pulmonary function; see “Indications” above.

Procedure ^[5]

• The patient breathes forcefully through their mouth into an external device.
• Four phases of inspiration and expiration are measured to determine lung volumes and airflow rates. ^[1]
  • Maximal inspiration: measures vital capacity (VC)
  • Forced rapid expiration: measures forced expiratory volume in 1 second (FEV₁)
  • Continued complete expiration for up to 15 seconds: measures expiratory vital capacity (EVC) and forced vital capacity (FVC)
  • Repeat maximal inspiration: measures inspiratory vital capacity (IVC)
• Flow-volume loops (i.e., graphical representation of spirometry results) are generated to demonstrate inspiratory and expiratory airflow (y-axis) against lung volume (x-axis)
• Can be combined with exercise to assess cardiopulmonary performance and metabolism (i.e., CPET)

Parameters

IVC, EVC, and FVC values are similar in young healthy individuals. However, IVC > EVC > FVC in patients with obstructive lung disease. ^[12][13]

Interpretation

See “PFT findings in obstructive vs. restrictive lung diseases.”

Specialized tests (i.e., bronchial challenge tests and/or bronchodilator responsiveness testing) may help distinguish bronchial asthma from other causes of obstructive lung disease.

Medications that reverse bronchospasm (e.g., epinephrine, atropine) should be kept at hand during the methacholine challenge test because the test may trigger a life-threatening asthma attack!

In an indirect bronchial challenge test, bronchoconstriction may be induced by exercise, hyperventilation, or mannitol. ^[16]

Plethysmography is the gold standard test for measuring lung volumes and, unlike spirometry, it can also measure TLC and RV.

Indications ^[17]

• Patients who cannot actively participate in spirometry
• Obstructive lung disease on spirometry: to evaluate for air trapping (e.g., in emphysema)
• Restrictive lung disease: to distinguish between extrinsic vs. intrinsic causes

Measurements in plethysmography are independent of active patient participation.

Procedure ^[17]

• Lung volumes are measured in a sealed chamber
• The air pressure in the cabin is inversely proportional to the air pressure in the lungs.

Parameters ^[17]

Includes spirometry parameters, plus:

• Airway resistance (R_aw): the resistance to airflow from the mouth to the alveoli during inspiration and expiration
• Residual volume (RV)
• Total lung capacity (TLC)
• Thoracic gas volume (TGV or VGT): intrathoracic air volume after normal expiration
• Lung compliance (measured using an esophageal probe)

Nonmobilizable lung volumes can be measured.

Interpretation

See “PFT findings in obstructive vs. restrictive lung diseases.”

Single-breath diffusing capacity measures the ability of the alveoli to transfer gases to the pulmonary capillaries.

Indications ^[4][18]

• Restrictive lung disease to differentiate between:
  • Intrapulmonary (e.g., interstitial lung disease) causes
  • Extrapulmonary (e.g., pleural effusion, respiratory muscle weakness) causes
• Intraparenchymal lung disease: to monitor disease progression
• Hypoxemia that remains unexplained after spirometry (e.g., due to pulmonary embolism)

Procedure ^[18]

• The patient inhales an inert gas (e.g., helium) and a low concentration of carbon monoxide (CO).
• The patient then holds their breath for ∼ 10 seconds.
• On exhalation, the concentration of CO in the breath is measured.

Parameters ^[18]

Results are highly dependent on hemoglobin concentration; reference values are therefore routinely adjusted.

• Carbon monoxide transfer coefficient (K_CO): the amount of CO per unit time per unit partial pressure that is transferred from the alveolus to the pulmonary capillary
• Diffusing capacity of the lung for carbon monoxide (DL_CO) : the product of K_CO and total alveolar volume (V_A)

Certain activities, body positions, and physiologic states (e.g., exercise, supine position, pregnancy, obesity) can increase pulmonary blood volume thereby increasing DL_CO.

Interpretation

Indication ^[4][24]

Consider for restrictive lung disease to diagnose and monitor patients with respiratory muscle weakness.

Procedure ^[24]

Test of inspiratory (e.g., diaphragm, external intercostal muscles) and expiratory (e.g., abdominal muscles, internal intercostal muscles) muscle function

• The patient inhales and exhales with as much force as possible against a closed mouthpiece or a pressure transducer in one nostril.
• The pressure generated at the mouth or nostril is recorded.

Parameters ^[24]

• Maximal inspiratory pressure (MIP)
  • Measure (in cmH₂O) to evaluate inspiratory muscle function
  • Determined by having the patient inhale with as much force as possible against a closed mouthpiece
  • Values below -80 cmH₂O in men and below -70 cmH₂O in women rule out significant inspiratory muscle weakness.
• Sniff nasal inspiratory pressure (SNIP)
  • Measure (in cmH₂O) to evaluate inspiratory muscle function
  • Determined by having the patient inhale with as much force as possible against a pressure transducer in one nostril .
  • Values below -70 cmH₂O in men and below -60 cmH₂O in women rule out significant inspiratory muscle weakness.
• Maximal expiratory pressure (MEP)
  • Measure (in cmH₂O) to evaluate expiratory muscle function
  • Determined by having the patient exhale with as much force as possible against a closed mouthpiece
  • Values above 130 cmH₂O in men and above 100 cmH₂O in women rule out significant expiratory muscle weakness.

Interpretation ^[24]

Alterations may be seen in:

• Depression of the respiratory center due to:
  • Severe metabolic encephalopathy
  • Opioid overdose
  • Brainstem stroke
  • Traumatic brain injury
• Phrenic nerve palsy due to:
  • Anterior horn cell disorder (e.g., amyotrophic lateral sclerosis)
  • Peripheral neuropathy (e.g., Guillain-Barré syndrome)
• Myasthenia gravis
• Myopathies; (e.g., thyrotoxic myopathy, muscular dystrophy)