A discussion of reference values, uses of PFTs, and study comparisons wrap up this two-part article.

To interpret the results of PFTs, reference values are required.¹ While the ideal reference values reflect the patient population served by a PF laboratory, these are difficult to obtain. Most PF laboratories use equations derived from studies of healthy populations to generate predicted values specific for a patient’s gender, height, age, and ethnicity. Results are then reported both as raw numbers and as percentages of the reference values.

Several sets of equations are currently in use. For pediatric patients, the most common standards were published by Hsu et al.² This group studied 1,805 healthy white, Hispanic, and black children and young adults. For adult patients, the most widely used reference values and equations were published by Crapo et al.³ Recently, reference values and equations derived from the Third National Health and Nutrition Examination Survey⁴ were published. The authors studied 7,249 never-smoking white, black, and Hispanic children and adults ranging in age from 8 to 80 years. This data set is the most comprehensive published and has the advantage of providing a single set of equations for both children and adults within each of three ethnic categories and specific to each gender.

Clinical Uses of PFTs
PFTs are useful in the diagnosis of diseases that cause airway obstruction, chest restriction, or both. Airway obstruction is identified as a lowered ratio of FEV₁ to FVC due to a reduction in FEV₁. The flow rate in the airways during exhalation is slowed. In severe airway obstruction, some parts of the lung may never empty, causing a rise in ERV and FRC. This may result in a drop in FVC, which limits the reduction in FEV₁:FVC and underestimates the severity of airway obstruction.

Chest restriction is an inability to reach a normal total lung capacity upon inspiration. This may be due to chest-wall or lung stiffness, skeletal deformity (such as kyphoscoliosis), or respiratory muscle weakness due to intrinsic muscle disease or abnormal innervation. Total lung capacity is more sensitive and accurate for detecting chest restriction, but FVC is easier to obtain technically and easier to perform for patients. FVC is reduced with chest restriction, but the FEV₁:FVC is preserved. In the interpretation of PFTs, however, the total lung capacity measurement defines chest restriction, while the FVC suggests chest restriction.

Common causes of airway obstruction include asthma and COPD. In these diseases, PFTs may be useful in diagnosis and/or management. In asthma, reversible airway obstruction is a key feature of disease. PFTs demonstrating airway obstruction that improves or worsens with time or improves in response to bronchodilators help confirm the diagnosis. PFTs can help to identify exacerbations of disease and identify successful treatments.

In COPD, much of the airway obstruction is irreversible, but there may also be a reversible component that may respond to bronchodilator treatment. PFTs can help identify these patients. Over time, PFTs may help track worsening severity of airway obstruction.

In the acute care setting, for acute exacerbations of asthma and sometimes COPD, bedside spirometric testing of FEV₁ may be useful to demonstrate the effect of acute bronchodilator treatments and to track improvement over hours after the administration of systemic steroid therapy. Used in this way, PFTs may help clinicians decide whether to admit or discharge patients.

Diseases characterized by chest restriction include idiopathic pulmonary fibrosis, paralysis of either or both hemidiaphragms, myasthenia gravis, and kyphoscoliosis. In addition, certain medications, such as amiodarone and cancer chemotherapeutic agents, can cause fibrosis of the lung and subsequent chest restriction due to lung stiffness. PFTs can be useful in providing adjunctive information for these diseases by measuring the severity of chest restriction. Over time, PFTs may help reveal disease progression by showing gradual worsening of chest restriction, as in the cases of idiopathic pulmonary fibrosis and scoliosis. Chest restriction may wax and wane in diseases such as myasthenia gravis, which are characterized by exacerbations; repeated measurements of FVC may help to track day-to-day changes. For patients with an FVC that is dropping below 800-1,000 mL, the measurement may help guide the timing for the initiation of ventilatory support. Conversely, for ventilated patients with an FVC that rises past 800-1,000 mL, the measurement may facilitate a decision to extubate. Under these circumstances, laboratory testing methods are often impractical and measurements are made using less accurate bedside methods or through ventilator circuits.

Comparing Studies Over Time
Many clinicians use serial PFTs to track the progression of various diseases. For example, spirometric values in patients with cystic fibrosis tend to decrease over time. The average drop is approximately 2% per year, but varies markedly from patient to patient. The percent of predicted FEV1 in these patients is directly linked to 5-year predicted survival, and a dropping measurement suggests a worsening prognosis.⁵

Using serial PFTs, however, can raise new problems with interpretation. American Thoracic Socity criteria⁶ suggest that a 10% change in FEV₁ or FVC is significant. That interpretation may be compromised, however, if the serial values are obtained using different machines, even within a single laboratory (and especially if the values are obtained by different laboratories). While most laboratories now adhere to ATS standards, small variations in technique and small differences in the measurement ability of different machines may result in significant machine-to-machine or center-to-center differences when no physiological differences truly exist.³ To minimize these differences due to procedure and technique, rigid adherence to ATS guidelines⁶ is recommended. When practical, identical machines and procedures should be used for each patient for whom serial PFTs are performed.

Summary
PFTs are commonly used to diagnose airway obstruction and chest restriction. PFTs are useful for the diagnosis of a variety of diseases that compromise the normal physiology of breathing. PFTs are also useful in detecting changes in disease over time that require treatment or are a result of treatment. The usefulness of PFTs depends on the reproducibility and accuracy of measurements. Reproducible, accurate measurements rely on good quality control and adherence to standard procedures. When properly obtained, serial measurements of PFTs can help guide the management of various diseases.

Theodore G. Liou, MD, is assistant professor, and Richard E. Kanner, MD, is professor, division of respiratory, critical care, and occupational pulmonary medicine, Department of Internal Medicine, University of Utah, Salt Lake City

References
1. Crapo RO. The role of reference values in interpreting lung function tests. Eur Respir J. 2004;24(3):341-2.
2. Hsu KHK, Jenkins DE, Hsi BP, et al. Ventilatory functions of normal children and young adults—Mexican-American, white and black. I. Spirometry. J Pediatr. 1979;95(2):14-23.
3. Crapo RO, Morris AH, Gardner RM. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis. 1981;123(6):659-64.
4. Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general US population. Am J Respir Crit Care Med. 1999;159(1):179-87.
5. Liou TG, Adler FR, Fitzsimmons SC, et al. Predictive five year survivorship model of cystic fibrosis. Am J Epidemiol. 200;153(4):345-52.
6. Standardization of Spirometry 1994 Update. American Thoracic Society. Am J Respir Crit Care Med. 1995:152(3):1107-36.