Lactology Foundation

Pulmonary Function Testing

They are used to establish baseline lung function, evaluate dyspnea, detect pulmonary disease, monitor effects of therapies used to treat respiratory disease, evaluate respiratory impairment or disability, evaluate operative risk, and perform surveillance for occupational-related lung disease. It may also be used in research and clinical trials and epidemiological surveys.

Spirometry
Description
Spirometry assesses the integrated mechanical function of the lung, chest wall, respiratory muscles, and airways by measuring the total volume of air exhaled from a full lung (total lung capacity [TLC]) to maximal expiration (residual volume [RV]). This volume, the forced vital capacity (FVC) and the forced expiratory volume in the first second of the forceful exhalation (FEV1), should be repeatable to within 0.15 L upon repeat efforts in the same measurement unless the largest value for either parameter is less than 1 L. In this case, the expected repeatability is to within 0.1 L of the largest value. The patient is instructed to inhale as much as possible and then exhale rapidly and forcefully for as long as flow can be maintained. The patient should exhale until one of the criteria defining the end of a forced exhalation has been reached. At the end of the forced exhalation, the patient should again inhale fully as rapidly as possible. The FVC should then be compared with that inhaled volume to verify that the forced expiratory maneuver did start from full inflation.
Reduction in FEV1 may reflect reduction in the maximum inflation of the lungs (TLC); obstruction of the airways; respiratory muscle weakness; or submaximal expiratory force due to poor coaching, poor understanding, or malingering. Airway obstruction is the most common cause of reduction in FEV1. Airway obstruction may be secondary to bronchospasm, airway inflammation, loss of lung elastic recoil, increased secretions in the airway, or any combination of these causes. Response of FEV1 to inhaled bronchodilators is used to assess the reversibility of airway obstruction, although it is now widely appreciated that a response showing a lack of a significant increase in FEV1 does not indicate the patient will not benefit clinically from bronchodilator therapy. A significant increase in the inspiratory capacity (IC) and/or vital capacity (VC) after bronchodilator therapy can occur even when the FEV1 fails to show a significant change.[1]
The standards used to describe the quality of spirometry measurements are from the Standardization of Spirometry 2019 Update.[2] This document provides examples of the most common technical problems associated with spirometry testing. See Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement for more information.
Indications
Spirometry is used to establish baseline lung function, evaluate dyspnea, detect pulmonary disease, monitor effects of therapies used to treat respiratory disease, evaluate respiratory impairment or disability, evaluate operative risk, and perform surveillance for occupational-related lung disease. It may also be used in research and clinical trials and epidemiological surveys.
Contraindications
Relative contraindications (no absolute contraindications) for spirometry are as follows:
• Conditions that may be negatively impacted by the increases in myocardial demand or changes in blood pressure associated with spirometry: These include recent (< 1 week) myocardial infarction, systemic hypotension or severe hypertension, significant atrial/ventricular arrhythmia, noncompensated heart failure, uncontrolled pulmonary hypertension, acute cor pulmonale, clinically unstable pulmonary embolism, and a history of syncope associated with forced exhalation.
• Conditions that may be negatively impacted by the increase in intracranial/intraocular pressure associated with spirometry: These include cerebral aneurysm, recent (< 4 weeks) brain surgery, recent concussion with continuing symptoms, and recent (within 1 week) eye surgery.
• Conditions that may be negatively impacted by increased sinus and middle ear pressures: Examples include recent (< 1 week) sinus or middle ear surgery or infections.
Conditions that may be negatively impacted by increased intrathoracic and intraabdominal pressures: Examples include the presence of pneumothorax, recent (< 4 weeks) thoracic or abdominal surgery, and late-term pregnancy.                                                              • Infection control issues, including active or suspected transmissible respiratory or systemic infections
tuberculosis, or physical conditions predisposing to transmission of infections such as hemoptysis, significant secretions or oral lesions or bleeding.

Patient care/preparations
Two choices are available with respect to bronchodilator and medication use prior to testing. Patients may withhold oral and inhaled bronchodilators to establish baseline lung function and evaluate maximum bronchodilator response, or they may continue taking medication as prescribed. If medications are withheld, a risk of exacerbation of bronchial spasm exists.
Interpretation
Interpretation of spirometry results should begin with an assessment of test quality. Failure to meet performance standards can result in unreliable test results (see the image below). The American Thoracic Society (ATS) defines acceptable spirometry as an expiratory effort that has the following characteristics:
Pulmonary function tests require patients to successfully perform respiratory maneuvers in a standardized manner in order to obtain clinically meaningful results. Spirometry is perhaps the most technically and physically demanding. The patient is required to inhale as fully as possible, exhale with as much force as possible, and continue their expiratory effort until they empty their lungs as completely as possible or are unable to continue.
The performance standards for acceptable spirometry are summarized below. The comments of the technologist administering the test can assist the interpreting physician in determining if results of a testing session that fail to meet some of the standards can still provide clinically useful data

Age > 6 y: Difference between two largest FVC values must be <0.150 L, and the difference between two largest FEV1 values must be <0.150 L
Age <6 y: Difference between two largest FVC values must be <0.100 L or 10% of the highest value, whichever is greater, and the difference between two largest FEV1 values must be <0.100 L or 10% of the highest value, whichever is greater aFor children <6 y, must have at least 0.75 s of expiration without glottis closure or cough for acceptable or usable measurement of FEV0.75.
bOccurs when the patient cannot expire long enough to achieve a plateau (eg, children with high elastic recoil or patients with restrictive lung disease) or the patient inspires or comes off the mouthpiece before a plateau. For within-maneuver acceptability, the FVC must be larger than or within the repeatability tolerance of the largest FVC observed before this maneuver within the current prebronchodilator or the current postbronchodilator testing set.
cAlthough the performance of a maximal forced inspiration is strongly recommended, its absence does not preclude a maneuver from being judged acceptable, unless extrathoracic obstruction is specifically being investigated.

Characteristics of acceptable spirometry efforts are as follows:
• The patient is vigorously coached to inspire rapidly to full inflation.
• The patient shows minimal hesitation at the start of the forced expiration (extrapolated volume < 5% of FVC or 0.10 L, whichever is larger).
• The patients show an explosive start of the forced exhalation (rise time to peak flow no greater than 0.150 s). Rise time to peak flow is not available on all spirometers. If it is not available, it is not part of the assessment of the acceptability of the start of the forced exhalation.
• The patient shows no evidence of cough or artifact in the first second of forced exhalation.
• The results meet one of three criteria that define a valid end-of-forced exhalation: (1) smooth curvilinear rise of the volume-time tracing to a plateau (plateau defined as < 0.025 L volume change in the last 1 s of expiration ) of at least 1 second's duration; (2) if a forced test fails to exhibit an expiratory plateau, a forced expiratory time of 15 seconds; or (3) the FVC is within the repeatability tolerance of or is greater than the largest prior observed FVC.
• Upon completing the forced exhalation, the patient is coached to rapidly (> 2 L/s flow) inhale to full inflation upon completing the forced exhalation providing a value for forced inspiratory vital capacity (FIVC). The maximum FIVC can be no more than 0.100 L or 5% of the FVC larger than the FVC (whichever is greater). If the maximum FIVC is more than 0.100 L or 5% of the FVC greater than the FVC, that effort is not acceptable and cannot be used for reporting of any parameters.
• Repeatability of the largest FVC and FEV <| within 0.150 L (within 0.100 L if age < 6 y) is demonstrated in at least two efforts.

In patients who have significant loss of lung elastic recoil (pulmonary emphysema, COPD), spirometry may show negative effort dependence of forced expiratory flow. The effort that has the highest peak expiratory effort may produce a lower FEV1 because of the dynamic compression of the airways that results from the loss of elastic recoil support of airways that is characteristic of emphysema. In this circumstance, reporting the highest FEV1 coming from an effort with submaximal expiratory effort can lead to confusing results, particularly if a setting of assessing spirometric response to bronchodilators. Although not yet a spirometry acceptability standard, it appears that when reporting the FEV1 considering only efforts that have a time to peak flow (TPEF) less than or equal to 0.12 seconds helps eliminate this effect. This parameter can be displayed on most laboratory-based spirometry testing systems.
Inspection of the volume-time tracing aids in identification of early termination of expiration by evaluating the presence of an expiratory plateau. In the absence of an expiratory plateau, a 15-second expiratory time ensures the quality of the FVC. Inspection of the start of the volume-time tracing can help identify a hesitant start, which can result in a falsely low FEV1. Repeatability of the FVC and the FEV1 helps ensure that the results truly represent the patient's lung function. Attention should be focused on the repeatability of two key parameters: FVC and FEV1. It should be noted that while repeatability of the FVC and FEV1 strengthens the confidence that the forced exhalations started from full inflation, it is possible to demonstrate repeatability of these parameters even when forced exhalations start from a lung volume below full inflation. Demonstration that the difference between the largest FIVC and the FVC is no more than the larger of 0.100 L or 5% of the largest FIVC is a key acceptability criterion.
The reference equations published in 2012 by the Global Lung Initiative (GLI), a Task Force of the European Respiratory Society, provide normative values for males and females from age 3 to 95 years across a wide range of ethnicities,[3] and these should be used as the default set of reference values for spirometry. The use of these predicted values for spirometry has been supported globally, including endorsements from the European Respiratory Society, the ATS, the American College of Chest Physicians, the Thoracic Society of Australia and New Zealand, the Australian and New Zealand Society of Respiratory Science, and the Asian Pacific Society for Respirology. The report is in accordance with the previously published recommendations of the ATS that called for the elimination of a fixed percentage of predicted cut point to determine normality and a fixed lower limit of normal of the FEV1/FVC ratio to identify airway obstruction, both of which have been shown to result in significant misclassification of spirometry results. Guidelines for a standardized report format have been published and should be the default report format. The use of Z scores to determine the severity of spirometric abnormalities is encouraged.
Abnormalities can be classified by the physiological patterns outlined below.

Obstructive defects
Disproportionate reduction in the FEV1 as compared with the FVC is reflected in the FEV1/FVC ratio and is the hallmark of obstructive lung diseases. This physiologic category of lung diseases includes but is not limited to asthma, acute and chronic bronchitis, emphysema, bronchiectasis, cystic fibrosis, and bronchiolitis. The forced expiratory flow at any given lung volume is reduced. The mechanism responsible for the reduction in airflow can be bronchial spasm, airway inflammation, increased intraluminal secretions, and/or reduction in parenchymal support of the airways due to loss of lung elastic recoil. Poor understanding and effort on the part of the patient is also a cause for reduced flows, and the diagnosis of airway obstruction should be limited to measurements composed of acceptable efforts demonstrating repeatability of FVC and FEV1.
The use of a fixed lower limit of normal for the FEV1/FVC ratio as proposed by the Global Initiative for Obstructive Lung Disease (GOLD) lacks a scientific basis and results in significant misclassification of patients at either end of the age spectrum. Young patients are classified as "normal" when airflow obstruction is present, and older patients are classified as showing obstruction when no airflow obstruction is present. The use of the GOLD threshold for identifying airway obstruction should be discouraged in clinical practice where or when computerized predicted values are available.
The recommended practice for identifying a spirometric abnormality is to use the predicted lower limit of normal for that individual based on sex, age, height, and ethnicity. The GLI reference equations provide lower limits of normal for spirometric parameters.

Sient of reversibility of airway obstruction
ay obstruction is identified on spirometry, assessing response to inhaled bronchodilators is useful. The ATS has ded that the threshold for significant response be demonstration of an increase of at least 12% and 0.2 L in either FVC (provided the expiratory time for both sessions agree within 10%) or FEV1 on a spirogram performed 10-15 minutes after inhalation of a therapeutic dose of a bronchodilating agent. New standards recommend the use of four inhalations (100 meg each, 400 meg total dose) of albuterol administered through a valved spacer device. When concern about tremor or heart rate exists, lower doses may be used. Response to an anticholinergic drug may be assessed 30 minutes after four inhalations (40 meg each, 160 meg total dose) of ipratropium bromide. Failure to respond to bronchodilator challenge does not preclude clinical benefit from bronchodilators. A positive response to the bronchodilators may correlate with response to steroid therapy.

Restrictive defects
Reduction in the FVC with a normal or elevated FEV1-to-FVC ratio should trigger further evaluation of total lung capacity (TLC) to rule out restrictive lung disease. Measuring the TLC and residual volume (RV) can confirm restriction suggested by spirometry
Normal aging results in an increase in functional reserve capacity (FRC) and residual volume (RV) and a normal total lung capacity (TLC) percentage. Obstructive lung diseases cause hyperinflation (increase in RV and FRC) with a relatively normal forced vital capacity (FVC). In severe emphysema, the TLC percentage can exceed 150%, with the RV impinging on the FVC. Restrictive lung diseases exhibit reduced TLC percentage with relative preservation of the RV/TLC percentage in fibrosis, a reduced inspiratory capacity and expiratory reserve volume (ERV) in neuromuscular disease, and severe reduction of the ERV in extreme obesity.

Quantification of impairment by spirometry
In normal spirometry, FVC, FEV1, and FEV1 -to-FVC ratio are above the lower limit of normal. The lower limit of normal is defined as the result of the mean predicted value (based on the patient's sex, age, and height) minus 1.64 times the standard error of the estimate from the population study on which the reference equation is based. If the lower limit of normal is not available, the FVC and FEV1 should be greater than or equal to 80% of predicted, and the FEV1 -to-FVC ratio should be no more than 8-9 absolute percentage points below the predicted ratio. The ATS has recommended the use of lower limits of normal instead of the 80% of predicted for setting the threshold that defines abnormal test results.
A reduced FVC on spirometry in the absence of a reduced FEV1/FVC ratio suggests a restrictive ventilatory problem. An inappropriately shortened exhalation during spirometry can (and often does) result in an artifactually reduced FVC. Causes of restriction on spirometry include obesity, cardiomegaly, ascites, pregnancy, pleural effusion, pleural tumors, kyphoscoliosis, pulmonary fibrosis, neuromuscular disease, diaphragm weakness or paralysis, space-occupying lesions, lung resection, congestive heart failure, inadequate inspiration or expiration secondary to pain, and severe obstructive lung disease. One scheme for describing the severity of reductions in the FVC and/or the FEV1 is shown below:
• Mild - Greater than 70% of predicted
• Moderate - 60-69% of predicted
• Moderately severe - 50-59%
• Severe - 35-49% of predicted
• Very severe - Less than 35% of predicted

The lower limit of normal for the FEF25-75% can be less than 50% of the mean predicted value, making it important to use the lower limit of normal defined by the 95% confidence limit of the mean predicted value rather than a threshold defined by a fixed percentage of the predicted value. The FEF25-75% is also very dependent on expiratory time. If expiratory times of spirometry efforts vary by more than 10%, comparisons of the FEF25-75% before and after bronchodilator challenge are difficult to Early termination of expiration shifts the middle 50% of the exhaled volume towards the start of the exhalation, ill raising the FEF25-75%. For these reasons, the use of the FEF25-75% to assess airway function in adults is indicated.

The lower limit of normal for the FEF25-75% can be less than 50% of the mean predicted value, making it important to use the lower limit of normal defined by the 95% confidence limit of the mean predicted value rather than a threshold defined by a fixed percentage of the predicted value. The FEF25-75% is also very dependent on expiratory time. If expiratory times of spirometry efforts vary by more than 10%, comparisons of the FEF25-75% before and after bronchodilator challenge are difficult to Early termination of expiration shifts the middle 50% of the exhaled volume towards the start of the exhalation, ill raising the FEF25-75%. For these reasons, the use of the FEF25-75% to assess airway function in adults is indicated. The FVC is a reliable means of assessing the clinical status in idiopathic pulmonary fibrosis (IPF). A minimum clinically important difference of the FVC, expressed as a percentage of the mean predicted normal value, of 2-6% has been established. This obviates the need to obtain a total lung capacity (TLC) measurement to assess disease progression or the effects of medical therapy.

Special assessments
Sitting versus supine vital capacity
Evaluation of diaphragm strength can be accomplished by measuring the vital capacity in an upright or sitting position followed by a measurement made in the supine position. A reduction in the vital capacity to less than 90% of the upright vital capacity suggests diaphragm weakness or paralysis. Interpreting an increased reduction in vital capacity in the supine position as diaphragm dysfunction should be made cautiously if the patient's body mass index is greater than 45 kg/m2.[4] Studies reporting the normal reduction of the vital capacity of less than 10% from upright to supine were conducted with individuals who were not obese. Slightly greater reductions in obese individuals in a supine position may not indicate diaphragm dysfunction, but rather an increase in the resistive forces against which the diaphragm descends. Reductions in the supine vital capacity more than 20% of baseline indicate hemidiaphragm or diaphragm dysfunction or paralysis.
Identifying central airway obstructions
The configuration of the flow-volume curve of a properly performed spirometry test can be used to demonstrate various abnormalities of the larger central airways (larynx, trachea, right and left mainstem bronchi). Three patterns of flow-volume abnormalities can be detected: (1) variable intrathoracic obstructions, (2) variable extrathoracic obstructions, and (3) fixed upper airway obstructions. Reproducing these findings on every effort is important because spurious nonreproducible reductions in inspiratory flow are not uncommon after completion of forced expirations in subjects without upper airway obstruction. Examples of variable intrathoracic obstruction include localized tumors of the lower trachea or mainstem bronchus, tracheomalacia, and airway changes associated with polychondritis.
Variable upper airway obstructions demonstrate flow reductions that vary with the phase of forced respirations. Variable intrathoracic obstructions demonstrate reduction of airflow during forced expirations with preservation of a normal inspiratory flow configuration. This is observed as a plateau across a broad volume range on the expired flow limb of the flow-volume curve. The reduction in airflow results from a narrowing of the airway inside the thorax, in part because of a narrowing or collapse of the airway secondary to extraluminal pressures exceeding intraluminal pressures during expiration.
Variable extrathoracic obstructions demonstrate reduction of inspired flows during forced inspirations with preservation of expiratory flows. Again, the major cause of the reduced flow during inspiration is airway narrowing secondary to extraluminal pressures exceeding intraluminal pressures during inspiration. Causes of this type of upper airway obstruction include unilateral and bilateral vocal cord paralysis, vocal cord adhesions, vocal cord constriction, laryngeal edema, and upper airway narrowing associated with obstructive sleep apnea. Fixed upper airway obstructions demonstrate plateaus of flow during both forced inspiration and forced expiration. Causes of fixed upper airway obstruction include goiters, endotracheal neoplasms, stenosis of both main bronchi, postintubation stenosis, and performance of the test through a tracheostomy tube or other fixed orifice device. Flow reduction must be consistent on every effort to be considered actual flow limitation. Fixed upper airway obstruction may be caused by postintubation stenosis, goiter, endotracheal neoplasms, and bronchial stenosis. Variable intrathoracic obstruction may be caused by tracheomalacia, polychondritis, and tumors of the lower trachea or main bronchus. Variable extrathoracic obstruction may be caused by bilateral and unilateral vocal cord paralysis, vocal cord constriction, reduced pharyngeal cross-sectional area, and airway burns. While no single test can effectively predict intraoperative and postoperative morbidity and mortality from pulmonary complications, the FEV1 obtained from good quality spirometry is a useful tool. When the FEV1 is greater than 2 L or 50% of predicted, major complications are rare.
Operative risk is heavily dependent on the surgical site, with chest surgery having the highest risk for postoperative complications, followed by upper and lower abdominal sites. Patient-related factors associated with increased operative risk for pulmonary complications include preexisting pulmonary disease, cardiovascular disease, pulmonary hypertension, dyspnea upon exertion, heavy smoking history, respiratory infection, cough (particularly productive cough), advanced age (>70 y), malnutrition , general debilitation, obesity, and prolonged surgery.
Assessment for lung surgery typically involves prediction of a postoperative FEV1 by using the preoperative FEV1. In a borderline case, consideration of the contribution of the remaining portions can be assessed by a perfusion scan. The relative percentage of perfusion (Q) of the remaining lung or lung segments usually is proportional to its contribution to ventilation and can be used to estimate postoperative function as shown in the following equation:
Postoperative FEV1 = Preoperative FEV1 x Q% of the remaining lung
For example, if the preoperative FEV1 is 1.6 L and the lung to be resected demonstrates 40% perfusion, the postoperative FEV1 would be 1.6 x 0.6 = 0.96 L. An estimated postoperative FEV1 of less than 0.8 L is often associated with chronic respiratory failure and may indicate an unacceptable degree of operational risk. Arterial blood gases (ABGs) and cardiopulmonary exercise testing may help evaluate operative risk in patients who have a preoperative FEV1 below 2 L or 50% of predicted.
The algorithm for clearance of candidates for lung resection proposed by Bolinger and Perruchoud[5] has been successfully evaluated in 137 consecutive patients who were referred for resection by Wyser et al[6] with an overall mortality of 1.5% and is detailed in Cardiopulmonary Stress Testing. Patients with a negative cardiac history and ECG that demonstrate an FEV1 and a diffusing capacity of lung for carbon monoxide (DLCO) that are greater than 80% of predicted are judged to be able to undergo pneumonectomy safely.

Lung Volume Determination
Synonyms
Functional reserve capacity (FRC), helium dilution lung volumes, nitrogen washout lung volumes, static lung volumes, lung subdivisions
Indications
Lung volume determinations are used in the evaluation of suspected restrictive lung disease and the evaluation of hyperinflation.
Contraindications
Inability to follow instructions is a contraindication. Patients with claustrophobia may not tolerate being closed into a confined space (body plethysmograph), but anxiety can often be overcome with good instruction and coaching.

Diffusing Capacity of Lung for Carbon Monoxide
Synonyms
Transfer factor of the lung for carbon monoxide (TLCO, mmol/min/kilopascal, commonly used in Europe); DLCO, diffusing capacity of lung for carbon monoxide (DL, mL/min/mmHg); transfer coefficient of the lung for carbon monoxide (KCO); and alveolar volume (VA, L), which is the single-breath estimate of the TLC determined by the dilution of the tracer gas concentration. The term KCO should be used instead of the term DLCOA/A, which incorrectly implies that the DLCO is being corrected for lung volume.
Contraindications
Inability to follow instructions is a contraindication to a DLCO test (CPT code 94729). Patients should be alert, oriented, able to exhale completely and inhale to total lung capacity, able to maintain an airtight seal on a mouthpiece, and able to hold a large breath for 10 seconds.
Patient care/preparations
Refrain from smoking for several hours before the test. Alcohol vapors can affect the accuracy of some fuel cell types of CO analyzers, thus alcoholic beverages should be withheld for eight hours.
Test
DLCO, also known as the TLCO, is a measurement of the conductance or ease of transfer for CO molecules from alveolar gas to the hemoglobin of the red blood cells in the pulmonary circulation. It is often helpful for evaluating the presence of possible parenchymal lung disease when spirometry and/or lung volume determinations suggest a reduced vital capacity, RV, and/or TLC. It should be noted that different units of measure exist worldwide. In the United States, the test is known as the DLCO and the units of measure are mL/min/mm Hg (traditional unit of measure). In contrast, the test is also known as the TLCO and the units of measure are mmol/min/kPa (International System of Units or SI units). The conversion from SI units (mmol/min/kPa) to traditional (mL/min/mm Hg) can be done by multiplying the SI value by 2.987.
Recommendations for a standard technique for the test were first published by the American Thoracic Society (ATS) in 1995. A joint task force from the ATS and the European Respiratory Society (ERS) published updated standards in 2017.[7] The updated standards include some important changes in the criteria used to determine the technical acceptability and expected repeatability of measurements, as well as recommendations on the increased utility of the procedure when rapid-responding gas analyzer (RGA) technology is used. RGA technology has been available for over a decade and most commercial equipment currently sold uses the RGA technology. It is likely that most of the slower-responding analyzer technology will be phased out by equipment replacement over the coming decade.
Most pulmonary laboratories perform this test by the single-breath technique (DLCO SB) because it is quicker to perform and more reproducible than other techniques. Other techniques, such as the rebreathing technique, are not commonly available and are not described here. In the single-breath technique, the subject exhales to RV and then inhales the test gas (tracer gas, [commonly either 10% helium or 0.3% methane], 0.3% CO, 21% oxygen, and balance nitrogen) briskly to TLC. This vital capacity-size breath is held for 10 seconds and then exhaled either into a sample bag (discrete sampling) or past a sampling port leading to rapid-response analyzers after an initial discard of 0.75-1 L of the exhale to minimize the contribution of dead space gas (mouthpiece, filter, measuring equipment, and anatomical areas where no gas exchange is expected) to the gas sample that will be analyzed to estimate uptake of CO by the alveolar capillaries. The grab sample (0.75-1 L) is then analyzed gas and CO. The dilution of the tracer gas in the vital capacity-size breath of test gas by the patient's RV provides means to estimate the initial alveolar concentration of CO and to estimate the patient's lung volume at full inflation. The ffusion of the CO can be estimated by the change from this initial alveolar concentration to that of the expired grab. This change in the CO concentration is then multiplied by the single-breath estimate of TLC to calculate the diffusing capacity. Abnormal hemoglobin (Hb) levels can affect the diffusing capacity and, if known, should be used to mathematically correct the measured diffusing capacity to what it would be if the patient's hemoglobin was normal. Although it has been recommended that the predicted value be adjusted for hemoglobin,[7, 8] providing an estimate of what the patient's expected DLCO should be given their hemoglobin level, equipment manufacturers have been slow to offer this accommodation in the testing software and the older practice of adjusting the patient's measured DLCO to what it would be if their hemoglobin was normal is still quite common. Both methods are presented below. Both methods yield identical values when the measured values are compared with the predicted values and expressed as a percentage of the predicted value. Regardless of whether the measured or predicted values are adjusted, both adjusted and unadjusted values should be displayed on the final report, along with the measured hemoglobin (and date of hemoglobin determination).
Adjusting the patient's measured DLCO value for the measured hemoglobin (not currently recommended but still commonly used) is as follows:
• Adolescent males and men: Hb adjusted DLCO (DLCOc) = measured DLCO ([10.22 + Hb g/dL]/[1.7 Hb])
• Children younger than 15 years and women: Hb adjusted DLCO (DLCOc) = measured DLCO ([9.38 + Hb g/dL]/[1.7 Hb])
Adjusting the predicted DLCO (and lower limit of normal) for the patient's measured hemoglobin (currently recommended) is as follows:
• Adolescent males and men: DLCO (predicted for Hb) = DLCO (predicted) x (1.7 Hb/(10.22 + Hb))
• Children younger than 15 years and women: DLCO (predicted for Hb) = DLCO (predicted) x (1.7 Hb/(9.38 + Hb))
Other factors have been shown to impact the measured DLCO, such as elevated blood carboxyhemoglobin (COHb) and barometric pressure. The impact of an elevated carboxyhemoglobin is twofold: (1) it reduces the alveolar-capillary pressure gradient for CO and (2) acts as a virtual anemia by holding onto sites on the hemoglobin molecule that could be used for binding CO (or oxygen) . The net effect is a 2% decrease in DLCO for each 1% increase in COHb. RGA systems can measure the CO in the patient's exhaled breath just prior to inhalation of the DLCO test gas and compensate for elevated CO by subtracting the estimated CO back-pressure from both the initial and final alveolar carbon monoxide partial pressures. This compensates for the reduced alveolar-capillary pressure gradient but does not compensate for the anemia effect. The 2017 DLCO standards paper shows a formula that also adjusts for the anemia effect, but this is not currently in use on most PFT systems.
The current recommendation is to correct the measured DLCO for barometric pressure. As barometric pressure falls, so does the partial pressure of inspired oxygen (PI02) and DLCO increases. The typical variation in DLCO expected from atmospheric pressure fluctuation at a given altitude is +1.5%. Laboratories at higher altitude can produce higher values; the expected change is approximately 0.5% for each 100-meter increase in altitude. This adjustment can only be made if the barometric pressure is made or updated in the measuring system on a daily basis.

Quality grading for DLCO maneuvers
The 2017 ATS/ERS DLCO standards paper specified changes to the acceptability and repeatability standards used to determine technical acceptability.^] It also proposed a quality control grading system that acknowledges that test results from efforts that fail to meet all of the acceptability criteria may still provide clinically useful data.
The 2017 criteria for acceptability of DLCO efforts are as follows:
• VI (inspired volume of test gas) greater than 90% of the largest VC measured by same-day slow or forced spirometry (2005 standard was >85%) or
• VI greater than 85% of largest VC and alveolar volume (VA) within 0.2 L or 5% (whichever is greater) of the largest VA from other acceptable maneuvers
• 85% of test gas VI inhaled in less than 4 seconds (unchanged from 2005 standards)
• Breathe hold time of 10 + 2 seconds without evidence of significant leaks, Valsalva maneuver, or Mueller maneuver (unchanged from 2005 standards)
• Sample collection completed within 4 seconds of the start of exhalation (was 3 seconds in 2005 standards); for RGA systems, virtual sample collection should be initiated after dead-space washout is complete
The 2017 criterion for DLCO repeatability is as follows:
• At least two acceptable DLCO measurements within 2 mL/min/mm Hg (0.67 mmol/min/kPa) of each other (2005 standard was 3 mL/min/mm Hg or 1 mmol/min/kPa)

Quality grading for DLCO measurements is as follows:
• Score of A: (1) VI/VC 90% or VI/VC greater than 85% and VA within 0.2 L or 5% of largest VA from another acceptable aneuver; (2) breath hold time of 8-12 seconds; and (3) sample collection less than 4 seconds blore of B: (1) VI/VC greater than 85%; (2) breath hold time of 8-12 seconds; and (3) sample collection less than 4 icons
• Score of C: (1) VIA/C greater than 80%; (2) breath hold time of 8-12 seconds; and (3) sample collection less than 5 seconds
• Score of D: (1) VIA/C greater than 80%; (2) breath hold time of less than 8 seconds or greater than 12 seconds; and (3) sample collection less than 5 seconds
• Score of F: (1) VI/VC less than 80%; (2) breath hold time of less than 8 seconds or greater than 12 seconds; and (3) sample collection greater than 5 seconds
Only grade A maneuvers meet all acceptability criteria. The average DLCO values from two or more grade A maneuvers that meet the repeatability criterion should be reported. If only one grade A maneuver is obtained, the DLCO value from that maneuver should be reported. If no grade A maneuver is obtained, maneuvers of grades B to D might still have clinical utility, and the average of such maneuvers should be reported. However, these deviations from the acceptability criteria must be noted to caution the interpreter of the test. Maneuvers of grade F are not usable.

Results
The 2017 ATS recommendations for a standardized pulmonary function report details recommendations for reporting of DLCO. A major change is the recommendation to express the measured DLCO on a z-score scale, which expresses the result as the number of multiples of a standard deviation above or below a population mean.
When hemoglobin is measured and available, it should be shown on the report with a note indicating whether the measured or predicted value has been adjusted for this.

Interpretation
Because the DLCO is directly proportional to VA (VA is the lung volume after inhalation of the DLCO test gas, based on the size of the breath of test gas and the dilution of the inspired tracer gas). Nonpulmonary processes that reduce the lung volume at full inflation cause reductions in the DLCO. If VA can be assessed accurately, these reductions produce a normal or elevated KCO. Examples of this include lung resection, thoracic cage abnormalities (eg, kyphoscoliosis), and small lungs. DLCO is reduced in pulmonary emphysema. However, because of the poor distribution of the inspired test gas, the VA may grossly underestimate the TLC, and the resulting KCO may be normal. A reduced DLCO and a reduced KCO suggest a true interstitial disease such as pulmonary fibrosis or pulmonary vascular disease. It has demonstrated that in healthy patients, the KCO is increased to above normal levels when the DLCO test is performed at volumes less than the TLC.
The pattern of a low DLCO and a normal KCO may not be sufficient to rule out the presence of parenchymal disease. The works of Johnson[9] and Chinn et al[10] advocate the volume correction of the predicted value for DLCO by using the measured VAto "correct" the predicted DLCO for low or high lung volumes. Further work is warranted, but studies demonstrating the nonlinearity of the relationship between lung volume and DLCO are sufficiently convincing that the practice of interpreting a low DLCO and a normal KCO (previously known as DLCO/VA) as "normal" is discouraged. The degree of severity of reduction in the diffusing capacity can be assigned according to the following scheme: less than the predicted lower limit of normal but greater than 60% of predicted is mild, between 40% and 60% of predicted is moderate, and less than 40% is severe.
Nonperfusion of ventilated alveoli, such as in pulmonary vascular disease, produces a reduction of both the DLCO and the KCO. Anemia produces a virtual reduction in pulmonary capillary blood volume that causes a reduction in DLCO that can be adjusted mathematically for the reduced hemoglobin. The DLCO may be reduced temporarily in a variety of disorders such as pneumonia, interstitial infiltrative disorders, and alveolar proteinosis. The importance of obtaining an inspiratory vital capacity (IVC) greater than 90% of the best measured VC from the day of the test cannot be overemphasized. Inability to achieve an IVC of greater than or equal to 90% of the largest VC measured that day must be noted on the report.