Pulmonary function testing for pathologists


As the name implies, pulmonary function testing provides quantification of pulmonary physiologic function. By definition this information is disease independent and static, representing a point-in-time evaluation.

Nonetheless, this information can be very helpful for building a differential diagnosis. In fact, many pulmonary diseases are clinical syndromes and without either a definitive molecular marker for disease or without unique defining functional features. These diseases therefore often require integration of histopathology with radiologic patterns, clinical context, and functional status. Pulmonary function tests (PFTs) often provide the first diagnostic tool that helps guide a clinical pulmonologist in creating a filing system for a possible differential. This chapter will focus on the basic elements that comprise a full set of PFTs. In general, these consist of lung volumes (TLC, FRC, RV; see Table 2.1 for a list of abbreviations used in this chapter), lung flows by spirometry (FVC, FEV1, FEF 25-75 ), airway resistance (R aw ), and capillary bed assessment (DLCO). Correct interpretation of PFTs requires that the patient-obtained values be read in comparison with appropriate reference values, resulting in a reporting method of “percent of predicted.” Numerous regression equations have been proposed, and used, all commonly adjust for age, sex, height, and race. The European Respiratory Society and the American Thoracic Society have published guidelines regarding the conduct of measuring and interpreting PFTs. ,

Table 2.1
Common Pulmonary Function Test Terminology
TLC total lung capacity The volume in the lungs at maximal inflation TLC = RV + VC = FRC + IC
FRC functional residual capacity The volume in the lungs at end expiration
RV residual volume The volume that remains after full exhalation
ERV expiratory reserve volume The volume that remains after normal tidal respiratory exhalation above the RV
IRV inspiratory reserve volume The maximal additional inhalable volume starting after a normal tidal volume IRV = IC − TV
IC inspiratory capacity The maximal volume for inhalation starting at FRC IC = TV + IRV
IVC inspiratory vital capacity
VC vital capacity The total available volume from RV to TLC TLC − RV = VC
TV tidal volume The normal respiratory cycle volume
FVC forced vital capacity Maximal volume attained on dynamic forced expiration beginning at TLC
FEV1 forced expiratory volume in first second Maximal volume attained on forced exhalation in first second
FEV1/FVC the ratio of the % predicted Reveals if increased or decreased flows
NIF negative inspiratory force Reveals force generated on inspiration
PEF positive expiratory force Reveals force generated on expiration
DLCO diffusion capacity of carbon monoxide Measures the uptake of CO as surrogate for capillary beds

Furthermore, PFTs provide quantification of the severity of the lung impairment and can be used to evaluate for change in lung function over time. This change over time in function may be age related or represent deterioration related to a disease state or, potentially, improvement related to institution of therapy.

The approach of this chapter is therefore to outline how the functional data from PFTs can help guide that differential. Fundamentally, lung physiologic function will be normal, restrictive, or obstructive. Restriction implies reduction in lung volumes—size of the lungs. Obstructive implies reduced air flows, mostly secondary to narrowing of the airways, such as in asthma, or reduced elastic recoil, such as from emphysema, leading to greater exhalation times. We will start with simple categorization of normal compared with restrictive and obstructive patterns.

Although patterns may be mixed, for purposes of organization, one must be predominant. In truth, many techniques and a plethora of available equipment make this arena very diverse. Therefore each part has pros and cons and must be considered in the interpretation of PFTs. After all the parts are established, pattern recognition is a key element, as with many composite tests in medicine.

This chapter seeks to provide a clear understanding of the fundamentals of PFTs. Basic interpretation should allow the pathologist to independently provide additional functional context to their differentials on evaluation of histopathology of lung tissue to better inform the clinician for a diagnosis.

Lung volumes

The first objective of a full set of PFTs involves determination of the size of the lungs or the lung volumes. Almost all pulmonary diseases that affect function can be divided into three simple categories. Obstructive lung diseases will all eventually lead to increased lung volumes. This is because ultimately air gets in but cannot get back out. This effect can result in static air trapping, such as in emphysema, or dynamic air trapping, as in reversible airway disease like asthma. Restrictive lung diseases will all lead to some measure of reduction in lung volumes because the lung themselves are stiffer or the chest wall either will not allow for expansion (i.e., chest wall restriction) or cannot expand fully (i.e., neuromuscular weakness ). Normal lung size implies no clinical deficit from obstruction or restriction. This leaves the pulmonary vasculature or, alternatively, causes external to the lung as potentially causal for any presenting symptomatology.

The lung volumes and lung capacities refer to volumes associated with different phases of the respiratory cycle. Although the volumes can be directly measured, the available capacities are inferred from the lung volumes.

There are a number of volumes that can be measured ( Table 2.1 and Fig. 2.1 ); however, three measures (TLC, FRC, RV) are key in determining restriction versus obstruction. The remaining volumes and capacities represent measures for compartmentalization of the respiratory cycle functions (IRV, TV, ERV, RV, IC, and VC).

Figure 2.1, The volumes of the lung are determined by the pressure-volume relationship between the chest wall, which exerts negative force on the intrathoracic shape as the ribs are built like a “bow” of a bow and arrow set, and the lung, which, like a balloon, has elastic recoil that exerts a positive force to keep it small. The neutral point is presented by the balance of these forces at the functional residual capacity (FRC) and where we spend the majority of our time when not actively inhaling or exhaling. ERV , Expiratory reserve volume; RV , residual volume; TLC , total lung capacity, TV , tidal volume.

Tools to measure volumes

There are several methodologies to attaining lung volumes. The gold standard involves body box plethysmography. This method uses Boyle’s law (PV = nRT) to measure changes in pressure to determine lung volumes, assuming the temperature is constant. Note that this measure is ideally conducted with the patient breathing normally and therefore measures the functional residual capacity (FRC). Determination of the total lung capacity and residual volume are therefore determined by simple algebraic addition of inspiratory capacity (FRC + IC = TLC) and subtraction of the vital capacity (TLC − VC = RV). Therefore these last two volumes should be interpreted in light of the quality of the IC and VC. Although this approach is the most accurate, it also involves the largest and most expensive piece of equipment. As a consequence many labs will use a closed-circuit technique with a helium dilution or nitrogen washout technique. These techniques make assumptions regarding the equilibration of gas concentrations in the portions of the lung that communicate with the breathing circuit. The key limitation of these last two approaches is that areas of the lung that involve trapped air (bullous disease in example) do not necessarily communicate with the breathing circuit and therefore result in an underestimation of the total volume.

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