The uncertainties of bronchoalveolar lavage.

Correspondence: R.P. Baughman, Pulmonary and Critical Care Medicine, University of Cincinnati Medical Center, PO Box 670564, Cincinnati, OH, USA Heisenberg noted that a more accurate determination of one quantity will result in a less precise measurement of another. He proposed this principle to describe the difficulties encountered in quantum mechanics, but it has been encountered in all branches of science. For example, placing a stethoscope on a patient's chest wall to hear better will lead to changes in the patient's respiratory pattern. This leads to different sounds heard on auscultation. In performing invasive procedures, the effect can be more dramatic and, unfortunately, is not predictable. Bronchoalveolar lavage (BAL) has been performed as a research and clinical procedure for more than 20 yrs [1]. It has proved a useful method to sample lower respiratory secretions. This sampling technique has increased our diagnostic sensitivity for infectious and noninfectious lung diseases. In inflammatory lung diseases, it has provided a method of measuring protein and cellular influx into the lung. The cascades of cytokines that occur in the lung during adult respiratory distress syndrome (ARDS) or sarcoidosis have been readily demonstrated by BAL. One difficulty of lavage is the variability in the recovery of fluid during the procedure. Figure 1 is a schematic representation of the lavage process. The fluid is instilled into the distal airway, which is the equivalent of a sac. This introduced fluid mixes with the air and lung lining fluid. Contamination of the alveolar space by upper airway secretion is possible, but is, apparently, a small problem. This may be due to the small volume of potential contamination from the upper airways (1–2 mL) versus the large volume of fluid instilled during the lavage (100–200 mL). The amount of mixing in the alveolar space has been difficult to determine, especially since the volume retrieved is never equal to the volume instilled. This incomplete retrieval of fluid means that the aspirated fluid contains an unknown amount of lung lining fluid. An external marker in the instilled fluid is one method of determining the volume of lung lining fluid that has been aspirated. Dilution of this external marker has been used in a similar manner to the helium dilution technique used to calculate lung volumes. By measuring the concentration of the marker in the instilled and aspirated fluid as well as the volume of aspirated fluid, it is possible to calculate the volume of lung lining fluid aspirated. A major assumption regarding the external marker is that it is not absorbed by the lung surface membrane. Helium has proved to be useful for measuring lung volumes since there is minimal absorption of this inert gas. Methylene blue was proposed as an external marker for measuring lung lining fluid volume [2]. However, methylene blue is taken up by macrophages and epithelial cells. Therefore, the concentration of methylene blue is reduced by a nondilutional pathway and the amount of lung lining fluid will be overestimated [3]. Some of the large molecular weight sugars have been proposed as external markers, but it will be necessary to show that they are not taken up by the metabolically active cells in the airways. An internal marker is a substance in the lung lining fluid that is not present in the introduced fluid. If the concentration of the marker in the lung lining fluid and aspirated fluid is known, as well as the volume of aspirated fluid, it is possible to calculate the volume of aspirated lung lining fluid. By selecting substances that are freely permeable into extravascular spaces, the concentration of the internal marker is assumed to be the same in the blood and the lung lining fluid. However, care must to be taken to avoid a marker that may be secreted or produced in the lung lining fluid, such as immunoglobulin (Ig) A, and would, therefore, not be a valid marker. Urea has been commonly used as an internal marker [4]. The major problem with internal markers is that they may cross into the fluid during the procedure. Since the concentration of the marker is zero in the introduced fluid, the lavage process will dilute the marker in the lung lining fluid. During the aspiration process, the marker may be secreted into the fluid. It has been shown that the total amount of urea aspirated increases significantly as the time to perform the aspiration increases. This increased amount will increase the concentration in the aspirated fluid [5–7]. This will be interpreted as an EDITORIAL