Albumin is not suitable as a marker of bronchoalveolar lavage dilution in interstitial lung disease

Abstract

We have investigated the origin of raised bronchoalveolar lavage (BAL) albumin levels in interstitial lung diseases (ILDs), and the hypothesis that acute flux during BAL might contribute to the elevated levels of albumin in samples from ILD patients.Total albumin concentrations were measured in three separately aspirated 60 mL aliquots of BAL in 12 ILD patients and seven control subjects, and previous work indicating that BAL albumin levels may be raised in ILD was confirmed. In addition, the extent of acute flux from the circulation was investigated using 1.48 MBq of 125 I-radiolabelled human serum albumin injected intravenously shortly before the procedure.It was found that acute albumin flux occurred in only a minority of the ILD patients (4 out of 12) and control subjects (3 out of 7). These results indicate that the elevated levels of plasma proteins, such as albumin, documented in BAL aspirates from ILD patients are not an artefact of the BAL procedure related to increased vascular permeability, and that this finding is more likely to be related to the effects of chronic inflammatory changes in the lung due to the underlying disease.The work confirms that albumin is unsuitable as a denominator for the normalization of bronchoalveolar lavage solute results, since levels can vary, both as a result of acute flux and, more frequently, because of disease activity.

The uncertainties of bronchoalveolar lavage

“…In the current issue of the Journal, WARD et al [11] report on albumin in the BAL fluid of patients with ILD.They demonstrated rapid transport of albumin into the lung of some, but not all, healthy volunteers, similar to their previous findings [10]. This supports their view that the lavage process can lead to leakage of serum albumin into the lung.…”

“…As WARD et al [11] pointed out, the lavage procedure itself affects the results. Also, the lung is an active organ, secreting and absorbing proteins and cells during the lavage procedure.…”

Increased soluble CD14 in bronchoalveolar lavage fluid of stable lung transplant recipients

“…In favour of local production are experiments showing upregulation of CD14 expression in pulmonary diseases characterized by chronic alveolar macrophage activation [21,22]. Using radioisotope flux studies in interstitial lung disease, the authors have suggested that elevated BAL albumin levels are related to local inflammation, rather than acute permeability changes due to the BAL procedure itself [18]. In favour of extravasation is the work of DUBIN et al [16], their study showed that apparently maximal rates of sCD14 release, from antigen-challenged BAL macrophages could only account for 2% of sCD14 found in BAL.…”

“…In a radioisotope study of patients with interstitial lung disease, the authors have suggested that BAL albumin levels were related to the effects of lung inflammation rather than acute flux from the serum [18]. A similar logic may apply in a study of LTR.…”

Efficacy of two breath condensers

“…Dilution of ELF by saline during a BAL process may vary (21) and a useful dilution marker has not been identified despite several trials (22,23). The lack of feasible reference substances incapacitates evaluation of the true local concentration of inflammation products in BL or BAL as well as in EBC.…”