| Type I and III procollagen propeptides in sarcoidosis, fibrosing alveolitis and asbestos-related lung diseases | ||
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Bronchoalveolar lavage is a diagnostic procedure of washing a sample of cells and secretions from the alveolar and bronchial airspaces. It is performed by installing commercial sterile 0.9% saline solution for intravenous use via a channel of a fiberoptic bronchoscope, which has been wedged into a bronchus with a matching diameter. The fluid is then immediately withdrawn. The instilled fluid fills the airspaces distal to the tip of bronchoscope, replacing the air. A portion of the installed volume remains to be absorbed or expectorated after the procedure. Saline solution is usually used at room temperature, and warming it up to 37°C does not involve any advantage. (Davis 1994). After withdrawal, the fluid should be kept on ice until it is further processed.
A major clinical limitation for the utility of bronchoalveolar lavage is the large range of normal values for each parameter, which makes BALF insensitive in detecting disease. Furthermore, abnormalities in BALF are rarely specific for any of the interstitial lung diseases. There are some subjects who have normal BALF constituents despite a definite disease and some without any evidence of disease despite abnormal BALF findings. There is large interindividual variation which may not be related to the disease, and the airspace cells and secretions may not reflect interstitial processes. The removal of BALF may preferentially select, activate or injure some cells, and the composition of the epithelial lining fluid (ELF) may change during the bronchoalveolar lavage. (Davis 1994).
The standard techniques for investigating the cells in bronchoalveolar lavage fluid include millipore filter preparations stained with Papanicolaou and cytocentrifuge preparations stained with May-Grünwald-Giemsa. A routine cytological examination of BALF includes the determination of total and differential cell counts, screening for foreign particles and microbes, and recognition and classification of cellular atypia. In the differential count used in routine diagnostic purposes, 200 consecutive cells are counted and expressed as percentages of the whole cell population. The proportion of red blood cells is used to evaluate blood contamination in BALF. (Taskinen et al. 1994).
The cell findings in BALF are non-specific in most of cases. An increased total amount of cells (>150 x106/l among non-smokers and >360 x106 /l among smokers) in BALF is common and can be seen with most diseases. Smoking causes a three- to fourfold increase in the total cell count, mainly because of increased macrophages. The highest concentrations (>800 x106/l) can be seen in acute bacterial infections, eosinophilic pneumonias and leukaemias and, a considerable increase (>400 x106/l) may appear in allergic alveolitis and infections. In sarcoidosis, the total amount of cells is typically only slightly elevated. A normal total count of cells in BALF can be seen in fibrosing alveolitis with a prolonged course, various fibrosing processes, cytomegalovirus infections in immunocompromised patients and treated or low-activity sarcoidosis. (Taskinen et al. 1994).
The pattern and numbers of cells recovered in fibrosing alveolitis are significantly abnormal. The absolute numbers of macrophages, neutrophils, eosinophils and basophils are usually increased, and lymphocytes are variably increased as well. The percentages of neutrophils, eosinophils, basophils and sometimes lymphocytes are increased, thus diminishing the percentage of macrophages. An elevated fraction of lymphocytes has been associated with a good prognosis and response to therapy, while elevated eosinophils are related to a poor prognosis. (Davis 1994).
There are no BALF abnormalities that would be specific to sarcoidosis or alone diagnostic of this disease. A high percentage of lymphocytes (>30%) with predominating CD4 T-cells strongly suggests sarcoidosis whenever the clinical picture is compatible to sarcoidosis. Hypersensitivity pneumonitis involves typically lymphocytic alveolitis with a predominance of CD8 T-cells. (Davis 1994). The recent results have suggested that the CD4/CD8 T-lymphocyte ratio in the BALF of sarcoidosis patients is variable (Kantrow et al. 1997).
The proteins of serum constitute at least two thirds of the proteins in BAL fluid. Some of them are synthesised only outside the lungs, such as albumin, while some are produced both within and outside the lungs, such as immunoglobulins, and a few are produced only in the respiratory tract, such as surfactant. Many pulmonary diseases result in an increase of total proteins and other constituents derived from serum, which probably reflects the increased permeability associated with inflammation. In fibrosing alveolitis, total proteins, immunoglobulins and sometimes albumin are elevated in BALF. The increase of proteins of serum origin with high molecular weight suggests altered permeability. (Davis 1994).
Urea can be measured in BALF and can be used to estimate the amount of epithelial lining fluid (ELF). The original concentration of urea is the same in serum and in ELF, since the small molecular weight urea reaches complete equilibrium across the capillary-alveolar membrane. The ratio between BALF-urea and serum urea allows the calculation of the dilution of the original volume of ELF by BALF saline. This ratio can be used to calculate the individual constituents of ELF. (Rennard et al. 1986).
Various soluble constituents in BALF, including cytokines and other mediators of inflammation, collagen metabolism markers, fibronectin, ACE, etc, have been measured for scientific purposes, although none of them have yet reached the status of a standard diagnostic method.