Clinical Importance of Bronchoalveolar Lavage Fluid and Blood Cytokines, Surfactant Protein D, and Kerbs von Lungren 6 Antigen in Idiopathic Pulmonary Alveolar Proteinosis

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Abstract

OBJECTIVE:

To investigate the clinical importance of cytokines, surfactant protein D (SFTPD, formerly SP-D), and Kerbs von Lungren 6 antigen (KL-6) in bronchoalveolar lavage fluid (BALF) and blood in patients with idiopathic pulmonary alveolar proteinosis (iPAP).

PARTICIPANTS AND METHODS:

Patients with iPAP diagnosed by characteristic cytopathologic examination of BALF and pathologic examination of transbronchial lung biopsy specimens or open lung biopsy specimens were enrolled in the study from January 1, 1995, through June 30, 2005. To investigate the clinical importance of cytokines, SFTPD, and KL-6 in iPAP, we measured tumor necrosis factor superfamily, member 2 (TNF, formerly TNF-α) and interleukin (IL) 1β in BALF and IL-6, IL-10, IL-8, chemokine (C-C motif) ligand 4 (CCL4, formerly MIP-1β), chemokine (C-C motif) ligand 2 (CCL2, formerly MCP-1), SFTPD, and KL-6 in both BALF and blood in 15 patients with iPAP and 48 patients with interstitial lung diseases (diseased controls) (including 20 with interstitial pneumonitis associated with collagen vascular diseases, 13 with idiopathic pulmonary fibrosis, and 15 with sarcoidosis) and 20 individuals without pulmonary diseases (lung controls).

RESULTS:

Patients with iPAP had significantly higher levels of TNF. IL-6, IL-8, CCL4, CCL2, SFTPD, and KL-6 in BALF than did lung controls and had significantly higher levels of CCL4, CCL2, SFTPD, and KL-6 levels in BALF than did diseased controls. Patients with iPAP had significantly higher levels of IL-10, IL-8, CCL2, SFTPD, and KL-6 in blood than did lung controls and significantly higher levels of KL-6 in blood than did diseased controls. Levels of KL-6 both in BALF and blood were significantly correlated with serum lactate dehydrogenase level, arterial oxygen tension, and alveolar-arterial gradient in partial pressure of oxygen, the severity markers for iPAP, and were significantly higher in patients with iPAP who required subsequent therapeutic lung lavage.

CONCLUSION:

Patients with iPAP had elevated levels of SFTPD, KL-6, and cytokines in both BALF and blood. Elevated levels of KL-6 in both BALF and blood may be valuable in reflecting disease severity of patients with iPAP and in determining the need for therapeutic lung lavage.

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