Elsevier

Mayo Clinic Proceedings

Volume 83, Issue 12, December 2008, Pages 1344-1349
Mayo Clinic Proceedings

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

https://doi.org/10.4065/83.12.1344Get rights and content

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.

Section snippets

PARTICIPANTS AND METHODS

The Taipei Veterans General Hospital Institutional Review Board approved this prospective study, and informed consent was obtained from all study participants. Fifteen consecutive patients (10 men [67%], 5 women [33%]) with iPAP diagnosed by characteristic cytopathologic examination of BALF16 and pathologic examination of transbronchial lung biopsy specimens or open lung biopsy specimens were enrolled during a period of 10 years (from January 1, 1995, through June 30, 2005). All patients with

Clinical Data

The demographic data, including sex and smoking habits, showed no substantial difference between patients with iPAP and any subgroup of the diseased controls and lung controls. Patients with iPAP were slightly younger than lung controls (mean ± SD age, 40.6±14.6 vs 52.4±20.4 years; P=.06) and significantly younger than those with ILD (interstitial pneumonitis associated with collagen vascular diseases, 62.6±13.2 years, P<.001; IPF, 68.9±9.2 years, P<.001; sarcoidosis, 53.2±14.4 years, P=.03).

DISCUSSION

To our knowledge, ours is the first single-center study to investigate the clinical importance of BALF and blood levels of SFTPD, KL-6, and various cytokines. Elevated serum and/or BALF levels of SFTPD and KL-6 are reported in patients with iPAP12, 13, 14 and are useful in helping to diagnose iPAP, estimate its disease activity, and monitor for the treatment response of GM-CSF therapy.12, 13, 14, 15

In agreement with previous studies, we found that BALF levels of SFTPD and KL-6 were

CONCLUSION

Lungs of patients with iPAP may be prototypical of chronic inflammation, as evidenced by elevated levels of chemokines and proinflammatory cytokines, SFTPD, and KL-6 in BALF. Furthermore, levels of KL-6 in BALF and blood may serve as a disease severity marker for iPAP and an aid in determining the need for subsequent therapeutic lung lavage.

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    This work was supported by grants NSC 94-2314-B-075-097 and NSC 95-2314-B-010-026 from the National Science Council of the Republic of China. The study sponsors were not involved in the study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or the decision to submit the manuscript for publication.

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