Background: The pathological diagnosis of interstitial lung diseases (ILD) by surgical lung biopsy is important for clinical decision making. There is a need, however, to use serum markers for differentiating usual interstitial pneumonia (UIP) from other ILD. Surfactant protein (SP)-A, SP-D, KL-6, sialyl SSEA-1 (SLX), and sialyl Lewis a (CA19-9) are useful markers for the diagnosis and evaluation of activity of ILD. We have investigated the usefulness of these proteins as markers of UIP. Methods: Serum and bronchoalveolar lavage (BAL) fluid levels of the above five markers were measured in 57 patients with various forms of ILD (19 with UIP, 12 with non-specific interstitial pneumonia (NSIP), eight with bronchiolitis obliterans organising pneumonia (BOOP), and 10 with sarcoidosis), eight patients with the control disease (diffuse panbronchiolitis (DPB)), and nine healthy volunteers. Results: Serum levels of SP-A, SP-D, and KL-6 in patients with UIP and NSIP were significantly higher than in healthy volunteers. In particular, the serum levels of SP-A in patients with UIP were significantly higher than in patients with NSIP (p<0.0001, mean difference -58.3 ng/ml, 95% confidence interval -81.6 to -35.0), and BAL fluid levels of SP-D in patients with UIP were significantly lower than in patients with NSIP (p=0.01, mean difference 322.4 ng/ml, 95% confidence interval 79.3 to 565.5). Conclusion: Serum SP-A levels may be clinically useful as a biomarker to differentiate between UIP and NSIP.

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Diffuse panbronchiolitis (DPB) can now be cured with long-term erythromycin treatment. Our group conducted a prospective open trial of long-term treatment with a macrolide antibiotic, clarithromycin. We studied ten patients who were treated for 4 years with oral clarithromycin (200 mg once a day). Pulmonary function test, blood gas analysis, comprehensive improvement score, and bacterial culture of sputum were examined at 3, 6, 12 months, and at 2, 3, 4 years after the initiation of the therapy. Pulmonary function improved in most of the patients within 6 months: the forced expiratory volume in one second showed a maximal increase from a mean (SE) value of 1.74 (0.12) l at baseline to 2.31 (0.22) l at 6 months (P < 0.01) and the volume (l) of forced vital capacity also showed a maximal increase within 6 months. The partial pressure of arterial oxygen at rest significantly increased at 3-6 months. The comprehensive improvement score also reached maximum within 6 months in nine of the patients. The majority of patients have developed sputum culture in which bacteria were negative within 6 months after the therapy. All of the patients maintained a stable condition with continued therapy, and no side effects of clarithromycin were observed during the study. This prospective study demonstrated that 6-month treatment with clarithromycin might be necessary to improve the clinical conditions of patients with DPB and the drug could be safely used for a long term.

Diffuse panbronchiolitis (DPB) is a chronic lower respiratory tract infection commonly associated with persistent late-stage Pseudomonas aeruginosa infection. However, low-dose long-term therapy with certain macrolides is effective in most patients with DPB. The present study was designed to examine the effects of long-term erythromycin (ERY) therapy by using our established murine model of chronic respiratory P. aeruginosa infection. ERY or saline was administered from day 80 after intubation with a P. aeruginosaprecoated tube for the subsequent 10, 20, 40, and 80 days. Bacteriologic and histologic analyses of the murine lungs and electron microscopy of the intubated tube were performed. In the murine model, treatment with ERY for 80 days significantly reduced the number of viable P. aeruginosa organisms in the lungs (P < 0.05). The biofilm formed in situ by P. aeruginosa on the inner wall of the inoculation tube placed into the murine bronchus became significantly thinner after 80 days of ERY treatment. We conclude that the clinical efficacy of macrolides in DPB may be due at least in part to the reduction in P. aeruginosa biofilm formation.

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