Serum Type III Procollagen Peptide in Patients withPneumocystis cariniiInfection

Abstract

Inflammation may play a central role in the pathogenesis of HIV-related Pneumocystis carinii pneumonia (PCP). Serum levels of the amino-terminal propeptide of Type III procollagen (PIIINP) reflect inflammatory activity in granulation tissue and in chronic rheumatic and liver disorders. To investigate changes in PIIINP serum levels during an episode of HIV-related PCP, consecutive serum samples were taken from 48 HIV-infected patients with PCP in a randomized, placebo-controlled study of the effect of adjunctive methylprednisolone therapy (26 in corticosteroid [CS] group and 22 in control group). All patients were treated with co-trimoxazole. In the control group, PIIINP serum levels at day of initiation of therapy (Day 0) were significantly higher in patients requiring mechanical ventilation and/or dying during the course of the pneumonia, and serum levels of PIIINP higher than 5 ng/ml were associated with a higher mortality than levels below 5 ng/ml. The level of PIIINP increased from Day 0 to Day 5. There was a significant correlation between changes in PIIINP levels and changes in the alveolar-arterial oxygen gradient from Day 0 to Day 5. In the CS group, the PIIINP levels decreased while steroid was administered. At Days 21 to 28 there were no difference in the levels of PIIINP between the two groups. PIIINP serum levels may predict the clinical outcome of PCP. The antimicrobial therapy may exacerbate the inflammatory reaction in HIV-related PCP, leading to respiratory failure. CS prevents this increased inflammatory activity.

Circulating Collagen Biomarkers as Indicators of Disease Severity in Pulmonary Arterial Hypertension

“…Published research showed that in hypertensive heart failure patients with elevated cardiac filling pressures, an increase in circulating TIMP-1 levels relative to MMP1 levels suggested ongoing collagen synthesis (11). Several studies have shown that cardiac fibrosis histology measures are associated with circulating fibrosis biomarkers (12,13). These and other data established that excessive collagen metabolism due to progressive vascular remodeling plays a distinct role in the pathophysiology of PAH and that collagen content of a tissue may be assessed with the serum analysis of breakdown products of collagen.…”

“…Studies show that the transpulmonary gradient of procollagen III occur in normal subjects undergoing cardiac catheterization suggesting that normal human lungs can actively synthesize collagen (9). It has been established that elevated procollagen III levels in the serum mirror changes in bronchoalveolar lavage of patients with sarcoidosis (10), interstitial pulmonary fibrosis (11), pneumocystis carinii pneumonia (12), acute lung injury (13), and acute respiratory distress syndrome (14,15) indicating that such parenchymal changes are reflected in peripheral blood samples. These studies suggest that ongoing collagen metabolism in the pulmonary vascular can be assessed by measuring circulating levels of collagen metabolites.…”

Procollagen Types I and III Aminoterminal Propeptide Levels during Acute Respiratory Distress Syndrome and in Response to Methylprednisolone Treatment

“…The significant correlation detected during therapy among these variables indicates a likely casual link between reduction in fibrogenesis and resolution of pulmonary and extrapulmonary organ dysfunction. Two prior clinical reports have described a reduction in circulatory PIIINP levels during prolonged glucocorticoid treatment of patients with usual interstitial pneumonitis (16), and pneumocystis pneumonia (44). Both studies found that a reduction in circulatory peptide levels correlated with improvement in lung physiology (16,44).…”

XVI. ThePneumocystis cariniimajor surface glycoprotein (MSG): its potential involvement in the pathophysiology of pneumocystosis

“…Adjuvant corticosteroid therapy has reduced the overall mortality rate among moderately severe cases by 40%[41]. Several markers of disease severity are associated with outcome, including arterial oxygenation, serum lactate dehydrogenase, BAL neutrophilia, BAL IL‐8, and PIIINP (a marker of activation and overall inflammation) [42–48].…”