Objective The goal of this study was to determine if biomarkers of collagen metabolism in pulmonary arterial hypertension (PAH) identify patients with worse disease and higher risk of death. Background The relationship between markers of collagen metabolism, degree of disease, and outcome in PAH is unknown. Methods Stable idiopathic, anorexigen-associated and hereditary PAH patients were prospectively enrolled. Collagen biomarkers levels were measured: N-terminal propeptide of type III procollagen (PIIINP), C-terminal telopeptide of collagen type I (CITP), matrix metalloproteinsase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1). Patients were divided into mild, moderate, and severe PAH groups. Data was compared between tertiles of each biomarker. Pearson correlation and Spearman rank coefficient analyses were performed. Data on time to death or transplantation was examined by Kaplan-Meier survival curves. Results Circulating levels of PIIINP, CITP, MMP9 and TIMP1 were higher in the PAH group (N=68) as compared to age- and gender-matched healthy controls (N=37) (p<0.001 for each). PIIINP levels increased with the severity of disease (p=0.004). PIIINP tertile data indicated that with increasing levels, six-minute walk distance (6MWD) and cardiac index (CI) decreased and WHO FC worsened, and resting heart rate increased. A significant correlation existed between PIIINP with worsening WHO FC (rs=0.319, p=0.008) and a negative correlation with CI and 6MWD (r=-0.304 and -0.361 respectively; p<0.05). PIIINP tertiles showed a trend towards worse outcome in patients with higher tertile (lung transplant or death) (p=0.07, log rank test). Conclusions Markers of collagen metabolism were associated with worse disease in PAH patients.

Immunocompromised patients are susceptible to many pathogens, including those that are predominantly problems in veterinary medicine. We report a case of a 42-yr-old white male who presented 19 months post-cadaveric renal transplant (for IgA nephropathy) with a 5 d history of nausea, vomiting, abdominal cramping and diarrhea. Admission chest X-ray revealed a suspicious mass lesion in the left lower lobe. Computed tomography (CT) guided biopsy of the lesion showed a large zone of CD68 +ve histiocytes in a non-caseating granuloma. Gram stain revealed multiple gram-positive rods within the histiocytes, which were eventually identified as R. equi. After 4 months of therapy with fluoroquinolones (Avelox) and Azithromycin a repeat CT showed complete resolution of the lesion. We reviewed the literature with special focus on the clinical features, challenges in diagnosis, and treatment of this rare infection (especially in the transplant patients who are also on immunosuppressive therapy).

The renin–angiotensin–aldosterone system is implicated in the pathophysiology of pulmonary arterial hypertension. We undertook this study to determine the effects of spironolactone, a mineralocorticoid receptor blocker, on collagen metabolism in pulmonary arterial hypertension patients. After obtaining institutional review board approval and informed consent, 42 pulmonary arterial hypertension patients were prospectively enrolled and 35 patients completed the 16-week randomized double-blinded crossover clinical trial. Subjects received 50 mg spironolactone or placebo and at the end of week 8, treatment arm was switched. Circulating levels of collagen biomarkers, brain natriuretic peptide, and aldosterone levels were measured, and six-minute walk distance, liver function tests, and echocardiogram data were collected at weeks 0, 8, and 16. Mean age was 45 ± 15 years and 87% were females. At baseline, brain natriuretic peptide and aldosterone levels were 74 ± 95 pg/ml and 7 ± 8 pg/ml, respectively. There was no change in the levels of amino-terminal propeptide of procollagen type III (PIIINP), MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio at weeks 8 and 16 compared to baseline values in placebo arm and treatment arm. The baseline six-min walk distance was 436 ± 115 meters at baseline and no change in walk distance was noted at weeks 8 and 16 ( P = 0.372). None of the patients developed hyperkalemia or liver function test abnormalities at weeks 8 and 16 requiring discontinuation of study drug. Our study showed no change in collagen metabolite levels in pulmonary arterial hypertension patients treated with spironolactone. Spironolactone was safe and well tolerated by pulmonary arterial hypertension patients with no increased hyperkalemia or liver function test abnormalities.

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