Lymphangiogenesis as a prerequisite in the pathogenesis of lung fibrosis.

Despite increasing knowledge on the cellular and molecular mechanisms involved in pulmonary fibrosis, its therapeutic options are still limited. The study of lymphangiogenesis has contributed to a better understanding of tumor growth and metastasis, with a major impact upon changes in therapeutic strategies and this was followed by the research of lymphatic vessels in other pathological conditions. Some data support the possible role of lymphangiogenesis in the pathogenesis of lung fibrosis. However, at the time of diagnosis for each patient with a fibrotic interstitial lung disease, it is necessary to predict the prognosis and to choose for individual targeted-therapy. Our aim was the characterization of lymphangiogenesis as a useful tool to stratify patients with lung fibrosis. We evaluated the presence, morphology and density of D2-40-positive lymphatic vessels and co-localization of D2-40/Ki67 in pulmonary fibrosis with different degrees of severity and without a specific etiology. Lymphatic vessel density did not correlate with severity grade and ranged between 4.66 to 38.33 vessels/×40 field, with the highest value in degree III of fibrosis. An intense proliferative activity of lymphatic endothelial cells was found in 24% (6 out of 25) of cases. The morphology of lymphatics and the presence of splitting combined with the proliferative activity of endothelial cell pillars suggested two different mechanisms in the formation new lymphatic vessels. Our results support the hypothesis that the activity and ongoing evolution of fibrosis can be predicted through the characterization of lymphangiogenesis but its presence or absence cannot predict the severity of fibrosis.

From basic lesions to a pathological staging of pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a severe disease, with unpredictable evolution that frequently leads to respiratory failure and death, despite some progresses made in the field of therapy. Basically, the bad prognosis and failure of therapy are the consequence of the lack of data about the molecular events that have as result the extensive fibrosis. Although the basic lesions were defined many years ago, the pathological classification of pulmonary fibrosis is controversial. In the present work, we analyzed the prognostic impact of basic microscopic lesions on a possible new classification that could be related to the patient outcome. For this purpose, we have investigated 20 cases with idiopathic pulmonary fibrosis and samples of lung parenchyma were obtained by video assisted thoracoscopy. The specimens were processed by usual histological technique and sections were stained with Hematoxylin-Eosin, Masson's trichrome and Gordon-Sweet silver staining. There were evaluated the lung architecture, the chronic inflammatory infiltrate, macrophages and fibrosis. The distribution and severity of each parameter was converted into points and finally graded from I to IV, with corresponding score from 1 to 12. We found four cases with degree II, 12 with degree III, and four with degree IV. Our results support the hypothesis that the evaluation of basic lesions could be the basis for a more objective classification and staging of lung fibrosis and, possibly, a better prognostic method and, eventually, a predictor for the response to targeted therapy.

Tuberculosis infection versus anti-tumor necrosis factor therapy: screening challenges in psoriatic patients.

OBJECTIVES: The aim of this study was to analyze the performance of the tuberculin skin test (TST) for screening and monitoring patients treated with anti-tumor necrosis factor agents, in a high-incidence area. METHODS: A 3-year retrospective study was carried out on 268 subjects. The study included 68 patients with moderate-to-severe psoriasis, screened for latent tuberculosis infection (LTBI) and subjects without psoriasis (100 adults and 100 children) with close contact with infected individuals. RESULTS: Positive tuberculin skin test (TST) results (induration >5 mm) were observed in 70.5% (48/68) of patients with psoriasis, higher than those observed in subjects with suspicion of tuberculosis or with close contact with infected individuals: 51% (51/100) in the adult group and 30% (30/100) in the children group. CONCLUSIONS: These results show that the prevalence of LTBI evaluated with the TST in the psoriatic group is higher than in subjects without psoriasis. LIMITATION: The positive reactions were not confirmed by other verification methods.