Objectives: To assess the diagnostic value of bronchoalveolar lavage fluid (BALF) ferritin as a lung tumor marker by comparing serum and BALF ferritin concentrations in patients with peripheral lung cancer versus control subjects with benign lung disease, and to examine the theory of ferritin compartmentalization around the tumor area by comparing ferritin concentrations in serum and bilateral (affected and unaffected side) BALF in cancer patients. Methods: Four groups of patients were investigated: 10 control nonsmokers, 10 control smokers, 10 smokers with chronic obstructive pulmonary disease (COPD), and 22 patients with primary bronchogenic carcinoma. A bronchoalveolar lavage (BAL) was performed in all subjects (both sides in 13 oncological patients, one side in the others) and samples of BALF and blood were submitted to biochemical analysis. Results: As a lung tumor marker, BALF ferritin showed 54% sensitivity and 93% specificity and serum ferritin 22% sensitivity and 93% specificity. A significant difference was observed between the two sides in the cancer patients (p = 0.033), and between BALF ferritin from the affected side and COPD patients (p = 0.025). Greater differences were obtained when BALF ferritin in the affected side of cancer patients was compared with values in both control nonsmokers (p < 0.0001) and control smokers (p < 0.001). Conclusions: These findings seem to confirm the relative diagnostic value of BALF ferritin as a lung tumor marker and the theory of ferritin compartmentalization. However, further studies are required to clarify the relations between iron and ferritin on the one hand and inflammation, tumorigenesis and host response on the other.

TDP-43 cellular levels are tightly regulated, increases, or decreases in these have deleterious effects in cells. The predominant mechanism responsible for regulation of the TDP-43 levels is an autoregulatory negative feedback loop. In this study, we identified an in vivo cause/effect relationship between TARDBP gene promoter methylation and specific histone modification and the TDP-43 levels in tissues of mice at two different ages. Furthermore, epigenetic control was observed in mouse and human cultured cell lines. In amyotrophic lateral sclerosis, the formation of TDP-43-containing brain inclusions removes functional protein from the system. This phenomenon is continuous but compensated by newly synthesized protein. The balance between sequestration and new synthesis might become critical with ageing, if accompanied by an epigenetic modification-regulated decrease in newly synthesized TDP-43. Sequestration by aggregates would then decrease the amount of functional TDP-43 to levels lower than those needed by the cell and thereby triggers the onset of symptoms.

In order to determine whether the alterations of immunoregulatory T cells described both in smokers and in patients with lung cancer occur in the deep lung as well as in peripheral blood, we analyzed T lymphocyte subpopulations in bronchoalveolar lavage (BAL) and in the blood of 12 patients with untreated lung cancer and of 8 controls. The immunocompetent cellular population of BAL fluid analyzed by differential cell count of alveolar macrophages, lymphocytes and neutrophils did not show considerable differences in the two groups studied. By contrast, the analysis of BAL T lymphocytes and their subsets showed significant alterations in patients compared with controls: a percentage increase of OKT3⁺ and OKT8⁺ lymphocytes and a decrease of the OKT4⁺/OKT8⁺ ratio was found in both the involved and uninvolved lung of patients. The immunologic pattern of T lymphocytes in blood did not show significant differences between patients and controls. Our data indicate that alterations in immunoregulatory T cells in lung cancer are more pronounced in BAL fluid obtained from both lungs than in peripheral blood.

In order to confirm the usefulness of free plasma DNA detection in the diagnosis of pulmonary embolism (PE), we have studied 16 patients with PE, 33 with various diseases, and 13 normal subjects. Free plasma DNA was detectable in 15 of 16 patients with PE (94%) and in 3 control patients, but never in plasma from normal subjects. In most cases, DNA was detectable until the 10th day after PE. In conclusion, counterimmunoelectrophoresis is a rapid, inexpensive and specific test which may be used as an exclusion test in the detection of patients suspected of having PE, who will have to undergo more extensive evaluation.

Abnormal autonomic nervous system responsiveness may contribute to the pathogenesis of allergic diseases. Therefore, we measured the beta-adrenergic systemic (metabolic) responsiveness by means of acute potassium load in 10 normal healthy subjects and in 19 patients with allergic asthma and/or rhinitis. Ten allergic patients showed a greater potassium increment, as in normal subjects, when potassium was infused in the presence of propranolol. There was no difference between asthmatic and rhinitic patients. We then examined the relation between the response to potassium tolerance and the nonspecific, nonpharmacological bronchial reactivity in response to inhalation of ultrasonically nebulized distilled water. Some allergic patients showed bronchial hyperreactivity, while others did not show a difference compared with the controls; there was no significant difference between asthmatics and rhinitics, and there was no relation between nonspecific bronchial reactivity and potassium load tolerance. These findings suggest that systemic beta-adrenergic hyporesponsiveness may be present only in some allergic patients. There is no demonstrable relation among atopic state, nonspecific, nonpharmacological bronchial reactivity, and systemic beta-adrenergic hyporesponsiveness.