Bronchiolitis obliterans-organizing pneumonia: an Italian experience.

The purpose of this study was to describe the clinical features at onset and outcome and the diagnostic approach in subjects with bronchiolitis obliterans-organizing pneumonia (BOOP). Over a 7-year period we observed 78 cases of biopsy-proven bronchiolitis obliterans-organizing pneumonia, in which well documented clinical and radiographic data were available. The final diagnosis of BOOP was validated when patients presented: (i) negative microbiological analysis on BAL fluid; (ii) a well documented improvement either spontaneous, or after steroid treatment or (iii) cases with progressive respiratory failure and increasing radiographic shadows, an open lung biopsy or autopsy that excluded other entities. There were 42 males and 36 females; the mean age was 61+/-12 years (range 12-85 years). Forty-two (54%) patients were current smokers, 25 (32%) had never smoked and 11 (14%) were ex-smokers. The clinical pattern at presentation of BOOP was more frequently similar to classical acute or sub-acute infectious pneumonia. Fever (63%), dyspnoea (58%) and dry cough (53%) were the typical symptoms on admission. A flu-like syndrome preceeding BOOP was observed in 21 cases (27%). Inspiratory crackles (78%) were the most typical finding at physical examination. However, 13% of the patients were asymptomatic and an abnormal chest X-ray film was the reason for seeking medical attention. Radiographically the most frequent pattern of BOOP was a unilateral consolidation (44%) with lower field predominance. A migratory behaviour was present in 22% of the cases. High-resolution computed tomographic (HR-CT) scan when performed, was more sensitive in detecting ground glass infiltrates, sub-pleural or peri-bronchovascular distribution or the presence of nodules or cavitation. Most patients (68%) were classified as having idiopathic BOOP. However, the same clinical-roentgenological pattern was observed in patients after radiotherapy for ductal breast carcinoma (6%), in collagen-vascular diseases (6%), related to drugs (9%), to infections serologically documented (4%), and to graft vs. host disease (4%). Four patients (all of whom had idiopathic BOOP) presented a rapid progressive respiratory failure needing mechanical ventilation. In another two cases respiratory failure appeared after a long period during which patients experienced exertional dyspnoea and low grade fever. BAL profile was characterized by lymphocytosis with a reduction of the CD4/CD8 ratio, associated with a slight increase of neutrophils and eosinophils and scattered mast cells. However in two cases we had an increased CD4/CD8 ratio and in one case the presence of a significant 12% of polyclonal B cells. In a few cases atypical (cytokeratin-positive cells) epithelial cells were detected: these cells were constantly present in the BAL fluid of patients with rapidly progressive respiratory failure. From the diagnostic point of view this series documents that transbronchial lung biopsy (coupled with BAL) can be the first diagnostic step. However, therapy can be started on the basis of BAL data (when a characteristic morphological and phenotypical profile is evident) in cases in which the clinical presentation is suggestive and a biopsy cannot be made. Most patients showed a rapid and good response to steroid therapy. However, three patients died (4%) in spite of steroid therapy (two cases) and steroid and cyclophosphamide therapy (one case). In conclusion, although clinical findings, chest X-ray film and CT Scan findings usually suggest the diagnosis a definite confirmation requires transbronchial lung biopsy and BAL and, less frequently, open lung biopsy.

The diagnostic value of bronchoalveolar lavage and transbronchial lung biopsy in cryptogenic organizing pneumonia.

In order to determine the diagnostic value of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) in cryptogenic organizing pneumonia (COP) a prospective study was carried out. Thirty seven consecutive patients (20 males and 17 females) with clinicoradiological features of COP were enrolled in the study. The statistical analyses were completed in 35 cases. Twenty eight patients were diagnosed to have COP, all of them with a confirmatory biopsy. In seven cases, a different diagnosis was made. BAL cytological and phenotypical criteria considered for the diagnosis of COP were: a lymphocytosis of more than 25% (with a CD4/CD8 ratio less than 0.9); combined with at least two of the following data (foamy macrophages of > 20%, and/or neutrophils of > 5%, and/or eosinophils of > 2% and < 25%). TBLB specimens were classified as positive for COP if they showed: buds of granulation tissue within the centrilobular air spaces; infiltration of alveolar walls with chronic inflammatory cells; and preservation of alveolar architecture. BAL was performed in 34 patients; 17 cases were consistent with the final diagnosis of COP (sensitivity 63%), and four cases were correctly classified as negative (specificity 57%). BAL had a positive predictive value (PPV) of 85% and a negative predictive value (NPV) of 29%. TBLB was performed in 32 patients; it correctly identified COP in 16 cases (sensitivity 64%), and six cases were correctly classified as negative (specificity 86%). TBLB had a PPV of 94% and a NPV of 40%. The accuracy of the examinations, that is the probability of correctly diagnosing both diseased and nondiseased patients by BAL or TBLB, was 62 and 69%, respectively. Our findings suggest that the combination of cytological bronchoalveolar lavage and histological transbronchial lung biopsy data obtained during a fibreoptic procedure appears to be an effective method for the initial investigation in cryptogenic organizing patients pneumonia presenting with patchy radiographic shadows.

Preliminary results in HIV-1-infected patients treated with transfer factor (TF) and zidovudine (ZDV).

The efficiency of HIV-1 specific transfer factor (TF) administration, combined with Zidovudine (ZDV), in asymptomatic persistent generalised lymphadenopaty, or AIDS related complex (ARC) patients was evaluated. Twenty patients were randomly assigned to receive only ZDV (1st group) or ZDV together with HIV-1-specific TF (2nd group). HIV-1-specific TF was administered orally at 2 x 10(7) cell equivalent daily for 15 days, and thereafter once a week for up to 6 months. There were no significant differences between the two groups in clinical evolution, red blood cells, haemoglobin, lymphocytes, CD20 subset, transaminases, beta-2-microglobulin, p24 antigen. White blood cells, CD8 lymphocytes as well as IL-2 levels increased in the second group, while the CD4 subset increased in the first group. The combination treatment with ZDV and TF appeared to be safe and well tolerated. Furthermore, levels of serum cytokines were investigated in 10 patients (8 asymptomatic and 2 ARC) treated with ZDV, and compared with 5 patients of the 2nd group (3 asymptomatic and 2 ARC) treated with ZDV plus HIV-1-specific TF. Peripheral lymphocytes, CD4, CD8 subsets, IL-2, TNF alpha, IL-6, p24 antigen, IL-2 soluble lymphocyte receptors (sR), CD4sR, CD8sR and beta-2-microglobulin were evaluated at the baseline and at the 3rd month. The CD4 subset was not significantly different in the two groups, whilst IL-2 increased in the 2nd group receiving ZDV plus TF, suggesting an activation of the Th1 secretion pattern.

[Changes in the cell-mediated immune system in post-traumatic sepsis]. / Alterazioni del sistema immunitario cellulo-mediato nella sepsi post-traumatica.

OBJECTIVE: We studied the alterations of cell-mediated immunity (CMI) in polytrauma patients and its relation with sepsis. DESIGN: a prospective study. SETTING: ICU, Ospedale Maggiore, Bologna (Italy). PATIENTS: We included in the study 42 patients with at least two of following criteria: 1) Trauma Score < or = 12; 2) Abbreviated Injury Score > or = 4; 3) Arterial Pressure on admission < or = 80 mmHg; 4) Injury Severity Score > or = 16. CMI examinations were carried out at three different post-traumatic times (T0-T2). Seventeen patients developed a sepsis within the first eight days from admission. RESULTS: Sepsis caused a temporary impairment in some lymphocyte subsets at T2. The patients who developed sepsis showed a significant subset percentage difference for CD3, CD3 activated (p < 0.05) and for interleukin-2 receptor (IL-2R) (p < 0.01) in comparison with the non septic group. At T2, the seven septic patients who died, showed a marked depression of IL-2 values (0.37 +/- 0.12 UI/ml) in comparison with the values of septic patients who survived (0.66 +/- 0.25 UI/ml; p < 0.01) and with the group of non septic patients (0.83 +/- 0.5 UI/ml; p < 0.001). Septic patients who had a IL-2 value of 0.45 or lower had a mortality of 75%. IL-2 values showed a specificity of 89% and a sensibility of 75% in predicting mortality in septic trauma patients. CONCLUSION: We believe that in polytrauma patients IL-2 values monitoring could be a reliable index of the disfunction of CMI and that IL-2R sieric levels could be a diagnostic marker of impending sepsis.

[Zinc and lymphocyte subsets in patients with HIV infection]. / Zinco e assetto linfocitario in pazienti con infezione da HIV.

Serum zinc levels were assayed in patients with AIDS and related syndromes, using spectrophotometry and atomic absorption. Statistical data have shown that serum zinc levels, in addition to being significantly lower (p less than 0.001) among different groups and controls, decrease progressively with the worsening of the clinical and immunological picture from LAS to AIDS. Serum zinc levels in patients with AIDS and ARC have, moreover, been demonstrated to be related (r = 0.8240; p less than 0.001) to the lymphocyte subset CD4 helper-induced. These results suggest that serum zinc determination and possibly zinc therapy might be reasonably considered in the management of patients with symptoms of HIV infection.

Serum protease inhibitors in acute viral hepatitis.

Serum levels of alpha 1-antitrypsin (alpha 1-AT) and alpha 2-macroglobulin (alpha 2-M) and, as controls, alpha 1-acid glycoprotein (alpha 1-AG) and haptoglobin were evaluated by means of laser nephelometry in 17 patients with acute viral hepatitis (AVH) type A, 16 with AVH-B, 12 with AVH-NANB and 8 with fulminant hepatitis B. On admission, alpha 1-AT levels were elevated in one third of AVH-A and AVH-B cases, but subsequently declined; alpha 2-M levels were elevated in about 40% of AVH-B patients during the 2nd, 3rd and 4th week after admission. No significant correlation was found between elevated levels of protease inhibitors and aminotransferase values or drug addiction and delta coinfection. alpha 1-acid glycoprotein and haptoglobin levels were always normal or low. Protease inhibitors did not show any elevation in fulminant hepatitis, while changes were found only in a few patients with AVH-NANB. Thus, no clearcut pattern of changes in protease inhibitors has been found in association with each type of hepatitis, although alpha 1-AT and alpha 2-M elevations are mainly found in AVH-B.

A clinical-immunological evaluation of AIDS cases and related syndromes.

The clinical features of our cases demonstrated some of the already known characteristics of the variable spectrum of HIV infection. DA are the most important risk category in Italy. 10% of the ARC cases evolved into AIDS during a 12-month follow-up, on average. The most frequent OI in our AIDS cases were PCP, C. albicans esophagitis and chronic mucocutaneous ulcers. An high percentage of neurologic involvement from HIV was observed, and malignancies were encountered in AIDS (3 KS and 1 undifferentiated B lymphoma) as well as in ARC (1 Hodgkin's lymphoma). Statistically, significant worsening of the immunologic situation is evident as the disease progresses from LAS to AIDS. Activated B lymphocytes represent most of the cells of the germinal center during the hyperplastic stage of lymphadenopathy. Reversal of the T4/T8 ratio appears early during the initial stage of lymphadenopathy and is due to a decrease of CD4 and a relative increase of CD8. Also, destruction of the follicular dendritic cells is an early feature which becomes more evident as the disease advances and the lymph node evolves toward progressive involution. Activated B-lymphocyte augmentation with polyclonal Ig secretion appears to be related to T-independent B stimulation by coinfection such as CMV, EBV and HBV. The increase of cytotoxic/suppressor lymphocytes seems to be partly related to the excessive activation of B lymphocytes and partially directed to the cells infected by HIV or coated with its proteins (6,7,8,9). The destruction of follicular dendritic cells has been interpreted not only as a killer effect of the virus but also as a result of the intervention of CTL sensitized to the cells containing the virus (10,11). Their destruction may contribute to the impaired recognition of soluble antigen which is one of the main features of the immune deficiency of HIV infection (9,13,16).

[Nosology of contraceptives: hematological and ultrastructural observations after experimental administration of low dosage contraceptives (author's transl)]. / Nosografismo iatrogeno da contraccettivi: rilievi ematochimici ed ultrastrutturali dopo somministrazione sperimentale di estroprogestinici a basso dosaggio.

A further experimental study on changes produced in rabbits by low dosage contraceptives is presented. The administration has been continued for six months. Serum biochemical and hepatic ultrastructural findings are in agreements with literature data. On the contrary the early changes of cardiac microcirculation and chiefly renal glomerular tuft seem to be rather unusual. The weight to be attached to the knowledges descending from the presented data in assessing allowance of contraceptive treatments in human subjects and aiming preventive medicine purposes is emphasized.