Lung consolidation in a young-age active smoker: An unexpected diagnosis.

A 29-year-old man presented to Emergency Department with nonspecific symptoms. Through a series of radiological and invasive diagnostic studies we finally reach an unexpected diagnosis of hypersentivity pneumonitis; this is a complex and heterogeneous disease which diagnosis can be challenging as its clinical, radiologic and histopathologic features overlap with those of other interstitial lung diseases (ILDs). Diagnosing an ILD is a dynamic process, and that is the reason why complex cases discussed in a multidisciplinary team may need to be reconsidered in light of evolution of the disease and the results of the performed exams with a flexible approach.

Chemokine redundancy in BOS pathogenesis. A possible role also for the CC chemokines: MIP3-beta, MIP3-alpha, MDC and their specific receptors.

Bronchiolitis obliterans syndrome (BOS) is one of the most important factors limiting the long-term survival of lung transplant recipients (LTR), however its pathogenesis still remains unclear. We hypothesized that an increased production of certain specific proinflammatory mediators in the first post-transplant year would predispose to BOS. We retrospectively evaluated temporal kinetics of some CC chemokines that have not yet been evaluated, including CCL3/MIP1-alpha, CCL4/MIP1-beta, CCL17/TARC, CCL19/MIP3-beta, CCL20/MIP3-alpha, CCL22/MDC and CCL26/eotaxin, in broncho-alveolar lavage fluid (BAL-f) in the first post-transplant year in a cohort of 8 LTR before the development of BOS (pre-BOS LTR) and 8 LTR with long-term stable clinical conditions (stable LTR). Chemokine levels were assayed by means of a multiplex sandwich ELISA. Furthermore, for those ligands which resulted significantly predictive of BOS onset, we analyzed the expression of specific receptors (CCR) on BAL cells. The proportion of CCR-expressing BAL cells was assessed by flow cytometry. We demonstrated that MIP3-beta/CCL19, MIP3-alpha/CCL20, MDC/CCL22 levels at 6 months post-transplant significantly predicted BOS onset. In addition, the temporal behavior of these factors resulted significantly different in pre-BOS patients as compared to stable LTR. Finally the expression of CCR was documented on BAL lymphocytes and macrophages, and, in some cases, their expression was found to vary between the two groups. Within the complexity of the chemokine network, these three CCL factors could play an additive role in the pathogenesis of the inflammatory process leading to bronchiolar fibro-obliteration.

Peripheral CD4(+)CD25(+) TREG cell counts and the response to extracorporeal photopheresis in lung transplant recipients.

Extracorporeal photopheresis (ECP) has been proposed as a possible alternative therapy for patients with bronchiolitis obliterans syndrome (BOS), with some evidence of efficacy. Although the mechanism by which ECP exerts its protective effects remains to be determined, two recent studies suggest that the modulation of transplant immune rejection may depend on the capacity to increase the number of peripheral T-regulatory (Treg) cells. We evaluated the effect of ECP treatment on the number of naturally occurring CD4(+)CD25(+) Treg cells in the peripheral blood of six lung transplant recipients: in five cases after failure of augmented or changed immunosuppression for BOS, and in one case owing to persistent acute rejection in a patient who contracted chronic hepatitis C viral infection after lung transplant. A functional stabilization was observed in three of our five patients with BOS, which was accompanied by a slight increase or stabilization of the number of peripheral blood CD4(+)CD25(high) cells with in vitro features of Treg cells. On the contrary, two patients with BOS who did not experience graft functional stabilization also showed a decline in the peripheral Treg subset. In the last patient Treg cell kinetics showed stabilization during the first 5 months of ECP treatment when lung function remained stable and graft histology normalized but showed a subsequent decrease, predating BOS diagnosis. In all, our results indicate that ECP may modulate peripheral Treg cell number but the time course of peripheral Treg cells varies according to graft function.

Cutaneous vasculitis and reactive arthritis following respiratory infection due to Chlamydia pneumoniae: report of a case.

Unlike Chlamydia trachomatis and C. psittaci, the association of C. pneumoniae infection with immunological complications, such as reactive arthritis (ReA) or erythema nodosum (EN) has been rarely reported. Here we present the case history of a patient with C. pneumoniae community acquired pneumonia (CAP) who subsequently developed a ReA and a cutaneous vasculitis. A 45-year-old HLA B27 negative male developed an asymmetric and additive arthritis and a cutaneous leukocytoclastic vasculitis with IgM and complement papillary deposition along hypodermic vessel walls about three weeks after the onset of respiratory symptoms. The diagnosis of chronic Chlamydia pneumoniae infection was based on serology and PCR. Cultural and serological investigations for other infectious agents commonly involved in ReA were negative. This is the first report on the occurrence of two immune-based complications, associated to Chlamydia pneumoniae infection. Therefore, since this infection is very common in our population, although often asymptomatic, should be systematically considered as a common causative agent of ReA and of vasculitis.

Effects of continuous or pulsed exposure to rifabutin and sparfloxacin on the intracellular growth of Staphylococcus aureus and Mycobacterium tuberculosis.

The time-kinetics of the intracellular bioactivity and intracellular post-antibiotic effect (PAE) of rifabutin and sparfloxacin against Staphylococcus aureus and Mycobacterium tuberculosis, grown in human monocytes, were evaluated. Intracellular bactericidal activity against staphylococci was shown in the presence of extracellular drug concentrations equal or superior to 1/10 plasma Cmax. The bactericidal activity of rifabutin was dependent on both its extracellular concentrations and the exposure time. In contrast, the pattern of the intracellular activity of sparfloxacin was characterized by a minimal concentration dependent killing. Both antibiotics (from 1/10 to the expected lung Cmax) showed intracellular bioactivity against M. tuberculosis H37Ra and H37Rv strains. A long intracellular PAE on staphylococci (>4 hours) was demonstrated when drugs were removed from the infected monocytes after 1 h treatment. Our findings suggest that rifabutin and sparfloxacin may be useful in the treatment of lower respiratory tract infections due to intracellular pathogens.

A 10-year survey of Mycobacterium tuberculosis isolates in Pavia and their drug resistance: a comparison with other Italian reports.

A retrospective review was made of the bacteriological and medical records of patients with culture-confirmed pulmonary tuberculosis who attended the IRCCS San Matteo Polyclinic of Pavia, between 1990 and 2000. Altogether, 279 patients were included in the survey: 220 new cases and 59 prior treatment cases. Resistance to at least one drug, and resistance to both isoniazid and rifampicin (MDR) were more common among previously treated patients than among new cases (86.4% vs. 34.1%, and 44% vs. 5.9%, respectively). While the frequency of resistance to any drug showed no variation in the period examined, a trend toward a progressive decrease in the frequency of primary MDR-TB was observed (from 11.9% in 1990-1992 to 1.3% in 1998-2000). The level of resistance observed in our study suggests that all isolates of Mycobacterium tuberculosis should be tested for drug susceptibility, especially when obtained from patients who report a previous episode of the disease.

Monocyte chemoattractant protein-1 levels in bronchoalveolar lavage fluid of lung-transplanted patients treated with tacrolimus as rescue treatment for refractory acute rejection.

BACKGROUND: Cytokines are important mediators of the complex process of extravasation and influx of peripheral mononuclear cells into a site of graft injury, an action that may be affected by the immunosuppressive regimen. The aim of this study was to compare the effect of different immunosuppressive regimens on cytokine expression in the grafted lung. METHODS: We analyzed the cytokine profiles in broncho-alveolar lavage fluid (BAL-F) from 18 lung transplanted patients undergoing a shift from a cyclosporine- to a tacrolimus-based triple therapy regimen due to refractory acute rejection. RESULTS: Three months after the conversion to tacrolimus, BAL-F levels of interleukin 8 (IL8), IL18, IL12 and IL10 were not significantly different than those measured before conversion. In contrast, monocyte chemoattractant protein-1 (MCP-1) levels showed a significant and sustained decrease in BAL-F during tacrolimus therapy. In addition the levels of gamma interferon (IFN-gamma) in the BAL-F were decreased albeit not significantly. CONCLUSIONS: These findings suggest that the clinical and functional stabilization of patients observed after conversion to a tacrolimus based regimen, may be due, at least in part, to the induced down-regulation of MCP-1 production.

[Hepatitis C virus and mixed cryoglobulinemia in dialysis]. / Virus dell'epatite C e crioglobulinemia mista in dialisi.

Prevalence of hepatitis C virus (HCV) varies in the dialytic population according to the geographic area (5-85%); the European average is 19%, with marked differences between dialysis units. The means of virus transmission is still not clear and represents one of the major management problems faced by dialysis units. US authors and European study groups have recently demonstrated a high level od HCV infection in patients with essential mixed cryoglobulinemia (EMC), suggesting that the virus plays an etiological role. The authors examined the correlation between mixed cryoglobulinemia and HCV and the possible etiological role of the virus in the pool of patients undergoing dialysis at the Centre. In September 1994 28/63 (44.4%) patients were found to be Ab anti-HCV positive (second and third generation ELISA); circulating cryoglobulins identified as Type II following immunofixation were found in 2/28 patients (7%) using centrifugation and cold incubation techniques. In the absence of the pathologies classically associated with cryoglobulinemia, the patients were diagnoses as suffering EMC. The HCV/EMC correlation in the dialysed population has been analysed in a limited number of studies, with discrepant results (0-47%). This paper highlights the association between HCV and EMC in 7% of chronic dialysed patients and given that the finding of anti-HCV Ab in serum solely documents previous exposure to the virus, we can only indirectly attribute an etiological role to HCV. The search for viral RNA in the serum, cryocrit and surnatant of patients found affected by EMC may provide additional etiopathogenetic information.

Percutaneous computed tomography-guided radiofrequency thermal ablation of small unresectable lung tumours.

The aim of the current study was to evaluate the safety and the efficacy of radiofrequency thermal ablation (RFTA) for the treatment of nonsmall cell lung cancer (NSCLC) and isolated pulmonary metastases (METs) from colorectal cancer (CRC). A total of 31 patients (15 with NSCLCs and 16 with CRC lung METs), with 36 lung tumour nodules (mean+/-sd diameter: 22+/-8 mm, range: 10-35 mm) underwent computed tomography (CT)-guided RFTA using expandable electrodes. Contrast-enhanced CT was performed before and after (immediately and 30+/-5 days) each RFTA session to assess immediate results and complications and repeated 3 and 6 months post-RFTA, as well as every 6 months thereafter, to evaluate long-term results. Complete radiological necrosis was defined as a nonenhancing area at the tumour site that was equal to or larger than the treated tumour; persistence of enhancement at the tumour site indicated incomplete treatment. Local recurrence was defined as an increase in tumour size and/or enhancing tissue at the tumour site. Complete radiological necrosis of the 36 tumours was achieved with 39 RFTA sessions and 42 electrode insertions. No major complications or deaths were observed. Six patients experienced mild-to-moderate pain during the procedure. There were five cases of pneumothorax, none requiring drainage and four cases of pneumonia, which were successfully treated with antibiotics. After a mean follow-up of 11.4+/-7.7 months (range of 3-36 months), the overall local recurrence rate was 13.9% (20 and 9.5% for NSCLC and CRC-METs patients, respectively). Nineteen of the 31 (61.3%) patients were alive (15 apparently disease free) and 12 (38.7%) had died (three from causes unrelated to their cancer). Radiofrequency thermal ablation seems to be a safe, effective method for producing complete ablation of small nonsmall cell lung cancers and pulmonary colorectal cancer metastases.