We evaluated the performance of procalcitonin (PCT) and C-reactive protein (CRP) threshold values and kinetics as predictors of ventilator-associated pneumonia (VAP) survival and septic shock development.45 adult patients with VAP were studied. Serum CRP and PCT levels and the Sequential Organ Failure Assessment (SOFA) score were measured on days 1, 4 and 7 (D1, D4, D7) of VAP and their variations between different days (kinetics) were calculated (DPCT, DCRP). A multivariate logistic regression model was constructed with either VAP 28-day survival or septic shock development as dependent variables, and PCT values, CRP values, kinetics, age, sex, SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) II score as independent variables.No difference was found in CRP levels between survivors and nonsurvivors. Nonsurvivors had significantly higher PCT levels on D1 and D7. In the multivariate analysis, the only factors predicting VAP survival were DPCT 7-1 (OR 7.23, 95% CI 0.008-0.468) and DCRP 7-4 (OR 4.59, 95% CI 0.013-0.824). VAP patients who developed septic shock had significantly higher CRP levels on D1 and D7 and higher PCT levels on D1 and D4. The only factor predicting the development of septic shock was SOFA on D1 (OR 7.44, 95% CI 1.330-5.715).Neither PCT and CRP threshold values nor their kinetics can predict VAP survival or septic shock development.

Background: Adenosine deaminase (ADA) is a commonly used marker in the diagnosis of tuberculous effusion and there is evidence that its production is linked to T cells and monocytes. Data on the correlation between ADA and T cells or macrophages in tuberculous effusions are conflicting. Furthermore, no studies have examined a possible correlation between pleural tissue infiltration and ADA. Objectives: We undertook this study to examine cell subsets in the fluid and the pleura in tuberculous effusion and their correlation to ADA. The use of cell subsets as a marker in the differential diagnosis was also examined. Methods: Pleural fluid from 36 patients with tuberculous and 34 patients with malignant effusion as well as pleural tissue biopsies from 16 patients with tuberculous pleurisy were examined. The APAAP and the avidin-biotin complex immunocytochemical methods were used to examine CD4+ T cells and macrophages (CD68+), while ADA activity was measured by the Giusti colorimetric method. Results: Our results showed that, in pleural fluid, CD4+ cells and ADA were significantly higher in tuberculous compared to malignant effusion (p < 0.001 for all measurements). In pleural tissue biopsies, macrophages were the predominant cells but CD4+ T cells were also abundant. A significant correlation was found between ADA and CD4+ numbers in pleural fluid and tissue (r = 0.45, p < 0.01; r = 0.75, p < 0.001, respectively). ADA had high sensitivity and specificity for differential diagnosis while cell subsets did not. Conclusions: These results indicate that ADA activity correlates to CD4+ T cell infiltration in the pleura and the fluid. Moreover, ADA but no cell subsets may be used as markers of tuberculous effusion.

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SUMMARY In this study we examined the cytokine production by T cells and TCRVβ subsets in peripheral blood (PB) and synovial fluid (SF) from six RA patients and PB from 10 normal subjects, using three‐colour flow cytometry. In two RA subjects we assessed T cell clonality by RT PCR using TCRBV family‐specific primers and analysed the CDR3 (complementarity determining region 3) length by GeneScan analysis. A high percentage of IFN‐γ‐ and IL‐2‐ producing cells was observed among the PB T cells in both the RA patients and normal controls and among the SF T cells in RA patients. In contrast, the percentage of T cells producing IL‐4 and IL‐5 was small among PB T cells in both RA patients and normal controls and among SF T cells in RA patients. There was no significant difference in the production of IFN‐γ, IL‐2 and IL‐5 between the two compartments (PB and SF); however, there were significantly more IL‐4‐producing cells in SF. Molecular analysis revealed clonal expansions of four TCRBV families in SF of two of the RA patients studied: TCRBV6·7, TCRBV13·1 and TCRBV22 in one and TCRBV6·7, TCRBV21·3 and TCRBV22 in the second. These expansions demonstrated cytokine expression profiles that differed from total CD3+ cells, implying that T cell subsets bearing various TCR‐Vβ families may have the potential to modulate the immune response in RA patients.

Of tumour markers in induced sputum, sputum CYFRA 21-1 offered the best predictive values, although not sufficiently satisfactory to suggest its routine use in lung cancer diagnosis.

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SUMMARY T cells are thought to play an important regulatory role in atopic asthma. We hypothesized that human blood and BAL T cell subsets bearing various TCR-Vβ genes might show selective differences in their cytokine profile. Peripheral blood (PB) and bronchoalveolar lavage (BAL) T cells from seven atopic asthmatic and six non-atopic non-asthmatic subjects were stimulated with PMA and ionomycin in the presence of monensin and analysed for TCR-Vβ expression and production of cytokines at the single cell level. The percentage of IFN-γ- and IL-2-producing BAL T cells was elevated compared with PB T cells from both the asthmatic subjects and the non-atopic, non-asthmatic controls. A small percentage of PB and BAL T cells produced IL-4 and IL-5, in asthmatic and normal subjects. In peripheral blood, the percentage of T cells expressing each cytokine was similar in the various TCR-Vβ subsets and in total CD3+ T cells in all normal and six of seven asthmatic subjects. However, there was a substantial degree of heterogeneity in the cytokine profile of BAL TCR-Vβ subsets compared with the total CD3+ T cells. This was more obvious in the asthmatic subjects with a reduction in the percentage of IFN-γ- and IL-2-expressing T cells (five of seven asthmatic subjects) and an increase in the percentage of IL-4- and IL-5-expressing T cells (two of seven asthmatic subjects). These data confirm previous findings of an elevated proportion of IFN-γ- and IL-2-producing BAL T cells while only a small proportion of PB and BAL T cells produce IL-4 and IL-5. Moreover, subsets of BAL T cells, defined by their TCR-Vβ usage, may differ in their cytokine profile compared with the total CD3+ T cells, implying that T cells expressing different Vβ elements may play different roles in regulating the airway inflammation in asthma.

Severe asthma is a discrete clinical entity characterised by recurrent exacerbations, reduced quality of life and poor asthma control as ordinary treatment regimens remain inadequate. Difficulty in managing severe asthma derives partly from the multiple existing phenotypes and our inability to recognise them. Though the exact pathogenetic pathway of severe allergic asthma remains unclear, it is known that numerous inflammatory cells and cytokines are involved, and eosinophils represent a key inflammatory cell mediator. Anti-IgE (omalizumab) and anti-IL-5 (mepolizumab) antibodies are biological agents that interfere in different steps of the Th2 inflammatory cascade and are licensed in severe asthma. Both exhibit a favourable clinical outcome as they reduce exacerbation rate and improve asthma control and quality of life, while mepolizumab also induces an oral steroid sparing effect. Nevertheless, it is still questionable which agent is more suitable in the management of severe allergic asthma since no comparable studies have been conducted. Omalizumab's established effectiveness in clinical practice over a long period is complemented by a beneficial effect on airway remodelling process mediated mainly through its impact on eosinophils and other parameters strongly related to eosinophilic inflammation. However, it is possible that mepolizumab through nearly depleting eosinophils could have a similar effect on airway remodelling. Moreover, to date, markers indicative of the patient population responding to each treatment are unavailable although baseline eosinophils and exacerbation rate in the previous year demonstrate a predictive value regarding anti-IL-5 therapy effectiveness. On the other hand, a better therapeutic response for omalizumab has been observed when low forced expiratory volume in 1 sec, high-dose inhaled corticosteroids and increased IgE concentrations are present. Consequently, conclusions are not yet safe to be drawn based on existing knowledge, and additional research is necessary to unravel the remaining issues for the severe asthmatic population.