Randomized comparison of awake nonresectional versus nonawake resectional lung volume reduction surgery

ObjectiveThe study objective was to assess in a randomized controlled study (NCT00566839) the comparative results of awake nonresectional or nonawake resectional lung volume reduction surgery.MethodSixty-three patients were randomly assigned by computer to receive unilateral video-assisted thoracic surgery lung volume reduction surgery by a nonresectional technique performed through epidural anesthesia in 32 awake patients (awake group) or the standard resectional technique performed through general anesthesia in 31 patients (control group). Primary outcomes were hospital stay and changes in forced expiratory volume in 1 second. During follow-up, the need of contralateral treatment because of loss of postoperative benefit was considered a failure event as death.ResultsIntergroup comparisons (awake vs control) showed no difference in gender, age, and body mass index. Hospital stay was shorter in the awake group (6 vs 7.5 days, P = .04) with 21 versus 10 patients discharged within 6 days (P = .01). At 6 months, forced expiratory volume in 1 second improved significantly in both study groups (0.28 vs 0.29 L) with no intergroup difference (P = .79). In both groups, forced expiratory volume in 1 second improvements lasted more than 24 months. At 36 months, freedom from contralateral treatment was 55% versus 50% (P = .5) and survival was 81% versus 87% (P = .5).ConclusionsIn this randomized study, awake nonresectional lung volume reduction surgery resulted in significantly shorter hospital stay than the nonawake procedure. There were no differences between study groups in physiologic improvements, freedom from contralateral treatment, and survival. We speculate that compared with the nonawake procedure, awake lung volume reduction surgery can offer similar clinical benefit but a faster postoperative recovery

HLA-DP Allele-Specific T Cell Responses to Beryllium Account for DP-Associated Susceptibility to Chronic Beryllium Disease

Abstract Occupational exposure to small molecules, such as metals, is frequently associated with hypersensitivity reactions. Chronic beryllium (Be) disease (CBD) is a multisystem granulomatous disease that primarily affects the lung, and occurs in ∼3% of individuals exposed to this element. Immunogenetic studies have demonstrated a strong association between CBD and possession of alleles of HLA-DP containing glutamic acid (Glu) at position 69 in the HLA-DPβ-chain. T cell clones were raised from three patients with CBD in whom exposure occurred 10 and 30 years previously. Of 25 Be-specific clones that were obtained, all were restricted by HLA-DP alleles with Glu at DPβ69. Furthermore, the proliferative responses of the clones were absolutely dependent upon DPβ Glu69 in that a single amino acid substitution at this position abolished the response. As befits a disease whose pathogenesis involves a delayed type hypersensitivity response, the large majority of Be-specific clones secreted IFN-γ (Th1) and little or no IL-4 (Th2) cytokines. This study provides insights into the molecular basis of DP2-associated susceptibility to CBD

Analysis of HLA-DP association with beryllium disease susceptibility in pooled exposed populations

Berylliosis or Chronic Beryllium Disease is a chronic granulomatous disorder primarily involving the lung associated with the exposition to low doses of Beryllium (Be) in the workplace. Berylliosis risk has been associated with the presence of a glutamate at position 69 of the HLA-DP beta chain (HLA-DPbetaGlu69) that is expressed in about 97% of disease cases and in 27% of the unaffected Be-exposed controls (p<0.0001) (Richeldi et al. Science 1993; 262: 242-244.12). Since this first observation of an immunogenetic association between berylliosis and HLA-DPbetaGlu69 a number of studies have confirmed the role of this marker as the primary gene of susceptibility of berylliosis (Richeldi et al Am J Ind Med. 1997; 32:337-40; Wang et al J. Immunol. 1999; 163: 1647-53; Saltini et al Eur Respir J. 2001 18:677-84; Rossman et al Am J Respir Crit Care Med. 2002 165:788-94). Moreover, a structure/function interaction between HLA-DP molecules carrying Glu69 and beryllium in driving and developing the immune response against beryllium itself has been observed as: (1) Be-specific T-cells clones obtained from berylliosis patients recognize beryllium as antigen only when presented in the context of the HLA-DP{beta}Glu69 molecules but not in the context of HLA-DP allelic variants carrying Lys69 (Lombardi G et al. J Immunol 2001; 166: 3549-3555), and (2) beryllium presents an affinity for the HLA-DP2, carrying the berylliosis marker of susceptibility HLA-DPGlu69, from 40 to 100 times higher that the HLA-DP molecule carrying Lys69 (Amicosante M. et al Hum. Immunol. 2001; 62: 686-93). However, although the immunogenetic studies performed have been addressed a number of different questions about the genetic association between berylliosis and/or beryllium sensitization, exposure levels to beryllium and HLA markers, a number of questions are still open in the field mainly due to the limitation imposed by the low number of subjects carrying berylliosis or beryllium sensitization enrolled in each immunogenetic study. In this context, the populations of the study already performed in this field by the University of Modena and Rome (by Prof. C. Saltini) and the University of Pennsylvania (by Prof. M. Rossman) have been evaluated by using similar HLA molecular typing methodologies and that both populations have now been followed up for a period of 4 to 7 years. The general objective of this study has to generate a larger data base comprising the two population with which analyze gene disease association with greater statistical power and ascertain the effect of lesser common gener variants which may be missed when analyzing associations on small populations. In particular addressing the role suggested in previous study such as: (1) the role of HLA-DP rare alleles and polymorphisms, and (2) the role of the HLA markers in disease progression from sensitization. The two populations from the already published studies (Saltini et al Eur Respir J. 2001 18:677-84; Rossman et al Am J Respir Crit Care Med. 2002 165:788-94) present similar aspects about: ethnicity, type and length of exposure to Be dust, a broadly similar association between beryllium related abnormalities and HLA. The two population have been pooled and evaluated using common criteria of diagnosis (Sensitized subject: at least 2 positive BeLPT tests each with 2 positive wells; CBD-affected subject: identification of well formed non-caseating granulomas on biopsy), follow up and HLA typing technique (complete HLA-DRB, DQB, DPB high resolution typing using amplification with sequence specific primers or sequence based typing). The two populations included 137 subjects with Beryllium hypersensitized (BH) and 155 Be-exposed controls. Inclusion criteria were met by one hundred and six subjects with Be-hypersensitivity of whom 55 were affected by CBD (age 52 {+-} 11 years; 50 caucasians, 2 African-Americans 2 Hispanics and 1 Asian; 46 males and 9 females; mean duration of Be-exposure 15 {+-} 9 years) and 51 showed Be-sensitization without lung granulomas detected by trans-bronchial biopsy (age 54 {+-} 14 years; 47 Caucasians, 3 Hispanics and 1 Afro-American; 45 males and 6 females; mean age of Be-exposure 17 {+-} 10 years) and 129 Be-exposed controls (age 53 {+-} 14 years; 120 Caucasians, 4 African-American, 4 Hispanics, 1 Asian; 104 males and 25 females; mean duration of Be-exposure 16 {+-} 10 years). Mean follow-up of BH affected subjects was 7.0 {+-} 3.7 years from the first positive Be-LPT test

Immunogenetics of severe respiratory infections: Models for the development of new therapeutic strategies

Innate and adaptive immunity plays a critical role in the defence of the lung and other mucosal surfaces exposed to micro-organisms. Anti-microbial peptides and proteins, cytokines and chemokines are important immune weapons as they build up the protective front for the respiratory tract. The notion that susceptibility to infectious diseases may be inherited is widely accepted and, as it is the failure to activate adaptive immunity that may allow infection to become established and progress toward invasion and dissemination, the recognition of specific gene defects affecting the ability of the immune system to overcome invading pathogens may shed light upon those mechanisms of immune regulation that are playing the most critical roles. The aim of the present review is to discuss some of the advances in infection immunogenetics that may lead to identify new strategies in the development of new anti-infectious and anti-inflammatory drugs. Copyright © 2005 S. Karger AG

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Sensitivity and specificity of a multi-antigen ELISA test for the serological diagnosis of tuberculosis

A new serological assay (DETECT-TB, BioChem ImmunoSystems), using three recombinant proteins and two synthetic peptides for the detection of the anti-Mycobacterium tuberculosis IgG, was evaluated using a panel of serum specimens collected from 100 tuberculosis (TB) patients and 270 controls, in comparison with a homemade ELISA test using purified protein derivative (PPD) as antigen. DETECT-TB presented a higher sensitivity (75%) compared to PPD-ELISA (56%; P 0.80). Receiver operating characteristics (ROC) analysis obtained with these data confirmed the higher level of performance of DETECT-TB in comparison with PPD-ELISA. Considering the rapidity, cost-effectiveness and simplicity of this assay, its use may provide useful clinical information aiding in the rapid diagnosis of difficult TB cases