RESUMO
PURPOSE: Epidemiological studies have suggested that indoor hospital employees, either day or night shift workers, are at high risk of metabolic and cardiovascular diseases. Interestingly, previous reports have also described a higher prevalence of vitamin D (25OHD) deficiency among these workers. However, few studies have determined the monthly variations in 25OHD levels in indoor hospital employees. METHODS: To address this lack of knowledge, in 2018, during the periodic health surveillance checks at the Service of Occupational Medicine, we measured 25OHD levels in a group of indoor hospital workers (88 rotating night shift workers vs 200 day workers). Each participant received a single annual health surveillance check. RESULTS: The mean levels of 25OHD were consistently below the lower limit of the normal range in both groups throughout the year. Only in the summer, day workers but not rotating night shift workers (mean 25.9 ± 11.3 ng/ml vs 23.1 ± 9.1 ng/ml; p = 0.042) showed levels significantly higher than those in the other seasons. This difference remained statistically significant even after correction for study covariates [ß = - 1.649 (CI - 0.283/- 3.482), p = 0.039]. A cosinor analysis confirmed that the difference in the 25OHD levels between groups was present later in the year. CONCLUSIONS: We found that relatively young healthy hospital workers, especially those with rotating night shifts, in the absence of significant metabolic risk factors, have a high risk of 25OHD deficiency/insufficiency. Because 25OHD deficiency may lead to a progression to more severe conditions such as osteoporosis or bone fractures, our results should be verified in larger cohorts including different ancestries.
Assuntos
Ritmo Circadiano/fisiologia , Recursos Humanos em Hospital , Jornada de Trabalho em Turnos , Vitamina D/análogos & derivados , Adulto , Feminino , Hospitais/estatística & dados numéricos , Humanos , Itália/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/epidemiologia , Recursos Humanos em Hospital/estatística & dados numéricos , Fatores de Risco , Estações do Ano , Jornada de Trabalho em Turnos/estatística & dados numéricos , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Adulto JovemRESUMO
OBJECTIVES: Our objective was to evaluate factors associated with recurrence in patients with 027+ and 027- Clostridium difficile infection (CDI). METHODS: Patients with CDI observed between January and December 2014 in six hospitals were consecutively included in the study. The 027 ribotype was deduced by the presence of tcdB, tcdB, cdt genes and the deletion Δ117 in tcdC (Xpert® C. difficile/Epi). Recurrence was defined as a positive laboratory test result for C. difficile more than 14 days but within 8 weeks after the initial diagnosis date with reappearance of symptoms. To identify factors associated with recurrence in 027+ and 027- CDI, a multivariate analysis was performed in each patient group. Subdistributional hazard ratios (sHRs) and 95% confidence intervals (95%CIs) were calculated. RESULTS: Overall, 238 patients with 027+ CDI and 267 with 027- CDI were analysed. On multivariate analysis metronidazole monotherapy (sHR 2.380, 95%CI 1.549-3.60, p <0.001) and immunosuppressive treatment (sHR 3.116, 95%CI 1.906-5.090, p <0.001) were factors associated with recurrence in patients with 027+ CDI. In this patient group, metronidazole monotherapy was independently associated with recurrence in both mild/moderate (sHR 1.894, 95%CI 1.051-3.410, p 0.033) and severe CDI (sHR 2.476, 95%CI 1.281-4.790, p 0.007). Conversely, non-severe disease (sHR 3.704, 95%CI 1.437-9.524, p 0.007) and absence of chronic renal failure (sHR 16.129, 95%CI 2.155-125.000, p 0.007) were associated with recurrence in 027- CDI. CONCLUSIONS: Compared to vancomycin, metronidazole monotherapy appears less effective in curing CDI without relapse in the 027+ patient group, independently of disease severity.
Assuntos
Antibacterianos/uso terapêutico , Clostridioides difficile/genética , Infecções por Clostridium/epidemiologia , Metronidazol/uso terapêutico , Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Clostridioides difficile/classificação , Clostridioides difficile/efeitos dos fármacos , Infecções por Clostridium/microbiologia , Infecções por Clostridium/patologia , Humanos , Recidiva , Proteínas Repressoras/genéticaRESUMO
PURPOSE: There are few data in the literature regarding sepsis or septic shock due to extended-spectrum ß-lactamases (ESBL)-producing Enterobacteriaceae (E). The aim of this study was to assess predictors of outcome in septic patients with bloodstream infection (BSI) caused by ESBL-E. METHODS: Patients with severe sepsis or septic shock and BSI due to ESBL-E were selected from the INCREMENT database. The primary endpoint of the study was the evaluation of predictors of outcome after 30 days from development of severe sepsis or septic shock due to ESBL-E infection. Three cohorts were created for analysis: global, empirical-therapy and targeted-therapy cohorts. RESULTS: 367 septic patients were analysed. Overall mortality was 43.9% at 30 days. Escherichia coli (62.4%) and Klebsiella pneumoniae (27.2%) were the most frequent isolates. ß-lactam/ß-lactamase inhibitor (BLBLI) combinations were the most empirically used drug (43.6%), followed by carbapenems (29.4%). Empirical therapy was active in vitro in 249 (67.8%) patients, and escalation of antibiotic therapy was reported in 287 (78.2%) patients. Cox regression analysis showed that age, Charlson Comorbidity Index, McCabe classification, Pitt bacteremia score, abdominal source of infection and escalation of antibiotic therapy were independently associated with 30-day mortality. No differences in survival were reported in patients treated with BLBLI combinations or carbapenems in empirical or definitive therapy. CONCLUSIONS: BSI due to ESBL-E in patients who developed severe sepsis or septic shock was associated with high 30-day mortality. Comorbidities, severity scores, source of infection and antibiotic therapy escalation were important determinants of unfavorable outcome.
Assuntos
Técnicas de Apoio para a Decisão , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/mortalidade , Enterobacteriaceae/enzimologia , Sepse/diagnóstico , Sepse/mortalidade , beta-Lactamases/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sepse/tratamento farmacológico , Sepse/microbiologia , Análise de Sobrevida , Resultado do Tratamento , Inibidores de beta-Lactamases/uso terapêutico , beta-Lactamas/uso terapêuticoRESUMO
OBJECTIVE: The central nervous system (CNS) may be involved in a variety of inflammatory diseases of the blood vessels, generally known as vasculitis. The clinical diagnosis of such involvement in early stages is difficult, since a mild cognitive impairment can be the only symptom. It was hypothesized that brain-perfusion SPECT would be able to reveal CNS involvement and to monitor the course of the disease. The purpose of this study was assess if and when an improvement of cerebral perfusion can be registered by SPECT during the follow-up of these diseases. MATERIAL AND METHODS: Eighteen patients affected by Systemic Lupus Erythematosus (SLE), 22 by undifferentiated vasculitis (UV), 5 by Behcet's disease (BD) and 5 by primary Sjogren's Syndrome (pSS) were enrolled in this prospective study. A 99mTc-HMPAO brain perfusion SPECT was performed before the treatment and was repeated during the follow-up at different time intervals. Image analysis was performed on 10 cerebral areas using a specific software. RESULTS: In the SLE patients, no significant improvement of brain perfusion was found. On the contrary, in the UV the cerebral uptake of the tracer significantly improved from the twenty-fourth month (18/22 patients). Patients with BD showed an improvement of scintigraphic findings (5/5 patients), while a similar result was obtained only in 2 of the patients with pSS. CONCLUSIONS: In conclusion, brain SPECT seems to be able to monitor the disease in UV, indicating the moment when an improvement of the cerebral perfusion is achieved. In SLE patients this scintigraphic technique did not show a significant improvement in CNS perfusion.
Assuntos
Encéfalo/diagnóstico por imagem , Neuroimagem/métodos , Compostos Radiofarmacêuticos/farmacocinética , Tecnécio Tc 99m Exametazima/farmacocinética , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Vasculite do Sistema Nervoso Central/diagnóstico por imagem , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Adulto , Síndrome de Behçet/complicações , Síndrome de Behçet/tratamento farmacológico , Encéfalo/irrigação sanguínea , Circulação Cerebrovascular/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Monitoramento de Medicamentos , Feminino , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Testes Neuropsicológicos , Estudos Prospectivos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/tratamento farmacológico , Resultado do Tratamento , Vasculite do Sistema Nervoso Central/tratamento farmacológico , Vasculite do Sistema Nervoso Central/etiologia , Vasculite do Sistema Nervoso Central/psicologiaRESUMO
BACKGROUND: An increasing prevalence of candidemia has been reported in Internal Medicine wards (IMWs). The aim of our study was to identify risk factors for candidemia among non-neutropenic patients hospitalized in IMWs. METHODS: A multicenter case-control study was performed in three hospitals in Italy. Patients developing candidemia (cases) were compared to patients without candidemia (controls) matched by age, time of admission and duration of hospitalization. A logistic regression analysis identified risk factors for candidemia, and a new risk score was developed. Validation was performed on an external cohort of patients. RESULTS: Overall, 951 patients (317 cases of candidemia and 634 controls) were included in the derivation cohort, while 270 patients (90 patients with candidemia and 180 controls) constituted the validation cohort. Severe sepsis or septic shock, recent Clostridium difficile infection, diabetes mellitus, total parenteral nutrition, chronic obstructive pulmonary disease, concomitant intravenous glycopeptide therapy, presence of peripherally inserted central catheter, previous antibiotic therapy and immunosuppressive therapy were factors independently associated with candidemia. The new risk score showed good area under the curve (AUC) values in both derivation (AUC 0.973 95% CI 0.809-0.997, p<0.001) and validation cohort (0.867 95% CI 0.710-0.931, p<0.001). A threshold of 3 leads to a sensitivity of 87% and a specificity of 83%. CONCLUSION: Non-neutropenic patients admitted in IMWs have peculiar risk factors for candidemia. A new risk score with a good performance could facilitate the identification of candidates to early antifungal therapy.
Assuntos
Candidemia/epidemiologia , Infecção Hospitalar/epidemiologia , Hospitalização , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Candida , Candidemia/tratamento farmacológico , Estudos de Casos e Controles , Infecção Hospitalar/microbiologia , Feminino , Hospitais , Humanos , Medicina Interna , Itália/epidemiologia , Modelos Logísticos , Masculino , Estudos Retrospectivos , Fatores de RiscoAssuntos
Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/epidemiologia , Diarreia/epidemiologia , Casas de Saúde , Ribotipagem , Idoso , Idoso de 80 Anos ou mais , Clostridioides difficile/classificação , Clostridioides difficile/genética , Infecções por Clostridium/microbiologia , Diarreia/microbiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Epidemiologia Molecular , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
The aim of this study was to identify factors associated with mortality in intensive care unit patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) septic shock. A retrospective analysis of intensive care unit patients with KPC-Kp infection and septic shock observed in a large teaching hospital from November 2010 to December 2014 was performed. A total of 111 patients were included in the study. The most frequent source of infection was unknown-focus bacteraemia in 53 patients (47.7%). The rate of resistance to colistin was 51.3%; 30-day mortality was reported for 44 patients (39.6%). Surviving patients were more frequently treated with an initial therapy (within 24 hours) including two or more antibiotics displaying in vitro activity against the isolated KPC-Kp strain (41.8 vs. 18.1%, p 0.01) and were also more likely to receive a definitive therapy including two or more in vitro active antibiotics (85.1 vs. 15.9%, p <0.001). Cox regression analysis revealed that a colistin-containing antibiotic regimen (hazard ratio (HR) 0.21, confidence interval (CI) 95% 0.05-0.72, p <0.001), use of two or more in vitro active antibiotics as definite therapy (HR 0.08, CI 95% 0.02-0.21, p <0.001) and control of removable source of infection (HR 0.14, CI 95% 0.04-0.25, p <0.001) were associated with favourable outcome; colistin resistance (HR 8.09, CI 95% 3.14-11.23, p 0.001) and intra-abdominal source of infection (HR 2.92, CI 95% 2.11-4.12, p 0.002) were associated with death. In conclusion, use of a definitive therapy with at least two antibiotics displaying in vitro activity against the KPC-Kp isolates was the most important determinant of favourable outcome, whilst isolation of colistin-resistant strains was associated with death in septic patients with KPC-Kp infection.
Assuntos
Antibacterianos/uso terapêutico , Proteínas de Bactérias/metabolismo , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/enzimologia , Choque Séptico/tratamento farmacológico , Choque Séptico/mortalidade , beta-Lactamases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais de Ensino , Humanos , Unidades de Terapia Intensiva , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Choque Séptico/microbiologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
We propose an Mhotb model for population size estimation in capture-recapture studies. The tb part is based on equality constraints for the conditional capture probabilities, leading to an extremely rich model class. Observed and unobserved heterogeneity are dealt with by means of a logistic parameterization. In order to explore the model class, we introduce a penalized version of the likelihood. The conditional likelihood and penalized conditional likelihood are maximized by means of efficient EM algorithms. Simulations and two real data examples illustrate the approach.
Assuntos
Algoritmos , Censos , Interpretação Estatística de Dados , Modificador do Efeito Epidemiológico , Modelos Estatísticos , Densidade Demográfica , Animais , Biometria/métodos , Simulação por Computador , Humanos , Funções Verossimilhança , Reprodutibilidade dos Testes , Tamanho da Amostra , Sensibilidade e EspecificidadeRESUMO
Recent studies involving a limited number of patients have indicated a correlation between aneuploidy and various morphokinetic parameters during preimplantation development. The results among different groups, however, have been inconsistent in identifying the parameters that are able to predict chromosomal abnormalities. The aim of this study was to investigate whether aneuploidy of human blastocysts was detectable by specific morphokinetic parameters in patients at increased risk of aneuploidy because of advanced maternal age, history of unsuccessful IVF treatments, or both. A longitudinal cohort study was conducted using 455 blastocysts from 138 patients. Morphokinetic features of preimplantation development were detected in a timelapse incubator. Blastocysts were subjected to trophectodermal biopsy and comprehensive chromosomal screening. Analyses were conducted by means of logistic mixed-effects models, with a subject-specific intercept. No statistical correlation between 16 commonly detected morphokinetic characteristics of in-vitro embryo development and aneuploidy was found. Results suggest that morphokinetic characteristics cannot be used to select euploid blastocysts in poor-prognosis patients regarded as candidates for pre-implantation genetic screening.
Assuntos
Aneuploidia , Blastocisto/citologia , Desenvolvimento Embrionário , Biópsia , Aberrações Cromossômicas , Transferência Embrionária/métodos , Feminino , Fertilização in vitro/métodos , Humanos , Estudos Longitudinais , Oócitos/citologia , Indução da Ovulação , Reação em Cadeia da Polimerase , Diagnóstico Pré-Implantação/métodos , Prognóstico , Análise de RegressãoRESUMO
We propose a multiple testing procedure controlling the false discovery rate. The procedure is based on a possibly data driven ordering of the hypotheses, which are tested at the uncorrected level q until a suitable number is not rejected. When the order is data driven, larger effect sizes are considered first, therefore selecting more interesting hypotheses with larger probability. The proposed procedure is valid under independence for the test statistics. We also propose a modification which makes our procedure valid under arbitrary dependence. It is shown in simulation that we compare particularly well when the sample size is small. We conclude with an application to identification of molecular signatures of intracranial ependymoma. The methods are implemented in an R package (someMTP), freely available on CRAN.
Assuntos
Biometria/métodos , Modelos Estatísticos , Algoritmos , Neoplasias Encefálicas/genética , Hibridização Genômica Comparativa/estatística & dados numéricos , Simulação por Computador , Ependimoma/genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/estatística & dados numéricos , Análise de RegressãoRESUMO
OBJECTIVE: Polycystic ovary syndrome (PCOS) is a frequent condition, affecting about 15% of women of reproductive age. Because of its familial occurrence, a multifactorial model of susceptibility, including both genetic and environmental factors, has been proposed. However, the identification of genetic factors has been elusive. DESIGN: Case-control study aimed at evaluating possible associations between functionally relevant variants of the luteinizing hormone/choriogonadotrophin receptor gene (LHCGR) and PCOS phenotype. PATIENTS: A total of 198 PCOS and 187 non-PCOS women, aged 14-35 years, of Sardinian origin, were referred to the outpatient clinic of the Department of Obstetrics and Gynaecology of the University of Cagliari (Sardinia). PCOS diagnosis was based on the Rotterdam criteria. MEASUREMENTS: We determined the genotype of ins18LQ, S291N and S312N variants at the LHCGR locus. Genotype was related to the presence or absence of PCOS and to several clinical and biochemical characteristics. RESULTS: The presence of at least one 312N allele was strongly associated with PCOS risk (OR, 2·04; 95% CI, 1·32-3·14; χ(2) , 10·47; P = 0·001). 312N homozygosity was associated with a further risk increase (OR, 2·73; 95% CI, 1·25-5·95; χ(2) , 6·65; P = 0·01). The number of ins18LQ alleles was associated with LH serum levels in controls (χ(2) , 8·04, P = 0·017). CONCLUSIONS: For the first time, we have identified a genetic variant that is strongly associated with PCOS in an isolated population. These results, if confirmed in other cohorts, may provide the opportunity to test the S312N genotype at the LHCGR locus in fertile women to assess the risk of PCOS. The avoidance of triggering factors like weight increase may improve the reproductive outcome of potentially at-risk subjects.
Assuntos
Predisposição Genética para Doença , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único , Receptores do LH/genética , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genética Populacional , Humanos , Itália/epidemiologia , Síndrome do Ovário Policístico/epidemiologia , Polimorfismo de Nucleotídeo Único/fisiologia , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Circulating tumor cells (CTCs) provide prognostic information in patients with metastatic tumors. Recent studies have shown that CTCs are released in circulation in an early phase of cancer disease so that their presence is under investigation in the adjuvant setting. Few studies investigated the prognostic significance of CTCs enumeration in patients with metastatic and advanced bladder cancer. The current study has analyzed the presence of CTC in patients with nonmuscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Forty-four NMIBC patients were enrolled and included in a 24-month follow-up program. Blood drawings were carried out in all patients at the first diagnosis. CellSearch system (Veridex; LLC, Raritan, NJ) was used for CTCs enumeration. RESULTS: CTC were detectable in 8/44 patients (18%). Presence of CTC was found significantly associated to shorter time to first recurrence (6.5 versus 21.7 months, P < 0.001). Median time to progression was not reached, due to the short follow-up period. CTC presence was found associated to concomitant carcinoma in situ and higher T category. CONCLUSION: The detection of CTC in this setting of disease may allow to distinguish patients with high risk of recurrence from those with high risk of progression, as well as to early identify patients candidate for adjuvant treatment.
Assuntos
Carcinoma de Células de Transição/patologia , Recidiva Local de Neoplasia , Células Neoplásicas Circulantes/patologia , Neoplasias da Bexiga Urinária/patologia , Idoso , Estudos de Casos e Controles , Contagem de Células , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Separação Imunomagnética , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Prospectivos , Resultado do TratamentoRESUMO
We show a novel approach for k-FWER control which does not involve any correction, but only testing the hypotheses along a (possibly data-driven) order until a suitable number of p-values are found above the uncorrected α level. p-values can arise from any linear model in a parametric or nonparametric setting. The approach is not only very simple and computationally undemanding, but also the data-driven order enhances power when the sample size is small (and also when k and/or the number of tests is large). We illustrate the method on an original study about gene discovery in multiple sclerosis, in which were involved a small number of couples of twins, discordant by disease. The methods are implemented in an R package (someKfwer), freely available on CRAN.
Assuntos
Algoritmos , Marcadores Genéticos/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Esclerose Múltipla/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Gêmeos/genética , Feminino , Humanos , Itália/epidemiologia , MasculinoRESUMO
BACKGROUND: Labor pain has a sensory and an affective component. This study was undertaken to evaluate whether the quality and intensity of the cognitive descriptors of labor pain may be influenced by parity and stage of labor. METHODS: One hundred and eighty-four parturients were divided into four groups according to parity (nulliparous and multiparous women) and stage of labor (early and late) and were given a modified version of the short-form McGill Pain Questionnaire that included the 23 most frequently reported labor pain descriptors. In addition, parturients were asked to report intensity of pain on a visual analogue pain scale and using the present pain intensity index. RESULTS: The most frequent descriptors used were cramping, pulling, hot, stinging, aching, heavy, tiring, exhausting and unbearable. The descriptors, "tiring" and "exhausting", were used primarily by nulliparous women (P <0.001). The intensity of "cramping", "stinging" and "aching" was greater in nulliparous women (P <0.0001) and the intensity of "heavy", "stinging", and "aching" increased as labor progressed in both groups (P <0.001). Mean intensity of pain increased as cervical dilation increased in both nulliparous and multiparous women. The visual analogue pain scale and present pain intensity index were strongly correlated (tau=0.63; P <0.0001). Low fetal station was associated with greater pain scores in nulliparous women (P<0.026). CONCLUSIONS: Affective and cognitive components of labor pain are frequently communicated with a restricted number of pain descriptors and may be affected by obstetric variables. An understanding of labor pain in a multidimensional framework provides the basis for a woman-centered approach to labor pain management.
Assuntos
Dor do Parto/fisiopatologia , Primeira Fase do Trabalho de Parto , Terceira Fase do Trabalho de Parto , Paridade , Adulto , Feminino , Humanos , Dor do Parto/psicologia , Medição da Dor , Gravidez , Transtornos de Sensação/etiologia , Transtornos de Sensação/fisiopatologia , Transtornos de Sensação/psicologia , Inquéritos e Questionários , Terminologia como Assunto , Resultado do TratamentoRESUMO
Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis conductance transmembrane regulator (CFTR). Symptoms are pancreatic insufficiency, chronic obstructive lung disease, liver disease, chronic sinusitis and infertility in male patients. The phenotypic variability may be explained only in part by the more than 1200 CFTR mutations, which are grouped into six different classes, according to their effect on the protein ranging from a severe (no synthesis or blocked processing) to mild mutation (altered conductance or reduced synthesis). However, it is now accepted that other genes (CF modifiers) influence the phenotypic spectrum of the disease. In order to identify CF modifier genes, we built a low-density home-made oligoarray containing 144 genes selected according to biochemical criteria and evaluated their expression in two CF bronchial epithelial cell lines (CuFi1 F508del/F508del; CuFi3 F508del/R553X). If we consider both cell lines, 38 genes (26.3%) show an altered expression pattern with a threshold > +/-1.5. Of these 38 genes, 12 are altered in CuFi1, and 26 in CuFi3. Some of these genes share the same expression pattern in both cell lines, while others have a different behaviour. These results were validated by a QRT-PCR assay (R2 CuFi1 = 0.81 and R2 CuFi3 = 0.91). These data could suggest that the presence of a class I allele (R553X) determines a more profound alteration of gene expression pattern than the presence of a class II allele (F508del). The identification of the genes altered by a specific CF mutation could lead to the development of a pharmacological approach specific for different CFTR genotypes.