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1.
Sci Rep ; 11(1): 23955, 2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34907223

RESUMO

Asbestos is considered the main cause of diseases in workers exposed to this mineral in the workplace as well as an environmental pollutant. The association between asbestos and the onset of different diseases has been reported, but asbestos exposure specific biomarkers are not known. MicroRNAs (miRNAs) are small, single-strand, non-coding RNAs, with potential value as diagnostic, prognostic, and predictive markers in liquid biopsies. Sera collected from workers ex-exposed to asbestos (WEA) fibers were compared with sera from healthy subjects (HS) of similar age, as liquid biopsies. The expression of the circulating miRNA 197-3p was investigated employing two different highly analytical PCR methods, i.e. RT-qPCR and ddPCR. MiR-197-3p levels were tested in sera from WEA compared to HS. MiR-197-3p tested dysregulated in sera from WEA (n = 75) compared to HS (n = 62). Indeed, miR-197-3p was found to be 2.6 times down-regulated in WEA vs. HS (p = 0.0001***). In addition, an inverse correlation was detected between miR-197-3p expression level and cumulative asbestos exposure, being this miRNA down-regulated 2.1 times in WEA, with high cumulative asbestos exposure, compared to WEA with low exposure (p = 0.0303*). Circulating miR-197-3p, found to be down regulated in sera from WEA, is proposed as a new potential biomarker of asbestos exposure.


Assuntos
Amianto/toxicidade , MicroRNA Circulante/sangue , MicroRNAs/sangue , Exposição Ocupacional/efeitos adversos , Idoso , Biomarcadores/sangue , MicroRNA Circulante/genética , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade
2.
Sci Rep ; 11(1): 12848, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145303

RESUMO

Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term "response to bacterium" was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term "response to stress" was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.


Assuntos
Suscetibilidade a Doenças , Expressão Gênica , Leucócitos/metabolismo , Mitocôndrias/genética , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Mucosa Respiratória/metabolismo , Biomarcadores , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Humanos , Fator 4 Semelhante a Kruppel , Leucócitos/imunologia , Leucócitos/patologia , Masculino , Mitocôndrias/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/patologia , Fatores Sexuais , Transcriptoma
3.
Lancet Microbe ; 2(7): e300-e310, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-35544166

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with airway inflammation and bacterial dysbiosis. The relationship between the airway microbiome and bronchial gene expression in COPD is poorly understood. We aimed to identify differences in the airway microbiome from bronchial brushings in patients with COPD and healthy individuals and to investigate whether any distinguishing bacteria are related to bronchial gene expression. METHODS: For this 16S rRNA gene sequencing and host transcriptomic analysis, individuals aged 45-75 years with mild-to-moderate COPD either receiving or not receiving inhaled corticosteroids and healthy individuals in the same age group were recruited as part of the Emphysema versus Airways Disease (EvA) consortium from nine centres in the UK, Germany, Italy, Poland, and Hungary. Individuals underwent clinical characterisation, spirometry, CT scans, and bronchoscopy. From bronchoscopic bronchial brush samples, we obtained the microbial profiles using 16S rRNA gene sequencing and gene expression using the RNA-Seq technique. We analysed bacterial genera relative abundance and the associations between genus abundance and clinical characteristics or between genus abundance and host lung transcriptional signals in patients with COPD versus healthy individuals, and in patients with COPD with versus without inhaled corticosteroids treatment. FINDINGS: Between February, 2009, and March, 2012, we obtained brush samples from 574 individuals. We used 546 of 574 samples for analysis, including 207 from healthy individuals and 339 from patients with COPD (192 with inhaled corticosteroids and 147 without). The bacterial genera that most strongly distinguished patients with COPD from healthy individuals were Prevotella (median relative abundance 33·5%, IQR 14·5-49·4, in patients with COPD vs 47·7%, 31·1-60·7, in healthy individuals; p<0·0001), Streptococcus (8·6%, 3·8-15·8, vs 5·3%, 3·0-10·1; p<0·0001), and Moraxella (0·05%, 0·02-0·14, vs 0·02%, 0-0·07; p<0·0001). Prevotella abundance was inversely related to COPD severity in terms of symptoms and positively related to lung function and exercise capacity. 446 samples had assessable RNA-seq data, 257 from patients with COPD (136 with inhaled corticosteroids and 121 without) and 189 from healthy individuals. No significant associations were observed between lung transcriptional signals from bronchial brushings and abundance of bacterial genera in patients with COPD without inhaled corticosteroids treatment and in healthy individuals. In patients with COPD treated with inhaled corticosteroids, Prevotella abundance was positively associated with expression of epithelial genes involved in tight junction promotion and Moraxella abundance was associated with expression of the IL-17 and TNF inflammatory pathways. INTERPRETATION: With increasing severity of COPD, the airway microbiome is associated with decreased abundance of Prevotella and increased abundance of Moraxella in concert with downregulation of genes promoting epithelial defence and upregulation of pro-inflammatory genes associated with inhaled corticosteroids use. Our work provides further insight in understanding the relationship between microbiome alteration and host inflammatory response, which might lead to novel therapeutic strategies for COPD. FUNDING: EU Seventh Framework Programme, National Institute for Health Research.


Assuntos
Microbiota , Doença Pulmonar Obstrutiva Crônica , Corticosteroides/uso terapêutico , Bactérias/genética , Genes de RNAr , Humanos , Pulmão/microbiologia , Microbiota/genética , Moraxella/genética , Prevotella/genética , Doença Pulmonar Obstrutiva Crônica/genética , RNA Ribossômico 16S/genética , Escarro/microbiologia , Transcriptoma
4.
Artigo em Inglês | MEDLINE | ID: mdl-32627764

RESUMO

Work-related asthma (WRA) includes heterogeneous conditions, which have in common (i) symptoms and signs compatible with asthma and (ii) a relationship with exposures in the workplace. The types of WRA described in this review are distinguished by their etiology, comprising of work-exacerbated asthma (WEA), irritant-induced asthma (IIA), and immunologic occupational asthma (OA). There have been significant advances in the definition and characterization of the different forms of WRA by international panels of experts. The present review provides a comprehensive and updated view of the current knowledge on causes and phenotypes of WRA. Health care practitioners should consider WRA in any case of adult asthma, given that one fifth of workers with asthma report symptoms of WEA and it has been estimated that OA represents 10% to 25% of asthma in adulthood. The information provided in this review will facilitate the physician in the recognition of the different forms of WRA, since it has been established that five categories of agents are responsible for at least 60% of WEA cases and seven groups of agents are the cause of 70% of immunologic OA. In addition, there is agreement that IIA can be elicited not only by a single massive irritant exposure, but also by low/moderate repeated irritant exposures.


Assuntos
Asma Ocupacional , Doenças Profissionais , Exposição Ocupacional , Fenótipo , Adulto , Asma Ocupacional/epidemiologia , Asma Ocupacional/etiologia , Humanos , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Local de Trabalho
5.
Allergy ; 75(2): 370-380, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31506971

RESUMO

BACKGROUND: Whether the clinical or pathophysiologic significance of the "treatable trait" high blood eosinophil count in COPD is the same as for asthma remains controversial. We sought to determine the relationship between the blood eosinophil count, clinical characteristics and gene expression from bronchial brushings in COPD and asthma. METHODS: Subjects were recruited into a COPD (emphysema versus airway disease [EvA]) or asthma cohort (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes, U-BIOPRED). We determined gene expression using RNAseq in EvA (n = 283) and Affymetrix microarrays in U-BIOPRED (n = 85). We ran linear regression analysis of the bronchial brushings transcriptional signal versus blood eosinophil counts as well as differential expression using a blood eosinophil > 200 cells/µL as a cut-off. The false discovery rate was controlled at 1% (with continuous values) and 5% (with dichotomized values). RESULTS: There were no differences in age, gender, lung function, exercise capacity and quantitative computed tomography between eosinophilic versus noneosinophilic COPD cases. Total serum IgE was increased in eosinophilic asthma and COPD. In EvA, there were 12 genes with a statistically significant positive association with the linear blood eosinophil count, whereas in U-BIOPRED, 1197 genes showed significant associations (266 positive and 931 negative). The transcriptome showed little overlap between genes and pathways associated with blood eosinophil counts in asthma versus COPD. Only CST1 was common to eosinophilic asthma and COPD and was replicated in independent cohorts. CONCLUSION: Despite shared "treatable traits" between asthma and COPD, the molecular mechanisms underlying these clinical entities are predominately different.


Assuntos
Asma/genética , Asma/imunologia , Eosinófilos/imunologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/imunologia , Mucosa Respiratória/imunologia , Transcriptoma , Idoso , Asma/sangue , Biomarcadores/sangue , Feminino , Humanos , Imunoglobulina E/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/sangue , RNA-Seq , Células Th2/imunologia
6.
Hum Immunol ; 81(4): 151-155, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31806379

RESUMO

Heart failure (HF) is a syndrome caused by structural and/or functional cardiac abnormalities, resulting in a reduced cardiac output and/or elevated intracardiac pressures. Several studies reported a crucial role of immune activation and inflammation in the chronic heart failure (HF) pathogenesis, suggesting that pro-inflammatory and anti-inflammatory mediators could be predictive markers of the HF development and/or progression. Human Leukocyte Antigen-G (HLA-G), a tolerogenic and anti-inflammatory class I non-classical major histocompatibility complex molecule, was reported to be upregulated in patients diagnosed with HF, suggesting a tentative to regulate the inflammatory condition. We evaluated soluble (s)HLA-G plasmatic levels in patients with stable chronic heart failure at baseline visit and after 6 and 12 months. The 14 bp Insertion/Deletion polymorphisms of the HLA-G gene was also analyzed. We showed that in HF subjects, sHLA-G levels were higher in NYHA class II and III subjects (mild-severe symptoms) (6.11 ± 1.15 ng/ml; 8.25 ± 2.27 ng/ml, respectively) in comparison with NYHA class I subjects (no symptoms) (2.35 ± 0.43 ng/ml) (I vs II: p = 0.0156; I vs III: p = 0.0122). Moreover, the exposure to chemicals seems to affect sHLA-G levels, with higher sHLA-G levels in exposed patients (3.36 ± 5.12 ng/ml) in comparison with unexposed subjects (2.01 ± 2.84 ng/ml). The HLA-G 3'UTR 14 bp INS/DEL polymorphism correlated with sHLA-G, with the 14 bp INS/INS genotype associated with higher sHLA-G levels during the 12 months follow-up in unexposed subjects (p = 0.008). In conclusion, these results support a correlation between sHLA-G levels, genetics and HF disease in presence of work chemical exposition.


Assuntos
Antígenos HLA-G/sangue , Insuficiência Cardíaca/sangue , Exposição Ocupacional/análise , Regiões 3' não Traduzidas , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Estudos de Coortes , Feminino , Estudos de Associação Genética , Genótipo , Antígenos HLA-G/genética , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/estatística & dados numéricos , Polimorfismo Genético
7.
Sci Rep ; 9(1): 20158, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882973

RESUMO

Chronic obstructive pulmonary disease (COPD) is induced by cigarette smoking and characterized by inflammation of airway tissue. Since smokers with COPD have a higher risk of developing lung cancer than those without, we hypothesized that they carry more mutations in affected tissue. We called somatic mutations in airway brush samples from medium-coverage whole genome sequencing data from healthy never and ex-smokers (n = 8), as well as from ex-smokers with variable degrees of COPD (n = 4). Owing to the limited concordance of resulting calls between the applied tools we built a consensus, a strategy that was validated with high accuracy for cancer data. However, consensus calls showed little promise of representing true positives due to low mappability of corresponding sequence reads and high overlap with positions harbouring known genetic polymorphisms. A targeted re-sequencing approach suggested that only few mutations would survive stringent verification testing and that our data did not allow the inference of any difference in the mutational load of bronchial brush samples between former smoking COPD cases and controls. High polyclonality in airway brush samples renders medium-depth sequencing insufficient to provide the resolution to detect somatic mutations. Deep sequencing data of airway biopsies are needed to tackle the question.


Assuntos
Biomarcadores , Estudos de Associação Genética , Predisposição Genética para Doença , Pulmão/metabolismo , Pulmão/patologia , Mutação , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/etiologia , Idoso , Biópsia , Fumar Cigarros/efeitos adversos , Biologia Computacional , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Testes de Função Respiratória , Fatores de Risco , Índice de Gravidade de Doença , Sequenciamento Completo do Genoma
8.
BMC Pulm Med ; 19(1): 170, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488107

RESUMO

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is an aggressive interstitial lung disease with an unpredictable course. Occupational dust exposure may contribute to IPF onset, but its impact on antifibrotic treatment and disease prognosis is still unknown. We evaluated clinical characteristics, respiratory function and prognostic predictors at diagnosis and at 12 month treatment of pirfenidone or nintedanib in IPF patients according to occupational dust exposure. METHODS: A total of 115 IPF patients were recruited. At diagnosis, we collected demographic, clinical characteristics, occupational history. Pulmonary function tests were performed and two prognostic indices [Gender, Age, Physiology (GAP) and Composite Physiologic Index (CPI)] calculated, both at diagnosis and after the 12 month treatment. The date of long-term oxygen therapy (LTOT) initiation was recorded during the entire follow-up (mean = 37.85, range 12-60 months). RESULTS: At baseline, patients exposed to occupational dust [≥ 10 years (n = 62)] showed a lower percentage of graduates (19.3% vs 54.7%; p = 0.04) and a higher percentage of asbestos exposure (46.8% vs 18.9%; p 0.002) than patients not exposed [< 10 years (n = 53)]. Both at diagnosis and after 12 months of antifibrotics, no significant differences for respiratory function and prognostic predictors were found. The multivariate analysis confirmed that occupational dust exposure did not affect neither FVC and DLCO after 12 month therapy nor the timing of LTOT initiation. CONCLUSION: Occupational dust exposure lasting 10 years or more does not seem to influence the therapeutic effects of antifibrotics and the prognostic predictors in patients with IPF.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Poeira , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/epidemiologia , Exposição Ocupacional , Idoso , Progressão da Doença , Feminino , Humanos , Indóis/uso terapêutico , Itália , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Prospectivos , Piridonas/uso terapêutico , Análise de Regressão , Testes de Função Respiratória , Resultado do Tratamento
9.
Biomed Res Int ; 2019: 8327629, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31111068

RESUMO

Sleep deprivation and the consequent circadian clock disruption has become an emergent health question being associated with premature aging and earlier chronic diseases onset. Night-shift work leads to circadian clock misalignment, which is linked to several age-related diseases. However, mechanisms of this association are not well understood. Aim of this study is to explore in night-shift workers early indicators of oxidative stress response and biological aging [oxidized/methylated DNA bases and leukocytes telomere length (LTL)] and late indicators of functional aging [lung function measurements (FEV1 and FVC)] in relation to personal evaluation of work capacity, measured by work ability index (WAI). One hundred fifty-five hospital workers were studied within the framework of a cross-sectional study. We collected physiological, pathological, and occupational history including pack-years, alcohol consumption, physical activity, and night shifts, together with blood and urine samples. Relationships were appraised by univariate and multivariate ordered-logistic regression models. We found that workers with good and excellent WAI present higher FEV1 (p< 0.01) and number of night-work shifts (p<0.05), but they reveal higher urinary levels of 8-oxoGua (p<0.01) and shorter LTL (p<0.05). We confirmed that higher work ability was prevalent among chronological younger workers (p<0.05), who have also a significant reduced number of diseases, particularly chronic (p<0.01) and musculoskeletal diseases (p<0.01). The new findings which stem from our work are that subjects with the highest work ability perception may have more demanding and burdensome tasks; they in fact present the highest number of night-shift work and produce unbalanced oxidative stress response that might induce premature aging.


Assuntos
Estresse Oxidativo , Fenômenos Fisiológicos Respiratórios , Telômero/metabolismo , Tolerância ao Trabalho Programado/fisiologia , Tolerância ao Trabalho Programado/psicologia , Adolescente , Adulto , Idoso , Envelhecimento/fisiologia , Pessoal Técnico de Saúde , Relógios Biológicos , Ritmo Circadiano/fisiologia , Estudos Transversais , Metilação de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Oxirredução , Análise de Regressão , Jornada de Trabalho em Turnos , Sono/fisiologia , Transtornos do Sono do Ritmo Circadiano/psicologia , Inquéritos e Questionários , Adulto Jovem
10.
Respiration ; 97(3): 223-233, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30205380

RESUMO

BACKGROUND: In elderly smokers, chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) usually present with dyspnoea. COPD and CHF are associated -almost invariably with concomitant chronic diseases, which contribute to severity and prognosis. OBJECTIVES: We investigated similarities and differences in the clinical presentation, concomitant chronic diseases and risk factors for -mortality and hospitalization at 3-year follow-up in elderly smokers/ex-smokers with a primary diagnosis of COPD or CHF recruited and followed in specialized centers. METHODS: We examined 144 patients with COPD and 96 with CHF, ≥65 years, ≥20 pack/years, and measured COPD Assessment Test (CAT) score, modified Medical Research Council, NYHA, and Charlson Index, routine blood test, estimated glomerular filtration rate, HRCT scan, 6-min walk test. In addition, in each patient we actively searched for CHF, COPD, peripheral vascular disease, and metabolic syndrome. RESULTS: COPD and CHF patients had mild to moderate disease, but the majority was symptomatic. Comorbidities were highly prevalent and often unrecognized in both groups. COPD and CHF patients had a similar risk of hospitalization and death at 3 years. Lower glomerular filtration rate, shorter 6MWT, and ascending aorta calcification score ≥2 were independent predictors of mortality in COPD, whereas previous 12 months hospitalizations, renal disease, and heart diameter were in CHF patients. Lower glomerular filtration rate value, higher CAT score, and lower FEV1/FVC ratio were associated with hospitalization in COPD, while age, lower FEV1% predicted, and peripheral vascular disease were in CHF. CONCLUSIONS: There are relevant similarities and differences between patients with COPD and CHF even when admitted to specialized outpatient centers, suggesting that these patients should be manage in multidisciplinary units.


Assuntos
Insuficiência Cardíaca/epidemiologia , Hospitalização/tendências , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fumar/efeitos adversos , Idoso , Comorbidade , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fumar/epidemiologia , Taxa de Sobrevida/tendências , Fatores de Tempo
11.
PLoS One ; 13(12): e0208842, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30543689

RESUMO

OBJECTIVES: Return to work after acute myocardial infarction (AMI), a leading cause of death globally, is a multidimensional process influenced by clinical, psychological, social and occupational factors, the single impact of which, however, is still not well defined. The objective of this study was to investigate these 4 factors on return to work (RTW) within 365 days after AMI in a homogeneous cohort of patients who had undergone an urgent coronary angioplasty. PARTICIPANTS: We studied 102 patients, in employment at the time of AMI (88.24% of men), admitted to the Department of Cardiology of the University-Hospital of Ferrara between March 2015 to December 2016. Demographical and clinical characteristics were obtained from the cardiological records. After completing an interview on social and occupational variables and the Hospital Anxiety and Depression (HADS) questionnaire, patients underwent exercise capacity measurement and spirometry. RESULTS: Of the 102 patients, only 12 (12.76%) held a university degree, 68.63% were employees and 31.37% self-employed. The median number of sick-leave days was 44 (IQR 33-88). At day 30, 78.5% of all subjects had not returned to work, at day 60, 40.8% and at day 365 only 7.3% had not resumed working. At univariate analyses, educational degree (p = 0.026), self-employment status (p = 0.0005), white collar professional category (p = 0.020) and HADS depression score were significant for earlier return to work. The multivariate analysis confirms that having a university degree, being self-employed and presenting a lower value of HADS depression score increase the probability of a quicker return to work. CONCLUSIONS: These findings suggest that the strongest predictors of returning to work within 1 year after discharge for an acute myocardial infarction are related more to socio-occupational than to clinical parameters.


Assuntos
Angioplastia Coronária com Balão , Infarto do Miocárdio/cirurgia , Retorno ao Trabalho , Adulto , Depressão/psicologia , Emprego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Licença Médica , Fatores Socioeconômicos , Fatores de Tempo
12.
Multidiscip Respir Med ; 13: 35, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30305900

RESUMO

Chronic obstructive pulmonary disease (COPD) is a common comorbidity of heart failure (HF), but remains often undiagnosed, and we aimed to identify symptoms predicting COPD in HF. As part of an observational, prospective study, we investigated stable smokers with a confirmed diagnosis of HF, using the 8-item COPD-Assessment-Test (CAT) questionnaire to assess symptoms. All the items were correlated with the presence of COPD, and logistic regression models were used to identify independent predictors. 96 HF patients were included, aged 74, 33% with COPD. Patients with HF and COPD were more symptomatic, but only breathlessness when walking up a hill was an independent predictor of COPD (odds ratio = 1.33, p = 0.0484). Interestingly, COPD-specific symptoms such as cough and phlegm were not significant. Thus, in elderly smokers with stable HF, significant breathlessness when walking up a hill is most indicative of associated COPD, and may indicate the need for further lung function evaluation.

13.
PLoS One ; 13(7): e0201045, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30024962

RESUMO

Whether the association of work disability with obstructive sleep apnea (OSA) is mainly due to the disease, i.e. the number and frequency of apneas-hypoapneas, or to coexisting factors independent from the disease, is not well-established. In this study, we aim to evaluate work ability in a group of subjects undergoing OSA workup and to identify the major contributors of impaired work ability. In a cross-sectional study, we enrolled 146 consecutive subjects who have been working for the last five years and referred to the sleep disorders outpatients' clinic of the University-Hospital of Ferrara, Italy, with suspected OSA. After completing an interview in which the Work Ability Index (WAI) and the Epworth Sleepiness Scale (ESS) questionnaires were administered to assess work ability and excessive daytime sleepiness, respectively, subjects underwent overnight polysomnography for OSA diagnosing and spirometry. Of the 146 subjects, 140 (96%) completed the tests and questionnaires and, of these, 66 exhibited work disability (WAI < 37). OSA was diagnosed (apnea-hypopnea index ≥ 5) in 45 (68%) of the 66 subjects. After controlling for confounders, a lower level of forced expiratory volume at 1 second (FEV1), [odds ratio 0.97 (95% CI 0.95-1.00)], older age [1.09 (95% CI 1.03-1.15)], excessive daytime sleepiness [3.16 (95% CI 1.20-8.34)] and a worse quality of life [0.96 (95% CI 0.94-1.00)], but not OSA [1.04 (95% CI 0.41-2.62)], were associated with work disability. Patients with a higher number of diseases, in which OSA was not included, and a lower quality of life had an increased probability of absenteeism in the previous 12 months. In subjects with suspected OSA, FEV1 can be an important predictor of work disability.


Assuntos
Absenteísmo , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Volume Expiratório Forçado , Qualidade de Vida , Apneia Obstrutiva do Sono/complicações , Estudos Transversais , Distúrbios do Sono por Sonolência Excessiva/etiologia , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Polissonografia , Fatores de Risco , Inquéritos e Questionários
14.
Int Arch Occup Environ Health ; 91(6): 735-744, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29858653

RESUMO

OBJECTIVES: Laboratory animal allergy is a highly prevalent occupational disease among exposed workers. The aim of the study was to validate the biomarkers of airway inflammation in laboratory animal (LA) care workers. METHODS: All of the participants in this observational study (63 LA care workers and 64 controls) were administered a clinical questionnaire, underwent spirometry and a skin prick or radioallergosorbent test for common and occupational aeroallergens, and the fraction of exhaled nitric oxide (FeNO50), exhaled breath condensate hydrogen peroxide (EBC H2O2) and serum pneumoprotein levels were measured. Multivariate analysis (ANCOVA) was used to assess the interactions of the variables. RESULTS: FeNO50 levels correlated with exposure (p = 0.002), sensitisation (p = 0.000) and age (p = 0.001), but there was no interaction between exposure and sensitisation when age was considered in the model (p = 0.146). EBC-H2O2 levels were higher in the sensitised workers than in the sensitised controls [0.14 (0.08-0.29) µM vs 0.07 (0.05-0.12) µM; p < 0.05]. Serum surfactant protein A (SP-A) levels were unaffected by exposure, sensitisation or age, although higher levels were observed in symptomatic workers; however, SP-D levels were influenced by exposure (p = 0.024) and age (p = 0.022), and club cell 16 levels were influenced by sensitisation (p = 0.027) and age (p = 0.019). CONCLUSIONS: The presence of the clinical symptoms associated with LA exposure and high FeNO levels should prompt further medical assessments in LA workers. Although EBC-H2O2 levels do not seem to reflect eosinophilic inflammation, serum SP-A levels could be used to monitor progression from rhinitis to asthma.


Assuntos
Animais de Laboratório , Biomarcadores/análise , Exposição Ocupacional/efeitos adversos , Rinite Alérgica/etiologia , Rinite Alérgica/fisiopatologia , Adulto , Idoso , Análise de Variância , Animais , Estudos de Casos e Controles , Feminino , Humanos , Peróxido de Hidrogênio/análise , Hipersensibilidade/etiologia , Hipersensibilidade/fisiopatologia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/análise , Proteína A Associada a Surfactante Pulmonar/sangue , Proteína D Associada a Surfactante Pulmonar/sangue , Teste de Radioalergoadsorção , Espirometria , Inquéritos e Questionários , Adulto Jovem
15.
PLoS One ; 12(7): e0180859, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28704452

RESUMO

BACKGROUND: Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented. However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited. METHODS: Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons. RESULTS: We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes) was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group) (PC1, Padj = 0.002). Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects. No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA. Co-occurrence analysis suggests the presence of networks of co-occurring bacteria. Four communities of positively correlated bacteria were revealed. The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype. CONCLUSION: Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells. This might result in a changed interplay with the host immune system.


Assuntos
Bactérias/classificação , Pulmão/microbiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Análise de Sequência de DNA/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Bactérias/genética , Bactérias/isolamento & purificação , Código de Barras de DNA Taxonômico/métodos , DNA Bacteriano/genética , DNA Ribossômico/genética , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Microbiota , Pessoa de Meia-Idade , Prevotella/classificação , Prevotella/genética , Prevotella/isolamento & purificação , Doença Pulmonar Obstrutiva Crônica/complicações , RNA Ribossômico 16S/genética , Streptococcus/classificação , Streptococcus/genética , Streptococcus/isolamento & purificação
16.
Front Immunol ; 8: 516, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28536575

RESUMO

Aging is an emerging worldwide threat to public health, even in the workplace, as it links with risk of illness and death. Bewildered inflammatory responses and stressful conditions associate with age-related disorders. Additionally, circadian rhythm disruption, a critical health issue in night-shift workers, correlates with premature aging. We investigated the hypothesis of a link between altered inflammatory response, detected by plasmatic long pentraxin 3 (PTX3), and biological aging, measured by leukocyte telomere length (LTL), attrition, and possibly induced by night-shift work. Within the framework of a cross-sectional study, such possible relationships were appraised by simultaneous equation model (SEM) technique among day and night-shift hospital workers. PTX3 levels, modulated by several aging conditions [i.e., body mass index (BMI) (beta = -0.22; p = 0.022), C-reactive protein (CRP) (beta = -0.07; p = 0.000), and cardiovascular diseases with hypertension included (CVD) (beta = -0.12; p = 0.000)], positively associate with LTL (coefficient = 0.15; p = 0.033). LTL, in turn is reduced by CVD (beta = -0.15; p = 0.000), binge drinking (beta = -0.10; p = 0.004), and CRP (beta = -0.05; p = 0.026). On the other hand, night-shift work, found to be remarkably free from aging risk factors [i.e., age (beta = -0.13; p = 0.017), BMI (beta = -0.17; p = 0.030), CVD (beta = -0.14; p = 0.000), and binge drinking (beta = -0.13; p = 0.000)], does associate almost significantly with reversed PTX3 (coefficient = -0.09; p = 0.089) and even with CRP (beta = 0.17; p = 0.000). In conclusion, the SEM analysis indicates that PTX3 is positively linked to LTL. The finding suggests a possible new role of this long pentraxin that, by orchestrating an efficient governance of inflammatory processes, may protect telomere from attrition, ensuring therefore the genetic stability of cells. The higher CRP levels among night-shift workers suggest that night-shift work is associated with increased systemic inflammation. This would make nocturnal workers more susceptible to premature aging.

17.
Ig Sanita Pubbl ; 73(6): 633-648, 2017.
Artigo em Italiano | MEDLINE | ID: mdl-29573389

RESUMO

The hospital as a work environment is particularly characterized by various risks for healthcare workers (HCWs). The main risk is represented by biological accidents, associated with the parenteral transmission of pathogens. Biological injuries can occur during the care service and the manipulation of biological fluids. Hepatitis B (and hepatitis D), hepatitis C and HIV are the most common infections transmitted by biological injuries. Physicians should acquire awareness of the risks associated with their professional activity during their training as medical residents (MRs). Some infectious diseases are preventable by vaccination and the "National Immunization Plan 2017-2019" (PNPV) recommends HCWs vaccination against hepatitis B, influenza, measles -mumps -rubella, chicken pox, and pertussis. Besides, not only HCWs' vaccination can prevent the disease in healthcare professionals, but it also may reduce the transmission to patients. Therefore, active immunization of HCWs by recommended vaccinations plays an important role to prevent disease cases, complications and death in patients. An increased awareness of risk behaviors is the first important point to address in order to reduce biological accidents and infectious diseases transmission, so as to reduce their frequency. Besides, HCWs' vaccination is useful to reinforce protection and to prevent the transmission of some infectious diseases in case of exposure. The aim of this five-year incidence study is to investigate the MRs' biological accidents characteristics and to analyze the MRs' immune status at the University of Ferrara in the period 2011-2015. Data on MRs' biological accidents and immune status at Azienda Ospedaliero-Universitaria of Ferrara in 2011-2015 were analyzed by Microsoft Excel 2007 Software. In this study, the percentage of MRs' biological injuries compared to the total number of MRs showed an annual variability, with a peak in 2011 (11.9%). During the analyzed period, there were 190 biological injuries among the MRs: 81% were percutaneous injuries and blood was the biological fluid involved in 86.3% of cases. The most frequent lesion was puncture (62.6%), occurred in 41.1% of cases by suture needles; 46.3% of accidents occurred in the operating block. These data can be explained by the more invasive and at risk activities carried out in these Operative Units. The high injuries percentage in MRs may be related to less work experience and inadequate training or informations about personal protective equipment use. Among MRs, 93.7%, 93.3% and 96.6% were immune to measles, chicken pox and hepatitis B, respectively; only in the case of rubella, 11.9% of MRs was not immune. This research showed, accordingly to published data, high adhesion to hepatitis B vaccination. However, the healthcare workers' vaccine coverage is still sub-optimal; active immunization by recommended vaccines should be implemented for both parenteral and airborne diseases. As a matter of fact, the recent measles outbreak has involved healthcare workers (4689 cases of measles, 305 in HCWs). Finally, the General Directorates of Health-care settings should improve healthcare personnel adhesion to vaccinations, such as influenza, by promotion activities in the workplace. A proposal in order to achieve coverage objectives could be making vaccinations mandatory, as well as already implemented in other countries.


Assuntos
Acidentes de Trabalho/estatística & dados numéricos , Derramamento de Material Biológico/estatística & dados numéricos , Controle de Doenças Transmissíveis , Imunização , Internato e Residência , Vacinas , Hospitais Universitários , Humanos , Incidência , Itália , Ferimentos Penetrantes Produzidos por Agulha/epidemiologia , Fatores de Tempo
18.
Oncotarget ; 7(50): 82700-82711, 2016 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-27716620

RESUMO

Malignant pleural mesothelioma (MPM), a fatal cancer, is an occupational disease mostly affecting workers ex-exposed to asbestos fibers. The asbestos, a cancerogenic mineral of different chemical composition, was widely employed in western Countries in industrial manufactures of different types. MPM may arise after a long latency period, up to five decades. MPM is resistant to conventional chemo- and radio-therapies. Altogether, these data indicate that the identification of new and specific markers are of a paramount importance for an early diagnosis and treatment of MPM. In recent years, microRNAs expression was found dysregulated in patients, both in cancer cells and sera, affected by tumors of different histotypes, including MPM. Cell and circulanting microRNAs, found to be dysregulated in this neoplasia, were proposed as new biomarkers. It has been reported that circulating microRNAs are stable in biological fluids and could be employed as potential MPM biomarkers. In this investigation, circulating microRNAs (miR) from serum samples of MPM patients and workers ex-exposed to asbestos fibers (WEA) and healthy subjects (HS) were comparatively analyzed by microarray and RT-qPCR technologies. Our results allowed (i) to select MiR-3665, an endogenous stable microRNA, as the internal control to quantify in our analyses circulating miRNAs; to detect (ii) miR-197-3p, miR-1281 and miR 32-3p up-regulated in MPM compared to HS; (iii) miR-197-3p and miR-32-3p up-regulated in MPM compared to WEA; (iv) miR-1281 up-regulated in both MPM and WEA compared to HS. In conclusion, three circulating up-regulated microRNAs, i.e. miR-197-3p, miR-1281 and miR-32-3p are proposed as potential new MPM biomarkers.


Assuntos
Amianto/efeitos adversos , Biomarcadores Tumorais/sangue , MicroRNA Circulante/sangue , Neoplasias Pulmonares/sangue , Mesotelioma/sangue , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Neoplasias Pleurais/sangue , Área Sob a Curva , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , MicroRNA Circulante/genética , Perfilação da Expressão Gênica/métodos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mesotelioma/genética , Mesotelioma/patologia , Mesotelioma Maligno , MicroRNAs/sangue , MicroRNAs/genética , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Valor Preditivo dos Testes , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Eur Respir J ; 48(1): 92-103, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27230444

RESUMO

EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting "emphysema-dominant", "airway disease-dominant", "mixed" disease and "mild" disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2 ) and carbon dioxide (PCO2 ) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group.The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease.


Assuntos
Fenótipo , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/normas , Adulto , Idoso , Europa (Continente) , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Respiratório/fisiopatologia , Espirometria
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