Associations between sarcoidosis clinical course and ANXA11 rs1049550 C/T, BTNL2 rs2076530 G/A, and HLA class I and II alleles.

BACKGROUND: A genetic background may be responsible for the different clinical courses in sarcoidosis. We analyzed associations between sarcoidosis clinical course and HLA class I/II alleles and susceptibility gene SNPs ANXA11 rs1049550 C/T and BTNL2 rs2076530 G/A in a Portuguese population, investigating possible gene-gene interactions. METHODS: We studied 138 unrelated Caucasian sarcoidosis patients (78 women, 56.5%; mean age, 37.2 ± 12.1 years). Disease that persisted after 2 years was considered chronic. Samples were genotyped for ANXA11 rs1049550 C/T and BTNL2 rs2076530 G/A SNPs using TaqMan Real-Time PCR Assays. HLA class I/II alleles were typed using PCR sequence-specific primers. RESULTS: Sixty-six patients experienced disease resolution and 72 (52%) developed chronic disease. Comparison of rs1049550 and rs2076530 allele frequencies showed no significant differences. Only the HLA DRB1*03 allele was significantly associated with disease resolution (21.2% vs 4.9% for chronic disease; RR = 0.35; P < .01 after Bonferroni correction). In the logistic regression models evaluating the association between HLA alleles and chronic sarcoidosis adjusted for rs1049550 and rs2076530, only DRB1*03 was significantly associated with disease resolution. No significant interactions were found in any of the logistic regression analyses. CONCLUSIONS: In this population of Caucasian patients with sarcoidosis, only DRB1*03 was associated with disease resolution after 2 years' follow-up, with no significant interactions found for susceptibility gene SNPs ANXA11 rs1049550 or BTNL2 rs2076530.

Serum metalloproteinases 1 and 7 in the diagnosis of idiopathic pulmonary fibrosis and other interstitial pneumonias.

INTRODUCTION: Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) has important therapeutic and prognostic implications and would be greatly aided by reliable diagnostic biomarkers as IPF has sometimes overlapping features with other interstitial lung diseases (ILD). OBJECTIVES: To explore the value of serum metalloproteinases (MMP) 1 and 7 levels in the differential diagnosis of IPF with other ILD. METHODS: MMP-1/7 serum levels were measured using Luminex xMAP technology in 139 patients- 47 IPF, 36 non-IPF Usual Interstitial Pneumonia (UIP), 14 idiopathic Nonspecific Interstitial Pneumonia (iNSIP), 29 secondary NSIP (secNSIP), 13 stage IV sarcoidosis- and 20 healthy controls, and compared using the Mann-Whitney U test. RESULTS: MMP-1 was significantly higher in IPF than non-IPF UIP (P = .042) and sarcoidosis (P = .027). MMP-7 was significantly higher in IPF than controls (P < .001), non-IPF UIP (P = .003), secNSIP (P < .001), and sarcoidosis (P < .001). The Area Under the Curve for IPF versus other ILD was 0.63 (95%CI, 0.53-0.73) for MMP-1, 0.73 (95%CI, 0.65-0.81) for MMP-7, and 0.74 (95%CI, 0.66-0.82) for MMP-1/MMP-7 combined. Sensitivity and specificity for MMP-7 cutoff = 3.91 ng/mL was 72.3% and 66.3%, respectively, Positive Predictive Values = 52.3% and Negative Predictive Values = 82.4%. CONCLUSIONS: MMP-1 and particularly MMP-7 serum levels were significantly higher in IPF than in non-IPF UIP, the main entity in differential diagnosis. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF diagnosis needs to be considered and further explored.

Circulating Ang-2 mRNA expression levels: looking ahead to a new prognostic factor for NSCLC [corrected].

Non-small cell lung cancer (NSCLC) is the most common cancer and the leading cause of death from cancer worldwide. Antiangiogenic strategies directed towards tumor stroma are becoming gold standard in NSCLC treatment and researchers have been searching for biomarkers to identify patients for whom therapy with antiangiogenic inhibitors may be most beneficial and the importance of these as prognostic factors in NSCLC. The purpose of this study was to evaluate the prognostic value of circulating Ang-2 mRNA levels prior to treatment in NSCLC patients. The mRNA levels were determined by quantitative real-time PCR in the peripheral blood of 92 NSCLC patients. Our results demonstrate that patients with high circulating Ang-2 mRNA levels have diminished overall survival when compared to those with low mRNA levels (20.3 months vs 34.3 months, respectively; Log Rank Test, p = 0.016), when considering all NSCLC stages and this difference is even bigger when considering only patients with stage IV (15.9 months vs 31.3 months, respectively; Log Rank Test, p = 0.036). Moreover, circulating Ang-2 mRNA levels independently determine overall survival, and the concordance (c) index analysis showed that the definition of a nomogram that contains information regarding tumor stage, patients' smoking status and circulating Ang-2 mRNA levels present an increased capacity to predict overall survival in NSCLC patients (c-index 0.798). These results suggest that this nomogram could serve as a unique and practical tool to determine prognosis in NSCLC, not relying on the availability of adequate surgical or biopsy specimens of NSCLC. Attending to our results, the circulating Ang-2 mRNA levels should also be included in the design of preclinical studies and clinical trials involving antiangiogenic drugs targeting Ang-2, to guide adequate patient stratification and dose selection and increasing the likelihood of benefit to a level that is acceptable to patients and clinicians.

Neoplastic severe central airways obstruction, interventional bronchoscopy: a decision-making analysis.

OBJECTIVE: Cancer can involve the airways, causing various degrees of obstruction. Usually, after days or months of mild to moderate undervalued symptoms, severe dyspnea arises abruptly, imposing an immediate attempt to restore the airflow regardless of the etiology. This study focuses on the development of a predictive preintervention model that is useful when deciding whether to perform therapeutic interventional bronchoscopy in patients with severe central airway obstruction. METHODS: A total of 804 patients who underwent rigid bronchoscopy under general anesthesia to treat severe neoplastic central airway obstruction from 1990 to 2009 were studied. Electronic records for patients who underwent bronchoscopy were analyzed. The patients were primarily male (n = 618, 76.9%) and the median age was 62 years. Lung cancer was the most frequent cause of neoplastic airway obstruction (n = 645, 81.65%). An estimate of the probability of individual endoscopic success was made. RESULTS: Of the 804 patients with severe neoplastic airway obstruction, 681 (84.7%) achieved luminal clearance, and the procedure was considered an endoscopic success. Tracheal involvement (rate ratio, 1.21; range, 1.16-1.27) endoluminal mass (rate ratio, 1.13; range, 1.06-1.12), and extrinsic compression (rate ratio, 1.17; 1.11-1.17) were associated significantly with a favorable endoscopic outcome. Tumor location and any kind of mucosal infiltration were the main determinants of the predictive preoperative model of intervention success. CONCLUSIONS: Endoscopic characteristics and location of the neoplastic lesions are the major determinants of patients' endoscopic outcome. The preintervention model adds to the clinical evaluation an important contribution to the decision-making process on performing therapeutic interventional bronchoscopy in a critical setting.

Hyperbaric oxygen therapy treatment for the recovery of muscle injury induced in rats.

INTRODUCTION: We evaluated the effect of hyperbaric oxygen treatment (HBOT) in the recovery of muscle injury in rats. MATERIALS AND METHODS: Twelve female Wistar rats, weighing 200-250 g, were submitted to contusion of the right gastrocnemius muscle. Animals were then randomly assigned to an untreated control group or an HBOT-treated group. The HBOT group was given three, 60-minute sessions of HBOT at 253 kPa pressure at 24, 48 and 72 hours post injury. After the last session all animals were sacrificed and both gastrocnemius muscles removed, the left muscle as an internal control. Blood samples were taken for creatine phosphokinase (CPK). Using a standard traction technique, the muscles were analysed for their biomechanical properties: hardness, maximum elongation and maximum weight. RESULTS: Significant differences were found between uninjured and injured muscles and between untreated and HBOT groups in maximum weight and hardness: maximum weight in the non-treated group 18.27 ± 2.99 N versus 26.18 ± 2.84 N in the HBOT group (P = 0.007); hardness in the non-treated group 2.24 ± 0.38 103 N m⁻¹ versus 3.19 ± 0.32 10³ N m⁻¹ in the HBOT group (P = 0.001). The difference in maximum elongation was not significant (P = 0.793). CPK was significantly different between the two groups (non-treated 6,445 ± 387 i.u. L⁻¹; HBOT 4,551 ± 80 i.u. L⁻¹; P = 0.009). CONCLUSIONS: HBOT seems to play a positive role in the recovery of induced muscle injury in rats. However relevant, these results cannot be extrapolated to humans, for whom further clinical studies are warranted.

BTNL2 gene polymorphism associations with susceptibility and phenotype expression in sarcoidosis.

A functional polymorphism within butyrophilin-like 2 (BTNL2) gene has been described as a potential risk factor for sarcoidosis. The association between chronicity and the rs2076530 SNP A allele has also been reported. This study evaluates the BTNL2 rs2076530 G/A allele associations with sarcoidosis susceptibility and disease evolution in a Portuguese cohort of patients. A case-control study of 151 patients and 150 controls was performed. Allele frequencies were compared with Chi-square test in a univariate analysis and with logistic regression in a multivariate analysis. BTNL2 rs206530 A allele frequencies were significantly higher in sarcoidosis with no linkage disequilibrium with HLA-DRB1 alleles, except in the subgroup of patients with Löfgren syndrome where the determinant allele was HLA-DRB1*03. The A allele was also increased in those with isolated thoracic disease, with no differences regarding radiological stages or disease evolution. HLA-DRB1*03, besides the association with Löfgren syndrome was significantly related with disease resolution. Our data confirms the association of BTNL2 rs2076530 A allele with sarcoidosis susceptibility in a Portuguese population. We found independent genetic risk factors in clinically distinct disease phenotypes: BTNL2 rs2076530 A allele in patients without Löfgren syndrome or with isolated thoracic disease, and HLA-DRB1*03 in Löfgren syndrome or disease resolution.

Indoor air pollution on nurseries and primary schools: impact on childhood asthma--study protocol.

BACKGROUND: Several studies have demonstrated an association between the exposure to indoor air pollution (IAP) and childhood asthma. Evidence is suggesting that several air pollutants may contribute to both exacerbation and development of asthma, but some uncertainty remains concerning the specific causative role of IAP. This paper reports an epidemiologic study aiming to reduce the existing lacks on the association between long-term exposure to pollution mixtures and the development and exacerbation of childhood asthma. METHODS/DESIGN: Based on the implementation of the study in 8 nurseries and 8 primary schools, from which, 2 nurseries and 2 primary schools in sites influenced by traffic and other 2 nurseries and 2 primary schools in background sites at urban and rural areas, the study will analyse the exposure to both urban and rural pollution as well as to traffic emissions (some homes of the children will be included in the study). Furthermore, based on the answers to validated questionnaires (as those used in the International Study of Asthma and Allergies in Childhood - ISAAC) filled in by the parents and on medical exams, the study will assess the prevalence, incidence and exacerbation of asthma, thus considering both short and long-term effects. The approximate number of children in the study will never be less than 600, guaranteeing 80% of study power (significant at a 5% level). DISCUSSION: This study intends to contribute for the understanding of the role of environmental factors, namely indoor air pollution, on asthma considering a risk group of different ages, and for the development of preventive measures, which are considered priority issues by the European Commission, according to the European Environmental Agency and the World Health Organization.

Pneumococcal polysaccharide vaccination for adults: new perspectives for Europe.

Vaccination is the only public-health measure likely to reduce the burden of pneumococcal diseases. In 2010, a group of European experts reviewed evidence on the burden of pneumococcal disease and the immunogenicity, clinical effectiveness and cost-effectiveness of vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23). They also considered issues affecting the future use of PPV23 and pneumococcal conjugate vaccines in the elderly and adults at high risk of pneumococcal disease. PPV23 covers 80-90% of the serotypes responsible for invasive pneumococcal disease in Europe. Primary vaccination and revaccination with PPV23 are well tolerated, induce robust, long-lasting immune responses in elderly adults and are cost effective. Ensuring protection against pneumococcal disease requires monitoring of the changing epidemiology of pneumococcal serotypes causing invasive pneumococcal disease and improving vaccine coverage. In the future, it will be critically important for pneumococcal vaccination recommendations for elderly adults to be based on comparative evaluations of PPV23 and newer pneumococcal conjugate vaccines with regard to their long-term immunogenicity, clinical effectiveness and cost-effectiveness.

Prevalence of asthma and rhinitis in 13 year old adolescents in Porto, Portugal.

BACKGROUND: The prevalence of asthma and rhinitis has been increasing over the past few decades, but the last few years have seen these rates stabilise or even decrease. AIM: The aim of our study was to describe the prevalence of rhinitis, asthma or asthma-like symptoms in 13 year-old urban adolescents. METHODS: Eligible participants were all students at state and private schools in Porto born in 1990. 2161 (77.5%) agreed to participate. Information was obtained using self-administered questionnaires inquiring into social, demographic, behavioural and clinical history including asthma and allergic diseases in the adolescent and the family. We used the Portuguese version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and we also performed spirometry tests. RESULTS: In this sample of 13 year old urban adolescents the prevalence of asthma ever was 12.9%, 84.4% with physician diagnosis. Lifetime wheezing was reported by 18.3% and current wheezing by 9.3% of the adolescents. Rhinitis was referred to by 10.1%, but the prevalence of adolescents with sneezing ever, or a runny/blocked nose, was 32.0% and the prevalence in the last 12 months was 27.4%. CONCLUSION: We concluded that there was stabilisation or even decrease in the prevalence of asthma and rhinitis symptoms and diagnosis in adolescents reported in Porto, compared with the 2002 ISAAC study, as observed in other surveys in Europe. Asthma and rhinitis is frequently present in the same patient and nocturnal cough is an important symptom concomitant with nasal symptoms. Measures of lung function permitted the discrimination of adolescents with respiratory complaints.

[Suberosis and bird fancier's disease: comparative study of radiological, functional and bronchoalveolar characteristics profile]. / Suberose e doença dos criadores de aves: estudo comparativo do perfil radiológico, funcional e do lavado broncoalveolar.

Extrinsic Allergic Alveolitis (EAA) is an immunologically mediated interstitial lung disease that may result from repeated inhalation of many different environmental agents. Heterogeneity of the clinical presentation and bronchoalveolar lavage profiles has been described, possibly related to different occupational exposures. The aim of our study was to compare bronchoalveolar lavage fluid (BALF), clinical, functional and radiological characteristics of the two most frequent forms of EAA seen in our practice: Suberosis and Bird Fancier's Disease (BFD). We included 81 patients with Suberosis, with a mean age of 38.8+/-11.3 years and a mean exposure of 20.0 +/- 10.5 years and 32 patients with BFD, with a mean age of 46.3+/-11.8 years and mean exposure of 10.5 +/- 1.0 years. Patients with BFD had more acute forms, while subacute and chronic presentations predominated in Suberosis. Restrictive defect was the most frequent pattern of lung function impairment, and more severe in BFD. Ground glass opacities were the most frequent pattern in high-resolution computed tomography. A normal chest x-ray was more frequently seen in Suberosis. Both types of EAA had lymphocytic alveolitis in BALF: Suberosis - 6.6 +/- 5.7 x 105 ml-1 cells, 58.8 +/- 18.9% lymphocytes; bird fancier's disease - 9.0 +/- 6.5 x 105 ml-1 cells, 61.7 +/- 22.2% lymphocytes. Although BALF CD8+ lymphocytes predominated in both diseases, the proportion of CD4+ and CD4/CD8 ratios were significantly higher in Bird Fancier's Disease (Suberosis: 0.47 +/- 0.33 versus BFD: 1.1 +/- 1.5; p <0.005). Moreover, BALF cellularity and mast cell counts were also significantly higher in BFD. In conclusion, Suberosis and bird fancier's disease are EAA with different clinical and laboratory profiles, suggesting that despite their pathophysiological similarities, different antigenic exposures may cause different immune and inflammatory response dynamics in the lung.

Um estudo sobre a dispersäo de casos de malária no Brasil / Dispersion of cases of malaria in Brazil

Resultados de cinquenta e três mil investigaçöes de casos de malária, realizadas pela SUCAM em todas as regiöes brasileiras, durante o ano de 1985, permitiram identificar os polos de dispersäo e de recepçäo de portadores de plasmódios. Determinou-se as áreas de influência de três municípios com alta transmissäo: S. Félix do Xingu (PA), Colíder (MT) e Ariquemes (RO), que se estendem por todo o país. Confirma-se a existência de forte pressäo de casos de malária da Amazônia para as demais regiöes, o que tende a introduzir a endemia nessas regiöes a partir do surgimento de focos novos ativos. Conclui-se que a reduçäo da transmissäo nos polos de dispersäo mais importantes levará a diminuiçäo dessa pressäo e do número global de casos de endemia no país