Assessment of vitamin A status in chronic obstructive pulmonary disease patients and healthy smokers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cytokines and dietary energy restriction in stable chronic obstructive pulmonary disease patients

Tumour necrosis factor (TNF)-α has been found to be increased in malnourished chronic obstructive pulmonary disease (COPD) patients; however, the main cause of this phenomenon remains undetermined. In normal subjects, TNF-α production may be induced by dietary energy deprivation. The aim of this study was to investigate if stable COPD patients present alterations of inflammatory mediators after 48 h of dietary energy restriction. Fourteen COPD patients were admitted to the hospital while receiving an experimental diet with an energy content of approximately one-third of their energy needs. Clinical evaluation, nutritional assessment and serum levels of interleukin (IL)-6, TNF-α and C-reactive protein, and secretion of TNF-α by peripheral blood monocytes were assessed on admission and after the experimental diet. For reference values of the laboratory parameters, blood was collected from 10 healthy, elderly subjects. COPD patients showed significantly higher serum concentrations of IL-6 than control subjects, however, the experimental diet was not associated with statistically significant changes in the inflammatory mediators. The findings of this study, although preliminary because of the limited degree and duration of the energy restriction, suggest that the elevated levels of tumour necrosis factor-α, previously described in undernourished or weight-losing chronic obstructive pulmonary disease patients, may not be linked to a decrease of dietary energy intake.

Respiratory chemoreceptor function in vertebrates - Comparative and evolutionary aspects

The sensing of blood gas tensions and/or pH is an evolutionarily conserved, homeostatic mechanism, observable in almost all species studied from invertebrates to man. In vertebrates, a shift from the peripheral O2-oriented sensing in fish, to the central CO2/pH sensing in most tetrapods reflects the specific behavioral requirements of these two groups whereby, in teleost fish, a highly O2-oriented control of breathing matches the ever-changing and low oxygen levels in water, whilst the transition to air-breathing increased the importance of acid-base regulation and O2-related drive, although retained, became relatively less important. The South American lungfish and tetrapods are probably sister groups, a conclusion backed up by many similar features of respiratory control. For example, the relative roles of peripheral and central chemoreceptors are present both in the lungfish and in land vertebrates. In both groups, the central CO2/pH receptors dominate the ventilatory response to hypercarbia (60-80), while the peripheral CO2/pH receptors account for 20-30. Some basic components of respiratory control have changed little during evolution. This review presents studies that reflect the current trends in the field of chemoreceptor function, and several laboratories are involved. An exhaustive review on the previous literature, however, is beyond the intended scope of the article. Rather, we present examples of current trends in respiratory function in vertebrates, ranging from fish to humans, and focus on both O2 sensing and CO2 sensing. As well, we consider the impact of chronic levels of hypoxia - a physiological condition in fish and in land vertebrates resident at high elevations or suffering from one of the many cardiorespiratory disease states that predispose an animal to impaired ventilation or cardiac output. This provides a basis for a comparative physiology that is informative about the evolution of respiratory functions in vertebrates and about human disease. Currently, most detail is known for mammals, for which molecular biology and respiratory physiology have combined in the discovery of the mechanisms underlying the responses of respiratory chemoreceptors. Our review includes new data on nonmammalian vertebrates, which stresses that some chemoreceptor sites are of ancient origin.

Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus

Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a flipflop phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

Three-year follow-up of Interleukin 6 and C-reactive protein in chronic obstructive pulmonary disease

Background: Past studies have shown that mean values of Interleukin-6 (IL-6) and C-reactive protein (CRP) do not change significantly in COPD patients over a one-year period. However, longer period follow-up studies are still lacking. Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers. Methods: A cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV1, 56% predicted) were included in the prospective study. We evaluated Interleukin-6 (IL-6), C-reactive protein (CRP), six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years. Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry. Results: IL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; p < 0.001] and was associated with worse 6MWD performance. In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI) = 2.68 (0.13, 1.84); p = 0.02]. CRP mean values did not change [5 (1.6-7.9) vs 4.7 (1.7-10) pg/L; p = 0.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years. Conclusions: The systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients. Trial registration: No.:NCT00605540. © 2013 Ferrari et al; licensee BioMed Central Ltd.

Nucleotide and phylogenetic analysis of human papillomavirus types 6 and 11 isolated from recurrent respiratory papillomatosis in Brazil

There are few studies about the distribution of natural molecular variants of low-risk HPVs. Our aim was to evaluate the E6 early gene variability among HPV-6 and HPV-11 isolates detected in recurrent respiratory papillomatosis (RRP) samples obtained in a cohort of Brazilian patients. We also performed a phylogenetic analysis in order to compare nucleotide sequences identified in our study with previously reported isolates from different anatomic sites (laryngeal papillomas, genital warts, cervical cancer and anal swabs) obtained from other parts of the world to determine the phylogenetic relationships of variants detected in Brazil. The complete coding region of the E6 gene of 25 samples was cloned and sequenced: 18 isolates of HPV-6 (72%) and 7 isolates of HPV-11 (28%). A total of four different HPV-6 genomic variants and two HPV-11 genomic variants was identified. It was not possible to correlate specific variants with disease severity. Phylogenetic trees for both HPV types were constructed enclosing both E6 sequences detected in our study and formerly published sequences. In both phylogenetic trees, the sequences from Brazil did not group together. We could not establish a geographical association between HPV-6 or HPV-11 variants, unlike HPV-16 and HPV-18. © 2013 Elsevier B.V.

Effects of active smoking on airway and systemic inflammation profiles in patients with chronic obstructive pulmonary disease

Background: The markers that characterize local and systemic inflammation in chronic obstructive pulmonary disease (COPD) remain unclear, as do their correlations with smoking status and presence of disease. The aim of this study was to assess markers of inflammation in the peripheral blood and airways of current smokers without COPD, of current smokers with COPD and of ex-smokers with COPD. METHODS: In this study, 17 current smokers with COPD (mean age: 58.2 ± 9.6 years; mean forced expiratory volume in 1 second [FEV1]: 56.1 ± 15.9%), 35 ex-smokers with COPD (mean age: 66.3 ± 7.3 years; mean FEV1: 47.9 ± 17.2%) and 20 current smokers without COPD (mean age: 49.1 ± 6.2 years; mean FEV1: 106.5 ± 15.8%) were evaluated. Spirometry findings, body composition and serum/induced sputum concentrations of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8 and IL-10, together with serum C-reactive protein (CRP) levels, were assessed. RESULTS: Serum TNF-α concentration was higher in all current smokers than in ex-smokers with COPD. In current smokers without COPD, serum CRP level was lower than in ex-smokers with COPD and significantly lower than in current smokers with COPD. Sputum TNF-α concentration was higher in current and ex-smokers with COPD than in current smokers without COPD. Multiple regression analyses showed that serum TNF-α was associated with active smoking, and serum CRP and sputum TNF-α were associated with COPD diagnosis. CONCLUSIONS: Smoking is associated with higher systemic inflammation in patients with COPD. Current findings also support the hypothesis that smoking and COPD have different effects on the regulation of airway and systemic inflammatory processes. © 2013 Lippincott Williams and Wilkins.

Versão brasileira do Chronic Respiratory Questionnaire: estudo da validade de constructo e reprodutibilidade

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Perception and Attitude About Systemic Health and Periodontal Disease Among Dentistry Undergraduates

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Chronic obstructive pulmonary disease and heart rate variability: a literature update

Background: The literature indicates that chronic obstructive pulmonary disease (COPD) affects cardiac autonomic control. In this study, we conducted a literature review in order to investigate the heart rate variability (HRV) in COPD subjects. Methods: A search was performed in Medline database, using the link between the keywords: “autonomic nervous system”, “cardiovascular system”, “COPD” and “heart rate variability”. Results: The search resulted in a total of 40 references. Amongst these references, the first exclusion resulted in the barring of 29 titles and abstracts, which were not clearly related to the purpose of review. This resulted in a total of 11 articles that were then read and utilized in the review. The selected studies indicated that there is significant reduction of HRV in patients with COPD, characterized by reduction of indices that assess parasympathetic activity in addition to dealing with the global autonomic modulation. We also established that supervised exercise can reduce these harmful effects in COPD patients. Also, it was reported that the use of non-invasive ventilation in these patients may contribute to the improvement of respiratory symptoms, with no impairing, and may even induce positive responses in cardiac autonomic regulation. Conclusion: The studies indicate a need for further investigations to guide future therapies to improve the treatment of cardiovascular system in the respiratory diseases.

Respiratory manifestations of panic disorder in animals and humans: A unique opportunity to understand how supramedullary structures regulate breathing

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Animal models in chronic obstructive pulmonary disease-an overview

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airway obstruction resultant from an augmented inflammatory response of the respiratory tract to noxious particles and gases. Previous reports present a number of different hypotheses about the etiology and pathophysiology of COPD. The generating mechanisms of the disease are subject of much speculation, and a series of questions and controversies among experts still remain. In this context, several experimental models have been proposed in order to broaden the knowledge on the pathophysiological characteristics of the disease, as well as the search for new therapeutic approaches for acute or chronically injured lung tissue. This review aims to present the main experimental models of COPD, more specifically emphysema, as well as to describe the main characteristics, advantages, disadvantages, possibilities of application, and potential contribution of each of these models for the knowledge on the pathophysiological aspects and to test new treatment options for obstructive lung diseases.

Comparison between noninvasive mechanical ventilation and standard oxygen therapy in children up to 3 years old with respiratory failure after extubation: a pilot prospective randomized clinical study

Objectives: The effectiveness of noninvasive positive-pressure ventilation in preventing reintubation due to respiratory failure in children remains uncertain. A pilot study was designed to evaluate the frequency of extubation failure, develop a randomization approach, and analyze the feasibility of a powered randomized trial to compare noninvasive positive-pressure ventilation and standard oxygen therapy post extubation for preventing reintubation within 48 hours in children with respiratory failure.Design: Prospective pilot study.Setting: PICU at a university-affiliated hospital.Patients: Children aged between 28 days and 3 years undergoing invasive mechanical ventilation for greater than or equal to 48 hours with respiratory failure after programmed extubation.Interventions: Patients were prospectively enrolled and randomly assigned into noninvasive positive-pressure ventilation group and inhaled oxygen group after programmed extubation from May 2012 to May 2013.Measurements and Main Results: Length of stay in PICU and hospital, oxygenation index, blood gas before and after tracheal extubation, failure and reason for tracheal extubation, complications, mechanical ventilation variables before tracheal extubation, arterial blood gas, and respiratory and heart rates before and 1 hour after tracheal extubation were analyzed. One hundred eight patients were included (noninvasive positive-pressure ventilation group, n = 55 and inhaled oxygen group, n = 53), with 66 exclusions. Groups did not significantly differ for gender, age, disease severity, Pediatric Risk of Mortality at admission, tracheal intubation, and mechanical ventilation indications. There was no statistically significant difference in reintubation rate (noninvasive positive-pressure ventilation group, 9.1%; inhaled oxygen group, 11.3%; p > 0.05) and length of stay (days) in PICU (noninvasive positive-pressure ventilation group, 3 [116]; inhaled oxygen group, 2 [1-25]; p > 0.05) or hospital (noninvasive positive-pressure ventilation group, 19 [7-141]; inhaled oxygen group, 17 [8-80]).Conclusions: The study indicates that a larger randomized trial comparing noninvasive positive-pressure ventilation and standard oxygen therapy in children with respiratory failure is feasible, providing a basis for a future trial in this setting. No differences were seen between groups. The number of excluded patients was high.

Physiological and pathophysiological interactions between the respiratory central pattern generator and the sympathetic nervous system

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Disease resistance of pacu Piaractus mesopotamicus (Holmberg, 1887) fed with beta-glucan

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)