Microbiological insights into respiratory infections and the opportunities for inhaled therapy

Respiratory infections represent the fourth most common cause of all deaths across age groups and countries. Treating these infections appropriately is a clear clinical priority and here we outline the types of therapy that are in current use for some of these infections. It is important that treatments are further improved and the potential of inhaled delivery to fulfil this need is considered. We describe novel methodologies that are being applied for the identification and enumeration of microorganisms in the respiratory tract, and propose that ways of improving therapy may arise from understanding better the etiology of respiratory infection and the impact of inhaled drug therapies. The potential for translational benefits for patients are also discussed.

One-step reverse transcriptase polymerase chain reaction for the diagnosis of respiratory syncytial virus in children

Human respiratory syncytial virus (HRSV) is the main cause of acute lower respiratory tract infections in infants and children. Rapid diagnosis is required to permit appropriate care and treatment and to avoid unnecessary antibiotic use. Reverse transcriptase (RT-PCR) and indirect immunofluorescence assay (IFA) methods have been considered important tools for virus detection due to their high sensitivity and specificity. In order to maximize use-simplicity and minimize the risk of sample cross-contamination inherent in two-step techniques, a RT-PCR method using only a single tube to detect HRSV in clinical samples was developed. Nasopharyngeal aspirates from 226 patients with acute respiratory illness, ranging from infants to 5 years old, were collected at the University Hospital of the University of Sao Paulo (HU-USP), and tested using IFA, one-step RT-PCR, and semi-nested RT-PCR. One hundred and two (45.1%) samples were positive by at least one of the three methods, and 75 (33.2%) were positive by all methods: 92 (40.7%) were positive by one-step RT-PCR, 84 (37.2%) by IFA, and 96 (42.5%) by the semi-nested RT-PCR technique. One-step RT-PCR was shown to be fast, sensitive, and specific for RSV diagnosis, without the added inconvenience and risk of false positive results associated with semi-nested PCR. The combined use of these two methods enhances HRSV detection. (C) 2007 Elsevier B.V. All rights reserved.

Pulmonary Surfactant in Respiratory Syncytial Virus Bronchiolitis: The Role in Pathogenesis and Clinical Implications

Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of lower respiratory tract infection, and the most frequent reason for hospitalization among infants throughout the world. In addition to the acute consequences of the disease, RSV bronchiolitis in early childhood is related to further development of recurrent wheezing and asthma. Despite the medical and economic burden of the disease, therapeutic options are limited to supportive measures, and mechanical ventilation in severe cases. Growing evidence suggests an important role of changes in pulmonary surfactant content and composition in the pathogenesis of severe RSV bronchiolitis. Besides the well-known importance of pulmonary surfactant in maintenance of pulmonary homeostasis and lung mechanics, the surfactant proteins SP-A and SP-D are essential components of the pulmonary innate immune system. Deficiencies of such proteins, which develop in severe RSV bronchiolitis, may be related to impairment in viral clearance, and exacerbated inflammatory response. A comprehensive understanding of the role of the pulmonary surfactant in the pathogenesis of the disease may help the development of new treatment strategies. We conducted a review of the literature to analyze the evidences of pulmonary surfactant changes in the pathogenesis of severe RSV bronchiolitis, its relation to the inflammatory and immune response, and the possible role of pulmonary surfactant replacement in the treatment of the disease. Pediatr Pulmonol. 2011; 46:415-420. (c) 2010 Wiley-Liss, Inc.

Association between particulate matter from biomass burning and respiratory diseases in the southern region of the Brazilian Amazon

Objective. To investigate the short-term effects of exposure to particulate matter from biomass burning in the Amazon on the daily demand for outpatient care due to respiratory diseases in children and the elderly. Methods. Epidemiologic study with ecologic time series design. Daily consultation records were obtained from the 14 primary health care clinics in the municipality of Alta Floresta, state of Mato Grosso, in the southern region of the Brazilian Amazon, between January 2004 and December 2005. Information on the daily levels of fine particulate matter was made available by the Brazilian National Institute for Spatial Research. To control for confounding factors ( situations in which a non-causal association between exposure and disease is observed due to a third variable), variables related to time trends, seasonality, temperature, relative humidity, rainfall, and calendar effects ( such as occurrence of holidays and weekends) were included in the model. Poisson regression with generalized additive models was used. Results. A 10 mu g/m(3) increase in the level of exposure to particulate matter was associated with increases of 2.9% and 2.6% in outpatient consultations due to respiratory diseases in children on the 6th and 7th days following exposure. Significant associations were not observed for elderly individuals. Conclusions. The results suggest that the levels of particulate matter from biomass burning in the Amazon are associated with adverse effects on the respiratory health of children.

The cost of community-managed viral respiratory illnesses in a cohort of healthy preschool-aged children

Background : Acute respiratory illnesses (ARIs) during childhood are often caused by respiratory viruses, result in significant morbidity, and have associated costs for families and society. Despite their ubiquity, there is a lack of interdisciplinary epidemiologic and economic research that has collected primary impact data, particularly associated with indirect costs, from families during ARIs in children.
Methods : We conducted a 12-month cohort study in 234 preschool children with impact diary recording and PCR testing of nose-throat swabs for viruses during an ARI. We used applied values to estimate a virus-specific mean cost of ARIs.
Results : Impact diaries were available for 72% (523/725) of community-managed illnesses between January 2003 and January 2004. The mean cost of ARIs was AU$309 (95% confidence interval $263 to $354). Influenza illnesses had a mean cost of $904, compared with RSV, $304, the next most expensive single-virus illness, although confidence intervals overlapped. Mean carer time away from usual activity per day was two hours for influenza ARIs and between 30 and 45 minutes for all other ARI categories.
Conclusion : From a societal perspective, community-managed ARIs are a significant cost burden on families and society. The point estimate of the mean cost of community-managed influenza illnesses in healthy preschool aged children is three times greater than those illnesses caused by RSV and other respiratory viruses. Indirect costs, particularly carer time away from usual activity, are the key cost drivers for ARIs in children. The use of parent-collected specimens may enhance ARI surveillance and reduce any potential Hawthorne effect caused by compliance with study procedures. These findings reinforce the need for further integrated epidemiologic and economic research of ARIs in children to allow for comprehensive cost-effectiveness assessments of preventive and therapeutic options.

Microfluidic platforms for biomarker analysis

Biomarkers have been described as characteristics, most often molecular, that provide information about biological states, whether normal, pathological, or therapeutically modified. They hold great potential to assist diagnosis and prognosis, monitor disease, and assess therapeutic effectiveness. While a few biomarkers are routinely utilised clinically, these only reflect a very small percentage of all biomarkers discovered. Numerous factors contribute to the slow uptake of these new biomarkers, with challenges faced throughout the biomarker development pipeline. Microfluidics offers two important opportunities to the field of biomarkers: firstly, it can address some of these developmental obstacles, and secondly, it can provide the precise and complex platform required to bridge the gap between biomarker research and the biomarker-based analytical device market. Indeed, adoption of microfluidics has provided a new avenue for advancement, promoting clinical utilisation of both biomarkers and their analytical platforms. This review will discuss biomarkers and outline microfluidic platforms developed for biomarker analysis.

Métodos para abandono do tabagismo e tratamento da dependência da nicotina

O tabagismo está relacionado a 30% das mortes por câncer. É fator de risco para desenvolver carcinomas do aparelho respiratório, esôfago, estômago, pâncreas, cérvix uterina, rim e bexiga. A nicotina induz tolerância e dependência pela ação nas vias dopaminérgicas centrais, levando às sensações de prazer e recompensa mediadas pelo sistema límbico. É estimulante do sistema nervoso central (SNC), aumenta o estado de alerta e reduz o apetite. A diminuição de 50% no consumo da nicotina pode desencadear sintomas de abstinência nos indivíduos dependentes: ansiedade, irritabilidade, distúrbios do sono, aumento do apetite, alterações cognitivas e fissura pelo cigarro. O aconselhamento médico é fundamental para o sucesso no abandono do fumo. A farmacoterapia da dependência de nicotina divide-se em: primeira linha (bupropiona e terapia de reposição da nicotina), e segunda linha (clonidina e nortriptilina). A bupropiona é um antidepressivo não-tricíclico que age inibindo a recaptação de dopamina, cujas contra-indicações são: epilepsia, distúrbios alimentares, hipertensão arterial não-controlada, abstinência recente do álcool e uso de inibidores da monoaminoxidase (MAO). A terapia de reposição de nicotina pode ser feita com adesivos e gomas de mascar. Os efeitos da acupuntura no abandono do fumo ainda não estão completamente esclarecidos. As estratégias de interrupção abrupta ou redução gradual do fumo têm a mesma probabilidade de sucesso.

Viral etiology among the elderly presenting acute respiratory infection during the influenza season

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

Seasonality of viral respiratory infections in Southeast of Brazil: the influence of temperature and air humidity

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

Diversity and Adaptation of Human Respiratory Syncytial Virus Genotypes Circulating in Two Distinct Communities: Public Hospital and Day Care Center

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

Human respiratory syncytial virus detection in children admitted at a community hospital in Botucatu, SP, Brazil

O Vírus Respiratório Sincicial Humano (VRSH) é descrito como o mais importante patógeno viral causador de doenças respiratórias agudas das vias respiratórias inferiores em crianças. Neste estudo 84 amostras de crianças com idade abaixo dos dois anos apresentando sintomas de doença respiratória aguda, foram obtidas no período de setembro de 2000 a novembro de 2001. Analise por imunofluorescência indireta e transcrição reversa seguida de PCR, revelou que 18% (15/84) das amostras foram positivas, sendo que em 80% (12/15) dos casos a detecção de VRSH foi observada em crianças abaixo dos seis meses, e também que os subgrupos A e B co-circularam. Estes são os primeiros dados obtidos para a cidade de Botucatu, sendo que a sazonalidade mostrou-se evidente pela maior circulação desse vírus entre os meses de maio e julho

Respiratory heat loss of Holstein cows in a tropical environment

In order to develop statistical models to predict respiratory heat loss in dairy cattle using simple physiological and environmental measurements, 15 Holstein cows were observed under field conditions in a tropical environment, in which the air temperature reached up to 40 ° C. The measurements of latent and sensible heat loss from the respiratory tract of the animals were made by using a respiratory mask. The results showed that under air temperatures between 10 and 35 ° C sensible heat loss by convection decreased from 8.24 to 1.09 W m(-2), while the latent heat loss by evaporation increased from 1.03 to 56.51 W m(-2). The evaporation increased together with the air temperature in almost a linear fashion until 20 ° C, but it became increasingly high as the air temperature rose above 25 ° C. Convection was a mechanism of minor importance for respiratory heat transfer. In contrast, respiratory evaporation was an effective means of thermoregulation for Holsteins in a hot environment. Mathematical models were developed to predict both the sensible and latent heat loss from the respiratory tract in Holstein cows under field conditions, based on measurements of the ambient temperature, and other models were developed to predict respiration rate, tidal volume, mass flow rate and expired air temperature as functions of the ambient temperature and other variables.

Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients

The risk for venous thromboembolism (VTE) in medical patients is high, but risk assessment is rarely performed because there is not yet a good method to identify candidates for prophylaxis. Purpose: To perform a systematic review about VTE risk factors (RFs) in hospitalized medical patients and generate recommendations (RECs) for prophylaxis that can be implemented into practice. Data sources: A multidisciplinary group of experts from 12 Brazilian Medical Societies searched MEDLINE, Cochrane, and LILACS. Study selection: Two experts independently classified the evidence for each RF by its scientific quality in a standardized manner. A risk-assessment algorithm was created based on the results of the review. Data synthesis: Several VTE RFs have enough evidence to support RECs for prophylaxis in hospitalized medical patients (eg, increasing age, heart failure, and stroke). Other factors are considered adjuncts of risk (eg, varices, obesity, and infections). According to the algorithm, hospitalized medical patients ≥40 years-old with decreased mobility, and ≥1 RFs should receive chemoprophylaxis with heparin, provided they don't have contraindications. High prophylactic doses of unfractionated heparin or low-molecular-weight-heparin must be administered and maintained for 6-14 days. Conclusions: A multidisciplinary group generated evidence-based RECs and an easy-to-use algorithm to facilitate VTE prophylaxis in medical patients. © 2007 Rocha et al, publisher and licensee Dove Medical Press Ltd.

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.

Análise do gene E6 de HPV de baixo risco em papilomatose de laringe

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