926 resultados para pulmonary function decline


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A interleucina 13 (IL-13) tem sido apontada como um dos principais mediadores em processos de ativação de fibroblastos e indução de fibrose pulmonar, sendo, portanto, considerada como um alvo terapêutico importante. A silicose é uma doença pulmonar inflamatória crônica, de caráter ocupacional, caracterizada por uma intensa resposta fibrótica e granulomatosa. Com base nestas observações, tivemos por objetivo investigar o potencial efeito da administração da imunotoxina IL-13-PE38QQR (IL-13PE) sobre o modelo de silicose em camundongos. Camundongos Swiss-Webster foram anestesiados e instilados intranasalmente com partículas de sílica (10 mg), sendo a administração da IL-13PE (200ng/dia) realizada por via intranasal, uma vez ao dia em dias alternados no período entre 21 a 27 dias após a provocação. Analisamos o componente inflamatório, a deposição de colágeno e a área de granuloma avaliados através de técnicas clássicas de histologia, incluindo coloração com H&E e Picrus-sirius, ou ainda a quantificação do conteúdo de colágeno por Sircol. Os componentes de matriz extracelular fibronectina e laminina foram avaliados através de imunohistoquímica. Citocinas e quimiocinas foram quantificadas por sistema de ELISA. As medidas de função pulmonar e resposta de hiperreatividade foram realizadas através do sistema de pletismografia de corpo inteiro invasiva. Verificamos que o tratamento curativo com a IL-13PE inibiu de forma acentuada o comprometimento da função pulmonar nos camundongos silicóticos, incluindo tanto aumento da resistência como da elastância, assim como a resposta de hiperratividade das vias aéreas ao agente broncoconstrictor metacolina. De forma coerente, os animais silicóticos quando submetidos ao tratamento com IL-13PE apresentaram marcada redução do componente inflamatório pulmonar e da resposta fibrótica, atestado pela diminuição na produção de colágeno, laminina e fibronectina e redução importante da área de granuloma. De forma semelhante, as citocinas (TNF-α e TGF-) e quimiocinas (MIP-1α, MIP-2, TARC, IP-10, MDC) detectadas em quantidade aumentada no pulmão de animais silicóticos foram reduzidas pelo tratamento com a IL-13PE. Em conclusão, nossos resultados mostram que a administração curativa da IL-13PE foi capaz de inibir os componentes inflamatórios e fibróticos da fase crônica do quadro silicótico em camundongos, o que se refletiu de forma clara na melhora da função pulmonar. Em conjunto, nossos achados indicam que a utilização da IL13PE parece constituir uma abordagem terapêutica extremamente promissora para aplicação em casos de doenças crônicas de natureza fibrótica como a silicose.

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Background With the increasing of an elderly population, the number of both vascular disease and cognitive function is increasing. Recent study shown that there is close relationship between vascular disease or vascular risk factors and cognitive function, but many questions are unclear. Objective The aim of this study was to explore the status of cognitive function of midlife and elderly subjects and to evaluate association between vascular risk factors and cognitive function. Methods We selected 330(female,128,male,202) retire navy veterans aged between 55 and 87 years old in Beijing. The average age was 67 years old. Data about vascular risk factors, including: history of cerebral infarction, cardiovascular disease, hypertension, diabetes mellitus, carotid lesions, cigarette smoking, drinking, obesity, and so on. Cognitive functions were assessed by neuropsychological tests: the four tasks of working memory. Results The univariate analysis indicated that there were significant differences of working memory scores in aging, gender, education level, the history of stroke, hypertension with midlife and elderly subjects. Moderate levels of alcohol intake maybe better for cognition. Conclusion vascular disease and some vascular risk factors may lead to cognitive function decline, thus, intervention methods should be carried out in middle and elderly people with vascular risk fact should be under special supervision, with at least annual neuropsychological evaluation. Key words: cognitive function; vascular risk factor, working memory.

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BACKGROUND: Previous investigation showed that the volume-time curve technique could be an alternative for endotracheal tube (ETT) cuff management. However, the clinical impact of the volume-time curve application has not been documented. the purpose of this study was to compare the occurrence and intensity of a sore throat, cough, thoracic pain, and pulmonary function between these 2 techniques for ETT cuff management: volume-time curve technique versus minimal occlusive volume (MOV) technique after coronary artery bypass grafting. METHODS: A total of 450 subjects were randomized into 2 groups for cuff management after intubation: MOV group (n = 222) and volume-time curve group (n = 228). We measured cuff pressure before extubation. We performed spirometry 24 h before and after surgery. We graded sore throat and cough according to a 4-point scale at 1, 24, 72, and 120 h after extubation and assessed thoracic pain at 24 h after extubation and quantified the level of pain by a 10-point scale. RESULTS: the volume-time curve group presented significantly lower cuff pressure (30.9 +/- 2.8 vs 37.7 +/- 3.4 cm H2O), less incidence and intensity of sore throat (1 h, 23.7 vs 51.4%; and 24 h, 18.9 vs 40.5%, P < .001), cough (1 h, 19.3 vs 48.6%; and 24 h, 18.4 vs 42.3%, P < .001), thoracic pain (5.2 +/- 1.8 vs 7.1 +/- 1.7), better preservation of FVC (49.5 +/- 9.9 vs 41.8 +/- 12.9%, P = .005), and FEV1, (46.6 +/- 1.8 vs 38.6 +/- 1.4%, P = .005) compared with the MOV group. CONCLUSIONS: the subjects who received the volume-time curve technique for ETT cuff management presented a significantly lower incidence and severity of sore throat and cough, less thoracic pain, and minimally impaired pulmonary function than those subjects who received the MOV technique during the first 24 h after coronary artery bypass grafting.

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Background: Self-management education may help patients with cystic fibrosis and their families to choose, monitor and adjust treatment requirements for their illness, and also to manage the effects of illness on their lives. Although self-management education interventions have been developed for cystic fibrosis, no previous systematic review of the evidence of effectiveness of these interventions has been conducted. Objectives: To assess the effects of self-management education interventions on improving health outcomes for patients with cystic fibrosis and their caregivers. Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register (date of the last search: 22 August 2013). We also searched databases through EBSCO (CINAHL; Psychological and Behavioural Sciences Collection; PsychInfo; SocINDEX) and Elsevier (Embase) and handsearched relevant journals and conference proceedings (date of the last searches: 01 February 2014 ). Selection criteria: Randomised controlled trials, quasi-randomised controlled trials or controlled clinical trials comparing different types of self-management education for cystic fibrosis or comparing self-management education with standard care or no intervention. Data collection and analysis: Two authors assessed trial eligibility and risk of bias. Three authors extracted data. Main results: Four trials (involving a total of 269 participants) were included. The participants were children with cystic fibrosis and their parents or caregivers in three trials and adults with cystic fibrosis in one trial. The trials compared four different self-management education interventions versus standard treatment: (1) a training programme for managing cystic fibrosis in general; (2) education specific to aerosol and airway clearance treatments; (3) disease-specific nutrition education; and (4) general and disease-specific nutrition education. Training children to manage cystic fibrosis in general had no statistically significant effects on weight after six to eight weeks, mean difference -7.74 lb (i.e. 3.51 kg) (95% confidence interval -35.18 to 19.70). General and disease-specific nutrition education for adults had no statistically significant effects on: pulmonary function (forced expiratory volume at one second), mean difference -5.00 % (95% confidence interval -18.10 to 8.10) at six months and mean difference -5.50 % (95% confidence interval -18.46 to 7.46) at 12 months; or weight, mean difference - 0.70 kg (95% confidence interval -6.58 to 5.18) at six months and mean difference -0.70 kg (95% confidence interval -6.62 to 5.22) at 12 months; or dietary fat intake scores, mean difference 1.60 (85% confidence interval -2.90 to 6.10) at six months and mean difference 0.20 (95% confidence interval -4.08 to 4.48) at 12 months. There is some limited evidence to suggest that self-management education may improve knowledge in patients with cystic fibrosis but not in parents or caregivers. There is also some limited evidence to suggest that self-management education may result in positively changing a small number of behaviours in both patients and caregivers. Authors' conclusions: The available evidence from this review is of insufficient quantity and quality to draw any firm conclusions about the effects of self-management education for cystic fibrosis. Further trials are needed to investigate the effects of self-management education on a range of clinical and behavioural outcomes in children, adolescents and adults with cystic fibrosis and their caregivers.

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BACKGROUND: The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO2peak), patient-reported outcomes, and the organ components that govern VO2peak in post-operative non-small cell lung cancer (NSCLC) patients. METHODS/DESIGN: Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO2peak for aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO2peak. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression. DISCUSSION: VO2peak is becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum. TRIAL REGISTRATION: NCT00018255.

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BACKGROUND: One of the central physiological functions of the lungs is to transfer inhaled gases from the alveoli to pulmonary capillary blood. However, current measures of alveolar gas uptake provide only global information and thus lack the sensitivity and specificity needed to account for regional variations in gas exchange. METHODS AND PRINCIPAL FINDINGS: Here we exploit the solubility, high magnetic resonance (MR) signal intensity, and large chemical shift of hyperpolarized (HP) (129)Xe to probe the regional uptake of alveolar gases by directly imaging HP (129)Xe dissolved in the gas exchange tissues and pulmonary capillary blood of human subjects. The resulting single breath-hold, three-dimensional MR images are optimized using millisecond repetition times and high flip angle radio-frequency pulses, because the dissolved HP (129)Xe magnetization is rapidly replenished by diffusive exchange with alveolar (129)Xe. The dissolved HP (129)Xe MR images display significant, directional heterogeneity, with increased signal intensity observed from the gravity-dependent portions of the lungs. CONCLUSIONS: The features observed in dissolved-phase (129)Xe MR images are consistent with gravity-dependent lung deformation, which produces increased ventilation, reduced alveolar size (i.e., higher surface-to-volume ratios), higher tissue densities, and increased perfusion in the dependent portions of the lungs. Thus, these results suggest that dissolved HP (129)Xe imaging reports on pulmonary function at a fundamental level.

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BACKGROUND:
A previous retrospective study suggested that a policy of regular anti-pseudomonal antibiotic treatment improved pulmonary function and increased survival in patients with cystic fibrosis chronically infected with Pseudomonas species. The results of a prospective multicentre study to compare the effects on pulmonary function and mortality of three monthly elective anti-pseudomonal antibiotic treatment with conventional symptomatic treatment are reported.

METHODS:
Sixty patients with cystic fibrosis, chronically infected with P aeruginosa, were randomised to the two treatment arms (elective or symptomatic) and followed clinically at yearly reviews. The major end points were changes in forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). Survival was a secondary end point.

RESULTS:
Patients in the symptomatic group received a mean of three antibiotic treatments each year and those in the elective group received four antibiotic treatments during each year of the study. No significant differences in FEV(1) and FVC were found between the two groups after three years. There was a statistically non-significant higher rate of deaths in the elective group (n = 4), three of which were associated with B cepacia infection, compared with the symptomatic group (n = 0).

CONCLUSIONS:
This study did not demonstrate an advantage of a policy of elective antibiotic treatment over symptomatic treatment in patients with cystic fibrosis chronically infected with Pseudomonas species.

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Background: It has been suggested that asthmatic subjects with persisting symptoms despite adequate maintenance therapy should be systematically evaluated to identify factors contributing to poor control. The aims of this study were to examine the prevalence of these factors in a cohort of sequentially referred poorly controlled asthmatics, and to determine if any factor or combination of factors predicted true therapy resistant asthma (TRA).

Methods: Patients were evaluated using a systematic evaluation protocol including induced sputum analysis, psychiatric assessment, ear, nose and throat examination, pulmonary function testing, high resolution CT scan of the thorax, and 24 hour dual probe ambulatory oesophageal pH monitoring; any identified provoking factor was treated. Asthma was managed according to BTS guidelines.

Results: Of 73 subjects who completed the assessment, 39 responded to intervention and 34 had TRA. Subjects with TRA had a greater period of instability, a higher dose of inhaled steroids at referral, more rescue steroid use, and a lower best percentage forced expiratory volume in 1 second (FEV1%). Oesophageal reflux, upper airway disease, and psychiatric morbidity were common (57%, 95%, 49%, respectively) but were not more prevalent in either group. Using multivariate logistic regression analysis, inhaled steroid dose >2000 µg BDP, previous assessment by a respiratory specialist, and initial FEV1% of <70% at referral predicted a final diagnosis of TRA.

Conclusions: In poorly controlled asthmatics there is a high prevalence of co-morbidity, identified by detailed systematic assessment, but no difference in prevalence between those who respond to intervention and those with TRA. Targeted treatment of identified co-morbidities has minimal impact on asthma related quality of life in those with therapy resistant disease.

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Background: The purpose of this systematic literature review was to examine current empirical research on general and respiratory health outcomes in adult survivors of bronchopulmonary dysplasia (BPD).

Methods: We searched seven databases up to the end of November 2010 (MEDLINE, PubMed, EMBASE, PsycINFO, Maternity and Infant Care, Cumulative Index of Nursing and Allied Health Literature, and Web of Knowledge). We independently screened and included only those studies concerning the assessment of outcome measures in adult survivors of BPD. Data on methodologic design and findings were extracted from each included study; in addition, the methodologic quality of each study was assessed using the Critical Appraisal Skills Programme checklist.

Results: Fourteen cohort studies met the review criteria. Of those, a total of eight studies were considered to be of high quality (score 9-12), five of moderate quality (score 5-8), and only one was of low quality (score 0-4). In all studies of adult survivors of BPD, differences were found between the index and control groups, suggesting that many adults survivors of BPD who were born preterm or with very low birth weight had more respiratory symptoms and pulmonary function abnormalities compared with their peers. Five studies concerning radiologic findings reported structural changes persisting into adulthood. Findings from three studies suggested impairment in exercise capacity, although firm conclusions were limited by the small sample size in the studies reviewed.

Conclusions: Compared with adults born at term, adult survivors of BPD have more impairment in general and respiratory health, which does not seem to diminish over time.

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Background:

Increasing the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential treatment for cystic fibrosis.

Methods:

We conducted a randomized, double-blind, placebo-controlled trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of age or older with cystic fibrosis and at least one G551D-CFTR mutation. Subjects were randomly assigned to receive 150 mg of ivacaftor every 12 hours (84 subjects, of whom 83 received at least one dose) or placebo (83, of whom 78 received at least one dose) for 48 weeks. The primary end point was the estimated mean change from baseline through week 24 in the percent of predicted forced expiratory volume in 1 second (FEV1).

Results:

The change from baseline through week 24 in the percent of predicted FEV1 was greater by 10.6 percentage points in the ivacaftor group than in the placebo group (P < 0.001). Effects on pulmonary function were noted by 2 weeks, and a significant treatment effect was maintained through week 48. Subjects receiving ivacaftor were 55% less likely to have a pulmonary exacerbation than were patients receiving placebo, through week 48 (P < 0.001). In addition, through week 48, subjects in the ivacaftor group scored 8.6 points higher than did subjects in the placebo group on the respiratory-symptoms domain of the Cystic Fibrosis Questionnaire-revised instrument (a 100-point scale, with higher numbers indicating a lower effect of symptoms on the patient's quality of life) (P < 0.001). By 48 weeks, patients treated with ivacaftor had gained, on average, 2.7 kg more weight than had patients receiving placebo (P < 0.001). The change from baseline through week 48 in the concentration of sweat chloride, a measure of CFTR activity, with ivacaftor as compared with placebo was -48.1 mmol per liter (P < 0.001). The incidence of adverse events was similar with ivacaftor and placebo, with a lower proportion of serious adverse events with ivacaftor than with placebo (24% vs. 42%).

Conclusions:

Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through 48 weeks. Substantial improvements were also observed in the risk of pulmonary exacerbations, patient-reported respiratory symptoms, weight, and concentration of sweat chloride.

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BACKGROUND: Obesity has emerged as a risk factor for the development of asthma and it may also influence asthma control and airways inflammation. However, the role of obesity in severe asthma remains unclear. OBJECTIVE: To explore the association between obesity (defined by BMI) and severe asthma. METHODS: Data from the National Registry for dedicated UK Difficult Asthma Services were used to compare patient demographics, disease characteristics and healthcare utilisation between three body mass index (BMI) categories (normal weight: 18.5 -24.99, overweight: 25 -29.99, obese: =30) in a well characterised group of severe asthmatic adults. RESULTS: The study population consisted of 666 severe asthmatics with a median BMI of 29.8 (interquartile range 22.5 -34.0). The obese group exhibited greater asthma medication requirements in terms of maintenance corticosteroid therapy (48.9% versus 40.4% and 34.5% in the overweight and normal weight groups, respectively), steroid burst therapy and short-acting ß2-agonist (SABA) use per day. Significant differences were seen with gastro-oesophageal reflux disease (GORD) (53.9% versus 48.1% and 39.7% in the overweight and normal weight groups, respectively) and proton pump inhibitor (PPI) use. Bone density scores were higher in the obese group, whilst pulmonary function testing revealed a reduced FVC and raised Kco. Serum IgE levels decreased with increasing BMI and the obese group were more likely to report eczema, but less likely to have a history of nasal polyps. CONCLUSIONS: Severe asthmatics display particular characteristics according to BMI that support the view that obesity associated severe asthma may represent a distinct clinical phenotype.1Royal Brompton Hospital, London, UK;2Department of Computing, Imperial College, UK3Airways Disease, National Heart & Lung Institute, Imperial College, UK;4Centre for infection and immunity, Queen's University of Belfast, UK;5University of Leicester, UK;6The University of Manchester and University Hospital of South Manchester, UK;7Birmingham Heartlands Hospital, University of Birmingham, UK;8Gartnavel General Hospital, University of Glasgow, UK;9Glasgow Royal Infirmary, Glasgow, UKCorrespondence: Dr Andrew N. Menzies-Gow, Royal Brompton Hospital, Fulham Road, London SW3 6HP.

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Although survival has improved significantly in recent years, prematurity remains a major cause of infant and childhood mortality and morbidity. Preterm births (<37 weeks of gestation) account for 8% of live births representing >50 000 live births each year in the UK. Preterm birth, irrespective of whether babies require neonatal intensive care, is associated with increased respiratory symptoms, partially reversible airflow obstruction and abnormal thoracic imaging in childhood and in young adulthood compared with those born at term. Having failed to reach their optimal peak lung function in early adulthood, there are as yet unsubstantiated concerns of accelerated lung function decline especially if exposed to noxious substances leading to chronic respiratory illness; even if the rate of decline in lung function is normal, the threshold for respiratory symptoms will be crossed early. Few adult respiratory physicians enquire about the neonatal period in their clinical practice. The management of these subjects in adulthood is largely evidence free. They are often labelled as asthmatic although the underlying mechanisms are likely to be very different. Smoking cessation, maintaining physical fitness, annual influenza immunisation and a general healthy lifestyle should be endorsed irrespective of any symptoms. There are a number of clinical and research priorities to maximise the quality of life and lung health in the longer term not least understanding the underlying mechanisms and optimising treatment, rather than extrapolating from other airway diseases.

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BACKGROUND: Exhaled breath temperature (EBT) reflects airways (both eosinophilic and neutrophilic) inflammation in asthma and thus may aid the management of children with asthma that are treated with anti-inflammatory drugs. A new EBT monitor has become available that is cheap and easy to use and may be a suitable monitoring device for airways inflammation. Little is known about how EBT relates to asthma treatment decisions, disease control, lung function, or other non-invasive measures of airways inflammation, such as exhaled nitric oxide (ENO).

OBJECTIVE: To determine the relationships between EBT and asthma treatment decision, current control, pulmonary function, and ENO.

METHODS: Cross-sectional prospective study on 159 children aged 5-16 years attending a pediatric respiratory clinic. EBT was compared with the clinician's decision regarding treatment (decrease, no change, increase), asthma control assessment (controlled, partial, uncontrolled), level of current treatment (according to British Thoracic Society guideline, BTS step), ENO, and spirometry.

RESULTS: EBT measurement was feasible in the majority of children (25 of 159 could not perform the test) and correlated weakly with age (R = 0.33, P = <0.01). EBT did not differ significantly between the three clinician decision groups (P = 0.42), the three asthma control assessment groups (P = 0.9), or the current asthma treatment BTS step (P = 0.57).

CONCLUSIONS & CLINICAL IMPLICATIONS: EBT measurement was not related to measures of asthma control determined at the clinic. The routine intermittent monitoring of EBT in children prescribed inhaled corticosteroids who attend asthma clinics cannot be recommended for adjusting anti-inflammatory asthma therapy.

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A substantial proportion of aetiological risks for many cancers and chronic diseases remain unexplained. Using geochemical soil and stream water samples collected as part of the Tellus Project studies, current research is investigating naturally occurring background levels of potentially toxic elements (PTEs) in soils and stream sediments and their possible relationship with progressive chronic kidney disease (CKD). The Tellus geological mapping project, Geological Survey Northern Ireland, collected soil sediment and stream water samples on a grid of one sample site every 2 km2 across the rural areas of Northern Ireland resulting in an excess of 6800 soil sampling locations and more than 5800 locations for stream water sampling. Accumulation of several PTEs including arsenic, cadmium, chromium, lead and mercury have been linked with human health and implicated in renal function decline. The hypothesis is that long-term exposure will result in cumulative exposure to PTEs and act as risk factor(s) for cancer and diabetes related CKD and its progression. The ‘bioavailable’ fraction of total PTE soil concentration depends on the ‘bioaccessible’ proportion through an exposure pathway. Recent work has explored this bioaccessible fraction for a range of PTEs across Northern Ireland. In this study the compositional nature of the multivariate geochemical PTE variables and bioaccessible data is explored to augment the investigation into the potential relationship between PTEs, bioaccessibility and disease data.

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Agricultural workers especially poultry farmers are at increased risk of occupational respiratory diseases. Epidemiological studies showed increased prevalence of respiratory symptoms and adverse changes in pulmonary function parameters in poultry workers. In poultry production volatile organic compounds (VOCs) presence can be due to some compounds produced by molds that are volatile and are released directly into the air. These are known as microbial volatile organic compounds (MVOCs). Because these compounds often have strong and/or unpleasant odors, they can be the source of odors associated with molds. MVOC's are products of the microorganisms primary and secondary metabolism and are composed of low molecular weight alcohols, aldehydes, amines, ketones, terpenes, aromatic and chlorinated hydrocarbons, and sulfur-based compounds, all of which are variations of carbon-based molecules.