Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation which flare-up during episodes of acute exacerbation (AECOPD). Given the role of Toll-like receptors (TLRs) in the induction of inflammatory responses we investigated the involvement of TLRs in COPD pathogenesis.

Active carers: living with chronic obstructive pulmonary disease

It has long been recognised that the majority of care provided in chronic illness comes not from health and social care professionals, but from family and friends. One such illness is chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality in the developed world.To explore the specific care needs of informal caregivers of patients with advanced COPD, interviews were conducted with seven active family caregivers. Interviews were taped, transcribed and content analysed to obtain the caregivers' needs. Results confirm that family caregivers provide direct care with little support and assistance. Participants reported restricted activities of daily living and some emotional distress. There were knowledge deficiencies among caregivers relating to the COPD illness trajectory and little awareness of the potential of palliative care. Family caregivers need social and professional support while caring for a patient at home. This would help to ensure that their physical and emotional health does not suffer. There is a need to devise interventions to ensure family caregivers are supported.

Experiences and needs of bereaved carers during palliative and end-of-life care for people with chronic obstructive pulmonary disease

This study explored the experiences of palliative care that bereaved carers had while providing care to a dying loved one with chronic obstructive pulmonary disease (COPD).

Method: Semi-structured interviews were undertaken with nine carers whohad lost a loved one in the preceding 6 to 24 months.These interviews explored levels of satisfaction with disease management, symptom management, and end-of-life care. With permission, interviews were tape recorded, transcribed, and subjected to content analysis.

Findings: Three themes emerged from the data: the impact of the caring experience, the lack of support services, and end-of-life and bereavement support. Carers experienced carer burden, lack of access to support services, a need for palliative care, and bereavement support.

Conclusion: The findings provide a first insight into the experiences of carers of patients with advanced COPD. Bereaved carers of patients who had suffered advanced COPD reported that they had received inadequate support and had a range of unmet palliative care needs. Special attention should be paid to educating and supporting carers during their caring and bereavement periods to ensure that their quality of life is maintained or enhanced

Protocolized versus non-protocolized weaning for reducing the duration of mechanical ventilation in critically ill adult patients (Review)

BACKGROUND: Reducing weaning time is desirable in minimizing potential complications from mechanical ventilation. Standardized weaning protocols are purported to reduce time spent on mechanical ventilation. However, evidence supporting their use in clinical practice is inconsistent.

OBJECTIVES: To assess the effects of protocolized weaning from mechanical ventilation on the total duration of mechanical ventilation for critically ill adults; ascertain differences between protocolized and non-protocolized weaning in terms of mortality, adverse events, quality of life, weaning duration, intensive care unit (ICU) and hospital length of stay (LOS); and explore variation in outcomes by type of ICU, type of protocol and approach to delivering the protocol.

SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2010), MEDLINE (1950 to 2010), EMBASE (1988 to 2010), CINAHL (1937 to 2010), LILACS (1982 to 2010), ISI Web of Science and ISI Conference Proceedings (1970 to 2010), Cambridge Scientific Abstracts (inception to 2010) and reference lists of articles. We did not apply language restrictions.

SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials of protocolized weaning versus non-protocolized weaning from mechanical ventilation in critically ill adults.

DATA COLLECTION AND ANALYSIS: Three authors independently assessed trial quality and extracted data. A priori subgroup and sensitivity analyses were performed. We contacted study authors for additional information.

MAIN RESULTS: Eleven trials that included 1971 patients met the inclusion criteria. The total duration of mechanical ventilation geometric mean in the protocolized weaning group was on average reduced by 25% compared with the usual care group (N = 10 trials, 95% CI 9% to 39%, P = 0.006); weaning duration was reduced by 78% (N = 6 trials, 95% CI 31% to 93%, P = 0.009); and ICU LOS by 10% (N = 8 trials, 95% CI 2% to 19%, P = 0.02). There was significant heterogeneity among studies for total duration of mechanical ventilation (I(2) = 76%, P <0.01) and weaning duration (I(2) = 97%, P <0.01), which could not be explained by subgroup analyses based on type of unit or type of approach.

AUTHORS' CONCLUSIONS: There is some evidence of a reduction in the duration of mechanical ventilation, weaning duration and ICU LOS with use of standardized protocols, but there is significant heterogeneity among studies and an insufficient number of studies to investigate the source of this heterogeneity. Although some study authors suggest that organizational context may influence outcomes, these factors were not considered in all included studies and therefore could not be evaluated.

Postoperative pulmonary calcification in a child with truncus arteriosus

Pulmonary calcification is uncommon in children. It is rarely described following cardiac surgery. Here, the authors describe the case of an infant who developed extensive pulmonary calcification following the repair of truncus arteriosus.

Protocolized versus non-protocolized weaning for reducing the duration of invasive mechanical ventilation in critically ill paediatric patients

Background:Mechanical ventilation is a critical component of paediatric intensive care therapy. It is indicated when the patient’s spontaneous ventilation is inadequate to sustain life. Weaning is the gradual reduction of ventilatory support and the transfer of respiratory control back to the patient. Weaning may represent a large proportion of the ventilatory period. Prolonged ventilation is associated with significant morbidity, hospital cost, psychosocial and physical risks to the child and even death. Timely and effective weaning may reduce the duration of mechanical ventilation and may reduce the morbidity and mortality associated with prolonged ventilation. However, no consensus has been reached on criteria that can be used to identify when patients are ready to wean or the best way to achieve it.Objectives:To assess the effects of weaning by protocol on invasively ventilated critically ill children. To compare the total duration of invasive mechanical ventilation of critically ill children who are weaned using protocols versus those weaned through usual (non-protocolized) practice. To ascertain any differences between protocolized weaning and usual care in terms of mortality, adverse events, intensive care unit length of stay and quality of life.Search methods:We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 10, 2012), MEDLINE (1966 to October 2012), EMBASE (1988 to October 2012), CINAHL (1982 to October 2012), ISI Web of Science and LILACS. We identified unpublished data in the Web of Science (1990 to October 2012), ISI Conference Proceedings (1990 to October 2012) and Cambridge Scientific Abstracts (earliest to October 2012). We contacted first authors of studies included in the review to obtain further information on unpublished studies or work in progress. We searched reference lists of all identified studies and review papers for further relevant studies. We applied no language or publication restrictions.Selection criteriaWe included randomized controlled trials comparing protocolized weaning (professional-led or computer-driven) versus non-protocolized weaning practice conducted in children older than 28 days and younger than 18 years.Data collection and analysis:Two review authors independently scanned titles and abstracts identified by electronic searching. Three review authors retrieved and evaluated full-text versions of potentially relevant studies, independently extracted data and assessed risk of bias.Main results:We included three trials at low risk of bias with 321 children in the analysis. Protocolized weaning significantly reduced total ventilation time in the largest trial (260 children) by a mean of 32 hours (95% confidence interval (CI) 8 to 56; P = 0.01). Two other trials (30 and 31 children, respectively) reported non-significant reductions with a mean difference of -88 hours (95% CI -228 to 52; P = 0.2) and -24 hours (95% CI -10 to 58; P = 0.06). Protocolized weaning significantly reduced weaning time in these two smaller trials for a mean reduction of 106 hours (95% CI 28 to 184; P = 0.007) and 21 hours (95% CI 9 to 32; P < 0.001). These studies reported no significant effects for duration of mechanical ventilation before weaning, paediatric intensive care unit (PICU) and hospital length of stay, PICU mortality or adverse events.Authors' conclusions:Limited evidence suggests that weaning protocols reduce the duration of mechanical ventilation, but evidence is inadequate to show whether the achievement of shorter ventilation by protocolized weaning causes children benefit or harm.

Dysfunction of Endothelial Progenitor Cells from Smokers and Chronic Obstructive Pulmonary Disease Patients Due to Increased DNA Damage and Senescence

Cardiovascular disease (CVD) is a major cause of death in smokers, particularly in those with chronic obstructive pulmonary disease (COPD). Circulating endothelial progenitor cells (EPC) are required for endothelial homeostasis, and their dysfunction contributes to CVD. To investigate EPC dysfunction in smokers, we isolated and expanded blood outgrowth endothelial cells (BOEC) from peripheral blood samples from healthy nonsmokers, healthy smokers, and COPD patients. BOEC from smokers and COPD patients showed increased DNA double-strand breaks and senescence compared to nonsmokers. Senescence negatively correlated with the expression and activity of sirtuin-1 (SIRT1), a protein deacetylase that protects against DNA damage and cellular senescence. Inhibition of DNA damage response by silencing of ataxia telangiectasia mutated (ATM) kinase resulted in upregulation of SIRT1 expression and decreased senescence. Treatment of BOEC from COPD patients with the SIRT1 activator resveratrol or an ATM inhibitor (KU-55933) also rescued the senescent phenotype. Using an in vivo mouse model of angiogenesis, we demonstrated that senescent BOEC from COPD patients are dysfunctional, displaying impaired angiogenic ability and increased apoptosis compared to cells from healthy nonsmokers. Therefore, this study identifies epigenetic regulation of DNA damage and senescence as pathogenetic mechanisms linked to endothelial progenitors' dysfunction in smokers and COPD patients. These defects may contribute to vascular disease and cardiovascular events in smokers and could therefore constitute therapeutic targets for intervention. 

The future of antimicrobial therapy in the era of antibiotic resistance in cystic fibrosis pulmonary infection

Cystic fibrosis (CF) is characterised by chronic polymicrobial airway infection and inflammation, which is the major cause of morbidity and mortality. Aggressive use of antimicrobials has been fundamental in increasing the life expectancy of CF patients in recent years. However, enhanced culture and non-culture based detection methods have identified bacteria in the CF lung not previously isolated from CF patients by routine diagnostic microbiology Coupled with increasing antimicrobial resistance, the future of antimicrobial therapy in CF respiratory infection remains challenging. New strategies are needed to address these problems and ensure improvements in life expectancy are maintained. Potential future strategies include the use of new antimicrobial agents and formulations currently in clinical trials, alternative methods of selecting appropriate therapeutic regimens, determination of the pathogenicity of species newly associated with CF and the development of new antimicrobials and adjuvants for use in clinical practice.

Achaete-scute homolog-1 linked to remodeling and preneoplasia of pulmonary epithelium

The basic helix-loop-helix protein achaete-scute homolog-1 (ASH1) is involved in lung neuroendocrine (NE) differentiation and tumor promotion in SV40 transgenic mice. Constitutive expression of human ASH-1 (hASH1) in mouse lung results in hyperplasia and remodeling that mimics bronchiolization of alveoli (BOA), a potentially premalignant lesion of human lung carcinomas. We now show that this is due to sustained cellular proliferation in terminal bronchioles and resistance to apoptosis. Throughout the airway epithelium the expression of anti-apoptotic Bcl-2 and c-Myb was increased and Akt/mTOR pathway activated. Moreover, the expression of matrix metalloproteases (MMPs) including MMP7 was specifically enhanced at the bronchiolo-alveolar duct junction and BOA suggesting that MMPs play a key role in this microenvironment during remodeling. We also detected MMP7 in 70% of human BOA lesions. Knockdown of hASH1 gene in human lung cancer cells in vitro suppressed growth by increasing apoptosis. We also show that forced expression of hASH1 in immortalized human bronchial epithelial cells decreases apoptosis. We conclude that the impact of hASH1 is not limited to cells with NE phenotype. Rather, constitutive expression of hASH1 in lung epithelium promotes remodeling through multiple pathways that are commonly activated during lung carcinogenesis. The collective results suggest a novel model of BOA formation via hASH1-induced suppression of the apoptotic pathway. Our study yields a promising new preclinical tool for chemoprevention of peripheral lung carcinomas. © 2007 USCAP, Inc All rights reserved.

Pepsin in bronchoalveolar lavage fluid:a specific and sensitive method of diagnosing gastro-oesophageal reflux-related pulmonary aspiration

Gastro-oesophageal reflux (GOR)-related aspiration is associated with respiratory disease, but the current "gold standard" investigation, the lipid-laden macrophage index (LLMI), is flawed. A specific marker of GOR-related aspiration should originate in the stomach, but not the lung. An assay to detect gastric pepsin in the bronchoalveolar lavage (BAL) of children was developed and validated.

Weaning from mechanical ventilation: a scoping review of qualitative studies

Background; Weaning from mechanical ventilation is influenced by patient, clinician, and organizational factors.

Objective: To identify factors that may influence weaning and adoption of weaning strategies and tools, clinicians’ perceptions of weaning strategies, and weaning experiences of patients and patients’ families.

Method: A scoping review of indexed and nonindexed publications (1990–2012) was done. Qualitative studies of health care providers, patients, and patients’ families involved in weaning were included. Two investigators independently screened 8350 publications and extracted data from 43 studies. Study themes were content analyzed to identify common categories and themes within the categories.

Results: The study sample consisted of nurses in 15 studies, nurses and patients in 1 study, various health care providers in 11, patients in 10, and physicians in 4. Categories identified were as follows: for nurses, role or scope of practice, informing decision making, and influence on weaning outcome; for health care providers, factors influencing weaning decisions or use of protocols, role or scope of practice related to weaning, and organizational structure or practice environment; for patients, experience of mechanical ventilation and weaning, experience of the intensive care environment, psychological phenomena, and enabling success in weaning; and for physicians, tools or factors to facilitate weaning decisions and perceptions of nurses’ role and scope of practice.

Conclusions: Important issues identified were perceived importance of interprofessional collaboration and communication, need to combine subjective knowledge of the patient with objective clinical data, balancing of weaning systematization with individual needs, and appreciation of the physical and psychological work of weaning.