Current and future therapies for Pseudomonas aeruginosa infection in patients with cystic fibrosis.

Pseudomonas aeruginosa opportunistically infects the airways of patients with cystic fibrosis and causes significant morbidity and mortality. Initial infection can often be eradicated though requires prompt detection and adequate treatment. Intermittent and then chronic infection occurs in the majority of patients.

Danger-recognizing proteins, β-defensin-128 and histatin-3, as potential biomarkers of recurrent coronary events.

Conventional risk factors have limited ability to predict recurrent events in subjects with first-time coronary artery disease (CAD). This aim of this study was to identify novel biomarkers using comparative global proteome analysis to improve the risk assessment for recurrent coronary events. We used samples from phase-I of the Indian Atherosclerosis Research Study (IARS), consisting of 2,332 subjects, of whom 772 were CAD-affected subjects, including 152 with recurrent events identified during a 5-year follow-up period.

Age at menarche and lung function: a Mendelian randomization study.

A trend towards earlier menarche in women has been associated with childhood factors (e.g. obesity) and hypothesised environmental exposures (e.

Heterozygous mice reveal novel roles for the planar cell polarity pathway in adult lung homeostasis and repair.

Lung diseases impose a huge economic and health burden worldwide. A key aspect of several adult lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), including emphysema, is aberrant tissue repair, which leads to an accumulation of damage and impaired respiratory function. Currently, there are few effective treatments available for these diseases and their incidence is rising.

X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3.

By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2-DNAAF4-HSP90 complex akin to the HSP90 co-chaperone R2TP complex.

Is fruit and vegetable intake associated with asthma or chronic rhino-sinusitis in European adults? Results from the Global Allergy and Asthma Network of Excellence (GALEN) Survey.

Background: Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases.

Objective: We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults.

Methods: A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GALEN) screening survey, in which 55,000 adults aged 15-75 answered a questionnaire on respiratory symptoms.

Occupational self-coding and automatic recording (OSCAR): a novel web-based tool to collect and code lifetime job histories in large population-based studies.

Objectives The standard approach to the assessment of occupational exposures is through the manual collection and coding of job histories. This method is time-consuming and costly and makes it potentially unfeasible to perform high quality analyses on occupational exposures in large population-based studies. Our aim was to develop a novel, efficient web-based tool to collect and code lifetime job histories in the UK Biobank, a population-based cohort of over 500 000 participants.

Chronic obstructive pulmonary disease in Welsh slate miners.

Background: Exposure to respirable crystalline silica (RCS) causes emphysema, airflow limitation and chronic obstructive pulmonary disease (COPD). Slate miners are exposed to slate dust containing RCS but their COPD risk has not previously been studied.

Aims: To study the cumulative effect of mining on lung function and risk of COPD in a cohort of Welsh slate miners and whether these were independent of smoking and pneumoconiosis.

Changes in symptoms of asthma and rhinitis by sensitization status over ten years in a cohort of young Chilean adults.

Background: We investigated the net changes in prevalence of symptoms of asthma and rhinitis over 10 years in a cohort of young by baseline sensitization status.

Methods: One thousand one hundred ninety three Chilean adults subjects aged 22-28 living in a semi-rural area of central Chile answered a lifestyle and the European Community Respiratory Health Survey (ECRHS) questionnaires. Bronchial hyper-responsiveness (BHR) and skin prick test (SPT) to eight allergens were measured at baseline in 2001.

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

Aims: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year.

Methods And Results: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy.

Dietary intake and risk of asthma in children and adults: protocol for a systematic review and meta-analysis.

Background: Diet has been proposed to modulate the risk of asthma in children and adults. An increasing body of epidemiological studies have been published in the last year investigating the association between dietary intake and asthma. As part of the Evidence-Based Clinical Practice Guideline Task Force on 'Lifestyle Interventions in Allergy and Asthma' funded by the European Academy of Allergy and Clinical Immunology, we will use a systematic approach to review the evidence from published scientific literature on dietary intake and asthma in children and adults.

Impact of Macrophages in Atherosclerosis.

Atherosclerosis is driven by inflammation, with a strong involvement of innate immunity, and involves an expansion of the arterial intima, a normally small area composed of several cell types including smooth muscle cells, lipids, monocytes, macrophages, dendritic cells, and extracellular matrix. Macrophages derived from recruited monocytes are predominant innate immune cells that play crucial roles in the formation of atherosclerotic lesions. Human atherosclerotic plaques have shown that macrophage subsets within a plaque might be more useful for explaining plaque phenotype than just simply giving the total number of macrophages.

SAPHO Syndrome: Current Developments and Approaches to Clinical Treatment.

SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a rare autoimmune disease which, due to its clinical presentation and symptoms, is often misdiagnosed and unrecognized. Its main features are prominent inflammatory cutaneous and articular manifestations. Treatments with immunosuppressive drugs have been used for the management of SAPHO with variable results.

Chronic obstructive pulmonary disease and acute myocardial infarction: effects on presentation, management, and outcomes.

Cardiovascular disease is a common cause of death in patients with chronic obstructive pulmonary disease (COPD) and is a key target for improving outcomes. However, there are concerns that patients with COPD may not have enjoyed the same mortality reductions from acute myocardial infarction (AMI) in recent decades as the general population. This has raised questions about differences in presentation, management and outcomes in COPD patients compared to non-COPD patients.

Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis.

Objective: To determine whether feeding infants with hydrolysed formula reduces their risk of allergic or autoimmune disease.

Design: Systematic review and meta-analysis, as part of a series of systematic reviews commissioned by the UK Food Standards Agency to inform guidelines on infant feeding. Two authors selected studies by consensus, independently extracted data, and assessed the quality of included studies using the Cochrane risk of bias tool.

Qualitative European survey of patients with idiopathic pulmonary fibrosis: patients' perspectives of the disease and treatment.

Background: 'Living with IPF and an exploration of Esbriet® - a new treatment' was an exploratory, qualitative, real-world survey of European patients with idiopathic pulmonary fibrosis (IPF) who were receiving treatment with pirfenidone prior to its commercial availability. The aim of the survey was to probe the impact of IPF on patients' quality of life; the role of healthcare professionals and caregivers; the information needs of both patients and their caregivers; and patients' perceptions of pirfenidone as a new treatment option for IPF.

Methods: Patients from the UK, Germany and Italy, with a diagnosis of IPF (duration >3 months), who were being treated with pirfenidone, were recruited from patient support groups, specialist centres and advocacy groups.

Essential Roles of Toll-Like Receptors in Atherosclerosis.

Atherosclerosis is driven by inflammation with an involvement of innate and adaptive immune responses. Toll-like receptors, the well-defined pattern recognition receptors of the immune system, play a central role in macrophage activation. Toll-like receptors recognize pathogen-associated molecular patterns expressed by a wide range of infectious agents and provide a strong link between local innate and adaptive immunity.

The role of interleukin 35 in atherosclerosis.

Atherosclerosis has been widely recognized as a slow progressing inflammatory disease of the arterial walls involving both inflammation and autoimmune processes with a complex etiology in which the immune system plays a key role. A hallmark of atherosclerosis is that the macrophages pick up the lipids to form the foam cells which build up the plaque in the arterial wall. Consequently, the arteries become narrowed.

Laboratory Animal Allergy in the Modern Era.

Laboratory animal workers face a high risk of developing laboratory animal allergy as a consequence of inhaling animal proteins at work; this has serious consequences for their health and future employment. Exposure to animal allergen remains to be the greatest risk factor although the relationship is complex, with attenuation at high allergen exposure. Recent evidence suggests that this may be due to a form of natural immunotolerance.

Ex Vivo and In Vivo Lentivirus-Mediated Transduction of Airway Epithelial Progenitor Cells.

A key challenge in pulmonary gene therapy for cystic fibrosis is to provide long-term correction of the genetic defect. This may be achievable by targeting airway epithelial stem/progenitor cells with an integrating vector. Here, we evaluated the ability of a lentiviral vector, derived from the simian immunodeficiency virus and pseudotyped with F and HN envelope proteins from Sendai virus, to transduce progenitor basal cells of the mouse nasal airways.

A new spirometry-based algorithm to predict occupational pulmonary restrictive impairment.

Background: Spirometry is often included in workplace-based respiratory surveillance programmes but its performance in the identification of restrictive lung disease is poor, especially when the prevalence of this condition is low in the tested population.

Aims: To improve the specificity (Sp) and positive predictive value (PPV) of current spirometry-based algorithms in the diagnosis of restrictive pulmonary impairment in the workplace and to reduce the proportion of false positives findings and, as a result, unnecessary referrals for lung volume measurements.

Methods: We re-analysed two studies of hospital patients, respectively used to derive and validate a recommended spirometry-based algorithm [forced vital capacity (FVC) < 85% predicted and forced expiratory volume in 1 s (FEV1)/FVC > 55%] for the recognition of restrictive pulmonary impairment.

The need for patient-centred clinical research in idiopathic pulmonary fibrosis.

Patient-centredness is an accepted term and is perceived by healthcare professionals to be morally and ethically desirable. We are motivated by the belief that this approach will improve the patient-professional experience of the decision-making process and improve health outcomes. We acknowledge that patients, either as participants or as co-investigators, have positive contributions to make to research.

Development of an international scale of socio-economic position based on household assets.

Background: The importance of studying associations between socio-economic position and health has often been highlighted. Previous studies have linked the prevalence and severity of lung disease with national wealth and with socio-economic position within some countries but there has been no systematic evaluation of the association between lung function and poverty at the individual level on a global scale. The BOLD study has collected data on lung function for individuals in a wide range of countries, however a barrier to relating this to personal socio-economic position is the need for a suitable measure to compare individuals within and between countries.