Prospective observational study in patients with obstructive lung disease : NOVELTY design

Peer reviewedPublisher PD

Breathomics can discriminate between anti IgE-treated and non-treated severe asthma adults

Rationale: Omalizumab, an anti-IgE monoclonal antibody, is indicated in adults with severe persistent allergic asthma. Exhaled molecular markers can provide phenotypic information in asthma. Objectives: Determine whether adults with severe asthma on omalizumab (anti-IgE+) have a different breathprint compared with those who were not on anti-IgE therapy (anti-IgE-) as assessed by eNoses and gas chromatography/mass spectrometry (GC/MS) (breathomics). Methods: This was a cross-sectional analysis of the U- BIOPRED adult cohort. Severe asthma was defined by IMI-criteria [Bel, Thorax 2011]. Anti-IgE+ patients were on a regular treatment with s.c. omalizumab (150-375 mg) every 2-4 weeks. Exhaled volatile compounds trapped on adsorption tubes were analysed by a centralized eNose platform (Owlstone Lonestar, two Cyranose 320, Comon Invent, Tor Vergata TEN), including a total of 190 sensors, and GC/MS. Recursive feature elimination (http://topepo.github.io/caret/rfe.html) was used for feature selection and random forests, more robust to overfitting, for classification. Results: 9 anti- IgE+ (females/males 2/7, age 52.6±16.3 years, mean±SD, 1/2/6 current/ex/nonsmokers, pre-bronchodilator FEV1 70.6±21.1% predicted value) and 30 anti-IgE- patients (18/12 females/males, age 53.2±14.2 years, 0/16/14 current/ex/nonsmokers, pre-bronchodilator FEV1 59.6±30.7% predicted value) were studied. Conclusions: Preliminary results suggest that breathomics can distinguish between anti-IgE+ and anti-IgE- severe asthma patients

What bothers severe asthma patients most? A paired patient-clinician study across seven European countries

Introduction: Severe asthma is a complex, multi-dimensional disease. Optimal treatment adherence and outcomes require shared decision-making, rooted in mutual understanding between patient and clinician. This study used a novel, patient-centred approach to examine the most bothersome aspects of severe asthma to patients, as seen from both perspectives in asthma registries. Methods: Across seven countries, 126 patients with severe asthma completed an open-ended survey regarding most bothersome aspect(s) of their asthma. Patients’ responses were linked with their treating clinician who also completed free-text survey about each patient's most bothersome aspect(s). Responses were coded using content analysis, and patient and clinician responses were compared. Finally, asthma registries that are part of the SHARP Clinical Research Collaboration were examined to see the extent to which they reflected the most bothersome aspects reported by patients. Results: Eighty-eight codes and 10 themes were identified. Clinicians were more focused on direct physical symptoms and were less focused on ‘holistic’ aspects such as the effort required to self-manage their disease. Clinicians accurately identified a most bothersome symptom for 29% of patients. Agreement was particularly low in younger patients and those infrequently using oral corticosteroids. In asthma registries, patient aspects were predominantly represented in questionnaires. Conclusions: Results demonstrated different perspectives and priorities between patients and clinicians, with clinicians more focused on physical aspects. These differences must be considered when treating individual patients, and within multi-disciplinary treatment teams. The use of questionnaires that include multi-faceted aspects of disease may result in improved asthma research

Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort

Background: Exacerbation-prone asthma is a feature of severe disease. Yet, the basis for its persistency remains unclear. Objectives: To determine the clinical and transcriptomic features of the frequent-exacerbator (FE) and of persistent FEs (PFE) in U-BIOPRED cohort. Methods: We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat ≥2 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures. Results: Of 317 patients, 62.4 % were FE of whom 63.6% were PFE, while 37.6% were IE of whom 61.3% were PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE with eczema, short-acting beta-agonist use and asthma control index. CEA Cell Adhesion Molecule 5 (CEACAM5) was the only differentially-expressed transcript in bronchial biopsies between PE and IE. There were no differentially-expressed genes in the other 4 compartments. There were higher expression scores for Type 2 , T-helper type-17 and Type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while higher expression scores of Type 2, Type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE. Conclusion: FE group and its PFE subgroup are associated with poor asthma control while expressing higher Type 1 and Type 2 activation pathways compared to IE and PIE, respectively

Deep phenotyping and genomic data from a nationally representative study on dementia in India

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.Peer reviewe

Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study

The U-BIOPRED study is a multicentre European study aimed at a better understanding of severe asthma. It included three steroid-treated adult asthma groups (severe nonsmokers (SAn group), severe current/ex-smokers (SAs/ex group) and those with mild–moderate disease (MMA group)) and healthy controls (HC group). The aim of this cross-sectional, bronchoscopy substudy was to compare bronchial immunopathology between these groups. In 158 participants, bronchial biopsies and bronchial epithelial brushings were collected for immunopathologic and transcriptomic analysis. Immunohistochemical analysis of glycol methacrylate resin-embedded biopsies showed there were more mast cells in submucosa of the HC group (33.6 mm⁻ ²) compared with both severe asthma groups (SAn: 17.4 mm⁻ ², p<0.001; SAs/ex: 22.2 mm⁻ ², p=0.01) and with the MMA group (21.2 mm⁻ ², p=0.01). The number of CD4+ lymphocytes was decreased in the SAs/ex group (4.7 mm⁻ ²) compared with the SAn (11.6 mm⁻ ², p=0.002), MMA (10.1 mm⁻ ², p=0.008) and HC (10.6 mm⁻ ², p<0.001) groups. No other differences were observed. Affymetrix microarray analysis identified seven probe sets in the bronchial brushing samples that had a positive relationship with submucosal eosinophils. These mapped to COX-2 (cyclo-oxygenase-2), ADAM-7 (disintegrin and metalloproteinase domain-containing protein 7), SLCO1A2 (solute carrier organic anion transporter family member 1A2), TMEFF2 (transmembrane protein with epidermal growth factor like and two follistatin like domains 2) and TRPM-1 (transient receptor potential cation channel subfamily M member 1); the remaining two are unnamed. We conclude that in nonsmoking and smoking patients on currently recommended therapy, severe asthma exists despite suppressed tissue inflammation within the proximal airway wall

Treatable traits in the European U-BIOPRED adult asthma cohorts

Letter to the edito

Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma

A proportion of severe asthma patients suffers from persistent airflow limitation (PAL), often associated with more symptoms and exacerbations. Little is known about the underlying mechanisms. Here, our aim was to discover unexplored potential mechanisms using Gene Set Variation Analysis (GSVA), a sensitive technique that can detect underlying pathways in heterogeneous samples. Severe asthma patients from the U-BIOPRED cohort with PAL (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal) were compared with those without PAL. Gene expression was assessed on the total RNA of sputum cells, nasal brushings, and endobronchial brushings and biopsies. GSVA was applied to identify differentially enriched predefined gene signatures based on all available gene expression publications and data on airways disease. Differentially enriched gene signatures were identified in nasal brushings (n=1), sputum (n=9), bronchial brushings (n=1) and bronchial biopsies (n=4) that were associated with response to inhaled steroids, eosinophils, interleukin-13, interferon-α, specific CD4+ T-cells and airway remodelling. PAL in severe asthma has distinguishable underlying gene networks that are associated with treatment, inflammatory pathways and airway remodelling. These findings point towards targets for the therapy of PAL in severe asthma

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good