Transcriptome analysis and safety profile of the early-phase clinical response to an adjuvanted grass allergoid immunotherapy.

Background: Specific immunotherapy is the only type of disease-modifying treatment, which induces rapid desensitization and long-term sustained unresponsiveness in patients with seasonal allergic rhinoconjunctivitis. The safety and tolerability of a new cumulative dose regimen of 35600 SU Grass MATA MPL for subcutaneous immunotherapy were assessed in pre-seasonal, single-blind, placebo controlled Phase I clinical study. Underlying immunological mechanisms were explored using transcriptome analysis of peripheral blood mononuclear cells.

Strong dose response after immunotherapy with PQ grass using conjunctival provocation testing.

Background: Pollinex Quattro Grass (PQ Grass) is an effective, well-tolerated, short pre-seasonal subcutaneous immunotherapy to treat seasonal allergic rhinoconjunctivitis (SAR) due to grass pollen. In this Phase II study, 4 cumulative doses of PQ Grass and placebo were evaluated to determine its optimal cumulative dose.

Methods: Patients with grass pollen-induced SAR were randomised to either a cumulative dose of PQ Grass (5100, 14400, 27600 and 35600 SU) or placebo, administered as 6 weekly subcutaneous injections over 31-41 days (EudraCT number 2017-000333-31).

U-BIOPRED: evaluation of the value of a public-private partnership to industry.

Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) was initiated in the first year of the Innovative Medicines Initiative (IMI). It was an ambitious plan to tackle the understanding of asthma through an integration of clinical and multi-'omics approaches that necessitated the bringing together of industry, academic, and patient representatives because it was too large to be managed by any one of the partners in isolation. It was a novel experience for all concerned.

Randomized controlled trials define shape of dose response for Pollinex Quattro Birch allergoid immunotherapy.

Background: The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed 2 phase II studies to determine its optimal cumulative dose.

Breathomics for Assessing the Effects of Treatment and Withdrawal With Inhaled Beclomethasone/Formoterol in Patients With COPD.

Prospective pharmacological studies on breathomics profiles in COPD patients have not been previously reported. We assessed the effects of treatment and withdrawal of an extrafine inhaled corticosteroid (ICS)-long-acting β-agonist (LABA) fixed dose combination (FDC) using a multidimensional classification model including breathomics. A pilot, proof-of-concept, pharmacological study was undertaken in 14 COPD patients on maintenance treatment with inhaled fluticasone propionate/salmeterol (500/50 μg b.

Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort.

U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.

A trial of beclomethasone/formoterol in COPD using EXACT-PRO to measure exacerbations.

Combination inhalers containing corticosteroids and long-acting β-agonists are used to reduce exacerbation rates in patients with severe chronic obstructive pulmonary disease (COPD). The FORWARD (Foster 48-week Trial to Reduce Exacerbations in COPD) clinical trial in severe COPD patients is a comparison of extrafine beclomethasone dipropionate and formoterol in a combination inhaler with extrafine formoterol; the co-primary end-points are exacerbation rates over 48 weeks and improvement in forced expiratory volume in 1 s over 12 weeks. The traditional physician diagnosis of exacerbations is a co-primary outcome, and the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) means of collecting patient-reported outcome data are also being used to enhance the detection of exacerbation events.

Proteomic biomarkers for acute interstitial lung disease in gefitinib-treated Japanese lung cancer patients.

Interstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan.

The Christmas season as a risk factor for chronic obstructive pulmonary disease exacerbations.

Background: Epidemics of hospitalization for chronic obstructive pulmonary disease (COPD) occur annually during the Christmas holidays, and COPD exacerbations commonly coincide with respiratory viral infections.

Objective: To compare the incidence and determinants of COPD exacerbations occurring between the Christmas holiday period and the remainder of the winter season.

Methods: Seventy-one subjects with COPD of mixed severity faxed daily symptom diaries to a computer monitoring system from December 1, 2006, to April 30, 2007.

Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study.

Rationale: Interstitial lung disease (ILD) occurs in Japanese patients with non-small cell lung cancer (NSCLC) receiving gefitinib.

Objectives: To elucidate risk factors for ILD in Japanese patients with NSCLC during treatment with gefitinib or chemotherapy.

Methods: In a prospective epidemiologic cohort, 3,166 Japanese patients with advanced/recurrent NSCLC were followed for 12 weeks on 250 mg gefitinib (n = 1,872 treatment periods) or chemotherapy (n = 2,551).

Quantifying of severity of exacerbations in chronic obstructive pulmonary disease: adaptations to the definition to allow quantification.

Exacerbations of chronic obstructive pulmonary disease (COPD) offer a considerable clinical challenge for clinical practice and drug development. The underlying pathobiology of these characteristic events is unclear. We are far behind other disease areas, such as cardiology, where there are effective approaches for diagnosing and managing acute and potentially fatal events.

Exacerbation-free COPD: a goal too far?

The seventh Lund COPD workshop focused on exacerbations. As chronic obstructive pulmonary disease (COPD) progresses, exacerbations, events characterized by acute worsening of symptoms, increase in frequency and severity. Patients fear their occurrence, as they compromise function and quality of life, may require admission to the hospital, and can be fatal.

Interaction between smoking and genetic factors in the development of chronic bronchitis.

Rationale: Smoking is a primary risk factor for chronic bronchitis, emphysema, and chronic obstructive pulmonary disease, but since not all smokers develop disease, it has been suggested that some individuals may be more susceptible to exogenous factors, such as smoking, and that this susceptibility could be genetically determined.

Objectives: The aim of the present study was to assess, in a population-based sample of twins, the following: (1) to what extent genetic factors contribute to the development of chronic bronchitis, including emphysema, taking sex into consideration, and (2) whether the genetic influences on chronic bronchitis, including emphysema, are separate from those for smoking behavior.

Methods: Disease cases and smoking habits were identified in 44,919 twins older than 40 years from the Swedish Twin Registry.

Developments in inhaled immunosuppressive therapy for the prevention of pulmonary graft rejection.

Cyclosporin is the main immunosuppressive treatment for lung and heart-lung transplantation. When combined with azathioprine and oral corticosteroids, repeated episodes of acute rejection are limited to a minority of transplant patients. Despite early successful transplantation, many patients developed a disabling and fatal condition called obliterative bronchiolitis.

Personalized medicine and proteomics: lessons from non-small cell lung cancer.

Personalized medicine allows the selection of treatments best suited to an individual patient and disease phenotype. To implement personalized medicine, effective tests predictive of response to treatment or susceptibility to adverse events are needed, and to develop a personalized medicine test, both high quality samples and reliable data are required. We review key features of state-of-the-art proteomic profiling and introduce further analytic developments to build a proteomic toolkit for use in personalized medicine approaches.

Conservation of whole body nitric oxide metabolism in human alcoholic liver disease: implications for nitric oxide production.

Objective: Patients with advanced liver diseases tend to develop a hyperdynamic circulation which complicates cirrhosis. Impairment of nitric oxide (NO) metabolism has been implicated in the pathogenesis of portal hypertension. The aim of this study was to determine nitric oxide synthase (NOS)-dependent whole body NO production in patients with decompensated liver cirrhosis and portal hypertension.

Relationship between respiratory symptoms and medical treatment in exacerbations of COPD.

Exacerbations of chronic obstructive pulmonary disease (COPD) can be defined symptomatically or by healthcare contacts, yet the relationship between these events is unknown. Data were collected during a 1-yr study of the budesonide/formoterol combination in COPD patients, where exacerbations, defined by increases in treatment, were compared with daily records of respiratory symptoms, rescue medication use and peak expiratory flow (PEF). The relationship between changes in these variables and the medical event was examined using different modelling approaches.

Pulmonary hypertension and chronic obstructive pulmonary disease: a case for treatment.

Current pharmacotherapy for chronic obstructive pulmonary disease (COPD) relieves symptoms and reduces exacerbation through improving airflow limitation. Such drugs do not effectively improve exercise tolerance due in part to pulmonary hypertension associated with severe COPD, nor impact on its increased morbidity and mortality. Exercise intolerance is often improved (temporarily) by lung volume reduction surgery and pulmonary rehabilitation.