The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.

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Cochrane Handbook for Systematic Reviews of Interventions

Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

https://www.who.int/respiratory/copd/GOLD_WR_06.pdf

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.

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The UK Biobank resource with deep phenotyping and genomic data

An earlier version (version 5.0.2, 2008) of the Handbook is also published by John Wiley & Sons, Ltd under “The Cochrane Book Series” Imprint, as Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions (ISBN 978-0470057964) by John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England, Telephone (+44) 1243 779777; Email (for orders and customer service enquiries): cs-books@wiley.co.uk. Visit their Home Page on www.wiley.com.

Chapter 8: Assessing risk of bias in included studies

Assessing Risk of Bias in Included Studies

Background: Eosinophilic airway inflammation and airway remodelling are characteristic features of asthma, but the association between them is unknown. Aim: To test the hypothesis that blood eosinophil counts would be associated with the development of airflow obstruction in a population-based cohort of 1037 young adults. Methods: Blood eosinophils and spirometry were measured at ages 21, 26, 32, and 38 years. Associations between spirometry and eosinophil counts were analysed using linear mixed models with fixed effects for age and random effects for participants to accommodate repeated measures, with adjustment for sex, cumulative tobacco smoking, childhood and adult asthma, and spirometric measures at age 18. We further analysed associations between mean eosinophil counts and changes in spirometry from ages 21 to 38 years. Results: Higher eosinophils were associated with lower FEV1/FVC ratios and lower percent-predicted FEV1 values for both pre- and post-bronchodilator spirometry (p values Conclusions: Blood eosinophil counts are associated with airflow obstruction independently of asthma and smoking. Higher eosinophil counts are associated with enhanced declines in lung function and increasing airflow obstruction from age 21 to 38 suggesting that eosinophilia is a risk factor for developing progressive airflow obstruction even in those without respiratory disease or symptoms.

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Blood eosinophils and lung function decline in young adults

Repeatabilty of capsaicin cough reflex sensitivity measurement

Mepolizumab reduces circulating and airway eosinophils in severe eosinophilic asthma. The response to corticosteroids in asthma is related to the presence of eosinophilic airways inflammation. We have tested the hypothesis that mepolizumab treatment is associated with a reduced response to oral corticosteroids in patients with severe eosinophilic asthma. Methods: A randomised controlled trial of mepolizumab in severe asthma was conducted as previously described (Haldar et al, NEJM 2009 360:973-984). Subjects in the mepolizumab arm had 2 weeks of oral prednisolone treatment (0.5mg/kg) prior to receiving mepolizumab, and at the end of the 12 month treatment period whilst on mepolizumab. Spirometry, Asthma Control Questionnaire 5 (ACQ5) and visual analogue scale (VAS) for cough, breathlessness and wheeze were measured before and each course of prednisolone. Paired t-tests were used to compare the change in each measure before and on mepolizumab treatment. Results: 28 subjects were evaluated. Prednisolone was associated with a significant greater improvement in mean VAS prior to mepolizumab compared to on mepolizumab. There was no significant change in FEV1 and ACQ5 (table). Conclusion: Treatment with mepolizumab is associated with an attenuated symptom response to prednisolone treatment in severe eosinophilic asthma via a mechanism that is likely to be independent of changes in airflow limitation.

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Mepolizumab and the response to oral prednisolone in patients with severe eosinophilic asthma

Overlapping biologic exacerbation clusters in asthma and chronic obstructive pulmonary disease have distinct sputum mediator and microbiome profiles

We read with interest the study by Palmer and colleagues.1 Their findings suggest that patients who are Arg/Arg homozygous at position 16 of the β2 adrenoceptor may be at increased risk of asthma exacerbations, particularly when treated with inhaled salmeterol. These results add to the body of evidence questioning the safety of long-acting β2 agonists in this subgroup of …

https://thorax.bmj.com/content/thoraxjnl/63/6/568.4.full.pdf

Ian D. Pavord

Papers

Blood eosinophils and lung function decline in young adults

Repeatabilty of capsaicin cough reflex sensitivity measurement

Mepolizumab and the response to oral prednisolone in patients with severe eosinophilic asthma

Overlapping biologic exacerbation clusters in asthma and chronic obstructive pulmonary disease have distinct sputum mediator and microbiome profiles

Use of long-acting β2 agonists in arginine-16 homozygous patients with asthma