Predictors of exacerbations in chronic obstructive pulmonary disease - results from the Bergen COPD Cohort Study

Background: COPD exacerbations accelerate disease progression. Aims To examine if COPD characteristics and systemic inflammatory markers predict the risk for acute COPD exacerbation (AECOPD) frequency and duration. Methods: 403 COPD patients, GOLD stage II-IV, aged 44–76 years were included in the Bergen COPD Cohort Study in 2006/07, and followed for 3 years. Examined baseline predictors were sex, age, body composition, smoking, AECOPD the last year, GOLD stage, Charlson comorbidity score (CCS), hypoxemia (PaO21 AECOPD last year before baseline [1.65 (1.24–2.21)], GOLD III [1.36 (1.07–1.74)], GOLD IV [2.90 (1.98–4.25)], chronic cough [1.64 (1.30–2.06)] and use of inhaled steroids [1.57 (1.21–2.05)]. For AECOPD duration more than three weeks, significant predictors after adjustment were: hypoxemia [0.60 (0.39–0.92)], years since inclusion [1.19 (1.03–1.37)], AECOPD severity; moderate [OR 1.58 (1.14–2.18)] and severe [2.34 (1.58–3.49)], season; winter [1.51 (1.08–2.12)], spring [1.45 (1.02–2.05)] and sTNF-R1 per SD increase [1.16 (1.00–1.35)]. Conclusion: Several COPD characteristics were independent predictors of both AECOPD frequency and duration.publishedVersio

Protected sampling is preferable in bronchoscopic studies of the airway microbiome

The aim was to evaluate susceptibility of oropharyngeal contamination with various bronchoscopic sampling techniques. 67 patients with obstructive lung disease and 58 control subjects underwent bronchoscopy with small-volume lavage (SVL) through the working channel, protected bronchoalveolar lavage (PBAL) and bilateral protected specimen brush (PSB) sampling. Subjects also provided an oral wash (OW) sample, and negative control samples were gathered for each bronchoscopy procedure. DNA encoding bacterial 16S ribosomal RNA was sequenced and bioinformatically processed to cluster into operational taxonomic units (OTU), assign taxonomy and obtain measures of diversity. The proportion of Proteobacteria increased, whereas Firmicutes diminished in the order OW, SVL, PBAL, PSB (p<0.01). The alpha-diversity decreased in the same order (p<0.01). Also, beta-diversity varied by sampling method (p<0.01), and visualisation of principal coordinates analyses indicated that differences in diversity were smaller between OW and SVL and OW and PBAL samples than for OW and the PSB samples. The order of sampling (left versus right first) did not influence alpha- or beta-diversity for PSB samples. Studies of the airway microbiota need to address the potential for oropharyngeal contamination, and protected sampling might represent an acceptable measure to minimise this problem.publishedVersio

Incidence of utilization- and symptom-defined COPD exacerbations in hospital- and population-recruited patients

Objectives: The objectives of this study were to estimate the impact of recruitment source and outcome definition on the incidence of acute exacerbations of COPD (AECOPD) and explore possible predictors of AECOPD. Patients and methods: During a 1-year follow-up, we performed a baseline visit and four telephone interviews of 81 COPD patients and 132 controls recruited from a population-based survey and 205 hospital-recruited COPD patients. Both a definition based on health care utilization and a symptom-based definition of AECOPD were applied. For multivariate analyses, we chose a negative binomial regression model. Results: COPD patients from the population- and hospital-based samples experienced on average 0.4 utilization-defined and 2.9 symptom-defined versus 1.0 and 5.9 annual exacerbations, respectively. The incidence rate ratios for utilization-defined AECOPD were 2.45 (95% CI 1.22–4.95), 3.43 (95% CI 1.59–7.38), and 5.67 (95% CI 2.58–12.48) with Global Initiative on Obstructive Lung Disease spirometric stages II, III, and IV, respectively. The corresponding incidence rate ratios for the symptom-based definition were 3.08 (95% CI 1.96–4.84), 3.45 (95% CI 1.92–6.18), and 4.00 (95% CI 2.09–7.66). Maintenance therapy (regular long-acting muscarinic antagonists, long-acting beta-2 agonists, inhaled corticosteroids, or theophylline) also increased the risk of AECOPD with both exacerbation definitions (incidence rate ratios 1.65 and 1.73, respectively). The risk of AECOPD was 59%–78% higher in the hospital sample than in the population sample. Conclusion: If externally valid conclusions are to be made regarding incidence and predictors of AECOPD, studies should be based on general population samples or adjustments should be made on account of a likely higher incidence in other samples. Likewise, the effect of different AECOPD definitions should be taken into consideration

Participation in research bronchoscopy: a literature review

Bronchoscopy is the preferred method for collecting biological samples from the lower airways of subjects in clinical research. However, ensuring participation in clinical research can be challenging when the research includes an invasive procedure. For this report we reviewed the literature to look for information on participation in research bronchoscopy studies to better design our own study, the Bergen COPD Microbiome study (MicroCOPD). We performed a systematic literature search on participation in research bronchoscopy studies in February 2014 using the search engines of PubMed and EMBASE. The literature search resulted in seven relevant papers. Motivation was an end point in six of the seven papers, but reasons for declining participation and recruitment strategies also seemed important. Human subjects participate in research bronchoscopy studies for personal benefit and altruistic reasons. Inconvenience associated with research, in addition to fear of procedures, is considered a barrier. Radio, especially news stations, generated the most inquiries for a clinical study involving bronchoscopy. There is a lack of information on participation in research bronchoscopy studies in the literature. A bronchoscopy study has been initiated at Haukeland University Hospital, Bergen, Norway, to examine the role of the microbiome in COPD, and participation will be explored as a substudy

Data from: Comparing microbiota profiles in induced and spontaneous sputum samples in COPD patients

Background: Induced and spontaneous sputum are used to evaluate the airways microbiota. Whether the sputum types can be used interchangeably in microbiota research is unknown. Our aim was to compare microbiota in induced and spontaneous sputum from COPD patients sampled during the same consultation. Methods: COPD patients from Bergen, Norway, were followed between 2006/2010, examined during the stable state and exacerbations. 30 patients delivered 36 sample pairs. DNA was extracted by enzymatic and mechanical lysis methods. The V3-V4 region of the 16S rRNA gene was PCR-amplified and prepared for paired-end sequencing. Illumina Miseq System was used for sequencing, and Quantitative Insights Into Microbial Ecology (QIIME) and Stata were used for bioinformatics and statistical analyses. Results: Approximately 4 million sequences were sorted into 1004 different OTUs and further assigned to 106 different taxa. Pair-wise comparison of both taxonomic composition and beta-diversity revealed significant differences in one or both parameters in 1/3 of sample pairs. Alpha-diversity did not differ. Comparing abundances for each taxa identified, showed statistically significant differences between the mean abundances in induced versus spontaneous samples for 15 taxa when disease state was considered. This included potential pathogens like Haemophilus and Moraxella. Conclusion: When studying microbiota in sputum samples one should take into consideration how samples are collected and avoid the usage of both induced and spontaneous sputum in the same study

Comparing microbiota profiles in induced and spontaneous sputum samples in COPD patients

Background: Induced and spontaneous sputum are used to evaluate the airways microbiota. Whether the sputum types can be used interchangeably in microbiota research is unknown. Our aim was to compare microbiota in induced and spontaneous sputum from COPD patients sampled during the same consultation. Methods: COPD patients from Bergen, Norway, were followed between 2006/2010, examined during the stable state and exacerbations. 30 patients delivered 36 sample pairs. DNA was extracted by enzymatic and mechanical lysis methods. The V3-V4 region of the 16S rRNA gene was PCR-amplified and prepared for paired-end sequencing. Illumina Miseq System was used for sequencing, and Quantitative Insights Into Microbial Ecology (QIIME) and Stata were used for bioinformatics and statistical analyses. Results: Approximately 4 million sequences were sorted into 1004 different OTUs and further assigned to 106 different taxa. Pair-wise comparison of both taxonomic composition and beta-diversity revealed significant differences in one or both parameters in 1/3 of sample pairs. Alpha-diversity did not differ. Comparing abundances for each taxa identified, showed statistically significant differences between the mean abundances in induced versus spontaneous samples for 15 taxa when disease state was considered. This included potential pathogens like Haemophilus and Moraxella. Conclusion: When studying microbiota in sputum samples one should take into consideration how samples are collected and avoid the usage of both induced and spontaneous sputum in the same stud

COPD_BERGEN_Fastq175

Resulting Illumina fastq files from 175 sputum samples collected as part of the Bergen COPD Cohort Study (BCCS) and its adjunct Bergen COPD Exacerbation Study (BCES)