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Background Chronic airflow obstruction is a key characteristic of chronic obstructive pulmonary disease. We investigated whether isolated small airways obstruction is associated with chronic airflow obstruction later in life.Methods We used longitudinal data from 3957 participants of the multinational Burden of Obstructive Lung Disease study. We defined isolated small airways obstruction using the prebronchodilator mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FVC) (FEF25–75) if a result was less than the lower limit of normal (

Abstract Background The role of the pulmonary microbiome in sarcoidosis is unknown. The objectives of this study were the following: (1) examine whether the pulmonary fungal and bacterial microbiota differed in patients with sarcoidosis compared with controls; (2) examine whether there was an association between the microbiota and levels of the antimicrobial peptides (AMPs) in protected bronchoalveolar lavage (PBAL). Methods Thirty-five sarcoidosis patients and 35 healthy controls underwent bronchoscopy and were sampled with oral wash (OW), protected BAL (PBAL), and left protected sterile brushes (LPSB). The fungal ITS1 region and the V3V4 region of the bacterial 16S rRNA gene were sequenced. Bioinformatic analyses were performed with QIIME 2. The AMPs secretory leucocyte protease inhibitor (SLPI) and human beta defensins 1 and 2 (hBD-1 and hBD-2), were measured in PBAL by enzyme-linked immunosorbent assay (ELISA). Results Aspergillus dominated the PBAL samples in sarcoidosis. Differences in bacterial taxonomy were minor. There was no significant difference in fungal alpha diversity between sarcoidosis and controls, but the bacterial alpha diversity in sarcoidosis was significantly lower in OW (p = 0.047) and PBAL (p = 0.03) compared with controls. The beta diversity for sarcoidosis compared with controls differed for both fungi and bacteria. AMP levels were significantly lower in sarcoidosis compared to controls (SLPI and hBD-1: p < 0.01). No significant correlations were found between alpha diversity and AMPs. Conclusions The pulmonary fungal and bacterial microbiota in sarcoidosis differed from in controls. Lower antimicrobial peptides levels were seen in sarcoidosis, indicating an interaction between the microbiota and the innate immune system. Whether this dysbiosis represents a pathogenic mechanism in sarcoidosis needs to be confirmed in experimental studies. Video Abstract

Background and aim Several factors can influence measured lung function over time. The aim of this study was to investigate period and cohort effects on spirometric measures in a large general population sample in Norway during the 20th century, using Global Lung Function Initiative (GLI-2012) equations as a reference. Methods 36 466 subjects (born 1894–1969) from four cross-sectional surveys conducted between 1965 and 1999 were included, with harmonised data on smoking habits, respiratory symptoms, lung diseases, education and spirometry. Changes in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) z-scores in healthy subjects across surveys were explored to investigate period effects. Linear mixed-effects models of FEV1 and FVC z-scores on birth cohort, with survey as random effect, were used to investigate cohort effects, both in subjects of the total population and in healthy ones. Results Relatively higher FEV1 and FVC z-scores in healthy subjects were found in the first survey (1965–1970) compared to the more recent ones (1988–1999), suggesting period effects. FEV1 and FVC z-scores increased significantly with birth cohort from 1894 to 1935, after adjustment for covariates. A more stable trend of FEV1 and FVC z-scores with birth cohort was evidenced for subjects born more recently (1945–1969). Conclusions An increase of lung function with year of birth was observed in Norwegian subjects during the first half of the 20th century. The impact of period effects on lung function decreased from 1965 to 1999.

Abstract Objective Little is known concerning the stability of the lower airway microbiome. We have compared the microbiota identified by repeated bronchoscopy in healthy subjects and patients with ostructive lung diseaseases (OLD). Methods 21 healthy controls and 41 patients with OLD completed two bronchoscopies. In addition to negative controls (NCS) and oral wash (OW) samples, we gathered protected bronchoalveolar lavage in two fractions (PBAL1 and PBAL2) and protected specimen brushes (PSB). After DNA extraction, we amplified the V3V4 region of the 16S rRNA gene, and performed paired-end sequencing (Illumina MiSeq). Initial bioinformatic processing was carried out in the QIIME-2 pipeline, identifying amplicon sequence variants (ASVs) with the DADA2 algorithm. Potentially contaminating ASVs were identified and removed using the decontam package in R and the sequenced NCS. Results A final table of 551 ASVs consisted of 19 × 106 sequences. Alpha diversity was lower in the second exam for OW samples, and borderline lower for PBAL1, with larger differences in subjects not having received intercurrent antibiotics. Permutational tests of beta diversity indicated that within-individual changes were significantly lower than between-individual changes. A non-parametric trend test showed that differences in composition between the two exams (beta diversity) were largest in the PSBs, and that these differences followed a pattern of PSB > PBAL2 > PBAL1 > OW. Time between procedures was not associated with increased diversity. Conclusion The airways microbiota varied between examinations. However, there is compositional microbiota stability within a person, beyond that of chance, supporting the notion of a transient airways microbiota with a possibly more stable individual core microbiome.

Patients with chronic obstructive pulmonary disease (COPD) are prone to developing arterial hypertension, and many patients are treated with the calcium channel blocker amlodipine. However, it remains unclear whether using this drug potentially affects the risk of acute severe exacerbations (AECOPD) and all-cause mortality in these patients. The data were collected from Danish national registries, containing complete information on health, prescriptions, hospital admissions, and outpatient clinic visits. The COPD patients (n = 48,488) were matched via propensity score on known predictors of the primary outcome in an active comparator design. One group was exposed to amlodipine treatment, and the other was exposed to bendroflumethiazide, since both of these drugs are considered to be the first choice for the treatment of arterial hypertension according to Danish guidelines. The use of amlodipine was associated with a reduced risk of death from all causes at the 1-year follow-up (hazard ratio 0.69, 95% confidence interval: 0.62–0.76) compared with the use of bendroflumethiazide in the matched patients. No difference in the risk of severe AECOPD was found. In the COPD patients, amlodipine use was associated with a lower risk of death from all causes compared with the use of bendroflumethiazide. Amlodipine seems to be a safe first choice for the treatment of arterial hypertension in COPD patients.

Abstract Background Studies on the airway microbiome have been performed using a wide range of laboratory protocols for high-throughput sequencing of the bacterial 16S ribosomal RNA (16S rRNA) gene. We sought to determine the impact of number of polymerase chain reaction (PCR) steps (1- or 2- steps) and choice of target marker gene region (V3 V4 and V4) on the presentation of the upper and lower airway microbiome. Our analyses included lllumina MiSeq sequencing following three setups: Setup 1 (2-step PCR; V3 V4 region), Setup 2 (2-step PCR; V4 region), Setup 3 (1-step PCR; V4 region). Samples included oral wash, protected specimen brushes and protected bronchoalveolar lavage (healthy and obstructive lung disease), and negative controls. Results The number of sequences and amplicon sequence variants (ASV) decreased in order setup1 > setup2 > setup3. This trend appeared to be associated with an increased taxonomic resolution when sequencing the V3 V4 region (setup 1) and an increased number of small ASVs in setups 1 and 2. The latter was considered a result of contamination in the two-step PCR protocols as well as sequencing across multiple runs (setup 1). Although genera Streptococcus, Prevotella, Veillonella and Rothia dominated, differences in relative abundance were observed across all setups. Analyses of beta-diversity revealed that while oral wash samples (high biomass) clustered together regardless of number of PCR steps, samples from the lungs (low biomass) separated. The removal of contaminants identified using the Decontam package in R, did not resolve differences in results between sequencing setups. Conclusions Differences in number of PCR steps will have an impact of final bacterial community descriptions, and more so for samples of low bacterial load. Our findings could not be explained by differences in contamination levels alone, and more research is needed to understand how variations in PCR-setups and reagents may be contributing to the observed protocol bias.

BackgroundThe lower airways microbiome and host immune response in chronic pulmonary diseases are incompletely understood. We aimed to investigate possible microbiome characteristics and key antimicrobial peptides and proteins in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD).Methods12 IPF patients, 12 COPD patients and 12 healthy controls were sampled with oral wash (OW), protected bronchoalveolar lavage (PBAL) and right lung protected sterile brushings (rPSB). The antimicrobial peptides and proteins (AMPs), secretory leucocyte protease inhibitor (SLPI) and human beta defensins 1 and 2 (hBD-1 & hBD-2), were measured in PBAL by enzyme linked immunosorbent assay (ELISA). The V3V4 region of the bacterial 16S rDNA gene was sequenced. Bioinformatic analyses were performed with QIIME 2.ResultshBD-1 levels in PBAL for IPF were lower compared with COPD. The predominant phyla in IPF were Firmicutes, Bacteroides and Actinobacteria; Proteobacteria were among top three in COPD. Differential abundance analysis at genus level showed significant differences between study groups for less abundant, mostly oropharyngeal, microbes. Alpha diversity was lower in IPF in PBAL compared to COPD (p = 0.03) and controls (p = 0.01), as well as in rPSB compared to COPD (p = 0.02) and controls (p = 0.04). Phylogenetic beta diversity showed significantly more similarity for IPF compared with COPD and controls. There were no significant correlations between alpha diversity and AMPs.ConclusionsIPF differed in microbial diversity from COPD and controls, accompanied by differences in antimicrobial peptides. Beta diversity similarity between OW and PBAL in IPF may indicate that microaspiration contributes to changes in its microbiome.

Background Few studies have examined the stability of the pulmonary mycobiome. We report longitudinal changes in the oral and pulmonary mycobiome of participants with and without COPD in a large-scale bronchoscopy study (MicroCOPD). Methods Repeated sampling was performed in 30 participants with and 21 without COPD. We collected an oral wash (OW) and a bronchoalveolar lavage (BAL) sample from each participant at two time points. The internal transcribed spacer 1 region of the ribosomal RNA gene cluster was PCR amplified and sequenced on an Illumina HiSeq sequencer. Differences in taxonomy, alpha diversity, and beta diversity between the two time points were compared, and we examined the effect of intercurrent antibiotic use. Results Sample pairs were dominated by Candida. We observed less stability in the pulmonary taxonomy compared to the oral taxonomy, additionally emphasised by a higher Yue-Clayton measure in BAL compared to OW (0.69 vs 0.22). No apparent effect was visually seen on taxonomy from intercurrent antibiotic use or participant category. We found no systematic variation in alpha diversity by time either in BAL (p-value 0.16) or in OW (p-value 0.97), and no obvious clusters on bronchoscopy number in PCoA plots. Pairwise distance analyses showed that OW samples from repeated sampling appeared more stable compared to BAL samples using the Bray-Curtis distance metric (p-value 0.0012), but not for Jaccard. Conclusion Results from the current study propose that the pulmonary mycobiome is less stable than the oral mycobiome, and neither COPD diagnosis nor intercurrent antibiotic use seemed to influence the stability.

BackgroundCOPD and coronary heart disease (CHD) frequently co-occur, yet which COPD phenotypes are most prone to CHD is poorly understood. The aim of this study was to see whether COPD patients did have a true higher risk for CHD than subjects without COPD, and to examine a range of potential factors associated with CHD in COPD patients and controls.Methods347 COPD patients and 428 non-COPD controls, were invited for coronary computed tomography angiography (CCTA) and pulmonary CT. Arterial blood gas, bioelectrical impedance and lung function was measured, and a detailed medical history taken. The CCTA was evaluated for significant coronary stenosis and calcium score (CaSc), and emphysema defined as >10% of total area Results12.6% of the COPD patients and 5.7% of the controls had coronary stenosis (p100 compared to 31.6% of the controls (p100 was 1.68 (1.12-2.53) in COPD patients compared with controls. Examining the risk of significant stenosis and CaSc>100 among COPD patients, no variable was associated with significant stenosis, whereas male sex [OR 2.85 (1.56-5.21)], age [OR 3.74 (2.42-5.77)], statin use [OR 2.23 (1.23-4.50)] were associated with CaSc>100, after adjusting for body composition, pack-years, C-reactive protein, use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), diabetes, emphysema score, GOLD category, exacerbation frequency, eosinophilia, and hypoxemia.ConclusionCOPD patients were more likely to have CHD, but neither emphysema score, lung function, exacerbation frequency, nor hypoxemia predicted presence of either coronary stenosis or CaSc>100.

Abstract Background The low bacterial load in samples acquired from the lungs, have made studies on the airway microbiome vulnerable to contamination from bacterial DNA introduced during sampling and laboratory processing. We have examined the impact of laboratory contamination on samples collected from the lower airways by protected (through a sterile catheter) bronchoscopy and explored various in silico approaches to dealing with the contamination post-sequencing. Our analyses included quantitative PCR and targeted amplicon sequencing of the bacterial 16S rRNA gene. Results The mean bacterial load varied by sample type for the 23 study subjects (oral wash>1st fraction of protected bronchoalveolar lavage>protected specimen brush>2nd fraction of protected bronchoalveolar lavage; p

Abstract Background Evidence from several studies show poor guideline adherence to COPD treatment, but no such study has been undertaken in Norway. The objectives of this study, was to estimate and compare the guideline adherence to COPD treatment in general population-based and hospital-recruited COPD patients, and find possible predictors of guideline adherence. Methods From the prospective, observational EconCOPD-study, we analysed guideline adherence for 90 population-based COPD cases compared to 245 hospital-recruited COPD patients. Overall guideline adherence was defined as correct pharmacological treatment, and influenza vaccination the preceding year, and having received smoking cessation advice. Multivariate logistic regression analysis was performed with the dichotomous outcome overall guideline adherence adjusting for relevant variables. Results The overall guideline adherence for population-based COPD cases was 6.7%, significantly lower than the 29.8% overall guideline-adherence amongst hospital-recruited COPD patients. Adherence to pharmacological treatment guidelines was 10.0 and 35.5%, for the two recruitment sources, respectively. GOLD-stage 3 to 4 was associated with significantly better guideline adherence compared to GOLD-stage 2 (OR (95% CI) 18.9 (8.37,42.7)). The unadjusted difference between the two recruitment sources was completely explained by degree of airflow obstruction. Conclusion Overall guideline adherence was very low for both recruitment sources. We call for increased attention from authorities and healthcare personnel to improve the quality of care given to this patient group.

Background: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients. The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations. Objectives: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex. Methods: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey. Results: Among asthmatic subjects, higher percentage declines of FEV1 and FEV1/FVC were associated with higher FeNO levels (p = 0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p = 0.001) and females (p = 0.001) in stratified analyses.Percentage increase in FEV1 after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV1 and FeNO levels in non-smokers and women, regardless of asthma status. Conclusions: We found a relationship between elevated FeNO and larger FEV1 decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects.

BackgroundThe fungal part of the pulmonary microbiome (mycobiome) is understudied. We report the composition of the oral and pulmonary mycobiome in participants with COPD compared to controls in a large-scale single-centre bronchoscopy study (MicroCOPD).MethodsOral wash and bronchoalveolar lavage (BAL) was collected from 93 participants with COPD and 100 controls. Fungal DNA was extracted before sequencing of the internal transcribed spacer 1 (ITS1) region of the fungal ribosomal RNA gene cluster. Taxonomic barplots were generated, and we compared taxonomic composition, Shannon index, and beta diversity between study groups, and by use of inhaled steroids.ResultsThe oral and pulmonary mycobiomes from controls and participants with COPD were dominated by Candida, and there were more Candida in oral samples compared to BAL for both study groups. Malassezia and Sarocladium were also frequently found in pulmonary samples. No consistent differences were found between study groups in terms of differential abundance/distribution. Alpha and beta diversity did not differ between study groups in pulmonary samples, but beta diversity varied with sample type. The mycobiomes did not seem to be affected by use of inhaled steroids.ConclusionOral and pulmonary samples differed in taxonomic composition and diversity, possibly indicating the existence of a pulmonary mycobiome.

This study determined the association between respiratory symptoms and death from respiratory causes over a period of 45 years. In four cohorts of random samples of Norwegian populations with 103,881 participants, 43,731 persons had died per 31 December 2016. In total, 5,949 (14%) had died from respiratory diseases; 2,442 (41%) from lung cancer, 1,717 (29%) chronic obstructive pulmonary disease (COPD), 1,348 (23%) pneumonia, 119 (2%) asthma, 147 (2%) interstitial lung disease and 176 (3%) other pulmonary diseases. Compared with persons without respiratory symptoms the multivariable adjusted hazard ratio (HR) for lung cancer deaths increased with score of breathlessness on effort and cough and phlegm, being 2.6 (95% CI 2.1-3.2) for breathlessness score 3 and 2.1 (95% CI 1.7-2.5) for cough and phlegm score 5. The HR of COPD death was 6.4 (95% CI 5.4-7.7) for breathlessness score 3 and 3.0 (2.4-3.6) for cough and phlegm score 5. Attacks of breathlessness and wheeze score 2 had a HR of 1.6 (1.4-1.9) for COPD death. The risk of pneumonia deaths increased also with higher breathlessness on effort score, but not with higher cough and phlegm score, except for score 2 with HR 1.5 (1.2-1.8). In this study with >2.4 million person-years at risk, a positive association was observed between scores of respiratory symptoms and deaths due to COPD and lung cancer. Respiratory symptoms are thus important risk factors, which should be followed thoroughly by health care practitioners for the benefit of public health.

Background Data on discomfort and complications from research bronchoscopy in chronic obstructive pulmonary disease (COPD) and asthma is limited. We present complications and discomfort occurring within a week after bronchoscopy, and investigate personal and procedural risk factors.Methods 239 subjects with COPD, asthma or without lung disease underwent research bronchoscopies as part of a microbiome study of the lower airways (the MicroCOPD study). Bronchoscopy was done in the supine position with oral scope insertion with the option of light conscious alfentanil sedation. Sampling consisted of protected specimen brushes, bronchoalveolar lavage, small volume lavage and for some, endobronchial biopsies. Bleeding, desaturation, cough, haemodynamic changes, dyspnoea and other events that required an unplanned intervention or early termination of bronchoscopy were prospectively recorded. Follow-up consisted of a telephone interview where subjects rated discomfort and answered questions about fever sensation and respiratory symptoms in the week following bronchoscopy.Results An unplanned intervention or early termination of bronchoscopy was required in 25.9% of bronchoscopies. Three subjects (1.3%) experienced potentially severe complications, of which all recovered without sequelae. COPD subjects experienced more dyspnoea than controls. Sedation and lower age was associated with less unplanned intervention or premature termination. About half of the subjects (47.7%) reported fever. Discomfort was associated with postprocedural fever, dread of bronchoscopy, higher score on the COPD Assessment Test and never-smoking. In subjects undergoing more than one bronchoscopy, the first bronchoscopy was often predictive for complications and postprocedural fever in the repeated bronchoscopy.Conclusion Research bronchoscopies were not associated with more complications or discomfort in COPD subjects. 47.7% experienced postbronchoscopy fever sensation, which was associated with discomfort.

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS.

Aim The aim of this study was to investigate whether the compositionality of the lower airway microbiota predicts later exacerbation risk in persons with COPD in a cohort study. Materials and methods We collected lower airways microbiota samples by bronchoalveolar lavage and protected specimen brushes, and oral wash samples from 122 participants with COPD. Bacterial DNA was extracted from all samples, before we sequenced the V3-V4 region of the 16S RNA gene. The frequency of moderate and severe COPD exacerbations was surveyed in telephone interviews and in a follow-up visit. Compositional taxonomy and α and β diversity were compared between participants with and without later exacerbations. Results The four most abundant phyla were Firmicutes, Bacteroidetes, Proteobacteria and Fusobacteria in both groups, and the four most abundant genera were Streptococcus, Veillonella, Prevotella and Gemella. The relative abundances of different taxa showed a large variation between samples and individuals, and no statistically significant difference of either compositional taxonomy, or α or β diversity could be found between participants with and without COPD exacerbations within follow-up. Conclusion The findings from the current study indicate that individual differences in the lower airway microbiota in persons with COPD far outweigh group differences between frequent and nonfrequent COPD exacerbators, and that the compositionality of the microbiota is so complex as to present large challenges for use as a biomarker of later exacerbations.

Rationale There is limited knowledge on the effect of acute exacerbations in chronic obstructive pulmonary disease (AECOPD) on lung cancer risk in COPD patients with and without a history of asthma. This study aims to examine whether AECOPD is associated with risk of lung cancer, and whether the effect depends on a history of asthma. Methods In the GenKOLS study of 2003–2005, 852 subjects with COPD performed spirometry, and filled out questionnaires on smoking habits, symptoms and disease history. These data were linked to lung cancer data from the Cancer Registry of Norway through 2013. AECOPD, measured at baseline was the main predictor. To quantify differences in lung cancer risk, we performed Cox-proportional hazards regression. We adjusted for sex, age, smoking variables, body mass index, and lung function. Measurements and results During follow-up, 8.8% of the subjects with, and 5.9% of the subjects without exacerbations were diagnosed with lung cancer. Cox regression showed a significant increased risk of lung cancer with one or more exacerbations in COPD patients without a history of asthma, HRR = 2.77 (95% CI 1.39–5.52). We found a significant interaction between a history of asthma and AECOPD on lung cancer. Conclusions AECOPD is associated with an increased risk of lung cancer in COPD patients without a history of asthma.

Asthma often remains uncontrolled, despite the fact that the pharmacological treatment has undergone large changes. We studied changes in the treatment of asthma over a 20-year period and identified factors associated with the regular use of inhaled corticosteroid (ICS) treatment. Changes in the use of medication were determined in 4617 randomly selected subjects, while changes in adults with persistent asthma were analysed in 369 participants. The study compares data from three surveys in 24 centres in 11 countries. The use of ICSs increased from 1.7% to 5.9% in the general population and the regular use of ICSs increased from 19% to 34% among persistent asthmatic subjects. The proportion of asthmatic subjects reporting asthma attacks in the last 12 months decreased, while the proportion that had seen a doctor in the last 12 months remained unchanged (42%). Subjects with asthma who had experienced attacks or had seen a doctor were more likely to use ICSs on a regular basis. Although ICS use has increased, only one-third of subjects with persistent asthma take ICSs on a regular basis. Less than half had seen a doctor during the last year. This indicates that underuse of ICSs and lack of regular healthcare contacts remains a problem in the management of asthma.

BackgroundExacerbations of chronic obstructive pulmonary disease (COPD) are debilitating events and spur disease progression. Infectious causes are frequent; however, it is unknown to what extent exacerbations are caused by larger shifts in the airways' microbiota. The aim of the current study was to analyse the changes in microbial composition between stable state and during exacerbations, and the corresponding immune response.MethodsThe study sample included 36 COPD patients examined at stable state and exacerbation from the Bergen COPD Cohort and Exacerbations studies, and one patient who delivered sputum on 13 different occasions during the three-year study period. A physician examined the patients at all time points, and sputum induction was performed by stringent protocol. Only induced sputum samples were used in the current study, not spontaneously expectorated sputum. Sputum inflammatory markers (IL-6, IL-8, IL-18, IP-10, MIG, TNF-α) and antimicrobial peptides (AMPs, i.e. LL-37/hCAP-18, SLPI) were measured in supernatants, whereas target gene sequencing (16S rRNA) was performed on corresponding cell pellets. The microbiome bioinformatics platform QIIME2TM and the statistics environment R were applied for bioinformatics analyses.ResultsLevels of IP-10, MIG, TNF-α and AMPs were significantly different between the two disease states. Of 36 sample pairs, 24 had significant differences in the 12 most abundant genera between disease states. The diversity was significantly different in several individuals, but not when data was analysed on a group level. The one patient case study showed longitudinal dynamics in microbiota unrelated to disease state.ConclusionChanges in the sputum microbiota with changing COPD disease states are common, and are accompanied by changes in inflammatory markers. However, the changes are highly individual and heterogeneous events.

Abstract Objectives This study aims to evaluate the diagnostic accuracy and reliability of a new, brief questionnaire, ‘Brief Assessment of Impaired Cognition– Questionnaire’ (BASIC-Q) for detection of cognitive impairment, primarily developed for use in primary care. BASIC-Q has three components: Self-report, Informant report, and Orientation. Self-report and Orientation are completed by the individual and Informant report is answered by a close relative. Methods We included 275 participants ≥ 70 years, without a prior diagnosis of dementia, and with a close relative who agreed to participate as an informant. Participants were included prospectively in 14 general practices in urban and rural Denmark using a convenience sampling method. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the informant-completed Functional Activities Questionnaire (FAQ) and reported memory concern were used as a reference standard for the classification of the participants’ cognitive function. Results BASIC-Q demonstrated a fair to good diagnostic accuracy to differentiate between people with cognitive impairment and normal cognition with an area under the ROC curve (AUC) of 0.84 (95% CI 0.79–0.89) and a sensitivity and specificity of 0.80 (95% CI 0.72–0.87) and 0.71 (95% CI 0.63–0.78). A prorated BASIC-Q score derived from BASIC-Q without Informant report had significantly lower classification accuracy than the full BASIC-Q. The test-retest reliability of BASIC-Q was good with an intraclass correlation coefficient of 0.84. Conclusion BASIC-Q is a brief, easy-to-use questionnaire for identification of cognitive impairment in older adults. It demonstrated fair to good classification accuracy in a general practice setting and can be a useful case-finding tool when suspecting dementia in primary health care.

BackgroundThe Cross-Cultural Neuropsychological Test Battery (CNTB) is a novel test battery specifically designed to reduce the impact of multiculturality in cognitive assessment.ObjectiveWe aimed to validate the CNTB in Spaniards in patients with Alzheimer's disease (AD), including patients at mild cognitive impairment (MCI) and mild dementia stages, and Parkinson's disease with MCI (PD-MCI).MethodsThirty patients with AD-MCI, 30 with AD-dementia (AD-D), and 30 with PD-MCI were recruited. Each clinical group was compared against a healthy control group (HC) with no differences in sex, age, or years of education. Intergroup comparisons, ROC analysis, and cut-off scores were calculated.ResultsAD-MCI scored lower than HC in those subtests associated with episodic memory and verbal fluency. AD-D also showed lower scores in executive functions and visuospatial tests. Effect sizes for all the subtests were large. PD-MCI showed lower performance than HC in memory and executive functions, particularly on error scores, with large effect sizes. Comparing AD-MCI and PD-MCI, AD-MCI had lower memory scores, while PD-MCI showed the worst performance in executive functions. CNTB showed appropriate convergent validity with standardized neuropsychological tests measuring the same cognitive domains. We obtained similar cut-off scores to previous studies performed in other populations.ConclusionsThe CNTB showed appropriate diagnostic properties in AD and PD, including those stages with mild cognitive impairment. This supports the utility of the CNTB for the early detection of cognitive impairment in AD and PD.

Background: Filipino normative data for neuropsychological tests are lacking. Objectives: This study aimed to determine the Filipino normative data for the Filipino Norming Project (FNP) Neuropsychological Battery, combining the Alzheimer’s Disease Assessment Scale – Cognitive (ADAS-Cog) and the Neuropsychological Test Battery from the Uniform Dataset of Alzheimer’s Disease Center (UDS-ADC). Methods: We recruited participants 60 years and older with normal cognition (MMSE score of 25 and above and did not fulfill criteria for dementia according to DSM-IV criteria). Psychologists administered the tests to the study participants. We conducted multivariate analyses to study the effect of age, gender, and education on test performance. Results: A total of 191 participants underwent the FNP Neuropsychological Test Battery. The mean age was 68.8 years (SD 5.4). The majority were female (84.1%). The mean score of ADAS-Cog was 9.98 (SD 4.74). The effect of education was prominent throughout the cognitive domains tested while the effect of age was limited to a few cognitive domains. The mean ADAS-Cog scores were 11.80 ± 4.40 for primary education, 9.93 ± 5.08 for secondary, and 8.15 ± 3.95 for tertiary. On average, women scored 2.75 points lower than men and performed better on the verbal components. Men performed better on the constructional praxis component. The same effect of education and gender was observed for the UDS-ADC. Conclusion: For the first time, normative data are available for the ADAS-Cog and UDS-ADC for a Filipino older population. This study stresses the importance of establishing population-specific normative data, taking into account the specific sociocultural and linguistic context of that population.

Abstract Background Along with the ageing of the general population, Europe’s migrant populations are also ageing, thus posing new challenges for dementia care services, particularly if the services are to be adjusted to persons with different linguistic and cultural backgrounds. From the perspective of health professionals, this study aims to explore challenges involved in identifying, assessing and diagnosing people with cognitive impairment/dementia who have different linguistic and cultural backgrounds. Methods Research on health professionals experiences regarding the management of dementia among immigrants is scarce and qualitative methods was used to address the objective of the study. Using qualitative in-depth interviews and focus-group discussions, we sought to gather participants’ experiences regarding the diagnostic process for immigrants with dementia. The material was analysed and interpreted based on Kvale and Brinkmann’s descriptions of three different contexts of interpretation: self-understanding, critical common-sense understanding, and theoretical understanding. Results Health professionals described how families could attribute symptoms of dementia to processes of normal ageing, while others saw the symptoms as something shameful; both instances delayed or hindered help-seeking. Many clinicians had limited experience with older immigrants suffering from dementia, and general practitioners (GPs) in particular experienced difficulties assessing dementia due to language barriers and difficulties related to the involvement of the family or an interpreter. The findings illustrate challenges in assessment, such as unfamiliarity with test situations among those being assessed and lack of knowledge regarding appropriate diagnostic tools among health professionals. Lack of continuity and poor information exchange in the chain of care seem to reinforce many of these challenges. Conclusions Detection, treatment and care may be improved if primary care professionals strengthen their cross-cultural competences. Training in communication skills and in the use of cross-cultural assessment tools may help build competence and confidence when assessing and caring for people with different cultural and linguistic backgrounds. Closer collaboration among families, nurses in home-based services, dementia teams, and GPs may facilitate close monitoring of a patient over time. Such collaboration requires sufficient information exchange during transitions in the chain of care, continuity among health professionals, and a shared understanding of the goals for treatment and care.

Background: Establishing a diagnosis of dementia in young patients may be complex and have significant implications for the patient. The aim of this study was to evaluate the quality of the diagnostic work-up in young patients diagnosed with dementia in the clinical routine. Methods: Two hundred patients were randomly selected from 891 patients aged ≤65 years registered with a diagnosis of dementia for the first time in 2008 in Danish hospitals, and 159 medical records were available for review. Three raters evaluated their medical records for the completeness of the diagnostic work-up on which the diagnosis of dementia had been based, using evidence-based guidelines for the diagnostic evaluation of dementia as reference standards. Results: According to the rater review, only 111 (70%) patients met the clinical criteria for dementia. An acceptable diagnostic work-up including all items of recommended basic diagnostic evaluation was performed in only 24%, although more often (28%) in the subgroup of patients where dementia was confirmed by raters. Conclusion: This first nationwide study of unselected young patients registered with a diagnosis of dementia indicated that the concept of dementia may be misinterpreted by clinicians and that a diagnosis of dementia in the young is only rarely based on a complete basic diagnostic work-up, calling for increased competency.

ABSTRACT Objective Evaluate the accuracy of two semantic categories of the verbal fluency test (supermarket and animal categories) to separate healthy elderly individuals and lower educated Alzheimer’s disease patients. Methods We evaluated 69 older adults with less than 5 years of schooling, consisting of 31 healthy elderly, and 38 patients diagnosed with Alzheimer’s disease. Semantic verbal fluency was evaluated using the animal and supermarket categories. Mann-Whitney U and Independent t Tests were used to compare the two groups, and the diagnostic accuracy of the tests was analyzed by sensitivity, specificity, likelihood ratio’s, and the Area Under the Curve (AUC). Results We found a significant difference between the healthy older and Alzheimer’s disease groups, in both, animal (p = 0.014) and supermarket verbal fluency (p < 0.001). The supermarket category showed better overall diagnostic accuracy (AUC = 0.840, 95% CI = 0.746-0.933; p < 0.001) compared to the animal category (AUC = 0.671, 95% CI = 0.543-0.800; p = 0.014). Conclusion The supermarket category of semantic verbal fluency provides better accuracy than the animal category for the identification of dementia in a Brazilian elderly population with low educational level.