A mixed methods analysis of existing assessment and evaluation tools (AETs) for mental health applications.

Introduction: Mental health Applications (MH Apps) can potentially improve access to high-quality mental health care. However, the recent rapid expansion of MH Apps has created growing concern regarding their safety and effectiveness, leading to the development of AETs (Assessment and Evaluation Tools) to help guide users. This article provides a critical, mixed methods analysis of existing AETs for MH Apps by reviewing the criteria used to evaluate MH Apps and assessing their effectiveness as evaluation tools. Methods: To identify relevant AETs, gray and scholarly literature were located through stakeholder consultation, Internet searching via Google and a literature search of bibliographic databases Medline, APA PsycInfo, and LISTA. Materials in English that provided a tool or method to evaluate MH Apps and were published from January 1, 2000, to January 26, 2021 were considered for inclusion. Results: Thirteen relevant AETs targeted for MH Apps met the inclusion criteria. The qualitative analysis of AETs and their evaluation criteria revealed that despite purporting to focus on MH Apps, the included AETs did not contain criteria that made them more specific to MH Apps than general health applications. There appeared to be very little agreed-upon terminology in this field, and the focus of selection criteria in AETs is often IT-related, with a lesser focus on clinical issues, equity, and scientific evidence. The quality of AETs was quantitatively assessed using the AGREE II, a standardized tool for evaluating assessment guidelines. Three out of 13 AETs were deemed 'recommended' using the AGREE II. Discussion: There is a need for further improvements to existing AETs. To realize the full potential of MH Apps and reduce stakeholders' concerns, AETs must be developed within the current laws and governmental health policies, be specific to mental health, be feasible to implement and be supported by rigorous research methodology, medical education, and public awareness.

Stakeholders' views and opinions on existing guidelines on "How to Choose Mental Health Apps".

Background: Mental health Applications (Mhealth Apps) can change how healthcare is delivered. However, very little is known about the efficacy of Mhealth Apps. Currently, only minimum guidance is available in Assessment and Evaluation Tools (AETs). Therefore, this project aims to understand AET developers' perspectives and end users' experiences and opinions on "how to choose a Mhealth App". Objective: The primary objectives were: (1) obtaining stakeholder's opinions and experiences of development and use of AETs for Mhealth Apps, their weaknesses and strengths, and barriers in their implementation of Mhealth Apps; (2) the experiences of App users, their analyzation and, obstacles in the use of apps; and (3) to quantify themes related to choosing a Mhealth App. Methods: This qualitative study, used a sampling method to recruit six stakeholders (one App developer, two AET developers, an individual with lived experience of mental health illness, and two physicians) who were interviewed using a topic guide. These were examined by researchers (CT, WK, & FN) using thematic content analysis. Additionally, an anonymous online survey of 107 individuals was conducted. Findings: Our analyses revealed six main themes: (a) needs and opportunities; (b) views on Mhealth apps; (c) views & opinions on AETs; (d) implementation barriers; (e) system of evaluation and; (f) future directions. The first key concept was, all stakeholders agreed that Apps could significantly impact mental health and that end-users were unaware of mental health AETs and Apps. Secondly, due to commercial interests, end-users reliability of App evaluations requires clear conflict-free guidelines. Thirdly, AETs should be evaluated and developed through a rigorous methodology. Finally, stakeholders shared insights into future developments for AETs and Mhealth Apps. Additionally, online survey respondents chose a "health professional" as their preferred source of guidance in selecting a Mhealth app (84%) and best suited to develop guidelines (70%). Conclusion: The interviews and survey highlight the need for Mhealth Apps to be regulated and the importance of health professionals' engagement in the implementation process. Similarly, without well-defined roles for App evaluations within the health care system, it is unlikely that AETs will have wider spread use and impact without risk.

Neighbourhood-level social capital, marginalisation, and the incidence of schizophrenia and schizoaffective disorder in Toronto, Canada: a retrospective population-based cohort study.

BACKGROUND: Studies have shown mixed results regarding social capital and the risk of developing a psychotic disorder, and this has yet to be studied in North America. We sought to examine the relationship between neighbourhood-level marginalisation, social capital, and the incidence of schizophrenia and schizoaffective disorder in Toronto, Canada. METHODS: We used a retrospective population-based cohort to identify incident cases of schizophrenia and schizoaffective disorder over a 10 year period and accounted for neighbourhood-level marginalisation and a proxy indicator of neighbourhood social capital. Mixed Poisson regression models were used to estimate adjusted incidence rate ratios (aIRRs). RESULTS: In the cohort (n = 649 020) we identified 4841 incident cases of schizophrenia and schizoaffective disorder. A 27% variation in incidence was observed between neighbourhoods. All marginalisation dimensions, other than ethnic concentration, were associated with incidence. Compared to areas with low social capital, areas with intermediate social capital in the second [aIRR = 1.17, 95% confidence interval (CI) 1.03-1.33] and third (aIRR = 1.23, 95% CI 1.08-1.40) quintiles had elevated incidence rates after accounting for marginalisation. There was a higher risk associated with the intermediate levels of social capital (aIRR = 1.18, 95% CI 1.00-1.39) when analysed in only the females in the cohort, but the CI includes the possibility of a null effect. CONCLUSIONS: The risk of developing schizophrenia and schizoaffective disorder in Toronto varies by neighbourhood and is associated with socioenvironmental exposures. Social capital was not linearly associated with risk, and risk differs by sex and social capital quintile. Future research should examine these relationships with different forms of social capital and examine how known individual-level risk factors impact these findings.

Pulmonary Embolism during a Retrial of Low-dose Clozapine.

Pulmonary emboli (PE) are increasingly recognized as an adverse effect of clozapine. However, little is known about the characteristics or mechanisms of clozapine-associated PE. We present a case of a 34-year-old with treatment-refractory schizophrenia who developed rhabdomyolysis during his first clozapine trial. During re-trial on a lower dose than his initial trial, the patient developed chest pain that he attributed to "pacemakers." The pleuritic description and associated tachycardia prompted medical workup and the patient was ultimately diagnosed with a clozapine-associated PE. The patient's only risk factors for PE were obesity and tobacco use, while his hypercoagulability workup was unrevealing. Clozapine use was continued at a lower dose following these adverse effects given inefficacy of other agents in managing the patient's psychotic symptoms. The patient experienced significant relief of psychotic symptoms with continued clozapine therapy and a course of electroconvulsive therapy. The patient's presentation was unusual in that it occurred during a retrial of clozapine, after the initial trial was stopped when he developed rhabdomyolysis. This case demonstrates the importance of maintaining vigilance for PE in patients on clozapine as well as not dismissing somatic complaints in patients experiencing psychosis. Additionally, given his history rhabdomyolysis, an uncommon adverse effect of clozapine, the development of a second uncommon adverse effect (PE) raises the question of whether these events may be associated.

The Incidence of Psychotic Disorders and Area-level Marginalization in Ontario, Canada: A Population-based Retrospective Cohort Study.

BACKGROUND: There is limited Canadian evidence on the impact of socio-environmental factors on psychosis risk. We sought to examine the relationship between area-level indicators of marginalization and the incidence of psychotic disorders in Ontario. METHODS: We conducted a retrospective cohort study of all people aged 14 to 40 years living in Ontario in 1999 using health administrative data and identified incident cases of psychotic disorders over a 10-year follow-up period. Age-standardized incidence rates were estimated for census metropolitan areas (CMAs). Poisson regression models adjusting for age and sex were used to calculate incidence rate ratios (IRRs) based on CMA and area-level marginalization indices. RESULTS: There is variation in the incidence of psychotic disorders across the CMAs. Our findings suggest a higher rate of psychotic disorders in areas with the highest levels of residential instability (IRR = 1.26, 95% confidence interval [CI], 1.18 to 1.35), material deprivation (IRR = 1.30, 95% CI, 1.16 to 1.45), ethnic concentration (IRR = 1.61, 95% CI, 1.38 to 1.89), and dependency (IRR = 1.35, 95% CI, 1.18 to 1.54) when compared to areas with the lowest levels of marginalization. Marginalization attenuates the risk in some CMAs. CONCLUSIONS: There is geographic variation in the incidence of psychotic disorders across the province of Ontario. Areas with greater levels of marginalization have a higher incidence of psychotic disorders, and marginalization attenuates the differences in risk across geographic location. With further study, replication, and the use of the most up-to-date data, a case may be made to consider social policy interventions as preventative measures and to direct services to areas with the highest risk. Future research should examine how marginalization may interact with other social factors including ethnicity and immigration.

Protocol for a multi-phase, mixed methods study to develop and evaluate culturally adapted CBT to improve community mental health services for Canadians of south Asian origin.

BACKGROUND: Canadians of South Asian (SA) origin comprise the largest racialized group in Canada, representing 25.6% of what Statistics Canada terms "visible minority populations". South Asian Canadians are disproportionately impacted by the social determinants of health, and this can result in high rates of mood and anxiety disorders. These factors can negatively impact mental health and decrease access to care, thereby increasing mental health inequities. Cognitive Behavioural Therapy (CBT) in its current form is not suitable for persons from the non-western cultural backgrounds. Culturally adapted Cognitive Behavioural Therapy (CaCBT) is an evidence-based practice. CaCBT is more effective than standard CBT and can reduce dropouts from therapy compared with standard CBT. Thus, CaCBT can increase access to mental health services and improve outcomes for immigrant, refugee and ethno-cultural and racialized populations. Adapting CBT for growing SA populations in Canada will ensure equitable access to effective and culturally appropriate interventions. METHODS: The primary aim of the study is to develop and evaluate CaCBT for Canadian South Asian persons with depression and anxiety and to gather data from stakeholders to develop guidelines to culturally adapt CBT. This mixed methods study will use three phases: (1) cultural adaptation of CBT, (2) pilot feasibility of CaCBT and (3) implementation and evaluation of CaCBT. Phase 1 will use purposive sampling to recruit individuals from four different groups: (1) SA patients with depression and anxiety, (b) caregivers and family members of individuals affected by anxiety and depression, (c) mental health professionals and (d) SA community opinion leaders. Semi-structured interviews will be conducted virtually and analysis of interviews will be informed by an ethnographic approach. Phase 2 will pilot test the newly developed CaCBT for feasibility, acceptability and effectiveness via quantitative methodology and a randomized controlled trial, including an economic analysis. Phase 3 will recruit therapists to train and evaluate them in the new CaCBT. DISCUSSION: The outcome of this trial will benefit health services in Canada, in terms of helping to reduce the burden of depression and anxiety and provide better care for South Asians. We expect the results to help guide the development of better services and tailor existing services to the needs of other vulnerable groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT04010890. Registered on July 8, 2019.

Carriage of upper respiratory tract pathogens in rural communities of Sarawak, Malaysian Borneo.

INTRODUCTION: Pneumonia is a leading cause of death in Malaysia. Whilst many studies have reported the aetiology of pneumonia in Western countries, the epidemiology of pneumonia in Malaysia remains poorly understood. As carriage is a prerequisite for disease, we sought to improve our understanding of the carriage and antimicrobial resistance (AMR) of respiratory tract pathogens in Malaysia. The rural communities of Sarawak are an understudied part of the Malaysian population and were the focus of this study, allowing us to gain a better understanding of bacterial epidemiology in this population. METHODS: A population-based survey of bacterial carriage was undertaken in participants of all ages from rural communities in Sarawak, Malaysia. Nasopharyngeal, nasal, mouth and oropharyngeal swabs were taken. Bacteria were isolated from each swab and identified by culture-based methods and antimicrobial susceptibility testing conducted by disk diffusion or E test. RESULTS: 140 participants were recruited from five rural communities. Klebsiella pneumoniae was most commonly isolated from participants (30.0%), followed by Staphylococcus aureus (20.7%), Streptococcus pneumoniae (10.7%), Haemophilus influenzae (9.3%), Moraxella catarrhalis (6.4%), Pseudomonas aeruginosa (6.4%) and Neisseria meningitidis (5.0%). Of the 21 S. pneumoniae isolated, 33.3 and 14.3% were serotypes included in the 13 valent PCV (PCV13) and 10 valent PCV (PCV10) respectively. 33.8% of all species were resistant to at least one antibiotic, however all bacterial species except S. pneumoniae were susceptible to at least one type of antibiotic. CONCLUSION: To our knowledge, this is the first bacterial carriage study undertaken in East Malaysia. We provide valuable and timely data regarding the epidemiology and AMR of respiratory pathogens commonly associated with pneumonia. Further surveillance in Malaysia is necessary to monitor changes in the carriage prevalence of upper respiratory tract pathogens and the emergence of AMR, particularly as PCV is added to the National Immunisation Programme (NIP).

Ethnicity, Immigration Status, And Driving Under The Influence Of Alcohol.

BACKGROUND: Understanding risk factors for driving under the influence of alcohol (DUIA) informs development of effective interventions. This study examined the association between ethnicity, immigration status, and DUIA, exploring psychological distress and hazardous drinking as additional contributors. METHOD: Data were derived from the 2003-2011 cycles of the Centre for Addiction and Mental Health (CAMH) Monitor of 16,101 adults from Ontario, Canada. Hierarchical binary logistic regression analysis assessed self-identified ethnicity and immigration status as predictors of DUIA, adjusting for sociodemographics and driving exposure (Model 1), psychological distress (Model 2), and hazardous drinking (Model 3). RESULTS: In Model 1, respondents born outside of Canada had reduced odds of engaging in DUIA compared to those born in Canada (AOR = 0.72, 95%CI = 0.56 - 0.92). Relative to those identifying as Canadian, the odds of DUIA were significantly reduced for those identifying as East Asian (AOR = 0.28, 95%CI = 0.13 - 0.61) and South Asian (AOR = 0.52, 95%CI = 0.27 - 0.98). In Model 3, individuals who reported psychological distress (AOR = 1.69, 95%CI = 1.33 - 2.16) and those who reported hazardous drinking (AOR = 6.28, 95%CI= 5.13 - 7.69) were more likely to DUIA. Those identifying as East Asian continued to have reduced odds of DUIA compared to those identifying as Canadian (AOR = 0.38, 95%CI = 0.17 - 0.85). CONCLUSION: Individuals born outside of Canada were less likely to engage in DUIA than individuals born in Canada. Drivers who self-identified as East Asian were less likely to DUIA than those who self-identified as Canadian. Understanding ethnic differences underlying divergent risks for DUIA will improve prevention initiatives and remedial measures programming.

The Promise of Psychosocial Therapies for Use with Immigrant, Refugee, Ethno-Cultural and Racialized Populations.

Psychotherapies are a fundamental part of mental healthcare. These have been shown to be effective treatments for a wide range of mental disorders, from anxiety and depression to psychoses such as schizophrenia. However, there is evidence that the effectiveness of psychotherapies may vary, and these may need to be adapted to work optimally for different cultural groups. In addition, some diagnoses that are more common in refugee populations may require specific interventions. This paper examines the effectiveness of psychotherapeutic techniques for immigrant, refugee, ethno-cultural and racialized populations.

Drivers of year-to-year variation in exacerbation frequency of COPD: analysis of the AERIS cohort.

The association between exacerbation aetiology and exacerbation frequency is poorly understood. We analysed 2-year follow-up data from a prospective observational study of patients with chronic obstructive pulmonary disease (COPD) (www.clinicaltrials.gov identifier number NCT01360398) to evaluate year-to-year variation in exacerbation frequency and related aetiology. A total of 127 patients underwent blood and sputum sampling monthly and at exacerbation to detect respiratory infections and eosinophilic inflammation; 103 continued into year 2 and 88 completed both years. The most common bacterial species at stable state and exacerbation was Haemophilus influenzae. Among infrequent exacerbators (one exacerbation per year), the incidence of viral infection at exacerbation was high (60.0% (95% CI 35.1-81.7%) in year 1 and 78.6% (53.4-94.2%) in year 2). Those with more frequent exacerbations tended to have higher relative incidence of bacterial than viral infection. Patients with at least two additional exacerbations in year 2 versus year 1 had a higher risk of H. influenzae colonisation at stable state than those with at least two fewer exacerbations, as detected by culture (OR 1.43 (95% CI 0.71-2.91) versus 0.63 (0.40-1.01), p=0.06) and PCR (1.76 (95% CI 0.88-3.51) versus 0.56 (0.37-0.86), p<0.01). This was not seen with other infection types or eosinophilic inflammation. Analysis of the same cohort over 2 years showed, for the first time, that changes in yearly COPD exacerbation rate may be associated with variations in H. influenzae colonisation.

Unmet Health Care Needs for Syrian Refugees in Canada: A Follow-up Study.

Unmet health care needs are under explored among refugees. Previously we found unmet health care needs in Syrian refugees may be higher than in the general Canadian population (Oda et al. CMAJ Open 5(2):E354-E358, 2017; Oda et al. J Immigr Minor Health, 2018. https://doi.org/10.1007/s10903-018-0780-z). This follow-up study with Syrian refugees who entered Canada between July 2015 and July 2016 aimed to understand if there are changes in unmet health care needs 6 months to a year after baseline collection. The number reporting unmet needs was high (42.6%). Although some refugees had their needs met, unmet health needs persist, and it seems that they are linked with sponsorship pathway and post-migration socio-economic position. While caution should be used generalizing these results, they do suggest that greater coordination between services may be needed as many of the refugees report unmet needs within months of arriving and continue to report needs after being here for a period up to 2 years.

Differences in Self-Reported Health and Unmet Health Needs Between Government Assisted and Privately Sponsored Syrian Refugees: A Cross-Sectional Survey.

Between November 2015 and January 2017, the Government of Canada resettled over 40,000 Syrian refugees through different sponsorship programs (GAR and PSR). Timely access to healthcare is essential for good health and successful integration. However, refugee support differs depending on sponsorship program, which may lead to differences in healthcare service access and needs. A cross-sectional study with a sample of Syrian refugees was conducted to assess healthcare access, and perceived physical and mental health status. Results indicate demographic and healthcare access differences between GARs and PSRs. GARs reported significantly lower perceived physical and mental health, as well as, higher unmet healthcare needs than PSRs. GARs are among the most vulnerable refugees; they report higher needs, more complex medical conditions and tend to have more difficulty re-settling. These factors likely combine to help explain lower self-reported health and higher health needs in our sample compared to PSRs.

A high-throughput system used to determine frequency and distribution of phosphine resistance across large geographical regions.

BACKGROUND: Next-generation sequencing can enable genetic surveys of large numbers of individuals. We developed a genotyping-by-sequencing assay for detecting strong phosphine resistance alleles in the dihydrolipoamide dehydrogenase (dld) gene of Rhyzopertha dominica populations. The assay can estimate the distribution and frequency of resistance variants in thousands of individual insects in a single run. RESULTS: We analysed 1435 individual insects collected over a 1-year period from 59 grain-storage sites including farms (n = 29) and central storages (n = 30) across eastern Australia. Resistance alleles were detected in 49% of samples, 38% of farms and 60% of central storages. Although multiple alleles were detected, only two resistance variants (P49S and K142E) were widespread and each appeared to have a distinct but overlapping geographical distribution. CONCLUSION: The type of structure in which the grain is stored had a strong effect on resistance allele frequency. We observed higher frequencies of resistance alleles in bunker storages at central sites compared with other storage types. This contributed to the higher frequencies of resistance alleles in bulk-handling facilities relative to farms. The discovery of a storage structure that predisposes insects to resistance highlights the utility of our high-throughput assay system for improvement of phosphine resistance management practices. © 2018 Society of Chemical Industry.

Impact of radiologically stratified exacerbations: insights into pneumonia aetiology in COPD.

BACKGROUND: COPD patients have increased risk of developing pneumonia, which is associated with poor outcomes. It can be symptomatically indistinguishable from exacerbations, making diagnosis challenging. Studies of pneumonia in COPD have focused on hospitalised patients and are not representative of the ambulant COPD population. Therefore, we sought to determine the incidence and aetiology of acute exacerbation events with evidence of pneumonic radiographic infiltrates in an outpatient COPD cohort. METHODS: One hundred twenty-seven patients with moderate to very severe COPD aged 42-85 years underwent blood and sputum sampling over one year, at monthly stable visits and within 72 h of exacerbation symptom onset. 343 exacerbations with chest radiographs were included. RESULTS: 20.1% of exacerbations had pneumonic infiltrates. Presence of infiltrate was highly seasonal (Winter vs summer OR 3.056, p = 0.027). In paired analyses these exacerbation events had greater increases in systemic inflammation. Bacterial detection rate was higher in the pneumonic group, with Haemophilus influenzae the most common bacteria in both radiological groups. Viral detection and sputum microbiota did not differ with chest radiograph appearance. CONCLUSIONS: In an outpatient COPD cohort, pneumonic infiltrates at exacerbation were common, and associated with more intense inflammation. Bacterial pathogen detection and lung microbiota were not distinct, suggesting that exacerbations and pneumonia in COPD share common infectious triggers and represent a continuum of severity rather than distinct aetiological events. TRIAL REGISTRATION: Trial registration Number: NCT01360398 .

Ecology and diversity in upper respiratory tract microbial population structures from a cross-sectional community swabbing study.

PURPOSE: Respiratory tract infections (RTIs) are responsible for over 2.8 million deaths per year worldwide with pathobiont carriage a required precursor to infection. We sought to determine carriage epidemiology for both bacterial and viral respiratory pathogens as part of a large population-based cross-sectional carriage study. METHODOLOGY: Nose self-swab samples were collected in two separate time-points, May to August 2012 (late spring/summer) and February to April 2013 (winter/early spring). The presence of six bacterial species: S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus, P. aeruginosa and N. meningitidis in addition to respiratory syncytial virus, influenza viruses A and B, rhinovirus/enterovirus, coronavirus, parainfluenza viruses 1-3 and adenovirus was determined using culture and PCR methods.Results/Key findings. Carriage was shown to vary with age, recent RTI and the presence of other species. Spatial structures of microbial communities were more disordered in the 0-4 age group and those with recent RTI. Species frequency distributions were flatter than random expectation in young individuals (X2=20.42, P=0.002), indicating spatial clumping of species consistent with facilitative relationships. Deviations from a neutral model of ecological niches were observed in summer samples and from older individuals but not in the winter or younger individuals (0-4 years), suggesting the presence of seasonal and age-dependent niche processes in respiratory community assembly. CONCLUSION: The application of epidemiological methods and ecological theory to respiratory tract samples has yielded novel insights into the factors that drive microbial community composition.

Variant Linkage Analysis Using de Novo Transcriptome Sequencing Identifies a Conserved Phosphine Resistance Gene in Insects.

Next-generation sequencing methods enable identification of the genetic basis of traits in species that have no prior genomic information available. The combination of next-generation sequencing, variant analysis, and linkage is a powerful way of identifying candidate genes for a trait of interest. Here, we used a comparative transcriptomics [RNA sequencing (RNAseq)] and genetic linkage analysis approach to identify the rph1 gene. rph1 variants are responsible for resistance to the fumigant phosphine (PH3) that is used to control insect pests of stored grain. In each of the four major species of pest insect of grain we have investigated, there are two major resistance genes, rph1 and rph2, which interact synergistically to produce strongly phosphine-resistant insects. Using RNAseq and genetic linkage analyses, we identified candidate resistance (rph1) genes in phosphine-resistant strains of three species: Rhyzopertha dominica (129 candidates), Sitophilus oryzae (206 candidates), and Cryptolestes ferrugineus (645 candidates). We then compared these candidate genes to 17 candidate resistance genes previously mapped in Tribolium castaneum and found only one orthologous gene, a cytochrome b5 fatty acid desaturase (Cyt-b5-r), to be associated with the rph1 locus in all four species. This gene had either missense amino acid substitutions and/or insertion/deletions/frameshift variants in each of 18 phosphine-resistant strains that were not observed in the susceptible strains of the four species. We propose a model of phosphine action and resistance in which phosphine induces lipid peroxidation through reactive oxygen species generated by dihydrolipoamide dehydrogenase, whereas disruption of Cyt-b5-r in resistant insects decreases the polyunsaturated fatty acid content of membranes, thereby limiting the potential for lipid peroxidation.

Relationship of CT-quantified emphysema, small airways disease and bronchial wall dimensions with physiological, inflammatory and infective measures in COPD.

BACKGROUND: COPD is a complex, heterogeneous disease characterised by progressive development of airflow limitation. Spirometry provides little information about key aspects of pathology and is poorly related to clinical outcome, so other tools are required to investigate the disease. We sought to explore the relationships between quantitative CT analysis with functional, inflammatory and infective assessments of disease to identify the utility of imaging to stratify disease to better predict outcomes and disease response. METHODS: Patients from the AERIS study with moderate-very severe COPD underwent HRCT, with image analysis determining the quantity of emphysema (%LAA<- 950), small airways disease (E/I MLD) and bronchial wall thickening (Pi10). At enrolment subjects underwent lung function testing, six-minute walk testing (6MWT), blood sampling for inflammatory markers and sputum sampling for white cell differential and microbiological culture and PCR. RESULTS: 122 subjects were included in this analysis. Emphysema and small airways disease had independent associations with airflow obstruction (ß = - 0.34, p < 0.001 and ß = - 0.56, p < 0.001). %LAA<- 950 had independent associations with gas transfer (ß = - 0.37, p < 0.001) and E/I MLD with RV/TLC (ß = 0.30, p =0.003). The distance walked during the 6MWT was not associated with CT parameters, but exertional desaturation was independently associated with emphysema (ß = 0.73, p < 0.001). Pi10 did not show any independent associations with lung function or functional parameters. No CT parameters had any associations with sputum inflammatory cells. Greater emphysema was associated with lower levels of systemic inflammation (CRP ß = - 0.34, p < 0.001 and fibrinogen ß = - 0.28, p =0.003). There was no significant difference in any of the CT parameters between subjects where potentially pathogenic bacteria were detected in sputum and those where it was not. CONCLUSIONS: This study provides further validation for the use of quantitative CT measures of emphysema and small airways disease in COPD as they showed strong associations with pulmonary physiology and functional status. In contrast to this quantitative CT measures showed few convincing associations with biological measures of disease, suggesting it is not an effective tool at measuring disease activity.

Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations.

BACKGROUND: Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD. OBJECTIVE: To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes. METHODS: We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene. We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes. RESULTS: The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies. Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated. We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis. CONCLUSIONS: Subtypes of COPD have distinct bacterial compositions and stabilities over time. Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future. This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient. TRIAL REGISTRATION NUMBER: Results, NCT01360398.