METHODS: We report the largest multicentre evaluation of the COPD airway mycobiome to date, including participants from Asia (Singapore and Malaysia) and the UK (Scotland) when stable (n=337) and during exacerbations (n=66) as well as nondiseased (healthy) controls (n=47). Longitudinal mycobiome analysis was performed during and following COPD exacerbations (n=34), and examined in terms of exacerbation frequency, 2-year mortality and occurrence of serum specific IgE (sIgE) against selected fungi.
RESULTS: A distinct mycobiome profile is observed in COPD compared with controls as evidenced by increased α-diversity (Shannon index; p<0.001). Significant airway mycobiome differences, including greater interfungal interaction (by co-occurrence), characterise very frequent COPD exacerbators (three or more exacerbations per year) (permutational multivariate ANOVA; adjusted p<0.001). Longitudinal analyses during exacerbations and following treatment with antibiotics and corticosteroids did not reveal any significant change in airway mycobiome profile. Unsupervised clustering resulted in two clinically distinct COPD groups: one with increased symptoms (COPD Assessment Test score) and Saccharomyces dominance, and another with very frequent exacerbations and higher mortality characterised by Aspergillus, Curvularia and Penicillium with a concomitant increase in serum sIgE levels against the same fungi. During acute exacerbations of COPD, lower fungal diversity associates with higher 2-year mortality.
CONCLUSION: The airway mycobiome in COPD is characterised by specific fungal genera associated with exacerbations and increased mortality.
RESEARCH QUESTION: What is the association between chitinase activity, airway fungi and clinical outcomes in bronchiectasis and bronchiectasis-COPD overlap?
STUDY DESIGN AND METHODS: A prospective cohort of 463 individuals were recruited across five hospital sites in three countries (Singapore, Malaysia, and Scotland) including individuals who were not diseased (n = 35) and who had severe asthma (n = 54), COPD (n = 90), bronchiectasis (n = 241) and BCO (n = 43). Systemic chitinase levels were assessed for bronchiectasis and BCO and related to clinical outcomes, airway Aspergillus status, and underlying pulmonary mycobiome profiles.
RESULTS: Systemic chitinase activity is elevated significantly in bronchiectasis and BCO and exceed the activity in other airway diseases. CHIT1 activity strongly predicts bronchiectasis exacerbations and is associated with the presence of at least one Aspergillus species in the airway and frequent exacerbations (≥3 exacerbations/y). Subgroup analysis reveals an association between CHIT1 activity and the "frequent exacerbator" phenotype in South-East Asian patients whose airway mycobiome profiles indicate the presence of novel fungal taxa that include Macroventuria, Curvularia and Sarocladium. These taxa, enriched in frequently exacerbating South-East Asian patients with high CHIT1 may have potential roles in bronchiectasis exacerbations.
INTERPRETATION: Systemic CHIT1 activity may represent a useful clinical tool for the identification of fungal-driven "frequent exacerbators" with bronchiectasis in South-East Asian populations.
METHODS: This study used data from 6524 participants of the 1970 British Birth Cohort Study, an ongoing population-based birth cohort of individuals born in England, Scotland and Wales. Participants' socioeconomic position was indicated by occupational social class at age 26 and 46 years (the first and latest adult waves, respectively). Self-rated oral health was measured at age 46 years. The association between social mobility and adult oral health was assessed using conventional regression models and diagonal reference models, adjusting for gender, ethnicity, country of residence and residence area.
RESULTS: Over a fifth of participants (22.2%) reported poor self-rated oral health at age 46 years. In conventional regression analysis, the odds ratios for social mobility varied depending on whether they were adjusted for social class of origin or destination. In addition, all social trajectories had greater odds of reporting poor oral health than non-mobile adults in class I/II. In diagonal reference models, both upward (Odds Ratio 0.79; 95% CI 0.63-0.99) and downward mobility (0.90; 95% CI 0.71-1.13) were inversely associated with poor self-rated oral health. The origin weight was 0.48 (95% CI 0.33-0.63), suggesting that social class of origin was as important as social class of destination.
CONCLUSION: This longitudinal analysis showed that intragenerational social mobility from young to middle adulthood was associated with self-rated oral health, independent of previous and current social class.
METHODS: We did a retrospective observational cohort study. We included consecutive people with ACS who were discharged from Scottish hospitals between January 2008 and December 2013 and who received DAPT after discharge followed by antiplatelet monotherapy. The rates of cardiovascular events were assessed during each 90-day period of DAPT treatment and 90-day period after stopping DAPT. Cardiovascular events were defined as a composite of death, ACS, transient ischaemic attack or stroke. Cox regression was used to identify predictors of cardiovascular events following DAPT cessation.
RESULTS: 1340 patients were included (62% male, mean age 64.9 (13.0) years). Cardiovascular events occurred in 15.7% (n=211) during the DAPT period (mean DAPT duration 175.1 (155.3) days) and in 16.7% (n=188) following DAPT cessation (mean of 2.7 years follow-up). Independent predictors for a cardiovascular event following DAPT cessation were age (HR 1.07; 95% CI 1.05 to 1.08; p<0.001), DAPT duration (HR 0.997; 95% CI 0.995 to 0.998; p<0.001) and having revascularisation therapy during the index admission (HR 0.58; 95% CI 0.39 to 0.85; p=0.005).
CONCLUSIONS: The rate of cardiovascular events was not significantly increased in the early period post-DAPT cessation compared with later periods in this ACS population. Increasing age, DAPT duration and lack of revascularisation therapy were associated with increased risk of cardiovascular events during long-term follow-up after DAPT cessation.
METHOD: Assessment of utilization (items dispensed) and expenditure of key LLAs (mainly statins) between 2001 and 2015 in Scotland alongside initiatives.
RESULTS: Multiple interventions over the years have increased international nonproprietary name prescribing (99% for statins) and preferential prescribing of generic versus patented statins, and reduced inappropriate prescribing of ezetimibe. This resulted in a 50% reduction in expenditure of LLAs between 2001 and 2015 despite a 412% increase in utilization, increased prescribing of higher dose statins (71% in 2015) especially atorvastatin following generic availability, and reduced prescribing of ezetimibe (reduced by 72% between 2010 and 2015). As a result, the quality of prescribing has improved.
CONCLUSION: Generic availability coupled with multiple measures has resulted in appreciable shifts in statin prescribing behavior and reduced ezetimibe prescribing, resulting in improvements in both the quality and efficiency of prescribing.