A comparison of GOLD 2019 and 2023 recommendations to contemporaneous real-world inhaler treatment patterns for chronic obstructive pulmonary disease management in Singapore.

Background: In 2019 and 2023, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) provided updated strategies for modifying the therapy of patients with chronic obstructive pulmonary disease (COPD) and high exacerbation risk. A key update since the 2019 guidelines recommends considering blood eosinophil count to guide decisions on inhaled corticosteroid (ICS) treatment. To evaluate the potential impact of these updated recommendations, this study aimed to assess how extensively future practice would diverge from contemporaneous prescribing practices at a single center in Singapore, assuming adherence to the 2019 and 2023 GOLD guidelines. Methods: Retrospective cohort analysis of the Changi General Hospital COPD data warehouse involving patients aged ≥40 years hospitalized for a COPD exacerbation (October 2018-April 2020) receiving long-acting muscarinic antagonist (LAMA), LAMA plus a long-acting beta2-agonist (LABA), or an ICS plus LABA at admission. The proportion of patients eligible for treatment escalations per GOLD 2019 and 2023 recommendations was calculated. Results: In total, 268 patients were included (mean age 73 years; 91% male). At admission, 19%, 59%, and 22% of patients were receiving LAMA, LAMA + LABA, and ICS + LABA, respectively. Overall, 226 patients would have been eligible for treatment escalation per GOLD 2019 or 2023 recommendations; 31 (13.7%) had treatment escalations consistent with GOLD 2019 guidelines and 34 (15%) received treatment escalations consistent with GOLD 2023 guidelines. A total of 205 patients (76.5%) remained on the same treatment regimen at hospital discharge as they were receiving at admission. Lower measured post-bronchodilator forced expiratory volume in 1 second was associated with treatment escalations that would have been GOLD-concordant (P=0.028), as was increased number of emergency department/hospital visits in the last year (P=0.048). Conclusions: Compared with real-world clinical practice, a significantly higher proportion of patients may be eligible for treatment escalation under the GOLD 2019 and 2023 eosinophil-directed algorithms.

Year-to-year trajectories of hospital utilisation rates among patients with COPD: a real-world, single-centre, retrospective cohort study.

OBJECTIVES: The long-term clinical trajectory of chronic obstructive pulmonary disease (COPD) in terms of year-to-year hospital utilisation rates can be highly variable and is not well studied. We investigated year-to-year trends of hospitalisation or emergency department (ED) visits among patients with COPD over 3 years, identified distinct trajectories and examined associated predictive factors. DESIGN: A retrospective cohort study. SETTING: Data were extracted from the Changi General Hospital, Singapore COPD data warehouse. PARTICIPANTS: Patients with COPD aged ≥40 years with 3 years of follow-up data. PRIMARY AND SECONDARY OUTCOME MEASURES: The yearly rates of hospitalisations or ED visits, stratified by COPD-related or all-cause, were described. Group-based trajectory modelling was used to identify clinically distinct trajectories year-by-year. Baseline predictive factors associated with different trajectories were examined. RESULTS: In total, 396 patients were analysed (median age 70 years; 87% male). Four trajectories were generated for year-to-year trends in COPD-related hospitalisations/ED visits (C1-C4: consistently frequent, consistently infrequent, improving and worsening); post-bronchodilator forced expiratory volume in 1 second (FEV1) was a significant predictor of trajectory, with worse lung function being the main factor associated with less favourable trajectories. For all-cause hospitalisations/ED visits, four trajectories were identified (A1-A4: infrequent and stable, frequent and stable, frequent and decreasing, frequent and increasing); significant differences in age (p=0.041), sex (p=0.016) and ethnicity (p=0.005) were found between trajectories. Higher overall comorbidity burden was a key determinant in less favourable trajectories of all-cause hospitalisations/ED visits. CONCLUSIONS: Distinct trajectories were demonstrated for hospitalisations/ED visits related to COPD or all causes, with predictive associations between FEV1 and COPD trajectory and between comorbidities and all-cause trajectory. Trajectories carry nuanced prognostic information and may be useful for clinical risk stratification to identify high-risk individuals for preventative treatments.

Findings from a decade of experience following implementation of a Rapid Response System into an Asian hospital.

Aim: Rapid response systems (RRS) are present in many acute hospitals in western nations but are not widely adopted in Asia. The influence of healthcare culture and the effect of implementing an RRS over time are infrequently reported. We describe the introduction a RRS into a Singaporean hospital and the barriers encountered. The efferent limb activation rates, cardiac arrest rates and unplanned intensive care unit (ICU) admissions are trended over eleven years. Methods: We conducted a retrospective observational study using prospectively collected data derived from administrative and Medical Emergency Team (MET) databases. Results: The RRS used a MET with a single parameter track and trigger and physician led efferent limb. Barriers encountered included clinical leadership buy-in, assembling and equipping the efferent team, maintaining a non-punitive mindset, improving accessibility to MET and communicating the impact of the MET. Over an 11-year period with 488,252 hospital admissions, MET activation rates increased from 1.6/1000 admissions (2009) to 14.1/1000 admissions (2019). Code blue activations and unplanned ICU admission rates decreased from 2.9 to 1.7 and from 8.8 to 2.0/1000 admissions, respectively over the 11 years. There were associations between increasing MET activation rate and reduction in code blue activations (p = 0.013) and unplanned medical ICU admission rates (p = 0.001). Conclusion: Implementing, sustaining and continued improvement of an RRS in Singapore is possible despite challenges encountered. With increasing activation rates over a decade, there were reductions in cardiac arrest rates and unplanned medical ICU admissions.

Association between proximity to COVID-19 and the quality of life of healthcare workers.

BACKGROUND: The coronavirus disease 2019 (COVID-19) affects almost all countries in the world and it impacts every aspect of people's life-physically, mentally, and socio-economically. There are several research studies examining the impact of this pandemic on health, however, very few studies examining the impact of this pandemic on quality of life. This study aimed to investigate the association between proximity to the COVID-19 and quality of life of healthcare workers and identify factors influencing quality of life. METHODS: A cross-sectional study was conducted among hospital staff in a tertiary hospital in Singapore. Data on demographic, medical history, lifestyle factors, psychosocial factors, and quality of life were collected using online self-administered questionnaire. Quality of life (QoL) was measured by the WHOQOL-BREF questionnaire. Robust linear regression was used to determine factors associated with quality of life. RESULTS: A total of 1911 participants were included in the analysis. The average age of participants was 38.25 (SD = 11.28) years old. 26.90% of participants had been quarantined, hospitalised, being suspected or diagnosed of having COVID-19 infection and they were found to have the lowest levels of QoL across all four domains (physical, psychological, social, and environmental domains). Participants who were singles or nurses, worked in shifts or worked longer hours, had chronic diseases were likely to have lower QoL scores compared to participants in other categories. Healthy lifestyle, social connectivity, resilience, social and workplace support were associated with higher QoL scores. CONCLUSIONS: In planning of measures which aim to improve QoL of healthcare workers, priority should be given to individuals who have been quarantined, hospitalised, being suspected, or diagnosed of having COVID-19 infection. In addition to the proximity of the COVID, lifestyle and psychosocial factors contribute to QoL of healthcare workers. Hence, multifaceted interventions are needed to improve QoL of healthcare workers.

Sensitisation to recombinant Aspergillus fumigatus allergens and clinical outcomes in COPD.

BACKGROUND: Variable clinical outcomes are reported with fungal sensitisation in chronic obstructive pulmonary disease (COPD), and it remains unclear which fungi and what allergens associate with the poorest outcomes. The use of recombinant as opposed to crude allergens for such assessment is unknown. METHODS: A prospective multicentre assessment of stable COPD (n=614) was undertaken in five hospitals across three countries: Singapore, Malaysia and Hong Kong. Clinical and serological assessment was performed against a panel of 35 fungal allergens including crude and recombinant Aspergillus and non-Aspergillus allergens. Unsupervised clustering and topological data analysis (TDA) approaches were employed using the measured sensitisation responses to elucidate if sensitisation subgroups exist and their related clinical outcomes. RESULTS: Aspergillus fumigatus sensitisation was associated with increased exacerbations in COPD. Unsupervised cluster analyses revealed two "fungal sensitisation" groups. The first was characterised by Aspergillus sensitisation and increased exacerbations, poorer lung function and worse prognosis. Polysensitisation in this group conferred even poorer outcome. The second group, characterised by Cladosporium sensitisation, was more symptomatic. Significant numbers of individuals demonstrated sensitisation responses to only recombinant (as opposed to crude) A. fumigatus allergens f 1, 3, 5 and 6, and exhibited increased exacerbations, poorer lung function and an overall worse prognosis. TDA validated these findings and additionally identified a subgroup within Aspergillus-sensitised COPD of patients with frequent exacerbations. CONCLUSION: Aspergillus sensitisation is a treatable trait in COPD. Measuring sensitisation responses to recombinant Aspergillus allergens identifies an important patient subgroup with poor COPD outcomes that remains overlooked by assessment of only crude Aspergillus allergens.

Characteristics of Patients with Chronic Obstructive Pulmonary Disease Treated with Long-Acting Bronchodilators in a Real-World Setting in Singapore: A Single-Center Observational Study.

Introduction: There is limited real-world evidence regarding clinical practice for chronic obstructive pulmonary disease (COPD) in Singapore. We compared baseline clinical characteristics and evaluated outcomes in patients with COPD who initiated treatment with either a long-acting muscarinic antagonist (LAMA) or a LAMA and a long-acting ß2-agonist (LAMA+LABA). Methods: This was a single-center observational study at Changi General Hospital, Singapore. Routine clinical data (hospital visits, case management, lung function, laboratory/imaging results, medication orders) were collected and compiled into a data warehouse. Eligible patients with COPD were ≥40 years old and newly prescribed LAMA or LAMA+LABA during the enrollment period. Patient characteristics in the baseline period (6 months) were compared between treatments. Clinical worsening was measured as a composite endpoint, defined as the first of a change in maintenance treatment class or a moderate-to-severe exacerbation during follow-up (12 months). Results: In total, 261 patients were included in the baseline period (LAMA: 73; LAMA+LABA: 188). In the baseline period, patients receiving LAMA+LABA versus LAMA had significantly lower body mass index, higher COPD Assessment Test score and worse lung function, and numerically higher exacerbation history. Prevalence of comorbidities was similar between treatment groups. In follow-up, high rates of clinical worsening were observed regardless of treatment regimen (LAMA: 38/73 [52%]; LAMA+LABA: 86/188 [46%]). Median time-to-clinical worsening was 340 days for the LAMA cohort and the raw median 154 days (interquartile range: 44-225) for the LAMA+LABA cohort. Median medication dispensation rate (0.86; interquartile range: 0.56-1.00) was similar between treatments. Conclusion: Patients initiating treatment with LAMA+LABA had more severe COPD than patients prescribed LAMA. The proportion of patients experiencing clinical worsening was similarly high in both cohorts, suggesting that early identification and treatment optimization are necessary.

Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer.

BACKGROUND: Tissue biopsy is an integral part of the diagnostic approach to lung cancer. It is however invasive and limited by heterogeneity. Liquid biopsies may complement tissue testing by providing additional molecular information and may be particularly helpful in patients from whom obtaining sufficient tissue for genomic profiling is challenging. METHODS: Patients with suspected lung cancer (n = 71) were prospectively recruited. Blood and diagnostic tissue samples were collected within 48 h of each other. Plasma cell-free DNA (cfDNA) testing was done using an ultrasensitive amplicon-based next-generation sequencing (NGS) panel (plasma NGS testing). For cases diagnosed as non-small cell lung carcinoma (NSCLC) via histology or cytology, targeted testing for epidermal growth factor receptor (EGFR) mutations was performed using tissue biopsy samples (tissue EGFR testing), where available. Concordance of clinically actionable mutations between methods and sample types was assessed. RESULTS: For confirmed NSCLC cases (n = 54), tissue EGFR test results were available only for 70.3% (38/54) due to sample inadequacies, compared to blood samples for 98.1% (53/54) cases. Tissue EGFR testing identified sensitizing EGFR (L858R or exon 19 deletion) mutation in 31.6% (12/38) of cases. Plasma NGS identified clinically actionable mutations in 37.7% (20/53) of cases, including EGFR mutations in two cases with no tissue EGFR results, and mutations in KRAS, BRAF, and MET. The overall sensitivity of sensitizing EGFR mutation detection by plasma NGS was 75% (9/12), and specificity was 100% (25/25) in patients tested in both tissue EGFR and plasma NGS (n = 37). In this cohort of patients, tissue EGFR testing alone informed clinical decisions in 22.2% (12/54) of cases. Adding plasma NGS to tissue EGFR testing increased the detection rate of actionable mutations to 42.6% (23/54), representing a 1.9-fold increase in clinically relevant findings. The average turnaround time of plasma NGS was shorter than standard tissue testing (10 vs. 29.9 days, p < 0.05). CONCLUSIONS: In the first-line setting, plasma NGS was highly concordant with tissue EGFR testing. Plasma NGS increases the detection of actionable findings with a shorter time to results. This study outlines the clinical utility of complementary plasma mutation profiling in the routine management of lung cancer patients.

High Frequency of Allergic Bronchopulmonary Aspergillosis in Bronchiectasis-COPD Overlap.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is associated with frequent exacerbations and poor outcomes in chronic respiratory disease, but remains underdiagnosed. The role of fungal sensitization in bronchiectasis-COPD overlap (BCO) is unknown. RESEARCH QUESTION: What is the occurrence and clinical relevance of Aspergillus sensitization and ABPA in BCO when compared with individuals with COPD or bronchiectasis without overlap? STUDY DESIGN: Prospective, observational, cross-sectional study. METHODS: We prospectively recruited 280 patients during periods of clinical stability with bronchiectasis (n = 183), COPD (n = 50), and BCO (n = 47) from six hospitals across three countries (Singapore, Malaysia, and Scotland). We assessed sensitization responses (as specific IgE) to a panel of recombinant Aspergillus fumigatus allergens and the occurrence of ABPA in relationship to clinical outcomes. RESULTS: Individuals with BCO show an increased frequency and clinical severity of ABPA compared with those with COPD and bronchiectasis without overlap. BCO-associated ABPA is associated with more severe disease, higher exacerbation rates, and lower lung function when compared with ABPA occurring in the absence of overlap. BCO with a severe bronchiectasis severity index (BSI; > 9) is associated significantly with the occurrence of ABPA that is unrelated to underlying COPD severity. CONCLUSIONS: BCO demonstrates a high frequency of ABPA that is associated with a severe BSI (> 9) and poor clinical outcomes. Clinicians should maintain a high index of suspicion for the potential development of ABPA in patients with BCO with high BSI.

Integrative microbiomics in bronchiectasis exacerbations.

Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion ( https://integrative-microbiomics.ntu.edu.sg ). Patients at greatest risk of exacerbation have less complex microbial co-occurrence networks, reduced diversity and a higher degree of antagonistic interactions in their airway microbiome. Furthermore, longitudinal interactome dynamics reveals microbial antagonism during exacerbation, which resolves following treatment in an otherwise stable multi-biome. Assessment of the Pseudomonas interactome shows that interaction networks, rather than abundance alone, are associated with exacerbation risk, and that incorporation of microbial interaction data improves clinical prediction models. Shotgun metagenomic sequencing of an independent cohort validated the multi-biome interactions detected in targeted analysis and confirmed the association with exacerbation. Integrative microbiomics captures microbial interactions to determine exacerbation risk, which cannot be appreciated by the study of a single microbial group. Antibiotic strategies probably target the interaction networks rather than individual microbes, providing a fresh approach to the understanding of respiratory infection.

Impact of structured curriculum with simulation on bronchoscopy.

BACKGROUND AND OBJECTIVE: Simulation enhances a physician's competency in procedural skills by accelerating ascent of the learning curve. Training programmes are moving away from the Halstedian model of 'see one, do one, teach one', also referred as medical apprenticeship. We aimed to determine if a 3-month structured bronchoscopy curriculum that incorporated simulator training could improve bronchoscopy competency among pulmonary medicine trainees. METHODS: We prospectively recruited trainees from hospitals with accredited pulmonary medicine programmes. Trainees from hospitals (A, B and C) were assigned to control group (CG) where they received training by traditional apprenticeship while trainees from hospital D were assigned to intervention group (IG) where they underwent 3-month structured curriculum that incorporated training with the bronchoscopy simulator. Two patient bronchoscopy procedures per trainee were recorded on video and scored independently by two expert bronchoscopists using the modified Bronchoscopy Skills and Tasks Assessment Tool (BSTAT) forms. A 25 multiple choice questions (MCQ) test was administered to all participants at the end of 3 months. RESULTS: Eighteen trainees participated; 10 in CG and eight in IG with equal female:male ratio. Competency assessed by modified BSTAT and MCQ tests was variable and not driven by volume as IG performed fewer patient bronchoscopies but demonstrated better BSTAT, airway anaesthesia and MCQ scores. Bronchoscopy simulator training was the only factor that correlated with better BSTAT (r = 0.80), MCQ (r = 0.85) and airway anaesthesia scores (r = 0.83), and accelerated the learning curve of IG trainees. CONCLUSION: An intensive 3-month structured bronchoscopy curriculum that incorporated simulator training led to improved cognitive and technical skill performance as compared with apprenticeship training.

Changes in Control Status of COPD Over Time and Their Consequences: A Prospective International Study / Cambios en el estado de control de la EPOC a lo largo del tiempo y sus consecuencias: un estudio internacional prospectivo

INTRODUCTION: Control status may be a useful tool to assess response to treatment at each clinical visit in COPD. Control status has demonstrated to have long-term predictive value for exacerbations, but there is no information about the short-term predictive value of the lack of control and changes in control status over time. METHOD: Prospective, international, multicenter study aimed at describing the short-term (6 months) prognostic value of control status in patients with COPD. Patients with COPD were classified as controlled/uncontrolled at baseline and at 3,6-month follow-up visits using previously validated criteria of control. Moderate and severe exacerbation rates were compared between controlled and uncontrolled visits and between patients persistently controlled, uncontrolled and those changing control status over follow-up. RESULTS: A total of 267 patients were analyzed: 80 (29.8%) were persistently controlled, 43 (16%) persistently uncontrolled and 144 (53.7%) changed control status during follow-up. Persistently controlled patients were more frequently men, with lower (not increased) body mass index and higher FEV1(%). During the 6 months following an uncontrolled patient visit the odds ratio (OR) for presenting a moderate exacerbation was 3.41 (95% confidence interval (CI) 2.47-4.69) and OR = 4.25 (95%CI 2.48-7.27) for hospitalization compared with a controlled patient visit. CONCLUSIONS: Evaluation of control status at each clinical visit provides relevant prognostic information about the risk of exacerbation in the next 6 months. Lack of control is a warning signal that should prompt investigation and action in order to achieve control status

INTRODUCCIÓN: El estado de control de la enfermedad puede ser una herramienta útil para evaluar la respuesta al tratamiento de la EPOC en cada asistencia a consulta. El estado de control de la enfermedad ha demostrado tener valor predictivo a largo plazo para las exacerbaciones, pero no existe información sobre el valor predictivo a corto plazo de la falta de control de la EPOC y los cambios en dicho control a lo largo del tiempo. MÉTODO: Estudio prospectivo, internacional, multicéntrico enfocado en describir el valor pronóstico a corto plazo (6 meses) del estado de control de la enfermedad en pacientes con EPOC. Los pacientes con EPOC se clasificaron como con enfermedad controlada/sin controlar al inicio del estudio y en las 3 visitas de seguimiento separadas 6 meses, utilizando criterios de control previamente validados. Se compararon las tasas de exacerbación moderada y grave entre visitas en las que la enfermedad estaba controlada y aquellas en las que no y entre pacientes con control persistente de la enfermedad, pacientes sin control de la enfermedad y aquellos cuyo estado de control cambió durante el seguimiento. RESULTADOS: Se analizó a un total de 267 pacientes: 80 (29,8%) presentaron control persistente de la enfermedad, 43 (16%) permanecieron con enfermedad no controlada de manera persistente y 144 (53,7%) presentaron un cambio en el estado de control de su EPOC durante el seguimiento. Los pacientes con control persistente de su enfermedad fueron con mayor frecuencia hombres, con un índice de masa corporal más bajo (no elevado) y un FEV1 (%) más alto. Durante los 6 meses posteriores a una visita en la que la enfermedad del paciente no estaba controlada, la odds ratio (OR) para presentar una exacerbación moderada fue de 3,41 (intervalo de confianza [IC] del 95%: 2,47 a 4,69) y la OR = 4,25 (IC del 95%: 2,48 a 7,27) para la hospitalización, en comparación con una visita en la que la EPOC estaba controlada. CONCLUSIONES: La evaluación del estado de control de la EPOC en cada asistencia a consulta proporciona información pronóstica relevante sobre el riesgo de exacerbación en los próximos 6 meses. La falta de control es una señal de alarma que debe motivar la investigación y la acción para lograr el control de la enfermedad

The development and psychometric evaluation of the Clinicians' Attitudes towards Responding and Escalating care of Deteriorating patients scale.

BACKGROUND: Validated measures of ward nurses' safety cultures in relation to escalations of care in deteriorating patients are lacking. OBJECTIVES: This study aimed to develop and evaluate the psychometric properties of the Clinicians' Attitudes towards Responding and Escalating care of Deteriorating patients (CARED) scale for use among ward nurses. METHODS: The study was conducted in two phases: scale development and psychometric evaluation. The scale items were developed based on a systematic literature review, informant interviews, and expert reviews (n = 15). The reliability and validity of the scale were examined by administering the scale to 617 registered nurses with retest evaluations (n = 60). The factor structure of the CARED scale was examined in a split-half analysis with exploratory and confirmatory factor analyses. The internal consistency, test-retest reliability, convergent validity, and known-group validity of the scale were also analysed. RESULTS: A high overall content validity index of 0.95 was obtained from the validations of 15 international experts from seven countries. A three-factor solution was identified from the final 22 items: 'beliefs about rapid response system', 'fears about escalating care', and 'perceived confidence in responding to deteriorating patients'. The internal consistency reliability of the scale was supported with a good Cronbach's alpha value of 0.86 and a Spearman-Brown split-half coefficient of 0.87. An excellent test-retest reliability was demonstrated, with an intraclass correlation coefficient of 0.92. The convergent validity of the scale was supported with an existing validated scale. The CARED scale also demonstrated abilities to discriminate differences among the sample characteristics. CONCLUSIONS: The final 22-item CARED scale was tested to be a reliable and valid scale in the Singaporean setting. The scale may be used in other settings to review hospitals' rapid response systems and to identify strategies to support ward nurses in the process of escalating care in deteriorating ward patients.

A high-risk airway mycobiome is associated with frequent exacerbation and mortality in COPD.

INTRODUCTION: The chronic obstructive pulmonary disease (COPD) bacteriome associates with disease severity, exacerbations and mortality. While COPD patients are susceptible to fungal sensitisation, the role of the fungal mycobiome remains uncertain. 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.

Changes in Control Status of COPD Over Time and Their Consequences: A Prospective International Study.

INTRODUCTION: Control status may be a useful tool to assess response to treatment at each clinical visit in COPD. Control status has demonstrated to have long-term predictive value for exacerbations, but there is no information about the short-term predictive value of the lack of control and changes in control status over time. METHOD: Prospective, international, multicenter study aimed at describing the short-term (6 months) prognostic value of control status in patients with COPD. Patients with COPD were classified as controlled/uncontrolled at baseline and at 3,6-month follow-up visits using previously validated criteria of control. Moderate and severe exacerbation rates were compared between controlled and uncontrolled visits and between patients persistently controlled, uncontrolled and those changing control status over follow-up. RESULTS: A total of 267 patients were analyzed: 80 (29.8%) were persistently controlled, 43 (16%) persistently uncontrolled and 144 (53.7%) changed control status during follow-up. Persistently controlled patients were more frequently men, with lower (not increased) body mass index and higher FEV1(%). During the 6 months following an uncontrolled patient visit the odds ratio (OR) for presenting a moderate exacerbation was 3.41 (95% confidence interval (CI) 2.47-4.69) and OR=4.25 (95%CI 2.48-7.27) for hospitalization compared with a controlled patient visit. CONCLUSIONS: Evaluation of control status at each clinical visit provides relevant prognostic information about the risk of exacerbation in the next 6 months. Lack of control is a warning signal that should prompt investigation and action in order to achieve control status.

Method of respiratory rate measurement using a unique wearable platform and an adaptive optical-based approach.

BACKGROUND: An efficient and accurate method of respiratory rate measurement is still missing in hospital general wards and triage. The goal of this study is to propose a method of respiratory rate measurement that has a potential to be used in general wards, triage, and different hospital settings with comparable performance. We propose a method of respiratory rate measurement that combines a unique wearable platform with an adaptive and optical approach. The optical approach is based on a direct-contact optical diffuse reflectance phenomenon. An adaptive algorithm is developed that computes the first respiratory rate and uses it to select a band. The band then chooses a set of unique optimized parameters in the algorithm to calculate and improve the respiratory rate. We developed a study to compare the proposed method against reference manual counts from 82 patients diagnosed with respiratory diseases. RESULTS: We found good agreement between the proposed method of respiratory rate measurement and reference manual counts. The performance of the proposed method highlighted deviations with a 95% confidence interval (C.I.) of - 3.34 and 3.67 breaths per minute (bpm) and a mean bias and standard deviation (STD) of 0.05 bpm and 2.56 bpm, respectively. CONCLUSIONS: The performance of the proposed method of respiratory rate measurement is comparable with current manual counting and other respiratory rate devices reported. The method has additional advantages that include ease-of-use, quick setup time, and being mobile for wider clinical use. The proposed method has the potential as a tool to measure respiratory rates in a number of use cases.

Environmental fungal sensitisation associates with poorer clinical outcomes in COPD.

INTRODUCTION: Allergic sensitisation to fungi such as Aspergillus are associated to poor clinical outcomes in asthma, bronchiectasis and cystic fibrosis; however, clinical relevance in COPD remains unclear. METHODS: Patients with stable COPD (n=446) and nondiseased controls (n=51) were prospectively recruited across three countries (Singapore, Malaysia and Hong Kong) and screened against a comprehensive allergen panel including house dust mites, pollens, cockroach and fungi. For the first time, using a metagenomics approach, we assessed outdoor and indoor environmental allergen exposure in COPD. We identified key fungi in outdoor air and developed specific-IgE assays against the top culturable fungi, linking sensitisation responses to COPD outcomes. Indoor air and surface allergens were prospectively evaluated by metagenomics in the homes of 11 COPD patients and linked to clinical outcome. RESULTS: High frequencies of sensitisation to a broad range of allergens occur in COPD. Fungal sensitisation associates with frequent exacerbations, and unsupervised clustering reveals a "highly sensitised fungal predominant" subgroup demonstrating significant symptomatology, frequent exacerbations and poor lung function. Outdoor and indoor environments serve as important reservoirs of fungal allergen exposure in COPD and promote a sensitisation response to outdoor air fungi. Indoor (home) environments with high fungal allergens associate with greater COPD symptoms and poorer lung function, illustrating the importance of environmental exposures on clinical outcomes in COPD. CONCLUSION: Fungal sensitisation is prevalent in COPD and associates with frequent exacerbations representing a potential treatable trait. Outdoor and indoor (home) environments represent a key source of fungal allergen exposure, amenable to intervention, in "sensitised" COPD.

Predictive value of control of COPD for risk of exacerbations: An international, prospective study.

BACKGROUND AND OBJECTIVE: The concept of clinical control in COPD has been developed to help in treatment decisions, but it requires validation in prospective studies. METHODS: This international, multicentre, prospective study aimed to validate the concept of control in COPD. Patients with COPD were classified as controlled/uncontrolled by clinical criteria or CAT scores at baseline and followed up for 18 months. The main outcome was the difference in rate of a composite endpoint of moderate and severe exacerbations or death over the 18-month follow-up period. RESULTS: A total of 307 patients were analysed (mean age = 68.6 years and mean FEV1 % = 52.5%). Up to 65% and 37.9% of patients were classified as controlled by clinical criteria or CAT, respectively. Controlled patients had significantly less exacerbations during follow-up (by clinical criteria: 1.1 vs 2.6, P < 0.001; by CAT: 1.1 vs 1.9, P = 0.014). Time to first exacerbation was significantly prolonged for patients controlled by clinical criteria only (median: 93 days, IQR: 63; 242 vs 274 days, IQR: 221; 497 days; P < 0.001). Control status by clinical criteria was a better predictor of exacerbations compared to CAT criteria (AUC: 0.67 vs 0.57). CONCLUSION: Control status, defined by easy-to-obtain clinical criteria, is predictive of future exacerbation risk and time to the next exacerbation. The concept of control can be used in clinical practice at each clinical visit as a complement to the current recommendations of initial treatment proposed by guidelines.

Increased Chitotriosidase Is Associated With Aspergillus and Frequent Exacerbations in South-East Asian Patients With Bronchiectasis.

BACKGROUND: Chitinase activity is an important innate immune defence mechanism against infection that includes fungi. The 2 human chitinases: chitotriosidase (CHIT1) and acidic mammalian chitinase are associated to allergy, asthma, and COPD; however, their role in bronchiectasis and bronchiectasis-COPD overlap (BCO) is unknown. 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.

"High-Risk" Clinical and Inflammatory Clusters in COPD of Chinese Descent.

BACKGROUND: COPD is a heterogeneous disease demonstrating inter-individual variation. A high COPD prevalence in Chinese populations is described, but little is known about disease clusters and prognostic outcomes in the Chinese population across Southeast Asia. We aim to determine if clusters of Chinese patients with COPD exist and their association with systemic inflammation and clinical outcomes. RESEARCH QUESTION: We aim to determine if clusters of Chinese patients with COPD exist and their association with clinical outcomes and inflammation. STUDY DESIGN AND METHODS: Chinese patients with stable COPD were prospectively recruited into two cohorts (derivation and validation) from six hospitals across three Southeast Asian countries (Singapore, Malaysia, and Hong Kong; n = 1,480). Each patient was followed more than 2 years. Clinical data (including co-morbidities) were employed in unsupervised hierarchical clustering (followed by validation) to determine the existence of patient clusters and their prognostic outcome. Accompanying systemic cytokine assessments were performed in a subset (n = 336) of patients with COPD to determine if inflammatory patterns and associated networks characterized the derived clusters. RESULTS: Five patient clusters were identified including: (1) ex-TB, (2) diabetic, (3) low comorbidity: low-risk, (4) low comorbidity: high-risk, and (5) cardiovascular. The cardiovascular and ex-TB clusters demonstrate highest mortality (independent of Global Initiative for Chronic Obstructive Lung Disease assessment) and illustrate diverse cytokine patterns with complex inflammatory networks. INTERPRETATION: We describe clusters of Chinese patients with COPD, two of which represent high-risk clusters. The cardiovascular and ex-TB patient clusters exhibit high mortality, significant inflammation, and complex cytokine networks. Clinical and inflammatory risk stratification of Chinese patients with COPD should be considered for targeted intervention to improve disease outcomes.