Search

Marcus Sim,1 Anthony Yii,1 Xiaomeng Xu,2 Priti Bahety,3 Chee Hong Loh,1 Aldo Amador Navarro Rojas,4 Dominique Milea,2 Augustine Tee1 1Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore, Singapore; 2Value Evidence & Outcomes, Greater China and Intercontinental, GSK, Singapore, Singapore; 3Medical Affairs, GSK, Singapore, Singapore; 4Respiratory & Specialty Medical Lead, Greater China and Intercontinental, GSK, Singapore, SingaporeCorrespondence: Marcus Sim, Department of Respiratory and Critical Care Medicine, Changi General Hospital, 2 Simei Street 3, Singapore, 529889, Singapore, Tel +65 6788 8833, Email marcus.sim@mohh.com.sgIntroduction: 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 β2-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.Keywords: COPD treatment, database analysis, dual bronchodilator, LABA, LAMA, inhaler prescription

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.

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.

INTRODUCTION: The Rapid Response System for recognising and responding to clinically deteriorating patients has been progressively implemented in acute care hospitals across the globe. This study sought to review the implementation of this system in acute public hospitals in Singapore. METHODS: A cross-sectional study using a face-to-face survey questionnaire was conducted. RESULTS: Five out of seven invited hospitals completed the questionnaire and rated the Rapid Response System as either high priority or essential, and indicated its importance over other patient safety indicators. Sensitivity and specificity of the triggering criteria and non-adherence to the escalation protocol were highlighted issues. Only two hospitals had a dedicated response team for providing emergency help to deteriorating ward patients. Limited manpower resources, unclear roles between the primary and response teams, and the potential deskilling of ward staff were reported barriers that inhibited the uptake of a response team. All hospitals had a committee that oversaw its system operation, provided training to ward staff, and used information technology to support the implementation. CONCLUSION: A variety of approaches have been taken to support the system of recognising and responding to clinical deterioration. This calls for a national approach to enable the standardisation of clinical processes, sharing of educational resources and multi-site evaluation.

Background Despite the widespread implementation of medical emergency teams (METs) in hospitals to provide immediate interventions to deteriorating ward patients, little is known about how junior doctors and nurses escalate care for deteriorating ward patients in hospitals with established MET services. Objectives The objective of this research study was to explore the experiences of junior doctors and nurses in escalating care for clinically deteriorating patients in general wards. Methods Twenty-four individual interviews were conducted with 10 junior doctors and 14 registered nurses of a 1000-bed acute general hospital with the most established MET service in Singapore. Interviews were transcribed verbatim and analysed using an interpretive thematic analysis approach. Findings Three salient themes emerged from thematic analysis: (1) MET activations versus the primary team doctors' reviews, (2) challenges in obtaining medical reviews, and (3) unspoken rules of the escalation of care. Participants' decisions to call the MET or to escalate to the primary team doctors not only depended on the severity of a patient's deterioration and their perceptions of the primary team doctors' capacity to manage the patient but also were largely influenced by sociocultural factors that were shaped by the hierarchy of medical professions. Key challenges faced by nurses in obtaining medical reviews from junior doctors for patients with early deterioration included presenting “convincing” evidence of patient deterioration and “packaging” information about patient deterioration. Conclusions The decision to call a MET or the primary team doctors is a complex judgement that is greatly influenced by the dynamics of perceived hierarchy between the medicine and nursing professions and within the medicine profession. Educational and organisational changes that enhance doctor–nurse interprofessional and intraprofessional collaboration among all levels of doctors may improve the process of the escalation of care for deteriorating patients and thus improve patient safety for hospitalised patients.

Precision medicine is playing an increasingly important role in cancer management and treatment. Specifically in the field of oncology, circulating tumor cells (CTCs) hold significant promise in enabling non-invasive prognostication and near real-time monitoring to individualize treatments. In this study, we present strong associations between CTC subtype counts with treatment response and tumor staging in lung, nasopharyngeal and breast cancers. Longitudinal analysis of CTC count changes over short-time windows further reveals the ability to predict treatment response close to real-time. Our findings demonstrate the suitability of CTCs as a definitive blood-based metric for continuous treatment monitoring. Robust processing of high-throughput image data, explainable classification of CTC subtypes and accurate quantification were achieved using an in-house image analysis system ‘CTC-Quant’, which showed excellent agreement with expert opinion upon extensive validation.

BackgroundTissue biopsy is an integral part of the diagnostic approach to lung cancer. It is however invasive and associated with limitations of tissue 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.MethodsPatients with suspected lung cancer (n=71) were prospectively recruited. Blood and diagnostic tissue samples were collected within 48 hrs 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, where available (tissueEGFRtesting). Concordance of clinically actionable mutations between methods and sample types were assessed.ResultsFor confirmed NSCLC cases (n = 54), tissueEGFRtest results were available only for 70.3% (38/54) due to sample inadequacies, compared to blood samples for 98.1% (53/54) cases. TissueEGFRtesting identified sensitizingEGFR(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, includingEGFRmutations in two cases with no tissue EGFR results, and mutations inKRAS, BRAFandMET. Overall sensitivity ofEGFRsensitizing mutation detection by plasma NGS was 75% (9/12), and specificity was 100% (25/25) in patients tested in both tissueEGFRand plasma NGS (n=37). In this cohort of patients, tissueEGFRtesting alone informed clinical decisions in 22.2% (12/54) of cases. Adding plasma NGS to tissueEGFRtesting increased the detection rate of actionable mutations to 42.6% (23/54), representing a near doubling (1.9-fold increase) of clinically relevant findings. The average turnaround time (TAT) of plasma NGS was shorter than standard tissue testing (10 days vs. 29.9 days, p-value ConclusionsIn the first-line setting, plasma NGS was highly concordant with tissueEGFRtesting. Plasma NGS increases the detection of actionable findings with shorter time to results. This study outlines the clinical utility of a complementary plasma mutation profiling in the routine management of lung cancer patients.

We aimed to compare clinical characteristics between Asian and Western chronic obstructive pulmonary disease (COPD) patients. This was a sub-analysis of an international, multicenter, prospective cohort study. Asian patients were enrolled in Singapore and South Korea. Western patients were enrolled in Spain, Poland, Ireland, the United Kingdom, and Malta. A total of 349 patients were analyzed. Among them, 110 (32%) patients were Asian and 239 (68%) Western. Male sex was more predominant in Asian than in Western (95% versus 63%, respectively; P

Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non–cystic fibrosis bronchiectasis remain unclear. Objectives: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis. Methods: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles (“immunoallertypes”), were determined. Measurements and Main Results: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. “Sensitized bronchiectasis” was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome. Conclusions: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a “treatable trait” permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials. Ministry of Education (MOE) Ministry of Health (MOH) National Medical Research Council (NMRC) Published version Supported by the Singapore Ministry of Health’s National Medical Research Council under its Transition Award NMRC/TA/0048/2016 (S.H.C.) and Changi General Hospital Research grant CHF2016.03-P (T.B.L.). The work performed at NUS was supported by the Singapore Ministry of Education Academic Research Fund, SIgN, and National Medical Research Council grants N-154-000-038-001, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, SIgN-06-006, SIgN-08-020, and NMRC/1150/2008 (F.T.C.); J.D.C. is supported by the GSK/British Lung Foundation Chair of Respiratory Research.

Background Assessing risk of future exacerbations is an important component in COPD management. History of exacerbation is a strong and independent predictor of future exacerbations, and the criterion of ≥2 nonhospitalized or ≥1 hospitalized exacerbation is often used to identify high-risk patients in whom therapy should be intensified. However, other factors or "treatable traits" also contribute to risk of exacerbation. Objective The objective of the study was to develop and externally validate a novel clinical prediction model for risk of hospitalized COPD exacerbations based on both exacerbation history and treatable traits. Patients and methods A total of 237 patients from the COPD Registry of Changi General Hospital, Singapore, aged 75±9 years and with mean post-bronchodilator FEV1 60%±20% predicted, formed the derivation cohort. Hospitalized exacerbation rate was modeled using zero-inflated negative binomial regression. Calibration was assessed by graphically comparing the agreement between predicted and observed annual hospitalized exacerbation rates. Predictive (discriminative) accuracy of the model for identifying high-risk patients (defined as experiencing ≥1 hospitalized exacerbations) was assessed with area under the curve (AUC) and receiver operating characteristics analyses, and compared to other existing risk indices. We externally validated the prediction model using a multicenter dataset comprising 419 COPD patients. Results The final model included hospitalized exacerbation rate in the previous year, history of acute invasive/noninvasive ventilation, coronary artery disease, bronchiectasis, and sputum nontuberculous mycobacteria isolation. There was excellent agreement between predicted and observed annual hospitalized exacerbation rates. AUC was 0.789 indicating good discriminative accuracy, and was significantly higher than the AUC of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) risk assessment criterion (history of ≥1 hospitalized exacerbation in the previous year) and the age, dyspnea, and obstruction index. When applied to the independent multicenter validation cohort, the model was well-calibrated and discrimination was good. Conclusion We have derived and externally validated a novel risk prediction model for COPD hospitalizations which outperforms several other risk indices. Our model incorporates several treatable traits which can be targeted for intervention to reduce risk of future hospitalized exacerbations.

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. Ministry of Education (MOE) Ministry of Health (MOH) National Medical Research Council (NMRC) Published version This research is supported by the Singapore General Hospital Research Grant (SRG-OPN-06-2021) (P.Y. Tiew) and the Singapore Ministry of Health's National Medical Research Council under its Clinician-Scientist Individual Research Grant (MOH-000141) (S.H. Chotirmall) and Clinician-Scientist Award (MOH-000710) (S.H. Chotirmall). K. Tsaneva-Atanasova gratefully acknowledges the financial support of the EPSRC via grant EP/T017856/1. F.T. Chew (Singapore) received grants from the National University of Singapore (N-154-000-038-001), Singapore Ministry of Education Academic Research Fund (R-154-000-191-112, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, R-154-000-A91-592, R-154-000-A95-592, R154-000-B99-114), Biomedical Research Council (Singapore) (BMRC/01/1/21/18/077, BMRC/04/1/21/19/315, BMRC/APG2013/108), Singapore Immunology Network (SIgN-06-006, SIgN-08-020), National Medical Research Council (Singapore) (NMRC/1150/2008), and the Agency for Science Technology and Research (Singapore) (H17/01/a0/008 and APG2013/108). Funding information for this article has been deposited with the Crossref Funder Registry.

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.

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. Ministry of Health (MOH) Nanyang Technological University This research is supported by the Singapore Ministry of Health's National Medical Research Council under its Transition Award (NMRC/TA/0048/2016 to S.H.C.); the Clinician-Scientist Individual Research Grant (MOH-000141 to S.H.C.); NTU Integrated Medical, Biological and Environmental Life Sciences (NIMBELS) (NIM/03/2018 to S.H.C.); the British Lung Foundation through the GSK/British Lung Foundation Chair of Respiratory Research (to J.D.C.) and the Scottish Government Chief Scientist Office (SCAF/17/03). K.T.-A. gratefully acknowledges the financial support of the EPSRC via grant EP/N014391/1.

Lung function classifies respiratory diseases. However, obtaining them with spirometry is difficult. We present an easy method that combines breathing patterns and machine learning to classify healthy from respiratory conditions at accuracy of 97.7%.

Background: A lack of study on the COPD mycobiome exists. Methods: We performed the largest multicenter evaluation of the COPD mycobiome including patients from Asia (Singapore and Malaysia) and the UK (Scotland) (n=380). Non-diseased controls (n=47) were assessed and longitudinal analyses performed during and following exacerbations (n=34). COPD mycobiomes were examined based on mortality and occurrence of serum specific-IgE against selected fungi. Results: A distinct mycobiome profile in COPD evidenced by increased α-diversity (p Conclusion: Frequent COPD exacerbators are characterized by Aspergillus, Penicillium and Curvularia and illustrate poorer survival and systemic specific-IgE responses against these fungi allowing COPD risk stratification based on airway mycobiomes. Funding: Singapore Ministry of Health’s National Medical Research Council under its Research Training Fellowship (NMRC/Fellowship/0049/2017) (P.Y.T) and Clinician-Scientist Individual Research Grant (MOH-000141) (S.H.C). The TARDIS study is funded by Glaxosmithkline & British Lung Foundation (Fellowship to JDC).

Background: To date, no study has integrated bacterial, viral and fungal microbiomes to provide a holistic assessment of the true in-vivo state. Methods: We report the first integrated ‘multi-biome’ analysis integrating bacteriome, virome and mycobiomes in bronchiectasis (n=217) employing weighted Similarity Network Fusion coupled to co-occurrence network analysis to evaluate the ‘interactome’. Interactome dynamics at baseline, during exacerbations and following recovery was assessed in n=17 patients with bronchiectasis. Results: “Integrative microbiomics” identifies patients at high-risk of exacerbation. Frequent exacerbators exhibit reduced α-diversity and elevated antagonistic interactions. Assessment of the Pseudomonas-interactome reveals that its network rather than abundance is key in determining exacerbation risk. Longitudinal ‘interactome’ analysis reveals increased antagonistic interactions during exacerbations which resolve following treatment within an otherwise stable microbiome. The interactome has ‘core’ and ‘ancillary’ components, the latter altered during exacerbation. Conclusion: “Integrative microbiomics” captures interactions determining exacerbation risk otherwise unaccounted by specific microbes. Antibiotic strategies likely target interaction networks rather than individual microbes providing fresh approaches to understanding respiratory infection. Funding: Singapore Ministry of Health’s National Medical Research Council under its Transition Award (NMRC/TA/0048/2016) (S.H.C); Clinician-Scientist Individual Research Grant (MOH-000141) (S.H.C) and the NTU Integrated Medical, Biological and Environmental Life Sciences (NIMBELS) [NIM/03/2018] (S.H.C).

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.

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.

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.

Background Medical Emergency Teams (MET) have been implemented in many hospitals to improve patient safety. Few studies examined how residents perceive the MET as part of training. Objective We aimed to evaluate residents’ perceptions of how MET rotation affected training in the core competencies specified by Accreditation Council for Graduate Medical Education (ACGME). Methods We conducted an online survey of 106 residents. They are either junior residents who are in training in internal medicine, non-trainee registrars or senior residents who are training in respiratory or advanced internal medicine. Results We achieved a response rate of 62.3%. More than 90% of residents agreed or strongly agreed that MET contributed positively to their training, made resuscitation of patients safer and more efficient, and disagreed or strongly disagreed that MET made resuscitation of patients more time-consuming or cumbersome. More than 80% agreed or strongly agreed that the MET improved their clinical judgement in medical emergencies, helped achieve their learning goals and exposed them to a wide variety of cases. At least two-thirds thought that the MET posting improved their procedural skills and communication in end of life care discussions. In contrast, 26.6% of respondents agreed or strongly agreed that the MET decreased autonomy of the primary team. One-third felt they needed formal training for the MET posting. Conclusion Our findings suggest that residents perceive participation in MET was beneficial in training and improved patient care. We also found that formal training and consultant oversight may be needed for junior team leaders of MET.

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.

United airways disease (UAD) is the concept that the upper and lower airways, which are anatomically and immunologically related, form a single organ. According to this concept, upper and lower airway diseases are frequently comorbid because they reflect manifestations of a single underlying disease at different sites of the respiratory tract. Allergic asthma-allergic rhinitis is the archetypal UAD, but emerging data indicate that UAD is a heterogeneous condition and consists of multiple phenotypes (observable clinical characteristics) and endotypes (pathobiologic mechanisms). The UAD paradigm also extends to myriad sinonasal diseases (eg, chronic rhinosinusitis with or without nasal polyps) and lower airway diseases (eg, bronchiectasis, chronic obstructive pulmonary disease). Here, we review currently known phenoendotypes of UAD and propose a "treatable traits" approach for the classification and management of UAD, wherein pathophysiological mechanisms and factors contributing to disease are identified and targeted for treatment. Treatable traits in UAD can be analyzed according to a framework comprising airway inflammation (eosinophilic, neutrophilic), impaired airway mucosal defense (impaired mucociliary clearance, antibody deficiency), and exogenous cofactors (allergic sensitizers, tobacco smoke, microbes). Appreciation of treatable traits is necessary in advancing the effort to deliver precise treatments and achieve better outcomes in patients with UAD.

Exacerbations are important outcomes in asthma. Risk factors for exacerbations may differ in different populations. Although various demographic and clinical variables were examined in previous studies on exacerbation risks in asthma, important variables such as ethnicity, adherence, and medication titration were not included. This study examined independent predictors of future exacerbations in a multi-ethnic asthma population in Asia, while including the variables of ethnicity, medication adherence, and medication change in our analysis.We recruited patients with physician-diagnosed asthma in a tertiary hospital in Singapore over a one-year period. Exacerbations requiring ≥3 days of systemic corticosteroids one year prior to study enrolment (previous exacerbations) and the year following enrolment (future exacerbations) were recorded from electronic medical records. Medication adherence was based on pharmacy refill. An increase or a decrease in the Global Initiative for Asthma treatment steps were considered to be medication up- and down-titration, respectively. A multivariate logistic regression model was constructed to determine independent predictors of future exacerbations.The study cohort of 340 patients comprised mainly of Chinese (53.2%), Malay (32.9%), and Indian (9.7%) ethnicities. After multivariate analysis, only Indian ethnicity (OR 3.75, 95% CI 1.077-13.051, p = 0.038), Asthma Control Test score (OR 0.913, 95% CI 0.839-0.995, p = 0.037), and the number of previous exacerbations (OR 1.84, 95% CI 1.416-2.391, p0.001) were independent predictors of future exacerbations.There are ethnic differences in exacerbation risk in Asian populations. Each incremental worsening of the asthma symptom control score and each additional exacerbation also increases the risk of future exacerbations.

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.

IntroductionAllergic sensitisation to fungi such asAspergillusare associated to poor clinical outcomes in asthma, bronchiectasis and cystic fibrosis; however, clinical relevance in COPD remains unclear.MethodsPatients 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.ResultsHigh 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.ConclusionFungal 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.

Introduction In light of the growing evidence base for better clinical results with the use of the dual bronchodilator indacaterol/glycopyrronium (IND/GLY) over inhaled corticosteroid-containing salmeterol/fluticasone combination (SFC), this study aimed to evaluate the cost-effectiveness of IND/GLY over SFC in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) who are at low risk of exacerbations, in the Singapore healthcare setting. Methods A previously published patient-level simulation model was adapted for use in Singapore by applying local unit costs. The model was populated with clinical data from the LANTERN and ECLIPSE studies. Both costs and health outcomes were predicted for the lifetime horizon from a payer's perspective and were discounted at 3% per annum. Costs were expressed in 2015 USD exchange rates. Uncertainty was assessed through probabilistic sensitivity analysis. Results Compared to SFC, use of IND/GLY increased mean life expectancy by 0.316 years and mean quality-adjusted life years (QALYs) by 0.246 years, and decreased mean total treatment costs (drug costs and management of associated events) by USD 1,474 over the entire lifetime horizon. IND/GLY was considered to be 100% cost-effective at a threshold of 1 × gross domestic product per capita. The cost-effectiveness acceptability curve showed that IND/GLY was 100% cost-effective at a willingness-to-pay threshold of USD 0 (additional cost) when compared to SFC. Conclusion IND/GLY was estimated to be highly cost-effective compared to SFC in patients with moderate-to-severe COPD who are not at high risk of exacerbations in the Singapore healthcare setting.

Purpose To synthesize factors influencing the activation of the rapid response system (RRS) and reasons for suboptimal RRS activation by ward nurses and junior physicians. Data sources Nine electronic databases were searched for articles published between January 1995 and January 2016 in addition to a hand-search of reference lists and relevant journals. Study selection Published primary studies conducted in adult general ward settings and involved the experiences and views of ward nurses and/or junior physicians in RRS activation were included. Data extraction Data on design, methods and key findings were extracted and collated. Results of data synthesis Thirty studies were included for the review. The process to RRS activation was influenced by the perceptions and clinical experiences of ward nurses and physicians, and facilitated by tools and technologies, including the sensitivity and specificity of the activation criteria, and monitoring technology. However, the task of enacting the RRS activations was challenged by seeking further justification, deliberating over reactions from the rapid response team and the impact of workload and staffing. Finally, adherence to the traditional model of escalation of care, support from colleagues and hospital leaders, and staff training were organizational factors that influence RRS activation. Conclusion This review suggests that the factors influencing RRS activation originated from a combination of socio-cultural, organizational and technical aspects. Institutions that strive for improvements in the existing RRS or are considering to adopt the RRS should consider the complex interactions between people and the elements of technologies, tasks, environment and organization in healthcare settings.

Chronic obstructive pulmonary disease (COPD) is a condition commonly encountered by primary care practitioners. The disease should be detected in its early stages to prevent disease progression and to reduce the burden of symptoms. Early treatment also results in improved mortality and reduced morbidity. COPD should be differentiated from other similar conditions such as asthma, as the basis of treatment differs in these conditions, and misdiagnosis can lead to poorer patient outcomes. Non-pharmacological treatment such as smoking cessation and vaccinations are important in the management of COPD, while pharmacotherapy such as bronchodilators and antimuscarinics are the mainstay of therapy in COPD. Referral to a specialist is recommended when there is progression of the disease or uncertainty regarding the diagnosis.

Background The purpose of this study was to assess the efficiency of performing pulmonary procedures in the endoscopy unit in a large teaching hospital. Methods A prospective study from May 20 to July 19, 2013, was designed. The main outcome measures were procedure delays and their reasons, duration of procedural steps starting from patient's arrival to endoscopy unit, turnaround time, total case durations, and procedure wait time. Results A total of 65 procedures were observed. The most common procedure was BAL (61%) followed by TBLB (31%). Overall procedures for 35 (53.8%) of 65 patients were delayed by ≥ 30 minutes, 21/35 (60%) because of "spillover" of the gastrointestinal and surgical cases into the time block of pulmonary procedure. Time elapsed between end of pulmonary procedure and start of the next procedure was ≥ 30 minutes in 8/51 (16%) of cases. In 18/51 (35%) patients there was no next case in the room after completion of the pulmonary procedure. The average idle time of the room after the end of pulmonary procedure and start of next case or end of shift at 5:00 PM if no next case was 58 ± 53 minutes. In 17/51 (33%) patients the room's idle time was >60 minutes. A total of 52.3% of patients had the wait time >2 days and 11% had it ≥ 6 days, reason in 15/21 (71%) being unavailability of the slot. Conclusions Most pulmonary procedures were delayed due to spillover of the gastrointestinal and surgical cases into the block time allocated to pulmonary procedures. The most common reason for difficulty encountered in scheduling the pulmonary procedure was slot unavailability. This caused increased procedure waiting time. The strategies to reduce procedure delays and turnaround times, along with improved scheduling methods, may have a favorable impact on the volume of procedures performed in the unit thereby optimizing the existing resources.

Chronic obstructive pulmonary disease (COPD) is the tenth cause of death in Singapore in 2014, and a significant burden to the healthcare system. This study aims to assess current public awareness of COPD at a Singapore mall where a COPD day event is held concurrently. A set of 12 questions adapted from 10-ACAQ (Athens COPD awareness questionnaire) – 4 demographic, 7 COPD-oriented and 1 contextual question – investigated the basic knowledge and awareness of COPD. The subjects were public, aged 18 and above, conveniently sampled during a COPD awareness campaign organized outside a shopping mall on 21 November 2015. A total of 82 males and 78 females were surveyed. 65% have never heard of COPD. Of those 35% who have heard, 90% were not aware that it refers to chronic bronchitis and emphysema while 28% incorrectly identified the commonest symptoms. The awareness level of smokers was lower (9%) compared to non-smokers (35%) – 31% of smokers had the misconception that COPD is pneumonia. Amongst those surveyed, 32.5% were unaware that COPD is a top ten cause of death in Singapore, 25% incorrectly identified COPD as a contagious disease, and 12.5% had the misconception that current or ex-smokers are not at a higher risk of COPD. Our results are comparable to the Athens study conducted in 2002 which found that: out of the 47% surveyed who had heard of COPD, 72% were unaware of what it truly is. In summary, the awareness of COPD in the Singapore public is low, highlighting the need for interventions aimed at educating the public about it. Also, a larger survey sample would also be preferred to validate the findings of this study.

Objective To estimate the prognostic value of point-of-care measurement of biomarkers related to dyspnea in patients receiving a medical emergency team (MET) review. Design Prospective observational study. Setting University affiliated hospital. Patients Cohort of 95 patients receiving MET review over a six month period. Methods We used a commercial multi-biomarker panel for shortness-of-breath (SOB panel) (Biosite Triage Profiler, Biosite Incorporated ® , 9975 Summers Ridge Road, San Diego, CA 92121, USA) including Brain natriuretic peptide (BNP), D-dimer, myoglobin (Myo), creatine kinase MB isoenzyme (CK-MB) and troponin I (Tn-I). We recorded information about demographics, MET review triggers, and MET procedures and patient outcome. Results Mean age was 70.5 (±15) years, 38 (41%) patients had a history of chronic heart failure (CHF) and 67 (70%) chronic kidney disease (CKD). At MET activation, 42 (44%) patients were dyspneic. The multi-biomarker panel was positive for at least one marker in 48 (51%) cases. BNP and D-dimer had a sensitivity of 0.79 and 0.93 for ICU admission with a negative predictive value (NPV) of 0.89 and 0.92 respectively. Thirty-five (37%) patients died. BNP was positive in 85% of such cases with sensitivity and NPV of 0.86 and 0.82, respectively. D-dimer was positive in 77% of non-survivors with a sensitivity and NPV of 0.94 and 0.88, respectively. BNP (area under the curve of receiver operating characteristic curve – AUC-ROC: 0.638) and D-dimer (AUC-ROC: 0.574) achieved poor discrimination of subsequent death. Similar findings applied to ICU admission. The combination of normal BNP and D-dimer levels completely ruled out ICU admission or death. The cardiac part of the panel was not useful in predicting ICU admission or mortality. Conclusions Although, BNP and D-dimer are poor discriminants of ICU admission and hospital mortality, normal BNP and D-dimer levels practically exclude subsequent need for ICU admission and hospital mortality.

There is evidence that aspirin and non-aspirin non-steroidal anti-inflammatory drug (NSAID) have anti-carcinogenic properties, but their effect on lung cancer, in particular in never-smokers, is unclear. Information on past or current use of anti-inflammatory medication was obtained in 398 Chinese female primary lung cancer cases and 814 controls in a hospital-based study in Singapore. 65% of cases and 88% of controls were never-smokers. Controls were excluded if they had been admitted for conditions associated with aspirin or NSAID use (n=174). Regular aspirin use (twice a week or more, for a month or more) was associated with a reduced risk of lung cancer (adjusted odds ratio [OR] 0.50, 95% confidence intervals [95%CI] 0.31-0.81 in non-smokers; OR 0.38, 95%CI 0.16-0.93 in smokers). Regular use of non-aspirin NSAID, paracetamol, steroid creams and steroid pills was uncommon and no association with lung cancer was detected. Our results suggest that aspirin consumption may reduce lung cancer risk in Asian women and are consistent with current understanding of the role of cyclooxygenase in lung carcinogenesis.

The authors examined relations between reproductive factors and 5 estrogen pathway gene polymorphisms (CYP17 rs743572, CYP19A1 rs10046, ERβ rs1256049, ERβ rs4986938, and COMT rs4680) among 702 Singapore Chinese female lung cancer cases and 1,578 hospital controls, of whom 433 cases (61.7%) and 1,375 controls (87.1%) were never smokers. Parity (per child, odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.87, 0.97) and menstrual cycle length (for ≥30 days vs.