Residential exposure to Aspergillus spp. is associated with exacerbations in COPD.

BACKGROUND: Sensitisation to Aspergillus fumigatus is linked to worse outcomes in patients with chronic obstructive pulmonary disease (COPD), however, its prevalence and clinical implications in domestic (residential) settings remains unknown. METHODS: Individuals with COPD (n=43) recruited in Singapore had their residences prospectively sampled and assessed by shotgun metagenomic sequencing including indoor air, outdoor air, and touch surfaces (total: 126 specimens). The abundance of environmental A. fumigatus and the occurrence of A. fumigatus (Asp f) allergens in the environment were determined and immunological responses to A. fumigatus allergens determined in association with clinical outcomes including exacerbation frequency. Findings were validated in 12 individuals (31 specimens) with COPD in Vancouver, Canada, a climatically different region. RESULTS: 157 metagenomes from 43 homes were assessed. Eleven and nine separate Aspergillus spp. were identified in Singapore and Vancouver respectively. Despite climatic, temperature, and humidity variation, A. fumigatus was detectable in the environment from both locations. The relative abundance of environmental A. fumigatus was significantly associated with exacerbation frequency in both Singapore (r=0.27, p=0.003) and Vancouver (r=0.49, p=0.01) and individuals with higher Asp f 3 sensitisation responses lived in homes with a greater abundance of environmental Asp f 3 allergens (p=0.037). Patients exposed and sensitised to Asp f 3 allergens demonstrated a higher rate of COPD exacerbations at 1-year follow-up (p=0.021). CONCLUSION: Environmental A. fumigatus exposure in the home environment including air and surfaces with resulting sensitisation carries pathogenic potential in individuals with COPD. Targeting domestic A. fumigatus abundance may reduce COPD exacerbations.

The association between sleep quantity, insomnia and lung cancer risk - A systematic review and meta-analysis.

PURPOSE: The effect of various sleep traits on the risk of lung cancer differs among pre-existing studies. This study aims to systematically review and synthesise the association between sleep duration and insomnia with the incidence of lung cancer. METHODS: PubMed, Embase and The Cochrane Library were searched from inception to 23 April 2023 for observational studies examining the effect of sleep quantity or insomnia on lung cancer incidence. We pooled maximally-adjusted hazard ratios and odds ratios separately using random effects inverse variance weighted models. The risk of bias of observational studies was assessed using the Newcastle-Ottawa Scale. RESULTS: We included 11 observational studies with a pooled cohort of 5,049,141 patients. The mean age of the patients was 49.5 ± 17.7 years, and 51.4% were males. The risk of bias ranged from low-moderate. Individuals who slept for a shorter or longer duration than the reference range of sleep per night showed an increased risk of lung cancer by 11% (HR:1.11; 95%CI:1.00-1.23) and 16% (HR:1.16; 95%CI:1.06-1.27) respectively. Furthermore, individuals with insomnia symptoms had a 9% greater risk of lung cancer than those without symptoms (HR:1.09; 95%CI:1.05-1.13). CONCLUSION: This study suggests that insufficient sleep, excessive sleep and insomnia may be associated with an increased risk of lung cancer. Physicians should be mindful of this association and encourage healthy sleep practises among patients. Given the observed heterogeneity among some pre-existing studies, future research with longer periods of follow-up, greater control for covariates and objective testing of sleep parameters may add value to this topic.

Metagenomics Reveals a Core Macrolide Resistome Related to Microbiota in Chronic Respiratory Disease.

Rationale: Long-term antibiotic use for managing chronic respiratory disease is increasing; however, the role of the airway resistome and its relationship to host microbiomes remains unknown.Objectives: To evaluate airway resistomes and relate them to host and environmental microbiomes using ultradeep metagenomic shotgun sequencing.Methods: Airway specimens from 85 individuals with and without chronic respiratory disease (severe asthma, chronic obstructive pulmonary disease, and bronchiectasis) were subjected to metagenomic sequencing to an average depth exceeding 20 million reads. Respiratory and device-associated microbiomes were evaluated on the basis of taxonomical classification and functional annotation including the Comprehensive Antibiotic Resistance Database to determine airway resistomes. Co-occurrence networks of gene-microbe association were constructed to determine potential microbial sources of the airway resistome. Paired patient-inhaler metagenomes were compared (n = 31) to assess for the presence of airway-environment overlap in microbiomes and/or resistomes.Measurements and Main Results: Airway metagenomes exhibit taxonomic and metabolic diversity and distinct antimicrobial resistance patterns. A "core" airway resistome dominated by macrolide but with high prevalence of ß-lactam, fluoroquinolone, and tetracycline resistance genes exists and is independent of disease status or antibiotic exposure. Streptococcus and Actinomyces are key potential microbial reservoirs of macrolide resistance including the ermX, ermF, and msrD genes. Significant patient-inhaler overlap in airway microbiomes and their resistomes is identified where the latter may be a proxy for airway microbiome assessment in chronic respiratory disease.Conclusions: Metagenomic analysis of the airway reveals a core macrolide resistome harbored by the host microbiome.

Distinct "Immunoallertypes" of Disease and High Frequencies of Sensitization in Non-Cystic Fibrosis Bronchiectasis.

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.

Choosing the right mask for your Asian patient with sleep apnoea: A randomized, crossover trial of CPAP interfaces.

BACKGROUND AND OBJECTIVE: A major challenge with the treatment of obstructive sleep apnoea (OSA) is adherence to continuous positive airway pressure (CPAP) therapy. Mask tolerability is an important determinant of adherence, however evidence to guide selection of mask interfaces is lacking. METHODS: We conducted a randomized crossover trial of mask interfaces in CPAP therapy for moderate-to-severe OSA to assess adherence and efficacy of CPAP therapy with nasal mask, nasal pillow and oronasal masks. Demographic data, Nasal Obstruction Symptom Evaluation (NOSE) scores and craniofacial measurements were also analysed for associations with adherence with oronasal masks. RESULTS: Eighty-five patients were included in the study (mean ± SD age: 46 ± 12 years; body mass index: 29.9 ± 5.6 kg/m2 ; apnoea-hypopnoea index (AHI): 53.6 ± 24.0 events/h). Patients had better adherence with nasal masks (average night use: 3.96 ± 2.26 h/night) compared to oronasal masks (3.26 ± 2.18 h/night, P < 0.001) and nasal pillows (3.48 ± 2.20 h/night, P = 0.007). Residual AHI was higher with oronasal masks (7.2 ± 5.2) compared to nasal masks (4.0 ± 4.2, P < 0.001) and nasal pillows (4.1 ± 3.3, P < 0.001). Twenty-two (25.9%) patients had the best adherence with oronasal masks (4.22 ± 2.14 vs 2.93 ± 2.12 h/night, P = 0.016). These patients had lower NOSE scores (15 (0-35) vs 40 (10-55), P = 0.024) and larger menton-labrale inferioris/biocular width ratios (31 ± 3% vs 28 ± 4%, P = 0.019). CONCLUSION: Nasal masks are the preferred interface during CPAP initiation. Patients with less nasal obstruction and a proportionally increased chin-lower lip distance to mid-face width may have better CPAP adherence with an oronasal mask interface.

Immunological corollary of the pulmonary mycobiome in bronchiectasis: the CAMEB study.

Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a "research priorities" consensus statement for bronchiectasis.Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S-28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes.The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus, Cryptococcus and ClavisporaAspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus-associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations.The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus-associated disease should be considered even in apparently stable patients.

Obstructive Sleep Apnea and Cardiovascular Events After Percutaneous Coronary Intervention.

BACKGROUND: There is a paucity of data from large cohort studies examining the prognostic significance of obstructive sleep apnea (OSA) in patients with coronary artery disease. We hypothesized that OSA predicts subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention. METHODS AND RESULTS: The Sleep and Stent Study was a prospective, multicenter registry of patients successfully treated with percutaneous coronary intervention in 5 countries. Between December 2011 and April 2014, 1748 eligible patients were prospectively enrolled. The 1311 patients who completed a sleep study within 7 days of percutaneous coronary intervention formed the cohort for this analysis. Drug-eluting stents were used in 80.1% and bioresorbable vascular scaffolds in 6.3% of the patients, and OSA, defined as an apnea-hypopnea index of ≥15 events per hour, was found in 45.3%. MACCEs, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned revascularization, occurred in 141 patients during the median follow-up of 1.9 years (interquartile range, 0.8 years). The crude incidence of an MACCEs was higher in the OSA than the non-OSA group (3-year estimate, 18.9% versus 14.0%; p=0.001). Multivariate Cox regression analysis indicated that OSA was a predictor of MACCEs, with an adjusted hazard ratio of 1.57 (95% confidence interval, 1.10-2.24; P=0.013), independently of age, sex, ethnicity, body mass index, diabetes mellitus, and hypertension. CONCLUSIONS: OSA is independently associated with subsequent MACCEs in patients undergoing percutaneous coronary intervention. Evaluation of therapeutic approaches to mitigate OSA-associated risk is warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01306526.

Effects of Ethnicity on the Prevalence of Obstructive Sleep Apnoea in Patients with Acute Coronary Syndrome: A Pooled Analysis of the ISAACC Trial and Sleep and Stent Study.

BACKGROUND: Obstructive sleep apnoea (OSA) is an emerging risk factor for acute coronary syndrome (ACS). We sought to determine the effects of ethnicity on the prevalence of OSA in patients presenting with ACS who participated in an overnight sleep study. METHODS: A pooled analysis using patient-level data from the ISAACC Trial and Sleep and Stent Study was performed. Using the same portable diagnostic device, OSA was defined as an apnoea-hypopnoea index of ≥15 events per hour. RESULTS: A total of 1961 patients were analysed, including Spanish (53.6%, n=1050), Chinese (25.5%, n=500), Indian (12.0%, n=235), Malay (6.1%, n=119), Brazilian (1.7%, n=34) and Burmese (1.2%, n=23) populations. Significant differences in body mass index (BMI) were found among the various ethnic groups, averaging from 25.3kg/m2 for Indians and 25.4kg/m2 for Chinese to 28.6kg/m2 for Spaniards. The prevalence of OSA was highest in the Spanish (63.1%), followed by the Chinese (50.2%), Malay (47.9%), Burmese (43.5%), Brazilian (41.2%), and Indian (36.1%) patients. The estimated odds ratio of BMI on OSA was highest in the Chinese population (1.17; 95% confidence interval: 1.10-1.24), but was not significant in the Spanish, Burmese or Brazilian populations. The area under the curve (AUC) for the Asian patients (ranging from 0.6365 to 0.6692) was higher than that for the Spanish patients (0.5161). CONCLUSION: There was significant ethnic variation in the prevalence of OSA in patients with ACS. The magnitude of the effect of BMI on OSA was greater in the Chinese population than in the Spanish patients.

Optimal Body Mass Index Cut-offs for Identification of Patients with Coronary Artery Disease at High Risk of Obstructive Sleep Apnoea.

BACKGROUND: We sought to evaluate the relationship between Body Mass Index (BMI) and obstructive sleep apnoea (OSA) in Chinese patients hospitalised with coronary artery disease, and to determine the optimal BMI cut-off for prediction of OSA. METHODS: Consecutive Chinese patients who were hospitalised with symptomatic coronary artery disease were recruited to undergo an in-hospital sleep study. RESULTS: A total of 587 patients were recruited. Using cut-off for Asians, 81.2% of the cohort was overweight (BMI ≥23kg/m(2)) and 31.6% was obese (≥27kg/m(2)). A total of 59.5% was diagnosed with OSA, defined as apnoea-hypopnoea index ≥15. Body mass index, hypertension and smoking were predictors of OSA. Multiple logistic regression analysis showed that BMI remains an independent predictor of OSA (odds ratio: 1.11 [95% confidence interval: 1.06 to 1.17], p<0.001) after adjusting for smoking and hypertension. Further analysis using BMI and Apnoea-Hypopnoea Index (AHI) as continuous variables showed significant correlation between BMI and AHI (Pearson's r =0.25, P<0.001). In adjusted models, optimal BMI cut-offs to screen for OSA were 27.3kg/m(2), 23.0-23.9kg/m(2), and 20kg/m(2) for patients with neither, either, or both predictors (smoking and hypertension) respectively. The area under the curve for the adjusted and unadjusted models were similar (0.6013 vs 0.6262, p=0.118). CONCLUSIONS: Body mass index represents a convenient and readily available tool for bedside identification of patients at high risk of OSA. Body mass index cut-offs to predict risks of OSA in Chinese patients with symptomatic coronary artery disease are defined in this study.

A machine learning approach for the diagnosis of obstructive sleep apnoea using oximetry, demographic and anthropometric data.

Introduction: Obstructive sleep apnoea (OSA) is a serious but underdiagnosed condition. Demand for the gold standard diagnostic polysomnogram (PSG) far exceeds its availability. More efficient diagnostic methods are needed, even in tertiary settings. Machine learning (ML) models have strengths in disease prediction and early diagnosis. We explored the use of ML with oximetry, demographic and anthropometric data to diagnose OSA. Methods: A total of 2,996 patients were included for modelling and divided into test and training sets. Seven commonly used supervised learning algorithms were trained with the data. Sensitivity (recall), specificity, positive predictive value (PPV) (precision), negative predictive value, area under the receiver operating characteristic curve (AUC) and F1 measure were reported for each model. Results: In the best performing four-class model (neural network model predicting no, mild, moderate or severe OSA), a prediction of moderate and/or severe disease had a combined PPV of 94%; one out of 335 patients had no OSA and 19 had mild OSA. In the best performing two-class model (logistic regression model predicting no-mild vs. moderate-severe OSA), the PPV for moderate-severe OSA was 92%; two out of 350 patients had no OSA and 26 had mild OSA. Conclusion: Our study showed that the prediction of moderate-severe OSA in a tertiary setting with an ML approach is a viable option to facilitate early identification of OSA. Prospective studies with home-based oximeters and analysis of other oximetry variables are the next steps towards formal implementation.

Obstructive Sleep Apnea and Lung Cancer: A Systematic Review and Meta-Analysis.

Rationale: In 2020, lung cancer was the leading cause of cancer deaths and the most common cancer in men. Although obstructive sleep apnea (OSA) has been postulated to be carcinogenic, epidemiological studies are inconclusive. Objectives: To investigate the associations between OSA and the incidence and mortality of lung cancer. Methods: Four electronic databases (PubMed, Embase, Cochrane Library, and Scopus) were searched from inception until 6 June 2021 for randomized controlled trials and observational studies examining the association between sleep apnea and incident lung cancer. Two reviewers selected studies, extracted data, graded the risk of bias using the Newcastle-Ottawa scale and the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Random-effects models were used to meta-analyze the maximally covariate-adjusted associations. Results: Seven studies were included in our systematic review, among which four were suitable for meta-analysis, comprising a combined cohort of 4,885,518 patients. Risk of bias was low to moderate. OSA was associated with a higher incidence of lung cancer (hazard ratio, 1.25; 95% confidence interval, 1.02-1.53), with substantial heterogeneity (I2 = 97%). Heterogeneity was eliminated, with a stable pooled effect size, when including the three studies with at least 5 years of median follow-up (hazard ratio, 1.32; 95% confidence interval, 1.27-1.37; I2 = 0%). Conclusions: In this meta-analysis of 4,885,518 patients from four observational studies, patients with OSA had an approximately 30% higher risk of lung cancer compared with those without OSA. We suggest more clinical studies with longer follow-up as well as biological models of lung cancer be performed to further elucidate this relationship.

Asian Pacific Society of Cardiology Consensus Statements on the Diagnosis and Management of Obstructive Sleep Apnoea in Patients with Cardiovascular Disease.

Obstructive sleep apnoea (OSA) is strongly associated with cardiovascular disease (CVD). However, evidence supporting this association in the Asian population is scarce. Given the differences in the epidemiology of CVD and cardiovascular risk factors, as well as differences in the availability of healthcare resources between Asian and Western countries, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the management of OSA in patients with CVD in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were in support of 'agree' or 'neutral.' The resulting statements provide guidance on the assessment and treatment of OSA in patients with CVD in the Asia-Pacific region. The APSC hopes for these recommendations to pave the way for screening, early diagnosis and treatment of OSA in the Asia-Pacific region.

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.

Neisseria species as pathobionts in bronchiectasis.

Neisseria species are frequently identified in the bronchiectasis microbiome, but they are regarded as respiratory commensals. Using a combination of human cohorts, next-generation sequencing, systems biology, and animal models, we show that bronchiectasis bacteriomes defined by the presence of Neisseria spp. associate with poor clinical outcomes, including exacerbations. Neisseria subflava cultivated from bronchiectasis patients promotes the loss of epithelial integrity and inflammation in primary epithelial cells. In vivo animal models of Neisseria subflava infection and metabolipidome analysis highlight immunoinflammatory functional gene clusters and provide evidence for pulmonary inflammation. The murine metabolipidomic data were validated with human Neisseria-dominant bronchiectasis samples and compared with disease in which Pseudomonas-, an established bronchiectasis pathogen, is dominant. Metagenomic surveillance of Neisseria across various respiratory disorders reveals broader importance, and the assessment of the home environment in bronchiectasis implies potential environmental sources of exposure. Thus, we identify Neisseria species as pathobionts in bronchiectasis, allowing for improved risk stratification in this high-risk group.

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.

Simplifying STOP-BANG: use of a simple questionnaire to screen for OSA in an Asian population.

OBJECTIVE: We aim to assess the utility of a simple-to-use 8-point questionnaire in screening for moderate-severe obstructive sleep apnea (OSA) and to assess the validity of cutoffs used to score body mass index (BMI) in this questionnaire. METHODS: Patients undergoing diagnostic polysomnography (PSG) were asked to fill in a questionnaire with a simple dichotomized 8-point questionnaire, represented by the mnemonic STOP-BANG. A score of 3 or more out of a possible 8 was taken to indicate high risk for presence of OSA. These were then evaluated versus results from the overnight, monitored PSG. RESULTS: Three hundred and forty-eight patients underwent overnight diagnostic PSG, of whom 319 (91.2%) completed the questionnaire. Seventy-four (22.7%) were classified as being at low risk of OSA and 252 (77.3%) were classified as being high risk. The sensitivities of the STOP-BANG screening tool for an AHI of >5, >15, and >30 were 86.1%, 92.8%, and 95.6%, respectively, with negative predictive values of 84.5% and 93.4% for moderate and severe OSA, respectively. Using cutoffs of 30 or 35 for scoring the BMI did not significantly change the performance of the screening tool. CONCLUSION: STOP-BANG is a clinically useful tool with high sensitivity that can be used to screen patients for moderate and severe OSA. Using cutoffs of 30 for BMI, 40 cm for neck circumference, and 50 years for age simplifies the application of the tool without affecting performance.

Conducting a high-stakes OSCE in a COVID-19 environment.

This article was migrated. The article was marked as recommended. The COVID-19 pandemic has presented significant challenges for medical schools. It is critical to ensure final year medical school students are not delayed in their entry to the clinical workforce in times of healthcare crisis. However, proceeding with assessment to determine competency for graduation from medical school, and maintaining performance standards for graduating doctors is an unprecedented challenge under pandemic conditions. This challenge is hitherto uncharted territory for medical schools and there is scant guidance for medical educators. In early March 2020, Duke-National University Singapore Medical School embraced the challenge for ensuring competent final year medical students could complete their final year of studies and graduate on time, to enter the medical workforce in Singapore without delay. This paper provides details of how the final year clinical performance examinations were planned and conducted during the COVID-19 pandemic. The aim of the paper is to provide guidance to other medical schools in similar circumstances who need to plan and make suitable adjustments to clinical skills examinations under current pandemic conditions. The paper illustrates how it is possible to design and implement clinical skills examinations (OSCEs) to ensure the validity and reliability of high-stakes performance assessments whilst protecting the safety of all participants, minimising risk and maintaining defensibility to key stakeholders.

Early prediction of high flow nasal cannula therapy outcomes using a modified ROX index incorporating heart rate.

BACKGROUND: The ROX index (ratio of pulse oximetry/FIO2 to respiratory rate) has been validated to predict high flow nasal cannula therapy (HFNC) outcomes in patients with pneumonia. We evaluated a modified ROX index incorporating heart rate (HR) in patients initiated on HFNC for acute hypoxemic respiratory failure and as a preventative treatment following planned extubation. METHODS: We performed a prospective observational cohort study of 145 patients treated with HFNC. ROX-HR index was defined as the ratio of ROX index over HR (beats/min), multiplied by a factor of 100. Evaluation was performed using area under the receiving operating characteristic curve (AUROC) and cutoffs assessed for prediction of HFNC failure: defined as the need for mechanical ventilation. RESULTS: Ninety-nine (68.3%) and 46 (31.7%) patients were initiated on HFNC for acute hypoxemic respiratory failure and following a planned extubation, respectively. The majority (86.9%) of patients had pneumonia as a primary diagnosis, and 85 (56.6%) patients were immunocompromised. Sixty-one (42.1%) patients required intubation (HFNC failure). Amongst patients on HFNC for acute respiratory failure, HFNC failure was associated with a lower ROX and ROX-HR index recorded at time points between 1 and 48 h. Within the first 12 h, both indices performed with the highest AUROC at 10 h as follows: 0.723 (95% CI 0.605-0.840) and 0.739 (95% CI 0.626-0.853) for the ROX and ROX-HR index respectively. A ROX-HR index of > 6.80 was significantly associated with a lower risk of HFNC failure (hazard ratio 0.301 (95% CI 0.143-0.663)) at 10 h. This association was also observed at 2, 6, 18, and 24h, even with correction for potential confounding factors. For HFNC initiated post-extubation, only the ROX-HR index remained significantly associated with HFNC failure at all recorded time points between 1 and 24 h. A ROX-HR > 8.00 at 10 h was significantly associated with a lower risk of HFNC failure (hazard ratio 0.176 (95% CI 0.051-0.604)). CONCLUSION: While validation studies are required, the ROX-HR index appears to be a promising tool for early identification of treatment failure in patients initiated on HFNC for acute hypoxemic respiratory failure or as a preventative treatment after a planned extubation.

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.

Ministry of Health Clinical Practice Guidelines: Chronic Obstructive Pulmonary Disease.

The Ministry of Health (MOH) has updated the Clinical Practice Guidelines on Chronic Obstructive Pulmonary Disease (COPD) to provide doctors and patients in Singapore with evidence-based treatment for COPD. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH Clinical Practice Guidelines on COPD, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: https://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.