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Anthony CA Yii,1 CH Loh,1 PY Tiew,2,3 Huiying Xu,4 Aza AM Taha,1 Jansen Koh,1 Jessica Tan,5 Therese S Lapperre,6,7 Antonio Anzueto,8 Augustine KH Tee1 1Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore; 2Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore; 3Translational Respiratory Research Laboratory, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 4Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore; 5Department of General Medicine, Sengkang General Hospital, Singapore; 6Department of Respiratory Medicine, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; 7Duke-National University of Singapore Medical School, Singapore; 8Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, UT Health Science Center, San Antonio, TX, USA 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. Keywords: exacerbations, clinical prediction model, risk assessment

Ken Junyang Goh,1 Anthony Chau Ang Yii,1,2 Therese Sophie Lapperre,1,2 Adrian KW Chan,1–3 Fook Tim Chew,4 Sanjay H Chotirmall,5,* Mariko Siyue Koh1–3,* 1Department of Respiratory and Critical Care Medicine, Singapore General Hospital, 2Duke-National University of Singapore Medical School, 3Allergy Centre, Singapore General Hospital, 4Department of Biological Sciences, Faculty of Science, National University of Singapore, 5Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore *These authors contributed equally to this work Background: Severe asthma is a largely heterogeneous disease with varying phenotypic profiles. The relationship between specific allergen sensitization and asthma severity, particularly in Asia, remains unclear. We aim to study the prevalence of specific allergen sensitization patterns and investigate their association with outcomes in a severe asthma cohort in an Asian setting. Methods: We conducted a cross-sectional study of patients receiving step 4 or 5 Global Initiative for Asthma treatment. Univariate and multivariate analyses were performed to assess the association between sensitization to a specific identifiable allergen by skin prick test (SPT) and uncontrolled asthma (defined in our study as the use of ≥2 steroid bursts or hospitalization in the past year, a history of near-fatal asthma or evidence of airflow obstruction on spirometry). Results: Two hundred and six severe asthma patients (mean age 45±17 years, 99 [48.1%] male) were evaluated. Of them, 78.2% had a positive SPT to one or more allergens. The most common allergen to which patients were sensitized was house dust mites (Blomia tropicalis, Dermatophagoides pteronyssinus and Dermatophagoides farinae). Also, 11.7% were sensitized to Aspergillus species. On multivariate analysis, Aspergillus sensitization was associated with uncontrolled asthma (odds ratio 6.07, 95% confidence interval 1.80–20.51). In particular, Aspergillus sensitization was independently associated with the use of ≥2 steroid bursts in the past year (odds ratio 3.05, 95% confidence interval 1.04–8.95). No similar associations of uncontrolled asthma with sensitization to any other allergens were found. Conclusion: High allergen, specifically Aspergillus sensitization was observed in the Asian population with severe asthma by SPT. Aspergillus sensitization was specifically associated with frequent exacerbations and a greater corticosteroid requirement. An improved understanding of the severe asthma with Aspergillus sensitization phenotype is warranted, which is likely a subgroup of severe asthma with fungal sensitization. Keywords: atopy, airway, fungus, Aspergillus, outcomes, prognosis

Aims: To evaluate the efficacy of multi-component interventions for prevention of hospital-acquired pneumonia in older patients hospitalized in geriatric wards., Methods: A randomized, parallel-group, controlled trial was undertaken in patients aged 65 and above who were admitted to a tertiary hospital geriatric unit from January 1, 2016 to June 30, 2018 for an acute non-respiratory illness. Participants were randomized by to receive either a multi-component intervention (consisting of reverse Trendelenburg position, dysphagia screening, oral care and vaccinations), or usual care. The outcome measures were the proportion of patients who developed hospital-acquired pneumonia during hospitalisation, and mean time from randomization to the next hospitalisation due to respiratory infections in 1 year., Results: A total of 123 participants (median age, 85; 43.1% male) were randomized, (n = 59) to intervention group and (n = 64) to control group. The multi-component interventions did not significantly reduce the incidence of hospital-acquired pneumonia but did increase the mean time to next hospitalisation due to respiratory infection (11.5 months vs. 9.5 months; P = 0.049), and reduced the risk of hospitalisation in 1 year (18.6% vs. 34.4%; P = 0.049). Implementation of multi-component interventions increased diagnoses of oropharyngeal dysphagia (35.6% vs. 20.3%; P < 0.001) and improved the influenza (54.5% vs 17.2%; P < 0.001) and pneumococcal vaccination rates (52.5% vs. 20.3%; P < 0.001)., Conclusions: The nosocomial pneumonia multi-component intervention did not significantly reduce the incidence of hospital-acquired pneumonia during hospitalisation but reduce subsequent hospitalisations for respiratory infections., Clinical Trial Registration: ClinicalTrial.gov, NCT04347395., (© 2021. European Geriatric Medicine Society.)

Background: An elevated blood eosinophil count when asthma is stable predicts exacerbations and therapeutic response to corticosteroids or biologics targeting eosinophils. Few studies have examined the prognostic value of blood eosinophils measured at exacerbation., Aim: To elucidate the relationship between a spot blood eosinophil count-measured at the onset of a life-threatening asthma exacerbation-with indices of exacerbation severity and risk of subsequent exacerbations., Methods: Real-world, retrospective review of all life-threatening asthma cases admitted at 4 public hospitals in Singapore between 2011-2015. We assessed the trends and correlations between blood eosinophil count on admission with arterial blood gas values, duration of mechanical ventilation, and risk of death, hypoxic ischemic encephalopathy or respiratory arrest. Risk of future exacerbations among survivors was modelled using Cox regression and survival curves., Results: There were 376 index life-threatening exacerbations with median blood eosinophil count (5-95th percentiles) of 0.270 × 10 9 /L (0-1.410 × 10 9 /L). Arterial pH decreased and PCO 2 increased with increasing eosinophil count. Duration of mechanical ventilation and risk of death, hypoxic ischaemic encephalopathy or respiratory arrest did not vary with eosinophils. Among 329 survivors who were followed-up over a median of 52 months, blood eosinophils ≥1.200 × 10 9 /L was associated with an increased hazard of emergency visits and/or admissions for asthma (hazard ratio 1.8, 95% confidence interval 1.1-2.9, P = .02)., Conclusion: In this study of life-threatening asthma, we found that a spot blood eosinophil count correlates with severity of respiratory failure and predicts risk of subsequent exacerbations., (© 2019 John Wiley & Sons Ltd.)

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., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Assessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short- but not long-term risk. Problematic asthma patients with unfavorable long-term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment., Aim: To identify distinct trajectories of severe exacerbation rates among "problematic asthma" patients and develop a risk score to predict the most unfavorable trajectory., Methods: Severe exacerbation rates over five years for 177 "problematic asthma" patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group-based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory., Results: Three distinct trajectories were found: 58.5% had rare intermittent severe exacerbations ("infrequent"), 32.0% had frequent severe exacerbations at baseline but improved subsequently ("nonpersistently frequent"), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near-fatal asthma ("persistently frequent"). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near-fatal asthma (+1 point), body mass index ≥25kg/m 2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point), and depression (+1 point) was predictive of the "persistently frequent" trajectory (area under the receiver operating characteristic curve: 0.84, sensitivity 72.2%, specificity 81.1% using cutoff ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort., Conclusions: Patients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently frequent severe exacerbations in the future., (© 2017 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Background and Objective: Bronchial thermoplasty (BT) has been shown to be effective at reducing asthma exacerbations and improving asthma control for patients with severe persistent asthma but it is also expensive. Evidence on its cost-effectiveness is limited and inconclusive. In this study, we aim to evaluate the incremental cost-effectiveness of BT combined with optimized asthma therapy (BT-OAT) relative to OAT for difficult-to-treat and severe asthma patients in Singapore, and to provide a general framework for determining BT's cost-effectiveness in other healthcare settings., Methods: We developed a Markov model to estimate the costs and quality-adjusted life years (QALYs) gained with BT-OAT versus OAT from the societal and health system perspectives. The model was populated using Singapore-specific costs and transition probabilities and utilities from the literature. Sensitivity analyses were conducted to identify the main factors determining cost-effectiveness of BT-OAT., Results: BT-OAT is not cost-effective relative to OAT over a 5-year time horizon with an incremental cost-effectiveness ratio (ICER) of $US138 889 per QALY from the societal perspective and $US139 041 per QALY from the health system perspective. The cost-effectiveness of BT-OAT largely depends on a combination of the cost of the BT procedure and the cost of asthma-related hospitalizations and emergency department (ED) visits., Conclusion: Based on established thresholds for cost-effectiveness, BT-OAT is not cost-effective compared with OAT in Singapore. Given its current clinical efficacy, BT-OAT is most likely to be cost-effective in a setting where the cost of BT procedure is low and costs of hospitalization and ED visits are high., (© 2017 Asian Pacific Society of Respirology.)