Trait profiles in difficult-to-treat asthma: Clinical impact and response to systematic assessment.

BACKGROUND: Multidisciplinary systematic assessment improves outcomes in difficult-to-treat asthma, but without clear response predictors. Using a treatable-traits framework, we stratified patients by trait profile, examining clinical impact and treatment responsiveness to systematic assessment. METHODS: We performed latent class analysis using 12 traits on difficult-to-treat asthma patients undergoing systematic assessment at our institution. We examined Asthma Control Questionnaire (ACQ-6) and Asthma Quality of Life Questionnaire (AQLQ) scores, FEV1 , exacerbation frequency, and maintenance oral corticosteroid (mOCS) dose, at baseline and following systematic assessment. RESULTS: Among 241 patients, two airway-centric profiles were characterized by early-onset with allergic rhinitis (n = 46) and adult onset with eosinophilia/chronic rhinosinusitis (n = 60), respectively, with minimal comorbid or psychosocial traits; three non-airway-centric profiles exhibited either comorbid (obesity, vocal cord dysfunction, dysfunctional breathing) dominance (n = 51), psychosocial (anxiety, depression, smoking, unemployment) dominance (n = 72), or multi-domain impairment (n = 12). Compared to airway-centric profiles, non-airway-centric profiles had worse baseline ACQ-6 (2.7 vs. 2.2, p < .001) and AQLQ (3.8 vs. 4.5, p < .001) scores. Following systematic assessment, the cohort showed overall improvements across all outcomes. However, airway-centric profiles had more FEV1 improvement (5.6% vs. 2.2% predicted, p < .05) while non-airway-centric profiles trended to greater exacerbation reduction (1.7 vs. 1.0, p = .07); mOCS dose reduction was similar (3.1 mg vs. 3.5 mg, p = .782). CONCLUSION: Distinct trait profiles in difficult-to-treat asthma are associated with different clinical outcomes and treatment responsiveness to systematic assessment. These findings yield clinical and mechanistic insights into difficult-to-treat asthma, offer a conceptual framework to address disease heterogeneity, and highlight areas responsive to targeted intervention.

Interval change in fractional exhaled nitric oxide (FENO) reflects short-term change in adherence following electronic inhaler reminders.

BACKGROUND: In asthma, suppression of fractional exhaled nitric oxide (FENO) is a marker of adherence in the short-term. The usefulness of FENO to indicate change in adherence in the longer term is unknown. The aims of this study were to determine the relationship between changes in adherence and corresponding changes in FENO over short (1 week) and long-term (3 month) periods. METHODS: After establishing initial ICS adherence using electronic inhaler monitor (EIM) devices, reminders were switched on for 1 week ('short-term') to optimize adherence. Reminders were then switched off and patients followed up after 3 months ('long-term'). FENO was measured at the start and end of each period. Using linear regression, we analyzed change in FENO in relation to change in adherence. RESULTS: Forty-two patients contributed complete data for analysis. In the short-term, change in adherence was independently associated with change in FENO (ß = -0.36, p = 0.036) even after adjusting for initial adherence and ICS dose. The higher the initial FENO, the greater the decline in FENO with improved adherence. This relationship between change in adherence and change in FENO was not observed in the long-term. CONCLUSION: Change in adherence over 1 week following the use of EIM reminders independently predicted change in FENO. This relationship was not maintained at 3 months.

Nebulizer versus metered dose inhaler with space chamber (MDI spacer) for acute asthma and chronic obstructive pulmonary disease exacerbation: attitudes of patients and healthcare providers in the COVID-19 era.

OBJECTIVE: Short-acting bronchodilators for asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly delivered by nebulizers although administration using metered dose inhaler with space chamber (MDI spacer) has been shown to be equally efficacious. There are few studies examining patients' and healthcare providers' attitudes on the two administration methods in adults. This study explores patients' and healthcare providers' attitudes on the use of nebulizer versus MDI spacer for acute asthma and COPD exacerbations in adults. METHODS: Patients admitted for asthma or COPD exacerbations, doctors, and nurses in a university-affiliated hospital were surveyed from 1 April 2021 to 30 September 2021 regarding their views on the effectiveness, ease of use, preparation and administration, side effects, and infection risk of the two administration methods. RESULTS: Ninety-nine patients, 103 doctors, and 650 nurses completed the survey. 60.6% of patients perceived nebulizer to be more effective. Patients who found nebulizer more comfortable were more likely to prefer nebulizer (OR 43.97, p = 0.01), while those who associated it with a greater infection risk were less likely to prefer nebulizer (OR 0.15, p = 0.03). 49.5% of doctors and 49.1% of nurses perceived nebulizer to be more effective, compared to 10.7% and 34.5%, respectively, for MDI spacer. Effectiveness and patient comfort influenced doctors' and nurses' preference for nebulizer while ease of preparation and administration influenced nurses' preference only. CONCLUSIONS: Patients and healthcare providers perceived nebulizer to be more effective. Factors unique to each group influenced their preference for nebulizer.

Assessing the cost-effectiveness of mepolizumab as add-on therapy to standard of care for severe eosinophilic asthma in Singapore.

OBJECTIVE: To evaluate the cost-effectiveness of mepolizumab added to standard of care (SOC) compared with SOC alone among patients with severe uncontrolled eosinophilic asthma in the Singapore setting. METHODS: A Markov model with three health states (asthma on mepolizumab and SOC, asthma on SOC alone, and death) was developed from a healthcare system perspective over a lifetime horizon. During each 4-week cycle, patients in the non-death health states could experience asthma exacerbations requiring oral corticosteroid burst, emergency department visit, or hospitalization. Asthma-related mortality following an exacerbation or all-cause mortality could also occur at each cycle. The model was populated using local costs while utilities were derived from international literature. Transition probabilities were obtained from a mixture of Singapore-specific and internationally published data. RESULTS: The base-case analysis comparing mepolizumab plus SOC with SOC alone resulted in an incremental cost-effectiveness ratio (ICER) of SGD335 486 (USD238 195) per quality-adjusted life-year (QALY) gained. Sensitivity analysis demonstrated that the ICER was most sensitive to the price of mepolizumab, followed by the proportion of exacerbations which required hospital intensive care. Despite restricting mepolizumab use to patients with a higher baseline exacerbation rate (3 in the past year) in a scenario analysis, the ICER remained high at SGD238 876 (USD 169 602) per QALY gained. CONCLUSION: At its current price, mepolizumab is not considered a cost-effective use of healthcare resources in Singapore. Substantial price reductions for mepolizumab are required to improve its cost-effectiveness to an acceptable range. These results will be useful to inform national funding decisions.

Laryngeal hypersensitivity and abnormal cough response during mannitol bronchoprovocation challenge.

BACKGROUND AND OBJECTIVE: Inhalational challenge with dry mannitol powder may potentially induce cough by two mechanisms: airway bronchoconstriction or laryngeal irritation. This prospective observational study investigated laryngeal and bronchial components of cough induced by mannitol challenge. METHODS: We recruited consecutive patients referred for clinical mannitol challenge. The Newcastle Laryngeal Hypersensitivity Questionnaire (LHQ) was administered. Throughout testing, coughs were audio-recorded to derive a cough frequency index per time and dose of mannitol. Relationships between cough indices, laryngeal hypersensitivity and bronchial hyperresponsiveness (BHR) were examined. Participants were classified by cough characteristics with k-means cluster analysis. RESULTS: Of 90 patients who underwent challenge, 83 completed both the questionnaire and challenge. Cough frequency was greater in patients with abnormal laryngeal hypersensitivity (p = 0.042), but not in those with BHR. There was a moderate negative correlation between coughs per minute and laryngeal hypersensitivity score (r = -0.315, p = 0.004), with lower LHQ scores being abnormal. Cluster analysis identified an older, female-predominant cluster with higher cough frequency and laryngeal hypersensitivity, and a younger, gender-balanced cluster with lower cough frequency and normal laryngeal sensitivity. CONCLUSION: Cough frequency during mannitol challenge in our cohort reflected laryngeal hypersensitivity rather than BHR. Laryngeal hypersensitivity was more often present among older female patients. With the incorporation of cough indices, mannitol challenge may be useful to test for laryngeal hypersensitivity as well as BHR.

Blood eosinophil count correlates with severity of respiratory failure in life-threatening asthma and predicts risk of subsequent exacerbations.

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 × 109 /L (0-1.410 × 109 /L). Arterial pH decreased and PCO2 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 × 109 /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.

Predictors of future exacerbations in a multi-ethnic Asian population with asthma.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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, p < 0.001) were independent predictors of future exacerbations. CONCLUSIONS: 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.

Nonadherence in the era of severe asthma biologics and thermoplasty.

Nonadherence to inhaled preventers impairs asthma control. Electronic monitoring devices (EMDs) can objectively measure adherence. Their use has not been reported in difficult asthma patients potentially suitable for novel therapies, i.e. biologics and bronchial thermoplasty.Consecutive patients with difficult asthma were assessed for eligibility for novel therapies. Medication adherence, defined as taking >75% of prescribed doses, was assessed by EMD and compared with standardised clinician assessment over an 8-week period.Among 69 difficult asthma patients, adherence could not be analysed in 13, due to device incompatibility or malfunction. Nonadherence was confirmed in 20 out of 45 (44.4%) patients. Clinical assessment of nonadherence was insensitive (physician 15%, nurse 28%). Serum eosinophils were higher in nonadherent patients. Including 11 patients with possible nonadherence (device refused or not returned) increased the nonadherence rate to 31 out of 56 (55%) patients. Severe asthma criteria were fulfilled by 59 out of 69 patients. 47 were eligible for novel therapies, with confirmed nonadherence in 16 out of 32 (50%) patients with EMD data; including seven patients with possible nonadherence increased the nonadherence rate to 23 out of 39 (59%).At least half the patients eligible for novel therapies were nonadherent to preventers. Nonadherence was often undetectable by clinical assessments. Preventer adherence must be confirmed objectively before employing novel severe asthma therapies.

Diagnosis of concomitant inducible laryngeal obstruction and asthma.

BACKGROUND: Inducible laryngeal obstruction, an induced, inappropriate narrowing of the larynx, leading to symptomatic upper airway obstruction, can coexist with asthma. Accurate classification has been challenging because of overlapping symptoms and the absence of sensitive diagnostic criteria for either condition. OBJECTIVE: To evaluate patients with concomitant clinical suspicion for inducible laryngeal obstruction and asthma. We used a multidisciplinary protocol incorporating objective diagnostic criteria to determine whether asthma, inducible laryngeal obstruction, both, or neither diagnosis was present. METHODS: Consecutive patients were prospectively assessed by a laryngologist, speech pathologist and respiratory physician. Inducible laryngeal obstruction was diagnosed by visualizing paradoxical vocal fold motion either at baseline or following mannitol provocation. Asthma was diagnosed by physician assessment with objective variable airflow obstruction. Validated questionnaires for laryngeal dysfunction and relevant comorbidities were administered. RESULTS: Of 69 patients, 15 had asthma alone, 11 had inducible laryngeal obstruction alone and 14 had neither objectively demonstrated. Twenty-nine patients had both diagnoses. In 19 patients, inducible laryngeal obstruction was only seen following provocation. Among patients with inducible laryngeal obstruction, chest tightness was more frequent with concurrent asthma. Among patients with asthma, stridor was more frequent with concurrent inducible laryngeal obstruction. Cough was more frequently found in asthma alone, whereas difficulty with inspiration and symptoms triggered by psychological stress were more frequently found in inducible laryngeal obstruction alone. Patients with asthma alone had greater airflow obstruction. Relevant comorbidities were frequent (rhinitis in 85%, gastro-oesophageal reflux in 65%), and questionnaire scores for laryngeal dysfunction were abnormal. However, neither comorbidities nor questionnaires differentiated patients with or without inducible laryngeal obstruction. CONCLUSIONS AND CLINICAL RELEVANCE: In this cohort with suspected inducible laryngeal obstruction and asthma, 42% had objective evidence of both conditions. Clinical assessment, questionnaire scores and comorbidity burden were not sufficiently discriminatory for diagnosis, highlighting the necessity of objective diagnostic testing.

Recent developments and highlights in biomarkers in allergic diseases and asthma.

The potential of precision medicine in allergy and asthma has only started to be explored. A significant clarification in the pathophysiology of rhinitis, chronic rhinosinusitis, asthma, food allergy and drug hypersensitivity was made in the last decade. This improved understanding led to a better classification of the distinct phenotypes and to the discovery of new drugs such as biologicals, targeting phenotype-specific mechanisms. Nevertheless, many conditions remain poorly understood such as non-eosinophilic airway diseases or non-IgE-mediated food allergy. Moreover, there is a need to predict the response to specific therapies and the outcome of drug and food provocations. The identification of patients at risk of progression towards severity is also an unmet need in order to establish adequate preventive or therapeutic measures. The implementation of precision medicine in the clinical practice requires the identification of phenotype-specific markers measurable in biological matrices. To become useful, these biomarkers need to be quantifiable by reliable systems, and in samples obtained in an easy, rapid and cost-efficient way. In the last years, significant research resources have been put in the identification of valid biomarkers for asthma and allergic diseases. This review summarizes these recent advances with focus on the biomarkers with higher clinical applicability.

Diagnosis of severe asthma.

Patients with asthma that is uncontrolled despite high intensity medication can present in both primary and specialist care. An increasing number of novel (and expensive) treatments are available for patients who fail conventional asthma therapy, but these may not be appropriate for all such patients. It is essential that a rigorous evaluation process be undertaken for these patients to identify those with biologically severe asthma who will require novel therapies, and those who may improve with control of contributory factors. In this article, we describe three key steps in the diagnostic evaluation process for severe asthma. The first step is confirmation of asthma diagnosis with objective evidence of variable airflow obstruction. The second involves management of contributory factors such as non-adherence, poor inhaler technique, ongoing asthma triggers, and comorbidities. The third step involves phenotyping and endotyping of patients with severe asthma. We provide a practical approach to implementing these measures in both primary and secondary care.

Validated questionnaires heighten detection of difficult asthma comorbidities.

OBJECTIVE: Multiple extra-pulmonary comorbidities contribute to difficult asthma, but their diagnosis can be challenging and time consuming. Previous data on comorbidity detection have focused on clinical assessment, which may miss certain conditions. We aimed to locate relevant validated screening questionnaires to identify extra-pulmonary comorbidities that contribute to difficult asthma, and evaluate their performance during a difficult asthma evaluation. METHODS: MEDLINE was searched to identify key extra-pulmonary comorbidities that contribute to difficult asthma. Screening questionnaires were chosen based on ease of use, presence of a cut-off score, and adequate validation to help systematically identify comorbidities. In a consecutive series of 86 patients referred for systematic evaluation of difficult asthma, questionnaires were administered prior to clinical consultation. RESULTS: Six difficult asthma comorbidities and corresponding screening questionnaires were found: sinonasal disease (allergic rhinitis and chronic rhinosinusitis), vocal cord dysfunction, dysfunctional breathing, obstructive sleep apnea, anxiety and depression, and gastro-oesophageal reflux disease. When the questionnaires were added to the referring clinician's impression, the detection of all six comorbidities was significantly enhanced. The average time for questionnaire administration was approximately 40 minutes. CONCLUSIONS: The use of validated screening questionnaires heightens detection of comorbidities in difficult asthma. The availability of data from a battery of questionnaires prior to consultation can save time and allow clinicians to systematically assess difficult asthma patients and to focus on areas of particular concern. Such an approach would ensure that all contributing comorbidities have been addressed before significant treatment escalation is considered.

Coexisting atopic conditions influence the likelihood of allergic bronchopulmonary aspergillosis in asthma.

BACKGROUND: The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in asthma is often made in patients with total serum IgE levels greater than 1,000 IU/mL in conjunction with evidence of Aspergillus sensitization. The specificity of total serum IgE for the diagnosis of ABPA is low even when combined with serum Aspergillus specific IgE. OBJECTIVE: To determine the prevalence of ABPA and to identify alternative clinical predictors for ABPA among asthmatic patients with a total serum IgE level greater than 1,000 IU/ml. METHODS: This study was conducted in a tertiary hospital in Melbourne, Australia, with a large asthma and allergy service. Patients with asthma and total serum IgE levels greater than 1,000 IU/ml from January 1, 2005, through December 31, 2014, were included. Patients were considered to have concomitant allergic conditions if they had atopic eczema, allergic rhinitis, or both. The diagnosis of ABPA was based on the managing physician's documented diagnosis and referenced to criteria proposed by the International Society for Human and Fungal Mycology. RESULTS: The prevalence of ABPA in our cohort was 15.8%. Older age, elevated total serum IgE level, reduced lung function, and the absence of other concomitant allergic conditions increased the risk of ABPA. After multivariate logistic regression, patients without concomitant allergic conditions had an odds ratio of 4.4 (95% confidence interval, 1.9-10.1; P = .001) for ABPA when compared with patients with allergic conditions. CONCLUSION: The absence of atopic eczema and allergic rhinitis in these patients increases the likelihood of ABPA. Eliciting an accurate allergy history may be a useful bedside clinical tool when considering the diagnosis of ABPA.

Comorbidities in difficult asthma are independent risk factors for frequent exacerbations, poor control and diminished quality of life.

BACKGROUND AND OBJECTIVE: Little is known about how comorbidities affect difficult asthma patients across different domains of asthma outcomes. We hypothesized that comorbidities in difficult asthma significantly influence asthma outcomes. METHODS: We analysed 90 consecutive patients who underwent systematic assessment at our hospital's difficult asthma clinic. Eight comorbidities were assessed in all patients. They were allergic rhinitis, chronic rhinosinusitis (CRS), gastroesophageal reflux disease, obesity, obstructive sleep apnoea, anxiety or depression, dysfunctional breathing (DB) and vocal cord dysfunction (VCD). Asthma outcomes examined were exacerbation frequency (≥3/year vs <3/year), asthma control using the Asthma Control Test (ACT) and quality of life using the Asthma Quality of Life Questionnaire (AQLQ). Multivariate logistic regression was performed for dichotomous outcomes and linear regression for continuous outcomes. Analyses were adjusted for lung function and absolute blood eosinophils. RESULTS: Increasing BMI was an independent risk factor for exacerbations (OR: 1.1, 95% CI: 1-1.1, P = 0.042), lower ACT score (ß coefficient: -0.25, 95% CI: -0.37 to -0.12, P < 0.001) and poorer AQLQ (ß coefficient: -0.05, 95% CI: -0.09 to -0.02, P = 0.006). DB predicted lower ACT (ß coefficient: -2.85, 95% CI: -5 to -0.7, P = 0.01) and AQLQ scores (ß coefficient: -0.73, 95% CI: -1.34 to -0.12, P = 0.02). Patients with CRS had more exacerbations (OR: 4, 95% CI: 1.5-10.9, P = 0.006). Patients with VCD had lower AQLQ scores (ß coefficient: -0.78, 95% CI: -1.38 to -0.18, P = 0.012). CONCLUSION: Comorbidities independently impact a broad spectrum of outcomes in difficult asthma. Systematic evaluation of these conditions is essential in difficult asthma.

Predictors of persistent poor control and validation of ASSESS score: Longitudinal 5-year follow-up of severe asthma cohort.

Background: Longitudinal predictors of persistent poor asthma control in severe asthma (SA) cohort remain scarce. The predictive value of the asthma severity scoring system (ASSESS) in the SA cohort outside the original study and in the Asian population is unknown. Objective: We sought to determine the 5-year longitudinal outcome of patients with SA and validate the use of ASSESS score in predicting future outcomes in SA. Methods: A prospective longitudinal observational study of patients with SA attending the multidisciplinary specialist SA clinic of the Singapore General Hospital from 2011 to 2021 was conducted. The number of exacerbations and asthma control test results were recorded yearly for 5 consecutive years. The ASSESS score was computed at baseline, and the area under the receiver-operating characteristic curve for predicting persistent poor asthma control was generated. Results: Of the 489 patients recruited into the study, 306 patients with 5-year follow-up data were analyzed. Seventy-three percent had type 2 inflammation with increased overall exacerbations over 5 years (rate ratio, 2.55; 95% CI, 1.31-4.96; P = .006) relative to non-type 2 SA. In the multivariate model, bronchiectasis, gastroesophageal reflux disease, and an asthma control test score of less than 20 were significantly associated with persistent poor asthma control over 5 years. ASSESS scores were good at predicting persistent poor asthma control with an area under the receiver-operating characteristic curve of 0.71 (95% CI, 0.57-0.84). Conclusions: Bronchiectasis and gastroesophageal reflux disease are predictors for persistent poor asthma control and targeted traits for precision medicine in SA. The ASSESS score has a good prediction for persistent poor asthma control over 5 years.

Factors affecting pleural fluid adenosine deaminase level and the implication on the diagnosis of tuberculous pleural effusion: a retrospective cohort study.

BACKGROUND: Adenosine deaminase (ADA) is useful in the diagnosis of tuberculous pleural effusion (TPE). This study aims to determine the factors affecting pleural fluid ADA levels and to establish the optimal ADA levels for diagnosis of TPE for different age groups. METHODS: This was a retrospective study from January 2007 to October 2011. One hundred and sixty patients who had pleural fluid ADA performed for investigation of pleural effusion were analyzed. Variables examined included demographics, pleural fluid characteristics and peripheral blood counts. The ADA cut-offs according to age were selected using the receiver operating characteristic (ROC) curve. RESULTS: The mean pleural fluid ADA was significantly higher in the TPE group (100 ± 35 IU/L) compared to non TPE patients (30 ± 37 IU/L). There was significant correlation between pleural fluid ADA and age, pleural fluid protein, LDH, and fluid absolute lymphocyte count. The strongest correlation was seen with age (r = -0.621). For patients ≤ 55 years old the ROC for ADA had area under curve (AUC) of 0.887. A pleural fluid ADA of 72 IU/L had sensitivity of 95.1%, specificity of 87.5%, positive predictive value (PPV) of 95.1% and negative predictive value (NPV) of 87.5% for the diagnosis of TPE. For patients > 55 years old the AUC is 0.959. ADA of 26 IU/L had a sensitivity of 94.7%, specificity of 80.4%, PPV of 62% and NPV of 97.8%. CONCLUSIONS: There is a significant negative correlation between pleural fluid ADA and age. For older patients, a lower ADA cut-off should be used to exclude TPE.

Electronic Inhaler Monitoring for Chronic Airway Disease: Development and Application of a Multidimensional Efficacy Framework.

Inhaled therapy is the cornerstone of chronic airway disease therapy, but poor adherence to controller inhalers worsens clinical outcomes and increases cost. Monitoring of controller use is needed to improve adherence, and monitoring of reliever use can predict impending exacerbations. Both can be accurately achieved by electronic inhaler monitoring (EIM). However, evidence for EIM use in clinical practice is limited and varied, and knowledge gaps remain across different outcomes and health settings. We aimed to develop a framework to assess EIM systematically across all aspects of efficacy, apply this framework to the current literature, and identify gaps in efficacy to inform future development in the field. We adapted an existing framework for diagnostic tests, consisting of six levels of efficacy with ascending clinical relevance: technical, diagnostic accuracy, diagnostic thinking, therapeutic, patient outcome, and societal efficacy. Tailoring this framework to EIM, we incorporated expert feedback and applied it to the EIM efficacy literature. We found that EIM has good diagnostic accuracy, diagnostic thinking, and therapeutic efficacies, but evidence is lacking for specific aspects of technical, patient outcome, and societal efficacies. Further development of EIM requires improved reliability, usability, and data security for patients, and optimal integration with electronic medical records and overall patient care. Defining appropriate target patient groups and pairing EIM data with effective interventions, in conjunction with reducing costs through technological innovation and economies of scale, will enhance patient and societal outcome efficacies.

Diagnostic and Therapeutic Outcomes Following Systematic Assessment of Patients with Concurrent Suspected Vocal Cord Dysfunction and Asthma.

BACKGROUND: Vocal cord dysfunction (VCD) is present in 25% to 50% of patients with asthma. When both diagnoses are suspected, accurate diagnosis and targeted management represent a clinical challenge. OBJECTIVE: To evaluate diagnostic and therapeutic outcomes following systematic assessment for patients with concurrent suspected VCD and asthma. METHODS: Patients underwent systematic evaluation by clinical assessment and validated questionnaires, followed by multidisciplinary management. VCD was confirmed by visualization of paradoxical vocal fold motion at baseline or following provocation. Asthma was confirmed by demonstrating variable airflow obstruction. Asthma medications were deescalated in those with low clinical probability of asthma and no variable airflow obstruction. Response to 2 or more sessions of speech pathology was assessed by subjective report and standardized questionnaires. RESULTS: Among 212 consecutive patients, 62 (29%) patients had both VCD and asthma, 54 (26%) had VCD alone, 51 (24%) had asthma alone, and 45 (21%) had neither. Clinician assessment and the Laryngeal Hypersensitivity Questionnaire both predicted laryngoscopy-confirmed VCD. Deescalation or discontinuation of asthma therapy was possible in 37 of 59 (63%) patients without variable airflow obstruction, and was most successful (odds ratio, 5.5) in the presence of laryngoscopy-confirmed VCD (25 of 31, or 81%) Patients with VCD responded subjectively to 2 or more sessions of speech pathology, but laryngeal questionnaire scores did not improve. CONCLUSIONS: Expert clinician assessment and the Laryngeal Hypersensitivity Questionnaire predict the presence of laryngoscopy-confirmed VCD. Systematic assessment for both VCD and asthma facilitates deescalation or discontinuation of unnecessary asthma medications. Subjective symptom improvement following speech pathology was not paralleled by laryngeal questionnaire scores in this cohort.

A risk prediction score to identify patients at low risk for COVID-19 infection.

Introduction: Singapore's enhanced surveillance programme for COVID-19 identifies and isolates hospitalised patients with acute respiratory symptoms to prevent nosocomial spread. We developed risk prediction models to identify patients with low risk for COVID-19 from this cohort of hospitalised patients with acute respiratory symptoms. Methods: This was a single-centre retrospective observational study. Patients admitted to our institution's respiratory surveillance wards from 10 February to 30 April 2020 contributed data for analysis. Prediction models for COVID-19 were derived from a training cohort using variables based on demographics, clinical symptoms, exposure risks and blood investigations fitted into logistic regression models. The derived prediction models were subsequently validated on a test cohort. Results: Of the 1,228 patients analysed, 52 (4.2%) were diagnosed with COVID-19. Two prediction models were derived, the first based on age, presence of sore throat, dormitory residence, blood haemoglobin level (Hb), and total white blood cell counts (TW), and the second based on presence of headache, contact with infective patients, Hb and TW. Both models had good diagnostic performance with areas under the receiver operating characteristic curve of 0.934 and 0.866, respectively. Risk score cut-offs of 0.6 for Model 1 and 0.2 for Model 2 had 100% sensitivity, allowing identification of patients with low risk for COVID-19. Limiting COVID-19 screening to only elevated-risk patients reduced the number of isolation days for surveillance patients by up to 41.7% and COVID-19 swab testing by up to 41.0%. Conclusion: Prediction models derived from our study were able to identify patients at low risk for COVID-19 and rationalise resource utilisation.