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.

Characterisation of the post-tuberculous phenotype of bronchiectasis: A real-world observational study.

OBJECTIVE: Bronchiectasis is a heterogeneous disease with distinct phenotypes. The post-tuberculosis (post-TB) bronchiectasis phenotype is prevalent in many countries but is under-studied. Our aim was to identify distinct phenotypic characteristics of post-TB bronchiectasis. METHODS: We recruited adults admitted between Jan 2010-Oct 2017 at Changi General Hospital, Singapore for bronchiectasis exacerbation. We collected demographics, symptoms, lung function, microbiology and FACED scores. Participants were followed-up until the next hospitalized exacerbation or end of study, whichever was sooner. Participants diagnosed by their attending respiratory specialist to have post-TB bronchiectasis were compared to those with bronchiectasis from other aetiologies. RESULTS: 148 participants were included with mean±standard deviation age 63 ± 9 years; 46 (31.1%) had post-TB bronchiectasis and 102 (68.9%) other aetiologies. Compared to other aetiologies, participants with post-TB bronchiectasis had significantly lower body mass index (BMI), more frequent presentation with haemoptysis, lower forced expiratory volume in one second (FEV1), more frequent isolation of nontuberculous mycobacteria (NTM), and higher FACED scores indicating greater disease severity. Over a median follow-up of 21 months, post-TB bronchiectasis was associated with shorter time to next hospitalized exacerbation (49 vs 76 months, Log-Rank p = .01). CONCLUSION: Post-TB bronchiectasis is a distinct entity with higher rates of haemoptysis and NTM isolation, more frequent exacerbations, and greater disease severity.

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.

Is bronchial thermoplasty cost-effective as treatment for problematic asthma patients? Singapore's perspective on a global model.

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.

A role for VAX2 in correct retinal function revealed by a novel genomic deletion at 2p13.3 causing distal Renal Tubular Acidosis: case report.

BACKGROUND: Distal Renal Tubular Acidosis is a disorder of acid-base regulation caused by functional failure of α-intercalated cells in the distal nephron. The recessive form of the disease (which is usually associated with sensorineural deafness) is attributable to mutations in ATP6V1B1 or ATP6V0A4, which encode the tissue-restricted B1 and a4 subunits of the renal apical H(+)-ATPase. ATP6V1B1 lies adjacent to the gene encoding the homeobox domain protein VAX2, at 2p13.3. To date, no human phenotype has been associated with VAX2 mutations. CASE PRESENTATION: The male Caucasian proband, born of a first cousin marriage, presented at 2 months with failure to thrive, vomiting and poor urine output. No anatomical problems were identified, but investigation revealed hyperchloremic metabolic acidosis with inappropriately alkaline urine and bilateral nephrocalcinosis. Distal Renal Tubular Acidosis was diagnosed and audiometry confirmed hearing loss at 2 years. ATP6V0A4 was excluded from genetic causation by intragenic SNP linkage analysis, but ATP6V1B1 completely failed to PCR-amplify in the patient, suggesting a genomic deletion. Successful amplification of DNA flanking ATP6V1B1 facilitated systematic chromosome walking to ascertain that the proband harbored a homozygous deletion at 2p13.3 encompassing all of ATP6V1B1 and part of VAX2; gene dosage was halved in the parents. This results in the complete deletion of ATP6V1B1 and disruption of the VAX2 open reading frame. Later ocular examinations revealed bilateral rod / cone photoreceptor dystrophy and mild optic atrophy. Similar changes were not detected in an adult harbouring a disruptive mutation in ATP6V1B1. CONCLUSIONS: The genomic deletion reported here is firstly, the only reported example of a whole gene deletion to underlie Distal Renal Tubular Acidosis, where the clinical phenotype is indistinguishable from that of other patients with ATP6V1B1 mutations; secondly, this is the first reported example of a human VAX2 mutation and associated ocular phenotype, supporting speculation in the literature that VAX2 is important for correct retinal functioning.

Fixed airways obstruction among patients with severe asthma: findings from the Singapore General Hospital-Severe Asthma Phenotype Study.

BACKGROUND: A subset of severe asthma patients has fixed airways obstruction, which is characterized by incomplete reversibility to bronchodilator challenge. We aimed to elucidate the factors associated with fixed airways obstruction in a cohort of patients with severe asthma in Singapore. METHODS: 245 patients from the Singapore General Hospital-Severe Asthma Phenotype Study (SGH-SAPS) were screened. These patients fulfilled World Health Organization criteria for "treatment-resistant severe asthma" and were all on combination of high-dose inhaled corticosteroids and long-acting beta2 agonists. 76 patients had pre- and postbronchodilator lung function tests and were selected for analysis. They were divided into two groups based on postbronchodilator (Post BD) forced expiratory volume in one second, PostBDFEV1 % predicted: ≥70% (Non-Fixed Obs) and < 70% (Fixed Obs). We compared clinical and demographic parameters between the two groups. RESULTS: Patients in the Fixed Obs group were more frequently past or current smokers and had a higher pack-year smoking history. Overall, pack-year smoking history had a modest negative correlation with PostBDFEV1 % predicted. Atopy, allergen sensitization (type and numbers), comorbidities, symptoms, health care utilization and medication use did not differ between the two groups. The prebronchodilator FEV1 % predicted, FEV1/FVC and FVC % predicted were significantly lower in the Fixed Obs group. In addition, prebronchodilator FVC % predicted accounted for more variability than FEV1/FVC in predicting PostBDFEV1% predicted. CONCLUSION: Smoking is associated with fixed airways obstruction in patients with treatment-resistant severe asthma in Singapore. Furthermore, our results suggest that both small and large airways obstruction contribute independently to fixed airways obstruction in severe asthma.

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

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

A review of psychological dysfunction in asthma: affective, behavioral and cognitive factors.

BACKGROUND: The research on psychological dysfunction in asthma is extensive but heterogeneous. We undertook a narrative review about the effects of psychological dysfunction on asthma. METHODS: Electronic searches of MEDLINE, EMBASE, CINAHL and the Cochrane Library were conducted, supplemented by hand-searching bibliographies and seeking expert opinion. RESULTS: The impact of psychological factors on asthma can be classified according to dysfunction in the domains of affect, behavior and cognition. Affective or emotional disturbance may lead to poor asthma control by directly modulating disease activity. Maladaptive behaviors may occur in asthma patients. These include maladaptive breathing behaviors, such as impaired voluntary drive to breathe and dysfunctional breathing, as well as impaired asthma health behaviors, that is, a coordinated range of activities performed to maintain good disease control. Dysfunctional cognitions (thoughts and beliefs) about asthma and impaired cognitive processing of the perception of dyspnea are associated with poorly controlled disease and asthma deaths, respectively. The three domains of psychological dysfunction are often closely intertwined, leading to vicious circles. CONCLUSIONS: We have conceptualized psychological dysfunction in asthma using a framework consisting of affect, behavior and cognition. Their influences are intertwined and complex. Future research should focus on the formulation of a psychological assessment tool based on this framework and evaluating its efficacy in improving asthma outcomes.

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

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

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

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

A lung mass: Not the usual suspect, but not above suspicion.

Lipoid pneumonia is an entity that is not commonly thought of when faced with opacities on the chest radiograph. The radiological changes of lipoid pneumonia can mimic pneumonia or malignancy. Due to this mimicry, it is commonly missed and alternative diagnoses should always be considered and ruled out when suspecting lipoid pneumonia. Although majority of lipoid pneumonias occur due to exogenous ingestion of oil, endogenous factors such as bronchial obstruction and pulmonary alveolar proteinosis can also result in this condition. The emphasis of this case is on the approach to and treatment of lipoid pneumonia, including its association with malignancy.

Evaluation of multi-component interventions for prevention of nosocomial pneumonia in older adults: a randomized, controlled trial.

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.

Asthma, Sinonasal Disease, and the Risk of Active Tuberculosis.

BACKGROUND: Although asthma is associated with impaired lung immunity, it is unclear whether asthma affects the risk of active tuberculosis (TB). Because the upper and lower airways are immunologically related, sinonasal disease may also modify susceptibility to TB disease. OBJECTIVES: To evaluate whether asthma and sinonasal disease prospectively modulate the risk of active TB in the Singapore Chinese Health Study. METHODS: In this population-based prospective cohort, we recruited 63,257 Chinese adults aged 45 to 74 years from 1993 to 1998 in Singapore, and conducted follow-up I interviews among 52,325 surviving participants from 1999 to 2004. Data on self-reported history of physician-diagnosed sinonasal disease were collected at baseline, and data on asthma and chronic bronchitis were collected at follow-up I interviews. Active TB cases were identified by linkage with the National TB Notification Registry through December 2014. Multivariable Cox proportional hazards regression models were used to estimate the risk of active TB. RESULTS: During a mean follow-up of 17 years from recruitment, there were 1249 cases of active TB, and among them, 678 cases were diagnosed in the 12-year period from follow-up I interviews. We observed reduced risk of active TB in those with a history of asthma at follow-up I (hazard ratio [HR], 0.55; 95% CI, 0.32-0.93) or sinonasal disease at baseline (HR, 0.59; 95% CI, 0.36-0.95). Conversely, history of chronic bronchitis was not associated with risk of TB (HR, 0.95; 95% CI, 0.68-1.31). CONCLUSIONS: Asthma or sinonasal disease may modulate immunological response to reduce the incidence of active TB in the adult population.

Asthma phenotypes in a multi-ethnic Asian cohort.

BACKGROUND: Identification of asthma phenotypes facilitates our understanding of asthma pathobiologies. Phenotypes observed in homogenous Asian cohorts have distinct differences from those described in Caucasian cohorts, suggesting that ethnicity may influence phenotypic expression. Phenotypic clusters in a multi-ethnic Southeast Asian cohort have not been described before, and direct comparisons of these clusters within a single study may reveal how ethnicity affects phenotypic expression. METHODS: Six hundred and thirty adult asthma patients from two healthcare institutions in Singapore were randomly assigned in a 2:1 fashion to a test and validation cohort. Latent class analysis was performed on both cohorts using age of asthma onset, sex, ethnicity, smoking status, body mass index, lung function, blood eosinophil count, asthma control test score, and exacerbation frequency as input variables. Phenotypic clusters between the test and validation cohorts were compared RESULTS: Three clusters were identified in both the test and validation cohorts, with corresponding clusters of each cohort sharing similar characteristics. Ethnic representation and asthma control were significantly different between clusters. Cluster one comprised Chinese females with late-onset asthma and the best asthma control. Cluster two comprised non-Chinese females with obesity and the worst asthma control. Cluster three was multi-ethnic with the greatest proportion of atopic patients. CONCLUSION: We identified three phenotypic clusters in our multi-ethnic Southeast Asian population, with distinct differences in ethnicity which may be attributable to inherent differences in baseline characteristics among ethnic groups.

A clinical prediction model for hospitalized COPD exacerbations based on "treatable traits".

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.

Predictive value of respiratory symptoms for the diagnosis of pollen-induced seasonal asthma among children and adults in Inner Mongolia.

BACKGROUND: The diagnosis of asthma is made on the basis of variable respiratory symptoms and supported by objective evidence of variable airflow limitation. However, spirometry and bronchoprovocation tests may not be routinely available in resource-scarce settings or in the context of large-scale epidemiological studies. There is a gap in knowledge about the predictive value of respiratory symptoms for the diagnosis of pollen-induced asthma. OBJECTIVE: The aim of this study was to investigate the predictive value of self-reported respiratory symptoms for diagnosing pollen-induced asthma. PATIENTS AND METHODS: We recruited 1,161 patients with respiratory symptoms who presented to the respiratory medicine outpatient clinic of two central hospitals in Inner Mongolia during the pollen season of July-September 2015. All patients were interviewed by a respiratory physician and completed a questionnaire survey, lung function tests and skin prick tests for common inhaled allergens. RESULTS: A total of 392 patients (33.8%) were diagnosed with asthma and 292 (25.2%, 160 adults, 132 children) with pollen-induced asthma. Respiratory symptoms of cough, wheezing, dyspnea, chest pain and nocturnal awakenings due to breathlessness were all associated with increased odds of being diagnosed with pollen-induced asthma, with cough being the most common symptom in both adults and children, giving a sensitivity of 90.6% in adults and 88.6% in children. Wheezing was the most specific symptom (78% and 89.5% in adults and children, respectively) compared to other symptoms. Overall, the positive predictive value of respiratory symptoms was poor for diagnosing pollen-induced asthma, with the exception of wheezing in children which had a high positive predictive value of 72.7%. CONCLUSION: Cough was the predominant symptom in adults and children with pollen-induced asthma. Wheezing was a reliable predictor of pollen-induced asthma in children. In adults, respiratory symptoms were not sufficiently reliable for diagnosing pollen-induced asthma.

The emergence of Aspergillus species in chronic respiratory disease.

Chronic lung disease is recognized as an important risk factor for developing pulmonary aspergillosis. The development of specific aspergillus-associated syndromes depends on host immunity and underlying lung disease. In the setting of asthma, hypersensitivity to Aspergillus can lead to allergic bronchopulmonary aspergillosis (ABPA) or severe asthma with fungal sensitization (SAFS). Chronic use of systemic or inhaled corticosteroids coupled with recurrent antibiotic use for exacerbations prevalent in chronic obstructive pulmonary disease (COPD) predisposes to chronic pulmonary aspergillosis (CPA). Prior pulmonary tuberculosis is a risk factor for CPA, a syndrome with a wide range of presentations including a simple aspergilloma, chronic cavities, necrosis or fibrosis. Accumulating evidence suggests that the presence of or colonization by Aspergillus in the setting of chronic lung disease can worsen clinical course and outcomes even in the absence of overt pulmonary aspergillosis. We propose that understanding the complex interplay between host and fungi may provide key insights into the pathogenesis of Aspergillus-associated pulmonary syndromes in the setting of chronic lung disease, and provide novel therapeutic approaches to improve its identification and management.