Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation 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.Ministry of Education (MOE)Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionSupported by the Singapore Ministry of Health’s National Medical Research Council under its Transition Award NMRC/TA/0048/2016 (S.H.C.) and Changi General Hospital Research grant CHF2016.03-P (T.B.L.). The work performed at NUS was supported by the Singapore Ministry of Education Academic Research Fund, SIgN, and National Medical Research Council grants N-154-000-038-001, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, SIgN-06-006, SIgN-08-020, and NMRC/1150/2008 (F.T.C.); J.D.C. is supported by the GSK/British Lung Foundation Chair of Respiratory Research

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

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 Clavispora. Aspergillus 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.MOE (Min. of Education, S’pore)NMRC (Natl Medical Research Council, S’pore)Published versio

<i>Neisseria</i> 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.Published versio

Pulmonary Function Test: Spirometry

Spirometry is a useful tool in assessing the physiological lung function of a patient, and can be helpful in differentiating the etiology of the patient's symptoms. Indications for the test and the actual procedure are as described. Validity of a spirometry depends on patient co-operation and criteria for acceptability and repeatability must be met for useful interpretation of the results. Commonly measured parameters are described and a simple logarithm for interpretation of a spirometry result is given. Physicians must be mindful when interpreting the result in the context of extreme of ages, size or differing ethnicity as reference values for these groups of individuals are often extrapolated and not validated

Micro CEX vs Mini CEX: Less can be more

Introduction: The mini-Clinical Evaluation Exercise (CEX) is meant to provide on the spot feedback to trainees. We hypothesised that an ultra-short assessment tool with just one global entrustment scale (micro-CEX) would encourage faculty to provide better feedback compared to the traditional multiple domain mini-CEX. Methods: 59 pairs of faculty and trainees from internal medicine completed both the 7-item mini-CEX and a micro-CEX and were surveyed regarding their perceptions of the 2 forms. Wordcount and specificity of the feedback was assessed. Participants were subsequently interviewed to elicit their views on factors affecting the utility of the CEX. Results: Quantity and quality of feedback increased with the micro-CEX compared to the mini-CEX. Wordcount increased from 9.5 to 17.5 words, and specificity increased from 1.6 to 2.3 on a 4-point scale, p < 0.05 in both cases. Faculty and residents both felt the micro-CEX provided better assessment and feedback. The micro-CEX, but not the mini-CEX, was able to discriminate between residents in different years of training. The mini-CEX showed a strong halo effect between different domains of scoring. In interviews, ease of administration, immediacy of assessment, clarity of purpose, structuring of desired feedback, assessor-trainee pairing and alignment with trainee learning goals were identified as important features to optimize utility of the (mini or micro or both) CEX. Conclusions: Simplifying the assessment component of the CEX frees faculty to concentrate on feedback and this improves both quantity and quality of feedback. How the form is administered on the ground impacts its practical utility

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

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

Acceptance and Adherence to Continuous Positive Airway Pressure Therapy in patients with Obstructive Sleep Apnea (OSA) in a Southeast Asian privately funded healthcare system

Background: There is limited data on long term Continuous Positive Airway Pressure (CPAP) adherence in Southeast Asian countries. This is a prospective study on CPAP adherence among Obstructive sleep apnea (OSA) patients in a Southeast Asian privately funded healthcare system. Methods: Patients with moderate-severe OSA who had been initiated on CPAP at least one year previously were contacted for a scripted telephone interview to assess compliance and factors associated with CPAP adherence. Results: Of 135 consecutive patients diagnosed to have moderate to severe OSA, 78 (57.8%) were initiated on CPAP treatment while 57 (42.2%) rejected CPAP upfront. 41 (52.6%) who initiated CPAP remained adherent at one year. OSA severity (AHI, ODI) and symptomatic improvement after CPAP were associated with better adherence. Presence of machine related side effects was associated with lower adherence. Inconvenience, cost and poor disease perception were reported as major barriers to uptake of CPAP therapy. Conclusions: In this Southeast Asian privately funded healthcare system, almost half of all patients with significant OSA rejected CPAP treatment upfront, but adherence among those who started CPAP is comparable to other reports. Challenges with CPAP acceptance as well as CPAP adherence need to be addressed to improve outcomes

A Pleural Effusion with an Unusual Cause

A 35-year-old presented with an incidental finding of a small left pleural effusion on a routine chest radiograph. A diagnostic pleurocentesis revealed a chylous effusion. CT showed a small left pleural effusion, multiple small pulmonary nodules and thickened interstitial lines in the right lung. Video-assisted thoracoscopic biopsy of the right lung revealed features consistent with diffuse pulmonary lymphangiomatosis