Comparison and review of abrasive bronchial brushing versus non-abrasive aspiration, lavage and washing - Higher sensitivity but with risk of over-diagnosis for bronchial brushing.

Bronchial exfoliative cytology is classified as non-abrasive (washing, aspiration and bronchoalveolar lavage) and abrasive (brushing). Brush abrasion dislodges epithelial cells but can induce bleeding and cytomorphologic artifacts. In this study, the largest cohort to date of bronchial cytology specimens were referenced against bronchial biopsy as the reference standard. Findings in the study will be useful for selecting biopsy modality and reducing necessary procedural risks. All consecutive bronchial cytology and bronchial biopsy from 1995 to 2022 were retrieved. The diagnoses were reviewed and categorized into five-tiered diagnostic categories to compare diagnostic agreement and concordance. Review of 14,148 specimens yielded 3963 non-abrasive, 2378 abrasive cytology specimens matched to biopsy, with 4355 matches between non-abrasive and abrasive cytology specimens. Agreement between non-abrasive and abrasive cytology was moderate (κ = 0.580), and similar when referenced against biopsy (κ = 0.456 (non-abrasive), κ = 0.498 (abrasive)). Abrasive bronchial cytology showed a higher percentage of malignant diagnosis (20.95 % vs. 12.63 %, p < 0.001) and over-diagnosis rate (36.40 % vs. 29.79 %, p < 0.001), but higher sensitivity (0.747 vs. 0.572, p = 0.002). For subgroup analysis of transbronchial biopsies, matched abrasive cytology showed higher discordant rates (p < 0.05) and lower accuracy (0.907 vs. 0.873, p = 0.020). With the added bleeding risk associated with brushing, abrasive techniques may only be preferable in cases with clinical or bronchoscopic suspicion of malignancy, in particular endobronchial mucosal lesions. For routine bronchoscopy, non-abrasive bronchial cytology appears to be adequate.

Respiratory admissions before and during the COVID-19 pandemic with mediation analysis of air pollutants, mask-wearing and influenza rates.

BACKGROUND AND OBJECTIVE: Decline in hospitalizations for various respiratory diseases has been reported during the COVID-19 pandemic, but what led to such an observation is uncertain. METHODS: This was a territory-wide, retrospective cohort study involving all public hospital admissions in Hong Kong from 1 January 2017 to 31 December 2020. Hospital admissions for respiratory diseases, including asthma, COPD and non-COVID pneumonia, were assessed. COVID-related admissions were excluded from this study. The time of commencement of the pandemic was taken from the fourth week of January 2020. The associations between air pollutant levels, influenza and mask-wearing rates with hospital admissions were assessed by mediation analyses. RESULTS: There were altogether 19,485, 78,693 and 238,781 admissions for asthma, COPD and non-COVID pneumonia from January 2017 to December 2020. There was a marked reduction in hospital admissions of asthma, COPD and non-COVID pneumonia (37%, 36% and 12% decrease in average daily admissions, respectively) during the COVID-19 pandemic compared to before. Air pollutant levels and influenza rate were decreased while mask-wearing rate was increased. Collinearity of mask-wearing rates and pandemic year was observed. For COPD, NO2 , SO2 , PM10 and influenza rates (4%, 11%, 4% and 4% of the total effect, respectively), while for non-COVID pneumonia, PM10 and influenza rates (11% and 52%, respectively) had significant mediation effect on changes in hospital admissions before and during the COVID-19 pandemic. CONCLUSION: During the COVID-19 pandemic, a decrease in air pollutant levels and influenza rate had mediation effect on the reduction in hospitalizations of COPD and non-COVID pneumonia.

Bronchial cytology of pulmonary adenoid cystic carcinoma - A multi-institute series with emphasis on immunocytochemistry.

BACKGROUND: Pulmonary adenoid cystic carcinoma (AdCC) is a central and superficial primary lung neoplasm, well-suited for sampling by bronchial cytology. This study aims to review the cytologic features of pulmonary AdCC on bronchial cytology, and to report an experience of applying immunocytochemistry on this rare entity. METHODS: A multi-institute review of bronchial cytology specimens from histologically proven pulmonary AdCCs was performed. Published cases of bronchial cytology of pulmonary AdCC were reviewed. The cytologic features and immunocytochemical profile for pulmonary AdCC was summarized and compared with pertinent differentials. RESULTS: A total of 16 specimens from eight patients were retrieved. The initial cytologic diagnoses were negative (n = 7), atypia (n = 6), suspicious (n = 2) and AdCC (n = 1). Retrospective review showed eight bronchial cytology specimens (including five cases of atypia) with tumor cells present. The tumor cells displayed small basaloid nuclei with occasional small nucleoli, mild nuclear atypia, and scanty cytoplasm. Architectural patterns observed included clusters, tubules, solid sheets, three-dimensional balls, papillary-like fronds, and complex cribriform structures. Basement-membrane-like material, free or associated with tumor cells, were seen in all cases. Immunocytochemistry was performed in one specimen. MYB was positive. TTF-1, synaptophysin and chromogranin were negative. Epithelial and basal markers demonstrated a dual cell population. Literature review yielded 28 cases. Cytologic features described were similar except for cytoplasmic vacuolation in one case. CONCLUSION: Basement membrane-like material is specific for AdCC. MYB positivity, TTF-1 and neuroendocrine marker negativity, support a diagnosis of AdCC. Other immunocytochemistry and cytologic features overlap significantly with adenocarcinoma and small cell carcinoma of lung.

Detection of early (T1) lung cancers and lepidic adenocarcinomas in sputum and bronchial cytology.

BACKGROUND: The lung is an extensively epithelialized organ, producing ample exfoliated material for sputum and bronchial cytology. In view of the updates in the World Health Organization classification of early (T1/≤ 3 cm) lung cancer with respect to adenocarcinomas with lepidic pattern, this study retrospectively reviews sputum and bronchial cytology paired with resection-confirmed lung cancers. METHODS: A computerized search for all lung resection specimens of carcinomas over a 20-year period was performed. Cytologic diagnoses of corresponding sputum and bronchial cytology were classified into five-tiered categories (C1-insufficient/inadequate, C2-benign, C3-atypia, C4-suspicious and C5-malignant). Reports and slides of the resection specimen were reviewed for reclassification of T1 cancers. RESULTS: Totally 472 and 383 sputum and bronchial cytology specimens respectively were included. Sensitivity for T1 lesions on sputum cytology were 10.6 %, 2.1 % and 0.5 % at cutoffs of atypia/C3, suspicious/C4 and malignant/C5 categories, lower than bronchial cytology (35.1 %, 15.5 %, 8.1 %; p < 0.001). T1 lesions correlated with lower detection rates, whereas squamous cell carcinoma histology, larger size and bronchial invasion were associated with increased detection rates in sputum and bronchial cytology (p < 0.050). Detection rates for abrasive bronchial cytology (brushing) were overall higher (p = 0.018- < 0.001), but on subgroup comparison, non-abrasive (aspiration, lavage and washing) cytology demonstrated favorable trends (p = 0.063-0.088) in detecting T1 lesions. Adenocarcinomas with lepidic pattern had lower suspicious/C4 (p = 0.040) or above and malignant/C5 (p = 0.019), but not atypia/C3 or above (p = 0.517) rates. CONCLUSIONS: Most adenocarcinomas with lepidic pattern are only diagnosed as atypia/C3 on cytology. With its modest sensitivity, interpretation of negative and indeterminate cytology results mandates caution.

Continuous Positive Airway Pressure Does Not Improve Nonalcoholic Fatty Liver Disease in Patients with Obstructive Sleep Apnea. A Randomized Clinical Trial.

Rationale: Obstructive sleep apnea (OSA) is associated with development of nonalcoholic fatty liver disease (NAFLD). The effects of continuous positive airway pressure (CPAP) on NAFLD in patients with concomitant OSA are unknown.Objectives: To investigate the effects of autoadjusting CPAP versus subtherapeutic CPAP treatment over 6 months on NAFLD activities.Methods: Patients with NAFLD and OSA, as defined by respiratory event index ≥5/h diagnosed by a validated level 3 Embletta device, were randomized into group A) autoadjusting CPAP (4-20 cm H2O) or group B) subtherapeutic CPAP (pressure fixed at 4 cm H2O). The primary endpoint was the difference in changes in intrahepatic triglyceride as measured by proton magnetic resonance spectroscopy after 6 months of therapy. Key secondary endpoints included changes in controlled attenuation parameter (CAP) and liver stiffness measurement measured with transient elastography, and serum cytokeratin-18 fragment.Measurements and Main Results: A total of 120 patients were randomized equally into two groups. There were significant correlations between CAP and respiratory event index (r = 0.203, P = 0.026), percentage of total recording time with SaO2 < 90% (r = 0.265, P = 0.003), and oxygen desaturation index (r = 0.214, P = 0.019). After 6 months of treatment, there were no significant differences of changes in primary and secondary endpoints between the two treatment groups. Regression analysis showed that weight change over 6 months correlated with changes in both intrahepatic triglyceride and CAP (P < 0.001).Conclusions: Despite significant correlations between hepatic steatosis and markers of severity of OSA, CPAP alone did not improve hepatic steatosis and fibrosis. However, the additional role of weight reduction through lifestyle modification deserves further investigation.

Effect of short-course exercise training on the frequency of exacerbations and physical activity in patients with COPD: A randomized controlled trial.

BACKGROUND AND OBJECTIVE: Previous studies have suggested that early pulmonary rehabilitation (PR) programmes post-AECOPD are an effective and safe intervention for reducing hospital admissions and improving quality of life. This study assessed whether a short course of exercise training post-AECOPD with periodic reinforcement exercise training and phone call reminders reduces readmissions and increases physical activity in COPD patients. METHODS: Subjects were randomized into either the (i) intervention group (IG), consisting of 4-8 weeks of training supervised by a physiotherapist and phone contact every 2 weeks by a case manager providing support and reinforcement of continuous exercise at home or (ii) usual care group (UG), which had no input by a physiotherapist or case manager. Readmissions were assessed at 12 months. Activities of all patients were assessed by an activity monitor at baseline, 3 and 12 months. RESULTS: Altogether, 136 subjects were included and randomized (68 in IG and 68 in UG). The age, gender and FEV1 % predicted were 75.0 ± 6.7 years, 132 males and 47.0 ± 16.2%, respectively. The mean number of readmissions for AECOPD (1.06 vs 1.72 times, P = 0.014) was less and time to first readmission was increased (146.8 vs 122.4 days, P = 0.005) in the IG versus UG at 12 months. At 12 months, there was no change in activity measured by activity monitor between the two groups. CONCLUSION: This programme decreased exacerbation frequency and increased the time of readmissions for AECOPD. It did not improve physical activities and exercise tolerance at 12 months.

Blood eosinophil count as a predictor of hospital length of stay in COPD exacerbations.

BACKGROUND AND OBJECTIVE: Airway inflammation accompanying exacerbations varies among individuals with some having neutrophilic, while others showing eosinophilic inflammation. This study assessed the cut-off values of blood eosinophil count for identifying subjects with longer hospital length of stay (LOS) with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). METHODS: Patients were recruited at presentation to the hospital with an AECOPD. Complete blood picture with differential count was taken on admission. Patients were treated with a standard course of systemic corticosteroid and antibiotic and evaluated at 8 weeks post-exacerbation for lung function measurement and 6-min walk. They were followed up in 1 year for any readmissions or mortality. Cut-off values of eosinophils for assessment of longer LOS were calculated using receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 346 patients with admission eosinophil count were included in the analysis (333 (96.2%) were males; mean ± SD age: 74.9 ± 7.8 years; mean forced expiratory volume in 1 s (FEV1 ): 43.4 ± 16.3% predicted). The median (interquartile range (IQR)) of the absolute peripheral eosinophil count, percent eosinophil count and LOS were 0.11 (0.25) × 109 /L, 1 (3) % and 5 (7) days, respectively. Using the median LOS of ≥5 days as the cut-off, ROC analysis of the cut-off value of eosinophil count associated with longer LOS was at <2% (area under the curve (AUC): 0.666, P < 0.001) while absolute eosinophil count was at <0.144 × 109 /L (AUC: 0.645, P < 0.001). These eosinophil cut-off values could predict longer LOS independent of age, lung function and previous hospital admissions, but had no association with readmissions for AECOPD and mortality at 12 months. CONCLUSION: An eosinophil value of <0.144 × 109 /L on admission or <2% was associated with longer hospital LOS for AECOPD.

Molecular detection of respiratory pathogens and typing of human rhinovirus of adults hospitalized for exacerbation of asthma and chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and asthma are associated with a variety of precipitating factors including infection. This study assessed the infective viral etiologies by real-time multiplex polymerase chain reaction of patients hospitalized with AECOPD and asthma exacerbations. In addition, infective etiologies were assessed for association with the clinical outcome of the patients. METHODS: Adults admitted with AECOPD and asthma exacerbations between August 2016 and July 2017 were recruited. Nasopharyngeal aspirate (NPA) samples were obtained from the patients within 1-2 days of admission and subjected to pathogen detection and human rhinovirus (HRV) typing. RESULTS: Altogether 402 patients with AECOPD, 80 stable COPD, 100 asthma exacerbation and 21 stable asthma subjects were recruited. Among those admitted for AECOPD and asthma exacerbations, 141(35.1%) and 45(45.0%) respectively had pathogens identified in the NPA specimens. The commonest virus identified was influenza A followed by HRV. HRV typing identified HRV-A and HRV-C as the more common HRV with a wide variety of genotypes. Identification of pathogens in NPA or HRV typing otherwise did not affect clinical outcomes including the hospital length of stay, readmission rates and mortality except that identification of pathogens in asthma exacerbation was associated with a lower rate of readmissions at 30 and 60 days. CONCLUSIONS: Many respiratory viruses were associated with AECOPD and asthma exacerbation. HRV-A and HRV-C were the more common HRV associated with exacerbations. Identification of pathogens in NPA was associated with less readmissions for asthma patients at 30 and 60 days. TRIAL REGISTRATION: ClinicalTrials.gov NCT02866357 .

Emerging concepts in pleural infection.

PURPOSE OF REVIEW: Pleural infection remains an important pulmonary disease, causing significant morbidity and mortality. There is a resurgence of disease burden despite introduction of antibiotics and pneumococcal vaccines. A revisit of the pathogenesis and update on intervention may improve the care of pleural infection. RECENT FINDINGS: Recent studies have uncovered the prognostic implication of the presence of a pleural effusion in patients with pneumonia. Identifying where the bacteria lives may have diagnostic and therapeutic implications. Over-exaggerated pleural inflammation may underlie development of parapneumonic effusion as indirect evidence and a randomized study in children raised a role of corticosteroids in parapneumonic pleural effusions, but data are lacking for adults. Optimization of the delivery regimen of intrapleural fibrinolytic and deoxyribonuclease therapy is ongoing. SUMMARY: The review aims to review the current practice and explore new directions of treatment on pleural infection.

Acute exacerbation of COPD.

The literature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is fast expanding. This review focuses on several aspects of acute exacerbation of COPD (AECOPD) including epidemiology, diagnosis and management. COPD poses a major health and economic burden in the Asia-Pacific region, as it does worldwide. Triggering factors of AECOPD include infectious (bacteria and viruses) and environmental (air pollution and meteorological effect) factors. Disruption in the dynamic balance between the 'pathogens' (viral and bacterial) and the normal bacterial communities that constitute the lung microbiome likely contributes to the risk of exacerbations. The diagnostic approach to AECOPD varies based on the clinical setting and severity of the exacerbation. After history and examination, a number of investigations may be useful, including oximetry, sputum culture, chest X-ray and blood tests for inflammatory markers. Arterial blood gases should be considered in severe exacerbations, to characterize respiratory failure. Depending on the severity, the acute management of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and noninvasive ventilation. Hospitalization may be required, for severe exacerbations. Nonpharmacological interventions including disease-specific self-management, pulmonary rehabilitation, early medical follow-up, home visits by respiratory health workers, integrated programmes and telehealth-assisted hospital at home have been studied during hospitalization and shortly after discharge in patients who have had a recent AECOPD. Pharmacological approaches to reducing risk of future exacerbations include long-acting bronchodilators, inhaled steroids, mucolytics, vaccinations and long-term macrolides. Further studies are needed to assess the cost-effectiveness of these interventions in preventing COPD exacerbations.

Undiagnosed airflow limitation is common in patients with coronary artery disease and associated with cardiac stress.

BACKGROUND AND OBJECTIVE: Smoking is a common risk factor for coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD). We evaluated the prevalence of undiagnosed COPD in patients with CAD and assessed the relationship between airflow obstruction and markers of cardiac stress. METHODS: We recruited prospectively consecutive patients aged >40 years without known history of chronic lung disease (e.g. asthma, COPD, bronchiectasis) who had undergone percutaneous coronary intervention (PCI) for obstructive CAD between August 2009 and October 2010. Spirometry was performed and serum ST2, a novel biomarker of cardiomyocyte stress and fibrosis, was measured by enzyme-linked immunosorbent assay. RESULTS: Among 475 subjects (mean age 64 ± 9.7, range 42-85 years, 87.2% males, 58.5% current or ex-smokers) who underwent spirometry, 51 (10.7%) had undiagnosed airflow obstruction with FEV1 /FVC ratio <70%. Of these 51 subjects, 14 (2.9%), 23 (4.8%) and 14 (2.9%) had FEV1 ≥80, 50-80 and 30-50% predicted normal, respectively. ST2 level was measured in all the subjects with undiagnosed airflow obstruction and in 290 subjects with normal lung function. There was no significant difference in left ventricular ejection fraction on echocardiogram between subjects with and without airflow obstruction. Patients with severe airflow obstruction had a higher level of cardiac stress marker ST2 than those with mild and moderate airflow obstruction (rho = -0.214, P ≤ 0.001). CONCLUSION: Undiagnosed airflow obstruction is common among patients with CAD who have undergone PCI. Severity of airflow limitation is associated with increasing cardiac stress.

Mesenteric fat thickness is associated with metabolic syndrome independently of Apnoea-Hypopnoea Index in subjects with obstructive sleep apnoea.

BACKGROUND AND OBJECTIVE: Mesenteric fat thickness (MFT) was associated with metabolic syndrome (MetS) and obstructive sleep apnoea (OSA) in separate studies. This study aimed to assess whether the association of MFT with MetS was independent of OSA in subjects with suspected OSA. METHODS: Two hundred forty-two subjects (men: 181; women: 61) with suspected OSA underwent ultrasound examinations for measurements of mesenteric, subcutaneous and preperitoneal fat thicknesses after overnight polysomnography. Anthropometric measurements and metabolic risk profile were assessed. RESULTS: Two hundred twenty-one (91%) subjects were confirmed to have OSA with Apnoea-Hypopnoea Index (AHI) >5/h. MFT had significant correlation (P < 0.01) with AHI and most MetS components. In partial correlation with adjustment for AHI, MFT had significant correlation (P < 0.01) with most MetS components including fasting plasma glucose (r = 0.25), triglycerides (r = 0.24), HDL cholesterol (r = -0.29) and waist circumference (r = 0.56). In multivariate logistic regression with adjustments for the confounding variables including AHI, MFT was the only variable independently associated with MetS, with the odds ratio of 5.48 (95% CI: 1.5-20.0) for every 1 cm increase of MFT. When the subjects were subdivided into obese (BMI ≥ 27.5 kg/m(2) ) and non-obese (BMI < 27.5 kg/m(2) ) groups, the positive association of MFT with MetS persisted in the non-obese group only, with the odds ratio of 22 (95% CI 2.8-174.1) for every 1 cm increase of MFT. The AHI had significant association with MetS in male subjects only. CONCLUSION: MFT, rather than AHI, is the major independent determinant of MetS in subjects with suspected OSA, particularly in non-obese subjects. See Editorial, page 408.

Digital Image Comparison of Cellular Yield in Bronchial Brushing: Pre- and Post-Biopsy Lavage Cytology.

INTRODUCTION: Bronchoscopy is a useful diagnostic tool capable of performing core biopsy, forceps biopsy, bronchoalveolar lavage, and bronchial brushing. This study compares the cellularity of bronchial cytology including pre- and post-biopsy lavage by digital image analysis, aiming to increase diagnostic and tumor yield by optimizing the sequence and combination of bronchial biopsy and cytology. METHODS: Alveolar macrophage, bronchial epithelium, and tumor cell cellularity from liquid-based cytology preparations of bronchial brushing and pre-biopsy and post-biopsy bronchoalveolar lavage were annotated on digitized whole-slide images and compared. Secondary analysis on the relationship of tumor cell and non-lesional cell yield was performed. RESULTS: Overall, 118 cytology specimens from 43 patients were retrieved in total. Bronchial epithelium count was higher in pre-biopsy than post-biopsy lavage (p < 0.01) but not for alveolar macrophages nor tumor cell (p > 0.05). Tumor cell count was higher for bronchial brushing cytology samples than lavage (p = 0.018). The alveolar macrophage count was higher in post-biopsy lavage than bronchial brushing (p = 0.033); otherwise, brushing showed consistently higher bronchial epithelium and tumor cell counts. There were 33 false negative (tumor cell absent) specimens, and the combination of bronchial brushing and pre-biopsy lavage yielded the lowest false negative cases. Correlation between bronchial epithelium and alveolar macrophage counts with tumor cell count was weak (correlation coefficient = -0.168-0.203) except for post-biopsy lavage (correlation coefficient = 0.412-0.479, p < 0.05). CONCLUSION: Bronchial brushing yields a greater amount of tumor cell than lavage, and timing lavage before or after core biopsy does not affect tumor cell yield. Combining bronchial brushing and pre-biopsy lavage results in the lowest false negative rate.

A comparative study of diagnostic accuracy in 3026 pleural biopsies and matched pleural effusion cytology with clinical correlation.

BACKGROUND: Pleural effusion can be caused by a wide range of benign and malignant conditions. Pleural biopsy and effusion cytology represent two key methods of pathological diagnosis. To compare the performance these two methods, a large cohort of matched pleural biopsy and effusion cytology with clinical follow-up was reviewed. METHODS: Pleural biopsies and effusion cytology specimens over a period of 18 years were retrieved. Cytology specimens collected within 7 days of pleural biopsy were matched. Reports were reviewed, and the cause for pleural effusion was determined by hospital disease coding and clinical data. RESULTS: Totally, 3026 cases were included. The leading cause of benign effusion was tuberculosis (n = 650). Malignant pleural effusion (MPE) was more common in older females (p < 0.001) and mostly due to lung cancer (n = 959), breast cancer (n = 64), and mesothelioma (n = 48). The inadequate/insufficient (B1/C1) rate of biopsy was higher than cytology (15.6% vs. 0.3%) but the rates for other diagnostic categories were similar. Biopsy and cytology showed a correlation coefficient of 0.315, improving to 0.449 when inadequate/insufficient (B1/C1) cases were excluded. The ROM for benign cytology (C2) was lower than biopsy (B2) (p < 0.001). Compared with biopsy, the diagnostic accuracy was higher in cytology overall and for metastatic carcinomas (p < 0.001) but lower for hematolymphoid malignancies (p = 0.014) and mesotheliomas (p = 0.002). CONCLUSIONS: These results suggest that effusion cytology may be better for confirming benignity and diagnosing carcinomatous MPE. In these cases, pleural biopsy may be withheld to reduce procedural risks. However, for suspected hematolymphoid malignancies and mesothelioma, biopsy should be considered.

1-Year Prospective Study of the Relationship of Serial Exhaled Nitric Oxide Level and Asthma Control.

Background and Objective: Previous studies found that the fractional nitric oxide concentration in exhaled breath (FeNO) levels in healthy Chinese adults was higher than in White adults. More understanding of serial changes of FeNO levels with asthma control in a real-life clinical setting would be important to explore the utility of this biomarker in routine asthma management. This study assessed the FeNO levels of Chinese asthma subjects with different levels of asthma control and the serial changes with respect to the changes in asthma control over 1 year. Methods: A 12-month prospective study (subjects recruited between November 2019 and January 2021) with serial measurement of FeNO levels at baseline, 4, 8 and 12 months. Asthma control was assessed by the Global Initiative for Asthma classification, Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ). Results: Altogether, 136 subjects (mean age 51.51±15.09 years, 46[33.8%] male) had successful baseline FeNO measurements. At baseline, the FeNO levels did not show a statistically significant difference for controlled, partly controlled and uncontrolled asthma according to GINA classification, ACT and ACQ. FeNO levels decreased with improving asthma control and stayed at similar levels with unchanged or worsening asthma control for all subjects. For subjects with baseline blood eosinophil levels ≥300 cells/µL(n=59), FeNO levels decreased with improving asthma control, stayed similar without change for asthma control and increased with worsening asthma control. Receiver operating characteristic (ROC) analysis with the highest area under curve (AUC) for changes in FeNO levels for improving asthma control was between ≤ -10 to -25 ppb at various time points in the 12-month study. Conclusion: Changes in FeNO levels over time were associated with changes in clinical asthma control, particularly in those with higher blood eosinophil count and are likely more useful than a single time point measurement in managing asthma.

Phenotyping empyema by pleural fluid culture results and macroscopic appearance: an 8-year retrospective study.

Background: The clinical impact of phenotyping empyema is poorly described. This study was designed to evaluate clinical characteristics and outcomes based on the two readily available parameters, pleural fluid culture status and macroscopic fluid appearance. Methods: A retrospective study was conducted on patients with empyema hospitalised between 2013 and 2020. Empyema was classified into culture-positive empyema (CPE) or culture-negative empyema (CNE) and pus-appearing empyema (PAE) or non-pus-appearing empyema (non-PAE) based on the pleural fluid culture status and macroscopic fluid appearance, respectively. Results: Altogether, 212 patients had confirmed empyema (CPE: n=188, CNE: n=24; PAE: n=118, non-PAE: n=94). The cohort was predominantly male (n=163, 76.9%) with a mean age of 65.0±13.6 years. Most patients (n=180, 84.9%) had at least one comorbidity. Patients with CPE had higher rates of in-hospital mortality (19.1% versus 0.0%, p=0.017) and 90-day mortality (18.6% versus 0.0%, p=0.017) and more extrapulmonary sources of infection (29.8% versus 8.3%, p=0.026) when compared with patients with CNE. No significant difference in mortality rate was found between PAE and non-PAE during the in-hospital stay and at 30 days and 90 days. Patients with PAE had less extrapulmonary sources of infection (20.3% versus 36.2%, p=0.010) and more anaerobic infection (40.9% versus 24.5%, p=0.017) than those with non-PAE. The median RAPID (renal, age, purulence, infection source, and dietary factors) scores were higher in the CPE and non-PAE groups. After adjusting for covariates, culture positivity was not independently associated with mortality on multivariable analysis. Conclusion: Empyema is a heterogeneous disease with different clinical characteristics. Phenotyping empyema into different subclasses based on pleural fluid microbiological results and macroscopic fluid appearance provides insight into the underlying bacteriology, source of infection and subsequent clinical outcomes.

Changing pleural fluid triglyceride levels in cirrhotic chylothorax.

Chylothorax is an uncommon disease entity, but it occasionally poses a diagnostic challenge to physicians. Pleural fluid triglyceride level has been advocated as a screening test to diagnose chylothorax. However, its level can be depressed if there is an additional pathology driving the process of pleural fluid production. We report a case of high-volume pleural fluid output due to dual pathologies, cirrhotic hydrothorax and chylothorax, causing an initial failure to diagnose chylothorax due to low pleural fluid triglyceride level. The fluid triglyceride levels were unmasked after the treatment for underlying portal hypertension. These findings were further substantiated by positive lipoprotein electrophoresis for chylomicron. In this patient, lipoprotein electrophoresis of his pleural fluid specimen helps distinguish chylothorax as a second pathology amidst the underlying cirrhotic hydrothorax.

A territory-wide study on the factors associated with recurrent asthma exacerbations requiring hospitalization in Hong Kong.

BACKGROUND: The real-world relationships between the demographic and clinical characteristics of asthma patients, their prehospitalization management and the frequency of hospitalization due to asthma exacerbation is poorly established. OBJECTIVE: To determine the risk factors of recurrent asthma exacerbations requiring hospitalizations and evaluate the standard of baseline asthma care. METHODS: A territory-wide, multicentre retrospective study in Hong Kong was performed. Medical records of patients aged ≥18 years admitted to 11 acute general hospitals from January 1 to December 31, 2016 for asthma exacerbations were reviewed. RESULTS: There were 2280 patients with 3154 admissions (36.7% male, median age 66.0 [interquartile range: 48.0-81.0] years, 519 had ≥2 admissions). Among them, 1830 (80.3%) had at least one asthma-associated comorbidity, 1060 (46.5%) and 885 (38.9%) of patients had Accident and Emergency Department (AED) attendance and hospitalization in the preceding year, respectively. Patients with advancing age (incidence rate ratio [IRR]: 1.003 for every year increment), a history of AED visits or hospitalization (IRR: 1.018 and 1.070 for every additional episode, respectively) for asthma exacerbation in the preceding year, the presence of neuropsychiatric (IRR: 1.142) and gastrointestinal (IRR: 1.154) comorbidities were risk factors for an increasing number of admissions for asthma exacerbation. For patients with ≥2 admissions, 17.1% were not prescribed inhaled corticosteroid and only 44.6% had spirometry checked before the index admission. Asthma phenotyping was often incomplete, as assessment of atopy (total serum immunoglobulin E level and senitization to aeroallergens) was only performed in 30 (5.8%) patients with ≥2 admissions. CONCLUSIONS AND CLINICAL RELEVANCE: Improving asthma care, especially in elderly patients with a prior history of urgent healthcare utilization and comorbidities, may help reduce healthcare burden. Suboptimal management before the index admission was common in patients hospitalized for asthma exacerbations. Early identification of patients at risk and enhancement of baseline asthma management may help to prevent recurrent asthma exacerbation and subsequent hospitalization.

High-pressure leakage of pleural fluid through the healed entry site of the indwelling pleural catheter from undrained locules.

The indwelling pleural catheter (IPC) is an established treatment for recurrent pleural effusion. Fluid leakage through the IPC insertion tract has been reported, but its occurrence is only limited to a short period after the procedure. Besides, the drainage efficacy of IPC may be limited by the presence of loculation in the pleural space, especially when intrapleural fibrinolytic is contraindicated. We report a case of fluid leakage through the healed entry site of IPC due to high pressure built from undrained pleural fluid locules, which was successfully treated with an additional drain targeting the largest undrained locule.