Continuous positive airway pressure improves blood pressure and serum cardiovascular biomarkers in obstructive sleep apnoea and hypertension.

BACKGROUND: The impact of treatment for obstructive sleep apnoea (OSA) on reduction of cardiovascular risk is unclear. This study aimed to examine the effect of continuous positive airway pressure (CPAP) on ambulatory blood pressure (BP) and subclinical myocardial injury in subjects with OSA and hypertension. METHODS: This was a parallel-group randomised controlled trial. Subjects with hypertension requiring at least three antihypertensive medications and moderate-to-severe OSA were enrolled. Eligible subjects were randomised (1:1) to receive either CPAP treatment or control (no CPAP) for 8 weeks. Changes in ambulatory BP and serum biomarkers were compared. Stratified analysis according to circadian BP pattern was performed. RESULTS: 92 subjects (75% male; mean±sd age 51±8 years and apnoea-hypopnoea index 40±8 events·h-1, taking an average of 3.4 (range 3-6) antihypertensive drugs) were randomised. The group on CPAP treatment, compared with the control group, demonstrated a significant reduction in 24-h systolic BP (-4.4 (95% CI -8.7- -0.1) mmHg; p=0.046), 24-h diastolic BP (-2.9 (95% CI -5.5- -0.2) mmHg; p=0.032), daytime systolic BP (-5.4 (95% CI -9.7- -1.0) mmHg; p=0.016) and daytime diastolic BP (-3.4 (95% CI -6.1- -0.8) mmHg; p=0.012). CPAP treatment was associated with significant BP lowering only in nondippers, but not in dippers. Serum troponin I (mean difference -1.74 (95% CI -2.97- -0.50) pg·mL-1; p=0.006) and brain natriuretic peptide (-9.1 (95% CI -17.6- -0.6) pg·mL-1; p=0.036) were significantly reduced in CPAP compared with the control group. CONCLUSIONS: In a cohort with OSA and multiple cardiovascular risk factors including difficult-to-control hypertension, short-term CPAP treatment improved ambulatory BP, and alleviated subclinical myocardial injury and strain.

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.

When compared to plasma-based detection, osimertinib-treated non-small cell lung cancer (NSCLC) with tissue rebiopsy-confirmed acquired T790M mutation is associated with better survival.

BACKGROUND: Osimertinib has been approved by the Food and Drug Administration (FDA) of the United States (US) for the treatment of progressive non-small cell lung cancer (NSCLC) that has acquired T790M mutation during treatment with first-line epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI). We compared the progression-free survival (PFS) of patients whose T790M mutation was identified by tissue rebiopsy with those by plasma-based biopsy. METHODS: This is a retrospective single-center cohort study conducted in Queen Mary Hospital, Hong Kong S.A.R. that included 118 Chinese patients with advanced NSCLC who had disease progression after treatment with a first-line EGFR tyrosine kinase inhibitor and received osimertinib upon detection of T790M mutation, either by tissue rebiopsy or plasma-based biopsy (by identification of circulating tumor DNA in the peripheral circulation). The primary endpoint is PFS. RESULTS: Patients with T790M mutation detected by tissue rebiopsy (n = 22) had significantly better PFS than those by plasma-based biopsy (n = 96) (median PFS: 415 vs 224 days, P = .018) Hazard ratio for PFS, in favor of the tissue rebiopsy group, was 0.496 (95% confidence interval [CI]: 0.277-0.889). CONCLUSIONS: For patients who have NSCLC that progressed after first-line EGFR-TKI, rebiopsy by peripheral blood liquid biopsy and tissue rebiopsy for T790M mutation may have prognostic implication in terms of differences in PFS.

A 47-Year-Old Woman With Hemoptysis and a Lung Cyst.

CASE PRESENTATION: A 47-year-old woman was admitted to the hospital for an episode of hemoptysis. She coughed out small amount of clotted blood the morning of admission. She had no other symptoms on further review. Her medical history was unremarkable with the exception of an upper respiratory tract infection 9 months previously. She did not have any significant medical history or recent sick contacts. She was a lifelong nonsmoker and the mother of three teenaged children. She had irregular menses for the past 2 years, and her last menstrual period was 3 months ago. She reliably reported not engaging in any sexual contact for the past 2 years.

Detection of COVID-19 Using Deep Learning Algorithms on Chest Radiographs.

PURPOSE: To evaluate the performance of a deep learning (DL) algorithm for the detection of COVID-19 on chest radiographs (CXR). MATERIALS AND METHODS: In this retrospective study, a DL model was trained on 112,120 CXR images with 14 labeled classifiers (ChestX-ray14) and fine-tuned using initial CXR on hospital admission of 509 patients, who had undergone COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR). The test set consisted of a CXR on presentation of 248 individuals suspected of COVID-19 pneumonia between February 16 and March 3, 2020 from 4 centers (72 RT-PCR positives and 176 RT-PCR negatives). The CXR were independently reviewed by 3 radiologists and using the DL algorithm. Diagnostic performance was compared with radiologists' performance and was assessed by area under the receiver operating characteristics (AUC). RESULTS: The median age of the subjects in the test set was 61 (interquartile range: 39 to 79) years (51% male). The DL algorithm achieved an AUC of 0.81, sensitivity of 0.85, and specificity of 0.72 in detecting COVID-19 using RT-PCR as the reference standard. On subgroup analyses, the model achieved an AUC of 0.79, sensitivity of 0.80, and specificity of 0.74 in detecting COVID-19 in patients presented with fever or respiratory systems and an AUC of 0.87, sensitivity of 0.85, and specificity of 0.81 in distinguishing COVID-19 from other forms of pneumonia. The algorithm significantly outperforms human readers (P<0.001 using DeLong test) with higher sensitivity (P=0.01 using McNemar test). CONCLUSIONS: A DL algorithm (COV19NET) for the detection of COVID-19 on chest radiographs can potentially be an effective tool in triaging patients, particularly in resource-stretched health-care systems.

Development and validation of risk prediction models for COVID-19 positivity in a hospital setting.

OBJECTIVES: To develop: (1) two validated risk prediction models for coronavirus disease-2019 (COVID-19) positivity using readily available parameters in a general hospital setting; (2) nomograms and probabilities to allow clinical utilisation. METHODS: Patients with and without COVID-19 were included from 4 Hong Kong hospitals. The database was randomly split into 2:1: for model development database (n = 895) and validation database (n = 435). Multivariable logistic regression was utilised for model creation and validated with the Hosmer-Lemeshow (H-L) test and calibration plot. Nomograms and probabilities set at 0.1, 0.2, 0.4 and 0.6 were calculated to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: A total of 1330 patients (mean age 58.2 ± 24.5 years; 50.7% males; 296 COVID-19 positive) were recruited. The first prediction model developed had age, total white blood cell count, chest x-ray appearances and contact history as significant predictors (AUC = 0.911 [CI = 0.880-0.941]). The second model developed has the same variables except contact history (AUC = 0.880 [CI = 0.844-0.916]). Both were externally validated on the H-L test (p = 0.781 and 0.155, respectively) and calibration plot. Models were converted to nomograms. Lower probabilities give higher sensitivity and NPV; higher probabilities give higher specificity and PPV. CONCLUSION: Two simple-to-use validated nomograms were developed with excellent AUCs based on readily available parameters and can be considered for clinical utilisation.

Role of early definitive management for newly diagnosed malignant pleural effusion related to lung cancer.

BACKGROUND AND OBJECTIVE: The advent of effective anti-cancer therapy has brought about uncertainty on the benefit of early definitive measures for newly diagnosed MPE from lung cancer. This study aims to investigate the outcomes of MPE in this setting. METHODS: Lung cancer patients with MPE at first presentation to a tertiary care hospital were followed up till death or censored from 2011 to 2018. Early MPE control measures included chemical pleurodesis or IPC before or shortly after oncological treatment. Predictors of time to MPE re-intervention were identified with Cox proportional hazard analyses. RESULTS: Of the 509 records screened, 233 subjects were eligible. One hundred and twenty-seven subjects received oral targeted therapy as first-line treatment and 34 (26.8%) underwent early definitive MPE control measures. Early MPE control measures in addition to targeted therapy, as compared to targeted therapy alone, significantly reduced the subsequent need of MPE re-intervention (23.5% vs 53.8%, P = 0.002). Similar benefits from MPE control measures were found in groups receiving systemic anti-cancer therapy or best supportive care (0% vs 52%, P = 0.003; 18% vs 56.7%, P = 0.024, respectively). In the group with targetable mutations, both early MPE control measures (HR: 0.25, 95% CI: 0.12-0.53, P < 0.001) and the use of targeted therapy (HR: 0.22, 95% CI: 0.10-0.46, P < 0.001) were independently associated with longer time to MPE re-interventions. CONCLUSION: Early MPE control measures in lung cancer has additional benefits on reducing the need and prolonging the time to MPE re-intervention, independent of anti-cancer therapies.

Frequency and Distribution of Chest Radiographic Findings in Patients Positive for COVID-19.

Background Current coronavirus disease 2019 (COVID-19) radiologic literature is dominated by CT, and a detailed description of chest radiography appearances in relation to the disease time course is lacking. Purpose To describe the time course and severity of findings of COVID-19 at chest radiography and correlate these with real-time reverse transcription polymerase chain reaction (RT-PCR) testing for severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, nucleic acid. Materials and Methods This is a retrospective study of patients with COVID-19 confirmed by using RT-PCR and chest radiographic examinations who were admitted across four hospitals and evaluated between January and March 2020. Baseline and serial chest radiographs (n = 255) were reviewed with RT-PCR. Correlation with concurrent CT examinations (n = 28) was performed when available. Two radiologists scored each chest radiograph in consensus for consolidation, ground-glass opacity, location, and pleural fluid. A severity index was determined for each lung. The lung scores were summed to produce the final severity score. Results The study was composed of 64 patients (26 men; mean age, 56 years ± 19 [standard deviation]). Of these, 58 patients had initial positive findings with RT-PCR (91%; 95% confidence interval: 81%, 96%), 44 patients had abnormal findings at baseline chest radiography (69%; 95% confidence interval: 56%, 80%), and 38 patients had initial positive findings with RT-PCR testing and abnormal findings at baseline chest radiography (59%; 95% confidence interval: 46%, 71%). Six patients (9%) showed abnormalities at chest radiography before eventually testing positive for COVID-19 with RT-PCR. Sensitivity of initial RT-PCR (91%; 95% confidence interval: 83%, 97%) was higher than that of baseline chest radiography (69%; 95% confidence interval: 56%, 80%) (P = .009). Radiographic recovery (mean, 6 days ± 5) and virologic recovery (mean, 8 days ± 6) were not significantly different (P = .33). Consolidation was the most common finding (30 of 64; 47%) followed by ground-glass opacities (21 of 64; 33%). Abnormalities at chest radiography had a peripheral distribution (26 of 64; 41%) and lower zone distribution (32 of 64; 50%) with bilateral involvement (32 of 64; 50%). Pleural effusion was uncommon (two of 64; 3%). The severity of findings at chest radiography peaked at 10-12 days from the date of symptom onset. Conclusion Findings at chest radiography in patients with coronavirus disease 2019 frequently showed bilateral lower zone consolidation, which peaked at 10-12 days from symptom onset. © RSNA, 2020.

Imaging Profile of the COVID-19 Infection: Radiologic Findings and Literature Review.

PURPOSE: To present the findings of 21 coronavirus disease 2019 (COVID-19) cases from two Chinese centers with CT and chest radiographic findings, as well as follow-up imaging in five cases. MATERIALS AND METHODS: This was a retrospective study in Shenzhen and Hong Kong. Patients with COVID-19 infection were included. A systematic review of the published literature on radiologic features of COVID-19 infection was conducted. RESULTS: The predominant imaging pattern was of ground-glass opacification with occasional consolidation in the peripheries. Pleural effusions and lymphadenopathy were absent in all cases. Patients demonstrated evolution of the ground-glass opacities into consolidation and subsequent resolution of the airspace changes. Ground-glass and consolidative opacities visible on CT are sometimes undetectable on chest radiography, suggesting that CT is a more sensitive imaging modality for investigation. The systematic review identified four other studies confirming the findings of bilateral and peripheral ground glass with or without consolidation as the predominant finding at CT chest examinations. CONCLUSION: Pulmonary manifestation of COVID-19 infection is predominantly characterized by ground-glass opacification with occasional consolidation on CT. Radiographic findings in patients presenting in Shenzhen and Hong Kong are in keeping with four previous publications from other sites.© RSNA, 2020See editorial by Kay and Abbara in this issue.

Efficacy of gefitinib at reduced dose in EGFR mutant non-small cell lung carcinoma.

As a first-generation epidermal growth factor receptor-tyrosine kinase inhibitor, gefitinib was approved by the US Food and Drug Administration for treatment of advanced non-small cell carcinoma with sensitizing EGFR mutations. Gefitinib is known to have adverse effects, which may necessitate dose reduction or even change to alternative preparation of epidermal growth factor receptor-tyrosine kinase inhibitor. There has been concern on dose reduction resulting in reduced dose gefitinib, especially on its efficacy. This was a retrospective single-center cohort study conducted in Queen Mary Hospital in Hong Kong that included 159 Chinese patients with advanced adenocarcinoma of lung that carried sensitizing EGFR mutations and had received gefitinib as first-line treatment. Patients who had reduced dose at 250 mg alternate day were compared with those who were able to maintain on standard dose of gefitinib at 250 mg daily. The primary end-point was progression-free survival. Among the 159 patients, 17 (10.7 %) of them were on reduced dose gefitinib, 14 among the 17 patients (82.4%) because of hepatotoxicity, and 3 (17.6%) because of cutaneous side effects. Patients on reduced dose and standard dose of gefitinib have comparable median progression-free survival. Hazard ratio was 1.121 (95% confidence interval = 0. 655-1.917, P-value = 0.678) for the reduced dose group and 3.385 for the standard dose group (95% confidence interval = 2.181-5.255) respectively (P-value < 0.001). Dose reduction in gefitinib to 250 mg alternate day in response to adverse effects was not associated with inferior outcome for patients on first-line gefitinib for advanced non-small cell carcinoma. Dose reduction is a feasible option for patients who have significant adverse effects with gefitinib.

Respiratory arrest requiring resuscitation as a rare presentation of obstructive sleep apnoea and hypothyroidism.

A 79-year-old man, who had significant cardiovascular morbidities, presented with out-of-hospital respiratory arrest. He regained breathing after brief cardiopulmonary resuscitation by his paramedic son. After meticulous investigations, acute cardiovascular events and metabolic causes were ruled out while features of obstructive sleep apnoea were elicited. The findings on in-laboratory polysomnography were compatible with severe obstructive sleep apnoea, with unusually prolonged apnoea duration of up to 2.7 min which most likely accounts for the presentation as 'respiratory arrest'. Thyroid function test for investigation of his weight gain confirmed hypothyroidism. His symptoms improved gradually after positive airway pressure therapy with bi-level support and thyroxine replacement. On further evaluation, his hypothyroidism is believed to be a complication of long-term amiodarone exposure. The case highlights that the combination of obstructive sleep apnoea and hypothyroidism can lead to catastrophic manifestation and the unusually long apnoea could be a feature prompting further workup for possible hypothyroidism.

Pulmonary embolism developing after therapeutic drainage of malignant pleural effusions.

We reported three cases of pulmonary embolism which presented acutely and was confirmed shortly after therapeutic drainage of malignant pleural effusion. The temporal association may suggest that massive pleural effusion can be a risk factor for pulmonary embolism arising from venous thrombosis of lower limbs in patients with malignancies. This association can be related to the intra-thoracic pressure changes related to therapeutic pleural drainage. In case patient developed paradoxical dysnoea and hypoxemia after drainage of malignant pleural effusion, alternate cause such as pulmonary embolism should be considered.

Control of brain metastases with alectinib in anaplastic lymphoma kinase-rearranged lung cancer.

Brain metastasis from non-small cell lung cancer remains a challenge to physicians. It occurs in 30% of patients with advanced stage adenocarcinoma of lung and is often regarded as the ominous sign of disease progression and death. Alectinib is likely to be a promising agent, even after the failure of crizotinib and ceritinib, for patients with anaplastic lymphoma kinase (ALK) -driven non-small cell lung cancer with brain metastasis, resulting in a durable response for both intracranial and extra-cranial diseases.

Comparing approaches to the management of malignant pleural effusions.

INTRODUCTION: Management of symptomatic malignant pleural effusions is becoming more complex due to the range of treatment options, which include therapeutic thoracenteses, thoracoscopic talc pleurodesis, bedside pleurodesis with talc or other sclerosing agents via small-bore chest catheters, indwelling pleural catheters, surgery, or a combination of some of these procedures. Areas covered: Recent advances for the expanding range of treatment options in malignant pleural effusions are summarized, according to the best available evidence. Expert commentary: Selection of a treatment approach in malignant pleural effusions should take into account patient preferences and performance status, tumor type, predicted prognosis, presence of a non-expandable lung, and local experience or availability. The role of pleurodesis has decreased with the advent of indwelling pleural catheters, which provide a high degree of symptomatic relief on an outpatient basis and, therefore, are being positioned as a first choice therapy in many centers. Talc poudrage pleurodesis should probably be reserved for those situations in which pleural tumor invasion is discovered during diagnostic thoracoscopy. Ongoing randomized controlled trials will offer solid evidence on which of the available palliative approaches should be selected for each particular patient.

The Impact of Obstructive Sleep Apnea and Tobacco Smoking on Endothelial Function.

BACKGROUND: Endothelial dysfunction has been recognized to occur in the context of obstructive sleep apnea (OSA) or tobacco smoking. However, the deleterious effect on vascular function with concurrence of both conditions is largely unknown. OBJECTIVE: To investigate whether the concurrence of OSA and smoking poses an additive detriment to endothelial dysfunction. METHODS: Chinese men without a history of chronic medical illness were invited to complete a questionnaire including smoking pack-year exposure, polysomnography and peripheral arterial tonometry (PAT) for endothelial function. Serum 8-isoprostane, advanced oxidation protein products (AOPP) and monocyte chemo-attractant protein-1 (MCP-1) were measured. RESULTS: 114 men were successfully enrolled. PAT ratio, adjusted for age and body mass index, correlated inversely with overall severity of OSA: apnea-hypopnea index (AHI), r = -0.160 (p = 0.092); oxygen desaturation index, r = -0.214 (p = 0.024); duration of oxygen saturation <90%, r = -0.219 (p = 0.020); and minimum oxygen saturation, r = 0.250 (p = 0.008). The PAT ratio decreased with increasing pack-year group (p = 0.018). It was lower with concurrent smoking history and moderate-severe OSA (AHI ≥15/h) compared to having one or neither factor (p = 0.011). Serum levels of 8-isoprostane and AOPP were positively related to severity of OSA, while MCP-1 correlated with smoking quantity. Multiple linear regression analyses showed that severity of intermittent hypoxia, MCP-1 and pack-year exposure were independent predictors of PAT ratio. CONCLUSION: While OSA, in particular intermittent hypoxemia, and tobacco smoking were independent risk factors, the concurrence of moderate-severe OSA and smoking was associated with the most severe impairment in endothelial function.

Nicotinic acetylcholine receptor expression in human airway correlates with lung function.

Nicotine and its derivatives, by binding to nicotinic acetylcholine receptors (nAChRs) on bronchial epithelial cells, can regulate cellular signaling and inflammatory processes. Delineation of nAChR subtypes and their responses to nicotine stimulation in bronchial epithelium may provide information for therapeutic targeting in smoking-related inflammation in the airway. Expression of nAChR subunit genes in 60 bronchial epithelial biopsies and immunohistochemical staining for the subcellular locations of nAChR subunit expression were evaluated. Seven human bronchial epithelial cell lines (HBECs) were exposed to nicotine in vitro for their response in nAChR subunit gene expression to nicotine exposure and removal. The relative normalized amount of expression of nAChR α4, α5, and α7 and immunohistochemical staining intensity of nAChR α4, α5, and ß3 expression showed significant correlation with lung function parameters. Nicotine stimulation in HBECs resulted in transient increase in the levels of nAChR α5 and α6 but more sustained increase in nAChR α7 expression. nAChR expression in bronchial epithelium was found to correlate with lung function. Nicotine exposure in HBECs resulted in both short and longer term responses in nAChR subunit gene expression. These results gave insight into the potential of targeting nAChRs for therapy in smoking-related inflammation in the airway.

Treatment outcomes in elderly with advanced-stage non-small cell lung cancer.

PURPOSE: Lung cancer remains the top cause of cancer morbidity and mortality in the world. Although the identification of epidermal growth factor receptor (EGFR) gene mutations could predict efficacy of tyrosine kinase inhibitor (TKI), testing for predictive biomarkers are not always possible due to tissue availability. The overall therapeutic decision remains a clinical one for a significant proportion of elderly patients with advanced stage lung cancer but no known EGFR mutation status. The purpose of this study was to compare the outcome of drug treatment modalities in progression-free survival (PFS) and overall survival (OS) for elderly with advanced-stage non-small cell lung cancer (NSCLC) and to identify clinical parameters that could predict treatment outcome. METHODS: Clinical records of patients aged 70 years or older with advanced-stage NSCLC who have received treatment were reviewed. A group of gender- and histology-matched subjects younger than age 70 years were identified as controls. RESULTS: Fifty-six elderly patients were included. The median age at diagnosis was 73 years; 60.7 % received only one line of treatment. Baseline performance status (PS) was the only predictor of improved PFS (p = 0.042) and OS (p = 0.002). There was no difference in survival between the upfront chemotherapy and the TKI groups CONCLUSIONS: In elderly with advanced-stage NSCLC without known EGFR mutation status, use of EGFR-TKI and chemotherapy resulted in comparable survival benefits. Age was not predictive of worse treatment outcome. The baseline PS should be taken into consideration in the therapeutic decision in elderly with NSCLC where the EGFR mutation status is not known.