Randomised study of three non-surgical treatments in mild to moderate obstructive sleep apnoea

Background: Patients with mild to moderate obstructive sleep apnoea (OSA) may be managed with different treatment options. This study compared the effectiveness of three commonly used non-surgical treatment modalities. Methods: Subjects with mild to moderate OSA were randomised to one of three treatment groups for 10 weeks: conservative measures (sleep hygiene) only, continuous positive airways pressure (CPAP) in addition to conservative measures or an oral appliance in addition to conservative measures. All overweight subjects were referred to a weight-reduction class. OSA was assessed by polysomnography. Blood pressure was recorded in the morning and evening in the sleep laboratory. Daytime sleepiness was assessed with the Epworth Sleepiness Scale. Health-related quality of life (HRQOL) was assessed with the 36-Item Short-Form Health Survey (SF-36) and Sleep Apnoea Quality of Life Index (SAQLI). Results: 101 subjects with a mean (SEM) apnoea-hypopnoea index (AHI) of 21.4 (1.1) were randomised to one of the three groups. The severity of sleep-disordered breathing was decreased in the CPAP and oral appliance groups compared with the conservative measures group, and the CPAP group was significantly better than the oral appliance group. Relief from sleepiness was significantly better in the CPAP group. CPAP was also better than the oral appliance or conservative measures in improving the "bodily pain" domain, and better than conservative measures in improving the "physical function" domain of SF-36. Both CPAP and the oral appliance were more effective than conservative measures in improving the SAQLI, although no difference was detected between the CPAP and oral appliance groups. CPAP and the oral appliance significantly lowered the morning diastolic blood pressure compared with baseline values, but there was no difference in the changes in blood pressure between the groups. There was also a linear relationship between the changes in AHI and body weight. Conclusion: CPAP produced the best improvement in terms of physiological, symptomatic and HRQOL measures, while the oral appliance was slightly less effective. Weight loss, if achieved, resulted in an improvement in sleep parameters, but weight control alone was not uniformly effective.published_or_final_versio

Prevalence of allergic rhinitis and its associated morbidity in adults with asthma: A multicentre study

Objectives To assess the prevalence of allergic rhinitis in adult patients with asthma in Hong Kong, and to compare the morbidity endured by asthma patients with and without allergic rhinitis. Design Cross-sectional study. Setting Respiratory clinics of four major public hospitals in Hong Kong. Patients A total of 600 adults with asthma were recruited from March to May 2007. Main outcome measures Doctors and patients completed separate questionnaires evaluating symptoms, treatment, and health care utilisation. Spirometry data were obtained for a subgroup of patients at the time of survey completion. Results The patients consisted of 267 males and 333 females, with 251 having spirometry data. The mean pre-bronchodilator 1-second forced expiratory volume predicted among those who had spirometry performed was 88% (standard deviation, 28%). In all, 50% of the patients had intermittent and 50% had persistent asthma. Over three quarters (463/600; 77%) of patients had experienced allergic rhinitis symptoms in the past 12 months, of whom 96% had a previous diagnosis of allergic rhinitis. Asthmatics without allergic rhinitis symptoms had higher rates of visits to doctors, pharmacy visits, emergency department attendances, and hospitalisations for asthma than those with both conditions. Among subjects with asthma and allergic rhinitis, those taking nasal steroid (226/463; 49%) had lower rates of emergency department visits (13 vs 25%, P=0.002) and hospitalisations (7 vs 13%, P=0.045) for asthma than those who were not. Conclusion Allergic rhinitis is a common co-morbid condition of asthma in this hospital clinic cohort. Treatment of allergic rhinitis with intra-nasal steroid was associated with less health care utilisation for asthma.published_or_final_versio

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 β3 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.postprin

Using Polyanionic Heparin Mimetics for the treatment of COPD

Poster Presentation - Theme 1: Cell biologyCOPD patients suffer from sustained inflammation leading to airway damage and deteriorating lung function caused by unopposed protease activity resulting from a1-antitrypsin resistant supramolecular complexes of neutrophil elastase and shed syndecan-1 in the airway. It was further shown that the action of the GAG digesting enzyme heparanase facilitates syndecan-1 shedding ...postprin

Myasthenic crisis in patients with generalised myasthenia gravis

INTRODUCTION: Myasthenia gravis (MG) is an important autoimmune disease causing generalised weakness and even mortality, which is amenable to immunotherapies. Myasthenic crisis (MC) is the most serious presentation of MG typically requiring ventilator support under the care of intensive care unit. We studied factors which predict development of MC in generalised MG (gMG) patients and patients’ serum cytokine levels as potential biomarkers for MG exacerbation and crisis ...published_or_final_versio

Inflammatory Endotype-Associated Airway Resistome in Chronic Obstructive Pulmonary Disease.

Antimicrobial resistance is a global concern in chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD). The collection of antibiotic resistance genes or resistome in human airways may underlie the resistance. COPD is heterogeneous, and understanding the airway resistome in relation to patient phenotype and endotype may inform precision antibiotic therapy. Here, we characterized the airway resistome for 94 COPD participants at stable disease. Among all demographic and clinical factors, patient inflammatory endotype was associated with the airway resistome. There were distinct resistome profiles between patients with neutrophilic or eosinophilic inflammation, two primary inflammatory endotypes in COPD. For neutrophil-predominant COPD, the resistome was dominated by multidrug resistance genes. For eosinophil-predominant COPD, the resistome was diverse, with an increased portion of patients showing a macrolide-high resistome. The differential antimicrobial resistance pattern was validated by sputum culture and in vitro antimicrobial susceptibility testing. Ralstonia and Pseudomonas were the top contributors to the neutrophil-associated resistome, whereas Campylobacter and Aggregatibacter contributed most to the eosinophil-associated resistome. Multiomic analyses revealed specific host pathways and inflammatory mediators associated with the resistome. The arachidonic acid metabolic pathway and matrix metallopeptidase 8 (MMP-8) exhibited the strongest associations with the neutrophil-associated resistome, whereas the eosinophil chemotaxis pathway and interleukin-13 (IL-13) showed the greatest associations with the eosinophil-associated resistome. These results highlight a previously unrecognized link between inflammation and the airway resistome and suggest the need for considering patient inflammatory subtype in decision-making about antibiotic use in COPD and broader chronic respiratory diseases. IMPORTANCE Antibiotics are commonly prescribed for both acute and long-term prophylactic treatment in chronic airway disorders, such as chronic obstructive pulmonary disease (COPD), and the rapid growth of antibiotic resistance is alarming globally. The airway harbors a diverse collection of microorganisms known as microbiota, which serve as a reservoir for antibiotic resistance genes or the resistome. A comprehensive understanding of the airway resistome in relation to patient clinical and biological factors may help inform decisions to select appropriate antibiotics for clinical therapies. By deep multiomic profiling and in vitro phenotypic testing, we showed that inflammatory endotype, the underlying pattern of airway inflammation, was most strongly associated with the airway resistome in COPD patients. There were distinct resistome profiles between neutrophil-predominant and eosinophil-predominant COPD that were associated with different bacterial species, host pathways, and inflammatory markers, highlighting the need of considering patient inflammatory status in COPD antibiotic management

Molecular signatures of in vitro drug response in lung cancer

Poster Presentations - Molecular Classification of Tumors and Novel Biomarkers: abstract no. 5589This journal suppl. entitled : Proceedings: AACR 104th Annual Meeting 2013 ...We are developing in vitro drug response signatures based on profiling of mRNA (Illumina WG6-V3 arrays), DNA mutation (COSMIC and deep sequencing), DNA copy number (Illumina Human1M-Duov3 SNP array) and DNA methylation (Illumina HumanMethylation450) from lung cancer cell lines to predict which drugs a patient's tumor is most likely to respond to. We have generated drug response phenotypes (MTS colorimetric assays) for 25 standard, targeted, and new chemotherapy agents and combinations for 100 ...postprin

Recent advances in treatment of advanced stage non-small cell lung cancer

Co-Organized by University of Hong Kong Queen Mary Hospital; Peking University First Hospital; and Union Hospital Fujian Medical Universit