Introduction: COPD is a worldwide public health issue, while anxiety and depression are highly prevalent comorbidities in COPD, some reviews in overseas reported prevalence rates of up to 75% for anxiety and up to 80% for depression among COPD patients. The situation in Hong Kong is largely unclear and information is lacking. Objective: To assess the prevalence of anxiety and depression in a regional hospital in Hong Kong and to evaluate the odds ratio of different stages of severity in COPD. Method: COPD patients before hospital discharge from E3 ward in Princess Margaret Hospital (in-patient) and COPD patients who attend out-patient clinic in block K7 in PMH (out-patient) will be asked for consent to participate in the study. Baseline demographic and clinical information includes staging of COPD, questionnaires of HADS, MMRC, CAT score will be collected by research nurses after consent is obtained. Result: A total of 260 patients have been approached, with a response rate of 58.08%. 75 in-patients and 76 out-patients were eligible for the study. Our study showed the overall prevalence of depression and anxiety among COPD population are 61.6% and 23.2% respectively. Odds Ratio of depression and anxiety were increased when severity of COPD increased from stage I to IV. Compared with stage I COPD patients, the respective crude odds ratio of depression for stage II is 1.25 (95% CI: 0.15-10.23), stage III is 1.44 (95% CI: 0.19-10.89), while stage IV is 2.09 (95% CI: 0.26-16.86); But in anxiety, the value is insignificant as the odds ratio is less than 1. Conclusion: This is the first study in Hong Kong which is targeted on estimating the prevalence of depression and anxiety among COPD population and to correlate the finding with the COPD severity. Depression and anxiety are prevalent among the COPD patients as suggested in the study. The possibility of depression increased when severity of COPD stage increases, but the result in anxiety cannot be confirmed. No specific risk factors were found to have statistical significant association with the presence of depression and anxiety, but the current study still warrant attention. Further large scale study may be needed to reveal the situation. A more comprehensive and holistic approach to the COPD patients should be employed to tackle their special need during disease progress, in order to reduce the whole health care system burden. / published_or_final_version / Public Health / Master / Master of Public Health

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by persistent airway obstruction that is only partially reversible. It is the fourth leading cause of death and is predicted to be the third by 2030. The progression of the disease involves chronic inflammation, oxidative stress, excess protease activity, increased lung cell apoptosis and accelerated lung aging, but the exact pathogenesis is still unclear. The major cause of COPD is cigarette smoking(CS). Although COPD is associated with increasing social and economical burden, there have been few advances in pharmacological therapy of COPD. Mesenchymal stem cells (MSCs) are fibroblast-like multipotent stem cells which can be isolated from a broad range of sources including bone marrow (BM) and adipose tissue. Administration of BM-derivedMSCs (BM-MSC) or adipose tissue-derived MSCs was reported to attenuate CS-induced emphysema in murine models. Induced pluripotent stem cell-derived MSC (IPSC-MSC) are MSCs differentiated from induced pluripotent stem cells(IPSCs), which are pluripotent cells generated by somatic cell reprogramming in vitro. IPSC-MSCs have several advantages over BM-MSC, including more abundant sources and high capacity of doubling without loss of differentiation potency. A general exploration and comparison on the effects of human IPSC-MSC and BM-MSC treatments were carried out in a 56-day CS-exposed rat model. Compared to BM-MSC, IPSC-MSC showed a higher capacity to reside in lung tissue. The two treatments shared similar efficacy to attenuate CS-induced lung cell apoptosis, to restore CS-induced reduction of lungIL-10and to alleviate CS-induced elevation of systemic TGF-β1. In addition, IPSC-MSC was found to cause reduction in CS-induced elevation of systemic oxidative stress and reversal of CS-induced reduction of lung adiponectin. Furthermore, in order to understand the possible paracrine mechanism involved, human airway epithelial cells were treated with IPSC-MSC or BM-MSC-conditioned medium in a cell culture system in the presence of cigarette smoke medium (CSM). Potentiation rather than attenuation of CSM-induced release of pro-inflammatory cytokine IL-8, MCP-1 and IL-6 was observed with IPSC-MSC or BM-MSC conditioned medium. It is currently unknown whether cultured IPSC-MSCs or BM-MSCs will release pro-inflammatory mediators into the conditioned medium or not. In order to study CS-induced oxidative stress and inflammation in a short time frame, anacute (5-day) CS-exposed rat model was established in juvenile and adult groups. An age-dependent alteration of CS-induced oxidative and inflammatory responses was demonstrated in this model. In summary, our in vivo rat model provides a platform for elucidating the effects of stem cell treatment in CS-induced oxidative stress and inflammation, leading to lung damage. Our findings suggest that treatment of IPSC-MSC or BM-MSC might be able to slow down CS-induced disease progression, possibly through anti-oxidant, anti-inflammatory and anti-apoptotic properties. However, caution should be taken as our in vitro data revealed that conditioned medium from MSCs may provoke pro-inflammatory responses. Further studies on the regulation of the activity of MSCs in vivo will be needed before developing IPSC-MSC into cell therapies for COPD to halt the progression over time. / published_or_final_version / Medicine / Master / Master of Philosophy

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Gerontology / Master / Master of Social Sciences

No description available.

No description available.

There is evidence that non-surgical treatment of OSA improves blood pressure (BP) in patients with obstructive sleep apnea (OSA). The objective of this study is to determine the effect of maxillomandibular advancement (MMA) surgery for OSA on BP. 15 patients undergoing MMA surgery for treatment of OSA were enrolled. Ambulatory BP, and BMI were recorded pre- and post-operatively. The average age of the patients was 48.9 years and they had mean preoperative AHI of 40.8 and a mean baseline BMI of 30.8 kg/m2. There were no statistically significant reductions in mean systolic or diastolic BP postoperatively. The BMI was found to decrease on average from 30.8 kg/m2 to 29.3 kg/m2 at follow up (p = 0.01). There were no identifiable relationships between OSA severity and BP. Given the prevalence of OSA and it’s adverse medical consequences, more studies to determine the effect of MMA on BP are warranted.

No description available.

Weight loss and depletion of fat-free mass commonly occurs in patients with COPD. The objective of the study was to determine the magnitude and duration of protein depletion during an episode of acute exacerbation. Fifteen patients (9 women and 6 men) admitted for an acute exacerbation of COPD participated in a descriptive study that prospectively measured individual nitrogen balance over a 6-week follow-up period using repeated nitrogen balance tests. / The mean nitrogen balance in hospital was -13.20 +/- 11.63 g N/day. Only 2 patients achieved a positive nitrogen balance by 2 weeks post-admission and 4 more patients by 4 weeks post-admission. At 6-weeks post-admission, 7 patients (47%) were still in negative nitrogen balance (-10.75 +/- 9.34 g N/day). Protein and energy intakes were significantly higher in patients who achieved a positive nitrogen balance (1.7 +/- 0.5 g protein/kg/day and 120 +/- 30% of estimated energy expenditure (1.7 x REE)) than patients who remained in a negative nitrogen balance (1.3 +/- 0.6 g protein/kg/day and 70 +/- 20% of estimated energy expenditure). There were no significant changes in weight or handgrip strength over the follow-up period. No effect of cumulative or daily corticosteroid doses on nitrogen balance or changes in handgrip strength were found. / In conclusion, the catabolic stress of an acute exacerbation on nutritional status is remarkable. Patients admitted for an acute exacerbation of COPD are in severe negative nitrogen balance, which improves very slowly post-discharge. A negative nitrogen balance is prolonged in patients who have a decreased protein and energy intake.

Obstructive sleep apnoea (OSA) is a common condition characterized by recurrent complete and partial upper airway obstruction. OSA sufferers have been shown to have a significantly smaller upper airway lumen compared to non-OSA sufferers. However, non-anatomical factors of sleep stage, arousability and neuromechanical responses to airway occlusion and chemosensitivity are likely to play a significant part in influencing OSA severity across the night. An exploration of these non-anatomical factors forms the basis for the experiments in this thesis. In the first experimental chapter presented in this thesis, a detailed retrospective epoch by epoch analysis of nocturnal polysomnography in 253 patients referred to a clinical sleep service was performed to examine differences in sleep apnoea severity and arousal indices across the different stages of sleep, while controlling for posture. Both patients with and without OSA demonstrated significant reductions in respiratory and arousal event frequencies from stage 1 to 4 with intermediate frequencies in REM sleep. Lateral posture was also associated with significant improvements in OSA and arousal frequencies, with an effect size comparable to that of sleep stage. The majority of patients showed significant reductions in OSA severity during slow wave sleep. In non-REM sleep, there was a strong correlation between OSA severity and arousal frequency. These results confirm in a large group of patients, a strong sleep stage dependence of both OSA and arousal frequencies. The second study in this thesis explores the development of a CO2 stabilising or ‘clamp’ device to enable the provision of positive airway pressure, and by proportional rebreathing, the maintenance of relatively constant end-tidal CO2 despite significant hyperventilation. Healthy volunteers performed brief periods of significant voluntary hyperventilation at 2 levels of CPAP with the rebreathing function off and with active CO2 clamping in randomized order. Compared to CPAP alone, the device substantially attenuated hypocapnia associated with hyperventilation. The third study of the thesis was designed to investigate if increasing and stabilizing end-tidal CO2 could improve obstructive breathing patterns during sleep. 10 patients with severe OSA underwent rapid CPAP dialdown from therapeutic to a sub-therapeutic level to experimentally induce acute, partial upper airway obstruction over 2 minute periods repeated throughout the night. The CO2 clamp device developed and validated in Study 2 was used to determine whether during periods of partial upper airway obstruction with severe flow limitation, (1) increased end-tidal CO2 resulted in improved airflow and ventilation and (2) clamping end-tidal CO2 lessened post-arousal ventilatory undershoot. Three conditions were studied in random order: no clamping of CO2, clamping of end-tidal CO2 3-4 mmHg above eucapnic levels during the pre-dialdown baseline period only, and clamping of CO2 above eucapnia during both baseline and dialdown periods. Elevated CO2 in the baseline period alone or in the baseline and dialdown periods together resulted in significantly higher peak inspiratory flows and ventilation compared to the no clamp condition. Breath-by-breath analysis immediately pre- and post-arousal showed higher end-tidal CO2 despite hyperventilation immediately post-arousal and attenuation of ventilatory undershoot in CO2 versus non-CO2 clamped conditions. These results support that modulation of ventilatory drive by changes in pre- and post-arousal CO2 are likely to importantly influence upper airway and ventilatory stability in OSA. The fourth study was designed to explore several possible pathophysiological mechanisms whereby obstructive sleep apnoea is improved in stages 3 & 4 (slow wave) versus stage 2 sleep. 10 patients with severe OSA who demonstrated significant reductions in OSA frequency during slow wave sleep on diagnostic investigation were studied. Patients underwent rapid dialdowns from therapeutic CPAP to 3 different pre-determined sub-therapeutic pressures to induce partial airway obstruction and complete airway occlusions in a randomised sequence during the night in both stage 2 and slow wave sleep. Partial airway obstructions and complete occlusions were maintained until arousal occurred or until 2 minutes had elapsed, whichever came first. After airway occlusions, time to arousal, peak pre-arousal negative epiglottic pressure and the rate of ventilatory drive augmentation were significantly greater, suggesting a higher arousal threshold and ventilatory responsiveness to respiratory stimuli during slow wave compared to stage 2 sleep. Post dialdowns, the likelihood of arousal was lower with less severe dialdowns and in slow wave compared to stage 2 sleep. Respiratory drive measured by epiglottic pressure progressively increased post-dialdown, but did not translate into increases in peak flow or ventilation pre-arousal and was not different between sleep stages. These data suggest that while arousal time and propensity following respiratory challenge are altered by sleep depth, there is little evidence to support that upper airway and ventilatory compensation responses to respiratory load are fundamentally improved in slow wave compared to stage 2 sleep. In summary, sleep stage, arousal threshold and chemical drive appear to strongly influence upper airway and ventilatory stability in OSA and are suggestive of important non-anatomical pathogenic mechanisms in OSA.