SARS appears to be infectious in origin. Fever followed by rapidly progressive respiratory compromise is the key complex of signs and symptoms from which the syndrome derives its name. The microbiologic origins of SARS remain unclear.

Epidemiological studies have implicated obstructive sleep apnea (OSA) as an independent comorbid factor in cardiovascular and cerebrovascular diseases. It is postulated that recurrent episodes of occlusion of upper airways during sleep result in pathophysiological changes that may predispose to vascular diseases. Insulin resistance is a known risk factor for atherosclerosis, and we postulate that OSA represents a stress that promotes insulin resistance, hence atherogenesis. This study investigated the relationship between sleep-disordered breathing and insulin resistance, indicated by fasting serum insulin level and insulin resistance index based on the homeostasis model assessment method (HOMA-IR). A total of 270 consecutive subjects (197 male) who were referred for polysomnography and who did not have known diabetes mellitus were included, and 185 were documented to have OSA defined as an apnea-hypopnea index (AHI) > or =5. OSA subjects were more insulin resistant, as indicated by higher levels of fasting serum insulin (p = 0.001) and HOMA-IR (p < 0.001); they were also older and more obese. Stepwise multiple linear regression analysis showed that obesity was the major determinant of insulin resistance but sleep-disordered breathing parameters (AHI and minimum oxygen saturation) were also independent determinants of insulin resistance (fasting insulin: AHI, p = 0.02, minimum O(2), p = 0.041; HOMA-IR: AHI, p = 0.044, minimum O(2), p = 0.022); this association between OSA and insulin resistance was seen in both obese and nonobese subjects. Each additional apnea or hypopnea per sleep hour increased the fasting insulin level and HOMA-IR by about 0.5%. Further analysis of the relationship of insulin resistance and hypertension confirmed that insulin resistance was a significant factor for hypertension in this cohort. Our findings suggest that OSA is independently associated with insulin resistance, and its role in the atherogenic potential of sleep disordered breathing is worthy of further exploration.

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Epidemiological studies have implicated obstructive sleep apnea (OSA) as an independent comorbid factor in cardiovascular and cerebrovascular diseases. The recurrent episodes of occlusion of upper airways during sleep result in pathophysiological changes that may predispose to vascular diseases, and we postulate that nitric oxide may be one of the mediators involved. This study investigates the levels of circulating nitric oxide (NO), measured as serum nitrites and nitrates, in the early morning in OSA subjects compared with control subjects, and the effect of overnight nasal continuous positive airway pressure (nCPAP) in OSA subjects. Thirty men with moderate to severe OSA (age = 41.9 +/- 9.0; apnea-hypopnea index, AHI = 48.0 +/- 18.1) were compared with 40 healthy men (age = 40.6 +/- 5.4; AHI = 1.4 +/- 1.2). Serum nitrite/nitrate levels were significantly lower in OSA subjects (OSA = 38.9 +/- 22.9 microM, control subjects = 63.1 +/- 47.5 microM, p = 0.015). There was significant negative correlation between serum nitrites/nitrates and the following parameters: AHI (r = -0.389, p = 0.001), oxygen desaturation time (r = -0.346, p = 0.004), and systolic blood pressure (BP) (r = -0.335, p = 0.005). Stepwise multiple linear regression with systolic or diastolic BP as the dependent variable identified serum nitrites/nitrates as the only significant correlate. Twenty-two OSA subjects had measurements of serum NO at baseline and after an overnight application nCPAP. There was significant increase in serum NO after nCPAP (baseline = 30.5 +/- 14.4 microM, after nCPAP = 81.0 +/- 82.1 microM, p = 0.01). This study demonstrates, for the first time, that circulating NO is suppressed in OSA, and this is promptly reversible with the use of nCPAP. The findings offer support for nitric oxide being one of the mediators involved in the acute hemodynamic regulation and long-term vascular remodeling in OSA.

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Severe acute respiratory syndrome (SARS) is associated with considerable morbidity and mortality in the acute phase. Worldwide case fatality rate is 11% (range 7 to 27%) for the most severely affected regions. Several adverse prognostic factors have been identified, including advanced age, presence of comorbidity, higher lactose dehydrogenase levels and initial neutrophil count, but the impact of viral and other host factors on outcome is unknown. Published data on sequelae of SARS are limited. Clinical follow-up of patients who recovered from SARS has demonstrated radiological, functional and psychological abnormalities of varying degrees. In the early rehabilitation phase, many complained of limitations in physical function from general weakness and/or shortness of breath. In a small series of subjects who underwent CT scan of the chest, over half showed some patchy changes consistent with pulmonary fibrosis. Lung function testing at 6-8 weeks after hospital discharge showed mild or moderate restrictive pattern consistent with muscle weakness in 6-20% of subjects. Mild decrease in carbon monoxide diffusing capacity was detected in a minority of subjects. Preliminary evidence suggests that these lung function abnormalities will improve over time. Psychobehavioural problems of anxiety and/or depression were not uncommon in the early recovery phase, and improved over time in the majority of patients. Avascular necrosis of the hip has been reported as another complication. The long-term sequelae of SARS are still largely unknown. It is important to follow up these patients to detect and appropriately manage any persistent or emerging long-term sequelae in the physical, psychological and social domains.

Transplantation of mesenchymal stem cells (MSCs) holds great promise in the repair of cigarette smoke (CS)-induced lung damage in chronic obstructive pulmonary disease (COPD). Because CS leads to mitochondrial dysfunction, we aimed to investigate the potential benefit of mitochondrial transfer from human-induced pluripotent stem cell-derived MSCs (iPSC-MSCs) to CS-exposed airway epithelial cells in vitro and in vivo. Rats were exposed to 4% CS for 1 hour daily for 56 days. At Days 29 and, human iPSC-MSCs or adult bone marrow-derived MSCs (BM-MSCs) were administered intravenously to CS-exposed rats. CS-exposed rats exhibited severe alveolar destruction with a higher mean linear intercept (Lm) than sham air-exposed rats (P < 0.001) that was attenuated in the presence of iPSC-MSCs or BM-MSCs (P < 0.01). The attenuation of Lm value and the severity of fibrosis was greater in the iPSC-MSC-treated group than in the BM-MSC-treated group (P < 0.05). This might have contributed to the novel observation of mitochondrial transfer from MSCs to rat airway epithelial cells in lung sections exposed to CS. In vitro studies further revealed that transfer of mitochondria from iPSC-MSCs to bronchial epithelial cells (BEAS-2B) was more effective than from BM-MSCs, with preservation of adenosine triphosphate contents. This distinct mitochondrial transfer occurred via the formation of tunneling nanotubes. Inhibition of tunneling nanotube formation blocked mitochondrial transfer. Our findings indicate a higher mitochondrial transfer capacity of iPSC-MSCs than BM-MSCs to rescue CS-induced mitochondrial damage. iPSC-MSCs may thus hold promise for the development of cell therapy in COPD.

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.