Loretta Y. C. Yam

Development of a standard treatment protocol for severe acute respiratory syndrome

Summary A series of 31 patients with probable SARS, diagnosed from WHO criteria, were treated according to a treatment protocol consisting of antibacterials and a combination of ribavirin and methylprednisolone. Through experience with the first 11 patients, we were able to finalise standard dose regimens, including pulsed methylprednisolone. One patient recovered on antibacterial treatment alone, 17 showed rapid and sustained responses, and 13 achieved improvement with step-up or pulsed methylprednisolone. Four patients required short periods of non-invasive ventilation. No patient required intubation or mechanical ventilation. There was no mortality or treatment morbidity in this series.

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.

Detection of SARS Coronavirus in Patients with Suspected SARS

Cases of severe acute respiratory syndrome (SARS) were investigated for SARS coronavirus (SARS-CoV) through RNA tests, serologic response, and viral culture. Of 537 specimens from patients in whom SARS was clinically diagnosed, 332 (60%) had SARS-CoV RNA in one or more clinical specimens, compared with 1 (0.3%) of 332 samples from controls. Of 417 patients with clinical SARS from whom paired serum samples were available, 92% had an antibody response. Rates of viral RNA positivity increased progressively and peaked at day 11 after onset of illness. Although viral RNA remained detectable in respiratory secretions and stool and urine specimens for >30 days in some patients, virus could not be cultured after week 3 of illness. Nasopharyngeal aspirates, throat swabs, or sputum samples were the most useful clinical specimens in the first 5 days of illness, but later in the illness viral RNA could be detected more readily in stool specimens.

Effectiveness of Noninvasive Positive Pressure Ventilation in the Treatment of Acute Respiratory Failure in Severe Acute Respiratory Syndrome

Objectives: To study the effectiveness of noninvasive positive pressure ventilation (NIPPV) in the treatment of acute respiratory failure (ARF) in severe acute respiratory syndrome (SARS), and the associated infection risk. Methods: All patients with the diagnosis of probable SARS admitted to a regional hospital in Hong Kong from March 9 to April 28, 2003, and who had SARS-related respiratory distress complications were recruited for NIPPV usage. The health status of all health-care workers working in the NIPPV wards was closely monitored, and consent was obtained to check serum for coronavirus serology. Patient outcomes and the risk of SARS transmission to health-care workers were assessed. Results: NIPPV was applied to 20 patients (11 male patients) with ARF secondary to SARS. Mean age was 51.4 years, and mean acute physiology and chronic health evaluation II score was 5.35. Coronavirus serology was positive in 95% (19 of 20 patients). NIPPV was started 9.6 days (mean) from symptom onset, and mean duration of NIPPV usage was 84.3 h. Endotracheal intubation was avoided in 14 patients (70%), in whom the length of ICU stay was shorter (3.1 days vs 21.3 days, p < 0.001) and the chest radiography score within 24 h of NIPPV was lower (15.1 vs 22.5, p = 0.005) compared to intubated patients. Intubation avoidance was predicted by a marked reduction in respiratory rate (9.2 breaths/min) and supplemental oxygen requirement (3.1 L/min) within 24 h of NIPPV. Complications were few and reversible. There were no infections among the 105 health-care workers caring for the patients receiving NIPPV. Conclusions: NIPPV was effective in the treatment of ARF in the patients with SARS studied, and its use was safe for health-care workers.

Inability of physicians to use metered-dose inhalers.

The effectiveness of antiasthmatic therapy with metered-dose inhalers (MDIs) is usually limited by defective inhalational technique. This study surveyed the MDI inhalation performance and knowledge of 100 physicians whose performance (demarcated into six stages) and knowledge scores correlated (r = 0.33, p < 0.001). Inhalation performance scores for shaking the canister, full expiration prior to using the MDI, breath holding thereafter, and positioning of the mouth-piece correlated with their corresponding knowledge scores (p < or = 0.02). Training of physicians entailing actual instruction and supervision of inhalational maneuvers may enhance the ability of doctors to use MDIs and facilitate better patient supervision.

The burden of lung disease in Hong Kong: A report from the Hong Kong Thoracic Society

Background and objective:  The burden of lung disease in Hong Kong is not known. This study determined the mortality and hospitalization rates of respiratory diseases in Hong Kong in 2005, their trend in the past decade and their incidence/prevalence.

CD209 (DC-SIGN) -336A>G promoter polymorphism and severe acute respiratory syndrome in Hong Kong Chinese

Abstract CD209 (DC-SIGN) is an important C-type lectin which acts a receptor of many pathogens. The single nucleotide polymorphism (SNP) −336A>G in the CD209 promoter has been demonstrated to regulate promoter activity and to be associated with several important infectious diseases, such as human immunodeficiency virus–1 (HIV-1), Mycobacterium tuberculosis, and Dengue fever. CD209 facilitates severe acute respiratory syndrome (SARS)–coronavirus spike protein-bearing pseudotype driven infection of permissive cells in vitro. In keeping with previously published findings, our in vitro studies confirmed that this SNP modulates gene promoter activity. Genetic association analysis of this SNP with clinico-pathologic outcomes in 824 serologic confirmed SARS patients showed that the −336AG/GG genotype SARS patients was associated with lower standardized lactate-dehydrogenase (LDH) levels compared with the −336AA patients (p = 0.014, odds ratio = 0.40). High LDH levels are known to be an independent predictor for poor clinical outcome, probably related to tissue destruction from immune hyperactivity. Hence, SARS patients with the CD209 −336 AA genotype carry a 60% chance of having a poorer prognosis. This association is in keeping with the role of CD209 in modulating immune response to viral infection. The relevance of these findings for other infectious diseases and inflammatory conditions would be worth investigating.

Association of ICAM3 Genetic Variant with Severe Acute Respiratory Syndrome

Abstract Genetic polymorphisms have been demonstrated to be associated with vulnerability to human infection. ICAM3, an intercellular adhesion molecule important for T cell activation, and FCER2 (CD23), an immune response gene, both located on chromosome 19p13.3 were investigated for host genetic susceptibility and association with clinical outcome. A case-control study based on 817 patients with confirmed severe acute respiratory syndrome (SARS), 307 health care worker control subjects, 290 outpatient control subjects, and 309 household control subjects unaffected by SARS from Hong Kong was conducted to test for genetic association. No significant association to susceptibility to SARS-CoV infection was found for the FCER2 and the ICAM3 single nucleotide polymorphisms. However, patients with SARS homozygous for ICAM3 Gly143 showed significant association with higher lactate dehydrogenase levels (P=.0067; odds ratio [OR], 4.31 [95% confidence interval [CI], 1.37–13.56]) and lower total white blood cell counts (P=.022; OR, 0.30 [95% CI, 0.10–0.89]) on admission. These findings support the role of ICAM3 in the immunopathogenesis of SARS.

SARS: ventilatory and intensive care

Severe acute respiratory syndrome (SARS) is an emerging infection caused by a novel coronavirus. It is characterised by a highly infectious syndrome of fever and respiratory symptoms, and is usually associated with bilateral lung infiltrates. The clinical syndrome of SARS often progresses to varying degrees of respiratory failure, with about 20% of patients requiring intensive care. Despite concern about potential aerosol generation, non‐invasive ventilation (NIV) has been reported to be efficacious in the treatment of SARS‐related ARF without posing infection risks to health care workers (HCW). Spontaneous pneumomediastinum and pneumothorax in SARS is common. The incidence of NIV‐associated barotrauma ranged from 6.6% to 15%. Patients who fail to tolerate NIV or fail NIV with progressive dyspnoea, tachypnoea and hypoxaemia should be intubated and mechanically ventilated. Mortality rates in intensive care units for SARS patients were high: 34–53% at 28 days, when some patients were still being ventilated. Strict adherence to infection control measures including isolation, use of appropriate personal protective equipment and negative pressure environment had been reported to eliminate cross‐infection to HCW.

Low prevalence of subclinical severe acute respiratory syndrome-associated coronavirus infection among hospital healthcare workers in Hong Kong

We recruited 688 hospital healthcare workers who cared for patients with severe acute respiratory syndrome (SARS) and did not develop the disease in the Hong Kong outbreak in 2003. A questionnaire survey was conducted and serum samples were collected for SARS-associated coronavirus (SARS-CoV) antibody. The high-risk procedures performed and the types of unprotected exposures were recorded for analysis. Only 1 asymptomatic nurse had positive serological test. The result demonstrates the low rate of subclinical SARS-CoV infection in hospital healthcare workers and that the infection control practice against SARS in Hong Kongs hospitals during the outbreak was highly effective.