Polymorphisms in the IL-4, IL-4 receptor alpha chain, TNF-alpha, and lymphotoxin-alpha genes and risk of asthma in Hong Kong Chinese adults.

BACKGROUND: Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components. However, association studies with interleukin-4 (IL-4), IL-4 receptor alpha subunit (IL-4R alpha), tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin-alpha (LT-alpha) genes were inconclusive, as both positive and negative results were obtained in several populations studied. We aimed to investigate the association of the polymorphisms for IL-4 (C-589T), IL-4R alpha (Gln576Arg), TNF-alpha (G-308A) and LT-alpha (A252G) genes as candidates and asthma in adult Hong Kong Chinese population. METHODS: The association study was conducted in an age- and smoking status-matched case-control design in asthma patients (n = 292) and healthy controls (n = 292) using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: No significant differences were found in allele and genotype frequencies of all four genes between patients and controls. After stratification by atopic status, the heterozygous AG genotype of LT-alpha (A252G) was found to increase risk of asthma in atopic population [odds ratio (OR) = 2.00, 95% CI 1.09-3.67, p = 0.024]. When stratified by smoking status, we found increased risk of asthma with subjects carrying the heterozygous AG and homozygous GG genotypes of LT-alpha in ever-smokers (OR = 2.73, 95% CI 1.11-6.69, p = 0.028 for heterozygotes; OR = 3.34, 95% CI 1.16-9.62, p = 0.026 for homozygotes). CONCLUSION: Our results suggest that the variability of LT-alpha genotypes may have potential implications for individual susceptibility to asthma in atopic or in ever-smoking Chinese adults in Hong Kong.

Stress and psychological impact on SARS patients during the outbreak.

OBJECTIVE: To examine stress and psychological impact in severe acute respiratory syndrome (SARS) patients during the 2003 outbreak. SARS is a novel, highly infectious pneumonia, and its psychological impact is still unclear. METHOD: At the peak of the outbreak, SARS patients (n = 79) and healthy control subjects (n = 145) completed the Perceived Stress Scale (PSS) and documented a range of psychological responses. Groups were balanced for age, sex, education, and living circumstances. RESULTS: Stress was significantly higher in SARS patients than in healthy control subjects. Stress correlated significantly with negative psychological effects. Of SARS patients, 39% (n = 30) were infected health care workers; these individuals reported significantly more fatigue and worries about health than did other patients. Of patients, 25% (n = 20) requested psychological follow-up. CONCLUSIONS: General stress and negative psychological effects are increased in SARS patients, particularly among infected health care workers. This may increase the risk of mood and stress-related disorders. Functional impairment is apparent in the postrecovery phase.

Psychological effects of the SARS outbreak in Hong Kong on high-risk health care workers.

OBJECTIVE: To quantify stress and the psychological impact of severe acute respiratory syndrome (SARS) on high-risk health care workers (HCWs). METHOD: We evaluated 271 HCWs from SARS units and 342 healthy control subjects, using the Perceived Stress Scale (PSS) to assess stress levels and a structured list of putative psychological effects of SARS to assess its psychological effects. Healthy control subjects were balanced for age, sex, education, parenthood, living circumstances, and lack of health care experience. RESULTS: Stress levels were raised in both groups (PSS = 18) but were not relatively increased in the HCWs. HCWs reported significantly more positive (94%, n = 256) and more negative psychological effects (89%, n = 241) from SARS than did control subjects. HCWs declared confidence in infection-control measures. CONCLUSIONS: In HCWs, adaptive responses to stress and the positive effects of infection control training may be protective in future outbreaks. Elevated stress in the population may be an important indicator of future psychiatric morbidity.

Lung pathology of fatal severe acute respiratory syndrome.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a novel infectious disease with global impact. A virus from the family Coronaviridae has been identified as the cause, but the pathogenesis is still unclear. METHODS: Post-mortem tissue samples from six patients who died from SARS in February and March, 2003, and an open lung biopsy from one of these patients were studied by histology and virology. Only one full autopsy was done. Evidence of infection with the SARS-associated coronavirus (SARS-CoV) and human metapneumovirus was sought by reverse-transcriptase PCR and serology. Pathological samples were examined by light and electron microscopy and immunohistochemistry. FINDINGS: All six patients had serological evidence of recent infection with SARS-CoV. Diffuse alveolar damage was common but not universal. Morphological changes identified were bronchial epithelial denudation, loss of cilia, and squamous metaplasia. Secondary bacterial pneumonia was present in one case. A giant-cell infiltrate was seen in four patients, with a pronounced increase in macrophages in the alveoli and the interstitium of the lung. Haemophagocytosis was present in two patients. The alveolar pneumocytes also showed cytomegaly with granular amphophilic cytoplasm. The patient for whom full autopsy was done had atrophy of the white pulp of the spleen. Electron microscopy revealed viral particles in the cytoplasm of epithelial cells corresponding to coronavirus. INTERPRETATION: SARS is associated with epithelial-cell proliferation and an increase in macrophages in the lung. The presence of haemophagocytosis supports the contention that cytokine dysregulation may account, at least partly, for the severity of the clinical disease. The case definition of SARS should acknowledge the range of lung pathology associated with this disease.