Ayy Wu

Severe acute respiratory syndrome: report of treatment and outcome after a major outbreak

Background: The outcome is reported of a prospective uncontrolled study based on a stepwise treatment protocol during an outbreak of severe acute respiratory syndrome (SARS) in Hong Kong. Method: One hundred and thirty eight patients were treated with broad spectrum antibiotics, a combination of ribavirin and low dose corticosteroid, and then intravenous high dose methylprednisolone according to responses. Sustained response to treatment was defined as (1) defervescence for ⩾4 consecutive days, (2) resolution of lung consolidation by >25%, and (3) oxygen independence by the fourth day without fever. Patients with defervescence who achieved either criterion 2 or 3 were classified as partial responders. Patients who fell short of criteria 2 and 3 were non-responders. Results: Laboratory confirmation of SARS coronavirus infection was established in 132 (95.7%). None responded to antibiotics but 25 (18.1%) responded to ribavirin + low dose corticosteroid. Methylprednisolone was used in 107 patients, of whom 95 (88.8%) responded favourably. Evidence of haemolytic anaemia was observed in 49 (36%). A high level of C-reactive protein at presentation was the only independent predictor for use of methylprednisolone (odds ratio 2.18 per 10 mg/dl increase, 95% confidence interval 1.12 to 4.25, p = 0.02). Thirty seven patients (26.8%) required admission to the intensive care unit and 21 (15.2%) required invasive mechanical ventilation. There were 15 deaths (mortality rate 10.9%), most with significant co-morbidities, whereas 122 (88.4%) had been discharged home 4 months after the outbreak onset. Conclusion: The use of high dose pulse methylprednisolone during the clinical course of a SARS outbreak was associated with clinical improvement, but randomised controlled trials are needed to ascertain its efficacy in this condition.

Viral loads in clinical specimens and SARS manifestations.

The number of anatomical sites with detectable viral loads by RT-qPCR appeared to correlate with death risk.

Viral replication in the nasopharynx is associated with diarrhea in patients with severe acute respiratory syndrome

Abstract The role of severe acute respiratory syndrome (SARS) coronavirus as an enteric pathogen was investigated in a cohort of 142 patients with SARS who were treated with a standard treatment protocol. Data from daily hematological, biochemical, radiological, and microbiological investigations were prospectively collected, and the correlation of these findings with diarrhea was retrospectively analyzed. Sixty-nine patients (48.6%) developed diarrhea at a mean (± standard deviation [SD]) of 7.6 ± 2.6 days after the onset of symptoms. The diarrhea was most severe at a mean (±SD) of 8.8 ± 2.4 days after onset, with a maximum frequency of 24 episodes per day (median, 5 episodes; range, 3–24 episodes). A higher mean virus load in nasopharyngeal specimens obtained on day 10 after the onset of symptoms was significantly associated with the occurrence of diarrhea (3.1 log10 vs. 1.8 log10 copies/mL; P = .01) and mortality (6.2 vs. 1.7 log10 copies/mL; P < .01). However, diarrhea was not associated with mortality. The lung and the gastrointestinal tract may react differently to SARS coronavirus infection. Additional investigation of the role of SARS coronavirus in the pathogenesis of diarrhea in patients with SARS should be conducted.

Effect of antibiotics on the bacterial load of meticillin-resistant Staphylococcus aureus colonisation in anterior nares

Prevalence of hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA) infection or colonisation has been associated with antimicrobial consumption. The impact of antibiotic treatment on nasal colonisation is unknown. We conducted a three-month prospective study of 116 patients with extranasal MRSA infection or colonisation, whose nasal MRSA bacterial loads were determined during and after various antibiotic courses over a period of three weeks. Environmental swabs were also taken from the near patient environment. Concomitant nasal MRSA carriage was observed in 76.7% of extranasal MRSA-colonised or -infected patients. The median nasal MRSA bacterial load increased significantly from 2.78 (range 0-6.15) to 5.30 (range 2.90-8.41) log(10) cfu per swab (cfu/swab) (P<0.001) over 21 days during beta-lactam therapy. It also increased from 0 (range 0-4.00) to 4.30 (range 0-7.46) log(10)cfu/swab (P=0.039) over 14 days during fluoroquinolone therapy. Median bacterial loads were significantly higher for beta-lactam- and fluoroquinolone-treated patients on day 7 [4.78, range 0-7.30], day 14 [4.30, range 0-7.60] and day 21 [5.30, range 2.90-8.41] than controls not receiving antibiotics (P<0.05). These loads then decreased by 2-5log(10)cfu/swab 2 weeks after discontinuation of antibiotics. The environment of patients receiving beta-lactam agents (relative risk: 3.55; 95% confidence interval: 1.30-9.62; P=0.018) or fluoroquinolones (4.32; 1.52-12.31; P=0.008) demonstrated more MRSA contamination than the environment around control patients (0.79; 0.67-0.93; P=0.002). Patients on beta-lactam or fluoroquinolone therapy have increased incidence of MRSA colonisation and higher nasal bacterial loads, and appear to spread their MRSA into the near patient environment.

Severe acute respiratory syndrome (SARS): epidemiology and clinical features

Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease with a significant morbidity and mortality. The major clinical features include persistent fever, chills/rigor, myalgia, malaise, dry cough, headache, and dyspnoea. Older subjects may present without the typical febrile response. Common laboratory features include lymphopenia, thrombocytopenia, raised alanine transaminases, lactate dehydrogenase, and creatine kinase. The constellation of compatible clinical and laboratory findings, together with certain characteristic radiological features and lack of clinical response to broad spectrum antibiotics, should arouse suspicion of SARS. Measurement of serum RNA by real time reverse transcriptase-polymerase chain reaction technique has a detection rate of 75%–80% in the first week of the illness.

Lymphocyte surge as a marker for immunorestitution disease due to Pneumocystis jiroveci pneumonia in HIV-negative immunosuppressed hosts

Pneumocystis jiroveci (previously known as Pneumocystis carinii f. sp. hominis) pneumonia (PcP) [1] is a wellknown opportunistic infection affecting immunocompromised hosts, especially patients infected with HIV. However, with the rising number of patients receiving immunosuppressive therapy, PcP is being increasingly recognised in immunosuppressed hosts who are not infected with HIV [2]. For instance, one previous study found PcP in 3.4–43% of solid organ transplant recipients not infected with HIV, with an especially high incidence among patients on long-term steroid therapy [3]. Though the exact pathogenesis of PcP remains obscure, it has been suggested that immunorestitution disease (IRD) contributes to the manifestation of PcP [4]. Reported here are seven cases of PcP manifesting as IRD in HIV-negative immunosuppressed hosts. Between July 1995 and June 2003, 35 patients were diagnosed with PcP at the Queen Mary and United Christian Hospitals in Hong Kong based on the presence of radiologically proven pulmonary infiltrations, the presence of P. jiroveci in bronchoalveolar lavage fluid, and symptoms consistent with the clinical picture of PcP infection, such as fever, cough, and dyspnoea. Twenty-five of the patients were HIV positive; 19 of these patients were newly diagnosed and had not begun highly active antiretroviral therapy (HAART) at the time of presentation. The remaining 10 patients were HIV-negative immunosuppressed subjects with renal diseases (glomerulonephritis in 2, renal transplantation in 1), haematological conditions (immune thrombocytopenic purpura in 2), autoimmune diseases (bullous pemphigoid in 1, pemphigus vulgaris in 1, juvenile rheumatoid arthritis in 1), and solid organ tumour (thymoma in 1). The case of one patient with Cushing’s disease was reported previously [4]. The immunosuppressive therapy administered to these patients consisted of an endogenous steroid in one, steroid therapy in three, and a combination of steroids and cytotoxic treatment in five. Altogether there were 22 male and 13 female patients, and their ages ranged from 7 to 75 years (mean ± SD, 43.3 ±13.9 years). Thirty of them were ethnic Chinese, four were Thai and one was Filipino. The most common clinical presentations of PcP were dyspnoea (80%), fever (80%), non-productive cough (54.3%), and productive cough with clear sputum (31.4%). A minority of the patients presented with chest pain (8.6%), general malaise (8.6%), anorexia (8.6%), dizziness (5.7%), sore throat (5.7%), and diarrhoea (5.7%). Oxygen desaturation with SaO2 <90% while on ambient air occurred in three of the patients. Chest radiographs revealed bilateral lesions in 30 patients, whereas five patients had unilateral involvement. An alveolar pattern of radiographic lesions was shown in 19 patients, whereas interstitial radiographic lesions were found in the remaining 16 patients. Unilateral pleural effusion was noted in one patient upon admission. Pneumothorax was not observed in any of our patients on presentation. None of the 35 patients had received prior chemoprophylaxis for PcP. High-dose intravenous cotrimoxazole was given to 30 patients, and intravenous pentamidine was initiated in the remaining five patients. We defined IRD as an acute symptomatic presentation of PcP temporally related to the recovery of the immune system (as evidenced by an increase in the absolute lymphocyte count), which resulted in immunopathological V. C. C. Cheng . I. F. N. Hung . B. S. F. Tang . K. Y. Yuen (*) Division of Infectious Diseases, Centre of Infection, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China e-mail: kyyuen@hkucc.hku.hk Tel.: +852-28554892 Fax: +852-28551241

Multiple brain abscesses in a patient with bilateral pulmonary arteriovenous malformations and immunoglobulin deficiency

A 34 year old Chinese man presented with grand mal seizures complicating multiple brain abscesses caused by mixed oral flora. Because of persistent hypoxaemia contrast spiral thoracic computed tomography was done, which revealed bilateral pulmonary arteriovenous malformations (PAVMs). Concomitant IgA and IgG subclass deficiency was also found. The combination of these two conditions appears to have predisposed this patient to presumably paradoxical septic embolism. The patient’s cerebral condition responded to postoperative antibiotic treatment and he eventually received selective coil embolisation of right lower lobe PAVMs, which relieved his hypoxaemia and dyspnoea.

Effect of asthma self management programme on asthma morbidity and health care utilization in adult patients admitted to hospital with acute asthma in Hong Kong: A randomised controlled trial

for the 9th Congress of the Asian Pacific Society of Respirology 10–13 December 2004, Hong Kong Editors: Dr K.S. Chan Dr P.C. Wong A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF HOUSE DUST MITE IMMUNOTHERAPY IN ASTHMATIC PATIENTS IN CHINA HONGYU WANG1, XIAOPING LIN2, CHUANGLI HAO3, CHUNQING ZHANG1, BAOQING SUN1, JINGPING ZHENG1, PING CHEN2, JINYUN SHENG3, ADRIAN WU4, NANSHAN ZHONG1 1Guangzhou Institute of Respiratory Diseases, 2Shenyang General Military Hospital, 3Suzhou Children’s Hospital, 4Department of Medicine, The University of Hong Kong Background The purpose of this study was to determine if house dust mite immunotherapy is effective in improving symptom control and reducing rescue medication use in Chinese patients with mild to moderate allergic asthma. Methods This is a double-blind, placebo-controlled study involving 132 asthmatic subjects aged 6 to 45 years recruited from 3 different regions of Mainland China. Subjects were given a 52-week course of Alutard Der P (ALK-Abello, Horsholm, Denmark) treatment or placebo while the dose of inhaled corticosteroids (ICS) was maintained. Results 129 subjects (64 active) completed the study. The symptom scores began to diverge at week 25 with the immunotherapy group showing a significantly lower score until week 48 (P = 0.018). Immunotherapy resulted in a significant decline in symptom (P = 0.003) and medication (P = 0.044) scores during the second half of the treatment period only in subjects who were taking ICS. Subjects on ICS also showed significant improvement in PEF after immunotherapy, but no difference in histamine PC20 was found. Serum ECP and blood eosinophils decreased after immunotherapy in subjects not using ICS. Skin test response decreased in immunotherapy subjects only, and Der P-specific IgE decreased in placebo but not immunotherapy subjects. Immunotherapy resulted in a significantly greater improvement in self-evaluation scores (P < 0.01). Conclusions One year of immunotherapy with Alutard Der P significantly reduced symptoms and medication use in asthmatic subjects, particularly in those who were already using ICS. This was associated with a greater subjective improvement in asthma control. 002 Respirology (2004) 9, (Suppl.) A79–A164 ASSOCIATION OF TOTAL PLASMA IGE LEVELS AND ASTHMA IN ASIAN POPULATIONS WD ZHANG, XZ ZHANG, DW QIU, WC TAN Department of Medicine, National University of Singapore Background Previous studies demonstrated that high levels of serum IgE was associated with asthma and other allergic diseases. Objectives To determine and compare the total plasma IgE levels in both asthmatics and healthy controls in Chinese, Malay and Indian in Singapore. Methods Both 311 asthmatics (Chinese 150; Malay 74; Indian 87) and 355 healthy subjects (Chinese 156; Malay 98; Indian 101) were being participated in a genetic study of asthma. Total plasma IgE levels were determined by Enzyme-linked immunosorbent assay (ELISA). A binary logistic model was used to detect the association between total plasma IgE levels and asthma. Results Plasma total IgE was significantly higher in patients group than that of control group in each ethnicity (Chinese: P = 0.049; Malay: P = 0.002; Indian: P = 0.000). Plasma total IgE (Geometric mean) in Chinese (382 IU/ml) was significantly lower than that in Malay (584 IU/ml) and Indian (990 IU/ml) in the patient group (P = 0.000). However, there was no difference for plasma total IgE among Chinese (256 IU/ml), Malay (226 IU/ml) and Indian (323 IU/ml) (P = 0.385) in the control group. Conclusion High level of plasma total IgE may be a risk factor for asthma in Chinese, Malay and Indian. Total plasma IgE levels showed homogeneous among the three ethnicities. TIME TRENDS IN THE PREVALENCE OF ALLERGIC DISEASES IN GUANGZHOU CHILDHOOD HONGYU WANG, JINGPING ZHENG, NANSHAN ZHONG Guangzhou Institute of Respiratory Disease 510120 Guangzhou, China Objective To examine time trends in the prevalence of asthma, allergic rhinoconjunctivitis and atopic eczema in childhood. Methods 3575 Children aged 13–14 years were randomly selected from ten middle schools in the four central districts of Guangzhou city in 2001. The selection followed the methods used for ISAAC Phase I in 1994–1995. All subjects completed the written questionnaire on asthma, rhinitis and eczema, then finished the video questionnaire about asthma. Results The response rate was 96%, 50.9% of them were female. With the written questionnaire /video questionnaire, the prevalence of wheezing ever, wheezing in the past year, wheezing related to exercise were 8.6%/5.9%, 4.8%/3.8%, 23.4%/11.3% respectively, revealed significantly higher than that were 6.2%/3.2%, 3.4%/2.0%, 17.4%/6.9% in the Phase I (P < 0.001). The prevalence of asthma ever were 4.6%, similar as 3.9% in the Phase I (P > 0.05). The positive response rate to all the questions related to rhinitis and eczema (P < 0.05) except eczema ever (P > 0.05) were significantly higher than that in Phase I. Conclusions The prevalence of asthma, allergic rhinoconjunctivitis and atopic eczema in childhood were increasing during 7 years periods in Guangzhou. STUDY OF ROLE OF INSULIN AND INSULIN RECEPTOR IN ALLERGIC AIRWAY INFLAMMATION OF RATS YL MA, QY HE Department of Pulmonary Medicine People’s Hospital, Peking University, Beijing, P.R.C. 100044 Background Bronchial asthma and type 1 diabetes mellitus (IDDM) are rarely associated in the same subject although the mechanism is still unclear. Methods Streptozotocin and ovalbumin (OVA) were respectively used to induce diabetes mellitus and allergic airway inflammation. 64 male SD rats were divided into 8 groups: group A (asthma); group D (diabetes); group I (insulin treated); group AD (asthma + diabetes); group AI (asthma + insulin treated); group DI (diabetes + insulin treated); group ADI (asthma + diabetes + insulin treated); group C (control). Blood glucose measurements, serum insulin measurements, total and differential leukocyte counts of blood and BALF, HE stained paraffin section of lung tissue were carried out. Immunohistochemistry method was used to describe the distribution of insulin receptor, and the expression of insulin receptor mRNA were measured by RT-PCR. Results After antigen challenge, rats of group A, AI, ADI exhibited airway inflammation characterized by significantly elevated eosinophils and neutrophils, group AD only exhibited mild airway inflammation. Serum insulin levels were higher in groups ADI, AI and A. Immunohistochemistrical staining revealed a diffused distribution pattern of insulin receptor in the lung tissue. Positive cells infiltrating in the lung were increased significantly in groups A, AI and ADI. In groups induced diabetes the expression of insulin receptor mRNA was elevated. Conclusion Administration of low dose insulin aggravated airway inflammation to antigen provocation in rats. Insulin secretion was increased in the presence of inflammation. In the lung of antigen-challenged rats, insulin receptors on the surface of the infiltrating inflammatory cells and bronchial secretory cells were increased. 004 005 003 Saturday 5 April – Respiratory Nurses SIG Oral Presentations (1030–1200) Asthma A80 Respirology (2004) 9, (Suppl.)