Recommended assessment and management of sleep disordered breathing in patients with atrial fibrillation, hypertension and heart failure: Taiwan Society of Cardiology/Taiwan Society of sleep Medicine/Taiwan Society of pulmonary and Critical Care Medicine joint consensus statement.

Sleep disordered breathing (SDB) is highly prevalent and may be linked to cardiovascular disease in a bidirectional manner. The Taiwan Society of Cardiology, Taiwan Society of Sleep Medicine and Taiwan Society of Pulmonary and Critical Care Medicine established a task force of experts to evaluate the evidence regarding the assessment and management of SDB in patients with atrial fibrillation (AF), hypertension and heart failure with reduced ejection fraction (HFrEF). The GRADE process was used to assess the evidence associated with 15 formulated questions. The task force developed recommendations and determined strength (Strong, Weak) and direction (For, Against) based on the quality of evidence, balance of benefits and harms, patient values and preferences, and resource use. The resulting 11 recommendations are intended to guide clinicians in determining which the specific patient-care strategy should be utilized by clinicians based on the needs of individual patients.

Experiences with pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension at multiple centers in Taiwan.

BACKGROUND: Of the types of pulmonary hypertension, chronic thromboembolic pulmonary hypertension (CTEPH) may be cured through pulmonary endarterectomy (PEA). In this study, we investigated patient experiences with PEA for CTEPH treatment in Taiwan. METHODS: We retrospectively reviewed the records of patients who underwent PEA in two medical centers between January 2005 and December 2019. We measured the following outcomes: in-hospital complications, improvements in cardiac function and exercise capacity, survival using Kaplan-Meier analysis after PEA. RESULTS: Twenty-seven patients (female: 17) with a mean age of 52.6 years underwent PEA. Pre-operatively, most patients were New York Heart Association functional class (NYHA FC) III (n = 19) and IV (n = 7). The mean periods from the onset of symptoms to diagnosis and from diagnosis to operation were 22.6 and 22.3 months, respectively. After PEA, mean intubation time, and length of intensive care unit and hospital stay were 9, 11, and 20 days, respectively. Most patients' NYHA FCs improved to I (n = 15) and II (n = 10). The mean 6-min walk test (6MWT) result improved by 60.5%. The in-hospital mortality, mean follow-up period, and 5- and 10-year overall survival rates were 3.7%, 77.0 months, 96.3%, and 84.3%, respectively. Furthermore, 5- and 10-year disease-specific survival rates were both 96.3%. CONCLUSION: When pre-operative and post-operative statuses were compared, we found a significant improvement in NYHA FC and 6MWT distance. Our study also found a lower in-hospital mortality rate compared to other published studies, except compared to the newer data provided by the University of California, San Diego group.

Comparing Clinical Outcomes of Tiotropium/Olodaterol, Umeclidinium/Vilanterol, and Indacaterol/Glycopyrronium Fixed-Dose Combination Therapy in Patients with Chronic Obstructive Pulmonary Disease in Taiwan: A Multicenter Cohort Study.

Background: Long-acting beta-agonists (LABA) and long-acting muscarinic antagonists (LAMA) combination therapy improved lung function and health-related quality-of-life and reduced exacerbation rates and dyspnea in symptomatic chronic obstructive pulmonary disease (COPD) patients. We compared the real-world effects of three fixed-dose LABA/LAMA combinations for COPD in Taiwan. Methods: This multicenter, retrospective study evaluated 1-year outcomes after LABA/LAMA combination therapy in patients with symptomatic COPD. Exacerbations and symptoms of COPD, lung functions, and therapy escalation were compared among patients using tiotropium/olodaterol, umeclidinium/vilanterol and indacaterol/glycopyrronium. Propensity score matching (PSM) was applied to balance the baseline characteristics. Results: Data of 1,617 patients were collected. After PSM, time to first moderate-to-severe COPD exacerbation was comparable among three groups, while the annualized rates of the exacerbation (episodes/patient/year) in patients receiving tiotropium/olodaterol (0.19) or umeclidinium/vilanterol (0.17) were significantly lower than those receiving indacaterol/glycopyrronium (0.38). COPD-related symptoms were stable over the treatment period, and there was no significant difference in the changes of symptom scores including CAT and mMRC among three groups at the end of the study period. Conclusion: This study presented valuable real-world outcome in terms of exacerbation and treatment response of COPD patients treated with fixed-dose LABA/LAMA regimens in Taiwan. The annualized rates of moderate-to-severe exacerbation in patients receiving tiotropium/olodaterol or umeclidinium/vilanterol were significantly lower than those receiving indacaterol/glycopyrronium, though the time to first moderate-to-severe exacerbation was similar among different fixed-dose LABA/LAMA combinations.

Large-scale assessment of consistency in sleep stage scoring rules among multiple sleep centers using an interpretable machine learning algorithm.

STUDY OBJECTIVES: Polysomnography is the gold standard in identifying sleep stages; however, there are discrepancies in how technicians use the standards. Because organizing meetings to evaluate this discrepancy and/or reach a consensus among multiple sleep centers is time-consuming, we developed an artificial intelligence system to efficiently evaluate the reliability and consistency of sleep scoring and hence the sleep center quality. METHODS: An interpretable machine learning algorithm was used to evaluate the interrater reliability (IRR) of sleep stage annotation among sleep centers. The artificial intelligence system was trained to learn raters from 1 hospital and was applied to patients from the same or other hospitals. The results were compared with the experts' annotation to determine IRR. Intracenter and intercenter assessments were conducted on 679 patients without sleep apnea from 6 sleep centers in Taiwan. Centers with potential quality issues were identified by the estimated IRR. RESULTS: In the intracenter assessment, the median accuracy ranged from 80.3%-83.3%, with the exception of 1 hospital, which had an accuracy of 72.3%. In the intercenter assessment, the median accuracy ranged from 75.7%-83.3% when the 1 hospital was excluded from testing and training. The performance of the proposed method was higher for the N2, awake, and REM sleep stages than for the N1 and N3 stages. The significant IRR discrepancy of the 1 hospital suggested a quality issue. This quality issue was confirmed by the physicians in charge of the 1 hospital. CONCLUSIONS: The proposed artificial intelligence system proved effective in assessing IRR and hence the sleep center quality.

Performance and Clinical Utility of Various Chronic Obstructive Pulmonary Disease Case-Finding Tools.

BACKGROUND AND AIM: Chronic obstructive pulmonary disease (COPD) is frequently underdiagnosed because of the unavailability of spirometers, especially in resource-limited outpatient settings. This study provides real-world evidence to identify optimal approaches for COPD case finding in outpatient settings. METHODS: This retrospective study enrolled individuals who were at risk of COPD (age ≥40 years, ≥10 pack-years, and ≥1 respiratory symptom). Eligible participants were examined using various COPD case-finding tools, namely the COPD Population Screener (COPD-PS) questionnaire, a COPD prediction (PCOPD) model, and a microspirometer, Spirobank Smart; subsequently, the participants underwent confirmatory spirometry. The definition and confirmation of COPD were based on conventional spirometry. Receiver operating characteristic curve (ROC), area under the curve (AUC), and decision curve analyses were conducted, and a clinical impact curve was constructed. RESULTS: In total, 385 participants took part in the study [284 without COPD (73.77%) and 101 with COPD (26.23%)]. The microspirometer exhibited a higher AUC value than did the COPD-PS questionnaire and the PCOPD model. The AUC for microspirometry was 0.908 (95% confidence interval [CI] = 0.87-0.95), that for the PCOPD model was 0.788 (95% CI = 0.74-0.84), and that for the COPD-PS questionnaire was 0.726 (95% CI = 0.67-0.78). Decision and clinical impact curve analyses revealed that a microspirometry-derived FEV1/FVC ratio of <74% had superior clinical utility to the other measurement tools. CONCLUSION: The PCOPD model and COPD-PS questionnaire were useful for identifying symptomatic patients likely to have COPD, but microspirometry was more accurate and had higher clinical utility. This study provides real-world evidence to identify optimal practices for COPD case finding; such practices ensure that physicians have convenient access to up-to-date evidence when they encounter a symptomatic patient likely to have COPD.

Novel App-Based Portable Spirometer for the Early Detection of COPD.

Chronic obstructive pulmonary disease (COPD) is preventable and treatable. However, many patients remain undiagnosed and untreated due to the underutilization or unavailability of spirometers. Accordingly, we used Spirobank Smart, an app-based spirometer, for facilitating the early detection of COPD in outpatient clinics. This prospective study recruited individuals who were at risk of COPD (i.e., with age of ≥40 years, ≥10 pack-years of smoking, and at least one respiratory symptoms) but had no previous COPD diagnosis. Eligible participants were examined with Spirobank Smart and then underwent confirmatory spirometry (performed using a diagnostic spirometer), regardless of their Spirobank Smart test results. COPD was defined and confirmed using the postbronchodilator forced expiratory volume in 1 s/forced vital capacity values of <0.70 as measured by confirmatory spirometry. A total of 767 participants were enrolled and examined using Spirobank Smart; 370 participants (94.3% men, mean age of 60.9 years and mean 42.6 pack-years of smoking) underwent confirmatory spirometry. Confirmatory spirometry identified COPD in 103 participants (27.8%). At the optimal cutoff point of 0.74 that was determined using Spirobank Smart for COPD diagnosis, the area under the receiver operating characteristic was 0.903 (95% confidence interval (CI) = 0.860-0.947). Multivariate logistic regression revealed that participants who have an FEV1/FVC ratio of <74% that was determined using Spirobank Smart (odds ratio (OR) = 58.58, 95% CI = 27.29-125.75) and old age (OR = 3.23, 95% CI = 1.04-10.07 for 60 ≤ age < 65; OR = 5.82, 95% CI = 2.22-15.27 for age ≥ 65) had a higher risk of COPD. The Spirobank Smart is a simple and adequate tool for early COPD detection in outpatient clinics. Early diagnosis and appropriate therapy based on GOLD guidelines can positively influence respiratory symptoms and quality of life.

Fenofibrate Facilitates Post-Active Tuberculosis Infection in Macrophages and is Associated with Higher Mortality in Patients under Long-Term Treatment.

BACKGROUND: Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that infects and persists in macrophages. This study aimed to investigate the effects of long-term fenofibrate treatment in patients with tuberculosis (TB), and the intracellular viability of Mtb in human macrophages. METHODS: Epidemiological data from the National Health Insurance Research Database of Taiwan were used to present outcomes of TB patients treated with fenofibrate. In the laboratory, we assessed Mtb infection in macrophages treated with or without fenofibrate. Mtb growth, lipid accumulation in macrophages, and expression of transcriptional genes were examined. RESULTS: During 11 years of follow-up, TB patients treated with fenofibrate presented a higher risk of mortality. Longer duration of fenofibrate use was associated with a significantly higher risk of mortality. Treatment with fenofibrate significantly increased the number of bacilli in human macrophages in vitro. Fenofibrate did not reduce, but induced an increasing trend in the intracellular lipid content of macrophages. In addition, dormant genes of Mtb, icl1, tgs1, and devR, were markedly upregulated in response to fenofibrate treatment. Our results suggest that fenofibrate may facilitate intracellular Mtb persistence. CONCLUSIONS: Our data shows that long-term treatment with fenofibrate in TB patients is associated with a higher mortality. The underlying mechanisms may partly be explained by the upregulation of Mtb genes involved in lipid metabolism, enhanced intracellular growth of Mtb, and the ability of Mtb to sustain a nutrient-rich reservoir in human macrophages, observed during treatment with fenofibrate.

Building a model to precisely target the responders of a novel intermittent negative air pressure device-with mechanism definition.

OBJECTIVE: Due to the complexity of obstructive sleep apnea syndrome (OSAS), engaging patients in the right treatment poses a constant challenge. A novel oral pressure therapy device, the intermittent negative air pressure Sleep Therapy System (iNAP), has proven to ameliorate respiratory events for OSAS patients. However, the mode of action and the characteristics of its responders are not yet fully understood. Therefore, we have first disclosed the mechanism and provided systemic models to predict the treatment response. METHODS: Series of imaging studies were carried out to differentiate the anatomical features of iNAP responders versus non-responders. Compatible electroencephalography was used to evaluate sleep status during magnetic resonance imaging (MRI) assessments. RESULTS: The upper airway volume was statistically widened under the iNAP treatment while patients were naturally asleep (p < 0.05). Negative predictors included several parameters related to oral-tissue redundancy, enlarged middle pharyngeal space, and longer distance of hyoidale to mandibular plane. Positive predictors included larger angulation of sella-articulate-gonion, longer distance of anterior nasal spine to posterior nasal spine, and elongated tongue, which could correspond to the fact that the iNAP had a greater ability to widen the retropalatal region. Furthermore, algorithms developed by these predictors were built to predict treatment response. CONCLUSIONS: We were able to confirm the effect of the iNAP in widening the upper airway. Anatomic features that can be visually observed or obtained through X-ray films, accompanied with the resulting algorithms, were provided to facilitate physicians' ability to predict patients' treatment response to the iNAP with greater sensitivity and efficiency.

Bronchodilatation effects of a small volume spacer used with a metered-dose inhaler.

BACKGROUND AND OBJECTIVE: In an effort to improve the delivery of drugs to the lungs, various spacer devices have been developed to attach to metered-dose inhalers (MDIs). The aim of the study was to determine whether use of a small volume tube spacer with MDI is associated with better bronchodilatation. METHODS: We assessed bronchodilatation by measuring forced expiratory volume in 1 second (FEV(1)) before and after inhalation of fenoterol 0.4 mg (2 puffs) delivered by using a MDI in four different ways: with or without a spacer alone or with a mouth rinse of 100 mL of water immediately after inhalation with or without a spacer. Results. A total of 303 patients who had a positive bronchodilator test were studied. There was no significant difference in the Delta FEV(1) (mL or %) with or without a spacer (MDI + spacer vs. MDI, mean +/- SD, 365.1 +/- 146.5 mL vs. 356.3 +/- 131.1 mL, p = 0.696; and 21.4 +/- 9.4% vs. 21.4 +/- 9.5%, p = 0.968, respectively). When patients rinsed their mouth after inhalation, bronchodilatation was significantly less in those using an MDI alone compared with MDI + spacer (302.6 +/- 116.5 mL vs. 367.6 +/- 128.3 mL, p = 0.002; and 18.0% +/- 7.9% vs. 21.7% +/- 9.5%, p = 0.013, respectively). CONCLUSIONS: When patients correctly use an MDI, addition of a spacer does not significantly improve bronchodilatation. However, if the mouth is rinsed after inhalation, a spacer does yield better bronchodilatation. Our results suggest that systemic effects from bronchodilator inhalation may not be negligible.

Triggering receptor expressed on myeloid cells-1 in pleural effusions: a marker of inflammatory disease.

BACKGROUND: Triggering receptor expressed on myeloid cells (TREM)-1 is a recently described molecule that plays an important role in myeloid cell-activated inflammatory responses. The aim of this study was to investigate the expression of TREM-1 in pleural effusions of various causes. METHODS: For this cross-sectional, observational study conducted between February and August 2005 in Taiwan, 74 patients with pleural effusions of varying etiology were investigated. Soluble TREM-1 (sTREM-1) was measured in pleural fluid samples, and cells in the fluid were assessed for surface expression of TREM-1. RESULTS: Concentrations of sTREM-1 were significantly higher in infectious and neoplastic pleural effusions (189.1+/-36.7 and 69.9+/-22.8ng/ml, mean+/-sem) than in transudates (10.1+/-5.3ng/ml; P<0.001). Among infectious effusions, the sTREM-1 levels were significantly higher in parapneumonic than in tuberculous effusions (301.8+/-49.8 vs. 38.9+/-17.3ng/ml; P<0.001). TREM-1 was expressed on a portion of the myeloid (CD11b positive) cells in each type of effusion, without significant differences among them (transudative, 34.7%; neoplastic, 36.0%; parapneumonic, 27.7%; tuberculous, 21.2%; P=0.861). Non-myeloid cells expressed very little TREM-1 (transudative, 6.3%; neoplastic, 0.5%; parapneumonic, 1.0%; tuberculous, 0.7%; P=0.192). CONCLUSIONS: sTREM-1 expression in pleural fluids is highest in parapneumonic and neoplastic effusions but low in transudates. In infectious effusions, a high concentration of sTREM-1 may exclude tuberculous pleurisy.

Viral load and outcome in SARS infection: the role of personal protective equipment in the emergency department.

This study was conducted to evaluate the effectiveness of personal protective equipment (PPE) against severe acute respiratory syndrome (SARS). Sixteen patients in a SARS cluster, including 4 health care workers (HCWs) and 12 non-HCWs were studied. We compared the initial viral load by nasopharyngeal swabs, clinical progression, and outcome of this cluster. The HCWs had a lower viral load. The non-HCWs had a higher mean C-reactive protein, lower oxygen saturation, and a higher incidence of intubation and death. Secondary household transmission developed in three of the non-HCWs' families. One month after discharge, non-HCWs had more signs of fibrosis on high resolution computed tomography (HRCT) scan and an impaired pulmonary function test. Although most of the PPE do not confer absolute protection against SARS, it seems that they may lower exposure to the virus, leading to a lower risk of secondary transmission, and be associated with relatively mild disease and a better early outcome.

Adverse effects of ribavirin and outcome in severe acute respiratory syndrome: experience in two medical centers.

STUDY OBJECTIVES: To assess the effect of ribavirin-induced anemia on the outcome of severe acute respiratory syndrome (SARS). DESIGN: A retrospective observational study. SETTING: Two medical centers in Taiwan. PATIENTS: Forty-four patients with SARS who received ribavirin and 7 patients with SARS who did not receive ribavirin. MEASUREMENTS AND RESULTS: The mean peak C-reactive protein and lactate dehydrogenase levels were higher in SARS patients who were receiving ribavirin therapy than in SARS patients who were not receiving ribavirin therapy. The mortality was also higher, but the difference was not statistically significant. On multivariate analysis, hemoglobin level was an independent prognostic correlate of hypoxemia or mortality (odds ratio, 2.0; 95% confidence interval, 1.1 to 3.8; p = 0.03). The hemoglobin began decreasing in two thirds of SARS patients (32 of 44 patients; 73%) who were receiving ribavirin 3 days after therapy with the antiviral drug was started. Patients with a drop in hemoglobin level of > 2 g/dL had a significantly higher mortality rate than the other patients. Hypoxemia developed in one third of SARS patients (17 of 44 patients; 39%) who were receiving ribavirin, all of whom were anemic. Of the 17 hypoxemic patients, 11 (65%) had a drop in hemoglobin of > 2 g/dL, and 4 patients (24%) required a blood transfusion. The mean slope of the hemoglobin decrease was significantly steeper (p = 0.001) in hypoxemic patients with SARS who were receiving ribavirin than in the nonhypoxemic patients with SARS who were receiving ribavirin. Only one of seven SARS patients (14%) who was not receiving ribavirin became anemic, but this individual was not hypoxemic. Eventually, 5 of 17 hypoxemic and anemic SARS patients (29%) who were receiving ribavirin died. The combination of hypoxia with anemia was thus significantly associated with a higher mortality (p < 0.001). CONCLUSIONS: Hypoxia combined with anemia increased the risk for death in SARS patients. Unless ribavirin can be shown to be effective against SARS-coronavirus, the risk of anemia posed by this drug argues against its use in SARS patients.

Comparative study of patients with and without SARS who fulfilled the WHO SARS case definition.

To differentiate severe acute respiratory syndrome (SARS) from non-SARS illness, we retrospectively compared 53 patients with probable SARS and 31 patients with non-SARS who were admitted to Mackay Memorial Hospital from April 27 to June 16, 2003. Fever (> 38 degrees C) was the earliest symptom (50/53 SARS vs. 5/31 non-SARS, p < 0.0001), preceding cough by a mean of 4.5 days. The initial chest X-ray study was normal in 22/53 SARS cases versus 5/31 non-SARS cases. SARS patients with an initially normal chest X-ray study developed infiltrates at a mean of 5 +/- 3.44 days after onset of fever (21/22 SARS vs. 0/5 non-SARS). Rapid radiographic progression of unifocal involvement to multifocal infiltrates was seen in 22 of 24 SARS vs. 0 of 26 non-SARS patients (p < 0.0001). Pleural effusion was not present in any SARS patients but was seen in 6 of 26 non-SARS cases (p < 0.0001). Initial lymphopenia, thrombocytopenia, and elevated lactate dehydrogenase were all more common in SARS than non-SARS (p < 0.0001). They may help differentiate SARS from non-SARS if a reliable and rapid diagnostic test is not available.

Clinical and laboratory features of severe acute respiratory syndrome vis-a-vis onset of fever.

STUDY OBJECTIVES: Severe acute respiratory syndrome (SARS) is a rapidly progressive disease caused by a novel coronavirus (CoV) infection. However, the disease presentation is nonspecific. The aim of this study was to define clearly the presentation, clinical progression, and laboratory data in a group of patients who had SARS. DESIGN: Retrospective observational study. SETTING: A tertiary care medical center with 51 negative-pressure isolation rooms in Taipei, Taiwan. PATIENTS: Fifty-three patients with SARS seen between April 27 and June 16, 2003. RESULTS: Fever (ie, temperature > 38 degrees C) was the most common symptom (98%) and the earliest. When admitted to the isolation unit of the hospital for observation, most patients reported nonspecific symptoms associated with their fever. Only two patients with preexisting illnesses had cough on the same day the fever began. Eventually, 39 patients (74%) developed cough, beginning at a mean (+/- SD) time of 4.5 +/- 1.9 days after fever onset, and 35 patients (66%) had diarrhea beginning at a mean time of 6.0 +/- 3.3 days after fever onset. Thirty-one patients (59%) had abnormal findings on chest radiographs on hospital admission, and all but 1 patient (98%) eventually developed lung infiltrates that were consistent with pneumonia. The majority of patients (63%) first developed unifocal infiltrates at a mean time of 4.5 +/- 2.1 days after fever onset, while in 37% of patients the initial infiltrates were multifocal, appearing at a mean time of 5.8 +/- 1.3 days after fever onset. Common laboratory findings included lymphopenia (on hospital admission, 70%; during hospitalization, 95%), thrombocytopenia (on hospital admission, 28%; during hospitalization, 40%), elevated lactate dehydrogenase (on hospital admission, 58%; during hospitalization, 88%), creatine kinase (on hospital admission, 18%; during hospitalization, 32%), and aspartate aminotransferase or alanine aminotransferase levels (on hospital admission, 27%; during hospitalization, 62%). Throat or nasopharyngeal swab for SARS-CoV by reverse transcriptase polymerase chain reaction (PCR) and real-time PCR was positive in 40 of the 47 patients (85%) in whom the test was performed. CONCLUSIONS: None of the presenting symptoms or laboratory findings are pathognomonic for SARS. Even though cough developed in a majority of patients, it did not occur until later in the disease course, suggesting that a cough preceding or concurrent with the onset of fever is less likely to indicate SARS. While PCR for SARS-CoV appears to be the best early diagnostic test currently available, it is clear that better methods are needed to differentiate between SARS and non-SARS illness on initial presentation.

Proteomic profiles of bronchoalveolar lavage fluid from patients with ventilator-associated pneumonia by gel-assisted digestion and 2-D-LC/MS/MS.

Development of ventilator-associated pneumonia (VAP) imposes a significant financial burden to the health care system, yet the therapeutic decisions rely on the conventional, less sensitive microbiological examination. Characterization of proteins secreted into bronchoalveolar lavage fluid (BALF) provides an opportunity for discovery of diagnostic marker candidates for accurate therapeutic decision-making. We report the first global description of the BALF proteome from patients with VAP. Our approach combining gel-assisted digestion followed by SCX fractionation and nano-LC-MS/MS effectively overcame the interference of high salt concentrations in BALF. Semi-quantitative analysis by a simple, label-free approach based on chromatographic peak area intensity revealed that the protein constituents were dramatically different between the non-VAP controls and the VAP group. To our knowledge, the 206 identified proteins present the most comprehensive global proteome map of BALF. The expression of four selected proteins with unique roles, including gelsolin, serum amyloid P-component, vitamin D-binding protein and pyruvate kinase, were significantly higher in BALF from patients with VAP (p <0.05). We demonstrate that this proteomic approach provides in-depth profiling of the BALF proteome, which comprises proteins functionally associated with the pathogenesis of VAP, including those expressed due to stress-induced injury and host immune response to local inflammation.

Neutralizing antibody response and SARS severity.

Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes. With a linear mixed model, neutralizing antibody titer was shown to peak between week 5 and week 8 after onset and to decline thereafter, with a half-life of 6.4 weeks. Patients with a longer illness showed a lower neutralizing antibody response than patients with a shorter illness duration (p = 0.008). When early responders were compared with most patients, who seroconverted on and after week 3 of illness, the small proportion (17.4%) of early responders (antibody detectable within 2 weeks) had a higher death rate (29.6% vs. 7.8%) (Fisher exact test, p = 0.004), had a shorter survival time of <2 weeks (Fisher exact test, p = 0.013), and were more likely to be > 60 years of age (Fisher exact test, p = 0.01). Our findings have implications for understanding the pathogenesis of SARS and for SARS vaccine research and development.