Gastro-oesophageal reflux disease increases the risk of intensive care unit admittance and mechanical ventilation use among patients with chronic obstructive pulmonary disease: a nationwide population-based cohort study.

INTRODUCTION: Gastro-oesophageal reflux disease (GORD) is common among chronic obstructive pulmonary disease (COPD) patients and may have a deleterious effect on COPD prognosis. However, few studies have investigated whether GORD increases the risk of severe outcomes such as intensive care unit (ICU) admittance or mechanical ventilator use among COPD patients. METHODS: Propensity score matching by age, sex, comorbidities and COPD severity was used to match the 1,210 COPD patients with GORD sourced in this study to 2,420 COPD patients without GORD. The Kaplan-Meier method was used to explore the incidence of ICU admittance and machine ventilation with the log rank test being used to test for differences. Cox regression analysis was used to explore the risk of ICU admittance and mechanical ventilation use for patients with and without GORD. RESULTS: During the 12-month follow-up, GORD patients and non-GORD patients had 5.22 and 3.01 ICU admittances per 1000 person-months, and 4.34 and 2.41 mechanical ventilation uses per 1000 person-month, respectively. The log rank test revealed a difference in the incidence of ICU admittance and machine ventilation between the two cohorts. GORD was found to be an independent predicator of ICU admittance (adjusted hazard ratio (HRadj) 1.75, 95% confidence interval (CI) 1.28-2.38) and mechanical ventilation (HRadj 1.92, 95% CI 1.35-2.72). CONCLUSION: This is the first investigation to detect a significantly higher incidence rate and independently increased risk of admission to an ICU and mechanical ventilation use among COPD patients who subsequently developed GORD during the first year following their GORD diagnosis than COPD patients who did not develop GORD.

Transforming growth factor-ß1 and tumor necrosis factor-α are associated with clinical severity and airflow limitation of COPD in an additive manner.

BACKGROUND: The role of tumor necrosis factor-α (TNF-α) and transforming growth factor-ß1 (TGF-ß1) in chronic obstructive pulmonary disease (COPD) is controversial. The purpose of this study was to assess the relationships among polymorphisms, clinical phenotypes, and the serum levels of TNF-α and TGF-ß1. METHODS: Polymorphisms of promoters of TNF-α (rs 361525 and rs 1800629) and TGF-ß1 (rs 1800469) in 110 COPD patients, 110 nonsmoker health controls without COPD, and 34 smokers were evaluated. Pulmonary functions, chest computed tomography, TGF-ß1, and TNF-α were assessed. RESULTS: The genetic polymorphism of TNF-α (rs 361525) was associated with COPD. More severe COPD patients had higher serum levels of TNF-α and TGF-ß1; moreover, serum levels of TGF-ß1of mild COPD patients were higher than normal controls. All of the studied subjects were divided into four groups by the 95th percentile value of control as cutoff serum value of TGF-ß1 (224.35 ρg/ml) or TNF-α (17.56 ρg/ml) to define the high value of TGF-ß1 or TNF-α, which are higher than those cutoff of values (>224.35 or 17.56 ρg/ml). The FEV1 of the group with high TGF-ß1 + low TNF-α or low TGF-ß1 + high TNF-α or high TNF-α + high TGF-ß1 was lower than the group with low TGF-ß1 + low TNF-α group. Moreover, the lowest value of FEV1 was in the group with high TNF-α + high TGF-ß1. CONCLUSIONS: The genetic polymorphism of the TNF-α is associated with COPD. Both TGF-ß1 and TNF-α modulate clinical severity and airflow limitation in an additive manner.

Influence of family caregiver caring behavior on COPD patients' self-care behavior in Taiwan.

BACKGROUND: COPD becomes a long-term burden on family members who serve as day-to-day caregivers, and causes healthcare systems to incur substantial costs. COPD is both preventable and treatable, and one important aspect of COPD treatment is patients' self-management. This study aimed to investigate relationships between self-management and the caregiver burden, and the influence of family caregivers' caring behavior on COPD patients' self-care behavior. METHODS: In a cross-sectional study conducted between March 2007 and January 2008, 192 pairs of COPD patients (age > 40 years, normal cognitive function) and their primary family caregivers were recruited to answer questionnaires measuring COPD characteristics and COPD knowledge (patients and caregivers); functional status, health beliefs, self-efficacy, and self-care (patients); and caring behavior and caregiver response (family members). All questionnaires were shown to have acceptable validity and reliability, and the data were analyzed using univariate and multivariate techniques. RESULTS: Patients' ages, scores in health belief, self-efficacy and disease-related knowledge were shown to correlate with patients' self-care behavior. Patients' self-care behavior was negatively correlated with family caregivers' caring behavior (ρ = -0.21, P = .003), but positively with caring duration of family caregiver caring behavior (ρ = 0.15, P = .037). Patients with a spouse as caregiver exhibited higher self-care ability than patients not married to their caregivers (P = .038). However, patients' self-care behavior decreased with higher family caregivers' COPD knowledge (P = .041) and caring behavior (P = .01), and patients regularly taking medication exhibited low self-care scores. CONCLUSIONS: Family caregivers' caring behavior had a partial negative effect on COPD patients' self-care behavior.

Five-day course of budesonide inhalation suspension is as effective as oral prednisolone in the treatment of mild to severe acute asthma exacerbations in adults.

BACKGROUND: Limited evidence is available on the use of budesonide inhalation suspension (BIS) for the treatment of mild to severe acute asthma exacerbations (AAE) in adults in an inpatient setting. This study was conducted to evaluate the efficacy of a five-day course of BIS compared with oral prednisolone (OP) in the management of adults with AAE. METHODS: A retrospective study examined the response of 28 patients hospitalized with mild to severe acute asthma exacerbation from January 2003 to December 2003. These patients, who were steroid free ≥ 1 yr, were administered a five-day course of BIS (2 × 2 mg bid) or OP (2 × 15 mg bid). PEF, FEV(1) and asthma symptom scores were recorded daily. RESULTS: The BIS (n = 13) and OP (n = 15) treatment groups were comparable at baseline for demographic characteristics and prebronchodilator (fenoterol) FEV(1) of 52.4% predicted normal value and 54.6% predicted normal value, respectively. Mean change of morning PEF was 152 L/min during BIS treatment and 130 L/min for OP treatment; the mean changes of morning forced expiratory volumes in 1 s (FEV(1)) were 1.0 and 0.7 L, respectively. The mean change in daytime symptom scores were -1.6 and -1.3 in the BIS and the OP groups, respectively. Improvements in PEF, FEV(1) and daytime symptom scores were significantly different between baseline and after treatment in each treatment group (p < 0.05). However, improvements in both BIS and OP groups were similar. CONCLUSION: Budesonide inhalation suspension may be an alternative treatment of acute asthma exacerbation in adults who are at risk for systemic corticosteroids.

Trends in COPD mortality and hospitalizations in countries and regions of Asia-Pacific.

BACKGROUND AND OBJECTIVE: The growing burden of COPD in the Asia-Pacific region supports the need for more intensive research and analysis of the epidemiology of COPD to raise awareness of the disease and its causes, to ensure the development of effective national health policies and to facilitate equitable deployment of finite health-care resources in the prevention and management of COPD. This study estimated and compared COPD mortality and hospital morbidity rates and trends in these rates over time across countries and regions of Asia-Pacific. METHODS: Data consistent with standard definitions of COPD (ICD-9/ICD-10) for the period 1991-2004 were obtained from national health statistics agencies. For countries/regions with complete national mortality and hospitalization data (Australia, Pacific Canada (British Columbia, Hong Kong, South Korea and Taiwan), annual age-standardized mortality and hospitalization rates were calculated for men and women aged >or= 40 years. Negative binomial regression modelling was used to estimate rate ratios for country/region, gender and age differences and general trends over time. RESULTS: Mortality rates per 10,000 population ranged 6.4-9.2 in men, 2.1-3.5 in women and 3.7-5.3 overall in 2003. Corresponding ranges for morbidity were 32.6-334.7, 21.2-129 and 28.1-207.3 per 10 000. Trend analysis of data since 1997 produced annual percentage changes in mortality versus hospitalization of -4.4% versus -0.7% in Australia, -3.6% versus 7.5% in Pacific Canada (British Columbia), -7.15% versus -5.6% in Hong Kong and -2.9% versus -4.2% in Taiwan. CONCLUSIONS: In Asia-Pacific, overall mortality and morbidity rates are high and trends in mortality and morbidity vary between countries/regions. Differences in rates and trends for men and women most likely reflect the different trends in historical and prevalent smoking profiles for COPD in the different countries and regions.

Vacuolar serine protease is a major allergen of Cladosporium cladosporioides.

BACKGROUND: Cladosporium is an important allergenic fungus worldwide. We report here a major allergen of C. cladosporioides. METHODS: Major C. cladosporioides allergens were characterized by immunoblotting, N-terminal amino acid sequencing, protein purification and cDNA cloning. RESULTS: Seventy-four sera (38%) from 197 bronchial asthmatic patients demonstrated IgE binding against C. cladosporioides extracts. Among these 74 sera, 41 (55%) and 38 (51%) showed IgE binding against a 36- and a 20-kDa protein of C. cladosporioides, respectively. Both IgE-reacting components reacted with FUM20, a monoclonal antibody against fungal serine proteases. N-terminal amino acid sequencing results suggest that they are vacuolar serine proteases, and the 20-kDa component is possibly a degraded product of the 36-kDa allergen. A corresponding 5'-truncated 1,425-bp cDNA fragment was isolated. The mature protein after N-terminal processing starts with an N-terminal serine that is the ninth residue encoded by the 5'-truncated cDNA. The protein sequence deduced shares 69-72% sequence identity with Penicillium vacuolar serine proteases and was designated as Cla c 9. The purified 36-kDa Cla c 9 allergen showed proteolytic activity with peptide Z-Ala-Ala-Leu-pNA as substrate. IgE cross-reactivity was detected between the purified Cla c 9 and serine protease allergens from Aspergillusfumigatus and Penicillium chrysogenum. CONCLUSION: We identified a vacuolar serine protease as a major allergen of C. cladosporioides (Cla c 9) and a major pan-allergen of prevalent airborne fungi. IgE cross-reactivity among these highly conserved serine protease pan-fungal allergens was also detectable.

Ventilator-induced lung injury (VILI) promotes ischemia/reperfusion lung injury (I/R) and NF-kappaB antibody attenuates both injuries.

RATIONALE: Whether the ventilator-induced lung injury (VILI) superimposed on ischemia/reperfusion injury (I/R) causes synergistic damage has not been well explored. Whether nuclear factor-kappa B (NF-kappaB) antibody has protective effects for both injuries is also unknown. METHODS: I/R and VILI were produced in an isolated rat lung model. Hemodynamics, lung weight gain (LWG), capillary filtration coefficient (K(fc)), cytokines, and lung pathology were assessed. RESULTS: VILI or I/R produced similar permeability pulmonary edema which was reflected by increasing K(fc) and LWG. Cytokine (IL-1beta) up-regulation occurred in both injuries. Pathologic examination showed edema and inflammatory cell infiltration in VILI or I/R. In addition, the alveoli were overdistended and even ruptured because of marked inhomogeneity of inflation in VILI. Furthermore, combined I/R and VILI produced further increases in K(fc), LWG, IL-1beta, as well as more severe pathologic changes. Conversely, less permeability pulmonary edema, pathologic changes and IL-1 expression were found in groups pretreated with anti-NF-kappaB antibody. CONCLUSION: VILI and I/R cause synergistic damage on the lung. I/R or VILI alone or combined can be attenuated by NF-kappaB antibody. NF-kappaB plays an important role in both forms of lung injury. We propose anti-NF-kappaB antibody pretreatment to be beneficial for VILI, I/R and lung transplantation.

Cost analysis of chronic obstructive pulmonary disease in a tertiary care setting in Taiwan.

BACKGROUND AND OBJECTIVE: The prevalence of COPD in the Western Pacific is increasing. The present study determined the total direct health-care costs for the management of COPD patients with differing degrees of disease severity. The study also aimed to find the key cost drivers in the management of COPD. METHODS: COPD patients were recruited from a tertiary care hospital during April 2002 and March 2003. One-year costs were identified by applying cost data to medical information obtained by review of medical records. Costs included those for medications, oxygen therapy, laboratory and diagnostic tests, clinic visits, emergency room visits and hospital stays. RESULTS: There were 160 patients recruited. Patients were categorized by COPD severity: moderate A COPD (50

Exploring the efficacy of a case management model using DOTS in the adherence of patients with pulmonary tuberculosis.

AIM: To explore the efficacy of hospitals using case management with Directly Observed Treatment - Short course (DOTS) to monitor the adherence of patients with pulmonary tuberculosis in Taiwan. BACKGROUND: Non-adherence to anti-tuberculosis chemotherapy is the major problem in treating patients with tuberculosis. Community-based case management coupled with DOTS has been applied to patients with tuberculosis and has resulted in good results in some countries. Taiwan has a high incidence of tuberculosis, and although it has implemented DOTS, the expected increased efficacy has not yet been realized. DESIGN AND METHODS: The study used a quasi-experimental design. Using age and gender as matching factors, 96 subjects were randomly assigned to one of three groups in 2002-2003. Experimental group I was to receive DOTS case management comprising in-hospital education, direct daily observation in the first two months and one home visit per week. Experimental group II received traditional case management comprising in-hospital education and one home visit per month. The control group did not receive any intervention. RESULTS: The adherence, the rate of completion, the treatment success, sputum conversion and chest X-ray improvement of experimental group I were significantly improved compared with experimental group II and the control group. The completion rate in experimental group I was higher than the general rate for Taiwan during the past six years and the treatment success rate met the standards of the World Health Organization. CONCLUSION: Hospitals using case management with DOTS can improve the adherence of tuberculosis patients and the control of tuberculosis-epidemic situations. Relevance to clinical practice. In a rapidly changing healthcare environment, clinical nurses can make a significant contribution to healthcare delivery for tuberculosis patients. This study has provided further insight into the implementation of hospital-to-community level case management using DOTS by nurses.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism, present strategies and future perspectives of therapies.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which manifests as non-cardiogenic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.

Hypoxia-preconditioned mesenchymal stem cells ameliorate ischemia/reperfusion-induced lung injury.

BACKGROUND: Hypoxia preconditioning has been proven to be an effective method to enhance the therapeutic action of mesenchymal stem cells (MSCs). However, the beneficial effects of hypoxic MSCs in ischemia/reperfusion (I/R) lung injury have yet to be investigated. In this study, we hypothesized that the administration of hypoxic MSCs would have a positive therapeutic impact on I/R lung injury at molecular, cellular, and functional levels. METHODS: I/R lung injury was induced in isolated and perfused rat lungs. Hypoxic MSCs were administered in perfusate at a low (2.5×105 cells) and high (1×106 cells) dose. Rats ventilated with a low tidal volume of 6 ml/kg served as controls. Hemodynamics, lung injury indices, inflammatory responses and activation of apoptotic pathways were determined. RESULTS: I/R induced permeability pulmonary edema with capillary leakage and increased levels of reactive oxygen species (ROS), pro-inflammatory cytokines, adhesion molecules, cytosolic cytochrome C, and activated MAPK, NF-κB, and apoptotic pathways. The administration of a low dose of hypoxic MSCs effectively attenuated I/R pathologic lung injury score by inhibiting inflammatory responses associated with the generation of ROS and anti-apoptosis effect, however this effect was not observed with a high dose of hypoxic MSCs. Mechanistically, a low dose of hypoxic MSCs down-regulated P38 MAPK and NF-κB signaling but upregulated glutathione, prostaglandin E2, IL-10, mitochondrial cytochrome C and Bcl-2. MSCs infused at a low dose migrated into interstitial and alveolar spaces and bronchial trees, while MSCs infused at a high dose aggregated in the microcirculation and induced pulmonary embolism. CONCLUSIONS: Hypoxic MSCs can quickly migrate into extravascular lung tissue and adhere to other inflammatory or structure cells and attenuate I/R lung injury through anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms. However, the dose of MSCs needs to be optimized to prevent pulmonary embolism and thrombosis.

Effects of anti-tumor necrosis factor-alpha and anti-intercellular adhesion molecule-1 antibodies on ischemia/reperfusion lung injury.

Inhibition of neutrophil activation and adherence to endothelium by antibodies to tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecules (ICAM-1), respectively, might attenuate ischemia-reperfusion injury (I/R). I/R was conducted in an isolated rat lung model. Anti-TNF-alpha antibody and/or anti-ICAM-1 antibody were added before ischemia or after reperfusion. Hemodynamic changes, lung weight gain (LWG), capillary filtration coefficients (Kfc), and pathologic changes were assessed to evaluate the severity of I/R. The LWG, Kfc, pathological changes and lung injury score of treatment groups with anti-TNF-alpha antibody treatment, either pre-ischemia or during reperfusion, were less than those observed in control groups. Similar findings were found in group treated with anti-ICAM-1 antibody or combination therapy during reperfusion. In contrast, pre-I/R treatment with anti-ICAM-1 antibody induced severe lung edema and failure to complete the experimental procedure. No additional therapeutic effect was found in combination therapy. We conclude that TNF-alpha and ICAM-1 play important roles in I/R. Anti-TNF-alpha antibody has therapeutic and preventive effects on I/R. However, combined therapy with anti-TNF-alpha antibody and anti-ICAM-1 antibody may have no additive effect and need further investigation.

SN50, a Cell-Permeable Inhibitor of Nuclear Factor-κB, Attenuates Ventilator-Induced Lung Injury in an Isolated and Perfused Rat Lung Model.

High tidal volume (VT) ventilation causes the release of various mediators and results in ventilator-induced lung injury (VILI). SN50, a cell-permeable nuclear factor-κB (NF-κB) inhibitory peptide, attenuates inflammation and acute respiratory distress syndrome. However, the mechanisms associated with the effects of SN50 in VILI have not been fully elucidated. We investigated the cellular and molecular mechanisms for the effects of SN50 treatment in VILI. An isolated and perfused rat lung model was exposed to low (5 mL/kg) or high (15 mL/kg) VT ventilation for 6 h. SN50 was administered in the perfusate at the onset of the high-stretch mechanical ventilation. The hemodynamics, lung histological changes, inflammatory responses, and activation of apoptotic pathways were evaluated. VILI was demonstrated by increased pulmonary vascular permeability and lung weight gain, as well as by increased levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), hydrogen peroxide, and macrophage inflammatory protein-2 in the bronchoalveolar lavage fluid. The lung tissue expression of TNF-α, IL-1ß, mitogen-activated protein kinases (MAPKs), caspase-3, and phosphorylation of serine/threonine-specific protein kinase (p-AKT) was greater in the high VT group than in the low VT group. Upregulation and activation of NF-κB was associated with increased lung injury in VILI. SN50 attenuated the inflammatory responses, including the expression of IL-1ß, TNF-α, MPO, MAPKs, and NF-κB. In addition, the downregulation of apoptosis was evaluated using caspase-3 and p-AKT expression. Furthermore, SN50 mitigated the increases in the lung weights, pulmonary vascular permeability, and lung injury. In conclusion, VILI is associated with inflammatory responses and activation of NF-κB. SN50 inhibits the activation of NF-κB and attenuates VILI.

Effect of salmeterol/fluticasone combination on the dynamic changes of lung mechanics in mechanically ventilated COPD patients: a prospective pilot study.

BACKGROUND: The combined therapy of inhaled corticosteroids and long-acting beta-2 agonists for mechanically ventilated patients with COPD has never been explored. Therefore, the aim of this study was to investigate their dynamic effects on lung mechanics and gas exchange. MATERIALS AND METHODS: Ten mechanically ventilated patients with resolution of the causes of acute exacerbations of COPD were included. Four puffs of salmeterol 25 µg/fluticasone 125 µg combination therapy were administered. Lung mechanics, including maximum resistance of the respiratory system (Rrs), end-inspiratory static compliance, peak inspiratory pressure (PIP), plateau pressure, and mean airway pressure along with gas exchange function were measured and analyzed. RESULTS: Salmeterol/fluticasone produced a significant improvement in Rrs and PIP after 30 minutes. With regard to changes in baseline values, salmeterol/fluticasone inhalation had a greater effect on PIP than Rrs. However, the therapeutic effects seemed to lose significance after 3 hours of inhaled corticosteroid/long-acting beta-2 agonist administration. CONCLUSION: The combination of salmeterol/fluticasone-inhaled therapy in mechanically ventilated patients with COPD had a significant benefit in reducing Rrs and PIP.

Evaluation of risk factors for asthma in Taipei City.

BACKGROUND: Asthma has rarely been studied by evaluating all of its trigger factors in 1 study population. Thus, correlations between the concentration of allergen immunoglobulin (Ig) E antibodies and airway limitation or asthma severity remain unclear. METHODS: Five hundred and seventy-nine asthmatic patients were enrolled, and serum specific IgE antibodies to allergens were analyzed. All suspected trigger factors were assessed by questionnaire, case histories over a 4-year period, and diary card recordings; possible trigger factors were then re-evaluated. RESULTS: Antibodies to the following allergens were found: Dermatophagoides pteronyssinus (59.8% of patients), D. microceras (58.8%), D. farinae (56.8%), cockroach (38.3%), dog dander (26.3%), Candida albicans (13.3%), cat dander (10%), and Cladosporium herbarum (6.6%). A greater prevalence of allergy to dog and cat dander was found than previously. Younger patients were more often positive for mite allergens, and had higher titers of antibodies against such allergens, than older patients. Further, females had a lower concentration of mite allergen antibodies than males. No correlation between the concentration of allergen antibodies and forced expiratory volume in 1 second (FEV1), or the ratio of FEV1:forced vital capacity (FEV1:FVC), was found. In addition, there was no significant change in antibody titers with varying asthma severity. Non-allergenic trigger factors were irritant air inhalants (94.6% of patients), respiratory infection (92.2%), exercise (75.2%), emotional factors (58.8%), drugs and chemical substances (16%). CONCLUSION: There are multiple trigger factors in asthma. Allergenic trigger factors are more common in younger than older patients, whereas non-allergenic trigger factors are more common in older patients. There was no linear correlation between the concentration of specific IgE antibodies and asthma severity or airway limitation; therefore, to prevent asthma attacks in individual asthmatic patients, greater attention should be paid to avoiding all potential trigger factors, and not just house dust mite allergens.

Ceftaroline fosamil versus ceftriaxone for the treatment of Asian patients with community-acquired pneumonia: a randomised, controlled, double-blind, phase 3, non-inferiority with nested superiority trial.

BACKGROUND: Ceftriaxone with or without a macrolide antibiotic is a recommended treatment for patients with community-acquired pneumonia requiring hospital admission and intravenous antibiotic treatment. We aimed to assess the efficacy and safety of ceftaroline fosamil compared with ceftriaxone in the treatment of Asian patients admitted to hospital with community-acquired pneumonia. METHODS: In this international, randomised, controlled, double-blind, phase 3, non-inferiority with nested superiority trial, adult Asian patients with Pneumonia Outcomes Research Team (PORT) risk class III-IV acute community-acquired pneumonia were randomly assigned (1:1) to receive intravenous ceftaroline fosamil (600 mg every 12 h) or ceftriaxone (2 g every 24 h) for 5-7 days. Patients were randomly assigned via centralised telephone and web-based system; patients and treating clinicians were masked to treatment allocation. Investigators who did study assessments remained masked to treatment allocation until completion of the study. The primary endpoint was clinical cure at the test-of-cure visit (8-15 days after last dose of study drug) in the clinically evaluable population. Non-inferiority of ceftaroline fosamil was defined as a lower limit of the two-sided 95% CI for the difference in the proportion of patients clinically cured of -10% or higher; if non-inferiority was achieved, superiority was to be concluded if the lower limit of the 95% CI was greater than 0%. This trial is registered with ClinicalTrials.gov, number NCT01371838. FINDINGS: Between Dec 13, 2011, and April 26, 2013, 847 patients were enrolled at 64 centres in China, India, South Korea, Taiwan, and Vietnam, of whom 771 were randomly assigned and 764 received study treatment. In the clinically evaluable population (n=498) 217 (84%) of 258 patients in the ceftaroline fosamil group and 178 (74%) of 240 patients in the ceftriaxone group were clinically cured at the test-of-cure visit (difference 9·9%, 95% CI 2·8-17·1). The superiority of ceftaroline fosamil was consistent across all preplanned patient subgroup analyses (split by age 65 years, age 75 years, sex, PORT risk class, and previous antibiotic use) apart from patients younger than 65 years. The frequency of adverse events was similar between treatment groups and the safety results for ceftaroline fosamil were consistent with the cephalosporin class and previous clinical trial data. INTERPRETATION: Ceftaroline fosamil 600 mg given every 12 h was superior to ceftriaxone 2 g given every 24 h for the treatment of Asian patients with PORT III-IV community-acquired pneumonia. These data suggest that ceftaroline fosamil should be regarded as an alternative to ceftriaxone in empirical treatment regimens for this patient population. FUNDING: AstraZeneca.

Eight-month prospective study of 14 patients with hospital-acquired severe acute respiratory syndrome.

OBJECTIVE: To define the clinical characteristics and clinical course of hospital-acquired severe acute respiratory syndrome (SARS). PATIENTS AND METHODS: This 8-month prospective study of 14 patients with hospital-acquired SARS in Taipei, Taiwan, was conducted from April through December 2003. RESULTS: The most common presenting symptoms in our 14 patients with hospital-acquired SARS were fever, dyspnea, dizziness, malaise, diarrhea, dry cough, muscle pain, and chills. Lymphopenia and elevated serum levels of lactate dehydrogenase (LDH) and C-reactive protein (CRP) were the most common Initial laboratory findings. Initial chest radiographs revealed various pattern abnormalities and normal results. Five of the 14 patients required mechanical ventilation. The need for mechanical ventilation was associated with bilateral lung involvement on the initial chest radiograph and higher peak levels of LDH and CRP. Clinical severity of disease varied from mild to severe. At 8 months after disease onset, patients with mild or moderate SARS had normal findings or only focal fibrosis on chest high-resolution computed tomography. However, bilateral fibrotic changes remained in the 4 patients who had recovered from severe SARS, 1 of whom had mild restrictive ventilatory impairment. One patient with severe SARS died; she was elderly and had other comorbidities. Five additional patients had reduced diffusing capacity. CONCLUSION: The clinical picture of our patients presenting with hospital-acquired SARS revealed atypical pneumonia associated with lymphopenia, elevated serum levels of LDH, rapid clinical deterioration, and lack of response to empirical antibiotic therapy. Substantially elevated levels of LDH and CRP correlated with severe illness requiring mechanical ventilatory support. In those receiving mechanical ventilation, pulmonary function was only mildly reduced at 6 to 8 months after acute illness, consistent with the natural history of acute respiratory distress syndrome due to other causes.

Effect of medical education on quality of life in adult asthma patients.

BACKGROUND AND PURPOSE: Previous studies revealed that many asthma patients did not understand how to manage their disease, which in turn affected their quality of life. This study investigated the effect of asthma education on quality of life in Taiwanese adults with asthma. METHODS: A before and after quasi-experimental design was used. A total of 85 asthma patients were recruited from the asthma clinic of a medical center in northern Taiwan using purposive sampling. Among these patients, 31 were assigned to the experimental group and 54 to the control group. The experimental group received four 1-hour sessions of group education, while the control group received no instruction. Data were collected at 2 different stages: enrollment (baseline), and at 1 month after enrollment. All subjects completed the Asthma Quality of Life Questionnaire and the Asthma General Knowledge Questionnaire for Adults. Data were analyzed using independent-samples t test and paired t test. RESULTS: After completing the asthma education sessions, the mean scores on asthma knowledge significantly increased from 19.65 to 23.06 (p < 0.001) in the experimental group. The mean scores for overall quality of life significantly increased from 5.06 to 5.42 (p < 0.01). The mean scores in the symptom domain and the exposure to environmental stimuli domain also significantly increased from 5.07 to 5.46 (p < 0.01) and 4.94 to 5.52 (p < 0.001) after education. However, the mean scores of the control group on the same questionnaire did not change significantly. CONCLUSION: Asthma education can significantly improve asthma knowledge and quality of life in adult asthma patients.

Management of hospital-acquired severe acute respiratory syndrome with different disease spectrum.

BACKGROUND: Outbreak of severe acute respiratory syndrome (SARS) in Taipei has been associated with Taiwanese back from Guangdong, China. We report 4 probable SARS cases with different severity and propose optimal treatment. METHODS: Four probable SARS cases were enrolled. Two cases were due to outbreak of SARS in our hospital and two cases were transferred from other hospitals. All patients received standard treatment: ribavirin 1000 mg orally daily for 10 days, Levofloxacin 500 mg orally daily for 7 days, and intravenous immunoglobulin (IVIG) 1 g/kg/day for 2 day after the onset of symptoms. If severe hypoxia (PaO2/FiO2 < 200) occurred, protective strategy of mechanical ventilation and methylprednisolone 2 mg/kg/day were given. The clinical pictures and treatment outcome were discussed. RESULTS: Fever, dyspnea, diarrhea, malaise, dizziness and dry cough were initially more common symptoms. Initially chest patterns included focal consolidation, interstitial infiltration or normal. Common laboratory findings were lymphopenia, and elevated serum levels of lactate dehydrogenase and C-reactive protein. No mortality was found. CONCLUSIONS: Highly alert and stringent infection control of SARS cases are required. Otherwise, SARS easily induces hospital-acquired first then community-acquired infection. Initial presentation of radiographic patterns includes normal, interstitial or airspace shadowing. Fever and lymphopenia are occasionally followed by rapidly progressive respiratory compromise. The standard treatment might be beneficial for decreasing the mortality rate.

Inhibitor of nuclear factor-κB, SN50, attenuates lipopolysaccharide-induced lung injury in an isolated and perfused rat lung model.

NF-κB cell permeable inhibitory peptide (SN50) inhibits translocation of nuclear factor-κB (NF-κB) and production of inflammatory cytokines that are implicated in lipopolysaccharide (LPS)-induced lung injury (LPSLI). However, the protective effect of SN50 in LPSLI is unclear. We explored the cellular and molecular mechanisms of SN50 treatment in LPSLI. LPSLI was induced by intratracheal instillation of 10 mg/kg LPS using an isolated and perfused rat lung model. SN50 was administered in the perfusate 15 minutes before LPS was administered. Hemodynamics, lung histologic change, inflammatory responses, and activation of apoptotic pathways were evaluated. After LPSLI, increased pulmonary vascular permeability and lung weight gain was observed. The levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, myeloperoxidase, and macrophage inflammatory protein-2 increased in bronchoalveolar lavage fluids. Lung-tissue expression of TNF-α, IL-1ß, mitogen-activated protein kinases (MAPKs), caspase-3, p-AKT (serine-threonine kinase, also known as protein kinase B), and plasminogen activator inhibitor-1 (PAI-1) was greater in the LPS group compared with controls. Upregulation and activation of NF-κB was associated with increased lung injury in LPSLI. SN50 attenuated the inflammatory responses, including expression of IL-1ß, TNF-α, myeloperoxidase, MAPKs, PAI-1, and NF-κB; downregulation of apoptosis indicated by caspase-3 and p-AKT expression was also observed. In addition, SN50 mitigated the increase in the lung weight, pulmonary vascular permeability, and lung injury. In conclusion, LPSLI is associated with inflammatory responses, apoptosis, and coagulation. NF-κB is an important therapeutic target in the treatment of LPSLI. SN50 inhibits translocation of NF-κB and attenuates LPSLI.