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The role of bacteria in exacerbations of COPD. A constructive view.

The role of infection in exacerbations of COPD remains controversial and incompletely understood. Although some investigators believe that bacteria are not important for patients with exacerbation, we disagree and believe that patients with at least two of the three cardinal symptoms of exacerbation should receive antibiotic therapy. With an open-minded view of the area, we review the data, showing that bacteriologic studies, pathologic investigations, and clinical trials all support roles for bacteria and antibiotic therapy in this disease. Still, many questions remain, and future studies will be needed to better define the mechanisms of bacterial invasion in the bronchitic patient and to develop effective vaccines to prevent exacerbations. In the meantime, we must rely on antibiotic therapy, and we will need prospective studies to corroborate preliminary findings showing that different patients may require different therapies; thus, patient subsetting may be vital in the selection of antibiotic therapy for exacerbations of COPD.

Anti-Bacterial Agents↗

Serious asthma exacerbations in asthmatics treated with high-dose formoterol.

OBJECTIVE: To review three prospective, randomized, placebo-controlled, double-blind clinical studies of formoterol (Foradil Aerolizer; Novartis Pharmaceuticals; Basel, Switzerland) at dosages of 12 microg and 24 microg bid for the treatment of patients with asthma. DATA SOURCES: Clinical studies submitted to the US Food and Drug Administration in support of the approval of Foradil Aerolizer for marketing in the United States. RESULTS: More patients treated regularly with formoterol, 24 micro g bid, had a serious asthma exacerbation than did patients who had been treated with placebo. In the first study, 4 of 135 adult patients (3%) who had been treated with formoterol, 24 microg bid, had a serious asthma exacerbation compared to none of 136 placebo-treated patients. In the second study, 5 of 136 patients (3.7%) treated with formoterol, 24 microg bid, had a serious asthma exacerbation compared to 2 of 141 placebo-treated patients (1.4%). In the third study, 11 of 171 pediatric patients (6.4%) treated with formoterol, 24 microg bid, had a serious asthma exacerbation compared to none of 176 placebo-treated patients. CONCLUSION: Regular use of high-dose inhaled formoterol (24 microg bid) may be associated with more frequent serious asthma exacerbations.

Administration, Inhalation↗

Mortality and mortality-related factors after hospitalization for acute exacerbation of COPD.

BACKGROUND: Acute exacerbations form a major component of the socioeconomic burden of COPD. As yet, little information is available about the long-term outcome of patients who have been hospitalized with acute exacerbations, although high mortality rates have been reported. STUDY OBJECTIVE: The aim of this study was to investigate prospectively the outcome for all patients admitted to the hospital with acute exacerbations of COPD during hospital admission and after 1-year of follow-up. Furthermore, patient characteristics related to increased mortality rate were analyzed. DESIGN: We investigated prospectively the 1-year mortality rate and potential determinants of mortality for all patients admitted to the hospital with an acute exacerbation between January 1 and December 31, 1999. RESULTS: A total of 171 patients were included in the study. The mortality rate during hospital stay was 8%, increasing to 23% after 1 year of follow-up. Despite a comparable in-hospital mortality rate (6%), the 1-year mortality rate was significantly higher for patients admitted to the ICU for respiratory failure (35%). The multivariate Cox proportional hazards model was used to determine independent predictors of survival. Variables included in the regression model were age, sex, FEV(1), PaO(2), PaCO(2), body mass index, long-term use of oral corticosteroids, comorbidity index, and hospital readmissions. The maintenance use of oral glucocorticosteroids (relative risk [RR], 5.07; 95% confidence interval [CI], 2.03 to 12.64), PaCO(2) (RR, 1.17; 95% CI, 1.01 to 1.38), and age (RR, 1.07; 95% CI, 1.01 to 1.12) were independently related to mortality. CONCLUSION: We conclude that the prognosis for patients who have been admitted to the hospital for acute exacerbation of COPD is poor. Long-term use of oral corticosteroids, higher PaCO(2), and older age could be identified as risk factors associated with higher mortality.

Adrenal Cortex Hormones↗

The increase in serum soluble ST2 protein upon acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: The human ST2 gene can be specifically induced by growth stimulation in fibroblastic cells, and the soluble ST2 protein (ST2) is expressed preferentially in T-helper type 2 (Th2) cells. Furthermore, ST2 is induced by proinflammatory stimuli such as tumor necrosis factor-alpha and interleukin-1 beta. It has been reported that the inflammatory response in idiopathic pulmonary fibrosis (IPF) is thought to be associated with proinflammatory cytokines and Th2 immune response. STUDY OBJECTIVE: The objective of this study was to evaluate the relevance of the serum ST2 levels in the pathogenesis of IPF. DESIGN: Retrospective study. SETTING: Inpatients in a college hospital. PARTICIPANTS: Forty-nine patients with IPF admitted to our hospital 64 times: 36 patients were admitted once, 11 patients were admitted twice, and 2 patients were admitted three times. The participants also included 200 healthy control volunteers. MEASUREMENTS AND RESULTS: Among 64 events in 49 patients with IPF, 50 of the events occurred in a stable state, and 14 events occurred during acute exacerbation. An acute exacerbation of IPF was defined as an accelerated phase of IPF. The serum ST2 levels were measured by enzyme-linked immunosorbent assay. The serum levels of ST2 in the stable state group did not differ from those in the healthy control group, while the serum levels of ST2 in the acute exacerbation group were significantly higher than those in the stable state group or the healthy control group (p < 0.001, acute exacerbation group vs stable state group or healthy control group; acute exacerbation group, 2.76 +/- 0.56 ng/mL; stable state group, 0.44 +/- 0.07 ng/mL; healthy control group, 0.42 +/- 0.03 ng/mL). Furthermore, serum ST2 statistically correlated with lactate dehydrogenase (r = 0.344, p = 0.005) and C-reactive protein (r = 0.496, p < 0.001), and inversely correlated with PaO(2) (r = - 0.356, p = 0.018) and the percentage of predicted vital capacity (r = - 0.346, p = 0.026). CONCLUSIONS: These results suggest that ST2 protein may increase in the serum, reflecting severity in the inflammatory process and Th2 immune response in the IPF lung.

Acute Disease↗

Prospective multicenter study of relapse following emergency department treatment of COPD exacerbation.

STUDY OBJECTIVES: To determine the incidence and risk factors of relapse after an emergency department (ED) visit for COPD exacerbation. DESIGN: Prospective cohort study as part of the Multicenter Airway Research Collaboration. SETTING: Twenty-nine North American EDs. PATIENTS: ED patients with COPD exacerbations, age > or =55 years. For the present analysis of post-ED relapse, the cohort was restricted to COPD patients who had been discharged from the ED directly to home. MEASUREMENTS AND RESULTS: Eligible patients underwent a structured interview to assess their demographic characteristics, COPD history, and details of the current COPD exacerbation. Data on ED medical management and disposition were obtained by chart review. Patients were contacted by telephone 2 weeks later regarding incident relapse events (ie, urgent clinic or ED visit for worsening COPD). The cohort consisted of 140 COPD patients. Over the next 2 weeks, patients demonstrated a consistent daily relapse rate that summed to 21% (95% confidence interval, 15 to 28%) at day 14. In a multivariate model, the significant risk factors for relapse were the number of urgent clinic or ED visits for COPD exacerbation in the past year (odds ratio [OR], 1.49 [per five visits]), self-reported activity limitation during the past 24 h (OR, 2.93 [per unit on scale of 1 [none] to 4 [severe]), and respiratory rate at ED presentation (OR, 1.76 [per 5 breaths/min]). CONCLUSIONS: Among patients discharged to home after ED treatment of a COPD exacerbation, one in five patients will experience an urgent/emergent relapse event during the next 2 weeks. Both chronic factors (ie, a history of urgent clinic or ED visits) and acute factors (ie, activity limitations and initial respiratory rate) are associated with increased risk. Further research should focus on ways to decrease the relapse rate among these high-risk patients. The clinicians may wish to consider these historical factors when making ED decisions.

Age Distribution↗

Nitrosative stress, heme oxygenase-1 expression and airway inflammation during severe exacerbations of COPD.

STUDY OBJECTIVES: The aim of this study was to examine the relationship between airway inflammation, nitrosative stress, heme-oxygenase expression, and acute severe exacerbations of COPD. DESIGN: We measured heme oxygenase (HO)-1, inducible nitric oxide (NO) synthase expression and nitrotyrosine formation, as well as eosinophilic cationic protein, myeloperoxidase (MPO), interleukin (IL-8), and granulocyte macrophage-colony stimulating factor levels in induced sputum samples from 12 COPD patients (mean +/- SD; FEV1 40 +/- 14% predicted) at the onset of an acute severe exacerbation of COPD requiring hospital admission and 16 weeks after remission. RESULTS: We demonstrated increased percentages (p = 0.001) and absolute numbers (p = 0.028) of total nitrotyrosine positive (+ve) inflammatory cells (ie, polymorphonuclear cells and macrophages), increased percentages (p = 0.04) and absolute numbers (p = 0.05) of total HO-1 +ve inflammatory cells, and increased MPO (p = 0.005) and IL-8 levels (p = 0.028) during severe exacerbation compared with the stable state. CONCLUSIONS: Our results support the hypothesis of an involvement of inflammatory and nitrosative stress in severe COPD exacerbations. Future therapeutic strategies may aim at regulating inflammation and NO synthesis during COPD exacerbations.

Aged↗

Clinical significance of the infection-free interval in the management of acute bacterial exacerbations of chronic bronchitis.

Rational and appropriate antibiotic use for patients with acute exacerbation of chronic bronchitis (AECB) is a major concern, as approximately half of these patients do not have a bacterial infection. Typically, the result of antimicrobial therapy for patients with acute bacterial exacerbation of chronic bronchitis (ABECB) is not eradication of the pathogen but resolution of the acute symptoms. However, the length of time before the next bacterial exacerbation can be another important variable, as the frequency of exacerbations will affect the overall health of the patient and the rate of lung deterioration over time. Clinical trials comparing antimicrobial therapies commonly measure resolution of symptoms in AECB patients as the primary end point, regardless of whether the exacerbation is documented as bacterial in nature. Ideally, the scientific approach to assessing the efficacy of antibiotic therapy for ABECB should include a measurement of acute bacterial eradication rates in patients with documented bronchial bacterial infection followed by measurement of the infection-free interval (IFI), ie, the time to the next ABECB. The use of these variables can provide a standard for comparing various antimicrobial therapies. As we learn more about how antibiotics can affect the IFI, treatment decisions should be adapted to ensure optimal management of ABECB for the long-term.

Acute Disease↗

Histopathologic features and outcome of patients with acute exacerbation of idiopathic pulmonary fibrosis undergoing surgical lung biopsy.

STUDY OBJECTIVES: To define the clinicopathologic features and outcome of acute exacerbation in patients with idiopathic pulmonary fibrosis (IPF) undergoing surgical lung biopsy. DESIGN: Retrospective, single-center study. SETTING: Tertiary care, referral medical center. PATIENTS: Seven patients with acute exacerbation of IPF who underwent surgical lung biopsy. RESULTS: The median age of these seven patients was 70 years (range, 59 to 74 years); two were women. Five patients had a smoking history and included two current smokers. All patients were experiencing an exacerbation of dyspnea for a median duration of 14 days (range, 7 to 28 days) prior to presentation. In three of these patients, the acute deterioration was the presenting feature of IPF, while in the remaining four patients the diagnosis of IPF had previously been established. Chest radiography demonstrated bilateral mixed alveolar-interstitial infiltrates in all of them. CT revealed ground-glass opacities and consolidation bilaterally in all patients with associated peripheral honeycombing in six of them. Echocardiography was performed in six patients and demonstrated pulmonary hypertension in all. BAL fluid was obtained in five patients and revealed neutrophilia in all. Surgical lung biopsy showed diffuse alveolar damage (DAD) in five patients with associated collagen fibrosis and honeycomb changes typical of usual interstitial pneumonia (UIP). One biopsy showed a combination of UIP and organizing pneumonia, while one biopsy showed only DAD. Despite treatment with lung-protective ventilation strategies and high-dose systemic corticosteroids, six patients (86%) died during their hospitalization. CONCLUSIONS: Although IPF is typically associated with an insidious, slowly progressive clinical course, acute exacerbations occur and may be the presenting manifestation in some patients. In either situation, current management strategies including high-dose corticosteroid therapy appear to be relatively ineffective for these patients with acute exacerbation undergoing surgical lung biopsy.

Aged↗

Role of gastroesophageal reflux symptoms in exacerbations of COPD.

BACKGROUND AND AIMS: The impact of gastroesophageal reflux disease (GERD) on exacerbations of COPD has never been evaluated. The aims of this investigation were to determine the prevalence of gastroesophageal reflux (GER) symptoms in COPD patients and the effect of GER on the rate of exacerbations of COPD per year. METHODS: A questionnaire-based, cross sectional survey was performed. Subjects were recruited from the outpatient pulmonary clinics at the University of Florida Health Science Center/Jacksonville. Included patients had an established diagnosis of COPD. Exclusion criteria were respiratory disorders other than COPD, known esophageal disease, active peptic ulcer disease, Zollinger-Ellison syndrome, mastocytosis, scleroderma, and current alcohol abuse. Those meeting criteria and agreeing to participate were asked to complete the Mayo Clinic GERD questionnaire by either personal/telephone interview. Clinically significant reflux was defined as heartburn and/or acid regurgitation weekly. Other outcome measures noted were frequency and type of COPD exacerbations. Statistical analysis was performed using the Fisher exact test for categorical data and the independent t test for interval data. RESULTS: Eighty-six patients were enrolled and interviewed (mean age, 67.5 years). Male patients accounted for 55% of the study group. Overall, 37% of patients reported GER symptoms. The mean FEV(1) percentage of predicted was similar in those with or without GER. The rate of exacerbations of COPD was twice as high in patients with GER symptoms compared to those without GER symptoms (3.2/yr vs 1.6/yr, p = 0.02). CONCLUSIONS: The presence of GER symptoms appears to be associated with increased exacerbations of COPD.

Aged↗

Lipid peroxidation and glutathione peroxidase activity in chronic obstructive pulmonary disease exacerbation: prognostic value of malondialdehyde.

Results of recent studies have indicated that during exacerbation of chronic obstructive pulmonary disease (COPD), antioxidant capacity is lower and the levels of lipid peroxidation products are higher than those in age-matched healthy subjects. The aim of this study was to assess the time course of changes in oxidant stress during the treatment of exacerbation of COPD. For this purpose, we measured erythrocyte glutathione peroxidase (GPx) activity and serum levels of the lipid peroxidation product malondialdehyde (MDA) in 18 male patients with acute exacerbation of COPD. Fifteen healthy non-smokers having no history of lung disease served as control subjects. Mean erythrocyte GPx values of patients were 45.54 +/- 9.04 u/gHb on admission and had increased to 72.77 +/- 9.68 by the tenth day of treatment, but still remained lower than those of healthy subjects (83.13 +/- 10.91) (p=0.007). Serum MDA values in patients were Vol. 12, No. 1, 2001 significantly higher (2.68 +/- 1.28 nmol/ml) than those in control subjects (1.04 +/- 0.36 nmol/ml) (p=0.000) and returned to normal values by the tenth day of treatment (1.08 +/- 0.36 nmol/ml) (p=0.766). Erythrocyte GPx values in patients who were current smokers (39.87 +/- 3.82 u/gHb) were lower than those in ex-smokers (49.15 +/- 9.67 u/gHb) (p=0.021). Moreover, serum MDA values in patients who were current smokers (3.32 +/- 1.18 nmol/ml) were higher than those in ex-smokers (1.66 +/- 0.60 nmol/ml) (p=0.007). The results show that oxidative stress in patients with acute exacerbation of COPD is related to higher MDA levels that return to normal conditions during the course of treatment. In conclusion, the results suggest that MDA levels can serve as a marker of prognosis and of the success of treatment of the exacerbation of COPD.

Biomarkers↗

How does home management of asthma exacerbations by parents of inner-city children differ from NHLBI guideline recommendations? National Heart, Lung, and Blood Institute.

OBJECTIVES: 1) To describe the asthma morbidity, primary care practices, and asthma home management of inner-city children with asthma; 2) to determine the responses of parental caretakers to asthma exacerbations in their child; and 3) to compare these responses to the recommendations of the National Heart, Lung, and Blood Institute (NHLBI) asthma guidelines for home management of acute exacerbations of asthma. DESIGN AND METHODS: A 64-item telephone survey was administered between July 1996 and June 1997 to 220 parental caretakers of 2- to 12-year-old children who had been hospitalized with asthma at an inner-city medical center from January, 1995 to February, 1996. Sociodemographics, primary care practices, asthma morbidity, and asthma home management were assessed. Parents were asked what they would do if their child "began wheezing and breathing faster than usual." RESULTS: Morbidity measures indicated that there were an average of 2.5 +/- 4.5 emergency department visits for asthma in the last 6 months, 1.6 +/- 2.2 hospitalizations for asthma in the last 12 months, and 18.1 +/- 17.9 asthma-related school absences in the previous school year. Most, but not all, of the families had primary care providers and most had phone access to them. Half of the families (51%) reported having been given a written asthma action plan. Only 30% of families with children age 5 years and older had peak flow meters. In contrast, almost all families (97%) had equipment for inhalation of beta-agonists. Only 39% of the 181 children with persistent symptoms were receiving daily antiinflammatory agents as recommended in the guidelines of the NHLBI. In response to the scenario of an acute exacerbation of asthma, no one mentioned that they would refer to a written plan, only 1 caretaker would measure peak flow and 36% would give beta-agonists. Two percent would give oral steroids initially, and 1 additional person would do so if wheezing continued 40 minutes later. Only 4% responded that they would contact their clinician. Reports of actual practice differed from the scenario responses in that more people began beta-agonists and oral steroids in response to an exacerbation in the past 6 months than said they would in response to the scenario. CONCLUSION: In this population of previously hospitalized inner-city children with asthma, the NHLBI guidelines for the home management of asthma exacerbations are not being followed. Interventions are needed to affect both clinician and caretaker practices.

Adolescent↗

Is there an optimal corticosteroid regimen for the management of an acute exacerbation of chronic obstructive pulmonary disease?

Systemic corticosteroids are standard of care for the management of an acute exacerbation of chronic obstructive pulmonary disease (COPD). Several prospective, randomized trials demonstrated modest improvements in patient outcomes when short courses of systemic corticosteroids were used. However, the most appropriate dosage regimen remains controversial, as the corticosteroid regimens used in these trials differed greatly, and no studies have directly compared medium-, high-, and low-dose regimens. In addition, data are lacking on the safety, efficacy, and appropriate dosing of systemic corticosteroids in women and in patients with an acute exacerbation of COPD and concomitant pneumonia or severe respiratory failure. Systemic corticosteroid use is associated with several adverse effects that are dose and/or duration dependent. Evidence suggests that higher dose corticosteroid regimens may place patients at increased short-term and long-term risk, without additional clinical benefit. Tapering of systemic corticosteroid regimens, although a common practice, is unnecessary in most circumstances. The risk for hypothalamic-pituitary-adrenal-axis suppression is negligible when low-dose, short-course corticosteroid regimens are used, and no evidence exists to suggest that abruptly stopping a low-dose steroid regimen will increase the risk of disease relapse. Still, no studies have directly compared tapered and non-tapered regimens in patients with an acute exacerbation of COPD. Consistent with clinical guideline recommendations, safety and efficacy data support the use of low-dose corticosteroid regimens such as prednisone 40 mg orally once/day for 10-14 days in most patients with an acute exacerbation of COPD. Further studies are needed to clarify the optimal systemic corticosteroid regimen for an acute exacerbation of COPD.

Acute Disease↗

Pathology of malignant nephrosclerosis with special reference to the difference between histologic manifestations of pure and exacerbated forms.

Fourteen autopsied cases of malignant nephrosclerosis were classified into 6 of pure form in which syndrome of malignant hypertension developed from the beginning of the disease, and 8 of exacerbated form with appearance of the syndrome in the course of essential hypertension. Pathohistological study of these cases elucidated the differences in histologic manifestations between pure and exacerbated forms of malignant nephrosclerosis as to which little had been known as yet. In the pure form arterioles and small arteries characteristically demonstrated acute or recent lesions such as fibrinoid necrosis and hemorrhage into intima, and intimal cellular hyperplasia of somewhat longer duration, whereas in the exacerbated form coexistence of vascular lesions of various intensities and durations, acute (fibrinoid necrosis and hemorrhage), intermediate (intimal cellular hyperplasia) to chronic (sclerosis and lamellar elastosis), and superposition of more recent vascular lesions on more advanced or older ones were noted. Superposition of vascular alterations was interpreted to be not necessarily specific for exacerbated form but histologic manifestation of recurrence which is liable to be the case more frequently in exacerbated form than in pure form in the longer course of essential hypertension or of malignant hypertension. Some other related problems were also considered and discussed.

Adult↗

High-resolution CT in the acute exacerbation of cystic fibrosis: evaluation of acute findings, reversibility of those findings, and clinical correlation.

OBJECTIVE: The aims of this study were threefold: to compare high-resolution CT (HRCT) of adult patients with cystic fibrosis (CF) during acute exacerbations with asymptomatic patients with CF, to evaluate reversibility of HRCT abnormalities after exacerbations, and to correlate HRCT with clinical parameters. SUBJECTS AND METHODS: Nineteen symptomatic and eight asymptomatic patients were prospectively evaluated by HRCT and pulmonary function tests (PFTs). Symptomatic patients were reassessed 2 weeks after the exacerbation. Studies were independently reviewed by two radiologists using a modified Bhalla scoring system, noting the presence, extent, and severity of bronchiectasis, peribronchial thickening, mucus plugging, and atelectasis or consolidation. Modifications to the Bhalla system included evaluation of the presence and profusion of centrilobular nodules and air-fluid levels within bronchiectatic cavities. The highest possible score was 24 points. Higher scores indicated greater severity. Mosaic perfusion was noted but not included in the modified Bhalla HRCT score. Total modified Bhalla HRCT score and components of the HRCT score were correlated with corresponding PFT parameters. RESULTS: Bronchiectasis, peribronchial thickening, mucus plugging, centrilobular nodules, and mosaic perfusion were identified in symptomatic and asymptomatic patients. Air-fluid levels in bronchiectatic cavities, identified in two patients, represented the only finding limited to acute exacerbation. Reversible findings included air-fluid levels (100%), centrilobular nodules (36%), mucus plugging (33%), and peribronchial thickening (11%). Total HRCT severity scores of symptomatic and asymptomatic patients correlated with forced vital capacity (FVC) (r = .44, p = .01) and forced expiratory volume at 1 sec (FEV1) (r = .34, p = .04). Severity of bronchiectasis correlated with FVC (r = .50, p = .004) and FEV1 (r = .40, p = .02). Mucus plugging and centrilobular nodules did not correlate with PFT parameters. In the symptomatic patients, improvement in HRCT score correlated with changes in FEV1/FVC (r = .39, p = .049). CONCLUSION: Air-fluid levels in bronchiectatic cavities were the only parenchymal finding shown by HRCT that was limited to the acute exacerbation of CF in our study population. However, this finding was rare, being seen in two of 19 patients. Mucus plugging, centrilobular nodules, and peribronchial thickening were potentially reversible findings in symptomatic patients. HRCT accurately revealed disease severity in patients with CF. We also found that changes in HRCT scores correlated with clinical improvement as determined by PFTs.

Acute Disease↗

Importance of adequate immunosuppressive therapy for the recovery of patients with "life-threatening" severe exacerbation of chronic hepatitis B.

AIM: Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes developing into fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in "clinically severe" exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with life-threatening severe exacerbation of chronic hepatitis B. METHODS: Twenty-two patients, 14 men and 8 women, were defined as "severe" exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 d after the diagnosis of severe disease ("early high-dose" group) and 11 patients were either treated more than 10 d or untreated with corticosteroids ("non-early high-dose" group). RESULTS: Mean age, male-to-female ratio, mean prothrombin time (PT) activity, alanine transaminase (ALT) level, total bilirubin level, positivity of HBeAg, mean IgM-HBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the "early high-dose" group survived, while only 2 of 11 patients of the "non-early high-dose" group survived (P<0.001). During the first 2 wk after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the "early high-dose" group. Both ALT levels and HBV DNA polymerase levels fell in both groups. CONCLUSION: The introduction of high-dose corticosteroid can reverse deterioration in patients with "clinically life-threatening" severe exacerbation of chronic hepatitis B, when used in the early stage of illness.

Acute Disease↗

Treatment of hepatocellular carcinoma and the exacerbation of liver function.

We performed interventional treatments on 50 patients with hepatocellular carcinoma (HCC) and analyzed the relationship between these treatments and the exacerbation of liver function after treatment. The different treatments included transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), selective segmental sclerotherapy (SSS), combined TAE and PEIT, or transcatheter arterial chemo-injection (TAI). Thirteen patients showed an exacerbation of liver function after treatment. The laboratory data on admission, showed the lower levels of serum albumin and cholinesterase in this group. In comparison to patients who did not show any exacerbation of liver function, these 13 patients had undergone combined TAE and PEIT. An analysis of cases after TAE and PEIT treatment revealed that the time from TAE to PEIT was shorter in the exacerbation group than in the non-exacerbation group, however, there was no significant difference in the amount of injected ethanol between the two groups. It is assumed that the values of albumin and cholinesterase before treatment, or the period from TAE to PEIT are related to liver failure after treatment. Combining TAE and PEIT treatment may be effective for HCC, however, we should pay special attention to liver failure after treatment.

Administration, Cutaneous↗

Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease.

The effects of broad-spectrum antibiotic and placebo therapy in patients with chronic obstructive pulmonary disease in exacerbation were compared in a randomized, double-blinded, crossover trial. Exacerbations were defined in terms of increased dyspnea, sputum production, and sputum purulence. Exacerbations were followed at 3-day intervals by home visits, and those that resolved in 21 days were designated treatment successes. Treatment failures included exacerbations in which symptoms did not resolve but no intervention was necessary, and those in which the patient's condition deteriorated so that intervention was necessary. Over 3.5 years in 173 patients, 362 exacerbations were treated, 180 with placebo and 182 with antibiotic. The success rate with placebo was 55% and with antibiotic 68%. The rate of failure with deterioration was 19% with placebo and 10% with antibiotic. There was a significant benefit associated with antibiotic. Peak flow recovered more rapidly with antibiotic treatment than with placebo. Side effects were uncommon and did not differ between antibiotic and placebo.

Aged↗

Do life events or depression exacerbate inflammatory bowel disease? A prospective study.

OBJECTIVE: To determine whether depressed mood or life events are associated with an exacerbation of inflammatory bowel disease. DESIGN: A prospective study of a consecutive sample of patients with relapsing inflammatory bowel disease, followed by monthly questionnaires and periodic office visits. SETTING: A referral-based gastroenterology clinic at a medical school. PATIENTS: A consecutive sample of 32 patients with inflammatory bowel disease who had had at least one relapse in a 2-year period after entry into the study. MEASUREMENTS AND MAIN RESULTS: The Social Readjustment Rating Scale (measuring life events), the Beck Depression Inventory (a visual analog scale for depressed mood) and an inventory of intestinal symptoms were completed monthly by each subject with a 78% rate of compliance. A mean of 2.2 exacerbations was seen per subject during the study period. Life events were not temporally associated with changes in intestinal symptoms. Significant associations were found between intestinal symptoms and the two mood scales (P less than 0.05 for each), but no directionality in symptom occurrence could be detected in a time-lagged analysis. The results were similar when the months preceding exacerbations of inflammatory bowel disease were analyzed separately. CONCLUSIONS: Although these findings suggest that mood changed concurrently with exacerbation of inflammatory bowel disease, no evidence indicated that stressful life events or depressed mood precipitated exacerbations in this study group.

Colitis, Ulcerative↗