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PubMed2002

A randomized clinical trial of nebulized magnesium sulfate in addition to albuterol in the treatment of acute mild-to-moderate asthma exacerbations in adults.

STUDY OBJECTIVE: We sought to compare the efficacy and safety of nebulized magnesium sulfate (MgSO(4)) plus albuterol with that of albuterol alone in adult patients with mild-to-moderate acute asthma exacerbations. METHODS: Patients were randomized to receive nebulized MgSO(4) (384 mg in 6 mL of sterile water) or an equal volume of placebo (normal saline solution) in a double-blind fashion after each dose of nebulized albuterol administered (2.5 mg/3 mL) every 20 minutes for the first hour of the study. Spirometry was performed at baseline and every 20 minutes for 2 hours. Monitoring for safety included vital signs, pulse oximetry, and serum magnesium levels. Improvement in percent predicted forced expiratory volume in 1 second was chosen as a primary efficacy end point. RESULTS: Among 74 patients enrolled, 37 were randomized to each of 2 study groups. There were no statistically or clinically significant differences between the 2 study groups in percent predicted forced expiratory volume in 1 second at any point during the trial or overall. There were no significant differences in vital signs, pulse oximetry, or serum magnesium levels at any point during the study. CONCLUSION: The combination of nebulized MgSO(4) and albuterol provides no benefit in addition to that provided by therapy with albuterol in adult patients with mild-to-moderate asthma exacerbations. The efficacy of nebulized MgSO(4) in patients with severe asthma exacerbations remains unknown.

Administration, Inhalation↗
PubMed2003

Are inhaled corticosteroids effective for acute exacerbations of asthma in children?

If started early and at high doses, the acute use of inhaled corticosteroids (ICS) provides modest benefit in patients with mild exacerbations of asthma. In more severe exacerbations, oral corticosteroids are significantly more effective in preventing hospitalizations and improving lung function. We conclude that ICS should not be used routinely to treat acute exacerbations.

Acute Disease↗
PubMed2000

Vasoactive intestinal peptide (VIP) exacerbates endotoxin-induced uveitis (EIU) in mice.

PURPOSE: We have previously shown that inhibition of the proinflammatory cytokine tumor necrosis factor- (TNF)-alpha exacerbates the inflammatory process of EIU. To further examine this paradoxic phenomenon, we investigated here the effect on EIU of VIP, a neuropeptide that inbibits TNF-alpha production. METHODS: VIP was injected concurrently with endotoxin at doses that induce EIU or lethality in mice. Severity of EIU was measured by counting infiltrating cells in eye sections, at 1 or 5 days post endotoxin injection. Survival of mice was monitored periodically, while serum levels of TNF-alpha, interleukin-(IL)-1beta and IL-10 were determined by caputure ELISA. RESULTS: Treatment with VIP exacerbated EIU but provided partial protection from the lethal endotoxin effect. VIP treatment also reduced serum levels of TNF-alpha and IL-1beta, but increased levels of IL-10. CONCLUSION: This study further established the paradoxical observation that EIU is exacerbated by lowering the levels of circulating pro-inflammatory cytokines, in particular TNF-alpha.

Animals↗
PubMed2002

Granulocyte colony-stimulating factor exacerbates the acute lung injury and pulmonary fibrosis induced by intratracheal administration of bleomycin in rats.

We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on lung injury induced by intratracheal administration of bleomycin (BLM, 2 mg/200 micro1) in rats. In experiment 1, G-CSF (10, 30 and 100 microg/kg/day, s.c.) was administered to rats treated with BLM or saline for 7 days starting immediately after BLM administration. In rats receiving G-CSF alone, a large number of neutrophils were noted in the pulmonary capillaries, although there were no lung lesions. In rats receiving BLM alone, diffuse alveolar damage was observed. The administration of G-CSF to BLM-treated rats increased the total lung lesion per unit of pulmonary parenchyma (total lung lesion %) along with increases in the peripheral neutrophil count and the number of neutrophils infiltrating in the pulmonary lesion in a dose-dependent fashion. In experiment 2, 100 microg/kg/day of G-CSF was administered to rats treated with BLM or saline for up to 28 days starting immediately after BLM administration. The administration of 100 microg/kg/day of G-CSF to BLM-treated rats showed no effects at 14 days but it increased the lung lesion % and the score of lung fibrosis along with the increase in the number of neutrophils infiltrating in the pulmonary lesion at 28 days. These findings suggest that G-CSF administration to BLM-treated rats influenced and exacerbated the BLM-induced acute lung injury, and also exacerbated pulmonary fibrosis in a dose-dependent fashion. The exacerbation of lung injury coincided with the marked increase in the peripheral neutrophil count and the number of neutrophils infiltrating in the pulmonary lesion.

Acute Disease↗
PubMed1992

Acute exacerbations of COPD. How to evaluate severity and treat the underlying cause.

Acute exacerbations of chronic obstructive pulmonary disease occur often. Severity should be established by signs and symptoms and by reference to baseline pulmonary function test results when necessary. If the exacerbation is mild to moderate, treatment should include antibiotics, theophylline, beta agonists, and mucolytics. Severe exacerbations should be treated with these agents plus supplemental oxygen, intravenous corticosteroids, and, when appropriate, intubation and mechanical ventilation.

Adrenal Cortex Hormones↗
PubMed1998

Acute exacerbation of autoimmune liver disease associated with hantaviral infection.

Hantavirus is known to cause haemorrhagic fever with renal syndrome (HFRS). Although liver dysfunction has been reported in HFRS, hepatic manifestations of hantaviral infection have not been well described. We describe a case of autoimmune cholangitis in which an exacerbation of hepatitis was associated with hantaviral infection. Seroconversion of both IgG- and IgM-class antibodies to hantavirus was noted coincident with acute exacerbation of hepatitis, which was resolved promptly by treatment with corticosteroid. No extrahepatic manifestations were noted. This case suggests that hantavirus may trigger acute exacerbation of autoimmune liver disease without extrahepatic manifestations and that it may cause community-acquired hepatitis.

Antibodies, Antinuclear↗
PubMed2004

Paradoxical exacerbation of psoriasis in AIDS: proposed explanations including the potential roles of substance P and gram-negative bacteria.

Psoriasis, a TH1-induced disorder, is not more common in human immunodeficiency virus (HIV) infection than in the general population. However, it may appear for the first time or pre-existing psoriasis may worsen and be difficult to treat in HIV disease. The paradoxical exacerbation of psoriasis in AIDS has not been fully explained. Various explanations have been proposed including (a) the reduction of Langerhans' cells (LCs) in HIV disease, (b) the direct epidermal proliferative effect of HIV, (c) the altered cytokine profile in HIV disease, (d) HIV-induced macrophage nitric oxide (NO) production, (e) the increased CD8/CD4 T-cell ratio in HIV infection and (f) the increased colonization of skin by Staphylococcus aureus. However, the observations that (a) LCs cells play an important role in the pathogenesis of psoriasis and a variety of topical and systemic psoriasis treatments cause a reversible decrease in LC function, (b) psoriasis may improve in end-stage HIV infection, (c) overproduction of some TH2 cytokines and underproduction of IL-2 in HIV infection, and (d) the presence of NO favors a TH2 response over a TH1 response make the first four explanations difficult to interpret. Since psoriasis is exacerbated in HIV infection possibly due to the increased staphylococcal colonization, and psoriatic keratinocytes could aggravate HIV infection through production of TNF-alpha, it could be reasoned that in HIV-positive psoriatics a strong vicious cycle is present between the degree of immune deficiency and the staphylococcal colonization, explaining the poor prognosis of both AIDS and psoriasis in these patients. With reference to the studies which indicate significant involvement of substance P (SP) in the pathogenesis of psoriasis and on the other hand increased release of this agent by HIV-infected immune cells it is proposed that SP plays an important role in creating the paradox. Since in HIV-positive psoriatics the source of SP is largely immune cells not neurons, capsaicin, which exerts its action selectively on a subpopulation of neurons, could not be of significant therapeutic value. As SP significantly enhances HIV-1 replication in latently infected immune cells, psoriatic lesions, being heavily infiltrated with immune cells and having high concentrations of SP, could serve as high HIV-replication foci, with the resultant rapid progression of the infection towards AIDS. Additionally, given that lipopolysaccharide is supposed to exacerbate psoriasis, increase of gram-negative infections or cutaneous colonization with these organisms in AIDS may partly explain the paradox. Understanding the HIV-induced immunodysregulation that is associated with psoriasis in some HIV-seropositive patients may assist in the delineation of the immunopathogenesis of the disease in HIV-seronegative psoriatics.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Exacerbations of COPD diagnosed in primary care: changes in spirometry and relationship to symptoms.

The study objective was to assess spirometric changes during resolution of acute exacerbations of COPD diagnosed and treated in primary care and their relationship to clinical features. Spirometry was carried out on 101 patients with AECOPD presenting to a primary care physician on the day of presentation, days 5, 10-14, 28, and 56 after presentation and traces were analyzed including quality and reproducibility. Eighty-three patients produced at least one technically acceptable spirometer trace at presentation and 60 patients produced acceptable traces at all time points. The increase in FEV1 and VC occurred during the first 5 days after presentation, with a median increase in postbronchodilator FEV1 of 55 ml (IQR, -63 to 128, p = 0.003) and VC of 90 ml (IQR -78 to 308 ml, p < 0.001). The improvement in prebronchodilator values related to the bronchodilator reversibility at presentation and was strongest for VC (by day 28: r = 0.522, p < 0.001). Patients presenting with purulent sputum demonstrated improvements in FEV1 and VC but this was limited to FEV1 in those with mucoid sputum. The initial dyspnoea score related to the changes in spirometry. It is possible to obtain clinically useful spirometric traces in most patients presenting with an acute exacerbation in primary care. Some patients present with changes in sputum characteristics and cough without increased breathlessness. However, exacerbations characterized by increased breathlessness are associated with increases in airflow obstruction that may be influenced by sputum characteristics and/or changes in airway reactivity.

Adult↗
PubMed2004

The workplace impact of acute exacerbations of chronic bronchitis (AECB); A literature review.

Acute exacerbations of chronic bronchitis (AECB) are known to have a substantial economic burden in terms of medical care costs. The objective of this study was to assess workplace-based costs associated with AECB, including absenteeism and decreased productivity, based on a review of published literature. A secondary goal was to identify factors related to workplace-based costs in AECB. A literature search was conducted to identify relevant articles assessing one or more aspects of work loss or workplace costs among patients with chronic bronchitis. A review of the identified literature indicates that patients with chronic bronchitis had more days off work; patients whose exacerbations were treated were less likely to have additional exacerbations and had comparatively less work loss. Findings suggest that clinical outcomes and workplace costs are related. While this relationship is clearer in terms of work loss, further exploration is needed to assess decreased productivity and to evaluate this relationship using objective indicators of absenteeism and productivity rather than recall.

Bronchitis, Chronic↗
PubMed2003

Management of the acute exacerbation of asthma.

All patients with asthma are at risk of having asthma exacerbations characterized by worsening symptoms, airflow obstruction, and an increased requirement for rescue bronchodilators. The goals of managing an asthma exacerbation are prompt recognition and rapid reversal of airflow obstruction to avert relapses and future episodes. Short-acting beta-agonists, oxygen, and corticosteroids form the basis of management of acute asthma exacerbation, but a role is emerging for anticholinergics and newer agents such as levalbuterol and formoterol. Initiation or intensification of long-term controller therapy, treatment of comorbid conditions, avoidance of likely triggers, and timely follow-up care prevent setbacks. Acceptance of current treatment guidelines by physicians and adherence to the recommended clinical regimens by patients are essential for effective management of asthma. The physician should strive to establish a constructive relationship with the patient by addressing the patient's concerns, reaching agreement on the goals of therapy, and developing a written action plan for patient self-management.

Acute Disease↗
PubMed1988

Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens.

BALB/c mice can be protected against a normally fatal Leishmania major infection by immunization with a partially purified, soluble subfraction of the parasite (fraction 9). In this study, we demonstrate that a T cell line established against fraction 9, designated line 9, transfers protection equivalent to that obtained by active immunization. In contrast, T cell lines (lines 1 and 9.2) responsive to a nonprotective soluble fraction (fraction 1) not only failed to protect BALB/c mice against L. major, but exacerbated the infection. Most importantly, in addition to differing in their antigen specificity, protective and exacerbative T cells lines could be distinguished on the basis of the lymphokines produced, a characteristic previously used to separate murine Th cells into two subsets, designated Th1 and Th2. We found that the protective cell line, line 9, displayed the Th1 property of secreting IL-2 and IFN-gamma, while the exacerbating lines secreted IL-4 and IL-5, a characteristic of Th2 cells. Our results demonstrate that Th1 and Th2 cells may have dramatically different effects on the outcome of an infection, and suggest that susceptibility and resistance in experimental leishmaniasis may depend upon a balance between the Th subsets induced.

Animals↗
PubMed1998

Randomized, double-blind study of ciprofloxacin and cefuroxime axetil for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group.

In a prospective, multicenter, double-blind study, the interval to clinical relapse in patients with acute bacterial exacerbations of chronic bronchitis from whom a pretherapy pathogen was isolated was compared following treatment with ciprofloxacin or cefuroxime axetil. Clinical and microbiological responses at the end of therapy were secondary efficacy variables. Outpatients randomly received either ciprofloxacin or cefuroxime axetil (500 mg twice a day for 14 days). Three hundred seven patients with acute exacerbations of chronic bronchitis were enrolled, of whom 208 had an exacerbation due to a bacterial pathogen. Clinical resolution at the end of ciprofloxacin and cefuroxime axetil therapy for patients for whom efficacy could be evaluated was 93% and 90%, respectively. Bacteriologic eradication rates were statistically higher for ciprofloxacin recipients (96% [89 of 93]) than for cefuroxime axetil recipients (82% [80 of 97]) (P < .01). The median infection-free interval was 146 days for ciprofloxacin recipients vs. 178 days for cefuroxime axetil recipients (P = .37). In conclusion, ciprofloxacin was associated with an infection-free interval and clinical response that were similar to those associated with cefuroxime axetil, but the bacteriologic eradication rate associated with ciprofloxacin was statistically significantly higher than that associated with cefuroxime axetil.

Acute Disease↗
PubMed2004

Exacerbation of chronic pain following spinal cord injury.

Because of the high prevalence and the refractory nature of pain following spinal cord injury (SCI), it is important to increase the understanding of what factors aggravate different types of pain. This information is related to pain generating mechanisms and may thus be useful in the diagnosis and management of these difficult pain conditions. The aims of the present study were to (1) identify variables (factors) that exacerbate chronic pain associated with SCI and (2) define the relationships among these patterns of pain exacerbation, specific pain characteristics, and psychological features. A sample out of 159 (75.5%) people with SCI and chronic pain, volunteered to participate in a mail survey. Over 50% of the sample indicated that prolonged sitting, infections, fatigue, muscle spasms, cold weather, and sudden movements exacerbated their pain. A principal components analysis detected five sets of factors that were reported to magnify pain: negative mood, prolonged afferent activity (bowel, bladder, somatic), weather, voluntary physical activity, and transient somatic afferent activity. Negative mood and prolonged afferent activity were frequently and significantly associated with both pain characteristics and psychosocial issues. A multiple regression analysis revealed that a combination of decreased activity levels due to pain (t = 3.54; p < 0.001), pain located in the frontal aspects of torso (including genitals) (t = 2.29; p < 0.05), "burning" (t = 2.26; p < 0.05), or "electric" (t = 2.09; p < 0.05) pain, and a limited perception of life control (t = -2.16; p < 0.05) was significantly associated with a high extent of pain aggravation (R2 = 0.39; p < 0.000).

Adult↗
PubMed2006

Ambient air pollution and asthma exacerbations in children: an eight-city analysis.

The authors investigated the relation between ambient concentrations of five of the Environmental Protection Agency's criteria pollutants and asthma exacerbations (daily symptoms and use of rescue inhalers) among 990 children in eight North American cities during the 22-month prerandomization phase (November 1993-September 1995) of the Childhood Asthma Management Program. Short-term effects of carbon monoxide, nitrogen dioxide, particulate matter less than 10 mum in aerodynamic diameter (PM10), sulfur dioxide, and warm-season ozone were examined in both one-pollutant and two-pollutant models, using lags of up to 2 days. Lags in carbon monoxide and nitrogen dioxide were positively associated with both measures of asthma exacerbation, and the 3-day moving sum of sulfur dioxide levels was marginally related to asthma symptoms. PM10 and ozone were unrelated to exacerbations. The strongest effects tended to be seen with 2-day lags, where a 1-parts-per-million change in carbon monoxide and a 20-parts-per-billion change in nitrogen dioxide were associated with symptom odds ratios of 1.08 (95% confidence interval (CI): 1.02, 1.15) and 1.09 (95% CI: 1.03, 1.15), respectively, and with rate ratios for rescue inhaler use of 1.06 (95% CI: 1.01, 1.10) and 1.05 (95% CI: 1.01, 1.09), respectively. The authors believe that the observed carbon monoxide and nitrogen dioxide associations can probably be attributed to mobile-source emissions, though more research is required.

Air Pollutants↗
PubMedDate not supplied

Disease exacerbation caused by sequential dengue infections: myth or reality?

Dengue can be caused by any one of four viruses that are antigenically related but not cross-protective. It has been proposed that the disease may be more severe if an infection with one dengue serotype follows infection with another serotype. Both experimental and epidemiologic data have been cited to substantiate this concept, but the present reviewer does not find the data convincing. The issue is of practical importance because of its relevance to the use of dengue vaccines now under development. It is impossible to prove that clinical manifestations of dengue are not exacerbated by sequential infections. Negative findings can always be countered by arguments that exacerbation occurs only with certain serotypes, only with certain strains of those serotypes, or only when infections occur at critical intervals. Interested persons can examine the relevant data and decide whether the concept of disease exacerbation following sequential dengue infections is myth or reality.

Dengue↗
PubMedDate not supplied

Comparison of trimethoprim-sulfamethoxazole with ampicillin in acute infectious exacerbations of chronic bronchitis: a double-blind crossover study.

Two separate acute bacterial exacerbations of chronic bronchitis or chronic asthmatic bronchitis were treated in 20 patients in a double-blind crossover study. One course of treatment consisted of 320 mg of trimethoprim (TMP) plus, 1,600 mg of sulfamethoxazole (SMZ) daily and the other of 2 g of ampicillin daily; each drug was given for 14 days. Patients were observed initially, twice a week during therapy, and weekly after therapy. Observations that were recorded included graded chest symptoms and physical findings, vital signs, pulmonary function, hematologic parameters, and objective sputum measurements (daily volume, purulence, differential quantitative cytology, quantitative bacterial counts, physical properties, levels of lactate dehydrogenase with its isoenzymes, levels of myeloperoxidase, and presence of deoxyribonucleic acid fibers). Both antibiotic regimens were effective in resolving these acute bacterial exacerbations. Paired t-test analysis revealed few and minor differences between TMP-SMZ and ampicillin during therapy, although three patients did not complete TMP-SMZ therapy because of adverse reactions. However, the period between the two bacterial exacerbations was significantly longer after ampicillin therapy. Innovative in this investigation are the study design and the objective quantitative measurements of inflammatory response and bacterial populations in sputum.

Acute Disease↗
PubMed1988

A randomized double blind controlled trial comparing two amoxycillin regimens in the treatment of acute exacerbations of chronic bronchitis.

A randomized double blind trial comparing two amoxycillin regimens in the treatment of acute exacerbations of chronic bronchitis was performed. Forty-one patients were entered into the study. Twenty patients received amoxycillin sachets 3g twice daily for three days and 21 patients received amoxycillin capsules 500 mg three times daily for seven days. There was no significant difference between the two groups in terms of duration of hospital admission, reduction in sputum volume, clearance of pus from the sputum or the number of treatment failures. No patient developed unwanted effects from the treatment with high dose amoxycillin. Twenty-eight patients were followed for one year and there was no difference in the number of exacerbations experienced by patients treated with short course high dose therapy compared with low dose therapy. It is concluded that short course high dose amoxycillin may be as effective as conventional course amoxycillin in the treatment of acute exacerbations of chronic bronchitis.

Acute Disease↗
PubMed1995

Evaluation of an antibiotic prescribing protocol for treatment of acute exacerbations of chronic obstructive airways disease in a hospital respiratory unit.

A prescribing protocol for infective exacerbations of chronic obstructive airways disease (COAD), specifying the use of oral amoxycillin 500 mg tid (or erythromycin 500 mg qid if allergic) as first line therapy, and oral ciprofloxacin 500 mg bd as second line treatment, was introduced in 1991. Every third sequential admission was screened for the year preceding (1990) and the year after (1991) the protocol was implemented. Only those patients with a discharge diagnosis of infective exacerbation of COAD, but without pneumonia, were included in the analysis. The two groups (1990 and 1991) were matched in terms of age, sex and pre-treatment given by their General Practitioner (GP), but differed with respect to severity score, with 1991 being more severe. The outcome measures showed that duration of hospital stay was comparable as was duration of treatment. Response to first line therapy was 68% and 67% for 1990 and 1991, respectively. Of those who had received antibiotics from their GP, 67% responded to first line therapy, while of those who had not received antibiotics from their GP 75% responded. Duration of therapy was shorter in first line responders (mean and 95% CI: 7.3 (6.3-8.3) days vs 12.7 (10.1-15.3) days). The mean cost per day antibiotic treatment was reduced by 54.6% (95% CI 52.3-56.9%) from 3.77 pounds to 1.71 pounds. In conclusion, the introduction of antibiotic prescribing guidelines for treatment of infective exacerbations of COAD showed no detrimental effect on outcome measures, but was associated with a significant reduction in the cost of antibiotic therapy.

Anti-Bacterial Agents↗