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PubMed1997

Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group.

BACKGROUND: The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide. METHODS: After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days. RESULTS: The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater. CONCLUSIONS: In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma.

Administration, Inhalation↗
PubMed2001

IL-18 might reflect disease activity in mild and moderate asthma exacerbation.

BACKGROUND: IL-18, identified as an IFN-gamma-inducing factor, is a proinflammatory cytokine that plays an important role in TH1 cell activation. Recently, it was reported that histamine induced IL-18 and that IL-18 might act as a coinducer of TH1 and TH2 cytokines. OBJECTIVE: The aim was to evaluate the contribution of IL-18 to asthma exacerbation. METHODS: Serum IL-18, soluble IL-2 receptor, eosinophil cationic protein, and plasma IFN-gamma levels, as well as peak expiratory flow were measured in patients with stable asthma (n = 28), acute mild or moderate asthma (n = 23), or pulmonary sarcoidosis (n = 35) and in healthy subjects (n = 26). We compared the serum IL-18 levels between patients with acute asthma and those in remission and examined the time course in acute exacerbation after asthma therapy. RESULTS: Significantly higher serum IL-18 levels were found in patients with acute asthma (215 +/- 33 pg/mL, mean +/- SE; P = .02) and pulmonary sarcoidosis (239 +/- 27 pg/mL, P = .008) than in control subjects (127 +/- 11 pg/mL), but the plasma IFN-gamma level was significantly elevated in only pulmonary sarcoidosis (P < .001). In pulmonary sarcoidosis the IL-18 values significantly correlated with the IFN-gamma levels (r = 0.61, P < .001), but in acute asthma they did not. The IL-18 levels during acute asthma exacerbation were significantly higher (P = .01) than on remission days. In acute asthma, circulating IL-18 levels significantly correlated with serum soluble IL-2 receptor levels (r = 0.77, P < .0001) but not with serum eosinophil cationic protein levels. The IL-18 level had a tendency to inversely correlate with peak expiratory flow. The elevated IL-18 levels in acute asthma quickly decreased on day 3 (P = .02) and day 7 (P = .002) after therapy. CONCLUSION: It was suggested that IL-18 may play a potential role to activate immunologic responses and may reflect disease activity in mild and moderate asthma exacerbation.

Acute Disease↗
PubMed2000

A single dose of intramuscularly administered dexamethasone acetate is as effective as oral prednisone to treat asthma exacerbations in young children.

OBJECTIVE: To evaluate whether a single dose of intramuscularly administered dexamethasone acetate (IM Dex) was as safe and effective as a 5-day course of oral prednisone (PO Pred) in the treatment of young children with mild-moderate exacerbations of asthma. STUDY DESIGN: A prospective, randomized, investigator-blinded study was done in a tertiary care medical center in children (6 months to 7 years of age) who required corticosteroids to treat mild-moderate asthma exacerbations as outpatients. Patients were randomized to receive either a single dose of IM Dex ( approximately 1.7 mg/kg) or PO Pred ( approximately 2 mg/kg/d for 5 days). Clinical asthma score, behavioral changes, albuterol use, and tolerance of the medication were recorded in a home diary for 7 days. Cortisol/creatinine ratios on first morning void urine samples were obtained on day 14. The primary outcome measures were changes in clinical asthma score through day 5 and tolerance of the medication. RESULTS: Fifteen patients in the IM Dex group (mean age 37 months) and 17 in the PO Pred group (mean age 36 months) completed the study. Clinical asthma score improved significantly in both groups during the first 5 days of therapy, and no significant difference was seen in the rate of improvement between the 2 groups. Three children refused more than 75% of their prednisone doses, and another 4 missed 30% to 50% of the doses despite their parents' best efforts. The intramuscular injection caused no complications, and approximately 70% of parents in both groups stated that they would choose IM Dex to treat their child's next asthma exacerbation. CONCLUSION: In this group of children a single intramuscular injection of dexamethasone acetate was as effective as a 5-day course of PO Pred for the management of mild-moderate outpatient asthma exacerbations.

Administration, Oral↗
PubMedDate not supplied

Systemic corticosteroid therapy for acute asthma exacerbations.

Acute exacerbations of asthma may represent reactions to airway irritants or failures of chronic treatment. The costs to both the patient and society are high. Exacerbations often are frightening episodes that can cause significant morbidity and sometimes death. The emergency department (ED) visits and hospitalizations often required lead to significant health care expenses. Thus, preventing and optimizing management of acute exacerbations is critical. Corticosteroids are a cornerstone of asthma therapy. They have been shown to lower admission rates and reduce risk of relapse. This article provides an overview of the role of corticosteroids (including betamethasone, dexamethasone, methylprednisolone, and prednisolone) in the management of acute asthma exacerbations, with an aim toward effective decision making about the choice of therapy.

Administration, Oral↗
PubMed2003

Susceptibility of lupus-prone NZM mouse strains to lead exacerbation of systemic lupus erythematosus symptoms.

It has been repeatedly shown that the heavy metal mercury can induce or exacerbate lupus like autoimmunity in susceptible strains of rats and mice. A hallmark of such autoimmune induction is the accompaniment of an immune shift, in which there is usually an initial skewing toward a Th2-like immune environment. Another heavy metal, lead (Pb), has also been found to induce a Th2 shift in mice. However, exposure of normal mouse strains to Pb does not appear to induce autoimmunity. In order to investigate whether mice genetically predisposed to murine systemic lupus erythematosus (SLE) are susceptible to a Pb-induced exacerbation of lupus, males and females of four New Zealand mixed (NZM) mouse strains, along with BALB/c and C57Bl/6 controls, were administered three 100-microliter intraperitoneal injections of either 1.31 mM lead or sodium acetate per week for 3 wk. The four NZM strains chosen, NZM391, NZM2328, NZM88, and NZM2758, have differential genetic penetrance for SLE with variances in certain manifestations of the disease, but all of these strains naturally develop glomerulonephritis and produce high titers of anti-nuclear autoantibodies. The mice were prebled for baseline values and were bled directly after the injection period (d 1) and monthly thereafter for 5 mo. Sera were assessed for anti-double-stranded DNA titers, urea nitrogen levels, and creatine kinase activity, as well as four total immunoglobulin (Ig) G2a and IgG1 levels. Mortality and morbidity of the mice were also recorded. All NZM strains showed an acute, non-gender-based, susceptibility to Pb at d 1, but the control strains were unaffected. Over time, it became apparent that the strains diverged: The NZM391 strain showed gender-independent susceptibility to Pb enhancement of lupus manifestations and mortality; the NZM2328 strain exhibited gender-independent Pb susceptibility to manifestations, although only females had increased mortality; the NZM2758 strain exhibited non-gender-based elevations in urea nitrogen and creatine kinase activity levels; and the NZM88 strain displayed male susceptibility to anti-DNA and life span. Surprisingly, Pb increased the longevity of NZM88 and NZM2758 females. These results indicate that Pb indeed can exacerbate SLE in lupus-prone mice; however, even among lupus-prone strains, genetic differences determine the degree of exacerbation. Using the known phenotype and genetic differences, one can identify and characterize possible traits and loci associated with Pb susceptibility.

Analysis of Variance↗
PubMed2004

Exhaled nitric oxide predicts asthma exacerbation.

The fraction of exhaled nitric oxide (FeNO) is elevated in asthmatics compared to normal subjects. Many studies have demonstrated that FeNO correlates with other markers of airway inflammation. The purpose of this study was to assess the clinical utility of routine monitoring of FeNO in determining its ability to predict future asthma exacerbations compared with other standard clinical measures of spirometry, peak flows, quality of life score, medication usage, and symptoms. A convenience sample of 22 patients with moderate and severe-persistent asthma in the University of New Mexico Adult Asthma Clinic were evaluated during a routine clinic visit and then noted whether they had an exacerbation within 2 weeks of the initial appointment. Those with an exacerbation had a higher mean FeNO (29.67 ppb +/- 14.48) compared to those who did not (12.92 ppb +/- 5.17), p = 0.002. A nominal logistic regression model to determine those variables that predict asthma exacerbation found that FeNO was the only significant predictor, p = 0.03. Thus, FeNO appears to be a clinically useful tool to assess disease control in this population.

Adult↗
PubMed2000

Exacerbation of herpes simplex encephalitis after successful treatment with acyclovir.

Herpes simplex encephalitis (HSE) in children sometimes exacerbates after successful treatment; yet the frequency, etiology, and clinical features of exacerbation remain unclear. We report data for 27 children with HSE confirmed by polymerase chain reaction (PCR) analysis; all were successfully treated with acyclovir, but 7 (26%) had a relapse of encephalitic illness. In 2 of those 7, serial examination with a PCR assay showed that herpes simplex virus (HSV) DNA reappeared temporarily in the cerebrospinal fluid (CSF). For 5 of the 7 patients, a second course of acyclovir therapy was effective. Coxsackievirus A9 was isolated from CSF of 1 case patient during subsequent exacerbation. The total dose during initial acyclovir therapy was significantly lower in the relapse group than in the control group (P=.027). In conclusion, exacerbation of HSE in children may be more common than previously recognized. It is suggested that the replication of HSV or another viral pathogen caused a second encephalitic illness (HSE) in some cases.

Acyclovir↗
PubMed1999

RANTES, macrophage-inhibitory protein 1alpha, and the eosinophil product major basic protein are released into upper respiratory secretions during virus-induced asthma exacerbations in children.

The presence of cytokines and the toxic eosinophil granule product major basic protein (MBP) was investigated in nasal aspirates from children with naturally occurring virus-induced asthma exacerbations and compared with levels in nasal aspirates taken from the same children when asymptomatic. Increased levels of MBP accompanied by increased levels of the chemokines RANTES and macrophage-inhibitory protein 1alpha were observed in nasal aspirates from children during the virus-induced exacerbations. Granulocyte-macrophage colony-stimulating factor was mostly undetectable in samples obtained during both symptomatic and asymptomatic periods. Interleukin-5 levels were low, but tended to increase in samples from symptomatic children. These data confirm that the eosinophil product MBP and the eosinophil chemoattractant chemokines RANTES and macrophage-inhibitory protein 1alpha are increased in upper respiratory viral infections associated with asthma exacerbations and suggest an important role for these chemokines in regulating eosinophil influx and activation. These chemokines may represent targets for therapeutic intervention in virus-induced asthma exacerbations.

Asthma↗
PubMed2005

Association of common cold with exacerbations in pediatric but not adult patients with tic disorder: a prospective longitudinal study.

Cross-sectional data and case studies suggest a temporal relationship between fluctuations in tic severity and preceding infections. In this study, we aimed to examine this possible relationship in a prospective longitudinal design. Two groups of tic disorder patients were included, a pediatric group between 7 and 15 years of age (n = 20), and an adult group over 15 years of age (n = 41). During a 24-week period, participants were asked to fill out weekly self questionnaires regarding the presence of tic exacerbations and the experience of the common cold. In addition, 6 throat swabs were taken at monthly intervals and cultured for streptococci; also, 3 serial serum assessments of streptococcal antibodies were performed at 8-week intervals. In the pediatric group, our results indicated a strong association between the self report of a common cold and a symptom exacerbation 4 weeks later (Odds ratio = 4.685; p = 0.001). In the adult group, we found no association between reports of common cold and tic exacerbations. Association with streptococcal infections could not be determined owing to the limited number of observed streptococcal infections. Thus, this study points to a hitherto unknown association of common viral infections with tic exacerbations in children, which may support the involvement of immune dysregulation in tic disorders.

Adolescent↗
PubMed2005

Intravenous versus subcutaneous morphine titration in patients with persisting exacerbation of cancer pain.

BACKGROUND: Patients with cancer pain with initially adequate analgesia under oral sustained-release opioid medication may suffer from persisting pain exacerbations. Sometimes even fast help is needed and then optimally performed by intravenous application (IVA) of immediate-release (IR) opioids. This IVA, however, may only be performed by physicians in Germany. OBJECTIVE: We wanted to find out if subcutaneous application of IR-opioids might be an adequate alternative to IVA in persisting pain exacerbations of patients with cancer pain because this could be performed by the nursing staff in Germany as well. DESIGN: An open randomized controlled trial was used to compare intravenous versus subcutaneous morphine titration in persisting pain exacerbations in patients with cancer pain. SETTING/SUBJECTS: Thirty-nine patients with cancer (21 intravenously, 18 subcutaneously) of the pain management department of the university hospital of Cologne, Germany were included into the study. MEASUREMENTS: Calculated from preexisting analgesic medication boli of morphine were given every 5 minutes (intravenously) or 30 minutes (subcutaneously) up to adequate analgesia or intolerable side effects. Pain intensity, nausea, sedation, and some vital parameters were documented before the start, after each application and at the end of titration. RESULTS: Thirty-five patients were pretreated with oral opioids, 4 patients with nonopioid analgesics. Six patients stopped titration because of intolerable side effects (sedation, vomiting). Thirty patients (77%) reported at least sufficient pain reduction, 3 patients were free of pain (intravenously). Mean pain intensity decreased on a visual analogue scale (VAS, 0-100) from 83 to 32 (intravenously) and from 68 to 42 (subcutaneously). Morphine doses ranged from 4 mg to 32 mg (intravenously; mean, 18.5 +/- 9.2 mg) and from 10 mg to 200 mg (subcutaneously mean, 57.9 +/- 59.6 mg). Mean time up to adequate analgesia was 53 (intravenously) 77 min (subcutaneously), respectively. There was no change in vital parameters but an increase of sedation in both groups. The adaptation of the continuous analgesic medication resulted in a stable and lasting pain relief after 4 days in both groups. CONCLUSIONS: Intravenous and subcutaneous-morphine titration are adequate to antagonize persisting pain exacerbations in cancer pain patients quickly and to adapt the continuous opioid analgesic medication.

Adult↗
PubMed1996

Vitamin A status in acute exacerbations of cystic fibrosis.

Vitamin A is an essential nutrient for epithelial cell maintenance and repair, and it is known that infectious stresses may depress plasma vitamin A concentrations. Patients with cystic fibrosis are at risk for vitamin A deficiency because of fat malabsorption as well as for the inflammatory stresses of pulmonary exacerbations of their underlying disease. We therefore hypothesized that acute pulmonary exacerbations of CF would depress plasma retinol concentrations, and that these concentrations would return to baseline values when clinical symptoms improved. We prospectively studied 35 CF patients (mean age: 24.2 y) consecutively admitted with pulmonary exacerbations. Plasma retinol, vitamin E, retinol binding protein (RBP), and C-reactive protein (CRP) concentrations were measured on hospital admission and discharge. Dietary intake was measured by using a semiquantitative food-frequency questionnaire. Regression analysis was used to identify significant clinical and laboratory correlates of retinol concentrations. On admission, mean (+/- SD) concentrations of plasma retinol were 1.14 +/- 0.5 mumol/L compared with 1.70 +/- 0.6 mumol/L on discharge (P = 0.0001). Of 35 subjects, 8 (22.9%) had plasma retinol concentrations considered to be in the deficient range (< 0.70 mumol/L). Concurrently, mean concentrations of plasma RBP increased during hospital admission (from 1.46 to 2.24 mumol/L, P = 0.003), and the mean CRP concentration declined (from 25.7 to 9.8 mg/L, P = 0.002). Significant positive correlations were found between plasma retinol concentrations at admission and age, weight, body mass index, triceps-skinfold-thickness percentile, midupper arm circumference percentile, plasma vitamin E, and RBP concentration, thus suggesting that better-nourished patients had more optimal vitamin A status. At admission, plasma retinol concentrations were negatively correlated with maximum body temperature and CRP concentrations, which indicated that the body's acute-phase response was associated with the depression in retinol concentrations. We conclude that plasma retinol concentrations are depressed in acute pulmonary exacerbations of cystic fibrosis, and that concentrations considered to be in the deficient range are common. Vitamin A metabolism during acute inflammatory stress deserves further study.

Acute Disease↗
PubMed1978

Infections with viruses and Mycoplasma pneumoniae during exacerbations of chronic bronchitis.

The association of viral and Mycoplasma pneumoniae infections with acute exacerbations of chronic bronchitis was studied by serologic or isolation techniques in 46 adult men during the five years from 1964 through 1968. Serologic evidence of viral or M. pneumoniae infection was detected in 25% of 166 episodes of exacerbation and 14% of 138 remission periods (P = 0.02). Influenza A virus, parainfluenza virus type 3, and coronavirus OC43 predominated; infections with other viruses were infrequent. Infection with M. pneumoniae was detected serologically in four patients, but this organism was never isolated from sputum specimens. Rhinoviruses were isolated from frozen-stored sputum specimens in in 2.7% of the episodes of exacerbation and from 0.55% of the remission intervals (P not significant). These data suggest that although exacerbations of chronic bronchitis may be accompanied by viral and M. pneumoniae infections, patients with chronic bronchitis also acquire such infections without a worsening of their respiratory status.

Adult↗
PubMed1994

Mixed infections of hepatitis C virus as a factor in acute exacerbations of chronic type C hepatitis.

Twenty patients with chronic hepatitis C virus (HCV) infection and acute exacerbations (group A) were studied by polymerase chain reaction with genotype-specific primers to explore the role of mixed infections of HCV in acute exacerbations of chronic type C hepatitis. Another 26 patients who did not have acute exacerbation were matched controls (group B). Eleven (55%) of the group A patients had heterologous HCV, and their mean age was significantly younger than that of the 9 without heterologous infection (55 vs. 67 years, P < .05). In contrast, only 2 group B patients (7.7%) had heterologous HCV infection. In 10 of 13 patients with heterologous HCV infection, type III/2a virus emerged on type II/1b HCV, and viral interference was observed in half of them. The results support that mixed infections of HCV may be important in acute exacerbations of chronic type C hepatitis.

Acute Disease↗
PubMed1999

Infectious exacerbations of chronic bronchitis: diagnosis and management.

Chronic bronchitis is an increasing cause of significant morbidity and mortality. Despite treatment, respiratory tract infection is the most common identifiable cause of death for patients with chronic obstructive pulmonary disease. Repeated infectious exacerbations may ultimately cause acute and chronic lung injury. The most common bacterial aetiologies of acute exacerbations of chronic bronchitis (AECB) include Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae. Pseudomonas aeruginosa is often a nosocomial pathogen and is becoming more prevalent in patients with severe underlying disease. Viruses are responsible for approximately one-third of acute exacerbations overall. Atypical pathogens are causative pathogens in < 10% of episodes. The diagnosis of AECB is often based on clinical impression, although suspicion of bacterial infection can be enhanced by quantitative Gram's stains from appropriately obtained sputum specimens. However, a specific microbiological diagnosis is only needed in certain specific situations. Management of AECB involves non-drug interventions (e.g. smoking cessation) and antibiotic treatment. Recommendations for antibiotic use in patients with known or highly suspected AECB are still evolving. The selection of an antibiotic for treatment of an infectious episode must consider underlying patient co-morbidities, likely pathogens, resistance issues and individual antibiotic properties. Cephalosporins, beta-lactam/beta-lactamase inhibitor combinations and macrolides are all reasonable choices. However, due to the increasing prevalence of resistance to standard antibiotics among common respiratory pathogens, and increased incidence of Pseudomonas spp., fluoroquinolones should be a first-line treatment for AECB in patients who have chronic bronchitis complicated by co-morbid illness, severe obstruction (FEV1 < 50%), old age (> 65 years) or have recurrent exacerbations. In patients who do not have these risk factors (i.e. those with simple chronic bronchitis), agents such as co-trimoxazole remain useful.

Bacterial Infections↗
PubMed2002

Exacerbation by granulocyte colony-stimulating factor of prior acute lung injury: implication of neutrophils.

OBJECTIVE: Granulocyte colony-stimulating factor is widely prescribed to hasten recovery from cancer chemotherapy-induced neutropenia and has been reported to induce pulmonary toxicity. However, circumstances and mechanisms of this toxicity remain poorly known. DESIGN: To reproduce a routine situation in cancer patients receiving chemotherapy, we investigated the mechanisms underlying granulocyte colony-stimulating factor-induced exacerbation of alpha-naphthylthiourea-related pulmonary edema. SETTING: Laboratory research unit. SUBJECTS: Male specific-pathogen-free Sprague-Dawley rats. INTERVENTIONS: The effects of granulocyte colony-stimulating factor given alone or after alpha-naphthylthiourea used to induce acute lung injury were investigated. MEASUREMENTS AND MAIN RESULTS: Lung injury was assessed based on neutrophil sequestration (myeloperoxidase activity in lung tissue) and influx into alveolar spaces (bronchoalveolar lavage fluid cell quantification) and on edema formation (wet/dry lung weight ratio) and alveolar protein concentration into bronchoalveolar lavage fluid. Tumor necrosis factor-alpha and interleukin-1beta were measured in serum, lung homogenates, and isolated alveolar macrophage supernatants. In control rats, granulocyte colony-stimulating factor (25 microg/kg) significantly elevated circulating neutrophil counts without producing alveolar recruitment or pulmonary edema. alpha-Naphthylthiourea significantly increased the wet/dry lung weight ratio (4.68 +/- 0.04 vs. 4.38 +/- 0.07 in controls, p=.04) and induced alveolar protein leakage. Adding granulocyte colony-stimulating factor to alpha-naphthylthiourea exacerbated pulmonary edema, causing neutrophil sequestration in pulmonary vessels, significantly increasing lung myeloperoxidase activity (12.7 +/- 2.0 mOD/min/g vs. 1.1 +/- 0.4 mOD/min/g with alpha-naphthylthiourea alone; p<.0001), and increasing proinflammatory cytokine secretion. alpha-Naphthylthiourea-related pulmonary edema was not exacerbated by granulocyte colony-stimulating factor during cyclophosphamide-induced neutropenia or after lidocaine, which antagonizes neutrophil adhesion to endothelial cells. Tumor necrosis factor-alpha and interleukin-1beta concentrations in alveolar macrophage supernatants and lung homogenates were significantly higher with alpha-naphthylthiourea + granulocyte colony-stimulating factor than with either agent alone, and anti-tumor necrosis factor-alpha antibodies abolished granulocyte colony-stimulating factor-related exacerbation of alpha-naphthylthiourea-induced pulmonary edema. In rats with cyclophosphamide-induced neutropenia, tumor necrosis factor-alpha concentrations in alveolar macrophage supernatants and lung homogenates were significantly decreased compared with rats without neutropenia. CONCLUSION: Granulocyte colony-stimulating factor-related pulmonary toxicity may involve migration of neutrophils to vascular spaces, adhesion of neutrophils to previously injured endothelial cells, and potentiation of proinflammatory cytokine expression.

Animals↗
PubMed1993

Role of infectious agents in exacerbations of ulcerative colitis in India. A study of Clostridium difficile.

Fifty patients with idiopathic ulcerative colitis--25 with acute exacerbation of the disease (Group I) and 25 in quiescent phase (Group II)--were studied. None of the patients had a history of recent exposure to antimicrobial drugs or hospitalization. Evidence of infection with protozoal and bacterial agents and/or presence of Clostridium difficile toxin was demonstrated in eight (32%) patients in group I and one (4%) patient in group II (group I vs. group II, p < 0.05; chi 2 test with Yate's correction). In five of the six patients with demonstrable Clostridium difficile toxin in the stool, one patient with Entamoeba trophozoites, and another with Salmonella infection, the exacerbation responded clinically and endoscopically to specific antimicrobial therapy. Another two patients who had Entamoeba histolytica cysts in the stool had no change in their clinical status with metronidazole. We conclude that infectious agents are responsible for some of the exacerbations in patients of ulcerative colitis in a tropical country like India, where careful microbiologic examination is in order in every acute exacerbation of this disease. This contrasts with the findings in developed countries.

Acute Disease↗
PubMed1992

Association of Epstein-Barr virus infection and pulmonary exacerbations in patients with cystic fibrosis.

We observed severe pulmonary exacerbations during primary Epstein-Barr virus (EBV) infection in adolescent patients with cystic fibrosis. Since EBV is not a known respiratory tract pathogen in cystic fibrosis, we studied retrospectively all EBV-susceptible patients ages 6 to 18 years with chronic Pseudomonas respiratory tract colonization hospitalized for a pulmonary exacerbation during an 18-month period. Patients with serologic evidence of primary EBV infection (n = 5) were compared to control patients without EBV (n = 7). Before admission the groups had similar pulmonary function tests, clinical scores and frequency of hospitalization. On admission patients with EBV had significant weight loss, lower pulmonary function tests and lower clinical scores compared with controls. All remained significantly different 6 months after admission. Frequency of exacerbations requiring hospitalization increased after EBV infection but remained unchanged in controls. Primary EBV infection can be associated with severe pulmonary exacerbations and subsequent deterioration in clinical course in cystic fibrosis patients.

Adolescent↗
PubMed1997

Sequential ciprofloxacin therapy in pediatric cystic fibrosis: comparative study vs. ceftazidime/tobramycin in the treatment of acute pulmonary exacerbations. The Cystic Fibrosis Study Group.

BACKGROUND: Cystic fibrosis patients have chronic bacterial infections of the respiratory tract, most commonly Pseudomonas aeruginosa. Although controversial, administration of antibiotic therapy during acute pulmonary exacerbations is standard practice. Fluoroquinolones are currently not indicated for use in young children because of the observation of arthropathy and damage to growing cartilage in beagle puppies. Because of its activity against P. aeruginosa and excellent oral bioavailability, ciprofloxacin offers a unique therapeutic alternative for this patient population. OBJECTIVE: This prospective, randomized, double blind study compared the efficacy and safety of sequential intravenous/oral ciprofloxacin vs. ceftazidime/tobramycin in hospitalized pediatric cystic fibrosis patients with an acute pulmonary exacerbation associated with P. aeruginosa infection. METHODS: One hundred thirty patients (ages 5 to 17 years) were randomized to receive either i.v. ciprofloxacin 10 mg/kg every 8 h for 7 days followed by oral ciprofloxacin 20 mg/kg every 12 h for a minimum of 3 days or i.v. ceftazidime 50 mg/kg every 8 h plus i.v. tobramycin 3 mg/kg every 8 h for a minimum of 10 days. Clinical, bacteriologic and safety responses were assessed throughout the study. RESULTS: All 84 patients (median age, 11 years; range, 5 to 17 years) valid for efficacy in both treatment groups demonstrated clinical improvement. Five patients experienced clinical relapses (3 ciprofloxacin, 2 ceftazidime/tobramycin) by the 2- to 4-week follow-up. Intent-to-treat analysis demonstrated similar clinical findings between the two treatment groups at both the end of therapy and follow-up. Clinical improvement correlated with improvement in pulmonary function studies and the acute clinical scoring system but not with bacteriologic eradication of Pseudomonas. DNA profiles demonstrated that irrespective of colony morphology, usually one clonal strain was associated with each patient's pulmonary exacerbation. Treatment-associated musculoskeletal events occurred with equal frequency (22% vs. 21%) in both study drug groups (n = 129), and arthralgias were within the range of rates for cystic fibrosis arthropathy. None of these events required study drug discontinuation. CONCLUSION: Sequential i.v./oral ciprofloxacin monotherapy offers a safe and efficacious alternative to standard parenteral therapy for acute pulmonary exacerbations in pediatric cystic fibrosis patients.

Acute Disease↗