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PubMed1985

Management of acute pulmonary exacerbations in cystic fibrosis: a critical appraisal.

Optimal management of acute exacerbations of pulmonary symptoms in patients with cystic fibrosis remains questionable. The underlying cause of such exacerbations has not been identified, and the microbiology of the sputum does not differ substantially during these exacerbations. Despite the absence of conclusive evidence that antibiotic therapy enhances treatment of cystic fibrosis, the consensus favors its use. Various combination and single-agent therapies with aminoglycosides, cephalosporins, and beta-lactam antibiotics are reviewed critically. The importance of high activity against Pseudomonas strains is addressed, as is the potential value of antibiotic prophylaxis. The drawbacks of aminoglycoside treatment are reported. No evidence proves the superiority of combination therapy over monotherapy. Recent results suggesting the effectiveness of monotherapy with piperacillin or ceftazidime are encouraging and deserve follow-up to test continued efficacy and the absence of development of resistant antibiotic strains. Further investigation into the prevention of acute pulmonary exacerbations in cystic fibrosis is essential.

Acute Disease↗
PubMed1999

Comparison of a beta-lactam alone versus beta-lactam and an aminoglycoside for pulmonary exacerbation in cystic fibrosis.

UNLABELLED: We determined whether a beta-lactam and an aminoglycoside have efficacy greater than a beta-lactam alone in the management of a pulmonary exacerbation in patients with cystic fibrosis. STUDY DESIGN: Azlocillin and placebo or azlocillin and tobramycin were administered to 76 patients with a pulmonary exacerbation caused by Pseudomonas aeruginosa in a randomized double-blind, third-party monitored protocol. Improvement was assessed by standardized clinical evaluation, pulmonary function testing, sputum bacterial density, sputum DNA content, and time to the next pulmonary exacerbation requiring hospitalization. RESULTS: No significant difference was seen between the 2 treatment groups in clinical evaluation, sputum DNA concentration, forced vital capacity, forced expiratory volume in second 1, or peak expiratory flow rate at the end of treatment (33 receiving azlocillin alone and 43 both antibiotics); adverse reactions were equivalent in each group. Sputum P. aeruginosa density decreased more with combination therapy (P =.034). On follow-up evaluation, an average of 26 days after the end of treatment, all outcome indicators had worsened in both groups. Time to readmission for a new pulmonary exacerbation was significantly longer in the group receiving azlocillin plus tobramycin (P <.001). Treatment-emergent tobramycin resistance occurred in both groups and was more frequent with combination therapy. CONCLUSION: We conclude that the combination of a beta-lactam and an aminoglycoside produces a longer clinical remission than a beta-lactam alone and slightly better initial improvement.

Adolescent↗
PubMed2003

High levels of urinary pentosidine, an advanced glycation end product, in children with acute exacerbation of atopic dermatitis: relationship with oxidative stress.

Pentosidine is an advanced glycation end product formed by sequential glycation and oxidation. The formation of pentosidine is increased in diseases associated with oxidative stress, such as inflammatory conditions. The aim of the present study was to determine the urinary concentration of pentosidine in atopic dermatitis (AD) and its relationship to the inflammatory status of AD. Urine samples of 32 children with AD and 30 age-matched healthy control subjects were assayed for pentosidine, pyrraline (another advanced glycation end product formed by nonoxidative glycation), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) (an established marker of oxidative stress). Of these 3 markers, urinary concentrations of pentosidine were significantly higher in patients with acute exacerbation of AD than in healthy controls and patients with stable AD. Urinary concentrations of 8-OHdG were significantly higher in AD patients with and without acute exacerbation than in healthy controls. Urinary pentosidine levels correlated significantly with those of 8-OHdG when all data of healthy controls and AD patients were plotted. In patients with acute exacerbation of AD, both urinary pentosidine and 8-OHdG significantly decreased after 7 to 9 days of treatment. Our findings in patients with acute exacerbation of AD suggest that pentosidine levels are partly determined by the prevailing oxidative stress in these patients.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Once daily oral ofloxacin in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation: a randomised placebo-controlled trial.

BACKGROUND: The role of antibiotics in treatment of patients with moderate exacerbations of chronic obstructive pulmonary disease (COPD) is uncertain, but such treatment might be useful in very severe episodes. Our objective was to assess the effects of ofloxacin in patients with exacerbations of COPD who required mechanical ventilation. METHODS: We did a prospective, randomised, double-blind, placebo-controlled trial in 93 patients with acute exacerbation of COPD who required mechanical ventilation. Patients were randomly assigned to receive oral ofloxacin 400 mg once daily (n=47) or placebo (46) for 10 days. Primary endpoints were death in hospital and need for an additional course of antibiotics, both separately and in combination. Analysis was by intention to treat. FINDINGS: Three patients dropped out of the study. Two (4%) patients receiving ofloxacin died in hospital and ten (22%) did so in the placebo group (absolute risk reduction 17.5%, 95% CI 4.3-30.7, p=0.01). Treatment with ofloxacin significantly reduced the need for additional courses of antibiotics (28.4%, 12.9-43.9, p=0.0006). The combined frequency of death in hospital and need for additional antibiotics was significantly lower in patients assigned to ofloxacin than in those receiving placebo (45.9%, 29.1-62.7, p<0.0001). The duration of mechanical ventilation and hospital stay was significantly shorter in the ofloxacin group than in the placebo group (absolute difference 4.2 days, 95% CI 2.5-5.9; and 9.6 days, 3.4-12.8, respectively). INTERPRETATION: New fluoroquinolones, such as ofloxacin, are beneficial in the treatment of COPD exacerbation requiring mechanical ventilation.

Administration, Oral↗
PubMed2002

Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial.

BACKGROUND: Treatment decisions in asthma are based on assessments of symptoms and simple measures of lung function, which do not relate closely to underlying eosinophilic airway inflammation. We aimed to assess whether a management strategy that minimises eosinophilic inflammation reduces asthma exacerbations compared with a standard management strategy. METHODS: We recruited 74 patients with moderate to severe asthma from hospital clinics and randomly allocated them to management either by standard British Thoracic Society asthma guidelines (BTS management group) or by normalisation of the induced sputum eosinophil count and reduction of symptoms (sputum management group). We assessed patients nine times over 12 months. The results were used to manage those in the sputum management group, but were not disclosed in the BTS group. The primary outcomes were the number of severe exacerbations and control of eosinophilic inflammation, measured by induced sputum eosinophil count. Analyses were by intention to treat. FINDINGS: The sputum eosinophil count was 63% (95% CI 24-100) lower over 12 months in the sputum management group than in the BTS management group (p=0.002). Patients in the sputum management group had significantly fewer severe asthma exacerbations than did patients in the BTS management group (35 vs 109; p=0.01) and significantly fewer patients were admitted to hospital with asthma (one vs six, p=0.047). The average daily dose of inhaled or oral corticosteroids did not differ between the two groups. INTERPRETATION: A treatment strategy directed at normalisation of the induced sputum eosinophil count reduces asthma exacerbations and admissions without the need for additional anti-inflammatory treatment.

Adult↗
PubMed2006

Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study.

BACKGROUND: The contributions of as-needed inhaled corticosteroids and long-acting beta2 agonists (LABA) to asthma control have not been fully established. We compared the efficacy and safety of three reliever strategies: a traditional short-acting beta2 agonist; a rapid-onset LABA (formoterol); and a combination of LABA and an inhaled corticosteroid (budesonide-formoterol) in symptomatic patients receiving budesonide-formoterol maintenance therapy. METHODS: We did a 12-month, double-blind, parallel-group study in 3394 patients (aged 12 years or older), in 289 centres in 20 countries, who were using inhaled corticosteroids at study entry and symptomatic on budesonide-formoterol (160 microg and 4.5 microg, respectively), one inhalation twice daily, during a 2-week run-in. After run-in, patients were randomly assigned budesonide-formoterol maintenance therapy plus one of three alternative as-needed medications-terbutaline (0.4 mg), formoterol (4.5 microg), or budesonide-formoterol (160 microg and 4.5 microg). The primary outcome was time to first severe exacerbation, defined as an event resulting in hospitalisation, emergency room treatment, or both, or the need for oral steroids for 3 days or more. FINDINGS: Time to first severe exacerbation was longer with as-needed budesonide-formoterol versus formoterol (p=0.0048; log-rank test) and with as-needed formoterol versus terbutaline (p=0.0051). The rate of severe exacerbations was 37, 29, and 19 per 100 patients per year with as-needed terbutaline, formoterol, and budesonide-formoterol, respectively (rate ratios budesonide-formoterol versus formoterol 0.67 [95% CI 0.56-0.80; p<0.0001]; budesonide-formoterol versus terbutaline 0.52 [0.44-0.62; p<0.0001]; formoterol versus terbutaline 0.78 [0.67-0.91; p=0.0012]). Asthma control days increased to a similar extent in all treatment groups. As-needed formoterol did not significantly improve symptoms compared with as-needed terbutaline. All treatments were well tolerated. INTERPRETATION: Both monocomponents of budesonide-formoterol given as needed contribute to enhanced protection from severe exacerbations in patients receiving combination therapy for maintenance.

Adolescent↗
PubMed1998

Home treatment of exacerbations of chronic obstructive pulmonary disease by an acute respiratory assessment service.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease are a major cause of hospital admissions, but do not require intensive investigation or complex therapy. We investigated the suitability of home care for severe uncomplicated exacerbations. METHODS: Over 3.5 years we assessed 962 patients with exacerbations of chronic obstructive pulmonary disease after referral to a hospital respiratory department by their family physicians. All patients had chest radiographs, oxygen-saturation or arterial-gas analysis, spirometry, and physical assessment. Unless admission was thought to be essential, patients were allowed home with a customised treatment package. Each patient was visited daily by a respiratory nurse who monitored progress and treatment compliance and provided education and reassurance. FINDINGS: 145 (15%) of 962 required admission at initial referral and 115 (12%) were admitted later. 653 (68%) patients were managed entirely at home and 49 (5%) were referred inappropriately. One patient died at home. All patients had severe disease with a mean forced expiratory volume in 1 s of 1.02 L and 395 (41%) had required hospital admission in the previous year. INTERPRETATION: After formal assessment in a hospital respiratory unit, many patients with exacerbations of chronic obstructive pulmonary disease can be treated at home by respiratory nurses.

Acute Disease↗
PubMed2003

A comparison of 5-day courses of dirithromycin and azithromycin in the treatment of acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Short-term use of antibiotics has become a common component of the management of acute exacerbations of chronic bronchitis (AECB), particularly in complex cases with productive cough or purulent phlegm. The macrolide antibiotics, particularly second-generation agents such as dirithromycin and azithromycin, are among the antibiotic classes frequently recommended and used to treat upper and lower respiratory infections, including AECB. OBJECTIVE: This study compared the clinical efficacy and tolerability of 5-day courses of dirithromycin and azithromycin given once daily for the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: This randomized, investigator-blinded, parallel-group clinical trial was conducted at 5 centers in the United States. Eligible patients were adult (age >35 years) smokers or ex-smokers (smoking history of at least 10 pack-years) with chronic bronchitis and an acute exacerbation, defined by the occurrence of increased dyspnea and/or productive cough and feverishness within 48 hours of enrollment. Before randomization, an attempt was made to obtain a sputum specimen from each patient for Gram's staining and culture. Patients were randomized to receive dirithromycin 500 mg QD for 5 days or azithromycin 500 mg QD on day 1 and 250 mg QD on days 2 to 5. Clinical efficacy was assessed separately by patients and physicians at early (days 7-10) and late (days 25-35) posttreatment visits. RESULTS: Eighty-six patients (48 women, 38 men; mean age, 55 years) with a mean smoking history of 31 pack-years were included in the intent-to-treat analysis. Forty-six (54%) patients were randomized to dirithromycin and 40 (47%) patients to azithromycin. Clinical efficacy was reported in a high proportion of patients in both treatment groups, both at the early posttreatment visit (84.8% dirithromycin, 75.7% azithromycin; difference dirithromycin - azithromycin, 9.1%; 95% CI, -8.2 to 26.4) and the late posttreatment visit (95.5% and 86.5%, respectively; difference dirithromycin - azithromycin, 9.0%; 95% CI, -3.7 to 21.6). A similar proportion of patients required a second course of antibiotics over the study period (20.5% dirithromycin, 27.0% azithromycin; difference dirithromycin - azithromycin, -6.6%; 95% CI, -25.2 to 12.1). Only 42 (48.8%) patients were able to produce a sputum sample before receiving study treatment, and of these, only 20 (47.6%) demonstrated a preponderance of neutrophils on Gram's staining. Both treatments were well tolerated. CONCLUSIONS: The results of this study suggest comparable clinical efficacy between 5-day courses of once-daily dirithromycin and azithromycin in acute exacerbations of COPD. There were insufficient data to permit meaningful comparison of the bacteriologic efficacy of these macrolide antibiotics.

Acute Disease↗
PubMed2003

Placebo-controlled trials do not find association of olanzapine with exacerbation of bipolar mania.

BACKGROUND: Published case reports describe apparent induction or exacerbation of manic-like symptoms during treatment with the atypical antipsychotics olanzapine and risperidone. To date, such reports are from uncontrolled clinical experience and therefore cannot clarify whether the atypical antipsychotics caused such manic-like states or simply failed to prevent them. Presumably, bipolar patients would be at increased risk for this putative adverse event. Therefore, we evaluated the potential of olanzapine to exacerbate symptoms of mania compared to placebo during treatment of bipolar mania. METHODS: Two inpatient, double-blind, randomized trials investigating the efficacy of olanzapine 5-20 mg daily versus placebo for the treatment of acute mania were combined. Two hundred and fifty-four subjects participated (placebo n=129; olanzapine n=125) in the two studies. Severity of mania was quantified with the 11-item Young-Mania Rating Scale (Y-MRS). In a post-hoc analysis, after double-blind therapy up to 3 weeks, categorical comparison of olanzapine and placebo groups was made for any worsening and worsening by 10 or 20% from baseline Y-MRS scores (LOCF). RESULTS: The percentage of subjects with exacerbation at endpoint were: any worsening, placebo 37.7%, olanzapine 21.8% (P=0.005); >or=10% worsening, placebo 24.6%, olanzapine 14.5% (P=0.039); >or=20% worsening, placebo 15.6%, olanzapine 8.1% (P=0.064). CONCLUSION: Mania rating scores worsened for some patients during olanzapine therapy. However, this was significantly less common with olanzapine than with placebo. These controlled data suggest that clinical case reports of occurrence of 'mania' during treatment with olanzapine, and possibly those with other atypical antipsychotics, reflect exacerbation in the natural history of bipolar illness, rather than an adverse pharmacological effect. LIMITATIONS: Post-hoc analysis of pooled data from two different studies.

Adult↗
PubMed2003

Clinical outcome and virologic profiles of severe hepatitis B exacerbation due to YMDD mutations.

BACKGROUND/AIMS: To study the outcome and the virologic profiles of severe hepatitis exacerbations due to YMDD mutants in lamivudine-treated patients. METHODS: Eighteen lamivudine-treated patients with severe hepatitis exacerbations due to YMDD mutants were recruited. Laboratory and clinical parameters were monitored. Viral genotypes and YMDD mutations were determined. RESULTS: None of the 18 patients had YMDD wild-type during exacerbations. Three (17%) and 15 (83%) patients had genotypes B and C, respectively. Elevated bilirubin levels and prolonged prothrombin time were found in 11 (61%) and six patients (33%) respectively. Three patients (17%) had adverse outcome with the development of ascites and/or encephalopathy. One of these patients required liver transplantation and one died. Both patients had evidence of cirrhosis before treatment and hepatitis B e antigen (HBeAg) seroreversion from anti-HBe positivity. The remaining 16 patients (89%) have no evidence of pre-existing cirrhosis. Thirty seven percent of patients had normal alanine aminotransferase levels at the last follow-up. The median HBV DNA level at the last follow-up was significantly lower than the pre-treatment level (P=0.009). CONCLUSIONS: Though the majority of patients with severe hepatitis exacerbations due to YMDD mutants had uneventful course, early liver transplantation should be considered in patients with pre-existing cirrhosis and HBeAg seroreversion.

Adult↗
PubMed1996

Sequential changes in full-length genomes of hepatitis B virus accompanying acute exacerbation of chronic hepatitis B.

BACKGROUND/AIM: During the course of persistent hepatitis B virus infection, viral replication markedly decreases after acute exacerbation of liver inflammation accompanied by emergence of antihepatitis B e antibody (anti-HBe) and/or anti-hepatitis B surface antibody (anti-HBs). In some cases, however, persistent viral replication continues even after such exacerbation with or without HBeAg/anti-HBe seroconversion. The aim of the present study was to investigate the extent of genetic variations of HBV in this phenomenon. METHODS: Full-length HBV genomes were amplified by polymerase chain reaction from sera of three patients before and after acute exacerbation and were directly sequenced. RESULTS: In the whole genomes of 3215 nucleotides, only six nucleotide mutations for six amino acid substitutions (2 in the surface gene, 2 in the X gene, 1 in the core gene and 1 in the polymerase gene) were observed in patient 1, 15 mutations for 14 amino acid substitutions (1 in the pre-core codon 28, 4 in the surface gene, 4 in the core gene and 5 in the polymerase gene) were observed in patient 2, and 5 mutations for 6 amino acid substitutions (2 in the surface gene, 2 in the X gene, pre-core stop codon mutation and 1 in the polymerase gene) were observed in patient 3. Substitution in the a determinant of the surface gene, which encodes target epitopes for neutralizing antibodies, as well as those in the pre-core/core gene, which encodes epitopes for cytotoxic T cells, were mainly found. CONCLUSION: HBV that remained after the emergence of anti-HBe and anti-HBs are considered to possess mutations in epitopes for both humoral and cellular immunity. These mutant HBV may be involved in the pathogenesis of persistent hepatic injury after acute exacerbation.

Adult↗
PubMed1999

The role of ipratropium bromide in the emergency management of acute asthma exacerbation: a metaanalysis of randomized clinical trials.

STUDY OBJECTIVE: This study was conducted to determine whether the addition of inhaled ipratropium to inhaled beta-agonist therapy is effective in the treatment of adults with acute asthma exacerbation. METHODS: Published reports of randomized, controlled trials assessing the use of ipratropium and beta-agonists in asthma were identified by a search of the MEDLINE, EMBASE, CINAHL, Biological Abstracts on CD, the Cochrane Library, and Current Contents databases. Bibliographies from identified studies and from review articles were manually searched. Published and unpublished reports in English, French, and Italian were identified and assessed for inclusion in the metaanalysis. Randomized, double-blind, placebo-controlled trials were selected in which ipratropium was used as adjunctive therapy to beta-agonists in adult patients with acute asthma exacerbation presenting to a hospital emergency department or similar acute care setting. Data were extracted independently by 2 reviewers. For eligible trials, the mean percent change in peak expiratory flow rate (PEFR), or forced expiratory volume in one second (FEV1), and their SDs were assessed in the ipratropium-treated and control groups. The effect of ipratropium on hospitalization rates and adverse effects were also analyzed. RESULTS: Data from 10 studies, reporting on a total of 1,377 patients with asthma, were pooled using a weighted average method. Compared with placebo, the use of ipratropium was associated with a pooled 7.3% improvement in FEV1 (95% confidence interval [CI] 3.8% to 10.9%), corresponding to an absolute improvement in FEV1 in the ipratropium/ beta-agonist group, which was 100 mL (95% CI 50 to 149 mL) above that seen for the group that received beta-agonist without ipratropium. Similarly, the pooled estimate of treatment effect in trials that reported data as PEFR was 22.1% (95% CI 11.0% to 33.2%), corresponding to an absolute peak expiratory flow improvement of 32 L/min (95% CI 16 to 47 L/min) in favor of the ipratropium/ beta-agonist combination group. When these data were combined using effect size as a common measure, the use of ipratropium was associated with a summary effect size of.38 (95% CI.27 to.48). Effect sizes were negatively correlated with baseline mean expiratory flows, suggesting that studies enrolling patients with more severe airflow obstruction showed greater absolute benefits of combination bronchodilator therapy. For the 3 trials reporting hospital admission data (n=1,031), patients receiving ipratropium had a relative risk of hospitalization of .73 (95% CI.53 to .99). The use of ipratropium was not associated with any severe adverse effects when used in conjunction with beta2 -agonists. CONCLUSION: There is a modest statistical improvement in airflow obstruction when ipratropium is used as an adjunctive treatment to beta2 -agonists for the treatment of acute asthma exacerbation. Although the clinical significance of this improvement in airflow obstruction remains unclear, it would seem reasonable to recommend the use of combination ipratropium/ beta-agonist therapy in acute adult asthmatic exacerbations, since the addition of ipratropium seemed to provide physiologic evidence of benefit without risk of adverse effects.

Acute Disease↗
PubMed1997

Self-treatment by adults during slow-onset exacerbations of asthma.

Self-management plans are considered today an essential component of the management of asthma. The objective of the present study was (a) to explore patients' present practical knowledge of self-treatment of asthma, and (b) to provide an assessment of the effect of an educational program on this knowledge and self-treatment behaviour. Twenty four adults with asthma from the outpatient clinic of the Department of Pulmonary Medicine participated in a self-management program. They were provided with explanations on the symptoms and precipitating factors of their asthma, on its treatment with medication and their side-effects, and with personal written guidelines for self-adjustment of their medication. Prior to the program their practical knowledge of adequate self-treatment was investigated using a hypothetical scenario of a slow-onset asthma exacerbation. The effectiveness of the teaching and training program was evaluated by the change in knowledge prior to and 5 months after the program and self-reported behaviour of the participants at follow-up. (a) More than 60% of the patients lacked practical knowledge of self-treatment of a slow-onset exacerbation of asthma. (b) The educational program resulted in a significant increase (47%) of this knowledge. (c) Actual self-treatment behaviour, as recorded by the patients 5 months after completing the educational program, was adequate in only two of ten patients, who experienced an exacerbation during the study period. Many adults with asthma are deficient in practical knowledge of self-treatment of a slow-onset exacerbation. This knowledge was significantly augmented by an educational program. Nevertheless actual self-treatment behaviour at follow-up was inadequate in the majority of patients.

Acute Disease↗
PubMed2003

Bacterial infections in patients requiring admission for an acute exacerbation of COPD; a 1-year prospective study.

STUDY OBJECTIVE: To investigate the frequency of respiratory bacterial infections in hospitalized patients, admitted with an acute exacerbation of chronic obstructive pulmonary disease (COPD), to identify the responsible pathogens by sputum culture and to assess patient characteristics in relation to sputum culture results. METHODS: We prospectively evaluated clinical data and sputum culture results of 171 patients, admitted to the pulmonology department of the University Hospital Maastricht with an acute exacerbation of COPD from 1st January 1999 until 31st December 1999. RESULTS: Eighty-five patients (50%) had positive sputum cultures, indicating the presence of bacterial infection. Pathogens most frequently isolated were: Haemophilus influenzae (45%), Streptococcus pneumoniae (27%), and Pseudomonas aeruginosa (15%). Patients with more severely compromised lung function had a higher incidence of bacterial infections (P = 0.026). There were no significant differences in age, lung function parameters, blood gas results and length of hospital stay between patients with and without bacterial infection. There were no correlations between the type of bacteria isolated and clinical characteristics. CONCLUSION: Incidence of bacterial infection during acute exacerbations of COPD is about 50%. Patients with and without bacterial infection are not different in clinical characteristics or in outcome parameters. Patients with lower FEV1 have a higher incidence of bacterial infections, but there is no difference in the type of bacterial infection. In the future, the pathogenic role of bacterial infection in exacerbations of COPD should be further investigated, especially the role of bacterial infection in relation to local and systemic inflammation.

Acute Disease↗
PubMed2006

Intranasal ketorolac challenge for the diagnosis of aspirin-exacerbated respiratory disease.

BACKGROUND: Intranasal administration of aspirin-lysine has been used in Europe for the diagnosis of aspirin-exacerbated respiratory disease. It has a low adverse effect profile and is believed to be safer for asthmatic patients, particularly those with a low baseline forced expiratory volume in 1 second, in whom oral aspirin challenge would be contraindicated. Ketorolac, a nonsteroidal anti-inflammatory drug useful for severe pain, is available in the United States in parenteral form. OBJECTIVE: To determine whether ketorolac nasal challenge has acceptable specificity and sensitivity for diagnosing aspirin-exacerbated respiratory disease. METHODS: Twenty-nine patients with suspected aspirin-exacerbated respiratory disease were challenged with nasal ketorolac before oral challenge and desensitization with aspirin. Symptoms, objective changes in nasal examination findings, and peak nasal inspiratory flow values were recorded. Nasal lavage fluid for cysteinyl leukotriene analysis was collected. Ketorolac doses of 2.1, 5.2, or 7.8 mg were administered and compared with the results of oral aspirin challenge. RESULTS: Eighteen patients had a positive challenge reaction to oral aspirin. Ketorolac nasal inhalation had a sensitivity of 78% and a specificity of 64%. Patients in the reactor group had significantly higher levels of cysteinyl leukotrienes after ketorolac challenge than in the nonreactor group. Mild bronchospasm occurred in 3 patients, and 2 of these occurred at higher starting doses of ketorolac. CONCLUSIONS: Nasal ketorolac administration is a reasonably accurate and safe method for diagnosing aspirin-exacerbated respiratory disease.

Administration, Intranasal↗
PubMed2003

Relationship of outdoor air quality to pediatric asthma exacerbations.

BACKGROUND: Although exposure to outdoor air pollutants has been shown to be associated with exacerbations of asthma, there are relatively few admissions for asthma to Cincinnati Children's Hospital, Cincinnati, OH during the summer months when air quality tends to be worst. OBJECTIVE: The objective of this study was to determine the relationship of outdoor air quality parameters to asthma exacerbations in children. METHODS: The number of emergency room visits and hospitalizations for asthma were determined by review of emergency department logs and the hospital computer database. Outdoor air concentrations of ozone, particulates of < 10 microm diameter (PM-10), pollens, and fungal spores were obtained from the Hamilton County Department of Environmental Services. Multiple regression analysis was performed, looking for relationships between the daily number of asthma visits and the air quality data for the same day and for 1 through 5 days before the visits. RESULTS: A significant association was found between the number of asthma visits and the daily pollen count (P = 0.014, SE = 0.001). The effect was stronger for visits 1, 2, and 3 days after the pollen count (P < 0.001 for pollen count lagged 3 days). High PM-10 counts were synergistic with the pollen count as a predictor of asthma visits. There was no association between asthma visits and the ozone concentration or fungal spore count. CONCLUSIONS: Exacerbations of asthma severe enough to require visits to the hospital were associated with elevated concentrations of airborne pollens and particulates, with a significant delayed effect. Ozone, in the concentrations measured here, was not a risk factor for severe asthma exacerbations in children.

Air Pollutants↗
PubMed2003

Treatment of acute exacerbations of COPD.

Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death in the United States, is increasing worldwide and is projected to be the third leading cause of death in the United States by the year 2020 (1). It affects nearly 16 million Americans, and more than $18 billion is spent annually on medications, physician visits, and hospitalizations. COPD is characterized by chronic airflow obstruction with episodic acute exacerbations, which result in increased morbidity and mortality. Patients hospitalized with exacerbations have an overall mortality rate of 3% to 4%, and up to 24% of patients requiring care in the intensive care unit die (2). Since forced expiratory volume in 1 second correlates closely with life expectancy and exacerbation rate, early diagnosis (through spirometric testing) and prevention may reduce acute exacerbations and health care costs.

Acute Disease↗
PubMed2006

[Bacterial etiology of chronic bronchitis exacerbations treated by primary care physicians].

OBJECTIVE: Few studies have been carried out to determine the prevalence of microorganisms causing exacerbations of chronic bronchitis in the community setting. The aim of the present study was to determine the bacterial etiology of chronic bronchitis exacerbations in patients not requiring hospitalization. PATIENTS AND METHODS: This observational, cross-sectional, multicenter study was carried out at the primary care level during 2 weeks (in November 2001 and January 2002). All laboratory work was carried out at a single center. We studied 1,947 patients with mild-moderate exacerbations treated by 650 primary care physicians. All the sputum samples received for centralized processing were subject to Gram staining, microscopic examination, and bacterial culture. RESULTS: Out of 1,537 cultures of sputum samples collected, 498 had good cell quality for microscopic examination (32.4%). Of the 498 good quality samples analyzed, 246 (49.4%) were positive and 468 isolates were obtained. The most commonly isolated germ was Streptococcus pneumoniae (163 cases, 34.8%), followed by Moraxella catarrhalis (112, 23.9%), and Haemophilus influenzae (59, 12.6%). In 1.2% of the S. pneumoniae isolates resistance was found to amoxicillin; resistance to macrolides was found in 34.3%. The antibiotics most commonly prescribed, however, were macrolides (38.3% of the prescriptions). CONCLUSIONS: S. pneumoniae was the microorganism most frequently isolated in cases of chronic bronchitis exacerbation treatable in this outpatient setting.

Acute Disease↗