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Role of viruses in exacerbations of chronic obstructive pulmonary disease.

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Respiratory viral infections, especially rhinoviruses, are a major cause of COPD exacerbations, with upper respiratory tract infections being associated with over 50% of COPD exacerbations. The presence of an upper respiratory tract infection leads to a more severe exacerbation and a longer symptom recovery time at exacerbation. Respiratory viral infections occurring during COPD exacerbations are more likely to lead to hospitalization. Sputum inflammatory markers were found to be higher in those patients with symptoms of a common cold or where rhinovirus was detected at exacerbation, thus suggesting that viral infections lead to greater airway inflammation and thus more severe exacerbations. COPD exacerbations are associated also with systemic inflammatory effects with increases in markers such as plasma fibrinogen and interleukin-6. Respiratory viruses have also been detected when the patients are stable, and this suggests that chronic viral infection may occur. Strategies to prevent viral infection will have a significant effect on the morbidity of COPD and will improve quality of life.

Common Cold↗

Which patients with acute exacerbation of chronic obstructive pulmonary disease benefit from noninvasive positive-pressure ventilation? A systematic review of the literature.

BACKGROUND: Over the past decade, noninvasive positive-pressure ventilation (NPPV) in the setting of acute exacerbations of chronic obstructive pulmonary disease (COPD) has increased in popularity. Although several trials have been published on the relative effectiveness of this treatment, apparent inconsistencies in study results remain. PURPOSE: To assess the effect of NPPV on rate of endotracheal intubation, length of hospital stay, and in-hospital mortality rate in patients with an acute exacerbation of COPD and to determine the effect of exacerbation severity on these outcomes. DATA SOURCES: MEDLINE (1966 to 2002) and EMBASE (1990 to 2002). Additional data sources included the Cochrane Library, personal files, abstract proceedings, reference lists of selected articles, and expert contact. There were no language restrictions. STUDY SELECTION: The researchers selected randomized, controlled trials that 1) examined patients with acute exacerbation of COPD; 2) compared noninvasive ventilation and standard therapy with standard therapy alone; and 3) included need for endotracheal intubation, length of hospital stay, or hospital survival as an outcome. DATA EXTRACTION: Methodologic quality and results were abstracted independently and in duplicate. DATA SYNTHESIS: The addition of NPPV to standard care in patients with an acute exacerbation of COPD decreased the rate of endotracheal intubation (risk reduction, 28% [95% CI, 15% to 40%]), length of hospital stay (absolute reduction, 4.57 days [CI, 2.30 to 6.83 days]), and in-hospital mortality rate (risk reduction, 10% [CI, 5% to 15%]). However, subgroup analysis showed that these beneficial effects occurred only in patients with severe exacerbations, not in those with milder exacerbations. CONCLUSIONS: Patients with severe exacerbations of COPD benefit from the addition of NPPV to standard therapy. However, NPPV has not been shown to benefit hospitalized patients with milder COPD exacerbations.

Hospital Mortality↗

Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) frequently develop exacerbations, leading to major clinical and health resource use ramifications. OBJECTIVE: To prospectively evaluate the effectiveness of a long-acting inhaled anticholinergic bronchodilator, tiotropium, in reducing COPD exacerbations and exacerbation-related health care utilization. DESIGN: Randomized, double-blind study. SETTING: 26 Veterans Affairs medical centers. PATIENTS: 1829 patients with moderate to severe COPD (mean baseline FEV(1), 36% predicted). INTERVENTION: Once-daily tiotropium (18 microg) or placebo for 6 months. Patients otherwise received usual care, except for other anticholinergic bronchodilators. MEASUREMENTS: The coprimary end points were the percentage of patients with a COPD exacerbation and the percentage of patients with a COPD-related hospitalization. RESULTS: Tiotropium significantly reduced the percentage of patients experiencing 1 or more exacerbations compared with placebo (27.9% vs. 32.3%, respectively; difference, -5.7 percentage points [95% CI, -10.4 to -1.0 percentage points]; P = 0.037). Fewer tiotropium patients were hospitalized because of COPD exacerbation (7.0% vs. 9.5%, respectively; difference, -3.0 percentage points [CI, -5.9 to -0.1 percentage points]; P = 0.056), although this difference was of borderline statistical significance. Analysis of secondary outcomes indicates that tiotropium may lengthen the time to first COPD exacerbation (P = 0.028) and reduce health care utilization for exacerbations, including the frequency of hospitalizations (P = 0.047), unscheduled clinic visits (P = 0.019), and days of antibiotic treatment (P = 0.015). Tiotropium did not statistically significantly reduce all-cause hospitalization rates. LIMITATIONS: Trial participants were enrolled from 1 health care system, and 99% were men. The follow-up period extended for only 6 months. CONCLUSIONS: Tiotropium reduces COPD exacerbations and may reduce related health care utilization in patients with moderate to severe COPD.

Administration, Inhalation↗

C-reactive protein levels during disease exacerbations and infections in systemic lupus erythematosus: a prospective longitudinal study.

We prospectively studied the value of measuring C-reactive protein (CRP) levels in patients with systemic lupus erythematosus (SLE) to distinguish between disease exacerbation and infection. During a 2 year followup of 71 lupus patients, 38 episodes of disease exacerbation and 36 episodes of infection could be analyzed. Plasma samples were obtained at least once a month. CRP levels were increased (greater than 6 mg/l) during 25 of the 38 exacerbations and during 32 of the 36 infections. Median CRP levels during infection (60 mg/l; range 1-400) were higher than during disease exacerbation (16.5 mg/l; range 1-375) (p less than 0.05). Levels of CRP rose prior to the exacerbation (p less than or equal to 0.01) and fell afterwards (p less than or equal to 0.01). During exacerbations accompanied by serositis, median levels of CRP (76 mg/l; range 2-375) were higher than during exacerbations without serositis (16 mg/l; range 1-53) (p less than 0.02). CRP levels exceeding 60 mg/l during exacerbations without serositis indicated infection in all cases. Thus, measurement of CRP in SLE is valuable to distinguish between infection and exacerbation only in the absence of serositis.

Adolescent↗

Pharmacological management to reduce exacerbations in adults with asthma: a systematic review and meta-analysis.

CONTEXT: Over the last 2 decades, many new pharmacological agents have been introduced to reduce the growing morbidity associated with asthma, but the long-term effects of these agents on exacerbations are unclear. OBJECTIVE: To systematically review and quantitatively synthesize the long-term effects of inhaled corticosteroids, long-acting beta2 agonists, leukotriene pathway modifiers/receptor antagonists, and anti-IgE therapies on clinical outcomes and particular clinically relevant exacerbations in adult patients with chronic asthma. DATA SOURCES: MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant randomized controlled trials and systematic reviews published from January 1, 1980, to April 30, 2004. We identified additional studies by searching bibliographies of retrieved articles and contacting experts in the field. STUDY SELECTION AND DATA EXTRACTION: Included trials were double-blind, had follow-up periods of at least 3 months, and contained data on exacerbations and/or forced expiratory volume in 1 second. The effects of interventions were compared with placebo, short-acting beta2 agonists, or each other. DATA SYNTHESIS: Inhaled corticosteroids were most effective, reducing exacerbations by nearly 55% compared with placebo or short-acting beta2 agonists (relative risk [RR], 0.46; 95% confidence interval [CI], 0.34-0.62; P<.001 for heterogeneity). Compared with placebo, the use of long-acting beta2 agonists was associated with 25% fewer exacerbations (RR, 0.75; 95% CI, 0.64-0.88; P =.43 for heterogeneity); when added to inhaled corticosteroids, there was a 26% reduction above that achieved by steroid monotherapy (RR, 0.74; 95% CI, 0.61-0.91; P =.07 for heterogeneity). Combination therapy was associated with fewer exacerbations than was increasing the dose of inhaled corticosteroids (RR, 0.86; 95% CI, 0.76-0.96; P =.65 for heterogeneity). Compared with placebo, leukotriene modifiers/receptor antagonists reduced exacerbations by 41% (RR, 0.59; 95% CI, 0.49-0.71; P =.44 for heterogeneity) but were less effective than inhaled corticosteroids (RR, 1.72; 95% CI, 1.28-2.31; P =.91 for heterogeneity). Use of monoclonal anti-IgE antibodies with concomitant inhaled corticosteroid therapy was associated with 45% fewer exacerbations (RR, 0.55; 95% CI, 0.45-0.66; P =.15 for heterogeneity). CONCLUSIONS: Inhaled corticosteroids are the single most effective therapy for adult patients with asthma. However, for those unable or unwilling to take corticosteroids, the use of leukotriene modifiers/receptor agonists appears reasonable. Long-acting beta2 agonists may be added to corticosteroids for those who remain symptomatic despite low-dose steroid therapy. Anti-IgE therapy may be considered as adjunctive therapy for young adults with asthma who have clear evidence of allergies and elevated serum IgE levels.

Adrenergic beta-Antagonists↗

Measurement of increases in anti-double-stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus. A long-term, prospective study.

To evaluate the predictive power of changes in levels of antibodies to double-stranded DNA (anti-dsDNA) as a predictor of disease exacerbations in systemic lupus erythematosus (SLE), we performed a prospective study on 72 unselected patients with SLE (mean duration of study 18.5 months, range 6-35 months). Patients were seen at least once every 3 months, and disease activity was scored according to a specific protocol. Plasma samples were obtained at least once every month and were assessed for anti-dsDNA antibody (by the Crithidia luciliae assay, an enzyme-linked immunosorbent assay [ELISA], and the Farr assay) and for complement components C3 and C4. Twenty-seven of 33 disease exacerbations observed during the study period were accompanied by a positive test result for anti-dsDNA antibody (27 by the Farr assay, 19 by the C luciliae assay, and 23 by the ELISA). Twenty-four of these exacerbations were preceded by a significant increase in anti-dsDNA antibody levels (23 by the Farr assay, 12 by the C luciliae assay, and 17 by the ELISA). The first observance of a significant increase in anti-dsDNA antibody levels preceded the exacerbation by 8-10 weeks. Significant increases in anti-dsDNA antibody levels not followed by an exacerbation were observed in 5 cases by the Farr assay, in 7 cases by the C luciliae assay, and in 3 cases by the ELISA; however, in 3 cases, 2 cases, and 1 case, respectively, these increases were followed by an increase in disease activity that did not fulfill the criteria for an exacerbation. Serial measurement of anti-dsDNA antibody levels was more sensitive for predicting exacerbations than was measurement of C3 and/or C4 levels (P less than 0.03). Serial assessment of anti-dsDNA antibody levels, especially by the Farr assay, is a sensitive and reasonably specific method for predicting disease exacerbations in SLE.

Adolescent↗

Acute exacerbation in chronic type B hepatitis: comparison between HBeAg and antibody-positive patients.

The incidence, clinicopathological features and etiology of acute exacerbation occurring in patients with chronic type B hepatitis were assessed prospectively among 385 patients who had HBeAg and 279 who had anti-HBe in serum. During an average follow-up of 23.5 months, acute exacerbations occurred in 197 HBeAg-positive patients and in 56 anti-HBe positive patients, with a calculated annual incidence of 28.6 and 10.3%, respectively (p less than 0.001). The clinical and laboratory findings of acute exacerbations were similar in the HBeAg-positive and anti-HBe positive patients. The mean serum bilirubin and alpha-fetoprotein levels were higher in anti-HBe positive patients (p less than 0.01), but actual differences were small. The histologic features of acute exacerbations were also similar in the HBeAg-positive patients and anti-HBe positive patients. Lobular alterations were the main histologic findings; in addition, one-fourth of patients had bridging necrosis and one-fourth had piecemeal necrosis. Spontaneous reactivation of hepatitis B was the major cause of these exacerbations in both HBeAg-positive patients (91.5%) as well as anti-HBe positive patients (62.5%). Hepatitis delta virus superinfection accounted for a higher percentage of exacerbations in anti-HBe positive patients (14.3%) than in HBeAg-positive cases (6.5%). Hepatitis A and possibly non-A, non-B virus superinfections also contributed to some episodes of exacerbation. Thus, acute exacerbations of disease occurred more frequently in HBeAg-positive patients than in anti-HBe positive patients with chronic type B hepatitis, but the clinicopathological features and etiologies were similar.

Acute Disease↗

Acute exacerbation and hepatitis B virus clearance after emergence of YMDD motif mutation during lamivudine therapy.

Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication, but its long-term use may be associated with HBV tyrosine-methionine-aspartate-aspartate (YMDD) motif mutation. To examine the clinical features and course after emergence of YMDD mutants, 55 patients who received lamivudine therapy over 104 weeks at our unit were assayed for YMDD mutation(s). Thirty-two of them were found to have the YMDD mutation. They continued lamivudine therapy and were followed up weekly or biweekly if clinically indicated. Thirty (93.7%) of them showed elevation of alanine transaminase (ALT), and 13 (40.6%) experienced acute exacerbation at 4 to 94 weeks (median, 24 weeks) after emergence of the YMDD mutant. The incidence of exacerbation is much higher than 4.3% in patients without the YMDD mutation (P =.003). Compared with patients without exacerbation, patients with exacerbation had a significantly higher serum HBV-DNA level after emergence of the YMDD mutant (P <.005). Before exacerbation, serum HBV-DNA level was rising to its peak, followed by the peaking of ALT (247-2,010 U/L) 1 to 4 weeks later. Three patients developed hepatic decompensation, but then in association with hepatitis B e antigen (HBeAg) seroconversion, recovered. Of the 12 evaluable patients, 8 (75%) showed HBeAg seroconversion, and 3 showed mutant clearance within 1 to 5 months after exacerbation. In contrast, none of the patients without exacerbation showed HBeAg seroconversion (P <.001). These results indicate that acute exacerbations may occur after emergence of the YMDD mutation. The incidence, clinicopathological features, and subsequent course, and possibly the underlying immune mechanisms, are similar to those of wild-type HBV chronic infection. Because severe hepatitis may occur, patients should be followed carefully once the YMDD mutant emerges.

Adolescent↗

Defining an exacerbation of pulmonary disease in cystic fibrosis.

Despite the importance of pulmonary exacerbations in CF in both clinical and research settings, both published evidence and consensus are lacking concerning the criteria used to define an exacerbation. The use of hospitalization as a surrogate measure presupposes uniformity among clinicians in diagnosis and treatment of exacerbations. Our aims were to evaluate consensus among clinicians about the variables considered helpful in diagnosing an exacerbation requiring treatment. A comprehensive list of symptoms, signs, and investigations used to define exacerbations was compiled from published trials. A written self-administered questionnaire included the list in age-appropriate groups to survey opinion about the helpfulness of each item, and the estimated proportion of patients admitted within a month of diagnosis of an exacerbation. This was sent to all clinicians managing CF patients in Australia. There were replies from 59/91 clinicians (65%), 41/60 (68%) from those managing children and 18/31 (58%) from those managing adults. Responses of those managing children and adults differed for 7/32 variables (Mann-Whitney test, P < 0.05). Clinic grouping did not show greater consensus among responses of pediatricians (Kruskal-Wallis test, P = 0.362). Consensus, >74% or <26% of respondents rating a variable helpful/very helpful, was found in only 50% of variables listed. Estimated admission rate within a month of diagnosis was 61% (30-100%) for those managing adults and 48% %5-100%) for pediatricians. A lack of consensus was found among clinicians managing CF about the variables considered in diagnosing an exacerbation. The estimated proportion admitted within a month of diagnosis was very variable. This demonstrated inhomogeneity in approach to diagnosis and management of an exacerbation suggests a significant heterogeneity of clinical care.

Adolescent↗

Abnormalities of renal endothelin during acute exacerbation in chronic obstructive pulmonary disease.

Circulating and urinary levels of endothelin (ET), an endothelium-derived vasoconstrictive and mitogenic peptide have been reported to increase in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms of these abnormalities are not fully understood. Our study objectives were to evaluate pulmonary and renal ET clearance in COPD patients during an acute exacerbation. Our participants included nine consecutive patients with moderate to severe COPD without signs of right heart failure admitted for acute exacerbation and ten healthy volunteers (HV) as controls. ET was detected by radioimmunoassay in venous and arterial blood as well as in a timed urine specimen. For each subject, arterial/venous immunoreactive ET ratio (ir-ETart/ir-ETven) was evaluated as an index of its pulmonary clearance. Creatinine clearance was employed in each case to obtain a corrected renal ir-ET clearance. Glomerular filtration rate (GFR) was also assessed by dynamic(99m)Tc-diethylenetriamine pentaacetic acid renal scintigraphy in six COPD patients during acute exacerbation and at recovery. The ratio ir-ETart/ir-ETven was comparable in COPD patients (0.75+/-0.12) and in HV (0.82+/-0.09). A significant difference was found with respect to 24 h ir-ET urinary excretion between COPD patients during exacerbation as well as at recovery (respectively 142.1+/-12.8 ng/24 h and 89.0+/-15.1 ng/24 h) and HV (65.1+/-10.1 ng/24 h). ET renal clearance was higher in COPD patients than in HV (29.2+/-5.2 ml min(-1)in COPD during exacerbation; 17.5+/-3.9 ml min(-1)at recovery and 13.6+/-2.4 ml min(-1)in HV, P<0.001). GFR was 69.4+/-10.0 ml min(-1)in COPD patients during exacerbation and it significantly increased at the recovery (95.5+/-20.9 ml min(-1)P<0.001). Corrected renal clearance of the peptide was significantly correlated to GFR values during the exacerbation (r=-0.81, P<0.05). Furthermore change in renal ET production resulted associated with changes in paCO(2)(r=0.83, P<0.001) and in paO(2)(r=-0.73, P<0.05). Acute exacerbation in COPD patients causes an increase in renal ET production which is partially reversible at the recovery, in the absence of significant changes in ET-1 circulating levels. ET might contribute to the renal response to hypoxaemia and hypercapnia in COPD.

Acute Disease↗

The Role of Antibiotics in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Our understanding of the pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD) has increased considerably in the past decade. Several new lines of evidence support bacterial causation of about half the exacerbations. Contrary to previous data, recent studies with improved methodology have demonstrated that exacerbations do contribute to the loss of lung function in COPD. Another interesting new observation is that colonization by bacterial pathogens may not be innocuous, and in fact may lead to airway inflammation and contribute to pathogenesis of COPD. Evidence that bacteria cause exacerbations, that exacerbations contribute to loss of lung function, and that chronic colonization by bacteria may be harmful, has emphasized the potential importance of appropriate antibiotics in the treatment of exacerbations. An unfortunate paucity of data does not allow evidence-based recommendations to be made for optimal choice of antibiotics for exacerbations of COPD. Emerging data that antibiotics differ in unconventional measures of efficacy such as time to next exacerbation, improvement in health-related quality of life, and bacteriologic eradication will help us make concrete recommendations in the future.

Journal Article↗

Rises in anti-double stranded DNA antibody levels prior to exacerbations of systemic lupus erythematosus are not merely due to polyclonal B cell activation.

We investigated whether rises in anti-double stranded DNA (anti-ds DNA) antibody levels prior to disease exacerbations of systemic lupus erythematosus (SLE) are part of a restricted immune response or merely the consequence of polyclonal B cell activation. As possible inducers of polyclonal B cell activation, we analyzed, in addition, the role of clinically apparent infections in relation to changes in levels of anti-ds DNA and disease exacerbations. We prospectively followed 72 lupus patients who were examined for disease activity and infections at least every 3 months by history and physical examination according to a protocol. Once a month, we measured levels of IgG-class antibodies to an unrelated recall antigen (tetanus toxoid), levels of IgG-class antibodies to a viral antigen (cytomegalovirus late antigens [CMV-LA]), levels of total immunoglobulins G and M, and levels of anti-ds DNA (by ELISA and Farr assay). Thirty-three exacerbations and 31 infections were observed during a follow-up period of an average of 18.5 patient months. Twenty-four out of the 27 exacerbations accompanied by a positive test for anti-ds DNA were preceded by a significant rise in anti-ds DNA: in 17 cases by ELISA and in 22 cases by Farr assay. These 24 rises in levels of anti-ds DNA prior to the exacerbation were paralleled by a significant rise in levels of IgG-class anti-tetanus antibodies in 8 cases, anti-CMV-LA antibodies in 9 cases, total IgG in 7 cases, and total IgM in 15 cases. Median rise in anti-ds DNA, as measured both by ELISA and Farr assay, exceeded the median rise in anti-tetanus antibodies, anti-CMV-LA antibodies, and total IgG and IgM (P less than 0.0001). Only one infection was recorded within a period of 3 months prior to an exacerbation, whereas infections never occurred within a period of 3 months prior to a rise in anti-ds DNA. We conclude that rises in anti-ds DNA prior to exacerbations of SLE are largely due to preferential activation of anti-ds DNA-specific B cells and not merely to polyclonal B cell hyperactivity. Clinically significant infections are not related to rises in levels of anti-ds DNA nor to the induction of exacerbations in SLE.

Adolescent↗

Defining COPD exacerbations: impact on estimation of incidence and burden in primary care.

AIMS: To investigate the impact of definition on the incidence of chronic obstructive pulmonary disease (COPD) exacerbations in primary care. METHODS: In a one-year prospective, observational study, data from diary cards were used to determine the incidence of symptom- and healthcare-defined exacerbations. One hundred and twenty seven patients completed > or =80% of days in the diary card and were included in the analysis. RESULTS: Incidence of COPD exacerbation varied according to definition. Mean yearly rates were 2.3 for symptom- and 2.8 for healthcare-defined exacerbations. Although patients with FEV(1) <50% had a higher mean yearly rate of healthcare-defined exacerbations than those with FEV(1) > or =50% (3.2 vs 2.3; p=0.003), patients with less severe disease reported recurrent exacerbations. There was limited agreement between symptom- and healthcare-defined exacerbations. CONCLUSION: Lung function does not appear to be a valid criterion for assigning COPD management directed at patients with recurrent exacerbation.

Aged↗

Characterisation of patients with frequent exacerbation of asthma.

BACKGROUND: Exacerbation is one of the most significant problems in patients with asthma. Although subpopulation of patients is more susceptible to exacerbations than others, which clinical features characterise susceptibility to exacerbation are not well understood. METHODS: Consecutive non-smoking adult patients with asthma who had multiple exacerbations (ME) despite regular maintenance treatment were compared with those who had at most single exacerbation as control during the previous 1 year. Exacerbation of asthma is defined initiations or escalations of systemic corticosteroid as part of the management for aggravated asthma condition. RESULTS: Patients with ME (n=32, male: 6, mean age: 46.7 years) were characterised by intensive current maintenance treatment (dose of inhaled corticosteroid; 1037.5+/-452.8 vs 621.6+/-257.3 microg, P=0.0005, proportion of oral corticosteroid users; 28.1% vs 2.7%, P=0.008), severe episodes of exacerbation (asthma-related hospitalisations; 71.9% vs 23.4%, P=0.0002, arrival on ambulance; 37.5% vs 8.1%, P=0.008), concomitant chronic sinusitis (34.4% vs 10.8%, P=0.038) and intolerance to non-steroidal anti-inflammatory drugs (NSAIDs) (34.4% vs 5.4%, P=0.006) in comparison with controls (n=37, male:11, mean age:44.4). Pulmonary function in patients with ME was characterised by persistent airflow limitation and reduced reversibility. CONCLUSION: Patients with ME are at increased risk for severe exacerbation despite more intensive maintenance anti-inflammatory treatment. Persistent irreversible airflow limitation and complications of chronic sinusitis and/or NSAIDs intolerance are characteristics to this subpopulation.

Adrenal Cortex Hormones↗

Medication compliance and disease exacerbation in patients with asthma: a retrospective study of managed care data.

BACKGROUND: Compliance with asthma medications probably results in improved outcomes, but few studies have examined this relationship. OBJECTIVE: To examine the association between medication compliance and exacerbation in asthmatic patients. METHODS: Retrospective analysis of a managed care database. The 97,743 participants (aged 6-99 years; mean age, 32.8 years) had asthma and prescriptions for controller medications. Compliance with the index medication (the first controller medication prescribed) was measured using 2 methods: medication possession ratio (MPR), calculated for 365 days after the index date, and number of prescriptions for each index medication. Exacerbation was defined as 1 or more emergency department visits or hospitalizations within 1 year of the index date. Multivariate models were used to determine the odds of exacerbation based on relative compliance for each definition of compliance. RESULTS: Based on the median MPR, more-compliant patients were less likely to experience exacerbation than less-compliant patients (odds ratio, 0.94; 95% confidence interval, 0.91-0.97; P < .001). Using the 75th percentile MPR, risk of exacerbation was even smaller (odds ratio, 0.89; 95% confidence interval, 0.86-0.92; P < .001). All the cutoff points for compliance (> or = 2 through > or = 6 prescriptions) demonstrated significantly less exacerbations in more-compliant vs less-compliant patients after adjusting for covariates. As the criteria for compliance became more stringent, more-compliant patients became increasingly less likely to have an exacerbation vs less-compliant patients. CONCLUSION: More-compliant asthmatic patients were significantly less likely to experience exacerbation than less-compliant asthmatic patients. These findings demonstrate the importance of improving medication compliance among asthmatic patients to impact outcomes.

Adolescent↗

Perception of dyspnea during exacerbation and histamine-related bronchoconstriction in patients with asthma.

BACKGROUND: Numerous studies have been performed concerning the perception of dyspnea during changes in airway caliber provoked in the laboratory setting, but studies of asthma exacerbation are scarce. OBJECTIVE: To investigate whether the perception of dyspnea during histamine-induced bronchoconstriction might be used to identify patients with asthma who sense dyspnea poorly during exacerbation. METHODS: The perception of dyspnea in 50 patients (45 female, 5 male) with asthma was evaluated at admission with exacerbation and during a stable period. Perceived intensity of dyspnea was estimated using a modified Borg scale. The perception of dyspnea in the stable period 4 to 6 weeks after exacerbation was measured with the histamine challenge test. Perception parameters were defined as the change in Borg score divided by the change in forced expiratory volume in 1 second (FEV1) as a percentage of the baseline FEV1 (deltaBorg/deltaFEV1) and as the Borg score at 20% decrease (PS20Histamine) or increase (PS20Exacerbation) in FEV1. RESULTS: The perception of dyspnea during asthma exacerbation was unrelated to the perception of dyspnea during histamine-induced bronchoconstriction (for deltaBorg/deltaFEV1, beta = .08, P = .50; for PS20, beta = -.11, P = .40). The kappa value for the agreement of poor perceivers at exacerbation and during the stable period was -0.21 (P = .10). However, the intensity of dyspnea caused by histamine-induced bronchoconstriction was lower than that caused by asthma exacerbation (PS20: 1.6 +/- 1.1 vs 2.8 +/- 2.5, respectively, P = .004; deltaBorg/deltaFEV1: 0.08 +/- 0.05 vs 0.21 +/- 0.28, respectively, P = .001). CONCLUSION: The perception of dyspnea during asthma exacerbation is not correlated with the perception of dyspnea during histamine-induced bronchoconstriction. Therefore, the perception of dyspnea during histamine-induced bronchoconstriction cannot be used to identify the asthmatic patients who perceive dyspnea poorly.

Adult↗

Costs of asthma in a cohort of Swiss adults: associations with exacerbation status and severity.

OBJECTIVE: This article will address the effect of exacerbation status, disease severity (defined by medication required), and other variables on resource use and costs for asthma in Switzerland in 1996 to 1997. METHODS: A retrospective chart-based study was performed. A sample of 422 adults was analyzed. Target variables were stratified by disease severity and exacerbation status. Bivariate associations were assessed. Multiple linear regression was performed on the logarithm of direct medical costs. RESULTS: The probability of exacerbations was positively associated with disease severity. Resource use and costs were associated with both of these variables. Multiple linear regression identified age, presence of asthma-related comorbidities, degree of severity, exacerbation status, quick reliever versus controller therapy, and diagnosis or treatment by a pulmonologist as independent influences on direct costs. An interaction between severity and exacerbation status was also noted. Regression identified direct costs in the highest severity group to be 2.5 times higher than those in the lowest group, if there were no exacerbations. If exacerbations were present, costs were 5.7 times higher. CONCLUSIONS: Because of its high prevalence, asthma has a high impact on public health. This impact depends on disease severity and, according to these findings, may also depend on the extent to which exacerbations are avoided or at least controlled.

Acute Disease↗

Practical evaluation of asthma exacerbation self-management in children and adolescents.

The objective of this study was to describe asthma exacerbation self-management in children and adolescents. We used a cross-sectional study population enrolled in the International Study of Asthma and Allergies in Childhood (ISAAC) in Bordeaux. Subjects answered an additional questionnaire on utilization of health services, self-evaluation of usual asthma exacerbation severity and home management of asthma exacerbation. Criteria used for selecting patients were both having asthma confirmed by a physician and having had suffered from symptoms during the past year. Children and adolescents attended similar health services for managing their asthma but compliance to anti-asthmatic treatment was better in children than in adolescents. Among the children 4.8% had asthma and 6.2% of adolescents had asthma, as diagnosed by a doctor. Of the children, 72.3% and of the adolescents 54.7% had less than one asthma attack per month. In cases of mild asthma exacerbation, 38.7% of adolescents and 9.3% of children waited until the end of exacerbation without taking any medication. The proportion of children not receiving any treatment was lower when symptoms were more severe but this was not the case in adolescents. Although most of the patients used were taking beta2-agonist, we found that 21-43% of children or adolescents did not receive appropriate medication in the event of asthma exacerbation. These results demonstrate that (i) asthma exacerbation self-management is related to self-assessed severity of symptoms and that (ii) a large proportion of asthmatic children in the community, and particularly adolescents, do not therefore receive appropriate treatment in the event of asthma exacerbation.

Acute Disease↗