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PubMed2002

Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by both an accelerated decline in lung function and periods of acute deterioration in symptoms termed exacerbations. The aim of this study was to investigate whether these are related. METHODS: Over 4 years, peak expiratory flow (PEF) and symptoms were measured at home daily by 109 patients with COPD (81 men; median (IQR) age 68.1 (63-74) years; arterial oxygen tension (PaO(2)) 9.00 (8.3-9.5) kPa, forced expiratory volume in 1 second (FEV(1)) 1.00 (0.7-1.3) l, forced vital capacity (FVC) 2.51 (1.9-3.0) l); of these, 32 (29 men) recorded daily FEV(1). Exacerbations were identified from symptoms and the effect of frequent or infrequent exacerbations (> or < 2.92 per year) on lung function decline was examined using cross sectional, random effects models. RESULTS: The 109 patients experienced 757 exacerbations. Patients with frequent exacerbations had a significantly faster decline in FEV(1) and peak expiratory flow (PEF) of -40.1 ml/year (n=16) and -2.9 l/min/year (n=46) than infrequent exacerbators in whom FEV(1) changed by -32.1 ml/year (n=16) and PEF by -0.7 l/min/year (n=63). Frequent exacerbators also had a greater decline in FEV(1) if allowance was made for smoking status. Patients with frequent exacerbations were more often admitted to hospital with longer length of stay. Frequent exacerbations were a consistent feature within a patient, with their number positively correlated (between years 1 and 2, 2 and 3, 3 and 4). CONCLUSIONS: These results suggest that the frequency of exacerbations contributes to long term decline in lung function of patients with moderate to severe COPD.

Administration, Inhalation↗
PubMed2006

Asthma exacerbations during pregnancy: incidence and association with adverse pregnancy outcomes.

Exacerbations of asthma during pregnancy represent a significant clinical problem and may be related to poor pregnancy outcomes. A systematic review of the literature was conducted for publications related to exacerbations during pregnancy. Four studies with a control group (no asthma) and two groups of women with asthma (exacerbation, no exacerbation) were included in meta-analyses using fixed effects models. During pregnancy, exacerbations of asthma which require medical intervention occur in about 20% of women, with approximately 6% of women being admitted to hospital. Exacerbations during pregnancy occur primarily in the late second trimester; the major triggers are viral infection and non-adherence to inhaled corticosteroid medication. Women who have a severe exacerbation during pregnancy are at a significantly increased risk of having a low birth weight baby compared with women without asthma. No significant associations between exacerbations during pregnancy and preterm delivery or pre-eclampsia were identified. Inhaled corticosteroid use may reduce the risk of exacerbations during pregnancy. Pregnant women may be less likely to receive oral steroids for the emergency management of asthma. The effective management and prevention of asthma exacerbations during pregnancy is important for the health of both the mother and fetus.

Asthma↗
PubMed2001

Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.

The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV(1), 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD.

Aged↗
PubMed2002

Exacerbations of chronic obstructive pulmonary disease: when are bacteria important?

The progressive course of chronic obstructive pulmonary disease (COPD) is often aggravated by exacerbations, the majority of them produced by bronchial infection. Frequent exacerbations have been demonstrated to have a negative impact on quality of life and pulmonary function in patients with COPD, particularly in active smokers. Furthermore, acute exacerbations are the most frequent cause of medical visits, hospital admissions and death among patients with chronic lung disease. Evidence indicates that the number of patients with pathogenic bacteria in respiratory secretions and the bronchial bacterial load increase during exacerbations. Furthermore, the local inflammatory response of the host parallels the increase in bacterial load. From these observations, it can be speculated that, for symptoms of acute exacerbation to appear, there must be a minimum bacterial load in the airways, i.e. a threshold above which the inflammatory reaction is severe enough to elicit clinical symptoms of exacerbation. This threshold may vary from patient to patient owing to different modifying factors. Some of these factors may be the recognised risk factors for relapse, such as increasing age, impairment of lung function, comorbid conditions or frequent exacerbations in the past. Relapse rates after ambulatory treatment of acute exacerbation of COPD may be as high as 20-25% of cases. Relapses are associated with significant mordibity and increased costs. A number of unanswered questions remain regarding exacerbations of chronic obstructive pulmonary disease. These include the role of viral infection, the importance of residual bacterial colonisation and the impact of new antibiotics on the treatment of exacerbations.

Acute Disease↗
PubMed2005

MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation.

BACKGROUND: Irreversible airflow obstruction in Chronic Obstructive Pulmonary Disease (COPD) is thought to result from airway remodelling associated with aberrant inflammation. Patients who experience frequent episodes of acute deterioration in symptoms and lung function, termed exacerbations, experience a faster decline in their lung function, and thus over time greater disease severity However the mechanisms by which these episodes may contribute to decreased lung function are poorly understood. This study has prospectively examined changes in sputum levels of inflammatory cells, MMP-9 and TIMP-1 during exacerbations comparing with paired samples taken prior to exacerbation. METHODS: Nineteen COPD patients ((median, [IQR]) age 69 [63 to 74], forced expiratory volume in one second (FEV1) 1.0 [0.9 to 1.2], FEV1% predicted 37.6 [27.3 to 46.2]) provided sputa at exacerbation. Of these, 12 were paired with a samples collected when the patient was stable, a median 4 months [2 to 8 months] beforehand. RESULTS: MMP-9 levels increased from 10.5 microg/g [1.2 to 21.1] prior to exacerbation to 17.1 microg/g [9.3 to 48.7] during exacerbation (P < 0.01). TIMP-1 levels decreased from 3.5 microg/g [0.6 to 7.8] to 1.5 microg/g [0.3 to 4.9] (P = 0.16). MMP-9/TIMP-1 Molar ratio significantly increased from 0.6 [0.2 to 1.1] to 3.6 [2.0 to 25.3] (P < 0.05). Neutrophil, eosinophil and lymphocyte counts all showed significant increase during exacerbation compared to before (P < 0.05). Macrophage numbers remained level. MMP-9 levels during exacerbation showed highly significant correlation with both neutrophil and lymphocyte counts (Rho = 0.7, P < 0.01). CONCLUSION: During exacerbation, increased inflammatory burden coincides with an imbalance of the proteinase MMP-9 and its cognate inhibitor TIMP-1. This may suggest a pathway connecting frequent exacerbations with lung function decline.

Aged↗
PubMed2006

Markers of exacerbation severity in chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can experience 'exacerbations' of their conditions. An exacerbation is an event defined in terms of subjective descriptors or symptoms, namely dyspnoea, cough and sputum that worsen sufficiently to warrant a change in medical management. There is a need for reliable markers that reflect the pathological mechanisms that underlie exacerbation severity and that can be used as a surrogate to assess treatment effects in clinical studies. Little is known as to how existing study variables and suggested markers change in both the stable and exacerbation phases of COPD. In an attempt to find the best surrogates for exacerbations, we have reviewed the literature to identify which of these markers change in a consistent manner with the severity of the exacerbation event. METHODS: We have searched standard databases between 1966 to July 2004 using major keywords and terms. Studies that provided demographics, spirometry, potential markers, and clear eligibility criteria were included in this study. Central tendencies and dispersions for all the variables and markers reported and collected by us were first tabulated according to sample size and ATS/ERS 2004 Exacerbation Severity Levels I to III criteria. Due to the possible similarity of patients in Levels II and III, the data was also redefined into categories of exacerbations, namely out-patient (Level I) and in-patient (Levels II & III combined). For both approaches, we performed a fixed effect meta-analysis on each of the reported variables. RESULTS: We included a total of 268 studies reported between 1979 to July 2004. These studies investigated 142,407 patients with COPD. Arterial carbon dioxide tension and breathing rate were statistically different between all levels of exacerbation severity and between in out- and in-patient settings. Most other measures showed weak relationships with either level or setting, or they had insufficient data to permit meta-analysis. CONCLUSION: Arterial carbon dioxide and breathing rate varied in a consistent manner with exacerbation severity and patient setting. Many other measures showed weak correlations that should be further explored in future longitudinal studies or assessed using suggested mathematical modelling techniques.

Arteries↗
PubMed2007

Risk indexes for exacerbations and hospitalizations due to COPD.

OBJECTIVE: The ability to predict exacerbations in patients with COPD might permit more rational use of preventive interventions. Our objective was to develop risk indexes for exacerbations and hospitalizations due to exacerbations that might be applied to the individual patient. METHODS: Spirometry, demographics, and medical history were obtained at baseline in 1,829 patients with moderate-to-very severe COPD who entered a trial of inhaled tiotropium. Information about exacerbations and hospitalizations due to exacerbation was collected during the 6-month follow-up period. Analyses of first outcomes were modeled using univariable and multivariable Cox proportional hazards regressions. RESULTS: During follow-up, 551 patients had at least one exacerbation and 151 patients had at least one hospitalization due to exacerbation. In the multivariable model for exacerbation, older age, percentage of predicted FEV(1), duration of COPD, a productive cough, antibiotic or systemic corticosteroid use for COPD in the prior year, hospitalization for COPD in the prior year, and theophylline use at baseline predicted a higher risk. In the multivariable model for hospitalization, older age, percentage of predicted FEV(1), unscheduled clinic/emergency department visits for COPD in the prior year, any cardiovascular comorbidity, and prednisone use at baseline were associated with greater risk. Both the exacerbation and the hospitalization models provided moderately good discrimination, the validated concordance indexes being 0.66 and 0.73, respectively. Methods for calculating risk in individual patients are provided. CONCLUSIONS: Spirometry along with a few questions directed to the patient are strongly predictive of exacerbations and related hospitalizations over the ensuing 6 months.

Aged↗
PubMed2000

Acute exacerbation of COPD: factors associated with poor treatment outcome.

OBJECTIVES: To determine the effect of age, severity of lung disease, severity and frequency of exacerbation, steroid use, choice of an antibiotic, and the presence of comorbidity on the outcome of treatment for an acute exacerbation of COPD. DESIGN: A retrospective chart analysis over 24 months. SETTING: A university Veterans Affairs medical center. PATIENTS: Outpatients with COPD who were treated with an antibiotic over a period of 24 months for an acute exacerbation of COPD. METHODS: Severity of an acute exacerbation of COPD was defined using the criteria of Anthonisen et al: increased dyspnea, increased sputum volume, and increased sputum purulence. Severity of lung disease was stratified based on FEV(1) percent predicted using American Thoracic Society guidelines (stage I, FEV(1) > or = 50%; stage II, FEV(1) 35 to 49%; stage III, FEV(1) < 35%). Treatment outcome was judged successful when the patient had no return visit in 4 weeks for a respiratory problem. Failure was defined as a return visit for persistent respiratory symptoms that required a change of an antibiotic in < 4 weeks. RESULTS: One-hundred seven patients with COPD (mean age +/- SD, 66.9 +/- 9.5 years) experienced 232 exacerbations over 24 months. First-line antibiotics (trimethoprim-sulfamethoxazole, ampicillin/amoxicillin, and erythromycin) were used to treat 78% of all exacerbations. Treatment failure was noted in 12.1% of first exacerbations and 14. 7% of all exacerbations, with more than half the failures requiring hospitalization. Host factors that were independently associated with treatment failure included the following: FEV(1) < 35% (46.4% vs 22.4%; p = 0.047), use of home oxygen (60.7% vs 15.6%; p < 0. 0001), frequency of exacerbation (3.8 +/- 2.0 vs 1.6 +/- 0.91; p < 0. 001), history of previous pneumonia (64.3% vs 35.1 p < 0.007), history of sinusitis (28.6% vs 8.8%; p < 0.009) and use of maintenance steroids (32.1% vs 15.2% p = 0.052). Using stepwise logistic regression analysis to identify the top independent variables, the use of home oxygen (p = 0.0002) and frequency of exacerbation (p < 0.0001) correctly classified failures in 83.3% of the patients. Surprisingly, age, the choice of an antibiotic, and the presence of any one or more comorbidity did not affect the treatment outcome. CONCLUSION: The results of our study suggest that patient host factors and not antibiotic choice may determine treatment outcome. Prospective studies in appropriately stratified patients are needed to validate these findings.

Acute Disease↗
PubMed2001

Mild exacerbations and eosinophilic inflammation in patients with stable, well-controlled asthma after 1 year of follow-up.

OBJECTIVES: To determine the time to exacerbation and probability of a mild exacerbation of asthma, and the impact of eosinophilic inflammation on these parameters in patients with stable, well-controlled asthma. PATIENTS AND METHODS: A cohort of 31 patients with stable, well-controlled asthma receiving inhaled steroid treatment regularly were followed up for 1 year or until a mild exacerbation occurred. Mild exacerbation was defined as symptoms of asthma lasting > 48 h with a fall in peak expiratory flow > 20%. FEV(1), provocative concentration of methacholine causing a 20% fall in FEV(1), eosinophil count, and eosinophilic cationic protein (ECP) levels in blood and in sputum were measured at the first visit and every 2 months. RESULTS: At baseline, the mean (SD) eosinophil count was 0.39 x 10(9)/L (0.21 x 10(9)/L) in blood and 13% (14%) in sputum; ECP was 30 microg/L (28 microg/L) in blood and 75 microg/L (85 microg/L) in sputum. Thirteen subjects experienced a mild exacerbation during the 1-year follow-up period. The mean time to mild exacerbation was 293 days (95% confidence interval [CI], 248 to 337 days), and the cumulative probability of not experiencing a mild exacerbation in 1 year was 49% (95% CI, 39 to 59%). An increased risk of mild exacerbation was associated with blood eosinophil count > 0.4 x 10(9)/L (relative risk 4.5; 95% CI of relative risk, 1.8 to 38.0), blood ECP > 20 microg/L (relative risk, 2.1; 95% CI of relative risk, 1.0 to 9.2), and sputum ECP > 40 microg/L (relative risk, 2.5; 95% CI of relative risk, 1.2 to 11.2), but was unassociated with other variables. CONCLUSIONS: Patient with stable, well-controlled asthma are at risk of mild exacerbation during 1 year of follow-up despite regular inhaled steroid treatment. Eosinophilic inflammation expressed as eosinophil count and ECP is associated with higher risk of mild exacerbation.

Administration, Inhalation↗
PubMed2004

Exacerbations and progression of disease in asthma and chronic obstructive pulmonary disease.

Exacerbations, characterized by an increase in patients' symptoms above baseline, are characteristic of both chronic obstructive pulmonary disease (COPD) and asthma. Prevention of exacerbations and their expedient treatment are major goals for reducing the morbidity and cost of both conditions. Exacerbations, however, may also adversely affect the natural history of these disorders, perhaps by contributing to increased rates of lung function decline, systemic effects, and premature mortality. Although the available information is limited, the course of COPD is affected adversely by exacerbations in multiple ways. First, exacerbations likely lead to structural alterations in the lung and to permanently worsened airflow. Second, health status is adversely affected by exacerbations, and although the mechanisms are unclear, the effects are long lasting and may be irreversible. Less is known in asthma about the effect of exacerbations on natural history, but many of the same pathogenetic processes involved in COPD exacerbations likely play a role in some subjects with asthma as well. Future studies of how exacerbation affects the "natural history" of asthma and COPD will require a better understanding of the heterogeneity of exacerbations but promises to identify new therapeutic strategies to treat these disorders.

Asthma↗
PubMed2005

Role of antimicrobial agents in the management of exacerbations of COPD.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a common occurrence and characterize the natural history of the disease. Over the past decade, new knowledge has substantially enhanced our understanding of the pathogenesis, outcome and natural history of AECOPD. The exacerbations not only greatly reduce the quality of life of these patients, but also result in hospitalization, respiratory failure, and death. The exacerbations are the major cost drivers in consumption of healthcare resources by COPD patients. Although bacterial infections are the most common etiologic agents, the role of viruses in COPD exacerbations is being increasingly recognized. The efficacy of antimicrobial therapy in acute exacerbations has established a causative role for bacterial infections. Recent molecular typing of sputum isolates further supports the role of bacteria in AECOPD. Isolation of a new strain of Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae was associated with a considerable risk of an exacerbation. Lower airway bacterial colonization in stable patients with COPD instigates airway inflammation, which leads to a protracted self-perpetuating vicious circle of progressive lung damage and disease progression. A significant proportion of patients treated for COPD exacerbation demonstrate incomplete recovery, and frequent exacerbations contribute to decline in lung function. The predictors of poor outcome include advanced age, significant impairment of lung function, poor performance status, comorbid conditions and history of previous frequent exacerbations requiring antibacterials or systemic corticosteroids. These high-risk patients, who are likely to harbor organisms resistant to commonly used antimicrobials, should be identified and treated with antimicrobials with a low potential for failure. An aggressive management approach in complicated exacerbations may reduce costs by reducing healthcare utilization and hospitalization.

Anti-Bacterial Agents↗
PubMed2026

[Microbiological Characterization of Exacerbations in Severe Asthma and Their Impact on Therapeutic Decision-Making].

INTRODUCTION: Severe asthma (SA) exacerbations impose a substantial healthcare burden. Microbiological characterization using molecular techniques may improve pathogen identification and contribute to a more individualized therapeutic approach. OBJECTIVE: To characterize the microbiological profile of exacerbations in patients with severe asthma and to analyze the prescription patterns for antibiotics (ATB) and systemic corticosteroids (SC). METHODS: This retrospective observational study was conducted in a Severe Asthma Unit. A total of 103 exacerbations were investigated using conventional microbiological methods and multiplex polymerase chain reaction (FilmArray&#x2122;) performed on respiratory samples. Bacterial findings were classified according to operational criteria compatible with infection or colonization based on genomic load and culture results. Associations between clinical, microbiological, and therapeutic variables were explored using univariate analyses. RESULTS: Microbiological detection was achieved in 78.6% of exacerbations. Viruses were identified in 59.2% of episodes, with rhinovirus representing the predominant pathogen (62.3% of viral detections). Bacteria were identified in 53.4% of exacerbations (H. influenzae 36,6%), frequently in association with viral coinfection. Bronchiectasis was associated with a higher probability of bacterial detection (OR 2.50; p&#xa0;=&#xa0;0.031). ATB and SC were prescribed in 61.2% and 44.6% of exacerbations, respectively, with frequent use of combination therapy. No significant differences in overall microbiological detection rates were observed according to biologic therapy status. Considerable microbiological variability was observed across recurrent exacerbations in the same patient. CONCLUSIONS: Microbiological findings were common during severe asthma exacerbations, with respiratory viruses, particularly rhinovirus, being the most frequently identified pathogens. Bronchiectasis was associated with higher rates of bacterial detection and ATB use. The marked variability observed between episodes supports the potential value of individualized microbiological assessment during exacerbations and warrants prospective studies aimed at optimizing therapeutic decision-making.

Biologic therapies.↗
PubMed2000

Haemophilus influenzae oral vaccination against acute bronchitis.

OBJECTIVES: To assess the effects of an oral whole cell nontypeable Haemophilus influenzae (NTHi) vaccine in protecting against recurrent episodes of bronchitis. SEARCH STRATEGY: We searched the Cochrane trials register, MEDLINE, Extramed, ISI Current Contents, Carl Uncover and contacted investigators of the studies. SELECTION CRITERIA: Randomised trials comparing the effects of an oral monobacterial NTHi vaccine on patients with recurrent exacerbations of bronchitis were included when there was overt matching of the vaccine and placebo groups on clinical grounds. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed trial quality independently from original records and publications for incidence and severity of bronchitis episodes and carriage rate of nontypeable Haemophilus influenzae in the upper respiratory tract every three months following vaccination. MAIN RESULTS: Six trials were included in the study with a total of 440 participants. Oral vaccination using a monobacterial whole cell killed nontypeable Haemophilus influenzae significantly reduced the incidence of bronchitic episodes at 3 months (Weighted Mean Difference [WMD] 6.694; 95% confidence interval [CI] 6.963 - -6.424; p < 0.01) and 6 months (WMD 4.496; 95% CI 4.664 - -4.327; p < 0.01) following vaccination. The effect diminished by 9 months. The severity of exacerbations in the treatment group was likewise reduced by 58% at 3 months (Peto OR = 0. 42; 95% CI 0.16 1.13), and 65% at 6 months (Peto OR = 0.35; 95% CI 0. 16 0.75) following vaccination. REVIEWER'S CONCLUSIONS: Vaccination, in the autumn, of patients with recurrent exacerbations of bronchitis reduced the number and severity of exacerbations over the winter months. A large clinical trial to assess longer term prognosis needs to be completed.

Acute Disease↗
PubMed2005

Pain exacerbation as a major source of lost productive time in US workers with arthritis.

OBJECTIVE: To estimate the prevalence of arthritis and arthritis pain exacerbations in US workers including impact on functioning and lost productive work time (LPT). METHODS: The research was conducted as a nested case-control study of participants in the Caremark American Productivity Audit, a US national random-digit-dial survey of US workers. The sample included 329 workers ages 40-65 years meeting the First National Health and Nutrition Examination Survey criteria for arthritis, and 91 workers not meeting arthritis inclusion criteria. Participants completed a telephone interview to measure the prevalence of arthritis and pain exacerbations, LPT (in hours and dollars), functional disability using the Western Ontario and McMaster Universities Knee and Hip Osteoarthritis Index (WOMAC) and the Australian/Canadian Osteoarthritis Hand Index, and demographics. RESULTS: The prevalence of arthritis in US workers ages 40-65 years was 14.7% during the 2-week period. Pain exacerbation occurred among 38% of participants with arthritis. Workers with pain exacerbations were significantly more likely to have higher WOMAC scores (38.6 versus 29.6; P = 0.0041) and report arthritis-related LPT (24.4% versus 13.3%; P = 0.0118) than workers without exacerbations. Among those with LPT, average LPT did not differ (4.1 hours per week) between persons with and without exacerbations. The estimated annual LPT cost from arthritis in the US workforce was $7.11 billion, with 65.7% of this cost attributed to the 38% of workers with pain exacerbations. CONCLUSION: Workers with arthritis pain exacerbation account for a disproportionate share of the arthritis-related LPT cost. Stratifying workers for appropriate treatment management based on pain exacerbation status could significantly decrease arthritis-related LPT and offer employees and employers an effective return on health care use.

Absenteeism↗
PubMed2006

Exacerbations, hospital admissions and impaired health status in chronic obstructive pulmonary disease.

Impaired health status may be a risk factor for frequent exacerbations and hospital admission and, in turn, exacerbations and admissions may further impair the health status of patients with COPD. We have investigated the variables associated with frequent exacerbations (3 or more per year) and admission, with particular interest in health status, in a cohort of ambulatory patients with moderate to severe COPD attended by chest physicians in Spain. A total of 227 investigators included 1057 patients with a mean predicted FEV1 of 41.8%. The mean total score on the St. George's Respiratory Questionnaire (SGRQ) was 47.9 units, and 300 patients (28.4%) had 3 or more exacerbations the previous year and 344 (32.6%) were admitted at least once during the same period. In multivariate analysis only the SGRQ total score was significantly associated with both frequent exacerbations (OR = 1.04; 95% CI = 1.01-2.12; p<0.0001) and admission (OR = 1.01; 95% CI = 1.00-1.02; p = 0.0008). Other variables significantly associated with frequent exacerbations were chronic mucus hypersecretion, increased baseline dyspnea, comorbidity, GOLD stage IV and treatment with inhaled corticosteroids. Variables associated with admission were lower educational level, increased number of exacerbations, use of long-term oxygen therapy and use of short acting beta-2 agonists. An impaired health status is associated with an increased number of exacerbations and with admission to hospital in the previous year. These results, together with previous studies, confirm that impairment in health status in COPD is both a marker of risk for, and a consequence of, frequent exacerbations and admissions.

Aged↗
PubMed2006

Exacerbations of chronic obstructive pulmonary disease--a patients' perspective.

BACKGROUND: Exacerbations are now an important clinical variable for research into, and management of, chronic obstructive pulmonary disease (COPD). Emphasis is usually on reductions in the incidence of exacerbations and their impact on quality of life. For such research to be useful and comparable there needs to be a clearly defined understanding of what is meant by the term 'exacerbation'. The aim of this study was to explore the notion of COPD exacerbations from the viewpoint of patients who had recently suffered an exacerbation. METHODS: Using principles from grounded theory we conducted semi-structured, in-depth interviews with 23 volunteers from Denmark, the Netherlands and the UK who were identified as having had a COPD exacerbation. Interviews were recorded locally and translated into English for analysis. Notable themes were identified for each informant and their occurrences compared. RESULTS: Patients' reasons for consulting fell into four categories: 'frightening change'; 'change in sputum colour'; 'gradual deterioration'; and 'opportunistic diagnosis'. Most patients consulted frequently about their COPD, but did not afford their exacerbations the same degree of prominence as healthcare professionals (HCPs). CONCLUSIONS: These data provide a new way of thinking about COPD exacerbations, offering a greater understanding and classification of the reasons underlying the decision of COPD patients to consult with HCPs. They suggest that the patient perspective of exacerbations is more complex than previously thought. These findings could be applied to clinical practice and research, facilitating focussed decisions on COPD management.

Acute Disease↗
PubMed2006

Economic aspects of antimicrobial therapy of acute exacerbations of COPD.

This article synthesizes and appraises the methodological quality of the international literature on costs of chronic obstructive pulmonary disease (COPD) exacerbations, economic value of antimicrobial therapy of exacerbations, and factors affecting the economic value of antibiotics. Included studies had carried out a cost-of-illness, cost-effectiveness, cost-utility or cost-benefit analysis. Exacerbation costs varied between countries and increased with the severity of the exacerbation. Hospitalization costs accounted for more than 45% of healthcare costs of exacerbations. Drug costs made up 6-21% of healthcare costs in the majority of studies. Cost estimates were biased due to difficulties involved in diagnosing and treating exacerbations, and because the patient sample studied may not be representative of the population of patients suffering from exacerbations. Although this needs to be corroborated by future research, evidence is emerging that second-generation antibiotics such as fluoroquinolones may have a favourable economic profile as compared with first-generation antibiotics. The higher acquisition costs of fluoroquinolones appear to be balanced by less treatment failure, more time between exacerbation episodes, and lower hospitalization costs. There is a need for prospective economic evaluations alongside clinical trials with a sufficient number of patients and length of follow-up period. The economic value of antibiotics is influenced by difficulties involved in diagnosing the condition, effectiveness, resistance, patient compliance with treatment, and treatment failure associated with antibiotics. The small number of economic evaluations and their methodological limitations precludes the recommendation of a specific antibiotic for use in the management of COPD exacerbations on economic grounds.

Acute Disease↗
PubMed1998

Exacerbation of myasthenia gravis during the menstrual period.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder mediated by antiacetylcholine receptor antibodies. It has long been suspected to exacerbate during the menstrual period but this has never been adequately documented. SUBJECTS AND METHODS: We questioned 120 female myasthenic patients of different ages, about their myasthenic symptoms before and during the menstrual period. We also evaluated the effect of medications, pain and stress during or before the menstrual period on the exacerbation rate. Exclusion criteria were postmenopausal age and incomplete information available in the questionnaire. RESULTS: Forty two premenopausal women with generalized disease were included in the study. Twenty eight (67%) of the patients reported exacerbation of their myasthenic symptoms 2 to 3 days prior to the menstrual period. This exacerbation persisted in 22 of them to the third day of the menstrual period. In nine of the women this clinical worsening necessitated an increased intake of medications during the days prior to menstruation. No correlation could be found between the presence of antiacetylcholine receptor antibodies, pain, stress, use of oral contraceptives or the type of antimyasthenic therapy and the rate of exacerbation before and during the menstrual period. CONCLUSIONS: (1) MG frequently exacerbates before and during the menstrual period in 67% of MG patients. (2) The rate of exacerbation is unrelated to the presence of stress or pain prior to or during the menstrual period. (3) Different therapies directed against MG, as well as oral contraceptives do not influence the clinical course. (4) Menstrual exacerbations occur in both seronegative and seropositive patients. (5) These exacerbations may frequently necessitate therapeutic changes.

Adult↗