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PubMed2005

Relationship between respiratory symptoms and medical treatment in exacerbations of COPD.

Exacerbations of chronic obstructive pulmonary disease (COPD) can be defined symptomatically or by healthcare contacts, yet the relationship between these events is unknown. Data were collected during a 1-yr study of the budesonide/formoterol combination in COPD patients, where exacerbations, defined by increases in treatment, were compared with daily records of respiratory symptoms, rescue medication use and peak expiratory flow (PEF). The relationship between changes in these variables and the medical event was examined using different modelling approaches. Data from the first exacerbation treated with oral corticosteroids and/or antibiotics and/or hospitalisation (event based) were available in 468 patients. Patients exacerbating were significantly more breathless and more likely to report cough than healthy patients, but did not differ in baseline spirometry. Exacerbations defined by changes in individual symptoms were only weakly related to event-based exacerbations; however, defined with 63% of such events being predicted from symptom changes. Changes in rescue medication use or PEF were poor predictors of event-based exacerbations. The mean peak change in symptoms was closely related to the onset of therapy. In conclusion, event-based exacerbations are a valid way of identifying acute symptom change in a chronic obstructive pulmonary disease population. However, daily symptom monitoring is too variable using the current diary cards to make individual management decisions.

Acute Disease↗
PubMed2004

Managing patients with recurrent acute exacerbations of chronic bronchitis: a common clinical problem.

Chronic obstructive pulmonary disease (COPD) affects 15 million people and is the fourth leading cause of death in the United States. It places a considerable burden on the healthcare system, with exacerbations contributing to a significant proportion of this burden. Patients with recurrent exacerbation, who experience more than 2 exacerbations per year, are especially difficult to manage. Several potential host, pathogen, and treatment factors can be identified that contribute to recurrent exacerbation. Patients with recurrent exacerbations are often exposed to frequent courses of antimicrobials. Therefore, antimicrobial resistance among common bacterial pathogens is likely to be prevalent in this group of patients, and further complicates therapy in this already difficult-to-treat patient population. In the management of patients with recurrent exacerbation, one goal should be to decrease the frequency of exacerbations, for which several strategies are suggested. In this article, we will review available literature identified through an extensive search of Medline and PubMed on the characteristics and approach to management of these difficult-to-treat patients. There is a substantial need for more research to understand the etiology and identify efficacious interventions to reduce the frequency of exacerbations of COPD.

Acute Disease↗
PubMed2004

Prospective longitudinal study of children with tic disorders and/or obsessive-compulsive disorder: relationship of symptom exacerbations to newly acquired streptococcal infections.

BACKGROUND: It has been proposed that infection by group A beta-hemolytic streptococci (GABHS) can trigger acute symptom exacerbations among patients with Tourette's syndrome (TS) or obsessive-compulsive disorder (OCD), via autoimmune mechanisms. OBJECTIVE: To examine the temporal relationship between newly acquired GABHS infections (and other immunologic indices) and acute exacerbations of tics and obsessive-compulsive symptoms. METHODS: Pediatric patients (7-17 years of age) with TS and/or OCD (N = 47) and healthy control subjects (N = 19) were prospectively monitored for newly acquired GABHS infections, nonspecific markers of acute inflammatory responses, and D8/17-reactive cells (a marker of rheumatic fever). Objective monthly ratings of tic and obsessive-compulsive symptom severity were used to determine the timing of symptom exacerbations. RESULTS: The overall rate of acute exacerbations of neuropsychiatric symptoms was 0.56 exacerbations per patient per year. The average rate of new GABHS infections, using a stringent definition, was 0.42 infections per subject per year among patients, compared with 0.28 infections per subject per year for control subjects. The association between symptom exacerbations and new GABHS infections among patients was no greater than that expected on the basis of chance. At baseline, patients demonstrated significantly higher levels of D8/17-reactive cells and neopterin, compared with control subjects, but there was no consistent pattern of change when exacerbation time points were compared with baseline or follow-up time points. CONCLUSIONS: The results suggest no clear relationship between new GABHS infections and symptom exacerbations in an unselected group of patients with TS and/or OCD.

Acute Disease↗
PubMed1994

Radiographic changes in acute exacerbations of cystic fibrosis in adults: a pilot study.

OBJECTIVE: We set out to determine whether specific findings can be seen on chest radiographs of adult patients with cystic fibrosis who are having acute exacerbation of respiratory disease. MATERIALS AND METHODS: Over a 2-year period, 22 adults with cystic fibrosis had both a baseline chest radiograph and a radiograph obtained either because of acute exacerbation or for some other reason (nonexacerbation). Fourteen radiographic features, including mucous plugs, air-space disease, peribronchial thickening, bronchiectasis, fluid levels, and lymphadenopathy, were scored retrospectively by two radiologists, who did not have knowledge of the patient's clinical condition, as being present, absent, increased, decreased, or unchanged. An overall assessment (better, worse, or no change) was also given for each radiograph. Data were analyzed in two ways (per individual episode and per individual patient) by using contingency tables, with statistical significance determined by exact permutation testing. RESULTS: Of the 22 patients, 13 had 29 exacerbations and eight had 11 nonexacerbations. The remaining patient had radiographs showing both an exacerbation and a nonexacerbation. With the exception of overall change (p = .06), none of the radiographic variables showed a statistically significant association with exacerbation (mean p value, .66; range, .19-.90). CONCLUSION: The 14 specific radiographic findings studied, including peribronchial thickening, mucous plugs, air-space disease, and fluid levels, were not useful in determining whether an adult patient with cystic fibrosis was having acute exacerbation of the disease. With regard to these individual variables, chest radiographs are not helpful in the management of acute exacerbation of cystic fibrosis in adults. However, overall change approached statistical significance (p = .06). The value of chest radiography lies more in excluding the rare major complication, such as pneumothorax, than in diagnosing the usual exacerbation.

Acute Disease↗
PubMed2006

Exacerbations and associated healthcare cost in patients with COPD in general practice.

BACKGROUND: Acute exacerbations are a characteristic clinical expression of chronic obstructive pulmonary disease (COPD). The objective of this study was to investigate the occurrence rate, management, and healthcare costs of exacerbations in patients with COPD in Dutch general practice. METHODS: Baseline data set from the COPD on Primary Care Treatment (COOPT) trial was used. Details on the occurrence and management of exacerbations were collected by systematic medical record review for the 2-year period preceding trial inclusion. RESULTS: The mean age of the 286 study subjects involved was 59.2 (SD 9.6) years, postbronchodilator FEV1 67.1% (SD 16.2) of predicted. Following ERS criteria, subjects suffered from: no (26%); mild (19%); moderate (40%); or severe (15%) airflow obstruction. The overall mean and median annual exacerbation rates were 0.88 (SD 0.79) and 0.5 (IQR 1.0), respectively. Exacerbation rate was not related to severity of airflow obstruction (p=0.628). Mean annual exacerbation costs per subject were 40 Euro, 53 Euro, 61 Euro and 92 Euro for the respective severity subgroups (p=0.012). The increase of costs in the more severe subgroups was mainly attributable to more physician consultations, diagnostic procedures, and prescription of reliever medication (e.g., bronchodilators, cough preparations). CONCLUSIONS: Occurrence of exacerbations did not depend on the severity of airflow obstruction, whereas the healthcare cost associated with exacerbations increased along with the severity of the disease.

Aged↗
PubMed2002

A single high dose of inhaled corticosteroids: a possible treatment of asthma exacerbations.

UNLABELLED: Recovery from an asthma exacerbation may take days or weeks even after the introduction of appropriate exacerbation therapy. However airway responsiveness and sputum eosinophils can be reduced within 6 hours by a single dose of inhaled corticosteroids. AIM: To determine if a single dose of 3200 microg of budesonide increases the rate of recovery from an asthma exacerbation. METHODS: Nineteen asthmatic subjects with an asthma exacerbation following withdrawal of inhaled corticosteroids were randomised to receive either usual care (doubling their dose of inhaled corticosteroids) plus placebo or usual care plus a single dose of 3200 microg of budesonide in a double-blind manner. Subjects monitored peak flow (PEF), symptoms, and beta agonist use daily for four weeks. The lowest PEF reading for each week was calculated as a percentage of the best peak flow value achieved in the recent past (PEF lowest % best). RESULTS: In the first week following exacerbation, PEF (lowest % best) was significantly greater in the budesonide group than in the placebo group (87.4 +/- 4.7 vs. 76.7 +/- 5.3; p = 0.029). However in the fourth week following exacerbation PEF was not significantly different (p = 0.728). The proportion of subjects who had a symptom free day during the first week was significantly higher in the budesonide group (p = 0.0012). CONCLUSION: A single high dose of inhaled corticosteroids added to usual exacerbation treatment might increase the rate of recovery from a mild exacerbation of asthma.

Administration, Inhalation↗
PubMed2000

Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels.

BACKGROUND: Respiratory tract infections may acutely increase risk from coronary heart disease (CHD), though the mechanisms have not been defined. Patients with chronic obstructive pulmonary disease (COPD) are prone to repeated exacerbations that are often associated with respiratory infections. These patients also have increased cardiovascular morbidity and mortality. We hypothesized that transient acute increases in plasma fibrinogen, an independent risk factor for CHD, could occur at COPD exacerbation (mediated through a rise in IL6) and thereby provide a mechanism linking respiratory infection to risk of coronary heart disease. METHODS: 93 COPD patients [mean (SD) age 66.8 (8.1) years] were followed regularly over one year, with daily diary card monitoring of respiratory symptoms and peak expiratory flow rate (PEFR); 67 patients [mean FEV1 1.06 (0.44) l, FVC 2.43 (0.79) l] were seen during 120 exacerbations. At each visit spirometry was measured and blood samples taken for plasma fibrinogen and Interleukin-6 (IL-6) levels. RESULT: At baseline, the mean (SD) plasma fibrinogen was elevated at 3.9 (0.67) g/l in the 67 patients with exacerbations during the study and the median (IQR) IL-6 at 4.3 (2.4 to 6.8) pg/ml. Plasma fibrinogen increased by 0.36 (0.74) g/l at exacerbation (p <0.001). with IL-6 levels rising by 1.10 (-2.73 to 6.95) pg/ml (p = 0.008). There was a relation between the changes in fibrinogen at exacerbation and IL-6 levels (r = 0.348, p <0.001). Multiple regression revealed significantly greater rises in fibrinogen when exacerbations were associated with purulent sputum (b = 0.34 g/l; p = 0.03), increased cough (b = 0.31 g/l, p = 0.019) and symptomatic colds (b = 0.228; p = 0.024). CONCLUSIONS: Plasma fibrinogen levels were elevated in stable patients with COPD and may contribute to the increased cardiovascular morbidity and mortality in these patients. COPD exacerbations increased serum IL-6 levels, leading to a rise in plasma fibrinogen. Thus acute rather than chronic infection may have a role in predisposing to coronary heart disease or stroke.

Aged↗
PubMed2006

[The changes and clinical implications of serum procalcitonin in acute exacerbations of chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the changes and clinical implications of serum procalcitonin (PCT) in acute exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: A total of 45 patients with an acute exacerbation of COPD were studied. On presentation, serum PCT concentrations were measured, and quantitative sputum culture was also performed. The patients were reevaluated when they had returned to their stable clinical state. Potentially pathogenic microorganism (PPM) was only regarded as significant if they reached a growth of >or= 10(7) CFU/ml, indicating the presence of bacterial exacerbation of COPD. RESULTS: (1) On presentation, sputum samples from 21 (46.7%) patients yielded PPM. When reevaluated in stable clinical state, sputum samples from 9 (20%) patients had a positive PPM culture [2.8 x 10(6) (1.3 x 10(6), 1.9 x 10(7)) CFU/ml], but with a significantly lower bacterial load than on presentation [7.0 x 10(7) (4.5 x 10(7), 7.1 x 10(8)) CFU/ml, Z = -2.666, P = 0.008]. (2) The patients were classified into two groups: group A included patients with bacterial exacerbation of COPD (n = 15), group B included patients with nonbacterial exacerbation of COPD (n = 30). The levels of PCT for patients of group A [0.24 (0.17, 0.28) microg/L] were significantly higher than group B [0.13 (0.10, 0.18) microg/L, Z = -3.531, P = 0.000]. When they had returned to their stable state, the levels of PCT for patients of group A decreased to 0.12 (0.10, 0.14) microg/L, which was significantly lower than in exacerbation [0.24 (0.17, 0.28) microg/L, Z = -3.298, P = 0.001]; But compared with exacerbation [0.13 (0.10, 0.18) microg/L], the levels of PCT for patients of group B did not changed [0.13 (0.10, 0.15) microg/L, Z = -1.614, P = 0.107]. In the stable state, there were no differences in the PCT measurement between the two groups (Z = -0.382, P = 0.703). CONCLUSION: In patients presented with an acute exacerbation of COPD, the elevation of serum PCT is associated with bacterial infection.

Aged↗
PubMed1991

Changes in levels of antibodies against the 70 kDa and a polypeptides of the U1RNP complex in relation to exacerbations of systemic lupus erythematosus.

In order to investigate whether disease exacerbations of systemic lupus erythematosus (SLE) are accompanied or preceded by changes in antibody levels against the U1RNA associated 70 kDa and A polypeptides, we prospectively collected plasma specimens from 71 patients with SLE. We compared changes in anti-70 kDa/anti-A levels, measured by ELISA using cloned antigens, with changes in levels of anti-dsDNA and total IgG. Measurable levels of anti-70 kDa (n = 10) and/or anti-A antibodies (n = 6) were detected during 10 exacerbations. Four of the 10 exacerbations with a measurable level of anti-70 kDa antibodies were preceded by a significant rise in anti-70 kDa levels, 2 by a significant fall, while levels of anti-70 kDa did not change in the remaining 4 cases. Only one of the 6 exacerbations with detectable anti-A antibody levels was preceded by a significant rise in anti-A antibodies, while levels did not change before exacerbation in the other 5 cases. Six of the 10 exacerbations were preceded by a significant rise in anti-dsDNA; in 4 cases levels of anti-dsDNA did not change before exacerbation. In contrast to anti-dsDNA, no relation was found between changes in levels of anti-70 kDa/anti-A and changes in disease activity. Significant changes in levels of anti-70 kDa/anti-A, occurring in 6 cases, were accompanied by parallel changes in total IgG in 5 of these 6. We conclude that, in contrast to anti-dsDNA, serial measurement of levels of anti-70 kDa/anti-A is not useful for monitoring disease activity or predicting disease exacerbations in SLE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Risk of multiple sclerosis exacerbation during pregnancy and breast-feeding.

Studies in the past have reported an increased risk of exacerbations in multiple sclerosis during the postpartum period; it is not known whether breast-feeding alters this risk. We interviewed 435 women regarding pregnancy and breast-feeding history, providing for analysis 191 pregnancies that had occurred during a nonprogressive phase of the disease. The exacerbation rates during the nine-month postpartum period (34%) were more than three times the exacerbation rate during the nine months of pregnancy (10%). The exacerbation risk was highest in the three-month period following childbirth and appeared to stabilize after the sixth postpartum month. The exacerbation rates in breast-feeding and non-breast-feeding pregnancies were 38% and 31%, respectively. The average time to exacerbation was similar in breast-feeding (3.0 months) and non-breast-feeding (3.1 months) pregnancies. Although differential exacerbation rates during pregnancy and the postpartum period may be related to hormonal effects on the immune system, the hormonal effects of breast-feeding do not appear to similarly affect the risk of exacerbation.

Adolescent↗
PubMed1993

Pro: antibiotics for chronic bronchitis with exacerbations.

Over the years, there has emerged a considerable body of evidence supporting the importance of antimicrobial therapy in exacerbations of chronic bronchitis. The following lines of evidence suggest that most acute exacerbations are caused by bacterial infection: (1) the individual with chronic bronchitis is susceptible to bacterial infection as a consequence of local damage from prolonged cigarette smoking; (2) subtle defects in the local immune system can be shown, including impaired particle transport, defective immunoglobulin A production, chronic mucous impaction, and defective neutrophil phagocytosis; (3) acute bronchitic exacerbations are associated with a proliferation of pathogenic bacteria in the lower respiratory tract, based on quantitative culture data obtained by bronchoscopy with a protected specimen brush; (4) viral respiratory infections, which were once linked to over 50% of purulent exacerbations, probably account for only a minority of bronchitic exacerbations; (5) some "culture negative" exacerbations may be caused by bacteria susceptible to antibiotics such as Mycoplasma pneumoniae or Chlamydia pneumoniae. There are also secondary effects of bacteria that are potentially amenable to antibiotic therapy. Bacteria that colonize the respiratory tract of chronic bronchitics cause direct damage to the respiratory epithelium. Lipooligosaccharide, a major component of the outer membrane of Haemophilus influenzae, is an endotoxin-like mediator of respiratory cell damage. The host inflammatory response to bacterial proliferation is ineffective and may be potentially harmful; the enzyme neutrophil elastase is released by the host during phagocytosis of bacteria and may lead to progressive airway damage. In addition, bacterial superinfections may complicate viral exacerbations of chronic bronchitis. Clinical trials examining the efficacy of antibiotic therapy in mild to moderate exacerbations of chronic bronchitis have yielded conflicting results, caused in part to fundamental differences in study design. The major double-blinded and placebo-controlled studies suggest a trend in favor of antimicrobial therapy, although the effect is modest. For the individual patient, the risks of antimicrobial therapy are small compared with the potential benefits of returning to work earlier and avoiding the rare case of respiratory decompensation.

Anti-Bacterial Agents↗
PubMed2003

In-hospital mortality following acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a frequent cause of hospitalization in the United States. Previous studies of selected populations of patients with COPD have estimated in-hospital mortality to range from 4% to 30%. Our objective was to obtain a generalizable estimate of in-hospital mortality from acute exacerbation of COPD in the United States and to identify predictors of in-hospital mortality using administrative data. METHODS: We performed a cross-sectional study utilizing the 1996 Nationwide Inpatient Sample, a data set of all hospitalizations from a 20% sample of nonfederal US hospitals. The study population included 71 130 patients aged 40 years or older with an acute exacerbation of COPD at hospital discharge. The primary outcome assessed was in-hospital mortality. RESULTS: In-hospital mortality for patients with an acute exacerbation of COPD was 2.5%. Multivariable analyses identified older age, male sex, higher income, nonroutine admission sources, and more comorbid conditions as independent risk factors for in-hospital mortality. CONCLUSIONS: Mortality during hospitalization in this nationwide sample of patients with acute exacerbations of COPD was lower than that of previous studies of select populations. This estimate should provide optimism to both clinicians and patients regarding prognoses from COPD exacerbations requiring hospitalization. Our results indicate that the use of administrative data can help to identify subsets of patients with acute exacerbations of COPD that are at higher risk of in-hospital mortality.

Acute Disease↗
PubMed2005

Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease.

BACKGROUND: The culture of bronchial secretions from the lower airway has been reported to be positive for potentially pathogenic microorganisms (PPMs) in patients with stable chronic obstructive pulmonary disease (COPD), but the determinants and effects of this bacterial load in the airway are not established. METHODS: To determine the bronchial microbial pattern in COPD and its relationship with exacerbation, we pooled analysis of crude data from studies that used protected specimen brush sampling, with age, sex, smoking, lung function, and microbiologic features of the lower airway as independent variables and exacerbation as the outcome, using logistic regression modeling. RESULTS: Of 337 study participants, 70 were healthy, 181 had stable COPD, and 86 had exacerbated COPD. Differences in the microbial characteristics in the participating laboratories were not statistically significant. A cutoff point of 10(2) colony-forming units (CFU) per milliliter or greater for the identification of abnormal positive culture results for PPMs was defined using the 95th percentile in the pooled analysis of healthy individuals. Bronchial colonization of 10(2) CFU/mL or greater by PPMs was found in 53 patients with stable COPD (29%) and in 46 patients with exacerbated COPD (54%) (P<.001, chi(2) test), with a predominance of Haemophilus influenzae and Pseudomonas aeruginosa. Higher microbial loads were associated with exacerbation and showed a statistically significant dose-response relationship after adjustment for covariates (odds ratio, 3.62; 95% confidence interval, 1.47-8.90), but P aeruginosa persisted as a statistically significant risk factor after adjustment for microbial load (odds ratio, 11.12; 95% confidence interval, 1.17-105.82). CONCLUSIONS: One quarter of the patients with COPD are colonized by PPMs during their stable periods. Exacerbation is associated with the overgrowth of PPMs and with the appearance of P aeruginosa in the lower airway, which is associated with exacerbation symptoms independent of load.

Aged↗
PubMed1989

Elevated levels of 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum during acute exacerbation of chronic hepatitis B.

We measured 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum of 14 HBsAg- and HBeAg-positive patients with chronic hepatitis B with or without acute exacerbation. Elevated levels of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells and serum were found in seven chronic hepatitis B patients with acute exacerbation, whereas in the remaining seven chronic hepatitis B patients without acute exacerbation, both levels were similar to those of normal subjects despite active hepatitis B virus multiplication. 2',5'-Oligoadenylate synthetase levels in peripheral blood mononuclear cells and serum, which were not statistically different from those of normal subjects prior to acute exacerbation, increased during acute exacerbation from 3- to 23-fold over initial levels following elevations in ALT activity. 2',5'-Oligoadenylate synthetase levels fluctuated over a normal range while ALT levels were elevated, and they returned to a baseline with ALT normalization. This suggests that the in vivo interferon system may be activated during acute exacerbation, and that this activation may not be a result of hepatitis B virus multiplication alone, but also of a host-immune response to hepatitis B virus multiplication. Three patients were treated with interferon during acute exacerbation. All three had elevated levels of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells and serum just before treatment. 2',5'-Oligoadenylate synthetase levels increased only 1.1- to 2.2-fold over initial levels during treatment, with none of the patients clearing HBeAg during and after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed2005

High replicative full-length lamivudine-resistant hepatitis B virus isolated during acute exacerbations.

During chronic HBV infections, exacerbations of disease usually occur without clearly understood mechanisms. In this study, full-length HBV genomes were analyzed from four chronic hepatitis B patients who developed resistance to lamivudine [-2'-deoxy-3'-thiacytidine, LMV] accompanied by acute exacerbation of disease. Paired full-length HBV isolates were cloned from the sera of patients prior to LMV treatment and after drug resistant breakthrough isolates emerged with exacerbation. Compared to the isolates before treatment, isolates from all four patients during exacerbation showed marked increase in replicative competence by cell transfection study. Viral genome amplification and direct sequencing was used further to study the sequence differences between the dominant species and the clones used for functional analysis. Apart from mutations at the YMDD motif, no shared mutations were shown between all isolates. The isolates from the one patient who recovered from the exacerbation showed a lower number of mutations, and in particular, lacked basal core promoter (BCP) mutations at 1762/1764. In contrast, BCP mutations were found in isolates from the other three patients. Thus, in patients with acute exacerbation, high replicative strains might be selected from the total HBV quasispecies during treatment, and amongst these strains, those with core promoter mutations were most likely to be associated with severe clinical exacerbations.

Amino Acid Substitution↗
PubMed2003

Effect of long-acting beta2 agonists on exacerbation rates of asthma in children.

The purpose of this analysis was to examine the effect of long-acting beta(2)-adrenoceptor agonists (LABAs) on the asthma exacerbation rate in pediatric patients. Randomized controlled trials (RCT) that included the use of LABAs to treat symptoms of pediatric asthma in children on inhaled corticosteroids, that reported asthma exacerbation rates, and that were published as full papers in peer-reviewed journals were retrieved from a search of the medical literature. Eight studies were identified that fulfilled these criteria. An exacerbation was defined as deterioration in a patient's asthma requiring a change in prescribed medication or not defined but reported as an asthma exacerbation or an asthma-related hospitalization. Analysis of data from the eight studies revealed no apparent protection from an asthma exacerbation among children on a LABA compared to patients on comparator treatment. The relative risk of an asthma exacerbation for LABA compared to placebo or short-acting beta(2)-adrenoceptor agonist (SABA) ranged from 0.95-1.86. The relative risk of hospitalization for asthma in patients treated with LABAs with regular maintenance with ICS ranged from 3.3-21.6 in the three studies that reported asthma-related hospitalizations. The lack of evidence for the control of asthma exacerbations in children regularly using a LABA should bring into question its general use as add-on therapy. Studies should be designed to directly explore the implications of these observations in pediatric patients.

Administration, Inhalation↗
PubMed2003

Preventing exacerbations of chronic bronchitis and COPD: therapeutic potential of mucolytic agents.

It is important to find interventions that will reduce the frequency and severity of exacerbations of COPD, because of their effect on morbidity and healthcare expenditure. A Cochrane systematic review included 23 studies that had evaluated the effects of treatment with mucolytic agents in patients with chronic bronchitis or COPD. Mucolytic treatment was associated with a significant reduction of 0.79 exacerbations per patient per year compared with placebo, a 29% decrease. Patients who received treatment with mucolytic agents were twice as likely to remain exacerbation-free in the study period than if they had received placebo, with six patients needing regular treatment with mucolytic agents for 3-6 months to achieve one less exacerbation over that time. Treatment with mucolytic agents resulted in nearly 7 days less illness per patient per year. How mucolytic agents work is unknown, although they may reduce exacerbations by altering mucus production, antioxidation, or antibacterial or immunostimulatory effects. They do not appear to affect the decline in lung function that occurs in COPD. The treatment appears to be without any adverse effects, apart from the need to take oral medication daily. Cost-effectiveness analysis suggests that the point at which the costs of treatment and non-treatment were equal was 1.2 less exacerbations per year. This is higher than the effect observed in the Cochrane review, suggesting that treating everyone with COPD with mucolytic agents would not be cost effective. Those with more frequent and severe exacerbations appear to have the most to gain.

Bronchitis, Chronic↗
PubMed2005

The quality of life impact of acute exacerbations of chronic bronchitis (AECB): a literature review.

BACKGROUND: The impact of acute exacerbations of chronic bronchitis (AECB), a common consequence of chronic obstructive pulmonary disease (COPD), is extensive, with symptoms ranging from mild to life threatening. Health-related quality of life (HRQL) is impaired in patients with COPD, but little is known about the direct effect of exacerbations on HRQL. METHODS: MEDLINE and EMBASE literature searches were conducted; reference lists of identified articles were reviewed. RESULTS: Eighteen studies reporting the impact on HRQL of acute exacerbations were identified. Study design and patient population varied. Six studies evaluated HRQL once; only four studies used both generic and disease-specific HRQL measures. Cross-sectional studies reported HRQL decrements during exacerbations and suggested that HRQL is a good predictor of health care resource utilization. Pharmacological treatment led to within-group improvements following AECBs. Non-pharmacological intervention studies were small and inconclusive. Longitudinal studies, assessing pharmacological and non-pharmacological interventions, found that HRQL improved from exacerbation to recovery, with responsiveness depending on sensitivity of the measure. Frequency of exacerbations was a significant predictor of HRQL. CONCLUSIONS: Exacerbations lead to substantial reductions in HRQL, both in physical as well as other domains. Further research should assess the impact of specific treatment regimens and the timeline for the recovery process.

Bronchitis↗