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PubMed2003

Longitudinal changes in the nature, severity and frequency of COPD exacerbations.

Exacerbations are an important feature and outcome measure in chronic obstructive pulmonary disease (COPD), but little is known about changes in their severity, recovery, symptom composition or frequency over time. In this study 132 patients (91 male; median age 68.4 yrs and median forced expiratory volume in one second (FEV1) 38.4% predicted) recorded daily symptoms and morning peak expiratory flow. Patients were monitored for a median of 918 days and 1,111 exacerbations were identified. Patients with severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) category III, n=38) had an annual exacerbation frequency of 3.43 x yr(-1), 0.75 x yr(-1) higher than those with moderate COPD (GOLD II, n=94). Exacerbation frequency did not change significantly during the study. At exacerbation onset, symptom count increased to 2.23, relative to a baseline of 0.36 set 8-14 days previously, and this increase rose by 0.05 x yr(-1). Recovery to baseline levels in symptoms and FEV1 took longer (0.32 and 0.55 days x yr(-1)). Sputum purulence at exacerbation became more prevalent over time by 4.1% x yr(-1) from an initial value of 17%. The results of this study suggest that over time, individual patients have more symptoms during exacerbations, with an increased chance of sputum purulence and longer recovery times.

Aged↗
PubMed2004

Inhaled corticosteroids and the risk of a first exacerbation in COPD patients.

The role of inhaled corticosteroids (ICS) in asthma is well established, but their benefit in the management of chronic obstructive pulmonary disease (COPD) is still controversial. The current study assessed whether ICS are effective in preventing a first exacerbation of COPD. A cohort of newly treated COPD patients was formed from the Administrative Databases of Saskatchewan Health. The outcome was the occurrence of a first moderate or severe exacerbation from 1990-1999. Moderate exacerbations involved prescriptions for an antibiotic and an oral corticosteroid on the same day. Severe exacerbations were hospitalisations with a primary discharge diagnosis of COPD. A nested case-control design was used and matched on year of birth and cohort entry. Rate ratios (RR) were further adjusted for use of other medication and other confounders. There were 995 exacerbations among 4,455 subjects. The rate of a first exacerbation was increased with any use of ICS in the year prior to the index date (RR: 1.27; 95% CI: 1.08-1.48) and with current use (RR: 1.51; 95% CI: 1.22-1.87), and it increased with increasing daily doses of ICS. Inhaled corticosteroids do not seem to be beneficial in reducing the risk of a first exacerbation of chronic obstructive pulmonary disease.

Administration, Inhalation↗
PubMed2005

Airway inflammation during stable and acutely exacerbated chronic obstructive pulmonary disease.

The aim of this study was to clarify the mechanism of increased airway inflammation during an acute exacerbation. A total of 68 chronic obstructive pulmonary disease patients in a stable phase were enrolled and followed-up for 2-3 yrs. Inflammatory cells were analysed, and interleukin (IL)-8, neutrophil elastase, eotaxin, tryptase and RANTES (regulated on activation, normal T-cell expressed and secreted) were measured in sputum, both in a stable phase and during acute exacerbation. Out of 68 patients, 30 (unstable group) developed an acute exacerbation and expectorated adequate sputum during exacerbation. Thirty-two patients (stable group) did not develop any exacerbation for 2-3 yrs. The number of neutrophils, lymphocytes and eosinophils, and the levels of IL-8, eosinophil cationic protein (ECP), eotaxin and tryptase in sputum obtained from patients in both groups during the stable phase were significantly higher than those from healthy nonsmokers. There were no significant differences in cell analysis and biomarkers between the two groups, but patients in the unstable group showed more severe airflow limitation. In the unstable group, total cells, lymphocytes, neutrophils and eosinophils, and IL-8, neutrophil elastase, ECP and RANTES levels were significantly increased during an exacerbation from values in a stable phase. These findings suggest that exacerbation of chronic obstructive pulmonary disease may associate with additional increases in airway inflammation mediated by neutrophils, lymphocytes, eosinophils, interleukin-8 and RANTES.

Acute Disease↗
PubMed2006

The effect of tiotropium on exacerbations and airflow in patients with COPD.

This randomised, double-blind, parallel-group, 1-yr study compared the effect of tiotropium 18 microg once daily (n=500) and placebo (n=510) on exacerbations, associated health resource use (HRU) and airflow limitation in chronic obstructive pulmonary disease (COPD) patients. The mean+/-sd number of exacerbations during the past year was 2.14+/-1.40, the mean weekly morning peak expiratory flow (PEF) was 259.6+/-96.1 L.min-1 and the mean forced expiratory volume in one second (FEV1) was 1.37+/-0.45 L. Tiotropium significantly delayed the time to first exacerbation by approximately 100 days, reduced the proportion of patients experiencing more than one exacerbation by 17%, and decreased the number of exacerbations by 35% and exacerbation days by 37% versus placebo. Tiotropium also decreased HRU versus placebo, as indicated by the significant reductions in the use of concomitant respiratory medications, antibiotics and oral steroids, and the number of unscheduled physician contacts. Mean weekly morning PEF improved significantly with tiotropium versus placebo from week 1 until the end of the study. At the end of the study, tiotropium significantly improved trough (pre-dose) FEV1, forced vital capacity, slow vital capacity and inspiratory capacity versus placebo. In conclusion, tiotropium reduced exacerbations and associated health resource use, and improved airflow over 1 yr in chronic obstructive pulmonary disease patients.

Aged↗
PubMed2006

Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features.

Although acute exacerbations of idiopathic pulmonary fibrosis are well recognised, there are no studies documenting their prevalence or identifying pre-existing risk factors. This study analysed the clinical, radiological and pathological data of 11 patients who satisfied the criteria for acute exacerbation among 147 patients with biopsy-proven idiopathic pulmonary fibrosis. There were five additional patients who had similar demographics, radiology and surgical lung biopsy pathology, but had clinically less severe disease, and so were not included. The 2-yr frequency of acute exacerbation was 9.6% after the diagnosis. Most exacerbations were idiopathic, although two cases presented after surgical lung biopsy and one after bronchoalveolar lavage. No significant risk factor was found by univariate proportional hazard analysis. Imaging revealed diffuse bilateral ground-glass opacification superimposed on subpleural reticular and honeycombing densities. The biopsies of four patients taken during acute exacerbation exhibited diffuse alveolar damage superimposed upon usual interstitial pneumonia. The findings of this study demonstrate that acute exacerbation of idiopathic pulmonary fibrosis is rather common and this exacerbation is likely to have a spectrum of severity.

Acute Disease↗
PubMed1995

Asthma medications and disease exacerbations: an epidemiological study as a method for asthma surveillance.

Recent experimental and epidemiological studies have suggested that outcomes of asthma are significantly influenced by treatment patterns. This study was conducted in order to investigate the links between treatment patterns in asthmatics and occurrence of disease exacerbations. We performed a nested case-control study in a cohort of 680 asthmatics identified between 1986 and 1991 in a drug dispensing database. After validation in a pilot study, the intermittent use of oral corticosteroids was used as a proxy for asthma exacerbations. Cases with an exacerbation (n=133) were pair-wise matched with controls. The type of medications used for the usual treatment of asthma were examined in relation to the risk of asthma exacerbation. The use of oral xanthines and inhaled fenoterol but not of inhaled salbutamol, corticosteroids, cromoglycate and ipratropium bromide was associated with an increased probability of asthma exacerbation. Within the cohort, the proportion of subjects dispensed inhaled corticosteroids rose from 12 to 27% between 1986 and 1991. The proportion of subjects using inhaled bronchodilators without inhaled corticosteroids also decreased over this period of time. The identification of markers of asthma exacerbations made it possible to link the probability of adverse outcome risk for such exacerbations with treatment patterns. This method could be useful in further development of asthma surveillance using drug dispensing databases.

Adolescent↗
PubMed1997

Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease.

This study was undertaken to investigate the mechanisms that determine abnormal gas exchange during acute exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen COPD patients, hospitalized because of an exacerbation, were studied after admission and 38+/-10 (+/-SD) days after discharge, once they were clinically stable. Measurements included forced spirometry, arterial blood gas values, minute ventilation (V'E), cardiac output (Q'), oxygen consumption (V'O2), and ventilation/perfusion (V'A/Q') relationships, assessed by the inert gas technique. Exacerbations were characterized by very severe airflow obstruction (forced expiratory volume in one second (FEV1) 0.74+/-0.17 vs 0.91+/-0.19 L, during exacerbation and stable conditions, respectively; p=0.01), severe hypoxaemia (ratio between arterial oxygen tension and inspired oxygen fraction (Pa,O2/FI,O2) 32.7+/-7.7 vs 37.6+/-6.9 kPa (245+/-58 vs 282+/-52 mmHg); p=0.01) and hypercapnia (arterial carbon dioxide tension (Pa,CO2) 6.8+/-1.6 vs 5.9+/-0.8 kPa (51+/-12 vs 44+/-6 mmHg); p=0.04). V'A/Q' inequality increased during exacerbation (log SD Q', 1.10+/-0.29 vs 0.96+/-0.27; normal < or = 0.6; p=0.04) as a result of greater perfusion in poorly-ventilated alveoli. Shunt was almost negligible on both measurements. V'E remained essentially unchanged during exacerbation (10.5+/-2.2 vs 9.2+/-1.8 L x min(-1); p=0.1), whereas both Q' (6.1+/-2.4 vs 5.1+/-1.7 L x min(-1); p=0.05) and V'O2 (300+/-49 vs 248+/-59 mL x min(-1); p=0.03) increased significantly. Worsening of hypoxaemia was explained mainly by the increase both in V'A/Q' inequality and V'O2, whereas the increase in Q' partially counterbalanced the effect of greater V'O2 on mixed venous oxygen tension (PV,O2). We conclude that worsening of gas exchange during exacerbations of chronic obstructive pulmonary disease is primarily produced by increased ventilation/perfusion inequality, and that this effect is amplified by the decrease of mixed venous oxygen tension that results from greater oxygen consumption, presumably because of increased work of the respiratory muscles.

Acute Disease↗
PubMed2005

Gender differences in emergency department patients with chronic obstructive pulmonary disease exacerbation.

OBJECTIVES: Although more men are diagnosed as having chronic obstructive pulmonary disease (COPD), its prevalence is increasing among women. Little is known about gender differences in exacerbations of COPD. The objective of this study was to determine if acute presentation, management, and outcomes differ among men and women seeking care in the emergency department (ED) for exacerbation of COPD. METHODS: This was a secondary analysis of a prospective cohort study of ED patients aged 55 years or older who presented with an exacerbation of COPD. Subjects underwent structured interviews in the ED and two weeks later. RESULTS: The cohort consisted of 397 subjects with COPD, of whom 52% were women. Self-report of COPD only tended to be more common among men (61% of men vs. 52% of women), while mixed COPD/asthma tended to be more common among women (39% vs. 48%; p = 0.10). Despite reporting similar chronic symptom severity, women were less likely than men to use anticholinergic agents before their ED visit (59% vs. 69%; p = 0.04). During the exacerbation, women initiated less home therapy and were less likely to seek emergency care within the first 24 hours of symptom onset (25% vs. 36%; p = 0.01). Although ED care and disposition were similar, post-ED outcomes differed. At two-week follow-up, men were more likely to report an ongoing exacerbation (42% vs. 31%; p = 0.03). CONCLUSIONS: Men and women who present to the ED for treatment of an exacerbation of COPD have substantial differences in long-term medication use, self-treatment during exacerbation, delay in emergency care, and post-ED outcomes. Further studies are warranted to confirm and explain these gender-related differences.

Acute Disease↗
PubMed2001

Role of antimicrobial therapy in acute exacerbations of chronic obstructive pulmonary disease.

OBJECTIVE: To define the role of antimicrobial therapy in the treatment of acute bronchitic exacerbations of chronic obstructive pulmonary disease (COPD) through review of placebo-controlled clinical trials. Specificalty, to determine the benefit of antimicrobial therapy on patient outcome. DATA SOURCES: Placebo-controlled dinical trials identified by MEDLINE search (1957-December 1999). STUDY SELECTION AND DATA EXTRACTION: All placebo-controlled clinical trials that included COPD patients with no evidence of pneumonia or underlying asthma were included in the evaluation. DATA SYNTHESIS: The role of antimicrobial agents in the treatment of acute exacerbations of COPD is controversial. Patients with COPD are often chronically colonized with bacteria, and many exacerbations are due to nonbacterial causes. Four placebo-controlled clinical trials and a meta-analysis have demonstrated significant improvements in outcome for patients treated with an antibiotic versus placebo. In contrast, six studies failed to demonstrate statistical differences, possibly due to the small sample size and the subjectivity of outcome measures. Overall, the data suggest that the benefit of antimicrobial therapy in acute exacerbations of COPD may be related to exacerbation severity. CONCLUSIONS: Antimicrobial agents may have a beneficial effect in the treatment of acute exacerbations of COPD in certain patients. Pending further research in this area, we recommend antimicrobial therapy only for COPD patients with acute bronchitic exacerbations characterized by increased dyspnea, sputum volume, and purulence.

Acute Disease↗
PubMed2000

Airway inflammation and etiology of acute exacerbations of chronic bronchitis.

STUDY OBJECTIVES: The etiologic role of bacterial pathogens isolated from sputum culture in 40 to 50% of acute exacerbations of chronic bronchitis (AECB) is controversial. If bacterial pathogens cause these AECB, they should be associated with greater neutrophilic airway inflammation than pathogen-negative exacerbations. DESIGN: This hypothesis was tested by comparing levels of interleukin (IL)-8, tumor necrosis factor (TNF)-alpha, and neutrophil elastase (NE) in 81 sputum samples obtained from 45 patients with AECB. Four groups were compared. In the first three groups, nontypable Haemophilus influenzae (n = 20), Haemophilus parainfluenzae (n = 27), and Moraxella catarrhalis (n = 14) were isolated as sole pathogens, respectively. In the fourth group, only normal flora was isolated (n = 20). Paired samples, obtained from individual patients at different times, that differed in their culture results were also compared. SETTING: An outpatient research clinic at a Veterans Affairs Medical Center. PATIENTS: These patients were participating in a prospective, longitudinal study of the dynamics of bacterial infection in chronic bronchitis, for which they were seen in the study clinic on a monthly basis as well as when they were experiencing symptoms suggestive of AECB. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: H influenzae exacerbations were associated with significantly higher sputum IL-8, TNF-alpha, and NE. M catarrhalis exacerbations demonstrated significantly higher sputum TNF-alpha and NE when compared to pathogen-negative exacerbations. H parainfluenzae-associated exacerbations had an inflammatory profile similar to pathogen-negative exacerbations. Sputum elastase level distinguished bacterial from nonbacterial AECB and correlated with clinical severity of the AECB. CONCLUSIONS: Increased airway inflammation associated with isolation of H influenzae and M catarrhalis supports an etiologic role of these pathogens in AECB.

Acute Disease↗
PubMed2002

Pharmacoeconomic evaluation of acute exacerbations of chronic bronchitis and COPD.

BACKGROUND: Although exacerbations are the main cause of medical visits and hospitalizations of patients with chronic bronchitis and COPD, little information is available on the costs of their management. OBJECTIVE: This study attempted to determine the total direct costs derived from the management of exacerbations of chronic bronchitis and COPD in an ambulatory setting. METHOD: A total of 2,414 patients with exacerbated chronic bronchitis and COPD were recruited from 268 general practices located throughout Spain. Patients were followed up for 1 month. RESULTS: A total of 507 patients (21%) relapsed; of these, 161 patients (31.7%) required attention in emergency departments and 84 patients (16.5%) were admitted to the hospital. The total direct mean cost of all exacerbations was $159; patients who were hospitalized generated 58% of the total cost. Cost per failure was $477.50, and failures were responsible for an added mean cost of $100.30/exacerbation. Exacerbations of the 1,130 patients with COPD had a mean cost of $141. Sensitivity analysis showed that a 50% reduction in the failure rate (from 21 to 10.5%) would result in a total cost of exacerbation of $107 (33% reduction). CONCLUSION: Exacerbations of chronic bronchitis and COPD are costly, but the greatest part of costs derives from therapeutic failures, particularly those that end in hospitalization.

Acute Disease↗
PubMed2005

Effects of 24 weeks of lansoprazole therapy on asthma symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid reflux symptoms.

BACKGROUND: Difficult-to-control asthma has been associated with gastroesophageal acid reflux. Acid-suppressive treatment has been inconsistent in improving asthma control. OBJECTIVE: To determine whether a proton-pump inhibitor improves asthma control in adult asthmatic patients with acid reflux symptoms. DESIGN: Multicenter, double-blind, randomized, placebo-controlled trial. SETTING: Twenty-nine private practices and 3 academic practices in the United States. PATIENTS: Two hundred seven patients receiving usual asthma care including an inhaled corticosteroid (ICS). Patients had acid reflux symptoms and moderate-to-severe persistent asthma. INTERVENTION: Lansoprazole, 30 mg bid, or placebo, bid, for 24 weeks. MEASUREMENTS: The primary outcome measure was daily asthma symptoms by diary. Secondary asthma outcomes included rescue albuterol use, daily morning and evening peak expiratory flow, FEV1, FVC, asthma quality of life with standardized activities (AQLQS) questionnaire score, investigator-assessed symptoms, exacerbations, and oral corticosteroid-treated exacerbations. RESULTS: Daily asthma symptoms, albuterol use, peak expiratory flow, FEV1, FVC, and investigator-assessed asthma symptoms at 24 weeks did not improve significantly with lansoprazole treatment compared to placebo. The AQLQS emotional function domain improved at 24 weeks (p = 0.025) with lansoprazole therapy. Fewer patients receiving lansoprazole (8.1% vs 20.4%, respectively; p = 0.017) had exacerbations and oral corticosteroid-treated (ie, moderate-to-severe) exacerbations (4% vs 13.9%, respectively; p = 0.016) of asthma. A post hoc subgroup analysis revealed that fewer patients receiving one or more long-term asthma-control medications in addition to an ICS experienced exacerbations (6.5% vs 24.6%, respectively; p = 0.016) and moderate-to-severe exacerbations (2.2% vs 17.5%, respectively; p = 0.021) with lansoprazole therapy. CONCLUSION: In adult patients with moderate-to-severe persistent asthma and symptoms of acid reflux, treatment with 30 mg of lansoprazole bid for 24 weeks did not improve asthma symptoms or pulmonary function, or reduce albuterol use. However, this dose significantly reduced asthma exacerbations and improved asthma quality of life, particularly in those patients receiving more than one asthma-control medication.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Mechanisms and experimental models of chronic obstructive pulmonary disease exacerbations.

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity, mortality, and rising health care costs. In addition, they are associated with an accelerated loss of lung function and thus have a direct effect on disease progression. There are few studies examining the cellular and molecular mechanisms of COPD exacerbations. Exacerbations are linked to increased airway inflammation and oxidative stress, but many questions remain unanswered regarding the key inflammatory cells and mediators. Current therapies for COPD exacerbations are of limited effectiveness, and a better understanding of the inflammatory events at exacerbation is required to devise new therapeutic agents. The development of experimental models of exacerbation-for example, the use of experimental rhinovirus infection in humans with COPD-would greatly facilitate studies of exacerbations.

Acute Disease↗
PubMed2004

Pharmacologic interventions to reduce the risk of asthma exacerbations.

Inhaled corticosteroids (ICS) are known to reduce the risk of asthma exacerbations and asthma fatalities. In addition, an increased dose of ICS at the onset of exacerbation can reduce the need for systemic corticosteroids, although this may require a fourfold increase in dose. The overuse of short-acting beta(2)-agonists or long-acting inhaled beta(2)-agonists, used as monotherapy, increases these risks. By contrast, the use of long-acting beta(2)-agonists together with ICS has been demonstrated to reduce the doses of ICS needed for ideal asthma control, as well as to reduce asthma exacerbations. This has been best demonstrated in the Formoterol and Corticosteroids Establishing Therapy and Oxis and Pulmicort Turbuhaler in the Management of Asthma studies, which demonstrated that the combination of inhaled budesonide and formoterol reduced the risk of asthma exacerbations over that achieved by budesonide alone. Even the "as needed" use of inhaled formoterol added to ICS reduces asthma exacerbations. The combination inhaler, Symbicort, containing both budesonide and formoterol, reduced the risk of asthma exacerbations to a similar extent as the monocomponents, given separately. Treatment with either leukotriene receptor antagonists or anti-IgE also reduces the risks of asthma exacerbations, but the magnitude of the benefit compared with the combination of ICS and long-acting beta(2)-agonists is not yet known.

Administration, Inhalation↗
PubMed2003

Cyclosporin A followed by the treatment of acute exacerbation of idiopathic pulmonary fibrosis with corticosteroid.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a slowly progressive disease with a poor prognosis. Acute exacerbation is the worst stage in the clinical course of IPF, as the condition is unresponsive to most conventional therapies. Corticosteroids and other immunosuppressive drugs have been attempted for the treatment of acute exacerbation, but only with very limited effectiveness. This study was performed to examine the effect of cyclosporin A (CsA) on acute exacerbation of IPF. PATIENTS AND METHODS: Thirteen patients with acute exacerbation of IPF were retrospectively studied. All 13 patients received pulse-therapy with methylprednisolone (1,000 mg per day for 3 days), followed by oral prednisolone (40-60 mg per day). Seven patients were received CsA (1.0-2.0 mg/kg per day) after the treatment with corticosteroids. We attempted to keep the blood trough level of CsA between 100 and 150 ng/ml. RESULTS: Among the 7 patients treated with CsA, 4 patients have survived for 60, 120, 276 and 208 weeks, respectively; 2 did not respond to pulse-therapy with methylprednisolone and died within 8 weeks after the start of CsA treatment. The other patient experienced re-exacerbation and died 87 weeks after the discontinuation of CsA due to the development of viral encephalitis. In contrast, all 6 patients treated without CsA died within 66 weeks after the onset of acute exacerbation. Four of these patients responded to pulse-therapy with methylprednisolone, but their condition deteriorated again while the subsequent prednisolone was being tapered. CONCLUSION: CsA seems to prevent re-exacerbation of IPF and improve the patients' chances for long-term survival.

Acute Disease↗
PubMed2006

Temporal clinical exacerbation of summer pasture-associated recurrent airway obstruction and relationship with climate and aeroallergens in horses.

OBJECTIVE: To describe the seasonal pattern of clinical exacerbation of summer pasture-associated recurrent airway obstruction (SPA-RAO) in relation to climate and aeroallergens in horses. ANIMALS: 19 horses with SPA-RAO and 10 nonaffected horses. PROCEDURES: Daily examinations were performed on all horses while they were kept on pasture for 3 years. Onset and progression of clinical exacerbation based on a clinical score of respiratory effort were evaluated in relation to changes in maximum temperature, minimum temperature, mean temperature, maximum dew-point temperature, minimum dew-point temperature, and delta dew-point temperature. Seasonal pattern of clinical exacerbation was evaluated in relation to aeroallergen counts (20 types of fungal spores and 28 types of pollen). RESULTS: Seasonal pattern of clinical exacerbation of SPA-RAO was associated with increases in temperature (heat) and dew-point temperature (humidity), counts of fungal spores, and counts of grass pollen grains. Seasonal pattern of clinical exacerbation paralleled and was associated with increases in counts of specific types of fungal spores, particularly Basidiospore, Nigrospora, and Curvularia spp. CONCLUSIONS AND CLINICAL RELEVANCE: Although a causal relationship could not be determined, the seasonal pattern of clinical exacerbation of SPA-RAO was associated with hot and humid conditions and high environmental counts for fungal spores and grass pollen grains. It is not known yet whether these are aeroallergens that cause clinical exacerbation of the disease.

Airway Obstruction↗
PubMed2006

Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths.

BACKGROUND: Long-acting beta-agonists may increase the risk for fatal and nonfatal asthma exacerbations. PURPOSE: To assess the risk for severe, life-threatening, or fatal asthma exacerbations associated with long-acting beta-agonists. DATA SOURCES: English- and non-English-language searches of MEDLINE, EMBASE, and Cochrane databases; the U.S. Food and Drug Administration Web site; and references of selected reviews through December 2005. STUDY SELECTION: Randomized, placebo-controlled trials that lasted at least 3 months and evaluated long-acting beta-agonist use in patients with asthma. All trials allowed the use of as-needed short-acting beta-agonists. DATA EXTRACTION: Outcomes measured were Peto odds ratio (OR) and risk difference of severe exacerbations requiring hospitalization, life-threatening exacerbations requiring intubation and ventilation, and asthma-related deaths. The OR for asthma-related deaths was obtained from the Salmeterol Multi-center Asthma Research Trial (SMART). DATA SYNTHESIS: Pooled results from 19 trials with 33 826 participants found that long-acting beta-agonists increased exacerbations requiring hospitalization (OR, 2.6 [95% CI, 1.6 to 4.3]) and life-threatening exacerbations (OR, 1.8 [CI, 1.1 to 2.9]) compared with placebo. Hospitalizations were statistically significantly increased with salmeterol (OR, 1.7 [CI, 1.1 to 2.7]) and formoterol (OR, 3.2 [CI, 1.7 to 6.0]) and in children (OR, 3.9 [CI, 1.7 to 8.8]) and adults (OR, 2.0 [CI, 1.1 to 3.9]). The absolute increase in hospitalization was 0.7% (CI, 0.1% to 1.3%) over 6 months. The risk for asthma-related deaths was increased (OR, 3.5 [CI, 1.3 to 9.3]), with a pooled risk difference of 0.07% (CI, 0.01% to 0.1%). LIMITATIONS: The small number of deaths limited the reliability in assessing this risk, and 28 studies did not report information on the outcomes of interest. CONCLUSIONS: Long-acting beta-agonists have been shown to increase severe and life-threatening asthma exacerbations, as well as asthma-related deaths.

Adrenergic beta-Agonists↗
PubMed2000

[Early detection of exacerbation of lung infections in patients with cystic fibrosis by means of daily spirometry].

UNLABELLED: The clinical course of cystic fibrosis is characterised by pulmonary involvement with mucus retention, chronic pulmonary infection and parenchymal inflammation. Recurrent infectious exacerbations are usually accompanied by a fall in lung volumes. This pilot study investigated whether exacerbations can be detected early by daily spirometry. Ten patients with cystic fibrosis (5 female; 5 male; mean age 24.9 years) performed daily spirometry using a portable transtelephonic spirometer (Spirophone). Infectious exacerbations were diagnosed on clinical grounds and treated without knowledge of the spirometry results. Data of 9 patients recorded over a period of 5-11 months were analysed. One patient was excluded due to non-compliance. A total of 20 infectious exacerbations occurred during the observation period. A fall of at least 20% in one or more of the following parameters was observed in 90% (18/20) of exacerbations: FVC, FEV1, PEF, and FEF25/75. A daily drop in lung volumes of 0.7% to 1.2% was recorded beginning at a median of 33 (20 to 120) days before infectious exacerbations were diagnosed. There was a 2-3% daily improvement in spirometric data under treatment with antibiotics. CONCLUSION: Daily spirometry allows early recognition of pulmonary infectious exacerbations in patients with cystic fibrosis. Daily spirometry may be used as an indicator for early antibiotic treatment.

Adolescent↗