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PubMed2003

Exacerbations of chronic obstructive pulmonary disease.

Exacerbations of chronic obstructive pulmonary disease (COPD) cause morbidity, hospital admissions, and mortality, and strongly influence health-related quality of life. Some patients are prone to frequent exacerbations, which are associated with considerable physiologic deterioration and increased airway inflammation. About half of COPD exacerbations are caused or triggered primarily by bacterial and viral infections (colds, especially from rhinovirus), but air pollution can contribute to the beginning of an exacerbation. Type 1 exacerbations involve increased dyspnea, sputum volume, and sputum purulence; Type 2 exacerbations involve any two of the latter symptoms, and Type 3 exacerbations involve one of those symptoms combined with cough, wheeze, or symptoms of an upper respiratory tract infection. Exacerbations are more common than previously believed (2.5-3 exacerbations per year); many exacerbations are treated in the community and not associated with hospital admission. We found that about half of exacerbations were unreported by the patients, despite considerable encouragement to do so, and, instead, were only diagnosed from patients' diary cards. COPD patients are accustomed to frequent symptom changes, and this may explain their tendency to underreport exacerbations. COPD patients tend to be anxious and depressed about the disease and some might not seek treatment. At the beginning of an exacerbation physiologic changes such as decreases in peak flow and forced expiratory volume in the first second (FEV(1)) are usually small and therefore are not useful in predicting exacerbations, but larger decreases in peak flow are associated with dyspnea and the presence of symptomatic upper-respiratory viral infection. More pronounced physiologic changes during exacerbation are related to longer exacerbation recovery time. Dyspnea, common colds, sore throat, and cough increase significantly during prodrome, indicating that respiratory viruses are important exacerbation triggers. However, the prodrome is relatively short and not useful in predicting onset. As colds are associated with longer and more severe exacerbations, a COPD patient who develops a cold should be considered for early therapy. Physiologic recovery after an exacerbation is often incomplete, which decreases health-related quality of life and resistance to future exacerbations, so it is important to identify COPD patients who suffer frequent exacerbations and to convince them to take precautions to minimize the risk of colds and other exacerbation triggers. Exacerbation frequency may vary with the severity of the COPD. Exacerbation frequency may or may not increase with the severity of the COPD. As the COPD progresses, exacerbations tend to have more symptoms and take longer to recover from. Twenty-five to fifty percent of COPD patients suffer lower airway bacteria colonization, which is related to the severity of COPD and cigarette smoking and which begins a cycle of epithelial cell damage, impaired mucociliary clearance, mucus hypersecretion, increased submucosal vascular leakage, and inflammatory cell infiltration. Elevated sputum interleukin-8 levels are associated with higher bacterial load and faster FEV(1) decline; the bacteria increase airway inflammation in the stable patient, which may accelerate disease progression. A 2-week course of oral corticosteroids is as beneficial as an 8-week course, with fewer adverse effects, and might extend the time until the next exacerbation. Antibiotics have some efficacy in treating exacerbations. Exacerbation frequency increases with progressive airflow obstruction; so patients with chronic respiratory failure are particularly susceptible to exacerbation.

Adrenal Cortex Hormones↗
PubMed2004

The impact of treatment of pulmonary exacerbations on the health-related quality of life of patients with cystic fibrosis: does hospitalization make a difference?

OBJECTIVES: To investigate the impact of pulmonary exacerbations on the health-related quality of life (HRQOL) of patients with cystic fibrosis (CF) and to elucidate factors that are associated with changes in HRQOL post-exacerbation. STUDY DESIGN: Participants completed questionnaires at a pre-exacerbation visit, at the beginning of the exacerbation, and at the post-exacerbation visit. To measure HRQOL, we used the Child Health Questionnaire-Parent Form (PF-50) and the Medical Outcomes Study Short Form-36 (SF-36). We examined demographic, clinical, and treatment-related predictor variables for association with change in Physical Summary (PhS) and Psychosocial Summary (PsS) HRQOL scores after an exacerbation. RESULTS: We collected data from 48 subjects. Patients experiencing exacerbations who were treated as outpatients had a mean (SD) age of 19.5 (12.7) years and a mean pre-exacerbation forced expiratory volume in 1 second (FEV(1)) of 70% (36%) of predicted; 53% were female. Patients treated as inpatients had a mean age of 14.6 (5.5) years and a mean FEV(1) of 56% (24%); 56% were female. In univariate analyses, exacerbations were associated with a statistically significant decrease in FEV(1) (-10.0%) and PhS scores (-4.5 points). PsS scores did not significantly change with exacerbations (-0.7 points). In multivariable analyses examining change between pre-exacerbation and post-exacerbation visits, no variables were significantly associated with change in PhS scores. However, not being hospitalized for the exacerbation was associated with deterioration in PsS scores, and being hospitalized was associated with improvement in PsS scores (beta coefficient: 9.4; P <.01) by the post-exacerbation visit. Results were similar from the exacerbation to the post-exacerbation visit. CONCLUSION: In patients with CF, on average, pulmonary exacerbations affect physical HRQOL more than psychosocial HRQOL. Being hospitalized for exacerbations is associated with improvement in psychosocial HRQOL after exacerbations, whereas not being hospitalized is associated with deterioration.

Adaptation, Psychological↗
PubMed1987

Role of stress in the exacerbation of chronic illness: effects of clonidine administration on blood pressure and plasma norepinephrine, cortisol, growth hormone and prolactin concentrations.

Systolic blood pressure (SBP), diastolic blood pressure (DBP), and plasma norepinephrine (NE), cortisol (CRT), growth hormone (GH) and prolactin (PRL) were studied before and after clonidine (2.5 micrograms/kg i.m.) administration in 193 chronic severely ill patients and 193 normal subjects matched by age and sex. During exacerbation periods (positive manifestations of impairment and progressive disease), the patients showed higher NE, CRT and DBP than the normals or when they were investigated during non-exacerbation periods (92 of the 193). Clonidine induced sharp, marked reductions of NE, CRT and DBP, plus a sudden increase of GH, in all the patients during exacerbation periods. Non-significant reductions of NE, CRT and DBP were observed in normals and in patients during non-exacerbation periods. On the other hand, the GH increase registered during exacerbation periods was of an order of magnitude higher than that registered in normals and in patients during non-exacerbation periods. Significant reduction of SBP was registered both in normals and patients (exacerbation and non-exacerbation periods). Some tendency to PRL lowering was observed during exacerbation periods only. A high positive correlation between NE and DBP (pre- and post-clonidine values) was obtained during exacerbation periods in patients, but not in normals or during non-exacerbation periods in the patients. Similarly, a close negative correlation was obtained between CRT and GH (postclonidine values) during exacerbation periods, but not in normals or during non-exacerbation periods. No significant correlation was found between NE and SBP in any group of subjects. The clonidine-induced changes in GH and CRT observed in the patients during exacerbation periods were in striking contrast to the absence of these changes in depressed patients. This finding is consistent with the low rate of depression (6.7%) registered among our patients during exacerbation periods. The high plasma NE and CRT levels registered in chronic severely ill patients during exacerbation periods reflect a central and peripheral sympathetic hyperactivity, accompanied by an overactivity of the pituitary--adrenocortical axis. The strong reduction of DBP, NE and CRT, along with the sharp and great increase of GH, might be useful as indicators in assessing the exacerbation and progression of severe chronic illnesses.

Arousal↗
PubMed1998

Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease.

Exacerbations occur commonly in patients with moderate or severe chronic obstructive pulmonary disease (COPD) but factors affecting their severity and frequency or effects on quality of life are unknown. We measured daily peak expiratory flow rate (PEFR) and daily respiratory symptoms for 1 yr in 70 COPD patients (52 male, 18 female, mean age [+/- SD] 67.5 +/- 8.3 yr, FEV1 1.06 +/- 0.45 L, FVC 2.48 +/- 0.82 L, FEV1/FVC 44 +/- 15%, FEV1 reversibility 6.7 +/- 9.1%, PaO2 8.8 +/- 1.1 kPa). Quality of life was measured by the St. George's Respiratory Questionnaire (SGRQ). Exacerbations (E) were assessed at acute visit (reported exacerbation) or from diary card data each month (unreported exacerbation). In 61 (87%) patients there were 190 exacerbations (median 3; range, 1 to 8) of which 93 (51%) were reported. There were no differences in major symptoms (increase in dyspnea, sputum volume, or purulence) or physiological parameters between reported and unreported exacerbations. At exacerbation, median peak flow fell by an average of 6.6 L/min (p = 0.0003). Using the median number of exacerbations as the cutoff point, patients were classified as infrequent exacerbators (E = 0 to 2) or frequent exacerbators (E = 3 to 8). The SGRQ Total and component scores were significantly worse in the group that had frequent exacerbations: SGRQ Total score (mean difference = 14.8, p < 0.001), Symptoms (23.1, p < 0.001), Activities (12.2, p = 0.003), Impacts (13.9, p = 0.002). However there was no difference between frequent and infrequent exacerbators in the fall in peak flow at exacerbation. Factors predictive of frequent exacerbations were daily cough (p = 0.018), daily wheeze (p = 0.011), and daily cough and sputum (p = 0.009) and frequent exacerbations in the previous year (p = 0.001). These findings suggest that patient quality of life is related to COPD exacerbation frequency.

Aged↗
PubMed2006

Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease.

IMPACT: This study explores the use of measuring plasma biomarkers at exacerbation of chronic obstructive pulmonary disease (COPD), providing insight into the underlying pathogenesis of these important events. RATIONALE: The use of measuring C-reactive protein (CRP) to confirm exacerbation, or to assess exacerbation severity, in COPD is unclear. Furthermore, it is not known whether there may be more useful systemic biomarkers. OBJECTIVE: To assess the use of plasma biomarkers in confirming exacerbation and predicting exacerbation severity. METHODS: We assessed 36 biomarkers in 90 paired baseline and exacerbation plasma samples from 90 patients with COPD. The diagnosis of exacerbation fulfilled both health care use and symptom-based criteria. Biomarker concentrations were related to clinical indices of exacerbation severity. Interrelationships between biomarkers were examined to gain information on mechanisms of systemic inflammation at exacerbation of COPD. MEASUREMENTS AND MAIN RESULTS: To confirm the diagnosis of exacerbation, the most selective biomarker was CRP. However, this was neither sufficiently sensitive nor specific alone (area under the receiver operating characteristic curve [AUC], 0.73; 95% confidence interval, 0.66-0.80). The combination of CRP with any one increased major exacerbation symptom recorded by the patient on that day (dyspnea, sputum volume, or sputum purulence) significantly increased the AUC to 0.88 (95% confidence interval, 0.82-0.93; p<0.0001). There were no significant relationships between biomarker concentrations and clinical indices of exacerbation severity. Interrelationships between biomarkers suggest that the acute-phase response is related, separately, to monocytic and lymphocytic-neutrophilic pathways. CONCLUSIONS: Plasma CRP concentration, in the presence of a major exacerbation symptom, is useful in the confirmation of COPD exacerbation. Systemic biomarkers were not helpful in predicting exacerbation severity. The acute-phase response at exacerbation was most strongly related to indices of monocyte function.

Aged↗
PubMed2006

Inflammatory changes, recovery and recurrence at COPD exacerbation.

Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased airway and systemic inflammation, though relationships between exacerbation recovery, recurrent exacerbation and inflammation have not been previously reported. In the present study, inflammatory changes at COPD exacerbations were related to clinical nonrecovery and recurrent exacerbations within 50 days. Serum interleukin (IL)-6, C-reactive protein (CRP), sputum IL-6 and IL-8 were measured in 73 COPD patients when stable, at exacerbation and at 7, 14 and 35 days post-exacerbation. In 23% of patients, symptoms did not recover to baseline by day 35. These patients had persistently higher levels of serum CRP during the recovery period. A total of 22% of the patients who had recurrent exacerbations within 50 days had significantly higher levels of serum CRP at day 14, compared with those without recurrences: 8.8 mg.L(-1) versus 3.4 mg.L(-1). Frequent exacerbators had a smaller reduction in systemic inflammation between exacerbation onset and day 35 compared with infrequent exacerbators. Nonrecovery of symptoms at chronic obstructive pulmonary disease exacerbation is associated with persistently heightened systemic inflammation. The time course of systemic inflammation following exacerbation is different between frequent and infrequent exacerbators. A high serum C-reactive protein concentration 14 days after an index exacerbation may be used as a predictor of recurrent exacerbations within 50 days.

Administration, Inhalation↗
PubMed2005

Epidemiological relationships between the common cold and exacerbation frequency in COPD.

Higher exacerbation incidence rates in chronic obstructive pulmonary disease (COPD) are associated with more rapid decline in lung function and poorer quality of life, yet the mechanisms determining susceptibility to exacerbation remain ill-defined. The same viruses responsible for common colds are frequently isolated during exacerbations. The current authors hypothesised that exacerbation frequency may be associated with an increased frequency of colds, and investigated whether increased exacerbation frequency was associated with increased acquisition of colds, or a greater likelihood of exacerbation once a cold has been acquired. A total of 150 patients with COPD completed diary cards recording peak expiratory flow, and respiratory and coryzal symptoms for a median 1,047 days. Annual cold and exacerbation incidence rates (cold and exacerbation frequency) were calculated, and the relationships between these variables were investigated. This analysis is based on 1,005 colds and 1,493 exacerbations. Frequent exacerbators (i.e. those whose exacerbation frequency was greater than the median) experienced significantly more colds than infrequent exacerbators (1.73 versus 0.94.yr(-1)). The likelihood of exacerbation during a cold was unaffected by exacerbation frequency. Patients experiencing frequent colds had a significantly higher exposure to cigarette smoke (46 versus 33 pack-yrs). Exacerbation frequency in chronic obstructive pulmonary disease is associated with an increased frequency of acquiring the common cold, rather than an increased propensity to exacerbation once a cold has been acquired.

Aged↗
PubMed2006

Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations.

RATIONALE: Severe exacerbations of chronic obstructive pulmonary disease (COPD) are major causes of health care costs mostly related to hospitalization. The role of infections in COPD exacerbations is controversial. OBJECTIVES: We investigated whether COPD exacerbations requiring hospitalization are associated with viral and/or bacterial infection and evaluated relationships among infection, exacerbation severity, assessed by reduction of FEV1, and specific patterns of airway inflammation. METHODS: We examined 64 patients with COPD when hospitalized for exacerbations, and when in stable convalescence. We measured lung function, blood gases, and exhaled nitric oxide, and examined sputum for inflammation and for viral and bacterial infection. RESULTS: Exacerbations were associated with impaired lung function (p < 0.01) and increased sputum neutrophilia (p < 0.001). Viral and/or bacterial infection was detected in 78% of exacerbations: viruses in 48.4% (6.2% when stable, p < 0.001) and bacteria in 54.7% (37.5% when stable, p = 0.08). Patients with infectious exacerbations (29.7% bacterial, 23.4% viral, 25% viral/bacterial coinfection) had longer hospitalizations (p < 0.02) and greater impairment of several measures of lung function (all p < 0.05) than those with noninfectious exacerbations. Patients with exacerbations with coinfection had more marked lung function impairment (p < 0.02) and longer hospitalizations (p = 0.001). Sputum neutrophils were increased in all exacerbations (p < 0.001) and were related to their severity (p < 0.001), independently of the association with viral or bacterial infections; sputum eosinophils were increased during (p < 0.001) virus-associated exacerbations. CONCLUSIONS: Respiratory infections are associated with the majority of COPD exacerbations and their severity, especially those with viral/bacterial coinfection. Airway neutrophilia is related to exacerbation severity regardless of viral and/or bacterial infections. Eosinophilia is a good predictor of viral exacerbations.

Aged↗
PubMed2001

Mechanisms of exacerbations.

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Some patients are particularly susceptible to develop frequent exacerbations; exacerbation frequency being an important determinant of health related quality of life. Patients with frequent exacerbations (three or more exacerbations per year) have increased induced sputum cytokine interleukin (IL)-6 and IL-8 levels when stable, suggesting that frequent exacerbation is associated with increased airway inflammatory changes. Respiratory viral infections are a major cause of COPD exacerbations, with upper respiratory tract infections (colds) being associated with two-thirds of COPD exacerbations. Rhinovirus has been detected in induced sputum by PCR in 25% of exacerbations, suggesting that rhinovirus may directly infect the lower airway triggering exacerbation. The presence of an upper respiratory tract infection leads to a longer symptom recovery time at exacerbation. At exacerbation induced sputum IL-6 levels were increased compared to stable, though there were no significant increases in IL-8 or sputum cell counts. Sputum IL-6 levels were found to be higher in those patients with symptoms of a common cold. Increased airway eosinophilia has been also found at exacerbation. Other factors including bacterial colonization of the airways, temperature and interactions with environmental pollutants may also play a role in COPD exacerbation.

Animals↗
PubMed2000

Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease.

Although exacerbations of chronic obstructive pulmonary disease (COPD) are associated with symptomatic and physiological deterioration, little is known of the time course and duration of these changes. We have studied symptoms and lung function changes associated with COPD exacerbations to determine factors affecting recovery from exacerbation. A cohort of 101 patients with moderate to severe COPD (mean FEV(1) 41.9% predicted) were studied over a period of 2.5 yr and regularly followed when stable and during 504 exacerbations. Patients recorded daily morning peak expiratory flow rate (PEFR) and changes in respiratory symptoms on diary cards. A subgroup of 34 patients also recorded daily spirometry. Exacerbations were defined by major symptoms (increased dyspnea, increased sputum purulence, increased sputum volume) and minor symptoms. Before onset of exacerbation there was deterioration in the symptoms of dyspnea, sore throat, cough, and symptoms of a common cold (all p < 0.05), but not lung function. Larger falls in PEFR were associated with symptoms of increased dyspnea (p = 0.014), colds (p = 0.047), or increased wheeze (p = 0.009) at exacerbation. Median recovery times were 6 (interquartile range [IQR] 1 to 14) d for PEFR and 7 (IQR 4 to 14) d for daily total symptom score. Recovery of PEFR to baseline values was complete in only 75.2% of exacerbations at 35 d, whereas in 7.1% of exacerbations at 91 d PEFR recovery had not occurred. In the 404 exacerbations where recovery of PEFR to baseline values was complete at 91 d, increased dyspnea and colds at onset of exacerbation were associated with prolonged recovery times (p < 0.001 in both cases). Symptom changes during exacerbation do not closely reflect those of lung function, but their increase may predict exacerbation, with dyspnea or colds characterizing the more severe. Recovery is incomplete in a significant proportion of COPD exacerbations.

Aged↗
PubMed2005

Health-related QOL in acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease: a review of the literature.

There is a lack of emphasis on health-related QOL (HR-QOL) changes associated with acute exacerbation of chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD). The aim of this review is to examine the use of HR-QOL instruments to evaluate acute exacerbation of CB or COPD, so as to form recommendations for future research.A literature search of papers published between 1966 and July 2003 identified more than 300 articles that used acute exacerbation of CB or COPD as the search term. However, only 21 of these studies employed HR-QOL measures as predictors of outcome or in the assessment of the impact, evolution or treatment of acute exacerbations of COPD or CB. A variety of HR-QOL measures were used, both generic and disease specific. The disease-specific St George's Respiratory Questionnaire (SGRQ), devised for patients with stable CB and with a recall period of 1-12 months, was the most widely used measure, with the Chronic Respiratory disease Questionnaire (CRQ) and the Baseline and Transitional Dyspnoea Index (BDI, TDI) being the only other disease-specific measures used. Most measures, both generic and disease specific, performed adequately when used during acute exacerbation of CB or COPD and indicated poor HR-QOL during acute exacerbation, which improved on resolution of the exacerbation. Relationships were evident between HR-QOL during an acute exacerbation and various outcomes, including post-exacerbation functional status, hospital re- admission for acute exacerbation or COPD, and mortality. There is a need for studies of treatments for acute exacerbation of CB or COPD to include an appropriate HR-QOL instrument to aid in the stratification of patients so as to target the right treatment to the right patient group. While a new instrument could be developed to measure HR-QOL during acute exacerbation of CB or COPD, currently available disease-specific measures such as the CRQ and the SGRQ appear to be acceptable to patients during acute exacerbation. However, the recall period of the SGRQ symptoms component should be shortened to make it more appropriate for use during acute exacerbation.

Animals↗
PubMed2005

[Cost and management of asthma exacerbations in Spanish hospitals (COAX study in hospital services)].

OBJECTIVE: The prevalence and associated health cost of asthma have been increasing in developed countries, and 70% of the overall disease cost is due to exacerbations. The primary objective of this study was to determine the hospital cost of an asthma exacerbation in Spain. The secondary objective was to determine what maintenance treatments patients were using to control asthma before the exacerbation and how the exacerbation was treated. The study formed part of a broader study (COAX II), with the same objectives in each of the 8 participating European countries. PATIENTS AND METHODS: Prospective observational study that enrolled 126 patients with an asthma exacerbation treated in the usual way in 6 Spanish hospitals over a 3-month period (from January 1 to March 31, 2000). RESULTS: According to the criteria of the Global Initiative for Asthma, 33.3% of the exacerbations were mild, 38.9% moderate, 26.2% severe, and 1.6% were associated with risk of imminent respiratory arrest. Use of corticosteroids was widespread among patients with moderate and severe asthma, but only 68% of the patients with severe asthma used long-acting beta2 agonists. The mean cost was 1555.70 Euros (95% confidence interval [CI], 1237.60 Euros-1907.00 Euros), of which 93.8% (1460.60 Euros; 95% CI, 1152.50 Euros-1779.40 Euros) was due to direct costs, and 6.2% (95.10 Euros; 95% CI, 35.50 Euros-177.00 Euros) to indirect costs. Cost rose with increasing severity of the exacerbation--292.60 Euros for a mild exacerbation, 1230.50 Euros for a moderate exacerbation, and 3543.10 Euros for a severe exacerbation. CONCLUSIONS: The mean cost was 1555.70 Euros. The costs of moderate and severe exacerbations were 4 and 12 times that of a mild exacerbation, respectively. Long-acting beta2 agonists were less widely used than recommended by the guidelines for treatment of moderate and severe persistent asthma leading to asthma exacerbations.

Adrenal Cortex Hormones↗
PubMed2002

The costs of exacerbations in chronic obstructive pulmonary disease (COPD).

Exacerbations are the key drivers in the costs of chronic obstructive pulmonary disease (COPD). The objective was to examine the costs of COPD exacerbations in relation to differing degrees of severity of exacerbations and of COPD. We identified 202 subjects with COPD, defined according to the BTS and ERS criteria. Exacerbations were divided into mild (self-managed), mild/moderate (telephone contact with a health-care centre and/or the use of antibiotics/systemic corticosteroids), moderate (health-care centre visits) and severe (emergency care visit or hospital admission). Exacerbations were identified by sending the subjects a letter inquiring whether they had any additional respiratory problems or influenza the previous winter. At least one exacerbation was reported by 61 subjects, who were then interviewed about resource use for these events. The average health-care costs per exacerbation were SEK 120 (95% C=39-246), SEK 354 (252-475), SEK 2111 (1673-2612) and SEK 21852 (14436-29825) for mild, mild/moderate, moderate and severe exacerbations, respectively. Subjects with impaired lung function experienced more severe exacerbations, which was also reflected in the cost of exacerbations per severity of the disease during the 4 1/2 month study period (ranging from SEK 224 for mild to SEK 13708 for severe cases, median SEK 940). Exacerbations account for 35-45% of the total per capita health-care costs for COPD. In conclusion, costs varied considerably with the severity of the exacerbation as well as with the severity of COPD. The prevention of moderate-to-severe exacerbations could be very cost-effective and improve the quality of life.

Acute Disease↗
PubMed2001

Addition of salmeterol to low-dose fluticasone versus higher-dose fluticasone: an analysis of asthma exacerbations.

BACKGROUND: Adding salmeterol to low-dose fluticasone propionate (FP) produces greater improvements in pulmonary function and symptom control than increasing the dose of FP in patients who remain symptomatic with low-dose FP. OBJECTIVE: We sought to compare the rates and characteristics of asthma exacerbations in patients after adding salmeterol to low-dose FP with the rates and characteristics of exacerbations in patients receiving higher dose FP. METHODS: In 2 multicenter, double-blind studies, 925 patients 12 years of age and older receiving 88 microg twice daily FP randomly received either 42 microg of salmeterol and 88 microg of FP or an increased dose of FP (220 microg) twice daily for 24 weeks. Exacerbation rates and clinical measures of asthma worsening were assessed for all patients who experienced an asthma exacerbation. RESULTS: The addition of salmeterol resulted in a significantly lower rate and number of exacerbations compared with higher dose FP. A total of 41 (8.8%) patients experienced 47 exacerbations with the addition of salmeterol compared with 63 (13.8%) patients with 75 exacerbations in the group receiving increased-dose FP (P =.017). Salmeterol plus low-dose FP was significantly more protective than increased-dose FP in preventing asthma exacerbations, as assessed by the time to first exacerbation (P <.05). In both groups clinical indicators of worsening asthma showed parallel changes before asthma exacerbation, and greater improvements were observed after exacerbation with salmeterol compared with higher dose FP. CONCLUSION: Salmeterol plus low-dose FP was more effective than higher dose FP alone in reducing asthma exacerbations in patients with persistent asthma. The ability to detect deteriorating asthma and the severity of exacerbation was similar between groups.

Acute Disease↗