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PubMed2004

Control and exacerbation of asthma: a survey of more than 3000 French physicians.

BACKGROUND: Asthma control and prevention of exacerbations are primary objectives for asthma care. However there is a lack of universal definition of these notions which may therefore have a different meaning according to the physician's practice. METHODS: In the present survey, 1805 general practitioners, 551 pulmonologists, 176 allergologists and 470 resuscitation/emergency care physicians were randomly selected in fall 2001 and asked to answer one question on asthma control and three questions on asthma exacerbation. RESULTS: Regarding asthma control, the presence of minimum symptoms was the primary criterion for asthma specialists (pulmonologists and allergologists), while a normal respiratory function was first considered by nonspecialist physicians (general practitioners and emergency care physicians). The first criterion of mild exacerbation for asthma specialists was the occurrence during at least 2 days of an increase in the frequency of dyspnoea and/or the use of short-acting bronchodilators. For nonspecialist physicians, dyspnoea affecting daily activities and/or sleeping was the preferred notion. Hospitalization was unanimously recognized as the first criterion for severe exacerbations. A decrease in peak expiratory flow of more than 30% below the baseline value on two consecutive days and an episode requiring systemic corticosteroids were the next criteria. CONCLUSIONS: This survey emphasizes the complexity of the notions of asthma control and exacerbation and provides novel informations to orient continuing education programmes.

Asthma↗

PubMed2005

The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma.

BACKGROUND: Patients with severe persistent asthma who are inadequately controlled despite treatment according to current asthma management guidelines have a significant unmet medical need. Such patients are at high risk of serious exacerbations and asthma-related mortality. METHODS: Here, we pooled data from seven studies to determine the effect of omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, on asthma exacerbations in patients with severe persistent asthma. Omalizumab was added to current asthma therapy and compared with placebo (in five double-blind studies) or with current asthma therapy alone (in two open-label studies). The studies included 4308 patients (2511 treated with omalizumab), 93% of whom had severe persistent asthma according to the Global Initiative for Asthma (GINA) 2002 classification. Using the Poisson regression model, results were calculated as the ratio of treatment effect (omalizumab : control) on the standardized exacerbation rate per year. RESULTS: Omalizumab significantly reduced the rate of asthma exacerbations by 38% (P < 0.0001 vs control) and the rate of total emergency visits by 47% (P < 0.0001 vs control). Analysis of demographic subgroups showed that the efficacy of omalizumab on asthma exacerbations was unaffected by patient age, gender, baseline serum IgE (split by median) or by 2- or 4-weekly dosing schedule, although benefit in absolute terms appeared to be greatest in patients with more severe asthma, defined by a lower value of percentage predicted forced expiratory volume in 1 s (FEV(1)) at baseline. CONCLUSIONS: These results suggest that omalizumab may fulfil an important need in patients with severe persistent asthma, many of whom are not adequately controlled on current therapy.

Anti-Asthmatic Agents↗

PubMed2007

Open-label, randomized comparison trial of long-term outcomes of levofloxacin versus standard antibiotic therapy in acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: This study investigated whether treating acute exacerbations of COPD (AE-COPD) with levofloxacin modifies the long-term outcome of COPD patients in comparison with standard antibiotic regimens. METHODS: A 6-month open-label clinical trial of AE-COPD patients compared the outcomes of treating with levofloxacin versus standard therapy (clarithromycin, cefuroxime, or amoxicillin/clavulanate) at recommended doses for 10 days. Several variables were analysed: pulse oximetry, FEV1, health-related quality of life, infection-free interval, number of exacerbations, hospitalizations due to an exacerbation and mortality. RESULTS: Of the 116 patients initially enrolled, completion or withdrawal information was available for 50 patients in the levofloxacin arm and 52 in the standard therapy arm. At the end of the study, there were no differences in mortality (17.8% vs. 22.9%, P = 0.53), number of exacerbations (33 vs. 41, P = 0.40), pulse oximetry (median 91.71% vs. 92.46%, P = 0.18), FEV1 (median 51.31% vs. 47.14%, P = 0.30), health-related quality of life (median 8.63 vs. 10.75, P = 0.94) and infection-free interval (median 112 vs. 101 days, P = 0.72), for the levofloxacin and standard therapy, respectively. However, 12 out of 33 (33.6%) exacerbations treated with levofloxacin required in-hospital management versus 27 out of 41 (65.8%) treated with standard therapy (P = 0.02). CONCLUSION: This preliminary study suggests that 10-day treatment of AE-COPD with levofloxacin is associated with a reduction in hospitalizations compared with standard antibiotics despite there being no significant benefit in other outcome variables.

Amoxicillin↗

PubMed1986

The role of delta superinfection in acute exacerbations of chronic type B hepatitis.

Serum specimens collected from patients with chronic type B hepatitis during their acute exacerbations were studied with radioimmunoassay for serological markers of delta (delta) agent infection. Serum delta antigen was negative in all 56 hepatitis B e antigen (HBeAg)-positive and 25 anti-HBe-positive acute exacerbations. Two (3.6%) HBeAg-positive and five (20%) anti-HBe-positive acute exacerbations were found to be positive for both IgG anti-delta and IgM anti-delta. The incidence in anti-HBe-positive patients was significantly higher than in HBeAg-positive patients. These results indicated that some of the acute exacerbations, particularly in anti-HBe-positive phase, could be attributed to delta-superinfection. However, acute exacerbations preceding HBeAg/anti-HBe seroconversion were not associated with delta-superinfection.

Hepatitis Antibodies↗

PubMed1994

Fluctuations in viremia, aminotransferases and IgM antibody to hepatitis B core antigen in chronic hepatitis B patients with disease exacerbations.

We studied the relationships between the serum levels of viremia, aminotransferases and IgM anti-HBc, measured by monthly quantitative assays, in 52 untreated chronic hepatitis B patients (41 anti-HBe+, 11 HBeAg+) followed up for 12-20 months. Forty hepatitis exacerbations were observed in 17/41 anti-HBe+ (41.5%) and in 6/11 HBeAg+ patients (54.5%) (p = NS); all but one were clinically asymptomatic. We analyzed the fluctuations in the serum levels of the three parameters before, during and after the hepatitis exacerbations and found this chronological sequence of events in 96.2% of them: HBV-DNA increase-->ALT flare-->IgM anti-HBc increase. These results suggest that both antiviral immune reactions and ALT flares were triggered by quantitative variations in viremia. HBV-DNA baseline levels before flares were lower in anti-HBe+ (3.9 +/- 1.2 pg/ml) than in HBeAg+ patients (35.3 +/- 5.4 pg/ml) (p < 0.0001) and there was an inverse correlation between basal values and viremia level increases at the time of disease exacerbations (p < 0.001). This suggests that for a hepatitis exacerbation to occur, low basal viremia needed to increase markedly, while moderate increases in HBV-DNA serum levels were sufficient to trigger ALT flares in patients with elevated basal viremia. In conclusion, asymptomatic hepatitis B exacerbations are frequent in the natural history of chronic HBV infection, and monthly monitoring of HBV-DNA, ALT and IgM anti-HBc appears to be a suitable method to evaluate their frequencies and entities. This method can be a helpful guide for clinical and therapeutic decision-making in the single patient with chronic hepatitis B.

Adult↗

PubMed2001

[Acute exacerbations due to Streptococcus pneumoniae in chronic lower respiratory tract infections during long-term macrolide therapy].

In Japan, long-term 14-membered macrolide administration is chosen as a first line therapy against chronic lower respiratory tract infections (CLRTIs) such as diffuse panbronchiolitis, bronchiectasis and chronic bronchitis. However, sometimes acute exacerbations occur in these cases, even if therapy is effective. We investigated 18 episodes of CLRTIs exacerbations that were caused by Streptococcus pneumoniae during long-term macrolides therapy from 1991 to 1999 to clarify the clinical features and prevalence of antimicrobial resistance in S. pneumoniae. Exacerbations did not occur only in winter season, but also in other seasons. Among 18 episodes of exacerbation, only 7 episodes (39%) revealed infiltration in chest roentogenogram and few episodes revealed marked elevations of inflammation markers in laboratory data. Intermediate resistance or resistance rates of S. pneumoniae isolated from sputum or transtracheal aspiration were 100% to erythromycin, 67% to clindamycin or minocycline, 11% to ampicillin, and 0% to cephazoline or imipenem. Coresistance to erythromycin, clindamycin and minocycline was seen in a half of the episodes. Resistance was not correlated with the duration of macrolides administration. All episodes were mainly treated with beta-lactam agents or fluoroquinolones and cured successfully. These findings suggest that acute exacerbations in CLRTIs caused by S. pneumoniae during long-term macrolides therapy do not reveal severe clinical aspects and can be treated successfully at present, but attention should be paid to the trend of antibiotic susceptibility in S. pneumoniae.

Adolescent↗

PubMed1998

Treatment of acute asthmatic exacerbations with an increased dose of inhaled steroid.

OBJECTIVE: To investigate the efficacy of an increased dose of inhaled steroid used within the context of an asthma self management plan for treating exacerbations of asthma. DESIGN: Randomised, double blind, placebo controlled, crossover trial. METHODS: Twenty eight children aged 6-14 years with asthma of mild to moderate severity were studied for six months. Eighteen pairs of exacerbations were available for analysis, during which subjects took an increased dose of inhaled steroids or continued on the same dose. RESULTS: There was no significant difference between increasing inhaled steroids or placebo on morning or evening peak expiratory flow rates (PEFRs), diurnal peak flow variability, or symptom scores in the two weeks following an asthma exacerbation. Difference (95% confidence intervals) in baseline PEFR on days 1-3 were 3.4% (-3.5% to 10.4%) and -0.9% (-4.7% to 2.9%) for inhaled steroid and placebo, respectively. Spirometric function and the parents' opinion of the effectiveness of asthma medications at each exacerbation were also not significantly different between inhaled steroid or placebo. CONCLUSION: This study suggests that increasing the dose of inhaled steroids at the onset of an exacerbation of asthma is ineffective and should not be included in asthma self management plans.

Acute Disease↗

PubMed2002

Cough, airway inflammation, and mild asthma exacerbation.

BACKGROUND: Prospective data on the temporal relation between cough, asthma symptoms, and airway inflammation in childhood asthma is unavailable. AIMS AND METHODS: Using several clinical (diary, quality of life), lung function (FEV(1), FEV(1) variability, airway hyperresponsiveness), cough (diary, cough receptor sensitivity (CRS)), and inflammatory markers (sputum interleukin 8, eosinophilic cationic protein (ECP), myeloperoxidase; and serum ECP) of asthma severity, we prospectively described the course of these markers in children with asthma during a non-acute, acute, and resolution phase. A total of 21 children with asthma underwent these baseline tests; 11 were retested during days 1, 3, 7, and 28 of an exacerbation. RESULTS: Asthma exacerbations were characterised by increased asthma and cough symptoms and eosinophilic inflammation. Sputum ECP showed the largest increase and peaked later than clinical scores. Asthma scores consistently related to cough score only early in the exacerbation. Neither CRS nor cough scores related to any inflammatory marker. CONCLUSION: In mild asthma exacerbations, eosinophilic inflammation is dominant. In asthmatic children who cough as a dominant symptom, cough heralds the onset of an exacerbation and increased eosinophilic inflammation, but cough scores and CRS do not reflect eosinophilic airway inflammation.

Acute Disease↗

PubMed1989

Systemic lupus erythematosus. II. Observations on the occurrence of exacerbations in the disease course: Dutch experience with 110 patients studied prospectively.

The incidence of exacerbations in the disease course was investigated in 110 patients with systemic lupus erythematosus (SLE) who were studied prospectively at our institute for lupus research. At the time of disease onset and diagnosis the male patients were much older than the female patients (about 10 years); exacerbation frequency during follow up was increased in the male patients. The follow up data showed that if a patient with SLE was prone to develop an exacerbation this mostly took place within the first five years of follow up. It could be calculated that after fulfilling the American Rheumatism Association criteria only 56% (62/110) of the patients developed a subsequent exacerbation. Features at the time of diagnosis, distinguishing those patients who developed a subsequent exacerbation from those who did not, were haemolytic anaemia, the presence of anti-Sm antibodies, and a falsely positive serological test for syphilis. At the time of diagnosis, however, the prevalences of these features were low; for haemolytic anaemia, anti-Sm antibodies, and a falsely positive serological test for syphilis they amounted to 40%, 5%, and 12% respectively.

Adult↗

PubMed1993

Respiratory viruses and exacerbations of asthma in adults.

OBJECTIVE: To study the role of respiratory viruses in exacerbations of asthma in adults. DESIGN: Longitudinal study of 138 adults with asthma. SETTING: Leicestershire Health Authority. SUBJECTS: 48 men and 90 women 19-46 years of age with a mean duration of wheeze of 19.6 years. 75% received regular treatment with bronchodilators; 89% gave a history of eczema, hay fever, allergic rhinitis, nasal polyps, or allergies; 38% had been admitted to hospital with asthma. MAIN OUTCOME MEASURES: Symptomatic colds and asthma exacerbations; objective exacerbations of asthma with > or = 50 l/min reduction in mean peak expiratory flow rate when morning and night time readings on days 1-7 after onset of symptoms were compared with rates during an asymptomatic control period; laboratory confirmed respiratory tract infections. RESULTS: Colds were reported in 80% (223/280) of episodes with symptoms of wheeze, chest tightness, or breathlessness, and 89% (223/250) of colds were associated with asthma symptoms. 24% of 115 laboratory confirmed non-bacterial infections were associated with reductions in mean peak expiratory flow rate > or = 50 l/min through days 1-7 and 48% had mean decreases > or = 25 l/min. 44% of episodes with mean decreases in flow rate > or = 50 l/min were associated with laboratory confirmed infections. Infections with rhinoviruses, coronaviruses OC43 and 229E, influenza B, respiratory syncytial virus, parainfluenza virus, and chlamydia were all associated with objective evidence of an exacerbation of asthma. CONCLUSIONS: These findings show that asthma symptoms and reductions in peak flow are often associated with colds and respiratory viruses; respiratory virus infections commonly cause or are associated with exacerbations of asthma in adults.

Adult↗

PubMed2006

Asthma exacerbations . 4: Prevention.

Asthma exacerbations are common. They account for a significant morbidity and contribute a disproportionate amount to the cost of asthma management. The optimal strategies for the prevention of asthma exacerbations include the early introduction of anti-inflammatory treatment-most commonly, low dose inhaled corticosteroids. This should be coupled with a structured education programme which has a written action plan as an integral component. Where patients continue to be poorly controlled, the addition of a long acting beta agonist should be considered. The latter should not be used as monotherapy and should always be used with inhaled corticosteroids. Atopic patients with a history of repeated exacerbations, especially if they are steroid dependent and with a raised IgE, may be considered as potential candidates for omalizumab. In the early stages of an asthma exacerbation, doubling the dose of inhaled corticosteroids has been shown to be ineffective. The ideal strategy for the management of worsening asthma in patients on combination treatment, especially salmeterol and fluticasone, is uncertain. There is an emerging body of evidence for strategies on how to prevent progression to an exacerbation in patients taking a combination of budesonide and formoterol.

Administration, Inhalation↗

PubMed2006

Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol.

BACKGROUND: The homozygous presence of the arginine-16 variant of the beta(2) adrenoceptor gene ADRB2 reverses the benefits from the regular use of short acting beta(2) agonists in asthmatic adults compared with the homozygous glycine-16 genotype. We studied the effect of this polymorphic variation on asthma exacerbations in children and young adults and its relation to long acting beta(2) agonists. METHODS: A cross-sectional survey was undertaken using electronic records, direct interviews, and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples of 546 children and young asthmatics attending paediatric and young adult asthma clinics in Tayside, Scotland during 2004-5. The primary outcome measure was asthma exacerbations over the previous 6 months. RESULTS: There was an increased hazard of asthma exacerbations across all treatment steps of the British Thoracic Society (BTS) asthma guidelines when the homozygous genotypes Arg/Arg and Gly/Gly were compared (OR 2.05, 95% CI 1.19 to 3.53, p = 0.010), particularly in patients treated with salmeterol (OR 3.40, 95% CI 1.19 to 9.40, p = 0.022). The Glu27Gln polymorphism had no significant effect on asthma exacerbations in any treatment group. CONCLUSIONS: The arginine-16 genotype of ADRB2 predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. This may be explained by genotype selective salmeterol induced downregulation and impaired receptor coupling, and associated subsensitivity of the response.

Adolescent↗

PubMed1979

Relationship of bacterial and viral infections to exacerbations of asthma.

Fifty-one asthmatic patients were followed for up to 18 months. During this time 111 exacerbations of wheeze were recorded. Involvement by pathogenic respiratory bacteria and viruses was looked for directly by culture and indirectly by antibody studies. Proof of infection was found in only 12 (10.8%) of the 111 exacerbations. Only eight patients provided sputum samples. Potential bacterial pathogens were found in four. Viruses were isolated in four of 27 exacerbation specimens; significant rises in specific viral antibody titres occurred in three. Six patients developed precipitating antibody to respiratory bacteria over the study but only one in relation to an exacerbation. The study therefore indicated that the great majority of exacerbations of asthma in these patients were not due to respiratory tract infection.

Adult↗

PubMed2004

[Effect of immunomodulator AM3 on the exacerbations in patients with chronic bronchitis: a systematic review of controlled trials].

OBJECTIVE: Analyze the effect of AM3, an oral immunomodulator, on the exacerbations and on the use of antibiotics in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Systematic search of controlled clinical trials that used AM3 in some treatment group and that included data on the clinical effects of this drug on patients with COPD. SELECTED VARIABLES: Nine studies were detected in which the clinical effectiveness of AM3 was evaluated in relation to the number of infectious exacerbations, their length, and the length of the antibiotic treatment used. RESULTS: In comparison with placebo group, the average number of excaerbations suffered by the patients treated with AM3 declined significantly in 0.31 units (p < 0.001; 95% confidence interval: 0.20-0.42), without heterogeneity among the different studies (Q = 6.62; p > 0.43). With regard to the average length of the exacerbations and the average length of the antibiotic treatment used for the exacerbations, both variables declined significantly in the group treated with AM3 (3.10 days, p < 0.001, and 8.07 days, p < 0.001, respectively) but this positive effect could not be confirmed because trials were close to heterogeneity. CONCLUSIONS: The results of this systematic review show that AM3 has a clinical effect in the prevention of exacerbations of COPD patients because reduces significantly their number. This could be related to a slowing in the progression of the deterioration in the respiratory function with a potential impact on the quality of life of the patients. Furthermore, these data imply a positive therapeutic result and a possible decline in development of bacterial resistances secondary to the frequent and indiscriminate use of antibiotics in these patients.

Adjuvants, Immunologic↗

PubMed2002

The premenstrual period and exacerbations in multiple sclerosis.

The aim of this study was to assess whether an association exists between the premenstrual period and exacerbations of multiple sclerosis (MS). The subjects were 56 premenopausal patients with relapsing MS and a regular menstrual cycle. Data over the previous 2 years were gathered from a structured MS database and a comprehensive questionnaire. 42% had exacerbations starting in the premenstrual phase. Within this group the proportion of premenstrual exacerbations was significantly higher than in the remaining period of the menstrual cycle, and in 45% all exacerbations had started during the premenstrual phase. There was no relationship with the premenstrual syndrome, and there was no protective effect of oral contraceptives. Our results suggest that the premenstrual period triggers exacerbations in a subgroup of females with MS.

Adult↗

PubMed2004

Mechanism of acute pancreatitis exacerbation by enteral bile-pancreatic juice exclusion.

Using an original model, the donor rat model, we previously showed that bile-pancreatic juice exclusion from gut exacerbates ligation-induced acute pancreatitis. Here, we examine the mechanism by which bile-pancreatic juice exclusion from gut exacerbates acute pancreatitis. In the first part of the study we test the hypothesis that Na taurocholate and trypsin are components of bile-pancreatic juice that exacerbate acute pancreatitis when excluded. Our experiments show that combined replacement of Na taurocholate and trypsin ameliorates acute pancreatitis. In the second part of the study we test the hypothesis that bile-pancreatic juice exclusion from gut exacerbates acute pancreatitis via combined CCK-A and cholinergic receptor pathways. Our experiments show that combined CCK-A and cholinergic receptor blockade significantly ameliorates acute pancreatitis while blockade of either receptor alone does not. We conclude that bile-pancreatic juice exclusion-induced exacerbation of ligation-induced acute pancreatitis involves a neurohormonal duodenal response to exclusion of trypsin and Na taurocholate resulting in acinar cell hyperstimulation via combined CCK-A and cholinergic receptor-mediated pathways.

Amylases↗

PubMed1996

Prevention of acute exacerbations of chronic obstructive bronchitis with carbocysteine lysine salt monohydrate: a multicenter, double-blind, placebo-controlled trial.

The efficacy and safety of carbocysteine lysine salt monohydrate (SCMC-Lys) in the prevention of acute exacerbations associated with chronic obstructive bronchitis were evaluated in a multicenter double-blind, placebo-controlled, parallel group trial in 662 outpatients. After a 1-month run-in period, patients were randomized to three groups and assigned to receive one of the following oral treatments: continuous SCMC-Lys 2.7 g once daily, intermittent SCMC-Lys at the same dosage (1-week courses alternating with 1-week intervals on placebo) or placebo. Each treatment lasted for 6 months and spanned the cooler months of the year. Evaluation was based on a daily recording of relevant clinical symptoms and signs and subsequent evaluation of the collected data by three blinded independent physicians. A total of 146 patients (23%) failed to complete the 6-month treatment (mostly due to difficulties in complying with protocol requirements), without clear-cut differences in the dropout rate in the three groups. An intention-to-treat analysis revealed that the incidence of patients without exacerbations in the group assigned to continuous SCMC-Lys treatment was significantly higher than in the placebo-treated group (p < 0.001). The total number of patients with at least one exacerbation was 66 (29.6%) in the group treated with continuous SCMC-Lys compared with 100 (45.9%) with placebo. In the former group the time between initiation of treatment and first exacerbation was significantly prolonged. The average number of days with acute respiratory illness was significantly decreased in the group receiving continuous SCMC-Lys compared with the group receiving placebo, and this was associated with a significant reduction in the antibiotic consumption during the trial period. In patients assigned to intermittent treatment, results of the assessed endpoints did not differ significantly from those observed in the placebo group. No serious adverse effects were reported. It is concluded that continuous administration of SCMC-Lys throughout the winter season is effective in preventing acute exacerbations in patients with chronic obstructive bronchitis and it is well tolerated.

Adult↗

PubMed1996

Changes in peak flow, symptom score, and the use of medications during acute exacerbations of asthma.

Changes in symptom score and peak expiratory flow (PEF) and the use of medications during the first acute exacerbation of asthma were studied in 41 patients and matched controls who took part in a panel study. An acute exacerbation was defined as the presence of at least one of the following: any unscheduled physician visit, visit to an emergency room, or hospitalization for treatment of asthma; a decrease in PEF by 30% from the patient's best reading; an increase in asthma symptoms during the day and night for over 48 h and not responding to usual medications; and the commencement or doubling of the dose of oral or inhaled steroids for any of the foregoing reasons. Data from -9 to -7 d before the onset of an acute exacerbation were taken as the baseline data, with which the values of the subsequent 14 d were compared. Significant increases in symptoms occurred before a significant reduction in PEF. None of the patients had a decrease of more than 30% in PEF before the onset of symptoms. Daily variation in PEF was not significantly increased from the baseline. Our results suggest that PEF monitoring is not as sensitive as a symptom diary for revealing acute exacerbations of asthma, and that a 30% decrease in PEF is too stringent a criterion for defining an acute exacerbation.

Acute Disease↗