Azithromycin for episodes with asthma-like symptoms in young children aged 1–3 years: a randomised, double-blind, placebo-controlled trial Procalcitonin guidance for reduction of antibiotic use in patients hospitalized with severe acute exacerbations of asthma: a randomized controlled study with 12-month follow-up Procalcitonin and C-Reactive Protein in Hospitalized Adult Patients With Community-Acquired Pneumonia or Exacerbation of Asthma or COPD Effect of clarithromycin on cytokines and chemokines in children with an acute exacerbation of recurrent wheezing: a double-blind, randomized, placebo-controlled trial. Procalcitonin guided antibiotic therapy of acute exacerbations of asthma: a randomized controlled trial Double-blind study of the effectiveness of a broad spectrum antibiotic in status asthmaticus. What are minimal important changes for asthma measures in a clinical trial? The effect of telithromycin in acute exacerbations of asthma. Effect of clarithromycin on acute asthma exacerbations in children: an open randomized study. ROUTINE ANTIBIOTICS IN HOSPITAL MANAGEMENT OF ACUTE ASTHMA Azithromycin for Acute Exacerbations of Asthma : The AZALEA Randomized Clinical Trial.
Summary Background Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like symptoms in young children , suggesting antibiotics as a potential treatment for such episodes . We aim ed to assess the effect of azithromycin on the duration of respiratory episodes in young children with recurrent asthma-like symptoms , hypothesising that it reduces the duration of the symptomatic period . Methods In this r and omised , double-blind , placebo-controlled trial , we recruited children aged 1–3 years , who were diagnosed with recurrent asthma-like symptoms from the Copenhagen Prospect i ve Studies on Asthma in Childhood 2010 cohort ; a birth cohort consisting of the general Danish population of Zeal and , including Copenhagen . Exclusion criteria were macrolide allergy , heart , liver , neurological , and kidney disease , and , before each treatment , one or more clinical signs of pneumonia ( respiratory frequency of ≥50 breaths per min ; fever of ≥39 ° C ; C-reactive protein concentration of ≥476·20 nmol/L [ ≥50 mg/L ] ) . Each episode of asthma-like symptoms lasting at least 3 days was r and omly allocated to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo after thorough examination by a study physician at the Copenhagen Prospect i ve Studies on Asthma research unit . Each episode was r and omly allocated independently of previous treatment from a computer-generated list of r and om numbers in blocks of ten ( generated at the Pharmacy of Glostrup ) . Investigators and children were masked until the youngest child turned 3 years of age and throughout the data validation and analysis phases . The primary outcome was duration of the respiratory episode after treatment , verified by prospect i ve daily diaries and analysed with Poisson regression . Analyses were per protocol ( excluding those without a primary outcome measure or who did not receive treatment ) . This trial is registered with Clinical Trials.gov , number NCT01233297 . Findings Between Nov 17 , 2010 , and Jan 28 , 2014 , we r and omly allocated 158 asthma-like episodes in 72 children ( 79 [ 50 % ] to azithromycin and 79 [ 50 % ] to placebo  ) . The mean duration of the episode after treatment was 3·4 days for children receiving azithromycin compared with 7·7 days for children receiving  placebo . Azithromycin  caused a significant shortening of the episode of 63·3 % ( 95 % CI 56·0–69·3 ; p<0·0001 ) . The effect size increased with early initiation of treatment , showing a reduction in episode duration of 83 % if treatment was initiated before day 6 of the episode compared with 36 % if initiated on or after day 6 ( p<0·0001 ) . We noted no differences in clinical adverse events between the azithromycin ( 18 [ 23 % ] of 78 episodes included in final analysis ) and placebo ( 24 [ 30 % ] of 79 ) groups ( p=0·30 ) , but we did not investigate bacterial resistance patterns after treatment . Interpretation Azithromycin reduced the duration of episodes of asthma-like symptoms in young children , suggesting that this drug could have a role in acute management of exacerbations . Further research is needed to disentangle the inflammatory versus antimicrobial aspects of this relation . Funding Lundbeck Foundation , Danish Ministry of Health , Danish Council for Strategic Research , Capital Region Research Foundation Introduction Patients with severe acute exacerbations of asthma often receive inappropriate antibiotic treatment . We aim ed to determine whether serum procalcitonin ( PCT ) levels can effectively and safely reduce antibiotic exposure in patients experiencing exacerbations of asthma . Methods In this r and omized controlled trial , a total of 216 patients requiring hospitalization for severe acute exacerbations of asthma were screened for eligibility to participate and 169 completed the 12-month follow-up visit . Patients were r and omized to either PCT-guided ( PCT group ) or st and ard ( control group ) antimicrobial therapy . In the control group , patients received antibiotics according to the attending physician ’s discretion ; in the PCT group , patients received antibiotics according to an algorithm based on serum PCT levels . The primary end point was antibiotic exposure ; secondary end points were clinical recovery , length of hospital stay , clinical and laboratory parameters , spirometry , number of asthma exacerbations , emergency room visits , hospitalizations and need for corticosteroid use due to asthma . Results PCT guidance reduced antibiotic prescription ( 48.9 % versus 87.8 % , respectively ; P < 0.001 ) and antibiotic exposure ( relative risk , 0.56 ; 95 % confidence interval , 0.44 to 0.70 ; P < 0.001 ) compared to st and ard therapy . There were no significant differences in clinical recovery , length of hospital stay or clinical , laboratory and spirometry outcomes in both groups . Number of asthma exacerbations , emergency room visits , hospitalizations and need for corticosteroid use due to asthma were similar during the 12-month follow-up period . Conclusion A PCT-guided strategy allows antibiotic exposure to be reduced in patients with severe acute exacerbation of asthma without apparent harm . Trial registration Chinese Clinical Trial Register ChiCTR-TRC-12002534 ( registered 26 September 2012 Background : Antibiotic overuse in respiratory illness is common and is associated with drug resistance and hospital-acquired infection . Biomarkers that can identify bacterial infections may reduce antibiotic prescription . We aim ed to compare the usefulness of the biomarkers procalcitonin and C-reactive protein ( CRP ) in patients with pneumonia or exacerbations of asthma or COPD . Methods : Patients with a diagnosis of community-acquired pneumonia or exacerbation of asthma or COPD were recruited during the winter months of 2006 to 2008 . Demographics , clinical data , and blood sample s were collected .  Procalcitonin and CRP concentrations were measured from available sera . Results : Sixty-two patients with pneumonia , 96 with asthma , and 161 with COPD were studied .  Serum procalcitonin and CRP concentrations were strongly correlated ( Spearman rank correlation coefficient [ rs ] = 0.56 , P < .001 ) . Patients with pneumonia had increased procalcitonin and CRP levels ( median [ interquartile range ] 1.27 ng/mL [ 2.36 ] , 191 mg/L [ 159 ] ) compared with those with asthma ( 0.03 ng/mL [ 0.04 ] , 9 mg/L [ 21 ] ) and COPD ( 0.05 ng/mL [ 0.06 ] , 16 mg/L [ 34 ] ) . The area under the receiver operating characteristic curve ( 95 % CI ) for distinguishing between patients with pneumonia ( antibiotics required ) and exacerbations of asthma ( antibiotics not required ) , for procalcitonin and CRP was 0.93 ( 0.88 - 0.98 ) and 0.96 ( 0.93 - 1.00 ) . A CRP value > 48 mg/L had a sensitivity of 91 % ( 95 % CI , 80%-97 % ) and specificity of 93 % ( 95 % CI , 86%-98 % ) for identifying patients with pneumonia . Conclusions : Procalcitonin and CRP levels can both independently distinguish pneumonia from exacerbations of asthma . CRP levels could be used to guide antibiotic therapy and reduce antibiotic overuse in hospitalized patients with acute respiratory illness BACKGROUND Clarithromycin is postulated to possess immunomodulatory properties in addition to its antimicrobial activity . OBJECTIVE To evaluate the effect of clarithromycin on serum and nasopharyngeal cytokine and chemokine concentrations in children with an acute exacerbation of recurrent wheezing . METHODS Children with a history of recurrent wheezing or asthma and who presented with an acute exacerbation of wheezing were enrolled in a double-blind , r and omized trial of clarithromycin vs placebo . Concentrations of tumor necrosis factor alpha ( TNF-alpha ) , interferon-gamma ( IFN-gamma ) , interleukin-1beta ( IL-1beta ) , IL-2 , IL-4 , IL-5 , IL-6 , IL-8 , IL-10 , granulocyte-macrophage colony-stimulating factor , RANTES , eotaxin , macrophage inflammatory protein 1alpha , macrophage inflammatory protein 1beta , and monocyte chemoattractant protein 1 were measured in serum and /or nasopharyngeal aspirates before , during , and after therapy . Mycoplasma pneumoniae and Chlamydophila pneumoniae infection were evaluated for by polymerase chain reaction and serologic testing . RESULTS Nasopharyngeal concentrations of TNF-alpha , IL-1beta , and IL-10 were significantly and persistently lower in children treated with clarithromycin compared with placebo . There tended to be a greater effect of clarithromycin on nasopharyngeal cytokine concentrations in patients with evidence of M. pneumoniae or C. pneumoniae infection . No significant differences were detected in serum cytokines for children treated with clarithromycin compared with placebo . CONCLUSION Clarithromycin therapy reduces mucosal TNF-alpha , IL-1beta , and IL-10 concentrations in children with an acute exacerbation of recurrent wheezing Background This r and omized controlled trial aim ed to evaluate whether the serum procalcitonin  ( PCT ) level can be utilized to guide the use of antibiotics in the treatment of acute exacerbations of asthma . Methods A total of 293 consecutive patients with suspected asthma attacks from February 2005 to July 2010 participated in this study . 225 patients completed the study . Serum PCT levels , and other inflammatory biomarkers of all patients were measured . In addition to the st and ard treatment , the control group received antibiotics according to the attending physicians ’ discretions , while the patients in the PCT group were treated with antibiotics according to serum PCT concentrations . Antibiotics usage was strongly discouraged when the PCT concentration was below 0.1 μg/L ; discouraged when the PCT concentration was between 0.1 μg/L and 0.25 μg/L ; or encouraged when the PCT concentration was above 0.25 μg/L. The primary endpoint was the determination of antibiotics usage . The second endpoints included the diagnostic accuracy of PCT and other laboratory biomarkers the effectiveness of asthma control , secondary ED visits , hospital re-admissions , repeated needs for steroids or dosage increase , needs for antibiotics , WBC count , PCT levels and FEV1 % . Results At baseline , two groups were identical regarding clinical , laboratory and symptom score . Probability of  the antibiotics usage in the PCT group ( 46.1 % ) was lower than that in the control group ( 74.8 % ) ( χ2 = 21.97 , p < 0.001 . RR = 0.561 , 95 % CI 0.441 - 0.713 ) . PCT and IL-6 showed good diagnostic significance for bacterial asthma ( r = 0.705 , p = 0.003 ) . The degrees of asthma control in patients were categorized to three levels and were comparable between the two groups at the six weeks follow-up period ( χ2 = 1.62 , p = 0.45 ) . There were no significant difference regarding other secondary outcomes ( p > 0.05 ) . Conclusions The serum PCT concentration can be used to effectively determine whether the acute asthma patients have bacterial infections in the respiratory tract , and to guide the use of antibiotics in the treatment of acute asthma exacerbations , which may substantially reduce unnecessary antibiotic use without compromising the therapeutic outcomes .Trial registration The dosage of 1:1,000 aqueous epinephrine is incorrectly given in the article by Shapiro et al. in the June issue ( Pediatrics , 53:867 , 1974 ) . The cor- rect dosage is 0.01 cc/kilo instead of 0.1 cc/kilo as given . The patient9s serum IgE level in the article by Albrecht et al. in the June issue ( Pediatrics , 53:907 , 1974 ) is incorrect . It should be given as 205 nanograms per milliliter instead of 205 mg/ml In this study , the perceptions of asthmatics to change in their disease was associated with observed changes in clinical asthma measures , in order to identify the threshold where changes in clinical asthma measures are perceivable by patients . The study included 281 asthmatic patients , aged 18 - 63 yrs , in a r and omized , placebo-controlled clinical trial of a leukotriene antagonist .  Changes were related in : 1 ) asthma symptom scores ; 2 ) inhaled beta-agonist use ; 3 ) forced expiratory volume in one second ( FEV1 ) ; and 4 ) peak expiratory flow ( PEF ) to a global question that queried overall change in asthma since starting the study drug . Additional analyses examined differences in the group reporting minimal improvement by treatment ( active treatment versus placebo ) , sex and age groups . The average minimal patient perceivable improvement for each measure was : 1 ) -0.31 points for the symptom score on a scale of 0 - 6 ; 2 ) -0.81 puffs x day(-1 ) for inhaled beta-agonist use ; 3 ) 0.23 L for FEV1 ; and 4 ) 18.79 L x min(-1 ) for PEF . In general placebo-treated patients and older patients , who reported minimal improvement , experienced less mean improvement from baseline than active-treated patients and younger patients , who reported minimal improvement . Determining the minimal patient perceivable improvement value for a measure may be helpful to interpret changes . However , interpretation should be carried out cautiously when reporting a single value as a clinical ly important change BACKGROUND We conducted a double-blind , r and omized , placebo-controlled study to evaluate the efficacy of telithromycin in patients with acute exacerbations of asthma . METHODS A total of 278 adults with diagnosed asthma were enrolled within 24 hours after an acute exacerbation of asthma requiring short-term medical care . The patients were r and omly assigned to receive 10 days of oral treatment with telithromycin ( at a dose of 800 mg daily ) or placebo in addition to usual care . Primary efficacy end points were a change from baseline over the treatment period in symptoms ( as recorded by patients in a diary card ) and in the peak expiratory flow in the morning at home . The presence of Chlamydophila pneumoniae or Mycoplasma pneumoniae was ascertained by serologic analysis , polymerase chain reaction , and culture . RESULTS Of the two prespecified primary outcomes , only asthma symptoms showed a significantly greater reduction among patients receiving telithromycin than among those receiving placebo .  Mean ( + /-SD ) scores on a test of asthma symptoms ( on a 7-point scale , with 0 denoting no symptoms and 6 denoting severe symptoms ) were 3.0+/-1.4 at baseline and 1.7+/-1.1 at the end of treatment for the telithromycin group and 2.8+/-1.3 at baseline and 2.0+/-1.0 at the end of treatment for the placebo group . The mean decrease in symptom scores during the treatment period was 1.3 for telithromycin and 1.0 for placebo ( mean difference , -0.3 ; 95 percent confidence interval , -0.5 to -0.1 ; P=0.004 ) . There was no significant treatment effect on the other primary outcome measure , a change in morning peak expiratory flow . Nausea was more common among patients in the telithromycin group than in the placebo group ( P=0.01 ) . Although 61 percent of patients had evidence of infection with C. pneumoniae , M. pneumoniae , or both , there was no relationship between bacteriologic status and the response to asthma treatment . CONCLUSIONS This study provides evidence of the benefit of telithromycin in patients with acute exacerbations of asthma ; the mechanisms of benefit remain unclear . ( Clinical Trials.gov number , NCT00273520 . ) BACKGROUND Asthma exacerbations are major contributors to asthma morbidity and rather difficult to treat . There is inconclusive evidence that macrolide antibiotics may have an effect on asthma exacerbations through their antibacterial and /or anti-inflammatory properties . The aim of the study was to evaluate the efficacy of clarithromycin on medium-term asthma activity when given as an add-on therapy in children with acute asthma . METHODS This pilot , open-labeled , r and omized , prospect i ve study included 40 school-aged children , with intermittent or mild persistent asthma , presenting with an acute exacerbation . Children were r and omized to receive 15 mg/kg of clarithromycin for 3 wk , in addition to their regular ( GINA-guided ) exacerbation treatment . The microbial trigger of exacerbations was assessed by serology and PCR . Children were followed up with diary cards for 12 wk ; lung function was assessed at entry , 3 , and 12 wk after the exacerbation . RESULTS Children in the clarithromycin group had significantly more symptom-free days ( 78 ± 2 vs. 69 ± 6 days , p < 0.00001 ) and less total number of periods with loss of control ( 9 vs. 19 , respectively , p = 0.013 ) during the follow-up period , compared to controls . Moreover , treated children presented reduced duration of the index episode ( 5.0 ± 1 vs. 7.5 ± 1 days , p < 0.00001 ) . Lung function did not differ between groups . CONCLUSIONS When added to regular treatment , a 3-wk course of clarithromycin was associated with an increase in the number of symptom-free days , reductions in the number and severity of days with loss of control following index episode , and a decrease in the duration of the initial asthma exacerbation The value of antibiotics was assessed in a r and omised , double-blind study of amoxycillin and placebo in sixty adults admitted to hospital with acute exacerbations of asthma . 37 exacerbations were treated with amoxycillin and 34 were treated with placebo . Response to treatment was closely monitored but no significant difference in improvement was demonstrated between groups for length of hospital stay , time taken for 50 % improvement in symptoms , patient 's self assessment and respiratory function , and symptoms and respiratory function at time of discharge from hospital .  Antibiotics should not be given routinely to patients admitted to hospital with acute exacerbations of asthma Importance Guidelines recommend against antibiotic use to treat asthma attacks . A study with telithromycin reported benefit , but adverse reactions limit its use . Objective To determine whether azithromycin added to st and ard care for asthma attacks in adults results in clinical benefit . Design , Setting , and Participants The Azithromycin Against Placebo in Exacerbations of Asthma ( AZALEA ) r and omized , double-blind , placebo-controlled clinical trial , a United Kingdom-based multicenter study in adults requesting emergency care for acute asthma exacerbations , ran from September 2011 to April 2014 . Adults with a history of asthma for more than 6 months were recruited within 48 hours of presentation to medical care with an acute deterioration in asthma control requiring a course of oral and /or systemic corticosteroids . Interventions Azithromycin 500 mg daily or matched placebo for 3 days . Main Outcomes and Measures The primary outcome was diary card symptom score 10 days after r and omization , with a hypothesized treatment effect size of -0.3 . Secondary outcomes were diary card symptom score , quality -of-life question naires , and lung function changes , all between exacerbation and day 10 , and time to a 50 % reduction in symptom score . Results Of 4582 patients screened at 31 centers , 199 of a planned 380 were r and omized within 48 hours of presentation . The major reason for nonrecruitment was receipt of antibiotics ( 2044 [ 44.6 % ] screened patients ) . Median time from presentation to drug administration was 22 hours ( interquartile range , 14 - 28 hours ) . Exacerbation characteristics were well balanced across treatment arms and centers . The primary outcome asthma symptom scores were mean ( SD ) , 4.14 ( 1.38 ) at exacerbation and 2.09 ( 1.71 ) at 10 days for the azithromycin group and 4.18 ( 1.48 ) and 2.20 ( 1.51 ) for the placebo group , respectively . Using multilevel modeling , there was no significant difference in symptom scores between azithromycin and placebo at day 10 ( difference , -0.166 ; 95 % CI , -0.670 to 0.337 ) , nor on any day between exacerbation and day 10 . No significant between-group differences were observed in quality -of-life question naires or lung function between exacerbation and day 10 , or in time to 50 % reduction in symptom score . Conclusions and Relevance In this r and omized population , azithromycin treatment result ed in no statistically or clinical ly significant benefit . For each patient r and omized , more than 10 were excluded because they had already received antibiotics . Trial Registration clinical trials.gov Identifier : NCT01444469
BACKGROUND Asthma is a chronic respiratory condition that affects over 300 million adults and children worldwide .
It is characterised by wheeze , cough , chest tightness , and shortness of breath .
Symptoms typically are intermittent and may worsen over a short time , leading to an exacerbation .
Asthma exacerbations can be serious , leading to hospitalisation or even death in rare cases .
Exacerbations may be treated by increasing an individual 's usual medication and providing additional medication , such as oral steroids .
Although antibiotics are sometimes included in the treatment regimen , bacterial infections are thought to be responsible for only a minority of exacerbations , and current guidance states that antibiotics should be reserved for cases in which clear signs , symptoms , or laboratory test results are suggestive of bacterial infection .
OBJECTIVES To determine the efficacy and safety of antibiotics in the treatment of asthma exacerbations .