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Increased cytokine/chemokines in serum from asthmatic and non-asthmatic patients with viral respiratory infection.

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Increased cytokine/chemokines in serum from asthmatic and non-asthmatic patients with viral respiratory infection.

Influenza Other Respi Viruses. 2013 Aug 21;

Authors: Giuffrida MJ, Valero N, Mosquera J, Alvarez de Mon M, Chacín B, Espina LM, Gotera J, Bermudez J, Mavarez A

Abstract
BACKGROUND: Respiratory viral infections can induce different cytokine/chemokine profiles in lung tissues and have a significant influence on patients with asthma. There is little information about the systemic cytokine status in viral respiratory-infected asthmatic patients compared with non-asthmatic patients.
OBJECTIVES: The aim of this study was to determine changes in circulating cytokines (IL-1β, TNF-α, IL-4, IL-5) and chemokines (MCP1: monocyte chemoattractant protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in patients with an asthmatic versus a non-asthmatic background with respiratory syncytial virus, parainfluenza virus or adenovirus respiratory infection. In addition, human monocyte cultures were incubated with respiratory viruses to determine the cytokine/chemokine profiles.
PATIENTS/METHODS: Patients with asthmatic (n = 34) and non-asthmatic (n = 18) history and respiratory infections with respiratory syncytial virus, parainfluenza, and adenovirus were studied. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in blood and culture supernatants was determined by ELISA. Monocytes were isolated by Hystopaque gradient and cocultured with each of the above-mentioned viruses.
RESULTS: Similar increased cytokine concentrations were observed in asthmatic and non-asthmatic patients. However, higher concentrations of chemokines were observed in asthmatic patients. Virus-infected monocyte cultures showed similar cytokine/chemokine profiles to those observed in the patients.
CONCLUSIONS: Circulating cytokine profiles induced by acute viral lung infection were not related to asthmatic status, except for chemokines that were already increased in the asthmatic status. Monocytes could play an important role in the increased circulating concentration of cytokines found during respiratory viral infections.

PMID: 23962134 [PubMed - as supplied by publisher]

Efficacy and safety of high-dose ciclesonide for the treatment of severe asthma.

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Efficacy and safety of high-dose ciclesonide for the treatment of severe asthma.

Expert Rev Respir Med. 2013 Aug;7(4):339-48

Authors: Bateman ED

Abstract
Asthma severity is classified according to the level of treatment required to control symptoms. Inhaled corticosteroids are the recommended first-line therapy for the treatment of persistent asthma, and when asthma remains uncontrolled, one option is to increase the inhaled corticosteroids dose. However, there is a concomitant risk of increasing local and systemic adverse events, which may impact patient adherence and physician prescribing practices. Ciclesonide is delivered as a prodrug, has high peripheral lung deposition and high protein-binding capabilities, and is rapidly eliminated from the systemic circulation. This article reviews the use of high-dose ciclesonide in patients with severe asthma and considers whether the pharmacology of ciclesonide translates into it being an efficacious and well-tolerated option for patients requiring a step-up in their asthma treatment.

PMID: 23964625 [PubMed - in process]

Risk of invasive pneumococcal disease in children and adults with asthma: A systematic review.

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Risk of invasive pneumococcal disease in children and adults with asthma: A systematic review.

Vaccine. 2013 Aug 16;

Authors: Boikos C, Quach C

Abstract
BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommended the inclusion of asthma as a high-risk condition that should warrant pneumococcal vaccination, but the National Advisory Committee on Immunization (NACI) in Canada has not yet done so. We aimed to determine the risk of invasive pneumococcal disease (IPD) in patients with asthma.
METHODS: We searched Ovid Medline, EMBASE, Classic EMBASE, PubMEd and Cochrane for articles published between January 1990 and February 2013, using the MeSH terms pneumococcal infections/or invasive pneumococcal disease and asthma. Google Scholar was used to retrieve articles citing the seminal article by Talbot et al. Articles were included if they were population-based studies that evaluated the relationship between IPD and asthma. Two authors independently assessed all titles and abstracts. All potentially relevant articles were retrieved as full text and assessed for inclusion.
RESULTS: The combined searches yielded 376 articles, which were reviewed by title and abstract. At this stage, 330 articles were excluded; 40 articles were excluded at the full article review stage - leaving 6 articles. Two additional articles were found through Google Scholar. The evidence reviewed consistently showed a positive association between asthma and risk of IPD. However, the magnitude of this effect was heterogeneous with adjusted odds ratios ranging from 6.7 (95% CI 1.6-27.3) in adults >18 years to 1.7 (95% CI 0.99-3.0) in individuals aged 2-49 with low-risk asthma.
CONCLUSION: The positive association between asthma and risk of IPD supports the addition of asthma as a high-risk condition warranting pneumococcal vaccination. Data on vaccine effectiveness in this population is needed.

PMID: 23965221 [PubMed - as supplied by publisher]

Combined inhaled anticholinergics and short-acting beta2-agonists for initial treatment of acute asthma in children.

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There are several treatment options for managing acute asthma exacerbations (sustained worsening of symptoms that do not subside with regular treatment and require a change in management). Guidelines advocate the use of inhaled short acting beta2-agonists (SABAs) in children experiencing an asthma exacerbation. Anticholinergic agents, such as ipratropium bromide and atropine sulfate, have a slower onset of action and weaker bronchodilating effect, but may specifically relieve cholinergic bronchomotor tone and decrease mucosal edema and secretions. Therefore, the combination of inhaled anticholinergics with SABAs may yield enhanced and prolonged bronchodilation.

OBJECTIVES: To determine whether the addition of inhaled anticholinergics to SABAs provides clinical improvement and affects the incidence of adverse effects in children with acute asthma exacerbations.

SEARCH METHODS: We searched MEDLINE (1966 to April 2000), EMBASE (1980 to April 2000), CINAHL (1982 to April 2000) and reference lists of studies of previous versions of this review. We also contacted drug manufacturers and trialists. For the 2012 review update, we undertook an 'all years' search of the Cochrane Airways Group's register on the 18 April 2012.

SELECTION CRITERIA: Randomized parallel trials comparing the combination of inhaled anticholinergics and SABAs with SABAs alone in children (aged 18 months to 18 years) with an acute asthma exacerbation.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We used the GRADE rating system to assess the quality of evidence for our primary outcome (hospital admission).

MAIN RESULTS: Twenty trials met the review eligibility criteria, generated 24 study comparisons and comprised 2697 randomised children aged one to 18 years, presenting predominantly with moderate or severe exacerbations. Most studies involved both preschool-aged children and school-aged children; three studies also included a small proportion of infants less than 18 months of age. Nine trials (45%) were at a low risk of bias. Most trials used a fixed-dose protocol of three doses of 250 mcg or two doses of 500 mcg of nebulized ipratropium bromide in combination with a SABA over 30 to 90 minutes while three trials used a single dose and two used a flexible-dose protocol according to the need for SABA.The addition of an anticholinergic to a SABA significantly reduced the risk of hospital admission (risk ratio (RR) 0.73; 95% confidence interval (CI) 0.63 to 0.85; 15 studies, 2497 children, high-quality evidence). In the group receiving only SABAs, 23 out of 100 children with acute asthma were admitted to hospital compared with 17 (95% CI 15 to 20) out of 100 children treated with SABAs plus anticholinergics. This represents an overall number needed to treat for an additional beneficial outcome (NNTB) of 16 (95% CI 12 to 29).Trends towards a greater effect with increased treatment intensity and with increased asthma severity were observed, but did not reach statistical significance. There was no effect modification due to concomitant use of oral corticosteroids and the effect of age could not be explored. However, exclusion of the one trial that included infants (< 18 months) and contributed data to the main outcome, did not affect the results. Statistically significant group differences favoring anticholinergic use were observed for lung function, clinical score at 120 minutes, oxygen saturation at 60 minutes, and the need for repeat use of bronchodilators prior to discharge from the emergency department. No significant group difference was seen in relapse rates.Fewer children treated with anticholinergics plus SABA reported nausea and tremor compared with SABA alone; no significant group difference was observed for vomiting.

AUTHORS' CONCLUSIONS: Children with an asthma exacerbation experience a lower risk of admission to hospital if they are treated with the combination of inhaled SABAs plus anticholinergic versus SABA alone. They also experience a greater improvement in lung function and less risk of nausea and tremor. Within this group, the findings suggested, but did not prove, the possibility of an effect modification, where intensity of anticholinergic treatment and asthma severity, could be associated with greater benefit.Further research is required to identify the characteristics of children that may benefit from anticholinergic use (e.g. age and asthma severity including mild exacerbation and impending respiratory failure) and the treatment modalities (dose, intensity, and duration) associated with most benefit from anticholinergic use better.

Effects of two inhaled corticosteroid/long-acting beta-agonist combinations on small-airway dysfunction in mild asthmatics measured by impulse oscillometry.

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We previously showed that the long-acting beta agonist (LABA) salmeterol as inhalation powder or metered-dose inhaler improves lung-function parameters assessed by impulse oscillometry (IOS) in 2- to 5-year-old children with reversible-airway disease within 15 minutes.

OBJECTIVE: We studied 12- to 45-year-olds with mild persistent asthma in order to compare the onset and extent of peripheral airway effects following the first dose and after 4 weeks dosing with two inhaled corticosteroid (ICS)/LABA combinations: fluticasone propionate/salmeterol 115/21 and budesonide/formoterol 160/4.5.

METHODS: Thirty subjects with mild persistent asthma using only an as-needed short-acting beta-agonist (albuterol) who had at least a 40% change in integrated low-frequency reactance postalbuterol were selected and randomized to receive either fluticasone propionate/salmeterol or budesonide/formoterol (15 subjects each). We collected three to six IOS replicates at baseline, at 5, 20, 40, 60, 120, and 240 minutes postdose at randomization, and after 4 weeks of twice-daily dosing. Blinded investigators calculated IOS frequency-dependent resistance and reactance (R5-R20 and AX), indicative of small-airway dysfunction, and also estimated the peripheral airway resistance (Rp ) and peripheral airway compliance (Cp ), using a respiratory-impedance model.

RESULTS: At randomization visits, onset of action was detected as early as 5 minutes (t-test, P < 0.05) after fluticasone propionate/salmeterol by Cp , and within 5 minutes after budesonide/formoterol by R5-R20, AX, Rp , and Cp . However, after 4 weeks of dosing, only Rp was significantly different (from 60 to 120 minutes) after fluticasone propionate/salmeterol, while R5-R20, AX, Rp , and Cp were not significantly different within 240 minutes after budesonide/formoterol.

CONCLUSION: These two ICS/LABA combinations initially improved the peripheral airway function of 12- to 45-year-old asthmatics significantly in about 5 minutes or less, as measured by R5-R20, AX, Rp , and/or Cp . After regular dosing for 4 weeks, pre- to postdose differences in these parameters had diminished significantly due to improved predose status of peripheral airways. Single dosing with ICS/LABA combinations in mild persistent asthma improves small-airway function, and the effect is maintained over a 12-hour interval by regular use for 4 weeks.

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