Lung Function and Sputum Characteristics of Patients with Severe Asthma During an Induced Exacerbation by Double-Blind Steroid Withdrawal

Veen, J. C. C. M. In't; Smits, Hermelijn H.; Hiemstra, P. S.; Zwinderman, A. E.; Sterk, Peter J.; Bel, Elisabeth H.

doi:10.1164/ajrccm.160.1.9809104

Cited by 105 publications

(52 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These infections, even though originally defined of viral origin, often involve mixed bacterial co-infection and several types of bacterial infections have been associated with acute asthma exacerbations or chronic stable asthma [6,7]. Eosinophils have been suggested to play an important role in asthma exacerbations [8,9].…”

Section: Introductionmentioning

confidence: 99%

Bacterial DNA delays human eosinophil apoptosis

Ilmarinen¹,

Hasala²,

Sareila³

et al. 2009

Pulmonary Pharmacology & Therapeutics

View full text Add to dashboard Cite

To cite this version:Pinja Ilmarinen, Hannele Hasala, Outi Sareila, Eeva Moilanen, Hannu Kankaanranta. Bacterial DNA delays human eosinophil apoptosis. Pulmonary Pharmacology & Therapeutics, 2009, 22 (3), pp.167. <10.1016/j.pupt.2008.11.012>. Please cite this article as: Ilmarinen P, Hasala H, Sareila O, Moilanen E, Kankaanranta H. Bacterial DNA delays human eosinophil apoptosis, Pulmonary Pharmacology & Therapeutics (2008), doi: 10.1016/j.pupt.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ODNs had occasionally parallel but less profound effect on eosinophil apoptosis, which was not dependent on endosomal acidification. The anti-apoptotic effect of CpG AcceptedODNs was dependent on phosphatidylinositol 3-kinase (PI3K) and nuclear factor-κB (NF-κB) but not mitogen-activated protein kinases (MAPKs) as determined by inhibitor studies. Although our results suggest CpG-dependent involvement of TLR9 in the action of phosphorothioate-modified ODNs, we interestingly found that the antiapoptotic action of native bacterial DNA in eosinophils is not dependent on unmethylated CpG motifs. This suggests that bacterial DNA contains a currently unknown recognition structure lacking from vertebrate DNA. Bacterial DNA-mediated suppression of eosinophil apoptosis is a novel mechanism for exacerbation of eosinophilic lung inflammation associated with bacterial respiratory tract infection.

show abstract

Section: Introductionmentioning

confidence: 99%

Bacterial DNA delays human eosinophil apoptosis

Ilmarinen¹,

Hasala²,

Sareila³

et al. 2009

Pulmonary Pharmacology & Therapeutics

View full text Add to dashboard Cite

show abstract

“…Abnormalities in differential cell counts re-emphasize the occurrence of different types of inflammation and their different causes (table 2), Airway inflammation is not airway inflammation is not airway inflammation! An increase in sputum eosinophils is regarded as characteristic of asthma and can be induced by inhaled allergen [34,35] or chemical sensitizers [36,37] in sensitized subjects and by a reduction in steroid treatment in steroiddependent asthma [21,38,39]. Serial measurements during periods at work and periods away from work can be used in the investigation of occupational asthma ( fig.…”

Section: Types and Causes Of Inflammationmentioning

confidence: 99%

“…The intensity of the neutrophilia is indicated by the total cell count and is most pronounced in bronchial infection. Noneosinophilic (usually neutrophilic) exacerbations of asthma are described but their cause and incidence has not been systematically examined [39,54]. A likely cause is viral infection [55].…”

Section: Types and Causes Of Inflammationmentioning

confidence: 99%

“…5). In this situation, sputum eosinophilia should draw attention to possible noncompliance [65], a common allergen or occupational [40] cause, or inadequate steroid treatment [39]. Alternatively, there maybe no eosinophilia but a neutrophilia, raising the possibility of misdiagnosis, associated disease [80], or steroid-resistant asthma [81].…”

Section: How To Use Sputum Examination In Clinical Practicementioning

confidence: 99%

See 1 more Smart Citation

Induced sputum cell counts: their usefulness in clinical practice

et al. 2000

View full text Add to dashboard Cite

Airway inflammation is fundamental to the aetiology and persistence of asthma and other airway conditions. The presence and type of airway inflammation can be difficult to detect clinically, delaying the introduction of appropriate treatment. Induced sputum cell counts are a relatively noninvasive, safe and reliable method of identifying airway inflammation. They can accurately discriminate eosinophilic airway inflammation from noneosinophilic airway inflammation, and help guide therapy. Eosinophilic airway inflammation is steroid responsive whilst noneosinophilic (usually neutrophilic) inflammation generally is not. Macrophages containing haemosiderin can be useful in detecting left ventricular dysfunction and macrophages containing lipid are suggestive of oropharyngeal reflux with microaspiration, both of which can complicate or confuse assessment of airway disease. To date, studies using induced sputum are primarily observational. Management studies based on examination of induced sputum are now needed to validate the clinical utility of this test.

show abstract

“…In some studies, exacerbations have been induced by the deliberate withdrawal of ICSs [28,43]. While this model [38,43,44] allows treatment options to be investigated in a controlled fashion, the results of such studies cannot necessarily be extrapolated to spontaneous exacerbations in community patients, where the most common trigger in both adults and children is viral infection.…”

Section: Definition Of Exacerbationsmentioning

confidence: 99%

Pharmacological strategies for self-management of asthma exacerbations

Reddel

Barnes²

2006

European Respiratory Journal

View full text Add to dashboard Cite

Written action plans are effective within asthma self-management, but there are few guidelines about the specific medication adjustments which can be recommended for selftreatment of exacerbations.This review examines pharmacological strategies for self-management of asthma exacerbations in adults, including those for inhaled corticosteroid/long-acting b 2 -agonist (ICS/LABA) users.Oral corticosteroids are well-established in clinical practice and clinical trials for the treatment of severe exacerbations, including during combination therapy. Evidence supports 7-10 days treatment, with no need to taper except to reduce side-effects. Doubling the dose of ICS is not effective. Several studies have shown benefit from high-dose ICS (2,400-4,000 mg beclomethasone equivalent) for 1-2 weeks. This may be achieved by adding a high-dose ICS inhaler to maintenance ICS or ICS/LABA therapy. There is inconclusive evidence about acutely increasing the dose of maintenance budesonide/formoterol for exacerbations, and no studies of this approach with fluticasone/salmeterol. For patients taking maintenance budesonide/formoterol, use of the same medication as-needed reduces exacerbations. Short-acting b 2 -agonists are still effective in producing bronchodilation during combination therapy; however, a higher dose may be required.There is a need for further studies to clarify remaining issues about self-management of asthma exacerbations, particularly with regard to side-effects of treatment and patient acceptability.

show abstract

Lung Function and Sputum Characteristics of Patients with Severe Asthma During an Induced Exacerbation by Double-Blind Steroid Withdrawal

Cited by 105 publications

References 30 publications

Bacterial DNA delays human eosinophil apoptosis

Bacterial DNA delays human eosinophil apoptosis

Induced sputum cell counts: their usefulness in clinical practice

Pharmacological strategies for self-management of asthma exacerbations

Contact Info

Product

Resources

About