Cellular profiles of induced sputum in children with stable cystic fibrosis: comparison with BAL

Reinhardt, Nicole; Chen, C I U; Loppow, D; Schink, Tania; Kleinau, I; Jörres, RA; Wahn, Ulrich; Magnussen, H; Paul, K.

doi:10.1183/09031936.03.00043603

Cited by 26 publications

(22 citation statements)

References 21 publications

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“…Data from two published studies demonstrate reasonably good reproducibility of induced sputum cell counts and neutrophil percentages in clinically stable children (138) and adults (139) with CF. In addition, measurements of inflammatory mediators, including cytokines and proteases in CF sputum, are fairly reproducible (139,140).…”

Section: Reproducibilitymentioning

confidence: 90%

Sputum Biomarkers of Inflammation in Cystic Fibrosis Lung Disease

Sagel

Chmiel²,

Konstan³

2007

Proceedings of the American Thoracic Society

158

162

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Pulmonary biomarkers are being used more frequently to monitor disease activity and evaluate response to treatment in individuals with cystic fibrosis (CF). This article summarizes the current state of knowledge of biomarkers of inflammation relevant to CF lung disease, and the tools to measure inflammation, with specific emphasis on sputum. Sputum is a rich, noninvasive source of biomarkers of inflammation and infection. Sputum induction, through the inhalation of hypertonic saline, has expanded the possibilities for monitoring airway inflammation and infection, especially in individuals who do not routinely expectorate sputum. We critically examine the existing data supporting the validity of sputum biomarkers in CF, with an eye toward their application as surrogate endpoints or outcome measures in CF clinical trials. Further validation studies are needed regarding the variability of inflammatory biomarker measurements, and to evaluate how these biomarkers relate to disease severity, and to longitudinal changes in lung function and other clinical endpoints. We highlight the need to incorporate sputum collection, by induction if necessary, and measurement of sputum biomarkers into routine CF clinical care. In the future, pulmonary biomarkers will likely be useful in predicting disease progression, indicating the onset and resolution of a pulmonary exacerbation, and assessing response to current therapies or candidate therapeutics.

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Section: Reproducibilitymentioning

confidence: 90%

Sputum Biomarkers of Inflammation in Cystic Fibrosis Lung Disease

Sagel

Chmiel²,

Konstan³

2007

Proceedings of the American Thoracic Society

158

162

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“…At first glance, it may therefore be preferable to use BAL for the assessment of antiprotease treatment effects in CF patients. However in CF patients, elastase and neutrophils are more abundant in sputum compared with BAL [35,36]. Furthermore, it must be kept in mind that BAL reflects also the alveolar compartment and CF lung disease is primarily confined to the bronchial and bronchiolar compartment.…”

Section: Discussionmentioning

confidence: 99%

α₁-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients

Griese¹,

Latzin²,

Kappler³

et al. 2006

Eur Respir J

185

139

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The airways of cystic fibrosis (CF) patients are characterised by neutrophils that release high amounts of elastase overwhelming the local antiprotease shield. Inhalation of a 1 -antitrypsin (AAT) may restore the protease-antiprotease balance and attenuate airway inflammation in CF airways. The aims of the present study were: 1) to assess the best deposition region for inhaled AAT by two different inhalation strategies; and 2) to examine the effect of 4 weeks of AAT inhalation on lung function, protease-antiprotease balance and airway inflammation in CF patients.In a prospective, randomised study, 52 CF patients received a daily deposition by inhalation of 25 mg AAT for 4 weeks targeting their peripheral or bronchial compartment. The levels of elastase activity, AAT, pro-inflammatory cytokines, neutrophils, immunoglobulin G fragments and the numbers of Pseudomonas aeruginosa were assessed in induced sputum before and after the inhalation period.Inhalation of AAT increased AAT levels and decreased the levels of elastase activity, neutrophils, pro-inflammatory cytokines and the numbers of P. aeruginosa. However, it had no effect on lung function. No difference was found between the peripheral and bronchial inhalation mode.In conclusion, although no effect on lung function was observed, the clear reduction of airway inflammation after a 1 -antitrypsin treatment may precede pulmonary structural changes. The a 1 -antitrypsin deposition region may play a minor role for a 1 -antitrypsin inhalation in cystic fibrosis patients.

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“…The obtained BALF was filtered through two layers of sterile gauze. The first fraction of BALF was used because it contains higher percentages of neutrophils compared with the pooled fraction (28). The sample processing was performed immediately on ice.…”

Section: Bronchoalveolar Lavagementioning

confidence: 99%

Infiltrated Neutrophils Acquire Novel Chemokine Receptor Expression and Chemokine Responsiveness in Chronic Inflammatory Lung Diseases

Hartl

Krauss‐Etschmann

Koller

et al. 2008

The Journal of Immunology

208

203

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Various inflammatory diseases are characterized by tissue infiltration of neutrophils. Chemokines recruit and activate leukocytes, but neutrophils are traditionally known to be restricted in their chemokine receptor (CR) expression repertoire. Neutrophils undergo phenotypic and functional changes under inflammatory conditions, but the mechanisms regulating CR expression of infiltrated neutrophils at sites of chronic inflammation are poorly defined. Here we show that infiltrated neutrophils from patients with chronic inflammatory lung diseases and rheumatoid arthritis highly express CR on their surface that are absent or only marginally expressed on circulating neutrophils, i.e., CCR1, CCR2, CCR3, CCR5, CXCR3, and CXCR4, as measured by flow cytometry, immunohistochemistry, and confocal microscopy. The induction of CR surface expression on infiltrated neutrophils was functionally relevant, because receptor activation by chemokine ligands ex vivo modulated neutrophil effector functions such as respiratory burst activity and bacterial killing. In vitro studies with isolated neutrophils demonstrated that the surface expression of CR was differentially induced in a cytokine-mediated, protein synthesis-dependent manner (CCR1, CCR3), through Toll-like (CXCR3) or NOD2 (CCR5) receptor engagement, through neutrophil apoptosis (CCR5, CXCR4), and/or via mobilization of intracellular CD63+ granules (CXCR3). CR activation on infiltrated neutrophils may represent a key mechanism by which the local inflammatory microenvironment fine-tunes neutrophil effector functions in situ. Since the up-regulation of CR was exclusively found on infiltrated neutrophils at inflammatory sites in situ, the targeting of these G protein-coupled receptors may have the potential to site-specifically target neutrophilic inflammation.

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Cellular profiles of induced sputum in children with stable cystic fibrosis: comparison with BAL

Cited by 26 publications

References 21 publications

Sputum Biomarkers of Inflammation in Cystic Fibrosis Lung Disease

Sputum Biomarkers of Inflammation in Cystic Fibrosis Lung Disease

α₁-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients

Infiltrated Neutrophils Acquire Novel Chemokine Receptor Expression and Chemokine Responsiveness in Chronic Inflammatory Lung Diseases

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Cellular profiles of induced sputum in children with stable cystic fibrosis: comparison with BAL

Cited by 26 publications

References 21 publications

Sputum Biomarkers of Inflammation in Cystic Fibrosis Lung Disease

Sputum Biomarkers of Inflammation in Cystic Fibrosis Lung Disease

α1-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients

Infiltrated Neutrophils Acquire Novel Chemokine Receptor Expression and Chemokine Responsiveness in Chronic Inflammatory Lung Diseases

Contact Info

Product

Resources

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α₁-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients