The Interrelationship of Sputum Inflammatory Markers in Patients with Chronic Bronchitis

Hill, Adam T.; Bayley, D L; Stockley, Robert A.

doi:10.1164/ajrccm.160.3.9901091

Cited by 211 publications

(148 citation statements)

References 25 publications

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“…Active neutrophil elastase was measured using a chromogenic substrate specific for human neutrophil elastase, n-methoxysuccinyl-L-alanyl-L-alanyl-prolyl-L-valyl-p-nitroanilide (Sigma), as described previously. 26 Both IL8 and neutrophil elastase have been previously validated for assessment in induced sputum. 27 SP-A concentration was determined by adapting a previously described method.…”

Section: Asthma Subtype Classificationmentioning

confidence: 99%

Innate immune activation in neutrophilic asthma and bronchiectasis

Simpson

Grissell

Douwes

et al. 2007

Thorax

295

288

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Background: The role of the innate immune system in the pathogenesis of asthma is unclear. Activation of innate immune receptors in response to bacterial lipopolysaccharide, viral infection and particulate matter triggers a pre-programmed inflammatory response, which involves interleukin (IL)8 and neutrophil influx. The inflammatory response in asthma is heterogeneous. Aim: To test the hypothesis that innate immune activation may be a relevant inflammatory mechanism in neutrophilic asthma where IL8 levels are increased. Methods: Induced sputum was obtained from non-smoking adults with asthma (n = 49), healthy controls (n = 13) and a positive reference group with bronchiectasis (n = 9). Subjects with asthma were classified into inflammatory subtypes using induced sputum cell counts. Sputum was examined for mRNA expression of the innate immune receptors toll-like receptor (TLR)2, TLR4 and CD14, and inflammatory cytokines. A separate sputum portion was dispersed and the supernatant assayed for surfactant protein A, IL8, soluble CD14 and endotoxin. Results: Expression of innate immune receptors was increased in subjects with bronchiectasis and neutrophilic asthma compared with other asthma subtypes and controls. Increased expression of the receptors TLR2, TLR4 and CD14, as well as the pro-inflammatory cytokines IL8 and IL1b, was observed. Subjects with neutrophilic asthma had higher airway levels of endotoxin than the other groups studied. Conclusion: There is evidence of activation of the innate immune system in asthma which results in the production of pro-inflammatory cytokines and may contribute to the pathogenesis of neutrophilic asthma.

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Section: Asthma Subtype Classificationmentioning

confidence: 99%

Innate immune activation in neutrophilic asthma and bronchiectasis

Simpson

Grissell

Douwes

et al. 2007

Thorax

295

288

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“…These assays and their characteristics have been described in detail elsewhere [24]. a 1 AT concentration in sputum sol phase was measured by ELISA relative to a commercially available serum standard (The Binding Site Ltd., Birmingham, UK) as described previously [16] and a 1 AT in serum was measured by radial immunodiffusion (The Binding Site Ltd.).…”

Section: Assay Analysismentioning

confidence: 99%

Airways inflammation in chronic bronchitis: the effects of smoking and alpha1-antitrypsin deficiency

Hill¹,

Bayley²,

Campbell³

et al. 2000

Eur Respir J

104

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Airways inflammation in chronic bronchitis is thought predominantly to be a direct consequence of neutrophil recruitment and release of elastase in response to factors such as cigarette smoke. The aims of this study were to assess the role of smoking and determine whether the serum elastase inhibitor α1‐antitrypsin (α1AT) influenced the process. Airways inflammation was compared between patients with chronic obstructive bronchitis with (n=39) and without (n=42) severe α1AT deficiency. The authors assessed the sputum concentration of the neutrophil chemoattractants interleukin‐8 (IL‐8) and leukotriene (LT)B4, myeloperoxidase (MPO) as a marker of neutrophil influx, neutrophil elastase activity and its natural inhibitors, α1AT and secretory leukoprotease inhibitor (SLPI). Finally serum α1AT was measured to determine the degree of protein leakage (sputum sol serum α1AT ratio). Compared to current smokers, the exsmokers had a lower concentration of the chemoattractant IL‐8 (p<0.05) and a lower MPO concentration, although this failed to reach conventional statistical significance (p=0.06). Patients with α1AT deficiency had greater inflammation in the larger airways with increased LTB4 (p<0.005), MPO (p<0.001), neutrophil elastase activity (p<0.01), protein leak (p<0.001), and were found to have a lower anti‐proteinase screen with both reduced sputum α1AT (p<0.001) and SLPI concentrations (p<0.05). The reduction in sputum interleukin‐8 levels in exsmokers may decrease neutrophil influx and thus explain the slower rate of neutrophil mediated progression of lung disease compared to subjects who continue to smoke. Patients with α1‐antitrypsin deficiency had greater inflammation suggesting that α1‐antitrypsin plays an important role in protecting the larger airways from the inflammatory effects of elastase activity and may explain their more rapid progression of disease.

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“…Moreover, sputum fluid-phase in COPD shows an increase in neutrophilic and eosinophilic granulocyte proteins such as Myeloperoxidase (MPO), Human Neutrophil Lipocalin (HNL), Neutrophil Elastase (NE) and Eosinophilic Cationic Protein (ECP), Eosinophil Peoxidase (EPO) and chemoattractants like Leukotriene B-4 (LTB-4), Growth Related Oncogen-a (GRO-a), Monocyte Chemotactic Protein-1 (MCP-1) and Granulocyte Macrophages-Colony Stimulating Factor (GM-CSF) [58][59][60].…”

Section: Inflammatory Mediatorsmentioning

confidence: 99%

“…Increased sputum concentration of proteins, including neutrophil Elastase and Metallopro- [59,[61][62][63].…”

Section: Inflammatory Mediatorsmentioning

confidence: 99%

Markers of airway inflammation in pulmonary diseases assessed by induced sputum

Dragonieri

Tongoussouva

Zanini

et al. 2016

Monaldi Arch Chest Dis

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During recent years there has been a growing interest in using non-invasive biomarkers to understand and monitor the airway inflammation in subjects with respiratory tract disorders. To date, the best validated and performing non-invasive biomarkers are measures of inflammation in induced sputum in both cellular and fluid phase, which can provide biological insights into the pathogenesis of respiratory diseases such as asthma and chronic obstructive pulmonary disease. The purpose of this review is to examine the principal literature on the different markers of inflammation in pulmonary diseases assessed by induced sputum analysis in either cellular or fluid phase.

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The Interrelationship of Sputum Inflammatory Markers in Patients with Chronic Bronchitis

Cited by 211 publications

References 25 publications

Innate immune activation in neutrophilic asthma and bronchiectasis

Innate immune activation in neutrophilic asthma and bronchiectasis

Airways inflammation in chronic bronchitis: the effects of smoking and alpha1-antitrypsin deficiency

Markers of airway inflammation in pulmonary diseases assessed by induced sputum

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