Induced sputum: a window to lung pathology

Nicholas, Ben; Djukanović, Ratko

doi:10.1042/bst0370868

Cited by 57 publications

(48 citation statements)

References 45 publications

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“…15–20 min) appear to have similar success rates and feasibility to the longer inhalation times (30 min) [27]. Since saliva generally contains much lower levels of mucins [48], possible contamination with saliva may have contributed to the final results obtained. In spite of these limitations, the main results of our study were straightforward and significant.…”

Section: Discussionmentioning

confidence: 99%

Levels of Surfactant Proteins A and D and KL-6 Are Elevated in the Induced Sputum of Chronic Obstructive Pulmonary Disease Patients: A Sequential Sputum Analysis

et al. 2011

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Background: Recent clinical studies have suggested that serum surfactant protein (SP) A, SP-D and Krebs von den Lungen-6 (KL-6) are potential biomarkers for interstitial lung diseases. Serum levels of SP-A and SP-D have also been found to be elevated in chronic obstructive pulmonary disease (COPD), but their significance has not been evaluated or compared in induced sputum samples obtained directly from the airways. Objective: A sequential sputum analysis was conducted to assess the value of SP-A, SP-D and KL-6 levels in COPD. Methods: The study material consisted of induced sputum samples from 61 subjects, 28 with COPD and 33 with prolonged cough (cough lasting >3 weeks and normal spirometry). Sputum was collected in 3 fractions (3 periods of 5 min each). Sputum levels of these proteins were measured, and receiver operating characteristic curve analysis was carried out to evaluate the sensitivity, specificity and area under the curve (AUC) for each fraction. Results: The levels of SP-A, SP-D and KL-6 were higher in patients with COPD than in those with prolonged cough in each of the fractions. Sputum levels of these proteins correlated inversely with obstruction and positively with ageing, smoking history, sputum macrophages and eosinophils. Sputum fractionation had a relatively minor effect on the levels and AUC of these proteins. Conclusion: Sequential sputum analysis from 3 consecutive fractions indicated a significant difference in the levels of SP-A, SP-D and KL-6 between COPD and prolonged cough. However, sputum fractionation itself had a relatively minor effect on the levels of these proteins.

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Section: Discussionmentioning

confidence: 99%

Levels of Surfactant Proteins A and D and KL-6 Are Elevated in the Induced Sputum of Chronic Obstructive Pulmonary Disease Patients: A Sequential Sputum Analysis

et al. 2011

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“…They act by binding to 7-transmembrane G-protein coupled receptors on leukocytes. Signaling via these receptors leads to migration of the white cells into the area of damage and infection Marion Frankenberger,1,2 Christiane Eder, 1 Thomas PJ Hofer, 1,4 Irene Heimbeck, 1 Kerstin Skokann, 1,3 Gudrun Kaßner, 1,2 Norbert Weber, 5 Winfried Möller, 1,4 and Loems Ziegler-Heitbrock 1,3 to fight the microbes and clear the damaged tissue. Chemokines can be assigned to two major groups, that is, the CXC chemokines and the CC chemokines, depending on whether there is an additional amino acid between the two N-terminal cysteines or not.…”

Section: Introductionmentioning

confidence: 99%

“…Analysis of sputum is a noninvasive approach to understanding disease processes in inflammatory airway disease (1). Many studies have looked at cell-free sputum supernatants and have reported increased levels of cytokines, chemokines and proteases (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Chemokine Expression by Small Sputum Macrophages in COPD

Frankenberger

Eder

Hofer

et al. 2011

Mol Med

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Small sputum macrophages represent highly active cells that increase in the airways of patients with inflammatory diseases such as chronic obstructive pulmonary disease (COPD). It has been reported often that levels of cytokines, chemokines and proteases are increased in sputum supernatants of these patients. In COPD, the small sputum macrophages may contribute to these supernatant proteins and recruit additional cells via specific chemokine expression patterns. We therefore investigated the expression profile of chemokines in sputum macrophages obtained from COPD patients in comparison to cells from healthy donors and cells isolated after inhalation of lipopolysaccharide (LPS). We used the minimally invasive procedure of sputum induction and have purified macrophages with the RosetteSep technology. Using macrophage purification and flow cytometry we show that in COPD small sputum macrophages account for 85.9% ± 8.3% compared with 12.9% ± 7.1% of total macrophages in control donors. When looking at chemokine expression we found, for the small macrophages in COPD, increased transcript and protein levels for CCL2, CCL7, CCL13 and CCL22 with a more than 100-fold increase for CCL13 mRNA (P < 0.001). Looking at active smokers without COPD, there is a substantial increase of small macrophages to 60% ± 15% and, here, chemokine expression is increased as well. In a model of airway inflammation healthy volunteers inhaled 20 μg of lipopolysaccharide (LPS), which resulted in an increase of small sputum macrophages from 18% ± 19% to 64% ± 25%. The pattern of chemokine expression was, however, different with an upregulation for CCL2 and CCL7, while CCL13 was downregulated three-fold in the LPS-induced small macrophages. These data demonstrate that sputum macrophages in COPD show induction of a specific set of CCL chemokines, which is distinct from what can be induced by LPS.

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“…Sputum induction is a safe and reliable method of obtaining information about inflammatory cells and mediators in COPD [12]. However, it is a time consuming procedure and patients may find it unpleasant.…”

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confidence: 99%

Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD

Nijs²,

et al. 2011

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Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) is predictive for responses to inhaled steroids. We hypothesised that the inflammatory subtype in mild and moderate COPD can be assessed by exhaled breath metabolomics.Exhaled compounds were analysed using gas chromatography and mass spectrometry (GC-MS) and electronic nose (eNose) in 28 COPD patients (12/16 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I/II, respectively). Differential cell counts, eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were measured in induced sputum. Relationships between exhaled compounds, eNose breathprints and sputum inflammatory markers were analysed and receiver operating characteristic (ROC) curves were constructed.Exhaled compounds were highly associated with sputum cell counts (eight compounds with eosinophils, 17 with neutrophils; p,0.01). Only one compound (alkylated benzene) overlapped between eosinophilic and neutrophilic profiles. GC-MS and eNose breathprints were associated with markers of inflammatory activity in GOLD stage I (ECP: 19 compounds, p,0.01; eNose breathprint r50.84, p50.002) (MPO: four compounds, p,0.01; eNose r50.72, p50.008). ROC analysis for eNose showed high sensitivity and specificity for inflammatory activity in mild COPD (ECP: area under the curve (AUC) 1.00; MPO: AUC 0.96) but not for moderate COPD.Exhaled molecular profiles are closely associated with the type of inflammatory cell and their activation status in mild and moderate COPD. This suggests that breath analysis may be used for assessment and monitoring of airway inflammation in COPD.

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Induced sputum: a window to lung pathology

Cited by 57 publications

References 45 publications

Levels of Surfactant Proteins A and D and KL-6 Are Elevated in the Induced Sputum of Chronic Obstructive Pulmonary Disease Patients: A Sequential Sputum Analysis

Levels of Surfactant Proteins A and D and KL-6 Are Elevated in the Induced Sputum of Chronic Obstructive Pulmonary Disease Patients: A Sequential Sputum Analysis

Chemokine Expression by Small Sputum Macrophages in COPD

Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD

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