Sputum dipalmitoylphosphatidylcholine level as a novel airway inflammatory marker in asthmatic children

Shaheen, Malak; Mahmoud, Mohamed; Aziz, Manal M. Abdel; Morsy, Hamam Ibrahim El; Khalik, Karima Ahmed Abdel

doi:10.1111/j.1752-699x.2009.00127.x

Cited by 8 publications

(7 citation statements)

References 23 publications

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“…WRIGHT et al [21] observed that the proportion of PC32:0 was decreased in sputum, but not in BAL in patients with asthma, while CHANG et al [22] found that PC32:0 correlated with eosinophilic cationic protein in sputum of children with asthma. It has also been observed that children with asthma have higher levels of PC32:0 in sputum compared with control subjects [23]. In atopic asthma, experimental antigen exposure has been shown to induce a reduction in PG in large surfactant aggregates collected from BAL [24].…”

Section: Discussionmentioning

confidence: 89%

TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls

Almstrand

Josefson²,

Bredberg³

et al. 2011

Eur Respir J

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Particles in exhaled air (PEx) may reflect the composition of respiratory tract lining fluid (RTLF); thus, there is a need to assess their potential as sources of biomarkers for respiratory diseases. In the present study, we compared PEx from patients with asthma and controls using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) and multivariate analysis.Particles were collected using an instrument developed in-house. 15 nonsmoking subjects with physician-diagnosed asthma and 11 nonsmoking healthy controls performed 10 consecutive forced exhalations into the instrument. Particle concentrations were recorded and samples of particles collected on silicon plates were analysed by TOF-SIMS.Subjects with asthma exhaled significantly lower numbers of particles than controls (p50.03) and the ratio of unsaturated to saturated phospholipids was significantly lower in samples from subjects with asthma (0.25 versus 0.35; p50.036). Orthogonal partial least squares-discriminant analysis models showed good separation between both positive and negative spectra. Molecular ions from phosphatidylcholine and phosphatidylglycerol, and protein fragments were found to discriminate the groups.We conclude that analysis of PEx is a promising method to examine the composition of RTLF. In the present explorative study, we could discriminate between subjects with asthma and healthy controls based on TOF-SIMS spectra from PEx.

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Section: Discussionmentioning

confidence: 89%

TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls

Almstrand

Josefson²,

Bredberg³

et al. 2011

Eur Respir J

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“…However, FVC has previously been noted to negatively correlate with outdoor and indoor environmental exposures in children [ 44 – 47 ] and adults [ 48 ]. FVC in children has also been negatively correlated with various biomarkers including airway macrophage carbon content [ 45 ], exhaled breath malondialdehyde [ 46 ] and sputum dipalmitoylphosphatidylcholine [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Influence of viral infection on the relationships between airway cytokines and lung function in asthmatic children

et al. 2018

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BackgroundFew longitudinal studies examine inflammation and lung function in asthma. We sought to determine the cytokines that reduce airflow, and the influence of respiratory viral infections on these relationships.MethodsChildren underwent home collections of nasal lavage during scheduled surveillance periods and self-reported respiratory illnesses. We studied 53 children for one year, analyzing 392 surveillance samples and 203 samples from 85 respiratory illnesses. Generalized estimated equations were used to evaluate associations between nasal lavage biomarkers (7 mRNAs, 10 proteins), lung function and viral infection.ResultsAs anticipated, viral infection was associated with increased cytokines and reduced FVC and FEV1. However, we found frequent and strong interactions between biomarkers and virus on lung function. For example, in the absence of viral infection, CXCL10 mRNA, MDA5 mRNA, CXCL10, IL-4, IL-13, CCL4, CCL5, CCL20 and CCL24 were negatively associated with FVC. In contrast, during infection, the opposite relationship was frequently found, with IL-4, IL-13, CCL5, CCL20 and CCL24 levels associated with less severe reductions in both FVC and FEV1.ConclusionsIn asthmatic children, airflow obstruction is driven by specific pro-inflammatory cytokines. In the absence of viral infection, higher cytokine levels are associated with decreasing lung function. However, with infection, there is a reversal in this relationship, with cytokine abundance associated with reduced lung function decline. While nasal samples may not reflect lower airway responses, these data suggest that some aspects of the inflammatory response may be protective against viral infection. This study may have ramifications for the treatment of viral-induced asthma exacerbations.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0922-9) contains supplementary material, which is available to authorized users.

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“…Neither bronchoalveolar lavage (BAL) nor induced sputum appears to be optimal to determine their concentrations in ELF. Induced sputum is performed only in specialized centers and successful only in 30–40% of the cases with particularly low success rates in healthy individuals that produce little sputum [76]. DPPC levels measured in induced sputum were 49.3 ± 20.1 µg/mL in healthy children.…”

Section: Particle Action In the Deep Lungmentioning

confidence: 99%

“…DPPC levels measured in induced sputum were 49.3 ± 20.1 µg/mL in healthy children. As DPPC represents ~50% of total phospholipids, the concentration of phospholipids would be 0.1 mg/mL [76]. BAL has repeatedly been used for qualitative and quantitative measurement of protein and lipid levels of the ELF.…”

Section: Particle Action In the Deep Lungmentioning

confidence: 99%

Biological Obstacles for Identifying In Vitro-In Vivo Correlations of Orally Inhaled Formulations

Frőhlich

2019

Pharmaceutics

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Oral inhalation of drugs is the classic therapy of obstructive lung diseases. In contrast to the oral route, the link between in vitro and in vivo findings is less well defined and predictive models and parameters for in vitro-in vivo correlations are missing. Frequently used in vitro models and problems in obtaining in vivo values to establish such models and to identify the action of formulations in vivo are discussed. It may be concluded that major obstacles to link in vitro parameters on in vivo action include lack of treatment adherence and incorrect use of inhalers by patients, variation in inhaler performance, changes by humidity, uncertainties about lung deposition, and difficulties to measure drug levels in epithelial lining fluid and tissue. Physiologically more relevant in vitro models, improvement in inhaler performance, and better techniques for in vivo measurements may help to better understand importance and interactions between individual in vitro parameters in pulmonary delivery.

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Sputum dipalmitoylphosphatidylcholine level as a novel airway inflammatory marker in asthmatic children

Cited by 8 publications

References 23 publications

TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls

TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls

Influence of viral infection on the relationships between airway cytokines and lung function in asthmatic children

Biological Obstacles for Identifying In Vitro-In Vivo Correlations of Orally Inhaled Formulations

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