Surfactant protein levels in bronchoalveolar lavage after segmental allergen challenge in patients with asthma

Erpenbeck, Veit J.; Schmidt, Reinhold E.; Günther, Andreas; Krug, Norbert; Hohlfeld, Jens M.

doi:10.1111/j.1398-9995.2006.01062.x

Cited by 52 publications

(58 citation statements)

References 36 publications

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“…We found no consistent association between SP-B genotypes and any of the lung diseases we examined, except for asthma. As in previous reports on SP-C [26,27], a protein related to SP-B, we did find an association between SP-B rs3024791 rare versus common homozygosity and asthma. We could not confirm this result when analysing other SP-B genotypes, and further studies will be needed to conclusively determine whether the SP-B rs3024791 AA genotype is associated with increased asthma risk.…”

Section: Discussionsupporting

confidence: 72%

Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals

Bækvad-Hansen¹,

Nordestgaard²,

Dahl³

2010

Eur Respir J

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The surfactant protein (SP)-B gene may influence chronic obstructive pulmonary disease (COPD) and, thus, personalised medicine. We tested whether functional polymorphisms in SP-B (rs1130866 (1580T.C), rs2077079 (-18A.C) and rs3024791 (-384G.A)) associate with reduced lung function and risk of COPD in the general population.We genotyped 10,231 individuals from the general adult Danish population, and recorded spirometry and hospital admissions due to COPD. Because we previously found an association between the rare SP-B 121ins2 mutation and COPD among smokers, we stratified the analyses for smoking status.None of the individual SP-B genotypes or genotype combinations were associated with reduced forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % pred and FEV1/ FVC overall or among smokers (p50.25-0.99). The odds ratio for spirometrically defined COPD did not differ from 1.0 for any of the SP-B genotypes or genotype combinations overall or among smokers (p50.17-0.78). Similar results were obtained for hospitalisation due to COPD (p50.07-0.93); we could exclude overall hazard ratios for heterozygotes of 1.18-1.21 and for homozygotes of 1.25-1.57 or larger for all three polymorphisms.In conclusion, the functional rs1130866, rs2077079 and rs3024791 polymorphisms in the SP-B gene are not associated with reduced lung function or risk of COPD, making it unlikely that these variants will be useful in personalised medicine.

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Section: Discussionsupporting

confidence: 72%

Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals

Bækvad-Hansen¹,

Nordestgaard²,

Dahl³

2010

Eur Respir J

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“…Because SP-D function has been shown to be regulated by NO-mediated post-translational modifications, we hypothesized that acute allergic inflammation would alter SP-D structure and function. Therefore, we examined the effect of segmental challenge with antigen or endotoxin in subjects with mild allergic asthma (22)(23)(24). Here we show that acute segmental allergen challenge alone, or in combination with LPS, induces changes in SP-D multimeric structure in vivo that are associated with the loss of the ability of SP-D to inhibit eosinophil chemotaxis.…”

Section: What This Study Adds To the Fieldmentioning

confidence: 99%

Segmental Allergen Challenge Alters Multimeric Structure and Function of Surfactant Protein D in Humans

Atochina‐Vasserman¹,

Winkler²,

Abramova³

et al. 2011

Am J Respir Crit Care Med

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Rationale: Surfactant protein D (SP-D), a 43-kD collectin, is synthesized and secreted by airway epithelia as a dodecamer formed by assembly of four trimeric subunits. We have previously shown that the quaternary structure of SP-D can be altered during inflammatory lung injury through its modification by S-nitrosylation, which in turn alters its functional behavior producing a proinflammatory response in effector cells. Objectives: We hypothesized that alterations in structure and function of SP-D may occur in humans with acute allergic inflammation. Methods: Bronchoalveolar lavage (BAL) fluid was collected from 15 nonsmoking patients with mild intermittent allergic asthma before and 24 hours after segmental provocation with saline, allergen, LPS, and mixtures of allergen and LPS. Structural modifications of SP-D were analyzed by native and sodium dodecyl sulfate gel electrophoresis. Measurements and Main Results: The multimeric structure of native SP-D was found to be disrupted after provocation with allergen or a mixture of allergen and LPS. Interestingly, under reducing conditions, sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that 7 of 15 patients with asthma developed an abnormal cross-linked SP-D band after segmental challenge with either allergen or a mixture of allergen with LPS but not LPS alone. Importantly, patients with asthma with cross-linked SP-D demonstrated significantly higher levels of BAL eosinophils, nitrogen oxides, IL-4, IL-5, IL-13, and S-nitrosothiol-SP-D compared with patients without cross-linked SP-D. Conclusions: We conclude that segmental allergen challenge results in changes of SP-D multimeric structure and that these modifications are associated with an altered local inflammatory response in the distal airways.

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“…Wallaert et al [31] reported that asthmatic patients exhibited T-cell and degranulated mast cell infiltration and increased basement membrane thickness in the minor salivary glands and bronchial mucosa, suggesting that activated T cells may elicit airway-like inflammation in the salivary glands. Allergen challenge increased SP-D levels in BALF, which correlated with the degree of allergic inflammation in asthmatic lungs [32]. Animal studies in transgenic mice have shown that IL-4 and IL-13 increase SP-D expression [33].…”

Section: Salivary Sp-d Levels Correlate With R5-r20 In Asthmatic Chilmentioning

confidence: 99%

The Biomarker Salivary SP-D May Indicate Small Airway Inflammation and Asthma Exacerbation

Okazaki¹,

Murai²,

Kidoguchi³

et al. 2017

J Investig Allergol Clin Immunol

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Background: Noninvasive and child-friendly biomarkers are important tools for understanding the various phenotypes of childhood asthma. Objective: The aim of this study was to examine the usefulness of salivary surfactant protein (SP) D in assessing the pathophysiology of childhood asthma. Methods: We measured salivary concentrations of SP-D and forced oscillation technique (FOT) indexes in 19 healthy controls and 21 asthmatic children. Regression equations for the predictive values of FOT indexes were generated from healthy controls. We analyzed the correlations between salivary SP-D concentration and percentages of the predictive values of FOT indexes, as well as the severity of exacerbation. Results: We found that salivary SP-D levels were higher in asthmatic children than in healthy controls. In the asthmatic children, salivary SP-D levels correlated with the percentages of predicted differences in resistance between 5 Hz and 20 Hz (%R5-R20), which represented the resistance of peripheral airways, and with the severity of asthma exacerbation. Conclusion: Salivary SP-D may reflect asthmatic inflammation in peripheral small airways and may be a useful marker for monitoring the degree of exacerbation in childhood asthma.

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Surfactant protein levels in bronchoalveolar lavage after segmental allergen challenge in patients with asthma

Abstract: This study demonstrates significant alterations of all SPs in BAL fluid after allergen challenge of which SP-C was most closely related to surfactant dysfunction and the degree of the allergic inflammation.

Cited by 52 publications

References 36 publications

Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals

Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals

Segmental Allergen Challenge Alters Multimeric Structure and Function of Surfactant Protein D in Humans

The Biomarker Salivary SP-D May Indicate Small Airway Inflammation and Asthma Exacerbation

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