Increased serum SP-D in identification of high-risk smokers at high risk of COPD

Author(s):  
Christine Dalgård ◽  
Fang Wang ◽  
Ingrid Louise Titlestad ◽  
Kirsten Ohm Kyvik ◽  
Jørgen Vestbo ◽  
...  

Pulmonary surfactant protein D (SP-D) is an important component of the pulmonary innate immune system with the ability to dampen cigarette smoke-induced lung inflammation. However, cigarette smoking mediates translocation of SP-D from the lung to the blood, and serum SP-D (sSP-D) has therefore previously been suggested as marker for smoke-induced lung injury. In support of this notion, associations between high sSP-D and low lung function measurements have previously been demonstrated in smokers and in COPD. The present investigations employ a 12-year longitudinal Danish twin study to test the hypothesis that baseline sSP-D variation has the capacity to identify smokers with normal baseline lung function who are in high risk of significant future smoke-induced lung function decline. We find that sSP-D is significantly increased in those with normal lung function at baseline that develop lung function decline during follow up compared to those who stay lung healthy. Moreover, we demonstrate that it is the smoke-induced baseline sSP-D level, and not the constitutional level, which has capacity as biomarker, and which is linearly increased with the decline in lung function during follow up. In conclusion, we here present first observation of increased sSP-D for identification of high-risk smokers.

2016 ◽  
Vol 10 (1) ◽  
pp. 70-78 ◽  
Author(s):  
Bruno Sposato

Background: Asthma may show an accelerated lung function decline. Asthmatics, although having FEV1 and FEV1/VC (and z-scores) higher than the lower limit of normality, may show a significant FEV1 decline when compared to previous measurements. We assessed how many asymptomatic long-standing asthmatics (LSA) with normal lung function showed a significant FEV1 decline when an older FEV1 was taken as reference point. Methods: 46 well-controlled LSA (age: 48.8±12.1; 23 females) with normal FEV1 and FEV1/VC according to GLI2012 references (FEV1: 94.8±10.1%, z-score:-0.38±0.79; FEV1/VC: 79.3±5.2, z-score:-0.15±0.77) were selected. We considered FEV1 decline, calculated by comparing the latest value to one at least five years older or to the highest predicted value measured at 21 years for females and 23 for males. A FEV1 decline >15% or 30 ml/years was regarded as pathological. Results: When comparing the latest FEV1 to an at least 5-year-older one (mean 8.1±1.4 years between 2 measurements), 14 subjects (30.4%) showed a FEV1 decline <5% (mean: -2.2±2.6%), 19 (41.3%) had a FEV1 5-15% change (mean: -9.2±2.5%) and 13 (28.3%) a FEV1 decrease>15% (mean: -18.3±2.4). Subjects with a FEV1 decline>30 ml/year were 28 (60.8%). When using the highest predicted FEV1 as reference point and declines were corrected by subtracting the physiological decrease, 6 (13%) patients showed a FEV1 decline higher than 15%, whereas asthmatics with a FEV1 loss>30 ml/year were 17 (37%). Conclusion: FEV1 decline calculation may show how severe asthma actually is, avoiding a bronchial obstruction underestimation and a possible under-treatment in lots of apparent “well-controlled” LSA with GLI2012-normal-range lung function values.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ulrika Lindberg ◽  
Malin Carlsson ◽  
Claes-Göran Löfdahl ◽  
Mårten Segelmark

Introduction. Anti-neutrophil cytoplasmic antibodies specific for bactericidal/permeability-increasing protein (BPI-ANCA) are frequent in CF patients and mainly develop in response to infection withPseudomonas aeruginosa. It is not known to what extent BPI-ANCA correlates to prognosis.Objectives. To evaluate the prognostic value of IgA-BPI-ANCA, measured at the beginning of the study, for transplantation-free survival.Methods. A cohort of 46 adult, nontransplanted CF patients was generated, 1995–1998, and characterized using Leeds criteria, lung function, and IgA-BPI-ANCA levels measured by ELISA. The cohort was followed until December 2009, using the combined endpoint of death or lung transplantation.Results. Lung function and IgA-BPI-ANCA, but not Leeds criteria, were significantly associated with adverse outcome. No patient with normal lung function at baseline reached endpoint. Within 10 years 8/11 with high BPI-ANCA reached an endpoint compared to 3/17 ANCA-negative patients. A similar result was seen within the Leeds I group where 7 out of 9 BPI-ANCA-positive patients reached endpoint, compared to none of the 5 patients without BPI-ANCA.Conclusions. IgA-BPI-ANCA is associated with adverse outcome amongPseudomonas aeruginosainfected CF patients, suggesting that BPI-ANCA is a biomarker of an unfavourable host-pathogen interaction.


2017 ◽  
Vol 50 (5) ◽  
pp. 1700657 ◽  
Author(s):  
Ma'en Obeidat ◽  
Xuan Li ◽  
Stephen Burgess ◽  
Guohai Zhou ◽  
Nick Fishbane ◽  
...  

Surfactant protein D (SP-D) is produced primarily in the lung and is involved in regulating pulmonary surfactants, lipid homeostasis and innate immunity. Circulating SP-D levels in blood are associated with chronic obstructive pulmonary disease (COPD), although causality remains elusive.In 4061 subjects with COPD, we identified genetic variants associated with serum SP-D levels. We then determined whether these variants affected lung tissue gene expression in 1037 individuals. A Mendelian randomisation framework was then applied, whereby serum SP-D-associated variants were tested for association with COPD risk in 11 157 cases and 36 699 controls and with 11 years decline of lung function in the 4061 individuals.Three regions on chromosomes 6 (human leukocyte antigen region), 10 (SFTPDgene) and 16 (ATP2C2gene) were associated with serum SP-D levels at genome-wide significance. In Mendelian randomisation analyses, variants associated with increased serum SP-D levels decreased the risk of COPD (estimate −0.19, p=6.46×10−03) and slowed the lung function decline (estimate=0.0038, p=7.68×10−3).Leveraging genetic variation effect on protein, lung gene expression and disease phenotypes provided novel insights into SP-D biology and established a causal link between increased SP-D levels and protection against COPD risk and progression. SP-D represents a very promising biomarker and therapeutic target for COPD.


Author(s):  
Sun-Wung Hsieh ◽  
Da-Wei Wu ◽  
Chih-Wen Wang ◽  
Szu-Chia Chen ◽  
Chih-Hsing Hung ◽  
...  

Previous studies have reported an association between the impairment of cognitive performance and lung diseases. However, whether obstructive or restrictive lung diseases have an impact on cognitive function is still inconclusive. We aimed to investigate the association between cognitive function and obstructive or restrictive lung diseases in Taiwanese adults using the Mini-Mental State Examination (MMSE). In this study, we used data from the Taiwan Biobank. Cognitive function was evaluated using the MMSE. Spirometry measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained to assess lung function. Participants were classified into three groups according to lung function, namely, normal, restrictive, and obstructive lung function. In total, 683 patients enrolled, of whom 357 participants had normal lung function (52.3%), 95 had restrictive lung function (13.9%), and 231 had obstructive lung function (33.8%). Compared to the normal lung function group, the obstructive lung function group was associated with a higher percentage of cognitive impairment (MMSE < 24). In multivariable analysis, a low MMSE score was significantly associated with low FVC, low FEV1, and low FEV1/FVC. Furthermore, a low MMSE score was significantly associated with low FEV1 in the participants with FEV1/FVC < 70%, whereas MMSE was not significantly associated with FVC in the participants with FEV1/FVC ≥ 70%. Our results showed that a low MMSE score was associated with low FEV1, low FVC and low FEV1/FVC. Furthermore, a low MMSE score was associated with obstructive lung diseases but not with restrictive lung diseases.


2019 ◽  
Vol 54 (5) ◽  
pp. 610-619 ◽  
Author(s):  
Azza A. Tantawy ◽  
Amira A. Adly ◽  
Fatma S. E. Ebeid ◽  
Eman A. Ismail ◽  
Mahitab M. Hussein ◽  
...  

1997 ◽  
Vol 272 (3) ◽  
pp. L479-L485 ◽  
Author(s):  
M. Ikegami ◽  
T. R. Korfhagen ◽  
M. D. Bruno ◽  
J. A. Whitsett ◽  
A. H. Jobe

In the present study we asked if surfactant metabolism was altered in surfactant protein (SP) A-deficient mice in vivo. Although previous studies in vitro demonstrated that SP-A modulates surfactant secretion and reuptake by type II cells, mice made SP-A deficient by homologous recombination grow and reproduce normally and have normal lung function. Alveolar and lung tissue saturated phophatidylcholine (Sat PC) pools were 50 and 26% larger, respectively, in SP-A(-/-) mice than in SP-A(+/+) mice. Radiolabeled choline and palmitate incorporation into lung Sat PC was similar both in vivo and for lung tissue slices in vitro from SP-A(+/+) and SP-A(-/-) mice. Percent secretion of radiolabeled Sat PC was unchanged from 3 to 15 h, although SP-A(-/-) mice retained more labeled Sat PC in the alveolar lavages at 48 h (consistent with the increased surfactant pool sizes). Clearance of radiolabeled dipalmitoylphosphatidylcholine and SP-B from the air spaces after intratracheal injection was similar in SP-A(-/-) and SP-A(+/+) mice. Lack of SP-A had minimal effects on the overall metabolism of Sat PC or SP-B in mice.


2020 ◽  
Author(s):  
Songming Zhuo ◽  
Hong Zhuang ◽  
Na Li ◽  
Sida Chen ◽  
Wugen Zhan ◽  
...  

Abstract Background: This study aimed to shed light on the correlation between the amounts of CD8+ T cells and autophagy level in COPD. Results: The objects (n = 90) were divided into three groups: COPD group (patients in the stable phase; n = 30), SN group (healthy control of smoking with normal lung function group; n = 30), and NSN groups (healthy control of non-smoking with normal lung function group; n = 30). The amounts of CD8+ (32.33 ± 4.23%), CD8+ effector (25.63 ± 8.57%) and CD8+memory (11.94 ± 5.77%) T cell in the COPD group were significantly higher those in the other two groups, while the apoptotic rate was lower in the COPD group (P < 0.05). Significant linear correlations were found of P62/GAPDH (‰) with CD8+, CD8+effector, and CD8+ memory- T cell amounts (P<0.001). Conclusions: Autophagy level is positively and linearly associated with the amounts of CD8+ T cells, suggesting that cell autophagy might be involved in COPD pathogenesis.


2020 ◽  
Vol 3 (1) ◽  
pp. 2-8
Author(s):  
Robert A. Wise

Asthma and COPD are easily recognizable clinical entities in their characteristic presentations. Asthma is an early-onset disorder characterized by Type 2, eosinophil-predominant, inflammation of the airways and is associated with atopy. COPD presents in middle age and is characterized by neutrophilic inflammation of the airways and is associated with cigarette smoking or biomass fuel exposure. Between exacerbations, asthma typically has normal lung function whereas COPD has incompletely reversible lung function. Approximately one in five patients with either of these disorders will show some features of both COPD and Asthma. This overlap is far more common than can be accounted for by chance concurrence of two common diseases. There are likely genetic and environmental susceptibilities to both disorders, but there is no single pathobiological mechanism that identifies all such overlap patients. Most likely there are numerous predispositions that lead to Asthma-COPD overlap that may be grounded in early childhood or even pre-natal events. Thus, Asthma-COPD overlap is best considered a family of diseases with overlapping clinical manifestations. The future elucidation of these different pathways to Asthma-COPD overlap, in conjunction with highly targeted therapies will aid clinicians in treating these patients.


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