Mannose-binding lectin deficiency and acute exacerbations of chronic obstructive pulmonary disease

Yoon

Allergy Asthma Immunol Res

et al. 2017

Baker's asthma is the most prevalent occupational asthma, and IgE-mediated response is known as a major pathogenesis. However, recent studies have suggested the involvement of innate immune response because wheat flour contains bacterial endotoxins or lipopolysaccharides. To further understand a role of innate immune response in the development of work-related respiratory symptoms (WRS) in bakery workers, we investigated mannose-binding lectin (MBL), one of the initiating components of the complement cascade in a single cohort of bakery workers. A total of 373 bakery workers completed a questionnaire regarding WRS. The bakery workers were divided into 2 groups according to previous history of allergic rhinitis (AR)/bronchial asthma (BA): those with history of AR/BA (group I) and those without (group II). We measured serum MBL levels by using enzyme-linked immunosorbant assay and genotyped 4 single nucleotide polymorphisms of the MBL2 gene (226G>A in exon 1, -554G>C, -431A>C, and -225G>C in the promoter) by using TaqMan assays. Fifty-nine subjects (15.5%) were previously diagnosed with AR/BA, and 64 subjects (16.8%) complained of WRS. No significant differences were found in serum MBL levels between groups I and II. However, in group II subjects, but not in group I subjects, the serum MBL levels were significantly higher in bakery workers with WRS than in those without. In addition, the serum MBL levels were significantly different according to genetic polymorphisms of the MBL2 gene and its haplotypes. In conclusion, serum MBL, affected by genetic polymorphisms, may be associated with WRS in bakery workers with no previous history of AR/BA.

Section: Discussionmentioning

confidence: 71%

“…Samples were diluted at a ratio of 1:4,000 for the assay and measured in duplicate as previously reported 2332. A high serum MBL level was defined as one which was greater than the mean serum MBL level (675.5 ng/mL).…”

Section: Methodsmentioning

confidence: 99%

Association of MBL With Work-Related Respiratory Symptoms in Bakery Workers

Yoon

Allergy Asthma Immunol Res

et al. 2017

“…Previous studies on the impact of MBL deficiency in COPD are inconsistent; none have enrolled >300 patients without preselection for a subset of patients with COPD, that is, frequent exacerbators, 23 or had sufficient follow-up time to evaluate exacerbation frequency, whereas we analysed the electronic medical record data from 1796 patients with COPD with an average follow-up of 5.4 years. In the present study, MBL deficiency status was not found to have an effect on decline in FEV 1 , mortality or hospital admissions for cardiovascular events.…”

Section: Discussionmentioning

confidence: 99%

Genetic mannose binding lectin deficiency is associated with airway microbiota diversity and reduced exacerbation frequency in COPD

Dicker

Crichton

Cassidy

et al. 2017

Thorax

BackgroundIn cystic fibrosis and bronchiectasis, genetic mannose binding lectin (MBL) deficiency is associated with increased exacerbations and earlier mortality; associations in COPD are less clear. Preclinical data suggest MBL interferes with phagocytosis of Haemophilus influenzae, a key COPD pathogen. We investigated whether MBL deficiency impacted on clinical outcomes or microbiota composition in COPD.MethodsPatients with COPD (n=1796) underwent MBL genotyping; linkage to health records identified exacerbations, lung function decline and mortality. A nested subcohort of 141 patients, followed for up to 6 months, was studied to test if MBL deficiency was associated with altered sputum microbiota, through 16S rRNA PCR and sequencing, or airway inflammation during stable and exacerbated COPD.FindingsPatients with MBL deficiency with COPD were significantly less likely to have severe exacerbations (incidence rate ratio (IRR) 0.66, 95% CI 0.48 to 0.90, p=0.009), or to have moderate or severe exacerbations (IRR 0.77, 95% CI 0.60 to 0.99, p=0.047). MBL deficiency did not affect rate of FEV1 decline or mortality. In the subcohort, patients with MBL deficiency had a more diverse lung microbiota (p=0.008), and were less likely to be colonised with Haemophilus spp. There were lower levels of airway inflammation in patients with MBL deficiency.InterpretationPatients with MBL deficient genotype with COPD have a lower risk of exacerbations and a more diverse lung microbiota. This is the first study to identify a genetic association with the lung microbiota in COPD.

“…Accumulating evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD [60,61] . In this respect, most of the potential biomarkers included in our list are proteins involved in inflammation or the immune response such as CRP, IL-6, beta defensin 2, among many others [25][26][27]29,36,37,54,[62][63][64][65][66][67][68][69][70][71][72][73][74] . One of the main causes leading to COPD is chronic smoking which exposes the respiratory tract to reactive oxygen species, resulting in oxidative stress and injury (which in the last instance leads also to inflammation) [59,75] .…”

Section: Copd Protein Biomarkersmentioning

confidence: 99%

Prioritization of COPD protein biomarkers, based on a systematic study of the literature

Camacho¹,

Klont²,

Horvatovich³

et al. 2016

Adv Precis Med

Chronic Obstructive Pulmonary Disease (COPD) is a chronic lung disease mostly due to smoking and until now diagnosed by spirometry (post bronchodilator FEV 1 /FVC <70%). However, in spite of the usefulness of FEV 1 as diagnostic and prognostic tool, it has proven to be a weak indicator of future exacerbations, unable to predict lung function decline within COPD patients, as well as unable to identify the smokers "susceptible" to developing COPD at an early stage. Thus, there is an urgent need for biomarkers that address these questions and support clinical decision making in the diagnosis and treatment of (early) COPD. In this respect, considerable efforts have been devoted to identifying protein biomarkers that enable a better understanding of this complex disease and leading to better diagnostic and prognostic tools. However, in spite of the wide range of candidates that have been suggested as potentially useful COPD biomarkers, most remained at the level of the initial discovery, and only fibrinogen has been approved by the Food and Drug Administration (FDA) as predictor for all-cause mortality and COPD exacerbations. There is thus a need for future investigations of these biomarkers in large-scale and well characterized studies in order to prove their usefulness as surrogate endpoints. Based on this, the aim of the present review is to advance COPD biomarker development by providing a comprehensive overview of protein biomarker candidates which have been evaluated in clinical studies and prioritize them according to their potential of becoming valid, clinically useful COPD biomarkers.