Mannose-Binding Lectin Gene Polymorphism Contributes to Recurrence of Infective Exacerbation in Patients With COPD

Lin, Chii Lan; Siu, L. Kristopher; Lin, Jiunn Diann; Liu, Chien Ying; Chian, Chih-Feng; Lee, Chun Nin; Chang, Feng Yee

doi:10.1378/chest.10-0375

Cited by 35 publications

(37 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Takabatake and colleagues [44] reported that a single nucleotide polymorphism in the CCL-1 gene, encoding a leucocyte chemotactic factor, was predictive of the frequency and severity of exacerbations, while polymorphic variation in surfactant protein B has also been linked with exacerbation frequency [45]. Mannose-binding lectin (MBL) deficiency is associated with susceptibility to respiratory infections; a higher frequency of MBL gene polymorphisms was noted in patients with COPD who experience frequent exacerbations [46] and may also predict hospital admission for COPD [47]. In addition to these, an increased exacerbation frequency was found in patients whose sputum contained markers suggestive of increased microsatellite DNA instability, suggesting that those patients with a higher DNA mutation rate experience more frequent exacerbations [48].…”

Section: Genetic Predisposition Of Exacerbation Susceptibilitymentioning

confidence: 99%

Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease

Wedzicha

Brill

Allinson

et al. 2013

BMC Med

219

182

View full text Add to dashboard Cite

Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.

show abstract

Section: Genetic Predisposition Of Exacerbation Susceptibilitymentioning

confidence: 99%

Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease

Wedzicha

Brill

Allinson

et al. 2013

BMC Med

219

182

View full text Add to dashboard Cite

show abstract

“…4 In clinical studies, MBL deficiency is associated with a predisposition to developing infection 5 with high virulence and severity (as in the case of invasive pneumococcal disease), 6-8 particularly within the respiratory tract. [9][10][11][12][13][14][15][16][17] In CF-associated bronchiectasis, there is good evidence that MBL deficiency affects disease course and severity. 18 Although there is also evidence implicating MBL deficiency in the development of nCF-Br in the specific context of common variable immunodeficiency, 19,20 no previous study has sought to investigate a potential link between low MBL levels and disease severity in nCF-Br.…”

Section: Introductionmentioning

confidence: 99%

Low serum mannose-binding lectin level is not associated with disease severity in non-cystic fibrosis bronchiectasis

et al. 2012

View full text Add to dashboard Cite

Deficiency of mannose-binding lectin (MBL), a serum protein involved in killing and promoting phagocytosis of pathogens, is associated with respiratory infection and disease progression in a number of acute and chronic lung diseases, including cystic fibrosis (CF)- associated bronchiectasis. No such association has been studied in non-CF bronchiectasis (nCF-Br). One hundred and thirty-three adult patients with nCF-Br were studied. Serum MBL levels were measured and deficiency defined using two cut-off levels, i.e. MBL ≤100 ng/ml and ≤600 ng/ml. Parameters of severity included lung function impairment, annual exacerbation and hospital admission rates, breathlessness, and Pseudomonas aeruginosa and Haemophilus influenzae infection rates. The incidence of MBL deficiency using cut-off levels of 100 ng/ml and 600 ng/ml was 10% and 26% respectively, similar to rates seen in the general population. There was no significant difference in mean FEV(1)% predicted between MBL deficient and sufficient patients at both cut-off levels (≤100 ng/ml: 63.8% vs. 64.6%, P = 0.91; ≤ 600 ng/ml: 66.5% vs. 63.9%, P = 0.56). In addition, exacerbation/hospital admission rates, symptoms of breathlessness and isolation/colonisation rates with P. aeruginosa and H. influenzae were similar in both groups at both cut-off levels. In conclusion, MBL deficiency is not associated with markers of disease severity in patients with nCF-Br.

show abstract

“…29 However, studies assessing the association of low MBL concentrations with acute exacerbations of COPD (AECOPDs) report conflicting results. [30][31][32] Accordingly, we prospectively measured MBL concentrations in a large cohort of subjects with COPD who were at increased risk of experiencing acute exacerbations and followed them for one year while tracking the number of acute exacerbations that occurred. Our hypothesis was that subjects with COPD who had an increased risk of experiencing an AECOPD would have more frequent acute exacerbations during one year of follow-up if they were deficient in MBL than if they were not.…”

Section: Introductionmentioning

confidence: 99%

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

Albert¹,

Connett²,

Curtis³

et al. 2012

COPD

View full text Add to dashboard Cite

Background:Mannose-binding lectin is a collectin involved in host defense against infection. Whether mannose-binding lectin deficiency is associated with acute exacerbations of chronic obstructive pulmonary disease is debated.Methods:Participants in a study designed to determine if azithromycin taken daily for one year decreased acute exacerbations had serum mannose-binding lectin concentrations measured at the time of enrollment.Results:Samples were obtained from 1037 subjects (91%) in the trial. The prevalence of mannose-binding lectin deficiency ranged from 0.5% to 52.2%, depending on how deficiency was defined. No differences in the prevalence of deficiency were observed with respect to any demographic variable assessed, and no differences were observed in time to first exacerbation, rate of exacerbations, or percentage of subjects requiring hospitalization for exacerbations in those with deficiency versus those without, regardless of how deficiency was defined.Conclusion:In a large sample of subjects with chronic obstructive pulmonary disease selected for having an increased risk of experiencing an acute exacerbation of chronic obstructive pulmonary disease, only 1.9% had mannose-binding lectin concentrations below the normal range and we found no association between mannose-binding lectin concentrations and time to first acute exacerbation or frequency of acute exacerbations during one year of prospective follow-up.

show abstract

Mannose-Binding Lectin Gene Polymorphism Contributes to Recurrence of Infective Exacerbation in Patients With COPD

Cited by 35 publications

References 35 publications

Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease

Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease

Low serum mannose-binding lectin level is not associated with disease severity in non-cystic fibrosis bronchiectasis

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

Contact Info

Product

Resources

About