Mannose-binding lectin 2 gene polymorphism and lung damage in primary ciliary dyskinesia

Pifferi, Massimo; Bush, Andrew; Michelucci, Angela; Cicco, Maria Di; Piras, Martina; Caramella, Davide; Mazzei, Federica; Neri, M.; Pioggia, Giovanni; Tartarisco, Gennaro; Saggese, Giuseppe; Simi, Paolo; Boner, Attilio

doi:10.1002/ppul.23026

Cited by 17 publications

(19 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Beucher et al compared patients with abnormal and normal EM in a retrospective cohort of 89 children suspected of PCD, excluding 21 uncertain cases and found that only situs inversus differed significantly between the groups[14]. Pifferi et al compared clinical symptoms in 98 patients with primary PCD versus secondary ciliary dyskinesia; statistically significant differences were found for situs inversus and severity of bronchiectasis [15]. Mullowney et al , in the only publication that focused on neonates, compared neonatal symptoms between 46 PCD patients and 46 controls with a history of NRDS[16], and found that lobar collapse, situs inversus and prolonged oxygen need were more common in infants with PCD.…”

Section: Resultsmentioning

confidence: 99%

European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia

et al. 2016

Self Cite

View full text Add to dashboard Cite

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no ‘gold standard’ reference test. Hence, a task force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in the light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on: clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of PCD; also to provide advice when the diagnosis is not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for PCD.

show abstract

Section: Resultsmentioning

confidence: 99%

European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…A growing number of studies have investigated lung function in patients with PCD, and they fairly consistently show an inverse correlation between lung function and age, although there are clear differences within the PCD patient population. Interestingly, Davis et al demonstrated that lung disease is heterogeneous across all ultrastructural and genotype groups, but worse in those with absent IDA, CA defects, and MTD, most of whom had biallelic mutations in CCDC39 or CCDC40.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, MBL insufficiency is linked to irreversible lung damage after infection, such as postinfectious bronchiolitis, which could potentially lead to irreversible obstructive lung disease . A previous study found an association between bronchiectasis as documented by high‐resolution computed tomography (HRCT) and the MBL2 genotype in patients with PCD, but there was no association with cross‐sectional lung function values …”

Section: Introductionmentioning

confidence: 99%

The impact of mannose‐binding lectin polymorphisms on lung function in primary ciliary dyskinesia

Videbæk

Buchvald

Holgersen

et al. 2019

Pediatric Pulmonology

View full text Add to dashboard Cite

Objective Primary ciliary dyskinesia (PCD) is a congenital lung disease that leads to recurrent and chronic lung infection. The resulting inflammation causes lung damage and declines in lung function. Mannose‐binding lectin (MBL) is a first line host defense protein of importance for the innate immunity. Polymorphisms in the MBL gene named MBL2 result in unstable and low functional levels MBL proteins. MBL insufficiency is linked to an increased risk of lung infection and to declines in lung function in patients with cystic fibrosis. We investigated whether there is a similar link in patients with PCD. Methods This retrospective longitudinal study included 85 patients with PCD. Diagnostics and age at diagnosis were recorded, complete spirometry data starting at diagnosis, and Pseudomonas aeruginosa infection status over the last 2 years were collected, and the patients were grouped according to MBL2 genotype status (MBL2‐sufficient or MBL2‐deficient). Results MBL‐deficient patients were diagnosed almost 3 years earlier than MBL‐sufficient patients (median 6.1 vs 8.9 years, P < 0.05). There were no differences in the first measured spirometry values, but MBL‐deficient patients showed greater declines in forced expiratory volume in one sec (FEV1) than patients with MBL sufficiency (z‐score: −0.049 per year [95% CI, −0.075; −0.021] vs −0.009 per year [95% CI, −0.033; 0.015]; P = 0.023). No differences were found in forced vital capacity (FVC), FEV1/FVC, or infection status. Conclusion MBL‐deficiency, which is associated with MBL2 mutations, was associated with a lower age at diagnosis and with steeper declines in FEV1 in patients with PCD. This suggests that the MBL genotype might be a disease modifier in PCD.

show abstract

“…Since such responses are not necessarily unique to P. aeruginosa, this finding could have even broader implications, and requires further study. Additional defects in the complement system, particularly mannose-binding lectin deficiency have now been associated with more severe bronchiectasis in CF [30], common variable immunodeficiency [31], primary ciliary dyskinesia [32] and in a general population of patients with bronchiectasis [33].…”

Section: The Pathophysiology Of Bronchiectasis and The Goals Of Treatmentioning

confidence: 99%

Management of bronchiectasis in adults

2015

View full text Add to dashboard Cite

Formerly regarded as a rare disease, bronchiectasis is now increasingly recognised and a renewed interest in the condition is stimulating drug development and clinical research. Bronchiectasis represents the final common pathway of a number of infectious, genetic, autoimmune, developmental and allergic disorders and is highly heterogeneous in its aetiology, impact and prognosis.The goals of therapy should be: to improve airway mucus clearance through physiotherapy with or without adjunctive therapies; to suppress, eradicate and prevent airway bacterial colonisation; to reduce airway inflammation; and to improve physical functioning and quality of life.Fortunately, an increasing body of evidence supports interventions in bronchiectasis. The field has benefited greatly from the introduction of evidence-based guidelines in some European countries and randomised controlled trials have now demonstrated the benefit of long-term macrolide therapy, with accumulating evidence for inhaled therapies, physiotherapy and pulmonary rehabilitation.This review provides a critical update on the management of bronchiectasis focussing on emerging evidence and recent randomised controlled trials. @ERSpublications Bronchiectasis is a rapidly developing field: review of recent RCTs and progress towards developing new therapies

show abstract

Mannose-binding lectin 2 gene polymorphism and lung damage in primary ciliary dyskinesia

Abstract: MBL plays a relatively minor role as a disease modifier in PCD. A similar finding in SCD supports the likely significance of this result.

Cited by 17 publications

References 35 publications

European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia

European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia

The impact of mannose‐binding lectin polymorphisms on lung function in primary ciliary dyskinesia

Management of bronchiectasis in adults

Contact Info

Product

Resources

About