Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype

Davis, Stephanie D.; Rosenfeld, Margaret; Lee, Hye-Seung; Ferkol, Thomas; Sagel, Scott D.; Dell, Sharon D.; Milla, Carlos; Pittman, Jessica E.; Shapiro, Adam J.; Sullivan, Kelli; Nykamp, Keith; Krischer, Jeffrey P.; Zariwala, Maimoona A.; Knowles, Michael R.; Leigh, Margaret W.

doi:10.1164/rccm.201803-0548oc

Cited by 144 publications

(137 citation statements)

References 37 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…In our study, PA colonized patients show worse chest CT score, as well as patients with number of exhacerbations > 2/year; FEV 1 did not differ between colonized and non-colonized patients, but this result may be attributed to the small number of patients with PA colonization in this study. However, although we have not carried out a longitudinal study, the rate of decline in FEV1 derived from age classes between the colonized and the noncolonized groups was similar to those reported previously by Cohen-Cymberknoh et al [18] and by Davis et al [42].…”

Section: Discussionsupporting

confidence: 87%

Exacerbations and Pseudomonas aeruginosa colonization are associated with altered lung structure and function in primary ciliary dyskinesia

et al. 2020

View full text Add to dashboard Cite

Background: Recurrent bacterial infections of the respiratory tract are one of the major clinical features of the primary ciliary dyskinesia (PCD), a rare genetic disease due to malfunctioning of motile cilia. Chronic infections and persistent inflammation of the respiratory system result in progressive lung disease. Aim of the study was to highlight the main factors associated with clinical, functional and anatomical deterioration in PCD patients. Methods: We retrospectively analyzed data from 58 patients with PCD, 37 adults and 21 children. The demographic and clinical data, forced expiratory volume at 1 s (FEV 1) and forced vital capacity (FVC), sputum microbiology and imaging results (chest CT scores-modified Bhalla) were recorded. Patients were stratified according to the number of exacerbations (< 2/year vs ≥ 2/year) and chronic Pseudomonas aeruginosa (PA) colonization. The possible correlations between lung function and chest CT scores were assessed; we also evaluated the correlation between these parameters and the severity scores for bronchiectasis (BSI, FACED and e-FACED). Results: Chest CT scores showed a significant correlation with FEV 1 (p = 0.0002), age (p < 0.0001), BMI (p = 0.0002) and number of lung lobes involved (p < 0.0001). PA colonization had an overall prevalence of 32.6%: no significant difference in FEV 1 between PA colonized and non-colonized patients was found (p = 0.70), while chest CT score was significantly worse in chronic PA colonized patients (p = 0.009). Patients with a high number of exacerbation (≥ 2/ year) were older (p = 0.01), had lower FEV 1 (p = 0.03), greater number of lobes involved (p < 0.001) and worse CT score than patients with low number of exacerbations (p = 0.001); they also had higher prevalence of PA chronic bronchial infection (33.3% versus 13.6%, p = 0.10). Multivariable linear regression analyses adjusted for gender, age and BMI showed positive associations between PA colonization and number of exacerbations with severity of disease (number of lobes involved, CT score, BSI, FACED, and e-FACED).

show abstract

Section: Discussionsupporting

confidence: 87%

Exacerbations and Pseudomonas aeruginosa colonization are associated with altered lung structure and function in primary ciliary dyskinesia

et al. 2020

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. This specific aspect was not the primary aim of our study but since ultrastructural defects seem to be important, we investigated whether any confounding by ultrastructural alterations, specifically IDA/CA/MTD, might explain our results although without finding any impact.…”

Section: Discussionmentioning

confidence: 99%

“…Unequal distribution of ciliary ultrastructural defects between the two groups was analyzed considering potential confounding influence, that is specifically it has been previously demonstrated that patients with absent inner dynein arm, central apparatus defects, and microtubular disorganization (IDA/CA/MTD) have worse outcomes in contrast to patients with other defects. 21 The lung function measurements originated from preplanned examinations and from measurements with possibly outcomedependent timing, for example during exacerbations and acute visits.…”

mentioning

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

“…Axonemal disorganization and inner dynein arm defects represent about 12% of all PCD cases, and mutations in CCDC39 and CCDC40 account for about 70% inner dynein arm defects with microtubular disorganization [2]. Interestingly, individuals with mutations in CCDC39 and CCDC40, and the axonemal disorganization and inner dynein arm defect group, have worse pulmonary function and more rapid decline compared to other PCD patients [34,35].…”

Section: Genes Encoding Nexin-dynein Regulatory Complex (N-drc) Compomentioning

confidence: 99%

Primary ciliary dyskinesia (PCD): A genetic disorder of motile cilia

Leigh

Horani

Kinghorn

et al. 2019

TRD

Self Cite

View full text Add to dashboard Cite

Primary ciliary dyskinesia (PCD) is a genetic disorder of motile cilia. Clinical features include chronic oto-sinopulmonary disease, laterality defects, and male fertility reflecting impaired function of respiratory cilia in the upper and lower respiratory tracts, nodal cilia in the embryonic node and sperm tails, respectively. Recent studies have identified over 40 PCD-associated genes that encode proteins involved in ciliary biogenesis, assembly, structure, or function. Mutations in these genes account for approximately 70% of PCD cases; therefore, further gene discovery is expected. The diagnosis of PCD is challenging because no single test has the required diagnostic accuracy. Recent efforts have focused on standardizing and validating a panel of tests (including assessment for key clinical features, nasal nitric oxide measurement, ciliary ultrastructure analysis, and PCD genetic testing) to be used at PCD Centers to accurately diagnose PCD. Multi-center research programs focused on PCD in North America and Europe have been crucial for PCD gene discovery, advancing our understanding of the natural history of PCD and launching multi-center clinical trials.

show abstract

Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype

Cited by 144 publications

References 37 publications

Exacerbations and Pseudomonas aeruginosa colonization are associated with altered lung structure and function in primary ciliary dyskinesia

Exacerbations and Pseudomonas aeruginosa colonization are associated with altered lung structure and function in primary ciliary dyskinesia

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

Primary ciliary dyskinesia (PCD): A genetic disorder of motile cilia

Contact Info

Product

Resources

About