Analysis of CFTR Gene Variants in Idiopathic Bronchiectasis in Serbian Children

Milošević, Katarina; Nikolić, Aleksandra; Rankov, Aleksandra Divac; Ljujić, Mila; Nestorovic, Branimir; Radojković, Dragica

doi:10.1089/ped.2013.0238

Cited by 10 publications

(7 citation statements)

References 36 publications

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“…Based on the proposed new classification of variants identified in this work (Table 1), 16 patients with DB and 14 controls (ns; p = 0.82) have at least one variant with no neutral in vitro effect. Concerning the DB population, this is not different from other studies except when they did not sequence all CFTR exonic regions [23] (p = 0.0257; Supplementary table 5). For the control group, this number seems to be higher than in the two other studies, but the difference is not significant ([5] p = 0.21; [7] p = 0.14).…”

Section: Discussioncontrasting

confidence: 68%

Should diffuse bronchiectasis still be considered a CFTR-related disorder?

Bergougnoux

Viart

Miro

et al. 2015

Journal of Cystic Fibrosis

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Section: Discussioncontrasting

confidence: 68%

Should diffuse bronchiectasis still be considered a CFTR-related disorder?

Bergougnoux

Viart

Miro

et al. 2015

Journal of Cystic Fibrosis

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“…The observation that people heterozygous for a CF-causing CFTR mutation had normal rates of airway epithelial Cl − secretion made it difficult to understand why such individuals have an increased risk of airway disease (19)(20)(21)(22)(23)(24)(25)(26)(27). Our data provide a potential explanation.…”

Section: As Hcomentioning

confidence: 85%

“…However, conclusions from those studies are limited because Vt does not provide a quantitative measure of ion transport, mice do not develop CF airway disease, and infection and inflammation may produce secondary alterations in transepithelial electrolyte transport. Despite evidence of similar Cl − transport, CF carriers are predisposed to airway sinus disease (19)(20)(21), bronchiectasis (22,23), and asthma (24)(25)(26)(27). Those findings suggest that airway host defense might be impaired in CF carriers and that measures of transepithelial Cl − secretion may not be sufficiently sensitive to detect a mild abnormality.…”

mentioning

confidence: 99%

Relationships among CFTR expression, HCO ₃ ⁻ secretion, and host defense may inform gene- and cell-based cystic fibrosis therapies

Shah

Ernst

Tang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. Airway disease is the major source of morbidity and mortality. Successful implementation of gene- and cell-based therapies for CF airway disease requires knowledge of relationships among percentages of targeted cells, levels of CFTR expression, correction of electrolyte transport, and rescue of host defense defects. Previous studies suggested that, when ∼10–50% of airway epithelial cells expressed CFTR, they generated nearly wild-type levels of Cl− secretion; overexpressing CFTR offered no advantage compared with endogenous expression levels. However, recent discoveries focused attention on CFTR-mediated HCO3− secretion and airway surface liquid (ASL) pH as critical for host defense and CF pathogenesis. Therefore, we generated porcine airway epithelia with varying ratios of CF and wild-type cells. Epithelia with a 50:50 mix secreted HCO3− at half the rate of wild-type epithelia. Likewise, heterozygous epithelia (CFTR+/− or CFTR+/∆F508) expressed CFTR and secreted HCO3− at ∼50% of wild-type values. ASL pH, antimicrobial activity, and viscosity showed similar relationships to the amount of CFTR. Overexpressing CFTR increased HCO3− secretion to rates greater than wild type, but ASL pH did not exceed wild-type values. Thus, in contrast to Cl− secretion, the amount of CFTR is rate-limiting for HCO3− secretion and for correcting host defense abnormalities. In addition, overexpressing CFTR might produce a greater benefit than expressing CFTR at wild-type levels when targeting small fractions of cells. These findings may also explain the risk of airway disease in CF carriers.

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“…CFTR abnormalities [192][193][194] Two genes or homozygous state produces CF genotype. Almost 2,000 mutations in the CFTR gene have been identified in people with CF.…”

Section: Recurrent Sinopulmonary Infections In Cvidmentioning

confidence: 99%

Pediatric bronchiectasis: No longer an orphan disease

Goyal

Grimwood

Marchant

et al. 2016

Pediatric Pulmonology

131

140

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Bronchiectasis is described classically as a chronic pulmonary disorder characterized by a persistent productive cough and irreversible dilatation of one or more bronchi. However, in children unable to expectorate, cough may instead be wet and intermittent and bronchial dilatation reversible in the early stages. Although still considered an orphan disease, it is being recognized increasingly as causing significant morbidity and mortality in children and adults in both affluent and developing countries. While bronchiectasis has multiple etiologies, the final common pathway involves a complex interplay between the host, respiratory pathogens and environmental factors. These interactions lead to a vicious cycle of repeated infections, airway inflammation and tissue remodelling resulting in impaired airway clearance, destruction of structural elements within the bronchial wall causing them to become dilated and small airway obstruction. In this review, the current knowledge of the epidemiology, pathobiology, clinical features, and management of bronchiectasis in children are summarized. Recent evidence has emerged to improve our understanding of this heterogeneous disease including the role of viruses, and how antibiotics, novel drugs, antiviral agents, and vaccines might be used. Importantly, the management is no longer dependent upon extrapolating from the cystic fibrosis experience. Nevertheless, substantial information gaps remain in determining the underlying disease mechanisms that initiate and sustain the pathophysiological pathways leading to bronchiectasis. National and international collaborations, standardizing definitions of clinical and research end points, and exploring novel primary prevention strategies are needed if further progress is to be made in understanding, treating and even preventing this often life-limiting disease.

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Analysis of CFTR Gene Variants in Idiopathic Bronchiectasis in Serbian Children

Cited by 10 publications

References 36 publications

Should diffuse bronchiectasis still be considered a CFTR-related disorder?

Should diffuse bronchiectasis still be considered a CFTR-related disorder?

Relationships among CFTR expression, HCO ₃ ⁻ secretion, and host defense may inform gene- and cell-based cystic fibrosis therapies

Pediatric bronchiectasis: No longer an orphan disease

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Analysis of CFTR Gene Variants in Idiopathic Bronchiectasis in Serbian Children

Cited by 10 publications

References 36 publications

Should diffuse bronchiectasis still be considered a CFTR-related disorder?

Should diffuse bronchiectasis still be considered a CFTR-related disorder?

Relationships among CFTR expression, HCO 3 − secretion, and host defense may inform gene- and cell-based cystic fibrosis therapies

Pediatric bronchiectasis: No longer an orphan disease

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Product

Resources

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Relationships among CFTR expression, HCO ₃ ⁻ secretion, and host defense may inform gene- and cell-based cystic fibrosis therapies