Update on cystic fibrosis epidemiology

Goss, Christopher H.; Rosenfeld, Margaret

doi:10.1097/01.mcp.0000138994.46519.72

Cited by 40 publications

(11 citation statements)

References 38 publications

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“…Clinical data for this cross-sectional study were obtained in 1995-1996, most of the siblings being born within or prior to the early 1980s. Thus, the patients enrolled for the study have survived a decade during which CF therapy was substantially improved and mortality among CF patients decreased considerably (Corey and Farewell 1996;Goss and Rosenfeld 2004;Liou et al 2001). It remains to be investigated in a CF population born later than our CF twins and sibs whether the improvement of the therapeutic regime could compensate for the inherent risk transmitted by 16p12 alleles mediated by SCNN1G and/or SCNN1B or by a common locus control element of these two ENaC subunits as proposed by Thomas et al (2002b).…”

Section: Modulation Of Cf Disease Severity At 16p12mentioning

confidence: 95%

“…Transmission disequilibrium of haplotype blocks was observed for the whole study population at both investigated loci implying that carriers of risk haplotypes were underrepresented when we recruited in 1995-1996 F508del-CFTR homozygous twins and siblings of at least 7 years of age. Median survival has increased from less than 10 years in the late 1970s to more than 30 years in the present patient population (Corey and Farewell 1996;Goss and Rosenfeld 2004) and correspondingly we can expect larger proportions of risk alleles in today's younger birth cohorts if patients from schoolchildren age to early adulthood are investigated. The depletion of risk alleles that was particularly prominent in the mildly affected subgroup of our study cohort is a strong argument that ENaC and TNFR1 are clinically highly relevant genetic modulators of CF disease.…”

Section: Implications For Pathophysiology and Clinic Of Cfmentioning

confidence: 96%

“…The multi-organ CF disease presents as a generalized exocrinopathy whereby the major affected organs are the gastrointestinal tract and the lung (Welsh et al 1995). Continuously improving treatment regimens have steadily increased the patients' survival and quality of life over the last decades (Littlewood 2000;Goss and Rosenfeld 2004).…”

Section: Introductionmentioning

confidence: 99%

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The TNFα receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium channel ENaC as modulators in cystic fibrosis

et al. 2006

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The CFTR mutations in cystic fibrosis (CF) lead to ion transport anomalities which predispose to chronic infection and inflammation of CF airways as the major determinants for morbidity and mortality in CF. Discordant clinical phenotypes of siblings with identical CFTR mutations and the large variability of clinical manifestations of patients who are homozygous for the most common mutation F508del suggest that both environment and genes other than CFTR contribute substantially to CF disease. The prime candidates for genetic modifiers in CF are elements of host defence such as the TNFalpha receptor and of ion transport such as the amiloride-sensitive epithelial sodium channel ENaC, both of which are encoded side by side on 12p13 (TNFRSF1A, SCNN1A) and 16p12 (SCNN1B, SCNN1G). Thirty-seven families with F508del-CFTR homozygous siblings exhibiting extreme clinical phenotypes that had been selected from the 467 pairs of the European CF Twin and Sibling Study were genotyped at 12p13 and 16p12 markers. The ENaC was identified as a modulator of CF by transmission disequilibrium at SCNN1G and association with CF phenotype intrapair discordance at SCNN1B. Family-based and case-control analyses and sequencing of SCNN1A and TNFRSF1A uncovered an association of the TNFRSF1A intron 1 haplotype with disease severity. Carriers of risk haplotypes were underrepresented suggesting a strong impact of both loci on survival. The finding that TNFRSF1A, SCNN1B and SCNN1G are clinically relevant modulators of CF disease supports current concepts that the depletion of airway surface liquid and inadequate host inflammatory responses trigger pulmonary disease in CF.

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Section: Modulation Of Cf Disease Severity At 16p12mentioning

confidence: 95%

Section: Implications For Pathophysiology and Clinic Of Cfmentioning

confidence: 96%

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The TNFα receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium channel ENaC as modulators in cystic fibrosis

et al. 2006

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“…Although median survival for the United Kingdom and the United States is similar, with approximately 35 years for both (2,9), patient and disease characteristics have been shown to vary, e.g., 40% of patients over 40 years in a United Kingdom CF center were pancreatic sufficient, compared to only 16% of patients in an equivalent U.S. center (17). There are many possible reasons why this may be the case, including socioeconomic factors, neonatal screening practices, and differences in treatment practices (14). Recommendations for the latter differ to some extent between the United Kingdom and United States (6,10,39).…”

mentioning

confidence: 95%

Analysis of the Bacterial Communities Present in Lungs of Patients with Cystic Fibrosis from American and British Centers

et al. 2011

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The aim of this study was to determine whether geographical differences impact the composition of bacterial communities present in the airways of cystic fibrosis (CF) patients attending CF centers in the United States or United Kingdom. Thirty-eight patients were matched on the basis of clinical parameters into 19 pairs comprised of one U.S. and one United Kingdom patient. Analysis was performed to determine what, if any, bacterial correlates could be identified. Two culture-independent strategies were used: terminal restriction fragment length polymorphism (T-RFLP) profiling and 16S rRNA clone sequencing. Overall, 73 different terminal restriction fragment lengths were detected, ranging from 2 to 10 for U.S. and 2 to 15 for United Kingdom patients. The statistical analysis of T-RFLP data indicated that patient pairing was successful and revealed substantial transatlantic similarities in the bacterial communities. A small number of bands was present in the vast majority of patients in both locations, indicating that these are species common to the CF lung. Clone sequence analysis also revealed that a number of species not traditionally associated with the CF lung were present in both sample groups. The species number per sample was similar, but differences in species presence were observed between sample groups. Cluster analysis revealed geographical differences in bacterial presence and relative species abundance. Overall, the U.S. samples showed tighter clustering with each other compared to that of United Kingdom samples, which may reflect the lower diversity detected in the U.S. sample group. The impact of cross-infection and biogeography is considered, and the implications for treating CF lung infections also are discussed.

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“…Among these are included several species of the genus Burkholderia whose incidence appears to be increasing; of the emerging pathogens, Bcc and B. gladioli, as also demonstrated in the present work, are prominent. 16 Between these microorganisms there is a high degree of phenotypic similarity and accurate identification is difficult. The use of a procedure based on a species-specific PCR for the identification …”

Section: Discussionmentioning

confidence: 99%

Burkholderia respiratory tract infections in Italian patients with cystic fibrosis: Molecular characterization

Allice

Scutera

Chirillo

et al. 2006

Journal of Infection

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Summary Objectives: To characterize by molecular techniques Burkholderia strains responsible for respiratory tract infections in cystic fibrosis (CF) patients (children and adults), to assign the Burkholderia cepacia complex (Bcc) isolates to a genomovar and to assess the presence of cblA and esmR genes in bacteria. Unique or sequential Burkholderia isolates (n ¼ 48) that had been collected from eight CF children and 17 adults over several (4e6) years were investigated; moreover 11 reference strains were analyzed. Methods: The microorganisms were identified by using biochemical methods, genotyped by pulse field gel electrophoresis (PFGE) and random-amplified polymorphic DNA fingerprintingePCR (RAPDePCR), and assessed by PCR assays for the genomovar and cblA and esmR genes of Bcc. Results: Among isolates 70.8% were identified as Bcc genomovar III-A; one child was infected by Burkholderia ambifaria and four adults were colonized with Burkholderia gladioli. The cblA gene was not detected in any of the isolates, while the esmR gene was detected in the 52.1% of the strains, all belonging to genomovar III-A. Conclusion: Molecular analysis of strains revealed in CF patients a colonization with a persistent Burkholderia flora with strains of one genotype. The prevalence of Bcc of genomovar III-A in the two categories of patients and of B. gladioli in four adults demonstrated that transmission may have occurred between subjects. Moreover the B. ambifaria infection demonstrated in a child may be environmentally derived.

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Update on cystic fibrosis epidemiology

Cited by 40 publications

References 38 publications

The TNFα receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium channel ENaC as modulators in cystic fibrosis

The TNFα receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium channel ENaC as modulators in cystic fibrosis

Analysis of the Bacterial Communities Present in Lungs of Patients with Cystic Fibrosis from American and British Centers

Burkholderia respiratory tract infections in Italian patients with cystic fibrosis: Molecular characterization

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