Clinical Manifestations of Cystic Fibrosis Among Patients With Diagnosis in Adulthood

Gilljam, M.; Ellis, Lynda; Corey, Mary; Zielenski, Julian; Durie, Peter R.; Tullis, D. Elizabeth

doi:10.1378/chest.126.4.1215

Cited by 115 publications

(86 citation statements)

References 48 publications

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“…CFTR-mediated chloride diffusion potential was determined by first perfusing with amiloride and a chloride-free solution (⌬Cl Ϫ -free) followed by isoproterenol (⌬Cl Ϫ -free ϩ Iso). Because the diagnostic reference limits for nasal PD have not been established, we used ⌬Cl Ϫ -free ϩ Iso values below the lower 99% confidence limits for controls (Ϫ7.65 mV) as a conservative indicator of CF disease (27). Sweat chloride tests were performed by the Gibson and Cooke method (28) on the same day as the PD measurements.…”

Section: Nasal Potential Difference and Sweat Chloridementioning

confidence: 99%

Mutations in the Cystic Fibrosis Transmembrane Regulator Gene andIn VivoTransepithelial Potentials

Wilschanski

Dupuis²,

Ellis³

et al. 2006

Am J Respir Crit Care Med

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161

108

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Aim: To examine the relationship between cystic fibrosis transmembrane regulator gene mutations (CFTR) and in vivo transepithelial potentials. Methods: We prospectively evaluated 162 men including 31 healthy subjects, 21 obligate heterozygotes, 60 with congenital bilateral absence of the vas deferens (CBAVD) and 50 with CF by extensive CFTR genotyping, sweat chloride and nasal potential difference testing. Results: Six (10%) men with CBAVD carried no CFTR mutations, 18 (30%) carried one mutation, including the 5T variant, and 36 (60%) carried mutations on both alleles, for a significantly higher rate carrying one or more mutations than healthy controls (90% versus 19%, p Ͻ 0.001). There was an overlapping spectrum of ion channel measurements among the men with CBAVD, ranging from values in the control and obligate heterozygote range at one extreme, to values in the CF range at the other. All pancreatic-sufficient patients with CF and 34 of 36 patients with CBAVD with mutations on both alleles carried at least one mild mutation. However, the distribution of mild mutations in the two groups differed greatly. Genotyping, sweat chloride and nasal potential difference (alone or in combination) excluded CF in all CBAVD men with no mutations. CF was confirmed in 56% and 67% of CBAVD men carrying 1 and 2 CFTR mutations, respectively. Conclusion: Abnormalities of CFTR transepithelial function correlate with the number and severity of CFTR gene mutations.Keywords: CFTR mutations; congenital bilateral absence of the vas deferens; cystic fibrosis; nasal potential difference; sweat chlorideThe heterogeneity of cystic fibrosis (CF) disease is partially explained by more than 1,300 different mutations in the CFTR gene (1). Most classically diagnosed patients with CF carry severe loss-of-function mutations on both alleles and have evidence of pancreatic insufficiency (PI) (2). Those with nonclassic CF carry a mild CFTR gene mutation on at least one allele, and usually retain sufficient residual pancreatic function to confer pancreatic sufficiency (PS) (3-6). Patients with PS are usually diagnosed in adolescence or adulthood with less severe symptoms and variable but generally milder pulmonary disease. Most men with CF are infertile due to obstructive azoospermia, which in its severest form presents as congenital bilateral absence of the vas deferens (CBAVD) (7-10). CBAVD also occurs in 1 to 2% of infertile males who are otherwise healthy, the majority of whom carry CFTR gene mutations on one or both alleles (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Typically, the CFTR genotype in men with CBAVD includes at least one "mild" missense or splice variant. Similar combinations of CFTR gene mutations have been observed in patients with other CFTRassociated phenotypes, including idiopathic chronic pancreatitis (21-23) and chronic sinusitis (24), but the frequency of gene mutations in these patients is lower than in men with CBAVD.The relation between the number and severity of CFTR gene mutations and the degree of CFTR-mediated dysfunc...

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Section: Nasal Potential Difference and Sweat Chloridementioning

confidence: 99%

Mutations in the Cystic Fibrosis Transmembrane Regulator Gene andIn VivoTransepithelial Potentials

Wilschanski

Dupuis²,

Ellis³

et al. 2006

Am J Respir Crit Care Med

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161

108

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“…Various studies in the literature have shown that CF patients diagnosed in adulthood present worse systemic and pulmonary evolution. (18,19) The worse pulmonary function observed in the patients of the present study suggests the possibility of late diagnosis in individuals who presented symptoms since childhood and who, for lack of specialized medical assistance, did not receive specific treatment in a timely manner.…”

mentioning

confidence: 68%

Deve-se extrapolar o tratamento de bronquiectasias em pacientes com fibrose cística para aqueles com bronquiectasias de outras etiologias?

et al. 2010

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OBJETIVO: Conhecer o perfil de pacientes adultos com bronquiectasias, comparando portadores de fibrose cística (FC) com aqueles com bronquiectasias de outra etiologia, a fim de determinar se é racional extrapolar terapêuticas instituídas em fibrocísticos para aqueles com bronquiectasias de outras etiologias. MÉTODOS: Análise retrospectiva dos prontuários de 87 pacientes adultos com diagnóstico de bronquiectasia em acompanhamento em nosso serviço. Pacientes com doença secundária a infecção por tuberculose corrente ou no passado foram excluídos. Foram avaliados dados clínicos, funcionais e terapêuticos dos pacientes. RESULTADOS: Dos 87 pacientes com bronquiectasias, 38 (43,7%) tinham diagnóstico confirmado de FC através de dosagem de sódio e cloro no suor ou análise genética, enquanto 49 (56,3%) apresentavam a doença por outra etiologia, 34 (39,0%) desses com bronquiectasia idiopática. Os pacientes com FC apresentavam média de idade ao diagnóstico mais baixa (14,2 vs. 24,2 anos; p < 0,05). A prevalência de sintomas (tosse, expectoração, hemoptise e sibilância) foi semelhante entre os grupos. A colonização por Pseudomonas aeruginosa e a por Staphylococcus aureus foram mais comuns nos pacientes com FC (82,4 vs. 29,7% e 64,7 vs. 5,4%, respectivamente). CONCLUSÕES: As causas e as manifestações clínicas das bronquiectasias são heterogêneas, sendo importante a identificação dessas diferenças na abordagem do paciente. Reconhecer estas diferenças é crucial para o desenvolvimento de novas estratégias para o manejo de pacientes com bronquiectasias.

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“…Another factor that contributes to the diagnostic difficulty is that a considerable number of these patients present normal or borderline sweat test results. (15)(16)(17) One group of authors described 28 cases of patients living in Salvador, Brazil and diagnosed with CF in adult life. (18) The mean age was 31.1 years, 53.7% were black or mulatto, and 43% presented P. aeruginosa in the sputum culture.…”

Section: Antibiotic Therapymentioning

confidence: 99%

“…Although determining the NPD might be useful, the difficulty in standardizing the test is a limiting factor in clinical practice. (15) In the absence of gastrointestinal symptoms, the differential diagnosis should include ciliary dyskinesia, deficiency of immunoglobulin G, and Young's syndrome. (5) treatment to eradicate the pathogen and prevent chronic infection has been recommended.…”

Section: Antibiotic Therapymentioning

confidence: 99%

Fibrose cística no adulto: aspectos diagnósticos e terapêuticos

Dalcin¹,

Silva²

2008

J. bras. pneumol.

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Once considered a childhood disease, cystic fibrosis is now also a disease of adults. Increased longevity has resulted in the aging of the cystic fibrosis population. The consequent age-related medical problems among adults with cystic fibrosis have increased medical care needs. These needs are being met by a growing number of nonpediatric pulmonologists and other nonpediatric specialists. The objective of this review was to summarize the current knowledge about diagnosis and treatment in adult cystic fibrosis. In most cases, the diagnosis is suggested by manifestations of chronic sinopulmonary disease and exocrine pancreatic insufficiency. The diagnosis is confirmed by a positive sweat test result. Adult patients may, however, present pancreatic sufficiency and atypical clinical features, sometimes in combination with normal or borderline sweat test results. In such cases, identifying cystic fibrosis mutations and measuring nasal potential difference can have diagnostic utility. The standard therapeutic approach to pulmonary disease includes the use of antibiotics, airway clearance, exercise, mucolytics, bronchodilators, oxygen therapy, anti-inflammatory agents and nutritional support. Appropriate application of these therapies results in most cystic fibrosis patients surviving into adulthood with an acceptable quality of life.

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Clinical Manifestations of Cystic Fibrosis Among Patients With Diagnosis in Adulthood

Cited by 115 publications

References 48 publications

Mutations in the Cystic Fibrosis Transmembrane Regulator Gene andIn VivoTransepithelial Potentials

Mutations in the Cystic Fibrosis Transmembrane Regulator Gene andIn VivoTransepithelial Potentials

Deve-se extrapolar o tratamento de bronquiectasias em pacientes com fibrose cística para aqueles com bronquiectasias de outras etiologias?

Fibrose cística no adulto: aspectos diagnósticos e terapêuticos

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