scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Update: cystic fibrosis.

01 Apr 1986-Pediatric Annals (SLACK Incorporated)-Vol. 15, Iss: 4, pp 296-304
About: This article is published in Pediatric Annals.The article was published on 1986-04-01. It has received 106 citations till now. The article focuses on the topics: Cystic fibrosis.
Citations
More filters
Book
01 Apr 2006
TL;DR: Advances in understanding and treatment of cystic fibrosis are summarized, focusing on pulmonary disease, which accounts for most morbidity and deaths.
Abstract: Cystic fibrosis is the most common autosomal recessive disorder in white people, with a frequency of about 1 in 2500 livebirths. Discovery of the mutated gene encoding a defective chloride channel in epithelial cells--named cystic fibrosis transmembrane conductance regulator (CFTR)--has improved our understanding of the disorder's pathophysiology and has aided diagnosis, but has shown the disease's complexity. Gene replacement therapy is still far from being used in patients with cystic fibrosis, mostly because of difficulties of targeting the appropriate cells. Life expectancy of patients with the disorder has been greatly increased over past decades because of better notions of symptomatic treatment strategies. Here, we summarise advances in understanding and treatment of cystic fibrosis, focusing on pulmonary disease, which accounts for most morbidity and deaths.

4,585 citations

Journal ArticleDOI
TL;DR: The global epidemiology of clonal P. aeruginosa strains in CF is described and the current literature regarding the underlying biology and clinical impact of globally important CF clones is summarized.
Abstract: Chronic lower airway infection with Pseudomonas aeruginosa is a major contributor to morbidity and mortality in individuals suffering from the genetic disease cystic fibrosis (CF). Whereas it was long presumed that each patient independently acquired unique strains of P. aeruginosa present in their living environment, multiple studies have since demonstrated that shared strains of P. aeruginosa exist among individuals with CF. Many of these shared strains, often referred to as clonal or epidemic strains, can be transmitted from one CF individual to another, potentially reaching epidemic status. Numerous epidemic P. aeruginosa strains have been described from different parts of the world and are often associated with an antibiotic-resistant phenotype. Importantly, infection with these strains often portends a worse prognosis than for infection with nonclonal strains, including an increased pulmonary exacerbation rate, exaggerated lung function decline, and progression to end-stage lung disease. This review describes the global epidemiology of clonal P. aeruginosa strains in CF and summarizes the current literature regarding the underlying biology and clinical impact of globally important CF clones. Mechanisms associated with patient-to-patient transmission are discussed, and best-evidence practices to prevent infections are highlighted. Preventing new infections with epidemic P. aeruginosa strains is of paramount importance in mitigating CF disease progression.

161 citations

Journal ArticleDOI
06 Mar 2014-PLOS ONE
TL;DR: This study investigated the reciprocal interaction of P. aeruginosa and S. aureus to gain important insight on the interplay occurring between the two main pathogens of CF airways, which is still largely unknown.
Abstract: Cystic fibrosis (CF) airways disease represents an example of polymicrobial infection whereby different bacterial species can interact and influence each other. In CF patients Staphylococcus aureus is often the initial pathogen colonizing the lungs during childhood, while Pseudomonas aeruginosa is the predominant pathogen isolated in adolescents and adults. During chronic infection, P. aeruginosa undergoes adaptation to cope with antimicrobial therapy, host response and co-infecting pathogens. However, S. aureus and P. aeruginosa often co-exist in the same niche influencing the CF pathogenesis. The goal of this study was to investigate the reciprocal interaction of P. aeruginosa and S. aureus and understand the influence of P. aeruginosa adaptation to the CF lung in order to gain important insight on the interplay occurring between the two main pathogens of CF airways, which is still largely unknown. P. aeruginosa reference strains and eight lineages of clinical strains, including early and late clonal isolates from different patients with CF, were tested for growth inhibition of S. aureus. Next, P. aeruginosa/S. aureus competition was investigated in planktonic co-culture, biofilm, and mouse pneumonia model. P. aeruginosa reference and early strains, isolated at the onset of chronic infection, outcompeted S. aureus in vitro and in vivo models of co-infection. On the contrary, our results indicated a reduced capacity to outcompete S. aureus of P. aeruginosa patho-adaptive strains, isolated after several years of chronic infection and carrying several phenotypic changes temporally associated with CF lung adaptation. Our findings provide relevant information with respect to interspecies interaction and disease progression in CF.

138 citations


Cites background from "Update: cystic fibrosis."

  • ...aeruginosa is considered to be the most significant as it has clearly been linked to worsening of the pulmonary status [21]....

    [...]

Journal ArticleDOI
TL;DR: Advances in techniques for analysis of mucociliary clearance have improved the understanding of the interaction between the respiratory epithelium and the airway surface liquid, resulting in the ability to study pathologic processes involving mucOCiliary clearance in great detail.
Abstract: Purpose of reviewMucociliary clearance is a critical host defense mechanism of the airways. Effective mucociliary clearance requires appropriate mucus production and coordinated ciliary activity. The important role of these two components is best demonstrated in disorders such as primary ciliary dys

131 citations

Journal ArticleDOI
TL;DR: The current state-of-the-art in vaccinology for Pseudomonas aeruginosa is described, including a discussion of those at risk for infection, the types of vaccines and the approaches for empirical and targeted antigen selection under development, as well as a perspective on where the field should go.
Abstract: Despite the recognition of Pseudomonas aeruginosa as an opportunistic pathogen, no vaccine against this bacteria has come to market. This review describes the current state-of-the-art in vaccinology for this bacterium. This includes a discussion of those at risk for infection, the types of vaccines and the approaches for empirical and targeted antigen selection under development, as well as a perspective on where the field should go. In addition, the challenges in developing a vaccine for those individuals at risk are discussed.

119 citations


Cites background from "Update: cystic fibrosis."

  • ...aeruginosa is multifactorial [39], including failure of clearance do to lack of CFTR-mediated bacterial internalization by epithelial cells [40], defective mucosal immunity [39], abnormally viscous secretions that impair mucociliary clearance [41] and, as demonstrated recently in the CF pig model, abnormal pH of the airway surface liquid [42]....

    [...]

References
More filters
Journal ArticleDOI
TL;DR: A method of performing the test for chloride or sodium in the sweat of patients with cystic fibrosis of the pancreas using pilocarpine by iontophoresis is presented and has the advantage of being both rapid and painless.
Abstract: A method of performing the test for chloride or sodium in the sweat of patients with cystic fibrosis of the pancreas is presented. It utilizes pilocarpine by iontophoresis and has the advantage of being both rapid and painless. Data are presented to show that the method is reliable.

1,258 citations

Journal ArticleDOI
TL;DR: The increased respiratory-epithelial potential differences appear to be a specific abnormality in homozygotes for cystic fibrosis, which suggests that absorption of excess salt and perhaps liquid from respiratory epithelial surfaces contributes to the pathogenesis of lung disease in cysts fibrosis.
Abstract: To investigate respiratory epithelial function in cystic fibrosis, we measured the transepithelial electrical potential difference across the upper and lower respiratory mucosa in patients with cystic fibrosis and control subjects. The nasal potential difference in the 24 patients with cystic fibrosis exceeded by more than 3 standard deviations the mean voltage in healthy controls, subjects with other diseases, and subjects heterozygous for cystic fibrosis. Potential differences in lower airways were measured in four patients and were significantly greater than in controls (P less than 0.05). Superfusion of the luminal surface with amiloride, an inhibitor of active sodium absorption, induced greater reductions in both nasal and airway potential difference in patients than in controls. We conclude that the increased respiratory-epithelial potential differences appear to be a specific abnormality in homozygotes for cystic fibrosis. The greater reduction in potential difference in response to amiloride suggests that absorption of excess salt and perhaps liquid from respiratory epithelial surfaces contributes to the pathogenesis of lung disease in cystic fibrosis.

583 citations

Journal ArticleDOI
TL;DR: Pulmonary function tests, including FEV1, FVC, FEF25%-75%, PaO2, and RV/TLC%, were significantly better in patients with normal fat absorption compared with both male and female patients who had steatorrhoea.

263 citations

Journal ArticleDOI
TL;DR: Neurological syndromes similar to those associated with abetalipoproteinaemia or Friedreich's ataxia developed in four patients with chronic steatorrhoea, two of whom had cystic fibrosis and two chronic cirrhosis of childhood, suggesting that spinocerebellar degeneration may be secondary to severe and prolonged vitamin E deficiency.

135 citations

Journal ArticleDOI
TL;DR: This study confirms that elevated IRT is characteristic of newborn babies with cystic fibrosis, and shows that this test is very specific and sensitive when used as a newborn screening test.

133 citations