Mucoid Pseudomonas aeruginosa in cystic fibrosis

Henry, Richard L.; Dorman, David C.; Brown, John J.; Mellis, Craig

doi:10.1111/j.1440-1754.1982.tb01979.x

Cited by 151 publications

(181 citation statements)

References 6 publications

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“…It is the emergence of the mucoid phenotype that is clearly associated with a significantly increased rate in the decline in CF lung function [3,24]. Emergence of the mucoid phenotype is associated with genetic mutations in the algU-mucABCD gene cluster [48][49][50].…”

Section: Establishment Of Chronic Infectionmentioning

confidence: 99%

“…Another strategy to consider is the use of immunotherapy against P. aeruginosa, focused on either preventing the initial colonization with non-mucoid strains or limiting the infection to these less-pathogenic types [24] while preventing conversion and emergence of the more virulent mucoid phenotype [69]. Although the innate immune response in CF patients is ineffective in clearing P. aeruginosa from the lungs early in the course of infection, it might be possible to use the acquired immune system to provide protective immunity.…”

Section: Preventing or Limiting The Development Of Infectionmentioning

confidence: 99%

“…An interesting observation made in Danish CF patients suggests that two highly transmissible clones can be isolated from many different patients within their Copenhagen center, suggesting an ability of evolutionarily successful P. aeruginosa variants to supplant environmentally acquired strains and be a significant cause of lung function decline and disease progression [22]. However, current findings still indicate that the most profound increases in the rate of lung function decline occur when P. aeruginosa undergoes genotypic changes, leading to a mucoid phenotype characterized by over-production of a surface polysaccharide known as alginate and the loss of the ability to produce lipopolysaccharide (LPS) O side chains [3,24]. Numerous other genetic changes have been identified in mucoid isolates from CF patients [25], indicating that multiple genetic adaptations confer increased resistance to the innate and acquired host immune defenses and to antibiotic therapy [1,16,17].…”

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confidence: 99%

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Airway epithelial control of Pseudomonas aeruginosa infection in cystic fibrosis

Campodónico

Gadjeva

Paradis-Bleau

et al. 2008

Trends in Molecular Medicine

100

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Defective expression or function of the cystic fibrosis transmembrane conductance regulator (CFTR) underlies the hypersusceptibility of cystic fibrosis (CF) patients to chronic airway infections, particularly with Pseudomonas aeruginosa. CFTR is involved in the specific recognition of P. aeruginosa, thereby contributing to effective innate immunity and proper hydration of the airway surface layer (ASL). In CF, the airway epithelium fails to initiate an appropriate innate immune response, allowing the microbe to bind to mucus plugs that are then not properly cleared because of the dehydrated ASL. Recent studies have identified numerous CFTR-dependent factors that are recruited to the epithelial plasma membrane in response to infection and that are needed for bacterial clearance, a process that is defective in CF patients hypersusceptible to infection with this organism. Pseudomonas aeruginosa in cystic fibrosisCystic fibrosis (CF) is unique among human genetic disorders in that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a protein whose primary function described to date has been to regulate conductance of ions in and out of cells and intracellular vacuoles, lead to hypersusceptibility to chronic lung infection. Human diseases wherein individuals homozygous for mutant genes are predisposed to infections serve as a firm foundation for understanding the molecular, cellular, physiologic and immunologic aspects of normal and compromised resistance to infection. CF is not just a prime example of how we can learn about normal and pathologic states; it could, in fact, be the only known human genetically determined disease wherein infection with a single pathogen -Pseudomonas aeruginosa -drives the vast majority of morbidity, clinical deterioration and ultimately life-shortening mortality encountered in this disease. In humans with significant compromises to their immune system, such as advanced AIDS, we would normally expect to see a plethora of pathogens take advantage of this debilitated state, but this is not the case in CF.CF is characterized by the emergence and persistence of (and, ultimately, the inability to clear) chronic infection with a variant of P. aeruginosa (mucoid P. aeruginosa) that overproduces a surface polysaccharide known as alginate. The organism undergoes other significant genetic adaptations and selections within the CF lung, and it is the emergence of mucoid P. aeruginosa that is the primary determinant of the clinical course of this disease [1,2]. In those individuals with either an uncommon but fortuitous protective immune response to specific P. aeruginosa antigens [3,4] Histopathologic basis for defining relevant interactions between P.aeruginosa and the CF airway epitheliumAlthough CF is a multisystem disease characterized by GI and nutritional abnormalities, salt loss syndromes and male urogenital abnormalities, the major clinical problem for CF patients is chronic sinopulmonary disease. Therefore, relying on observations made fr...

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Section: Establishment Of Chronic Infectionmentioning

confidence: 99%

Section: Preventing or Limiting The Development Of Infectionmentioning

confidence: 99%

mentioning

confidence: 99%

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Airway epithelial control of Pseudomonas aeruginosa infection in cystic fibrosis

Campodónico

Gadjeva

Paradis-Bleau

et al. 2008

Trends in Molecular Medicine

100

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“…1 P. aeruginosa infection is associated with accelerated decline in lung function and is a significant predictor of mortality in CF. 2 Therefore, effective treatment of P. aeruginosa infection is central to the management of CF lung disease.…”

Section: Introductionmentioning

confidence: 99%

A phase 2 study of aztreonam lysine for inhalation to treat patients with cystic fibrosis and Pseudomonas aeruginosa infection

Retsch‐Bogart¹,

Burns

Otto³

et al. 2007

Pediatric Pulmonology

100

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Summary. Background: Aztreonam lysine for inhalation (AZLI) is being developed for treatment of CF patients with Pseudomonas aeruginosa airway infection. Methods: This double-blind, randomized, placebo-controlled Phase 2 study evaluated the safety, tolerability and efficacy of 75 and 225 mg AZLI administered BID for 14 days using the eFlow 1 Electronic Nebulizer (Pari Innovative Manufacturers, Inc., Midlothian, VA). Patients were 13 years and older with FEV 1 ! 40% predicted, chronic P. aeruginosa infection, and had used no anti-pseudomonal antibiotics for 56 days. Results: Of 131 patients screened, 105 received AZLI or placebo. Mean age was 26 years and mean FEV 1 percent predicted was 77% at baseline. There was a statistically significant reduction, compared to placebo, in P. aeruginosa CFU density in each AZLI group at Days 7 and 14 (P < 0.001). The planned primary analysis, percent change in FEV 1 at Day 14, demonstrated no statistically significant difference. Post hoc analysis demonstrated significant increase in FEV 1 at Day 7 for the subset of patients with baseline FEV 1 < 75% predicted in the 225 mg AZLI group. Bronchodilator use was associated with greater improvement in FEV 1 , as well as greater reduction in P. aeruginosa bacterial density and higher plasma aztreonam concentrations in the 225 mg AZLI group. Adverse events were similar between placebo and AZLI although there was a trend toward

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“…Sarajevo 15 21 29 38 36 17 28 9 22 56 38 42 Tested in others cantons 31 27 26 28 30 31 43 12 11 9 13 11 Tested in all cantons 46 48 55 66 66 48 71 21 33 65 51 treatment of CF. In this sense, nowadays there are many therapeutic strategies that must be counted and the possibility of active immunization against bacterial and viral infections (19). By 18 years of age, 80% of patients with classic CF harbor P. aeruginosa, and 3.5% harbor B. cepacia (20).…”

Section: Discussionmentioning

confidence: 99%

The Analysis of Cystic Fibrosis in the Federation of Bosnia and Herzegovina

Selimović¹,

Mujičić²,

Milisic³

et al. 2016

RAD Conference Proceedings

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Aim:The aim of this study is to present the first total number of tested children in the Federation of Bosnia and Herzegovina and the number of children with positive sweat test. During the study we determined the number of ill children, the median age of children with cystic fibrosis, date of initial diagnosis, an average amount of chloride in the sweat. Material and methods: The study was a retrospective, conducted at the Department of Pulmonology Pediatric Clinic of University Clinical Center of Sarajevo. Results: In the period from March 2003 to December 2014, we have tested 625 children. 351 child were from Sarajevo Canton and 272 children from other cantons. Female children were more affected then male children, in the ratio of 1: 1,105. An average age of female children was 4.19±4.26 years, and the male 2.15±3.11 years. The median concentration of chloride in the sweat measured by sweat test was for male children 103.05±21.29 mmol/L, and for the female children 96.05±28.85 mmol/L. Conclusion: Most of children in Federation of Bosnia and Herzegovina have ∆F508 gene mutation. In the post-war period we started to use a sweat test. Male children tend to live longer than female children with CF.

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Mucoid Pseudomonas aeruginosa in cystic fibrosis

Cited by 151 publications

References 6 publications

Airway epithelial control of Pseudomonas aeruginosa infection in cystic fibrosis

Airway epithelial control of Pseudomonas aeruginosa infection in cystic fibrosis

A phase 2 study of aztreonam lysine for inhalation to treat patients with cystic fibrosis and Pseudomonas aeruginosa infection

The Analysis of Cystic Fibrosis in the Federation of Bosnia and Herzegovina

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