Lung Infections Associated with Cystic Fibrosis

Lyczak, Jeffrey B.; Cannon, Carolyn L.; Pier, Gerald B.

doi:10.1128/cmr.15.2.194-222.2002

Cited by 1,425 publications

(1,417 citation statements)

References 353 publications

Supporting

Mentioning

1,335

Contrasting

Unclassified

Order By: Relevance

“…It has been proposed that they might damage the epithelial surfaces, leading to increased attachment of P. aeruginosa [16]. However, their role in the pathogenesis of lung disease continues to be a topic of discussion, as well as whether treating these infections has clinical benefit.…”

Section: Early Pathogens: Staphylococcus Aureus and Haemophilus Influmentioning

confidence: 99%

“…aeruginosa strains that initiate infections in CF can produce a huge arsenal of metabolic and virulence factors [16], can use the nutrients in the lung to promote growth [52] and can synthesize many toxic factors, such as pyocyanin, a type III secretion system, a variety of proteases, lipases and phospholipases, rhamnolipids and other potentially toxic factors [16,21,53]. Another key change in the organism associated with virulence in the CF lung is the loss of synthesis of the LPSO side chain [54] combined with the synthesis of the lipid A component as an isoform more likely to promote inflammation [55].…”

Section: Establishment Of Chronic Infectionmentioning

confidence: 99%

“…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]. This makes eradication of mucoid P. aeruginosa from the CF lung practically impossible.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Airway epithelial control of Pseudomonas aeruginosa infection in cystic fibrosis

Campodónico

Gadjeva

Paradis-Bleau

et al. 2008

Trends in Molecular Medicine

Self Cite

100

View full text Add to dashboard Cite

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...

show abstract

Section: Early Pathogens: Staphylococcus Aureus and Haemophilus Influmentioning

confidence: 99%

Section: Establishment Of Chronic Infectionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Airway epithelial control of Pseudomonas aeruginosa infection in cystic fibrosis

Campodónico

Gadjeva

Paradis-Bleau

et al. 2008

Trends in Molecular Medicine

Self Cite

100

View full text Add to dashboard Cite

show abstract

“…To deal with these problems, recent work has focused on "large porous" particles exhibiting geometric diameters larger than 10 μm but with aerodynamic diameters of ∼1-3 μm [14][15][16][17]. Large porous particles exhibit the aerodynamics of smaller particles while maintaining a size large enough to resist uptake by alveolar macrophages [18]; however, a narrow aerodynamic diameter is still desired. The aerodynamic diameter of a porous particle is given by eqn.…”

Section: Introductionmentioning

confidence: 99%

NanoCipro encapsulation in monodisperse large porous PLGA microparticles

Arnold

Gorman

Schieber

et al. 2007

Journal of Controlled Release

117

View full text Add to dashboard Cite

Pulmonary drug delivery of controlled release formulations may provide an effective adjunct approach to orally delivered antibiotics for clearing persistent lung infections. Dry powder formulations for this indication should possess characteristics including; effective deposition to infected lung compartments, persistence at the infection site, and steady release of antibiotic. Large porous particles (∼10-15 μm) have demonstrated effective lung deposition and enhanced lung residence as a result of their large diameter and reduced clearance by macrophages in comparison to small microparticles (∼1-5 μm). In this report, Precision Particle Fabrication technology was used to create monodisperse large porous particles of poly(D,L-lactic-co-glycolic acid) (PLGA) utilizing oils as extractable porogens. After extraction, the resulting large porous PLGA particles exhibited a low density and a web-like or hollow interior depending on porogen concentration and type, respectively. Ciprofloxacin nanoparticles (nanoCipro) created by homogenization in dichloromethane, possessed a polymorph with a decreased melting temperature. Encapsulating nanoCipro in large porous PLGA particles resulted in a steady release of ciprofloxacin that was extended for larger particle diameters and for the solid particle morphology in comparison to large porous particles. The encapsulation efficiency of nanoCipro was quite low and factors impacting the entrapment of nanoparticles during particle formation were elucidated. A dry powder formulation with the potential to control particle deposition and sustain release to the lung was developed and insight to improve nanoparticle encapsulation is discussed.

show abstract

“…It is also the most dominant bacterial pathogen that can be recovered from the chronically infected lung of cystic fibrosis (CF) patients [1][2][3][4]. Antimicrobial therapy has made an important contribution to increase the life expectancy of CF patients and is one of the cornerstones of the treatment of the disease [5,6].…”

Section: Introductionmentioning

confidence: 99%