Lung disease in cystic fibrosis—an updated concept

Zach, M

doi:10.1002/ppul.1950080311

Cited by 98 publications

(46 citation statements)

References 105 publications

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“…Concerns that intensive and aggressive antibiotic treatment may eventually result in the occurrence of multiresistant P. aeruginosa strains [53,190], increased antibiotic toxicity or that such a treatment is very costintensive and may therefore only be applied to some CF patients [191], was not regarded as valid in this context by the members of the consensus meeting.…”

Section: Antibiotic Strategies Against Pseudomonas Aeruginosamentioning

confidence: 99%

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus

Döring¹,

Conway²,

Heijerman³

et al. 2000

Eur Respir J

559

478

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Cystic fibrosis (CF) is the most common lethal hereditary disorder with autosomal recessive heredity in caucasians. The majority of CF patients suffer from chronic respiratory infection with the opportunistic bacterial pathogen Pseudomonas aeruginosa. No consensus among clinicians has been reached so far concerning antibiotic treatment against P. aeruginosa in CF patients.Consensus answers to 24 important questions in this context, based on current evidence, are presented, given by a panel of 34 European experts. Questions addressed and answered are: The diagnosis of P. aeruginosa lung colonization in CF; The impact of P. aeruginosa on the clinical state of CF patients; The assessment of P. aeruginosa susceptibility against antibiotics and the importance of these results for the clinician; The use of monotherapy versus combination therapy; The development of microbial resistance; The achievement of optimal airway concentrations; The effects of subinhibitory concentrations of antibiotics on P. aeruginosa; Statements on the pharmacokinetics of antibiotics in CF patients; Recommendations for doses and dosing intervals and length of treatment regimens; and Toxic side effects due to repeated antibiotic therapy was addressed.The expert panel answered further questions on the use of fluoroquinolones in children with CF, on the administration of nebulized antibiotics and whether prevention of P. aeruginosa lung colonization is possible in CF using antibiotic therapy.Problems of antibiotic therapy at home and in the hospital were addressed, a consensus statement on regular maintenance treatment, or treatment on demand, was given and different routes of administration of antibiotics were recommended for different clinical situations.Finally, the factors which determine the choice of the antibiotic, the dosage, and the duration of the treatment in cystic fibrosis patients were addressed and the design of future antibiotic studies in the context of Pseudomonas aeruginosa lung infection in cystic fibrosis patients were recommended. Eur Respir J 2000; 16: 749±767.

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Section: Antibiotic Strategies Against Pseudomonas Aeruginosamentioning

confidence: 99%

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus

Döring¹,

Conway²,

Heijerman³

et al. 2000

Eur Respir J

559

478

View full text Add to dashboard Cite

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“…Clearance of the purulent pulmonary secretions in CF lung disease has long been enhanced through chest physiotherapy (350). Ironically, the universal acceptance of chest physiotherapy as a beneficial therapy in CF has led to a paucity of data supporting the tenet, probably due to the ethically tenuous nature of a long-term study comparing treatment with no treatment.…”

Section: Airway Clearancementioning

confidence: 99%

Lung Infections Associated with Cystic Fibrosis

2002

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While originally characterized as a collection of related syndromes, cystic fibrosis (CF) is now recognized as a single disease whose diverse symptoms stem from the wide tissue distribution of the gene product that is defective in CF, the ion channel and regulator, cystic fibrosis transmembrane conductance regulator (CFTR). Defective CFTR protein impacts the function of the pancreas and alters the consistency of mucosal secretions. The latter of these effects probably plays an important role in the defective resistance of CF patients to many pathogens. As the modalities of CF research have changed over the decades from empirical histological studies to include biophysical measurements of CFTR function, the clinical management of this disease has similarly evolved to effectively address the ever-changing spectrum of CF-related infectious diseases. These factors have led to the successful management of many CF-related infections with the notable exception of chronic lung infection with the gram-negative bacterium Pseudomonas aeruginosa. The virulence of P. aeruginosa stems from multiple bacterial attributes, including antibiotic resistance, the ability to utilize quorum-sensing signals to form biofilms, the destructive potential of a multitude of its microbial toxins, and the ability to acquire a mucoid phenotype, which renders this microbe resistant to both the innate and acquired immunologic defenses of the host

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“…IL-8 is the major chemokine associated with neutrophil migration across the airway epithelium (19), and it is found in increased amounts in the lungs of CF patients (9). Chronic influx of activated neutrophils into infected airways is responsible for damage to the airway and for progressive respiratory insufficiency in CF patients (47,53). As well as IL-8, other chemokines and cytokines were induced by 3-oxo-C 12 -HSL in other experimental systems (39).…”

mentioning

confidence: 99%

Differential Immune Modulatory Activity of Pseudomonas aeruginosa Quorum-Sensing Signal Molecules

Hooi¹,

Bycroft²,

Chhabra³

et al. 2004

Infect Immun

163

140

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Pseudomonas aeruginosa releases a spectrum of well-regulated virulence factors, controlled by intercellular communication (quorum sensing) and mediated through the production of small diffusible quorum-sensing signal molecules (QSSM). We hypothesize that QSSM may in fact serve a dual purpose, also allowing bacterial colonization via their intrinsic immune-modulatory capacity. One class of signal molecule, the N-acylhomoserine lactones, has pleiotropic effects on eukaryotic cells, particularly those involved in host immunity. In the present study, we have determined the comparative effects of two chemically distinct and endobronchially detectable QSSM, N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C 12 -HSL) and 2-heptyl-3-hydroxy-4 (1H)-quinolone or the Pseudomonas quinolone signal (PQS), on human leukocytes exposed to a series of stimuli designed to detect differential immunological activity in vitro. 3-Oxo-C 12 -HSL and PQS displayed differential effects on the release of interleukin-2 (IL-2) when human T cells were activated via the T-cell receptor and CD28 (a costimulatory molecule). 3-Oxo-C 12 -HSL inhibited cell proliferation and IL-2 release; PQS inhibited cell proliferation without affecting IL-2 release. Both molecules inhibited cell proliferation and the release of IL-2 following mitogen stimulation. Furthermore, in the presence of Escherichia coli lipopolysaccharide, 3-oxo-C 12 -HSL inhibited tumor necrosis factor alpha release from human monocytes, as reported previously (K. Tateda et al., Infect. Immun. 64:37-43, 1996), whereas PQS did not inhibit in this assay. These data highlight the presence of two differentially active immune modulatory QSSM from P. aeruginosa, which are detectable endobronchially and may be active at the host/pathogen interface during infection with P. aeruginosa, should the bronchial airway lymphoid tissues prove to be accessible to QSSM.

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Lung disease in cystic fibrosis—an updated concept

Cited by 98 publications

References 105 publications

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus

Lung Infections Associated with Cystic Fibrosis

Differential Immune Modulatory Activity of Pseudomonas aeruginosa Quorum-Sensing Signal Molecules

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