Advances in cystic fibrosis therapies
Current Opinion in PediatricsPublished 10 November 2006
Steven M. Rowe, John P. Clancy
Citations54
SJR quartileQ1
SJR score0.83
SNIP0.90
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
This review describes recent developments in cystic fibrosis pulmonary therapies intended to treat various facets of the disease, including several treatments currently in development.
Abstract
Recent advances in therapies for cystic fibrosis offer the promise of improved outcomes and longer lives for patients with cystic fibrosis.
Keywords
Medicine
ScienceIdentification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNA
7,425 Citations1989John R. Riordan, Johanna M. Rommens +12 more
A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients.
ScienceIdentification of the Cystic Fibrosis Gene: Genetic Analysis
4,129 Citations1989Bat-Sheva Kerem, Johanna M. Rommens +6 more
Extended haplotype data based on DNA markers closely linked to the putative disease gene locus suggest that the remainder of the cystic fibrosis mutant gene pool consists of multiple, different mutations.
ScienceIdentification of the Cystic Fibrosis Gene: Chromosome Walking and Jumping
3,241 Citations1989Johanna M. Rommens, Michael C. Iannuzzi +13 more
Several transcribed sequences and conserved segments were identified in this cloned region and one corresponds to the cystic fibrosis gene and spans approximately 250,000 base pairs of genomic DNA.
New England Journal of MedicineRole of Transforming Growth Factor β in Human Disease
2,406 Citations2000Gerard C. Blobe, William P. Schiemann +1 more
In human tissues, normal homeostasis requires intricately balanced interactions between cells and the network of secreted proteins known as the extracellular matrix, which is clearly evident in the interactions mediated by the cytokine transforming growth factor β (TGF-β).
American Journal of Respiratory and Critical Care MedicinePathophysiology and Management of Pulmonary Infections in Cystic Fibrosis
1,630 Citations2003Ronald L. Gibson, Jane L. Burns +1 more
This comprehensive State of the Art review summarizes the current published knowledge base regarding the pathophysiology and microbiology of pulmonary disease in cystic fibrosis and potential future therapies.
Annual Review of BiochemistryMammalian ABC Transporters in Health and Disease
1,575 Citations2002Piet Borst, R. Oude Elferink
This work focuses on three topics: ABC transporters transporting drugs (xenotoxins) and drug conjugates, and a rapidly increasing number of ABC Transporters found to play a role in lipid transport.
New England Journal of MedicineEffect of Aerosolized Recombinant Human DNase on Exacerbations of Respiratory Symptoms and on Pulmonary Function in Patients with Cystic Fibrosis
1,515 Citations1994Henry J. Fuchs, Drucy Borowitz +7 more
In patients with cystic fibrosis, the administration of rhDNase reduced but did not eliminate exacerbations of respiratory symptoms, resulted in slight improvement in pulmonary function, and was well tolerated.
NatureQuorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms
1,509 Citations2000Pradeep K. Singh, Amy L. Schaefer +4 more
ScienceHigh Frequency of Hypermutable <i>Pseudomonas aeruginosa</i> in Cystic Fibrosis Lung Infection
1,468 Citations2000Antonio Oliver, Rafael Cantón +3 more
Determination of spontaneous mutation rates in 128 P. aeruginosa isolates from 30 CF patients revealed that 36% of the patients were colonized by a hypermutable (mutator) strain that persisted for years in most patients, revealing a link between high mutations rates in vivo and the evolution of antibiotic resistance.
New England Journal of MedicineCystic Fibrosis
1,378 Citations2005Steven M. Rowe, Stacey Miller +1 more
From the Gregory Fleming James Cystic Fibrosis Research Center (S.M.R., S.J.S.), University of Alabama at Birmingham, Birmingham.
New England Journal of MedicineIntermittent Administration of Inhaled Tobramycin in Patients with Cystic Fibrosis
1,292 Citations1999Bonnie W. Ramsey, Margaret S. Pepe +10 more
In a 24-week study of patients with cystic fibrosis, intermittent administration of inhaled tobramycin was well tolerated and improved pulmonary function, decreased the density of P. aeruginosa in sputum, and decreased the risk of hospitalization.
CellEvidence for Periciliary Liquid Layer Depletion, Not Abnormal Ion Composition, in the Pathogenesis of Cystic Fibrosis Airways Disease
1,158 Citations1998Hirotoshi Matsui, Barbara R. Grubb +5 more
Data indicate that therapy for CF lung disease should not be directed at modulation of ionic composition, but rather at restoring volume on airway surfaces, as the failure to clear thickened mucus from airways surfaces likely initiates CF airways infection.
Journal of Clinical InvestigationEffects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients
1,110 Citations2002Dieter Worlitzsch, Robert Tarran +13 more
In CF patients with established lung disease, Pseudomonas aeruginosa was located within hypoxic mucopurulent masses in airway lumens, and in vitro studies revealed that CF-specific increases in epithelial O(2) consumption, linked to increased airway surface liquid (ASL) volume absorption and mucus stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial surfaces prior to infection.
ScienceCFTR as a cAMP-Dependent Regulator of Sodium Channels
1,086 Citations1995M. Jackson Stutts, Cecilia M. Canessa +5 more
In CF airway epithelia, the absence of this second function of CFTR as a cAMP-dependent regulator likely accounts for abnormal sodium transport.
Pediatric Pulmonology<i>Pseudomonas aeruginosa</i> and other predictors of mortality and morbidity in young children with cystic fibrosis
1,005 Citations2002Julia Emerson, Margaret Rosenfeld +3 more
A registry‐based study to determine prognostic indicators of 8‐year mortality and morbidity in young children with cystic fibrosis (CF) and clinical outcomes in 1998 is conducted.
JAMAAzithromycin in Patients With Cystic Fibrosis Chronically Infected With Pseudomonas aeruginosa
952 Citations2003Lisa Saiman, Bruce C. Marshall +9 more
Azithromycin treatment was associated with improvement in clinically relevant end points and should be considered for patients with CF who are 6 years or older and chronically infected with P aeruginosa.
The Journal of PediatricsThe changing epidemiology of cystic fibrosis
929 Citations1993Stacey C. FitzSimmons
Overall, patients with cystic fibrosis are living much longer than in the past but still have chronic pulmonary infections and other medical complications related to their disease, including diabetes, intestinal obstruction, cirrhosis, hemoptysis, and pneumothorax.
Journal of Clinical InvestigationEffects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients
906 Citations2002Dieter Worlitzsch, Robert Tarran +13 more
Nature MedicineIncreased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice
899 Citations2004Marcus Mall, Barbara R. Grubb +3 more
It is concluded that increasing airway Na+ absorption initiates cystic fibrosis-like lung disease and produces a model for the study of the pathogenesis and therapy of this disease.
The LancetCystic fibrosis
884 Citations2003Félix Ratjen, Gerd Döring
Advances in understanding and treatment of cystic fibrosis are summarized, focusing on pulmonary disease, which accounts for most morbidity and deaths.
New England Journal of MedicineA Controlled Trial of Long-Term Inhaled Hypertonic Saline in Patients with Cystic Fibrosis
860 Citations2006Mark R. Elkins, Michael Robinson +7 more
Hypertonic saline preceded by a bronchodilator is an inexpensive, safe, and effective additional therapy for patients with cystic fibrosis.
American Journal of EpidemiologyPredictive 5-Year Survivorship Model of Cystic Fibrosis
752 Citations2001Theodore G. Liou, Frederick R. Adler +4 more
A validated 5-year survivorship model is created that provides insights into the complex nature of cystic fibrosis and supplies a rigorous tool for clinical practice and research.
New England Journal of MedicineEffect of High-Dose Ibuprofen in Patients with Cystic Fibrosis
737 Citations1995Michael W. Konstan, Pamela J. Byard +2 more
In patients with cystic fibrosis and mild lung disease, high-dose ibuprofen, taken consistently for four years, significantly slows the progression of the lung disease without serious adverse effects.
New England Journal of MedicineMucus Clearance and Lung Function in Cystic Fibrosis with Hypertonic Saline
679 Citations2006Scott H. Donaldson, William D. Bennett +4 more
In patients with cystic fibrosis, inhalation of hypertonic saline produced a sustained acceleration of mucus clearance and improved lung function, and in vitro data suggested that sustained hydration of airway surfaces was responsible for the sustained improvement in mucus clearing.
Nature GeneticsSubmucosal glands are the predominant site of CFTR expression in the human bronchus
649 Citations1992John F. Engelhardt, James R. Yankaskas +6 more
The data suggest mechanisms whereby defects in CFTR expression could lead to abnormal production of mucus in human lung, particularly in non–CF individuals.
European Respiratory JournalAntibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus
617 Citations2000Gerd Döring, S.P. Conway +5 more
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, and the design of future antibiotic studies in the context of Pseudomonas aeruginosa lung infection in cystic fibrosis patients were recommended.
American Journal of Respiratory and Critical Care MedicineImprovement of Survival in Patients with Diffuse Panbronchiolitis Treated with Low-dose Erythromycin
579 Citations1998Shoji Kudoh, Arata Azuma +3 more
The efficacy of EM treatment increased the survival rate of patients with DPB, which was more significant in the older than in the younger patients, and a significant difference in the survival rates between the two subgroups in Group c (p < 0.001).
CHEST JournalCystic Fibrosis Adult Care
577 Citations2004James R. Yankaskas, Bruce C. Marshall +3 more
This work aims to provide a standard of care for cystic fibrosis patients with at-risk children in the United States using a simple, scalable, and scalable approach that reduces uncertainty and uncertainty about the severity of the disease.
New England Journal of MedicineCorrelation between Genotype and Phenotype in Patients with Cystic Fibrosis
564 Citations1993The Cystic Fibrosis Genotype-Phenotype Consortium
ScienceCurcumin, a Major Constituent of Turmeric, Corrects Cystic Fibrosis Defects
561 Citations2004Marie E. Egan, Marilyn Pearson +8 more
Curcumin treatment may be able to correct defects associated with the homozygous expression of ΔF508 CFTR, which results in the production of a misfolded CFTR protein that is retained in the endoplasmic reticulum and targeted for degradation.
The LancetLong term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial
546 Citations2002A Equi, IM Balfour-Lynn +2 more
Journal of Clinical InvestigationSmall-molecule correctors of defective F508-CFTR cellular processing identified by high-throughput screening
529 Citations2005Nicoletta Pedemonte
Screening of 150,000 chemically diverse compounds and more than 1,500 analogs of active compounds yielded several classes of DeltaF508-CFTR correctors with micromolar potency that produced greater apical membrane chloride current than did low-temperature rescue.
JAMALongitudinal Development of Mucoid <EMPH>Pseudomonas aeruginosa</EMPH> Infection and Lung Disease Progression in Children With Cystic Fibrosis
519 Citations2005Zhanhai Li
Antibody titers increased with both transitions, but the deterioration in cough scores, chest radiograph scores, and pulmonary function correlated best with transition from nonmucoid to mucoid P aeruginosa.
ThoraxEffect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial
512 Citations2002J. M. Wolter
AZM in adults with CF significantly improved QOL, reduced CRP levels and the number of respiratory exacerbations, and reduced the rate of decline in lung function, suggesting long term AZM may have a significant impact on morbidity and mortality in patients with CF.
Nature MedicineAminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations
496 Citations1996Marybeth Howard, Raymond A. Frizzell +1 more
It is reported that two common, disease–associated stop mutations can be suppressed by treating cells with low doses of the aminoglycoside antibiotic G–418 and treated with gentamicin resulted in the expression of full–length CFTR and restored its cyclic AMP–activated chloride channel activity.
New England Journal of MedicineGenetic Modifiers of Lung Disease in Cystic Fibrosis
495 Citations2005Mitchell L. Drumm, Michael W. Konstan +18 more
Genetic variation in the 5' end of TGFbeta1 or a nearby upstream region modifies disease severity in cystic fibrosis.
New England Journal of MedicineActivation by Extracellular Nucleotides of Chloride Secretion in the Airway Epithelia of Patients with Cystic Fibrosis
494 Citations1991Michael R. Knowles, Lane L. Clarke +1 more
Extracellular nucleotides are effective in vivo chloride secretagogues in the nasal epithelia of patients with cystic fibrosis and the equipotency of ATP and UTP suggests that the effect is mediated by P2 nucleotide receptors.
New England Journal of MedicineGentamicin-Induced Correction of CFTR Function in Patients with Cystic Fibrosis and<i>CFTR</i>Stop Mutations
487 Citations2003Michael Wilschanski, Yaacov Yahav +10 more
In patients with cystic fibrosis who have premature stop codons, gentamicin can cause translational "read through," resulting in the expression of full-length CFTR protein at the apical cell membrane, and thus can correct the typical electrophysiological abnormalities caused by CFTR dysfunction.
The LancetPrevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment
466 Citations1991Niels Henrik Valerius, Christian Koch +1 more
Chronic colonisation with Ps aeruginosa can be prevented in cystic fibrosis by early institution of anti-pseudomonas chemotherapy.
New England Journal of MedicineEfficacy of Aerosolized Tobramycin in Patients with Cystic Fibrosis
455 Citations1993Bonnie W. Ramsey, Henry L. Dorkin +10 more
The short-term aerosol administration of a high dose of tobramycin in patients with clinically stable cystic fibrosis is an efficacious and safe treatment for endobronchial infection with P. aeruginosa.
Journal of Clinical InvestigationAssociation of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis
433 Citations1999Peter Garred, Tacjana Pressler +6 more
Presence of MBL variant alleles is associated with poor prognosis and early death in patients with CF and the predicted age of survival was reduced by 8 years in variant allele carriers when compared with normal homozygotes.
Journal of BacteriologyCystic Fibrosis Sputum Supports Growth and Cues Key Aspects of <i>Pseudomonas aeruginosa</i> Physiology
423 Citations2005Kelli L. Palmer, Lauren M. Mashburn +2 more
It is indicated that CF sputum readily supports high-density P. aeruginosa growth and multiple signals, which reduce swimming motility and prematurely activate the Pseudomonas quinolone signal cell-to-cell signaling cascade in P. Aerug inosa, are present in CF spUTum.
New England Journal of MedicineA Pilot Study of Aerosolized Amiloride for the Treatment of Lung Disease in Cystic Fibrosis
357 Citations1990Michael R. Knowles, Nina L. Church +7 more
It is concluded from this preliminary study that aerosolized amiloride can be safely administered to adults with cystic fibrosis and the slowing of the loss of FVC and the improvement in sputum viscosity and elasticity suggest a beneficial clinical effect.
The Journal of PediatricsA multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis
344 Citations1995Howard Eigen, Beryl J. Rosenstein +2 more
A role for alternate-day prednisone therapy at a dose of 1 mg/kg in patients with mild to moderate cystic fibrosis is suggested, and the benefit of improved lung function appears to outweigh the potential for adverse effects when the treatment period is less than 24 months.
Nature MedicineSuppression of a CFTR premature stop mutation in a bronchial epithelial cell line
334 Citations1997David M. Bedwell, Anisa Kaenjak +7 more
C-418 and gentamicin are also capable of restoring CFTR expression in a CF bronchial epithelial cell line carrying the CFTR W1282X premature stop mutation, based on the reappearance of cAMP-activated chloride currents, the restoration of CFTR protein at the apical plasma membrane, and an increase in the abundance ofCFTR mRNA levels from the W12 82X allele.
Cochrane Database of Systematic ReviewsAntibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis
323 Citations2014Simon C Langton Hewer, Alan R Smyth
Treatment of early Pseudomonas aeruginosa infection with inhaled tobramycin results in microbiological eradication of the organism from respiratory secretions more often than no anti-pseudomonal treatment, and results in clinical improvement after two years.
American Journal of Respiratory and Critical Care MedicineSignificant Microbiological Effect of Inhaled Tobramycin in Young Children with Cystic Fibrosis
316 Citations2003Ronald L. Gibson, Julia Emerson +16 more
It is concluded that 28 days of tobramycin solution for inhalation of 300 mg twice daily is safe and effective for significant reduction of lower airway Pa density in young children with cystic fibrosis.
The LancetALTERNATE-DAY PREDNISONE REDUCES MORBIDITY AND IMPROVES PULMONARY FUNCTION IN CYSTIC FIBROSIS
301 Citations1985HarveyS. Auerbach, J.N.P. Kirkpatrick +2 more
After 4 years, the prednisone-treated group had significant advantages over the placebo group for height, weight, vital capacity, forced expiratory volume in 1 s, peak flow rate, erythrocyte sedimentation rate, and serum IgG.
Journal of Clinical EpidemiologyGender differences in cystic fibrosis: Pseudomonas aeruginosa infection
283 Citations1995Catherine Demko, Pamela J. Byard +1 more
Factors in addition to earlier acquisition of mucoid PA may contribute to the poorer survival of female CF patients, including better percent predicted forced expiratory volume in 1 sec and better survival.
The LancetLong-term azithromycin may improve lung function in children with cystic fibrosis
278 Citations1998Adam Jaffé, J. Francis +2 more
European Respiratory JournalA randomised clinical trial of nebulised tobramycin or colistin in cystic fibrosis
268 Citations2002M.E. Hodson, C. G. Gallagher +1 more
Tobramycin nebuliser solution significantly improved lung function of patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa, but colistin did not, in this study of 1-month's duration.
Journal of Clinical InvestigationExcessive inflammatory response of cystic fibrosis mice to bronchopulmonary infection with Pseudomonas aeruginosa.
265 Citations1997Anna van Heeckeren, Ronald W. Walenga +4 more
The effects of bronchopulmonary infection on mice homozygous for the S489X mutation of the CFTR gene are examined using an animal model of chronic Pseudomonas endobronchial infection to permit examination of the relationship of bacterial infections, inflammation, and the cellular and genetic defects in CF.
Proceedings of the National Academy of SciencesHigh-dose oral <i>N</i> -acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis
254 Citations2006Rabindra Tirouvanziam, C. Conrad +4 more
High-dose oral N-acetylcysteine has the potential to counter the intertwined redox and inflammatory imbalances in CF.
American Journal of Respiratory and Critical Care MedicineEvidence that Systemic Gentamicin Suppresses Premature Stop Mutations in Patients with Cystic Fibrosis
249 Citations2001John P. Clancy, Zsuzsa Bebők +11 more
Gentamicin treatment can suppress premature stop mutations in airway cells from patients with CF, and produce small increases in CFTR Cl(-) conductance (as measured by the nasal PD) in vivo.
Clinical Reviews in Allergy & ImmunologyThe Role of Inflammation in the Pathophysiology of CF Lung Disease
244 Citations2002James F. Chmiel, Melvin Berger +1 more
Development of new anti-inflammatory therapies that impact intracellular signaling pathways and cell-cell communication molecules likely will have the greatest impact on limiting the excessive production of the inflammatory mediators in the CF lung, thereby slowing the decline in lung function and improving survival.
The LancetCombination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial
236 Citations2005Shawn D. Aaron, Katherine L. Vandemheen +21 more
Antibiotic therapy directed by combination antibiotic susceptibility testing did not result in better clinical and bacteriological outcomes compared with Therapy directed by standard culture and sensitivity techniques.
The LancetOnce versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis—the TOPIC study: a randomised controlled trial
225 Citations2005Alan R Smyth, Kelvin H-V Tan +5 more
CHEST JournalNonpharmacologic Airway Clearance Therapies
224 Citations2006F. Dennis McCool, Mark J. Rosen
Some nonpharmacologic protussive therapies are effective in increasing sputum production, but their long-term efficacy in improving outcomes compared with unassisted cough alone is unknown.
Current Opinion in Pulmonary MedicineUpdate on the Burkholderia cepacia complex
217 Citations2005John J. LiPuma
Advances in understanding of Burkholderia cepacia complex infection in cystic fibrosis serve as a critical foundation for further efforts that ultimately will enable better infection control and the development of novel therapeutics to treat Burk holderia cEPacia complex infections in persons with cystic Fibrosis.
The LancetEffect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in patients with cystic fibrosis
217 Citations2001Félix Ratjen, Gerd Döring +1 more
Early antibiotic treatment of airway colonisation with Pseudomonas aeruginosa can delay onset of chronic lung infection in patients with cystic fibrosis and successfully eradication was confirmed by sequential respiratory cultures and serum antibody titres that were negative for P aerugInosa.
ThoraxTGF-beta 1 genotype and accelerated decline in lung function of patients with cystic fibrosis
216 Citations2000Peter D. Arkwright
TGF-β1genotypes may have a role in mediating pulmonary dysfunction in patients with cystic fibrosis and further work is required to determine whether inhibition of TGF- β1 activity in these patients may slow disease progression.
American Journal of Respiratory and Critical Care MedicineA Pilot Study of the Effect of Gentamicin on Nasal Potential Difference Measurements in Cystic Fibrosis Patients Carrying Stop Mutations
208 Citations2000Michael Wilschanski, CHAGIT FAMINI +6 more
Gentamicin may influence the underlying chloride transport abnormality in patients with CF carrying stop mutations and express, in vivo, functional CFTR channels.
Journal of Biological ChemistryC-terminal Truncations Destabilize the Cystic Fibrosis Transmembrane Conductance Regulator without Impairing Its Biogenesis
205 Citations1999Martin Haardt, Mohamed Benharouga +3 more
It is suggested that the C terminus has a central role in maintaining the metabolic stability of the complex-glycosylated CFTR following its exit from the ER and provide a plausible explanation for the severe phenotype of CF patients harboring C-terminal truncations.
Journal of Antimicrobial ChemotherapyPharmacokinetics of inhaled colistin in patients with cystic fibrosis
205 Citations2006Félix Ratjen, E. Rietschel +6 more
The low systemic and high local concentrations of colistin support the use of inhaled Colistin in CF patients infected with P. aeruginosa, according to a multicentre study in 30 patients.
Cochrane Database of Systematic ReviewsChest physiotherapy compared to no chest physiotherapy for cystic fibrosis
189 Citations2015L. Warnock, Alison Gates
The results of this review show that airway clearance techniques have short-term effects in the terms of increasing mucus transport, and no evidence was found on which to draw conclusions concerning the long- term effects.
Pediatric PulmonologyPlacebo-controlled, double-blind, randomized study of aerosolized tobramycin for early treatment ofPseudomonas aeruginosa colonization in cystic fibrosis
189 Citations1998H. G. Wiesemann, Gratiana Steinkamp +5 more
In chronic Pseudomonas aeruginosa pulmonary infection of patients with cystic fibrosis, antibiotic therapy generally fails to eradicate the bacterial pathogen.
Journal of Molecular MedicineAminoglycoside suppression of a premature stop mutation in a Cftr–/– mouse carrying a human CFTR-G542X transgene
180 Citations2002Ming Du, Julie R. Jones +11 more
Results indicate that gentamicin, and to a lesser extent tobramycin, can restore the synthesis of functional hCFTR protein by suppressing the h CFTR-G542X premature stop mutation in vivo.
New England Journal of MedicineRisk of Persistent Growth Impairment after Alternate-Day Prednisone Treatment in Children with Cystic Fibrosis
179 Citations2000Hui-Chuan Lai, Stacey C. FitzSimmons +5 more
Among children with cystic fibrosis who have received alternate-day treatment with prednisone, boys, but not girls, have persistent growth impairment after treatment is discontinued.
American Journal of Respiratory and Critical Care MedicineVentilation Inhomogeneities in Relation to Standard Lung Function in Patients with Cystic Fibrosis
166 Citations2004Richard Kraemer, Andrea Blum +3 more
The study shows that the LCI predicts earlier in life and represented much better functional progression than FEV(1), and there is no single functional predictor of progression in CF, but aside from risk factors, pulmonary hyperinflation, airway obstruction, and ventilation inhomogeneities are important pathophysiologic processes that should be evaluated concomitantly as determinants of lung progression.
American Journal of Respiratory and Critical Care MedicineEffect of Treatment with Dornase Alpha on Airway Inflammation in Patients with Cystic Fibrosis
166 Citations2003K. Paul, Ernst Rietschel +10 more
The LancetComparison of hypertonic saline and alternate-day or daily recombinant human deoxyribonuclease in children with cystic fibrosis: a randomised trial
153 Citations2001Ranjan Suri, Chris Metcalfe +7 more
Hypertonic saline, delivered by jet nebuliser, is not as effective as daily rhDNase, although there is variation in individual response, and there is no evidence of a difference between daily and alternate-day rh DNase.
Nature GeneticsTGFβ signaling in health and disease
151 Citations2004Rosemary J. Akhurst
Inactivating mutations in TGFBR2, encoding the transforming growth factor-β (TGFβ) type 2 receptor, may account for up to 10% of cases of Marfan syndrome, which has implications for a wider spectrum of disorders, including cancer, fibrosis and inflammatory and cardiovascular diseases.
ThoraxContribution of genetic factors other than CFTR to disease severity in cystic fibrosis
148 Citations1998J Hull, Aerin Thomson
The contention that inflammation in cystic fibrosis contributes to tissue damage is supported and isolation of further such factors may lead to identification of patients at risk of more severe disease and allow targeted aggressive therapy in this group.
American Journal of Respiratory and Critical Care MedicineMulticenter Randomized Controlled Trial of Withdrawal of Inhaled Corticosteroids in Cystic Fibrosis
147 Citations2006Ian M. Balfour‐Lynn, Belinda Lees +5 more
In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids and potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings.
CHEST JournalEffects of 12-Week Administration of Dornase Alfa in Patients with Advanced Cystic Fibrosis Lung Disease
146 Citations1996Karen McCoy, Scott Hamilton +1 more
Pulmonary function as measured by FEV 1 and FVC improved significantly in the dornase alfa-treated patients and was found to be safe and well tolerated over the 12-week study period.
Cochrane Database of Systematic ReviewsInhaled corticosteroids for cystic fibrosis
144 Citations2016Ian M. Balfour‐Lynn, Karen Welch
Evidence is insufficient to establish whether inhaled corticosteroids are beneficial in cystic fibrosis, but withdrawal in those already taking them has been shown to be safe, and there is some evidence they may cause harm in terms of growth.
American Journal of Respiratory and Critical Care MedicineImpact of <i>Burkholderia dolosa</i> on Lung Function and Survival in Cystic Fibrosis
143 Citations2005Leslie A. Kalish, David A. Waltz +6 more
Characterization of impact of B. dolosa chronic infection in cystic fibrosis is associated with accelerated loss of lung function and decreased survival.
Proceedings of the National Academy of SciencesEvolving stealth: Genetic adaptation of <i>Pseudomonas aeruginosa</i> during cystic fibrosis infections
142 Citations2006Dao Nguyen, Pradeep K. Singh
The innovative work by Smith et al .
Pflügers Archiv - European Journal of PhysiologyDirect action of genistein on CFTR
139 Citations1997Frank Weinreich, Phillip G. Wood +2 more
A direct interaction of genistein with CFTR, probably at a nucleotide binding site, which leads to a higher open probability ofGenistein-mediated potentiation in excised patches is independent of protein phosphatase activity, as it is readily reversible, even after complete inhibition of protein kinase A activity.
The Journal of PediatricsInduced sputum inflammatory measures correlate with lung function in children with cystic fibrosis
135 Citations2002Scott D. Sagel, Marci K. Sontag +4 more
It is concluded that measures of inflammation in induced sputum correlate with FEV(1) in clinically stable children with CF with normal to mildly abnormal lung function and that they may be useful as surrogate outcome measures in clinical trials.
Cochrane Database of Systematic ReviewsOnce-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis
129 Citations2017Alan R Smyth, Jayesh Bhatt +1 more
Once- and three-times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis.
American Journal of Physiology-Cell PhysiologyUTP inhibits Na<sup>+</sup> absorption in wild-type and ΔF508 CFTR-expressing human bronchial epithelia
128 Citations1999Daniel C. Devor, Joseph M. Pilewski
It is concluded that increasing cellular Ca2+ induces a long-term inhibition of transepithelial Na+transport across normal and CF HBE at least partly due to downregulation of a basolateral membrane K+ conductance.
Current Opinion in Pulmonary MedicinePseudomonas acquisition in young patients with cystic fibrosis: pathophysiology, diagnosis, and management
120 Citations2003Margaret Rosenfeld, Bonnie W. Ramsey +1 more
There is a critical need for further investigation of the clinical outcomes associated with early intervention, the long-term safety profile, and the optimal drug regimen for early Pa infection in CF patients.
Journal of Biological ChemistryEvidence against the Rescue of Defective ΔF508-CFTR Cellular Processing by Curcumin in Cell Culture and Mouse Models
113 Citations2004Yuanlin Song, N.D. Sonawane +5 more
Assay of serum curcumin by ethyl acetate extraction followed by liquid chromatography/mass spectrometry indicated a maximum serum concentration of 60 nm, well below that of 5–15 μm, where cellular effects by sarcoplasmic/endoplasmIC reticulum calcium pump inhibition are proposed to occur.
American Journal of Respiratory Cell and Molecular BiologyLung Inflammation as a Therapeutic Target in Cystic Fibrosis
110 Citations2004David R. Koehler, Gregory P. Downey +3 more
The mechanisms responsible for inflammation in the CF lung are examined, potential therapeutic strategies targeting inflammation are discussed, and potential therapeutic strategy targeting inflammation is discussed.
CHEST JournalDornase Alfa Reduces Air Trapping in Children With Mild Cystic Fibrosis Lung Disease
103 Citations2005Terry E. Robinson, Michael L. Goris +5 more
Quantitative air trapping is a more consistent sensitive outcome measure than either spirometry or total HRCT scores, and can discriminate differences in treatment effects in children with minimal CF lung disease.
Journal of Pharmacology and Experimental TherapeuticsEvaluation of Second Generation Amiloride Analogs as Therapy for Cystic Fibrosis Lung Disease
95 Citations2004Andrew J. Hirsh, Juan Sabater +6 more
The hypothesis that ENaC blocker aerosol therapy increases MC is supported, however, rapid absorption of benzamil from the mucosal surface offset its greater potency, making it equieffective with amiloride in vivo.
CHEST JournalThe Use of Anti-inflammatory Medications in Cystic Fibrosis
94 Citations1999Christopher M. Oermann, Marianna Sockrider +1 more
Anti-inflammatory medications appear to be an underutilized therapeutic modality in CF care, true for numbers of patients receiving these drugs as well as numbers of care providers prescribing them.
Cochrane Database of Systematic ReviewsChest physiotherapy compared to no chest physiotherapy for cystic fibrosis
92 Citations2000Cees P. van der Schans, Ammani Prasad +1 more
Pediatric PulmonologySafety and tolerability of denufosol tetrasodium inhalation solution, a novel P2Y<sub>2</sub> receptor agonist: Results of a phase 1/phase 2 multicenter study in mild to moderate cystic fibrosis
90 Citations2005Robin R. Deterding, George Retsch‐Bogart +13 more
D doses up to 60 mg of denufosol inhalation solution were well‐tolerated in most subjects, and may enhance mucociliary clearance for a longer period of time than previously investigated P2Y2 agonists.
Biochemical JournalNovel molecular approaches to cystic fibrosis gene therapy
90 Citations2005Tim W. R. LEE, David A. Matthews +1 more
This review of approaches to cystic fibrosis gene therapy covers these areas in detail and highlights recent progress in the field, with increasing evidence to suggest that additional ligands that facilitate endosomal escape or contain a nuclear localization signal may enhance liposome-mediated gene delivery.
CHEST JournalBronchial Constriction and Inhaled Colistin in Cystic Fibrosis
89 Citations2005Ghassan A. Alothman, Bernard Ho +5 more
The results demonstrated that colistin can cause bronchospasm, particularly in those patients with coexisting CF and asthma.
Journal of Antimicrobial ChemotherapyAdaptive resistance to tobramycin in <i>Pseudomonas aeruginosa</i> lung infection in cystic fibrosis
88 Citations1996Murray L. Barclay, Evan J. Begg +4 more
The presence and time course of adaptive resistance in humans may have implications for improving aminoglycoside dosing regimens.
Journal of Aerosol MedicineHyperosmolar Agents and Clearance of Mucus in the Diseased Airway
87 Citations2006Evangelia Daviskas, Sandra D. Anderson
Clinical studies have demonstrated that hypertonic saline and mannitol increase clearance of mucus acutely in patients with mild asthma, bronchiectasis, and cystic fibrosis and that inhalation of 7% HS twice daily over 12 months showed similar results to the short-term studies without a change in the bacterial load in CF patients.
ThoraxElective versus symptomatic antibiotic treatment in cystic fibrosis patients with chronic Pseudomonas infection of the lungs
84 Citations2000J.S. Elborn
This study did not demonstrate an advantage of a policy of elective antibiotic treatment over symptomatic treatment in patients with cystic fibrosis chronically infected with Pseudomonasspecies.
CHEST JournalThe Efficacy and Safety of Meropenem and Tobramycin vs Ceftazidime and Tobramycin in the Treatment of Acute Pulmonary Exacerbations in Patients With Cystic Fibrosis
84 Citations2005Jeffrey L. Blumer, Lisa Saiman +2 more
Therapy with both meropenem/tobramycin and ceftazidime-resistant P aeruginosa improved pulmonary and clinical status and reduced sputum bacterial burden in CF patients with APEs.
Journal of Pharmacology and Experimental TherapeuticsEffect of Ibuprofen on Neutrophil Migration in Vivo in Cystic Fibrosis and Healthy Subjects
82 Citations2003Michael W. Konstan, Jeanne E. Krenicky +6 more
It is suggested that Cmax >50 μg/ml and twice daily dosing of ib uprofen are required to decrease PMN migration, and the current recommendation that pharmacokinetics should be performed in CF patients prescribed ibuprofen is reinforced.
American Journal of Respiratory and Critical Care MedicineEffects of Segregation on an Epidemic <i>Pseudomonas aeruginosa</i> Strain in a Cystic Fibrosis Clinic
82 Citations2005Amanda Griffiths, Kris M. Jamsen +6 more
Successful infection control measures provided additional indirect evidence for person-to-person transmission of an epidemic strain within the clinic and further studies are needed to resolve whether cohort segregation completely eliminates cross-infection.
Advanced Drug Delivery ReviewsInhaled P2Y2 receptor agonists as a treatment for patients with Cystic Fibrosis lung disease
78 Citations2002Don Kellerman, Richard Evans +2 more
Results of preclinical research suggest that P2Y(2) receptor agonists inhibit sodium absorption, restore chloride conductance and rehydrate the CF airway surface.
American Journal of Respiratory and Critical Care MedicineHeterogeneity of Treatment Response to Azithromycin in Patients with Cystic Fibrosis
76 Citations2005Lisa Saiman, Nicole Mayer-Hamblett +2 more
Subgroup analyses demonstrated that overall, participants on long-term aerosolized tobramycin and/or rhDNase had worse baseline lung function, but still benefited from azithromycin, as evidenced by a lower risk of exacerbations.
…