Clinical use of Ibuprofen is associated with slower FEV1 decline in children with cystic fibrosis.
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ABSTRACT: Rationale
High-dose ibuprofen in a 4-year controlled trial slowed FEV(1) decline in young subjects with cystic fibrosis, but the effectiveness of ibuprofen has not been assessed in a large group of patients treated clinically with this therapy.Objectives
To assess the effect of ibuprofen therapy on FEV(1) decline in children and adolescents with cystic fibrosis, using observational data from the Cystic Fibrosis Foundation Patient Registry.Methods
The rate of decline in FEV(1) percent predicted over 2-7 years among patients age 6-17 years with FEV(1) > 60% predicted, and who were treated with ibuprofen (1,365), was compared with patients of similar age and disease severity who were not treated with this therapy (8,960). Multilevel repeated-measures mixed-regression models were used to estimate rates of decline, adjusting for characteristics and therapies that influenced FEV(1) decline. Adverse effects were compared among those treated versus not treated with ibuprofen.Measurements and main results
FEV(1) declined less rapidly among patients treated with ibuprofen (difference, 0.60% predicted per year; 95% confidence interval, 0.31 to 0.89; P < 0.0001); a 29% reduction in slope based on an average decline of 2.08% predicted per year for patients not treated. Those treated with ibuprofen were more likely to have an episode of gastrointestinal bleeding requiring hospitalization, but the occurrence was rare in both groups (annual incidence, 0.37 vs. 0.14%; relative risk, 2.72; P < 0.001).Conclusions
Slower rates of FEV(1) decline are seen in children and adolescents with cystic fibrosis who are treated with ibuprofen. The apparent benefits of ibuprofen therapy outweigh the small risk of gastrointestinal bleeding.
SUBMITTER: Konstan MW
PROVIDER: S-EPMC2176097 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Clinical trials have demonstrated the benefits of ibuprofen therapy in cystic fibrosis (CF) patients, an effect that is currently attributed to ibuprofen's anti-inflammatory properties. Yet, a few previous reports demonstrated an antimicrobial activity of ibuprofen as well, although none investigated its direct effects on the pathogens found in the CF lung, which is the focus of this work. Determination of ibuprofen's in vitro antimicrobial activity against Pseudomonas aeruginosa and Burkholderia species strains through measurements of the endpoint number of CFU and growth kinetics showed that ibuprofen reduced the growth rate and bacterial burden of the tested strains in a dose-dependent fashion. In an in vitroPseudomonas biofilm model, a reduction in the rate of biomass accumulation over 8 h of growth with ibuprofen treatment was observed. Next, an acute Pseudomonas pneumonia model was used to test this antimicrobial activity after the oral delivery of ibuprofen. Following intranasal inoculation, ibuprofen-treated mice exhibited lower CFU counts and improved survival compared with the control animals. Preliminary biodistribution studies performed after the delivery of ibuprofen to mice by aerosol demonstrated a rapid accumulation of ibuprofen in serum and minimum retention in lung tissue and bronchoalveolar lavage fluid. Therefore, ibuprofen-encapsulated polymeric nanoparticles (Ibu-NPs) were formulated to improve the pharmacokinetic profile. Ibu-NPs formulated for aerosol delivery inhibited the growth of P. aeruginosa in vitro and may provide a convenient dosing method. These results provide an additional explanation for the previously observed therapeutic effects of ibuprofen in CF patients and further strengthen the argument for its use by these patients.
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Project description:BackgroundComplications from liver cirrhosis are a leading cause of death in children with cystic fibrosis. Identifying children at risk for developing liver cirrhosis and halting its progression are critical to reducing liver-associated mortality.ObjectiveQuantitative US imaging, such as shear-wave elastography (SWE), might improve the detection of liver fibrosis in children with cystic fibrosis (CF) over gray-scale US alone. We incorporated SWE in our pediatric CF liver disease screening program and evaluated its performance using magnetic resonance (MR) elastography.Materials and methodsNinety-four children and adolescents with CF underwent 178 SWE exams, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and platelet measurements. Of these, 27 children underwent 34 MR elastography exams. We evaluated SWE performance using 6-MHz and 9-MHZ point SWE, and 9-MHz two-dimensional (2-D) SWE.ResultsThe 6-MHz point SWE was the only method that correlated with MR elastography (r=0.52; 95% confidence interval [CI] 0.20-0.74; P=0.003). SWE of 1.45 m/s distinguished normal from abnormal MR elastography (79% sensitivity, 100% specificity, 100% positive predictive value [PPV], 55% negative predictive value [NPV], area under the receiver operating characteristic [AUROC] curve 0.94). SWE of 1.84 m/s separated mild-moderate (3.00-4.77 kPa) from severe (>4.77 kPa) MR elastography (88% sensitivity, 86% specificity, 78% PPV, 93% NPV, AUROC 0.79). Elevations of AST, ALT, GGT and thrombocytopenia were associated with higher SWE. AST-to-platelet ratio index of 0.42, fibrosis-4 of 0.29, and GGT-to-platelet ratio of 1.43 all had >95% NPV for SWE >1.84 m/s.ConclusionGiven its correlation with MR elastography, SWE might be a clinically useful predictor of liver fibrosis. We identified imaging criteria delineating the use of SWE to identify increased liver stiffness in children with CF. With multicenter validation, these data might be used to improve the detection and monitoring of liver fibrosis in children with CF.
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