Inhaled mannitol for cystic fibrosis.
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ABSTRACT:
SUBMITTER: Nevitt SJ
PROVIDER: S-EPMC7195814 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Cystic Fibrosis (CF), one of the most frequent genetic diseases, is characterized by the production of viscous mucus in several organs. In the lungs, mucus clogs the airways and traps bacteria, leading to recurrent/resistant infections and lung damage. For cystic fibrosis patients, respiratory failure is still lethal in early adulthood since available treatments display incomplete efficacy. OBJECTIVE:The objective of this review is to extend the current knowledge in the field of available treatments for cystic fibrosis. A special focus has been given to inhaled peptide-based drugs. METHODS:The current review is based on recent and/or relevant literature and patents already available in various scientific databases, which include PubMed, PubMed Central, Patentscope and Science Direct. The information obtained through these diverse databases is compiled, critically interpreted and presented in the current study. An in-depth but not systematic approach to the specific research question has been adopted. RESULTS:Recently, peptides have been proposed as possible pharmacologic agents for the treatment of respiratory diseases. Of note, peptides are suitable to be administered by inhalation to maximize efficacy and reduce systemic side effects. Moreover, innovative delivery carriers have been developed for drug administration through inhalation, allowing not only protection against proteolysis, but also a prolonged and controlled release. CONCLUSION:Here, we summarize newly patented peptides that have been developed in the last few years and advanced technologies for inhaled drug delivery to treat cystic fibrosis.
| S-EPMC6751348 | biostudies-literature
Project description:BACKGROUND:Inhaled alpha1-proteinase inhibitor (PI) is known to reduce neutrophil elastase burden in some patients with CF. This phase 2a study was designed to test inhaled Alpha-1 HC, a new aerosolized alpha1-PI formulation, in CF patients. METHODS:We performed a randomized, double-blind, placebo-controlled study and evaluated the safety of 100 or 200mg of inhaled Alpha-1 HC once daily for 3 weeks in subjects with CF. Thirty adult subjects were randomized in a 2:1 ratio to receive Alpha-1 HC or placebo. RESULTS:Drug delivery was confirmed by a dose-dependent increase in the sputum alpha1-PI. Seven (20.0%) of the 35 adverse events in the 100-mg dose group, 3 (13.0%) of 23 in the 200-mg dose group, and 4 (14.3%) of 28 in the placebo group were drug-related in these subjects. One serious adverse event occurred in 1 subject within each group. CONCLUSIONS:Alpha-1 HC inhalation was safe and well tolerated.
| S-EPMC4993024 | biostudies-literature
Project description:Tobramycin powder for inhalation (TOBI Podhaler or TIP) is approved for the treatment of Pseudomonas aeruginosa airway infection in patients with cystic fibrosis (CF). A population pharmacokinetic model for tobramycin inhalation powder (TIP) in CF patients was developed to characterize the effect of covariates including body mass index (BMI) and lung function (forced expiratory volume in 1 s as percent of the predicted value (FEV1% predicted) at baseline) on the serum exposure parameters.A two-compartment model with first-order elimination and first-order absorption was developed. Across a range of baseline demographic values in the study population, the predicted mean values for the maximum (Cmax) and trough (Ctrough) plasma concentrations at steady state were at least 7.5 and 5-fold lower, respectively, than the recommended thresholds for tobramycin toxicity (12 µg/ml for Cmax and 2 µg/ml for Ctrough). This model adequately described the tobramycin serum concentration-time course in CF patients following inhalation of TIP. The results indicate that no BMI- or FEV1-based dose adjustment is needed for use of TIP in CF patients.
| S-EPMC3944114 | biostudies-literature
Project description:RationaleThe effectiveness and safety of aztreonam lysine for inhalation (AZLI) in patients with cystic fibrosis (CF) on maintenance treatment for Pseudomonas aeruginosa (PA) airway infection was evaluated in this randomized, double-blind, placebo-controlled study.ObjectivesTo evaluate the safety and efficacy of inhaled aztreonam lysine in controlling PA infection in patients with CF.MethodsAfter randomization and a 28-day course of tobramycin inhalation solution (TIS), patients (n = 211; > or =6 yr; > or =3 TIS courses within previous year; FEV(1) > or = 25% and < or =75% predicted values) were treated with 75 mg AZLI or placebo, twice or three times daily for 28 days, then monitored for 56 days. The primary efficacy endpoint was time to need for additional inhaled or intravenous antipseudomonal antibiotics. Secondary endpoints included changes in respiratory symptoms (CF Questionnaire-Revised [CFQ-R] Respiratory Scale), pulmonary function (FEV(1)), and sputum PA density. Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored.Measurements and main resultsAZLI treatment increased median time to need for additional antipseudomonal antibiotics for symptoms of pulmonary exacerbation by 21 days, compared with placebo (AZLI, 92 d; placebo, 71 d; P = 0.007). AZLI improved mean CFQ-R respiratory scores (5.01 points, P = 0.02), FEV(1) (6.3%, P = 0.001), and sputum PA density (-0.66 log(10) cfu/g, P = 0.006) compared with placebo; no AZLI dose-response was observed. Adverse events reported for AZLI and placebo were comparable and consistent with CF lung disease. Susceptibility of PA to aztreonam at baseline and end of therapy were similar.ConclusionsAZLI was effective in patients with CF using frequent TIS therapy. AZLI delayed time to need for inhaled or intravenous antipseudomonal antibiotics, improved respiratory symptoms and pulmonary function, and was well tolerated. Clinical trial registered with www.clinicaltrials.gov (NCT 00104520).
| S-EPMC2577727 | biostudies-literature
Project description: Not available
| S-EPMC8407188 | biostudies-literature
Project description:This multi-center study will compare multi-target DNA and quantitative FIT stool-based testing to colonoscopy in individuals with Cystic Fibrosis (CF) undergoing colon cancer screening with colonoscopy. The primary endpoint is detection of any adenomas, including advanced adenomas and colorectal cancer (CRC).
| 2726863 | ecrin-mdr-crc
Project description:Patients with cystic fibrosis (CF) experience frequent pulmonary exacerbations (PExs). Clinicians manage these episodes of worsening signs and symptoms in a variety of ways.To characterize the antibiotic management and associated change in lung function following PExs.We used 2003-2005 data from the Epidemiologic Study of Cystic Fibrosis to examine antibiotic treatment and the immediate and long-term lung function change associated with clinician reported PExs.A total of 45,374 PExs were reported in 13,194 unique patients. Most PExs (73%) were treated with oral antibiotics, while 39% were treated IV and 24% were treated with inhaled antibiotics. The likelihood of non-IV versus IV antibiotic treatment was associated with the patient's age, stage of lung disease, and magnitude of lung function drop prior to the PEx. Following treatment, the average improvement in the FEV1 was 3.4 ± 12.2% predicted with a greater (5.1 ± 12.7% predicted) improvement following IV antibiotic treatment than with non-IV treatment (2.0 ± 11.6% predicted). When the best FEV1 from the year before was compared with 180 days following the PEx there was an average fall of 3.8 ± 10.5% predicted with little difference observed between antibiotic treatment routes. Patients with only one exacerbation during the 3-year study had a similar loss of lung function to patients with no reported exacerbations.Clinicians treat the majority of PExs with oral antibiotics, particularly in younger, healthier patients. Pulmonary function improves with antibiotic therapy, however, PExs are associated with lung function deterioration over time.
| S-EPMC4049300 | biostudies-literature
Project description:We assessed the short-term efficacy and safety of aztreonam lysine for inhalation (AZLI [an aerosolized monobactam antibiotic]) in patients with cystic fibrosis (CF) and Pseudomonas aeruginosa (PA) airway infection.In this randomized, double-blind, placebo-controlled, international study (AIR-CF1 trial; June 2005 to April 2007), patients (n = 164; >or= 6 years of age) with FEV(1) >or= 25% and <or= 75% predicted values, and no recent use of antipseudomonal antibiotics or azithromycin were treated with 75 mg of AZLI (three times daily for 28 days) or placebo (1:1 randomization), then were monitored for 14 days after study drug completion. The primary efficacy end point was change in patient-reported respiratory symptoms (CF-Questionnaire-Revised [CFQ-R] Respiratory Scale). Secondary end points included changes in pulmonary function (FEV(1)), sputum PA density, and nonrespiratory CFQ-R scales. Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored.After 28 days of treatment, AZLI improved the mean CFQ-R respiratory score (9.7 points; p < 0.001), FEV(1) (10.3% predicted; p < 0.001), and sputum PA density (- 1.453 log(10) cfu/g; p < 0.001), compared with placebo. Significant improvements in Eating, Emotional Functioning, Health Perceptions, Physical Functioning, Role Limitation/School Performance, and Vitality CFQ-R scales were observed. Adverse events were consistent with symptoms of CF lung disease and were comparable for AZLI and placebo except the incidence of "productive cough" was reduced by half in AZLI-treated patients. PA aztreonam susceptibility at baseline and end of therapy were similar.In patients with CF, PA airway infection, moderate-to-severe lung disease, and no recent use of antipseudomonal antibiotics or azithromycin, 28-day treatment with AZLI significantly improved respiratory symptoms and pulmonary function, and was well tolerated.Clinicaltrials.gov Identifier: NCT00112359.
| S-EPMC2818415 | biostudies-literature
Project description:Pulmonary infections caused by Pseudomonas aeruginosa (PA) represent the leading cause of pulmonary morbidity in adults with cystic fibrosis (CF). In addition to tobramycin, colistin, and aztreonam, levofloxacin has been approved in Europe to treat PA infections. Nevertheless, no lung deposition data on inhaled levofloxacin are yet available. We conducted a Functional Respiratory Imaging (FRI) study to predict the lung deposition of levofloxacin in the lungs of patients with CF. Three-dimensional airway models were digitally reconstructed from twenty high-resolution computed tomography scans obtained from historical patients' records. Levofloxacin aerosols generated with the corresponding approved nebuliser were characterised according to pharmacopeia. The obtained data were used to inform a computational fluid dynamics simulation of levofloxacin lung deposition using breathing patterns averaged from actual CF patients' spirometry data. Levofloxacin deposition in the lung periphery was significantly reduced by breathing patterns with low inspiratory times and high inspiratory flow rates. The intrathoracic levofloxacin deposition percentages for moderate and mild CF lungs were, respectively, 37.0% ± 13.6 and 39.5% ± 12.9 of the nominal dose. A significant albeit modest correlation was found between the central-to-peripheral deposition (C/P) ratio of levofloxacin and FEV1. FRI analysis also detected structural differences between mild and moderate CF airways. FRI revealed a significant intrathoracic deposition of levofloxacin aerosols, which distributed preferentially to the lower lung lobes, with an influence of the deterioration of FEV1 on the C/P ratio. The three-dimensional rendering of CF airways also detected structural differences between the airways of patients with mild and moderate CF.
| S-EPMC8708197 | biostudies-literature
Project description:IntroductionPrevalence of fungi has been rising in the cystic fibrosis (CF) population. Scedosporium species (spp) is the second most common mold seen in the CF respiratory tract. However, the characteristics associated with Scedosporium isolation and its clinical implications are poorly understood. The goal of this study was to determine clinical factors associated with Scedosporium spp to better understand the mechanisms that may contribute to the emergence of filamentous fungi in CF.MethodsWe conducted a retrospective cohort study of subjects followed in the CF Foundation Patient Registry between January 1, 2010 and December 31, 2012. Patients under 6 years of age, history of solid organ transplantation, and insufficient respiratory culture data were excluded. We used a multivariable logistic regression model to determine demographic data and baseline disease characteristics, medications and co-infections associated with Scedosporium spp recovery in CF sputum.ResultsAmong 19 023 subjects, prevalence of Scedosporium spp was 615 (3.2%). Older age (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.07, 1.26) and white race (OR 1.69, 95% CI 1.09, 2.63) were the demographic factors associated with Scedosporium spp isolation. Inhaled antibiotic use had a significant association with Scedosporium isolation (OR 2.01, 95% CI 1.61, 2.52). For every additional course of intravenous antibiotics, the odds of Scedosporium isolation increased by 8% (OR 1.08, 95% CI 1.03, 1.14).ConclusionsThe association between inhaled antibiotics and Scedosporium informs us that chronic inhaled antibiotics may be playing a role in Scedosporium isolation. Further investigation to better characterize this relationship is necessary.
| S-EPMC8115015 | biostudies-literature