Cellular Redox State Acts as Switch to Determine the Direction of NNT-Catalyzed Reaction in Cystic Fibrosis Cells.

Int J Mol Sci. 2021 Jan 19;22(2):

Authors: Favia M, Atlante A

Abstract
The redox states of NAD and NADP are linked to each other in the mitochondria thanks to the enzyme nicotinamide nucleotide transhydrogenase (NNT) which, by utilizing the mitochondrial membrane potential (mΔΨ), catalyzes the transfer of redox potential between these two coenzymes, reducing one at the expense of the oxidation of the other. In order to define NNT reaction direction in CF cells, NNT activity under different redox states of cell has been investigated. Using spectrophotometric and western blotting techniques, the presence, abundance and activity level of NNT were determined. In parallel, the levels of NADPH and NADH as well as of mitochondrial and cellular ROS were also quantified. CF cells showed a 70% increase in protein expression compared to the Wt sample; however, regarding NNT activity, it was surprisingly lower in CF cells than healthy cells (about 30%). The cellular redox state, together with the low mΔΨ, pushes to drive NNT reverse reaction, at the expense of its antioxidant potential, thus consuming NADPH to support NADH production. At the same time, the reduced NNT activity prevents the NADH, produced by the reaction, from causing an explosion of ROS by the damaged respiratory chain, in accordance with the reduced level of mitochondrial ROS in NNT-loss cells. This new information on cellular bioenergetics represents an important building block for further understanding the molecular mechanisms responsible for cellular dysfunction in cystic fibrosis.

PMID: 33478087 [PubMed - in process]

Microstructured Lipid Carriers (MLC) Based on N-Acetylcysteine and Chitosan Preventing Pseudomonas aeruginosa Biofilm.

Int J Mol Sci. 2021 Jan 17;22(2):

Authors: Guerini M, Grisoli P, Pane C, Perugini P

Abstract
The aim of this work was the development of microstructured lipid carriers (MLC) based on chitosan (CH) and containing N-acetylcysteine (NAC), a mucolytic and antioxidant agent, to inhibit the formation of Pseudomonas aeruginosa biofilm. MLC were prepared using the high shear homogenization technique. The MLC were characterized for morphology, particle size, Z potential, encapsulation efficiency and drug release. The antioxidant properties of NAC-loaded microstructured carriers were evaluated through an in vitro spectrophotometer assay. Finally, the activity of NAC-CH-MLC on biofilm production by Pseudomonas aeruginosa was also evaluated. Results obtained from this study highlighted that the use of chitosan into the inner aqueous phase permitted to obtain microstructured particles with a narrow size range and with good encapsulation efficiency. NAC-loaded MLC showed higher antioxidant activity than the free molecule, demonstrating how encapsulation increases the antioxidant effect of the molecule. Furthermore, the reduction of biofilm growth resulted extremely high with MLC being 64.74% ± 6.2% and 83.74% ± 9.95%, respectively, at 0.5 mg/mL and 2 mg/mL. In conclusion, this work represents a favorable technological strategy against diseases in which bacterial biofilm is relevant, such as cystic fibrosis.

PMID: 33477393 [PubMed - in process]

The PROSPECT Is Bright for CFTR Modulators.

Ann Am Thorac Soc. 2021 01;18(1):32-33

Authors: Montemayor K, Lechtzin N

PMID: 33385230 [PubMed - indexed for MEDLINE]

From micro to macro; joining the dots of early CF lung disease.

J Cyst Fibros. 2020 11;19(6):850-851

Authors:

PMID: 32917548 [PubMed - indexed for MEDLINE]

New therapies for people with CF in the CFTR modulator world.

J Cyst Fibros. 2020 09;19(5):669-670

Authors: Wainwright CE

PMID: 32792265 [PubMed - indexed for MEDLINE]

[Clinical characteristics and gene variants of patients with infantile intrahepatic cholestasis].

Zhongguo Dang Dai Er Ke Za Zhi. 2021 Jan;23(1):91-97

Authors: Wang MJ, Zhong XM, Ma X, Ning HJ, Zhu D, Gong YZ, Jin M

Abstract
OBJECTIVE: To explore the clinical characteristics and genetic findings of patients with infantile intrahepatic cholestasis.
METHODS: The clinical data were collected in children who were admitted to the Department of Gastroenterology in Children's Hospital, Capital Institute of Pediatrics from June 2017 to June 2019 and were suspected of inherited metabolic diseases. Next generation sequencing based on target gene panel was used for gene analysis in these children. Sanger sequencing technology was used to verify the genes of the members in this family.
RESULTS: Forty patients were enrolled. Pathogenic gene variants were identified in 13 patients (32%), including SLC25A13 gene variation in 3 patients who were diagnosed with citrin deficiency, JAG1 gene variation in 3 patients who were diagnosed with Alagille syndrome, ABCB11 gene variation in 3 patients who were diagnosed with progressive familial intrahepatic cholestasis type 2, HSD3B7 gene variation in 1 patient who was diagnosed with congenital bile acid synthesis defect type 1, AKR1D1 gene variation in 1 patient who was diagnosed with congenital bile acid synthesis defect type 1, NPC1 gene variation in 1 patient who was diagnosed with Niemann-Pick disease, and CFTR gene variation in 1 patient who was diagnosed with cystic fibrosis.
CONCLUSIONS: The etiology of infantile intrahepatic cholestasis is complex. Next generation sequencing is helpful in the diagnosis of infantile intrahepatic cholestasis.

PMID: 33476544 [PubMed - as supplied by publisher]

Early Life Height Attainment in Cystic Fibrosis Is Associated with Pulmonary Function at Age 6 Years.

Ann Am Thorac Soc. 2021 Jan 21;:

Authors: Sanders DB, Slaven JE, Maguiness K, Chmiel JF, Ren CL

Abstract
RATIONALE: In contrast to the well-described association between early-life weight-for-age, body mass index (BMI) and later lung disease in people with cystic fibrosis (CF), the relationship between height-for-age (HFA) percentiles and respiratory morbidity is not as well-studied. We hypothesized that changes in HFA in children with CF in the first 6 years of life would be associated with pulmonary function at ages 6-7 years.
OBJECTIVE(S): To determine if an association exists between changes in HFA in early life and pulmonary function in school-age children with CF.
METHODS: We performed a retrospective longitudinal cohort study of children with CF followed in the CF Foundation Patient Registry (CFFPR), born between 2003 and 2010, diagnosed before age 2 years, and followed through at least age 7 years. Changes in annualized HFA were classified into mutually exclusive categories. Multivariable ANCOVA models were used to test for an association between forced expiratory volume in 1 second (FEV1) % predicted at age 6-7 years and height trajectory categories.
RESULTS: There were 5,388 eligible children in the CFFPR. The median (IQR) HFA at age 6-7 years was the 39.5th (17.2, 64.9) percentile. The mean (95% CI) FEV1 % predicted at age 6-7 years was 95.6 (95.1, 96.1). In a multivariable regression model, mean (95% CI) FEV1 % predicted was higher for children with HFA always above the 50th percentile [97.8 (96.3, 99.4)], compared to children whose height increased ≥10 percentile points, [95.1 (93.7, 96.6)], was stable, [94.3 (92.8, 95.7)], or decreased ≥10 percentile points, [95.7 (94.2, 97.3)]. The association between HFA categories and FEV1 % predicted was not affected by adding mean annualized BMI percentile at age 6-7 years to the regression model. Among those with HFA that decreased ≥10 percentile points, there was a correlation between the nadir annualized HFA percentile and FEV1 % predicted at age 6-7 years.
CONCLUSIONS: Children with CF with HFA always above the 50th percentile have the highest pulmonary function at age 6-7 years. Maintaining BMI >50th percentile remains an important achievable goal for children with CF, but is not the sole marker that should be examined in evaluating nutrition.

PMID: 33476226 [PubMed - as supplied by publisher]

Sex Differences in Severe Asthma: Results From Severe Asthma Network in Italy-SANI.

Allergy Asthma Immunol Res. 2021 Mar;13(2):219-228

Authors: Senna G, Latorre M, Bugiani M, Caminati M, Heffler E, Morrone D, Paoletti G, Parronchi P, Puggioni F, Blasi F, Canonica GW, Paggiaro P, SANI Network

Abstract
PURPOSE: After adolescence, asthma is more frequent in females than in males due to different hormonal, immunologic, and occupational/environmental factors. The higher prevalence and severity of the disease in females have already been reported in international registries. The aim of this study was to explore the difference in terms of clinical, functional, and biological characteristics between male and female patients with severe asthma in a real-life, registry-based setting.
METHODS: Baseline data from the Severe Asthma Network in Italy registry were analyzed in 1,123 patients with severe asthma, according to sex.
RESULTS: Almost 2/3 of severe asthmatics were female. Late-onset asthma, obesity and gastro-esophageal reflux were more frequent in females than in males, while previous smoking habits and nasal polyposis were more frequent in males. Females had poor asthma control and a higher number of severe exacerbations leading to hospitalization, in comparison to males. Biomarkers of type 2 inflammation (blood eosinophil, exhaled nitric oxide, and serum immunoglobulin E levels) were significantly higher in males than in females. The type 2 profile (defined by a combination of these 3 biomarkers) was significantly more frequent in males than in females. In multivariate analysis, late-onset asthma and a normal body mass index were only independent variables associated with the type 2 profile, while male sex and age showed only a trend toward the association with the type 2 profile.
CONCLUSIONS: Significant differences may be observed between male and female patients with severe asthma, influencing the asthma pheno-endotyping in both sexes.

PMID: 33474857 [PubMed]

The effect of an intensive residential rehabilitation program on body composition in patients with cystic fibrosis.

Eur J Pediatr. 2021 Jan 20;:

Authors: Van Biervliet S, Declercq D, Dereeper S, Vermeulen D, Würth B, De Guschtenaere A

Abstract
The pulmonary function of patients with cystic fibrosis (CF) is associated with nutritional status not only expressed as body mass index (BMI) but also as fat-free mass index (FFMI). This study evaluated the effect of a residential rehabilitation program on nutritional status (BMI, FFMI). The rehabilitation program provided supervised respiratory and nutritional treatment and daily physical activity for 3 weeks (median stay 20 (19-25) days). At the start and the end of the program, weight, height, pulmonary function, and body composition using dual-energy X-ray absorptiometry were prospectively collected. Supervised weighed food records were obtained, and physical activity intensity was measured using a SenseWear Pro3 Armband. CF-related complications were collected from the patient. Thirty-four patients (21 males, median age 18 years old (12-27)) were included. The diet contained a median of 30 EN% fat, 16 EN% protein, and 52 EN% of carbohydrates. A significant median weight gain (+1.45 kg (0.58; 2.6) (p < 0.0001) and a significant increase in BMI (+0.24 kg/m2 (0.11; 0.38)) (p < 0.0001), FFMI (+0.26 kg/m2 (0.01; 0.55)) (p < 0.0001), and FMI (+0.19 kg/m2 (0.04; 0.41)) (p < 0.0001) were obtained.Conclusion: A short rehabilitation program in individuals with CF between 6 and 40 years old is able to improve nutritional status and body composition.Trial registration: NCT04527796 What is Known: • Fat-free mass depletion is frequently present in CF. • In CF pulmonary function is associated with nutritional status measured as body mass index but also fat-free mass index. What is New: • Nutritional status and body composition improve significantly after a short-term rehabilitation program. • The rehabilitation program was able to improve nutritional outcome even with a diet containing less fat than currently advised in the guidelines.

PMID: 33474579 [PubMed - as supplied by publisher]

Pediatric Resident Education in Pulmonary (PREP): A Subspecialty Preparatory Boot Camp Curriculum for Pediatric Residents.

MedEdPORTAL. 2021 Jan 07;17:11066

Authors: Khan EK, Liptzin DR, Baker J, Meier M, Baker CD, Lockspeiser TM

Abstract
Introduction: Medical errors can occur any time resident physicians transition between rotations, especially to unfamiliar areas such as subspecialty pediatrics. To combat this, we created and implemented the pediatric resident education in pulmonary (PREP) boot camp using Kern's six-step approach to curriculum development.
Methods: PREP was a 5-hour session with multiple high-yield components held on the first day of each new rotation, aimed to prepare residents to care for complex pulmonary inpatients, including those with tracheostomy and ventilator dependence, asthma, and cystic fibrosis. The curriculum was evaluated at multiple time points through surveys of residents and faculty and two formal resident focus group sessions.
Results: PREP was successfully implemented in July 2018 with continued monthly sessions held. Thirty-five residents participated in the first year. Resident perceived preparedness and confidence in taking call duties increased significantly following PREP. All residents rated PREP as extremely helpful or very helpful, the highest ratings possible. Overall, residents preferred active learning strategies. All qualitative data revealed positive effects of PREP. Clinical faculty in the pulmonology division found PREP similarly helpful and felt that PREP better prepared residents to provide care to pulmonary inpatients than our previous model.
Discussion: Our monthly preparatory boot camp on the first day of residents' inpatient pulmonary rotation has improved resident experience, preparedness, and ability to care for complex pulmonary patients. The curriculum was adjusted in response to feedback to increase hands-on time and interactive sessions. Protected time for residents and active learning strategies were key to success of PREP.

PMID: 33473377 [PubMed - in process]

Phenotypic and Genotypic Adaptations in Pseudomonas aeruginosa Biofilms following Long-Term Exposure to an Alginate Oligomer Therapy.

mSphere. 2021 Jan 20;6(1):

Authors: Oakley JL, Weiser R, Powell LC, Forton J, Mahenthiralingam E, Rye PD, Hill KE, Thomas DW, Pritchard MF

Abstract
Chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) evolve to generate environmentally adapted biofilm communities, leading to increased patient morbidity and mortality. OligoG CF-5/20, a low-molecular-weight inhaled alginate oligomer therapy, is currently in phase IIb/III clinical trials in CF patients. Experimental evolution of P. aeruginosa in response to OligoG CF-5/20 was assessed using a bead biofilm model allowing continuous passage (45 days; ∼245 generations). Mutants isolated after OligoG CF-5/20 treatment typically had a reduced biofilm-forming ability and altered motility profile. Genotypically, OligoG CF-5/20 provided no selective pressure on genomic mutations within morphotypes. Chronic exposure to azithromycin, a commonly prescribed antibiotic in CF patients, with or without OligoG CF-5/20 in the biofilm evolution model also had no effect on rates of resistance acquisition. Interestingly, however, cross-resistance to other antibiotics (e.g., aztreonam) was reduced in the presence of OligoG CF-5/20. Collectively, these findings show no apparent adverse effects from long-term exposure to OligoG CF-5/20, instead resulting in both fewer colonies with multidrug resistance (MDR)-associated phenotypes and improved antibiotic susceptibility of P. aeruginosa IMPORTANCE The emergence of multidrug-resistant (MDR) pathogens within biofilms in the cystic fibrosis lung results in increased morbidity. An inhalation therapy derived from alginate, OligoG CF-5/20, is currently in clinical trials for cystic fibrosis patients. OligoG CF-5/20 has been shown to alter sputum viscoelasticity, disrupt mucin polymer networks, and disrupt MDR pseudomonal biofilms. Long-term exposure to inhaled therapeutics may induce selective evolutionary pressures on bacteria within the lung biofilm. Here, a bead biofilm model with repeated exposure of P. aeruginosa to OligoG CF-5/20 (alone and in combination with azithromycin) was conducted to study these long-term effects and characterize the phenotypic and genotypic adaptations which result. These findings, over 6 weeks, show that long-term use of OligoG CF-5/20 does not lead to extensive mutational changes and may potentially decrease the pathogenicity of the bacterial biofilm and improve the susceptibility of P. aeruginosa to other classes of antibiotics.

PMID: 33472983 [PubMed - in process]

Novel Lytic Phages Protect Cells and Mice against Pseudomonas aeruginosa Infection.

J Virol. 2021 Jan 20;:

Authors: Chen F, Cheng X, Li J, Yuan X, Huang X, Lian M, Li W, Huang T, Xie Y, Liu J, Gao P, Wei X, Wang Z, Wu M

Abstract
With the fast emergence of serious antibiotic resistance and the lagged discovery of novel antibacterial drugs, phage therapy for pathogenic bacterial infections has acquired great attention in the clinics. However, development of therapeutic phages also faces tough challenges, such as laborious screening and time to generate effective phage drugs since each phage may only lyse a narrow scope of bacterial strains. Identifying highly effective phages with broad host ranges is crucial for improving phage therapy. Here, we isolated and characterized several lytic phages from various environments specific for Pseudomonas aeruginosa by testing their growth, invasion, host ranges, and potential for killing targeted bacteria. Importantly, we identified several therapeutic phages (HX1, PPY9, and TH15) with broad host ranges to lyse laboratory strains and clinical isolates of P. aeruginosa with multi-drug resistance (MDR) both in vitro and in mouse models. In addition, we analyzed critical genetic traits related to the high-level broad host coverages by genome sequencing and subsequent computational analysis against known phages. Collectively, our findings establish that these novel phages may have potential for further development as therapeutic options for patients who fail to respond to conventional treatments.IMPORTANCE Novel lytic phages isolated from various environmental settings were systematically characterized for their critical genetic traits, morphology structures, host ranges against laboratory strains and clinical multi-drug resistant (MDR) Pseudomonas aeruginosa, and antibacterial capacity both in vitro and in mouse models. First, we characterized the genetic traits and compared with other existing phages. Furthermore, we utilized acute pneumonia induced by laboratorial strain PAO1, and W19, an MDR clinical isolate and chronic pneumonia by agar beads laden with FDR1, a mucoid phenotype strain isolated from the sputum of a cystic fibrosis (CF) patient. Consequently, we found that these phages not only suppress bacteria in vitro but also significantly reduce the infection symptom and disease progression in vivo, including lowered bug burdens, inflammatory responses and lung injury in mice, suggesting that they may be further developed as therapeutic agents against MDR P. aeruginosa.

PMID: 33472935 [PubMed - as supplied by publisher]

Transmission and antibiotic resistance of Achromobacter in cystic fibrosis.

J Clin Microbiol. 2021 Jan 20;:

Authors: Gabrielaite M, Bartell JA, Nørskov-Lauritsen N, Pressler T, Nielsen FC, Johansen HK, Marvig RL

Abstract
Achromobacter species are increasingly being detected in patients with cystic fibrosis (CF), and this emerging pathogen is associated with antibiotic resistance and more severe disease outcomes. Nonetheless, little is known about the extent of transmission and antibiotic resistance development in Achromobacter infections.We sequenced the genomes of 101 clinical isolates of Achromobacter (A. xylosoxidans based on MALDI-TOF/API N20 typing) collected from 51 patients with CF-the largest longitudinal dataset to-date. We performed phylogenetic analysis on the genomes and combined this with epidemiological and antibiotic resistance data to identify patient-to-patient transmission and development of antibiotic resistance.We confirmed that MALDI-TOF/API N20 was not sufficient for Achromobacter species-level typing, and that the population of Achromobacter isolates was composed of five different species where A. xylosoxidans accounted for 52% of infections. Most patients were infected by unique Achromobacter clone types; nonetheless, suspected patient-to-patient transmission cases identified by shared clone types were observed in 35% (N=18) of patients. In 15 of 16 cases the suspected transmissions were further supported by genome- or clinic visit-based epidemiological analysis. Finally, we found that resistance developed over time.We show that whole-genome sequencing (WGS) is essential for Achromobacter species typing and patient-to-patient transmission identification which was identified in A. ruhlandii, A. xylosoxidans and, for the first time, A. insuavis. Furthermore, we show that the development of antibiotic resistance is associated with chronic Achromobacter infections. Our findings emphasize that transmission and antibiotic resistance should be considered in future treatment strategies.

PMID: 33472899 [PubMed - as supplied by publisher]

In silico drug repositioning on F508del-CFTR: A proof-of-concept study on the AIFA library.

Eur J Med Chem. 2021 Jan 13;213:113186

Authors: Orro A, Uggeri M, Rusnati M, Urbinati C, Pedemonte N, Pesce E, Moscatelli M, Padoan R, Cichero E, Fossa P, D'Ursi P

Abstract
Computational drug repositioning is of growing interest to academia and industry, for its ability to rapidly screen a huge number of candidates in silico (exploiting comprehensive drug datasets) together with reduced development cost and time. The potential of drug repositioning has not been fully evaluated yet for cystic fibrosis (CF), a disease mainly caused by deletion of Phe 508 (F508del) of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. F508del-CFTR is thus withheld in the endoplasmic reticulum and rapidly degraded by the ubiquitin/proteasome system. CF is still a fatal disease. Nowadays, it is treatable by some CFTR-rescuing drugs, but new-generation drugs with stronger therapeutic benefits and fewer side effects are still awaited. In this manuscript we report about the results of a pilot computational drug repositioning screening in search of F508del-CFTR-targeted drugs performed on AIFA library by means of a dedicated computational pipeline and surface plasmon resonance binding assay to experimentally validate the computational findings.

PMID: 33472120 [PubMed - as supplied by publisher]

Gene Therapy for Cystic Fibrosis: Lessons Learned and Paths Forward.

Mol Ther. 2021 Jan 12;:

Authors: Choi SH, Engelhardt JF

PMID: 33472034 [PubMed - as supplied by publisher]

CF Monocyte Derived Macrophages Have an Attenuated Response to Extracellular Vesicles Secreted by Airway Epithelial Cells.

Am J Physiol Lung Cell Mol Physiol. 2021 Jan 20;:

Authors: Koeppen K, Nymon AB, Barnaby R, Li Z, Hampton TH, Ashare A, Stanton BA

Abstract
Mutations in CFTR alter macrophage responses, for example, by reducing their ability to phagocytose and kill bacteria. Altered macrophage responses may facilitate bacterial infection and inflammation in the lungs, contributing to morbidity and mortality in cystic fibrosis (CF). Extracellular vesicles (EVs) are secreted by multiple cell types in the lungs and participate in the host immune response to bacterial infection, but the effect of EVs secreted by CF airway epithelial cells (AEC) on CF macrophages is unknown. This report examines the effect of EVs secreted by primary AEC on monocyte derived macrophages (MDM) and contrasts responses of CF and WT MDM. We found that EVs generally increase pro-inflammatory cytokine secretion and expression of innate immune genes in MDM, especially when EVs are derived from AEC exposed to Pseudomonas aeruginosa, and that this effect is attenuated in CF MDM. Specifically, EVs secreted by P. aeruginosa exposed AEC induced immune response genes and increased secretion of pro-inflammatory cytokines, chemoattractants and chemokines involved in tissue repair by WT MDM, but these effects were less robust in CF MDM. We attribute attenuated responses by CF MDM to differences between CF and WT macrophages because EVs secreted by CF AEC or WT AEC elicited similar responses in CF MDM. Our findings demonstrate the importance of AEC EVs in macrophage responses and show that the Phe508del mutation in CFTR attenuates the innate immune response of MDM to EVs.

PMID: 33471607 [PubMed - as supplied by publisher]

Cystic Fibrosis Patients of Minority Race and Ethnicity Less Likely Eligible for CFTR Modulators Based on CFTR Genotype.

Pediatr Pulmonol. 2021 Jan 20;:

Authors: McGarry ME, McColley SA

Abstract
BACKGROUND: CFTR modulators are disease-modifying medications for cystic fibrosis (CF) and are shown to be efficacious for only specific CFTR mutations. CFTR mutation frequency varies by ancestry, which is different from but related to demographic racial and ethnic group. Eligibility for CFTR modulator therapy has not been previously reported by race and ethnicity.
METHODS: We conducted a cross-sectional study of patients in the 2018 CF Foundation Patient Registry. We analyzed the percentage of patients in each US Census defined racial and ethnic group eligible for CFTR modulators based on CFTR mutations approved by the US FDA and then based on both mutations and FDA-approval by age. We compared lung function based on CFTR modulator eligibility and prescription.
FINDINGS: Based on CFTR mutations alone, 92·4% of non-Hispanic white patients, 69.7% of Black/African American patients, 75.6% of Hispanic patients, and 80.5% of other race patients eligible for CFTR modulators. For each CFTR modulator, Black/African American patients were least likely to have eligible mutations, and non-Hispanic white patients were most likely. There was no difference in the disparity between racial and/or ethnic groups with the addition of current FDA-approval by age. The lowest pulmonary function in the cohort was seen in non-Hispanic white, Black/African-American, and Hispanic patients not eligible for CFTR modulators.
INTERPRETATION: Patients with CF from minority groups are less likely to be eligible for CFTR modulators. Because people with CF who are racial and ethnic minorities have increased disease severity and earlier mortality, this will further contribute to health disparities. This article is protected by copyright. All rights reserved.

PMID: 33470563 [PubMed - as supplied by publisher]

Understanding the expanding role of pharmacy services in outpatient cystic fibrosis care.

Pediatr Pulmonol. 2021 Jan 20;:

Authors: Zobell JT, Moss J, Heuser S, Roe L, Young DC

Abstract
Cystic fibrosis (CF) patients utilize an average of 10 (±5) medications per day. Given the complexity of the medication regimen, the CF Foundation (CFF) recommends pharmacists as members of the CF care team. The areas of pharmacy services have been identified in the literature. "Limited access pharmacists" are consulted to answer questions, assist in evaluating serum drug concentrations, provide medication education, and monitoring for drug-drug interactions. Reduction in hospital length of stay has been shown through this collaboration. "Full access pharmacists" provide comprehensive medication therapy management resulting in medication adherence and access improvements, sustainability of treatments, improved provider communication, reduced medication errors and costs, expedited medication refill authorization, increased utilization of respiratory therapists, enhanced discussion of medications with CF team members, and reduction in the number of pharmacies utilized by patients to fill CF medications. An integrated CF pharmacy team are essential members of the multidisciplinary CF care team that have been shown to improvement in CF medication access, increases in body weight and body mass index, reduction in prior authorization submission times, reduction in medication delivery times, expedited medication refill authorizations, increased collaboration with respiratory therapists, augmented discussion of medication with CF team members, and reduction in the number of pharmacies utilized by CF patients. There is a need to further evaluate the impact of outpatient CF pharmacy services due to the improvements in the care on patients and families affected by CF, and as the number of CFF-accredited care centers integrate CF pharmacy teams throughout the country increases. This article is protected by copyright. All rights reserved.

PMID: 33470556 [PubMed - as supplied by publisher]

Does Bordetella pertussis vaccine offer any cross-protection against Bordetella bronchiseptica? Implications for pet owners with cystic fibrosis.

J Clin Pharm Ther. 2021 Jan 20;:

Authors: Moore JE, Rendall JC, Millar BC

Abstract
WHAT IS KNOWN AND OBJECTIVE: The Gram-negative bacterium, Bordetella bronchiseptica, causes lower airway respiratory disease in people with cystic fibrosis (CF), as well as in companion animals, especially dogs. Presently, there are several acellular vaccines available for B. pertussis but no vaccine available for B. bronchiseptica. However given the shared protein homology between these two closely related species, we wished to explore whether pertussis vaccines may offer some cross-protection against B. bronchiseptica.
COMMENT: Bordetella pertussis and B. bronchiseptica are closely related phylogenetically, as well as sharing protein homology in several pertussis vaccine components, including (i) pertussis toxin (PT), (ii) filamentous haemagglutinin (FHA), (iii) pertactin and (iv) fimbriae (types 2 and 3). Given that pertussis vaccine contains cross-reactive antigens with B. bronchiseptica, licensed pertussis vaccines may therefore offer cross-protection against B. bronchiseptica.
WHAT IS NEW AND CONCLUSION: Cystic fibrosis pet owners should ensure that they have an up-to-date vaccination record relating to their pertussis vaccine. Although no monovalent human pertussis vaccines are currently available, licensed non-live booster vaccines for B. pertussis are available for individuals in the age range >10 years old. People with CF should ensure that they are adequately and currently protected against pertussis, to avoid whooping cough, which may also offer some cross-protection against B. bronchiseptica and therefore help further mitigate the risk of zoonotic infection of this organism from pets to their owners.

PMID: 33470435 [PubMed - as supplied by publisher]

Meta-analysis of Efficacy and Safety of Inhaled Ciprofloxacin in Non-cystic Fibrosis Bronchiectasis Patients.

Intern Med J. 2021 Jan 19;:

Authors: Wang S, Zhang A, Yao X

Abstract
BACKGROUND: No antibiotic therapies have been approved for reducing exacerbations and preventing disease progression in non-cystic fibrosis bronchiectasis (NCFB) patients. Several recent clinical studies have investigated the feasibility of inhaled ciprofloxacin in NCFB, whereas the results were controversial.
METHOD: Electrical databases Medline and Cochrane library were retrieved from inception through December, 2019. Randomized controlled trials (RCTs) comparing inhaled ciprofloxacin and placebo were selected. The primary outcomes were time to first exacerbation, frequency of exacerbations and the change in sputum Pseudomonas aeruginosa density.
RESULTS: A total of five articles involving 6 RCTs were finally included in the analysis. The time to first exacerbation was significantly prolonged by inhaled ciprofloxacin (Hazard ratio: 0.72, 95% confidence interval (CI): 0.63-0.82), with low heterogeneity (I2 = 23%). Inhalation of ciprofloxacin significantly reduced frequency of exacerbations (Risk ratio: 0.70, 95% CI: 0.61-0.79) and decreased density of sputum Pseudomonas aeruginosa (Weighted mean difference: -2.11 log10 CFU/g, 95% CI: -2.96 to -1.27 log10 CFU/g) compared with placebo. No significant between-group differences in mortality, adverse events and discontinuation rate were observed. Further indirect treatment comparison showed no differences between the two types of inhaled ciprofloxacin in all outcomes of interest.
CONCLUSION: Ciprofloxacin inhalation treatment significantly prolonged the time to first exacerbation, reduced the frequency of exacerbations and decreased sputum Pseudomonas aeruginosa density, and was well-tolerated. Ciprofloxacin inhalation is promising in treatment of NCFB. This article is protected by copyright. All rights reserved.

PMID: 33469994 [PubMed - as supplied by publisher]