J Cyst Fibros. 2023 Mar 23:S1569-1993(23)00075-9. doi: 10.1016/j.jcf.2023.03.011. Online ahead of print.

ABSTRACT

BACKGROUND: Overweight and obesity among people with cystic fibrosis (pwCF) has become more prevalent since the widespread adoption of CF transmembrane conductance regulator (CFTR) modulator therapies and presents a new challenge for nutritional care. We aimed to explore how clinicians working in CF care approach the management of adults with overweight and obesity.

METHODS: We conducted semi-structured interviews with n = 20 clinicians (n = 6 physiotherapists, n = 6 doctors and n = 8 dietitians) working in 15 adult CF centres in the United Kingdom. The interviews explored their perspectives and current practices caring for people with CF and overweight/obesity. Data were analysed using reflexive thematic analysis.

RESULTS: Four main themes were identified: 1) challenges of raising the topic of overweight and obesity in the CF clinic (e.g., clinician-patient rapport and concerns around weight stigma); 2) the changing landscape of assessment due to CF-specific causes of weight gain: (e.g., impact of CFTR modulators and CF legacy diet) 3) presence of clinical equipoise for weight management due to the lack of CF-specific evidence on the consequences of obesity and intentional weight loss (e.g., unclear consequences on respiratory outcomes and risk of weight related co-morbidities) and 4) opportunities for a safe, effective, and acceptable weight management treatment for people with CF (e.g., working collaboratively with current multidisciplinary CF care).

CONCLUSIONS: Approaching weight management in the CF setting is complex. Trials are needed to assess the equipoise of weight management interventions in this group and CF-specific issues should be considered when developing such interventions.

PMID:36966039 | DOI:10.1016/j.jcf.2023.03.011

J Cyst Fibros. 2023 Mar 23:S1569-1993(23)00077-2. doi: 10.1016/j.jcf.2023.03.013. Online ahead of print.

NO ABSTRACT

PMID:36966038 | DOI:10.1016/j.jcf.2023.03.013

J Cyst Fibros. 2023 Mar 23:S1569-1993(23)00071-1. doi: 10.1016/j.jcf.2023.03.007. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) clinicians may see patients who have difficult-to-manage symptoms that do not have a clear CF-related etiology, such as unusual gastrointestinal (GI) complaints, vasculitis, or arthritis. Alterations in immunity, inflammation and intraluminal dysbiosis create a milieu that may lead to autoimmunity, and the CF transmembrane regulator protein may have a direct role as well. While autoantibodies and other autoimmune markers may develop, these may or may not lead to organ involvement, therefore they are helpful but not sufficient to establish an autoimmune diagnosis. Autoimmune involvement of the GI tract is the best-established association. Next steps to understand autoimmunity in CF should include a more in-depth assessment of the community perspective on its impact. In addition, bringing together specialists in various fields including, but not limited to, pulmonology, gastroenterology, immunology, and rheumatology, would lead to cross-dissemination and help define the path forward in basic science and clinical practice.

PMID:36966037 | DOI:10.1016/j.jcf.2023.03.007

iScience. 2023 Mar 24;26(4):106475. doi: 10.1016/j.isci.2023.106475. eCollection 2023 Apr 21.

ABSTRACT

Chronic airway infections with Pseudomonas aeruginosa are the major co-morbidity in most people with cystic fibrosis (CF) sustained by neutrophils as the major drivers of lung inflammation, damage, and remodeling. Phagocytosis assays were performed with clonal consortia of longitudinal P. aeruginosa airway isolates collected from people with CF since the onset of lung colonization until patient's death or replacement by another clone. The extra- and intracellular abundance of individual strains was assessed by deep amplicon sequencing of strain-specific single nucleotide variants in the bacterial genome. The varied microevolution of the accessory genome of the P. aeruginosa clones during mild and severe courses of infection corresponded with a differential persistence of clonal progeny in the neutrophil phagosome. By simultaneously exposing the ancestor and its progeny to the same habitat, the study recapitulated the time lapse of the temporal change of the fitness of the clone to survive in neutrophils.

PMID:37096049 | PMC:PMC10122015 | DOI:10.1016/j.isci.2023.106475

J Cardiothorac Vasc Anesth. 2023 Feb 23:S1053-0770(23)00114-3. doi: 10.1053/j.jvca.2023.02.029. Online ahead of print.

ABSTRACT

OBJECTIVE: Life expectancy for lung-transplant patients, especially those with cystic fibrosis (CF), is leading increasingly to more retransplantations.

DESIGN: Retrospective monocentric cohort study.

SETTING: Foch University Hospital, Suresnes, France.

PARTICIPANTS: CF patients having had a primary double-lung transplantation (pLgTx) or a retransplantation (reLgTx) from 2012 to 2021.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The authors compared the main intraoperative and early postoperative features between pLgTx (n = 258) and reLgTx (n = 24). Demographic characteristics were similar. No patients with retransplantations had a preoperative bridge with extracorporeal membrane oxygenation (ECMO); however, 23 patients had it in the pLgTx group (p = 0.24). Patients with retransplants had longer second graft ischemic time (p = 0.02), larger intraoperative bleeding volume (p = 0.001) and blood transfusion (p = 0.009 for packed red blood cells), increased blood lactate concentrations (p = 0.002), and higher norepinephrine dose at end-surgery (p = 0.001). Extracorporeal membrane oxygenation was used during surgery in 94 patients in the pLgTx group and 12 patients in the reLgTx group (p = 0.39). Extracorporeal membrane oxygenation could not be weaned after surgery in 55 patients in the pLgTx group and 4 in the reLgTx group (p = 0.54). Despite worse preoperative renal function in the reLgTx group (p < 0.001), there was no difference concerning renal replacement therapy in the intensive care unit between groups (p = 0.08). There were no differences between groups concerning the main complications, including primary graft dysfunction. Although the difference was not statistically different (p = 0.17), mortality was 3 times higher in the reLgTx group.

CONCLUSIONS: Intraoperative period of retransplantation was more convoluted but had a similar ECMO profile to primary transplantation. In addition, the early postoperative period was similar.

PMID:36964081 | DOI:10.1053/j.jvca.2023.02.029

J Cyst Fibros. 2023 Mar 22:S1569-1993(23)00066-8. doi: 10.1016/j.jcf.2023.03.002. Online ahead of print.

ABSTRACT

BACKGROUND: Phase 3 clinical trials showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in people with cystic fibrosis (CF) with ≥1 F508del-CFTR allele. To assess long-term effects of ELX/TEZ/IVA under real-world conditions of use, a 5-year observational registry-based study is being conducted. We report interim results from the first 2 years of follow-up.

METHODS: The study included people with CF in the US Cystic Fibrosis Foundation Patient Registry (CFFPR) who initiated ELX/TEZ/IVA between October 2019 and December 2020. Pulmonary exacerbations (PEx), percent predicted forced expiratory volume in 1 second (ppFEV1), hospitalizations, bacterial pathogens, body mass index (BMI), CF complications and comorbidities, and liver function tests (LFTs) after treatment initiation were compared with the 5-year pre-treatment period. Death and lung transplantation were assessed relative to 2019 CFFPR data.

RESULTS: 16,116 people with CF were included (mean treatment duration 20.4 months). Among those with 5 years of pre-treatment data, mean PEx/patient/year declined to 0.18 (95% CI: 0.17, 0.19) in Years 1 and 2 post-treatment from 0.86 (95% CI: 0.83, 0.88) in the baseline year (79% reduction), after a continued increase observed pre-treatment. Similarly, a decline in mean hospitalizations/patient/year was observed in Year 1 that was sustained in Year 2 (74% reduction from baseline year). The mean absolute change in ppFEV1 from baseline was +8.2 percentage points (95% CI: 8.0, 8.4) in Year 1 and +8.9 percentage points (95% CI: 8.7, 9.1) in Year 2, after a continued decline observed pre-treatment. Positive bacterial cultures decreased for all evaluated pathogens, and mean BMI increased by 1.6 kg/m2 (95% CI: 1.5, 1.6) by Year 2. No new safety concerns were identified based on evaluation of CF complications, comorbidities, and LFTs. The annualized rates of death (0.47% [95% CI: 0.39, 0.55]) and lung transplantation (0.16% [95% CI: 0.12, 0.22]) were considerably lower than reported in 2019 (1.65% and 1.08%, respectively).

CONCLUSIONS: ELX/TEZ/IVA treatment was associated with sustained improvements in lung function, reduced frequency of PEx and all-cause hospitalization, increased BMI, and lower prevalence of positive bacterial cultures. Additionally, there was a 72% lower rate of death and 85% lower rate of lung transplantation relative to the year before ELX/TEZ/IVA availability. These results, from the largest cohort of ELX/TEZ/IVA-treated people to date, extend our understanding of the broad clinical benefits of ELX/TEZ/IVA.

PMID:36963986 | DOI:10.1016/j.jcf.2023.03.002

Clin Nutr ESPEN. 2023 Apr;54:349-373. doi: 10.1016/j.clnesp.2023.02.006. Epub 2023 Feb 10.

ABSTRACT

BACKGROUND: Increasing evidence suggests that vitamin D is associated with pulmonary health, which may benefit children and young people diagnosed with Cystic Fibrosis (cypCF). Therefore, the aim of this systematic review was to evaluate primary research to establish associations between 25OHD and pulmonary health in cypCF.

METHODS: Electronic databases were searched with keywords related to CF, vitamin D, children/young people and pulmonary function. Included studies were cypCF (aged ≤21 years) treated in a paediatric setting. The primary outcome was lung function [forced expiratory volume in 1 s (FEV1% predicted)] and secondary outcomes were rate of pulmonary exacerbations, 25OHD status and growth. Evidence was appraised for risk of bias using the CASP tool, and quality using the EPHPP tool. A Meta-analysis was performed.

RESULTS: Twenty-one studies were included with mixed quality ratings and heterogeneity of reported outcomes. The Meta-analysis including 5 studies showed a significantly higher FEV1% predicted in the 25OHD sufficiency compared to the deficiency group [FEV1% predicted mean difference (95% CI) was 7.71 (1.69-13.74) %; p = 0.01]. The mean ± SD FEV1% predicted for the sufficient (≥75 nmol/L) vs. deficient (<50 nmol/L) group was 94.7 ± 31.9% vs. 86.9 ± 13.2%; I2 = 0%; χ2 = 0.5; df = 4). Five studies (5/21) found significantly higher rate of pulmonary exacerbations in those who were 25OHD deficient when compared to the sufficient group and negative associations between 25OHD and FEV% predicted. The effects of vitamin D supplementation dosages on 25OHD status (10/21) varied across studies and no study (12/21) showed associations between 25OHD concentration and growth.

CONCLUSION: This systematic review suggests that 25OHD concentration is positively associated with lung function and a concentration of >75 nmol/L is associated with reduced frequency of pulmonary exacerbations, which may slow lung function decline in cypCF. Future randomised clinical trials and mechanistic studies are warranted.

PMID:36963882 | DOI:10.1016/j.clnesp.2023.02.006

Pathog Dis. 2023 Mar 24:ftad003. doi: 10.1093/femspd/ftad003. Online ahead of print.

ABSTRACT

Burkholderia contaminans, a species of the Burkholderia cepacia complex-prevalent in certain Latin-American and European countries-can cause chronic pulmonary infection in persons with cystic fibrosis. Our aim was to gain insights into long-term lung infections with a focus on correlating how bacterial phenotypic traits in the chronic infection impact on patients´ clinical outcome. Genotypic characteristics of 85 B. contaminans isolates recovered from 70 patients were investigated. For 16 of those patients, the clinical status and bacterial phenotypic characteristics, e. g., several virulence factors, phenotypic variants, and the antimicrobial susceptibility pattern, were evaluated. Two clones were found in the whole bacterial population: i) the multiresistant ST 872 PCR-recA-RFLP-HaeIII-K-pattern clone which carries a pathogenic island homologous to BcenGI11 of B. cenocepacia J2315, and ii) the ST 102 PCR-recA-RFLP-HaeIII-AT-pattern clone. The emergence of certain bacterial phenotypes in the chronic infection such as the nonmucoid phenotype, small colony variants, brownish pigmented colonies, and hypermutators, proved to be, together with co-infection with Pseudomonas aeruginosa, the possible markers of more challenging infections and poor prognosis. The presence of co-colonizers and the bacterial phenotypes that are especially adapted to persist in long-term respiratory tract infections have a crucial role in patients' clinical outcomes.

PMID:36963774 | DOI:10.1093/femspd/ftad003

Am J Respir Crit Care Med. 2023 Mar 24. doi: 10.1164/rccm.202303-0468ED. Online ahead of print.

NO ABSTRACT

PMID:36961916 | DOI:10.1164/rccm.202303-0468ED

Dalton Trans. 2023 Mar 24. doi: 10.1039/d3dt00287j. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is an opportunistic, Gram-negative bacterium, involved in severe infections associated with cystic fibrosis, pneumonia, burn wounds, ocular diseases, and immunosuppressive illnesses, and is a major cause of intrahospital infections. This bacterium is also one of the most commercially and biotechnologically significant microorganisms, since it can produce valuable biomolecules which represent a rich source of potential drug candidates. On the other hand, metal complexes have been used in medicine for both therapeutic and diagnostic purposes since ancient times. This class of compounds can adopt different geometries and generally have a three-dimensional shape, contributing to their higher clinical success compared to flat purely organic compounds. In the present review article, attention has been devoted to the three natural products derived from P. aeruginosa, namely pyocyanin, pyochelin, and pyoverdine(s) and their ability to form complexes with different metal ions, including iron(II/III), manganese(II/III), gallium(III), chromium(III), nickel(II), copper(II), zinc(II) and cadmium(II). Investigation of the coordination properties of pyocyanin, pyochelin, and pyoverdine(s) towards these metal ions is important because the resulting bacterially derived natural product-metal complex can serve as a model for the study of metal ion metabolism (transport and storage) in living systems and might also be considered as a novel therapeutic agent for potential use in medicine.

PMID:36961520 | DOI:10.1039/d3dt00287j

Front Microbiol. 2023 Mar 7;14:1099623. doi: 10.3389/fmicb.2023.1099623. eCollection 2023.

ABSTRACT

Burkholderia contaminans, an emerging pathogen related to cystic fibrosis, is known to cause potentially fatal infections in humans and ruminants, especially in immunocompromised individuals. However, the immune responses in cows following its infection have not been fully elucidated. In this study, T- and B-lymphocytes-mediated immune responses were evaluated in 15 B. contaminans-induced mastitis cows and 15 healthy cows with multi-parameter flow cytometry. The results showed that infection with B. contaminans was associated with a significant decrease in the number and percentage of B lymphocytes but with a significant increase in the proportion of IgG+CD27+ B lymphocytes. This indicated that humoral immune response may not be adequate to fight intracellular infection, which could contribute to the persistent bacterial infection. In addition, B. contaminans infection induced significant increase of γδ T cells and double positive (DP) CD4+CD8+ T cells but not CD4+ or CD8+ (single positive) T cells in blood. Phenotypic analysis showed that the percentages of activated WC1+ γδ T cells in peripheral blood were increased in the B. contaminans infected cows. Interestingly, intracellular cytokine staining showed that cattle naturally infected with B. contaminans exhibited multifunctional TNF-α+IFN-γ+IL-2+ B. contaminans-specific DP T cells. Our results, for the first time, revealed a potential role of IgG+CD27+ B cells, CD4+CD8+ T cells and WC1+ γδ T cells in the defense of B. contaminans-induced mastitis in cows.

PMID:36960295 | PMC:PMC10028201 | DOI:10.3389/fmicb.2023.1099623

Eur Respir J. 2023 Mar 23;61(3):2202009. doi: 10.1183/13993003.02009-2022. Print 2023 Mar.

NO ABSTRACT

PMID:36958745 | DOI:10.1183/13993003.02009-2022

Am J Respir Cell Mol Biol. 2023 Mar 23. doi: 10.1165/rcmb.2022-0241OC. Online ahead of print.

ABSTRACT

The cystic fibrosis transmembrane conductance regulator (CFTR) is a tightly regulated anion channel that mediates chloride and bicarbonate conductance in many epithelia and in other tissues, but whether its regulation varies depending on the cell type has not been investigated. Epithelial CFTR expression is highest in rare cells called ionocytes. We studied CFTR regulation in control and ionocyte-enriched cultures by transducing bronchial basal cells with adenoviruses that contain only eGFP or FOXI1 + eGFP as separate polypeptides. FOXI1 dramatically increased the number of transcripts for ionocyte markers ASCL3, BSND, ATP6V1G3, ATP6V0D2, KCNMA1, and CFTR without altering those for secretory (SCGB1A1), basal (KRT5, KRT6, TP63), goblet (MUC5AC) or ciliated (FOXJ1) cells. The number of cells displaying strong FOXI1 expression was increased 7-fold and there was no evidence for a broad increase in background immunofluorescence. Total CFTR mRNA and protein levels increased 10-fold and 2.5-fold, respectively. Ionocyte-enriched cultures displayed elevated basal current, increased adenylyl cyclase 5 expression, and tonic suppression of CFTR activity by the phosphodiesterase PDE1C, which has not been shown previously to regulate CFTR activity. The results indicate that CFTR regulation depends on cell type and identify PDE1C as a potential target for therapeutics that aim to increase CFTR function specifically in ionocytes.

PMID:36952679 | DOI:10.1165/rcmb.2022-0241OC

Am J Respir Crit Care Med. 2023 Mar 23. doi: 10.1164/rccm.202211-2096OC. Online ahead of print.

ABSTRACT

Rationale: Type 2 inflammation has been described in people with cystic fibrosis (CF). Whether loss of cystic fibrosis transmembrane conductance regulator (CFTR) function contributes directly to a type 2 inflammatory response has not been fully defined. Objectives: The potent alarmin IL-33 has emerged as a critical regulator of type 2 inflammation. We tested the hypothesis that CFTR-deficiency increases IL-33 expression/release and deletion of IL-33 reduces allergen-induced inflammation in the CF lung. Methods: Human airway epithelial cells (AECs) grown from non-CF and CF cell lines and Cftr+/+ and Cftr-/- mice, were used in this study. Pulmonary inflammation in Cftr+/+ and Cftr-/- mice with and without IL-33 or ST2 germline deletion was determined by histological analysis, bronchoalveolar lavage (BAL) and cytokine analysis. Measurements and Main Results: Following allergen challenge, CF human AECs and Cftr-/- mice had increased IL-33 expression compared to control AECs and Cftr+/+ mice, respectively. DUOX-1 expression was increased in CF human AECs and Cftr-/- mouse lungs compared to control AECs and lungs from Cftr+/+ mice and was necessary for the increased IL-33 release in Cftr-/- mice compared Cftr+/+ mice. IL-33 stimulation of Cftr-/- CD4+ cells resulted in increased type 2 cytokine production compared to Cftr+/+ CD4+ cells. Deletion of IL-33 or ST2 decreased both type 2 inflammation and neutrophil recruitment in Cftr-/- mice compared to Cftr+/+ mice. Conclusions: Absence of CFTR reprograms airway epithelial IL-33 release and licenses IL-33-dependent inflammation. Modulation of the IL-33/ST2 axis represents a novel therapeutic target in CF type 2 high and neutrophilic inflammation.

PMID:36952660 | DOI:10.1164/rccm.202211-2096OC

Mol Ther Methods Clin Dev. 2023 Mar 2;29:70-80. doi: 10.1016/j.omtm.2023.02.015. eCollection 2023 Jun 8.

ABSTRACT

The efficacy of redosing the recombinant adeno-associated virus (rAAV) vector rAAV2.5T to ferret lung is limited by AAV neutralizing antibody (NAb) responses. While immunosuppression strategies have allowed for systemic rAAV repeat dosing, their utility for rAAV lung-directed gene therapy is largely unexplored. To this end, we evaluated two immunosuppression (IS) strategies to improve repeat dosing of rAAV2.5T to ferret lungs: (1) a combination of three IS drugs (Tri-IS) with broad coverage against cellular and humoral responses (methylprednisolone [MP], azathioprine, and cyclosporine) and (2) MP alone, which is typically used in systemic rAAV applications. Repeat dosing utilized AAV2.5T-SP183-fCFTRΔR (recombinant ferret CFTR transgene), followed 28 days later by AAV2.5T-SP183-gLuc (for quantification of transgene expression). Both the Tri-IS and MP strategies significantly improved transgene expression following repeat dosing and reduced AAV2.5T NAb responses in the bronchioalveolar lavage fluid (BALF) and plasma, while AAV2.5T binding antibody subtypes and cellular immune responses by ELISpot were largely unchanged by IS. One exception was the reduction in plasma AAV2.5T binding immunoglobulin G (IgG) in both IS groups. Only the Tri-IS strategy significantly suppressed splenocyte expression of IFNA (interferon α [IFN-α]) and IL4. Our studies suggest that IS strategies may be useful in clinical application of rAAV targeting lung genetic diseases such as cystic fibrosis.

PMID:36950451 | PMC:PMC10025970 | DOI:10.1016/j.omtm.2023.02.015

Trials. 2023 Mar 22;24(1):211. doi: 10.1186/s13063-023-07076-8.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a rare, inherited, life-limiting condition predominantly affecting the lungs, for which there is no cure. The disease is characterized by recurrent pulmonary exacerbations (PEx), which are thought to drive progressive lung damage. Management of these episodes is complex and generally involves multiple interventions targeting different aspects of disease. The emergence of innovative trials and use of Bayesian statistical methods has created renewed opportunities for studying heterogeneous populations in rare diseases. Here, we present the protocol for the BEAT CF PEx cohort, a prospective, multi-site, perpetual, platform enrolling adults and children with CF. The BEAT CF PEx cohort will be used to evaluate the comparative effectiveness of interventions for the treatment of PEx requiring intensive therapy (PERITs), with a primary focus on short-term improvements in lung function. This will be achieved through the conduct of cohort-nested studies, including adaptive clinical trials, within the BEAT CF PEx cohort. This protocol will outline key features of the BEAT CF PEx cohort, including the design, implementation, data collection and management, governance and analysis, and dissemination of results.

METHODS: This platform will be conducted across multiple sites, commencing with CF treatment centers in Australia. People of all ages with a clinical diagnosis of CF will be eligible to participate, except those who have previously received a lung transplant. Data including demographic and clinical information, treatment details, and outcomes (including safety, microbiology, and patient-reported outcome measures including quality of life scores) will be systematically collected and securely stored via a digital centralized trial management system (CTMS). The primary endpoint is the absolute change in the percentage predicted forced expiratory volume in 1 s (ppFEV1) from the commencement of intensive therapy to 7 to 10 days afterwards.

DISCUSSION: The BEAT CF PEx cohort will report clinical, treatment, and outcome data for PEx among people with CF and is intended to serve as a core (master) protocol for future nested, interventional trials evaluating treatment(s) for these episodes. The protocols for nested sub-studies are beyond the scope of this document and will be reported separately.

TRIAL REGISTRATION: ANZCTR BEAT CF Platform - ACTRN12621000638831. Registration date: Sept. 26, 2022.

PMID:36949472 | DOI:10.1186/s13063-023-07076-8

Nature. 2023 Mar 22. doi: 10.1038/s41586-023-05854-7. Online ahead of print.

ABSTRACT

The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel that regulates salt and fluid homeostasis across epithelial membranes1. Alterations in CFTR cause cystic fibrosis, a fatal disease without a cure2,3. Electrophysiological properties of CFTR have been analysed for decades4-6. The structure of CFTR, determined in two globally distinct conformations, underscores its evolutionary relationship with other ATP-binding cassette transporters. However, direct correlations between the essential functions of CFTR and extant structures are lacking at present. Here we combine ensemble functional measurements, single-molecule fluorescence resonance energy transfer, electrophysiology and kinetic simulations to show that the two nucleotide-binding domains (NBDs) of human CFTR dimerize before channel opening. CFTR exhibits an allosteric gating mechanism in which conformational changes within the NBD-dimerized channel, governed by ATP hydrolysis, regulate chloride conductance. The potentiators ivacaftor and GLPG1837 enhance channel activity by increasing pore opening while NBDs are dimerized. Disease-causing substitutions proximal (G551D) or distal (L927P) to the ATPase site both reduce the efficiency of NBD dimerization. These findings collectively enable the framing of a gating mechanism that informs on the search for more efficacious clinical therapies.

PMID:36949202 | DOI:10.1038/s41586-023-05854-7

AAPS PharmSciTech. 2023 Mar 22;24(4):85. doi: 10.1208/s12249-023-02548-1.

ABSTRACT

A jet nebulizer sprays a fine mist or aerosol directly into the lungs to reduce inflammation, expand airways, and make breathing easier for respiratory patients. Asthma, COPD, emphysema, and cystic fibrosis are treated with jet nebulizers. They are chosen over other nebulizers for their shorter treatment time and wider medication compatibility. For mechanically ventilated patients, jet nebulizers humidify oxygen to provide bronchodilators, antibiotics, and other respiratory medications. Additionally, they treat pneumonia, bronchitis, and other lung infections. Aerosol therapy requires medical jet nebulizers. However, experiment setup is time-consuming and challenging to enhance smaller droplet output. The study is aimed at enhancing the nebulizer and process parameters using numerical simulation and comparing the results to experimental data from the Malvern Spraytec™ laser diffraction system. This numerical model improves nebulization knowledge and predicts process parameters that affect output. Ansys Fluent was used to analyze a Creo-designed jet nebulizer solid model. The Spraytec™ experimental method was utilized to characterize fluticasone propionate's aerosol output and build the best nebulizer. Laser diffraction and computational fluid dynamics (CFD) analysis measured the nebulizer aerosol output. Comparing particle size data between 2 and 5 μm. The results are similar, with a difference of 4.20%. Taguchi optimization found the optimal process parameter, and a conformation test enhanced the process parameter. The nebulizer generates 8.57% more fluticasone propionate at optimal particle size. The optimized nebulizer generates aerosols reliably and speeds up patient recovery.

PMID:36949186 | DOI:10.1208/s12249-023-02548-1

J Cyst Fibros. 2023 Mar 20:S1569-1993(23)00076-0. doi: 10.1016/j.jcf.2023.03.012. Online ahead of print.

NO ABSTRACT

PMID:36948912 | DOI:10.1016/j.jcf.2023.03.012

Patient. 2023 Mar 22. doi: 10.1007/s40271-023-00619-w. Online ahead of print.

ABSTRACT

Patient registries fulfill a number of key roles for clinicians, researchers, non-profit organizations, payers, and policy makers. They can help the field understand the natural history of a condition, determine the effectiveness of interventions, measure safety, and audit the quality of care provided. Successful registries in cystic fibrosis, Duchenne's muscular dystrophy, and other rare diseases have become a model for accelerating progress. However, the complex tasks required to develop a modern registry can seem overwhelming, particularly for those who are not from a technical background. In this Education article, a team of co-authors from across patient advocacy, technology, privacy, and commercial perspectives who have worked on a number of such projects offer a "Registry 101" primer to help get started. We will outline the promise and potential of patient registries with worked case examples, identify some of the key technical considerations you will need to consider, describe the type of data you might want to collect, consider privacy risks to protect your users, sketch out some of the paths towards long-term financial sustainability we have observed, and conclude with plans to mitigate some of the challenges that can occur and signpost interested readers to further resources. While rapid growth in the digital health market has presented numerous opportunities to those at the beginning of their journey, it is important to start with the long-term goals in mind and to benefit from the learnings of those who have walked this path before.

PMID:36947286 | DOI:10.1007/s40271-023-00619-w