J Cyst Fibros. 2023 Nov 11:S1569-1993(23)01673-9. doi: 10.1016/j.jcf.2023.11.002. Online ahead of print.

ABSTRACT

BACKGROUND: The nutritional status of children with cystic fibrosis (CF), as assessed by their body mass index percentile (BMIp), is a critical determinant of long-term health outcomes. While the intestinal microbiome plays an important role in nutrition, little is known regarding the relationship of the microbiome and BMIp in children with CF.

METHODS: Pediatric patients (< 18 years old) with CF and healthy comparison patients (HCs) were enrolled in the study and stool samples obtained. BMIp was categorized as Green Zone (BMIp > 50th), Yellow Zone (BMIp 25th-49th) and Red Zone (BMIp < 25th). Intestinal microbiome assessment was performed via 16S rRNA gene sequencing; microbial richness, diversity, and differential species abundance were assessed.

RESULTS: Stool samples were collected from 107 children with CF and 50 age-matched HCs. Compared to HCs, children with CF were found to have lower bacterial richness, alpha-diversity, and a different microbial composition. When evaluating them by their BMIp color zone, richness and alpha-diversity were lowest in those in the Red Zone. In addition, an unclassified amplicon sequence variant (ASV) of Blautia, a known butyrate-producing anaerobe, was of lowest abundance in children in the Red Zone.

CONCLUSION: Children with CF have a dysbiotic intestinal microbiome with specific changes that accompany changes in BMIp. Longitudinal assessments of the microbiome and its metabolic activities over time are needed to better understand how improvements in the microbiome may improve nutrition and enhance long-term survival in children with CF.

PMID:37953184 | DOI:10.1016/j.jcf.2023.11.002

J Cyst Fibros. 2023 Nov 10:S1569-1993(23)01668-5. doi: 10.1016/j.jcf.2023.10.023. Online ahead of print.

ABSTRACT

BACKGROUND: Males with cystic fibrosis (MwCF) have unique sexual and reproductive health (SRH) concerns. This study investigates multidisciplinary CF clinician perspectives related to SRH for MwCF in the current era of CF care.

METHODS: We surveyed multidisciplinary clinicians exploring attitudes, practices, and preferences toward male CF SRH care. We compared responses across groups by population served (pediatric vs. adult vs. both pediatric and adult MwCF) using chi square/Fisher's exact tests.

RESULTS: A total of 297 clinicians completed the survey (41 % pediatric, 36 % adult, 23 % both; 27 % physicians, 24 % social workers, 11 % nurses, 41 % other). Nearly all (98 %) believed the CF team had a role in SRH care with 75 % believing they should be primarily responsible. Pediatric clinicians were less likely to deem SRH topics important and less likely to report annual discussions compared to adult colleagues (all p<0.05). Pediatric clinicians reported less comfort in their SRH knowledge than adult colleagues (p<0.001) and in their ability to provide SRH care (p<0.05). Common barriers endorsed by respondents included lack of SRH knowledge (75 %) and presence of family/partners in exam room (64 %). A majority rated SRH screening tools (91 %), partnerships with SRH specialists (90 %), clinician training (83 %), and management algorithms (83 %) as potential facilitators.

CONCLUSION: Multidisciplinary CF clinicians perceive SRH for MwCF as important but report suboptimal SRH discussions. Pediatric clinicians report significantly less comfort and skill in discussing and managing male SRH. Identified barriers and facilitators should be used to improve SRH care for MwCF.

PMID:37953183 | DOI:10.1016/j.jcf.2023.10.023

J Cyst Fibros. 2023 Nov 10:S1569-1993(23)01663-6. doi: 10.1016/j.jcf.2023.10.015. Online ahead of print.

ABSTRACT

BACKGROUND: Care guidelines for cystic fibrosis (CF) have been developed to enhance consistent care and to improve health outcomes. We determined if adherence to CF care guidelines predicted P. aeruginosa incidence rates (Pa-IR) at U.S. CF centers in 2018.

METHODS: This cross-sectional CF Foundation Patient Registry study included 82 adult and 132 pediatric centers. Adherence to 12 guidelines was defined categorically (guideline met) or as a continuous measure (proportion of patients being treated/evaluated per guideline). Association of adherence to individual guidelines with Pa-IR, accounted for center and patient characteristics relevant to Pa-IR and were modeled using random forests and weighted-least-squares (WLS) analyses.

RESULTS: The mean Pa-IR was 0.2 cases/patient-years at risk (SE 0.0074) for all centers combined. Guideline adherence was lowest for ≥4 bacterial cultures/year (54% of centers) and annual oral glucose tolerance test (OGTT) (48% of centers), and highest for annual non-tuberculous mycobacteria (NTM) sputum culture (98%). The mean number of guidelines met was 6.7 and higher for pediatric (7.3) than adult (5.6) centers, (p<0.001). The number of guidelines met correlated negatively with Pa-IR (β=-0.007, p = 0.043). Macrolide prescription and annual OGTT per guideline were associated with lower and higher Pa-IR, respectively. Centers with lower center-wide lung function, higher proportion of pwCF with low body-mass index, and location in the Southwest had higher Pa-IR.

CONCLUSION: Overall adherence to guidelines was high except for performing ≥4 bacterial cultures/year and OGTT. Higher Pa-IR was associated with center characteristics and lower guideline adherence. The lower Pa-IR with greater adherence to guidelines suggests that focusing on quality care can positively impact Pa-IR.

PMID:37953182 | DOI:10.1016/j.jcf.2023.10.015

J Cyst Fibros. 2023 Nov 10:S1569-1993(23)01667-3. doi: 10.1016/j.jcf.2023.10.022. Online ahead of print.

ABSTRACT

BACKGROUND: Most males with cystic fibrosis (mwCF) are infertile but with CF transmembrane conductance regulator (CFTR) modulator-conferred benefits, more are utilizing assisted reproductive technologies (ART). Administration of normal human doses of modulators in animal reproductive models caused no genotoxicity; no human data exists. Potential health decline following modulator discontinuation makes the decision to withhold therapy during reproduction challenging.

METHODS: From August-October 2021, international CF clinicians completed an anonymous questionnaire regarding mwCF who used modulators during reproduction.

RESULTS: We received 42 surveys for mwCF with partner pregnancies. Forty of 42 mwCF utilized ART; 35 continued modulators during sperm retrieval and 40/42 during partner pregnancy. One of four males who discontinued modulators experienced clinical deterioration. First trimester miscarriages occurred in 11.9 % of partner pregnancies. No congenital anomalies were reported.

CONCLUSIONS: Use of CFTR modulators during reproduction and partner pregnancy in mwCF did not result in a higher-than-expected miscarriage rate nor congenital anomalies.

PMID:37953181 | DOI:10.1016/j.jcf.2023.10.022

Nat Commun. 2023 Nov 11;14(1):7322. doi: 10.1038/s41467-023-42948-2.

ABSTRACT

Approximately 10% of Cystic Fibrosis (CF) patients, particularly those with CF transmembrane conductance regulator (CFTR) gene nonsense mutations, lack effective treatments. The potential of gene correction therapy through delivery of the CRISPR/Cas system to CF-relevant organs/cells is hindered by the lack of efficient genome editor delivery carriers. Herein, we report improved Lung Selective Organ Targeting Lipid Nanoparticles (SORT LNPs) for efficient delivery of Cas9 mRNA, sgRNA, and donor ssDNA templates, enabling precise homology-directed repair-mediated gene correction in CF models. Optimized Lung SORT LNPs deliver mRNA to lung basal cells in Ai9 reporter mice. SORT LNP treatment successfully corrected the CFTR mutations in homozygous G542X mice and in patient-derived human bronchial epithelial cells with homozygous F508del mutations, leading to the restoration of CFTR protein expression and chloride transport function. This proof-of-concept study will contribute to accelerating the clinical development of mRNA LNPs for CF treatment through CRISPR/Cas gene correction.

PMID:37951948 | DOI:10.1038/s41467-023-42948-2

J Cyst Fibros. 2023 Nov 9:S1569-1993(23)01669-7. doi: 10.1016/j.jcf.2023.10.019. Online ahead of print.

ABSTRACT

BACKGROUND: There have been dramatic clinical improvements in people with cystic fibrosis (PwCF) commenced on the cystic fibrosis conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (ETI). Sputum proteomics is a powerful research technique capable of identifying important airway disease mechanisms. Using this technique, we evaluated how ETI changes the sputum proteome in PwCF.

METHODS: Sputum samples from 21 CF subjects pre- and post- ETI, 6 CF controls ineligible for ETI, and 15 healthy controls were analysed by liquid chromatography mass spectrometry.

RESULTS: Post-ETI, mean FEV1 % increased by 13.7 % (SD 7.9). Principal component and hierarchical clustering analysis revealed that the post-ETI proteome shifted to an intermediate state that was distinct from pre-ETI and healthy controls, even for those achieving normal lung function. Functional analysis showed incomplete resolution of neutrophilic inflammation. The CF control sputum proteome did not alter. At the protein-level many more proteins increased in abundance than decreased following ETI therapy (80 vs 30; adjusted p value <0.05), including many that have anti-inflammatory properties. Of those proteins that reduced in abundance many were pro-inflammatory neutrophil-derived proteins. Several important respiratory proteases were unchanged.

CONCLUSIONS: Sputum proteomics can provide insights into CF lung disease mechanisms and how they are modified by therapeutic intervention, in this case ETI. This study identifies imbalances in pro- and anti- inflammatory proteins in sputum that partially resolve with ETI even in those achieving normal spirometry values. This post-ETI intermediate state could contribute to ongoing airway damage and therefore its relevance to clinical outcomes needs to be established.

PMID:37951788 | DOI:10.1016/j.jcf.2023.10.019

J Cyst Fibros. 2023 Nov 9:S1569-1993(23)01664-8. doi: 10.1016/j.jcf.2023.10.018. Online ahead of print.

ABSTRACT

BACKGROUND: Little is known about the burden of illness experienced by people with cystic fibrosis (pwCF) since the advent of CF transmembrane conductance regulator (CFTR) modulator therapies. Studies that characterize the nature of illness burden are needed to inform the development and implementation of palliative care programs that can serve this population and address quality of life concerns.

METHODS: Adults with CF treated at five U.S. CF centers were surveyed to obtain baseline data for the Improving Life with CF primary palliative care implementation trial. Consenting patients completed the Integrated Palliative Care Outcome Scale (IPOS), a multidimensional measure of unmet needs for palliative care. Sociodemographic and clinical information was also obtained. The associations among these variables were examined through bivariate and multivariable analyses.

RESULTS: Among 256 adults, the most distressing symptoms included not feeling "at peace", communication difficulties with family/friends, anxiety over illness or its treatment, and a lack of energy. In the multivariable analyses, CFTR modulator use was associated with lower IPOS total and physical symptoms scores; female sex and increased hospitalizations were associated with higher scores. Increased age and history of distal intestinal obstructive syndrome were associated with higher IPOS physical symptoms scores.

CONCLUSIONS: These findings illuminate the nature of illness burden for pwCF in the era of CFTR modulator therapies. Although illness burden is positively affected by modulator therapy, there is a continuing need for palliative care to address physical, emotional, and spiritual distress, and the communication and practical needs experienced by adults with CF.

PMID:37951787 | DOI:10.1016/j.jcf.2023.10.018

Biochem Pharmacol. 2023 Nov 9:115906. doi: 10.1016/j.bcp.2023.115906. Online ahead of print.

ABSTRACT

Burkholderia cenocepacia is an opportunistic respiratory pathogen of particular relevance to patients with cystic fibrosis (CF), primarily regulating its biological functions and virulence factors through two quorum sensing (QS) systems (CepI/R and CciI/R). The highly persistent incidence of multidrug resistant Burkholderia cenocepacia poses a global threat to public health. In this study, we investigated the effects of tyramine, one biogenic amine, on the QS systems of Burkholderia cenocepacia. Genetic and biochemical analyses revealed that tyramine inhibited the production of N-hexanoyl-homoserine (AHL) signaling molecules (C8-HSL and C6-HSL) by blocking the CepI/R and CciI/R systems. As a result, the inhibition of QS systems leads to reduced production of various virulence factors, such as biofilm formation, extracellular polysaccharides, lipase, and swarming motility. Notably, as a potential quorum sensing inhibitor, tyramine exhibits low toxicity in vivo in Galleria mellonella larvae and is well characterized by Lipinski's five rules. It also shows high gastrointestinal absorption and the ability to cross the blood-brain barrier according to SwissADME database and ProTox-II server. Additionally, tyramine was found to enhance the efficacy of tetracycline in reducing the infectivity of Burkholderia cenocepacia in Galleria mellonella larvae infection model. Therefore, tyramine could be a promising candidate for combination therapy with traditional antimicrobials to improve their effectiveness against Burkholderia cenocepacia.

PMID:37951366 | DOI:10.1016/j.bcp.2023.115906

Am J Kidney Dis. 2023 Nov 9:S0272-6386(23)00896-X. doi: 10.1053/j.ajkd.2023.09.011. Online ahead of print.

NO ABSTRACT

PMID:37951339 | DOI:10.1053/j.ajkd.2023.09.011

J Cyst Fibros. 2023 Nov 8:S1569-1993(23)01671-5. doi: 10.1016/j.jcf.2023.10.021. Online ahead of print.

ABSTRACT

BACKGROUND: Our objective was to discover novel urinary biomarkers of antibiotic-associated nephrotoxicity using an ex-vivo human microphysiological system (MPS) and to translate these findings to a prospectively enrolled cystic fibrosis (CF) population receiving aminoglycosides and/or polymyxin E (colistin) for a pulmonary exacerbation.

METHODS: We populated the MPS with primary human kidney proximal tubule epithelial cells (PTECs) from three donors and modeled nephrotoxin injury through exposure to 50 µg/mL polymyxin E for 72 h. We analyzed gene transcriptional responses by RNAseq and tested MPS effluents. We translated candidate biomarkers to a CF cohort via analysis of urine collected prior to, during and two weeks after antibiotics and patients were followed for a median of 3 years after antibiotic use.

RESULTS: Polymyxin E treatment resulted in a statistically significant increase in the pro-apoptotic Fas gene relative to control in RNAseq of MPS: fold-change = 1.63, FDR q-value = 7.29 × 10-5. Effluent analysis demonstrated an acute rise of soluble Fas (sFas) concentrations that correlated with cellular injury. In 16 patients with CF, urinary sFas concentrations were significantly elevated during antibiotic treatment, regardless of development of AKI. Over a median of three years of follow up, we identified seven cases of incident chronic kidney disease (CKD). Urinary sFas concentrations during antibiotic treatment were significantly associated with subsequent development of incident CKD (unadjusted relative risk = 2.02 per doubling of urinary sFas, 95 % CI = 1.40, 2.90, p < 0.001).

CONCLUSIONS: Using an ex-vivo MPS, we identified a novel biomarker of proximal tubule epithelial cell injury, sFas, and translated these findings to a clinical cohort of patients with CF.

PMID:37949747 | DOI:10.1016/j.jcf.2023.10.021

Arch Bronconeumol. 2023 Oct 30:S0300-2896(23)00359-9. doi: 10.1016/j.arbres.2023.10.007. Online ahead of print.

NO ABSTRACT

PMID:37949760 | DOI:10.1016/j.arbres.2023.10.007

J Cyst Fibros. 2023 Nov 8:S1569-1993(23)01662-4. doi: 10.1016/j.jcf.2023.10.014. Online ahead of print.

NO ABSTRACT

PMID:37949746 | DOI:10.1016/j.jcf.2023.10.014

J Cyst Fibros. 2023 Nov 8:S1569-1993(23)01672-7. doi: 10.1016/j.jcf.2023.11.001. Online ahead of print.

ABSTRACT

BACKGROUND: Although cystic fibrosis (CF) standards of care have been produced and regularly updated, they are not specifically targeting at the adult population. The ECFS Standards of Care Project established an international task force of experts to identify quality standards for adults with CF and assess their adherence.

METHODS: This study was composed of two phases. In the first one, a task force of international experts derived from published guidelines and graded ten quality standards for adult CF care using a modified Delphi methodology. In the second phase, an international audit was conducted among adult CF centers to retrospectively validate the quality statements and monitor adherence.

RESULTS: The task force identified 10 quality standards specific to the care of adults with CF, mainly based on the 2018 ECFS standards of care. 14 adult CF centers participated in the audit, which showed that most quality standards for the management of CF in adults are met across Europe. Heterogeneity in adherence to standards was found across centers according to geographical setting and centers' characteristics.

CONCLUSIONS: The identification of quality standards is a valuable resource for the standardization and monitoring of care delivery across centers taking care of adults with CF.

PMID:37949745 | DOI:10.1016/j.jcf.2023.11.001

Eur Respir J. 2023 Nov 9:2202029. doi: 10.1183/13993003.02029-2022. Online ahead of print.

ABSTRACT

AIMS: In two pivotal Phase 3 trials, up to 24 weeks of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in patients with cystic fibrosis ≥12 years of age who have at least one F508del allele. The aim of this study is to assess long-term safety and efficacy of ELX/TEZ/IVA in these patients.

METHODS: In this Phase 3, open-label, single-arm extension study, participants with F508del-minimal function (from a 24-week parent study; n=399) or F508del-F508del (from a 4-week parent study; n=107) genotypes receive ELX/TEZ/IVA at the same dose (ELX 200 mg once daily, TEZ 100 mg once daily and IVA 150 mg every 12 h). The primary endpoint is safety and tolerability. A prespecified interim analysis was conducted when the last participant reached the Week 144 visit.

RESULTS: At the Week 144 interim analysis, mean duration of exposure to ELX/TEZ/IVA in the extension study was 151.1 weeks. Exposure-adjusted rates of adverse events (586.6 events per 100 participant-years) and serious adverse events (22.4 events per 100 participant-years) were lower than in the ELX/TEZ/IVA treatment group in the 24-week parent study (1096.0 events per 100 participant-years and 36.9 events per 100 participant-years, respectively); most participants had adverse events classified as mild (16.4% of participants) or moderate (60.3% of participants) in severity. Fourteen participants (2.8%) had adverse events that led to treatment discontinuation. Following initiation of ELX/TEZ/IVA, participants had increases in per cent predicted FEV1 (ppFEV1), Cystic Fibrosis Questionnaire-Revised respiratory domain score and body mass index, and had decreases in sweat chloride concentration and pulmonary exacerbations rates that were maintained over the interim analysis period. The mean annualised rate of change in ppFEV1 was +0.07 percentage points (95% CI, -0.12 to 0.26) among the participants.

CONCLUSIONS: ELX/TEZ/IVA was generally safe and well-tolerated, with a safety profile consistent with the 24-week parent study. Participants had sustained improvements in lung function, respiratory symptoms, CFTR function, pulmonary exacerbation rates and nutritional status. These results support the favourable safety profile and durable, disease-modifying clinical benefits of ELX/TEZ/IVA.

PMID:37945033 | DOI:10.1183/13993003.02029-2022

J Pediatr Psychol. 2023 Nov 7:jsad076. doi: 10.1093/jpepsy/jsad076. Online ahead of print.

ABSTRACT

OBJECTIVE: Nutrition and weight gain significantly contribute to overall health outcomes in children with cystic fibrosis (CF). Strong emphasis is placed on these entities by the CF team, which can cause stress for parents and impact parent and child mealtime behaviors. The current study sought to investigate the relationship between parental feeding style, parenting stress, and parent and child mealtime behaviors in families of children with CF.

METHODS: Forty-five parents of a child with CF between the ages of 2 and 10 years were recruited during a CF clinic appointment. They completed surveys assessing child mealtime behaviors, parental feeding style, and parental stress. Medical data including body mass index (BMI) were collected from the medical record.

RESULTS: There was a significant difference in behavioral feeding scores based on feeding style (F3,41 = 13.48, p <.001), with authoritarian parents reporting significantly greater mealtime behavior problems than all other parents. There was also a significant difference in parenting stress based on parental feeding style (F3,41=4.11, p <.05), with authoritarian parents showing more stress than authoritative parents (Mdiff=23.70, p <.05). Correlation analyses showed a positive relationship between behavioral feeding problems and parent stress, r(45)=0.403; p <.01.

CONCLUSIONS: Data suggest parents using an authoritarian feeding style experience more stress and behavioral feeding problems than other parents. More feeding problems were also associated with more stress. Findings help determine how pediatric psychologists can intervene to support positive parenting behaviors that reduce children's mealtime behavior problems and parental stress, thus improving health outcomes in this vulnerable population.

PMID:37944096 | DOI:10.1093/jpepsy/jsad076

Microbiology (Reading). 2023 Nov;169(11). doi: 10.1099/mic.0.001396.

NO ABSTRACT

PMID:37943284 | DOI:10.1099/mic.0.001396

J Virol. 2023 Nov 9:e0085023. doi: 10.1128/jvi.00850-23. Online ahead of print.

ABSTRACT

The Burkholderia cepacia complex (Bcc) causes life-threatening respiratory tract infections in persons with cystic fibrosis (CF). In CF patients, end-stage pulmonary disease often requires lung transplantation, and pre-transplant colonization with antibiotic-resistant Burkholderia is predictive of poor post-transplant outcomes. To address this issue, phage therapy has been proposed as a treatment for these infections. However, the majority of characterized Bcc phages are temperate and are therefore difficult to use as therapeutics, and the few obligately lytic phages that have been isolated have limited host ranges. To overcome these limitations, we have produced a virulent, broad-host range derivative of the temperate Burkholderia cenocepacia phage Milagro. Phage Milagro is a 39.1-kb temperate myophage related to phage KL3 and the paradigm coliphage P2. This phage showed a phenotype of spontaneous autoplaquing on lawns of Milagro lysogens, and these autoplaques were found to be produced by virulent mutants of the parental phage Milagro. Mutations associated with virulence were identified as single base changes, insertions or deletions in the phage lysogeny control region that define potential operator sites required for lysogen maintenance. To improve phage host range, the C-terminal domain of the Milagro tail fiber was replaced with the receptor-binding domain of the broad-host range tailocin (high molecular weight bacteriocin) BceTMilo. A spontaneous virulent mutant of this engineered phage, designated Milagro vir gp20:Milo, exhibited an expanded host range over the parental phage and is able to infect multiple Bcc species including B. cenocepacia, Burkholderia multivorans, Burkholderia gladioli, Burkholderia dolosa, and Burkholderia vietnamensis.IMPORTANCEBurkholderia infections are a significant concern in people with CF and other immunocompromising disorders, and are difficult to treat with conventional antibiotics due to their inherent drug resistance. Bacteriophages, or bacterial viruses, are now seen as a potential alternative therapy for these infections, but most of the naturally occurring phages are temperate and have narrow host ranges, which limit their utility as therapeutics. Here we describe the temperate Burkholderia phage Milagro and our efforts to engineer this phage into a potential therapeutic by expanding the phage host range and selecting for phage mutants that are strictly virulent. This approach may be used to generate new therapeutic agents for treating intractable infections in CF patients.

PMID:37943040 | DOI:10.1128/jvi.00850-23

Cochrane Database Syst Rev. 2023 Nov 9;11:CD007639. doi: 10.1002/14651858.CD007639.pub3.

ABSTRACT

BACKGROUND: Nebuliser systems are used to deliver medications to the lungs, to control the symptoms and the progression of lung disease in people with cystic fibrosis (CF). There are many different nebulised-medications prescribed for people with CF and there are many different types of nebuliser systems. Some of these nebulised medications are licenced for, and can be taken via only one type of nebuliser system; some are licensed for, and can be taken via more than one type of nebuliser system. This is an update to a previous systematic review.

OBJECTIVES: To assess the time efficiency, effectiveness, safety, cost and impact of use (e.g. burden of care, adherence, quality of life (QoL)) of different nebuliser systems, when used with different inhaled medications for people with CF.

SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books containing conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. We also searched online trial registries. Date of the most recent search: 9 August 2023.

SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing nebuliser systems, including conventional nebulisers, vibrating mesh technology (VMT) systems, adaptive aerosol delivery (AAD) systems and ultrasonic nebuliser systems.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third review author assessed studies where agreement could not be reached. They assessed the certainty of the evidence using GRADE.

MAIN RESULTS: The search identified 216 studies with 33 of these (2270 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic saline and other solutions through the different nebuliser systems in children and adults with CF. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. The certainty of the evidence ranged from low to very low. Some conventional nebuliser systems providing higher flows, higher respirable fractions, and smaller particles decrease treatment time, increase deposition (the amount of drug reaching the lung), and may be preferred by people with CF, as compared to other conventional nebuliser systems providing lower flows, lower respirable fractions and larger particles. Newer nebuliser systems using AAD, or VMT (or both) reduce treatment time compared to conventional systems. Deposition (as a percentage of priming dose) with AAD is greater than with conventional systems. VMT systems may give greater deposition than conventional systems when measuring sputum levels. The available data indicate that these newer systems are safe when used with an appropriate priming dose, which may be different to the priming dose used for conventional systems. There is an indication that adherence is maintained or improved and that individuals prefer AAD or VMT systems, but also that some nebuliser systems using VMT may be subject to increased system failures. There is limited, unclear evidence on the impact of different nebuliser systems on lung function and a lack of data on the impact of different nebuliser systems on our outcomes of quality of life (QoL), adverse effects, respiratory exacerbations and related implications, adherence, satisfaction, cost and device reliability.

AUTHORS' CONCLUSIONS: Newer technologies e.g. AAD and VMT have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, preference and adherence. Data are lacking for all varieties of medications which are used in CF care, including different inhaled antibiotics or hypertonic saline, with all delivery (nebuliser system) possibilities. Long-term RCTs are needed to evaluate different nebuliser systems to determine patient-focused outcomes (such as QoL and burden of care), safe and effective dosing levels of a wide variety of medications, clinical outcomes (such as hospitalisations and need for antibiotics), and an economic evaluation of their use. There are insufficient data to establish whether one nebuliser system is better than another overall. Clinicians should be aware of the variability in the performance of different nebuliser systems, compatibility with specific nebulised medication, and they must work with their patients to choose the best nebuliser system for each individual. This is likely to be an ongoing process as the needs and circumstances of each individual change over time.

PMID:37942828 | DOI:10.1002/14651858.CD007639.pub3

Microbiology (Reading). 2023 Nov;169(11). doi: 10.1099/mic.0.001408.

ABSTRACT

Stenotrophomonas maltophilia is a Gram-negative emerging opportunistic pathogen often present in people with respiratory diseases such as cystic fibrosis (CF). People with CF (pwCF) experience lifelong polymicrobial infections of the respiratory mucosa. Our prior work showed that Pseudomonas aeruginosa promotes persistence of S. maltophilia in mouse respiratory infections. As is typical for environmental opportunistic pathogens, S. maltophilia has a large genome and a high degree of genetic diversity. In this study, we evaluated the genomic content of S. maltophilia, combining short and long read sequencing to construct nearly complete genomes of 10 clinical isolates. The genomes of these isolates were then compared with all publicly available S. maltophilia genome assemblies, and each isolate was then evaluated for colonization/persistence in vivo, both alone and in coinfection with P. aeruginosa. We found that while the overall genome size and GC content were fairly consistent between strains, there was considerable variability in both genome structure and gene content. Similarly, there was significant variability in S. maltophilia colonization and persistence in experimental mouse respiratory infections in the presence or absence of P. aeruginosa. Ultimately, this study gives us a greater understanding of the genomic diversity of clinical S. maltophilia isolates, and how this genomic diversity relates to both interactions with other pulmonary pathogens and to host disease progression. Identifying the molecular determinants of infection with S. maltophilia can facilitate development of novel antimicrobial strategies for a highly drug-resistant pathogen.

PMID:37942787 | DOI:10.1099/mic.0.001408

Cureus. 2023 Oct 8;15(10):e46666. doi: 10.7759/cureus.46666. eCollection 2023 Oct.

ABSTRACT

Allergic bronchopulmonary aspergillosis (ABPA) is a notable complication in patients with chronic lung diseases, such as chronic bronchial asthma and cystic fibrosis, presenting challenges in diagnosis and management. ABPA is an allergic response to multiple antigens expressed by Aspergillus fumigatus in the lung mucosa, resulting in airway inflammation and damage. This study discusses a 58-year-old male patient with a history of longstanding bronchial asthma for 28 years who presented with worsening respiratory symptoms. The patient's blood investigations showed peripheral eosinophilia, increased total serum immunoglobulin IgE, and positive Aspergillus serology. Bronchoalveolar lavage samples showed a significant increase in Aspergillus antigens, along with positive radiological findings, leading to the diagnosis of ABPA. He was successfully treated with a combination of dual antifungal therapy, systemic corticosteroids, inhaled corticosteroids, and bronchodilators. This study emphasizes the importance of considering ABPA in patients with chronic bronchial asthma experiencing deteriorating respiratory symptoms and highlights the significance of a multidisciplinary approach for accurate diagnosis and effective management of this condition.

PMID:37942376 | PMC:PMC10628675 | DOI:10.7759/cureus.46666