Pediatr Pulmonol. 2023 Oct 16. doi: 10.1002/ppul.26709. Online ahead of print.

ABSTRACT

BACKGROUND: Structural lung changes seen on computed tomography (CT) scans in persons with primary ciliary dyskinesia (pwPCD) are currently described using cystic fibrosis (CF) derived scoring systems. Recent work has shown structural changes and frequencies that are unique to PCD, indicating the need for a unique PCD-derived scoring system.

METHODS: Chest CT scans from 30 pwPCD, were described for structural changes including bronchiectasis, bronchial wall thickening, mucous plugging, atelectasis, air trapping, and interlobar septal thickening and, additionally, changes previously described as being frequent in pwPCD including extensive tree-in-bud pattern of mucous plugging, bronchoceles or nodules, thickening of interlobar and interlobular septa and whole lobe atelectasis. Based on these findings a novel and unique scoring system, the Specific PCD Evaluation by CT (SPEC) score was constructed. Scans were then re-scored using the SPEC score and results compared to corresponding measurements of lung function to assess structure-function correlation.

RESULTS: Total SPEC scores ranged from 0 to 60 (max possible score 90). There was a strong negative correlation between the SPEC score (SPEC) and forced vital capacity (FVC), forced expiratory volume over 1 s (FEV1 ) and FEV1 /FVC ratio (-r = .784, -.865, -.872 respectively).

CONCLUSIONS: Using PCD-derived data we describe the construct of a PCD-specific score for assessing lung structural damage on CT scans, the SPEC score. A strong correlation between the SPEC score and PFT variables was identified. The SPEC score holds the potential for describing longitudinal changes in CT scans and assessing the efficacy of interventive therapies in patients with PCD.

PMID:37842974 | DOI:10.1002/ppul.26709

Cureus. 2023 Sep 13;15(9):e45186. doi: 10.7759/cureus.45186. eCollection 2023 Sep.

ABSTRACT

Cystic fibrosis (CF) is a multiorgan disease, caused by autosomal recessive (AR) mutations in the cystic fibrosis transmembrane regulator (CFTR) acting primarily as a chloride channel. CF is most commonly diagnosed in Caucasian populations. Common clinical presentations in pediatric patients include chronic cough, respiratory tract infections such as pneumonia, digestive symptoms, and stunted growth, and malnutrition due to gastrointestinal malabsorption and pancreatic insufficiency. Excessive sweat sodium chloride losses due to dysfunctional sweat glands in CFTR result in volume contraction and secondary hyperaldosteronism leading to renal potassium losses and metabolic alkalosis. Hypokalemic hypochloremic metabolic alkalosis is a known but uncommon presenting sign of the disease, documented as pseudo Bartter syndrome. Common mutations in the CFTR gene are now included in prenatal genetic screening programs. We describe the case of an infant of African descent with normal prenatal screening who presented with severe hypokalemic hypochloremic metabolic alkalosis and was diagnosed with CF with further genetic confirmation of the diagnosis.

PMID:37842418 | PMC:PMC10575793 | DOI:10.7759/cureus.45186

Front Pharmacol. 2023 Sep 28;14:1236550. doi: 10.3389/fphar.2023.1236550. eCollection 2023.

ABSTRACT

Asthma is one of the main non-communicable chronic diseases and affects a huge portion of the population. It is a multifactorial disease, classified into several phenotypes, being the allergic the most frequent. The pathophysiological mechanism of asthma involves a Th2-type immune response, with high concentrations of allergen-specific immunoglobulin E, eosinophilia, hyperreactivity and airway remodeling. These mechanisms are orchestrated by intracellular signaling from effector cells, such as lymphocytes and eosinophils. Ion channels play a fundamental role in maintaining the inflammatory response on asthma. In particular, transient receptor potential (TRP), stock-operated Ca2+ channels (SOCs), Ca2+-activated K+ channels (IKCa and BKCa), calcium-activated chloride channel (TMEM16A), cystic fibrosis transmembrane conductance regulator (CFTR), piezo-type mechanosensitive ion channel component 1 (PIEZO1) and purinergic P2X receptor (P2X). The recognition of the participation of these channels in the pathological process of asthma is important, as they become pharmacological targets for the discovery of new drugs and/or pharmacological tools that effectively help the pharmacotherapeutic follow-up of this disease, as well as the more specific mechanisms involved in worsening asthma.

PMID:37841931 | PMC:PMC10568497 | DOI:10.3389/fphar.2023.1236550

Res Sq. 2023 Sep 25:rs.3.rs-3356170. doi: 10.21203/rs.3.rs-3356170/v1. Preprint.

ABSTRACT

Background Cystic fibrosis (CF) is a genetic disorder causing poor mucociliary clearance in the airways and subsequent respiratory infection. The recently approved triple therapy Elexacaftor-Tezacaftor-Ivacaftor (ETI) has significantly improved the lung function and decreased airway infection of persons with CF (pwCF). This improvement has been shown to occur rapidly, within the first few weeks of treatment. The effects of longer term ETI therapy on lung infection dynamics, however, remains mostly unknown. Results Here, we applied 16S rRNA gene amplicon sequencing, untargeted metabolomics, and neutral models to high-resolution, longitudinally collected sputum samples from pwCF on ETI therapy (162 samples, 7 patients) and compared to similarly collected data set of CF subjects not taking ETI (630 samples, 9 patients). Because ETI reduces sputum production, samples were collected in freezers provided in the subject's homes at least 3 months after first taking ETI, with those on ETI collecting a sample approximately weekly. The lung function (%ppFEV1) of those in our longitudinal cohort significantly improved after ETI (6.91, SD = 7.74), indicating our study cohort was responsive to ETI. The daily variation of alpha- and beta-diversity of both the microbiome and metabolome was higher for those on ETI, reflecting a more dynamic microbial community and chemical environment during treatment. Four of the seven subjects on ETI were persistently infected with Pseudomonas or Burkholderia in their sputum throughout the sampling period. The microbiome and metabolome dynamics on ETI were personalized, where some subjects had a progressive change with time on therapy, whereas others had no association with time on treatment. To further classify the augmented variance of the CF microbiome under therapy, we fit the microbiome data to a Hubbell neutral dynamics model in a patient-stratified manner and found that the subjects on ETI had better fit to a neutral model. Conclusion This study shows that the longitudinal microbiology and chemistry in airway secretions from subjects on ETI has become more dynamic and neutral, and that after the initial improvement in lung function, many are still persistently infected with CF pathogens.

PMID:37841851 | PMC:PMC10571617 | DOI:10.21203/rs.3.rs-3356170/v1

Environ Epidemiol. 2023 Aug 25;7(5):e266. doi: 10.1097/EE9.0000000000000266. eCollection 2023 Oct.

ABSTRACT

RATIONALE: The prevalence of nontuberculous mycobacterial (NTM) pulmonary disease varies geographically in the United States. Previous studies indicate that the presence of certain water-quality constituents in source water increases NTM infection risk.

OBJECTIVE: To identify water-quality constituents that influence the risk of NTM pulmonary infection in persons with cystic fibrosis in the United States.

METHODS: We conducted a population-based case-control study using NTM incidence data collected from the Cystic Fibrosis Foundation Patient Registry during 2010-2019. We linked patient zip code to the county and associated patient county of residence with surface water data extracted from the Water Quality Portal. We used logistic regression models to estimate the odds of NTM infection as a function of water-quality constituents. We modeled two outcomes: pulmonary infection due to Mycobacterium avium complex (MAC) and Mycobacterium abscessus species.

RESULTS: We identified 484 MAC cases, 222 M. abscessus cases and 2816 NTM-negative cystic fibrosis controls resident in 11 states. In multivariable models, we found that for every 1-standardized unit increase in the log concentration of sulfate and vanadium in surface water at the county level, the odds of infection increased by 39% and 21%, respectively, among persons with cystic fibrosis with MAC compared with cystic fibrosis-NTM-negative controls. When modeling M. abscessus as the dependent variable, every 1-standardized unit increase in the log concentration of molybdenum increased the odds of infection by 36%.

CONCLUSIONS: These findings suggest that naturally occurring and anthropogenic water-quality constituents may influence the NTM abundance in water sources that supply municipal water systems, thereby increasing MAC and M. abscessus infection risk.

PMID:37840858 | PMC:PMC10569765 | DOI:10.1097/EE9.0000000000000266

Neurol Clin Pract. 2023 Oct;13(5):e200188. doi: 10.1212/CPJ.0000000000200188. Epub 2023 Aug 17.

ABSTRACT

BACKGROUND AND OBJECTIVES: The prevalence of generalized joint hypermobility (GJH) is 5-65% in children and adolescents. The hypothesis of this study was to see whether there is an association between headache characteristics and GJH in children and adolescents with migraine.

METHODS: We performed a primary retrospective case-control analysis of an established database of patients with headache aged 5-17 years.

RESULTS: We included 5435 participants. Approximately 31.6% of participants (1,719/5,435) were diagnosed with GJH (Beighton score ≥ 6). Nausea (73.1% vs 67.5%, χ2 with 1 degree of freedom = 17.0, p < 0.0001), phonophobia (87.3% vs 78.8%, χ2 with 1 degree of freedom = 18.0, p < 0.0001), and the PedMIDAS score (48.2 ± 52.5, 95% CI 45.7-50.6 vs 41.6 ± 51.2, 95% CI 40.0-43.3, effect size = 0.13, p < 0.0001) were noted to be more severe in participants with GJH than those without GJH.

DISCUSSION: Youths with GJH and migraine were noted to have more severe migraine characteristics.

PMID:37840826 | PMC:PMC10573031 | DOI:10.1212/CPJ.0000000000200188

J Cyst Fibros. 2023 Oct 13:S1569-1993(23)00925-6. doi: 10.1016/j.jcf.2023.10.005. Online ahead of print.

ABSTRACT

PURPOSE: Inadequate participation of Adolescents and Young Adults (AYAs) and parents are well-established barriers of transition. Shifts in roles are mandatory with increasing responsibilities for AYAs and decreasing involvement of parents in care. This study explores the shifts in roles of AYAs and their parents and its association with the subjective experience of transition.

METHODS: We conducted in-depth semi-structured interviews with AYAs living with Cystic Fibrosis and parents. Participants were recruited through patient organizations via convenience sampling and questioned on which roles they assumed during transition. Three authors performed an interpretative phenomenological analysis, establishing separate code trees for AYAs and parents. Data saturation was achieved.

RESULTS: 18 AYAs (age 21y±2.9) and 14 parents (age 50y±2.0) were included. We identified five common themes: (1) the reciprocal reliance between AYAs and parents, (2) the policies of physicians and hospitals, (3) the AYAs' changing appeal and need for support, (4) the identification of parents as co-patients, and (5) the enforced changes in the roles of parents. AYAs primarily addressed roles related to self-management, while parents discussed family functioning.

CONCLUSIONS: This study identified motives underlying the assumption of roles by AYAs and parents. Both AYAs and parents addressed similar themes, highlighting their mutual challenges and needs. In contrast to AYAs, parents' desired roles were undefined and a latent sense of responsibility was identified as an important motive. Healthcare providers should acknowledge parents' challenging position and communicate transparently about changing roles. Additionally, healthcare providers should recognize that imposing restrictive roles may result in parental resistance, but can also foster AYAs' skill development. Future research should examine the short- and long-term impact of role-management interventions in AYAs and their parents.

PMID:37839982 | DOI:10.1016/j.jcf.2023.10.005

Int J Antimicrob Agents. 2023 Oct 13:107001. doi: 10.1016/j.ijantimicag.2023.107001. Online ahead of print.

ABSTRACT

The aim of the project was the development and characterization of powders containing a probiotic (Lpb. plantarum, Lcb. rhamnosus or L. acidophilus) to be administered to the lung for the containment of pathogens growth in patients with cystic fibrosis. The optimized spray drying process for the powder manufacturing was able to preserve viability of the bacteria which decreased of only one Log unit and it was maintained up to 30 days. Probiotic powders showed a high respirability (42-50% of particles had a size <5 µm) suitable for lung deposition and were proven safe on A549 and Calu-3 cells up to a concentration of 107 CFU/mL. The Lpb. plantarum adhesion to both cell lines tested was at least 10%. Surprisingly, Lpb. plantarum powder was bactericidal at a concentration of 106 CFU/mL on P. aeruginosa while the other two strains were bacteriostatic. The work represents a promising starting point to consider a probiotic inhalation powder a value in keeping the growth of pathogenic microflora in check during the antibiotic inhalation therapy suspension in cystic fibrosis treatment regimen. This approach could also be advantageous for interfering competitively with pathogenic bacteria and promoting the restoration of the healthy microbiota.

PMID:37839715 | DOI:10.1016/j.ijantimicag.2023.107001

Med J Aust. 2023 Oct 15. doi: 10.5694/mja2.52119. Online ahead of print.

ABSTRACT

Cystic fibrosis is a monogenic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which transports chloride ions in secretory organs. Modulator therapies are small molecules that correct CFTR dysfunction and can lead to a wide range of benefits for both pulmonary and extrapulmonary complications of cystic fibrosis. With advancements in airway, antimicrobial and nutritional therapies and now introduction of modulator therapies, most people living with cystic fibrosis in Australia are now adults. For adults with cystic fibrosis, endocrine manifestations such as cystic fibrosis-related diabetes, metabolic bone disease, and reproductive health are becoming increasingly important, and emerging evidence on the endocrine effects of CFTR modulator therapies is promising and is shifting paradigms in our understanding and management of these conditions. The management of cystic fibrosis-related diabetes will likely need to pivot for high responders to modulator therapy with dietary adaptions and potential use of medications traditionally reserved for adults with type 2 diabetes, but evidence to support changing clinical care needs is currently lacking. Increased attention to diabetes-related complications screening will also be required. Increased exercise capacity due to improved lung function, nutrition and potentially direct modulator effect may have a positive impact on cystic fibrosis-related bone disease, but supporting evidence to date is limited. Fertility can improve in women with cystic fibrosis taking modulator therapy. This has important implications for pregnancy and lactation, but evidence is lacking to guide pre-conception and antenatal management. Provision of multidisciplinary clinical care remains ever-important to ensure the emergence of endocrine and metabolic complications are optimised in adults with cystic fibrosis.

PMID:37839059 | DOI:10.5694/mja2.52119

Lipids Health Dis. 2023 Oct 14;22(1):172. doi: 10.1186/s12944-023-01937-6.

ABSTRACT

Mead acid (MA, 5,8,11-eicosatrienoic acid) is an n-9 polyunsaturated fatty acid (PUFA) and a marker of essential fatty acid deficiency, but nonetheless generally draws little attention. MA is distributed in various normal tissues and can be converted to several specific lipid mediators by lipoxygenase and cyclooxygenase. Recent pathological and epidemiological studies on MA raise the possibility of its effects on inflammation, cancer, dermatitis and cystic fibrosis, suggesting it is an endogenous multifunctional PUFA. This review summarizes the biosynthesis, presence, metabolism and physiological roles of MA and its relation to various diseases, as well as the significance of MA in PUFA metabolism.

PMID:37838679 | DOI:10.1186/s12944-023-01937-6

J Cyst Fibros. 2023 Oct 12:S1569-1993(23)00930-X. doi: 10.1016/j.jcf.2023.10.007. Online ahead of print.

ABSTRACT

BACKGROUND: No evidence exists to guide the frequency of obtaining bacterial respiratory cultures during inpatient treatment of pediatric cystic fibrosis (CF) pulmonary exacerbations (PEx). At our institution, admission and weekly respiratory cultures are routinely collected to guide antimicrobial selection. This study evaluates the extent that this practice informs clinical management and the healthcare-related costs associated with routinely repeating cultures.

METHODS: All children with CF with at least one hospital admission for IV antibiotics from January 2015 to December 2019 were included. Data collected included patient demographics, culture results, and antibiotic history. Respiratory cultures were numbered from the last clinic culture (`Culture 1'), culture on admission (`Culture 2'), and so on (`Cultures 3-6'). Outcomes assessed were microbiological results, frequency and timing of antibiotic change, and total microbiological laboratory costs.

RESULTS: Seventy-eight children with 224 admissions and 695 bacterial cultures were analyzed. Repeated microbiology sampling revealed 118 new bacterial species in 82 admissions. Culture 2 was most likely to identify a new bacterial species (91/115, 79.1 %) and most likely to be followed by a change in antibiotic (33/37; 89.2 %). The total cost of all cultures was $18,264.79. Eliminating Cultures 3-6 from routine practice could represent a 51 % cost-savings ($9,362.89), without significant impact on identification of new clinically relevant isolates.

CONCLUSION: Ongoing bacterial surveillance during a CF PEx beyond admission culture provides minimal information, rarely impacts clinical management, and can increase healthcare costs. An optimized approach would be to routinely obtain admission cultures and to obtain further cultures only if clinically indicated.

PMID:37838488 | DOI:10.1016/j.jcf.2023.10.007

J Cyst Fibros. 2023 Oct 12:S1569-1993(23)00927-X. doi: 10.1016/j.jcf.2023.10.008. Online ahead of print.

NO ABSTRACT

PMID:37838487 | DOI:10.1016/j.jcf.2023.10.008

J Cyst Fibros. 2023 Oct 12:S1569-1993(23)00923-2. doi: 10.1016/j.jcf.2023.10.002. Online ahead of print.

ABSTRACT

Risk of cardiovascular disease (CVD) may be changing in people with cystic fibrosis (pwCF) with widespread use of highly effective modulator therapy (HEMT). We performed a retrospective analysis of patients who had lipids checked before and after initiation of ivacaftor or elexacaftor/tezacaftor/ivacaftor. We hypothesized that HEMT negatively impacts lipids (total cholesterol [TC], low-density lipoprotein [LDL], high-density lipoprotein [HDL], TC/HDL ratio). 41 adult patients were included. Paired t-tests showed statistically significant increases in TC (mean difference 16.3 mg/dL, p = 0.007, n = 40), LDL (mean difference 17.1 mg/dL, p < 0.001, n = 35), and TC/HDL ratio (mean difference 0.40, p = 0.014, n = 39) after HEMT initiation. HDL was unchanged (mean difference -1.5 mg/dL, p = 0.69, n = 39). Linear mixed models showed CF liver disease was associated with significantly blunted changes in TC and LDL. Family history of CVD risk factors was associated with significantly accentuated increases in TC and LDL. These data suggest a role for more lipid screening in pwCF.

PMID:37838486 | DOI:10.1016/j.jcf.2023.10.002

Int Forum Allergy Rhinol. 2023 Oct 14. doi: 10.1002/alr.23288. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic rhinosinusitis (CRS) is common in individuals with cystic fibrosis (CF) and is marked by chronic inflammation and episodes of infection that negatively impact quality of life. Several studies have shown that elexacaftor-tezacaftor-ivacaftor (ETI) improves symptoms and examination findings in CF-CRS. The current study determines the effect of ETI on the sinonasal microbiota in CF.

METHODS: Sinonasal samples were collected under endoscopic visualization before and after starting ETI. Samples were subjected to 16S amplicon sequencing and sequences were processed with the QIIME2 pipeline with subsequent analysis using the vegan R-package.

RESULTS: Twenty-nine individual baseline samples and 23 sample pairs pre-/post-ETI were available. At baseline, the cohort had samples dominated by Staphylococcus, and alpha diversity was lower than that of a published reference set of individuals without sinonasal disease. Individuals with prior sinus surgery had lower alpha diversity as measured by Shannon Index, Observed Richness, and Faith's phylogenetic diversity Index. Beta diversity differed between individuals with and without allergic rhinitis, with higher Staphylococcus abundance in those with allergic rhinitis. No change in alpha or beta diversity was seen after a median of 9 months on ETI. With ETI, the Pseudomonas genus and the genus containing Burkholderia decreased in samples containing these taxa at baseline. Pseudomonas abundance decreased with treatment as measured by qPCR. Core sinonasal microbiome members Staphylococcus, Corynebacterium, and Streptococcus were unchanged, while Moraxella increased with ETI.

CONCLUSIONS: Treatment with ETI leads to a reduction in Pseudomonas abundance within the sinonasal microbiome of individuals with Pseudomonas at baseline.

PMID:37837613 | DOI:10.1002/alr.23288

Nutrients. 2023 Sep 25;15(19):4142. doi: 10.3390/nu15194142.

ABSTRACT

This review article aims to summarize the literature findings regarding the role of micronutrients in children with lung disease. The nutritional and respiratory statuses of critically ill children are interrelated, and malnutrition is commonly associated with respiratory failure. The most recent nutrition support guidelines for critically ill children have recommended an adequate macronutrient intake in the first week of admission due to its association with good outcomes. In children with lung disease, it is important not to exceed the proportion of carbohydrates in the diet to avoid increased carbon dioxide production and increased work of breathing, which potentially could delay the weaning of the ventilator. Indirect calorimetry can guide the process of estimating adequate caloric intake and adjusting the proportion of carbohydrates in the diet based on the results of the respiratory quotient. Micronutrients, including vitamins, trace elements, and others, have been shown to play a role in the structure and function of the immune system, antioxidant properties, and the production of antimicrobial proteins supporting the defense mechanisms against infections. Sufficient levels of micronutrients and adequate supplementation have been associated with better outcomes in children with lung diseases, including pneumonia, cystic fibrosis, asthma, bronchiolitis, and acute respiratory failure.

PMID:37836425 | DOI:10.3390/nu15194142

Diagnostics (Basel). 2023 Sep 29;13(19):3098. doi: 10.3390/diagnostics13193098.

ABSTRACT

To address unmet treatment needs in cystic fibrosis (CF), preclinical and clinical studies are warranted. Because it directly reflects the function of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR), the nasal potential difference test (nPD) can not only be used as a reliable diagnostic test for CF but also to assess efficacy of experimental treatments. We performed a full comprehensive systematic review of the effect of CF treatments on the nPD compared to control conditions tested in separate groups of animal and human subjects. Our review followed a preregistered protocol. We included 34 references: 20 describing mouse studies, 12 describing human studies, and 2 describing both. We provide a comprehensive list of these studies, which assessed the effects of antibiotics, bone marrow transplant, CFTR protein, CFTR RNA, directly and indirectly CFTR-targeting drugs, non-viral and viral gene transfer, and other treatments. Our results support the nPD representing a reliable method for testing treatment effects in both animal models and human patients, as well as for diagnosing CF. However, we also observed the need for improved reporting to ensure reproducibility of the experiments and quantitative comparability of the results within and between species (e.g., with meta-analyses). Currently, data gaps warrant further primary studies.

PMID:37835841 | DOI:10.3390/diagnostics13193098

Int J Mol Sci. 2023 Sep 26;24(19):14592. doi: 10.3390/ijms241914592.

ABSTRACT

The recovery of cells after tissue and organ injury is a complex process [...].

PMID:37834040 | DOI:10.3390/ijms241914592

Int J Mol Sci. 2023 Sep 26;24(19):14539. doi: 10.3390/ijms241914539.

ABSTRACT

Cystic fibrosis (CF) is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. The combination of the CFTR modulators elexacaftor, tezacaftor, and ivacaftor (ETI) enables the effective rescue of CFTR function in people with the most prevalent F508del mutation. However, the functional restoration of rare CFTR variants remains unclear. Here, we use patient-derived intestinal organoids (PDIOs) to identify rare CFTR variants and potentially individuals with CF that might benefit from ETI. First, steady-state lumen area (SLA) measurements were taken to assess CFTR function and compare it to the level observed in healthy controls. Secondly, the forskolin-induced swelling (FIS) assay was performed to measure CFTR rescue within a lower function range, and to further compare it to ETI-mediated CFTR rescue in CFTR genotypes that have received market approval. ETI responses in 30 PDIOs harboring the F508del mutation served as reference for ETI responses of 22 PDIOs with genotypes that are not currently eligible for CFTR modulator treatment, following European Medicine Agency (EMA) and/or U.S. Food and Drug Administration (FDA) regulations. Our data expand previous datasets showing a correlation between in vitro CFTR rescue in organoids and corresponding in vivo ppFEV1 improvement upon a CFTR modulator treatment in published clinical trials, and suggests that the majority of individuals with rare CFTR variants could benefit from ETI. CFTR restoration was further confirmed on protein levels using Western blot. Our data support that CFTR function measurements in PDIOs with rare CFTR genotypes can help to select potential responders to ETI, and suggest that regulatory authorities need to consider providing access to treatment based on the principle of equality for people with CF who do not have access to treatment.

PMID:37833986 | DOI:10.3390/ijms241914539

J Cyst Fibros. 2023 Oct 11:S1569-1993(23)00924-4. doi: 10.1016/j.jcf.2023.10.003. Online ahead of print.

ABSTRACT

BACKGROUND: People with cystic fibrosis (CF) are increasingly considering their reproductive goals. We developed MyVoice:CF, a web-based patient-centered reproductive decision support tool and assessed its implementation in CF care.

METHODS: We conducted a feasibility trial among 18-44-year-old women with CF and multidisciplinary CF providers. Prior to CF clinic visit, patient participants completed a baseline survey, used MyVoice:CF, and assessed acceptability, appropriateness, and usability. After clinic, participants rated impact on reproductive health communication. At 3 months post-use, participants assessed impact on reproductive health outcomes. Provider participants completed a survey and focus group regarding MyVoice:CF feasibility/implementation. We assessed outcomes descriptively. We compared MyVoice:CF's impact on outcomes from baseline to follow-up using McNemar's and Wilcoxon signed rank tests as appropriate.

RESULTS: Forty-three patient participants completed baseline surveys and 40 rated MyVoice:CF's feasibility; 10 providers participated. Patient participants rated MyVoice:CF's acceptability as 4.48±0.50 out of 5, appropriateness as 4.61±0.48 out of 5, and usability as 82.25±11.02 ('A'/excellent). After MyVoice:CF use, participants reported improved reproductive health communication self-efficacy vs. baseline (3.54±1.17vs.3.95±0.93, p<0.001). At baseline, 36% of participants reported any discussion of reproductive goals/plans with their CF team in the past year compared to 59% after first visit post-MyVoice:CF use (p=0.049). Provider participants similarly rated MyVoice:CF as feasible and reported no negative impacts on clinic flow after implementation.

CONCLUSIONS: MyVoice:CF is acceptable, appropriate, and usable for those with CF. Preliminary effectiveness evaluation suggests that MyVoice:CF improves self-efficacy in and frequency of reproductive health communication. Future studies should further assess MyVoice:CF's impact on reproductive health communication and outcomes.

PMID:37833123 | DOI:10.1016/j.jcf.2023.10.003

Infect Genet Evol. 2023 Oct 11:105513. doi: 10.1016/j.meegid.2023.105513. Online ahead of print.

ABSTRACT

In cystic fibrosis (CF), Pseudomonas aeruginosa (Pa) is a major pathogen that can persistently colonize patients. Genetic studies showed a high diversity of Pa, the success of widespread or 'international' clones and described epidemic clones in CF and Epidemic High-Risk (ERH) clones. Here, we characterized Pa genetic diversity over time after first colonization in CF patients, with the aim of accurately describing the dynamics of colonization in a context of scarce longitudinal studies. Results represent the first genotyping data available for CF Pa in France. Forty-four CF patients with a first Pa colonization were included; 265 strains collected over 7 years in these patients were genotyped by multiplex rep-PCR, multilocus sequence typing, pulsed-field gel electrophoresis and/or whole genome sequencing. Forty-one sequence types were identified: 4 were unknown, 22 never previously reported for CF patients, and 6 corresponded to widespread clones colonizing 16 patients (36%). Unrelated strains were identified in 41 patients (93%). Twenty-six patients (59%) presented a recurrence during the study period. No specific clones were associated with transient, recurrent or persistent colonization. Our longitudinal study revealed that 9 of the 26 patients with recurrence (35%) harbored strains of different genotypes. Great genetic diversity was observed among initial Pa isolates excluding any cross-transmission. Recurrence and persistent colonization were not associated with any specific clone. Persistent colonization appeared more complex than expected, imitating persistence, with successive colonization events by unrelated Pa.

PMID:37832753 | DOI:10.1016/j.meegid.2023.105513