Ligand-free biodegradable poly(beta-amino ester) nanoparticles for targeted systemic delivery of mRNA to the lungs.

Non-viral nanoparticles (NPs) have seen heightened interest as a delivery method for a variety of clinically relevant nucleic acid cargoes in recent years. While much of the focus has been on lipid NPs, non-lipid NPs, including polymeric NPs, have the possibility of improved efficacy, safety, and targeting, especially to non-liver organs following systemic administration. A safe and effective systemic approach for intracellular delivery to the lungs could overcome limitations to intratracheal/intranasal delivery of NPs and improve clinical benefit for a range of diseases including cystic fibrosis. Here, engineered biodegradable poly (beta-amino ester) (PBAE) NPs are shown to facilitate efficient delivery of mRNA to primary human airway epithelial cells from both healthy donors and individuals with cystic fibrosis. Optimized NP formulations made with differentially endcapped PBAEs and systemically administered in vivo lead to high expression of mRNA within the lungs in BALB/c and C57 B/L mice without requiring a complex targeting ligand. High levels of mRNA-based gene editing were achieved in an Ai9 mouse model across bronchial, epithelial, and endothelial cell populations. No toxicity was observed either acutely or over time, including after multiple systemic administrations of the NPs. The non-lipid biodegradable PBAE NPs demonstrate high levels of transfection in both primary human airway epithelial cells and in vivo editing of lung cell types that are targets for numerous life-limiting diseases particularly single gene disorders such as cystic fibrosis and surfactant deficiencies.

The battle within: how Pseudomonas aeruginosa uses host-pathogen interactions to infect the human lung.

Pseudomonas aeruginosa is a versatile Gram-negative pathogen known for its ability to invade the respiratory tract, particularly in cystic fibrosis patients. This review provides a comprehensive analysis of the multifaceted strategies for colonization, virulence, and immune evasion used by P. aeruginosa to infect the host. We explore the extensive protein arsenal of P. aeruginosa, including adhesins, exotoxins, secreted proteases, and type III and VI secretion effectors, detailing their roles in the infective process. We also address the unique challenge of treating diverse lung conditions that provide a natural niche for P. aeruginosa on the airway surface, with a particular focus in cystic fibrosis. The review also discusses the current limitations in treatment options due to antibiotic resistance and highlights promising future approaches that target host-pathogen protein-protein interactions. These approaches include the development of new antimicrobials, anti-attachment therapies, and quorum-sensing inhibition molecules. In summary, this review aims to provide a holistic understanding of the pathogenesis of P. aeruginosa in the respiratory system, offering insights into the underlying molecular mechanisms and potential therapeutic interventions.

Collaboration between registered dietitians and gastroenterologists in cystic fibrosis care: Results of an international cross-sectional survey.

BACKGROUND: Collaboration between registered dietitians and gastroenterologists has not been evaluated in cystic fibrosis (CF). We surveyed registered dietitians and gastroenterologists regarding the current participation of gastroenterologists in CF centers and identified possible areas to enhance partnership between the two disciplines. METHODS: An anonymous online survey was distributed targeting registered dietitians and gastroenterologists involved in CF care through three international listservs (CF Nutrition, CF DIGEST, and PEDGI) over a 6-week period. SurveyMonkey was used, and informed consent was obtained. RESULTS: A total of 131 respondents participated in this survey, including 80 registered dietitians and 51 gastroenterologists (41 pediatric and 10 adult gastroenterologists). Most respondents (82%) were from the United States, and two-thirds had ≥5 years of experience in CF. A significant number of registered dietitians reported the nonavailability of gastroenterologists for collaboration and there was greater availability of gastroenterologists in pediatric centers. Barriers to interdisciplinary collaboration included lack of CF expertise and dedicated time among the gastroenterologists and difficulties in coordinating the gastroenterology clinics. More gastroenterologists than registered dietitians perceived that they worked collaboratively with the other discipline in various domains (clinical care, quality improvement, research, presentations, and publications). Both disciplines had mutual respect and interest to further the collaboration. CONCLUSION: There is an increased need for gastroenterologist participation and collaboration (particularly in adult centers) in CF alongside registered dietitians to enhance comprehensive patient care. Future efforts should focus on training more gastroenterologists in CF and facilitating easier access to gastroenterologists for the CF population.

Effect of Lactiplantibacillus plantarum cell-free culture on bacterial pathogens isolated from cystic fibrosis patients: in vitro and in vivo studies.

This study aimed to investigate the effects of the cell-free supernatant of Lactiplantibacillus plantarum ATCC® 10241TM on the biofilm-forming capacity of Pseudomonas aeruginosa strains isolated from cystic fibrosis (CF) patients. In addition, the study evaluated the in vivo potential of the cell-free supernatant to modulate inflammation and reduce lung damage in mice infected with P. aeruginosa strains or co-challenged with P. aeruginosa and the Streptococcus milleri group (SMG). The results showed that CF-derived P. aeruginosa strains can infect the respiratory tract of adult mice, inducing local inflammation and lung damage. The severity of these infections was exacerbated when P. aeruginosa was co-administered with SMG. Notably, nebulization with the cell-free supernatant of L. plantarum produced beneficial effects, reducing respiratory infection severity and inflammatory responses induced by P. aeruginosa, both alone or in combination with SMG. Reduced bacterial loads and lung damage were observed in supernatant-treated mice compared to controls. Although further mechanistic studies are necessary, the results show that the cell-free supernatant of L. plantarum ATCC® 10241TM is an interesting adjuvant alternative to treat P. aeruginosa respiratory infections and superinfections in CF patients.

CCR2+ monocytes are dispensable to resolve acute pulmonary Pseudomonas aeruginosa infections in WT and Cystic Fibrosis mice.

Extravasation of CCR2-positive monocytes into tissue and to the site of injury is a fundamental immunological response to infections. Nevertheless, exuberant recruitment and/or activity of these monocytes and monocyte-derived macrophages can propagate tissue damage, especially in chronic inflammatory disease conditions. We have previously shown that inhibiting the recruitment of CCR2-positive monocytes ameliorates lung tissue damage caused by chronic neutrophilic inflammation in cystic fibrosis (CF) mouse models. A potential concern with targeting monocyte recruitment for therapeutic benefit in CF, however, is whether they are essential for eradicating infections such as Pseudomonas aeruginosa (PA), a pathogen that commonly colonizes and damages the lungs of patients with CF. In this study, we investigated the role of CCR2-positive monocytes in the immune response to acute pulmonary PA infection. Our data show that the altered host immune response caused by the lack of monocyte recruitment to the lungs does not impact PA lung colonization, clearance, and the severity of the infection. These results also hold up in a CF mouse background, which have a hyper-inflammatory immune response, yet exhibit reduced bactericidal activity. Thus, we lay the groundwork for future studies to investigate the use of CCR2 inhibitors as a potential therapy to ameliorate lung tissue damage in CF. This could be given alone or as an adjunct therapy with CFTR modulators that significantly improve clinical outcomes for eligible patients, but do not completely resolve the persistent infection and inflammation that drive lung tissue damage.

Challenges in the care of cystic fibrosis in low-to-middle income countries.

Till few years ago cystic fibrosis (CF) was considered to be exclusively disease affecting Caucasian population. More recently CF has been reported from all over the world from different ethnic background. CF is an emerging illness in other parts of world (India with 1:2200 to 1:40,000 live birth). In low- and middle-income countries (LMICs) diagnosis of CF is missed due to ignorance and nonavailability of diagnostic tests. Diagnosis can be made using clinical features and basic lab tests. As of now there is no cure, but supportive care improved survival. However, medicines used in higher income countries are very expensive and not accessible to children with CF in LMICs. Cystic fibrosis transmembrane regulators modulators have emerged as significant advances in management. These are very expensive and beyond the reach of patients in LMICs. CF Fraternity in developed countries should work towards training of personnel and possibly making medications available in LMICs.

Integrating genomics as clinical biomarkers in pediatric pulmonology.

Respiratory diseases often result from complex interactions between an individual's genetic predisposition and their exposure to various environmental and other risk factors. Here we will briefly review how various types of "omics", particularly epigenomics and transcriptomics, hold promise for translation into clinical biomarkers in pediatric pulmonary medicine, using asthma and cystic fibrosis as examples.

Kidney effects of triple CFTR modulator therapy in people with cystic fibrosis.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) is a new cystic fibrosis transmembrane conductance regulator (CFTR) modulator that has transformed the respiratory prognosis of people with cystic fibrosis (pwCF). However, its impact on other organs such as the kidneys, where CFTR is expressed, remains unclear. Since pwCF are risk of both kidney disease and urolithiasis, we aimed to study the potential effects of ETI on renal function, volume status, and risk factors for urolithiasis. Methods: This prospective, observational, single-center, before-after cohort study, involved adult pwCF eligible for ETI. The changes in plasma and urinary profiles were assessed by comparing renal function (using 2021 CKD-EPIcreatinine and 2021 CKD-EPIcreatinine-cystatin C formulas), volume status (using aldosterone/renin ratio and blood pressure), and risk factors for urolithiasis, at the time of ETI introduction (M0) and 7 months after (M7). Results: Nineteen pwCF were included. No significant change in renal function was observed between M0 and M7 (2021 CKD-EPIcreatinine: 105.5 ml/min/1.73 m² at M0 vs. 103.3 ml/min/1.73 m² at M7; P = .17). There was a significant reduction in aldosterone level (370.3 pmol/l at M0 vs. 232.4 pmol/l at M7; P = .02) and aldosterone/renin ratio (33.6 at M0 vs. 21.8 at M7; P = .03). Among the risk factors for urolithiasis, a significant reduction in magnesuria level was found (4.6 mmol/d at M0 vs. 3.8 mmol/d at M7; P = .01). Conclusion: These findings suggest that ETI seem to have no short-term impact on the renal function of adult pwCF and appears to correct secondary hyperaldosteronism due to excessive sweat losses. Further investigations are needed to determine the potential impact of decreased magnesuria observed under ETI therapy on the risk of urolithiasis.

Effectiveness of hypertonic saline with or without hyaluronic acid among patients with cystic fibrosis: a systematic review and meta-analysis.

Background: The clinical effectiveness of hypertonic saline (HS) in individuals with cystic fibrosis (CF) can be compromised by adverse effects. The objective of this study was to examine the efficacy of hyaluronic acid (HA) in mitigating these negative occurrences. Methods: A comprehensive review of the literature was carried out using three electronic databases: Medline, Cochrane Central, and Embase. This systematic review and meta-analysis investigate the efficacy of hypertonic saline (HS) with and without hyaluronic acid (HA) in treating cystic fibrosis. Primary outcomes include the incidence of cough, throat irritation, unpleasant taste, and changes in FEV1. Our findings suggest that adding HA to HS significantly reduces adverse effects and enhances patient tolerability, marking a potential improvement in cystic fibrosis therapy. Risk ratios (RRs) and mean differences (MDs) with 95% CI were used to present evaluations. The quality of RCTs was evaluated using the Cochrane Risk of Bias Tool (CRBT). The quality of the observational study was evaluated using the Newcastle-Ottawa Scale. Results: From the 1960 articles retrieved from the initial search, five relevant studies (n=236 patients) were included in the final analysis. Compared with patients only on HS, patients with HS and HA were significantly less likely to experience cough (RR: 0.45; 95% CI, 0.28-0.72, P=0.001), throat irritation (RR: 0.43; 95% CI, 0.22-0.81, P=0.009), and unpleasant smell (RR: 0.43; 95% CI, 0.23-0.80, P=0.09). In addition, patients with HS with HA had significantly less forced expiratory volume (FEV1) (MD: -2.97; 95% CI, -3.79--2.15, P=0.52), compared to patients only on HS. Patients on HA + HS had significantly lower rates of cough (RR: 0.45; 95% CI, 0.28-0.72, P=0.001), throat irritation (RR: 0.43; 95% CI, 0.22-0.81, P=0.009), and bad smell (RR: 0.43; 95% CI, 0.23-0.80, P=0.09) when compared to patients on HS alone. Furthermore, compared to patients solely on HS, patients with HS plus HA exhibited a substantially lower forced expiratory volume (FEV1) (MD: -2.97; 95% CI, -3.79 to -2.15, P=0.52) as well. Conclusion: For CF patients who need ongoing HS therapy and have a history of poor therapy tolerance, adding HA is beneficial.

A comparative study of the efficacy of alginate lyases in the presence of metal ions elevated in the cystic fibrosis lung milieu.

Pseudomonas aeruginosa, a common cause of morbidity in cystic fibrosis, chronically infects the patient's lungs by forming an alginate-containing biofilm. Alginate lyases are polysaccharide lyases that lyse alginate and are, therefore, potential biofilm-disruptive agents. However, cystic fibrosis sputum contains high levels of metals such as iron and zinc. The efficacy of alginate lyases under these conditions of elevated metal concentrations has not been categorically determined. Here, we have assessed the enzyme activity of two exolytic and five endolytic alginate lyases in the presence of metal ions (Fe2+, Zn2+, Mn2+, Mg2+, Ca2+, Ni2+, Cu2+) elevated in the cystic fibrosis lung milieu. Several of these alginate lyases exhibited increased activity in the presence of Ca2+, and the polysaccharide lyase family 7 members studied here exhibited decreased activity in the presence of Zn2+. The enzyme activity of the PL7 alginate lyases from Cellulophaga algicola (CaAly/CaFLDAly) and Vibrio sp. (VspAlyVI) was not affected in the presence of a mix of all the above-mentioned metal ions at the elevated concentrations found in the cystic fibrosis lung milieu. Specific alginate lyases might, therefore, retain the ability to degrade the alginate-containing Pseudomonas biofilm in the presence of metal ions elevated in the cystic fibrosis lung milieu.

The Omega-6 Lipid pathway shift is associated with neutrophil influx and structural lung damage in early cystic fibrosis lung disease.

Objectives: In cystic fibrosis (CF), an imbalanced lipid metabolism is associated with lung inflammation. Little is known about the role that specific lipid mediators (LMs) exert in CF lung inflammation, and whether their levels change during early disease progression. Therefore, we measured airway LM profiles of young CF patients, correlating these with disease-associated parameters. Methods: Levels of omega (ω)-3/6 PUFAs and their LM derivatives were determined in bronchoalveolar lavage fluid (BALF) of children with CF ages 1-5 using a targeted high-performance liquid chromatography-tandem mass spectrometry approach. Hierarchical clustering analysis was performed on relative LM levels. Individual relative LM levels were correlated with neutrophilic inflammation (BALF %Neu) and structural lung damage (PRAGMA-CF %Disease). Significant correlations were included in a backward multivariate linear regression model to identify the LMs that are best related to disease progression. Results: A total of 65 BALF samples were analysed for ω-3/6 lipid content. LM profiles clustered into an arachidonic acid (AA)-enriched and a linoleic acid (LA)-enriched sample cluster. AA derivatives like 17-OH-DH-HETE, 5-HETE, 5,15-diHETE, 15-HETE, 15-KETE, LTB4 and 6-trans-LTB4 positively correlated with BALF %Neu and/or PRAGMA %Dis. Contrastingly, 9-HoTrE and the LA derivatives 9-HoDE, 9(10)-EpOME, 9(10)-DiHOME, 13-HoDE, 13-oxoODE and 12(13)-EpOME negatively correlated with BALF %Neu and/or PRAGMA %Dis. 6-trans-LTB4 was the strongest predictor for BALF %Neu. 5-HETE and 15-KETE contributed most to PRAGMA %Dis prediction. Conclusions: Our data provide more insight into the lung lipidome of infants with CF, and show that a shift from LA derivatives to AA derivatives in BALF associates with early CF lung disease progression.

Biochemical assessment in a cohort of pediatric patients with cystic fibrosis.

Cystic fibrosis (CF) is a recessive inherited disorder caused by genetic mutations in the CF transmembrane conductance regulator (CFTR) gene. It is a multisystem condition that primarily induces abnormal mucus accumulation in the respiratory system and obstructs the intrapancreatic common bile duct, causing a reduction in the delivery of digestive enzymes to the small intestine. Thus, patients with CF are characterized by maldigestion, malabsorption, and recurrent airway bacterial infections. Clinical monitoring of the health status of patients with CF is mandatory for increasing the patients' lifespan. To assess the feasibility of monitoring life quality (LQ) in pediatric patients with cystic fibrosis (CF) and to explore the relationship between biochemical parameters and clinical symptoms, our study analyzed inflammatory responses related to CF, medication, and pulmonary bacterial infections in 52 patients diagnosed with CF. Blood, hypo-pharyngeal exudate, and fecal samples were analyzed using clinical biochemistry, hematology, and microbiology techniques at the Alessandrescu-Rusescu National Institute for Mother and Child Health central laboratory in Bucharest, Romania. All the participants adhered to their prescribed outpatient CF regimens and appeared clinically stable. The overall clinical status of patients with CF was observed and compared with that of a healthy control group, which consisted of individuals similar in number and age. The screened patients with CF presented an impaired lipid status and chronic infections with various bacteria, iron, and vitamin (A, D, and E) deficiencies. Our findings provide insights into the pathophysiological mechanisms of CF and suggest that tailored monitoring and personalized therapeutic strategies could improve patient management.

Clinical Course of a Child With Cystic Fibrosis and the Genotype F508del/CFTRdup1_11: A Case Report.

Cystic fibrosis (CF) is a hereditary disease with great genetic complexity as not all mutations are disease-causing and genotype doesn't always predict phenotype. This case involves a child with CF and genotype F508del/CFTRdup1_11. The CFTRdup1_11 duplication was not reported previously, and genetic counseling was based on reports describing the clinical course of people carrying smaller duplications of the same area combined with F508del. The predicted clinical presentation was CF with pancreatic insufficiency. However, the case presented has so far shown no clinical symptoms and has borderline sweat chloride concentrations.

Outcomes of single vs double lung retransplantation in patients with cystic fibrosis.

BACKGROUND: Patients requiring lung transplant for cystic fibrosis (CF) may require retransplant due to limited graft survival and otherwise excellent life expectancy. Optimal transplant strategy for this population, including single vs double lung retransplant, has not been established. METHODS: We performed a retrospective analysis of the United Network for Organ Sharing/Organ Procurement and Transplant Network (UNOS/OPTN) database to identify adult lung retransplant recipients from 2005 to 2021 with a primary diagnosis of CF. Patients were stratified by retransplant type (single lung [re-SLTx] vs double lung [re-DLTx] retransplant). Descriptive statistics, Kaplan-Meier survival analysis, and multivariable Cox regression were performed. RESULTS: From 2005 to 2021, 384 recipients underwent retransplant after an initial transplant for an indication of CF; more recipients underwent re-DLTx (N = 337 [87.8%]) than re-SLTx (N = 47 [12.2%]). The median (IQR) time from initial transplant to retransplant was similar between re-SLTx and re-DLTx recipients (4.4 [2.9-8.6] vs 4.6 [2.6-7.4] years, p = 0.73). Ischemic time was shorter and lung allocation score was lower for re-SLTx than re-DLTx recipients. Median survival after retransplant was significantly shorter for re-SLTx vs re-DLTx recipients (2.0 [95% CI 1.2-3.5] vs 4.3 [95% CI 3.5-6.1] years post-retransplant, p = 0.008). Median survival for adults with CF undergoing primary transplant for CF in the same period was 9.1 (8.5-9.9) years. After adjusting for donor and recipient characteristics, re-SLTx in patients with CF was associated with 88% higher hazard of mortality than re-DLTx (aHR=1.88 [95% CI 1.28-2.78], p = 0.001). CONCLUSIONS: In this analysis of lung retransplant in recipients with CF, re-SLTx was associated with a higher hazard of mortality compared to re-DLTx, supporting re-DLTx as treatment for this population.

IL-6 and TIMP-1 Correlated to Airway Pathogen Colonization and Predict Disease Severity in Patients with Non-Cystic Fibrosis Bronchiectasis.

Background: Non-cystic fibrosis bronchiectasis is associated with airway pathogen colonization. We planned to investigate the inflammatory markers in patients with different airway pathogens and their correlation with disease severity. Methods: We enrolled patients aged between 20 and 75 from October 2021 to August 2022. All patients had sputum evaluation for bacterial and fungal cultures before enrollment, and were classified into four groups according to the culture results. Results: Forty-four patients with non-CF bronchiectasis and six controls were enrolled and categorized as follows: Group 1, no pathogens identified in sputum cultures (n = 14); Group 2, positive fungal culture results (n = 18); Group 3, positive P. aeruginosa culture results (n = 7); and Group 4, positive culture results for both fungi and P. aeruginosa (n = 5). Group 4 had significantly higher serum defensin α1, IL-6 and tissue inhibitors of MMP (TIMP)-1 levels than group 1 patients. The serum levels of IL-6 and TIMP-1 were positively correlated with the FACED score and negatively correlated with distance-saturation product. Conclusion: Significantly higher levels of serum IL-6 and TIMP-1 were found in the patients who had concomitant fungal and P. aeruginosa colonization, and were closely related to clinical severity and may have important roles in disease monitoring.

Incidence of bronchiectasis in patients with acromegaly: a cohort study.

Objective: Associations between acromegaly and several respiratory diseases, such as obstructive lung disease or sleep apnea, have been suggested, but the relationship between bronchiectasis and acromegaly is unclear. We investigated whether acromegaly is related to the development of bronchiectasis. Materials and methods: Using the Korean National Health Insurance System database between 2006 and 2016, we studied the relationship between acromegaly and bronchiectasis in patients with acromegaly (n=2593) and controls (1:5 age- and sex-matched subjects without acromegaly, n=12965) with a mean follow-up period of 8.9 years. Cox proportional hazards regression analysis was used to assess the risk of bronchiectasis in patients with acromegaly compared with controls after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia. Results: The mean age of the participants was 47.65 years, and male subjects comprised 45.62% of the cohort. The incidence rate of bronchiectasis in patients with acromegaly was 3.64 per 1,000 person-years and was significantly higher than that in controls (2.47 per 1,000 person-years) (log-rank test p = 0.002). In multivariable Cox proportional hazards regression modeling, the risk of bronchiectasis was significantly higher in patients with acromegaly than that in controls (HR: 1.49; 95% CI: 1.15-1.94, p = 0.0025) after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia. Conclusions: Our results suggest that acromegaly may be associated with bronchiectasis.

Evaluating precision medicine tools in cystic fibrosis for racial and ethnic fairness.

Introduction: Patients with cystic fibrosis (CF) experience frequent episodes of acute decline in lung function called pulmonary exacerbations (PEx). An existing clinical and place-based precision medicine algorithm that accurately predicts PEx could include racial and ethnic biases in clinical and geospatial training data, leading to unintentional exacerbation of health inequities. Methods: We estimated receiver operating characteristic curves based on predictions from a nonstationary Gaussian stochastic process model for PEx within 3, 6, and 12 months among 26,392 individuals aged 6 years and above (2003-2017) from the US CF Foundation Patient Registry. We screened predictors to identify reasons for discriminatory model performance. Results: The precision medicine algorithm performed worse predicting a PEx among Black patients when compared with White patients or to patients of another race for all three prediction horizons. There was little to no difference in prediction accuracies among Hispanic and non-Hispanic patients for the same prediction horizons. Differences in F508del, smoking households, secondhand smoke exposure, primary and secondary road densities, distance and drive time to the CF center, and average number of clinical evaluations were key factors associated with race. Conclusions: Racial differences in prediction accuracies from our PEx precision medicine algorithm exist. Misclassification of future PEx was attributable to several underlying factors that correspond to race: CF mutation, location where the patient lives, and clinical awareness. Associations of our proxies with race for CF-related health outcomes can lead to systemic racism in data collection and in prediction accuracies from precision medicine algorithms constructed from it.

Exploring the complexity of cystic fibrosis (CF) and psychosocial wellbeing in the 2020s: Current and future challenges.

Cystic fibrosis (CF) is traditionally associated with considerable and progressive multisystem pathology, onerous treatment burden, complex psychosocial challenges, and reduced life-expectancy [1-9].This decade has seen transformative change in management for many, but not all, people with CF. The most notable change comes from Cystic Fibrosis Transmembrane Receptor (CFTR) modulators, which bring significant benefits for people who are eligible for, and able to access, them [10]. However alongside, or perhaps because of, this exciting progress, the past few years have also brought important novel challenges to the psychosocial wellbeing of people with CF. This article, written as a collaboration between CF psychologists, social workers, physicians and nurses aims to provide an accessible overview of the novel psychosocial challenges now faced by children, their families, and adults with CF, and to invite consideration of their changing psychosocial requirements to inform future holistic care. Themes include geopolitical stressors such as the pandemic and its wake, a growing divide between those able or unable to access CFTR modulators, potential rapid changes in life expectancy secondary to these drugs and the inevitable associated challenges this brings; evolving body image, mental health side effects of CFTR modulators, the challenges of adherence in apparently well children and young adults, as well as the diagnostic conundrum and associated anxiety of the cystic fibrosis screen positive inconclusive diagnosis (CFSPID) label. It also highlights some unmet research and service delivery needs in the area.

[Sodium depletion assessed by the urinary sodium/creatinine ratio in monitoring cystic fibrosis patients]. / Déplétion sodée évaluée par le ratio sodium/créatinine urinaire dans le suivi des patients atteints de mucoviscidose.

As a result of excessive salt loss, cystic fibrosis patients are at risk of dehydration, especially in hot weather. The urinary sodium/creatinine ratio is an easy and noninvasive tool for assessing whether dietary salt intake is adequate, whatever the patient's age. Recently, new reference values have been established, adapted to the patient's age. The objectives of this study are to investigate the impact of these new standards on the diagnosis of inadequate sodium intake and the variation in this ratio as a function of body mass index (BMI), outdoor temperature and the use of modulator therapy of CFTR protein. The present study included 40 patients and 335 urine samples. Adapting the urinary sodium/creatinine ratio with the new reference values reduced the number of patients with sodium deficiency by 11.8%. However, there were no significant differences in BMI, lung function or outdoor temperature between the sodium deficient and non-deficient groups. The CFTR modulator-treated group had a better mean urinary sodium/creatinine ratio compared with the group without modulators (p = 0.01), However, larger-scale studies are needed to provide a definitive answer to this question.

Suite à des pertes excessives en sel, les patients atteints de mucoviscidose sont à risque de déshydratation, surtout lors de fortes chaleurs. Le ratio sodium/créatinine urinaire est un outil simple et non invasif permettant d'évaluer l'adéquation des apports en sel dans l'alimentation du patient quel que soit son âge. Récemment, de nouvelles valeurs de référence ont été établies en fonction de l'âge. Les objectifs de cette étude sont d'étudier la répercussion de ces nouvelles normes sur le constat d'un apport sodé insuffisant pour le patient ainsi que la variation de ce ratio en fonction de l'indice de masse corporelle (IMC), de la température extérieure et de la prise d'un modulateur de la protéine CFTR. Cette étude comporte 40 patients et un total de 335 prélèvements urinaires. L'adaptation du ratio sodium/créatinine urinaire permet de réduire de 11,8 % le nombre de patients en déficit sodé. Il n'y a, par contre, pas de différences significatives concernant l'IMC, la fonction respiratoire et les températures extérieures, entre les groupes avec ou sans déficit sodé. Le groupe traité par un modulateur de la protéine CFTR a un meilleur ratio sodium/créatinine urinaire moyen en comparaison au groupe sans ce traitement (p = 0,01). Cependant, des études à plus large échelle sont nécessaires pour répondre de façon formelle à la question.