Diabetologia. 2024 Jul 12. doi: 10.1007/s00125-024-06223-3. Online ahead of print.

ABSTRACT

People with cystic fibrosis (CF) are at risk for dysglycaemia caused by progressive beta cell dysfunction and destruction due to pancreatic exocrine disease and fibrosis. CF-related diabetes (CFRD) is a unique form of diabetes that has distinctive features from both type 1 and type 2 diabetes. Recent advances in diabetes technology may be of particular benefit in this population given the complex, multi-system organ involvement and challenging health issues that people with CFRD often face. This review summarises how diabetes technologies, such as continuous glucose monitors (CGMs) and insulin delivery devices: (1) have improved our understanding of CFRD, including how hyperglycaemia affects clinical outcomes in people with CF; (2) may be helpful in the screening and diagnosis of CFRD; and (3) offer promise for improving the management of CFRD and easing the burden that this diagnosis can add to an already medically complicated patient population.

PMID:38995399 | DOI:10.1007/s00125-024-06223-3

Pediatr Pulmonol. 2024 Jul 12. doi: 10.1002/ppul.27176. Online ahead of print.

ABSTRACT

BACKGROUND: The benefit of antibiotic treatment of acute drops in FEV1 percent predicted (FEV1pp) has been clearly established, but data from the early 2000s showed inconsistent treatment. Further, there is no empirical evidence for what magnitude of drop is clinically significant.

METHODS: We used data from the CF Foundation Patient Registry (CFFPR) from 2016 to 2019 to determine the association between treatment (any IV antibiotics, only oral or newly prescribed inhaled antibiotics, or no antibiotic therapy) following a decline of ≥5% from baseline FEV1pp and return to 100% baseline FEV1pp days using multivariable logistic regression including an interaction between the magnitude of decline and treatment category.

RESULTS: Overall, 16,495 PWCF had a decline: 16.5% were treated with IV antibiotics, 25.0% non-IV antibiotics, and 58.5% received no antibiotics. Antibiotic treatment was more likely for those with lower lung function, history of a positive PA culture, older age and larger FEV1 decline (p < 0.001). Treatment with IV antibiotics or oral/inhaled antibiotics was associated with a higher odds of recovery to baseline compared to no treatment across all levels of decline, including declines of 5%-10%.

CONCLUSIONS: A large proportion of acute drops in FEV1pp continue to be untreated, especially in younger patients and those with higher baseline lung function. Acute drops as small as 5% predicted are less likely to be recovered if antibiotic treatment is not prescribed. These findings suggest the need for more aggressive antimicrobial treatment of acute drops in FEV1, including those of a magnitude previously believed to be associated with self-recovery.

PMID:38995116 | DOI:10.1002/ppul.27176

J Clin Endocrinol Metab. 2024 Jul 12:dgae474. doi: 10.1210/clinem/dgae474. Online ahead of print.

ABSTRACT

CONTEXT: The pathophysiological mechanisms underlying the natural history of glucose intolerance and its fluctuations in subjects with cystic fibrosis (CF) are still unclear.

OBJECTIVE: To investigate the relationship between longitudinal changes in glucose tolerance and concomitant changes in the main parameters of insulin secretion/metabolism/action determining glucose regulation in CF subjects.

METHODS: Insulin sensitivity and glucose-stimulated insulin secretion (GSIS, a biomarker of beta cell functional mass), as estimated by the Oral Glucose Sensitivity Index (OGIS) and by a sophisticated mathematical model, respectively, and insulin clearance were assessed in 127 CF subjects, aged 10-25 years, who underwent two OGTT tests over at least 1-year follow-up period. Subjects were classified a posteriori as regressors (improved glucose tolerance), stable, or progressors (worsened glucose tolerance). The interplay between beta cell compensatory action and insulin sensitivity over time was analyzed by vector plots of insulin clearance adjusted GSIS (PCadj) versus OGIS.

RESULTS: OGIS decreased in progressors and stable. Insulin clearance decreased in both regressors and progressors. GSIS (beta cell functional mass) improved in regressors and worsened in progressors, whereas it did not change in stable. Vector plot analysis confirmed that glucose regulation changed differently in each group. Multinomial logistic regression analysis showed that baseline glucose tolerance and GSIS changes were the only significant predictors of the changes in glucose tolerance (p<0.02, R2Nagelkerke=0.55), whereas age, gender, z-BMI, CF genotypes, and baseline PCadj were not.

CONCLUSIONS: In CF subjects, changes in beta cell functional mass are associated with favorable or detrimental changes of glucose tolerance over time.

PMID:38994570 | DOI:10.1210/clinem/dgae474

Front Transplant. 2022 Sep 23;1:992985. doi: 10.3389/frtra.2022.992985. eCollection 2022.

ABSTRACT

Cystic fibrosis (CF) is a multisystem disorder and represents the most common inherited condition leading to death in Western countries. Previous reports of chronic kidney disease (CKD) in CF focus on cases post lung, or other solid organ, transplantation but CKD in CF patients pre transplantation is increasingly recognized as a challenging complication of CF. CKD can evolve as a sequel to acute kidney injury for example after prolonged treatment with aminoglycoside antibiotics during episodes of infection. Nephrolithiasis, diabetic nephropathy and a variety of glomerular lesions, such as amyloidosis and Immunoglobulin A nephropathy are also seen. Muscle depletion is common in CF, hence creatinine-based estimates of kidney function may underestimate the degree of renal impairment and lead to delayed diagnosis and management. Improved treatment options for CF patients have resulted in a sustained increase in life expectancy with increasing numbers of CF patients with CKD approaching end-stage renal failure prior to consideration of lung transplantation. We believe that kidney or combined kidney-pancreas transplantation are under-utilized in this population. We provide a brief primer on the landscape of CF and CKD and discuss transplant options. Suitable patients with CF and advanced CKD should be formally assessed for kidney or kidney-pancreas transplantation.

PMID:38994374 | PMC:PMC11235247 | DOI:10.3389/frtra.2022.992985

SSM Qual Res Health. 2024 Jun;5:100412. doi: 10.1016/j.ssmqr.2024.100412. Epub 2024 Feb 24.

ABSTRACT

This article offers the case of cystic fibrosis (CF), a multi-system disease, to illustrate how individuals with chronic illness cultivate and apply embodied knowledge to optimize their well-being. We identified three interrelated processes that occur when disease chronicity and menstrual cyclicity meet: 1) knowledge production with a period-tracking app; 2) application of embodied knowledge to manage life with menstrual-related CF symptoms; 3) cultivation of the body-self as a menstruating woman with CF. These dynamic processes capture how cis-gender women with CF attune to their bodies, navigate their illness, and situate themselves within their lifeworlds. Genetic conditions like CF are apt for studying these processes because adults have managed their disease for decades, with longitudinal experience that often exceeds that of their clinicians. Our evidence elucidates the co-constitutive nature of chronic disease, gendered subjectivity, and biological processes in flux. We explored the menstrual cyclicity of chronic disease symptoms by having 72 participants track their CF symptoms across 4 menstrual cycles on a customized period-tracking app. We performed semi-structured interviews with 20 participants to understand how they interpreted these cyclical CF symptoms. We learned that digital tracking attuned participants to monthly fluctuations in CF symptoms. They applied this knowledge to manage their lives and shape their sense of self. We argue that women with CF produce distinct embodied knowledge during their reproductive years, shaping their illness experience, disease management, overall health, quality of life, and selfhood. The dynamics we describe may reflect broader patterns by which women with other chronic illnesses experience their bodies and understand themselves in the world.

PMID:38993933 | PMC:PMC11238905 | DOI:10.1016/j.ssmqr.2024.100412

J Am Acad Dermatol. 2024 Jul 9:S0190-9622(24)01038-7. doi: 10.1016/j.jaad.2024.06.075. Online ahead of print.

NO ABSTRACT

PMID:38992504 | DOI:10.1016/j.jaad.2024.06.075

J Am Acad Dermatol. 2024 Jul 9:S0190-9622(24)01039-9. doi: 10.1016/j.jaad.2024.07.008. Online ahead of print.

NO ABSTRACT

PMID:38992503 | DOI:10.1016/j.jaad.2024.07.008

Lancet. 2024 Jul 8:S0140-6736(24)00909-7. doi: 10.1016/S0140-6736(24)00909-7. Online ahead of print.

ABSTRACT

BACKGROUND: International guidelines have recommended cognitive behavioural therapy, including acceptance and commitment therapy (ACT), as it offers validated benefits for managing fibromyalgia; however, it is inaccessible to most patients. We aimed to evaluate the effect of a 12-week, self-guided, smartphone-delivered digital ACT programme on fibromyalgia management.

METHODS: In the PROSPER-FM randomised clinical trial conducted at 25 US community sites, adult participants aged 22-75 years with fibromyalgia were recruited and randomly assigned (1:1) to the digital ACT group or an active control group that offered daily symptom tracking and monitoring and access to health-related and fibromyalgia-related educational materials. Randomisation was done with a web-based system in permuted blocks of four at the site level. We used a blind-to-hypothesis approach in which participants were informed they would be randomly assigned to one of two potentially effective therapies under evaluation. Research staff were not masked to group allocation, with the exception of a masked statistics group while preparing statistical programming for the interim analysis. The primary endpoint was patient global impression of change (PGIC) response rate at week 12. Analyses were by intention to treat. The trial was registered with ClinicalTrials.gov, NCT05243511 (now fully closed).

FINDINGS: Between Feb 8, 2022, and Feb 2, 2023, 590 individuals were screened, of whom 275 (257 women and 18 men) were randomly assigned to the digital ACT group (n=140) and the active control group (n=135). At 12 weeks, 99 (71%) of 140 ACT participants reported improvement on PGIC versus 30 (22%) of 135 active control participants, corresponding to a difference in proportions of 48·4% (95% CI 37·9-58·9; p<0·0001). No device-related safety events were reported.

INTERPRETATION: Digital ACT was safe and efficacious compared with digital symptom tracking in managing fibromyalgia in adult patients.

FUNDING: Swing Therapeutics.

PMID:38991582 | DOI:10.1016/S0140-6736(24)00909-7

PLoS Pathog. 2024 Jul 11;20(7):e1012394. doi: 10.1371/journal.ppat.1012394. Online ahead of print.

ABSTRACT

Staphylococcus aureus is a facultative intracellular pathogen of human macrophages, which facilitates chronic infection. The genotypes, pathways, and mutations influencing that phenotype remain incompletely explored. Here, we used two distinct strategies to ascertain S. aureus gene mutations affecting pathogenesis in macrophages. First, we analyzed isolates collected serially from chronic cystic fibrosis (CF) respiratory infections. We found that S. aureus strains evolved greater macrophage invasion capacity during chronic human infection. Bacterial genome-wide association studies (GWAS) identified 127 candidate genes for which mutation was significantly associated with macrophage pathogenesis in vivo. In parallel, we passaged laboratory S. aureus strains in vitro to select for increased infection of human THP-1 derived macrophages, which identified 15 candidate genes by whole-genome sequencing. Functional validation of candidate genes using isogenic transposon mutant knockouts and CRISPR interference (CRISPRi) knockdowns confirmed virulence contributions from 37 of 39 tested genes (95%) implicated by in vivo studies and 7 of 10 genes (70%) ascertained from in vitro selection, with one gene in common to the two strategies. Validated genes included 17 known virulence factors (39%) and 27 newly identified by our study (61%), some encoding functions not previously associated with macrophage pathogenesis. Most genes (80%) positively impacted macrophage invasion when disrupted, consistent with the phenotype readily arising from loss-of-function mutations in vivo. This work reveals genes and mechanisms that contribute to S. aureus infection of macrophages, highlights differences in mutations underlying convergent phenotypes arising from in vivo and in vitro systems, and supports the relevance of S. aureus macrophage pathogenesis during chronic respiratory infection in CF. Additional studies will be needed to illuminate the exact mechanisms by which implicated mutations affect their phenotypes.

PMID:38991026 | DOI:10.1371/journal.ppat.1012394

Eur Arch Paediatr Dent. 2024 Jul 11. doi: 10.1007/s40368-024-00885-8. Online ahead of print.

ABSTRACT

PURPOSE: Good oral health is important for children and adolescents with cystic fibrosis (CF). The purpose of this scoping review is to describe the existing evidence base regarding oral health in children and adolescents with CF and provide recommendations for future research.

METHODS: Using a scoping review framework, a comprehensive search was undertaken using medline, embase, and PubMed. The search strategy included broad terms relating to CF, oral health, and children and adolescents and included only papers written in English.

RESULTS: 61 articles were included. Topics investigated included dental caries, enamel defects, periodontal health, dental staining, oral health related quality of life, dental management, and dental development of children and adolescents with CF.

CONCLUSION: Dental outcomes of children and adolescents with CF differ from the healthy population. The current literature describing dental health in children and adolescents with CF includes predominately descriptive analyses. A shift to hypothesis-based studies to explore causal relationships that explain the differences in dental outcomes seen in the CF population offers an opportunity to better understand the problems faced by children and adolescents with CF. Research that actively engages stakeholders, including children and adolescents with CF and their families will enable evidence-based recommendations to improve their oral health.

PMID:38990412 | DOI:10.1007/s40368-024-00885-8

Pediatr Pulmonol. 2024 Jul 11. doi: 10.1002/ppul.27173. Online ahead of print.

NO ABSTRACT

PMID:38990108 | DOI:10.1002/ppul.27173

Int Forum Allergy Rhinol. 2024 Jul 11. doi: 10.1002/alr.23413. Online ahead of print.

ABSTRACT

Chitosan is a promising drug delivery vector for therapeutics owing to its biocompatibility. Once crosslinked with chitosan, prolonged drug release was noted regardless of hydrophilicity. Hydrophilic drugs may require different strategies to obtain a sustained release profile.

PMID:38990106 | DOI:10.1002/alr.23413

Pediatr Pulmonol. 2024 Jul 11. doi: 10.1002/ppul.27175. Online ahead of print.

ABSTRACT

BACKGROUND: Racial and ethnic disparities in pediatric lung transplantation (LTx) related to the shifting cystic fibrosis (CF) population receiving highly effective modulator therapy (HEMT) has not been well investigated.

METHODS: The UNOS Registry was queried for patients age 1-25 years undergoing bilateral LTx between 1 January 2012 and 31 December 2021. Race and ethnicity were classified as non-Hispanic White, non-Hispanic Black, Hispanic, or none of the above. The primary outcome was posttransplant mortality. Trends in the association between race/ethnicity and mortality were examined using transplant year as a continuous variable and stratifying year based on introduction of HEMT (triple combination therapy) in November 2019.

RESULTS: In the study sample (N = 941), 7% of patients were non-Hispanic Black, 15% were Hispanic, and 2% were some other racial or ethnic group. One hundred (11%) received LTx after approval of triple combination therapy, and 407 (43%) died during follow-up. We identified a statistically significant disparity in mortality hazard (hazard ratio: 1.91; 95% confidence interval: 1.31, 2.80) in non-Hispanic Black compared to non-Hispanic White patients in the pre-triple combination therapy era.

CONCLUSIONS: We found higher mortality hazard among non-Hispanic Black compared to non-Hispanic White children undergoing LTx in the United States. Further monitoring of LTx outcomes to identify and address disparities is needed in the current era of triple combination therapy for CF.

PMID:38990104 | DOI:10.1002/ppul.27175

Pediatr Pulmonol. 2024 Jul 11. doi: 10.1002/ppul.27160. Online ahead of print.

ABSTRACT

BACKGROUND: New York (NY) State implemented a new cystic fibrosis (CF) newborn screen (NBS) algorithm in December 2017 with improvement in positive predictive value and unanticipated increased identification of infants with cystic fibrosis transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS). Repeat sweat testing is recommended in infants with CRMS. During the COVID-19 pandemic infants with CRMS were lost to follow up. With this quality improvement (QI) initiative, we aimed to perform repeat sweat testing in 25% of infants lost to follow up. We also describe consensus recommendations for CRMS from the NY CF NBS Consortium.

METHODS: Our QI team identified the primary drivers contributing to absent follow up, outreached to families, and created a questionnaire to evaluate parental understanding of CRMS using QI-based strategies.

RESULTS: Of 350 infants diagnosed with CRMS during the study period, 179 (51.1%) infants were lost to follow up. A total of 31 (17.3%) were scheduled for repeat sweat tests and followed up at CF Centers. Families reported high satisfaction with the CRMS knowledge questionnaire.

CONCLUSIONS: With this QI-based approach, we effectively recaptured infants with CRMS previously lost to follow up during the COVID-19 pandemic. Ongoing concerns about infection risk and lack of understanding on the part of families and pediatricians likely contributed to patients with CRMS lost to follow up. Consensus recommendations for CRMS include annual visits with repeat sweat testing until 2-6 years of age and education for adolescents about clinical and reproductive implications of CRMS.

PMID:38990093 | DOI:10.1002/ppul.27160

Antimicrob Agents Chemother. 2024 Jul 11:e0002924. doi: 10.1128/aac.00029-24. Online ahead of print.

ABSTRACT

Mycobacterium abscessus infections are emerging in cystic fibrosis patients, and treatment success rate in these patients is only 33% due to extreme antibiotic resistance. Thus, new treatment options are essential. An interesting target could be Lsr2, a nucleoid-associated protein involved in mycobacterial virulence. Zafirlukast is a Food and Drug Administration (FDA)-approved drug against asthma that was shown to bind Lsr2. In this study, zafirlukast treatment is shown to reduce M. abscessus growth, with a minimal inhibitory concentration of 16 µM and a bactericidal concentration of 64 µM in replicating bacteria only. As an initial response, DNA condensation, a known stress response of mycobacteria, occurs after 1 h of treatment with zafirlukast. During continued zafirlukast treatment, the morphology of the bacteria alters and the structural integrity of the bacteria is lost. After 4 days of treatment, reduced viability is measured in different culture media, and growth of M. abscessus is reduced in a dose-dependent manner. Using transmission electron microscopy, we demonstrated that the hydrophobic multilayered cell wall and periplasm are disorganized and ribosomes are reduced in size and relocalized. In summary, our data demonstrate that zafirlukast alters the morphology of M. abscessus and is bactericidal at 64 µM. The bactericidal concentration of zafirlukast is relatively high, and it is only effective on replicating bacteria but as zafirlukast is an FDA-approved drug, and currently used as an anti-asthma treatment, it could be an interesting drug to further study in in vivo experiments to determine whether it could be used as an antibiotic for M. abscessus infections.

PMID:38990015 | DOI:10.1128/aac.00029-24

mBio. 2024 Jul 11:e0035524. doi: 10.1128/mbio.00355-24. Online ahead of print.

ABSTRACT

The Type VI secretion system (T6SS) is a multicomponent apparatus, present in many Gram-negative bacteria, which can inhibit bacterial prey in various ecological niches. Pseudomonas aeruginosa assembles one of its three T6SS (H1-T6SS) to respond to attacks from adjacent competing bacteria. Surprisingly, repeated assemblies of the H1-T6SS, termed dueling, were described in a monoculture in the absence of an attacker strain; however, the underlying mechanism was unknown. Here, we explored the role of H2-T6SS of P. aeruginosa in triggering H1-T6SS assembly. We show that H2-T6SS inactivation in P. aeruginosa causes a significant reduction in H1-T6SS dueling and that H2-T6SS activity directly triggers retaliation by the H1-T6SS. Intraspecific competition experiments revealed that elimination of H2-T6SS in non-immune prey cells conferred protection from H1-T6SS. Moreover, we show that the H1-T6SS response is triggered independently of the characterized lipase effectors of the H2-T6SS, as well as those of Acinetobacter baylyi and Vibrio cholerae. Our results suggest that H1-T6SS response to H2-T6SS in P. aeruginosa can impact intraspecific competition, particularly when the H1-T6SS effector-immunity pairs differ between strains, and could determine the outcome of multistrain colonization.IMPORTANCEThe opportunistic pathogen Pseudomonas aeruginosa harbors three different Type VI secretion systems (H1, H2, and H3-T6SS), which can translocate toxins that can inhibit bacterial competitors or inflict damage to eukaryotic host cells. Unlike the unregulated T6SS assembly in other Gram-negative bacteria, the H1-T6SS in P. aeruginosa is precisely assembled as a response to various cell damaging attacks from neighboring bacterial cells. Surprisingly, it was observed that neighboring P. aeruginosa cells repeatedly assemble their H1-T6SS toward each other. Mechanisms triggering this "dueling" behavior between sister cells were unknown. In this report, we used a combination of microscopy, genetic and intraspecific competition experiments to show that H2-T6SS initiates H1-T6SS dueling. Our study highlights the interplay between different T6SS clusters in P. aeruginosa, which may influence the outcomes of multistrain competition in various ecological settings such as biofilm formation and colonization of cystic fibrosis lungs.

PMID:38990002 | DOI:10.1128/mbio.00355-24

Nat Biomed Eng. 2024 Jul 10. doi: 10.1038/s41551-024-01233-3. Online ahead of print.

ABSTRACT

Prime editing (PE) enables precise and versatile genome editing without requiring double-stranded DNA breaks. Here we describe the systematic optimization of PE systems to efficiently correct human cystic fibrosis (CF) transmembrane conductance regulator (CFTR) F508del, a three-nucleotide deletion that is the predominant cause of CF. By combining six efficiency optimizations for PE-engineered PE guide RNAs, the PEmax architecture, the transient expression of a dominant-negative mismatch repair protein, strategic silent edits, PE6 variants and proximal 'dead' single-guide RNAs-we increased correction efficiencies for CFTR F508del from less than 0.5% in HEK293T cells to 58% in immortalized bronchial epithelial cells (a 140-fold improvement) and to 25% in patient-derived airway epithelial cells. The optimizations also resulted in minimal off-target editing, in edit-to-indel ratios 3.5-fold greater than those achieved by nuclease-mediated homology-directed repair, and in the functional restoration of CFTR ion channels to over 50% of wild-type levels (similar to those achieved via combination treatment with elexacaftor, tezacaftor and ivacaftor) in primary airway cells. Our findings support the feasibility of a durable one-time treatment for CF.

PMID:38987629 | DOI:10.1038/s41551-024-01233-3

J Cyst Fibros. 2024 Jul 9:S1569-1993(24)00789-6. doi: 10.1016/j.jcf.2024.07.004. Online ahead of print.

ABSTRACT

BACKGROUND: Lung inflammation is associated with tissue damage in cystic fibrosis (CF). LAU-7b, a novel oral drug candidate, was shown to control inflammation and stabilize CFTR protein in the epithelial membrane during inflammatory stress in preclinical models of CF.

METHODS: A double-blind, randomized, placebo-controlled Phase 2 study was conducted to evaluate efficacy and safety of LAU-7b in adults with CF. LAU-7b or placebo was administered over 24 weeks as six 21-day treatment cycles each separated by 7 days. The primary efficacy endpoint was the absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) at 24 weeks.

RESULTS: A total of 166 subjects received at least one dose of study drug (Intent-To-Treat population, ITT), of which 122 received ≥5 treatment cycles (Per-Protocol population, PP). Both treatment arms showed a mean lung function loss at 24 weeks of 1.18 ppFEV1 points with LAU-7b and 1.95 ppFEV1 with placebo, a 0.77 ppFEV1 (40 s) difference, p=0.345, and a 0.95 ppFEV1 (49 %) difference in the same direction in PP population, p=0.263. Primary analysis of mean ppFEV1 through 24 weeks showed differences of 1.01 and 1.23 ppFEV1, in the ITT (65 % less loss, p=0.067) and PP populations (78 % less loss, reaching statistical significance p=0.049), respectively. LAU-7b had an acceptable safety profile.

CONCLUSION: Although the study did not meet its primary efficacy endpoint in the ITT population, LAU-7b was generally well tolerated and showed evidence of preservation of lung function to support further development.

PMID:38987119 | DOI:10.1016/j.jcf.2024.07.004

J Asthma. 2024 Jul 10:1-12. doi: 10.1080/02770903.2024.2376919. Online ahead of print.

ABSTRACT

In the field of severe asthma, the concept of disease control has recently been integrated by the one of clinical remission. With this new concept, we move on to analyze the efficacy of therapy on multiple parameters simultaneously, starting with the mandatory discontinuation of the systemic glucocorticoids, to which is added the effect on exacerbations, respiratory function, and symptoms control. The Italian severe asthma registry SANI (Severe Asthma Network Italy) drafted criteria for the definition of disease remission, allowing patients to be classified into two groups, partial and complete remission. The greater dynamism of the definition, provided by SANI, allows us to hypothesize its practical use, concerning therapy management of severe asthma patients, starting from the level of remission, with the aim to facilitate the clinical decision on replacement, continuation or modulation of patients' therapy.

PMID:38984764 | DOI:10.1080/02770903.2024.2376919

J Sci Food Agric. 2024 Jul 10. doi: 10.1002/jsfa.13732. Online ahead of print.

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) patients frequently experience gut microbiota dysbiosis. Probiotic supplementation is a potential therapeutic approach to modify gut microbiota and improve CF management through the gut-lung axis. The aim of this study was to investigate the effect of Lactobacillus reuteri supplementation on pulmonary function test, respiratory symptoms and growth in CF patients.

METHODS: A randomized, placebo-controlled clinical trial was carried out on 40 children with CF aged from 6 to 20 years. Participants were designated to receive either L. reuteri or placebo daily for 4 months. Pulmonary function tests, weight, height and body mass index (BMI) z-scores were measured pre and post treatment.

RESULTS: The median baseline BMI of the patients was 16.28 kg m-2. A significant change in the probiotic group's BMI z-score after the study period was observed (P = 0.034) but not for weight and height z-scores (P > 0.05). After treatment, Pseudomonas aeruginosa grew in sputum cultures of seven in the placebo and one patient in the intervention group (P = 0.03) while at baseline it grew in the sputum of four patients in each group. There was no significant difference in forced expiratory volume in the first second, forced expiratory flow at 25-75% or forced vital capacity change between the two groups after the treatment period (P > 0.05). Additionally, no significant differences were found in pulmonary exacerbations, hospitalization frequencies or COVID-19 infection between the two groups during the study (P > 0.05).

CONCLUSION: The results suggest that L. reuteri supplementation may impact the growth of severely malnourished CF patients. Furthermore, it may be concluded that this strain might reduce P. aeruginosa in the sputum culture of CF patients. © 2024 Society of Chemical Industry.

PMID:38982876 | DOI:10.1002/jsfa.13732