Microorganisms. 2023 Feb 9;11(2):442. doi: 10.3390/microorganisms11020442.

ABSTRACT

Stenotrophomonas maltophilia is a clinically relevant bacterial pathogen, particularly in cystic fibrosis (CF) patients. Despite the well-known ability to form biofilms inherently resistant to antibiotics and host immunity, many aspects involved in S. maltophilia biofilm formation are yet to be elucidated. In the present study, a proteomic approach was used to elucidate the differential protein expression patterns observed during the planktonic-to-biofilm transition of S. maltophilia Sm126, a strong biofilm producer causing chronic infection in a CF patient, to identify determinants potentially associated with S. maltophilia biofilm formation. In all, 57 proteins were differentially (3-fold; p < 0.01) expressed in biofilm cells compared with planktonic counterparts: 38 were overexpressed, and 19 were down-expressed. It is worth noting that 34 proteins were exclusively found in biofilm, mainly associated with quorum sensing-mediated intercellular communication, augmented glycolysis, amino acid metabolism, biosynthesis of secondary metabolites, phosphate signaling, response to nutrient starvation, and general stress. Further work is warranted to evaluate if these proteins can be suitable targets for developing anti-biofilm strategies effective against S. maltophilia.

PMID:36838406 | DOI:10.3390/microorganisms11020442

Life (Basel). 2023 Feb 7;13(2):459. doi: 10.3390/life13020459.

ABSTRACT

BACKGROUND: Initial evidence supports the hypothesis that patients with non-cystic fibrosis bronchiectasis (NCFB) have a higher risk of lung cancer. We systematically reviewed the available literature to define the characteristics of lung malignancies in patients with bronchiectasis and the characteristics of patients who develop bronchiectasis-associated lung cancer.

METHOD: This study was performed based on the PRISMA guidelines. The review protocol was registered in PROSPERO.

RESULTS: The frequency rates of lung cancer in patients with NCFB ranged from 0.93% to 8.0%. The incidence rate was 3.96. Cancer more frequently occurred in the elderly and males. Three studies found an overall higher risk of developing lung cancer in the NCFB population compared to the non-bronchiectasis one, and adenocarcinoma was the most frequently reported histological type. The effect of the co-existence of NCFB and COPD was unclear.

CONCLUSIONS: NCFB is associated with a higher risk of developing lung cancer than individuals without NCFB. This risk is higher for males, the elderly, and smokers, whereas concomitant COPD's effect is unclear.

PMID:36836816 | DOI:10.3390/life13020459

J Fungi (Basel). 2023 Feb 8;9(2):222. doi: 10.3390/jof9020222.

ABSTRACT

Aspergillus fumigatus is an opportunistic fungal pathogen capable of inducing chronic and acute infection in susceptible patients. A. fumigatus interacts with numerous bacteria that compose the microbiota of the lung, including Pseudomonas aeruginosa and Klebsiella pneumoniae, both of which are common isolates from cystic fibrosis sputum. Exposure of A. fumigatus to K. pneumoniae culture filtrate reduced fungal growth and increased gliotoxin production. Qualitative proteomic analysis of the K. pneumoniae culture filtrate identified proteins associated with metal sequestering, enzymatic degradation and redox activity, which may impact fungal growth and development. Quantitative proteomic analysis of A. fumigatus following exposure to K. pneumoniae culture filtrate (25% v/v) for 24 h revealed a reduced abundance of 1,3-beta-glucanosyltransferase (-3.97 fold), methyl sterol monooxygenase erg25B (-2.9 fold) and calcium/calmodulin-dependent protein kinase (-4.2 fold) involved in fungal development, and increased abundance of glutathione S-transferase GliG (+6.17 fold), non-ribosomal peptide synthase GliP (+3.67 fold), O-methyltransferase GliM (+3.5 fold), gamma-glutamyl acyltransferase GliK (+2.89 fold) and thioredoxin reductase GliT (+2.33 fold) involved in gliotoxin production. These results reveal that exposure of A. fumigatus to K. pneumoniae in vivo could exacerbate infection and negatively impact patient prognosis.

PMID:36836336 | DOI:10.3390/jof9020222

J Fungi (Basel). 2023 Feb 6;9(2):212. doi: 10.3390/jof9020212.

ABSTRACT

The incidence of invasive sino-pulmonary diseases due to non-Aspergillus hyaline molds is increasing due to an enlarging and evolving population of immunosuppressed hosts as well as improvements in the capabilities of molecular-based diagnostics. Herein, we review the following opportunistic pathogens known to cause sinopulmonary disease, the most common manifestation of hyalohyphomycosis: Fusarium spp., Scedosporium spp., Lomentospora prolificans, Scopulariopsis spp., Trichoderma spp., Acremonium spp., Paecilomyces variotii, Purpureocillium lilacinum, Rasamsonia argillacea species complex, Arthrographis kalrae, and Penicillium species. To facilitate an understanding of the epidemiology and clinical features of sino-pulmonary hyalohyphomycoses in the context of host immune impairment, we utilized a host-based approach encompassing the following underlying conditions: neutropenia, hematologic malignancy, hematopoietic and solid organ transplantation, chronic granulomatous disease, acquired immunodeficiency syndrome, cystic fibrosis, and healthy individuals who sustain burns, trauma, or iatrogenic exposures. We further summarize the pre-clinical and clinical data informing antifungal management for each pathogen and consider the role of adjunctive surgery and/or immunomodulatory treatments to optimize patient outcome.

PMID:36836326 | DOI:10.3390/jof9020212

J Fungi (Basel). 2023 Jan 24;9(2):158. doi: 10.3390/jof9020158.

ABSTRACT

The detection of Scedosporium/Lomentospora is still based on non-standardized low-sensitivity culture procedures. This fact is particularly worrying in patients with cystic fibrosis (CF), where these fungi are the second most common filamentous fungi isolated, because a poor and delayed diagnosis can worsen the prognosis of the disease. To contribute to the discovery of new diagnostic strategies, a rapid serological dot immunobinding assay (DIA) that allows the detection of serum IgG against Scedosporium/Lomentospora in less than 15 min was developed. A crude protein extract from the conidia and hyphae of Scedosporium boydii was employed as a fungal antigen. The DIA was evaluated using 303 CF serum samples (162 patients) grouped according to the detection of Scedosporium/Lomentospora in the respiratory sample by culture, obtaining a sensitivity and specificity of 90.48% and 79.30%, respectively; positive and negative predictive values of 54.81% and 96.77%, and an efficiency of 81.72%. The clinical factors associated with the results were also studied using a univariate and a multivariate analysis, which showed that Scedosporium/Lomentospora positive sputum, elevated anti-Aspergillus serum IgG and chronic Pseudomonas aeruginosa infection were significantly associated with a positive result in DIA, while Staphylococcus aureus positive sputum showed a negative association. In conclusion, the test developed can offer a complementary, rapid, simple and sensitive method to contribute to the diagnosis of Scedosporium/Lomentospora in patients with CF.

PMID:36836272 | DOI:10.3390/jof9020158

J Clin Med. 2023 Feb 16;12(4):1562. doi: 10.3390/jcm12041562.

ABSTRACT

BACKGROUND: In COVID-19 patients non-invasive-positive-pressure-ventilation (NIPPV) has held a challenging role to reduce mortality and the need for invasive mechanical ventilation (IMV). The aim of this study was to compare the characteristics of patients admitted to a Medical Intermediate Care Unit for acute respiratory failure due to SARS-CoV-2 pneumonia throughout four pandemic waves.

METHODS: The clinical data of 300 COVID-19 patients treated with continuous positive airway pressure (CPAP) were retrospectively analysed, from March-2020 to April-2022.

RESULTS: Non-survivors were older and more comorbid, whereas patients transferred to ICU were younger and had fewer pathologies. Patients were older (from 65 (29-91) years in I wave to 77 (32-94) in IV, p < 0.001) and with more comorbidities (from Charlson's Comorbidity Index = 3 (0-12) in I to 6 (1-12) in IV, p < 0.001). No statistical difference was found for in-hospital mortality (33.0%, 35.8%, 29.6% and 45.9% in I, II, III and IV, p = 0.216), although ICU-transfers rate decreased from 22.0% to 1.4%.

CONCLUSIONS: COVID-19 patients have become progressively older and with more comorbidities even in critical care area; from risk class analyses by age and comorbidity burden, in-hospital mortality rates remain high and are thus consistent over four waves while ICU-transfers have significantly reduced. Epidemiological changes need to be considered to improve the appropriateness of care.

PMID:36836094 | DOI:10.3390/jcm12041562

J Clin Med. 2023 Feb 12;12(4):1468. doi: 10.3390/jcm12041468.

ABSTRACT

The introduction of mutation-specific therapy led to a revolution in cystic fibrosis (CF) care. These advances in CF therapies have changed the disease profile from a severe incurable disease with limited survival to a treatable disease with improved quality of life and survival into adulthood. CF patients are now able to plan their future, including marriage and parenthood. Side by side with the optimism, new issues and concerns are arising, including fertility and preparation for pregnancy, maternal and fetal care during pregnancy, and post-partum care. While cystic fibrosis transmembrane regulator (CFTR) modulators show promising results for improving CF lung disease, data on their safety in pregnancy are still limited. We performed a literature review on pregnancy in CF from the past, with the first described pregnancy in 1960, through the current fascinating changes in the era of CFTR modulators, to ongoing studies and future directions. Current advances in knowledge give hope for improved outcomes of pregnancy, towards the best possible prognosis for the mother and for the baby.

PMID:36836003 | DOI:10.3390/jcm12041468

Int J Mol Sci. 2023 Feb 20;24(4):4252. doi: 10.3390/ijms24044252.

ABSTRACT

Correct protein folding is the basis of cellular well-being; thus, accumulation of misfolded proteins within the endoplasmic reticulum (ER) leads to an imbalance of homeostasis that causes stress to the ER. Various studies have shown that protein misfolding is a significant factor in the etiology of many human diseases, including cancer, diabetes, and cystic fibrosis. Misfolded protein accumulation in the ER triggers a sophisticated signal transduction pathway, the unfolded protein response (UPR), which is controlled by three proteins, resident in ER: IRE1α, PERK, and ATF6. Briefly, when ER stress is irreversible, IRE1α induces the activation of pro-inflammatory proteins; PERK phosphorylates eIF2α which induces ATF4 transcription, while ATF6 activates genes encoding ER chaperones. Reticular stress causes an alteration of the calcium homeostasis, which is released from the ER and taken up by the mitochondria, leading to an increase in the oxygen radical species production, and consequently, to oxidative stress. Accumulation of intracellular calcium, in combination with lethal ROS levels, has been associated with an increase of pro-inflammatory protein expression and the initiation of the inflammatory process. Lumacaftor (Vx-809) is a common corrector used in cystic fibrosis treatment which enhances the folding of mutated F508del-CFTR, one of the most prevalent impaired proteins underlying the disease, promoting a higher localization of the mutant protein on the cell membrane. Here, we demonstrate that this drug reduces the ER stress and, consequently, the inflammation that is caused by such events. Thus, this molecule is a promising drug to treat several pathologies that present an etiopathogenesis due to the accumulation of protein aggregates that lead to chronic reticular stress.

PMID:36835664 | DOI:10.3390/ijms24044252

Int J Mol Sci. 2023 Feb 17;24(4):4052. doi: 10.3390/ijms24044052.

ABSTRACT

The interplay between airway inflammation and infection is now recognized as a major factor in the pathobiology in cystic fibrosis (CF). A proinflammatory environment is seen throughout the CF airway resulting in classic marked and enduring neutrophilic infiltrations, irreversibly damaging the lung. Although this is seen to occur early, independent of infection, respiratory microbes arising at different timepoints in life and the world environment perpetuate this hyperinflammatory state. Several selective pressures have allowed for the CF gene to persist until today despite an early mortality. Comprehensive care systems, which have been a cornerstone of therapy for the past few decades, are now revolutionized by CF transmembrane conductance regulator (CTFR) modulators. The effects of these small-molecule agents cannot be overstated and can be seen as early as in utero. For an understanding of the future, this review looks into CF studies spanning the historical and present period.

PMID:36835487 | DOI:10.3390/ijms24044052

Int J Mol Sci. 2023 Feb 16;24(4):4027. doi: 10.3390/ijms24044027.

ABSTRACT

The pancreas represents an important organ that has not been comprehensively studied in many fields. To fill this gap, many models have been generated, and traditional models have shown good performance in addressing pancreatic-related diseases, but are increasingly struggling to keep up with the need for further research due to ethical issues, genetic heterogeneity and difficult clinical translation. The new era calls for new and more reliable research models. Therefore, organoids have been proposed as a novel model for the evaluation of pancreatic-related diseases such as pancreatic malignancy, diabetes, and pancreatic cystic fibrosis. Compared with common traditional models, including 2D cell culture and gene editing mice, organoids derived from living humans or mice cause minimal harm to the donor, raise fewer ethical concerns, and reasonably address the claims of heterogeneity, which allows for the further development of pathogenesis studies and clinical trial analysis. In this review, we analyse studies on the use of pancreatic organoids in research on pancreatic-related diseases, discuss the advantages and disadvantages, and hypothesize future trends.

PMID:36835437 | DOI:10.3390/ijms24044027

Int J Mol Sci. 2023 Feb 16;24(4):4024. doi: 10.3390/ijms24044024.

ABSTRACT

Shwachman-Diamond syndrome (SDS) represents one of the most common inherited bone marrow failure syndromes and is mainly caused by SBDS gene mutations. Only supportive treatments are available, with hematopoietic cell transplantation required when marrow failure occurs. Among all causative mutations, the SBDS c.258+2T>C variant at the 5' splice site (ss) of exon 2 is one of the most frequent. Here, we investigated the molecular mechanisms underlying aberrant SBDS splicing and showed that SBDS exon 2 is dense in splicing regulatory elements and cryptic splice sites, complicating proper 5'ss selection. Studies ex vivo and in vitro demonstrated that the mutation alters splicing, but it is also compatible with tiny amounts of correct transcripts, which would explain the survival of SDS patients. Moreover, for the first time for SDS, we explored a panel of correction approaches at the RNA and DNA levels and provided experimental evidence that the mutation effect can be partially counteracted by engineered U1snRNA, trans-splicing, and base/prime editors, ultimately leading to correctly spliced transcripts (from barely detectable to 2.5-5.5%). Among them, we propose DNA editors that, by stably reverting the mutation and potentially conferring positive selection to bone-marrow cells, could lead to the development of an innovative SDS therapy.

PMID:36835434 | DOI:10.3390/ijms24044024

Int J Mol Sci. 2023 Feb 10;24(4):3570. doi: 10.3390/ijms24043570.

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection leads to a wide range of clinical manifestations and determines the need for personalized and precision medicine. To better understand the biological determinants of this heterogeneity, we explored the plasma proteome of 43 COVID-19 patients with different outcomes by an untargeted liquid chromatography-mass spectrometry approach. The comparison between asymptomatic or pauci-symptomatic subjects (MILDs), and hospitalised patients in need of oxygen support therapy (SEVEREs) highlighted 29 proteins emerged as differentially expressed: 12 overexpressed in MILDs and 17 in SEVEREs. Moreover, a supervised analysis based on a decision-tree recognised three proteins (Fetuin-A, Ig lambda-2chain-C-region, Vitronectin) that are able to robustly discriminate between the two classes independently from the infection stage. In silico functional annotation of the 29 deregulated proteins pinpointed several functions possibly related to the severity; no pathway was associated exclusively to MILDs, while several only to SEVEREs, and some associated to both MILDs and SEVEREs; SARS-CoV-2 signalling pathway was significantly enriched by proteins up-expressed in SEVEREs (SAA1/2, CRP, HP, LRG1) and in MILDs (GSN, HRG). In conclusion, our analysis could provide key information for 'proteomically' defining possible upstream mechanisms and mediators triggering or limiting the domino effect of the immune-related response and characterizing severe exacerbations.

PMID:36834989 | DOI:10.3390/ijms24043570

Int J Mol Sci. 2023 Feb 7;24(4):3260. doi: 10.3390/ijms24043260.

ABSTRACT

cAMP-phosphodiesterase 4 (PDE4) inhibitors are currently approved for the treatment of inflammatory diseases. There is interest in expanding the therapeutic application of PDE4 inhibitors to metabolic disorders, as their chronic application induces weight loss in patients and animals and improves glucose handling in mouse models of obesity and diabetes. Unexpectedly, we have found that acute PDE4 inhibitor treatment induces a temporary increase, rather than a decrease, in blood glucose levels in mice. Blood glucose levels in postprandial mice increase rapidly upon drug injection, reaching a maximum after ~45 min, and returning to baseline within ~4 h. This transient blood glucose spike is replicated by several structurally distinct PDE4 inhibitors, suggesting that it is a class effect of PDE4 inhibitors. PDE4 inhibitor treatment does not reduce serum insulin levels, and the subsequent injection of insulin potently reduces PDE4 inhibitor-induced blood glucose levels, suggesting that the glycemic effects of PDE4 inhibition are independent of changes in insulin secretion and/or sensitivity. Conversely, PDE4 inhibitors induce a rapid reduction in skeletal muscle glycogen levels and potently inhibit the uptake of 2-deoxyglucose into muscle tissues. This suggests that reduced glucose uptake into muscle tissue is a significant contributor to the transient glycemic effects of PDE4 inhibitors in mice.

PMID:36834669 | DOI:10.3390/ijms24043260

Int J Mol Sci. 2023 Feb 6;24(4):3211. doi: 10.3390/ijms24043211.

ABSTRACT

Cystic Fibrosis (CF) is a genetic disease caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. Currently, more than 2100 variants have been identified in the gene, with a large number being very rare. The approval of modulators that act on mutant CFTR protein, correcting its molecular defect and thus alleviating the burden of the disease, revolutionized the field of CF. However, these drugs do not apply to all patients with CF, especially those with rare mutations-for which there is a lack of knowledge on the molecular mechanisms of the disease and the response to modulators. In this work, we evaluated the impact of several rare putative class II mutations on the expression, processing, and response of CFTR to modulators. Novel cell models consisting of bronchial epithelial cell lines expressing CFTR with 14 rare variants were created. The variants studied are localized at Transmembrane Domain 1 (TMD1) or very close to the signature motif of Nucleotide Binding Domain 1 (NBD1). Our data show that all mutations analyzed significantly decrease CFTR processing and while TMD1 mutations respond to modulators, those localized in NBD1 do not. Molecular modeling calculations confirm that the mutations in NBD1 induce greater destabilization of CFTR structure than those in TMD1. Furthermore, the structural proximity of TMD1 mutants to the reported binding site of CFTR modulators such as VX-809 and VX-661, make them more efficient in stabilizing the CFTR mutants analyzed. Overall, our data suggest a pattern for mutation location and impact in response to modulators that correlates with the global effect of the mutations on CFTR structure.

PMID:36834620 | DOI:10.3390/ijms24043211

Int J Mol Sci. 2023 Feb 4;24(4):3092. doi: 10.3390/ijms24043092.

ABSTRACT

Chronic lung infections in cystic fibrosis (CF) patients are triggered by multidrug-resistant bacteria such as Pseudomonas aeruginosa, Achromobacter xylosoxidans, and Stenotrophomonas maltophilia. The CF airways are considered ideal sites for the colonization and growth of bacteria and fungi that favor the formation of mixed biofilms that are difficult to treat. The inefficacy of traditional antibiotics reinforces the need to find novel molecules able to fight these chronic infections. Antimicrobial peptides (AMPs) represent a promising alternative for their antimicrobial, anti-inflammatory, and immunomodulatory activities. We developed a more serum-stable version of the peptide WMR (WMR-4) and investigated its ability to inhibit and eradicate C. albicans, S. maltophilia, and A. xylosoxidans biofilms in both in vitro and in vivo studies. Our results suggest that the peptide is able better to inhibit than to eradicate both mono and dual-species biofilms, which is further confirmed by the downregulation of some genes involved in biofilm formation or in quorum-sensing signaling. Biophysical data help to elucidate its mode of action, showing a strong interaction of WMR-4 with lipopolysaccharide (LPS) and its insertion in liposomes mimicking Gram-negative and Candida membranes. Our results support the promising therapeutic application of AMPs in the treatment of mono- and dual-species biofilms during chronic infections in CF patients.

PMID:36834512 | DOI:10.3390/ijms24043092

Genes (Basel). 2023 Feb 9;14(2):449. doi: 10.3390/genes14020449.

ABSTRACT

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators represent targeted therapies directly acting on the CFTR channel. The triple therapy Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) has been demonstrated to improve lung function and quality of life in cystic fibrosis (CF) patients. However, the effects of ELX/TEZ/IVA on sleep-disordered breathing (SDB) and respiratory muscle strength are poorly studied. The aim of this study was to assess the effects of ELX/TEZ/IVA in patients with CF and severe lung disease on cardiorespiratory polygraphy parameters, maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) measures.

METHODS: patients with CF aged ≥ 12 who started treatment in a compassionate use program were retrospectively studied through the evaluation of nocturnal cardiorespiratory polygraphy parameters, MIP and MEP; and six-minute walk test (6MWT) at baseline and at months 3, 6, and 12 of treatment.

RESULTS: Nine patients (mean age 30.3 ± 6.5 years) with severe CF (mean baseline ppFEV1 34.6 ± 5.1%) were evaluated. A significant improvement in nocturnal oxygenation measured by mean SpO2 (92.4 vs. 96.4%, p < 0.05), time spent with SpO2 ≤ 90% (-12.6, -14.6, -15.2 min from baseline at months 3, 6, and 12, respectively, p < 0.05), and respiratory rate (RR) was shown, at month 12 and across the time points compared with baseline, as well as in respiratory muscle strength, although only the change in MEP was significant.

CONCLUSIONS: We provide further evidence on the efficacy of the CFTR modulators ELX/TEZ/IVA, adding information about their effect on the respiratory muscles' performance and cardiorespiratory polygraphy parameters in CF patients with severe lung disease.

PMID:36833376 | DOI:10.3390/genes14020449

Children (Basel). 2023 Feb 8;10(2):324. doi: 10.3390/children10020324.

ABSTRACT

Chronic life-limiting illnesses such as chronic kidney disease (CKD) require integral support to the families concerned in addition to medical care. Palliative care is an option to facilitate families to address future concerns, such as procedures for acute life-threatening complications, or to relieve physical and psychosocial suffering. The exact needs of patients or parents have not yet been investigated. To assess needs in supportive palliative care, we conducted a monocentric qualitative interview study. We included patients 14 to 24 years old as well as parents of younger children (below 14 years) with CKD ≥ stage 3. In total, fifteen interviews were conducted. Data were analyzed with a deductive and descriptive approach using qualitative content analysis as described by Mayring. Sociodemographic data and basic information of disease were collected using questionnaires. In contrast to caregivers, adolescents and young adults do not express worries about their own mortality or reduced life expectancy. Rather, they report about their limitations to everyday life associated with the disease, especially in the areas of school and work. They wish to live a normal life. Caregivers are concerned about the future and the disease trajectory. They also describe difficulties in balancing the management of the disease with other responsibilities such as work and healthy siblings' needs. Patients and caregivers appear to need a chance to talk about their everyday struggles and disease-related fears and concerns. Talking about their concerns and needs may help deal with their emotions and facilitate acceptance of their situation characterized by a life-limiting disease. Our study confirms the need for psychosocial support in pediatric nephrology to address the needs of the affected families. This can be offered by pediatric palliative care teams.

PMID:36832453 | DOI:10.3390/children10020324

Children (Basel). 2023 Jan 31;10(2):280. doi: 10.3390/children10020280.

ABSTRACT

CFTR-related metabolic syndrome (CRMS) is a novel diagnosis due to widespread use of and advances in the newborn screening (NBS) process for cystic fibrosis (CF) in the United States of America, allowing for the diagnosis of asymptomatic children with CF. Before 2015, a large Puerto Rican pediatric population was not screened for CF in the NBS test. Studies have shown that patients presenting with idiopathic recurrent or chronic pancreatitis have an increased frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. We present a retrospective chart review of 12 pediatric cases (n = 12) that were presented to an outpatient community clinic with clinical manifestations associated with CF. The pancreatic insufficiency prevalence (PIP) score was calculated on CFTR mutations. The mutations considered for the calculation of the PIP score were: F508del (c.1521_1523del), V201M (c.601G > A), I507del (c.1519_1521del), and L1335P (c.4004T > C). V201M mutation was classified as mild in both PIP scores, and a correlation with pancreatitis was noted. Clinical manifestations vary in cases with the V201M variant (c.601G > A). One case was diagnosed with CFTR-related disorder (CRD) and recurrent pancreatitis. It is important to consider CRMS or CRD as a differential diagnosis in the pediatric population of Puerto Rico due to the implications and increased risk of pancreatitis and other CF-related complications.

PMID:36832409 | DOI:10.3390/children10020280

Children (Basel). 2023 Jan 30;10(2):252. doi: 10.3390/children10020252.

ABSTRACT

BACKGROUND: Improved therapy in CF has led to an overall improvement in nutritional status. The objectives of our study are: to cross-sectionally assess nutritional status and serum levels of fat-soluble vitamins; to retrospectively evaluate the efficacy of modulators on nutritional status and fat-soluble vitamin levels.

METHODS: In patients younger than 2 years of age, we evaluated growth, in patients aged 2-18 years, we assessed BMI z-scores, and in adults, we assessed absolute BMI values. Levels of 25(OH)D, vitamins A, and E were measured.

RESULTS: A cross-sectional analysis was conducted on 318 patients, 109 (34.3%) with pancreatic sufficiency. Only three patients were under 2 years old. In 135 patients aged 2-18 years, the median BMI z-score was 0.11, and 5 (3.7%) patients had malnutrition (z-score ≤ 2SD). In 180 adults, the median BMI was 21.8 kg/m2. Overall, 15 (13.7%) males (M) and 18 (25.3%) females (F) were underweight (18 < BMI > 20); 3 (2.7%) M and 5 (7.0%) F had a BMI < 18. Suboptimal 25(OH)D levels were found in patients with pancreatic insufficiency. The prevalence of deficiency of vitamins A and E is low. After one year of treatment with modulators, the increase in BMI was more consistent (M: 1.58 ± 1.25 kg/m2 F: 1.77 ± 1.21 kg/m2) in elexacaftor/tezacaftor/ivacaftor (ETI)-treated patients compared with other modulators, with a significant increase in levels of all fat-soluble vitamins.

CONCLUSIONS: Malnutrition is present in a limited number of subjects. The prevalence of subjects with suboptimal 25(OH)D levels is high. ETI showed a beneficial effect on nutritional status and circulating levels of fat-soluble vitamins.

PMID:36832382 | DOI:10.3390/children10020252

Children (Basel). 2023 Jan 23;10(2):204. doi: 10.3390/children10020204.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) patients require regular airway clearance therapy (ACT). The aim of this study was to evaluate homecare therapeutic effects of a new ACT (Simeox®) added to the optimal standard of care, including home chest physiotherapy, in the treatment of clinically stable children.

METHODS: Forty pediatric CF patients (8-17 years old) with stable disease were randomized 1:1 in a single-center, prospective, open-label, cross-over trial into two groups: with or without Simeox®. Lung function (impulse oscillometry, spirometry, body plethysmography, multi-breath nitrogen washout) results, health-related quality of life, and safety were assessed during the study after 1 month of therapy at home.

RESULTS: A significant decrease in proximal airway obstruction (as supported by improvement in airway resistance at 20 Hz (R20Hz) and maximum expiratory flow at 75% of FVC (MEF75)) compared to the control group was observed after 1 month of therapy with the device. Lung-clearance index was stable in the study group, while it worsened in the control group. In addition, the device group demonstrated a significant increase in the Cystic Fibrosis Questionnaire-Revised (CFQ-R) physical score. No side effects were identified during the study.

CONCLUSIONS: Simeox® may improve drainage of the airways in children with clinically stable CF and could be an option in chronic treatment of the disease.

PMID:36832333 | DOI:10.3390/children10020204