Biomed Pharmacother. 2024 Jul 17;178:117153. doi: 10.1016/j.biopha.2024.117153. Online ahead of print.

ABSTRACT

Infectious diseases are a major threat to global health and cause millions of deaths every year, particularly in developing countries. The emergence of multidrug resistance challenges current antimicrobial treatments, inducing uncertainty in therapeutic protocols. New compounds are therefore necessary. A drug repurposing approach could play a critical role in developing new treatments used either alone or in combination with standard therapy regimens. Herein, we focused on cysteamine, an aminothiol endogenously synthesized by human cells during the degradation of coenzyme-A, which is a drug approved for the treatment of nephropathic cystinosis. Cysteamine influences many biological processes due to the presence of the highly reactive thiol group. This review provides an overview of cysteamine-mediated effects on different viruses, bacteria and parasites, with a particular focus on infections caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Mycobacterium tuberculosis, non-tuberculous mycobacteria (NTM), and Pseudomonas aeruginosa. Evidences for a potential use of cysteamine as a direct antimicrobial agent and/or a host-directed therapy, either alone or in combination with other antimicrobial drugs, are described.

PMID:39024833 | DOI:10.1016/j.biopha.2024.117153

Biol Sex Differ. 2024 Jul 18;15(1):56. doi: 10.1186/s13293-024-00633-z.

ABSTRACT

Biological sex differences exist for many airway diseases in which females have either worse or better health outcomes. Inflammatory airway diseases such as cystic fibrosis (CF) and asthma display a clear male advantage in post-puberty while a female benefit is observed in asthma during the pre-puberty years. The influence of menstrual cycle stage and pregnancy on the frequency and severity of pulmonary exacerbations in CF and asthma point to a role for sex steroid hormones, particularly estrogen, in underpinning biological sex differences in these diseases. There are many ways by which estrogen may aggravate asthma and CF involving disturbances in airway surface liquid (ASL) dynamics, inappropriate hyper-immune and allergenic responses, as well as exacerbation of pathogen virulence. The deleterious effect of estrogen on pulmonary function in CF and asthma contrasts with the female advantage observed in airway diseases characterised by pulmonary edema such as pneumonia, acute respiratory distress syndrome (ARDS) and COVID-19. Airway surface liquid hypersecretion and alveolar flooding are hallmarks of ARDS and COVID-19, and contribute to the morbidity and mortality of severe forms of these diseases. ASL dynamics encompasses the intrinsic features of the thin lining of fluid covering the airway epithelium which regulate mucociliary clearance (ciliary beat, ASL height, volume, pH, viscosity, mucins, and channel activating proteases) in addition to innate defence mechanisms (pathogen virulence, cytokines, defensins, specialised pro-resolution lipid mediators, and metabolism). Estrogen regulation of ASL dynamics contributing to biological sex differences in CF, asthma and COVID-19 is a major focus of this review.

PMID:39026347 | DOI:10.1186/s13293-024-00633-z

BMC Pulm Med. 2024 Jul 18;24(1):348. doi: 10.1186/s12890-024-03163-x.

ABSTRACT

BACKGROUND: Outcomes for individuals with cystic fibrosis (CF) have improved due to highly effective modulator therapy (HEMT). However, lung transplant (LTx) remains an important treatment for people with advanced lung disease. This study assessed attitudes and knowledge about LTx in the HEMT era.

METHODS: All patients from the University of Washington CF clinic were surveyed March 25-May 30, 2020. Questions addressed self-rated LTx preparedness and knowledge, as well as barriers and facilitators to discussing LTx. Demographic and clinical data were extracted from the electronic health record.

RESULTS: There were 159/224 (71%) responses. Respondents had a median forced expiratory volume in one second (FEV1) of 70%, and 142 (89%) were on modulatory therapy. One hundred thirteen (71%) respondents felt that it was moderately or very important to be prepared to make decisions about LTx, though only 56 (35%) felt moderately or very prepared. Only 83 (30%) and 47 (52%) participants correctly answered questions about life expectancy and improved quality of life after LTx, respectively. Respondents with Medicaid insurance less frequently answered questions correctly. The most common barriers to discussing LTx were fear of being a burden on loved ones for 58 respondents (36%) and cost of LTx for 46 (29%). Most participants (94%) trusted their CF doctor, and 75% of participants selected trust as a facilitator for LTx discussions.

CONCLUSIONS: Many individuals with CF, especially those with lower socioeconomic status, lacked knowledge and did not feel very prepared for decisions about LTx. Earlier education and discussions about LTx represent an area for improvement in CF care.

PMID:39026320 | DOI:10.1186/s12890-024-03163-x

Turk J Pediatr. 2024 Jul 11;66(3):297-308. doi: 10.24953/turkjpediatr.2024.4516.

ABSTRACT

BACKGROUND: The lung clearance index (LCI) is a sensitive lung function index that is used to detect early lung disease changes in children with cystic fibrosis (CF). This study aimed to define the predictive role of baseline LCI, along with other potential factors on the change in forced expiratory volume in one second (FEV1) during one-year follow-up in CF patients who had a percent predicted (pp) FEV1≥80.

METHODS: LCI was concurrently performed on 57 CF patients who had ppFEV1 ≥80 at month zero. The ppFEV1 decline was evaluated prospectively during the one year follow up. The primary outcome of ppFEV1 decline in the study group in one year was dichotomized according to the median value for the decline in ppFEV1, which was 3.7. The LCI value predicting ppFEV1 decline at the end of one year was calculated with receiver operating characteristic curve analysis. Regression analysis was performed. Furthermore, a decision tree was constructed using classification and regression tree methods to better define the potential effect of confounders on the ppFEV1 decline.

RESULTS: The LCI value for predicting ppFEV1 decline >3.7% at the end of one year was 8.2 (area under the curve: 0.80) Multivariable regression analysis showed that the absence of the F508del mutation in at least one allele, LCI >8.2 and initial FEV1 z-score were predictors of a ppFEV1 decline >3.7 (p<0.001). Factors altering ppFEV1 decline>3.7% at the end of one-year evaluated by decision trees were as follows: initial FEV1 z-score, type of CFTR mutation, LCI value and initial weight-for-age z-score.

CONCLUSIONS: LCI is sensitive for predicting ppFEV1 decline in patients with ppFEV1 ≥80 along with the initial FEV1-z-score and type of CFTR mutation.

PMID:39024602 | DOI:10.24953/turkjpediatr.2024.4516

Turk J Pediatr. 2024 Jul 11;66(3):309-322. doi: 10.24953/turkjpediatr.2024.4581.

ABSTRACT

BACKGROUND: There is a need to identify the complex interplay between various physiological mechanisms in primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). The study investigated the interaction between respiratory function, exercise capacity, muscle strength, and inflammatory and oxidant/antioxidant responses in patients with PCD and CF.

METHODS: The study included 30 PCD patients, 30 CF patients, and 29 age and sex-matched healthy subjects. Exercise capacity was assessed using the modified shuttle walk test (MSWT). Handgrip strength (HGS) was used to evaluate general muscle strength. Oxidative stress-inflammatory parameters were also assessed. Pulmonary function test was performed by spirometry. Regarding the forced expiratory volume in 1 second (FEV1) z-score, patients with PCD and CF were subdivided into normal, mild, and severe/moderate groups.

RESULTS: Forced vital capacity (FVC) z-scores were lower in PCD and CF patients than controls. FEV1, FEV1/FVC, peak expiratory flow (PEF), and forced mid expiratory flow (FEF25-75%) z-scores were lower in PCD than in the other groups. HGS was lower in both mild PCD and normal CF patients relative to the controls. MSWT distance was lower in severe/moderate PCD patients than controls. Catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels did not differ significantly among the study groups, but superoxide dismutase (SOD) level in severe/moderate PCD, and glutathione (GSH) level in normal CF were higher than in controls. Interleukin-6 (IL-6) level was higher in patients with normal PCD and CF compared to the controls. IL-1β level was higher in PCD compared to controls. Additionally, correlations among these parameters were also determined in some patient groups.

CONCLUSION: Homeostasis related to respiratory function, aerobic performance, muscle strength, inflammatory response, and oxidant/antioxidant balance were affected in PCD and CF. Evaluating these mechanisms together may contribute to elucidating the pathophysiology of these rare diseases.

PMID:39024596 | DOI:10.24953/turkjpediatr.2024.4581

PLoS One. 2024 Jul 18;19(7):e0304425. doi: 10.1371/journal.pone.0304425. eCollection 2024.

ABSTRACT

COVID-19 caused by SARS-CoV-2 is a global health issue. It is yet a severe risk factor to the patients, who are also suffering from one or more chronic diseases including different lung diseases. In this study, we explored common molecular signatures for which SARS-CoV-2 infections and different lung diseases stimulate each other, and associated candidate drug molecules. We identified both SARS-CoV-2 infections and different lung diseases (Asthma, Tuberculosis, Cystic Fibrosis, Pneumonia, Emphysema, Bronchitis, IPF, ILD, and COPD) causing top-ranked 11 shared genes (STAT1, TLR4, CXCL10, CCL2, JUN, DDX58, IRF7, ICAM1, MX2, IRF9 and ISG15) as the hub of the shared differentially expressed genes (hub-sDEGs). The gene ontology (GO) and pathway enrichment analyses of hub-sDEGs revealed some crucial common pathogenetic processes of SARS-CoV-2 infections and different lung diseases. The regulatory network analysis of hub-sDEGs detected top-ranked 6 TFs proteins and 6 micro RNAs as the key transcriptional and post-transcriptional regulatory factors of hub-sDEGs, respectively. Then we proposed hub-sDEGs guided top-ranked three repurposable drug molecules (Entrectinib, Imatinib, and Nilotinib), for the treatment against COVID-19 with different lung diseases. This recommendation is based on the results obtained from molecular docking analysis using the AutoDock Vina and GLIDE module of Schrödinger. The selected drug molecules were optimized through density functional theory (DFT) and observing their good chemical stability. Finally, we explored the binding stability of the highest-ranked receptor protein RELA with top-ordered three drugs (Entrectinib, Imatinib, and Nilotinib) through 100 ns molecular dynamic (MD) simulations with YASARA and Desmond module of Schrödinger and observed their consistent performance. Therefore, the findings of this study might be useful resources for the diagnosis and therapies of COVID-19 patients who are also suffering from one or more lung diseases.

PMID:39024368 | DOI:10.1371/journal.pone.0304425

PLoS One. 2024 Jul 18;19(7):e0305832. doi: 10.1371/journal.pone.0305832. eCollection 2024.

ABSTRACT

Understanding the mechanisms that underlie de novo mutations (DNMs) can be essential for interpreting human evolution, including aspects such as rapidly diverging genes, conservation of non-coding regulatory elements, and somatic DNA adaptation, among others. DNM accumulation in Homo sapiens is often limited to evaluation of human trios or quads across a single generation. Moreover, human SNPs in exons, pseudogenes, or other non-coding elements can be ancient and difficult to date, including polymorphisms attributable to founder effects and identity by descent. In this report, we describe multigenerational evolution of a human coding locus devoid of natural selection, and delineate patterns and principles by which DNMs have accumulated over the past few thousand years. We apply a data set comprising cystic fibrosis transmembrane conductance regulator (CFTR) alleles from 2,393 individuals homozygous for the F508del defect. Additional polymorphism on the F508del background diversified subsequent to a single mutational event during recent human history. Because F508del CFTR is without function, SNPs observed on this haplotype are effectively attributable to factors that govern accumulating de novo mutations. We show profound enhancement of transition, synonymous, and positionally repetitive polymorphisms, indicating appearance of DNMs in a manner evolutionarily designed to protect protein coding DNA against mutational attrition while promoting diversity.

PMID:39024311 | DOI:10.1371/journal.pone.0305832

Mycopathologia. 2024 Jul 18;189(4):68. doi: 10.1007/s11046-024-00870-1.

ABSTRACT

CONTEXT: Allergic bronchopulmonary mycoses (ABPM) can be due to molds other than Aspergillus fumigatus in patients with cystic fibrosis (pwCF). We aimed to develop immunoassays for the detection of specific IgE (sIgE) directed against five fungal species involved in ABPM: Aspergillus terreus, Scedosporium apiospermum, Lomentospora prolificans, Rasamsonia argillacea, and Exophiala dermatitidis.

MATERIALS AND METHODS: Serum samples (n = 356) from 238 pwCF, collected in eight CF care centers in France, Germany, and Italy, were analyzed by dissociated enhanced lanthanide fluorescent immunoassay (DELFIA®) to assess levels of sIgE directed against antigenic extracts of each fungus. Clinical, biological, and radiological data were collected for each episode. One hundred serum samples from healthy blood donors were used as controls. Sera were classified into four groups depending on the level of sIgE according to the quartile repartition calculated for the pwCF population. A score of 4 for values above the 3rd quartile corresponds to an elevated level of sIgE.

RESULTS: PwCF showed higher levels of sIgE than controls. Based on criteria from the ABPA-ISHAM working group, with an additional criterion of "a sIgE score of 4 for at least one non-A. fumigatus mold", we were able to diagnose six cases of ABPM.

CONCLUSIONS: Using 417 IU/mL as the threshold for total IgE and the same additional criterion, we identified seven additional pwCF with "putative ABPM". Detection of sIgE by DELFIA® showed good analytical performance and supports the role played by non-A. fumigatus molds in ABPM. However, commercially available kits usable in routine practice are needed to improve the diagnosis of ABPM.

PMID:39023843 | DOI:10.1007/s11046-024-00870-1

Pediatr Pulmonol. 2024 Jul 18. doi: 10.1002/ppul.27180. Online ahead of print.

ABSTRACT

INTRODUCTION: Major methodological issues with the existing algorithm (WBreath) used for the analysis of speed-of-sound-based infant sulfur hexafluoride (SF6) multiple-breath washout (MBW) measurements lead to implausible results and complicate the comparison between different age groups and centers.

METHODS: We developed OASIS-a novel algorithm to analyze speed-of-sound-based infant SF6 MBW measurements. This algorithm uses known context of the measurements to replace the dependence of WBreath on model input parameters. We validated the functional residual capacity (FRC) measurement accuracy of this new algorithm in vitro, and investigated its use in existing infant MBW data sets from different infant cohorts from Switzerland and South Africa.

RESULTS: In vitro, OASIS managed to outperform WBreath at FRC measurement accuracy, lowering mean (SD) absolute error from 5.1 (3.2) % to 2.1 (1.6) % across volumes relevant for the infant age range, in variable temperature, respiratory rate, tidal volume and ventilation inhomogeneity conditions. We showed that changes in the input parameters to WBreath had a major impact on MBW results, a methodological drawback which does not exist in the new algorithm. OASIS produced more plausible results than WBreath in longitudinal tracking of lung clearance index (LCI), provided improved measurement stability in LCI over time, and improved comparability between centers.

DISCUSSION: This new algorithm represents a meaningful advance in obtaining results from a legacy system of lung function measurement by allowing a single method to analyze measurements from different age groups and centers.

PMID:39023392 | DOI:10.1002/ppul.27180

Antimicrob Agents Chemother. 2024 Jul 18:e0033624. doi: 10.1128/aac.00336-24. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) airways are L-arginine deficient which may affect susceptibility to infection with certain pathogens. The potential impact of L-arginine supplementation on Pseudomonas aeruginosa, a common CF airway pathogen, is unclear. This study investigated the effects of L-arginine on P. aeruginosa biofilm cultures, using the laboratory strain PAO1 and multi-drug resistant CF clinical isolates. P. aeruginosa biofilms were grown in a chambered cover-glass slide model for 24 h, then exposed to either L-arginine alone or combined with tobramycin for an additional 24 h. Biofilms were visualized using confocal microscopy, and viable cells were measured via plating for colony-forming units. Increasing concentrations of L-arginine in bacterial culture medium reduced the biovolume of P. aeruginosa in a dose-dependent manner. Notably, L-arginine concentrations within the physiological range (50 mM and 100 mM) in combination with tobramycin promoted biofilm growth, while higher concentrations (600 mM and 1200 mM) inhibited growth. These findings demonstrate the potential of L-arginine as an adjuvant therapy to inhaled tobramycin in treating P. aeruginosa infections in people with CF.

PMID:39023260 | DOI:10.1128/aac.00336-24

Sleep Med X. 2024 May 6;7:100115. doi: 10.1016/j.sleepx.2024.100115. eCollection 2024 Dec.

ABSTRACT

Current UK guidance on OSA management recommends only selective use of sleep studies - when there is diagnostic uncertainty, in children with comorbidities or to evaluate perioperative risk in those with suspected severe OSA. Routine use of sleep studies to confirm a diagnosis of obstructive sleep apnoea (OSA) in children before adenotonsillectomy is not currently recommended. We report the findings of a novel paediatric sleep service based on routine use of multi-channel sleep studies (MCSS) before adenotonsillectomy and present the results of a service evaluation assessing the impact of our practise on treatment outcomes and cost. We conducted a retrospective study of 264 children with sleep disordered breathing seen in our centre between July 2018-June 2019, using medical records and a sleep study database to determine treatment outcomes and costs. Using responses from a questionnaire completed by otolaryngologists for a separate prospective study, we compare our costs with estimates of those associated with a standard UK model of care i.e. with selective use of sleep studies. We estimate that our routine use of MCSS reduced the number of adenotonsillectomies by 44 % but at higher monetary costs than those estimated for the standard model of care. We note however, that reconfiguring our service to arrange a sleep study before the initial appointment, rather than after, would result in the service being cost neutral compared with the standard model. We also estimate that use of home multi-channel studies in our service would bring a significant cost saving (∼£50,000 - £80,000 per annum) compared to standard care.

PMID:39022329 | PMC:PMC11252078 | DOI:10.1016/j.sleepx.2024.100115

J Food Allergy. 2024 Jul 8;2(1):124-127. doi: 10.2500/jfa.2020.2.200009. eCollection 2020 Sep.

ABSTRACT

Historically, the role of the health-care provider in medical practice has been primarily paternalistic by offering information, compassion, and decisive views with regard to medical decisions. This approach would exclude patients in the decision-making process. In a shift toward more patient-centered care, health-care providers are routinely encouraged to practice shared decision making (SDM). SDM uses evidence-based information about the options, elicitation of patient preferences, and decision support based on the patient's needs with the use of decision aids or counseling. Although there are well-known benefits of SDM, including improvements in psychological, clinical, and health-care system domains providers have found it challenging to apply SDM in everyday clinical practice. In allergy, we have a unique role in the treatment of children and adults, and SDM should be applied appropriately when engaging with these specific groups. There are many situations in which there is not a clear best option (food allergy testing, food introduction and challenges, and immunotherapy). Therefore, decision aids specific to our field, coupled with evidenced-based information that ultimately leads to a decision that reflects the patient's values will make for a vital skill in practice. In this article, we defined SDM, the benefits and barriers to SDM, unique situations in SDM, and approach to SDM in food allergy.

PMID:39022144 | PMC:PMC11250219 | DOI:10.2500/jfa.2020.2.200009

J Heart Lung Transplant. 2024 Jul 15:S1053-2498(24)01737-6. doi: 10.1016/j.healun.2024.07.003. Online ahead of print.

ABSTRACT

BACKGROUND: Primary graft dysfunction (PGD) contributes substantially to both short and long-term mortality after lung transplantation but the mechanisms that lead to PGD are not well understood. Exposure to ambient air pollutants is associated with adverse events during waitlisting for lung transplantation, and chronic lung allograft dysfunction but its association with PGD has not been studied. We hypothesized that long-term exposure of the lung donor and recipient to high levels of ambient air pollutants would increase the risk of PGD in lung transplant recipients.

METHODS: Using data from 1428 lung transplant recipients and their donors enrolled in the Lung Transplant Outcomes Group (LTOG) observational cohort study, we evaluated the association between the development of PGD and zip-code based estimates of long-term exposure to six major air pollutants (ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, PM2.5 and PM10) in both the lung donor and the lung recipient. Exposure estimates used daily EPA air pollutant monitoring data and were based on the geographic centroid of the each subject's residential zip code. Associations were tested in both univariable and multivariable models controlling for known PGD risk factors.

RESULTS: We did not find strong associations between air pollutant exposures in either the donor or the recipient and PGD.

CONCLUSIONS: Exposure to ambient air pollutants, at the levels observed in this study, may not be sufficiently harmful to prime the donor lung or the recipient to develop PGD particularly when considering the robust associations with other established PGD risk factors.

PMID:39019353 | DOI:10.1016/j.healun.2024.07.003

Cancer Epidemiol. 2024 Jul 16;92:102623. doi: 10.1016/j.canep.2024.102623. Online ahead of print.

ABSTRACT

BACKGROUND: Tobacco smoking is still frequent in Italy and a major cause of cancer globally. We estimated the burden of smoking-related cancer in Italy.

METHODS: To calculate the population attributable fraction (PAF), we adopted a counterfactual scenario for which all individuals never smoked. The PAF of current and former smoking and second-hand smoke (SHS) was estimated for cancers associated with these habits according to the International Agency for Research on Cancer. Relative risk estimates and prevalence of exposure were derived from large-scale studies and national surveys, respectively. A 20-year latency period between exposure and cancer was considered. Cancer incidence data for 2020 and mortality data for 2017 were obtained from the Italian Association of Cancer Registries.

RESULTS: Tobacco smoking caused, in men and women respectively, 90.0 % and 58.3 % of lung; 67.8 % and 53.5 % of pharyngeal; 47.0 % and 32.2 % of bladder; 45.9 % and 31.7 % of oral; 36.6 % and 23.6 % of esophageal; 23.0 % and 14.0 % of pancreatic cancer and lower percentages of cancers at other sites. Tobacco smoking accounted for 23.9 % and 7.7 % of new cancer cases in 2020, and 32.1 % and 11.3 % of cancer deaths in 2017 in men and women, respectively, corresponding to 17.3 % of cases and 24.5 % of cancer deaths overall. The PAF of lung cancer due to SHS in never smoking women married with smokers was 13.0 %.

CONCLUSIONS: Tobacco smoking is a primary cause of cancer in Italy in both sexes. Tobacco control policies are warranted.

PMID:39018889 | DOI:10.1016/j.canep.2024.102623

Sci Rep. 2024 Jul 17;14(1):16568. doi: 10.1038/s41598-024-66510-2.

ABSTRACT

Mucus stasis is a pathologic hallmark of muco-obstructive diseases, including cystic fibrosis (CF). Mucins, the principal component of mucus, are extensively modified with hydroxyl (O)-linked glycans, which are largely terminated by sialic acid. Sialic acid is a negatively charged monosaccharide and contributes to the biochemical/biophysical properties of mucins. Reports suggest that mucin sialylation may be altered in CF; however, the consequences of reduced sialylation on mucus clearance have not been fully determined. Here, we investigated the consequences of reduced sialylation on the charge state and conformation of the most prominent airway mucin, MUC5B, and defined the functional consequences of reduced sialylation on mucociliary transport (MCT). Reduced sialylation contributed to a lower charged MUC5B form and decreased polymer expansion. The inhibition of total mucin sialylation de novo impaired MCT in primary human bronchial epithelial cells and rat airways, and specific α-2,3 sialylation blockade was sufficient to recapitulate these findings. Finally, we show that ST3 beta-galactoside alpha-2,3-sialyltransferase (ST3Gal1) expression is downregulated in CF and partially restored by correcting CFTR via Elexacaftor/Tezacaftor/Ivacaftor treatment. Overall, this study demonstrates the importance of mucin sialylation in mucus clearance and identifies decreased sialylation by ST3Gal1 as a possible therapeutic target in CF and potentially other muco-obstructive diseases.

PMID:39019950 | DOI:10.1038/s41598-024-66510-2

J Cyst Fibros. 2024 Jul 16:S1569-1993(24)00791-4. doi: 10.1016/j.jcf.2024.07.006. Online ahead of print.

ABSTRACT

BACKGROUND: The 2009 cystic fibrosis (CF) infant care guidelines recommend breastmilk as the initial feeding but do not address if/when it should be fortified or supplemented with formula to promote optimal growth and pulmonary health.

METHODS: We conducted a prospective multi-center cohort study in breastfed and formula-fed infants that included 172 infants with CF who were born during 2012-17, enrolled after newborn screening at age 1.9 ± 1.0 months, and evaluated growth and lung disease manifestations in the first 3 years of life.

RESULTS: Seventy-two percent of our study cohort was breastfed at birth, but 64 % transitioned to receiving fortified feedings (breastmilk, formula, or a combination) by 6 months of age to reverse the downward trajectory of their growth curves. Fortified feedings accelerated catch-up growth to normal weight-for-age (0.12 ± 0.80 z-score) and near normal height-for-age (-0.13 ± 0.90 z-score) at 3 years of age. Within the fortified group, breastmilk and formula were similarly effective in promoting catch-up growth, but proportionately fewer infants with CF fed predominantly breastmilk (30 %) experienced severe or moderate early-onset lung disease compared to those fed predominantly formula (62 %), p = 0.02.

CONCLUSIONS: Most infants with CF require fortified feedings to recuperate from growth faltering and achieve normal growth at 3 years of age. For these infants, the proactive/preventive strategy of fortified breastmilk feedings starting soon after CF diagnosis, an alternative to the reactive/monitoring approach, can minimize the risk of prolonged postnatal growth faltering, accelerate the potential of attaining catch-up growth, and decrease the likelihood of experiencing more severe early-onset lung disease.

PMID:39019722 | DOI:10.1016/j.jcf.2024.07.006

Med Clin (Barc). 2024 Jul 16:S0025-7753(24)00390-7. doi: 10.1016/j.medcli.2024.05.014. Online ahead of print.

ABSTRACT

With the increased life expectancy of people with cystic fibrosis (CF), clinical attention has focused on prevention and treatment of non-pulmonary comorbidities. CF-related bone disease (CFBD) is a common complication and leads to increased fracture rates. Dual energy X-ray absorptiometry (DXA) is the recommended and gold standard technique to identify and monitor bone health. However, DXA has limitations because of its two-dimensional nature. Complementary tools to DXA are available, such as trabecular bone score (TBS) and vertebral fracture assessment (VFA). Quantitative computed tomography (QCT), magnetic resonance imaging (MRI) and quantitative ultrasound (QUS) may also be useful.

PMID:39019666 | DOI:10.1016/j.medcli.2024.05.014

Curr Microbiol. 2024 Jul 17;81(9):274. doi: 10.1007/s00284-024-03769-8.

ABSTRACT

Pseudomonas aeruginosa, the most prevalent opportunistic pathogen in chronic obstructive pulmonary disease, associated with high morbidity and mortality in patients with cystic fibrosis (CF), is practically impossible to be eradicated from the airways in chronicity. Its extraordinary genomic plasticity is possibly associated with high antimicrobial resistance, virulence factors, and its phenotypic diversity. The occurrence of P. aeruginosa isolates promoting airway infection, showing mucoid, non-mucoid, and small colony variant (SCV) phenotypes, was observed simultaneously, in the present study, in sputum cultures obtained from a male CF young patient with chronic pulmonary infection for over a decade. The isolates belonged to a new ST (2744) were obtained in two moments of exacerbation of the respiratory disease, in which he was hospitalized. Genetic background and phenotypic analysis indicated that the isolates exhibited multi- and pan-antimicrobial resistant profiles, as well as non-susceptible to polymyxin and predominantly hypermutable (HPM) phenotypes. Whole genome sequencing showed variations in genome sizes, coding sequences and their determinants of resistance and virulence. The annotated genomes were compared for antimicrobial resistance, hypermutability, and SCV characteristics. We highlight the lack of reported genetic determinants of SCV emergence and HPM phenotypes, which can be explained in part due to the very short time between collections of isolates. To the best of our knowledge, this is the first report of genome sequencing of P. aeruginosa SCV from a CF patient in Brazil.

PMID:39017880 | DOI:10.1007/s00284-024-03769-8

Front Immunol. 2024 Jun 28;15:1405376. doi: 10.3389/fimmu.2024.1405376. eCollection 2024.

ABSTRACT

Pseudomonas aeruginosa is a highly adaptable opportunistic pathogen capable of exploiting barriers and immune defects to cause chronic lung infections in conditions such as cystic fibrosis. In these contexts, host immune responses are ineffective at clearing persistent bacterial infection, instead driving a cycle of inflammatory lung damage. This review outlines key components of the host immune response to chronic P. aeruginosa infection within the lung, beginning with initial pathogen recognition, followed by a robust yet maladaptive innate immune response, and an ineffective adaptive immune response that propagates lung damage while permitting bacterial persistence. Untangling the interplay between host immunity and chronic P. aeruginosa infection will allow for the development and refinement of strategies to modulate immune-associated lung damage and potentiate the immune system to combat chronic infection more effectively.

PMID:39015565 | PMC:PMC11250099 | DOI:10.3389/fimmu.2024.1405376

Front Cell Infect Microbiol. 2024 Jul 2;14:1413728. doi: 10.3389/fcimb.2024.1413728. eCollection 2024.

ABSTRACT

Pseudomonas aeruginosa has already been stipulated as a "critical" pathogen, emphasizing the urgent need for researching and developing novel antibacterial agents due to multidrug resistance. Bacterial biofilm formation facilitates cystic fibrosis development and restricts the antibacterial potential of many current antibiotics. The capacity of P. aeruginosa to form biofilms and resist antibiotics is closely correlated with quorum sensing (QS). Bacterial QS is being contemplated as a promising target for developing novel antibacterial agents. QS inhibitors are a promising strategy for treating chronic infections. This study reported that the active compound PT22 (1H-pyrrole-2,5-dicarboxylic acid) isolated from Perenniporia tephropora FF2, one endophytic fungus from Areca catechu L., presents QS inhibitory activity against P. aeruginosa. Combined with gentamycin or piperacillin, PT22 functions as a novel antibiotic accelerant against P. aeruginosa. PT22 (0.50 mg/mL, 0.75 mg/mL, and 1.00 mg/mL) reduces the production of QS-related virulence factors, such as pyocyanin and rhamnolipid, and inhibits biofilm formation of P. aeruginosa PAO1 instead of affecting its growth. The architectural disruption of the biofilms was confirmed by visualization through scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Real-time quantitative PCR (RT-qPCR) indicated that PT22 significantly attenuated the expression of QS-related genes followed by docking analysis of molecules against QS activator proteins. PT22 dramatically increased the survival rate of Galleria mellonella. PT22 combined with gentamycin or piperacillin presents significant inhibition of biofilm formation and eradication of mature biofilm compared to monotherapy, which was also confirmed by visualization through SEM and CLSM. After being treated with PT22 combined with gentamycin or piperacillin, the survival rates of G. mellonella were significantly increased compared to those of monotherapy. PT22 significantly enhanced the susceptibility of gentamycin and piperacillin against P. aeruginosa PAO1. Our results suggest that PT22 from P. tephropora FF2 as a potent QS inhibitor is a candidate antibiotic accelerant to combat the antibiotic resistance of P. aeruginosa.

PMID:39015339 | PMC:PMC11250523 | DOI:10.3389/fcimb.2024.1413728