Pediatr Res. 2023 Mar 13. doi: 10.1038/s41390-023-02532-2. Online ahead of print.

ABSTRACT

BACKGROUND: Physiologic detection of bronchiolar obstruction in children with cystic fibrosis (CF) may be clinically unsuspected because of normal routine spirometry despite bronchiectasis on lung CT.

METHODS: Children from two accredited CF facilities had spirometry obtained every 3 months when clinically stable. Pre-bronchodilator maximum expiratory flow volume curves were retrospectively analyzed over 16 years to detect an isolated abnormal FEF75%, despite normal routine spirometry.

RESULTS: At Miller Children's and Women's Hospital (MCWH), an abnormal FEF75% was initially detected in 26 CF children at age 7.5 ± 4 (SD) years despite normal routine spirometry initially. FEF75% remained an isolated abnormality for 2.5 ± 1.5 years after it was initially detected in these 26 CF children. At Cohen Children's Medical Center (CCMC), despite normal routine spirometry initially, abnormal FEF75% occurred in 13 children at age 11.7 ± 4.5 years, and abnormal FEF25-75% in 10 children at age 11.8 ± 5.3 years.

CONCLUSIONS: FEF75% was most sensitive spirometric test for diagnosing both early and isolated progressive bronchiolar obstruction. Data from CCMC in older children demonstrated the simultaneous detection of abnormal FEF75% and FEF25-75% values consistent with greater bronchiolar obstruction when serial spirometry was initiated at an older age.

IMPACT: There is very little published spirometric data regarding diagnosis of isolated small airways obstruction in CF children. FEF75% can easily detect unsuspected small airways obstruction in CF children with normal routine spirometry and bronchiectasis on lung CT and optimize targeted modulatory therapies.

PMID:36914809 | DOI:10.1038/s41390-023-02532-2

J Cyst Fibros. 2023 Mar 11:S1569-1993(23)00064-4. doi: 10.1016/j.jcf.2023.02.013. Online ahead of print.

ABSTRACT

Cystic fibrosis transmembrane conductance regulator modulator therapy is associated with substantial clinical benefit and improved quality of life in patients with cystic fibrosis (CF). While their effect on lung function has been clearly reported, we are still in the process of unraveling the full impact they have on the pancreas. We present two cases of pancreatic-insufficient CF patients who presented with acute pancreatitis shortly after commencing elexacaftor/tezacaftor/ivacaftor modulator therapy. Both patients were treated with ivacaftor for 5 years prior to elexacaftor/tezacaftor/ivacaftor initiation, but had no previous episodes of acute pancreatitis. We suggest that highly effective modulator combination therapy may restore additional pancreatic acinar activity, resulting in the development of acute pancreatitis in the interim until ductal flow is improved. This report adds to the growing evidence for possible restoration of pancreatic function in patients receiving modulator therapy, and highlights that treatment with elexacaftor/tezacaftor/ivacaftor may be associated with acute pancreatitis until ductal flow is restored, even in pancreatic-insufficient CF patients.

PMID:36914434 | DOI:10.1016/j.jcf.2023.02.013

Arch Dis Child. 2023 Mar 13:archdischild-2022-324723. doi: 10.1136/archdischild-2022-324723. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the accuracy of sweat conductivity among newborns and very young infants.

DESIGN: Prospective, population-based, diagnostic test accuracy study.

SETTING: Public Statewide Newborn Screening Programme where the incidence rate of cystic fibrosis (CF) is ≈1:11 000.

PATIENTS: Newborns and very young infants with positive two-tiered immunoreactive trypsinogen.

INTERVENTIONS: Sweat conductivity and sweat chloride were performed simultaneously, on the same day and facility by independent technicians, with the cut-off values of 80 mmol/L and 60 mmol/L, respectively.

MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values (PPV and NPV), overall accuracy, positive and negative likelihood ratios (+LR, -LR) and post (sweat conductivity (SC)) test probability were calculated to assess SC performance.

RESULTS: 1193 participants were included, 68 with and 1108 without CF, and 17 with intermediate values. The mean (SD) age was 48 (19.2) days, ranging from 15 to 90 days. SC yielded sensitivity of 98.5% (95% CI 95.7 to 100), specificity of 99.9% (95% CI 99.7 to 100), PPV of 98.5% (95% CI 95.7 to 100) and NPV of 99.9% (95% CI 99.7 to 100), overall accuracy of 99.8% (95% CI 99.6 to 100), +LR of 1091.7 (95% CI 153.8 to 7744.9) and -LR of 0.01 (95% CI 0.00 to 0.10). After a positive and negative sweat conductivity result, the patient's probability of CF increases around 350 times and drops to virtually zero, respectively.

CONCLUSION: Sweat conductivity had excellent accuracy in ruling in or ruling out CF after positive two-tiered immunoreactive trypsinogen among newborns and very young infants.

PMID:36914231 | DOI:10.1136/archdischild-2022-324723

mSphere. 2023 Mar 13:e0066522. doi: 10.1128/msphere.00665-22. Online ahead of print.

ABSTRACT

Mycobacteroides abscessus is an opportunistic pathogen in people with structural lung conditions such as bronchiectasis, chronic obstructive pulmonary disease, and cystic fibrosis. Pulmonary M. abscessus infection causes progressive symptomatic and functional decline as well as diminished lung function and is often incurable with existing antibiotics. We investigated the efficacy of a new tetracycline, omadacycline, in combination with existing antibiotics recommended to treat this indication, in a mouse model of M. abscessus lung disease. Amikacin, azithromycin, bedaquiline, biapenem, cefoxitin, clofazimine, imipenem, linezolid, and rifabutin were selected as companions to omadacycline. M. abscessus burden in the lungs of mice over a 4-week treatment duration was considered the endpoint. Omadacycline in combination with linezolid, imipenem, cefoxitin, biapenem, or rifabutin exhibited early bactericidal activity compared to any single drug. Using three M. abscessus isolates, we also determined the in vitro frequency of spontaneous resistance against omadacycline to be between 1.9 × 10-10 and 6.2 × 10-10 and the frequency of persistence against omadacycline to be between 5.3 × 10-6 and 1.3 × 10-5. Based on these findings, the combination of omadacycline and select drugs that are included in the recent treatment guidelines may exhibit improved potency to treat M. abscessus lung disease. IMPORTANCE M. abscessus disease incidence is increasing in the United States. This disease is difficult to cure with existing antibiotics. In this study, we describe the efficacy of a new tetracycline antibiotic, omadacycline, in combination with an existing antibiotic to treat this disease. A mouse model of M. abscessus lung disease was used to assess the efficacies of these experimental treatment regimens. Omadacycline in combination with select existing antibiotics exhibited bactericidal activity during the early phase of treatment.

PMID:36912629 | DOI:10.1128/msphere.00665-22

Magn Reson Med. 2023 Mar 13. doi: 10.1002/mrm.29630. Online ahead of print.

ABSTRACT

PURPOSE: To explore the feasibility of measuring ventilation defect percentage (VDP) using 19 F MRI during free-breathing wash-in of fluorinated gas mixture with postacquisition denoising and to compare these results with those obtained through traditional Cartesian breath-hold acquisitions.

METHODS: Eight adults with cystic fibrosis and 5 healthy volunteers completed a single MR session on a Siemens 3T Prisma. 1 H Ultrashort-TE MRI sequences were used for registration and masking, and ventilation images with 19 F MRI were obtained while the subjects breathed a normoxic mixture of 79% perfluoropropane and 21% oxygen (O2 ). 19 F MRI was performed during breath holds and while free breathing with one overlapping spiral scan at breath hold for VDP value comparison. The 19 F spiral data were denoised using a low-rank matrix recovery approach.

RESULTS: VDP measured using 19 F VIBE and 19 F spiral images were highly correlated (r = 0.84) at 10 wash-in breaths. Second-breath VDPs were also highly correlated (r = 0.88). Denoising greatly increased SNR (pre-denoising spiral SNR, 2.46 ± 0.21; post-denoising spiral SNR, 33.91 ± 6.12; and breath-hold SNR, 17.52 ± 2.08).

CONCLUSION: Free-breathing 19 F lung MRI VDP analysis was feasible and highly correlated with breath-hold measurements. Free-breathing methods are expected to increase patient comfort and extend ventilation MRI use to patients who are unable to perform breath holds, including younger subjects and those with more severe lung disease.

PMID:36912481 | DOI:10.1002/mrm.29630

Laryngoscope. 2023 Mar 13. doi: 10.1002/lary.30642. Online ahead of print.

ABSTRACT

OBJECTIVES: Chronic rhinosinusitis (CRS) is prevalent in people with cystic fibrosis (PwCF) and is often refractory to treatments. Uncontrolled CRS might negatively impact the lower airways and the quality of life. The aim of this study is to evaluate the burden of cystic fibrosis (CF)-related CRS in the era of CF transmembrane conductance regulator (CFTR) modulators.

METHODS: Adult PwCF were asked to fill in a questionnaire on sinonasal complaints, they underwent a nasal endoscopy, bacteriological sampling, and a CT scan. Afterwards, these outcome measures were compared between patients treated with and without modulators.

RESULTS: In the 122 included patients, CRS was present in 83%. CFTR modulators were prescribed in 48% of the patients, with a median of 10 months since the start of the treatment. Subjectively, the median SNOT-22 score was 16/110. Objectively, a median Lund-Kennedy score of 6/12 and modified Lund-Mackay score of 10/24 were observed. No correlation could be found between SNOT-22 score and other outcome measures including endoscopy and radiology. Altogether, 21% of the patients had controlled disease. When comparing patients treated with and without modulators, significantly lower CT scores (p = 0.0018) and less bacterial colonization (p = 0.0082) were observed in patients receiving modulators.

CONCLUSION: CF-CRS is highly prevalent in our cohort and only the minority of PwCF has a well-controlled disease. A multidisciplinary ENT-pneumology clinic would be beneficial, as there is a high discrepancy between patient-reported symptoms and the extent of the disease. CFTR modulators are promising, as lower CT scores and less bacterial colonization were observed in the modulator group.

LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2023.

PMID:36912358 | DOI:10.1002/lary.30642

Glob Pediatr Health. 2023 Mar 6;10:2333794X221150728. doi: 10.1177/2333794X221150728. eCollection 2023.

ABSTRACT

Regular physical activity (PA) is essential in cystic fibrosis (CF). This study assessed the impact of a motivational interviewing (MI)-based project titled "Just move it . . . move it," aimed at improving the PA of pediatric CF patients. At baseline and month 6, body mass index, spirometric values, and duration of extracurricular sport activities were collected. Concurrently, the maximum oxygen uptake (VO2max) was estimated. MI was performed during each visit. Overall, 19 CF children were included. Ten patients (52.7%) increased their regular PA (mean 1.9 hours/week) between both visits (PA+ group), while 9 did not (PA- group). No significant differences in functional and nutritional values were observed between the groups, while extracurricular sport time significantly increased in the PA+ group. "Just move it . . . move it" seems to be an efficient approach, as it was able to motivate several CF patients to initiate or increase their PA, yet without improving functional parameters.

PMID:36911754 | PMC:PMC9996715 | DOI:10.1177/2333794X221150728

Front Pediatr. 2023 Feb 23;11:1111088. doi: 10.3389/fped.2023.1111088. eCollection 2023.

ABSTRACT

INTRODUCTION: Forced spirometry is the gold standard to assess lung function, but its accessibility may be limited. By contrast, home spirometry telemonitoring allows a multi-weekly lung function follow-up but its real-life adherence, reliability, and variability according to age have been poorly studied in patients with CF (PwCF). We aimed to compare real-life adherence, reliability and variability of home spirometry between children, teenagers and adults with CF.

METHODS: This real-life observational study included PwCF followed for six months in whom lung function (i.e, forced expiratory volume maximum in 1 s (FEV1), forced vital capacity (FVC), forced mid-expiratory flow (FEF) and FEV1/FVC ratio) was monitored by both conventional and home spirometry between July 2015 and December 2021. The adherence, reliability and variability of home spirometry was assessed in all PwCF and compared between children (<12years old), teenagers (12-18 years old) and adults.

RESULTS: 174 PwCF were included (74 children, 43 teenagers and 57 adults). Home spirometry was used at least one time per week by 64.1 ± 4.9% PwCF, more frequently in children and teenagers than in adults (79.4 ± 2.9%, 69.2 ± 5.5% and 40.4 ± 11.5% respectively). The reliability to conventional lung function testing was good for all assessed parameters (e.g., FEV1: r = 0.91, p < 0.01) and the variability over the 6 months of observation was low (FEV1 coefficient of variation = 11.5%). For each parameter, reliability was better, and the variability was lower in adults than in teenagers than in children.

CONCLUSION: Home spirometry telemonitoring appears to be a reliable tool for multi-weekly lung function follow-up of PwCF.

PMID:36911035 | PMC:PMC9998040 | DOI:10.3389/fped.2023.1111088

Biofilm. 2023 Mar 1;5:100111. doi: 10.1016/j.bioflm.2023.100111. eCollection 2023 Dec.

ABSTRACT

Bacterial infections of the lung frequently occur as a secondary infection to many respiratory viral infections and conditions, including influenza, COVID-19, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). Currently, clinical standard treats bacterial infections of the lung with antibiotic drugs. However, the use of broad-spectrum antibiotics can disrupt host microbiomes, lead to patient discomfort, and current clinical settings face the constantly increasing threat of drug-resistant bacteria. Biofilms further obstruct effective treatment due to their protective matrix layer, which shields bacteria from both the host immune system and antimicrobial drugs and subsequently promotes drug resistance. Alternative antimicrobial agents, including bacteriophages and antimicrobial peptides, have been utilized to treat drug-resistant bacteria. However, these antimicrobial agents have significant limitations pertaining to their ability to arrive at infection sites without compromised function and ability to persist over an extended period to fully treat infections. Enhanced delivery strategies present great promise in addressing these issues by using micro/nanoparticle carriers that shield antimicrobial agents in transit and result in sustained release, enhancing subsequent therapeutic effect and can even be modulated to be multi-functional to further improve recovery following bacterial infection.

PMID:36909663 | PMC:PMC9999167 | DOI:10.1016/j.bioflm.2023.100111

Cureus. 2023 Feb 7;15(2):e34747. doi: 10.7759/cureus.34747. eCollection 2023 Feb.

ABSTRACT

Introduction Among chronic respiratory diseases, bronchiectasis is one of the important causes of mortality and morbidity in developing countries. Objective This study aimed to assess the clinical, radiological, microbiological, and pulmonary function profiles of adult patients with post-tubercular bronchiectasis. Methods We enrolled 138 patients with bronchiectasis confirmed by high-resolution CT scans from July 2017 to August 2018. Results A total of 138 patients with bronchiectasis were enrolled. The data from 132 patients were analyzed; six patients were excluded from the study. The mean age of post-TB bronchiectasis (post-tuberculosis bronchiectasis) patients was 36.08±13.08, which was lower than the non-tuberculosis bronchiectasis group. The proportion of the male population was more in the post-TB bronchiectasis group (54.55% vs. 37.88%, p=0.48). Smoking prevalence was high in post-TB bronchiectasis (27.27% vs. 12.12%, p=0.04). The predominant symptom was cough in the post-tubercular bronchiectasis group (48.5% vs. 41.7%, p=0.019). The history of the recurrent common cold was seen most frequently in non-post-tubercular bronchiectasis (40.9% vs. 12.9%, p=0.001). The most common radiological variant of bronchiectasis found in all patients was a cystic type (75%). The most common site of involvement was the left lower lobe, followed by the lingula in all patients and post-tuberculosis bronchiectasis patients. Pulmonary function on spirometry revealed obstructive, restrictive, and mixed patterns in 55%, 25%, and 15%, respectively. Patients with post-tuberculosis bronchiectasis had lower lung function post-FEV1/FVC (forced expiratory volume in one second/forced vital capacity) ratio (70.31±15.56 vs. 76.85±11.82, p=0.015). Binary multivariate logistic regression analysis showed that only recurrent cough cold was a significant independent risk factor for post-TB bronchiectasis. Conclusion Post-tuberculosis, and bronchiectasis followed by post-infectious causes, were the most common causes of bronchiectasis and poor lung function.

PMID:36909094 | PMC:PMC9998134 | DOI:10.7759/cureus.34747

Arch Gynecol Obstet. 2023 Mar 13. doi: 10.1007/s00404-023-06962-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Management of cystic fibrosis has recently stepped forward with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, although data on potential adverse effects are lacking for many categories of patients, such as pregnant women.

METHODS: We report one of the first reports on the outcome of pregnancy in a woman treated with Elexacaftor/Tezacaftor/Ivacaftor during the second and third trimester of pregnancy, showing a significant improvement of respiratory status, compared with the first trimester when the medication was discontinued due to unknown and, therefore, potential teratogenic effects. Also, we performed the review of the existing literature on the topic.

RESULTS: The course of pregnancy was uneventful, with reference to major obstetric complications, and the patient delivered a healthy neonate. These results were similar to those coming from other short series of pregnant women affected by cystic fibrosis and treated with CFTR modulators during pregnancy.

CONCLUSIONS: Thus, despite the lack of evidence on the topic, the use of Elexacaftor/Tezacaftor/Ivacaftor in pregnancy seems to be apparently not associated with major adverse events, thus opening optimistic scenarios in terms of management of these patients.

PMID:36907900 | DOI:10.1007/s00404-023-06962-5

J Cyst Fibros. 2023 Jan;22(1):7-8. doi: 10.1016/j.jcf.2023.01.009.

NO ABSTRACT

PMID:36907644 | DOI:10.1016/j.jcf.2023.01.009

J Cyst Fibros. 2023 Jan;22(1):3-4. doi: 10.1016/j.jcf.2023.01.016.

NO ABSTRACT

PMID:36907643 | DOI:10.1016/j.jcf.2023.01.016

Cells. 2023 Mar 4;12(5):806. doi: 10.3390/cells12050806.

ABSTRACT

The identification of Parkinson's disease (PD) biomarkers has become a main goal for the diagnosis of this neurodegenerative disorder. PD has not only been intrinsically related to neurological problems, but also to a series of alterations in peripheral metabolism. The purpose of this study was to identify metabolic changes in the liver in mouse models of PD with the scope of finding new peripheral biomarkers for PD diagnosis. To achieve this goal, we used mass spectrometry technology to determine the complete metabolomic profile of liver and striatal tissue samples from WT mice, 6-hydroxydopamine-treated mice (idiopathic model) and mice affected by the G2019S-LRRK2 mutation in LRRK2/PARK8 gene (genetic model). This analysis revealed that the metabolism of carbohydrates, nucleotides and nucleosides was similarly altered in the liver from the two PD mouse models. However, long-chain fatty acids, phosphatidylcholine and other related lipid metabolites were only altered in hepatocytes from G2019S-LRRK2 mice. In summary, these results reveal specific differences, mainly in lipid metabolism, between idiopathic and genetic PD models in peripheral tissues and open up new possibilities to better understand the etiology of this neurological disorder.

PMID:36899942 | PMC:PMC10000529 | DOI:10.3390/cells12050806

BDJ Open. 2023 Mar 11;9(1):11. doi: 10.1038/s41405-023-00136-w.

ABSTRACT

OBJECTIVES: To investigate the attitudes of adults with Cystic Fibrosis (CF) towards dental attendance and any perceived barriers to treatment.

METHODS: A cross sectional survey in the form of a structured, anonymous questionnaire was used to obtain information regarding adults with CF's feelings towards dentists and dental treatment. The final version of the questionnaire was based on a collaborative effort between researchers at Cork University Dental School and Hospital and Cystic Fibrosis (CF) patient advocates from CF Ireland. Participants were recruited via CF Ireland's mailing list and social media channels. The responses underwent descriptive statistical analysis and inductive thematic analysis.

RESULTS: A total of 71 people (33 Male: 38 Female) over the age of 18 living with CF in the Republic of Ireland responded to the survey. 54.9% of respondents were unhappy with their teeth. 63.4% felt that CF had an impact on oral health. 33.8% were anxious about attending their dentist. Respondents believed that CF has impacted on their oral health due to the medications and dietary requirements involved, as well as tiredness and other side effects of CF. Reasons for being anxious about attending the dentist included cross infection concerns, issues with the dentist, with tolerating treatment, and with the teeth themselves. Respondents wanted dentists to be aware of the practicalities of dental treatment for people with CF, especially their discomfort with lying back. They also want the dentist to be aware of the impact that their medication, treatment and diet has on their oral health.

CONCLUSIONS: Over one third of adults with CF reported anxiety about attending the dentist. Reasons for this included fear, embarrassment, cross infection concerns and problems with treatment, especially being in the supine position. Adults with CF want dentists to be aware of the impact that CF can have upon dental treatment and oral health care.

PMID:36906647 | DOI:10.1038/s41405-023-00136-w

J Cyst Fibros. 2023 Mar 6:S1569-1993(23)00065-6. doi: 10.1016/j.jcf.2023.03.001. Online ahead of print.

NO ABSTRACT

PMID:36906393 | DOI:10.1016/j.jcf.2023.03.001

Sensors (Basel). 2023 Feb 23;23(5):2491. doi: 10.3390/s23052491.

ABSTRACT

The ion-sensitive field-effect transistor is a well-established electronic device typically used for pH sensing. The usability of the device for detecting other biomarkers in easily accessible biologic fluids, with dynamic range and resolution compliant with high-impact medical applications, is still an open research topic. Here, we report on an ion-sensitive field-effect transistor that is able to detect the presence of chloride ions in sweat with a limit-of-detection of 0.004 mol/m3. The device is intended for supporting the diagnosis of cystic fibrosis, and it has been designed considering two adjacent domains, namely the semiconductor and the electrolyte containing the ions of interest, by using the finite element method, which models the experimental reality with great accuracy. According to the literature explaining the chemical reactions that take place between the gate oxide and the electrolytic solution, we have concluded that anions directly interact with the hydroxyl surface groups and replace protons previously adsorbed from the surface. The achieved results confirm that such a device can be used to replace the traditional sweat test in the diagnosis and management of cystic fibrosis. In fact, the reported technology is easy-to-use, cost-effective, and non-invasive, leading to earlier and more accurate diagnoses.

PMID:36904697 | DOI:10.3390/s23052491

J Clin Med. 2023 Feb 21;12(5):1730. doi: 10.3390/jcm12051730.

ABSTRACT

Patients with cystic fibrosis often complain of joint manifestations. However, only a few studies have reported the association between cystic fibrosis and juvenile idiopathic arthritis and addressed the therapeutic challenges of these patients. We describe the first paediatric case of a patient affected by cystic fibrosis, Basedow's disease and juvenile idiopathic arthritis who was contemporarily treated with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) and anti-tumor necrosis factor α (anti-TNFα). This report seems to reassure regarding the potential side effects of these associations. Moreover, our experience suggests that anti-TNFα is an effective option in CF patients affected by juvenile idiopathic arthritis, and is even safe for children receiving a triple CFTR modulator.

PMID:36902517 | DOI:10.3390/jcm12051730

Int J Mol Sci. 2023 Mar 6;24(5):5034. doi: 10.3390/ijms24055034.

ABSTRACT

Neutrophils are important effector cells of the innate immune response that fight pathogens by phagocytosis and degranulation. Neutrophil extracellular traps (NETs) are released into the extracellular space to defend against invading pathogens. Although NETs play a defensive role against pathogens, excessive NETs can contribute to the pathogenesis of airway diseases. NETs are known to be directly cytotoxic to the lung epithelium and endothelium, highly involved in acute lung injury, and implicated in disease severity and exacerbation. This review describes the role of NET formation in airway diseases, including chronic rhinosinusitis, and suggests that targeting NETs could be a therapeutic strategy for airway diseases.

PMID:36902466 | DOI:10.3390/ijms24055034

Int J Mol Sci. 2023 Mar 5;24(5):5010. doi: 10.3390/ijms24055010.

ABSTRACT

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, a new series of therapeutics that correct and potentiate some classes of mutations of the CFTR, have provided a great therapeutic advantage to people with cystic fibrosis (pwCF). The main hindrances of the present CFTR modulators are related to their limitations in reducing chronic lung bacterial infection and inflammation, the main causes of pulmonary tissue damage and progressive respiratory insufficiency, particularly in adults with CF. Here, the most debated issues of the pulmonary bacterial infection and inflammatory processes in pwCF are revisited. Special attention is given to the mechanisms favoring the bacterial infection of pwCF, the progressive adaptation of Pseudomonas aeruginosa and its interplay with Staphylococcus aureus, the cross-talk among bacteria, the bronchial epithelial cells and the phagocytes of the host immune defenses. The most recent findings of the effect of CFTR modulators on bacterial infection and the inflammatory process are also presented to provide critical hints towards the identification of relevant therapeutic targets to overcome the respiratory pathology of pwCF.

PMID:36902441 | DOI:10.3390/ijms24055010