Pediatr Pulmonol. 2022 Mar 5. doi: 10.1002/ppul.25883. Online ahead of print.

ABSTRACT

In response to the letter by Grant and colleagues highlighting the impact and need for pharmacy services in patients with cystic fibrosis, we also wish to highlight the unique need for a pharmacist as an essential member of the team caring for patients with childhood interstitial lung disease (chILD). This article is protected by copyright. All rights reserved.

PMID:35246971 | DOI:10.1002/ppul.25883

Pediatr Res. 2022 Mar 4. doi: 10.1038/s41390-022-01986-0. Online ahead of print.

ABSTRACT

BACKGROUND: Kaposiform lymphangiomatosis (KLA) is a complex lymphatic anomaly involving most commonly the mediastinum, lung, skin and bones with few effective treatments. In recent years, RAS-MAPK pathway mutations were shown to underlie the pathogenesis of several complex lymphatic anomalies. Specifically, an activating NRAS mutation (p.Q61R) was found in the majority of KLA patients. Recent reports demonstrated promising results of treatment with the MEK inhibitor, Trametinib, in patients with complex lymphatic anomalies harboring gain of function mutations in ARAF and SOS1, as well as loss of function mutation in the CBL gene, a negative regulator of the RAS-MAPK pathway. We present a 9-year-old child with a severe case of KLA harboring the typical NRAS (p.Q61R) mutation detected by plasma-derived cell free DNA, responsive to trametinib therapy.

METHODS: The NRAS somatic mutation was detected from plasma cfDNA using droplet digital PCR. Concurrent in-vitro studies of trametinib activity on mutant NRAS affected lymphatic endothelial cells were performed using a three-dimensional spheroid sprouting assay.

RESULTS: Trametinib treatment lead to resolution of lifelong thrombocytopenia, improvement of pulmonary function tests and wellbeing, as well as weaning from prolonged systemic steroid treatment. Concurrent studies of mutant NRAS-expressing cells showed enhanced lymphangiogenic capacity along with over activation of the RAS-MAPK and PI3K-AKT-mTOR pathways, both reversed by trametinib.

CONCLUSIONS: Trametinib treatment can substantially change the prognosis of patients with RAS pathway associated lymphatic anomalies.

IMPACT: This is the first description of successful trametinib treatment of a patient with KLA harboring the most characteristic NRAS p.Q61R mutation. Treatment can significantly change the prognosis of patients with RAS pathway-associated lymphatic anomalies. We devised an in vitro model of KLA enabling a reproducible method for the continued study of disease pathogenesis. Mutated NRAS p.Q61R cells demonstrated increased lymphangiogenic capacity.

PMID:35246606 | DOI:10.1038/s41390-022-01986-0

J Cyst Fibros. 2022 Mar 1:S1569-1993(22)00048-0. doi: 10.1016/j.jcf.2022.02.016. Online ahead of print.

ABSTRACT

In cystic fibrosis (CF) patients, Ear Nose Throat (ENT) pathology is often undiagnosed despite its high prevalence and its possible life-threatening complications. We present the case of an ethmoidal mucocele leading to ocular manifestations in a 2-year-old girl with cystic fibrosis with no previous serious complications. She progressively developed non-axial proptosis, limitation of the adduction and exotropia of her left eye. Paranasal sinus magnetic resonance image (MRI) showed a left ethmoidal mucocele causing displacement of the ocular globe, compression of the medial rectus and the optic nerve. Eye fundus revealed disc edema and diffuse vascular congestion. Endoscopic sinus surgery was performed to remove the mass. The mucocele was drained and the discharge was sent for microbiology assessment. Escherichia coli (E. coli) was found in the culture and treated with cefotaxime and dexamethasone with complete resolution of non-axial proptosis and disc edema.

PMID:35246383 | DOI:10.1016/j.jcf.2022.02.016

J Magn Reson Imaging. 2022 Mar 4. doi: 10.1002/jmri.28136. Online ahead of print.

ABSTRACT

BACKGROUND: 129 Xe gas-transfer MRI provides regional measures of pulmonary gas exchange in adults and separates xenon in interstitial lung tissue/plasma (barrier) from xenon in red blood cells (RBCs). The technique has yet to be demonstrated in pediatric populations or conditions.

PURPOSE/HYPOTHESIS: To perform an exploratory analysis of 129 Xe gas-transfer MRI in children.

STUDY TYPE: Prospective.

POPULATION: Seventy-seven human volunteers (38 males, age = 17.7 ± 15.1 years, range 5-68 years, 16 healthy). Four pediatric disease cohorts.

FIELD STRENGTH/SEQUENCE: 3-T, three-dimensional-radial one-point Dixon Fast Field Echo (FFE) Ultrashort Echo Time (UTE).

ASSESSMENT: Breath hold compliance was assessed by quantitative signal-to-noise and dynamic metrics. Whole-lung means and standard deviations were extracted from gas-transfer maps. Gas-transfer metrics were investigated with respect to age and lung disease. Clinical pulmonary function tests were retrospectively acquired for reference lung disease severity.

STATISTICAL TESTS: Wilcoxon rank-sum tests to compare age and disease cohorts, Wilcoxon signed-rank tests to compare pre- and post-breath hold vitals, Pearson correlations between age and gas-transfer metrics, and limits of normal with a binomial exact test to compare fraction of subjects with abnormal gas-transfer. P ≤ 0.05 was considered significant.

RESULTS: Eighty percentage of pediatric subjects successfully completed 129 Xe gas-transfer MRI. Gas-transfer parameters differed between healthy children and adults, including ventilation (0.75 and 0.67) and RBC:barrier ratio (0.31 and 0.46) which also correlated with age (ρ = -0.76, 0.57, respectively). Bone marrow transplant subjects had impaired ventilation (90% of reference) and increased dissolved 129 Xe standard deviation (242%). Bronchopulmonary dysplasia subjects had decreased barrier-uptake (69%). Cystic fibrosis subjects had impaired ventilation (91%) and increased RBC-transfer (146%). Lastly, childhood interstitial lung disease subjects had increased ventilation heterogeneity (113%). Limits of normal provided detection of abnormalities in additional gas-transfer parameters.

DATA CONCLUSION: Pediatric 129 Xe gas-transfer MRI was adequately successful and gas-transfer metrics correlated with age. Exploratory analysis revealed abnormalities in a variety of pediatric obstructive and restrictive lung diseases.

LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

PMID:35244302 | DOI:10.1002/jmri.28136

Clin Transplant. 2022 Mar 4:e14634. doi: 10.1111/ctr.14634. Online ahead of print.

ABSTRACT

There has been a shift over decades in the diagnostic indications for lung transplantation in children; in particular, there has been a reduction in the proportion of pediatric cystic fibrosis (CF) patients undergoing lung transplantation early in life, and more transplants occurring in other diagnostic groups. Here, we examine trends in pediatric lung transplantation with regards to indication by analyzing data from the United Network of Organ Sharing, the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, and other sources. Over the past two years, there has been a precipitous decline in both the number of transplants due to CF and the proportion of CF cases relative to the total number of transplants, likely not solely due to the COVID-19 pandemic. In 2020, primary pulmonary arterial hypertension for the first time surpassed CF as main indication for pediatric lung transplantation in the United States, a finding that is also reflected in international data. We discuss the effect of novel CFTR modulator therapies as a major factor leading to this shifting landscape. Based on our trending, pulmonary hypertension-related diagnoses and pediatric interstitial lung diseases are rising indications, for which we suggest adjustments of consensus guidelines around candidate selection criteria. This article is protected by copyright. All rights reserved.

PMID:35244236 | DOI:10.1111/ctr.14634

Pediatr Pulmonol. 2022 Mar 3. doi: 10.1002/ppul.25882. Online ahead of print.

ABSTRACT

BACKGROUND: The largest age group among children and adolescents referred for lung transplantation for cystic fibrosis (CF) have been those in the pubertal or post pubertal age range. However, over 100 younger patients with CF have undergone lung transplantation over the last three decades in the USA.

METHODS: We performed a retrospective review of our experience with 18 children with CF who underwent lung transplantation in our center before the age of 11 years and compared them to our older CF lung transplant recipients and our larger CF Center population.

RESULTS: The transplant population was demographically distinct from our CF center in terms of ethnicity, country of origin, and insurance status. Other notable findings were a high prevalence of methicillin-resistant Staphylococcus aureus, a high prevalence of CF-related diabetes mellitus and a high prevalence of consolidated lobar or whole lung disease. Post-transplant outcomes were comparable to those older than 10 years of age in our center until five years after transplant after which the younger cohort showed a superior enduring survival.

CONCLUSIONS: In an era of increasingly effective medications modifying the natural history of CF, identification of risk factors for early severe lung disease in CF remains relevant to permit interventions to prevent or postpone the time of future lung transplantation. This article is protected by copyright. All rights reserved.

PMID:35243829 | DOI:10.1002/ppul.25882

Cureus. 2022 Jan 29;14(1):e21711. doi: 10.7759/cureus.21711. eCollection 2022 Jan.

ABSTRACT

Achromobacter xylosoxidans is an aerobic, Gram-negative rod with a broad intrinsic and acquired antimicrobial resistance, usually isolated in patients with cystic fibrosis (CF), immunodeficiencies, or those undergoing invasive procedures. We report a case of a previously healthy 14-year-old girl who was hospitalized in our institution due to a prolonged, progressive cough and exertional dyspnea, which started after a mild viral respiratory tract infection. To elucidate the cause of her symptoms, a bronchoscopy was finally performed, showing bilateral purulent bronchitis caused by A. xylosoxidans, isolated from bronchoalveolar lavage (BAL) sample. Since the patient had positive serological testing for coronavirus disease 2019 (COVID-19), we concluded that it was the initial viral infection, although of a mild clinical course, the one that created favorable conditions for proliferation and further inflammation caused by A. xylosoxidans.

PMID:35242477 | PMC:PMC8884523 | DOI:10.7759/cureus.21711

J Micromech Microeng. 2021 Dec;31(12):125006. doi: 10.1088/1361-6439/ac2d9c. Epub 2021 Oct 26.

ABSTRACT

BACKGROUND AND AIMS: The role of the crypt microarchitecture and surrounding tissue curvature on intestinal stem/proliferative cell physiology is unknown. The utility of liquid lithography in creating polydimethylsiloxane (PDMS) micropillar stamps with controlled tip curvature was assessed. Using these stamps, the impact of microcurvature at the crypt base on intestinal cell and cytoskeletal behavior was studied.

METHODS: An SU-8 master mold as a support, polyols of varying surface energies as sacrificial liquids, and liquid PDMS as the solidifiable material were combined using liquid lithography to form PDMS micropillar arrays. Vapor phase deposition of organosilane onto the master mold was used to modify the surface energy of the master mold to shape the micropillar tips. Collagen was molded using the micropillar arrays forming a scaffold for culture of human primary colonic epithelial cells. Cell proliferation and cytoskeletal properties were assessed using fluorescent stains.

RESULTS: Liquid lithography using low surface energy polyols (<55 dynes/cm) generated convex-tipped PDMS micropillars, while polyols with higher surface energies (>55 dynes/cm) yielded concave-tipped PDMS micropillars. Gradients of octyltrichlorosilane deposition across a master mold with an array of microwells yielded a PDMS micropillar array with a range of tip curvatures. Human primary colonic epithelial cells cultured on micropillar-molded collagen scaffolds demonstrated a stem/proliferative cell compartment at the crypt base. Crypts with a convex base demonstrated significantly lower cell proliferation at the crypt base than that of cells in crypts with either flat or concave bases. Crypts with a convex base also displayed higher levels of G-actin activity compared to that of crypts with flat or concave bases.

CONCLUSIONS: Liquid lithography enabled creation of arrays of in vitro colonic crypts with programmable curvature. Primary cells at the crypt base sensed and responded to surface curvature by altering their proliferation and cytoskeletal properties.

PMID:35241878 | PMC:PMC8887876 | DOI:10.1088/1361-6439/ac2d9c

Acta Pharmacol Sin. 2022 Mar 3. doi: 10.1038/s41401-022-00868-9. Online ahead of print.

ABSTRACT

Platelet hyperactivity is essential for thrombus formation in coronary artery diseases (CAD). Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients with cystic fibrosis elevates intracellular Cl- levels ([Cl-]i) and enhanced platelet hyperactivity. In this study, we explored whether alteration of [Cl-]i has a pathological role in regulating platelet hyperactivity and arterial thrombosis formation. CFTR expression was significantly decreased, while [Cl-]i was increased in platelets from CAD patients. In a FeCl3-induced mouse mesenteric arteriole thrombosis model, platelet-specific Cftr-knockout and/or pre-administration of ion channel inhibitor CFTRinh-172 increased platelet [Cl-]i, which accelerated thrombus formation, enhanced platelet aggregation and ATP release, and increased P2Y12 and PAR4 expression in platelets. Conversely, Cftr-overexpressing platelets resulted in subnormal [Cl-]i, thereby decreasing thrombosis formation. Our results showed that clamping [Cl-]i at high levels or Cftr deficiency-induced [Cl-]i increasement dramatically augmented phosphorylation (Ser422) of serum and glucocorticoid-regulated kinase (SGK1), subsequently upregulated P2Y12 and PAR4 expression via NF-κB signaling. Constitutively active mutant S422D SGK1 markedly increased P2Y12 and PAR4 expression. The specific SGK1 inhibitor GSK-650394 decreased platelet aggregation in wildtype and platelet-specific Cftr knockout mice, and platelet SGK1 phosphorylation was observed in line with increased [Cl-]i and decreased CFTR expression in CAD patients. Co-transfection of S422D SGK1 and adenovirus-induced CFTR overexpression in MEG-01 cells restored platelet activation signaling cascade. Our results suggest that [Cl-]i is a novel positive regulator of platelet activation and arterial thrombus formation via the activation of a [Cl-]i-sensitive SGK1 signaling pathway. Therefore, [Cl-]i in platelets is a novel potential biomarker for platelet hyperactivity, and CFTR may be a potential therapeutic target for platelet activation in CAD.

PMID:35241769 | DOI:10.1038/s41401-022-00868-9

Paediatr Respir Rev. 2022 Feb 12:S1526-0542(22)00010-0. doi: 10.1016/j.prrv.2022.02.001. Online ahead of print.

ABSTRACT

The looming antibiotic resistance crisis is forcing clinicians to consider alternative approaches to treating bacterial infections. As the window of use for current antimicrobial agents becomes ever narrower, we consider if looking back will now be the way forward. Conceptually, phage therapy is simple and specific; a targeted treatment to control bacterial overgrowth. In this article we discuss bacteriophage and potential use in future therapy.

PMID:35241371 | DOI:10.1016/j.prrv.2022.02.001

World Rev Nutr Diet. 2022;124:374-381. doi: 10.1159/000517004. Epub 2022 Mar 3.

NO ABSTRACT

PMID:35240644 | DOI:10.1159/000517004

Microb Pathog. 2022 Feb 28:105461. doi: 10.1016/j.micpath.2022.105461. Online ahead of print.

ABSTRACT

OBJECTIVE: Pseudomonas aeruginosa is an opportunistic pathogen that infects the lungs of people with cystic fibrosis (CF) and is the most common cause of chronic respiratory infections with high morbidity and mortality in CF patients. This study aimed to evaluate the pattern of antibiotic resistance of P. aeruginosa strains from patients with CF using a systematic review and meta-analysis.

METHODS: A comprehensive and systematic search was performed for relevant articles until August 2021 in the following database: PubMed, Scopus, Embase, and Web of Science. Finally, 122 articles with appropriate criteria were included in the meta-analysis. To estimate weighted pooled proportions Freeman-Tukey double arcsine transformation was performed using Metaprop command in Stata software version 17.1.

RESULTS: 122 studies evaluated the pattern of P. aeruginosa antibiotic resistance from different antibiotic classes in patients with CF. Cefotaxime had the highest resistance rate of 67% (95% CI 53_80%), while colistin had the lowest 5% (95% CI 2-8%).

CONCLUSION: High resistance to most of the studied antibiotics was observed. The high antibiotic resistance observed is worrying and it indicates the need to monitor using of antibiotics. In addition, colistin is the most appropriate treatment choice, but more randomized controlled trial studies are recommended.

PMID:35240288 | DOI:10.1016/j.micpath.2022.105461

BMJ Case Rep. 2022 Mar 2;15(3):e247042. doi: 10.1136/bcr-2021-247042.

ABSTRACT

We present a case of severe rash following induction of elexacaftor, tezacaftor and ivacaftor (ELX/TEZ/IVA) in a young adult male cystic fibrosis patient. While rash is a commonly reported side effect which resolves in 1-2 weeks with minimal intervention, our patient had presented with fever and widespread rash prompting medication cessation. After a washout period, reintroduction with 1/2 tablet of ELX/TEZ/IVA produced a similar systemic response within 24 hours. Repeat attempt, this time with 1/8 tablet and increasing in increments of an eighth daily, was successful and has allowed our patient to experience the transformative benefits of ELX/TEZ/IVA including improved pulmonary function and reduced episodes of infective exacerbation. This case illustrates one of the most common side effects of ELX/TEZ/IVA triple therapy, and our experience of desensitisation to ELX/TEZ/IVA in a challenging case of rash.

PMID:35236685 | DOI:10.1136/bcr-2021-247042

Clin Chest Med. 2022 Mar;43(1):99-125. doi: 10.1016/j.ccm.2021.12.002.

ABSTRACT

Allergic bronchopulmonary aspergillosis (ABPA) is a complex allergic disorder caused by immune reactions against Aspergillus fumigatus. ABPA most commonly complicates the course of patients with poorly controlled asthma. Patients commonly present with uncontrolled asthma, fleeting pulmonary opacities, and bronchiectasis. Pathogenetically, ABPA is characterized by the persistence of A. fumigatus in the airways and an exaggerated type-2 immune response. The interest in ABPA stems from the fact that bronchiectasis in ABPA can be prevented if the disorder is diagnosed timely and treated appropriately. Herein, we summarize the current concepts in the epidemiology, pathogenesis, diagnosis, and treatment of ABPA.

PMID:35236565 | DOI:10.1016/j.ccm.2021.12.002

Clin Chest Med. 2022 Mar;43(1):47-60. doi: 10.1016/j.ccm.2021.11.004.

ABSTRACT

Bronchiectasis is a radiological diagnosis made using computed tomographic (CT) imaging. Although visual CT assessment is necessary for the diagnosis of bronchiectasis, visual assessment of disease severity and progression is challenging. Computer tools offer the potential to improve the characterization of lung damage in patients with bronchiectasis. Newer imaging techniques such as MRI with hyperpolarized gas inhalation have the potential to identify early forms of disease and are without the constraints of requiring ionizing radiation exposure.

PMID:35236560 | DOI:10.1016/j.ccm.2021.11.004

Heart Lung. 2022 Feb 27;53:89-98. doi: 10.1016/j.hrtlng.2022.02.006. Online ahead of print.

ABSTRACT

BACKGROUND: Active cycle breathing technique (ACBT), which includes cycle of breathing control, thoracic expansion exercises and forced expiratory technique (FET), appears to have beneficial effects in patients with a variety of respiratory diseases. This systematic review provides an update on the new related studies, expanding the evidence base through the last 12 years and specifically evaluating the effectiveness of ACBT on pulmonary function-related outcome variables in patients with chronic respiratory diseases.

METHODS: MEDLINE/Pubmed, PEDro, and Cochrane Library for Randomized Controlled Trials were searched between September 2008 and December 2021, in continuance of a previous systematic review, to identify randomized clinical trials and/or crossover studies comparing ACBT to other respiratory treatment techniques in patients with chronic obstructive pulmonary diseases, cystic fibrosis, or bronchiectasis.

RESULTS: Eleven studies were included and the quality of most of them was moderate to good. The outcomes most frequently assessed were forced expiratory volume in 1 s (FEV1), sputum wet weight, forced vital capacity (FVC), and peak expiratory flow rate. Secondary outcomes were quality of life and dyspnea. Various comparators were identified and most of them assessed the ACBT as an effective method in comparison with other respiratory treatment modalities. Most studies revealed that ACBT/FET had at least an equally beneficial short-term effect on sputum wet weight, FEV1 and FVC compared to other treatment methods.

CONCLUSION: The results of this updating review reinforced the data of a previous systematic review regarding the beneficial impact of ACBT for the short-term improvement in respiratory tract secretions clearance and pulmonary function. ACBT is effective in increasing the expectorated sputum volume, in reducing viscoelasticity of the secretion and in relieving symptoms such as dyspnea.

PMID:35235877 | DOI:10.1016/j.hrtlng.2022.02.006

Am J Respir Cell Mol Biol. 2022 Mar 2. doi: 10.1165/rcmb.2021-0499OC. Online ahead of print.

ABSTRACT

Lack of CFTR affects the transcriptome, composition, and function of large and small airway epithelia in people with advanced cystic fibrosis (CF); however, whether lack of CFTR causes cell-intrinsic abnormalities present at birth vs. inflammation-dependent abnormalities is unclear. We performed a single cell RNA-seq census of micro-dissected small airways from newborn CF pigs, which recapitulate CF host defense defects and pathology over time. Lack of CFTR minimally affected the transcriptome of large and small airways at birth, suggesting that infection and inflammation drive transcriptomic abnormalities in advanced CF. Importantly, common small airway epithelial cell types expressed a markedly different transcriptome than corresponding large airway cell types. Quantitative immunohistochemistry and electrophysiology of small airway epithelia demonstrated basal cells that reach the apical surface and a water and ion transport advantage. This single cell atlas highlights the archetypal nature of airway epithelial cells with location-dependent gene expression and function.

PMID:35235762 | DOI:10.1165/rcmb.2021-0499OC

Braz J Microbiol. 2022 Mar 2. doi: 10.1007/s42770-022-00707-3. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is a gram-negative bacterium capable of forming persistent biofilms that are extremely difficult to eradicate. The species is most infamously known due to complications in cystic fibrosis patients. The high mortality of cystic fibrosis is caused by P. aeruginosa biofilms occurring in pathologically overly mucous lungs, which are the major cause facilitating the organ failure. Due to Pseudomonas biofilm-associated infections, remarkably high doses of antibiotics must be administered, eventually contributing to the development of antibiotic resistance. Nowadays, multidrug resistant P. aeruginosa is one of the most terrible threats in medicine, and the search for novel antimicrobial drugs is of the utmost importance. We have studied the effect of low molecular weight chitosan (LMWCH) on various stages of P. aeruginosa ATCC 10145 biofilm formation and eradication, as well as on production of other virulence factors. LMWCH is a well-known naturally occurring agent with a vast antimicrobial spectrum, which has already found application in various fields of medicine and industry. LMWCH at a concentration of 40 mg/L was able to completely prevent biofilm formation. At a concentration of 60 mg/L, this agent was capable to eradicate already formed biofilm in most studied times of addition (2-12 h of cultivation). LMWCH (50 mg/L) was also able to suppress pyocyanin production when added 2 and 4 h after cultivation. The treatment resulted in reduced formation of cell clusters. LMWCH was proved to be an effective antibiofilm agent worth further clinical research with the potential to become a novel drug for the treatment of P. aeruginosa infections.

PMID:35235193 | DOI:10.1007/s42770-022-00707-3

Nucleic Acids Res. 2022 Mar 2:gkac137. doi: 10.1093/nar/gkac137. Online ahead of print.

ABSTRACT

Burkholderia cenocepacia is an opportunistic pathogen that causes severe infections of the cystic fibrosis (CF) lung. To acquire iron, B. cenocepacia secretes the Fe(III)-binding compound, ornibactin. Genes for synthesis and utilisation of ornibactin are served by the iron starvation (IS) extracytoplasmic function (ECF) σ factor, OrbS. Transcription of orbS is regulated in response to the prevailing iron concentration by the ferric uptake regulator (Fur), such that orbS expression is repressed under iron-sufficient conditions. Here we show that, in addition to Fur-mediated regulation of orbS, the OrbS protein itself responds to intracellular iron availability. Substitution of cysteine residues in the C-terminal region of OrbS diminished the ability to respond to Fe(II) in vivo. Accordingly, whilst Fe(II) impaired transcription from and recognition of OrbS-dependent promoters in vitro by inhibiting the binding of OrbS to core RNA polymerase (RNAP), the cysteine-substituted OrbS variant was less responsive to Fe(II). Thus, the cysteine residues within the C-terminal region of OrbS contribute to an iron-sensing motif that serves as an on-board 'anti-σ factor' in the presence of Fe(II). A model to account for the presence two regulators (Fur and OrbS) that respond to the same intracellular Fe(II) signal to control ornibactin synthesis and utilisation is discussed.

PMID:35234897 | DOI:10.1093/nar/gkac137

J Cyst Fibros. 2022 Feb 26:S1569-1993(22)00045-5. doi: 10.1016/j.jcf.2022.02.013. Online ahead of print.

NO ABSTRACT

PMID:35232654 | DOI:10.1016/j.jcf.2022.02.013