Front Endocrinol (Lausanne). 2022 Feb 21;13:773753. doi: 10.3389/fendo.2022.773753. eCollection 2022.

ABSTRACT

RESEARCH QUESTION: Unlike in men, a very limited number of studies were focused on the specificity of ART management of cystic fibrosis (CF) in women. The purpose of this study was to determine the causes of infertility in patients, the appropriate ART treatment, and their prognosis in terms of pregnancy.

DESIGN: We conducted a multicentre analytical case-control study including CF women who were age-matched to non-CF women. We reported the causes of infertility, the ART management type and pregnancy outcomes.

RESULTS: 17 cases were compared to 34 controls. There was no significant difference between the groups concerning cause infertility. There was a non-statistically significant trend with a lower antral follicle count in CF compared to controls (19.5 versus 26.8, p=0.08). IUI seemed to be as successful as IVF/ICSI in CF as opposed to controls where the IVF/ICSI was the most effective (in CF group for HCG >100 UI/L: 38.8% vs. 36.8%, p=0.4175). There were more embryos obtained in CF than in controls (3.1 versus 1.6, p=0.02). The number of oocytes and embryos obtained and pregnancy outcomes remained similar between DF508 homozygous group and others CFTR mutations group. The results of ART procedures and pregnancy evolution were not influenced by FEV1.

CONCLUSION: In absence of any other pathology, IUI may be first option for CF women. If insemination fails, IVF with a low dose of gonadotropins may be more appropriate to prevent the risk of hyperstimulation syndrome. FEV1 and genetic do not seem to be contributing factors in the prognosis of ART.

PMID:35265034 | PMC:PMC8898889 | DOI:10.3389/fendo.2022.773753

Nat Commun. 2022 Mar 9;13(1):1231. doi: 10.1038/s41467-022-28188-w.

ABSTRACT

Acute bacterial infections are often treated empirically, with the choice of antibiotic therapy updated during treatment. The effects of such rapid antibiotic switching on the evolution of antibiotic resistance in individual patients are poorly understood. Here we find that low-frequency antibiotic resistance mutations emerge, contract, and even go to extinction within days of changes in therapy. We analyzed Pseudomonas aeruginosa populations in sputum samples collected serially from 7 mechanically ventilated patients at the onset of respiratory infection. Combining short- and long-read sequencing and resistance phenotyping of 420 isolates revealed that while new infections are near-clonal, reflecting a recent colonization bottleneck, resistance mutations could emerge at low frequencies within days of therapy. We then measured the in vivo frequencies of select resistance mutations in intact sputum samples with resistance-targeted deep amplicon sequencing (RETRA-Seq), which revealed that rare resistance mutations not detected by clinically used culture-based methods can increase by nearly 40-fold over 5-12 days in response to antibiotic changes. Conversely, mutations conferring resistance to antibiotics not administered diminish and even go to extinction. Our results underscore how therapy choice shapes the dynamics of low-frequency resistance mutations at short time scales, and the findings provide a possibility for driving resistance mutations to extinction during early stages of infection by designing patient-specific antibiotic cycling strategies informed by deep genomic surveillance.

PMID:35264582 | DOI:10.1038/s41467-022-28188-w

Arch Dis Child Educ Pract Ed. 2022 Mar 9:edpract-2021-322446. doi: 10.1136/archdischild-2021-322446. Online ahead of print.

ABSTRACT

Children admitted to our hospital with cystic fibrosis had frequent medication errors due to polypharmacy and addition of specialist and high-risk medications despite an electronic prescribing and medicines administration system in place. We describe a multidisciplinary quality improvement project that combined a computerised order entry system (CPOE) with human factor process changes. Over 12 months, our run chart showed a 43% reduction in prescription errors. For medications prescribable via the CPOE, errors reaching the patient reduced from 50% to 29%. Electronic prescribing can be seen by clinicians as a fixed unalterable system contributing to rather than ameliorating errors. Improving safety requires whole team engagement and working closely with programmers to adapt function and influence human factors.

PMID:35264442 | DOI:10.1136/archdischild-2021-322446

J Cyst Fibros. 2022 Mar 5:S1569-1993(22)00047-9. doi: 10.1016/j.jcf.2022.02.015. Online ahead of print.

ABSTRACT

Chronic azithromycin improves outcomes in cystic fibrosis (CF), but its mechanism of action is unclear. The OPTIMIZE trial demonstrated improvement in time to first pulmonary exacerbation in children with new Pseudomonas treated with azithromycin. Azithromycin effect on systemic markers of inflammation over 18 months was assessed by change from baseline for high-sensitivity C-reactive protein, myeloperoxidase, calprotectin and absolute neutrophil count in the OPTIMIZE population. Subjects treated with chronic azithromycin or placebo had samples collected at baseline, 39 and 78 weeks of treatment. In 129 subjects, a significant decrease in high-sensitivity C-reactive protein was present at 39 weeks in the azithromycin group compared to placebo, but no significant difference between the groups at 78 weeks. No differences in change from baseline in myeloperoxidase, calprotectin or absolute neutrophil count were present at either time point. This supports the concept of a transient immunomodulatory effect for chronic azithromycin therapy in children with CF.

PMID:35260354 | DOI:10.1016/j.jcf.2022.02.015

J Cyst Fibros. 2022 Mar 5:S1569-1993(22)00049-2. doi: 10.1016/j.jcf.2022.02.017. Online ahead of print.

ABSTRACT

Airway nitric oxide (NO) deficiency is a hallmark of cystic fibrosis (CF), but the reasons for the reduced NO production in CF airways are unclear. Interleukin (IL)-1 pathway activation plays a role in early CF lung disease and is also involved in the regulation of NO synthase activity. Treatment of CF patients with the CFTR-targeting drug ivacaftor, among other beneficial effects, results in an increase in airway NO levels. In this longitudinal observational trial, we show that ivacaftor therapy leads to a significant reduction in sputum IL-1β concentration but not in other IL-1- or Th17-associated cytokines. IL-1β concentrations were closely linked to improvement in pulmonary function, measures of NO metabolism in sputum and exhaled NO. These data therefore suggest a potential interaction between transepithelial chloride conductance, IL-1β and airway NO production.

PMID:35260353 | DOI:10.1016/j.jcf.2022.02.017

Psychol Health. 2022 Mar 8:1-25. doi: 10.1080/08870446.2021.2013483. Online ahead of print.

ABSTRACT

OBJECTIVE: Treatments for cystic fibrosis (CF) are complex, labour-intensive, and perceived as highly burdensome by caregivers of children with CF. An instrument assessing burden of care is needed.

DESIGN: A stepwise, qualitative design was used to create the CLCF with caregiver focus groups, participant researchers, a multidisciplinary professional panel, and cognitive interviews.

MAIN OUTCOME MEASURES: Preliminary psychometric analyses evaluated the reliability and convergent validity of the CLCF scores. Cronbach's alpha assessed internal consistency and t-tests examined test-retest reliability. Correlations measured convergence between the Treatment Burden scale of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and the CLCF. Discriminant validity was assessed by comparing CLCF scores in one vs two-parent families, across ages, and in children with vs without Pseudomonas aeruginosa (PA).

RESULTS: Six Challenge subscales emerged from the qualitative data and the professional panel constructed a scoresheet estimating the Time and Effort required for treatments. Internal consistency and test-retest reliability were adequate. Good convergence was found between the Total Challenge score and Treatment Burden on the CFQ-R (r=-0.49, p = 0.02, n = 31). A recent PA infection signalled higher Total Challenge for caregivers (F(23)11.72, p = 0.002).

CONCLUSIONS: The CLCF, developed in partnership with parents/caregivers and CF professionals, is a timely, disease-specific burden measure for clinical research.

PMID:35259034 | DOI:10.1080/08870446.2021.2013483

Pediatr Pulmonol. 2022 Mar 8. doi: 10.1002/ppul.25884. Online ahead of print.

NO ABSTRACT

PMID:35258175 | DOI:10.1002/ppul.25884

Eur J Hum Genet. 2022 Mar 8. doi: 10.1038/s41431-022-01054-5. Online ahead of print.

ABSTRACT

Genetic screening can be hugely beneficial, yet its expansion poses clinical and ethical challenges due to results of uncertain clinical relevance (such as 'cystic fibrosis screen positive, inconclusive diagnosis'/CFSPID). This review systematically identifies, appraises, and synthesises the qualitative research on experiences of receiving results of uncertain clinical relevance from population genetic screening. Eight databases were systematically searched for original qualitative research using the SPIDER framework, and checked against inclusion criteria by the research team and an independent researcher. Nine papers were included (from USA, Canada, UK, New Zealand). PRISMA, ENTREQ, and EMERGE guidance were used to report. Quality was appraised using criteria for qualitative research. All papers focused on parental responses to uncertain results from newborn screening. Data were synthesised using meta-ethnography and first- and second-order constructs. Findings suggest that results of uncertain clinical relevance are often experienced in the same way as a 'full-blown' diagnosis. This has significant emotional and behavioural impact, for example adoption of lifestyle-altering disease-focused behaviours. Analysis suggests this may be due to the results not fitting a common medical model, leading recipients to interpret the significance of the result maladaptively. Findings suggest scope for professionals to negotiate and reframe uncertain screening results. Clearer initial communication is needed to reassure recipients there is no immediate severe health risk from these types of results. Public understanding of an appropriate medical model, that accounts for uncertain genetic screening results in a non-threatening way, may be key to maximising the benefits of genomic medicine and minimising potential psychological harm.

PMID:35256770 | DOI:10.1038/s41431-022-01054-5

Curr Opin Pulm Med. 2022 Mar 7. doi: 10.1097/MCP.0000000000000871. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: The global prevalence of asthma continues to increase; however, asthma remains under-diagnosed and under-treated. This results in a significant burden on the healthcare system and preventable patient morbidity and mortality. Over-diagnosis of asthma based on clinical history alone also complicates patient management. This heightens the importance of a prompt and accurate asthma diagnosis. Therefore, a review of the literature was performed regarding both objective diagnostic testing for asthma and using patient-reported outcome measures.

RECENT FINDINGS: The cornerstone of asthma diagnosis remains spirometry with testing for bronchodilator reversibility testing for pediatric and adult populations. This test may need to be repeated at multiple time points due to its low sensitivity. Peak flow measurement, fractional exhaled nitric oxide testing, and allergy testing are useful adjuncts to the diagnosis and phenotyping of asthma. Bronchoprovocation testing is reserved for people with high clinical suspicion for asthma, but negative spirometry. Novel noninvasive testing modalities may play a diagnostic role in the future. The advent of remote digital health monitoring technology has resulted in revisiting patient-reported outcome measures for the diagnosis and monitoring of asthma.

SUMMARY: Overall, improved diagnostic tools for asthma are crucial for earlier recognition and treatment of the disease and improved patient care outcomes worldwide.

PMID:35256554 | DOI:10.1097/MCP.0000000000000871

J Cyst Fibros. 2022 Feb 21:S1569-1993(22)00044-3. doi: 10.1016/j.jcf.2022.02.012. Online ahead of print.

ABSTRACT

BACKGROUND: People with cystic fibrosis (pwCF) may be at risk of complications from COVID-19 but the impact of COVID-19 on pwCF remains unknown.

METHODS: We conducted a multicenter retrospective cohort study to assess the impact of the COVID-19 pandemic first wave on pwCF in the New York metropolitan area (NY) from March 1, 2020 to August 31, 2020. Objectives were to determine (1) the prevalence of COVID-19 by PCR and IgG antibody testing, (2) the clinical characteristics of COVID-19, (3) delay in routine outpatient care, and (4) the effect on anxiety and depression in pwCF.

RESULTS: There were 26 COVID-19 cases diagnosed by PCR or antibody testing among the study cohort of 810 pwCF. The prevalence of COVID-19 by PCR (1.6%) and IgG antibody (12.2%) testing was low. 58% of cases were asymptomatic and 82% were managed at home. 8% were hospitalized and 1 person died. 89% of pwCF experienced delay in care. The prevalence of anxiety increased from 43% baseline to 58% during the pandemic (P<0.01). In post-hoc analysis, the proportion of patients with diabetes (38% versus 16%, P<0.01) and pancreatic insufficiency (96% versus 66%, P<0.01) were higher while CFTR modulator use was lower (46% versus 65%, P = 0.05) in pwCF who tested positive for COVID-19.

CONCLUSIONS: The prevalence of COVID-19 among pwCF in NY during the pandemic first wave was low and most cases were managed at home. CFTR modulators may be protective. PwCF experienced delay in routine care and increased anxiety.

PMID:35256307 | DOI:10.1016/j.jcf.2022.02.012

J Cyst Fibros. 2022 Feb 16:S1569-1993(22)00041-8. doi: 10.1016/j.jcf.2022.02.009. Online ahead of print.

NO ABSTRACT

PMID:35256306 | DOI:10.1016/j.jcf.2022.02.009

Curr Opin Pharmacol. 2022 Mar 4;63:102201. doi: 10.1016/j.coph.2022.102201. Online ahead of print.

ABSTRACT

The greatest challenge of current biomedicine is to identify curative therapies for every disease in a personalized way so that every individual gets benefit. To that end, however, we need fully understand mechanisms of disease that will drive the design of novel therapies and innovative approaches. For rare diseases (RDs) which individually affect low numbers of people (< 1:2000), but together, affect 300 million (∼10% of the world population) the constraints are greater. This is because: 1) there is limited knowledge on RD physiopathology; 2) the low number of patients strongly limits clinical trials; 3) there is low commercial interest by pharma; 4) when specific drugs reach the market, their high cost precludes their reaching all those who need them. Several possibilities that can help mitigate these barriers are discussed here, including orphan drug designation, drug repurposing, break-down into theratypes (as currently in place for Cystic Fibrosis), or novel precision-medicine-based approaches.

PMID:35255452 | DOI:10.1016/j.coph.2022.102201

JAMA Netw Open. 2022 Mar 1;5(3):e220749. doi: 10.1001/jamanetworkopen.2022.0749.

NO ABSTRACT

PMID:35254436 | DOI:10.1001/jamanetworkopen.2022.0749

JAMA Netw Open. 2022 Mar 1;5(3):e220740. doi: 10.1001/jamanetworkopen.2022.0740.

ABSTRACT

IMPORTANCE: The prevalence of overweight (body mass index [BMI] = 25-29.9 [calculated as weight in kilograms divided by height in meters squared]) and obesity (BMI ≥30) is increasing among patients with cystic fibrosis (CF). However, it is unclear whether there is a benefit associated with increasing weight compared with the reference range (ie, normal) in CF.

OBJECTIVE: To evaluate the association of altered BMI or body composition and clinical outcomes in patients with CF.

DATA SOURCES: For this systematic review and meta-analysis, the literature search was conducted November 2, 2020, of 3 databases: MEDLINE (via PubMed), Embase, and Cochrane Central Register of Controlled Trials.

STUDY SELECTION: Patients older than 2 years diagnosed with CF with altered body composition or BMI were compared with patients having the measured parameters within the reference ranges. Records were selected by title, abstract, and full text; disagreements were resolved by consensus. Cohort studies and conference abstracts were eligible; articles with no original data and case reports were excluded.

DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted data, which were validated by a third author. Studies containing insufficient poolable numerical data were included in the qualitative analysis. A random-effects model was applied in all analyses.

MAIN OUTCOMES AND MEASURES: Pulmonary function, exocrine pancreatic insufficiency (PI), and CF-related diabetes (CFRD) were investigated as primary outcomes. Odds ratios (ORs) or weighted mean differences (WMDs) with 95% CIs were calculated. The hypothesis was formulated before data collection.

RESULTS: Of 10 524 records identified, 61 met the selection criteria and were included in the qualitative analysis. Of these, 17 studies were included in the quantitative synthesis. Altogether, 9114 patients were included in the systematic review and meta-analysis. Overweight (WMD, -8.36%; 95% CI, -12.74% to -3.97%) and obesity (WMD, -12.06%; 95% CI, -23.91% to -0.22%) were associated with higher forced expiratory volume in the first second of expiration compared with normal weight. The odds for CFRD and PI were more likely in patients of normal weight (OR, 1.49; 95% CI, 1.10 to 2.00) than in those who were overweight (OR, 4.40; 95% CI, 3.00 to 6.45). High heterogeneity was shown in the analysis of pulmonary function (I2 = 46.7%-85.9%).

CONCLUSIONS AND RELEVANCE: The findings of this systematic review and meta-analysis suggest that the currently recommended target BMI in patients with CF should be reconsidered. Studies with long-term follow-up are necessary to assess the possible adverse effects of higher BMI or higher fat mass in patients with CF.

PMID:35254432 | DOI:10.1001/jamanetworkopen.2022.0740

Front Cell Infect Microbiol. 2022 Feb 16;12:819554. doi: 10.3389/fcimb.2022.819554. eCollection 2022.

ABSTRACT

Cystic fibrosis (CF) human and mouse macrophages are defective in their ability to clear bacteria such as Burkholderia cenocepacia. The autophagy process in CF (F508del) macrophages is halted, and the underlying mechanism remains unclear. Furthermore, the role of CFTR in maintaining the acidification of endosomal and lysosomal compartments in CF cells has been a subject of debate. Using 3D reconstruction of z-stack confocal images, we show that CFTR is recruited to LC3-labeled autophagosomes harboring B. cenocepacia. Using several complementary approaches, we report that CF macrophages display defective lysosomal acidification and degradative function for cargos destined to autophagosomes, whereas non-autophagosomal cargos are effectively degraded within acidic compartments. Notably, treatment of CF macrophages with CFTR modulators (tezacaftor/ivacaftor) improved the autophagy flux, lysosomal acidification and function, and bacterial clearance. In addition, CFTR modulators improved CFTR function as demonstrated by patch-clamp. In conclusion, CFTR regulates the acidification of a specific subset of lysosomes that specifically fuse with autophagosomes. Therefore, our study describes a new biological location and function for CFTR in autophago-lysosomes and clarifies the long-standing discrepancies in the field.

PMID:35252032 | PMC:PMC8890004 | DOI:10.3389/fcimb.2022.819554

Respir Med. 2022 Feb 25:106778. doi: 10.1016/j.rmed.2022.106778. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is a common respiratory pathogen found in patients with cystic fibrosis (CF), contributing to increased hospitalization, more rapid progression of CF lung disease, and increased risk of death. Guidelines recommend early therapy using tobramycin inhaled solution (TIS) or inhaled powder (TIP). Both TIS and TIP treatment regimens have demonstrated positive clinical outcomes in efficacy and safety, including improvements in FEV1, decreased sputum P. aeruginosa density, decreased rates in antipseudomonal antibiotic use, and reduced rates of hospitalizations due to respiratory events. In a comparison of patient preference for TIS versus TIP, a patient survey cited time savings and convenience as preferences for TIP. However, both TIP and TIS offer advantages that may benefit patients and increase treatment adherence depending on patient circumstances. TIS may be suitable for younger patients at home where parents and caregivers may better control proper administration, older individuals, and those with low FEV1. Dry powder inhalers are suitable when patients have less time to commit to their self-care (eg, patients who work, are remotely located, return home late, or are on vacation), and can reduce the patient treatment burden compared with nebulized delivery. In this expert review, we summarize the available data on tobramycin regarding its molecular characteristics, mechanism of action, and efficacy and safety for the treatment of acute and chronic P. aeruginosa infection.

PMID:35249787 | DOI:10.1016/j.rmed.2022.106778

Arch Bronconeumol. 2022 Jan;58(1):22-29. doi: 10.1016/j.arbres.2021.06.001. Epub 2021 Jun 17.

ABSTRACT

BACKGROUND: Children's diffuse lung disease, also known as children's Interstitial Lung Diseases (chILD), are a heterogeneous group of rare diseases with relevant morbidity and mortality, which diagnosis and classification are very complex. Epidemiological data are scarce. The aim of this study was to analyse incidence and prevalence of chILD in Spain.

METHODS: Multicentre observational prospective study in patients from 0 to 18 years of age with chILD to analyse its incidence and prevalence in Spain, based on data reported in 2018 and 2019.

RESULTS: A total of 381 cases with chILD were notified from 51 paediatric pulmonology units all over Spain, covering the 91.7% of the paediatric population. The average incidence of chILD was 8.18 (CI 95% 6.28-10.48) new cases/million of children per year. The average prevalence of chILD was 46.53 (CI 95% 41.81-51.62) cases/million of children. The age group with the highest prevalence were children under 1 year of age. Different types of disorders were seen in children 2-18 years of age compared with children 0-2 years of age. Most frequent cases were: primary pulmonary interstitial glycogenosis in neonates (17/65), neuroendocrine cell hyperplasia of infancy in infants from 1 to 12 months (44/144), idiopathic pulmonary haemosiderosis in children from 1 to 5 years old (13/74), hypersensitivity pneumonitis in children from 5 to 10 years old (9/51), and scleroderma in older than 10 years old (8/47).

CONCLUSIONS: We found a higher incidence and prevalence of chILD than previously described probably due to greater understanding and increased clinician awareness of these rare diseases.

PMID:35249699 | DOI:10.1016/j.arbres.2021.06.001

Mol Cell Pediatr. 2022 Mar 5;9(1):4. doi: 10.1186/s40348-022-00136-0.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is the most common genetic disorder in the Caucasian population. Despite remarkable improvements in morbidity and mortality during the last decades, the disease still limits survival and reduces quality of life of affected patients. Moreover, CF still represents substantial economic burden for healthcare systems. Inflammation and infection already start in early life and play important roles in pulmonary impairment. The aim of this study is to analyze the potential role of DMBT1, a protein with functions in inflammation, angiogenesis, and epithelial differentiation, in CF.

RESULTS: Immunohistochemically DMBT1 protein expression was upregulated in lung tissues of CF patients compared to healthy controls. Additionally, pulmonary expression of Dmbt1 was approximately 6-fold increased in an established transgenic mouse model of CF-like lung disease (ENaC tg) compared to wild-type mice as detected by qRT-PCR. Since acetylcysteine (ACC) has been shown to reduce inflammatory markers in the airways, its potential influence on DMBT1 expression was analyzed. A549 cells stably transfected with an expression plasmid encoding the largest (8kb) DMBT1 variant (DMBT1+ cells) or an empty vector control (DMBT1- cells) and incubated with ACC both showed significantly reduced DMBT1 concentrations in the culture medium (p = 0.0001). To further elucidate the function of DMBT1 in pulmonary airways, respiratory epithelial cells were examined by phase contrast microscopy. Addition of human recombinant DMBT1 resulted in altered cilia motility and irregular beat waves (p < 0.0001) suggesting a potential effect of DMBT1 on airway clearance.

CONCLUSIONS: DMBT1 is part of inflammatory processes in CF and may be used as a potential biomarker for CF lung disease and a potential tool to monitor CF progression. Furthermore, DMBT1 has a negative effect on ciliary motility thereby possibly compromising airway clearance. Application of ACC, leading to reduced DMBT1 concentrations, could be a potential therapeutic option for CF patients.

PMID:35249163 | DOI:10.1186/s40348-022-00136-0

J Cyst Fibros. 2022 Mar 2:S1569-1993(22)00043-1. doi: 10.1016/j.jcf.2022.02.011. Online ahead of print.

ABSTRACT

BACKGROUND: A decrease in the lumacaftor-mediated increase in F508del-CFTR function and expression upon prolonged exposure to ivacaftor (VX-770) has previously been described. However, the efficacy observed with ivacaftor-containing CFTR modulator therapies in vivo is in conflict with these reports. We hypothesized that a portion of the apparent decrease in CFTR function observed after prolonged ivacaftor exposure in vitro was due to an increase in constitutive CFTR-mediated ion transport.

METHODS: Human nasal epithelial (HNE) cells were obtained by brushings from three CF individuals homozygous for the F508del CFTR mutation. Differentiated epithelia were pre-treated with prolonged (24 h) exposure to either lumacaftor (VX-809; 3 µM), tezacaftor (VX-661; 3 µM), elexacaftor (VX-445; 3 µM), and/or ivacaftor (0.1-6.4 µM) or DMSO (vehicle control), and CFTR function was assayed by Ussing chamber electrophysiology.

RESULTS: In cells treated with lumacaftor, constitutive CFTR activity was not increased at any concentration of co-treatment with ivacaftor. Constitutive CFTR activity was also unchanged in cells treated with the combination of tezacaftor and elexacaftor. An increase in constitutive CFTR activity above the DMSO controls was only observed in cells treated with the combination of tezacaftor and elexacaftor and co-treated with at least 0.1 µM ivacaftor.

CONCLUSIONS: These results demonstrate that ivacaftor is a critical component in the triple combination therapy along with tezacaftor and elexacaftor to increase constitutive CFTR function. This work further elucidates the mechanism of action of the effective triple combination therapeutic that is now the primary clinical tool in treating CF.

PMID:35248469 | DOI:10.1016/j.jcf.2022.02.011

J Hosp Infect. 2022 Mar 2:S0195-6701(22)00069-X. doi: 10.1016/j.jhin.2022.02.018. Online ahead of print.

NO ABSTRACT

PMID:35247495 | DOI:10.1016/j.jhin.2022.02.018