J Diabetes Complications. 2021 Feb 25:107887. doi: 10.1016/j.jdiacomp.2021.107887. Online ahead of print.

NO ABSTRACT

PMID:33775536 | DOI:10.1016/j.jdiacomp.2021.107887

Lancet Respir Med. 2021 Mar 24:S2213-2600(21)00162-4. doi: 10.1016/S2213-2600(21)00162-4. Online ahead of print.

NO ABSTRACT

PMID:33773122 | DOI:10.1016/S2213-2600(21)00162-4

J Clin Psychol Med Settings. 2021 Mar 27. doi: 10.1007/s10880-021-09770-8. Online ahead of print.

ABSTRACT

Adults with heart failure and transplant are at increased risk for psychiatric comorbidities. The prevalence and impact of psychiatric comorbidities have not been well studied in pediatric heart failure and transplant. This quality improvement project sought to evaluate the feasibility of utilizing electronic mental health screening measures during pediatric heart failure and transplant clinics and to explore the prevalence and severity of self-reported depressive, anxiety, and suicidal ideation symptoms. Patients aged 11 years and older who presented to a pediatric heart failure and transplant clinic were administered the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7). Medical chart review and a survey were used to examine additional variables of interest. There were no significant differences in moderate and severe mental health symptoms between gender, medical diagnoses, or those with recent hospitalizations. Pediatric patients with heart failure or transplant reported higher prevalence of anxiety and depressive symptoms, and similar suicidal ideation compared to the general adolescent population. Moreover, rates of depression and anxiety symptoms as well as suicidal ideation were comparable to pediatric patients with diabetes, lupus, inflammatory bowel disease, and cystic fibrosis. Results suggest electronic mental health screening is feasible for use during outpatient cardiology clinic visits and provides valuable mental health information.

PMID:33772706 | DOI:10.1007/s10880-021-09770-8

Sci Rep. 2021 Mar 26;11(1):7008. doi: 10.1038/s41598-021-86404-x.

ABSTRACT

Dietary fiber functions as a prebiotic to determine the gut microbe composition. The gut microbiota influences the metabolic functions and immune responses in human health. The gut microbiota and metabolites produced by various dietary components not only modulate immunity but also impact various organs. Although recent findings have suggested that microbial dysbiosis is associated with several respiratory diseases, including asthma, cystic fibrosis, and allergy, the role of microbiota and metabolites produced by dietary nutrients with respect to pulmonary disease remains unclear. Therefore, we explored whether the gut microbiota and metabolites produced by dietary fiber components could influence a cigarette smoking (CS)-exposed emphysema model. In this study, it was demonstrated that a high-fiber diet including non-fermentable cellulose and fermentable pectin attenuated the pathological changes associated with emphysema progression and the inflammatory response in CS-exposed emphysema mice. Moreover, we observed that different types of dietary fiber could modulate the diversity of gut microbiota and differentially impacted anabolism including the generation of short-chain fatty acids, bile acids, and sphingolipids. Overall, the results of this study indicate that high-fiber diets play a beneficial role in the gut microbiota-metabolite modulation and substantially affect CS-exposed emphysema mice. Furthermore, this study suggests the therapeutic potential of gut microbiota and metabolites from a high-fiber diet in emphysema via local and systemic inflammation inhibition, which may be useful in the development of a new COPD treatment plan.

PMID:33772084 | DOI:10.1038/s41598-021-86404-x

J Mol Biol. 2021 Mar 23:166955. doi: 10.1016/j.jmb.2021.166955. Online ahead of print.

ABSTRACT

ABC-transporters transport a wealth of molecules across membranes and consist of transmembrane and cytosolic domains. Their activity cycle involves a tightly regulated and concerted domain choreography. Regulation is driven by the cytosolic domains and function by the transmembrane domains. Folding of these polytopic multidomain proteins to their functional state is a challenge for cells, which is mitigated by co-translational and sequential events. We here reveal the first stages of co-translational domain folding and assembly of CFTR, the ABC-transporter defective in the most abundant rare inherited disease cystic fibrosis. We have combined biosynthetic radiolabeling with protease-susceptibility assays and domain-specific antibodies. The most N-terminal domain, TMD1 (transmembrane domain 1), folds both its hydrophobic and soluble helices during translation: the transmembrane helices pack tightly and the cytosolic N- and C-termini assemble with the first cytosolic helical loop ICL1, leaving only ICL2 exposed. This N-C-ICL1 assembly is strengthened by two independent events: i) assembly of ICL1 with the N-terminal subdomain of the next domain, cytosolic NBD1 (nucleotide-binding domain 1); and ii) in the presence of corrector drug VX-809, which rescues cell-surface expression of a range of disease-causing CFTR mutants. Both lead to increased shielding of the CFTR N-terminus, and their additivity implies different modes of action. Early assembly of NBD1 and TMD1 is essential for CFTR folding and positions both domains for the required assembly with TMD2. Altogether, we have gained insights into this first, nucleating, VX-809-enhanced domain-assembly event during and immediately after CFTR translation, involving structures conserved in type-I ABC exporters.

PMID:33771570 | DOI:10.1016/j.jmb.2021.166955

Pediatr Phys Ther. 2021 Apr 1;33(2):E99-E102. doi: 10.1097/PEP.0000000000000790.

ABSTRACT

PURPOSE: This case report describes the identification and treatment of costochondritis with suspected neural entrapment in a 14-year-old individual diagnosed with cystic fibrosis.

SUMMARY OF KEY POINTS: The individual discussed in this report had resolution of his chest pain with additional improvement in pulmonary function test results.

STATEMENT OF CONCLUSION AND RECOMMENDATIONS FOR CLINICAL PRACTICE: This case supports the need for musculoskeletal and neuromuscular screening and intervention for patients with cystic fibrosis. The success of the intervention suggests that when traditional approaches to treatment of costochondritis fail, use of myofascial release at the accessory muscles of breathing could be beneficial.

PMID:33770802 | DOI:10.1097/PEP.0000000000000790

Curr Microbiol. 2021 Mar 26. doi: 10.1007/s00284-021-02458-0. Online ahead of print.

ABSTRACT

Polymicrobial lung infections in individuals with Cystic Fibrosis (CF) contribute to the complexity of this disease and are a major cause of morbidity and mortality in the CF community. The microorganisms most commonly associated with severe airway infections in individuals with CF are the opportunistic pathogens S. aureus, P. aeruginosa and bacteria from the Burkholderia cepacia complex (Bcc), particularly B. cenocepacia and B. multivorans. Three Bcc strains, two S. aureus wild-type strains, and two derivative mutants were used to investigate the interplay between S. aureus and Bcc with a focus on the hemolytic activity of Bcc. Our results revealed that extracellular products from S. aureus potentiated the hemolysis of Bcc strains. Moreover, this effect was influenced by the composition of the medium in which S. aureus is grown. These findings contribute towards the understanding of the impact of interactions between S. aureus and Bcc and their possible implications in the context of co-infections by these pathogens in individuals with CF.

PMID:33770213 | DOI:10.1007/s00284-021-02458-0

Chemistry. 2021 Mar 26. doi: 10.1002/chem.202100252. Online ahead of print.

ABSTRACT

Burkholderia cenocepacia is an opportunistic gram-negative bacterium that causes infections in patients suffering from chronic granulomatous diseases and cystic fibrosis. It displays significant morbidity and mortality due to extreme resistance to almost all clinically useful antibiotics. The bacterial lectin BC2L-C expressed in B. cenocepacia is an interesting drug target involved in bacterial adhesion and subsequent deadly infection to the host. We solved the first high resolution crystal structure of the apo form of the lectin N-terminal domain (BC2L-C-nt) and compared it with the ones complexed with carbohydrate ligands. Virtual screening of a small fragment library identified potential hits predicted to bind in the vicinity of the fucose binding site. A series of biophysical techniques and a X-ray crystallographic screening were employed to validate the interaction of the hits with the protein domain. The X-ray structure of BC2L-C-nt complexed with one of the identified active fragments confirmed the ability of the site computationally identified to host drug-like fragments. The fragment affinity could be determined by titration microcalorimetry. These structure-based strategies further provide an opportunity to elaborate the fragments into high affinity anti-adhesive glycomimetics, as therapeutic agents against B. cenocepacia.

PMID:33769626 | DOI:10.1002/chem.202100252

Clin Case Rep. 2021 Jan 15;9(3):1379-1382. doi: 10.1002/ccr3.3781. eCollection 2021 Mar.

ABSTRACT

As diagnostic algorithms for cystic fibrosis (CF) continue to evolve, education of general practitioners is essential to prevent delayed diagnosis of CF and allow prompt referral to CF centers. For patients suffering from allergic bronchopulmonary aspergillosis (ABPA), CF should be at the top of the differential diagnosis.

PMID:33768849 | PMC:PMC7981717 | DOI:10.1002/ccr3.3781

Mol Ther Methods Clin Dev. 2021 Feb 27;21:94-106. doi: 10.1016/j.omtm.2021.02.020. eCollection 2021 Jun 11.

ABSTRACT

Despite significant advances in cystic fibrosis (CF) treatments, a one-time treatment for this life-shortening disease remains elusive. Stable complementation of the disease-causing mutation with a normal copy of the CF transmembrane conductance regulator (CFTR) gene fulfills that goal. Integrating lentiviral vectors are well suited for this purpose, but widespread airway transduction in humans is limited by achievable titers and delivery barriers. Since airway epithelial cells are interconnected through gap junctions, small numbers of cells expressing supraphysiologic levels of CFTR could support sufficient channel function to rescue CF phenotypes. Here, we investigated promoter choice and CFTR codon optimization (coCFTR) as strategies to regulate CFTR expression. We evaluated two promoters-phosphoglycerate kinase (PGK) and elongation factor 1-α (EF1α)-that have been safely used in clinical trials. We also compared the wild-type human CFTR sequence to three alternative coCFTR sequences generated by different algorithms. With the use of the CFTR-mediated anion current in primary human CF airway epithelia to quantify channel expression and function, we determined that EF1α produced greater currents than PGK and identified a coCFTR sequence that conferred significantly increased functional CFTR expression. Optimized promoter and CFTR sequences advance lentiviral vectors toward CF gene therapy clinical trials.

PMID:33768133 | PMC:PMC7973238 | DOI:10.1016/j.omtm.2021.02.020

Nat Med. 2021 Mar 25. doi: 10.1038/s41591-021-01296-8. Online ahead of print.

ABSTRACT

Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.

PMID:33767405 | DOI:10.1038/s41591-021-01296-8

Sci Rep. 2021 Mar 25;11(1):6842. doi: 10.1038/s41598-021-83240-x.

ABSTRACT

C407 is a compound that corrects the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein carrying the p.Phe508del (F508del) mutation. We investigated the corrector effect of c407 and its derivatives on F508del-CFTR protein. Molecular docking and dynamics simulations combined with site-directed mutagenesis suggested that c407 stabilizes the F508del-Nucleotide Binding Domain 1 (NBD1) during the co-translational folding process by occupying the position of the p.Phe1068 side chain located at the fourth intracellular loop (ICL4). After CFTR domains assembly, c407 occupies the position of the missing p.Phe508 side chain. C407 alone or in combination with the F508del-CFTR corrector VX-809, increased CFTR activity in cell lines but not in primary respiratory cells carrying the F508del mutation. A structure-based approach resulted in the synthesis of an extended c407 analog G1, designed to improve the interaction with ICL4. G1 significantly increased CFTR activity and response to VX-809 in primary nasal cells of F508del homozygous patients. Our data demonstrate that in-silico optimized c407 derivative G1 acts by a mechanism different from the reference VX-809 corrector and provide insights into its possible molecular mode of action. These results pave the way for novel strategies aiming to optimize the flawed ICL4-NBD1 interface.

PMID:33767236 | DOI:10.1038/s41598-021-83240-x

Sci Rep. 2021 Mar 25;11(1):6845. doi: 10.1038/s41598-021-85592-w.

ABSTRACT

Strict anaerobes are undeniably important residents of the cystic fibrosis (CF) lung but are still unknowns. The main objectives of this study were to describe anaerobic bacteria diversity in CF airway microbiota and to evaluate the association with lung function. An observational study was conducted during eight months. A hundred and one patients were enrolled in the study, and 150 sputum samples were collected using a sterile sample kit designed to preserve anaerobic conditions. An extended-culture approach on 112 sputa and a molecular approach (quantitative PCR targeting three of the main anaerobic genera in CF lung: Prevotella, Veillonella, and Fusobacterium) on 141 sputa were developed. On culture, 91.1% of sputa were positive for at least one anaerobic bacterial species, with an average of six anaerobic species detected per sputum. Thirty-one anaerobic genera and 69 species were found, which is the largest anaerobe diversity ever reported in CF lungs. Better lung function (defined as Forced Expiratory Volume in one second > 70%) was significantly associated with higher quantification of Veillonella. These results raise the question of the potential impact of anaerobes on lung function.

PMID:33767218 | DOI:10.1038/s41598-021-85592-w

Eur J Pediatr. 2021 Mar 25. doi: 10.1007/s00431-021-04011-4. Online ahead of print.

ABSTRACT

Patients with cystic fibrosis (CF) have a higher incidence of celiac disease (CD) than the healthy population; however, the actual incidence of coexisting CF and CD is unclear. In this report, we aimed to evaluate the frequency of CD and CF coexistence and to assess the clinical findings of affected patients during follow-up. We conducted a retrospective review of patients with CF to reveal the frequency of CD and also investigated the clinical characteristics and clinical response to gluten-free diet in patients with CD. The incidence of CD in 515 patients with CF was 1.4%. The median age at the time of CF diagnosis was 2 months (1-6 months). CD was diagnosed in six patients with poor weight gain, fatty stools, and low z score for BMI and one patient with poor weight gain despite a high protein and calorie diet and pancreatic enzyme replacement. The median age of CD diagnosis was 8 years (2-12 years). Except for one patient who was recently diagnosed, the other six patients gained weight and their accompanying symptoms resolved after starting a gluten-free diet.Conclusion: CD should be investigated in patients with CF in the presence of inadequate weight and/or height gain or poor control of malabsorption symptoms despite appropriate and adequate nutritional and enzyme replacement treatment. What is Known: • CFTR dysfunction may be a risk factor for CD, due to increased intestinal permeability and intestinal inflammation, pancreatic exocrine insufficiency that results in higher antigen load and increased antibodies against to nutritional antigens such as anti-gliadin IgA antibodies. • Although coexistence of CF and CD are rare in the same patient; there is still no consensus on when children with CF should be screened for CD. What is New: • Physicians should consider the investigation of CD in patients with CF, in the presence of inadequate weight and/or height gain or poor control of malabsorption symptoms despite appropriate and adequate nutritional and enzyme replacement treatment. • CFTR dysfunction has been emphasized to develop susceptibility to CD, and patients with CF who have persistent gastrointestinal symptoms despite appropriate and adequate nutritional and enzyme replacement treatment should be screened for CD.

PMID:33765186 | DOI:10.1007/s00431-021-04011-4

Pulm Med. 2021 Mar 9;2021:5581812. doi: 10.1155/2021/5581812. eCollection 2021.

ABSTRACT

BACKGROUND: Regular physical activity plays an important role in the treatment of patients with cystic fibrosis (CF). This study is aimed at investigating the effects of a 12-month partially supervised exercise program on attributes of health-related and motor performance fitness, lung function (ppFEV1), BMI, and habitual physical activity (HPA, steps/day) in adults with CF.

METHODS: Attributes of health-related and motor performance fitness were examined at the beginning (T0), after 6 (T1), and 12 months (T2) on the basis of five test items: forward bend (FB), bent knee hip extension (HE), plank leg raise (PLR), standing long jump (SLJ), and standing on one leg (OLS). Additionally, we recorded HPA by accelerometry, peak exercise performance (W peak) by an incremental cycle test, ppFEV1, and BMI. During the first six months, there was close supervision by an experienced sport therapist.

RESULTS: 26 CF patients (8 female, mean age 26.5 ± 7.9 years; ppFEV1 53.7 ± 21.0) completed the exercise program. Significant improvements were recorded from T0 to T1 (FB: p ≤ 0.05; PLR, OLS: p ≤ 0.01) and from T0 to T2 (FB, PLR: p ≤ 0.01 and HE, OLS: p ≤ 0.05). W peak, ppFEV1, BMI, and HPA showed no significant improvement between the single test points and over the entire study period (all p > 0.05).

CONCLUSION: Our results show trainability of adults with CF in aspects of health-related and motor performance fitness during a partially supervised exercise program. Close supervision positively influences the results. Using a simple test setup seems to be a promising tool for evaluating the effects of exercise programs in CF and could serve as an additional outcome parameter in future clinical trials. Trial registration: ClinicalTrials.gov (retrospectively registered May 8, 2018).

PMID:33763240 | PMC:PMC7964122 | DOI:10.1155/2021/5581812

BMJ Open Respir Res. 2021 Mar;8(1):e000842. doi: 10.1136/bmjresp-2020-000842.

ABSTRACT

BACKGROUND: Although asthma is the most commonly diagnosed respiratory disease, its pathogenesis is complex, involving both genetic and environmental factors. A role for the respiratory microbiome in modifying asthma severity has been recently recognised. Airway colonisation by Pneumocystis jirovecii has previously been associated with multiple chronic lung diseases, including chronic obstructive pulmonary disease (COPD) and severe asthma (SA). Decreased incidence of Pneumocystis pneumonia in HIV-infected individuals and reduced severity of COPD is associated with naturally occurring antibody responses to the Pneumocystis antigen, Kexin (KEX1).

METHODS: 104 paediatric patients were screened for KEX1 IgG reciprocal end point titre (RET), including 51 with SA, 20 with mild/moderate asthma, 20 non-asthma and 13 with cystic fibrosis (CF) in a cross-sectional study.

RESULTS: Patients with SA had significantly reduced Pneumocystis KEX1 titres compared with patients with mild/moderate asthma (p=0.018) and CF (p=0.003). A binary KEX1 RET indicator was determined at a threshold of KEX1 RET=1000. Patients with SA had 4.40 (95% CI 1.28 to 13.25, p=0.014) and 17.92 (95% CI 4.15 to 66.62, p<0.001) times the odds of falling below that threshold compared with mild/moderate asthma and patients with CF, respectively. Moreover, KEX1 IgG RET did not correlate with tetanus toxoid IgG (r=0.21, p=0.82) or total IgE (r=0.03, p=0.76), indicating findings are specific to antibody responses to KEX1.

CONCLUSIONS: Paediatric patients with SA may be at higher risk for chronic Pneumocystis infections and asthma symptom exacerbation due to reduced levels of protective antibodies. Plasma KEX1 IgG titre may be a useful parameter in determining the clinical course of treatment for paediatric patients with asthma.

PMID:33762359 | DOI:10.1136/bmjresp-2020-000842

J Cyst Fibros. 2021 Mar 21:S1569-1993(21)00055-2. doi: 10.1016/j.jcf.2021.03.006. Online ahead of print.

ABSTRACT

BACKGROUND: With the improved health afforded by cystic fibrosis transmembrane conductance regulator (CFTR) modulators, pregnancy rates are increasing in women with CF. In animal reproductive models, the three components of elexacaftor-tezacaftor-ivacaftor (ETI) did not cause teratogenicity at normal human doses. Although the limited human data available in the literature for previously approved modulators did not suggest cause for concern, there is currently no data in the literature regarding use of ETI in pregnant women. Thus, the decision to continue therapy during pregnancy (with the associated unknown fetal impact) versus discontinuing therapy (with the known risk of maternal health decline) is challenging.

METHODS: CF Center staff completed an anonymous questionnaire regarding pregnancy and infant outcomes for women who used ETI during pregnancy and/or lactation.

RESULTS: Of 45 ETI-exposed pregnancies reported to date, complications in 2 mothers and in 3 infants (2 born to mothers with poorly controlled diabetes) were rated by clinicians as unknown (possible) or suspected relatedness to ETI use. Two women terminated unplanned pregnancies. Miscarriage rates were consistent with that known in the general U.S.

POPULATION: Five of the six women who discontinued ETI out of concern for unknown fetal risk restarted because of clinical deterioration. No infant cataracts were reported though only two infants were formally evaluated.

CONCLUSIONS: In the context of the known increased rate of complications in women with CF and their infants, data from this retrospective survey is reassuring for women who choose to continue ETI during pregnancy. However, a large, multi-center prospective study is needed to assess impact of use of ETI in pregnancy.

PMID:33762125 | DOI:10.1016/j.jcf.2021.03.006

Ital J Pediatr. 2021 Mar 24;47(1):71. doi: 10.1186/s13052-021-01020-9.

ABSTRACT

Gastrointestinal diseases such as celiac disease, functional gastrointestinal disorders (FGIDs), inflammatory bowel disease (IBDs) and acute or chronic diarrhea are quite frequent in the pediatric population. The approach, the diagnosis and management can be changed in the 2019 coronavirus disease (COVID-19) pandemic era. This review has focused on: i) the current understanding of digestive involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected children and adolescents and the clinical implications of COVID-19 for pediatric gastroenterologists, ii) the impact of COVID-19 on the clinical approach to patients with pre-existing or onset diseases, including diagnosis and treatment, and iii) the role and limited access to the instrumental diagnosis such as digestive endoscopy. To date, it is unclear if immunosuppression in patients with IBD and chronic liver disease represents a risk factor for adverse outcomes. Scheduled outpatient follow-up visits may be postponed, especially in patients in remission. Conversely, telemedicine services are strongly recommended. The introduction of new therapeutic regimens should be made on an individual basis, discussing the benefits and risks with each patient. Furthermore, psychological care in all children with chronic disease and their parents should be ensured. All non-urgent and elective endoscopic procedures may be postponed as they must be considered at high risk of viral transmission. Finally, until SARS-CoV-2 vaccination is not available, strict adherence to standard social distancing protocols and the use of personal protective equipment should continue to be recommended.

PMID:33761992 | DOI:10.1186/s13052-021-01020-9

PLoS One. 2021 Mar 24;16(3):e0248902. doi: 10.1371/journal.pone.0248902. eCollection 2021.

ABSTRACT

BACKGROUND: Radiologic evidence of air trapping (AT) on expiratory computed tomography (CT) scans is associated with early pulmonary dysfunction in patients with cystic fibrosis (CF). However, standard techniques for quantitative assessment of AT are highly variable, resulting in limited efficacy for monitoring disease progression.

OBJECTIVE: To investigate the effectiveness of a convolutional neural network (CNN) model for quantifying and monitoring AT, and to compare it with other quantitative AT measures obtained from threshold-based techniques.

MATERIALS AND METHODS: Paired volumetric whole lung inspiratory and expiratory CT scans were obtained at four time points (0, 3, 12 and 24 months) on 36 subjects with mild CF lung disease. A densely connected CNN (DN) was trained using AT segmentation maps generated from a personalized threshold-based method (PTM). Quantitative AT (QAT) values, presented as the relative volume of AT over the lungs, from the DN approach were compared to QAT values from the PTM method. Radiographic assessment, spirometric measures, and clinical scores were correlated to the DN QAT values using a linear mixed effects model.

RESULTS: QAT values from the DN were found to increase from 8.65% ± 1.38% to 21.38% ± 1.82%, respectively, over a two-year period. Comparison of CNN model results to intensity-based measures demonstrated a systematic drop in the Dice coefficient over time (decreased from 0.86 ± 0.03 to 0.45 ± 0.04). The trends observed in DN QAT values were consistent with clinical scores for AT, bronchiectasis, and mucus plugging. In addition, the DN approach was found to be less susceptible to variations in expiratory deflation levels than the threshold-based approach.

CONCLUSION: The CNN model effectively delineated AT on expiratory CT scans, which provides an automated and objective approach for assessing and monitoring AT in CF patients.

PMID:33760861 | DOI:10.1371/journal.pone.0248902

Scand J Immunol. 2021 Mar 24:e13040. doi: 10.1111/sji.13040. Online ahead of print.

ABSTRACT

Cystic Fibrosis (CF) is primarily a progressive lung disease, characterised by chronic pulmonary infections with opportunistic pathogens. Such infections typically commence early in life, producing an inflammatory response marked by IL-8 chemokine production and neutrophilic infiltration, major contributory factors in CF progression. Studying this inflammation, especially early in life, is critical for developing new strategies for preventing or slowing disruption to the structural integrity of the CF airways. However, evaluating the immune responses of bronchoalveolar lavage (BAL) cells from children with CF faces technical challenges, including contamination carried from the lung due to pre-existing infections and low cell number availability. Here we describe a technique for preparing BAL cells from young children with CF and using those cells in a bacterial stimulation assay. Initial antibiotic treatment proved essential for preventing resident bacteria from overgrowing BAL cell cultures, or non-specifically activating the cells. ACTB, identified as an optimal reference gene, was validated for accurate analysis of gene expression in these cells. Pseudomonas aeruginosa and Staphylococcus aureus were used as bacterial stimulants to evaluate the immune response of BAL cells from young children with CF. Addition of gentamicin prevented bacterial overgrowth, although if added after 3 hours of culture an extremely variable response resulted, with the bacteria causing a suppressive effect in some cultures. Addition of gentamicin after 1 hour of culture completely prevented this suppressive effect. This technique was then able to reproducibly measure the IL-8 response to stimulation with S. aureus and P. aeruginosa, including co-stimulation with both bacteria.

PMID:33759233 | DOI:10.1111/sji.13040