Rationale:Knowledge and awareness of COVID-19 likely results in better compliance with the guidelines set forth by local governments and may help prevent community spread of the disease. We designed a population-based survey to estimate the difference in knowledge among different groups of individuals based on sociodemographic diversities. The secondary objective was to identify significant determinants of knowledge on COVID-19. Methods: The survey questionnaire was built in Redcap. Knowledge-related questions were based on 34 metrics, including risk factors for severe infection, disease spread, prevention, treatment, and general information. Most of the questions were dichotomous ('Yes' or 'No' response). We used social media platforms, Studyfinder, and Researchmatch to send the survey link. Five sociodemographic determinants were considered potential predictors of knowledge, including age, race, education level, gender, and Healthcare Worker. Participants were also asked about their preferred source of information on COVID-19. The data was collected between June to November 2020. The 'Factor analysis' function in 'SPSS' was used to convert the 34-knowledge metrics into a single standardized scale of '0-10' for further analyses. Generalized Linear Model was built to measure the degree of association among the predictors and the knowledge score, based on 'model effect'. We further used the Machine learning tool 'Neural network' to generate a rank list of the knowledge determinants. Results: 1139 participants (male: female = 1:3) from all 50 US states participated in the survey. The generalized linear model demonstrated that the chosen determinants could precisely predict the knowledge score (χ2=93.68,p<0.001). All predictors, except healthcare workers, had significant associations with the knowledge score. Race had the highest association followed by Education, Gender, and Age (χ2=69.29,p<0.001;χ2=15.35,p<0.001;χ2=12.34,p=0.002 and χ2=4.04,p=0.044, respectively). Neural network reproduced the exact rank list with the normalized importance for Race, Education, Gender, and Age, which were 100%, 24.6%, 20%, 15.8%, respectively. Participants belonging to the 'White' race had a significantly higher score (7.71±1.13) compared to the 'Black' race (6.77±1.69) (p<0.001), while 'Female' participants performed better (7.60±1.39) compared to 'Male' (7.20±1.61) (p<0.001). Younger participants (18-44 years) had statistically significantly lower knowledge compared to older age groups (>60years) (p<0.05). Among available sources of information on COVID-19, 'City/State websites' was the most popular (67.9% favored 'Yes' vs. 'No'), followed closely by 'Television' (67.8%) and 'CDC website' (62.2%). Conclusions: 'Race' was the strongest sociodemographic predictor of COVID-related knowledge, and white, older, female participants with higher education (Masters/Ph.D.) demonstrated better knowledge than the rest of the population.

Background: Sociodemographic factors such as age, race, education, family income, and sex have been reported to influence COVID-related perceptions, reflected by knowledge, stress, and preventive behavior. We conducted a US-based survey to estimate the difference in COVID-related perceptions among diverse sociodemographic groups and the influence of sociodemographic heterogeneity on COVID-related perceptions. Methods: The survey enquired about sociodemographic parameters and relevant information to measure knowledge, stress, and preventive behavior. COVID-perception scores among sociodemographic subgroups were compared with ANOVA (Bonferroni). The general linear model (GLM) was used to estimate the association among sociodemographic factors and COVID-related perceptions. Results: Females (75%) and White participants (78%) were the predominant (N = 3734). Females, White participants, wealthy, and educated participants demonstrated better knowledge, while participants of minority races, younger ages, low incomes, and females experienced high stress. Females, African-Americans, and educated participants better adopted preventive behaviors. Race, family income, and sex were the highest contributors to the predictive model. Sociodemographic determinants had statistically significant associations with knowledge (F-score = 7.72, p < 0.001; foremost predictor: race), stress (F-score = 16.46, p < 0.001; foremost predictor: income), and preventive behavior (GLM: F-score = 7.72, p < 0.001, foremost predictor: sex). Conclusion: Sociodemographic heterogeneity significantly influenced COVID-related perceptions, while race, family income, and sex were the strongest determinants of COVID-related perceptions.

Background: Cystic Fibrosis (CF) is the most common life limiting genetic disorder, characterized by chronic respiratory failure secondary to inflammation and chronic bacterial lung infection. Pseudomonas aeruginosa lung infection is associated with more severe lung disease and rapid progression of respiratory failure when compared to Staphylococcus aureus infection. We hypothesized that a specific signature of epigenetic factors targeting specific gene transcripts contributes to the increased morbidity seen in CF patients with chronic Pseudomonas infection. Methods: We collected exhaled breath condensate (EBC) from 27 subjects and evaluated miRNA signatures in these samples using commercial PCR array. We identified predicted mRNA targets and associated signaling pathways using Ingenuity Pathway Analysis. Results: We found 11 differentially expressed miRNAs in EBC of patients infected with Pseudomonas aeruginosa compared to EBC from CF patients who were not chronically infected with Pseudomonas aeruginosa (p < 0.05). Six of these miRNAs (hsa-miRNA-1247, hsa-miRNA-1276, hsa-miRNA-449c, hsa-miRNA-3170, hsa-miRNA-432-5p and hsa-miR-548) were significantly different in the CF Pseudomonas positive group when compared to both the CF Pseudomonas negative group and healthy control group. Ingenuity pathway analysis (IPA) revealed organismal injury and abnormalities, reproductive system disease and cancer as the top diseases and bio functions associated with these miRNAs. IPA also detected RELA, JUN, TNF, IL-10, CTNNB1, IL-13, SERPINB8, CALM1, STARD3NL, SFI1, CD55, RPS6KA4, TTC36 and HIST1H3D as the top target genes for these miRNAs. Conclusion: Our study identified 6 miRNAs as epigenetic factors specifically associated with chronic Pseudomonas infection in patients with CF.

In this study, we explore palivizumab's potential benefits related to longer-term outcomes (lung function at age 7, first acquisition of Pseudomonas, and hospitalizations) in children with CF. BACKGROUND:The American Academy of Pediatrics does not recommend routine use of palivizumab prophylaxis for infants with cystic fibrosis (CF) but recommends consideration in infants with clinical evidence of chronic lung disease or nutritional compromise. However, the beneficial impact of palivizumab on longer-term outcomes is uncertain.METHODS:We used Cystic Fibrosis Foundation Patient Registry data to assess the association of receiving palivizumab during the first 2 years of life with longer-term outcomes, including lung function at 7 years old, time to first positive Pseudomonas respiratory culture, and pulmonary-related hospitalizations during the first 7 years of life. Eligible infants were born from 2008 to 2015 and diagnosed with CF during the first 6 months of life. Demographic and clinical confounders of association between palivizumab receipt and outcomes were explored. We created propensity scores to adjust for potential confounding by indication (ie, sicker infants were more likely to receive palivizumab). For each outcome, we performed regression analyses adjusted by propensity scores.RESULTS:The sample included 4267 infants; 1588 (37%) received palivizumab. Mean percent forced expiratory volume in 1 second predicted at 7 years old was similar among those who did (98.2; 95% confidence interval: 96.9-99.5) and did not (97.3; 95% confidence interval: 96.1-98.5) received palivizumab, adjusting for propensity scores. Time to first positive Pseudomonas aeruginosa culture and annual risk of hospitalization were similar among those who did and did not receive palivizumab.CONCLUSIONS:At the population level, palivizumab receipt was not associated with improved longer-term outcomes in children with CF.

Rationale: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence. Objectives: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence. Methods: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double‐blind, randomized, placebo‐controlled, 18‐month trial in children with CF, 6 months to 18 years of age, with early Pa. Azithromycin or placebo was given 3× weekly with standardized TIS. Measurements and Main Results: The primary endpoint was the time to pulmonary exacerbation requiring antibiotics and the secondary endpoint was the time to Pa recurrence, in addition to other clinical and safety outcomes. A total of 221 participants (111 placebo, 110 azithromycin) out of a planned 274 were enrolled. Enrollment was stopped early by the NHLBI because the trial had reached the prespecified interim boundary for efficacy. The risk of pulmonary exacerbation was reduced by 44% in the azithromycin group as compared with the placebo group (hazard ratio, 0.56; 95% confidence interval, 0.37‐0.83; P = 0.004). Weight increased by 1.27 kg in the azithromycin group compared with the placebo group (95% confidence interval, 0.01‐2.52; P = 0.046). No significant differences were seen in microbiological or other clinical or safety endpoints. Conclusions: Azithromycin was associated with a significant reduction in the risk of pulmonary exacerbation and a sustained improvement in weight, but had no impact on microbiological outcomes in children with early Pa. Clinical trial registered with clinicaltrials.gov (NCT02054156).

Cystic fibrosis is the most common life-limiting genetic condition in Caucasians caused by Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene mutations. Sweat chloride is the current gold standard for diagnosis where values >60 mmol/L are diagnostic and values >30 mmol/L are indeterminate. There is limited literature on the effect of medications on the sweat chloride values. We report a case of topiramate being responsible for false-positive testing which resulted in overutilisation of medical resources and psychosocial stress on the family. Topiramate should be considered during the interpretation of the gold standard testing as one of the cause of false-positive sweat tests.

Rationale: Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant antioxidant imbalance and oxidative stress. Objectives: Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidative stress, and clinical outcomes. Methods: In this investigator-initiated, multicenter, randomized, double-blind, controlled trial, 73 pancreatic-insufficient subjects with CF 10 years of age and older with an FEVI between 40% and 100% predicted were randomized to 16 weeks of an antioxidant-enriched multivitamin or control multivitamin without antioxidant enrichment Endpoints included systemic antioxidant concentrations, markers of inflammation and oxidative stress, clinical outcomes (pulmonary exacerbations, anthropometric measures, pulmonary function), safety, and tolerability. Measurements and Main Results: Change in sputum myeloperoxidase concentration over 16 weeks, the primary efficacy endpoint, was not significantly different between the treated and control groups. Systemic antioxidant ((beta-carotene, coenzyme Q10, gamma-tocopherol, and lutein) concentrations significantly increased in the antioxidant-treated group (P < 0.001 for each), whereas circulating calprotectin and myeloperoxidase decreased in the treated group compared with the control group at Week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio, 0.50; P = 0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. Conclusions: Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation.

Einleitung: Von einer exokrinen Pankreasinsuffizienz sind mehr als 85% der Patienten mit Mukoviszidose betroffen. NM-BL ist eine neuartige Lipase mikrobiellen Ursprungs in einer flüssigen Formulierung zur Behandlung der exokrinen Pankreasinsuffizienz. Die klinische Wirksamkeit einer Lipase wird mittels des Koeffizienten für die Fettabsorption (CFA) als Surrogatparameter belegt. Für Patienten mit schwerwiegender exokriner Pankreasinsuffizienz und einem CFA < 40% sollte dieser mindestens um 30% verbessert werden.

Objective To evaluate the safety and efficacy of a novel microbial lipase (NM-BL) in a liquid formulation for the treatment of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis (CF) in a phase IIa proof-of-concept study.Study design We conducted a double-blind, randomized, placebo controlled crossover study in patients with cystic fibrosis and exocrine pancreatic insufficiency. Adolescent and adult patients with CF were randomized to receive NM-BL or placebo for 1 week as replacement for their usual pancreatic enzyme formulation. They were subsequently crossed-over to the alternate study treatment. The coefficient of fat absorption was evaluated as the primary endpoint. Symptoms and adverse events were evaluated as secondary endpoints.Results A total of 35 patients were randomized into the study and 22 patients completed both treatment periods. During treatment with NM-BL, the coefficient of fat absorption was significantly greater (72.7%) compared with placebo (53.8%) with a difference between groups of 18.8% (P <.001). Subjective assessment of stool fat and stool consistency also improved under treatment with NM-BL. Adverse events were mostly gastrointestinal in nature and were more common in the group receiving NM-BL.Conclusions Currently available pancreatic enzyme products are limited because of the lack of liquid formulations and being largely porcine based. The novel microbial lipase NM-BL was safe and effective in this short term trial. The trial provided clinical proof-of-concept for this novel microbial lipase as a treatment for EPI in CF. A larger phase 2 dose ranging trial is warranted.

BACKGROUND:Vitamin D deficiency is common in CF. Whether vitamin D affects pulmonary function in CF is unknown.METHODS:Data were abstracted from clinically stable CF patients who had pulmonary function studies and serum 25-hydroxyvitamin D [25(OH)D, ng/ml] levels drawn within 2 months of each other. Findings were adjusted for multiple variables known to affect pulmonary function in CF.RESULTS:Enrollees totaled 597. Overall mean 25(OH)D level was 29.6±12.8 ng/ml (SD). Serum 25(OH)D levels showed a significant correlation with forced expiratory volume in 1s (FEV1) % predicted (r=0.20, p<0.0001) and forced vital capacity % predicted (r=0.13, p=0.0019). Multivariate analysis revealed that serum 25(OH)D remained an independent predictor of FEV1 % predicted even after controlling for multiple other factors known to affect CF lung function.CONCLUSIONS:Serum 25(OH)D levels are significantly associated with pulmonary function in CF. Further study is required to determine whether this association is causal.