Genet Mol Biol. 2021 Dec 6;45(1):e20200275. doi: 10.1590/1678-4685-GMB-2020-0275. eCollection 2021.

ABSTRACT

This is a descriptive cross-sectional study that aims to determine the distribution of the CFTR causing variant in a group of patients at a cystic fibrosis (CF) center in southern Brazil, as well as to describe causing variants that are treatable with mutation-specific drugs. Ninety-two patients from a CF reference center were assessed in this research, all of them with a clinical diagnosis of CF and both alleles identified with pathogenic variants. The most prevalent causing variants were F508del, R1162X, G542X, and N1303K. As for patients with a mutation-specific drug indication, 69.6 % were candidates for the use of Elexacaftor/Tezacaftor/Ivacaftor (Trikafta®), 44.6 % for the use of Tezacaftor/Ivacaftor (Symdeko®), and 35.9 % for the use of Lumacaftor/Ivacaftor (Orkambi®). For the use of Ivacaftor (Kalydeco®), only two patients (2.2 %) were candidates following the Brazilian agency approval. According to the FDA, 10 patients would be candidates for Ivacaftor (10.9 %). Causing variants of classes I and II, which are related to a major severity of the illness, were identified in 135 of 184 alleles (73.3 %). In this study, more than 2/3 of the patients were candidates for the use of CFTR modulators therapy.

PMID:34874053 | DOI:10.1590/1678-4685-GMB-2020-0275

J Pediatr. 2021 Dec 3:S0022-3476(21)01157-4. doi: 10.1016/j.jpeds.2021.11.059. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare performance of weight-for-length (WFL) and body mass index (BMI) as estimators of undernutrition in children with cystic fibrosis (CF).

STUDY DESIGN: We analysed pediatric anthropometric data from the Cystic Fibrosis Foundation Patient Registry. Undernutrition was defined by weight-for-length z-score (WFLZ) or body mass index z-score (BMIZ) ≤-1 (15th-percentile). Group1, reference group, consisted of subjects with both BMIZ and WFLZ >-1; Group2: BMIZ ≤-1 and WFLZ >-1; Group3: BMIZ >-1 and WFLZ ≤-1 and Group4: BMIZ and WFLZ ≤-1. Group differences in length-for-age-Z (LAZ) across age 2-24mo were tested using generalized estimating equations. The association of Group at age 2mo with BMIZ<-1 at age 6y was tested using logistic regression adjusted for demographic and disease characteristics.

RESULTS: Overall, 163,482 anthropometric measurements were available from 12,640 individuals, of whom 16.8% were discordant for undernutrition status at age 2 months. Discordance (1.5-10%) was less common with increasing age. LAZ was lower in Group2 than Group1 and Group3 between birth and 24 months (p<0.05). Odds of WFLZ-defined undernourished at 2 months were lower for shorter individuals (OR 1.5, CI 1.4-1.6, P < .001). Undernutrition risk at age 6 years was greater for Group2 vs Group3 (OR 1.9 vs 1.0, p<0.001).

CONCLUSIONS: Infants with CF classified as undernourished by BMIZ, but not WFLZ, had greater risk of undernourished status later in childhood. Infants with low BMIZ but normal WFLZ tended to be shorter, suggesting BMIZ may better capture undernourished status than WFLZ in shorter infants.

PMID:34871592 | DOI:10.1016/j.jpeds.2021.11.059

World Allergy Organ J. 2021 Nov 19;14(11):100606. doi: 10.1016/j.waojou.2021.100606. eCollection 2021 Nov.

ABSTRACT

INTRODUCTION: There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients.

METHODS: Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR.

RESULTS: 540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values.

CONCLUSIONS: The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem.

PMID:34871335 | PMC:PMC8609160 | DOI:10.1016/j.waojou.2021.100606

Elife. 2021 Dec 6;10:e74693. doi: 10.7554/eLife.74693. Online ahead of print.

ABSTRACT

The phosphorylation-activated anion channel CFTR is gated by an ATP hydrolysis cycle at its two cytosolic nucleotide binding domains, and is essential for epithelial salt-water transport. A large number of CFTR mutations cause cystic fibrosis. Since recent breakthrough in targeted pharmacotherapy, CFTR mutants with impaired gating are candidates for stimulation by potentiator drugs. Thus, understanding the molecular pathology of individual mutations has become important. The relatively common R117H mutation affects an extracellular loop, but nevertheless causes a strong gating defect. Here we identify a hydrogen bond between the side chain of arginine 117 and the backbone carbonyl group of glutamate 1124 in the cryo-electronmicroscopic structure of phosphorylated, ATP-bound CFTR. We address the functional relevance of that interaction for CFTR gating using macroscopic and microscopic inside-out patch-clamp recordings. Employing thermodynamic double-mutant cycles, we systematically track gating-state dependent changes in the strength of the R117-E1124 interaction. We find that the H-bond is formed only in the open state, but neither in the short-lived "flickery" nor in the long-lived 'interburst' closed state. Loss of this H-bond explains the strong gating phenotype of the R117H mutant, including robustly shortened burst durations and strongly reduced intraburst open probability. The findings may help targeted potentiator design.

PMID:34870594 | DOI:10.7554/eLife.74693

Front Bioeng Biotechnol. 2021 Nov 19;9:775309. doi: 10.3389/fbioe.2021.775309. eCollection 2021.

ABSTRACT

During recent years, clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technologies have been noticed as a rapidly evolving tool to deliver a possibility for modifying target sequence expression and function. The CRISPR/Cas9 tool is currently being used to treat a myriad of human disorders, ranging from genetic diseases and infections to cancers. Preliminary reports have shown that CRISPR technology could result in valued consequences for the treatment of Duchenne muscular dystrophy (DMD), cystic fibrosis (CF), β-thalassemia, Huntington's diseases (HD), etc. Nonetheless, high rates of off-target effects may hinder its application in clinics. Thereby, recent studies have focused on the finding of the novel strategies to ameliorate these off-target effects and thereby lead to a high rate of fidelity and accuracy in human, animals, prokaryotes, and also plants. Meanwhile, there is clear evidence indicating that the design of the specific sgRNA with high efficiency is of paramount importance. Correspondingly, elucidation of the principal parameters that contributed to determining the sgRNA efficiencies is a prerequisite. Herein, we will deliver an overview regarding the therapeutic application of CRISPR technology to treat human disorders. More importantly, we will discuss the potent influential parameters (e.g., sgRNA structure and feature) implicated in affecting the sgRNA efficacy in CRISPR/Cas9 technology, with special concentration on human and animal studies.

PMID:34869290 | PMC:PMC8640246 | DOI:10.3389/fbioe.2021.775309

Front Pediatr. 2021 Nov 15;9:744705. doi: 10.3389/fped.2021.744705. eCollection 2021.

ABSTRACT

Background: The combination of the CFTR corrector lumacaftor (LUM) and potentiator ivacaftor (IVA) has been labeled in France since 2015 for F508del homozygote cystic fibrosis (CF) patients over 12 years. In this real-life study, we aimed (i) to compare the changes in lung function, clinical (e.g., body mass index and pulmonary exacerbations) and radiological parameters, and in sweat chloride concentration before and after initiation of LUM/IVA treatment; (ii) to identify factors associated with response to treatment; and (iii) to assess the tolerance to treatment. Materials and Methods: In this tri-center, non-interventional, and observational cohort study, children (12-18 years old) were assessed prospectively during the 2 years of therapy, and retrospectively during the 2 years preceding treatment. Data collected and analyzed for the study were exclusively extracted from the medical electronic system records of the patients. Results: Forty adolescents aged 12.0-17.4 years at LUM/IVA initiation were included. The lung function decreased significantly during and prior to treatment and increased after LUM/IVA initiation, becoming significant after 2 years of treatment. LUM/IVA significantly improved the BMI Z-score and sweat chloride concentration. By contrast, there was no significant change in exacerbation rates, antibiotic use, or CT scan scores. Age at LUM/IVA initiation was lower in good responders and associated with greater ppFEV1 change during the 2 years of treatment. LUM/IVA was well-tolerated. Conclusion: In F508del homozygote adolescents, real-life long-term LUM/IVA improved the ppFEV1 trajectory, particularly in the youngest patients, nutritional status, and sweat chloride concentration but not exacerbation rates or radiological scores. LUM/IVA was generally well-tolerated and safe.

PMID:34869102 | PMC:PMC8634876 | DOI:10.3389/fped.2021.744705

J Clin Transl Endocrinol. 2021 Nov 17;26:100276. doi: 10.1016/j.jcte.2021.100276. eCollection 2021 Dec.

ABSTRACT

The prevalence of obesity in patients with cystic fibrosis (CF) is increasing and around one-third of adults with CF are now overweight or obese. The causes of excess weight gain in CF are likely multifactorial, including: adherence to the high-fat legacy diet, reduced exercise tolerance, therapeutic advances, and general population trends. Increased weight has generally been considered favorable in CF, correlating with improved pulmonary function and survival. While the optimal BMI for overall health in CF is unknown, most studies demonstrate minimal improvement in pulmonary function when BMI exceeds 30 kg/m2. Dyslipidemia and cardiovascular disease are important co-morbidities of obesity in the general population, but are uncommon in CF. In people with CF, obesity is associated with hypertension and higher cholesterol levels. With longer life expectancy and rising obesity rates, there may be an increase in cardiovascular disease among people with CF in coming years. Overweight CF patients are more likely to be insulin resistant, taking on features of type 2 diabetes. Treating obesity in people with CF requires carefully weighing the metabolic risks of overnutrition with the impact of low or falling BMI on lung function. This article describes current knowledge on the epidemiology, causes, consequence, and treatment of obesity in people with CF.

PMID:34868883 | PMC:PMC8626670 | DOI:10.1016/j.jcte.2021.100276

J Clin Transl Endocrinol. 2021 Nov 16;26:100275. doi: 10.1016/j.jcte.2021.100275. eCollection 2021 Dec.

ABSTRACT

Oral glucose tolerance testing (OGTT) is the primary method to screen for and diagnose cystic fibrosis-related diabetes (CFRD). Diagnostic thresholds as currently defined are based on microvascular complications seen in type 2 diabetes. Abnormal glucose tolerance (AGT) refers to OGTT glucose elevations outside the normal range and encompasses both impaired and indeterminate glucose tolerance. Current guidelines define impaired glucose tolerance (IGT) as a 2-hour glucose of 140-199 mg/dL (7.8-11 mmol/L) and indeterminate glucose tolerance (INDET) as any mid-OGTT glucose ≥ 200 mg/dL (11.1 mmol/L) with a normal fasting and 2 h glucose. There is growing evidence that AGT also has associations with CF-centered outcomes including pulmonary decline, hospitalizations, and weight loss. Here we aim to review the historical emergence of glucose tolerance testing, review relevance to risk stratification for CFRD, discuss alternate cutoffs for identifying AGT earlier, and highlight the need for larger, future studies to inform our understanding of the implications of IGT and INDET on CF health.

PMID:34868882 | PMC:PMC8626567 | DOI:10.1016/j.jcte.2021.100275

Front Genet. 2021 Nov 12;12:739311. doi: 10.3389/fgene.2021.739311. eCollection 2021.

ABSTRACT

Altered microRNA expression patterns in bronchial brushings from people with versus without cystic fibrosis (CF) relate to functional changes and disease pathophysiology. The expression of microRNAs encoded on the X chromosome is also altered in peripheral blood monocytes of p. Phe508del homozygous versus non-CF individuals. Here we investigate whether levels of the top seven X-linked microRNAs (miR-224-5p, miR-452-5p, miR-450b-5p, miR-542-3p, miR-450a-5p, miR-424-5p, and miR-545-5p) that are significantly increased over 1.5 fold in CF versus non-CF monocytes correlate with lung function. CD14+ monocytes were isolated from males and females with (n = 12) and without cystic fibrosis (n = 12) and examined for the expression of X-linked microRNAs by qRT-PCR array. MicroRNA target mRNA levels were quantified using qRT-PCR. Clinical correlations with lung function data were analysed in the CF cohort. Increasing levels of miR-545-5p correlated moderately with FEV1% predicted (r = -0.4553, p > 0.05) and strongly with exacerbation rate (r = 0.5858, p = 0.0483). miR-224-5p levels were significantly higher in the severe (FEV1 <40%) versus mild (FEV1 ≥80%, p = 0.0377) or moderate (FEV1 40-79%, p = 0.0350) groups. MiR-224-5p expression inversely correlated with lung function (FEV1%: r = -0.5944, p = 0.0457) and positively correlated with exacerbation rates (r = 0.6139, p = 0.0370). These data show that peripheral blood monocyte miR-545-5p and miR-224-5p levels correlate with exacerbation rate, whilst miR-224-5p levels also correlate with lung function in cystic fibrosis.

PMID:34868211 | PMC:PMC8633565 | DOI:10.3389/fgene.2021.739311

Front Microbiol. 2021 Nov 19;12:747834. doi: 10.3389/fmicb.2021.747834. eCollection 2021.

ABSTRACT

Pseudomonas aeruginosa is the most prevalent bacterial species that contribute to cystic fibrosis (CF) respiratory failure. The impaired function of CF transmembrane conductance regulator leads to abnormal epithelial Cl-/HCO3 - transport and acidification of airway surface liquid. However, it remains unclear why the CF lung is most commonly infected by Pseudomonas aeruginosa versus other pathogens. We carried out studies to investigate if lower pH helps Pseudomonas aeruginosa adapt and thrive in the CF-like acidic lung environment. Our results revealed that Pseudomonas aeruginosa generally forms more biofilm, induces antibiotic resistance faster in acidic conditions, and can be reversed by returning the acidic environment to physiologically neutral conditions. Pseudomonas aeruginosa appears to be highly adaptive to the CF-like acidic pH environment. By studying the effects of an acidic environment on bacterial response, we may provide a new therapeutic option in preventing chronic Pseudomonas aeruginosa infection and colonization.

PMID:34867864 | PMC:PMC8640179 | DOI:10.3389/fmicb.2021.747834

Front Pharmacol. 2021 Nov 4;12:794854. doi: 10.3389/fphar.2021.794854. eCollection 2021.

NO ABSTRACT

PMID:34867428 | PMC:PMC8632627 | DOI:10.3389/fphar.2021.794854

Front Pharmacol. 2021 Nov 11;12:773241. doi: 10.3389/fphar.2021.773241. eCollection 2021.

ABSTRACT

Background: The exacerbation of non-cystic fibrosis bronchiectasis (NCFB) may lead to poor prognosis. The objective of this study was to retrospectively analyze the clinical efficacy and safety of endobronchial therapy with gentamicin and dexamethasone after airway clearance by bronchoscopy in the exacerbation of NCFB. Methods: We retrospectively reviewed 2,156 patients with NCFB between January 2015 and June 2016 and 367 consecutive patients with exacerbation of bronchiectasis who had complete data and underwent airway clearance (AC) by bronchoscopy. The final cohort included 181 cases of intratracheal instillation with gentamicin and dexamethasone after AC (a group with airway drugs named the drug group) and 186 cases of AC only (a group without airway drugs named the control group). The last follow-up was on June 30, 2017. Results: The total cough score and the total symptom score in the drug group were improved compared to those in the control group during 3 months after discharge (p < 0.001). Re-examination of chest HRCT within 4-6 months after discharge revealed that the improvements of peribronchial thickening, the extent of mucous plugging, and the Bhalla score were all significantly improved in the drug group. Moreover, the re-exacerbations in the drug group were significantly decreased within 1 year after discharge. Univariate analysis showed a highly significant prolongation of the time to first re-exacerbation in bronchiectasis due to treatment with airway drugs compared with that of the control group. Multivariate Cox regression analysis showed that the risk of first re-exacerbation in the drug group decreased by 29.7% compared with that of the control group. Conclusion: Endobronchial therapy with gentamicin and dexamethasone after AC by bronchoscopy is a safe and effective method for treating NCFB.

PMID:34867404 | PMC:PMC8632621 | DOI:10.3389/fphar.2021.773241

Arch Bronconeumol. 2021 Dec;57(12):739-740. doi: 10.1016/j.arbr.2021.04.017. Epub 2021 Dec 1.

NO ABSTRACT

PMID:34866750 | PMC:PMC8634802 | DOI:10.1016/j.arbr.2021.04.017

J Cyst Fibros. 2021 Dec 2:S1569-1993(21)02158-5. doi: 10.1016/j.jcf.2021.11.017. Online ahead of print.

NO ABSTRACT

PMID:34866012 | DOI:10.1016/j.jcf.2021.11.017

Respir Med. 2021 Nov 23;191:106687. doi: 10.1016/j.rmed.2021.106687. Online ahead of print.

ABSTRACT

BACKGROUND: People with cystic fibrosis (PWCF) suffer from acute unpredictable reductions in pulmonary function associated with a pulmonary exacerbation (PEx) that may require hospitalization. PEx symptoms vary between PWCF without universal diagnostic criteria for diagnosis and response to treatment.

RESEARCH QUESTION: We characterized sweat metabolomes before and after intravenous (IV) antibiotics in PWCF hospitalized for PEx to determine feasibility and define biological alterations by IV antibiotics for PEx.

STUDY DESIGN AND METHODS: PWCF with PEx requiring hospitalization for IV antibiotics were recruited from clinic. Sweat samples were collected using the Macroduct® Sweat Collection System at admission prior to initiation of IV antibiotics and after completion prior to discharge. Samples were analyzed for metabolite changes using ultra-high-performance liquid chromatography/tandem accurate mass spectrometry.

RESULTS: Twenty-six of 29 hospitalized PWCF completed the entire study. A total of 326 compounds of known identity were detected in sweat samples. Of detected metabolites, 147 were significantly different between pre-initiation and post-completion of IV antibiotics for PEx (average treatment 14 days). Global sweat metabolomes changed from before and after IV antibiotic treatment. We discovered specific metabolite profiles predictive of PEx status as well as enriched biologic pathways associated with PEx. However, metabolomic changes were similar in PWCF who failed to return to baseline pulmonary function and those who did not.

INTERPRETATION: Our findings demonstrate the feasibility of non-invasive sweat metabolomic profiling in PWCF and the potential for sweat metabolomics as a prospective diagnostic and research tool to further advance our understanding of PEx in PWCF.

PMID:34864373 | DOI:10.1016/j.rmed.2021.106687

Res Involv Engagem. 2021 Dec 4;7(1):86. doi: 10.1186/s40900-021-00328-4.

ABSTRACT

BACKGROUND: Patient-centered outcomes research (PCOR) emphasizes patient-generated research priorities and outcomes, and engages patients throughout every stage of the research process. In the cystic fibrosis (CF) community, patients frequently provide input into research studies, but rarely are integrated onto research teams. Therefore, we developed and evaluated a virtual pilot PCOR training program to build PCOR capacity in the CF community (patients, caregivers, researchers, nonprofit stakeholders and providers). We aimed to show changes among participants' perceived PCOR knowledge (a.k.a PCOR knowledge), confidence in engaging stakeholders, and post-training session satisfaction.

METHODS: Guided by a prior CF community educational needs assessment, our researcher and patient-partner team co-developed a four-part virtual online training program. We structured the program towards two learner groups: patients/caregivers and researchers/providers. We evaluated participants' PCOR knowledge, confidence in engaging stakeholders, and session satisfaction by administering 5-point Likert participant surveys. We tested for significant differences between median ratings pre- and post-training.

RESULTS: A total of 28 patients/caregivers, and 31 researchers/providers participated. For both learner groups, we found the training resulted in significantly higher PCOR knowledge scores regarding "levels of engagement" (p = .008). For the patient/caregiver group, training significantly increased their PCOR knowledge about the barriers/enablers to doing PCOR (p = .017), effective PCOR team elements (p = .039), active participation (p = .012), and identifying solutions for successful PCOR teams (p = .021). For the researcher/healthcare provider group, training significantly increased participants' ability to describe PCOR core principles (p = .016), identify patient-partners (p = .039), formulate research from patient-driven priorities (p = .039), and describe engagement in research grants (p = .006). No learner group had significant changes in their confidence score. Most participants were either "satisfied" or "very satisfied" with the training program.

CONCLUSIONS: Overall, our virtual pilot PCOR training program was well received by patients, caregivers, researchers and providers in the CF community. Participants significantly improved their perceived knowledge with core PCOR learning items. Trial registration Retrospectively registered at clinicaltrials.gov (NCT04999865).

PMID:34863273 | DOI:10.1186/s40900-021-00328-4

Clin Med (Lond). 2021 Nov;21(6):e571-e577. doi: 10.7861/clinmed.2021-0651.

ABSTRACT

Bronchiectasis is a heterogeneous and increasingly prevalent chronic pulmonary disease that is associated with significant morbidity. In this review, we outline how patients with bronchiectasis may present clinically and describe an approach to its diagnosis, including how to identify an underlying aetiology. We discuss the important considerations when treating either acute exacerbations or stable disease and provide an overview of the role of long-term antimicrobials, airway clearance methods and other supportive management.

PMID:34862215 | DOI:10.7861/clinmed.2021-0651

J Cyst Fibros. 2021 Nov 30:S1569-1993(21)02153-6. doi: 10.1016/j.jcf.2021.11.012. Online ahead of print.

ABSTRACT

BACKGROUND: Though weight gain has been reported in some clinical trials of CFTR modulators, the effect of elexacaftor-tezacaftor-ivacaftor on body weight, body mass index (BMI), blood pressure, lipids and glycemic control in the real-world setting remains incompletely described.

METHODS: We performed a single-center, retrospective, observational analysis of the effect of elexacaftor-tezacaftor-ivacaftor on body weight and cardiometabolic parameters in 134 adult CF patients of the Washington University Adult Cystic Fibrosis Center. Body weight, BMI, and blood pressure were extracted from outpatient clinic visits for the year preceding and the period following the initiation of elexacaftor-tezacaftor-ivacaftor. Other metabolic parameters were extracted at baseline and at latest available follow-up.

RESULTS: A mean of 12.2 months of follow-up data was available for analysis. The mean rate of change in BMI was 1.47 kg/m2/yr (95% CI, 1.08 to 1.87) greater after initiation of elexacaftor-tezacaftor-ivacaftor. Significant increases in blood pressure were observed. In those without CFRD, random blood glucose and hemoglobin A1c were decreased after elexacaftor-tezacaftor-ivacaftor initiation. In those with CFRD, elexacaftor-tezacaftor-ivacaftor increased serum total cholesterol, HDL-cholesterol, and LDL-cholesterol.

CONCLUSIONS: In this single-center, retrospective, observational study of 134 adults with CF, initiation of elexacaftor-tezacaftor-ivacaftor was associated with increases in BMI at a mean follow up of 12.2 months. Changes in other cardiometabolic risk factors were also observed. Widespread use of elexacaftor-tezacaftor-ivacaftor may be expected to increase the incidence of overnutrition in the CF population.

PMID:34862121 | DOI:10.1016/j.jcf.2021.11.012

Pancreas. 2021 Oct 1;50(9):1305-1309. doi: 10.1097/MPA.0000000000001923.

ABSTRACT

OBJECTIVES: It is unknown to what extent coronavirus 2019 (COVID-19) may co-occur with acute pancreatitis (AP) in children and how their clinical course may differ from children with AP alone.

METHODS: An online survey was sent to pediatric gastroenterologists to report on COVID-19 and AP cases from December 11, 2020, to February 26, 2021.

RESULTS: From 72 respondents (20 countries, 5 continents), 22 cases of positive COVID-19 infection and AP were reported. Patients were predominantly White or Hispanic/Latinx (73%), female (68%), and adolescents (68%). For 86% of patients, this was their first episode of AP. Sixty-eight percent of positive COVID-19 tests were polymerase chain reaction based. There was significant morbidity; 60% required intensive care, 45% had multiorgan involvement, and 24% developed shock. Eleven percent had pancreatic necrosis. Abnormal clotting and systemic inflammatory laboratories were common (31%-92% and 93%, respectively). Median length of symptomatic pancreatitis recovery was 1.8× longer than AP without COVID-19.

CONCLUSIONS: Coronavirus 2019 infection and AP co-occur primarily in children without a prior history of pancreatitis. Given the increased need for intensive care, multiorgan involvement, and potentially higher risk for pancreatic necrosis, pediatric providers should have a high level of suspicion for AP in children with COVID-19 infection.

PMID:34860816 | DOI:10.1097/MPA.0000000000001923

Pulm Ther. 2021 Dec 3. doi: 10.1007/s41030-021-00178-1. Online ahead of print.

ABSTRACT

Mucus secretion in the lungs is a natural process that protects the airways from inhaled insoluble particle accumulation by capture and removal via the mucociliary escalator. Diseases such as cystic fibrosis (CF) and associated bronchiectasis, as well as chronic obstructive pulmonary disease (COPD), result in mucus layer thickening, associated with high viscosity in CF, which can eventually lead to complete airway obstruction. These processes severely impair the delivery of inhaled medications to obstructed regions of the lungs, resulting in poorly controlled disease with associated increased morbidity and mortality. This narrative review article focuses on the use of non-pharmacological airway clearance therapies (ACTs) that promote mechanical movement from the obstructed airway. Particular attention is given to the evolving application of oscillating positive expiratory pressure (OPEP) therapy via a variety of devices. Advice is provided as to the features that appear to be the most effective at mucus mobilization.

PMID:34860355 | DOI:10.1007/s41030-021-00178-1