Allergo J Int. 2021 Sep 28:1-9. doi: 10.1007/s40629-021-00189-z. Online ahead of print.

ABSTRACT

Peanuts are Leguminosae, commonly known as the legume or pea family, and peanut allergy is among the most common food allergies and the most common cause of fatal food reactions and anaphylaxis. The prevalence of peanut allergy increased 3.5-fold over the past two decades reaching 1.4-2% in Europe and the United States. The reasons for this increase in prevalence are likely multifaceted. Sensitization via the skin appears to be associated with the development of peanut allergy and atopic eczema in infancy is associated with a high risk of developing peanut allergy. Until recently, the only possible management strategy for peanut allergy was strict allergen avoidance and emergency treatment including adrenaline auto-injector in cases of accidental exposure and reaction. This paper discusses the various factors that impact the risks of peanut allergy and the burden of self-management on peanut-allergic children and their caregivers.

PMID:34603938 | PMC:PMC8477625 | DOI:10.1007/s40629-021-00189-z

J Cyst Fibros. 2021 Sep 30:S1569-1993(21)01420-X. doi: 10.1016/j.jcf.2021.09.015. Online ahead of print.

NO ABSTRACT

PMID:34602342 | DOI:10.1016/j.jcf.2021.09.015

Toxicol In Vitro. 2021 Sep 30:105253. doi: 10.1016/j.tiv.2021.105253. Online ahead of print.

ABSTRACT

The airway epithelium is exposed to a variety of air pollutants, which have been associated with the onset and worsening of respiratory diseases. These air pollutants can vary depending on their composition and associated chemicals, leading to different molecular interactions and biological effects. Mucociliary clearance is an important host defense mechanism against environmental air pollutants and this process is regulated by various ion transporters including the cystic fibrosis transmembrane conductance regulator (CFTR). With evidence suggesting that environmental air pollutants can lead to acquired CFTR dysfunction, it may be possible to leverage therapeutic approaches used in cystic fibrosis (CF) management. The aim of our study was to test whether environmental air pollutants tobacco smoke extract, urban particulate matter, and diesel exhaust particles lead to acquired CFTR dysfunction and whether it could be rescued with pharmacological interventions. Human airway epithelial cells (Calu-3) were exposed to air pollutant extracts for 24 h, with and without pharmacological interventions, with readouts of CFTR expression and function. We demonstrate that both tobacco smoke extract and diesel exhaust particles led to acquired CFTR dysfunction and that rescue of acquired CFTR dysfunction is possible with pharmacological interventions in diesel exhaust particle models. Our study emphasizes that CFTR function is not only important in the context of CF but may also play a role in other respiratory diseases impacted by environmental air pollutants. In addition, the pharmacological interventions approved for CF management may be more broadly leveraged for chronic respiratory disease management.

PMID:34601066 | DOI:10.1016/j.tiv.2021.105253

J Cyst Fibros. 2021 Sep 29:S1569-1993(21)01414-4. doi: 10.1016/j.jcf.2021.09.009. Online ahead of print.

NO ABSTRACT

PMID:34600843 | DOI:10.1016/j.jcf.2021.09.009

Orphanet J Rare Dis. 2021 Oct 2;16(1):409. doi: 10.1186/s13023-021-02049-z.

ABSTRACT

BACKGROUND: Specialized clinical care for cystic fibrosis (CF) in Cyprus, a small island country, has been implemented since the 1990s. However, only recently, a national CF patient registry has been established for the systematic recording of patients' data. In this study, we aim to present data on the epidemiological, genotypic and phenotypic features of CF patients in the country from the most recent data collection in 2019, with particular emphasis on notable rare or unique cases.

RESULTS: Overall, data from 52 patients are presented, 5 of whom have deceased and 13 have been lost to follow-up in previous years. The mean age at diagnosis was 7.2 ± 12.3 years, and the mean age of 34 alive patients by the end of 2019 was 22.6 ± 13.2 years. Patients most commonly presented at diagnosis with acute or persistent respiratory symptoms (46.2%), failure to thrive or malnutrition (40.4%), and dehydration or electrolyte imbalance (32.7%). Sweat chloride levels were diagnostic (above 60 mmol/L) in 81.8% of examined patients. The most common identified mutation was p.Phe508del (F508del) (45.2%), followed by p.Leu346Pro (L346P) (6.7%), a mutation detected solely in individuals of Cypriot descent. The mean BMI and FEV1 z-scores were 0.2 ± 1.3 and - 2.1 ± 1.7 across all age groups, respectively, whereas chronic Pseudomonas aeruginosa colonization was noted in 26.9% of patients. The majority of patients (74.5%) were eligible to receive at least one of the available CFTR modulator therapies. In 25% of patients we recovered rare or unique genotypic profiles, including the endemic p.Leu346Pro (L346P), the rare CFTR-dup2, the co-segregated c.4200_4201delTG/c.489 + 3A > G, and the polymorphism p.Ser877Ala.

CONCLUSIONS: CF patient registries are particularly important in small or isolated populations, such as in Cyprus, with rare or unique disease cases. Their operation is necessary for the optimization of clinical care provided to CF patients, enabling their majority to benefit from evolving advances in precision medicine.

PMID:34600583 | DOI:10.1186/s13023-021-02049-z

Eur Respir J. 2021 Oct 1;58(3):2101487. doi: 10.1183/13993003.01487-2021. Print 2021 Sep.

NO ABSTRACT

PMID:34598976 | DOI:10.1183/13993003.01487-2021

J Cyst Fibros. 2021 Sep 28:S1569-1993(21)01419-3. doi: 10.1016/j.jcf.2021.09.014. Online ahead of print.

ABSTRACT

BACKGROUND: Elexacaftor-tezacaftor-ivacaftor (ETI) improves pulmonary health and chronic rhinosinusitis (CRS) for people with cystic fibrosis (PwCF), however its impact on olfaction has not been investigated. Olfactory dysfunction impairs quality-of-life (QOL). This study evaluated the impact of ETI on multiple olfactory metrics.

METHODS: Adult PwCF/CRS with CF transmembrane conductance regulator genotype F508del/F508del or F508del/minimal function who clinically initiated ETI participated in a prospective, observational study. Endpoints included changes after 6 months of ETI in quantitative olfactory function (Smell Identification Test, SIT), olfactory QOL (Questionnaire of Olfactory Disorders, QOD) and percent olfactory cleft opacification (%OCO), representing superior nasal cavity inflammation where afferent olfactory neurons are concentrated.

RESULTS: 30 PwCF/CRS met inclusion criteria; 25 completed the study. Mean ETI adherence was 93%. At baseline, participants were hyposmic (mean SIT 31.3), had significant %OCO (mean 65.6%), yet reported non-impaired olfactory QOL (mean QOD 6.1). At follow-up, mean SIT worsened mildly (p=0.009), mean %OCO remained stable (p=0.46), and mean QOD improved modestly (p=0.008). No outcomes were impacted by prior modulator use, genotype, nasal polyps, or CF-related diabetes. Prior sinus surgery was associated with QOD improvement (p=0.04). Increased (worse) baseline QOD scores and %OCO were associated with greater improvements (p<0.003), but not SIT (p=0.44).

CONCLUSIONS: ETI was not associated with improvement in quantitative olfaction or olfactory cleft opacification after 6 months. PwCF/CRS have hyposmia but do not report impairment in olfactory QOL. Further study to investigate mechanisms explaining olfactory dysfunction and whether olfaction improves with greater duration of ETI or in younger age groups is warranted.

PMID:34598881 | DOI:10.1016/j.jcf.2021.09.014

BJOG. 2021 Oct 1. doi: 10.1111/1471-0528.16957. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare pregnancy rates and outcomes for women with cystic fibrosis in the UK with the general population and assess the effect of introduction of disease modifying treatment.

DESIGN: A population-based longitudinal study, 2003-17 SETTING: United Kingdom POPULATION: Women aged 15-44 years in the UK CF Registry compared to women in England and Wales.

METHODS: We calculated pregnancy and live birth rates for the CF and England and Wales (E&W) populations. For women with CF we compared pregnancy rates before and after ivacaftor was introduced in 2013. We further used CF registry data to assess pregnancy outcomes for mothers with CF, and to assess the relationship between maternal pre-pregnancy lung function and nutritional status and child gestational age.

MAIN OUTCOME MEASURES: Pregnancy and live birth rates; and child gestational age.

RESULTS: Of 3,831 women with CF, 661 reported 818 pregnancies. Compared E&W the pregnancy rate was 3.3 times lower in the CF population (23.5 vs. 77.7 per 1,000 women years); the live birth rate was 3.5 times lower (17.4 vs. 61.4 per 1,000 women years) with 70% of pregnancies in CF women resulting in live births; abortion rates were also lower (9% vs. 22%). Pregnancy rates increased post-ivacaftor for eligible women with CF, from 29.7 to 45.7 per 1,000 women years. There was no association between pre-pregnancy lung function/nutrition status and gestational age.

CONCLUSIONS: Pregnancy rates in women with CF are about a third of the rates in E&W with favourable outcomes, and increased for eligible women post-ivacaftor.

PMID:34597459 | DOI:10.1111/1471-0528.16957

Pediatr Int. 2021 Oct 1. doi: 10.1111/ped.15009. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a chronic disease causing recurrent respiratory tract infections. Viral respiratory tract infections are more severe in CF. The first case of COVID-19 was seen in our country on March 11, 2020 and nationwide school closure and lockdown were implemented. School closure and home confinement might have adverse effects on children's physical and mental health. In this study, we aimed to compare the effect of COVID-19 pandemic on psychological reactions of CF patients and healthy controls.

METHODS: This is a controlled cross-sectional study including 7-18 year-old children with CF. The survey included questions regarding family environment and peer relations, self care and psychological reactions to COVID-19 pandemic. The questionnaire was applied to children via telephone call under parental supervision.

RESULTS: We evaluated 132 CF patients and 135 their healthy peers. Mean age was 11.5±2.9 years in CF group and 11.8±3.2 years in control group (p=0.98). There were 55 girls (41.7%) in CF group and 81 girls (60%) in control group (p=0.027). The socioeconomic status of families was similar. CF patients were found to be less anxious for family members having the risk of COVID-19, less upset for school closure, less anxious about the COVID-19 pandemic (p<0.001, 0.02, 0.01 respectively).

CONCLUSION: CF patients seem to show more resilience in coping with the pandemic. Appropriate psychological support should be provided to them and resilience strategies in coping with the pandemic should be nurtured.

PMID:34597455 | DOI:10.1111/ped.15009

Am J Respir Cell Mol Biol. 2021 Oct 1. doi: 10.1165/rcmb.2020-0410OC. Online ahead of print.

ABSTRACT

Neutrophil extracellular traps increase cystic fibrosis (CF) airway inflammation. We hypothesized that macrophage exposure to neutrophil elastase (NE) would trigger the release of macrophage extracellular traps (METs), a novel mechanism to augment NE-induced airway inflammation in CF. To test whether human blood monocyte derived macrophages (hBMDM) from CF and non-CF subjects take up proteolytically active NE resulting in clipping of chromatin binding proteins and the release of METs. Human BMDM from CF and non-CF subjects were treated with FITC-NE to determine NE localization. Intracellular NE activity was determined by DQ-elastin assay. MET DNA release was detected by Pico-green for hBMDM, and visualized by confocal microscopy for hBMDM, and for alveolar macrophages harvested from intratracheal NE-exposed Cftr-null and wild-type littermate mice. Immunofluorescence assays for histone citrullination and western analyses for histone clipping were performed. FITC-NE was localized to cytoplasmic and nuclear domains, and NE retained proteolytic activity in hBMDM. NE (100 to 500 nM) significantly increased extracellular DNA release from hBMDM. NE activated MET release by confocal microscopy in hBMDM, and in alveolar macrophages from Cftr-null and Cftr wild-type mice. NE-triggered MET release was associated with H3 citrullination and partial cleavage of Histone H3 but not H4. Exposure to NE caused release of METs from both CF and non-CF hBMDM in vitro and murine alveolar macrophages in vivo. MET release was associated with NE-activated H3 clipping, a mechanism associated with chromatin decondensation, a prerequisite for METs.

PMID:34597246 | DOI:10.1165/rcmb.2020-0410OC

Radiographics. 2021 Oct;41(6):1766-1784. doi: 10.1148/rg.2021210008.

ABSTRACT

Masses and masslike lesions of the pancreas are uncommon in the pediatric population. However, owing to overlapping clinical and imaging features, it can be challenging to differentiate the various causes of pediatric pancreatic masses at initial patient presentation. Clinical data such as patient age, signs and symptoms at presentation, laboratory test results, and potential underlying cancer predisposition syndrome can be helpful when formulating a differential diagnosis. US may be the first imaging study to depict a pancreatic mass in a child, as this examination is frequently performed in children with nonspecific abdominal signs and symptoms because of its wide availability and relatively low cost and the lack of a need for sedation or anesthesia. CT or MRI is typically required for more thorough characterization of the mass and surgical planning. Complete characterization of pancreatic masses includes assessment of vascular involvement, local invasion, and extrapancreatic spread of tumor. The authors provide an up-to-date comprehensive review of the clinical manifestations, histopathologic features, and imaging findings of primary and secondary tumors of the pancreas in children and young adults. Advances in imaging, current prognostic information, and treatment paradigms also are highlighted. Finally, nontumorous masslike lesions of the pediatric pancreas, including vascular malformations, cystic disorders (eg, von Hippel-Lindau syndrome, cystic fibrosis), intrapancreatic accessory spleen, and autoimmune pancreatitis, are discussed. Online supplemental material is available for this article. ©RSNA, 2021.

PMID:34597223 | DOI:10.1148/rg.2021210008

Pediatr Pulmonol. 2021 Oct 1. doi: 10.1002/ppul.25712. Online ahead of print.

ABSTRACT

BACKGROUND: The marked heterogeneity in CF disease complicates selection of those most likely to benefit from existing or emergent treatments.

OBJECTIVE: We aimed to predict progression of bronchiectasis in preschool children with CF.

METHODS: Using data collected up to three years of age, in the Australian Respiratory Early Surveillance Team for CF (AREST CF) cohort study, clinical information, chest computed tomography (CT) scores and biomarkers from bronchoalveolar lavage were assessed in a multivariable linear regression model as predictors for CT bronchiectasis at age 5-6.

RESULTS: Follow-up at 5-6 years was available in 171 children. Bronchiectasis prevalence at 5-6 was 134/171 (78%) and median bronchiectasis score 3 (range 0-12). The internally validated multivariate model retained eight independent predictors accounting for 37% (Adjusted R2 ) of the variance in bronchiectasis score. The strongest predictors of future bronchiectasis were: pancreatic insufficiency, repeated intravenous treatment courses, recurrent lower respiratory infections in the first 3 years of life and lower airway inflammation. Dichotomizing the resulting prediction score at a bronchiectasis score of above the median resulted in a diagnostic odds ratio of 13 (95% CI 6.3-27) with positive and negative predictive values of 80% (95%CI 72%-86%) and 77% (95% CI 69%-83%) respectively.

CONCLUSION: Early assessment of bronchiectasis risk in children with CF is feasible with reasonable precision at a group level, which can assist in high-risk patient selection for interventional trials. The unexplained variability in disease progression at individual patient level remains high, limiting the use of this model as a clinical prediction tool. This article is protected by copyright. All rights reserved.

PMID:34596357 | DOI:10.1002/ppul.25712

Chirality. 2021 Oct 1. doi: 10.1002/chir.23364. Online ahead of print.

ABSTRACT

Both menthol and its analog WS-12 share the same hydrophobic intra-subunit binding pocket between a voltage-sensor-like domain and a TRP domain in a cold-sensing TRPM8 channel. However, unlike WS-12, menthol upregulates TRPM8 with a low efficacy but a high coefficient of a dose response at membrane hyperpolarization and with ligand stereoselectivity at membrane depolarization. The underlying mechanisms are unknown. Here, this in silico research suggested that the ligand-stereoselective sequential cooperativity between two menthol molecules in the WS-12 pocket is required for allosteric activation of TRPM8. Furthermore, two H-bonded homochiral menthol dimers with both head-to-head and head-to-tail can compete for the WS-12 site via non-covalent interactions. Although both dimers can form an H-bonding network with a voltage sensor S4 to disrupt a S3-S4 salt bridge in the voltage-sensor-like domain to release a "parking brake," only one dimer may drive channel opening by pushing a "gas pedal" in the TRP domain away from the S6 gate against S4. In this way, the efficacy is decreased, but the cooperativity is increased for the menthol effect at membrane hyperpolarization. Therefore, this review may extend a new pathway for ligand-stereoselective allosteric regulation of other voltage- and ligand-gated ion channels by menthol.

PMID:34596287 | DOI:10.1002/chir.23364

J Med Microbiol. 2021 Oct;70(10). doi: 10.1099/jmm.0.001420.

ABSTRACT

Introduction. Pseudomonas aeruginosa produces quorum sensing signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence factor production in the cystic fibrosis (CF) airways.Hypothesis/Gap statement. Culture can lead to condition-dependent artefacts which may limit the potential insights and applications of AQs as minimally-invasive biomarkers of bacterial load.Aim. We aimed to use culture-independent methods to explore the correlations between AQ levels and live P. aeruginosa load in adults with CF.Methodology. Seventy-five sputum samples at clinical stability and 48 paired sputum samples obtained at the beginning and end of IV antibiotics for a pulmonary exacerbation in adults with CF were processed using a viable cell separation technique followed by quantitative P. aeruginosa polymerase chain reaction (qPCR). Live P. aeruginosa qPCR load was compared with the concentrations of three AQs (HHQ, NHQ and HQNO) detected in sputum, plasma and urine.Results. At clinical stability and the beginning of IV antibiotics for pulmonary exacerbation, HHQ, NHQ and HQNO measured in sputum, plasma and urine were consistently positively correlated with live P. aeruginosa qPCR load in sputum, compared to culture. Following systemic antibiotics live P. aeruginosa qPCR load decreased significantly (P<0.001) and was correlated with a reduction in plasma NHQ (plasma: r=0.463, P=0.003).Conclusion. In adults with CF, AQ concentrations correlated more strongly with live P. aeruginosa bacterial load measured by qPCR compared to traditional culture. Prospective studies are required to assess the potential of systemic AQs as biomarkers of P. aeruginosa bacterial burden.

PMID:34596013 | DOI:10.1099/jmm.0.001420

Front Cell Infect Microbiol. 2021 Sep 14;11:698929. doi: 10.3389/fcimb.2021.698929. eCollection 2021.

ABSTRACT

Pseudomonas aeruginosa is a common opportunistic pathogen that causes acute nosocomial necrotizing pneumonia and is the predominant source of chronic lung infections in patients with the genetic disorder cystic fibrosis. Early diagnosis in infected patients and monitoring P. aeruginosa contamination is therefore of great importance in controlling disease spread and development with timely drugs intervention treatment and cut off infection source. Traditional culture-biochemical methods are time consuming and highly dependent on technicians and expensive instruments. To address these challenges, the present study aimed to develop a rapid, sensitive, and specific, on-site detection method for P. aeruginosa based on recombinase polymerase amplification (RPA) combined with lateral flow strip (LFS) technology. The experimental process included screening and modification of primer and probe sets targeting the unique virulence gene elastase B (lasB); specificity detection in 29 strains of P. aeruginosa and 23 closely-related pathogenic bacteria; sensitivity measurements with gradient-diluted P. aeruginosa genomic DNA and probit regression analysis; and clinical application evaluation using 574 patients samples and calculating coincidence rate and kappa index value in comparison with the culture-biochemical method. The P. aeruginosa RPA-LFS assay could complete the amplification process at 37°C constant temperature within 30 min and results could be visualized by the naked eye within 10 min on LFS. The assay displayed high sensitivity with a limit of detection of 3.05 CFU/reaction. It also demonstrated high specificity by showing no cross reaction with other pathogenic bacteria, and rapidness by being completed in less than an hour. Furthermore, when used with clinical samples, the assay had a coincidence rate of 98.26% with the culture-biochemical method and a kappa index value of 0.9433. These data indicate that the RPA-LFS assay represents a major improvement for P. aeruginosa detection, especially in resource-limited areas.

PMID:34595129 | PMC:PMC8478171 | DOI:10.3389/fcimb.2021.698929

Sci Rep. 2021 Sep 30;11(1):19438. doi: 10.1038/s41598-021-98912-x.

ABSTRACT

RNA sequencing enables high-content/high-complexity measurements in small molecule screens. Whereas the costs of DNA sequencing and RNA-seq library preparation have decreased consistently, RNA extraction remains a significant bottleneck to scalability. We evaluate the performance of a bulk RNA-seq library prep protocol optimized for analysis of many samples of adherent cultured cells in parallel. We combined a low-cost direct lysis buffer compatible with cDNA synthesis (in-lysate cDNA synthesis) with Smart-3SEQ and examine the effects of calmidazolium and fludrocortisone-induced perturbation of primary human dermal fibroblasts. We compared this method to normalized purified RNA inputs from matching samples followed by Smart-3SEQ or Illumina TruSeq library prep. Our results show the minimal effect of RNA loading normalization on data quality, measurement of gene expression patterns, and generation of differentially expressed gene lists. We found that in-lysate cDNA synthesis combined with Smart-3SEQ RNA-seq library prep generated high-quality data with similar ranked DEG lists when compared to library prep with extracted RNA or with Illumina TruSeq. Our data show that small molecule screens or experiments based on many perturbations quantified with RNA-seq are feasible at low reagent and time costs.

PMID:34593905 | DOI:10.1038/s41598-021-98912-x

Clin Exp Optom. 2021 Sep 30:1-11. doi: 10.1080/08164622.2021.1974282. Online ahead of print.

ABSTRACT

The tear film is a thin, moist layer covering the ocular surface and is laden with proteins, peptides, lipids, mucins, electrolytes and cellular debris which function to maintain the healthy status of the ocular surface. In many cases of ocular or systemic disease, the integrity of this layer is changed and/or the balance of its constituents is disturbed. Since tears are easy and quick to collect and can be stored for long periods, they have the potential to be a valuable source of information relevant to many disease states. The purpose of this review is to collate information on the known biomarkers of systemic disease that have been identified in tears. The range of conditions covered includes diabetes mellitus, diabetic retinopathy, diabetic peripheral neuropathy, multiple sclerosis, Parkinson's disease, Alzheimer's disease, migraine, systemic sclerosis, cystic fibrosis, thyroid disorders and cancer.

PMID:34592130 | DOI:10.1080/08164622.2021.1974282

Arch Endocrinol Metab. 2021 Sep 29:2359-3997000000404. doi: 10.20945/2359-3997000000404. Online ahead of print.

ABSTRACT

OBJECTIVE: Patients with cystic fibrosis (CF) have a high incidence of pubertal and growth delay. In girls with CF, pubertal delay has an important psychological impact. Still, only a few studies have explored the occurrence of pubertal delay in girls with CF. The aims of this study were to compare the pubertal development of girls with CF compared with healthy controls regarding Tanner staging and pelvic ultrasound and, in girls with CF, correlate the findings with those of spirometry, body mass index, Shwachman-Kulczycki score (SKS), and genotyping.

METHODS: This was a cross-sectional, case-control study including 35 girls with CF aged 6-17 years and following up at the Pediatric Pulmonology Outpatient Clinic of a tertiary hospital. These patients were compared with 59 healthy controls who had undergone pelvic ultrasound as part of another study conducted by the same group. Girls with CF were consecutively enrolled in the study during their annual routine check-up visit. Data collected in the CF group included spirometry and anthropometric results, SKS values, bone age, occurrence of current cystic fibrosis-related diabetes (CFRD) and Pseudomonas aeruginosa colonization, history of meconium ileus, genotype, ultrasound parameters, and Tanner stage.

RESULTS: Pelvic ultrasound findings and Tanner stage reflected less pubertal development in girls with CF compared with healthy controls. Pubertal stage in patients with CF who presented CFRD (3.17 ± 1.16), had chronic colonization by Pseudomonas aeruginosa (3.10 ± 1.10), or were homozygous for the F508del mutation (1.91 ± 1.30) was more delayed than in controls (3.41 ± 1.41). Tanner stage correlated with age at menarche, bone age, and anthropometric and ultrasound data.

CONCLUSION: Girls with CF presented a delay in pubertal development evaluated by Tanner stage and ultrasound parameters, which was more evident in the presence of comorbidities.

PMID:34591408 | DOI:10.20945/2359-3997000000404

Mycopathologia. 2021 Sep 29. doi: 10.1007/s11046-021-00579-5. Online ahead of print.

ABSTRACT

There has been a growing appreciation of the importance of respiratory fungal diseases in recent years, with better understanding of their prevalence as well as their global distribution. In step with the greater awareness of these complex infections, we are currently poised to make major advances in the characterization and treatment of these fungal diseases, which in itself is largely a consequence of post-genomic technologies which have enabled rational drug development and a path towards personalized medicines. These advances are set against a backdrop of globalization and anthropogenic change, which have impacted the world-wide distribution of fungi and antifungal resistance, as well as our built environment. The current revolution in immunomodulatory therapies has led to a rapidly evolving population at-risk for respiratory fungal disease. Whilst challenges are considerable, perhaps the tools we now have to manage these infections are up to this challenge. There has been a welcome acceleration of the antifungal pipeline in recent years, with a number of new drug classes in clinical or pre-clinical development, as well as new focus on inhaled antifungal drug delivery. The "post-genomic" revolution has opened up metagenomic diagnostic approaches spanning host immunogenetics to the fungal mycobiome that have allowed better characterization of respiratory fungal disease endotypes. When these advances are considered together the key challenge is clear: to develop a personalized medicine framework to enable a rational therapeutic approach.

PMID:34590208 | DOI:10.1007/s11046-021-00579-5

Bioeng Transl Med. 2021 Apr 3;6(3):e10222. doi: 10.1002/btm2.10222. eCollection 2021 Sep.

ABSTRACT

The sweat test is the gold standard for the diagnosis of cystic fibrosis (CF). The test utilizes iontophoresis to administer pilocarpine to the skin to induce sweating for measurement of chloride concentration in sweat. However, the sweat test procedure needs to be conducted in an accredited lab with dedicated instrumentation, and it can lead to inadequate sweat samples being collected in newborn babies and young children due to variable sweat production with pilocarpine iontophoresis. We tested the feasibility of using microneedle (MN) patches as an alternative to iontophoresis to administer pilocarpine to induce sweating. Pilocarpine-loaded MN patches were developed. Both MN patches and iontophoresis were applied on horses to induce sweating. The sweat was collected to compare the sweat volume and chloride concentration. The patches contained an array of 100 MNs measuring 600 μm long that were made of water-soluble materials encapsulating pilocarpine nitrate. When manually pressed to the skin, the MN patches delivered >0.5 mg/cm2 pilocarpine, which was double that administered by iontophoresis. When administered to horses, MN patches generated the same volume of sweat when normalized to drug dose and more sweat when normalized to skin area compared to iontophoresis using a commercial device. Moreover, both MN patches and iontophoresis generated sweat with comparable chloride concentration. These results suggest that administration of pilocarpine by MN patches may provide a simpler and more-accessible alternative to iontophoresis for performing a sweat test for the diagnosis of CF.

PMID:34589599 | PMC:PMC8459588 | DOI:10.1002/btm2.10222