Highly Efficient Gene Editing of Cystic Fibrosis Patient-Derived Airway Basal Cells Results in Functional CFTR Correction.

Mol Ther. 2020 Apr 29;:

Authors: Suzuki S, Crane AM, Anirudhan V, Barillà C, Matthias N, Randell SH, Rab A, Sorscher EJ, Kerschner JL, Yin S, Harris A, Mendel M, Kim K, Zhang L, Conway A, Davis BR

Abstract
There is a strong rationale to consider future cell therapeutic approaches for cystic fibrosis (CF) in which autologous proximal airway basal stem cells, corrected for CFTR mutations, are transplanted into the patient's lungs. We assessed the possibility of editing the CFTR locus in these cells using zinc-finger nucleases and have pursued two approaches. The first, mutation-specific correction, is a footprint-free method replacing the CFTR mutation with corrected sequences. We have applied this approach for correction of ΔF508, demonstrating restoration of mature CFTR protein and function in air-liquid interface cultures established from bulk edited basal cells. The second is targeting integration of a partial CFTR cDNA within an intron of the endogenous CFTR gene, providing correction for all CFTR mutations downstream of the integration and exploiting the native CFTR promoter and chromatin architecture for physiologically relevant expression. Without selection, we observed highly efficient, site-specific targeted integration in basal cells carrying various CFTR mutations and demonstrated restored CFTR function at therapeutically relevant levels. Significantly, Omni-ATAC-seq analysis revealed minimal impact on the positions of open chromatin within the native CFTR locus. These results demonstrate efficient functional correction of CFTR and provide a platform for further ex vivo and in vivo editing.

PMID: 32402246 [PubMed - as supplied by publisher]

APPEAL-1: A multiple country European survey assessing the psychosocial impact of peanut allergy.

Allergy. 2020 May 13;:

Authors: DunnGalvin A, Blumchen K, Timmermans F, Regent L, Schnadt S, Podestà M, Sánchez Á, Couratier P, Feeney M, Hjorth B, Patel R, Lush T, Ryan R, Vereda A, Fernández-Rivas M, Fisher HR

Abstract
BACKGROUND: Peanut allergy (PA) is a common, potentially life-threatening, and typically lifelong condition with a significant burden of illness. However, information is lacking on how persons with PA (PwPA) and their caregivers perceive the psychosocial impact of living with PA. The Allergy to Peanuts imPacting Emotions And Life study 1 (APPEAL-1) survey, conducted across Europe, investigated the experience and impact of living with PA. Here, we report data evaluating the psychosocial impact of PA on PwPA and their caregivers.
METHODS: APPEAL-1 was an online survey conducted in 8 European countries. Representatives of 8 patient advocacy groups and 5 healthcare-research specialists developed the survey. Eligible respondent groups included: adults diagnosed with PA (self-report); parent/nonparent caregivers (proxy-report for a child with PA); and parent/nonparent caregivers (self-report of PA impact on themselves).
RESULTS: Of 1846 total study respondents, 419 were adults with PA (self-report); 546 were parents/ caregivers (proxy-report) ; 881 were parents/caregivers (self-report). Most respondents reported lifestyle restrictions regarding food (84-93%) and additional domains including parties and socializing, holiday activities and destinations, and taking public transport (53-89%). Approximately 40% rated themselves as "very" frustrated and "very" stressed. Two-thirds (65%) felt socially isolated; 43% were bullied. Less than half felt confident in knowing when to use an adrenaline autoinjector. Several intercountry differences were observed such as high levels of uncertainty and stress in respondents from Ireland, highest rates of anxiety in respondents from Germany, and social exclusion and isolation most common in respondents from France.
CONCLUSIONS: PA imposes an adverse psychosocial impact on patients and caregivers, leading to frustration, stress, and isolation. Attention to the impact of PA is needed in research and clinical practice to improve PA healthcare and public education programs.

PMID: 32400915 [PubMed - as supplied by publisher]

Improved Fmoc-solid-phase peptide synthesis of an extracellular loop of CFTR for antibody selection by the phage display technology.

J Pept Sci. 2020 May 12;:e3253

Authors: Ferreira VFC, Correia JDG, Farinha CM, Mendes F

Abstract
Cystic fibrosis (CF), a life-shortening genetic disease, is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that codes for the CFTR protein, the major chloride channel expressed at the apical membrane of epithelial cells. The development of an imaging probe capable of non-invasively detect CFTR at the cell surface could be of great advantage for the management of CF. With that purpose, we synthesized the first extracellular loop of CFTR protein (ECL1) through fluorenylmethyloxycarbonyl (Fmoc)-based microwave-assisted solid-phase peptide synthesis (SPPS), according to a reported methodology. However, aspartimide formation, a well-characterized side reaction in Fmoc-SPPS, prompted us to adopt a different side-chain protection strategy for aspartic acid residues present in ECL1 sequence. The peptide was subsequently modified via PEGylation and biotinylation, and cyclized through disulfide bridge formation, mimicking the native loop conformation in CFTR protein. Herein, we report improvements in the synthesis of the first extracellular loop of CFTR, including peptide modifications that can be used to improve antigen presentation in phage display for selection of novel antibodies against plasma membrane CFTR.

PMID: 32400108 [PubMed - as supplied by publisher]

Development of bacterial resistance during treatment with topical gentamicin for chronic rhinosinusitis in patients with cystic fibrosis and primary ciliary dyskinesis. Retrospective case series.

Otolaryngol Pol. 2020 Jan 28;74(3):33-40

Authors: Kisiel M, Sjölander I, Klar A, Asplund Stenkvist M, Laurell G

Abstract
BACKGROUND: The management of chronic rhinosinusitis (CRS) in patients with cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) is still a challenge. At our institution we have used gentamycin nasal spray, extemporaneously produced, for prophylactic treatment of moderate-to-severe CRS. The aim of this study was to investigate the gentamycin susceptibility of bacteria in sputum samples in CF and PCD patients treated for CRS.
METHODOLOGY: Patients with CF and PCD who were prescribed gentamycin nasal spray for CRS and had sputum bacterial cultures taken pre-treatment and followed-up at least once after ≥6 months were retrospectively included. Microbiological data were descriptively analysed in terms of bacterial species and resistance to gentamycin.
RESULTS: A case series of 17 CF and 12 PCD patients passed the inclusion criteria. Of those cases, three (18%) CF patients and one (8%) PCD patient developed resistance to gentamycin during treatment with gentamycin nasal spray. In all four cases, the resistant bacterial isolates were <i>P. aeruginosa</i>. Additionally, two CF patients already had <i>P. aeruginosa </i> isolates resistant to gentamycin in the pre-treatment culture. In further two CF patients, the multi-resistant <i>Burgdorferi cepacia </i>complex, including gentamycin resistance, was identified. <i>P. aeruginosa </i> and <i>S. aureus </i> in CF and <i>P. aeruginosa</i> and <i>H. influenza </i> in PCD were the predominant bacterial species.
CONCLUSIONS: The study showed that there was moderate incidence of gentamycin resistance in CF and PCD patients at our institution. However, further prospective studies are needed to confirm the outcomes.

PMID: 32398382 [PubMed - in process]

Morbidity and mortality in carriers of the cystic fibrosis mutation CFTR Phe508del in the general population.

Eur Respir J. 2020 May 12;:

Authors: Çolak Y, Nordestgaard BG, Afzal S

Abstract
Cystic fibrosis is caused by autosomal-recessive inheritance of a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR), up to 90% due to Phe508del mutation in the CFTR gene. We tested the hypothesis that CFTR Phe508del carriers versus non-carriers in the general population have increased morbidity and mortality.We genotyped 108 035 randomly selected white Danish individuals aged 20-100 from the Copenhagen General Population Study for CFTR Phe508del (rs113993960). We assessed risk of chronic bronchitis and airflow limitation cross-sectionally, and overall survival and risk of bronchiectasis, lung cancer, pneumonia, chronic rhinosinusitis, airway bleeding, spontaneous pneumothorax, respiratory failure, acute and chronic pancreatitis, liver cirrhosis, ileus, gastric and colorectal cancer, and male infertility prospectively during up to 15 years follow-up (median:9 years). A single individual was excluded due to homozygosity for CFTR Phe508del and known cystic fibrosis. No other individuals had diagnosed cystic fibrosis at baseline examination or during follow-up.Among 108 034 individuals, 105 176(97%) were non-carriers and 2858(3%) were carriers, i.e. heterozygous for CFTR Phe508del. Overall survival was similar between carriers and non-carriers. Compared to non-carriers and multivariable adjusted, carriers had odds ratio of 1.31(95% confidence interval:1.16-1.48) for chronic bronchitis, hazard ratio of 1.88(1.03-3.45) for bronchiectasis, and hazard ratio of 1.52(1.12-2.08) for lung cancer. Carriers did not differ from non-carriers concerning lung function or any other morbidity outcomes as mentioned above.In the general population, carriers of CFTR Phe508del have a normal lifespan but an increased risk of chronic bronchitis by 1.3-fold, bronchiectasis by 1.9-fold, and lung cancer by 1.5-fold.

PMID: 32398304 [PubMed - as supplied by publisher]

Blood eosinophils predict inhaled fluticasone response in bronchiectasis.

Eur Respir J. 2020 May 12;:

Authors: Aliberti S, Sotgiu G, Blasi F, Saderi L, Posadas T, Martinez Garcia MA

PMID: 32398295 [PubMed - as supplied by publisher]

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics.

Respir Res. 2020 May 12;21(1):111

Authors: Brown R, Nath S, Lora A, Samaha G, Elgamal Z, Kaiser R, Taggart C, Weldon S, Geraghty P

Abstract
Dysregulated expression and activity of cathepsin S (CTSS), a lysosomal protease and a member of the cysteine cathepsin protease family, is linked to the pathogenesis of multiple diseases, including a number of conditions affecting the lungs. Extracellular CTSS has potent elastase activity and by processing cytokines and host defense proteins, it also plays a role in the regulation of inflammation. CTSS has also been linked to G-coupled protein receptor activation and possesses an important intracellular role in major histocompatibility complex class II antigen presentation. Modulated CTSS activity is also associated with pulmonary disease comorbidities, such as cancer, cardiovascular disease, and diabetes. CTSS is expressed in a wide variety of immune cells and is biologically active at neutral pH. Herein, we review the significance of CTSS signaling in pulmonary diseases and associated comorbidities. We also discuss CTSS as a plausible therapeutic target and describe recent and current clinical trials examining CTSS inhibition as a means for treatment.

PMID: 32398133 [PubMed - in process]

Exposure of Mycobacterium abscessus to Environmental Stress and Clinically Used Antibiotics Reveals Common Proteome Response among Pathogenic Mycobacteria.

Microorganisms. 2020 May 09;8(5):

Authors: Rojony R, Danelishvili L, Campeau A, Wozniak JM, Gonzalez DJ, Bermudez LE

Abstract
Mycobacterium abscessus subsp. abscessus (MAB) is a clinically important nontuberculous mycobacterium (NTM) causing pulmonary infection in patients such as cystic fibrosis and bronchiectasis. MAB is naturally resistant to the majority of available antibiotics. In attempts to identify the fundamental response of MAB to aerobic, anaerobic, and biofilm conditions (as it is encountered in patients) and during exposure to antibiotics, we studied bacterial proteome using tandem mass tag mass spectrometry sequencing. Numerous de novo synthesized proteins belonging to diverse metabolic pathways were found in anaerobic and biofilm conditions, including glycolysis/gluconeogenesis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation, nitrogen metabolism, and glyoxylate and dicarboxylate metabolism. Upon exposure to amikacin and linezolid under stress environments, MAB displayed metabolic enrichment for glycerophospholipid metabolism and oxidative phosphorylation. By comparing proteomes of two significant NTMs, MAB and M. avium subsp. hominissuis, we found highly synthesized shared enzymes of oxidative phosphorylation, TCA cycle, glycolysis/gluconeogenesis, glyoxylate/dicarboxylate, nitrogen metabolism, peptidoglycan biosynthesis, and glycerophospholipid/glycerolipid metabolism. The activation of peptidoglycan and fatty acid biosynthesis pathways indicates the attempt of bacteria to modify the cell wall, influencing the susceptibility to antibiotics. This study establishes global changes in the synthesis of enzymes promoting the metabolic shift and enhancing the pathogen resistance to antibiotics within different environments.

PMID: 32397563 [PubMed]

Synthesis and Therapeutic Applications of Iminosugars in Cystic Fibrosis.

Int J Mol Sci. 2020 May 09;21(9):

Authors: Esposito A, D'Alonzo D, Fenza M, Gregorio E, Tamanini A, Lippi G, Dechecchi MC, Guaragna A

Abstract
Iminosugars are sugar analogues endowed with a high pharmacological potential. The wide range of biological activities exhibited by these glycomimetics associated with their excellent drug profile make them attractive therapeutic candidates for several medical interventions. The ability of iminosugars to act as inhibitors or enhancers of carbohydrate-processing enzymes suggests their potential use as therapeutics for the treatment of cystic fibrosis (CF). Herein we review the most relevant advances in the field, paying attention to both the chemical synthesis of the iminosugars and their biological evaluations, resulting from in vitro and in vivo assays. Starting from the example of the marketed drug NBDNJ (N-butyl deoxynojirimycin), a variety of iminosugars have exhibited the capacity to rescue the trafficking of F508del-CFTR (deletion of F508 residue in the CF transmembrane conductance regulator), either alone or in combination with other correctors. Interesting results have also been obtained when iminosugars were considered as anti-inflammatory agents in CF lung disease. The data herein reported demonstrate that iminosugars hold considerable potential to be applied for both therapeutic purposes.

PMID: 32397443 [PubMed - in process]

Immunomodulation in Cystic Fibrosis: Why and How?

Int J Mol Sci. 2020 May 08;21(9):

Authors: Giacalone VD, Dobosh BS, Gaggar A, Tirouvanziam R, Margaroli C

Abstract
Cystic fibrosis (CF) lung disease is characterized by unconventional mechanisms of inflammation, implicating a chronic immune response dominated by innate immune cells. Historically, therapeutic development has focused on the mutated cystic fibrosis transmembrane conductance regulator (CFTR), leading to the discovery of small molecules aiming at modulating and potentiating the presence and activity of CFTR at the plasma membrane. However, treatment burden sustained by CF patients, side effects of current medications, and recent advances in other therapeutic areas have highlighted the need to develop novel disease targeting of the inflammatory component driving CF lung damage. Furthermore, current issues with standard treatment emphasize the need for directed lung therapies that could minimize systemic side effects. Here, we summarize current treatment used to target immune cells in the lungs, and highlight potential benefits and caveats of novel therapeutic strategies.

PMID: 32397175 [PubMed - in process]

Mycobacterium abscessus and Antibiotic Resistance: Same As It Ever Was.

Clin Infect Dis. 2019 10 30;69(10):1687-1689

Authors: Griffith DE

PMID: 30689764 [PubMed - indexed for MEDLINE]

Factors associated with severe lung disease in an adult population with cystic fibrosis: a single center experience.

Turk J Med Sci. 2020 May 12;:

Authors: Er B, Çelebioğlu E, Yalçin E, Doğru D, Erden Aki Ö, Uzun Ö, Akova M, Özçelik U, Kiper N, Emri S

Abstract
BACKGROUND/AIM: The patients with cystic fibrosis (CF) are living longer, but respiratory failure is still the most common cause of mortality. The aim of this study is to investigate factors associated with severe lung disease in a cohort of adult patients with CF.
MATERIALS AND METHODS: Demographic data, clinical and laboratory findings of the patients aged 18 years and more were collected and the patients were grouped according to forced expiratory volume in 1 second (FEV1) as severe group: < 40% and non-severe ? 40%. Associations were investigated between groups and clinical outcomes.
RESULTS: A total of 76 patients were enrolled in the study. The mean age was 24.5±5.25 years and 36 (47.4%) patients were female. In the severe group; the mean age was higher (27.1±6.0 vs 23.6±4.7, p=0.013), the median Chrispin-Norman score of severe lung disease group was higher (14 (6-22) vs 5.5 (0-20), p< 0.001), hospitalization at least once in a year for intravenous antibiotic was more common (12/18 (66%) vs 19/58 (32%), p=0.014). There was a positive correlation between body mass index (BMI) and lung function, indicating that lower nutritional status was related to lower FEV1, r2=0.21, p<0.001. The median FEV1% was lower in patients with CF-related diabetes (38 (14-95) vs 66 (13-121), p=0.042). Dornase alpha use and physiotherapy rate were higher in severe lung disease group (p=0.008 and p< 0.001, respectively).
CONCLUSION: Lower BMI, older age, presence of CF-related diabetes, higher radiologic scores, use of dornase alpha and physiotherapy and higher hospitalization rate for intravenous antibiotic therapy are significantly associated with severe lung disease.

PMID: 32394679 [PubMed - as supplied by publisher]

The role of essential fatty acids in cystic fibrosis and normalizing effect of fenretinide.

Cell Mol Life Sci. 2020 May 11;:

Authors: Garić D, Dumut DC, Shah J, De Sanctis JB, Radzioch D

Abstract
Cystic fibrosis (CF) is the most common autosomal-recessive disease in Caucasians caused by mutations in the CF transmembrane regulator (CFTR) gene. Patients are usually diagnosed in infancy and are burdened with extensive medical treatments throughout their lives. One of the first documented biochemical defects in CF, which predates the cloning of CFTR gene for almost three decades, is an imbalance in the levels of polyunsaturated fatty acids (PUFAs). The principal hallmarks of this imbalance are increased levels of arachidonic acid and decreased levels of docosahexaenoic acids (DHA) in CF. This pro-inflammatory profile of PUFAs is an important component of sterile inflammation in CF, which is known to be detrimental, rather than protective for the patients. Despite decades of intensive research, the mechanistic basis of this phenomenon remains unclear. In this review we summarized the current knowledge on the biochemistry of PUFAs, with a focus on the metabolism of AA and DHA in CF. Finally, a synthetic retinoid called fenretinide (N-(4-hydroxy-phenyl) retinamide) was shown to be able to correct the pro-inflammatory imbalance of PUFAs in CF. Therefore, its pharmacological actions and clinical potential are briefly discussed as well.

PMID: 32394023 [PubMed - as supplied by publisher]

COVID-19: A message of hope from a young girl with severe cystic fibrosis.

Pediatr Pulmonol. 2020 May 11;:

Authors: Blanchon S, Fernandez C, Guerin S, Crisinel PA, Rochat I

PMID: 32392382 [PubMed - as supplied by publisher]

Functional genomics analysis of human colon organoids identifies key transcription factors.

Physiol Genomics. 2020 May 11;:

Authors: Yin S, Ray G, Kerschner JL, Hao S, Perez A, Drumm M, Browne J, Leir SH, Longworth M, Harris A

Abstract
Organoids are a valuable 3D model to study the differentiated functions of the human intestinal epithelium. They are a particularly powerful tool to measure epithelial transport processes in health and disease. Though biological assays such as organoid swelling and intraluminal pH measurements are well established, their underlying functional genomics are not well characterized. Here we combine genome-wide analysis of open chromatin by ATAC-seq with transcriptome mapping by RNA-seq to define the genomic signature of human intestinal organoids (HIOs). These data provide an important tool for investigating key physiological and biochemical processes in the intestinal epithelium. We next compared the transcriptome and open chromatin profiles of HIOs with equivalent datasets from the Caco2 colorectal carcinoma line, which is an important 2D model of the intestinal epithelium. Our results define common features of the intestinal epithelium in HIO and Caco2 and further illustrate the cancer-associated program of the cell line. Generation of Caco2 cysts enabled interrogation of the molecular divergence of the 2D and 3D cultures. Over-represented motif analysis of open chromatin peaks identified Caudal Type Homeobox 2 (CDX2) as a key activating transcription factor in HIO, but not in monolayer cultures of Caco2. However, the CDX2 motif becomes overrepresented in open chromatin from Caco2 cysts, reinforcing the importance of this factor in intestinal epithelial differentiation and function. Intersection of the HIO and Caco2 transcriptomes further showed functional overlap in pathways of ion transport and tight junction integrity, among others. These data contribute to understanding human intestinal organoid biology.

PMID: 32390556 [PubMed - as supplied by publisher]

Genetic Variation Near chrXq22-q23 Is Linked to Emotional Functioning in Cystic Fibrosis.

Biol Res Nurs. 2020 May 11;:1099800420924125

Authors: Barbato E, Daly B, Douglas S, Kerr M, Litman P, Darrah R

Abstract
INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive disease that affects many organ systems, most notably the pulmonary and gastrointestinal systems. Through genome-wide association studies, multiple genetic regions modifying CF-related pulmonary and gastrointestinal symptoms have been identified, but translation of these findings to clinical benefit remains elusive. Symptom variation in CF patients has been associated with changes in health-related quality of life (HRQOL), but the relationship between CF symptom-modifying genetic loci and HRQOL has not been explored. The purpose of this study was to determine whether two previously identified genetic modifiers of CF-related pathology also modify the subscales of HRQOL.
METHODS: HRQOL and genotype data were obtained and analyzed. Linear regressions were used to examine the amount of variance in HRQOL subscales that could be explained by genotype for each modifier locus.
RESULTS: A significant regression equation was found between genotype for rs5952223, a variant near chrXq22-q23, and emotional functioning in a sample of 129 CF patients.
DISCUSSION: These data suggest that genotype for this single-nucleotide polymorphism is associated with emotional functioning in CF patients and highlight this genetic region as a potential therapeutic target, irrespective of CF transmembrane conductance regulator genotype.

PMID: 32390518 [PubMed - as supplied by publisher]

Prevalence of constipation in cystic fibrosis patients: a systematic review of observational studies.

J Pediatr (Rio J). 2020 May 07;:

Authors: Stefano MA, Poderoso RE, Mainz JG, Ribeiro JD, Ribeiro AF, Lomazi EA

Abstract
OBJECTIVE: To systematically revise the literature in search of data about the prevalence of constipation in patients with cystic fibrosis (CF) according to the publications in this field, which partly refer to guidelines defined in 2010 by The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).
SOURCES: Systematic review selecting articles based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), including CF patients of all ages. Sources of information were selected to identify the articles without period limitation for the searching: CADTH - Canadian Agency for Drugs and Technologies in Health, CINAHL Complete, Clinical Trials US NIH, Cochrane Library, Embase, MEDLINE via Ovid, Scopus, Web Of Science, PubMed, SciELO, MEDLINE and LILACS through the Biblioteca Virtual em Saúde (BVS), Health Systems Evidence, PDQ Evidence, CRD Canadian Agency for Drugs and Technologies in Health, INAHTA - International Network of Agencies for Health Technology Assessment, and PEDro.
FINDINGS: The prevalence of constipation in CF patients was reported in eight observational studies. Only two studies assessed the frequency of constipation as a primary objective; in the others, constipation was quoted along with the prevalence of the spectrum of gastrointestinal manifestations. Altogether, the publications included 2018 patients, and the reported prevalence varied widely from 10% to 57%. Only two of the six articles published after 2010 followed the definition recommended by the ESPGHAN.
CONCLUSIONS: Constipation is a frequent but still insufficiently assessed complaint of CF patients. The use of diverse diagnostic criteria restricts comparison and epidemiological conclusions, thus future studies should compulsorily apply the ESPGHAN definition.

PMID: 32389617 [PubMed - as supplied by publisher]

Combined Lung-Liver and Delayed Kidney Transplantation for Cystic Fibrosis Clinical Approach and Outcome: A Case Report.

Transplant Proc. 2020 May 07;:

Authors: Zhang T, Price MB, Bravo N, Villarreal JA, Kueht ML, Vierling JM, Cotton R, Galvan T, O'Mahony CA, Goss JA, Rana A

Abstract
Reports on the long-term outcomes and immunosuppressive regimens of multiorgan transplant patients are limited. Here, we describe a patient with cystic fibrosis complicated by multiorgan failure who was successfully treated with combined liver lung transplant and delayed kidney transplant, resulting in excellent outcomes. Delayed kidney transplant was done to reduce the operative stress of a single procedure, giving time for adequate resuscitation and weaning from vasopressors. Our patient's postoperative course was complicated by post-transplant lymphoproliferative disease, which was successfully treated with rituximab and reduced dosages of immunosuppression.

PMID: 32389488 [PubMed - as supplied by publisher]

Phenotypes of Chronic Rhinosinusitis.

J Allergy Clin Immunol Pract. 2020 May;8(5):1505-1511

Authors: Cho SH, Hamilos DL, Han DH, Laidlaw TM

Abstract
Chronic rhinosinusitis (CRS) is a complex heterogeneous disease with different phenotypes and endotypes. Recent advances in our understanding of the pathogenetic mechanisms of CRS endotypes have led to the introduction of effective biologic agents for CRS management. Traditionally, CRS phenotypes have been divided into with or without nasal polyps depending on the presence of polyps. Although this classification does not reflect the various endotypes that are recently emerging, it is simple and easily recognized by clinicians. Other phenotypes of CRS are fungal rhinosinusitis (including invasive and noninvasive subtypes), infectious rhinosinusitis, aspirin-exacerbated respiratory disease, cystic fibrosis, pediatric CRS, and CRS associated with systemic diseases. This article reviews the diagnostic approaches and up-to-date treatment strategies for each CRS phenotype with the hope that a better understanding of endotypes will result in a more scientific understanding of phenotypes and precise, personalized treatments.

PMID: 32389275 [PubMed - in process]

Location, location, location: lessons from airway epithelial anion channels.

J Physiol. 2019 12;597(24):5739-5740

Authors: Delpiano L, Gray MA

PMID: 31654403 [PubMed - indexed for MEDLINE]