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"Cystic Fibrosis"

These pubmed results were generated on 2020/06/23

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Parotitis due to Burkholderia cepacia Infection after Autologous Hematopoietic Stem Cell Transplantation.

Transpl Infect Dis. 2020 Jun 21;:e13374

Authors: Xu H, Yang Y, Yan J, Huang D, Liu X

Abstract
Burkholderia cepacia predominantly causes opportunistic infections in hospitalized and immunocompromised patients such as patients with cystic fibrosis, cancer, or human immunodeficiency virus (HIV). Nonetheless, Burkholderia cepacia is infrequently reported to cause infection in hematopoietic stem cell transplantation (HSCT) recipients. Herein, we report a rare case of suppurative parotitis in a 31-year-old patient with T-cell lymphoblastic lymphoma (T-LBL) who underwent auto-HSCT. The secretion from the Stensen duct was collected, and Burkholderia cepacia was detected using the VITEK-2 identification system. Additionally, sensitive antibiotic therapy against this bacterium was also effective. This is the first case of parotitis triggered by Burkholderia cepacia after auto-HSCT, and it is also the first reported domestic case. This case emphasizes the importance of considering bacterial infections in general and Burkholderia cepacia specifically in HSCT patients with post-transplant parotitis.

PMID: 32564412 [PubMed - as supplied by publisher]

Haplotype analysis of the CFTR gene on normal and mutant CFTR genes.

Mutat Res. 2020 May 23;821:111708

Authors: Karimi N, Bidemeshki Pour A, Alibakhshi R, Almasi S

Abstract
BACKGROUND: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are responsible for Cystic Fibrosis (CF) disease. Since the distribution of polymorphisms varies among populations, a comparison between the frequency of CFTR polymorphisms in patients and healthy population may further identify their role in CF disease. The results obtained from this research may facilitate the prediction of disease phenotype in prenatal diagnosis or newborn screening program as well as determine the possible associations between haplotypes and specific mutations.
METHODS: Blood samples collected from 27 unrelated West Iranian families contain at least one CF patient and 55 control families with no history of CF. Samples were analyzed for c.1210-12 T [5-9], c.1242-35-1242-12GT [8-10], c.744-33GATT [6-8] and c.869 + 11C > T polymorphisms by automated direct DNA sequencing following DNA extraction.
RESULTS: Our results showed that the T7 allele is the most common allele in normal and non-ΔF508 CF chromosomes with the frequencies of 93.6% and 100%, respectively. Conversely, T9 was the only allele detected in ΔF508 chromosomes. Moreover, the c.1242-35-1242-12GT analysis showed that (TG)11 repeat was the most common dinucleotide repeat in both, non-ΔF508 and normal chromosomes with the frequencies of 91% and 71%, respectively. The c.744-33GATT and c.869 + 11C > T polymorphism analyses indicated that (GATT)6 and T allele are only found in ΔF508 CF chromosomes. Besides, the [T7-TG11-GATT7-C] haplotype was the most common haplotype in both, normal and non-ΔF508 CF subjects while the [T9-TG10- GATT6-T] haplotype was only detected in CF patients carrying ΔF508 mutation.
CONCLUSIONS: Our findings identified an informative haplotype that could be used in genetic counseling, prenatal diagnosis and future screening of CF in Iran.

PMID: 32563932 [PubMed - as supplied by publisher]

Antimicrobial resistance: Concerns of healthcare providers and people with CF.

J Cyst Fibros. 2020 Jun 17;:

Authors: Bullington W, Hempstead S, Smyth AR, Drevinek P, Saiman L, Waters VJ, Bell SC, VanDevanter DR, Flume PA, Elborn S, Muhlebach MS, Antimicrobial Resistance International Working Group in Cystic Fibrosis

Abstract
BACKGROUND: Chronic lung infections and their treatment pose risks for the development of antimicrobial resistance (AMR) in people with cystic fibrosis (PWCF). In this study, we evaluated the attitudes of healthcare providers' (HCP) and PWCF or their parents' toward AMR within the international CF community.
METHODS: HCP and PWCF identified through listservs and CF-related organizations were asked to complete an AMR centered survey, with additional questions on antimicrobial stewardship (AMS) for HCP. Descriptive analyses are reported.
RESULTS: The responding 443 HCP and 464 PWCF/Parents were from 30 and 25 countries, respectively. Sixty-two percent of HCP and 56% of PWCF stated they were "very concerned" about AMR, with Pseudomonas spp. and Burkholderia spp. considered the most concerning organisms for both HCP and PWCF/Parents. Non-tuberculous mycobacteria were of greater concern to HCP compared to PWCF/Parents. There was a discrepancy regarding AMR education to PWCF, with 80% of HCP stating having discussed this with PWCF/Parents, but only 50% of PWCF recalling such discussions.
CONCLUSION: These results highlight that AMR is relevant to CF HCP and PWCF internationally, indicating that educational tools and research are warranted.

PMID: 32563724 [PubMed - as supplied by publisher]

Enigmatic variations: the many facets of CFTR function in the heart.

Acta Physiol (Oxf). 2020 Jun 20;:e13525

Authors: James AF

Abstract
It has long been known that cardiac myocytes release ATP, and that the release of ATP is increased in response to hypoxia and ischaemia. The mechanisms underlying that release and its regulation, however, remain unclear. In this issue of Acta Physiologica, Wang and colleagues from the Ballard lab present intriguing new evidence of a role for the cystic fibrosis transmembrane conductance regulator (CFTR) in the release of ATP from cardiac myocytes in response to simulated ischaemia.

PMID: 32562586 [PubMed - as supplied by publisher]

Acrodermatitis Enteropathica as a Presentation of Cystic Fibrosis in an Infant.

Indian Pediatr. 2020 Jun 15;57(6):573

Authors: Madhusudan M, Raman R, Sathyasekaran M

PMID: 32562404 [PubMed - as supplied by publisher]

Chronic Granulomatous Disease with the McLeod Phenotype: a French National Retrospective Case Series.

J Clin Immunol. 2020 Jun 19;:

Authors: Lhomme F, Peyrard T, Babinet J, Abou-Chahla W, Durieu I, Moshous D, Neven B, Rohrlich PS, Albinni S, Amiranoff D, Dumont MD, Lortholary O, Héritier S, Marguet C, Suarez F, Fischer A, Blanche S, Hermine O, Mahlaoui N

Abstract
BACKGROUND: X-linked chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the CYBB gene (located on Xp21.1). Patients with large deletions on chromosome Xp21.1 can present with the McLeod phenotype and also Duchenne muscular dystrophy or retinitis pigmentosa. The objective of the present study was to describe a series of French patients with CGD and the McLeod phenotype.
METHODS: We retrospectively collected data from the medical records of 8 patients with CGD and the McLeod phenotype registered at the French National Reference Center for blood types.
RESULTS: The median age at diagnosis of CGD was 1.2 years, the median age at diagnosis of the McLeod phenotype was 4.5 years, and the median length of follow-up was 15.2 years. Four patients displayed allo-immunization, with anti-KEL20 and anti-XK1 (formerly known as anti-KL) antibodies. Five of the 6 patients with available blood smears had acanthocytosis. Neuropsychiatric, muscle-related, and ocular manifestations were present in 4, 2, and 1 of the patients, respectively. Three of the 4 patients having undergone allogeneic hematopoietic stem cell transplantation (HSCT) are alive. Overall, 5 patients are alive, and 3 are alive and well.
CONCLUSION: This is the largest yet descriptive study of a series of patients with X-linked CGD and the McLeod phenotype. Although this disease combination is rare, the timely, accurate diagnosis of the McLeod phenotype is critical because of the serious post-transfusion complications. However, HSCT can be considered in these patients.

PMID: 32562208 [PubMed - as supplied by publisher]

"Management of Community-Acquired Pneumonia in Immunocompromised Adults: A Consensus Statement Regarding Initial Strategies".

Chest. 2020 Jun 16;:

Authors: Ramirez JA, Musher DM, Evans SE, Dela Cruz C, Crothers KA, Hage CA, Aliberti S, Anzueto A, Arancibia F, Arnold F, Azoulay E, Blasi F, Bordon J, Burdette S, Cao B, Cavallazzi R, Chalmers J, Charles P, Chastre J, Claessens YE, Dean N, Duval X, Fartoukh M, Feldman C, File T, Froes F, Furmanek S, Gnoni M, Lopardo G, Luna C, Maruyama T, Menendez R, Metersky M, Mildvan D, Mortensen E, Niederman MS, Pletz M, Rello J, Restrepo MI, Shindo Y, Torres A, Waterer G, Webb B, Welte T, Witzenrath M, Wunderink R

Abstract
BACKGROUND: Community-acquired pneumonia (CAP) guidelines have improved the management and outcomes of patients with CAP, primarily by standardization of initial empiric therapy. But current society-published guidelines exclude immunocompromised patients.
RESEARCH QUESTION: There is no concensus regarding the initial management of immunocompromised patients with suspected CAP.
STUDY DESIGN AND METHODS: This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the management of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus.
RESULTS: The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiological work-up, general principles of empiric therapy, and empiric therapy for specific pathogens.
INTERPRETATION: This document offer general suggestions for the initial management of the immunocompromised patient who arrives at the hospital with pneumonia.

PMID: 32561442 [PubMed - as supplied by publisher]

Postprandial changes in gastrointestinal function and transit in cystic fibrosis assessed by Magnetic Resonance Imaging.

J Cyst Fibros. 2020 Jun 16;:

Authors: Ng C, Dellschaft NS, Hoad CL, Marciani L, Ban L, Prayle AP, Barr HL, Jaudszus A, Mainz JG, Spiller RC, Gowland P, Major G, Smyth AR

Abstract
BACKGROUND: Cystic fibrosis (CF) is a multi-system genetic disorder affecting >72,000 people worldwide. Most CF patients experience gastrointestinal symptoms and can develop complications. However, the mechanisms of CF gut disease are not well understood. We evaluated gut function and transit in CF using magnetic resonance imaging (MRI). We hypothesised oro-caecal transit time (OCTT) is longer in CF; with lower small bowel water content (SBWC).
METHODS: Twelve CF patients aged 12-40 years and 12 age and sex-matched controls underwent serial MRIs over 1 day with standardised meals. The primary endpoint was OCTT, assessed by the appearance of a food bolus in the caecum. Other measures included corrected SBWC and corrected colonic volume (both area under the curve, AUC), gastric half-emptying time and gastrointestinal symptoms.
RESULTS: OCTT was longer in CF (CF 330 mins [270, >360] vs. controls 210 mins [173, 315], p = 0.04), with no difference in gastric half-emptying times. Corrected SBWC was higher in CF (CF 62 L.min/m2 [36, 80] vs. controls 34 L.min/m2 [28, 41], p = 0.021); minimal postprandial decrease between T240 and T300 (CF 13 mL/m2 [-13, 57] vs. controls 102 mL/m2 [67, 108], p = 0.002) suggests impaired ileal emptying. Corrected colonic volumes were higher in CF (CF 186 L.min/m2 [167, 206] vs. controls 123 L.min/m2 [89, 146], p = 0.012). There were no differences in gastrointestinal symptoms.
CONCLUSIONS: MRI provides novel insights into CF pathophysiology. Sub-clinical ileal obstruction may be more prevalent than previously thought. Gastrointestinal MRI shows promise as an investigational tool in CF.

PMID: 32561324 [PubMed - as supplied by publisher]

In silico integrative analysis predicts relevant properties of exotoxin-derived peptides for the design of vaccines against Pseudomonas aeruginosa.

Infect Genet Evol. 2020 Jun 16;:104424

Authors: Terra ACG, Salvador EA

Abstract
Pseudomonas aeruginosa (PA) is an opportunistic human pathogen responsible for causing serious infections in patients with cystic fibrosis. Infections caused by PA are difficult to treat and eradicate due to intrinsic and added resistance to antibiotic therapy. Therefore, it is necessary to establish effective prevention strategies against this infectious agent. In this study, a combination of immunoinformatic tools was applied to predict immunogenic and immunodominant regions in the structure of exotoxins commonly secreted as virulence factors in PA infection (ExoA, ExoS, ExoT, ExoU and ExoY). The peptides derived from exotoxins were evaluated for the potential affinity for human leukocyte antigen (HLA) I and HLA-II molecules, antigenicity score and toxicity profile. From an initial screening of 941 peptides, 13 (1.38%) were successful in all analyzes. The peptides with relevant immunogenic properties were mainly those derived from Exo A (10 / 76.9%). All peptides selected in the last analysis present a high population coverage rate based on the interaction of HLA alleles (95.36 ± 7.83%). Therefore, the peptides characterized in this study are recommended for in vitro and in vivo studies and can provide the basis for the rational design of a vaccine against PA.

PMID: 32561294 [PubMed - as supplied by publisher]

Efficacy and safety of aerosolized intra-tracheal dornase alfa administration in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS): a structured summary of a study protocol for a randomised controlled trial.

Trials. 2020 Jun 19;21(1):548

Authors: Desilles JP, Gregoire C, Le Cossec C, Lambert J, Mophawe O, Losser MR, Lambiotte F, Le Tacon S, Cantier M, Engrand N, Trouiller P, Pottecher J

Abstract
OBJECTIVES: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may trigger severe pneumonia in coronavirus disease of 2019 (COVID-19) patients through release of damage-associated molecular patterns (DAMPs) and recruitment of neutrophils in the lungs. Activated neutrophils induce inflammation and severe alveolar injury by releasing neutrophil extracellular traps (NETs). The backbones of many DAMPs and NETs are made of extracellular, cell-free DNA decorated with highly toxic compounds such as elastase, myeloperoxidase and citrullinated histones. Dornase alfa is a FDA-approved recombinant human DNAse 1 for the treatment of cystic fibrosis, which cleaves extracellular DNA and may break up cell-free DNA, loosening sticky mucus in the distal airways and reducing NETs-induced toxicity on alveolar pneumocytes. The COVIDornase trial intends to define the impact of aerosolized intra-tracheal dornase alfa administration on the severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19 patients. This drug might make lung mucus thinner and looser, promoting improved clearance of secretions and reduce extracellular double-stranded DNA-induced hyperinflammation in alveoli, preventing further damage to the lungs.
TRIAL DESIGN: COVIDornase is a prospective, randomized, controlled, 2-arm (1:1 ratio), multicentric, open-label clinical trial.
PARTICIPANTS: The study will recruit mechanically ventilated patients hospitalized in the intensive care unit (ICU) in the recruiting centres (at the time of writing: The Rothschild foundation hospital in Paris, the Strasbourg university hospitals, and Metz-Thionville hospital) who have been diagnosed with COVID-19 and meet ARDS criteria.
INCLUSION CRITERIA: - Adult patient (age ≥ 18 years old); - Hospitalized in ICU; - With severe COVID-19 pneumonia and ARDS according to Berlin criteria (PaO2/FiO2 < 300 and PEEP > 5 cmH2O); - Intubated for less than 8 days; - With an anticipated duration of mechanical ventilation > 48 hours; - Carrier of an arterial catheter; - For whom 4 PaO2/FiO2 values over the preceding 24 hours are available; NON-INCLUSION CRITERIA: - Known hypersensitivity to dornase alfa or any of its excipients; - Pregnant or breastfeeding status; - Patient under legal protection.
INTERVENTION AND COMPARATOR: Intervention 1, Study group Dornase alfa (Pulmozyme®, Roche, Switzerland) will be administered by aerosol, at a dose of 2500 IU twice daily, 12 hours apart, for 7 consecutive days, using a vibrating mesh nebulizer (Aerogen Solo®, Aerogen, Ireland). The remainder of the management will be performed in accordance with good clinical practice, including mechanical ventilation (protective ventilation, PEEP > 5 cmH2O, tracheal balloon pressure check every 4 hours or automatic device, 30° head of the bed elevation, tidal volume 6-8mL/kg, plateau pressure < 30 cmH2O), neuromuscular blockers if necessary, prone position if PaO2/FiO2 < 150, early enteral nutrition, glycemic control and a sedation protocol based on the RASS score. Intervention 2, Comparator Patients will receive usual care in accordance with good practice (as detailed above), without aerosols.
MAIN OUTCOMES: The primary outcome is the occurrence of at least one grade improvement between D0 (inclusion) and D7 in the ARDS scale severity (Berlin criteria). For instance from "severe" to "moderate" or from "moderate" to "mild".
RANDOMISATION: All consecutive patients meeting the inclusion criteria will be randomised 1:1 using an eCRF-based, computer-generated randomisation table, either to the dornase alfa arm or to the control arm. An interim analysis will be performed after inclusion of 20 patients. Inclusions may be stopped at the interim analysis per data safety and monitoring board (DSMB) advice, if statistical analyses conclude on the futility or efficacy of the intervention or by other DSMB decision.
BLINDING (MASKING): The participants and caregivers will not be blinded to study group assignment. Those assessing the outcomes will be blinded to study group assignment.
NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Fifty patients will be randomized to each group, 100 patients in total.
TRIAL STATUS: Protocol version number 2, April 29th, 2020. Recruitment is ongoing. The trial started recruitment on the 21st April 2020. We estimate recruitment will finish August 21st 2020.
TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov on 21 April 2020, updated on 8 May 2020. Trial registration number is NCT04355364.
FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated. This Letter serves as a summary of the key elements of the full protocol.

PMID: 32560746 [PubMed - as supplied by publisher]

MiRNA Expression Profile in the Airways is Altered during Pulmonary Exacerbation in Children with Cystic Fibrosis-A Preliminary Report.

J Clin Med. 2020 Jun 16;9(6):

Authors: Stachowiak Z, Wojsyk-Banaszak I, Jończyk-Potoczna K, Narożna B, Langwiński W, Kycler Z, Sobkowiak P, Bręborowicz A, Szczepankiewicz A

Abstract
MicroRNAs are small non-coding RNAs that regulate immune response and inflammation. We assumed that miRNAs may be involved in the immune response during cystic fibrosis pulmonary exacerbations (CFPE) and that altered expression profile in the airways and blood may underlie clinical outcomes in CF pediatric patients.
METHODS: We included 30 pediatric patients diagnosed with cystic fibrosis. The biologic material (blood, sputum, exhaled breath condensate) was collected during pulmonary exacerbation and in stable condition. The miRNA expression profile from blood and sputum (n = 6) was done using the next-generation sequencing. For validation, selected four miRNAs were analyzed by qPCR in exosomes from sputum supernatant and exhaled breath condensate (n = 24). NGS analysis was done in Base Space, correlations of gene expression with clinical data were done in Statistica.
RESULTS: The miRNA profiling showed that four miRNAs (miR-223, miR-451a, miR-27b-3p, miR-486-5p) were significantly altered during pulmonary exacerbation in CF patients in sputum but did not differ significantly in blood. MiRNA differently expressed in exhaled breath condensate (EBC) and sputum showed correlation with clinical parameters in CFPE.
CONCLUSION: MiRNA expression profile changes in the airways during pulmonary exacerbation in CF pediatric patients. We suggest that miRNA alterations during CFPE are restricted to the airways and strongly correlate with clinical outcome.

PMID: 32560275 [PubMed - as supplied by publisher]

Unusual presentation of CF in an infant.

Respir Med Case Rep. 2020;30:101110

Authors: Portillo Miño JD, Cerón Muñoz EE

Abstract
This case report attempts an approach to the clinical findings of hepatobiliary manifestations in Cystic Fibrosis. Infant less than 1-month-old with an insidious clinical picture that debut with hepatobiliary manifestations and jaundice, upper respiratory infection and gastrointestinal sepsis non-specific. Cystic Fibrosis is the most frequent autosomal recessive clinical condition in Caucasians. It is associated with liver involvement around 30%. In children, hepatobiliary symptoms occur at puberty when damage to the liver system is in advanced stages. The atypical presentation of Cystic Fibrosis with liver involvement is very rare and lethal. Understanding the different form of Cystic Fibrosis, it is essential for early diagnosis and to achieve integral management.

PMID: 32551223 [PubMed]

EAACI Guideline on the effective transition of adolescents and young adults with allergy and asthma.

Allergy. 2020 Jun 19;:

Authors: Roberts G, Vazquez-Ortiz M, Knibb R, Khaleva E, Alviani C, Angier E, Blumchen K, Comberiati P, Duca B, DunnGalvin A, Garriga-Baraut T, Gore C, Gowland MH, Hox V, Jensen B, Mortz CG, Pfaar O, Pite H, Santos AF, Sanchez-Garcia S, Timmermans F

Abstract
Adolescent and young adult (AYA) patients need additional support while they experience the challenges associated with their age. They need specific training to learn the knowledge and skills required to confidently self-manage their allergies and/or asthma. Transitional care is a complex process which should address the psychological, medical, educational and vocational needs of AYA in the developmentally appropriate way. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline to provide evidence-based recommendations for healthcare professionals to support the transitional care of AYA with allergy and/or asthma. This guideline was developed by a multi-disciplinary working panel of experts and patient representatives based on two recent systematic reviews. It sets out a series of general recommendations on operating a clinical service for AYA, which include: (i) starting transition early (11-13 years), (ii) using a structured, multidisciplinary approach, (iii) ensuring AYA fully understand their condition and have resources they can access, (iv) active monitoring of adherence and (v) discussing any implications for further education and work. Specific allergy and asthma transition recommendations include (i) simplifying medication regimes and using reminders; (ii) focusing on areas where AYA are not confident and involving peers in training AYA patients; (iii) identifying and managing psychological and socioeconomic issues impacting disease control and quality of life; (iv) enrolling the family in assisting AYA to undertake self-management and (v) encouraging AYA to let their friends know about their allergies and asthma. These recommendations may need to be adapted to fit into national healthcare systems.

PMID: 32558994 [PubMed - as supplied by publisher]

Adherence and barriers to general and respiratory exercises in Cystic Fibrosis.

Pediatr Pulmonol. 2020 Jun 19;:

Authors: Santuzzi CH, Liberato FMG, Morau SAC, de Oliveira NFF, Nascimento LR

Abstract
OBJECTIVES: To investigate the adherence and the self-reported barriers to general and respiratory exercises reported by individuals with Cystic Fibrosis.
STUDY DESIGN: An exploratory, experimental study.
METHODS: Community-dwelling individuals aged 16 years and over, diagnosed with Cystic Fibrosis, who were accompanied in referral centres were included. Information regarding adherence to exercises was obtained by a questionnaire, and reported as a ratio between prescribed exercises and self-reported adherence. Weekly frequency was used to verify adherence to exercise initiation, and the amount of session duration concluded was used to verify adherence to exercise duration. Values above 0.70 were considered as high adherence. Eight demographic and clinical factors were examined to explore their relationships with adherence, and the barriers to exercises were also collected by questionnaire.
RESULTS: Thirty-four participants met the inclusion criteria. Overall, adherence to exercise initiation was 0.40 (SD 0.3) for general exercises, and 0.63 (SD 0.4) for respiratory exercises. Adherence to exercise duration was 0.76 (SD 0.4) for general exercises, and 0.73 (SD 0.4) for respiratory exercises. Forced vital capacity (r=0.39; p=0.02) was associated with adherence to the duration of general exercises, and body mass index (r=-0.33; p=0.05) was associated with adherence to the duration of respiratory exercises. The main reported barriers were lack of interest, motivation and time, tiredness, non-commitment and do not recognizing benefits of exercises.
CONCLUSIONS: Individuals with Cystic Fibrosis minded completing the sessions of prescribed exercises once they have initiated it, but most of the days they did not practice general or respiratory exercises. This article is protected by copyright. All rights reserved.

PMID: 32558990 [PubMed - as supplied by publisher]

[Allergic bronchopulmonary aspergillosis].

Rev Med Suisse. 2020 Jun 17;16(698):1250-1255

Authors: Reinhard-Groebli F, Fellrath JM

Abstract
Allergic bronchopulmonary aspergillosis (ABPA) is a specific complex immunological response to the spores of Aspergillus fumigatus (Af) colonizing the bronchi of asthmatic or cystic fibrosis patients. Recurrent episodes of bronchial obstruction and inflammation, as well as mucoid impaction cause bronchiectasis, pulmonary infiltrates and fibrotic alterations of the lung parenchyma, resulting in significant morbidity and mortality. The pathogenesis of ABPA remains incompletely understood, so it is not clear why certain colonized subjects develop hypersensitivity to Af, and why some sensitized patients develop ABPA and others do not. There is no simple and specific test for diagnosing ABPA. The diagnosis is based on the combination of clinical, radiological and immunological criteria. Systemic steroids are the cornerstone of treatment.

PMID: 32558454 [PubMed - in process]

[Revolution in the treatment of cystic fibrosis].

Rev Med Suisse. 2020 Jun 17;16(698):1229-1235

Authors: Sauty A, Plojoux J, Mornand A, Blanchon S, Koutsokera A

Abstract
Cystic Fibrosis is a genetic disorder resulting in the absence or dysfunction of the CFTR protein, a chloride channel present on the surface of epithelia, particularly respiratory. Until recently, treatments only concerned the consequences of the disease. But a new type of molecules called « modulators », is already available to some patients and targets the origin of the disease. « Modulators » are divided into « potentiators », which improve the transport of chloride by the CFTR protein, and « correctors », increasing the amount of CFTR proteins. An oral triple therapy combining a potentiator and two correctors has just been approved in the USA and will treat 85 % of patients. The clinical benefit of « modulators » is remarkable, and these drugs are revolutionizing the treatment of Cystic Fibrosis.

PMID: 32558451 [PubMed - in process]

Surgical outcomes in aspirin-exacerbated respiratory disease without aspirin desensitization.

Int Forum Allergy Rhinol. 2020 Jun 18;:

Authors: Grose E, Lee DJ, Yip J, Cottrell J, Sykes J, Lee JK, Lee JM

Abstract
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) represents a severe endotype of chronic rhinosinusitis with nasal polyposis. Although aspirin desensitization (AD) has emerged as an effective therapeutic option, the natural history of AERD without AD remains unclear.
METHODS: A retrospective review was conducted of AERD patients who underwent endoscopic sinus surgery (ESS) without AD between 2010 and 2019. The primary outcomes were revision surgery rate and time to revision surgery. Secondary outcomes included changes in 22-item Sino-Nasal Outcome Test (SNOT-22) scores and Lund-Kennedy endoscopy scores (LKES). A subgroup analysis was performed for patients on monoclonal antibody therapy (MAT).
RESULTS: Of 141 patients, 37 (26.2%) underwent revision ESS with a median time to revision of 3.3 (interquartile range [IQR], 2.2-4.9) years. The probability of remaining free of revision surgery at 1, 3, and 5 years was: 98.2% (95% confidence interval [CI], 95.7-100.0%), 78.8% (95% CI, 70.2-88.4%), and 44.8% (95% CI, 32.4-62.1%), respectively. SNOT-22 scores decreased by 34 (IQR, 18-52) points at 6 months and 27 (IQR, 20-46) points at 1 year postoperatively. In the revision cohort, the decrease in SNOT-22 score was not sustained at 1 year postoperatively. No difference was found in time to revision compared with those without MAT (p = 0.23).
CONCLUSION: A significant proportion of AERD patients benefit from ESS and medical therapy alone without AD. This study presents preliminary results on the impact of MAT on surgical outcomes as it is limited by the small sample size. Further research on the use of MAT in AERD is needed.

PMID: 32558318 [PubMed - as supplied by publisher]

Similarities and differences for membranotropic action of three unnatural antimicrobial peptides.

J Pept Sci. 2020 Jun 18;:e3270

Authors: Oliva R, Chino M, Lombardi A, Nastri F, Notomista E, Petraccone L, Del Vecchio P

Abstract
Previously, we described the design and synthesis of three nine-residue AMPs, P9Nal(SS), P9Trp(SS), and P9Nal(SR), showing high stability in serum and broad spectrum antimicrobial activity. The peptides P9Trp(SS) and P9Nal(SR) differ from P9Nal(SS) for the replacement of the two 2Nal residues with Trp residues and for the replacement of the two Cys (StBu) with Cys (tBu) residues, respectively. These changes led to peptides with a lower hydrophobicity respect to the P9Nal(SS). Interestingly, the three peptides have very similar activity against Gram-negative bacteria. Instead, they exhibit a significant difference towards Gram-positive bacteria, being P9Nal(SS) the most active. In order to evaluate the impact of amino acids substitution on membranotropic activity and rationalize the observed effects in vivo, here, we report the detailed biophysical characterization of the interaction between P9Nal(SR) and P9Trp(SS) and liposomes by combining differential scanning calorimetry, circular dichroism, and fluorescence spectroscopy. The comparison with the results for the previously characterized P9Nal(SS) peptide reveals similarities and differences on the interaction process and perturbation activities. It was found that the three peptides can penetrate at different extent inside the bilayer upon changing their conformation and inducing lipid domains formation, revealing that the formation of lipid domains is fundamental for the activity against Gram-negative bacteria. On the contrary, the dissimilar activity against Gram-positive bacteria well correlate with the different affinity of peptides for the lipoteichoic acid, a component selectively present in the cell wall of Gram-positive bacteria.

PMID: 32558092 [PubMed - as supplied by publisher]

CFTR targeted therapies: recent advances in cystic fibrosis and possibilities in other diseases of the airways.

Eur Respir Rev. 2020 Jun 30;29(156):

Authors: Patel SD, Bono TR, Rowe SM, Solomon GM

Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion transporter that regulates mucus hydration, viscosity and acidity of the airway epithelial surface. Genetic defects in CFTR impair regulation of mucus homeostasis, causing severe defects of mucociliary clearance as seen in cystic fibrosis. Recent work has established that CFTR dysfunction can be acquired in chronic obstructive pulmonary disease (COPD) and may also contribute to other diseases that share clinical features of cystic fibrosis, such as asthma, allergic bronchopulmonary aspergillosis and bronchiectasis. Protean causes of CFTR dysfunction have been identified including cigarette smoke exposure, toxic metals and downstream effects of neutrophil activation pathways. Recently, CFTR modulators, small molecule agents that potentiate CFTR or restore diminished protein levels at the cell surface, have been successfully developed for various CFTR gene defects, prompting interest in their use to treat diseases of acquired dysfunction. The spectrum of CFTR dysfunction, strategies for CFTR modulation, and candidate diseases for CFTR modulation beyond cystic fibrosis will be reviewed in this manuscript.

PMID: 32554756 [PubMed - in process]