Protease-activated receptor 2 activates airway apical membrane chloride permeability and increases ciliary beating.

FASEB J. 2017 Sep 05;:

Authors: McMahon DB, Workman AD, Kohanski MA, Carey RM, Freund JR, Hariri BM, Chen B, Doghramji LJ, Adappa ND, Palmer JN, Kennedy DW, Lee RJ

Abstract
Mucociliary clearance, driven by the engine of ciliary beating, is the primary physical airway defense against inhaled pathogens and irritants. A better understanding of the regulation of ciliary beating and mucociliary transport is necessary for identifying new receptor targets to stimulate improved clearance in airway diseases, such as cystic fibrosis and chronic rhinosinusitis. In this study, we examined the protease-activated receptor (PAR)-2, a GPCR previously shown to regulate airway cell cytokine and mucus secretion, and transepithelial Cl(-) current. PAR-2 is activated by proteases secreted by airway neutrophils and pathogens. We cultured various airway cell lines, primary human and mouse sinonasal cells, and human bronchial cells at air-liquid interface and examined them using molecular biology, biochemistry, and live-cell imaging. We found that PAR-2 is expressed basolaterally, where it stimulates both intracellular Ca(2+) release and Ca(2+) influx, which activates low-level nitric oxide production, increases apical membrane Cl(-) permeability ∼3-5-fold, and increases ciliary beating ∼20-50%. No molecular or functional evidence of PAR-4 was observed. These data suggest a novel and previously overlooked role of PAR-2 in airway physiology, adding to our understanding of the role of this receptor in airway Ca(2+) signaling and innate immunity.-McMahon, D. B., Workman, A. D., Kohanski, M. A., Carey, R. M., Freund, J. R., Hariri, B. M., Chen, B., Doghramji, L. J., Adappa, N. D., Palmer, J. N., Kennedy, D. W., Lee, R. J. Protease-activated receptor 2 activates airway apical membrane chloride permeability and increases ciliary beating.

PMID: 28874459 [PubMed - as supplied by publisher]

Antagonism between front line antibiotics clarithromycin and amikacin used for the treatment of Mycobacterium abscessus infections is mediated by the whiB7 gene.

Antimicrob Agents Chemother. 2017 Sep 05;:

Authors: Pryjma M, Burian J, Kuchinski K, Thompson CJ

Abstract
Combinations of antibiotics, each individually effective against Mycobacterium abscessus, are routinely co-administered based on the concept that this minimizes the spread of antibiotic resistance. However, our in vitro data contradicts this assumption and instead documents antagonistic interactions between two antibiotics (clarithromycin and amikacin) used to treat M. abscessus infections. Clinically relevant concentrations of clarithromycin induced increased resistance to both amikacin and itself. Induction of resistance was dependent on whiB7, a transcriptional activator of intrinsic antibiotic resistance that is induced by exposure to many different antibiotics. In M. abscessus, deletion of whiB7 (MAB_3508c) resulted in increased sensitivity to a broad range of antibiotics. WhiB7 was required for transcriptional activation of genes that confer resistance to three commonly used anti-M. abscessus drugs: clarithromycin, amikacin, and tigecycline. The whiB7-dependent gene that conferred macrolide resistance was identified as erm(41) (MAB_2297), a ribosomal methyltransferase. The whiB7-dependent gene contributing to amikacin resistance was eis2 (MAB_4532c), a GNAT acetyl transferase. Transcription of whiB7 and resistance genes in its regulon was inducible by subinhibitory concentrations of clarithromycin but not by amikacin. Thus, exposure to clarithromycin, or likely any whiB7-inducing antibiotic, may antagonize the activity of amikacin and other drugs. This has important implications for management of M. abscessus infections, both in cystic fibrosis (CF) and non-CF patients.

PMID: 28874379 [PubMed - as supplied by publisher]

Mycobacterium abscessus WhiB7 regulates a species -specific repertoire of genes to confer extreme antibiotic resistance.

Antimicrob Agents Chemother. 2017 Sep 05;:

Authors: Hurst-Hess K, Rudra P, Ghosh P

Abstract
Mycobacterium abscessus causes acute and chronic broncho-pulmonary infection in patients with chronic lung damage, of which cystic fibrosis (CF) patients are particularly vulnerable. The major threat posed by this organism is its high intrinsic antibiotic resistance. A typical treatment regimen involves a 6-12 month long combination therapy of clarithromycin and amikacin, with cure rates below 50% and multiple side effects, especially due to amikacin. In the present work we show that M. abscessuswhiB7, a homologue of M. tuberculosis and M. smegmatis whiB7 with previously demonstrated effects on intrinsic antibiotic resistance, is strongly induced when exposed to clinically relevant antibiotics that target the ribosome - erythromycin, clarithromycin, amikacin, tetracycline and spectinomycin. Deletion of M. abscessuswhiB7 results in sensitivity to all of the above antibiotics. Further, we have defined and compared the whiB7 regulon of M. abscessus with the closely related (non-tuberculous mycobacterium) NTM, M. smegmatis to demonstrate the induction of species-specific repertoire of genes. Further we show that one such gene, eis2, is specifically induced in M. abscessus by whiB7, and contributes to its higher levels of intrinsic amikacin resistance. This species-specific pattern of gene induction could account for the differences in drug susceptibilities to other antibiotics and between different mycobacterial species.

PMID: 28874378 [PubMed - as supplied by publisher]

Hyperbaric oxygen sensitizes anoxic Pseudomonas aeruginosa biofilm to ciprofloxacin.

Antimicrob Agents Chemother. 2017 Sep 05;:

Authors: Kolpen M, Lerche CJ, Kragh KN, Sams T, Koren K, Jensen AS, Line L, Bjarnsholt T, Ciofu O, Moser C, Kühl M, Høiby N, Jensen PØ

Abstract
Chronic Pseudomonas aeruginosa lung infection is characterized by the presence of endobronchial antibiotic-tolerant biofilm subject to strong oxygen (O2) depletion due to the activity of surrounding polymorphonuclear leukocytes. The exact mechanisms affecting the antibiotic susceptibility of biofilms remain unclear, but accumulating evidence suggests that the efficacy of several bactericidal antibiotics is enhanced by stimulation of aerobic respiration of pathogens, while lack of O2 increases their tolerance. In fact, the bactericidal effect of several antibiotics depends on active aerobic metabolism activity and the endogenous formation of reactive O2 radicals (ROS). In this study we aimed to apply hyperbaric oxygen treatment (HBOT) in order to sensitize anoxic P. aeruginosa agarose-biofilms established to mimic situations with intense O2 consumption by the host response in the cystic fibrosis (CF) lung. Application of HBOT resulted in enhanced bactericidal activity of ciprofloxacin at clinically relevant durations and was accompanied by indications of restored aerobic respiration, involvement of endogenous lethal oxidative stress and increased bacterial growth. The findings highlight that oxygenation by HBOT improves the bactericidal activity of ciprofloxacin on P. aeruginosa biofilm and suggest that bacterial biofilms is sensitized to antibiotics by supplying hyperbaric O2.

PMID: 28874373 [PubMed - as supplied by publisher]

Anion-Selective Cholesterol Decorated Macrocyclic Transmembrane Ion Carriers.

J Am Chem Soc. 2017 Sep 05;:

Authors: Behera H, Madhavan N

Abstract
Anion transporters play a vital role in cellular processes and their dysregulation leads to a range of diseases such as cystic fibrosis, Bartter's syndrome and epilepsy. Synthetic chloride transporters are known to induce apoptosis in cancer cell lines. Herein, we report macrocycles that are easily synthesized and externally functionalized by pendant membrane-permeable groups. Among a variety of chains appended onto the macrocycle scaffold, cholesterol is found to be the best with an EC50 value of 0.44 µM. The macrocycle is highly anion-selective and transports ions via an OH¯/X¯ antiport mechanism. The macrocycle is an interesting scaffold for ion-transport as it is able to discriminate between various anions and shows a preference for SCN¯ and Cl¯. Such anion-selective transporters are highly attractive model systems to study ion-transport mechanisms and could potentially be of high therapeutic value.

PMID: 28874045 [PubMed - as supplied by publisher]

Pro-Secretory Activity and Pharmacology in Rabbits of an Aminophenyl-1,3,5-Triazine CFTR Activator for Dry Eye Disorders.

Invest Ophthalmol Vis Sci. 2017 Sep 01;58(11):4506-4513

Authors: Felix CM, Lee S, Levin MH, Verkman AS

Abstract
Purpose: Pharmacological activation of ocular surface cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels is a potential pro-secretory approach to treat dry eye disorders. We previously reported the discovery of aminophenyl-1,3,5-triazines, one of which, N-methyl-N-phenyl-6-(2,2,3,3-tetrafluoropropoxy)-1,3,5-triazine-2,4-diamine (herein called CFTRact-K267), fully activated human wildtype CFTR with EC50 ∼ 30 nM and increased tear volume for 8 hours in mice. Here, functional and pharmacological studies of CFTRact-K267 were done in adult New Zealand white rabbits.
Methods: CFTR chloride conductance was measured in vivo by ocular surface potential differences and in ex vivo conjunctiva by short-circuit current. Tear volume was measured by the Schirmer tear test II and CFTRact-K267 pharmacokinetics and tissue distribution by liquid chromatography/mass spectrometry. Toxicity profile was studied for 28 days with twice-daily topical administration.
Results: Electrophysiological measurements in vivo and in ex vivo conjunctiva demonstrated CFTR activation by CFTRact-K267. A single topical dose of 3 nmol CFTRact-K267 increased tear production by >5 mm for 9 hours by the Schirmer tear test, with predicted therapeutic concentrations maintained in tear fluid. No tachyphylaxis was seen following 28-day twice-daily administration, and changes were not observed in corneal surface integrity or thickness, intraocular pressure, or ocular histology. At day 28, CFTRact-K267 was concentrated in the cornea and conjunctiva and was not detectable in blood or peripheral organs.
Conclusions: These studies support the development of CFTRact-K267 as a pro-secretory therapy for dry eye disorders.

PMID: 28873176 [PubMed - in process]

Physical Activity and Sedentary Time Patterns in Children and Adolescents with Cystic Fibrosis and Age- and Sex-Matched Healthy Controls.

J Phys Act Health. 2017 Sep 05;:1-24

Authors: Mackintosh KA, Ridgers ND, Evans RE, McNarry MA

Abstract
BACKGROUND: Regular physical activity (PA) is increasingly recognised as important in the care of patients with Cystic Fibrosis (CF) but there is a dearth of evidence regarding physical activity levels (PAL) or how these are accrued in those with CF.
METHODS: Physical activity was measured by a hip-worn accelerometer for seven consecutive days by eighteen children (10 boys; 12.4 ± 2.8 years) with mild to moderate CF and eighteen age- and sex-matched controls (10 boys; 12.5 ± 2.7 years).
RESULTS: Both CF and healthy children demonstrated similar PAL and patterns of accumulation across the intensity spectrum, with higher levels of PA during weekdays in both groups. FEV1 was predicted by high-light PA in CF compared to low-light PA in healthy children.
CONCLUSION: These findings highlight weekends and light PA as areas warranting further research for the development of effective intervention strategies to increase PA in the youth CF population.

PMID: 28872398 [PubMed - as supplied by publisher]

Risk and Outcomes of Pulmonary Fungal Infection after Pediatric Lung Transplantation.

Clin Transplant. 2017 Sep 04;:

Authors: Ammerman E, Sweet S, Fenchel M, Storch GA, Conrad C, Hayes D, Faro A, Goldfarb S, Melicoff E, Schecter M, Visner G, Williams N, Danziger-Isakov L

Abstract
BACKGROUND: Prospective studies to determine associated risk factors and related outcomes for pulmonary fungal infection (PFI) after pediatric lung transplant (PLT) are lacking.
METHODS: NIH-sponsored Clinical Trials in Organ Transplantation in Children enrolled PLT candidates, collecting data prospectively for 2 years post-transplant. Demographics, signs/symptoms, radiology, pathology and microbiology were collected. Analyses evaluated for PFI-related risks and outcomes.
RESULTS: In 59 PLT, pre-transplant fungal colonization occurred in 6 donors and 15 recipients. Cystic fibrosis (CF) was associated with pre-transplant colonization (p<0.01). Twenty-five (42%) PLT had 26 post-transplant colonizations (median=67d, range=0-750d) with Candida(13), Aspergillus(4), mold(6) or yeast(3). Post-PLT colonization was not associated with CF, age or pre-PLT colonization. Thirteen PFIs occurred in 10(17%) patients, 3 proven (Candida species) and 10 probable (Candida[3], Aspergillus[3], Penicillium[3], and mold[1]). PFI was preceded by post-PLT colonization with the same organism in 4 of 13 PFI, but post-PLT colonization did not predict subsequent PFI(p=0.87). Older age at transplant was a risk for PFI(p<0.01). No mortality was attributed to PFI. Prophylaxis use was not associated with decreased post-PLT colonization (p=0.60) or PFI (p=0.48).
CONCLUSION: In PLT, PFI and fungal colonization are common but without associated mortality. Post-PLT colonization did not predict PFI. Optimal prevention strategies require additional study. This article is protected by copyright. All rights reserved.

PMID: 28871606 [PubMed - as supplied by publisher]

Inert gas washout: background and application in various lung diseases.

Swiss Med Wkly. 2017 Sep 05;147:w14483

Authors: Usemann J, Yammine S, Singer F, Latzin P

Abstract
Multiple breath inert gas washout (MBW) is a lung function technique to measure ventilation inhomogeneity. The technique was developed more than 60 years ago, but not much used for many decades. Technical improvements, easy protocols and higher sensitivity compared with standard lung function tests in some disease groups have led to a recent renaissance of MBW. The lung clearance index (LCI) is a common measure derived from MBW tests, and offers information on lung pathology complementary to that from conventional lung function tests such as spirometry. The LCI measures the overall degree of pulmonary ventilation inhomogeneity. There are other MBW-derived parameters, which describe more regional airway ventilation and enable specific information on conductive or acinar ventilation inhomogeneity. How this specific ventilation distribution is exactly related to different disease processes has not entirely been examined yet. MBW measurements are performed during tidal breathing, making this technique attractive for children, even young children and infants. These benefits and the additional physiological information on ventilation inhomogeneity early in the course of lung diseases have led to increasing research activities and clinical application of MBW, especially in paediatric lung diseases such as cystic fibrosis (CF). In these patients, LCI detects early airway damage and enables monitoring of disease progression and treatment response. Guidelines for the standardisation of the MBW technique were recently published. These guidelines will, hopefully, increase comparability of LCI data obtained in different centres or intervention trials in children and adults. In this non-systematic review article, we provide an overview of recent developments in MBW, with a special focus on children. We first explain the physiological and technical background to this technique with a short explanation of several methodological aspects that are important for understanding the principle behind the technique and enable high quality measurements. We then provide examples of MBW application in different lung diseases of children and adults, with regards to both clinical application and research activities. Lastly, we report on ongoing clinical trials using MBW as outcome and give an outlook on possible future developments.

PMID: 28871575 [PubMed - in process]

Suppression of chronic inflammation with engineered nanomaterials delivering nuclear factor κB transcription factor decoy oligodeoxynucleotides.

Drug Deliv. 2017 Nov;24(1):1249-1261

Authors: Farahmand L, Darvishi B, Majidzadeh-A K

Abstract
As a prototypical pro-inflammatory transcription factor, constitutive activation of NF-κB signaling pathway has been reported in several chronic inflammatory disorders including inflammatory bowel disease, cystic fibrosis, rheumatoid arthritis and cancer. Application of decoy oligodeoxynucleotides (ODNs) against NF-κB, as an effective molecular therapy approach, has brought about several promising outcomes in treatment of chronic inflammatory disorders. However, systematic administration of these genetic constructs is mostly hampered due to their instability, rapid degradation by nucleases and poor cellular uptake. Both chemical modification and application of delivery systems have shown to effectively overcome some of these limitations. Among different administered delivery systems, nanomaterials have gained much attention for delivering NF-κB decoy ODNs owing to their high loading capacity, targeted delivery and ease of synthesis. In this review, we highlight some of the most recently developed nanomaterial-based delivery systems for overcoming limitations associated with clinical application of these genetic constructs.

PMID: 28870118 [PubMed - in process]

CFTR-NHERF2-LPA₂ Complex in the Airway and Gut Epithelia.

Int J Mol Sci. 2017 Sep 04;18(9):

Authors: Zhang W, Zhang Z, Zhang Y, Naren AP

Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP- and cGMP-regulated chloride (Cl(-)) and bicarbonate (HCO₃(-)) channel localized primarily at the apical plasma membrane of epithelial cells lining the airway, gut and exocrine glands, where it is responsible for transepithelial salt and water transport. Several human diseases are associated with altered CFTR channel function. Cystic fibrosis (CF) is caused by the absence or dysfunction of CFTR channel activity, resulting from mutations in the gene. Secretory diarrhea is caused by the hyperactivation of CFTR channel activity in the gastrointestinal tract. CFTR is a validated target for drug development to treat CF, and extensive research has been conducted to develop CFTR inhibitors for therapeutic interventions of secretory diarrhea. The intracellular processing, trafficking, apical membrane localization, and channel function of CFTR are regulated by dynamic protein-protein interactions in a complex network. In this paper, we review the current knowledge of a macromolecular complex of CFTR, Na⁺/H⁺ exchanger regulatory factor 2 (NHERF2), and lysophosphatidic acids (LPA) receptor 2 (LPA₂) at the apical plasma membrane of airway and gut epithelial cells, and discuss its relevance in human physiology and diseases. We also explore the possibilities of targeting this complex to fine tune CFTR channel activity, with a hope to open up new avenues to develop novel therapies for CF and secretory diarrhea.

PMID: 28869532 [PubMed - in process]

Survival comparison of patients with cystic fibrosis in Canada and the USA.

J Paediatr Child Health. 2017 Sep;53(9):922

Authors: Isaacs D

PMID: 28868779 [PubMed - in process]

Successful treatment of three patients with organizing pneumonia associated with rheumatoid arthritis using clarithromycin and prednisolone.

Drug Discov Ther. 2017;11(4):218-222

Authors: Ohe M, Shida H, Horita T, Ito K, Sugiura M, Hattori A, Oku K

Abstract
Macrolides have anti-inflammatory effects and have been used to treat diffuse panbronchiolitis, bronchiectasis, and cystic fibrosis. Lately, several cases of cryptogenic organizing pneumonia (COP) and radiotherapy-related organizing pneumonia (OP) that were successfully treated with macrolides considering their anti-inflammatory effects were reported. We report three cases of OP associated with rheumatoid arthritis (RA) successfully treated with clarithromycin (CAM) and prednisolone (PSL). Case 1: A 70-year-old woman suffering from RA was admitted with cough and severe dyspnea. She was diagnosed with OP associated with RA on the basis of computed tomography (CT) findings and transbronchial lung biopsy results. She was successfully treated with PSL and cyclosporine A. At the exacerbation of OP, she was successfully treated with CAM and PSL. Case 2: A 74-year-old man suffering from COP visited our department with arthralgia and articular swellings. He was diagnosed with RA, which was thought to be associated with OP. He was successfully treated with CAM and PSL. Case 3: A 54-year-old man suffering from RA presented with an exacerbation of arthralgia and articular swellings and cough. He was diagnosed with OP associated with RA on the basis of CT findings. He was successfully treated with CAM and PSL. The present cases suggest that CAM and PSL treatment may be effective in some cases of OP associated with RA.

PMID: 28867755 [PubMed - in process]

Screening for ADHD in adults with cystic fibrosis: Prevalence, health-related quality of life, and adherence.

J Cyst Fibros. 2017 Aug 31;:

Authors: Georgiopoulos AM, Friedman D, Porter EA, Krasner A, Kakarala SP, Glaeser BK, Napoleon SC, Wozniak J

Abstract
BACKGROUND: International guidelines recommend depression and anxiety screening in individuals with cystic fibrosis (CF), but Attention-Deficit Hyperactivity Disorder (ADHD) remains understudied.
METHODS: Adults with CF (n=53) were screened using the Adult ADHD Self-Report Scale-v1.1 Symptom Checklist (ASRS-v1.1), Cystic Fibrosis Questionnaire-Revised (CFQ-R), and a self-report measure of treatment adherence.
RESULTS: Elevated ADHD symptoms on the ASRS-v1.1 screener were reported by 15% of participants. Self-reported adherence, Body Mass Index in kg/m(2) (BMI), and Forced Expiratory Volume in 1 Second, Percent Predicted (FEV1%pred) did not differ between participants with vs. without elevated ADHD scores. Three CFQ-R scales, Physical Functioning, Role Functioning, and Respiratory Symptoms, were significantly lower in participants with elevated ADHD screens (unadjusted p<0.05). This difference remained statistically significant for the Role Functioning and Respiratory Symptoms scales following correction for multiple comparisons.
CONCLUSIONS: The highly specific screening tool ASRS-v1.1 can ascertain previously undetected ADHD symptoms in adults with CF. ADHD was substantially more prevalent than expected in this population. Elevated ASRS-v1.1 screens correlated with poorer Health-Related Quality of Life (HRQoL) in some domains, but not with BMI, FEV1%pred, or self-reported CF treatment adherence. Additional research will elucidate the impact of ADHD and its treatment on HRQoL, CF self-care and health outcomes.

PMID: 28867260 [PubMed - as supplied by publisher]

The quantitative link of lung clearance index to bronchial segments affected by bronchiectasis.

Thorax. 2017 Sep 02;:

Authors: Verbanck S, King GG, Zhou W, Miller A, Thamrin C, Schuermans D, Ilsen B, Ernst CW, de Mey J, Vincken W, Vanderhelst E

Abstract
In adult patients with cystic fibrosis (CF), the lung clearance index (LCI) derived from the multiple breath washout relates to both acinar and conductive ventilation heterogeneity. The latter component predicts an association between LCI and the number of bronchial segments affected by bronchiectasis. Here, we experimentally demonstrated this association in patients with CF, and also examined an ancillary group of patients with non-CF bronchiectasis. We conclude that lung disease severity in terms of number of bronchial segments results in an associated LCI increase, likely constituting a portion of LCI that cannot be reversed by treatment in patients with CF lung disease.

PMID: 28866642 [PubMed - as supplied by publisher]

Sexual and reproductive health care utilization and preferences reported by young women with cystic fibrosis.

J Cyst Fibros. 2017 Aug 30;:

Authors: Kazmerski TM, Sawicki GS, Miller E, Jones KA, Abebe KZ, Tuchman LK, Ladores S, Rubenstein RC, Sagel SD, Weiner DJ, Pilewski JM, Orenstein DM, Borrero S

Abstract
BACKGROUND: This study aimed to describe and compare the sexual and reproductive health (SRH) care utilization among young women with cystic fibrosis (CF) with the general United States (U.S.) population.
METHODS: Women with CF ages 15-24years from five geographically diverse U.S. CF centers participated in a survey investigating SRH. Results were summarized and compared to a nationally representative sample of young women aged 15-24 who participated in the U.S. National Survey of Family Growth (NSFG) using logistic regression to adjust for confounders.
RESULTS: A total of 188 women with CF (19.7±2.7years) completed the survey; data were compared to 1997 NSFG respondents (19.6±0.10years). Women with CF had lower lifetime rates of ever obtaining a Pap smear or pelvic exam (26% vs. 57%; p<0.001) and similar rates of HPV vaccination (44% vs. 43%; p=0.64) compared to NSFG respondents. Thirty-seven percent of women with CF reported seeking contraception and <10% reported contraceptive counseling, STI testing/counseling, or pregnancy testing in their lifetime. In the prior 12months, 41% of NSFG respondents reported seeking contraception, 24% received contraceptive counseling, 22% STI testing/counseling, and 23% pregnancy testing. A minority of women with CF received or discussed SRH care in the CF setting, although 66% wanted to discuss SRH with their CF team.
CONCLUSIONS: Young women with CF report low rates of SRH care utilization and desire SRH discussions in the CF setting. Interventions should target improved SRH care delivery and encourage patient-provider communication around SRH in the CF care setting.

PMID: 28866451 [PubMed - as supplied by publisher]

CFTR structure.

J Cyst Fibros. 2017 Aug 30;:

Authors: Callebaut I, Chong PA, Forman-Kay JD

Abstract
Structural studies of the cystic fibrosis transmembrane conductance regulator (CFTR) protein are critical to understand molecular mechanisms involved in gating of the apical anion channel as well as the way in which the gating is regulated, especially by the regulatory region (R region). They are also instrumental for understanding the root cause of cystic fibrosis (CF) and supporting the development of therapeutic strategies. In this short review, we summarize recent progress in the knowledge of the CFTR 3D structure and briefly discuss implications for CF drug development.

PMID: 28866450 [PubMed - as supplied by publisher]

Take it to the Bank.

J Cyst Fibros. 2017 Sep;16(5):532-533

Authors: Clancy JP, Joseloff E

PMID: 28865769 [PubMed - in process]

A first step to STOP cystic fibrosis exacerbations.

J Cyst Fibros. 2017 Sep;16(5):529-531

Authors: Burgel PR, Reid DW, Aaron SD

PMID: 28865768 [PubMed - in process]

Invasive Pulmonary Fungal Infections in Cystic Fibrosis.

Mycopathologia. 2017 Sep 01;:

Authors: Schwarz C, Brandt C, Whitaker P, Sutharsan S, Skopnik H, Gartner S, Smazny C, Röhmel JF

Abstract
Invasive pulmonary mycosis is after allergic bronchopulmonary aspergillosis (ABPA) a frequent and severe complication of CF lung disease. Among CF caregivers, there is an insecurity when and how to treat infections of the lung parenchyma caused by different fungi in patients with CF. This case series provides a multicenter experience on diagnostic, manifestation, and treatment of non-ABPA cases of pulmonary. Non-ABPA cases of pulmonary mycoses in patients with CF have been collected from the CF Centers in Berlin, Essen, Worms, Frankfurt (Germany), Leeds (UK), and Barcelona (Spain). Non-ABPA was defined as total serum IgE level <500 kU/L. Scedosporium and Lomentospora species seem to be more virulent in patients with CF and have been successfully treated with triple antifungal drug regimens in several cases. Rare fungi including yeasts can have pathogenic potential in CF. In this series, antibiotic treatment failure was the main indicator for the initiation of antifungal treatment. For an early and effective treatment of pulmonary mycoses in CF, the identification of biomarkers and of risk factors beyond antibiotic treatment failure is crucial and urgently needed. Furthermore, treatment efficacy studies are necessary for the different causative agents of these infections.

PMID: 28864921 [PubMed - as supplied by publisher]