Impact of human mesenchymal stromal cells on antifungal host response against Aspergillus fumigatus.

Oncotarget. 2017 Nov 10;8(56):95495-95503

Authors: Schmidt S, Tramsen L, Schneider A, Schubert R, Balan A, Degistirici Ö, Meisel R, Lehrnbecher T

Abstract
Mesenchymal stromal cells (MSCs) are increasingly given as immunotherapy to hematopoietic stem cell transplant (HSCT) recipients with refractory graft-versus-host disease (GvHD). Whereas the immunosuppressive properties of MSCs seem to be beneficial in GvHD, there is, at the same time, major concern that MSCs increase the risk for infection. We therefore investigated the interplay of human MSCs with Aspergillus fumigatus and the impact of MSCs on different arms of the anti-Aspergillus host response in vitro. Although A. fumigatus hyphae increase mRNA levels of IL6 in MSCs, the extracellular availability of IL-6 and other pro-inflammatory cytokines remains unaffected. Human MSCs are able to phagocyte Aspergillus conidia, but phagocytosis of conidia is not associated with an alteration of the cytokine production by MSCs. In addition, human MSCs do not affect activation and function of A. fumigatus specific CD4+ T cells, and MSCs do not negatively impact the oxidative burst activity of phagocytes. Our in vitro data indicate that administration of human MSCs is not associated with a negative impact on the host response against A. fumigatus and that the fungus does not stimulate MSCs to increase the release of those cytokines which play a central role in the pathophysiology of GvHD.

PMID: 29221143 [PubMed]

Risk Factors for Gaps in Care during Transfer from Pediatric to Adult Cystic Fibrosis Programs in the United States.

Ann Am Thorac Soc. 2017 Dec 08;:

Authors: Sawicki GS, Ostrenga J, Petren K, Fink AK, D'Agostino E, Strassle C, Schechter MS, Rosenfeld M

Abstract
RATIONALE: With improved survival into adulthood, the number of dedicated adult cystic fibrosis (CF) care programs has expanded in the US over the past decade. Transfer from pediatric to adult CF programs represents a potential time for lapses in recommended healthcare.
OBJECTIVES: To describe variability in transfer between pediatric and adult CF care programs and to identify factors associated with prolonged gaps in care.
METHODS: Using the US CF Foundation Patient Registry (CFFPR), we identified individuals with CF who transferred care from a pediatric to adult CF care program during 2007-2013. A gap in care was defined as the time in days between the last recorded pediatric encounter and first recorded adult encounter. A hierarchical multivariable regression model was applied to investigate the effect of program and patient-level factors on gaps in care.
RESULTS: There were 1946 individuals at 155 pediatric CF programs who transferred to an adult CF program during the analytic period. The mean age at transfer was 21.1 years old, with 68% transferring care between ages 18-21 years old. The mean gap in care during transfer was 183 days (median: 106 days, range: 2-1,843 days); 47% had a <100 day gap, and 13% had a ≥365 day gap (prolonged gap). Prolonged gaps in care were more likely to occur among those <age 18 [Odds Ratio (OR), 3.33 (2.06, 5.37)] at the time of transfer and those who transferred to an adult program that was in a different city from their pediatric or affiliate program [OR, 2.16 (1.48, 3.17)]. Having any health insurance coverage was associated with decreased likelihood of prolonged gaps (private insurance vs no insurance [OR, 0.15 (0.09, 0.23)] or any government insurance vs no insurance [OR, 0.11 (0.07, 0.18)]). Lung function, nutritional status, and receipt of intravenous antibiotics in the final year of pediatric care were not associated with the length of gap in care during transfer.
CONCLUSIONS: In the US, the majority of individuals transferring from pediatric to adult CF care do so between ages 18-21. A minority had a gap ≥365 days during transfer to adult care, suggesting that most did not have a disruption in recommended quarterly care visits during the transfer period. Risk factors for prolonged gaps in care include younger age at transfer, lack of health insurance, and relocation. Care coordination during transition in CF may minimize lapses in care by identifying and more closely addressing the needs of individuals at highest risk.

PMID: 29220199 [PubMed - as supplied by publisher]

Supportive palliative care should be integrated into routine care for paediatric patients with life-limiting kidney disease.

Acta Paediatr. 2017 Dec 08;:

Authors: Thumfart J, Reindl T, Rheinlaender C, Müller D

Abstract
AIM: Paediatric palliative care is no longer restricted to patients with cancer and has been extended to patients with other chronic conditions, such as cystic fibrosis or neuromuscular disorders. This review focused on the current state of palliative care for children and adolescents with chronic kidney disease (CKD).
METHOD: We assessed the literature on CKD published up to August 2017. All the papers, except one from 1996, were published this century. This review discusses the role that palliative care plays in the process of decision-making and explores the possibilities of implementing palliative care into the routine therapy of affected patients and providing support for their families.
RESULTS: Offering early palliative care as an integral part of the kidney supportive care provided by the nephrology care team is both necessary and feasible for patients with CKD. As a minimum, a specialised palliative care team should be involved in patients with multiple comorbidities, in conservative treatment scenarios and in acute life-threatening complications. Further studies and guidelines are required to improve the care of patients with CKD and their families.
CONCLUSION: Supportive palliative care should be implemented into the routine care of patients with life-limiting kidney disease. This article is protected by copyright. All rights reserved.

PMID: 29220099 [PubMed - as supplied by publisher]

Evaluating Safety Reporting in Paediatric Antibiotic Trials, 2000-2016: A Systematic Review and Meta-Analysis.

Drugs. 2017 Dec 07;:

Authors: Pansa P, Hsia Y, Bielicki J, Lutsar I, Walker AS, Sharland M, Folgori L

Abstract
BACKGROUND: There are very few options to treat multidrug-resistant bacterial infections in children. A major barrier is the duration and complexity of regulatory trials of new antibiotics. Extrapolation of safety data from adult trials could facilitate drug development for children.
OBJECTIVE: We performed a systematic review on the safety of antibiotic clinical trials (CTs) in children (0-18 years) to evaluate the overall quality of safety trials conducted in children and to determine if age-specific adverse events (AEs) could be identified for specific antibiotic classes.
DATA SOURCES: We searched the MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov electronic databases for trials conducted between 2000 and 2016.
STUDY SELECTION: All trials in which safety was declared a primary or secondary endpoint were included. Exclusion criteria were (1) topical or inhalational route of administration; (2) non-infectious conditions; (3) administration for prophylaxis rather than treatment; (4) selected population (i.e. cystic fibrosis, malignancies, HIV and tuberculosis); and (5) design other than randomized controlled trials. Trials reporting data on both adults and children were included only if paediatric results were reported separately.
DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted the data. To assess the quality of published trials, the Extension for harms for Consolidated Standards of Reporting Trials (CONSORT) Statement 2004 was used.
MAIN OUTCOME AND MEASURE: In order to quantitatively assess the rate of developing AEs by drug class, the numbers of overall and body-system-specific AEs were collected for each study arm, and then calculated per single drug class as median and interquartile range (IQR) of the proportions across CTs. The AEs most frequently reported were compared in the meta-analysis by selecting the CTs on the most represented drug classes.
RESULTS: Eighty-three CTs were included, accounting for 27,693 children. Overall, 69.7% of CONSORT items were fully reported. The median proportion of children with any AE was 22.5%, but did not exceed 8% in any single body system. Serious drug-related AEs and drug-related discontinuations were very rare (median 0.3 and 0.9%, respectively). Limitations included the inability to stratify by age group, particularly neonates.
CONCLUSIONS AND RELEVANCE: Overall, AEs in paediatric antibiotic CTs were predictable and class-specific, and no unexpected (age-specific) side effects were identified. Smaller, open-label, dose-finding, high-quality, single-arm pharmacokinetic trials seem potentially sufficient for certain common antibiotic classes, extrapolating well-established safety profiles determined from large adult efficacy trials. This approach could reduce duration and enhance subsequent registration of urgently needed new antibiotics. This will need to be combined with enhanced methods of pharmacovigilance for monitoring of emerging AEs in routine clinical practice.

PMID: 29218501 [PubMed - as supplied by publisher]

The Anaerobically Induced sRNA PaiI Affects Denitrification in Pseudomonas aeruginosa PA14.

Front Microbiol. 2017;8:2312

Authors: Tata M, Amman F, Pawar V, Wolfinger MT, Weiss S, Häussler S, Bläsi U

Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that can thrive by anaerobic respiration in the lungs of cystic fibrosis patients using nitrate as terminal electron acceptor. Here, we report the identification and characterization of the small RNA PaiI in the P. aeruginosa strain 14 (PA14). PaiI is anaerobically induced in the presence of nitrate and depends on the two-component system NarXL. Our studies revealed that PaiI is required for efficient denitrification affecting the conversion of nitrite to nitric oxide. In the absence of PaiI anaerobic growth was impaired on glucose, which can be reconciled with a decreased uptake of the carbon source under these conditions. The importance of PaiI for anaerobic growth is further underlined by the observation that a paiI deletion mutant was impaired in growth in murine tumors.

PMID: 29218039 [PubMed]

Bone Mineral Density in Cystic Fibrosis: Few Concerns: Authors Reply.

Indian Pediatr. 2017 Nov 15;54(11):973-974

Authors: Gupta S, Kabra SK

PMID: 29217810 [PubMed - in process]

Bone Mineral Density in Cystic Fibrosis: Few Concerns.

Indian Pediatr. 2017 Nov 15;54(11):973

Authors: Siddiqui SA

PMID: 29217809 [PubMed - in process]

Light-focusing human micro-lenses derived from zebrafish-like lens cell masses model lens development and drug-induced cataract in vitro.

Development. 2017 Dec 07;:

Authors: Murphy P, Kabir MH, Srivastava T, Mason ME, Dewi CU, Lim S, Yang A, Djordjevic D, Killingsworth MC, Ho JWK, Harman DG, O'Connor MD

Abstract
Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified including drug treatments, age, smoking, and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells. The purified lens cells and micro-lenses display similar morphology, cellular arrangement, mRNA expression and protein expression to human lens cells and lenses. Exposing the micro-lenses to the emergent cystic fibrosis drug Vx-770 reduces micro-lens transparency and focusing ability. These human micro-lenses provide a powerful and large-scale platform for defining molecular disease mechanisms caused by cataract risk factors, for anti-cataract drug screening, and for clinically-relevant toxicity assays.

PMID: 29217756 [PubMed - as supplied by publisher]

Novel magnetic resonance technique for functional imaging of cystic fibrosis lung disease.

Eur Respir J. 2017 Dec;50(6):

Authors: Nyilas S, Bauman G, Sommer G, Stranzinger E, Pusterla O, Frey U, Korten I, Singer F, Casaulta C, Bieri O, Latzin P

Abstract
Lung function tests are commonly used to monitor lung disease in cystic fibrosis (CF). While practical, they cannot locate the exact origin of functional impairment. Contemporary magnetic resonance imaging (MRI) techniques provide information on the location of disease but the need for contrast agents constrains their repeated application. We examined the correlation between functional MRI, performed without administration of contrast agent, and lung clearance index (LCI) from nitrogen multiple-breath washout (N2-MBW).40 children with CF (median (range) age 12.0 (6-18) years) and 12 healthy age-matched controls underwent functional and structural MRI and lung function tests on the same day. Functional MRI provided semiquantitative measures of perfusion (RQ) and ventilation (RFV) impairment as percentages of affected lung volume. Morphological MRI was evaluated using CF-specific scores. LCI measured global ventilation inhomogeneity.MRI detected functional impairment in CF: RFV 19-38% and RQ 16-35%. RFV and RQ correlated strongly with LCI (r=0.76, p<0.0001 and r=0.85, p<0.0001, respectively), as did total morphology score (r=0.81, p<0.0001). All indices differed significantly between patients with CF and healthy controls (p<0.001).Noninvasive functional MRI is a promising method to detect and visualise perfusion and ventilation impairment in CF without the need for contrast agents.

PMID: 29217601 [PubMed - in process]

Mental health literacy among pediatric hospital staff in the United Arab Emirates.

BMC Psychiatry. 2017 Dec 08;17(1):390

Authors: Al-Yateem N, Rossiter R, Robb W, Ahmad A, Elhalik MS, Albloshi S, Slewa-Younan S

Abstract
BACKGROUND: In the United Arab Emirates (UAE) 35% of the population are aged 0-24 years. A significant proportion of these young people are living with chronic conditions (e.g., asthma, type 1 diabetes, cardiac conditions, and genetically-transmitted conditions such as thalassemia and cystic fibrosis). This group has increased vulnerability to developmental delays and mental health problems, and is increasingly coming to the attention of service providers in mainstream schools, primary healthcare centers, and pediatric hospitals. Despite the government directing attention to improving the mental health of the UAE population, there is concern that mental health services are not growing at the rate needed to meet the mental health needs of children and young people with chronic conditions.
METHOD: A cross sectional survey design was used to determine the mental health literacy of nurses and other healthcare professionals working with children with chronic illnesses. Participants completed a culturally-adapted mental health literacy questionnaire comprising three vignettes of fictional characters meeting diagnostic criteria for posttraumatic stress disorder, psychosis, and depression with suicidal thoughts. Participants also completed the Kessler Psychological Distress Scale (K10).
RESULTS: Participants were 317 healthcare professionals from across the UAE. The majority were nurses. Correct identification of the diagnosis for each vignette was limited, with the highest level of accuracy achieved for the psychosis vignette (n = 113, 54.3%). Accurate identification of appropriate evidence-based interventions was also limited. K10 scores indicated 40% of participants had moderate to high levels of psychological distress.
CONCLUSIONS: These findings are concerning and provide important data to inform the development of undergraduate and continuing education programs for nurses. The K10 scores suggest healthcare professionals are under considerable stress, highlighting the need to support healthcare professionals who experience multiple psychosocial stressors.

PMID: 29216871 [PubMed - in process]

The long and winding road: stem cells for cystic fibrosis.

Expert Opin Biol Ther. 2017 Dec 08;:1-12

Authors: Conese M, Beccia E, Castellani S, Di Gioia S, Colombo C, Angiolillo A, Carbone A

Abstract
INTRODUCTION: Cystic fibrosis (CF) is a genetic syndrome with a high mortality rate due to severe lung disease. Despite having several drugs targeting specific mutated CFTR proteins already in clinical trials, new therapies, based on stem cells, are also emerging to treat those patients. Areas covered: The authors review the main sources of stem cells, including embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs), gestational stem cells, and adult stem cells, such as mesenchymal stem cells (MSCs) in the context of CF. Furthermore, they describe the main animal and human models of lung physiology and pathology, involved in the optimization of these stem cell-applied therapies in CF. Expert opinion: ESCs and iPSCs are emerging sources for disease modeling and drug discovery purposes. The allogeneic transplant of healthy MSCs, that acts independently to specific mutations, is under intense scrutiny due to their secretory, immunomodulatory, anti-inflammatory and anti-bacterial properties. The main challenge for future developments will be to get exogenous stem cells into the appropriate lung location, where they can regenerate endogenous stem cells and act as inflammatory modulators. The clinical application of stem cells for the treatment of CF certainly warrants further insight into pre-clinical models, including large animals, organoids, decellularized organs and lung bioengineering.

PMID: 29216777 [PubMed - as supplied by publisher]

Congenital bilateral absence of the vas deferens as an atypical form of cystic fibrosis: reproductive implications and genetic counseling.

Andrology. 2017 Dec 07;:

Authors: de Souza DAS, Faucz FR, Pereira-Ferrari L, Sotomaior VS, Raskin S

Abstract
Congenital bilateral absence of the vas deferens (CBAVD) is found in 1% to 2% of males with infertility and is present in 6% of obstructive azoospermia cases. Nearly 95% of men with cystic fibrosis (CF, an autosomal recessive disorder) have CBAVD. There are genetic links between CBAVD and CF. Some mutations in the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR) can lead to CBAVD as a monosymptomatic form of CF. With the use of assisted reproductive techniques (ART), especially testicular or epididymal sperm aspiration, intracytoplasmic sperm injection, and in vitro fertilization, it is possible that men with CBAVD can produce offspring. Therefore, genetic counseling should be offered to couples undergoing ART to discuss the probability of having offspring that carry CFTR gene mutations. The aim of this review was to present the main cause of CBAVD, to call attention to its implications for assisted reproduction, and to show the importance of genetic counseling for couples where men have CBAVD, as they can have offspring with a lethal disease.

PMID: 29216686 [PubMed - as supplied by publisher]

Staphylococcus aureus impacts Pseudomonas aeruginosa chronic respiratory disease in murine models.

J Infect Dis. 2017 Dec 05;:

Authors: Cigana C, Bianconi I, Baldan R, De Simone M, Riva C, Sipione B, Rossi G, Cirillo DM, Bragonzi A

Abstract
Background: Staphylococcus aureus and Pseudomonas aeruginosa are key bacterial pathogens of the respiratory tract in patients with cystic fibrosis (CF). While P. aeruginosa chronic bronchial infection is associated with a poorer prognosis, the consequences of S. aureus colonization on CF outcomes are controversial.
Methods: In this paper, murine models of infection resembling traits of the CF human airways disease have been revisited using an infection schedule that mimics the sequence of events of pulmonary disease in CF patients. First, mice were infected with S. aureus, embedded in agar beads; this was followed by P. aeruginosa infection and analysis of bacterial load, leukocyte infiltration, and lung tissue damage.
Results: We reveal that: i) S. aureus promotes severe lesions including abscess formation, ii) S. aureus increases the risk of subsequent chronic P. aeruginosa respiratory infection, iii) once the chronic infection has been established, P. aeruginosa influences most of the inflammatory responses independent of S. aureus.
Conclusions: Our findings established the significance of S. aureus colonization per se and the impact on the subsequent P. aeruginosa infection. This would point towards a thorough assessment for the need of treatment against S. aureus.

PMID: 29216403 [PubMed - as supplied by publisher]

Functional lung MRI for regional monitoring of patients with cystic fibrosis.

PLoS One. 2017;12(12):e0187483

Authors: Kaireit TF, Sorrentino SA, Renne J, Schoenfeld C, Voskrebenzev A, Gutberlet M, Schulz A, Jakob PM, Hansen G, Wacker F, Welte T, Tümmler B, Vogel-Claussen J

Abstract
PURPOSE: To test quantitative functional lung MRI techniques in young adults with cystic fibrosis (CF) compared to healthy volunteers and to monitor immediate treatment effects of a single inhalation of hypertonic saline in comparison to clinical routine pulmonary function tests.
MATERIALS AND METHODS: Sixteen clinically stable CF patients and 12 healthy volunteers prospectively underwent two functional lung MRI scans and pulmonary function tests before and 2h after a single treatment of inhaled hypertonic saline or without any treatment. MRI-derived oxygen enhanced T1 relaxation measurements, fractional ventilation, first-pass perfusion parameters and a morpho-functional CF-MRI score were acquired.
RESULTS: Compared to healthy controls functional lung MRI detected and quantified significantly increased ventilation heterogeneity in CF patients. Regional functional lung MRI measures of ventilation and perfusion as well as the CF-MRI score and pulmonary function tests could not detect a significant treatment effect two hours after a single treatment with hypertonic saline in young adults with CF (p>0.05).
CONCLUSION: This study shows the feasibility of functional lung MRI as a non-invasive, radiation-free tool for monitoring patients with CF.

PMID: 29216201 [PubMed - in process]

The two faces of enhanced stroma: Stroma acts as a tumor promoter and a steric obstacle.

NMR Biomed. 2017 Dec 07;:

Authors: Mierke CT, Sauer F, Grosser S, Puder S, Fischer T, Käs JA

Abstract
In addition to genetic, morphological and biochemical alterations in cells, a key feature of the malignant progression of cancer is the stroma, including cancer cell motility as well as the emergence of metastases. Our current knowledge with regard to the biophysically driven experimental approaches of cancer progression indicates that mechanical aberrations are major contributors to the malignant progression of cancer. In particular, the mechanical probing of the stroma is of great interest. However, the impact of the tumor stroma on cellular motility, and hence the metastatic cascade leading to the malignant progression of cancer, is controversial as there are two different and opposing effects within the stroma. On the one hand, the stroma can promote and enhance the proliferation, survival and migration of cancer cells through mechanotransduction processes evoked by fiber alignment as a result of increased stroma rigidity. This enables all types of cancer to overcome restrictive biological capabilities. On the other hand, as a result of its structural constraints, the stroma acts as a steric obstacle for cancer cell motility in dense three-dimensional extracellular matrices, when the pore size is smaller than the cell's nucleus. The mechanical properties of the stroma, such as the tissue matrix stiffness and the entire architectural network of the stroma, are the major players in providing the optimal environment for cancer cell migration. Thus, biophysical methods determining the mechanical properties of the stroma, such as magnetic resonance elastography, are critical for the diagnosis and prediction of early cancer stages. Fibrogenesis and cancer are tightly connected, as there is an elevated risk of cancer on cystic fibrosis or, subsequently, cirrhosis. This also applies to the subsequent metastatic process.

PMID: 29215759 [PubMed - as supplied by publisher]

Pancreatic Insufficiency in Cystic Fibrosis: Influence of Inflammatory Response Genes.

Pancreas. 2017 Dec 05;:

Authors: Marson FAL, Bertuzzo CS, de Araujo TK, Hortencio TDR, Ribeiro AF, Ribeiro JD

Abstract
OBJECTIVE: Pancreatic insufficiency (PI) in cystic fibrosis (CF) patients is a crucial clinical marker for severity and disease progression. In our study, 125 modifier genes and their SNPs were associated between CF patients with PI or pancreatic sufficiency.
METHODS: We prospectively evaluated 214 CF patients admitted at 1 hospital for a 2-year period. The PI status was associated with clinical variables and SNPs related with inflammatory response considering CFTR mutations. Open Array technique was used to perform the SNPs identification.
RESULTS: For PI risk, after correction by multiple test, in CF patients and 2 CFTR mutations class I, II, and/or III, there were 6 SNPs with positive association (P < 0.005). The odds ratio amplitude was 0.087 (95% confidence interval [CI], 0.004-0.544) for rs9870255*CG (CTNNB1 gene) to 11.06 (95% CI, 1.746-252.3) for rs729302*AA (IRF5 gene). For all CF patients at the same time, 9 SNPs showed positive association. The odds ratio amplitude was 0.144 (95% CI, 0.028-0.602) for rs2348071*AA (PSMA3 gene) to 5.809 (95% CI, 1.536-37.54) for rs11702779*AA (RUNX1 gene). In our data, we observed the interaction between CFTR mutations, rs9870255*CTNNB1, rs9378805*IRF4, and rs7664617*KCNIP4 to PI status.
CONCLUSIONS: Multiple SNPs in inflammatory response genes showed association with PI considering the CFTR mutations screening.

PMID: 29215541 [PubMed - as supplied by publisher]

Epidemiology of Rare Lung Diseases: The Challenges and Opportunities to Improve Research and Knowledge.

Adv Exp Med Biol. 2017;1031:419-442

Authors: McCarthy C, Lara Gallego B, Trapnell BC, McCormack FX

Abstract
Rare lung diseases encompass a broad spectrum of conditions and affect an estimated 1.2-2.5 million people in North America and 1.5-3 million people in Europe. While individual rare lung diseases affect less than 1 in 2000 individuals, collectively they have a significant impact upon the population at large. Hence it is vital to understand firstly the epidemiology and subsequently the pathogenesis and clinical course of these disorders. Through a greater understanding of these aspects of disease, progress can be made in reducing symptoms, containing healthcare costs and utilizing resources efficiently. Furthermore, a greater understanding of the pathobiology of rare lung diseases can inform both the pathogenesis and management of more common pulmonary disorders.In this chapter we review how epidemiological approaches and the utilization of patient registries has improved the knowledge and management of rare lung diseases. We further focus on the epidemiology of several of the more widely known rare pulmonary disorders, including idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF) and alpha-1 antitrypsin deficiency (AATD). To conclude we describe how patient advocacy groups and foundations have driven advances in research and management of ultra-rare lung diseases, namely, the major strides made in the management and understanding of lymphangioleiomyomatosis (LAM) and pulmonary alveolar proteinosis (PAP).We conclude that the models used to study some of the rarest of diseases may be successfully adopted by other rare and common disease communities, leading to improved care and the possibility of novel therapeutic options.

PMID: 29214586 [PubMed - in process]

Is bronchoscopy an obsolete tool in cystic fibrosis? The role of bronchoscopy in cystic fibrosis and its clinical use.

J Thorac Dis. 2017 Sep;9(Suppl 10):S1139-S1145

Authors: Paul L

Abstract
Cystic fibrosis (CF) is a progressive life threatening multisystem genetic disease which affects the CF transmembrane conductance regulator channel. Respiratory causes remain the most common mortality in CF. With the onset of newborn screening, initiating treatments both for prophylaxis and disease management, optimizing nutritional support, and developing therapies targeting CF transmembrane conductance regulator protein, this has significantly changed the face of managing this devastating disease. Bronchoscopy and related procedures such as bronchoalveolar lavage (BAL), transbronchial biopsies, and protected brush sampling have been looked at in the management of CF as patients with CF continue to live longer with the help of newer therapies, the microbiome in the lung becomes less diverse along with increased occurrences for noninfectious causes of airway diseases. Though bronchoscopy has been used in conjunction with other modalities such as computed tomography and sputum induction providing a better understanding of the progression of the disease, it still remains valuable in the diagnosis and management of CF.

PMID: 29214071 [PubMed]

Identification of the lipid biomarkers from plasma in idiopathic pulmonary fibrosis by Lipidomics.

BMC Pulm Med. 2017 Dec 06;17(1):174

Authors: Yan F, Wen Z, Wang R, Luo W, Du Y, Wang W, Chen X

Abstract
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an irreversible interstitial pulmonary disease featured by high mortality, chronic and progressive course, and poor prognosis with unclear etiology. Currently, more studies have been focusing on identifying biomarkers to predict the progression of IPF, such as genes, proteins, and lipids. Lipids comprise diverse classes of molecules and play a critical role in cellular energy storage, structure, and signaling. The role of lipids in respiratory diseases, including cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD) has been investigated intensely in the recent years. The human serum lipid profiles in IPF patients however, have not been thoroughly understood and it will be very helpful if there are available molecular biomarkers, which can be used to monitor the disease progression or provide prognostic information for IPF disease.
METHODS: In this study, we performed the ultraperformance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) to detect the lipid variation and identify biomarker in plasma of IPF patients. The plasma were from 22 IPF patients before received treatment and 18 controls.
RESULTS: A total of 507 individual blood lipid species were determined with lipidomics from the 40 plasma samples including 20 types of fatty acid, 159 types of glycerolipids, 221 types of glycerophospholipids, 47 types of sphingolipids, 46 types of sterol lipids, 7 types of prenol lipids, 3 types of saccharolipids, and 4 types of polyketides. By comparing the variations in the lipid metabolite levels in IPF patients, a total of 62 unique lipids were identified by statistical analysis including 24 kinds of glycerophoslipids, 30 kinds of glycerolipids, 3 kinds of sterol lipids, 4 kinds of sphingolipids and 1 kind of fatty acids. Finally, 6 out of 62 discriminating lipids were selected as the potential biomarkers, which are able to differentiate between IPF disease and controls with ROC analysis.
CONCLUSIONS: Our results provided vital information regarding lipid metabolism in IPF patients and more importantly, a few potentially promising biomarkers were firstly identified which may have a predictive role in monitoring and diagnosing IPF disease.

PMID: 29212488 [PubMed - in process]

Ion channels of the lung and their role in disease pathogenesis.

Am J Physiol Lung Cell Mol Physiol. 2017 Nov 01;313(5):L859-L872

Authors: Bartoszewski R, Matalon S, Collawn JF

Abstract
Maintenance of normal epithelial ion and water transport in the lungs includes providing a thin layer of surface liquid that coats the conducting airways. This airway surface liquid is critical for normal lung function in a number of ways but, perhaps most importantly, is required for normal mucociliary clearance and bacterial removal. Preservation of the appropriate level of hydration, pH, and viscosity for the airway surface liquid requires the proper regulation and function of a battery of different types of ion channels and transporters. Here we discuss how alterations in ion channel/transporter function often lead to lung pathologies.

PMID: 29025712 [PubMed - indexed for MEDLINE]