Erratum: Epidemiology of Pulmonary Nontuberculous Mycobacterial Sputum Positivity in Patients with Cystic Fibrosis in the United States, 2010-2014.

Ann Am Thorac Soc. 2018 Sep;15(9):1114-1115

Authors:

PMID: 30907110 [PubMed - in process]

Lung Transplantation as Successful Treatment of End-stage Idiopathic Pleuroparenchymal Fibroelastosis: A Case Report.

Transplant Proc. 2019 Jan - Feb;51(1):235-238

Authors: Righi I, Morlacchi L, Rossetti V, Mendogni P, Palleschi A, Tosi D, Pieropan S, Del Gobbo A, Nosotti M

Abstract
Pleuroparenchymal fibroelastosis (PPFE) is a rare condition, characterized by predominantly upper-lobe pleural and subjacent parenchymal fibrosis, the latter being intra-alveolar with accompanying elastosis of the alveolar walls that leads a clinical progression to respiratory failure. This condition may not be as rare as it seems to be, because nowadays the increasing awareness among specialists is raising the number of new diagnoses. Limited data are available about the prognosis, both for secondary and idiopathic forms. Nevertheless, the idiopathic form seems to be rapidly progressive and no treatment can control the disease, which is why management is challenging. Since the disease was characterized, PPFE cases have been reported in the literature, but most have been secondary rather than idiopathic. Of these, few have successfully undergone lung transplantation as a treatment of end-stage respiratory failure. We here report a successful case of a 38-year-old man affected by idiopathic PPFE who underwent bilateral lung transplantation after extracorporeal membrane oxygenation bridging for an abrupt transition to critical clinical conditions. After a complex postoperative course and a first year characterized by acute rejection, the patient is alive at 5 years with a good quality of life. Our experience confirms that lung transplantation would be a valuable treatment option in case of end-stage idiopathic PPFE cases.

PMID: 30655147 [PubMed - indexed for MEDLINE]

Surveillance Transbronchial Biopsy Program to Evaluate Acute Rejection After Lung Transplantation: A Single Institution Experience.

Transplant Proc. 2019 Jan - Feb;51(1):198-201

Authors: Tosi D, Carrinola R, Morlacchi LC, Tarsia P, Rossetti V, Mendogni P, Rosso L, Righi I, Damarco F, Nosotti M

Abstract
BACKGROUND: There is no unanimity in the literature regarding the value of transbronchial biopsies (TBBs) performed at a scheduled time after lung transplantation (surveillance TBBs [SBs]), compared to biopsies performed for suspected clinical acute rejection (clinically indicated TBBs [CIBs]). This study exposes an assessment of our experience over the last 4 years through a retrospective analysis of the data collected.
METHODS: In our center, SBs are performed at 3, 6, and 12 months after a transplant. Data from 110 patients who underwent a TBB were collected from January 2013 to November 2017. Clinical and functional data along with the histologic results and complications were collected.
RESULTS: Overall 251 procedures were performed: 223 for surveillance purposes and 28 for clinical indications. The SBs diagnostic rate was 84%. A grade 2 acute rejection (AR) was detected in 9 asymptomatic patients, all of whom were medically treated, with downgrading of AR documented in all cases. The rate of medical intervention in the SB group was 8%. The CIBs diagnostic rate was 96%. The rate of AR detected by CIBs was significantly higher than by SBs (36% versus 4%; P < .0001). Overall the major complication rate was 4%; no patients required transfusions and no mortality occurred in the patient cohort.
CONCLUSIONS: The surveillance protocol did not eliminate the necessity of CIBs, but in 8% of patients early rejection was histologically assessed. The correlation between histologic and clinical data allows a more careful approach to transplanted patients.

PMID: 30655138 [PubMed - indexed for MEDLINE]

Clinical Application of Polysialylated Deoxyribonuclease and Erythropoietin.

Recent Pat Drug Deliv Formul. 2018;12(3):212-222

Authors: Meng H, Jain S, Lockshin C, Shaligram U, Martinez J, Genkin D, Hill DB, Ehre C, Clark D, Hoppe Iv H

Abstract
BACKGROUND: While protein therapeutics are invaluable in managing numerous diseases, many require frequent injections to maintain therapeutically effective concentrations, due to their short half-life in circulation. PolyXen™, a platform and patented technology employing biodegradable, non-immunogenic and hydrophilic Polysialic Acids (PSA) for drug delivery, is being utilized to overcome such limitations, thereby potentially enabling the clinical utility of a broad range of protein therapeutics. Here, we report the recent progress on two development candidates, polysialylated deoxyribonuclease I (PSA-DNase) and polysialylated erythropoietin (PSA-EPO).
METHODS AND RESULTS: Chemical polysialylation of DNase I (DNase) using PSA with different chain length at various conjugation sites led to improved stability against proteases and thermal stress, and slightly reduced enzymatic activity. Polysialylation of EPO resulted in retention of protein structure and PSA-EPO remained biologically active. PSA-EPO had a significantly prolonged circulating half-life (e.g. t1/2 of PSA-EPO = ~400 h in patients after subcutaneous administration, aimed for once monthly administration, vs. t1/2 of EPO = ~22 h; administered twice or thrice weekly), and retained in vivo efficacy.
CONCLUSION: This approach has been clinically validated in phase I (in healthy volunteers) and II studies of PSA-EPO [for managing anemia in patients with chronic kidney disease (CKD)].

PMID: 30019653 [PubMed - indexed for MEDLINE]

Cystic fibrosis in the modern therapeutic era: Give the shower a thought!

J Cyst Fibros. 2019 Mar 20;:

Authors: Le Pennec D, Baravalle-Einaudi M, Dupont C, Vecellio L, Dubus JC, GRAM (Aerosols and Cystic Fibrosis Workgroup of the French Cystic Fibrosis Society)

Abstract
Fifty-two meshes of e-flow rapid® were characterized for tobramycin delivery with a laser diffractometer after 6 months of home use by cystic fibrosis patients treated with various nebulized drugs. Three meshes were out of order and 30 considered to be defective for tobramycin delivery. The use of the specific mesh cleaning shower system permitted 14 defective meshes to be in the expected range of nebulized volume.

PMID: 30904464 [PubMed - as supplied by publisher]

Interactions of an Emerging Fungal Pathogen Scedosporium aurantiacum with Human Lung Epithelial Cells.

Sci Rep. 2019 Mar 22;9(1):5035

Authors: Kaur J, Kautto L, Penesyan A, Meyer W, Elbourne LDH, Paulsen IT, Nevalainen H

Abstract
Scedosporium fungi are found in various natural and host-associated environments, including the lungs of cystic fibrosis patients. However, their role in infection development remains underexplored. Here the attachment of conidia of a virulent S. aurantiacum strain WM 06.482 onto the human lung epithelial A549 cells in vitro was visualized using microscopy to examine the initial steps of infection. We showed that 75-80% of fungal conidia were bound to the A549 cells within four hours of co-incubation, and started to produce germ tubes. The germinating conidia seemed to invade the cells through the intercellular space, no intracellular uptake of fungal conidia by the airway epithelial cells after conidial attachment. Transcriptomic analysis of the A549 cells revealed that the up-regulated genes were mainly associated with cell repair and inflammatory processes indicating a protective response against S. aurantiacum infection. Network analysis of the differentially expressed genes showed activation of the innate immune system (NF-kB pathway) leading to the release of pro-inflammatory cytokines. We believe this is the first report showing the transcriptomic response of human alveolar epithelial cells exposed to S. aurantiacum conidia paving a way for better understanding of the mechanism of the infection process.

PMID: 30903006 [PubMed - in process]

Exercise as a therapeutic intervention for people with cystic fibrosis.

Expert Rev Respir Med. 2019 Mar 22;:

Authors: Ward N, Stiller K, Holland AE

Abstract
INTRODUCTION: The complex multisystem nature of cystic fibrosis (CF) commonly results in reduced exercise tolerance, which is independently associated with poor clinical outcomes. Exercise is routinely recommended as part of the therapeutic regimen in CF to improve both respiratory and non-respiratory impairments. Areas covered: This article summarises the most recent evidence regarding the use of exercise as a therapeutic intervention in CF and discusses some of the practical considerations for exercise prescription in this setting. Clinical trials in progress and future research priorities are outlined. Expert opinion: On the balance of available evidence, exercise is likely to assist in improving physical fitness and health-related quality of life (HRQOL) and may be associated with a slower rate of decline in respiratory function in CF. Limitations to current studies include small sample sizes, study durations insufficient to achieve a training effect and difficulty distinguishing the effects of exercise training from that of other interventions implemented as part of a package of care. Larger, multi-centred trials are required to clarify the role of exercise in CF in improving physical fitness, respiratory function, HRQOL, as a substitute for traditional airway clearance techniques and in the management of common CF-related comorbidities.

PMID: 30902029 [PubMed - as supplied by publisher]

Methicillin-resistant Staphylococcus aureus eradication in cystic fibrosis patients: A randomized multicenter study.

PLoS One. 2019;14(3):e0213497

Authors: Dolce D, Neri S, Grisotto L, Campana S, Ravenni N, Miselli F, Camera E, Zavataro L, Braggion C, Fiscarelli EV, Lucidi V, Cariani L, Girelli D, Faelli N, Colombo C, Lucanto C, Lombardo M, Magazzù G, Tosco A, Raia V, Manara S, Pasolli E, Armanini F, Segata N, Biggeri A, Taccetti G

Abstract
BACKGROUND: Few studies, based on a limited number of patients using non-uniform therapeutic protocols, have analyzed Methicillin-resistant Staphylococcus aureus (MRSA) eradication.
METHODS: In a randomized multicenter trial conducted on patients with new-onset MRSA infection we evaluated the efficacy of an early eradication treatment (arm A) compared with an observational group (B). Arm A received oral rifampicin and trimethoprim/sulfamethoxazole (21 days). Patients' microbiological status, FEV1, BMI, pulmonary exacerbations and use of antibiotics were assessed.
RESULTS: Sixty-one patients were randomized. Twenty-nine (47.5%) patients were assigned to active arm A and 32 (52.5%) patients to observational arm B. Twenty-nine (47.5%) patients, 10 patients in arm A and 19 in arm B, dropped out of the study. At 6 months MRSA was eradicated in 12 (63.2%) out of 19 patients in arm A while spontaneous clearance was observed in 5 (38.5%) out of 13 patients in arm B. A per-protocol analysis showed a 24.7% difference in the proportion of MRSA clearance between the two groups (z = 1.37, P(Z>z) = 0.08). Twenty-seven patients, 15 (78.9%) out of 19 in arm A and 12 (92.3%) out of 13 in arm B, were able to perform spirometry. The mean (±SD) FEV1 change from baseline was 7.13% (±14.92) in arm A and -1.16% (±5.25) in arm B (p = 0.08). In the same period the BMI change (mean ±SD) from baseline was 0.54 (±1.33) kg/m2 in arm A and -0.38 (±1.56) kg/m2 in arm B (p = 0.08). At 6 months no statistically significant differences regarding the number of pulmonary exacerbations, days spent in hospital and use of antibiotics were observed between the two arms.
CONCLUSIONS: Although the statistical power of the study is limited, we found a 24.7% higher clearance of MRSA in the active arm than in the observational arm at 6 months. Patients in the active arm A also had favorable FEV1 and BMI tendencies.

PMID: 30901344 [PubMed - in process]

Tailored nanocarriers for the pulmonary delivery of levofloxacin against Pseudomonas aeruginosa: a comparative study.

Mol Pharm. 2019 Mar 22;:

Authors: Derbali RM, Aoun V, Moussa G, Frei G, F Tehrani S, Campos Del'Orto J, Hildgen P, Roullin VG, Leblond Chain J

Abstract
Cystic fibrosis (CF) patients are faced with chronic bacterial infections displaying persistent resistance if not eradicated during the first stage of the disease. Nanoantibiotics for pulmonary administration, such as liposomal ciprofloxacin or amikacin, have progressed through clinics thanks to their sustained release, prolonged lung residence time and low systemic absorption. In this work, we sought a nanoformulation of levofloxacin for the treatment of Pseudomonas aeruginosa. We prepared and compared PLA-g-PEG nanoparticles, as well as anionic and cationic liposomes for their size, charge and encapsulation efficiency. Cationic liposomes were unable to encapsulate any drug and were subsequently considered as a control formulation. Regarding the efficiency of the nanocarrier, anionic liposomes exhibited a prolonged release over 72 h and preserved the antibacterial activity of levofloxacin against 5 strains of Pseudomonas aeruginosa, whereas polymeric nanoparticles quickly released their entire payload and increased the minimal inhibitory concentration (MIC) of levofloxacin. Thus, only anionic liposomes were considered for further preclinical development. Anionic liposomes exhibited a suitable colloidal stability by Turbiscan analysis and crossed a layer of artificial mucus in under one hour in a Transwell setup. Despite their negative surface charge, liposomes still interacted with P. aeruginosa membrane in a dose-reponse manner, as demonstrated by flow cytometry. Viability assays confirmed that anionic liposomes, loaded or not, exhibited a good safety profile on A549 epithelial cells even at high concentrations. Finally, nebulization of anionic liposomes containing levofloxacin did not impact their colloidal stability and the droplet size distribution was suitable for deep lung deposition, where P. aeruginosa infection lies. Therefore, levofloxacin-loaded anionic liposomes exhibited suitable properties for the pulmonary treatment of P. aeruginosa in CF. This step-by-step study confirms the promising role of liposomes for lung administration of antibiotics, as recently seen in clinics, and fosters their development for several types of antibiotics.

PMID: 30900903 [PubMed - as supplied by publisher]

Isolation of Aggregatibacter aphrophilus from bronchoalveolar lavage in a paediatric patient presenting with haemoptysis.

New Microbes New Infect. 2019 May;29:100509

Authors: Patas K, Douros K, Priftis KN, Ioannidis A, Nikolaou C, Chatzipanagiotou S

Abstract
We report a rare case of non-cystic fibrosis bronchiectasis accompanied by protracted infection with Aggregatibacter aphrophilus in a 12-year-old boy with haemoptysis.

PMID: 30899518 [PubMed]

The gliadin-CFTR connection: new perspectives for the treatment of celiac disease.

Ital J Pediatr. 2019 Mar 21;45(1):40

Authors: Maiuri L, Villella VR, Raia V, Kroemer G

Abstract
Familial loss-of-function mutations of the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) channel protein cause cystic fibrosis (CF), the most frequent inherited life-threatening disease in the Caucasian population. A recent study indicates that the gluten/gliadin-derived peptide (P31-43) can cause CFTR inhibition in intestinal epithelial cells, thus causing a local stress response that contributes to the immunopathology of celiac disease (CD). Accordingly, an increased prevalence of CD has been observed in several cohorts of CF patients. CD is characterized by a permanent intolerance to gluten/gliadin proteins occurring in a proportion of susceptible individuals who bear the human leukocyte antigen (HLA) DQ2/DQ8. In CD, perturbations of the intestinal environment, together with the activation of the innate immune system by P31-43, are essential for rendering other immunodominant gliadin peptide fully antigenic, thus triggering an adaptive immune response with an autoimmune component. P31-43-induced CFTR inhibition elicits the danger signals that ignite the epithelial stress response and perturb epithelial proteostasis. Importantly, potentiators of CFTR channel gating, such as the FDA-approved drug Ivacaftor, prevent P31-43 driven CFTR inhibition and suppress the gliadin-induced stress response in cells from celiac patients, as well as the immunopathology developing in gliadin-sensitive mice. Thus, CFTR potentiators may represent a novel therapeutic option for celiac patients.

PMID: 30898172 [PubMed - in process]

Spectrum of CFTR mutations in Chechen cystic fibrosis patients: high frequency of c.1545_1546delTA (p.Tyr515X; 1677delTA) and c.274G>A (p.Glu92Lys, E92K) mutations in North Caucasus.

BMC Med Genet. 2019 Mar 21;20(1):44

Authors: Petrova NV, Kashirskaya NY, Saydaeva DK, Polyakov AV, Adyan TA, Simonova OI, Gorinova YV, Kondratyeva EI, Sherman VD, Novoselova OG, Vasilyeva TA, Marakhonov AV, Macek M, Ginter EK, Zinchenko RA

Abstract
BACKGROUND: Cystic fibrosis (CF; OMIM #219700) is a common autosomal recessive disease caused by pathogenic variants (henceforward mutations) in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The spectrum and frequencies of CFTR mutations vary among different populations. Characterization of the specific distribution of CFTR mutations can be used to optimize genetic counseling, foster reproductive choices, and facilitate the introduction of mutation-specific therapies. Chechens are a distinct Caucasian ethnic group of the Nakh peoples that originated from the North Caucasus. Chechens are one of the oldest ethnic groups in the Caucasus, the sixth largest ethnic group in the Russian Federation (RF), and constitute the majority population of the Chechen Republic (Chechnya). The spectrum of CFTR mutations in a representative cohort of Chechen CF patients and healthy individuals was analyzed.
METHODS: Molecular genetic analysis of 34 CFTR mutations (representing approx. 80-85% of mutations in multiethnic CF populations of the RF) was performed in 32 CF patients from 31 unrelated Chechen families living in Chechnya. One hundred randomly chosen healthy Chechens were analyzed for the 15 most common "Russian" mutations. The clinical symptoms in Chechen CF patients with different CFTR genotypes were investigated.
RESULTS: High frequencies of c.1545_1546delTA (p.Tyr515X; 1677delTA) (52 out of 64 CFTR alleles tested; 81.3%) and c.274G > A (p.Glu92Lys, E92K) (8/64, 12.5%) mutations were found. Twenty patients were homozygous for the c.1545_1546delTA mutation, and eight were compound heterozygous for the c.1545_1546delTA and c.274G > A mutations. Three carriers of the c.1545_1546delTA mutation were also found in the cohort of 100 apparently healthy Chechens (frequency - 0.015). The c.1545_1546delTA and c.274G > A mutations are linked to the same haplotype (22-7-16-13) of intragenic Short Tandem Repeat markers, i.e., IVS1CA, IVS6aGATT, IVS8CA, and IVS17bCA.
CONCLUSIONS: The distribution of CFTR mutations in the Chechen CF population is unique regarding the high frequency of mutations c.1545_1546delTA and c.274G > A (more than 90% of the mutant alleles). The c.274G > A mutation is associated with a less severe course of CF than that observed in c.1545_1546delTA homozygotes. Testing for these two variants can be proposed as the first step of CF DNA diagnosis in the Chechen population.

PMID: 30898088 [PubMed - in process]

Brevenal, a Marine Natural Product, is Anti-Inflammatory and an Immunomodulator of Macrophage and Lung Epithelial Cells.

Mar Drugs. 2019 Mar 20;17(3):

Authors: Keeler DM, Grandal MK, McCall JR

Abstract
Chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), cystic fibrosis, and asthma, are some of the leading causes of illness and fatalities worldwide. The search for novel treatments led to the exploration of marine natural products as drug candidates to combat the debilitating effects of mucus accumulation and chronic inflammation. Previous research showed that an alga-derived compound, brevenal, could attenuate the effects of inflammatory agents, but the mechanisms by which it exerted its effects remained unclear. We investigated the effects of brevenal on lipopolysaccharide (LPS) induced cytokine/chemokine production from murine macrophages and human lung epithelial cells. It was found that brevenal reduces proinflammatory mediator secretion while preserving anti-inflammatory secretion from these cells. Furthermore, we found that brevenal does not alter cell surface Toll-like receptor 4 (TLR4) expression, thereby maintaining the cells' ability to respond to bacterial infection. However, brevenal does alter macrophage activation states, as demonstrated by reduced expression of both M1 and M2 phenotype markers, indicating this putative anti-inflammatory drug shifts innate immune cells to a less active state. Such a mechanism of action would be ideal for reducing inflammation in the lung, especially with patients suffering from chronic respiratory diseases, where inflammation can be lethal.

PMID: 30897777 [PubMed - in process]

Nutritional Treatment of a Young Infant with Cystic Fibrosis Presenting with Severe Kwashiorkor Dermatosis.

J Trop Pediatr. 2019 Mar 20;:

Authors: Sandy NS, Nogueira RJN

Abstract
Kwashiorkor in infancy is typically associated to an underlying disease. Edema, a striking feature of this type of malnutrition, can be difficult to assess in this age group. The typical dermatosis of Kwashiorkor is not fully explained the deficiency of one isolated vitamin or micronutrient. This article presents an infant with cystic fibrosis, who developed Kwashiorkor in the third month of life with extensive cutaneous manifestations. An early, individualized and aggressive nutritional intervention with optimized supplementationof sulfur amino acids, vitamins and micronutrients was established, with impressively recovery of overall nutrition and skin manifestations in a relatively short period of time.

PMID: 30897613 [PubMed - as supplied by publisher]

Tetrafunctional Block Copolymers Promote Lung Gene Transfer in Newborn Piglets.

Mol Ther Nucleic Acids. 2019 Feb 26;16:186-193

Authors: Caballero I, Riou M, Hacquin O, Chevaleyre C, Barc C, Pezant J, Pinard A, Fassy J, Rezzonico R, Mari B, Heuzé-Vourc'h N, Pitard B, Vassaux G

Abstract
Tetrafunctional block copolymers are molecules capable of complexing DNA. Although ineffective in vitro, studies in mice have shown that the tetrafunctional block copolymer 704 is a more efficient lung gene transfer agent than the cationic liposome GL67A, previously used in a phase II clinical trial in cystic fibrosis patients. In the present study, we compared the gene transfer capacity of the 704-DNA formulation and a cationic liposome-DNA formulation equivalent to GL67A in a larger-animal model, the newborn piglet. Our results indicate an efficacy of the 704-DNA formulation well above one order of magnitude higher than that of the cationic liposome-DNA formulation, with no elevated levels of interleukin-6 (IL-6), taken as a marker of inflammation. Transgene expression was heterogeneous within lung lobes, with expression levels that were below the detection threshold in some samples, while high in other samples. This heterogeneity is likely to be due to the bolus injection procedure as well as to the small volume of injection. The present study highlights the potential of tetrafunctional block copolymers as non-viral vectors for lung gene therapy.

PMID: 30897407 [PubMed - as supplied by publisher]

Pharmacotherapeutic strategies for treating bronchiectasis in pediatric patients.

Expert Opin Pharmacother. 2019 Mar 21;:1-12

Authors: Lee E, Hong SJ

Abstract
INTRODUCTION: The social and medical costs of bronchiectasis in children are becoming considerable due to its increasing prevalence. Early identification and intensive treatment of bronchiectasis are needed to decrease the morbidity and mortality associated with bronchiectasis in children. Area covered: This review presents the current pharmacotherapeutic strategies for treating bronchiectasis in children with a focus on non-cystic fibrosis bronchiectasis. Expert opinion: Evidence for the effectiveness of diverse treatment strategies in bronchiectasis is lacking, particularly in children, although the disease burden is substantial for bronchiectasis. Most treatment strategies for non-cystic fibrosis bronchiectasis in children have been extrapolated from those in adults with bronchiectasis or children with cystic fibrosis. Antibiotics combined with an active airway clearance therapy via the inhalation of mucoactive agents can stabilize bronchiectasis. The timely and intensive administration of antibiotics during acute exacerbation of bronchiectasis is essential to prevent its progression in children. To suppress the bacterial loads in the airway, systemic or inhaled antibiotics can be administered intermittently or continuously. However, studies on these protocols, including the appropriate duration and effective dosages are lacking. Long-term administration of azithromycin for 12-24 months may reduce the exacerbation frequency with the increased carriage rate of azithromycin-resistant bacteria.

PMID: 30897021 [PubMed - as supplied by publisher]

Mice with a Deletion of Rsph1 Exhibit a Low Level of Mucociliary Clearance and Develop a PCD Phenotype.

Am J Respir Cell Mol Biol. 2019 Mar 21;:

Authors: Yin W, Livraghi-Butrico A, Sears PR, Rogers TD, Burns KA, Grubb BR, Ostrowski LE

Abstract
Primary ciliary dyskinesia (PCD) is a genetically and phenotypically heterogeneous disease caused by mutations in over 40 different genes. Individuals with PCD caused by mutations in radial spoke head 1 homolog (RSPH1) have been reported to have a milder phenotype compared to other PCD subjects, as evidenced by a lower incidence of neonatal respiratory distress, higher nasal nitric oxide levels, and better lung function. To better understand genotype-phenotype relationships in PCD, we have characterized a mutant mouse model with a deletion of Rsph1. Approximately 50% of cilia from Rsph-/- cells appeared normal by transmission electron microscopy, while the remaining cilia revealed a range of defects, primarily transpositions or a missing central pair. Ciliary beat frequency in Rsph-/- cells was significantly lower than in controls (20.2 + 0.8 vs. 25.0 + 0.9 Hz), and the cilia exhibited an aberrant rotational waveform. Young Rsph-/- animals demonstrated a low rate of mucociliary clearance in the nasopharynx that was reduced to zero by ~1 month of age. Rsph1-/- animals accumulated mucus in the nasal cavity but had a lower bacterial burden than animals with a deletion of dynein axonemal intermediate chain 1 (Dnaic1-/-). Thus, Rsph-/- mice display a similar, but less severe, PCD phenotype to that observed in Dnaic1-/- mice, similar to what has been observed in humans. The results suggest that some individuals with PCD may not have a complete loss of mucociliary clearance, and further suggest that early diagnosis and intervention may be important to maintain this low level of clearance.

PMID: 30896965 [PubMed - as supplied by publisher]

Experience of Using a Semielemental Formula for Home Enteral Nutrition in Children: A Multicenter Cross-sectional Study.

J Pediatr Gastroenterol Nutr. 2019 Apr;68(4):585-590

Authors: Leonard M, Caldari D, Mas E, Lambe C, Comte A, Ley D, Peretti N, Borderon C, Marinier E, Coste ME, Lamireau T, Rubio A, Turquet A, Dubern B, Dabadie A, Gautry J, Kyheng M, Guimber D, Gottrand F

Abstract
OBJECTIVES: The use of semielemental diets concerns a small proportion of children on enteral nutrition whose characteristics have never been reported. Our aim was to describe a cohort of patients on home enteral nutrition with Peptamen Junior, including the tolerance and nutritional efficacy of this product.
METHODS: We performed a retrospective multicenter survey on a cohort of patients receiving this semielemental diet at home between 2010 and 2015 in 14 tertiary pediatric French centers. We recorded at baseline, 3, 6, and 12 months, and then every year the anthropometric characteristics of the patients, indications and modalities of administration of the diet, and the tolerance and adverse events.
RESULTS: We recruited 136 patients ages 9.8 ± 4.4 years at baseline. Mean body mass index z score was -1.0 ± 1.8; mean height z score was -1.1 ± 1.9. The main underlying diseases were digestive (35.3%), neurological (33.1%), and hematological (19.9%). The indications for a semielemental diet were failure of another diet in 70 patients (51.9%), severe malnutrition in 19 (14.1%), cystic fibrosis in 11 (8.1%), and switch from parenteral nutrition in 11 (8.1%). Side effects were observed in 39.2% of the patients, and required medical attention in 8.2%. Body mass index improved or remained normal in 88.3% of children.
CONCLUSIONS: This semielemental diet seems to be well tolerated and efficient in the setting of home enteral nutrition in children with complex diseases featuring malabsorption and/or after failure of polymeric diet.

PMID: 30896609 [PubMed - in process]

Cutaneous small-vessel vasculitis associated with paediatric ulcerative colitis: A case study and literature review.

J Paediatr Child Health. 2019 Mar 20;:

Authors: Romano C, Valenti S, Pidone C, Spina M, Caruso RA, Gallizzi R, Dipasquale V

PMID: 30895688 [PubMed - as supplied by publisher]

In vitro Interactions of Pseudomonas aeruginosa With Scedosporium Species Frequently Associated With Cystic Fibrosis.

Front Microbiol. 2019;10:441

Authors: Homa M, Sándor A, Tóth E, Szebenyi C, Nagy G, Vágvölgyi C, Papp T

Abstract
Members of the Scedosporium apiospermum species complex are the second most frequently isolated pathogens after Aspergillus fumigatus from cystic fibrosis (CF) patients with fungal pulmonary infections. Even so, the main risk factors for the infection are unrevealed. According to previous studies, bacterial infections might reduce the risk of a fungal infection, but an antibacterial therapy may contribute to the airway colonization by several fungal pathogens. Furthermore, corticosteroids, which are often used to reduce lung inflammation in children and adults with CF, are also proved to enhance the growth of A. fumigatus in vitro. Considering all the above discussed points, we aimed to test how Pseudomonas aeruginosa influences the growth of scedosporia and to investigate the potential effect of commonly applied antibacterial agents and corticosteroids on Scedosporium species. Direct interactions between fungal and bacterial strains were tested using the disk inhibition method. Indirect interactions via volatile compounds were investigated by the plate-in-plate method, while the effect of bacterial media-soluble molecules was tested using a modified cellophane assay and also in liquid culture media conditioned by P. aeruginosa. To test the effect of bacterial signal molecules, antibacterial agents and corticosteroids on the fungal growth, the broth microdilution method was used. We also investigated the germination ability of Scedosporium conidia in the presence of pyocyanin and diffusible signal factor by microscopy. According to our results, P. aeruginosa either inhibited or enhanced the growth of scedosporia depending on the culture conditions and the mode of interactions. When the two pathogens were cultured physically separately from each other in the plate-in-plate tests, the presence of the bacteria was able to stimulate the growth of several fungal isolates. While in direct physical contact, bacterial strains inhibited the fungal growth. This effect might be attributed to bacterial signal molecules, which also proved to inhibit the germination and growth of scedosporia. In addition, antibacterial agents showed growth-promoting, while corticosteroids exhibited growth inhibitory effect on several Scedosporium isolates. These data raise the possibility that a P. aeruginosa infection or a previously administered antibacterial therapy might be able to increase the chance of a Scedosporium colonization in a CF lung.

PMID: 30894846 [PubMed]