Noncanonical Wnt planar cell polarity signaling in lung development and disease.

Biochem Soc Trans. 2020 Feb 25;:

Authors: Vladar EK, Königshoff M

Abstract
The planar cell polarity (PCP) signaling pathway is a potent developmental regulator of directional cell behaviors such as migration, asymmetric division and morphological polarization that are critical for shaping the body axis and the complex three-dimensional architecture of tissues and organs. PCP is considered a noncanonical Wnt pathway due to the involvement of Wnt ligands and Frizzled family receptors in the absence of the beta-catenin driven gene expression observed in the canonical Wnt cascade. At the heart of the PCP mechanism are protein complexes capable of generating molecular asymmetries within cells along a tissue-wide axis that are translated into polarized actin and microtubule cytoskeletal dynamics. PCP has emerged as an important regulator of developmental, homeostatic and disease processes in the respiratory system. It acts along other signaling pathways to create the elaborately branched structure of the lung by controlling the directional protrusive movements of cells during branching morphogenesis. PCP operates in the airway epithelium to establish and maintain the orientation of respiratory cilia along the airway axis for anatomically directed mucociliary clearance. It also regulates the establishment of the pulmonary vasculature. In adult tissues, PCP dysfunction has been linked to a variety of chronic lung diseases such as cystic fibrosis, chronic obstructive pulmonary disease, and idiopathic pulmonary arterial hypertension, stemming chiefly from the breakdown of proper tissue structure and function and aberrant cell migration during regenerative wound healing. A better understanding of these (impaired) PCP mechanisms is needed to fully harness the therapeutic opportunities of targeting PCP in chronic lung diseases.

PMID: 32096543 [PubMed - as supplied by publisher]

Real-life evaluation of clinical outcomes in patients undergoing treatment for non-tuberculous mycobacteria lung disease: A ten-year cohort study.

Respir Med. 2020 Feb 14;164:105899

Authors: Aliberti S, Sotgiu G, Castellotti P, Ferrarese M, Pancini L, Pasat A, Vanoni N, Spotti M, Mazzola E, Gramegna A, Saderi L, Perno CF, van Ingen J, Codecasa LR, Blasi F

Abstract
Outcome recognition is a crucial step in the management of non-tuberculous mycobacteria lung disease (NTM-LD). In order to explore NTM-LD outcomes in a real-life setting, an observational, retrospective study enrolling consecutive adults who received treatment for NTM-LD in Milan, Italy, from 2007 to 2017 was conducted. Among 170 patients (68.2% females; median age: 68 years), NTM-LD was mainly due to M. avium complex (MAC) (71.2%), M. kansasii (9.4%) and M. xenopi (7.1%). Along a median follow-up of 31 months, adverse events occurred in 37.6% of the patients. Treatment outcomes of the entire study population included an unsuccessful outcome in 35.3% of the patients, including treatment halted in 13.5%, recurrence in 11.2%, re-infection in 5.3%, treatment failure in 4.1% and relapse in 1.2%. The main reason for treatment halted was drug intolerance. No differences were detected between patients with MAC-LD vs. those with other NTM-LD in terms of unsuccessful outcome in general (35.5% vs. 34.7%). A significantly higher prevalence of patients who underwent treatment halted was found in patients with NTM-LD other than MAC in comparison to patients with MAC-LD (22.4% vs. 9.9%, p = 0.030). One third of adults undergoing treatment for a NTM-LD experiences an unsuccessful outcome with adverse events and treatment discontinuation being major challenges in patients' management.

PMID: 32094101 [PubMed - as supplied by publisher]

Complete versus Limited Endoscopic Sinus Surgery for Chronic Rhinosinusitis in Adults with Cystic Fibrosis.

Otolaryngol Head Neck Surg. 2020 Feb 25;:194599820904956

Authors: Lee DJ, Yao CMKL, Sykes J, Rizvi L, Tullis E, Lee JM

Abstract
OBJECTIVE: To examine the effects of the extent of endoscopic sinus surgery (ESS) on pulmonary health, including the pulmonary exacerbations and lung function in patients with cystic fibrosis (CF).
STUDY DESIGN: Retrospective cohort study.
SETTING: Tertiary health care center.
SUBJECTS AND METHODS: A retrospective review of patients with CF who underwent ESS at St. Michael's Hospital between 1999 and 2016 was performed. Two groups of patients were identified based on the surgical extent: (1) complete (maxillary antrostomy, complete ethmoidectomy, sphenoidotomy, and frontal sinusotomy) and (2) limited (any ESS that involved less than complete). Primary outcomes included the number of pulmonary exacerbations (the use of oral or intravenous [IV] antibiotics), number of hospital admissions and hospital days during a 2-year pre- and postoperative period, and pulmonary function outcomes during a 1-year pre- and postoperative period.
RESULTS: There were 70 procedures (30 complete and 40 limited) among 57 patients. Baseline characteristics were similar between the groups. Complete ESS group had a significant reduction in the oral antibiotic use compared to the limited ESS group (median, -1.0 [interquartile range (IQR), -2 to 0] in complete vs 0 [IQR, -1 to 1] in limited, P = .028). There was no difference in the use of IV antibiotics, number and duration of admissions, or rate of lung function change between the 2 groups.
CONCLUSION: Complete ESS may reduce mild forms of pulmonary exacerbations as shown in the decreased use of oral antibiotics. Overall, ESS does not significantly modify pulmonary outcomes in patients with CF.

PMID: 32093566 [PubMed - as supplied by publisher]

Anti-Infectives Restore ORKAMBI® Rescue of F508del-CFTR Function in Human Bronchial Epithelial Cells Infected with Clinical Strains of P. aeruginosa.

Biomolecules. 2020 Feb 19;10(2):

Authors: Laselva O, Stone TA, Bear CE, Deber CM

Abstract
Chronic infection and inflammation are the primary causes of declining lung function in Cystic Fibrosis (CF) patients. ORKAMBI® (Lumacaftor-Ivacaftor) is an approved combination therapy for Cystic Fibrosis (CF) patients bearing the most common mutation, F508del, in the cystic fibrosis conductance regulator (CFTR) protein. It has been previously shown that ORKAMBI®-mediated rescue of CFTR is reduced by a pre-existing Pseudomonas aeruginosa infection. Here, we show that the infection of F508del-CFTR human bronchial epithelial (HBE) cells with lab strain and four different clinical strains of P. aeruginosa, isolated from the lung sputum of CF patients, decreases CFTR function in a strain-specific manner by 48 to 88%. The treatment of infected cells with antibiotic tobramycin or cationic antimicrobial peptide 6K-F17 was found to decrease clinical strain bacterial growth on HBE cells and restore ORKAMBI®-mediated rescue of F508del-CFTR function. Further, 6K-F17 was found to downregulate the expression of pro-inflammatory cytokines, interleukin (IL)-8, IL-6, and tumor necrosis factor-α in infected HBE cells. The results provide strong evidence for a combination therapy approach involving CFTR modulators and anti-infectives (i.e., tobramycin and/or 6K-F17) to improve their overall efficacy in CF patients.

PMID: 32092967 [PubMed - in process]

Adult outcomes of childhood bronchiectasis.

Int J Circumpolar Health. 2020 Dec;79(1):1731059

Authors: Sibanda D, Singleton R, Clark J, Desnoyers C, Hodges E, Day G, Redding G

Abstract
Recent literature has highlighted the importance of transition from paediatric to adult care for children with chronic conditions. Non-cystic fibrosis bronchiectasis is an important cause of respiratory morbidity in low-income countries and in indigenous children from affluent countries; however, there is little information about adult outcomes of childhood bronchiectasis. We reviewed the clinical course of 31 Alaska Native adults 20-40 years of age from Alaska's Yukon Kuskokwim Delta with childhood bronchiectasis. In patients with chronic suppurative lung disease, a diagnosis of bronchiectasis was made at a median age of 4.5 years by computerised tomography (68%), bronchogram (26%), and radiographs (6%). The patients had a median of 75 lifetime respiratory ambulatory visits and 4.5 hospitalisations. As children, 6 (19%) experienced developmental delay; as adults 9 (29%) experienced mental illness or handicap. Four (13%) patients were deceased, four (13%) had severe pulmonary impairment in adulthood, 17 (54%) had persistent or intermittent respiratory symptoms, and seven (23%) were asymptomatic. In adulthood, only five were seen by adult pulmonologists and most had no documentation of a bronchiectasis diagnosis. Lack of provider continuity, remote location and co-morbidities can contribute to increased adult morbidity. Improving the transition to adult care starting in adolescence and educating adult providers may improve care of adults with childhood bronchiectasis.

PMID: 32090714 [PubMed - in process]

First case of cystic fibrosis in Greenland - diagnosed by neonatal screening.

J Cyst Fibros. 2020 Feb 20;:

Authors: M S, A K, M D

PMID: 32089517 [PubMed - as supplied by publisher]

CF: There's an app for that!

J Cyst Fibros. 2020 Feb 20;:

Authors: Nasr SZ, Lechtzin N

PMID: 32089516 [PubMed - as supplied by publisher]

New insights to guide patient care: the bidirectional relationship between male infertility and male health.

Fertil Steril. 2020 Feb 20;:

Authors: Kasman AM, Del Giudice F, Eisenberg ML

Abstract
Male reproduction is a complex process, and numerous medical conditions have the potential to alter spermatogenesis. In addition, male factor infertility may be a biomarker for future health. In the present review, we discuss the current literature regarding the association between systemic diseases and fertility, which may impact clinical outcomes or semen parameters. A number of conditions that have systemic consequences were identified, including genetic (e.g., cystic fibrosis, DNA mismatch repair alterations), obesity, psychological stress, exogenous testosterone, and a variety of common medications. As such, the infertility evaluation may offer an opportunity for health counseling beyond the discussion of reproductive goals. Moreover, male infertility has been suggested as a marker of future health, given that poor semen parameters and a diagnosis of male infertility are associated with an increased risk of hypogonadism, cardiometabolic disease, cancer, and even mortality. Therefore, male fertility requires multidisciplinary expertise for evaluation, treatment, and counseling.

PMID: 32089256 [PubMed - as supplied by publisher]

50 Years Ago in TheJournalofPediatrics: Sodium Concentration in Unstimulated Parotid Saliva and on Oral Mucosa in Normal Subjects and Patients with Cystic Fibrosis.

J Pediatr. 2020 Mar;218:77

Authors: Boat TF

PMID: 32089189 [PubMed - in process]

Clinical relevance of pulmonary non-tuberculous mycobacterial isolates in three reference centres in Belgium: a multicentre retrospective analysis.

BMC Infect Dis. 2019 Dec 17;19(1):1061

Authors: Vande Weygaerde Y, Cardinaels N, Bomans P, Chin T, Boelens J, André E, Van Braeckel E, Lorent N

Abstract
BACKGROUND/OBJECTIVES: Assessing the clinical relevance of non-tuberculous mycobacteria (NTM) isolated from respiratory samples can be challenging. The epidemiology and pathogenicity of NTM species vary geographically. We aimed to outline the clinical relevance and associated radiological patterns of NTM species isolated in Belgium.
METHODS: We performed a retrospective multicentre analysis of all patients identified from the laboratory database with > 1 respiratory sample growing NTM from January 2010 through December 2017. We collected clinical, radiological and microbiological data through medical record review and assessed clinical relevance according to ATS/IDSA criteria for NTM pulmonary disease (NTM-PD).
RESULTS: Of the 384 unique patients, 60% were male, 56% had a smoking history and 61% had pre-existing lung disease. Mycobacterium avium complex (MAC), M. gordonae and M. xenopi were the most frequently isolated species: 53, 15 and 8% respectively. 43% of patients met ATS/IDSA criteria, of whom 28% presented with fibrocavitary disease. Weight loss, fever, nodular bronchiectatic and fibrocavitary lesions on chest CT, and a positive acid-fast bacilli (AFB) stain were significantly associated with NTM-PD. The species with the highest pathogenic potential were M. abscessus (11/12), M. malmoense (6/7) and M. intracellulare (41/64).
CONCLUSION: In our study, MAC was the most commonly isolated NTM species, but M. abscessus and M. malmoense showed the highest probability of being clinically relevant. Clinical relevance varied not only by species but also by radiological findings on chest CT and AFB staining. Clinicians should consider these elements in their treatment decision making. Prospective data including clinical outcome are needed to provide more robust evidence.

PMID: 31847834 [PubMed - indexed for MEDLINE]

Peptide Nucleic Acids for MicroRNA Targeting.

Methods Mol Biol. 2020;2105:199-215

Authors: Gambari R, Gasparello J, Fabbri E, Borgatti M, Tamanini A, Finotti A

Abstract
The involvement of microRNAs in human pathologies is firmly established. Accordingly, the pharmacological modulation of microRNA activity appears to be a very interesting approach in the development of new types of drugs (miRNA therapeutics). One important research area is the possible development of miRNA therapeutics in the field of rare diseases. In this respect, appealing molecules are based on peptide nucleic acids (PNAs), displaying, in their first description, a pseudo-peptide backbone composed of N-(2-aminoethyl)glycine units, and found to be excellent candidates for antisense and antigene therapies. The aim of the present article is to describe methods for determining the activity of PNAs designed to target microRNAs involved in cystic fibrosis, using as model system miR-145-5p and its target cystic fibrosis transmembrane conductance regulator (CFTR) mRNA. The methods employed to study the effects of PNAs targeting miR-145-5p are presented here by discussing data obtained using as cellular model system the human lung epithelial Calu-3 cell line.

PMID: 32088872 [PubMed - as supplied by publisher]

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2020/02/23

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17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2020/02/22

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Targeting different binding sites in the CFTR structures allows to synergistically potentiate channel activity.

Eur J Med Chem. 2020 Feb 09;190:112116

Authors: Froux L, Elbahnsi A, Boucherle B, Billet A, Baatallah N, Hoffmann B, Alliot J, Zelli R, Zeinyeh W, Haudecoeur R, Chevalier B, Fortuné A, Mirval S, Simard C, Lehn P, Mornon JP, Hinzpeter A, Becq F, Callebaut I, Décout JL

Abstract
Recent evidence shows that combination of correctors and potentiators, such as the drug ivacaftor (VX-770), can significantly restore the functional expression of mutated Cystic Fibrosis Transmembrane conductance Regulator (CFTR), an anion channel which is mutated in cystic fibrosis (CF). The success of these combinatorial therapies highlights the necessity of identifying a broad panel of specific binding mode modulators, occupying several distinct binding sites at structural level. Here, we identified two small molecules, SBC040 and SBC219, which are two efficient cAMP-independent potentiators, acting at low concentration of forskolin with EC50 close to 1 μM and in a synergic way with the drug VX-770 on several CFTR mutants of classes II and III. Molecular dynamics simulations suggested potential SBC binding sites at the vicinity of ATP-binding sites, distinct from those currently proposed for VX-770, outlining SBC molecules as members of a new family of potentiators.

PMID: 32078860 [PubMed - as supplied by publisher]

Pulmonary artery enlargement is associated with pulmonary hypertension and decreased survival in severe cystic fibrosis: A cohort study.

PLoS One. 2020;15(2):e0229173

Authors: Zouk AN, Gulati S, Xing D, Wille KM, Rowe SM, Wells JM

Abstract
BACKGROUND: Pulmonary artery (PA) enlargement, defined as pulmonary artery to ascending aorta diameter ratio (PA:A)>1 on computed tomography (CT), is a marker of pulmonary vascular disease in chronic lung diseases. PA enlargement is prevalent in cystic fibrosis (CF), but its relationship to hemodynamics and prognostic utility in severe CF are unknown. We hypothesized that the PA:A would have utility in identifying pulmonary hypertension (PH) in severe CF and that PA enlargement would be associated with reduced transplant-free survival.
METHODS: We conducted a retrospective study of adults with CF undergoing lung transplant evaluation at a single center between 2000 and 2015. CT, right heart catheterization (RHC), and clinical data were collected. The PA:A was measured from a single CT slice. We measured associations between PA:A and invasive hemodynamic parameters including PH defined as a mPAP ≥25mmHg using adjusted linear and logistic regression models. Kaplan-Meier and adjusted Cox regression models were used to measure associations between PA:A>1, RHC-defined PH, and transplant-free survival in severe CF.
RESULTS: We analyzed 78 adults with CF that had CT scans available for review, including 44 that also had RHC. RHC-defined PH defined as a mPAP ≥25mmHg was present in 36% of patients with CF undergoing transplant evaluation. The PA:A correlated with mPAP (r = 0.73; 95% CI 3.87-7.80; p<0.001) and PVR (r = 0.42, p = 0.005) and the PA:A>1 was an independent predictor of PH (aOR 4.50; 95% CI 1.05-19.2; p = 0.042). PA:A>1 was independently associated with increased hazards for death or transplant (aHR 2.69; 95% CI 1.41-5.14; P = 0.003). The presence of mPAP ≥25mmHg was independently associated with decreased survival in this cohort.
CONCLUSIONS: PA enlargement is associated with pulmonary hemodynamics and PH in severe CF. PA enlargement is an independent prognostic indicator of PH and decreased survival in this population.

PMID: 32078644 [PubMed - as supplied by publisher]

European Position Paper on Rhinosinusitis and Nasal Polyps 2020.

Rhinology. 2020 Feb 20;58(Suppl S29):1-464

Authors: Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, Toppila-Salmi S, Bernal-Sprekelsen M, Mullol J, Alobid I, Terezinha Anselmo-Lima W, Bachert C, Baroody F, von Buchwald C, Cervin A, Cohen N, Constantinidis J, De Gabory L, Desrosiers M, Diamant Z, Douglas RG, Gevaert PH, Hafner A, Harvey RJ, Joos GF, Kalogjera L, Knill A, Kocks JH, Landis BN, Limpens J, Lebeer S, Lourenco O, Matricardi PM, Meco C, O Mahony L, Philpott CM, Ryan D, Schlosser R, Senior B, Smith TL, Teeling T, Tomazic PV, Wang DY, Wang D, Zhang L, Agius AM, Ahlstrom-Emanuelsson C, Alabri R, Albu S, Alhabash S, Aleksic A, Aloulah M, Al-Qudah M, Alsaleh S, Baban MA, Baudoin T, Balvers T, Battaglia T, Bedoya JD, Beule A, Bofares KM, Braverman I, Brozek-Madry E, Richard B, Callejas C, Carrie S, Caulley L, Chussi D, de Corso E, Coste A, Devyani L, El Hadi U, Elfarouk A, Eloy PH, Farrokhi S, Felisati G, Ferrari MD, Fishchuk R, Grayson W, Goncalves PM, Grdinic B, Grgic V, Hamizan AW, Heinichen JV, Husain S, Ping TI, Ivaska J, Jakimovska F, Jovancevic L, Kakande E, Kamel R, Karpischenko S, Kariyawasam HH, Kjeldsen A, Klimek L, Kim SW, Letort JJ, Lopatin A, Mahdjoubi A, Netkovski J, Nyenbue Tshipukane D, Obando-Valverde A, Okano M, Onerci M, Ong YK, Orlandi R, Ouennoughy K, Ozkan M, Peric A, Plzak J, Prokopakis E, Prepageran N, Psaltis A, Pugin B, Raftopulos M, Rombaux P, Sahtout S, Sarafoleanu CC, Searyoh K, Rhee CS, Shi J, Shkoukani M, Shukuryan AK, Sicak M, Smyth D, Snidvongs K, Soklic Kosak T, Stjarne P

Abstract
The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

PMID: 32077450 [PubMed - in process]

Postinfectious Bronchiolitis Obliterans in Children: Diagnostic Workup and Therapeutic Options: A Workshop Report.

Can Respir J. 2020;2020:5852827

Authors: Jerkic SP, Brinkmann F, Calder A, Casey A, Dishop M, Griese M, Kurland G, Niemitz M, Nyilas S, Schramm D, Schubert R, Tamm M, Zielen S, Rosewich M

Abstract
Bronchiolitis obliterans (BO) is a rare, chronic form of obstructive lung disease, often initiated with injury of the bronchiolar epithelium followed by an inflammatory response and progressive fibrosis of small airways resulting in nonuniform luminal obliteration or narrowing. The term BO comprises a group of diseases with different underlying etiologies, courses, and characteristics. Among the better recognized inciting stimuli leading to BO are airway pathogens such as adenovirus and mycoplasma, which, in a small percentage of infected children, will result in progressive fixed airflow obstruction, an entity referred to as postinfectious bronchiolitis obliterans (PIBO). The present knowledge on BO in general is reasonably well developed, in part because of the relatively high incidence in patients who have undergone lung transplantation or bone marrow transplant recipients who have had graft-versus-host disease in the posttransplant period. The cellular and molecular pathways involved in PIBO, while assumed to be similar, have not been adequately elucidated. Since 2016, an international consortium of experts with an interest in PIBO assembles on a regular basis in Geisenheim, Germany, to discuss key areas in PIBO which include diagnostic workup, treatment strategies, and research fields.

PMID: 32076469 [PubMed - in process]

Effect of Inspiratory Maneuvers on Lung Deposition of Tobramycin Inhalation Powder: A Modeling Study.

J Aerosol Med Pulm Drug Deliv. 2020 Feb 19;:

Authors: Meerburg JJ, Andrinopoulou ER, Bos AC, Shin H, van Straten M, Hamed K, Mastoridis P, Tiddens HAWM

Abstract
Background: Tobramycin inhalation powder (TIP) and tobramycin inhalation solution (TIS) are considered equally effective for the treatment of chronic pulmonary Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients. The impact of TIP inhalation maneuvers on distribution of tobramycin is unknown. We hypothesized that (1) fast TIP inhalations result in greater extrathoracic and reduced small airway concentrations compared with slow or uninstructed TIP inhalations; (2) slow TIP inhalations result in greater small airway concentrations than TIS inhalations. The aim of the study was to assess TIP and TIS deposition with computational fluid dynamics (CFD). Methods: Uninstructed, instructed fast, and instructed slow TIP inhalations of CF patients on maintenance TIP therapy, and inhalations during nebulization of saline with PARI LC Plus® were recorded at home. Drug deposition was determined using TIP and TIS aerosol characteristics together with CFD simulations based on airway geometries from chest computed tomography scans. The drug concentration was assessed in extrathoracic, central, large, and small airways. Results: Twelve patients aged 12-45 years were included, and 144 CFD simulations were performed. In all individual analyses, the tobramycin concentrations were well above the threshold for effective dose of 10 times minimal inhibitory concentration throughout the bronchial tree. Extrathoracic concentrations were comparable between fast and uninstructed TIP inhalations, while slow inhalations resulted in reduced extrathoracic concentrations compared with uninstructed TIP inhalations (p = 0.024). Small airway concentrations were comparable between fast and uninstructed TIP inhalations, while slow TIP inhalations resulted in greater small airway concentrations than uninstructed TIP inhalations (p < 0.001). Small airway concentrations of TIS were comparable with those of slow TIP inhalations (p = 0.065), but greater than those of fast and uninstructed TIP inhalations (p < 0.001). Conclusion: All TIS and TIP inhalation maneuvers resulted in high enough concentrations, however, inhaling TIS or inhaling TIP slowly results in the greatest small airway deposition.

PMID: 32073919 [PubMed - as supplied by publisher]

Derivation of induced pluripotent stem cells from ferret somatic cells.

Am J Physiol Lung Cell Mol Physiol. 2020 Feb 19;:

Authors: Gao J, Petraki S, Sun X, Brooks LA, Lynch TJ, Hsieh CL, Elteriefi R, Lorenzana Z, Punj V, Engelhardt JF, Parekh KR, Ryan AL

Abstract
Ferrets are an attractive mammalian model for several diseases especially those affecting the lungs, liver and kidneys. Many chronic human diseases have been difficult to model in rodents due to differences in size and cellular anatomy. This is particularly the case for the lung where ferrets provide an attractive mammalian model of both acute and chronic lung diseases such as influenza, cystic fibrosis, A1A emphysema and obliterative bronchiolitis, closely recapitulating disease pathogenesis as it occurs in humans. As such, ferrets have the potential to be a valuable pre-clinical model for the evaluation of cell-based therapies for lung regeneration and, likely, for other tissues. Induced pluripotent stem cells (iPSCs) provide a great option for provision of enough autologous cells to make patient-specific cell therapies a reality. Unfortunately, they have not been successfully created from ferrets. In this study, we demonstrate the generation of ferret iPSCs that reflect the primed pluripotent state of human iPSCs. Ferret fetal fibroblasts were reprogrammed and acquired core features of pluripotency, having the capacity for self-renewal, multi-lineage differentiation and a high-level expression of the core pluripotency genes and pathways at both the transcriptional and protein level. In conclusion, we have generated ferret pluripotent stem cells that provide an opportunity for advancing our capacity to evaluate autologous cell engraftment in ferrets.

PMID: 32073882 [PubMed - as supplied by publisher]

Effectiveness of chest physiotherapy and pulmonary rehabilitation in patients with non-cystic fibrosis bronchiectasis: a narrative review.

Monaldi Arch Chest Dis. 2020 Feb 12;90(1):

Authors: Annoni S, Bellofiore A, Repossini E, Lazzeri M, Nicolini A, Tarsia P

Abstract
Respiratory physiotherapy and rehabilitation are important therapeutic options in non-cystic fibrosis bronchiectasis (NCFB). The aims of this review of clinical trials were to evaluate the safety and the effects on physiologic and clinical outcomes of airway clearance techniques (ACTs) and rehabilitation in NCFB patients, in comparison to usual care. The search was performed on March 2018 by using PubMed and PeDro databases. 33 studies were selected. The use of ACTs for NCFB were effective in increasing sputum volume although no benefit in quality of life (QoL) or pulmonary exacerbations were observed. There were no differences in effectiveness between the several techniques used. Humidification and saline inhalation were able to aid airway clearance. Hypertonic solution (HS) was more effective than isotonic solutions (IS) in improving expectoration and sputum viscosity. Pulmonary rehabilitation (PR) was found to be associated with short term benefits in exercise capacity, dyspnea and fatigue. Exercise training seems to improve quality of life and lower exacerbation rate, but long-term data are not available. Further studies are necessary to identify the most feasible long-term outcomes such as QoL and exacerbation rate.

PMID: 32072797 [PubMed - in process]