Impaired glucose tolerance, body mass index and respiratory function in patients with cystic fibrosis: A systematic review.

Clin Respir J. 2019 Mar 28;:

Authors: Iwanicki C, Logomarsino JV

Abstract
OBJECTIVES: This systematic review aims to evaluate body mass index (BMI) and forced expiratory volume in one second (FEV1 ) in patients with cystic fibrosis (CF) diagnosed with impaired glucose tolerance (IGT) compared to those with normal glucose tolerance (NGT). The significance of this topic stems from concern that individuals with CF and IGT may have an overall worse clinical status as indicated by BMI and FEV1 .
DATA SOURCE: An exhaustive literature search was completed between July 2017 and September 2017 using PubMed, CINAHL, Web of Science, Dissertations & Theses, PsycINFO, and Open Grey. Studies were limited to human subjects with CF. There were no restrictions on publication date, study design, or language.
STUDY SELECTION: Included studies examined BMI and FEV1 as outcome measures in individuals with CF and IGT compared to those with NGT. After screening for inclusion criteria, 12 observational studies met the specified conditions.
RESULTS: Two studies showed a significantly worse BMI and FEV1 in subjects with CF and IGT compared to those with NGT. The remaining 10 studies found no significant associations with BMI and FEV1 in subjects with CF and IGT compared to NGT.
CONCLUSION: Although this review does not prove cause and effect, BMI and FEV1 are important outcome measures in patients with CF. Considering the inconclusive findings, practitioners should individualize care for this patient population. Additional research should focus on clinical status and interventions/treatment for individuals with CF and IGT. This article is protected by copyright. All rights reserved.

PMID: 30919537 [PubMed - as supplied by publisher]

Transmission of bacteria in bronchiectasis and chronic obstructive pulmonary disease: Low burden of cough aerosols.

Respirology. 2019 Mar 27;:

Authors: Stockwell RE, Chin M, Johnson GR, Wood ME, Sherrard LJ, Ballard E, O'Rourke P, Ramsay KA, Kidd TJ, Jabbour N, Thomson RM, Knibbs LD, Morawska L, Bell SC

Abstract
BACKGROUND AND OBJECTIVE: Aerosol transmission of Pseudomonas aeruginosa has been suggested as a possible mode of respiratory infection spread in patients with cystic fibrosis (CF); however, whether this occurs in other suppurative lung diseases is unknown. Therefore, we aimed to determine if (i) patients with bronchiectasis (unrelated to CF) or chronic obstructive pulmonary disease (COPD) can aerosolize P. aeruginosa during coughing and (ii) if genetically indistinguishable (shared) P. aeruginosa strains are present in these disease cohorts.
METHODS: People with bronchiectasis or COPD and P. aeruginosa respiratory infection were recruited for two studies. Aerosol study: Participants (n = 20) underwent cough testing using validated cough rigs to determine the survival of P. aeruginosa aerosols in the air over distance and duration. Genotyping study: P. aeruginosa sputum isolates (n = 95) were genotyped using the iPLEX20SNP platform, with a subset subjected to the enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) assay to ascertain their genetic relatedness.
RESULTS: Aerosol study: Overall, 7 of 20 (35%) participants released P. aeruginosa cough aerosols during at least one of the cough aerosol tests. These cough aerosols remained viable for 4 m from the source and for 15 min after coughing. The mean total aerosol count of P. aeruginosa at 2 m was two colony-forming units. Typing study: No shared P. aeruginosa strains were identified.
CONCLUSION: Low viable count of P. aeruginosa cough aerosols and a lack of shared P. aeruginosa strains observed suggest that aerosol transmission of P. aeruginosa is an unlikely mode of respiratory infection spread in patients with bronchiectasis and COPD.

PMID: 30919511 [PubMed - as supplied by publisher]

Antibiotic susceptibility and production of endotoxin by Ochrobactrum anthropi isolated from environment and from patients with cystic fibrosis.

Folia Microbiol (Praha). 2019 Mar 27;:

Authors: Chmelař D, Holý O, Kasáková I, Hájek M, Lazarová A, Gonzalez-Rey C, Lasák J, Raclavský V, Čižnár I

Abstract
The aim of this work was to compare production of endotoxin and to determine susceptibility to antibiotics in two groups of specimens-wild-type strains Ochrobactrum anthropi isolated from the environment and the strains isolated from patients with cystic fibrosis. The determination of the endotoxin produced by the test strains was carried on by using a limulus amebocyte lysate test (LAL test). Determination of ATB sensitivity was accomplished by means of a broth dilution method in a microtiter plate (MIC). No significant difference was found between the group of ochrobacters isolated from the environment and the group of ochrobacters isolated from cystic fibrosis patients. Antibiotic sensitivity testing has indicated that the resistance to tigecycline, trimethoprim/sulfamethoxazole, and gentamicin was slightly higher in strains isolated from cystic fibrosis patients in comparison with strains isolated from the environment. In general, most of the test strains were sensitive to most of the antibiotics tested. Significant resistance has been demonstrated for cefotaxime. Resistance was also found for gentamicin in strains number 4 and 7. The MIC was equal to the breakpoint for this antibiotic (8000 mg/L).

PMID: 30919306 [PubMed - as supplied by publisher]

In utero and postnatal VX-770 administration rescues multiorgan disease in a ferret model of cystic fibrosis.

Sci Transl Med. 2019 Mar 27;11(485):

Authors: Sun X, Yi Y, Yan Z, Rosen BH, Liang B, Winter MC, Evans TIA, Rotti PG, Yang Y, Gray JS, Park SY, Zhou W, Zhang Y, Moll SR, Woody L, Tran DM, Jiang L, Vonk AM, Beekman JM, Negulescu P, Van Goor F, Fiorino DF, Gibson-Corley KN, Engelhardt JF

Abstract
Cystic fibrosis (CF) is a multiorgan disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). In patients with CF, abnormalities initiate in several organs before birth. However, the long-term impact of these in utero pathologies on disease pathophysiology is unclear. To address this issue, we generated ferrets harboring a VX-770 (ivacaftor)-responsive CFTR G551D mutation. In utero VX-770 administration provided partial protection from developmental pathologies in the pancreas, intestine, and male reproductive tract. Homozygous CFTR G551D/G551D animals showed the greatest VX-770-mediated protection from these pathologies. Sustained postnatal VX-770 administration led to improved pancreatic exocrine function, glucose tolerance, growth and survival, and to reduced mucus accumulation and bacterial infections in the lung. VX-770 withdrawal at any age reestablished disease, with the most rapid onset of morbidity occurring when withdrawal was initiated during the first 2 weeks after birth. The results suggest that CFTR is important for establishing organ function early in life. Moreover, this ferret model provides proof of concept for in utero pharmacologic correction of genetic disease and offers opportunities for understanding CF pathogenesis and improving treatment.

PMID: 30918114 [PubMed - in process]

Prevention of cystic fibrosis: The beginning of the end?

Sci Transl Med. 2019 Mar 27;11(485):

Authors: Ferkol TW

Abstract
Prenatal and postnatal treatment with a CFTR modifier attenuates pathological changes in a ferret model of cystic fibrosis (Sun et al., this issue).

PMID: 30918110 [PubMed - in process]

Safety and efficacy of the human neutrophil elastase inhibitor BAY 85-8501 for the treatment of non-cystic fibrosis bronchiectasis: a randomized controlled trial.

Pulm Pharmacol Ther. 2019 Mar 24;:

Authors: Watz H, Nagelschmitz J, Kirsten A, Pedersen F, van der Mey D, Schwers S, Bandel TJ, Rabe KF

Abstract
BACKGROUND: There are only limited treatment options for patients with non-cystic fibrosis bronchiectasis (non-CF BE). Human neutrophil elastase (HNE) is a mediator of tissue destruction in non-CF BE. BAY 85-8501, a selective and reversible HNE inhibitor, could represent a new treatment option for this disease.
METHODS: This was a phase 2a, randomized, placebo-controlled, double-blind, parallel-group study. The primary objective was to assess the safety and tolerability of 1 mg BAY 85-8501 once daily (OD) for 28 days compared with placebo in patients with non-CF BE. Secondary objectives were to investigate the effects of 4 weeks of treatment with BAY 85-8501 on health-related quality of life, pulmonary function, and inflammatory and tissue damage biomarkers in sputum, blood and/or urine, and to evaluate the pharmacokinetics of BAY 85-8501.
RESULTS: Overall, 94 patients (mean age, 66 years; 53% male) were randomized (n = 47 per group), and 82 completed the study (BAY 85-8501, n = 37; placebo, n = 45). Treatment-emergent adverse events (TEAEs) occurred in 31 patients (66%) taking BAY 85-8501 and in 36 patients (77%) taking placebo, and were mostly mild or moderate. The serious TEAEs (BAY 85-8501, n = 3; placebo, n = 1) were not considered to be study-drug related. There were no changes in pulmonary function parameters from baseline to end of treatment, and health-related quality of life did not improve in any group. HNE activity in blood after zymosan challenge decreased significantly with BAY 85-8501 treatment (P = 0.0250 versus placebo). There were no significant differences in other biomarkers between treatment groups, with the exception of a small increase in interleukin-8 levels in sputum in the BAY 85-8501 group. Trough plasma concentrations of BAY 85-8501 plateaued after 2 weeks.
CONCLUSIONS: 1 mg BAY 85-8501 OD had a favourable safety and tolerability profile when administered for 28 days to patients with non-CF BE. Further studies with a longer treatment duration are needed to evaluate the potential clinical efficacy in this study population.

PMID: 30917927 [PubMed - as supplied by publisher]

Evidence-Based Medicine: Can We Trust the Evidence Informing Clinical Practice?

J Allied Health. 2018;47(4):296-299

Authors: Gambazza S

Abstract
An attempt to distinguish science from folklore in medical practice was made in 1991, when a new paradigm called evidence-based medicine (EBM) officially appeared. Although this approach was meant to avoid clinical entropy, it might constitute a barrier for contemporary health enhancement, generating results that could be selectively chosen or obtained through misapplication of frequent statistics. At worst, only few health professions can take advantage from this supposed demarcation criterion, lacking the infrastructure and institutional support to carry on research and thus offering a risky disservice to patients. The potential of technology applied to health should be investigated further, and exploring and learning from other approaches than EBM should be encouraged, taking into account the way in which we assess reality and the biological substrate of our learning processes.

PMID: 30508842 [PubMed - indexed for MEDLINE]

CFTR gating: Invisible transitions made visible.

J Gen Physiol. 2017 04 03;149(4):413-416

Authors: Csanády L

PMID: 28264886 [PubMed - indexed for MEDLINE]

Update in Cystic Fibrosis.

Am J Respir Crit Care Med. 2019 Mar 27;:

Authors: Ramsey BW, Downey GP, Goss CH

PMID: 30917288 [PubMed - as supplied by publisher]

CFAP300: Mutations in Slavic Primary Ciliary Dyskinesia Patients and a Role in Ciliary Dynein Arms Trafficking.

Am J Respir Cell Mol Biol. 2019 Mar 27;:

Authors: Zietkiewicz E, Bukowy-Bieryllo Z, Rabiasz A, Daca-Roszak P, Wojda A, Voelkel K, Rutkiewicz E, Pogorzelski A, Rasteiro M, Witt M

Abstract
Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous hereditary disease from a class of ciliopathies. In spite of the recent progress, the genetic basis of PCD in 1/3 of patients remains unknown. In search for new genes and/or mutations, the whole-exome sequencing was performed in 120 unrelated Polish PCD patients, in whom no genetic cause of PCD was earlier identified. Among a number of pathogenic variants in PCD genes, mutations in CFAP300 (alias C11orf70) were detected. Extended screening in the whole Polish PCD cohort revealed the relatively high frequency (3.6%) of otherwise rare c.[198_200del_insCC] variant, indicating that it should be included in population-specific genetic tests for PCD in Slavic population. Immunofluorescence analysis of the respiratory epithelial cells from patients with CFAP300 mutations revealed the absence or aberrant localization of outer and inner dynein arms markers, consistent with the transition electron microscope images indicating the lack of both dynein arms. Interestingly, the disparate localization of DNAH5 and DNALI1 proteins in CFAP300 patients suggested differential mechanisms for the trafficking of preassembled outer and inner dynein arms to the axoneme. The profile of CFAP300 expression during ciliogenesis in suspension culture was consistent with its role in cilia assembly. Gene silencing experiments, performed in a model organism, Schmidtea mediterranea flatworm, pointed to the conserved role of CFAP300 in the ciliary function.

PMID: 30916986 [PubMed - as supplied by publisher]

Evidence for a role of arginine vasotocin (AVT) receptors in the gill during salinity acclimation by a euryhaline teleost fish.

Am J Physiol Regul Integr Comp Physiol. 2019 Mar 27;:

Authors: Lema SC, Washburn EH, Crowley ME, Carvalho PG, Egelston JN, McCormick SD

Abstract
The nonapeptide arginine vasotocin (AVT) regulates osmotic balance in teleost fishes, but its mechanisms of action are not fully understood. Recently, it was discovered that nonapeptide receptors in teleost fishes are differentiated into two V1a-type, several V2-type, and two isotocin (IT) receptors, but it remains unclear which receptors mediate AVT's effects on gill osmoregulation. Here, we examined the role of nonapeptide receptors in the gill of the euryhaline Amargosa pupfish, Cyprinodon nevadensis amargosae, during osmotic acclimation. Transcripts for the teleost V1a-type receptor v1a2 were up-regulated over 4-fold in gill 24 h after transferring pupfish from 7.5 ppt to seawater (35 ppt) or hypersaline (55 ppt) conditions, and down-regulated after transfer to freshwater (0.3 ppt). Gill transcripts for the nonapeptide degradation enzyme leucyl-cystinyl aminopeptidase (LNPEP) also increased in fish acclimating to 35 ppt. To test whether AVT's effects on the gill might be mediated by a V1a-type receptor, we administered AVT or a V1-type receptor antagonist (Manning compound) intraperitoneally to pupfish prior to transfer to 0.4 ppt or 35 ppt. Pupfish transferred to 35 ppt exhibited elevated gill mRNA abundance for cystic fibrosis transmembrane conductance regulator ( cftr), but that up-regulation diminished under V1-receptor inhibition. AVT inhibited the increase in gill Na+/Cl- cotransporter 2 ( ncc2) transcript abundance that occurs following transfer to hypo-osmotic environments, while V1-type receptor antagonism increased ncc2 mRNAs even without a change in salinity. These findings indicate AVT acts via a V1-type receptor to regulate gill Cl- transport by inhibiting Cl- uptake and facilitating Cl- secretion during seawater acclimation.

PMID: 30916577 [PubMed - as supplied by publisher]

Plasma membrane-localized TMEM16 proteins are indispensable for expression of CFTR.

J Mol Med (Berl). 2019 Mar 26;:

Authors: Benedetto R, Ousingsawat J, Cabrita I, Pinto M, Lérias JR, Wanitchakool P, Schreiber R, Kunzelmann K

Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is the secretory chloride channel in epithelial tissues that has a central role in cystic fibrosis (CF) lung and gastrointestinal disease. A recent publication demonstrates a close association between CFTR and TMEM16A, the calcium-activated chloride channel. Thus, no CFTR chloride currents could be detected in airways and large intestine from mice lacking epithelial expression of TMEM16A. Here, we demonstrate that another plasma membrane-localized TMEM16 paralogue, TMEM16F, can compensate for the lack of TMEM16A. Using TMEM16 knockout mice, human lymphocytes, and a number of human cell lines with endogenous protein expression or heterologous expression, we demonstrate that CFTR can only function in the presence of either TMEM16A or TMEM16F. Double knockout of intestinal epithelial TMEM16A/F expression did not produce offsprings, suggesting a lethal phenotype in utero. Plasma membrane-localized TMEM16A or TMEM16F is required for exocytosis and expression of CFTR in the plasma membrane. TMEM16A/F proteins may therefore have an impact on disease severity in CF. KEY MESSAGES: • Cystic fibrosis is caused by the defective Cl- channel cystic fibrosis transmembrane conductance regulator (CFTR). • A close relationship exists between CFTR and the calcium-activated chloride channels TMEM16A/TMEM16F. • In conditional airway and intestinal knockout mice, lymphocytes from Scott disease patients and in overexpressing cells, CFTR is not functional in the absence of TMEM16A and TMEM16F. • TMEM16A and TMEM16F support membrane exocytosis and are essential for plasma membrane insertion of CFTR.

PMID: 30915480 [PubMed - as supplied by publisher]

Activity and Impact on Resistance Development of Two Antivirulence Fluoropyrimidine Drugs in Pseudomonas aeruginosa.

Front Cell Infect Microbiol. 2019;9:49

Authors: Imperi F, Fiscarelli EV, Visaggio D, Leoni L, Visca P

Abstract
The rise in antibiotic resistance among bacterial pathogens has prompted the exploitation of alternative antibacterial strategies, such as antivirulence therapy. By inhibiting virulence traits, antivirulence drugs are expected to lessen pathogenicity without affecting bacterial growth, therefore avoiding the spread of resistance. However, some studies argued against this assumption, and the lack of antivirulence drugs in clinical use hampers the empirical assessment of this concept. Here we compared the mode of action and range of activity of two drugs which have been proposed for repurposing as quorum sensing and pyoverdine inhibitors in the human pathogen Pseudomonas aeruginosa: the anticancer drug 5-fluorouracil (5-FU) and the antimycotic drug 5-fluorocytosine (5-FC), respectively. The effect on bacterial growth, emergence and spread of resistance, and activity against clinical isolates were assessed. Our results confirm that 5-FU has growth inhibitory activity on reference strains and can rapidly select for spontaneous resistant mutants with loss-of-function mutations in the upp gene, responsible for uracil conversion into UMP. These mutants were also insensitive to the anti-pyoverdine effect of 5-FC. Conversely, 5-FC did not cause relevant growth inhibition, likely because of poor enzymatic conversion into 5-FU by cytosine deaminase. However, coculturing experiments showed that 5-FU resistant mutants can outcompete sensitive cells in mixed populations, in the presence of not only 5-FU but also 5-FC. Moreover, we observed that serial passages of wild-type cells in 5-FC-containing medium leads to the appearance and spread of 5-FC insensitive sub-populations of 5-FU resistant cells. The different effect on growth of 5-FU and 5-FC was overall conserved in a large collection of cystic fibrosis (CF) isolates, corresponding to different infection stages and antibiotic resistance profiles, although high variability was observed among strains. Notably, this analysis also revealed a significant number of pyoverdine-deficient isolates, whose proportion apparently increases over the course of the CF infection. This study demonstrates that the efficacy of an antivirulence drug with no apparent effect on growth can be significantly influenced by the emergence of insensitive mutants, and highlights the importance of the assessment of resistance-associated fitness cost and activity on clinical isolates for the development of "resistance-proof" antivirulence drugs.

PMID: 30915278 [PubMed - in process]

Longitudinal development of the airway microbiota in infants with cystic fibrosis.

Sci Rep. 2019 Mar 26;9(1):5143

Authors: Ahmed B, Cox MJ, Cuthbertson L, James P, Cookson WOC, Davies JC, Moffatt MF, Bush A

Abstract
The pathogenesis of airway infection in cystic fibrosis (CF) is poorly understood. We performed a longitudinal study coupling clinical information with frequent sampling of the microbiota to identify changes in the airway microbiota in infancy that could underpin deterioration and potentially be targeted therapeutically. Thirty infants with CF diagnosed on newborn screening (NBS) were followed for up to two years. Two hundred and forty one throat swabs were collected as a surrogate for lower airway microbiota (median 35 days between study visits) in the largest longitudinal study of the CF oropharyngeal microbiota. Quantitative PCR and Illumina sequencing of the 16S rRNA bacterial gene were performed. Data analyses were conducted in QIIME and Phyloseq in R. Streptococcus spp. and Haemophilus spp. were the most common genera (55% and 12.5% of reads respectively) and were inversely related. Only beta (between sample) diversity changed with age (Bray Curtis r2 = 0.15, P = 0.03). Staphylococcus and Pseudomonas were rarely detected. These results suggest that Streptococcus spp. and Haemophilus spp., may play an important role in early CF. Whether they are protective against infection with more typical CF micro-organisms, or pathogenic and thus meriting treatment needs to be determined.

PMID: 30914718 [PubMed - in process]

MARKEDLY DELAYED INSULIN SECRETION AND A HIGH RATE OF UNDETECTED OVERT DIABETES CHARACTERIZE GLUCOSE METABOLISM IN ADULT PATIENTS WITH CYSTIC FIBROSIS AFTER LUNG TRANSPLANTATION.

Endocr Pract. 2019 Mar;25(3):254-262

Authors: Winhofer Y, Wolf P, Fellinger P, Tura A, Hillebrand P, Staufer K, Trauner M, Jaksch P, Muraközy G, Kautzky-Willer A, Pacini G, Krebs M, Luger A, Kazemi-Shirazi L

Abstract
OBJECTIVE: Cystic fibrosis-related diabetes (CFRD) is associated with adverse clinical outcomes and should be screened for by an annual oral glucose tolerance test (OGTT). Since pathophysiologic studies have mainly been performed in a pediatric/adolescent, nontransplanted collective, we aimed to assess parameters of insulin secretion and sensitivity in adult cystic fibrosis (CF) patients after lung transplantation (LT).
METHODS: Twelve adult CF patients after LT without known diabetes (33.3 ± 11.5 years; body mass index [BMI] 21.5 ± 3.3 kg/m2) and 8 control subjects matched by age (36.0 ± 6.6 years; P>.05), BMI (22.3 ± 1.5 kg/m2; P>.05), and gender (CON group) underwent a 3-hour OGTT with glucose, insulin, and C-peptide measurements. Parameters of insulin secretion and sensitivity as well as lipid profiles were assessed.
RESULTS: In the CF group, 4 patients were diagnosed with overt diabetes (CFRD) compared to CF patients without diabetes (CF-noDM), of whom 6 had indeterminate glycemia with 1-h glucose values >200 mg/dL. The insulin peak after glucose load occurred after 30 minutes in CON, after 90 minutes in CF-noDM, and was missing in CFRD. Insulin sensitivity was comparable between the groups. Beta-cell glucose sensitivity was markedly reduced in CFRD (10.7 ± 5.8 pmol/min*m2*mM), higher in CF-noDM (39.9 ± 23.4 pmol/min*m2*mM), but still significantly lower compared to CON (108.3 ± 53.9 pmol/min*m2*mM; P = .0008). CFRD patients exhibited increased triglyceride levels and decreased high-density lipoprotein levels.
CONCLUSION: Adult CF patients after LT have profound disturbances in glucose metabolism, with a high rate of undetected diabetes and markedly delayed insulin secretion. Curbed beta-cell glucose sensitivity rather than insulin resistance explains postprandial hyperglycemia and is accompanied by abnormalities in lipid metabolism.
ABBREVIATIONS: AUC = area under the curve; BMI = body mass index; CF = cystic fibrosis; CFRD = cystic fibrosis-related diabetes; CFTR = cystic fibrosis transmembrane-conductance regulator; CF-TX = cystic fibrosis patients who underwent lung transplantation; CGM = continuous glucose monitoring; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; INDET = indeterminate glycemia; LDL = low-density lipoprotein; LT = lung transplantation; OGIS = oral glucose sensitivity index; OGTT = oral glucose tolerance test; QUICKI = quantitative insulin sensitivity check index.

PMID: 30913015 [PubMed - in process]

[Diagnostic possibilities of modern biochemical study of sputum from patients with cystic fibrosis (literature review).]

Klin Lab Diagn. 2019;64(1):24-28

Authors: Kozlov AV, Gusyakova OA, Ereshchenko AA, Khaliulin AV

Abstract
The review presents the pathobiochemical and molecular mechanisms of sputum formation in patients with cystic fibrosis associated with the pathophysiological features of the disease. Statistical data on the prevalence of this pathology in the world and in the Russian Federation are presented. The mechanisms of sputum formation and disorders of the mucociliary apparatus, leading to the accumulation of viscous bronchopulmonary secret in cystic fibrosis, are considered. The principles of the relationship between the rheological properties of sputum and the formation of inflammation in the lungs with the addition of a concomitant specific microflora in the bronchopulmonary system in patients with cystic fibrosis are presented. Describes the opportunities for biochemical studies of sputum of patients with this pathology: determining the activity of enzymes (myeloperoxidase), the content of proteinase inhibitors (α2-macroglobulin and α1-antitrypsin) and proinflammatory cytokines (IL-8 and TNFa), concentrations of iron and ferriferous proteins (lactoferrin and ferritin), which makes biochemical studies of sputum available, non-invasive, quick and cost-effective method of diagnosis, which can be widely used as an auxiliary laboratory method and makes it possible to use these metabolites as diagnostic markers to assess the severity of inflammation and infection of the lower respiratory tract and predict the development of respiratory complications in patients with cystic fibrosis.

PMID: 30912880 [PubMed - in process]

Isolated pulmonary interstitial glycogenosis associated with alveolar growth abnormalities: A long-term follow-up study.

Pediatr Pulmonol. 2019 Mar 25;:

Authors: Sardón O, Torrent-Vernetta A, Rovira-Amigo S, Dishop MK, Ferreres JC, Navarro A, Corcuera P, Korta-Murua J, Peña PG, Pérez-Belmonte E, Villares A, Camats N, Fernández-Cancio M, Carrascosa A, Pérez-Yarza EG, Moreno-Galdó A

Abstract
INTRODUCTION: Pulmonary interstitial glycogenosis (PIG) is a rare infant interstitial lung disease characterized by an increase in the number of interstitial mesenchymal cells, presenting as enhanced cytoplasmic glycogen, and is considered to represent the expression of an underlying lung development disorder.
METHODS: This study describes the clinical, radiological, and functional characteristics and long-term outcomes (median 12 years) of nine infants diagnosed with isolated PIG associated with alveolar simplification in the absence of other diseases.
RESULTS: All patients presented with tachypnea. Additionally, seven patients had breathing difficulties and hypoxemia. Abnormalities in chest-computerized tomography (CT) with a pattern of ground-glass opacity, septal thickening, and air trapping were observed in all individuals, with images suggesting abnormal alveolar growth (parenchymal bands and architectural distortion). All lung biopsies showed alveolar simplification associated with an increased number of interstitial cells, which appeared as accumulated cytoplasmic glycogen. In the follow-up, all patients were asymptomatic. The respiratory function test was normal in only two patients. Five children showed an obstructive pattern, and two children showed a restrictive pattern. Chest-CT, performed after an average of 6.5 years since the initial investigation, revealed a partial improvement of the ground-glass opacity pattern; however, relevant alterations persisted.
CONCLUSION: Although the patients with PIG in the absence of other associated pathologies had a good clinical outcome, significant radiographic alterations and sequelae in lung function were still observed after a median follow-up of 12 years, suggesting that PIG is a marker of some other persistent abnormalities in lung growth, which have effects beyond the symptomatic period.

PMID: 30912317 [PubMed - as supplied by publisher]

Ivacaftor drug desensitization.

Pediatr Pulmonol. 2019 Mar 25;:

Authors: Patterson A, Autry E, Kuhn R, Wurth M

PMID: 30912311 [PubMed - as supplied by publisher]

In Vitro Activity of a Novel Glycopolymer against Biofilms of Burkholderia cepacia Complex Cystic Fibrosis Clinical Isolates.

Antimicrob Agents Chemother. 2019 Mar 25;:

Authors: Narayanaswamy VP, Duncan AP, LiPuma JJ, Wiesmann WP, Baker SM, Townsend SM

Abstract
Burkholderia cepacia complex (Bcc) lung infections in cystic fibrosis (CF) patients are often associated with a steady decline in lung function and death. The formation of biofilms and inherent multi-drug resistance are virulence factors associated with Bcc infection and contribute to increased risk of mortality in CF patients. New therapeutic strategies targeting bacterial biofilms are anticipated to enhance antibiotic penetration and facilitate resolution of infection. Poly (acetyl, arginyl) glucosamine (PAAG), is a cationic glycopolymer therapeutic being developed to directly target biofilm integrity. In this study, thirteen isolates from 7 species were examined including; B. multivorans, B. cenocepacia, B. gladioli, B. dolosa, B. vietnamiensis, and B. cepacia These isolates were selected for their resistance to standard clinical antibiotics and their ability to form biofilms in vitro. Biofilm biomass was quantitated using static tissue culture plate (TCP) biofilm methods and minimum biofilm eradication concentration (MBEC) assay. Confocal laser scanning microscopy (CLSM) visualized biofilm removal by PAAG during treatment. Both TCP and MBEC methods demonstrated a significant dose-dependent relationship with regard to biofilm removal by 50-200μg/ml PAAG following 1-hour treatment (p<0.01). A significant reduction in biofilm thickness was observed following 10-minute treatment of Bcc biofilms with PAAG compared to vehicle control (p<0.001) in TCP, MBEC, and CLSM analysis. PAAG also rapidly permeabilizes bacteria within the first 10 minutes of treatment. Glycopolymers such as PAAG, are a new class of large-molecule therapeutics that support the treatment of recalcitrant Bcc biofilm.

PMID: 30910901 [PubMed - as supplied by publisher]

[A one-thousand-kilometre bike ride in aid of cystic fibrosis].

Rev Infirm. 2019 Jan;68(247):43

Authors: Chevardé L

Abstract
Louis is a 21-year-old recently graduated nurse now working in a medical-educational institute. During his initial training, he spent a summer cycling across France with another student nurse, to promote the cause of patients suffering from cystic fibrosis. This article describes his breath-taking adventure!

PMID: 30910120 [PubMed - in process]