Cystic Fibrosis

First and second wave of SARS-CoV2 in Italian Cystic Fibrosis patients: Data from Italian Cystic Fibrosis Registry.

Tue, 2021-02-09 02:22
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First and second wave of SARS-CoV2 in Italian Cystic Fibrosis patients: Data from Italian Cystic Fibrosis Registry.

J Cyst Fibros. 2021 Jan 26;:

Authors: Padoan R, Salvatore M, Carnovale V, Salvatore D, Quattrucci S, Taruscio D, Floridia G, Amato A, Ferrari G, Campagna G

PMID: 33549520 [PubMed - as supplied by publisher]

Categories: Literature Watch

Extended-culture and culture-independent molecular analysis of the airway microbiota in cystic fibrosis following CFTR modulation with ivacaftor.

Tue, 2021-02-09 02:22
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Extended-culture and culture-independent molecular analysis of the airway microbiota in cystic fibrosis following CFTR modulation with ivacaftor.

J Cyst Fibros. 2021 Feb 03;:

Authors: Einarsson GG, Ronan NJ, Mooney D, McGettigan C, Mullane D, NiChroinin M, Shanahan F, Murphy DM, McCarthy M, McCarthy Y, Eustace JA, Gilpin DF, Elborn JS, Plant BJ, Tunney MM

Abstract
BACKGROUND: Treatment with Ivacaftor provides a significant clinical benefit in people with cystic fibrosis (PWCF) with the class III G551D-CFTR mutation. This study determined the effect of CFTR modulation with ivacaftor on the lung microbiota in PWCF.
METHODS: Using both extended-culture and culture-independent molecular methods, we analysed the lower airway microbiota of 14 PWCF, prior to commencing ivacaftor treatment and at the last available visit within the following year. We determined total bacterial and Pseudomonas aeruginosa densities by both culture and qPCR, assessed ecological parameters and community structure and compared these with biomarkers of inflammation and clinical outcomes.
RESULTS: Significant improvement in FEV1, BMI, sweat chloride and levels of circulating inflammatory biomarkers were observed POST-ivacaftor treatment. Extended-culture demonstrated a higher density of strict anaerobic bacteria (p = 0.024), richness (p = 1.59*10-4) and diversity (p = 0.003) POST-treatment. No significant difference in fold change was observed by qPCR for either total bacterial 16S rRNA copy number or P. aeruginosa density for oprL copy number with treatment. Culture-independent (MiSeq) analysis revealed a significant increase in richness (p = 0.03) and a trend towards increased diversity (p = 0.07). Moreover, improvement in lung function, richness and diversity displayed an inverse correlation with the main markers of inflammation (p < 0.05).
CONCLUSIONS: Following treatment with ivacaftor, significant improvements in clinical parameters were seen. Despite modest changes in overall microbial community composition, there was a shift towards a bacterial ecology associated with less severe CF lung disease. Furthermore, a significant correlation was observed between richness and diversity and levels of circulating inflammatory markers.

PMID: 33549519 [PubMed - as supplied by publisher]

Categories: Literature Watch

Urinary stone disease prevalence and associations in cystic fibrosis.

Sun, 2021-02-07 07:17
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Urinary stone disease prevalence and associations in cystic fibrosis.

Urolithiasis. 2021 Feb 06;:

Authors: Wright JF, Craig WY, Lucas FL, Goldfarb DS, Zuckerman JB, Taylor EN

Abstract
Cystic fibrosis (CF) may predispose patients to urinary stone disease (USD), but reported prevalence of USD in patients with CF in previous small studies is variable. To date, analysis of risk factors for USD within the CF population has been limited. We studied 29,396 patients in the Cystic Fibrosis Foundation Patient Registry to calculate age and sex-stratified prevalence of USD. For adult patients, we examined age and multivariable-adjusted cross-sectional associations between demographic and clinical factors, CFTR mutation class, and prevalent USD. Prevalence of USD was 0.4% (95% CI 0.3-0.5%) under age 18 years, 3.1% (2.7-3.6%) at 18-24 years, 6.4% (5.8-7.1%) at 25-34 years, 7.5% (6.5-8.5%) at 35-44 years, and 6.7% (5.8-7.8%) at 45 years and older. Prevalence for women was higher than men at younger (< 45 years) but not older ages (P value for interaction < 0.0005). Multivariable odds of prevalent USD were significantly increased for severe CFTR mutations, OR 1.53 (1.14-2.06), diabetes, OR 1.24 (1.03-1.50), hypertension, OR 1.58 (1.29-1.93), and chronic macrolide therapy, OR 1.27 (1.07-1.52). BMI was not associated with USD. USD prevalence in CF is similar to that in the general population. With the exception of BMI, known risk factors for USD in the general population also appear to be important for patients with CF. We identified several novel associations in CF patients, including greater prevalence of USD in individuals with severe CFTR mutations and among young women.

PMID: 33547925 [PubMed - as supplied by publisher]

Categories: Literature Watch

Formulation and In Vitro and In Silico Characterization of "Nano-in-Micro" Dry Powder Inhalers Containing Meloxicam.

Sun, 2021-02-07 07:17
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Formulation and In Vitro and In Silico Characterization of "Nano-in-Micro" Dry Powder Inhalers Containing Meloxicam.

Pharmaceutics. 2021 Feb 03;13(2):

Authors: Party P, Bartos C, Farkas Á, Szabó-Révész P, Ambrus R

Abstract
Pulmonary delivery has high bioavailability, a large surface area for absorption, and limited drug degradation. Particle engineering is important to develop inhalable formulations to improve the therapeutic effect. In our work, the poorly water-soluble meloxicam (MX) was used as an active ingredient, which could be useful for the treatment of non-small cell lung cancer, cystic fibrosis, and chronic obstructive pulmonary disease. We aimed to produce inhalable "nano-in-micro" dry powder inhalers (DPIs) containing MX and additives (poly-vinyl-alcohol, leucine). We targeted the respiratory zone with the microcomposites and reached a higher drug concentration with the nanonized active ingredient. We did the following investigations: particle size analysis, morphology, density, interparticular interactions, crystallinity, in vitro dissolution, in vitro permeability, in vitro aerodynamics (Andersen cascade impactor), and in silico aerodynamics (stochastic lung model). We worked out a preparation method by combining wet milling and spray-drying. We produced spherical, 3-4 µm sized particles built up by MX nanoparticles. The increased surface area and amorphization improved the dissolution and diffusion of the MX. The formulations showed appropriate aerodynamical properties: 1.5-2.4 µm MMAD and 72-76% fine particle fraction (FPF) values. The in silico measurements proved the deposition in the deeper airways. The samples were suitable for the treatment of local lung diseases.

PMID: 33546452 [PubMed - as supplied by publisher]

Categories: Literature Watch

Prognosis-Based Early Intervention Strategies to Resolve Exacerbation and Progressive Lung Function Decline in Cystic Fibrosis.

Sun, 2021-02-07 07:17
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Prognosis-Based Early Intervention Strategies to Resolve Exacerbation and Progressive Lung Function Decline in Cystic Fibrosis.

J Pers Med. 2021 Feb 03;11(2):

Authors: Vij N

Abstract
Cystic fibrosis (CF) is a genetic disease caused by a mutation(s) in the CF transmembrane regulator (CFTR), where progressive decline in lung function due to recurring exacerbations is a major cause of mortality. The initiation of chronic obstructive lung disease in CF involves inflammation and exacerbations, leading to mucus obstruction and lung function decline. Even though clinical management of CF lung disease has prolonged survival, exacerbation and age-related lung function decline remain a challenge for controlling the progressive lung disease. The key to the resolution of progressive lung disease is prognosis-based early therapeutic intervention; thus, the development of novel diagnostics and prognostic biomarkers for predicting exacerbation and lung function decline will allow optimal management of the lung disease. Hence, the development of real-time lung function diagnostics such as forced oscillation technique (FOT), impulse oscillometry system (IOS), and electrical impedance tomography (EIT), and novel prognosis-based intervention strategies for controlling the progression of chronic obstructive lung disease will fulfill a significant unmet need for CF patients. Early detection of CF lung inflammation and exacerbations with the timely resolution will not only prolong survival and reduce mortality but also improve quality of life while reducing significant health care costs due to recurring hospitalizations.

PMID: 33546140 [PubMed - as supplied by publisher]

Categories: Literature Watch

Assessment of Platelet Thrombus Formation under Flow Conditions in Adult Patients with COVID-19: An Observational Study.

Sat, 2021-02-06 12:47
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Assessment of Platelet Thrombus Formation under Flow Conditions in Adult Patients with COVID-19: An Observational Study.

Thromb Haemost. 2021 Feb 05;:

Authors: Ghirardello S, Lecchi A, Artoni A, Panigada M, Aliberti S, Scalambrino E, La Marca S, Boscarino M, Gramegna A, Properzi P, Abruzzese C, Blasi F, Grasselli G, Mosca F, Tripodi A, Peyvandi F

Abstract
BACKGROUND:  Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation, which may dysregulate platelet function. Total Thrombus-Formation Analysis System (T-TAS) is a flow-chamber device that analyses platelet-mediated thrombus formation in capillary channels through the following parameters: (1) the area under the flow-pressure curve (AUC), (2) occlusion start time (OST), time needed to reach OST, and (3) occlusion time (OT), time needed to reach the occlusion pressure.
METHODS AND FINDINGS:  Sixty-one COVID-19 patients admitted to intensive, subintensive, and low intensive care were prospectively enrolled according to the time of admission: group A (up to 8 days) (n = 18); group B (from 9 to 21 days) (n = 19), and group C ( > 21 days) (n = 24). T-TAS measurements were performed at enrolment and after 7 days. Median OST was similar among groups. AUC was lower in group A compared to B (p = 0.001) and C (p = 0.033). OT was longer in group A compared to B (p = 0.001) and C (p = 0.028). Platelet count (PC) was higher in group B compared to A (p = 0.024). The linear regression showed that OT and AUC were independent from PC in group A (OT: 0.149 [95% confidence interval [CI]: -0.326 to 0.624], p = 0.513 and AUC: 0.005 [95% CI: -0.008 to 0.017], p = 0,447). In contrast, in group B, PC was associated with OT (-0.019 [-0.028 to 0.008], p = 0.023) and AUC (0.749 [0.358-1.139], p = 0,015), similarly to group C. Conversely, patients with different illness severity had similar T-TAS parameters.
CONCLUSION:  COVID-19 patients display an impaired platelet thrombus formation in the early phase of the disease compared to later stages and controls, independently from illness severity.

PMID: 33545735 [PubMed - as supplied by publisher]

Categories: Literature Watch

Multidisciplinary approach to patients with manifestations and pulmonary complications of cystic fibrosis.

Sat, 2021-02-06 12:47
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Multidisciplinary approach to patients with manifestations and pulmonary complications of cystic fibrosis.

Rom J Morphol Embryol. 2020 Apr-Jun;61(2):397-406

Authors: Biciuşcă V, Petrescu IO, Singer CE, Oancea AG, Petrescu AM, Stan IS, Durand P, Taisescu CI, Dumitrescu D, Dobrescu MA, Udriştoiu I, Tudoraşcu DR, Petrescu F

Abstract
Cystic fibrosis (CF) is a genetic disease, with autosomal recessive transmission, multisystemic, characterized by a remarkable clinical polymorphism and significant lethal prospective. Respiratory manifestations dominate the clinical picture, being present in all patients. The aim of the paper was to analyze the incidence of clinical manifestations, especially respiratory ones, as well as the contribution of interdisciplinary consultations to the positive diagnosis of CF, in a group of 16 patients who were hospitalized and treated in the IInd Pediatric Clinic and IInd Medical Clinic of the Emergency County Hospital, Craiova, Romania, in a period of 20 years. The 16 patients diagnosed with and treated of CF had all shown increased values of sweat chloride concentration of over 60 mmol∕L. The main symptoms and clinical signs encountered in these patients were cough (75%), sputum (62.5%), dyspnea (50%), wheezing (50%), stature hypotrophy (100%), pallor (37.5%), cyanosis (25%). All 16 patients had an acute exacerbation of chronic pulmonary disease. Of the total hospitalizations, the death was recorded only in the case of one female patient. The association of some clinical aspects specific with a positive result of the sweat test or the presence of the two pathological alleles made room for determining a positive diagnosis. The multisystemic nature of this disease requires a multidisciplinary approach to these patients. Histopathologically, there was a correspondence between lung morphological lesions and the results of imaging investigations.

PMID: 33544791 [PubMed - as supplied by publisher]

Categories: Literature Watch

A Prospective Study of the Effects of Sex Hormones on Lung Function and Inflammation in Women with Cystic Fibrosis.

Sat, 2021-02-06 12:47
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A Prospective Study of the Effects of Sex Hormones on Lung Function and Inflammation in Women with Cystic Fibrosis.

Ann Am Thorac Soc. 2021 Feb 05;:

Authors: Holtrop M, Heltshe S, Shabanova V, Keller A, Schumacher L, Fernandez L, Jain R

Abstract
RATIONALE: Epidemiologic studies demonstrate worse outcomes in women with cystic fibrosis (CF) than men. Women are colonized earlier with respiratory pathogens and have increased rates of pulmonary exacerbations post-puberty and near ovulation. The etiology of this disparity is unclear, but sex hormones may contribute to these differences.
OBJECTIVES: We sought to explore if natural hormonal fluctuations and hormonal contraception associate with changes in lung function, respiratory symptoms, or inflammatory markers.
METHODS: We prospectively followed women with CF who were not on hormonal contraceptives and reported regular menstrual cycles. We captured study visits at points that corresponded to menses, ovulation, and the luteal phase. A subset of subjects were subsequently placed on a standard oral estrogen/progesterone combination contraceptive pill, ethinyl estradiol/norethindrone (Loestrin), and re-evaluated. Measurements included lung function, symptom questionnaires, sweat tests, blood for hormone levels, and sputum for inflammatory markers, bacterial density, and cytology.
RESULTS: Twenty-three women participated in this study. Hormone levels were as expected on and off hormonal contraception. At times of peak estrogen (ovulation), there was a significant increase in sputum pro-inflammatory cytokines (neutrophil free elastase) and a corresponding pattern of decrease in lung function. Pro-inflammatory cytokines (IL-8, TNF-α, neutrophil free elastase) improved when placed on hormone contraception.
CONCLUSIONS: Our results show that there are potentially important fluctuations in inflammatory biomarkers in the lungs that correlate with changes in lung function in women with CF. Larger studies evaluating the impact of sex hormones on airway inflammation and immune response are necessary to better understand the clinical impact of these responses. Clinical trial registered with ClinicalTrials.gov (NCT02036879).

PMID: 33544657 [PubMed - as supplied by publisher]

Categories: Literature Watch

The effects of the addition of a new airway clearance device to chest physiotherapy in children with cystic fibrosis pulmonary exacerbations.

Sat, 2021-02-06 12:47
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The effects of the addition of a new airway clearance device to chest physiotherapy in children with cystic fibrosis pulmonary exacerbations.

J Mother Child. 2021 Jan 26;:

Authors: Walicka-Serzysko K, Postek M, Jeneralska N, Cichocka A, Milczewska J, Sands D

Abstract
BACKGROUND: Chest physiotherapy plays a crucial role in managing cystic fibrosis, especially during pulmonary exacerbations. This study evaluated the effects of adding a new airway clearance device to chest physiotherapy in subjects with cystic fibrosis hospitalised due to pulmonary exacerbations.
METHODS: This prospective open-label study was carried out at the Pediatric Cystic Fibrosis Centre in Poland between October 2017 and August 2018. Cystic fibrosis patients aged 10 to 18 years who were admitted to the hospital and required intravenous antibiotic therapy due to pulmonary exacerbations were consecutively allocated (1:1) to either chest physiotherapy alone or chest physiotherapy with a new airway clearance device (Simeox; PhysioAssist). Patients performed spirometry and multiple-breath nitrogen washout for lung clearance index assessment upon admission and prior to discharge.
RESULTS: Forty-eight cystic fibrosis patients were included (24 in each group). Spirometry parameters in both groups improved significantly after intravenous antibiotic therapy. A significant improvement in the maximum expiratory flow at 25% of forced vital capacity was observed only in the group with a new airway clearance device (p < 0.01 vs. baseline). Trends towards a lower lung clearance index ratio were similar in both groups. No adverse events were observed in either group.
CONCLUSIONS: Spirometry parameters increased significantly in cystic fibrosis patients treated for pulmonary exacerbations with intravenous antibiotic therapy and intensive chest physiotherapy. The new airway clearance device was safe and well tolerated when added to chest physiotherapy and may be another option for the treatment of pulmonary exacerbation in cystic fibrosis.

PMID: 33544556 [PubMed - as supplied by publisher]

Categories: Literature Watch

A case of interference in testosterone, DHEA-S and progesterone measurements by second generation immunoassays.

Sat, 2021-02-06 12:47
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A case of interference in testosterone, DHEA-S and progesterone measurements by second generation immunoassays.

Clin Chem Lab Med. 2021 Feb 01;:

Authors: Cresta F, Arcuri L, Bianchin S, Castellani C, Casciaro R, Cavedagna TM, Maghnie M, Barco S, Cangemi G

PMID: 33544463 [PubMed - as supplied by publisher]

Categories: Literature Watch

Mycoplasma pneumoniae: a pathogen with unsolved therapeutic problems.

Sat, 2021-02-06 12:47
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Mycoplasma pneumoniae: a pathogen with unsolved therapeutic problems.

Expert Opin Pharmacother. 2021 Feb 05;:1-10

Authors: Esposito S, Argentiero A, Gramegna A, Principi N

Abstract
INTRODUCTION: Despite the amount of new information, the most effective approach for the diagnosis and treatment of Mycoplasma pneumoniae infections is not established. In this narrative review the pharmacological options for macrolide-resistant (ML) M. pneumoniae infections in children are discussed.
AREAS COVERED: Despite significant improvement in the diagnosis and in the definition of diseases potentially associated with this pathogen, not all the problems related to M. pneumoniae infection are solved. True epidemiology of M. pneumoniae diseases and the real role of this pathogen in extra-respiratory manifestations is still unestablished. This reflects on therapy. It is not known whether antibiotics are really needed in all the cases, independently of severity and localization. The choice of antibiotic therapy is debated as it is not known whether ML resistance has clinical relevance. Moreover, not precisely defined is the clinical importance of corticosteroids for improvement of severe cases, including those associated with ML-resistant strains.
EXPERT OPINION: Improvement in M. pneumoniae identification is mandatory to reduce antibiotics overuse , especially in the presence of ML-resistant strains. Priority for future studies includes the evaluation of the true benefit of therapeutic approaches including corticosteroids in patients with severe CAP and in those with extra-respiratory M. pneumoniae diseases.

PMID: 33544008 [PubMed - as supplied by publisher]

Categories: Literature Watch

Recent progress, challenges, and opportunities for wearable biochemical sensors for sweat analysis.

Sat, 2021-02-06 12:47
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Recent progress, challenges, and opportunities for wearable biochemical sensors for sweat analysis.

Sens Actuators B Chem. 2021 Apr 01;332:

Authors: Ghaffari R, Rogers JA, Ray TR

Abstract
Sweat is a promising, yet relatively unexplored biofluid containing biochemical information that offers broad insights into the underlying dynamic metabolic activity of the human body. The rich composition of electrolytes, metabolites, hormones, proteins, nucleic acids, micronutrients, and exogenous agents found in sweat dynamically vary in response to the state of health, stress, and diet. Emerging classes of skin-interfaced wearable sensors offer powerful capabilities for the real-time, continuous analysis of sweat produced by the eccrine glands in a manner suitable for use in athletics, consumer wellness, military, and healthcare industries. This perspective examines the rapid and continuous progress of wearable sweat sensors through the most advanced embodiments that address the fundamental challenges currently restricting widespread deployment. It concludes with a discussion of efforts to expand the overall utility of wearable sweat sensors and opportunities for commercialization, in which advances in biochemical sensor technologies will be critically important.

PMID: 33542590 [PubMed]

Categories: Literature Watch

Membrane-destabilizing ionizable phospholipids for organ-selective mRNA delivery and CRISPR-Cas gene editing.

Sat, 2021-02-06 12:47
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Membrane-destabilizing ionizable phospholipids for organ-selective mRNA delivery and CRISPR-Cas gene editing.

Nat Mater. 2021 Feb 04;:

Authors: Liu S, Cheng Q, Wei T, Yu X, Johnson LT, Farbiak L, Siegwart DJ

Abstract
Endosomal escape remains a fundamental barrier hindering the advancement of nucleic acid therapeutics. Taking inspiration from natural phospholipids that comprise biological membranes, we report the combinatorial synthesis of multi-tailed ionizable phospholipids (iPhos) capable of delivering messenger RNA or mRNA/single-guide RNA for gene editing in vivo. Optimized iPhos lipids are composed of one pH-switchable zwitterion and three hydrophobic tails, which adopt a cone shape in endosomal acidic environments to facilitate membrane hexagonal transformation and subsequent cargo release from endosomes. Structure-activity relationships reveal that iPhos chemical structure can control in vivo efficacy and organ selectivity. iPhos lipids synergistically function with various helper lipids to formulate multi-component lipid nanoparticles (called iPLNPs) for selective organ targeting. Zwitterionic, ionizable cationic and permanently cationic helper lipids enable tissue-selective mRNA delivery and CRISPR-Cas9 gene editing in spleen, liver and lungs (respectively) following intravenous administration. This rational design of functional phospholipids demonstrates substantial value for gene editing research and therapeutic applications.

PMID: 33542471 [PubMed - as supplied by publisher]

Categories: Literature Watch

Eradication success for non-tuberculous mycobacteria in children with cystic fibrosis.

Sat, 2021-02-06 12:47
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Eradication success for non-tuberculous mycobacteria in children with cystic fibrosis.

Eur Respir J. 2021 Feb 04;:

Authors: Hughes DA, Bokobza I, Carr SB

PMID: 33542059 [PubMed - as supplied by publisher]

Categories: Literature Watch

Determinants of lung disease progression measured by lung clearance index in children with cystic fibrosis.

Sat, 2021-02-06 12:47
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Determinants of lung disease progression measured by lung clearance index in children with cystic fibrosis.

Eur Respir J. 2021 Feb 04;:

Authors: Stanojevic S, Davis SD, Perrem L, Shaw M, Retsch-Bogart G, Davis M, Jensen R, Clem CC, Isaac SM, Guido J, Jara S, France L, McDonald N, Solomon M, Sweezey N, Grasemann H, Waters V, Sanders DB, Ratjen FA

Abstract
BACKGROUND: The lung clearance index (LCI) measured by the multiple breath washout (MBW) test is sensitive to early lung disease in children with cystic fibrosis (CF). While LCI worsens during the preschool years in CF, there is limited evidence to clarify whether this continues during the early school age years, and whether the trajectory of disease progression as measured by LCI is modifiable.
METHODS: A cohort of children (healthy (HC) and CF) previously studied for 12 months as preschoolers were followed during school age (5-10 years). LCI was measured every 3 months for a period of 24 months using the Exhalyzer® D MBW nitrogen washout device. Linear mixed effects regression was used to model changes in LCI over time.
RESULTS: A total of 582 MBW measurements in 48 healthy subjects and 845 measurements in 64 CF subjects were available. The majority of children with CF had elevated LCI at the first preschool and first school age visits (57.8% (37/64)), whereas all but six had normal forced expiratory volume in 1 s (FEV1) values at the first school age visit. During school age years, the course of disease was stable (-0.02 units·year-1 (95% CI -0.14; 0.10). LCI measured during preschool years, as well as the rate of LCI change during this time period, were important determinants of LCI and FEV1, at school age.
CONCLUSION: Preschool LCI was a major determinant of school age LCI; these findings further support that the preschool years are critical for early intervention strategies.

PMID: 33542049 [PubMed - as supplied by publisher]

Categories: Literature Watch

Complete Genome Sequence of Burkholderia gladioli Phage Maja.

Sat, 2021-02-06 12:47
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Complete Genome Sequence of Burkholderia gladioli Phage Maja.

Microbiol Resour Announc. 2021 Feb 04;10(5):

Authors: Yu Z, Yao G, Vizoso-Pinto MG, Sun L, Young R, Gonzalez C, Liu M

Abstract
Burkholderia gladioli is a Gram-negative bacterium associated with cystic fibrosis infections. Here, we describe the genome sequence of B. gladioli phage Maja. Maja is most related to another Burkholderia phage, BcepF1, and may be a temperate phage, despite the absence of repressor or integrase homologs in its genome sequence.

PMID: 33541882 [PubMed]

Categories: Literature Watch

Pseudomonas aeruginosa Resistance to Bacteriophages and Its Prevention by Strategic Therapeutic Cocktail Formulation.

Sat, 2021-02-06 12:47
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Pseudomonas aeruginosa Resistance to Bacteriophages and Its Prevention by Strategic Therapeutic Cocktail Formulation.

Antibiotics (Basel). 2021 Feb 02;10(2):

Authors: Vaitekenas A, Tai AS, Ramsay JP, Stick SM, Kicic A

Abstract
Antimicrobial resistance poses a significant threat to modern healthcare as it limits treatment options for bacterial infections, particularly impacting those with chronic conditions such as cystic fibrosis (CF). Viscous mucus accumulation in the lungs of individuals genetically predisposed to CF leads to recurrent bacterial infections, necessitating prolonged antimicrobial chemotherapy. Pseudomonas aeruginosa infections are the predominant driver of CF lung disease, and airway isolates are frequently resistant to multiple antimicrobials. Bacteriophages, or phages, are viruses that specifically infect bacteria and are a promising alternative to antimicrobials for CF P. aeruginosa infections. However, the narrow host range of P. aeruginosa-targeting phages and the rapid evolution of phage resistance could limit the clinical efficacy of phage therapy. A promising approach to overcome these issues is the strategic development of mixtures of phages (cocktails). The aim is to combine phages with broad host ranges and target multiple distinct bacterial receptors to prevent the evolution of phage resistance. However, further research is required to identify and characterize phage resistance mechanisms in CF-derived P. aeruginosa, which differ from their non-CF counterparts. In this review, we consider the mechanisms of P. aeruginosa phage resistance and how these could be overcome by an effective future phage therapy formulation.

PMID: 33540528 [PubMed]

Categories: Literature Watch

Development and in vitro characterization of a novel pMDI diclofenac formulation as an inhalable anti-inflammatory therapy for cystic fibrosis.

Fri, 2021-02-05 06:17

Development and in vitro characterization of a novel pMDI diclofenac formulation as an inhalable anti-inflammatory therapy for cystic fibrosis.

Int J Pharm. 2021 Feb 01;:120319

Authors: Sheikh Z, Gomes Dos Reis L, Bradbury P, Meneguzzo G, Scalia S, Young PM, Xin Ong H, Traini D

Abstract
Anti-inflammatory treatment options for cystic fibrosis (CF) patients are currently limited and as such, there is an imperative need to develop new anti-inflammatory agents to reduce the persistent inflammation present within CF lungs. This study explored the potential of Diclofenac (DICLO) as a novel inhaled anti-inflammatory drug for CF treatment. The anti-inflammatory activity of DICLO on an air-liquid interface (ALI) cell culture model of healthy (NuLi-1) and CF (CuFi-1) airways showed a significant reduction in the secretion of pro-inflammatory cytokines, IL-6 and IL-8. Therefore, pressurized metered dose inhaler (pMDI) DICLO formulations were developed to allow targeted DICLO delivery to CF airways. As such, two pMDI DICLO formulations with varying ethanol concentrations: 5% (w/w) equating to 150 µg of DICLO per dose (Low dose), and 15% (w/w) equating to 430 µg of DICLO per dose (High dose) were developed and characterized to determine the optimum formulation. The Low dose pMDI DICLO formulation showed a significantly smaller particle diameter with uniform distribution resulting in a greater aerosol performance when compared to High dose formulation. Consequently, the Low dose pMDI DICLO formulation was further evaluated in terms of in vitro transport characteristics and anti-inflammatory activity. Importantly, the DICLO pMDI displayed anti-inflammatory activity in both healthy and CF in vitro models, highlighting the potential of an aerosolized low-dose DICLO formulation as a promising inhaled anti-inflammatory therapy for CF treatment.

PMID: 33540036 [PubMed - as supplied by publisher]

Categories: Literature Watch

Telemedicine Use and Health-related Concerns of Patients with Chronic Conditions During COVID-19: A Survey of Members of Online Health Communities.

Fri, 2021-02-05 06:17

Telemedicine Use and Health-related Concerns of Patients with Chronic Conditions During COVID-19: A Survey of Members of Online Health Communities.

J Med Internet Res. 2021 Feb 01;:

Authors: Horrell LN, Hayes S, Herbert LB, MacTurk K, Lawhon L, Valle CG, Bhowmick A

Abstract
BACKGROUND: It has been widely communicated that individuals with underlying health conditions are at higher risk of severe disease due to COVID-19 than healthy peers. As social distancing measures continue during the COVID-19 pandemic, experts encourage individuals with underlying conditions to engage in telehealth appointments to maintain continuity of care while minimizing risk exposure. To date, however, little information has been provided regarding telehealth uptake among this high-risk population.
OBJECTIVE: The objective of this study was to describe the telehealth use, resource needs, and information sources of individuals with chronic conditions during the COVID-19 pandemic. Secondary objectives include exploring differences in telehealth use by sociodemographic characteristics.
METHODS: Data for this study were collected through electronic survey distributed between May 12-14, 2020 to members of 26 online health communities for individuals with chronic disease. Descriptive statistics were run to explore telehealth use, support needs, and information sources, and Z-tests were run to assess differences in sociodemographic factors and information and support needs among those who did and did not use telehealth services.
RESULTS: Among the 2,210 respondents, 1,073 (49%) reported engaging in telehealth in the past 4 months. Higher proportions of women engaged in telehealth than men (50% vs. 43%, P = .007), and a higher proportion of those earning household incomes over $100,000 engaged in telehealth than those earning less than $30,000 (53% vs. 45%, P = .003). While 59% of those under 40 years old, and 54 of those ages 40-55, used telehealth, ageing populations were less likely to do so, with only 45% of individuals 56+ reporting telehealth use (P <.0005 and P =.001, respectively). Patients with cystic fibrosis, lupus, and ankylosing spondylitis recorded the highest proportions of individuals using telehealth when compared to those with other diagnoses. In total, 60% of participants either looked up information about the virus online or planned to in the future, and when asked what information or support would be most helpful right now, over half (n = 1,151, 52%) responded "understanding how COVID-19 affects people with my health condition."
CONCLUSIONS: Nearly half of the study sample reported participating in telehealth in the past 4 months. Future efforts to engage individuals with underlying medical conditions in telehealth should focus on outreach to men, members of lower income households, and aging populations. These results may help inform and refine future health communications to further engage this at-risk population in telehealth as the pandemic continues.

PMID: 33539307 [PubMed - as supplied by publisher]

Categories: Literature Watch

The Effects of Nebulizer Hygiene Training on the Practices of Cystic Fibrosis Patients and Caregivers.

Fri, 2021-02-05 06:17

The Effects of Nebulizer Hygiene Training on the Practices of Cystic Fibrosis Patients and Caregivers.

Pediatr Pulmonol. 2021 Feb 04;:

Authors: Yegit CY, Ergenekon AP, Mursaloglu HH, Cenk M, Uzunoglu BS, Tastan G, Gokdemir Y, Eralp EE, Karakoc F, Nasr SZ, Karadag B

Abstract
BACKGROUND: Nebulizers can be contaminated with microorganisms and may be a source of infection in the lower airways in patients with cystic fibrosis (CF).
OBJECTIVE: Primary aim of this study was to determine the level of knowledge regarding nebulizer hygiene and adherence to CF Foundation Infection Prevention&Control (IP&C) measures of CF patients in our center. We also evaluated the effect of a standardized training program on nebulizer cleaning and disinfection practises with pre and posttest.
METHODS: Caregivers of 173 CF patients followed at Marmara University CF Center filled a questionnaire (pretest) regarding nebulizer hygiene and received didactic education including pictures and videos based on the CFF IP&C guidelines, patients were also provided educational materials. Posttest was performed 1-3 months after the education session.
RESULTS: Following standardized training, usage of appropriate methods according to CFF IP&C guidelines improved significantly. Frequency of nebulizer cleaning after each use increased from 58.4% to 78% (p<0.01) and disinfection frequency after each/daily usage increased from 33.6% to 75.7% (p<0.01). Additionally, methods of cleaning and storage of the nebulizer, also improved significantly (p<0.01, p<0.01).
CONCLUSION: Education was highly effective to increase the rate of proper practices for nebulizer hygiene. The necessity of cleaning, disinfection, careful drying, correct storage of the nebulizer parts and changing the nebulizer equipment within recommended time should be emphasized to CF families regularly. This article is protected by copyright. All rights reserved.

PMID: 33538406 [PubMed - as supplied by publisher]

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