Effect of nebulised BromAc® on rheology of artificial sputum: relevance to muco-obstructive respiratory diseases including COVID-19

Respiratory diseases such as cystic fibrosis, COPD, bronchiectasis asthma and COVID-19 are difficult to treat owing to viscous secretions in the airways that evade mucocilliary clearance. Since earlier studies have shown success with BromAc as mucolytic agent for treating a rare disease known as pseudomyxoma peritonei (PMP), we tested the formulation on two gelatinous airway representative sputa models, in order to determine whether similar efficacy exist. The sputum (1.5 ml) lodged in an endotracheal tube was treated to aerosolised N-acetylcysteine, bromelain, or their combination (BromAc) using a nebuliser with 6.0 ml of the agents in phosphate buffer saline, over 25 min. Controls received phosphate buffer saline. The dynamic viscosity was measured before and after treatment using a capillary tube method, whilst the sputum flow (ml/sec) was assessed using a 0.5 ml pipette. Finally, the sequestered agents (concentration) in the sputa after treatment were quantified using standard bromelain and N-acetylcysteine chromogenic assays. Results indicated that bromelain and N-acetylcysteine affected both the dynamic viscosities and pipette flow in the two sputa models, with changes in the former parameter having immense effect on the latter. BromAc showed a greater rheological effect on both the sputa models compared to individual agents. Further, correlation was found between the rheological effects and the concentration of agents in the sputa. Hence, this study indicates that BromAc may be used as a successful mucolytic for clearing airway congestion caused by thick mucinous immobile secretion, however further studies with patient sputum samples using aerosol BromAc is warranted.

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Nano-Liposomal Dry Powder Inhaler of Amiloride Hydrochloride

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2006.405 ◽

2006 ◽

Vol 6 (9) ◽

pp. 3001-3009 ◽

Cited By ~ 23

Author(s):

Mahavir Bhupal Chougule ◽

Bijay Kumar Padhi ◽

Ambikanandan Misra

Keyword(s):

Cystic Fibrosis ◽

Drug Release ◽

Phosphate Buffer ◽

Dry Powder Inhaler ◽

Dry Powder ◽

Phosphate Buffer Saline ◽

Amiloride Hydrochloride ◽

Spray Dried

The purpose of this study was to encapsulate Amiloride Hydrochloride into nano-liposomes, incorporate it into dry powder inhaler, and to provide prolonged effective concentration in airways to enhance mucociliary clearance and prevent secondary infection in cystic fibrosis. Liposomes were prepared by thin film hydration technique and then dispersion was passed through high pressure homogenizer to achieve size of nanometer range. Nano-liposomes were separated by centrifugation and were characterized. They were dispersed in phosphate buffer saline pH 7.4 containing carriers (lactose/sucrose/mannitol), and glycine as anti-adherent. The resultant dispersion was spray dried. The spray dried powders were characterized and in vitro drug release studies were performed using phosphate buffer saline pH 7.4. in vitro and in vivo drug pulmonary deposition was carried out using Andersen Cascade Impactor and by estimating drug in bronchial alveolar lavage and lung homogenate after intratracheal instillation in rats respectively. Nano-liposomes were found to have mean volume diameter of 198 ± 15 nm, and 57% ± 1.9% of drug entrapment. Mannitol based formulation was found to have low density, good flowability, particle size of 6.7 ± 0.6 μm determined by Malvern MasterSizer, maximum fine particle fraction of 67.6 ± 0.6%, mean mass aerodynamic diameter 2.3 ± 0.1 μm, and geometric standard deviation 2.4 ± 0.1. Developed formulations were found to have prolonged drug release following Higuchi's Controlled Release model and in vivo studies showed maximal retention time of drug of 12 hrs within the lungs and slow clearance from the lungs. This study provides a practical approach for direct lung delivery of Amiloride Hydrochloride encapsulated in liposomes for controlled and prolonged retention at the site of action from dry powder inhaler. It can provide a promising alternative to the presently available nebulizers in terms of prolonged pharmacological effect, reducing systemic side effects such as potassium retention due to rapid clearance of the drug from lungs in patients suffering from cystic fibrosis.

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Faculty Opinions recommendation of Diagnosis of cystic fibrosis in London and South East England before and after the introduction of newborn screening.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718178886.793506142 ◽

2015 ◽

Author(s):

Uta Griesenbach

Keyword(s):

Cystic Fibrosis ◽

Newborn Screening ◽

Before And After ◽

South East England

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1458. Uncharted territories: applying “precision medicine” to understand the treacherous landscape of extensively and multidrug resistant (XDR and MDR) Pseudomonas aeruginosa in a patient with cystic fibrosis and lung transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1639 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S731-S731

Author(s):

Laura J Rojas ◽

Mohamad Yasmin ◽

Jacquelynn Benjamino ◽

Steven Marshall ◽

Kailynn DeRonde ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Lung Transplantation ◽

Precision Medicine ◽

Clinical Sample ◽

Phylogenetic Reconstruction ◽

Multidrug Resistant ◽

Population Diversity ◽

Before And After ◽

Research Grant

Abstract Background Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with cystic fibrosis (CF). Herein, we describe our experience managing a young woman suffering from CF with XDR P. aeruginosa who underwent lung transplantation. We highlight the contemporary difficulties reconciling the clinical, microbiological, and genetic information. Methods Mechanism-based-susceptibility disk diffusion synergy testing with double and triple antibiotic combinations aided in choosing tailored antimicrobial combinations to control the infection in the pre-transplant period, create an effective perioperative prophylaxis regimen, and manage recurrent infections in the post-transplant period. Thirty-six sequential XDR and PDR P. aeruginosa isolates obtained from the patient within a 17-month period, before and after a double-lung transplant were analyzed by whole genome sequencing (WGS) and RNAseq in order to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence changes over time Results Our phylogenetic reconstruction demonstrates that these isolates represent a genotypically and phenotypically heterogeneous population. The pattern of mutation accumulation and variation of gene expression suggests that a group of closely related strains was present in the patient prior to transplantation and continued to evolve throughout the course of treatment regardless of antibiotic usage.Our findings challenge antimicrobial stewardship programs that assist with the selection and duration of antibiotic regimens in critically ill and immunocompromised patients based on single-isolate laboratory-derived resistant profiles. We propose that an approach sampling the population of pathogens present in a clinical sample instead of single colonies be applied instead when dealing with XDR P. aeruginosa, especially in patients with CF. Conclusion In complex cases such as this, real-time combination testing and genomic/transcriptomic data could lead to the application of true “precision medicine” by helping clinicians choose the combination antimicrobial therapy most likely to be successful against a population of MDR pathogens present. Disclosures Federico Perez, MD, MS, Accelerate (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support) Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support)

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Resting energy expenditure before and after treatment for Pseudomonas aeruginosa infection in patients with cystic fibrosis G DROMMER, AND H VON DER HARDT Medical School, Hannover, Federal Republic of Germany

Nutrition in Clinical Practice ◽

10.1177/088453369400900108 ◽

1994 ◽

Vol 9 (1) ◽

pp. 33-34

Author(s):

W. Frederick Schwenk

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Energy Expenditure ◽

Medical School ◽

Federal Republic ◽

Resting Energy Expenditure ◽

Federal Republic Of Germany ◽

Before And After ◽

Pseudomonas Aeruginosa Infection ◽

Resting Energy

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Possible Crosstalk of the Immune Cells within the Lung and Mediastinal Fat-Associated Lymphoid Clusters in the Acute Inflammatory Lung Asthma-Like Mouse Model

International Journal of Molecular Sciences ◽

10.3390/ijms22136878 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6878

Author(s):

Yaser Hosny Ali Elewa ◽

Mahmoud Mansour Abd Elwakil ◽

Osamu Ichii ◽

Teppei Nakamura ◽

Sherif Kh. A. Mohamed ◽

...

Keyword(s):

Mouse Model ◽

Immune Cells ◽

Phosphate Buffer ◽

Respiratory Diseases ◽

Critical Role ◽

Goblet Cells ◽

Vehicle Group ◽

Natural Helper ◽

B And T Lymphocytes ◽

Intranasal Instillation

Recently, we clarified the function of mediastinal fat-associated lymphoid clusters (MFALCs) in the progression of several respiratory diseases. However, their role has not yet been identified in the lung asthmatic condition. Hence, we compared the immune cells in lung and MFALCs of C57BL/6N mice on days 3 and 7 following intranasal instillation of either papain (papain group “PG”) or phosphate buffer saline (PBS) (vehicle group “VG”). The PG showed significantly prominent MFALCs, numerous goblet cells (GCs), and higher index ratios of different immune cells (macrophages, natural helper cells (NHC), B- and T-lymphocytes) within the MFALCs and lung than in the VG on both days 3 and 7. Interestingly, a tendency of decreased size of MFALCs and a significant reduction in the number of GCs and immune cells were observed within the MFALCs and lung in the PG on day 7 than on day 3. Furthermore, the quantitative parameters of these immune cells in MFALCs were significantly and positively correlated with the size of MFALCs and immune cells in the lung. This suggested that the possible crosstalk between immune cells within MFALCs and the lung could play a critical role in the progression and recovery of the acute inflammatory lung asthma.

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