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Review

Current and novel therapeutic strategies for the management of cystic fibrosis

& ORCID Icon
Pages 535-552 | Received 04 Nov 2020, Accepted 07 Jan 2021, Published online: 22 Jan 2021

References

  • Carapeto AP, Vitorino MV, Santos JD, et al. Mechanical Properties of human bronchial epithelial cells expressing Wt- and mutant CFTR. Int J Mol Sci. 2020;21(8):2916.
  • Martin R, Arden M, Porritt J, et al. Investigating the temporal relationships between symptoms and nebuliser adherence in people with cystic fibrosis: a series of N-of-1 observations. Healthcare 2020;8(1):22.
  • Lababidi N, Ofosu Kissi E, Elgaher WAM, et al. Spray-drying of inhalable, multifunctional formulations for the treatment of biofilms formed in cystic fibrosis. J Control Release. 2019;314:62–71.
  • Jackson AD, Goss CH. Epidemiology of CF: how registries can be used to advance our understanding of the CF population. J Cyst Fibros. 2018;17(3):297–305.
  • Wanyama SS, Thomas M Annual report belgian cystic fibrosis registry [Internet]. Brussels, Belgium; 2016. [cited 2020 Jun 1]. Available from: https://www.muco.be/wp-content/uploads/2019/07/Report-Belgian-CF-registry-2016-EN_final.pdf.
  • Fleischer S, Kraus MS, Gatidis S, et al. New severity assessment in cystic fibrosis: signal intensity and lung volume compared to LCI and FEV1: preliminary results. Eur Radiol. 2020;30(3):1350–1358.
  • Margaroli C, Garratt LW, Horati H, et al. Elastase exocytosis by airway neutrophils is associated with early lung damage in children with cystic fibrosis. Am J Respir Crit Care Med. 2018;199(7):873–881.
  • Trouvé P, Génin E, Férec C. In silico search for modifier genes associated with pancreatic and liver disease in cystic fibrosis. Plos One. 2017;12(3):e0173822.
  • Polverino F, Lu B, Quintero JR, et al. CFTR regulates B cell activation and lymphoid follicle development. Respir Res. 2019;20(1):133.
  • Froux L, Coraux C, Sage E, et al. Short-term consequences of F508del-CFTR thermal instability on CFTR-dependent transepithelial currents in human airway epithelial cells. Sci Rep. 2019;9(1):1–12.
  • Lee D, Hong JH. The fundamental role of bicarbonate transporters and associated carbonic anhydrase enzymes in maintaining ion and pH homeostasis in non-secretory organs. Int J Mol Sci. 2020;21(1):339.
  • Fiore M, Picco C, Moran O. Correctors modify the bicarbonate permeability of F508del-CFTR. Sci Rep. 2020;10(1):1–7.
  • Dobay O, Laub K, Stercz B, et al. Bicarbonate inhibits bacterial growth and biofilm formation of prevalent cystic fibrosis pathogens. Front Microbiol. 2018;9:2245.
  • O’Brien S, Fothergill JL. The role of multispecies social interactions in shaping Pseudomonas aeruginosa pathogenicity in the cystic fibrosis lung. FEMS Microbiol Lett. 2017;364(15):fnx128.
  • Malhotra S, Hayes D, Wozniak DJ. Mucoid Pseudomonas aeruginosa and regional inflammation in the cystic fibrosis lung. J Cyst Fibros. 2019;18(6):796–803.
  • Chen SC-A, Patel S, Meyer W, et al. Pseudomonas aeruginosa inhibits the growth of scedosporium and lomentospora in vitro. Mycopathologia. 2018;183(1):251–261.
  • Cuthbertson L, Walker AW, Oliver AE, et al. Lung function and microbiota diversity in cystic fibrosis. Microbiome. 2020;8(1):1–13.
  • Díez-Aguilar M, Ekkelenkamp M, Morosini M-I, et al. Antimicrobial susceptibility of non-fermenting Gram-negative pathogens isolated from cystic fibrosis patients. Int J Antimicrob Agents. 2019;53(1):84–88.
  • Miró-Cañís S, Capilla-Rubio S, Marzo-Checa L, et al. Multiplex PCR reveals that viruses are more frequent than bacteria in children with cystic fibrosis. J Clin Virol. 2017;86:1–4.
  • Molloy K, Cagney G, Dillon ET, et al. Impaired airway epithelial barrier integrity in response to stenotrophomonas maltophilia proteases, novel insights using cystic fibrosis bronchial epithelial cell secretomics. Front Immunol. 2020;11:198.
  • Pompilio A, Savini V, Fiscarelli E, et al. Clonal diversity, biofilm formation, and antimicrobial resistance among stenotrophomonas maltophilia strains from cystic fibrosis and non-cystic fibrosis patients. Antibiotics. 2020;9(1):15.
  • Tabatabaei M, Dastbarsar M, Moslehi MA. Isolation and identification of pandoraea spp. from bronchoalveolar lavage of cystic fibrosis patients in iran. Ital J Pediatr. 2019;45(1):1–8.
  • Ahmed T, Pattnaik S, Khan MB, et al. Inhibition of quorum sensing–associated virulence factors and biofilm formation in Pseudomonas aeruginosa PAO1 by mycoleptodiscus indicus PUTY1. Braz J Microbiol. 2020;51(2):467–487.
  • Jaques R, Shakeel A, Hoyle C. Novel therapeutic approaches for the management of cystic fibrosis. Multidiscip Respir Med. 2020;15.
  • d’Angelo I, Conte C, La Rotonda MI, et al. Improving the efficacy of inhaled drugs in cystic fibrosis: challenges and emerging drug delivery strategies. Adv Drug Deliv Rev. 2014;75:92–111.
  • Okuda K, Chen G, Subramani DB, et al. Localization of secretory mucins MUC5AC and MUC5B in normal/healthy human airways. Am J Respir Crit Care Med. 2018;199(6):715–727.
  • Rojas DA, Iturra PA, Méndez A, et al. Increase in secreted airway mucins and partial Muc5b STAT6/FoxA2 regulation during pneumocystis primary infection. Sci Rep. 2019;9(1):1–11.
  • Ehre C, Rushton ZL, Wang B, et al. An improved inhaled mucolytic to treat airway muco-obstructive diseases. Am J Respir Crit Care Med. 2018;199(2):171–180.
  • Hill DB, Long RF, Ker WJ, et al. Pathological mucus and impaired mucus clearance in cystic fibrosis patients result from increased concentration, not altered pH. Eur Respir J. 2018;52(6):1801297.
  • Esther CR, Muhlebach MS, Ehre C, et al. Mucus accumulation in the lungs precedes structural changes and infection in children with cystic fibrosis. Sci Transl Med. 2019;11(486):eaav3488.
  • Procianoy E da FA, de Abreu E Silva FA, Maróstica PJC, et al. Chloride conductance, nasal potential difference and cystic fibrosis pathophysiology. Lung. 2020;198(1):151–156.
  • Tester C, Raiff D, Heath T. Impact of clinical, unit-specific guidelines on dornase alfa use in critically Ill pediatric patients without cystic fibrosis. Hosp Pharm. 2020;55(3):199–203.
  • Newsome SJ, Daniel RM, Carr SB, et al. Investigating the effects of long-term dornase alfa use on lung function using registry data. J Cyst Fibros. 2019;18(1):110–117.
  • San Miguel-Pagola M, Reychler G, Cebrià I Iranzo MA, et al. Impact of hypertonic saline nebulisation combined with oscillatory positive expiratory pressure on sputum expectoration and related symptoms in cystic fibrosis: a randomised crossover trial. Physiotherapy. 2020;107:243–251.
  • Luan X, Tam JS, Belev G, et al. Nebulized hypertonic saline triggers nervous system-mediated active liquid secretion in cystic fibrosis swine trachea. Sci Rep. 2019;9(1):1–11.
  • Manoharan A, Das T, Whiteley GS, et al. The effect of N-acetylcysteine in a combined antibiofilm treatment against antibiotic-resistant Staphylococcus aureus. J Antimicrob Chemother. 2020;75(7):1787–1798.
  • Tam J, Nash EF, Ratjen F, et al. Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis. Cochrane Database Syst Rev. 2013.
  • Cristallini C, Barbani N, Ventrelli L, et al. Biodegradable microparticles designed to efficiently reach and act on cystic fibrosis mucus barrier. Mater Sci Eng C. 2019;95:19–28.
  • Xie K, Bunse C, Marcus K, et al. Quantifying changes in the bacterial thiol redox proteome during host-pathogen interaction. Redox Biol. 2019;21:101087.
  • Rimessi A, Pozzato C, Carparelli L, et al. Pharmacological modulation of mitochondrial calcium uniporter controls lung inflammation in cystic fibrosis. Sci Adv. 2020;6(19):eaax9093.
  • Flitter BA, Hvorecny KL, Ono E, et al. Pseudomonas aeruginosa sabotages the generation of host proresolving lipid mediators. PNAS. 2017;114(1):136–141.
  • Forrest OA, Ingersoll SA, Preininger MK, et al. Frontline Science: pathological conditioning of human neutrophils recruited to the airway milieu in cystic fibrosis. J Leukoc Biol. 2018;104(4):665–675.
  • McElvaney OJ, Zaslona Z, Becker-Flegler K, et al. Specific inhibition of the NLRP3 inflammasome as an antiinflammatory strategy in cystic fibrosis. Am J Respir Crit Care Med. 2019;200(11):1381–1391.
  • Dickerhof N, Isles V, Pattemore P, et al. Exposure of Pseudomonas aeruginosa to bactericidal hypochlorous acid during neutrophil phagocytosis is compromised in cystic fibrosis. J Biol Chem. 2019;294(36):13502–13514.
  • Gedik AH, Çakir E, Türkmen AV, et al. Total oxidant and antioxidant status and paraoxonase 1 levels ofchildren with noncystic fibrosis bronchiectasis. Turk J Med Sci. 2020;50(1):1–8.
  • Keir HR, Fong CJ, Crichton ML, et al. Personalised anti-inflammatory therapy for bronchiectasis and cystic fibrosis: selecting patients for controlled trials of neutrophil elastase inhibition. ERJ Open Res. 2019;5(1):00252–02018.
  • Guillon A, Brea D, Luczka E, et al. Inactivation of the interleukin-22 pathway in the airways of cystic fibrosis patients. Cytokine. 2019;113:470–474.
  • Wang X, Gong J, Zhu J, et al. Alpha 1-antitrypsin for treating ventilator-associated lung injury in acute respiratory distress syndrome rats. Exp Lung Res. 2019;45(7):209–219.
  • Schultz D, Surabhi S, Stelling N, et al. 16HBE cell lipid mediator responses to mono and co-infections with respiratory pathogens. Metabolites. 2020;10(3):113.
  • Rosen BH, Evans TIA, Moll SR, et al. Infection is not required for mucoinflammatory lung disease in CFTR-knockout ferrets. Am J Respir Crit Care Med. 2018;197(10):1308–1318.
  • Mogayzel PJ, Naureckas ET, Robinson KA, et al. Cystic fibrosis pulmonary guidelines. Am J Respir Crit Care Med. 2013;187(7):680–689.
  • Tsai C-H, Liao L-Y, Lin C-L, et al. Inhaled corticosteroids and the risks of low-energy fractures in patients with chronic airway diseases: A propensity score matched study. Clin Respir J. 2018;12(5):1830–1837.
  • Pohl K, Nichols DP, Taylor-Cousar JL, et al. Corticosteroid use and increased CXCR2 levels on leukocytes are associated with lumacaftor/ivacaftor discontinuation in cystic fibrosis patients homozygous for the F508del CFTR mutation. Plos One. 2018;13(12):e0209026.
  • Balfour-Lynn IM, Welch K, Smith S. Inhaled corticosteroids for cystic fibrosis. Cochrane Database Syst Rev. 2019;7(7):CD001915.
  • Pascucci C, De Biase RV, Savi D, et al. Deregulation of the growth hormone/insulin-like growth factor-1 axis in adults with cystic fibrosis. J Endocrinol Invest. 2018;41(5):591–596.
  • Konstan MW, VanDevanter DR, Sawicki GS, et al. Association of high-dose ibuprofen use, lung function decline, and long-term survival in children with cystic fibrosis. Ann ATS. 2018;15(4):485–493.
  • Chalmers JD, Boersma W, Lonergan M, et al. Long-term macrolide antibiotics for the treatment of bronchiectasis in adults: an individual participant data meta-analysis. Lancet Respir Med. 2019;7(10):845–854.
  • Huang Z, Wei P, Gan L, et al. Role of erythromycin-regulated histone deacetylase-2 in benign tracheal stenosis. Can Respir J. 2020;2020:e4213807.
  • Kłodzińska SN, Wan F, Jumaa H, et al. Utilizing nanoparticles for improving anti-biofilm effects of azithromycin: a head-to-head comparison of modified hyaluronic acid nanogels and coated poly (lactic-co-glycolic acid) nanoparticles. J Colloid Interface Sci. 2019;555:595–606.
  • Solleti VS, Alhariri M, Halwani M, et al. Antimicrobial properties of liposomal azithromycin for Pseudomonas infections in cystic fibrosis patients. J Antimicrob Chemother. 2015;70(3):784–796.
  • Mejías JC, Forrest OA, Margaroli C, et al. Neutrophil-targeted, protease-activated pulmonary drug delivery blocks airway and systemic inflammation. JCI Insight. 2019;4(23):e131468. .
  • Barth P, Bruijnzeel P, Wach A, et al. Single dose escalation studies with inhaled POL6014, a potent novel selective reversible inhibitor of human neutrophil elastase, in healthy volunteers and subjects with cystic fibrosis. J Cyst Fibros. 2020;19(2):299–304.
  • Santoro A, Ciaglia E, Nicolin V, et al. The isoprenoid end product N6-isopentenyladenosine reduces inflammatory response through the inhibition of the NFκB and STAT3 pathways in cystic fibrosis cells. Inflamm Res. 2018;67(4):315–326.
  • Patrizio G, D’Andria M, D’Abrosca F, et al. Airway clearance with expiratory flow accelerator technology: effectiveness of the “free aspire” device in patients with severe COPD. Turk Thorac J. 2019;20(4):209–215.
  • Wilson LM, Morrison L, Robinson KA. Airway clearance techniques for cystic fibrosis: an overview of cochrane systematic reviews. Cochrane Database Syst Rev. 2019.
  • Donadio MVF, Campos NE, Vendrusculo FM, et al. Respiratory physical therapy techniques recommended for patients with cystic fibrosis treated in specialized centers. Braz J Phys Ther. 2019;(6).
  • Zampogna E, Crisafulli E, D’Andria M, et al. Expiratory Flow Accelerator (EFA) technique on mucus hypersecretion of COPD patients with reduced cough efficiency after a severe exacerbation. Int Clin Med. 2019;3:1–6.
  • Barto TL, Maselli DJ, Daignault S, et al. Real-life experience with high-frequency chest wall oscillation vest therapy in adults with non-cystic fibrosis bronchiectasis. Ther Adv Respir Dis. 2020;14:1753466620932508.
  • Koutsokera A, Varughese RA, Sykes J, et al. Pre-transplant factors associated with mortality after lung transplantation in cystic fibrosis: A systematic review and meta-analysis. J Cyst Fibros. 2019;18(3):407–415.
  • Yeung JC, Machuca TN, Chaparro C, et al. Lung transplantation for cystic fibrosis. J Heart Lung Transplant. 2020;39(6):553–560.
  • Stanzi A, Decaluwe H, Coosemans W, et al. Lobar lung transplantation from deceased donors: a valid option for small-sized patients with cystic fibrosis. Transplant Proc. 2014;46(9):3154–3159.
  • Mendogni P, Palleschi A, Tosi D, et al. Lobar lung transplantation from deceased donor: monocentric experience. Transplant Proc. 2017;49(4):682–685.
  • de Souza Carraro D, Carraro RM, Campos SV, et al. Burkholderia cepacia, cystic fibrosis and outcomes following lung transplantation: experiences from a single center in Brazil. Clinics. 2018;73.
  • Lay C, Law N, Holm AM, et al. Outcomes in cystic fibrosis lung transplant recipients infected with organisms labeled as pan-resistant: an ISHLT Registry‒based analysis. J Heart Lung Transplant. 2019;38(5):545–552.
  • Mainbourg S, Philit F, Touzet S, et al. Cystic fibrosis-related diabetes before lung transplantation is associated with lower survival but does not affect long-term renal function. Pediatr Pulmonol. 2019;54(7):977–983.
  • Zhang T, Price MB, Bravo N, et al. Combined lung-liver and delayed kidney transplantation for cystic fibrosis clinical approach and outcome: a case report. Transplant Proc. 2020;(9).
  • Barbas AS, Dib MJ, Al-Adra DP, et al. Combined lung-liver-pancreas transplantation in a recipient with cystic fibrosis. J Cyst Fibros. 2018;17(1):e1–e4.
  • Bandsma RHJ, Bozic MA, Fridell JA, et al. Simultaneous liver–pancreas transplantation for cystic fibrosis-related liver disease: a multicenter experience. J Cyst Fibros. 2014;13(4):471–477.
  • Schwensen HF, Moser C, Perch M, et al. Pseudomonas aeruginosa antibody response in cystic fibrosis decreases rapidly following lung transplantation. J Cyst Fibros. 2020;19(4):587–594.
  • Aygun F, Aygun FD, Varol F, et al. Can nebulised colistin therapy improve outcomes in critically Ill children with multi-drug resistant gram-negative bacterial pneumonia? Antibiotics. 2019;8(2):40.
  • Cayli YA, Sahin S, Buttini F, et al. Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a mucolytic agent for cystic fibrosis patients. Drug Dev Ind Pharm. 2017;43(8):1378–1389.
  • Clancy JP, Dupont L, Konstan MW, et al. Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. Thorax. 2013;68(9):818–825.
  • Heirali AA, Workentine ML, Acosta N, et al. The effects of inhaled aztreonam on the cystic fibrosis lung microbiome. Microbiome. 2017;5(1):1–14.
  • Stormbroek BV, Zampoli M, Morrow BM. Nebulized gentamicin in combination with systemic antibiotics for eradicating early Pseudomonas aeruginosa infection in children with cystic fibrosis. Pediatr Pulmonol. 2019;54(4):393–398.
  • Bassetti M, Castaldo N, Cattelan A, et al. Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience. Int J Antimicrob Agents. 2019;53(4):408–415.
  • Kordes A, Preusse M, Willger SD, et al. Genetically diverse Pseudomonas aeruginosa populations display similar transcriptomic profiles in a cystic fibrosis explanted lung. Nat Commun. 2019;10(1):1–10.
  • Rampioni G, Pillai CR, Longo F, et al. Effect of efflux pump inhibition on Pseudomonas aeruginosa transcriptome and virulence. Sci Rep. 2017;7(1):1–14.
  • Armijo LM, Wawrzyniec SJ, Kopciuch M, et al. Antibacterial activity of iron oxide, iron nitride, and tobramycin conjugated nanoparticles against Pseudomonas aeruginosa biofilms. J Nanobiotechnol. 2020;18:1–27.
  • Harrington NE, Sweeney E, Harrison F. Building a better biofilm - Formation of in vivo-like biofilm structures by Pseudomonas aeruginosa in a porcine model of cystic fibrosis lung infection. Biofilm. 2020;2:100024.
  • Parasuraman P, Devadatha B, Sarma VV, et al. Anti-quorum sensing and antibiofilm activities of Blastobotrys parvus PPR3 against Pseudomonas aeruginosa PAO1. Microb Pathog. 2020;138:103811.
  • Law N, Logan C, Yung G, et al. Successful adjunctive use of bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa infection in a cystic fibrosis patient. Infection. 2019;47(4):665–668. .
  • Fong SA, Drilling A, Morales S, et al. Activity of bacteriophages in removing biofilms of pseudomonas aeruginosa isolates from chronic rhinosinusitis patients. Front Cell Infect Microbiol. 2017;7:418.
  • Lamers RP, Cavallari JF, Burrows LL. The efflux inhibitor phenylalanine-arginine beta-naphthylamide (PAβN) permeabilizes the outer membrane of gram-negative bacteria. Plos One. 2013;8(3):e60666.
  • Porsio B, Craparo EF, Mauro N, et al. Mucus and cell-penetrating nanoparticles embedded in nano into micro formulations for pulmonary delivery of ivacaftor in patients with cystic fibrosis. ACS Appl Mater Interfaces. 2018;10(1):165–181. .
  • Casciaro B, d’Angelo I, Zhang X, et al. Poly(lactide-co-glycolide) nanoparticles for prolonged therapeutic efficacy of esculentin-1a-derived antimicrobial peptides against pseudomonas aeruginosa lung infection: in vitro and in vivo studies. Biomacromolecules. 2019;20(5):1876–1888.
  • Mhule D, Kalhapure RS, Jadhav M, et al. Synthesis of an oleic acid based pH-responsive lipid and its application in nanodelivery of vancomycin. Int J Pharm. 2018;550(1–2):149–159.
  • Farhangi M, Kobarfard F, Mahboubi A, et al. Preparation of an optimized ciprofloxacin-loaded chitosan nanomicelle with enhanced antibacterial activity. Drug Dev Ind Pharm. 2018;44(8):1273–1284.
  • Gao M, Long X, Du J, et al. Enhanced curcumin solubility and antibacterial activity by encapsulation in PLGA oily core nanocapsules. Food Funct. 2020;11(1):448–455.
  • El-Say KM, El-Sawy HS. Polymeric nanoparticles: promising platform for drug delivery. Int J Pharm. 2017;528(1–2):675–691.
  • Muslim SN, Kadmy IMSA, Ali ANM, et al. Chitosan extracted from Aspergillus flavus shows synergistic effect, eases quorum sensing mediated virulence factors and biofilm against nosocomial pathogen Pseudomonas aeruginosa. Int J Biol Macromol. 2018;107:52–58.
  • Badawy MSEM, Riad OKM, Taher FA, et al. Chitosan and chitosan-zinc oxide nanocomposite inhibit expression of LasI and RhlI genes and quorum sensing dependent virulence factors of Pseudomonas aeruginosa. Int J Biol Macromol. 2020;149:1109–1117.
  • Muñoz-Escobar A, Reyes-López SY. Antifungal susceptibility of Candida species to copper oxide nanoparticles on polycaprolactone fibers (PCL-CuONPs). Plos One. 2020;15:e0228864.
  • Fatima S, Iqbal Z, Panda AK, et al. Polymeric nanoparticles as a platform for permeability enhancement of class III drug amikacin. Colloids Surf B Biointerfaces. 2018;169:206–213.
  • Ernst J, Klinger-Strobel M, Arnold K, et al. Polyester-based particles to overcome the obstacles of mucus and biofilms in the lung for tobramycin application under static and dynamic fluidic conditions. Eur J Pharm Biopharm. 2018;131:120–129.
  • Gupta A, Landis RF, Li C-H, et al. Engineered polymer nanoparticles with unprecedented antimicrobial efficacy and therapeutic indices against multidrug-resistant bacteria and biofilms. J Am Chem Soc. 2018;140(38):12137–12143.
  • Li J, Zhang K, Ruan L, et al. Block copolymer nanoparticles remove biofilms of drug-resistant gram-positive bacteria by nanoscale bacterial debridement. Nano Lett. 2018;18(7):4180–4187.
  • Sangave PC, Matkar NM, Suvarna V. Antimicrobial activity of metallic nanoparticles using prokaryotic model organisms. In: Siddhardha B, Dyavaiah M, Kasinathan K, editors. Model organisms to study biological activities and toxicity of nanoparticles. Singapore: Springer; 2020. p. 59–81.
  • Tasia W, Lei C, Cao Y, et al. Enhanced eradication of bacterial biofilms with DNase I-loaded silver-doped mesoporous silica nanoparticles. Nanoscale. 2020;12(4):2328–2332.
  • Wan B, Zhu Y, Tao J, et al. Alginate lyase guided silver nanocomposites for eradicating pseudomonas aeruginosa from lungs. ACS Appl Mater Interfaces. 2020;12(8):9050–9061.
  • Liao C, Li Y, Tjong SC. Bactericidal and cytotoxic properties of silver nanoparticles. Int J Mol Sci. 2019;20(2):449.
  • Jadhav M, Kalhapure RS, Rambharose S, et al. Novel lipids with three C18-fatty acid chains and an amino acid head group for pH-responsive and sustained antibiotic delivery. Chem Phys Lipids. 2018;212:12–25.
  • Alhariri M, Omri A. Efficacy of liposomal bismuth-ethanedithiol-loaded tobramycin after intratracheal administration in rats with pulmonary pseudomonas aeruginosa infection. Antimicrob Agents Chemother. 2013;57(1):569–578.
  • Ghodake V, Vishwakarma J, Vavilala SL, et al. Cefoperazone sodium liposomal formulation to mitigate P. aeruginosa biofilm in Cystic fibrosis infection: A QbD approach. Int J Pharm. 2020;587:119696.
  • Zhang J, Leifer F, Rose S, et al. Amikacin liposome inhalation suspension (ALIS) penetrates non-tuberculous mycobacterial biofilms and enhances amikacin uptake into macrophages. Front Microbiol. 2018;9:915.
  • Cipolla D, Blanchard J, Gonda I. Development of liposomal ciprofloxacin to treat lung infections. Pharmaceutics. 2016;8(1):6.
  • Ye T, Sun S, Sugianto TD, et al. Novel combination proliposomes containing tobramycin and clarithromycin effective against Pseudomonas aeruginosa biofilms. Int J Pharm. 2018;552(1–2):130–138. .
  • Obuobi S, Julin K, Fredheim EGA, et al. Liposomal delivery of antibiotic loaded nucleic acid nanogels with enhanced drug loading and synergistic anti-inflammatory activity against S. aureus intracellular infections. J Control Release. 2020;324:620–632.
  • Dave V, Gupta A, Singh P, et al. Synthesis and characterization of celecoxib loaded PEGylated liposome nanoparticles for biomedical applications. Nano-Struct Nano-Objects. 2019;18:100288.
  • Refaat H, Naguib YW, Elsayed MMA, et al. Modified spraying technique and response surface methodology for the preparation and optimization of propolis liposomes of enhanced anti-proliferative activity against human melanoma cell line A375. Pharmaceutics. 2019;11(11):558.
  • Yingyuad P, Sinthuvanich C, Leepasert T, et al. Preparation, characterization and in vitro evaluation of calothrixin B liposomes. J Drug Deliv Sci Technol. 2018;44:491–497.
  • Li X, Chen D, Le C, et al. Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake. Int J Nanomedicine. 2011;6:3151–3162.
  • Patil YP, Jadhav S. Novel methods for liposome preparation. Chem Phys Lipids. 2014;177:8–18.
  • Osman NM, Sexton DW, Saleem IY. Toxicological assessment of nanoparticle interactions with the pulmonary system. Nanotoxicology. 2020;14(1):21–58.
  • Hilpert K, Elliott MR, Volkmer-Engert R, et al. Sequence requirements and an optimization strategy for short antimicrobial peptides. Chem Biol. 2006;13(10):1101–1107.
  • Judzewitsch PR, Corrigan N, Trujillo F, et al. High-throughput process for the discovery of antimicrobial polymers and their upscaled production via flow polymerization. Macromolecules. 2020;53(2):631–639.
  • Garbacz K, Kamysz W, Piechowicz L. Activity of antimicrobial peptides, alone or combined with conventional antibiotics, against Staphylococcus aureus isolated from the airways of cystic fibrosis patients. Virulence. 2017;8(1):94–100.
  • Geitani R, Moubareck CA, Xu Z, et al. Expression and roles of antimicrobial peptides in innate defense of airway mucosa: potential implication in cystic fibrosis. Front Immunol. 2020;11:1198.
  • Geitani R, Ayoub Moubareck C, Touqui L, et al. Cationic antimicrobial peptides: alternatives and/or adjuvants to antibiotics active against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa. BMC Microbiol. 2019;19(1):54.
  • Oliveira JTA, Souza PFN, Vasconcelos IM, et al. Mo-CBP3-PepI, Mo-CBP3-PepII, and Mo-CBP3-PepIII are synthetic antimicrobial peptides active against human pathogens by stimulating ROS generation and increasing plasma membrane permeability. Biochimie. 2019;157:10–21.
  • Awatade NT, Ramalho S, Silva IAL, et al. R560S: A class II CFTR mutation that is not rescued by current modulators. J Cyst Fibros. 2019;18(2):182–189.
  • Volkova N, Moy K, Evans J, et al. Disease progression in patients with cystic fibrosis treated with ivacaftor: data from national US and UK registries. J Cyst Fibros. 2020;19(1):68–79.
  • Misgault B, Chatron E, Reynaud Q, et al. Effect of one-year lumacaftor–ivacaftor treatment on glucose tolerance abnormalities in cystic fibrosis patients. J Cyst Fibros. 2020;19(5):712–716.
  • Nichols AL, Davies JC, Jones D, et al. Restoration of exocrine pancreatic function in older children with cystic fibrosis on ivacaftor. Paediatr Respir Rev. 2020;35:99–102.
  • Nash EF, Middleton PG, Taylor-Cousar JL. Outcomes of pregnancy in women with cystic fibrosis (CF) taking CFTR modulators – an international survey. J Cyst Fibros. 2020;19(4):521–526.
  • Nick JA, St. Clair C, Jones MC, et al. Ivacaftor in cystic fibrosis with residual function: lung function results from an N-of-1 study. J Cyst Fibros. 2020;19(1):91–98.
  • Gees M, Musch S, Van der Plas S, et al. Identification and characterization of novel CFTR potentiators. Front Pharmacol. 2018;9:1221.
  • Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011;365(18):1663–1672.
  • Veit G, Da Fonte DF, Avramescu RG, et al. Mutation-specific dual potentiators maximize rescue of CFTR gating mutants. J Cyst Fibros. 2020;19(2):236–244.
  • Davies JC, Moskowitz SM, Brown C, et al. VX-659–tezacaftor–ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles. N Engl J Med. 2018;379(17):1599–1611.
  • Wainwright CE, Elborn JS, Ramsey BW, et al. Lumacaftor–ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med. 2015;373(3):220–231.
  • Munck A, Kerem E, Ellemunter H, et al. Tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for minimal function CFTR mutations. J Cyst Fibros. 2020;19(6):962–968.
  • Vertex Pharmaceuticals Incorporated. FDA approves TRIKAFTATM (elexacaftor/tezacaftor/ivacaftor and ivacaftor) to treat the underlying cause of cystic fibrosis in people ages 12 and older who have at least one F508del mutation | vertex pharmaceuticals [Internet]. [cited 2020 Sep 21]. Available from: https://investors.vrtx.com/news-releases/news-release-details/fda-approves-trikafta-elexacaftortezacaftorivacaftor-and.
  • Taylor-Cousar JL, Munck A, McKone EF, et al. Tezacaftor–ivacaftor in patients with cystic fibrosis homozygous for Phe508del. N Engl J Med. 2017;377(21):2013–2023.
  • Middleton PG, Mall MA, Dřevínek P, et al. Elexacaftor–tezacaftor–ivacaftor for cystic fibrosis with a single Phe508del allele. N Engl J Med. 2019;381(19):1809–1819.
  • Keating D, Marigowda G, Burr L, et al. VX-445–tezacaftor–ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles. N Engl J Med. 2018;379(17):1612–1620.
  • Dukovski D, Villella A, Bastos C, et al. Amplifiers co-translationally enhance CFTR biosynthesis via PCBP1-mediated regulation of CFTR mRNA. J Cyst Fibros. 2020;19(5):733–741. .
  • Giuliano KA, Wachi S, Drew L, et al. Use of a high-throughput phenotypic screening strategy to identify amplifiers, a novel pharmacological class of small molecules that exhibit functional synergy with potentiators and correctors. SLAS Discovery. 2018;23(2):111–121.
  • Pranke I, Bidou L, Martin N, et al. Factors influencing readthrough therapy for frequent cystic fibrosis premature termination codons. ERJ Open Res. 2018;4(1):00080–02017.
  • PTC Therapeutics. An open-label safety and efficacy study for patients with nonsense mutation cystic fibrosis previously treated with ataluren (PTC124) [Internet]. clinicaltrials.gov; 2020 [cited 2020 Sep 18]. Report No.: NCT02107859. Available from: https://clinicaltrials.gov/ct2/show/NCT02107859.
  • Wilschanski M, Yahav Y, Yaacov Y, et al. Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR Stop mutations. N Engl J Med. 2003;349(15):1433–1441.
  • Xue X, Mutyam V, Tang L, et al. Synthetic aminoglycosides efficiently suppress cystic fibrosis transmembrane conductance regulator nonsense mutations and are enhanced by ivacaftor. Am J Respir Cell Mol Biol. 2013;50(4):805–816.
  • Schneider EK, Azad MAK, Han M-L, et al. An “unlikely” pair: the antimicrobial synergy of polymyxin b in combination with the cystic fibrosis transmembrane conductance regulator drugs KALYDECO and ORKAMBI. ACS Infect Dis. 2016;2(7):478–488.
  • Stallings VA, Sainath N, Oberle M, et al. Energy balance and mechanisms of weight gain with ivacaftor treatment of cystic fibrosis gating mutations. J Pediatr. 2018;201:229–237.e4.
  • Trimble AT, Donaldson SH. Ivacaftor withdrawal syndrome in cystic fibrosis patients with the G551D mutation. J Cyst Fibros. 2018;17(2):e13–e16.
  • Guimbellot JS, Acosta EP, Rowe SM. Sensitivity of ivacaftor to drug-drug interactions with rifampin, a cytochrome P450 3A4 inducer. Pediatr Pulmonol. 2018;53(5):E6–E8.
  • Thomas KA Drug costs $272,000 a year. not so fast, says New York State. The New York Times [Internet]. 2018 Jun 24 [cited 2020 Sep 21]. Available from: https://www.nytimes.com/2018/06/24/health/drug-prices-orkambi-new-york.html.
  • Cystic Fibrosis Canada. Trikafta [Internet]. Cystic Fibrosis Canada. [cited 2020 Sep 21]. Available from: https://www.cysticfibrosis.ca/.
  • Pereira SV-N, Ribeiro JD, Ribeiro AF, et al. Novel, rare and common pathogenic variants in the CFTR gene screened by high-throughput sequencing technology and predicted by in silico tools. Sci Rep. 2019;9(1):6234.
  • Carlon MS, Vidović D, Birket S. Roadmap for an early gene therapy for cystic fibrosis airway disease. Prenat Diagn. 2017;37(12):1181–1190.
  • Griesenbach U, Alton EWFW. Moving forward: cystic fibrosis gene therapy. Hum Mol Genet. 2013;22(R1):R52–R58.
  • Velino C, Carella F, Adamiano A, et al. Nanomedicine approaches for the pulmonary treatment of cystic fibrosis. Front Bioeng Biotechnol. 2019;7:406.
  • Alton EWFW, Beekman JM, Boyd AC, et al. Preparation for a first-in-man lentivirus trial in patients with cystic fibrosis. Thorax. 2017;72(2):137–147.
  • Sainz-Ramos M, Villate-Beitia I, Gallego I, et al. Non-viral mediated gene therapy in human cystic fibrosis airway epithelial cells recovers chloride channel functionality. Int J Pharm. 2020;588:119757.
  • Alton EWFW, Armstrong DK, Ashby D, et al. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med. 2015;3(9):684–691. .
  • Haque AKMA, Dewerth A, Antony JS, et al. Chemically modified h CFTR mRNAs recuperate lung function in a mouse model of cystic fibrosis. Sci Rep. 2018;8(1):16776.
  • Robinson E, MacDonald KD, Slaughter K, et al. Lipid nanoparticle-delivered chemically modified mRNA restores chloride secretion in cystic fibrosis. Mol Ther. 2018;26(8):2034–2046.
  • Translate Bio, Inc. A phase 1/2, randomized, double-blinded, placebo-controlled, combined single and multiple ascending dose study evaluating the safety, tolerability, and biological activity of MRT5005 administered by nebulization to adult subjects with cystic fibrosis [Internet]. clinicaltrials.gov; 2020 [cited 2020 Dec 23]. Report No.: NCT03375047. Available from: https://clinicaltrials.gov/ct2/show/NCT03375047.
  • Maule G, Casini A, Montagna C, et al. Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing. Nat Commun. 2019;10(1):1–11.
  • Erwood S, Laselva O, Bily TMI, et al. Allele-specific prevention of nonsense-mediated decay in cystic fibrosis using homology-independent genome editing. Mol Ther Methods Clin Dev. 2020;17:1118–1128.
  • Barba AA, Bochicchio S, Dalmoro A, et al. Lipid delivery systems for nucleic-acid-based-drugs: from production to clinical applications. Pharmaceutics. 2019;11(8):360.
  • Kazemabadi FZ, Heydarinasab A, Akbarzadeh A, et al. Preparation, characterization and in vitro evaluation of PEGylated nanoliposomal containing etoposide on lung cancer. Artif Cells Nanomed Biotechnol. 2019;47(1):3222–3230.
  • Reuter M, Kruger DH. Approaches to optimize therapeutic bacteriophage and bacteriophage-derived products to combat bacterial infections. Virus Genes. 2020;56(2):136–149.
  • Dickerhof N, Huang J, Min E, et al. Myeloperoxidase inhibition decreases morbidity and oxidative stress in mice with cystic fibrosis-like lung inflammation. Free Radic Biol Med. 2020;152:91–99.
  • Wu Q, Chong L, Shao Y, et al. Lipoxin A4 reduces hyperoxia-induced lung injury in neonatal rats through PINK1 signaling pathway. Int Immunopharmacol. 2019;73:414–423.
  • Higgins G, Fustero Torre C, Tyrrell J, et al. Lipoxin A4 prevents tight junction disruption and delays the colonization of cystic fibrosis bronchial epithelial cells by Pseudomonas aeruginosa. Am J Physiol Lung Cell Mol. 2016;310(11):L1053–L1061.
  • Higgins G, Buchanan P, Perriere M, et al. Activation of P2RY11 and ATP release by lipoxin A4 restores the airway surface liquid layer and epithelial repair in cystic fibrosis. Am J Respir Cell Mol Biol. 2014;51(2):178–190.
  • Buchanan PJ, McNally P, Harvey BJ, et al. Lipoxin A4-mediated KATP potassium channel activation results in cystic fibrosis airway epithelial repair. Am J Physiol Lung Cell Mol. 2013;305(2):L193–L201.
  • Kummarapurugu AB, Afosah DK, Sankaranarayanan NV, et al. Molecular principles for heparin oligosaccharide–based inhibition of neutrophil elastase in cystic fibrosis. J Biol Chem. 2018;293(32):12480–12490.

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