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Preface| Volume 43, ISSUE 4, Pxiii-xvi, December 2022

Cystic Fibrosis in the Era of Highly Effective CFTR Modulators

DOI:https://doi.org/10.1016/j.ccm.2022.07.003
Cystic Fibrosis in the Era of Highly Effective CFTR Modulators
Previous ArticleForthcoming Issues
Next ArticleToward a Broader Understanding of Cystic Fibrosis Epidemiology and Its Impact on Clinical Manifestations
      Figure thumbnail fx1
      Clemente J. Britto, MD, ATSF, Editor
      Figure thumbnail fx2
      Jennifer L. Taylor-Cousar, MD, MSCS, ATSF, Editor
      Cystic fibrosis (CF) was described as a clinical entity more than eighty years ago.
      • Riordan J.R.
      • Rommens J.M.
      • Kerem B.
      • et al.
      Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
      Science. 1989; 245: 1066-1073
      , 
      • Davis P.B.
      Cystic fibrosis since 1938.
      Am J Respir Crit Care Med. 2006; 173: 475-482
      , 
      • Andersen D.H.
      Cystic fibrosis of the pancreas and its relation to celiac disease: a clinical and pathologic study.
      Am J Dis Child. 1938; 56: 344-399
      With the development of comprehensive care centers and therapies directed at the signs and symptoms of the disease, survival improved.
      Patient Registry. Cystic Fibrosis Foundation.
      https://www.cff.org/medical-professionals/patient-registry
      What once was a disease only of children has become a chronic disease of adults for whom the median predicted survival is fifty years of age.
      • McKone E.F.
      • Ariti C.
      • Jackson A.
      • et al.
      Survival estimates in European cystic fibrosis patients and the impact of socioeconomic factors: a retrospective registry cohort study.
      Eur Respir J. 2021; 58https://doi.org/10.1183/13993003.02288-2020
      ,
      • Stephenson A.L.
      • Sykes J.
      • Stanojevic S.
      • et al.
      Survival Comparison of Patients With Cystic Fibrosis in Canada and the United States: A Population-Based Cohort Study.
      Ann Intern Med. 2017; 166: 537-546
      As the natural history of CF has evolved, so has the recognition of previously underdiagnosed populations of people with CF, contributing to its rising prevalence around the world.
      • Hamosh A.
      • FitzSimmons S.C.
      • Macek Jr., M.
      • et al.
      Comparison of the clinical manifestations of cystic fibrosis in black and white patients.
      J Pediatr. 1998; 132: 255-259
      , 
      • Powers C.A.
      • Potter E.M.
      • Wessel H.U.
      • et al.
      Cystic fibrosis in Asian Indians.
      Arch Pediatr Adolesc Med. 1996; 150: 554-555
      , 
      • Yamashiro Y.
      • Shimizu T.
      • Oguchi S.
      • et al.
      The estimated incidence of cystic fibrosis in Japan.
      J Pediatr Gastroenterol Nutr. 1997; 24: 544-547
      , 
      • Stafler P.
      • Mei-Zahav M.
      • Wilschanski M.
      • et al.
      The impact of a national population carrier screening program on cystic fibrosis birth rate and age at diagnosis: Implications for newborn screening.
      J Cyst Fibros. 2016; 15: 460-466
      We are in the midst of a new era in CF care ushered in by the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, small molecules that significantly restore CFTR protein function. People with CF are experiencing marked rapid and sustained improvements in lung function, nutritional state, and quality of life.
      • Ramsey B.W.
      • Davies J.
      • McElvaney N.G.
      • et al.
      A CFTR potentiator in patients with cystic fibrosis and the G551D mutation.
      N Engl J Med. 2011; 365: 1663-1672
      , 
      • Taylor-Cousar J.L.
      • Munck A.
      • McKone E.F.
      • et al.
      Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del.
      N Engl J Med. 2017; 377: 2013-2023
      , 
      • Middleton P.G.
      • Mall M.A.
      • Dřevínek P.
      • et al.
      Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele.
      N Engl J Med. 2019; 381: 1809-1819
      With the approval of the first triple-modulator combination, elexacaftor/tezacaftor/ivacaftor, for people with CF with at least one copy of the most common CF mutations in those of European ancestry, Phe508del (F508del), approximately 90% of the CF population is now eligible for highly effective modulator therapy (HEMT) and its associated transformational health benefits.
      • Middleton P.G.
      • Mall M.A.
      • Dřevínek P.
      • et al.
      Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele.
      N Engl J Med. 2019; 381: 1809-1819
      Since the previous CF-focused issue of Clinics in Chest Medicine,
      • Koff J.
      Cystic Fibrosis, an Issue of Clinics in chest medicine.
      Elsevier Health Sciences, 2016
      there have been broad advances in our understanding of the immunopathogenesis of CF and the remarkable impact of modulators on immune cell function, inflammation, and repair mechanisms.
      • Gillan J.L.
      • Davidson D.J.
      • Gray R.D.
      Targeting cystic fibrosis inflammation in the age of CFTR modulators: focus on macrophages.
      Eur Respir J. 2021; 57https://doi.org/10.1183/13993003.03502-2020
      , 
      • Hisert K.B.
      • Birkland T.P.
      • Schoenfelt K.Q.
      • et al.
      Ivacaftor decreases monocyte sensitivity to interferon-γ in people with cystic fibrosis.
      ERJ Open Res. 2020; 6https://doi.org/10.1183/23120541.00318-2019
      , 
      • Jarosz-Griffiths H.H.
      • Scambler T.
      • Wong C.H.
      • et al.
      Different CFTR modulator combinations downregulate inflammation differently in cystic fibrosis.
      Elife. 2020; 9https://doi.org/10.7554/eLife.54556
      Indeed, the CFTR correction afforded by HEMT is increasingly recognized as a modifying factor in the microbiome and airway inflammatory response of people with CF.
      • Harris J.K.
      • Wagner B.D.
      • Zemanick E.T.
      • et al.
      Changes in Airway Microbiome and Inflammation with Ivacaftor Treatment in Patients with Cystic Fibrosis and the G551D Mutation.
      Ann Am Thorac Soc. 2020; 17: 212-220
      , 
      • Grasemann H.
      • Gonska T.
      • Avolio J.
      • et al.
      Effect of ivacaftor therapy on exhaled nitric oxide in patients with cystic fibrosis.
      J Cyst Fibros. 2015; 14: 727-732
      , 
      • Green M.
      • Lindgren N.
      • Henderson A.
      • et al.
      Ivacaftor partially corrects airway inflammation in a humanized G551D rat.
      Am J Physiol Lung Cell Mol Physiol. 2021; 320: L1093-L1100
      , 
      • Barnaby R.
      • Koeppen K.
      • Nymon A.
      • et al.
      Lumacaftor (VX-809) restores the ability of CF macrophages to phagocytose and kill Pseudomonas aeruginosa.
      Am J Physiol Lung Cell Mol Physiol. 2018; 314: L432-L438
      , 
      • Ruffin M.
      • Roussel L.
      • Maillé É.
      • et al.
      Vx-809/Vx-770 treatment reduces inflammatory response to Pseudomonas aeruginosa in primary differentiated cystic fibrosis bronchial epithelial cells.
      Am J Physiol Lung Cell Mol Physiol. 2018; 314: L635-L641
      Advances have also emerged in animal models, cell-based assays, and approaches to measure and titrate functional responses to modulators in human tissues and cells.
      • Clancy J.P.
      • Cotton C.U.
      • Donaldson S.H.
      • et al.
      CFTR modulator theratyping: Current status, gaps and future directions.
      J Cyst Fibros. 2019; 18: 22-34
      , 
      • Pedemonte N.
      • Zegarra-Moran O.
      • Galietta L.J.V.
      High-throughput screening of libraries of compounds to identify CFTR modulators.
      Methods Mol Biol. 2011; 741: 13-21
      , 
      • Sui J.
      • Cotard S.
      • Andersen J.
      • et al.
      Optimization of a Yellow fluorescent protein-based iodide influx high-throughput screening assay for cystic fibrosis transmembrane conductance regulator (CFTR) modulators.
      Assay Drug Dev Technol. 2010; 8: 656-668
      , 
      • Liang F.
      • Shang H.
      • Jordan N.J.
      • et al.
      High-Throughput Screening for Readthrough Modulators of CFTR PTC Mutations.
      SLAS Technol. 2017; 22: 315-324
      Emerging tools, such as novel pulmonary function measures, pulmonary imaging, patient-reported outcomes, and new molecular biomarkers, will become increasingly important in understanding CF pathogenesis and treatment response.
      • Horsley A.R.
      • Belcher J.
      • Bayfield K.
      • et al.
      Longitudinal assessment of lung clearance index to monitor disease progression in children and adults with cystic fibrosis.
      Thorax. 2021; https://doi.org/10.1136/thoraxjnl-2021-216928
      , 
      • Smith L.
      • Aldag I.
      • Hughes P.
      • et al.
      Longitudinal monitoring of disease progression in children with mild CF using hyperpolarised gas MRI and LCI.
      Eur Respir J. 2016; 48https://doi.org/10.1183/13993003.congress-2016.OA284
      , 
      • Szczesniak R.
      • Turkovic L.
      • Andrinopoulou E.R.
      • et al.
      Chest imaging in cystic fibrosis studies: What counts, and can be counted?.
      J Cyst Fibros. 2017; 16: 175-185
      , 
      • Dournes G.
      • Walkup L.L.
      • Benlala I.
      • et al.
      The Clinical Use of Lung MRI in Cystic Fibrosis: What, Now, How?.
      Chest. 2021; 159: 2205-2217
      , 
      • Beswick D.M.
      • Humphries S.M.
      • Balkissoon C.D.
      • et al.
      Impact of CFTR Therapy on Chronic Rhinosinusitis and Health Status: Deep Learning CT Analysis and Patient Reported Outcomes.
      Ann Am Thorac Soc. 2021; https://doi.org/10.1513/AnnalsATS.202101-057OC
      , 
      • Sathe M.
      • Moshiree B.
      • Vu P.T.
      • et al.
      Utilization of electronic patient-reported outcome measures in cystic fibrosis research: Application to the GALAXY study.
      J Cyst Fibros. 2021; 20: 605-611
      , 
      • Ishak A.
      • Stick S.M.
      • Turkovic L.
      • et al.
      BAL Inflammatory Markers Can Predict Pulmonary Exacerbations in Children With Cystic Fibrosis.
      Chest. 2020; 158: 2314-2322
      , 
      • Khanal S.
      • Webster M.
      • Niu N.
      • et al.
      SPLUNC1: a novel marker of cystic fibrosis exacerbations.
      Eur Respir J. 2021; https://doi.org/10.1183/13993003.00507-2020
      Apart from the well-documented impact of HEMT on lung function and nutritional outcomes, HEMT promises to have extensive effects in multiple areas of clinical care. Emerging reports of effects range from changes in airway microbial communities with associated opportunities for developing novel antimicrobial therapies, evolving knowledge regarding the surveillance and management of long-term endocrine and gastrointestinal complications, and new opportunities in family planning and reproductive health.
      • Payne J.E.
      • Dubois A.V.
      • Ingram R.J.
      • et al.
      Activity of innate antimicrobial peptides and ivacaftor against clinical cystic fibrosis respiratory pathogens.
      Int J Antimicrob Agents. 2017; 50: 427-435
      , 
      • 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: 68-79
      , 
      • Shteinberg M.
      • Taylor-Cousar J.L.
      • Durieu I.
      • et al.
      Fertility and Pregnancy in Cystic Fibrosis.
      Chest. 2021; https://doi.org/10.1016/j.chest.2021.07.024
      , 
      • Freeman A.J.
      • Sathe M.
      • Aliaj E.
      • et al.
      Designing the GALAXY study: Partnering with the cystic fibrosis community to optimize assessment of gastrointestinal symptoms.
      J Cyst Fibros. 2021; 20: 598-604
      , 
      • Smith S.
      • Rowbotham N.J.
      • Regan K.H.
      Inhaled anti-pseudomonal antibiotics for long-term therapy in cystic fibrosis.
      Cochrane Database Syst Rev. 2018; 3: CD001021
      , 
      • Abdalla M.Y.
      • Switzer B.L.
      • Goss C.H.
      • et al.
      Gallium Compounds Exhibit Potential as New Therapeutic Agents against Mycobacterium abscessus.
      Antimicrob Agents Chemother. 2015; 59: 4826-4834
      , 
      • Chan B.K.
      • Stanley G.
      • Modak M.
      • et al.
      Bacteriophage therapy for infections in CF.
      Pediatr Pulmonol. 2021; 56: S4-S9
      HEMT has had a transformative effect on the lives of many people with CF. However, some questions remain to be answered. For example, there are ongoing efforts to develop safe and effective readthrough agents and the next generation of modulators and immunomodulatory drugs for those ineligible for or intolerant of currently approved HEMT. Ultimately, gene replacement or editing will be necessary to cure CF.
      • Christopher Boyd A.
      • Guo S.
      • Huang L.
      • et al.
      New approaches to genetic therapies for cystic fibrosis.
      J Cyst Fibros. 2020; 19: S54-S59
      , 
      • Pranke I.
      • Golec A.
      • Hinzpeter A.
      • et al.
      Emerging Therapeutic Approaches for Cystic Fibrosis. From Gene Editing to Personalized Medicine.
      Front Pharmacol. 2019; 10: 121
      , 
      • Lueck J.D.
      • Yoon J.S.
      • Perales-Puchalt A.
      • et al.
      Engineered transfer RNAs for suppression of premature termination codons.
      Nat Commun. 2019; 10: 822
      , 
      • Crane A.M.
      • Kramer P.
      • Bui J.H.
      • et al.
      Targeted correction and restored function of the CFTR gene in cystic fibrosis induced pluripotent stem cells.
      Stem Cell Rep. 2015; 4: 569-577
      , 
      • Xia E.
      • Zhang Y.
      • Cao H.
      • et al.
      TALEN-Mediated Gene Targeting for Cystic Fibrosis-Gene Therapy.
      Genes. 2019; 10https://doi.org/10.3390/genes10010039
      , 
      • King N.E.
      • Suzuki S.
      • Barillà C.
      • et al.
      Correction of Airway Stem Cells: Genome Editing Approaches for the Treatment of Cystic Fibrosis.
      Hum Gene Ther. 2020; 31: 956-972
      We speculate that one day we will be able to turn back the clock on the development of clinical disease through very early intervention; such intervention is currently being investigated in animal models of CF and in trials of HEMT administration in infants and toddlers.
      • Egan M.E.
      Cystic fibrosis transmembrane conductance receptor modulator therapy in cystic fibrosis, an update.
      Curr Opin Pediatr. 2020; 32: 384-388
      ,
      • Guimbellot J.S.
      • Taylor-Cousar J.L.
      Combination CFTR modulator therapy in children and adults with cystic fibrosis.
      The Lancet Respir Med. 2021; 9: 677-679
      Finally, although we anticipate that recent advances will result in a smaller proportion of people with CF requiring lung transplantation or end-of-life care,
      • Lehr C.J.
      • Pilewski J.M.
      Cystic fibrosis: candidate selection and impact of the cystic fibrosis transmembrane conductance regulator therapy.
      Curr Opin Organ Transpl. 2022; https://doi.org/10.1097/MOT.0000000000000975
      the CF community remains committed to optimizing care for each individual with CF.
      In this issue of Clinics in Chest Medicine, we take stock of the gains enabled by the development of HEMT and consider the remaining challenges to assessing and improving the quantity and quality of life for all people with CF. As the clinical course and management of CF evolve in this new therapeutic era, we look forward to a promising and bright future in which CF-related morbidity is rare, health is maintained, and CF finally becomes a curable disease.

      References

        • Riordan J.R.
        • Rommens J.M.
        • Kerem B.
        • et al.
        Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
        Science. 1989; 245: 1066-1073
        View in Article
        • Davis P.B.
        Cystic fibrosis since 1938.
        Am J Respir Crit Care Med. 2006; 173: 475-482
        View in Article
        • Andersen D.H.
        Cystic fibrosis of the pancreas and its relation to celiac disease: a clinical and pathologic study.
        Am J Dis Child. 1938; 56: 344-399
        View in Article
      4. Patient Registry. Cystic Fibrosis Foundation.
        (Available at:)
        https://www.cff.org/medical-professionals/patient-registry
        (Accessed March 29, 2022)
        View in Article
        • McKone E.F.
        • Ariti C.
        • Jackson A.
        • et al.
        Survival estimates in European cystic fibrosis patients and the impact of socioeconomic factors: a retrospective registry cohort study.
        Eur Respir J. 2021; 58https://doi.org/10.1183/13993003.02288-2020
        View in Article
        • Stephenson A.L.
        • Sykes J.
        • Stanojevic S.
        • et al.
        Survival Comparison of Patients With Cystic Fibrosis in Canada and the United States: A Population-Based Cohort Study.
        Ann Intern Med. 2017; 166: 537-546
        View in Article
        • Hamosh A.
        • FitzSimmons S.C.
        • Macek Jr., M.
        • et al.
        Comparison of the clinical manifestations of cystic fibrosis in black and white patients.
        J Pediatr. 1998; 132: 255-259
        View in Article
        • Powers C.A.
        • Potter E.M.
        • Wessel H.U.
        • et al.
        Cystic fibrosis in Asian Indians.
        Arch Pediatr Adolesc Med. 1996; 150: 554-555
        View in Article
        • Yamashiro Y.
        • Shimizu T.
        • Oguchi S.
        • et al.
        The estimated incidence of cystic fibrosis in Japan.
        J Pediatr Gastroenterol Nutr. 1997; 24: 544-547
        View in Article
        • Stafler P.
        • Mei-Zahav M.
        • Wilschanski M.
        • et al.
        The impact of a national population carrier screening program on cystic fibrosis birth rate and age at diagnosis: Implications for newborn screening.
        J Cyst Fibros. 2016; 15: 460-466
        View in Article
        • Ramsey B.W.
        • Davies J.
        • McElvaney N.G.
        • et al.
        A CFTR potentiator in patients with cystic fibrosis and the G551D mutation.
        N Engl J Med. 2011; 365: 1663-1672
        View in Article
        • Taylor-Cousar J.L.
        • Munck A.
        • McKone E.F.
        • et al.
        Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del.
        N Engl J Med. 2017; 377: 2013-2023
        View in Article
        • Middleton P.G.
        • Mall M.A.
        • Dřevínek P.
        • et al.
        Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele.
        N Engl J Med. 2019; 381: 1809-1819
        View in Article
        • Koff J.
        Cystic Fibrosis, an Issue of Clinics in chest medicine.
        Elsevier Health Sciences, 2016
        View in Article
        • Gillan J.L.
        • Davidson D.J.
        • Gray R.D.
        Targeting cystic fibrosis inflammation in the age of CFTR modulators: focus on macrophages.
        Eur Respir J. 2021; 57https://doi.org/10.1183/13993003.03502-2020
        View in Article
        • Hisert K.B.
        • Birkland T.P.
        • Schoenfelt K.Q.
        • et al.
        Ivacaftor decreases monocyte sensitivity to interferon-γ in people with cystic fibrosis.
        ERJ Open Res. 2020; 6https://doi.org/10.1183/23120541.00318-2019
        View in Article
        • Jarosz-Griffiths H.H.
        • Scambler T.
        • Wong C.H.
        • et al.
        Different CFTR modulator combinations downregulate inflammation differently in cystic fibrosis.
        Elife. 2020; 9https://doi.org/10.7554/eLife.54556
        View in Article
        • Harris J.K.
        • Wagner B.D.
        • Zemanick E.T.
        • et al.
        Changes in Airway Microbiome and Inflammation with Ivacaftor Treatment in Patients with Cystic Fibrosis and the G551D Mutation.
        Ann Am Thorac Soc. 2020; 17: 212-220
        View in Article
        • Grasemann H.
        • Gonska T.
        • Avolio J.
        • et al.
        Effect of ivacaftor therapy on exhaled nitric oxide in patients with cystic fibrosis.
        J Cyst Fibros. 2015; 14: 727-732
        View in Article
        • Green M.
        • Lindgren N.
        • Henderson A.
        • et al.
        Ivacaftor partially corrects airway inflammation in a humanized G551D rat.
        Am J Physiol Lung Cell Mol Physiol. 2021; 320: L1093-L1100
        View in Article
        • Barnaby R.
        • Koeppen K.
        • Nymon A.
        • et al.
        Lumacaftor (VX-809) restores the ability of CF macrophages to phagocytose and kill Pseudomonas aeruginosa.
        Am J Physiol Lung Cell Mol Physiol. 2018; 314: L432-L438
        View in Article
        • Ruffin M.
        • Roussel L.
        • Maillé É.
        • et al.
        Vx-809/Vx-770 treatment reduces inflammatory response to Pseudomonas aeruginosa in primary differentiated cystic fibrosis bronchial epithelial cells.
        Am J Physiol Lung Cell Mol Physiol. 2018; 314: L635-L641
        View in Article
        • Clancy J.P.
        • Cotton C.U.
        • Donaldson S.H.
        • et al.
        CFTR modulator theratyping: Current status, gaps and future directions.
        J Cyst Fibros. 2019; 18: 22-34
        View in Article
        • Pedemonte N.
        • Zegarra-Moran O.
        • Galietta L.J.V.
        High-throughput screening of libraries of compounds to identify CFTR modulators.
        Methods Mol Biol. 2011; 741: 13-21
        View in Article
        • Sui J.
        • Cotard S.
        • Andersen J.
        • et al.
        Optimization of a Yellow fluorescent protein-based iodide influx high-throughput screening assay for cystic fibrosis transmembrane conductance regulator (CFTR) modulators.
        Assay Drug Dev Technol. 2010; 8: 656-668
        View in Article
        • Liang F.
        • Shang H.
        • Jordan N.J.
        • et al.
        High-Throughput Screening for Readthrough Modulators of CFTR PTC Mutations.
        SLAS Technol. 2017; 22: 315-324
        View in Article
        • Horsley A.R.
        • Belcher J.
        • Bayfield K.
        • et al.
        Longitudinal assessment of lung clearance index to monitor disease progression in children and adults with cystic fibrosis.
        Thorax. 2021; https://doi.org/10.1136/thoraxjnl-2021-216928
        View in Article
        • Smith L.
        • Aldag I.
        • Hughes P.
        • et al.
        Longitudinal monitoring of disease progression in children with mild CF using hyperpolarised gas MRI and LCI.
        Eur Respir J. 2016; 48https://doi.org/10.1183/13993003.congress-2016.OA284
        View in Article
        • Szczesniak R.
        • Turkovic L.
        • Andrinopoulou E.R.
        • et al.
        Chest imaging in cystic fibrosis studies: What counts, and can be counted?.
        J Cyst Fibros. 2017; 16: 175-185
        View in Article
        • Dournes G.
        • Walkup L.L.
        • Benlala I.
        • et al.
        The Clinical Use of Lung MRI in Cystic Fibrosis: What, Now, How?.
        Chest. 2021; 159: 2205-2217
        View in Article
        • Beswick D.M.
        • Humphries S.M.
        • Balkissoon C.D.
        • et al.
        Impact of CFTR Therapy on Chronic Rhinosinusitis and Health Status: Deep Learning CT Analysis and Patient Reported Outcomes.
        Ann Am Thorac Soc. 2021; https://doi.org/10.1513/AnnalsATS.202101-057OC
        View in Article
        • Sathe M.
        • Moshiree B.
        • Vu P.T.
        • et al.
        Utilization of electronic patient-reported outcome measures in cystic fibrosis research: Application to the GALAXY study.
        J Cyst Fibros. 2021; 20: 605-611
        View in Article
        • Ishak A.
        • Stick S.M.
        • Turkovic L.
        • et al.
        BAL Inflammatory Markers Can Predict Pulmonary Exacerbations in Children With Cystic Fibrosis.
        Chest. 2020; 158: 2314-2322
        View in Article
        • Khanal S.
        • Webster M.
        • Niu N.
        • et al.
        SPLUNC1: a novel marker of cystic fibrosis exacerbations.
        Eur Respir J. 2021; https://doi.org/10.1183/13993003.00507-2020
        View in Article
        • Payne J.E.
        • Dubois A.V.
        • Ingram R.J.
        • et al.
        Activity of innate antimicrobial peptides and ivacaftor against clinical cystic fibrosis respiratory pathogens.
        Int J Antimicrob Agents. 2017; 50: 427-435
        View in Article
        • 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: 68-79
        View in Article
        • Shteinberg M.
        • Taylor-Cousar J.L.
        • Durieu I.
        • et al.
        Fertility and Pregnancy in Cystic Fibrosis.
        Chest. 2021; https://doi.org/10.1016/j.chest.2021.07.024
        View in Article
        • Freeman A.J.
        • Sathe M.
        • Aliaj E.
        • et al.
        Designing the GALAXY study: Partnering with the cystic fibrosis community to optimize assessment of gastrointestinal symptoms.
        J Cyst Fibros. 2021; 20: 598-604
        View in Article
        • Smith S.
        • Rowbotham N.J.
        • Regan K.H.
        Inhaled anti-pseudomonal antibiotics for long-term therapy in cystic fibrosis.
        Cochrane Database Syst Rev. 2018; 3: CD001021
        View in Article
        • Abdalla M.Y.
        • Switzer B.L.
        • Goss C.H.
        • et al.
        Gallium Compounds Exhibit Potential as New Therapeutic Agents against Mycobacterium abscessus.
        Antimicrob Agents Chemother. 2015; 59: 4826-4834
        View in Article
        • Chan B.K.
        • Stanley G.
        • Modak M.
        • et al.
        Bacteriophage therapy for infections in CF.
        Pediatr Pulmonol. 2021; 56: S4-S9
        View in Article
        • Christopher Boyd A.
        • Guo S.
        • Huang L.
        • et al.
        New approaches to genetic therapies for cystic fibrosis.
        J Cyst Fibros. 2020; 19: S54-S59
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      DOI: https://doi.org/10.1016/j.ccm.2022.07.003

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      © 2022 Published by Elsevier Inc.

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