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Semin Respir Crit Care Med 2023; 44(02): 196-208
DOI: 10.1055/s-0042-1758728
Review Article

Respiratory Viruses and Cystic Fibrosis

Kate Brackenborough
1   Oxford Centre for Respiratory Medicine, Oxford University Hospitals National Health Service Foundation Trust, Oxford, United Kingdom
,
Huw Ellis
1   Oxford Centre for Respiratory Medicine, Oxford University Hospitals National Health Service Foundation Trust, Oxford, United Kingdom
,
William G. Flight
1   Oxford Centre for Respiratory Medicine, Oxford University Hospitals National Health Service Foundation Trust, Oxford, United Kingdom
2   Research and Development, GlaxoSmithKline plc, Brentford, United Kingdom
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Abstract

The threat of respiratory virus infection to human health and well-being has been clearly highlighted by the coronavirus disease 2019 (COVID-19) pandemic. For people with cystic fibrosis (CF), the clinical significance of viral infections long predated the emergence of severe acute respiratory syndrome coronavirus 2. This article reviews the epidemiology, diagnosis, and treatment of respiratory virus infection in the context of CF as well as the current understanding of interactions between viruses and other microorganisms in the CF lung. The incidence of respiratory virus infection in CF varies by age with young children typically experiencing more frequent episodes than adolescents and adults. At all ages, respiratory viruses are very common in CF and are associated with pulmonary exacerbations. Respiratory viruses are identified at up to 69% of exacerbations, while viruses are also frequently detected during clinical stability. The full impact of COVID-19 in CF is yet to be established. Early studies found that rates of COVID-19 were lower in CF cohorts than in the general population. The reasons for this are unclear but may be related to the effects of shielding, infection control practices, maintenance CF therapies, or the inflammatory milieu in the CF lung. Observational studies have consistently identified that prior solid organ transplantation is a key risk factor for poor outcomes from COVID-19 in CF. Several key priorities for future research are highlighted. First, the impact of highly effective CFTR modulator therapy on the epidemiology and pathophysiology of viral infections in CF requires investigation. Second, the impact of respiratory viruses on the development and dynamics of the CF lung microbiota is poorly understood and viral infection may have important interactions with bacteria and fungi in the airway. Finally, bacteriophages represent a key focus of future investigation both for their role in transmission of antimicrobial resistance and as a promising treatment modality for multiresistant pathogens.

Keywords

COVID-19 - cystic fibrosis - influenza - microbiome - respiratory viruses - rhinovirus


Publication History

Article published online:
19 December 2022

© 2022. Thieme. All rights reserved.

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  • References

  • 1 Wang EE, Prober CG, Manson B, Corey M, Levison H. Association of respiratory viral infections with pulmonary deterioration in patients with cystic fibrosis. N Engl J Med 1984; 311 (26) 1653-1658
    CrossrefPubMedGoogle Scholar
  • 2 de Boer K, Vandemheen KL, Tullis E. et al. Exacerbation frequency and clinical outcomes in adult patients with cystic fibrosis. Thorax 2011; 66 (08) 680-685
    CrossrefPubMedGoogle Scholar
  • 3 Sanders DB, Bittner RC, Rosenfeld M, Hoffman LR, Redding GJ, Goss CH. Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation. Am J Respir Crit Care Med 2010; 182 (05) 627-632
    CrossrefPubMedGoogle Scholar
  • 4 Britto MT, Kotagal UR, Hornung RW, Atherton HD, Tsevat J, Wilmott RW. Impact of recent pulmonary exacerbations on quality of life in patients with cystic fibrosis. Chest 2002; 121 (01) 64-72
    CrossrefPubMedGoogle Scholar
  • 5 Monto AS, Ullman BM. Acute respiratory illness in an American community. The Tecumseh study. JAMA 1974; 227 (02) 164-169
    CrossrefPubMedGoogle Scholar
  • 6 Spigland I, Fox JP, Elveback LR. et al. The Virus Watch program: a continuing surveillance of viral infections in metropolitan New York families. II. Laboratory methods and preliminary report on infections revealed by virus isolation. Am J Epidemiol 1966; 83 (03) 413-435
    CrossrefPubMedGoogle Scholar
  • 7 Hiatt PW, Grace SC, Kozinetz CA. et al. Effects of viral lower respiratory tract infection on lung function in infants with cystic fibrosis. Pediatrics 1999; 103 (03) 619-626
    CrossrefPubMedGoogle Scholar
  • 8 van Ewijk BE, van der Zalm MM, Wolfs TF. et al. Prevalence and impact of respiratory viral infections in young children with cystic fibrosis: prospective cohort study. Pediatrics 2008; 122 (06) 1171-1176
    CrossrefPubMedGoogle Scholar
  • 9 Ramsey BW, Gore EJ, Smith AL, Cooney MK, Redding GJ, Foy H. The effect of respiratory viral infections on patients with cystic fibrosis. Am J Dis Child 1989; 143 (06) 662-668
    PubMedGoogle Scholar
  • 10 Korten I, Kieninger E, Klenja S. et al; SCILD and BILD study groups. Respiratory viruses in healthy infants and infants with cystic fibrosis: a prospective cohort study. Thorax 2018; 73 (01) 13-20
    CrossrefPubMedGoogle Scholar
  • 11 Brestovac B, Lawrence C, Speers DJ, Sammels LM, Mulrennan S. Respiratory viral infections in Western Australians with cystic fibrosis. Respir Med 2020; 161: 105854
    CrossrefPubMedGoogle Scholar
  • 12 Flight WG, Bright-Thomas RJ, Tilston P. et al. Incidence and clinical impact of respiratory viruses in adults with cystic fibrosis. Thorax 2014; 69 (03) 247-253
    CrossrefPubMedGoogle Scholar
  • 13 Smyth AR, Smyth RL, Tong CY, Hart CA, Heaf DP. Effect of respiratory virus infections including rhinovirus on clinical status in cystic fibrosis. Arch Dis Child 1995; 73 (02) 117-120
    CrossrefPubMedGoogle Scholar
  • 14 Wat D, Gelder C, Hibbitts S. et al. The role of respiratory viruses in cystic fibrosis. J Cyst Fibros 2008; 7 (04) 320-328
    CrossrefPubMedGoogle Scholar
  • 15 Hizal M, Yalcin E, Alp A. et al. Respiratory viruses: what is their role in acute exacerbations in children with cystic fibrosis?. Pediatr Pulmonol 2020; 55 (07) 1646-1652
    CrossrefPubMedGoogle Scholar
  • 16 Deschamp AR, Hatch JE, Slaven JE. et al. Early respiratory viral infections in infants with cystic fibrosis. J Cyst Fibros 2019; 18 (06) 844-850
    CrossrefPubMedGoogle Scholar
  • 17 Collinson J, Nicholson KG, Cancio E. et al. Effects of upper respiratory tract infections in patients with cystic fibrosis. Thorax 1996; 51 (11) 1115-1122
    CrossrefPubMedGoogle Scholar
  • 18 Olesen HV, Nielsen LP, Schiotz PO. Viral and atypical bacterial infections in the outpatient pediatric cystic fibrosis clinic. Pediatr Pulmonol 2006; 41 (12) 1197-1204
    CrossrefPubMedGoogle Scholar
  • 19 de Almeida MB, Zerbinati RM, Tateno AF. et al. Rhinovirus C and respiratory exacerbations in children with cystic fibrosis. Emerg Infect Dis 2010; 16 (06) 996-999
    CrossrefPubMedGoogle Scholar
  • 20 Shah A, Connelly M, Whitaker P. et al. Pathogenicity of individual rhinovirus species during exacerbations of cystic fibrosis. Eur Respir J 2015; 45 (06) 1748-1751
    CrossrefPubMedGoogle Scholar
  • 21 Flight W, Jones A. The diagnosis and management of respiratory viral infections in cystic fibrosis. Expert Rev Respir Med 2017; 11 (03) 221-227
    CrossrefPubMedGoogle Scholar
  • 22 Punch G, Syrmis MW, Rose BR. et al. Method for detection of respiratory viruses in the sputa of patients with cystic fibrosis. Eur J Clin Microbiol Infect Dis 2005; 24 (01) 54-57
    CrossrefPubMedGoogle Scholar
  • 23 Dijkema JS, van Ewijk BE, Wilbrink B, Wolfs TF, Kimpen JL, van der Ent CK. Frequency and duration of rhinovirus infections in children with cystic fibrosis and healthy controls: a longitudinal cohort study. Pediatr Infect Dis J 2016; 35 (04) 379-383
    CrossrefPubMedGoogle Scholar
  • 24 Eymery M, Morfin F, Doleans-Jordheim A. et al. Viral respiratory tract infections in young children with cystic fibrosis: a prospective full-year seasonal study. Virol J 2019; 16 (01) 111
    CrossrefPubMedGoogle Scholar
  • 25 Meyer VMC, Siqueira MM, Costa PFBM. et al. Clinical impact of respiratory virus in pulmonary exacerbations of children with cystic fibrosis. PLoS One 2020; 15 (10) e0240452
    CrossrefPubMedGoogle Scholar
  • 26 Goffard A, Lambert V, Salleron J. et al. Virus and cystic fibrosis: rhinoviruses are associated with exacerbations in adult patients. J Clin Virol 2014; 60 (02) 147-153
    CrossrefPubMedGoogle Scholar
  • 27 Etherington C, Naseer R, Conway SP, Whitaker P, Denton M, Peckham DG. The role of respiratory viruses in adult patients with cystic fibrosis receiving intravenous antibiotics for a pulmonary exacerbation. J Cyst Fibros 2014; 13 (01) 49-55
    CrossrefPubMedGoogle Scholar
  • 28 Gohil S, Donaghy B, Tature D. et al. Seasonal respiratory virus testing in management of adult cystic fibrosis patients. J Hosp Infect 2019; 103 (03) 360-361
    CrossrefPubMedGoogle Scholar
  • 29 Somayaji R, Goss CH, Khan U, Neradilek M, Neuzil KM, Ortiz JR. Cystic fibrosis pulmonary exacerbations attributable to respiratory syncytial virus and influenza: a population-based study. Clin Infect Dis 2017; 64 (12) 1760-1767
    CrossrefPubMedGoogle Scholar
  • 30 Conway SP, Simmonds EJ, Littlewood JM. Acute severe deterioration in cystic fibrosis associated with influenza A virus infection. Thorax 1992; 47 (02) 112-114
    CrossrefPubMedGoogle Scholar
  • 31 Gulla KM, Balaji A, Mukherjee A. et al. Course of Illness after viral infection in Indian children with cystic fibrosis. J Trop Pediatr 2019; 65 (02) 176-182
    CrossrefPubMedGoogle Scholar
  • 32 Bell SC, Mall MA, Gutierrez H. et al. The future of cystic fibrosis care: a global perspective. Lancet Respir Med 2020; 8 (01) 65-124
    CrossrefPubMedGoogle Scholar
  • 33 Mahony JB, Petrich A, Smieja M. Molecular diagnosis of respiratory virus infections. Crit Rev Clin Lab Sci 2011; 48 (5-6): 217-249
    CrossrefPubMedGoogle Scholar
  • 34 Zhu N, Zhang D, Wang W. et al; China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; 382 (08) 727-733
    CrossrefPubMedGoogle Scholar
  • 35 Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012; 367 (19) 1814-1820
    CrossrefPubMedGoogle Scholar
  • 36 Jones AM, Flight W, Isalska B. et al. Diagnosis of respiratory viral infections in cystic fibrosis by PCR using sputum samples. Eur Respir J 2011; 38 (06) 1486-1487
    CrossrefPubMedGoogle Scholar
  • 37 Cardot-Martin E, Guillou-Guillemette HL, Berre RL. et al. Sputum versus nasopharyngeal samples for the molecular diagnosis of respiratory viral infection in cystic fibrosis: a pilot study. J Cyst Fibros 2021; 20 (03) 432-435
    CrossrefPubMedGoogle Scholar
  • 38 Lee JJ, Verbakel JY, Goyder CR. et al. The clinical utility of point-of-care tests for influenza in ambulatory care: a systematic review and meta-analysis. Clin Infect Dis 2019; 69 (01) 24-33
    CrossrefPubMedGoogle Scholar
  • 39 Dinnes J, Deeks JJ, Berhane S. et al; Cochrane COVID-19 Diagnostic Test Accuracy Group. Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection. Cochrane Database Syst Rev 2021; 3: CD013705
    CrossrefPubMedGoogle Scholar
  • 40 Newton AH, Cardani A, Braciale TJ. The host immune response in respiratory virus infection: balancing virus clearance and immunopathology. Semin Immunopathol 2016; 38 (04) 471-482
    CrossrefPubMedGoogle Scholar
  • 41 Reijnders TDY, Schuurman AR, van der Poll T. The immune response to respiratory viruses: from start to memory. Semin Respir Crit Care Med 2021; 42 (06) 759-770
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID-19. Science 2022; 375 (6585): 1122-1127
    CrossrefPubMedGoogle Scholar
  • 43 Colasurdo GN, Fullmer JJ, Elidemir O, Atkins C, Khan AM, Stark JM. Respiratory syncytial virus infection in a murine model of cystic fibrosis. J Med Virol 2006; 78 (05) 651-658
    CrossrefPubMedGoogle Scholar
  • 44 Pittet LA, Hall-Stoodley L, Rutkowski MR, Harmsen AG. Influenza virus infection decreases tracheal mucociliary velocity and clearance of Streptococcus pneumoniae . Am J Respir Cell Mol Biol 2010; 42 (04) 450-460
    CrossrefPubMedGoogle Scholar
  • 45 Billard L, Le Berre R, Pilorgé L, Payan C, Héry-Arnaud G, Vallet S. Viruses in cystic fibrosis patients' airways. Crit Rev Microbiol 2017; 43 (06) 690-708
    CrossrefPubMedGoogle Scholar
  • 46 Pizurki L, Morris MA, Chanson M. et al. Cystic fibrosis transmembrane conductance regulator does not affect neutrophil migration across cystic fibrosis airway epithelial monolayers. Am J Pathol 2000; 156 (04) 1407-1416
    CrossrefPubMedGoogle Scholar
  • 47 Black HR, Yankaskas JR, Johnson LG, Noah TL. Interleukin-8 production by cystic fibrosis nasal epithelial cells after tumor necrosis factor-alpha and respiratory syncytial virus stimulation. Am J Respir Cell Mol Biol 1998; 19 (02) 210-215
    CrossrefPubMedGoogle Scholar
  • 48 Kieninger E, Vareille M, Kopf BS. et al. Lack of an exaggerated inflammatory response on virus infection in cystic fibrosis. Eur Respir J 2012; 39 (02) 297-304
    CrossrefPubMedGoogle Scholar
  • 49 Dauletbaev N, Das M, Cammisano M. et al. Rhinovirus load is high despite preserved interferon-β response in cystic fibrosis bronchial epithelial cells. PLoS One 2015; 10 (11) e0143129
    CrossrefPubMedGoogle Scholar
  • 50 Bodas M, Vij N. The NF-kappaB signaling in cystic fibrosis lung disease: pathophysiology and therapeutic potential. Discov Med 2010; 9 (47) 346-356
    PubMedGoogle Scholar
  • 51 Weber AJ, Soong G, Bryan R, Saba S, Prince A. Activation of NF-kappaB in airway epithelial cells is dependent on CFTR trafficking and Cl- channel function. Am J Physiol Lung Cell Mol Physiol 2001; 281 (01) L71-L78
    CrossrefPubMedGoogle Scholar
  • 52 Scagnolari C, Bitossi C, Frasca F. et al. Differential toll like receptor expression in cystic fibrosis patients' airways during rhinovirus infection. J Infect 2020; 81 (05) 726-735
    CrossrefPubMedGoogle Scholar
  • 53 Ling KM, Garratt LW, Gill EE. et al. Rhinovirus infection drives complex host airway molecular responses in children with cystic fibrosis. Front Immunol 2020; 11: 1327
    CrossrefPubMedGoogle Scholar
  • 54 Montgomery ST, Frey DL, Mall MA, Stick SM, Kicic A. AREST CF. Rhinovirus infection is associated with airway epithelial cell necrosis and inflammation via interleukin-1 in young children with cystic fibrosis. Front Immunol 2020; 11: 596
    CrossrefPubMedGoogle Scholar
  • 55 Xu W, Zheng S, Goggans TM. et al. Cystic fibrosis and normal human airway epithelial cell response to influenza a viral infection. J Interferon Cytokine Res 2006; 26 (09) 609-627
    CrossrefPubMedGoogle Scholar
  • 56 Sofoluwe A, Zoso A, Bacchetta M, Lemeille S, Chanson M. Immune response of polarized cystic fibrosis airway epithelial cells infected with Influenza A virus. J Cyst Fibros 2021; 20 (04) 655-663
    CrossrefPubMedGoogle Scholar
  • 57 Heijerman HGM, McKone EF, Downey DG. et al; VX17-445-103 Trial Group. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet 2019; 394 (10212): 1940-1948
    CrossrefPubMedGoogle Scholar
  • 58 Middleton PG, Mall MA, Dřevínek P. et al; VX17-445-102 Study Group. Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele. N Engl J Med 2019; 381 (19) 1809-1819
    CrossrefPubMedGoogle Scholar
  • 59 De Jong E, Garratt LW, Looi K. et al; WAERP. Ivacaftor or lumacaftor/ivacaftor treatment does not alter the core CF airway epithelial gene response to rhinovirus. J Cyst Fibros 2021; 20 (01) 97-105
    CrossrefPubMedGoogle Scholar
  • 60 Naehrlich L, Orenti A, Dunlevy F. et al; European Cystic Fibrosis COVID project group. Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020. J Cyst Fibros 2021; 20 (04) 566-577
    CrossrefPubMedGoogle Scholar
  • 61 Barr HL, Bihouee T, Zwitserloot AM. A year in review: real world evidence, functional monitoring and emerging therapeutics in 2021. J Cyst Fibros 2022; 21 (02) 191-196
    CrossrefPubMedGoogle Scholar
  • 62 Colombo C, Alicandro G, Daccó V. et al; Italian Cystic Fibrosis Society (SIFC) Study Group for COVID-19. SARS-CoV-2 infection in cystic fibrosis: a multicentre prospective study with a control group, Italy, February-July 2020. PLoS One 2021; 16 (05) e0251527
    CrossrefPubMedGoogle Scholar
  • 63 Colombo C, Cipolli M, Daccò V. et al. Clinical course and risk factors for severe COVID-19 among Italian patients with cystic fibrosis: a study within the Italian Cystic Fibrosis Society. Infection 2022; 50 (03) 671-679
    CrossrefPubMedGoogle Scholar
  • 64 Cosgriff R, Ahern S, Bell SC. et al; Global Registry Harmonization Group. A multinational report to characterise SARS-CoV-2 infection in people with cystic fibrosis. J Cyst Fibros 2020; 19 (03) 355-358
    CrossrefPubMedGoogle Scholar
  • 65 Mondejar-Lopez P, Quintana-Gallego E, Giron-Moreno RM. et al; CF-COVID19-Spain Registry Group. Impact of SARS-CoV-2 infection in patients with cystic fibrosis in Spain: incidence and results of the national CF-COVID19-Spain survey. Respir Med 2020; 170: 106062
    CrossrefPubMedGoogle Scholar
  • 66 McClenaghan E, Cosgriff R, Brownlee K. et al; Global Registry Harmonization Group. The global impact of SARS-CoV-2 in 181 people with cystic fibrosis. J Cyst Fibros 2020; 19 (06) 868-871
    CrossrefPubMedGoogle Scholar
  • 67 Bain R, Cosgriff R, Zampoli M. et al. Clinical characteristics of SARS-CoV-2 infection in children with cystic fibrosis: an international observational study. J Cyst Fibros 2021; 20 (01) 25-30
    CrossrefPubMedGoogle Scholar
  • 68 Rodkjær L, Jeppesen M, Schougaard L. Management of cystic fibrosis during covid-19: patient reported outcomes based remote follow-up among CF patients in Denmark—a feasibility study. J Cyst Fibros 2022; 21 (02) e106-e112
    CrossrefPubMedGoogle Scholar
  • 69 Mathew HR, Choi MY, Parkins MD, Fritzler MJ. Systematic review: cystic fibrosis in the SARS-CoV-2/COVID-19 pandemic. BMC Pulm Med 2021; 21 (01) 173
    CrossrefPubMedGoogle Scholar
  • 70 Dowd C, Van Citters AD, Dieni O, Willis A, Powell L, Sabadosa KA. Design and methods for understanding the state of cystic fibrosis care amid the COVID-19 pandemic. J Cyst Fibros 2021; 20 (Suppl 3): 3-8
    CrossrefPubMedGoogle Scholar
  • 71 Albon D, Van Citters AD, Ong T. et al. Telehealth use in cystic fibrosis during COVID-19: association with race, ethnicity, and socioeconomic factors. J Cyst Fibros 2021; 20 (Suppl. 03) 49-54
    CrossrefPubMedGoogle Scholar
  • 72 Sanders DB, Wu R, O'Neil T. et al. Changes in care during the COVID-19 pandemic for people with cystic fibrosis. Ann Am Thorac Soc 2022; 19 (Suppl. 10) 1697-1703
    CrossrefPubMedGoogle Scholar
  • 73 Dunk R, Madge S. SARS-CoV-2 driving rapid change in adult cystic fibrosis services: the role of the clinical nurse specialist. BMJ Open Qual 2021; 10 (04) 10
    CrossrefPubMedGoogle Scholar
  • 74 Somerville LAL, List RP, Compton MH. et al. Real-world outcomes in cystic fibrosis telemedicine clinical care in a time of a global pandemic. Chest 2022; 161 (05) 1167-1179
    CrossrefPubMedGoogle Scholar
  • 75 Saiman L, Siegel JD, LiPuma JJ. et al; Cystic Fibrous Foundation, Society for Healthcare Epidemiology of America. Infection prevention and control guideline for cystic fibrosis: 2013 update. Infect Control Hosp Epidemiol 2014; 35 (Suppl. 01) S1-S67
    CrossrefPubMedGoogle Scholar
  • 76 Chiner-Vives E, Cordovilla-Pérez R, de la Rosa-Carrillo D. et al. Short and long-term impact of COVID-19 infection on previous respiratory diseases. Arch Bronconeumol 2022; 58 (Suppl. 01) 39-50
    CrossrefPubMedGoogle Scholar
  • 77 Servidio AG, Capata G, Levantino L. et al. COVID-19 lockdown beneficial effects on lung function in a cohort of cystic fibrosis patients. Ital J Pediatr 2021; 47 (01) 12
    CrossrefPubMedGoogle Scholar
  • 78 Patel S, Thompson MD, Slaven JE, Sanders DB, Ren CL. Reduction of pulmonary exacerbations in young children with cystic fibrosis during the COVID-19 pandemic. Pediatr Pulmonol 2021; 56 (05) 1271-1273
    CrossrefPubMedGoogle Scholar
  • 79 Havermans T, Houben J, Vermeulen F. et al. The impact of the COVID-19 pandemic on the emotional well-being and home treatment of Belgian patients with cystic fibrosis, including transplanted patients and paediatric patients. J Cyst Fibros 2020; 19 (06) 880-887
    CrossrefPubMedGoogle Scholar
  • 80 Westcott KA, Wilkins F, Chancellor A. et al. The impact of COVID-19 shielding on the wellbeing, mental health and treatment adherence of adults with cystic fibrosis. Future Healthc J 2021; 8 (01) e47-e49
    CrossrefPubMedGoogle Scholar
  • 81 Ciprandi R, Bonati M, Campi R, Pescini R, Castellani C. Psychological distress in adults with and without cystic fibrosis during the COVID-19 lockdown. J Cyst Fibros 2021; 20 (02) 198-204
    CrossrefPubMedGoogle Scholar
  • 82 Smith BA, Georgiopoulos AM, Mueller A. et al. Impact of COVID-19 on mental health: effects on screening, care delivery, and people with cystic fibrosis. J Cyst Fibros 2021; 20 (Suppl 3): 31-38
    CrossrefPubMedGoogle Scholar
  • 83 Collaço N, Legg J, Day M. et al. COVID-19: impact, experiences, and support needs of children and young adults with cystic fibrosis and parents. Pediatr Pulmonol 2021; 56 (09) 2845-2853
    CrossrefPubMedGoogle Scholar
  • 84 Paynter A, Khan U, Heltshe SL, Goss CH, Lechtzin N, Hamblett NM. A comparison of clinic and home spirometry as longitudinal outcomes in cystic fibrosis. J Cyst Fibros 2022; 21 (01) 78-83
    CrossrefPubMedGoogle Scholar
  • 85 Calthorpe RJ, Smyth AR. Telehealth after the pandemic: will the inverse care law apply? (Commentary). J Cyst Fibros 2021; 20 (Suppl 3): 47-48
    CrossrefPubMedGoogle Scholar
  • 86 Dharmaraj P, Smyth RL. Vaccines for preventing influenza in people with cystic fibrosis. Cochrane Database Syst Rev 2014; (03) CD001753
    PubMedGoogle Scholar
  • 87 Mazur NI, Higgins D, Nunes MC. et al; Respiratory Syncytial Virus Network (ReSViNET) Foundation. The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates. Lancet Infect Dis 2018; 18 (10) e295-e311
    CrossrefPubMedGoogle Scholar
  • 88 Metz J, Eber E, Resch B. Respiratory syncytial virus infection-associated hospitalization rates in infants and children with cystic fibrosis. Pediatr Infect Dis J 2017; 36 (06) 545-548
    CrossrefPubMedGoogle Scholar
  • 89 Giebels K, Marcotte JE, Podoba J. et al. Prophylaxis against respiratory syncytial virus in young children with cystic fibrosis. Pediatr Pulmonol 2008; 43 (02) 169-174
    CrossrefPubMedGoogle Scholar
  • 90 Robinson KA, Odelola OA, Saldanha IJ. Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis. Cochrane Database Syst Rev 2016; 7: CD007743
    PubMedGoogle Scholar
  • 91 Dennis JB, Jones AM, Davies EA. et al. Influenza B outbreak at an adult cystic fibrosis centre—clinical impact and factors influencing spread. J Cyst Fibros 2020; 19 (05) 808-814
    CrossrefPubMedGoogle Scholar
  • 92 Uyeki TM, Bernstein HH, Bradley JS. et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenzaa. Clin Infect Dis 2019; 68 (06) e1-e47
    CrossrefPubMedGoogle Scholar
  • 93 Ison MG, Portsmouth S, Yoshida Y. et al. Early treatment with baloxavir marboxil in high-risk adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): a randomised, placebo-controlled, phase 3 trial. Lancet Infect Dis 2020; 20 (10) 1204-1214
    CrossrefPubMedGoogle Scholar
  • 94 Hayden FG, Sugaya N, Hirotsu N. et al; Baloxavir Marboxil Investigators Group. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med 2018; 379 (10) 913-923
    CrossrefPubMedGoogle Scholar
  • 95 Wright PF, Khaw KT, Oxman MN, Shwachman H. Evaluation of the safety of amantadine-HC1 and the role of respiratory viral infections in children with cystic fibrosis. J Infect Dis 1976; 134 (02) 144-149
    CrossrefPubMedGoogle Scholar
  • 96 Agarwal A, Rochwerg B, Lamontagne F. et al. A living WHO guideline on drugs for covid-19. BMJ 2020; 370: m3379
    PubMedGoogle Scholar
  • 97 Faust K, Raes J. Microbial interactions: from networks to models. Nat Rev Microbiol 2012; 10 (08) 538-550
    CrossrefPubMedGoogle Scholar
  • 98 Elborn JS. Cystic fibrosis. Lancet 2016; 388 (10059): 2519-2531
    CrossrefPubMedGoogle Scholar
  • 99 Surette MG. The cystic fibrosis lung microbiome. Ann Am Thorac Soc 2014; 11 (Suppl. 01) S61-S65
    CrossrefPubMedGoogle Scholar
  • 100 Asner S, Waters V, Solomon M. et al. Role of respiratory viruses in pulmonary exacerbations in children with cystic fibrosis. J Cyst Fibros 2012; 11 (05) 433-439
    CrossrefPubMedGoogle Scholar
  • 101 da Silva Filho LV, Zerbinati RM, Tateno AF. et al. The differential clinical impact of human coronavirus species in children with cystic fibrosis. J Infect Dis 2012; 206 (03) 384-388
    CrossrefPubMedGoogle Scholar
  • 102 Lopes SP, Azevedo NF, Pereira MO. Microbiome in cystic fibrosis: shaping polymicrobial interactions for advances in antibiotic therapy. Crit Rev Microbiol 2015; 41 (03) 353-365
    CrossrefPubMedGoogle Scholar
  • 103 Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis 2008; 198 (07) 962-970
    CrossrefPubMedGoogle Scholar
  • 104 Jennings LC, Anderson TP, Beynon KA. et al. Incidence and characteristics of viral community-acquired pneumonia in adults. Thorax 2008; 63 (01) 42-48
    CrossrefPubMedGoogle Scholar
  • 105 Templeton KE, Scheltinga SA, van den Eeden WC, Graffelman AW, van den Broek PJ, Claas EC. Improved diagnosis of the etiology of community-acquired pneumonia with real-time polymerase chain reaction. Clin Infect Dis 2005; 41 (03) 345-351
    CrossrefPubMedGoogle Scholar
  • 106 Petersen NT, Høiby N, Mordhorst CH, Lind K, Flensborg EW, Bruun B. Respiratory infections in cystic fibrosis patients caused by virus, chlamydia and mycoplasma–possible synergism with Pseudomonas aeruginosa . Acta Paediatr Scand 1981; 70 (05) 623-628
    CrossrefPubMedGoogle Scholar
  • 107 Chin M, De Zoysa M, Slinger R. et al. Acute effects of viral respiratory tract infections on sputum bacterial density during CF pulmonary exacerbations. J Cyst Fibros 2015; 14 (04) 482-489
    CrossrefPubMedGoogle Scholar
  • 108 Keravec M, Mounier J, Prestat E. et al. Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization. Springerplus 2015; 4: 405
    CrossrefPubMedGoogle Scholar
  • 109 Carmody LA, Zhao J, Schloss PD. et al. Changes in cystic fibrosis airway microbiota at pulmonary exacerbation. Ann Am Thorac Soc 2013; 10 (03) 179-187
    CrossrefPubMedGoogle Scholar
  • 110 Cuthbertson L, Rogers GB, Walker AW. et al. Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention. ISME J 2016; 10 (05) 1081-1091
    CrossrefPubMedGoogle Scholar
  • 111 Price KE, Hampton TH, Gifford AH. et al. Unique microbial communities persist in individual cystic fibrosis patients throughout a clinical exacerbation. Microbiome 2013; 1 (01) 27
    CrossrefPubMedGoogle Scholar
  • 112 Stressmann FA, Rogers GB, van der Gast CJ. et al. Long-term cultivation-independent microbial diversity analysis demonstrates that bacterial communities infecting the adult cystic fibrosis lung show stability and resilience. Thorax 2012; 67 (10) 867-873
    CrossrefPubMedGoogle Scholar
  • 113 Mallia P, Footitt J, Sotero R. et al. Rhinovirus infection induces degradation of antimicrobial peptides and secondary bacterial infection in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012; 186 (11) 1117-1124
    CrossrefPubMedGoogle Scholar
  • 114 Molyneaux PL, Mallia P, Cox MJ. et al. Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013; 188 (10) 1224-1231
    CrossrefPubMedGoogle Scholar
  • 115 Allen EK, Koeppel AF, Hendley JO, Turner SD, Winther B, Sale MM. Characterization of the nasopharyngeal microbiota in health and during rhinovirus challenge. Microbiome 2014; 2: 22
    CrossrefPubMedGoogle Scholar
  • 116 Ramos-Sevillano E, Wade WG, Mann A. et al. The effect of influenza virus on the human oropharyngeal microbiome. Clin Infect Dis 2019; 68 (12) 1993-2002
    CrossrefPubMedGoogle Scholar
  • 117 Yi H, Yong D, Lee K, Cho YJ, Chun J. Profiling bacterial community in upper respiratory tracts. BMC Infect Dis 2014; 14: 583
    CrossrefPubMedGoogle Scholar
  • 118 Bakaletz LO. Viral potentiation of bacterial superinfection of the respiratory tract. Trends Microbiol 1995; 3 (03) 110-114
    CrossrefPubMedGoogle Scholar
  • 119 Murphy TF, Bakaletz LO, Smeesters PR. Microbial interactions in the respiratory tract. Pediatr Infect Dis J 2009; 28 (10, suppl): S121-S126
    CrossrefPubMedGoogle Scholar
  • 120 Wang JH, Kwon HJ, Jang YJ. Rhinovirus enhances various bacterial adhesions to nasal epithelial cells simultaneously. Laryngoscope 2009; 119 (07) 1406-1411
    CrossrefPubMedGoogle Scholar
  • 121 Peltola VT, Murti KG, McCullers JA. Influenza virus neuraminidase contributes to secondary bacterial pneumonia. J Infect Dis 2005; 192 (02) 249-257
    CrossrefPubMedGoogle Scholar
  • 122 Shakhnovich EA, King SJ, Weiser JN. Neuraminidase expressed by Streptococcus pneumoniae desialylates the lipopolysaccharide of Neisseria meningitidis and Haemophilus influenzae: a paradigm for interbacterial competition among pathogens of the human respiratory tract. Infect Immun 2002; 70 (12) 7161-7164
    CrossrefPubMedGoogle Scholar
  • 123 McCullers JA. The co-pathogenesis of influenza viruses with bacteria in the lung. Nat Rev Microbiol 2014; 12 (04) 252-262
    CrossrefPubMedGoogle Scholar
  • 124 Nita-Lazar M, Banerjee A, Feng C. et al. Desialylation of airway epithelial cells during influenza virus infection enhances pneumococcal adhesion via galectin binding. Mol Immunol 2015; 65 (01) 1-16
    CrossrefPubMedGoogle Scholar
  • 125 Quattroni P, Li Y, Lucchesi D. et al. Galectin-3 binds Neisseria meningitidis and increases interaction with phagocytic cells. Cell Microbiol 2012; 14 (11) 1657-1675
    CrossrefPubMedGoogle Scholar
  • 126 Siegel SJ, Roche AM, Weiser JN. Influenza promotes pneumococcal growth during coinfection by providing host sialylated substrates as a nutrient source. Cell Host Microbe 2014; 16 (01) 55-67
    CrossrefPubMedGoogle Scholar
  • 127 Mansbach JM, Hasegawa K, Henke DM. et al. Respiratory syncytial virus and rhinovirus severe bronchiolitis are associated with distinct nasopharyngeal microbiota. J Allergy Clin Immunol 2016; 137 (06) 1909-1913.e4
    CrossrefPubMedGoogle Scholar
  • 128 Rosas-Salazar C, Shilts MH, Tovchigrechko A. et al. Differences in the nasopharyngeal microbiome during acute respiratory tract infection with human rhinovirus and respiratory syncytial virus in infancy. J Infect Dis 2016; 214 (12) 1924-1928
    CrossrefPubMedGoogle Scholar
  • 129 de Steenhuijsen Piters WA, Heinonen S, Hasrat R. et al. Nasopharyngeal microbiota, host transcriptome, and disease severity in children with respiratory syncytial virus infection. Am J Respir Crit Care Med 2016; 194 (09) 1104-1115
    CrossrefPubMedGoogle Scholar
  • 130 Teo SM, Mok D, Pham K. et al. The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe 2015; 17 (05) 704-715
    CrossrefPubMedGoogle Scholar
  • 131 Hyde ER, Petrosino JF, Piedra PA, Camargo Jr CA, Espinola JA, Mansbach JM. Nasopharyngeal Proteobacteria are associated with viral etiology and acute wheezing in children with severe bronchiolitis. J Allergy Clin Immunol 2014; 133 (04) 1220-1222
    CrossrefPubMedGoogle Scholar
  • 132 Bosch AATM, Levin E, van Houten MA. et al. Development of upper respiratory tract microbiota in infancy is affected by mode of delivery. EBioMedicine 2016; 9: 336-345
    CrossrefPubMedGoogle Scholar
  • 133 Biesbroek G, Bosch AA, Wang X. et al. The impact of breastfeeding on nasopharyngeal microbial communities in infants. Am J Respir Crit Care Med 2014; 190 (03) 298-308
    CrossrefPubMedGoogle Scholar
  • 134 Hasegawa K, Linnemann RW, Mansbach JM. et al. Nasal airway microbiota profile and severe bronchiolitis in infants: a case-control study. Pediatr Infect Dis J 2017; 36 (11) 1044-1051
    CrossrefPubMedGoogle Scholar
  • 135 Lynch JP, Sikder MA, Curren BF. et al. The influence of the microbiome on early-life severe viral lower respiratory infections and asthma-food for thought?. Front Immunol 2017; 8: 156
    CrossrefPubMedGoogle Scholar
  • 136 James KM, Gebretsadik T, Escobar GJ. et al. Risk of childhood asthma following infant bronchiolitis during the respiratory syncytial virus season. J Allergy Clin Immunol 2013; 132 (01) 227-229
    CrossrefPubMedGoogle Scholar
  • 137 Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B. Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med 2000; 161 (05) 1501-1507
    CrossrefPubMedGoogle Scholar
  • 138 Kusel MM, Kebadze T, Johnston SL, Holt PG, Sly PD. Febrile respiratory illnesses in infancy and atopy are risk factors for persistent asthma and wheeze. Eur Respir J 2012; 39 (04) 876-882
    CrossrefPubMedGoogle Scholar
  • 139 Jackson DJ, Gangnon RE, Evans MD. et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med 2008; 178 (07) 667-672
    CrossrefPubMedGoogle Scholar
  • 140 Wu P, Dupont WD, Griffin MR. et al. Evidence of a causal role of winter virus infection during infancy in early childhood asthma. Am J Respir Crit Care Med 2008; 178 (11) 1123-1129
    CrossrefPubMedGoogle Scholar
  • 141 Bisgaard H, Hermansen MN, Buchvald F. et al. Childhood asthma after bacterial colonization of the airway in neonates. N Engl J Med 2007; 357 (15) 1487-1495
    CrossrefPubMedGoogle Scholar
  • 142 Bisgaard H, Hermansen MN, Bønnelykke K. et al. Association of bacteria and viruses with wheezy episodes in young children: prospective birth cohort study. BMJ 2010; 341: c4978
    CrossrefPubMedGoogle Scholar
  • 143 Rosas-Salazar C, Shilts MH, Tovchigrechko A. et al. Nasopharyngeal Lactobacillus is associated with a reduced risk of childhood wheezing illnesses following acute respiratory syncytial virus infection in infancy. J Allergy Clin Immunol 2018; 142 (05) 1447-1456.e9
    CrossrefPubMedGoogle Scholar
  • 144 Willner D, Furlan M. Deciphering the role of phage in the cystic fibrosis airway. Virulence 2010; 1 (04) 309-313
    CrossrefPubMedGoogle Scholar
  • 145 Chanishvili N. Phage therapy–history from Twort and d'Herelle through Soviet experience to current approaches. Adv Virus Res 2012; 83: 3-40
    CrossrefPubMedGoogle Scholar
  • 146 Flight WG, Turkington CJR, Clokie MR. Viruses and the lung microbiome. In: Cox MJ, Ege MJ, von Mutius E. eds. The Lung Microbiome: European Respiratory Monograph. ERS; 2019: 119-139
    CrossrefGoogle Scholar
  • 147 Modi SR, Lee HH, Spina CS, Collins JJ. Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome. Nature 2013; 499 (7457): 219-222
    CrossrefPubMedGoogle Scholar
  • 148 Fancello L, Desnues C, Raoult D, Rolain JM. Bacteriophages and diffusion of genes encoding antimicrobial resistance in cystic fibrosis sputum microbiota. J Antimicrob Chemother 2011; 66 (11) 2448-2454
    CrossrefPubMedGoogle Scholar
  • 149 Brown-Jaque M, Rodriguez Oyarzun L, Cornejo-Sánchez T. et al. Detection of bacteriophage particles containing antibiotic resistance genes in the sputum of cystic fibrosis patients. Front Microbiol 2018; 9: 856
    CrossrefPubMedGoogle Scholar
  • 150 Abedon ST, Danis-Wlodarczyk KM, Alves DR. Phage therapy in the 21st century: is there modern, clinical evidence of phage-mediated efficacy?. Pharmaceuticals (Basel) 2021; 14 (11) 14
    Google Scholar
  • 151 Summers WC. Bacteriophage therapy. Annu Rev Microbiol 2001; 55: 437-451
    CrossrefPubMedGoogle Scholar
  • 152 Sulakvelidze A, Alavidze Z, Morris Jr JG. Bacteriophage therapy. Antimicrob Agents Chemother 2001; 45 (03) 649-659
    CrossrefPubMedGoogle Scholar
  • 153 Wright A, Hawkins CH, Anggård EE, Harper DR. A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy. Clin Otolaryngol 2009; 34 (04) 349-357
    CrossrefPubMedGoogle Scholar
  • 154 Waters EM, Neill DR, Kaman B. et al. Phage therapy is highly effective against chronic lung infections with Pseudomonas aeruginosa . Thorax 2017; 72 (07) 666-667
    CrossrefPubMedGoogle Scholar
  • 155 Martin I, Kenna DTD, Morales S, Alton EWFW, Davies JC. Variability in bacteriophage and antibiotic sensitivity in serial Pseudomonas aeruginosa isolates from cystic fibrosis airway cultures over 12 months. Microorganisms 2021; 9 (03) 9
    CrossrefPubMedGoogle Scholar
  • 156 Krylov V, Shaburova O, Pleteneva E. et al. Modular approach to select bacteriophages targeting Pseudomonas aeruginosa for their application to children suffering with cystic fibrosis. Front Microbiol 2016; 7: 1631
    CrossrefPubMedGoogle Scholar
  • 157 Kutateladze M, Adamia R. Phage therapy experience at the Eliava Institute. Med Mal Infect 2008; 38 (08) 426-430
    CrossrefPubMedGoogle Scholar
  • 158 Hoyle N, Zhvaniya P, Balarjishvili N. et al. Phage therapy against Achromobacter xylosoxidans lung infection in a patient with cystic fibrosis: a case report. Res Microbiol 2018; 169 (09) 540-542
    CrossrefPubMedGoogle Scholar
  • 159 Gainey AB, Burch AK, Brownstein MJ. et al. Combining bacteriophages with cefiderocol and meropenem/vaborbactam to treat a pan-drug resistant Achromobacter species infection in a pediatric cystic fibrosis patient. Pediatr Pulmonol 2020; 55 (11) 2990-2994
    CrossrefPubMedGoogle Scholar
  • 160 Dedrick RM, Guerrero-Bustamante CA, Garlena RA. et al. Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus . Nat Med 2019; 25 (05) 730-733
    CrossrefPubMedGoogle Scholar
  • 161 Lebeaux D, Merabishvili M, Caudron E. et al. A case of phage therapy against pandrug-resistant Achromobacter xylosoxidans in a 12-year-old lung-transplanted cystic fibrosis patient. Viruses 2021; 13 (01) 13
    CrossrefPubMedGoogle Scholar
  • 162 Nick JA, Dedrick RM, Gray AL. et al. Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection. Cell 2022; 185 (11) 1860-1874.e12
    CrossrefPubMedGoogle Scholar
  • 163 Kvachadze L, Balarjishvili N, Meskhi T. et al. Evaluation of lytic activity of staphylococcal bacteriophage Sb-1 against freshly isolated clinical pathogens. Microb Biotechnol 2011; 4 (05) 643-650
    CrossrefPubMedGoogle Scholar
  • 164 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 (04) 665-668
    CrossrefPubMedGoogle Scholar
  • 165 Aslam S, Courtwright AM, Koval C. et al. Early clinical experience of bacteriophage therapy in 3 lung transplant recipients. Am J Transplant 2019; 19 (09) 2631-2639
    CrossrefPubMedGoogle Scholar
  • 166 Dedrick RM, Freeman KG, Nguyen JA. et al. Potent antibody-mediated neutralization limits bacteriophage treatment of a pulmonary Mycobacterium abscessus infection. Nat Med 2021; 27 (08) 1357-1361
    CrossrefPubMedGoogle Scholar