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Pulmonary Exacerbations

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Cystic Fibrosis

Part of the book series: Respiratory Medicine ((RM))

Abstract

Pulmonary exacerbations (PEx) are a frequent occurrence in the lives of individuals with cystic fibrosis (CF) and are associated with worsened morbidity, mortality, and quality of life. Approximately 25–35% individuals with CF don’t recover to 90% of baseline lung function after treatment for a PEx. Currently, there is scant evidence upon which to base guidelines for detection and management of PEx; therefore, the CF Foundation convened a working group to design and conduct clinical trials in order to establish evidence for best practices (Standardized Treatment of Pulmonary Exacerbations, STOP). The STOP program has conducted an observational study which has helped define the phenotype of PEx, characterize physician treatment practices, and evaluate clinical endpoints to use in future clinical trials. STOP-2 is an ongoing clinical trial of duration of antibiotics, which should guide establishment of best practices on duration. This chapter reviews the definition, epidemiology, current treatment practices, prognosis, and associated outcomes related to CF PEx. A patient perspective highlights the burden of PEx on the lives of individuals with CF. Current research is reviewed to clarify future directions in PEx. Upcoming clinical trials of PEx should provide robust clinical data in order to provide clear guidelines on detection and treatment of PEx.

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Abbreviations

CF:

Cystic Fibrosis

CFF:

Cystic Fibrosis Foundation

CFFPR:

Cystic Fibrosis Foundation Patient Registry

CFTR:

Cystic Fibrosis Transmembrane Conductance Regulator

ESCF:

Epidemiologic Study of Cystic Fibrosis

FEV1 :

Forced expiratory volume over 1 second

IV:

Intravenous

MRSA:

Methicillin-resistant Staphylococcus aureus

PEx:

Pulmonary exacerbations

PFTs:

Pulmonary Function Tests

PIPE:

Prednisone in Cystic Fibrosis Pulmonary Exacerbations

STOP:

Standardized Treatment of Pulmonary Exacerbations

References

  1. Ramsey BW, Boat TF. Outcome measures for clinical trials in cystic fibrosis. Summary of a Cystic Fibrosis Foundation consensus conference. J Pediatr. 1994;124:177–92.

    CAS  PubMed  Google Scholar 

  2. Marshall BC. Pulmonary exacerbations in cystic fibrosis: it’s time to be explicit! Am J Respir Crit Care Med. 2004;169:781–2.

    PubMed  Google Scholar 

  3. Flume PA, Mogayzel PJ, Robinson KA, Goss CH, Rosenblatt RL, Kuhn RJ, et al. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med. 2009;180:802–8.

    PubMed  Google Scholar 

  4. Morgan WJ, Butler SM, Johnson CA, Colin AA, FitzSimmons SC, Geller DE, et al. Epidemiologic study of cystic fibrosis: design and implementation of a prospective, multicenter, observational study of patients with cystic fibrosis in the U.S. and Canada. Pediatr Pulmonol. 1999;28:231–41.

    CAS  PubMed  Google Scholar 

  5. Konstan MW, Butler SM, Schidlow DV, Morgan WJ, Julius JR, Johnson CA. Patterns of medical practice in cystic fibrosis: part I. Evaluation and monitoring of health status of patients. Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Pediatr Pulmonol. 1999;28:242–7.

    CAS  PubMed  Google Scholar 

  6. Konstan MW, Butler SM, Schidlow DV, Morgan WJ, Julius JR, Johnson CA. Patterns of medical practice in cystic fibrosis: part II. Use of therapies. Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Pediatr Pulmonol. 1999;28:248–54.

    CAS  PubMed  Google Scholar 

  7. Johnson C, Butler SM, Konstan MW, Morgan W, Wohl ME. Factors influencing outcomes in cystic fibrosis: a center-based analysis. Chest. 2003;123:20–7.

    PubMed  Google Scholar 

  8. Schechter MS, Regelmann WE, Sawicki GS, Rasouliyan L, VanDevanter DR, Rosenfeld M, et al. Antibiotic treatment of signs and symptoms of pulmonary exacerbations: a comparison by care site. Pediatr Pulmonol. 2015;50:431–40.

    PubMed  Google Scholar 

  9. Kraynack NC, Gothard MD, Falletta LM, McBride JT. Approach to treating cystic fibrosis pulmonary exacerbations varies widely across US CF care centers. Pediatr Pulmonol. 2011;46:870–81.

    PubMed  Google Scholar 

  10. Wagener JS, Rasouliyan L, VanDevanter DR, Pasta DJ, Regelmann WE, Morgan WJ, et al. Oral, inhaled, and intravenous antibiotic choice for treating pulmonary exacerbations in cystic fibrosis. Pediatr Pulmonol. 2013;48:666–73.

    PubMed  Google Scholar 

  11. VanDevanter DR, O’Riordan MA, Blumer JL, Konstan MW. Assessing time to pulmonary function benefit following antibiotic treatment of acute cystic fibrosis exacerbations. Respir Res. 2010;11:137.

    PubMed  PubMed Central  Google Scholar 

  12. VanDevanter DR, Flume PA, Morris N, Konstan MW. Probability of IV antibiotic retreatment within thirty days is associated with duration and location of IV antibiotic treatment for pulmonary exacerbation in cystic fibrosis. J Cyst Fibros. 2016;15:783–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. VanDevanter DR, Morris NJ, Konstan MW. IV-treated pulmonary exacerbations in the prior year: an important independent risk factor for future pulmonary exacerbation in cystic fibrosis. J Cyst Fibros. 2016;15:372–9.

    PubMed  Google Scholar 

  14. Goss CH, Burns JL. Exacerbations in cystic fibrosis. 1: epidemiology and pathogenesis. Thorax. 2007;62:360–7.

    PubMed  PubMed Central  Google Scholar 

  15. Sanders DB, Solomon GM, Beckett VV, West NE, Daines CL, Heltshe SL, et al. Standardized Treatment of Pulmonary Exacerbations (STOP) study: observations at the initiation of intravenous antibiotics for cystic fibrosis pulmonary exacerbations. J Cyst Fibros. 2017;16:592–9.

    PubMed  PubMed Central  Google Scholar 

  16. West NE, Beckett VV, Jain R, Sanders DB, Nick JA, Heltshe SL, et al. Standardized Treatment of Pulmonary Exacerbations (STOP) study: physician treatment practices and outcomes for individuals with cystic fibrosis with pulmonary exacerbations. J Cyst Fibros. 2017;16:600–6.

    PubMed  PubMed Central  Google Scholar 

  17. Cystic Fibrosis Foundation. Cystic Fibrosis Foundation Patient Registry, 2017 annual data report. Bethesda. 2018.

    Google Scholar 

  18. Cogen JD, Oron AP, Gibson RL, Hoffman LR, Kronman MP, Ong T, et al. Characterization of inpatient cystic fibrosis pulmonary exacerbations. Pediatrics. 2017;139:e20162642.

    PubMed  PubMed Central  Google Scholar 

  19. Skolnik K, Quon BS. Recent advances in the understanding and management of cystic fibrosis pulmonary exacerbations. F1000Research. 2018;7:575.

    Google Scholar 

  20. Dentice RL, Elkins MR, Middleton PG, Bishop JR, Wark PAB, Dorahy DJ, et al. A randomised trial of hypertonic saline during hospitalisation for exacerbation of cystic fibrosis. Thorax. 2016;71:141–7.

    PubMed  Google Scholar 

  21. Wilmott RW, Amin RS, Colin AA, DeVault A, Dozor AJ, Eigen H, et al. Aerosolized recombinant human DNase in hospitalized cystic fibrosis patients with acute pulmonary exacerbations. Am J Respir Crit Care Med. 1996;153:1914–7.

    CAS  PubMed  Google Scholar 

  22. Dovey M, Aitken ML, Emerson J, McNamara S, Waltz DA, Gibson RL. Oral corticosteroid therapy in cystic fibrosis patients hospitalized for pulmonary exacerbation: a pilot study. Chest. 2007;132:1212–8.

    CAS  PubMed  Google Scholar 

  23. Hurley MN, Prayle AP, Flume P. Intravenous antibiotics for pulmonary exacerbations in people with cystic fibrosis. Cochrane Database Syst Rev [Internet]. 2015; Available from: https://doi.org/10.1002/14651858.CD009730.pub2.

  24. Heltshe SL, Goss CH, Thompson V, Sagel SD, Sanders DB, Marshall BC, et al. Short-term and long-term response to pulmonary exacerbation treatment in cystic fibrosis. Thorax. 2016;71:223–9.

    PubMed  Google Scholar 

  25. Nichols DP, Happoldt CL, Bratcher PE, Caceres SM, Chmiel JF, Malcolm KC, et al. Impact of azithromycin on the clinical and antimicrobial effectiveness of tobramycin in the treatment of cystic fibrosis. J Cyst Fibros. 2017;16:358–66.

    CAS  PubMed  Google Scholar 

  26. Bosworth DG, Nielson DW. Effectiveness of home versus hospital care in the routine treatment of cystic fibrosis. Pediatr Pulmonol. 1997;24:42–7.

    CAS  PubMed  Google Scholar 

  27. Schechter MS, VanDevanter DR, Pasta DJ, Short SA, Morgan WJ, Konstan MW, et al. Treatment setting and outcomes of cystic fibrosis pulmonary exacerbations. Ann Am Thorac Soc. 2018;15:225–33.

    PubMed  Google Scholar 

  28. Schechter MS, Schmidt HJ, Williams R, Norton R, Taylor D, Molzhon A. Impact of a program ensuring consistent response to acute drops in lung function in children with cystic fibrosis. J Cyst Fibros. 2018;17:769–78.

    PubMed  Google Scholar 

  29. Konstan MW, Wagener JS, VanDevanter DR, Pasta DJ, Yegin A, Rasouliyan L, et al. Risk factors for rate of decline in FEV1 in adults with cystic fibrosis. J Cyst Fibros. 2012;11:405–11.

    PubMed  PubMed Central  Google Scholar 

  30. Sanders DB, Hoffman LR, Emerson J, Gibson RL, Rosenfeld M, Redding GJ, et al. Return of FEV1 after pulmonary exacerbation in children with cystic fibrosis. Pediatr Pulmonol. 2010;45:127–34.

    PubMed  Google Scholar 

  31. Sanders DB, Bittner RC, Rosenfeld M, Redding GJ, Goss CH. Pulmonary exacerbations are associated with subsequent FEV1 decline in both adults and children with cystic fibrosis. Pediatr Pulmonol. 2011;46:393–400.

    PubMed  Google Scholar 

  32. 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;182:627–32.

    PubMed  PubMed Central  Google Scholar 

  33. Stanojevic S, McDonald A, Waters V, MacDonald S, Horton E, Tullis E, et al. Effect of pulmonary exacerbations treated with oral antibiotics on clinical outcomes in cystic fibrosis. Thorax. 2017;72:327.

    PubMed  Google Scholar 

  34. Kerem E, Reisman J, Corey M, Canny GJ, Levison H. Prediction of mortality in patients with cystic fibrosis. N Engl J Med. 1992;326:1187–91.

    CAS  PubMed  Google Scholar 

  35. Liou TG, Adler FR, Fitzsimmons SC, Cahill BC, Hibbs JR, Marshall BC. Predictive 5-year survivorship model of cystic fibrosis. Am J Epidemiol. 2001;153:345–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Mayer-Hamblett N, Rosenfeld M, Emerson J, Goss CH, Aitken ML. Developing cystic fibrosis lung transplant referral criteria using predictors of 2-year mortality. Am J Respir Crit Care Med. 2002;166:1550–5.

    PubMed  Google Scholar 

  37. Emerson J, Rosenfeld M, McNamara S, Ramsey B, Gibson RL. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol. 2002;34:91–100.

    PubMed  Google Scholar 

  38. Ellaffi M, Vinsonneau C, Coste J, Hubert D, Burgel PR, Dhainaut JF, et al. One-year outcome after severe pulmonary exacerbation in adults with cystic fibrosis. Am J Respir Crit Care Med. 2005;171:158–64.

    PubMed  Google Scholar 

  39. de Boer K, Vandemheen KL, Tullis E, Doucette S, Fergusson D, Freitag A, et al. Exacerbation frequency and clinical outcomes in adult patients with cystic fibrosis. Thorax. 2011;66:680–5.

    PubMed  Google Scholar 

  40. 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;121:64–72.

    PubMed  Google Scholar 

  41. Konstan MW, Morgan WJ, Butler SM, Pasta DJ, Craib ML, Silva SJ, et al. Risk factors for rate of decline in forced expiratory volume in one second in children and adolescents with cystic fibrosis. J Pediatr. 2007;151:134–9, 139.e1.

    PubMed  Google Scholar 

  42. Lieu TA, Ray GT, Farmer G, Shay GF. The cost of medical care for patients with cystic fibrosis in a health maintenance organization. Pediatrics. 1999;103:e72.

    CAS  PubMed  Google Scholar 

  43. Waters VJ, Stanojevic S, Sonneveld N, Klingel M, Grasemann H, Yau YC, et al. Factors associated with response to treatment of pulmonary exacerbations in cystic fibrosis patients. J Cyst Fibros. 2015;14:755–62.

    CAS  PubMed  Google Scholar 

  44. Waters V, Stanojevic S, Atenafu EG, Lu A, Yau Y, Tullis E, et al. Effect of pulmonary exacerbations on long-term lung function decline in cystic fibrosis. Eur Respir J. 2012;40:61–6.

    PubMed  Google Scholar 

  45. Hoppe JE, Wagner BD, Accurso FJ, Zemanick ET, Sagel SD. Characteristics and outcomes of oral antibiotic treated pulmonary exacerbations in children with cystic fibrosis. J Cyst Fibros. 2018;17(6):760–8.

    PubMed  PubMed Central  Google Scholar 

  46. Morgan WJ, Wagener JS, Pasta DJ, Millar SJ, VanDevanter DR, Konstan MW, et al. Relationship of antibiotic treatment to recovery after acute FEV1 decline in children with cystic fibrosis. Ann Am Thorac Soc. 2017;14:937–42.

    PubMed  Google Scholar 

  47. Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011;365:1663–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Flume PA, Wainwright CE, Elizabeth Tullis D, Rodriguez S, Niknian M, Higgins M, et al. Recovery of lung function following a pulmonary exacerbation in patients with cystic fibrosis and the G551D-CFTR mutation treated with ivacaftor. J Cyst Fibros. 2018;17:83–8.

    CAS  PubMed  Google Scholar 

  49. West NE, Flume PA. Unmet needs in cystic fibrosis: the next steps in improving outcomes. Expert Rev Respir Med. 2018;12:585–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. VanDevanter DR, Heltshe SL, Spahr J, Beckett VV, Daines CL, Dasenbrook EC, et al. Rationalizing endpoints for prospective studies of pulmonary exacerbation treatment response in cystic fibrosis. J Cyst Fibros. 2017;16:607–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Heltshe SL, West NE, VanDevanter DR, Sanders DB, Beckett VV, Flume PA, et al. Study design considerations for the Standardized Treatment of Pulmonary Exacerbations 2 (STOP2): a trial to compare intravenous antibiotic treatment durations in CF. Contemp Clin Trials. 2018;64:35–40.

    PubMed  Google Scholar 

  52. Sanders DB, Heltshe S, West NE, VanDevanter DR, Skalland M, Flume PA, et al. Update on the STOP-2 randomized study of IV antibiotic duration in CF pulmonary exacerbations. Pediatr Pulmonol. 2018;52:324.

    Google Scholar 

  53. Flume PA, Heltshe SL, West NE, Vandevanter DR, Sanders DB, Skalland M, et al. P094 Design, enrollment, and feasibility of the STOP-2 randomised study of intravenous antibiotic treatment duration in cystic fibrosis pulmonary exacerbations. J Cyst Fibros. 2018;17:S85.

    Google Scholar 

  54. Rosenfeld M, Davis R, FitzSimmons S, Pepe M, Ramsey B. Gender gap in cystic fibrosis mortality. Am J Epidemiol. 1997;145:794–803.

    CAS  PubMed  Google Scholar 

  55. Harness-Brumley CL, Elliott AC, Rosenbluth DB, Raghavan D, Jain R. Gender differences in outcomes of patients with cystic fibrosis. J Womens Health (Larchmt). 2014;23:1012–20.

    Google Scholar 

  56. Warwick WJ, Pogue RE, Gerber HU, Nesbitt CJ. Survival patterns in cyctic fibrosis. J Chronic Dis. 1975;28:609–22.

    CAS  PubMed  Google Scholar 

  57. FitzSimmons SC. The changing epidemiology of cystic fibrosis. J Pediatr. 1993;122:1–9.

    CAS  PubMed  Google Scholar 

  58. Sutton S, Rosenbluth D, Raghavan D, Zheng J, Jain R. Effects of puberty on cystic fibrosis related pulmonary exacerbations in women versus men. Pediatr Pulmonol. 2014;49:28–35.

    PubMed  Google Scholar 

  59. Dodge J, Lewis P, Stanton M, Wilsher J. Cystic fibrosis mortality and survival in the UK: 1947–2003. Eur Respir J. 2007;29:522–6.

    CAS  PubMed  Google Scholar 

  60. Block JK, Vandemheen KL, Tullis E, Fergusson D, Doucette S, Haase D, et al. Predictors of pulmonary exacerbations in patients with cystic fibrosis infected with multi-resistant bacteria. Thorax. 2006;61:969–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Chotirmall SH, Smith SG, Gunaratnam C, Cosgrove S, Dimitrov BD, O’Neill SJ, et al. Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis. N Engl J Med. 2012;366:1978–86.

    CAS  PubMed  Google Scholar 

  62. Coakley RD, Sun H, Clunes LA, Rasmussen JE, Stackhouse JR, Okada SF, et al. 17beta-Estradiol inhibits Ca2+-dependent homeostasis of airway surface liquid volume in human cystic fibrosis airway epithelia. J Clin Invest. 2008;118:4025–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Levy H, Kalish LA, Cannon CL, García KC, Gerard C, Goldmann D, et al. Predictors of mucoid Pseudomonas colonization in cystic fibrosis patients. Pediatr Pulmonol. 2008;43:463–71.

    PubMed  PubMed Central  Google Scholar 

  64. Maselli JH, Sontag MK, Norris JM, MacKenzie T, Wagener JS, Accurso FJ. Risk factors for initial acquisition of Pseudomonas aeruginosa in children with cystic fibrosis identified by newborn screening. Pediatr Pulmonol. 2003;35:257–62.

    PubMed  Google Scholar 

  65. Montemayor K, Dezube R, Lechtzin N, Jennings MT, Thaxton AL, Allgood S, et al. Sex differences in pulmonary exacerbations in cystic fibrosis patients. Am J Respir Crit Care Med. 2018;197:A6267.

    Google Scholar 

  66. Montemayor K, Dezube R, Lechtzin N, Psoter KJ, Jennings MT, Thaxton AL, et al. Sex differences in pulmonary exacerbations in cystic fibrosis patients. Pediatr Pulmonol. 2018;52:331.

    Google Scholar 

  67. Thornton J, Elliott R, Tully MP, Dodd M, Webb AK. Long term clinical outcome and hospital intravenous antibiotic treatment in adults with cystic fibrosis. Thorax. 2004;59:242–6.

    CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Johns Hopkins University, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Baltimore, MD, USA

    Kristina Montemayor & Natalie E. West

  2. University of Washington, Department of Medicine, Division of Pulmonary and Critical Care Medicine, WWAMI Spokane Foundations, UW at Schoenberg Center—Gonzaga, Spokane, WA, USA

    Allison A. Lambert

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  1. Kristina Montemayor
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  2. Allison A. Lambert
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  3. Natalie E. West
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Corresponding author

Correspondence to Natalie E. West .

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Editors and Affiliations

  1. The University of North Carolina at Chapel Hill, Department of Pediatrics, UNC Children’s Hospital, Chapel Hill, NC, USA

    Stephanie Duggins Davis

  2. Department of Pediatrics, University of Washington School of Medicine, Division of Pulmonary and Sleep Medicine, Seattle Children’s Hospital, Seattle, WA, USA

    Margaret Rosenfeld

  3. Department of Pediatrics, Indiana University School of Medicine, Division of Pediatric Pulmonology, Allergy and Sleep Medicine, Riley Hospital for Children at IU Health, Indianapolis, IN, USA

    James Chmiel

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Montemayor, K., Lambert, A.A., West, N.E. (2020). Pulmonary Exacerbations. In: Davis, S., Rosenfeld, M., Chmiel, J. (eds) Cystic Fibrosis. Respiratory Medicine. Humana, Cham. https://doi.org/10.1007/978-3-030-42382-7_9

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  • DOI: https://doi.org/10.1007/978-3-030-42382-7_9

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