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Cystic fibrosis: Overview of the treatment of lung disease

Author
Richard H Simon, MD
Section Editor
George B Mallory, MD
Deputy Editor
Alison G Hoppin, MD

INTRODUCTION

Cystic fibrosis (CF) is a multisystem disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, located on chromosome 7. Pulmonary disease remains the leading cause of morbidity and mortality in patients with CF. (See "Cystic fibrosis: Genetics and pathogenesis" and "Cystic fibrosis: Clinical manifestations and diagnosis".)

The treatment of CF lung disease is experiencing a period of rapid evolution, supported by well-designed clinical trials and improved understanding of the genetics and pathophysiology of the disease [1,2]. Undoubtedly, these advancements are responsible for a substantial portion of the improvement that has occurred in patient survival (figure 1).

While the focus of this discussion is on pulmonary therapies, it must be kept in mind that management is often suboptimal unless the multisystem nature of the disease is considered. Sinus infection, nutritional status, glucose control, and psychosocial issues must all be assessed at regular intervals. This requires a multidisciplinary approach to care that, in the United States, is best provided at one of the approximately 115 CF Care Centers (most with dedicated adult care programs) that are supported and accredited by the Cystic Fibrosis Foundation. Patients treated at these centers are seen on a regular basis by physicians, nurses, dietitians, respiratory therapists, physical therapists, and social workers with special competence in CF care. A listing of these centers can be obtained at the Cystic Fibrosis Foundation Web site (www.cff.org). In the United Kingdom, CF patients receiving their medical care at specialized CF centers have better clinical outcomes compared with patients followed in the general community [3,4]. In the United States, more frequent caregiver-patient interaction (visit frequency, monitoring, and interventions for pulmonary exacerbations) is associated with improved outcomes [5].

An overview of the treatment of CF lung disease will be reviewed here. Details of treatment with antibiotics are discussed separately. The diagnosis, clinical manifestations, and investigational treatments for CF are discussed separately. (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection" and "Cystic fibrosis: Clinical manifestations and diagnosis" and "Cystic fibrosis: Clinical manifestations of pulmonary disease" and "Cystic fibrosis: Investigational therapies".)

CFTR MODULATORS

CFTR modulators are a new class of drugs that act by improving function of the defective cystic fibrosis transmembrane regulator (CFTR) protein. The indications and efficacy of these drugs depend upon the CFTR mutation in the individual patient. Other CFTR modulators are in development. (See "Cystic fibrosis: Investigational therapies".)

                                              

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Literature review current through: Jul 2017. | This topic last updated: Aug 09, 2017.
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References
Top
  1. Stoltz DA, Meyerholz DK, Welsh MJ. Origins of cystic fibrosis lung disease. N Engl J Med 2015; 372:351.
  2. Ong T, Ramsey BW. Update in Cystic Fibrosis 2014. Am J Respir Crit Care Med 2015; 192:669.
  3. Mahadeva R, Webb K, Westerbeek RC, et al. Clinical outcome in relation to care in centres specialising in cystic fibrosis: cross sectional study. BMJ 1998; 316:1771.
  4. Mérelle ME, Schouten JP, Gerritsen J, Dankert-Roelse JE. Influence of neonatal screening and centralized treatment on long-term clinical outcome and survival of CF patients. Eur Respir J 2001; 18:306.
  5. Johnson C, Butler SM, Konstan MW, et al. Factors influencing outcomes in cystic fibrosis: a center-based analysis. Chest 2003; 123:20.
  6. Van Goor F, Hadida S, Grootenhuis PD, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci U S A 2009; 106:18825.
  7. Manufacturer's prescribing information for Kalydeco (ivacaftor) tablets. Available at: http://pi.vrtx.com/files/uspi_ivacaftor.pdf (Accessed on May 01, 2016).
  8. Kalydeco prescribing information, revised 5/2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/203188s019lbl.pdf (Accessed on June 01, 2017).
  9. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm559212.htm (Accessed on June 02, 2017).
  10. Davis PB. Therapy for cystic fibrosis--the end of the beginning? N Engl J Med 2011; 365:1734.
  11. Lahiri T, Hempstead SE, Brady C, et al. Clinical Practice Guidelines From the Cystic Fibrosis Foundation for Preschoolers With Cystic Fibrosis. Pediatrics 2016; 137.
  12. United States Food and Drug Administration, MedWatch, Safety labeling changes for Kalydeco (ivacaftor) tablets, December 2014. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm429779.htm (Accessed on January 31, 2015).
  13. 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; 365:1663.
  14. Davies JC, Wainwright CE, Canny GJ, et al. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med 2013; 187:1219.
  15. McKone EF, Borowitz D, Drevinek P, et al. Long-term safety and efficacy of ivacaftor in patients with cystic fibrosis who have the Gly551Asp-CFTR mutation: a phase 3, open-label extension study (PERSIST). Lancet Respir Med 2014; 2:902.
  16. Sawicki GS, McKone EF, Pasta DJ, et al. Sustained Benefit from ivacaftor demonstrated by combining clinical trial and cystic fibrosis patient registry data. Am J Respir Crit Care Med 2015; 192:836.
  17. Rowe SM, Heltshe SL, Gonska T, et al. Clinical mechanism of the cystic fibrosis transmembrane conductance regulator potentiator ivacaftor in G551D-mediated cystic fibrosis. Am J Respir Crit Care Med 2014; 190:175.
  18. Heltshe SL, Mayer-Hamblett N, Burns JL, et al. Pseudomonas aeruginosa in cystic fibrosis patients with G551D-CFTR treated with ivacaftor. Clin Infect Dis 2015; 60:703.
  19. Yu H, Burton B, Huang CJ, et al. Ivacaftor potentiation of multiple CFTR channels with gating mutations. J Cyst Fibros 2012; 11:237.
  20. De Boeck K, Munck A, Walker S, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. J Cyst Fibros 2014; 13:674.
  21. Van Goor F, Yu H, burton B, et al. Ivacaftor potentiates multiple mutant cystic fibrosis transconductance regulator (CFTR) forms [Abstract 31]. Pediatr Pulmonol Suppl 2012; 47:233.
  22. Moss RB, Flume PA, Elborn JS, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial. Lancet Respir Med 2015; 3:524.
  23. Manufacturer's prescribing information for Kalydeco (ivacaftor) tablets. Available at: http://pi.vrtx.com/files/uspi_ivacaftor.pdf (Accessed on March 26, 2015).
  24. Davies JC, Cunningham S, Harris WT, et al. Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. Lancet Respir Med 2016; 4:107.
  25. Manufacturer's prescribing information for Orkambi (lumacaftor/ivacaftor) tablets. Available at: http://pi.vrtx.com/files/uspi_lumacaftor_ivacaftor.pdf (Accessed on May 01, 2016).
  26. Flume PA, Liou TG, Borowitz DS, et al. Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del-CFTR mutation. Chest 2012; 142:718.
  27. Clancy JP, Rowe SM, Accurso FJ, et al. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax 2012; 67:12.
  28. Boyle MP, Bell SC, Konstan MW, et al. A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med 2014; 2:527.
  29. Wainwright CE, Elborn JS, Ramsey BW, et al. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N Engl J Med 2015; 373:220.
  30. Konstan MW, McKone EF, Moss RB, et al. Assessment of safety and efficacy of long-term treatment with combination lumacaftor and ivacaftor therapy in patients with cystic fibrosis homozygous for the F508del-CFTR mutation (PROGRESS): a phase 3, extension study. Lancet Respir Med 2017; 5:107.
  31. Milla CE, Ratjen F, Marigowda G, et al. Lumacaftor/Ivacaftor in Patients Aged 6-11 Years with Cystic Fibrosis and Homozygous for F508del-CFTR. Am J Respir Crit Care Med 2017; 195:912.
  32. Rowe SM, McColley SA, Rietschel E, et al. Lumacaftor/Ivacaftor Treatment of Patients with Cystic Fibrosis Heterozygous for F508del-CFTR. Ann Am Thorac Soc 2017; 14:213.
  33. Davis PB. Another Beginning for Cystic Fibrosis Therapy. N Engl J Med 2015; 373:274.
  34. Elborn JS, Ramsey BW, Boyle MP, et al. Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup: a pooled analysis. Lancet Respir Med 2016; 4:617.
  35. Ratjen F, Hug C, Marigowda G, et al. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial. Lancet Respir Med 2017; 5:557.
  36. Vertex pharmaceuticals press release 4/27/2016; Vertex Reports First Quarter 2016 Financial Results. Available at: http://investors.vrtx.com/releasedetail.cfm?ReleaseID=967156 (Accessed on April 30, 2016).
  37. Jennings MT, Dezube R, Paranjape S, et al. An Observational Study of Outcomes and Tolerances in Patients with Cystic Fibrosis Initiated on Lumacaftor/Ivacaftor. Ann Am Thorac Soc 2017.
  38. Elborn JS, Prescott RJ, Stack BH, et al. Elective versus symptomatic antibiotic treatment in cystic fibrosis patients with chronic Pseudomonas infection of the lungs. Thorax 2000; 55:355.
  39. Nir M, Lanng S, Johansen HK, Koch C. Long-term survival and nutritional data in patients with cystic fibrosis treated in a Danish centre. Thorax 1996; 51:1023.
  40. Breen L, Aswani N. Elective versus symptomatic intravenous antibiotic therapy for cystic fibrosis. Cochrane Database Syst Rev 2012; :CD002767.
  41. Mogayzel PJ Jr, Naureckas ET, Robinson KA, et al. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2013; 187:680.
  42. Weinberger M. Airways reactivity in patients with CF. Clin Rev Allergy Immunol 2002; 23:77.
  43. Stevens DA, Moss RB, Kurup VP, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis 2003; 37 Suppl 3:S225.
  44. Moss RB. Allergic bronchopulmonary aspergillosis and Aspergillus infection in cystic fibrosis. Curr Opin Pulm Med 2010; 16:598.
  45. Levine H, Cohen-Cymberknoh M, Klein N, et al. Reversible airway obstruction in cystic fibrosis: Common, but not associated with characteristics of asthma. J Cyst Fibros 2016; 15:652.
  46. Eggleston PA, Rosenstein BJ, Stackhouse CM, et al. A controlled trial of long-term bronchodilator therapy in cystic fibrosis. Chest 1991; 99:1088.
  47. König P, Gayer D, Barbero GJ, Shaffer J. Short-term and long-term effects of albuterol aerosol therapy in cystic fibrosis: a preliminary report. Pediatr Pulmonol 1995; 20:205.
  48. König P, Poehler J, Barbero GJ. A placebo-controlled, double-blind trial of the long-term effects of albuterol administration in patients with cystic fibrosis. Pediatr Pulmonol 1998; 25:32.
  49. Hordvik NL, Sammut PH, Judy CG, Colombo JL. Effectiveness and tolerability of high-dose salmeterol in cystic fibrosis. Pediatr Pulmonol 2002; 34:287.
  50. Ratjen F, Koker P, Geller DE, et al. Tiotropium Respimat in cystic fibrosis: Phase 3 and Pooled phase 2/3 randomized trials. J Cyst Fibros 2015; 14:608.
  51. Shak S. Aerosolized recombinant human DNase I for the treatment of cystic fibrosis. Chest 1995; 107:65S.
  52. Vasconcellos CA, Allen PG, Wohl ME, et al. Reduction in viscosity of cystic fibrosis sputum in vitro by gelsolin. Science 1994; 263:969.
  53. Fuchs HJ, Borowitz DS, Christiansen DH, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group. N Engl J Med 1994; 331:637.
  54. Flume PA, O'Sullivan BP, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2007; 176:957.
  55. Konstan MW, Wagener JS, Pasta DJ, et al. Clinical use of dornase alpha is associated with a slower rate of FEV1 decline in cystic fibrosis. Pediatr Pulmonol 2011; 46:545.
  56. Yang C, Chilvers M, Montgomery M, Nolan SJ. Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev 2016; 4:CD001127.
  57. Suri R, Metcalfe C, Lees B, et al. Comparison of hypertonic saline and alternate-day or daily recombinant human deoxyribonuclease in children with cystic fibrosis: a randomised trial. Lancet 2001; 358:1316.
  58. Suri R, Grieve R, Normand C, et al. Effects of hypertonic saline, alternate day and daily rhDNase on healthcare use, costs and outcomes in children with cystic fibrosis. Thorax 2002; 57:841.
  59. Cystic Fibrosis Foundation Patient Registry. 2014 Annual Data Report. Bethesda, Maryland Available at: www.cff.org/2014-Annual-Data-Report/ (Accessed on May 01, 2016).
  60. Cystic Fibrosis Foundation, Borowitz D, Robinson KA, et al. Cystic Fibrosis Foundation evidence-based guidelines for management of infants with cystic fibrosis. J Pediatr 2009; 155:S73.
  61. Berge MT, Wiel Ev, Tiddens HA, et al. DNase in stable cystic fibrosis infants: a pilot study. J Cyst Fibros 2003; 2:183.
  62. Donaldson SH, Bennett WD, Zeman KL, et al. Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med 2006; 354:241.
  63. Elkins MR, Robinson M, Rose BR, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med 2006; 354:229.
  64. Wark P, McDonald VM. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev 2009; :CD001506.
  65. Rosenfeld M, Ratjen F, Brumback L, et al. Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial. JAMA 2012; 307:2269.
  66. Dasenbrook EC, Konstan MW. Inhaled hypertonic saline in infants and young children with cystic fibrosis. JAMA 2012; 307:2316.
  67. Elkins M, Dentice R. Timing of hypertonic saline inhalation for cystic fibrosis. Cochrane Database Syst Rev 2016; 12:CD008816.
  68. Dentice RL, Elkins MR, Bye PT. Adults with cystic fibrosis prefer hypertonic saline before or during airway clearance techniques: a randomised crossover trial. J Physiother 2012; 58:33.
  69. Cystic Fibrosis Foundation Annual Patient Registry Report, 2013. Available from the Cystic Fibrosis Foundation, at: http://www.cff.org/ (Accessed on December 15, 2014).
  70. Tam J, Nash EF, Ratjen F, et al. Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis. Cochrane Database Syst Rev 2013; :CD007168.
  71. Flume PA, Robinson KA, O'Sullivan BP, et al. Cystic fibrosis pulmonary guidelines: airway clearance therapies. Respir Care 2009; 54:522.
  72. Lester MK, Flume PA. Airway-clearance therapy guidelines and implementation. Respir Care 2009; 54:733.
  73. Warnock L, Gates A. Chest physiotherapy compared to no chest physiotherapy for cystic fibrosis. Cochrane Database Syst Rev 2015; :CD001401.
  74. McIlwaine M, Wong LT, Chilvers M, Davidson GF. Long-term comparative trial of two different physiotherapy techniques; postural drainage with percussion and autogenic drainage, in the treatment of cystic fibrosis. Pediatr Pulmonol 2010; 45:1064.
  75. McIlwaine PM, Wong LT, Peacock D, Davidson AG. Long-term comparative trial of conventional postural drainage and percussion versus positive expiratory pressure physiotherapy in the treatment of cystic fibrosis. J Pediatr 1997; 131:570.
  76. McIlwaine MP, Alarie N, Davidson GF, et al. Long-term multicentre randomised controlled study of high frequency chest wall oscillation versus positive expiratory pressure mask in cystic fibrosis. Thorax 2013; 68:746.
  77. Sontag MK, Quittner AL, Modi AC, et al. Lessons learned from a randomized trial of airway secretion clearance techniques in cystic fibrosis. Pediatr Pulmonol 2010; 45:291.
  78. Main E. Airway clearance research in CF: the 'perfect storm' of strong preference and effortful participation in long-term, non-blinded studies. Thorax 2013; 68:701.
  79. Arias Llorente RP, Bousoño García C, Díaz Martín JJ. Treatment compliance in children and adults with cystic fibrosis. J Cyst Fibros 2008; 7:359.
  80. Oermann CM, Swank PR, Sockrider MM. Validation of an instrument measuring patient satisfaction with chest physiotherapy techniques in cystic fibrosis. Chest 2000; 118:92.
  81. Radtke T, Nolan SJ, Hebestreit H, Kriemler S. Physical exercise training for cystic fibrosis. Cochrane Database Syst Rev 2015; :CD002768.
  82. Schneiderman-Walker J, Pollock SL, Corey M, et al. A randomized controlled trial of a 3-year home exercise program in cystic fibrosis. J Pediatr 2000; 136:304.
  83. Rovedder PM, Flores J, Ziegler B, et al. Exercise programme in patients with cystic fibrosis: a randomized controlled trial. Respir Med 2014; 108:1134.
  84. Chmiel JF, Konstan MW. Inflammation and anti-inflammatory therapies for cystic fibrosis. Clin Chest Med 2007; 28:331.
  85. Saiman L, Marshall BC, Mayer-Hamblett N, et al. Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA 2003; 290:1749.
  86. Saiman L, Mayer-Hamblett N, Campbell P, et al. Heterogeneity of treatment response to azithromycin in patients with cystic fibrosis. Am J Respir Crit Care Med 2005; 172:1008.
  87. Shimizu T, Shimizu S, Hattori R, et al. In vivo and in vitro effects of macrolide antibiotics on mucus secretion in airway epithelial cells. Am J Respir Crit Care Med 2003; 168:581.
  88. Equi A, Balfour-Lynn IM, Bush A, Rosenthal M. Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial. Lancet 2002; 360:978.
  89. Wolter J, Seeney S, Bell S, et al. Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial. Thorax 2002; 57:212.
  90. Clement A, Tamalet A, Leroux E, et al. Long term effects of azithromycin in patients with cystic fibrosis: A double blind, placebo controlled trial. Thorax 2006; 61:895.
  91. Saiman L, Anstead M, Mayer-Hamblett N, et al. Effect of azithromycin on pulmonary function in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA 2010; 303:1707.
  92. Southern KW, Barker PM, Solis-Moya A, Patel L. Macrolide antibiotics for cystic fibrosis. Cochrane Database Syst Rev 2012; 11:CD002203.
  93. Moskowitz SM, Foster JM, Emerson J, Burns JL. Clinically feasible biofilm susceptibility assay for isolates of Pseudomonas aeruginosa from patients with cystic fibrosis. J Clin Microbiol 2004; 42:1915.
  94. Hoffmann N, Lee B, Hentzer M, et al. Azithromycin blocks quorum sensing and alginate polymer formation and increases the sensitivity to serum and stationary-growth-phase killing of Pseudomonas aeruginosa and attenuates chronic P. aeruginosa lung infection in Cftr(-/-) mice. Antimicrob Agents Chemother 2007; 51:3677.
  95. Wagner T, Burns JL. Anti-inflammatory properties of macrolides. Pediatr Infect Dis J 2007; 26:75.
  96. Ratjen F, Saiman L, Mayer-Hamblett N, et al. Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa. Chest 2012; 142:1259.
  97. Binder AM, Adjemian J, Olivier KN, Prevots DR. Epidemiology of nontuberculous mycobacterial infections and associated chronic macrolide use among persons with cystic fibrosis. Am J Respir Crit Care Med 2013; 188:807.
  98. Konstan MW, Byard PJ, Hoppel CL, Davis PB. Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med 1995; 332:848.
  99. Lands LC, Milner R, Cantin AM, et al. High-dose ibuprofen in cystic fibrosis: Canadian safety and effectiveness trial. J Pediatr 2007; 151:249.
  100. Lands LC, Stanojevic S. Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis. Cochrane Database Syst Rev 2016; 4:CD001505.
  101. Arranz I, Martín-Suárez A, Lanao JM, et al. Population pharmacokinetics of high dose ibuprofen in cystic fibrosis. Arch Dis Child 2003; 88:1128.
  102. Auerbach HS, Williams M, Kirkpatrick JA, Colten HR. Alternate-day prednisone reduces morbidity and improves pulmonary function in cystic fibrosis. Lancet 1985; 2:686.
  103. Eigen H, Rosenstein BJ, FitzSimmons S, Schidlow DV. A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis. Cystic Fibrosis Foundation Prednisone Trial Group. J Pediatr 1995; 126:515.
  104. Lai HC, FitzSimmons SC, Allen DB, et al. Risk of persistent growth impairment after alternate-day prednisone treatment in children with cystic fibrosis. N Engl J Med 2000; 342:851.
  105. Bisgaard H, Pedersen SS, Nielsen KG, et al. Controlled trial of inhaled budesonide in patients with cystic fibrosis and chronic bronchopulmonary Psuedomonas aeruginosa infection. Am J Respir Crit Care Med 1997; 156:1190.
  106. Nikolaizik WH, Schöni MH. Pilot study to assess the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis. J Pediatr 1996; 128:271.
  107. van Haren EH, Lammers JW, Festen J, et al. The effects of the inhaled corticosteroid budesonide on lung function and bronchial hyperresponsiveness in adult patients with cystic fibrosis. Respir Med 1995; 89:209.
  108. Balfour-Lynn IM, Lees B, Hall P, et al. Multicenter randomized controlled trial of withdrawal of inhaled corticosteroids in cystic fibrosis. Am J Respir Crit Care Med 2006; 173:1356.
  109. Balfour-Lynn IM, Welch K. Inhaled corticosteroids for cystic fibrosis. Cochrane Database Syst Rev 2014; :CD001915.
  110. Allen DB. Effects of inhaled steroids on growth, bone metabolism, and adrenal function. Adv Pediatr 2006; 53:101.
  111. De Boeck K, De Baets F, Malfroot A, et al. Do inhaled corticosteroids impair long-term growth in prepubertal cystic fibrosis patients? Eur J Pediatr 2007; 166:23.
  112. Sivan Y, Arce P, Eigen H, et al. A double-blind, randomized study of sodium cromoglycate versus placebo in patients with cystic fibrosis and bronchial hyperreactivity. J Allergy Clin Immunol 1990; 85:649.
  113. Guevara JP, Ducharme FM, Keren R, et al. Inhaled corticosteroids versus sodium cromoglycate in children and adults with asthma. Cochrane Database Syst Rev 2006; :CD003558.
  114. Viviani L, Assael BM, Kerem E, ECFS (A) H1N1 study group. Impact of the A (H1N1) pandemic influenza (season 2009-2010) on patients with cystic fibrosis. J Cyst Fibros 2011; 10:370.
  115. Jain M, Thomson AH. Palivizumab, pneumococcal and influenza vaccination in cystic fibrosis. J R Soc Med 2009; 102 Suppl 1:23.
  116. Malfroot A, Adam G, Ciofu O, et al. Immunisation in the current management of cystic fibrosis patients. J Cyst Fibros 2005; 4:77.
  117. Linnane B, Kiernan MG, O'Connell NH, et al. Anti-RSV prophylaxis efficacy for infants and young children with cystic fibrosis in Ireland. Multidiscip Respir Med 2015; 10:32.
  118. Groves HE, Jenkins L, Macfarlane M, et al. Efficacy and long-term outcomes of palivizumab prophylaxis to prevent respiratory syncytial virus infection in infants with cystic fibrosis in Northern Ireland. Pediatr Pulmonol 2016; 51:379.
  119. 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.
  120. American Academy of Pediatrics Committee on Infectious Diseases, American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics 2014; 134:415.
  121. Elphick HE, Mallory G. Oxygen therapy for cystic fibrosis. Cochrane Database Syst Rev 2013; :CD003884.
  122. Zinman R, Corey M, Coates AL, et al. Nocturnal home oxygen in the treatment of hypoxemic cystic fibrosis patients. J Pediatr 1989; 114:368.
  123. Yankaskas JR, Marshall BC, Sufian B, et al. Cystic fibrosis adult care: consensus conference report. Chest 2004; 125:1S.
  124. Granton JT, Shapiro C, Kesten S. Noninvasive nocturnal ventilatory support in advanced lung disease from cystic fibrosis. Respir Care 2002; 47:675.
  125. Young AC, Wilson JW, Kotsimbos TC, Naughton MT. Randomised placebo controlled trial of non-invasive ventilation for hypercapnia in cystic fibrosis. Thorax 2008; 63:72.
  126. Moran F, Bradley JM, Piper AJ. Non-invasive ventilation for cystic fibrosis. Cochrane Database Syst Rev 2017; 2:CD002769.
  127. Davis PB, di Sant'Agnese PA. Assisted ventilation for patients with cystic fibrosis. JAMA 1978; 239:1851.
  128. Madden BP, Kariyawasam H, Siddiqi AJ, et al. Noninvasive ventilation in cystic fibrosis patients with acute or chronic respiratory failure. Eur Respir J 2002; 19:310.
  129. Texereau J, Jamal D, Choukroun G, et al. Determinants of mortality for adults with cystic fibrosis admitted in Intensive Care Unit: a multicenter study. Respir Res 2006; 7:14.
  130. Sood N, Paradowski LJ, Yankaskas JR. Outcomes of intensive care unit care in adults with cystic fibrosis. Am J Respir Crit Care Med 2001; 163:335.
  131. Vedam H, Moriarty C, Torzillo PJ, et al. Improved outcomes of patients with cystic fibrosis admitted to the intensive care unit. J Cyst Fibros 2004; 3:8.
  132. Ellaffi M, Vinsonneau C, Coste J, et al. One-year outcome after severe pulmonary exacerbation in adults with cystic fibrosis. Am J Respir Crit Care Med 2005; 171:158.
  133. Efrati O, Bylin I, Segal E, et al. Outcome of patients with cystic fibrosis admitted to the intensive care unit: is invasive mechanical ventilation a risk factor for death in patients waiting lung transplantation? Heart Lung 2010; 39:153.
  134. Slieker MG, van Gestel JP, Heijerman HG, et al. Outcome of assisted ventilation for acute respiratory failure in cystic fibrosis. Intensive Care Med 2006; 32:754.
  135. Jones A, Bilton D, Evans TW, Finney SJ. Predictors of outcome in patients with cystic fibrosis requiring endotracheal intubation. Respirology 2013; 18:630.
  136. Morrell MR, Pilewski JM. Lung Transplantation for Cystic Fibrosis. Clin Chest Med 2016; 37:127.
  137. Goldfarb SB, Benden C, Edwards LB, et al. The Registry of the International Society for Heart and Lung Transplantation: Eighteenth Official Pediatric Lung and Heart-Lung Transplantation Report--2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant 2015; 34:1255.
  138. Yusen RD, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Lung and Heart-Lung Transplantation Report--2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant 2015; 34:1264.
  139. Liou TG, Adler FR, Cahill BC, et al. Survival effect of lung transplantation among patients with cystic fibrosis. JAMA 2001; 286:2683.
  140. Liou TG, Adler FR, Fitzsimmons SC, et al. Predictive 5-year survivorship model of cystic fibrosis. Am J Epidemiol 2001; 153:345.
  141. Weill D, Benden C, Corris PA, et al. A consensus document for the selection of lung transplant candidates: 2014--an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2015; 34:1.
  142. Organ Procurement and Transplantation Network. Hear & Lung. Health Resources and Services Administration, U.S. Department of Health & Human Services. https://optn.transplant.hrsa.gov/resources/by-organ/heart-lung/ (Accessed on April 30, 2016).
  143. Solé A, Pérez I, Vázquez I, et al. Patient-reported symptoms and functioning as indicators of mortality in advanced cystic fibrosis: A new tool for referral and selection for lung transplantation. J Heart Lung Transplant 2016; 35:789.
  144. Braun AT, Dasenbrook EC, Shah AS, et al. Impact of lung allocation score on survival in cystic fibrosis lung transplant recipients. J Heart Lung Transplant 2015; 34:1436.
  145. Schechter MA, Ganapathi AM, Englum BR, et al. Spontaneously Breathing Extracorporeal Membrane Oxygenation Support Provides the Optimal Bridge to Lung Transplantation. Transplantation 2016; 100:2699.
  146. United Network for Organ Sharing. OPTN/UNOS Board approves policy to increase lung transplant access for children, establishes criteria for programs performing pediatric transplants. https://www.unos.org/optnunos-board-approves-policy-to-increase-lung-transplant-access-for-children-establishes-criteria-for-programs-performing-pediatric-transplants/ (Accessed on May 01, 2016).
  147. Murray S, Charbeneau J, Marshall BC, LiPuma JJ. Impact of burkholderia infection on lung transplantation in cystic fibrosis. Am J Respir Crit Care Med 2008; 178:363.
  148. Boussaud V, Guillemain R, Grenet D, et al. Clinical outcome following lung transplantation in patients with cystic fibrosis colonised with Burkholderia cepacia complex: results from two French centres. Thorax 2008; 63:732.
  149. Alexander BD, Petzold EW, Reller LB, et al. Survival after lung transplantation of cystic fibrosis patients infected with Burkholderia cepacia complex. Am J Transplant 2008; 8:1025.
  150. De Soyza A, Meachery G, Hester KL, et al. Lung transplantation for patients with cystic fibrosis and Burkholderia cepacia complex infection: a single-center experience. J Heart Lung Transplant 2010; 29:1395.
  151. Hadjiliadis D, Steele MP, Chaparro C, et al. Survival of lung transplant patients with cystic fibrosis harboring panresistant bacteria other than Burkholderia cepacia, compared with patients harboring sensitive bacteria. J Heart Lung Transplant 2007; 26:834.
  152. Lobo LJ, Chang LC, Esther CR Jr, et al. Lung transplant outcomes in cystic fibrosis patients with pre-operative Mycobacterium abscessus respiratory infections. Clin Transplant 2013; 27:523.
  153. Boyle MP. Update on maintaining bone health in cystic fibrosis. Curr Opin Pulm Med 2006; 12:453.
  154. The International Society for Heart and Lung Transplantation. Heart/Lung Registries. http://www.ishlt.org/registries/slides.asp?slides=heartLungRegistry (Accessed on May 01, 2016).
  155. Vos R, Verleden GM, Dupont LJ. Long-term survival after lung transplantation among cystic fibrosis patients: Moving away from mere palliation. J Heart Lung Transplant 2016; 35:837.
  156. Stephenson AL, Sykes J, Berthiaume Y, et al. Clinical and demographic factors associated with post-lung transplantation survival in individuals with cystic fibrosis. J Heart Lung Transplant 2015; 34:1139.
  157. Liou TG, Adler FR, Cox DR, Cahill BC. Lung transplantation and survival in children with cystic fibrosis. N Engl J Med 2007; 357:2143.
  158. Aurora P, Whitehead B, Wade A, et al. Lung transplantation and life extension in children with cystic fibrosis. Lancet 1999; 354:1591.
  159. Smeritschnig B, Jaksch P, Kocher A, et al. Quality of life after lung transplantation: a cross-sectional study. J Heart Lung Transplant 2005; 24:474.
  160. Kugler C, Fischer S, Gottlieb J, et al. Health-related quality of life in two hundred-eighty lung transplant recipients. J Heart Lung Transplant 2005; 24:2262.
  161. Nixon PA, Morris KA. Quality of life in pediatric heart, heart-lung, and lung transplant recipients. Int J Sports Med 2000; 21 Suppl 2:S109.
  162. Patel EM, Swamy GK, Heine RP, et al. Medical and obstetric complications among pregnant women with cystic fibrosis. Am J Obstet Gynecol 2015; 212:98.e1.
  163. Thorpe-Beeston JG, Madge S, Gyi K, et al. The outcome of pregnancies in women with cystic fibrosis--single centre experience 1998-2011. BJOG 2013; 120:354.
  164. Cheng EY, Goss CH, McKone EF, et al. Aggressive prenatal care results in successful fetal outcomes in CF women. J Cyst Fibros 2006; 5:85.
  165. Tonelli MR, Aitken ML. Pregnancy in cystic fibrosis. Curr Opin Pulm Med 2007; 13:537.
  166. Ahluwalia M, Hoag JB, Hadeh A, et al. Cystic fibrosis and pregnancy in the modern era: a case control study. J Cyst Fibros 2014; 13:69.
  167. Schechter MS, Quittner AL, Konstan MW, et al. Long-term effects of pregnancy and motherhood on disease outcomes of women with cystic fibrosis. Ann Am Thorac Soc 2013; 10:213.
  168. Canny GJ. Pregnancy in patients with cystic fibrosis. CMAJ 1993; 149:805.
  169. Flume PA, Strange C, Ye X, et al. Pneumothorax in cystic fibrosis. Chest 2005; 128:720.
  170. Flume PA, Yankaskas JR, Ebeling M, et al. Massive hemoptysis in cystic fibrosis. Chest 2005; 128:729.
  171. Flume PA. Pneumothorax in cystic fibrosis. Curr Opin Pulm Med 2011; 17:220.
  172. Flume PA, Mogayzel PJ Jr, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: pulmonary complications: hemoptysis and pneumothorax. Am J Respir Crit Care Med 2010; 182:298.
  173. Dusmet M, Winton TL, Kesten S, Maurer J. Previous intrapleural procedures do not adversely affect lung transplantation. J Heart Lung Transplant 1996; 15:249.
  174. Curtis HJ, Bourke SJ, Dark JH, Corris PA. Lung transplantation outcome in cystic fibrosis patients with previous pneumothorax. J Heart Lung Transplant 2005; 24:865.
  175. Noppen M, Dhondt E, Mahler T, et al. Successful management of recurrent pneumothorax in cystic fibrosis by localized apical thoracoscopic talc poudrage. Chest 1994; 106:262.
  176. Schechter MS, Fink AK, Homa K, Goss CH. The Cystic Fibrosis Foundation Patient Registry as a tool for use in quality improvement. BMJ Qual Saf 2014; 23 Suppl 1:i9.
  177. Mogayzel PJ Jr, Dunitz J, Marrow LC, Hazle LA. Improving chronic care delivery and outcomes: the impact of the cystic fibrosis Care Center Network. BMJ Qual Saf 2014; 23 Suppl 1:i3.