“Understanding that CFRD contributes to morbidity and mortality in CF and that this can be tempered by aggressive screening and treatment of this condition has changed practice across the country and worldwide,” said coauthor Antoinette Moran, MD, division chief of pediatric endocrinology and diabetes at the University of Minnesota in Minneapolis, in an interview with Pulmonology Advisor. “Routine oral glucose tolerance test monitoring is recommended in all national and international CF guidelines, as is early institution of insulin therapy.”

Other Factors Influencing CF Severity


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In a study of 255 clinically stable patients with CF (aged 1 to 69 years), Muhlebach and colleagues found that the type of bacteria in sputum (n=200) or bronchoalveolar lavage (n=55) samples predicted a milder version of the disease.4 Of the patients who produced sputum samples, anaerobic bacteria occurred in patients with less severe disease and was associated with pancreatic sufficiency, better lung function, and better nutrition. However, individuals with Pseudomonas infections had worse nutrition and the F508del genotype.4

“This study showed that the subjects with CF who had a higher proportion of anaerobic bacteria to aerobic bacteria tended to be healthier when looking at lung function and nutritional status,” explained lead author and pediatric pulmonologist Marianne S. Muhlebach, MD, professor of pediatric pulmonology at the University of North Carolina, Chapel Hill. “An eradication strategy for anaerobic bacteria should not be attempted in patients who are somewhat older, ie, who are sputum producers as long as they are at their baseline. This should not be generalized to all patients with CF as the effect of anaerobic bacteria in younger [patients] may be different.”

Which Patients Should Receive Lung Transplantation?

CF is the primary indication for pediatric lung transplants,5 and for adults, it is the third most common reason, behind chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.6

“Knowing when to transplant CF patients can be very difficult,” said transplant pulmonologist Christopher S. King, MD, from the adult cystic fibrosis program at Inova Fairfax Hospital in Falls Church, Virginia, in an interview with Pulmonology Advisor. “A pattern of increasing hospitalizations for exacerbations, increasing multidrug resistance to colonizing organisms, and worsening pulmonary function generally indicates it is time to list a patient for transplant. Massive hemoptysis, pneumothorax, and development of pulmonary hypertension or significant hypercapnia are other possible indications. The biggest change in protocols is for urgent listing of CF patients with acute decompensation. In the past, these patients often were unsalvageable; however, with the advent of extracorporeal membrane oxygenation (ECMO) …many of these patients can be successfully bridged to transplantation with favorable outcomes.”

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Every patient with CF ≥12 years old on the lung transplant waiting list has an individualized lung allocation score (from 0-100), which is based on laboratory values, test results, and CF severity.7 The higher the score, the higher the priority for transplantation within a designated geographic area. Children <12 years old are given a priority 1 (urgent) or priority 2 status. Pediatric transplant candidates receive pediatric donor lungs ahead of adult candidates.7 Median survival rates for lung transplantation in pediatric and adult patients are 16.1 and 10.7 years, respectively.8

“CF patients who receive lung transplants enjoy the longest post-transplant survival among indicated diseases,” said Dr Quon.5 “Recent studies estimate approximately 50% of transplant recipients are alive after about 10 years. Post-transplant median survival vary country to country, but it ranges from approximately 8 to 10 years.”9

CF Centers Provide Comprehensive Care

Because CF is a multisystemic disease, patients need an interdisciplinary team of clinicians based at CF centers that provide comprehensive care. Patients with CF frequently experience bronchiectasis, exacerbations from chronic pulmonary infections, and pancreatic insufficiency.10

“These centers provide holistic care of the multiple organs involved in CF [and] can provide expertise with regards to the nuances of care including optimal antimicrobial regimens, airway clearance, and use of CFTR modulator therapy,” said Dr King. “In patients with respiratory failure, we want to ensure that clinicians do not give up on patients without considerations of advanced therapies like ECMO and transplantation.”

Summary and Clinical Applicability

Cystic fibrosis has no cure; however, lung transplantation can extend survival in patients with compromised lung function and increasing exacerbations. Many factors, including age at diagnosis, diabetes, and lung function, may predict outcomes.

Limitations and Disclosures

None.

References

  1. Desai S, Wong H, Sykes J, Stephenson AL, Singer J, Quon BS. Clinical characteristics and predictors of reduced survival for adult-diagnosed cystic fibrosis: analysis of the Canadian CF Registry [published online June 26, 2018]. Ann Am Thorac Soc. doi:10.1513/AnnalsATS.201801-037OC
  2. Farrell PM, White TB, Ren CL, et al. Diagnosis of cystic fibrosis: consensus guidelines from the Cystic Fibrosis Foundation. J Pediatr. 2017;181S:S4-S15. doi:10.1016/j.jpeds.2016.09.064
  3. Lewis C, Blackman SM, Nelson A, et al. Diabetes-related mortality in adults with cystic fibrosis. Role of genotype and sex. Am J Respir Crit Care Med. 2015;191(2):194-200.
  4. Muhlebach MS, Hatch JE, Einarsson GG, et al. Anaerobic bacteria cultured from cystic fibrosis airways correlate to milder disease: a multisite study [published July 11, 2018]. Eur Respir J. doi:10.1183/13993003.00242-2018.
  5. Goldfarb SB, Levvey BJ, Cherikh WS, et al. Registry of the International Society for Heart and Lung Transplantation: Twentieth Pediatric Lung and Heart-Lung Transplantation Report—2017; Focus Theme: Allograft ischemic time. J Heart Lung Transplant. 2017;36(10):1070-1079.
  6. National Heart, Lung, and Blood Institute. Lung transplant. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063063/. Accessed August 15, 2018.
  7. United Network for Organ Sharing. Questions and answers for transplant candidates about lung allocation. https://unos.org/wp-content/uploads/unos/Lung_Patient.pdf. Accessed August 15, 2018.
  8. Lund LH, Khush KK, Cherikh WS, et al, for the International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Heart Transplantation Report—2017; Focus Theme: Allograft ischemic time. J Heart Lung Transplant. 2017;36(10):1037-1046.
  9. 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(9):1139-1145.
  10. King CS, Brown AW, Aryal S, Ahmad K, Donaldson S. Critical care of the adult cystic fibrosis patient [published August 2, 2018]. CHEST. doi:10.1016/j.chest.2018.07.025