Dorothy hansine anderson described it first in 1938.
Ireland has most severe strains of CF ,incidence 3 times that of US and rest of EU.
Pancreas: failure to secrete digestive enzymes causing malabsorption, failure of growth and late development Men nearly always infertile – absence/atrophy of vas deferens Lifelong potentially fatal disease14% of all individuals with CF have CF-related diabetes. In individuals with CF over the age of 35 years, more than one quarter have CF-related diabetes due to duct obstruction leading to amyloid deposits. CF-related diabetes usually develops after the second decade of life and rarely before the age of 10 years, due to sparing of Langerhans cells. The incidence of diabetes requiring chronic insulin therapy in CF patients older than 13 years has been reported as 16.9%.
Increased requirement due to concurrent illness
The only way to cure CF would be to use gene therapy to replace the defective gene or to give the patient the normal form of the protein before symptoms cause permanent damage.
Transplantation Window of Opportunity—in an Ideal World In an idealized plot of the clinical course of disease over time, disease progression shows a clearly defined, inexorable, unremitting, downhill clinical course (click for animation). In this illustration (click), the “transplant window,” the critical period when transplantation would bring the most benefit, is clearly defined. Marshall SE, Kramer MR, Lewiston NJ, Starnes VA, Theodore J. Selection and evaluation of recipients for heart-lung and lung transplantation. Chest. 1990;98(6):1488-1494.
Transplantation Window of Opportunity—in Reality In reality, however, the clinical course of CF lung disease is anything but clearly defined (click for animation). All patients experience periods of deterioration followed by partial improvement. Thus, when it comes to the question of organ transplantation for CF patients in the real world, the transplantation window is not clearly defined. Furthermore, the longer the waiting list for organs, the harder it is to determine the window or the best time to have surgery.
Difficult Questions to Ask Before Organ Transplantation When should a patient be referred for evaluation? When should a patient be placed on the waiting list? When should a patient have a transplant?
The mean LAS for patients undergoing lung transplantation in Ireland was 44.7 (±3.1), and 35 (±0.4) for patients undergoing lung transplantation in the UK (p<0.05).
Consensus Guidelines for Referral of Lung Transplant Candidates with CF In 1998, an international consensus committee developed guidelines for the referral of CF patients for lung transplantation. Patients with FEV1 ≤30% of predicted and rapidly progressive respiratory deterioration (increasing number of hospitalizations, massive hemoptysis, recurrent pneumothorax, increasing cachexia, and rapid fall in FEV1) should be considered for lung transplantation. FEV1 status alone is not sufficient to warrant lung transplantation. Patients who are hypoxemic (PaO2 <7.3 kPa; 55 mm Hg) or hypercapnic (PaCO2 >6.7 kPa; 50 mm Hg) and are considered to have <50% chance of survival in 2 years should also be referred. Finally, early referral is recommended for young female patients who deteriorate rapidly and have a particularly poor prognosis, although current guidelines provide no objective method of identifying these individuals. These patients should be considered for transplantation on an individual basis. American Thoracic Society. International guidelines for the selection of lung transplant candidates. The American Society for Transplant Physicians (ASTP)/American Thoracic Society (ATS)/European Respiratory Society (ERS)/International Society for Heart and Lung Transplantation (ISHLT). Am J Respir Crit Care Med. 1998;158:335-339. Am J Respir Crit Care Med. Boehler A. Update on cystic fibrosis: selected aspects related to lung transplantation. Swiss Med Wkly. 2003;133:111-117.
Lung Transplantation in Adult CF Patients with History of Acute Respiratory Failure Mechanical ventilatory support was previously discouraged in CF patients because of poor outcomes. However, improved patient survival and the growth in lung transplantation have increased the indications for ICU care. In this study, Sood and colleagues researched documented the outcomes of 42 adults admitted to the ICU (at the University of North Carolina) from 1990 to 1998 for CF-related respiratory failure. Of these 42 patients, 37 required ventilatory support. (click for animation) More than half of the ICU patients died in ICU or within 6 months of discharge. (click) An additional 3 patients were alive 1 year after ICU discharge without lung transplantation. (click) 17 patients (40%) received lung transplants following ICU discharge (click) Of these, 14 patients (82% of transplant recipients) were alive 1 year post-transplant These results indicate that ICU care, including ventilatory support, is appropriate and effective for adults with reversible respiratory complications, particularly when lung transplant is imminent. Success with a strategy of mechanical ventilation followed by lung transplantation depends heavily on successfully procuring acceptable donor lungs in a timely manner. Thus, for many CF patients with end-stage disease, this strategy may not be feasible. Sood N, Paradowski LJ, Yankaskas JR. Outcomes of intensive care unit care in adults with cystic fibrosis. Am J Respir Crit Care Med. 2001;163:335-338.
Absolute Contraindications to Lung Transplantation Several conditions are absolute contraindications to lung transplantation, for example, major dysfunction of other organs, including cardiovascular disease, liver disease (eg, associated with hepatitis C infection), renal insufficiency (ClCr <50 mL/min), diabetes mellitus with end-organ damage, or other systemic disease that would compromise long-term survival. In addition, HIV, hepatitis B, or M tuberculosis infections cannot be cured and would compromise long-term survival; the decision to transplant patients previously treated for tuberculosis should be made on a case-by-case basis. Finally, lung transplantation is contraindicated in patients who have had active malignancy within the last 5 years. Cystic Fibrosis Foundation. Clinical Practice Guidelines for Cystic Fibrosis. 1997. American Thoracic Society. International guidelines for the selection of lung transplant candidates. The American Society for Transplant Physicians (ASTP)/American Thoracic Society (ATS)/European Respiratory Society (ERS)/International Society for Heart and Lung Transplantation (ISHLT). Am J Respir Crit Care Med. 1998;158:335-339. Am J Respir Crit Care Med.
Relative Contraindications to Lung Transplantation The following medical conditions may affect the long-term survival of lung transplant recipients. Patients with these conditions should be evaluated on a case-by-case basis. (click) Symptomatic osteoporosis: bone densitometry should be performed (click) CF-related arthropathy, which has been shown to negatively affect postoperative survival (click) Kyphoscoliosis, especially affecting the thorax (click) High-dose corticosteroid use: reduction of dose to ≤20 mg/d prednisone or prednisolone is recommended (click) Nutritional status <70% or >130% IBW: weight gain or loss is recommended for eligibility for transplantation (click) Substance addiction: use of alcohol, tobacco, or narcotics must be discontinued ≥6 months before referral for transplantation (click) Psychosocial problems: psychoaffective disorder, inability to comply with complex medical regimen, history of noncompliance (click) Invasive ventilation (click) Fungi or atypical mycobacteria: preoperative attempts at eradication with antimicrobial therapy is recommended (click) Pan-resistant organisms: synergy testing is recommended American Thoracic Society. International guidelines for the selection of lung transplant candidates. The American Society for Transplant Physicians (ASTP)/American Thoracic Society (ATS)/European Respiratory Society (ERS)/International Society for Heart and Lung Transplantation (ISHLT). Am J Respir Crit Care Med. 1998;158:335-339. Am J Respir Crit Care Med.
Survival of Transplant Recipients by Procedure Type Survival for all lung transplants and by procedure type is shown here for adult lung transplants performed between January 1990 and June 2002 and reported to the International Society for Heart & Lung Transplantation registry. For all patients, milestone survival rates were 84% at 3 months, 74% at 1 year, 58% at 3 years, 47% at 5 years, and 24% at 10 years.Mortality was highest in the first year post-transplant. Survival rates for single and bilateral lung transplants were comparable during the first post-transplant year but gradually diverged thereafter, showing a small advantage for bilateral recipients. However, single and bilateral recipients differ in age and indications for transplant; and because these factors were not considered in the survival analysis, it is difficult to conclude that a survival benefit is related to bilateral transplantation alone. Trulock EP, Edwards LB, Taylor DO, et al. The registry of the International Society for Heart and Lung Transplantation: twenty-first official adult lung and heart-lung transplant report. J Heart Lung Transplant. 2004;23:804-815.
Potential Surgical Complications of Lung Transplantation The most serious surgical complications of lung transplantation include primary graft failure caused by imperfect allograft preservation and ischemia-reperfusion injury or diffuse alveolar damage. The incidence of this complication ranges from 15% to 35%, and mortality rates associated with this complication can reach up to 60%. Vascular or airway anastomotic complication has an ~7% prevalence rate. The placement of a stent can correct this complication in most cases. Phrenic/vocal cord paresis may occur in 3%-30% of lung transplant recipients. No specific risk factors have been identified. Gastroparesis may occur in 25%-30% of lung and heart-lung transplant recipients. In severe cases, gastric bypass surgery may be warranted. Zuckerman JB, Kotloff RM. Lung transplantation for cystic fibrosis. Clin Chest Med. 1998;19:535-554. Trulock EP. Lung transplantation. Am J Respir Crit Care Med. 1997;155:789-818. Akindipe OA, Faul JL, Vierra MA, Triadafilopoulos G, Theodore J. The surgical management of severe gastroparesis in heart/lung transplant recipients. Chest. 2000;117(3):907-910.
Potential Medical Complications Following Lung Transplantation Obliterative bronchiolitis: Obstructive inflammation of the small airways develops in at least 50% of intermediate- and long-term survivors of lung transplantation. Acute rejection: Because donor lungs are matched only for blood type, rejection is more common and more severe than with other donor organs. Infection (viral, bacterial, fungal, protozoal): The use of immunosuppressive therapy reduces the ability to fight off infection. In addition, blunted cough reflex, bronchial anastomosis, or obliterative bronchiolitis can reduce mucociliary clearance and promote infection. Toxicity and side effects of immunosuppressives: nephrotoxicity, hypertension, hirsutism, and gingival hyperplasia Diabetes: Immunosuppressive agents may cause or worsen diabetes mellitus. Hyperlipidemia: Immunosuppressants may also increase cholesterol levels. Post-transplant lymphoproliferative disease (PTLD): Usually associated with Epstein-Barr virus infection of B cells brought on by immunosuppressive therapy; reduction or withdrawal of immunosuppressants is the typical treatment for PTLD, although the risk of graft rejection becomes an issue. Strokes and seizures: These complications are related to the immunosuppressive medications, especially cyclosporine and tacrolimus. Zuckerman JB, Kotloff RM. Lung transplantation for cystic fibrosis. Clin Chest Med. 1998;19:535-554. Kurland G, Orenstein DM. Complications of pediatric lung and heart-lung transplantation. Curr Opin Pediatr. 1994;6:262-271.
Causes of Death in Lung Transplant Recipients In the same study, causes of death among lung transplant recipients were analyzed according to time after transplantation. Early on, in the first post-transplant year, graft failure (red) and non-CMV infections (light blue) were the leading causes of death. These complications also contributed to deaths after 1 year, but to a lesser extent. Technical complications (dark blue) was an important cause of death within the first year only. Cardiovascular disease (orange) was a main cause of death within the first month. Later on, after the first year, approximately 30% of deaths were attributed to chronic rejection by bronchiolitis obliterans syndrome (purple); this was the single largest contributor to late mortality. Non-lymphoma malignancy (pink) became a more significant cause of death with time after transplantation. Figure adapted from Trulock EP, Edwards LB, Taylor DO, et al. The registry of the International Society for Heart and Lung Transplantation: twenty-first official adult lung and heart-lung transplant report. J Heart Lung Transplant. 2004;23:804-815, with permission from the International Society for Heart and Lung Transplantation.
“Woe to the child who tastes salty from a kiss on the brow, for he is cursed
and soon must die”.
Inherited disease that primarily affects the lungs and
digestive tract of about 1200 children and adults in
Cystic Fibrosis in Ireland
Most common life threatening genetically inherited disease.
Highest proportion of CF population in world.
Carriers of CF gene 1 in 19.
About 50 new cases diagnosed each year.
About 55% of CF patient population aged 18 or older.
Median age of survival 20’S.In 2011 28 patients died aged
between 13 and 54 yrs with average age at death of 23.5
Demographic data from
Number <18 yrs*
Number ≥18 yrs*
Mean age (yrs)*
Number males ≥18 yrs¥
Median age (yrs)*
Number females ≥18yrs¥ 235
Number diagnosed during year
Irish ethnicity* 1049
Number of males*
Deaths during year ∞
Number of females*
CFRI enrolees alive at the end of
Genetics: Mutations in gene on long arm of
chromosome 7 encoding for cystic fibrosis
trans-membrane conductance regulator
(CFTR) gene which encodes an epithelial
chloride channel .
Cystic fibrosis gene mutations
• Commonest mutation – Delta F508
UK and Ireland Caucasians - 75%
UK and Ireland Asians
• Common mutation found in 1 in 10 UK Asians - Y569D
(substitution G - T)
• Delta F508 and 28 others account for 85% mutations in the
Northern European Caucasian population
•Gland secretions thicker or more viscous than normal
•Small bowel: obstruction (meconium ileus in the
•Lungs : thick bronchial mucous, recurrent chest
infections, progressive lung damage, heart/lung
Viscid mucous secretion.
Decreased mucous clearance.
Bacterial trapping, proliferation and inflamation.
Chronic colonization of airway with microbes.
Bronchiectasis, cor pulmonale, death.
Nearly half of all patients with CF are infected with
harmful bacteria such as S.aureus and/or P.aerginosa
in their lungs.
Prevalance of A.fumigatus,S.maltophilia and MRSA
have increased in last few years.
S. aureus and H. influenza is more pravelent in
children with CF whereas P. aeruginosa, B.
cepacia complex and A. fumigatus is more
prevalent in adults with CF.
History and physical examination
History of cystic fibrosis in
Positive newborn screening test.
Sweat chloride levels
Concentration >60 mEq/l.
Documentation of dual CFTR
Median age at diagnosis in
months by symptom
Requirements may be difficult to meet as
CF Related DM.
High calorie diet
High Protein diet
Gene therapy is the use of
normal DNA to "correct" for
the damaged genes that
In the case of CF, gene
therapy involves inhaling a
spray that delivers normal
DNA to the lungs.
The goal is to replace the
defective CF gene in the
lungs to cure CF or slow the
progression of the disease.
•Lung transplant for advanced disease..
•Treating the symptoms does not cure the
disease, it can greatly improve the quality of
life for most patients and has, over the years,
increased the average life span of CF patients
to 40 years.
Total number of deaths and
median age at death of
Major or minor surgery.
Site of surgery.
Duration of surgery.
Emergency or elective procedure.
Not suitable for day case surgery usually.
Goal-Optimize patient as much as possible.
Continue regular medications, physiotherapy,
nebulized drugs as late as possible pre-op.
Chest radiograph, baseline ABG, bedside spirometry
Conduct of anaesthesia
Monitoring. Routine plus aterial line, CVC and cardiac
output monitoring depending on patient and type of
Regional or General anaesthesia.
Airway management LMA or oral ETT. Humidified gases
and low airway pressures.
TIVA or Volatile anaesthesia.
Limited use of NMB.
Goal –minimize development of postoperative
respiratory tract infection.
Good reversal of NMB,s.
HDU monitoring or ICU ventillation.
Lung transplant in cystic
The course of CF is very unpredictable, and that
makes the timing for transplant more difficult
About 1600 CF recipients since 1991
120-150 recipients each year
Third largest group to get transplanted
CF recipients do better in general than non-CF
Lung transplant and CF in
1991-2011-total number of lung transplants on Irish
patients 134.(102 in UK and 32 in Ireland)
Total lung transplants-Cystic fibrosis 52%,
Emphysema 15% and Idiopathic pulmonary fibrosis
Matter Lung transplants- 44% IPF, Emphysema 31%
and 16% cystic fibrosis.
of Opportunity—in an Ideal
Marshall SE, et al. Chest.
of Opportunity—in Reality
Difficult Questions to Ask
When should a patient be referred for evaluation?
When should a patient be placed on the waiting list?
When should a patient have a transplant?
Referral for Lung Transplant
Transplant team readiness and comfort level
Local transplant center culture
Wait times (less important now because of LAS)
Lung Allocation Score
New scoring system since May 2005
“How bad you need it + How well you’ll do with it”
Applies to transplant candidates > 12 yrs
Scores range from 0-100
Scores can be updated
Lung Allocation Score:
Height and Weight (BMI)
Use of supplemental
Six minute walk distance
Consensus Guidelines for Referral of
Lung Transplant Candidates with CF
FEV1 ≤30% of predicted with rapid, progressive
Increasing number of hospitalizations
Rapid fall in FEV1
Hypoxemia: PaO2 <7.3 kPa
Hypercapnia: PaCO2 >6.7 kPa
Early referral is recommended for young female
patients, who have particularly poor prognosis
American Thoracic Society. Am J Respir Crit Care Med. 1998.
Boehler A. Swiss Med Wkly. 2003.
Lung Transplantation in Adult CF Patients
with History of Acute Respiratory Failure
N = 42
Admitted to ICU with hypercapnic respiratory failure
n = 19 (45%)
Died in ICU
n = 17 (40%)
Received lung transplants
n = 14 (82%)
Alive at 1 year
n = 3 (7%)
Died within 6 months
of ICU discharge
n = 3 (7%)
Alive at 1 year
without lung transplant
Sood N, et al. Am J Respir Crit Care Med.
to Lung Transplantation
Active malignancy <5 years
Hepatitis B or C
Liver disease: hepatitis C
Renal failure: ClCr <50 mL/min
Other organ damage
Cystic Fibrosis Foundation. Clinical Practice Guidelines for Cystic Fibrosis. 1997.
American Thoracic Society. Am J Respir Crit Care Med. 1998.
Relative Contraindications to Lung
(<70% or >130% IBW)
American Thoracic Society. Am J Respir Crit Care Med. 1998.
Survival of Transplant Recipients by
Bilateral lung (N = 6686)
Single lung (N = 8581)
All lungs (N = 15,267)
Trulock EP, et al. J Heart Lung Transplant. 2004.
Potential Surgical Complications of
•Primary graft failure due to ischemiareperfusion injury/diffuse alveolar damage
•Anastomotic complications: vascular or
•Phrenic/vocal cord paresis
Zuckerman JB, et al. Clin Chest Med.
Trulock EP. Am J Respir Crit Care Med.
Akindipe OA, et al. Chest.
Causes of Death in Lung Transplant
Infection – Non-CMV
Malignancy – Non-lymphoma
Percent of deaths
31 days-1 year
Time after transplantation
Trulock EP, et al. J Heart Lung Transplant. 2004.
PROGNOSIS HAS IMPROVED,
BUT LIFE IS STILL SHORTER.