Cor Pulmonale in Cystic Fibrosis

 

 Buy Article Permissions and Reprints

ABSTRACT

Cystic fibrosis is a common autosomal recessive disorder that is associated with a defective chloride transport channel in epithelial cells. The discovery of the cystic fibrosis gene in 1989 has led to a better understanding of the pathophysiology of the disease and the development of more effective therapeutic interventions. Chronic recurrent lung infections, pancreatic exocrine insufficiency, and elevated sweat chloride levels are hallmarks of the disease. Survival of patients with cystic fibrosis is steadily improving and most patients survive into adulthood. As lung disease progresses, secondary pulmonary hypertension and cor pulmonale are likely to develop. Pulmonary hypertension is correlated with the degree of hypoxemia and may be associated with increased mortality. The goal of therapy of cor pulmonale in cystic fibrosis is to correct hypoxemia and lower the elevated pulmonary artery pressures. This is best achieved by supplemental oxygen and aggressive treatment of the pulmonary disease with antibiotics and airway clearance techniques. It is also important to assess oxygenation during sleep and exercise. Bilateral lung transplantation is a treatment option for patients with end-stage lung disease, even in the presence of cor pulmonale.

REFERENCES

• 1 Kosork M R, Wei W H, Farrell P M. The incidence of cystic fibrosis.  Stat Med . 1996;  15 449-462
  CrossrefPubMedGoogle Scholar
• 2 Cystic Fibrosis Foundation. Patient Registry 2000 Annual Report. Bethesda, MD: Cystic Fibrosis Foundation; 2001
• 3 Yankaskas J R, Knowles M R. Cystic Fibrosis in Adults. Philadelphia: Lippincott-Raven 1999: 45-67
  Google Scholar
• 4 Cystic Fibrosis Foundation. Clinical Practice Guidelines for Cystic Fibrosis Washington, DC: Cystic Fibrosis Foundation; 1997
• 5 Riordan J R, Rommens J M, Kerem B. et al . Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.  Science . 1989;  245 1066-1073
  CrossrefPubMedGoogle Scholar
• 6 Kerem E, Corey M, Kerem B S. et al . The relationship between genotype and phenotype in cystic fibrosis: analysis of the most common mutation (ΔF508).  N Engl J Med . 1990;  323 1517-1522
  PubMedGoogle Scholar
• 7 Stern R C. The diagnosis of cystic fibrosis.  N Engl J Med . 1997;  336 487-491
  CrossrefPubMedGoogle Scholar
• 8 Welsh M J, Anderson M P, Rich D P. et al .Cystic fibrosis, CFTR, and abnormal electrolyte transport. In: Davis PB, ed. Cystic Fibrosis New York: Marcel Dekker 1993: 29-52
  Google Scholar
• 9 Cutting G R. Genotype defect: its effect on cellular function and phenotypic expression.  Sem Respir Crit Care Med . 1994;  15 356
  PubMedGoogle Scholar
• 10 Seeger W, Suttorp N. Role of membrane lipids in the pulmonary vascular abnormalities caused by bacterial toxins.  Am Rev Respir Dis . 1987;  136 462-466
  PubMedGoogle Scholar
• 11 Stern R. Inpatient treatment of cystic fibrosis pulmonary disease. In: Orenstein DM, Stern RC, eds. Treatment of the Hospitalized Cystic Fibrosis Patient New York: Marcell Dekker 1998: 79-133
  Google Scholar
• 12 Ramsey B W. Management of pulmonary disease in patients with cystic fibrosis.  N Engl J Med . 1996;  335 179-188
  CrossrefPubMedGoogle Scholar
• 13 Royce S W. Cor pulmonale in infancy and early childhood: report on 34 patients, with special reference to the occurrence of pulmonary heart disease in cystic fibrosis of the pancreas.  Pediatrics . 1951;  8 255-274
  PubMedGoogle Scholar
• 14 Stern R C, Borkat G, Hirschfeld S S. et al . Heart failure in cystic fibrosis: treatment and prognosis of cor pulmonale with failure of the right side of the heart.  Am J Dis Child . 1980;  134 267-272
  PubMedGoogle Scholar
• 15 Levesque P C, Padraig J H, Hume J R, Kenyon J L, Horowitz B. Expression of cystic fibrosis transmembrane regulator Cl-channels in heart.  Circ Res . 1992;  711 1002-1007
  PubMedGoogle Scholar
• 16 Hart P, Warth J D, Leresque P C. et al . Cystic fibrosis gene encodes a cAMP-dependent chloride channel in heart.  Proceedings of the National Academy of Sciences of the United States of America . 1996;  93 6343-6348
  CrossrefPubMedGoogle Scholar
• 17 Goldring R M, Fishman A P, Turino G M, Cohen H I, Denning C R, Andersen D H. Pulmonary hypertension and cor pulmonale in cystic fibrosis of the pancreas.  J Pediatrics . 1964;  65 501-524
  PubMedGoogle Scholar
• 18 Symchych P S. Pulmonary hypertension in cystic fibrosis.  Arch Pathol . 1971;  91 409-414
  PubMedGoogle Scholar
• 19 Fraser K L, Tullis D E, Sasson Z, Hyland R H, Thornley K S, Hanly P J. Pulmonary hypertension and cardiac function in adult cystic fibrosis: role of hypoxemia.  Chest . 1999;  115 1321-1328
  CrossrefPubMedGoogle Scholar
• 20 Viles P J, Shepherd J T. Relationship between pH, pO₂ and pCO₂ on the pulmonary vascular bed of the cat.  Am J Physiol . 1968;  215 1170-1176
  PubMedGoogle Scholar
• 21 Enson Y, Giuntini C, Lewis M L. et al . The influence of hydrogen ion concentration and hypoxia on the pulmonary circulation.  J Clin Invest . 1964;  43 1146
  PubMedGoogle Scholar
• 22 Jessup M, Sutton S G, Weber K. et al . The effect of chronic pulmonary hypertension on left ventricular size, function, and interventricular septal motion.  Am Heart J . 1987;  113 1114-1122
  CrossrefPubMedGoogle Scholar
• 23 Jacobstein M D, Hirschfeld S S, Winnie G, Doershuk C, Liebman J. Ventricular interdependence in severe cystic fibrosis.  Chest . 1981;  80 399-404
  PubMedGoogle Scholar
• 24 Vizza C D, Lynch J P, Ochoa L L, Richardson G, Trulock E P. Right and left ventricular dysfunction in patients with severe pulmonary disease.  Chest . 1998;  113 576-583
  CrossrefPubMedGoogle Scholar
• 25 Hortop J, Desmond K J, Coates A L. The mechanical effects of expiratory airflow limitation on cardiac performance in cystic fibrosis.  Am Rev Respir Dis . 1988;  137 132-137
  PubMedGoogle Scholar
• 26 Moss A J. The cardiovascular system in cystic fibrosis.  Pediatrics . 1982;  70 728-741
  PubMedGoogle Scholar
• 27 Fowler R S, Rappaport H, Cunningham K, Crozier D N, Levison H, Rowe R D. Cor pulmonale in cystic fibrosis.  J Electrocardiology . 1981;  14 319-324
  PubMedGoogle Scholar
• 28 Gewitz M, Eshaghpour E, Holsclaw D S, et.al. Echocardiography in cystic fibrosis.  Am J Dis Child . 1977;  131 275-280
  PubMedGoogle Scholar
• 29 Ionescu A A, Ionescu A, Payne N, Obieta-Fresnedo I, Fraser A G, Shale D J. Subclinical right ventricular dysfunction in cystic fibrosis.  Am J Respir Crit Care Med . 2001;  163 1212-1218
  PubMedGoogle Scholar
• 30 Rosenthal A, Tucker C R, Williams R G, Khaw K T, Strieder D, Schwachman H. Echocardiographic assessment of cor pulmonale in cystic fibrosis.  Pediatr Clin North Am . 1976;  23 327-344
  PubMedGoogle Scholar
• 31 Ryssing E. Assessment of cor pulmonale in cystic fibrosis by echocardiography.  Acta Pediatr Scand . 1977;  66 753-756
  PubMedGoogle Scholar
• 32 Panidis I P, Ren J F, Holsclaw D S, Kotler M N, Mintz G S, Ross J. Cardiac function in patients with cystic fibrosis: evaluation by two-dimensional and Doppler echocardiography.  J Am Coll Cardiol . 1985;  6 701-706
  PubMedGoogle Scholar
• 33 Piepsz A, Ham H R, Millet E, Dab I. Determination of right ventricular ejection fraction in children with cystic fibrosis.  Pediatr Pulmonol . 1987;  3 24-28
  PubMedGoogle Scholar
• 34 Florea V G, Florea N D, Sharma R. et al . Right ventricular dysfunction in adult severe cystic fibrosis.  Chest . 2000;  118 1063-1068
  CrossrefPubMedGoogle Scholar
• 35 Ramsey B W, Pepe M S, Quan J N. et al . Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group.  N Engl J Med . 1999;  340 23-30
  CrossrefPubMedGoogle Scholar
• 36 Fuchs J F, Borowitz D S, Christiansen D H. et al . Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis.  N Engl J Med . 1994;  331 637-642
  CrossrefPubMedGoogle Scholar
• 37 Konstan M W, Byard P J, Hoppel C L. et al . Effect of high-dose ibuprofen in patients with cystic fibrosis.  N Engl J Med . 1995;  332 848-854
  CrossrefPubMedGoogle Scholar
• 38 Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial.  Ann Intern Med . 1980;  93 391-398
  PubMedGoogle Scholar
• 39 Bradley T D, Rutherford R, Gorssman R F. et al . Role of daytime hypoxemia in the pathogenesis of right heart failure in the obstructive sleep apnea syndrome.  Am Rev Respir Dis . 1985;  131 835-839
  PubMedGoogle Scholar
• 40 Stokes D C, McBride J T, Wall M A, Erba G, Strieder D J. Sleep hypoxemia in young adults with cystic fibrosis.  Am J Dis Child . 1980;  134 741-743
  PubMedGoogle Scholar
• 41 Coffey M J, FitzGerald M X, McNicholas W T. Comparison of oxygen desaturation during sleep and exercise in patients with cystic fibrosis.  Chest . 1991;  100 659-662
  PubMedGoogle Scholar
• 42 Tepper R S, Skatrud J B, Dempsey J A. Ventilation and oxygenation changes during sleep in cystic fibrosis.  Chest . 1983;  84 388-393
  PubMedGoogle Scholar
• 43 Becker H F, Piper A J, Flynn W E. et al . Breathing during sleep in patients with nocturnal desaturation.  Am J Respir Crit Care Med . 1999;  159 112-118
  CrossrefPubMedGoogle Scholar
• 44 Frangolis D D, Despina D, Wilcox P G. Predictability of oxygen desaturation during sleep in patients with cystic fibrosis: clinical, spirometric, and exercise parameters.  Chest . 2001;  119 434-441
  CrossrefPubMedGoogle Scholar
• 45 Villa M P, Pagani J, Lucidi V, Plamides S, Ronchetti R. Nocturnal oximetry in infants with cystic fibrosis.  Arch Dis Child . 2001;  84 50-54
  CrossrefPubMedGoogle Scholar
• 46 Nixon P A, Orenstein D M, Curtis S E, Ross E A. Oxygen supplementation during exercise in cystic fibrosis.  Am Rev Respir Dis . 1990;  142 807-811
  PubMedGoogle Scholar
• 47 Versteegh F GA, Borgarrd J M, Raatgever J W, Stam H, Neijens J F, Kerrebijn K F. Relationship between airway obstruction, desaturation during exercise and nocturnal hypoxaemia in cystic fibrosis patients.  Eur Respir J . 1990;  3 68-73
  PubMedGoogle Scholar
• 48 Nixon P, Orenstein D, Kelsey S, Doershuk C. The prognostic value of exercise testing in patients with cystic fibrosis.  N Engl J Med . 1992;  327 1785-1788
  Google Scholar
• 49 Zinman R, Corey M, Coates A L. et al . Nocturnal home oxygen in the treatment of hypoxemic cystic fibrosis patients.  J Ped . 1989;  114 368-377
  PubMedGoogle Scholar
• 50 Dinwiddie R, Madge S, Prasad S A, Balfour-Lynn I M. Oxygen therapy for cystic fibrosis.  J R Soc Med . 1999;  92 (suppl 37) S19-S22
  PubMedGoogle Scholar
• 51 Geggel R L, Dozor A J, Flyler D C, Reid L M. Effect of vasodilators at rest and during exercise in young adults with cystic fibrosis and chronic cor pulmonale.  Am Rev Respir Dis . 1985;  131 531-536
  PubMedGoogle Scholar
• 52 Michael J R, Kennedy T P, Fitzpatrick S, Rosenstein B J. Nifedipine inhibits hypoxic pulmonary vasoconstriction during rest and exercise in patients with cystic fibrosis and cor pulmonale.  Am Rev Respir Dis . 1984;  130 516-519
  PubMedGoogle Scholar
• 53 Yankaskas J R, Mallory G B. Lung transplantation in cystic fibrosis: consensus conference statement.  Chest . 1998;  113 217-226
  CrossrefPubMedGoogle Scholar
• 54 Yacoub M H, Banner N R, Khaghani A. et al . Heart-lung transplantation for cystic fibrosis and subsequent domino heart transplantation.  J Heart Transplant . 1990;  9 459
  PubMedGoogle Scholar