Low forced expiratory volume is associated with earlier death in sickle cell anemia.
Pulmonary complications result in mortality in adults with sickle cell anemia (SCA). We tested the hypothesis that abnormal pulmonary function was associated with earlier death. A prospective cohort of adults with SCA, followed in the Cooperative Study for Sickle Cell Disease, was constructed using the first pulmonary function test at >21 years of age. Spirometry measures: forced expiratory volume in 1 second (FEV1), forced vital capacity, and total lung capacity were categorized based on age, gender, height, and race. Pulmonary function patterns were categorized based on the American Thoracic Society guidelines using both spirometry and lung volumes. A cohort of 430 adults with SCA, mean age 32.6 ± 9.5 (range, 21.0-67.8) years at time of first pulmonary function test, and a median follow-up of 5.5 years, was evaluated. A total of 63 deaths occurred. At baseline, 47% had normal, 29% restrictive, 8% obstructive, 2% mixed, and 14% nonspecific lung function patterns. In the final multivariable model, lower FEV1 percent predicted was associated with increased hazard ratio of death (HR per % predicted 1.02; 95% confidence interval [CI] 1.00-1.04; P = .037), as was older age (HR 1.07; 95% CI 1.04-1.10; P < .001), male sex (HR 2.09; 95% CI 1.20-3.65; P = .010), higher lactate dehydrogenase levels (HR per mg/dL 1.002; 95% CI 1.00-1.003; P = .015), and higher acute chest syndrome incidence rate (HR per event/year 10.4; 95% CI 3.11-34.8; P < .001). Presence of obstructive (HR 1.18; 95% CI: 0.44-3.20; P = .740) and restrictive (HR 1.31; 95% CI: 0.64-2.32; P = .557) pulmonary function patterns were not associated with earlier death. Understanding the pathophysiology of a low FEV1 percent predicted in individuals with SCA is warranted, enabling early intervention for those at risk.
Department of Medicine, Division of Hematology/Oncology, and Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease, Vanderbilt University School of Medicine, Nashville, TN;
Adetola A
AA
Kassim
National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA;
Amanda B
AB
Payne
Rodeghier Consultants, Chicago, IL;
Mark
M
Rodeghier
Massachusetts General Hospital and Harvard Medical School, Boston, MA;
Eric A
EA
Macklin
Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO; and.
Robert C
RC
Strunk
Department of Pediatrics and Medicine, Division of Hematology/Oncology, and Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease, Vanderbilt University School of Medicine, Nashville, TN.
Michael R
http://orcid.org/0000-0002-0574-1604
MR
DeBaun
D000328:Adult; D000367:Age Factors; D000368:Aged; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000401:mortality / Q000503:physiopathology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013147:Spirometry; D055815:Young Adult