Patients with sickle cell disease frequently develop respiratory illnesses, including infections, asthma, and acute chest syndrome (ACS), a complication of the disease and a leading cause of death. ACS is linked to a number of conditions, including pulmonary infection, pulmonary infarction resulting from microvascular occlusion by sickled red cells or thromboembolism, or pulmonary fat embolism with inflammation. Atypical bacteria and viral infections account for over 50 percent of respiratory infections associated with ACS.
While there have been a number of questionnaires developed to identify viral upper respiratory infections for clinical studies, data on the validation of these questionnaires are limited, particularly in children. According to Meyer Kattan, MD, Director of the Pediatric Pulmonary Division at NewYork-Presbyterian/Morgan Stanley Children's Hospital, no questionnaires, to their knowledge, have been used and validated for children with sickle cell disease. Such a tool could be very helpful in clinical trials and epidemiologic studies.
Dr. Aliva De
While taking part in the ViDAS1 trial to evaluate the use of vitamin D in reducing respiratory complications in children and adolescents with sickle cell disease, Dr. Kattan and pediatric pulmonologist Aliva De, MD, decided it would be beneficial to develop a respiratory symptoms questionnaire to screen and track respiratory events, including respiratory infections, asthma exacerbations, and ACS. Partnering with Margaret T. Lee, MD, and Gary M. Brittenham, MD, in the Division of Pediatric Hematology/Oncology/Stem Cell Transplantation at NewYork-Presbyterian Morgan Stanley Children’s Hospital, the team sought to create a useful and efficient questionnaire to determine the annual rates of respiratory events. The questionnaire would be administered biweekly over a two-year period.
Children and adolescents were recruited from the Pediatric Sickle Cell Program at NewYork-Presbyterian/Columbia University Irving Medical Center. The questionnaire included six respiratory symptoms: difficulty breathing, wheezing, fever, cough, runny or stuffy nose, and sore throat. The results were then compared with the identification of viral respiratory pathogens from the patients’ nasal secretion samples by reverse transcriptase polymerase chain reaction (RT-PCR), a definitive test for confirming a viral upper respiratory infection.
Eighty questionnaire responses and nasal samples were collected from 53 children with sickle cell disease, ages 4 to 18 years. The questionnaire was administered over two seasons to encompass the full range of viruses that can vary by season. The questionnaire yielded a sensitivity of 82 percent and specificity of 72 percent with an overall accuracy of 76 percent. The kappa value was 0.53, indicating moderate agreement, and the Fleiss’ kappa test statistic was 4.77 with P<0.001, indicating that agreement between the two methods was not by chance.
The authors concluded that the respiratory questionnaire is a simple and valid tool for use in research studies related to sickle cell disease, including those evaluating interventions affecting respiratory outcomes. The questionnaire can also be a valuable resource when RT-PCR laboratory testing is not readily available.