Running h ead: ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE The Clinical Practice of Diagnosing Asthma in Children with Sickle Cell Disease Mikaela Harrington Laurie Duckworth, PhD, ARNP University of Florida College of Nursing
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 2 Abstract Children who suffer from sickle cell disease (SCD) are commonly admitted to the hospital for pulmonary related problems such as acute chest syndrome. The link between sickle cell disease and asthma as co morbidities has been discussed, yet many health care centers do not screen or diagnose c hildren with sickle cell disease for asthma. This paper explore s the way four academic health care centers screen and diagnose asthma in children with sickle cell disease and aims at uncovering the most effective methods amongst these institutions. Using I2B2, a de identified data repository, information about patients who had sickle cell disease, asthma diagnoses, and the development of acute chest syndrome was gathered for the institutions used in this study One institution had significantly better resu lts in comparison with the other three care centers, and this project aimed to uncover the methods that this specific institution used to screen and diagnose their SCD children with asthma. Questions were formulated in collaboration with UF pediatric hematologist and were posed to these institutions regarding the practices used in each center. Responses from the sites are currently pending.
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 3 The Clinical Practice of Diagnosing Asthma in Children with Sickle Cell Disease In patients with Sickle Cell Disease (SCD), a major cause of morbidity and mortality includes pulmonary complications. Acute Chest Syndrome (ACS) is the leading cause of premature death and is also the second most common reason for hospitalization in patient s with SCD (Miller, 2011). A lthough a sthma is common in children with SCD it remains underdiagnosed and poorly managed in this population. This problem is likely due to the difficulty in discerning asthma exacerbations from airway changes that are commonly seen in patients with SCD, such as shortness of breath, wheezing, and chest pain (DeBaun & Strunk, 2016). In a study that examined common reasons SCD children were referred to a pediatric respiratory clinic although only a small number o f patients were referred to the clinic due to suspected asthma and wheezing (~13%), 48% of all patients who were referred to the clinic for any reason w as discovered to have asthma ( Akthar et al., 2016). This study emphasize d the idea that asthma is often unrecognized and subsequently underdiagnosed in patients with SCD. A n asthma diagnosis in a patient with a co morbidity of SCD could ultimately lead to decreased hospital admissions for ACS and sickle cell crises During an asthma attack, bronchoconstricti on and altered ventilation perfusion can result in hypoxic areas, leading to decreased oxygen saturation and sickling in SCD children. These conditions are what ultimately predispose these SCD patients to developing ACS (Knight Madden et al., 2005). The m ain objective for this project is to find out what four academic medical centers are doing to diagnose their children who have SCD with asthma. Because there is a proven correlation of sickle cell disease and asthma, it is important to determine what can b e done for children with SCD who need an asthma diagnosis. This diagnosis can ultimately help children be prescribed the proper medication they need in order to prevent asthma attacks and possibly sickle
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 4 cell crises and incidences of acute chest syndrome. The results of this project will not only benefit the families and children with SCD who remain undiagnosed with asthma, but it may also help reduce the number of admissions in the hospital for respiratory related illnesses in sickle cell disease children. The findings may be able to help institutions across the United States implement new and efficient ways at diagnosing asthma in SCD children. This project is needed at this time because despite the literature about SCD, asthma, and ACS as co mo rbidities, asthma diagnoses in SCD patients remain low. The purpose of conducting this project is to compare the clinical practices of each of the four academic medical centers to find out what practices are effective and wh ich are ineffective. Many hospit als do not have a single protocol for diagnosing SCD patients with asthma, and therefore, many children and even adults, go undiagnosed for the remainder of their life. Currently at the University of Florida, the pediatric hematology clinic for children wi th SCD makes a referral for them to see a pulmonologist if asthma is suspected. However, these referrals seem to have an insignificant impact at improving asthma diagnoses rates at this institution as well as other institutions across the United States. I n fact, one study at J ohns Hopkins Hospital showed that out of seventy four pediatric patients who were referred to their pediatric pulmonary clinic after abnormal spirometry and/or positive asthma screening questionnaire, only 22% of those referred were a ctually seen in a pulmonary clinic (Sadreameli, Alade, Mogayzel, McGrath Morrow, & Strouse, 2017). Because asthma is a major risk factor for ACS, a diagnosis in children with SCD could possibly prevent a pain crisis or asthma exacerbation in these patients if they are properly medicated for the condition. A study by Boyd et al. (2006) reported that children with SCD and a clinical diagnosis of asthma had increased sickle cell related morbidity and had nearly twice as
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 5 many ACS episodes than patients without this diagnosis, confirming the association between asthma and ACS. The findings of the study also suggest that identifying and treating asthma in children with SCD may have an impact on decreasing SCD related morbidity (Boyd et al., 2006). C omparing the cu rrent practices of multiple academic health care centers and subsequently identifying their merits and faults can help determine if feasible and appropriate ways to screen and diagnose asthma in children with SCD exists. Asthma and SCD both occur more com monly in African Americans over any other race. In 2016, the Centers for Disease Control and Prevention (CDC) estimated that SCD affects 1 out of every 365 African American births and that African American children are 2 times more likely to have asthma th an White children. Despite these numbers, the likely potential for these two diagnoses as co morbidities remains understated. It is also important to note the differences between races when discussing asthma like symptoms. One study found that the differen ces in the words used by patients to describe their asthma like symptoms varied based on the race of the patient. African Americans suffering from airflow obstruction primarily used word descriptors pertaining to the upper airway, whereas Whites typically used lower airway and chest wall descriptors (Hardi e Janson Gold, Carrieri Kohlman, & Boushey 2000). Many physicians may be quick to dismiss a child that does not use the correct asthma in a child who needs it Many healthcare professionals screen patients for asthma by looking for key word descriptors meant to describe breathlessness; these descriptors include words describing shortness of breath, chest tightness, and wheezing (Hardie et al., 2000). However, these terms are culturally limiting. These word descriptors are how most White patients describe their asthma, rather than African Americans, despite the latter race being much more susceptible to asthma. This fact is significant, as many
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 6 children may go undiagnosed with asthma simply because of the word descriptors they use in describing their breathlessness. Physicians and other members of the healthcare team need to be ab le to provide culturally competent care to their patients and can help do so by understanding these differences between African American and White patients with regards to asthma management Other challenges with diagnosing SCD children with asthma involv es the high prevalence of wheezing and airway hyperresponsiveness that already occurs amongst patients with SCD. The significance of this lower airway obstruction that occurs in patients with SCD is not really understood, and because of these pulmonary com plications, many disagree about whether SCD is associated with a diagnosis of asthma (Cohen, Klings, & Strunk, 2015). Additionally, risk factors for ACS in children with SCD is similar to that of an asthma exacerbation and b oth conditions can present with pulmonary complications, including shortness of breath, coughing, wheezing, and pain upon breathing However, it is important to note that both asthma and ACS are two separate conditions needing two specific care strategies to properly manage a child wit h SCD who presents with pulmonary symptoms that mimic either condition (DeBaun & Strunk, 2016). This project began with existing data conducted by Dr. Laurie Duckworth, PhD, ARNP about the relationship between sickle cell disease, asthma, and acute chest syndrome at 4 academic medical centers (AMCs) These centers included: Harvard University, the University of Texas at Houston, Indiana University, and the University of Florida labeled A, B, C, and D, respectively The Electronic Medical Record (EMR) usin g i2b2, (a de identified data repository) for 4 AMCs was queried for the number of patients 5 34 years of age who were seen between 12/01/2010 and 12/01/2015 having co morbidities of Asthma, Sickle Cell Disease and Acute Chest Syndrome. The i2b2 query incl uded: (1) Number of patients with SCD (2) Number of
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 7 patients with SCD + Asthma, (3) Number of patients with SCD + ACS, and (4) Number of patients with SCD + ACS + Asthma. The combined total number of patients for each category we re as follows, respectively; (1) 2749, (2) 577, (3) 409, and (4) 249. The project began with the results of the data from i2b2. Results from academic medical center C, Indiana University, was si gnificant in proving the correlation between sickle cell disease, asthma, and acute chest syndrome. Indiana was found to have a significantly highe r percentage of asthma diagnoses amongst their SCD population over every other institution tested (See Append ix A) It was also found that nearly all SCD patients at Indiana who developed ACS during the specified period of the data query had a diagnosis of asthma, emphasizing the increased risk of developing ACS with an asthma co morbidity (see Appendix B). This data also suggests that asthma may be more common amongst patients with SCD than with those without it If Indiana University has a unique way at diagnosing their SCD children with asthma and it is deemed effective and practical, then the University of Florida, University of Texas, and Harvard University can all implement this new practice in their pediatric hematology/pulmonology clinics. Other institutions across the U.S. can also use the findi ngs of this study to improve the rate at which they diagnose SCD children with asthma. Throughout this project, communication went back and forth between the pediatric hematologist s of each medical institution. After gathering the results of the data coll ection of the Although no responses have been received yet, part of t his project focused on developing and curating the questions that needed to be asked to each institution to gather the necessary
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 8 information. Questions were created and then redrafted before being sent to each site. The original six questions a re as follow s: 1. How do you define asthma ? Is it usually p hysician diagnosed or per parent report? 2. How do you define acute chest syndrome? 3. How is asthma managed in your clinic? 5. Do your patients receive a pulmonary referral? 6. Do you screen for asthma in your clinic? helped alter the questions to make them more focused. The finalized questions that were se nt to the sites are as follows: 1. Does your sickle cell team use a standardized definition for asthma diagnosis? 2. Does your sickle cell team use a standardized definition for the diagnosis of acute chest syndrome? 3. How would you describe your patient populatio therapy? 4. Do you perform screening pulmonary function tests in your pediatric patients with asthma? If so, how often or at what age? 5. Do you perform pulmonary function testing on all children with sickle cell disease who ha ve a suspected asthma diagnosis? 6. Do you routinely screen for asthma in your sickle cell clinic? If yes, how do you screen patients (e.g. history, screening questionnaires, PFTs) ?
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 9 The definition of asthma may vary amongst institutions and may affect asthma diagnosis rates in children with SCD For this reason, the questions that were drafted for each academic while also questioning asthma screening practices and man agement in their SCD patients. Some clinicians define asthma as a personal or parenteral report of a physician diagnosis of the condition (Subramanian & Kennedy, 2009). Others define asthma simply as the report of a medical history that includes wheezing a nd other asthma like symptoms (Arteta et al., 2014). The definition of acute chest syndrome may vary as well, with some definitions requiring different symptoms to be present than others. Vichinsky et al. (2000) defines acute chest syndrome as having a new pulmonary infiltrate on a chest x ray with chest pain, tachypnea, or wheezing. Another definition of acute chest syndrome requires having chest pain with a fever, pulmonary infiltrates, and an increased number of leukocytes (Charache, Scott & Charache, 1 979). Patient adherence rates to asthma therapy is also essential information to find out from each site. Ultimately, if a child is diagnosed with asthma but does not adhere to their medication regimen, then their risk for developing acute chest syndrome due to pulmonary complications markedly increases. In one study that followed 93 children with SCD and their adherence to daily medications, which included asthma medications, it was found that the adherence rate for all asthma medications prescribed to ch ildren with SCD who had asthma was only 59.3% (Patel, Lindsey, Strunk, & DeBaun, 2010). These results show that even if an asthma diagnosis exists in a SCD patient, they may not adhere to the medication and may cause complications leading to ACS.
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 10 The ne xt two questions seek to find out if the pediatric SCD patients from each medical center have a pulmonary function test (PFT) done once they are suspected of having asthma or if there is another way that each site goes about diagnosing their patients. As p reviously mentioned, an asthma diagnosis. Because of this, many children may go their whole life without ever having pulmonary function tests done, which are univer sally viewed as the most accurate indicator of asthma. If all children with SCD who are seen at their hematology clinic are ultimately given PFTs during their visit to screen for asthma, then the rate of asthma diagnoses in this population would, predictab ly, increase. The last question that was asked to each site focuses on the different methods that healthcare centers may possibly use to screen their patients for asthma. As previously mentioned, some healthcare professionals consider a diagnosis of asthm a to be based on physician discretion, whereas others emphasize the need for a pulmonary function test (PFT) to be done before a diagnosis of asthma should be made. Screening questionnaires are another useful tool that clinicians can use to screen SCD chil dren for asthma to determine if a diagnosis should or should not be made. If it is found that multiple sites do use screening questionnaires as part of their clinical practice, then asthma screenings and diagnoses that were able to be obtained due to these questionnaires should be explored. It is also important to determine and compare the questions and word descriptors used by each site who does use a screening questionnaire By doing so, one may be able to determine if different words or questions can hel p assess a child with SCD for asthma better than others. Some clinics and hospitals choose to use screening questionnaires to help screen a child for asthma. Many studies have shown how these asthma screening questionnaires can ultimately
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 11 help lead to a d iagnosis of asthma in children with sickle cell disease. One study, where 41 out of 51 eligible participants completed an asthma screening questionnaire as well as spirometry, had over half of the participants (51.2%) demonstrate evidence of airway obstruc tion. It was also found that baseline demographics, previous respiratory complications, and complete blood counts did not have a significant difference in the findings between the obstructive and nonobstructive groups (Yadav, et al., 2015). In this study, 13 children received a physician diagnosis of asthma, and out of these 13, 11 were placed on asthma controlling medications after being evaluated by pulmonologists. This study was one of many that emphasized the importance of screening tools for SCD childr en, and how it could possibly lead to an asthma diagnosis and a subsequent medication regimen for the disease. At the present time, there has been no response back to these questions The main barrier to this project has been waiting for the responses from each academic medical center Without these responses, the study can not move forward because the clinical practices of the sites are unknown Although questions were sent out in January of 2018, no replies have been received yet. Follow up emails were sent out, but at the time of this being written, there are still no answers. The project was originally set to be a conference call between the centers, but because of the difficulty in scheduling a time that would work for all the institutions, it was de cided that email would be the best way to communicate with the centers. Even so, communication s between the pediatric hematologists ha ve proven to be more difficult than originally anticipated. In the meantime, state demographics of each academic medical center were explored. The purpose of exploring this data was to determine if there were any significant trends in thes e states that each academic medical center resides in based on the African American population and number of asthma diagno ses. Because Afr ican Americans have a much greater chance at having
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 12 asthma than any other race it was assumed that the states with a higher percentage of African Americans would also have higher percentages of asthma diagnoses Exploring state demographics was also helpf ul in determin ing if environmental or racial influences played a significant role in the results of the data set. According to State Data Profiles published by the CDC, the prevalence of asthma in children 0 17 years of age living in Florida in 2007 was 8.3% compared to the U.S. rate of 9.0% In 2008, the prevalence of asthma in Texas, Indiana, and Massachusetts of children 0 17 years of age were as follows, respectively: 9.2%, 8.6%, and 9.8% (Centers for Disease Control and Preven tion, 2011). Additionally, the 2010 Census reported the African American population for Florida, Texas, Indiana, and Massachusetts in respect to their overall populations were as follows, respectively: 21.3%, 16.8%, 10.8%, and 8.2% (U.S. Census Bureau, 201 0). These percentages show all the states that each academic medical center resides in have similar asthma prevalence rates for their children. However, Florida and Texas have a significantly higher percentage of African Americans in their population in c omparison to both Indiana and Massachusetts. While one would assume that this might signify a greater number of asthma diagnoses for these states, there was not a significant difference in the percentages of children with asthma between the four states It is also important to note that the University of Texas and the University of Florida, Academic Medical Centers B and D, respectively, had the two lowest rates of asthma diagnoses in their children with SCD compared to the other two medical centers (See Ap pendix A). Having the two lowest rates of asthma diagnoses implies that individual clinical practices by each site play a crucial role in how these children are being screened and diagnosed for asthma.
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 13 Additionally, it was surprising to not e that Indiana University had the highest rates of asthma diagnoses in their children with SCD when the state of Indiana had the lowest percentage of asthma diagnoses and second lowest percentage of African Americans residing in that state compared to the other three sta tes These results imply that the data results of the academic medical centers are probably not influenced by environmental or racial factors. Rather, it highlights the idea that Indiana University is doing something unique with their clinical practice of diagnosing children with SCD with asthma. Conclusions The goal of this project was to uncover the most effective clinical practice at diagnosing asthma in children with SCD by examining the current practices of four academic medical centers. Although the re have been no official results from the project, the link between SCD, asthma, and ACS in pediatric patients has been established The correlation between these co morbidities highlights the need and importance for new and inventive ways to address undia gnosed asthma in children with SCD. While the University of Florida currently refers their pediatric SCD patients to a pulmonary clinic, the number of asthma diagnoses in this p opulation is unpromising and suggest s that many patients never receive any sort of pulmonary screening or pulmonary function test. Although pediatric SCD patients are being referred to be seen by a pulmonologist, it is highly unlikely that they are ever seen in a clinic. Th us these children remain undiagnosed with asthma. Because th e data from Indiana University was so promising, their clinical practice s of diagnosing their SCD children with asthma, once uncovered, may ultimately be able to help shape the way for other healthcare institutions to improve their own asthma diagnosis rat es in this population.
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 14 While are unknown at this time, there remains s peculation about what could be. Possibly, but unlikely, Indiana University could have a pulmonologist directly in the pediatric hematolog y clinic that tests sickle cell disease children for asthma while they are already at the hospital. This would erase the referral aspect of the practice that many other institutions use for their patients with suspected asthma. While this practice would ex unlikely that a hospital would have a pulmonologist working on call for hematology. Perhaps the pulmonology and hematology clinics are near each other and patients could simpl y see both doctors the same day, rather than having to make an appointment and a subsequent trip to the hospital to get tested for asthma. Throughout this project, I have learned the difficulty in collaborating with stakeholders and the great amount of time it takes to gather the necessary data and research. Any further research endeavors I partake in, I would probably start communications between stakeholders at an earlier time to anticipate any potential barriers that may come about. Once the results o f this project clinical practices into the practices here at the University of Florida. Hopefully, any successful methods that are found to be used by the other medical centers are attainable, efficient, and cost effective so that they can be easily incorporated into practice at other medical centers The results, although not confirmed, look to be hopeful for SCD children who remain undiagnosed with asthma to receive the diagnosis and care they need to be able manage their disease effectively.
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 15 References Akthar M, Ruiz G, Chakravorty S, Bossley C, Rees D, Gupta A. (2016). P177 High prevalence of unrecognised asthma in children with sickle cell disease. Tho rax 16(71)179 181. Arteta, M., Campbell, A., Nouraie, M., Rana, S., Onyekwere, O. C., Ensing, G., ... Gordeuk, V. R. (2014). Abnormal pulmonary function and associated risk factors in children and adolescents with sickle cell anemia. Journal of Pediatr ic Hematology/Oncology 36 (3), 185 189. DOI: 10.1097/MPH.0000000000000011 Boyd, J.H., Macklin, E.A., Strunk, R.C., & DeBaun, M. R. (2006). Asthma is associated with acute chest syndrome and pain in children with sickle cell anemia. Blood 108(9), 2923 2927. https://doi.org/10.1182/blood 2006 01 011072. Centers for Disease Control and Prevention. (2016). Sickle Cell Disease. Retrieved from https://www.cdc.gov/nchs/fastats/older american health.html Centers for Disease Control and Prevention. (2011). State Data Profiles. Retrieved from https://www.cdc.gov/asthma/stateprofiles.htm Microbiology, treatment, and prevention. Arch Intern Med. 1979;139:67 69. Cohen RT, Klings ES, Strunk RC. Sickle cell disease: wheeze or asthma? Asthma Research and Practice 1(14). DeBaun M.R., Strunk R.C. (2016). The intersection between asthma and acute chest syndrome in children with sickle cell anaemia. Lancet, 387(2), 545. Hardie GE, Janson S, Gold WM, Carrieri Kohlman V, Boushey HA. (2000). Ethnic differences: word descriptors used by African American and white asthma patients during induced bronchoconstriction. Chest, 117, 935 943 Knight Madden J.M ., Forrester T.S., Lewis N.A., et al (2005). Asthma in children with sickle cell disease and its association with acute chest syndrome. Thorax 60, 206 210.
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ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 17 Appendix A 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0% A B C D Percentage of SCD Patients with Various Comorbidities Asthma ACS Asthma & ACS
ASTHMA IN CHILDREN WITH SICKLE CELL DISEASE 18 Appendix B Facility Asthma diagnosis No Asthma diagnosis OR p A ACS 37 (47%) 35 (10%) 7.9 <.001 no ACS 42 (53%) 314 (90%) B ACS 43 (75%) 35 (11%) 24.7 <.001 no ACS 14 (25%) 286 (89%) C ACS 144* (38%) 0* (0%) Inf <.001 no ACS 233 (62%) 825 (100%) D ACS 23 (36%) 94 (14%) 3.5 <.001 no ACS 41 (64%) 583 (86%)