Comorbidities in aging patients with sickle cell disease.

Sickle cell disease (SCD) in general and sickle cell anemia in particular is a highly complex disorder both at the molecular and clinical levels. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of the disease. Moreover, despite the fact that SCD is a chronic malady, its manifestations are both acute and chronic. The former include, among other things, the recurrent vaso-occlusive crises (its hallmark) and acute chest syndrome. The chronic complications include most commonly avascular necrosis and leg ulcers. Currently, survival of patients with SCD has improved dramatically thanks to newborn screening, antibiotic prophylaxis, better vaccine, safer blood transfusion and the use of hydroxyurea. It is the advent of these therapies that improved the survival. This improvement, however, introduced a third dimension of the disease: comorbidities that occur in aging people in the general population. There is concern that the gain in survival may be offset by the comorbidities. Thus it is the purpose of this review to identify the comorbidities in the elderly with SCD and differentiate them from the basis disease to implement proper therapies so that better survival could be maintained

Biomedical Research, A Tool to Address the Health Issues that Affect African Populations.

Traditionally, biomedical research endeavors in low to middle resources countries have focused on communicable diseases. However, data collected over the past 20 years by the World Health Organization (WHO) show a significant increase in the number of people suffering from non-communicable diseases (e.g. heart disease, diabetes, cancer and pulmonary diseases). Within the coming years, WHO predicts significant decreases in communicable diseases while non-communicable diseases are expected to double in low and middle income countries in sub-Saharan Africa. The predicted increase in the non-communicable diseases population could be economically burdensome for the basic healthcare infrastructure of countries that lack resources to address this emerging disease burden. Biomedical research could stimulate development of healthcare and biomedical infrastructure. If this development is sustainable, it provides an opportunity to alleviate the burden of both communicable and non-communicable diseases through diagnosis, prevention and treatment. In this paper, we discuss how research using biomedical technology, especially genomics, has produced data that enhances the understanding and treatment of both communicable and non-communicable diseases in sub-Saharan Africa. We further discuss how scientific development can provide opportunities to pursue research areas responsive to the African populations. We limit our discussion to biomedical research in the areas of genomics due to its substantial impact on the scientific community in recent years however, we also recognize that targeted investments in other scientific disciplines could also foster further development in African countries

Pulmonary Complications and Lung Function Abnormalities in Children with Sickle Cell Disease

The pulmonary complications of sickle cell disease (SCD) have a high morbidity and mortality. Fatal pulmonary complications occur in 20% of adults; those with sickle chronic lung disease (SCLD) and pulmonary hypertension have a significantly increased mortality. Treatment of SCLD is only supportive. Recurrent acute chest syndrome (ACS) episodes are the major risk factor for SCLD, and ACS is the leading cause of death. Adults with SCD tend to have restrictive lung function abnormalities, whereas, in children, obstructive abnormalities are more frequent. Lung function abnormalities are common even in young children and may reflect their chronic anaemia and increased pulmonary capillary blood volume, which increases airway obstruction and may be responsible for their increased wheezing. Whether more aggressive treatment of anaemia would improve lung function and long-term outcomes merits testing. Children with SCD experience a decline in lung function, which is most rapid in younger children in whom ACS episodes are most common highlighting the importance of identifying effective strategies to prevent and optimally treat ACS

AAPT Diagnostic Criteria for Chronic Sickle Cell Disease Pain

Pain in sickle cell disease (SCD) is associated with increased morbidity, mortality, and high health care costs. Although episodic acute pain is the hallmark of this disorder, there is an increasing awareness that chronic pain is part of the pain experience of many older adolescents and adults. A common set of criteria for classifying chronic pain associated with SCD would enhance SCD pain research efforts in epidemiology, pain mechanisms, and clinical trials of pain management interventions, and ultimately improve clinical assessment and management. As part of the collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks public-private partnership with the U.S. Food and Drug Administration and the American Pain Society, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy initiative developed the outline of an optimal diagnostic system for chronic pain conditions. Subsequently, a working group of experts in SCD pain was convened to generate core diagnostic criteria for chronic pain associated with SCD. The working group synthesized available literature to provide evidence for the dimensions of this disease-specific pain taxonomy. A single pain condition labeled chronic SCD pain was derived with 3 modifiers reflecting different clinical features. Future systematic research is needed to evaluate the feasibility, validity, and reliability of these criteria. Perspective: An evidence-based classification system for chronic SCD pain was constructed for the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy initiative. Applying this taxonomy may improve assessment and management of SCD pain and accelerate research on epidemiology, mechanisms, and treatments for chronic SCD pain

Sickle cell disease: Wheeze or asthma?

Sickle cell disease (SCD) is the most common life-limiting genetic disease among African Americans, affecting more than 100,000 people in the United States. Respiratory disorders in patients with sickle cell disease have been associated with increased morbidity and mortality. Associations between asthma and pain, acute chest syndrome (ACS), and even death have long been reported. More recently wheezing, even in the absence of an asthma diagnosis, has gained attention as a possible marker of SCD severity. Several challenges exist with regards to making the diagnosis of asthma in patients with SCD, including the high prevalence of wheezing, evidence of airway obstruction on pulmonary function testing, and/or airway hyperresponsiveness among patients with SCD. These features often occur in isolation, in the absence of other clinical criteria necessary for an asthma diagnosis. In this review we will summarize: 1) Our current understanding of the epidemiology of asthma, wheezing, airway obstruction, and airway responsiveness among patients with SCD; 2) The evidence supporting associations with SCD morbidity; 3) Our understanding of the pathophysiology of airway inflammation in SCD; 4) Current approaches to diagnosis and management of asthma in SCD; and 5) Future directions

Asthma in Sickle Cell Disease: Implications for Treatment

Objective. To review issues related to asthma in sickle cell disease and management strategies. Data Source. A systematic review of pertinent original research publications, reviews, and editorials was undertaken using MEDLlNE, the Cochrane Library databases, and CINAHL from 1947 to November 2010. Search terms were [asthma] and [sickle cell disease]. Additional publications considered relevant to the sickle cell disease population of patients were identified; search terms included [sickle cell disease] combined with [acetaminophen], [pain medications], [vitamin D], [beta agonists], [exhaled nitric oxide], and [corticosteroids]. Results. The reported prevalence of asthma in children with sickle cell disease varies from 2% to approximately 50%. Having asthma increases the risk for developing acute chest syndrome , death, or painful episodes compared to having sickle cell disease without asthma. Asthma and sickle cell may be linked by impaired nitric oxide regulation, excessive production of leukotrienes, insufficient levels of Vitamin D, and exposure to acetaminophen in early life. Treatment of sickle cell patients includes using commonly prescribed asthma medications; specific considerations are suggested to ensure safety in the sickle cell population. Conclusion. Prospective controlled trials of drug treatment for asthma in patients who have both sickle cell disease and asthma are urgently needed

Asthma, Airway Hyperresponsiveness, and Lower Airway Obstruction in Children with Sickle Cell Disease

As a comorbid condition of sickle cell disease (SCD), asthma leads to increased complications and mortality. However, poor understanding of asthma phenotypes in SCD and the complex interaction with SCD-related airway inflammation, manifested by bronchial hyperresponsiveness or obstructive airway, pose a unique clinical challenge. The objective of this chapter is to provide a comprehensive review and discussion of epidemiology, pathophysiology, interactions, and clinical implications of airway hyperresponsiveness (AHR), obstructive airway, and asthma in SCD. Discussion will cover new understanding and limitations of asthma diagnosis and management in SCD. AHR, lower obstructive airway, and asthma are highly prevalent in SCD. Despite overlapping features, these entities are nonetheless distinct as demonstrated by basic science and clinical data. Diagnosis of asthma should be based on a physician assessment. We provide new unpublished data of a prospective study on diagnosing asthma in a small preschool population. Administered validated asthma-screening questionnaire to SCD children reveals good sensitivity and specificity as an asthma detection tool. It is unclear at this time if detection of bronchial lability or asthma early in life would result in better outcome of patients, or if improved control of SCD attenuates lower airway pathology. Being able to distinguish asthma from bronchial lability in the preschool age children would allow for appropriate intervention early in life

National Heart, Lung, and Blood Institute (NHLBI) Strategy for Addressing Health Disparities

Throughout its history, the NHLBI has been a leader in conducting and supporting research to alleviate the health disparities that exist between various segments of the U.S. population, and its outstanding efforts in this area have been publicly recognized in Congressional hearings. Projects with a strong minority component have been initiated so that comparisons may be made between various populations. These projects have produced a wealth of information that enable identification of health disparities and provide clues about their causes