Identifying Clinical and Research Priorities in Sickle Cell Lung Disease. An Official American Thoracic Society Workshop Report.

Background: Pulmonary complications of sickle cell disease (SCD) are diverse and encompass acute and chronic disease. The understanding of the natural history of pulmonary complications of SCD is limited, no specific therapies exist, and these complications are a primary cause of morbidity and mortality.Methods: We gathered a multidisciplinary group of pediatric and adult hematologists, pulmonologists, and emergency medicine physicians with expertise in SCD-related lung disease along with an SCD patient advocate for an American Thoracic Society-sponsored workshop to review the literature and identify key unanswered clinical and research questions. Participants were divided into four subcommittees on the basis of expertise: 1) acute chest syndrome, 2) lower airways disease and pulmonary function, 3) sleep-disordered breathing and hypoxia, and 4) pulmonary vascular complications of SCD. Before the workshop, a comprehensive literature review of each subtopic was conducted. Clinically important questions were developed after literature review and were finalized by group discussion and consensus.Results: Current knowledge is based on small, predominantly observational studies, few multicenter longitudinal studies, and even fewer high-quality interventional trials specifically targeting the pulmonary complications of SCD. Each subcommittee identified the three or four most important unanswered questions in their topic area for researchers to direct the next steps of clinical investigation.Conclusions: Important and clinically relevant questions regarding sickle cell lung disease remain unanswered. High-quality, multicenter, longitudinal studies and randomized clinical trials designed and implemented by teams of multidisciplinary clinician-investigators are needed to improve the care of individuals with SCD.

Safety of tiotropium Respimat® in black or African-American patients with symptomatic asthma.

BACKGROUND: Black patients with asthma have a higher disease burden and greater morbidity compared with other racial/ethnic groups. Tiotropium Respimat®, as add-on to at least inhaled corticosteroids (ICS), improves lung function and asthma control and reduces asthma exacerbation risk in patients, with a safety profile comparable with placebo. This study aimed to assess the safety of tiotropium Respimat®, compared with placebo, in black or African-American patients. METHODS: Data were pooled from 12 randomized, placebo-controlled, parallel-group, Phase II or III trials from the global Boehringer Ingelheim program with once-daily tiotropium Respimat® (5 µg or 2.5 µg). Trial participants had symptomatic persistent asthma with a broad range of severities and were aged 1-75 years. The safety results of black or African-American patients were compared with the overall trial population. RESULTS: Of the 5165 patients treated with tiotropium or placebo, 3.2% were black or African American. For both doses of tiotropium, the proportion of patients reporting adverse events (AEs) was approximately 10% lower compared with placebo and was generally comparable with the proportion of patients reporting AEs in all groups of the overall population. The number of investigator-assessed drug-related AEs, AEs leading to trial drug discontinuation or serious AEs reported by patients was low and comparable between treatment groups and with the overall population. CONCLUSION: Tiotropium Respimat® appears to be a generally safe add-on bronchodilator treatment option to ICS with or without other controllers in pediatric and adult black or African-American patients with asthma. CLINICAL TRIAL IDENTIFIERS: NCT01634113, NCT01634139, NCT01634152, NCT01257230, NCT01277523, NCT01316380, NCT00350207, NCT01172808, NCT01172821, NCT01340209, NCT00772538, NCT00776984.

The impact of asthma exacerbations and preventive strategies.

OBJECTIVE: To review the pathophysiologic mechanisms underlying asthma exacerbations, the impact of exacerbations, and both current and future treatment strategies to establish asthma control and reduce the risk of future exacerbations. RESEARCH DESIGN AND METHODS: Relevant adult data were identified via PubMed, with additional references obtained by reviewing bibliographies from selected articles. RESULTS: Asthma exacerbations or 'attacks' are acute episodes of progressive worsening of symptoms which occur in patients with all degrees of asthma severity and are an important cause of morbidity and mortality. For patients, these asthma attacks constitute a considerable part of the disease burden in terms of both personal suffering and economic impact. Exacerbations are characterized in part by decreases in expiratory flow or lung function. The pathophysiologic mechanism underlying these changes is likely to be different depending on the specific asthma phenotype. Asthma exacerbations are commonly initiated by upper respiratory tract infections and/or environmental allergens, although there are other known factors which increase the risk of a patient developing exacerbations, such as cigarette smoking. Establishing asthma control and reducing the risk of future exacerbations is the main goal of asthma treatment. Inhaled corticosteroids alone or in combination with long-acting ß2-agonists, in addition to other step-up strategies such as leukotriene receptor antagonists and theophylline, are recommended. The anti-immunoglobulin E monoclonal antibody omalizumab should also be considered in difficult-to-treat allergic asthma. CONCLUSIONS: Despite the currently available treatments, many patients with asthma remain symptomatic and experience exacerbations regardless of disease severity. New therapies, including long-acting anticholinergics, anti-cytokines, and chemoattractant receptor-homologous molecules, are under investigation with some promising results. In addition to increased education and use of self-management plans, these novel therapies are essential to help improve asthma control and reduce exacerbation risk.

Racial disparities in pediatric asthma: a review of the literature.

The burden of asthma disproportionately affects children living in economically disadvantaged urban communities. The relationships between ethnicity, genetic differences, lower socioeconomic status, poor medication adherence, greater exposure to environmental triggers, and absence of regular asthma care all contribute to this disparity. This review aims to identify and discuss recent studies on additional factors that may also impact to pediatric asthma disparity. The body of work examined in this review suggests that these disparities are the result of gene-environment interactions, vitamin D metabolism, socioeconomic status, urban environment, healthcare setting, and associated health beliefs.

A new focus on assessing and treating asthma control in the African-American community: a call to action.

Asthma continues to be a highly prevalent disease characterized by significant morbidity, unnecessary mortality, and substantial cost to the health care system. After decades of increasing prevalence, the number of current asthmatics in recent years has plateaued at approximately 22 million people in the United States. An additional 10 million Americans have a past history of asthma that is not active. The burden of asthma is higher among African Americans than in any other racial or ethnic group in America. The African-American community continues to experience a disproportional increase in asthma prevalence, morbidity, and mortality. The educational initiatives stemming from the newly revised National Heart Lung and Blood Institute (NHLBI) guidelines provide the opportunity to address the increased burden of asthma in the African American community. These new guidelines, released in August 2007, focus on asthma control as the primary goal of therapy, routine monitoring of asthma control, and use of asthma control assessments to direct treatment. The present review discusses the following: I. The impact of health disparities on outcomes of African Americans with asthma, II. The barriers that prevent asthmatic patients from achieving optimal control, III. The unique factors that challenge practitioners and patients in achieving optimal asthma control in the African American Community, IV. The impact of good asthma control and the need for patients and clinicians to assess asthma control in with a standardized assessment tool, and V. Strategic initiatives and the role of the End The Attacks NOW program in improving outcomes for African American patients with asthma.

Classifying asthma.

The most widely known method of asthma classification is the severity classification recommended in the National Asthma Education and Prevention Program 1997 guidelines, which also formed the basis of the Global Initiative for Asthma guidelines. This method was developed to direct a hierarchy of asthma therapy based on the patient's severity of disease. However, this severity classification has not been validated and has a number of limitations; in particular, it is challenging for physicians to apply reliably. Moreover, it does not allow asthma control to be assessed after the initiation of treatment, even though symptom control is a key objective of the treatment guidelines. A number of tools have been evaluated to provide longitudinal information on asthma control, and some of these have been validated. Clinically relevant measures of inflammation, such as eosinophilic airway inflammation, may also be helpful in classifying asthma and in guiding the use of antiinflammatory therapy. This may be a particularly useful approach in patients who are asymptomatic but have poor lung function, by permitting physicians to determine whether inflammatory processes are active, thus requiring ICS therapy. In the clinical setting, easy-to-use tools are needed to enable longitudinal assessments of symptom control and (ideally) disease progression.

Preschool wheeze prognosis: how do we predict outcome?

Preschool wheezing is extremely common. Despite its prevalence, prognosis is often hard to determine. Preschool wheezing is not without significant associated morbidity which may result in increased utilization of medical resources. The child with preschool wheezing may represent one of at least three distinct phenotypes, each having different clinical significance and therapeutic implications. The challenge to the clinician is to correctly identify the operative phenotype as a basis for family education, effective therapy and ultimately a reasonable assertion regarding prognosis. The current article reviews clinical presentation, potential etiologies and triggers as well as historical, hereditary and laboratory markers that may aid in the diagnosis and management of this challenging presentation among preschool children.

All I need is the air that I breath: outdoor air quality and asthma.

In recent years, developing insight into the pathophysiology of asthma and advances in asthma management have been substantial. Despite these advancements, asthma remains a significant health problem in the paediatric population. In the USA, the prevalence of asthma in children under 18 years of age is estimated at 7% [US Environmental Health Protection Agency. Publication # EPA-100-r-018. Washington, DC, 2000]. Prevalence rates in various subpopulations, particularly African and Hispanic Americans, are much higher. Certain inner-city census tracts have estimated prevalence rates of 20 to 25% [ Crain EF Weiss KP, Stein REK. Pediatric 1994; 94: 356-362]. Many of these subpopulations experience alarmingly disparate and apparently increasing morbidity and mortality associated with asthma. Similar trends in prevalence and morbidity have been observed in urban populations outside the USA as well [Sears MR. Lancet 1997; 350: 1015-1020]. There is considerable controversy as to the scientific basis for these observed trends. While the identification of a single factor or even a closely related group of factors appears unlikely, there is considerable speculation about the role of environmental factors, particularly outdoor air quality. In the USA, the National Ambient Air Quality Standards (NAAQs) offer specific standards for air quality. These standards are applied to certain criteria pollutants, including ozone, particulate matter (both PM(10) and PM(2.5)), sulfur dioxide, nitrogen dioxide, lead and carbon monoxide [ Committee on Environmental Health, AAP. In: Handbook of Pediatric Environmental Health. Elk Grove Village, IL, 1999; 181-191]. The NAAQs were recently revised for both ozone and particulate matter based on data that suggested health risks existed at levels below those set forth in the previous standards. Monitoring data reveals that urban populations are more likely to be exposed to elevated levels of these pollutants [Dickey JH. Disease Monitor 2000; 46(9): 566-589]. Children are uniquely predisposed to the potential harmful effects of these pollutants. This predisposition is related to unique physiologic, anatomic and behavioural characteristics of the infant, child and adolescent. There is compelling evidence that an interplay of genetic predisposition and environmental exposure to a number of chemical and infectious agents may be operative in both the inception and persistence of the clinical asthma phenotype. The relative role of the criteria air pollutants in this interplay is the subject of considerable study. The potential value of intervention by regulatory agencies or by behavioural modification among individuals or communities should be explored. At the very least, the current data offers implications for situational strategies of asthma management based on local monitoring data.

Balancing safety and efficacy in the treatment of pediatric asthma.

The treatment of pediatric asthma requires balancing the efficacy and safety of various asthma medications, facilitating patient and family education, and developing a supportive treatment network. The efficacy and safety of the major asthma controllers--cromolyn, long-acting beta(2)-agonists, inhaled corticosteroids, and leukotriene receptor antagonists-are well tolerated overall when used appropriately. Cromolyn is used often as first-line therapy in treating pediatric asthma, but the inhaled corticosteroids remain the cornerstone of pediatric asthma control. Long-acting beta(2)-agonists are most beneficial when used intermittently or in combination with other asthma medications. The most recent class of drugs, the leukotriene receptor antagonists are effective in controlling asthma and are well tolerated in children as young as 2 years of age. In moderate-to-severe pediatric asthma, combination therapy is often required to achieve optimal asthma control. Leukotriene receptor antagonists combined with inhaled corticosteroids reduce the need for steroid rescue, the rate of serious exacerbations, and the level of inflammation. The treatment of asthma requires the ability to diagnose and treat asthma effectively. In subpopulations with special needs such as very young or inner-city minority children, treating asthma requires a comprehensive approach that includes a supportive patient-physician relationship and the involvement of schools, churches, and neighborhood outreach programs that will identify children with asthma and promote quality care.