A comparison of tiotropium, long-acting ß2-agonists and leukotriene receptor antagonists on lung function and exacerbations in paediatric patients with asthma.

Diagnosing and treating asthma in paediatric patients remains challenging, with many children and adolescents remaining uncontrolled despite treatment. Selecting the most appropriate pharmacological treatment to add onto inhaled corticosteroids (ICS) in children and adolescents with asthma who remain symptomatic despite ICS can be difficult. This literature review compares the efficacy and safety of long-acting ß2-agonists (LABAs), leukotriene receptor antagonists (LTRAs) and long-acting muscarinic antagonists (LAMAs) as add-on treatment to ICS in children and adolescents aged 4-17 years.A literature search identified a total of 29 studies that met the inclusion criteria, including 21 randomised controlled trials (RCTs) of LABAs versus placebo, two RCTs of LAMAs (tiotropium) versus placebo, and four RCTs of LTRA (montelukast), all as add-on to ICS. In these studies, tiotropium and LABAs provided greater improvements in lung function than LTRAs, when compared with placebo as add-on to ICS. Although exacerbation data were difficult to interpret, tiotropium reduced the risk of exacerbations requiring oral corticosteroids when added to ICS, with or without additional controllers. LABAs and LTRAs had a comparable risk of asthma exacerbations with placebo when added to ICS. When adverse events (AEs) or serious AEs were analysed, LABAs, montelukast and tiotropium had a comparable safety profile with placebo.In conclusion, this literature review provides an up-to-date overview of the efficacy and safety of LABAs, LTRAs and LAMAs as add-on to ICS in children and adolescents with asthma. Overall, tiotropium and LABAs have similar efficacy, and provide greater improvements in lung function than montelukast as add-on to ICS. All three controller options have comparable safety profiles.

"Black People Like Me": A virtual conference series to engage underserved patients with asthma in patient centered outcomes research.

BACKGROUND: In response to racial inequity in asthma, asthma-related research among diverse patients is vital. However, people from historically marginalized groups are underrepresented in clinical and patient-centered outcomes research (PCOR). The "Black People Like Me" (BPLM) virtual conference series was developed to: (1) engage Black patients with asthma and their caregivers in education and discussions about asthma, and (2) encourage involvement in PCOR. Education about COVID-19 and COVID-19 vaccination was also incorporated. METHODS: The Project Advisory Group consisting of Black patients, clergy, physicians, and a program evaluator met monthly to develop BPLM. The program consisted of free one-hour virtual sessions held monthly for 6 months. BPLM was promoted through the Allergy & Asthma Network website, emails, social media, and personal contacts with a recruitment goal of ≥ 100 Black patients with asthma or caregivers. Program evaluations, interactive polling questions during each session, and participant pre- and post-session tests were conducted. RESULTS: Sessions averaged 658 participants including Black patients, family members, caregivers, Black clergy, health care providers, and other concerned community. Overall, 77% of participants strongly agreed with satisfaction with the sessions. Pre- and post-tests demonstrated that participants exhibited growth in knowledge regarding asthma risk, PCOR, and PCOR research opportunities for patients, exhibited preexisting and sustained knowledge regarding COVID-19 vaccination and side effects, and demonstrated an increased sense of empowerment during healthcare visits. CONCLUSIONS: BPLM demonstrated that a virtual platform can successfully engage Black communities. Incorporating clergy and religious organizations was critical in developing the trust of the Black community towards BPLM.

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.

Characteristics Relevant To Respiratory Health Among African Americans Attending Church-based Asthma Programs in Atlanta.

BACKGROUND: Not One More Life (NOML), a health and faith partnership, aims to engage African Americans at risk for asthma morbidity into community-partnered asthma programs. METHODS: Not One More Life programs consisted of interactive presentations, a questionnaire, and spirometry. RESULTS: 4,522 individuals attended NOML programs at 136 Atlanta churches over nine years. Over 90% of attendees were African American. Attendees with asthma had high rates of obesity (9.4% of children, 47.9% of adults) and airflow obstruction (34.6% of children, 17.2%, of adults). Over 20% of attendees with asthma reported past hospitalization for asthma. Among those with a history of hospitalizations for asthma, just 17.6% reported treatment with inhaled corticosteroids Conclusion. Not One More Life program attendees with asthma report considerable morbidity including exceptionally high rates of asthma hospitalizations. Participants have multiple remediable characteristics associated with poorly controlled asthma, including medication undertreatment and obesity.

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.

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.

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.

Safety and efficacy of tiotropium in children aged 1-5 years with persistent asthmatic symptoms: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Few studies have assessed the safety and efficacy of potential asthma medications in children younger than 5 years. We descriptively assessed the safety and efficacy of tiotropium, a long-acting anticholinergic drug, in children aged 1-5 years with persistent asthmatic symptoms. METHODS: This exploratory 12-week, randomised, double-blind, placebo-controlled, parallel-group, phase 2/3, regulatory multicentre trial was done at 32 hospitals, clinics, and clinical research units in 11 countries in Asia, Europe, and North America. Children aged 1-5 years with at least a 6-month history of persistent asthmatic symptoms and a need for inhaled corticosteroids were eligible. Patients were randomly allocated using an interactive voice or web-based response system to receive once-daily tiotropium 2·5 µg, tiotropium 5 µg, or placebo as an add-on to inhaled corticosteroids with or without additional controller medication. Patients and investigators were masked to study group assignment. Tiotropium was given via the Respimat inhaler once daily as two puffs of 1·25 µg in the 2·5 µg group, two puffs of 2·5 µg in the 5 µg group, or two puffs of placebo. The primary outcomes were safety, which was assessed by comparing adverse events between the tiotropium and placebo groups, and efficacy, which was measured as the change in weekly mean combined daytime asthma symptom score from baseline to week 12. Statistical analyses of treatment effects were exploratory; although endpoints were defined, they were used for descriptive analyses only. The safety and primary analyses were done in all patients who received at least one dose of their assigned treatment. This study is registered with ClinicalTrials.gov (NCT01634113), and is completed. FINDINGS: Between July 26, 2012, and Dec 4, 2014, 102 children were randomly assigned to the three treatment groups (36 to receive tiotropium 2·5 µg, 32 to receive tiotropium 5 µg, and 34 to receive placebo). 101 children completed the study and were included in the analyses. The changes in adjusted weekly mean combined daytime asthma symptom scores between baseline and week 12 were not significantly different between any of the groups. The adjusted mean difference between the tiotropium 2·5 µg group and placebo group was -0·080 (95% CI -0·312 to 0·152) and the difference between tiotropium 5 µg and placebo group was -0·048 (-0·292 to 0·195). Adverse events were less frequent with tiotropium treatment than with placebo (20 [56%] of 36 children with tiotropium 2·5 µg, 18 [58%] of 31 with tiotropium 5 µg, and 25 [74%] of 34 with placebo), although no formal statistical comparison between groups was performed. A greater proportion of children reported asthma exacerbations as adverse events in the placebo group (ten [29%] of 34) than in the tiotropium groups (five [14%] of 36 in the 2·5 µg group and two [6%] of 31 in the 5 µg group). Serious adverse events were reported in three patients (all of whom received placebo); no adverse events led to discontinuation of treatment or death. INTERPRETATION: To our knowledge, our small study is the first to assess the safety and efficacy of tiotropium in children aged 1-5 years with persistent asthmatic symptoms. Tolerability of tiotropium was similar to that of placebo, which is consistent with previous findings in older populations. Although mean daytime asthma symptom scores were not significantly different between groups, tiotropium showed the potential to reduce asthma exacerbation risk compared with placebo. The findings of the study are limited by the small sample size and descriptive statistical analyses. Additional well powered trials are needed to further assess the safety and efficacy of tiotropium in young children. FUNDING: Boehringer Ingelheim.

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.

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.

Community health screenings can complement public health outreach to minority immigrant communities.

OBJECTIVES: We sought to provide culturally competent, community-based respiratory health screening and education in minority communities with high concentrations of Latino immigrants on Long Island and to assess the impact of this intervention on their decision to seek medical care. METHODS: Seven health care screenings were performed in communities with high concentrations of immigrants from Latin America. A subgroup of participants who identified themselves as Hispanic/Latino were analyzed. After completion of a respiratory health questionnaire and spirometry, screening scores were calculated, education provided, and recommendations were made for medical evaluation in those who screened positive. A positive screen was defined as abnormal respiratory symptoms, abnormal spirometry, or both. Follow-up contacts were made at 1, 6, and 12 months to assess compliance with the recommendation to seek care in those who screened positive. RESULTS: High positive screening rates for both men (64%) and women (61%) were found. Of the participants who screened positive and were advised to seek medical care, 52% did so. Compliance with the recommendation to seek care was associated with the presence of an identified medical provider at baseline. Of those who screened positive and who did not comply with team's recommendation, 75% were unable to identify a health care provider. CONCLUSIONS: A significant number of participants who screened positive could not identify a health care provider and did not follow-up with the recommendation to seek medical evaluation. Community-based screenings provide an opportunity to access at-risk immigrant populations for health screening and education, and to facilitate referral and access to medical services.

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.