Randomised pilot trial of cash incentives for reducing paediatric asthmatic tobacco smoke exposures from maternal caregivers and members of their social network.

BACKGROUND: The primary aim was to evaluate the efficacy of financial incentives for reducing paediatric tobacco smoke exposures (TSEs) through motivating cigarette usage reduction among low-income maternal caregivers and members of their social network. DESIGN: Randomised control pilot trial over a 6-month study follow-up time period. The study was undertaken from May 2017 to -May 2018. Once monthly follow-up visits occurred over the 6-month study period. SETTING: Baltimore City, Maryland, USA. PARTICIPANTS: We grouped 135 participants into 45 triads (asthmatic child (2-12 years of age), maternal caregiver and social network member). Triads were assigned in a 1:1 allocation ratio. The maternal caregiver and social network members were active smokers and contributed to paediatric TSE. INTERVENTIONS: Triads were randomised to receive either usual care (TSE education and quitline referrals) or usual care plus financial incentives. Cash incentives up to $1000 were earned by caregivers and designated social network participants. Incentives for either caregivers or social network participants were provided contingent on their individual reduction of tobacco usage measured by biomarkers of tobacco usage. Study visits occurred once a month during the 6-month trial. MAIN OUTCOME MEASURES: The main outcome measure was mean change in monthly paediatric cotinine levels over 6 months of follow-up interval and was analysed on an intention-to-treat basis. RESULTS: The mean change in monthly child cotinine values was not significantly different in the intervention cohort over the 6-month follow-up period, compared with the control group (p=0.098, CI -0.16 to 1.89). Trends in child cotinine could not be ascribed to caregivers or social network members. Despite decreasing mean monthly cotinine values, neither the intervention cohort's caregivers (difference in slope (control-intervention)=3.30 ng/mL/month, CI -7.72 to 1.13, p=0.144) or paired social network members (difference in slope (control-intervention)=-1.59 ng/mL/month, CI -3.57 to 6.74, p=0.546) had significantly different cotinine levels than counterparts in the control group. CONCLUSIONS: Financial incentives directed at adult contributors to paediatric TSE did not decrease child cotinine levels. TRIAL REGISTRATION NUMBER: NCT03099811.

Linkage of Maternal Caregiver Smoking Behaviors on Environmental and Clinical Outcomes of Children with Asthma: A Post-Hoc Analysis of a Financial Incentive Trial Targeting Reduction in Pediatric Tobacco Smoke Exposures.

(1) Background: Monthly variability in smoking behaviors in caregivers of pediatric asthmatics yields questions of how much and when does smoking reduction result in improved environmental and clinical outcomes. (2) Methods: Post hoc analysis of data from a 6 month pilot randomized-control trial occurring from May 2017 to May 2018 in Baltimore City (MD, USA). The initial trial's primary intervention explored the utility of financial incentives in modifying caregiver smoking behaviors. Post hoc analyses examined all dyads independent of the initial trial's randomization status. All caregivers received pediatric tobacco smoke harm reduction education, in addition to monthly encouragement to access the state tobacco quitline for individual phone-based counseling and nicotine replacement therapy. Maternal caregivers who were active cigarette smokers and their linked asthmatic child (aged 2-12 years) were grouped into two classifications ("high" versus "low") based on the child and caregiver's cotinine levels. A "low" cotinine level was designated by at least a 25% reduction in cotinine levels during 3 months of the trial period; achieving ≤2 months of low cotinine levels defaulted to the "high" category. Twenty-seven dyads (caregivers and children) (total n = 54) were assigned to the "high" category, and eighteen dyads (caregivers and children) (total n = 36) were allocated to the "low" category. The primary outcome measure was the correlation of caregiver cotinine levels with pediatric cotinine values. Secondary outcomes included asthma control, in addition to caregiver anxiety and depression. (3) Results: Caregivers with 3 months of ≥25% decrease in cotinine levels had a significantly greater mean change in child cotinine levels (p = 0.018). "Low" caregiver cotinine levels did not significantly improve pediatric asthma control (OR 2.12 (95% CI: 0.62-7.25)). Caregiver anxiety and depression outcomes, measured by Patient Health Questionnaire (PHQ)-4 scores, was not significantly different based on cotinine categorization (p = 0.079); (4) Conclusion: Reduced pediatric cotinine levels were seen in caregivers who reduced their smoking for at least 3 months, but clinical outcome measures remained unchanged.

Alignment of Medical and Psychosocial Sectors for Promotion of Tobacco Cessation among Residents of Public Housing: A Feasibility Study.

The inequity in cessation resources is at the forefront of the recently enacted US smoking ban in public housing facilities. This pre-post, non-randomized pilot study assessed the feasibility of a smoking cessation program targeting smokers in Baltimore City public housing. The study implemented a four-phased, 10-week, community-based cessation program using a joint academic-housing partnership that provided on-site cessation pharmacotherapy, behavioral counseling, and psychosocial/legal services. The community-led strategy involved: (1) two-week smoking cessation training for lay health workers; (2) screening and recruitment of smokers by housing authority residential leadership; (3) four-week resident-led cessation using evidenced-based strategies along with wraparound support services; (4) formative evaluation of the intervention's acceptability and implementation. Thirty participants were recruited of which greater than one-half attended the majority of weekly cessation events. Thirty percent were able to achieve biomarker-proven cessation, as measured by a reduction in exhaled CO levels-a percentage comparable to the reported state quitline 30-day cessation rate. Despite weekly joint community-academic led-education of nicotine replacement therapy (NRT) therapies, only two participants regularly and properly used NRT transdermal patches; <20% of participants used NRT gum correctly at their first follow-up visit. Less than one-half utilized psychosocial and legal services by our community-based organization partners. Post-intervention interviews with participants noted broad approval of the ease in accessibility of the cessation intervention, but more diversification in the timing and personalization of offerings of services would have assisted in greater adoptability and participant retention. Though a reduction in smoking behaviors was not broadly observed, we elucidated modifiable social, educational, and physical features that could enhance the likelihood of smoking cessation among public housing residents.

The case for exploring the usage of employee wellness programs for pediatric asthma control.

The multiple socioecological determinants of asthma mandate that pediatricians develop a treatment strategy beyond the practice-based setting. To expand to a more impactful community-based role, pediatricians must look to form partnerships with groups that are capable of promoting social and environmental change. Traditionally, these groups have included schools, governmental agencies, and child care establishments. One group that is not actively being availed of are employers who have shown success in improving adult-based outcomes through wellness programs. Employers are stakeholders in pediatric asthma care through its impact on reduced worker productivity and higher health insurance premiums. An employer's focus on pediatric asthma will be a collective win for the employer and employee. The article herein describes the rationale for the focus of employers on pediatric asthma care and potential incorporation within employer-based wellness strategies.

Exploring the barriers and incentive architecture for modifying smoke exposures among asthmatics.

BACKGROUND: The socio-structural barriers for reducing secondhand smoke exposure (SHSe) among children with asthma may be insurmountable for low-income caregivers. Health promoting financial incentives (HPFIs) are increasingly being used in the adult population to motivate and sustain tobacco-reduction behaviors. We assessed barriers to SHSe reduction and means to overcome them through the design of an HPFI-based, caregiver-targeted SHSe reduction study. METHODS: Using a mixed-methods design, we conducted semi-structured in-depth interviews among low-income primary caregivers of children with asthma residing in Baltimore City. Quantitative data using an online survey were used to augment interview findings. RESULTS: Home smoking restrictions were a frequently referenced strategy for decreasing SHSe, but interviewees (n = 22) described the complex social pressures that undermine reduction efforts. Caregivers redirected conversations from broadly implemented smoking bans towards targeted reduction strategies among mothers and members of their social network who are active smokers. Participants converged on the notion that sustainable SHSe reduction strategies are realizable only for mothers who are active smokers, possess high self-efficacy and social structures that promote cessation. Survey data (n = 56) clarified the multiple contexts that underlie pediatric SHSe and preferred HPFI architecture that included fixed, recurrent payments contingent on reduced nicotine biomarkers and completion of basic asthma education classes. CONCLUSIONS: Based on the combined analyses, we envision testing a HPFI-based study design whose optimal target population included low-income caregivers and members of their social network where incentives are tied to pediatric biomarkers and asthma education-an integrated approach that has not yet been used in pediatric tobacco studies.

Cost Analysis of Motivational Interviewing and Preschool Education for Secondhand Smoke Exposures.

INTRODUCTION: This study determines if expenditures associated with implementing a combined motivational interviewing (MI) and Head Start-level education program (MI+Education), as compared to education alone, yield cost savings to society. METHODS: Post hoc cost analyses were applied to a randomized controlled-trial of MI among predominantly African American, low-income caregivers of 330 Baltimore City Head Start students who reside with a smoker. The primary outcome was the cost savings of MI+Education from averted direct secondhand smoke exposure (SHSe)-related acute healthcare events and inferred indirect costs (work days lost, transportation and reduction in cigarettes smoked). The net direction of savings was defined by the sum of averted direct and indirect costs of the MI+Education intervention at 3, 6 and 12 months, benchmarked against the Education alone cohort at the equivalent time periods. RESULTS: The costs saved by the MI+Education intervention, relative to Education alone, resulted in savings at solely the 12-month follow-up time point. Significant savings were appreciated from averted emergency department (ED) visits at 12 months ($4410; 95% simulation interval [SI]: $2241, $6626) for the MI+Education group. The total savings at 12 months ($2274; 95% SI: -3916, $8442) could not overcome additional program costs of implementing MI to Head Start-level education ($13 695; 95% SI: $11 250, $16 034). CONCLUSIONS: This study is the first to examine the cost of either intervention on SHSe-attributed pediatric healthcare costs from a population level relevant for federal and community decision makers. Intervention costs could not be offset by short-term savings but a trend towards positive savings was appreciated 1 year after implementation. IMPLICATIONS: Behavioral interventions are effective in reducing SHSe in children. However, many of these interventions are not implemented in community settings due to lack of resources and money. Behavioral strategies may be a cost-saving addition to the national initiatives to create smoke-free home environments. The long-term benefits of MI, as evidenced from cost savings from averted ED visits, appeared to show MI+Education to be a robust long-term strategy. The decrease of acute healthcare services at 12 months may be informative for policy decision makers seeking to allocate limited resources to reduce the usage of costly ED services and hospital readmissions.

Reducing Inpatient Length of Stay Using a Multicollaborative Protocol for Management of Non-Intensive Care Unit Asthmatics.

Maximizing clinical efficiency through the reduction in inpatient length of stay (LOS) using standardized protocols has been a major objective among hospital administrators, most notably in the context of recent healthcare reimbursement changes at statewide levels. The objective of our project was to determine whether a synchronous change in an inpatient asthma protocol that relied on a respiratory therapist (RT)-driven bronchodilator weaning algorithm and bronchodilator therapy given through a metered dose inhaler (MDI) plus valved holding chamber (VHC) could impact clinical and financial outcomes. A pre-post study assessed patients aged 2-21 years of age admitted with a primary diagnosis of status asthmaticus. The effect of the protocol was measured from October 2014 to July 2015. Outcome variables included patient demographics, hospital LOS, all-patient refined diagnosis-related groups (APR-DRGs), and inpatient charges. Outcomes were compared between the preimplementation and postimplementation time periods. Statistical significance was measured using Wilcoxon signed-rank test and bootstrap logistic regression models. Protocol patients (n = 110) had a similar demographic and clinical profile compared with the matched population from the previous nonprotocol fiscal year (n = 150). Use of the protocol resulted in a significantly reduced LOS that maintained significance after adjusting for APR-DRGs weight (P < 0.05). The protocol did not alter the total hospital billing charges. A nonstatistically significant reduction in 30-day readmission rates was observed among those administered the protocol. An RT-led weaning protocol using a quantitative scoring system and MDI+VHC for bronchodilator administration resulted in a significantly reduced LOS.

Special considerations--asthma in children.

BACKGROUND: Asthma is among the most common chronic diseases of childhood. Management of pediatric asthma requires an understanding of the issues that uniquely effect children. This review provides the reader with the current state and future directions of pediatric asthma. METHODS: Review of the pediatric asthma literature was undertaken with emphasis on randomized controlled trials and systematic reviews. RESULTS: The prevalence of pediatric asthma remains elevated and is increasingly being appreciated in select global regions. Effective treatment in any setting begins with a focused medical history that queries key asthma features that inform both diagnostic and monitoring strategies. A thorough medical history may yield comorbid upper airway disorders and allergic triggers that could potentially exacerbate airway inflammation. Pre-bronchodilator and post-bronchodilator lung function testing is a preferable diagnostic strategy to quantitatively assess obstructive pulmonary disease among children capable of performing the testing maneuvers. Pediatric asthmatics who continue to have poor disease control require monitoring of medication adherence and drug delivery techniques, because both are often linked with disease outcomes. Therapeutic strategies in children are notably distinct from adults due to the possible effects of inhaled corticosteroids on reduced bone mineral density and growth. Adolescents may also require more time to address the psychosocial complexities that may complicate the required daily usage of asthma medicines. CONCLUSION: Asthmatic children are distinct from their adult counterparts due to limitations inherent in the pediatric age group. A unified and evidence-based approach to pediatric asthma may improve clinical outcomes.

Pediatric asthma and ambient pollutant levels in industrializing nations.

Asthma is one of the most common chronic diseases in childhood and its prevalence has been increasing within industrializing nations. The contribution of ambient pollutants to asthma symptomatology has been explored in some countries through epidemiological investigations, molecular analysis and monitoring functional outcomes. The health effects of rising environmental pollution have been of increasing concern in industrializing nations with rising urbanization patterns. This review article provides an overview of the link between pediatric asthma and exposure to rising sources of urban air pollution. It primarily focuses on the asthma-specific effects of sulfur dioxide, nitrogen dioxide, ozone and particulate matter. Worldwide trends of asthma prevalence are also provided which detail the prominent rise in asthma symptoms in many urban areas of Africa, Latin America and Asia. The molecular and functional correlation of ambient pollutants with asthma-specific airway inflammation in the pediatric population are also highlighted. The final aspect of the review considers the correlation of motor vehicle, industrial and cooking energy sources, ascribed as the major emitters among the pollutants in urban settings, with asthma epidemiology in children.

Cost-consequence analysis of multimodal interventions with environmental components for pediatric asthma in the state of Maryland.

BACKGROUND: Applied environmental strategies for asthma control are often expensive, but may save longer-term healthcare costs. Whether these savings outweigh additional costs of implementing these strategies is uncertain. METHODS: We conducted a systematic review to estimate the expenditures and savings of environmental interventions for asthma in the state of Maryland. Direct costs included hospitalizations, emergency room, and clinic visits. Indirect expenditures included costs of lost work productivity and travel incurred during the usage of healthcare services. We used decision analysis, assuming a hypothetical cohort of the approximated 49,290 pediatric individuals in Maryland with persistent asthma, to compare costs and benefits of environmental asthma interventions against the standard of care (no intervention) from the societal perspective. RESULTS: Three interventions among nine articles met the inclusion criteria for the systematic review: 1) environmental education using medical professionals; 2) education using non-medical personnel; and 3) multi-component strategy involving education with non-medical personnel, allergen-impermeable covers, and pest management. All interventions were found to be cost-saving relative to the standard of care. Home environmental education using non-medical professionals yielded the highest net savings of $14.1 million (95% simulation interval (SI): $-.283 million, $19.4 million), while the multi-component intervention resulted in the lowest net savings of $8.1 million (95% SI: $-4.9 million, $15.9 million). All strategies were most sensitive to the baseline number of hospitalizations in those not receiving targeted interventions for asthma. CONCLUSIONS: Limited environmental reduction strategies for asthma are likely to be cost-saving to the healthcare system in Maryland and should be considered for broader scale-up in other economically similar settings.

Effect of residential proximity to major roadways on cystic fibrosis exacerbations.

Ambient air pollution has been attributed with an increase in exacerbation frequencies among the cystic fibrosis (CF) population. This study correlates exacerbation frequency with proximity to roadways and two criteria air pollutants. Clinical data was extracted from the Cystic Fibrosis Foundation National Patient Registry and Electronic Medical Records at Children's Hospital Los Angeles (CHLA). Average annual air pollutant levels were obtained from selected US Environmental Protection Agency's monitoring stations. Geographic proximity to monitoring stations and roadways were analyzed using spatial mapping software. A total of 145 patients from the CHLA's CF center were characterized by a dichotomous exacerbation category. No significant association was determined between the frequency of exacerbations and exposure to fine particulate matter and ozone levels. Residential proximity to US-designated highways and freeways also did not achieve significance (p = 0.3777) but was noted to be correlated with major arterial roadways (p = 0.0420). Associations of environmental exposures may have important implications for future predictive models of CF clinical outcomes.

2050: Ending the odyssey of the great white plague. Part of a series on Pediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni.

The United Nation's Millennium Development Goal of tuberculosis (TB) elimination by 2050 may be a realizable goal by concerting efforts of the numerous stakeholders involved in the development of novel antituberculous therapeutics. Improving pre-clinical models by the research community is one aspect of the drug development pipeline that will continue to require refinement. Better in vitro and animal models are needed to expand the chemical scaffolds of anti-TB agents. These constructs must be designed and utilized in a manner that is also pertinent to the pediatric population by addressing varying age-based drug metabolism rates. Novel technologies that utilize nanomedicine and genomic research may as well have a significant impact on future therapeutics; however, their development must acknowledge the key populations whose underlying disease pathology continues to drive the pandemic - both adults and children with latent TB, HIV/AIDS and diabetes. Challenging the long-standing orthodoxy of applying equivalent TB treatments for standard first line regimens among the adult and pediatric populations must also continue to be a major focus in future drug development strategies. Studies that include pediatric populations will require a greater variety of medication formulations, biomarkers that do not rely on sputum production and diagnostic technologies that are efficacious in paucibacillary disease. Significant programmatic barriers currently exist in key aspects of the described drug development pipeline, but strategic approaches can overcome these roadblocks - including the complex regulatory requirements involving the inclusion of children in drug trials. All such endeavors will require not only more focused research initiatives, but greater institutional support from the pharmaceutical industry, non-governmental organizations and national health sectors.

A modified scoring system to describe gross pathology in the rabbit model of tuberculosis.

BACKGROUND: The rabbit model is an ideal means to study the pathogenesis of tuberculosis due to its semblance to the disease in humans. We have previously described the results using a bronchoscopic route of infection with live bacilli as a reliable means of generating lung cavities in sensitized rabbits. The role of sensitization in the development of disease outcomes has been well established in several animal models. We have described here the varying gross pathology that result from lack of sensitization with heat-killed M. bovis prior to high-dose bronchoscopic infection with live bacilli. RESULTS: Rabbits lacking sensitization did not generate lung cavities, but instead formed solely a tuberculoid pneumonia that replaced the normal lung parenchyma in the area of infection. Extrapulmonary dissemination was seen in approximately equal frequency and distribution in both rabbit populations. Notable differences include the lack of intestinal lesions in non-sensitized rabbits likely due to the lack of ingestion of expectorated bacilli from cavitary lesions. The experiment also employed a modified scoring system developed initially in the primate model of tuberculosis to allow for the quantification of findings observed at necropsy. CONCLUSIONS: To date, no such scoring system has been employed in the rabbit model to describe gross pathology. The quantitative methodology would allow for rapid comparative analyses and standardization of thoracic and extrapulmonary pathology that could be evaluated for statistical significance. The aim is to use such a scoring system as the foundation for all future rabbit studies describing gross pathology at all stages in TB pathogenesis.

13[C]-urea breath test as a novel point-of-care biomarker for tuberculosis treatment and diagnosis.

BACKGROUND: Pathogen-specific metabolic pathways may be detected by breath tests based on introduction of stable isotopically-labeled substrates and detection of labeled products in exhaled breath using portable infrared spectrometers. METHODOLOGY/PRINCIPAL FINDINGS: We tested whether mycobacterial urease activity could be utilized in such a breath test format as the basis of a novel biomarker and diagnostic for pulmonary TB. Sensitized New-Zealand White Rabbits underwent bronchoscopic infection with either Mycobacterium bovis or Mycobacterium tuberculosis. Rabbits were treated with 25 mg/kg of isoniazid (INH) approximately 2 months after infection when significant cavitary lung pathology was present. [(13)C] urea was instilled directly into the lungs of intubated rabbits at selected time points, exhaled air samples analyzed, and the kinetics of delta(13)CO(2) formation were determined. Samples obtained prior to inoculation served as control samples for background (13)CO(2) conversion in the rabbit model. (13)CO(2), from metabolic conversion of [(13)C]-urea by mycobacterial urease activity, was readily detectable in the exhaled breath of infected rabbits within 15 minutes of administration. Analyses showed a rapid increase in the rate of (13)CO(2) formation both early in disease and prior to treatment with INH. Following INH treatment, all evaluable rabbits showed a decrease in the rate of (13)CO(2) formation. CONCLUSIONS/SIGNIFICANCE: Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and for treatment response. Future work will test specificity for M. tuberculosis using lung-targeted dry powder inhalation formulations, combined with co-administering oral urease inhibitors together with a saturating oral dose of unlabeled urea, which would prevent the delta(13)CO(2) signal from urease-positive gastrointestinal organisms.

Epidemiology and challenges to the elimination of global tuberculosis.

Recent epidemiological indicators of tuberculosis (TB) indicate that the Millennium Development Goal of TB elimination by 2050 will not be achieved. The majority of incident cases are occurring in population-dense regions of Africa and Asia where TB is endemic. The persistence of TB in the setting of poor existing health infrastructure has led to an increase in drug-resistant cases, exacerbated by the strong association with human immunodeficiency virus coinfection. Spreading drug resistance threatens to undo decades of progress in controlling the disease. Several significant gaps can be identified in various aspects of national- and international-directed TB-control efforts. Various governing bodies and international organizations need to address the immediate challenges. This article highlights some of the major policies that lawmakers and funding institutions should consider. Existing economic and social obstacles must be overcome if TB elimination is to be a reachable goal.

Extrapulmonary dissemination of Mycobacterium bovis but not Mycobacterium tuberculosis in a bronchoscopic rabbit model of cavitary tuberculosis.

The rabbit model of tuberculosis is attractive because of its pathophysiologic resemblance to the disease in humans. Rabbits are naturally resistant to infection but may manifest cavitary lung lesions. We describe here a novel approach that utilizes presensitization and bronchoscopic inoculation to reliably produce cavities in the rabbit model. With a fixed inoculum of bacilli, we were able to reproducibly generate cavities by using Mycobacterium bovis Ravenel, M. bovis AF2122, M. bovis BCG, M. tuberculosis H37Rv, M. tuberculosis CDC1551, and the M. tuberculosis CDC1551 DeltasigC mutant. M. bovis infections generated cavitary CFU counts of 10(6) to 10(9) bacilli, while non-M. bovis species and BCG yielded CFU counts that ranged from 10(4) to 10(8) bacilli. Extrapulmonary dissemination was almost exclusively noted among rabbits infected with M. bovis Ravenel and AF2122. Though all of the species yielded secondary lesions at intrapulmonary sites, M. bovis infections led to the most apparent gross pathology. Using the M. tuberculosis icl and dosR gene expression patterns as molecular sentinels, we demonstrated that both the cavity wall and cavity lumen are microenvironments associated with hypoxia, upregulation of the bacterial dormancy program, and the use of host lipids for bacterial catabolism. This unique cavitary model provides a reliable animal model to study cavity pathogenesis and extrapulmonary dissemination.

Spontaneous resolution of diffuse persistent pulmonary interstitial emphysema.

Persistent pulmonary interstitial emphysema (PPIE) is a rare condition that occurs in both preterm and term infants. It is thought to arise from a disruption of the basement membrane of the alveolar wall allowing air entry into the interstitial space. The characteristic CT scan appearance of PPIE can be used to differentiate it from other congenital cystic lesions that may present similarly. Although conservative management is accepted as the initial form of management in most cases, a review of the published literature found that a significant proportion of localized PPIE cases eventually require surgical resection. This case illustrates that extensive bilateral PPIE associated with a persistent pneumomediastinum can resolve spontaneously thus demonstrating that conservative management without surgical intervention may be appropriate for some children.