In this review, we examine the known and suspected toxicity of electronic cigarettes (e-cigarettes) in adolescents and young adults, to improve awareness of risks and identification of complications ...of their use. The use of e-cigarettes, or "vaping," is exploding among the pediatric population. E-cigarettes heat a solution containing a psychoactive compound, most commonly nicotine or tetrahydrocannabinol (THC), along with flavorings and other additives to a vapor, which users inhale. Since their introduction in the early 2000s, e-cigarette use is now prolific among youth, per the Monitoring the Future survey, with over 40% of high school seniors reporting use within the past year. Adolescents are vulnerable to the risks of e-cigarettes, as they are targeted as new consumers with advertisements and flavoring compounds, and are not utilizing them as a means to smoking cessation. The pulmonary risks of vaping are rapidly emerging, with the most immediately alarming being the condition electronic-cigarette/vaping associated lung injury (EVALI). Additionally, there have been more recent studies showing extrapulmonary effects including cardiovascular, immunologic and neuro-developmental effects. Many of these effects are likely dose-dependent. Public health efforts are urgently needed to decrease or eliminate new e-cigarette initiation, and support should be established to assist current e-cigarette users with cessation. We strongly advocate for the elimination of e-cigarette flavorings and advertising directed at adolescents, and call for physicians to be cognizant of this expanding epidemic.
Alongside the epidemic use of electronic cigarettes (e‐cigarettes) across the country, evidence of multiple pulmonary complications has emerged, with the most immediately life‐threatening being the ...new clinical condition of e‐cigarette/vaping‐associated lung injury (EVALI), with investigation actively underway to further define this entity and determine the cause or causes. We present a series of cases of respiratory illnesses associated with e‐cigarette use, many of which meet criteria for suspected or confirmed EVALI, managed at a pediatric tertiary care center, demonstrating notable variation in presenting symptoms and severity. Most cases improved with supportive respiratory care and the administration of corticosteroids and antibiotics, although generally no infection was found. The cases also tend to show improvement with discontinuation of the use of e‐cigarettes. We discuss challenges in determining the contribution of e‐cigarettes to the case pathology and review possible diagnostic and treatment options. In patients suffering from e‐cigarette‐related respiratory illness including EVALI, the primary treatment goal should be the cessation of e‐cigarette use and avoidance of other possible pulmonary toxins, including conventional cigarettes. Prevention of e‐cigarette use is critical in the youth population, as these patients are typically nicotine naïve and do not engage in smoking conventional cigarettes before initiation of vaping.
Electronic (e)-cigarette use and the practice of vaping has rapidly expanded both in adult smokers and previously nicotine naïve youths. Research has focused on harm reduction in adults using ...e-cigarettes to stop or reduce traditional cigarette use, but the short and long-term safety of these products has not been established. Vaping has more recently been associated with a growing list of pulmonary complications with the most urgent being the e-cigarette or vaping product use-associated lung injury (EVALI) epidemic. This review details the inhalant toxicology of vaping products, the described lung diseases associated with vaping with a focus on EVALI, and the predicted long-term consequences of e-cigarette use, including increased asthma severity.
Recessive mutations in the ATP-binding cassette transporter A3 (ABCA3) cause lethal neonatal respiratory failure and childhood interstitial lung disease. Most ABCA3 mutations are private.
To ...determine genotype-phenotype correlations for recessive ABCA3 mutations.
We reviewed all published and unpublished ABCA3 sequence and phenotype data from our prospective genetic studies of symptomatic infants and children at Washington and Johns Hopkins Universities. Mutations were classified based on their predicted disruption of protein function: frameshift and nonsense mutations were classified as "null," whereas missense, predicted splice site mutations, and insertion/deletions were classified as "other." We compared age of presentation and outcomes for the three genotypes: null/null, null/other, and other/other.
We identified 185 infants and children with homozygous or compound heterozygous ABCA3 mutations and lung disease. All of the null/null infants presented with respiratory failure at birth compared with 75% of infants with null/other or other/other genotypes (P = 0.00011). By 1 year of age, all of the null/null infants had died or undergone lung transplantation compared with 62% of the null/other and other/other children (P < 0.0001).
Genotype-phenotype correlations exist for homozygous or compound heterozygous mutations in ABCA3. Frameshift or nonsense ABCA3 mutations are predictive of neonatal presentation and poor outcome, whereas missense, splice site, and insertion/deletions are less reliably associated with age of presentation and prognosis. Counseling and clinical decision making should acknowledge these correlations.
Over the past decade, researchers have shifted their focus from documenting health care disparities to identifying solutions to close the gap in care. Finding Answers: Disparities Research for ...Change, a national program of the Robert Wood Johnson Foundation, is charged with identifying promising interventions to reduce disparities. Based on our work conducting systematic reviews of the literature, evaluating promising practices, and providing technical assistance to health care organizations, we present a roadmap for reducing racial and ethnic disparities in care. The roadmap outlines a dynamic process in which individual interventions are just one part. It highlights that organizations and providers need to take responsibility for reducing disparities, establish a general infrastructure and culture to improve quality, and integrate targeted disparities interventions into quality improvement efforts. Additionally, we summarize the major lessons learned through the Finding Answers program. We share best practices for implementing disparities interventions and synthesize cross-cutting themes from 12 systematic reviews of the literature. Our research shows that promising interventions frequently are culturally tailored to meet patients’ needs, employ multidisciplinary teams of care providers, and target multiple leverage points along a patient’s pathway of care. Health education that uses interactive techniques to deliver skills training appears to be more effective than traditional didactic approaches. Furthermore, patient navigation and engaging family and community members in the health care process may improve outcomes for minority patients. We anticipate that the roadmap and best practices will be useful for organizations, policymakers, and researchers striving to provide high-quality equitable care.
Rationale
As a result of the SARS‐CoV‐2 pandemic, all pediatric pulmonary fellowship programs conducted virtual interviews for the first time in the Fall of 2020. This study aimed to understand the ...accuracy of virtual‐interview derived‐impressions of fellowship programs, as well as applicant preference for future fellowship interview cycles.
Methods
A group of pediatric pulmonary fellows and Program Directors designed a REDCap survey. The survey was distributed to all first‐year pediatric pulmonary fellows who participated in the 2020–2021 virtual interview season.
Results
23/52 (44%) of first‐year pediatric pulmonary fellows completed the survey. 96% were able to form general impressions about fellowship programs during their virtual interviews. 96% reported that generally their fellowship experience matched their virtual‐interview derived‐impressions. 17 of the 19 factors applicants use to rank programs had no statistically significant change (p > 0.05) in impression from virtual interview to fellowship experience. The two factors with a statistically significant (p < 0.05) change in impression were patient care related—volume of “bread and butter” pediatric pulmonary patients and volume of tertiary care pediatric pulmonary patients. 87% prefer some form of in‐person interview option in future application cycles. A tiered interview format in which applicants are first invited to a virtual interview day followed by an optional in‐person second look day was the most popular preference for future interview cycles (48%).
Conclusions
Virtual interviews may provide accurate representations of pediatric pulmonary fellowship programs and applicants prefer some type of in‐person interview option in future application cycles.
Niemann-Pick Disease Type C (NPC) is an inherited, often fatal neurovisceral lysosomal storage disease characterized by cholesterol accumulation in every cell with few known treatments. Defects in ...cholesterol transport cause sequestration of unesterified cholesterol within the endolysosomal system. The discovery that systemic administration of hydroxypropyl-beta cyclodextrin (HPβPD) to NPC mice could release trapped cholesterol from lysosomes, normalize cholesterol levels in the liver, and prolong life, led to expanded access use in NPC patients. HPβCD has been administered to NPC patients with approved INDs globally since 2009.
Here we present safety, tolerability and efficacy data from 12 patients treated intravenously (IV) for over 7 years with HPβCD in the US and Brazil. Some patients subsequently received intrathecal (IT) treatment with HPβCD following on average 13 months of IV HPβCD. Several patients transitioned to an alternate HPβCD. Moderately affected NPC patients treated with HPβCD showed slowing of disease progression. Severely affected patients demonstrated periods of stability but eventually showed progression of disease. Neurologic and neurocognitive benefits were seen in most patients with IV alone, independent of the addition of IT administration. Physicians and caregivers reported improvements in quality of life for the patients on IV therapy. There were no safety issues, and the drug was well tolerated and easy to administer.
These expanded access data support the safety and potential benefit of systemic IV administration of HPβCD and provide a platform for two clinical trials to study the effect of intravenous administration of HPβCD in NPC patients.
Aim
Pulmonary hemorrhage in infancy is rare, with challenges in determining its incidence, causes, and outcomes across diverse groups. Our aim was to better understand the incidence and identified ...causes. We further analyzed the subgroup of patients meeting criteria for acute idiopathic pulmonary hemorrhage of infancy (AIPHI) to determine recurrence, mortality, and treatment.
Methods
We performed a 10‐year retrospective cohort study of infants with pulmonary hemorrhage in a large tertiary care center. One‐hundred fifty‐seven patients overall were identified.
Results
The most common diagnoses in infants with pulmonary hemorrhage were congenital heart disease (36.6%), prematurity/premature lung disease (34.6%), congenital or acquired lung disorders (15.0%), and congenital or acquired coagulopathies (13.7%). Nonaccidental trauma (NAT; n = 3) was also an important cause of pulmonary hemorrhage. All patients diagnosed with NAT had normal retinal examinations and skeletal surveys. Only four patients were identified with AIPHI. There was no mortality in this group of infants. One of four patients with AIPHI had a recurrence. Steroids were the consistent treatment for AIPHI, with a large range of treatment duration.
Conclusion
Diagnostic studies should focus on identifying non‐pulmonary sources of bleeding, infection, underlying lung disease, congenital heart defects, coagulopathies, infection, and NAT, as these were the most frequently identified causes of bleeding. NAT is not adequately identified with ophthalmology exam and skeletal survey. Overall, we found AIPHI to be a rare diagnosis. All of the patients with idiopathic hemorrhage received systemic steroids with varying doses and lengths of treatment.
Children's interstitial and diffuse lung diseases are a diverse group of rare lung disorders that present in childhood with diffuse pulmonary infiltrates and respiratory signs and symptoms. Children ...with these disorders face high morbidity and mortality and their families must cope with overwhelming uncertainty. Physicians caring for these patients are challenged by a paucity of directed therapies, or even understanding of natural history. Through the establishment of the Children's Interstitial Lung Disease Foundation Research Network and the Children's Interstitial Lung Disease Foundation significant progress has been made through collaboration and research. This review outlines the past and current successes in the new and rapidly growing field of Children's Interstitial and Diffuse Lung Disease.
Bronchiolitis obliterans (BO) is a rare, chronic form of obstructive lung disease, often initiated with injury of the bronchiolar epithelium followed by an inflammatory response and progressive ...fibrosis of small airways resulting in nonuniform luminal obliteration or narrowing. The term BO comprises a group of diseases with different underlying etiologies, courses, and characteristics. Among the better recognized inciting stimuli leading to BO are airway pathogens such as adenovirus and mycoplasma, which, in a small percentage of infected children, will result in progressive fixed airflow obstruction, an entity referred to as postinfectious bronchiolitis obliterans (PIBO). The present knowledge on BO in general is reasonably well developed, in part because of the relatively high incidence in patients who have undergone lung transplantation or bone marrow transplant recipients who have had graft-versus-host disease in the posttransplant period. The cellular and molecular pathways involved in PIBO, while assumed to be similar, have not been adequately elucidated. Since 2016, an international consortium of experts with an interest in PIBO assembles on a regular basis in Geisenheim, Germany, to discuss key areas in PIBO which include diagnostic workup, treatment strategies, and research fields.
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