Child Health and the Pediatric Pulmonology Workforce: 2020-2040.

There is concern as to whether the supply of pediatric pulmonology (PULM) subspecialists will be adequate to meet future demand. As part of an American Board of Pediatrics (ABP) Foundation-sponsored supplement investigating the future of the pediatric subspecialty workforce, this article assesses the current PULM clinical workforce and estimates the clinical workforce supply in the United States through 2040. The current workforce was assessed using ABP certification and Maintenance of Certification data, and a workforce supply model evaluating population growth, clinical effort, and geographic trends was developed after incorporating ABP data. Findings demonstrate that the number of pediatric pulmonologists has gradually increased over the past decade, and the ratio of subspecialists to children is likely to increase another 20% to 40% over the next 2 decades, although absolute numbers remain small. Geographic variation in access will persist in some regions. The proportion of women in the discipline has increased, but the proportion of pediatric pulmonologists from underrepresented in medicine backgrounds still lags behind the general population. Based on current trends, the PULM clinical workforce appears equipped to meet both population growth and the modest increase in demand for clinical services speculated to occur because of changes in the subspecialty's clinical portfolio. However, several factors could inhibit growth, and geographic maldistribution may continue to impact care access. Efforts to address variation in access and demographic diversity in the field are warranted. This article concludes by discussing the training, clinical practice, policy, and future workforce research implications of the data presented.

The Effects of Wildfire Smoke on Asthma and Allergy.

PURPOSE OF REVIEW: To review the recent literature on the effects of wildfire smoke (WFS) exposure on asthma and allergic disease, and on potential mechanisms of disease. RECENT FINDINGS: Spatiotemporal modeling and increased ground-level monitoring data are allowing a more detailed picture of the health effects of WFS exposure to emerge, especially with regard to asthma. There is also epidemiologic and some experimental evidence to suggest that WFS exposure increases allergic predisposition and upper airway or sinonasal disease, though much of the literature in this area is focused more generally on PM2.5 and is not specific for WFS. Experimental evidence for mechanisms includes disruption of epithelial integrity with downstream effects on inflammatory or immune pathways, but experimental models to date have not consistently reflected human disease in this area. Exposure to WFS has an acute detrimental effect on asthma. Potential mechanisms are suggested by in vitro and animal studies.

Obesity Is Associated with an Impaired Baseline Repertoire of Anti-Influenza Virus Antibodies.

Obesity is a risk factor for severe disease and mortality for both influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While previous studies show that individuals with obesity generate antibody responses following influenza vaccination, infection rates within the obese group were twice as high as those in the healthy-weight group. The repertoire of antibodies raised against influenza viruses following previous vaccinations and/or natural exposures is referred to here as baseline immune history (BIH). To investigate the hypothesis that obesity impacts immune memory to infections and vaccines, we profiled the BIH of obese and healthy-weight adults vaccinated with the 2010-2011 seasonal influenza vaccine in response to conformational and linear antigens. Despite the extensive heterogeneity of the BIH profiles in both groups, there were striking differences between obese and healthy subjects, especially with regard to A/H1N1 strains and the 2009 pandemic virus (Cal09). Individuals with obesity had lower IgG and IgA magnitude and breadth for a panel of A/H1N1 whole viruses and hemagglutinin proteins from 1933 to 2009 but increased IgG magnitude and breadth for linear peptides from the Cal09 H1 and N1 proteins. Age was also associated with A/H1N1 BIH, with young individuals with obesity being more likely to have reduced A/H1N1 BIH. We found that individuals with low IgG BIH had significantly lower neutralizing antibody titers than individuals with high IgG BIH. Taken together, our findings suggest that increased susceptibility of obese participants to influenza infection may be mediated in part by obesity-associated differences in the memory B-cell repertoire, which cannot be ameliorated by current seasonal vaccination regimens. Overall, these data have vital implications for the next generation of influenza virus and SARS-CoV-2 vaccines. IMPORTANCE Obesity is associated with increased morbidity and mortality from influenza and SARS-CoV-2 infection. While vaccination is the most effective strategy for preventing influenza virus infection, our previous studies showed that influenza vaccines fail to provide optimal protection in obese individuals despite reaching canonical correlates of protection. Here, we show that obesity may impair immune history in humans and cannot be overcome by seasonal vaccination, especially in younger individuals with decreased lifetime exposure to infections and seasonal vaccines. Low baseline immune history is associated with decreased protective antibody responses. Obesity potentially handicaps overall responses to vaccination, biasing it toward responses to linear epitopes, which may reduce protective capacity. Taken together, our data suggest that young obese individuals are at an increased risk of reduced protection by vaccination, likely due to altered immune history biased toward nonprotective antibody responses. Given the worldwide obesity epidemic coupled with seasonal respiratory virus infections and the inevitable next pandemic, it is imperative that we understand and improve vaccine efficacy in this high-risk population. The design, development, and usage of vaccines for and in obese individuals may need critical evaluation, and immune history should be considered an alternate correlate of protection in future vaccine clinical trials.

Development of a screening protocol to identify persons who are responsive to wood smoke particle-induced airway inflammation with pilot assessment of GSTM1 genotype and asthma status as response modifiers.

BACKGROUND: We are currently screening human volunteers to determine their sputum polymorphonuclear neutrophil (PMN) response 6- and 24-hours following initiation of exposure to wood smoke particles (WSP). Inflammatory responders (≥10% increase in %PMN) are identified for their subsequent participation in mitigation studies against WSP-induced airways inflammation. In this report we compared responder status (<i>N</i> = 52) at both 6 and 24 hr time points to refine/expand its classification, assessed the impact of the GSTM1 genotype, asthma status and sex on responder status, and explored whether sputum soluble phase markers of inflammation correlate with PMN responsiveness to WSP. RESULTS: Six-hour responders tended to be 24-hour responders and vice versa, but 24-hour responders also had significantly increased IL-1beta, IL-6, IL-8 at 24 hours post WSP exposure. The GSTM1 null genotype significantly (<i>p</i> &lt; 0.05) enhanced the %PMN response by 24% in the 24-hour responders and not at all in the 6 hours responders. Asthma status enhanced the 24 hour %PMN response in the 6- and 24-hour responders. In the entire cohort (not stratified by responder status), we found a significant, but very small decrease in FVC and systolic blood pressure immediately following WSP exposure and sputum %PMNs were significantly increased and associated with sputum inflammatory markers (IL-1beta, IL-6, IL-8, and PMN/mg) at 24 but not 6 hours post exposure. Blood endpoints in the entire cohort showed a significant increase in %PMN and PMN/mg at 6 but not 24 hours. Sex had no effect on %PMN response. CONCLUSIONS: The 24-hour time point was more informative than the 6-hour time point in optimally and expansively defining airway inflammatory responsiveness to WSP exposure. GSTM1 and asthma status are significant effect modifiers of this response. These study design and subject parameters should be considered before enrolling volunteers for proof-of-concept WSP mitigation studies.

Obesity is associated with an altered baseline and post-vaccination influenza antibody repertoire.

As highlighted by the ongoing COVID-19 pandemic, vaccination is critical for infectious disease prevention and control. Obesity is associated with increased morbidity and mortality from respiratory virus infections. While obese individuals respond to influenza vaccination, what is considered a seroprotective response may not fully protect the global obese population. In a cohort vaccinated with the 2010-2011 trivalent inactivated influenza vaccine, baseline immune history and vaccination responses were found to significantly differ in obese individuals compared to healthy controls, especially towards the 2009 pandemic strain of A/H1N1 influenza virus. Young, obese individuals displayed responses skewed towards linear peptides versus conformational antigens, suggesting aberrant obese immune response. Overall, these data have vital implications for the next generation of influenza vaccines, and towards the current SARS-CoV-2 vaccination campaign.

Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. A Clinical Trial.

Inhalation of tobacco smoke has been linked to increased risk of viral infection, such as influenza. Inhalation of electronic-cigarette (e-cigarette) aerosol has also recently been linked to immune suppression within the respiratory tract, specifically the nasal mucosa. We propose that changes in the nasal mucosal immune response modify antiviral host-defense responses in e-cigarette users. Nonsmokers, cigarette smokers, and e-cigarette users were inoculated with live-attenuated influenza virus (LAIV) to safely examine the innate immune response to influenza infection. Before and after LAIV inoculation, we collected nasal epithelial-lining fluid, nasal lavage fluid, nasal-scrape biopsy specimens, urine, and blood. Endpoints examined include cytokines and chemokines, influenza-specific IgA, immune-gene expression, and markers of viral load. Statistical analysis included primary comparisons of cigarette and e-cigarette groups with nonsmokers, as well as secondary analysis of demographic factors as potential modifiers. Markers of viral load did not differ among the three groups. Nasal-lavage-fluid anti-LAIV IgA levels increased in nonsmokers after LAIV inoculation but did not increase in e-cigarette users and cigarette smokers. LAIV-induced gene-expression changes in nasal biopsy specimens differed in cigarette smokers and e-cigarette users as compared with nonsmokers, with a greater number of genes changed in e-cigarette users, mostly resulting in decreased expression. The top downregulated genes in cigarette smokers were SMPD3, NOS2A, and KLRB1, and the top downregulated genes in e-cigarette users were MR1, NT5E, and HRAS. Similarly, LAIV-induced cytokine levels in nasal epithelial-lining fluid differed among the three groups, including decreased antiviral host-defense mediators (IFNγ, IL6, and IL12p40). We also detected that sex interacted with tobacco-product exposure to modify LAIV-induced immune-gene expression. Our results demonstrate that e-cigarette use altered nasal LAIV-induced immune responses, including gene expression, cytokine and chemokine release, and LAIV-specific IgA levels. Together, these data suggest that e-cigarette use induces changes in the nasal mucosa that are consistent with the potential for altered respiratory antiviral host-defense function.Clinical trial registered with www.clinicaltrials.gov (NCT02019745).

The roles of a pediatric pulmonologist during the COVID-19 pandemic.

Pediatric pulmonologists have been involved in the care of adult COVID-19 patients in a variety of ways, particularly in areas with a high concentration of cases. This invited commentary is a series of questions to Dr Mikhail Kazachkov, a pediatric pulmonologist at New York University, about his experiences to date in a major COVID-19 "hotspot" and his thoughts about how other pediatric pulmonologists facing this situation can best support their colleagues.

A proposal for the addressing the needs of the pediatric pulmonary work force.

Unprecedented opportunities and daunting difficulties are anticipated in the future of pediatric pulmonary medicine. To address these issues and optimize pediatric pulmonary training, a group of faculty from various institutions met in 2019 and proposed specific, long-term solutions to the emerging problems in the field. Input on these ideas was then solicited more broadly from faculty with relevant expertise and from recent trainees. This proposal is a synthesis of these ideas. Pediatric pulmonology was among the first pediatric specialties to be grounded deliberately in science, requiring its fellows to demonstrate expertise in scientific inquiry (1). In the future, we will need more training in science, not less. Specifically, the scope of scientific inquiry will need to be broader. The proposal outlined below is designed to help optimize the practices of current providers and to prepare the next generation to be leaders in pediatric care in the future. We are optimistic that this can be accomplished. Our broad objectives are (a) to meet the pediatric subspecialty workforce demand by increasing interest and participation in pediatric pulmonary training; (b) to modernize training to ensure that future pediatric pulmonologists will be prepared clinically and scientifically for the future of the field; (c) to train pediatric pulmonologists who will add value in the future of pediatric healthcare, complemented by advanced practice providers and artificial intelligence systems that are well-informed to optimize quality healthcare delivery; and (d) to decrease the cost and improve the quality of care provided to children with respiratory diseases.

Pediatric Pulmonology Year in Review 2018: Rare lung disease, neuromuscular disease, and diagnostic testing.

Pediatric Pulmonology publishes original research, case reports, and review articles on topics related to a wide range of children's respiratory disorders. In this article, we highlight the past year's publications in the topic areas of rare lung diseases, respiratory complications of neuromuscular disorders, and diagnostic testing, as well as selected literature in these areas from other journals.

Pediatric Pulmonology year in review 2018: Asthma, physiology/pulmonary function testing, and respiratory infections.

Pediatric Pulmonology publishes original research, reviews, and case reports related to a wide range of children's respiratory disorders. In our "Year in Review" series, we summarize publications in our major topic areas from 2018, in the context of selected literature in these areas from other journals relevant to our discipline. This review covers selected articles on asthma, physiology/lung function testing, and respiratory infections.

Wood Smoke Exposure Alters Human Inflammatory Responses to Viral Infection in a Sex-Specific Manner. A Randomized, Placebo-controlled Study.

RATIONALE: Exposure to particulates from burning biomass is an increasing global health issue. Burning biomass, including wood smoke, is associated with increased lower respiratory infections. OBJECTIVES: To determine whether acute exposure to wood smoke modifies nasal inflammatory responses to influenza. METHODS: Healthy young adults (n = 39) were randomized to a 2-hour controlled chamber exposure to wood smoke, where exposure levels were controlled to particulate number (wood smoke particles [WSP]; 500 µg/cm3) or filtered air, followed by nasal inoculation with a vaccine dose of live attenuated influenza virus (LAIV). Nasal lavage was performed before exposure (Day 0) and on Days 1 and 2 after exposure. Nasal lavage fluid cells were analyzed for inflammatory gene expression profiles, and cell-free fluid was assayed for cytokines. MEASUREMENTS AND MAIN RESULTS: Only IP-10 protein levels were affected, suppressed, by WSP exposure in aggregate analysis. Subsequent analysis indicated an exposure × sex interaction, prompting additional analyses of WSP- and LAIV-induced changes in males and females. Inflammation-related gene expression profiles differed between the sexes, at baseline (males greater than females), after LAIV inoculation (females greater than males), and after WSP exposure (increase in males and decrease in females), demonstrating that WSP- and LAIV-induced changes in antiviral defense responses in the nasal mucosa occur in a sex-specific manner. CONCLUSIONS: WSP exposure resulted in minimal modification of LAIV-induced responses in aggregate analysis. In contrast, analyzing WSP-induced modification of LAIV responses in the sexes separately unmasked sex-specific differences in response to exposure. These data highlight the need for additional studies to understand sex-specific pollutant-induced effects. Clinical trial registered with www.clinicaltrials.gov (NCT02183753).

Pediatric pulmonology year in review 2017: Part 1.

Pediatric Pulmonology publishes original research, case reports and review articles on topics related to a wide range of children's respiratory disorders. In this article (Part 1 of a series), we summarize the past year's publications in our major topic areas, as well as selected literature in these areas from other journals. In Part 1, we review selected articles on diagnostic testing/endoscopy, respiratory complications of neuromuscular disorders, and rare lung diseases.

Pediatric Pulmonology year in review 2017: Part 3.

Pediatric Pulmonology publishes original research, reviews, and case reports related to a wide range of children's respiratory disorders. We here summarize the past year's publications in our major topic areas, in the context of selected literature in these areas from other journals relevant to our discipline. This review (Part 3 of a 5-part series) covers selected articles on asthma, physiology/lung function testing, and respiratory infections.

Pediatric pulmonology year in review 2017: Part 4 (Sleep medicine).

Pediatric Pulmonology publishes original research, case reports and review articles on topics related to a wide range of children's respiratory disorders. In this article (Part 4 of a 5-part series), we summarize the past year's publications in sleep medicine, in the context of selected literature in this area from other journals. Articles are highlighted on topics including diagnosis and treatment of OSAS, sleep duration and position, and sleep disorders in chronic disease.

Worsening anxiety and depression after initiation of lumacaftor/ivacaftor combination therapy in adolescent females with cystic fibrosis.

In both phase III studies of LUM/IVA, as well as an extension study, worsening of mental health was not reported as a common side effect. Here we describe five cases in adolescent female patients that suggest a worsening of anxiety or depression associated with its use. In these five patients, two experienced suicidal ideation and three made suicide attempts that resulted in psychiatric hospitalizations.

Pediatric Pulmonology year in review 2016: Part 1.

Pediatric Pulmonology continues to publish research and clinical topics related to the entire range of children's respiratory disorders. As we have done annually in recent years, we here summarize the past year's publications in our major topic areas, as well as selected literature in these areas from other core journals relevant to our discipline. This review (Part 1) covers selected articles on sleep, diagnostic testing/endoscopy, respiratory complications of neuromuscular disorders, and rare lung diseases.