Abstract
1982–84
The start of my pediatric allergy and asthma specialist career was in the early 1980’s. Fortunately, the allowance for a positive test for FEV1 (Forced expiratory volume in one second) change after a bronchodilator on a standard spirometry was 12%, but being in a mostly adult-based fellowship the opportunity to see children younger than early adolescence was minimal, and spirometry for K-8 children was severely limited. Preschool children with wheezing were a black box. At that time, the requirement for adequate pediatric-based experience was more flexible, and most of the fellows that had preceded me were Internal Medicine trained. Pediatrics was an outlier!
The holy grail for our fellowship, and at a few other centers across the country, was the search for the cause of airway hyperresponsiveness (AHR). This was examined using methacholine, cold air, hypertonic saline, distilled water, and eucapnic hyperventilation. The genetic component of asthma was limited to twin studies. An extensive analysis of allergic disease in twins came from this combination of AHR research and twins. 1
Using the different measures of determining AHR, especially with methacholine, allowed for the examination of thousands of methacholine-based challenges, and hundreds of cold air or distilled water challenges and antigen challenges. It was clear that methacholine responsiveness measured more than just asthma, but in an asthmatic the response was swift and dramatic. Fortunately, easily reversed. A cold air or distilled water bronchospasm response was only seen in asthmatics, and on a few occasions invoked a late asthmatic response, although these late reactions were previously unknown to occur expect in antigen challenge. Surprisingly, late reactions in antigen challenges are difficult to invoke, a problem when a drug study was intended to modify the late asthmatic response.
Asthma was asthma, and the program director would ask if I was a “lumper” or a “splitter,” now referred to as asthma phenotypes. Any preschool child with recurrent wheezing was an enigma, and not until the seminal work of Fernando Martinez did it make more sense. 2 My pediatric background allowed for a vague sense of post-respiratory syncytial virus wheeze, but in a less understood way. Nebulizing Cromolyn 4x a day became quite unbearable!
At that point there was no Abbas (Cellular and Molecular Immunology, Abbas), and would not be for another 8 years!
Preparing for career in academic medicine: the start
Determine the Commitment to Pediatric Allergy, Asthma, and Immunology by the Pediatric chairperson. Find a seasoned mentor. Write grants. Court referrals internally and externally Present to Ground Rounds any Fellowship emphasis or research. Join a national and local Allergy organizations and apply to a committee. Build collaboration in other specialties.
Building on the data set of the previously NIH-sponsored studies of asthma and bronchial reactivity I worked on during Fellowship, I was able to extend the research under my own auspices with a young investigator grant from NIH. Over the next 5 years of the grant, the Center for Family Asthma research at Creighton University had over 20 publications on asthma in families and bronchoprovocation testing under the mentorship of the Allergy and Asthma faculty headed by Dr. Robert Townley
In addition to starting the Pediatric Allergy and Asthma clinic at Creighton University School of Medicine, I was fortunate to start collaborating with the new Pediatric Chairman, Dr. James Cassidy. Working as his associate in the Pediatric Rheumatology Clinic, another avenue of medical care was added. We had an additional 6 manuscripts in the Rheumatology field, including seminal work of bone density in both juvenile arthritis and also pediatric asthma,3,4 collaborating with internationally recognized adult bone density specialists at Creighton University. The American Academy of Allergy and Immunology provided a location for abstract presentation, and work on the Genetic and Bronchoprovocation Committees.
Mid-Career recommendations
Maintain grant support when available. Continue with other collaborators for publications. Find a niche Allergy and Immunology or asthma field(s). Present locally, regionally, and nationally. Author case-reports and reviews with junior faculty and learners.
The turning point in my career came with the request for proposal (RFP) from NIH for a grant on “Genetics of Asthma.” The application requested a sample family asthma approach application to determine “serious” centers, but after the selection, the awardees would collaborate on a final grant plan. Realizing the cumbersome structure of family studies, having been part of family studies for 10 years,
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my genetic collaborator and I submitted a sib-sib analysis strategy. Needless to say, our grant was not accepted, and after the awardees reconvened, a sib-sib analysis approach was initiated!
At that point, my attention turned to expanding my asthma and allergy practice, maintaining my rheumatology connection although Dr. Cassidy had left our department, and starting a focus on food allergy, food challenges, high-risk inner city pediatric asthma, and chronic pediatric sinusitis. The initial eosinophilic esophagitis (EoE) patient, an adolescent female, presented in 1999. A new niche was opened!
Publications during this period were across multiple fields and with senior and junior faculty and learners. From the end of the NIH grant to the entry into EoE publications, over 40 publications were accepted, including research on Bacillus Calmette-Guérin, reviews on infant wheezing, and a Vitamin D study in asthmatic children, a very early look in that field. 6 An interview in Pediatric Asthma, Immunology, and Pulmonary in 2006 predated this current retrospective on an academic career. 7
Notably, an initiative by the allergy community in Nebraska led to the nation’s first state-wide mandate for stock epinephrine and albuterol for anaphylaxis and asthma emergencies for all Nebraska schools. This effort was summarized in a publication in 2006. 8
Recommendations for senior academic Allergy-Immunology physicians
Hire the next generation of Pediatric Allergy-Specialists. Become a mentor. Maintain grant funding or special niche practice areas. Maintain publication, often in national or international guidelines or practice management programs. Find new niches for academic simulation and improvement of patient care. Develop divisional or department leadership positions.
The emergence of eosinophilic esophagitis patients in the pediatric gastrointestinal arena allowed for the development of a Pediatric EoE multidimensional clinic in Omaha, to serve a large catchment area. Over a 25-year period, 3 different pediatric gastroenterologists, nurses, and dietary support joined me in a EoE clinic (now Eosinophilic Gastrointestinal Disease Clinic). Emerging from that niche has been 11 eosinophilic esophagitis publications, including an international consensus article and a multi-center study of EoE hereditability.9,10 Included, also, in the work on the EGID committee at the AAAAI a lead authorship on slide sets for EoE and EGID diseases, with current revision on-line.
A comment from my fellowship director that “significant improvement in FVC (Forced vital capacity) after a bronchodilator is a strong indication for asthma” sat on a shelf in my brain for 25+ years. Coupled with the frequent comment that the FEF25-75 (Forced expiratory flow from 25% to 75% of total volume) was “too” variable to be considered, became rallying points for my reconsideration of spirometry interpretation, especially in the population of difficult to control asthmatics and the introduction of biologics for asthma. Several publications induced an abrupt rethinking of the information in the standard spirometry and how the data could be used in clinical practice.11,12
The publications from Simon et al.,
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Sorkness et al.,
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and Szefler
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found an intersection for me in z-score determination, small airway measures and FEV1 disability, coupled with a change in FVC of 10% or greater. This allowed a deep dive into the data presented in a properly prepared spirometry. A summary of those changes in spirometry interpretation are as follows:
A change in FVC of 10% or greater after bronchodilator demonstrates a movement of trapped lung volume airways that were inaccessible to the baseline forced vital capacity. With the simultaneous improvement in FEV1 and FEF25-75, this previously trapped lung volume come from lung volume beyond the level of the airway generations expressed by the FEF25-75. The improvement in FEV1 of 10% is very reasonable to show significant airway reversibility, but data published in children prior to the ATS revision of 12% to 10% FEV1 change strongly suggested that an 8% improvement in FEV1 after bronchodilator was beyond what could be expected in an non-asthmatic child.
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The FEF25-75 data should be considered as informational. If it has a proportional rise after bronchodilator to the FEV1 rise, thus suggesting that when a reasonable expiratory time is produced, that the FEF25-75 airflow change happens after the FEV1 is completed. The term “small airway” may not be totally correct, but “smaller” airway change is likely relevant. The other situation seen on occasion is that the FEV1 changes <8% but the FEF25-75 changes to a degree not likely by chance. Limited data suggests this may be a marker for cough variant asthma.
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Regardless, the FEF25-75 has applicability in making clinical decisions.
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These observations require being well versed in all statistical aspects of spirometry, including z-scores, and the recommendations from the national and international societies.
In addition to the more refined approach to the standard spirometry, it is critical for asthma specialists to have the availability of exhaled nitric oxide testing. 19 Whether to assess the role of high type-2 asthma phenomenon, necessity of inhaled corticosteroids, and compliance/dosing considerations, a nitric oxide measurement is necessary for effective care.
The final piece of high-level academic asthma management is the potential for measuring lung function in preschool children using impulse oscillometry (IOS).20,21 Becoming a next generation measure, both in young and older children, the information from an IOS test, using bronchodilators, is to prove large and small airway (down to the terminal bronchioles) reversibility and allows serial measures of effectiveness and compliance. The care of asthmatic children before age 5–6 years, when spirometry can be a generally measured, was largely clinical prior to IOS testing. IOS provides objective information allowing more precise standard of care for the preschool wheezing child. 20 In the severe asthmatic older child, IOS provides a window into the small airway function, and improves step-up care decisions.
Conclusion
An academic career spanning 4 decades has seen the evolution of asthma care from theophylline and 4 times a day inhaled steroids, to single day-dose asthma inhalers and biologics. The old standby of spirometry has been constant, with changes, such as the reduction in percent FEV1 change to be significant, which is more realistic to patient decision-making. Newer concepts of high TH2 asthma or low TH2 asthma echo the intrinsic versus extrinsic concepts of old. Our understanding of asthma and asthma therapy have evolved, but asthma is complex and requires constant diligence of both the provider and their patients for maximal benefit. This is best reflected in current concepts of asthma remission after the initiation of biologics, again revealing the changing nature of current asthma care concepts. 22
Footnotes
Acknowledgments
The author wishes to acknowledge the mentorship of Drs. Robert Townley and James Cassidy and more recently the collaboration of Drs. M Pasha, Mark Wilson and Michael Cooperstock.
Author Disclosure Statement
No competing financial interests exist.
Funding Information
No funding was received for this article.