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1. Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations

Author

Szczesny, Brooke, Boorgula, Meher Preethi, Chavan, Sameer, Campbell, Monica, Johnson, Randi K., Kammers, Kai, Thompson, Emma E., Cox, Madison S., Shankar, Gautam, Cox, Corey, Morin, Andréanne, Lorizio, Wendy, Daya, Michelle, Kelada, Samir N. P., Beaty, Terri H., Doumatey, Ayo P., Cruz, Alvaro A., Watson, Harold, Naureckas, Edward T., Giles, B. Louise, Arinola, Ganiyu A., Sogaolu, Olumide, Falade, Adegoke G., Hansel, Nadia N., Yang, Ivana V., Olopade, Christopher O., Rotimi, Charles N., Landis, R. Clive, Figueiredo, Camila A., Altman, Matthew C., Kenny, Eimear, Ruczinski, Ingo, Liu, Andrew H., Ober, Carole, Taub, Margaret A., Barnes, Kathleen C., and Mathias, Rasika A.

Published
2024
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2. Home and school pollutant exposure, respiratory outcomes, and influence of historical redlining

Author

Jung, Kyung Hwa, Argenio, Kira L., Jackson, Daniel J., Miller, Rachel L., Perzanowski, Matthew S., Rundle, Andrew G., Bacharier, Leonard B., Busse, William W., Cohen, Robyn T., Visness, Cynthia M., Gill, Michelle A., Gruchalla, Rebecca S., Hershey, Gurjit K., Kado, Rachel K., Sherenian, Michael G., Liu, Andrew H., Makhija, Melanie M., Pillai, Dinesh K., Rivera-Spoljaric, Katherine, Gergen, Peter J., Altman, Matthew C., Sandel, Megan T., Sorkness, Christine A., Kattan, Meyer, and Lovinsky-Desir, Stephanie

Published
2024
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3. A pediatric randomized, controlled trial of German cockroach subcutaneous immunotherapy

Author

Zoratti, Edward, Wood, Robert, Pomés, Anna, Da Silva Antunes, Ricardo, Altman, Matthew C., Benson, Basilin, Wheatley, Lisa M., Cho, Kate, Calatroni, Agustin, Little, Frederic F., Pongracic, J., Makhija, Melanie, Khurana Hershey, Gurjit K., Sherenian, Michael G., Rivera-Spoljaric, Katherine, Stokes, Jeffrey R., Gill, Michelle A., Gruchalla, Rebecca S., Chambliss, Jeffrey, Liu, Andrew H., Kattan, Meyer, Busse, Paula J., Bacharier, Leonard B., Sheehan, William, Kim, Haejin., Glesner, Jill, Gergen, Peter J., Togias, Alkis, Baucom, Jessica L., Visness, Cynthia M., Sette, Alessandro, Busse, William W., and Jackson, Daniel J.

Published
2024
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4. Activated sputum eosinophils associated with exacerbations in children on mepolizumab

Author

Wilson, Gabriella E., Knight, James, Liu, Qing, Shelar, Ashish, Stewart, Emma, Wang, Xiaomei, Yan, Xiting, Sanders, Joshua, Visness, Cynthia, Gill, Michelle, Gruchalla, Rebecca, Liu, Andrew H., Kattan, Meyer, Khurana Hershey, Gurjit K., Togias, Alkis, Becker, Patrice M., Altman, Matthew C., Busse, William W., Jackson, Daniel J., Montgomery, Ruth R., and Chupp, Geoffrey L.

Published
2024
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5. Gene-based association study of rare variants in children of diverse ancestries implicates TNFRSF21 in the development of allergic asthma

Author

Clay, Selene, Alladina, Jehan, Smith, Neal P., Visness, Cynthia M., Wood, Robert A., O’Connor, George T., Cohen, Robyn T., Khurana Hershey, Gurjit K., Kercsmar, Carolyn M., Gruchalla, Rebecca S., Gill, Michelle A., Liu, Andrew H., Kim, Haejin, Kattan, Meyer, Bacharier, Leonard B., Rastogi, Deepa, Rivera-Spoljaric, Katherine, Robison, Rachel G., Gergen, Peter J., Busse, William W., Villani, Alexandra-Chloe, Cho, Josalyn L., Medoff, Benjamin D., Gern, James E., Jackson, Daniel J., Ober, Carole, and Dapas, Matthew

Published
2024
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6. The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: An overview of Network organization, procedures, and interventions

Author

Georas, Steve N, Wright, Rosalind J, Ivanova, Anastasia, Israel, Elliot, LaVange, Lisa M, Akuthota, Praveen, Carr, Tara F, Denlinger, Loren C, Fajt, Merritt L, Kumar, Rajesh, O’Neal, Wanda K, Phipatanakul, Wanda, Szefler, Stanley J, Aronica, Mark A, Bacharier, Leonard B, Burbank, Allison J, Castro, Mario, Alexander, Laura Crotty, Bamdad, Julie, Cardet, Juan Carlos, Comhair, Suzy AA, Covar, Ronina A, DiMango, Emily A, Erwin, Kim, Erzurum, Serpil C, Fahy, John V, Gaffin, Jonathan M, Gaston, Benjamin, Gerald, Lynn B, Hoffman, Eric A, Holguin, Fernando, Jackson, Daniel J, James, John, Jarjour, Nizar N, Kenyon, Nicholas J, Khatri, Sumita, Kirwan, John P, Kraft, Monica, Krishnan, Jerry A, Liu, Andrew H, Liu, Mark C, Marquis, M Alison, Martinez, Fernando, Mey, Jacob, Moore, Wendy C, Moy, James N, Ortega, Victor E, Peden, David B, Pennington, Emily, Peters, Michael C, Ross, Kristie, Sanchez, Maria, Smith, Lewis J, Sorkness, Ronald L, Wechsler, Michael E, Wenzel, Sally E, White, Steven R, Zein, Joe, Zeki, Amir A, Noel, Patricia, Billheimer, Dean, Bleecker, Eugene R, Branch, Emily, Conway, Michelle, Daines, Cori, Deaton, Isaac, Evans, Alexandria, Field, Paige, Francisco, Dave, Hastie, Annette T, Hmieleski, Bob, Krings, Jeffrey O, Liu, Yanqin, Merchen, Janell L, Meyers, Deborah A, Narendran, Nirushan, Peters, Stephen P, Pippins, Anna, Rank, Matthew A, Schunk, Ronald, Skeps, Raymond, Wright, Benjamin, Banzon, Tina M, Bartnikas, Lisa M, Baxi, Sachin N, Betapudi, Vishwanath, Brick, Isabelle, Brockway, Conor, Casale, Thomas B, Castillo-Ruano, Kathleen, Cinelli, Maria Angeles, Crestani, Elena, Cunningham, Amparito, Day-Lewis, Megan, Diaz-Cabrera, Natalie, DiMango, Angela, Esty, Brittany, Fandozzi, Eva, Fernandez, Jesse, and Fitzpatrick, Elizabeth

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Lung, Precision Medicine, Asthma, Clinical Trials and Supportive Activities, Respiratory, Good Health and Well Being, Advisory Committees, Biomarkers, Clinical Protocols, Clinical Trials, Phase II as Topic, Humans, Research Design, Severity of Illness Index, Tomography, X-Ray Computed, Severe asthma, precision medicine, adaptive clinical trial design, asthma exacerbation, type 2 asthma, non-type 2 asthma, patient advisory committee, biomarker, PrecISE Study Team, non–type 2 asthma, Immunology, Allergy
Abstract

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here, we describe the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the United States. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma, and is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the PrecISE Network will evaluate up to 6 interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the PrecISE Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for severe asthma.

Published
2022

10. PrecISE: Precision Medicine in Severe Asthma: An adaptive platform trial with biomarker ascertainment

Author

Israel, Elliot, Denlinger, Loren C, Bacharier, Leonard B, LaVange, Lisa M, Moore, Wendy C, Peters, Michael C, Georas, Steve N, Wright, Rosalind J, Mauger, David T, Noel, Patricia, Akuthota, Praveen, Bach, Julia, Bleecker, Eugene R, Cardet, Juan Carlos, Carr, Tara F, Castro, Mario, Cinelli, Angeles, Comhair, Suzy AA, Covar, Ronina A, Alexander, Laura Crotty, DiMango, Emily A, Erzurum, Serpil C, Fahy, John V, Fajt, Merritt L, Gaston, Benjamin M, Hoffman, Eric A, Holguin, Fernando, Jackson, Daniel J, Jain, Sonia, Jarjour, Nizar N, Ji, Yuan, Kenyon, Nicholas J, Kosorok, Michael R, Kraft, Monica, Krishnan, Jerry A, Kumar, Rajesh, Liu, Andrew H, Liu, Mark C, Ly, Ngoc P, Marquis, M Alison, Martinez, Fernando D, Moy, James N, O'Neal, Wanda K, Ortega, Victor E, Peden, David B, Phipatanakul, Wanda, Ross, Kristie, Smith, Lewis J, Szefler, Stanley J, Teague, W Gerald, Tulchinsky, Abigail F, Vijayanand, Pandurangan, Wechsler, Michael E, Wenzel, Sally E, White, Steven R, Zeki, Amir A, and Ivanova, Anastasia

Subjects
Biomedical and Clinical Sciences, Immunology, Clinical Research, Biotechnology, Lung, Clinical Trials and Supportive Activities, Asthma, Respiratory, Good Health and Well Being, Biomarkers, Humans, Precision Medicine, Randomized Controlled Trials as Topic, Research Design, Severe asthma, therapy, clinical trial, biomarkers, precision medicine, adaptive design, master protocol, platform trial, Allergy
Abstract

Severe asthma accounts for almost half the cost associated with asthma. Severe asthma is driven by heterogeneous molecular mechanisms. Conventional clinical trial design often lacks the power and efficiency to target subgroups with specific pathobiological mechanisms. Furthermore, the validation and approval of new asthma therapies is a lengthy process. A large proportion of that time is taken by clinical trials to validate asthma interventions. The National Institutes of Health Precision Medicine in Severe and/or Exacerbation Prone Asthma (PrecISE) program was established with the goal of designing and executing a trial that uses adaptive design techniques to rapidly evaluate novel interventions in biomarker-defined subgroups of severe asthma, while seeking to refine these biomarker subgroups, and to identify early markers of response to therapy. The novel trial design is an adaptive platform trial conducted under a single master protocol that incorporates precision medicine components. Furthermore, it includes innovative applications of futility analysis, cross-over design with use of shared placebo groups, and early futility analysis to permit more rapid identification of effective interventions. The development and rationale behind the study design are described. The interventions chosen for the initial investigation and the criteria used to identify these interventions are enumerated. The biomarker-based adaptive design and analytic scheme are detailed as well as special considerations involved in the final trial design.

Published
2021

11. Associations between outdoor air pollutants and non-viral asthma exacerbations and airway inflammatory responses in children and adolescents living in urban areas in the USA: a retrospective secondary analysis

Author

Altman, Matthew C, Kattan, Meyer, O'Connor, George T, Murphy, Ryan C, Whalen, Elizabeth, LeBeau, Petra, Calatroni, Agustin, Gill, Michelle A, Gruchalla, Rebecca S, Liu, Andrew H, Lovinsky-Desir, Stephanie, Pongracic, Jacqueline A, Kercsmar, Carolyn M, Khurana Hershey, Gurjit K, Zoratti, Edward M, Teach, Stephen J, Bacharier, Leonard B, Wheatley, Lisa M, Sigelman, Steve M, Gergen, Peter J, Togias, Alkis, Busse, William W, Gern, James E, and Jackson, Daniel J

Published
2023
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13. Distinct nasal airway bacterial microbiotas differentially relate to exacerbation in pediatric patients with asthma

Author

McCauley, Kathryn, Durack, Juliana, Valladares, Ricardo, Fadrosh, Douglas W, Lin, Din L, Calatroni, Agustin, LeBeau, Petra K, Tran, Hoang T, Fujimura, Kei E, LaMere, Brandon, Merana, Geil, Lynch, Kole, Cohen, Robyn T, Pongracic, Jacqueline, Hershey, Gurjit K Khurana, Kercsmar, Carolyn M, Gill, Michelle, Liu, Andrew H, Kim, Haejin, Kattan, Meyer, Teach, Stephen J, Togias, Alkis, Boushey, Homer A, Gern, James E, Jackson, Daniel J, Lynch, Susan V, and Consortium, Institute of Allergy and Infectious Diseases–sponsored Inner-City Asthma

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Lung, Asthma, Clinical Research, Pediatric, Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, 2.2 Factors relating to the physical environment, Infection, Respiratory, A549 Cells, Adolescent, Cell Death, Child, Disease Progression, Eosinophils, Female, Humans, Infant, Inflammation, Male, Microbiota, Nasal Mucosa, RNA, Ribosomal, 16S, Respiratory System, Respiratory Tract Infections, Moraxella species, Staphylococcus species, 16S rRNA, airway, asthma, exacerbation, rhinovirus, National Institute of Allergy and Infectious Diseases–sponsored Inner-City Asthma Consortium, Immunology, Allergy
Abstract

BackgroundIn infants, distinct nasopharyngeal bacterial microbiotas differentially associate with the incidence and severity of acute respiratory tract infection and childhood asthma development.ObjectiveWe hypothesized that distinct nasal airway microbiota structures also exist in children with asthma and relate to clinical outcomes.MethodsNasal secretion samples (n = 3122) collected after randomization during the fall season from children with asthma (6-17 years, n = 413) enrolled in a trial of omalizumab (anti-IgE) underwent 16S rRNA profiling. Statistical analyses with exacerbation as the primary outcome and rhinovirus infection and respiratory illnesses as secondary outcomes were performed. Using A549 epithelial cells, we assessed nasal isolates of Moraxella, Staphylococcus, and Corynebacterium species for their capacity to induce epithelial damage and inflammatory responses.ResultsSix nasal airway microbiota assemblages, each dominated by Moraxella, Staphylococcus, Corynebacterium, Streptococcus, Alloiococcus, or Haemophilus species, were observed. Moraxella and Staphylococcus species-dominated microbiotas were most frequently detected and exhibited temporal stability. Nasal microbiotas dominated by Moraxella species were associated with increased exacerbation risk and eosinophil activation. Staphylococcus or Corynebacterium species-dominated microbiotas were associated with reduced respiratory illness and exacerbation events, whereas Streptococcus species-dominated assemblages increased the risk of rhinovirus infection. Nasal microbiota composition remained relatively stable despite viral infection or exacerbation; only a few taxa belonging to the dominant genera exhibited relative abundance fluctuations during these events. In vitro, Moraxella catarrhalis induced significantly greater epithelial damage and inflammatory cytokine expression (IL-33 and IL-8) compared with other dominant nasal bacterial isolates tested.ConclusionDistinct nasal airway microbiotas of children with asthma relate to the likelihood of exacerbation, rhinovirus infection, and respiratory illnesses during the fall season.

Published
2019

14. Correction to: Dual RNA-seq reveals viral infections in asthmatic children without respiratory illness which are associated with changes in the airway transcriptome

Author

Wesolowska-Andersen, Agata, Everman, Jamie L, Davidson, Rebecca, Rios, Cydney, Herrin, Rachelle, Eng, Celeste, Janssen, William J, Liu, Andrew H, Oh, Sam S, Kumar, Rajesh, Fingerlin, Tasha E, Rodriguez-Santana, Jose, Burchard, Esteban G, and Seibold, Max A

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Clinical Research, Lung, Genetics, Environmental Sciences, Information and Computing Sciences, Bioinformatics
Abstract

In our recent article [1], it has come to our attention that the sample labels are not consistent between Table 1, the data labels deposited in the Sequence Read Archive, and Additional file 1: Table S2. We are therefore providing an updated Additional file 1: Table S2 so identical samples now have the same label.

Published
2018

15. Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial

Author

Jackson, Daniel J, Bacharier, Leonard B, Gergen, Peter J, Gagalis, Lisa, Calatroni, Agustin, Wellford, Stephanie, Gill, Michelle A, Stokes, Jeffrey, Liu, Andrew H, Gruchalla, Rebecca S, Cohen, Robyn T, Makhija, Melanie, Khurana Hershey, Gurjit K, O'Connor, George T, Pongracic, Jacqueline A, Sherenian, Michael G, Rivera-Spoljaric, Katherine, Zoratti, Edward M, Teach, Stephen J, Kattan, Meyer, Dutmer, Cullen M, Kim, Haejin, Lamm, Carin, Sheehan, William J, Segnitz, R Max, Dill-McFarland, Kimberly A, Visness, Cynthia M, Becker, Patrice M, Gern, James E, Sorkness, Christine A, Busse, William W, and Altman, Matthew C

Published
2022
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16. African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

Author

Washington, III, Charles, Dapas, Matthew, Biddanda, Arjun, Magnaye, Kevin M., Aneas, Ivy, Helling, Britney A., Szczesny, Brooke, Boorgula, Meher Preethi, Taub, Margaret A., Kenny, Eimear, Mathias, Rasika A., Barnes, Kathleen C., Khurana Hershey, Gurjit K., Kercsmar, Carolyn M., Gereige, Jessica D., Makhija, Melanie, Gruchalla, Rebecca S., Gill, Michelle A., Liu, Andrew H., Rastogi, Deepa, Busse, William, Gergen, Peter J., Visness, Cynthia M., Gold, Diane R., Hartert, Tina, Johnson, Christine C., Lemanske, Jr., Robert F., Martinez, Fernando D., Miller, Rachel L., Ownby, Dennis, Seroogy, Christine M., Wright, Anne L., Zoratti, Edward M., Bacharier, Leonard B., Kattan, Meyer, O’Connor, George T., Wood, Robert A., Nobrega, Marcelo A., Altman, Matthew C., Jackson, Daniel J., Gern, James E., McKennan, Christopher G., and Ober, Carole

Published
2022
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17. Emergency management and asthma risk in young Medicaid-enrolled children with recurrent wheeze.

Author

Hardee, Isabel J., Zaniletti, Isabella, Tanverdi, Melisa S., Liu, Andrew H., Mistry, Rakesh D., and Navanandan, Nidhya

Subjects
EMERGENCY room visits, ASTHMA in children, RACE, EMERGENCY management, LOGISTIC regression analysis, WHEEZE
Abstract

Objectives: To describe clinical characteristics of young children presenting to the emergency department (ED) for early recurrent wheeze, and determine factors associated with subsequent persistent wheeze and risk for early childhood asthma. Methods: Retrospective cohort study of Medicaid-enrolled children 0–3 years old with an index ED visit for wheeze (e.g. bronchiolitis, reactive airway disease) from 2009 to 2013, and at least one prior documented episode of wheeze at an ED or primary care visit. The primary outcome was persistent wheeze between 4 and 6 years of age. Demographics and clinical characteristics were collected from the index ED visit. Logistic regression was used to estimate the association between potential risk factors and subsequent persistent wheeze. Results: During the study period, 41,710 children presented to the ED for recurrent wheeze. Mean age was 1.3 years; 59% were male, 42% Black, and 6% Hispanic. At index ED visits, the most common diagnosis was acute bronchiolitis (40%); 77% of children received an oral corticosteroid prescription. Between 4 and 6 years of age, 11,708 (28%) children had persistent wheeze. A greater number of wheezing episodes was associated with an increased odds of ED treatment with asthma medications. Subsequent persistent wheeze was associated with male sex, Black race, atopy, prescription for bronchodilators or corticosteroids, and greater number of visits for wheeze. Conclusions: Young children with persistent wheeze are at risk for childhood asthma. Thus, identification of risk factors associated with persistent wheeze in young children with recurrent wheeze might aid in early detection of asthma and initiation of preventative therapies. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium

Author

Felix, Janine F, Joubert, Bonnie R, Baccarelli, Andrea A, Sharp, Gemma C, Almqvist, Catarina, Annesi-Maesano, Isabella, Arshad, Hasan, Baïz, Nour, Bakermans-Kranenburg, Marian J, Bakulski, Kelly M, Binder, Elisabeth B, Bouchard, Luigi, Breton, Carrie V, Brunekreef, Bert, Brunst, Kelly J, Burchard, Esteban G, Bustamante, Mariona, Chatzi, Leda, Munthe-Kaas, Monica Cheng, Corpeleijn, Eva, Czamara, Darina, Dabelea, Dana, Smith, George Davey, De Boever, Patrick, Duijts, Liesbeth, Dwyer, Terence, Eng, Celeste, Eskenazi, Brenda, Everson, Todd M, Falahi, Fahimeh, Fallin, M Daniele, Farchi, Sara, Fernandez, Mariana F, Gao, Lu, Gaunt, Tom R, Ghantous, Akram, Gillman, Matthew W, Gonseth, Semira, Grote, Veit, Gruzieva, Olena, Håberg, Siri E, Herceg, Zdenko, Hivert, Marie-France, Holland, Nina, Holloway, John W, Hoyo, Cathrine, Hu, Donglei, Huang, Rae-Chi, Huen, Karen, Järvelin, Marjo-Riitta, Jima, Dereje D, Just, Allan C, Karagas, Margaret R, Karlsson, Robert, Karmaus, Wilfried, Kechris, Katerina J, Kere, Juha, Kogevinas, Manolis, Koletzko, Berthold, Koppelman, Gerard H, Küpers, Leanne K, Ladd-Acosta, Christine, Lahti, Jari, Lambrechts, Nathalie, Langie, Sabine AS, Lie, Rolv T, Liu, Andrew H, Magnus, Maria C, Magnus, Per, Maguire, Rachel L, Marsit, Carmen J, McArdle, Wendy, Melén, Erik, Melton, Phillip, Murphy, Susan K, Nawrot, Tim S, Nisticò, Lorenza, Nohr, Ellen A, Nordlund, Björn, Nystad, Wenche, Oh, Sam S, Oken, Emily, Page, Christian M, Perron, Patrice, Pershagen, Göran, Pizzi, Costanza, Plusquin, Michelle, Raikkonen, Katri, Reese, Sarah E, Reischl, Eva, Richiardi, Lorenzo, Ring, Susan, Roy, Ritu P, Rzehak, Peter, Schoeters, Greet, Schwartz, David A, Sebert, Sylvain, Snieder, Harold, Sørensen, Thorkild IA, and Starling, Anne P

Subjects
Epidemiology, Public Health, Health Sciences, Statistics, Mathematical Sciences, Child Health, Cohort Studies, DNA Methylation, Environmental Pollution, Epigenesis, Genetic, Female, Folic Acid, Humans, Infant, Newborn, Maternal Exposure, Maternal Health, Pregnancy, Prenatal Exposure Delayed Effects, Public Health and Health Services, Public health
Published
2018

19. Dual RNA-seq reveals viral infections in asthmatic children without respiratory illness which are associated with changes in the airway transcriptome

Author

Wesolowska-Andersen, Agata, Everman, Jamie L, Davidson, Rebecca, Rios, Cydney, Herrin, Rachelle, Eng, Celeste, Janssen, William J, Liu, Andrew H, Oh, Sam S, Kumar, Rajesh, Fingerlin, Tasha E, Rodriguez-Santana, Jose, Burchard, Esteban G, and Seibold, Max A

Subjects
Medical Microbiology, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Biological Sciences, Infectious Diseases, Vaccine Related, Prevention, Emerging Infectious Diseases, Pediatric, Biotechnology, Lung, Genetics, Biodefense, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Infection, Inflammatory and immune system, Good Health and Well Being, Asthma, Case-Control Studies, Child, Gene Expression Profiling, Gene Expression Regulation, Viral, High-Throughput Nucleotide Sequencing, Host-Pathogen Interactions, Humans, RNA Virus Infections, RNA Viruses, Respiratory Mucosa, Respiratory Tract Infections, Sequence Analysis, RNA, Transcriptome, Asymptomatic, Virus, Airway epithelium, RNA-seq, Children, Host response, Host-virus interactions, Environmental Sciences, Information and Computing Sciences, Bioinformatics
Abstract

BackgroundRespiratory illness caused by viral infection is associated with the development and exacerbation of childhood asthma. Little is known about the effects of respiratory viral infections in the absence of illness. Using quantitative PCR (qPCR) for common respiratory viruses and for two genes known to be highly upregulated in viral infections (CCL8/CXCL11), we screened 92 asthmatic and 69 healthy children without illness for respiratory virus infections.ResultsWe found 21 viral qPCR-positive and 2 suspected virus-infected subjects with high expression of CCL8/CXCL11. We applied a dual RNA-seq workflow to these subjects, together with 25 viral qPCR-negative subjects, to compare qPCR with sequencing-based virus detection and to generate the airway transcriptome for analysis. RNA-seq virus detection achieved 86% sensitivity when compared to qPCR-based screening. We detected additional respiratory viruses in the two CCL8/CXCL11-high subjects and in two of the qPCR-negative subjects. Viral read counts varied widely and were used to stratify subjects into Virus-High and Virus-Low groups. Examination of the host airway transcriptome found that the Virus-High group was characterized by immune cell airway infiltration, downregulation of cilia genes, and dampening of type 2 inflammation. Even the Virus-Low group was differentiated from the No-Virus group by 100 genes, some involved in eIF2 signaling.ConclusionsRespiratory virus infection without illness is not innocuous but may determine the airway function of these subjects by driving immune cell airway infiltration, cellular remodeling, and alteration of asthmogenic gene expression.

Published
2017

20. Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods

Author

Fulkerson, Patricia C, primary, Lussier, Stephanie J, additional, Bendixsen, Casper G, additional, Castina, Sharon M, additional, Gebretsadik, Tebeb, additional, Marlin, Jessica S, additional, Russell, Patty B, additional, Seibold, Max A, additional, Everman, Jamie L, additional, Moore, Camille M, additional, Snyder, Brittney M, additional, Thompson, Kathy, additional, Tregoning, George S, additional, Wellford, Stephanie, additional, Arbes, Samuel J, additional, Bacharier, Leonard B, additional, Calatroni, Agustin, additional, Camargo Jr, Carlos A, additional, Dupont, William D, additional, Furuta, Glenn T, additional, Gruchalla, Rebecca S, additional, Gupta, Ruchi S, additional, Hershey, Gurjit Khurana, additional, Jackson, Daniel J, additional, Johnson, Christine C, additional, Kattan, Meyer, additional, Liu, Andrew H, additional, Murrison, Liza, additional, O’Connor, George T, additional, Phipatanakul, Wanda, additional, Rivera-Spoljaric, Katherine, additional, Rothenberg, Marc E, additional, Seroogy, Christine M, additional, Teach, Stephen J, additional, Zoratti, Edward M, additional, Togias, Alkis, additional, Hartert, Tina V, additional, and HEROS study team, on behalf of the, additional

Published
2024
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21. Childhood asthma exacerbations on the Navajo Nation

Author

Bender, Bruce G., primary, Crooks, James, additional, Gerald, Joe K., additional, Hudson, Bryan, additional, King, Diane K., additional, Kobernick, Aaron, additional, Liu, Andrew H., additional, Lowe, Ashley A., additional, Morgan, Wayne, additional, Nez, Peter, additional, Phan, Hanna, additional, Wightman, Patrick, additional, and Gerald, Lynn B., additional

Published
2024
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29. Epigenome-wide meta-analysis of DNA methylation and childhood asthma

Author

Reese, Sarah E., Xu, Cheng-Jian, den Dekker, Herman T., Lee, Mi Kyeong, Sikdar, Sinjini, Ruiz-Arenas, Carlos, Merid, Simon K., Rezwan, Faisal I., Page, Christian M., Ullemar, Vilhelmina, Melton, Phillip E., Oh, Sam S., Yang, Ivana V., Burrows, Kimberley, Söderhäll, Cilla, Jima, Dereje D., Gao, Lu, Arathimos, Ryan, Küpers, Leanne K., Wielscher, Matthias, Rzehak, Peter, Lahti, Jari, Laprise, Catherine, Madore, Anne-Marie, Ward, James, Bennett, Brian D., Wang, Tianyuan, Bell, Douglas A., Vonk, Judith M., Håberg, Siri E., Zhao, Shanshan, Karlsson, Robert, Hollams, Elysia, Hu, Donglei, Richards, Adam J., Bergström, Anna, Sharp, Gemma C., Felix, Janine F., Bustamante, Mariona, Gruzieva, Olena, Maguire, Rachel L., Gilliland, Frank, Baïz, Nour, Nohr, Ellen A., Corpeleijn, Eva, Sebert, Sylvain, Karmaus, Wilfried, Grote, Veit, Kajantie, Eero, Magnus, Maria C., Örtqvist, Anne K., Eng, Celeste, Liu, Andrew H., Kull, Inger, Jaddoe, Vincent W.V., Sunyer, Jordi, Kere, Juha, Hoyo, Cathrine, Annesi-Maesano, Isabella, Arshad, Syed Hasan, Koletzko, Berthold, Brunekreef, Bert, Binder, Elisabeth B., Räikkönen, Katri, Reischl, Eva, Holloway, John W., Jarvelin, Marjo-Riitta, Snieder, Harold, Kazmi, Nabila, Breton, Carrie V., Murphy, Susan K., Pershagen, Göran, Anto, Josep Maria, Relton, Caroline L., Schwartz, David A., Burchard, Esteban G., Huang, Rae-Chi, Nystad, Wenche, Almqvist, Catarina, Henderson, A. John, Melén, Erik, Duijts, Liesbeth, Koppelman, Gerard H., and London, Stephanie J.

Published
2019
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31. Rhinitis in children and adolescents with asthma: Ubiquitous, difficult to control, and associated with asthma outcomes

Author

Togias, Alkis, Gergen, Peter J., Hu, Jack W., Babineau, Denise C., Wood, Robert A., Cohen, Robyn T., Makhija, Melanie M., Khurana Hershey, Gurjit K., Kercsmar, Carolyn M., Gruchalla, Rebecca S., Liu, Andrew H., Wang, Emily, Kim, Haejin, Lamm, Carin I., Bacharier, Leonard B., Pillai, Dinesh, Sigelman, Steve M., Gern, James E., and Busse, William W.

Published
2019
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34. Dissecting childhood asthma with nasal transcriptomics distinguishes subphenotypes of disease

Author

Poole, Alex, Urbanek, Cydney, Eng, Celeste, Schageman, Jeoffrey, Jacobson, Sean, O'Connor, Brian P, Galanter, Joshua M, Gignoux, Christopher R, Roth, Lindsey A, Kumar, Rajesh, Lutz, Sharon, Liu, Andrew H, Fingerlin, Tasha E, Setterquist, Robert A, Burchard, Esteban G, Rodriguez-Santana, Jose, and Seibold, Max A

Subjects
Biomedical and Clinical Sciences, Immunology, Genetics, Asthma, Lung, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Adolescent, Bronchi, Female, Gene Expression Profiling, Genome-Wide Association Study, Humans, Interleukin-13, Male, Nasal Mucosa, Phenotype, Th2 Cells, Nasal airway epithelium, transcriptome, T(H)2, asthma, bronchial airway epithelium, Allergy
Abstract

BackgroundBronchial airway expression profiling has identified inflammatory subphenotypes of asthma, but the invasiveness of this technique has limited its application to childhood asthma.ObjectivesWe sought to determine whether the nasal transcriptome can proxy expression changes in the lung airway transcriptome in asthmatic patients. We also sought to determine whether the nasal transcriptome can distinguish subphenotypes of asthma.MethodsWhole-transcriptome RNA sequencing was performed on nasal airway brushings from 10 control subjects and 10 asthmatic subjects, which were compared with established bronchial and small-airway transcriptomes. Targeted RNA sequencing nasal expression analysis was used to profile 105 genes in 50 asthmatic subjects and 50 control subjects for differential expression and clustering analyses.ResultsWe found 90.2% overlap in expressed genes and strong correlation in gene expression (ρ = .87) between the nasal and bronchial transcriptomes. Previously observed asthmatic bronchial differential expression was strongly correlated with asthmatic nasal differential expression (ρ = 0.77, P = 5.6 × 10(-9)). Clustering analysis identified TH2-high and TH2-low subjects differentiated by expression of 70 genes, including IL13, IL5, periostin (POSTN), calcium-activated chloride channel regulator 1 (CLCA1), and serpin peptidase inhibitor, clade B (SERPINB2). TH2-high subjects were more likely to have atopy (odds ratio, 10.3; P = 3.5 × 10(-6)), atopic asthma (odds ratio, 32.6; P = 6.9 × 10(-7)), high blood eosinophil counts (odds ratio, 9.1; P = 2.6 × 10(-6)), and rhinitis (odds ratio, 8.3; P = 4.1 × 10(-6)) compared with TH2-low subjects. Nasal IL13 expression levels were 3.9-fold higher in asthmatic participants who experienced an asthma exacerbation in the past year (P = .01). Several differentially expressed nasal genes were specific to asthma and independent of atopic status.ConclusionNasal airway gene expression profiles largely recapitulate expression profiles in the lung airways. Nasal expression profiling can be used to identify subjects with IL13-driven asthma and a TH2-skewed systemic immune response.

Published
2014

35. Gene-based association study of rare variants in children of diverse ancestries implicates TNFRSF21 in the development of allergic asthma

Author

Clay, Selene, primary, Alladina, Jehan, additional, Smith, Neal P., additional, Visness, Cynthia M., additional, Wood, Robert A., additional, O’Connor, George T., additional, Cohen, Robyn T., additional, Khurana Hershey, Gurjit K., additional, Kercsmar, Carolyn M., additional, Gruchalla, Rebecca S., additional, Gill, Michelle A., additional, Liu, Andrew H., additional, Kim, Haejin, additional, Kattan, Meyer, additional, Bacharier, Leonard B., additional, Rastogi, Deepa, additional, Rivera-Spoljaric, Katherine, additional, Robison, Rachel G., additional, Gergen, Peter J., additional, Busse, William W., additional, Villani, Alexandra-Chloe, additional, Cho, Josalyn L., additional, Medoff, Benjamin D., additional, Gern, James E., additional, Jackson, Daniel J., additional, Ober, Carole C., additional, and Dapas, Matthew, additional

Published
2023
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39. Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children

Author

Altman, Matthew C., Gill, Michelle A., Whalen, Elizabeth, Babineau, Denise C., Shao, Baomei, Liu, Andrew H., Jepson, Brett, Gruchalla, Rebecca S., O’Connor, George T., Pongracic, Jacqueline A., Kercsmar, Carolyn M., Khurana Hershey, Gurjit K., Zoratti, Edward M., Johnson, Christine C., Teach, Stephen J., Kattan, Meyer, Bacharier, Leonard B., Beigelman, Avraham, Sigelman, Steve M., Presnell, Scott, Gern, James E., Gergen, Peter J., Wheatley, Lisa M., Togias, Alkis, Busse, William W., and Jackson, Daniel J.

Published
2019
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43. Distinguishing characteristics of difficult-to-control asthma in inner-city children and adolescents

Author

Pongracic, Jacqueline A., Krouse, Rebecca Z., Babineau, Denise C., Zoratti, Edward M., Cohen, Robyn T., Wood, Robert A., Khurana Hershey, Gurjit K., Kercsmar, Carolyn M., Gruchalla, Rebecca S., Kattan, Meyer, Teach, Stephen J., Johnson, Christine C., Bacharier, Leonard B., Gern, James E., Sigelman, Steven M., Gergen, Peter J., Togias, Alkis, Visness, Cynthia M., Busse, William W., and Liu, Andrew H.

Published
2016
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44. Pathways through which asthma risk factors contribute to asthma severity in inner-city children

Author

Liu, Andrew H., Babineau, Denise C., Krouse, Rebecca Z., Zoratti, Edward M., Pongracic, Jacqueline A., O'Connor, George T., Wood, Robert A., Khurana Hershey, Gurjit K., Kercsmar, Carolyn M., Gruchalla, Rebecca S., Kattan, Meyer, Teach, Stephen J., Makhija, Melanie, Pillai, Dinesh, Lamm, Carin I., Gern, James E., Sigelman, Steven M., Gergen, Peter J., Togias, Alkis, Visness, Cynthia M., and Busse, William W.

Published
2016
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45. Asthma phenotypes in inner-city children

Author

Zoratti, Edward M., Krouse, Rebecca Z., Babineau, Denise C., Pongracic, Jacqueline A., O'Connor, George T., Wood, Robert A., Khurana Hershey, Gurjit K., Kercsmar, Carolyn M., Gruchalla, Rebecca S., Kattan, Meyer, Teach, Stephen J., Sigelman, Steven M., Gergen, Peter J., Togias, Alkis, Visness, Cynthia M., Busse, William W., and Liu, Andrew H.

Published
2016
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48. Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations

Author

Teach, Stephen J., Gill, Michelle A., Togias, Alkis, Sorkness, Christine A., Arbes, Samuel J., Jr., Calatroni, Agustin, Wildfire, Jeremy J., Gergen, Peter J., Cohen, Robyn T., Pongracic, Jacqueline A., Kercsmar, Carolyn M., Khurana Hershey, Gurjit K., Gruchalla, Rebecca S., Liu, Andrew H., Zoratti, Edward M., Kattan, Meyer, Grindle, Kristine A., Gern, James E., Busse, William W., and Szefler, Stanley J.

Published
2015
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49. List of Contributors

Author

Bacharier, Leonard B., primary, Barberis, Nicole, additional, Burckart, Gilbert J., additional, Busse, William W., additional, Carr, Tara F., additional, Castro, Mario, additional, Chung, Kian Fan, additional, Cicutto, Lisa, additional, Elie, Marc, additional, Fitzpatrick, Anne M., additional, Federico, Monica J., additional, Gaefke, Claudia L., additional, Green, Dionna, additional, Haahtela, Tari, additional, Hall, Chase, additional, Hoch, Heather, additional, Holguin, Fernando, additional, Huang, Yvonne J., additional, Johnston, Katherine, additional, Katial, Rohit K., additional, Liu, Andrew H., additional, Malka, Jonathan, additional, Nkrumah-Elie, Yasmeen, additional, Ortega, Victor E., additional, Pennington, Emily J., additional, Permaul, Perdita, additional, Phipatanakul, Wanda, additional, Reisdorph, Nichole, additional, Sears, Malcolm R., additional, Sood, Shweta, additional, Selroos, Olof, additional, Spahn, Joseph D., additional, Stokes, Jeffrey R., additional, Subbarao, Padmaja, additional, Szefler, Stanley J., additional, Wang, Eileen, additional, and Wechsler, Michael E., additional

Published
2018
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