93 results on '"M. CASTRO"'
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2. Evolutive Profile Of Iga Deficiency Patients From A Pediatric Brazilian Reference Center For Primary Immunodeficiency
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Antonio Carlos Pastorino, A.B.F. Fomin, A. P. M. Castro, L.A. Watanabe, M. T. Iwashita, Mayra de Barros Dorna, M.D. Asanuma, D.G.C. Rezende, Magda Carneiro-Sampaio, and C.M.A. Jacob
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Pediatrics ,medicine.medical_specialty ,business.industry ,Immunology ,medicine ,Primary immunodeficiency ,Immunology and Allergy ,IgA deficiency ,Center (algebra and category theory) ,business ,medicine.disease - Published
- 2010
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Catalog
3. X-linked Disorder Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked (ipex) In Brazilian Twins Brothers - A Report
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J. Tanno, V.H. Koch, Vanessa Cristina de Oliveira, M.M.S. Carneiro Sampaio, C.M.A. Jacob, Jady Rodrigues De Oliveira, A.B.F. Fomin, T. Dela Mana, Antonio Carlos Pastorino, and A. P. M. Castro
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business.industry ,Immunology ,medicine ,Immunology and Allergy ,Enteropathy ,Immune dysregulation ,medicine.disease_cause ,business ,medicine.disease - Published
- 2009
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4. Follow Up Of Hepatic Abscess In Chronic Granulomatous Disease (cgd): Clinical Experience Of A Brazilian Reference Center In Primary Imunodeficiecy (pid)
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L.A. Watanabe, C.M.A. Jacob, C.M. Lui, L.A. Soubihe, F.R. Kibrit, Antonio Carlos Pastorino, A. P. M. Castro, A.B.F. Fomin, and D.G.C. Rezende
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medicine.medical_specialty ,Chronic granulomatous disease ,business.industry ,Immunology ,Hepatic abscess ,Immunology and Allergy ,Medicine ,business ,medicine.disease ,Surgery - Published
- 2009
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5. Could Cow's Milk Fractions Contribute toImprove Diagnosis of IgE Mediated Cow's Milk Allergy?
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C.M.A. Jacob, C.M. Lui, A.K.F. Gushken, R. Melo, A.B.F. Fomin, M. Higa, Antonio Carlos Pastorino, A. P. M. Castro, and Letícia Aki Watanabe
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Ige mediated ,Cow's milk allergy ,business.industry ,Immunology ,Immunology and Allergy ,Medicine ,business - Published
- 2008
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6. Serological Determination of Cytokines in Chromomycosis
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M. Castro, H. Drikha, D.C. Rodriguez, I. Castro, E. Martinez, and B. Camacho
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Immunology ,Immunology and Allergy ,Serology - Published
- 2008
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7. Is it Possible to Establish a Clinical and Laboratorial Profile in Persistent Cow's Milk Allergic Patients?
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A.C. Brandão, A.K.F. Gushken, A. P. M. Castro, F.R. Kibrit, L.A. Soubihe, C.M.A. Jacob, A.B.F. Fomin, and Antonio Carlos Pastorino
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Immunology ,Immunology and Allergy - Published
- 2008
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8. IgE Mediated Cow's Milk Allergy (CMA): Evaluation of Weight and Height of Patients at Admission and After one-year Follow-up in Use of Soy Products
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A. P. M. Castro, Glauce Hiromi Yonamine, F.R.P. Afonso, Antonio Carlos Pastorino, Gabriela Ackel Corradi, and C.M.A. Jacob
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Pediatrics ,medicine.medical_specialty ,Ige mediated ,One year follow up ,Cow's milk allergy ,business.industry ,Immunology ,medicine ,Immunology and Allergy ,business - Published
- 2007
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9. Egg's allergy: an experience from Brazilian Food Allergy Reference Center
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R.G. Ramos, D. Munhoz, A.C. Brandão, T. Batelochio, C.M.A. Jacob, A. P. M. Castro, Antonio Carlos Pastorino, Glauce Hiromi Yonamine, and A.K.F. Gushken
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medicine.medical_specialty ,Allergy ,business.industry ,Food allergy ,Family medicine ,Immunology ,Immunology and Allergy ,Medicine ,Center (algebra and category theory) ,business ,medicine.disease - Published
- 2007
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10. Clinical And Laboratorial Findings From Ige Mediated Cow's Milk Allergy (CMA) In Brazilian Pediatric Patients
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A.K.F. Gushken, A. P. M. Castro, C.M.A. Jacob, Glauce Hiromi Yonamine, A.C. Brandão, D.L.A. Pitarello, E. Ciccone, and Antonio Carlos Pastorino
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Ige mediated ,Cow's milk allergy ,business.industry ,Immunology ,Immunology and Allergy ,Medicine ,business - Published
- 2007
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11. Concordance Rates of Allergen Sensitization Amongst Family Members at an Inner City Asthma Center
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M. Rao, Corinna S. Bowser, F. Hajee, M. Castro, Rauno Joks, and H. Solomon
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Inner city asthma ,Allergic sensitization ,medicine.medical_specialty ,business.industry ,Family medicine ,Concordance ,Immunology ,medicine ,Immunology and Allergy ,Center (algebra and category theory) ,business - Published
- 2007
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12. What Specific IgE Levels to Milk Protein Fractions May Contribute to Cow's Milk (CM) Allergy Diagnosis?
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C.M.A. Jacob, A.K.F. Gushken, A. P. M. Castro, Antonio Carlos Pastorino, E. Ciccone, and A.C. Brandão
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Allergy ,Milk protein ,Immunology ,medicine ,biology.protein ,Immunology and Allergy ,Biology ,medicine.disease ,Immunoglobulin E - Published
- 2006
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13. Lung Involvement During Follow-Up of 12 patients with Agammaglobulinemia
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Mayra de Barros Dorna, A.B.F. Fomin, C.M.A. Jacob, Antonio Carlos Pastorino, A. P. M. Castro, E.M.G. Carnide, and E.G. Marins
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medicine.medical_specialty ,business.industry ,Internal medicine ,Immunology ,Immunology and Allergy ,Medicine ,business ,Gastroenterology ,Lung involvement - Published
- 2006
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14. Establishing a Milk Specific IgE Decision Point in IgE Mediated Cow'S Milk Allergy (CMA) Patients from a Tertiary Pediatric Brazilian Center
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A. P. M. Castro, R.F.F. Gonçalves, A.K.F. Gushken, E. Ciccone, C.M.A. Jacob, and Antonio Carlos Pastorino
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Decision points ,Milk specific IgE ,Ige mediated ,business.industry ,Cow's milk allergy ,Immunology ,Immunology and Allergy ,Medicine ,business - Published
- 2006
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15. Common variable immunodeficiency (CVID) and cryptosporidiosis of difficult control
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A.M. Lima, C.M.A. Jacob, A. P. M. Castro, E. Ciccone, Luiz Vicente Rizzo, Antonio Carlos Pastorino, Gabriela Ackel Corradi, and E.M.G. Carnide
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business.industry ,Common variable immunodeficiency ,Immunology ,medicine ,Immunology and Allergy ,medicine.disease ,business - Published
- 2005
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16. Inverse relationship of plasma C5a levels to allergic disease activity in pediatric but not adult populations
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C. Charlot, Rauno Joks, F. Hajee, H. Drew, M. Nowakowski, M. Castro, O. Asimolowo, Corinna S. Bowser, Seto Chice, M. Rao, and N. Mathur
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Disease activity ,Pathology ,medicine.medical_specialty ,business.industry ,Immunology ,Immunology and Allergy ,Medicine ,business - Published
- 2005
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17. Transient hypogammaglobulinemia in a child with multiple infections and dysmorphic features*1
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M. Castro, N. Mathur, R. Wallerstein, and Hamid Moallem
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Pediatrics ,medicine.medical_specialty ,Respiratory tract infections ,business.industry ,Immunology ,medicine.disease ,Asymptomatic ,Transient Hypogammaglobulinemia ,medicine ,Etiology ,Immunology and Allergy ,medicine.symptom ,Transient hypogammaglobulinemia of infancy ,business ,Hemophilus ,Meningitis ,Full Term - Abstract
Transient Hypogammaglobulinemia of Infancy (THI) is an uncommon disease entity in which the exact incidence, definition, etiology and outcome remain to be unknown. Affected individuals may be asymptomatic or may have increased frequency of infections. We are reporting a 5 year old boy with dysmorphic features, double left ureter, supravalvular stenosis, laryngotracheobronchomalacia, seizure disorder and multiple serious bacterial infections. The patient had Pneumococcal meningitis at age 7 months and two episodes of Klebsiella sepsis at age 7 weeks and 8 months. He was born full term via spontaneous vaginal delivery with ABO incompatibility for which he received exchange transfusion. Family history is unremarkable. Significant findings in the physical examination included large anterior fontanelle, hypertelorism, downslanted palpebral fissures, bilateral pre-auricular sinuses and wide-shaped, pointed teeth. Laboratory evaluation showed low serum immunoglobulins. Antibodies to tetanus and diptheria toxoids and hemophilus influenza b were present. Lymphocyte subsets, as well as, lymphocyte proliferative response to PHA , con-A and pokeweed mitogens were within normal limits for age. Serum complement levels and nitroblue tetrazolium test (NBT) were also normal. Delayed type hypersensitivity testing with PPD , candida and tetanus remained negative. Cytogenetic studies failed to detect any chromosomal abnormality. HIV testing was negative. The patient was followed closely in Immunology clinic. He did not develop any subsequent problems except for mild upper respiratory tract infections which were managed symptomatically. At 5 years of age, the patient's panhypogammaglobulinemia resolved. more...
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- 2004
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18. Wegener's granulomatosis in a 16-year-old girl*1
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Hamid Moallem, M. Castro, C. Bowser, and N. Mathur
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medicine.medical_specialty ,Proteinuria ,Erythema ,Urinalysis ,medicine.diagnostic_test ,business.industry ,Immunology ,Episcleritis ,medicine.disease ,Gastroenterology ,Surgery ,Paranasal sinuses ,medicine.anatomical_structure ,Cellulitis ,Internal medicine ,Edema ,medicine ,Immunology and Allergy ,medicine.symptom ,business ,Respiratory tract - Abstract
A 16-year-old African-American girl presented to our institution with a 6-week history of swollen ankles and 5-week history of conjunctival injection. She had previously been treated with antibiotics for suspected lower extremity cellulitis. Bilateral ankle swelling with erythema and episcleritis were remarkable clinical findings. Laboratory investigations showed: normal CBC and differential, ESR 68 mm/hr, serum BUN 15 mg/dL, and serum creatinine 1.0 mg/dL. Urinalysis showed proteinuria and hematuria although 24-hour urine collection was normal for protein. Antinuclear antibody (ANA) and anti-proteinase-3 antibodies (C-ANCA) were detected while anti-myeloperoxidase antibody (P-ANCA) was absent. CT scan of the chest showed multiple granulomas in both lungs. MRI of the paranasal sinuses, orbits and brain were unremarkable. With a diagnosis of Wegener's granulomatosis (WG), she was started on intravenous solumedrol and cyclophosphamide and maintained on daily oral doses of both medications. Two weeks after initiation of therapy, she was admitted with acute renal failure and massive edema of the labia majora and pitting edema of lower extremities. WG is a granulomatous vasculitis affecting the respiratory tract and kidneys. It occurs mostly between the ages of 20 and 40 years and appears to affect men and women equally. While glomerulonephritis is seen in about 25% of patients at the time of diagnosis, mucosal inflammation of the respiratory tract is reported in as many as 75% of cases. The patient presented here is an unusual case of WG occurring in adolescence with involvement of the lower respiratory tract and rapid progression to acute renal failure. more...
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- 2004
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19. Latex allergy
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A.S. Josephson, Hamid Moallem, Rauno Joks, M. Castro, and N. Mathur
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History ,Immunology ,Immunology and Allergy ,Library science - Published
- 2003
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20. Hypogammaglobulinemia associated with herpes zoster virus infection
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P. V. Zaia, A. P. M. Castro, C.M.A. Jacob, A.B.F. Fomin, and Antonio Carlos Pastorino
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Hypogammaglobulinemia ,business.industry ,Immunology ,medicine ,Immunology and Allergy ,Herpes zoster virus ,medicine.disease ,business ,Virology - Published
- 2003
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21. 778 St. Louis asthma database
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L.K. Sussman, J.W. Knutson, Raymond G. Slavin, and M. Castro
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medicine.medical_specialty ,business.industry ,Family medicine ,Immunology ,medicine ,Immunology and Allergy ,medicine.disease ,business ,Asthma ,St louis - Published
- 1996
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22. Mitochondrial DNA copy number variation in asthma risk, severity, and exacerbations.
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Xu W, Hong YS, Hu B, Comhair SAA, Janocha AJ, Zein JG, Chen R, Meyers DA, Mauger DT, Ortega VE, Bleecker ER, Castro M, Denlinger LC, Fahy JV, Israel E, Levy BD, Jarjour NN, Moore WC, Wenzel SE, Gaston B, Liu C, Arking DE, and Erzurum SC more...
- Abstract
Background: Asthma pathophysiology is associated with mitochondrial dysfunction. Mitochondrial DNA copy number (mtDNA-CN) has been used as a proxy of mitochondrial function, with lower levels indicating mitochondrial dysfunction in population studies of cardiovascular diseases and cancers., Objectives: We investigated whether lower levels of mtDNA-CN are associated with asthma diagnosis, severity, and exacerbations., Methods: mtDNA-CN is evaluated in blood from 2 cohorts: UK Biobank (UKB) (asthma, n = 39,147; no asthma, n = 302,302) and Severe Asthma Research Program (SARP) (asthma, n = 1283; nonsevere asthma, n = 703)., Results: Individuals with asthma have lower mtDNA-CN compared to individuals without asthma in UKB (beta, -0.006 [95% confidence interval, -0.008 to -0.003], P = 6.23 × 10
-6 ). Lower mtDNA-CN is associated with asthma prevalence, but not severity in UKB or SARP. mtDNA-CN declines with age but is lower in individuals with asthma than in individuals without asthma at all ages. In a 1-year longitudinal study in SARP, mtDNA-CN was associated with risk of exacerbation; those with highest mtDNA-CN had the lowest risk of exacerbation (odds ratio 0.333 [95% confidence interval, 0.173 to 0.542], P = .001). Biomarkers of inflammation and oxidative stress are higher in individuals with asthma than without asthma, but the lower mtDNA-CN in asthma is independent of general inflammation or oxidative stress. Mendelian randomization studies suggest a potential causal relationship between asthma-associated genetic variants and mtDNA-CN., Conclusion: mtDNA-CN is lower in asthma than in no asthma and is associated with exacerbations. Low mtDNA-CN in asthma is not mediated through inflammation but is associated with a genetic predisposition to asthma., Competing Interests: Disclosure statement This research was conducted using the UK Biobank Resource under application 17731. The study was supported by the National Heart, Lung, and Blood Institute (NHLBI; HL081064, HL103453, and HL144569) and the National Center for Advancing Translational Sciences (ULTR000439). The Severe Asthma Research Program (SARP) was supported by awards from the National Heart, Lung, and Blood Institute (U10 HL109172, U10 HL109168, U10 HL109152, U10 HL109257, U10 HL109046, U10 HL109250, U10 HL109164, and U10 HL109086). SARP mitochondrial DNA copy numbers were from the Trans-omics in Precision Medicine (TOPMed) program supported by the NHLBI. Core support including centralized genomic read mapping and genotype calling, along with variant quality metrics and filtering, was provided by the TOPMed Informatics Research Center (3R01HL117626-02S1; contract HHSN268201800002I). Core support including phenotype harmonization, data management, sample-identity quality control, and general program coordination was provided by the TOPMed Data Coordinating Center (R01HL120393; U01HL120393; contract HHSN268201800001I). Industry support was provided for SARP III from AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Sanofi-Genzyme-Regeneron, and Teva. The following companies provided financial support for study activities at the Coordinating and Clinical Centers beyond the third year of patient follow-up: AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Sanofi-Genzyme-Regeneron, and Teva. These companies had no role in study design or data analysis, and the only restriction on the funds was that they be used to support the SARP initiative. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.) more...- Published
- 2024
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23. Utility of eosinophil peroxidase as a biomarker of eosinophilic inflammation in asthma.
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Tang M, Charbit AR, Johansson MW, Jarjour NN, Denlinger LC, Raymond WW, Peters MC, Dunican EM, Castro M, Sumino K, Erzurum SC, Comhair SA, Moore WC, Levy BD, Israel E, Phipatanakul W, Phillips BR, Mauger DT, Bleecker ER, Wenzel SE, Fajt ML, Woodruff PG, Hastie AT, and Fahy JV more...
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- Humans, Male, Female, Middle Aged, Adult, Leukocyte Count, Inflammation, Aged, Antibodies, Monoclonal, Humanized, Asthma blood, Asthma diagnosis, Asthma immunology, Asthma drug therapy, Eosinophil Peroxidase metabolism, Biomarkers blood, Sputum immunology, Eosinophils immunology
- Abstract
Background: The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain., Objective: We sought to determine the utility of EPX as a biomarker of systemic and airway eosinophilic inflammation in asthma., Methods: EPX protein was measured by immunoassay in serum and sputum in 110 healthy controls to establish a normal reference range and in repeated samples of serum and sputum collected during 3 years of observation in 480 participants in the Severe Asthma Research Program 3., Results: Over 3 years, EPX levels in patients with asthma were higher than normal in 27% to 31% of serum samples and 36% to 53% of sputum samples. Eosinophils and EPX correlated better in blood than in sputum (r
s values of 0.74 and 0.43, respectively), and high sputum EPX levels occurred in 27% of participants with blood eosinophil counts less than 150 cells/μL and 42% of participants with blood eosinophil counts between 150 and 299 cells/μL. Patients with persistently high sputum EPX values for 3 years were characterized by severe airflow obstruction, frequent exacerbations, and high mucus plug scores. In 59 patients with asthma who started mepolizumab during observation, serum EPX levels normalized in 96% but sputum EPX normalized in only 49%. Lung function remained abnormal even when sputum EPX normalized., Conclusions: Serum EPX is a valid protein biomarker of systemic eosinophilic inflammation in asthma, and sputum EPX levels are a more sensitive biomarker of airway eosinophilic inflammation than sputum eosinophil counts. Eosinophil measures in blood frequently miss airway eosinophilic inflammation, and mepolizumab frequently fails to normalize airway eosinophilic inflammation even though it invariably normalizes systemic eosinophilic inflammation., Competing Interests: Disclosure statement The study was supported by grants from the National Institutes of Health (grant nos. U10 HL109172, U10 HL109168, U10 HL109152, U10 HL109257, U10 HL109146, U10 HL109164, and U10 HL109086). The following companies provided financial support for study activities at the Coordinating and Clinical Centers beyond the third year of patient follow-up: AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Sanofi–Genzyme–Regeneron, and Teva. These companies had no role in study design or data analysis, and the only restriction on the funds was that they be used to support the SARP initiative. Disclosure of potential conflict of interest: M. Tang has participated in advisory boards with Sanofi. M. W. Johansson has received grants from Hoffmann-La Roche. N. N. Jarjour has received consulting fees from GlaxoSmithKline. L. C. Denlinger has received grants from the American Lung Association-Airway Clinical Research Centers (ALA-ACRC); has received consulting fees from OM Pharma; and has received study drugs for the PrecISE trial from GlaxoSmithKline, Laurel, Sun Pharma, Vifor/OM Pharma Vitaeris/CSL Behring, and Vitaflo. M. C. Peters is an employee and has stock in Gilead Sciences. M. Castro has received grants from the ALA-ACRC, Patient-Centered Outcomes Research Institute (PCORI), AstraZeneca, Gala Therapeutics, Genentech, GlaxoSmithKline, Novartis, Pulmatrix, Sanofi-Aventis, Shinogi, and Theravance; has received consulting fees from Genentech, Teva, Sanofi-Aventis, Merck, Novartis, Arrowhead Pharmaceuticals, Allakos, Amgen, OM Pharma, Pfizer, Pioneering Medicines, and GlaxoSmithKline; has received honoraria for presentations from Amgen, AstraZeneca, Genentech, Regeneron, Sanofi-Aventis, and Teva; and has stock in Aer Therapeutics. K. Sumino has participated in advisory boards with AstraZeneca. B. D. Levy has received grants from Pleris Pharmaceuticals; has received consulting fees from AstraZeneca, Gossamer Bio, Novartis, and Thetis Pharmaceuticals; and has stock ownership in Entrinsic Health and Nocion Therapeutics. E. Israel has received grants from AstraZeneca, Avillion, Gossamer Bio, and PCORI; has received royalties from UpToDate—Wolters Kluwer; has received consulting fees from AB Science, Allergy and Asthma Network, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Avillion, GlaxoSmithKline, Merck, National Heart, Lung, and Blood Institute, Pneuma Respiratory, PPS Health, Regeneron, Sanofi-Genzyme, Teva, and Cowen; has received honoraria for presentations to Westchester Medical Center; has received payment for expert testimony to Cambridge Medical Experts, Danager Lagnese, and SettlePou; has participated in an advisory board with Novartis; is an unpaid member of the coordinating committee for the National Asthma Education and Prevention Program; has stock in Vorso; and has received equipment and study drugs from Circassia, Genentech, Teva, Sun Pharma, Laurel Pharmaceuticals, Om Pharma, Nestle, CSL Behring, and Sanofi-Regeneron. W. Phipatanakul has received grants from Sanofi, Regeneron, GlaxoSmithKline, Genentech, and Novartis; has received consulting fees from Sanofi, Regeneron, GlaxoSmithKline, Genentech, Novartis, and AstraZeneca; and has received support for attending meetings/travel from Sanofi and Regeneron. S. E. Wenzel has received grants from Regeneron; has received consulting fees from Sanofi and Novartis; and has stock in Aer Therapeutics. P. G. Woodruff has received consulting fees from Roche, Sanofi, Regeneron, and AstraZeneca. J. V. Fahy has received consulting fees and has stock from Suzhou Connect Biopharmaceuticals, Ltd, and Aer Therapeutics; and has been issued two patents. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2024
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24. Eosinophils and tissue remodeling: Relevance to airway disease.
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Siddiqui S, Bachert C, Bjermer L, Buchheit KM, Castro M, Qin Y, Rupani H, Sagara H, Howarth P, and Taillé C
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- Humans, Eosinophils pathology, Airway Remodeling, Lung pathology, Chronic Disease, Nasal Polyps pathology, Rhinitis pathology, Asthma pathology, Respiration Disorders, Sinusitis pathology
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The ability of human tissue to reorganize and restore its existing structure underlies tissue homeostasis in the healthy airways, but in disease can persist without normal resolution, leading to an altered airway structure. Eosinophils play a cardinal role in airway remodeling both in health and disease, driving epithelial homeostasis and extracellular matrix turnover. Physiological consequences associated with eosinophil-driven remodeling include impaired lung function and reduced bronchodilator reversibility in asthma, and obstructed airflow in chronic rhinosinusitis with nasal polyps. Given the contribution of airway remodeling to the development and persistence of symptoms in airways disease, targeting remodeling is an important therapeutic consideration. Indeed, there is early evidence that eosinophil attenuation may reduce remodeling and disease progression in asthma. This review provides an overview of tissue remodeling in both health and airway disease with a particular focus on eosinophilic asthma and chronic rhinosinusitis with nasal polyps, as well as the role of eosinophils in these processes and the implications for therapeutic interventions. Areas for future research are also noted, to help improve our understanding of the homeostatic and pathological roles of eosinophils in tissue remodeling, which should aid the development of targeted and effective treatments for eosinophilic diseases of the airways., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) more...
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- 2023
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25. CCL5 is a potential bridge between type 1 and type 2 inflammation in asthma.
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Gauthier M, Kale SL, Oriss TB, Gorry M, Ramonell RP, Dalton K, Ray P, Fahy JV, Seibold MA, Castro M, Jarjour N, Gaston B, Bleecker ER, Meyers DA, Moore W, Hastie AT, Israel E, Levy BD, Mauger D, Erzurum S, Comhair SA, Wenzel SE, and Ray A more...
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- Animals, Humans, Mice, Chemokines metabolism, Eosinophils, Inflammation metabolism, Neutrophils, Sputum, Asthma, Chemokine CCL5 genetics, Chemokine CCL5 metabolism
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Background: Type 1 (T1) inflammation (marked by IFN-γ expression) is now consistently identified in subsets of asthma cohorts, but how it contributes to disease remains unclear., Objective: We sought to understand the role of CCL5 in asthmatic T1 inflammation and how it interacts with both T1 and type 2 (T2) inflammation., Methods: CCL5, CXCL9, and CXCL10 messenger RNA expression from sputum bulk RNA sequencing, as well as clinical and inflammatory data were obtained from the Severe Asthma Research Program III (SARP III). CCL5 and IFNG expression from bronchoalveolar lavage cell bulk RNA sequencing was obtained from the Immune Mechanisms in Severe Asthma (IMSA) cohort and expression related to previously identified immune cell profiles. The role of CCL5 in tissue-resident memory T-cell (TRM) reactivation was evaluated in a T1
high murine severe asthma model., Results: Sputum CCL5 expression strongly correlated with T1 chemokines (P < .001 for CXCL9 and CXCL10), consistent with a role in T1 inflammation. CCL5high participants had greater fractional exhaled nitric oxide (P = .009), blood eosinophils (P < .001), and sputum eosinophils (P = .001) in addition to sputum neutrophils (P = .001). Increased CCL5 bronchoalveolar lavage expression was unique to a previously described T1high /T2variable /lymphocytic patient group in the IMSA cohort, with IFNG trending with worsening lung obstruction only in this group (P = .083). In a murine model, high expression of the CCL5 receptor CCR5 was observed in TRMs and was consistent with a T1 signature. A role for CCL5 in TRM activation was supported by the ability of the CCR5 inhibitor maraviroc to blunt reactivation., Conclusion: CCL5 appears to contribute to TRM-related T1 neutrophilic inflammation in asthma while paradoxically also correlating with T2 inflammation and with sputum eosinophilia., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2023
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26. Bronchial epithelial cell transcriptional responses to inhaled corticosteroids dictate severe asthmatic outcomes.
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Ginebaugh SP, Hagner M, Ray A, Erzurum SC, Comhair SAA, Denlinger LC, Jarjour NN, Castro M, Woodruff PG, Christenson SA, Bleecker ER, Meyers DA, Hastie AT, Moore WC, Mauger DT, Israel E, Levy BD, Wenzel SE, and Camiolo MJ more...
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- Humans, Epithelial Cells metabolism, Adrenal Cortex Hormones therapeutic use, Quality of Life, Asthma drug therapy, Asthma genetics, Asthma diagnosis
- Abstract
Background: Inhaled corticosteroids (CSs) are the backbone of asthma treatment, improving quality of life, exacerbation rates, and mortality. Although effective for most, a subset of patients with asthma experience CS-resistant disease despite receiving high-dose medication., Objective: We sought to investigate the transcriptomic response of bronchial epithelial cells (BECs) to inhaled CSs., Methods: Independent component analysis was performed on datasets, detailing the transcriptional response of BECs to CS treatment. The expression of these CS-response components was examined in 2 patient cohorts and investigated in relation to clinical parameters. Supervised learning was used to predict BEC CS responses using peripheral blood gene expression., Results: We identified a signature of CS response that was closely correlated with CS use in patients with asthma. Participants could be separated on the basis of CS-response genes into groups with high and low signature expression. Patients with low expression of CS-response genes, particularly those with a severe asthma diagnosis, showed worse lung function and quality of life. These individuals demonstrated enrichment for T-lymphocyte infiltration in endobronchial brushings. Supervised machine learning identified a 7-gene signature from peripheral blood that reliably identified patients with poor CS-response expression in BECs., Conclusions: Loss of CS transcriptional responses within bronchial epithelium was related to impaired lung function and poor quality of life, particularly in patients with severe asthma. These individuals were identified using minimally invasive blood sampling, suggesting these findings may enable earlier triage to alternative treatments., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...
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- 2023
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27. The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: An overview of Network organization, procedures, and interventions.
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Georas SN, Wright RJ, Ivanova A, Israel E, LaVange LM, Akuthota P, Carr TF, Denlinger LC, Fajt ML, Kumar R, O'Neal WK, Phipatanakul W, Szefler SJ, Aronica MA, Bacharier LB, Burbank AJ, Castro M, Crotty Alexander L, Bamdad J, Cardet JC, Comhair SAA, Covar RA, DiMango EA, Erwin K, Erzurum SC, Fahy JV, Gaffin JM, Gaston B, Gerald LB, Hoffman EA, Holguin F, Jackson DJ, James J, Jarjour NN, Kenyon NJ, Khatri S, Kirwan JP, Kraft M, Krishnan JA, Liu AH, Liu MC, Marquis MA, Martinez F, Mey J, Moore WC, Moy JN, Ortega VE, Peden DB, Pennington E, Peters MC, Ross K, Sanchez M, Smith LJ, Sorkness RL, Wechsler ME, Wenzel SE, White SR, Zein J, Zeki AA, and Noel P more...
- Subjects
- Advisory Committees, Asthma diagnosis, Biomarkers, Clinical Protocols, Clinical Trials, Phase II as Topic, Humans, Research Design, Severity of Illness Index, Tomography, X-Ray Computed, Asthma drug therapy, Precision Medicine
- 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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2022
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28. Quantitative CT metrics are associated with longitudinal lung function decline and future asthma exacerbations: Results from SARP-3.
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Krings JG, Goss CW, Lew D, Samant M, McGregor MC, Boomer J, Bacharier LB, Sheshadri A, Hall C, Brownell J, Schechtman KB, Peterson S, McEleney S, Mauger DT, Fahy JV, Fain SB, Denlinger LC, Israel E, Washko G, Hoffman E, Wenzel SE, and Castro M more...
- Subjects
- Adult, Airway Remodeling, Asthma pathology, Asthma physiopathology, Disease Progression, Female, Forced Expiratory Volume, Humans, Lung pathology, Lung physiopathology, Male, Middle Aged, Prognosis, Tomography, X-Ray Computed, Asthma diagnostic imaging, Lung diagnostic imaging
- Abstract
Background: Currently, there is limited knowledge regarding which imaging assessments of asthma are associated with accelerated longitudinal decline in lung function., Objectives: We aimed to assess whether quantitative computed tomography (qCT) metrics are associated with longitudinal decline in lung function and morbidity in asthma., Methods: We analyzed 205 qCT scans of adult patients with asthma and calculated baseline markers of airway remodeling, lung density, and pointwise regional change in lung volume (Jacobian measures) for each participant. Using multivariable regression models, we then assessed the association of qCT measurements with the outcomes of future change in lung function, future exacerbation rate, and changes in validated measurements of morbidity., Results: Greater baseline wall area percent (β = -0.15 [95% CI = -0.26 to -0.05]; P < .01), hyperinflation percent (β = -0.25 [95% CI = -0.41 to -0.09]; P < .01), and Jacobian gradient measurements (cranial-caudal β = 10.64 [95% CI = 3.79-17.49]; P < .01; posterior-anterior β = -9.14, [95% CI = -15.49 to -2.78]; P < .01) were associated with more severe future lung function decline. Additionally, greater wall area percent (rate ratio = 1.06 [95% CI = 1.01-1.10]; P = .02) and air trapping percent (rate ratio =1.01 [95% CI = 1.00-1.02]; P = .03), as well as lower decline in the Jacobian determinant mean (rate ratio = 0.58 [95% CI = 0.41-0.82]; P < .01) and Jacobian determinant standard deviation (rate ratio = 0.52 [95% CI = 0.32-0.85]; P = .01), were associated with a greater rate of future exacerbations. However, imaging metrics were not associated with clinically meaningful changes in scores on validated asthma morbidity questionnaires., Conclusions: Baseline qCT measures of more severe airway remodeling, more small airway disease and hyperinflation, and less pointwise regional change in lung volumes were associated with future lung function decline and asthma exacerbations., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2021
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29. 2020 Updated Asthma Guidelines: Bronchial thermoplasty in the management of asthma.
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Castro M and Chupp G
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- Bronchi, Humans, Asthma therapy, Bronchial Thermoplasty
- Published
- 2021
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30. PrecISE: Precision Medicine in Severe Asthma: An adaptive platform trial with biomarker ascertainment.
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Israel E, Denlinger LC, Bacharier LB, LaVange LM, Moore WC, Peters MC, Georas SN, Wright RJ, Mauger DT, Noel P, Akuthota P, Bach J, Bleecker ER, Cardet JC, Carr TF, Castro M, Cinelli A, Comhair SAA, Covar RA, Alexander LC, DiMango EA, Erzurum SC, Fahy JV, Fajt ML, Gaston BM, Hoffman EA, Holguin F, Jackson DJ, Jain S, Jarjour NN, Ji Y, Kenyon NJ, Kosorok MR, Kraft M, Krishnan JA, Kumar R, Liu AH, Liu MC, Ly NP, Marquis MA, Martinez FD, Moy JN, O'Neal WK, Ortega VE, Peden DB, Phipatanakul W, Ross K, Smith LJ, Szefler SJ, Teague WG, Tulchinsky AF, Vijayanand P, Wechsler ME, Wenzel SE, White SR, Zeki AA, and Ivanova A more...
- Subjects
- Humans, Research Design, Asthma, Biomarkers, Precision Medicine, Randomized Controlled Trials as Topic
- 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., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2021
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31. Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways.
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Li X, Christenson SA, Modena B, Li H, Busse WW, Castro M, Denlinger LC, Erzurum SC, Fahy JV, Gaston B, Hastie AT, Israel E, Jarjour NN, Levy BD, Moore WC, Woodruff PG, Kaminski N, Wenzel SE, Bleecker ER, and Meyers DA more...
- Subjects
- Adult, Disease Progression, Genetic Association Studies, Humans, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sequence Analysis, RNA, Severity of Illness Index, Whole Genome Sequencing, Asthma genetics, Chromosomes, Human, Pair 17 genetics, Genotype, Neoplasm Proteins genetics, Respiratory Mucosa physiology
- Abstract
Background: The Chr17q12-21.2 region is the strongest and most consistently associated region with asthma susceptibility. The functional genes or single nucleotide polymorphisms (SNPs) are not obvious due to linkage disequilibrium., Objectives: We sought to comprehensively investigate whole-genome sequence and RNA sequence from human bronchial epithelial cells to dissect functional genes/SNPs for asthma severity in the Severe Asthma Research Program., Methods: Expression quantitative trait loci analysis (n = 114), correlation analysis (n = 156) of gene expression and asthma phenotypes, and pathway analysis were performed in bronchial epithelial cells and replicated. Genetic association for asthma severity (426 severe vs 531 nonsevere asthma) and longitudinal asthma exacerbations (n = 273) was performed., Results: Multiple SNPs in gasdermin B (GSDMB) associated with asthma severity (odds ratio, >1.25) and longitudinal asthma exacerbations (P < .05). Expression quantitative trait loci analyses identified multiple SNPs associated with expression levels of post-GPI attachment to proteins 3, GSDMB, or gasdermin A (3.1 × 10
-9 -4 ). Higher expression levels of GSDMB correlated with asthma and greater number of exacerbations (P < .05). Expression levels of GSDMB correlated with genes involved in IFN signaling, MHC class I antigen presentation, and immune system pathways (false-discovery rate-adjusted P < .05). rs1031458 and rs3902920 in GSDMB colocalized with IFN regulatory factor binding sites and associated with GSDMB expression, asthma severity, and asthma exacerbations (P < .05)., Conclusions: By using a unique set of gene expression data from lung cells obtained using bronchoscopy from comprehensively characterized subjects with asthma, we show that SNPs in GSDMB associated with asthma severity, exacerbations, and GSDMB expression levels. Furthermore, its expression levels correlated with asthma exacerbations and antiviral pathways. Thus, GSDMB is a functional gene for both asthma susceptibility and severity., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
more...- Published
- 2021
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32. Distinct associations of sputum and oral microbiota with atopic, immunologic, and clinical features in mild asthma.
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Durack J, Christian LS, Nariya S, Gonzalez J, Bhakta NR, Ansel KM, Beigelman A, Castro M, Dyer AM, Israel E, Kraft M, Martin RJ, Mauger DT, Peters SP, Rosenberg SR, Sorkness CA, Wechsler ME, Wenzel SE, White SR, Lynch SV, Boushey HA, and Huang YJ more...
- Subjects
- Administration, Inhalation, Adult, Asthma drug therapy, Biomarkers, Cytokines metabolism, Female, Humans, Hypersensitivity, Immediate drug therapy, Male, Treatment Outcome, Adrenal Cortex Hormones therapeutic use, Asthma microbiology, Hypersensitivity, Immediate microbiology, Microbiota genetics, Mouth microbiology, Sputum microbiology, Th2 Cells immunology
- Abstract
Background: Whether microbiome characteristics of induced sputum or oral samples demonstrate unique relationships to features of atopy or mild asthma in adults is unknown., Objective: We sought to determine sputum and oral microbiota relationships to clinical or immunologic features in mild atopic asthma and the impact on the microbiota of inhaled corticosteroid (ICS) treatment administered to ICS-naive subjects with asthma., Methods: Bacterial microbiota profiles were analyzed in induced sputum and oral wash samples from 32 subjects with mild atopic asthma before and after inhaled fluticasone treatment, 18 atopic subjects without asthma, and 16 nonatopic healthy subjects in a multicenter study (NCT01537133). Associations with clinical and immunologic features were examined, including markers of atopy, type 2 inflammation, immune cell populations, and cytokines., Results: Sputum bacterial burden inversely associated with bronchial expression of type 2 (T2)-related genes. Differences in specific sputum microbiota also associated with T2-low asthma phenotype, a subgroup of whom displayed elevations in lung inflammatory mediators and reduced sputum bacterial diversity. Differences in specific oral microbiota were more reflective of atopic status. After ICS treatment of patients with asthma, the compositional structure of sputum microbiota showed greater deviation from baseline in ICS nonresponders than in ICS responders., Conclusions: Novel associations of sputum and oral microbiota to immunologic features were observed in this cohort of subjects with or without ICS-naive mild asthma. These findings confirm and extend our previous report of reduced bronchial bacterial burden and compositional complexity in subjects with T2-high asthma, with additional identification of a T2-low subgroup with a distinct microbiota-immunologic relationship., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2020
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33. Baseline sputum eosinophil + neutrophil subgroups' clinical characteristics and longitudinal trajectories for NHLBI Severe Asthma Research Program (SARP 3) cohort.
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Hastie AT, Mauger DT, Denlinger LC, Coverstone A, Castro M, Erzurum S, Jarjour N, Levy BD, Meyers DA, Moore WC, Phillips B, Wenzel SE, Fahy JV, Israel E, and Bleecker ER
- Subjects
- Adult, Aged, Asthma pathology, Cohort Studies, Eosinophils pathology, Female, Humans, Male, Middle Aged, Neutrophils pathology, Asthma immunology, Eosinophils immunology, Neutrophils immunology, Sputum immunology
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- 2020
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34. Investigation of the relationship between IL-6 and type 2 biomarkers in patients with severe asthma.
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Li X, Hastie AT, Peters MC, Hawkins GA, Phipatanakul W, Li H, Moore WC, Busse WW, Castro M, Erzurum SC, Gaston B, Israel E, Jarjour NN, Levy BD, Wenzel SE, Meyers DA, Fahy JV, and Bleecker ER
- Subjects
- Adolescent, Adult, Asthma immunology, Biomarkers blood, Child, Female, Humans, Interleukin-6 immunology, Male, Severity of Illness Index, Asthma blood, Interleukin-6 blood
- Published
- 2020
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35. Severe asthma during childhood and adolescence: A longitudinal study.
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Ross KR, Gupta R, DeBoer MD, Zein J, Phillips BR, Mauger DT, Li C, Myers RE, Phipatanakul W, Fitzpatrick AM, Ly NP, Bacharier LB, Jackson DJ, Celedón JC, Larkin A, Israel E, Levy B, Fahy JV, Castro M, Bleecker ER, Meyers D, Moore WC, Wenzel SE, Jarjour NN, Erzurum SC, Teague WG, and Gaston B more...
- Subjects
- Adolescent, Child, Eosinophils, Female, Humans, Leukocyte Count, Longitudinal Studies, Male, Prospective Studies, Asthma blood, Asthma drug therapy, Asthma pathology, Severity of Illness Index
- Abstract
Background: Morbidity and mortality associated with childhood asthma are driven disproportionately by children with severe asthma. However, it is not known from longitudinal studies whether children outgrow severe asthma., Objective: We sought to study prospectively whether well-characterized children with severe asthma outgrow their asthma during adolescence., Methods: Children with asthma were assessed at baseline with detailed questionnaires, allergy tests, and lung function tests and were reassessed annually for 3 years. The population was enriched for children with severe asthma, as assessed by the American Thoracic Society/European Respiratory Society guidelines, and subject classification was reassessed annually., Results: At baseline, 111 (59%) children had severe asthma. Year to year, there was a decrease in the proportion meeting the criteria for severe asthma. After 3 years, only 30% of subjects met the criteria for severe asthma (P < .001 compared with enrollment). Subjects experienced improvements in most indices of severity, including symptom scores, exacerbations, and controller medication requirements, but not lung function. Surprisingly, boys and girls were equally likely to has resolved asthma (33% vs 29%). The odds ratio in favor of resolution of severe asthma was 2.75 (95% CI, 1.02-7.43) for those with a peripheral eosinophil count of greater than 436 cells/μL., Conclusions: In longitudinal analysis of this well-characterized cohort, half of the children with severe asthma no longer had severe asthma after 3 years; there was a stepwise decrease in the proportion meeting severe asthma criteria. Surprisingly, asthma severity decreased equally in male and female subjects. Peripheral eosinophilia predicted resolution. These data will be important for planning clinical trials in this population., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2020
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36. Development and initial validation of the Asthma Severity Scoring System (ASSESS).
- Author
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Fitzpatrick AM, Szefler SJ, Mauger DT, Phillips BR, Denlinger LC, Moore WC, Sorkness RL, Wenzel SE, Gergen PJ, Bleecker ER, Castro M, Erzurum SC, Fahy JV, Gaston BM, Israel E, Levy BD, Meyers DA, Teague WG, Bacharier LB, Ly NP, Phipatanakul W, Ross KR, Zein J, and Jarjour NN more...
- Subjects
- Adolescent, Adult, Child, Female, Humans, Male, Asthma drug therapy, Asthma pathology, Severity of Illness Index, Triamcinolone administration & dosage
- Abstract
Background: Tools for quantification of asthma severity are limited., Objective: We sought to develop a continuous measure of asthma severity, the Asthma Severity Scoring System (ASSESS), for adolescents and adults, incorporating domains of asthma control, lung function, medications, and exacerbations., Methods: Baseline and 36-month longitudinal data from participants in phase 3 of the Severe Asthma Research Program (NCT01606826) were used. Scale properties, responsiveness, and a minimally important difference were determined. External replication was performed in participants enrolled in the Severe Asthma Research Program phase 1/2. The utility of ASSESS for detecting treatment response was explored in participants undergoing corticosteroid responsiveness testing with intramuscular triamcinolone and participants receiving biologics., Results: ASSESS scores ranged from 0 to 20 (8.78 ± 3.9; greater scores reflect worse severity) and differed among 5 phenotypic groups. Measurement properties were acceptable. ASSESS was responsive to changes in quality of life with a minimally important difference of 2, with good specificity for outcomes of asthma improvement and worsening but poor sensitivity. Replication analyses yielded similar results, with a 2-point decrease (improvement) associated with improvements in quality of life. Participants with a 2-point or greater decrease (improvement) in ASSESS scores also had greater improvement in lung function and asthma control after triamcinolone, but these differences were limited to phenotypic clusters 3, 4, and 5. Participants treated with biologics also had a 2-point or greater decrease (improvement) in ASSESS scores overall., Conclusions: The ASSESS tool is an objective measure that might be useful in epidemiologic and clinical research studies for quantification of treatment response in individual patients and phenotypic groups. However, validation studies are warranted., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. All rights reserved.) more...
- Published
- 2020
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37. Exacerbation-prone asthma in the context of race and ancestry in Asthma Clinical Research Network trials.
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Grossman NL, Ortega VE, King TS, Bleecker ER, Ampleford EA, Bacharier LB, Cabana MD, Cardet JC, Carr TF, Castro M, Denlinger LC, Denson JL, Fandino N, Fitzpatrick AM, Hawkins GA, Holguin F, Krishnan JA, Lazarus SC, Nyenhuis SM, Phipatanakul W, Ramratnam SK, Wenzel S, Peters SP, Meyers DA, Wechsler ME, and Israel E more...
- Subjects
- Adult, Humans, Male, Middle Aged, Risk Factors, Black or African American, Asthma ethnology, Asthma genetics, Registries, Self Report, White People
- Abstract
Background: Minority groups of African descent experience disproportionately greater asthma morbidity compared with other racial groups, suggesting that genetic variation from a common ancestry could influence exacerbation risk., Objective: We evaluated clinical trial measures in the context of self-reported race and genetic ancestry to identify risk factors for asthma exacerbations., Methods: One thousand eight hundred forty multiethnic subjects from 12 Asthma Clinical Research Network and AsthmaNet trials were analyzed for incident asthma exacerbations with Poisson regression models that included clinical measures, self-reported race (black, non-Hispanic white, and other), and estimates of global genetic African ancestry in a subgroup (n = 760)., Results: Twenty-four percent of 1840 subjects self-identified as black. Black and white subjects had common risk factors for exacerbations, including a history of 2 or more exacerbations in the previous year and FEV
1 percent predicted values, whereas chronic sinusitis, allergic rhinitis, and gastroesophageal reflux disease were only associated with increased exacerbation risk in black subjects. In the combined multiethnic cohort, neither race (P = .30) nor percentage of genetic African ancestry as a continuous variable associated with exacerbation risk (adjusted rate ratio [RR], 1.26 [95% CI, 0.94-1.70; P = .13]; RR per 1-SD change [32% ancestry], 0.97 [95% CI, 0.78-1.19; P = .74]). However, in 161 black subjects with genetic data, those with African ancestry greater than the median (≥82%) had a significantly greater risk of exacerbation (RR, 3.06 [95% CI, 1.09-8.6; P = .03])., Conclusion: Black subjects have unique risk factors for asthma exacerbations, of which global African genetic ancestry had the strongest effect., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2019
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38. Reply.
- Author
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Cardet JC, Jiang X, Lu Q, Gerard N, McIntire K, Boushey HA, Castro M, Chinchilli VM, Codispoti CD, Dyer AM, Holguin F, Kraft M, Lazarus S, Lemanske RF, Lugogo N, Mauger D, Moore WC, Moy J, Ortega VE, Peters SP, Smith LJ, Solway J, Sorkness CA, Sumino K, Wechsler ME, Wenzel S, and Israel E more...
- Subjects
- Adrenergic beta-Antagonists, Bronchodilator Agents, Alendronate, Lung drug effects
- Published
- 2019
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39. Harmonized outcome measures for use in asthma patient registries and clinical practice.
- Author
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Gliklich RE, Castro M, Leavy MB, Press VG, Barochia A, Carroll CL, Harris J, Rittner SS, Freishtat R, Panettieri RA Jr, and Mosnaim GS
- Subjects
- Adult, Child, Humans, Patient Reported Outcome Measures, Asthma, Registries
- Abstract
Background: Asthma, a common chronic airway disorder, affects an estimated 25 million persons in the United States and 330 million persons worldwide. Although many asthma patient registries exist, the ability to link and compare data across registries is hindered by a lack of harmonization in the outcome measures collected by each registry., Objectives: The purpose of this project was to develop a minimum set of patient- and provider-relevant standardized outcome measures that could be collected in asthma patient registries and clinical practice., Methods: Asthma registries were identified through multiple sources and invited to join the workgroup and submit outcome measures. Additional measures were identified through literature searches and reviews of quality measures and consensus statements. Outcome measures were categorized by using the Agency for Healthcare Research and Quality's supported Outcome Measures Framework. A minimum set of broadly relevant measures was identified. Measure definitions were harmonized through in-person and virtual meetings., Results: Forty-six outcome measures, including those identified from 13 registries, were curated and harmonized into a minimum set of 21 measures in the Outcome Measures Framework categories of survival, clinical response, events of interest, patient-reported outcomes, resource utilization, and experience of care. The harmonized definitions build on existing consensus statements and are appropriate for adult and pediatric patients., Conclusions: The harmonized measures represent a minimum set of outcomes that are relevant in asthma research and clinical practice. Routine and consistent collection of these measures in registries and other systems would support creation of a national research infrastructure to efficiently address new questions and improve patient management and outcomes., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. All rights reserved.) more...
- Published
- 2019
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40. Loss of bronchoprotection with ICS plus LABA treatment, β-receptor dynamics, and the effect of alendronate.
- Author
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Cardet JC, Jiang X, Lu Q, Gerard N, McIntire K, Boushey HA, Castro M, Chinchilli VM, Codispoti CD, Dyer AM, Holguin F, Kraft M, Lazarus S, Lemanske RF, Lugogo N, Mauger D, Moore WC, Moy J, Ortega VE, Peters SP, Smith LJ, Solway J, Sorkness CA, Sumino K, Wechsler ME, Wenzel S, and Israel E more...
- Subjects
- Administration, Inhalation, Adult, Double-Blind Method, Female, Humans, Male, Proof of Concept Study, Adrenal Cortex Hormones administration & dosage, Alendronate administration & dosage, Asthma drug therapy, Asthma pathology, Asthma physiopathology, Fluticasone administration & dosage, Receptors, Adrenergic, beta-2 metabolism, Salmeterol Xinafoate administration & dosage
- Abstract
Background: Loss of bronchoprotection (LOBP) with a regularly used long-acting β
2 -adrenergic receptor agonist (LABA) is well documented. LOBP has been attributed to βript>2 -adrenergic receptor (B2AR) downregulation, a process requiring farnesylation, which is inhibited by alendronate., Objective: We sought to determine whether alendronate can reduce LABA-associated LOBP in inhaled corticosteroid (ICS)-treated patients., Methods: We conducted a randomized, double-blind, placebo-controlled, parallel-design, proof-of-concept trial. Seventy-eight participants with persistent asthma receiving 250 μg of fluticasone twice daily for 2 weeks were randomized to receive alendronate or placebo while initiating salmeterol for 8 weeks. Salmeterol-protected methacholine challenges (SPMChs) and PBMC B2AR numbers (radioligand binding assay) and signaling (cyclic AMP ELISA) were assessed before randomization and after 8 weeks of ICS plus LABA treatment. LOBP was defined as a more than 1 doubling dose reduction in SPMCh PC 20 value., Results: The mean doubling dose reduction in SPMCh PC20 value was 0.50 and 0.27 with alendronate and placebo, respectively (P = .62). Thirty-eight percent of participants receiving alendronate and 33% receiving placebo had LOBP (P = .81). The after/before ICS plus LABA treatment ratio of B2AR number was 1.0 for alendronate (P = .86) and 0.8 for placebo (P = .15; P = .31 for difference between treatments). The B2AR signaling ratio was 0.89 for alendronate (P = .43) and 1.02 for placebo (P = .84; P = .44 for difference). Changes in lung function and B2AR number and signaling were similar between those who did and did not experience LOBP., Conclusion: This study did not find evidence that alendronate reduces LABA-associated LOBP, which relates to the occurrence of LOBP in only one third of participants. LOBP appears to be less common than presumed in concomitant ICS plus LABA-treated asthmatic patients. B2AR downregulation measured in PBMCs does not appear to reflect LOBP., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2019
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41. Racial disparities in asthma-related health care use in the National Heart, Lung, and Blood Institute's Severe Asthma Research Program.
- Author
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Fitzpatrick AM, Gillespie SE, Mauger DT, Phillips BR, Bleecker ER, Israel E, Meyers DA, Moore WC, Sorkness RL, Wenzel SE, Bacharier LB, Castro M, Denlinger LC, Erzurum SC, Fahy JV, Gaston BM, Jarjour NN, Larkin A, Levy BD, Ly NP, Ortega VE, Peters SP, Phipatanakul W, Ramratnam S, and Teague WG more...
- Subjects
- Adolescent, Adult, Black or African American, Emergency Service, Hospital statistics & numerical data, Female, Humans, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), United States, White People, Young Adult, Asthma ethnology, Asthma therapy, Patient Acceptance of Health Care ethnology
- Abstract
Background: Despite advances in asthma care, disparities persist. Black patients are disproportionally affected by asthma and also have poorer outcomes compared with white patients., Objective: We sought to determine associations between black and white patients and asthma-related health care use, accounting for complex relationships., Methods: This study was completed as part of the National Heart, Lung, and Blood Institute's Severe Asthma Research Program, a prospective observational cohort. Between November 2012 and February 2015, it enrolled 579 participants 6 years and older with 1 year of observation time and complete data. Inverse probability of treatment weighting was used to balance racial groups with respect to community and family socioeconomic variables and environmental exposure variables. The primary outcome was emergency department (ED) use for asthma. Secondary outcomes included inhaled corticosteroid use, outpatient physician's office visits for asthma, and asthma-related hospitalization., Results: Black patients had greater odds of ED use over 1 year (odds ratio, 2.19; 95% CI, 1.43-3.35) but also differed in the majority (>50%) of baseline variables measured. After statistical balancing of the racial groups, the difference between black and white patients with respect to ED use no longer reached the level of significance. Instead, in secondary analyses black patients were less likely to see an outpatient physician for asthma management (adjusted odds ratio, 0.57; 95% CI, 0.38-0.85)., Conclusions: The disparity in ED use was eliminated after consideration of multiple variables. Social and environmental policies and interventions tailored to black populations with a high burden of asthma are critical to reduction (or elimination) of these disparities., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2019
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42. Challenges in assessing the efficacy of systemic corticosteroids for severe wheezing episodes in preschool children.
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Guilbert TW, Bacharier LB, Mauger DT, Phipatanakul W, Szefler SJ, Boehmer S, Beigelman A, Fitzpatrick AM, Jackson DJ, Baxi SN, Benson M, Burnham CD, Cabana MD, Castro M, Chmiel JF, Covar R, Daines M, Gaffin JM, Gentile DA, Holguin F, Israel E, Kelly HW, Lazarus SC, Lemanske RF Jr, Ly N, Meade K, Morgan W, Moy J, Olin JT, Peters SP, Pongracic JA, Raissy HH, Ross K, Sheehan WJ, Sorkness C, Teague WG, Thyne S, and Martinez FD more...
- Subjects
- Administration, Inhalation, Adrenal Cortex Hormones, Child, Preschool, Humans, Asthma, Respiratory Sounds
- Published
- 2019
- Full Text
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43. Performance of the Asthma Impact on Quality of Life Scale (A-IQOLS) in diverse asthma research populations and demographic subgroups.
- Author
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Wilson SR, Wise RA, Castro M, Mulligan MJ, Ayala E, Chausow A, Huang Q, and Gummidipundi S
- Subjects
- Adolescent, Adult, Female, Humans, Male, Middle Aged, Psychometrics, Asthma epidemiology, Asthma psychology, Quality of Life, Self Report, Surveys and Questionnaires
- Abstract
Background: The Asthma Impact on Quality of Life Scale (A-IQOLS) assesses the patient-perceived negative effect of asthma on quality of life. Its standard error of measurement is known; it has strong construct, convergent, and divergent validity; and it provides information that is unique among asthma outcome measures., Objective: We sought to characterize the psychometric properties of the A-IQOLS and its suitability for use in demographically and clinically diverse adult asthmatic populations., Methods: Data from participants in 5 independent asthma studies, with samples ranging from patients with well-controlled moderate asthma to patients with severe poorly controlled asthma, were pooled to determine the psychometric performance of A-IQOLS scores overall and in multiple demographic, disease status, and study subgroups., Results: Pooled sample (n = 597) age averaged 45 years; 66% were female, 65% were white, 22% were African American, 11% were Hispanic, and 11% had a high school education or less. The rated importance of its underlying life dimensions and associations between A-IQOLS scores and lung function, symptom, Asthma Control Test, Juniper Mini Asthma Quality of Life Questionnaire, and Marks Asthma Quality of Life Questionnaire scores was very similar, regardless of patients' demographic and clinical characteristics. A-IQOLS scores discriminated among the individual study samples, as well as other patient-reported symptom and functional status measures. Distribution and anchor-based considerations suggest an A-IQOLS minimum clinically important difference in the vicinity of 0.50 and not less than 0.33 scale score units., Conclusions: A-IQOLS is valid for research and potentially clinical use in demographically and clinically diverse patients., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2019
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44. Refractory airway type 2 inflammation in a large subgroup of asthmatic patients treated with inhaled corticosteroids.
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Peters MC, Kerr S, Dunican EM, Woodruff PG, Fajt ML, Levy BD, Israel E, Phillips BR, Mauger DT, Comhair SA, Erzurum SC, Johansson MW, Jarjour NN, Coverstone AM, Castro M, Hastie AT, Bleecker ER, Wenzel SE, and Fahy JV more...
- Subjects
- Administration, Inhalation, Adult, Biomarkers blood, Eosinophils immunology, Eosinophils metabolism, Eosinophils pathology, Female, Gene Expression Regulation immunology, Humans, Immunoglobulin E blood, Immunoglobulin E immunology, Inflammation blood, Inflammation immunology, Leukocyte Count, Longitudinal Studies, Male, Middle Aged, Th2 Cells immunology, Th2 Cells metabolism, Adrenal Cortex Hormones administration & dosage, Asthma blood, Asthma drug therapy, Asthma immunology, Cytokines blood, Cytokines immunology, Gene Expression Regulation drug effects
- Abstract
Background: Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients receiving high-dose inhaled corticosteroids (ICSs) is uncertain., Objective: We sought to determine whether airway type 2 inflammation persists in patients treated with ICSs and to evaluate the clinical features of patients with steroid-resistant airway type 2 inflammation., Methods: We used quantitative PCR to generate a composite metric of type 2 cytokine gene expression (type 2 gene mean [T2GM]) in induced sputum cells from healthy control subjects, patients with severe asthma receiving ICSs (n = 174), and patients with nonsevere asthma receiving ICSs (n = 85). We explored relationships between asthma outcomes and T2GM values and the utility of noninvasive biomarkers of airway T2GM., Results: Sputum cell T2GM values in asthmatic patients were significantly increased and remained high after treatment with intramuscular triamcinolone. We used the median T2GM value as a cutoff to classify steroid-treated type 2-low and steroid-resistant type 2-high (srT2-high) subgroups. Compared with patients with steroid-treated type 2-low asthma, those with srT2-high asthma were older and had more severe asthma. Blood eosinophil cell counts predicted srT2-high asthma when body mass index was less than 40 kg/m
2 but not when it was 40 kg/m2 or greater, whereas blood IgE levels strongly predicted srT2-high asthma when age was less than 34 years but not when it was 34 years or greater., Conclusion: Despite ICS therapy, many asthmatic patients have persistent airway type 2 inflammation (srT2-high asthma), and these patients are older and have more severe disease. Body weight and age modify the performance of blood-based biomarkers of airway type 2 inflammation., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2019
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45. Lumen area change (Delta Lumen) between inspiratory and expiratory multidetector computed tomography as a measure of severe outcomes in asthmatic patients.
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Shim SS, Schiebler ML, Evans MD, Jarjour N, Sorkness RL, Denlinger LC, Rodriguez A, Wenzel S, Hoffman EA, Lin CL, Gierada DS, Castro M, and Fain SB
- Subjects
- Adrenal Cortex Hormones therapeutic use, Adult, Airway Remodeling, Asthma drug therapy, Asthma pathology, Asthma physiopathology, Female, Humans, Male, Middle Aged, Multidetector Computed Tomography, Respiration, Respiratory Function Tests, Respiratory System pathology, Respiratory System physiopathology, Young Adult, Asthma diagnostic imaging, Respiratory System diagnostic imaging
- Abstract
Background: Quantitative computed tomographic (QCT) biomarkers of airway morphology hold potential for understanding and monitoring regional airway remodeling in asthmatic patients., Objective: We sought to determine whether the change in airway lumen area between total lung capacity (TLC) and functional residual capacity (FRC) lung volumes measured from CT imaging data was correlated with severe outcomes in asthmatic patients., Methods: We studied 152 asthmatic patients (90 female and 62 male patients) and 33 healthy subjects (12 female and 21 male subjects) using QCT. Postprocessing of airways at generations 1 to 5 (1 = trachea) was performed for wall area percentage, wall thickness percentage (WT%), lumen area at baseline total lung capacity (LA
TLC ), lumen area at baseline functional residual capacity (LAFRC ), and low attenuation area at FRC. A new metric (reflecting remodeling, distal air trapping, or both), Delta Lumen, was determined as follows: Percentage difference in lumen area (LATLC - LAFRC )/LATLC × 100., Results: Postprocessing of 4501 airway segments was performed (3681 segments in the 152 patients with asthma and 820 segments in the 33 healthy subjects; range, 17-28 segments per subject). Delta Lumen values were negatively correlated with WT% and low attenuation area (P < .01) in asthmatic patients. Delta Lumen values were significantly lower for airway generations 3 to 5 (segmental airways) in subjects undergoing hospitalization because of exacerbation and in patients with refractory asthma requiring treatment with systemic corticosteroids. WT% and low attenuation area were positively and Delta Lumen values were negatively associated with systemic corticosteroid treatment (P < .05), suggesting that a reduced Delta Lumen value is a potential outcome biomarker in patients with severe asthma., Conclusion: Reduced Delta Lumen value in the central airways measured by using QCT is a promising exploratory biomarker of unstable refractory asthma that warrants further study., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2018
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46. Recurrent wheezing in children following human metapneumovirus infection.
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Coverstone AM, Wilson B, Burgdorf D, Schechtman KB, Storch GA, Holtzman MJ, Castro M, Bacharier LB, and Sumino K
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- Child, Preschool, Cohort Studies, Female, Humans, Infant, Male, Metapneumovirus, Prospective Studies, Paramyxoviridae Infections complications, Respiratory Sounds etiology, Respiratory Tract Infections complications, Respiratory Tract Infections virology
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- 2018
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47. A new measure to assess asthma's effect on quality of life from the patient's perspective.
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Wilson SR, Mulligan MJ, Ayala E, Chausow A, Huang Q, Knowles SB, Gummidipundi S, Castro M, and Wise RA
- Subjects
- Adolescent, Adult, Chronic Disease, Female, Humans, Male, Middle Aged, Psychometrics, Spirometry, Asthma physiopathology, Asthma psychology, Quality of Life
- Abstract
Background: The Asthma Impact on Quality of Life Scale (A-IQOLS) assesses the negative effect of asthma on quality of life (QoL) from the patient's perspective by using dimensions of Flanagan's Quality of Life Scale (QOLS), a measure of current QoL., Objectives: We sought to determine and compare the psychometric properties of the A-IQOLS and QOLS, including their sensitivities to differences and change in asthma status., Methods: In a test-retest design (3- to 5-week interval) adults with persistent asthma underwent spirometry and were administered the A-IQOLS, other asthma outcome measures (Asthma Control Test, Asthma Symptom Utility Index, and the Marks and Juniper Asthma Quality of Life Questionnaires), and the QOLS., Results: Participants' (n = 147) mean age was 49 years, 76% were white, 12% were Hispanic, and 65% were female. A-IQOLS and QOLS scores were significantly correlated with other asthma outcomes scores, except FEV
1 , but shared relatively low common variance with these measures. A-IQOLS but not QOLS score changes were significantly correlated with changes in asthma outcomes. An A-IQOLS standard error of measurement of 0.27 implies that a within-person score change of ±0.73 or greater constitutes a true change. The QOLS standard error of measurement was 0.43., Conclusions: A-IQOLS provides a reliable, valid, and unique assessment of the patient-perceived negative effect of asthma on QoL that is suitable for use in asthma clinical research and potentially in clinical care. Further studies are needed in diverse patient populations. QOLS, a measure of current QoL, is less sensitive to disease status changes but might be useful in characterizing study populations, in treatment adherence research, and as a clinical and research tool in patients with multiple, severe, and/or life-limiting chronic conditions., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2018
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48. Obesity's effect on asthma extends to diagnostic criteria.
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Lugogo N, Green CL, Agada N, Zhang S, Meghdadpour S, Zhou R, Yang S, Anstrom KJ, Israel E, Martin R, Lemanske RF Jr, Boushey H, Lazarus SC, Wasserman SI, Castro M, Calhoun W, Peters SP, DiMango E, Chinchilli V, Kunselman S, King TS, Icitovic N, and Kraft M more...
- Subjects
- Adult, Biomarkers blood, Eosinophils metabolism, Female, Humans, Immunoglobulin E blood, Inflammation blood, Leukocyte Count, Male, Middle Aged, Nitric Oxide blood, Asthma blood, Asthma diagnosis, Obesity blood, Obesity diagnosis
- Abstract
Background: The use of inflammatory biomarkers to delineate the type of lung inflammation present in asthmatic subjects is increasingly common. However, the effect of obesity on these markers is unknown., Objectives: We aimed to determine the effect of obesity on conventional markers of inflammation in asthmatic subjects., Methods: We performed secondary analysis of data from 652 subjects previously enrolled in 2 Asthma Clinical Research Network trials. We performed linear correlations between biomarkers and logistic regression analysis to determine the predictive value of IgE levels, blood eosinophil counts, and fraction of exhaled nitric oxide values in relationship to sputum eosinophil counts (>2%), as well as to determine whether cut points existed that would maximize the sensitivity and specificity for predicting sputum eosinophilia in the 3 weight groups., Results: Overall, statistically significant but relatively weak correlations were observed among all 4 markers of inflammation. Within obese subjects, the only significant correlation found was between IgE levels and blood eosinophil counts (r = 0.33, P < .001); furthermore, all other correlations between inflammatory markers were approximately 0, including correlations with sputum eosinophil counts. In addition, the predictive value of each biomarker alone or in combination was poor in obese subjects. In fact, in obese subjects none of the biomarkers of inflammation significantly predicted the presence of high sputum eosinophil counts. Obese asthmatic subjects have lower cut points for IgE levels (268 IU), fraction of exhaled nitric oxide values (14.5 ppb), and blood eosinophil counts (96 cells/μL) than all other groups., Conclusions: In obese asthmatic subjects conventional biomarkers of inflammation are poorly predictive of eosinophilic airway inflammation. As such, biomarkers currently used to delineate eosinophilic inflammation in asthmatic subjects should be approached with caution in these subjects., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2018
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49. Income is an independent risk factor for worse asthma outcomes.
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Cardet JC, Louisias M, King TS, Castro M, Codispoti CD, Dunn R, Engle L, Giles BL, Holguin F, Lima JJ, Long D, Lugogo N, Nyenhuis S, Ortega VE, Ramratnam S, Wechsler ME, Israel E, and Phipatanakul W
- Subjects
- Adult, Asthma economics, Asthma therapy, Double-Blind Method, Female, Humans, Male, Middle Aged, Risk Factors, Socioeconomic Factors, Asthma mortality, Income
- Abstract
Background: Socioeconomic status (SES) is associated with asthma morbidity in observational studies, but the factors underlying this association are uncertain., Objective: We investigated whether 3 SES correlates-low income, low education, and high perceived stress-were independent risk factors for treatment failure and asthma exacerbations in the context of a randomized controlled trial., Methods: The effect of low SES (household income of <$50,000/y and household educational level of less than a Bachelor's degree) and high perceived stress (defined as a score of >20 on a perceived stress scale) on asthma morbidity was analyzed in 381 participants by using Poisson regression models. The primary outcome was treatment failure (defined in the trial protocol as a significant clinical or airflow deterioration), and the secondary outcome was asthma exacerbations requiring systemic corticosteroids., Results: Fifty-four percent of participants had a low income, 40% had a low educational level, and 17% had high perceived stress levels. Even after adjusting for race and other important confounders, participants with lower income had higher rates of both treatment failures (rate ratio, 1.6; 95% CI, 1.1-2.3; P = .03) and exacerbations (rate ratio, 1.9; 95% CI, 1.1-3.3; P = .02). Adherence with inhaled corticosteroids was similarly high for both income categories. Education and perceived stress were not significantly associated with either outcome., Conclusions: In the context of a randomized controlled trial, participants with lower income were more likely to experience adverse asthma outcomes independent of education, perceived stress, race, and medication adherence., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2018
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50. Quantitative computed tomographic imaging-based clustering differentiates asthmatic subgroups with distinctive clinical phenotypes.
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Choi S, Hoffman EA, Wenzel SE, Castro M, Fain S, Jarjour N, Schiebler ML, Chen K, and Lin CL
- Subjects
- Adult, Asthma pathology, Cluster Analysis, Female, Humans, Male, Middle Aged, Phenotype, Principal Component Analysis, Severity of Illness Index, Tomography, X-Ray Computed, Young Adult, Asthma classification, Asthma diagnostic imaging
- Abstract
Background: Imaging variables, including airway diameter, wall thickness, and air trapping, have been found to be important metrics when differentiating patients with severe asthma from those with nonsevere asthma and healthy subjects., Objective: The objective of this study was to identify imaging-based clusters and to explore the association of the clusters with existing clinical metrics., Methods: We performed an imaging-based cluster analysis using quantitative computed tomography-based structural and functional variables extracted from the respective inspiration and expiration scans of 248 asthmatic patients. The imaging-based metrics included a broader set of multiscale variables, such as inspiratory airway dimension, expiratory air trapping, and registration-based lung deformation (inspiration vs expiration). Asthma subgroups derived from a clustering method were associated with subject demographics, questionnaire results, medication history, and biomarker variables., Results: Cluster 1 was composed of younger patients with early-onset nonsevere asthma and reversible airflow obstruction and normal airway structure. Cluster 2 was composed of patients with a mix of patients with nonsevere and severe asthma with marginal inflammation who exhibited airway luminal narrowing without wall thickening. Clusters 3 and 4 were dominated by patients with severe asthma. Cluster 3 patients were obese female patients with reversible airflow obstruction who exhibited airway wall thickening without airway narrowing. Cluster 4 patients were late-onset older male subjects with persistent airflow obstruction who exhibited significant air trapping and reduced regional deformation. Cluster 3 and 4 patients also showed decreased lymphocyte and increased neutrophil counts, respectively., Conclusions: Four image-based clusters were identified and shown to be correlated with clinical characteristics. Such clustering serves to differentiate asthma subgroups that can be used as a basis for the development of new therapies., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2017
- Full Text
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