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  1. Article: Tezepelumab for Severe Asthma: One Drug Targeting Multiple Disease Pathways and Patient Types.

    Panettieri, Reynold / Lugogo, Njira / Corren, Jonathan / Ambrose, Christopher S

    Journal of asthma and allergy

    2024  Volume 17, Page(s) 219–236

    Abstract: Asthma is a heterogeneous inflammatory disease of the airways, affecting many children, adolescents, and adults worldwide. Up to 10% of people with asthma have severe disease, associated with a higher risk of hospitalizations, greater healthcare costs, ... ...

    Abstract Asthma is a heterogeneous inflammatory disease of the airways, affecting many children, adolescents, and adults worldwide. Up to 10% of people with asthma have severe disease, associated with a higher risk of hospitalizations, greater healthcare costs, and poorer outcomes. Patients with severe asthma generally require high-dose inhaled corticosteroids and additional controller medications to achieve disease control; however, many patients remain uncontrolled despite this intensive treatment. The treatment of severe uncontrolled asthma has improved with greater understanding of asthma pathways and phenotypes as well as the advent of targeted biologic therapies. Tezepelumab, a monoclonal antibody, blocks thymic stromal lymphopoietin, an epithelial cytokine that has multifaceted effects on the initiation and persistence of asthma inflammation and pathophysiology. Unlike other biologic treatments, tezepelumab has demonstrated efficacy across severe asthma phenotypes, with the magnitude of effects varying by phenotype. Here we describe the anti-inflammatory effects and efficacy of tezepelumab across the most relevant phenotypes of severe asthma. Across clinical studies, tezepelumab reduced annualized asthma exacerbation rates versus placebo by 63-71% in eosinophilic severe asthma, by 58-68% in allergic severe asthma, by 67-71% in allergic and eosinophilic severe asthma, by 34-49% in type 2-low asthma, and by 31-41% in oral corticosteroid-dependent asthma. Furthermore, in all these asthma phenotypes, tezepelumab demonstrated higher efficacy in reducing exacerbations requiring hospitalizations or emergency department visits versus placebo. In patients with severe uncontrolled asthma, who commonly have multiple drivers of inflammation and disease, tezepelumab may modulate airway inflammation more extensively, as other available biologics block only specific downstream components of the inflammatory cascade.
    Language English
    Publishing date 2024-03-19
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2494877-9
    ISSN 1178-6965
    ISSN 1178-6965
    DOI 10.2147/JAA.S342391
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Is it RSV?

    Ambrose, Christopher S

    Health science reports

    2018  Volume 1, Issue 12, Page(s) e97

    Abstract: A study of infant bronchiolitis-coded episodes described the proportion of events attributable to respiratory syncytial virus (RSV) and demonstrated that episodes occurring during the peak months of winter viral season, among younger infants, and among ... ...

    Abstract A study of infant bronchiolitis-coded episodes described the proportion of events attributable to respiratory syncytial virus (RSV) and demonstrated that episodes occurring during the peak months of winter viral season, among younger infants, and among those with higher levels of care, were more likely to be attributable to RSV.
    Language English
    Publishing date 2018-10-12
    Publishing country United States
    Document type Journal Article
    ISSN 2398-8835
    ISSN (online) 2398-8835
    DOI 10.1002/hsr2.97
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Statistical Power to Detect an Association Between Guideline-based Palivizumab Administration and Hospitalizations for Respiratory Syncytial Virus Infections.

    Ambrose, Christopher S

    The Pediatric infectious disease journal

    2017  Volume 36, Issue 3, Page(s) 348

    MeSH term(s) Antibodies, Monoclonal ; Antiviral Agents ; Hospitalization ; Humans ; Infant ; Palivizumab ; Respiratory Syncytial Virus Infections
    Chemical Substances Antibodies, Monoclonal ; Antiviral Agents ; Palivizumab (DQ448MW7KS)
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 392481-6
    ISSN 1532-0987 ; 0891-3668
    ISSN (online) 1532-0987
    ISSN 0891-3668
    DOI 10.1097/INF.0000000000001432
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: At-home asthma mortality unchanged despite declining mortality in other settings: US death certificate data (2000-2019).

    Kilpatrick, Karynsa / Ambrose, Christopher S / Lindsley, Andrew W / Oppenheimer, John

    Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology

    2023  Volume 132, Issue 2, Page(s) 216–222

    Abstract: Background: Asthma mortality rates in the United States have declined since 1999; however, asthma mortality by place of death has not been comprehensively evaluated.: Objective: To evaluate temporal trends in asthma mortality rates and place of death ...

    Abstract Background: Asthma mortality rates in the United States have declined since 1999; however, asthma mortality by place of death has not been comprehensively evaluated.
    Objective: To evaluate temporal trends in asthma mortality rates and place of death in the United States.
    Methods: We conducted a population-based analysis using data from the Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research platform to evaluate deaths with asthma as the underlying cause (2000-2019) among US residents of all ages. Absolute numbers of asthma-related deaths were described by place of death. Counts were applied to US Census Bureau population counts to calculate mortality rates per 100,000 persons.
    Results: In the 20-year period evaluated, 67,695 asthma deaths were registered in the United States. An overall 32% decline in the asthma mortality rate was observed, from 1.43 to 0.98 per 100,000 persons from 2000 to 2019, respectively. Although asthma mortality rates declined in all medical facility locations, the at-home asthma mortality rate remained stable (0.32 and 0.34 per 100,000 persons in 2000 and 2019, respectively). Consequently, the proportion of at-home asthma deaths increased from 23% in 2000 to 2001 to 36% in 2018 to 2019. The distribution of place of death varied by age, sex, race, ethnicity, and geographic region.
    Conclusion: Despite an overall decline in asthma mortality in the United States, at-home asthma mortality has remained unchanged. In recent years, more than one-third of asthma deaths have occurred at home. These findings warrant further study and underscore the importance of increased efforts to identify and treat uncontrolled asthma across demographic groups.
    MeSH term(s) Humans ; United States/epidemiology ; Death Certificates ; Ethnicity ; Asthma/epidemiology ; Health Facilities ; Mortality
    Language English
    Publishing date 2023-10-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1228189-x
    ISSN 1534-4436 ; 0003-4738 ; 1081-1206
    ISSN (online) 1534-4436
    ISSN 0003-4738 ; 1081-1206
    DOI 10.1016/j.anai.2023.10.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Impact of the COVID-19 Pandemic on Incidence of Asthma Exacerbations and Hospitalizations in US Subspecialist-Treated Patients with Severe Asthma: Results from the CHRONICLE Study.

    Moore, Wendy C / Ledford, Dennis K / Carstens, Donna D / Ambrose, Christopher S

    Journal of asthma and allergy

    2022  Volume 15, Page(s) 1195–1203

    Abstract: Purpose: Patients with severe asthma (SA) are at an increased risk of asthma-related hospitalizations and exacerbations. Despite concerns that COVID-19 circulation would increase exacerbations of SA, anecdotal reports suggest that social distancing and ... ...

    Abstract Purpose: Patients with severe asthma (SA) are at an increased risk of asthma-related hospitalizations and exacerbations. Despite concerns that COVID-19 circulation would increase exacerbations of SA, anecdotal reports suggest that social distancing and exposure avoidance may have led to reduced exacerbations.
    Patients and methods: CHRONICLE is an ongoing noninterventional observational study of 3100 subspecialist-treated patients with SA. Eligible adults (≥ 18 years of age) have (1) current use of monoclonal antibody (ie, biologic) therapy for SA, (2) use of maintenance systemic corticosteroids (mSCS) or other systemic immunosuppressants for ≥ 50% of the prior 12 months for SA, or (3) persistently uncontrolled asthma while treated with high-dosage inhaled corticosteroids with additional controllers. For enrolled patients, electronic medical records were reviewed to record all exacerbations and asthma-related hospitalizations. Descriptive analyses were conducted of the monthly incidence of exacerbations, exacerbation-related visits to the emergency department (ED), and asthma hospitalizations from July 2018 through July 2021.
    Results: Exacerbations, exacerbation-related ED visits, and hospitalizations decreased since April 2020. Exacerbations in 2020 were 20% to 52% lower in April through August relative to the same months in 2019. Exacerbations remained lower than the prior year through May 2021. Similar results were observed by United States (US) census region, with an earlier decrease in exacerbation rates in the western US versus other regions. Across all months, exacerbation rates were lower among biologic recipients.
    Conclusion: In a clinical cohort of subspecialist-treated patients with SA, there was a meaningful reduction in exacerbations, exacerbation-related ED visits, and asthma hospitalizations following COVID-19-related stay-at-home orders and social distancing recommendations. Reasons for these reductions are likely multifactorial, including reduced viral infections due to less social contact and altered patient behavior.
    Language English
    Publishing date 2022-08-31
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2494877-9
    ISSN 1178-6965
    ISSN 1178-6965
    DOI 10.2147/JAA.S363217
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Efficacy of Biologics in Severe, Uncontrolled Asthma Stratified by Blood Eosinophil Count: A Systematic Review.

    Korn, Stephanie / Cook, Bill / Simpson, Lisa J / Llanos, Jean-Pierre / Ambrose, Christopher S

    Advances in therapy

    2023  Volume 40, Issue 7, Page(s) 2944–2964

    Abstract: Introduction: Randomized controlled trials (RCTs) of biologics in patients with severe, uncontrolled asthma have shown differential results by baseline blood eosinophil count (BEC). In the absence of head-to-head trials, we describe the effects of ... ...

    Abstract Introduction: Randomized controlled trials (RCTs) of biologics in patients with severe, uncontrolled asthma have shown differential results by baseline blood eosinophil count (BEC). In the absence of head-to-head trials, we describe the effects of biologics on annualized asthma exacerbation rate (AAER) by baseline BEC in placebo-controlled RCTs. Exacerbations associated with hospitalization or an emergency room visit, pre-bronchodilator forced expiratory volume in 1 s, Asthma Control Questionnaire score, and Asthma Quality of Life Questionnaire score were also summarized.
    Methods: MEDLINE (via PubMed) was searched for RCTs of biologics in patients with severe, uncontrolled asthma and with AAER reduction as a primary or secondary endpoint. AAER ratios and change from baseline in other outcomes versus placebo were compared across baseline BEC subgroups. Analysis was limited to US Food and Drug Administration-approved biologics.
    Results: In patients with baseline BEC ≥ 300 cells/μL, AAER reduction was demonstrated with all biologics, and other outcomes were generally improved. In patients with BEC 0 to < 300 cells/μL, consistent AAER reduction was demonstrated only with tezepelumab; improvements in other outcomes were inconsistent across biologics. In patients with BEC 150 to < 300 cells/μL, consistent AAER reduction was demonstrated with tezepelumab and dupilumab (300 mg dose only), and in those with BEC 0 to < 150 cells/μL, AAER reduction was demonstrated only with tezepelumab.
    Conclusion: The efficacy of all biologics in reducing AAER in patients with severe asthma increases with higher baseline BEC, with varying profiles across individual biologics likely due to differing mechanisms of action.
    MeSH term(s) Humans ; Eosinophils ; Anti-Asthmatic Agents/therapeutic use ; Biological Products/therapeutic use ; Asthma/drug therapy ; Leukocyte Count ; Eosinophilia/drug therapy ; Double-Blind Method
    Chemical Substances Anti-Asthmatic Agents ; Biological Products
    Language English
    Publishing date 2023-05-26
    Publishing country United States
    Document type Systematic Review ; Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 632651-1
    ISSN 1865-8652 ; 0741-238X
    ISSN (online) 1865-8652
    ISSN 0741-238X
    DOI 10.1007/s12325-023-02514-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Efficacy of Biologics in Patients with Allergic Severe Asthma, Overall and by Blood Eosinophil Count: A Literature Review.

    Bernstein, Jonathan A / Llanos, Jean-Pierre / Hunter, Gillian / Martin, Neil / Ambrose, Christopher S

    Advances in therapy

    2023  Volume 40, Issue 11, Page(s) 4721–4740

    Abstract: Patients with uncontrolled, allergic severe asthma may be prescribed biologic therapies to reduce exacerbations and improve disease control. Randomized controlled trials (RCTs) of these therapies have differed in design, with varying results overall and ... ...

    Abstract Patients with uncontrolled, allergic severe asthma may be prescribed biologic therapies to reduce exacerbations and improve disease control. Randomized controlled trials (RCTs) of these therapies have differed in design, with varying results overall and by baseline blood eosinophil count (BEC). This study describes published annualized asthma exacerbation rate (AAER) reductions from RCTs in patients with allergic severe asthma, overall and by baseline BEC category. A literature search was performed to identify published phase 3 RCT data of US Food and Drug Administration-approved biologics for severe asthma in patients with severe, uncontrolled asthma and confirmed sensitization to perennial aeroallergens. Analyses focused on AAER reduction versus placebo in the overall population and/or in those with an elevated or low BEC at baseline or screening. Baseline serum total immunoglobulin E levels varied between RCT populations. In patients with allergic severe asthma across all BEC categories, data were available for tezepelumab, dupilumab, benralizumab and omalizumab only; the greatest AAER reduction was observed with tezepelumab. In patients with allergic severe asthma and BECs of ≥ 260 cells/µL or ≥ 300 cells/μL, AAER reductions were observed with all biologics (tezepelumab, dupilumab, mepolizumab, benralizumab and omalizumab); the greatest AAER reduction was observed with tezepelumab and the smallest AAER reduction was observed with omalizumab. In patients with allergic severe asthma and BECs of < 260 cells/µL or < 300 cells/μL (regardless of historical BEC), an AAER reduction was observed with tezepelumab but not with benralizumab or omalizumab. Differential mechanisms of action may explain the differences in results observed between biologics. Among patients with allergic severe asthma, the efficacy of biologics in RCTs varied considerably overall and by BEC. Tezepelumab was the only biologic to demonstrate AAER reductions consistently across all subgroups. These differences can inform provider treatment decisions when selecting biologic treatments for patients with allergic severe asthma.
    MeSH term(s) Humans ; Eosinophils ; Omalizumab/therapeutic use ; Anti-Asthmatic Agents/therapeutic use ; Asthma/diagnosis ; Biological Products/therapeutic use
    Chemical Substances Omalizumab (2P471X1Z11) ; Anti-Asthmatic Agents ; Biological Products
    Language English
    Publishing date 2023-09-12
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 632651-1
    ISSN 1865-8652 ; 0741-238X
    ISSN (online) 1865-8652
    ISSN 0741-238X
    DOI 10.1007/s12325-023-02647-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Severe RSV disease in preterm infants born at 29 to 35 weeks' gestation in the United States.

    Ambrose, Christopher S

    Pediatrics

    2014  Volume 134, Issue 6, Page(s) e1781

    MeSH term(s) Antibodies, Monoclonal, Humanized/therapeutic use ; Antiviral Agents/therapeutic use ; Humans ; Respiratory Syncytial Virus Infections/prevention & control
    Chemical Substances Antibodies, Monoclonal, Humanized ; Antiviral Agents
    Language English
    Publishing date 2014-12
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 207677-9
    ISSN 1098-4275 ; 0031-4005
    ISSN (online) 1098-4275
    ISSN 0031-4005
    DOI 10.1542/peds.2014-2901A
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Response to Morimoto and Takeishi 2018.

    Mallory, Raburn M / Ambrose, Christopher S

    Vaccine

    2018  Volume 37, Issue 35, Page(s) 4852

    MeSH term(s) Heat-Shock Proteins ; Humans ; Influenza, Human ; Vaccination
    Chemical Substances Heat-Shock Proteins
    Language English
    Publishing date 2018-10-03
    Publishing country Netherlands
    Document type Letter ; Comment
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2018.09.066
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Safety of live attenuated influenza vaccine (LAIV) in children and adults with asthma: a systematic literature review and narrative synthesis.

    Bandell, Allyn / Ambrose, Christopher S / Maniaci, Jon / Wojtczak, Henry

    Expert review of vaccines

    2021  Volume 20, Issue 6, Page(s) 717–728

    Abstract: Introduction: Asthma is one of the most common chronic respiratory conditions worldwide and can be exacerbated by influenza. Findings from early trials demonstrated a higher risk of medically significant wheezing in otherwise healthy young children ( ... ...

    Abstract Introduction: Asthma is one of the most common chronic respiratory conditions worldwide and can be exacerbated by influenza. Findings from early trials demonstrated a higher risk of medically significant wheezing in otherwise healthy young children (aged 6 - 23 months) following administration of the Ann Arbor-backbone live attenuated influenza vaccine (LAIV-AA). In more recent years, several additional studies have investigated the safety of LAIV-AA in older children (2 - 17 years of age) and adults with asthma or prior wheezing, but these findings have not yet been systematically evaluated.
    Areas covered: We conducted a systematic literature review to assess and synthesize the evidence from all available studies on the safety of LAIV-AA in people aged 2 - 49 years with a diagnosis of asthma or recurrent wheezing.
    Expert opinion: Fourteen studies over 20 years, involving a total of 1.2 million participants, provided evidence that LAIV-AA was well tolerated with no safety concerns in individuals aged 2 - 49 years with a diagnosis of asthma or recurrent wheezing. These data can help inform guidelines for use of LAIV-AA in children and adults with a history of asthma or recurrent wheezing.
    MeSH term(s) Adolescent ; Adult ; Asthma/chemically induced ; Child ; Child, Preschool ; Humans ; Infant ; Influenza Vaccines ; Influenza, Human/prevention & control ; Middle Aged ; Respiratory Sounds ; Vaccines, Attenuated ; Young Adult
    Chemical Substances Influenza Vaccines ; Vaccines, Attenuated
    Language English
    Publishing date 2021-06-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
    ZDB-ID 2181284-6
    ISSN 1744-8395 ; 1476-0584
    ISSN (online) 1744-8395
    ISSN 1476-0584
    DOI 10.1080/14760584.2021.1925113
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