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  1. Article ; Online: Long-Term Effectiveness of Anti-IL4R Therapy Following Suboptimal Response to Anti-IL5/5R Therapy in Severe Eosinophilic Asthma.

    Gates, Jessica / Hearn, Andrew / Mason, Tom / Fernandes, Mariana / Green, Linda / Thomson, Louise / Roxas, Cris / Lam, Jodie / d'Ancona, Grainne / Nanzer, Alexandra M / Dhariwal, Jaideep / Jackson, David J

    The journal of allergy and clinical immunology. In practice

    2024  

    Abstract: Background: Dupilumab is an anti-IL4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). A suboptimal response to anti-IL5/5R mAbs is seen in some patients with ongoing evidence of T2 inflammation.: Objective: To ... ...

    Abstract Background: Dupilumab is an anti-IL4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). A suboptimal response to anti-IL5/5R mAbs is seen in some patients with ongoing evidence of T2 inflammation.
    Objective: To understand whether targeting IL-13 pathways with dupilumab in these patients may lead to better clinical outcomes.
    Methods: We performed a retrospective analysis of the extended clinical effectiveness of dupilumab up to 2 years of treatment in patients with SEA who had not responded adequately to anti-IL5/5R biologics. Ability to achieve clinical remission and change in the remission domains of exacerbation rate (AER), maintenance oral corticosteroid dose (mOCS), lung function (FEV1) and asthma control (ACQ6) were recorded.
    Results: Thirty-seven patients (mean age 41, 70% female) were included in the analysis. The mean (SD) AER fell by almost 90% from 3.16(1.28) at dupilumab initiation to 0.35(0.72) after 1 year. The median (IQR) mOCS dose (n=20) fell from 10(5-25) mg to 0 (0-5) mg at 1 year, with 14/20 (70%) able to stop prednisolone altogether. Clinical remission was achieved in 16/37 (43%). Patients who achieved remission had a higher pre-IL5/5R FeNO level (85ppb [39-198] vs 75ppb [42-96], p=0.03).
    Conclusion: Significant improvements in clinical outcomes are possible following a switch to dupilumab in patients experiencing a suboptimal response to anti-IL5/5R therapies. A higher FeNO in poor responders to anti-IL5/5R who achieve remission with dupilumab is suggestive of an IL-13 driven sub-phenotype of T2-high asthma in which the eosinophil appears unlikely to play a key role in the disease pathogenesis.
    Language English
    Publishing date 2024-04-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2843237-X
    ISSN 2213-2201 ; 2213-2198
    ISSN (online) 2213-2201
    ISSN 2213-2198
    DOI 10.1016/j.jaip.2024.03.049
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 7086: Show issues Location:
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  2. Article ; Online: The impact of steroid-sparing biologic therapies on weight loss in obese individuals with severe eosinophilic asthma.

    Nanzer, Alexandra M / Taylor, Victoria / Hearn, Andrew P / Kavanagh, Joanne E / Patrick, Tanya / Green, Linda / Thomson, Louise / Lam, Jodie / Fernandes, Mariana / Roxas, Cris / d'Ancona, Grainne / Kent, Brian D / Dhariwal, Jaideep / Jackson, David J

    The European respiratory journal

    2023  Volume 62, Issue 2

    MeSH term(s) Humans ; Asthma/complications ; Asthma/drug therapy ; Biological Therapy ; Steroids ; Obesity/complications ; Weight Loss
    Chemical Substances Steroids
    Language English
    Publishing date 2023-08-03
    Publishing country England
    Document type Letter
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/13993003.00245-2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2322: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 292: Show issues

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  3. Article ; Online: Nocturnal Hypoxemia Associates With Symptom Progression and Mortality in Patients With Progressive Fibrotic Interstitial Lung Disease.

    Myall, Katherine J / West, Alex G / Martinovic, Jennifer L / Lam, Jodie L / Roque, Diana / Wu, Zhe / Maher, Toby M / Molyneaux, Philip L / Suh, Eui-Sik / Kent, Brian D

    Chest

    2023  Volume 164, Issue 5, Page(s) 1232–1242

    Abstract: Background: OSA and nocturnal hypoxemia (NH) are common in patients with fibrotic interstitial lung disease (F-ILD), but their relationship with disease outcomes remains unclear.: Research question: What is the relationship between NH and OSA and ... ...

    Abstract Background: OSA and nocturnal hypoxemia (NH) are common in patients with fibrotic interstitial lung disease (F-ILD), but their relationship with disease outcomes remains unclear.
    Research question: What is the relationship between NH and OSA and clinical outcomes in patients with F-ILD?
    Study design and methods: This was a prospective observational cohort study of patients with F-ILD and without daytime hypoxemia. Patients underwent home sleep study at baseline and were followed up for at least 1 year or until death. NH was defined as ≥ 10% of sleep with oxygen saturation of < 90%. OSA was defined as an apnea-hypopnea index of ≥ 15 events/h.
    Results: Among 102 participants (male, 74.5%; age, 73.0 ± 8.7 years; FVC, 2.74 ± 0.78 L; 91.1% idiopathic pulmonary fibrosis), 20 patients (19.6%) demonstrated prolonged NH and 32 patients (31.4%) showed OSA. No significant differences were found between those with and without NH or OSA at baseline. Despite this, NH was associated with a more rapid decline in both quality of life as measured by the King's Brief Interstitial Lung Disease questionnaire (change, -11.3 ± 5.3 points in the NH group vs -6.7 ± 6.5 in those without NH; P = .005) and higher all-cause mortality at 1 year (hazard ratio, 8.21; 95% CI, 2.40-28.1; P < .001). No statistically significant difference was seen between the groups in annualized change in measures of pulmonary function testing.
    Interpretation: Prolonged NH, but not OSA, is associated with worsening disease-related quality of life and increased mortality in patients with F-ILD.
    MeSH term(s) Aged ; Aged, 80 and over ; Humans ; Male ; Middle Aged ; Disease Progression ; Hypoxia/complications ; Lung Diseases, Interstitial/diagnosis ; Prospective Studies ; Quality of Life ; Sleep Apnea, Obstructive/complications ; Female
    Language English
    Publishing date 2023-05-13
    Publishing country United States
    Document type Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 1032552-9
    ISSN 1931-3543 ; 0012-3692
    ISSN (online) 1931-3543
    ISSN 0012-3692
    DOI 10.1016/j.chest.2023.05.013
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    Ui III Zs.45: Show issues Location:
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    Zs.MO 349: Show issues

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  4. Article ; Online: Identifying patients at risk of post-discharge complications related to COVID-19 infection.

    Hall, Jocelin / Myall, Katherine / Lam, Jodie L / Mason, Thomas / Mukherjee, Bhashkar / West, Alex / Dewar, Amy

    Thorax

    2021  Volume 76, Issue 4, Page(s) 408–411

    Abstract: SARS-CoV-2 infection is a multisystem disease with post-discharge sequelae. We report early follow-up data from one UK hospital of the initial 200 hospital inpatients with slow recovery from the condition. At 4 weeks post-discharge, 321/957 survivors (34% ...

    Abstract SARS-CoV-2 infection is a multisystem disease with post-discharge sequelae. We report early follow-up data from one UK hospital of the initial 200 hospital inpatients with slow recovery from the condition. At 4 weeks post-discharge, 321/957 survivors (34%) had persistent symptoms. A structured outpatient clinical assessment protocol was designed, and outcomes from the first 200 patients seen 4-6 weeks post-discharge are presented here. In 80/200 (40%), we identified at follow-up a cardiorespiratory cause of breathlessness, including persistent parenchymal abnormality (64 patients), pulmonary embolism (four patients) and cardiac complications (eight patients). These findings occurred both in patients who had intensive care unit (ICU) admissions and those who had been managed on the ward, although patients requiring ICU admissions were more likely to have a significant cardiorespiratory cause found for their breathlessness, risk ratio 2.8 (95% CI 1.5 to 5.1).
    MeSH term(s) Aftercare/methods ; COVID-19/diagnosis ; COVID-19/epidemiology ; Critical Care ; Female ; Follow-Up Studies ; Humans ; Intensive Care Units/statistics & numerical data ; Male ; Middle Aged ; Pandemics ; Patient Discharge/statistics & numerical data ; Retrospective Studies ; Risk Assessment/methods ; SARS-CoV-2
    Language English
    Publishing date 2021-02-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 204353-1
    ISSN 1468-3296 ; 0040-6376
    ISSN (online) 1468-3296
    ISSN 0040-6376
    DOI 10.1136/thoraxjnl-2020-215861
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Ui III Zs.83: Show issues Location:
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  5. Article ; Online: Long-Term Effectiveness of Benralizumab in Eosinophilic Granulomatosis With Polyangiitis.

    Nanzer, Alexandra M / Maynard-Paquette, Anne-Catherine / Alam, Vardah / Green, Linda / Thomson, Louise / Lam, Jodie / Fernandes, Mariana / Roxas, Cris / d'Ancona, Grainne / Hearn, Andrew / Gates, Jessica / Agarwal, Sangita / Kent, Brian D / Fernando, Michelle / D'Cruz, David P / Hopkins, Claire / Ismail, Tevfik F / Dhariwal, Jaideep / Jackson, David J

    The journal of allergy and clinical immunology. In practice

    2024  Volume 12, Issue 3, Page(s) 724–732

    Abstract: Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease characterized by eosinophilic tissue inflammation. Benralizumab, an anti-IL-5 receptor (anti-IL-5R) monoclonal antibody, induces rapid depletion of eosinophils; ... ...

    Abstract Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease characterized by eosinophilic tissue inflammation. Benralizumab, an anti-IL-5 receptor (anti-IL-5R) monoclonal antibody, induces rapid depletion of eosinophils; its longer-term effect in EGPA is unknown.
    Objective: To assess the real-world effectiveness and clinical remission rates of anti-IL-5R therapy in EGPA.
    Methods: We performed a retrospective cohort analysis of patients with EGPA, who commenced treatment with benralizumab. Clinical remission, assessed at 1 year and 2 years after the initiation of benralizumab, was defined as an absence of active vasculitis (Birmingham Vasculitis Activity Score of 0) and an oral corticosteroid (OCS) dose of ≤4 mg/d of prednisolone. "Super-responders" were defined as patients in remission and free of any significant relapses (asthma or extrapulmonary) over the preceding 12 months. The corticosteroid-sparing capacity of benralizumab, patient-reported outcome measures, and characteristics associated with clinical remission and super-responder status were also analyzed.
    Results: A total of 70 patients completed at least 1 year of treatment with benralizumab, of whom 53 completed 2 years. Of 70 patients, 47 (67.1%) met the definition for clinical remission at 1 year, with a similar proportion in remission at 2 years. Excluding asthma-related relapses, 61 of 70 (87.1%) patients were relapse free at 1 year, and of the 53 who completed 2 years, 45 (84.9%) were relapse free. A total of 67.9% of patients no longer needed any OCS for disease control. No significant difference was seen between antineutrophilic cytoplasmic antibody (ANCA)-positive and ANCA-negative subgroups.
    Conclusions: In this real-world setting of patients with EGPA, treatment with benralizumab was well tolerated and resulted in corticosteroid-free clinical remission for the majority of patients.
    MeSH term(s) Humans ; Churg-Strauss Syndrome/drug therapy ; Granulomatosis with Polyangiitis/drug therapy ; Antibodies, Antineutrophil Cytoplasmic ; Retrospective Studies ; Asthma/drug therapy ; Adrenal Cortex Hormones/therapeutic use ; Eosinophilia ; Recurrence ; Antibodies, Monoclonal, Humanized
    Chemical Substances benralizumab (71492GE1FX) ; Antibodies, Antineutrophil Cytoplasmic ; Adrenal Cortex Hormones ; Antibodies, Monoclonal, Humanized
    Language English
    Publishing date 2024-01-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2843237-X
    ISSN 2213-2201 ; 2213-2198
    ISSN (online) 2213-2201
    ISSN 2213-2198
    DOI 10.1016/j.jaip.2024.01.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 7086: Show issues Location:
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  6. Article ; Online: Persistent Post-COVID-19 Interstitial Lung Disease. An Observational Study of Corticosteroid Treatment.

    Myall, Katherine Jane / Mukherjee, Bhashkar / Castanheira, Ana Margarida / Lam, Jodie L / Benedetti, Giulia / Mak, Sze Mun / Preston, Rebecca / Thillai, Muhunthan / Dewar, Amy / Molyneaux, Philip L / West, Alex G

    Annals of the American Thoracic Society

    2021  Volume 18, Issue 5, Page(s) 799–806

    Abstract: Rationale: ...

    Abstract Rationale:
    MeSH term(s) Aftercare/methods ; COVID-19/complications ; COVID-19/mortality ; COVID-19/therapy ; Female ; Glucocorticoids/therapeutic use ; Hospitalization/statistics & numerical data ; Humans ; Lung/diagnostic imaging ; Lung/physiopathology ; Lung/virology ; Lung Diseases, Interstitial/diagnosis ; Lung Diseases, Interstitial/etiology ; Lung Diseases, Interstitial/physiopathology ; Lung Diseases, Interstitial/therapy ; Male ; Middle Aged ; Patient Discharge/statistics & numerical data ; Respiratory Function Tests/methods ; SARS-CoV-2/isolation & purification ; Survivors/statistics & numerical data ; Symptom Assessment/methods ; Symptom Assessment/statistics & numerical data ; Tomography, X-Ray Computed/methods ; Treatment Outcome ; United Kingdom/epidemiology
    Chemical Substances Glucocorticoids
    Language English
    Publishing date 2021-01-12
    Publishing country United States
    Document type Journal Article ; Observational Study
    ZDB-ID 2717461-X
    ISSN 2325-6621 ; 1943-5665 ; 2325-6621
    ISSN (online) 2325-6621 ; 1943-5665
    ISSN 2325-6621
    DOI 10.1513/AnnalsATS.202008-1002OC
    Database MEDical Literature Analysis and Retrieval System OnLINE

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