International Severe Asthma Registry (ISAR): 2017-2024 Status and Progress Update.Tuberculosis and respiratory diseases • December 23, 2024
Mohsen Sadatsafavi, Trung Tran, Ghislaine Scelo, Ming-ju Tsai, John Busby, Benjamin Emmanuel, Liam Heaney, Christine Jenkins, Flavia Hoyte, Giorgio Canonica, Rohit Katial, Enrico Heffler, Eileen Wang, Francesca Puggioni, Michael Wechsler, Ledit R Ardusso, Jorge Máspero, Martin Sivori, Cathy Emmas, Andrew Menzies Gow, Neda Stjepanovic, Sinthia Bosnic Anticevich, Belinda Cochrane, Eve Denton, Peter Gibson, Mark Hew, Peter Middleton, Matthew Peters, Guy Brusselle, Renaud Louis, Florence Schleich, George Christoff, Todor Popov, Celine Bergeron, Mohit Bhutani, Kenneth Chapman, Andréanne Côté, Simon Couillard, Delbert Dorscheid, Libardo Jiménez Maldonado, Ivan Solarte, Carlos Torres Duque, Susanne Hansen, Celeste Porsbjerg, Charlotte Ulrik, Alan Altraja, Arnaud Bourdin, Konstantinos Exarchos, Athena Gogali, Konstantinos Kostikas, Michael Makris, Andriana Papaioannou, Patrick Mitchell, Takashi Iwanaga, Tatsuya Nagano, Yuji Tohda, Mona Al Ahmad, Désirée Larenas Linnemann, Bernt Aarli, Piotr Kuna, Cláudia Chaves Loureiro, Riyad Al Lehebi, Adeeb Bulkhi, Wenjia Chen, Yah Juang, Mariko Koh, Anqi Liu, Chin Rhee, Borja Cosio, Luis Perez De Llano, Diahn-warng Perng, Chau-chyun Sheu, Hao-chien Wang, Bassam Mahboub, Laila Salameh, David Jackson, Pujan Patel, Paul Pfeffer, Njira Lugogo, Roy Pleasants, Aaron Beastall, Lakmini Bulathsinhala, Victoria Carter, Nevaashni Eleangovan, Kirsty Fletton, John Townend, Ruth Murray, David Price
Rationale: Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes.
Objective: To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators.
Methods: This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. Measurements and Main
Results: A total of 42,908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake ⩾90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; P = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; P = 0.006), major cardiovascular events (0.65 [0.44-0.97]; P = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; P = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets.
Conclusions: Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.
Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics.American Journal Of Respiratory And Critical Care Medicine • May 18, 2025
Mohsen Sadatsafavi, Trung Tran, Ghislaine Scelo, Ming-ju Tsai, John Busby, Benjamin Emmanuel, Liam Heaney, Christine Jenkins, Flavia Hoyte, Giorgio Canonica, Rohit Katial, Enrico Heffler, Eileen Wang, Francesca Puggioni, Michael Wechsler, Ledit R Ardusso, Jorge Máspero, Martin Sivori, Cathy Emmas, Andrew Menzies Gow, Neda Stjepanovic, Sinthia Bosnic Anticevich, Belinda Cochrane, Eve Denton, Peter Gibson, Mark Hew, Peter Middleton, Matthew Peters, Guy Brusselle, Renaud Louis, Florence Schleich, George Christoff, Todor Popov, Celine Bergeron, Mohit Bhutani, Kenneth Chapman, Andréanne Côté, Simon Couillard, Delbert Dorscheid, Libardo Jiménez Maldonado, Ivan Solarte, Carlos Torres Duque, Susanne Hansen, Celeste Porsbjerg, Charlotte Ulrik, Alan Altraja, Arnaud Bourdin, Konstantinos Exarchos, Athena Gogali, Konstantinos Kostikas, Michael Makris, Andriana Papaioannou, Patrick Mitchell, Takashi Iwanaga, Tatsuya Nagano, Yuji Tohda, Mona Al Ahmad, Désirée Larenas Linnemann, Bernt Aarli, Piotr Kuna, Cláudia Chaves Loureiro, Riyad Al Lehebi, Adeeb Bulkhi, Wenjia Chen, Yah Juang, Mariko Koh, Anqi Liu, Chin Rhee, Borja Cosio, Luis Perez De Llano, Diahn-warng Perng, Chau-chyun Sheu, Hao-chien Wang, Bassam Mahboub, Laila Salameh, David Jackson, Pujan Patel, Paul Pfeffer, Njira Lugogo, Roy Pleasants, Aaron Beastall, Lakmini Bulathsinhala, Victoria Carter, Nevaashni Eleangovan, Kirsty Fletton, John Townend, Ruth Murray, David Price
Rationale: Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes.
Objective: To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators.
Methods: This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. Measurements and Main
Results: A total of 42,908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake ⩾90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; P = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; P = 0.006), major cardiovascular events (0.65 [0.44-0.97]; P = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; P = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets.
Conclusions: Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.
Impact of clinical remission on quality of life in severe eosinophilic asthma treated with mepolizumab.Annals Of Allergy, Asthma & Immunology : Official Publication Of The American College Of Allergy, Asthma, & Immunology • April 10, 2025
Janet Bondarenko, Angela Burge, Jean Bremner, Elizabeth Webb, Atsuhito Nakazawa, Simone Corso, VĂ©ronique Pepin, Brenda Button, Mark Hew, Anne Holland
Background: Dysfunctional breathing is common and leads to worse asthma outcomes.
Objective: To describe the characteristics of nonpharmacological interventions to treat dysfunctional breathing, and evidence for their efficacy.
Methods: We searched electronic databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, and Physiotherapy Evidence Database) to identify studies that involved nonpharmacological interventions for people with the diagnosis of dysfunctional breathing. The primary aim was to determine the characteristics of intervention protocols according to the Template for Intervention Description and Replication checklist. Secondary aims included the assessment tools used, outcomes measured, and the clinical impact of the intervention. We assessed the risk of bias using the Cochrane Risk of Bias 1.0 tool or the Standard Quality Assessment Criteria, depending on the study design.
Results: A total of 68 trials met review criteria (26 cohort studies, 20 case series, 19 randomized trials, and three nonrandomized trials), with 2,119 participants. Most studies had a high or unclear risk of bias across multiple domains. Five groups of nonpharmacological interventions were identified: breathing retraining with or without biofeedback, psychological therapy, acupoint therapy, manual therapy, and exercise therapy. Intervention components were highly variable and inadequately reported. Breathing retraining was the most reported intervention and showed positive effects across biochemical (29 of 34 studies; 85%), biomechanical (10 of 10 studies; 100%), and psychophysiological (15 of 19; 79%) domains of dysfunctional breathing. There was marked heterogeneity across studies and outcomes.
Conclusions: A variety of nonpharmacological interventions have been applied in people with dysfunctional breathing. Breathing retraining was frequently studied, with low-quality evidence for efficacy. Future studies should report intervention components in sufficient detail to allow replication and use consistent objective measurements to assess outcomes.
Non-Pharmacological interventions for dysfunctional breathing in adults: a systematic review.The Journal Of Allergy And Clinical Immunology. In Practice • March 01, 2025
Janet Bondarenko Bpt, Angela Burge, Jean Bremner Bpt, Elizabeth Webb Bpt, Atsuhito Nakazawa, Simone Corso, VĂ©ronique Pepin, Brenda Button, Mark Hew, Anne Holland
Background: Dysfunctional breathing is common and leads to worse asthma outcomes.
Objective: To describe the characteristics of non-pharmacological interventions to treat dysfunctional breathing, and evidence for their efficacy.
Methods: Electronic databases (MEDLINE, Embase, CINAHL, CENTRAL and PEDro) were searched to identify studies that involved non-pharmacological interventions for people diagnosed with dysfunctional breathing. The primary aim was to determine the characteristics of intervention protocols according to the Template for Intervention Description and Replication checklist. Secondary aims included the assessment tools used, outcomes measured, and the clinical impact of the intervention. Risk of bias was assessed using the Cochrane Risk of Bias 1.0 tool or the Standard Quality Assessment Criteria depending on study design.
Results: Sixty-eight trials met review criteria (26 cohort studies, 20 case series, 19 randomised trials, and 3 non-randomised trials) with a total of 2119 participants. Most studies had high or unclear risk of bias across multiple domains. Five groups of non-pharmacological interventions were identified: breathing re-training ± biofeedback, psychological therapy, acupoint therapy, manual therapy, and exercise therapy. Intervention components were highly variable and inadequately reported. Breathing re-training was the most reported intervention and showed positive effects across biochemical (29/34 studies, 85%), biomechanical (10/10 studies, 100%) and psychophysiological (15/19, 79%) domains of dysfunctional breathing. There was marked heterogeneity across studies and outcomes.
Conclusions: A variety of non-pharmacological interventions have been applied in people with dysfunctional breathing. Breathing re-training was frequently studied with low quality evidence for efficacy. Future studies should report intervention components in sufficient detail to allow replication and use consistent objective measurements to assess outcomes.
Impact of Biologics Initiation on Oral Corticosteroid Use in the International Severe Asthma Registry and the Optimum Patient Care Research Database: A Pooled Analysis of Real-World Data.The Journal Of Allergy And Clinical Immunology. In Practice • December 25, 2024
Wenjia Chen, Trung Tran, John Townend, George Christoff, Ming-ju Tsai, Alan Altraja, Belinda Cochrane, Borja Cosio, Martin Sivori, Ruth Murray, Michael Makris, Ghislaine Scelo, Lakmini Bulathsinhala, Ledit R Ardusso, MarĂa Franchi, Jorge Máspero, Fernando Saldarini, Ana Stok, Ana Tomaszuk, AnahĂ Yañez, Benjamin Emmanuel, Cathy Emmas, Konstantinos Kostikas, Andrew Menzies Gow, Neda Stjepanovic, Sinthia Bosnic Anticevich, Eve Denton, Peter Gibson, Mark Hew, Christine Jenkins, Peter Middleton, Matthew Peters, John Upham, Guy Brusselle, Renaud Louis, Florence Schleich, Paulo Pitrez, Todor Popov, Celine Bergeron, Mohit Bhutani, Kenneth Chapman, AndrĂ©anne CĂ´tĂ©, Simon Couillard, Delbert Dorscheid, M Lougheed, Mohsen Sadatsafavi, Carlos Celis Preciado, Libardo JimĂ©nez Maldonado, Bellanid RodrĂguez Cáceres, Diana Cano Rosales, Ivan Solarte, Carlos Torres Duque, Susanne Hansen, Celeste Porsbjerg, Charlotte Ulrik, Arnaud Bourdin, Petros Bakakos, Konstantinos Exarchos, Athena Gogali, Aggelos Ladias, Nikolaos Papadopoulos, Andriana Papaioannou, Richard Costello, Breda Cushen, Patrick Mitchell, Giorgio Canonica, Enrico Heffler, Francesca Puggioni, Takashi Iwanaga, Tatsuya Nagano, Yuji Tohda, Mona Al Ahmad, DĂ©sirĂ©e Larenas Linnemann, Bernt Aarli, Sverre Lehmann, Piotr Kuna, JosĂ© Ferreira, JoĂŁo Fonseca, Cláudia Loureiro, Riyad Al Lehebi, Adeeb Bulkhi, Yah Juang, Mariko Koh, Anqi Liu, Chin Rhee, Luis Perez De Llano, Pin-kuei Fu, Diahn-warng Perng, Chau-chyun Sheu, Hao-chien Wang, Bassam Mahboub, Laila Salameh, John Busby, Liam Heaney, David Jackson, Pujan Patel, Paul Pfeffer, Flavia Hoyte, Rohit Katial, Njira Lugogo, Roy Pleasants, Eileen Wang, Michael Wechsler, Aaron Beastall, Victoria Carter, Nevaashni Eleangovan, Kirsty Fletton, David Price
Background: For severe asthma (SA) management, real-world evidence on the effects of biologic therapies in reducing the burden of oral corticosteroid (OCS) use is limited.
Objective: To estimate the efficacy of biologic initiation on total OCS (TOCS) exposure in patients with SA from real-world specialist and primary care settings.
Methods: From the International Severe Asthma Registry (ISAR, specialist care) and the Optimum Patient Care Research Database (OPCRD, primary care, United Kingdom), adult biologic initiators were identified and propensity score-matched with non-initiators (ISAR, 1:1; OPCRD, 1:2). The impact of biologic initiation on TOCS (including bursts for exacerbations) daily dose in the first- and second-year follow-up period was estimated using multivariable generalized linear models.
Results: Among 5,663 patients (ISAR 48%, OPCRD 52%), the odds ratios (ORs) of biologic initiators achieving TOCS cessation in the first and second years of follow-up were 2.38 (95% CI, 1.87-3.04) and 2.11 (95% CI, 1.65-2.70), whereas the ORs of low (0- to 5-mg) TOCS intake were 1.62 (95% CI, 1.40-1.86) and 1.40 (95% CI, 1.21-1.61), respectively. Compared with non-initiators, biologic initiators had a substantially higher chance of achieving greater than 75% reduction from baseline (OR [95% CI] = 2.35 [2.06-2.68] and 1.53 [1.35-1.73] in first and second years, respectively). These findings remained persistent and robust when analyses were repeated with one country setting removed at a time.
Conclusions: Biologic initiation in patients with SA led to substantial reduction in TOCS exposure, particularly in the first year. Future analyses will explore the impact on OCS-related adverse health events.
