Peter G. Gibson

BMJ open • March 26, 2025

Elissa Elvidge, Vanessa Murphy, Melanie Rao, Peter Gibson, Karen Mclaughlin, Annelies Robijn, Megan Jensen, Leonie Callaway, John Attia, Michael Hensley, Warwick Giles, Michael Peek, Helen Barrett, Sean Seeho, Joerg Mattes, Alistair Abbott, Andrew Bisits, Kirsten Mccaffery, Paul Colditz, Andrew Searles, Shanthi Ramanathan

Objective: The Breathing for Life Trial (BLT) was a multicentre randomised controlled trial testing the hypothesis that a fractional exhaled nitric oxide-based intervention to guide asthma therapy in pregnancy improves perinatal outcomes. While BLT was negative based on selected outcomes, the conduct of the trial over 7 years showed potential for assessing the broader research impacts and returns on investment in BLT. The aim of this study was to retrospectively assess and report on the impact and value of BLT to show accountability for the research investment in what was deemed a 'negative' trial. Methods: The Framework to Assess the Impact from Translational health research (FAIT) was selected as the preferred method. FAIT combines three validated methods, including a modified Payback framework, an economic analysis of return on investment and a narrative account of the impact generated from the research. Data collection was done via document analysis of BLT administrative and research records and review of relevant websites/databases. Results: BLT delivered a return on investment of $6.7 million in leveraged grants, fellowships and consultancies and conservatively returned $2.44 for every dollar invested. The research trained and upskilled 18 midwives and obstetricians in evidence-based asthma management in pregnancy and improved research capability of six PhD students. Specialised equipment purchased by BLT is now being repurposed to undertake other research in regional Australia, saving further research investment. Of the 1200 mothers who were part of BLT, 508 now have written asthma plans, 268 had a clinically significant improvement in their asthma control score and the proportion who improved their asthma plan knowledge increased by 58 percentage points from 12 to 70%. Conclusions: This case example in the developing field of impact assessment illustrates how researchers can use evidence to demonstrate and report more broadly on the impact of and returns on research investment in a clinical trial.

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

Background: 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 non-initiators. 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; UK). For biologic-initiators, the index date was the date of biologic-initiation. For non-initiators, it was the date of enrolment (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 (HR) of developing OCS-related adverse outcomes for up to five years from the index date. Results: 42,908 patients were included. Overall, 27.3% and 4.7% of biologic-initiators and non-initiators were long-term OCS users (daily intake ≥90 consecutive days in year pre-index), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared to non-initiators, biologic-initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% 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/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 AOs 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.

The Journal Of Allergy And Clinical Immunology. In Practice • February 13, 2025

Dennis Thomas, Yuto Hamada, Peter Gibson, Chris Brightling, Mario Castro, Liam Heaney

Type 2 (T2) low asthma is characterized by the absence of T2-mediated eosinophilic airway inflammation. The diagnosis and prevalence of T2-low asthma are complicated by the absence of specific biomarkers, varied cut-offs of existing biomarkers and biomarker suppression by corticosteroids. The substantial disease burden of T2-low asthma can be attributed to comorbidities, including obesity. T2-low asthma phenotypes include late-onset, aging-related, obesity-related, as well as neutrophilic and paucigranulocytic subtypes. Emerging evidence suggests that T2-low asthma may be more prevalent in mild to moderate asthma compared to severe asthma. Furthermore, the exacerbation phenotype in most patients with severe T2-low asthma may change to T2-high during an exacerbation, while the long-term prognosis in T2-low severe asthma remains unclear. Clinical management strategies for T2-low asthma include addressing comorbidities and risk factors, optimizing inhaled/oral corticosteroid dose, and considering other potential add-on therapies, including azithromycin, anti-thymic stromal lymphopoietin therapy and bronchial thermoplasty. Azithromycin is a promising treatment option, showing potential to induce clinical remission in up to 50% of patients with T2-low uncontrolled asthma and demonstrates the therapeutic potential of targeting microbial dysbiosis in T2-low asthma. Future directions include biologics targeting IL33 pathways, and Glucagon-Like Peptide 1 (GLP-1) and Gastric Inhibitory Polypeptide (GIP) receptor agonists in obesity-related T2-low asthma. Further research is needed to optimize management strategies for T2-low asthma phenotypes.

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, María Franchi, Jorge Máspero, Fernando Saldarini, Ana Stok, Ana Tomaszuk, Anahí 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, Andréanne Côté, Simon Couillard, Delbert Dorscheid, M Lougheed, Mohsen Sadatsafavi, Carlos Celis Preciado, Libardo Jiménez Maldonado, Bellanid Rodríguez 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, Désirée Linnemann, Bernt Aarli, Sverre Lehmann, Piotr Kuna, José Ferreira, João 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 SA patients 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, UK), 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 5663 patients (ISAR 48%, OPCRD 52%), the odds ratios (ORs) of biologic initiators achieving TOCS cessation in the first and second year 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 (0-5mg) TOCS intake were 1.62 (95% CI, 1.40-1.86) and 1.40 (95% CI, 1.21-1.61) respectively. Compared to non-initiators, biologic initiators had a substantially higher chance of achieving >75% reduction from baseline (OR [95% CI]: 2.35 [2.06-2.68] and 1.53 [1.35-1.73] in first and second year, respectively). These findings remained persistent and robust, when analyses were repeated with one country setting removed at a time. Conclusions: Biologic initiation in SA patients led to substantial reduction in TOCS exposure, in particular in the first year. Future analyses will explore the impact on OCS-related adverse health events.

The World Allergy Organization Journal • December 18, 2024

Florence Schleich, Désirée Larenas Linnemann, Alan Altraja, Luis Pérez De Llano, Konstantinos Kostikas, Mohsen Sadatsafavi, Arnaud Bourdin, Roy Alton Pleasants, Mark Hew, Wenjia Chen, Libardo Jiménez Maldonado, Simon Couillard, Charlotte Suppli Ulrik, Adeeb Bulkhi, Ming-ju Tsai, George Christoff, Nikolaos Papadopoulos, Paul Pfeffer, Dermot Ryan, Celine Bergeron, Mona Al Ahmad, Delbert Dorscheid, Eileen Wang, John Blakey, Belinda Cochrane, Matthew Peters, Todor Popov, Carlos Torres Duque, Susanne Hansen, Francesca Puggioni, Kirsty Fletton, Laila Salameh, Peter Middleton, Paulo Márcio Pitrez, Chin Kook Rhee, Eve Denton, Kenneth Chapman, Lauri Lehtimäki, Ruth Murray, Chau-chyun Sheu, David Jackson, Riyad Al Lehebi, Mariko Siyue Koh, Bassam Mahboub, Ledit R Ardusso, Athena Gogali, Giorgio Canonica, Piotr Kuna, Martin Sivori, Renaud Louis, Shelley Abercromby, Giuseppe Guida, Bernt Aarli, Aaron Beastall, Victoria Carter, Ghislaine Scelo, John Townend, Borja Cosio, Pujan Patel, Celine Yun Goh, Zsuzsanna Csoma, John Upham, João Fonseca, Peter Gibson, Christine Jenkins, Guy Brusselle, Anne Chèvremont, Andréanne Côté, Carlos Celis Preciado, Ivan Solarte, Celeste Porsbjerg, Asger Sverrild, Paula Kauppi, Stelios Loukides, Michael Makris, Andriana Papaioannou, Enrico Heffler, Jeffrey Shi Chan, Hyonsoo Joo, Liam Heaney, Wei-han Cheng, Njira Lugogo, Michael Wechsler, Cláudia Chaves Loureiro, Bellanid Rodríguez Cáceres, Tatsuya Nagano, Zhixiao Wang, Hao-chien Wang, Jorge Máspero, Fernando Saldarini, Ana Stok, Anahi Yañez, Philip Bardin, Sinthia Bosnic Anticevich, Vidya Navaratnam, Mohit Bhutani, M Lougheed, Lyle Melenka, Petros Bakakos, Konstantinos Exarchos, Aggelos Ladias, Dóra Lúdvíksdóttir, Takashi Iwanaga, Elvia Contreras, Sverre Lehmann, José Ferreira, Rebecca Gall, Pin-kuei Fu, Diahn-warng Perng, Flavia Hoyte, Rohit Katial, Unnur Björnsdóttir, Camille Taillé, Christian Taube, Breda Cushen, Lakmini Bulathsinhala, Leif Bjermer, David Price

Asthma characterization using blood eosinophil count (BEC) (among other biomarkers and clinical indices) is recommended in severe asthma (SA), but the masking effect of oral corticosteroids (OCS), makes this challenging. Our aim was to explore the effect of OCS use (both intermittent [iOCS] and long-term [LTOCS]) prior to biologic initiation on SA phenotype and biomarker profile in real-life and to characterize the burden of SA among patients prescribed LTOCS by biomarker profile. This was a registry-based cohort study, including data from 23 countries collected between 2003 and 2023 and shared with the Internatonal Severe Asthma Registry (ISAR). Patients with SA were categorized into 3 cohorts, those with: (i) no prescription for OCS, (ii) prescription(s) for iOCS (ie, ≤90 days in previous 12-months, usually short courses for exacerbations), and (iii) prescriptions for LTOCS (ie, >90 days in previous 12-months). Biomarker distribution (ie, BEC, fractional exhaled nitric oxide [FeNO], and total Immunoglobulin E [IgE]) were quantified in the year prior to biologic initiation in patients with SA according to OCS prescription pattern. Phenotypes were characterized for those prescribed LTOCS according to BEC cut-off (<150 and ≥ 150 cells/μL). Of 4305 patients included, 5.0% (n = 215), 54.1% (n = 2330) and 40.9% (n = 1760) were prescribed no OCS, iOCS, and LTOCS, respectively. The BEC distribution varied by prescription pattern and LTOCS dose (<5 mg to ≥20 mg/day); BEC was <150 cells/μL in 28.6% (n = 369/1288) of LTOCS patients, compared to 19.5% (n = 284/1460) of iOCS patients and 14.0% (n = 21/150) of those in the no OCS group. Median BEC was also significantly lower in the LTOCS versus the iOCS group (310 vs 400 cells/μL; p < 0.001). A similar pattern was noted for IgE, but not FeNO. Among LTOCS patients with BEC <150 cells/μL, 39.9% experienced ≥4 exacerbations, 75.1% had uncontrolled asthma symptoms and 55.9% had evidence of persistent airflow obstruction (compared with 40.9%, 76.2% and 59.5% of those with BEC ≥150 cells/μL, respectively). OCS, whether prescribed intermittently or long term, affect BEC distribution potentially leading to heightened risk of phenotype misclassification and influencing subsequent treatment decisions. FeNO appears to be less susceptible to OCS-induced suppression. Disease burden was high for those in the LTOCS group and was high independent of dose and BEC. Our findings highlight the importance of considering OCS use, even intermittent use, when characterizing SA, and suggests the need for earlier phenotyping and alternative treatment strategies for LTOCS patients with low BEC.