Unanswered questions regarding the AIR strategy in children - Authors' reply.

# Unanswered questions regarding the AIR strategy in children – Authors' reply *The Lancet 2026* Correspondence 7 Reddel HK, O’Byrne PM, FitzGerald JM, et al. aged 12–15 years compared with those 2 Beasley R, Holliday M, Reddel HK, et al, and the Efficacy and safety of as-needed budesonide- aged 5–11 years, should be interpreted Novel START Study Team. Controlled trial of formoterol in adolescents with mild asthma. budesonide–formoterol as needed for mild J Allergy Clin Immunol Pract 2021; 9: 3069–77. with appropriate caution as repeated asthma. N Engl J Med 2019; 380: 2020–30. statistical testing could inflate type 3 O’Byrne PM, FitzGerald JM, Bateman ED, et al. Authors’ reply I error. Furthermore, this significant Inhaled combined budesonide–formoterol as needed in mild asthma. N Engl J Med 2018; We thank Stéphanie Lejeune and interaction does not imply an absence 378: 1865–76. colleagues for their insightful of benefit in the younger group; rather, 4 Martinez FD, Chinchilli VM, Morgan WJ, et al. Use of beclomethasone dipropionate as rescue comments on the Article1 reporting that the treatment effect between treatment for children with mild persistent the CARE study, and welcome the them differs by more than would be asthma (TREXA): a randomised, double-blind, placebo-controlled trial. Lancet 2011; opportunity to clarify the points raised. expected by chance alone. 377: 650–57. Maintenance low-dose inhaled The Symbicort Rapihaler 5 Pavord ID, Beasley R, Agusti A, et al. After corticosteroid plus as-needed (AstraZeneca, Cambridge, UK; asthma: redefining airways diseases. Lancet 2018; 391: 350–400. salbutamol is proposed as a more budesonide 50 μg–formoterol 3 μg) appropriate control than as-needed is no longer commercially available. salbutamol, given the not-so-mild This inaccessibility does not reduce the Complement status of the trial population. Although strength of the evidence of the efficacy we acknowledge that many of the and safety of budesonide–formoterol biomarkers during CARE study participants would have reliever therapy in childhood asthma, iptacopan treatment qualified for inhaled corticosteroid although it does mean that alternative treatment according to current pressurised metred-dose inhalers or dry asthma guidelines, this did not powder inhalers would need to be used We read with interest the Article1 happen in clinical practice; none of in current clinical practice. by David Kavanagh and colleagues the participants had used medication Several randomised controlled trials showing that the complement containing inhaled corticosteroid for of budesonide–formoterol reliever- factor B inhibitor iptacopan at least 6 months before enrolment. based regimens in children are significantly reduces proteinuria in Treatment was not de-escalated for the underway and will provide additional patients with C3 glomerulopathy.1 purposes of the study and participants evidence for anti-inflammatory With its approval, the reach of in the control group continued their reliever therapy across the spectrum of complement inhibitors continues to See Online for appendix pre-study salbutamol monotherapy. asthma severity (appendix). expand, underscoring their emerging The results of our trial are therefore role in diseases previously considered RB has received personal fees from AstraZeneca, generalisable to clinical practice Avillion, and Teva, and institutional research not complement-mediated or and to this at-risk population. They funding from AstraZeneca (including the ongoing untreatable.2 While the authors START CARE study), Teva, Health Research Council also reflect the wider issues of non- commendably included complement of New Zealand, CureKidz NZ, and the Barbara prescribing of (or poor adherence to) Basham Medical Charitable Trust (managed by biomarkers and repeat biopsies, they inhaled corticosteroid medication and Perpetual Guardian). All other authors declare no failed to comprehensively examine competing interests. of defining asthma as mild based on their value for monitoring and guiding current medication use. We also note *Lee Hatter, Karen Oldfield, therapy. that our eligibility criteria were broadly Mark Weatherall, Andrew Bush, In patients treated with iptacopan, consistent with those of similar clinical Richard Beasley plasma soluble C5b-9 levels fell by trials in both children and adults.2–4 lee.hatter@mrinz.ac.nz two-thirds and serum C3 nearly Preventing severe asthma attacks is a Medical Research Institute of New Zealand, doubled, yet glomerular C3 deposition priority in managing asthma; however, Newtown, Wellington 6242, New Zealand decreased only slightly (–0·78 on a (LH, KO, RB); School of Biological Sciences, Victoria we also echo the sentiments of the 12-point scale).1 Whether greater University Wellington, Wellington, New Zealand Lancet Commission on asthma in that (LH, RB); Department of Medicine, Otago University biomarker changes correlated with there should be zero tolerance for any Wellington, Wellington, New Zealand (MW); Royal greater reductions in proteinuria Brompton & Harefield NHS Foundation Trust, asthma attacks.5 To this end, our primary was not reported, leaving their London, UK (AB); National Heart and Lung Institute, outcome included moderate and severe Imperial College London, London, UK (AB); clinical utility unclear. Moreover, attacks to reflect the substantial burden Te Whatu Ora Capital, Coast and Hutt Valley, the discordant responses between Wellington, New Zealand (RB); Faculty of Medicine, on patient symptoms, health-care circulating and tissue complement University of Southampton, Southampton, UK (RB) use, and missed school or work days biomarkers raise a fundamental 1 Hatter L, Holliday M, Oldfield K, et al, and the associated with these events. CARE study team. Budesonide–formoterol question: in C3 glomerulopathy, is The interaction analysis for the versus salbutamol as reliever therapy in children effective complement inhibition with mild asthma (CARE): a 52-week, open- primary outcome, which showed a required primarily in the circulation or label, multicentre, superiority, randomised greater treatment effect in children controlled trial. Lancet 2025; 406: 1473–83. (also) within the kidney? 1234 --- [PDF原文](https://sci-net.xyz/storage/7932541/2b4234ad318e9d25d4fa31230464487dfa883a40d32cfaee3371bbe0ec69e2b4/Unanswered-questions-regarding-the-AIR-strategy-in-children-Authors-reply.pdf) DOI: 10.1016/S0140-6736(26)00242-4