{"doi":"10.1002/ppul.26918","title":"Allergen immunotherapy in patients with severe asthma: A need for prospective trials","abstract":"Allergen immunotherapy (AIT) alters the immune response to environmental allergens directly through mast cell desensitization, and indirectly through the induction of immunologic tolerance. First described in 1911,1 it has been extensively studied for its cost effectiveness, safety, and tolerability.2, 3 While on monthly immunotherapy injections, patients have significant reductions in asthma symptoms, medication use, and improvement in bronchial hyperreactivity.4-8 After completion of 3 years of AIT, most patients achieve sustained effects of treatment despite discontinuation of AIT. AIT remains the only disease-modifying intervention for children with asthma and allergic rhinitis.7 Current National Heart, Lung, and Blood Institute (NHLBI) asthma treatment guidelines recommend consideration of subcutaneous AIT in treatment steps 2, 3, and 4.9 Patients with severe asthma on NHLBI treatment steps 5 and 6 are typically excluded from AIT because uncontrolled asthma is a risk factor for allergic reactions during AIT.9-11 Asthma, even when controlled, is a risk factor for anaphylaxis in patients undergoing immunotherapy9, 12, 13 and asthma is a risk factor for fatal outcomes during anaphylactic events.9, 12 While the risk of anaphylaxis can be mitigated by using safer immunotherapy protocols, the concern about using immunotherapy in patients with severe asthma is warranted.14 Children on NHLBI treatment steps 5 and 6 comprise 5% of pediatric asthma but account for nearly 50% of asthma-related costs due to increased need for medications and healthcare utilization.15 The relative contraindication of immunotherapy in patients with severe asthma means that those with the largest predicted effect size are not routinely offered this treatment option. It is important to note that the recommendations to avoid immunotherapy in patients with severe asthma predate the widespread use of biologic therapies. Using biological medications to achieve control of asthma as a bridge to immunotherapy has been successfully reported.11, 16-20 It has not yet been studied whether children who take a biologic medication for their asthma can stop their biologic (step down) after induction of AIT therapy. Because AIT is a disease modifying treatment modality for children with asthma, this merits investigation. One potential benefit of AIT is that children with asthma who complete AIT can successfully step down to lower steps of treatment regimens, ultimately requiring fewer inhaled medications or lower doses of inhaled medications.21, 22 Prospective clinical trials are needed to determine whether children with severe asthma can safely use biological medications to initiate immunotherapy, and subsequently discontinue the biological medications as the disease modifying effects of immunotherapy are seen. Because severe asthma requiring biological medications is rare, and the centers that use this approach are widely distributed, a multisite trial is needed to power this study. Because AIT is not under patent and the intention is to determine whether the more costly monoclonal antibodies used to maintain control of severe asthma can be stopped, such a study would not be supported by the pharmaceutical industry. Public funding for such a trial is needed. Children that would most benefit from treatment (i.e., those with transportation as a barrier for care, those coming from rural communities, and those from underserved communities) should be included to determine the breadth of benefit of using this approach. If successful, a trial that demonstrated the effectiveness of immunotherapy to decrease the severity of asthma in children would change asthma guidelines, decrease overall healthcare expenditures, and improve the lives of those most affected by this common medical condition. Study conception and design: Margaret Huntwork and John Carlson. Draft manuscript preparation: Margaret Huntwork and John Carlson. Supervision/oversight: John Carlson. Both authors review","journal":"Pediatric Pulmonology","year":2024,"id":479481,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":782880,"name":"John C. Carlson","orcid":"0000-0001-8965-071X","position":1,"is_corresponding":false},{"id":1140683,"name":"Margaret Huntwork","orcid":"0000-0003-2211-1281","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-19T02:06:54.284166Z","pmid":"38358039","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}