T2-Low Asthma: A Discussed but Still Orphan Disease

Abstract

Asthma affects 10% of the worldwide population; about 5% of cases are severe with the need for target therapies such as biologics. All the biologics approved for asthma hit the T2 pathway of inflammation. T2-high asthma is classified as allergic and non-allergic, whereas T2-low asthma can be further defined as paucigranulocytic asthma, Type 1 and Type-17 inflammation and the neutrophilic form that accounts for 20-30% of all patients with asthma. Neutrophilic asthma's prevalence is even higher in patients with severe or refractory asthma. We searched Medline and PubMed archives from the past ten years for articles with the subsequent titles: "neutrophilic asthma", "non-type 2 asthma" and "paucigranulocytic asthma". We identified 177 articles; 49 were considered relevant by the title and 33 by the reading of the abstract. Most of these articles are reviews (n = 19); only 6 are clinical trials. No study identified an effective treatment. We used the literature reported by these articles to search for further biologic treatments that target pathways different from T2. We identified 177 articles, 93 of which were considered relevant for the review and included in the present article. In conclusion, T2-low asthma remains poorly investigated in terms of biomarkers, especially as a therapeutic orphan disease.

Keywords: T2-low asthma; non-T2 asthma; orphan disease; refractory asthma.

Figure 1

The process of selecting articles.

Figure 2

Pathogenesis of T2 high and T2-low asthma: IL: interleukin; TNF: tumour necrosis factor; INF: interferon; IgE immunoglobulin E; LTB4: leukotriene B4, CXCL: chemokine (C-X-C motif) ligand, CXCR: C-X-C motif receptor.