Biologic Treatments for Asthma and Chronic Obstructive Pulmonary Disorder

Abstract

The global COVID-19 pandemic has brought respiratory disease to the forefront of public health, but asthma prevalence has been rising globally for decades. Asthma is mediated by errant immune activation and airway remodeling, but the influences of environment, nutrition, and comorbidities (e.g., asthma-chronic obstructive pulmonary disorder-overlap [ACO]) are still poorly understood. Even as a new generation of biologic-based treatments offer better airway control and reductions in mortality, a lack of prophylactic treatments and mechanistic understanding complicates efforts to prevent pathogenesis. This review will explicate and synthesize current knowledge on the effect of ACO and biologics (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) on pathogenesis, treatment, and prognosis.

Packaging and Delivery of Asthma Therapeutics

“…Sources and Pathway of Asthmatic Exacerbations. Dust, pollen, pet dander, and smo from cigarettes or other sources are potent asthmatic triggers [16,17]. Created in BioRender.com Briefly, mast cell degranulation, interleukin (IL)-4, IL-5 and IL-13 are downstre mediators of asthmatic exacerbations, while CD4+T helper-2 (Th2) cells play a central r in attracting eosinophils that release IL-5 to upregulate IL-4 and IL-13 [17].…”

“…Additionally, tryptase and chymase are released fro mast cells that damage the airway cells with proteolytic action, while the fibrotic respon is triggered by chymase activity on Smad, activating TGF-β [17,21]. This remodeling a activates angiogenesis and the release of fluid into the lumen, swelling the airway a [16,17]. Created in BioRender.com.…”

“…These may be systemic regulators of inflammation (montelukast or pranlukast) or methylxanthines (theophylline) that inhibit phosphodiesterase (Table 1) [35]. However, the use of injectable, monoclonal antibody-derived drugs tailored for specific inhibition of interleukin-dominated inflammation has recently increased following successful clinical trials [16]. This section will briefly review the standard treatments as well as offer some insight on new classes of antibody-derived therapeutics that specifically target T lymphocyte and mast cell-mediated asthmatic inflammation.…”

“…Diverse anti-cytokine drugs, such as anti-TSLP antibody (tezepelumab), anti-IL-33R antibody (CNTO 7160), anti-IL-4Rα antibody (dupilumab), and anti-IL-5 antibody (mepolizumab and reslizumab), have gone or are currently undergoing clinical trials (Table 1) [46]. However, while IL-5-targeted mepolizumab and reslizumab were confirmed by the US Food and Drug Administration as treatments for severe asthma, other results are controversial and extensively reviewed elsewhere [16,64]. Multiple new biologics are also currently under development and are in clinical trials [65].…”

“…COPD is a terminal disease featuring inflammation of the airways and, because of overlapping molecular mechanisms, asthma therapies are often useful to keep airways open. However, COPD patients have reduced inspirative capacity, reduced immune regulatory ability, and a biochemical pathogenesis centered around IL-8, CD8+ T cells, neutrophils, and macrophages versus the IL4-, IL-5, IL-13, and CD4+ T cell-driven phenotype of asthmatics (Figure 6) [16]. These patients thus require combinations of medicines, such as ICS-LABA-LAMA, that may cross-react at a chemical level or counteract each other at a systemic level [174].…”