Abstract
In times of increasing costs for health insurances, obstructive lung diseases are a burden for both the patients and the economy. Pulmonary symptoms of asthma and chronic obstructive pulmonary disease (COPD) are similar; nevertheless, the diseases differ in pathophysiology and therapeutic approaches. Novel therapeutics are continuously developed, and nonhuman primates (NHPs) provide valuable models for investigating novel biologicals regarding efficacy and safety.This review discusses the role of nonhuman primate models for drug development in asthma and COPD and investigates whether alternative methods are able to prevent animal experiments.
Highlights
Shortness of breath, wheezing, coughing, and chest tightness – these are the symptoms that affect 300 million people worldwide, with the reasons being obstructive lung diseases
Pulmonary symptoms of asthma and chronic obstructive pulmonary disease (COPD) are similar; the diseases differ in pathophysiology and therapeutic approaches
COPD is categorized according to reduced lung function, the nature of the patient’s symptoms, and the risk of exacerbation (GOLD, 2017)
Summary
Shortness of breath, wheezing, coughing, and chest tightness – these are the symptoms that affect 300 million people worldwide, with the reasons being obstructive lung diseases. Asthma symptoms occur due to airway obstruction either after an acute stimulus, e.g., an allergen, or as a result of chronic remodeling processes. An acute asthmatic response occurs within minutes after allergen exposure, leading to reduced lung function due to airway obstruction, designated as early airway response (EAR). Allergens induce cross linking of mast cell bound immunoglobulin E (IgE), resulting in a release of mast cell mediators These lead to airway obstruction by smooth muscle contraction, vasodilation, and increased vascular permeability. Whereas mild and moderate asthma are well controlled by inhaled corticosteroids and long-acting betaagonists (LABAs), severe asthma is largely therapy resistant In these patients, alternative approaches involve application of therapeutic antibodies targeting IgE (omalizumab) and IL5 (mepolizumab, reslizumab) (Brusselle and Bracke, 2014). To increase comparability to human allergic patients, further asthma models in nonhuman primates comprise experimental sensitization with allergens of house dust mites (HDMs, Dermatophagoides pteronyssinus and Dermatophagoides farinae; Yasue et al, 1998; Schelegle et al, 2001; Van Scott et al, 2004; Iwashita et al, 2008) and birch pollen (Bet V1 and Bet V2; Ferreira et al, 1996)
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