The exploration of respiratory diseases is a complex field that demands an understanding of both the human body and various animal models. Research into these diseases is crucial as they represent a significant health burden globally, including chronic conditions like asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. These conditions often require innovative treatments, and animal models play a pivotal role in the development of these therapies.

Eleonore Fröhlich from the Medical University of Graz has contributed a comprehensive review of the importance of animal models in respiratory research. Published in the International Journal of Molecular Sciences, this review sheds light on how animal models have been, and continue to be, essential in understanding respiratory diseases and developing new treatments.

“Despite significant advances in alternatives to in vivo testing, animal studies are still the gold standard for toxicity testing and drug development,” says Professor Fröhlich. Her analysis outlines the key differences in respiratory anatomy and physiology among commonly used mammalian models and highlights their respective advantages and limitations.

One of the most significant challenges in respiratory research is the anatomical and physiological differences between humans and animals. These differences can influence how diseases develop and how treatments work. For instance, while mice are commonly used in respiratory research due to their low costs and possibility to generate transgenic animals, their small size and different respiratory physiology can limit the direct applicability of findings to human health. Larger animals, such as pigs and non-human primates, offer closer anatomical and physiological similarities to humans, but ethical concerns and higher costs make their use more challenging. 

The review also discusses the historical context of animal experimentation, tracing its origins back to ancient times. Over the centuries, the use of animals in medical research has evolved, with significant contributions to the development of vaccines, anesthetics, and various therapeutic protocols. However, as the review notes, the ethical considerations surrounding animal testing have also grown, leading to increased efforts to reduce, refine, and replace animal use (3Rs) in research wherever possible.

Professor Fröhlich emphasizes that while alternatives to animal testing, such as in vitro studies and computational models, have advanced significantly, they cannot yet fully replicate the complexity of living organisms. For example, animal models remain crucial for understanding how inhaled substances affect the entire respiratory system, something that cannot be easily simulated in a lab environment.Improved cellular exposure systems, physiologically more relevant cell culture systems, and novel systems such as fish and fly models that can bridge the gap between in vitro and traditional mammalian models have been developed. However, it takes time to establish them as validated systems with high reproducibility.  “Given this, a complete replacement of animal studies does not seem realistic in the near future,” she remarks.

In the context of respiratory diseases, different animal species offer unique insights. Mice are particularly valuable in studying diseases like asthma and pulmonary fibrosis. However, for other respiratory diseases such as COPD or cystic fibrosis, larger animals like pigs or non-human primates are more suitable. These animals have respiratory systems that more closely mimic human anatomy, making them better models for studying disease progression and testing new therapies. Although not possessing lungs, invertebrates can provide insight into specific features of respiratory diseases.

The study also touches upon the future of respiratory research, suggesting that a combination of mammalian and non-mammalian animal models, in vitro systems, and computational approaches will likely be the way forward. This integrative approach could reduce the reliance on animal models while still providing the necessary insights to develop effective treatments for respiratory diseases.

According to her, biological test systems should be selected based on the specific characteristics of the diseases. After extensive testing in advanced cellular systems and  non-mammalian models (where appropriate), the  compound should be tested in the most relevant mammalian disease model.

Journal Reference

Fröhlich, Eleonore. “Animals in Respiratory Research.” International Journal of Molecular Sciences, 2024. 

DOI: https://doi.org/10.3390/ijms25052903

About the Author

Eleonore Fröhlich is Professor of Anatomy, Histology and Embryology at the University of Tübingen, Director of the Core Facility Imaging at the Center for Medical Research at the Medical University of Graz and Key Researcher at the K1 Competence Center for Excellent Technologies, the Center for Pharmaceutical Engineering in Graz. Her research activities include studies on the toxicity of nanoparticles in various in vitro systems, the biological assessment of inhaled formulations and the role of thyroid hormones in humans. In her role as Chairperson of the Animal Welfare Body of the Medical University of Graz according to Directive 2010/63/EU, she aims to contribute to the 3Rs and to provide a balanced view on the use of animals in research.