Drug screening and high throughput in three-dimensional lung models

Respiratory illnesses are among the commonest chronic diseases, affecting hundreds of millions of people worldwide. Whereas asthma and chronic obstructive pulmonary disease (COPD) are the most prevalent chronic respiratory diseases, the disease burden of lung cancer, idiopathic pulmonary fibrosis, cystic fibrosis, and, more recently, Covid-19 and Long Covid is high, and adequate disease-modifying therapeutics for many of these diseases are lacking. A particularly problematic example is COPD, which is one of the most common lung diseases in the world. It causes 6% of all deaths, and the burden of disease is increasing rapidly, currently affecting over 200 million people. Pharmacological treatment can improve symptoms and exacerbation frequency to some degree but does not improve rate of decline in lung function. In fact, in the past 20 years, only one new drug class (PDE4 inhibitors) has been added to the portfolio of drugs available for the management of COPD, and its effectiveness is limited. The COPD treatment guidelines advocate the use of treatment principles such as long-acting antimuscarinics or long-acting β-adrenergic agonists, with or without inhaled corticosteroids, for the majority of patients. None of these strategies affect the course of the disease (boosting tissue repair or preventing loss of lung function). Strikingly, very few new drugs have made it to phase III clinical trials over the past 10 years, p38MAPK inhibitors being an example. None of the p38MAPK inhibitors have progressed to the market, owing to limited efficacy.