# Air Quality Effects on Human Health and Approaches for Its Assessment through Microfluidic Chips
## 5 OoC for Assessing Health Effects
### OoC Technology for Modeling Lung Pathologies and Pollutant Exposure  
Notably, a number of diseases linked to the exposure to pollutants were successfully modeled in microfluidic systems by using the discussed lung-chips. Various diseases, including asthma, are accompanied by lung inflammation that includes the infiltration of polymorphonuclear eosinophils. In chronic asthma, these cells contribute to pathological airway remodeling by releasing toxic proteins that cause changes in pulmonary surfactant and damage to airway tissue. In their study, [PERSON] and colleagues were able to mimic the migration of eosinophils across the blood-tissue barrier in the airways, and also, to study the effect of a secreted factor known as eosinophil cationic protein [152]. Although these mechanisms only represent one aspect of the asthma etiology, the proposed experimental set up allows for their study in unprecedented detail.  
Inflammatory processes also accompany the progress of COPD. In their work, [PERSON] and colleagues used cells from healthy and COPD donors in their lung-on-a-chip device [151]. They were thus able to recreate inflammatory processes and neutrophil recruitment, both being characteristic in the development of COPD. Most notably, it was possible to use this system for the screening of new anti-inflammatory drugs that might contribute to the treatment options regarding COPD. Building on this model, the effect of cigarette smoke on cells from healthy and COPD donors was investigated [18]. For this, a device was engineered that mimics respiration characteristics of a human smoking a cigarette. The smoke was then transferred into the airway compartment of the lung-on-a-chip to successfully recreate smoking associated pathologies. This approach could, in theory, be applied to other sources containing airborne mixed pollutants, such as exhaust fumes from diesel engines.  
Using their breathing chip design, [PERSON] and colleagues were able to recreate interleukin-2 (IL-2) induced vascular leakage that eventually leads to pulmonary edema. In addition, it was demonstrated that mechanical cyclic stretching, due to breathing, plays an important role in the development of IL-2 induced lung edema [161]. Since IL-2 is administered in cancer patients, severe side effects should be avoided. Here, the authors were able to identify new treatment options for the pulmonary toxicity of IL-2, thus demonstrating the feasibility of using OoC technology for gaining better mechanistical understanding of pathologies and subsequent drug screening. The same breathing chip design was used to demonstrate that nanoparticle translocation from alveoli to the blood stream requires cyclic stretching of the epithelial-endothelial barrier [154]. This study shows the value of including tissue specific physical parameters into organ-on-chip devices, and also highlights how in vitro models can be expanded to closer recreate the in vivo situation.  
Other disease models include hereditary lung diseases, such as cystic fibrosis, or simulate the occlusion and reopening of airways which accompanies the deficiency or dysfunction of pulmonary surfactant during various lung pathologies [159; 160].  
In summary, the use of OoC technology in the context of investigating lung function and pathology is feasible. Factors that might limit the full reconstruction of organ function in lung models include the physiological complexity of the tissue of interest, and the low availability of primary cell material. Since lung is a barrier tissue, the addition of immune cells, such as macrophages, would help to increase the physiological relevance of the respective models. However, current models are already useful for investigating the effect of airborne pollutants on alveolar cells and their potential transfer into the blood stream, and thus, the possibility of their system-wide distribution.