How Environmental Chemicals Shape Our Respiratory Health
The air we breathe may be silently influencing lung development from our earliest days.
Imagine the intricate process of lung development as an elaborate architectural blueprint. Now imagine various environmental chemicals subtly altering that blueprint, sometimes with lifelong consequences. This isn't a hypothetical scenario—a growing body of scientific evidence reveals that exposure to certain chemicals during critical developmental windows can reprogram the very foundation of our respiratory system. The implications are profound: altered lung function in infancy can predict pulmonary health throughout an entire lifetime.
The human lung doesn't simply inflate like a balloon at birth. It undergoes an exquisitely timed, multi-stage construction process that begins in the womb and continues into childhood.
The initial lung buds emerge from the foregut, like the first sketches of a complex architectural plan.
The branching structure of major airways forms, creating the conducting pathway for future air exchange.
Respiratory bronchioles and air sacs begin to develop, alongside the crucial blood supply network.
Primitive air sacs develop where oxygen exchange will eventually occur.
True alveoli—the tiny grape-like clusters where gas exchange occurs—multiply dramatically, increasing the lung's surface area.
This developmental process depends on highly conserved signaling pathways and growth factors that orchestrate branching morphogenesis and alveolarization. When environmental chemicals disrupt these fundamental biologic processes, the architectural plan can be altered, sometimes permanently.
The old paradigm of toxicology—"the dose makes the poison"—has been complicated by our understanding of developmental timing. The same exposure that would have negligible effect on an adult can cause significant disruption to a developing organism during critical windows of susceptibility.
Lung function in infancy predicts pulmonary function throughout life. In utero and early postnatal exposures influence both childhood and adult lung structure and function and may predispose individuals to chronic obstructive lung disease and other disorders 1 .
Several sizable studies from various countries have demonstrated that lung function in both asthmatics and nonasthmatics tracks from early childhood through adolescence and up to midlife, and is set by early-life events 2 .
The nutritional and endogenous chemical environment affects development of the lung and can result in altered function in the adult. Studies now suggest that similar adverse impacts may occur in animals and humans after exposure to environmentally relevant doses of certain xenobiotics during critical windows in early life 3 .
A compelling 2025 study published in Scientific Reports provides a striking example of how chemicals can disrupt normal lung development, even when administered for legitimate medical purposes.
Researchers designed an elegant experiment to test whether heparin—a commonly used anticoagulant in neonatal care—might interfere with postnatal lung development:
The results were clear and concerning. Both forms of heparin administered during the critical saccular phase produced an emphysematous lung phenotype—characterized by enlarged airspaces and impaired gas exchange—that persisted into juvenile stages. Importantly, heparin administration after the saccular phase did not impact lung function or growth, highlighting the irrecoverable nature of this specific developmental window.
| Lung Function Parameter | Control Group | UFH Group | LMWH Group |
|---|---|---|---|
| Compliance (μL/cmH₂O) | 0.016 ± 0.00059 | 0.019 ± 0.00083* | 0.03 ± 0.001* |
| Elastance (mL/cmH₂O) | 65.52 ± 2.78 | 52.63 ± 2.37* | 33.0 ± 1.4* |
| Inspiratory Capacity (μL) | 0.32 ± 0.0077 | 0.39 ± 0.014* | 0.57 ± 0.02 |
| Lung Volume (μL/g) | 73.7 ± 3.0 | 64.2 ± 1.7* | 62.2 ± 1.5* |
| Morphometric Parameter | Control Group | UFH Group | Change |
|---|---|---|---|
| Normalized Alveolar Volume (μL/g) | 2.2 ± 0.2 | 1.7 ± 0.1 | -23% |
| Parenchymal Volume (μL/g) | 5.4 ± 0.4 | 4.0 ± 0.2 | -26% |
| Architectural Appearance | Normal | Emphysematous | Enlarged airspaces |
The mechanism behind this disruption appears related to heparin's anti-angiogenic properties—its ability to inhibit the formation of new blood vessels. Lung development depends on coordinated angiogenesis driven by vascular endothelial growth factor (VEGF), and heparin is known to interfere with VEGF signaling. This disruption of epithelial-endothelial crosstalk results in abnormal alveolarization.
Heparin represents just one example of potential developmental disruptors. The chemical environment contains numerous agents that may impact lung development through various mechanisms:
These fine airborne particles can deposit deep in the alveoli and trigger inflammatory responses. A 2024 study revealed that PM2.5 exposure induces significant changes in both lung and gut microbiota, creating a "gut-lung axis" of inflammation that amplifies injury 4 .
Chemicals that interfere with hormonal signaling can alter the sexually dimorphic aspects of lung development. For instance, androgens slow surfactant production—explaining why male infants have higher rates of respiratory distress syndrome 5 .
Compounds like benzo(a)pyrene activate the aryl hydrocarbon receptor (AhR), triggering toxicity pathways that can lead to oxidative stress and tissue damage in developing lungs 6 .
| Research Tool | Function/Application |
|---|---|
| BMDExpress | Analyzes dose-response data from gene expression experiments |
| GeoTox | Characterizes risk from spatially-referenced stressor mixtures |
| DNT-DIVER | Hosts developmental neurotoxicity data (related to lung tox) |
| ChemMaps.com v2.0 | Navigates chemical space for risk assessment |
| OPERA | Suite of QSAR models predicting toxicity endpoints |
The evidence clearly indicates that assessing environmental chemical impacts on the lung requires studies that evaluate specific alterations in structure or function—end points not regularly assessed in standard toxicity tests. This knowledge should enable policies promoting true primary prevention of lung diseases.
Identifying effects on important signaling events may inform protocols of developmental toxicology studies. Evidence of relevant signaling disruption in the absence of adequate developmental toxicology data should influence the size of the uncertainty factors used in risk assessments.
The most vulnerable periods are during pregnancy and early childhood when lungs are developing rapidly.
Supporting policies that reduce environmental pollutants benefits respiratory health across generations.
The revelation that environmental chemicals can reshape the fundamental architecture of developing lungs is both concerning and empowering. As we better understand these connections, we gain opportunities to intervene—through smarter chemical testing, targeted regulations, and increased public awareness. The goal is not simply to treat lung disease, but to prevent it at its earliest origins, ensuring that every pair of lungs gets the healthiest possible start.
The editorial "No exposure left behind: time to pay attention to children's chemical environment in lung development" in the European Respiratory Journal puts it perfectly: we must pay attention to the chemical environment in which children's lungs develop. After all, the ability to breathe freely is one of life's most fundamental rhythms—a rhythm worth protecting from our very first breath to our last 7 .