Akira Tsuda, principal research scientist in the Molecular and Integrative Physiological Sciences Program in the Department of Environmental Health at HSPH.

Akira Tsuda, principal research scientist in the Molecular and Integrative Physiological Sciences Program in the Department of Environmental Health at HSPH.

Infant lungs prone to nanoparticle deposits

April 2, 2012

Findings may have implications for how drugs are delivered to infants

A new study led by a Harvard School of Public Health (HSPH) researcher reveals for the first time how airflow patterns in infant lungs differ from those of adults. The discovery may explain why the lungs of babies are particularly susceptible to deposits of nanoparticles—whether beneficial particles, like inhaled medicines, or harmful ones, like air pollution.

The discoveries one day could lead to improved ways to administer aerosol medications to infants and babies, according to senior author Akira Tsuda, principal research scientist in the Molecular and Integrative Physiological Sciences Program in the Department of Environmental Health at HSPH.

“A large body of epidemiological data demonstrates that children are one of the most susceptible groups to the detrimental health effects of air pollution, but currently there is no explanation of why this age group would be at higher risk. This study provides the first clue on this matter,” Tsuda said.

The study, “Nanoparticle Delivery in Infant Lungs,” was published March 12, 2012 online in the Proceedings of the National Academy of Sciences.

Dramatic changes occur in the geometry of the developing lungs after birth. Images of 4 days old (left), 21 days old (middle), and adult (right) rat lungs, taken by light microscopy (upper row) and by scanning electron microscopy (lower row). Original source: Fig. 1 of Proc. Natl. Acad. Sci.USA. 109(13):5092-5097, 2012. Copyright: PNAS

Tsuda’s group collaborated with scientists at the Helmholtz Zentrum München-German Research Center for Environmental Health in Munich, Germany, where the experiments were conducted in laboratory animals. The latest study is a continuation of an investigation that Tsuda and his colleagues at HSPH began about a decade ago. In 1995 they developed a theory regarding “chaotic mixing” of alveolar flow. The theory describes the internal rotation that, the researchers found, occurs in the alveoli (tiny air sacs) as inhaled particle-laden air mixes with gas already in the lungs, resulting in the deposit of particles in the lungs.

In the new study, the researchers found that because the structure of airways changes dramatically from shallow alveoli to deeper as the lungs develop, at a certain stage of development, the alveolar airflow becomes chaotic. This leads to significant mixing of the particles in the inhaled air with the residual gas and, consequently, to increased deposits of particles on the alveolar walls.

In the case of inhalation drug therapy, there is a need to accurately determine the delivered drug dose, Tsuda said. “Our findings show that the method commonly used in clinical setting for dose estimation for infants—based on simply scaling the infant’s body mass to that of an adult—is inaccurate, and potentially leads to significant overdoses in babies of approximately 2 years of age. Our findings should be considered for optimization of particle design and drug dose,” he said.

Other HSPH researchers participating in the National Institutes of Health-funded study include Frank Henry, research associate in environmental health, and James Butler, senior lecturer on physiology.

Read an article describing the research in Chemistry World.

Read coverage of the research in The Mainichi Daily News (Japan).

–Marge Dwyer

photo: Aubrey LaMedica