Biomedical Engineering Reference
In-Depth Information
respectively. Nonfibrotic lesions include siderosis, stannosis, and baritosis that are caused by par-
ticles of iron oxide, tin oxide, and barium sulfate, respectively. Among these pulmonary lesions,
silicosis, coal worker's pneumoconiosis, and asbestosis dominate the most common clinical cases.
Over the last three decades, death rates due to asbestosis have increased tremendously, overwhelm-
ing the decrease in death rates due to the other two types of pneumoconiosis. Here, it is to be noted
that these clinical conditions are influenced by a multitude of particle types, varying in size and
concentration. These particulate clouds are mineral and combustion-derived, and are found most
commonly in developing nations. NPs are the most toxic of the particles found in particulate clouds
and are the most significant contributors to fibrogenicity. It is hypothesized that NPs could also
behave like asbestos
in vivo
since some NPs, particularly the carbon rods, have similar shape, size,
and properties. In one study, it has been shown that asbestos-like pathogenic behavior of MWCNTs
in mice induces inflammation and formation of granulomas. Although there have not been any con-
firmed reported clinical cases of engineered NP-induced pulmonary fibrosis, it should be remem-
bered that the rapidly increasing exposure levels may cause serious issues, considering the extent to
which NPs are integrated into technology [27].
20.13.2.3 Exacerbation of Asthma
Asthma is a disease state of lung hypersensitivity caused by inflammation of the airways, making
asthmatic individuals more vulnerable to NP-induced lung toxicity. Many early studies have shown
that deposition of fine particles are most enhanced in the lungs of patients with chronic obstructive
lung disease, including asthma. Since inhaled ultrafine particles (UFPs) have higher deposition effi-
ciency in the pulmonary region, more UFPs are retained in the lung with each breath in comparison
with larger particles. In cases of asthmatic patients, airway obstruction causes air trapping and thus
an increase in alveolar volume, causing a net increase in UFP deposition through diffusion, although
impairment of alveolar ventilation may prove to be inhibitory. Since alveolar volume increases dur-
ing exercise, the deposition in healthy individuals is also higher during exercise than while at rest.
However, this increase is not significant in asthmatic patients, perhaps because the increased alveolar
volume and airway turbulence is inherently present. Dead space ventilation increases the minute res-
piration of patients with obstructive lung disease. This phenomenon along with hyperinflation, which
is seen even in mild cases of asthma, is speculated to increase the diffusional deposition of UFPs in
the distal airways and alveoli. The increase in particle numbers in the lungs has been reported to be
74% in asthmatic patients compared with healthy subjects. Therefore, it would appear that greater NP
deposition in the lungs would exacerbate airway inflammation in susceptible individuals. Another
concern would be how the use of steroids in asthmatic individuals would affect NP lung toxicity.
Steroids, such as the various forms of corticosteroids, are used in the treatment of asthma as it helps
to control and reduce inflammation in the airways by inhibiting cyclooxygenases and production of
superoxides. But how effective steroids are in counteracting NP toxicity is still not known (30).
20.14 CYTOTOXICITY
Cells on exposure to CNTs may result in a variety of cell fates. CNTs are known to cause necrosis,
where cells lose cell membranes and burst rapidly. There have been reports that cells stop growing
or dividing actively, hence losing their viability on treatment with CNTs. Cells can also activate a
genetic program of controlled cell death better known as apoptosis. The probable mechanism of
photothermal killing of cancer cells with CNTs and graphene involved both necrotic and apoptotic
cell death characterized by caspase activation or DNA fragmentation and cell membrane damage
[31]. Apoptosis-associated genes can be upregulated and tyrosine kinase activities can be decreased,
with downregulation of the expression of the related genes. The mechanism of SWCNTs cytotoxicity
has been evaluated in terms of induced changes on cytoskeletons and cell morphology. It is known
that certain proteins such as focal adhesion kinase (FAK) cadherin, collagen, and fibronectin play
an important role in cell adhesion. CNTs introduce themselves into cell membranes and agitate the
