**3. Pulmonary injury and its therapeutical challenges**

The constitution and toxicity of smoke and of products generated by combustion compromise the environmental condition and health of exposed individuals, generating local or systemic affections, which may leave sequelae and even progress to death [2].

Inhalation injury by smoke can happen as a consequence of the high temperature of vapor inhaled, decrease of breathed fraction of oxygen, and presence of toxic gases such as carbon monoxide, sulfur dioxide, nitrogen, and ammonia, absorbed or not by the inhaled particulate matter [6, 7].

There are different damages to the different structures of the respiratory system [8]. In the airways, there is scaling of ciliated pseudostratified epithelium, mucosal edema, bronchorrhea, and tracheobronchial obstruction, increasing resistance and limiting air flow [9]. Sometimes, from the histological point of view, depending on the inhalation injury model, such changes can be reversible.

Regarding pulmonary parenchyma, the injuries are characterized by lung emphysema with expressive thinning of intra-alveolar septa, which burst and increase alveolar spaces. This tissue involvement can have progressive character, caused by the arrival of neutrophils in the pulmonary interstice, generating a superoxide radical, which directly harms the membrane of interstitial cells and the endothelium [10–12]. According to Ferreira and Matsubara [13], production and release of reactive oxygen species contribute to the emphysema.

About 6–7 h after initial exposure, there is an increase of IL-1β and IL-8 concentrations [14]. Besides those, other inflammatory process mediators are tumor necrosis factor-alpha (TNFɑ), IL-6, and nuclear factor-kappa β [2]. The actions of IL-1β, IL-6, and IL-8 stimulate adherence of leucocytes and disseminated intravascular coagulation, with IL-6 highlighted in eosinophil attraction to the injured area [15]. TNF-ɑ is known for being a powerful inflammatory mediator in thermal lesions, inhalation injuries, and generalized infections [16].

Clinical treatment of an inhalation injury is a challenge based on the control of consequences of smoke exposure, there being no gold standard. Some immediate care assures the integrity of organs and systems of victims. It is necessary to start oxygen therapy with hyperoxia (FiO2 = 100%) for a limited time, to discern the indication of artificial airway and invasive or noninvasive ventilatory support, patient pronation, and extracorporeal membrane oxygenation [17].

It is important to maintain airway perversity as well as alveolar stability. The administration of β2-agonist, heparin and N-acetylcysteine nebulization have a role in the management, as well as the more specific treatment of carbon monoxide or cyanide poisoning, have contributed to good therapeutic results [18, 19].

Acknowledging the systemic effects of the condition, the hydration and monitoring of micro and macro hemodynamics are extremely relevant to prevent further complications. Pharmacological treatment is based on the consequences and additional complications. Corticosteroids, antibiotics, anticoagulants, sedatives, and analgesics and, in cases of intoxication by cyanide, hydroxocobalamin, sodium nitrite, sodium thiosulfate, or sodium nitrite, by intravenous route, can be administered [3, 20].

At the experimental level, the use of mesenchymal stem cells derived from human amnion (hAMSCs) alleviated white smoke-induced lung injury [21]. It is

*Intellectual Property Rights - Patent*

dysfunction, this can increase up to 60–80% [2].

occurred in 149 of these patients (1.12%).

tion are discussed in this chapter.

**by smoke inhalation**

from 16 to 30 months [1].

the host's repair mechanisms receive proper support [2].

system [2].

with skin burns exceeding 70% of body surface area, and is mainly caused by inhibited smoke inhalation, which has an extremely toxic effect in the respiratory

The physiopathology of an inhalation injury encompasses multiple factors, and the injured respiratory system can present deterioration in a few hours. If combined with cutaneous burns, the inhalation injury increases even more the incidence of pulmonary complications and the mortality. On average, the mortality from burns is less than 10%, but in the presence of an inhalation injury, this increases up to 25–43%. When complications develop, such as pneumonia and multiple organ

The prevalence of burns is significantly higher in developing countries than in developed. In the USA, nearly 2 million people are burned every year. Of these, about 100,000 have moderate to severe burns, requiring hospitalization, and 70% of fire victims who die within 12 h have an inhalation injury [3, 4]. In an epidemiological study conducted by Iqbal et al. [5], which evaluated 13,295 patients, it was found that men were the majority of the victims (56.43%); the mean age of adults was 33.63 ± 10.76 years and the children's age was 6.71 ± 3.47 years, the domestic environment being the most common (68%). The mean body surface area burned was 10.64 ± 11.45% in total. Smoke inhalation injury

Although many products and techniques have been developed to control cutaneous thermal injury, few specific therapeutical options for diagnosis were found for patients with inhalation injury. Several factors explain the slower improvement progress in the treatment of patients with inhalation injury. Inhalation injury is a more complex clinical problem. The burned cutaneous tissue can be removed and replaced by skin grafts. The injured pulmonary tissue must be protected from a secondary injury due to resuscitation, mechanical ventilation, and infection, while

Many consequences of smoke inhalation result from an inflammatory response involving mediators whose number and functions still remain without a complete understanding, despite enhanced tools to process clinical material. Improvements in mortality by inhalation injury are mainly due widespread improvements in intensive care, instead of interventions focused in smoke inhalation. The search for proper inhalation treatments remains, and the treatments used for smoke inhala-

**2. Intellectual property aimed at the treatment of pulmonary injury** 

sarily, must be fulfilled so the inventor can retain his rights [1].

Intellectual property enables a transformation of knowledge to principle and a link between knowledge and market. It is also said that a patent is the legal document that represents the set of exclusivity rights granted by the State to an inventor. By receiving the patent rights over his product, the inventor also receives several rights and guarantees, however, with these rights also come obligations that, neces-

In case of him not meeting his obligations, he is subject to a mandatory licensing of his invention or utility model. If a patent is requested and granted for technology, of a novelty product or to enhance an invention, there are several proceedings, regulations, and laws to register and grant these patents, which vary for each country, also varying the concession period. The delay in patent granting is pointed as a barrier to innovation in a country. According to the World Intellectual Property Organization (WIPO), the period for an international patent registration varies

**62**

likely that in the future this resource will contribute to the best clinical outcome for victims of this type of injury.

It is known, however, that the best clinical outcome for the victim of inhalation injury depends on other factors. According to Bedri et al. [22], socioeconomic and ethnic factors and the sex of the victims influence the clinical outcome. They found that Afro-descendent Americans, female and uninsured, had more complications, more surgical interventions, longer hospital stay, and higher mortality rates, even though lower body surface area burned and there is a lower proportion of inhaled lesion. These disparities further emphasize the need for further research on the underlying racial and socioeconomic factors that this review of the database could not discern.

In turn, natural products present great therapeutic potential and are the subject of study in several experimental, in vitro, and/or in vivo research. The low cost, the good availability, and the habitual use by the population, considering the regional popular knowledge, are some of the factors that contribute to this reality.

The terpene group deserves special mention, both for being part of traditional medicine for centuries and for having a low toxicity [23]. In addition to being used in the food and cosmetic industries, its effects, anti-inflammatories, antioxidants, analgesics, anticonvulsants, antidepressants, anxiolytics, anticancer, antitumor, neuroprotective, antimutagenic, antiallergic, antibiotics, and antidiabetics, are widely known.

Examples are carvacrol, linalool, borneol, limonene, myrene, and pinene. It is known, for example, that D-limonene has important immunomodulatory properties, ameliorating attacks of atopy and asthma, besides inhibiting the action of cytokines and release of substances reactive to oxygen and containing migration of eosinophils [2, 8].
