Aerosols, delivery

Coxiella burnetii is a highly infectious bacterium. A single bacterial cell can produce clinical illness. For this reason it is a very strong candidate for use by terrorists via aerosol delivery. While the incubation period is 2 to 14 days, the average is 7 days. In rare instances, incubation period can extend up to 1 month. After infection and proliferation in the lungs, the organisms are picked up by macrophages and carried to the lymph nodes, and from there to the bloodstream. 

This bacterium can produce numerous types of toxins that cause a range of medical problems. The most potent toxin of C. perfringens is the alpha toxin — the one most likely to be used by terrorists. It would be lethal by aerosol delivery. 

Chapter 4 described methods for limiting the time of exposure to weapons of mass destruction that utilize no explosives (e.g., aerosol delivery) or use of conventional explosives (e.g., dirty bomb). The basic procedure is to leave the contaminated area as quickly as possible, enter a nearby building to shelter against airborne contamination, remove soiled articles of clothing, and wash all exposed body parts (including the mouth and hair) as soon as possible. In Chapter 4, the time factor is applied primarily to limit the chances of potential future health effects. In this section, the time factor is applied after a nuclear explosion to prevent serious bodily harm and death. 

The following rules provide guidance on how emergency responders can best minimize exposure to weapons of mass destruction that utilize no explosives (e.g., aerosol delivery of agent) or use conventional explosives (e.g., dirty bomb) ... 

Ben-Jebria A, Eskew ML, Edwards DA (2000) Inhalation systems for pulmonary aerosol delivery in rodents using large porous particles. Aerosol Sci Technol 32 421-433. 

Dahlback M, Eirefelt S, Nerbrink O (1996) Aerosol delivery to the respiratory tract in experimental animals. In Marijnissen JCM, Gradon L (eds.) Aerosol Inhalation Recent Research Frontiers. Kluwer academic publishers, Netherlands, pp 235-246. 

Hickey AJ, Carcia-Contrenas L (2001) Immunological and toxicological implications of short-term studies in animals of pharmaceutical aerosol delivery to the lungs relevance to humans. Crit Rev Ther Drug Carrier Syst 18 387-431. 

Tronde A, Krondahl E, von Euler-Chelpin H, Brunmark P, Bengtsson UH, Ekstrom G, Lennernas H (2002) High airway-to-blood transport of an opioid tetrapeptide in the isolated rat lung after aerosol delivery. Peptides 23 469-478. 

Johnson, M., Fluticasone Propionate Pharmaeokinetic and Pharmaeodynamie Implieations of Different Aerosol Delivery Systems. Proc. Respiratory Drug Delivery VI, Interpharm Press, Buffalo grove, IL, 1998, pp. 61-70. 

Salbutamol Aerosol delivery by microprocessor control (SmartMist ) 29... 

Everard, M.L., Stammers, J., Elardy, J.G., and Milner, A.D., New aerosol delivery system from neonatal ventilator circuits, Dis. Childhood, 67 826-830 (1992). 

Fuller, H.D., Dolovich, M.B., Posmituck, G., Wong, Pack, W., and Newhouse, M.T., Pressurized aerosol versus jet aerosol delivery to mechanically ventilated patients. Am. Rev. Resp. Dis., 142 440-444 (1990). 

Many reviews on the relevant technical aspects for drug nebulization are available (e.g. [43 5]. The greatest disadvantages of nebulizers are their poor deposition efficiency (see Section 3.11) and low output rate (e.g. [46]). Several developments have been reported to improve their efficacy, like the use of open vents or breath-assisted open vents [47] and adapted aerosol delivery [48]. A renewed interest in nebulizer therapy may also come from the generation of special aerosols, such as hposomes [49]. 

Table 3. Aerosol delivery devices (modification of National Institutes of Health, 1997) ...

Answer Aerosol delivery of the CFTR gene. Both viruses and liposome-DNA complexes are capable of successful CFTR gene transfer to the nasal and airway epithelia of patients with CF. In fact, gene transfer to the airways is one of the few areas where liposome-DNA complexes match the expression obtained using viral vectors without the viruses inflammatory side effects. Current trials are aimed at optimizing gene delivery with reduced toxicity to produce sustained correction of the epithelial transport defect. 

Densmore, C.L., Orson, F.M., Xu, B., et al. (2000). Aerosol delivery of robust polyethylene-imine-DNA complexes for gene therapy and genetic immunization. Mol. Then, 1, 180-188. 

Depending on the particle morphology, several administration methods can be used aerosol, inhalation, and systemic- and subcutaneous injections. Typically, particles in the range of 5 to 100 pm are subcutaneously injectable, 1-5 pm particles are suitable for aerosol delivery and... 

Of 335 patients with type 1 diabetes randomized to receive preprandial inhaled insulin as a dry powder formulation via an aerosol delivery system (Exubera) plus bedtime subcutaneous Ultralente insulin, or to continue NPH and regular insulins subcutaneously, 170 received inhaled insulin (mean age 33 years) (272). Six discontinued inhaled insulin, one because of mild cough, two because of hypoglycemia, and three because of insufficient responses. The risk of hypoglycemia was slightly lower in those who used inhaled insulin, at 8.6 events per month compared with 9.0 events per month in the conventional insulin group. 

Figure 1 Typical metered-dose aerosol delivery system.

McDonald RJ, Liggitt HD, Roche L et al (1998) Aerosol delivery of lipid DNA complexes to lungs of rhesus monkeys. Pharm Res 15 671-679... 

Jin H, Kim T, Hwang S et al (2006) Aerosol delivery of urocanic acid-modified chitosan/ programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice. Mol Cancer Ther 5(4) 1041... 

Gerrity, T. R. Pathophysiological and disease constraints on aerosol delivery, in Respiratory Drug Delivery. Boca Raton, FL CRC Press, 1990. 

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