**8. References**


are being faced, which, in turn, mean there are still many chances for the academic and

Further research efforts are needed to ensure the safety of long-term in vivo applications. There is an urgent requirement for cautiously designed toxicology and toxicokinetic studies for each nanocarrier type; the protocols should be customized for an appropriate clinical use. Furthermore, it should be pointed out that scale up from laboratory to industry is still poorly investigated in this specific area, despite its obvious importance in the ultimate goal of the development a product that can reach the market and actually give benefits to the

In spite of the above reported difficulties and challenges; hopefully, within a few years, the safety and large - scale production at affordable costs of the delivery technologies described

Augustí, A.G. & Soriano, J.B. (2008). COPD as a systemic disease. *COPD*, Vol. 5, No. 2,

Augustí, A.G., Noguera, A., Sauleda, J., Sala, E., Pons, J. & Busquets, X. (2003). Systemic

Altiere, R.J. & Thompson, D.C. (1996). Pulmonary physiology and pharmacology of the

Azarmi, S., Roa , W. H. & Löbenberg, R. (2008). Targeted delivery of nanoparticles for the

Bansil, R. & Turner, B.S. (2006). Mucin structure, aggregation, physiological functions and

Bansil, R., Stanley, E. & LaMont, J.T. (1995). Mucin Biophysics*. Ann Rev Physiol*, Vol. 57,

Barnes, P.J. & Celli, B.R. (2009). Systemic manifestations and comorbidities of COPD. *Eur* 

Beckham, J.D., Cadena, A., Lin, J, Piedra, P.A., Glezen,W.P., Greenberg, S.B. & Atmar, R.L.

Bruinenberg, P., Serisier, D., Cipolla, D. & Blanchard, J. (2010). Safety, tolerability and

*Med*, Vol. 181, B49 Meeting Abstract, (May 2010), A3192, ISSN 1073-449X.

disease. *J Infect,* Vol. 50, No. 4, (May 2005), pp. 322−330, ISSN 0163-4453. Bernhard, W., Haslam, P.L. & Floros, J. (2004). From birds to humans: new concepts on

*Respir J,* Vol. 33, No. 5, (May 2009), pp 1165-1185, ISSN 0903-1936.

effects of chronic obstructive pulmonary disease. *Eur Respir J*, Vol. 21, No. 2,

airways, In: *Inhalation Aerosols: Physical and Biological Basis for Therapy*, Antony J.

treatment of lung diseases. *Adv Drug Deliv Rev,* Vol. 60, No. 8, (May 2008), pp. 863–

biomedical applications. *Curr. Opin. Colloid Interface Sci.*, Vol. 11, No. 2-3, (June

(2005). Respiratory viral infections in patients with chronic, obstructive pulmonary

airways relative to alveolar surfactant. *Am J Respir Cell Mol Biol*, Vol. 30, No. 1,

pharmacokinetics of novel liposomal ciprofloxacin formulations for inhalation in healthy volunteers and non-cystic bronchiectasis patients. *Am J Respir Crit Care* 

industrial scientist to make a decisive impact.

in this book will be a dream that will become true.

875, ISSN 0169-409X.

2006), pp. 164–170, ISSN 1359-0294.

(March 1995), pp. 635–657, ISSN 0066-4278.

(January 2004), pp. 6–11, ISSN 1044-1549.

(January 2008), pp. 133-138, ISSN 1541-2555.

(February 2003), pp. 347-360, ISSN 0903-1936.

Hickey, pp. 96–99, Informa, ISBN: 0849341604, New York.

patients.

**8. References** 


Gan, W.Q., Man, S.F., Senthilselvan, A. & Sin, D.D. (2004). Association between chronic

Geiser M. & Kreyling, W.G. (2010). Deposition and biokinetics of inhaled naNo.particles. *Part. Fibre Toxicol*, Vol. 7, No. 2, (January 2010), pp. 1-17, ISSN 1743-8977. Geiser, M. (2010). Update on macrophage clearance of inhaled micro- and nanoparticles. *J* 

Geiser, M., Casaulta, M., Kupferschmid, B., Schulz, H., Semmler-Behnke, M. & Kreyling, W.

Gonda, I. (2006). Systemic delivery of drugs to humans via inhalation*. J Aerosol Med*, Vol. 19,

Griesenbach, U. & Alton, E.W. (2009). Gene transfer to the lung: lessons learned from more

Haley, B. & Frenkel, E. (2008). Nanoparticles for drug delivery in cancer treatment. *Urol Oncol*, Vol. 26, No. 1, (January-February 2008), pp. 57-64, ISSN 1078-1439. Heyder, J., Gebhart, J., Rudolf, G., Schiller, C.F. & Stahlhofen, W. (1985). Deposition of

Hinds, W.C. (1999). Uniform Particle Motion. In: *Aerosol Technology: Properties, Behavior and* 

Hogg, J. C., Chu, F., Utokaparch, S., Woods, R., Elliott, W. M. & Buzatu, L. (2004). The nature

Hogg, J.C., Chu, F.S. & Tan, W.C. (2007). Survival after lung volume reduction in chronic

*Crit Care Med*, Vol. 176, No. 4, (August 2007), pp. 454–459, ISSN 1044-1549. Holt, P.G., Strickland, D.H., Wikstrom, M.E. & Jahnsen, F.L. (2008). Regulation of

Huang, C.C., Aronstam, R.S., Chen, D.R. & Huang, Y.W. (2010). Oxidative stress, calcium

Huertas, A. & Palange, P. (2011). COPD: a multifactorial systemic disease. *Ther Adv Respir* 

Illum L. (2002). Nasal drug delivery: new developments and strategies. *Drug Discov Today,* 

*Dis*, Vol. 5, No. 3, (March 2011), pp. 217-224, ISSN 1753-4658.

Vol. 7, No. 23, (December 2002), pp. 1184–1189, ISSN 1359-6446.

*Med*, Vol. 350, No. 26, (June 2004), pp. 2645−2653, ISSN 0028-4793.

ISSN 0340-5761.

376, ISSN: 1044-1549.

No. 1, (March 2006), pp. 47–53, ISSN 0894-2684.

Vol. 17, No. 5, (May 1985), pp. 811–25, ISSN 0021-8502.

2009), pp. 128–139, ISSN 0169-409X.

ISBN 978-0-471-19410-1, New York.

(February 2008), pp. 142–52, ISSN 1474-1733.

0887-2333.

2711.

macrophage-associated routes. *Arch Toxicol*, Vol. 83, No. 5, (May 2009), pp. 429–437,

obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. *Thorax*, Vol. 59, No. 6, (June 2004) pp. 574-580, ISSN 1468-3296.

*Aerosol Med Pulm Drug Deliv*, Vol. 23, No. 4, (August 2010), pp. 207–17, ISSN 1941-

(2008). The role of macrophages in the clearance of inhaled ultrafine titanium dioxide particles. *Am J Respir Cell Mol Biol*, Vol. 38, No. 3, (March 2008), pp. 371–

than 2 decades of CF gene therapy. *Adv Drug Deliv Rev*, Vol. 61, No. 2, (February

particles in the human respiratory tract in the size range 0.005–15 μm. *J Aerosol Sci,* 

*Measurement of Airborne Particles Second ed.,* William C. Hinds, pp. 53–55, Wiley,

of small-airway obstruction in chronic obstructive pulmonary disease. *N Engl J* 

obstructive pulmonary disease: insights from small airway pathology. *Am J Respir* 

immunological homeostasis in the respiratory tract. *Nat Rev Immunol*, Vol. 8, No. 2,

homeostasis, and altered gene expression in human lung epithelial cells exposed to ZnO nanoparticles. *Toxicol In Vitro,* Vol. 24, No. 1, (February 2010), pp. 45–55, ISSN

technology and nanoparticle characteristics on aerosol features. *J Control Release*, Vol. 86, No. 1, (January 2003), pp.131–44, ISSN: 0168-3659.


Darwis, Y. & Kellaway, I.W. (2001). Nebulization of rehydrated freeze-dried beclomethasone

Daviskas, E., Anderson, S.D., Shaw, J., Eberl, S., Seale, J.P., Yang, I.A. & Young, I.H. (2005).

*Respirology*, Vol. 10, No. 4, (September 2005), pp. 426–435, ISSN: 1440-1843. de Vries, A., Dessing, M.C., Engels, F., Henricks, P.A.J. & Nijkamp, F.P. (1999). Nerve

Decramer, M. & Janssens, J. (2010). Mucoactive therapy in COPD. *Eur Respir Rev*, Vol. 19,

Dekhuijzen, P.N. (2004). Antioxidant properties of N-acetylcysteine: their relevance in

Desai, T.R. & Finlay, W.H. (2002). Nebulization of niosomal all-trans-retinoic acid : an

Deshmukh, H. S., Shaver, C., Case, L.M., Dietsch, M., Wesselkamper, S. C. & Hardie,W. D.

Di Marzio, L., Marianecci, C., Cinque, B., Nazzarri, M., Cimini, A.M., Cristiano., L., Cifone,

*Acta*, Vol. 1778, No. 12, (December 2008), pp. 2749–2756 ISSN 0005-2736. Dimitrijevic, D., Shaw, A.J. & Florence, A.T. (2000). Effects of some non-ionic surfactants on

Dumont, J.A., Bitonti, A.J., Clark, D., Evans, S., Pickford, M. & Newman, S.P. (2005).

Edsbäcker, S, Wollmer, P., Selroos, O., Borgstroem, L., Olsson, B. & Ingelf J. (2008). Do

El-Chemaly, S., Pacheco-Rodriguez, G., Ikeda, Y., Malide, D. & Moss, J. (2009). Lymphatics

Evans, C.M. & Koo, J.S. (2009). Airway mucus: the good, the bad, the sticky. *Pharmacol Ther*,

Furuyama, A., Kanno., S., Kobayashi, T. & Hirano., S. (2009). Extrapulmonary translocation

Vol. 7, No. 4, (December 2009),pp. 197–203, ISSN 1539-6851

Vol. 121, No. 3, (March 2009), pp. 332-348, ISSN 0163-7258.

Vol. 86, No. 1, (January 2003), pp.131–44, ISSN: 0168-3659.

(May 1999), pp. 1541–1544, ISSN 1073-449X.

(April 2004), pp. 629–636, ISSN 0903-1936.

(February 2000), pp. 157–162 ISSN 0022-3573

2005), pp. 294–303, ISSN 0894-2684.

1094-553.

2002), pp. 311–317, ISSN 0378-5173.

446−454, ISSN 1044-1549.

No. 116, (June 2010), 134–140, ISSN 0905-9180.

ISSN 0378-5173.

technology and nanoparticle characteristics on aerosol features. *J Control Release*,

dipropionate liposomes. *Int J Pharm,* Vol. 215, No. 1-2, (March 2001), pp. 113–121.

Mucociliary clearance in patients with chronic asthma: effects of beta agonists.

growth factor induces a neurokinin-1 receptor-mediated airway hyperresponsiveness in guinea pigs. *Am J Respir Crit Care Med*, Vol. 159, No. 5,

relation to chronic obstructive pulmonary disease. *Eur Respir J*, Vol. 23, No. 4,

inexpensive alternative to conventional liposomes. *Int J Pharm*, Vol. 241, No. 2 (July

(2008). Acrolein-activated matrix metalloproteinase 9 contributes to persistent mucin production. *Am J Respir Cell Mol Biol*, Vol. 38, No. 4, (April 2008), pp.

M.G., Alhaique, F. & Carafa, M. (2008). pH-sensitive non-phospholipid vesicle and macrophage-like cells: binding, uptake and endocytotic pathway. *Biochim Biophys* 

transepithelial permeability in Caco-2 cells. *J Pharm Pharmacol*, Vol. 52, No. 2,

Delivery of an erythropoietin-Fc fusion protein by inhalation in humans through an immunoglobulin transport pathway. *J Aerosol Med,* Vol. 18, No. 3, (September

airway clearance mechanisms influence the local and systemic effects of inhaled corticosteroids? *Pulm Pharmacol Ther*, Vol. 21, No. 2, (April 2008), pp. 247–258, ISSN

in idiopathic pulmonary fibrosis: new insights into an old disease. *Lymphat Res Biol*,

of intratracheally instilled fine and ultrafine particles via direct and alveolar

macrophage-associated routes. *Arch Toxicol*, Vol. 83, No. 5, (May 2009), pp. 429–437, ISSN 0340-5761.


Mercer, R.R., Russell, M.L., Roggli, V.L. & Crapo, J.D. (1994). Cell number and distribution

Misra, A., Jinturkar, K., Patel, D., Lalani, J. & Chougule, M. (2009). Recent advances in

Mitsopoulos, P. & Suntres, Z. E (2011). Protective effects of liposomal N-acetylcysteine

Montenegro, L., Panico, A.M. & Bonina, F. (1996). Quantitative determination of

Morawska, L., Hofmann, W., Hitchins-Loveday, J., Swanson, C. & Mengersen, K. (2005).

Muhlfeld, C., Gehr, P. & Rothen-Rutishauser, B. (2008). Translocation and cellular entering

Muhlfeld, C., Rothen-Rutishauser, B., Blank, F., Vanhecke, D., Ochs, M. & Gehr, P. (2008).

Neumiller, J.J. & Campbell, R.K. (2010). Technosphere insulin: an inhaled prandial insulin product*. BioDrugs*, Vol. 24, No. 3, (June 2010), pp. 165–172, ISSN 1173-8804. Nguyen, J., Reul, R., Betz, T., Dayyoub, E., Schmehl, T., Gessler, T., Bakowsky, U., Seeger, W.

Nimje, N., Agarwal, A., Saraogi, G.K., Lariya, N., Rai, G., Agrawal, H. & Agrawai, G.P.

*Drug Target*, Vol. 17, No. 10, (December 2009), pp. 777–787, ISSN 1061-186X. Oakley, R.H., Jewell, C.M., Yudt, M.R., Bofetiado, D.M. & Cidlowski, J.A. (1999). The

Oberdörster, G. (2007). Biokinetics and effects of nanoparticles, In: *Nanotechnology —* 

Oberdorster, G., Oberdorster, E. & Oberdorster, J. (2005). Nanotoxicology: an emerging

Oberdorster, G., Stone, V. & Donaldson K. (2007). Toxicology of nanoparticles: a historical

*Deliv*, Vol. 6, No. 1, (January 2009), pp. 71-89, ISSN 1742-5247.

Article ID 808967 (14 pages), ISSN 1687-8205.

138, No. 2, (July 1996), pp.191–197, ISSN 0378-5173.

27-28, (July 2008), pp. 387–391, ISSN 1424-7860.

140, No. 1, (November 2009), pp. 47-54, ISSN 0168-3659.

pp. 15–51, Springer, ISBN 978-1-4020-6074-8, Netherlands.

113, No. 7, (July 2005), pp. 823–839, ISSN 0091-6765.

pp. 27857–27866, ISSN 0021-9258.

859–868, ISSN 0305-7453.

613–624, ISSN 1044-1549.

8502.

0605.

aeruginosa lung infections. *J Antimicrob Chemother,* Vol. 61, No. 4, (April 2008), pp.

in human and rat airways. *Am J Respir Cell Mol Biol*, Vol. 10, No. 6, (June 1994), pp.

liposomal dry powder formulations: preparation and evaluation. *Expert Opin Drug* 

against paraquat-induced cytotoxicity and gene expression. *J Toxicol*, Vol. 2011,

hydrophobic compound entrapment in DPPC liposomes by DSC. *Int J Pharm,* Vol.

Experimental study of the deposition of combustion aerosols in the human respiratory tract. *J Aerosol Sci*, Vol. 36, No. 8, (August 2005), pp. 939–957, ISSN 0021-

mechanisms of nanoparticles in the respiratory tract. *Swiss Med Wkly*, Vol. 138, No.

Interactions of nanoparticles with pulmonary structures and cellular responses. *Am J Physiol Lung Cell Mol Physiol*, Vol. 294, No. 5, (May 2008), pp. 817–829, ISSN 1040-

& Kissel, T. (2009). Nanocomposites of lung surfactant and biodegradable cationic nanoparticles improve transfection efficiency to lung cells*. J Control Release*, Vol.

(2009). Mannosylated nanoparticulate carriers of rifabutin for alveolar targeting. *J* 

dominant negative activity of the human glucocorticoid receptor beta isoform. Specificity and mechanisms of action. *J Biol Chem*, Vol. 274, No. 3, (Septmber 1999),

*Toxicological Issues and environmental safety*, P.P. Simeonova, N. Opopol, M.I. Luster,

discipline evolving from studies of ultrafine particles. *Environ Health Persp*, Vol.

perspective. *Nanotoxicology*, Vol. 1, No. 1, (January 2007), pp. 2–25, ISSN 1743-5390.


Ishitsuka, T, Akita, H. & Harashima, H. (2011). Functional improvement of an IRQ-PEG-

Kim, V, Criner, G.J., Abdallah, H.Y., Gaughan, J.P., Furukawa, S. & Solomides, C.C. (2005).

Klaine, S.J., Alvarez, P.J.J., Batley, G.E., Fernandes, T.F. & Handy, R.D. (2008). Nanomaterials

Lai, S.K., Wang, Y.Y. & Hanes, J. (2009). Mucus-penetrating nanoparticles for drug and gene

Lam, J.K., Liang, W. & Chan, H.K. (2011). Pulmonary delivery of therapeutic siRNA. *Adv* 

Li, P., Liu, D., Sun, X., Liu, C., Liu, Y. & Zhang, N. (2011). A novel cationic liposome

Lin, H., Gebhardt, M., Bian, S., Kwon, K.A., Shim, C.K., Chung, S.J. & Kim D.D (2007).

Lkhasuren, O., Takahashi, K. & Dash-Onolt, L (2007). Occupational lung diseases and the

Lodge, T.P. (1999). Reconciliation of the molecular weight dependence of diffusion and

Madl, A.K. & Pinkerton, K.E. (2009). Health effects of inhaled engineered and incidental

Mall, M., Grubb, B.R., Harkema, J.R., O'Neal, W.K. & Boucher, R.C. (2004). Increased airway

Mannino, D.M., Homa, D.M., Akinbami, L.J., Ford, E.S., & Redd, S.C. (2002). Chronic

Mansour, H.M., Rhee, Y.S. & Wu, X. (2009). Nanomedicine in pulmonary delivery. *Int J Nanomedicine*, Vol. 4, (December 2009), pp. 299–319, ISSN 1176-9114. Meers, P., Neville, M., Malinin, V., Scotto, A.W., Sardaryan, G., Kurumunda, Mackinson, R.,

*Med,* Vol. 10, No. 4, (April 2004), pp. 487–493, ISSN 1078-8956.

Vol. 47, No. 10, (October 2002), pp.1184−1199, ISSN 0020-1324.

22, No. 24, (June 2011), art. No. 245104 (11 pages), ISSN 1361-6528.

*Chem,* Vol. 27, No. 9, (September 2008), pp. 1825–1851, ISSN 0730-7268. Kurmi, B.D., Kayat, J., Gajbhiye, V., Tekade, R.K. & Jain, N.K. (2010). Micro- and

ISSN 0168-3659.

2005), pp. 40−47, ISSN 1044-1549.

2010), pp. 781-794, ISSN 1742-5247.

*Drug Deliv Rev,* Article in Press, ISSN 0169-409X.

158–171, ISSN 0169-409X.

23–31, ISSN 0378-5173.

2007), pp. 195–201, ISSN 1077-3525.

3218–3221, ISSN 0031-9007.

1040-8444.

MEND for delivering genes to the lung. *J Control Release*, Vol. 154, No. 1, pp. 77-83,

Small airway morphometry and improvement in pulmonary function afterlung volume reduction surgery. *Am J Respir Crit Care Med,* Vol. 171, No. 1, (January

in the environment: Behavior, fate, bioavailability, and effects. *Environ Toxicol* 

nanocarrier-mediated lung targeting. *Expert Opin Drug Deliv*, Vol. 7, No. 7, (July

delivery to mucosal tissues. *Adv Drug Deliv Rev*, Vol. 61, No. 2, (February 2009), pp.

formulation for efficient gene delivery via a pulmonary route. *Nanotechnology,* Vol.

Enhancing effect of surfactants on fexofenadine HCl transport across the human nasal epithelial cell monolayer, *Int J Pharm*, Vol. 330, No. 1-2, (February 2007), pp.

mining industry in Mongolia. *Int J Occup Environ Health,* Vol. 13, No. 2, (April

viscosity in entangled polymers. *Phys Rev Lett,* Vol. 83, No. 16, (October 1999), pp.

nanoparticles. *Crit Rev Toxicol*, Vol. 39, No. 8, (September 2009), pp. 629–658, ISSN

epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice. *Nat* 

obstructive pulmonary disease surveillance—United States, 1971–2000. *Respir Care,*

James, G., Fisher, S. & Perkins, W.R. (2008). Biofilm penetration, triggered release and in vivo activity of inhaled liposomal amikacin in chronic Pseudomonas aeruginosa lung infections. *J Antimicrob Chemother,* Vol. 61, No. 4, (April 2008), pp. 859–868, ISSN 0305-7453.


Rogers, D.F. (2007). Physiology of airway mucus secretion and pathophysiology of

Rossiter, A., Howard, C.P., Amin, N., Costello, D.J. & Boss A.H. (2010). Technosphere®

Santucci, E., Carafa, M., Coviello, T., Murtas, E., Riccieri, F.M., Alhaique, F., Modesti, A. &

Schmid, O., Moller, W., Semmler-Behnke, M., Ferron, G.A., Karg, E., Lipka, J., Schulz, H.,

particles. *Biomarkers, Vol.* 14, No. 1, (July 2009), pp. 67–73, ISSN 1354-750X. Schmidt, S.R. (2009). Fusion-proteins as biopharmaceuticals–applications and challenges.

Shao, M.X., Nakanaga, T. & Nadel, J.A. (2004). Cigarette smoke induces MUC5AC mucin

Sin, D.D. & Man, S.F. (2003). Why are patients with chronic obstructive pulmonary disease

Stamenkovic, I. (2003). Extracellular matrix remodelling: the role of matrix

Sung, J.C., Pulliam, B.L. & Edwards, D.A. (2007). Nanoparticles for drug delivery to the

Tetley,T.D. (2002). Macrophages and the pathogenesis of COPD. *Chest*, Vol. 121, No. 1,

Tsapis, N., Bennett, D., Jackson, B., Weitz, D.A. & Edwards, D.A. (2002). Trojan particles:

Unfried, K., Albrecht, C., Klotz, L.O., Von Mikecz, A., Grether-Beck, S., Schins, R.P.F. (2007).

van der Velden, V. & Hulsmann, A.R. (1999). Peptidases: structure, function and modulation

Verdugo, P. (1990). Goblet cells secretion and mucogenesis. *Ann Rev Physiol,* Vol. 52 (March

*Nanotoxicology*, Vol. 1, No. 1, (January 2007), pp. 51-71, ISSN 1743-5390. Van der Schans, C.P. (2007). Bronchial mucus transport. *Respir Care*, Vol. 52, No. 9,

0020-1324.

June 2010.

6733.

9896.

7799.

pp. 29–32, ISSN 1157-1489.

2, (August 2004), pp. 420−427, ISSN 1040-0605.

(June 2003), pp. 1514-1519, ISSN 0009-7322.

(January 2002), pp. 156S–159S, ISSN 0012-3692.

(September 2007), pp. 1150–1156, ISSN 0020-1324.

(April 1999), pp. 445–456, ISSN 1365-2222.

1990), pp.157–176, ISSN 0066-4278.

No. 19, (September 2002), pp. 12001–12005, ISSN 0027-8424.

hypersecretion. *Respir Care*, Vol. 52, No. 9, (September 2007), pp. 1134–1146, ISSN

Insulin: Safety in Type 2 Diabetes Mellitus. *ADA Scientific Sessions*, Orlando Florida,

Modica, A. (1996). Vesicles from polysorbate 20 and cholesterol. A simple preparation and a characterization. *STP Pharma Sci,* Vol. 6, No. 1, (January 1996),

Kreyling, W.G. & Stoeger, T. (2009). Dosimetry and toxicology of inhaled ultrafine

*Curr Opin Drug Discov Dev*, Vol. 12, No. 2, (March 2009), pp. 284–295, ISSN 1367-

overproduction via tumor necrosis factor-alpha-converting enzyme in human airway epithelial (NCI-H292) cells. *Am J Physiol Lung Cell Mol Physiol,* Vol. 287, No.

at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease. *Circulation,* Vol. 107, No. 6,

metalloproteinases. *J Pathol*, Vol. 200, No. 4, (July 2003), pp. 448–464, ISSN 1096-

lungs. *Trends Biotechnol,* Vol. 25, No. 12, (December 2007), pp. 563–570, ISSN 0167-

large porous carriers of nanoparticles for drug delivery. *Proc Natl Acad Sci*, Vol. 99,

Cellular responses to nanoparticles: target structures and mechanisms.

of peptide-mediated effects in the human lung. *Clin Exp Allergy*, Vol. 29, No. 4,


Okusanya, O.O., Bhavnani, S.M., Hammel, J., Minic, P., Dupont, L.J., Forrest, A., Mulder,

Palange, P., Testa, U., Huertas, A., Calabro`, L., Antonucci, R. & Petrucci, E. (2006).

Paolino, D., Cosco, D., Muzzalupo, R., Trapasso, E., Picci, N. & Fresta, M. (2008). Innovative

Paolino, D., Muzzalupo, R., Ricciardi, A., Celia, C., Picci, N. & Fresta, M. (2007). In vitro and

Patton, J.S. & Byron, P.R. (2007). Inhaling medicines: delivering drugs to the body through

Perez-Gil, J. (2008). Structure of pulmonary surfactant membranes and films: the role of

Quinton, P.M. (2008). Cystic fibrosis: impaired bicarbonate secretion and mucoviscidosis. *Lancet*, Vol. 372, No. 9636 (August 2008), pp. 415–417, ISSN 0140-6736. Rahman, I & Kilty, I. (2006). Antioxidant therapeutic targets in COPD. *Curr Drug Targets,*

Rahman, I., Skwarska, E. & MacNee, W. (1997). Attenuation of oxidant/antioxidant

Remels, A.H., Gosker, H.R., van der Velden, J., Langen, R.C. & Schols, A.M. (2007). Systemic

*Chest Med,* Vol. 28, No. 3, (September 2007), pp. 537-552, ISSN 0272-5231. Robinson, M., Eberl, S., Tomlinson, C., Daviskas, E., Regnis, J.A., Bailey, D.L., Torzillo, P.J.,

Rogers, D.F. & Barnes, P.J. (2006). Treatment of airway mucus hypersecretion. *Ann Med,* Vol.

disease. *Thorax,* Vol. 52, No. 6, (June 1997), pp. 565–568, ISSN 1468-3296. Randell, S.H. & Boucher, R.C. (2006). Effective mucus clearance is essential for respiratory

Vol. 7, No. 6 (June 2006), pp. 707–720, ISSN 1389-4501.

38, No. 2, (January 2006), pp.116–125, ISSN 0785-3890.

*Eur Respir J.* Vol. 27, No. 3 (March 2006), pp. 529-541, ISSN 0903-1936. Palko, H.A., Fung, J.Y. & Louie, A.Y. (2010). Positron emission tomography: a novel

*Toxicol,* Vol. 22, No. 8, (July 2010), pp. 657–688, ISSN 0895-8378.

No. 9, (September 2009), pp. 3847–3854, ISSN 0066-4804.

ISSN 0378-5173.

1474-1776.

1549.

075061403X, Oxford, UK.

pp. 1676–1695, ISSN 0005-2736.

G.J, Mackinson, C., Ambrose, P.G., Gupta, R. (2009). Pharmacokinetic and pharmacodynamic evaluation of liposomal amikacin for inhalation in cystic fibrosis patients with chronic pseudomonal infection. *Antimicrob Agents Chemother*, Vol. 53,

Circulating haemopoietic and endothelial progenitor cells are decreased in COPD.

technique for investigating the biodistribution and transport of nanoparticles. *Inhal* 

bolasurfactant niosomes as topical delivery systems of 5-fluorouracil for the treatment of skin cancer. *Int J Pharm,* Vol. 353, No. 1-2, ( April 2008), pp. 233–242,

in vivo evaluation of Bola-surfactant containing niosomes for transdermal delivery. *Biomed. Microdevices,* Vol. 9, No. 4 (August 2007), pp. 421–433, ISSN 1387-2176. Parkes, W.R. (1994). Morphology of the respiratory tract, In: *Occupational lung disorders*,

Butterworth-Heinemann, pp. 1-17, Butterworth-Heinemann Medical, ISBN

the lungs. *Nat Rev Drug Discov,* Vol*.* 6, No. 1, (January 2007), pp. 67 – 74, ISSN

proteins and lipid–protein interactions. *BBA*, Vol. 1778, No. 7-8, (July-August 2008),

imbalance during treatment of exacerbations of chronic obstructive pulmonary

health. *Am J Respir Cell Mol Biol,* Vol. 35, No. 1, (July 2006), pp. 20–28, ISSN 1044-

inflammation and skeletal muscle dysfunction in chronic obstructive pulmonary disease: State of the art and novel insights in regulation of muscle plasticity. *Clin* 

Menache, M. & Bye, P.T. (2000). Regional mucociliary clearance in patients with cystic fibrosis. *J. Aerosol Med.,* Vol. 13, No. 2, (June 2000), pp. 73–86, ISSN 0894-2684.


**17** 

*Turkey* 

Zeynep Zeren Ucar

**Noninvasive Positive-Pressure** 

*The Department of Pulmonary Disease and Sleep Disorders,* 

 *Dr Suat Seren Chest Diseases and Surgery Training and Research Hospital, Izmir* 

**Ventilation Therapy in Patients with COPD** 

Noninvasive positive pressure ventilation (NPPV) refers to the administration of ventilatory support without using an invasive artificial airway (endotracheal tube or tracheostomy tube). The use of NPPV has markedly increased over the past two decades. Rudimentary devices that provided continuous positive airway pressure were described in the 1930s, but the negative-pressure ventilators were the predominant method of ventilatory support until the polio epidemics overwhelmed their capacity in the 1950s. In the 1980s, increasing experience with positive-pressure ventilation delivered through a mask in patients with obstructive sleep apnea led to this type of ventilatory support, initially in patients with neuromuscular respiratory failure. Success led to its adoption in other conditions, and NPPV became especially promising in the treatment of patients with exacerbations of

NPPV is defined as ventilatory support delivered by a non-invasive interface such as mask or similar device, acting as an alternative to intubation or tracheostomy. Consequently, by avoiding tracheal intubation, NPPV presents several potential advantages, such as reduction in pulmonary infections, barotrauma and need for sedation (British Thoracic Society Standards of Care Committee 2002). As a result, NPPV should be considered a standard of care to treat COPD exacerbation in selected patients, since it markedly reduces the need for intubation and improves outcome by lowering complication and mortality rates, and shortening hospital stay (Brochard et al. 1995; Kramer et al. 1995; Celikel et al. 1998; Martin et al. 2000; Conti et al. 2002; Squadrone et al. 2004; Lightowler et al. 2003; Nava, Navalesi, & Conti 2006). Weaker evidence indicates that NPPV could allow earlier extubation, avoid reintubation in patients who fail extubation, and assist do-not-intubate patients, and thus could be beneficial for COPD patients who are suffering respiratory failure precipitated by superimposed pneumonia or postoperative complications, and COPD patients with severe stable disease who have substantial daytime hypercapnia and superimposed nocturnal

This chapter will examine the evidence pertaining to the use of NPPV for various applications in COPD and make recommendation on patient, ventilation mode and interface selection as well as technical aspects of NPPV application in COPD. The literature review

**1. Introduction** 

hypoventilation.

chronic obstructive pulmonary disease (COPD).

