400
Views
14
CrossRef citations to date
0
Altmetric
Review Article

The long and winding road to inhaled TB therapy: not only the bug’s fault

, &
Pages 347-363 | Received 16 Sep 2016, Accepted 09 Dec 2016, Published online: 05 Jan 2017

References

  • WHO/HTM/TB/2015.22. 2015. Global tuberculosis report 2015. Available from: https://www.health-e.org.za/wp-content/uploads/2015/10/Global-TB-Report-2015-FINAL-2.pdf
  • Sullivan ZA, Wong EB, Ndungua T, et al. Latent and Active tuberculosis infection increase immune activation in individuals co-infected with HIV. EBioMedicine 2015;2:334–40.
  • Migliori GB, De Iaco G, Besozzi G, et al. First tuberculosis cases in Italy resistant to all tested drugs. Eurosurveillance 2007;12:3194.
  • Udwadia ZF, Amala RA, Ajbani KK, Rodrigues C. Totally drug-resistant tuberculosis in India. Clin Infect Dis 2012;54:579–81.
  • Parida SK, Axelsson-Robertson R, Rao MV, et al. Totally drug-resistant tuberculosis and adjunct therapies. J Intern Med 2015;277:388–405.
  • Saviola B. Mycobacterium tuberculosis adaptation to survival in a human host. In: Mahboub BH, Vats MG, ed. Tuberculosis: current issues in diagnosis and management. InTech; 2013: 3–18. Available from: http://www.intechopen.com/books/tuberculosis-current-issues-in-diagnosis-and-management/mycobacterium-tuberculosis-adaptation-to-survival-in-a-human-host
  • Ehlers S, Schaible UE. The granuloma in tuberculosis: dynamics of a host-pathogen collusion. Front Immunol 2013;3:411.
  • Silva MM, Breiman A, Allain S, et al. The tuberculous granuloma: an unsuccessful host defence mechanism providing a safety shelter for the bacteria? Clin Dev Immunol 2012;2012:139127.
  • Ramakrishnan L. Revisiting the role of the granuloma in tuberculosis. Nature Rev Immunol 2012;12:352–66.
  • Brighenti S, Lerm M. How Mycobacterium tuberculosis manipulates innate and adaptive immunity: new views of an old topic. In: Cardona PJ, ed. Understanding tuberculosis: analyzing the origin of Mycobacterium tuberculosis pathogenicity. InTech Open; 2012: 207–34. Available from: http://www.intechopen.com/books/understanding-tuberculosis-analyzing-the-origin-of-mycobacterium-tuberculosis-pathogenicity/how-mycobacterium-tuberculosis-manipulates-innate-and-adaptive-immunity-new-views-of-an-old-topic
  • Adewale SO, Podder CN, Gumel AB. Mathematical analysis of a TB transmission model with DOTS. Can App Math Q 2009;17:1–36.
  • Feng Z, Castillo-Chavez C. A model for tuberculosis with exogenous reinfection. Theor Pop Biol 2000;57:235–47.
  • Bru A, Cardona PJ. Mathematical modeling of tuberculosis bacillary counts and cellular populations in the organs of infected mice. PLoS One 2010;5:e12985.
  • Castillo-Chavez C, Song B. Dynamical models of tuberculosis and their applications. Math Biosci Eng 2004;1:361–404.
  • Mlay GM, Luboobi LS, Kuznetsov D, Shahada F. The role of re-infection in modeling the dynamics of one-strain tuberculosis involving vaccination and treatment. Asian J Math Appl 2014;2014:ama0205.
  • Cardona PJ, Vilaplana C. Multiple consecutive infections might explain the lack of protection by BCG. PLoS One 2014;9:e94736.
  • Cardona PJ. A dynamic reinfection hypothesis of latent tuberculosis infection. Infection 2009;37:80–6.
  • Delogu G, Sali M, Fadda G. The biology of Mycobacterium tuberculosis infection. Mediterr J Hematol Infect Dis 2013;5:e2013070.
  • Smits K, Corbière V, Dirix V, et al. Immunological signatures identifying different stages of latent Mycobacterium tuberculosis infection and discriminating latent from active tuberculosis in humans. J Clin Cell Immunol 2015;6:341.
  • Evangelopoulos D, da Fonseca JD, Waddell SJ. Understanding anti-tuberculosis drug efficacy: rethinking bacterial populations and how we model them. Int J Infectious Dis 2015;32:76–80.
  • Raffetseder J, Pienaar E, Blomgran R, et al. Replication rates of Mycobacterium tuberculosis in human macrophages do not correlate with mycobacterial antibiotic susceptibility. PLoS One 2014;9:e112426.
  • Dartois V. The path of anti-tuberculosis drugs: from blood to lesions to mycobacterial cells. Nat Rev Microbiol 2014;12:159–67.
  • Lakshminarayana SB, Huat TB, Ho PC, et al. Comprehensive physicochemical, pharmacokinetic and activity profiling of anti-TB agents. J Antimicrob Chemother 2015;70:857–67.
  • Patton JS, Byron PR. Inhaling medicines: delivering drugs to the body through lungs. Nat Rev 2007;6:67–74.
  • Lippmann M, Yeates DB, Albert RE. Deposition, retention, and clearance of inhaled particles. Br J Ind Med 1980;37:337–62.
  • Patton JS. Mechanisms of macromolecule absorption by the lungs. Adv Drug Deliv Rev 1996;19:3–36.
  • Patton JS, Byron PR. Inhaling medicines: delivering drugs to the body through the lungs. Nat Rev Drug Discov 2007;6:67–74.
  • Gonda I. Systemic delivery of drugs to humans via inhalation. J Aerosol Med 2006;19:47–53.
  • Albanna AS, Smith BM, Cowan D, et al. Fixed-dose combination antituberculosis therapy: a systematic review and meta-analysis. Eur Respir J 2013;42:721–32.
  • Garcia-Contreras L, Smyth HDC. Liquid-spray or dry-powder systems for inhaled delivery of peptide and proteins? Am J Drug Deliv 2005;3:29–45.
  • Morrow PE, Yu CP. Models of aerosol behavior in airways. In: Moren F, Newhouse MT, Dolovich MB, eds. Aerosols in medicine. Amsterdam: Elsevier; 1985:149–91.
  • Palmes ED, Altshuler B, Nelson N, Deposition of aerosols in the human respiratory tract during breath holding. In: Davies CN, ed. Inhaled particles and vapours II. New York: Pergamon Press; 1967:339–49.
  • Hogg JC. Response of the lung to inhaled particles. Med J Aust 1985;142:675–8.
  • Newman S, Agnew JE, Pavia D, Clarke SW. Inhaled aerosols: lung deposition and clinical applications. Clin Phys Physiol Meas 1982;3:1–20.
  • Heyder J. Deposition of inhaled particles in the human respiratory tract and consequences for regional targeting in respiratory drug delivery. Proc Am Thorac Soc 2004;1:315–20.
  • Carvalho TC, Peters JI, Williams RO, 3rd. Influence of particle size on regional lung deposition–what evidence is there? Int J Pharm 2011;406:1–10.
  • Fernández Tena A, Casan Clarà P. Deposition of inhaled particles in the lungs. Arch Bronconeumol 2012;48:240–6.
  • Christensen WD, Swift DL. Aerosol deposition and flow limitation in a compliant tube. J Appl Physiol 1986;60:630–7.
  • Labiris NR, Dolovich MB. Pulmonary drug delivery. Part II: the role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol 2003;56:600–12.
  • Dolovich MB, Dhand R. Aerosol drug delivery: developments in device design and clinical use. Lancet 2011;377:1032–45.
  • Ibrahim M, Verma R, Garcia-Contreras L. Inhalation drug delivery devices: technology update. Med Dev Ev Res 2015;8:131–9.
  • Garvey C, Fahy B, Lareau S, et al. Using your metered dose inhaler (MDI). Am J Respir Crit Care Med 2014;190:P5–6.
  • Yang MY, Chan JGY, Chan H-K. Pulmonary drug delivery by powder aerosols. J Control Release 2014;193:228–40.
  • Sanchis J, Corrigan C, Levy ML, et al. Inhaler devices: from theory to practice. Respir Med 2013;107:495–502.
  • Bell JH, Hartley PS, Cox JS. Dry powder aerosols. I. A new powder inhalation device. J Pharm Sci 1971;60:1559–64.
  • Jet AA. Ultrasonic, and mesh nebulizers: an evaluation of nebulizers for better clinical outcomes. Eurasian J Pulmonol 2014;16:1–7.
  • Dhand R. Intelligent nebulizers in the age of the internet: the I-neb adaptive aerosol delivery (AAD) system. J Aerosol Med Pulm Drug Del 2010;23(Suppl1):iii–v.
  • Naehrig S, Lang S, Schiffl H, et al. Lung function in adult patients with cystic fibrosis after using the eFlow® rapid for one year. Eur J Med Res 2011;16:63–6.
  • Rose JE, Turner JE, Murugesan T, et al. Pulmonary delivery of nicotine pyruvate: sensory and pharmacokinetic characteristics. Exp Clin Psychopharmacol 2010;18:385–94.
  • Cipolla D, Gonda I. Inhaled nicotine replacement therapy. Asian J Pharm Sci 2015;10:472–80.
  • Farr SJ, Otulana BA. Pulmonary delivery of opioids as pain therapeutics. Adv Drug Deliv Rev 2006;58:1076–88.
  • Overhoff KA, Clayborough R, Crowley M. Review of the TAIFUN® multidose dry powder inhaler technology. Drug Dev Ind Pharm 2008;34:960–5.
  • Lee W-H, Loo C-Y, Traini D, Young PM. Inhalation of nanoparticles-based drug for lung cancer treatment: advantages and challenges. Asian J Pharm Sci 2015;10:481–9.
  • Goel A, Baboota S, Sahni JK, Ali J. Exploring targeted pulmonary delivery for treatment of lung cancer. Int J Pharm Investig 2013;3:8–14.
  • Garbuzenko OB, Saad Pozharov VP, et al. Inhibition of lung tumor growth by M complex pulmonary delivery of drugs with oligonucleotides as suppressors of cellular resistance. PNAS 2010;107:10737–42.
  • Drug delivery technologies market by application (Oral, Pulmonary, Transdermal, Injectable, Nasal, Implantable & Others): growth, share, opportunities & competitive analysis, 2015–2022. April 2016; Report Code: 57779-04-16. Available from: http://www.credenceresearch.com/report/drug-delivery-technologies-market
  • Klick JM, du Moulin GC, Hedley-Whyte J, et al. Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis. II. Effect on the incidence of pneumonia in seriously ill patients. J Clin Invest 1975;55:514–19.
  • Sands P, Mundaca-Shah C, Dzau VJ. The neglected dimension of global security: A framework for countering infectious-disease crises. N Engl J Med 2016;374:1281–7.
  • Cipolla D, Froehlich J, Gonda I. Emerging opportunities for inhaled antibiotic therapy. J Antimicrob 2015:1:104.
  • Quon BS, Goss CH, Ramsey BW. Inhaled antibiotics for lower airway infections. Ann Am Thorac Soc 2014;11:425–34.
  • Agent P, Parrott H. Inhaled therapy in cystic fibrosis: agents, devices and regimens. Breathe (Sheff) 2015;11:110–18.
  • Zampieri FG, Nassar AP Jr, Gusmao-Flores D, et al. Nebulized antibiotics for ventilator-associated pneumonia: a systematic review and meta-analysis. Critical Care 2015;19:150.
  • Velkov T, Rahima NA, Zhou Q, et al. Inhaled anti-infective chemotherapy for respiratory tract infections: successes, challenges and the road ahead. Adv Drug Deliv Rev 2015;85:65–82.
  • Wenzler E, Fraidenburg DR, Scardina T, Danziger LH. Inhaled antibiotics for Gram-negative respiratory infections. Clin Microbiol Rev 2015;29:581–632.
  • Cipolla D, Chan HK. Inhaled antibiotics to treat lung infection. Pharm Pat Anal 2013;2:647–63.
  • Karvouniaris M, Makris D, Triantaris A, Zakynthinos E. Inhaled antibiotics for nosocomial pneumonia. Inflamm Allergy Drug Targets 2012;11:116–23.
  • Cipolla D, Blanchard J, Gonda I. Development of liposomal ciprofloxacin to treat lung infections. Pharmaceutics 2016;8:6.
  • Uttley L, Tappenden P. Dry powder inhalers in cystic fibrosis: same old drugs but different benefits? Curr Opin Pulm Med 2014;20:607–12.
  • Bodnár R, Mészáros A, Oláh M, Ágh T. Inhaled antibiotics for the treatment of chronic Pseudomonas aeruginosa infection in cystic fibrosis patients: challenges to treatment adherence and strategies to improve outcomes. Patient Prefer Adherence 2016;10:183–93.
  • Elborn JS. Ciprofloxacin dry powder inhaler in cystic fibrosis. BMJ Open Resp Res 2016;3:e000125.
  • De Soyza A, Aksamit T. Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis. Exp Opin Orph Drugs 2016;4:875–84.
  • Santos V, Cardoso AV, Damas C. Clinical and functional impact of inhaled antibiotics in a Portuguese pulmonology department. Rev Port Pneumol 2016;22:242–3.
  • Naesens R, Vlieghe E, Verbrugghe W, et al. A retrospective observational study on the efficacy of colistin by inhalation as compared to parenteral administration for the treatment of nosocomial pneumonia associated with multidrug-resistant Pseudomonas aeruginosa. Inf Dis 2011;11:317.
  • Moreno-Sastre M, Pastor M, Salomon CJ, et al. Pulmonary drug delivery: a review on nanocarriers for antibacterial chemotherapy. J Antimicrob Chemother 2015;70:2945–55.
  • Paranjpe M, Müller-Goymann CC. Nanoparticle-mediated pulmonary drug delivery: a review. Int J Mol Sci 2014;15:5852–73.
  • Kuzmov A, Minko T. Nanotechnology approaches for inhalation treatment of lung diseases. J Control Release 2015;219:500–18.
  • Lee SH, Teo J, Heng D, et al. Tailored antibiotic combination powders for inhaled rotational antibiotic therapy. J Pharm Sci 2016;105:1501–12.
  • Lee SH, Teo J, Heng D, et al. Steroid-decorated antibiotic microparticles for inhaled anti-infective therapy. J Pharm Sci 2014;103:1115–25.
  • Tewes F, Brillault J, Lamy B, et al. Ciprofloxacin-loaded inorganic − organic composite microparticles to treat bacterial lung infection. Mol Pharmaceutics 2016;13:100–12.
  • Cipolla D, Froehlich J, Gonda I. Emerging opportunities for inhaled antibiotic therapy. J Antimicrob Agents 2015;1:104.
  • Klinger-Strobel M, Lautenschlager C, Fischer D, et al. Aspects of pulmonary drug delivery strategies for infections in cystic fibrosis – where do we stand? Expert Opin Drug Deliv 2015;12:1351–74.
  • Weers J, Tarara T. The PulmoSphere™ platform for pulmonary drug delivery. Ther Deliv 2014;5:277–95.
  • Pulmatrix.inc. Pulmatrix receives orphan drug designation from the US FDA for inhaled drug to treat pulmonary fungal infections in cystic fibrosis patients. Aug. 17 2016 (http://www.pulmatrix.com/isperse_platform.html).
  • Pilcer G, Amighi K. Formulation strategy and use of excipients in pulmonary drug delivery. Int J Pharm 2010;392:1–19.
  • Ziffels S, Bemelmans NL, Durhamc PG, Hickey AJ. In vitro dry powder inhaler formulation performance considerations. J Control Release 2015;199:45–52.
  • Paraf J, Zivy P, Paraf M, et al. Value of stable aerosols of antibiotics in the treatment of pulmonary tuberculosis; physico-chemical data on the problem and first results. Bull Mem Soc Med Hop Paris 1953;69:211–21.
  • Pham DD, Fattal E, Tsapis N. Pulmonary drug delivery systems for tuberculosis treatment. Int J Pharm 2015;478:517–29.
  • Hickey AJ, Durham PG, Dharmadhikari A, et al. Inhaled drug treatment for tuberculosis: Past progress and future prospects. J Control Release 2016;240:127–34.
  • Sacks LV, Pendle S, Orlovic D, et al. Adjunctive salvage therapy with inhaled aminoglycosides for patients with persistent smear-positive pulmonary tuberculosis. Clin Infect Dis 2001;32:44–9.
  • Das S, Tucker I, Stewart P. Inhaled dry powder formulations for treating tuberculosis. Curr Drug Deliv 2015;12:26–39.
  • Hanif SN, Garcia-Contreras L. Pharmaceutical aerosols for the treatment and prevention of tuberculosis. Front Cell Infect Microbiol 2012;2:118.
  • Mortensen NP, Durham P, Hickey AJ. The role of particle physico-chemical properties in pulmonary drug delivery for tuberculosis therapy. J Microencapsul 2014;31:785–95.
  • Mehanna MM, Mohyeldin SM, Elgindy NA. Respirable nanocarriers as a promising strategy for antitubercular drug delivery. J Control Release 2014;187:183–97.
  • Gupta A, Pandya SM, Mohammad I, et al. Particulate pulmonary delivery systems containing anti-tuberculosis agents. Crit Rev Ther Drug Carrier Syst 2013;30:277–91.
  • Son YJ, McConville JT. A new respirable form of rifampicin. Eur J Pharm Biopharm 2011;78:366–76.
  • Parikh R, Patel L, Dalwadi S. Microparticles of rifampicin: comparison of pulmonary route with oral route for drug uptake by alveolar macrophages, phagocytosis activity and toxicity study in albino rats. Drug Deliv 2014;21:406–11.
  • Garcia Contreras L, Sung J, Ibrahim M, et al. Pharmacokinetics of inhaled rifampicin porous particles for tuberculosis treatment: insight into rifampicin absorption from the lungs of guinea pigs. Mol Pharm 2015;12:2642–50.
  • Pham DD, Fattal E, Ghermani N, et al. Formulation of pyrazinamide-loaded large porous particles for the pulmonary route: avoiding crystal growth using excipients. Int J Pharm 2013;454:668–77.
  • Pham DD, Grégoire N, Couet W, et al. Pulmonary delivery of pyrazinamide-loaded large porous particles. Eur J Pharm Biopharm 2015;94:241–50.
  • Durham PG, Zhang Y, German N, et al. Spray dried aerosol particles of pyrazinoic acid salts for tuberculosis therapy. Mol Pharmaceutics 2015;12:2574–81.
  • Chan JGY, Tyne AS, Pang A, et al. A rifapentine-containing inhaled triple antibiotic formulation for rapid treatment of tubercular infection. Pharm Res 2014;31:1239–53.
  • Sung JC, Garcia-Contreras L, Verberkmoes JL, et al. Dry powder nitroimidazopyran antibiotic PA-824 aerosol for inhalation. Antimicrob Agents Chemother 2009;53:1338–43.
  • Garcia-Contreras L, Sung JC, Muttil P, et al. Dry powder PA-824 aerosols for treatment of tuberculosis in guinea pigs. Antimicrob Agents Chemother 2010;54:1436–42.
  • Ní Cheallaigh C, Keane J, Lavelle EC, et al. Autophagy in the immune response to tuberculosis: clinical perspectives. Clin Exp Immunol 2011;164:291–300.
  • Sachan M, Srivastava A, Ranjan R, et al. Opportunities and challenges for host-directed therapies in tuberculosis. Curr Pharm Des 2016;22:2599–604.
  • Gupta A, Misra A, Deretic V. Targeted pulmonary delivery of inducers of host macrophage autophagy as a potential host-directed chemotherapy of tuberculosis. Adv Drug Deliv Rev 2016;102:10–20.
  • Gupta A, Sharma D, Meena J, et al. Preparation and preclinical evaluation of inhalable particles containing rapamycin and anti-tuberculosis agents for induction of autophagy. Pharm Res 2016;33:1899–912.
  • Giovagnoli S, Marenzoni ML, Nocchetti M, et al. Synthesis, characterization and in vitro extra- and intracellular activity against Mycobacterium tuberculosis infection of new second-line antitubercular drug-palladium complexes. J Pharm Pharmacol 2014;66:106–21.
  • Schoubben A, Blasi P, Marenzoni ML, et al. Capreomycin supergenerics for pulmonary tuberculosis treatment: preparation, in vitro, and in vivo characterization. Eur J Pharm Biopharm 2013;83:388–95.
  • Schoubben A, Giovagnoli S, Tiralti MC, et al. Capreomycin inhalable powders prepared with an innovative spray-drying technique. Int J Pharm 2013;469:132–9.
  • Palazzo F, Giovagnoli S, Schoubben A, et al. Development of a spray-drying method for the formulation of respirable microparticles containing ofloxacin-palladium complex. Int J Pharm 2013;440:273–82.
  • Giovagnoli S, Palazzo F, Di Michele A, et al. The influence of feedstock and process variables on the encapsulation of drug suspensions by spray-drying in fast drying regime: the case of novel antitubercular drug-palladium complex containing polymeric microparticles. J Pharm Sci 2014;103:1255–68.
  • Piccaro G, Giannoni F, Filippini P, et al. Activities of drug combinations against Mycobacterium tuberculosis grown in aerobic and hypoxic acidic conditions. Antimicrob Agents Chemother 2013;57:1428–33.
  • Piccaro G, Poce G, Biava M, et al. Activity of lipophilic and hydrophilic drugs against dormant and replicating Mycobacterium tuberculosis. J Antibiot 2015;68:711–14.
  • Giovagnoli S, Schoubben A, Rossi C. Ion pairs for controlling drug delivery. In: Hickey AJ, Misra A, Fourie BP, eds. Delivery systems for tuberculosis prevention and treatment. Chichester, UK: Wiley&Sons Ltd; 2016:239–57.
  • Yokota S, Miki K. Effects of INH (Isoniazid) inhalation in patients with endobronchial tuberculosis (EBTB). Kekkaku 1999;74:873–7.
  • Tsurutani J, Sohda H, Oka M, et al. A case of multidrug-resistant pulmonary tuberculosis. Nihon Kokyuki Gakkai Zasshi 2000;38:594–8.
  • Parola P, Brouqui P. Clinical and microbiological efficacy of adjunctive salvage therapy with inhaled aminoglycosides in a patient with refractory cavitary pulmonary tuberculosis. Clin Infect Dis 2001;33:1439.
  • Rikimaru T, Koga T, Sueyasu Y, et al. Treatment of ulcerative endobronchial tuberculosis and bronchial stenosis with aerosolized streptomycin and steroids. Int J Tuberc Lung Dis 2001;5:769–74.
  • Dharmadhikari AS, Kabadi M, Gerety B, et al. Phase I, single-dose, dose-escalating study of inhaled dry powder capreomycin: a new approach to therapy of drug-resistant tuberculosis. Antimicrob Agents Chemother 2013;57:2613–19.
  • Garcia-Contreras L, Fiegel J, Telko MJ, et al. Inhaled large porous particles of capreomycin for treatment of tuberculosis in a guinea pig model. Antimicrob Agents Chemother 2007;51:2830–6.
  • Fiegel J, Garcia-Contreras L, Thomas M, et al. Preparation and in vivo evaluation of a dry powder for inhalation of capreomycin. Pharm Res 2008;25:805–11.
  • Garcia-Contreras L, Muttil P, Fallon JK, et al. Pharmacokinetics of sequential doses of capreomycin powder for inhalation in guinea pigs. Antimicrob Agents Chemother 2012;56:2612–18.
  • Hanif SNM, Garcia-Contreras L. Pharmaceutical aerosols for the treatment and prevention of tuberculosis. Front Cell Infect Microbiol 2012;2:118.
  • Ottenhoff THM, Kaufmann SHE. Vaccines against tuberculosis: where are we and where do we need to go? PLoS Pathog 2012;8:e1002607.
  • Montagnani C, Chiappini E, Galli L, de Martino M. Vaccine against tuberculosis: what’s new? BMC Infect Dis 2014;14(Suppl 1):S2.
  • Gröschel MI, Prabowo SA, Cardona PJ, et al. Therapeutic vaccines for tuberculosis: a systematic review. Vaccine 2014;32:3162–8.
  • Sou T, Meeusen EN, de Veer M, et al. New developments in dry powder pulmonary vaccine delivery. Trends Biotech 2011;29:191–8.
  • Garcia Contreras L, Awashthi S, Hanif SNM, Hickey AJ. Inhaled vaccines for the prevention of tuberculosis. J Mycobac Dis 2012;S1:002.
  • Principi N, Esposito S. The present and future of tuberculosis vaccinations. Tuberculosis 2015;95:6–13.
  • Lai R, Afkhami S, Haddadi S, et al. Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation determined T-cell homing to restricted lung mucosal compartments. Eur Respir Rev 2015;24:356–60.
  • Satti I, Meyer J, Harris SA, et al. Safety and immunogenicity of a candidate tuberculosis vaccine MVA85A delivered by aerosol in BCG-vaccinated healthy adults: a phase 1, double-blind, randomised controlled trial. Lancet Infect Dis 2014;14:939–46.
  • Zhou Q, Tanga P, Leung SSY, et al. Emerging inhalation aerosol devices and strategies: where are we headed? Adv Drug Deliv Rev 2014;75:3–17.
  • Hoppentocht M, Hagedoorn P, Frijlink HW, de Boer AH. Technological and practical challenges of dry powder inhalers and formulations. Adv Drug Deliv Rev 2014;75:18–31.
  • Healy AM, Amaro MI, Paluch KJ, Tajber L. Dry powders for oral inhalation free of lactose carrier particles. Adv Drug Deliv Rev 2014;75:32–52.
  • Varghese Vadakkan M, Vinod Kumar GS. Advancements in devices and particle engineering in dry powder inhalation technology. Curr Topics Med Chem 2016;16:1990–2008.
  • Tiddens HAWM, Bos AC, Mouton JW, et al. Inhaled antibiotics: dry or wet? Eur Respir J 2014;44:1308–18.
  • Hussain M, Madl P, Khan A. Lung deposition predictions of airborne particles and the emergence of contemporary diseases Part-I. The Health 2011;2:51–9.
  • Sethi T, Agrawal A. Structure and function of the tuberculous lung: considerations for inhaled therapies. Tuberculosis 2011;91:67–70.
  • Darquenne C, Fleming JS, Katz I, et al. Bridging the gap between science and clinical efficacy: physiology, imaging, and modeling of aerosols in the lung. J Aerosol Med Pulm Drug Deliv 2016;29:1–20.
  • Yadav AB, Singh AK, Verma RK, et al. The devil’s advocacy: when and why inhaled therapies for tuberculosis may not work. Tuberculosis 2011;91:65–6.
  • Robertson HT, Glenny RW, Stanford D, et al. High-resolution maps of regional ventilation utilizing inhaled fluorescent microspheres. J Appl Physiol 1997;82:943–53.
  • Miyawaki S, Tawhai MH, Hoffman EA, Lin CL. Effect of carrier gas properties on aerosol distribution in a CT-based human airway numerical model. Ann Biomed Eng 2012;40:1495–507.
  • Chan TL, Lippmann M. Experimental measurement and empirical modeling of the regional deposition of inhaled particles in humans. Am Ind Hyg Assoc J 1980;41:399–409.
  • Darquenne C, van Ertbruggen C, Prisk GK. Convective flow dominates aerosol delivery to the lung segments. J Appl Physiol 2011;111:48–54.
  • de Vasconcelos TF, Sapoval B, Andrade JS, et al. Particle capture into the lung made simple? J Appl Physiol 2011;110:1664–73.
  • Kim CS, Hu SC, DeWitt P, Gerrity TR. Assessment of regional deposition of inhaled particles in human lungs by serial bolus delivery method. J Appl Physiol 1996;81:2203–13.
  • Condos R, Hull FP, Schluger NW, et al. Regional deposition of aerosolized interferon-γ in pulmonary tuberculosis. Chest 2004;125:2146–55.
  • Diaz KT, Skaria S, Harris K, et al. Delivery and safety of inhaled interferon-γ in idiopathic pulmonary fibrosis. J Aerosol Med Pulm Drug Deliv 2012;25:79–87.
  • van Aalderen WM, Garcia-Marcos L, Gappa M, et al. How to match the optimal currently available inhaler device to an individual child with asthma or recurrent wheeze. Prim Care Resp Med 2015;25:14088.
  • Smith AL. Inhaled antibiotic therapy: what drug? What dose? What regimen? What formulation? J Cys Fibr 2002;1:S189–S93.
  • Dimopoulos GT, Kollef M, Matthaiou DK, et al. Aerolized antibiotics for the treatment of ventilator associated pneumonia: a new era! Pneumon 2014;27:87–93.
  • Simoens S. Factors affecting the cost effectiveness of antibiotics. Chemother Res Practice 2011;2011:249867.
  • Ott SR, Hauptmeier BM, Ernen C, et al. Treatment failure in pneumonia: impact of antibiotic treatment and cost analysis. Eur Respir J 2012;39:611–18.
  • Floyd K, Hutubessy R, Kliiman K, et al. Cost and cost-effectiveness of multidrugresistant tuberculosis treatment in Estonia and Russia. Eur Respir J 2012;40:133–42.
  • Fitzpatrick C, Floyd K. A systematic review of the cost and cost effectiveness of treatment for multidrug-resistant tuberculosis. Pharmacoeconomics 2012;30:63–80.
  • Bassili A, Fitzpatrick C, Qadeer E, et al. A systematic review of the effectiveness of hospital and ambulatory-based management of multidrug-resistant tuberculosis. Am J Trop Med Hyg 2013;89:271–80.
  • Azadi M, Bishai DM, Dowdy DW, et al. Cost-effectiveness of tuberculosis screening and isoniazid treatment in the TB/HIV in Rio (THRio) Study. Int J Tuberc Lung Dis 2014;18:1443–8.
  • Diel R, Hittel N, Schaberg T. Cost effectiveness of treating multi-drug resistant tuberculosis by adding DeltybaTM to background regimens in Germany. Resp Med 2015;109:632–41.
  • WHO/HTM/TB/2006.361. 2006. Guidelines for the programmatic management of drug-resistant tuberculosis. Available from: http://www.stoptb.org/assets/documents/resources/publications/technical/tb_guidelines.pdf
  • WHO/HTM/TB/2011.6. 2011. Guidelines for the programmatic management of drug-resistant tuberculosis- 2011 update. Available from: http://apps.who.int/iris/bitstream/10665/44597/1/9789241501583_eng.pdf
  • Tappenden P, Harnan S, Uttley L, et al. The cost effectiveness of dry powder antibiotics for the treatment of Pseudomonas aeruginosa in patients with cystic fibrosis. PharmacoEconomics 2014;32:159–72.
  • Gauthier TP, Wasko J, Unger NR, et al. Cost reduction of inhaled tobramycin by use of preservative-free intravenous tobramycin given via inhalation. Antibiotics 2016;5:2.
  • Martin RJ, Price D, Roche N, et al. Cost-effectiveness of initiating extrafine- or standard size-particle inhaled corticosteroid for asthma in two health-care systems: a retrospective matched cohort study. Npj Prim Care Resp Med 2014;24:14081.
  • Yang JW, Fan LC, Lu HW, et al. Efficacy and safety of long-term inhaled antibiotic for patients with noncystic fibrosis bronchiectasis: a meta-analysis. Clin Respir J 2016;10:731–9.
  • US FDA Guidance for Industry. 1998. Metered dose inhaler (MDI) and dry powder inhaler (DPI) drug products: chemistry, manufacturing and controls documentation: Center for Drug Evaluation and Research, Rockville, MD, docket 98D-0997. Available from: http://www.US FDA.gov/downloads/Drugs/…/Guidances/ucm070573.pdf
  • EMEA/CHMP/QWP/49313/2005 Corr. 2006. Committee for medicinal products for human use. Guideline on the pharmaceutical quality of inhalation and nasal products. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003568.pdf
  • US FDA Guidance for Industry. 2002. Nasal spray and inhalation solution, suspension, and spray drug products- chemistry, manufacturing, and controls documentation. Available from: http://www.US FDA.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm070575.pdf
  • CPMP/EWP/4151/00 Rev. 1. 2009. Committee for medicinal products for human use. guideline on the requirements for clinical documentation for Orally Inhaled Products (OIP) including the requirements for demonstration of therapeutic equivalence between two inhaled products for use in the treatment of asthma and Chronic Obstructive Pulmonary Disease (COPD) in adults and for use in the treatment of asthma in children and adolescents. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003504.pdf
  • US FDA. 2013. Draft guidance on fluticasone propionate; salmeterol xinafoate. Available from: http://www.US FDA.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm367643.pdf
  • US FDA. 2015. Draft guidance on ipratropium bromide. Available from: http://www.US FDA.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm436831.pdf
  • US FDA. 2015. Draft guidance on levalbuterol tartrate. Available from: http://www.US FDA.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm452780.pdf
  • US FDA. 2015. Draft guidance on budesonide; formoterol fumarate dehydrate. Available from: http://www.US FDA.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm452690.pdf
  • Hou S, Wu J, Li X, Shu H. Practical, regulatory and clinical considerations for development of inhalation drug products. Asian J Pharm Sci 2015;10:490–500.
  • Al-Numani D, Colucci P, Ducharme MP. Rethinking bioequivalence and equivalence requirements of orally inhaled drug products. Asian J Pharm Sci 2015;10:461–71.
  • Lee SL, Saluja B, García-Arieta A, et al. Regulatory considerations for approval of generic inhalation drug products in the US, EU, Brazil, China, and India. AAPS J 2015;17:1285–304.
  • Holt J, Hickey AJ, Sandell D. From Q2 to QbD: the influence of formulation changes on MDI performance. RDDAsia 2014;1:33–43.
  • McShane H, Williams A. A review of preclinical animal models utilised for TB vaccine evaluation in the context of recent human efficacy data. Tuberculosis 2014;94:105–10.
  • De Groote MA, Gilliland JC, Wells CL, et al. Comparative studies evaluating mouse models used for efficacy testing of experimental drugs against Mycobacterium tuberculosis. Antimicrob Agents Chemother 2011;55:1237–47.
  • Calderon VE, Valbuena G, Goez Y, et al. A humanized mouse model of tuberculosis. PLoS One 2013;8:e63331.
  • Konstan MW, Flume PA, Kappler M, et al. Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: the EAGER trial. J Cyst Fibros 2011;10:54–61.
  • Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med 1999;340:23–30.
  • EMEA/CHMP/EWP/9147/2008-corr*. 2009. Guidelines for development of drugs for cystic fibrosis. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/12/WC500017055.pdf
  • US FDA. Workshop- Issues in the design of clinical trials of aerosolized antimicrobials for the treatment of cystic fibrosis. September 23-24, 2010, Silver Spring, Maryland, US. Available from: http://www.US FDA.gov/downloads/Drugs/NewsEvents/UCM231055.pdf+endpoints+CF+transcripts&client=US FDAgov&lr=&proxystylesheet=US FDAgov&output=xml_no_dtd&ie=UTF8&site=US FDAgov&access=p&oe=UTF-8
  • US FDA Guidance for Industry. 2009. Patient-reported outcome measures: use in medical product development to support labeling claims. Available from: http://www.US FDA.gov/downloads/Drugs/…/Guidances/UCM193282.pdf
  • Montgomery AB, Abuan T, Yeager MA. Regulatory aspects of phase 3 endpoints for new inhaled antibiotics for cystic fibrosis patients with chronic Pseudomonas aeruginosa infections. J Aerosol Med Pulm Drug Deliv 2012;25:198–203.
  • Mukker JK, Singh RSP, Derendorf H. Pharmacokinetic and pharmacodynamic implications in inhalable antimicrobial therapy. Adv Drug Deliv Rev 2015;85:57–64.
  • Wallis RS. Mathematical models of tuberculosis reactivation and relapse. Front Microbiol 2016;7:669.
  • Panzitta M, Bruno G, Giovagnoli S, et al. Drug delivery system innovation and health technology assessment: upgrading from clinical to technological assessment. Int J Pharm 2015;495:1005–18.
  • Cardona PJ. Ten questions to challenge the natural history of tuberculosis. In: Cardona PJ, ed. Understanding tuberculosis: analyzing the origin of Mycobacterium tuberculosis pathogenicity. InTech; 2012:3–16. Available from: http://www.intechopen.com/books/understanding-tuberculosis-analyzing-the-origin-of-mycobacterium-tuberculosis-pathogenicity/ten-questions-to-challenge-the-natural-history-of-tuberculosis
  • Cannas A, Mazzarelli A, Di Caro A, et al. Molecular typing of Mycobacterium tuberculosis strains: a fundamental tool for tuberculosis control and elimination. Infect Dis Rep 2016;8:6567.
  • Lenaerts A, Barry CE, III., Dartois V. Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses. Immunol Rev 2015;264:288–307.
  • Hawn TR, Matheson AI, Maley SN, Vandal O. Host-directed therapeutics for tuberculosis: can we harness the host? Microbiol Mol Biol Rev 2013;77:608–27.
  • Wallis RS, Hafner R. Advancing host-directed therapy for tuberculosis. Nat Rev Immunol 2015;15:255–63.
  • Zumla A, Maeurer M. Host-Directed Therapies Network (HDT-NET) Consortium. Host-directed therapies for tackling multi-drug resistant tuberculosis: learning from the Pasteur-Bechamp debates. Clin Infect Dis 2015;61:1432–8.
  • Bao Z, Chen R, Zhang P, et al. A potential target gene for the host-directed therapy of mycobacterial infection in murine macrophages. Int J Mol Med 2016;38:823–33.
  • Kiran D, Podell BK, Chambers M, Basaraba RJ. Host-directed therapy targeting the Mycobacterium tuberculosis granuloma: a review. Semin Immunopathol 2016;38:167–83.
  • Zumla A, Rao M, Dodoo E, Maeurer M. Potential of immunomodulatory agents as adjunct host-directed therapies for multidrug-resistant tuberculosis. BMC Med 2016;14:89.
  • Wallis RS, Maeurer M, Mwaba P, et al. Tuberculosis–advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers. Lancet Infect Dis 2016;16:e34–46.
  • Guzman JD, Evangelopoulos D, Gupta A, et al. Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HT-SPOTi wholecell phenotypic assay. BMJ Open 2013;3:e002672.
  • Vilaplana C, Marzo E, Tapia G, et al. Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis. J Infect Dis 2013;208:199–202.
  • Lowe DM, Redford PS, Wilkinson RJ, et al. Neutrophils in tuberculosis: friend or foe? Trends Immunol 2012;33:14–25.
  • Millet J-P, Shaw E, Orcau A, et al. Tuberculosis recurrence after completion treatment in a European city: reinfection or relapse? PLoS One 2013;8:e64898.
  • Cacho J, Perez Meixeira A, Cano I, et al. Recurrent tuberculosis from 1992 to 2004 in a metropolitan area. Eur Respir J 2007;30:333–7.
  • Botero LE, Delgado-Serrano L, Cepeda ML, et al. Respiratory tract clinical sample selection for microbiota analysis in patients with pulmonary tuberculosis. Microbiome 2014;2:29.
  • Adami AJ, Cervantes JL. The microbiome at the pulmonary alveolar niche and its role in Mycobacterium tuberculosis infection. Tuberculosis 2015;95:651–8.
  • Wu J, Liu W, He L, et al. Sputum microbiota associated with new, recurrent and treatment failure tuberculosis. PLoS One 2013;8:e83445.
  • Crepeta A, Repetto E, Rousana AA, et al. Lessons learnt from TB screening in closed immigration centres in Italy. Int Health 2016;8:324–9.
  • Sañé Schepisi M, Gualano G, Piselli P, et al. Active tuberculosis case finding interventions among immigrants, refugees and asylum seekers in Italy. Infect Dis Rep 2016;8:6594.
  • Ghafoor A, Mehraj J, Afridi ND, et al. Multidrug resistant Mycobacterium tuberculosis amongst Category I & II failures and Category II relapse patients from Pakistan. Int J Mycobact 2012;1:118–23.
  • Caminero JA, ed. Guidelines for clinical and operational management of drug-resistant tuberculosis. Paris, France: International Union Against Tuberculosis and Lung Disease; 2013.
  • Renwick MJ, Brogan DM, Mossialos E. A systematic review and critical assessment of incentive strategies for discovery and development of novel antibiotics. J Antibiotics 2016;69:73–88.
  • Renwick MJ, Simpkin V, Mossialos E. International and European initiatives targeting innovation in antibiotic drug discovery and development- the need for a one health - one Europe - one world framework. 2016 Report on Antibiotic RD Initiatives; 2016. Available from: https://english.eu2016.nl/documents/reports/2016/02/10/2016-report-on-antibiotic-rd-initiatives
  • Fourie PB, Nettey OS. Inhaled therapies for tuberculosis: a viable approach for spray-dried drugs delivered by handheld dry powder inhaler. Inhalation; 2015 February: 5–10. Available from: http://www.inhalationmag.com/Content/getArticle.aspx?ItemID=45ef3fc5-c9b4-441f-91db-ba35ee497957

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.