You are here

Technological and behavioral strategies to reduce treatment burden and improve adherence to inhaled antibiotics in cystic fibrosis

Respiratory Medicine, pages S24 - S31

Summary

Aerosolized antibiotics are a common treatment option for patients with cystic fibrosis and chronic airway infection, as high doses can be delivered topically to the site of the infection while systemic exposure is minimized. Patients also use other aerosolized therapies (e.g. mucus-active agents, airway-wetting agents, and bronchodilators), adding significantly increase timed and complexity to their daily regimen, and often leading to lower adherence rates. A number of novel technological strategies are available that may reduce dose frequency and increase the speed of drug delivery. Psychologically based therapies may also be used to help modify behavior and thus improve adherence to treatment. Clinicians need to explore both technological and psychological strategies that will assist in the successful maintenance of treatment requirements.

Keywords: Cystic fibrosis, Behavioral strategies, Technological strategies, Pseudomonas aeruginosa, Inhaled antibiotics, Pulmonary exacerbations, Treatment adherence.

References

  • 1 RL Gibson, JL Burns, BW Ramsey. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med. 2003;168:918-951 Crossref
  • 2 JJ Lipuma. The changing microbial epidemiology in cystic fibrosis. Clin Microbiol Rev. 2010;23:299-323 Crossref
  • 3 AR Hauser, M Jain, M Bar-Meir, SA McColley. Clinical significance of microbial infection and adaptation in cystic fibrosis. Clin Microbiol Rev. 2011;24:29-70
  • 4 PA Flume, BP O'Sullivan, KA Robinson, et al. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2007;176:957-969 Crossref
  • 5 H Heijerman, E Westerman, S Conway, D Touw, G Doring, consensus working group. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: a European consensus. J Cyst Fibros. 2009;8:295-315 Crossref
  • 6 SM Moskowitz, SJ Silva, N Mayer-Hamblett, et al. Shifting patterns of inhaled antibiotic use in cystic fibrosis. Pediatr Pulmonol. 2008;43:874-881 Crossref
  • 7 DE Geller. Aerosol antibiotics in cystic fibrosis. Respir Care. 2009;54:658-670 Crossref
  • 8 GS Sawicki, DE Sellers, WM Robinson. High treatment burden in adults with cystic fibrosis: challenges to disease self-management. J Cyst Fibros. 2009;8:91-96 Crossref
  • 9 MR DiMatteo. Variations in patients' adherence to medical recommendations: a quantitative review of 50 years of research. Med Care. 2004;42:200-209 Crossref
  • 10 RP Arias Llorente, C Bousoño García, JJ Díaz Martín. Treatment compliance in children and adults with cystic fibrosis. J Cyst Fibros. 2008;7:359-367 Crossref
  • 11 DR Czajkowski, GP Koocher. Medical compliance and coping with cystic fibrosis. J Child Psychol Psychiatry. 1987;28:311-319 Crossref
  • 12 LJ Kettler, SM Sawyer, HR Winefield, HW Greville. Determinants of adherence in adults with CF. Thorax. 2002;57:459-464 Crossref
  • 13 MN Eakin, A Bilderback, MP Boyle, PJ Mogayzel, KA Riekert. Longitudinal association between medication adherence and lung health in people with cystic fibrosis. J Cyst Fibros. 2011;10:258-264 Crossref
  • 14 JL Rau. Determinants of patient adherence to an aerosol regimen. Respir Care. 2005;50:1346-1359
  • 15 H Milgrom, B Bender, L Ackerson, P Bowry, B Smith, C Rand. Noncompliance and treatment failure in children with asthma. J Allergy Clin Immunol. 1996;98:1051-1057 Crossref
  • 16 BA Briesacher, AL Quittner, L Saiman, P Sacco, H Fouayzi, LM Quittell. Adherence with tobramycin inhaled solution and health care utilization. BMC Pulm Med. 2011;11:5 Crossref
  • 17 KC Kesser, DE Geller. New aerosol delivery devices for cystic fibrosis. Respir Care. 2009;54:754-767
  • 18 DE Geller. The science of aerosol delivery in cystic fibrosis. Pediatr Pulmonol. 2008;43(9 SupplA):S5-17
  • 19 PM Mendelman, AL Smith, J Levy, A Weber, B Ramsey, RL Davis. Aminoglycoside penetration, inactivation, and efficacy in cystic fibrosis sputum. Am Rev Respir Dis. 1985;132:761-765
  • 20 P King, O Lomovskaya, DC Griffith, JL Burns, MN Dudley. In vitro pharmacodynamics of levofloxacin and other aerosolized antibiotics under multiple conditions relevant to chronic pulmonary infection in cystic fibrosis. Antimicrob Agents Chemother. 2010;54:143-148 Crossref
  • 21 BW Ramsey, HL Dorkin, JD Eisenberg, et al. Efficacy of aerosolized tobramycin in patients with cystic fibrosis. N Engl J Med. 1993;328:1740-1746 Crossref
  • 22 A Chuchalin, E Csiszér, K Gyurkovics, et al. A formulation of aerosolized tobramycin (Bramitob) in the treatment of patients with cystic fibrosis and Pseudomonas aeruginosa infection: a double-blind, placebo-controlled, multicenter study. Paediatr Drugs. 2007;9(Suppl 1):21-31 Crossref
  • 23 AL Coates, M Green, K Leung, et al. Rapid pulmonary delivery of inhaled tobramycin for Pseudomonas infection in cystic fibrosis. Pediatr Pulmonol. 2008;4:753-759 Crossref
  • 24 L Dupont, P Minic, S Fustik, et al. A randomized, placebo-controlled study of nebulized liposomal amikacin (Arikace) in the treatment of cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection. J Cyst Fibros. 2008;7(Suppl 2):S26 Abstract 102. Crossref
  • 25 OO Okusanya, SM Bhavnani, J Hammel, et al. Pharmacokinetic and pharmacodynamic evaluation of liposomal amikacin for inhalation in cystic fibrosis patients with chronic pseudomonal infection. Antimicrob Agents Chemother. 2009;53:3847-3854 Crossref
  • 26 P Bruinenberg, B Otulana, J Blanchard, et al. The effect of once-a-day inhaled liposomal ciprofloxacin hydrochloride on sputum bacterial density in cystic fibrosis patients with chronic pulmonary P. aeruginosa colonization. Pediatr Pulmonol. 2008;43(Suppl 31):344 Abstract 401.
  • 27 EM Westerman, AH De Boer, PPH Le Brun, et al. Dry powder inhalation of colistin in cystic fibrosis patients: a single dose pilot study. J Cyst Fibros. 2007;6:284-292 Crossref
  • 28 DE Geller, J Weers, S Heuerding. Development of an inhaled dry-powder formulation of tobramycin using PulmoSphere(tm) technology. J Aerosol Med Pulm Drug Deliv. 2011;24:175-182 Crossref
  • 29 MT Newhouse, PH Hirst, SP Duddu, et al. Inhalation of a dry powder tobramycin PulmoSphere formulation in healthy volunteers. Chest. 2003;124:360-366 Crossref
  • 30 DE Geller, M Konstan, J Smith, S Noonberg, C Conrad. A novel tobramycin inhalation powder in cystic fibrosis subjects: pharmacokinetics and safety. Pediatr Pulmonol. 2007;42:307-313 Crossref
  • 31 MW Konstan, DE Geller, P Minic, F Brockhaus, J Zhang, G Angyalosi. Tobramycin inhalation powder for Pseudomonas aeruginosa infection in cystic fibrosis: the EVOLVE trial. Pediatr Pulmonol. 2011;46:230-238 Crossref
  • 32 MW Konstan, PA Flume, M Kappler, et al. Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: the EAGER trial. J Cyst Fibros. 2011;10:54-61 Crossref
  • 33 H Stass, S Baumann-Noss, H Delesen, et al. Pharmacokinetics of ciprofloxacin PulmoSphere® inhalational powder. J Cyst Fibros. 2008;7(Suppl 2):S26 Abstract 103. Crossref
  • 34 HA Tiddens, DE Geller, P Challoner, et al. Effect of dry powder inhaler resistance on the inspiratory flow rates and volumes of cystic fibrosis patients of six years and older. J Aerosol Med. 2006;19:456-465 Crossref
  • 35 BC Trapnell, SA McColley, DG Kissner, et al. Fosfomycin/tobramycin for inhalation in cystic fibrosis patients with Pseudomonas airway infection. Am J Respir Crit Care Med. 2011; (in press).
  • 36 Y Yang, MD Tsifansky, CJ Wu, HI Yang, G Schmidt, Y Yeo. Inhalable antibiotic delivery using a dry powder co-delivering recombinant deoxyribonuclease and ciprofloxacin for treatment of cystic fibrosis. Pharm Res. 2010;27:151-160 Crossref
  • 37 RL Gibson, GZ Retsch-Bogart, C Oermann, et al. Microbiology, safety, and pharmacokinetics of aztreonam lysinate for inhalation in patients with cystic fibrosis. Pediatr Pulmonol. 2006;41:656-665 Crossref
  • 38 DE Geller, PA Flume, D Staab, R Fischer, JS Loutit, DJ Conrad. Levofloxacin inhalation solution (MP-376) in patients with cystic fibrosis with Pseudomonas aeruginosa. Am J Respir Crit Care Med. 2011;183:1510-1516 Crossref
  • 39 D Hubert, S Leroy, R Nove-Josserand, et al. Pharmacokinetics and safety of tobramycin administered by the PARI eFlow® rapid nebulizer in cystic fibrosis. J Cyst Fibros. 2009;8:332-337 Crossref
  • 40 W Lenney, F Edenborough, P Kho, JM Kovarik. Lung deposition of inhaled tobramycin with eFlow rapid/LC Plus jet nebuliser in healthy and cystic fibrosis subjects. J Cyst Fibros. 2011;10:9-14 Crossref
  • 41 J Denyer, T Dyche. The Adaptive Aerosol Delivery (AAD) technology: past, present, and future. J Aerosol Med Pulm Drug Deliv. 2010;23(Suppl 1):S1-10
  • 42 P Brand, I Friemel, T Meyer, J Schulz, K Haussinger. Total deposition of therapeutic particles during spontaneous and controlled inhalations. J Pharm Sci. 2000;89:724-731 Crossref
  • 43 P McCormack, PS McNamara, KW Southern. A randomised controlled trial of breathing modes for adaptive aerosol delivery in children with cystic fibrosis. J Cyst Fibros. 2011;10:343-349 Crossref
  • 44 WD Bennett. Controlled inhalation of aerosolized therapeutics. Expert Opin Drug Deliv. 2005;2:763-767 Crossref
  • 45 J Denyer. Adherence monitoring in drug delivery. Expert Opin Drug Deliv. 2010;7:1127-1131 Crossref
  • 46 Cystic Fibrosis Trust. Antibiotic treatment for cystic fibrosis, 3rd edn. Report of the UK Cystic Fibrosis Trust Antibiotic Working Group; 2009.
  • 47 PS McNamara, P McCormack, AJ McDonald, L Heaf, KW Southern. Open adherence monitoring using routine data download from an adaptive aerosol delivery nebuliser in children with cystic fibrosis. J Cyst Fibros. 2009;8:258-263 Crossref
  • 48 D Meichenbaum, DC Turk. Facilitating Treatment Adherence: A Practitioner's Guidebook (Plenum Press, New York, 1987)
  • 49 C Gibson. Perspective in parental coping with a chronically ill child: the case of cystic fibrosis. Issues Compr Pediatr Nurs. 1988;11:33-41 Crossref
  • 50 S Madge. 'Challenges for nurses'. A Bush, EWFW Alton, JC Davies, U Griesenbach, A Jaffe (Eds.) in: Cystic Fibrosis in the 21st Century. Progress in Respiratory Research. vol. 34 (Karger, Basel, Switzerland, 2006) 286-292
  • 51 EJ Burker, J Sedway, S Carone. Psychological and educational factors: better predictors of work status than FEV1 in adults with CF. Pediatr Pulmonol. 2004;38:413-418 Crossref
  • 52 J Moise, D Drotar, C Doershuk, RC Stern. Correlates of psychosocial adjustment among young adults with cystic fibrosis. J Dev Behav Pediatr. 1987;8:141-148
  • 53 H Oxley, AK Webb. How a clinical psychologist manages the problems of adults with cystic fibrosis. J R Soc Med. 2005;98(Suppl 45):37-46
  • 54 J Hafetz, VA Miller. Child and parent perceptions of monitoring in chronic illness management: a qualitative study. Child Care Health Dev. 2010;36:655-662 Crossref
  • 55 EJ Dziuban, L Saab-Abazeed, SR Chaudhry, DS Streetman, SZ Nasr. Identifying barriers to treatment adherence and related attitudinal patterns in adolescents with cystic fibrosis. Pediatr Pulmonol. 2010;45:450-458 Crossref
  • 56 E Lehane, G McCarthy. Intentional and unintentional medication non-adherence: a comprehensive framework for clinical research and practice? A discussion paper. Int J Nurs Stud. 2007;44:1468-1477 Crossref
  • 57 AC Modi, AL Quittner. Barriers to treatment adherence for children with cystic fibrosis and asthma: what gets in the way?. J Pediatr Psychol. 2006;31:846-858
  • 58 J Abbott, M Dodd, AK Webb. Different perceptions of disease severity and self care between patients with cystic fibrosis, their close companions, and physician. Thorax. 1995;50:794-796 Crossref
  • 59 AJA Duff, GJ Latchford. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: poor adherence and the need to address it. J Cyst Fibros. 2010;9:455-456 Crossref
  • 60 B Bender, H Milgrom, A Apter. Adherence intervention research: what have we learned and what do we do next?. J Allergy Clin Immunol. 2003;112:489-494 Crossref
  • 61 B Bender, FS Wamboldt, SL O'Connor, et al. Measurement of children's asthma medication adherence by self report, mother report, canister weight, and Doser CT. Ann Allergy Asthma Immunol. 2000;85:416-421 Crossref
  • 62 T Daniels, L Goodacre, C Sutton, K Pollard, S Conway, D Peckham. Accurate assessment of adherence: self-report and clinician report vs electronic monitoring of nebulizers. Chest. 2011;140:425-432 Crossref
  • 63 RA Elliott, N Barber, R Horne. Cost-effectiveness of adherence-enhancing interventions: a quality assessment of the evidence. Ann Pharmacother. 2005;39:508-515 Crossref
  • 64 LM McClimans, M Dunn, AM Slowther. Health policy, patient-centred care and clinical ethics. J Eval Clin Pract. 2011;17:913-919 Crossref
  • 65 AJA Duff, GJ Latchford. Motivational interviewing for adherence problems in cystic fibrosis: state of the art review. Pediatr Pulmonol. 2010;45:211-220
  • 66 LM Hides, KS Elkins, A Scaffidi, SM Cotton, S Carroll, DI Lubman. Does the addition of integrated cognitive behaviour therapy and motivational interviewing improve the outcomes of standard care for young people with comorbid depression and substance misuse?. Med J Aust. 2011;195:S31-S37
  • 67 D Fowler, R Rollinson, P French. Adherence and competence assessment in studies of CBT for psychosis: current status and future directions. Epidemiol Psychiatr Sci. 2011;20:121-126 Crossref
  • 68 PR Brocklehurst. Personal construct psychology: a theory to help understand professional development, a philosophy to support it. Prim Dent Care. 2010;17:179-187 Crossref
  • 69 AM Nezu, CM Nezu, MG Perri. Problem solving to promote treatment adherence. WT O'Donohue, ER Levensky (Eds.) Promoting Treatment Adherence: A Practical Handbook for Health Care Providers (Sage Publications, Inc, New York, 2006) 135-148 Crossref
  • 70 BM Melnyk, NF Feinstein, Z Moldenhouer, L Small. Coping in parents of children who are chronically ill: strategies for assessment and intervention. Pediatr Nurs. 2001;27:547-558

Footnotes

a Nemours Children's Clinic, Orlando, Florida, USA

b Royal Brompton Hospital, London, England, UK

* Corresponding author. David E. Geller, MD. Director, Aerosol Research Lab & CF Center, Nemours Children's Clinic, 496 S Delaney Avenue, #406A, Orlando, FL 3280, USA. Tel.: +1 407 650 7715; fax: +1 407 650 7124