Skip to main content
SpringerLink
Log in

Tiotropium Respimat Soft Mist Inhaler versus HandiHaler to improve sleeping oxygen saturation and sleep quality in COPD

  • Sleep Breathing Physiology and Disorders • Original Article
  • Published:
Sleep and Breathing Aims and scope Submit manuscript

Abstract

Purpose

Patients with chronic obstructive pulmonary disease (COPD) have poor sleep quality as a result of various alterations in oxygenation parameters and sleep macro- and micro-architecture. There is a shortage of data to support the efficacy of long-acting inhaled anticholinergic agents in improving these adverse effects, which are known to have a negative impact on clinical outcomes. We aimed to compare the tiotropium Respimat Soft Mist Inhaler and the HandiHaler in terms of their effects on sleeping oxygen saturation (SaO2) and sleep quality in patients with COPD.

Methods

In a randomized, open-label, parallel-group trial involving 200 patients with mild to moderate COPD (resting arterial oxygen tension >60 mmHg while awake), we compared the effects of 6 months’ treatment with the two devices on sleeping SaO2 and sleep quality. Overnight polysomnography and pulmonary function testing were performed at baseline and after 6 months’ treatment.

Results

A total of 188 patients completed the trial. Both groups showed significant improvement in minimum sleep SaO2 and time of sleep spent with SaO2 below 90 (TST90) compared to baseline. The patients using the Respimat had significantly better TST90 than did those using the HandiHaler. Sleep disturbance was highly variable in these patients, but the sleep stage durations were significantly better in the Respimat group.

Conclusions

Sleeping SaO2 can be improved by tiotropium delivered using either the HandiHaler device or the Respimat Soft Mist Inhaler. However, the patients who used the Respimat device had significantly better TST90 and sleep architecture parameters.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Valipour A, Lavie P, Lothaller H, Mikulic I, Burghuber OC (2011) Sleep profile and symptoms of sleep disorders in patients with stable mild to moderate chronic obstructive pulmonary disease. Sleep Med 12:367–372

    Article  PubMed  Google Scholar 

  2. Parish JM (2009) Sleep-related problems in common medical conditions. Chest 135:563–572

    Article  PubMed  Google Scholar 

  3. Marrone O, Salvaggio A, Insalaco G (2006) Respiratory disorders during sleep in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 1:363–372

    PubMed  PubMed Central  Google Scholar 

  4. Mueller PT, Gomes MD, Viegas CA, Neder JA (2008) Systemic effects of nocturnal hypoxemia in patients with chronic obstructive pulmonary disease without obstructive sleep apnoea syndrome. J Bras Pneumol 34:567–574

    Article  Google Scholar 

  5. Gilmartin GS, Tamisier R, Curley M, Weiss JW (2008) Ventilatory, hemodynamic, sympathetic nervous system, and vascular reactivity changes after recurrent nocturnal sustained hypoxia in humans. Am J Physiol Heart Circ Physiol 295:H778–H785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2013: Global strategy for the diagnosis, management and prevention of COPD. 2013. http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html. Accessed 21 January 2015

  7. Tashkin DP, Celli B, Senn S et al (2008) A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 359:1543–1554

    Article  CAS  PubMed  Google Scholar 

  8. Niewoehner DE, Rice K, Cote C, Paulson D, Cooper JA Jr, Korducki L, Cassino C, Kesten S (2005) Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann Intern Med 143:317–326

    Article  CAS  PubMed  Google Scholar 

  9. O’Donnell DE, Flüge T, Gerken F, Hamilton A, Webb K, Aguilaniu B, Make B, Magnussen H (2004) Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J 23:832–840

    Article  PubMed  Google Scholar 

  10. Tsai SC, Lee-Chiong T (2009) Lung hyperinflation and sleep quality in the overlap syndrome. COPD 6:419–420

    Article  PubMed  Google Scholar 

  11. Kwon JS, Wolfe LF, Lu BS, Kalhan R (2009) Hyperinflation is associated with lower sleep efficiency in COPD with co-existent obstructive sleep apnea. COPD 6:441–445

    Article  PubMed  Google Scholar 

  12. McNicholas WT, Calverley PM, Lee A, Edwards JC (2004) Tiotropium Sleep Study in COPD Investigators. Long-acting inhaled anticholinergic therapy improves sleeping oxygen saturation in COPD. Eur Respir J 23:825–831

    Article  CAS  PubMed  Google Scholar 

  13. Wise RA, Anzueto A, Cotton D et al (2013) Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med 369:1491–1501

    Article  CAS  PubMed  Google Scholar 

  14. Global Initiative for Chronic Obstructive Lung Disease (GOLD): Global strategy for the diagnosis, management and prevention of COPD (2013) http://www.goldcopd.org/Guidelines/guideline-2010-gold-report.html. Accessed 21 January 2015

  15. Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14:540–545

    CAS  PubMed  Google Scholar 

  16. American Thoracic Society (1995) Standardization of spirometry, 1994 update. Am J Respir Crit Care Med 152:1107–1136

    Article  Google Scholar 

  17. Iber K, Ancoli-Israel S, Chesson AL, Quan SF (2007) The AASM Manual for the scoring of sleep and associated events. American Academy of Sleep Medicine, Westchester

  18. Sanders MH, Newman AB, Haggerty CL, Redline S, Lebowitz M, Samet J, O'Connor GT, Punjabi NM, Shahar E, Sleep Heart Health Study (2003) Sleep and sleep-disordered breathing in adults with predominantly mild obstructive airway disease. Am J Respir Crit Care Med 167:7–14

    Article  PubMed  Google Scholar 

  19. Catterall JR, Douglas NJ, Calverley PM, Shapiro CM, Brezinova V, Brash HM, Flenley DC (1983) Transient hypoxemia during sleep in chronic obstructive pulmonary disease is not a sleep apnea syndrome. Am Rev Respir Dis 128:24–29

    Article  CAS  PubMed  Google Scholar 

  20. Douglas NJ (1992) Nocturnal hypoxemia in patients with chronic obstructive pulmonary disease. Clin Chest Med 13:523–532

    CAS  PubMed  Google Scholar 

  21. Postma DS, Keyzer JJ, Koëter GH, Sluiter HJ, De Vries K (1985) Influence of the parasympathetic nervous system on nocturnal bronchial obstruction. Clin Sci 69:251–258

    Article  CAS  PubMed  Google Scholar 

  22. Calverley PM, Lee A, Towse L, van Noord J, Witek TJ, Kelsen S (2003) Effect of tiotropium bromide on circadian variation in airflow limitation in chronic obstructive pulmonary disease. Thorax 58:855–860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Martin RJ, Bartelson BL, Smith P, Hudgel DW, Lewis D, Pohl G, Koker P, Souhrada JF (1999) Effect of ipratropium bromide treatment on oxygen saturation and sleep quality in COPD. Chest 115:1525–1532

    Article  Google Scholar 

  24. Sposato B, Franco C (2008) Short term effect of a single dose of formoterol or tiotropium on the isolated nocturnal hypoxemia in stable COPD patients: a double blind randomized study. Eur Rev Med Pharmacol Sci 12:203–211

    CAS  PubMed  Google Scholar 

  25. McNicholas WT (2006) Sleep in chronic obstructive pulmonary disease. Eur Respir Mon 38:325–336

    Google Scholar 

  26. Boselli M, Parrino L, Smerieri A, Terzano MG (1998) Effect of age on EEG arousals in normal sleep. Sleep 21:351–357

    CAS  PubMed  Google Scholar 

  27. Mermigkis C, Kopanakis A, Foldvary-Schaefer N, Golish J, Polychronopoulos V, Schiza S, Amfilochiou A, Siafakas N, Bouros D (2007) Health-related quality of life in patients with obstructive sleep apnoea and chronic obstructive pulmonary disease (overlap syndrome). Int J Clin Pract 61:207–211

    Article  CAS  PubMed  Google Scholar 

  28. Fleetham J, West P, Mezon B, Conway W, Roth T, Kryger M (1982) Sleep, arousals, and oxygen desaturation in chronic obstructive pulmonary disease: the effect of oxygen therapy. Am Rev Respir Dis 126:429–433

    CAS  PubMed  Google Scholar 

  29. Calverley PM, Brezinova V, Douglas NJ, Catterall JR, Flenley DC (1982) The effect of oxygenation on sleep quality in chronic bronchitis and emphysema. Am Rev Respir Dis 126:206–210

    CAS  PubMed  Google Scholar 

  30. Lewis CA, Fergusson W, Eaton T, Zeng I, Kolbe J (2009) Isolated nocturnal desaturation in COPD: prevalence and impact on quality of life and sleep. Thorax 64:133–138

    Article  CAS  PubMed  Google Scholar 

  31. McNicholas WT, Verbraecken J, Marin JM (2013) Sleep disorders in COPD: the forgotten dimension. Eur Respir Rev 22:365–375

    Article  PubMed  Google Scholar 

  32. Nunes DM, Mota RM, de Pontes Neto OL, Pereira ED, de Bruin VM, de Bruin PF (2009) Impaired sleep reduces quality of life in chronic obstructive pulmonary disease. Lung 187:159–163

    Article  PubMed  Google Scholar 

  33. Omachi TA, Blanc PD, Claman DM, Chen H, Yelin EH, Julian L, Katz PP (2012) Disturbed sleep among COPD patients is longitudinally associated with mortality and adverse COPD outcomes. Sleep Med 13:476–483

    Article  PubMed  PubMed Central  Google Scholar 

  34. Fletcher EC, Miller J, Divine GW, Fletcher JG, Miller T (1987) Nocturnal oxyhemoglobin desaturation in COPD patients with arterial oxygen tensions above 60 mm Hg. Chest 92:604–608

    Article  CAS  PubMed  Google Scholar 

  35. Dalby R, Spallek M, Voshaar T (2004) A review of the development of respimat soft mist inhaler. Int J Pharm 283:1–9

    Article  CAS  PubMed  Google Scholar 

  36. Beeh KM, Beier J, Donohue JF (2012) Clinical trial design in chronic obstructive pulmonary disease: current perspectives and considerations with regard to blinding of tiotropium. Respir Res 13:52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Author information

Authors and Affiliations

  1. Sleep Disorders Center, Department of Thoracic Medicine, University of Crete, 71110, Heraklion, Crete, Greece

    Izolde Bouloukaki, Nikolaos Tzanakis, Charalampos Mermigkis, Katerina Giannadaki, Violeta Moniaki, Eleni Mauroudi, Stylianos Michelakis & Sophia E. Schiza

Authors
  1. Izolde Bouloukaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nikolaos Tzanakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Charalampos Mermigkis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katerina Giannadaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Violeta Moniaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eleni Mauroudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stylianos Michelakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sophia E. Schiza
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Izolde Bouloukaki.

Additional information

Trial registry

ClinicalTrials.gov; No.:NCT02331940; URL: www.clinicaltrials.gov.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bouloukaki, I., Tzanakis, N., Mermigkis, C. et al. Tiotropium Respimat Soft Mist Inhaler versus HandiHaler to improve sleeping oxygen saturation and sleep quality in COPD. Sleep Breath 20, 605–612 (2016). https://doi.org/10.1007/s11325-015-1259-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11325-015-1259-y

Keywords

Search

Navigation