, Volume 195, Issue 5, pp 643–651 | Cite as

OSA and Prolonged Oxygen Desaturation During Sleep are Strong Predictors of Poor Outcome in IPF

  • Marcello BosiEmail author
  • Giulia Milioli
  • Francesco Fanfulla
  • Sara Tomassetti
  • Jay H. Ryu
  • Liborio Parrino
  • Silvia Riccardi
  • Andrea Melpignano
  • Anna Elisabetta Vaudano
  • Claudia Ravaglia
  • Paola Tantalocco
  • Andrea Rossi
  • Venerino Poletti



Sleep Breathing Disorders (SBD) are frequently found in idiopathic pulmonary fibrosis (IPF) and they are associated with worse quality of sleep and life and with higher mortality. The study aimed at evaluating the impact of SBD on prognosis (mortality or disease progression) in 35 patients with mild to moderate IPF.

Methods and Results

Obstructive sleep apnea (OSA) was diagnosed in 25/35 patients with IPF: 14/35 mild, 7/35 moderate, and 4/35 severe. According to the American Academy of Sleep Medicine (AASM) definition, sleep-related hypoxemia was found in 9/35 patients with IPF. According to the presence/absence of SBD, IPF patients were divided into 4 groups: NO-SBD group (Group A, 25.7%), OSA without sleep-related hypoxemia (Group B, 48.5%), OSA with sleep-related hypoxemia group (Group C, 22.8%), and only 1/35 had sleep-related hypoxemia without OSA(Group D, 2.8%). Statistical analysis was focused only on group A, B, and C. Patients with OSAS and sleep-related hypoxemia (Group C) had the worse prognosis, both in terms of mortality or clinical deterioration. SBD were the only independent risk factor (Cox Proportional Hazards Multiple Regression Analysis) for mortality (HR 7.6% IC 1.2–36.3; p = 0.029) and disease progression (HR 9.95% IC 1.8–644.9; p = 0.007).


SBD are associated with a worse prognosis, both in terms of mortality or clinical progression. The presence of SBD should be explored in all IPF patients.


Idiopathic pulmonary fibrosis Obstructive sleep apnea Sleep-related hypoxemia Mortality 



6 minutes walking test


6 minutes walking distance


Acute phase


Apnea hypopea index,


Body mass index


Diffusion lung capacity for carbon monoxide (% or predicted)


Forced expiratory volume in the first second


Forced vital capacity


Idiopathic pulmonary fibrosis


Oxygen desaturation index


Obstructive sleep apnea


Arterial carbon dioxide partial pressure


Arterial oxygen partial pressure


Death or the first episode of progression of disease


Respiratory disturbance index


Respiratory effort related arousal


Average SpO2 during sleep


Average SpO2 during wakefulness


Sleep Breathing Disorders


Sleep efficiency


% of total sleep time spent with SpO2 < 90%


Total sleep time


Ventilation/perfusion relationship


Wake time after sleep onset


Author Contributions

MB, GM, FF, and LP had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. MB, GM, FF, LP, ST, JHR, SR, AM, AEV, CR, PT, AR, VP contributed substantially to the study design, data analysis and interpretation, and the writing of the manuscript.

Compliance with Ethical Standards

Conflict of interest

This was not an industry supported study. Marcello Bosi, Giulia Milioli,Francesco Fanfulla, Sara Tomassetti, Jay H Ryu, Liborio Parrino, Silvia Riccardi, Andrea Melpignano, Anna Elisabetta Vaudano, Claudia Ravaglia, Paola Tantalocco, Andrea Rossi, and Venerino Poletti have indicated no financial conflict of interest.


  1. 1.
    Ley B, Ryerson CJ, Vittinghoff E, Ryu JH, Tomassetti S, Lee JS, Poletti V, Buccioli M, Elicker BM, Jones KD, King TE, Collard HR (2012) A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med 156:684–691. doi: 10.7326/0003-4819-156-10-201205150-00004 CrossRefPubMedGoogle Scholar
  2. 2.
    Drent M, du Bois RM, Poletti V (2003) Recent advances in the diagnosis and management of nonspecific interstitial pneumonia. Curr Opin Pulm Med 9:411–417CrossRefPubMedGoogle Scholar
  3. 3.
    Poletti V, Ravaglia C, Buccioli M, Tantalocco P, Piciucchi S, Dubini A, Carloni A, Chilosi M, Tomassetti S (2013) Idiopathic pulmonary fibrosis: diagnosis and prognostic evaluation. Respiration. 86:5–12. doi: 10.1159/000353580 CrossRefPubMedGoogle Scholar
  4. 4.
    De Vries J, Kessels BL, Drent M (2001) Quality of life of idiopathic pulmonary fibrosis patients. Eur Respir J 17:954–961CrossRefPubMedGoogle Scholar
  5. 5.
    Swigris JJ, Kuschner WG, Jacobs SS, Wilson SR, Gould MK (2005) Health-related quality of life in patients with idiopathic pulmonary fibrosis: a systematic review. Thorax 60:588–594. doi: 10.1136/thx.2004.035220 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Kreuter M, Wuyts W, Renzoni E, Koschel D, Maher TM, Kolb M, Weycker D, Spagnolo P, Kirchgaessler K-U, Herth FJF, Costabel U (2016) Antacid therapy and disease outcomes in idiopathic pulmonary fibrosis: a pooled analysis. Lancet Respir Med 4:381–389. doi: 10.1016/S2213-2600(16)00067-9 CrossRefPubMedGoogle Scholar
  7. 7.
    De Boer K, Lee JS (2016) Under-recognised co-morbidities in idiopathic pulmonary fibrosis: a review. Respirology 21:995–1004. doi: 10.1111/resp.12622 CrossRefPubMedGoogle Scholar
  8. 8.
    Papiris SA, Kagouridis K, Kolilekas L, Bouros D, Manali ED (2014) Idiopathic pulmonary fibrosis acute exacerbations: where are we now? Expert Rev Respir Med 8:271–273. doi: 10.1586/17476348.2014.896206 CrossRefPubMedGoogle Scholar
  9. 9.
    Papiris SA, Kagouridis K, Kolilekas L, Papaioannou AI, Roussou A, Triantafillidou C, Baou K, Malagari K, Argentos S, Kotanidou A, Karakatsani A, Manali ED (2015) Survival in Idiopathic pulmonary fibrosis acute exacerbations: the non-steroid approach. BMC Pulm Med. doi: 10.1186/s12890-015-0146-4 PubMedPubMedCentralGoogle Scholar
  10. 10.
    Jo HE, Randhawa S, Corte TJ, Moodley Y (2016) Idiopathic pulmonary fibrosis and the elderly: diagnosis and management considerations. Drugs Aging 33:321–334. doi: 10.1007/s40266-016-0366-1 CrossRefPubMedGoogle Scholar
  11. 11.
    Antoniou KM, Tomassetti S, Tsitoura E, Vancheri C (2015) Idiopathic pulmonary fibrosis and lung cancer: a clinical and pathogenesis update. Curr Opin Pulm Med 21:626–633. doi: 10.1097/MCP.0000000000000217 CrossRefPubMedGoogle Scholar
  12. 12.
    Mermigkis C, Stagaki E, Amfilochiou A, Polychronopoulos V, Korkonikitas P, Mermigkis D, Bregou M, Kouris N, Bouros D (2009) Sleep quality and associated daytime consequences in patients with idiopathic pulmonary fibrosis. Med Princ Pract 18:10–15. doi: 10.1159/000163039 CrossRefPubMedGoogle Scholar
  13. 13.
    Agarwal S, Richardson B, Krishnan V, Schneider H, Collop NA, Danoff SK (2009) Interstitial lung disease and sleep: what is known? Sleep Med 10:947–951. doi: 10.1016/j.sleep.2009.01.004 CrossRefPubMedGoogle Scholar
  14. 14.
    Perez-Padilla R, West P, Lertzman M, Kryger MH (1985) Breathing during sleep in patients with interstitial lung disease. Am Rev Respir Dis 132:224–229PubMedGoogle Scholar
  15. 15.
    Milioli G, Bosi M, Poletti V, Tomassetti S, Grassi A, Riccardi S, Terzano MG, Parrino L (2015) Sleep and respiratory sleep disorders in idiopathic pulmonary fibrosis. Sleep Med Rev 26:57–63. doi: 10.1016/j.smrv.2015.03.005 CrossRefPubMedGoogle Scholar
  16. 16.
    Schiza S, Mermigkis C, Margaritopoulos GA, Daniil Z, Harari S, Poletti V, Renzoni EA, Torre O, Visca D, Bouloukaki I, Sourvinos G, Antoniou KM (2015) Idiopathic pulmonary fibrosis and sleep disorders: no longer strangers in the night. Eur Respir Rev 24:327–339. doi: 10.1183/16000617.00009114 CrossRefPubMedGoogle Scholar
  17. 17.
    Ruhle K-H (2010) Commentary on how common is sleep-disordered breathing in patients with idiopathic pulmonary fibrosis? Mermigkis C. et al. Sleep Breath 14:289. doi: 10.1007/s11325-010-0341-8 CrossRefPubMedGoogle Scholar
  18. 18.
    Mermigkis C, Stagaki E, Tryfon S, Schiza S, Amfilochiou A, Polychronopoulos V, Panagou P, Galanis N, Kallianos A, Mermigkis D, Kopanakis A, Varouchakis G, Kapsimalis F, Bouros D (2010) How common is sleep-disordered breathing in patients with idiopathic pulmonary fibrosis? Sleep Breath 14:387–390. doi: 10.1007/s11325-010-0336-5 CrossRefPubMedGoogle Scholar
  19. 19.
    Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier J-F, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE, Kondoh Y, Myers J, Müller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schünemann HJ (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183:788–824. doi: 10.1164/rccm.2009-040GL CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Collard HR, Ryerson CJ, Corte TJ, Jenkins G, Kondoh Y, Lederer DJ, Lee JS, Maher TM, Wells AU, Antoniou KM, Behr J, Brown KK, Cottin V, Flaherty KR, Fukuoka J, Hansell DM, Johkoh T, Kaminski N, Kim DS, Kolb M, Lynch DA, Myers JL, Raghu G, Richeldi L, Taniguchi H, Martinez FJ (2016) Acute exacerbation of idiopathic pulmonary fibrosis. An International Working Group Report. Am J Respir Crit Care Med 194:265–275. doi: 10.1164/rccm.201604-0801CI CrossRefPubMedGoogle Scholar
  21. 21.
    The AASM Manual for the Scoring of Sleep and Associated Events (2014). Version 2.1, American academy of sleep medicineGoogle Scholar
  22. 22.
    American Academy of Sleep Medicine (2014). International Classification of Sleep Disorders, Third Edition., Am Acad Sleep MedGoogle Scholar
  23. 23.
    Kolilekas L, Manali E, Vlami KA, Lyberopoulos P, Triantafillidou C, Kagouridis K, Baou K, Gyftopoulos S, Vougas KN, Karakatsani A, Alchanatis M, Papiris S (2013) Sleep oxygen desaturation predicts survival in idiopathic pulmonary fibrosis. J Clin Sleep Med 9:593–601. doi: 10.5664/jcsm.2758 PubMedPubMedCentralGoogle Scholar
  24. 24.
    Becker HF, Piper AJ, Flynn WE, McNamara SG, Grunstein RR, Peter JH, Sullivan CE (1999) Breathing during sleep in patients with nocturnal desaturation. Am J Respir Crit Care Med 159:112–118. doi: 10.1164/ajrccm.159.1.9803037 CrossRefPubMedGoogle Scholar
  25. 25.
    Pitsiou G, Bagalas V, Boutou A, Stanopoulos I, Argyropoulou-Pataka P (2013) Should we routinely screen patients with idiopathic pulmonary fibrosis for nocturnal hypoxemia? Sleep Breath 17:447–448. doi: 10.1007/s11325-012-0716-0 CrossRefPubMedGoogle Scholar
  26. 26.
    Corte TJ, Wort SJ, Talbot S, Macdonald PM, Hansel DM, Polkey M, Renzoni E, Maher TM, Nicholson AG, Wells AU (2012) Elevated nocturnal desaturation index predicts mortality in interstitial lung disease. Sarcoidosis Vasc Diffuse Lung Dis 29:41–50PubMedGoogle Scholar
  27. 27.
    Mermigkis C, Bouloukaki I, Antoniou KM, Mermigkis D, Psathakis K, Giannarakis I, Varouchakis G, Siafakas N, Schiza SE (2013) CPAP therapy in patients with idiopathic pulmonary fibrosis and obstructive sleep apnea: does it offer a better quality of life and sleep? Sleep Breath 17:1137–1143. doi: 10.1007/s11325-013-0813-8 CrossRefPubMedGoogle Scholar
  28. 28.
    Mermigkis C, Bouloukaki I, Antoniou K, Papadogiannis G, Giannarakis I, Varouchakis G, Siafakas N, Schiza SE (2015) Obstructive sleep apnea should be treated in patients with idiopathic pulmonary fibrosis. Sleep Breath. 19:385–391. doi: 10.1007/s11325-014-1033-6 CrossRefPubMedGoogle Scholar
  29. 29.
    Mermigkis C, Bouloukaki I, Schiza SE (2013) Obstructive sleep apnea in patients with interstitial lung diseases: past and future. Sleep Breath 17:1127–1128. doi: 10.1007/s11325-013-0836-1 CrossRefPubMedGoogle Scholar
  30. 30.
    McNicholas WT, Coffey M, Fitzgerald MX (1986) Ventilation and gas exchange during sleep in patients with interstitial lung disease. Thorax 41:777–782CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Bye PT, Issa F, Berthon-Jones M, Sullivan CE (1984) Studies of oxygenation during sleep in patients with interstitial lung disease. Am Rev Respir Dis 129:27–32PubMedGoogle Scholar
  32. 32.
    Fanfulla F, Grassi M, Taurino AE, D’Artavilla Lupo N, Trentin R (2008) The relationship of daytime hypoxemia and nocturnal hypoxia in obstructive sleep apnea syndrome. Sleep 31:249–255CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Lacedonia D, Carpagnano GE, Aliani M, Sabato R, Foschino Barbaro MP, Spanevello A, Carone M, Fanfulla F (2013) Daytime PaO2 in OSAS, COPD and the combination of the two (overlap syndrome). Respir Med 107:310–316. doi: 10.1016/j.rmed.2012.10.012 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Marcello Bosi
    • 1
    Email author
  • Giulia Milioli
    • 2
  • Francesco Fanfulla
    • 3
  • Sara Tomassetti
    • 1
  • Jay H. Ryu
    • 4
  • Liborio Parrino
    • 2
  • Silvia Riccardi
    • 2
  • Andrea Melpignano
    • 2
  • Anna Elisabetta Vaudano
    • 2
  • Claudia Ravaglia
    • 1
  • Paola Tantalocco
    • 1
  • Andrea Rossi
    • 4
  • Venerino Poletti
    • 1
    • 2
    • 3
    • 4
    • 5
    • 6
  1. 1.Department of Diseases of the ThoraxGB Morgagni Hospital, Asl RomagnaForlìItaly
  2. 2.Sleep Disorders Center, Dept of NeurosciencesUniversity of ParmaParmaItaly
  3. 3.Sleep Medicine Unit and Sleep Research Laboratory S. Maugeri Foundation IRCCS – Scientific Insitute of PaviaPaviaItaly
  4. 4.Division of Pulmonary and Critical Care MedicineMayo ClinicRochesterUSA
  5. 5.Pulmonology Operative UnitVerona UniversityVeronaItaly
  6. 6.Department of Respiratory Diseases & AllergyAarhus University HospitalAarhusDenmark

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