Skip to main content
Download PDF

Hypo- and hypercapnia predict mortality in oxygen-dependent chronic obstructive pulmonary disease: a population-based prospective study

Respiratory Research volume 15, Article number: 30 (2014) Cite this article

Abstract

Background

The prognostic role of the arterial blood gas tension of carbon dioxide (PaCO2) in severe Chronic Obstructive Pulmonary Disease (COPD) remains unknown. The aim of this study was to estimate the association between PaCO2 and mortality in oxygen-dependent COPD.

Methods

National prospective study of patients starting long-term oxygen therapy (LTOT) for COPD in Sweden between October 1, 2005 and June 30, 2009, with all-cause mortality as endpoint. The association between PaCO2 while breathing air, PaCO2 (air), and mortality was estimated using Cox regression adjusted for age, sex, arterial blood gas tension of oxygen (PaO2), World Health Organization performance status, body mass index, comorbidity, and medications.

Results

Of 2,249 patients included, 1,129 (50%) died during a median 1.1 years (IQR 0.6-2.0 years) of observation. No patient was lost to follow-up. PaCO2 (air) independently predicted adjusted mortality (p < 0.001). The association with mortality was U-shaped, with the lowest mortality at approximately PaCO2 (air) 6.5 kPa and increased mortality at PaCO2 (air) below 5.0 kPa and above 7.0 kPa.

Conclusion

In oxygen-dependent COPD, PaCO2 (air) is an independent prognostic factor with a U-shaped association with mortality.

Introduction

Advanced chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality [1]. Although long-term oxygen therapy (LTOT) decreases mortality in patients with advanced COPD and chronic hypoxemia [2, 3], the prognosis is poor with a mortality rate of 51% at 2 years [4]. Predictors of mortality in oxygen-dependent COPD include sex, age, body mass index (BMI), comorbidities, forced expiratory volume in one second (FEV1), and arterial blood gas tension of oxygen (PaO2) [5–14].

The prognostic role of PaCO2 in oxygen-dependent COPD remains unknown. PaCO2 while breathing air, PaCO2 (air), has been associated with both increased mortality [5], decreased mortality [15], and no association with mortality [4, 16].

Defining the predictive role of PaCO2 (air) on mortality is important for several reasons. Despite the data being inconsistent, clinicians often regard hypercapnia (PaCO2 > 6.5 kPa) as an indicator of more severe respiratory disease, worse prognosis, and higher risk of complications from oxygen therapy including respiratory depression. High-flow oxygen given pre-hospital to patients with likely COPD exacerbation was recently associated with increased risk of acute hypercapnia and mortality [17]. Guidelines recommend titration of oxygen dose in hospital to avoid possible adverse effects when LTOT is initiated in a patient with hypercapnia [18]. Hypercapnia might indicate the presence of a concurrent hypoventilation syndrome in COPD, which is associated with shorter survival [19]. In addition, knowledge on predictors of mortality is needed as a prognostic model for patients with oxygen-dependent COPD is lacking.

The aim of this nationwide prospective study was therefore to estimate the association between PaCO2 (air) and mortality in oxygen-dependent COPD.

Materials and methods

We prospectively included patients from the National Register for Long Term Oxygen Therapy (Swedevox) with physician-diagnosed COPD who started LTOT between October 1, 2005 and June 30, 2009. Swedevox is a health quality register run by the health professionals and with financial support from the government. Swedevox has a population-based coverage of approximately 85% of patients starting LTOT in Sweden since 1987 [20]. Details of the register were described in a recently published study using the same database [21]. For patients who had started LTOT more than once (n = 62), only the most recent treatment episode was included in the analysis. Exclusion criterion was a diagnosis of lung cancer before starting LTOT (baseline).

Data on comorbidity and time spent in hospital during the four-year period before baseline were obtained from the National Patient Register for in- and outpatient care [22]. Diagnoses were coded according to the ninth (before 1997) [23] and tenth revisions of the International Classification of Disease (ICD) [24]. Possible comorbid hypoventilation was defined as hypoxia with a normal alveolar-arterial oxygen tension difference, (P[A-a]O2), of < 3 kPa, or a prior diagnosis (ICD-9; ICD-10) which may cause hypoventilation [25]: scoliosis (737.4; M41), spinal muscular atrophy (335.1; G12), muscular dystrophy (335.2; G71), myasthenia gravis (358; G70), post-polio syndrome (138; G14), sequelae of poliomyelitis (B91.9), sequelae of respiratory tuberculosis (137; B90.9), obstructive sleep apnea (327.2; G47.3), obesity hypoventilation syndrome (278.0; E66.2), or prolonged mechanical ventilation (DG008, AG063; 93.90, 96.70).

Data on all dispensed drug prescriptions in outpatient care after July 1, 2005 were obtained from the Swedish Prescribed Drug Register [26]. Patients were followed until withdrawal of LTOT, death, or December 31, 2009, whichever came first. The primary endpoint was all-cause mortality, obtained from the Swedish Causes of Death Register.

All patients participating in the study were informed according to directives from the authorities. The study was approved by all the relevant ethics committees in Sweden, the Swedish National Board of Health and Welfare, and the Swedish Data Inspection Board.

Statistical analysis

Baseline patient characteristics were summarized using mean with standard deviation (SD) and median with range or interquartile range (IQR) for continuous variables with normal and skewed distribution, respectively. Categorical variables were expressed as frequencies and percentages. The differences among the groups were tested with t-test for continuous variables and chi-square test for categorical variables.

Missing elements were imputed for PaO2 (air) (n = 289), PaCO2 (air) (n = 301), PaO2 (oxygen) (n = 210), PaCO2 (oxygen) (n = 213), FEV1 (n = 849), and body mass index (BMI) (n = 701), as previously described [21]. The model estimates were robust to the imputations. P[A-a]O2 was calculated using the alveolar gas equation: P[A-a]O2 = PiO2 - (PaCO2/R) - PaO2. Change in PaCO2 was defined as a difference between PaCO2 (oxygen) and PaCO2 (air) of 0.3 kPa or more.

Association between PaCO2 (air) and mortality was estimated using Cox multiple regression, adjusting for baseline age, sex, PaO2 (air), World Health Organization (WHO) performance status, BMI, number of cardiovascular diagnoses (cerebrovascular disease, heart failure, hypertension, ischemic heart disease, peripheral artery disease, pulmonary embolism, and other circulatory disease), treatment with oral glucocorticoids, benzodiazepines, and opioids. The model included a linear and a squared term for PaCO2 (air) to evaluate nonlinear associations. Higher-order terms did not improve the model with regard to diagnostics. Mortality estimates were expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Statistical significance was defined as a two-sided p-value of < 0.05.

Statistical analyses were conducted using the software packages Stata, version 12 (StataCorp LP; College Station, TX), and SAS, version 9.2 (SAS Institute, Inc., Cary, NC).

Results

A total of 2,249 patients were included. No patient was lost to follow-up. The cohort generated 3,118 person-years at risk during a median 1.1 years (IQR, 0.6–2.0 years) of follow-up. During this time, 1,129 (50%) patients died. The main causes of death were respiratory disease (68%), cardiovascular disease (20%), and cancer (6%). LTOT was withdrawn for other reasons than death in 138 (6%) patients, mainly because of improved oxygenation.

Patient characteristics at baseline are shown in Table 1. Hypercapnia (PaCO2 (air) > 6.5 kPa) was present in 39% of patients. After initiating LTOT, PaCO2 increased in 45% of patients, decreased in 19%, and remained unchanged (difference less than 0.3 kPa) in 36%. Of patients with hypercapnia, 37% increased in PaCO2 after starting LTOT, whereas 30% decreased to a PaCO2 below 6.5 kPa.

Table 1 Patient characteristics at baseline
Full size table

Hypercapnic patients were prescribed a slightly lower median oxygen dose than normocapnic patients, 1 (IQR, 1–1.5) vs. 1.5 (IQR, 1–2) l/min (p < 0.001). In total, 29% of patients started LTOT in hospital. A slightly greater proportion of patients with hypercapnia (31%) than normocapnic patients (27%) started LTOT in hospital (p = 0.039).

Effects on mortality

PaCO2 (air) independently predicted adjusted mortality (p < 0.001), as shown in Table 2. The association with mortality exhibited a U-shaped pattern, with lowest mortality at approximately PaCO2 (air) 6.5 kPa and increased mortality below 5.0 kPa and above 7.0 kPa (Figure 1). Compared to a PaCO2 (air) of 6.5 kPa, a PaCO2 (air) of ≤ 4.5 kPa increased mortality by 17% or more, and a PaCO2 (air) of ≥ 8.0 kPa increased mortality by at least 15%. Excluding patients with possible hypoventilation (n = 122) did not alter the estimates. Sensitivity analysis only including patients with FEV1/FVC < 0.7 did not alter the results.

Table 2 Cox regression of all-cause mortality in 2,249 patients on long-term oxygen therapy for COPD
Full size table
Figure 1
figure 1

PaCO 2 and adjusted mortality in oxygen-dependent COPD. Hazard ratio of death for different levels of PaCO2 (air) compared to at PaCO2 (air) = 6.5 kPa, adjusted for age, sex, PaO2 (air), WHO performance status, BMI, number of cardiovascular diagnoses, and treatment with oral glucocorticoids, benzodiazepines and opioids. Abbreviations: PaCO2 (air), Arterial blood gas tension of carbon dioxide on air; PaO2 (air), Arterial blood gas tension of oxygen on air; WHO, World Health Organization; BMI, Body Mass Index.

Full size image

P[A-a]O2 did not predict adjusted mortality (p = 0.342), when included instead of PaO2 and PaCO2. Changes in PaCO2 when starting LTOT did not affect adjusted mortality; neither a rise in PaCO2 (p = 0.227) or a fall in PaCO2 (p = 0.355).

Discussion

The novel finding in the present study is that PaCO2 (air) has an U-shaped association with mortality in oxygen-dependent COPD. PaCO2 (air) values lower than 5.0 kPa and higher than 7.0 kPa were associated with increased mortality.

Previous findings on the association between PaCO2 and mortality have been conflicting. Our results are consistent with studies reporting increased mortality associated with either hypocapnia [5, 27] or hypercapnia [3, 28, 29]. In a large study of COPD patients on LTOT, Chailleux et al. found PaCO2 to be an independent negative predictor at 3 years follow-up [5]. However, Aida and colleagues found no association between PaCO2 (air) and mortality [16]. As none of the previous studies, to our knowledge, evaluated the shape of the association, the discrepancy between the findings of previous studies may partly owe to that they did not account for a nonlinear association.

Strengths of the present study include its national prospective design and that it included a large cohort of both men and women with oxygen-dependent COPD. No patient was lost to follow-up. The analysis was adjusted for relevant confounders, including comorbidity and exposure to benzodiazepines and opioids. A limitation of the study is that we lacked data on pH and base excess and could not evaluate the chronicity of the respiratory failure or the level of metabolic compensation. Nevertheless, the study presents data on the prognostic role of PaCO2 in patients starting LTOT for COPD that are likely to be applicable to current clinical practice.

An interesting additional finding was the large variability in the change in PaCO2 when starting LTOT. There is concern among clinicians that the level of PaCO2 will increase after starting LTOT, especially in hypercapnic patients. In the present study, 30% of patients with hypercapnia actually decreased their PaCO2 to below 6.5 kPa after initiation of LTOT and PaCO2 remained unchanged in 36% of patients. This may be explained by regression to the mean and by improving blood gases over time in patients starting LTOT in relation to an exacerbation. The change in PaCO2 between breathing room air and breathing oxygen (LTOT) did not predict mortality. This suggests that some increase in PaCO2 from baseline when starting LTOT is well-tolerated and not associated with worse prognosis.

Which mechanisms underpin the association between blood gas disturbances and mortality? The lack of a clear association between P[A-a]O2 and mortality implies that gas exchange inefficiency is not the main driver behind the increased mortality associated with hypoxemia and hypo- and hypercapnia. Our study suggests that the level of alveolar ventilation predicts mortality independently of the level of hypoxemia. Factors contributing to the increasing mortality could include more severe underlying COPD, respiratory maladaptation, and the presence of comorbidities. In hypocapnia, increased minute ventilation may cause respiratory muscle fatigue, hastened ventilatory failure and death. This might reflect a relative inability among these patients to adapt their breathing pattern to avoid respiratory muscle fatigue. Comorbidities such as congestive heart failure or pulmonary embolism may also contribute to the increased ventilation and worse prognosis. Modest hypercapnia may reflect an adaptive alveolar hypoventilation, which occurs (unconsciously) to minimize dyspnea and respiratory muscle fatigue. While modest hypercapnia were not associated with earlier death, PaCO2 (air) exceeding 7.0 kPa seemed to be maladaptive and associated with increased mortality rates. Mechanical defects of the chest wall, such as kyphoscoliosis, and hyperinflation may predispose to alveolar hypoventilation by imposing additional work on the inspiratory muscles [30]. Concurrent hypoventilation syndrome may contribute to hypercapnia in some COPD patients, requiring treatment with home mechanical ventilation in addition to oxygen therapy [31]. However, it is still unclear whether long-term non-invasive home ventilation improves prognosis in patients with stable hypercapnic COPD [32].

For clinicians, this study suggests that patients with PaCO2 (air) below 5 kPa or above 7 kPa are at increased risk of death and should be optimally treated and carefully followed. Furthermore, patients with hypo- or hypercapnia should be evaluated for comorbid diseases, including heart failure and hypoventilation syndromes. The U-shaped association of PaCO2 (air) with overall mortality should be validated by further studies and incorporated in future prognostic models of patients with advanced COPD.

Conclusion

In conclusion, the level of alveolar ventilation, as reflected by both hypo- and hypercapnia, predicts mortality in oxygen-dependent COPD.

Abbreviations

BMI:

Body mass index

CI:

Confidence interval

COPD:

Chronic obstructive pulmonary disease

HR:

Hazard ratio

ICD:

International classification of disease

IQR:

Interquartile range

FEV1:

Forced expiratory volume in one second

LTOT:

Long-term oxygen therapy

P[A-a]O2:

Alveolar-arterial oxygen tension difference

PIO2:

Inspired partial pressure of oxygen

R:

Respiratory quotient, normally 0.8

PaO2:

Arterial blood gas tension of oxygen

PaCO2:

Arterial blood gas tension of carbon dioxide

PaO2 (air):

Arterial blood gas tension of oxygen on air

PaO2 (oxygen):

Arterial blood gas tension of oxygen on oxygen

PaCO2 (air):

Arterial blood gas tension of carbon dioxide on air

PaCO2 (oxygen):

Arterial blood gas tension of carbon dioxide on oxygen

Ref:

Reference category

SD:

Standard deviation

WHO:

World health organization.

References

  1. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011. 2011, Available from http://www.goldcopd.org/

  2. Nocturnal Oxygen Therapy Trial Group: Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med. 1980, 93: 391-398.

    Article  Google Scholar 

  3. Report of the Medical Research Council Working Party: Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet. 1981, 1: 681-686.

    Google Scholar 

  4. Crockett AJ, Cranston JM, Moss JR, Alpers JH: Survival on long-term oxygen therapy in chronic airflow limitation: from evidence to outcomes in the routine clinical setting. Intern Med J. 2001, 31: 448-454. 10.1046/j.1445-5994.2001.00103.x.

    Article  PubMed  CAS  Google Scholar 

  5. Chailleux E, Fauroux B, Binet F, Dautzenberg B, Polu JM: Predictors of survival in patients receiving domiciliary oxygen therapy or mechanical ventilation. A 10-year analysis of ANTADIR Observatory. Chest. 1996, 109: 741-749. 10.1378/chest.109.3.741.

    Article  PubMed  CAS  Google Scholar 

  6. Dolan S, Varkey B: Prognostic factors in chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2005, 11: 149-152. 10.1097/01.mcp.0000153548.36054.8f.

    Article  PubMed  Google Scholar 

  7. Costello R, Deegan P, Fitzpatrick M, McNicholas WT: Reversible hypercapnia in chronic obstructive pulmonary disease: a distinct pattern of respiratory failure with a favorable prognosis. Am J Med. 1997, 102: 239-244. 10.1016/S0002-9343(97)00017-X.

    Article  PubMed  CAS  Google Scholar 

  8. Celli BR: Predictors of mortality in COPD. Respir Med. 2010, 104: 773-779. 10.1016/j.rmed.2009.12.017.

    Article  PubMed  Google Scholar 

  9. Budweiser S, Jorres RA, Riedl T, Heinemann F, Hitzl AP, Windisch W, Pfeifer M: Predictors of survival in COPD patients with chronic hypercapnic respiratory failure receiving noninvasive home ventilation. Chest. 2007, 131: 1650-1658. 10.1378/chest.06-2124.

    Article  PubMed  Google Scholar 

  10. Anthonisen NR: Home oxygen therapy in chronic obstructive pulmonary disease. Clin Chest Med. 1986, 7: 673-678.

    PubMed  CAS  Google Scholar 

  11. Miyamoto K, Aida A, Nishimura M, Aiba M, Kira S, Kawakami Y: Gender effect on prognosis of patients receiving long-term home oxygen therapy. The respiratory failure research group in Japan. Am J Respir Crit Care Med. 1995, 152: 972-976. 10.1164/ajrccm.152.3.7663812.

    Article  PubMed  CAS  Google Scholar 

  12. Nizet TA, van den Elshout FJ, Heijdra YF, van de Ven MJ, Mulder PG, Folgering HT: Survival of chronic hypercapnic COPD patients is predicted by smoking habits, comorbidity, and hypoxemia. Chest. 2005, 127: 1904-1910. 10.1378/chest.127.6.1904.

    Article  PubMed  Google Scholar 

  13. Strom K, Boman G: Long-term oxygen therapy in parenchymal lung diseases: an analysis of survival. The Swedish Society of Chest Medicine. Eur Respir J. 1993, 6: 1264-1270.

    PubMed  CAS  Google Scholar 

  14. Oga T, Nishimura K, Tsukino M, Sato S, Hajiro T: Analysis of the factors related to mortality in chronic obstructive pulmonary disease: role of exercise capacity and health status. Am J Respir Crit Care Med. 2003, 167: 544-549. 10.1164/rccm.200206-583OC.

    Article  PubMed  Google Scholar 

  15. Dubois P, Jamart J, Machiels J, Smeets F, Lulling J: Prognosis of severely hypoxemic patients receiving long-term oxygen therapy. Chest. 1994, 105: 469-474. 10.1378/chest.105.2.469.

    Article  PubMed  CAS  Google Scholar 

  16. Aida A, Miyamoto K, Nishimura M, Aiba M, Kira S, Kawakami Y: Prognostic value of hypercapnia in patients with chronic respiratory failure during long-term oxygen therapy. Am J Respir Crit Care Med. 1998, 158: 188-193. 10.1164/ajrccm.158.1.9703092.

    Article  PubMed  CAS  Google Scholar 

  17. Austin MA, Wills KE, Blizzard L, Walters EH, Wood-Baker R: Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010, 341: c5462-10.1136/bmj.c5462.

    Article  PubMed  PubMed Central  Google Scholar 

  18. The Swedish national register for patients on Long Term Oxygen Therapy and Home Mechanical Ventilation (Swedevox). Available from http://www.ucr.uu.se/swedevox/index.php. [http://www.ucr.uu.se/swedevox/]

  19. Marin JM, Soriano JB, Carrizo SJ, Boldova A, Celli BR: Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med. 2010, 182: 325-331. 10.1164/rccm.200912-1869OC.

    Article  PubMed  Google Scholar 

  20. Strom K, Boe J: A national register for long-term oxygen therapy in chronic hypoxia: preliminary results. Eur Respir J. 1988, 1: 952-958.

    PubMed  CAS  Google Scholar 

  21. Ekstrom MP, Bornefalk Hermansson A, Strom KE: Effects of cardiovascular drugs on mortality in severe chronic obstructive pulmonary disease: a time-dependent analysis. Am J Respir Crit Care Med. 2013, 187 (7): 715-720. 10.1164/rccm.201208-1565OC.

    Article  PubMed  Google Scholar 

  22. Swedish National Board of Health and Welfare: Quality and Contents of the Swedish Hospital Discharge Register. 2008, Stockholm: Swedish National Board of Health and Welfare. The Center for Epidemiology

    Google Scholar 

  23. World Health Organization: Manual of the International Classification of Diseases, Injuries and Causes of Death. 9th revision., vol. 1. 1978, Geneva, Switzerland: World Health Organization

    Google Scholar 

  24. World Health Organization: Manual of the International Statistical Classification of Diseases and Health Related Problems. 10th revision., vol. 1. 1992, Geneva, Switzerland: World Health Organization

    Google Scholar 

  25. Duffin J, Phillipson E: Hypo and hyperventilation syndromes. Murray and Nadel’s Textbook of Respiratory Medicine. Edited by: Mason R, Broaddus CV, Martin T, King TJr, Scharaufnagel D, Murray J. 2010, JA N. Philadelphia: Saunders, 1859-1880.

    Chapter  Google Scholar 

  26. Wettermark B, Hammar N, Fored CM, Leimanis A, Otterblad Olausson P, Bergman U, Persson I, Sundstrom A, Westerholm B, Rosen M: The new Swedish Prescribed Drug Register--opportunities for pharmacoepidemiological research and experience from the first six months. Pharmacoepidemiol Drug Saf. 2007, 16: 726-735. 10.1002/pds.1294.

    Article  PubMed  Google Scholar 

  27. Lima DF, Dela Coleta K, Tanni SE, Silveira LV, Godoy I, Godoy I: Potentially modifiable predictors of mortality in patients treated with long-term oxygen therapy. Respir Med. 2011, 105: 470-476. 10.1016/j.rmed.2010.08.012.

    Article  PubMed  Google Scholar 

  28. Cooper CB, Waterhouse J, Howard P: Twelve year clinical study of patients with hypoxic cor pulmonale given long term domiciliary oxygen therapy. Thorax. 1987, 42: 105-110. 10.1136/thx.42.2.105.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Foucher P, Baudouin N, Merati M, Pitard A, Bonniaud P, Reybet-Degat O, Jeannin L: Relative survival analysis of 252 patients with COPD receiving long-term oxygen therapy. Chest. 1998, 113: 1580-1587. 10.1378/chest.113.6.1580.

    Article  PubMed  CAS  Google Scholar 

  30. Roussos C, Koutsoukou A: Respiratory failure. Eur Respir J Suppl. 2003, 47: 3s-14s.

    Article  PubMed  CAS  Google Scholar 

  31. Gustafson T, Franklin KA, Midgren B, Pehrsson K, Ranstam J, Strom K: Survival of patients with kyphoscoliosis receiving mechanical ventilation or oxygen at home. Chest. 2006, 130: 1828-1833. 10.1378/chest.130.6.1828.

    Article  PubMed  Google Scholar 

  32. Struik FM, Lacasse Y, Goldstein R, Kerstjens HM, Wijkstra PJ: Nocturnal non-invasive positive pressure ventilation for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2013, 6: CD002878-

    PubMed  Google Scholar 

Download references

Acknowledgements

The work was carried out at the Department of Respiratory Medicine, Blekinge Hospital Karlskrona, University of Lund, Sweden. We thank Kerstin Ström for being a constant inspiration and all the physicians and nurses who collected the data and cared for the patients.

Funding

This study was funded by the Research Council of Blekinge, the Swedish Heart-Lung Foundation, and the Swedish National Board of Health and Welfare.

Author information

Authors and Affiliations

  1. Department of Medicine, Blekinge Hospital, 37185, Karlskrona, Sweden

    Zainab Ahmadi & Magnus P Ekström

  2. Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden

    Anna Bornefalk-Hermansson

  3. Department of Surgical and Perioperative Sciences, Surgery, University Hospital of Umeå, Umeå, Sweden

    Karl A Franklin

  4. Department of Clinical Sciences, Lund, Division of Respiratory Medicine & Allergology, Lund University Hospital, Lund, Sweden

    Bengt Midgren & Magnus P Ekström

Authors
  1. Zainab Ahmadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna Bornefalk-Hermansson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karl A Franklin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bengt Midgren
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Magnus P Ekström
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zainab Ahmadi.

Additional information

Competing interests

The authors declare that they have no competing interest.

Authors’ contributions

ME had full access to all the data in the study and takes full responsibility for the integrity of the data and the accuracy of the data analysis. Conception and design: ABH, ME, ZA; acquisition of data: BM, ME; analysis and interpretation of data: ABH, BM, KF, ME, ZA; drafting the article: ABH, ME, ZA; revision for important intellectual content and approval of the version to be published: ABH, BM, KF, ME, ZA. All authors read and approved the final manuscript.

Authors’ original submitted files for images

Below are the links to the authors’ original submitted files for images.

Authors’ original file for figure 1

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Cite this article

Ahmadi, Z., Bornefalk-Hermansson, A., Franklin, K.A. et al. Hypo- and hypercapnia predict mortality in oxygen-dependent chronic obstructive pulmonary disease: a population-based prospective study. Respir Res 15, 30 (2014). https://doi.org/10.1186/1465-9921-15-30

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/1465-9921-15-30

Keywords