Sleep pattern in patients with Chronic Obstructive Pulmonary Disease and correlation among gasometric, spirometric, and polysomnographic variables

Padrão do sono em pacientes portadores de doença pulmonar obstrutiva crônica e correlação entre variáveis gasométricas, espirométricas e polissonográficas

ORIGINAL ARTICLE

Sleep pattern in patients with Chronic Obstructive Pulmonary Disease and correlation among gasometric, spirometric, and polysomnographic variables^*

Padrão do sono em pacientes portadores de doença pulmonar obstrutiva crônica e correlação entre variáveis gasométricas, espirométricas e polissonográficas

Carlos Eduardo Ventura Gaio dos Santos^I (TE SBPT); Carlos Alberto de Assis Viegas^II (TE SBPT)

^IMaster from Health Sciences School of the Universidade de Brasília. Pneumologist of the University Hospital of Brasília. ICU Doctor of the Hospital de Base do Distrito Federal. Specialist Degree from SBPT

^IIDoctor in Medicine from Universidade de Barcelona. Associate Professor of the Universidade de Brasília. Specialist Degree from SBPT

^{Correspondence}

ABSTRACT

OBJECTIVE: There are few studies on chronic obstructive pulmonary disease (COPD) establishing differences between the functional parameters of the disease and sleep variables. The aim of the study was to describe the sleep pattern of these patients and to correlate spirometric, gasometric and polysomnographic variables.

METHODS: Transversal study using COPD patients submitted to spirometry, arterial gasometry, and polysomnography.

RESULTS: 21 male patients were studied with average age = 67 ± 9; 7 ± 4 average points in the Epworth sleepiness scale, average Tiffenau's index (FEV₁/FVC) = 54 ± 13.0%, average PaO₂ = 68 ± 11 mmHg, average PaCO₂ = 37 ± 6 mmHg. Sleep efficiency decreased (65 ± 16%) with the reduction of slow wave sleep (8 ± 9%) and rapid eye movement (REM) sleep (15 ± 8%). Average T90 was 43 ± 41%. Average apnea-hypopnea index (AHI) = 3 ± 5/h, where two patients (9.5%) presented obstructive sleep apnea. A significant correlation was observed between PaO₂ and T90 (p < 0.01), PaCO₂ and T90 (p < 0.05), and AHI and the cardiac rate during REM (p < 0.01). A higher number of arousals and stage change was observed. There was no linear correlation between spirometric and polysomnographic variables.

CONCLUSION: Poor sleep quality of these patients was characterized by low sleep efficiency, high number of awakenings and shift of stages. There were no correlations between the spirometric and polysomnographic variables.

Key words: Pulmonary disease, chronic obstructive. Sleep. Polysomnography. Arterial blood gases. Spirometry.

RESUMO

OBJETIVOS: Pouco se investigou o sono de pacientes portadores de doença pulmonar obstrutiva crônica (DPOC) estabelecendo comparações entre parâmetros funcionais e polissonográficos. Este estudo objetiva descrever o sono desses indivíduos e correlacionar variáveis espirométricas, gasométricas e polissonográficas.

MÉTODOS: Estudo transversal em portadores de DPOC, avaliando espirometria, gasometria arterial e polissonografia.

Resultados: Avaliados 21 pacientes masculinos com idade = 67 ± 9 anos, na escala de sonolência de Epworth (ESE) = 7 ± 4 pontos, índice de Tiffenau (VEF₁/CVF) = 54 ± 13,0%, PaO₂ = 68 ± 11mmHg, PaCO₂ = 37 ± 6mmHg. A eficiência do sono foi diminuída (65 ± 16%) com redução do sono de ondas lentas (8 ± 9%) e da fase do sono de movimento rápido dos olhos (REM) (15 ± 8%). T₉₀ médio = 43 ± 41% . Índice de apnéia-hipopnéia médio = 2,9 ± 5,2/h, sendo que dois pacientes (9,5%) apresentaram apnéia obstrutiva do sono. Observou-se correlação significativa entre PaO₂ e T₉₀ (p < 0,01), PaCO₂ e T₉₀ (p < 0,05) e IAH e freqüência cardíaca durante o REM (p < 0,01). Foi também observado elevado número de despertares e de mudanças de estágio. Não houve correlações lineares entre variáveis espirométricas e polissonográficas. Conclusões: Observou-se má qualidade de sono nesses pacientes, caracterizada por baixa eficiência do sono e elevado número de despertares e mudanças de estágios. Não foram observadas correlações entre variáveis espirométricas e polissonográficas.

Descritores: Doença pulmonar obstrutiva crônica. Sono. Polissonografia. Gasometria. Espirometria.

Abbreviations used in the present paper

%@S – Percentage of TST in stages 3 and 4

%S1 – Percentage of TST in stage 1

%S2 – Percentage of TST in stage 2

%SREM – Percentage of TST in REM sleep

%FVC – Percentage of forced vital capacity in regard to predicted value

%FEV₁ – Percentage of forced expiratory volume in the first sec

AHI – Apnea-hypopnea index

Arou – Microarousals

BM – Body movements

CA – Number of central apneas

COPD – Chronic obstructive pulmonary disease

ESS –Epworth Sleepiness Scale

FEV₁ – Forced expiratory volume in the first sec

FEV₁/FVC –Tiffenau's Index

FVC – Forced vital capacity

HO – Hypopnea

Lat – Sleep latency

LatREM – Latency to REM sleep

LM – Leg movements

MA – Number of mixed apneas

NREM – Non rapid eye movement

NREMHR – Heart rate during NREM sleep

OA – Number of obstructive apneas

OSAS – Obstructive sleep apnea syndrome

PaCO₂ – Partial CO₂ arterial pressure

PaO₂ – Partial O₂ arterial pressure

REM – Rapid eye movement

REMHR – Heart rate during REM sleep

RFC – Residual Functional Capacity

SC – Stage change

SEf – Sleep Efficiency

SpO₂NREM – Oxygen saturation during non REM sleep

SpO₂REM – Oxygen saturation during REM sleep

T90 – Percentage of sleep with hemoglobin saturation under 90%

TRT – Total recording time

Tsnor – Time of snoring

TSP – Total sleep period

TST – Total sleep time

INTRODUCTION

Several studies demonstrate PaO₂ reduction during sleep in COPD patients^(1,2), mainly during REM sleep^(3,4), being this decrease more pronounced during the tonic phase of this sleep stage⁽⁵⁾. It is natural to believe that hypoxemia is responsible for sleep fragmentation in COPD, and this hypothesis is supported by experimental studies⁽⁶⁾ and in diffuse parenchyma pulmonary disease patients^(7,8). Another hypothesis to explain sleep fragmentation is the hypercapnia, demonstrated in some studies^(9,10); subjects wake up with PaCO₂ close to 55 mmHg during NREM sleep and 60 mmHg during REM sleep. Paradoxically, predominantly emphysema patients, usually non-hypercapnic and non-hypoxemic, are the ones who present more sleep fragmentation, suggesting that yet another factor, such as increased ventilatory effort, is responsible for awakening⁽¹¹⁾.In addition, more hypoxemic individuals present a better sleep pattern, although they can evolve to cardiac arrhythmia⁽¹²⁾, right ventricle hypertrophy ⁽¹³⁾, polycitemia^(13,14) and pulmonary hypertension ⁽¹⁵⁾. The correlations between ventilatory functional tests of COPD patients and polysomnographic variables are still little studied. This study has the objective of examining possible correlations among spirometric, gasometric and polysomnographic variables in COPD patients.

METHODS

This is an analytical, transversal type of study, in which patients were included according to the following criteria: history of smoking, productive chronic cough and/or dyspnea, FEV₁/FVC index lower than 70% and irreversibility of bronchodilator spray-induced obstruction. Patients with other clinically or radiologically detectable lung illnesses or who presented any disease that had evolved to organ or system failure were excluded. This study was considered as "minimum risk" in human research⁽¹⁶⁾, and was approved by the Ethics Committee of the University Hospital of Brasília.

After accomplishment of the complete clinical history and physical examination, patients were submitted to arterial gasometry and spyrometry, always in the morning and by the same technician using Ciba Corning 278 Gas System^® (Ciba Corning, Diagnostics Corp, Medfield – USA) and Vmax^® – 22 series spirometer (SensorMedics Yorba Linda, Califórnia – USA), respectively.

The whole night polysomnographic recording was performed in the first night the patients slept in the laboratory by two trained and capable technicians, following the specifications and criteria established by Carskadon and Rechtschaffen⁽¹⁷⁾, using Alice 3^®(Infant and Adult Computorized Polysomnographic System, Geórgia, USA).

The following variables were presented by descriptive statistics: body mass index (BMI), Epworth Sleepiness Scale (ESS), FEV₁/FVC%, PaO₂, PaCO₂, total recording time (TRT), total sleep time (TST), sleep latency (Lat), latency to REM sleep (LatREM), snoring time (snorT), body movements (BM), leg movements (LM), changes of stage (CS), percentage of delta sleep (%DS), percentage of REM sleep (%REM), percentage of total sleep time in which hemoglobin saturation was below 90% (T₉₀), average heart rate during REM (HRREM) and non-REM (HRNREM) sleep and apnea and hypopnea index (AHI). Linear correlation analysis (Pearson Correlation) was performed among the above mentioned variables. Correlations were considered statistically significant when p < 0.05.

RESULTS

Twenty-one male patients with average age = 67.1 ± 8.6 years, BMI = 23.4 ± 3.9 kg/m² and smoking index = 74.1 ± 71.7 packs/years, were examined. Their average ESS score = 7.3 ± 4.4.

Mean values of spirometric and gasometric variables were: FVC = 2.85 ± 0.86 L, varying from 1.58 to 4.45 L; % FVC = 84.6 ± 24.0%; FEV₁ = 1.61± 0.75 L, varying from 0.65 to 2.71 L; % FEV₁ = 59.7 ± 27.0%; FVE₁/FVC = 54.1 ± 13.0%, with the lowest being 27% and the highest 69%; PaO₂ = 67.6 ± 10.9 mmHg, varying from 46.8 to 89.2 mmHg; PaCo₂ = 37.2 ± 5.5 mmHg, varying from 25.4 to 50.8 mmHg; SaO₂ = 92.5 ± 3.8%.

Mean polysomnographic values are presented in Table 1. Regarding the mean distribution of sleep stages, we observed a high percentage of stage 2 (%S2) = 51.4 ± 8.0% and low percentage of delta sleep (%DS) = 8.3 ± 7.7% and of REM sleep (%REMS) = 15.0 ± 8.3% (Table 2).

The mean number of obstructive apneas (AO) was 5.1 ± 12.1 and the mean apnea-hypopnea index (AHI) was 2.9 ± 5.2. Two patients presented AHI higher than 5, representing 9.5% of the sample under study. Hemoglobin saturation during NREM sleep (SpO₂ NREM) varied from 79% to 93%. During REM sleep, mean hemoglobin saturation (SpO₂REM) varied from 72% to 93%. The sample also exhibited a high mean percentage of TST in which hemoglobin saturation lower than 90% (T₉₀) was 43.4 41.2%. The other data are in Table 3.

Regarding the analysis of linear correlation, body mass index (BMI) and the results of the Epworth Sleepiness Scale were not correlated to any demographic, respiratory or polysomnographic variables. Regarding the FEV₁/FVC index, we observed an inverse significant correlation with PaCO₂ (r = -0.45; p < 0.05). In regard to the PaO₂, there was an inverse correlation with T₉₀ (r = -0.76; p < 0.01) (Figure 1). PaCO₂ correlated with AHI (r = -0.39; p < 0.05) (Figure 2) and with T₉₀ (r = 0.47; p < 0.05) (Figure 3). LatREM correlated directly and significantly with SC (r = 0.50; p < 0.05). %DS correlated with BM (r = -0.40; p < 0.05), with %S1 (r = -0.71; p < 0.05) and with AHI (r = -0.41; p < 0.05). AHI was directly and significantly correlated with REMHR (r = 0.77; p < 0.01) (Figure 4).

DISCUSSION

Our patients presented an average age in accordance to the consensus and epidemiological studies in COPD ^(18,19). All 21 individuals exhibited smoking as the likely cause of COPD and high pack/year index, characterizing the group as heavy smokers.

With respect to daytime hypersomnolence, the mean score in the Epworth sleepiness index was characterized as non-hypersomnolent; the correlation analysis did not confirm the associations between this index and the other variables studied.

Regarding the spirometric and gasometric values, we observed and important level of upper airways obstruction and discrete hypoxemia without hypercapnia.

Regarding polysomnographic data, our patients' exams were recorded in an ideal time of almost eight hours. However, we realized that the TST was lower than desired, of approximately 4.5 hours, values that are in accordance to the literature ^(20,21), for healthy individuals in this age range. Our group presented low SEf, considering that this variable in healthy subjects is approximately 80% ⁽²²⁾. We believe that the lower mean was due to the chronic respiratory failure. Regarding the sleep latency, the mean value was slightly above the expected ⁽²⁰⁾. Our sample showed mean body and leg movements similar to the literature ⁽²⁰⁾ for healthy individuals in the same age range. Therefore, some of our data are concordant with sleep descriptions in healthy subjects in the same age ⁽²³⁾. Nonetheless, we consider that the number of arousals and the number of SC is elevated when compared with subjects in the same age. However, there was no correlation between any of the variables and the daytime somnolence scale in this group.

Considering the distribution of sleep stages, some subjects preserved normal pattern, whereas others presented a reduction of slow wave sleep and of REM sleep. In contrast, there was a proportional increase of sleep stages 1 and 2. Since there is a large variation between normal percentage values and the standard deviation of the sample was large, we may consider that the mean values are within the limits of normality for subjects in this age. However, it must e emphasized that nine patients (43%) did not present sleep stages 3 and 4, and two of them did not present REM sleep, demonstrating the high prevalence of deprivation of these stages in this population.

Regarding the respiratory variables, we found that mean AHI was 2.9 and two patients exhibited an index higher than 5, characterizing OSAHS ⁽²⁴⁾. Thus, we obtained a 9.5% of the sample with the so-called overlap syndrome or mixed syndrome, an association between COPD and OSAHS. In 1980, Guilleminault and colleagues observed that 85% of 26 COPD patients presented elevated AHI, suggesting that COPD and OSAHS association is common ⁽²⁵⁾. Different results were published by other authors ^(26,27).In 1992, Tavares found a prevalence of 11.7% of COPD and OSAHS association in 17 patients and Chaouat and colleagues, in 1995, published a series of 265 COPD patients, where 11% presented mixed syndrome ⁽²⁹⁾. Therefore, our prevalence of 9.5% is close to more recent data.

Mean hemoglobin saturation of the group was 92.5 ± 3.8%. As known, there is a reduction of ventilation during anybody's sleep ⁽³⁰⁾. Due to such reduction and to factors inherent of COPD patients, such as the alteration of ventilation/perfusion ⁽²⁶⁾ and the reduction of FRC ^(31,32), the hemoglobin saturation averages during REM and NREM sleep were lower than 90%. Most of our patients presented high TST, with hemoglobin saturation under 90% (T₉₀), making them more prone to complications due to bad oxygenation ^(24,33).

Investigation of possible correlations among spirometric, gasometric and polysomnographic variables showed that most of the statistically significant correlations remained within sleep variables, such as percentage of slow wave sleep and REM sleep with body movements and stage changes. That means that the lower the percentage of these stages the highest will be stage change and body movements, characterizing the sleep shallowness in these individuals, which seems natural. Still among polysomnographic variables, an inverse correlation between AHI and %REMS, in accordance with the literature, as in the recent review of the American Sleep Association ⁽³⁴⁾. But it is between AHI and heart rate during REM sleep that an important correlation happens, demonstrating the well-known post-apnea tachicardia ^(24,34). Another established correlation is the level of obstruction, measured by the FEV₁/FVC index and the PaCO₂, demonstrating that, the most severe the obstruction the highest the PaCO₂ level. These data contradict some authors who concluded that there is no correlation between spirometric and gasometric variables in most of COPD patients ⁽³⁵⁾. No correlations between spirometric and polysomnographic variables occurred. However, among gasometric variables there were three important correlations: PaO₂ and T₉₀, which is natural, since the lowest the PaO₂ the longest the period of saturation under 90% during TST; PaCO₂ and T₉₀, revealing that patients more prone to hypercapnia exhibited longer time of hypoxia during sleep; and PaCO₂ and AHI, which, although being significant, may not have a significant biological meaning.

For the group under study, we concluded that mean values of TST, BM, LM, percentage of sleep stages and AHI were normal for this age range; the low SEf and the high number of arousals and SC characterized a major sleep fragmentation in these individuals; the prevalence of mixed syndrome was 9.5%; there was a high percentage of TST with hemoglobin saturation under 90% (T₉₀); PaO₂ and PaCO₂ correlated with T₉₀; AHI correlated with REMHR; spirometric and polysomnographic variables did not correlate significantly.

Received for publication on 8/18/02

Accepted after revision on 11/6/02

*This study is part of the Master's Dissertation "Description and analysis of spirometric, gasometric and polysomnographic variables of patients with chronic obstructive pulmonary disease" approved on June 16, 2001 by the Health Sciences School of the Universidade de Brasília. Supervisor: Professor Carlos Alberto Assis Viegas.

• 1.Trask CH, Cree EM. Oximeter studies on patients with chronic obstructive emphysema, awake and during sleep. N Engl J Med 1962; 266:639-42.
• 2.Pierce AK, Jarrett CE, Werkle G, Miller WF. Respiratory function during sleep in patients with chronic obstructive lung disease. J Clin Invest 1966;45:631-6.
• 3.Coccagna G, Lugaresi E. Arterial blood gases and pulmonary and systemic arterial pressure during sleep in chronic obstructive pulmonary disease. Sleep 1978;1:117-24.
• 4.Douglas NJ, Calverley PMA, Leggett RJE, Brash HM, Flenley DC, Brezinova V. Transient hypoxemia during sleep in chronic bronchitis and emphysema. Lancet 1979;1:1-4.
• 5.George CF, West P, Kryger MH. Oxygenation and breathing pattern during phasic and tonic REM in patients with chronic obstructive pulmonary disease. Sleep 1987;10:234-43.
• 6.Phillipson EA, Sulivan CE, Read DC. Ventilatory and waking response to hypoxia in sleeping dogs. J Appl Physiol 1978;44:512-20.
• 7.Bye PT, Issa F, Berthon-Jones M, Sullivan CE. Studies of oxygenation during sleep in patients with interstitial lung disease. Am Rev Respir Dis 1984;129:27-32.
• 8.Perez-Padilla R, West P, Lertzman M, Kryger MH. Breathing during sleep in patients with interstitial lung disease. Am Rev Respir Dis 1985; 132:224-9.
• 9.Phillipson EA, Kozar LF, Rebuck AS, Murphy E. Ventilatory and waking response to CO2 in sleeping dogs. Am Rev Respir Dis 1977;115:251-9.
• 10.Berthon-Jones M, Sullivan CE. Ventilation and arousal response to hypoxia in sleeping humans. Am Rev Respir Dis 1982;125:632-9.
• 11.Calverley PM, Brezinova V, Douglas NJ, Catterall JR, Flenley DC. The effect of oxygenation on sleep quality chronic bronchitis and emphysema. Am Rev Respir Dis 1982;126:206-10.
• 12.Shepard JW, Garrison MW, Grither DA, Dolan GF. Relationship of ventricular ectopy to nocturnal oxygen desaturation in patients with chronic obstructive pulmonary disease. Am J Med 1985;78:28-34.
• 13.Moore-Gillon JC, Cameron IR. Right ventricular hypertrophy and polycythemia in rats after intermittent exposure to hypoxia. Clin Sci 1985; 69:595-9.
• 14.Fitzpatrick MF, Mackay T, Whyte KF, Allen M, Tam RC, Dore CJ, et al. Nocturnal desaturation and serum erythropoietin: a study in patients with chronic obstructive pulmonary disease and in normal subjects. Clin Sci 1993;84:319-24.
• 15.Boysen PG, Block AJ, Wynne JW, Hunt LA, Flick MR. Nocturnal pulmonary hypertension in patients with chronic obstructive pulmonary disease. Chest 1979;76:536-542.
• ¹⁶
  16.Resolução 01/88. Artigo 7 inciso II e Art 13. Conselho Nacional de Saúde, Min Saúde; 1988.
• 17.Carskadon MA, Rechtschaffen A. In: Kryger MH, Roth T, Dement WC. Principles and practice of sleep medicine. Philadelphia: WB Saunders Company, 2000;1336p.
• 18.Britsh Thoracic Society. BTS Guidelines for the management of chronic obstructive pulmonary disease. Thorax 1997;52(Suppl 5):S1-S28.
• 19.The National Lung Health Education Program. Strategies in preserving lung health and preventing COPD and associated diseases. Chest 1998;113(Suppl 2):123S-154S.
• 20.Martinez D. Práticas da medicina do sono. São Paulo: Fundo Editorial Byk, 1999;276p.
• 21.Carskadon MA, Rechtschaffen A. In: Kryger MH, Roth T, Dement WC. Principles and practice of sleep medicine. Philadelphia: WB Saunders Company, 2000;1336p.
• 22.Iren T, Gualberto BC. In: Reimão R. Sono. Estudo abrangente. São Paulo: Editora Atheneu, 1996;442p.
• 23.Pollak CP. Daily sleep reports and circadian rest-activity cycles of elderly community residents with insomnia. Biol Psychiatry 1992;32:1019-27.
• 24.Hla KM, Young TB, Bidweell T, Dalta M, Skatrub JB, Dempsey J. Sleep apnea and hypertension. A population-based study. Ann Intern Med 1994;120:382-8.
• 25.Guilleminaut C, Cumminski J, Motta J. Chronic obstructive airflow disease and sleep studies. Am Rev Respir Dis 1980;122:397-406.
• 26.Fletcher EC, Gray BA, Levin DC. Nonapneic mechanisms of arterial oxygen desaturation during rapid-eye movement sleep. J Appl Physiol 1983;54:632-9.
• 27.Catterall JR, Douglas NJ, Calverley PMA, et al. Transient hypoxemia during sleep in chronic obstructive pulmonary disease is not a sleep apnea syndrome. Am Rev Respir Dis 1983;128:24-9.
• 28.Tavares P. Oxigenoterapia a longo termo e sono em pacientes com doença pulmonar obstrutiva crônica [tese]. Rio de Janeiro: Universidade Federal do Rio de Janeiro, 1992;129p.
• 29.Chaouat A, Weitzenblum E, Krieger J, Tfoundza T, Oswald M, Kessler R. Association of chronic obstructive pulmonary disease and sleep apnea syndrome. Am J Respir Crit Care Med 1995;151:82-6.
• 30.Phillipson EA. Control of breathing during sleep. Am Rev Respir Dis 1978;118:909-39.
• 31.Hudgel DW, Martin RJ, Johnson B, et al. Mechanics of the respiratory system and breathing pattern during sleep in normal humans. J Appl Physiol 1984;56:133-7.
• 32.Ballard RD, Clover CW, Suh BY. Influence of sleep on respiratory function in emphysema. Am J Respir Crit Care Med 1995;151:945-51.
• 33.McNicholas WT, Fitzgerald MX. Nocturnal deaths among patients with chronic bronchitis and emphysema. Br Med J 1984;289:878.
• 34.American Academy of Sleep Medicine. Sleep related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 1999;22:667-89.
• 35.Camarinha RP. Estudo correlativo entre variáveis espirométricas e gasométricas em pacientes portadores de doença pulmonar obstrutiva crônica [dissertação]. Brasília: Universidade de Brasília, 1993; 128p.

Publication Dates

• Publication in this collection
  23 June 2003
• Date of issue
  Apr 2003

History

• Accepted
  11 June 2002
• Received
  18 Aug 2002