Sleep desaturation and its relationship to lung function, exercise and quality of life in LAM.
ABSTRACT Lymphangioleiomyomatosis (LAM) is characterised by progressive airway obstruction and hypoxaemia in young women. Although sleep may trigger hypoxaemia in patients with airway obstruction, it has not been previously investigated in patients with LAM.
Consecutive women with lung biopsy proven LAM and absence of hypoxaemia while awake were evaluated with pulmonary function test, echocardiography, 6-min walk test, overnight full polysomnography, and Short Form 36 health-related quality-of-life questionnaire.
Twenty-five patients with (mean±SD) age 45±10 years, SpO(2) awake 95%±2, forced expiratory volume in the first second (median-interquartile) FEV(1)(% predicted) 77 (47-90) and carbonic monoxide diffusion capacity, DL(CO) (%) 55 (34-74) were evaluated. Six-minute walk test distance and minimum SpO(2) (median-interquartile) were, respectively, 447m (411-503) and 90% (82-94). Median-interquartile apnoea-hypopnoea index was in the normal range 2 (1-5). Fourteen patients (56%) had nocturnal hypoxaemia (10% total sleep time with SpO(2) <90%), and the median sleep time spent with SpO(2) <90% was 136 (13-201)min. Sleep time spent with SpO(2) <90% correlated with the residual volume/total lung capacity ratio (r(s)=0.5, p: 0.02), DL(CO) (r(s)=-0.7, p: 0.001), FEV(1) (r(s)=-0.6, p: 0.002). Multivariate linear regression model showed that RV/TLC ratio was the most important functional variable related to sleep hypoxaemia.
Significant hypoxaemia during sleep is common in LAM patients with normal SpO(2) while awake, especially among those with some degree of hyperinflation in lung function tests.
- SourceAvailable from: Carlos R R Carvalho[Show abstract] [Hide abstract]
ABSTRACT: Lymphangioleiomyomatosis (LAM) is characterized by exercise performance impairment. Although airflow limitation is common, no previous studies have evaluated the prevalence and impact of dynamic hyperinflation (DH) in LAM. To investigate the dynamic responses during maximal exercise and the prevalence, predictors, and repercussions of DH in LAM. Forty-two patients with LAM performed symptom-limited incremental cycle exercise and pulmonary functions tests (PFTs) and were compared with 10 age-matched healthy women. Dyspnea intensity, inspiratory capacity, oxygen saturation, and cardiac, metabolic, and respiratory variables were assessed during exercise. Patients with LAM also performed a 6-minute walk test (6MWT). Patients with LAM had higher baseline dyspnea, poorer quality of life, obstructive pattern, air trapping, and reduced diffusing capacity of carbon monoxide in PFTs. Although they had the same level of regular physical activity, their maximal exercise performance was reduced and was associated with ventilatory limitation, greater desaturation, and dyspnea. The prevalence of DH was high in LAM (55%), even in patients with mild spirometric abnormalities, and was correlated with airflow obstruction, air trapping, and diffusing capacity of carbon monoxide. Compared with the non-DH subgroup, the patients who developed DH had a ventilatory limitation contributing to exercise cessation on cycling and higher desaturation and dyspnea intensity during the 6MWT. Ventilatory limitation and gas exchange impairment are important causes of exercise limitation in LAM. DH is frequent in LAM, even in patients with mild spirometric abnormalities. DH was associated with the severity of disease, higher dyspnea, and lower oxygen saturation. In the 6MWT, desaturation and dyspnea were greater in patients with DH.American Journal of Respiratory and Critical Care Medicine 06/2012; 186(4):341-8. · 11.04 Impact Factor
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ABSTRACT: Recent studies suggest poor sleep quality in patients with idiopathic pulmonary fibrosis (IPF). However, so far, the impact of IPF-related sleep breathing disorders (SBDs) on survival has not been extensively studied. In a cohort of 31 (24 males) treatment-naïve, newly diagnosed consecutive IPF patients, we prospectively investigated the relationship of SBD parameters such as apnea-hypopnea index (AHI), maximal difference in oxygen saturation between wakefulness and sleep (maxdiff SpO2), and lowest sleep oxygen saturation (lowest SpO2) with clinical (survival, dyspnea, daytime sleepiness), pulmonary function, submaximal (6-min walk test [6MWT]) and maximal exercise variables (cardiopulmonary exercise test [CPET]), and right ventricular systolic pressure (RVSP). Sleep oxygen desaturation exceeded significantly that of maximal exercise (p < 0.001). Maxdiff SpO2 was inversely related to survival, DLCO%, and SpO2 after 6MWT, and directly with dyspnea, AHI, and RVSP. The lowest SpO2 was directly related to survival and to functional (TLC%, DLCO%) as well as submaximal and maximal exercise variables (6MWT distance, SpO2 after 6MWT, peak oxygen consumption/kg, SpO2 at peak exercise), while an inverse association with dyspnea score, AHI, and RVSP was observed. Our findings provide evidence that intermittent sleep oxygen desaturation significantly exceeds that of maximal exercise and is associated with survival in IPF patients. Furthermore, they imply the existence of a link between lung damage and apnea events resulting to the induction and severity of intermittent sleep oxygen desaturation that aggravate pulmonary arterial hypertension and influence IPF survival. A commentary on this article appears in this issue on page 603. CITATION: Kolilekas L; Manali E; Vlami KA; Lyberopoulos P; Triantafillidou C; Kagouridis K; Baou K; Gyftopoulos S; Vougas KN; Karakatsani A; Alchanatis M; Papiris S. Sleep oxygen desaturation predicts survival in idiopathic pulmonary fibrosis. J Clin Sleep Med 2013;9(6):593-601.Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 01/2013; 9(6):593-601. · 2.93 Impact Factor
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ABSTRACT: Restrictive lung disease leads to ventilatory defects and diffusion impairments. These changes may contribute to abnormal nocturnal pathophysiology, including sleep architecture disruption and impaired ventilation and oxygenation. Patients with restrictive lung disease may suffer significant daytime fatigue and dysfunction. Hypercarbia and hypoxemia during sleep may impact progression of lung disease and related symptoms. Little is known about the impact of treatment of sleep disruption on sleep quality and overall prognosis in restrictive lung disease. This review discusses the pathophysiology of sleep and comorbid sleep disorders in restrictive lung diseases including interstitial lung disease, neuromuscular disease, and obesity hypoventilation syndrome.Clinics in Chest Medicine 09/2014; · 2.17 Impact Factor
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Author's personal copy
Sleep desaturation and its relationship to lung
function, exercise and quality of life in LAM
Pedro Medeiros Jra, Geraldo Lorenzi-Filhob, Suzana P. Pimentaa,
Ronaldo A. Kairallaa, Carlos R.R. Carvalhoa,*
aInterstitial Lung Disease Group, Heart Institute (InCor), University of Sa ˜o Paulo Medical School,
Sa ˜o Paulo 05403-900, SP, Brazil
bSleep Laboratory, Pulmonary Division, Heart Institute (InCor), University of Sa ˜o Paulo Medical School,
Sa ˜o Paulo 05403-900, SP, Brazil
Received 6 January 2011; accepted 9 December 2011
Available online 3 January 2012
Six-minute walk test;
Lung function test
Background: Lymphangioleiomyomatosis (LAM) is characterised by progressive airway obstruc-
tion and hypoxaemia in young women. Although sleep may trigger hypoxaemia in patients with
airway obstruction, it has not been previously investigated in patients with LAM.
Methods: Consecutive women with lung biopsy proven LAM and absence of hypoxaemia while
awake were evaluated with pulmonary function test, echocardiography, 6-min walk test, over-
night full polysomnography, and Short Form 36 health-related quality-of-life questionnaire.
Results: Twenty-five patients with (mean ? SD) age 45 ? 10 years, SpO2awake 95%? 2, forced
expiratory volume in the first second (medianeinterquartile) FEV1(% predicted) 77 (47e90) and
carbonic monoxide diffusion capacity, DLCO(%) 55 (34e74) were evaluated. Six-minute walk
test distance and minimum SpO2 (medianeinterquartile) were, respectively, 447 m (411
e503) and 90% (82e94). Medianeinterquartile apnoeaehypopnoea index was in the normal
range 2 (1e5). Fourteen patients (56%) had nocturnal hypoxaemia (10% total sleep time with
SpO2<90%), and the median sleep time spent with SpO2<90% was 136 (13e201) min. Sleep
time spent with SpO2<90% correlated with the residual volume/total lung capacity ratio
(rsZ 0.5, p: 0.02), DLCO(rsZ?0.7, p: 0.001), FEV1(rsZ ?0.6, p: 0.002). Multivariate linear
regression model showed that RV/TLC ratio was the most important functional variable related
to sleep hypoxaemia.
Conclusion: Significant hypoxaemia during sleep is common in LAM patients with normal SpO2
while awake, especially among those with some degree of hyperinflation in lung function tests.
ª 2011 Published by Elsevier Ltd.
* Corresponding author. Tel.: þ55 11 3171 1320; fax: þ55 11 3885 7036.
E-mail addresses: email@example.com, firstname.lastname@example.org (C.R.R. Carvalho).
0954-6111/$ - see front matter ª 2011 Published by Elsevier Ltd.
journal homepage: www.elsevier.com/locate/rmed
Respiratory Medicine (2012) 106, 420e428
Author's personal copy
Lymphangioleiomyomatosis (LAM) is a rare and fatal inter-
stitial lung disease, with an over world incidence ranging
from 1 to 2.5 cases in 1 million. Although the aetiology is
tuberous sclerosis complex (TSC) 2 gene loss of heterozy-
gosis and consequently loss in the balance between
hamartin/tuberin, proteins synthesised by TSC-1/TSC-2 and
extremely important in the regulation of cellular prolifer-
ation and apoptosis. LAM occurs almost exclusively in
women of childbearing age, sometimes with mild symptoms
as dry cough and wheezing which may lead to incorrect
diagnosis of asthma or COPD in no smoking women. The
most typical clinical findings, however, are dyspnoea and
recurrent spontaneous pneumothorax.1e5LAM is charac-
terised by progressive airway obstruction, and forced
expiratory volume in 1 s (FEV1) is the main variable used to
determine disease severity and treatment follow-up.6
Reduced carbon monoxide diffusion capacity (DLCO),
decreased maximal oxygen consumption (VO2max), and
throughout the disease evolution. Although there are no
established medical treatments, reports of anti-hormonal
(GnRH analogue), rapamycin and doxycycline use are
present in the medical literature.1e10
Hypoxaemia during exercise represents one of the first
functional impairments in patients with LAM.3In addition to
physical exercise,11,12sleep may also trigger hypoxaemia.
For instance, patients with chronic obstructive pulmonary
with similar pulmonary functional
impairments (i.e., hyperinflation and reduced DLCO) may
experience hypoxaemia during sleep.13Nocturnal hypo-
xaemia may be associated with sleep efficiency decline,
quality-of-life impairments, and development of pulmonary
hypertension.13e15Nonetheless, to the best of our knowl-
edge, sleep has not been previously investigated in patients
The aim of this study was to evaluate sleep and
nocturnal desaturation in patients with LAM and its relation
to functional capacity, exercise, and quality-of-life vari-
ables in an outpatient population with LAM. We also eval-
uated nocturnal desaturation and its relation to pulmonary
Consecutive women with LAM attending the Pulmonary
Division of the Hospital das Clinicas, University of Sa ˜o
Paulo, Brazil, were prospectively screened from January
2005 to May 2008. Eligible subjects had (1) a diagnosis of
LAM confirmed by surgical lung biopsy reviewed by
pathologists with pulmonary expertise from the Depart-
ment of Pathology of the University of Sa ˜o Paulo Medical
School and (2) clinical stability for at least 4 weeks, defined
by the absence of hospitalisation, antibiotic use, or
increase in dyspnoea. Patients using oxygen due to resting
hypoxia (arterial oxygen saturation <90%), presence of
chylothorax, or pneumothorax were excluded. Medications
and general treatment were not modified during the
protocol evaluation that was performed within an interval
no longer than 8 weeks. Patients who failed to perform all
functional evaluations were further excluded. Written
informed consent was obtained from all subjects, and the
approved the study “Estudo da func ¸a ˜o pulmonar, sono,
exercı ´cio e qualidade de vida de pacientes com linfangio-
leiomiomatose pulmonary” number: 2645.0.015.000-05.
Pulmonary function test (PFT)
Lung volumes, flow rates, and DLCOwere measured using
a computerised system e Collins Plus Pulmonary Function
Testing Systems (Warren E. Collins, Inc., Braintree, MA,
USA) according to international guidelines recommenda-
tions.16,17Post-bronchodilator volumes were registered.
Percentages of predicted values were derived from stan-
dard equations.18,19All tests were done in the same respi-
ratory physiology laboratory under a barometric pressure
around 695 mmHg. Baseline dyspnoea index was used to
evaluate resting dyspnoea.20
Six-minute walk test (6MWT)
Six-minute walk tests (6MWT) were conducted in a 50-m
long flat straight corridor in the outpatient clinic of Hospital
das Clinicas by a respiratory therapist trained in basic life
support. Every patient performed the test according to the
ATS recommendations.21No supplemental oxygen was
used. Distance in metres, continuous oxygen saturation
level, DSpO2(D: initial SpO2? final SpO2), and Borg index
(limbs and dyspnoea) were registered. Predicted distances
were calculated according to reference equations for
All participants underwent a standard overnight poly-
somnography (EMBLA; Flaga hf. Medical Devices, Reykjavik,
Iceland), including electroencephalography, electroocu-
lography, electromyography, oximetry, nasal thermistor,
a cannula for airflow and ribcage and abdominal belts to
detect breathing movements as previously described.23
Apnoea was defined as complete cessation of airflow for
at least 10 s. Hypopnoea was defined as a decrease to less
than 70% of baseline on either inductance plethysmography
channel or nasal cannula airflow, for 10 s or longer and
apnoeaehypopnoea index (AHI) was calculated as the total
number of respiratory events (apnoeas plus hypopnoeas)
per hour of sleep. The AHI cut-off for no obstructive sleep
apnoea (OSA), mild to moderate OSA, and severe OSA was,
respectively, less than 5, 5e15, and more than 15 events
per hour of sleep. Other measures included the magnitude
of nocturnal oxygen desaturations, expressed by minimum
nocturnal SpO2and total time with SpO2less than 90% (time
SpO2 <90%). Clinically relevant nocturnal desaturation was
defined as a fall in SpO2below 90% for at least 10% of total
Sleep desaturation and its relationship to lung function, exercise and quality of life in LAM421
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Echocardiographic images were obtained in the para-
sternal long-axis and short-axis, the apical long-axis, and
the apical 4-chamber view, according to current stan-
dards, by personnel blinded to the results of the poly-
somnography and PFT. Left atrial diameter (LAD), left
ventricle (LV) end-diastolic internal dimension (LVEDD), LV
end-systolic internal dimension, interventricular septal
thickness (IVST), and LV posterior wall thickness (LVPWT)
were determined from M-mode measurements. In addi-
tion, we obtained the LV ejection fraction and LV mass
measurements. Echocardiography was performed accord-
ing to the Brazilian Society of Cardiology Guidelines.25
Ejection fraction lower than 65% and systolic arterial
pulmonary pressure higher than 40 mm Hg were consid-
Each subject completed the Short Form 36 (SF-36)26,27
questionnaire measuring generic health-related quality of
life (HRQL); the baseline dyspnoea and Borg index (BDI)
measuring basal and exercise shortness of breath, respec-
measuring excessive daytime somnolence and risk to OSA,
Continuous variables are presented as mean (SD) or median/
interquartile range (IQR), and categorical variables are pre-
sented as frequency (percentage) except where stated. To
investigate the possible association between oxygen desa-
turation during sleep and functional variables determined
while awake, Spearman correlation coefficients were
calculated between time SpO2<90% on PSG with functional
parameters while awake, including PFTand 6MWT variables.
Rank Sum test where distribution was skewed. Stepwise
multiple logistic regressions were used to select the signifi-
cant predictors for oxygen desaturation. Model assumptions
were assessed by residual plots. Data were analysed with
are two-tailed, and values <0.05 are considered statistically
Demographic and functional characteristics of the
Thirty women were initially evaluated. Five were excluded
because they did not fulfil biopsy review criteria (n Z2),
were using continuous oxygen therapy due to awake
hypoxaemia (nZ 1), and failed to perform all tests (n Z2).
Therefore, a total of 25 patients completed the protocol
(Fig. 1). The time lag between LAM diagnosis and study
evaluation was 2 ?0.8 years. The demographic and func-
tional variables, including pulmonary function test and
6MWTof the population studied are presented in Table 1. At
the time of the study, all but three patients were being
treated with anti-hormonal therapy (GnRH analogue),
which lead to a state of chemical menopause. Patients did
not have hypoxaemia while awake (Table 1), due to the
study design, and the baseline dyspnoea index was in the
normal range [median: 25e75%, interquartile: 3 (2e4)]. As
expected, pulmonary function tests revealed an obstructive
pattern with reductions in predicted FEV1and DLCO. At the
end of the 6MWT, median/IQR Borg dyspnoea was 3
(2e4.5), and 11 patients had developed SpO2 <90%
(mean ? SD e minimal 6MWT SpO277? 7%).
422 P. Medeiros et al.
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Polysomnography findings are summarised in Table 2.
Generally, sleep efficiency, median apnoeaehypopnoea
index (AHI), and AHI in REM were in the normal range. Four
patients had an AHI >5 events/h (mean? SD e AHI
10.2 ? 4.9). Despite the absence of hypoxaemia while
awake and the absence of significant sleep apnoea disorder,
patients frequently had oxygen desaturation (Table 2).
While ventilation and oxygen saturation remained stable
during most of the slow wave sleep phase (S3eS4), desa-
turation was much more common during REM sleep, with
irregular ventilatory pattern, especially during clusters of
eye movements. Figs. 1e5 represent the most common
polysomnography pattern observed among this set of
patients with LAM. Based on oxygen saturation, patients
were stratified into nondesaturators and desaturators
during sleep (Table 3). Nondesaturators and desaturators
were similar regarding age and BMI and had a slightly lower
SpO2 while awake with no statistical significance. In
contrast, desaturators had significantly lower FEV1, DLCO,
final SpO2in 6MWT, and a higher RV/TLC ratio.
Twenty-one patients of the total of 25 performed thoracic
echocardiography. The 4 patients who were not able to
undergo echocardiography, due to transportation limita-
tions, had pulmonary function similar to the median values
of the whole population (data not shown). Left ventricular
ejection fraction was 70 ?6%, and no pulmonary hyper-
tension or LV systolic dysfunction was found in our pop-
ulation (Table 4).
Nocturnal hypoxaemia and relation to functional
FEV1, RV/TLC, DLCO and final SpO2 in 6MWT yielded
significant correlation coefficients to time SpO2 <90%.
Results are summarised in Tables 3 and 4. Multivariate
linear regression model yielded that among these func-
tional covariates RV/TLC was the remaining variable
statistically related to nocturnal sleep hypoxaemia in the
model (Table 5).
Two SF-36 domains (physical and emotional roles) were the
most impaired domains in the whole population. Both had
statistically significant differences and were worse in sleep
desaturators than in nondesaturators (Table 6). The
Epworth Sleepiness Scale (ESS) results yielded that 2
women in both groups presented a score higher than (8:1)
nondesaturators (age 35 and 40), EES (13,17), apnoea index
(5.1 and 4.0); desaturators (age 31 and 36), EES (9,10),
apnoea index (6.0 and 5.5) [no significant statistical
difference was observed p Z 0.74]. Berlin questionnaire did
not yield differences among both groups too.
This is the first study that systematically evaluated sleep in
patients with LAM. Our study conveys several novel find-
ings. First, 56% of the patients had significant nocturnal
hypoxaemia during sleep despite normal oxygen saturation
while awaken. Second, despite the menopause induced by
GnRH analogue treatment, obstructive sleep apnoea was
not common among patients with LAM. Third, nocturnal
hypoxaemia did not correlate with demographic charac-
teristics or awaken SpO2.
Lastly, nocturnal hypoxaemia correlated with pulmonary
function variables, including FEV1, RV/TLC, DLCO, and
minimum SpO2on 6MWT. Multivariate analysis showed that
nocturnal hypoxaemia correlation to RV/TLC ratio was the
most important one.
These findings indicate that nocturnal desaturation is
a much more common problem in clinical practice than
Baseline patient characteristics of the population
FVC (% predicted)
FEV1/FVC (% predicted)
RV/TLC (% predicted)
DLCO(mL/min/mm Hg) (% predicted)
Awaken resting SpO2(%)
Distance walked 6MWT (m)
Distance walked 6MWT (% predicted)
Minimum SpO2, 6MWT (%)
Baseline dyspnoea index
BMI: body mass index; FEV1: forced expiratory volume in one
second; FVC: forced vital capacity; FEV1/FVC: ratio between
FEV1and FVC; RV: residual volume (L); TLC: total lung capacity
(L); RV/TLC: ratio between RV and TLC; DLCO: diffusion capacity
for carbon monoxide (mL/min/mmHg); 6MWT: 6-minute walk
test; and SpO2: transcutaneous oxygen haemoglobin saturation.
Sleep characteristics in the population studied
Total time of sleep (min)
Sleep efficiency (%)
Sleep latency (min)
REM latency (min)
S1 þ S2 (%)
S3 þ S4 (%)
Apnoea index (events/h)
Apnoea e REM (events/h)
% Time SpO2<90% (%)
Time SpO2<90% (min)
S1 þS2: superficial sleep stages; S3þ S4: slow wave sleep
stages; REM: rapid eye movement stage; and time SpO2<90%:
time of sleep with SpO2less than 90%.
Sleep desaturation and its relationship to lung function, exercise and quality of life in LAM423
Author's personal copy
would have been supposed by current outpatient manage-
ment based only on resting PFT and oximetry. The strength
of it is that we consecutively screened an entire LAM
outpatient clinic population with resting, exercise, and
nocturnal oximetry. The majority of patients were not in an
advanced disease stage, and we looked for possible earlier
predictor variables of functional deterioration. Patients
had mild obstructive ventilatory disturbance and moderate
impairment in DLCO, and none of them had severe
analogue induced menopause could be responsible for
increasing sleep apnoea, OSA was a concern for us during
the design of study.31This finding ensured us about the
safety of anti-hormonal treatment in not increasing the
incidence of OSA.
LAM is structurally characterised by gradual replace-
ment of lung parenchyma by thin wall cysts, which func-
impairment and finally hyperinflation detected in lung
function tests. Our set of patients had mild to moderate
obstructive and diffusion disorder, without rest hypo-
xaemia, and nocturnal hypoxaemia was mainly detected
during irregular ventilation presented in REM sleep. There
are several mechanisms underlying nonapnoeic oxygen
desaturation during sleep that may explain why patients
with LAM and without rest hypoxaemia desaturate during
sleep. They include impairments in: functional residual
capacity, ventilatory responses to hypoxia and hyper-
responses, respiratory muscle fatigue, chemical respiratory
S3eS4 regular ventilation.
REM e hypoventilation.
424 P. Medeiros et al.
Author's personal copy
drive, upper airway resistance and also in the position of
baseline saturation values on the oxyhaemoglobin dissoci-
Among the functional variables evaluated, the RV/TLC
ratio was the main variable related to nocturnal sleep
desaturation. For instance, hyperinflation may be directly
related to the impairment in the ventilation to perfusion
ratio that occurs during recumbence in sleep in this set of
patients. It may also intensify hypoventilation, because
tonus is reduced and auxiliary respiratory muscles are
inactivated. Although, we did not measure exhaled CO2,
and therefore were not able to conclude that hypo-
ventilation was the main phenomenon related to nocturnal
sleep desaturation, the respiratory pattern (Figs. 1e4)
hypoventilation might be an important concern in women
with LAM during sleep.
Since sleep had not been properly evaluated in LAM, and
pulmonary function test results in LAM are very similar to
those of COPD, we may infer that there may be some
common physiologic mechanisms. COPD patients desatu-
rate during sleep even in the absence of OSA, and one of
the most important mechanisms is hypoventilation. Several
studies have shown that recurrent transient hypoxaemia
during sleep is frequent in patients with COPD.13e15
Nocturnal hypoxaemia is particularly marked in patients
with “blue and bloated” clinical phenotype and frequently
occurs during REM sleep. The measurement of minute
ventilation with a pneumotachograph and oxygen satura-
tion with pulse oximetry in a group of patients with severe
Transitional ventilatory pattern: S2eREM.
Sleep desaturation and its relationship to lung function, exercise and quality of life in LAM 425
Author's personal copy
COPD demonstrated a nearly 20% lower SpO2during non-
REM sleep and 40% lower oxygenation during REM sleep
than during the awake state, primarily due to reduced tidal
Tidal volume small reductions, with little or no change in
breathing frequency, are present from wakefulness to
NREM sleep reducing alveolar ventilation. This phenomenon
leads to a mild increase in arterial CO2 tension of
2e8 mm Hg, despite a 10e30% fall in metabolic CO2
pronounced during REM sleep, and severe oxygen desatu-
ration especially occurs during bursts of rapid eye move-
ments and might be intensified by the misbalance in
ventilation-perfusion due to recumbence. Since the venti-
latory response to hypoxia decreases by 33% during NREM
sleep many subjects remain asleep with arterial saturation
as low as 70% with no apparent NREMeREM differences.36,37
This mechanism may be responsible for the normal sleep
efficiency found in our group of patients (88%), despite the
fact that they did or did not desaturate during sleep.
In addition, chronic hypoxaemia has been associated
with development of pulmonary hypertension, mainly
through enhancement of prevascular resistance (potassium
channel blockage and intracellular calcium influx) and
misbalance in serotonin and endothelin actions.39Increased
pulmonary arterial pressure has been detected during sleep
in patients with COPD, and pulmonary hypertension and cor
pulmonale are commonly seen in this set of patients.40
Therefore, desaturation during sleep may represent an
important predictor of severity and influence on patients
with LAM quality of life, morbidity, and mortality as in
According to analysis of the questionnaires, we found
that patients with nocturnal desaturation had more limi-
tations in physical and emotional domains than the ones
who did not. Impairments in quality of life related to health
Patient characteristics stratified according to the absence or presence of nocturnal hypoxaemia during sleep.
CharacteristicsDesaturators (n Z14)Nondesaturators (n Z11)
Apnoea index (events/h)
Minimum saturation 6MWTa
97 ? 1
93 ? 4
MNS: minimum nocturnal saturation; BMI: body mass index; FEV1: forced expiratory volume in one second; FVC: forced vital capacity;
RV: residual volume (L); TLC: total lung capacity (L); RV/TLC: ratio between RV and TLC; DLCO: diffusion capacity for carbon monoxide
(mL/min/mmHg); and time SpO2<90%: time of sleep with SpO2less than 90%.
Data are expressed as Median (IQR).
between time SpO2 <90% during polysomnography and
functional and 6MWT variables.
Multivariate analysis e linear regression e
DLCO: diffusion capacity for carbon monoxide (mL/min/mmHg);
FEV1: forced expiratory volume in one second in litres; RV/TLC:
ratio between residual volume in litres and total lung capacity
in litres; MNS: minimum nocturnal saturation; 6MWT: 6-min
walk test; and SpO2: transcutaneous oxygen haemoglobin
tion and functional, exercise, and echocardiographic
Correlations between nocturnal sleep desatura-
0.6 (p Z0.02)
?0.5 (p Z0.02)
0.7 (p Z0.0001)
?0.7 (p Z0.0001)
?0.6 (p Z0.002)
0.5 (p Z0.02)
?0.7 (p Z0.001)
0.6 (p Z0.02)
p<0.05 Wilcoxon test; MNS: minimum nocturnal saturation;
FEV1: forced expiratory volume in one second in litres; DLCO:
diffusion capacity for carbon monoxide (mL/min/mmHg); RV/
TLC: ratio between residual volume in litres and total lung
capacity in litres; 6MWT: 6-min walk test; SpO2: haemoglobin
oxygen saturation; and time SpO2<90%: time of sleep with SpO2
less than 90%. rsZSpearman correlation coefficient.
426P. Medeiros et al.
Author's personal copy
status are certainly multifactorial, and probably architec-
tural sleep disturbance and other variables not evaluated
may influence health perceptions. However, there might be
a direct relation between HRQOL impairment and nocturnal
hypoxaemia, although not precisely demonstrated in other
obstructive populations (COPD), which should make us pay
great attention to this association in patients with LAM.
Our study has limitations that warrant discussion. First,
it is possible that because of our sample size and mild
functional impairments pulmonary hypertension was not
observed and therefore no association with nocturnal
hypoxaemia could be observed. Second, we do not have
data about arterial blood gas either in rest or in exercise,
which would have helped us evaluate respiratory functional
status. Third, although we believe that hypoventilation was
the main mechanism leading to nocturnal hypoxaemia, CO2
levels were not measured during sleep, and so we are not
able to confirm this hypothesis. However, the ventilatory
pattern detected during REM versus NREM sleep may lead us
to hypothesise that this could be an important mechanism
associated with sleep desaturation.
In conclusion, in a survey of a LAM outpatient pop-
ulation, isolated nocturnal desaturation was very common
and was present in more than half of patients. Hyperinfla-
tion was the main functional characteristic related to
nocturnal sleep hypoxaemia. HRQOL impairment was more
frequent among desaturators; physical and emotional roles
were the most disturbed domains. Desaturation was more
intense during sleep than during 6MWT, and patients with
nocturnal desaturation did not have impaired sleep effi-
ciency. Therefore, to stratify LAM severity and understand
its progression, we believe that nocturnal oxygen desatu-
ration during sleep must be investigated and ruled out in all
patients with LAM.
The study was approved by the InCor/Hospital das Clinicas
This study was funded by LIM-09 at the Hospital das Clini-
cas, University of Sa ˜o Paulo Medical School.
Conflict of interest
The authors have no financial or other potential conflicts
ofinterest to disclose.
The authors thank all supporting technicians in the Sleep
and Pulmonary Function Laboratories.
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