Content uploaded by Felip Burgos
Author content
All content in this area was uploaded by Felip Burgos
Content may be subject to copyright.
CORRESPONDENCE
Physiological changes in respiratory
function associated with ageing
To the Editor:
We read with interest the review of JANSSENS et al. [1]
entitled "Physiological changes in respiratory function asso-
ciated with ageing", more specifically the subheading devoted
to changes in arterial oxygenation and ventilation-perfusion
(V ©/Q ©) relationships. Although the seminal study of W
AGNER
et al. [2] was addressed in full, it was a shame that they did not
discuss the more recent comprehensive work of our group in
this field [3]. We extensively investigated the distributions of
V ©/Q © ratios in 64 healthy individuals aged 18±71 yrs. The
principal findings of that study were: 1) that V ©/Q © imbalance,
but not increased intrapulmonary shunting, did increase with
age as previously expected; 2) that the increase over the span
of ~50 yrs was physiologically very small; 3) that most of the
variance in V ©/Q © mismatch in this cohort of subjects was not
due to ageing and remained unsettled; and 4) that the fall in
arterial partial pressure of oxygen (PO
2
) with age was also
quite small but was internally consistent with the V ©/Q ©
changes measured independently.
V ©/Q © relationships were characterized in most of these
healthy individuals by narrow distributions that widened
slightly with age together with a trivial shunt of <1% of the
cardiac output in 90% of cases. Both the second moments
(dispersions) of pulmonary blood flow (Log SDQ) and of
alveolar ventilation (Log SDV) increased by ~0.1 between
20±70 yrs. Accordingly, the dispersion of pulmonary perfu-
sion (Log SDQ) increased from 0.36±0.47, akin to a decrease
of oxygen tension in arterial blood (P
a,O
2
)ofonly~6mmHg.
Only 10% of the total variance was attributed to age. A similar
amount was due to intrasubject variability, but none was due
to variations in other factors, such as forced expiratory volume
in one second (FEV
1), FEV1/forced vital capacity (FVC)
ratio, weight or height. We did not measure closing volume
and it is therefore likely that age could disturb V ©/Q ©
matching as a result of increases in closing volume. However,
since the latter mechanism is highly unlikely to influence V ©/
Q © relationships in young healthy individuals [4], and since
the variance of the dispersion of pulmonary blood flow was as
large amongst the subset of young as that of old individuals,
we would postulate that increased closing volume is not a
determinant factor of the variance in V ©/Q © homogeneity.
R. Rodriguez-Roisin*, F. Burgos*, J. Roca*, J.A.
Barbera
Á
*, R.M. Marrades*, P.D. Wagner
#
Servei de Pneumologia i Al.le
Â
rgia Respirato
Á
ria, Dept de
Medicina, Institut d©Investigacions Biome
Á
diques August Pi i
Sunyer (IDIBAPS), Hospital Clõ
Â
nic, Universitat de Barce-
lona, Barcelona, Spain. Dept of Medicine, University of
California, San Diego, La Jolla, CA, USA. Fax: 34 93
2275404.
References
1. Janssens JP, Pache JC, Nicod LP. Physiological changes in
respiratory function associated with ageing. Eur Respir J
1999; 13: 197±205.
distributionsof ventilation-perfusion ratios in normal subjects
breathing air and 100% O
2
. J Clin Invest 1974; 54: 54±68.
3. Cardu
Â
s J, Burgos F, Dõ
Â
az O, et al. Increase in pulmonary
ventilation-perfusion inequality with age in healthy indivi-
duals. Am J Respir Crit Care Med 1997; 156: 648±653.
4. Buist AS, Ghezo H, Anthonisen NR, et al. Relationship
between the single-breath N
2
test and age, sex and smoking
habit in three North American cities. Am Rev Respir Dis
1979; 120: 305±318.
To the Editor:
With great interest, we read the review article by JANSSENS
et al. [1] concerning physiological changes in respiratory
function associated with ageing. The authors have summar-
ized in the abstract that "Physiological ageing of the lung is
associated with dilatation of alveoli, enlargement of air-
spaces, decrease in exchange surface area and loss of
supporting tissue for peripheral airways ("senile emphyse-
ma"), changes resulting in decreased static elastic recoil of
the lung and increased residual volume and functional
residual capacity". Although the functional and structural
alterations of the respiratory system with ageing were sophi-
sticatedly described in the article, we are not in agreement
with the authors that physiological ageing of the lung is
determined as the senile emphysema.
Because the airspace enlargement including ductectasia
and loss of elastic recoil of the lung are commonly inves-
tigated in aged humans without noxious insults [2±4], V
ERBE-
KEN
et al. [5, 6] proposed that the structural and functional
characteristics caused by isolated airspace enlargement seen
in the elderly as "senile lung (ageing lung)", were differen-
tiated from senile emphysema by the absence of alveolar
wall destruction. The ductectasia and airspace enlargement
without alveolar wall destruction was quantitatively assessed
by morphometric indices, e.g. mean linear intercept (MLI)
and destructive index (DI), while the loss of lung elastic
recoil was assessed by the left-sided shifts of pressure-vol-
ume curves of lungs and by the exponential equivalent K [7].
However, it is difficult in human lungs to separate the true
age effect, i.e., the physiological ageing effect, from the
cumulative environmental effects, i.e., the combination of
physiological and pathological ageing effects, since the hu-
man respiratory system is open to the environment, continu-
ously exposing the lung to a variety of pollutants. Although
senescence-accelerated mouse (SAM) is a good model to
investigate the differences between physiological ageing of
the lung, i.e., ageing lung or senile lung, and pathological
ageing of the lung, i.e., cigarette smoke-related airspace
enlargement [7±10], it has been reported that aged mice
under protected circumstances using a filter cage do not ex-
hibit the airspace enlargement or alveolar wall destruction
[11]. In contrast, several canine studies revealed that long-
term exposure to air pollutants at ambient levels might cause
bronchitis lesions and emphysematous lesions in dogs [12].
In humans, it has been suggested that cutaneous hypersensi-
tivity to common aeroallergens is a significant independent
predictor of subsequent decline of lung function among
middle-aged and older males with no history of asthma [13].
M
EYER et al. [14] also reported that neutrophil migration and
Eur Respir J 1999; 14: 1454±1457
Printed in UK ± all rights reserved
Copyright
#
ERS Journals Ltd 1999
European Respiratory Journal
ISSN 0903-1936
low-grade inflammation existed in lower airways of many
clinically normal, older individuals. These results indicate
that long-term exposure to environmental pollution during
life-time, rather than age, plays an important role in the
development of airspace enlargement in later life. Thus, phy-
siological ageing should be named the senile lung or ageing
lung. "Senile emphysema" may be a condition of patholo-
gical ageing of the lung, since emphysema increases in
frequency with age and is found most frequently in patients
in the seventh decade [3, 15].
S. Teramoto, T. Matsuse, Y. Ouchi
Correspondence: S. Teramoto, Dept of Geriatric Medicine,
Faculty of Medicine, Tokyo University Hospital, 7-3-1-Hongo
Bunkyo-ku, Tokyo 113-8655, Japan. Fax: 81 358006530.
References
1. Janssens JP, Pache JC, Nicod LP. Physiological changes in
respiratory function associated with ageing. Eur Respir J
1999; 13: 197±205.
2. Chan ED, Welsh CH. Geriatric respiratory medicine. Chest
1998; 114: 1704±1733.
3. Thurlbeck WM. Chronic airflow obstruction. In: Pathology
of the lung. Thurlbeck WM, Churg AM, eds. New York,
Thieme Medical Publishers Inc., 1995; p.780±825.
4. Teramoto S, Matsuse T, Fukuchi Y, Ouchi Y. Influence of age
on the structure and function in respiratory system: special
reference to aged women. In: Facts, Research, and Inter-
vention in Gerontology. Kaiser FE, Nourhashemi F, Bertiere
MC, Ouhci Y, eds. Toulouse, France, Serdi Publisher, 1998;
pp. 145±155.
5. Verbeken EK, Cauberghs M, Mertens I, Clement J, Lau-
weryns JM, Van de Woestijne KP. The senile lung: com-
parison with normal and emphysematous lungs: 1. structural
aspects. Chest 1992; 101: 793±799.
6. Verbeken EK, Cauberghs M, Mertens I, Clement J, Lau-
weryns JM, Van de Woestijne KP. The senile lung: compa-
rison with normal and emphysematous lungs: 2 functional
aspects. Chest 1992; 101: 800±809.
7. Teramoto S, Fukuchi Y, Uejima Y, Teramoto K, Oka T,
Orimo H. A novel model of senile lung: senescence-acc-
elerated mouse (SAM). Am J Respir Crit Care Med 1994;
150: 234±244.
8. Teramoto S, Fukochi Y, Uejima Y, Teramoto K, Orimo H.
Biochemical characteristics of senescence-accelerated mouse
(SAM). Eur Respir J 1995; 8: 450±456.
9. Teramoto S, Uejima Y, Oka T, et al. Effects of chronic
cigarette smoke inhalation on the development of senile lung
in senescence-accelerated mouse. Res Exp Med 1997; 197:
1±11.
10. Teramoto S, Fukuchi Y. Age-dependent changes in lung
structure and function in the senescence-accelerated mouse
(SAM): SAM-P/1 as a new model of senile hyperinflation of
lung. Am J Respir Crit Care Med 1997; 156: 1361.
11. Kawakami M, Paul JL, Thurlbeck WM. The effect of age on
lung structure in male BALB/cNNia inbred mice. Am J Anat
1984; 170: 1±21.
12. Heyder J, Takenaka S. Long-term canine exposure studies
with ambient air pollutants. Eur Respir J 1996; 9: 571±584.
13. Gottlieb DJ, Sparrow D, O©Connor GT, Weiss ST. Skin test
reactivity to common aeroallergens and decline of lung
function. The Normative Aging Study. Am J Respir Crit Care
Med 1996; 153: 561±566.
14. Meyer KC, Rosenthal NS, Soergel P, Peterson K. Neutrophils
and low-grade inflammation in the seemingly normal aging
human lungs. Mech Ageing Dev 1998; 104: 169±181.
15. Teramoto S, Fukuchi Y. Bullous emphysema. Curr Opin
Pulm Med 1995; 2: 90±96.
From the authors:
We read with interest the comments made by Rodriguez-
Roisin et al. as to the age-related changes in ventilation-
perfusion ratio (V ©/Q ©) heterogeneity and the implication of
increased closing volume (CV) as a possible explanation for
increased V ©/Q © heterogeneity in older healthy subjects.
Rodriguez-Roisin et al. refer to an excellent study analys-
ing, by the multiple inert gas technique changes in pulmo-
nary V ©/Q © inequality with age in 64 healthy individuals
aged 18±71 yrs [1].
The observation that the decrease in oxygen tension in
arterial blood (P
a,O
2
) with ageing is small is indeed consistent
with the observations of G
UE
Â
NARD et al. [2] and DECLAUX et
al. [3] who did not find any significant correlations between
age and changes in P
a,O
2
and suggest that normal values for
P
a,O
2
are in the range of 11.261.0 kPa (8467.5 mmHg;
mean6
SD) in healthy elderly subjects, which is well above
results obtained by previously published regression equa-
tions [4].
However, we have a few comments on the assertion that
increased CV is not a determinant factor in increased V ©/Q ©
heterogeneity in the elderly and on the data on which Rodri-
guez-Roisin et al. base their assumption: 1) The study referr-
ed to includes 64 patients of a mean age of 37614 yrs
(mean6
SD); only our subjects (6%) are aged $60 yrs, the eld-
est being 71 and only 10 subjects are aged $55 yrs (15%).
These data are there-fore hardly representative of the physio-
logical changes in the respiratory system of elderly subjects,
which were the focus of our review [5]; 2) the proportion of
subjects with low V ©/Q © areas (>0.75% of cardiac output) is
75% for the small number of subjects aged $60 yrs (n=4),
versus 6.7% for those aged <60 yrs, suggesting an increase in
V ©/Q © mismatch in these "young" elderly subjects, although
this was not statistically significant; 3) the CV increases with
age; however, data published by L
EBLANC et al. [6] suggest
that the CV may equal the functional residual capacity (FRC)
only when subjects reach ~65 yrs of age (FRC - CV = 1.95 -
(0.036age (yrs)): in younger subjects, the increase in clos-
ing volume may not have a significant repercussion on V©/Q©
homogeneity; 4) the increase in CV with ageing is most
probably not linear; the increase in CV is accelerated after
the age of 50 yrs, and follows a curvilinear (exponential)
equation (DN
2
(%
.
L
-1
) = 0.85 +
e
0.0929 6 age - 6.302); this
emphasizes the importance of studying a large group of older
subjects to document the interaction between CV and V ©/Q ©
mismatch [7]; 5) C
RAPO et al. [8] suggests that the age-
associated anatomo-pathological modifications in small and
distal airways, which may affect and increase the CV, be-
come physiologically significant in much older individuals
than those studied by C
ARDUS et al. [1].
Based on available data, we believe therefore that in-
creased CV cannot presently be excluded as an explanation
for V ©/Q © mismatch in the old and very old; the answer to
this problem will necessitate studies similar to that published
by C
ARDUS et al. [1] including a larger population of older
subjects. Information extrapolated from studies including
younger adults may not reflect the physiological changes
which occur in the very old.
We agree with T
ERAMOTO et al. that the homogeneous
enlargement of alveolar ducts and airspaces, without signs of
inflammation or destruction described in our review [5]
should be considered as "senile lung" and not as "senile
emphysema". Whether the appearance of the characteristic
parenchymal alterations of the "senile lung" is related to a
low grade inflammation in the distal airways, as a reaction to
environmental pollutants, or is just the result of "wear and
tear" alterations in the collagen and elastin framework, warr-
ants further studies.
1455CORRESPONDENCE
J.P. Janssens*, J.C. Pache
+
, L.P. Nicod
#
.
*Dept of Geriatrics,
+
Division of Pathology and
#
Division of
Lung Diseases, Geneva University Hospital, Route de Mon-
Ide
Â
e, 1226, Tho
Ã
nex, Geneva, Switzerland. Fax: 41 223056115
References
1. Cardus J, Burgos F, Diaz O, et al. Increase in pulmonary
ventilation-perfusion inequality with age in healthy indivi-
duals. Am J Respir Crit Care Med 1997; 156: 648±653.
2. Gue
Â
nard H, Marthan R. Pulmonary gas exchange in elderly
subjects. Eur Respir J 1996; 9: 2573±2577.
3. Delclaux B, Orcel B, Housset B, Whitelaw WA, Derenne J.
Arterial blood gases in elderly persons with chronic obstruc-
tive pulmonary disease (COPD). Eur Respir J 1994; 7: 856±
861.
4. Hertle F, Georg R, Lange H. Die arteriellen Blutgaspart-
ialdru
È
cke und ihre Beziehungen zu Alter und anthropo-
metrischen GroÈssen. Respiration 1971; 28: 1±30.
5. Janssens JP, Pache JP, Nicod LP. Physiological changes of
respiratory function associated with ageing. Eur Respir J
1999; 13: 197±205.
6. Leblanc P, Ruff F, Milic-Emili J. Effects of age and body
position on "airway closure" in man. J Appl Physiol 1970;
28: 448±451.
7. Sixt R, Bake B, OxhoÈj H. The single-breath N
2
test and
spirometry in healthy non-smoking males. Eur J Respir Dis
1984; 65: 296±304.
8. Crapo RO. The aging lung. In: Pulmonary disease in the
elderly patient. Mahler DA, ed. New York, USA, Marcel
Dekker Inc., 1993: pp. 1±21.
Postural drainage techniques and gas-
tro-oesophageal refkux in infants with
cystic fibrosis
To the Editor:
Recently PHILLIPS et al. [1] added to the body of knowledge
relating to gastro-oesophageal reflux (GOR) in cystic fibrosis
(CF). I noted with interest the high incidence of GOR (73%)
found in their study of 11 children with CF of <2.5 yrs. This
reinforces the sentiment that GOR is an important issue that
needs to be considered in the management of young children
with CF.
In their article, P
HILLIPS et al. [1] state that "holding the
baby: head downwards positioning for physiotherapy does
not cause gastro-oesophageal reflux". This is different to the
findings of three independent studies on this topic over the
past fifteen years [2±4]. I would like to comment on some of
the significant differences between the studies that may have
contributed to their different results and conclusions.
We studied 20 infants of <5.6 months newly diagnosed
with CF. Eighteen of the infants were <3 months, 15 of those
were #2 months; the other two were 4.4 and 5.6 months [4].
This large group of very young infants with CF is different to
the group of 11 infants and toddlers with CF aged up to 27
months of P
HILLIPS et al. [1].
They chose six positions, of which two positions were 208
head down lying on the left and right side and two positions
were 158 head down lying on the left and right side, both with
a quarter turn towards supine (the other two positions were
horizontal and head up). We studied four positions: supine
horizontal, prone with 30 head-down tilt and lying on the left
and right side with 308 head-down tilt. We studied those four
studied those four positions as they were what we were using
and teaching the parents of infants with CF at our clinic.
I noted with interest that the widely prescribed prone with
head down tilted position [5] was not included in the study of
P
HILLIPS et al. [1]. FOSTER et al. [2] found a mean oesophageal
pH of 2.8 during chest physiotherapy in the prone position in
their study of ten children with CF. The prone position was
associated with the lowest mean pH of the four standard
positions that they studied.
In considering the title of the study of P
HILLIPS et al. [1], I
was puzled by their acknowledgement that "in some infants it
is possible that the head-down tipped positions may worsen
GOR. Therefore, individual evaluation of physiotherapy is
recommended for infants undergoing lower oesophageal pH
monitoring in whom clearance of excess secretions is indi-
cated". Does this suggest that some of the 11 patients with CF
may have had episodes of GOR during chest physiotherapy?
What the study of P
HILLIPS et al. [1] may imply is that, first,
by excluding the prone head-down tilted position and reduc-
ing the angle of head-down tilt, the likelihood of increasing
episodes of reflux is reduced. Secondly, the older the infant
with CF, the lower the likelihood of increased episodes of
GOR during chest physiotherapy. Whether the prone position
should be used for infants with CF, by how much we need to
decrease the angle of head-down tilt and at what age in
infancy and early childhood GOR during chest physiotherapy
becomes less of an issue is open to debate and further
research.
Newborn screening has resulted in the commencement of
daily chest physiotherapy in very young infants (often ~6±8
weeks of age) at many centres. There is substantial evidence
that there is a high incidence of gastro-oesophageal reflux in
infants with cystic fibrosis. I, therefore, believe that when pre-
scribing a chest physiotherapy regimen for infants with cystic
fibrosis, the unique infant differences compared to older pa-
tients should be considered, and further longer-term research
should be undertaken. The main objective is to provide chest
physiotherapy for infants with cystic fibrosis that is optimally
effective in terms of promoting clearance of pulmonary sec-
retions and that does not have iatrogenic effects. In the words
of O
RENSTEIN [6] "Respiratory disease may also provoke reflux
more indirectly by prompting the use of therapies that provoke
reflux. These therapies include . . . postural drainage.
B.M. Button
Physiotherapy Dept, The Alfred Hospital, P.O. Box 315,
Prahran, Victoria 181, Australia. Fax: 61 393491289.
From the authors:
We thank B.M. Button for showing interest in our study.
There are a number of reasons for the discrepancies between
our own [1] and previous studies [2±4]. In their abstract,
FOSTER et al. [2] conclude that chest physical therapy may
precipitate gastro-oesophageal reflux (GOR), but they do not
state whether the subjects were tipped; one position described
is "upright". V
ANDENPLAS et al. [3] investigated physiotherapy
using head-downwards positioning; however, each treatment
lasted 30 min and included the intermittent use of abdominal
thrusts and tracheal rubs to stimulate coughing. It is docu-
mented that the control subjects also suffered regurgitation
and vomiting during "physiotherapy". B
UTTON et al. [4] com-
pared a "standard" physiotherapy regimen (SPT) using tipped-
down positions with a "modified" regimen (MPT) excluding
all tipped postures. They concluded GOR was increased in the
SPT but not with the MPT, but, as T
AYLOR and THRELFALL [7]
1456 CORRESPONDENCE
pointed out, there was no significance difference in reflux
indices between the regimens, and, in the head-downwards
positions, acid refluxate was cleared faster.
In clinical practice, we assess each infant to determine
which segments of the lungs need clearing before treating. We
ensure, however, that, during the course of a day, all lobes are
treated and thus, in our study design, we included the lingula
and middle lobes, which other studies have not. The lateral
segments of the lower lobes were treated; prone head tilted
down was not indicated. Regarding the exact angle of head-
downwards tip in this age group, physiotherapy is most
frequently performed by parents/carers with the infant on a
pillow on the knees. The legs of the adult carer are positioned
to allow different tipped positions. No previous study
describes how the angle of tip was attained or indeed how
it was precisely maintained. Nor, in clinical practice, is it
likely to be measured by busy mothers in a home setting.
As with other studies, our own contains relatively small
numbers of children. In the group we studied, there was no
evidence that the head-down tipped position induced gastro-
oesophageal reflux in any infant. However, neither we nor
anyone else can exclude the possibility that there may be
individuals who were not in the study in whom this is not the
case. Our study does not "imply" anything; we concluded that,
in patients of this age, using standard techniques for chest
physiotherapy, head-down tilt does not cause gastro-oeso-
phageal reflux; indeed, it is in the sitting postural drainage
position that gastro-oesophageal is most likely. These postural
changes are compatible with physiological understanding. We
agree that extrapolation outside the specific conditions and
subjects of any study should be performed with caution, and
certainly what is needed is high quality research-based evid-
ence with proper statistical analysis, rather than mere "beliefs"
and "words".
G.E. Phillips, S.E. Pike, M. Rosenthal, A. Bush
Dept of Paediatric Respiratory Medicine, Royal Brompton
and Harefield Hospital Trust, Sydney Street, London SW3
6NP, UK. Fax: 44 2073518763.
References
1. Phillips GE, Pike SE, Rosenthal M, Bush A. Holding the
baby: head downwards positioning for physiotherapy does
not cause gastro-oesophageal reflux. Eur Respir J 1998; 12:
954±957.
2. Foster AC, Voyles JB, Murphy SA. Twenty four hour pH
monitoring in children with cystic fibrosis: association of
chest physiotherapy to gastro-oesophageal reflux. Paediatr
Res 1983; 17: 188A.
3. Vandenplas Y, Diericx A, Blecker U, Lanciers S, Deneyer M.
Oesophageal pH monitoring data during chest physiotherapy.
J Paediatr Gastroenterol Nutr 1991; 13: 23±26.
4. Button BM, Heine RG, Catto-Smith A, Pheland PD, Olin-
sky A. Postural drainage and gastro-oesophageal reflux in
infants with cystic fibrosis. Arch Dis Child 1997; 76: 148±
150.
5. Physiotherapy in the Treatment of Cystic Fibrosis (CF). Inter-
national Physiotherapy Group for Cystic Fibrosis Mucovis-
cidosis Association 1995. (Available from A. Ramos via email:
aramos.fq@vlc.servicom.es.)
6. Orenstein SR. Respiratory complications of reflux disease in
infants. In: Stein MR, ed. Gastrooesophageal reflux disease
and airway disease. In: Lenfant C, exec.ed. Lung biology in
health and disease. Vol. 129: New York: Marcel Dekker,
1999: 269±284.
7. Taylor CJ, Threlfall D. Postural drainage techniques and
gastro-oesophageal reflux in cystic fibrosis. Lancet 1997;
349: 1567±1568.
1457CORRESPONDENCE
