Primary ciliary dyskinesia (Siewert's / Kartagener's Syndrome): Respiratory symptoms and psycho-social impact

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Abstract
Although the pathophysiological defect in primary ciliary dyskinesia (PCD; Siewert's/Kartagener's syndrome) is now well characterised, there are few studies of the impact of the condition upon health function, particularly in later life. This study assesses the health impact of the condition in a large group of patients. In addition, it assesses the similarity in age of diagnosis, symptoms and problems of those with situs inversus (PCD-SI) and those with situs solitus (PCD-SS). Postal questionnaire sent to members of the UK Primary Ciliary Dyskinesia Family Support Group. The questionnaire contained the St. George's Respiratory Questionnaire (SGRQ) and the SF-36 questionnaire for assessing health status. 93 questionnaires were returned, representing a 66% response rate. Replies were received from similar numbers of PCD-SI and PCD-SS. Individuals with PCD-SI did not show a significant tendency to be diagnosed earlier, and neither did they show any difference in their symptoms, or the relationship of symptoms to age. Respiratory symptoms were fairly constant up until the age of about 25, after which there was a slow increase in symptoms, and a decline in health status, patients over the age of 40 being about one and a half standard deviations below the mean on the physical component score of the PCS. Patients diagnosed earlier in life, and hence who had received more treatment for their condition, had better scores on the SGRQ Impact and Activity scores. PCD is a chronic condition which has a progressively greater impact on health in the second half of life, producing significant morbidity and restriction of life style. Early diagnosis, and hence earlier treatment, may improve symptoms and the impact of the condition.
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BMC Pulmonary Medicine
Open Access
Research article
Primary ciliary dyskinesia (Siewert's / Kartagener's Syndrome):
Respiratory symptoms and psycho-social impact
I Christopher McManus*
1
, Hannah M Mitchison
2
, Eddie MK Chung
2
,
Georgina F Stubbings
3
and Naomi Martin
3
Address:
1
Department of Psychology, University College London, Gower Street, London WC1E 6BT, UK,
2
Department of Paediatrics and Child
Health, University College London, Gower Street, London WC1E 6BT, UK and
3
Department of Psychology, University College London, Gower
Street, London WC1E 6BT, UK
Email: I Christopher McManus* - i.mcmanus@ucl.ac.uk; Hannah M Mitchison - hmitchis@ucl.ac.uk;
Eddie MK Chung - eddie.chung@ucl.ac.uk; Georgina F Stubbings - lestat_coven@hotmail.com; Naomi Martin - naimartin@hotmail.com
* Corresponding author
Primary ciliary dyskinesiaRespiratory functionSt George's Respiratory QuestionnaireSF-36 questionnairesitus inversus
Abstract
Background: Although the pathophysiological defect in primary ciliary dyskinesia (PCD; Siewert's
/ Kartagener's syndrome) is now well characterised, there are few studies of the impact of the
condition upon health function, particularly in later life. This study assesses the health impact of the
condition in a large group of patients. In addition, it assesses the similarity in age of diagnosis,
symptoms and problems of those with situs inversus (PCD-SI) and those with situs solitus (PCD-SS).
Methods: Postal questionnaire sent to members of the UK Primary Ciliary Dyskinesia Family
Support Group. The questionnaire contained the St. George's Respiratory Questionnaire (SGRQ)
and the SF-36 questionnaire for assessing health status.
Results: 93 questionnaires were returned, representing a 66% response rate. Replies were
received from similar numbers of PCD-SI and PCD-SS. Individuals with PCD-SI did not show a
significant tendency to be diagnosed earlier, and neither did they show any difference in their
symptoms, or the relationship of symptoms to age. Respiratory symptoms were fairly constant up
until the age of about 25, after which there was a slow increase in symptoms, and a decline in health
status, patients over the age of 40 being about one and a half standard deviations below the mean
on the physical component score of the PCS. Patients diagnosed earlier in life, and hence who had
received more treatment for their condition, had better scores on the SGRQ Impact and Activity
scores.
Conclusions: PCD is a chronic condition which has a progressively greater impact on health in
the second half of life, producing significant morbidity and restriction of life style. Early diagnosis,
and hence earlier treatment, may improve symptoms and the impact of the condition.
Background
The condition now known as Primary Ciliary Dyskinesia
(PCD), a case of which was reported by Siewert [1], was
first properly recognised by Kartagener [2,3], who
Published: 27 November 2003
BMC Pulmonary Medicine 2003, 3:4
Received: 29 July 2003
Accepted: 27 November 2003
This article is available from: http://www.biomedcentral.com/1471-2466/3/4
© 2003 McManus et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all
media for any purpose, provided this notice is preserved along with the article's original URL.
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described bronchiectasis, nasal polyposis, and chronic
sinusitis in a group of patients who also showed situs
inversus totalis, the complete left-right reversal of the vis-
cera [4]. Subsequent work by Afzelius [5] demonstrated
that patients with Kartagener's syndrome had a motility
defect in the cilia of respiratory mucosa, in the lungs and
sinuses, and that in addition in males there can also be a
defect of sperm motility, which results in reduced fertility
[6].
Electron microscopy of mucosal cilia and sperm tails
shows that in PCD the normal 9+2 architecture is dis-
rupted due to the absence of dynein arms [7]. Since
dynein is one of the key intra-cellular 'molecular motors'
[7,8], the absence of the dynein arms is responsible for the
impaired motility of the cilia and sperm. The identifica-
tion of the ultra-structural ciliary defect means that it is
now more appropriate to describe the condition as pri-
mary ciliary dyskinesia, the condition resulting from a pri-
mary problem in ciliary motility. The recognition of
ciliary dyskinesia or immotility in Kartagener's syndrome
has resulted in improved diagnosis, and an increasing
awareness that the condition is more frequent than had
been realised, and that, despite being an inherited defect,
it is sometimes only diagnosed quite late in life [9,10].
Although the condition is usually inherited as an auto-
somal recessive [11,12], and some specific gene defects
have been recognised [13,14], it is clear that the syndrome
shows substantial genetic heterogeneity [15]
Although Kartagener's syndrome classically showed situs
inversus, a 'partial' syndrome was also recognised histori-
cally in which all of the symptoms were present, but the
viscera were normally oriented (situs solitus). It is now
clear that such cases are equally as frequent as the full syn-
drome, that cases of the syndrome with or without situs
inversus co-occur within families with an autosomal reces-
sive pattern of inheritance, and that the proper phenotype
is not situs inversus but is more likely to be random situs,
with a 50:50 chance of the viscera showing the normal or
the reversed pattern [16]. Such a model can therefore
explaining the occasional occurrence of monozygotic
twins with PCD, one showing situs inversus and the other
situs solitus [17]. Although the precise causal mechanism
for the development of random situs, has not been fully
elucidated in PCD, work on situs inversus in a range of spe-
cies, including mice, frogs, chicks and zebra-fish [18], sug-
gests that the problem arises during development due to a
ciliary defect in the nodal region (or its homologues of
Hensen's node in the chick, or the Spemann organiser in
amphibia, which are all associated with the protein
known as left-right dynein [19,20]), which results in dis-
rupted or random fluid flow [21,22] – for a semi-popular
account see McManus [23]. There are however some prob-
lems with the theory, and ciliary function may not entirely
explain laterality development [24,25]. Although there is
no direct evidence that patients with PCD also show
defects in the cilia in the nodal region, the simultaneous
occurrence of defects both in 9+2 cilia and 9+0 cilia in
Hfh4 null mice [26], and in mice with the human DNAH5
mutation which occurs in PCD [27], suggests that it is
probably the case.
Despite the structural basis of PCD now being well-under-
stood, there have been few studies of the effects of the
condition on the overall health status of patients
(although there are studies of respiratory function e.g.
[28]). In particular there is no systematic description of
the pattern of respiratory and other symptoms, of their
variability and their development over the life-span, and
neither is there any account of the impact of the condition
on the life-style of the patients, or its effect upon their
mental health. A search of PubMed found 771 articles
using the search term ("Primary ciliary dyskinesia" or
Kartagener*) and 693195 articles using the search term
(Psycholog* or social), but a joint search of these catego-
ries found only a single article, in Spanish, which was only
a case report [29].
The prevalence of PCD in the UK is difficult to estimate
precisely. Although a figure of 1 in 15,000 has been
quoted, which may itself be an underestimate, that would
mean there are about 70 new cases born each year, and
about 3,000 patients in total [4].
Here we describe a study of a group of 93 patients with
PCD who are all members of a Patient Support Group
based in southern England (although patients came from
all over the UK), and in whom respiratory symptoms have
been measured using the St. George's Respiratory Ques-
tionnaire, and health status has been assessed using the
SF-36 questionnaire.
Methods
A postal questionnaire was sent in January 2003 to all
individuals on the mailing list of the UK's Primary Ciliary
Dyskinesia Family Support Group. A reminder was sent to
non-respondents after four weeks.
The questionnaire consisted of 16 pages of A4, and cov-
ered a wide range of topics, not all of which are relevant
to the present study, since a study was also being carried
out of lateralisation [30]. Measures of personality were
also collected, but will be reported elsewhere [31]. Sepa-
rate versions of the questionnaire were provided for adults
and children (under 16 years of age). The principle differ-
ence was in the consent forms (see below), and in addi-
tion there were minor changes of wording between the
two forms, principally to do with work/school, and with
occasional simplification of wording in child version. The
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child version also did not contain questions about
smoking.
Respiratory symptoms were assessed by the St. George's
Respiratory Questionnaire (SGRQ) [32-35], which pro-
vides three separate scales, Symptoms, Activity and
Impact. It has been validated in bronchiectasis [34]. The
scores are scaled in the range 0 – 100, where a score of 100
indicates optimal functioning within the context of respi-
ratory illness.
Health Status overall was assessed by version 2 of the SF-
36 questionnaire, which is a widely used generic instru-
ment for assessing mental and physical functioning [36],
for which UK population norms are also available [37].
The questionnaire has eight sub-scales which can be
divided into two broad groups, Physical Functioning,
Role Physical, Bodily Painand General Health which are
primarily physical, and Energy/vitality, Social function-
ing, Role Emotional and Mental Health which are pri-
marily mental. The eight sub-scales are each scored in the
range 0 – 100, where a score of 100 indicates optimal
functioning. Factor analysis was used in the population-
based survey to calculate weights for deriving two sum-
mary scores, the Physical Component Summary (PCS)
and the Mental Component Summary (MCS) [37].
Unlike the sub-scales, the PCS and MCS are scored so that
in the reference population the mean is 50, and the stand-
ard deviation is 10, meaning that 95% of the population
score in the range 30–70. Separate age and sex-related
norms are also available http://www.hsru.ox.ac.uk/
sf36v2.htm.
The study was approved by the joint UCL/UCLH Commit-
tees on the Ethics of Human Research. The mailing also
included a letter from the secretary of the Support Group
which endorsed the study. In order to protect patient con-
fidentiality, the names of members of the Support Group
were not known to the researchers, address labels being
applied to envelopes by the Support Group. Respondents
were given the opportunity to provide contact details for
further research, and a majority did so. The questionnaire
contained a consent form as an integral part of its con-
struction, and this was signed either by the patient, or,
where appropriate, by the patient and their parent or
guardian.
Results
Response rate
The initial mailing was to 160 addresses. Responses were
received from 93 individuals, and a further 15 envelopes
were returned by the Post Office as undeliverable for one
reason or another. The response rate is therefore 93/(160-
15) = 66%.
Respondents
Ninety-three completed questionnaires were returned,
although not all respondents had replies to all questions
(in some cases because of being too young). Parents of
children were encouraged to respond to the question-
naire, irrespective of how young the child was, and to
complete only those questions which it was possible to
answer for the child. The age distribution was somewhat
skewed, the mean being 22.7 years (SD 16.8), with the
median being 16.5 (quartiles 10.8 and 31.3), and the 10
th
and 90
th
percentiles being 5.4 and 53.7). 59 (63.4%)
respondents were female and 34 were male. The female
respondents were somewhat older (Man-Whitney U test,
p = .039; mean age of females = 25.2; mean age of males
= 18.42) . Of those under the age of 16, 55% (24/44) were
female, but for those over the age of 16, 71% (35/49) were
female. The origin of the difference is not clear.
Situs inversus
48 respondents said that their heart was on the right, and
44 that their heart was on the left (one respondent did not
answer this question). There is therefore no evidence of a
response bias in favour of those with their heart on the
right (χ
2
= 0.17, 1 df=, NS). All of the respondents who
said that their heart was on the right said that this had
been confirmed by X-ray, and all but two said that to their
knowledge all of their body organs were reversed. It there-
fore seems safe to infer that there are 48 cases of Primary
Ciliary Dyskinesia with situs inversus (PCD-SI), 44 cases of
Primary Ciliary Dyskinesia with situs solitus (PCD-SS), and
one of PCD with situs unknown.
Family history
Twenty respondents reported that other members of their
family had PCD. There was no association with situs
inversus, 10 of the 20 having PCD-SI and 10 having PCD-
SS.
Age at diagnosis
Figure 1 shows the age at diagnosis in relation to age at the
time of the survey for the PCD-SI and PCD-SS patients.
The age at diagnosis was slightly lower in the PCD-SI
group (9.1, SD 12.1; median = 5.0, IQR = .62 – 12.0, N =
29) than in the PCD-SS group (mean = 13.8 yrs, SD 16.6;
median = 7.0, IQR = 1.2 – 24.1, N = 30), although the dif-
ference was not significant using either a t-test (t
57
= 1.244,
p = .219) or a Mann-Whitney U-test (z = 1.02, p = .306).
The standard deviation in both groups was however very
large, indicating that most of the older patients had only
been diagnosed relatively recently (on average the
patients over the age of 30 (mean = 46.6, SD 11.9), were
32.1 years old at diagnosis, i.e. mostly diagnosed within
the past fifteen years – see figure 1). Multiple regression of
age at diagnosis, after taking age into account, did find an
almost significant difference between the PCD-SI and
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PCD-SS groups (t
56
= 1.919, p = .060), although the effect
was principally due to the outlier, who was aged 63, but
diagnosed at the age of five. Removal of that case resulted
in a non-significant difference (t
55
= 1.492, p = .141).
Smoking
A question on smoking was only included in the ques-
tionnaire sent to those over the age of sixteen. Two indi-
viduals (4%) were current smokers; both were male and
smoked ten cigarettes per day. A further six (13%) were ex-
smokers, and the remaining 37 (82%) had never smoked.
St. George's Respiratory Questionnaire
The three sub-scales of the St. George's Respiratory Ques-
tionnaire all correlated highly with one another (Symp-
toms with Activity, r = .663, p < .001; Symptoms with
Impact, r = .779, p < .001; and Activity with Impact, r =
.757, p < .001). The Symptoms sub-scale correlated signif-
icantly with age (r = -.479, p < .001), as also did the Activ-
ity sub-scale (r = -.387, p < .001), and the Impact sub-
scale (r = -.401, p < .001). Figure 2 shows a lowess (locally
weighted least-squares) plot of the relationship of the
symptoms sub-scale to age. The Symptom score declines
only very slightly until about the age of 25, after which the
Age at diagnosis of PCD (ordinate), in relation to current age (abscissa), separately for patients with PCD-SI (open circles, dashed line), and PCD-SS (solid circles, solid line)Figure 1
Age at diagnosis of PCD (ordinate), in relation to current age (abscissa), separately for patients with PCD-SI (open circles,
dashed line), and PCD-SS (solid circles, solid line). The fitted lines are lowess curves.
Age
706050403020100
Age at diagnosis
70
60
50
40
30
20
10
0
PCD-R
PCD-L
PCD-SI
PCD-SS
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score declines somewhat more rapidly and there is a
worsening of respiratory symptoms. Although not shown,
the Activity and Impact sub-scales show a similar rela-
tionship with age.
The SF-36 measures of Health Status
Although the eight sub-scales of the St. George's Respira-
tory Questionnaire provide a detailed picture of health
status, the vast majority of the variance in them is more
simply described by the physical component score and
mental component scores. These scores also have the
advantage of well-described population norms. Both the
PCS and the MCS in our sample show a significant corre-
lation with age (r = -.344, p < .001; r = -.363, p < .001
respectively). However the population norms also show a
decline associated with normal ageing, and therefore on
its own this correlation is difficult to interpret. Figures 3
and 4 show scattergrams and lowess curves of the PCS and
MCS in relation to age, and in relation to population
norms for the age ranges 16–24, 25–34, 35–44, 45–54
and 55–64. The lowess curve in figure 3 shows that the
PCS is only about half a standard deviation below the
population mean until the mid-20s, after which the score
declines somewhat more rapidly than the population
norms, and from about the age of 40 or so it is about one
and a half standard deviations below the norms. In con-
trast, although figure 4 shows that the MCS also declines
with age, the declining health status broadly parallels that
found in the general population as a whole, being at most
about one third to one half a standard deviation below
the population norms.
The Symptom scale of the St. George's Respiratory Questionnaire plotted in relation to the age of the respondentFigure 2
The Symptom scale of the St. George's Respiratory Questionnaire plotted in relation to the age of the respondent. PCD-SS
individuals are shown as solid black circles (•) and PCD-SI individuals as open black circles (). The solid black line is the lowess
curve fitted through the data.
0 10203040506070
Age
0
10
20
30
40
50
60
70
80
90
100
St. George's Questionnaire: Respiratory Symptom Scale
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Age at diagnosis in relation to symptoms
An important question concerns the impact of the age at
diagnosis upon symptoms. An earlier diagnosis allows the
possibility of medically based interventions to try and pre-
vent the longer-term complications of the condition. Sta-
tistically the best way to visualise this is in terms of 'time
since diagnosis' (i.e. Current Age minus Age at Diagnosis)
since that is the time during which medical care was pro-
vided. If medical care has an effect upon symptoms, then
time since diagnosis should provide an additional predic-
tor of symptom score, after age has been taken into
account. Table 1 firstly shows the regression of symptom
scores upon age, and then shows the regression of scores
upon age and time since diagnosis (with each effect taking
the other into account). The SF-36 physical and mental
scores, and the SGRQ Symptoms score do not show a sig-
nificant effect of time since diagnosis. However the SGRQ
Impact score shows a statistically significant effect of time
since diagnosis (p = .022), and the regression coefficient
is positive (.580), in contrast to the negative regression
coefficient for age (-.599) – in other words, despite a
decline in score with each year of age, there has been an
increase due to each year of treatment. Furthermore, since
the regression coefficients are unstandardised, and hence
are on the same scale of SGRQ points/year, then the effect
of age, and the effect of time since diagnosis are equiva-
lent, but with opposite signs, suggesting that the two
effects balance one another out so that deterioration has
The Physical Component Score of the SF-36 Health Status measure, plotted in relation to the age of the respondentFigure 3
The Physical Component Score of the SF-36 Health Status measure, plotted in relation to the age of the respondent. PCD-SS
individuals are shown as solid black circles (•) and PCD-SI individuals as open black circles (). The solid black line (-) is the
lowess curve fitted through the data. The dashed black line (- - -) shows the population norm (see text), and the dotted black
lines (.....) show one standard deviation above and below the population norm.
0 10203040506070
10
20
30
40
50
60
SF-36 Physical Summary Score
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The Mental Component Score of the SF-36 Health Status measure, plotted in relation to the age of the respondentFigure 4
The Mental Component Score of the SF-36 Health Status measure, plotted in relation to the age of the respondent. PCD-SS
individuals are shown as solid black circles (•) and PCD-SI individuals as open black circles (). The solid black line (-) is the
lowess curve fitted through the data. The dashed black line (- - -) shows the population norm (see text), and the dotted black
lines (.....) show one standard deviation above and below the population norm.
Table 1: Regression of the effects of age and time since diagnosis upon symptom scores. Column (1) shows the simple regression of
symptom score upon age, without taking time since diagnosis into account.
Effect of age, without taking time
since diagnosis into account (1) b
(SE) Sig
Effect of age, taking time since
diagnosis into account (2) b (SE)
Sig
Effect of time since diagnosis,
taking age into account (3) b (SE)
Sig
SGRQ-Symptoms -.750 (.171) p < .001 -.832 (.191) p < .001 .354 (.363) p = .334
SGRQ-Activity -.500 (.172) p = .005 -.646 (.188) p = .001 .628 (.359) p = .085
SGRQ-Impact -.465 (.121) p < .001 -.599 (.129) p < .001 .580 (.246) p = .022
SF-36: PCS -.292 (.105) p = .007 -.328 (.117) p = .007 .159 (.223) p = .480
SF-36: MCS -.216 (.073) p = .005 -.241 (.082) p = .005 .106 (.156) p = .500
Column (2) shows the regression of symptom score upon age after taking time since diagnosis into account, and column (3) shows the regression
of symptom score upon time since diagnosis after taking age into account. The effects in columns (2) and (3) are therefore statistically independent.
Regression coefficients are shown as the 'b' (unstandardised) coefficients, along with their standard error (SE) and significance levels (p). Entries in
bold have p < .1.
0 10203040506070
20
30
40
50
60
SF-36 Mental Summary Score
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ceased after diagnosis. The effect of time since diagnosis
upon the SGRQ Impact Score is shown in figure 5, a
median split being used to group the patients into those
who have been diagnosed for more than eight years
(mean time since diagnosis = 4.5 years, SD= 2.1; mean age
= 17.2, SD = 16.5) and those who have been diagnosed
less than eight years (mean time since diagnosis = 15.3
years, SD = 8.9; mean age = 25.4, SD = 14.8) . The SGRQ
Activity score shows an effect that is almost significant at
the .05 level (p = .085), and the effect is in the expected
direction (a positive regression coefficient on time since
diagnosis). If a one-tailed test has been used, which seems
reasonable since treatment is expected to benefit symp-
toms, then the effect would have reached the conven-
tional level of significance (p = .042).
PCD-SI compared with PCD-SS
Iindividuals with PCD-SI and those with PCD-SS were
compared on the various measures of symptoms and
health status. Simple t-tests showed no differences
between PCD-SI and PCD-SS, and neither were there
effects of situs on symptoms after taking age into account
using a multiple regression. A detailed table of results is
available from the first author on request.
Other symptoms
Patients with PCD often report a range of other symptoms
including nasal congestion, headache, earache, sinus
pain, sore throat, and heartburn [4,38]. We assessed each
of these by modifying one of the questions of the SGRQ.
Respondents indicated the extent to which the problem
The Impact scale of the St. George's Respiratory Questionnaire plotted in relation to the age of the respondent and the time since diagnosis (calculated as Current Age minus Age at diagnosis)Figure 5
The Impact scale of the St. George's Respiratory Questionnaire plotted in relation to the age of the respondent and the time
since diagnosis (calculated as Current Age minus Age at diagnosis). Individuals with a time since diagnosis of more than eight
years are shown as solid black circles (•), and the lowess curve is shown as a solid black line (-), and those with a time since
diagnosis of less than eight years are shown as open black circles () and the lowess curve is shown as a dashed black line (- -
- -).
0 10203040506070
Age
0
10
20
30
40
50
60
70
80
90
100
St. George's Questionnaire: Impact Scale
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had affected them over the past four weeks, using five
categories: 'Not at all' [scored 0], 'One day or so' [Scored
1], 'A few days a month' [Scored 2]. 'Several days a week'
[Scored 3], or 'Almost everyday' [Scored 4]. Figure 6 shows
that almost all individuals reported "a runny nose and
nasal congestion". "Pain over my sinuses" and "head-
aches" typically affected patients for a few days a month,
whereas "a sore throat" and "indigestion of heartburn
(reflux)" affected patients once a month or so. There was
a tendency for sinus pain, headache and heartburn to
increase with age. "Earache or hearing problems" showed
a more unusual pattern, being very frequent in childhood
and declining through adolescence to a minimum at
about 25 years of age, and then climbing once more in fre-
quency. The 'U'-shaped shape of the age curve for earache
is confirmed using multiple regression by a highly signifi-
cant quadratic effect of age after taking the linear effect
into account (p < .001).
Treatments
Although our study did not have access to clinical records,
we did ask a number of questions about the treatments
that patients used "to help with the symptoms of PCD".
Table 2 summarises the results. A clear majority of
patients, although not all, were currently using physio-
therapy and breathing exercises/techniques, and about
half were taking regular antibiotics and bronchodilators.
The use of expectorants and antacids or other drugs to
help with heartburn or reflux were more common with
increasing age. None of the treatments seemed to be used
more commonly in patients who had been diagnosed
longer ago.
Nasal congestion, sinus pain, headache, sore throat, earache and heartburn in relation to ageFigure 6
Nasal congestion, sinus pain, headache, sore throat, earache and heartburn in relation to age. Symptoms are scored on a scale
of 0 (None) to 4 (almost every day) – see text. A small amount of vertical jitter has been added to data points so that individu-
als are more easily distinguishable. The solid lines are lowess curves.
Age
706050403020100
Nasal congestion
5
4
3
2
1
0
-1
Age
706050403020100
Heartburn
5
4
3
2
1
0
-1
Age
706050403020100
Headache
5
4
3
2
1
0
-1
Age
706050403020100
Earache
5
4
3
2
1
0
-1
Age
706050403020100
Sinus pain
5
4
3
2
1
0
-1
Age
706050403020100
Sore throat
5
4
3
2
1
0
-1
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Page 10 of 12
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An important question concerns the relationship between
treatment usage and symptoms. We therefore carried out
a regression analysis relating symptom measures to the
seven treatments about which we had asked. At the first
step, age and years since diagnosis were entered into the
analysis, and then a forward entry stepwise process was
used to examine the predictive effects of the therapies. The
SGRQ Symptoms score was predicted firstly by Antacids/
Heartburn-Reflux treatments (beta = -.445, p < .001), and
then by use of bronchodilators (beta = -.275, p = .012).
Given the scoring of the treatment measures (high scores
indicate treatment use), and the scoring of the symptom
measures (low scores indicate poorer functioning), the
negative beta coefficients indicate that those taking the
treatments have lower symptom scores than those not tak-
ing them. Broadly similar results were found for the other
outcome measures. The SGRQ Activity score was pre-
dicted firstly by Antacid use (beta = -.469, p < .001), and
then by expectorant use (beta = -.323, p = 016). The SGRQ
Impact score was predicted firstly by expectorant use (beta
= -.450, p < .01), and then by Antacid use (beta = -.301, p
= .010). The SF-36 Physical Components Score was
predicted firstly by Expectorant use (beta = -.461, p =
.001), and then by Antacid use (beta = -.296, p = .024).
Finally, the SF-36 Mental Component Score was predicted
only by Antibiotic use (beta = -.283, p = .037). Mucolytic
use, physiotherapy and breathing exercises were not pre-
dictive of any of the symptom scores after other treat-
ments had been taken into account. It should be noted
that in each of the analyses the beta coefficient is negative,
meaning that those taking the treatment had poorer
health.
Discussion
Primary Ciliary Dyskinesia is a chronic illness, in which,
as Siewert emphasised in his description of the first prop-
erly documented case, symptoms can be present from
soon after birth. Although the symptoms even from birth
are inconvenient, our results suggest that during child-
hood and adolescence there is relatively little impact upon
normal, healthy functioning, the standard measures of the
SF-36 showing little deviation from normality. However
during the mid-20s there is a continual and progressive
increase in respiratory symptoms. Our results using the St.
George's Respiratory Questionnaire, which has been vali-
dated against objective measures of respiratory function
[32-34] are clearly parallel to the decline in respiratory
function with age which was measured by Ellerman and
Bisgaard [28] using standard spirometric techniques. A
replotting of those data (available from the first author),
clearly shows a graph which is parallel in form to that of
our figure 5. The long-term, longitudinal study of Eller-
man and Bisgaard [28] also showed that respiratory func-
tion was significantly worse in patients who presented in
adulthood rather than when the condition was diagnosed
in childhood. As in our results, Ellerman and Bisgaard
[28] also showed that there was little deterioration once
patients were under the supervision of a respiratory clinic,
when management included regular spirometry, daily
physiotherapy and monthly sputum cultures.
As well as lower respiratory symptoms, individuals with
PCD also suffer a range of other symptoms from the ears,
nose and throat, and upper gastrointestinal tract. Of some
interest in our study is the decline in earache through
adolescence, which provides a useful validation of the
Table 2: Treatments used by patients in the study, and the Pearson correlation with age, age at diagnosis and years since diagnosis with
usage (scored 3 = 'At present', 2 = 'In the past' and 1 = 'Never used').
Usage Correlation of usage with:
"Never used" "In the past" "At present" Age Age at diagnosis Years since
diagnosis
Regular antibiotics 10 (11%) 36 (39%) 46 (50%) .042 (NS) .227 (NS) .236 (NS)
Bronchodilators
(inhaler or tablets)
15 (17%) 23 (25%) 53 (58%) .166 (NS) .122 (NS) .008 (NS)
Mucolytics to thin
the sputum
75 (89%) 6 (7%) 3 (4%) .029 (NS) .092 (NS) -.046 (NS)
Physiotherapy 1 (1%) 21 (23%) 69 (76%) -.139 (NS) -.022 (NS) -.174 (NS)
Breathing
exercises and
techniques
11(12%) 13 (14%) 68 (74%) .119 (NS) .228 (NS) -.120 (NS)
Expectorants 64 (73%) 19 (22%) 5 (6%) .409 (p < .001) .420 (p = .001) .176 (NS)
Antacids or other
drugs for
heartburn or
reflux
64 (72%) 16 (18%) 9 (10%) .380 (p < .001) .398 (p = .002) .101 (NS)
BMC Pulmonary Medicine 2003, 3 http://www.biomedcentral.com/1471-2466/3/4
Page 11 of 12
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quality of our data, since such problems are thought to
resolve as the Eustachian tube becomes larger due to
growth. The subsequent resurgence of earache was more
surprising, and requires further exploration.
On the physical scores of the SF-36 in our study there is a
continual decline with age, such that from about the age
of 40 onwards the health status of these individuals is one
to one and a half standard deviations below the popula-
tion mean (although there is substantial variability at all
ages). That is a large and important effect on health, and
although PCD does not usually manifest in an increased
mortality, there is clearly a moderate degree of morbidity
which affects normal physical functioning (although
there seems relatively little effect on social and emotional
functioning beyond the normal effects of ageing).
The results, particularly those shown in figure 3, are
important because they suggest that the morbidity
resulting from PCD is progressive across the life-span, and
hence that early therapeutic interventions may be able to
prevent the deterioration in health that we have found.
The possible benefit of early medical intervention, partic-
ularly on the Impact and Activity scores of the SGRQ, is
suggested by the analyses of table 1, which show that an
earlier diagnosis, which results in more years of treatment
since diagnosis, has a positive impact on symptoms. There
is a need for properly designed, prospective studies both
of early diagnosis itself, and of interventions such as
regular sputum culture, routine use of antibiotics, and
physiotherapy, all which may reduce morbidity [4].
Although earlier diagnosis may contribute to a better clin-
ical outcome, it is not clear from our data what is the main
causative component of that better outcome. We had
basic self-report measures of the treatments received by
these patients, and we looked for correlations with out-
come. Although they were present and highly significant,
in each case the regression coefficients were negative,
meaning that those taking the treatments had poorer
health. The implication is that the treatments taken are a
response to symptoms, rather than that they are having a
positive impact upon them. That is supported by the
majority of the significant effects concerning expectorants
and antacids (which are readily available as non-prescrip-
tion medicines) rather than antibiotics, bronchodilators,
or physiotherapy and breathing exercises, which are more
associated with hospital treatment. That interpretation is
supported by the sole correlate of antibiotic use being
with the SF-36 Mental Component Score, suggesting anti-
biotics can be a response to anxiety and other psycholog-
ical responses by patients to their illness.
Our data represent the largest published study of the
symptoms and effects upon health in PCD, but we are
aware that there is a risk that our sample may be biassed.
All of the subjects are volunteers who had chosen to join
the PCD Family Support Group, so that it is possible
either that our subjects are not representative, perhaps
coming from the more severe end of the spectrum of dis-
ease, or, particularly in the younger patients, their condi-
tion is less severe but parents have chosen to be involved
in the support group in order to have as much informa-
tion as possible about the condition. Although both bias-
ses are possible, they also emphasise the need for properly
representative and systematic studies of patients who are
typical of the entire population. That would also require a
concerted effort to identify a national sample of all indi-
viduals with PCD, independent of symptoms and presen-
tation and diagnosis at clinics.
Many of the subjects in our study are relatively young, in
part reflecting the frequent presentation of patients due to
symptoms in the neonatal period, and the increased
awareness of paediatricians for the diagnosis in young
patients with chronic respiratory or otolaryngological
problems. We encouraged parents to respond on behalf of
their children and with the collaboration of their children,
and were gratified by the response rate. Although there
might be a concern, particularly in children under the age
of ten, that the reports are not reliable, the fact of the mat-
ter is that those under ten report similar patterns of symp-
toms to those in their teens, and that this provides support
and validation of the younger patients' responses. It is also
the case that none of our conclusions would differ if indi-
viduals under the age of ten or twelve or sixteen were elim-
inated from this report.
A striking, and biologically fascinating, aspect of PCD is
that half of the patients have situs inversus (and Siewert
himself was himself impressed by the co-occurrence of the
unusual conditions of bronchiectasis in childhood and
situs inversus). Although it might be expected that the age
at diagnosis would be lower in individuals who had situs
inversus (PCD-SI) than in those with situs solitus (PCD-SS)
the trend in this study did not reach statistical signifi-
cance. The present results are therefore similar to those of
Coren et al [38] who also found a non-significant trend
towards PCD-SI cases being diagnosed earlier than PCD-
SS. Even if a larger series were to find a significant effect,
the broad conclusion has to be that even if the diagnosis
is often triggered by the presence of situs inversus, the exist-
ence of other symptoms, in particular bronchiectasis in
younger patients, should be sufficient to suggest PCD as a
possible diagnosis.
Although only a half of PCD patients have situs inversus,
the rest having the so-called 'partial Kartagener's
syndrome', our analysis makes clear that the symptoms of
PCD-SI and PCD-SS are the same, and the evolution of the
BMC Pulmonary Medicine 2003, 3 http://www.biomedcentral.com/1471-2466/3/4
Page 12 of 12
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condition with age is also the same. The situs inversus that
occurs is therefore independent of the chronic respiratory
symptoms, and therefore the true syndrome, as Afzelius
and others [5] have recognised, is upper and lower respi-
ratory tract problems due to ciliary immotility, coupled
with random situs.
Competing interests
None declared.
Acknowledgments
We are grateful to Carol Polak and the members and the scientific commit-
tee of the PCD Family Support Group for their help with this research, and
to Andrew Bush and Mark Gardiner for helpful discussions.
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