Upper respiratory disease and qualitative studies in primary ciliary dyskinesia.

Lam, Yin Ting (2023). Upper respiratory disease and qualitative studies in primary ciliary dyskinesia. (Unpublished). (Dissertation, University of Bern, Faculty of Medicine, Faculty of Science and the Vetsuisse Faculty)

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Background: Primary ciliary dyskinesia (PCD) is a rare disease affecting multiple organs with an
estimated prevalence of 1: 10,000. Over 50 genes cause structural or functional changes in motile
cilia, which are crucial for mucociliary clearance. Half of the patients have laterality defects, other
manifestations can include retinitis pigmentosa, hydrocephalus, cystic kidneys, multiple spleens or
fertility issues. Most commonly patients have chronic symptoms of the upper and lower airways.
With such heterogenous clinical presentation, diagnosing PCD is particularly challenging. Most
studies so far focused on diagnostics or pulmonary disease. Symptoms of the ear, nose and throat
(ENT) have been understudied, although ENT symptoms are typically present at birth in patients with
PCD. We do not know the frequency of ENT disease and possible risk factors.
Research is usually driven from the researcher’s perspective. The perspective of patients with PCD is
unknown. We do not know what research priorities they consider important for PCD, nor do we
know in what extent treatment burden affects them and what factors might reduce their burden.

Aims: The overall aim of my PhD was to improve understanding of this rare disease in two neglected,
understudied areas: ENT disease and patient perspectives. Specifically, I aimed to 1) assess the
prevalence of physical activity, respiratory physiotherapy practices and nutritional status of people
with PCD in Switzerland to gain experience with analysing data, while setting up the prospective ENT
cohort for the ENT studies with the aims to 2) to study sinonasal symptoms and examination
findings, and identify possible risk factors for increased sinonasal disease; 3) to assess the correlation
between patient- and parent-reported symptoms, and objective measurements in patients with PCD;
4) study association between upper and lower symptoms, explore association of chronic
rhinosinusitis (CRS) with pulmonary symptoms and lung function. To understand patients’
perspectives beter I aimed to 5) explore patients’ research priorities for PCD and their experience
with 6) treatment burden to identify factors, which might reduce treatment burden to design
appropriate interventions and improve treatment strategies.

Methods: For aim 1), I used data from the first Swiss survey, which was nested in the Swiss PCD
registry. For the ENT aims 2) – 4), I used data from the new cohort I set up with my supervisor, the
ENT prospective international cohort for patients with PCD (EPIC-PCD). We have 13 participating
centres from 10 countries across Europe with over 500 participants enrolled. For aims 5) and 6) each
I am conducting mixed methods studies: phase 1 – qualitative semi-structured interviews with
patients or parents of children with PCD, phase 2 – based on interview results, developing a survey
on patients’ research priorities to circulate worldwide via support groups and on treatment burden
circulated in the Swiss PCD registry.

Results: This thesis includes 6 manuscripts (2 published, 1 submited, 1 mature draft, 1 with
preliminary results, 1 with preliminary results of phase 1):

Manuscript 1: Over half of the participants were physically active, adults saw a professional
physiotherapist less often, as did participants who were regularly active.

Manuscript 2: Chronic nasal problems were the most common symptoms. Nasal polyps,
hypertrophic turbinates, deviated septum and facial pain were found more commonly in adults than
children. The only characteristic associated with higher risk of sinonasal disease was age 10 years and
older.

Manuscript 3: We found no correlation between patient-reported sinonasal symptoms and relevant
clinical examination findings. Otologic symptoms correlated poorly or weakly with otoscopy and
audiometry findings, with age and centre identified as determinants of agreement.

Manuscript 4: Shortness of breath was associated with reported nasal symptoms and ear pain of any
frequency, often or daily hearing problems, headache when bending and with CRS, regardless of
presence of polyps. Sputum production was associated with daily reported, hearing problems, and
CRS. We did not find any association between CRS and FEV1.

Manuscript 5: Main priorities from interviews were development of a cure or restoration of cilia
function and increasing knowledge in different fields such as mental health, treatment burden,
fertility and ENT problems, impact of environment and lifestyle. Quantitative, preliminary results
showed similar priorities, which were finding a cure, research on life expectancy and long-term
disease impacts, health-related behaviours, ENT disease and associations with lung problems. Other
priorities were involving more doctors and people in PCD research, raising awareness of the
condition, followed by mental health, fertility, and treatment burden.

Manuscript 6: Preliminary results of interviews about treatment burden included treatment
duration, financial and administrative burden from health insurance, and reduced quality of life.
In addition to these 6 manuscripts, I contributed as a co-author to 9 manuscripts, which are all
published, except of one that is in revision. They are included as related publications in this thesis. I
am a co-author of at least 6 more manuscripts in preparation.

To conclude: 1) Patients with PCD in Switzerland are physically active and might replace
physiotherapy with sports. 2) Sinonasal disease persists throughout life, likely progresses with age
more nasal polyps and anosmia present in adulthood. 3) Patient-reported symptoms and ENT
examination findings do not correlate. ENT examination should take place regardless of symptoms
complaint. 4) Upper and lower airways disease do not occur independently. It needs to be assessed
as a common entity, using appropriate clinical and patient-reported measures, and to be managed in
unison to improve clinical outcome. 5) Patients’ research priorities focus on developing a cure or
treatment to reduce symptoms. 6) Patients need to manage daily treatment burden in many forms,
particularly adults, who have to battle with symptoms, treatments and administrative burden.

Item Type:	Thesis (Dissertation)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)
Graduate School:	Graduate School for Cellular and Biomedical Sciences (GCB)
UniBE Contributor:	Lam, Yin Ting, Goutaki, Myrofora, Spycher, Ben
Subjects:	600 Technology > 610 Medicine & health 300 Social sciences, sociology & anthropology > 360 Social problems & social services
Language:	English
Submitter:	Doris Kopp Heim
Date Deposited:	22 Sep 2023 12:49
Last Modified:	22 Sep 2023 12:49
Additional Information:	Doctor of Medicine and Philosophy (MD, PhD)
URI:	https://boris.unibe.ch/id/eprint/186513