The Role of Non-pharmacological Rehabilitation Within Pulmonary Sarcoidosis: The Role of Physical Activity and Diet Within Pulmonary Sarcoidosis
Conditions: Sarcoidosis, Sarcoidosis, Pulmonary, ILD, Interstitial Lung Disease
Sponsor: Kingston University

Title Page 
Study Protocol and Statistical Analysis Plan  
Title: The role of physical activity and diet within Pulmonary Sarcoidosis  
Ethics Code: NCT03336736    
Date submitted: 07/11/2017 
 
 
 
 

Research Plan and Protocol  
Background Rationale  
Sarcoidosis is a non-caseating granulomatous disease (Morand et al., 2015), a 
condition that involves the inflammation of organs and tissues (NHS, 2013). The 
granulomas form as a result of lymphocytes cells (Loke et al., 2013) clustering together 
(National institute of Health, 2013a). Up to 90% of sarcoidosis cases are pulmonary, 
however the condition can affect numerous other locations, such as, the liver and heart 
and affects the skin in 25% of cases (Saidha et al., 2012). Pulmonary sarcoidosis 
prevalence is second only to asthma in young adults for respiratory diseases 
(Morgenthau & Iannuzzi, 2011). Sarcoidosis affects 1 in 10,000 in the UK (NHS, 2013) 
with limited research into almost every aspect of the disease.  
Physical activity has frequently been suggested as beneficial for sarcoidosis patients 
(NHS, 2015a). This is due to a host of specific and non-specific benefits to those with 
the condition. This includes the overall improvement to health including decreased 
levels of non-communicable diseases as well as lower the risk of depression (NHS, 
2015b). Although anyone can suffer from depression, sarcoidosis patients have been 
shown to have increased levels (Hinz et al., 2012). In addition, physical activity helps 
not only to slow and stop deconditioning; a major issue within sarcoidosis (Fleischer 
et al., 2014), but also aids the reversal of this process (Strookappe et al., 2015). 
However, the condition lacks specific guidelines, unlike similar conditions such as 
COPD and asthma (ACSM, 2014; National Institute of Health and Care Excellence 
(NICE), 2016). Due to this, sarcoidosis patients are often given advice on exercise and 
other forms of physical activity such as walking or dancing that are not underpinned 
by research specific to their condition and as such are potentially dangerous exercise 
programmes/advice. Holland et al. (2015) states the unique presentation of ILD, 
including sarcoidosis, requires modifications of exercise prescription for individuals, 
which was noted as a key issue by Strookappe et al. (2016) in a systematic review of 
physical activity and training in Sarcoidosis. In addition to this, the effect of pulmonary 
sarcoidosis on exercise capacity and strength in comparison to a healthy population 
is limited and needs further research. Reductions to both exercise capacity and muscle 
strength indicated by lower results than normative values, are known primary 
symptoms of Sarcoidosis (Spruit, 2005; Hildebrand et al., 2012; Baughman, 2013), 

which continue to get progressively worse with the onset of secondary symptoms such 
as deconditioning (Mitchell et al., 2012; Fleischer et al., 2014). The symptoms of 
sarcoidosis, in tandem with the varied manifestations (Skin, liver, heart etc. (Saidha et 
al., 2012)) of the disease alongside pulmonary, make it incredibly hard for accurate, 
suitable suggestions for physical activity, especially when considering the current lack 
of literature. This is highlighted by the role of fatigue within sarcoidosis, which is 
recognised as a major factor within the disease (Baughman, 2013) and therefore 
needs considering when creating an exercise prescription plan.  
Therefore, increased understanding of the effects of pulmonary sarcoidosis is needed 
as well as comparison to a healthy age matched control population to allow for the 
data to be compared alongside other intestinal lung diseases (ILD). Further research 
into this area is vital as exercise training has been shown to be in some cases just 
as/more effective than medical treatment across a wide range of chronic conditions 
(Pedersen & Saltin, 2015). Marcellis et al. (2013) argues rehabilitation should be 
utilised alongside any pharmacological treatment despite the need for future research 
on potential benefits. Strookappe et al. (2016) also states further random controlled 
trials are needed but the effects of physical training seem promising from the current 
limited research.  
Despite Sarcoidosis affecting a significant number of people globally, being second 
only to asthma in young adults for respiratory diseases (Morgenthau & Iannuzzi, 
2011), there is a short supply of research into the condition as well as novel treatments 
to alleviate the primary and secondary symptoms. Therefore therapies (diet and 
physical activity) are required to help the condition but also prevent further reductions 
in QOL.  
Aim: The primary aim of this study is to ascertain the physical activity patterns and 
baseline parameters in those with pulmonary sarcoidosis with regards to perceived 
physical activity and actual physical activity. The secondary aim of the study is to 
investigate the effect of pulmonary sarcoidosis in relation to muscle strength and 
exercise capacity against physical activity, lung function and oxygen saturation and 
how these differ from healthy normative values.  
Primary Outcome: Daily physical activity measures against self-reported (IPAQ). 
Secondary Outcome: Demographic data and clinical status (age, gender & ethnicity); 

Body fat percent, Lung function (forced vital capacity), functional exercise capacity 
assessed by six-minute walk test, muscle strength by isokinetic dynamometer and 
hand dynamometer. Patient reported health status and pulmonary complaints 
objectified in disease-specific quality of life: Sarcoidosis Health Questionnaire and 
fatigue score (Fatigue Assessment Scale (FAS).  
Participants  
Participants with medically diagnosed pulmonary sarcoidosis will be selected. They 
will be recruited through support groups and online forums from the known sarcoidosis 
population. A diagnosis of sarcoidosis will be accepted provided the participant has 
diagnosed pulmonary sarcoidosis ascertained by self-reporting. Patients will be 
prospectively recruited following new diagnosis of non-cardiac sarcoidosis. (1 in 
10,000 have sarcoidosis of which 90% is pulmonary). Due to lack of research into 
sarcoidosis, there is not enough evidence to permit accurate power calculations, 
however, based on previous studies and the proportion of diagnosed cases, n=15 
participants will be aimed for and act as a pilot for a larger randomised control trial 
(power 0.80 [80%], significance P<0.05) excluding drop-out. 
Inclusion Criteria:  
- Patients with known Sarcoidosis according to ATS/ERS/ WASOG criteria statement 
- Age: 18-65 years - Both males and females  
- Written informed consent is obtained.  
- Access to a computer with Internet  
Exclusion Criteria:  
- Contraindications to (not able to perform) physical tests or exercise testing - e.g. 
unstable cardiovascular disease, oncological, cardiac, neurological or orthopedic 
history making them unable to participate screened by a sub-maximal fitness 
screening form.  
- An injury in the past 6 months that inhibits ability to perform exercise testing by a 
submaximal fitness screening form.  
- Patients with a concurrent and predominant diagnosis of another significant 
respiratory disorder (for example: asthma, chronic obstructive pulmonary disease 
(COPD), cystic fibrosis, or lung cancer) by a sub-maximal fitness screening form.  

- Pregnancy  
– Physical disability (non-ambulatory patient e.g. wheelchair or bed-bound)  
- Inability to obtain informed consent  
- Cognitive failure making them unable to give consent or understand questionnaires 
or instruction.  
Experiment Design  
This is a prospective cross-sectional observational project, with no intervention. 
Observational exercise testing will include endurance exercise and muscle strength. 
Patients participating in this study will be treated according to current guidelines 
(ATS/ERS/ WASOG). As such, diagnostic procedures or treatment will not be 
postponed or impacted on by participation in this study. All data will be self-reported 
and self-referred for voluntary participation. Participants will be invited to attend the 
laboratory for testing on two occasions to measure physical activity, fatigue, aerobic 
fitness and muscular strength with exercise testing at the Human Performance lab, 
Kingston University, London to establish the influence on symptoms, physiological and 
psychological outcomes. Exercise testing will follow standard guidelines (ACSM, 
2016). Travel cost reimbursement will be offered to all participants who attend lab 
visits.  
Appropriate health and risk stratification screening will be performed via a sub-
maximal exercise screening form (appendix XI) and any participant with an injury in 
the past 6 months or a known contraindication (ACSM, 2014) to exercise will be 
excluded from the study. Inclusion criteria are based on having pulmonary sarcoidosis, 
aged 18 years or above, and participants may have other forms too but must have 
pulmonary sarcoidosis.  
1. During the two laboratory visits to the Human Performance Lab, patients reported 
response will be objectified by three standardized questionnaires (IPAQ, SHQ and 
FAS), pulmonary function tests, mass and stature laboratory data will be recorded.  
2. The patient is asked to keep a daily record physical activity by wearing a triaxial 
accelerometer on their hip to measure daily physical activities and ambulatory 
movements for 7 days.  

Lab Procedures  
During visit one, participants will sign informed consent forms (appendix II) and have 
any questions answered before continuing. They will then be put through a screening 
process beginning with physical examination: characteristics such as anthropometric 
data (stature, mass, heart rate (HR), blood pressure, age, BMI, fat% (Bodpod, 
Cosmed/ Bioelectric Impedance Analysis (BIA), Tanita) will be collected. Following 
this, participants will conduct a lung function test via computer spirometery (Oxycon 
Pro, VIASYS GmbH, Eric Jaeger, Hoechberg, Germany), their predicted results will 
be corrected for ethnicity (Bellamy, 2005) allowing an accurate percentage of lung 
function to be recorded. Caucasian results remain the same, whilst Black-Caribbean 
are decreased by 13% (Bellamy, 2005). Participants will then conduct muscle strength 
testing of key muscle groups using an isokinetic dynamometer (Biodex System 
4,Biodex Corporation, NY, USA); tests include: elbow flexor muscle strength (EFMS), 
quadriceps peak torque (QPT) and hamstring peak torque (HPT). In addition to this 
handgrip strength will also be assessed via handgrip digital dynamometer (Accord 
Medical Products). A minimum rest period of 20 minutes will follow (Vainshelboim et 
al., 2014) based on exercise-based pulmonary rehabilitation research. Heart rate 
(bpm) will be checked at the end of this period and in two minute intervals until HR 
returns to baseline as per ACSM (2014) guidelines. Physical testing will not take place 
until this return to baseline. Following this rest period participants will conduct a six-
minute walk test (6MWT) during the test participants will be measured for Borg rate of 
perceived exertion and Borg Dyspnoea at 2 minute intervals and at completion of the 
test and oxygen saturation levels of participants will be recorded during the 6MWT via 
a portable pulse oximeter. Once the 6MWT has been completed participants will 
complete three questionnaires, the fatigue assessment scale (FAS; De Vries et al., 
2004), international physical activity questionnaire (IPAQ; Ekelund et al., 2003) and 
Sarcoidosis Health Questionnaire (SHQ; Cox et al., 2003). Before leaving, participants 
will be given tri-axial accelerometers (GT3X+ accelerometer, Actigraph), which will be 
used to measure the participants physical activity (PA) for seven days, to establish 
habitual physical activity levels and compare against the results of the IPAQ.  
During the second lab visit, participants will return their accelerometers and follow the 
same pattern of testing from the first visit, excluding the questionnaires (SHQ, FAS & 
IPAQ) and anthropometric information. The order of testing will follow ACSM (2016) 

guidelines therefore strength and aerobic/anaerobic capacity will be first. Alongside 
this, age-matched healthy participants with no known interstitial lung disease (ILD) or 
other condition linked to reduced physical activity will used as a comparison between 
sarcoidosis and healthy populations.  
Statistical analysis  
A mixed model repeated measures analysis of variance (ANOVA) will be utilized, in 
addition to correlations and regressions.