Scientific Concept of the National Cohort (status ... - Nationale Kohorte

A.2
A.2. Scientific background and rationale for study elements
Airway inflammation and deteriorated repair and remodeling processes are major pathophysiological
mechanisms underlying chronic lung diseases. In contrast to respiratory function,
only few noninvasive techniques can provide information about inflammatory processes
in the lung. Among them, only exhaled nitric oxide (NO), FeNO, has gained clinical significance
because upregulation of NO by inflammatory cytokines and mediators in central and
peripheral airways can be monitored in exhaled air. Elevated levels of exhaled NO in asthmatic
individuals are indicative of an ongoing allergic, i.e., mostly eosinophilic inflammation
within central and/or peripheral airways. Therefore, exhaled NO is currently considered as
a supplement to standard clinical asthma care guidelines. When quantified in terms of sensitivity/specificity
and ROC curves, the amount of diagnostic information regarding allergic
airway disorders is comparable to that of nonspecific bronchial challenges or sputum analyses.
Acute respiratory tract infections are also associated with elevated NO concentrations.
Within epidemiologic settings, it is also of interest to identify an allergic component of airway
inflammation in subjects with COPD 207-209 .
Assessment of lung function and preclinical phenotype:
Examinations (at baseline and during reassessment)
Level 1: Spirometry
Level 2: Exhaled NO
MRI program: Lung volume
A.2.3.6 musculoskeletal functions and phenotypes
Osteoarthritis affects about 15-25% of the population over the age of 60, with knees, hands
and hips being the most frequently involved sites 210-212 . The disorder is often highly disabling
and progressive and, indeed, osteoarthritis accounts for most of the total hip and knee replacements
in Germany. Little is known about factors that provoke the manifestation of clinical
symptoms and trigger the patient’s decision to seek medical care. Recent studies indicated a
substantial genetic influence which is site-specific for hip, knee, and hand osteoarthritis and
affects not only the development but also the progression of the disease 212, 213 . The National
Cohort will offer the unique opportunity to investigate the complex interplay among genetic,
environmental, and lifestyle factors in the pathogenesis of osteoarthritis and associated comorbidity
in a prospective manner. Using blood and urine samples from presymptomatic
individuals who develop osteoarthritis later on, particular attention will be paid to identifying
biomarkers for early risk prediction. By combining functional examinations and MRI of hip
and knee joints we can follow changes in function and structure prospectively to search for
subtle MRI markers to predict hip osteoarthritis in the presymptomatic phase and to identify
incident cases of hip and knee osteoarthritis by imaging.
Rheumatoid arthritis has a prevalence of about 0.8% of the adult population 214-217 , and biological
agents to treat rheumatoid arthritis and related inflammatory diseases are on positions
1 and 2 of the 30 drugs with the highest sales volume in Germany 218 . Complex interactions
between environmental (e.g., viral infections) and behavioral factors (e.g., nutrition, smoking)
and the contribution of comorbidity (e.g., metabolic syndrome, CVD) to disease onset and
outcome have been recognized. Chronic inflammation itself, in part accompanied by accelerated
aging of the immune system, is associated with an increased risk for endothelial damage,
CVD, lymphomas, diabetes, and an unfavorable body composition 219-221 . Thus, inflammatory
arthropathy constitutes a confounding factor in studies of chronic disease. Utilizing
the longitudinal design, the National Cohort will evaluate the potential impact of known and
novel biomarkers to predict the development of rheumatoid arthritis during the presymptomatic
stage. Incident cases will be identified mainly through active follow-up. Importantly, a
musculoskeletal examination, including the examination of joints, is planned to be part of the
program (see Sect. A.3.3).
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