Background: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international... Show moreBackground: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history.Methods: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels<11 mu M and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022.Results: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%).Conclusions: EARCO has recruited >1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Show less
This thesis describes the evaluation of pain perception in acute and chronic pain patients and the strength of the endogenous pain modulation system in chronic pain patients. Additionally, pain... Show moreThis thesis describes the evaluation of pain perception in acute and chronic pain patients and the strength of the endogenous pain modulation system in chronic pain patients. Additionally, pain phenotypes are determined in patients with chronic pain. The ability of patients with acute pain after surgery and patients with fibromyalgia to consistently score random painful stimuli on a numerical rating scale is assessed, and the influence of opioids on this ability is evaluated. In patients with fibromyalgia, the offset analgesia paradigm is also evaluated. Offset analgesia is defined as the reduction in pain perception after a small decrease in a nociceptive heat stimulus, that is larger than would be expected from the magnitude of the stimulus decrease. This paradigm can be used to assess the endogenous ability to modulate incoming pain signals. Another manifestation of endogenous pain modulation is conditioned pain modulation (CPM). This is the reduction of pain perception of a nociceptive stimulus by the application of a second nociceptive stimulus on a remote area on the body. In this thesis the ability of a new device specifically developed to induce CPM is evaluated. In the last 2 chapters, the signs and symptoms of chronic pain patients with fibromyalgia, diabetes and sarcoidosis are used to construct 4 pain phenotypes. These phenotypes represent groups with more homogeneous patterns of signs and symptoms, which may be important to identify and evaluate targeted drug therapy. Show less
