Screening of liver disease in alpha-1 antitrypsin deficiency (AATD) is usually carried out with liver enzymes, with low sensitivity. We conducted a multicenter cross-sectional study aiming to describe the utility of transient elastography for the identification of liver disease in patients with AATD. A total of 148 AATD patients were included. Among these, 54.7% were Pi*ZZ and 45.3% were heterozygous for the Z allele. Between 4.9% and 16.5% of patients had abnormal liver enzymes, without differences among genotypes. Liver stiffness measurement (LSM) was significantly higher in Pi*ZZ individuals than in heterozygous Z (5.6 vs. 4.6 kPa; p = 0.001). In total, in 8 (5%) individuals LSM was >7.5 kPa, considered significant liver fibrosis, and ≥10 kPa in 3 (1.9%) all being Pi*ZZ. Elevated liver enzymes were more frequently observed in patients with LSM > 7.5 kPa, but in 5 out of 8 of these patients all liver enzymes were within normal range. In patients with AATD, the presence of abnormal liver enzymes is frequent; however, most of these patients do not present significant liver fibrosis. Transient elastography can help to identify patients with liver fibrosis even with normal liver enzymes and should be performed in all Z-allele carriers to screen for liver disease.

Early, mild and young COPD concepts are not clearly defined and are often used interchangeably to refer to the onset of the disease. Objective: To describe and compare the characteristics of mild, young and early COPD in a large sample of COPD from primary and secondary care. Methods: Pooled analysis of individual data from four multicenter observational studies of patients with stable COPD (≥40 years, FEV₁/FVC < 0.7, smoking ≥ 10 pack-years). Mild COPD was defined as FEV₁% ≥ 65%; young COPD as <55 years; and early COPD as <55 years and smoking ≤ 20 pack-years. The relationship between FEV₁(%), age and pack-years was analyzed with linear regression equations. Results: We included 5468 patients. Their mean age was 67 (SD: 9.6) years, and 85% were male. A total of 1158 (21.2%) patients had mild COPD; 636 (11.6%) had young COPD and 191 (3.5%) early COPD. The three groups shared common characteristics: they were more frequently female, younger and with less tobacco exposure compared with the remaining patients. Early COPD had fewer comorbidities and fewer COPD admissions, but no significant differences were found in ambulatory exacerbations. In linear regression analysis, the decline in FEV₁(%) was more pronounced for the first 20 pack-years for all age groups and was even more important in younger patients. Conclusions: Mild, young and early COPD patients were more frequently women. The steepest decline in FEV₁(%) was observed in individuals <55 years and smoking between 10 and 20 pack-years (early COPD), which highlights the importance of an early detection and implementation of preventive and therapeutic measures.

Introduction: Chronic obstructive pulmonary disease is associated with increased lung and systemic inflammation. As part of a multicenter, international study, we aimed to identify associations between easy-to-obtain blood biomarkers and frequency and severity of exacerbations. Methods: Cross-sectional and multicentre study performed in four centers in Spain, Italy, Bulgaria and Slovenia. Patients with COPD according to GOLD criteria were included and blood samples were obtained for blood cells, C-reactive protein (CRP), alpha-1 antitrypsin and fibrinogen. A multivariate stepwise logistic regression model was performed to identify laboratory parameters associated with history of exacerbations. Results: A total of 355 patients were included (mean age 66 years (SD=8.9) and 64% male). Mean FEV1% was 55% (SD=20%) and mean CAT 15.6 (SD=7.9). 208 patients presented ≥1 exacerbation in the previous year, of them 121 (58%) required hospitalization. Patients with exacerbations had only higher CRP (p=0.007), but those with hospitalizations had a higher platelet count (p=0.031) and platelet/lymphocyte ratio (p=0.031), lower hemoglobin (p=0.017) and lower eosinophil/basophil ratio (p= 0.013). Neutrophil to lymphocyte ratio was also higher but not significantly. However, in multivariate analysis only lower FEV1% was identified as independently related to previous exacerbations (OR=0.970, p=0.012). Conclusion: Only CRP was higher in patients with exacerbations, but several routine blood biomarkers were significantly increased in patients who suffered hospital admissions. However, multivariate analysis identified FEV1 as the only significantly associated variable to previous exacerbations.

AATD is characterised by the misfolding and intracellular polymerization of mutant AAT protein within hepatocytes. Polymers can also be found in peripheral blood after secretion into circulation. This was a cross-sectional study to analyse the relationship between CP and lung and liver disease in patients with AATD. Patients with mixed phenotypes of AATD, COPD without AATD and healthy controls were included. To quantify CP, a sandwich ELISA was performed using the 2C1 monoclonal antibody against AAT polymers. Sociodemographic data, clinical characteristics, and liver and lung parameters were collected. A cohort of 117 individuals was recruited: 32(27%) ZZ(11 on augmentation therapy);29(25%) Z-heterozygous;16(14%) with at least one S allele;5(4%) rare variants; and 35(30%) MM. ZZ patients had higher CP(p<0.001) than other phenotypes. ZZ also had higher levels of liver stiffness measurements (LSM) than the remaining AATD patients (p<0.05). ZZ and Z-heterozygous non-augmented patients were classified into 4 groups according to lung(FEV1/FVC=0.7); and liver impairment(LSM < and > =6kPa). Two patients with lung and liver impairment had the highest concentrations of CP(47.5 µg/ml), followed by liver abnormality only (n=6, CP=34µg/ml), lung only (n=18, CP=26.5µg/ml) and no abnormalities(n=23, CP=14.3µg/ml). Differences were highly significant (p=0.004). Non-augmented ZZ and Z-patients with impaired lung function and increased liver stiffness presented higher levels of CP than other clinical phenotypes. Therefore, CP may help to identify patients at higher risk of developing lung and liver disease and may provide some insight into the mechanisms of disease.

Introduction: Currently there are no blood biomarkers to identify patients with PF secondary to COVID-19 pneumonia. The ELF score is a panel of serum markers of liver fibrosis; however, it has also been used in PF. We analyse the ELF score as a serum biomarker of PF due to COVID-19 pneumonia. Methods: Pilot study performed in a random sample of patients recovered from COVID-19 pneumonia. Chest computed tomography (CT) scan and lung function tests (LFTs) at 3 months after discharge were collected. Data were analysed according to ELF scores and posteriorly divided into tertiles: T1<9.3, T2 ≥9.3 - <9.9 and T3 ≥ 9.9. Results: 138 patients were analysed, of whom 85.4% presented bilateral pneumonia. At 3 months after discharge, chest CT scans were available in 132 patients from which 59% still presented abnormal findings and 23% presented impaired LFTs. Globally, the most frequent radiological finding was ground glass opacities (50%), followed by bronchial thickening (27.3%), reticular pattern (20.5%), consolidation (12.1%) and air bronchogram sign in 6.8% of patients. Regarding ELF scores, differences were only observed in T3, with a reticular pattern as main radiological finding (p<0.005). Moreover, patients with both radiological and LFT impairment, presented higher levels of ELF compared with patients with only radiological or LFTs impairments, or no impairment (9.93 (0.77) vs 9.56 (0.82), 9.15 (1.1) and 9.33 (0.74), p<0.023). Conclusion: Patients with both radiological and LFTs alteration at 3 months after COVID-19 pneumonia, had higher levels of ELF. The ELF score might be useful to identify patients who will develop PF after COVID-19 pneumonia.