Rationale: Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of patients with frequently exacerbating disease are not well described. Objectives: To establish if there is a “frequent exacerbator phenotype” in bronchiectasis and the impact of exacerbations on long-term clinical outcomes. Methods: We studied patients with bronchiectasis enrolled from 10 clinical centers in Europe and Israel, with up to 5 years of follow-up. Patients were categorized by baseline exacerbation frequency (zero, one, two, or three or more per year). The repeatability of exacerbation status was assessed, as well as the independent impact of exacerbation history on hospitalizations, quality of life, and mortality. Measurements and Main Results: A total of 2,572 patients were included. Frequent exacerbations were the strongest predictor of future exacerbation frequency, suggesting a consistent phenotype. The incident rate ratios for future exacerbations were 1.73 (95% confidence interval [CI], 1.47–2.02; P < 0.0001) for one exacerbation per year, 3.14 (95% CI, 2.70–3.66; P < 0.0001) for two exacerbations, and 5.97 (95% CI, 5.27–6.78; P < 0.0001) for patients with three or more exacerbations per year at baseline. Additional independent predictors of future exacerbation frequency were Haemophilus influenzae and Pseudomonas aeruginosa infection, FEV1, radiological severity of disease, and coexisting chronic obstructive pulmonary disease. Patients with frequently exacerbating disease had worse quality of life and were more likely to be hospitalized during follow-up. Mortality over up to 5 years of follow-up increased with increasing exacerbation frequency. Conclusions: The frequent exacerbator phenotype in bronchiectasis is consistent over time and shows high disease severity, poor quality of life, and increased mortality during follow-up.

Idiopathic pulmonary fibrosis (IPF) represents a chronic progressive fibrotic interstitial lung disease of unknown cause with an ominous prognosis. It remains an unprecedent clinical challenge due to its delayed diagnosis and unpredictable clinical course. The need for accurate diagnostic, prognostic and predisposition biomarkers in everyday clinical practice becomes more necessary than ever to ensure prompt diagnoses and early treatment. The identification of such blood biomarkers may also unravel novel drug targets against IPF development and progression. So far, the role of diverse blood biomarkers, implicated in various pathogenetic pathways, such as in fibrogenesis (S100A4), extracellular matrix remodelling (YKL-40, MMP-7, ICAM-1, LOXL2, periostin), chemotaxis (CCL-18, IL-8), epithelial cell injury (KL-6, SP-A, SP-D), autophagy and unfolded protein response has been investigated in IPF with various results. Moreover, the recent progress in genetics in IPF allows for a better understanding of the underlying disease mechanisms. So far, the causative mutations in pulmonary fibrosis include mutations in telomere-related genes and in surfactant-related genes, markers that could act as predisposition biomarkers in IPF. The aim of this review is to provide a comprehensive overview from the bench to bedside of current knowledge and recent insights on biomarkers in IPF, and to suggest future directions for research. Large-scale studies are still needed to confirm the exact role of these biomarkers.

Background: Evidence on the association of leptin and adiponectin and smoking is limited and discordant. Leptin and adiponectin represent the most abundant adipokines in human plasma that play crucial roles in the pathophysiology of metabolic syndrome, atherosclerosis and insulin resistance....

Asthma is generally characterized by variable symptoms such as dyspnea and wheezing and variable airflow obstruction. This review focuses on a subset of patients suffering from asthma with persistent airflow limitation that is not fully reversible (asthma with fixed airflow obstruction, FAO). The pathophysiology, the risk factors and the clinical outcomes associated with FAO are presented, as well as the distinct clinical entity of severe asthma and its inflammatory subtypes (T2 and non-T2). The current strategies for the treatment of these endotypes and treatment of the distinct Asthma/COPD overlap (ACO) phenotype are described. Management and medical interventions in FAO and/or ACO patients demand a holistic approach, which is not yet clearly established in guidelines worldwide. Finally, a treatment algorithm that includes FAO/ACO management based on pharmacological and non-pharmacological treatment, guideline-based management for specific co-morbidities, and modification of the risk factors is proposed.

Background : Anxiety and depression are common psychological disturbances among asthmatic patients. The aim of the present study is the assessment of anxiety and depression in asthmatic patients and their correlation with symptoms control level and number of exacerbations per year. Methods : One hundred patients with asthma diagnosis, according to the Global Initiative for Asthma (GINA), aged > 18 years old, having a stable disease, were included. Emotional status was evaluated using the Hospital Anxiety Depression Scale (HADS). Patients were followed up for a year to assess the number and severity of exacerbations. Results : Most of our patients were female (58%), middle-aged (mean = 54 ± 13), and married (81%), with low frequency of smoking habits (smokers, ex-smokers and non-smokers were 26%, 30% and 37%, respectively) and low levels of both anxiety and depression [median (interquartile range (IQR)) = 4(2) and median (IQR) = 4(2), respectively]. At the low and moderate level of the depression subscale, female patients experienced asthma exacerbations more frequently compared to male patients (adjusted Incidence Rate Ratio (aIRR) = 4.30; 95% Confidence Interval (CI): 1.94–9.53 and aIRR = 1.82; 95% CI: 1.07–3.13, respectively). Conclusions. Clinicians should evaluate asthma patients for depression, as gender differentially influences outcomes among those with low and moderate levels of depression, with female asthmatics presenting more frequent exacerbations.

Background: Coronavirus disease 2019 (COVID-19) has been a pandemic since 2020, and depending on the SARS-CoV-2 mutation, different pandemic waves have been observed. The aim of this study was to compare the baseline characteristics of patients in two phases of the pandemic and evaluate possible predictors of mortality. Methods: This is a retrospective multicenter observational study that included patients with COVID-19 in 4 different centers in Greece. Patients were divided into two groups depending on the period during which they were infected during the Delta and Omicron variant predominance. Results: A total of 979 patients (433 Delta, 546 Omicron) were included in the study (median age 67 years (54, 81); 452 [46.2%] female). Compared to the Omicron period, the patients during the Delta period were younger (median age [IQR] 65 [51, 77] vs. 70 [55, 83] years, p < 0.001) and required a longer duration of hospitalization (8 [6, 13] vs. 7 [5, 12] days, p = 0.001), had higher procalcitonin levels (ng/mL): 0.08 [0.05, 0.17] vs. 0.06 [0.02, 0.16], p = 0.005, ferritin levels (ng/mL): 301 [159, 644] vs. 239 [128, 473], p = 0.002, C- reactive protein levels (mg/L): 40.4 [16.7, 98.5] vs. 31.8 [11.9, 81.7], p = 0.003, and lactate dehydrogenase levels (U/L): 277 [221, 375] vs. 255 [205, 329], p < 0.001. The Charlson Comorbidity Index was lower (3 [0, 5] vs. 4 [1, 6], p < 0.001), and the extent of disease on computed tomography (CT) was greater during the Delta wave (p < 0.001). No evidence of a difference in risk of death or admission to the intensive care unit was found between the two groups. Age, cardiovascular events, acute kidney injury during hospitalization, extent of disease on chest CT, D-dimer, and neutrophil/lymphocyte ratio values were identified as independent predictors of mortality for patients in the Delta period. Cardiovascular events and acute liver injury during hospitalization and the PaO₂/FiO₂ ratio on admission were identified as independent predictors of mortality for patients in the Omicron period. Conclusions: In the Omicron wave, patients were older with a higher number of comorbidities, but patients with the Delta variant had more severe disease and a longer duration of hospitalization.