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A central paradigm of immunity is that interferon (IFN)-mediated antiviral responses precede pro-inflammatory ones, optimizing host protection and minimizing collateral damage 1 , 2 . Here, we report that for coronavirus disease 2019 (COVID-19) this paradigm does not apply. By investigating temporal IFN and inflammatory cytokine patterns in 32 moderate-to-severe patients with COVID-19 hospitalized for pneumonia and longitudinally followed for the development of respiratory failure and death, we reveal that IFN-λ and type I IFN production were both diminished and delayed, induced only in a fraction of patients as they became critically ill. On the contrary, pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-6 and IL-8 were produced before IFNs in all patients and persisted for a prolonged time. This condition was reflected in blood transcriptomes wherein prominent IFN signatures were only seen in critically ill patients who also exhibited augmented inflammation. By comparison, in 16 patients with influenza (flu) hospitalized for pneumonia with similar clinicopathological characteristics to those of COVID-19 and 24 nonhospitalized patients with flu with milder symptoms, IFN-λ and type I IFN were robustly induced earlier, at higher levels and independently of disease severity, whereas pro-inflammatory cytokines were only acutely produced. Notably, higher IFN-λ concentrations in patients with COVID-19 correlated with lower viral load in bronchial aspirates and faster viral clearance and a higher IFN-λ to type I IFN ratio correlated with improved outcome for critically ill patients. Moreover, altered cytokine patterns in patients with COVID-19 correlated with longer hospitalization and higher incidence of critical disease and mortality compared to flu. These data point to an untuned antiviral response in COVID-19, contributing to persistent viral presence, hyperinflammation and respiratory failure. Andreakos and colleagues provide a longitudinal study comparing patients with COVID-19 to patients infected with influenza. They report a dysregulated interferon response whereby IFN-λ and type I IFN production were diminished and delayed in patients with COVID-19, exhibiting a response that is ‘untuned’ with other inflammatory cytokines.

Asthma is the commonest respiratory disease and one of unceasingly increasing prevalence and burden. As such, asthma has attracted a major share or scientific interest and clinical attention. With the various clinical and pathophysiological aspects of asthma having been extensively investigated, the important association between asthma and physical activity remains underappreciated and insufficiently explored. Asthma impacts adversely on physical activity. Likewise, poor physical activity may lead to worse asthma outcomes. This concise clinical review presents the current recommendations for physical activity, discusses the available evidence on physical activity in asthma, and examines the causes of low physical activity in adult asthmatic patients. It also reviews the effect of daily physical activity and exercise training on the pathology and clinical outcomes of asthma. Finally, it summarizes the evidence on interventions targeting physical activity in asthma.

Air pollution is a significant and widespread issue that presents serious challenges for both human health and the environment because of the presence of a variety of harmful substances in the air, such as tropospheric ozone (O3), particulate matter (PM10), nitrogen oxides (NOx), sulfur dioxide (SO2), and carbon monoxide (CO). In this research, the aim is to evaluate the current evidence for the harmful effects of air pollution on human health, focusing on tropospheric ozone, and to highlight the need for further research in the future. The objective is to evaluate recent data on the respiratory and cardiovascular risks caused by air pollution, the potential association between climate change due to air pollution and human disorders, and the subsequent economic burden. A systematic search of the literature is conducted using PubMed, Scopus, Web of Science, and regulatory reports (EPA), focusing on peer-reviewed studies, epidemiological analyses, and clinical and experimental studies. The key findings indicate that O3 exposure contributes to inflammatory lung injury and to the worsening of preexisting conditions like asthma and COPD, is associated with cancer, and also has numerous negative impacts on neurological, metabolic, and reproductive health, combined with increased healthcare costs. These findings highlight the significance of O3 pollution as a major public health concern, emphasizing the need for immediate measures to decrease emissions and effective policies to protect the climate and the health of the individuals.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide accompanied by a substantial social and economic burden for the patient and the society. Poor sleep quality among COPD patients is frequently unnoticed and unaddressed by physicians and patients themselves, although it is a major source of further deterioration of these patients’ quality of life. The aim of the present study was to record the quality of sleep in COPD patients among the Greek population and correlate these findings with various features of these patients, using the COPD and Asthma Sleep Impact Scale (CASIS). This was a cross-sectional observational study. Forty different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, CASIS questionnaire results, COPD assessment test, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, inhaled COPD treatment report) were collected from 3454 nation-wide COPD patients (Greece). The study sample consisted of COPD patients, mainly male (73%) with a median age of 69 years and a median BMI of 27.2. More than half of COPD patients (60.6%) suffered from moderate disease severity and 23.8% from severe disease, while less than half (42.1%) suffered from at least one exacerbation of the disease over the last year prior study enrollment. About 14% reported frequent to very frequent issues affecting their sleep quality, between a fourth and a third of them reported occasional night sleep disturbances, and at least half of them reported no or very infrequent problems in their night sleep. Our study indicates that the COPD assessment test (CAT) and the spirometry-based disease severity can predict the poorness in the quality of sleep (F 2,3451  = 1397.5, p < 0.001, adj. R2 = 0.45) as assessed by CASIS score, and that the latter also correlates with age (ρ = 0.122, p < 0.001) and disease duration (ρ = 0.104, p < 0.001). On the contrary, there appears to be no correlation between sleep quality and number of exacerbations. Finally, untreated patients with COPD suffer from poorer quality of sleep compared to treated subjects, independently of the use of inhaled corticosteroids (F 2,3451  = 21.65, p < 0.001). The results of the SLEPICO study show that increased age, prolonged disease duration, and especially CAT score ≥ 10, and severe COPD stage, might act as important indicators for deterioration in the quality of sleep, with potential consequences in the daily routine of those patients, thus urging potentially for further pharmacological interventions or modifications.

The increasing availability of data from electronic health records in healthcare organizations and systems has made it feasible to assess the relationship between various environmental parameters (e.g., pollution levels, meteorological data), hospital admissions, morbidity, and mortality associated with lung diseases. This study aimed to assess the correlation between air pollution levels and respiratory function parameters in patients with chronic obstructive lung diseases residing in various regions of the Attica Basin, Greece. Air pollution measurements were obtained from the Department of Atmospheric Quality of the Greek Ministry of Environment and Energy. In particular, data from daily bulletins and air pollution measurements were utilized. Numerical averages were calculated across all monitoring stations. The analysis revealed statistically significant negative correlations between the concentrations of tropospheric ozone (O₃), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and particulate matter (PM₁₀) and the respiratory parameters forced vital capacity (FVC%pred), forced expiratory volume in one second (FEV₁%pred), forced mid-expiratory flow between 25 and 75% of FVC (FEF pred), and peak expiratory flow (PEF%pred) on the day of examination (Day 0). Air pollution measurements were found to be significantly and negatively correlated with lung function parameters. Specifically, increased concentrations of O , CO, SO , NO , and PM  were significantly associated with lower values of the measured lung function parameters. Climate change may significantly affect future levels of O  and the other air pollutants studied in this work. Many regions may face substantial increases in their concentrations, despite the implementation of emission reduction measures. This study clearly highlights the adverse effects of the examined air pollutants on key lung function parameters associated with obstructive lung diseases.

Sestrins (Sesns) are a family of highly conserved stress-inducible proteins and various stresses have been shown to strongly up-regulate them. Sestrin 2 (Sesn2) deficiency has been shown to partially suppress pulmonary emphysema. The aim of this study was to evaluate Sesn2 levels in COPD patients and its possible associations with the presence of emphysema and blood eosinophils. All patients underwent lung function testing and high-resolution computed tomography (HRCT) of the chest. The presence of emphysematous lesions in >15% of the pulmonary parenchyma was considered as significant emphysema. Sixty-seven patients were included in the study. 40/67 patients were characterized as having significant emphysema. Patients with significant emphysema had higher levels of Sesn2 (ng/ml) [median (IQR) 6.7 (2.7,10.3 vs 1.09 (0.9,1.9), p<0.001)] and significantly lower % and absolute blood eosinophil counts (cells/μL) compared to patients without emphysema [1 (0, 2) vs 4 (2, 4) p<0.001 and 62 (0, 110) vs 248 (180, 300), p<0.001 respectively]. Sesn2 presented a significant positive correlation to the score of emphysema in HRCT (r s = 0.87, p<0.001) and similar positive but weaker correlation to FRC (r s = 0.27, p = 0.024). Negative correlations were observed between Sesn2 and either the % of blood eosinophils and/or the absolute blood eosinophil count (r s = -0.79, p<0.001, and r s = -0.78, p<0.001 respectively). Sesn2 levels above 1.87 ng/ml showed a high diagnostic performance for the presence of significant emphysema in HRCT with an AUC 0.93, 95% CI (0.85,0.98), p<0.001. Sesn2 could serve as a potential biomarker of emphysema.

We performed metabolomic profiling to identify metabolites that correlate with disease progression and death. We performed a study of adults hospitalized with Influenza A(H1N1)pdm09. Cases (n = 32) were defined by a composite outcome of death or transfer to the intensive care unit during the 60-day follow-up period. Controls (n = 64) were survivors who did not require transfer to the ICU. Four hundred and eight metabolites from eight families were measured on plasma sample at enrollment using a mass spectrometry based Biocrates platform. Conditional logistic regression was used to summarize the association of the individual metabolites and families with the composite outcome and its major two components. The ten metabolites with the strongest association with disease progression belonged to five different metabolite families with sphingolipids being the most common. The acylcarnitines, glycerides, sphingolipids and biogenic metabolite families had the largest odds ratios based on the composite endpoint. The tryptophan odds ratio for the composite is largely associated with death (OR 17.33: 95% CI, 1.60-187.76). Individuals that develop disease progression when infected with Influenza H1N1 have a metabolite signature that differs from survivors. Low levels of tryptophan had a strong association with death. ClinicalTrials.gov Identifier: NCT01056185.

Advances in the management of malignancies and organ failures have led to substantial increases in survival as well as in the number of cancer patients requiring intensive care unit (ICU) admission. Although effectiveness of ICU in this group remains controversial, the heterogeneity of its population in terms of the nature and curability of their disease and the severity of critical illness and underlying conditions may explain the plethora of issues arising when considering cancer patients for ICU admission, especially from the view of limited resources and ICU beds. The most frequent reasons leading a cancer patient to ICU are postoperative, respiratory failure, infection, and sepsis. Although reasons of admission, nature and number of organ failures, type of malignancy, and therapies that have preceded ICU admission may affect outcome, reliable scoring systems or survival predictors are missing. Literature suggests that organ dysfunction should be managed at its onset, whereas aggressive ICU management should be reappraised after a few days of full support. A multidisciplinary treating team of physicians should aid in changing the goals from restorative to palliative care when there appears to be no possible benefit from any treatment. End-of life-decisions and code status should be made by consensus, based on patients’ autonomy and dignity. Further interventional multicenter studies are required to assess post-ICU burden, long-term medical outcomes, and quality of life in this cohort of patients.

Background Chronic obstructive pulmonary disease (COPD) is a multifactorial clinical condition, characterized by chronic progressive (or worsening) respiratory symptoms, structural pulmonary abnormalities, and impaired lung function, and is often accompanied by multiple, clinically significant comorbid disorders. In 2017, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) issued a new report on COPD prevention, diagnosis and management, aiming at personalizing the maintenance therapeutic approach of the stable disease, based on the patients’ symptoms and history of exacerbations (ABCD assessment approach). Our objective was to evaluate the implementation of GOLD suggestions in everyday clinical practice in Greece. Methods This was a cross-sectional observational study. Sixty-five different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, vaccination data, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, COPD treatments) were collected from 3615 nation-wide COPD patients (Greece). Results The mean age at the time of initial COPD diagnosis was 63.8 (± 10.2). Almost 60% of the subjects were classified into group B, while the remaining patients were falling into groups A (18%) and D (21%), and only a small minority of patients belonged to Group C, according to the ABCD assessment approach. The compliance of respiratory physicians to the GOLD 2017 therapeutic suggestions is problematic, especially when it comes to COPD patients belonging to Group A. Conclusion Our data provide valuable information regarding the demographic and medical profile of COPD patients in Greece, the domains which the revised ABCD assessment approach may show some clinical significance on, and the necessity for medical practitioners dealing with COPD patients to adhere closer to international recommendations for the proper management of the disease.