A central paradigm of immunity is that interferon (IFN)-mediated antiviral responses precede pro-inflammatory ones, optimizing host protection and minimizing collateral damage
. 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.
Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD. Recent data provide evidence for a role in the NLRP3 ...inflammasome in the airway inflammation observed in COPD. Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs) to release “danger signal”. These signals act as ligands to Toll-like receptors (TLRs), triggering the production of cytokines and inducing innate inflammation. In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells. Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs). Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD. This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD.
Abstract Objectives The goal of this study was to assess the independent and collective diagnostic value of various modalities in cardiac sarcoidosis, delineate the role of cardiac magnetic resonance ...(CMR), and identify patients at risk. Background Cardiac sarcoidosis is associated with increased morbidity and mortality. CMR is a key modality in the evaluation of patients with cardiac symptoms, but the complementary role of CMR to conventional tests for the diagnosis of cardiac sarcoidosis is not fully defined. Methods Patients (N = 321) with biopsy-proven sarcoidosis underwent conventional cardiac testing and CMR with late gadolinium enhancement (LGE) and were followed up for primary (composite of all-cause mortality, sustained ventricular tachycardia VT episodes, or hospitalization for heart failure) and secondary (nonsustained VT episodes) endpoints. Results Cardiac sarcoidosis was diagnosed in 29.9% of patients according to the Heart Rhythm Society consensus criteria. CMR was the most sensitive and specific test (area under the curve: 0.984); it detected 44 patients with cardiac symptoms and/or electrocardiogram (ECG) abnormalities but normal echocardiogram, as well as 15 asymptomatic patients with normal baseline testing. Echocardiography added to cardiac history and ECG did not change sensitivity of the initial screening strategy (68.8% vs. 72.9%). Despite a high positive predictive value (83.9%), echocardiography had a low sensitivity (27.1%). During follow-up, 7.2% of patients reached the primary endpoint and another 3.4% reached the secondary endpoint. LGE was and independent predictor of primary endpoints (hazard ratio: 5.68; 95% CI: 1.74 to 18.49; p = 0.004). LGE, age, and baseline nonsustained VT were independent predictors of all events. In patients with cardiac symptoms and/or an abnormal ECG, CMR increased diagnostic accuracy and independently predicted primary endpoints (hazard ratio: 12.71; 95% confidence interval: 1.48 to 109.35; p = 0.021). Conclusions Of all cardiac tests, CMR was the most valuable in the diagnosis and prognosis of cardiac sarcoidosis in a general sarcoidosis population. Echocardiography had an overall limited diagnostic value as a screening test, and an abnormal study, despite a high positive predictive value, may still need confirmation with CMR.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder with a course that is not uniform for all COPD patients. Although smoking is considered as the major cause of the ...disease, persistent or recurrent infections seem to play a particular role in the disease establishment and progression. COPD is characterized by dysregulated immunity that has been associated with the bacterial colonization and infections.
The establishment of culture-independent techniques has shed new light on the relationships between bacterial ecology and health status and expanded our knowledge on the lung microbiome. Interactions between the host and lung microbiome result in inflammation and activation of resident cells. The lung microbiome contains populations of symbionts and pathobionts in balance which lose their equilibrium and disturb the balance of T-helper and regulatory T-cells (Treg) upon infection, or lung disease. In COPD factors such as disease severity, exacerbations, degree of inflammation, and type of treatment used (e.g inhaled or systemic steroids and antibiotics) affect the composition of lung microbiota. Recent data indicate that the presence of specific bacterial taxa in the airways has the potential to influence the host immune response and possibly to interfere with disease phenotype. Although, there is a growing body of evidence for the role of microbiome in COPD several unanswered questions still exist for its clinical relevance.
•The lung microbiome in chronic obstructive pulmonary disease (COPD) has a dynamic nature between stable state and exacerbation.•Specific bacterial taxa in the airways may influence the host immune response and shape disease phenotypes and endotypes.•However, the mechanisms by which microbiota regulate disease development and progression are not clear, as yet.•The better understanding of these mechanisms could enable the development of novel treatments to improve the clinical outcomes in these patients
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.
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
= 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
= 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.
Abstract 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.
Highlights • Serological, molecular and phylogenetic analysis of a recently imported case of MERS coronavirus (MERS-CoV) in Greece. • MERS-CoV remained detectable in the respiratory tract secretions ...of the patient until the fourth week of illness, whereas viraemia was last detected two days after the institution of the triple combination therapy. • The non-detectable viral RNA in serum by day 3 after the initiation of the antiviral treatment could be explained either by viral clearance in an otherwise immunocompetent person or by effectiveness of the instituted antiviral regimen.
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