Chronic obstructive pulmonary disease (COPD) is the fifth cause of morbidity and mortality in the developed world and represents a substantial economic and social burden. Patients experience a progressive deterioration up to end-stage COPD, characterised by very severe airflow limitation, severely limited and declining performance status with chronic respiratory failure, advanced age, multiple comorbidities and severe systemic manifestations/ complications.COPD is frequently underdiagnosed and under-treated. Today, COPD develops earlier in life and is less gender specific. Tobacco smoking is the major risk factor for COPD, followed by occupation and air pollution. Severe deficiency for a 1 -antitrypsin is rare; several phenotypes are being associated with elevated risk for COPD in the presence of risk factor exposure. Any patient presenting with cough, sputum production or dyspnoea should be assessed by standardised spirometry. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk for repeated exacerbations, eventually leading to end-stage disease.Without major efforts in prevention, there will be an increasing proportion of end-stage patients who can live longer through long-term oxygen therapy and assisted ventilation, but with elevated suffering and huge costs. Smoking prevention and smoking cessation are the most important epidemiological measurements to counteract chronic obstructive pulmonary disease epidemics.

Results, NCT02777996.

Smoking cessation is the one of the most important ways to improve the prognosis of patients with respiratory disease. The Task Force on guidelines for smoking cessation in patients with respiratory diseases was convened to provide evidence-based recommendations on smoking cessation interventions in respiratory patients.Based on the currently available evidence and the consensus of an expert panel, the following key recommendations were made. 1) Patients with respiratory disease have a greater and more urgent need to stop smoking than the average smoker, so respiratory physicians must take a proactive and continuing role with all smokers in motivating them to stop and in providing treatment to aid smoking cessation. 2) Smoking cessation treatment should be integrated into the management of the patient's respiratory condition. 3) Therapies should include pharmacological treatment (i.e. nicotine replacement therapy, bupropion or varenicline) combined with behavioural support. 4) Respiratory physicians should receive training to ensure that they have the knowledge, attitudes and skills necessary to deliver these interventions or to refer to an appropriate specialist. 5) Although the cost of implementing these recommendations will partly be offset by a reduction in attendance for exacerbations, etc., a budget should be established to enable implementation.Research is needed to establish optimum treatment strategies specifically for respiratory patients.

Using AI we identified baricitinib as possessing anti-viral and anti-cytokine efficacy. We now show a 71% (95% CI 0.15-0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age 81 years). A further 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-alpha-2 (IFNα2) significantly increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by >5-fold. RNA-Seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and super-resolution microscopy, baricitinib exerts activity rapidly through the inhibition of host proteins (numb associated kinases), uniquely amongst anti-virals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication and the cytokine storm, and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivizes further randomized controlled trials.

Background Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19. Objectives To identify predictors of superinfections in COVID-19. Methods Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred ≥48 h after hospital admission. A multivariate analysis was performed to identify factors independently associated with superinfections. Results Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11–29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfections were: intestinal colonization by carbapenem-resistant Enterobacterales (OR 16.03, 95% CI 6.5–39.5, P < 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4–13.1, P < 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2–11.8, P < 0.001); C-reactive protein on admission >7 mg/dl (OR 3.59, 95% CI 1.7–7.7, P = 0.001); and previous treatment with piperacillin/tazobactam (OR 2.85, 95% CI 1.1–7.2, P = 0.028). Length of hospital stay was longer in patients who developed superinfections ompared with those who did not (30 versus 11 days, P < 0.001), while mortality rates were similar (18.8% versus 23.2%, P = 0.445). Conclusions The risk of bacterial and fungal superinfections in COVID-19 is consistent. Patients who need empiric broad-spectrum antibiotics and immunomodulant drugs should be carefully selected. Infection control rules must be reinforced.

Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of morbidity and mortality in the industrialized and the developing countries. During 1997, COPD has been estimated to be the number four cause of death after cardiovascular diseases, tumors and cerebrovascular diseases in the United States. In 2020 COPD will probably become the third leading cause of death all over the world, following the trend of increasing prevalence of lung cancer. The impact of this respiratory disease worldwide is expected to increase with a heavy economic burden on individuals and society. In the United States direct and indirect costs of COPD were estimated at about USD24 billion in 1993. Unfortunately, there are few data on health-care utilization despite the great interest in COPD among researchers. As all chronic diseases, the prevalence of COPD is strongly associated with age. Data collected in a general population sample (living in Italy) showed a progressive increase of the prevalence of chronic bronchitis and emphysema with age, both in males and in females. COPD is determined by the action of a number of various risk factors either singly or interacting among themselves in a synergistic way. Among these, the most important is cigarette smoking, ranking at the first level for developing chronic bronchitis and emphysema. Also air pollution and some occupational exposures represent risks for developing COPD. Many epidemiological studies have indicated an association between the prevalence of chronic bronchitis and a low socioeconomic status. Furthermore, in the etiology of COPD we must consider endogenous risk factors such as gender, genetic features, presence of respiratory troubles in childhood, and family history. To date, epidemiologic studies have been of great importance for the characterization of the disease at a population level, indicating possible causes and assessing its impact on the individual and on society as a whole. Unfortunately, international standards for the diagnosis of COPD are lacking, which complicates the organization of appropriate epidemiological surveys.

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Background and aims There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m 2 ; HR = 2.3; 1.5–3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. Conclusions Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.