Clinical factors associated with smoking cessation among smokers with Chronic Obstructive Pulmonary Disease by sex: Longitudinal analyses from French smoking cessation services.

Background: Smoking is responsible for 80 % of cases of Chronic Obstructive Pulmonary Disease (COPD), while the prognosis is improved by smoking cessation (SC). We examined clinical factors associated with SC among smokers with COPD comparing women and men. Methods: The study comprised a cohort of 1470 smokers who visited a SC service and completed at least 28-day of follow-up visits. The outcome was smoking status at follow-up (abstinence, reduction, no change). Abstinence was defined as continuous abstinence for at least 28 days, validated by the measurement of expired Carbon Monoxide. Reduction was defined as a halving of the baseline tobacco consumption. Results: The average age of the population was 53 (±11) years and 58.2 % were women. Men were 2 years younger than women and consulted more likely after a hospital contact, whereas women consulted on their own initiative. Women more often had a depression history, whereas men had medical comorbidities and co-addictions. There was no significant difference by sex regarding the abstinence rate (41.0 % in women vs 40.7 in men, p > 0.9). The factors significantly associated with higher abstinence rates in both sexes were: at least one previous quit attempt and number of follow-up visits ≥4. The factors negatively associated with quitting in women were diabetes, intake of mood stabilizers and consuming more than 10 cigarettes per day while having a chronic bronchitis, taking antidepressants and having consumed cannabis in the last 30 days hampered SC in men. Conclusions: Concerning factors associated with SC, few differences were found between female and male smokers suffering from COPD. However, due to the different medical and smoking behavior characteristics according to sex, it might be important to take these differences into account in order to provide tailored SC management.

Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients

BackgroundCoronavirus disease 2019 (Covid-19) is a major global threat that has already caused more than 100,000 deaths worldwide. It is characterized by distinct patterns of disease progression implying a diverse host immune response. However, the immunological features and molecular mechanisms involved in Covid-19 severity remain so far poorly known. MethodsWe performed an integrated immune analysis that included in-depth phenotypical profiling of immune cells, whole-blood transcriptomic and cytokine quantification on a cohort of fifty Covid19 patients with a spectrum of disease severity. All patient were tested 8 to 12 days following first symptoms and in absence of anti-inflammatory therapy. ResultsA unique phenotype in severe and critically ill patients was identified. It consists in a profoundly impaired interferon (IFN) type I response characterized by a low interferon production and activity, with consequent downregulation of interferon-stimulated genes. This was associated with a persistent blood virus load and an exacerbated inflammatory response that was partially driven by the transcriptional factor NFB. It was also characterized by increased tumor necrosis factor (TNF)- and interleukin (IL)-6 production and signaling as well as increased innate immune chemokines. ConclusionWe propose that type-I IFN deficiency in the blood is a hallmark of severe Covid-19 and could identify and define a high-risk population. Our study provides a rationale for testing IFN administration combined with adapted anti-inflammatory therapy targeting IL-6 or TNF- in most severe patients. These data also raise concern for utilization of drugs that interfere with the IFN pathway.

No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial

BackgroundTreatments are urgently needed to prevent respiratory failure and deaths from coronavirus disease 2019 (COVID-19). Hydroxychloroquine (HCQ) has received worldwide attention because of positive results from small studies. MethodsWe used data collected from routine care of all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen [≥] 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day. The composite primary endpoint was transfer to intensive care unit (ICU) within 7 days from inclusion and/or death from any cause. Analyses were adjusted for confounding factors by inverse probability of treatment weighting. ResultsThis study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group). Initial severity was well balanced between the groups. In the weighted analysis, 20.2% patients in the HCQ group were transferred to the ICU or died within 7 days vs 22.1% in the no-HCQ group (16 vs 21 events, relative risk [RR] 0.91, 95% CI 0.47-1.80). In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no-HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13-2.89), and 27.4% and 24.1%, respectively, developed acute respiratory distress syndrome within 7 days (24 vs 23 events, RR 1.14, 95% CI 0.65-2.00). Eight patients receiving HCQ (9.5%) experienced electrocardiogram modifications requiring HCQ discontinuation. InterpretationThese results do not support the use of HCQ in patients hospitalised for documented SARS-CoV-2-positive hypoxic pneumonia.

Asthma-Related Outcomes in Patients Initiating Extrafine Ciclesonide or Fine-Particle Inhaled Corticosteroids

PURPOSE: Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone). METHODS: This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as ciclesonide or fine-particle ICS. The 2 cohorts were matched 1:1 for key demographic and clinical characteristics over the baseline year. Co-primary endpoints were 1-year severe exacerbation rates, risk-domain asthma control, and overall asthma control; secondary endpoints included therapy change. RESULTS: Each cohort included 1,244 patients (median age 45 years; 65% women). Patients in the ciclesonide cohort were comparable to those in the fine-particle ICS cohort apart from higher baseline prevalence of hospitalization, gastroesophageal reflux disease, and rhinitis. Median (interquartile range) prescribed doses of ciclesonide and fine-particle ICS were 160 (160-160) µg/day and 500 (250-500) µg/day, respectively (P<0.001). During the outcome year, patients prescribed ciclesonide experienced lower severe exacerbation rates (adjusted rate ratio [95% CI], 0.69 [0.53-0.89]), and higher odds of risk-domain asthma control (adjusted odds ratio [95% CI], 1.62 [1.27-2.06]) and of overall asthma control (2.08 [1.68-2.57]) than those prescribed fine-particle ICS. The odds of therapy change were 0.70 (0.59-0.83) with ciclesonide. CONCLUSIONS: In this matched cohort analysis, we observed that initiation of ICS with ciclesonide was associated with better 1-year asthma outcomes and fewer changes to therapy, despite data suggesting more difficult-to-control asthma. The median prescribed dose of ciclesonide was one-third that of fine-particle ICS.