Use of Inhaled Corticosteroids and Risk of Acquiring Haemophilus influenzae in Patients with Chronic Obstructive Pulmonary Disease.

Background: Inhaled corticosteroids (ICS) are widely used in chronic obstructive pulmonary disease (COPD), despite the known risk of severe adverse effects including pulmonary infections. Research Question: Our study investigates the risk of acquiring a positive Haemophilus influenzae airway culture with use of ICS in outpatients with COPD. Study Design and Methods: We conducted an epidemiological cohort study using data from 1 January 2010 to 19 February 2018, including 21,218 outpatients with COPD in Denmark. ICS use 365 days prior to cohort entry was categorised into low, moderate, and high, based on cumulated ICS dose extracted from a national registry on reimbursed prescriptions. A Cox proportional hazards regression model was used to assess the future risk of acquiring H. Influenzae within 365 days from cohort entry, and sensitivity analyses were performed using propensity score matched models. Results: In total, 801 (3.8%) patients acquired H. Influenzae during follow-up. Use of ICS was associated with a dose-dependent increased risk of acquiring H. Influenzae with hazard ratio (HR) 1.2 (95% confidence interval (CI) 0.9−1.5, p value = 0.1) for low-dose ICS; HR 1.7 (95% CI 1.3−2.1, p value < 0.0001) for moderate dose; and HR 1.9 (95% CI 1.5−2.4, p value < 0.0001) for high-dose ICS compared to no ICS use. Results were confirmed in the propensity-matched model using the same categories. Conclusions: ICS use in outpatients with COPD was associated with a dose-dependent increase in risk of isolating H. Influenzae. This observation supports that high dose ICS should be used with caution.

Status: nosocomial transmission and prevention of SARS-CoV-2 in a Danish context.

The unexpected pandemic with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged the healthcare sector as regards preventing and controlling the virus from spreading between patients and hospital personnel. The massive spread of the pandemic has led state authorities to introduce restrictions on society and public behavior unprecedented in modern times. First, we describe the Danish effort regarding standard precautions, personal protective equipment, and disinfection in the healthcare setting with Denmark as an example. As regards, the number of coronavirus disease 2019 (COVID-19)-related hospital submissions, deaths, and infected healthcare workers in Denmark is not the hardest hit country compared with others. This cannot be explained by the hardness of the restrictions alone. Several aspects concerning the person-to-person spread of SARS-CoV-2 are not fully understood and require more experimental studies. The dogma is that virus transmission happens through either respiratory droplets or contact routes. However, it is likely not the whole truth, as we describe scenarios where droplets and/or direct contact cannot alone explain how all patients were infected. Aspects of the physiology of airborne transmission are considered, as several parameters are in play beyond particle size and respiratory rate. These are ozone concentration, ambient temperature, and humidity. In a hospital environment, these factors are not necessarily all controllable, making infection prevention and control a challenge.

Early IL-2 treatment of mice with Pseudomonas aeruginosa pneumonia induced PMN-dominating response and reduced lung pathology.

IL-2 is a pro-inflammatory and a Th1 inducing cytokine, which is important for activation of the cell-mediated immunity. IL-2 in serum and sputum has been observed to be reduced in cystic fibrosis (CF) patients. The present IL-2 treatment study of Pseudomonas aeruginosa (PA) lung infected mice was performed in order to evaluate the effect of IL-2 supplement. One hundred-and-twenty female BALB/c mice were divided into three groups: 1) IL-2 treatment/infection (TIG), 2) non-treatment/infection (NTIG), and 3) IL-2 treatment/non-infection (TNIG). The mice were challenged intra-tracheally with PA (PAO579) embedded in seaweed alginate to resemble the biofilm mode of growth. At day 0 and 1, the treatment groups received IL-2 s.c. Mice were killed on day 1 or 2, and cytokine production, lung pathology, and quantitative lung bacteriology were estimated. IL-2 treatment of infected mice reduced the number of mice with signs of macroscopic lung pathology at day 2 (p < 0.05). The reduced macroscopic pathology was paralleled by a reduced IL-1ß and TNF-α. In contrast, an increased PMN response at day 2 was observed in the IL-2 treated mice (p < 0.01). This was preceded by a significantly higher degree of microscopic inflammation at day 1 (p < 0.02). The IL-12 levels decreased in both groups of infected mice at day 2 (p < 0.01), however, significantly more in the IL-2 treated mice (p < 0.02). In accordance, but surprisingly, IFN-γ was significantly reduced in the IL-2 treated PA infected group at day 2 (p < 0.05). The present results indicate that early IL-2 treatment prolongs the PMN response but also reduces pro-inflammatory IL-1ß and TNF-α and macroscopic signs of pathology.