Glucocorticosteroids (GCS) are used on a daily basis to reduce airway inflammation in asthma and chronic obstructive pulmonary disease (COPD). This treatment is usually escalated during acute disease exacerbations, events often associated with virus infections.
We examined the impact of GCS on anti-viral defences and virus replication and assessed supplementary interferon (IFN) treatment. Here, we report that treatment of primary human airway cells in vitro with GCS prior to rhinovirus (RV) or influenza A virus (IAV) infection significantly reduces the expression of innate anti-viral genes and increases viral replication. Mice given intranasal treatment with GCS prior to IAV infection developed more severe disease associated with amplified virus replication and elevated inflammation in the airways. Adjuvant IFN treatment markedly reduced GCS-amplified infections in human airway cells and in mouse lung.
This study demonstrates that GCS cause an extrinsic compromise in anti-viral defences, enhancing respiratory virus infections and provides a rationale for adjuvant IFN treatment.
BACKGROUND AND OBJECTIVE: Bronchoscopic lung volume reduction coil (LVR-coil) treatment has been shown to be safe and clinically effective in patients with severe emphysema in the short term; however, long-term safety and effectiveness has not been evaluated. The aim of this study was to investigate the long-term safety and effectiveness of LVR-coil treatment in patients with severe emphysema.
METHODS: Thirty-eight patients with severe emphysema (median age is 59 years, forced expiratory volume in 1 s is 27% predicted) who were treated in LVR-coil clinical trials were invited for a voluntary annual visit. Safety was evaluated by chest X-ray and recording of adverse events and by efficacy by pulmonary function testing, 6-min walk distance (6MWD) and questionnaires.
RESULTS: Thirty-five patients visited the hospital 1 year, 27 patients 2 years and 22 patients 3 years following coil placement. No coil migrations were observed on X-rays. At 1-year follow-up, all clinical outcomes significantly improved compared with baseline. At 2 years, residual volume % pred, modified Medical Research Council (mMRC) and the SGRQ score were still significantly improved. At 3 years, a significant improvement in mMRC score remained, with 40% of the patients reaching the 6MWD minimal important difference, and 59% for the St George's Respiratory Questionnaire (SGRQ) minimal important difference.
CONCLUSIONS: Follow-up of the patients treated with LVR-coils in our pilot studies showed that the coil treatment is safe with no late pneumothoraces, coil migrations or unexpected adverse events. Clinical benefit gradually declines over time; at 3 years post-treatment, around 50% of the patients maintained improvement in 6MWD, SGRQ and mMRC.
CLINICAL TRIAL REGISTRATION: NCT01220908 and NCT01328899 registered at ClinicalTrials.gov.
Continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV) are frequently used inhospital for treating respiratory failure, especially in treatment of acute cardiogenic pulmonary edema and exacerbation of chronic obstructive pulmonary disease. Early initiation of treatment is important for success and introduction already in the prehospital setting may be beneficial.
Our goal was to assess the evidence for an effect of prehospital CPAP or NIV as a supplement to standard medical treatment alone on the following outcome measures; mortality, hospital length of stay, intensive care unit length of stay, and intubation rate.
We undertook a systematic review based on a search in the three databases: PubMed, EMBASE, and Cochrane. We included 12 studies in our review, but only four of these were of acceptable size and quality to conclude on our endpoints of interest. All four studies examine prehospital CPAP. Of these, only one small, randomized controlled trial shows a reduced mortality rate and a reduced intubation rate with supplemental CPAP. The other three studies have neutral findings, but in two of these a trend toward lower intubation rate is found. The effect of supplemental NIV has only been evaluated in smaller studies with insufficient power to conclude on our endpoints. None of these studies have shown an effect on neither mortality nor intubation rate, but two small, randomized controlled trials show a reduction in intensive care unit length of stay and a trend toward lower intubation rate. The risk of both type two errors and publication bias is evident, and the findings are not consistent enough to make solid conclusion on supplemental prehospital NIV.
Large, randomized controlled trials regarding the effect of NIV and CPAP as supplement to standard medical treatment alone, in the prehospital setting, are needed.