Comorbid Conditions in a Cohort of Inpatients with SARS-CoV-2 and their Association with In-Hospital Mortality During the Early Phases of the Pandemic.

Introduction: Studies determined that age and associated comorbidities are associated with worse outcomes for COVID-19 patients. The aim of the present study is to examine previous electronic health records of SARS-CoV-2 patients to identify which chronic conditions are associated with in-hospital mortality in a nationally representative sample. Materials and Methods: The actual study is a cross-sectional analysis of SARS-CoV-2 infected patients who were treated in repurposed hospitals. The study includes a cohort of patients treated from 06-11-2020 to 15-03-2021 for COVID-19 associated pneumonia. To examine the presence of comorbidities, electronic health records were examined and analyzed. Results: A total of 1486 in-patients were treated in the specified period, out of which 1237 met the criteria for case. The median age of the sample was 65 years. The overall in-hospital mortality in the sample was 25.5%, while the median length of stay was 11 days. From whole sample, 16.0% of the patients did not have established diagnoses in their electronic records, while the most prevalent coexisting condition was arterial hypertension (62.7%), followed by diabetes mellitus (27.3%). The factors of age, male gender, and the number of diagnoses showed a statistically significant increase in odds ratio (OR) for in-hospital mortality. The presence of chronic kidney injury was associated with the highest increase of OR (by 3.37) for in-hospital mortality in our sample. Conclusion: The study reaffirms the findings that age, male gender, and the presence of comorbidities are associated with in-hospital mortality in COVID-19 treated and unvaccinated patients. Our study suggests that chronic kidney injury showed strongest association with the outcome, when adjusted for age, gender, and coexisting comorbidities.

Management of anaphylaxis due to COVID-19 vaccines in the elderly.

Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID-19 vaccines due to high risk of death. In very rare instances, the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.

Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA2 LEN consensus.

BACKGROUND: Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. METHODS: A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. RESULTS: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). CONCLUSIONS: This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.

Pitolisant for Residual Excessive Daytime Sleepiness in OSA Patients Adhering to CPAP: A Randomized Trial.

BACKGROUND: Excessive daytime sleepiness (EDS) in individuals with OSA syndrome persisting despite good adherence to CPAP is a disabling condition. Pitolisant is a selective histamine H3-receptor antagonist with wake-promoting effects. RESEARCH QUESTION: Is pitolisant effective and safe for reducing daytime sleepiness in individuals with moderate to severe OSA adhering to CPAP treatment but experiencing residual EDS? STUDY DESIGN AND METHODS: In a multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was titrated individually at up to 20 mg/day and taken over 12 weeks. The primary end point was change in the Epworth Sleepiness Scale (ESS) score in the intention-to-treat population. Key secondary end points were maintenance of wakefulness assessed by the Oxford Sleep Resistance Test, Clinical Global Impressions scale of severity, the patient's global opinion, EuroQoL quality-of-life questionnaire score, Pichot fatigue questionnaire score, and safety. RESULTS: Two hundred forty-four OSA participants (82.8% men; mean age, 53.1 years; mean Apnea Hypopnea Index with CPAP, 4.2/h; baseline ESS score, 14.7) were randomized to pitolisant (n = 183) or placebo (n = 61). ESS significantly decreased with pitolisant compared with placebo (-2.6; 95% CI, -3.9 to -1.4; P < .001), and the rate of responders to therapy (ESS ≤ 10 or change in ESS ≥ 3) was significantly higher with pitolisant (71.0% vs 54.1%; P = .013). Adverse event occurrence (mainly headache and insomnia) was higher in the pitolisant group compared with the placebo group (47.0% and 32.8%, respectively; P = .03). No cardiovascular or other significant safety concerns were reported. INTERPRETATION: Pitolisant used as adjunct to CPAP therapy for OSA with residual sleepiness despite good CPAP adherence significantly reduced subjective and objective sleepiness and improved participant-reported outcomes and physician-reported disease severity. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01071876; URL: www.clinicaltrials.gov; EudraCT N°: 2009-017248-14; URL: eudract.ema.europa.eu.

Obstructive Sleep Apnea and Lipid Abnormalities.

BACKGROUND: There has been a great interest in the interaction between obstructive sleep apnea (OSA) and metabolic dysfunction, but there is no consistent data suggesting that OSA is a risk factor for dyslipidemia. AIM: The aim of this cross-sectional study was to evaluate the prevalence of lipid abnormalities in patients suspected of OSA, referred to our sleep laboratory for polysomnography. MATERIAL AND METHODS: Two hundred patients referred to our hospital with suspected OSA, and all of them underwent for standard polysomnography. All patients with respiratory disturbance index (RDI) above 15 were diagnosed with OSA. In the morning after 12 hours fasting, the blood sample was collected from all patients. Blood levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL), were determined in all study patients. In the study, both OSA positive and OSA negative patients were divided according to the body mass index (BMI) in two groups. The first group with BMI ≤ 30 kg/m^2 and the second group with BMI > 30 kg/m^2. RESULTS: OSA positive patients with BMI ≤ 30 kg/m^2 had statistically significant higher levels of triglycerides and total cholesterol, and statistically significant lower level of HDL compared to OSA negative patients with BMI ≤ 30. There were no statistically significant differences in age and LDL levels between these groups. OSA positive patients with BMI > 30 kg/m^2 had higher levels of triglycerides, total cholesterol and LDL and lower levels of HDL versus OSA negative patients with BMI > 30 kg/m^2, but without statistically significant differences. CONCLUSION: OSA and obesity are potent risk factors for dyslipidemias. OSA could play a significant role in worsening of lipid metabolism in non-obese patients. But in obese patients, the extra weight makes the metabolic changes of lipid metabolism, and the role of OSA is not that very important like in non-obese patients.

Relationship between Vitamin D, Inflammation and Lung Function In Patients with Severe Uncontrolled Asthma.

BACKGROUND: Recently epidemiological studies showed that low vitamin D is linked to airway hyperresponsiveness, decreased lung function, poor asthma control, and steroid-resistant asthma. AIM: We investigated the relationship between Vitamin D, inflammation with circulating IL-33 and lung function in 30 patients with severe uncontrolled asthma. MATERIALS AND METHODS: The study included 30 patients with severe uncontrolled asthma. In each of them were measured serum levels of IL-33 and Vitamin D by the ELISA method. The pulmonary function is measured by basic spirometry parameters, FEV1. The results were statistically elaborated according to the Pearson's Correlation Tests. RESULTS: The results showed statistically insignificant correlation between Vitamin D and IL-33, and Vitamin D with FEV1 (Vit.D/IL-33; r = 0.11323, p = 0.551); (Vit.D/FEV1; r = -0.1005; p = 0.597) Correlation between IL-33 and FEV1 is negative but statistically significant (IL-33/FEV1; r = -0.5248; p = 0.003). CONCLUSION: Because there are little studies about the link between vitamin D and asthma, further research to clarify the mechanism how vitamin D control the activity of CD4+ T cells and the related Th2-type cytokines in the parthenogenesis of asthma.

Azithromycin in treatment of patients with asthma and C. Pneumoniae infection.

Chronic C. pneumoniae infection has been suggested as a cause for adult onset of asthma. There are data to suggest that infectious organisms, particularly the atypical bacteria C. pneumoniae, may be involved in asthma pathogenesis. The significance of these organisms is as yet unclear. It is not known whether this organism was allowed to persist after an infection, or was present prior to the development of asthma. The purpose of this study was to determine whether anti-chlamydial treatment with azithromycin will improve asthma symptoms and lung function in asthmatic patients positive for C. pneumoniae. For this purpose, 20 patients (mean age 39.8 years) with mild asthma were treated a median of 8 weeks with azithromycin 1000 mg once weekly. All patients had C. pneumoniae infection detected by Seeplex Multiplex PCR in sputum and positive IgG titre>1:64 and IgA titre>1:16 antibodies against C. pneumoniae. Post treatment lung function, symptom score (cough, wheezing, dyspnea), morning and evening PEF values and ß2-agonist use were compared with baseline values. After 8 weeks of treatment with azithromycin there was a significant reduction in symptom score (p<0.001) and a significant improvement in lung function FEV1 (p<0.001), morning and evening PEF values p<0.05 Wilcoxon matched Pairs test. We also found a reduction in ß2-agonist use, but it was not statistically significant. Treatment with azithromycin significantly improved asthma symptoms and lung function, indicating that C. pneumoniae may play an important role in enhancing the inflammatory processes in the lower airways.

Efficacy and safety of moxifloxacin in acute exacerbations of chronic bronchitis: a prospective, multicenter, observational study (AVANTI).

BACKGROUND: Acute exacerbations of chronic bronchitis (AECB), including chronic obstructive pulmonary disease (AECOPD), represent a substantial patient burden. Few data exist on outpatient antibiotic management for AECB/AECOPD in Eastern/South Eastern Europe, in particular on the use of moxifloxacin (Avelox®), although moxifloxacin is widely approved in this region based on evidence from international clinical studies. METHODS: AVANTI (AVelox® in Acute Exacerbations of chroNic bronchiTIs) was a prospective, observational study conducted in eight Eastern European countries in patients > 35 years with AECB/AECOPD to whom moxifloxacin was prescribed. In addition to safety and efficacy outcomes, data on risk factors and the impact of exacerbation on daily life were collected. RESULTS: In the efficacy population (N = 2536), chronic bronchitis had been prevalent for > 10 years in 31.4% of patients and 66.0% of patients had concomitant COPD. Almost half the patients had never smoked, in contrast to data from Western Europe and the USA, where only one-quarter of COPD patients are non-smokers. The mean number of exacerbations in the last 12 months was 2.7 and 26.3% of patients had been hospitalized at least once for exacerbation. Physician compliance with the recommended moxifloxacin dose (400 mg once daily) was 99.6%. The mean duration of moxifloxacin therapy for the current exacerbation (Anthonisen type I or II in 83.1%; predominantly type I) was 6.4 ± 1.9 days. Symptom improvement was reported after a mean of 3.4 ± 1.4 days. After 5 days, 93.2% of patients reported improvement and, in total, 93.5% of patients were symptom-free after 10 days. In the safety population (N = 2672), 57 (2.3%) patients had treatment-emergent adverse events (TEAEs) and 4 (0.15%) had serious TEAEs; no deaths occurred. These results are in line with the known safety profile of moxifloxacin. CONCLUSIONS: A significant number of patients in this observational study had risk factors for poor outcome, justifying use of moxifloxacin. The safety profile of moxifloxacin and its value as an antibiotic treatment were confirmed. Physicians complied with the recommended 400 mg once-daily dose in a large proportion of patients, confirming the advantages of this simple dosing regimen. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00846911.

Induction of the epidermal growth factor receptor and its ligands in nasal epithelium by ozone.

BACKGROUND: Ozone is a photochemical oxidant pollutant that is an important public health hazard. Although the inflammatory response that occurs in response to ozone inhalation is well characterized, the mechanisms underlying epithelial cell activation are not well understood. OBJECTIVE: Because the epidermal growth factor receptor (EGFR) is a central regulator of epithelial function, we tested the hypothesis that nasal epithelial cells respond to ozone-induced oxidant stress by modulating expression of the EGFR and its ligands, EGF and transforming growth factor-alpha (TGF-alpha). METHODS: Normal volunteers were exposed to air or 400 parts per billion ozone for 2 hours, and then nasal biopsy specimens were harvested 6 hours later for immunohistochemical analysis of EGFR, EGF, and TGF-alpha. Nasal epithelial cell cultures were exposed in vitro to ozone or TNF-alpha; mediator release was measured by ELISA and cellular EGFR expression by immunoblotting and fluorescence-activated cell sorting analysis. RESULTS: Epithelial expression of the EGFR, EGF, and TGF-alpha were all significantly (P <.05) increased in the nasal biopsy specimens after ozone exposure, and there was a significant positive correlation between EGFR expression and the increase in neutrophil numbers in the nasal epithelium (P =.001, rho = 0.87). In vitro exposure of primary nasal epithelial cell cultures to ozone had no effect on EGFR expression, even though IL-8 release was enhanced. In contrast, exposure to TNF-alpha caused EGFR levels to increase significantly. CONCLUSION: These data suggest that the ozone-induced increase in EGFR expression observed in vivo is indirect, perhaps mediated by neutrophil-derived TNF-alpha.