Determinants of Anti-S Immune Response at 12 Months after SARS-CoV-2 Vaccination in a Multicentric European Cohort of Healthcare Workers-ORCHESTRA Project.

BACKGROUND: The effectiveness of the immunity provided by SARS-CoV-2 vaccines is an important public health issue. We analyzed the determinants of 12-month serology in a multicenter European cohort of vaccinated healthcare workers (HCW). METHODS: We analyzed the sociodemographic characteristics and levels of anti-SARS-CoV-2 spike antibodies (IgG) in a cohort of 16,101 vaccinated HCW from eleven centers in Germany, Italy, Romania, Slovakia and Spain. Considering the skewness of the distribution, the serological levels were transformed using log or cubic standardization and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log or cubic antibody level and the corresponding 95% confidence interval (CI) for different factors and combined them in random-effects meta-analyses. RESULTS: We included 16,101 HCW in the analysis. A high antibody level was positively associated with age (RR = 1.04, 95% CI = 1.00-1.08 per 10-year increase), previous infection (RR = 1.78, 95% CI 1.29-2.45) and use of Spikevax [Moderna] with combinations compared to Comirnaty [BioNTech/Pfizer] (RR = 1.07, 95% CI 0.97-1.19) and was negatively associated with the time since last vaccine (RR = 0.94, 95% CI 0.91-0.98 per 30-day increase). CONCLUSIONS: These results provide insight about vaccine-induced immunity to SARS-CoV-2, an analysis of its determinants and quantification of the antibody decay trend with time since vaccination.

Multimorbidity and Serological Response to SARS-CoV-2 Nine Months after 1st Vaccine Dose: European Cohort of Healthcare Workers-Orchestra Project.

Understanding antibody persistence concerning multimorbidity is crucial for vaccination policies. Our goal is to assess the link between multimorbidity and serological response to SARS-CoV-2 nine months post-first vaccine. We analyzed Healthcare Workers (HCWs) from three cohorts from Italy, and one each from Germany, Romania, Slovakia, and Spain. Seven groups of chronic diseases were analyzed. We included 2941 HCWs (78.5% female, 73.4% ≥ 40 years old). Multimorbidity was present in 6.9% of HCWs. The prevalence of each chronic condition ranged between 1.9% (cancer) to 10.3% (allergies). Two regression models were fitted, one considering the chronic conditions groups and the other considering whether HCWs had diseases from ≥2 groups. Multimorbidity was present in 6.9% of HCWs, and higher 9-months post-vaccine anti-S levels were significantly associated with having received three doses of the vaccine (RR = 2.45, CI = 1.92-3.13) and with having a prior COVID-19 infection (RR = 2.30, CI = 2.15-2.46). Conversely, lower levels were associated with higher age (RR = 0.94, CI = 0.91-0.96), more time since the last vaccine dose (RR = 0.95, CI = 0.94-0.96), and multimorbidity (RR = 0.89, CI = 0.80-1.00). Hypertension is significantly associated with lower anti-S levels (RR = 0.87, CI = 0.80-0.95). The serological response to vaccines is more inadequate in individuals with multimorbidity.

Factors Associated with SARS-CoV-2 Infection before Vaccination among European Health Care Workers.

BACKGROUND: Health care workers (HCWs) were on the frontline of the current pandemic. We aimed at identifying determinants of SARS-CoV-2 infection and the effectiveness of personal protection equipment (PPE) worn by HCWs before vaccination. METHODS: We abstracted data on SARS-CoV-2 infection based on positive PCR results and sociodemographic characteristics of 38,793 HCWs from public hospitals and public health authorities from 10 European centers. We fitted cohort-specific multivariate logistic regression models to identify determinants of infection and combined the results using random-effects meta-analyses. RESULTS: The overall prevalence of infection before vaccination among HCWs was 9.58%. Infection was associated with the presence of selected symptoms; no association was found between sociodemographic factors and increased risk of infection. The use of PPE and particularly FFP2/FFP3 masks had a different protective effect during the first and second waves of the COVID pandemic. CONCLUSIONS: The study provides evidence that mask use was the most effective PPE in preventing SARS-CoV-2 infection among HCWs.

Navafenterol for chronic obstructive pulmonary disease therapy.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a prevalent disease of the airways in which inhaled bronchodilators can be given as monotherapy or fixed dose combination, in order to better control disease symptoms and to reduce its morbidity. A novel bronchodilator approach is represented by bifunctional molecules such as navafenterol, which exert dual synergic bronchodilator effects as a monotherapy. Navafenterol is currently being investigated for COPD. AREAS COVERED: This review summarizes the preclinical data regarding navafenterol synthesis and in vitro and in vivo testing. Clinical data coming from phase I and II studies are also discussed. Navafenterol was found to improve lung function, dyspnea, and cough severity and was well tolerated, and its effect was comparable with that of fixed-dose combinations in patients with moderate-to-severe COPD. EXPERT OPINION: Despite clinical evidence of efficacy for navafenterol is still limited, the existing data prompts further clinical evaluation and also consideration of other inhalation approaches such as pressure metered-dose inhalers (pMDIs) or nebulization. Other interesting approach would be combination with another bifunctional molecule such as ensifentrine.

Challenges in Diagnosing Occupational Chronic Obstructive Pulmonary Disease.

Occupational chronic obstructive pulmonary disease (oCOPD) represents 15-20% of the global burden of this disease. Even if industrial bronchitis has long been known, new occupational hazards continue to emerge and enlarge the number of people exposed to risk. This review discusses the challenges related to the early detection of oCOPD, in the context of new exposures and of limited usage of methods for an efficient disease occupational screening. It underlines that a better translation into clinical practice of the new methods for lung function impairment measurements, imaging techniques, or the use of serum or exhaled breath inflammation biomarkers could add significant value in the early detection of oCOPD. Such an approach would increase the chance to stop exposure at an earlier moment and to prevent or at least slow down the further deterioration of the lung function as a result of exposure to occupational (inhaled) hazards.

Adiponectin and Asthma: Knowns, Unknowns and Controversies.

Adiponectin is an adipokine associated with the healthy obese phenotype. Adiponectin increases insulin sensitivity and has cardio and vascular protection actions. Studies related to adiponectin, a modulator of the innate and acquired immunity response, have suggested a role of this molecule in asthma. Studies based on various asthma animal models and on the key cells involved in the allergic response have provided important insights about this relation. Some of them indicated protection and others reversed the balance towards negative effects. Many of them described the cellular pathways activated by adiponectin, which are potentially beneficial for asthma prevention or for reduction in the risk of exacerbations. However, conclusive proofs about their efficiency still need to be provided. In this article, we will, briefly, present the general actions of adiponectin and the epidemiological studies supporting the relation with asthma. The main focus of the current review is on the mechanisms of adiponectin and the impact on the pathobiology of asthma. From this perspective, we will provide arguments for and against the positive influence of this molecule in asthma, also indicating the controversies and sketching out the potential directions of research to complete the picture.

Modified Plasma Cytokine Profile in Occupational Dermatitis.

BACKGROUND: Despite significant progress in the diagnosis of contact dermatitis, the identification by specific tests or biomarkers remains an unsolved issue, particularly when needed for the confirmation of the occupational origin of the disease. OBJECTIVE: To characterize the plasma proteome profile in occupational dermatitis in workers of paint industry. METHODS: The study has a case-control design, comparing exposed workers with and without occupational contact dermatitis, matched for age, gender, occupational history, and comorbidities. An immunological assay (Human XL Cytokine Array Kit - ARY022B, R&D Systems) was used to measure the plasma levels of 105 cytokines and chemokines in a pooled sample of the cases and a pooled sample of the controls. RESULTS: A 1.5-fold increase was noticed for interleukin 3, interleukin 10, and leptin in cases, as compared to controls. Fibroblast growth factor-7 and growth/differentiation factor-15 showed a 1.4-fold increase, while interleukin 19, interleukin 31, and macrophage inflammatory protein 3a.had only a 1.3- fold increase. The leukemia inhibitory factor was the only plasma cytokine that showed a 1.3-fold decrease. All other cytokines had a variation of less than 1.2-fold between cases and controls. CONCLUSION: The recognition of the molecular signatures is very important for an accurate and indisputable diagnosis of occupational contact dermatitis. In workers from the paint industry, plasma levels of interleukins 3, 10, 13 and 19, fibroblast growth factor-7, and growth/differentiation factor-15, together with leukemia inducible factor, may differentiate subjects with contact dermatitis from those without skin lesions.

Vitamin D Intake and Obesity in Occupational Asthma Patients and the Need for Supplementation.

BACKGROUND: Occupational asthma occurs in a significant number of adult unset forms of asthma. Even after exposure cessation, persistent asthma is frequent. Although recognized as important, nutrition, specifically vitamin D intake, was rarely evaluated in occupational asthma. OBJECTIVE: To assess the vitamin D intake in occupational asthma patients and the relation with body mass index, co-morbidities related to vitamin D deficit, lung function and quality of life. RESULTS: We found a reduced vitamin D intake in both irritant and allergic asthma, in obese and nonobese patients. The average intake in non-obese patients, although higher, did not reach statistical significance. We also found lower vitamin D intake in the mild asthma group versus the severe group, marginally reaching the significance level (p=0.056) at the median test. Regression analysis in asthma subpopulations revealed a different pattern of correlation, with a stronger relationship between the BMI and the impact score in irritant asthma and a closer link between vitamin D intake and symptoms score (p= 0.027) in the allergic asthma group. CONCLUSION: The relation between obesity and vitamin D on clinical scores and lung function seems to be different according to the asthma phenotype. However, our study supports the usefulness of nutritional interventions in all occupational asthma patients, targeting both the reduction of the fat mass and the achievement of the recommended daily intake of vitamin D. When analyzing the impact of the weight loss effect on asthma evolution, the vitamin D status should also be considered as an influencer.

Occupational exposure to urinary bladder carcinogens - risk factors, molecular mechanisms and biomarkers.

Bladder cancer (BC) is one of the most frequent forms of cancer, particularly in Caucasian population. Many environmental factors are recognized as carcinogenic in humans for this form of neoplasia and some of them are related to occupation. In order to illustrate these effects, we have selected several relevant cases with smoking and occupational exposure to carcinogens and their histopathological findings. We reviewed the most important research published in the field of environmental-genomic interaction in relation with the oncogenesis of BC. Three main directions have been identified and described in the article: the environmental factors involved in BC pathogenesis and evolution, the molecular mechanisms involved in cell mitosis control and xenobiotic metabolism related to the qualitative and quantitative exposure and, finally, the possible biomarkers of the tumor evolution. From the genomic and proteomic research, new biomarkers emerged that are in the validation process. Immunohistochemical methods open also new perspectives to the diagnostic algorithms and could serve as prognosis biomarkers.

Distinction between mesothelioma and lung adenocarcinoma based on immunohistochemistry in a patient with asbestos bodies in bronchoalveolar fluid - case report.

Asbestos is a mineral-mined form the rocks, consisting in amosite (brown asbestos), crocidolite (blue asbestos) and÷or chrysotile (white asbestos) used in many industries. Researches about the exposure to asbestos dust and asbestosis related diseases started almost a century ago. The first case report of fatal asbestosis disease was published in 1906, in England, by Dr. Hubert Montague Murray. A decade after, asbestos "curious bodies" were firstly described in the lung tissue by Cooke (1926) and McDonald (1927). Occupational exposure to asbestos is now regulated in Romania, but past exposure is still a cause of asbestosis-related diseases (ARDs), including lung cancer. A peculiar association between a lung adenocarcinoma, a previously healed pulmonary tuberculosis (PTB) disease, is reported in a 61-year-old nonsmoker white man, a former factory worker with 29 years of occupational exposure history to cement and asbestos fibers. The positive diagnosis of asbestos exposure was facilitated by asbestos bodies determined in bronchoalveolar lavage fluid. The main purpose of this case report is to describe the development of a right pleural effusion which was not revelatory for a mesothelioma but for an adenocarcinoma of the lung. An accurate morphologic and immunohistochemistry assessment of a pleural biopsy sample excluded mesothelioma and was crucial in the positive diagnosis of adenocarcinoma. In conclusion, unilateral paraneoplastic pleural effusion in a nonsmoker male with occupational exposure to asbestosis fibers was suggestive for adenocarcinoma related asbestosis of the lung. Lung cancer and malignant pleural exudate developed after a long latency cumulative retention time of asbestos fibers.

Interrelationship Between Pathophysiological Mechanisms of Vitamin D Deficit and Chronic Obstructive Pulmonary Disease.

Several similarities have reported between patients suboptimal level of vitamin D and patients with Chronic Obstructive Pulmonary Disease (COPD): both conditions are more prevalent after the 6th decade and are associated with impaired defense mechanisms, with skeletal muscles dysfunction and with an early ageing process. We have reviewed the literature concerning the interrelationship between the main pathophysiological processes of both conditions, in order to emphasize the influence of vitamin D deficit on COPD development and evolution. Epidemiological, clinical and experimental data supporting this association are presented. We concluded that the identification of common pathophysiological mechanisms for the vitamin D deficiency and COPD substantiates the hypothesis of the involvement of this hormone in the chronic obstructive pulmonary disease.

Obstructive Sleep Apnea Syndrome in a Railroad Controller Worker.

Sleep Apnea Syndrome (SAS) constitutes a healthcare issue of major importance at international level with a prevalence of 5% in the active population. Consequentially to the induced co-morbidities, the mortality reaches as high as 39% at eight years time lapse from the initial diagnostic. Seldom undiagnosed, the severity spectrum of SAS, in the absence of therapy, only continues to amplify. Here below, we are presenting the case of a 49 years old patient, railroad controller worker, non-smoker and occasionally alcohol user, who was hospitalized in our Clinic for Occupational Medicine. During last year, the patient was accusing excessive daytime somnolence, breath arrests during sleep, intense snoring, morning headaches, morning oral dryness, pin point chest pain, nocturia (4-5 nocturnal urination), concentration difficulties and an overall reduced work capacity. The presumptive diagnostic of Obstructive Sleep Apnea is being considered based on the correlation between the clinical presentation and the Epworth, Stanford and Berlin questionnaire results. The key diagnostic element was the polygraph recording over an 8 hours sleep period. Positive Diagnosis: Obstructive Sleep Apnea severe form. Management and recommendations: (1) Behavioral therapy (weight loss) and (2) CPAP (Continuous Positive Airway Pressure) therapy which was instituted immediately after the positive diagnosis was made. As a consequence, the respiratory symptoms, the frequent episodes of daytime snoozing and the concentration difficulties at work place diminished considerably.

Role of comorbidities in caring for chronicly ill elderly patients with and without dementia.

BACKGROUND AND AIM: The aim of this study is to highlight the presence of co-morbidities and their role in caring for chronicly ill patients with and without dementia. PATIENTS AND METHODS: The study was performed on a group of 213 chronic patients. We used CIRS-G (Cumulative Illness Rating Scale in Geriatric Population) and IADL (Instrumental Activity Daily Living) scales. We compared the scores of severity and dependency. RESULTS: The most frequent co-morbidities in the study group were cardiac, vascular, locomotor, sensory organs and metabolic diseases. For the study group, the highest medium score of severity according to the CIRS-G scale was represented by cardiovascular diseases. For patients with dementia, psychiatric, cardiac, vascular, metabolic, genitourinary, sensory organs and locomotion domains had the highest score of severity and dependency. CONCLUSIONS: The health status of chronic patients with and without dementia is characterized by multiple pathologies with various degrees of severity and dependency.

[Information group--a solution to increase the efficacy of specialized intervention for smoking cessation]. / Grupul de informare--o solutie de crestere a eficacitatii consultatiei specializate pentru renuntarea la fumat.

Since 2007, in Romania, the Ministry of Health implements the national programme for tobacco control which contains also a sub-programme for sustaining smoking cessation through free treatment and counselling. Because the specialised intervention lasts too long (often more than 60 minutes) and the requests for support increased with a high rate, we had to identify methods to increase the efficacity of the intervention and, thus, the efficiency. According to this new situation, since January 2008, all the smokers asking for support to the Center for Smoking Cessation from the National Institute of Pneumology "Marius Nasta" had to participate to an "information group" prior to visit to the doctor or/and psychologist for specialized help. The aim of this group is to offer the common information needed by all smokers and does not have any elements of group therapy. During 1st January 2008 - 31st December 2009, 829 smokers asked for help in Bucharest centers, from which 585 addressed to the physicians and 288 to the psychologists, a percentage being referred to both specialists. The smokers who are going directly to the specialist tend to choose only one specialist (67,8% doctor and 24% psychologist); only 8,1% are going to both specialists. In the meantime, those smokers who are participating to the information group, are using the services of both counsellors: 30,8% comparing with 28,2% only to doctor and 9,4% only to psychologist. Comparing with the smokers who went directly to the doctor, the smokers who underwent the group of information had an increased succes rate at 3 months after quiting with 27,8%. Also, the percentage of "lost" persons decreased with 51%. Participation to the information group increases the likelihood of attendance to both specialists by 2,8 times. The common approach of the smoker increased the abstinence rate independently of the participation to the information group: 44% increase for smokers who participated to the information group, and 67,3% for persons that directly addressed to the physician. In conclusion, organising an information group will increase the double approach of the smoker (by physician and psychologist) which, in turn, will increase the success rate and the efficiency of the medical act.

[Diagnosis and management of occupational asthma in the American College of Chest Physicians statement]. / Diagnosticul si managementul astmului profesional prezentat de Consensul formulat de American College of Chest Physicians.

Occupational asthma is one of the most common work-related respiratory conditions and causes considerable morbidity and impairment of quality of life. In the general population, the occupations that contribute to asthma are concentrated in the construction industry, metal, plastic and rubber work, printing and industrial cleaning. The magnitude of the attributable risk of occupational asthma is estimate between 4 to 58% among all cases of asthma. The American College of Chest Physicians (ACCP) Consensus 2007 statement proposed to reveal how the practicing pulmonologist can know whether someone is exposed to an asthma inducer at work and how is it better to manage the diagnosis and control this disease. This current statement updates the first 1995 consensus of ACCP about professional asthma, including relevant to preventive measures and work exacerbated asthma.

Systemic dermatitis and obstructive respiratory syndrome following occupational sensitization to trichloroethylene.

We present a derma-respiratory syndrome in a patient occupationally exposed to trichloroethylene (TCE). At the beginning of its industrial use trichloroethylene was considered harmless. But, in time it showed a high noxious capacity. It produces an important and various pathology, which evolves as acute or chronic disease. The case we present shows that trichloroethylene can induce cutaneous pathology that excels contact dermatitis. It also proves that trichloroethylene can produce systemic effects (obstructive respiratory syndrome). The particularity of the case is based on the succession of the events, first the cutaneous and then the respiratory effects. A long period of time was necessary for the installation of the symptoms (for cutaneous and bronchial sensitization to take place). The case presented is the proof that trichloroethylene's great toxicity cannot be doubted and that the clinical forms due to sensitization to trichloroethylene can be dramatic.

Farmer's lung.

Farmer's lung is a well known occupational disease, described many years ago; the incidence in our country is still very low. That is the reason why we find interesting to make a review of the main diagnostic procedures and to present the new data in this form of hypersensitivity pneumonitis. Other farmers' occupational induced respiratory diseases are also presented, with their similitudes and their differences from the classical farmer's lung.