Lower Respiratory Tract Disease Research Articles

Is a Consensus Case Definition for Viral Associated Lower Respiratory Tract Disease (LRTD) in Clinical Trials Possible?

Lower respiratory tract illness or disease (LRTI/LRTD) represents a significant source of morbidity and mortality following viral respiratory illnesses, yet a consensus definition for this outcome is lacking. Recent studies of novel vaccines against respiratory syncytial virus (RSV) for older adults used LRTI/LRTD as the primary outcome to assess vaccine efficacy. However, the different vaccine trials have used highly variable criteria to define this outcome, leading to difficulty in comparison of vaccine efficacy results between trials. Here we review the key differences in criteria for case definitions, highlight strategies to best approximate compatibility between definitions, and review vaccine efficacy results among currently US Food and Drug Administration (FDA)-approved vaccines using these strategies. We hope this overview will support the need to develop a consensus definition for LRTI/LRTD to improve future research related to viral respiratory disease.

Current Review of Comorbidities in Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a heterogenous disease with a significant impact on patient quality of life and a substantial economic burden. CRS is associated with several systemic inflammatory conditions. We provide an updated review of CRS comorbidities as a springboard for future comorbidity mapping and potential therapeutics. The link between environmental allergies and CRS is most evident for central compartment atopic disease (CCAD) and allergic fungal rhinosinusitis (AFRS) subtypes but remains inconclusive for CRS overall. The association between asthma and CRS, reinforced by the unified airway theory, is evidenced by their response to similar biologic therapies. Another lower respiratory tract disease, COPD, has up to a 50% co-occurrence with CRS and warrants careful screening and treatment. Eosinophilic esophagitis and CRS share eosinophilic inflammation in different sites, meriting further research. Obesity not only presents physiological challenges but also correlates with a more severe subset of CRS. Diabetes mellitus is associated with CRSwNP, possibly secondary to therapeutics with steroids. Autoimmunity may contribute to nasal polyp formation through cytokines such as B-cell activating factor (BAFF), offering potential for future therapeutics. This review illustrates the need to employ a macroscopic approach in clinical decision making and treatment of CRS. Comorbidities may contribute to an overall proinflammatory state, magnify severity of symptoms, be a source of treatment resistance, and even an opportunity for future therapeutics.

Bovine respiratory disease: prevention and control

Bovine respiratory disease (BRD) presents a diagnostic challenge as clinical signs alone may not identify the underlying cause. Whilst clinical signs may suggest pneumonia, it is important to recognise that BRD encompasses upper and lower respiratory tract disease. Both bacterial and viral pathogens are implicated in BRD, and co-infections are common, further complicating diagnosis.

Prospective Attitudes Towards Respiratory Syncytial Virus (RSV) Vaccine in Pregnant Women in Greece

Respiratory Syncytial Virus (RSV) is a common respiratory pathogen with high morbidity and mortality, especially in children under two years of age. Severe RSV infection poses a significant threat to healthcare systems, making vaccination an utmost need. In August 2023, the U.S. FDA approved an RSV maternal vaccine to prevent lower respiratory tract disease (LRTD) in infants throughout their first six months of life. This cross-sectional survey was designed to evaluate pregnant women’s willingness to receive the vaccine during pregnancy. An anonymous survey was administered from April 2023 to December 2023 to pregnant women aged above 16 years old attending gynecology wards of randomly selected public and private hospitals in Crete. The primary outcome was the intention to receive the vaccine. Univariable and multivariable analyses were carried out to identify factors associated with the intention to get vaccinated. Questionnaires were distributed to a sample of 335 pregnant females who agreed to participate in this study. The intention to get vaccinated against RSV was positively associated with educational level, the presence of school-age children, RSV infection awareness, intention to get routine pregnancy vaccines according to the National Immunization Program (NIP), and previous vaccination against COVID-19. The majority of pregnant females were not familiar with the term RSV and the upcoming vaccine. An educational campaign regarding RSV infection and its vaccine is required to improve women’s perceptions and to support healthcare workers in promoting it upon its availability in Greece.

Bronchoalveolar lavage fluid and lung biopsy tissue metagenomic next-generation sequencing in the diagnosis of pulmonary cryptococcosis.

To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) in pulmonary cryptococcosis (PC) using bronchoalveolar lavage fluid (BALF) and lung biopsy tissue specimens. In this retrospective study, 321 patients diagnosed with lower respiratory tract diseases who underwent mNGS using BALF and LBT samples, between January 2021 and December 2023 were included. Individuals were classified into PC and non-PC groups according to the diagnostic criteria for PC, and conventional fungal cultures were performed. A serum/BALF cryptococcal antigen (CrAg) test was performed in some patients with PC. The diagnostic efficiencies of three methods for PC (mNGS, conventional culture, and CrAg) were compared. Additionally, two mNGS methods were used in this study: original mNGS (OmNGS, testing time from January 2021 to December 2022) and modified mNGS (MmNGS, testing time from January to December 2023). The diagnostic efficiency of the two mNGS methods on PC was simultaneously compared. Among the 321 patients, 23 (7.2%) had PC and 298 (92.8%) did not. Compared with the composite reference standard for PC diagnosis, the sensitivity, specificity, and accuracy of mNGS for PC were 78.3% (95% confidence interval [CI], 55.8%-91.7%), 98.7% (95% CI, 96.4%-99.6%), and 97.2% (95% CI, 94.7%-98.7%), respectively. The sensitivity of mNGS was similar to that of CrAg (80.0%, 12/15) (P > 0.05). The diagnostic sensitivity of both mNGS and CrAg was higher than that of conventional culture (35.0%, 7/20) (P = 0.006, P = 0.016), and the combined detection of mNGS and CrAg further improved the diagnostic sensitivity of PC (93.3%, 14/15). The area under the receiver operating characteristic curve of mNGS was superior to that of conventional culture (0.885 vs. 0.675). In addition, the diagnostic sensitivity of PC was higher than that of OmNGS (P = 0.046). The sensitivity of mNGS is better than that of conventional culture. The combination of mNGS and CrAg improves the testing sensitivity of Cryptococcus. MmNGS could further improve the detection of Cryptococcus. Conventional PC detection methods are indispensable and mNGS can be used as a rapid and accurate auxiliary diagnostic method for PC.

Cost-effectiveness of respiratory syncytial virus adjuvanted vaccine in Portuguese aged ≥ 60 years

Abstract Background Respiratory syncytial virus (RSV) infections are one of the leading causes of lower respiratory tract disease among adults aged ≥60 years in Europe. This study aims to assess the potential public health impact of the RSVPreF3 OA adjuvanted vaccine, the first approved preventive intervention for the older adult population in Portugal. Methods A monthly-cycle static Markov model was developed to assess RSVPreF3 OA adjuvanted vaccine impact on adults aged 60 years and older in Portugal. A single dose of RSVPreF3 OA adjuvanted vaccine was compared to no-vaccination over a three-year time-horizon. The model captures lower respiratory tract disease (LRTD) RSV cases, hospitalizations, deaths, and healthcare resource utilization. Data inputs were based on local published literature, supplemented by the best available data when local information was lacking. Results Based on preliminary analysis considering 75% vaccine coverage, model outputs estimate that RSVPreF3 OA adjuvanted vaccine can prevent 71,433 LRTD cases requiring medical attendance, 11,067 hospitalizations, 1,793 intensive care unit admissions and 1,003 deaths. The model estimates that 32 adults need to be vaccinated to avoid one RSV LRTD case, 207 adults need to be vaccinated to avoid one hospitalization and 2,283 adults need to be vaccinated to avoid one death. The incremental cost-effectiveness ratio was estimated at 9,541€, hence the RSVPreF3 OA adjuvanted vaccine is cost-effective compared to no vaccination. Conclusions The results demonstrate a strong preventive impact of the RSVPreF3 OA adjuvanted vaccine on health outcomes and healthcare resource utilization in adults ≥60 years, leading to a significant public health benefit. This result emphasizes the importance of preventing RSV to preserve the health and well-being of Portugal’s older adults. In addition, data from ongoing studies may enhance precision and extensive sensitivity analyses validate the robustness of the model’s input assumptions. Key messages • This study shows the robust evidence of RSVPreF3 OA adjuvanted vaccine to improve public health by preventing thousands of hospitalizations and deaths among ≥60 years, in Portugal. • Vaccinating adults aged ≥ 60 years with RSVPreF3 OA adjuvanted vaccine in Portugal is a cost-effective strategy.

A multivalent RSV vaccine based on the modified vaccinia Ankara vector shows moderate protection against disease caused by RSV in older adults in a phase 3 clinical study

Respiratory syncytial virus (RSV) causes a significant disease burden in older adults. The live recombinant vaccine based on a nonreplicating modified vaccinia Ankara (MVA-BN) poxvirus, MVA-BN-RSV, encoding for multiple proteins of RSV subtypes A and B, was assessed for efficacy against respiratory disease caused by RSV.Adults aged ≥60 years, with or without underlying chronic conditions, were enrolled and randomized in a 1:1 ratio to receive a single dose of vaccine or placebo and were followed for disease caused by RSV infection during the 2022–2023 season. The 2 primary endpoints were RSV-associated lower respiratory tract disease (LRTD) with ≥3 and ≥ 2 symptoms; acute respiratory disease (ARD) was a key secondary endpoint. The humoral RSV-specific immune response was assessed at baseline and 14 days post-vaccination. Safety was evaluated by collection of solicited adverse events (AEs) and unsolicited AEs for 7 and 28 days post-vaccination respectively, and SAEs for the entire study period.In total, 18,348 participants were included in the final efficacy and safety analyses. Vaccine efficacy was 42.9 % (95 % CI: −16.1; 71.9) against RSV-associated LRTD with ≥3 symptoms, 59.0 % (95 % CI: 34.7; 74.3) against LRTD with ≥2 symptoms, and 48.8 % (95 % CI: 25.8; 64.7) against ARD. The primary objective was not met for LRTD with ≥3 symptoms since the lower bound of the 95 % CI was below 20 %, the prespecified success criterion. The vaccine-elicited immune response showed mean fold-increases of 1.7 for RSV A and B neutralizing antibodies and 2.9 and 4.3 for RSV-specific IgG and IgA, respectively. The vaccine displayed mild to moderate reactogenicity, and no safety concerns were identified.MVA-BN-RSV induced suboptimal protection against RSV-associated LRTD, likely due to suboptimal neutralizing antibody response. The vaccine had an acceptable safety profile and confirmed immunogenicity, overall showing promise for MVA-BN-vectored constructs targeting other diseases.Trial Registration:Clinicaltrials.gov Identifier NCT05238025 (Registered February 14, 2022).

Epidemiology of human metapneumovirus in Taiwan from 2013 to 2023

Human metapneumovirus (HMPV) is a member of the genus Metapneumovirus in the family Pneumoviridae of the order Mononegavirales that can cause upper and lower respiratory tract disease. This retrospective study describes the epidemiology of hMPV based on community viral surveillance results from sentinel sites across Taiwan from 2013 to 2023. A total of 114 hMPV strains were isolated and analyzed to assess viral evolution through sequencing of their fusion protein genes. This study revealed that hMPV cases occur almost year-round in Taiwan, with a peak occurring during spring (March to May). Of the 114 infected patients, 68.4% were children under 4 years old. The geographical distribution of hMPV positivity was highest in Penghu County, followed by Changhua County and Hsinchu County. The clinical symptoms of hMPV infection are nonspecific, with fever (56.1%), cough (44.7%), rhinorrhea (21.1%), and sore throat (14.9%) being the most common. However, a few patients also developed severe central nervous system symptoms (1.8%) or dyspnea (0.9%). Phylogenetic analysis revealed genetic diversity among the 114 isolated hMPV strains, with the A2 lineage (57.9%) being the most frequently observed, followed by the B2 lineage (33.3%), in the Taiwanese community from 2013 to 2023. In conclusion, hMPV causes a serious acute respiratory disease in Taiwan that should not be neglected. Further epidemiological surveillance and investigations of the clinical characteristics of hMPV should be performed continually for prevention and control of this virus.

A new RSV vaccine (mResvia) for adults ≥60 years old.

The FDA has licensed mResvia (Moderna), an mRNA respiratory syncytial virus (RSV) vaccine, for prevention of lower respiratory tract disease (LRTD) caused by RSV in adults ≥60 years old. It is the first mRNA vaccine to be licensed in the US for this indication. Two recombinant RSV vaccines, Arexvy and Abrysvo, are also available for prevention of RSV LRTD.1 Arexvy is approved for use in adults ≥50 years old.2 Abrysvo is approved for use in adults ≥60 years old and in pregnant women to prevent RSV LRTD in their infants.

Antibody-mediated protection against respiratory syncytial virus in children.

Respiratory syncytial virus (RSV) is a major global pathogen, causing lower respiratory tract disease in at-risk populations including young children. Antibodies form a crucial layer of protection from RSV disease, particularly in immunologically naïve infants. Such antibodies are derived from the mother via transplacental transfer and breast milk, but may be particularly low in high-risk infants such as those born preterm. Maternally derived antibodies can now be supplemented by the administration of anti-RSV monoclonal antibodies, while a rising wave of maternal and paediatric vaccine strategies are approaching. The implementation of these prophylactics may profoundly decrease the healthcare burden of RSV. In this article, we review the role of antibody-mediated immunity in protecting children from RSV. We focus on maternally derived antibodies as the main source of protection against RSV and study factors that influence the scale of this transfer. The role of passive and active prophylactic approaches in protecting infants against RSV are discussed and knowledge gaps in our understanding of antibody-mediated protection against RSV are identified.

Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years and older in the USA, October, 2023, to March, 2024: a test-negative design analysis

Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years. We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region. Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71-85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52-92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48-85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70-83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type. Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023-24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved. The Centers for Disease Control and Prevention.

The importance of choosing a mucoregulator in the treatment of cough in case of upper and lower respiratory tract diseases. Experience of use and perspectives of carbocysteine therapy

The importance of choosing a mucoregulator in the treatment of cough in case of upper and lower respiratory tract diseases. Experience of use and perspectives of carbocysteine therapy

Development and testing of a deep learning algorithm to detect lung consolidation among children with pneumonia using hand-held ultrasound.

Severe pneumonia is the leading cause of death among young children worldwide, disproportionately impacting children who lack access to advanced diagnostic imaging. Here our objectives were to develop and test the accuracy of an artificial intelligence algorithm for detecting features of pulmonary consolidation on point-of-care lung ultrasounds among hospitalized children. This was a prospective, multicenter center study conducted at academic Emergency Department and Pediatric inpatient or intensive care units between 2018-2020. Pediatric participants from 18 months to 17 years old with suspicion of lower respiratory tract infection were enrolled. Bedside lung ultrasounds were performed using a Philips handheld Lumify C5-2 transducer and standardized protocol to collect video loops from twelve lung zones, and lung features at both the video and frame levels annotated. Data from both affected and unaffected lung fields were split at the participant level into training, tuning, and holdout sets used to train, tune hyperparameters, and test an algorithm for detection of consolidation features. Data collected from adults with lower respiratory tract disease were added to enrich the training set. Algorithm performance at the video level to detect consolidation on lung ultrasound was determined using reference standard diagnosis of positive or negative pneumonia derived from clinical data. Data from 107 pediatric participants yielded 117 unique exams and contributed 604 positive and 589 negative videos for consolidation that were utilized for the algorithm development process. Overall accuracy for the model for identification and localization of consolidation was 88.5%, with sensitivity 88%, specificity 89%, positive predictive value 89%, and negative predictive value 87%. Our algorithm demonstrated high accuracy for identification of consolidation features on pediatric chest ultrasound in children with pneumonia. Automated diagnostic support on an ultraportable point-of-care device has important implications for global health, particularly in austere settings.

Nirsevimab for prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants.

Nirsevimab for prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants.

Efficacy and safety of vaccines to prevent respiratory syncytial virus infection in infants and older adults: A systematic review and meta-analysis

ObjectivesTo determine the efficacy and safety of respiratory syncytial virus (RSV) vaccines in infants and older adults. MethodsWe performed a systematic review and meta-analysis of randomized control trials that evaluated the efficacy of maternal RSV immunization against infections in infants, as well as the efficacy of RSV vaccines in older adults. The primary outcome was the vaccine efficacy against RSV-related lower respiratory tract disease (LRTD). Grading of Recommendations Assessment, Development and Evaluation criteria was used to evaluate the level of evidence. ResultsTen trials were included in the review. For maternal vaccination, the RSV vaccine showed favourable efficacy against RSV-related LRTD (vaccine efficacy 57.3%, 95% confidence interval [CI] 31.3-73.5; low certainty) and RSV-related severe LRTD (vaccine efficacy 81.9%, 95% CI 56.8-92.4; moderate certainty) in infants within 90 days after birth. For older adults, Meta-analysis showed that RSV vaccines could also reduce the risk of RSV-related LRTD (vaccine efficacy 78.3%, 95% CI 65.6-86.3; moderate certainty) and RSV-related severe LRTD (vaccine efficacy 86.5%, 95% CI 68.3-94.3; moderate certainty). There was no significant difference in serious adverse events between RSV vaccines and placebo. ConclusionRSV vaccines have the potential to offer protection against RSV disease in both infants and older adults, without apparent safety concerns.

Comprehensive Summary of Safety Data on Nirsevimab in Infants and Children from All Pivotal Randomized Clinical Trials.

Nirsevimab is approved in the US for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season and in children aged ≤24 months who remain vulnerable to severe RSV disease through their second RSV season. We summarize a pre-specified analysis of nirsevimab safety data from three randomized controlled trials: Phase 2b (NCT02878330; healthy infants born ≥29 to <35 weeks' gestational age [wGA]); Phase 3 MELODY (NCT03979313; healthy infants born ≥35 wGA); and Phase 2/3 MEDLEY (NCT03959488; infants with congenital heart disease [CHD] and/or chronic lung disease of prematurity [CLD] or born ≤35 wGA). Participants (randomized 2:1) received a single intramuscular dose of nirsevimab or comparator (placebo, Phase 2b/MELODY; 5× once-monthly palivizumab, MEDLEY) before their first RSV season (recipients < 5 kg, nirsevimab 50 mg; ≥5 kg, nirsevimab 100 mg). In MEDLEY, children with CHD/CLD continued to a second RSV season: first-season nirsevimab recipients received nirsevimab 200 mg; first-season palivizumab recipients were re-randomized 1:1 to receive nirsevimab 200 mg or 5× once-monthly palivizumab. The incidence, severity, and nature of AEs were similar across treatments (nirsevimab, n = 3184; placebo, n = 1284; palivizumab, n = 304). Most AEs were mild to moderate in severity, with ≥98% unrelated to treatment. AEs of special interest occurred infrequently (<1%): no anaphylaxis or thrombocytopenia were treatment-related, and no immune complex disease was reported. Deaths (incidence < 1.0%) were all unrelated to treatment. A single dose per season of nirsevimab for the prevention of RSV disease had a favorable safety profile, irrespective of wGA or comorbidities.

Impact of Nirsevimab Immunization on Pediatric Hospitalization Rates: A Systematic Review and Meta-Analysis (2024).

A systematic review with a meta-analysis was performed to gather available evidence on the effectiveness of monoclonal antibody nirsevimab in the prevention of lower respiratory tract diseases (LRTDs) due to respiratory syncytial virus (RSV) in children and newborns (CRD42024540669). Studies reporting on real-world experience and randomized controlled trials (RCTs) were searched for in three databases (PubMed, Embase, and Scopus) until 1 May 2024. Our analysis included five RCTs, seven real-world reports, and one official report from the health authorities. Due to the cross-reporting of RCTs and the inclusion of multiple series in a single study, the meta-analysis was performed on 45,238 infants from 19 series. The meta-analysis documented a pooled immunization efficacy of 88.40% (95% confidence interval (95% CI) from 84.70 to 91.21) on the occurrence of hospital admission due to RSV, with moderate heterogeneity (I2 24.3%, 95% CI 0.0 to 56.6). Immunization efficacy decreased with the overall length of the observation time (Spearman's r = -0.546, p = 0.016), and the risk of breakthrough infections was substantially greater in studies with observation times ≥150 days compared to studies lasting <150 days (risk ratio 2.170, 95% CI 1.860 to 2.532). However, the effect of observation time in meta-regression analysis was conflicting (β = 0.001, 95% CI -0.001 to 0.002; p = 0.092). In conclusion, the delivery of nirsevimab was quite effective in preventing hospital admissions due to LRTDs. However, further analyses of the whole RSV season are required before tailoring specific public health interventions.

Use of inhaled solution of hypertonic saline combined with high-molecular-weight hyaluronic acid in patients with lower respiratory tract diseases

Resolution of the Council of ExpertsNovember 17, 2023Respiratory diseases (acute and chronic bronchitis, chronic obstructive pulmonary disease (COPD), bronchiectasis, cystic fibrosis (CF), bronchial asthma, etc.) are often accompanied by impaired mucus clearance. In this regard, mucoactive drugs are most commonly used for the treatment. Hypertonic saline plus high-molecular-weight hyaluronic acid is one of the affordable and effective agents that can help with thinning and removal of bronchial secretions. The effect of 3%, 6%, 7% hypertonic saline on the respiratory system is multifaceted: it stimulates the osmotic fluid flow, breaks bonds linking polymers in the sputum, reduces swelling in the mucous membranes, stimulates ciliary beat frequency, and reduces the neutrophilic inflammation severity. The molecular size of HA plays an important role in the effectiveness of inhalation therapy with hypertonic saline combined with hyaluronic acid (HA). External administration of high-molecular-weight hyaluronic acid inhibits neutrophil elastase and metalloproteinase, potentiates hydration of bronchial secretions and has anti-inflammatory properties. In addition to clinical studies, real-life clinical practice in patients with cystic fibrosis, bronchiectasis and acute bronchitis also demonstrated the effectiveness of hypertonic saline combined with high-molecular-weight hyaluronic acid. The rationale for the use of hypertonic saline was reflected in the international GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines in 2023. Therefore, due to high interest in the hypertonic saline combined with high-molecular-weight hyaluronic acid, it is important to expand the evidence base: to initiate a Russian multicenter study evaluating the effectiveness and safety of this combination in patients with chronic bronchitis and COPD in the Russian Federation. It will allow us to recommend hypertonic saline combined with high-molecular-weight hyaluronic acid to be included in the Russian clinical guidelines on treatment of chronic bronchitis and COPD as a mucoactive drug.

АНАЛИЗ ВЛИЯНИЯ ОБЛУЧЕНИЯ НА МУЛЬТИМОРБИДНОСТЬ УЧАСТНИКОВ ЛИКВИДАЦИИ ПОСЛЕДСТВИЙ АВАРИИ НА ЧЕРНОБЫЛЬСКОЙ АЭС

Purpose: To give a general idea of the most common combinations of diseases in the male population of the Russian Federation and to identify the combinations of diseases, the development of which could be influenced by ionising radiation. Material and methods: Cohort study of the influence of external gamma irradiation on multimorbidity of the Chernobyl accident liquidation participants according to the data of the National Radiation Epidemiological Registry. Multimorbidity was defined as the presence in one participant of the cohort of two or more diseases from the list consisting of ten groups of diagnoses: diseases of lower respiratory tract, diseases of musculoskeletal system, diseases of endocrine system, mental disorders, oncology, neurology, diseases of digestive organs, diseases of cardiovascular system, diseases of genitourinary system, diseases of sense organs. The cohort consisted of men born between 1919 and 1969 who worked in the accident zone from 1986 to 1987 and had a documented whole-body external gamma dose. Cohort follow-up period: 1992–2021. The cohort size at the beginning of the follow-up was 59 290 people. The study participants were divided into two groups according to external gamma dose: up to 150 mGy – 34602 individuals, 150 mGy and more – 24 688 individuals. For all possible combinations of diagnoses, relative radiation risk was calculated as a measure of the association of exposure with diseases. The relative radiation risk was considered statistically significant if the left border of the one-sided 95 % confidence interval was greater than 1. Statistical analyses were performed using the R programming language for statistical computing and the R arules package. Results: During 30 years of follow-up, multimorbidity was noted in 62 % of individuals. The most common combinations of chronic diseases were combinations of cardiovascular diseases with digestive diseases (23 % of the original cohort), with lower respiratory diseases (22 %) and with musculoskeletal diseases (18 %). A combination of all four diagnosis groups was identified in 5 % of individuals. Nineteen multimorbid combinations with statistically significant relative radiation risk in the range (1.07–1.23) were identified. Conclusions: No effect of radiation exposure on the number of individuals with multimorbidity was found, but in the studied cohort there are individuals with cardiovascular diseases, endocrine diseases, oncology and combinations of these groups of diagnoses with diseases of other body systems may be caused by radiation exposure. The statistically significant relative radiation risk for combinations of diagnoses is, in general, greater than for the individual diseases that make up these combinations.

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Single Vaccination of Ad26.RSV.preF-Based Regimen in Japanese Adults Aged 60 Years and Older.

Respiratory syncytial virus (RSV) is increasingly recognized as a significant cause of lower respiratory tract disease (LRTD) in older adults. The Ad26.RSV.preF/RSV preF protein vaccine demonstrated protective efficacy against RSV related LRTD in a Phase 2b study in the United States. Hence, Ad26.RSV.preF/RSV preF protein vaccine candidate was evaluated in the Japanese older adult population. This Phase 1 study evaluated safety, reactogenicity, and immunogenicity of Ad26.RSV.preF/RSV preF protein vaccine at dose level of 1 × 1011 vp/150 μg in Japanese healthy adult aged ≥60 years. The study included a screening Phase, vaccination, 28-day follow up Phase, a 182-day follow-up period, and final visit on Day 183. A total of 36 participants were randomized in a 2:1 ratio to receive Ad26.RSV.preF/RSV preF protein vaccine (n = 24) or placebo (n = 12). After study intervention administration, the safety and immunogenicity analysis were performed as per planned schedule. Immune responses including virus-neutralizing and preF-specific binding antibodies were measured on Days 1, 15, 29, and 183. There were no deaths, SAEs, or AEs leading to discontinuation reported during the study. The Ad26.RSV.preF/RSV preF protein vaccine had acceptable safety and tolerability profile with no safety concern in Japanese older adults. The Ad26.RSV.preF/RSV preF protein vaccine induced RSV-specific humoral immunity, with increase in antibody titers on Days 15 and 29 compared with baseline which was well maintained until Day 183. A single dose of Ad26.RSV.preF/RSV preF protein vaccine had an acceptable safety and tolerability profile and induced RSV-specific humoral immunity in Japanese healthy adults. NCT number: NCT04354480; Clinical Registry number: CR108768.