Lower Respiratory Infections Research Articles

Burkholderia Cenocepacia MALDI-ToF Mass Spectra in the Assessing the Course of Lower Respiratory Tract Infection in Patients with Cystic Fibrosis

Burkholderia Cenocepacia MALDI-ToF Mass Spectra in the Assessing the Course of Lower Respiratory Tract Infection in Patients with Cystic Fibrosis

Mortality Associated with Infectious Diseases in Dutch Nursing Homes

BackgroundAlthough older people in nursing homes have a larger susceptibility to infectious diseases, the extent to which infectious diseases contribute to their mortality is unknown. Therefore, we quantified the associations between seasonal infectious diseases and all-cause mortality in Dutch nursing homes. MethodsWe analyzed time series (January 2009 to December 2021) of the weekly sentinel surveillance of infectious diseases in Dutch nursing homes. A generalized linear model with binomial distribution and identity link was used to associate the proportion of all-cause mortality with the incidence of infections: COVID-19 (2020–2021), gastroenteritis (GE), influenza-like illness (ILI), and lower respiratory tract infections (LRTIs) at 0- to 4-week time-lags (mortality incidence at 0 to 4 weeks after infections incidence). ResultsOver 13 years, 81 nursing homes participated, with 20 to 35 homes each year (mean: 26). A total of 11,555 all-cause deaths occurred over 1,864,667 resident weeks, averaging a mortality incidence of 6.2 per 1000 resident weeks. All 4 tested infectious diseases exhibited a significant association with all-cause mortality in nursing homes (P ≤ .01). Collectively, these infectious diseases were associated with 18.6% (95% CI, 17.8%–19.3%) of all deaths. The association between mortality and ILI was significant in 7 of 12 ILI seasons. Yearly mortality associated with the specific infectious diseases was as follows: LRTI (10.2%; 95% CI, 9.6%–10.8%), ILI (8.2%; 95% CI, 7.5%–8.9%) (over the 7 of 12 significant seasons), COVID-19 (6.5%; 95% CI, 5.4%–7.7%) (over 2019–2021 as there was no previous SARS-CoV-2 circulation), and GE (2.3%; 95% CI, 2.0%–2.5%). Conclusion and ImplicationsIn nursing homes, the occurrence of seasonal respiratory and gastrointestinal infections is associated with nearly one-fifth of all-cause deaths. Although infection prevention and surveillance may already be performed in some nursing homes, it is vital to implement, and enhance targeted strategies like (hand) hygiene protocols, environmental cleaning practices, reducing droplet and aerosol transmission, and vaccination to effectively address specific infections.

Pediatric hemoptysis: diagnostic and interventional challenges.

Hemoptysis in the pediatric population, while infrequent, poses significant challenges for both the family and healthcare practitioners. The severity of hemoptysis dictates management decisions. Most cases being mild and self-limiting are treated conservatively. However, "life-threatening hemoptysis" may occur, and is defined as any degree of blood loss that endangers the airway and is arbitrarily considered to be > 8ml/kg in 24h in children. It requires prompt airway management and resuscitation followed by a tailored approach consisting of bronchoscopy, computed tomography (CT), interventional radiology, and/or surgery depending on the patient 's clinical status and cardiopulmonary comorbidities. Bronchial arteries are hypertrophied in myriad conditions and account for 90-95% cases of hemoptysis due to their systemic pressure levels; the rest being contributed by pulmonary artery pathologies. Despite similar pathogenic mechanisms, the etiologies of pediatric hemoptysis differ from those in adults, with acute lower respiratory tract infections being the predominant cause. Imaging plays a crucial role in identifying the source and cause of hemorrhage. Multidetector computed tomography (MDCT) has emerged as a prime modality in the diagnostic evaluation of hemoptysis and provides a roadmap for potential interventional procedures. This article discusses the etiopathogenesis of hemoptysis along with a brief mention of the diagnostic modalities. It provides a structured reporting format and uses it to illustrate the imaging features in hemoptysis, with emphasis on CT angiography. The key findings in the lung parenchyma, airways, bronchial and non-bronchial systemic collaterals, and pulmonary arteries are elaborated upon. It further addresses the nuances of interventional management, particularly emphasizing the applications of bronchial artery embolization and pulmonary artery embolization in the pediatric population. The article also underscores the potential complications and factors influencing recurrence rates.

Burden of respiratory syncytial virus infections in older adults with acute respiratory infection in Japan: An epidemiological study among outpatients

BackgroundRespiratory syncytial virus (RSV) is a leading cause of acute respiratory illness, with severe outcomes in older adults. Information on the prevalence, hospitalization rate, and impact on the health-related quality of life (HRQoL) of RSV in older adults with acute respiratory infections (ARI) in outpatient settings in Japan is limited. MethodsThis multi-center epidemiological study included outpatients aged ≥60 years presenting with ARI between August 2021 and February 2023. Nasal and throat swabs were collected and tested by reverse transcription polymerase chain reaction (RT-PCR). The prevalence of RT-PCR-confirmed RSV (cRSV)-ARI, cRSV-lower respiratory tract disease (LRTD), and other respiratory viruses was calculated by season, region, age group, and RSV subtype. HRQoL was assessed via patient-reported outcomes. ResultsThe study included 923 ARI episodes (cRSV-ARI: N = 24; non-cRSV-ARI: N = 899). In years 1 and 2 (August 2021–July 2022 and August 2022–February 2023), the prevalence of cRSV-ARI was 2.5% and 2.8%, respectively. There was a predominance of RSV-B and RSV-A subtypes in years 1 and 2, respectively. In years 1 and 2 combined, 37.5% of cRSV-ARI cases had lower respiratory tract infection; all cRSV-LRTD cases occurred in those aged 60–74 years. RSV-ARI cases reported throat, chest, and respiratory symptoms, leading to impaired functioning and HRQoL. ConclusionsDuring the observed study period, RSV was circulating among older adults in Japan. RSV was a leading cause of ARI and LRTD. More data are needed to fully clarify the burden of RSV among older adults in Japan.

РОЛЬ ИММУННОГО ОТВЕТА В РАЗВИТИИ ГИПОКСИЧЕСКИХ ОСЛОЖНЕНИЙ РЕСПИРАТОРНЫХ ИНФЕКЦИЙ НИЖНИХ ДЫХАТЕЛЬНЫХ ПУТЕЙ У ДЕТЕЙ

Pneumonia is one of the most common severe infectious diseases in pediatric practice. Hypoxia is common in children with pneumonia and is one of the main predictors of poor outcome. The role of the central link in the cellular response to hypoxia is played by the family of hypoxia-inducible factors (HIF). HIF-1α is the key regulator of both T- and B-lymphocyte functions. The processes of their maturation are accompanied by the formation of circular DNA fragments, TREC (T-cell Receptor Excision Circle) and KREC (Kappa-deleting Recombination Excision Circle). TREC and KREC are unable to replicate and serve as markers for naive lymphocyte production. In its turn, HIF-1α can be used as a marker for cellular hypoxia. The use of TREC and KREC in assessing the immune system in patients with various immunological and infectious pathologies has already been described. At the same time, HIF-1α has so far been little studied as yet. The purpose of this research was to analyze the scientific bibliographical data on the HIF-1α assessment as a marker for hypoxia as well as the quantitative level of TREC and KREC as markers for the adaptive immune response; to study the bibliographical sources on the effect of hypoxia on the immune response, including as part of lower respiratory tract infections. Methods used: bibliographical research in Scopus, PubMed and Google Scholar with keywords “TREC,” “KREC,” “HIF,” “hypoxia,” “pneumonia,” “immune response,” that was then followed by the search results’ systematization, analysis and synthesis. Results: the analysis of bibliographical sources had allowed the Authors to conclude that there is a possible close connection between acute hypoxia and the formation of an adequate immune response in infectious pathologies. Research in this area is still extremely scarce. At the same time, the prospects for this area determine the need for further fundamental and clinical research. Conclusion: it is of a great scientific and clinical interest to be able to non-invasively assess the degree of acute hypoxia during an ongoing infectious disease by examining urinary HIF-1α levels. Particularly promising is the assessment of the HIF-1α level not only as a regulator of tissue adaptation to acute hypoxia, but also as a modulator of the immune response. Taking into consideration the analyzed data, both TREC and KREC appear to be the optimal markers characterizing the functional state of the adaptive immune system.

TAS2R38 Genotype Does Not Affect SARS-CoV-2 Infection in Primary Ciliary Dyskinesia.

Several chronic respiratory diseases could be risk factors for acquiring SARS-CoV-2 infection: among them, Primary Ciliary Dyskinesia (PCD) is a rare (about 1:10.000) inherited ciliopathy (MIM 242650) characterized by recurrent upper and lower respiratory tract infections due to a dysfunction of the respiratory cilia. In this study, we aimed to investigate whether PCD subjects are more susceptible to infection by SARS-CoV-2 and whether some polymorphisms of the TAS2R38 bitter taste receptor correlate with an increased prevalence of SARS-CoV-2 infection and severity of symptoms. Patients answered several questions about possible SARS-CoV-2 infection, experienced symptoms, and vaccinations; in the case of infection, they also filled out a SNOT-22 questionnaire and ARTIQ. Forty PCD adult patients (mean age, 36.6 ± 16.7 years; 23 females, 17 males) participated in this study, out of which 30% had tested positive for COVID-19 during the last four years; most of them reported a mildly symptomatic disease. We found no differences in age or sex, but a statistically significant difference (p = 0.03) was observed in body mass index (BMI), which was higher in the COVID-acquired group (23.2 ± 3.3 vs. 20.1 ± 4.1 kg/m2). Genotyping for TAS2R38 polymorphisms showed a prevalence of 28.6% PAV/PAV, 48.6% PAV/AVI, and 22.8% AVI/AVI individuals in our cohort. In contrast to our hypothesis, we did not observe a protective role of the PAV allele towards SARS-CoV-2 infection. Conclusions: Our findings suggest that subjects with PCD may not be at increased risk of severe outcomes from COVID-19 and the TAS2R38 bitter taste receptor genotype does not affect SARS-CoV-2 infection.

A self-amplifying RNA vaccine prevents enterovirus D68 infection and disease in preclinical models.

The recent emergence and rapid response to severe acute respiratory syndrome coronavirus 2 was enabled by prototype pathogen and vaccine platform approaches, driven by the preemptive application of RNA vaccine technology to the related Middle East respiratory syndrome coronavirus. Recently, the National Institutes of Allergy and Infectious Diseases identified nine virus families of concern, eight enveloped virus families and one nonenveloped virus family, for which vaccine generation is a priority. Although RNA vaccines have been described for a variety of enveloped viruses, a roadmap for their use against nonenveloped viruses is lacking. Enterovirus D68 was recently designated a prototype pathogen within the family Picornaviridae of nonenveloped viruses because of its rapid evolution and respiratory route of transmission, coupled with a lack of diverse anti-enterovirus vaccine approaches in development. Here, we describe a proof-of-concept approach using a clinical stage RNA vaccine platform that induced robust enterovirus D68-neutralizing antibody responses in mice and nonhuman primates and prevented upper and lower respiratory tract infections and neurological disease in mice. In addition, we used our platform to rapidly characterize the antigenic diversity within the six genotypes of enterovirus D68, providing the necessary data to inform multivalent vaccine compositions that can elicit optimal breadth of neutralizing responses. These results demonstrate that RNA vaccines can be used as tools in our pandemic-preparedness toolbox for nonenveloped viruses.

Diagnostic Challenges in Depression – A Rare Case of Depression Associated with Pachymeningitis

Abstract Hypertrophic pachymeningitis is a rare neurological disorder, with nonspecific initial symptoms, which lead to difficulty in early diagnosis. Psychiatric manifestations have rarely been reported in association with this disorder. In this article, we report the case of a female patient, who was initially diagnosed as suffering from depressive disorder but was later diagnosed as suffering from underlying hypertrophic pachymeningitis. The bidirectional nature of depression with inflammation can also be ascertained from the course of the disease and the treatment offered. The initial presenting depressive symptoms, somatic complaints, headache, and ocular symptoms had responded well to paroxetine, until there was an episode of lower respiratory tract infection, following which all her symptoms aggravated. Detailed neurological work-up confirmed the diagnosis of pachymeningitis. Immunosuppressant therapy was employed using steroids, while continuing paroxetine, which led to near-complete recovery of both her ocular and depressive symptoms.

Supporting vaccine (co)-administration decisions: Development and validation of a tool for assessing the risk of severe outcomes due to lower respiratory tract infections

ObjectiveTo develop and validate a score to predict the 90-day risk of hospitalization/death in patients with low respiratory tract infections (LRTIs) with the aim to support clinical decision making on vaccine (co)-administration. MethodsWe formed a cohort of patients aged 18 years or older being diagnosed with LRTIs in the period between January 1, 2012 and December 31, 2022. Each patient was followed until occurrence of respiratory-related hospitalization/death up to the end of the study period (December 31, 2022). Along with age and sex, forty determinants were adopted to assemble the respiratory tract infection (RTI)-Health Search (HS) core using the development sub-cohort. The prediction accuracy of the score was therefore assessed in the validation sub-cohort. ResultsWe identified 252,319 patients being diagnosed with LRTIs (females: 54.7 %; mean age: 60 (SD:18.1)). When the risk of LRTIs-related hospitalizations/deaths was estimated via RTI-HScore, its predicted value was equal to 1.4 % over a 90-day event horizon. The score showed explained variation and discrimination accuracy were equal to 45 % (95 % CI: 44–47 %) and 81 % (95 % CI: 79–84 %), respectively. The calibration slope did not significantly differ from the unit (p = 0.8314). ConclusionsThe RTI-HScore was featured by good accuracy for prediction of LRTIs-related complications over a 90-day follow-up. Such a tool might therefore support general practitioners to enhance patients’ care by facilitating approaches for (co)-administration of vaccines for respiratory infections through a score-based decision support system.

Economic burden of respiratory syncytial virus in adults in Germany – a health claims analysis between 2015 and 2018

Aims Respiratory syncytial virus (RSV) causes severe lower respiratory tract infections (LRTI) in infants and adults. While the clinical burden was recently estimated in adults in Germany, little is known about the economic burden. To fill this gap, this study aimed to assess hospital and outpatient healthcare resource utilization (HRU) and costs of RSV infections in adults in Germany. Methods In this retrospective, observational study on nationwide, representative, anonymized claims data (2015–2018), we identified patients ≥18 years with ICD-10-GM-codes specific to RSV (“RSV-specific”). To increase sensitivity, patients with unspecified LRTIs (including unspecified bronchitis, bronchiolitis, bronchopneumonia, and pneumonia) during RSV seasons were also included as cases potentially caused by RSV (“RSV-possible”). RSV-related HRU (hospital days, ICU and ventilation treatment, drug dispensation) and direct costs were estimated per episode. Excess costs per episode and for follow-up periods were compared to a matched control cohort. All outcomes were reported per healthcare sector and stratified by age and risk groups as well as disease severity (ICU admission/ventilation). Results Direct inpatient and outpatient mean episode costs were 3,473€ and 82€, respectively, with substantially higher costs for severe cases requiring intensive care and/or ventilation (10,801€). Direct costs for RSV-specific cases were higher than for RSV-possible cases (inpatients: 6,247€ vs. 3,450€; outpatients: 127€ vs. 82€). Moreover, costs were significantly higher for RSV patients than for controls and increased over time (inpatients: 5,140€ per episode vs 10,093€ per year; outpatients: 46€ per quarter vs 114€ per year). Limitations While the number of RSV-specific cases was low, inclusion of seasonal LRTI cases likely increased the sensitivity to detect RSV cases and allowed a better estimation of the total costs of RSV. Conclusions The economic burden of RSV-LRTI in adults in Germany is substantial, persists long-term, and is particularly high in the elderly. This highlights the need for cost-effective prevention measures.

Nursing Implementation of Ineffective Breathing Patterns in Toddlers with Acute Respiratory Infection: A Case Study

Acute Respiratory Infection is an upper and lower respiratory tract infection that attacks the throat, nose and lungs at mild to severe levels lasting approximately 14 days. This study uses a case study method in the form of a description of the nursing care process in patients in accordance with the theory and contains a discussion of nursing actions that occur in the field. This study was conducted for 3 days with a total of 3 visits to patients starting from 15-17 May 2023, data obtained from interviews, observations, physical examinations. This study uses the concept of nursing care starting from assessment, appointment of nursing diagnoses, provision of nursing interventions, nursing implementation and nursing evaluation carried out for 3 days. the instrument used is the surgical medical nursing care assessment format. The results obtained by Baby D that he was less congested after being given nebulizer therapy, pulse: 160x/min, Temperature: 36.70C, respiration rate: 55x/min, Spo2: 99%, baby D still looks a little tight, using a breathing apparatus (nasal cannula), the client's general condition has improved slightly. It is expected that clients and families maintain and improve health by implementing a healthy lifestyle and utilizing existing health facilities for health control to accelerate recovery, so that the problem of Ineffective Breathing Patterns in clients with Acute Respiratory Tract Infection can be resolved.

Safety, Tolerability, and Pharmacokinetics of Nebulized GB05-Human IFNα1b Inhalation Solution: A Randomized, Placebo-Controlled, Dose-Escalation PhaseI Study in Healthy Chinese Adult Volunteers.

Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection, especially in children and older people. However, no effective treatment is currently available. TypeI interferons (IFNs) are a group of cytokines that help regulate the activity of the immune system. GB05, human IFNα1b inhalation solution, was developed under US Food and Drug Administration (FDA) standard guidelines to combat RSV infection. This randomized, double-blind, placebo-controlled, dose-escalation phaseI trial evaluated the safety, tolerability, and pharmacokinetics of nebulized GB05. A total of 35 eligible healthy Chinese adult volunteers were enrolled in this study. In the single ascending dose (SAD) study, volunteers were randomized into 0.2, 0.6, 1.2, and 1.8million IU of GB05 or placebo. In the multiple ascending dose (MAD) study, volunteers received 1.2 or 1.8million IU of GB05 or placebo for four consecutive days. Safety, tolerability, immunogenicity, and plasma pharmacokinetics were assessed for all groups. All adverse events were mild or moderate and resolved spontaneously. The most common adverse event was decreased white blood cell count (8.6% in SAD and 10% in MAD). No serious adverse events, deaths, or adverse events that reached the termination criteria occurred during the study. In SAD, the maximum concentration and area under the curve increased across the dose range of 1.2-1.8million IU in a non-linear relationship. The maximum plasma concentration after GB05 nebulization (1.06IU/ml in the 1.8million IU group) reflected a low concentration in the blood, suggesting a better lung uptake of GB05 and reduced incidence or risks of adverse events. In MAD, a steady state was reached after continuous administrations of twice daily for 3days. Overall, nebulized GB05 exhibited satisfactory safety, tolerability, and favorable pharmacokinetic (PK) profiles in healthy adult volunteers, supporting further clinical investigation in patients infected with respiratory syncytial virus. ClinicalTrials.gov Identifier NCT06277167.

Ronald Ferguson Ingle (1927 - 2022).

Respiratory syncytial virus (RSV) is the commonest cause of lower respiratory tract infection (LRTI) in children, particularly those aged <1 year. In South Africa (SA), increased hospitalisation rates during the RSV season, including access to intensive care facilities, place a huge burden on the healthcare system. Furthermore, RSV-LRTI during early childhood may lead to long-term respiratory sequelae, including recurrent wheezing, asthma, and impairment of lung function. Recently, two new RSV prevention strategies have emerged: nirsevimab, a long-acting monoclonal antibody, and a maternal RSV vaccine. Both strategies have shown high efficacy in reducing RSV-LRTI hospitalisation in infants and are being considered for licensure in SA. Implementation of these prevention strategies, combined with public engagement and collaboration between stakeholders, could significantly reduce RSV-related morbidity and mortality in SA.

Phenotypic and molecular characterization of Streptococcus pneumoniae serotype 3 isolates from blood and respiratory samples in Canada: CANWARD 2007-21.

Lower respiratory infections and invasive disease caused by Streptococcus pneumoniae serotype 3 remain major clinical challenges around the world, despite widespread availability of updated vaccines. As part of CANWARD, antimicrobial susceptibility testing and serotyping were performed on all S. pneumoniae isolates from 2007 to 2021. A subset of 226/264 (85.6%) serotype 3 isolates were selected for WGS to determine sequence type (ST)/clonal cluster (CC) and correspondence of antimicrobial resistance determinants (erm, mefAE, tetM, cat, folA, folP) with resistance phenotype. Of the 3,039 S. pneumoniae isolates obtained from 2007 to 2021, 8.7% (n = 264) were serotype 3, with 64.0% of respiratory origin and 36.0% from blood. Of 226 sequenced serotype 3 isolates, 184 (81.4%) were ST180 (GPSC12). The proportion of ST8561 (single locus variant of ST180) increased from 7.2% to 16.6% during the study period. An increasing proportion of serotype 3 isolates had phenotypic resistance (P = 0.0007) and genetic resistance determinants (P = 0.004), comparing 2017-21 to 2007-11, largely due to a recently expanded ST180 clade with cat, tetM and mef determinants. S. pneumoniae serotype 3 from GPSC12 continues to dominate throughout Canada, with an increase in the proportion of ST8561. The proportion of serotype 3 isolates that are phenotypically resistant and with genetic resistance determinants is increasing over time, reflecting a global increase in GPSC12 genotypes with known resistance determinants. Phylogenomic characterization of isolates collected over time and from around the world may facilitate improved treatment and enhanced prevention strategies, including new vaccines with activity against S. pneumoniae serotype 3.

Primary ciliary dyskinesia: Meeting the challenges of diagnosis in South Africa.

Primary ciliary dyskinesia (PCD) is an inherited ciliopathy that results in impaired mucous clearance and affects primarily the respiratory tract, causing upper airway disease, bronchial inflammation and bronchiectasis. The prevalence of PCD in low- and middle-income settings, including South Africa (SA), is unknown, largely owing to challenges with diagnosis, and identifying children or adults with PCD is challenging in a setting with a high prevalence of other infectious diseases, including lower respiratory tract infections and tuberculosis. No single test is diagnostic of PCD, and while some tests are costly, others are labour intensive and require highly specialised laboratory expertise. In the SA setting, awareness and opportunities for the diagnosis of PCD need to be created. In this commentary, we provide a pragmatic approach to identifying which children and adults require further investigations for PCD using a range of diagnostic tests or tools that are available. Furthermore, we recommend that designated centres of expertise for PCD diagnosis are created in SA. This would be an important step towards improving accessibility of diagnostic tests and developing local expertise to improving PCD diagnosis, especially in early childhood, to prevent long-term irreversible respiratory sequelae.

Efficacy, Safety, and Immunogenicity of Subunit Respiratory Syncytial Virus Vaccines: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Respiratory syncytial virus (RSV) is garnering increasing attention, with a growing number of subunit RSV vaccines under active clinical investigation. However, comprehensive evidence is limited. We conducted a comprehensive search across PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov from database inception to 12 January 2024, focusing on published randomized controlled trials (RCTs). A total of 17 studies were included, encompassing assessments of efficacy (5 studies), safety (17 studies), and immunogenicity (12 studies) of RSV subunit vaccines. The pooled risk ratio (RR) for RSV-associated acute respiratory infection (RSV-ARI) with subunit vaccines was 0.31 (95% CI: 0.23-0.43), for RSV-associated lower respiratory tract infection (RSV-LRTI), it was 0.32 (95% CI: 0.22-0.44), and for severe RSV-LRTI (RSV-SLRTI), it was 0.13 (95% CI: 0.06-0.29). There was no significant difference in serious adverse events (SAEs) between the vaccine and placebo groups, with a pooled RR of 1.05 (95% CI: 0.98-1.14). The pooled standardized mean difference (SMD) for the geometric mean titer (GMT) of neutralizing antibodies was 2.89 (95% CI: 2.43-3.35). Subunit RSV vaccines exhibit strong efficacy, favorable safety profiles, and robust immunogenicity. Future research should focus on the cost-effectiveness of various vaccines to enhance regional and national immunization strategies.

Global epidemiological trends in the incidence and deaths of acute respiratory infections from 1990 to 2021

The aim of this study was to investigate the global epidemiological trends in the incidence and deaths of acute respiratory infections (ARIs), encompassing both upper respiratory infections (URIs) and lower respiratory infections (LRIs), from 1990 to 2021. Using data from the Global Burden of Disease study 2021 (GBD 2021), we utilized the average annual percentage change (AAPC) to examine the trends in the age-standardized incidence rate and deaths rate (ASIR and ASDRs) of URIs and LRIs. In 2021, the global ASIR of URIs and LRIs were 166,770.73 (95 % UI: 148,098.16–189,487.93) per 100,000 and 4283.61 (95 % UI: 4057.03–4524.89) per 100,000, respectively. The highest ASIR of URIs occurred in high-sociodemographic index (SDI) regions (232744.64, 95 % UI: 206887.07–261694.81) per 100,000, whereas LRIs occurred in low-SDI regions (9261.1, 95 % UI: 8741.61–9820.86) per 100,000. In 2021, the global ASDRs of URIs and LRIs were 0.28 (95 % UI: 0.09–0.61) per 100,000 and 28.67 (95 % UI: 25.92–31.07) per 100,000, respectively. The highest ASDRs of both URIs and LRIs were observed in low-SDI regions, with 1.1 (95 % UI: 0.08–2.78) per 100,000 and 70.68 (95 % UI: 62.56–78.62) per 100,000, respectively. From 1990 to 2021, the global ASIR for URIs and LRIs decreased, with AAPCs of −0.17 % (95 % CI: −0.17 % to −0.16 %) and −1.28 % (95 % CI: −1.37 % to −1.22 %), respectively. The global ASDRs also decreased (−3.39 % for URIs; −2.46 % for LRIs). However, during the COVID-19 pandemic, the ASIR of URIs increased in many countries, especially in high-SDI regions (rate difference before and during the COVID-19 pandemic in ASIR was 2210.19 per 100,000.) and low-SDI regions (rate difference in ASIR: 111.26 per 100,000). The global incidence and deaths related to ARIs have decreased over the past 32 years. However, it remains a significant public health concern, particularly due to the notable incidence of URIs in high SDI regions and the deaths associated with both URIs and LRIs in low SDI regions. Furthermore, an increase in the incidence of URIs was observed in both high- and low-SDI regions during the COVID-19 pandemic, highlighting the need for increased attention.

Application of Second-Generation Sequencing Technology in Lower Respiratory Tract Infection.

Lower respiratory tract infection (LRTI) has long been an important threat to people's life and health, so the rapid diagnosis of LRTI is of great significance in clinical treatment. In recent years, the development of the sequencing technology provides a new direction for the rapid diagnosis of LRTI. In this review, the advantages and disadvantages of second-generation sequencing techniques represented by metagenomics next-generation sequencing (mNGS) and droplet digital polymerase chain reaction (ddPCR) in LRTI were reviewed. Furthermore, it offers insights into the future trajectory of this technology, highlighting its potential to revolutionise the field of respiratory infection diagnostics. This review summarises developments in mechanistic research of second-generation sequencing technology their relationship with clinical practice, providing insights for future research. Authors conducted a search on PubMed and Web of Science using the professional terms 'Lower respiratory tract infection' and 'droplet digital polymerase chain reaction' and 'metagenomics next generation sequencing'. The obtained literature was then roughly categorised based on their research content. Similar studies were grouped into the same sections, and further searches were conducted based on the keywords of each section. Different studies discussed the application of second-generation sequencing technology in LRTI from different angles, including the detection of pathogens of LRTI by mNGS and ddPCR, the prediction ability of drug-resistant bacteria, and comparison with traditional methods. We try to analyse the advantages and disadvantages of the second-generation sequencing technology by combing the research results of mNGS and ddPCR. In addition, the development direction of the second-generation sequencing technology is prospected.

Sarcoidosis and Emergency Hospitalization

IntroductionSarcoidosis is an idiopathic systemic granulomatosis whose evolution is self-limiting in the majority of cases. However, it can progress to organ damage that menaces the vital or functional prognosis of patients. Sarcoidosis itself, but also its comorbidities, can pose a threat to the patient, require rapid initiation of treatment and justify emergency hospitalization. Research questionWhat are the reasons and prognosis of sarcoidosis patients hospitalized in emergency ? MethodsThe objectives of our study were to describe the causes of admission, and to identify predictors of mortality in sarcoidosis patients hospitalized in emergency. This is a retrospective monocentric study. We included patients hospitalized after a stay in the emergency room or in intensive care unit (ICU) or requiring an unscheduled hospitalization after a telephone advice or a consultation, between 01/01/2017 and 07/07/2020. ResultsWe identified 154 sarcoidosis patients hospitalized in emergency, among which 14 (9%) required the ICU. There were 81 men, with a median age of 55.0 [44.0; 67.0] years. Sarcoidosis was inaugural in 20 (14%) patients. The primary reason for hospitalization was lower respiratory infections in 32 (21%) patients, followed by acute pulmonary exacerbation of sarcoidosis in 17 (11%), suspected cardiac sarcoidosis in 13 (8.4%), and neurosarcoidosis in 12 (7.7%). The median length of stay was 6 [3.00; 10.0] days. In-hospital mortality rate was 3.9%. The 2-year transplantation-free survival following hospitalization was 86,8% [95% CI 81,4- 92,5]. The factors associated with a worse transplantation-free survival were Charlson comorbidity index (HR=1.29 [95% CI=1.04-1.61]; p=0.021), pulmonary hypertension (HR=2.53 [95% CI=1.10-5.83]; p=0.029), and oxygen therapy during hospitalization (HR=4.18 [95%CI=1.55-11.29]; p=0.005). InterpretationThe overall mortality of sarcoidosis patients hospitalized in emergency is high. The presence of comorbidities and the severity of respiratory failure, as reflected by oxygen requirement, are important prognostic determinants.

Non-COVID Respiratory Infections Related Emergency Room Visits Among Autistic Adults in the United States

IntroductionThis is a retrospective study to examine the risk of non-COVID-19 respiratory infection (RI) related emergency department (ED) visits and hospitalizations among autistic adults compared to non-autistic adults using the 2018 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample (HCUP-NEDS). MethodsThe data were analyzed in 2022 using the ICD-10-CM codes to extract about 46,996 autistic case records that were matched by age and sex with non-autistic records (140,997) in a 1:3 case-control ratio. Respiratory infections were also identified using the ICD-10-CM codes and classified by type. Logistic regression models were conducted for the likelihood of presenting with RI infections to the ED and subsequent hospitalization. All models were adjusted for covariates. ResultsAutistics were more likely to present with any type of respiratory infection at the emergency department (AOR = 1.83: CI= 1.69-2.42), lower respiratory infections (AOR=1.37: CI=1.09-1.50), and pneumonia (AOR=2.42: CI=1.98-2.47) compared to non-autistics. They are also more likely to be hospitalized from RIs during ED visits (AOR=3.87: CI=3.21-4.30), including upper and lower RIs, pneumonia, and bronchitis. ConclusionsAutistic individuals were more likely to experience emergency department visits and hospitalizations due to respiratory infections compared to non-autistic individuals. Amid growing evidence of the disproportionate impact of COVID-19 on the autistic population, our findings highlight a broader, pre-existing burden of respiratory infections among autistic adults in the US that extends beyond the recent pandemic.