Pathogenic features and clinical characteristics of acute community-acquired lower respiratory tract infections.

Objective: To investigate the pathogen distribution and clinical characteristics of acute community-acquired lower respiratory tract infections (CALRTIs). Methods: This was a retrospective study. The clinical data of 218 patients with CALRTIs admitted to Baoding No.1 Central Hospital from December 2021 to December 2022 were retrospectively collected and were divided into two groups according to the results of polymerase chain reaction(PCR) testing using a nasopharyngeal swab: streptococcus pneumoniae positive group(observation group) and non-streptococcus pneumoniae positive group(control group). Clinical symptoms, blood gas analysis indicators were compared between the two groups. Results: Haemophilus influenzae and Staphylococcus aureus, as well as virus and atypical pathogen infection, were the predominant pathogenic bacteria in both groups. No statistically significant differences were observed in the positive rates of sputum smear, sputum culture, respiratory virus detection and atypical pathogen detection between the two groups(P>0.05). However, the control group had a higher detection rate of gram-positive bacteria, gram-negative bacteria and Legionella pneumophila in sputum smears than the observation group, with a statistically significant difference(P<0.05). One death occurred in each group, with no significant difference in mortality and six in each group left the hospital or were transferred due to deterioration, with no significant difference in improved discharge rates. Conclusion: Acute community-acquired lower respiratory tract infections(CALRTIs) take bacteria, viruses and atypical pathogens as its leading pathogenic bacteria. In the treatment of patients with acute CALRTIs, early pathogenic examination should be performed to assist in guiding antibiotic therapy for rapid control, early recovery and ameliorated clinical outcomes.

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 yet. To fill this gap, we 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 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.

Impact of C-reactive protein point-of-care testing on antibiotic prescriptions for children and adults with suspected respiratory tract infections in primary care: a French patient-level randomized controlled superiority trial.

OBJECTIVES: The value of C-reactive protein point-of-care testing (CRP POCT) to guide antibiotic prescriptions in adults has previously been emphasized. The aim of this study was to assess the impact of CRP POCT on antibiotic prescriptions by general practitioners (GPs) for suspected lower respiratory tract infections in children ≥3 years old and in adults. METHODS: This was an open-label randomized trial (NCT03540706) conducted in 26 GPs in France between October 2019 and March 2023. Of the 404 participating patients, 207 (51.2%) were randomized to the CRP POCT group and 197 (48.8%) to the control group (i.e. no CRP POCT). During consultations, GPs measured CRP levels in patients randomized to the CRP POCT group. The primary endpoint was the proportion of patients in each group who were prescribed antibiotics by their GP during the consultation. Z-tests were used for comparisons. RESULTS: The overall proportion of patients treated with antibiotics was similar in the CRP POCT (n = 89/207, 43% CI: 36.2, 50.0) and in the control group (n = 94/197, 47.7% CI: 40.6, 54.9), difference: -4.7 CI: -14.4, 5.0; p 0.3. Overall, 75% of the GPs followed CRP-based antibiotic prescription recommendations in the CRP POCT group. DISCUSSION: CRP POCT did not reduce antibiotic prescriptions in this trial.

Economic burden of respiratory syncytial virus disease in Latin America: A systematic review.

This Systematic Review assesses the economic impact of Respiratory Syncytial Virus (RSV) in Latin America and the Caribbean (LAC) in relation to healthcare resource utilization and associated costs. We searched online databases from January 2012 to November 2022 to identify eligible publications. We identified 12 publications that reported direct costs, indirect costs, and resources associated with RSV and its complications. The primary direct medical resources reported were medical services, diagnostics tests and procedures, and length of stay (LOS). Direct total costs per patient ranged widely from $563 to $19,076. Direct costs are, on average, 98% higher than indirect costs. Brazil reported a higher total cost per patient than Colombia, El Salvador, México, Panamá, and Puerto Rico, while for indirect costs per patient, El Salvador and Panamá had higher costs than Brazil, Colombia, and Mexico. The mean LOS in the general ward due to RSV was 6.9 days (range 4 to 20 days) and the mean Intensive Care Unit LOS was 9.1 days (range 4 to 16 days). In many countries of the LAC region, RSV represents a considerable economic burden on health systems, but significant evidence gaps were identified in the region. More rigorous health economic studies are essential to better understand this burden and to promote effective healthcare through an informed decision-making process. Vaccination against RSV plays a critical role in mitigating this burden and should be a priority in public health strategies.

Impact of lower-respiratory tract infections on healthcare utilization and mortality in older adults: a Swedish population-based cohort study.

BACKGROUND: Lower respiratory tract infections (LRTIs) have an immediate significant impact on morbidity and mortality among older adults. However, the impact following the infectious period of LRTI remains understudied. We aimed to assess the short- to long-term impact of LRTIs on hospitalization, mortality, and healthcare utilization in older adults. METHODS: Data from the Swedish National Study of Aging and Care in Kungsholmen (SNAC-K) was analyzed, with data from 2001 to 2019 for mortality and 2001-2016 for healthcare utilization. LRTI-exposed participants were identified and matched with LRTI-nonexposed based on sociodemographics, lifestyle factors, and functional and clinical characteristics. Statistical models evaluated post-LRTI hospitalization risk, days of inpatient hospital admissions, healthcare visits, and mortality. RESULTS: 567 LRTIs-exposed participants during the study period and were matched with 1.701 unexposed individuals. LRTI-exposed individuals exhibited increased risk of hospitalization at 1-year (HR 2.14, CI 1.74, 2.63), 3-years (HR 1.74, CI 1.46, 2.07), and 5-years (HR 1.59, CI 1.33, 1.89). They also experienced longer post-LRTI hospital stays (IRR 1.40, CI 1.18, 1.66), more healthcare visits (IRR 1.47, CI 1.26, 1.71), specialist-care visits (IRR 1.46, CI 1.24, 1.73), and hospital admissions (IRR 1.57, CI 1.34, 1.83) compared to nonexposed participants over 16-years of potential follow-up. Additionally, the 19-year risk of mortality was higher among LRTI-exposed participants (HR 1.45, CI 1.24, 1.70). Men exhibited stronger associations with these risks compared to women. CONCLUSIONS: LRTIs pose both short- and long-term risks for older adults, including increased risks of mortality, hospitalization, and healthcare visits that transpire beyond the acute infection period, although these effects diminish over time. Men exhibit higher risks across these outcomes compared to women. Given the potential preventability of LRTIs, further public health measures to mitigate infection risk are warranted.

Model-based disease mapping using primary care registry data.

BACKGROUND: Spatial modeling of disease risk using primary care registry data is promising for public health surveillance. However, it remains unclear to which extent challenges such as spatially disproportionate sampling and practice-specific reporting variation affect statistical inference. METHODS: Using lower respiratory tract infection data from the INTEGO registry, modeled with a logistic model incorporating patient characteristics, a spatially structured random effect at municipality level, and an unstructured random effect at practice level, we conducted a case and simulation study to assess the impact of these challenges on spatial trend estimation. RESULTS: Even with spatial imbalance and practice-specific reporting variation, the model performed well. Performance improved with increasing spatial sample balance and decreasing practice-specific variation. CONCLUSION: Our findings indicate that, with correction for reporting efforts, primary care registries are valuable for spatial trend estimation. The diversity of patient locations within practice populations plays an important role.

A single-center, retrospective study of hospitalized patients with lower respiratory tract infections: clinical assessment of metagenomic next-generation sequencing and identification of risk factors in patients.

INTRODUCTION: Lower respiratory tract infections(LRTIs) in adults are complicated by diverse pathogens that challenge traditional detection methods, which are often slow and insensitive. Metagenomic next-generation sequencing (mNGS) offers a comprehensive, high-throughput, and unbiased approach to pathogen identification. This retrospective study evaluates the diagnostic efficacy of mNGS compared to conventional microbiological testing (CMT) in LRTIs, aiming to enhance detection accuracy and enable early clinical prediction. METHODS: In our retrospective single-center analysis, 451 patients with suspected LRTIs underwent mNGS testing from July 2020 to July 2023. We assessed the pathogen spectrum and compared the diagnostic efficacy of mNGS to CMT, with clinical comprehensive diagnosis serving as the reference standard. The study analyzed mNGS performance in lung tissue biopsies and bronchoalveolar lavage fluid (BALF) from cases suspected of lung infection. Patients were stratified into two groups based on clinical outcomes (improvement or mortality), and we compared clinical data and conventional laboratory indices between groups. A predictive model and nomogram for the prognosis of LRTIs were constructed using univariate followed by multivariate logistic regression, with model predictive accuracy evaluated by the area under the ROC curve (AUC). RESULTS: (1) Comparative Analysis of mNGS versus CMT: In a comprehensive analysis of 510 specimens, where 59 cases were concurrently collected from lung tissue biopsies and BALF, the study highlights the diagnostic superiority of mNGS over CMT. Specifically, mNGS demonstrated significantly higher sensitivity and specificity in BALF samples (82.86% vs. 44.42% and 52.00% vs. 21.05%, respectively, p < 0.001) alongside greater positive and negative predictive values (96.71% vs. 79.55% and 15.12% vs. 5.19%, respectively, p < 0.01). Additionally, when comparing simultaneous testing of lung tissue biopsies and BALF, mNGS showed enhanced sensitivity in BALF (84.21% vs. 57.41%), whereas lung tissues offered higher specificity (80.00% vs. 50.00%). (2) Analysis of Infectious Species in Patients from This Study: The study also notes a concerning incidence of lung abscesses and identifies Epstein-Barr virus (EBV), Fusobacterium nucleatum, Mycoplasma pneumoniae, Chlamydia psittaci, and Haemophilus influenzae as the most common pathogens, with Klebsiella pneumoniae emerging as the predominant bacterial culprit. Among herpes viruses, EBV and herpes virus 7 (HHV-7) were most frequently detected, with HHV-7 more prevalent in immunocompromised individuals. (3) Risk Factors for Adverse Prognosis and a Mortality Risk Prediction Model in Patients with LRTIs: We identified key risk factors for poor prognosis in lower respiratory tract infection patients, with significant findings including delayed time to mNGS testing, low lymphocyte percentage, presence of chronic lung disease, multiple comorbidities, false-negative CMT results, and positive herpesvirus affecting patient outcomes. We also developed a nomogram model with good consistency and high accuracy (AUC of 0.825) for predicting mortality risk in these patients, offering a valuable clinical tool for assessing prognosis. CONCLUSION: The study underscores mNGS as a superior tool for lower respiratory tract infection diagnosis, exhibiting higher sensitivity and specificity than traditional methods.

Characteristics of children readmitted with severe pneumonia in Kenyan hospitals.

BACKGROUND: Pneumonia is a leading cause of childhood morbidity and mortality. Hospital re-admission may signify missed opportunities for care or undiagnosed comorbidities. METHODS: We conducted a retrospective cohort study including children aged ≥ 2 months-14 years hospitalised with severe pneumonia between 2013 and 2021 in a network of 20 primary referral hospitals in Kenya. Severe pneumonia was defined using the 2013 World Health Organization criteria, and re-admission was based on clinical documentation from individual patient case notes. We estimated the prevalence of re-admission, described clinical management practices, and modelled risk factors for re-admission and inpatient mortality. RESULTS: Among 20,603 children diagnosed with severe pneumonia, 2,274 (11.0%, 95% CI 10.6-11.5) were readmitted. Re-admission was independently associated with age (12-59 months vs. 2-11 months: adjusted odds ratio (aOR) 1.70, 1.54-1.87; >5 years vs. 2-11 months: aOR 1.85, 1.55-2.22), malnutrition (weight-for-age-z-score (WAZ) <-3SD vs. WAZ> -2SD: aOR 2.05, 1.84-2.29); WAZ - 2 to -3 SD vs. WAZ> -2SD: aOR 1.37, 1.20-1.57), wheeze (aOR 1.17, 1.03-1.33) and presence of a concurrent neurological disorder (aOR 4.42, 1.70-11.48). Chest radiography was ordered more frequently among those readmitted (540/2,274 [23.7%] vs. 3,102/18,329 [16.9%], p < 0.001). Readmitted patients more frequently received second-line antibiotics (808/2,256 [35.8%] vs. 5,538/18,173 [30.5%], p < 0.001), TB medication (69/2,256 [3.1%] vs. 298/18,173 [1.6%], p < 0.001), salbutamol (530/2,256 [23.5%] vs. 3,707/18,173 [20.4%], p = 0.003), and prednisolone (157/2,256 [7.0%] vs. 764/18,173 [4.2%], p < 0.001). Inpatient mortality was 2,354/18,329 (12.8%) among children admitted with a first episode of severe pneumonia and 269/2,274 (11.8%) among those who were readmitted (adjusted hazard ratio (aHR) 0.93, 95% CI 0.82-1.07). Age (12-59 months vs. 2-11 months: aHR 0.62, 0.57-0.67), male sex (aHR 0.81, 0.75-0.88), malnutrition (WAZ <-3SD vs. WAZ >-2SD: aHR 1.87, 1.71-2.05); WAZ - 2 to -3 SD vs. WAZ >-2SD: aHR 1.46, 1.31-1.63), complete vaccination (aHR 0.74, 0.60-0.91), wheeze (aHR 0.87, 0.78-0.98) and anaemia (aHR 2.14, 1.89-2.43) were independently associated with mortality. CONCLUSIONS: Children readmitted with severe pneumonia account for a substantial proportion of pneumonia hospitalisations and deaths. Further research is required to develop evidence-based approaches to screening, case management, and follow-up of children with severe pneumonia, prioritising those with underlying risk factors for readmission and mortality.

Integrative analyses identify opportunistic pathogens of patients with lower respiratory tract infections based on metagenomic next-generation sequencing.

Lower respiratory tract infections (LRTIs) represent some of the most globally prevalent and detrimental diseases. Metagenomic next-generation sequencing (mNGS) technology has effectively addressed the requirement for the diagnosis of clinical infectious diseases. This study aimed at identifying and classifying opportunistic pathogens from the respiratory tract-colonizing microflora in LRTI patients using data acquired from mNGS analyses. A retrospective study was performed employing the mNGS data pertaining to the respiratory samples derived from 394 LRTIs patients. Linear discriminant analysis effect size (LEfSe) analysis was conducted to discern the discriminant bacteria. Receiver operating characteristic curves (ROC) were established to demonstrate discriminant bacterial behavior to distinguish colonization from infection. A total of 443 discriminant bacteria were identified and segregated into three cohorts contingent upon their correlation profiles, detection frequency, and relative abundance in order to distinguish pathogens from colonizing microflora. Among them, 119 emerging opportunistic pathogens (cohort 2) occupied an average area under the curve (AUC) of 0.976 for exhibiting the most prominent predictability in distinguishing colonization from infection, 39 were colonizing bacteria (cohort 1, 0.961), and 285 were rare opportunistic pathogens (cohort 3, 0.887). The LTRIs patients appeared modular in the form of cohorts depicting complex microbial co-occurrence networks, reduced diversity, and a high degree of antagonistic interactions in the respiratory tract microbiome. The study findings indicate that therapeutic interventions should target interaction networks rather than individual microbes, providing an innovative perspective for comprehending and combating respiratory infections. Conclusively, this study reports a profile of LRTIs-associated bacterial colonization and opportunistic pathogens in a relatively large-scale cohort, which might serve as a reference panel for the interpretation of mNGS results in clinical practice.

Ciprofloxacin-Loaded Inhalable Formulations against Lower Respiratory Tract Infections: Challenges, Recent Advances, and Future Perspectives.

Inhaled ciprofloxacin (CFX) has been investigated as a treatment for lower respiratory tract infections (LRTIs) associated with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and bronchiectasis. The challenges in CFX effectiveness for LRTI treatment include poor aqueous solubility and therapy resistance. CFX dry powder for inhalation (DPI) formulations were well-tolerated, showing a remarkable decline in overall bacterial burden compared to a placebo in bronchiectasis patients. Recent research using an inhalable powder combining Pseudomonas phage PEV20 with CFX exhibited a substantial reduction in bacterial density in mouse lungs infected with clinical P. aeruginosa strains and reduced inflammation. Currently, studies suggest that elevated biosynthesis of fatty acids could serve as a potential biomarker for detecting CFX resistance in LRTIs. Furthermore, inhaled CFX has successfully addressed various challenges associated with traditional CFX, including the incapacity to eliminate the pathogen, the recurrence of colonization, and the development of resistance. However, further exploration is needed to address three key unresolved issues: identifying the right patient group, determining the optimal treatment duration, and accurately assessing the risk of antibiotic resistance, with additional multicenter randomized controlled trials suggested to tackle these challenges. Importantly, future investigations will focus on the effectiveness of CFX DPI in bronchiectasis and COPD, aiming to differentiate prognoses between these two conditions. This review underscores the importance of CFX inhalable formulations against LRTIs in preclinical and clinical sectors, their challenges, recent advancements, and future perspectives.

Inhaled antibiotics: A promising drug delivery strategies for efficient treatment of lower respiratory tract infections (LRTIs) associated with antibiotic resistant biofilm-dwelling and intracellular bacterial pathogens.

Antibiotic-resistant bacteria associated with LRTIs are frequently associated with inefficient treatment outcomes. Antibiotic-resistant Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Staphylococcus aureus, infections are strongly associated with pulmonary exacerbations and require frequent hospital admissions, usually following failed management in the community. These bacteria are difficult to treat as they demonstrate multiple adaptational mechanisms including biofilm formation to resist antibiotic threats. Currently, many patients with the genetic disease cystic fibrosis (CF), non-CF bronchiectasis (NCFB) and chronic obstructive pulmonary disease (COPD) experience exacerbations of their lung disease and require high doses of systemically administered antibiotics to achieve meaningful clinical effects, but even with high systemic doses penetration of antibiotic into the site of infection within the lung is suboptimal. Pulmonary drug delivery technology that reliably deliver antibacterials directly into the infected cells of the lungs and penetrate bacterial biofilms to provide therapeutic doses with a greatly reduced risk of systemic adverse effects. Inhaled liposomal-packaged antibiotic with biofilm-dissolving drugs offer the opportunity for targeted, and highly effective antibacterial therapeutics in the lungs. Although the challenges with development of some inhaled antibiotics and their clinicals trials have been studied; however, only few inhaled products are available on market. This review addresses the current treatment challenges of antibiotic-resistant bacteria in the lung with some clinical outcomes and provides future directions with innovative ideas on new inhaled formulations and delivery technology that promise enhanced killing of antibiotic-resistant biofilm-dwelling bacteria.

Respiratory Syncytial Virus and Influenza Infections in Children in Ulaanbaatar, Mongolia, 2015-2021.

BACKGROUND: Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015 to June 2021. METHODS: This study was nested in an enhanced surveillance project evaluating pneumococcal conjugate vaccine (PCV13) impact on the incidence of hospitalized lower respiratory tract infections (LRTIs). Our study was restricted to children aged < 2 years with arterial O2 saturation < 93% and children with radiological pneumonia. Nasopharyngeal (NP) swabs collected at admission were tested for RSV and influenza using qRT-PCR. NP swabs of all patients with radiological pneumonia and of a subset of randomly selected NP swabs were tested for S. pneumoniae (S.p.) by qPCR and for serotypes by culture and DNA microarray. RESULTS: Among 5705 patients, 2113 (37.0%) and 386 (6.8%) had RSV and influenza infections, respectively. Children aged 2-6 months had a higher percentage of very severe RSV infection compared to those older than 6 months (42.2% versus 31.4%, p-value Fisher's exact = 0.001). S.p. carriage was detected in 1073/2281 (47.0%) patients. Among S.p. carriage cases, 363/1073 (33.8%) had S.p. and RSV codetection, and 82/1073 (7.6%) had S.p. and influenza codetection. S.p. codetection with RSV/influenza was not associated with more severe LRTIs, compared to only RSV/influenza cases. CONCLUSION: In Mongolia, RSV is an important pathogen causing more severe LRTI in children under 6 months of age. Codetection of RSV or influenza virus and S.p. was not associated with increased severity.

The effect of focused lung ultrasonography on antibiotic prescribing in patients with acute lower respiratory tract infections in Danish general practice: study protocol for a pragmatic randomized controlled trial (PLUS-FLUS).

BACKGROUND: The use of antibiotics is a key driver of antimicrobial resistance and is considered a major threat to global health. In Denmark, approximately 75% of antibiotic prescriptions are issued in general practice, with acute lower respiratory tract infections (LRTIs) being one of the most common indications. Adults who present to general practice with symptoms of acute LRTI often suffer from self-limiting viral infections. However, some patients have bacterial community-acquired pneumonia (CAP), a potential life-threatening infection, that requires immediate antibiotic treatment. Importantly, no single symptom or specific point-of-care test can be used to discriminate the various diagnoses, and diagnostic uncertainty often leads to (over)use of antibiotics. At present, general practitioners (GPs) lack tools to better identify those patients who will benefit from antibiotic treatment. The primary aim of the PLUS-FLUS trial is to determine whether adults who present with symptoms of an acute LRTI in general practice and who have FLUS performed in addition to usual care are treated less frequently with antibiotics than those who only receive usual care. METHODS: Adults (≥ 18 years) presenting to general practice with acute cough (< 21 days) and at least one other symptom of acute LRTI, where the GP suspects a bacterial CAP, will be invited to participate in this pragmatic randomized controlled trial. All participants will receive usual care. Subsequently, participants will be randomized to either the control group (usual care) or to an additional focused lung ultrasonography performed by the GP (+ FLUS). The primary outcome is the proportion of participants with antibiotics prescribed at the index consultation (day 0). Secondary outcomes include comparisons of the clinical course for participants in groups. DISCUSSION: We will examine whether adults who present with symptoms of acute LRTI in general practice, who have FLUS performed in addition to usual care, have antibiotics prescribed less frequently than those given usual care alone. It is highly important that a possible reduction in antibiotic prescriptions does not compromise patients' recovery or clinical course, which we will assess closely. TRIAL REGISTRATION: ClinicalTrials.gov NCT06210282. Registered on January 17, 2024.

Seasonal extreme temperatures and short-term fine particulate matter increases pediatric respiratory healthcare encounters in a sparsely populated region of the intermountain western United States.

BACKGROUND: Western Montana, USA, experiences complex air pollution patterns with predominant exposure sources from summer wildfire smoke and winter wood smoke. In addition, climate change related temperatures events are becoming more extreme and expected to contribute to increases in hospital admissions for a range of health outcomes. Evaluating while accounting for these exposures (air pollution and temperature) that often occur simultaneously and may act synergistically on health is becoming more important. METHODS: We explored short-term exposure to air pollution on children's respiratory health outcomes and how extreme temperature or seasonal period modify the risk of air pollution-associated healthcare events. The main outcome measure included individual-based address located respiratory-related healthcare visits for three categories: asthma, lower respiratory tract infections (LRTI), and upper respiratory tract infections (URTI) across western Montana for ages 0-17 from 2017-2020. We used a time-stratified, case-crossover analysis with distributed lag models to identify sensitive exposure windows of fine particulate matter (PM2.5) lagged from 0 (same-day) to 14 prior-days modified by temperature or season. RESULTS: For asthma, increases of 1 µg/m3 in PM2.5 exposure 7-13 days prior a healthcare visit date was associated with increased odds that were magnified during median to colder temperatures and winter periods. For LRTIs, 1 µg/m3 increases during 12 days of cumulative PM2.5 with peak exposure periods between 6-12 days before healthcare visit date was associated with elevated LRTI events, also heightened in median to colder temperatures but no seasonal effect was observed. For URTIs, 1 unit increases during 13 days of cumulative PM2.5 with peak exposure periods between 4-10 days prior event date was associated with greater risk for URTIs visits that were intensified during median to hotter temperatures and spring to summer periods. CONCLUSIONS: Delayed, short-term exposure increases of PM2.5 were associated with elevated odds of all three pediatric respiratory healthcare visit categories in a sparsely population area of the inter-Rocky Mountains, USA. PM2.5 in colder temperatures tended to increase instances of asthma and LRTIs, while PM2.5 during hotter periods increased URTIs.

Impact of pneumococcal conjugate vaccine 13 introduction on severe lower respiratory tract infections associated with respiratory syncytial virus or influenza virus in hospitalized children in Ulaanbaatar, Mongolia.

Objectives: Limited data indicate a beneficial effect of pneumococcal conjugate vaccines (PCVs) on respiratory syncytial virus (RSV) and influenza infections in young children. We evaluated the impact of 13-valent PCV (PCV13) introduction on the incidence of severe lower respiratory tract infections (LRTIs) associated with RSV or influenza in hospitalized children. Methods: Our study was restricted to children aged <2 years with arterial oxygen saturation <93% and children with radiologically confirmed pneumonia nested in a pneumonia surveillance project in four districts of Ulaanbaatar city, Mongolia. We tested nasopharyngeal swabs collected on admission for RSV and influenza using quantitative reverse transcription-polymerase chain reaction. The impact of PCV13 on the incidence of LRTI outcomes associated with RSV or with influenza for the period April 2015-March 2020 was estimated. Incidence rate ratios comparing pre- and post-vaccine periods were estimated for each outcome for each district using negative binomial models and for all districts combined with a mixed-effects negative binomial model. Adjusted models accounted for seasonality. Sensitivity analyses were conducted to assess the robustness of our findings. Results: Among 5577 tested cases, the adjusted incidence rate ratios showed a trend toward a reduction in RSV-associated outcomes: all LRTIs (0.77, 95% confidence interval [CI] 0.44-1.36), severe LRTIs (0.88, 95% CI 0.48-1.62), very severe LRTIs (0.76, 95% CI 0.42-1.38), and radiologically confirmed pneumonia (0.66, 95% CI 0.32-1.38) but inconsistent trends in outcomes associated with influenza. Conclusions: No significant reductions were observed in any outcomes associated with RSV and influenza after PCV introduction.

Microbial aetiology of community-acquired pneumonia in hospitalised adults: A prospective study utilising comprehensive molecular testing.

OBJECTIVES: This study aimed to describe the microbial aetiology of community-acquired pneumonia (CAP) in adults admitted to a tertiary care hospital and assess the impact of syndromic polymerase chain reaction (PCR) panels on pathogen detection. METHODS: Conducted at Haukeland University Hospital, Norway, from September 2020 to April 2023, this prospective study enrolled adults with suspected CAP. We analysed lower respiratory tract samples using both standard-of-care tests and the BIOFIRE® FILMARRAY® Pneumonia Plus Panel (FAP plus). The added value of FAP Plus in enhancing the detection of clinically relevant pathogens, alongside standard-of-care diagnostics, was assessed. RESULTS: Of the 3238 patients screened, 640 met the inclusion criteria, with 384 confirmed to have CAP at discharge. In these patients, pathogens with proven or probable clinical significance were identified in 312 (81.3%) patients. Haemophilus influenzae was the most prevalent pathogen, found in 118 patients (30.7%), followed by SARS-CoV-2 in 74 (19.3%), and Streptococcus pneumoniae in 64 (16.7%). Respiratory viruses were detected in 186 (48.4%) patients. The use of FAP plus improved the pathogen detection rate from 62.8% with standard-of-care methods to 81.3%. CONCLUSIONS: Pathogens were identified in 81% of CAP patients, with Haemophilus influenzae and respiratory viruses being the most frequently detected pathogens. The addition of the FAP plus panel, markedly improved pathogen detection rates compared to standard-of-care diagnostics alone.

Viral etiology of severe lower respiratory tract infections in SARS-CoV-2 negative hospitalized patients during the COVID-19 pandemic in Kuwait.

Background: The prevalence of respiratory infections is largely underexplored in Kuwait. The aim of our study is to determine the etiology of infections from patients who are SARS-CoV-2 negative hospitalized with severe lower respiratory tract infections (LRTIs) in Kuwait during the coronavirus disease 2019 (COVID-19) pandemic. Methods: We conducted an observational cross-sectional study among severe LRTI patients between September 2021 and March 2022. Respiratory samples from 545 non-COVID-19 severe LRTIs patients were prospectively evaluated with FTD Respiratory 21 Plus® real-time PCR, targeting 20 different viruses and 1 atypical bacterial pathogen. Results: Among all 545 hospitalized cases, 411 (75.4 %) tested positive for at least one respiratory pathogen. The most common were rhinovirus (HRV) (32.7 %), respiratory syncytial virus (RSV) (20.9 %), metapneumovirus (HMPV) (14.1 %), bocavirus (13.2 %), and influenza A (12.7 %). The proportion of pathogens detected was highest in the under-5 age group, while HKU1 (44.4 %) predominated in the elderly (>50 years). Conclusion: Our study reveals a high prevalence of respiratory viruses in severe acute lower respiratory tract infections among non-COVID-19 hospitalized patients in Kuwait. HRV remains the main etiology affecting the country, particularly in infants. These results underscore the necessity of employing multiplex PCR for accurate diagnosis and describing the epidemiology of infections among severe lower respiratory tract infections. This will facilitate the use of specific antiviral therapy and help avoid excessive or inappropriate antibiotic therapy.

Parental engagement in research on paediatric lower respiratory tract infections in Indonesia.

BACKGROUND: Lower respiratory tract infections (LRTIs) in children are a major concern in Indonesia as it is the leading cause of morbidity and mortality. Therefore, research on LRTIs is crucial to improve children's health. However, clinical research in children is challenging due to parental concerns. This study aims to understand parental considerations for taking part in clinical studies on LRTI in the Indonesian context. METHODS: A cross-sectional study using a validated online questionnaire was conducted from November 2021 to March 2022. This study included parents from two public elementary schools and two private primary schools in Semarang, Indonesia. A total of 1236 responses were analysed. RESULTS: There was a significant association between educational attainment and willingness to participate in general health and LRTI-related research requiring specimen collection; respondents with an advanced educational level were more likely to refuse participation in research. A similar pattern was observed among respondents with smaller families and younger children against participation in LRTI research. Most respondents who indicated not to participate explained that they did not perceive the necessity to take part and expressed their concerns about endangering their child's health as a consequence of the specimen collection. Most respondents expected a personal benefit and prioritized access to the study results for their child. CONCLUSION: Parents' educational background and family composition are important determinants of parental engagement in research on LRTI in Indonesia. Notably, parents with a lower educational level, having large families, and older children were more inclined to participate. The emphasis on concerns about potential harm and personal benefit underscores the need for a targeted communication strategy.

Spectrum of pathogens and their antimicrobial susceptibility pattern isolated from bronchoalveolar lavage specimens at a hilly area in Uttarakhand.

Background: Lower respiratory tract infections (LRTIs) are associated with significant morbidity and mortality in all age groups, especially young children and the elderly population. Various gram-positive and gram-negative organisms such as Streptococcus spp., Pseudomonas spp., and Klebsiella spp. have been implicated as a pathogen in bronchoalveolar lavage (BAL) specimens collected from such patients. Aims and Rationale of the Study: The present study is aimed at assessing the spectrum of the bacterial isolates and determining the antimicrobial resistance obtained from the BAL fluid from admitted patients at various wards and intensive care units (ICUs) of a tertiary care hospital in Dehradun. This will be the stepping stone in our efforts toward becoming a future antimicrobial steward and framing local antibiograms based on such data. Material and Methods: Two hundred BAL specimens were collected from patients admitted to various wards and ICUs of the hospital who were suffering from LRTI. The BAL specimens were subjected to direct microscopy and culture. Identification and susceptibility testing were performed. Results: The most predominant isolates were Pseudomonas aeruginosa (16/39 (41.02%)) followed by Klebsiella pneumoniae (7/39 (17.94%)) and Acinetobacter spp. (6/39 (15.38%)). Sixty-five percentage of Pseudomonas aeruginosa, 71% of Klebsiella pneumoniae, and 83% of Acinetobacter spp. showed intermediate results with colistin. Conclusion: Nonfermenters constitute a significant group of organisms isolated from bronchoalveolar lavage (BAL) specimens in patients with lower respiratory tract infections (LRTIs). Hence, it is extremely important to correctly identify and determine the resistance pattern of such isolates so that appropriate empirical therapy can be initiated for the benefit of the patient.

Risk factors associated with functional decline in older hospital survivors with acute lower respiratory tract infections: a prospective cohort study.

OBJECTIVE: To evaluate the dynamics of basic activity of daily living (BADL) in older patients with acute lower respiratory tract infections (LRTIs) during acute phase and to investigate risk factors associated with decreased physical function at discharge. METHODS: We conducted a prospective cohort study of patients aged 65 years and older who were hospitalized for acute LRTIs between April 15, 2020 and January 15, 2023. All patients received geriatric assessment at admission, including emotion, cognition, frailty, physical function status and so on. The BADL was also evaluated by the Barthel Index (BI) at two weeks before admission by recall (baseline status), at admission and at discharge. Based on the BI grades at baseline and at discharge, patients were classified into two groups: ADL decline and no ADL decline. Multivariable adjusted logistic regression models were used to evaluate the risk factors of decreased physical function. RESULTS: A total of 364 older survivors with LRTIs were included in the analysis. The median age was 74 years (IQR 61.0-82.0), 231 (62.6%) were male, the median length of stay was 10 days. In the geriatric assessment, 139 patients (38.2%) were classified as frailty, 137 patients (37.6%) experienced insomnia, 60 patients (16.5%) exhibited cognitive impairments, and 37 patients (10.2%) were defined as malnutrition. Additionally, 30 patients (8.2%) dealt with emotional disorders. On average, patients were taking 3 medications, and Charlson Comorbidity Index score was 4. 72 patients (19.8%) had function decline at discharge. In the multivariable analysis, frailty status had an odds ratio of 4.25 (95% CI 1.31-19.26) for decreased physical function and cognitive impairment had an odds ratio of 2.58 (95% CI 1.27-5.19). CONCLUSIONS: About 20% older patients with LRTIs experienced functional decline at discharge. Compared to age, severity of diseases and length of stay, frailty and cognitive impairment performed better at predicting the function decline. The apply of geriatric assessment may contribute to enhance the quality of management and treatment for patients with the older with LRTIs.