Lower Respiratory Tract Research Articles

Emerging importance of multidrug-resistant Stenotrophomonas maltophilia infections in neonatal intensive care unit in a tertiary center in Turkey

Stenotrophomonas maltophilia is an emerging multi-drug resistant, opportunistic pathogen in the neonatal intensive care unit (NICU). In this study, we aimed to assess the incidence, clinical features, antibiotic susceptibility, and treatment options of S. maltophilia infection among the healthcare-associated infections (HAIs) in the neonatal unit. In this study, the patients who were hospitalized in the NICU between January 2020 and December 2021 with S. maltophilia isolated from clinical samples were included. Demographic, clinic features, and microbiological findings of the patients were retrospectively evaluated by using the medical records. The samples (lower respiratory tract, urine, peritoneal fluid) were first examined microscopically by gram preparation and cultured. Antibiotic susceptibility tests were performed according to the recommendations of The European Committee on Antimicrobial Susceptibility Testing (EUCAST) for TMP-SMX. S. maltophilia was isolated in 38 clinical samples of the 20 patients who were hospitalized at the NICU between January 2020 and December 2021. A total of 40% (n=8) of samples from different patients were accepted as colonization. Ventilator-associated pneumonia was determined in 55% (n=11), and urinary tract infection in 5% (n=1). S. maltophilia-associated bacteremia was not detected in any of the cases. The TMP-SMX susceptibilities of the strains were as it follows: 3 (15%) were resistant (R), 7 (28%) were susceptible (S), and 10 (47%) were susceptible-increased exposure (I). Three of these patients were given dual antibiotics therapy (levofloxacin plus TMP-SMX) and nine of them were given only TMP-SMX. The most common hospital-acquired infectious agents are Gram negative microorganisms (51%), followed by coagulase negative staphylococci (CNS), Staphylococcus aureus (24%) and S. maltophilia (24%). Increasing TMP-SMX resistance and specific drug and dosage-related problems in the neonatal unit are important problems in treatment management.

Treatments and Outcomes of Critically Ill Patients with Candida spp. Colonization of the Lower Respiratory Tract in Regina, Saskatchewan.

Among critically ill patients receiving mechanical ventilation, Candida spp. are commonly detected in the lower respiratory tract (LRT). This is generally considered to represent colonization. To evaluate the use of antifungal treatments and the clinical outcomes of patients with Candida colonization of the LRT. This retrospective analysis involved consecutive patients admitted to the intensive care unit between April 2016 and May 2021with positive results on Candida spp. testing of LRT samples. Data related to antifungal treatment and clinical outcomes were analyzed descriptively, and multivariable logistic regression was performed. Of 200 patients initially identified, 160 (80%) died in hospital. Antifungal therapy was given to 103 (51.5%) of the patients, with treatment being more likely among those with shock and those who received parenteral nutrition. Mortality was high among patients with positive Candida results on LRT culture, regardless of treatment. Multivariable logistic regression, with adjustment for age, sex, comorbidities, and sequential organ failure assessment (SOFA) score, showed that antifungal treatment was associated with lower odds of death (odds ratio 0.39, 95% confidence interval 0.17-0.87) compared with no treatment (p = 0.021). This study showed higher mortality rates than have been reported previously. Further investigation into the role of antifungal therapy among critically ill patients with Candida spp. colonization is required.

Circ_0026579 knockdown ameliorates lipopolysaccharide-induced human lung fibroblast cell injury by regulating CXCR1 via miR-370-3p.

Pneumonia is an inflammatory disease in lower respiratory tracts and its development involves the regulation of RNAs. Circular RNAs are a class of RNA subgroups that can mediate the progression of pneumonia. However, the molecular mechanism of circ_0026579 in regulating pneumonia occurrence remains unclear. The study is designed to reveal the role of circ_0026579 in lipopolysaccharide (LPS)-induced human lung fibroblast cell injury and the underlying mechanism. The expression levels of circ_0026579, miR-370-3p and C-X-C motif chemokine receptor 1 (CXCR1) were detected by quantitative real-time polymerase chain reaction or by western blotting. The production of tumour necrosis factor-α, interleukin (IL)-1β and IL-6 was assessed by enzyme-linked immunosorbent assays. Malondialdehyde and superoxide dismutase levels were analysed using commercial kits. Cell viability, proliferation and apoptosis were analysed by cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine assay and flow cytometry analysis, respectively. The binding relationship between miR-370-3p and circ_0026579 or CXCR1 was identified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Circ_0026579 and CXCR1 expression were significantly upregulated, whereas miR-370-3p was downregulated in the serum of pneumonia patients. LPS treatment induced inflammatory response, oxidative stress and cell apoptosis and inhibited cell proliferation in MRC-5 cells; however, these effects were reversed after circ_0026579 depletion. In terms of the mechanism, circ_0026579 acted as a miR-370-3p sponge, and miR-370-3p combined with CXCR1. Additionally, circ_0026579 depletion ameliorated LPS-induced MRC-5 cell disorder by increasing miR-370-3p expression. CXCR1 overexpression also relieved the miR-370-3p-mediated effects in LPS-treated MRC-5 cells. Further, circ_0026579 induced CXCR1 expression by interacting with miR-370-3p. Circ_0026579 absence ameliorated MRC-5 cell dysfunction induced by LPS through the regulation of the miR-370-3p/CXCR1 axis.

Synergistic Antibiofilm Action of Cinnamomum verum and Brazilian Green Propolis Hydroethanolic Extracts against Multidrug-Resistant Strains of Acinetobacter baumannii and Pseudomonas aeruginosa and Their Biocompatibility on Human Keratinocytes.

The accumulated dental biofilm can be a source of oral bacteria that are aspirated into the lower respiratory tract causing ventilator-associated pneumonia in hospitalized patients. The aim of this study was to evaluate the synergistic antibiofilm action of the produced and phytochemically characterized extracts of Cinnamomum verum and Brazilian green propolis (BGP) hydroethanolic extracts against multidrug-resistant clinical strains of Acinetobacter baumannii and Pseudomonas aeruginosa, in addition to their biocompatibility on human keratinocyte cell lines (HaCaT). For this, High-performance liquid chromatography analysis of the plant extracts was performed; then the minimum inhibitory and minimum bactericidal concentrations of the extracts were determined; and antibiofilm activity was evaluated with MTT assay to prevent biofilm formation and to reduce the mature biofilms. The cytotoxicity of the extracts was verified using the MTT colorimetric test, evaluating the cellular enzymatic activity. The data were analyzed with one-way ANOVA and Tukey's tests as well as Kruskal-Wallis and Dunn's tests, considering a significance level of 5%. It was possible to identify the cinnamic aldehyde in C. verum and p-coumaric, caffeic, and caffeoylquinic acids as well as flavonoids such as kaempferol and kaempferide and Artepillin-C in BGP. The combined extracts were effective in preventing biofilm formation and reducing the mature biofilms of A. baumannii and P. aeruginosa. Moreover, both extracts were biocompatible in different concentrations. Therefore, C. verum and BGP hydroethanolic extracts have bactericidal and antibiofilm action against multidrug resistant strains of A. baumannii and P. aeruginosa. In addition, the combined extracts were capable of expressively inhibiting the formation of A. baumannii and P. aeruginosa biofilms (prophylactic effect) acting similarly to 0.12% chlorhexidine gluconate.

Etiological Bacterial Spectrum of Purulent Inflammation of Cervical Lymph Nodes in Children With Unknown Causes of Lymphadenopathy.

In the management of the non-specific purulent inflammation of the cervical lymph nodes in children, not only surgical treatment to evacuate the available pusbut also antibacterial therapy is mandatory. Knowledge of the spectrum of the bacterial causative agents of this disease is of fundamental importance for it. This retrospective study included 66 patients with purulent inflammation of the cervical lymph nodes with a mean age of 5.79 years, ranging from 29 days to 17 years, who were hospitalized for the period 2015-2022 in the three pediatric clinics at the St. Marina University Multispecialty Hospital for Active Treatment in Varna, Bulgaria, and operated by an oral or maxillofacial surgeon, in which for microbiological examination material from the suppurated lymph node was taken and analyzed first by direct microscopy for gram-positivity and then on a biochemical machine identifier VITEK(bioMérieux, Marcy-l'Étoile, France). In all of them, the patients and their parents did not provide anamnestic data explaining the etiology of their infectious diseases of the cervical lymph nodes. There was no clear cause that would explain the occurrence of cervical lymphadenopathy - skin infections, dental diseases, diseases of the ears and upper and lower respiratory tracts, onco-hematological diseases, and others. During the medical examination by pediatricians and surgeons, no entrances to the infection were found, but only local signs of inflammation (redness, swelling, and pain), increased levels of blood markers of inflammation (leukocytes, neutrophils, erythrocyte sedimentation rate, and C-reactive protein) and there was imaging evidence (ultrasound, magnetic resonance imaging, and computed tomography) of a purulent collection in the lymph nodes and/or in the soft tissues surrounding them. Exudate without microbial growth was found in 22 of the cases. The main causative agents of purulent lymphadenopathy are gram-positive bacteria (n=32, 72,73%) - Staphylococcus aureus (n=16), Staphylococcus haemolyticus (n=8), Beta-hemolytic streptococcus(n=2), and gram-positive mixed resident microflora (n=6). However, in 27.27% (n=12) of all 44 patients described in this article with isolated pathogens, cultures were gram-negative. These are Bartonella henselae (n=4), Klebsiella pneumoniae (n=4), Klebsiella oxytoca (n=2), and Flavimonas oryzihabitans (n=2).

The complexation of atmospheric Brown carbon surrogates on the generation of hydroxyl radical from transition metals in simulated lung fluid

Atmospheric particulate matter (PM) poses great adverse effects through the production of reactive oxygen species (ROS). Various components in PM are acknowledged to induce ROS formation, while the interactions among chemicals remain to be elucidated. Here, we systematically investigate the influence of Brown carbon (BrC) surrogates (e.g., imidazoles, nitrocatechols and humic acid) on hydroxyl radical (OH) generation from transition metals (TMs) in simulated lung fluid. Present results show that BrC has an antagonism (interaction factor: 20–90 %) with Cu2+ in OH generation upon the interaction with glutathione, in which the concentrations of BrC and TMs influence the extent of antagonism. Rapid OH generation in glutathione is observed for Fe2+, while OH formation is very little for Fe3+. The compositions of antioxidants (e.g., glutathione, ascorbate, urate), resembling the upper and lower respiratory tract, respond differently to BrC and TMs (Cu2+, Fe2+ and Fe3+) in OH generation and the degree of antagonism. The complexation equilibrium constants and site numbers between Cu2+ and humic acid were further analyzed using fluorescence quenching experiments. Possible complexation products among TMs, 4-nitrocatechol and glutathione were also identified using quadropule-time-of-flight mass spectrometry. The results suggest atmospheric BrC widely participate in complexation with TMs which influence OH formation in the human lung fluid, and complexation should be considered in evaluating ROS formation mediated by ambient PM.

SARS-CoV-2 Infection and Postacute Risk of Non-Coronavirus Disease 2019 Infectious Disease Hospitalizations: A Nationwide Cohort Study of Danish Adults Aged ≥50 Years.

Reports suggest that the potential long-lasting health consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may involve persistent dysregulation of some immune populations, but the potential clinical implications are unknown. We investigated the associated risk of hospitalization due to non-coronavirus disease 2019 (COVID-19) infectious diseases following the postacute phase of SARS-CoV-2 infection. By cross-linking data from the comprehensive Danish test and surveillance system for COVID-19 together with nationwide healthcare and demographic registers, we established a study cohort of 2 430 694 individuals aged ≥50 years, from 1 January 2021 to 10 December 2022, with no evidence of SARS-CoV-2 infection prior to study entry. Using Poisson regression, we compared the outcome rates of non-COVID-19 infectious disease hospitalizations following the acute phase of (a first) SARS-CoV-2 infection (defined as ≥29 days since the day of infection) in recovered individuals with rates among SARS-CoV-2-uninfected individuals. Among 2 430 694 included individuals (mean age, 66.8 [standard deviation, 11.3] years), 930 071 acquired SARS-CoV-2 infection during follow-up totaling 4 519 913 person-years. The postacute phase of SARS-CoV-2 infection was associated with an incidence rate ratio (IRR) of 0.90 (95% confidence interval [CI]: .88-.92) for any infectious disease hospitalization. Findings (IRR [95% CI]) were similar for upper respiratory tract (1.08 [.97-1.20]), lower respiratory tract (0.90 [.87-.93]), influenza (1.04 [.94-1.15]), gastrointestinal (1.28 [.78-2.09]), skin (0.98 [.93-1.03]), urinary tract (1.01 [.96-1.08]), certain invasive bacterial (0.96 [.91-1.01]), and other (0.96 [.92-1.00]) infectious disease hospitalizations and in subgroups. Our study does not support an increased susceptibility to non-COVID-19 infectious disease hospitalization following SARS-CoV-2 infection.

Viral Detection by Reverse Transcriptase Polymerase Chain Reaction in Upper Respiratory Tract and Metagenomic RNA Sequencing in Lower Respiratory Tract in Critically Ill Children With Suspected Lower Respiratory Tract Infection.

Viral lower respiratory tract infection (vLRTI) contributes to substantial morbidity and mortality in children. Diagnosis is typically confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal specimens in hospitalized patients; however, it is unknown whether nasopharyngeal detection accurately reflects presence of virus in the lower respiratory tract (LRT). This study evaluates agreement between viral detection from nasopharyngeal specimens by RT-PCR compared with metagenomic next-generation RNA sequencing (RNA-Seq) from tracheal aspirates (TAs). This is an analysis of of a seven-center prospective cohort study. Seven PICUs within academic children's hospitals in the United States. Critically ill children (from 1 mo to 18 yr) who required mechanical ventilation via endotracheal tube for greater than or equal to 72 hours. We evaluated agreement in viral detection between paired upper and LRT samples. Results of clinical nasopharyngeal RT-PCR were compared with TA RNA-Seq. Positive and negative predictive agreement and Cohen's Kappa were used to assess agreement. Of 295 subjects with paired testing available, 200 (68%) and 210 (71%) had positive viral testing by RT-PCR from nasopharyngeal and RNA-Seq from TA samples, respectively; 184 (62%) were positive by both nasopharyngeal RT-PCR and TA RNA-Seq for a virus, and 69 (23%) were negative by both methods. Nasopharyngeal RT-PCR detected the most abundant virus identified by RNA-Seq in 92.4% of subjects. Among the most frequent viruses detected, respiratory syncytial virus demonstrated the highest degree of concordance (κ = 0.89; 95% CI, 0.83-0.94), whereas rhinovirus/enterovirus demonstrated lower concordance (κ = 0.55; 95% CI, 0.44-0.66). Nasopharyngeal PCR was more likely to detect multiple viruses than TA RNA-Seq (54 [18.3%] vs 24 [8.1%], p ≤ 0.001). Viral nucleic acid detection in the upper versus LRT reveals good overall agreement, but concordance depends on the virus. Further studies are indicated to determine the utility of LRT sampling or the use of RNA-Seq to determine LRTI etiology.

Susceptibility of gram-negative isolates collected in Taiwan to imipenem/relebactam and comparator agents – SMART 2018–2021

Imipenem/relebactam (IMR) was approved for patient use in Taiwan in 2023. We evaluated the invitro susceptibility of recent Gram-negative pathogens collected in Taiwan hospitals to IMR and comparators with a focus on carbapenem-resistant and KPC-carrying non-Morganellaceae Enterobacterales (NME), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). From 2018 to 2021, eight hospitals in Taiwan each collected up to 250 consecutive, aerobic or facultative, Gram-negative pathogens per year from patients with bloodstream, intraabdominal, lower respiratory tract, and urinary tract infections. MICs were determined using Clinical Laboratory Standards Institute (CLSI) broth microdilution. Most isolates that were IMR-, imipenem-, or ceftolozane/tazobactam-nonsusceptible were screened for β-lactamase genes by PCR or whole-genome sequencing. Ninety-eight percent of NME (n=5063) and 94% of P. aeruginosa (n=1518) isolates were IMR-susceptible. Percent susceptible values for non-carbapenem β-lactam comparators, including piperacillin/tazobactam, were 68-79% for NME isolates, while percent susceptible values for all β-lactam comparators, including meropenem, were 73-81% for P. aeruginosa. IMR retained activity against 93% of multidrug-resistant (MDR) NME and 70% of MDR P. aeruginosa. Sixty-five percent of carbapenem-resistant NME and 81% of KPC-positive NME (n=80) were IMR-susceptible. IMR inhibited 70% of CRPA (n=287). Fifty percent of IMR-nonsusceptible NME tested for β-lactamase carriage had an MBL or OXA-48-like enzyme, whereas most (95%) IMR-nonsusceptible P. aeruginosa examined did not carry acquired β-lactamase genes. Based on our invitro data, IMR may be a useful option for the treatment of hospitalized patients in Taiwan with infections caused by common Gram-negative pathogens, including carbapenem-resistant NME, KPC-positive NME, and CRPA.

Impact of bronchoalveolar lavage on the management of immunocompromised hosts

BackgroundRespiratory infections are an important cause of morbidity and mortality in immunocompromised individuals. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) is an important tool to detect infectious agents in immunocompromised patients with low respiratory tract infections (LRTI). Research QuestionBAL changes the management of immunocompromised patients with suspected LRTI. Study Design and MethodsImmunocompromised patients with a suspicion of LRTI underwent diagnostic BAL. The primary composite outcome consisted of pre-defined modifications in the management of the immunocompromised patients following BAL. We quantified the impact of bronchoscopy up to 30 days after the procedure. ResultsA total of 2666 visits from 1301 patients were included in the study and immunosuppression was classified as haematological (n = 1040; 544 patients), solid organ transplantation (n = 666; 107 patients) and other causes (n = 960; 650 patients). BAL led to a change in management in 52.36% (n = 1396) of all cases. This percentage, as well as the 30-day mortality differed significantly amongst the three groups. Age, C-reactive protein and aetiology of infection determined significantly the risk of 30-day mortality in all patients. In 1.89% (n = 50) of all cases, a combination of 2 respiratory viral agents was identified and 24.23% (n = 646) were diagnosed with a single respiratory viral agent. InterpretationBAL leads to changes in management in the majority of immunosuppressed patients. There is a high prevalence of multimicrobial infections and respiratory viral infections in immunocompromised patients with respiratory symptoms. Individual virus infection is associated with diverse risk of a negative outcome.

TLR7 promotes chronic airway disease in RSV-infected mice.

Respiratory syncytial virus (RSV) commonly infects the upper respiratory tract (URT) of humans, manifesting with mild cold or flu-like symptoms. However, in infants and the elderly, severe disease of the lower respiratory tract (LRT) often occurs and can develop into chronic airway disease. A better understanding of how an acute RSV infection transitions to a LRT chronic inflammatory disease is critically important to improve patient care and long-term health outcomes. To model acute and chronic phases of the disease, we infected wild-type C57BL/6 and toll-like receptor 7 knockout (TLR7 KO) mice with RSV and temporally assessed nasal, airway and lung inflammation for up to 42 days post-infection. We show that TLR7 reduced viral titers in the URT during acute infection but promoted pronounced pathogenic and chronic airway inflammation and hyperreactivity in the LRT. This study defines a hitherto unappreciated molecular mechanism of lower respiratory pathogenesis to RSV, highlighting the potential of TLR7 modulation to constrain RSV pathology to the URT.

Unilateral diaphragmatic palsy and pleuropericarditis in a patient with granulomatosis with polyangiitis: a case report

BackgroundGranulomatosis with polyangiitis (GPA) is a rare small vessel vasculitis predominantly affecting upper and lower respiratory tract and kidneys. Unilateral diaphragmatic palsy could be a rare manifestation of GPA. Here we report a case of GPA in a 45-year-old male with unilateral diaphragmatic palsy with pleuropericarditis.Case presentationWe report a case of a 45-year-old Khas male who presented with acute onset chest pain and shortness of breath who had elevated right hemidiaphragm, bilateral pleural effusion and pericardial effusion who was later diagnosed as GPA.ConclusionsGPA should be suspected in all patients with diaphragmatic palsy and pleuropericarditis with appropriate clinical and laboratory picture.

The Clinical Significance of Aspergillus Detected in Lower-Respiratory-Tract Samples of Critically Ill COVID-19-Positive Patients.

Objective: Critically ill patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications, including invasive aspergillosis. Our study aimed to characterize the clinical significance and outcome of Aspergillus species isolated from lower-respiratory-tract samples of critically ill OVID-19 patients at a single center. Design: We conducted a retrospective cohort study to evaluate the characteristics of patients with COVID-19 and aspergillus isolated from the lower respiratory tract and to identify predictors of outcomes in this population. Setting: The setting was a single-center hospital system within the metropolitan Detroit region. Results: The prevalence of Aspergillus isolated in hospitalized COVID-19 patients was 1.18% (30/2461 patients), and it was 4.6% in critically ill ICU patients with COVID-19. Probable COVID-19-associated invasive pulmonary aspergillosis (CAPA) was found in 21 critically ill patients, and 9 cases were classified as colonization. The in-hospital mortality of critically ill patients with CAPA and those with aspergillus colonization were high but not significantly different (76% vs. 67%, p = 1.00). Furthermore, the in-hospital mortality for ICU patients with or without Aspergillus isolated was not significantly different 73.3% vs. 64.5%, respectively (OR 1.53, CI 0.64-4.06, p = 0.43). In patients in whom Aspergillus was isolated, antifungal therapy (p = 0.035, OR 12.3, CI 1.74-252); vasopressors (0.016, OR 10.6, CI 1.75-81.8); and a higher mSOFA score (p = 0.043, OR 1.29 CI 1.03-1.72) were associated with a worse outcome. In a multivariable model adjusting for other significant variables, FiO2 was the only variable associated with in-hospital mortality in patients in whom Aspergillus was isolated (OR 1.07, 95% CI 1.01-1.27). Conclusions: The isolation of Aspergillus from lower-respiratory-tract samples of critically ill patients with COVID-19 is associated with high mortality. It is important to have a low threshold for superimposed infections such as CAPA in critically ill patients with COVID-19.

Efficacy of Raphamin against Pneumococcal Infection: a Preclinical Study.

The aim of the study was to evaluate the activity of Raphamin in a model of non-lethal pneumococcal infection caused by Streptococcus pneumoniae 3 in BALB/c mice. The drug or placebo was administered intragastrically 3 days prior to infection, 2 h before and 2 h post infection, and then for 3 full days, alone or in combination with antibiotic (amoxicil-lin/clavulanic acid). Raphamin monotherapy significantly decreased bacterial load in the lungs in comparison with placebo (p<0.05) which was comparable to the effect in antibiotic alone or combined with Raphamin. Raphamin prevented reproduction of Streptococcus pneumoniae in the lower respiratory tract and its combination with the antibiotic was safe and did not reduce the efficacy of amoxicillin/clavulanic acid.

Prevalence and association of sIgA in saliva and Pseudomonas aeruginosa infection in TB patients: a cross-sectional study

Abstract Objectives Pseudomonas aeruginosa is pathogenic in immunocompromised individuals. It has several complex mechanisms for evading human immunity. The objective of the study was to examine the secretory immunoglobulin A (sIgA) mediated immune response in saliva to detect P. aeruginosa in pulmonary tuberculosis. Methods The infection with P. aeruginosa was categorized according to the Leeds criteria in the final 86 individuals who were proven to have pulmonary tuberculosis by polymerase chain reaction. Levels of serum immunoglobulin G (IgG) and sIgA which are specific to P. aeruginosa were measured using the method of ELISA. Results Patients in the “free of infection (patients who were infected with P. aeruginosa in the lower respiratory tract at the beginning of the study later became negative)” and “intermittent colonized (patients who were infected with P. aeruginosa throughout the study)” groups had substantially higher median baseline sIgA levels in saliva and a much greater proportion of sIgA positive than patients who were never colonized (patients who were found to be P. aeruginosa negative throughout the study) (p=0.038). Median baseline IgG level was 10.7 (1.7–145.0), 8.3 (2.5–22.9), and 6.7 (3.3–17.1) for the patients categorized as “intermittent colonization”, “free of infection” and “never colonized”, respectively. After 3 years of study, sIgA level was found in significant high level among the patients with infection of P. aeruginosa (p=0.003). Conclusions Secretory IgA may be readily collected from saliva and is a useful diagnostic technique for determining whether P. aeruginosa infection has occurred.

A nasal vaccine with inactivated whole-virion elicits protective mucosal immunity against SARS-CoV-2 in mice.

Vaccinations are ideal for reducing the severity of clinical manifestations and secondary complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, SARS-CoV-2 continues to cause morbidity and mortality worldwide. In contrast to parenteral vaccines such as messenger RNA vaccines, nasal vaccines are expected to be more effective in preventing viral infections in the upper respiratory tract, the primary locus for viral infection and transmission. In this study, we examined the prospects of an inactivated whole-virion (WV) vaccine administered intranasally against SARS-CoV-2. Mice were immunized subcutaneously (subcutaneous vaccine) or intranasally (nasal vaccine) with the inactivated WV of SARS-CoV-2 as the antigen. The spike protein (S)-specific IgA level was found to be higher upon nasal vaccination than after subcutaneous vaccination. The level of S-specific IgG in the serum was also increased by the nasal vaccine, although it was lower than that induced by the subcutaneous vaccine. The nasal vaccine exhibited a stronger defense against viral invasion in the upper respiratory tract than the subcutaneous vaccine and unimmunized control; however, both subcutaneous and nasal vaccines provided protection in the lower respiratory tract. Furthermore, we found that intranasally administered inactivated WV elicited robust production of S-specific IgA in the nasal mucosa and IgG in the blood of mice previously vaccinated with messenger RNA encoding the S protein. Overall, these results suggest that a nasal vaccine containing inactivated WV can be a highly effective means of protection against SARS-CoV-2 infection.

857 Congenital Pulmonary Airway Malformation: A Case Report of Concealed Malignancy

Abstract Introduction Congenital pulmonary airway malformation (CPAM) is a developmental disorder in which hamartomatous lesions arise in the lower respiratory tract. Large population data suggests the incidence to be between 0.87 and 1.92/10,000 live births. Adults most often present with persistent cough or recurrent LRTIs. Their rarity can lead to misdiagnosis as a cystic lesion. Surgery is the intervention of choice for symptomatic patients. The role of expectant management in asymptomatic patients remains controversial. In adults, resection may be favoured as these lesions are prone to infection and malignancy develops in approximately 1%. Method We present the case of a 44-year-old woman, with shortness of breath and pleuritic chest pain. CT revealed a 9.7 x 5.4cm lucent lesion in the left lower lobe, initially identified as a large bulla or parenchymal cyst. Decision to resect was made post discussion with the patient, who was keen to proceed to surgery, due to ongoing symptoms. Results A left lower lobectomy was performed via VATS. She was discharged on post-operative day 6, made an excellent recovery on 6-week follow-up and has entered surveillance. Histopathology revealed that the cyst was partially lined with respiratory epithelium and palisading histiocytes; favouring a CPAM type 1 diagnosis. Microscopically, there were foci of mucinous lepidic adenocarcinoma. Conclusions It is important to consider CPAM in the differential for cystic lung diseases. Surgical resection should be considered for CPAM regardless of symptoms, due to the uncertainty in diagnosis from imaging alone and the potential for malignant change.

The impact of quantitative and semi-quantitative culture of respiratory tract secretions on clinical decisions in a patient with suspected pneumonia – case study

Pneumonia is one of the most common disease entities treated in the Intensive Care Unit. The standard diagnostic procedure for patients with suspected pneumonia is to evaluate the presence of symptoms of infection, physical examination, imaging, laboratory and microbiological tests, arterial blood gasometry and culture of respiratory tract secretions. In many Intensive Care Units, the preferred method of collecting material from the lower respiratory tract is an endotracheal aspirate. However, its semi-quantitative culture does not distinguish respiratory tract colonization from infection. Samples obtained by bronchoscopy are believed to be more representative of the presence of true pathogens in the lungs.&#x0D; An 87-year-old patient with myasthenia gravis was admitted to the Intensive Care Unit for suspected pneumonia. Laboratory tests showed elevated inflammatory markers and a chest X-ray showed interstitial densities in the left lower lobe. The result of semi-quantitative culture of tracheal aspirate was heavy growth of Staphylococcus aureus and heavy growth of Pseudomonas aeruginosa. The result of the quantitative BAL culture was S.aureus MSSA 105 colony-forming unit (CFU) per ml, Pseudomonas aeruginosa 102 CFU/ml. To consider a microorganism responsible for infection, the number of bacteria cells must exceed a designated threshold. For BAL it is ≥104 CFU/ml, for TA it is ≥106 CFU/ml, for PSB it is ≥ 103/ml. In this case, the cutoff point for identifying the pathogen responsible for the infection was reached only by Staphylococcus aureus (105 CFU/ml), not by Pseudomonas aeruginosa (102 CFU/ml).&#x0D; The final diagnosis was left-sided PN1 pneumonia of S.aureus etiology. A cloxacillin was used for the treatment. Clinical improvement was achieved.&#x0D; The described case proves the advantage of quantitative culture over semi-quantitative culture of respiratory tract secretions. The advantage of bronchoalveolar lavage over tracheal aspirate is also noticeable.

Comorbid infections in patients with spondyloarthritis: frequency, structure and risk factors

Objective: To investigate the frequency, structure, and risk factors of comorbid infections (CI) in patients with spondyloarthritis (SpA).Material and methods. The study included 332 patients with SpA. Patients were interviewed by the investigating physician, and additional information was obtained from medical records.Results and discussion. Respiratory tract (RT) and ear, nose, and throat (ENT) infections ranked first in the structure of CI. Exacerbation of SpA after CI was found in 42% of patients, and more severe CI against the background of SpA was found in 83 patients. 63 cases of severe CI (SCI) were documented, 63.5% of which were infections of the RT and ENT organs. Predictors for the development of lower RT (LRT) and ENT organ infections were the use of biologic disease-modifying antirheumatic drugs (bDMARDs) in general (odds ratio, OR 2.018; 95% confidence interval, CI 1.221-3.335; p=0.006 and OR 1.761; 95% CI 1.1-2.819, respectively; p=0.018) and tumor necrosis factor-α (TNF-α) inhibitors in particular (OR 2.376; 95% CI 1.417-3.983; p=0.001 and OR 1.833; 95% CI 1.123-2.994; p=0.015), and disease duration of more than 5 years (OR 1.774; 95% CI 1.034—3.042; p=0.037 and OR 2.22; 95% CI 1.378-3.576; p=0.001). The risk of developing LRT infection was higher in the presence of chronic lung disease (OR 3.673; 95% CI 1.602-8.425; p=0.002) and Charlesson Comorbidity Index ≥1 (OR 2.381; 95% CI 1.439-3.94; p=0.001), risk of developing ENT organ infections - with the use of &gt;1 bDMARD (OR 2.4; 95% CI 1.199-4.804; p=0.013) and duration of methotrexate therapy over 5 years (OR 2.478; 95% CI 1.053-5.831; p=0.038). Risk factors for the development of SCI were the use of bDMARDs in general (OR 1.941; 95% CI 1.063-3.545; p=0.031) and TNFα in particular (OR 2.246; 95%, CI 1.218-4.139; p=0.01).Conclusion. The problem of CI in SpA is of great importance. The vast majority of patients with SpA should be vaccinated against pneumococcal infection and influenza.

SARS-CoV-2 Reinfections and Long COVID in the Post-Omicron Phase of the Pandemic.

We are reviewing the current state of knowledge on the virological and immunological correlates of long COVID, focusing on recent evidence for the possible association between the increasing number of SARS-CoV-2 reinfections and the parallel pandemic of long COVID. The severity of reinfections largely depends on the severity of the initial episode; in turn, this is determined both by a combination of genetic factors, particularly related to the innate immune response, and by the pathogenicity of the specific variant, especially its ability to infect and induce syncytia formation at the lower respiratory tract. The cumulative risk of long COVID as well as of various cardiac, pulmonary, or neurological complications increases proportionally to the number of SARS-CoV-2 infections, primarily in the elderly. Therefore, the number of long COVID cases is expected to remain high in the future. Reinfections apparently increase the likelihood of long COVID, but less so if they are mild or asymptomatic as in children and adolescents. Strategies to prevent SARS-CoV-2 reinfections are urgently needed, primarily among older adults who have a higher burden of comorbidities. Follow-up studies using an established case definition and precise diagnostic criteria of long COVID in people with or without reinfection may further elucidate the contribution of SARS-CoV-2 reinfections to the long COVID burden. Although accumulating evidence supports vaccination, both before and after the SARS-CoV-2 infection, as a preventive strategy to reduce the risk of long COVID, more robust comparative observational studies, including randomized trials, are needed to provide conclusive evidence of the effectiveness of vaccination in preventing or mitigating long COVID in all age groups. Thankfully, answers not only on the prevention, but also on treatment options and rates of recovery from long COVID are gradually starting to emerge.