Pulmonary tuberculosis (PTB) remains a leading cause of mortality in sub-Saharan Africa but often remains unconfirmed. Patient outcomes in unconfirmed TB or non-TB cases are rarely studied. We assessed 2-month outcomes and associated factors in presumed TB cases independent of TB status. Hospitalized adults with presumed PTB in Lambaréné, Gabon, were prospectively enrolled (September 2024-January 2025). Demographic data, including a socioeconomic status (SES) score, were collected. Laboratory analyses included HIV-test, GeneXpert and mycobacterial culture. Chest X-rays (CXR) were assessed for signs of TB and non-TB conditions. Diagnoses were categorized as confirmed PTB, clinically diagnosed PTB, or non-TB. Two-month follow-up assessed outcomes. Of 103 participants, 30 of 102 (29%) were HIV positive. Median age was 44 years (interquartile range 28-57). PTB was confirmed in 34 of 103 (33%), clinically diagnosed in 5 of 103 (5%), and not diagnosed in 62 of 103 (62%). In the non-TB group, CXR findings were consistent with bacterial pneumonia (24/62, 39%) or malignancy (12/62, 19%). At follow-up, 81 of 100 (81%) reported improvement, whereas 19 of 100 (19%) did not, including 12 of 100 (12%) deaths. HIV infection, smoking, alcohol use, rural residence, and lower SES were associated with death, no difference was seen by TB status. High 2-month mortality, regardless of final TB status, highlights the need for improved access to diagnostics and better treatment algorithms in severe respiratory illness. German Clinical Trials Register (DRKS00034074).

Age at First RSV Hospitalisation and the Risk of Subsequent Bacterial Pneumonia.

Design, synthesis, and optimization of Honokiol-Piperazine derivatives as lung-enriched agents against MRSA pneumonia infection.

Bacterial pneumonia is a common acute respiratory infection. The role of Meteorin-like (METRNL) in bacterial pneumonia is unknown. To investigate the clinical and functional role of METRNL in bacterial pneumonia. METRNL levels were examined in the animals and patients with bacterial pneumonia. Multiple genetic and pharmacologic approaches were used to investigate METRNL-mediated host immune responses during bacterial pneumonia. METRNL production was dramatically suppressed in response to acute bacterial lung infection. METRNL loss increased mortality and bacterial burden during Pseudomonas aeruginosa and Staphylococcus aureus pneumonia, but had no effects on Aspergillus fumigatus and influenza virus pnuemonia. Conversely, METRNL overexpression resulted in decreased mortality and bacterial burden from bacterial pneumonia. Furthermore, therapeutic administration of recombinant METRNL protein improved mortality and bacterial clearance in a neutrophil-dependent manner after bacterial pneumonia. METRNL enhanced bacterial phagocytosis and subsequent killing capacity of neutrophils, and conditional knockout of KIT receptor tyrosine kinase in neutrophils abolished METRNL-mediated protection against bacterial pneumonia. Furthermore, the increased antibacterial functions of neutrophils elicited by the METRNL-KIT axis was mediated through adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. The augmented antibacterial effects of METRNL on neutrophils were also confirmed in humans, and circulating METRNL levels were reduced in patients with bacterial pneumonia, which might serve as a new biomarker for patient stratification and therapeutic guidance. This study suggests that a potential theranostic approach involving METRNL-guided patient stratification and targeted therapy using METRNL rescue therapy may help improve the management of patients with bacterial pneumonia.

Pseudomonas aeruginosa is a major cause of acute nosocomial infections, as well as chronic respiratory infections associated with cystic fibrosis (CF). In chronic lung infections, P. aeruginosa populations typically exhibit extensive phenotypic variation, a trait linked to their need to undergo pathoadaptive mutations to counteract host-derived selective pressures. In this study, two clonally related P. aeruginosa isolates, SCPA07 and SCPA08, were identified to coexist in a single bronchoalveolar lavage fluid (BALF) sample from a patient with bacterial pneumonia. Whole-genome sequencing (WGS) was conducted to characterize their genetic background, as well as antimicrobial resistance and virulence gene profiles. A comprehensive analysis of phylogenetic relationships and comparative genomic features of the two isolates was conducted using a panel of bioinformatics tools. Their antimicrobial resistance mechanisms were elucidated via gene sequence analysis and quantitative reverse-transcription PCR (qRT-PCR). A series of phenotypic experiments, including growth, biofilm formation, environmental stress, and virulence assays, and others were performed to characterize their phenotypic traits. Antimicrobial susceptibility assay showed that both strains were carbapenem-non-susceptible (defined as intermediate or resistant according to the Clinical and Laboratory Standards Institute (CLSI) guidelines). Genomic analysis revealed that they are 'hypermutator' strains and harbor both the exoS and exoU virulence genes, indicating an increased propensity for persistent host infection and high virulence potential. Both strains harbored mutations in oprD, and exhibited elevated expression of AmpC β-lactamase and the efflux pump MexB, which most likely contributed to their non-susceptibility to carbapenems. Despite harboring nucleotide variations at only ten genetic loci, these two strains exhibited distinct phenotypic traits: SCPA07 showed rapid growth, strong biofilm formation, high virulence, and growth advantages under iron limitation and serum stress; in contrast, its variant SCPA08 had slow growth, poor motility, reduced pyocyanin production, low virulence, and increased tolerance to the host antimicrobials human cathelicidin LL-37 and hydrogen peroxide (H2O2). These phenotypic variations are proposed to be primarily driven by genetic mutations affecting the O-antigen biosynthesis, iron utilization, Porin D, and other determinants. This study elucidates the divergent adaptive evolutionary strategies of a single exoS+/exoU+ P. aeruginosa clone within the host during bacterial pneumonia, as well as their critical role in shaping the bacterium's virulence and adaptability, which sheds light on the within-host evolution dynamics of P. aeruginosa populations during their pathogenesis and persistence in the lung.

BACKGROUND Paragonimiasis, a food-borne parasitic zoonosis mainly caused by Paragonimus westermani and Paragonimus skrjabini in China, is rarely reported in Hangzhou, Zhejiang Province, a low-incidence urban setting. Paragonimiasis is often misdiagnosed due to its long incubation period, atypical manifestations, and low clinician awareness in non-endemic regions. Pleural effusion is common in thoracopulmonary paragonimiasis. We describe 2 imported, family-clustered pediatric cases (cousins) from endemic Zhaotong, Yunnan Province, both of whom presented with pleural effusion detected by chest computed tomography (CT); our report highlights clustered imported paragonimiasis in a low-incidence city. CASE REPORT Case 1: A 4-year-old boy was admitted with an 8-day history of fever and cough and was initially misdiagnosed with bacterial pneumonia (elevated leukocyte count, C-reactive protein levels, and loculated pleural effusion). Paragonimiasis was suspected based on eosinophilia and epidemiological exposure; it was confirmed by positive Paragonimus IgG test results. The patient recovered after treatment with oral praziquantel (PZQ). Case 2: The 9-year-old cousin of the patient in Case 1 displayed a persistent cough 1 month after the first case, with eosinophilia, right-sided pneumonia, and pleural effusion. Recognition of family clustering facilitated prompt diagnosis and successful treatment with PZQ. CONCLUSIONS This report highlights imported, family-clustered pediatric paragonimiasis in Hangzhou, a low-incidence city, providing greater diagnostic and epidemiological value than sporadic cases. Family clustering serves as a key clue for reducing misdiagnosis in non-endemic regions. Clinicians should consider paragonimiasis in children with relevant epidemiological exposure, unexplained pleural effusion, or eosinophilia, particularly when family clustering is present.

There is growing interest in the impact of internal body states on the brain and behavior. The detrimental effects of chronic lung inflammation on mental health are well recognized; however, underlying mechanisms are not known. Here, using a murine model of allergic asthma we report compromised fear extinction in mice with severe but not mild airway inflammation (AI); an effect abolished by anti-interleukin-17A (IL-17A) antibodies. Investigation of innate immune cells, microglia as-well-as transcriptomic signatures in the subfornical organ (SFO), a brain interoceptive node lacking a traditional blood-brain-barrier, revealed significant alterations in severe AI mice. IL-17 Receptor A (IL-17RA) was expressed in SFO microglia and upregulated in severe AI mice. Notably, ablation of microglial IL-17RA improved fear extinction in severe AI mice. Furthermore, we identified direct SFO projections to the infralimbic (IL) cortex, a key area regulating extinction. Importantly, chemogenetic inhibition of the SFO-IL circuit led to improved fear extinction in severe AI mice. Collectively, we report a unique body-to-brain interoceptive mechanism engaging the SFO microglia and an SFO-to-IL circuit, through which airway inflammatory mediators compromise fear extinction. Beyond asthma, our findings are relevant to other pulmonary pathologies (e.g. bacterial pneumonia, ARDS, COVID-19) highlighting a risk for cortical dysfunction and fear pathologies such as PTSD.

A juvenile bottlenose dolphin (Tursiops truncatus) was first observed among a group of approximately 12 dolphins on 10 December 2024, repeatedly breaching off Riverhead, Auckland, New Zealand. On subsequent observations, material consistent with fishing debris was seen entangled around the dorsal fin and tail flukes. While most conspecifics departed the area, a larger dolphin remained in close association with the entangled individual. The pair remained within the local area for at least 29 days prior to human intervention efforts to disentangle the animal. During the interim period, the entangled dolphin exhibited progressive deterioration in body condition and reduced activity compared with the free-swimming conspecific. The animal was found dead shortly thereafter. Within 48 hours of death, post-mortem MRI and necropsy were conducted on the cadaver, which was scored as decomposition carcass code 1 (within rigor mortis). These identified an emaciated, sexually immature female bottlenose dolphin. Gross examination revealed severe, multifocal to coalescing lacerations and abrasions affecting the dorsal fin and caudal peduncle, with associated soft-tissue loss and irregular wound margins. Histologically, sections from the dorsal fin laceration showed evidence of severe, subacute to chronic, ulcerative necrosuppurative dermatitis with secondary bacterial infection. Pulmonary tissue samples revealed an acute, severe bacterial pneumonia characterised by neutrophilic infiltration and short bacilli. The liver and spleen showed findings of hepatitis and splenitis, suggestive of bacterial septicaemia. Swab isolates from these pooled tissues identified moderate growth of Erysipelothrix rhusiopathiae and Pseudomonas spp. Collectively, in vivo evidence and post-mortem gross and histopathological findings were consistent with poor body condition resulting from a progressive wasting disease primarily associated with chronic entanglement, leading to chronic active deep infectious necrosuppurative dermatitis and subsequent fatal bacterial septicaemia. Bacterial septicaemia. This case highlights the importance of timely intervention in entanglement events to reduce the risk of secondary complications, including impaired foraging, progressive loss of body condition, and infection. Based on post-mortem findings, death was consistent with bacterial septicaemia in the context of a deep skin lesion to the dorsal fin caused by fishing gear and its subsequent pathological effects. From an animal welfare perspective, the prolonged duration of entanglement, progressive debilitation, and evidence of systemic wasting disease support a period of substantial and sustained welfare compromise prior to death. This incident would be classified as high-intensity, long-duration suffering.

Voriconazole (VRCZ) is an effective treatment for pulmonary aspergillosis. Active infectious disease leads to a reduction in cytochrome P450 activity, resulting in increased VRCZ concentrations. However, the impact of VRCZ dose reduction during the severe inflammatory state on VRCZ concentrations after the resolution of inflammation is not yet fully understood. Here, we report the time-course changes in VRCZ blood concentrations after inflammation in a patient with invasive pulmonary aspergillosis. A man in his 60s receiving oral VRCZ tablets at 400mg/day for invasive pulmonary aspergillosis developed marked inflammation due to bacterial pneumonia and influenza virus infection. C-reactive protein (CRP) levels increased to a peak of 35.54mg/dL, with a concomitant elevation in the VRCZ trough concentration to 4.7µg/mL. Following dose reduction to VRCZ 300mg/day, the trough concentration decreased to 1.1µg/mL on day 11 after dose reduction, while CRP declined to 4.78mg/dL after antibiotic therapy. VRCZ was continued at the same dose. However, four weeks after CRP levels had stabilized, the VRCZ concentration decreased to 0.6µg/mL. After re-escalation of VRCZ to 400mg/day, the trough concentration returned to the effective therapeutic range of 1.1µg/mL. After infection is controlled, VRCZ concentrations may decrease to levels below the therapeutic range. Following VRCZ dose reduction during a high inflammatory state, reassessment of trough concentrations after improvement of inflammation may be useful to prevent excessive decreases in VRCZ concentrations.

ABSTRACTA 49‐year‐old male presented with acute dyspnea and hydropneumothorax. Imaging and biopsy confirmed pleural tuberculosis. Despite atypical features and no risk factors, anti‐tuberculosis therapy led to rapid improvement. This case highlights the diagnostic challenge of distinguishing tuberculosis‐related hydropneumothorax from necrotizing bacterial pneumonia and empyema in the presence of complex radiological findings.

BackgroundCarbapenem-resistant gram-negative bacterial (CRGNB) pneumonia is a severe clinical challenge. This study aimed to assess the efficacy and safety of nebulized polymyxin B sulfate for its treatment.MethodsA multicenter, prospective, observational study was conducted in seven hospitals in Zhejiang Province, China, from January to October 2022. Patients diagnosed with CRGNB pneumonia and treated with nebulized polymyxin B sulfate were included. Data on baseline characteristics, microbiology, adverse events, and clinical outcomes were collected. The primary endpoint was the pathogen eradication rate 14 days after discontinuation of inhalation therapy. Secondary endpoints included microbial alternation, incidence of bronchospasm, and 28-day and 60-day mortality rates.ResultsA total of 91 patients with CRGNB pneumonia received nebulized polymyxin B sulfate. The duration of inhalation ranged from 7 to 15 days, with a median of 9 days. Concurrent intravenous polymyxin B was administered in 72.5% of patients. Among 87 patients with available microbiological data, pathogen eradication was achieved in 33 cases (37.9%) and presumed eradication in 30 cases (34.5%), resulting in a total eradication rate of 72.4%. Persistent CRGNB infection was observed in 24 patients (27.6%). Microbial alternation occurred in 26 patients (29.9%), mainly involving intrinsically polymyxin B-resistant species such as Burkholderia and Serratia spp., and 4 polymyxin B-resistant CRGNB strains (1 case of Acinetobacter baumannii, 2 cases of Klebsiella pneumoniae, and 1 case of Pseudomonas aeruginosa). The incidence of bronchospasm was 3.3% (3/91), all of which were relieved with inhaled corticosteroids and short-acting β2 agonists without discontinuation of inhalation therapy. The 28-day and 60-day mortality rates were 18.7% and 28.6%, respectively.ConclusionNebulized polymyxin B sulfate achieved a high pathogen eradication rate, low microbial alternation, and good airway tolerability in patients with CRGNB pneumonia; supporting its efficacy and safety as a therapeutic option.

ABSTRACT Butyrate-producing bacteria, which are components of the gut microbiome, activate host defense mechanisms against several types of infections, including respiratory viral infections. However, the clinical effectiveness of butyrate-producing Clostridium butyricum (CB)-containing probiotics in patients with coronavirus disease 2019 (COVID-19) remains unclear. We investigated the in-hospital mortality, period of mechanical ventilation, and incidence of secondary bacterial pneumonia in patients with COVID-19 from 2020 to 2021. The patients were divided into the probiotic (27) and non-probiotic (256) groups. The two groups did not show a significant difference in the SOFA scores (probiotic vs. non-probiotic, 2.1 ± 2.3 vs. 2.1 ± 2.9). Additionally, all patients received antiviral agents to treat COVID-19; however, the two groups did not show significant difference in their distribution. However, patients receiving CB preparations showed the shorter periods of mechanical ventilation (1.1 ± 2.5 days vs. 3.9 ± 9.4 days). Although not statistically significant, they also showed lower incidence of secondary bacterial pneumonia (7.4% vs. 15.6%) and the lower in-hospital mortality (3.7% vs. 15.2%) compared to the non-probiotic group. This retrospective clinical study revealed that the administrations of CB preparations might attenuate clinical symptoms related to COVID-19 and improve mortality. However, further clinical and basic studies are required to validate our findings.

Bacterial pneumonia is a significant global infectious disease due to its high contagion and mortality rates. In this study, the mucus-penetrable bimetallic composite nanoparticles (Cu-Mn NPs) with excellent lung-retention abilities and mucus-penetrating capabilities was developed by incorporating manganese dioxide into a copper-gallic acid complex and modifying it with PEGylated chitosan. Specifically, Cu-Mn NPs synergistically induce bacterial cuproptosis-like death, inhibit bacterial growth, eliminate drug-resistant biofilms, and promote macrophage polarization toward the M1 phenotype. In addition, the constructed Cu-Mn NPs could generate abundant reactive oxygen species, which disrupted bacterial membrane integrity, interfered with the respiratory chain, and significantly reduced bacterial virulence. More importantly, in a methicillin-resistant Staphylococcus aureus (MRSA)-infected pneumonia mouse model, treatment with Cu-Mn NPs significantly improved survival rates and reduced inflammatory injury without causing systemic toxicity. These findings show the considerable clinical potential of multifunctional Cu-Mn NPs for the targeted treatment of acute lung diseases associated with MRSA infection.

The overuse of antibiotics and the continuous evolution of drug-resistant bacteria present substantial obstacles to the clinical treatment of Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. This study reports the rational design of a bifunctional fusion polypeptide, S-thanatin (Ts)-functionalized elastin-like carrier (Ts-ELP), which integrates the antimicrobial peptide (AMP) Ts with a human-derived elastin‑like polypeptides (ELPs). This designer polypeptide serves as a smart carrier, capable of efficiently encapsulating the broad-spectrum antibiotic tigecycline (Tig) via reversible temperature-responsive phase transition hydrophobic interaction, resulting in a self-assembled, targeted nano-antibiotic, Tig@Ts-ELP (Tig@TsE). Comprehensive in vitro and in vivo evaluations demonstrate that Tig@TsE exhibits multiple advantageous features, including rapid and simple preparation, specific lipopolysaccharide (LPS)-targeting capability, excellent in vivo targeted delivery efficiency, and dual-responsive drug release triggered by the acidic pH and elevated matrix metalloproteinase-9 (MMP-9) levels in the CRKP-infected microenvironment, coupled with favorable biocompatibility. Moreover, the Ts peptide and Tig exhibit marked synergistic antibacterial effects against CRKP. This innovative nano-antibiotic delivery system is designed to increase local drug concentration at the infection site, boost bactericidal activity, and reduce systemic toxicity, thereby presenting a promising therapeutic strategy for the treatment of drug-resistant bacterial pneumonia.

A xanthene-based red-emitting fluorescent probe for the detection and monitoring of carbon monoxide in bacterial pneumonia models and in plant samples.

Coronavirus Disease 2019 (COVID-19) and other lower respiratory tract diseases (LRTDs), including bacterial pneumonia and acute respiratory distress syndrome, share overlapping clinical features but arise from distinct pathophysiological mechanisms. The molecular signatures that distinguish these diseases remain insufficiently characterized in African populations, where genetic background, endemic infections, and environmental exposures may substantially shape immune responses. We integrated spatially resolved single-cell transcriptomic profiles from lung autopsy specimens of 30 Malawian patients, including 10 with COVID-19, 12 with other LRTDs, and 8 non-LRTD controls. In total, 61,391 cells representing 15 cell types and 36,602 gene expression features were analyzed. Using an integrated machine learning framework that combined nine feature-ranking algorithms with incremental feature selection, we identified potential molecular signatures that could discriminate among disease states within this cohort. The optimal classification models achieved weighted F1 scores greater than 0.94, demonstrating a robust capacity to differentiate COVID-19 from other LRTDs in our dataset. Notably, the macrophage-associated state in COVID-19 was dominated by an IFN-γ response with upregulation of CD163 and HLA-DQA2, contrasting sharply with the type I/III interferon signature reported in European cohorts. In addition, we observed cell-type-specific COVID-19 signatures, including downregulation of CAV1 in AT1 cells, consistent with epithelial damage; dysregulation of SFTPC in AT2 cells, suggesting surfactant dysfunction; and upregulation of NFKBIA in neutrophils, indicating altered inflammatory regulation. Gene Ontology enrichment further revealed universal disruption of protein synthesis machinery, along with cell-type-specific alterations in immune activation, epithelial repair, and inflammatory signaling pathways.

Verification of the JRS adult pneumonia clinical practice guidelines 2024: Sensitivity and specificity of the mycoplasma pneumonia diagnostic prediction score.

Chronic pulmonary aspergillosis (CPA) affects those with underlying lung conditions or mild immunocompromise. Chronic pulmonary aspergillosis carries a poor prognosis in adults. Its pathogenesis remains obscure. We summarize all cases of CPA in children globally. From 6503 screened reports, we reviewed the full text of 604, of which 44 fit the inclusion criteria and an additional 11 other cases with little detail which were included under Supplementary Data. Chronic granulomatous disease and cystic fibrosis cases were excluded. We found 47 well-documented individual cases of CPA in children published from 1963 to 2022. Twenty-two cases were simple aspergillomas, and 11 were chronic cavitary pulmonary aspergillosis. Ages ranged from under 1 year to 17 years old, and 28 (59.8%) were male. Eighteen (38.3%) cases had no reported underlying disease. Underlying diseases included pulmonary tuberculosis (14.9%), Job's Syndrome (10.6%), congenital pulmonary airway malformation (8.5%), allergic bronchopulmonary aspergillosis or asthma (6.4%), pulmonary hydatid cyst (4.3%), bacterial pneumonia with cavitation (4.3%), diabetes mellitus (4.3%), and single cases of pulmonary sequestration or bronchogenic cyst. All cases had either microbiological or immunological evidence of Aspergillus spp. apart from 2 confirmed by histopathology only. Surgical resection only was done in 18 (39.1%) patients, 15 (32.6%) were treated with surgery and antifungal therapy, and 13 (28.3%) were only treated with antifungals; one patient died before intervention. Forty-three cases (91.5%) were alive on hospital discharge, but follow-up was limited, while 2 died. Chronic pulmonary aspergillosis is apparently rare in children but does occur, often with no antecedent condition. Prognosis is good with early diagnosis.

Abstract Rationale Bronchiectasis is the third most common airways disorder, after asthma and COPD. Global incidence and prevalence is increasing and is highest amongst females over age 65 years. Bronchiectasis epidemiology and outcomes suggest white female predominance when relying on disease-specific registries from Western countries. Air pollution and particulate matter have been suggested to trigger bronchiectasis exacerbations; however, the impact of deployment-related airborne exposures from contemporary conflicts on pulmonary outcomes is just beginning to be characterized. We compared bronchiectasis prevalence and outcomes for Veterans across a national cohort. Methods We included Veterans engaged with primary care at any VA outpatient facility between fiscal years 16-23 who had ICD-10 codes for bronchiectasis (J47.9). Demographics, smoking history (never, ever, current), body mass index (BMI) at baseline and comorbidities were determined using established data sources. Self-identified race/ethnicity was categorized as white and non-white (combined black, Hispanic Asian/Pacific Islander, Native American, mixed, and unknown). We compared sex differences in smoking and comorbid conditions including alcohol use disorder, COPD, cancer and immunodeficiencies. Chronic severity of illness was measured using Charlson comorbidity Index (CCI) and categorized as 0-1 vs. 2 vs. 3 or more. Our primary outcome was 1-year mortality by sex using logistic regression and adjusting for relevant confounders. Results We identified 1186 female and 17,465 male patients diagnosed with bronchiectasis (Table 1). Females were diagnosed at a younger age when compared to men (mean 63.6 versus 72.7 years). Non-white race was reported for 31.5% of patients and was more common among female patients (41.1% vs. male=30.8%). CCI scores varied by sex with females having lower CCI scores (female 0-1=54.4%, 2=19.3%, 3 + =26.3%; male 0-1=34.3%, 2=18.1%, 3 + =47.5%). Among specific comorbidities of interest, COPD, bacterial pneumonia, alcohol use disorder and cancer were most common in both sexes. One-year mortality was 3.1% for females and 10.9% for males (p < 0.0001). Conclusion Bronchiectasis-related characteristics and outcomes vary between female and male patients in a Veteran cohort. Substantial differences in age and race for patients with bronchiectasis were identified. Nested case control studies could inform how sex differences and exposures could affect bronchiectasis prevalence and outcomes. Future work will compare time-series to examine how toxic exposures could influence bronchiectasis in veterans. This abstract is funded by: VA healthcare system

Pulmonary Complications of Biological Therapies in Inflammatory and Autoimmune Diseases.