Factors associated with the change of antimicrobial prescription before and after the National Action Plan on Antimicrobial Resistance: Additional analysis of a nationwide survey conducted by the Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases.

BACKGROUND: A nationwide survey conducted by the Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases in 2020 provided insights into antimicrobial prescription practices among clinic doctors. This study aimed to investigate factors influencing changes in antimicrobial prescriptions post-implementation of the National Action Plan on Antimicrobial Resistance (NAPAR) and doctors' inclination to prescribe antimicrobials for common cold cases. METHODS: In September 2020, randomly selected questionnaires were distributed to 3000 community-based medical clinics in Japan. The primary objective was to assess the reduction in antimicrobial prescriptions post-NAPAR implementation. Multivariate linear regression analysis was employed to identify associated factors. RESULTS: Analysis of 632 responses (response rate: 21.1%) revealed determinants of decreased antimicrobial prescriptions, including familiarity with the Guide to Antimicrobial Stewardship (ß = 0.482, t = 3.177, p = 0.002) and awareness of NAPAR (ß = 0.270, t = 2.301, p = 0.022). CONCLUSION: Interventions such as the Guide to Antimicrobial Stewardship may have contributed to the reduction in antimicrobial prescriptions among Japanese physicians. However, targeted strategies are needed to address high-prescription groups. Enhancing awareness and education on appropriate antimicrobial use should be integral components of future initiatives to combat antimicrobial resistance effectively.

Ivacaftor for Chronic Obstructive Pulmonary Disease - Results from a Phase 2, Randomized Controlled Trial.

RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) exhibit acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. CFTR modulators may improve outcomes in patients with COPD, although recent data regarding magnitude of benefit have been inconclusive and effects on mucociliary clearance are unknown. We conducted a phase 2, randomized, double blind placebo control trial to determine safety and tolerability, and explore the potential mechanism of ivacaftor for the treatment of COPD. METHODS: We randomized 40 patients with moderate to severe COPD and symptoms of chronic bronchitis to ivacaftor (N=30) or placebo (N=10) 150mg BID for 12 weeks. Primary endpoints included evaluation of safety of ivacaftor and pharmacokinetics (PK). Secondary endpoints included measures of CFTR activity and clinical outcomes. RESULTS: Ivacaftor was safe and tolerable with similar rates of adverse events rates between groups. Most common adverse event was diarrhea in the ivacaftor group and acute COPD exacerbation in the placebo group. PK analysis found the mean area under the curve over 12 hours (AUC12) to be 72% of the previously reported AUC12 in cystic fibrosis (CF). Treatment with ivacaftor did not improve sweat chloride, whole lung mucociliary clearance, lung function or respiratory symptoms. CONCLUSION: Ivacaftor was safe and well tolerated, but did not improve measures of CFTR activity or mucus clearance. As serum concentrations achieved were lower than observed in CF at the same dose, and modulation of wild type CFTR differs from G551D, further dose determination studies are needed to better understand treatment efficacy of CFTR potentiators in COPD. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT03085485.

Clinical, Biological, and Radiological Findings and Management of Lower Respiratory Tract Infections in a Tertiary Hospital in Romania.

Background Lower respiratory tract infections (LRTIs) remain a significant concern in pediatrics due to their substantial burden among childhood diseases. Romania has recently attained the status of a high-income country. Even though the mortality rate from respiratory diseases has significantly declined from 24.1 per 100,000 individuals in 2000 to 5.3 per 100,000 in 2022, the rate remains notably higher than the European average. Diagnosing LRTI is challenging due to its clinical similarity to noninfectious respiratory illness and frequent false-positive results or incidental findings on microbiologic tests. This often leads to antimicrobial overuse and adverse outcomes. Additionally, antibiotic resistance poses a significant global public health threat. Patients and method We conducted a retrospective analysis of pediatric LRTI cases at a tertiary pediatric center in Romania to evaluate diagnostic testing, imaging use, etiology identification, and treatment approaches. Children under 18, admitted to the Emergency Clinical Hospital for Children in Cluj-Napoca during an eight-month peak respiratory season, were included. Data from electronic medical records were analyzed for demographics, symptoms, physical exams, laboratory data, presence of fever, etiology, treatment, and outcomes. Results In total, 222 children were included in this study, with a median age of 29 months. Among the participants, 58% were male. The average hospital stay was 11 days. The total number of cases was almost equally split between bronchiolitis and pneumonia, with lobar pneumonia accounting for 12% of the included patients. We found two statistically significant correlations between the presence of fever, intercostal retracting, and the subtype of LRTI. An inflammatory response defined as an elevated leucocyte count and elevated C-reactive protein (CRP) was more likely to appear in pneumonia cases than bronchiolitis. From a therapeutic point of view, the prescription of hydrocortisone was statistically linked to bronchiolitis, but its use did not shorten hospitalization time. Conclusion Policy interventions and targeted treatments can reduce LRTI incidence and improve outcomes. Based on our correlations between specific clinical traits and subtypes of LRTIs, the use of assessment scores in children helps predict severe illness and the need for hospitalization. Promoting hygiene, social distancing, and addressing socioeconomic factors are crucial. Larger sample sizes and advanced diagnostics are needed to refine treatment strategies further. Early antibiotic use in children has long-term health implications, including a higher risk of respiratory-caused premature death in adulthood. This emphasizes the need for improved diagnostic processes and specific etiological identification, with metagenomics showing promise in this area.

Molecular characteristic, evolution, and pathogenicity analysis of avian infectious bronchitis virus isolates associated with QX type in China.

Infectious bronchitis virus (IBV) is one of the major avian pathogens plaguing the global poultry industry. Although vaccination is the primary preventive measure for IBV infection, the emergence of virus variants with mutations and recombination has resulted in IBV circulating globally, presenting a challenge for IB control. Here, we isolated 3 IBV strains (CZ200515, CZ210840, and CZ211063) from suspected sick chickens vaccinated with IBV live attenuated vaccines (H120, 4/91, or QXL87). Phylogenetic analysis of the S1 gene sequence of the spike (S) revealed that the 3 isolates belonged to the QX-type (GI-19 lineage). Whole genome sequencing and recombination analysis indicated that CZ200515 and CZ210840 contained genetic material from 4/91 and Scyz3 (QX-type), possibly due to recombination between the circulating strain and the 4/91 vaccine strain, while no evidence of recombination was found in CZ211063. Pathogenicity analysis in 1-day-old specific pathogen-free (SPF) chickens demonstrated that all 3 isolates caused severe tissue damage and varying degrees of mortality. Virus cross-neutralization assay revealed decreased antigen relatedness between the isolates and the QX-type vaccine strain (QXL87). Amino acid sequence homology analysis of S1 revealed 5%-6.5% variances between the isolates and QXL87. Analysis of the S1 subunit structure revealed that mutations of amino acid residues in the hypervariable region (HVR) and the neutralizing epitope region resulted in antigenic variation in isolates by changing the antigen conformation. Our data indicate antigenicity variances between QX isolates and QXL87 vaccine strains, potentially resulting in immune evasion occurrences. Overall, these results offer crucial insights into the epidemiology and pathogenicity of QX-type IBV, facilitating improved selection and formulation of vaccines for disease management.

Influence of acclimatization time on barometric whole-body plethysmography in cats with lower airway disease.

BACKGROUND: Barometric whole-body plethysmography (BWBP) is used as a noninvasive method to assess lung function in cats with lower airway disease (LAD). The duration of the acclimatization period in the measuring chamber varies between the studies. OBJECTIVES: To assess the influence of acclimatization time on variables indicative of lung function. ANIMALS: Twenty-four client-owned cats with LAD and 8 healthy cats. METHODS: In the prospective case-control study for each cat, a 30-minute dataset was collected. Data for the three 10-minute periods were statistically compared. RESULTS: The variables pause (T1 median: 0.8, range: [0.7-1]; T3: 0.9 [0.8-1.1]; P ≤ .01), peak inspiratory flow (PIF; T1: 84.9 [71.6-112.7]; T3: 75 [63.6-108.3]; P ≤ .001), peak expiratory flow (PEF; T1: 53.2 [41.5-76.6]; T3: 42.5 [34.6-57.8]; P ≤ .01), and a quotient of PEF and expiratory flow at 50% expired volume (PEF/EF50; T1: 1.2 [1.1-1.4]; T3: 1.2 [1.1-1.5]; P ≤ .01) varied significantly between first and third time period in cats with LAD. In healthy cats PIF (T1: 76.4 [66.3-85.2]; T2: 69.5 [58.3-85.2]; P ≤ .01), PEF (T1: 40 [32.8-58.6]; T2: 34.3, [29.8-44.6]; P ≤ .01), and PEF/EF50 (T1: 13.1 [11.6-14.6]; T3: 13.6 [12.4-16.3]; P ≤ .01) changed significantly between first and second time period. Enhanced pause did not change significantly in either group. CONCLUSIONS AND CLINICAL IMPORTANCE: Acclimatization time has a significant influence on multiple variables in BWBP. Manual correction of the data for tidal breathing flow-volume loop might be necessary.

Immuno-pathogenesis study of local infectious bronchitis virus G1-1 lineage variant showed altered tissue tropism in experimental broiler chickens.

Infectious bronchitis (IB) is an acute contagious disease of poultry caused by infectious bronchitis virus (IBV). This study investigated the immunopathogenesis and tissue tropism of an Indian IBV field isolate (IBV/Chicken/India/IVRI/Rajasthan/01/2023) in experimental broiler chickens. This isolate belongs to the G1-1 lineage and is closely associated with the Mass genotype. 106.23 EID50/0.2 mL of the virus was administered intranasally and intraocularly to the IBV-challenge group, whereas uninoculated allantoic fluid was administered to the control group. Clinical signs, gross and histopathological lesions, immunohistochemistry (IHC), viral load, humoral responses, and the relative expression of immune response genes were evaluated at seven observation points. The infected group showed a significant reduction in weight gain from 3 dpi onwards, with clinical signs of varying severity from 3 to - 11 dpi. Gross lesions and microscopic changes were observed in the nasal turbinates, trachea, lungs, and kidneys, mainly representing epithelial degeneration and necrosis with mononuclear infiltrates. The caecal tonsils also showed microscopic lesions at 7-9 dpi. Absolute viral load estimation in the organs corroborated the lesion severity scores and IHC results. The expression of innate immune responses broadly demonstrated higher expression in the trachea and lungs of the IBV-infected group during the early phase of infection, whereas similar responses were observed in the kidneys and caecal tonsils during the later phases of infection. This study suggests that the given IBV isolate may cause significant production losses in broilers and exhibit tissue tropism for both respiratory and non-respiratory tissues, triggering varying innate and adaptive immune responses.

The effect of nebulized N-acetylcysteine on the phlegm of chronic obstructive pulmonary disease: the NEWEST study.

BACKGROUND: Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. METHODS: This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score. RESULTS: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported. CONCLUSION: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks.

Viral respiratory infections requiring hospitalization in early childhood related to subsequent asthma onset and exacerbation risks.

Viral lower respiratory tract infections (LRTIs), including rhinovirus and respiratory syncytial virus during early childhood, have been linked to subsequent asthma. However, the impact of other respiratory viruses remains unclear. We analyzed nationwide Korean data from January 1, 2008, to December 31, 2018, utilizing the national health insurance database. Our study focused on 19 169 meticulously selected children exposed to severe respiratory infections requiring hospitalization with documented viral pathogens, matched with 191 690 unexposed children at a ratio of 1:10 using incidence density sampling. Our findings demonstrate that asthma exacerbation rates were higher among the exposed cohort than the unexposed cohort over a mean follow-up of 7.8 years. We observed elevated risks of asthma exacerbation and newly developed asthma compared to the unexposed cohort. Hospitalization due to rhinovirus, respiratory syncytial virus, influenza, metapneumovirus, and adenovirus was related to increased asthma exacerbations. Notably, we found a stronger association in cases of multiple LRTI hospitalizations. In conclusion, our study shows that early childhood respiratory viral infections are related to subsequent asthma exacerbations and new asthma diagnoses.

Isolation of a more aggressive GVI-1 genotype strain HX of the avian infectious bronchitis virus.

The avian infectious bronchitis virus (IBV) poses a significant economic threat to the global poultry industry. Although in recent years, the GVI-1 lineage of IBV has proliferated throughout China, there is still a lack of comprehensive studies regarding the pathogenicity of this lineage, particularly with respect to infections of the digestive tract and the antigenic characteristics of the S1 gene. In this study, we investigated the effects of infecting 14-day-old chicks with the HX strain of the GVI-1 lineage over a 14-d period postinfection. Assessment of the pathogenicity of the HX strain included clinical observations; monitoring of body weight, organ viral load, viral shedding, and gross anatomy; histopathological analysis, and bioinformatics-based antigenic characterization of the S1 protein. The findings revealed that compared with previously reported GVI-1 lineage strains, the HX strain is characterized by greater virulence, with infection leading to approximately 26% mortality and extensive severe organ damage, including that of the proventriculus and kidneys. Moreover, at 14 d postinfection, 80% of oral swabs and 100% of cloacal swabs from chickens infected with the HX strain tested positive, indicating a prolonged period of viral shedding relative to that previously reported for GVI-1 lineage strains. Bioinformatic analysis of B-cell epitopes on the S1 protein revealed 7 potential antigenic epitopes. Collectively, our findings in this study provide clear evidence to indicate that compared previously reported GVI-1 lineage strains, chicks infected with the IBV GVI-1 lineage strain HX are characterized by heightened rates of mortality, more pronounced organ damage, and an extended period of viral shedding. This comprehensive characterization highlights the pathogenic potential of the GVI-1 lineage and its capacity to induce severe kidney and proventriculus damage, thereby emphasizing the imperative of early initiated preventive measures. Furthermore, on the basis of our analysis of the antigenic properties of the S1 protein, we have identified 7 potential linear B-cell epitopes, which will provide valuable insights for the development of epitope-based vaccines.

Increased viperin expression induced by avian infectious bronchitis virus inhibits viral replication by restricting cholesterol synthesis: an in vitro study.

With the emergence of new variant strains resulting from high mutation rates and genome recombination, avian infectious bronchitis virus (IBV) has caused significant economic losses to the poultry industry worldwide. Little is known about the underlying mechanisms of IBV-host interactions, particularly how IBV utilizes host metabolic pathways for efficient viral replication and transmission. In the present study, the effects of the cell membrane, viral envelope membrane, and viperin-mediated cholesterol synthesis on IBV replication were explored. Our results revealed significant increase in cholesterol levels and the expression of viperin after IBV infection. Acute cholesterol depletion in the cell membrane and viral envelope membrane by treating cells with methyl-ß-cyclodextrin (MßCD) obviously inhibited IBV replication; thereafter, replenishment of the cell membrane with cholesterol successfully restored viral replication, and direct addition of exogenous cholesterol to the cell membrane significantly promoted IBV infection during the early stages of infection. In addition, overexpression of viperin effectively suppressed cholesterol synthesis, as well as IBV replication, whereas knockdown of viperin (gene silencing with siRNA targeting viperin, siViperin) significantly increased IBV replication and cholesterol levels, whereas supplementation with exogenous cholesterol to viperin-transfected cells markedly restored viral replication. In conclusion, the increase in viperin induced by IBV infection plays an important role in IBV replication by affecting cholesterol production, providing a theoretical basis for understanding the pathogenesis of IBV and discovering new potential antiviral targets.

Annual public health and economic burden of medically attended respiratory syncytial virus illnesses among US adults.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract disease (LRTD) among adults and can lead to serious morbidity and mortality; however, evidence on the magnitude of the public health and economic burden of adult RSV-LRTD is limited. This study was undertaken to project annual clinical outcomes and economic costs of medically attended RSV-LRTD among US adults, and to identify subgroups responsible for a disproportionate share of disease burden. METHODS: Clinical outcomes of RSV-LRTD were projected for subgroups of US adults defined by age and comorbidity profile (with vs. without chronic/immunocompromising medical conditions) based on corresponding population sizes, episode (disease) rates, and case-fatality rates. Economic costs comprised medical (i.e., direct) costs and non-medical (i.e., indirect) costs of RSV-LRTD, and were generated based on numbers of episodes and unit costs in relation to setting of care, age, and comorbidity profile. RESULTS: Among 265 million US adults aged ≥18 years in 2023, 6.5 million medically attended episodes of RSV-LRTD were projected to occur including 349,260 requiring hospitalization, 357,892 requiring an emergency department visit (not leading to hospitalization), and 5.8 million requiring other ambulatory care. Direct costs ($15.2 billion) and indirect costs ($9.7 billion) were projected to total $25.0 billion. Persons aged 60-99 years accounted for 31 % of the adult population and over 50 % of the economic burden of RSV-LRTD, while adults aged <60 years with chronic/immunocompromising medical conditions accounted for 10 % of the population and 27 % of the economic burden. CONCLUSIONS: Annual burden of RSV-LRTD among US adults-especially older adults and those of all ages with underlying medical conditions-is substantial. Preventive measures, such as recently approved RSV vaccines, have the potential to yield important improvements in public and patient health, and to reduce the economic burden of RSV-LRTD from the US healthcare system and societal perspectives.

Patent Foramen Ovale and Hypoxemia.

Although the most common clinical manifestations of a patent foramen ovale (PFO) are cryptogenic stroke and migraine with aura, PFO is also associated with platypnea-orthodeoxia syndrome, obstructive sleep apnea, and chronic obstructive pulmonary disease with hypoxemia out of proportion to the extent of pulmonary disease. This article will discuss these conditions and summarize the related literature.

Clinical approach for pulmonary lymphatic disorders.

In this editorial, we discuss the clinical implications of the article "Lymphatic plastic bronchitis and primary chylothorax: A study based on computed tomography lymphangiography" published by Li et al. Pulmonary lymphatic disorders involve abnormalities in the lymphatic tissues within the thoracic cavity. Specifically, pulmonary lymphatic perfusion syndrome describes a condition where the flow of lymphatic fluid in the lungs is redirected towards abnormally widened lymphatic vessels. Clinically, individuals with this syndrome may experience symptoms such as chyloptysis, plastic bronchitis (PB), chylothorax, chylopericardium, and interstitial lung disease. These disorders can be caused by various factors, including PB, chylothorax, and complex lymphatic malformations. Advancements in lymphatic imaging techniques, such as intranodal lymphangiography, computed tomography lymphangiography, and dynamic contrast-enhanced magnetic resonance lymphangiography, have enabled the detection of abnormal lymphatic flow. This has enhanced our understanding of the pathophysiology of these conditions. Additionally, innovative minimally invasive treatments, such as thoracic duct embolization, selective embolization of lymphatic channels, and surgical procedures aim to improve clinical condition of patients and address their dietary needs.

Detection and Molecular Characterization of GI-1 and GI-23 Avian Infectious Bronchitis Virus in Broilers Indicate the Emergence of New Genotypes in Bolivia.

Infectious Bronchitis Virus (IBV) is a major threat to the poultry industry worldwide, causing significant economic losses. While the virus's genetic structure is well understood, the specific strains circulating in Bolivia have remained uncharacterized until now. This study aimed to identify and characterize new IBV strains in Bolivia. Tissue samples from broilers exhibiting clinical signs of Infectious Bronchitis were screened to detect IBV using real-time RT-PCR (RT-qPCR). Positive samples with low cycle threshold (Ct) values were selected for sequencing the full S1 gene. Of the 12 samples analyzed, 10 were determined to be positive for IBV. However, only four samples yielded sufficient genetic material for sequencing and subsequent phylogenetic analysis. The results revealed the presence of GI-1 and GI-23 lineages, both belonging to genotype I (GI). The GI-1 lineage showed >99% sequence identity to the H120 and Massachusetts vaccine strains, suggesting a close relationship. In contrast, the GI-23 lineage clustered with other IBV strains, showing a distinct subclade that is genetically distant from Brazilian strains. No evidence of recombination was found. Furthermore, amino acid substitution analysis identified specific mutations in the S1 subunit, particularly in the hypervariable regions 1, 2, and 3. These mutations could potentially alter the virus's antigenicity, leading to reduced vaccine efficacy. The findings of this study highlight the importance of continued and broad genomic surveillance of circulating IBV strains and the need to improve vaccination strategies in Bolivia.

Exploring the mechanism of Lianhuaqingwen (LHQW) in treating chronic bronchitis based on network pharmacology and experimental validation.

BACKGROUND: Lianhuaqingwen (LHQW) has been used in the treatment of chronic bronchitis, but the precise mechanism through which LHQW exhibits its anti-inflammatory effects in this context is not yet fully understood. The aim of this study was to investigate the active ingredients and signaling pathways responsible for LHQW's effectiveness in managing chronic bronchitis. METHODS: The research leveraged the TCMSP database to determine the active compounds and drug targets of LHQW. In parallel, the GeneCards, DrugBank, and PharmGkb databases were used to uncover targets pertinent to chronic bronchitis. To discern the potential mechanisms by which LHQW's active ingredients might treat chronic bronchitis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Network pharmacology facilitated the construction of a drug-active ingredient-disease target network, aiding in forecasting the core targets for chronic bronchitis treatment by LHQW. Subsequently, molecular docking techniques alongside in vitro experiments were applied to confirm the interactions between the active ingredients and the primary targets. RESULTS: A total of 157 active ingredients, 225 potential drug targets, and 594 bronchitis-related targets were derived from various databases. Following this, 76 potential gene targets were pinpointed by integrating drug and related targets. GO and KEGG enrichment analyses were employed to identify key pathways involved in LHQW's mechanism for treating chronic bronchitis. By constructing a protein-protein interaction (PPI) network for the 76 potential gene targets, four core targets (TNF, IL6, IFNG, and STAT3) were identified as primarily involved in responses to lipopolysaccharide, the TNF pathway, and the JAK-STAT pathway. Molecular docking results revealed a favorable affinity between multiple active ingredients of LHQW and the four core targets, suggesting that the therapeutic effects are mediated through the inhibition of inflammatory responses and signaling pathways. Interestingly, quercetin, an active ingredient of LHQW, was observed to bind to all four core targets simultaneously. Furthermore, cell experiment and western blot analysis indicated that both LHQW and quercetin exhibit anti-inflammatory effects by targeting the four core proteins and the JAK-STAT pathways. CONCLUSION: This research emphasizes the diverse active ingredients, targets, channels, and pathways of LHQW in the treatment of chronic bronchitis, providing important perspectives for the creation of novel therapeutic drugs and clinical uses.

Mechanism of Jizhi syrup's prevention and treatment of acute bronchitis based on LPS-iNOS inflammatory mediators' signalling.

ETHNOPHARMACOLOGICAL RELEVANCE: Jizhi syrup (JZTJ) is composed of eight medicinal herbs, including Houttuynia cordata, Fagopyrum dibotrys, Ilex chinensis, Ephedra sinica, Aster tataricus, Peucedanum praeruptorum, Citrus aurantium and Glycyrrhiza uralensis. It is mainly used for coughing caused by exogenous wind heat. Symptoms include fever, aversion to cold, chest and diaphragm tightness, cough and sore throat; and acute bronchitis and acute exacerbation of chronic bronchitis with the above symptoms. PURPOSE: This study aimed to preliminary analyse the chemical components in the liposoluble part of JZTJ, evaluate the anti-inflammatory effect of JZTJ by using six animal and cell models and predict the target and mechanism of acute bronchitis prevention and treatment with JZTJ. METHODS: The chemical components in the liposoluble fraction of JZTJ (extracted by cyclohexane) were quantitatively analysed using gas chromatography-mass spectrometry (GC-MS). Classic non-specific inflammation models and acute bronchitis models were established to systematically evaluate the anti-inflammatory effect of JZTJ. The anti-inflammatory intensity and characteristics of three doses of JZTJ were comprehensively compared on the basis of principal component analysis method at the cellular and overall animal levels. By using lipopolysaccharides (LPSs) as modelling factors, a RAW264.7 macrophage inflammatory response model and a rat acute bronchitis model were created to study the effect of JZTJ on the in-vitro and - vivo LPS-iNOS-inflammatory mediators' inflammatory signalling pathway to reveal the mechanism of acute bronchitis prevention and treatment by JZTJ at the levels of genes, proteins, and inflammatory mediators. RESULTS: Seventeen alkane and ester compounds were preliminarily qualitatively identified from the lipid soluble fraction of JZTJ: dibutyl phthalate, tetradecane, ridecane, n-hexadecanoic acid, pentadecane, n-decanoic acid, 2,6,10,14,18,22-tetracosahexaene, 2,6,10,15,19,23-hexamethyl-(all-E)-; phenol, 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methyl-; hexadecane. JZTJ has a significant inhibitory effect on acute non-specific inflammation, specifically inhibiting 'xylene-induced ear swelling in mice', 'acetic acid-induced increased permeability of abdominal capillaries in mice' and 'egg white-induced foot swelling in rats'. The above effects are most evident in high doses, followed by medium doses, whereas low doses have poorer or no effects. JZTJ can prevent and treat acute bronchitis induced by LPS in mice and rats, significantly improve the pathological changes in patchy interstitial and alveolar bleeding with excessive neutrophil infiltration and inhibit the release of inflammatory mediators by LPS-induced RAW264.7 macrophages. Its mechanism of action may be by downregulating the phosphorylation level of p-ERK1/2 protein, thereby inhibiting inducible nitric oxide synthase (iNOS) mRNA, tumour necrosis factor (TNF)-α mRNA and IL-1ß. The expression levels of genes, such as mRNA and IL-6 mRNA, thereby reducing iNOS, TNF-α and IL-1ß. The expression of proteins in the cytoplasm of lung and bronchial tissue cells reduced the release of downstream inflammatory mediators NO and IL-6. CONCLUSION: Preliminary analysis of the chemical components in the lipid soluble fraction of JZTJ can lay the foundation for subsequent research on its effective components. Evaluating the anti-inflammatory effect of JZTJ is helpful for further research on its mechanism of action. The anti-inflammatory effects are exerted by regulating the inflammatory signalling pathway of LPS-iNOS inflammatory mediators, providing a scientific basis for their clinical application.

Respiratory Status in Children and Exposure to Animal Allergens-The Problem of Reverse Causality in Cross-Sectional Studies.

BACKGROUND: Some epidemiological studies suggest that early exposure to animal allergens during infancy reduces the risk of bronchial asthma in school-age children. However, the observed associations in some cases may be an effect of the study used (epidemiological observational studies, especially a cross-sectional study) and indicate reverse causality. AIM: This study aimed to determine the association between exposure to animal allergens and the prevalence of respiratory diseases, including bronchial asthma, considering the potential impact of reverse causality on the observed relationships. MATERIAL AND METHODS: An analysis of data from a cross-sectional epidemiological study conducted in 2020 involving 3237 primary school students aged 7-15 years in the Silesian Province (Southern Poland) was carried out. The parents of students completed a questionnaire based on The International Study on Asthma and Allergies in Childhood (ISAAC). The relationship between the occurrence of chronic cough, wheezing, and dyspnea in the last 12 months, night waking due to dyspnea, and asthma in the presence of pets was assessed. Exposure to animal allergens was determined by answering the question, "Are there any furry or feathered animals in the home?" with three response options: "yes; they have been in the past; no" (Scenario 1). For the analyses and to reveal a potential reverse causality effect, the last two response categories regarding pet ownership were combined to form a "no" category in Scenario 2, and the first two answers were combined into a "yes" category in Scenario 3. A chi-square test was used to assess the relationship between variables, and a statistical significance level of p < 0.05 was adopted. RESULTS: Chronic cough affected 9.5% of children, wheezing in the last 12 months-9.2%, night waking due to dyspnea-5.8%, dyspnea in the last 12 months-4.8%, bronchial asthma-9.2%. Analysis considering the category of having or not having pets (yes vs. no) showed that bronchial asthma was statistically significantly more common in children who did not have pets at home (10.9% vs. 7.9%, p = 0.002). A similar situation was observed for wheezing in the past 12 months (10.7% vs. 8.1%; p = 0.01) and nocturnal awakening due to dyspnea (6.8% vs. 5.1%, p = 0.03). No statistically significant differences were observed for the other symptoms. Analysis by time of pet ownership (a. present; b. present but in the past; c. not present) highlighted similar relationships. Asthma (a. 7.7% vs. b. 13.4% vs. c. 7.7%; p = 0.004), wheezing in the past 12 months (a. 8.1% vs. b. 8.9% vs. c. 10.9%, p = 0.03) and night waking (a. 5.0% vs. b. 4.5% vs. c. 7.1%; p = 0.04) were more common in children without pets and those who had owned pets in the past. The highest proportion of children with asthma was in homes where pets were present in the past. CONCLUSIONS: Analyses indicating a relationship between a higher prevalence of asthma and some respiratory symptoms, and the absence of pets cannot be considered as a casual association. The analysis conducted did not reveal a reverse causality effect. The results of observational epidemiological studies, especially a cross-sectional study, should always be interpreted with caution, considering possible distortions and conclusions drawn.

Biofilm Production and Its Implications in Pediatrics.

Biofilms, aggregates of bacteria enclosed in a self-produced matrix, have been implicated in various pediatric respiratory infections, including acute otitis media (AOM), otitis media with effusion (OME), adenoiditis, protracted bacterial bronchitis, and pulmonary exacerbations in cystic fibrosis. These infections are prevalent in children and often associated with biofilm-producing pathogens, leading to recurrent and chronic conditions. Biofilms reduce antibiotic efficacy, contributing to treatment failure and disease persistence. This narrative review discusses biofilm production by respiratory pathogens such as Streptococcus pneumoniae, non-typeable Haemophilus influenzae, Pseudomonas aeruginosa, and Staphylococcus aureus. It examines their mechanisms of biofilm formation, antibiotic resistance, and the challenges they present in clinical treatment. Various antibiofilm strategies have shown promise in vitro and in animal studies, including the use of N-acetylcysteine, enzymes like dispersin B, and agents disrupting quorum sensing and biofilm matrix components. However, their clinical application, particularly in children, remains limited. Traditional treatments for biofilm-associated diseases have not significantly evolved, even with biofilm detection. The transition from experimental findings to clinical practice is complex and requires robust clinical trials and standardized biofilm detection protocols. Addressing biofilms in pediatric respiratory infections is crucial for improving treatment outcomes and managing recurrent and chronic diseases effectively.

Influenza Vaccination in Adults in the United States with COPD before and after the COVID-19 Pandemic (2017-2022): A Multi-Year Cross-Sectional Study.

There is limited literature regarding seasonal influenza vaccination (SIV) among those with a history of chronic obstructive pulmonary disease (HCOPD) prior to the COVID-19 pandemic, and no information on the topic assessing the years following the pandemic. This cross-sectional study used the Behavioral Risk Factor Surveillance Survey (BRFSS) data from the years 2017 to 2022 (n = 822,783 adults ages 50-79 years; 50.64% males). The exposure was a HCOPD, and the outcome was SIV within the past year. Weighted and adjusted logistic regression models were conducted overall and by the significant effect modifiers: smoking status, sex, and year. Having an HCOPD significantly increases the weighted adjusted odds (WAO) of SIV when compared to not having an HCOPD overall and by smoking status, sex, and year. For 2017 through 2022, among all current, former, and never smokers with an HCOPD, the WAO of SIV were: 1.36 (1.28, 1.45), 1.35 (1.27, 1.43), and 1.18 (1.09, 1.27), respectively. Among males with an HCOPD who were current, former, and never smokers, the WAO of SIV were: 1.35 (1.23, 1.48), 1.45 (1.33, 1.58), and 1.23 (1.05, 1.44), respectively. Among females with an HCOPD who were current, former, and never smokers, the WAO of SIV were: 1.31 (1.20, 1.43), 1.24 (1.15, 1.35), and 1.13 (1.04, 1.23), respectively. Study findings suggest males had significantly greater WAO ratios of receiving SIV than females in 2020 and 2022, during and after the COVID-19 pandemic. More specifically, males with an HCOPD who were former smokers had significantly greater WAOR of receiving SIV than females in 2020 and 2022. Understanding the potential barriers to SIV receipt by smoking status and sex, especially during a pandemic, and especially for individuals impacted by an HCOPD, is essential for better health interventions in times of a national crisis such as a pandemic. Additionally, SIV receipt is low among those with an HCOPD, and efforts should be made to improve this.