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The human upper respiratory tract (URT) offers a variety of niches for microbial colonization. Local microbial communities are shaped by the different characteristics of the specific location within the URT, but also by the interaction with both external and intrinsic factors, such as ageing, diseases, immune responses, olfactory function, and lifestyle habits such as smoking. We summarize here the current knowledge about the URT microbiome in health and disease, discuss methodological issues, and consider the potential of the nasal microbiome to be used for medical diagnostics and as a target for therapy.

Most directly transmitted infections require some form of close contact between infectious and susceptible hosts to spread. Often disease models assume contacts are equal and use mean field estimates of transmission probability for all interactions with infectious hosts. Such methods may inaccurately describe transmission when interactions differ substantially in their ability to cause infection. Understanding this variation in transmission risk may be critical to properly model and manage some infectious diseases. In this study, we investigate how varying exposure and transmission may be key to understanding disease dynamics in the threatened desert tortoise Gopherus agassizii. We created heterogeneity in Mycoplasma agassizii exposure (the putative bacterial agent of a respiratory disease) by varying the duration of interactions between naturally infected and uninfected captive desert tortoises. Using qPCR, we identified new infections and compared models of transmission probability as a function of contact duration and pathogen load. We then examined the contact patterns of a wild tortoise population using proximity loggers to identify heterogeneity in contact duration. The top‐ranked model predicting M. agassizii transmission included a dose term defined as the product of the number of days in proximity to an infected host and the infection level of that host. Models predicted low transmission probability for short interactions, unless the infectious host had a high load of M. agassizii: such hosts were predicted to transmit infection at higher rates with any amount of contact. We observed predominantly short‐lived interactions in a free‐ranging tortoise population and thus, expect transmission patterns in this population to vary considerably with the frequency and duration of high infection levels. Mean field models may misrepresent natural transmission patterns in this and other populations depending on the distribution of high‐risk contact and shedding events. Rapid outbreaks in generally solitary species may result from changes to their naturally low‐risk contact patterns or due to increases in the frequency of severe infections or super‐shedding events – population characteristics that should be further investigated to develop effective management strategies.

Allergic rhinitis is a very common disorder that affects people of all ages, peaking in the teenage years. It is frequently ignored, underdiagnosed, misdiagnosed, and mistreated, which not only is detrimental to health but also has societal costs. Although allergic rhinitis is not a serious illness, it is clinically relevant because it underlies many complications, is a major risk factor for poor asthma control, and affects quality of life and productivity at work or school. Management of allergic rhinitis is best when directed by guidelines. A diagnostic trial of a pharmacotherapeutic agent could be started in people with clinically identified allergic rhinitis; however, to confirm the diagnosis, specific IgE reactivity needs to be recorded. Documented IgE reactivity has the added benefit of guiding implementation of environmental controls, which could substantially ameliorate symptoms of allergic rhinitis and might prevent development of asthma, especially in an occupational setting. Many classes of drug are available, effective, and safe. In meta-analyses, intranasal corticosteroids are superior to other treatments, have a good safety profile, and treat all symptoms of allergic rhinitis effectively. First-generation antihistamines are associated with sedation, psychomotor retardation, and reduced academic performance. Only immunotherapy with individually targeted allergens has the potential to alter the natural history of allergic rhinitis. Patients' education is a vital component of treatment. Even with the best pharmacotherapy, one in five affected individuals remains highly symptomatic, and further research is needed in this area.

Human papillomavirus (HPV)–associated oropharyngeal squamous-cell carcinoma differs from oropharyngeal cancers caused by tobacco and other factors. In this study, patients with oropharyngeal cancer were treated with cisplatin plus radiation therapy; the 3-year rate of overall survival was 82.4% among patients with HPV-positive tumors and 57.1% among patients with HPV-negative tumors. HPV status is an independent prognostic factor for survival among patients with oropharyngeal squamous-cell carcinoma. Patients with oropharyngeal cancer were treated with cisplatin plus radiation therapy; the 3-year rate of overall survival was 82.4% among patients with HPV-positive tumors and 57.1% among patients with HPV-negative tumors. HPV status is an independent prognostic factor for survival among patients with oropharyngeal squamous-cell carcinoma. The majority of patients enrolled in therapeutic trials for squamous-cell carcinoma of the head and neck have oropharyngeal squamous-cell carcinoma, which in a subgroup of these patients is caused by infection with human papillomavirus (HPV). 1 This subgroup is defined by the presence of high-risk types of HPV in tumor cells, predominantly HPV type 16 (HPV-16). Expression of viral E6 and E7 oncoproteins that inactivate the tumor-suppressor proteins p53 and the retinoblastoma protein (pRb), respectively, is necessary for malignant behavior of these tumors. 2 Several retrospective case series have shown that among patients with oropharyngeal squamous-cell carcinoma, patients with HPV-positive tumors have . . .

Upper respiratory tract diseases are a major concern in sheep, causing economic losses and affecting animal welfare. Accurate diagnosis is crucial for effective treatment and prevention. This case-based study assessed the use of computed tomography for diagnosing these diseases in sheep. Thirty-three sheep showing clinical signs of one or more upper respiratory tract diseases underwent computed tomography scans, which were compared to clinical diagnoses and postmortem examinations. Results showed that clinical diagnosis matched the postmortem findings in 26 of 38 cases, while computed tomography diagnosis matched in 36 of 38 diagnosed conditions, demonstrating higher accuracy. Computed tomography provided detailed anatomical reconstructions of the respiratory tract, allowing precise detection of lesions, identification of their origin or content, and clear visualisation of surrounding structures. Despite limitations such as high costs, risks related to general anaesthesia, and radiation exposure, its accuracy makes it a valuable tool for managing these diseases. The creation of extensive databases on common diseases affecting sheep could improve the accessibility and effectiveness of computed tomography in veterinary clinics.

Background and Objectives: Flexible bronchoscopy is widely used for evaluating intrathoracic airway and pulmonary diseases. However, its diagnostic value in upper airway abnormalities, including those involving the larynx, pharynx, and proximal trachea, remains underexplored. We evaluated the diagnostic significance and effectiveness of bronchoscopy in assessing upper airway diseases, including those involving the larynx, based on real-world data. Materials and Methods: We conducted a retrospective observational study involving 2229 patients who underwent bronchoscopy between March 2019 and December 2023. Patients with abnormal upper airway findings during bronchoscopy were referred for further otolaryngological evaluation. Patients were categorized according to the experience of their bronchoscopist (with ≥100 procedures defining experienced). Abnormal findings were analyzed according to anatomical region (oral cavity, larynx, and vocal cords), disease status (benign vs. malignant), and patient demographics. Multivariate logistic regression was used to identify predictors of abnormal findings. Results: Among 2229 patients (mean age 65.4 years), 72 (3.2%) exhibited visible upper airway abnormalities. No significant differences were observed in the abnormality detection rates between experienced and inexperienced operators across all anatomical regions. However, the presence of malignant disease was significantly associated with a higher likelihood of detecting abnormalities (5.4% vs. 1.9%, p < 0.001). Multivariate analysis revealed that male sex (odds ratio [OR] 2.069, p = 0.017), age < 74 years (OR 2.404, p = 0.009), and malignancy (OR 3.030, p < 0.001) were independent predictors of abnormal findings. Conclusions: Flexible bronchoscopy can incidentally detect upper airway abnormalities, particularly in patients with malignancy, male sex, or younger age. These findings suggest that systematic inspection of the upper airway during bronchoscopy may offer additional diagnostic value, regardless of the operator’s experience. The integration of upper airway assessment into routine bronchoscopic practice may enhance the early detection of clinically significant lesions and improve comprehensive patient care.

Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization, respectively; however, the pathophysiology of CRS remains unclear. The importance of innate lymphoid cells in Th2-mediated inflammatory disease has not been clearly defined. The objective of this study was to investigate the role of the epithelial cell-derived cytokine IL-33 and IL-33-responsive innate lymphoid cells in the pathophysiology of CRS. Relative gene expression was evaluated using quantitative real-time polymerase chain reaction. Innate lymphoid cells in inflamed ethmoid sinus mucosa from patients with CRSsNP and CRSwNP were characterized using flow cytometry. Cytokine production from lymphoid cells isolated from inflamed mucosa of patients with CRS was examined using ELISA and intracellular cytokine staining. Elevated expression of ST2, the ligand-binding chain of the IL-33 receptor, was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP and healthy control subjects. An increased percentage of innate lymphoid cells was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP. ST2(+) innate lymphoid cells are a consistent source of IL-13 in response to IL-33 stimulation. Significant induction of IL-33 was observed in epithelial cells derived from patients with CRSwNP compared with patients with CRSsNP in response to stimulation with Aspergillus fumigatus extract. These data suggest a role for sinonasal epithelial cell-derived IL-33 and an IL-33-responsive innate lymphoid cell population in the pathophysiology of CRSwNP demonstrating the functional importance of innate lymphoid cells in Th2-mediated inflammatory disease.

Background: Human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) is associated with improved survival compared with HPV-negative disease. However, a minority of HPV-positive patients have poor prognosis. Currently, there is no generally accepted strategy for identifying these patients. Methods: We retrospectively analysed 270 consecutively treated OPSCC patients from three centres for effects of clinical, pathological, immunological, and molecular features on disease mortality. We used Cox regression to examine associations between factors and OPSCC death, and developed a prognostic model for 3-year mortality using logistic regression analysis. Results: Patients with HPV-positive tumours showed improved survival (hazard ratio (HR), 0.33 (0.21–0.53)). High levels of tumour-infiltrating lymphocytes (TILs) stratified HPV-positive patients into high-risk and low-risk groups (3-year survival; HPV-positive/TIL high =96%, HPV-positive/TIL low =59%). Survival of HPV-positive/TIL low patients did not differ from HPV-negative patients (HR, 1.01; P =0.98). We developed a prognostic model for HPV-positive tumours using a ‘training’ cohort from one centre; the combination of TIL levels, heavy smoking, and T-stage were significant (AUROC=0·87). This model was validated on patients from the other centres (detection rate 67%; false-positive rate 5.6%; AUROC=0·82). Interpretation: Our data suggest that an immune response, reflected by TIL levels in the primary tumour, has an important role in the improved survival seen in most HPV-positive patients, and is relevant for the clinical evaluation of HPV-positive OPSCC.

Background Varicellovirus felidalpha-1 (FHV-1, previously Felid alphaherpesvirus-1 ) is a significant cause of upper respiratory tract disease in feline populations. Cats infected with FHV-1 show clinical signs that vary in severity. This can be due to differences in host responses and virus strain virulence. Investigating the gene transcription profiles during infections using FHV-1 strains could inform our understanding of host and viral factors contributing to disease outcomes. This study characterised the transcriptomes of Crandell–Rees feline kidney (CRFK) cells infected with field or vaccine FHV-1 strains to better understand the host response during infection. Methods Crandell–Rees feline kidney cells were infected with either the FHV-1 F2 vaccine strain or the 384/75 field strain associated with severe disease. The transcriptomes were characterised using RNA-sequencing. To determine the host cellular transcription profile, the total transcripts were mapped to the cat genome and compared to uninfected cells. To characterise the viral transcription profile, the total reads were mapped to each FHV-1 strain. The differentially expressed host genes between infection strains were compared and further analysed using the PANTHER database to examine host pathway regulation. Results The findings in this study show the differential host gene expressions induced by FHV-1 compared to uninfected CRFK cells. Genes encoding histone proteins were upregulated, while genes involved in cell adhesion and migration processes were downregulated during infections with FHV-1. Comparative analysis between field and vaccine strains showed similarities and differences in host gene expressions. Notably, upregulated genes unique to the field strain were associated with regulatory proteins involved in the cell cycle, while downregulated host genes in field and vaccine strains showed distinct host gene and pathway expressions involved in immune activation. Conclusions This study demonstrates the host and viral gene expressions during FHV-1 infection shows the distinct host responses to field and vaccine strains using an in vitro model. These findings provide a foundation for future transcriptomic investigations in other cell types, including ex-vivo explants systems, to enhance our understanding of host and viral factors contributing to disease outcomes.

Background Antibiotic use in human and veterinary medicine is considered a main driver of antimicrobial resistance. Although guidelines to promote appropriate use of antimicrobials in veterinary patients have been developed, antibiotic overprescription is assumed to be a common problem. The goal of this study was to investigate antimicrobial use in cats in Switzerland with acute upper respiratory tract disease (aURTD), feline lower urinary tract disease (FLUTD) and abscesses, and to assess compliance of prescription with consensus guidelines. A total of 776 cases (aURTD, n  = 227; FLUTD, n  = 333; abscesses, n  = 216) presented to two university hospitals and 14 private veterinary practices in Switzerland during 2016 were retrospectively evaluated. Clinical history, diagnostic work-up and antimicrobial prescription (class, dosage, duration) were assessed. Results A total of 77% (aURTD), 60% (FLUTD) and 96% (abscesses) of the cases received antibiotic therapy; 13–24% received combination or serial therapy. The cats were treated for a median of 7 (abscesses) and 10 days (aURTD, FLUTD). Treatments with potentiated aminopenicillins (40–64%), third generation cephalosporins (25–28%), aminopenicillins (12–24%) and fluoroquinolones (3–13%) were most common. Prescriptions were judged in complete accordance with consensus guidelines in 22% (aURTD), 24% (FLUTD) and 17% (abscesses) of the cases. Antibiotics were prescribed although not indicated in 34% (aURTD), 14% (FLUTD) and 29% (abscesses) of the cases. The presence of lethargy, anorexia or fever in cats with aURTD, and the detection of bacteriuria in cats with FLUTD were significantly associated with antibiotic therapy. Although diagnostic work-up was significantly more common (aURTD: university hospitals, 58%; private practices, 1%; FLUTD: university hospitals, 92%; private practices, 27%) and the use of critically important antibiotics significantly less common at the university hospitals (aURTD, 10%; FLUTD, 14%) compared to private practices (aURTD, 38%; FLUTD, 54%), the frequency of antibiotic treatment was not different between the university hospitals and private practices. Conclusions Our results indicate that overprescription of antibiotics in cats in Switzerland is common and accordance with guidelines is poor. The study highlights the need to promote antimicrobial stewardship in small animal medicine.