The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study

Abstract: Background: Ear, nose and throat involvement in granulomatosis with polyangiitis (GPA) is frequently the initial disease manifestation. Previous investigations have observed a higher prevalence of Staphylococcus aureus in patients with GPA, and chronic nasal carriage has been linked with an increased risk of disease relapse. In this cross-sectional study, we investigated changes in the nasal microbiota including a detailed analysis of Staphylococcus spp. by shotgun metagenomics in patients with active and inactive granulomatosis with polyangiitis (GPA). Shotgun metagenomic sequence data were also used to identify protein-encoding genes within the SEED database, and the abundance of proteins then correlated with the presence of bacterial species on an annotated heatmap. Results: The presence of S. aureus in the nose as assessed by culture was more frequently detected in patients with active GPA (66.7%) compared with inactive GPA (34.1%). Beta diversity analysis of nasal microbiota by bacterial 16S rRNA profiling revealed a different composition between GPA patients and healthy controls (P = 0.039). Beta diversity analysis of shotgun metagenomic sequence data for Staphylococcus spp. revealed a different composition between active GPA patients and healthy controls and disease controls (P = 0.0007 and P = 0.0023, respectively), and between healthy controls and inactive GPA patients and household controls (P = 0.0168 and P = 0.0168, respectively). Patients with active GPA had a higher abundance of S. aureus, mirroring the culture data, while healthy controls had a higher abundance of S. epidermidis. Staphylococcus pseudintermedius, generally assumed to be a pathogen of cats and dogs, showed an abundance of 13% among the Staphylococcus spp. in our cohort. During long-term follow-up of patients with inactive GPA at baseline, a higher S. aureus abundance was not associated with an increased relapse risk. Functional analyses identified ten SEED protein subsystems that differed between the groups. Most significant associations were related to chorismate synthesis and involved in the vitamin B12 pathway. Conclusion: Our data revealed a distinct dysbiosis of the nasal microbiota in GPA patients compared with disease and healthy controls. Metagenomic sequencing demonstrated that this dysbiosis in active GPA patients is manifested by increased abundance of S. aureus and a depletion of S. epidermidis, further demonstrating the antagonist relationships between these species. SEED functional protein subsystem analysis identified an association between the unique bacterial nasal microbiota clusters seen mainly in GPA patients and an elevated abundance of genes associated with chorismate synthesis and vitamin B12 pathways. Further studies are required to further elucidate the relationship between the biosynthesis genes and the associated bacterial species

ANCA-associated vasculitis.

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients

Unusual presentation of temporal bone involvement in Churg–Strauss syndrome

Martinez Del Pero M, Moffat D, Sudhoff H. Unusual presentation of temporal bone involvement in Churg–Strauss syndrome. The Journal of Laryngology & Otology. 2008;122(4):425-427.#### Objective: To present a case of a 60-year-old male with a history of sudden onset sensorineural hearing loss due to Churg–Strauss syndrome. #### Case report: The patient had a 20-year history of asthma and recurrent right otitis media and a nasal polypectomy four years prior to presenting with ear symptoms. Ear, nose and throat involvement is common in Churg–Strauss syndrome, usually manifesting as allergic rhinitis and chronic rhinosinusitis with or without polyps. #### Conclusions: Otolaryngologists play an important role in making an early diagnosis of this disease. To our knowledge this is the first case of Churg–Strauss syndrome primarily presenting with otological pathology: left sensorineural hearing loss and right otitis media

Pneumatisation of turbinates and paranasal sinuses in children: case report

Objective: To describe a rare case of multiple anatomical variations in the sinonasal skeleton of an adolescent with chronic rhinosinusitis, together with its successful surgical management. Case report: A 15-year-old male adolescent was referred with a 3-year history of nasal blockage and hyposmia. His symptoms did not improve on maximal medical therapy. A pre-operative computed tomography scan revealed numerous anatomical variations in his nose and paranasal sinuses. He underwent neuronavigation-assisted endoscopic sinus surgery without complication, and with subsequent resolution of his symptoms at 10 months. Conclusion: Chronic rhinosinusitis in children offers its own set of unique surgical challenges. The effectiveness and safety of sinus surgery in this population can be improved through the knowledge of anatomical variants, and is aided by the use of image guidance systems