Common airborne fungi induce species-specific effects on upper airway inflammatory and remodelling responses.

OBJECTIVE: Whilst the exact cause of chronic rhinosinusitis (CRS) remains elusive, it is clear that both inflammation and remodelling are key disease processes. Environmental fungi have been linked to airway inflammation in CRS; however, their role in the pathogenesis of this condition remains controversial. The current consensus suggests that whilst fungi may not be directly causative, it is likely that CRS patients have deficits in their innate and potentially acquired immunity, which in turn may modify their ability to react to fungi. This study used a nasal polyp explant tissue stimulation model to study the inflammatory and remodelling responses related to challenge with common airborne fungal species. METHODS: Ex vivo nasal polyp tissue from six well phenotyped CRSwNP patients undergoing functional endoscopic sinus surgery was stimulated with 1, 10 and 100 µg/ml of Alternaria alternata, Aspergillus niger, Cladosporium sphaerospermum and Penicillium notatum and compared with unchallenged polyp tissue as control. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of pro-inflammatory cytokines interleukin-6 (IL-6), granulocyte macrophage colony stimulating factor (GM-CSF) and tumour necrosis factor-α (TNF-α); and pro-remodelling cytokines transforming growth factor-b1 (TGF-b1), and basic fibroblast growth factor (bFGF) in the polyp supernatant. RESULTS: Aspergillus niger stimulation increased pro-inflammatory cytokines TNF-α, GM-CSF and IL-6 whilst having little effect on the remodelling cytokines bFGF and TGF-b1. In contrast, stimulation with Cladosporium sphaerospermum, Alternaria alternata and Penicillium notatum reduced pro-inflammatory cytokines TNF-α and IL-6, but induced a dose-dependent increase in remodelling cytokines TGF-b1 and bFGF. CONCLUSIONS: This study shows that common airborne fungi induce species-specific effects on the upper airway inflammatory and remodelling responses. These findings provide further immunological evidence of a disease-modifying role for fungi in CRS.

Treatment of breast adenocarcinoma metastasis to the neck: dedifferentiation of the tumor as suggested by hormone markers.

BACKGROUND: Breast carcinoma rarely metastasizes to the neck, and its management in this area is controversial. There is little published data about whether hormone receptor status changes between primary breast tumors and neck metastasis and whether this influences management. METHODS: We evaluated the demographics and treatment of 13 patients presenting with neck metastasis. We used immunochemistry to assess estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 in the primary and metastatic neck nodes. RESULTS: Hormone receptor status changed in some patients (23% for estrogen receptor, and 31% for progesterone receptor). Three patients had complete excision of their neck disease and subsequent good local control. None of our patients survived despite treatment. CONCLUSION: The change in hormone status could suggest tumor dedifferentiation. Surgical resection, where possible, achieves good local control for these patients, but, because survival is poor, it is only recommended when it results in little significant morbidity.