RESUMO
BACKGROUND: Respiratory epithelium is a key defense against inhaled pathogens. Vitamin D3 (VD) has been suggested to modulate airway inflammation; however, its effect on innate airway defenses, the physical barrier, mucociliary apparatus, and cytokine release remains unclear. OBJECTIVE: To investigate the outcomes of VD application prior to challenge in an in vitro model of human sinonasal epithelium, through assessment of epithelial transepithelial resistance (TER), cilia beat frequency (CBF), and interleukin (IL)-6 release, and secondarily to determine whether topical VD is beneficial to patients with inflammatory sinonasal pathology. METHODS: Primary human sinonasal epithelial cells from patients with eosinophilic chronic rhinosinusitis (eCRS) and healthy controls were cultured in air-liquid interface (ALI). Well-differentiated cultures from each patient were pretreated for 24 hours with 4 different VD doses. Toxicity was quantified at 24 hours in unchallenged ALI by lactate dehydrogenase (LDH) assay. Innate responses were assessed by measuring TER and CBF before and up to 24 hours after house dust mite Dermatophagoides pteronyssinus challenge. IL-6 release was evaluated 24-hour postchallenge. RESULTS: Fifteen patients (53 ± 13.5 years, 60% females, 53% eCRS) representing 120 ALI wells were assessed. VD (0, 25, 50, 150 IU/mL) released less LDH than vehicle, indicating noncytotoxicity (0.15 ± 0.02; 0.15 ± 0.00; 0.14 ± 0.02; 0.11 ± 0.01 vs 0.17 ± 0.03, P = .004). VD increased TER for eCRS wells at 5 minutes (50 IU/mL: Δ6.76 ± 3.93 vs Δ3.87 ± 2.46, P = .04) and 24 hours (50 IU/mL: Δ0.88 ± 0.49 vs Δ0.40 ± 0.42, P = .02; 150 IU/mL: Δ1.06 ± 0.58 vs Δ0.47 ± 0.46, P = .01). CBF increased at 1 hour for eCRS wells (50 IU/mL: Δ0.62 ± 0.14 vs Δ0.41 ± 0.13, P = .001; 150 IU/ml: Δ0.60 ± 0.13 vs Δ0.38 ± 0.11, P < .001). IL-6 release was similar between normal and eCRS wells. CONCLUSION: Topical VD supplementation in eCRS patients may be beneficial for innate epithelial defenses. VD is noncytotoxic and does not adversely affect the physical barrier, mucociliary apparatus, or IL-6 release. Further studies should clarify its potential as a therapeutic agent.
Assuntos
Cílios/patologia , Eosinófilos/imunologia , Hipersensibilidade/terapia , Inflamação/terapia , Mucosa Nasal/patologia , Seios Paranasais/patologia , Mucosa Respiratória/patologia , Rinite/terapia , Sinusite/terapia , Vitamina D/farmacologia , Administração Tópica , Adulto , Idoso , Animais , Antígenos de Dermatophagoides/imunologia , Células Cultivadas , Doença Crônica , Feminino , Humanos , Imunomodulação , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Pyroglyphidae , Rinite/patologia , Sinusite/patologiaRESUMO
BACKGROUND: Exposure to London Plane Tree (Platanus) bioaerosols in Sydney, Australia has been anecdotally linked to respiratory irritation, rhinitis, and conjunctivitis. OBJECTIVE: To determine the relationships between Platanus bioaerosol exposure, allergic sensitization, and symptoms. METHODS: Sixty-four subjects with self-reported Platanus symptoms were recruited from inner-urban Sydney. Allergic sensitization was determined by skin prick test (SPT) to 13 allergens. Airborne concentrations of Platanus pollen, trichomes, and achene fibers, and other pollen and fungal spores, were measured over the spring and summer of 2006-2007. Subjects' allergic symptoms were monitored concurrently. The Halogen immunoassay (HIA) was used to measure subjects' immunoglobulin E (IgE) reactivity to collected bioaerosols. RESULTS: Platanus pollen constituted 76% of total pollen between July 2006 and April 2007. Airborne concentrations of Platanus pollen peaked from August until October. Non-Platanus pollen peaked from July to December. Elevated concentrations of trichomes and achene fibers occurred from September to December and August to October, respectively. As determined by SPT, 85.9% of subjects were sensitized, 65.6% to any pollen tested, 56.3% to Lolium perenne, and 23.4% to Platanus. Higher mean daily symptom scores were only associated with high counts of non-Platanus pollens. HIA analysis demonstrated IgE binding to Platanus pollen in all Platanus sensitized subjects. Personal nasal air sampling detected airborne trichomes that were capable of being inhaled. Platanus trichomes or achene fibers did not bind IgE from any subject. CONCLUSIONS: Platanus bioaerosols exist in high concentrations between August and November in inner-urban Sydney but were not associated with seasonal symptoms. Platanus trichomes are inhaled and may constitute a respiratory irritant. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCTXXXXX.