Inflammatory protein expression in human subglottic stenosis tissue mirrors that in a murine model.

OBJECTIVES: We undertook to describe the genetic and protein composition of subglottic stenosis (SGS) by measuring an array of protein expression and messenger RNA levels within human SGS tissue. We also sought to compare this human array to cytokine expression from a murine model of SGS in order to confirm the effective translational nature of our animal model. METHODS: Human granulation tissue from 10 patients with early symptomatic SGS was compared to control bronchus. The expression levels of 24 different cytokines were measured by a Luminex protein assay and real-time polymerase chain reaction. RESULTS: The protein expression in human SGS mirrors that seen in murine SGS. Transforming growth factor ß1, interleukin 1ß, and matrix metalloproteinase 9 were markedly elevated in both human and mouse SGS tissues. The protein array showed a statistically significant elevation in the proinflammatory cytokines tumor necrosis factor α, interleukin 1, granulocyte macrophage colony-stimulating factor, and interferon γ. CONCLUSIONS: This is the first study, to our knowledge, to measure an array of protein expression within human SGS tissue. The expression profile suggests that symptomatic tracheal granulation tissue is mostly within the early inflammatory phase of wound healing and has only begun fibrotic and angiogenic remodeling. This study validates our murine model of SGS, and also helps to define the exact pathways of tissue injury, in the hope of leading to new treatments for this difficult condition.

Speaking legibly: Qualitative perceptions of altered voice among oral tongue cancer survivors.

OBJECTIVE: Treatment for oral tongue cancer poses unique challenges to restoring and maintaining personally acceptable, intelligible speech. METHODS: We report how oral tongue cancer survivors describe their speech after treatment in a qualitative descriptive approach using constant comparative technique to complete a focal analysis of interview data from a larger grounded theory study of oral tongue cancer survivorship. Interviews were completed with 16 tongue cancer survivors 3 months to 12 years postdiagnosis with stage I-IV disease and treated with surgery alone, surgery and radiotherapy, or chemo-radiation. All interview data from the main study were analyzed for themes describing perceptions of speech as oral tongue cancer survivors. RESULTS: Actual speech impairments varied among survivors. None experienced severe impairments that inhibited their daily lives. However, all expressed some level of concern about speech. Concerns about altered speech began when survivors heard their treatment plans and continued through to survivorship without being fully resolved. The overarching theme, maintaining a pattern and character of speech acceptable to the survivor, was termed "speaking legibly" using one survivor's vivid in vivo statement. Speaking legibly integrate the sub-themes of "fears of sounding unusual", "learning to talk again", "problems and adjustments", and "social impact". CONCLUSIONS: Clinical and scientific efforts to further understand and address concerns about speech, personal presentation, and identity among those diagnosed with oral tongue are important to improving care processes and patient-centered experience.

Living in limbo: Being diagnosed with oral tongue cancer.

OBJECTIVE: Oral tongue cancer presents clinical challenges to effective diagnosis that affect patient experience. Patient experience of the diagnostic process is poorly described, making opportunities for nursing intervention unclear. METHODS: We qualitatively describe, using constant comparative analysis, oral tongue cancer diagnosis using data from a larger grounded theory study of oral tongue cancer survivorship. Using constant comparative analysis - in keeping with the methodology of the main study - we analyzed 16 survivor interviews for themes explaining the patient experience of oral tongue cancer diagnosis. RESULTS: We termed the broader diagnostic process "living in limbo." This process includes the themes describing the peri-diagnostic process itself - "self-detected lesion," "lack of concern," "seeking help," "not a straightforward diagnosis," and "hearing the diagnosis." Entry into treatment concludes "Living in Limbo" and is described by the theme "worry and trust." CONCLUSIONS: Our findings are limited by retrospective interviews and participant homogeneity among other features. Future research with prospective designs and diverse groups of people at risk for and diagnosed with oral tongue cancer, as well as targeting those who have had negative biopsies with no eventual diagnosis of oral tongue cancer, will build on our findings. Further, study of patient experience in other sociocultural context and healthcare systems is needed to inform nursing science and practice. Finally, "living in limbo" suggests that clinician and public education about oral tongue cancer diagnosis is needed.

Pulse steroid therapy inhibits murine subglottic granulation.

OBJECTIVE: Using a functional model of airway granulation tissue in subglottic stenosis, we investigated changes in inflammatory markers within granulation tissue in response to intraperitoneal dexamethasone injections. Changes in inflammatory markers will allow us to identify potential targets for immunological therapy. STUDY DESIGN: Institutional Animal Care and Use Committee-approved animal study. SETTING: Philadelphia Veterans Administration Medical Center animal research facility. SUBJECTS AND METHODS: Laryngotracheal complexes of donor mice underwent direct airway injury and were transplanted into subcutaneous tissue of 19 recipient mice in 2 groups: steroid treated and untreated, with sample sizes of 10 and 9, respectively. The steroid-treated arm received intraperitoneal injection of dexamethasone for 3 weeks. Laryngotracheal complexes were then harvested, and granulation formation was measured. The messenger RNA (mRNA) expression of transforming growth factor (TGF)-ß(1) and interleukin (IL)-1 was quantified. RESULTS: At 3 weeks posttransplantation, there were statistically significant differences in observable granulation formation as well as mRNA expression of TGF-ß(1) and IL-1ß in all groups within the steroid treated arm as compared with the untreated arm. CONCLUSIONS: Systemic steroids have been used to prevent formation of granulation tissue and subglottic stenosis. However, the study of the immunologic markers and the corresponding changes with steroid treatment has not been well studied in animal models. Using a previously described novel murine model, we begin to delineate inflammatory markers that can be applied for potential therapeutic targets.