Breast compression and reported pain during mammographic screening.

INTRODUCTION: We aimed to investigate the association between breast compression and experienced pain during mammographic screening. METHODS: Using a questionnaire, we collected information on pain experienced during mammography from 1155 women screened in Akershus, February-March 2018, as a part of BreastScreen Norway. The questionnaire provided information on pain using a numeric rating scale (NRS, 0-10) and related factors. Data on compression force (Newton, N), pressure (kilopascal, kPa) and breast characteristics were extracted from the DICOM-header and a breast density software. Log-binomial regression was used to determine the relative risk (RR) of severe versus mild/moderate experienced pain associated with compression parameters, adjusting for breast characteristics and related factors. RESULTS: Mean score of experienced pain was 2.2, whereas 6% of the women reported severe pain (≥7) during the examination. High body mass index (BMI) (≥27.3 kg/m2) was associated with a higher RR of pain scores ≥7 (RR 1.86, 95%CI 1.02-3.36) compared to medium BMI (23.7-27.2 kg/m2). Low compression pressure (4.0-10.2 kPa) was associated with a higher RR of severe pain (RR 2.93, 95%CI 1.39-6.20), compared with medium compression pressure (10.3-13.5 kPa) after adjusting for contact area, age, compressed breast thickness, volumetric breast density and BMI. The risk of severe versus mild/moderate pain (≥7 versus <7) decreased by 2% with increasing compression force (RR 0.98, 95%CI 0.97-1.00). CONCLUSION: Women reported low levels of pain during mammography. Further knowledge about factors affecting experienced pain is needed to personalize the examination to the individual woman. IMPLICATIONS FOR PRACTICE: Pain in shoulder(s) and/or neck prior to screening should be considered by the radiographers in a practical screening setting. A compression force of 100-140 N and pressure of 10.3-13.5 kPa are acceptable with respect to reported pain during mammography.

IL-5 production by resident mucosal allergen-specific T cells in an explant model of allergic rhinitis.

BACKGROUND: Seasonal allergic rhinitis is a chronic inflammation in the nasal mucosa triggered by inhaled aeroallergens. The inflammatory reaction is controlled by allergen-specific T cells, but where and how these T cells become activated is not fully understood. OBJECTIVES: We wanted to determine whether allergen-specific T-helper (Th) 2 cells are residing in the nasal mucosa under steady-state conditions outside of the pollen season and, if so, whether these cells are activated locally in response to allergen challenge. METHODS: Mucosal biopsies from the lower turbinate were obtained out of season from patients with either birch- or grass-pollen-allergic rhinitis and from healthy controls. Cultured explant samples were challenged with relevant pollen extract or with a mix of overlapping 20-mer peptides derived from the sequence of the major birch allergen, Betula verrucosa (Bet v) 1. After 24 h, culture medium was harvested for multiplex cytokine and tryptase analysis. RESULTS: Significant amounts of interleukin (IL)-5 were secreted from resident cells in response to ex vivo allergen challenge in the allergic group only. No increase was observed for the other cytokines measured. Production of IL-5 in response to both extract and the Bet v1-derived peptide mix strongly suggested that T cells were a major source of IL-5. CONCLUSION: Our explant model indicated that local presentation of antigen to resident allergen-specific Th2 cells is the early event in the pathogenesis of allergic rhinitis. These findings identify possible cellular targets for anti-inflammatory treatment.

A role for CCL28-CCR3 in T-cell homing to the human upper airway mucosa.

Lymphocyte recruitment to peripheral tissues is fundamental for immune surveillance and homeostasis, but the chemokines and chemokine receptors responsible for tissue-specific homing of T cells to the upper airway mucosa have not been determined. To address this, we analyzed the chemokines expressed in the normal human nasal mucosa and found that CCL28 is preferentially expressed at a high level on the lumenal face of vascular endothelial cells in the mucosa. Analysis of the cognate chemokine receptors revealed that close to 50% of the CD4(+) T cells in the human nasal mucosa expressed the CCL28 receptor CCR3, whereas CCR3 was hardly detectable on T cells in the small intestine and skin. In the circulation, CCR3(+) T cells comprised a small subset that did not express homing receptors to the intestine or skin. Moreover, depletion of CCR3(+)CD4(+) T cells abrogated the proliferative response of human blood CD4(+) T cells against the opportunistic nasopharyngeal pathogen Haemophilus influenzae, indicating that the CCR3(+)CD4(+) T-cell subset in the circulation contains antigen specificities relevant for the upper airways. Together, these findings indicate that CCL28-CCR3 interactions are involved in the homeostatic trafficking of CD4(+) T cells to the upper airways.

Glucocorticosteroids inhibit mRNA expression for eotaxin, eotaxin-2, and monocyte-chemotactic protein-4 in human airway inflammation with eosinophilia.

How eosinophils are preferentially recruited to inflammatory sites remains elusive, but increasing evidence suggests that chemokines that bind to the CCR3 participate in this process. In this study, we investigated the transcript levels and chemotactic activity of CCR3-binding chemokines in nasal polyps, a disorder often showing prominent eosinophilia. We found that mRNA expression for eotaxin, eotaxin-2, and monocyte-chemotactic protein-4 was significantly increased in nasal polyps compared with turbinate mucosa from the same patients, or histologically normal nasal mucosa from control subjects. Interestingly, the novel CCR3-specific chemokine, eotaxin-2, showed the highest transcript levels. Consistent with these mRNA data, polyp tissue fluid exhibited strong chemotactic activity for eosinophils that was significantly inhibited by a blocking Ab against CCR3. When patients were treated systemically with glucocorticosteroids, the mRNA levels in the polyps were reduced to that found in turbinate mucosa for all chemokines. Together, these findings suggested an important role for CCR3-binding chemokines in eosinophil recruitment to nasal polyps. Such chemokines, therefore, most likely contribute significantly in the pathogenesis of eosinophil-related disorders; and the reduced chemokine expression observed after steroid treatment might reflect, at least in part, how steroids inhibit tissue accumulation of eosinophils.