ICOS protects against mortality from acute lung injury through activation of IL-5+ ILC2s.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing irreversible lung scarring and loss of pulmonary function. IPF Patients suffer from a high rate of pulmonary infections and acute exacerbations of disease that further contribute to pulmonary decline. Low expression of the inducible T-cell costimulatory molecule (ICOS) in peripheral blood mononuclear cells predicts decreased survival of IPF patients, but the mechanisms by which ICOS protects are unclear. Using a model of bleomycin-induced lung injury and fibrosis, we now demonstrate that ICOS expression enhances survival from lung injury rather than regulating fibrogenesis. Of ICOS-expressing cells, type 2 innate lymphocytes (ILC2s) are the first to respond to bleomycin-induced injury, and this expansion is ICOS dependent. Interestingly, a similar decrease in ICOS+ ILCs was found in lung tissue from IPF patients. Interleukin (IL)-5, produced primarily by ILC2s, was significantly reduced after lung injury in ICOS-/- mice, and strikingly, treatment with IL-5 protected both ICOS-/- and wild-type mice from mortality. These results imply that low ICOS expression and decreased lung ILC2s in IPF patients may contribute to poor recovery from infections and acute exacerbation and that IL-5 treatment may be a novel therapeutic strategy to overcome these defects and protect against lung injury.

Test-retest reliability and smallest detectable change of the Bristol Impact of Hypermobility (BIoH) questionnaire.

OBJECTIVE: The Bristol Impact of Hypermobility (BIoH) questionnaire is a patient-reported outcome measure developed in conjunction with adults with Joint Hypermobility Syndrome (JHS). It has demonstrated strong concurrent validity with the Short Form-36 (SF-36) physical component score but other psychometric properties have yet to be established. This study aimed to determine its test-retest reliability and smallest detectable change (SDC). DESIGN: A test-retest reliability study. SETTING: Participants were recruited from the Hypermobility Syndromes Association, a patient organisation in the United Kingdom. PATIENTS: Recruitment packs were sent to 1080 adults who had given permission to be contacted about research. MAIN OUTCOME MEASURES: BIoH and SF-36 questionnaires were administered at baseline and repeated two weeks later. An 11-point global rating of change scale (-5 to +5) was also administered at two weeks. Test-retest analysis and calculation of the SDC was conducted on 'stable' patients (defined as global rating of change -1 to +1). RESULTS: 462 responses were received. 233 patients reported a 'stable' condition and were included in analysis (95% women; mean (SD) age 44.5 (13.9) years; BIoH score 223.6 (54.0)). The BIoH questionnaire demonstrated excellent test-retest reliability (ICC 0.923, 95% CI 0.900-0.940). The SDC was 42 points (equivalent to 19% of the mean baseline score). The SF-36 physical and mental component scores demonstrated poorer test-retest reliability and larger SDCs (as a proportion of the mean baseline scores). CONCLUSION: The results provide further evidence of the potential of the BIoH questionnaire to underpin research and clinical practice for people with JHS.