ABSTRACT
Hiatal hernia (HH) is associated with gastro-oesophageal reflux (GOR) and/or GOR disease and may contribute to idiopathic pulmonary fibrosis (IPF). We hypothesised that HH evaluated by computed tomography is more common in IPF than in asthma or chronic obstructive pulmonary disease (COPD), and correlates with abnormal GOR measured by pH probe testing. Rates of HH were compared in three cohorts, IPF (n=100), COPD (n=60) and asthma (n=24), and evaluated for inter-observer agreement. In IPF, symptoms and anti-reflux medications were correlated with diffusing capacity of the lung for carbon monoxide (D(L,CO)) and composite physiologic index (CPI). HH was correlated with pH probe testing in IPF patients (n=14). HH was higher in IPF (39%) than either COPD (13.3%, p=0.00009) or asthma (16.67%, p=0.0139). The HH inter-observer κ agreement was substantial in IPF (κ=0.78) and asthma (κ=0.86), and moderate in COPD (κ=0.42). In IPF, HH did not correlate with lung function, except in those on anti-reflux therapy, who had a better D(L,CO) (p<0.03) and CPI (p<0.04). HH correlated with GOR as measured by DeMeester scores (p<0.04). HH is more common in IPF than COPD or asthma. In an IPF cohort, HH correlated with higher DeMeester scores, confirming abnormal acid GOR. Presence of HH alone was not associated with decreased lung function.
Subject(s)
Hernia, Hiatal/diagnostic imaging , Hernia, Hiatal/epidemiology , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/epidemiology , Tomography, X-Ray Computed/statistics & numerical data , Adult , Aged , Asthma/diagnostic imaging , Asthma/epidemiology , Cohort Studies , Female , Gastroesophageal Reflux/diagnostic imaging , Gastroesophageal Reflux/epidemiology , Gastroesophageal Reflux/therapy , Humans , Hydrogen-Ion Concentration , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/epidemiology , Male , Manometry , Middle Aged , Observer Variation , Prevalence , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Pulmonary Disease, Chronic Obstructive/epidemiology , Retrospective Studies , Severity of Illness IndexABSTRACT
The large mucin CD43 is actively excluded from T cell/APC interaction sites, concentrating in a membrane domain distal to the site of TCR engagement. The cytoplasmic region of CD43 was necessary and sufficient for this antipodal movement. ERM cytoskeletal adaptor proteins colocalized with CD43 in this domain. An ERM dominant-negative mutant blocked the distal accumulation of CD43 and another known ERM binding protein, Rho-GDI. Inhibition of ERM function decreased the production of IL-2 and IFNgamma, without affecting PKC(theta) focusing or CD69 upregulation. These results indicate that ERM proteins organize a complex distal to the T cell/APC interaction site and provide evidence that full T cell activation may involve removal of inhibitory proteins from the immunological synapse.
