B-cell activation is increasingly linked to numerous fibrotic lung diseases, and it is well known that aggregates of lymphocytes form in the lung of many of these patients. Activation of B-cells by pattern recognition receptors (PRRs) drives the release of inflammatory cytokines, chemokines, and metalloproteases important in the pathophysiology of pulmonary fibrosis. However, the specific mechanisms of B-cell activation in patients with idiopathic pulmonary fibrosis (IPF) are poorly understood. Herein, we have demonstrated that B-cell activation by microbial antigens contributes to the inflammatory and profibrotic milieu seen in patients with IPF. B-cell stimulation by CpG and b-glucan via PRRs resulted in activation of mTOR-dependent and independent pathways. Moreover, we showed that the B-cell-secreted inflammatory milieu is specific to the inducing antigen and causes differential fibroblast migration and activation. B-cell responses to infectious agents and subsequent B-cell-mediated fibroblast activation are modifiable by antifibrotics, but each seems to exert a specific and different effect. These results suggest that, upon PRR activation by microbial antigens, B-cells can contribute to the inflammatory and fibrotic changes seen in patients with IPF, and antifibrotics are able to at least partially reverse these responses.
Study Objectives: Many patients struggle with adherence to positive airway pressure (PAP) therapy for sleep apnea. In this systematic review we examined the effect that patient-facing applications (PFA)-web-based applications that interact directly with the patient-have on PAP adherence. Methods: A comprehensive search of PubMed, CINAHL, MEDLINE, and SCOPUS databases was performed. We looked for studies where: (1) patients were adults with sleep apnea initiating PAP therapy for the first time; (2) the intervention was a PFA that incorporated individual PAP use data; (3) the comparison was usual and/or telemedicine care, and (4) outcomes of objective PAP adherence data were recorded. Results: Seven studies were identified (two randomized trials, one prospective cohort trial, four retrospective cohort studies). Cumulatively the studies enrolled 304,328 patients, with individual enrollment ranging between 61 and 172,678 patients. Six studies showed that PFA use was associated with using PAP for significantly more hours per night (range 0.7-1.3 hours more). PFA cohorts used PAP a greater proportion of nights and had a lower rate of mask leak. There was no difference in apnea-hypopnea index and self-reported measures of symptoms between study groups. Conclusions: PFA use was associated with improved adherence to PAP therapy. Although this conclusion is based on only two small trials and predominantly observational studies and therefore should be tested in large prospective trials, the PAFs are inexpensive, do not draw on health care resources, and show promise in improving PAP therapy for OSA.
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