Severe acute exacerbations (AE) of idiopathic pulmonary fibrosis (IPF) are medically untreatable and often fatal within days. Recent evidence suggests autoantibodies may be involved in IPF progression. Autoantibody-mediated lung diseases are typically refractory to glucocorticoids and nonspecific medications, but frequently respond to focused autoantibody reduction treatments. We conducted a pilot trial to test the hypothesis that autoantibody-targeted therapies may also benefit AE-IPF patients.

METHODS: Eleven (11) critically-ill AE-IPF patients with no evidence of conventional autoimmune diseases were treated with therapeutic plasma exchanges (TPE) and rituximab, supplemented in later cases with intravenous immunoglobulin (IVIG). Plasma anti-epithelial (HEp-2) autoantibodies and matrix metalloproteinase-7 (MMP7) were evaluated by indirect immunofluorescence and ELISA, respectively. Outcomes among the trial subjects were compared to those of 20 historical control AE-IPF patients treated with conventional glucocorticoid therapy prior to this experimental trial. RESULTS: Nine (9) trial subjects (82%) had improvements of pulmonary gas exchange after treatment, compared to one (5%) historical control. Two of the three trial subjects who relapsed after only five TPE responded again with additional TPE. The three latest subjects who responded to an augmented regimen of nine TPE plus rituximab plus IVIG have had sustained responses without relapses after 96-to-237 days. Anti-HEp-2 autoantibodies were present in trial subjects prior to therapy, and were reduced by TPE among those who responded to treatment. Conversely, plasma MMP7 levels were not systematically affected by therapy nor correlated with clinical responses. One-year survival of trial subjects was 46+15% vs. 0% among historical controls. No serious adverse events were attributable to the experimental medications. CONCLUSION: This pilot trial indicates specific treatments that reduce autoantibodies might benefit some severely-ill AE-IPF patients. These findings have potential implications regarding mechanisms of IPF progression, and justify considerations for incremental trials of autoantibody-targeted therapies in AE-IPF patients.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01266317.

BACKGROUND: Asthma remains a major public health concern because of its high prevalence and the costs it generates. Near-fatal asthma (NFA) episodes represent the most severe forms of the disease after fatal asthma with significant variations in their incidence between different populations.
OBJECTIVE: To analyze the episodes of NFA over a period of 11 years in the hospital. METHODS: The authors retrospectively reviewed all admissions due to asthma exacerbation in the hospital between 2000 and 2010 for patients younger than 18 years.
RESULTS: The study included 400 NFA episodes of 285 patients (74% women; mean age 66 years). Of these patients, 228 (80%) had a single episode of NFA and 57 had more than 1 episode during the study period. The authors observed no clear upward or downward trend during the study period. Readmitted patients had more comorbidities, poorer lung function, more severe forms of asthma and more admissions in the year before the index admission. There was a mortality rate of 3.1%. More than 20% of patients were not given controller treatment and more than 40% of patients were not treated with inhaled corticosteroids (ICS). CONCLUSIONS: NFA episodes are still prevalent in the population of patients with asthma. Reasons for this could be related to improper management in the stable phase, as suggested by the low rate of patients treated with ICS. It also seems necessary to optimize patient management during hospitalization because stays appear prolonged in comparison with studies in other countries.

Conclusion: In conclusion, our findings revealed existence of clinical/trigger related phenotypes based on BMI, allergic status, control level and geographical region with more frequent respiratory dysfunction and/or adverse health outcomes in uncontrolled, obese and non‐allergic phenotypes. This article is protected by copyright. All rights reserved. (Source: The Clinical Respiratory Journal)

The objective of our meta-analysis is to update the evidence on the prognostic value of elevated troponin levels in patient with acute normotensive pulmonary embolism (PE). We did a systematic literature review of database, including Pubmed, EMBASE, and Cochrane. Studies were included if those were done on normotensive patients with acute PE and serum troponin assay was done. The primary end point was short term all cause mortality. The secondary end points were short term PE related mortality and serious adverse events. Elevated troponin levels were significantly associated with the increased risk for short term mortality (odds ratio [OR], 4.80; 95% CI, 3.25–7.08, I 2 = 54%), PE related mortality (OR, 3.80; 95% CI, 2.74–5.27, I 2 = 0%) and serious adverse events (OR, 3.65; 95% CI, 2.4...