Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, interstitial lung disease, with few therapeutic options. IPF is characterized by pulmonary restriction, dyspnea, hypoxemia, exercise intolerance and poor quality of life (QOL). Objectives: We aimed to examine the effect of exercise training (ET) on clinical outcomes in IPF patients. Methods: A randomized controlled study included thirty-two IPF patients (aged 68 ± 8 years) who were allocated either to the ET group (n = 15), participating in a 12-week, twice-weekly 60-min supervised ET-based pulmonary rehabilitation program, or to a control group (n = 17) continuing with regular medical treatment alone. Cardiopulmonary exercise test, 6-min walking distance (6MWD) test, 30-second chair-stand test, pulmonary function tests, dyspnea and QOL were assessed at baseline and at the end of the 12-week intervention. Results: Significant differences were observed between the ET and the control groups in raw mean deltas (Δ = post- - pre-intervention): Δ6MWD, 81 m, p < 0.001; ΔV
Idiopathic pulmonary fibrosis is a progressive, fatal disease. This prospective, randomised, double-blind, multicentre, parallel-group, placebo-controlled phase II trial (NCT00903331) investigated the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis.Eligible subjects were adults with idiopathic pulmonary fibrosis of ,3 years duration and a histological pattern of usual interstitial pneumonia on surgical lung biopsy. The primary objective was to demonstrate that macitentan (10 mg once daily) positively affected forced vital capacity versus placebo.Using a centralised system, 178 subjects were randomised (2:1) to macitentan (n5119) or placebo (n559). The median change from baseline up to month 12 in forced vital capacity was -0.20 L in the macitentan arm and -0.20 L in the placebo arm. Overall, no differences between treatments were observed in pulmonary function tests or time to disease worsening or death. Median exposures to macitentan and placebo were 14.5 months and 15.0 months, respectively. Alanine and/or aspartate aminotransferase elevations over three times upper limit of normal arose in 3.4% of macitentan-treated subjects and 5.1% of placebo recipients.In conclusion, the primary objective was not met. Long-term exposure to macitentan was well tolerated with a similar, low incidence of elevated hepatic aminotransferases in each treatment group. @ERSpublications Long-term exposure to macitentan was well tolerated in IPF in a trial that did not meet its primary end-point
At 11-month follow-up, the 12-week ET program showed clinical outcomes were preserved at baseline levels with some maintenance of improvements in leg strength and QOL in the ET group. The control group showed a trend of deterioration in the outcomes. At 30 months, the 12-week ET program did not show benefits in prognosis although the study was underpowered to detect such differences. We suggest including ET as a long-term continued treatment and as a core component of pulmonary rehabilitation programs for IPF patients.
No abstract
Pulmonary calcification is a common asymptomatic finding, usually discovered on routine chest X-ray or at autopsy. Pulmonary calcifications are caused mainly by two mechanisms: the dystrophic form and the metastatic form (1). Despite the different aetiologies, the pulmonary function and clinical manifestations are quite similar in both forms. We present a review of the clinical and radiology findings of the different aspects of pulmonary calcifications according to its pathogenesis and its anatomic distribution: parenchymal, lymphe node and pleural.
Aims To assess the short‐term immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA vaccine in a population of heart transplant (HTx) recipients. A prospective single‐centre cohort study of HTx recipients who received a two‐dose SARS‐CoV‐2 mRNA vaccine (BNT162b2, Pfizer‐BioNTech). Methods and results Whole blood for anti‐spike IgG (S‐IgG) antibodies was drawn at days 21–26 and at days 35–40 after the first vaccine dose. Geometric mean titres (GMT) ≥50 AU/mL were interpreted positive. Included were 42 HTx recipients at a median age of 61 [interquartile range (IQR) 44–69] years. Median time from HTx to the first vaccine dose was 9.1 (IQR 2.6–14) years. Only 15% of HTx recipients demonstrated the presence of positive S‐IgG antibody titres in response to the first vaccine dose [GMT 90 (IQR 54–229) AU/mL]. Overall, 49% of HTx recipients induced S‐IgG antibodies in response to either the first or the full two‐dose vaccine schedule [GMT 426 (IQR 106–884) AU/mL]. Older age [68 (IQR 59–70) years vs. 46 (IQR 34–63) years, P = 0.034] and anti‐metabolite‐based immunosuppression protocols (89% vs. 44%, P = 0.011) were associated with low immunogenicity. Importantly, 36% of HTx recipients who were non‐responders to the first vaccine dose became S‐IgG seropositive in response to the second vaccine dose. Approximately a half of HTx recipients did not generate S‐IgG antibodies following SARS‐CoV‐2 two‐dose vaccine. Conclusions The generally achieved protection from SARS‐CoV‐2 mRNA vaccination should be regarded with caution in the population of HTx recipients. The possible benefit of additive vaccine should be further studied.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating infection caused by the JC virus. It is an emerging disease in transplant recipients; however, it remains poorly defined. Twenty-four cases of PML reported in the literature in transplant recipients were reviewed. Of the 24 cases, nine occurred in renal, six in bone marrow, four in liver, three in heart and two in lung transplant recipients. Median time to onset was 17 months; 71% occurred within 24 months of transplantation. PML tended to occur later in the kidney recipients (P=0.04). Seventy-five percent had subacute presentation; hemiparesis (50%), apathy (46%) and confusion (38%) were the most frequently presented features. Treatment included reduction of immunosuppression and chemotherapy, mainly cidofovir. Death occurred within 2.5 months of the onset of symptoms in 17 patients (71%). PML is a unique entity that should be considered in any transplant recipient with neurological symptoms. The outcome is usually fatal, although regression has been reported.
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