Factor (F) VIII inhibitor development remains one of the most serious complications in the treatment of hemophilia A. Former and recent studies on inhibitor development revealed that patients with severe hemophilia A and positive inhibitor family history are at highest risk of developing an inhibitor. Comparison of recent inhibitor incidence studies on previously untreated patients indicate that the risk of inhibitor development under treatment with recombinant FVIII concentrates is comparable to the inhibitor incidence under FVIII substitution by plasma-derived concentrates. However, longer observation periods are necessary to draw final conclusions. Since inhibitor development may result in inefficacy of FVIII concentrates in the treatment of severe bleedings, the induction of immune tolerance (IT) is still of main concern. Various regimens to induce IT by application of FVIII concentrates have been conducted up to now. Success rate appears to be influenced by low to high responder status, number of exposure days before onset of treatment, and dosage of therapeutic regimen. Especially, discontinuation of IT therapy seems to be associated with failure of therapy. Taking into account available data on IT therapy, we recommend early onset of a high dosage regimen in high responder patients as soon as possible after inhibitor detection, as this is associated with higher success rate and shorter elimination time.
Research has shown that cold air exercise causes significant respiratory dysfunction, especially in female athletes. However, how female and male athletes respond to cold air exercise is not known. Thus, we aimed to compare acute respiratory responses (function, recovery and symptoms) in males and females after high-intensity cold air exercise. Eighteen (nine female) athletes completed two environmental chamber running trials at 0 °C and −20 °C (humidity 34 ± 5%) on different days in a randomized starting order. Spirometry was performed pre, 3, 6, 10, 15 and 20 min post. Respiratory symptoms were measured posttrial and heart rate and rating of perceived exertion were assessed during each trial. No significant differences in delta change (pre to post) were found at either temperature between sexes for FEV1, FVC, FEF50% and FEF25–75%. At −20 °C, FEV1 decreased similarly in both sexes (males: 7.5%, females: 6.3%) but not at 0 °C, p = 0.003. Postexertion respiratory function recovery and reported symptoms were not different between sexes at either temperature. These results indicate no sex-based differences in acute respiratory responses (function, recovery and symptoms) to cold air exercise. However, intense exercise at −20 °C is challenging to the respiratory system in both sexes and may lead to altered respiratory responses compared to mild winter conditions like 0 °C.
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