Immunotherapy with intravesical bacillus Calmette-Guérin (BCG) is considered the most effective adjuvant to endoscopic resection of bladder urothelial carcinoma in the therapeutic management of non-muscle invasive (NMIBC) at intermediate and high risk of recurrence and progression (pTa - pT1 and high-grade carcinoma in situ, CIS). Despite its proven efficacy, this type of treatment can determine local and systemic side effects of moderate or severe gravity, with the histological diagnosis of epithelioid granulomas in different organs, even in the absence of microbiological positivity of BCG. The immunotherapy with BCG is usually well tolerated and the virulence of the attenuated BCG is very low in immuno-competent patients, although only 16% of patients are able to receive all the instillations of the maintenance period (3 years) of treatment provided by the protocols, precisely because of side effects. Minor side effects usually resolve within a few hours or days. They develop in 3-5% of patients and usually consist of local infectious complications. Manifestations of BCG dissemination, such as vascular and ocular complications, are much less common, while BCG-disseminated infections, with granulomatous pneumonia or hepatitis present, are quite rare, representing 0.5-2% of the complications recorded. We present the clinical case of granulomatous lung and possibly liver infection caused by BCG in a patient aged 56 years being treated for several weeks with intravesical BCG for NIMBC pT1 high grade associated with CIS.
Objective: This study analysed whether the persistence of both reversible airway obstruction (RAO) and elevated BE counts was associated to reduced asthma control and accelerated lung function decline in treated severe asthmatics. Methods: About 202 severe asthmatics were studied after 12-120 months of step-5 treatment associated to anti-IgE therapy. Following treatments, reversibility tests, after inhaling 400 mcg of Salbutamol, were performed. FEV 1 > 12% or ≤12% changes differentiated RAO+ from RAO− subjects. Blood eosinophil (BE) counts after treatment were considered. Results: Pre-/post-treatment bronchodilator FEV 1 % and ACT were lower (61% [50-71], 74.4% [62.5-83.7] and 20[18-22]), whereas BE were higher (380 cells/µl [170-590]) in RAO+ compared to RAO− subjects (77% [64-88], p = 0.0001, 81.8% [66.1-94.3], p = 0.0001, 21[18-23], p = 0.045 and 230 cells/µl [80-360], p = 0.003). A negative relationship between SABA-induced FEV 1 % changes and pre-bronchodilator FEV 1 % (β = −0.551%; p = 0.0001) and ACT (β = −0.059; p = 0.038) was found. Conversely, post-treatment BE levels were positively related (β = 145.565 cells/µl; p = 0.003) to FEV 1 > 12% increases. A rising trend of pre-/post-bronchodilator FEV 1 % in time was observed in RAO− subjects with BE < 300 cells/µl. Conversely, we highlighted significant declining tendencies of pre/post-bronchodilator FEV 1 % in RAO+ patients with BE > 300 cells/µl reaching lower values after more than 36 months of step-5 treatment (59.6% [39.9-72.1] vs 74[66.5-89.2] of RAO+ individuals with BE < 300 cells/µl [p = 0.026] and 81.6% [66.1-91.8] of RAO-subjects with BE > 300 cells/µl [p = 0.009]). Conclusion: Persistent SABA-induced FEV 1 > 12%, especially when associated to BE > 300 cells/ml, may be a marker of accelerated lung function decline in severe asthmatics despite maximal step-5 treatment. The highest bronchodilation associated to the lowest BE levels should be the main goal of asthma treatment to prevent such decline.
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