Pneumocystis pneumonia(PCP) is a life-threatening infection in immunocompromised patients. It is relatively uncommon in patients with lung cancer. We report a case of PCP in a 59-year-old man with a past medical histo...Pneumocystis pneumonia(PCP) is a life-threatening infection in immunocompromised patients. It is relatively uncommon in patients with lung cancer. We report a case of PCP in a 59-year-old man with a past medical history of chronic obstructive pulmonary disease treated with formoterol and a moderate daily dose of inhaled budesonide. He had also advanced stage non-small lung cancer treated with concurrent chemo-radiation with a cisplatin-etoposide containing regimen. The diagnosis of PCP was suspected based on the context of rapidly increasing dyspnea, lymphopenia and the imaging findings. Polymerase chain reaction testing on an induced sputum specimen was positive for Pneumocystis jirovecii. The patient was treated with oral trimethoprim-sulfamethoxazole and systemic corticotherapy and had showed clinical and radiological improvement. Six months after the PCP diagnosis, he developed a malignant pleural effusion and expired on hospice care. Through this case, we remind the importance of screening for PCP in lung cancer patients under chemotherapeutic regimens and with increasing dyspnea. In addition, we alert to the fact that long-term inhaled corticosteroids may be a risk factor for PCP in patients with lung cancer. Despite intensive treatment, the mortality of PCP remains high, hence the importance of chemoprophylaxis should be considered.展开更多
It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein un...It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein unbound, and active ICS can cause systemic adverse effects. Therefore, a detailed investigation of drug-protein interaction could be of great interest to understand the pharmacokinetic behaviour of corticosteroids and for the design of new analogues with effective pharmacological properties. In the present work, the interaction between some corticosteroids and human serum albumin(HSA) has been studied by spectroscopic approaches. UV–Vis spectroscopy confirmed that all the investigated corticosteroids can bind to HSA forming a protein-drug complex. The intrinsic fluorescence of HSA was quenched by all the investigated drugs, which was rationalized in terms of a static quenching mechanism. The thermodynamic parameters determined by the Van't Hoff analysis of the binding constants(negative ΔH and ΔS values) clearly indicate thathydrogen bonds and van der Waals forces play a major role in the binding process between albumin and betamethasone, flunisolide and prednisolone, while hydrophobic forces may play a major role in stabilizing albumin-triamcinolone complexes.展开更多
Background:Inhaled corticosteroids (ICSs) for treating asthma are controversial because of their negative effects on the growth of asthmatic children and without clearly defined withdrawal strategy.A 2-year ICS step-d...Background:Inhaled corticosteroids (ICSs) for treating asthma are controversial because of their negative effects on the growth of asthmatic children and without clearly defined withdrawal strategy.A 2-year ICS step-down and withdrawal strategy has been developed for asthmatic children receiving 3-year subcutaneous immunotherapy (SCIT).Methods:Eleven children were included into the SCIT group and 13 children into the ICS group.ICSs were discontinued when children met the following criteria:requiring only 1 puff per day,with good control,for at least 6 months;having a forced expiratory volume in 1 second (FEV1)/forced vital capacity ≥80%;and SCIT discontinued for ≥24 months.The main endpoints were the results of both the childhood asthma control test (C-CAT) and the methacholine bronchial provocation test.Results:In the SCIT group,all the 11 children had ICS discontinued,with one child developed asthma attack after pneumonia and received ICS again after completion of SCIT.In the ICS group,five children discontinued ICS and developed asthma attacks later and received ICS again;the other eight children developed severe symptoms during ICS step-down.Thus,the discontinuation of ICS was only achieved in the SCIT group.The dose of methacholine that caused a decrease of 20% in FEV1 continued to improve after discontinuation of ICS for the SCIT group and presented better results than the ICS group (P=-0.050).After completion of SCIT,the C-CAT had improved significantly after 30 months of treatment compared with the ICS group (P<0.05).Conclusion:In the present study,we developed a 2-year step-down and withdrawal strategy from ICSs strategy for allergic asthma children receiving SCIT;the strategy was efficacious and safe.展开更多
文摘Pneumocystis pneumonia(PCP) is a life-threatening infection in immunocompromised patients. It is relatively uncommon in patients with lung cancer. We report a case of PCP in a 59-year-old man with a past medical history of chronic obstructive pulmonary disease treated with formoterol and a moderate daily dose of inhaled budesonide. He had also advanced stage non-small lung cancer treated with concurrent chemo-radiation with a cisplatin-etoposide containing regimen. The diagnosis of PCP was suspected based on the context of rapidly increasing dyspnea, lymphopenia and the imaging findings. Polymerase chain reaction testing on an induced sputum specimen was positive for Pneumocystis jirovecii. The patient was treated with oral trimethoprim-sulfamethoxazole and systemic corticotherapy and had showed clinical and radiological improvement. Six months after the PCP diagnosis, he developed a malignant pleural effusion and expired on hospice care. Through this case, we remind the importance of screening for PCP in lung cancer patients under chemotherapeutic regimens and with increasing dyspnea. In addition, we alert to the fact that long-term inhaled corticosteroids may be a risk factor for PCP in patients with lung cancer. Despite intensive treatment, the mortality of PCP remains high, hence the importance of chemoprophylaxis should be considered.
基金supported by a grant from the University of Torino(Ricerca Locale ex-60%,Bando 2015)
文摘It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein unbound, and active ICS can cause systemic adverse effects. Therefore, a detailed investigation of drug-protein interaction could be of great interest to understand the pharmacokinetic behaviour of corticosteroids and for the design of new analogues with effective pharmacological properties. In the present work, the interaction between some corticosteroids and human serum albumin(HSA) has been studied by spectroscopic approaches. UV–Vis spectroscopy confirmed that all the investigated corticosteroids can bind to HSA forming a protein-drug complex. The intrinsic fluorescence of HSA was quenched by all the investigated drugs, which was rationalized in terms of a static quenching mechanism. The thermodynamic parameters determined by the Van't Hoff analysis of the binding constants(negative ΔH and ΔS values) clearly indicate thathydrogen bonds and van der Waals forces play a major role in the binding process between albumin and betamethasone, flunisolide and prednisolone, while hydrophobic forces may play a major role in stabilizing albumin-triamcinolone complexes.
基金This study was supported by National Clinical Key Specialty Project Foundation,2015 National Health and Family Planning Commission Special Fund(201502025)Natural Science Foundation of Guangdong(2014A030313146,2016A030313302,2016A030311046 and 2017A030313537)+2 种基金Guangzhou Science and Technology Plan(201709010030)the Scientific Research Project of Guangzhou Municipal Universities(1201630019)National Natural Science Foundation of China(31600710 and 81700645).
文摘Background:Inhaled corticosteroids (ICSs) for treating asthma are controversial because of their negative effects on the growth of asthmatic children and without clearly defined withdrawal strategy.A 2-year ICS step-down and withdrawal strategy has been developed for asthmatic children receiving 3-year subcutaneous immunotherapy (SCIT).Methods:Eleven children were included into the SCIT group and 13 children into the ICS group.ICSs were discontinued when children met the following criteria:requiring only 1 puff per day,with good control,for at least 6 months;having a forced expiratory volume in 1 second (FEV1)/forced vital capacity ≥80%;and SCIT discontinued for ≥24 months.The main endpoints were the results of both the childhood asthma control test (C-CAT) and the methacholine bronchial provocation test.Results:In the SCIT group,all the 11 children had ICS discontinued,with one child developed asthma attack after pneumonia and received ICS again after completion of SCIT.In the ICS group,five children discontinued ICS and developed asthma attacks later and received ICS again;the other eight children developed severe symptoms during ICS step-down.Thus,the discontinuation of ICS was only achieved in the SCIT group.The dose of methacholine that caused a decrease of 20% in FEV1 continued to improve after discontinuation of ICS for the SCIT group and presented better results than the ICS group (P=-0.050).After completion of SCIT,the C-CAT had improved significantly after 30 months of treatment compared with the ICS group (P<0.05).Conclusion:In the present study,we developed a 2-year step-down and withdrawal strategy from ICSs strategy for allergic asthma children receiving SCIT;the strategy was efficacious and safe.
