BACKGROUND:Traditionally, forced expiratory volume in one second (FEV1) was used to evaluate exercise response of patients with asthma; however, patients obviously had panting after exercise, so FEV1 was affected commonly. Impulse oscillometry (IOS) is a new technique for measuring respiratory impedance that do not require maximal inspiration and forced expiration.OBJECTIVE: To study airway resistance with IOS before and after exercise in healthy and asthmatic patients and investigate the significance of exercise excitation and IOS assessment.DESIGN: Synchronically non-randomized case contrast study.SETTING: Department of Respiratory Medicine, East Hospital Affiliated to Tongji University.PARTICIPANTS: A total of 14 male patients with bronchial asthma who were regarded as the asthmatic group were selected from Department of Respiratory Medicine of Shanghai East Hospital from January to October 2006. They were in a clinical stationary phase. Another 14 male healthy subjects were selected as the control group and ages of all subjects ranged from 29 to 50 years. All subjects provided the confirmed consent.METHODS: IOS was used to measure basic value of respiratory resistance, and then subjects underwent exercise challenge. Nose of subjects was clipped breathing through mouth. Within 3-4 minutes, heart rate was increased to 90% and maintained for 6 minutes during challenge. Respiratory resistance was repeatedly measured at 1, 5, 10, 15 and 20 minutes after exercise, including airway hyperresponse (AHR), total respiratory resistance, central resistance, peripheral resistance and resonance frequency at 5, 20 and 35 Hz of pulse frequency, elasrtic resistance and inertia resistance (X5 and X35) at 5 and 10 Hz of pulse frequency. In addition, difference of AHR at 5 and 35 Hz was calculated, and change ratios of both Rcentral and Rperipheral were calculated as (highest value after exercise-baseline value)/baseline value × 100%.MAIN OUTCOME MEASURES: Basic value of respiratory resistance by using IOS and exercise challenge test.RESULTS: All 14 patients with bronchial asthma and 14 healthy subjects were involved in the final analysis. Peripheral resistance (Rperiphera) was significantly higher than central resistance (Rcentral) in asthmatic patients (P ＜ 0.01). The maximal increase of respiratory impedance occurred from 5 minutes to 10 minutes after exercise in asthmatics. Resonance frequency (Fres) of asthmatics before and after exercise was significantly increased than that of controls (P ＜ 0.01).Change ratios of Fres from asthmatics were higher than that from control group (P ＜ 0.01). After challenge, R5, R5-R20,Zrespir and X5 from asthmatics changed significantly than that from controls (P ＜ 0.01). The increment change value of After exercise Zrespir increased significantly, because obstruction of small bronchi during expiration and impedance increased abruptly. Air trapping was expressed in VT-Zrespir graph in 57.1% patients. There was no difference in the VT-Zrespir graph of controls before and after exercise.CONCLUSION: The main site of airflow obstruction was in small airways in asthmatics after exercise challenge. The general acceptance of IOS method was good among the asthmatic patients. The airway response of exercise challenge may be assessed more accurately with IOS that do not require a maximal inspiration and forced expiration.

Objective : To investigate the effect and mechanism of all-trans retinoic acid (ATRA) on lipopolysaccharide (LPS) -induced acute myocardial injury in C57BL/6 mice． Methods : Male mice of C57BL/6 strain were randomly divided into normal group，model group，ATRA group，and ferrostatin-1 group．Mice in the ATRA group were injected intraperitoneally with ATRA 15mg / (kg · d) ，ferrostatin-1 group received ferrostatin-1 2 mg / ( kg · d) ，the normal group and the model group were given solvent．After one week of continuous administration，the model group，ATRA group ，and ferrostatin-1 group were intraperitoneally injected with LPS 6 mg / kg． All mice were sacrificed after 6 hours．The contents of malondialdehyde ( MDA) and glutathione ( GSH) in serum of mice were detected． qPCR was used to detect mRNA levels of interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha (TNF-α) in heart tissue．Hematoxylin-eosin ( HE) staining was used to observe the changes of heart tissue in mice．Transmission electron microscopy (TEM) was used to observe the structure of mouse myocardial mitochondria．Western blot was used to detect the expression of ferroptosis markers glutathione peroxidase 4 ( GPX4) ，ferritin heavy chain 1 ( FTH1 ) ，Solute carrier family 7 member 11 ( SLC7A11 ) ，acyl-CoA synthetase long-chain family member 4 (ACSL4) and related regulatory proteins，Nuclear factor erythroid 2-related factor 2 ( NRF2 ) ，kelchlike ECH-associated protein 1 (KEAP1) . Results: Compared with the normal group，the MDA content in the serum of the model group increased and the GSH content decreased，the above changes were reversed in the ATRA group as well as in the ferrostatin-1 group．Compared with normal group，the mRNA levels of IL-6 and TNF-α in the heart tissue of model group increased steeply，the above changes were relieved in the ATRA group and the ferrostatin-1 group．There was no significant difference in HE staining of myocardial tissue among the groups of mice. Compared with the normal group，myocardial mitochondria in the model group showed the phenomenon of cristaereduction or disappearance under TEM，while myocardial mitochondrial injury was alleviated in the ATRA group and the ferrostatin-1 group．Western blot showed that GPX4，FTH1，SLC7A11，and NRF2 expression were reduced in the myocardial tissue of mice in the model group compared with the normal group，ACSL4 and KEAP1 expression increased．The above changes were reversed in the ATRA group as well as in the ferrostatin-1 group． Conclusion ATRA alleviates lipopolysaccharide-induced acute myocardial injury in mice by inhibiting ferroptosis.