Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell-derived cytokine implicated in the pathogenesis of asthma. It was approved by the United States Federal Drug Administration (US FDA) as an add-on maintenance treatment for patients with severe uncontrolled asthma in December 2021. We conducted a systematic review and meta-analysis to investigate the safety and efficacy of tezepelumab on forced expiratory volume (FEV 1 ) (L), the rate of asthma exacerbations, health-related quality of life, fractional exhaled nitric oxide (FeNO) (ppb), and blood eosinophil count (cells/mL) in patients with severe, uncontrolled asthma. Mean changes for efficacy and proportions (safety) with their corresponding 95% confidence intervals (CIs) were used to provide pooled estimates. A total of six randomized controlled trials comprising 2667 patients were included, of whom 1610 were treated with tezepelumab and 1057 received placebo. The pooled analysis showed that tezepelumab treatment resulted in an improvement in FEV 1 of 0.15 L (95% CI: 0.12 to 0.17), a reduction in the asthma exacerbation rate per year of 0.60 (95% CI: 0.51 to 0.70), and a reduction in FeNO of −12.41 ppb (95% CI: −14.28 to −10.53) when compared to placebo. Improvements in FEV 1 and FeNO levels were maintained at 24 and 52 weeks. As for safety, patients did not experience a higher incidence of adverse drug reactions with tezepelumab (0.79 (95% CI: 0.55 to 1.12)) as compared to placebo. As for quality of life, different doses of the tezepelumab intervention group depicted non-significant improvement in the QoL, from 0.15 (95% CI: −0.09 to 0.38) for 70 mg, 0.18 (95% CI: −0.10 to 0.46) for 210 mg, 0.08 (95% CI: −0.16 to 0.32) for 280 mg as compared to the placebo. Tezepelumab significantly reduced exacerbation rates and improved FEV 1 with an acceptable safety profile.
Poster sessionsThorax 2012;67(Suppl 2):A1-A204 A81Results Of 243 CPET tests performed during this period, 68 (28%) were done to evaluate UB&EI. 38 patients(56%) were obese. Overall, obesity was the sole cause of UB&EI in 22 patients (32%) and was a contributory factor in a further 15 patients (22%). In the obese subgroup, it was the sole cause in 21 patients (55%) and contributory in a further 16 patients (43%). Being overweight (BMI 29) was the sole cause of unexplained breathlessness in 1 non-obese patient. Obesity appeared to be the major contributing factor for UB&EI even when present with other factors. In 23 patients (34%) more than one contributory factor was present (Cardiovascular/ Respiratory/VQ mismatch/physical de-conditioning/functional). Physical de-conditioning was the sole cause in 5 patients (7%) and Hyperventilation in 2 patients (3%). Conclusion While the causes of UB&EI are multi factorial, in our study obesity was a contributory and often key factor in over half the patients. In the obese subgroup, being overweight was the sole factor in over half and played a contributory role in almost all patients. CPET is a useful test to determine specific causes of UB&EI when resting cardio-respiratory tests are non-contributory and can help with reassurance, dietary advice and exercise prescription.
SummaryA 69-year-old man presented to the emergency department after being found unconscious by his son. He had experienced headache the previous day but had been otherwise well. Investigations revealed a severe metabolic acidosis, raised lactate and acute kidney injury. The calculated anion and osmolar gap were both elevated at 37.7 and 39.3, respectively. Due to his reduced Glasgow coma score (GCS) he was intubated and a CT scan performed: only a small, mature pontine infarct was found of uncertain significance. Further questioning of the family revealed accidental ingestion of 150 ml of a 'blue liquid' 24 h earlier (later identified as car screenwash). With ethylene glycol (EG) poisoning suspected, he was given intravenous ethanol, fomepizole (a competitive inhibitor of alcohol dehydrogenase) and haemofiltration. Despite the delayed presentation, prompt recognition and treatment of EG poisoning led to a successful discharge in this case. BACKGROUND
course and history of long term survivors and we describe characteristics and outcomes of all lung transplant recipients who have survived greater than 20 years at our centre. Results Twenty-one (16.2%) out of a possible total of 121 transplant patients survived at least 20 years with an overall median survival of 21.3 (range 20.1-24.9) years. The mean age at transplantation was 31.8 ± 9.9 years and 13 (61.9%) were male. The most common indication for transplantation in the group was Cystic Fibrosis (33.3%); heart-lung and bilateral lung transplant operations were equally the most commonly performed.The median six-minute walk distance (6MWD) was 600m (range 419-785m). The median time to the development of BOS was 9.7 years. At time of evaluation, 2 (10%) patients had BOS score 0, 3 (14%) BOS 1, 6 (29%) BOS 2 and 10 (48%) BOS 3.The total number of rejections requiring augmentation with corticosteroids was 30 episodes in 21 patients with an average of 1.4 (range 0-3) episodes per patient. Eighteen patients had at least one episode of rejection needing corticosteroids.No patient developed symptomatic ischaemic heart disease; systemic hypertension was found in 19 (90.5%) patients. Two (9.5%) patients developed post-transplant lymphoproliferative disease. Four patients developed other malignancies, 3 of which were skin cancers and 1 renal cancer.All 4 cases of diabetes post transplantation occurred in patients with Cystic Fibrosis. Eight patients required renal replacement therapy as a result of ciclosporin toxicity and four underwent renal transplantation. Conclusion Twenty-one (16.2%) patients in our cohort survived 20 years. Although nearly all patients developed an element of CLAD, exercise tolerance was preserved as judged by 6MWD. Hypertension was common and renal failure remained the most problematic complication of immunosuppression. Rationale Lung transplantation has become an accepted treatment option in a select group of patients with end-stage lung disease. The current International Society for Heart and Lung Transplantation (ISHLT) guidelines suggest age above 65 is a relative contraindication. However, increasingly patients with COPD and IPF are being referred for consideration after this age. The outcomes in this group (above 65) are not well described. We have studied the characteristics and outcomes of patients aged 65 and over, offered lung transplantation in our institution. Method Retrospective review from the transplant database and patient records. We examined the Age, Sex, Indication for transplant and cause of death in all transplant recipients aged 65 and over from 1991 to July 2013. As a control group we compared them with 50 single lung transplant recipients front the same era and institution who were under 65. We used SPSS to generate the survival curves. Results In total we had 19 lung transplant recipients aged 65 and over who all had a single lung transplant, with a mean survival of 1600 days post-transplant. 13/19 were male recipients.The indication for transplantation was COPD and IPF...
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