Patients with severe uncontrolled asthma still experience acute asthma symptoms and exacerbations, particularly those with non-eosinophilic inflammation who take the maximum amount of standard drug therapy. Tezepelumab, a human monoclonal antibody, can improve lung function and enhance control of asthma symptoms in those patients, regardless of the disease’s baseline characteristics. This study aims to investigate the safety and efficacy of using tezepelumab in controlling severe symptoms of uncontrolled asthma. We performed a comprehensive literature search in several databases, including PubMed, Scopus, Web of Science, Cochrane Library, and clinicaltrial.gov, using a well-established search strategy to include all relevant publications. According to our inclusion criteria, we searched for randomized controlled trials comparing tezepelumab versus placebo in patients with severe, uncontrolled asthma. We analyzed the data using The Revman 5.4 program software. The search identified 589 potential articles. After excluding studies inconsistent with selection criteria, four studies were included and analyzed qualitatively and quantitatively. The pooled effect demonstrated the better performance of tezepelumab over the placebo regarding the decrease in annualized asthma exacerbation rate (MD = − 0.74, (95% CI [− 1.04, − 0.44], p < 0.00001)), asthma control questionnaire-6 (ACQ-6) Score MD = − 0.32, (95% CI [− 0.43, − 0.21], p < 0.00001)), blood eosinophil count (MD = − 139.38 cells/mcL, (95% CI [− 150.37, − 128.39], p < 0.00001)), feNO (MD = − 10 ppb, (95% CI [− 15.81, − 4.18], p = 0.0008)) and serum total IgE (MD = − 123.51 UI/ml, (95% CI [− 206.52, − 40.50], p = 0.004)). All tezepelumab groups had higher pre-bronchodilator forced expiratory volume in 1 s than the placebo group (MD = 0.16, (95% CI [0.10, 0.21], p < 0.00001)). Higher efficacy and safety profile was detected for tezepelumab to control the exacerbations of severe uncontrolled adult asthmatics.

Background Sildenafil was first prescribed for angina pectoris and then for erectile dysfunction from its effects on vascular smooth muscle relaxation and vasodilatation. Recently, sildenafil has been proposed for congenital heart diseases induced pulmonary hypertension, which constitutes a huge burden on children's health and can attribute to fatal complications due to presence of unoxygenated blood in the systemic circulation. Therefore, our meta-analysis aims to further investigate the safety and efficacy of sildenafil on children population. Methods We searched the following electronic databases: PubMed, Cochrane CENTRAL, WOS, Embase, and Scopus from inception to April 20th, 2022. Randomized controlled trials that assess the efficacy of using sildenafil in comparison to a placebo or any other vasodilator drug were eligible for inclusion. The inverse variance method was used to pool study effect estimates using the random effect model. Effect sizes are provided in the form of mean difference (MD) with 95% confidence intervals (CI). Results Our study included 14 studies with (n = 849 children) with a mean age of 7.9 months old. Sildenafil showed a statistically significant decrease over placebo in mean and systolic pulmonary artery pressure (PAP) with MD -7.42 (95%CI [-13.13, -1.71], P = 0.01) and -8.02 (95%CI [-11.16, -4.88], P < 0.0001), respectively. Sildenafil revealed a decrease in mean aortic pressure and pulmonary artery/aortic pressure ratio over placebo with MD -0.34 (95%CI [-2.42, 1.73], P = 0.75) and MD -0.10 (95%CI [-0.11, -0.09], P < 0.00001), respectively. Regarding post corrective operations parameters, sildenafil had a statistically significant lower mechanical ventilation time, intensive care unit stay, and hospital stay over placebo with MD -19.43 (95%CI [-31.04, -7.81], s = 0.001), MD -34.85 (95%CI [-50.84, -18.87], P < 0.00001), and MD -41.87 (95%CI [-79.41, -4.33], P = 0.03), respectively. Nevertheless, no difference in mortality rates between sildenafil and placebo with OR 0.25 (95%CI 0.05, 1.30], P = 0.10) or tadalafil with OR 1 (95%CI 0.06, 17.12], P = 1). Conclusion Sildenafil is a well-tolerated treatment in congenital heart diseases induced pulmonary hypertension, as it has proven its efficacy not only in lowering both PAP mean and systolic but also in reducing the ventilation time, intensive care unit and hospital stay with no difference observed regarding mortality rates.

Background: PDE5 inhibitors (PDE5-Is) manifest its effects by inhibiting the PDE5 dependent cGMP hydrolysis, thus increasing cGMP intracellularly which results in vascular smooth muscles relaxation and vasodilatation. PDE 5 inhibitors, such as sildenafil, were first prescribed for angina pectoris then for erectile dysfunction (ED). Recently, sildenafil has been proposed in congenital heart diseases (CHD) induced PAH, which constitute a huge burden on children health and can attribute to fatal complications due to the un-oxygenated blood presents in the systemic circulation. Therefore, our meta-analysis aims to further investigate the safety and efficacy of sildenafil in CHD induced PH. Methods: We searched the following electronic databases: PubMed, Cochrane CENTRAL, WOS, Embase, and Scopus from inception to April 20th, 2022. Randomized controlled trials that assess the efficacy of using sildenafil in comparison to placebo or any other vasodilator drug were eligible for inclusion. The inverse variance method was used to pool study effect estimates using random effect model. Effect sizes are provided in the form of mean difference (MD) with 95% confidence intervals (CI). Results: Our study included 14 studies with (n = 849 children) with a mean age of 7.9 months old. Sildenafil showed statistically significant decrease over placebo in mPAP and sPAP with MD -7.42 (95%CI [-13.13, -1.71], P = 0.01) and − 8.02 (95%CI [-11.16, -4.88], P < 0.0001), respectively. Sildenafil revealed a decrease in mAOP and PA/OA ratio over placebo with MD -0.34 (95%CI [-2.42, 1.73], P = 0.75) and MD -0.10 (95%CI [-0.11, -0.09], P < 0.00001), respectively. Regarding post-operative parameters, sildenafil had a statistically significant lower mechanical ventilation time, ICU stay, and hospital stay over placebo with MD -19.43 (95%CI [-31.04, -7.81], P = 0.001), MD -34.85 (95%CI [-50.84, -18.87], P < 0.00001), and MD -41.87 (95%CI [-79.41, -4.33], P = 0.03), respectively. Nevertheless, no difference in mortality rates between sildenafil and placebo with OR 0.25 (95%CI 0.05, 1.30], P = 0.10) or tadalafil with OR 1 (95%CI 0.06, 17.12], P = 1). Conclusion: Sildenafil is a well-tolerated treatment in congenital heart diseases induced pulmonary hypertension, as it has proven its efficacy not only in lowering the mPAP and sPAP, but also in reducing the ventilation time, ICU and hospital stay with no difference observed regarding mortality rates.

Background: Patients with severe uncontrolled asthma still experience acute asthma symptoms and exacerbations, particularly those with non-eosinophilic inflammation who take the maximum amount of standard drug therapy. Tezepelumab, a human monoclonal antibody, can improve lung function and enhance control of asthma symptoms in those patients, regardless of the disease's baseline characteristics. This study explores the safety and efficacy of using tezepelumab in controlling severe symptoms of uncontrolled asthma.Methods and procedures: We performed a comprehensive literature search in several databases, including PubMed, Scopus, Web of Science, Cochrane Library, and clinicaltrial.gov, using a well-established search strategy to include all relevant publications. As our inclusion criteria, we looked for randomized controlled trials comparing tezepelumab versus placebo in patients with severe, uncontrolled asthma. We analysed the data using The Revman 5.4 programme software.Outcome and Results: The search identified 589 potential articles. After excluding studies inconsistent with selection criteria, four studies were included and analysed qualitatively and quantitatively. The pooled effect demonstrated the better performance of tezepelumab over the placebo regarding the decrease in Annualized asthma exacerbation rate (MD =-0.74, p<0.00001)), Asthma Control Questionnaire-6 (ACQ-6) Score MD = -0.32, p<0.00001), Blood eosinophil count (MD = -139.38, p<0.00001), feNO (MD = -10, p=0.0008) and Serum IgE (MD = -123.51, p=0.004). All tezepelumab groups had higher pre-bronchodilator forced expiratory volume in 1 second than the placebo group (MD=0.16, p0.00001).Conclusion: tezepelumab is effective and safe in lowering asthma exacerbations in individuals with severe uncontrolled asthma.