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1.
Eur J Pediatr ; 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34091748

RESUMO

Persistent pulmonary hypertension of the neonate (PPHN) refractory to inhaled nitric oxide still represents a frequent clinical challenge with negative outcomes in neonatal critical care. Several pulmonary vasodilators have become available thanks to improved understanding of pulmonary hypertension pathobiology. These drugs are commonly used in adults and there are numerous case series and small studies describing their potential usefulness in neonates, as well. New vasodilators act on different pathways, some of them can have additive effects and all have different pharmacology features. This information has never been summarized so far and no comprehensive pathobiology-driven algorithm is available to guide the treatment of refractory PPHN.Conclusion: We offer a rational clinical algorithm to guide the treatment of refractory PPHN based on expert advice and the more recent pathobiology and pharmacology knowledge. What is Known: • Refractory PPHN occurs in 30-40% of iNO-treated neonates and represents a significant clinical problem. Several pulmonary vasodilators have become available thanks to a better understanding of pulmonary hypertension pathobiology. What is New: • Available vasodilators have different pharmacology, mechanisms of action and may provide additive effect. We provide a rational clinical algorithm to guide the treatment of refractory PPHN based on expert advice and the more recent pathobiology and pharmacology knowledge.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34144110

RESUMO

BACKGROUND: Managing severe asthma during the SARS-CoV-2 pandemic is challenging, particularly due to safety concerns regarding the use of systemic corticosteroids and biologics. OBJECTIVES: To determine the association between biologics or systemic corticosteroids use with PCR positivity for SARS-CoV-2 and COVID-19 outcomes among asthmatic patients METHODS: We used the computerized database of Clalit Health Services, the largest healthcare provider in Israel, to identify all asthmatic adult patients who underwent PCR testing for SARS-CoV-2, between 1st of March 2020 and 7th December 2020. A cohort approach was used to assess the association between biologics use and steroids treatment and COVID-19 severity and 90-day mortality. RESULTS: Overall, 8,242 out of 80,602 tested asthmatics had positive PCR testing for SARS-CoV-2. Both biologics and systemic corticosteroids were not associated with increased risk of SARS-CoV-2 infection. Multivariate analyses revealed that biologics were not associated with a significant increased risk of moderate-severe COVID-19, nor with the composite endpoint of moderate-severe COVID-19 or all-cause mortality within 90 days. Chronic systemic corticosteroids use was associated with significant increased risk of all tested outcome. Recent (within the prior 120 days) systemic corticosteroids use, but not former use, was significantly associated with increased risk of both moderate-severe COVID-19 and the composite of moderate-severe COVID-19 or all-cause mortality. CONCLUSION: Biologics approved for asthma and systemic corticosteroids are not associated with increased risk of SARS-CoV-2 infection. By contrast, systemic corticosteroids are independent risk factor for worst COVID-19 severity and all-cause mortality. Our findings underscore the risk of recent or current exposure to systemic corticosteroids in asthmatics infected with SARS-CoV-2.

3.
J Clin Immunol ; 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34110542

RESUMO

PURPOSE: Common variable immunodeficiency (CVID) is known to cause infectious, inflammatory, and autoimmune manifestations. Pulmonary hypertension (PH) is an unusual complication of CVID with largely unknown characteristics and mechanisms. METHODS: We report the clinical, functional, hemodynamics, radiologic and histologic characteristics, and outcomes of CVID-associated PH patients from the French PH Network. RESULTS: Ten patients were identified. The median (range) age at CVID diagnosis was 36.5 (4-49) years and the median delay between CVID and PH diagnosis was 12 (0-30) years. CVID-associated PH affected predominantly women (female-to-male ratio 9:1). Most patients were New York Heart Association functional class III with a severe hemodynamic profile and frequent portal hypertension (n = 6). Pulmonary function tests were almost normal in 70% of patients and showed a mild restrictive syndrome in 30% of patients while the diffusing capacity for carbon monoxide was decreased in all but one patient. High-resolution computed tomography found enlarged mediastinal nodes, mild interstitial infiltration with reticulations and nodules. Two patients had a CIVD-interstitial lung disease, and one presented with bronchiectasis. Pathologic assessment of lymph nodes performed in 5 patients revealed the presence of granulomas (n = 5) and follicular lymphoid hyperplasia (n = 3). At last follow-up (median 24.5 months), 9 patients were alive, and one patient died of Hodgkin disease. CONCLUSION: PH is a possible complication of CVID whose pathophysiological mechanisms, while still unclear, would be due to the inflammatory nature of CVID. CVID-associated PH presents as precapillary PH with multiple possible causes, acting in concert in some patients: a portal hypertension, a pulmonary vascular remodeling, sometimes a pulmonary parenchymal involvement and occasionally an extrinsic compression by mediastinal lymphadenopathies, which would be consistent with its classification in group 5 of the current PH classification.

4.
Cardiovasc Res ; 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34086873

RESUMO

AIMS: BMP9 and BMP10 mutations were recently identified in patients with pulmonary arterial hypertension (PAH), but their specific roles in the pathogenesis of the disease are still unclear. We aimed to study the roles of BMP9 and BMP10 in cardiovascular homeostasis and pulmonary hypertension using transgenic mouse models deficient in Bmp9 and/or Bmp10. METHODS AND RESULTS: Single- and double-knockout mice for Bmp9 (constitutive) and/or Bmp10 (tamoxifen inducible) were generated. Single-KO mice developed no obvious age-dependent phenotype when compared with their wild-type littermates. However, combined deficiency in Bmp9 and Bmp10 led to vascular defects resulting in a decrease in peripheral vascular resistance and blood pressure and the progressive development of high-output heart failure (HOHF) and pulmonary hemosiderosis. RNAseq analysis of the lungs of the double-KO mice revealed differential expression of genes involved in inflammation and vascular homeostasis. We next challenged these mice to chronic hypoxia. After three weeks of hypoxic exposure, Bmp10-cKO mice showed an enlarged heart. However, although genetic deletion of Bmp9 in the single and double-KO mice attenuated the muscularization of pulmonary arterioles induced by chronic hypoxia, we observed no differences in Bmp10-cKO mice. Consistent with these results, endothelin-1 levels were significantly reduced in Bmp9 deficient mice but not Bmp10-cKO mice. Furthermore, the effects of BMP9 on vasoconstriction were inhibited by bosentan, an endothelin receptor antagonist, in a chick chorioallantoic membrane assay. CONCLUSIONS: Our data show redundant roles for BMP9 and BMP10 in cardiovascular homeostasis under normoxic conditions (only combined deletion of both Bmp9 and Bmp10 was associated with severe defects) but highlight specific roles under chronic hypoxic conditions. We obtained evidence that BMP9 contributes to chronic hypoxia-induced pulmonary vascular remodeling, whereas BMP10 plays a role in hypoxia-induced cardiac remodeling in mice.

6.
Circulation ; 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34078089

RESUMO

Background: Epigenetic mechanisms are critical in the pathogenesis of pulmonary arterial hypertension (PAH). Previous studies have suggested that hypermethylation of the Bone Morphogenetic Protein Receptor Type 2 (BMPR2) promoter is associated with BMPR2 downregulation and progression of PAH. Here, we investigated for the first time the role of Switch-Independent 3a (SIN3a), a transcriptional regulator, in the epigenetic mechanisms underlying hypermethylation of BMPR2 in the pathogenesis of PAH. Methods: We used lung samples from PAH patients and non-PAH controls, preclinical mouse and rat PAH models, and human pulmonary arterial smooth muscle cells (hPASMC). Expression of SIN3a was modulated using a lentiviral vector or a siRNA in vitro and a specific Adeno-Associated Virus serotype 1 (AAV1) or a lentivirus encoding for human SIN3a in vivo. Results: SIN3a is a known transcriptional regulator; however, its role in cardiovascular diseases, especially PAH, is unknown. Interestingly, we detected a dysregulation of SIN3 expression in patients and in rodent models, which is strongly associated with decreased BMPR2 expression. SIN3a is known to regulate epigenetic changes. Therefore, we tested its role in the regulation of BMPR2 and found that BMPR2 is regulated by SIN3a. Interestingly, SIN3a overexpression inhibited hPASMC proliferation and upregulated BMPR2 expression by preventing the methylation of the BMPR2 promoter region. RNA sequencing analysis suggested that SIN3a downregulated the expression of DNA and histone methyltransferases such as DNMT1 and EZH2 while promoting the expression of the DNA demethylase TET1. Mechanistically, SIN3a promoted BMPR2 expression by decreasing CTCF binding to the BMPR2 promoter. Finally, we identified intratracheal delivery of AAV1.hSIN3a to be a beneficial therapeutic approach in PAH- by attenuating pulmonary vascular and RV remodeling, decreasing RVSP and mPAP pressure, and restoring BMPR2 expression in rodent models of PAH. Conclusions: Altogether, our study unveiled the protective/beneficial role of SIN3a in pulmonary hypertension. We also identified a novel and distinct molecular mechanism by which SIN3a regulates BMPR2 in hPASMC. Our study also identified lung-targeted SIN3a gene therapy using AAV1 as a new promising therapeutic strategy for treating patients with PAH.

8.
Orphanet J Rare Dis ; 16(1): 196, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933110

RESUMO

BACKGROUND: During the COVID-19 pandemic, most of the health care systems suspended their non-urgent activities. This included the cancellation of consultations for patients with rare diseases, such as severe pulmonary hypertension (PH), resulting in potential medication shortage and loss of follow-up. Thus, the aim of the study was to evaluate PH patient health status evolution, access to health care and mental health experience during the early phase of the pandemic. METHODS: We conducted an online patient survey, available in 16 languages, between 22/05/2020 and 28/06/2020. The survey included questions corresponding to demographic, COVID-19 and PH related information. RESULTS: 1073 patients (or relatives, 27%) from 52 countries all over the world participated in the survey. Seventy-seven percent (77%) of responders reported a diagnosis of pulmonary arterial hypertension and 15% of chronic thromboembolic PH. The COVID-19 related events were few: only 1% of all responders reported a diagnosis of COVID-19. However, 8% of patients reported health deterioration possibly related to PH, and 4% hospitalization for PH. Besides, 11% of the patients reported difficulties to access their PH expert centre, and 3% interruption of treatment due to shortage of medication. Anxiety or depression was reported by 67% of the participants. CONCLUSION: Although COVID-19 incidence in PH patients was low, PH related problems occurred frequently as the pandemic progressed, including difficulties to have access to specialized care. The importance of primary health care was emphasized. Further studies are needed to evaluate the long-term consequences of COVID-related PH care disruption.


Assuntos
COVID-19 , Hipertensão Pulmonar , Ansiedade , Humanos , Hipertensão Pulmonar/epidemiologia , Pandemias , SARS-CoV-2
11.
Am J Transplant ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33844424

RESUMO

Patients with end-stage pulmonary arterial hypertension due to congenital heart disease have limited access to heart-lung transplantation or double-lung transplantation. We aimed to assess the effects of a high-priority allocation program established in France in 2007. We conducted a retrospective study to compare waitlist and post-transplantation outcomes before versus after implementation of the high-priority allocation program. We included 67 consecutive patients (mean age at listing, 33.2±10.5 years) with pulmonary arterial hypertension due to congenital heart disease listed for heart-lung transplantation or double-lung transplantation from 1997 to 2016. At one month, the incidences of transplantation and death before transplantation were 3.5% and 24.6% in 1997-2006, 4.8% and 4.9% for patients on the regular list in 2007-2016, and 41.2% and 7.4% for patients listed under the high-priority allocation program (P<0.001 and P=0.0001 respectively). Overall survival was higher in patients listed in 2007-2016 (84.2% and 61.2% at 1 and 10 years versus 36.8% and 22.1%, P=0.0001). Increased incidence of transplantation, decreased waiting list mortality, and improved early and long-term outcomes were observed in patients with pulmonary arterial hypertension due to congenital heart disease listed for transplantation in the recent era, characterized by implementation of a high-priority allocation program.

12.
Eur Respir J ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33875491

RESUMO

RATIONALE: Drugs approved for the treatment of pulmonary arterial hypertension (PAH) improve long-term outcomes. These drugs have pulmonary vasodilator properties which may potentially cause a decrease in arterial oxyhaemoglobin saturation (SaO2) in some patients. OBJECTIVES: The present retrospective study of the French PAH Registry aimed to describe clinical characteristics and outcomes of patients showing a ≥3% decrease in SaO2 while treated with PAH drugs. METHODS: We reviewed 719 PAH patients. The exclusion criteria were PAH associated with congenital heart disease and PAH with overt features of venous/capillaries involvement. MAIN RESULTS: One hundred and seventy-three (24%) patients had a ≥3% decrease in SaO2. At diagnosis, they were older, with a lower diffusion capacity for carbon monoxide and a shorter 6-minute walk distance, when compared to those who did not display a ≥3% decrease in SaO2. The percentage of patients meeting the ESC/ERS low risk criteria at re-evaluation was significantly lower in those with a ≥3% decrease in SaO2 and more patients started long-term oxygen therapy in this group (16% versus 5%, p<0.001). A≥3% decrease in SaO2 was associated with a poorer survival (Hazard Ratio 1.81:95% confidence interval 1.43-2.34; p<0.0001). In a multivariate Cox analysis, a ≥3% decrease in SaO2 was a prognostic factor independent of age at diagnosis and ESC/ERS risk stratification at follow-up. CONCLUSIONS: When treated with PAH drugs, a large subset of patients experience a≥3% decrease in SaO2, which is associated with worst long-term outcomes and reduced survival.

13.
Eur Respir J ; 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-33926975

RESUMO

INTRODUCTION: A reduction in pulmonary artery (PA) relaxation is a key event in pulmonary arterial hypertension (PAH) pathogenesis. CFTR dysfunction in airway epithelial cells plays a central role in cystic fibrosis (CF); CFTR is also expressed in PAs and has been shown to control endothelium-independent relaxation. AIM AND OBJECTIVES: We aimed to delineate the role of CFTR in PAH pathogenesis through observational and interventional experiments in human tissues and animal models. METHODS AND RESULTS: RT-Q-PCR, confocal imaging and electron microscopy showed that CFTR expression was reduced in PAs from patients with idiopathic PAH (iPAH) and in rats with monocrotaline-induced pulmonary hypertension (PH). Moreover, using myograph on human, pig and rat PAs, we demonstrated that CFTR activation induces PAs relaxation. CFTR-mediated PA relaxation was reduced in PAs from iPAH patients and rats with monocrotaline- or chronic hypoxia-induced PH. Long-term in vivo CFTR inhibition in rats significantly increased right ventricular systolic pressure, which was related to exaggerated pulmonary vascular cell proliferation in situ and vessel neomuscularization. Pathologic assessment of lungs from patients with severe CF (F508del-CFTR) revealed severe PA remodeling with intimal fibrosis and medial hypertrophy. Lungs from homozygous F508delCftr rats exhibited pulmonary vessel neomuscularization. The elevations in right ventricular systolic pressure and end diastolic pressure in monocrotaline-exposed rats with chronic CFTR inhibition were more prominent than those in vehicle-exposed rats. CONCLUSIONS: CFTR expression is strongly decreased in PA smooth muscle and endothelial cells in human and animal models of PH. CFTR inhibition increases vascular cell proliferation and strongly reduces PA relaxation.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33849770

RESUMO

PURPOSE: Pulmonary arterial hypertension (PAH) is rare but remains fatal in infants and children despite the advance of targeted therapies. Lung transplantation (LTx), first performed in pediatric patients in the 1980s, is, with the Potts shunt, the only potentially life-extending option in patients with end-stage PAH but is possible only in tightly selected patients. Size-matching challenges severely restrict the donor organ pool, resulting-together with peculiarities of PAH in infants-in high waitlist mortality. We aimed to investigate survival when using a high-priority allocation program (HPAP) in children with PAH listed for double-LTx or heart-LTx. METHODS: We conducted a single-center, retrospective, before-after study of consecutive children with severe Group 1 PAH listed for double-LTx or heart-LTx between 1988 and 2019. The HPAP was implemented in France in 2006 and 2007 for heart-LTx and double-LTx, respectively. RESULTS: Fifty-five children with PAH were listed for transplantation. Mean age at transplantation was 15.8±2.8 years and 72% had heart-lung transplantation. PAH was usually idiopathic (65%) or due to congenital heart disease (25%). HPAP implementation resulted in the following significant benefits: Decreased cumulative incidence of waitlist death within 1 and 2 years (p < 0.0001); increased cumulative incidence of transplantation within 6 months, from 44% to 67% (p < 0.01); and improved survival after listing (at 1, 3, and 5 years: 61%, 50%, and 44% vs. 92%, 84%, and 72% before and after HPAP implementation, respectively; p = 0.02). CONCLUSION: HPAP implementation was associated with significant improvements in access to transplantation and in survival after listing in children with end-stage PAH.

17.
BMC Geriatr ; 21(1): 153, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653285

RESUMO

BACKGROUND: Transcatheter aortic valve replacement is increasingly performed in frail older patients who were previously ineligible for a standard surgical procedure. The objectives of this study are to determine delirium incidence, predictors, and relationship with cognitive performance at 3-month follow-up in older patients undergoing aortic valve replacement (AVR). METHODS: Patients (N = 93) aged 70 years and older, undergoing transcatheter (TAVR, N = 66) or surgical (SAVR, N = 27) aortic valve replacement in an academic medical center were enrolled in this prospective cohort study. Delirium was assessed using the Confusion Assessment Method (CAM) on postoperative days 1, 2, 3, and 7. Data on patients' socio-demographics, functional status (including instrumental activities of daily living (IADL), and surgical risk scores (including Society of Thoracic Surgeons (STS) risk score), were collected at baseline. Cognitive status was assessed with the Mini-Mental Status Exam (MMSE) and the Clock Drawing Test (CDT) at baseline and 3 months after AVR. RESULTS: Delirium occurred in 21 (23%) patients, within the first three postoperative days in 95% (20/21) of the cases. Delirium incidence was lower in TAVR (13/66 = 20%) than SAVR (8/27 = 30%) patients, but this difference was not statistically significant (p = .298). Patients with delirium had lower baseline cognitive performance (median MMSE score 27.0 ± 3.0 vs 28.0 ± 3.0, p = .029), lower performance in IADL (7.0 vs 8.0, p = .038), and higher STS risk scores (4.7 ± 2.7 vs 2.9 ± 2.3, p = .020). In multivariate analyses, patients with intermediate (score > 3 to ≤8) and high (score > 8) STS risk scores had 4.3 (95%CI 1.2-15.1, p = .025) and 16.5 (95%CI 2.0-138.2, p = .010), respectively, higher odds of incident delirium compared to patients with low (score ≤ 3) STS risk scores. At 3-month follow-up (N = 77), patients with delirium still had lower MMSE score (27.0 ± 8.0 vs 28.0 ± 2.0, p = .007) but this difference did not remain significant once adjusting for baseline MMSE (ß-coefficient 1.11, 95%CI [- 3.03-0.80], p = .248). CONCLUSIONS: Delirium occurred in about one in five older patients undergoing AVR, almost essentially within the first three postoperative days. Beside cognitive performance, STS risk score could enhance the identification of high-risk older patients to better target preventative interventions.


Assuntos
Delírio , Implante de Prótese de Valva Cardíaca , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Cognição , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Incidência , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
18.
Eur Respir J ; 57(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33692120

RESUMO

INTRODUCTION: Hospitalised patients with coronavirus disease 2019 (COVID-19) as a result of SARS-CoV-2 infection have a high mortality rate and frequently require noninvasive respiratory support or invasive ventilation. Optimising and standardising management through evidence-based guidelines may improve quality of care and therefore patient outcomes. METHODS: A task force from the European Respiratory Society and endorsed by the Chinese Thoracic Society identified priority interventions (pharmacological and non-pharmacological) for the initial version of this "living guideline" using the PICO (population, intervention, comparator, outcome) format. The GRADE approach was used for assessing the quality of evidence and strength of recommendations. Systematic literature reviews were performed, and data pooled by meta-analysis where possible. Evidence tables were presented and evidence to decision frameworks were used to formulate recommendations. RESULTS: Based on the available evidence at the time of guideline development (20 February, 2021), the panel makes a strong recommendation in favour of the use of systemic corticosteroids in patients requiring supplementary oxygen or ventilatory support, and for the use of anticoagulation in hospitalised patients. The panel makes a conditional recommendation for interleukin (IL)-6 receptor antagonist monoclonal antibody treatment and high-flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. The panel make strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir. Conditional recommendations are made against the use of azithromycin, hydroxychloroquine combined with azithromycin, colchicine, and remdesivir, in the latter case specifically in patients requiring invasive mechanical ventilation. No recommendation was made for remdesivir in patients requiring supplemental oxygen. Further recommendations for research are made. CONCLUSION: The evidence base for management of COVID-19 now supports strong recommendations in favour and against specific interventions. These guidelines will be regularly updated as further evidence becomes available.


Assuntos
COVID-19/terapia , Hospitalização , Corticosteroides/uso terapêutico , Adulto , Humanos , Metanálise como Assunto , Respiração Artificial , Revisões Sistemáticas como Assunto
19.
Nat Commun ; 12(1): 1720, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741934

RESUMO

Pulmonary arterial hypertension is a progressive fatal disease that is characterized by pathological pulmonary artery remodeling, in which endothelial cell dysfunction is critically involved. We herein describe a previously unknown role of endothelial angiocrine in pulmonary hypertension. By searching for genes highly expressed in lung microvascular endothelial cells, we identify inhibin-ß-A as an angiocrine factor produced by pulmonary capillaries. We find that excess production of inhibin-ß-A by endothelial cells impairs the endothelial function in an autocrine manner by functioning as activin-A. Mechanistically, activin-A induces bone morphogenetic protein receptor type 2 internalization and targeting to lysosomes for degradation, resulting in the signal deficiency in endothelial cells. Of note, endothelial cells isolated from the lung of patients with idiopathic pulmonary arterial hypertension show higher inhibin-ß-A expression and produce more activin-A compared to endothelial cells isolated from the lung of normal control subjects. When endothelial activin-A-bone morphogenetic protein receptor type 2 link is overdriven in mice, hypoxia-induced pulmonary hypertension was exacerbated, whereas conditional knockout of inhibin-ß-A in endothelial cells prevents the progression of pulmonary hypertension. These data collectively indicate a critical role for the dysregulated endothelial activin-A-bone morphogenetic protein receptor type 2 link in the progression of pulmonary hypertension, and thus endothelial inhibin-ß-A/activin-A might be a potential pharmacotherapeutic target for the treatment of pulmonary arterial hypertension.


Assuntos
Ativinas/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Hipertensão Pulmonar/metabolismo , Animais , Apoptose , Modelos Animais de Doenças , Endocitose , Células Endoteliais/metabolismo , Técnicas de Inativação de Genes , Humanos , Hipertensão Pulmonar/patologia , Hipóxia , Subunidades beta de Inibinas , Inibinas , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Hipertensão Arterial Pulmonar , Remodelação Vascular
20.
J Allergy Clin Immunol Pract ; 9(3): 1081-1088, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33685606

RESUMO

Five biologic medications are approved in the United States for the treatment of asthma that is not well controlled with other therapies. All target asthma with elevated type 2 inflammatory markers, such as elevated eosinophils, fractional exhaled nitric oxide, or total and specific IgE. Asthma severity, phenotype, age, biomarkers, treatment goals/outcomes, comorbid conditions, safety, and cost should all help guide the initial biologic choice. In addition, a shared decision-making process with the patient is needed to optimize adherence, with special attention to patient preference regarding outcomes, safety concerns, and medication administration options. After a biologic agent is initiated, sufficient time is needed to monitor efficacy and response. For patients who do not respond favorably, patient-, disease-, and medication-related factors should be considered and remedied, if possible. Persistent suboptimal responders necessitate a reexamination of asthma phenotype, biomarkers, and the suspected immune response pathways. For some patients, a change in biologic therapy or other therapeutic options may be warranted. In this review, we examine the clinical approach for choosing an initial biologic for the treatment of asthma, the assessment of response to biologics, and the process of troubleshooting and adjusting biologic treatment for those patients with suboptimal responses.


Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Eosinófilos , Humanos , Óxido Nítrico
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