The earliest thymic T cell progenitors sustain B cell and myeloid lineage potential.

The stepwise commitment from hematopoietic stem cells in the bone marrow to T lymphocyte-restricted progenitors in the thymus represents a paradigm for understanding the requirement for distinct extrinsic cues during different stages of lineage restriction from multipotent to lineage-restricted progenitors. However, the commitment stage at which progenitors migrate from the bone marrow to the thymus remains unclear. Here we provide functional and molecular evidence at the single-cell level that the earliest progenitors in the neonatal thymus had combined granulocyte-monocyte, T lymphocyte and B lymphocyte lineage potential but not megakaryocyte-erythroid lineage potential. These potentials were identical to those of candidate thymus-seeding progenitors in the bone marrow, which were closely related at the molecular level. Our findings establish the distinct lineage-restriction stage at which the T cell lineage-commitment process transits from the bone marrow to the remote thymus.

Association Between Serum Myostatin Levels, Hospital Mortality, and Muscle Mass and Strength Following ST-Elevation Myocardial Infarction.

AIM: This study aimed to evaluate the association between serum myostatin levels, hospital mortality, and muscle mass and strength following ST-segment elevation myocardial infarction (STEMI). METHODS: This was a prospective observational study. Within 48 hours of admission, bioelectrical impedance and handgrip strength were assessed and blood samples collected for myostatin evaluation. Hospital mortality was recorded. A multiple logistic regression model was also constructed, adjusted by parameters that exhibited significant differences in the univariate analysis, to evaluate the association between myostatin levels and hospital mortality. RESULTS: One hundred and two (102) patients were included: mean age was 60.5±10.6 years, 67.6% were male, and 6.9% died during hospital stay. Univariate analysis showed that patients with lower myostatin levels had higher mortality rates. Serum myostatin levels positively correlated with handgrip strength (r=0.355; p<0.001) and appendicular skeletal muscle mass index (r=0.268; p=0.007). Receiver operating characteristic (ROC) curve analysis revealed that lower myostatin levels were associated with hospital mortality at the <2.20 ng/mL cut-off. Multiple logistic regression showed that higher serum myostatin levels were associated with reduced hospital mortality when adjusted by ß blocker use (OR, 0.228; 95% CI, 0.054-0.974; p=0.046). CONCLUSIONS: Serum myostatin concentrations positively correlated with muscle mass and strength in STEMI patients. Further assessment of serum myostatin association with mortality should be conducted using a larger sample and assessing the additive value to the Global Registry of Acute Coronary Events (GRACE) or thrombolysis in myocardial infarction (TIMI) risk scores.

Canonical Notch signaling is dispensable for adult steady-state and stress myelo-erythropoiesis.

Although an essential role for canonical Notch signaling in generation of hematopoietic stem cells in the embryo and in thymic T-cell development is well established, its role in adult bone marrow (BM) myelopoiesis remains unclear. Some studies, analyzing myeloid progenitors in adult mice with inhibited Notch signaling, implicated distinct roles of canonical Notch signaling in regulation of progenitors for the megakaryocyte, erythroid, and granulocyte-macrophage cell lineages. However, these studies might also have targeted other pathways. Therefore, we specifically deleted, in adult BM, the transcription factor recombination signal-binding protein J κ (Rbpj), through which canonical signaling from all Notch receptors converges. Notably, detailed progenitor staging established that canonical Notch signaling is fully dispensable for all investigated stages of megakaryocyte, erythroid, and myeloid progenitors in steady state unperturbed hematopoiesis, after competitive BM transplantation, and in stress-induced erythropoiesis. Moreover, expression of key regulators of these hematopoietic lineages and Notch target genes were unaffected by Rbpj deficiency in BM progenitor cells.

Refractory myasthenia gravis: Characteristics of a portuguese cohort.

INTRODUCTION: Some myasthenia gravis (MG) patients are refractory to conventional treatments. METHODS: To describe the clinical features of refractory MG (RMG) and explore the association with human leukocyte antigen HLA-DRB1 alleles, a cohort study of 114 consecutive MG patients was performed. Patients were classified as RMG based on predefined criteria. RESULTS: Twenty-two patients were found to have RMG (19.3%). There were no differences between non-RMG and RMG patients with respect to sex, age of onset, abnormal 3-Hz repetitive nerve stimulation, anti-acetylcholine receptor antibody positivity, thymectomy, thymoma or thymic hyperplasia, and polyautoimmunity. HLA-DRB1*03 was more frequent in the non-RMG vs. control population (P = 3 × 10-6 ). The HLA-DRB1*13 allele was less frequent in non-RMG patients compared with controls (P = 0.002), and less frequent in the non-RMG group compared with the RMG group (P = 0.003). DISCUSSION: HLA-DRB1*03 was more common in non-RMG, and the HLA-DRB1*13 allele appeared to have a protective role, as reported previously in other autoimmune disorders. Muscle Nerve 60: 188-191, 2019.

Case report of recalcitrant allergic contact eczema successfully treated with teriflunomide.

Allergic contact dermatitis (ACD) is a type IV, delayed-type reaction caused by skin contact with low-molecular-weight organic chemicals and metal ions that activate antigen-specific T cells, primarily T-helper 1 (Th1), in a sensitized individual, leading to skin eczema.First-line treatments are based on avoidance of causal agents and topical corticosteroids/immunomodulators. In recalcitrant cases, chronic oral immunosuppressive agents may be used, but they may have serious adverse effects and do not address the immunological disfunction. We report a case of severe ACD, unresponsive to topical or oral immunosuppressive therapy, which resolved itself after treatment with teriflunomide (TF) 14 mg/daily used for multiple sclerosis. TF is a once-daily, oral selective and reversible dihydroorotate dehydrogenase inhibitor, revealing a new treatment option for ACD.

Repressor activity of the RpoS/σS-dependent RNA polymerase requires DNA binding.

The RpoS/σ(S) sigma subunit of RNA polymerase (RNAP) activates transcription of stationary phase genes in many Gram-negative bacteria and controls adaptive functions, including stress resistance, biofilm formation and virulence. In this study, we address an important but poorly understood aspect of σ(S)-dependent control, that of a repressor. Negative regulation by σ(S) has been proposed to result largely from competition between σ(S) and other σ factors for binding to a limited amount of core RNAP (E). To assess whether σ(S) binding to E alone results in significant downregulation of gene expression by other σ factors, we characterized an rpoS mutant of Salmonella enterica serovar Typhimurium producing a σ(S) protein proficient for Eσ(S) complex formation but deficient in promoter DNA binding. Genome expression profiling and physiological assays revealed that this mutant was defective for negative regulation, indicating that gene repression by σ(S) requires its binding to DNA. Although the mechanisms of repression by σ(S) are likely specific to individual genes and environmental conditions, the study of transcription downregulation of the succinate dehydrogenase operon suggests that σ competition at the promoter DNA level plays an important role in gene repression by Eσ(S).

FLT3 expression initiates in fully multipotent mouse hematopoietic progenitor cells.

Lymphoid-primed multipotent progenitors with down-regulated megakaryocyte-erythroid (MkE) potential are restricted to cells with high levels of cell-surface FLT3 expression, whereas HSCs and MkE progenitors lack detectable cell-surface FLT3. These findings are compatible with FLT3 cell-surface expression not being detectable in the fully multipotent stem/progenitor cell compartment in mice. If so, this process could be distinct from human hematopoiesis, in which FLT3 already is expressed in multipotent stem/progenitor cells. The expression pattern of Flt3 (mRNA) and FLT3 (protein) in multipotent progenitors is of considerable relevance for mouse models in which prognostically important Flt3 mutations are expressed under control of the endogenous mouse Flt3 promoter. Herein, we demonstrate that mouse Flt3 expression initiates in fully multipotent progenitors because in addition to lymphoid and granulocyte-monocyte progenitors, FLT3(-) Mk- and E-restricted downstream progenitors are also highly labeled when Flt3-Cre fate mapping is applied.

GATA3 is redundant for maintenance and self-renewal of hematopoietic stem cells.

GATA3 has been identified as a master regulator of T helper cells, as well as being important for early thymic progenitors and T-cell commitment. However, Gata3 expression initiates already at the hematopoietic stem cell (HSC) level, implicating a potential role also in the regulation of HSCs. Herein we used a conditional Gata3 knockout strategy in which Gata3 expression was completely deleted from the earliest stage of embryonic hematopoietic development after emergence of HSCs from hemogenic endothelium. Through a detailed analysis of HSCs at the phenotypic and functional level, we demonstrate that steady-state levels of HSCs are normal in Gata3(fl/fl)Vav-Cre(tg/+) mice. Moreover, through long-term primary and secondary transplantation experiments, we also unequivocally demonstrate that Gata3 has a redundant role in post-transplantation HSC self-renewal.

Impact of delaying botulinum toxin treatment in patients with migraine during the COVID-19 pandemic.

BACKGROUND: Due to coronavirus disease 2019 (COVID-19) pandemic response measures, the administration of botulinum toxin (BTX) was delayed for many patients during the first lockdown period in Portugal. OBJECTIVES: To review the impact of postponing BTX treatment on migraine control. METHODS: This was a retrospective, single-center study. Patients with chronic migraine who had done at least three previous BTX cycles and were considered responders were included. The patients were divided into two groups, one that has had their treatment delayed (group P), and one that has not (controls). The Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) protocol was used. Migraine-related data were obtained at baseline and at three subsequent visits. RESULTS: The present study included two groups, group P (n = 30; 47.0 ± 14.5 years; 27 females, interval baseline -1st visit: 5.5 [4.1-5.8] months) and the control group (n = 6; 57.7 ± 13.2 years; 6 females; interval baseline-1st visit 3.0 [3.0-3.2] months). No difference between the groups was present at baseline. When compared to baseline, the number of days/month with migraine (5 [3-6.2] vs. 8 [6-15] p < 0.001), days using triptans/month (2.5 [0-6] vs. 3 [0-8], p = 0.027) and intensity of pain (7 [5.8-10] vs. 9 [7-10], p = 0.012) were greater in the first visit for group P, while controls did not present a significant variation. The worsening of migraine-related indicators decreased in the following visits; however, even in the third visit, it had not returned to baseline. Correlations were significant between the delayed time to treatment and the increase in days/month with migraines at the first visit after lockdown (r = 0.507; p = 0.004). CONCLUSIONS: There was a deterioration of migraine control after postponed treatments, with a direct correlation between the worsening of symptoms and the number of months that the treatment was delayed.

ANTECEDENTES: Devido às medidas de resposta à pandemia de coronavirus disease 2019 (covid-19), a administração de toxina botulínica (TXB) foi adiada para muitos pacientes durante o primeiro confinamento em Portugal. OBJETIVOS: Avaliar o impacto do adiamento do tratamento com TXB no controle da enxaqueca. MéTODOS: Estudo retrospectivo unicêntrico. Foram incluídos pacientes com enxaqueca crônica com pelo menos três ciclos prévios de TXB e que tenham sido considerados respondedores. Os pacientes foram divididos em dois grupos, sendo um com atraso do tratamento (grupo P) e outro sem atraso (controles). O protocolo Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) foi utilizado. Dados clínicos relacionados com a enxaqueca foram obtidos na consulta inicial (T0) e nas três consultas subsequentes (T1­3). RESULTADOS: O presente estudo incluiu dois grupos, o grupo P (n = 30; 47,0 ± 14,5 anos; 27 mulheres, intervalo T0-1ª visita: 5,5 [4,1­5,8] meses) e o grupo controle (n = 6; 57,7 ± 13,2 anos; 6 mulheres; intervalo T0­1ª visita 3,0 [3,0­3,2] meses). Os grupos não apresentavam nenhuma diferença no início do estudo. Quando comparado à T0, o número de dias/mês com enxaqueca (5 [3­6,2] vs. 8 [6­15], p < 0,001), dias usando triptanos/mês (2,5 [0­6] vs. 3 [0­8], p = 0,027) e intensidade da dor (7 [5,8­10] vs. 9 [7­10], p = 0,012) foram maiores na primeira visita no grupo P, não apresentando os controles variação significativa. A piora dos indicadores relacionados com a enxaqueca diminuiu nas visitas seguintes; porém, mesmo na terceira visita, ainda não haviam retornado ao basal. As correlações foram significativas entre o atraso do tratamento e o aumento de dias/mês com enxaqueca na primeira consulta após o confinamento (r = 0,507; p = 0,004). CONCLUSãO: Houve piora clínica da enxaqueca após o adiamento do tratamento em correlação direta com a duração do atraso.

Primary Central Nervous System Lymphoma Complicated by Cerebral Venous Sinus Thrombosis: A Case Report.

Central nervous system (CNS) lymphoma is a rare and aggressive primary neoplasm that comprises a small proportion of brain tumours and non-Hodgkin lymphomas. We present a case report of a 64-year-old woman with CNS lymphoma, who exhibited cognitive changes, weight loss and neurological symptoms. Imaging scans revealed multiple lesions in the brain and thrombosis in the venous sinuses. A diagnosis of diffuse large B-cell lymphoma of the CNS was confirmed through histological examination. The patient underwent treatment with corticosteroids and chemotherapy, but experienced clinical deterioration with thrombocytopenia and disease progression. Despite efforts to manage complications and provide targeted therapy, the patient passed away. Primary CNS lymphoma typically responds well to chemotherapy, and prognostic factors such as age and functional status play a significant role in patient outcomes. However, complications such as thromboembolism pose challenges during treatment due to the hypercoagulable state induced by chemotherapy agents. The pathophysiology of thromboembolic events in the context of malignancy remains uncertain but may involve direct tumour compression, vascular invasion and alterations in coagulation factors. The diagnostic process for CNS lymphoma can be complex, and the information obtained from cerebrospinal fluid analysis, including flow cytometry, may be limited in cases with low cell counts. Ongoing research exploring genetic tests and biomarkers shows promise for improving diagnostic accuracy in such cases. This case underscores the need for comprehensive management strategies that address both the neoplasm and its associated complications, to optimise patient outcomes. LEARNING POINTS: Primary CNS lymphoma is a rare primary neoplasm, being even rarer in immunocompetent patients.In 25% of all cases of CNS lymphoma, it is complicated by cerebral venous thromboembolism.Leptomeningeal spread can occur with or without MRI evidence and is diagnosed with cerebrospinal fluid (CSF) flow cytometry. Age and functional status are important prognostic factors.

Levodopa-Induced Pseudopheochromocytoma.

Pseudopheochromocytoma is a pathological condition presenting with paroxysmal hypertension with normal or moderate elevation in catecholamines and metanephrine levels, but no evidence of a tumoural cause. Imaging studies and I-123 metaiodobenzylguanidine scintigraphy are essential for exclusion of pheocromocytoma. We describe a case of pseudopheochromocytoma related to levodopa in a patient with paroxysmal hypertension, headache, sweating, palpitations and increased plasmatic and urinary metanephrine levels, without adrenal or extra-adrenal tumour. The beginning of the patient's clinical symptoms coincided with the initiation of the levodopa treatment and the complete resolution of the symptoms occurred after the discontinuation of levodopa. LEARNING POINTS: Pseudopheochromocytoma and pheochromocytoma may have the same clinical and laboratorial presentation but different aetiologies.The diagnosis of pseudopheochromocytoma is based on paroxysmal hypertension with normal or increased plasma and urine levels of catecholamines or metanephrines after exclusion of a tumoural process.The pseudopheochromocytoma may be associated with levodopa, alone or in combination with other drugs that are likely to interfere with dopamine or catecholamine metabolism.

Characterization of a late-onset multiple sclerosis Portuguese cohort.

BACKGROUND: Late-onset multiple sclerosis (LOMS) is defined as the onset of symptoms above 50 years, corresponding to an increasingly recognized subset of MS. This study aimed at comparing demographic and clinical data of patients with LOMS to those of early-onset MS (EOMS) from a Portuguese cohort. METHODS: Retrospective chart review of an MS cohort from a Portuguese tertiary center. RESULTS: From 746 patients with MS (61.7% female), we identified 39 cases with presentation after 50 years of age (22 males and 17 females), corresponding to 5.3%. The mean age at onset was 55.4 (±5.0) for LOMS and 29.5 (±8.9) for EOMS. There was no significant difference in disease duration. The most common type was relapsing-remitting MS, accounting for 51.5% and 83.9% of LOMS and EOMS patients, respectively. Primary-progressive MS (PPMS) was significantly more represented in the LOMS group (41.0%) (p < 0.01). The median EDSS was significantly higher in the LOMS group (4.75, 0.0-7.5) when compared to the EOMS group (2.0, 0.0-9,0). The most frequent presenting feature was myelitis in both LOMS (48.7%) and EOMS patients (47.4%), resulting in significantly higher EDSS (p = 0.003). CONCLUSIONS: LOMS is associated with higher EDSS when considering the same disease duration, translating into increased disability.

Interim FDG18-PET SUVmax Variation Adds Prognostic Value to Deauville 5-Point Scale in the Identification of Patients with Ultra-High-Risk Diffuse Large B Cell Lymphoma.

INTRODUCTION: Interim response evaluation by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (iPET) in diffuse large B cell lymphoma (DLBCL) could be important to rule out disease progression and has been suggested to be predictive of survival. However, treatment guidance by iPET is not yet recommended for DLBCL in clinical practice. We aimed to compare the predictive value of iPET when utilizing the visual Deauville 5-point scale (DS) and the semiquantitative variation of maximum standardized uptake value (ΔSUVmax). MATERIALS AND METHODS: We included 85 patients diagnosed with DLBCL and uniformly treated with standard protocols. iPET with DS of 1-3 and/or ΔSUVmax ≥66% was defined as negative. Univariable and multivariable Cox regression analyses were performed to determine the independent factors affecting progression free survival (PFS) or overall survival (OS) and to estimate PFS and OS. RESULTS: iPET positivity, measured by DS or ΔSUVmax, showed predictive value of disease refractoriness, improved by combining DS and ΔSUVmax. After a median follow-up of 50.1 months, iPET was an independent predictor for both PFS and OS when interpreted by DS, but only for PFS by ΔSUVmax. Combined visual and semiquantitative analysis (D4-5 & ΔSUVmax<66%) was an independent predictor of PFS and OS, and allowed to identify an ultra-high-risk subgroup of patients with very dismal outcome, increasing the discriminating capacity for iPET. CONCLUSION: Our study suggests that combined DS and ΔSUVmax in iPET assessment predicts refractory disease and distinguishes ultra-high-risk DLBCL patients with a very dismal prognosis, who may benefit from PET-guided therapy adjustment.

Pd(II) and Pt(II) Trinuclear Chelates with Spermidine: Selective Anticancer Activity towards TNBC-Sensitive and -Resistant to Cisplatin.

Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer and constitutes 10-20% of all breast cancer cases. Even though platinum-based drugs such as cisplatin and carboplatin are effective in TNBC patients, their toxicity and development of cancer drug resistance often hamper their clinical use. Hence, novel drug entities with improved tolerability and selectivity profiles, as well as the ability to surpass resistance, are needed. The current study focuses on Pd(II) and Pt(II) trinuclear chelates with spermidine (Pd3Spd2 and Pt3Spd2) for evaluating their antineoplastic activity having been assessed towards (i) cisplatin-resistant TNBC cells (MDA-MB-231/R), (ii) cisplatin-sensitive TNBC cells (MDA-MB-231) and (iii) non-cancerous human breast cells (MCF-12A, to assess the cancer selectivity/selectivity index). Additionally, the complexes' ability to overcome acquired resistance (resistance index) was determined. This study revealed that Pd3Spd2 activity greatly exceeds that displayed by its Pt analog. In addition, Pd3Spd2 evidenced a similar antiproliferative activity in both sensitive and resistant TNBC cells (IC50 values 4.65-8.99 µM and 9.24-13.34 µM, respectively), with a resistance index lower than 2.3. Moreover, this Pd compound showed a promising selectivity index ratio: >6.28 for MDA-MB-231 cells and >4.59 for MDA-MB-231/R cells. Altogether, the data presently gathered reveal Pd3Spd2 as a new, promising metal-based anticancer agent, which should be further explored for the treatment of TNBC and its cisplatin-resistant forms.

Anti-NMDAr Encephalitis and COVID-19 in a Patient With Systemic pANCA-Vasculitis and Recurrent Varicella Zoster Infection.

Introduction: There is a complex interplay between systemic autoimmunity, immunosuppression, and infections. Any or all of these can result in neurologic manifestations, requiring diligence on the part of neurologists. Case report: We herein report a case of a patient on immunosuppressive treatment for a vasculitis that resulted in zoster meningoencephalitis. This was further complicated by the development of anti-NMDAr encephalitis, the etiology of which is undetermined and further discussed in this paper. The patient eventually developed COVID-19 during hospitalization, succumbing to the respiratory infection. Conclusion: This case emphasizes that post-infectious autoimmune disorders are becoming increasingly recognized and that they should still be considered in patients who are on immunosuppression. Practitioners should be aware of the complex relationship between autoimmunity and immunosuppression and consider both throughout the disease course.

Preneoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma.

Normal cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B lymphocytes before lymphoma remains uncertain. We sequenced multiple stages of the B lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of the high prevalence of mutated MYD88. We observed similar accumulation of random mutations in B lineages from both cohorts and unexpectedly found MYD88L265P in normal precursor and mature B lymphocytes from patients with lymphoma. We uncovered genetic and transcriptional pathways driving malignant transformation and leveraged these to model lymphoplasmacytic lymphoma in mice, based on mutated MYD88 in B cell precursors and BCL2 overexpression. Thus, MYD88L265P is a preneoplastic event, which challenges the current understanding of lymphomagenesis and may have implications for early detection of B cell lymphomas.

FLT3 receptor and ligand are dispensable for maintenance and posttransplantation expansion of mouse hematopoietic stem cells.

Originally cloned from hematopoietic stem cell (HSC) populations and its ligand being extensively used to promote ex vivo HSC expansion, the FMS-like tyrosine kinase 3 (FLT3; also called FLK2) receptor and its ligand (FL) were expected to emerge as an important physiologic regulator of HSC maintenance and expansion. However, the role of FLT3 receptor and ligand in HSC regulation remains unclear and disputed. Herein, using Fl-deficient mice, we establish for the first time that HSC expansion in fetal liver and after transplantation is FL independent. Because previous findings in Flk2(-/-) mice were compatible with an important role of FLT3 receptor in HSC regulation and because alternative ligands might potentially interact directly or indirectly with FLT3 receptor, we here also characterized HSCs in Flk2(-/-) mice. Advanced phenotypic as well as functional evaluation of Flk2(-/-) HSCs showed that the FLT3 receptor is dispensable for HSC steady-state maintenance and expansion after transplantation. Taken together, these studies show that the FLT3 receptor and ligand are not critical regulators of mouse HSCs, neither in steady state nor during fetal or posttransplantation expansion.

[Asthma Management and Control in Portuguese Speaking Countries]. / Gestão e Controlo da Asma em Países de Expressão Portuguesa.

INTRODUCTION: Asthma affects more than 339 million people worldwide. In the Community of Portuguese Speaking Countries, in 2016, its prevalence ranged from 9.5% (Portugal) to 3.91% (Brazil). Chronic disease management programs aim to improve the health status of patients with chronic disease and reduce associated costs. The objective of this study is to identify models of asthma asthma 'management and control' that are that are implemented in the Community of Portuguese Speaking Countries (CPLP), and analyse them through the integrated disease management model. MATERIAL AND METHODS: A rapid review of the PubMed indexed scientific literature and grey literature on 'management and control of asthma' in the countries of the Community of Portuguese-Speaking Countries was carried out. RESULTS: Portugal, Brazil and Mozambique presented publications on 'management and control of asthma', at different stages of implementation. Clinical management and organization and service delivery are the dimensions of integrated disease management most addressed in publications. DISCUSSION: The implementation of asthma management and control programs is influenced by health systems, care delivery structures, and the surrounding political and social environment. The dimensions of funding and information systems are the most difficult to implement given the degree of economic, social and technological development of most countries under study. CONCLUSION: Only Portugal, Brazil and Mozambique adopted asthma integrated disease management as the main form of asthma management and control. The programs developed by these countries can constitute a model for asthma integrated disease management in the other countries under study.

Introdução: A asma atinge mais de 339 milhões de pessoas mundialmente. Na Comunidade dos Países de Língua Portuguesa, em 2016, a sua prevalência variou entre 9,15% (Portugal) e 3,91% (Brasil). Os programas de gestão da doença crónica pretendem melhorar o estado de saúde de doentes com doença crónica e reduzir os custos associados. O objetivo deste estudo é identificar modelos de 'gestão e controlo da asma' implementados na Comunidade dos Países de Língua Portuguesa, analisando-os através do modelo de gestão integrada de doença.Material e Métodos: Realizou-se uma revisão rápida da literatura científica indexada na PubMed, e de literatura cinzenta sobre 'gestão e controlo da asma' nos países da Comunidade dos Países de Língua Portuguesa.Resultados: Portugal, Brasil e Moçambique apresentaram publicações sobre 'gestão e controlo da asma', em diferentes fases de implementação dos programas. A gestão clínica e organização e prestação de cuidados são as dimensões mais abordados nas publicações.Discussão: A implementação de programas de gestão e controlo da asma é influenciada pelos sistemas de saúde, estruturas de prestação de cuidados em que se inserem, meio político e social envolventes. As dimensões do financiamento e dos sistemas de informação são as mais difíceis de implementar, dado o desenvolvimento económico, social e tecnológico da maioria dos países em estudo.Conclusão: Apenas Portugal, Brasil e Moçambique adotaram a gestão integrada de doença da asma como principal forma de gestão e controlo da asma. Os programas desenvolvidos por estes países podem servir de modelo nos restantes países em estudo.