Mathematical model describing CoViD-19 in São Paulo, Brazil - evaluating isolation as control mechanism and forecasting epidemiological scenarios of release.

In São Paulo, Brazil, the first case of coronavirus disease 2019 (CoViD-19) was confirmed on 26 February, the first death due to CoViD-19 was registered on 16 March, and on 24 March, São Paulo implemented the isolation of persons in non-essential activities. A mathematical model was formulated based on non-linear ordinary differential equations considering young (60 years old or less) and elder (60 years old or more) subpopulations, aiming to describe the introduction and dissemination of the new coronavirus in São Paulo. This deterministic model used the data collected from São Paulo to estimate the model parameters, obtaining R0 = 6.8 for the basic reproduction number. The model also allowed to estimate that 50% of the population of São Paulo was in isolation, which permitted to describe the current epidemiological status. The goal of isolation implemented in São Paulo to control the rapid increase of the new coronavirus epidemic was partially succeeded, concluding that if isolation of at least 80% of the population had been implemented, the collapse in the health care system could be avoided. Nevertheless, the isolated persons must be released one day. Based on this model, we studied the potential epidemiological scenarios of release by varying the proportions of the release of young and elder persons. We also evaluated three different strategies of release: All isolated persons are released simultaneously, two and three releases divided in equal proportions. The better scenarios occurred when young persons are released, but maintaining elder persons isolated for a while. When compared with the epidemic without isolation, all strategies of release did not attain the goal of reducing substantially the number of hospitalisations due to severe CoViD-19. Hence, we concluded that the best decision must be postponing the beginning of the release.

Fluticasone/formoterol dry powder versus budesonide/formoterol in adults and adolescents with uncontrolled or partly controlled asthma.

UNLABELLED: This 12-week study compared the efficacy and safety of a fixed combination of fluticasone propionate plus formoterol (FL/F) 250/12 µg b.i.d. administered via a dry powder inhaler (DPI) (Libbs Farmacêutica, Brazil) to a combination of budesonide plus formoterol (BD/F) 400/12 µg b.i.d. After a 2-week run-in period (in which all patients were treated exclusively with budesonide plus formoterol), patients aged 12-65 years of age (N = 196) with uncontrolled asthma were randomized into an actively-controlled, open-labeled, parallel-group, multicentre, phase III study. The primary objective was to demonstrate non-inferiority, measured by morning peak expiratory flow (mPEF). The non-inferiority was demonstrated. A statistically significant improvement from baseline was observed in both groups in terms of lung function, asthma control, and the use of rescue medication. FL/F demonstrated a statistical superiority to BD/F in terms of lung function (FEV(1)) (p = 0.01) and for asthma control (p = 0.02). Non-significant between-group differences were observed with regards to exacerbation rates and adverse events. In uncontrolled or partly controlled asthma patients, the use of a combination of fluticasone propionate plus formoterol via DPI for 12-weeks was non-inferior and showed improvements in FEV(1) and asthma control when compared to a combination of budesonide plus formoterol. ( CLINICAL TRIAL NUMBER: ISRCTN60408425).

Inflammatory cell mapping of the respiratory tract in fatal asthma.

BACKGROUND: The site and distribution of inflammation in the airways of asthmatic patients has been largely investigated. Inflammatory cells are distributed in both large and small airways in asthma. It has been demonstrated that distal lung inflammation in asthma may significantly contribute to the pathophysiology of the disease. The upper airways have also been implicated in the overall asthmatic inflammation. Although it is now accepted that lung inflammation is not restricted to the intrapulmonary airways in asthma, little is known about cell distribution in the other lung compartments and their relation to the intrapulmonary airways. OBJECTIVE: We aimed to map the inflammatory process in fatal asthma (FA), from the upper airways to the lung parenchyma. METHODS: Eosinophil, neutrophil, mast cell and lymphocyte content were determined in nasal mucosa, the trachea, intrapulmonary airways and parenchyma (peribronchiolar and distal) of 20 patients with FA and 10 controls. RESULTS: Eosinophil content was higher in all studied areas in FA compared with controls (P<0.02). Mast cell content was higher in the outer area of larger airways, small membranous bronchioles and in peribronchiolar parenchyma of FA compared with controls (P<0.04). CD3+, CD4+and CD20+cells showed increased content in FA intrapulmonary airways compared with controls (P<0.05). There was a positive correlation between CD4+cell content in nasal mucosa and larger airways in asthmatics. Increased neutrophil content was observed only in peribronchiolar parenchyma of FA (P=0.028). CONCLUSION: Eosinophils present a widespread distribution within the respiratory tract in FA, from the nasal mucosa to the distal lung. The outer wall of small membranous bronchioles is the main site of inflammatory changes in FA. There is a localized distribution of alveolar inflammation at the peribronchiolar region for mast cells and neutrophils. Our findings provide further evidence of the importance of the lung periphery in the pathophysiology of FA.

Inflamação do parênquima pulmonar na asma e sua relação com as vias aéreas / Pulmonary parenchyma inflammation in asthma

A inflamação da asma não está limitada às vias aéreas e pode comprometer também o parênquima pulmonar periférico, no entanto, não há estudos na literatura que enfoquem a participação do parênquima pulmonar na asma. Objetivo: Caracterizar o infiltrado inflamatótrio do parênquima peribronquiolar e distal em vítimas de asma fatal, comparando-o ao de outras regiões de vias aéreas e a de tecido pulmonar de não asmáticos. Fragementos de tecido pulmonar obtidos de 20 pacientes com asma fatal e 10 controles, necropsiados no Serviço de verificacão de óbito da capital - São Paulo, foram submetidos a estudo de imuno-histoquímica e marcados com anticorpos anti-proteína básica principal (eosinófilos), anti-triptase (mastócitos), anti-elastase neutrofílica (neutrófilos) e anti-marcadores de superfície de linfócitos (CD3, CD$, CD* e CD20). Foram determinadas as densidades celulares no parênquima pulmonar periférico peribronquiolar e distal e nas áreas interna e externa das vias aéreas de grande e de pequeno calibre. Resultados: A densidade de eosinófilos foi significativamente maior nas duas regiões do parênquima pulmonar de asmáticos comparados aos controles, bem como as vias aéreas (p<0,02). Nos pacientes asmáticos a densidade eosinófilica se mostrou menos no parênquima distal em relação à da área interna da via aérea grande apenas (p<0,01). A densidade dos mastócitos foi maior no parênquima peribronquiolar bem como na área externa das vias aéreas de grande e de pequeno calibre de asmáticos comparados aos controles (p<0.04). Diferenças significativas quanto à densidade de linfócitos se restringiram às vias aéreas de asmáticos comparadas as de controles. Maior densidade de neutrófilos foi observada apenas no parênquima pulmonar de asmáticos (p=0.029). Conclusões: O parênquima pulmonar participa do processo inflamatório na asma fatal com aumento de células efetoras (mastócitos, neutrófilos e eosinófilos). A área externa da via aérea foi a região que melhor diferenciou o asmáticodo controle e com o maior número de diferenças significativas. A inflamação do parênquima peribronquiolar, associado ao da área externa da via áerea pequena, reforça o papel do pulmão distal na patofisiologia da asma.