Saliva as a non-invasive specimen for COPD assessment.

BACKGROUND: People with COPD have been reported to bear a distinct airway microbiota from healthy individuals based on bronchoalveolar lavage (BAL) and sputum samples. Unfortunately, the collection of these samples involves relatively invasive procedures and is resource-demanding, limiting its regular use. Non-invasive samples from the upper airways could constitute an interesting alternative, but its relationship with COPD is still underexplored. We examined the merits of saliva to identify the typical profile of COPD oral bacteria and test its association with the disease. METHODS: Outpatients with COPD and age-sex matched healthy controls were recruited and characterised based on clinical parameters and 16S rRNA profiling of oral bacteria. A clustering analysis based on patients' oral bacteria beta-diversity and logistic regressions were performed to evaluate the association between oral bacteria composition and COPD. RESULTS: 128 individuals participated (70 patients and 58 controls). Differential abundance analyses showed differences in patients comparable to the ones previously observed in samples from the lower respiratory tract, i.e., an increase in Proteobacteria (particularly Haemophilus) and loss of microbiota diversity. An unsupervised clustering analysis separated patients in two groups based on microbiota composition differing significantly in the frequency of patients hospitalized due to severe acute exacerbation of COPD (AECOPD) and in the frequency of GOLD D patients. Furthermore, a low frequency of Prevotella was associated with a significantly higher risk of recent severe AECOPD and of being GOLD D. CONCLUSION: Salivary bacteria showed an association with COPD, particularly with severe exacerbations, supporting the use of this non-invasive specimen for future studies of heterogeneous respiratory diseases like COPD.

COPD profiles and treatable traits using minimal resources: identification, decision tree and stability over time.

BACKGROUND AND OBJECTIVE: Profiles of people with chronic obstructive pulmonary disease (COPD) often do not describe treatable traits, lack validation and/or their stability over time is unknown. We aimed to identify COPD profiles and their treatable traits based on simple and meaningful measures; to develop and validate a decision tree and to explore profile stability over time. METHODS: An observational, prospective study was conducted. Clinical characteristics, lung function, symptoms, impact of the disease (COPD Assessment Test-CAT), health-related quality of life, physical activity, lower-limb muscle strength and functional status were collected cross-sectionally and a subsample was followed-up monthly over six months. A principal component analysis and a clustering procedure with k-medoids were applied to identify profiles. A decision tree was developed and validated cross-sectionally. Stability was explored over time with the ratio between the number of timepoints that a participant was classified in the same profile and the total number of timepoints (i.e., 6). RESULTS: 352 people with COPD (67.4 ± 9.9 years; 78.1% male; FEV1 = 56.2 ± 20.6% predicted) participated and 90 (67.6 ± 8.9 years; 85.6% male; FEV1 = 52.1 ± 19.9% predicted) were followed-up. Four profiles were identified with distinct treatable traits. The decision tree included CAT (< 18 or ≥ 18 points); age (< 65 or ≥ 65 years) and FEV1 (< 48 or ≥ 48% predicted) and had an agreement of 71.7% (Cohen's Kappa = 0.62, p < 0.001) with the actual profiles. 48.9% of participants remained in the same profile whilst 51.1% moved between two (47.8%) or three (3.3%) profiles over time. Overall stability was 86.8 ± 15%. CONCLUSION: Four profiles and treatable traits were identified with simple and meaningful measures possibly available in low-resource settings. A decision tree with three commonly used variables in the routine assessment of people with COPD is now available for quick allocation to the identified profiles in clinical practice. Profiles and treatable traits may change over time in people with COPD hence, regular assessments to deliver goal-targeted personalised treatments are needed.

Functional Status Following Pulmonary Rehabilitation: Responders and Non-Responders.

The 6 min walking test (6MWT) has been largely studied. Less is, however, known about responders and non-responders to pulmonary rehabilitation (PR) in other meaningful activities. We explored responders and non-responders and the predictors of response to PR in the 1 min sit-to-stand test (1 min STS) and the 6MWT and compared both measures in classifying responders. An observational study was conducted with 121 people with chronic obstructive pulmonary disease (COPD). The functional status was assessed before and after PR. Baseline differences between responders and non-responders were tested with Mann-Whitney U, chi-square, or Fisher exact tests. Predictors were explored with binary logistic regressions. Agreement between both measures was assessed with chi-square, Cohen's kappa, and McNemar tests. There were 54.5% and 57.0% of responders in the 1 min STS and the 6MWT, respectively. The proportion of responders was significantly different (p = 0.048), with a small agreement between the measures (kappa = 0.180; p = 0.048). The baseline 6MWT was the only significant predictor of response in the 6MWT (OR = 0.995; pseudo-r2 = 0.117; p < 0.001). No significant predictors were found for the 1 min STS. A large number of non-responders in terms of functional status exist. The 1 min STS and the 6MWT should not be used interchangeably. Future studies should explore the added benefit of personalizing PR to this outcome and investigate other potential predictors.

Evaluation of the genetic risk for COVID-19 outcomes in COPD and differences among worldwide populations.

BACKGROUND: Populations seem to respond differently to the global pandemic of severe acute respiratory syndrome coronavirus 2. Recent studies show individual variability in both susceptibility and clinical response to COVID-19 infection. People with chronic obstructive pulmonary disease (COPD) constitute one of COVID-19 risk groups, being already associated with a poor prognosis upon infection. This study aims contributing to unveil the underlying reasons for such prognosis in people with COPD and the variability in the response observed across worldwide populations, by looking at the genetic background as a possible answer to COVID-19 infection response heterogeneity. METHODS: SNPs already associated with susceptibility to COVID-19 infection (rs286914 and rs12329760) and severe COVID-19 with respiratory failure (rs657152 and rs11385942) were assessed and their allelic frequencies used to calculate the probability of having multiple risk alleles. This was performed on a Portuguese case-control COPD cohort, previously clinically characterized and genotyped from saliva samples, and also on worldwide populations (European, Spanish, Italian, African, American and Asian), using publicly available frequencies data. A polygenic risk analysis was also conducted on the Portuguese COPD cohort for the two mentioned phenotypes, and also for hospitalization and survival to COVID-19 infection. FINDINGS: No differences in genetic risk for COVID-19 susceptibility, hospitalization, severity or survival were found between people with COPD and the control group (all p-values > 0.01), either considering risk alleles individually, allelic combinations or polygenic risk scores. All populations, even those with European ancestry (Portuguese, Spanish and Italian), showed significant differences from the European population in genetic risk for both COVID-19 susceptibility and severity (all p-values < 0.0001). CONCLUSION: Our results indicate a low genetic contribution for COVID-19 infection predisposition or worse outcomes observed in people with COPD. Also, our study unveiled a high genetic heterogeneity across major world populations for the same alleles, even within European sub-populations, demonstrating the need to build a higher resolution European genetic map, so that differences in the distribution of relevant alleles can be easily accessed and used to better manage diseases, ultimately, safeguarding populations with higher genetic predisposition to such diseases.

Construct validity of the brief physical activity assessment tool for clinical use in COPD.

INTRODUCTION: Low physical activity (PA) levels are associated with poor health-related outcomes in Chronic Obstructive Pulmonary Disease (COPD). Thus, PA should be routinely assessed in clinical practice. OBJECTIVES: This study assessed the construct validity of the Brief Physical Activity Assessment Tool (BPAAT) for clinical use in COPD and explored differences in age, sex and COPD grades. METHODS: After linguistic adaptation of the tool to Portuguese, 110 patients (66.4 ± 9.6yrs, 72.7% male, FEV1  = 59.3 ± 25.5%predicted) completed the BPAAT and received an accelerometer. The BPAAT includes two questions assessing the weekly frequency and duration of vigorous- and moderate-intensity PA/walking, classifying individuals as insufficiently or sufficiently active. The BPAAT was correlated with accelerometry (moderate PA, MPA = 1952-5724 counts-per-min [CPM]); vigorous PA, VPA = 5725-∞CPM; moderate-to-vigorous PA, MVPA = 1952-∞CPM; daily steps), through: Spearman's correlations (ρ) for continuous data; %agreement, Kappa, sensitivity and specificity, positive and negative predictive values (PPV, NPV) for categorical data. RESULTS: The BPAAT identified 73.6% patients as "insufficiently active" and 26.4% as "sufficiently active". The BPAAT was weakly to moderately correlated with accelerometry (0.394 ≤ ρ ≤ 0.435, P < 0.05), except for VPA (P = 0.440). This was also observed in age (<65/≥65yrs), COPD grades (GOLD 1-2/3-4) and in male patients (0.363 ≤ ρ ≤ 0.518, P < 0.05 except for VPA). No significant correlations were found in female patients (P > 0.05). Agreement was fair to moderate (0.36 ≤ κ ≤ 0.43; 73.6% ≤ %agreement ≤ 74.5%; 0.50 ≤ sensitivity ≤ 0.52; 0.84 ≤ specificity ≤ 0.91, 0.55 ≤ PPV ≤ 0.79, 0.72 ≤ NPV ≤ 0.82). CONCLUSION: The BPAAT may be useful to screen patients' PA, independently of age and COPD grade, and identify male patients who are insufficiently active. Care should be taken when using this tool to assess vigorous PA or female patients.

What Motivates Patients with COPD to Be Physically Active? A Cross-Sectional Study.

Motivation can be broadly defined as what moves people to act. Low motivation is a frequently reported factor for the reduced physical activity (PA) levels observed in patients with chronic obstructive pulmonary disease (COPD). This study assessed patients' motives to be physically active, according to three pulmonary rehabilitation (PR) participation groups (Never PR, Previous PR and Current PR) and explored whether these motives were related to the PA levels and clinical characteristics. The motives to be physically active were assessed with the Exercise Motivation Inventory-2 (EMI-2, 14 motivational factors, five dimensions) and PA with accelerometry (PA groups: <5000 steps/day vs. ≥5000 steps/day). The clinical variables included symptoms, impact of the disease, exercise capacity and comorbidities. Ninety-two patients (67.4 ± 8.1 years, 82.6% male, forced expiratory volume in 1s (FEV1) 48.3 ± 18.9% predicted; 30.4% Never PR, 51% Previous PR and 18.5% Current PR) participated. The motivational dimensions related to health/fitness presented the highest scores (3.8 ± 1.1; 3.4 ± 1.3). The motives to be active were not significantly different between PA groups (p > 0.05) but having less symptoms and ≥two comorbidities were associated with higher scores in psychological/health and body-related motives, respectively (p < 0.05). The findings may encourage health professionals to actively explore with patients their motives to be physically active to individualise PA promotion.

Update of the Mexican College of Rheumatology Guidelines for the Pharmacological Treatment of Rheumatoid Arthritis, 2018. / Actualización de las guías del tratamiento farmacológico de la artritis reumatoide del Colegio Mexicano de Reumatología 2018.

Therapeutic advances in rheumatoid arthritis require periodic review of treatment guidelines. OBJECTIVE: To update the Mexican College of Rheumatology guidelines on the pharmacological treatment of rheumatoid arthritis. METHOD: Board certified rheumatologists from different health institutions and regions of the country participated. Work teams were formed that reviewed the previous guidelines, elaborated new questions, reviewed the literature, and scored the evidence that was presented and discussed in plenary session. The conclusions were presented to infectologists, gynaecologists and patients. Recommendations were based on levels of evidence according to GRADE methodology. RESULTS: Updated recommendations on the use of available medications for rheumatoid arthritis treatment in Mexico up to 2017 are presented. The importance of adequate and sustained control of the disease is emphasized and relevant safety aspects are described. Bioethical conflicts are included, and government action is invited to strengthen correct treatment of the disease. CONCLUSIONS: The updated recommendations of the Mexican College of Rheumatology on the pharmacological treatment of rheumatoid arthritis incorporate the best available information to be used in the Mexican health care system.

Minimal Clinically Important Differences for Patient-Reported Outcome Measures of Fatigue in Patients With COPD Following Pulmonary Rehabilitation.

BACKGROUND: Fatigue is a burdensome and prevailing symptom in patients with COPD. Pulmonary rehabilitation (PR) improves fatigue; however, interpreting when such improvement is clinically relevant is challenging. Minimal clinically important differences (MCIDs) for instruments assessing fatigue are warranted to better tailor PR and guide clinical decisions. RESEARCH QUESTION: This study estimated MCIDs for the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale (FACIT-FS), the modified FACIT-FS, and the Checklist Individual Strength-Fatigue Subscale in patients with COPD following PR. STUDY DESIGN AND METHODS: Data from patients with COPD who completed a 12-week community-based PR program were used to compute the MCIDs. The pooled MCID was estimated by calculating the arithmetic weighted mean, resulting from the combination of anchor-based (weight, two-thirds) and distribution-based (weight, one-third) methods. Anchors were patients' and physiotherapists' Global Rating of Change Scale, COPD Assessment Test, St. George's Respiratory Questionnaire (SGRQ), and exacerbations. To estimate MCIDs, we used mean change, receiver-operating characteristic curves, and linear regression analysis for anchor-based approaches, and 0.5 × SD, SE of measurement, 1.96 × SE of measurement, and minimal detectable change for distribution-based approaches. RESULTS: Fifty-three patients with COPD (79% male, 68.4 ± 7.6 years of age, and FEV1 48.7 ± 17.4% predicted) were included in the analysis. Exacerbations and the SGRQ-impact and the SGRQ-total scores fulfilled the requirements to be used as anchors. Pooled MCIDs were 4.7 for FACIT-FS, 3.8 for the modified FACIT-FS, and 9.3 for the Checklist Individual Strength-Fatigue Subscale. INTRPRETATION: The MCIDs proposed in this study can be used by different stakeholders to interpret PR effectiveness. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03799666; URL: www.clinicaltrials.gov.

Minimal Clinically Important Differences for Patient-Reported Outcome Measures of Cough and Sputum in Patients with COPD.

Background: Cough and sputum are highly prevalent in patients with chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) has shown to be effective in managing these symptoms. However, the interpretation of the magnitude of PR effects is hindered by the lack of minimal clinically important differences (MCIDs). Purpose: This study established MCIDs for the Leicester cough questionnaire (LCQ) and the cough and sputum assessment questionnaire (CASA-Q), in patients with COPD after PR. Patients and Methods: An observational prospective study was conducted in patients with COPD who participated in a 12-weeks community-based PR program. Anchor- (mean change, receiver operating characteristic curves and linear regression analysis) and distribution-based methods [0.5*standard deviation; standard error of measurement (SEM); 1.96*SEM; minimal detectable change and effect size] were used to compute the MCIDs. The anchors used were: i) patients and physiotherapists global rating of change scale, ii) COPD assessment test, iii) St. George's respiratory questionnaire and iv) occurrence of an exacerbation during PR. Pooled MCIDs were computed using the arithmetic weighted mean (2/3 for anchor- and 1/3 for distribution-based methods). Results: Forty-nine patients with COPD (81.6% male, 69.8±7.4years, FEV150.4±19.4%predicted) were used in the analysis. The pooled MCIDs were 1.3 for LCQ and for CASA-Q domains were: 10.6 - cough symptoms; 10.1 - cough impact; 9.5 - sputum symptoms and 7.8 - sputum impact. Conclusion: The MCIDs found in this study are potential estimates to interpret PR effects on cough and sputum, and may contribute to guide interventions.

Ambulatory Versus Laboratory Polysomnography in Obstructive Sleep Apnea: Comparative Assessment of Quality, Clinical Efficacy, Treatment Compliance, and Quality of Life.

STUDY OBJECTIVES: This study has as its primary objective to evaluate the quality and effectiveness of type II ambulatory polysomnography (Amb-PSG) versus type I attended laboratory polysomnography (Lab-PSG) in diagnosing obstructive sleep apnea (OSA). Its secondary objective is to evaluate the clinical efficacy, quality of life (QoL), and treatment adherence after diagnosis. METHODS: An observational study of patients with OSA (n = 225) in whom diagnosis was made via Amb-PSG (n = 114) or Lab-PSG (n = 111). Patients' clinical data were retrospectively assessed (including general demographic and clinical data, Epworth Sleepiness Scale, blood pressure, indices from polysomnography, and treatment adherence. Cross-sectional assessment (patient questionnaire) was used to evaluate clinical efficacy indicators, comorbidities, current treatment, and QoL. RESULTS: Polysomnography indices were comparable between Amb-PSG and Lab-PSG (apnea-hypopnea index: 38.9 ± 22.5 versus 35.8 ± 23.1 events/h; P > .05), except for an elevation of total sleep time (510 ± 54.7 versus 476.3 ± 79.4 minutes; P < .01) and loss of oximetry signal (9.8% versus 0.0%; P < .05). Based on polysomnography parameters, OSA was severe in 119 patients (52.9%), moderate in 88 (39.1%), and mild in 18 (8.0%). Diagnostic effect of Amb-PSG in clinical (body mass index, blood pressure, Epworth Sleepiness Scale) and treatment follow-up (CPAP adherence and QoL) indicators was comparable to that of Lab-PSG. CONCLUSIONS: Amb-PSG showed an OSA diagnostic capacity comparable to Lab-PSG. Secondary analyses (diagnostic quality, clinical efficacy, treatment compliance, QoL) underline the value of Amb-PSG as an emerging alternative to improve accessibility to care.

Educational interventions to improve inhaler techniques and their impact on asthma and COPD control: a pilot effectiveness-implementation trial.

To assess the impact that educational interventions to improve inhaler techniques have on the clinical and functional control of asthma and COPD, we evaluated 44 participants before and after such an intervention. There was a significant decrease in the number of errors, and 20 patients (46%) significantly improved their technique regarding prior exhalation and breath hold. In the asthma group, there were significant improvements in the mean FEV1, FVC, and PEF (of 6.4%, 8.6%, and 8.3% respectively). Those improvements were accompanied by improvements in Control of Allergic Rhinitis and Asthma Test scores but not in Asthma Control Test scores. In the COPD group, there were no significant variations. In asthma patients, educational interventions appear to improve inhaler technique, clinical control, and functional control. RESUMO Para avaliar o impacto do ensino da técnica inalatória no controle clínico e funcional de pacientes com asma ou DPOC, incluíram-se 44 participantes antes e após essa intervenção. Houve uma diminuição significativa no número de erros cometidos, sendo que 20 pacientes (46%) melhoraram significativamente sua técnica na expiração prévia e apneia final. No grupo asma, houve significativa melhora nas médias de FEV1 (6,4%), CVF (8,6%) e PFE (8,3%), e essa melhora correlacionou-se com os resultados no Control of Allergic Rhinitis and Asthma Test, mas não com os do Asthma Control Test. No grupo DPOC, não houve variações significativas. O ensino da técnica inalatória parece melhorar seu desempenho e os controles clínico e funcional em pacientes com asma.

Assessment of Inhalation Technique in Clinical and Functional Control of Asthma and Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Chronic obstructive pulmonary disease and asthma affect almost 300 million individuals. Inhaled therapy is often associated with technical errors reducing efficacy and compliance. OBJECTIVE: To evaluate the inhalation technique and its relation with clinical and functional control in asthma and chronic obstructive pulmonary disease. MATERIAL AND METHODS: Analytical cross-sectional study including patients with asthma and chronic obstructive pulmonary disease treated with any type of inhaler device. Demographic data and inquiry about previous teaching of inhalation technique were collected in all participants. Inhalation technique was evaluated in: Step 1 - device activation; Step 2 - previous expiration; Step 3 - inspiration; Step 4 - end inspiratory pause. Clinical control was assessed from the questionnaires Asthma Control Test, Control of Allergic Rhinitis and Asthma Test, modified Medical Research Council and Chronic Obstructive Pulmonary Disease Assessment Test. Spirometric evaluation was performed in all participants. RESULTS: From a total of 62 subjects, 74.19% made at least one error, mainly during step 2 (53.2%). Previous education on inhalation technique was associated with lower number of errors (p = 0.014). There was no association between number of errors and age (p = 0.321), years of diagnosis (p = 0.119) or spirometric evaluation (p > 0.05). In asthma an association was found between number of errors and Asthma Control Test (p = 0.032) and Control of Allergic Rhinitis and Asthma Test (p = 0.008). DISCUSSION AND CONCLUSION: Teaching inhalation technique has a positive impact on its future performance. Most patients make mistakes, affecting clinical control in asthma, although in chronic obstructive pulmonary disease no relation was found. This is an ongoing work that aims to reevaluate inhalation technique after patients' education and its further impact.

Introdução: A doença pulmonar obstrutiva crónica e a asma afectam quase 300 milhões de indivíduos em todo o mundo. A terapêutica inalatória associa-se frequentemente a erros na técnica realizada reduzindo a eficácia e adesão.Objectivo: Avaliar a técnica inalatória e sua relação com o controlo clínico e funcional em asma e doença pulmonar obstrutiva crónica. Material e Métodos: Estudo transversal analítico incluindo doentes com asma e doença pulmonar obstrutiva crónica medicados com dispositivos inalatórios. Recolheram-se dados demográficos e existência de ensino prévio da técnica. Avaliou-se a técnica inalatória em: Passo 1 - expiração prévia; Passo 2 - activação do dispositivo; Passo 3 - inspiração; Passo 4 - apneia final. O controlo clínico avaliou-se com os questionários Asthma Control Test, Control of Allergic Rhinitis and Asthma Test, modified Medical Research Council e Chronic Obstructive Pulmonary Disease Assessment Test. Todos os participantes realizaram avaliação espirométrica. Resultados: Obtiveram-se 62 participantes, dos quais 74,19% cometeram pelo menos um erro na inalação, principalmente na expiração prévia (53,2%). A existência prévia de ensino da técnica associou-se a menor n'º de erros (p = 0,014). Não houve associação entre n'º de erros e idade (p = 0,321), n'º de anos de diagnóstico (p = 0,119) ou avaliação espirométrica (p > 0,05). Na asma encontrou-se associação entre menor número de erros e Asthma Control Test (p = 0,032) e Control of Allergic Rhinitis and Asthma Test (p = 0,008). Discussão e Conclusão: O ensino da técnica inalatória melhora o seu desempenho futuro. A maioria dos doentes comete erros afectando o controlo clínico na asma, apesar de na doença pulmonar obstrutiva crónica não se verificar nenhuma associação. Este trabalho encontra-se a decorrer procurando reavaliar os doentes após o ensino da técnica e verificar o seu impacto subsequente.

Educational interventions to improve inhaler techniques and their impact on asthma and COPD control: a pilot effectiveness-implementation trial / Educação para a melhora da técnica inalatória e seu impacto no controle da asma e DPOC: um estudo piloto de efetividade-intervenção

ABSTRACT To assess the impact that educational interventions to improve inhaler techniques have on the clinical and functional control of asthma and COPD, we evaluated 44 participants before and after such an intervention. There was a significant decrease in the number of errors, and 20 patients (46%) significantly improved their technique regarding prior exhalation and breath hold. In the asthma group, there were significant improvements in the mean FEV1, FVC, and PEF (of 6.4%, 8.6%, and 8.3% respectively). Those improvements were accompanied by improvements in Control of Allergic Rhinitis and Asthma Test scores but not in Asthma Control Test scores. In the COPD group, there were no significant variations. In asthma patients, educational interventions appear to improve inhaler technique, clinical control, and functional control.

RESUMO Para avaliar o impacto do ensino da técnica inalatória no controle clínico e funcional de pacientes com asma ou DPOC, incluíram-se 44 participantes antes e após essa intervenção. Houve uma diminuição significativa no número de erros cometidos, sendo que 20 pacientes (46%) melhoraram significativamente sua técnica na expiração prévia e apneia final. No grupo asma, houve significativa melhora nas médias de FEV1 (6,4%), CVF (8,6%) e PFE (8,3%), e essa melhora correlacionou-se com os resultados no Control of Allergic Rhinitis and Asthma Test, mas não com os do Asthma Control Test. No grupo DPOC, não houve variações significativas. O ensino da técnica inalatória parece melhorar seu desempenho e os controles clínico e funcional em pacientes com asma.

Treating severe systemic lupus erythematosus with rituximab. An open study.

Systemic lupus erythematosus (SLE) is an autoimmune disease that may be associated to high morbidity and mortality. Disease course is variable and unpredictable and although the prognosis and survival of these patients has dramatically improved, treatment of severe multiorganic organic affection in this condition remains a therapeutic challenge. Since B lymphocytes have an important role in the pathogenesis of SLE, it is expected that the targeting of these cells exerts a significant therapeutic effect in SLE patients with severe multiorganic manifestations. In an open clinical trial, we have explored the therapeutic potential of Rituximab (an anti-CD20 monoclonal antibody) administration in SLE patients with severe nephritis (n=22) or neuropsychiatric manifestations (n=6) or massive pulmonary hemorrhage (n=3). In most cases, we observed significant improvement in both clinical and laboratory parameters, with good tolerance and few side effects. Thus, patients with severe lupus nephritis showed improvement in disease activity (MEX-SLEDAI index) with a significant reduction (p<0.05), as well as proteinuria in most of them (from 3.710g/L to 1.786g/L, p<0.05); patients with serious neurologic involvement had complete remission of their manifestations; but those with pulmonary massive hemorrhage did not have any response. Rituximab could have an important therapeutic potential in severe SLE, and that it is necessary to carry out a controlled blinded clinical trial to further support this point.

Temperatura no desenvolvimento e na reprodução de cochonilhas criadas sobre abóboras / Temperature in the development and reproduction of scales reared on squash

O desenvolvimento de insetos é dependente da temperatura. Nesta pesquisa, foi verificada a influência da temperatura no desenvolvimento e na reprodução de Chrysomphalus aonidum (L.) em câmaras climatizadas com UR do ar 70±10 por cento, fotofase de 12h e temperaturas constantes de 17, 19, 21, 23, 25 e 27 ± 1°C, tendo como substrato abóboras "cabotiá" (Curcubita maxima x Curcubita moschata var. Tetsukabuto). Foi observada a influência da temperatura nos parâmetros biológicos da cochonilha, sendo que temperaturas entre 23 e 27°C foram as mais adequadas ao inseto, propiciando menor duração do período ninfal e maior produção diária de ninfas por fêmea. Temperaturas entre 17 e 19°C provocam maior duração na fase ninfal, maior longevidade das fêmeas e menor produção diária de ninfas por fêmea.

The development of the insects is dependent on the temperature. In this research, it was verified the influence of the temperature in the development and reproduction of the Chrysomphalus aonidum under climate controlled conditions (RH 70±10 percent, photophase of 12h), and seven constant temperatures of 17, 19, 21, 23, 25, and 27 ± 1°C); on "cabotiá" squash (Curcubita maxima x Curcubita moschata var. Tetsukabuto) substrate. The temperature had influence in the biological parameters of the scale. The temperatures between 23 and 27°C were the most adequate to the scale, causing smaller duration of the nymphal period, and higher daily production of nymphs per female. At the temperatures between 17 and 19°C, the scale presented higher duration in the nymphal phase, and longevity of the females and smaller daily production of nymphs per female.