Beyond forced exhalation: impulse oscillometry as a promising tool for bronchial hyperresponsiveness evaluation.

Introduction: The multiple forced expiratory maneuvers that must be performed during methacholine test require a high degree of collaboration and can lead to fatigue. However, impulse oscillometry (IOS) is a noninvasive test, quick and easy to perform, that does not require effort-dependent maneuvers.Objectives: The primary endpoint was to evaluate the relationship between IOS and spirometry during the methacholine test. The secondary endpoint was to study the predictive value of baseline IOS in the development of bronchial hyperreactivity.Methods: Observational, prospective, cross-sectional study, with recruitment of consecutive patients from the pulmonology department with clinical suspicion of bronchial asthma with negative bronchodilator test and normal FeNO.Results: Twenty-five patients were included, with a mean age of 49 ± 18 years. Thirteen patients (52%) had a positive methacholine test. The correlation between IOS indices and FEV1 was significant (p < 0.05) in all cases. The indices with the highest predictive power were R5-20 and AX. The optimal cutoff points were an increase of greater than 32.96% in R5, greater than 120.83% for X5, an increase of 30.30 [kPa l-1s-1] in R5-20, and an increase of 1.01 [kPa l-1] for AX. Baseline oscillometry demonstrated a strong predictive value in the development of bronchial hyperreactivity, with a sensitivity of 61.5% and a specificity of 91.7%, using the cut-off point of 160.0% for R5.Conclusions: IOS may be a valuable alternative to forced spirometry in detecting bronchial hyperreactivity during the methacholine test, showing a good correlation between both tests.

Understanding Severe Asthma Through Small and Big Data in Spanish Hospitals: The PAGE Study.

BACKGROUND: Data on the prevalence of severe asthma (SA) are limited. Electronic health records (EHRs) offer a unique research opportunity to test machine learning (ML) tools in epidemiological studies. Our aim was to estimate the prevalence of SA among asthma patients seen in hospital asthma units, using both ML-based and traditional research methodologies. Our secondary objective was to describe patients with nonsevere asthma (NSA) and SA over a follow-up of 12 months. METHODS: PAGE is a multicenter, controlled, observational study conducted in 36 Spanish hospitals and split into 2 phases: a cross-sectional phase for estimation of the prevalence of SA and a prospective phase (3 visits in 12 months) for the follow-up and characterization of SA and NSA patients. A substudy with ML was performed in 6 hospitals. Our ML tool uses EHRead technology, which extracts clinical concepts from EHRs and standardizes them to SNOMED CT. RESULTS: The prevalence of SA among asthma patients in Spanish hospitals was 20.1%, compared with 9.7% using the ML tool. The proportion of SA phenotypes and the features of patients followed up were consistent with previous studies. The clinical predictions of patients' clinical course were unreliable, and ML found only 2 predictive models with discriminatory power to predict outcomes. CONCLUSION: This study is the first to estimate the prevalence of SA in hospitalized asthma patients and to predict patient outcomes using both standard and ML-based research techniques. Our findings offer relevant insights for further epidemiological and clinical research in SA.

PAGE Study: Summary of a Study Protocol to Estimate the Prevalence of Severe Asthma in Spain Using Big Data Methods.

BACKGROUND AND OBJECTIVES: Background: The proposal and the initiative for the Prevalence of Severe Asthma in Hospital Units in Spain (PAGE) study came about because of the widespread implementation of electronic medical records and the limited data available on the prevalence of severe asthma in hospitals in our setting. Objectives: The primary objective was to determine the prevalence of severe asthma in the outpatient clinics of allergy and pulmonology departments in Spain. The secondary objectives were to describe the most prevalent characteristics and phenotypes of severe asthma, to evaluate the selection criteria for receiving approved biological treatments for this disease, and to estimate consumption of resources. Furthermore, digital technology and new data collection sources made it possible to reuse information stored in electronic medical records (Big Data). The study was performed using one such tool, Savana. METHODS: The PAGE study was a multicenter, nonexperimental, observational, cross-sectional study in the first phase and a prospective study in the second phase. The study was controlled and population-based, with 2-stage selection of patients by random sampling. The research was carried out in 40 hospitals selected using convenience sampling in order to ensure geographical representativeness in Spain. RESULTS: This manuscript describes the study design and protocol. CONCLUSIONS: Our study design was sufficiently robust to avoid bias and to establish the prevalence of patients with severe asthma in Spanish hospitals. It was also the first to incorporate new tools that can help in routine clinical practice and research, such as big data analysis software, and to evaluate the reliability and efficiency of these tools.

[Ocular infiltration in the anterior chamber in a female infant with acute non-lymphoblastic leukemia]. / Infiltración de la cámara anterior ocular en una paciente con leucemia no linfoblástica aguda.

Unlike myeloid sarcoma, ocular involvement is unusual in acute non-lymphoblastic leukemia.A 9-month-old female infant with acute non-lymphoblastic leukemia M5 and evidence of active central nervous system (CNS) disease showed infiltration of the anterior chamber during therapy. At that time, the CNS disease was in completed remission. She was treated with topical corticosteroids, chemotherapy and bilateral ocular radiotherapy (total dose 1,000 cGy). The ocular manifestations responded well to treatment but hematologic response was poor. The patient died a few months later. Any ophthalmic manifestation in children with leukemia should be detected and treated early. Radiotherapy is warranted in infiltration of the anterior chamber of the eye. The presence of ocular, central CNS or bone marrow involvement indicates poor prognosis in acute childhood leukemia.

[Aggressive fibromatosis in childhood: retrospective analysis of four cases]. / Fibromatosis agresiva en la infancia: análisis retrospectivo de 4 casos.

OBJECTIVE: Aggressive fibromatosis is a rare illness in children. We analyzed the records of four patients, taken from a total of 505, all of which had different types of tumours, over a period of ten years. In the four cases, three were male and one female. Their ages ranged from 0-7 years old. We also did a review of this pathology. RESULTS: The illness may present itself a a painless mass found particularly in the pelvic area, knee, buttock and anterior mediastinum, respectively. Two of these cases presented lysis of osseous tissue shown in radiologic assays. The diagnosis was histological in every case. The only treatment was surgical in all of them. Two of the cases required only one intervention to achieve remission and up to now there has been no record of further illness. At the time of writing this paper the patients are alive after a follow-up period of thirty months. CONCLUSIONS: Up to now, no other alternative forms of treatment have been convincing. Adjuvant radiation and chemotherapy are probably beneficial, but the precise indication for its use is not well defined.

[The treatment results in children diagnosed with non-Hodgkin's lymphomas and acute B-cell lymphoblastic leukemias treated by the BFM protocols. The report of the POGM (Pediatric Oncology Group of Madrid)]. / Resultados del tratamiento de niños diagnosticados de linfomas no Hodgkin y leucemias linfoblásticas agudas de células B tratados con protocolos BFM. Informe del GOPM (Grupo de Oncología Pediátrica de Madrid).

OBJECTIVE: The purpose of this study was to reproduce the results obtained by the "BFM Group" in children with NHL and B-ALL treated with BFM 86 and 90 protocols. PATIENTS AND METHODS: From April 1987 until January 1997, we have treated a total of 82 children, 22 with non-B NHL, 49 B-NHL and 11 B-ALL. Forty-four of them were treated according to BFM 86 and 38 according to BFM 90 protocols. RESULTS: Ninety-four percent of the patients achieved complete remission (CR) and 15% of these relapsed, 12% of the cases of B NHL/ALL and 23% of the non-B NHL. The 5 year overall survival (Kaplan Meier) was 81% for the B NHL/ALL it was 83% and for non-B NHL 77%. The event-free survival was 75% for B-NHL, stages I and II it was 80% and stages II and IV 78%, for B-ALL 72% and for non-B NHL 68%. The median follow-up time was 50 months (12-106). CONCLUSIONS: Treatment of NHL and B-ALL with BFM protocols is an effective therapeutic choice, with reproduction of the results of the "BFM group" being feasible.

[Neuroblastoma in children under than 1 year of age]. / Neuroblastoma en niños menores de 1 año.

OBJECTIVE: Our objective was to carry out a prospective multicenter study of neuroblastoma patients diagnosed between 0 and 12 months of age. PATIENTS AND METHODS: Diagnostic procedures included histology, catecholamine excretion, bone marrow cytology and MIBG-scan. Staging was evaluated according to the INSS classification. After 1992, Simada criteria were used and also N-myc amplification, DNA index and P-glycoprotein determinations in tumoral tissue. The surgical technique employed and complications derived from it were also evaluated. The patients were treated according to stage with multicenter Spanish protocols N-I-87 and N-II-92. Overall survival and event free survival were calculated by actuarial methods. RESULTS: Between October 1987 and June 1992, a total of 140 infants less than one year of age were registered and diagnosed of neuroblastoma, representing 40% of all neuroblastoma cases. Median age was 0.3 years and 73% were less than 6 months of age at diagnosis. The most frequent stage was 1 (35%) followed by 4-S (20%). The frequency of unfavorable prognostic factors was the following: LDH (21%), NSE (14%), ferritin (18%), Shimada (7%), DNA (35%), NMA (3%), TrakA (23%), P-glycoprotein (19%). Surgery was performed in 133 children: total resection was reported in 94 and > 90% in another 22 cases. Complications attributed to surgery occurred in 12% of the cases. Chemotherapy was given in 73 cases and radiotherapy in 7. The five year total survival is 91% and the event free survival 88%. Survival by stages: Stage 1 = 91%, stage 2A = 88%, stage 2B = 100%, stage 3 = 84%, stage 4 = 56% and stage 4-S = 100%. CONCLUSIONS: 1) The majority of neuroblastoma cases in infants less than one year old are diagnosed before six months of age. 2) For this age group stages 1 and 4-S are the most frequently observed. 3) Unfavorable biological factors are less frequent than for children over one year of age and are associated with disseminated disease (advanced stage). 4) The outcome is excellent, except for stage 4 patients. The cases in stage 1 and 2 may be treated by surgery alone. Chemotherapy may be of benefit for stage 3 patients.

[The treatment results in children with malignant mesenchymal tumors according to the protocols of the International Society of Pediatric Oncology (SIOP)]. / Resultados del tratamiento de niños con tumores mesenquimales malignos según protocolos de la Sociedad Internacional de Oncología Pediátrica (SIOP).

OBJECTIVE: To evaluate the SIOP protocols in the treatment of mesenchymal tumors. PATIENTS AND METHODS: We present the results obtained in 28 children diagnosed at a single pediatric hematology-oncology unit of having malignant mesenchymal tumors. These diagnoses were made between April 1981 and June 1994 and the children were treated following the consecutive SIOP protocols which have the objective of curing the disease with minimal sequelae. The first four patients with rhabdomyosarcoma were treated with MMT-SIOP 75, the next 9 children, also diagnosed with rhabdomyosarcoma, were treated with MMT-SIOP 84. During the same period of time, there was a case of synovial sarcoma treated only with surgical excision. The last 14 patients were included in the current protocol, initiated in 1989. Eleven of these patients had rhabdomyosarcoma and 3 synovial sarcoma. RESULTS: Overall survival and event-free survival at 5 years were 58% and 36%, respectively. Toxicity never was an important factor, although it was increasingly frequent and severe as protocols evolved. CONCLUSIONS: We conclude that our results are similar to those obtained in patients treated with SIOP protocols.

[The results of treatment by the Madrid Pediatric Oncology Group according to the BFM protocols in non-Hodgkin's B-cell lymphoma and acute B-cell lymphoblastic leukemia in pediatric patients]. / Resultados del tratamiento según protocolos BFM del linfoma no Hodgkin B y de la leucemia linfoblástica aguda de células B en pacientes pediátricos por el GOPM.

The objective of this report is to present the results of the BFM group in the treatment of 41 children with non-Hodgkin's B cell lymphoma and acute B cell lymphoblastic leukemia according to the BFM 86 and 90 protocols. Forty-one children, between 2 and 16 years of age, were treated from November 1987 to October 1993. Of these, 25 were treated with the BFM 86 protocol (18 non-Hodgkin's B cell lymphomas and 7 acute B cell lymphoblastic leukemias) and the rest with the BFM 90 protocol (15 non-Hodgkin's B cell lymphomas and 1 acute B cell lymphoblastic leukemia). Complete remission was achieved in 97.5% of the patients. A relapse occurred in 12.5% of the cases. Currently, 80.4% remain in continuous complete remission and 17% have died. The 5 year actuarial survival rate of those treated with the BFM 86 and 90 protocols was 79% and 87%, respectively, and event free survival in the same period was 76% and 87%, respectively. There was no statistically significant difference in the results obtained with the two treatment protocols.

[Acute lymphoblastic leukemia: comparison of traditional treatment with intensive therapy methods]. / Leucemia linfoblástica aguda: comparación de los resultados del tratamiento clásico con terapias intensivas.

In this study we compare two different therapies for the treatment of non-B acute lymphoblastic leukemia (ALL). Forty-four children diagnosed as having non-B ALL were treated by one of two methods: 20 children were treated from 1981 to 1984 according to the PETHEMA 7/78 protocol and 24 children were treated from 1984 to 1987 following the BFM 83 protocol. These treatments differ in that BFM 83 includes a higher number of cytostatics, uses intravenous methotrexate at moderate doses as "reservoirs" treatment and a lower dose of holocranial radiotherapy. The BFM 83 treatment resulted in a significant improvement in survival (48% versus 92% p < 0.05), as well as in the absence of further events (45% versus 88%, p < 0.01).

[Treatment of infantile acute lymphoblastic leukemia with protocol ALL-BFM 83]. / Tratamiento de la leucemia aguda linfoblástica infantil con el protocolo ALL-BFM 83.

The outcome of 63 children with non-B acute lymphoblastic leukemia treated with ALL-BFM 83 protocol is analyzed. 95% achieved complete remission with the initial treatment. For the entire group the event free survival (EFS) was 66% (+/- 9%) at 48 months. These results were close to those obtained by the BFM group. Haematological toxicity was the main adverse effect, but there where no therapy related deaths. Persistence of more than 1,000 blast cells per microl in peripheral blood after 7th days of prednisone monotherapy, and spleen size greater than or equal to 5 cm under the costal margin, were identified as independent risk factors of high significance. The EFS in patients with poor clinical response to steroids (greater than or equal to 1,000 blast/microl at day 8) was 22% (+/- 18%), instead of 69% (+/- 12%) in those with adequate response.

[Review of 54 cases of idiopathic thrombocytopenic purpura. Evaluation of the response to treatment]. / Revisión de 54 casos de púrpura trombocitopénica idiopática. Valoración de la respuesta al tratamiento.

Fifty four cases of idiopathic thrombocytopenic purpura with an evolution longer than six months are reported. Total remission was achieved in 96.2% of patients, half of them without treatment. Etiologic agent, clinical features and response to different ways of treatment are analyzed.