Amalia Moreno

Omalizumab in the management of oral corticosteroid-dependent IGE-mediated asthma patients

Abstract Background: Several studies have demonstrated the beneficial effects of omalizumab in asthma patients. Here we describe the drug’s tolerance and oral corticosteroid sparing capacity in a long-term observational study. Methods: Thirty-two patients aged ≥18 years with obstructive airway disease and FEV1 reversibility ≥12% and 200 mL, with an oral steroid requirement ≥7.5 mg per day of prednisolone during a period of ≥1 year, a positive prick test or in vitro reactivity (RAST) to at least one perennial aeroallergen and a baseline immunoglobulin E level ranking between 30–700 IU/mL were prospectively followed for 17.2 ± 8.5 months. Patients were visited once or twice a month, depending on their schedule for omalizumab administration. Intervention: blood analysis every six months; spirometry and nitric oxide measurement at every visit. Results: One patient who dropped out early was excluded. Follow-up period: the treatment benefited 83.9% (26/31) of the cohort; oral corticosteroids were reduced from 7.19 ± 11.1 to 3.29 ± 11.03 mg (p < 0.002) and withdrawn in 74.2% of patients. FEV1 (percent predicted) was 64.4 ± 22.7 at the beginning and 62.9 ± 24.3 at the end. IgE at entry was 322.2 ± 334.2 IU/mL and increased 2.34-fold. Respiratory function and NO did not present statistically significant changes. We identified three groups of patients: the first (n = 17) receiving oral steroid at entry in whom the accumulated dose of oral steroids progressively decreased; another (n = 10) including patients who had quit oral steroids before starting omalizumab although they had not been instructed to do so and whose oral steroid dose at the end of follow-up was zero; and a third group (n = 4) that did not benefit from omalizumab treatment. The only relevant side effect was a flu-like syndrome which required discontinuation of treatment in one patient. Conclusion: In our series, a substantial, safe decrease in oral corticosteroid requirements was observed due, at least to some extent, to omalizumab therapy. Oral corticosteroids were withdrawn in three-quarters of the patients. We were unable to identify a factor able to predict which patients would benefit most from omalizumab treatment.

Twelve years’ experience with methotrexate for GINA treatment step 5 asthma patients

ABSTRACT Background: Certain studies have shown the beneficial effects of methotrexate (MTX) in asthma patients. Here we describe the drugs tolerance and oral corticosteroid sparing capacity in a long-term observational study. Methods: Forty-four patients with steroid-dependent asthma treated with 10 mg per week of oral MTX were prospectively followed for 91.3 ± 39.5 months. Intervention: blood analysis each 3 months; spirometry monthly during the first 3 months and then every 3–6 months; liver ultrasound when an accumulated dose of 1500 mg was reached or whenever hepatic function was altered. Results: Two patients who dropped out early were excluded. Mean accumulated dose of MTX was 3.499 ± 2.207 mg. Corticosteroid use was reduced from 15.1 ± 8.2 to 2.64 ± 5.35 mg (p < 0.008) and was withdrawn in 25 patients. In the remaining 17 patients, the dose was reduced from 17.1 ± 9.1 mg to 6.5 ± 6.8 mg. FEV1 (% predicted) was 66.2 ± 19.7 at the beginning and 65.7 ± 19.1 at the end. Haematology was normal and only a mild increase in hepatic enzymes was observed in four patients, which normalized after treatment discontinuation. Hair loss was observed in one case. Conclusions: In our series, a substantial, safe decrease in oral corticosteroid requirements was observed, probably due, to some extent, to MTX therapy. Oral corticosteroids were withdrawn completely in 59% of patients. Liver function was impaired in some patients; however, it recovered after MTX withdrawal and MTX could be safely reintroduced. The association of oral corticosteroids and MTX did not increase the number of side-effects and immunity was not affected. We were unable to identify a factor that could predict which patients would benefit most from MTX treatment. Some limitations of the study include the lack of control of asthma exacerbations and the lack of booster courses of corticosteroids.

Causas de muerte en pacientes con EPOC grave. Factores pronósticos

OBJECTIVE The objective of this study was to assess the causes of death and risk factors for mortality in a cohort of patients with severe chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS We studied 203 patients with severe COPD (forced expiratory volume in 1 second [FEV(1)] <50%), who were attended in our respiratory department day hospital (2001-2006). Clinical variables were recorded on inclusion, and clinical course and causes of death were retrospectively reviewed. RESULTS The mean (SD) age of patients was 69 (8) years and the mean FEV(1) was 30.8% (8.2%). One-hundred and nine patients died (53.7%); death was attributed to respiratory causes in 72 (80.9%), with COPD exacerbation being the most frequent specific cause within this category (48.3%). During follow-up, 18.7% required admission to the intensive care unit (ICU). Survival at 1, 3, and 5 years was 80%, 53%, and 26%, respectively. The multivariate analysis showed that mortality was associated with age, stage IV classification according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), cor pulmonale, and hospital admission during the year prior to inclusion. Need for admission to the ICU during follow-up was a factor independently associated with higher mortality. CONCLUSIONS Mortality in patients with severe COPD was high and exacerbation of the disease was one of the most frequent causes of death. Age, GOLD stage, cor pulmonale, prior admission to hospital, and need for admission to the ICU during follow-up were independent predictors of mortality.

Causes of Death and Risk Factors for Mortality in Patients With Severe Chronic Obstructive Pulmonary Disease

Abstract Objective The objective of this study was to assess the causes of death and risk factors for mortality in a cohort of patients with severe chronic obstructive pulmonary disease (COPD). Patients and methods We studied 203 patients with severe COPD (forced expiratory volume in 1 second [FEV1] Results The mean (SD) age of patients was 69 (8) years and the mean FEV1 was 30.8% (8.2%). One-hundred and nine patients died (53.7%); death was attributed to respiratory causes in 72 (80.9%), with COPD exacerbation being the most frequent specific cause within this category (48.3%). During follow-up, 18.7% required admission to the intensive care unit (ICU). Survival at 1, 3, and 5 years was 80%, 53%, and 26%, respectively. The multivariate analysis showed that mortality was associated with age, stage IV classification according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), cor pulmonale, and hospital admission during the year prior to inclusion. Need for admission to the ICU during follow-up was a factor independently associated with higher mortality. Conclusions Mortality in patients with severe COPD was high and exacerbation of the disease was one of the most frequent causes of death. Age, GOLD stage, cor pulmonale, prior admission to hospital, and need for admission to the ICU during follow-up were independent predictors of mortality.

Immunocytochemical Study of the Ultimobranchial Tubule in Wistar Rats

A systematic immunohistochemical study of the ultimobranchial tubule (UBT) has been carried out in 45 Wistar rats of different ages (0, 5, 10, 15, 20, 25, 30, 60 and 120 days). The existence of calcitonin immunoreactive cells in the UBT wall has been demonstrated in a 5‐days old rat. In addition, immunohistochemical studies for thyroglobulin revealed positive staining in follicular cells connected to the UBT and, occasionally, in isolated cells lying within solid clusters from the UBT. These last results together with the continued and repeated existence of numerous mitosis and PAS (+) microfollicles, apparently rising from the UBT, support the hypothesis that the ultimobranchial body (UBB) may contribute partially to the formation of a part of the follicular component.

Evidence of the Occurrence of Calcitonin Cells in the Ultimobranchial Follicle of the Rat Postnatal Thyroid

A study on thyroid glands of Wistar rats of ages ranging from 1 to 120 days was carried out. The glands were serially sectioned and stained for calcitonin using the peroxidase antiperoxidase method. All the thyroids contained ultimobranchial follicles (UBF) located partially embedded among the usual follicles but in a 5-day-old rat this structure showed an unusual position in the interstitium of connective tissue between the cartilage of the trachea and the thyroid gland. We have observed in the wall of that UBF the presence not only of resting C cells but also mitotic figures of C cells. Furthermore, on the opposite side of the same UBF an active area of formation of thyroid follicles was found. These observations provided the first evidence of the contribution of the UBF in the formation of C cells during the postnatal life of the rat. Furthermore, it is suggested that some C cells may share a common origin with ultimobranchially derived follicular cells.

Changes and Clinical Consequences of Smoking Cessation in Patients With COPD: A Prospective Analysis From the CHAIN Cohort

Background Despite the existing evidence‐based smoking cessation interventions, chances of achieving that goal in real life are still low among patients with COPD. We sought to evaluate the clinical consequences of changes in smoking habits in a large cohort of patients with COPD. Methods CHAIN (COPD History Assessment in Spain) is a Spanish multicenter study carried out at pulmonary clinics including active and former smokers with COPD. Smoking status was certified by clinical history and co‐oximetry. Clinical presentation and disease impact were recorded via validated questionnaires, including the London Chest Activity of Daily Living (LCADL) and the Hospital Anxiety and Depression Scale (HADS). No specific smoking cessation intervention was carried out. Factors associated with and clinical consequences of smoking cessation were analyzed by multivariate regression and decision tree analyses. Results One thousand and eighty‐one patients with COPD were included (male, 80.8%; age, 65.2 [SD 8.9] years; FEV1, 60.2 [20.5]%). During the 2‐year follow‐up time (visit 2, 906 patients; visit 3, 791 patients), the majority of patients maintained the same smoking habit. Decision tree analysis detected chronic expectoration as the most relevant variable to identify persistent quitters in the future, followed by an LCADL questionnaire (cutoff 9 points). Total anxiety HADS score was the most relevant clinical impact associated with giving up tobacco, followed by the LCADL questionnaire with a cutoff value of 10 points. Conclusions In this real‐life prospective COPD cohort with no specific antismoking intervention, the majority of patients did not change their smoking status. Our study also identifies baseline expectoration, anxiety, and dyspnea with daily activities as the major determinants of smoking status in COPD. Trial Registry ClinicalTrials.gov; No. NCT01122758; URL: www.clinicaltrials.gov.

Optimal Clinical Time for Reliable Measurement of Transcutaneous CO2 with Ear Probes: Counterbalancing Overshoot and the Vasodilatation Effect

OBJECTIVES: To determine the optimal clinical reading time for the transcutaneous measurement of oxygen saturation (SpO2) and transcutaneous CO2 (TcPCO2) in awake spontaneously breathing individuals, considering the overshoot phenomenon (transient overestimation of arterial PaCO2). EXPERIMENTAL SECTION: Observational study of 91 (75 men) individuals undergoing forced spirometry, measurement of SpO2 and TcPCO2 with the SenTec monitor every two minutes until minute 20 and arterial blood gas (ABG) analysis. Overshoot severity: (a) mild (0.1–1.9 mm Hg); (b) moderate (2–4.9 mm Hg); (c) severe: (>5 mm Hg). The mean difference was calculated for SpO2 and TcPCO2 and arterial values of PaCO2 and SpO2. The intraclass correlation coefficient (ICC) between monitor readings and blood values was calculated as a measure of agreement. RESULTS: The mean age was 63.1 ± 11.8 years. Spirometric values: FVC: 75.4 ± 6.2%; FEV1: 72.9 ± 23.9%; FEV1/FVC: 70 ± 15.5%. ABG: PaO2: 82.6 ± 13.2; PaCO2: 39.9.1 ± 4.8 mmHg; SaO2: 95.3 ± 4.4%. Overshoot analysis: overshoot was mild in 33 (36.3%) patients, moderate in 20 (22%) and severe in nine (10%); no overshoot was observed in 29 (31%) patients. The lowest mean differences between arterial blood gas and TcPCO2 was −0.57 mmHg at minute 10, although the highest ICC was obtained at minutes 12 and 14 (>0.8). The overshoot lost its influence after minute 12. For SpO2, measurements were reliable at minute 2. CONCLUSIONS: The optimal clinical reading measurement recommended for the ear lobe TcPCO2 measurement ranges between minute 12 and 14. The SpO2 measurement can be performed at minute 2.