Expiratory flow limitation and obstruction in the elderly.

Elderly people commonly suffer from dyspnoea, which may stem from expiratory flow limitation (EFL). The relationship between EFL, as assessed by the negative expiratory pressure method and spirometric indices, was investigated in an elderly French population. Subjects, aged 66-88 yrs, filled in socio-demographic and standardised questionnaires, which dealt with: medical history, smoking status and respiratory symptoms. EFL measurements and forced expiratory manoeuvres were performed. Validated measurements were obtained in 750 out of 1,318 subjects: 47% were EFL+ (EFL >0), with a higher prevalence in females than in males. EFL and forced expiratory volume in one second (FEV1) were correlated with age. A total of 116, from the 750 subjects, with no medical history and no symptoms, served as a healthy group. The prevalence of EFL+ subjects increased with the grade of dyspnoea and was highest in respiratory and cardiac patients when compared with the healthy subjects. EFL did not correlate with FEV1/forced vital capacity (FVC), the usual index of obstruction. Some elderly subjects (15%) with dyspnoea but with no medical history, mainly females with small FVC and normal FEV1/FVC, had a greater EFL than the healthy subjects. In elderly people, expiratory flow limitation measurements, along with the usual forced expiratory volume in one second/ forced vital capacity ratio, may be of value for the interpretation of dyspnoea.

IgE level and Phadiatop in an elderly population from the PAQUID cohort: relationship to respiratory symptoms and smoking.

BACKGROUND: In the last decades in industrialized countries, the increase of life expectancy has resulted in an increase in the population of the elderly. However, little is known about the prevalence of allergies in the elderly population. The aim of the study was to investigate the specific relationship of serum IgE and Phadiatop, with asthma, rhinitis, and smoking in a sample of an elderly population. METHODS: Subjects from the Paquid cohort living in Gironde Department (age 65 years and over) in France were followed up since 1988 (PAQUID cohort). RESULTS: Among the randomized sample of 352 subjects, there were 158 men (45%) and 194 women (55%). The lowest levels of IgE were in subjects with chronic sputum; and in normal subjects (47.1 +/- 56.4 vs 56.2 +/- 73.9, NS). Multiple linear regression was performed with log(10) IgE values as a dependent variable and age, Phadiatop test, smoking, and respiratory symptoms independently in men and in women. In men, a significant relationship was observed between IgE values and Phadiatop test (P < 0.001), asthma history (P = 0.002), and smoking (P = 0.019). CONCLUSIONS: Respiratory allergy is present in persons >65 years of age. There is an association between smoking and IgE level independent of allergic reactivity to common allergens in the elderly.

Factors influencing hematopoietic recovery after autologous blood stem cell transplantation in patients with acute myeloblastic leukemia and with non-myeloid malignancies.

Factors influencing hematopoietic recovery (HR) after autologous blood stem cell transplantation (ABSCT) were analyzed in 73 patients with various non-myeloid malignancies (NMM), and in 58 patients with acute myeloblastic leukemia (AML). Peripheral blood stem cells were collected following mobilization with chemotherapy, granulocyte colony-stimulating factor (G-CSF), or chemotherapy plus G-CSF. The conditioning regimen used consisted of either chemotherapy alone (112 cases) or chemotherapy plus total body irradiation (19 cases). The median number of colony-forming units granulocyte-macrophage (CFU-GM) was similar in both groups of patients, with the median number of CD34(+) cells infused being higher in the AML group (5.4 vs 4 x 10(6)/kg; P = 0.03). Median time neutrophils >0.5 x 10(9)/l was 13 days in both groups, and median time to a platelet count >20 x 10(9)/l was longer in AML patients (14 vs 12 days; P = 0.01). In multivariate analysis, the only factors affecting neutrophil recovery in the NMM group were the CD34+ cell number (continuous model) and the CFU-GM dose (categorized model) infused, whereas for platelet recovery, previous chemotherapy also remained significant. In the AML group, the only factors significantly affecting the speed of neutrophil recovery were dose of CD34+ cells administered and the patient's age. As for platelet recovery, only the progenitor dose administered remained significant. In the NMM group, the most discriminating cut-off values for a rapid neutrophil and platelet recovery were 1.5 x 10(6) and 2.5 x 10(6) CD34+ cells/kg, respectively, and for AML patients these figures were 1.5 x 10(6) and 4 x 10(6) CD34+ cells/kg, respectively. Our results confirm the slower HR after ABSCT in AML, and highlight the importance of progenitor cell dose in accelerating HR after ABSCT.

Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies.

The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults remains unclear. This study reports the results of UD-CBT in 22 adults with hematologic malignancies following conditioning with thiotepa, busulfan, cyclophosphamide, and antithymocyte globulin in 21, with thiotepa, fludarabine, and antithymocyte globulin in 1, and graft-versus-host disease (GVHD) prophylaxis with cyclosporine and prednisone. Median age was 29 years (range, 18-46 years), and median weight was 69.5 kg (range, 41-85 kg). HLA match was 6 of 6 in 1 case, 5 of 6 in 13 cases, and 4 of 6 in 8 cases. Median number of nucleated cells infused was 1.71 x 10(7)/kg (range, 1.01 x 10(7)/kg to 4.96 x 10(7)/kg). All 20 patients surviving more than 30 days had myeloid engraftment, and only 1, who received the lowest cell dose, developed secondary graft failure. Median time to reach an absolute neutrophil count of at least 0.5 x 10(9)/L was 22 days (range, 13-52 days). Median time to platelets numbered at least 20 x 10(9)/L was 69 days (range, 49-153 days). Seven patients (32%) developed acute GVHD above grade II, and 9 of 10 patients at risk developed chronic GVHD, which became extensive in 4 patients. Twelve patients remained alive and disease-free 3 to 45 months after transplantation. Disease-free survival (DFS) at 1 year was 53%. Age strongly influenced DFS (P =.01). For patients aged 30 years or younger, the DFS at 1 year was 73%. These preliminary results suggest that UD-CBT should be considered a reasonable alternative in young adults with hematologic malignancy and no appropriate bone marrow donor.

Dyspnea and 8-year mortality among elderly men and women: the PAQUID cohort study.

PAQUID is an epidemiological cohort which aims to study cerebral and functional factors of ageing. We have examined the relationship between dyspnea level at entrance into this cohort and mortality occurring during the subsequent 8 years. Dyspnea was evaluated by a questionnaire derived from a Fletcher's five-degree scale. Mortality was recorded during follow-up according to its date and cause. Of 2762 subjects (98.9%) initially giving their dyspnea level, 935 (33.5%) had died 8 years later including 444 (40%) men and 491 (29.4%) women. Mortality was closely related to dyspnea level (p < 0.0001) both in men and women, especially for grade 3 and over, even after adjusting on age, sex, smoking history and former occupation. These results show that dyspnea grade 3 or higher is an important predictive symptom of mortality, thus suggesting that this is a threshold defining the dyspneic subject.

Role of methylene blue-treated or fresh-frozen plasma in the response to plasma exchange in patients with thrombotic thrombocytopenic purpura.

Twenty patients with thrombotic thrombocytopenic purpura (TTP) underwent plasma exchange using either standard fresh-frozen plasma (Group A, n = 13) or methylene blue-treated plasma (Group B, n = 7). Both groups presented similar characteristics except that bilirubin values were higher in Group A (P < 0.05). The complete remission rate was higher in Group A than B (69% versus 57%). The mean number of procedures was higher in Group B (21 +/- 7 versus 11 +/- 3, P < 0.01) and the mean duration of hospitalization was also longer (37 +/- 12 d versus 22 +/- 11 d; P < 0.01). Our study shows that the use of methylene blue-treated fresh-frozen plasma to treat TTP is associated with a higher number of plasma exchanges and greater transfusion requirements without improving clinical results.

Development of non-ABO RBC alloantibodies in patients undergoing allogeneic HPC transplantation. Is ABO incompatibility a predisposing factor?

BACKGROUND: Data from the appearance of RBC antibodies other than ABO in patients undergoing HPC transplantation are limited. STUDY DESIGN AND METHODS: The incidence and specificity of non-ABO RBC alloantibodies are described in a series of 217 patients undergoing allogeneic HPC transplantation because of various hematologic malignancies. RESULTS: Eight patients (3.7%) developed 10 antibodies after transplant. None of these patients had previously been immunized. Seven patients had one RBC antibody and one patient had three RBC antibodies. Antibody specificity were anti-Jk(b) (2 patients), -Kell (2), -M (2), -Le(b) (1), and -D (1). Finally, two patients had a panagglutinin. The mean time between transplant and antibody detection was 23 days (range, 16-672). The source of the HPCs, the conditioning regimen administered, and the type of GVHD prophylaxis administered did not influence the rate of antibody formation. On multivariate analysis, ABO blood group incompatibility (p = 0.005) and patient's age (p = 0.02) were the only two variables significantly associated with the development of RBC alloantibodies. CONCLUSION: Patients undergoing allogeneic HPC transplantation are at risk of developing RBC-specific antibodies despite the immunosuppressive therapy administered. Antibody formation was more frequently observed in ABO-mismatched cases, which suggests a potential role of this incompatibility in facilitating antibody production.

Response to plasma exchange and steroids as combined therapy for patients with thrombotic thrombocytopenic purpura.

We describe our experience in the management of 11 consecutive patients with thrombotic thrombocytopenic purpura (TTP) treated with a combined therapy of plasma exchange (PE) and steroids. Nine patients (82%) achieved complete remission (CR) after a median of 6 rounds of PE (range 2-22). There were 3 early relapses managed in the same way as the initial episode. One patient relapsed 23 months after diagnosis achieving CR with standard therapy; another patient suffered several relapses, and splenectomy was performed after the last one. Three patients died, 2 of them with resistant disease 9 and 38 days after diagnosis, and the remaining one died due to AIDS-related complications while he was in CR. Eight patients are alive in CR with a median follow-up of 38 months (range 8-74). The combination of PE and steroids is a well-tolerated and effective treatment of TTP, but improvements in therapy are needed to manage refractory patients.

[Lymphocyte subsets in blood donors]. / Subpoblaciones linfocitarias en donantes de sangre.

OBJECTIVES: To establish the normal values among the different lymphocyte subsets in peripheral blood, measured by surface antigen expression, in healthy population. To observe if there are potential differences in respect of age, gender or sample origin. To compare the absolute lymphocyte number obtained with flow cytometry and with a cellular counter. MATERIAL AND METHODS: Longitudinal and prospective study performed with 100 samples of blood donors. Direct immunofluorescence with triple color staining was made on whole blood, red blood cells were then lysed and samples were analysed with a flow cytometer. The lymphocyte subsets studied were the T lymphocytes and their subsets (CD4 and CD8 lymphocytes), the B lymphocytes and Natural Killer cells population. The absolute lymphocyte count was performed with an automatic cellular counter. Donor data such as age, gender and origin were recorded and were statistically analysed. RESULTS: Normal ranges from the studied parameters are similar to other series. Comparison with gender, origin or age groups gave no significant difference, although there seems to be a tendency to decrease with the ageing of the population. Total absolute lymphocyte number did not differ between the results from the cellular counter or from the flow cytometer. CONCLUSIONS: We found no differences in the absolute lymphocyte number nor in the lymphocyte subsets studied (T lymphocytes, CD4 lymphocytes, CD8 lymphocytes, B lymphocytes and NK cells) with respect to gender, age or sample source. We have established reference ranges for our laboratory. We have not found significant differences in the absolute lymphocyte number measured with cell counter or with flow cytometer.

Severe hemolytic anemia due to multiple red cell alloantibodies after an ABO-incompatible allogeneic bone marrow transplant.

BACKGROUND: A patient who received an ABO-incompatible allogeneic bone marrow transplant experienced three episodes of immune hemolytic anemia due to multiple red cell (RBC) alloantibodies. CASE REPORT: A 41-year-old man with chronic myeloid leukemia received an ABO-incompatible bone marrow graft from his HLA-identical brother. Selective removal of RBCs from donor marrow before transfusion was performed by centrifugation using a continuous-flow blood cell separator. The patient was given group O Rh-positive RBCs and group A Rh-positive platelets. Prophylaxis for graft-versus-host disease consisted of cyclosporine and methotrexate. The patient experienced three hemolytic episodes, on Days 21, 35, and 160 which were due to different RBC alloantibodies (anti-K, anti-Jk(b), anti-M, IgG anti-A) produced by host lymphocytes surviving the conditioning regimen. RESULTS: The patient was group O, Jk(b-), and the marrow donor was group A, Jk(b+). After the first hemolytic episode (Day 21), immunohematologic studies showed group O RBCs and a positive direct antiglobulin test (IgG+, C3d+). Antibody screening test and eluate studies detected anti-M, anti-Jk(b), and anti-K. During the second hemolytic episode (Day 35), the patient's blood group showed a mixed population of group A and group O RBCs. The direct antiglobulin test was positive (IgG+, C3d+). Anti-M, anti-Jk(b), and IgG anti-A were detected in the serum. Eluates made from the recipient's RBCs showed the same specificity as serum antibodies. During the third hemolytic episode (Day 160), a mixture of group O and group A RBCs was still present, the direct antiglobulin test was positive (IgG+, C3d-), and anti-Jk(b) and IgG anti-A were observed in the serum and in an eluate made from the patient's RBCs. CONCLUSION: This is the first reported case of severe immune hemolytic anemia due to multiple RBC alloantibodies after an allogeneic bone marrow transplant. The time of appearance and the specificity of the antibodies strongly suggest that they were produced by residual recipient lymphoid cells.

[Immunohematologic study and transfusion approach to patients with public antibodies]. / Estudio inmunohematológico y actitud transfusional en pacientes con anticuerpos públicos.

OBJECTIVES: To analyze the different immunohematologic studies required to identify anti-red cell antibodies directed against high incidence antigens and comment the best tranfusion management. PATIENTS AND METHODS: Five patients with suspected anti-red cell alloantibodies directed against high frequency antigens are reported. After a positive antibody screening test (AST), an agglutination test with a commercial panel of 24 red cells was performed. Red cells were treated with proteolytic enzymes and AET to try to identify the circulating antibody. However, it was necessary to send the samples to reference laboratories for definitive identification. In order to evaluate the haemolytic potential of the antibody serum samples were treated with DTT and immunoglobulin subtype was studied with the capillary agglutination test. Finally, we analyze the half life of Cr51 labelled red cells. To obtain compatible blood for transfusion, autologous transfusion and cross-match with blood from direct relatives were performed. RESULTS: AST was positive in every case. A decrease in the agglutination test was observed after ficin treatment in two patients, and an increase in the remaining. The treatment of red cells with ZZAP and AET resulted in a decrease of agglutination in three cases and an increase in the remaining two. Specificity of the antibodies was as follows: anti-Cellano (two cases), anti-Ku (one case) and anti-Yta (two cases). Anti-Kell antibodies were IgG1 and anti-Cartwright antibodies were IgG4. One patient was transfused with autologous blood alone, another patient received compatible blood from direct relatives. A third patient was transfused both with autologous and allogeneic compatible blood. The fourth patient did not need red cell transfusion and, finally the last patient had to be transfused with incompatible blood but no postransfusion haemolysis was observed. CONCLUSIONS: In patients with anti-red cell antibodies against high-frequency antigens, red blood cells treatment with proteolytic enzymes (ZZAP, ficin) and AET are useful techniques to approach to their identification. Beside this, the study of type and subtype of Ig are necessary to know the haemolytic activity of the antibody. Regarding the transfusional management, autologous transfusion, crossmatch with blood from direct relatives and cryopreservation of compatible blood are the most adequate attitudes to cover future needs.

[Immunohematologic study in 112 patients with myelodysplastic syndromes: 10-year analysis]. / Estudio inmunohematológico en 112 pacientes con síndromes mielodisplásicos: análisis de 10 años.

PURPOSE: To describe the immunohematological response after multiple red blood cells transfusions in 112 patients with myelodysplastic syndromes (MDS). PATIENTS AND METHODS: From 1982 to 1992 every patient with MDS entered the study. Immunohematological studies consisted of an antibody screening test (AST) and a direct antiglobulin test (DAT) at diagnosis and after every four transfused units of red blood cell concentrates. RESULTS: Twenty-three out of 112 patients (20.5%) presented a positive AST and/or DAT during the study period. Eleven out of the 23 patients (9.8%) developed a positive DAT, six of them with red cell alloantibodies associated. In the remaining 12 patients (10.7%) the immune response observed was the development of red cell alloantibodies without a positive DAT. No patient presented with positive AST or DAT at diagnosis and no differences were observed in the pattern of immunohematological response and the FAB subtype. CONCLUSION: Patients with MDS have disordered immune systems with a high prevalence of autoantibodies against red cells. However, the incidence of red cell alloimmunization is similar to that observed in other multitransfused populations. Finally, despite the high immunization rate, the absence of any hemolytical reaction make the AST and DAT a safe and effective method of pretransfusion testing in this heavily transfused population.

[Transfusion policy toward a patient with an anti-Cartwright antibody (anti-Yta)]. / Actitud transfusional frente a un paciente con un anticuerpo anti-Cartwright (anti-Yta).

We have observed one patient with hepatic cirrhosis showing on her antibody screening an anti-Yta. We studied the 51 Cr-labelled erythrocyte survival using either Yt (a+) and autologous blood red cells. She was transfused two Yt (a+) red blood cell concentrates without any adverse reaction.