Renato Vaccaro

Cromolyn versus nedocromil: Duration of action in exercise-induced asthma in children

Cromolyn sodium (10 mg), nedocromil sodium (4 mg), and placebo, all delivered by a metered dose inhaler, were compared in their efficacy and duration of action in preventing exercise-induced asthma in children. After a screening test was performed, 13 patients with asthma performed standard exercise tests 20 minutes and 140 minutes after drug inhalation in a randomized, double-blind, crossover study. Both drugs were significantly more protective than placebo after 20 minutes, but no significant difference was seen between cromolyn sodium and nedocromil sodium. No difference between active drugs and placebo was found 140 minutes after inhalation. At these clinically recommended doses both cromolyn sodium and nedocromil sodium provide equal protection against exercise-induced asthma, and the duration of action of both lasts for less than 2 hours.

Comparison of the protective effects of cromolyn sodium and nedocromil sodium in the treatment of exercise-induced asthma in children

Seventeen children with asthma were studied in a double-blind, crossover, placebo-controlled study designed to compare the efficacy of cromolyn sodium with that of nedocromil sodium in preventing exercise-induced asthma. All drugs were delivered through a metered-dose inhaler (cromolyn sodium, 10 mg; nedocromil sodium, 4 mg; placebo, two puffs). Nedocromil sodium and cromolyn sodium provided significant, comparable protection from exercise-induced asthma, and both drugs were better than placebo. We conclude that nedocromil sodium and cromolyn sodium administered by a pressurized aerosol provide equal protection against exercise-induced asthma in children.

Salmeterol in exercise-induced bronchoconstriction in asthmatic children: comparison of two doses

Since the optimal dose of salmeterol in asthmatic children has not yet been clearly defined, we compared the efficacy and duration of the protective effect of two doses of salmeterol (25 and 50 micrograms) against exercise-induced bronchoconstriction. Twelve children (aged 7-14 yrs) with asthma were studied in a double-blind, cross-over, placebo-controlled design. On three separate days, exercise tests were performed 1 h and 12 h after administration of the drug. Pulmonary function measurements were performed before drug inhalation, before every exercise test and 1, 5, 10, 15 and 30 min after the end of exercise. The response was expressed as maximal decrease in forced expiratory volume in one second (FEV1). Both doses of salmeterol provided significant bronchodilation for up to 12 h, with no difference between them. Maximal exercise-induced decrease in FEV1 (% fall) 1 h after pretreatment was (mean +/- SD) 35 +/- 16, 10 +/- 10 and 4 +/- 3% for placebo, 25 and 50 micrograms salmeterol, respectively. At 12 h after pretreatment these values were 31 +/- 14, 19 +/- 12 and 15 +/- 13%, respectively. Individual protection against exercise-induced bronchoconstriction at 1 and 12 h did not vary between the dosages (p < 0.05), even though the protection obtained by 25 micrograms at 12 h was no longer significant versus placebo. We conclude that 25 micrograms of inhaled salmeterol provides equally effective long-lasting bronchodilation and acute protection against exercise-induced bronchoconstriction as 50 micrograms, and may be a suitable dose for most asthmatic children.

Tuberculin skin test reactivity in Kawasaki disease.

A strongly positive tuberculin skin reaction (>1.5 cm2) was observed during the acute phase of the illness in 11 children with Kawasaki disease (KD), but not in control pediatric patients with other febrile infections (41 patients) or diseases similar to KD (9 patients). The cutaneous sensitvity to intermediate strength [5 tuberculin units (TU)] purified protein derivative (PPD) inoculation had completely disappeared by the second monthly checkup. Peripheral blood T lymphocytes from KD subjects proliferated vigorously and produced significant amounts of IL-2 in response to the stimulation elicited by 0.05 TU/mL of PPD. In contrast, the proliferative response of, and IL-2 release by, control T cells was within background values. Mounting laboratory evidence suggests that heat shock proteins (HSP) may be involved in the pathogenesis of KD. Our clinical and experimental data may, therefore, have been due to immunologic cross-reactivity between mycobacterial derived HSP65 and its human homologue HPS63 (self P1 antigen). Despite the low number of patients investigated, our findings suggest that the tuberculin skin test and its in vitro correlates (T cell mitogenesis and IL-2 production) could provide simple and reliable diagnostic tools for identifying atypical forms of KD, or vice versa, in subjects not vaccinated against tuberculosis.

Soluble CD30 Antigen in Human Colostrum

It is now well established that the CD30 glycoprotein is a surface antigen expressed by activated T cells producing T-helper (Th)-2-type lymphokines. Mounting laboratory evidence, however, suggests that CD30 expression is not confined to a functionally restricted subset of T cells, but also identifies activated cells with a Th-1 and Th-0 pattern of cytokine secretion. CD30-bearing T lymphocytes release a soluble form of the molecule (sCD30), which can be detected both in vitro and in vivo. In the present study, very high levels of sCD30 were found in colostrum from 20 puerperal women, but not in autologous and heterologous (nonpregnant women) blood samples. These data strongly support an involvement of CD30+ T cells in the immune processes which take place at the level of the mammary gland during pregnancy and lactation. Passively transferred immune components such as immunoglobulins, cytokines, macrophages, natural killer cells, granulocytes and memory/activated T cells, all of which may help the baby to fight off infections, have been revealed in human breast milk. However, how Th-2-type cytokine-secreting T cells or other T-cell types help to endow the congenitally immunocompromised newborn infant with extrinsic immunological support remains an open question.

γ T cells are decreased in the blood of children with Bordetella pertussis infection

The biological role of T cell receptor (TCR) γ bearing cells is not yet fully understood. We studied 12 children with Bordetella pertussis infection and 12 age‐ and sex‐matched healthy controls. Patients with whooping‐cough yielded significantly lower relative and absolute numbers of blood TCR‐γ+ cells than normal controls (both p < 0.001). It is suggested that the depletion of circulating γ T cells in patients with Bordetella pertussis infection might be the result of the dispatch of these cells to the site of inflammation, i.e. the bronchial mucosa. Interestingly, other human lung diseases, such as allergic bronchial asthma and sarcoidosis display similar pulmonary phenotypical features.

Memory T cells in human breast milk

Monoclonal antibodies (MoAbs) anti-CD45R (2H4) and anti-CDw29 (4B4) recognize two T-lymphocyte surface antigens. Within the CD4’ population, the antiCD45R MoAb appears to identify the suppressor-inducer subset, whereas the CDw29 antigen characterizes a reciprocal subpopulation of resting T cells with helper-inducer function. Although CD8’ lymphocytes can be phenotypically subdivided in the same way, their correlated functions are at present unknown. While it has generally been assumed that these subsets represent distinct lineages of T cells, recent data strongly suggest that they, instead, correspond to different maturational stages. According to this new interpretation, “naive” (unsensitized) T cells are located in the CD45R’ subset, whereas “memory” (antigen-primed) T lymphocytes are confined to the CDw29+ subpopulation (1). Since human colostrum and milk contain both CD4’ and CD8’ cells (2), we used the 2H4 and 4B4 MoAbs to ascertain whether there was preferential migration of “naive” or “memory” T cells to the mammary gland during lactation.

Peripheral blood γδ T cells in human listeriosis

A phenotypical analysis carried out by direct immunofluorescence and two‐colour cytofluorometry showed that the number of lymphocytes bearing the γδ T‐cell receptor heterodimer was increased in the blood of eight children with Listeria monocytogenes infection, mainly due to an expansion of cells identified by monoclonal antibodies which recognize Vγ2 gene products. These findings are further evidence that γδ T cells are in some way involved in the immune response directed against human intracellular pathogens.

CD26 and CD31 Surface Antigen Expression on Human Colostral T Cells

The expression levels of CD26 and CD31 surface antigens, two adhesion/activation molecules with helper and suppressor activities, respectively, were found to be significantly higher on human colostral T cells (CD3+) than in autologous peripheral blood samples. These findings provide further phenotypical evidence that immune system T lymphocytes are compartmentalized in the mammary gland late in pregnancy and during lactation. The question of whether these overexpanded T lymphocyte populations in breast milk modulate in situ, either by enhancing or suppressing, the cellular and/or humoral immune response of the suckling infant remains to be answered. Additional studies are, therefore, needed to explore this intriguing field concerning the immunology of the colostrum.

Acute infectious lymphocytosis: phenotype of the proliferating cell.

ABSTRACT. A case of acute infectious lymphocytosis in an otherwise healthy 2‐year‐old child is reported. Marker analysis of the expanded blood lymphocytes showed that they were predominantly T cells and that there was a considerable increase in the helper/inducer phenotype (OKT4+) population. However, the lymphocyte response to polyclonal T‐cell activators was low. This is the first report on T‐cell subset distribution in acute infectious lymphocytosis.