Short-term, high-dose, systemic steroids in children with asthma: the effect on the hypothalamic-pituitary-adrenal axis.

Children with chronic asthma frequently receive "bursts" (less than 7 days) of short-term, high-dose prednisone (1 to 2 mg/kg/day) for acute exacerbations of their disease. Certain of these patients may also require inhaled corticosteroids (IC) for control. The effect of these "bursts" on the hypothalamic-pituitary-adrenal axis (HPAA) is unclear. To test the integrity of the HPAA in such patients, we measured plasma cortisol (F) in response to serial administration of insulin-induced hypoglycemia (nadir = 34 +/- 1.2 mg/dl; mean +/- SE), followed by 250 micrograms/1.73 m2 of synthetic ACTH in the following children with asthma: group I, seven patients who received no more than one "burst" per year (0.71 +/- 0.2); group II, six individuals who received more than one "burst" per year (3.6 +/- 0.2) and no IC; and group III, 10 subjects who received more than one "burst" per year (4.7 +/- 0.3) plus IC. All patients received daily theophylline and beta-agonists; seven patients were taking sodium cromolyn. No patients received troleandomycin. Compared to group I (control subjects), 16% of group II had a subnormal response of F to hypoglycemia. In addition, a subnormal response of F to hypoglycemia or ACTH was documented in 20% and 10% of group III, respectively. All individuals with a subnormal response of F to either hypoglycemia or ACTH received four or more "bursts" per year. We conclude that as a group, children affected by asthma treated with "bursts" alone or "bursts" plus IC appear to have a normal HPAA.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypersensitivity reaction to a metabolite of cyclophosphamide.

Generalized urticaria and fever were noted in a patient with IgA (kappa) myeloma after intravenous cyclophosphamide. Intradermal skin testing revealed no reaction to cyclophosphamide and its analog, isophosphamide. However, phosphoramide mustard, a principle metabolite of cyclophosphamide, evoked an immediate wheal-and-flare response. Subsequent therapy with isophosphamide was well tolerated. These findings suggest that acute hypersensitivity reactions to cyclophosphamide are due to its metabolites and can be delineated with skin testing.

Suppressor T cells and soluble suppressor factors in allergy: effect of immunotherapy.

Suppressor-cell activity of Concanavalin-A-stimulated lymphocytes was studied in allergic patients by inhibition of one-way mixed lymphocyte culture reactions before and after allergy immunotherapy. This activity was compared with twelve healthy controls. In preliminary experiments, six out of eight allergic patients had no detectable T suppressor activity. In the second prospective group, eight out of eleven patients had much reduced suppressor-cell activity before immunotherapy, and seven out of eleven patients had much reduced activity after immunotherapy. The data suggest that non-specific T suppressor-cell activity is reduced in allergic patients but immunotherapy does not restore such activity.

Adverse pulmonary responses to aspirin and acetaminophen in chronic childhood asthma.

Because aspirin (ASA) is often reported to have an adverse effect on pulmonary function in children with chronic asthma, acetaminophen is commonly used as an ASA substitute in these children. To study acetaminophen effects on pulmonary functions, double-blind, oral challenges of ASA (600 mg), acetaminophen (600 mg), or lactose were administered on separate days to 25 chronic asthmatics, ten boys and 15 girls, ranging in age from 8 to 18 years (mean age +/- 1 SD: 12.5 +/- 2.8 years). No patient had a past history of adverse reactions to either drug. Forced expiratory volume in 1 second (FEV1), peak expiratory flow rate (PEFR), maximal mid-expiratory flow rate (FEF25-75), forced vital capacity (FVC), maximal voluntary ventilation (MVV), and flow volume curves were measured at base line and 1/2, 1, 2, 3, and 4 hours after ingestion of drug or placebo. Persistent decreases from base line FEV1 (greater than 20%) or FEF25-75 (greater than 30%) occurred in four ASA- and two acetaminophen-challenged patients. One ASA-sensitive patient was placebo intolerant; another reacted to acetaminophen. The acetaminophen responses were of less intensity than the ASA responses. Analysis of group mean pulmonary function responses to ASA, acetaminophen, and lactose showed no significant difference among the three agents at any time. Aspirin should be used cautiously in asthmatic children. Acetaminophen appears to be an adequate, although not completely, innocuous ASA substitute.

Levamisole in chronic pyoderma.

Eleven patients, 8 females and 3 males, aged 17-53 years with chronic recurrent pyoderma (mean duration of 8.4 years) unresponsive to a variety of therapeutic modalities, were treated with oral levamisole 1 . 5-2 . 5 mg/kg/day (100-200 mg daily) for 2 consecutive days every week. Five out of eleven patients (3 males and 2 females) demonstrated one or more host defense abnormalities including impaired polymorphonuclear (PMN) chemotaxis, impaired bactericidal activity against Staphylococcus aureus, decreased in vitro lymphocyte response to Phytohaemagglutinin (PHA) and low serum IgM and IgA. Seven of eleven patients showed clinical improvement following levamisole administration for 4-11 months. Two showed complete clearance of skin lesions while on levamisole and for a year thereafter; three showed marked clearance of lesions during levamisole therapy but recurred with mild disease 6 months after termination of levamisole therapy; and two showed improvement of lesions during therapy but recurred immediately after levamisole discontinuation. Levamisole treatment was also associated with complete in vitro correction of PMN bactericidal abnormality, improvement of PMN chemotactic abnormality and augmentation of in vitro lymphocyte response to PHA. Correlation between in vitro potentiation of host defense mechanisms and clinical response was noted. Significant probable side-effects necessitating discontinuation of therapy included transient elevation of liver enzymes in 2 patients and extensive hemorrhagic skin rash in one.

Transfer factor therapy in hyperimmunoglobulinaemia E syndrome.

The therapeutic effect of transfer factor (TF) from healthy donors was investigated in two children with extensive intractable atopic dermatitis, recurrent pyogenic skin infections, hyperimmunoglobulinaemia E, defective neutrophil chemotaxis and depressed cell-mediated immunity. Striking clinical improvement was noted in both patients with disappearance of skin infections, pruritus and eczema. No new lesions have occurred 13 months after the completion of therapy in the first patient but a few new atopic lesions have reappeared after 8 months in the second. Both patients are off steroids and antibiotics. Transfer factor administration did not influence the T cell rosette number or the lymphocyte blastic transformation response, but it did cause conversion of the skin-test reactivity in both patients and correction of polymorphonuclear chemotaxis in one of them. Non clinical side-effects were noted but marked and persistent rise of serum IgE was observed in both patients. Our data suggest that patients with hyper-IgE syndrome may be benefited by TF therapy and they lend further support to the notion that T lymphocyte deficiency may be the basis of the eczema in this syndrome.