W.James Metzger

The safety of immunotherapy during pregnancy

A group of 121 pregnancies from 90 atopic mothers who had received immunotherapy during pregnancy were studied retrospectively with the use of physician or maternal questionnaires and obstetric records. The incidence of prematurity, toxemia, abortion, neonatal death, and congenital malformation was no greater than that for the general population. The offspring of the treated mothers developed allergic disease as frequently as children born into allergic families. A group of 147 untreated pregnancies of atopic mothers were similarly studied, and the incidence of those parameters were similar except for a greater incidence of abortion. The implications of these findings are discussed.

Administration of budesonide once daily by means of Turbuhaler to subjects with stable asthma

BACKGROUND Optimal management of chronic, mild-to-moderate asthma with inhaled steroids may include use of the lowest possible doses, as recommended in guidelines, and a reduction in the frequency of daily administration for greater convenience. Lower doses and once daily treatment with inhaled steroids must be rigorously evaluated in controlled clinical trials. OBJECTIVES The objective of this study was to assess the efficacy and safety of once daily treatment with budesonide in subjects with stable asthma. METHODS Once daily budesonide was assessed in 309 adult subjects, including those who were and were not using an inhaled steroid at baseline. The subjects were stratified by inhaled steroid use and randomly assigned to one of 3 treatments: 200 microgram budesonide, 400 microgram budesonide, or placebo administered by means of Turbuhaler once daily in the morning for 6 weeks. Beyond this point, treatment was continued unchanged for another 12 weeks (maintenance) in those receiving 200 microgram budesonide once daily and placebo. In those who received 400 microgram budesonide once daily, the dose was reduced to 200 microgram once daily at week 6 and held constant for the remaining 12 weeks (400/200 microgram group). Primary efficacy endpoints were mean change from baseline in FEV1 and morning peak expiratory flow. RESULTS Once daily budesonide was well tolerated and resulted in significant improvements in all efficacy endpoints, even though baselines were well stabilized. Baseline lung function was elevated with little room for improvement; however, mean increases in FEV1 during the maintenance period were 0.10 L and 0.11 L in the 200 microgram and 400/200 microgram groups, respectively, versus a decrease of -0.09 L in the placebo arm (P <.001). Results for peak expiratory flow were similar. Significant improvements in secondary endpoints, including symptoms, beta-agonist use, and quality of life, also developed with budesonide 200 and 400 microgram once daily. CONCLUSION Inhaled budesonide, in doses as low as 200 microgram, may be an appropriate introductory or maintenance dose in subjects with stable, mild-to-moderate asthma.

Polymerization of mixtures of grass allergens

Mixed grass pollen allergens were precipitated from crude grass extract by 90% saturation with ammonium sulfate. The precipitate was dissolved and polymerized with glutaraldehyde. Polymerized allergens with a molecular weight range of 200,000 to 4,000,000 were isolated. The resultant grass allergen polymers had reduced allergenicity but were capable of absorbing out IgG antibody from sera of 2 patients treated with crude grass allergens. This alteration of allergenicity was intended to reduce the ability of allergens to react with IgE-sensitized cells rather than to modify or destroy antigenic determinants. Prior exposure of allergens to phenol used as a preservative inhibited the polymerization process probably by blocking combining sites with which glutaraldehyde reacts.

Hereditary vibratory angioedema: Confirmation of histamine release in a type of physical hypersensitivity

A new syndrome called hereditary vibratory angioedema (HVA), characterized by pyruritis and angioedema at the site of a vibratory stimulus, was recently reported as a model of nonimmunologic immediate hypersensitivity. The biochemical mediator of this syndrome was not defined initially. This study now demonstrates that in vivo histamine release occurs in conjunction with the local and systemic clinical manifestations following a controlled vibratory stimulus. Histamine is suggested as the major mediator in this inherited physical hypersensitivity state.

Hypersensitivity lung disease: early diagnosis.

The early diagnosis of hypersensitivity lung disease (HLD) is important because of its progressive morbidity. It is often difficult to establish the diagnosis in the early stages because of the absence of defined symptoms. Case histories of 2 patients with pigeon breeders HLD are reported. Both patients presented with unusual manifestations of the disease: one patient was asymptomatic but had an abnormal chest radiograph; the other patient had a normal chest radiograph but experienced occasional symptoms of exertional dyspnea. Both patients had abnormal pulmonary function and precipitin bands against pigeon serum. Following inhalation challenge with pigeon serum both patients developed fever and leukocytosis, but no significant pulmonary function response was observed. In both patients pulmonary function tests returned to near normal levels after corticosteroid therapy. Early detection of HLD may prevent progressive irreversible pulmonary damage. This requires a high index of clinical suspicion and appropriate screening tests. Inhalation challenge procedures are useful in establishing the diagnosis.