Thomas E. Van Metre

Immunotherapy for cat asthma

In 22 patients with cat asthma who were highly sensitive to cat, we compared, double-blind, the effects of immunotherapy with cat-hair and dander extract (11 patients) with effects of placebo (11 patients). Patients were matched by the dose of the cat extract expressed in Food and Drug Administration (FDA) units of Fel d I (previously called cat allergen 1) required for end point reaction in intradermal skin test end point titration (STEPT), for in vitro leukocyte histamine release (LHR), and for the dose of cat extract producing a 20% fall in FEV1 (cat-extract PD20) in bronchoprovocation test. Patients were matched also for bronchoprovocation dose of methacholine producing a 20% fall in FEV1 (methacholine PD20). Patients were randomly assigned to one of two treatment groups. During immunotherapy, doses were increased to maintenance dose of 4.56 FDA units of Fel d I, or, if this were less, to the highest tolerated dose. Systemic reactions to cat-extract immunotherapy were mild and infrequent. Before and during immunotherapy, we measured (in FDA units of Fel d I) cat-extract PD20, cat-extract intradermal STEPT, cat-extract in vitro LHR, serum levels of cat IgG and cat IgE, and methacholine PD20. After they had received 1 year of immunotherapy, patients receiving cat extract, in comparison to patients receiving placebo, had decreased cat-extract PD20 (p less than 0.01), diminished responses to cat-extract intradermal STEPT (p less than 0.025), increased IgE antibodies toward cat extract (p less than 0.01), increased IgG antibodies toward cat extract, Fel d I, and cat albumin (p less than 0.001), but no significant change in cat-extract in vitro LHR or in methacholine PD20. We conclude that cat-extract immunotherapy was well tolerated, significantly decreased skin and bronchial responses to cat extract, and significantly increased IgE antibodies to cat extract and IgG antibodies to cat extract, Fel d I, and cat albumin.

Adverse effects of inhalation of excessive amounts of nebulized isoproterenol in status asthmaticus

Abstract The inhalation of excessive amounts of nebulized isoproterenol and related compounds may produce adverse effects in status asthmaticus. Nine of 17 patients, whose deaths were caused primarily by asthma, used these preparations excessively and apparently more and more to accomplish less and less. Three entered into a locked-lung syndrome when prolonged inpatient treatment with corticosteroids and all other usually employed modalities failed to produce relief of wheezing, which persisted, increased, became refractory to very large doses of isoproterenol given by hand nebulizer and intermittent positive pressure breathing apparatus, and ultimately caused death. Thirty living patients, with severe asthma resistant to all usual forms of treatment, including corticosteroids, improved when they stopped overusing nebulized isoproterenol compounds. One of these showed no bronchodilating response after recovery. One normal person had evidence of irritation of the upper and lower respiratory tract after inhalation of excessive aerosol from the Isuprel Mistometer but no evidence of bronchial obstruction. These data are consistent with the hypothesis that therapeutic doses of these preparations are well tolerated and effective against bronchial obstruction due to asthma, but overusage may induce and/or maintain irritation of the air passages and intractable asthma.

A comparative study of the effectiveness of the Rinkel method and the current standard method of immunotherapy for ragweed pollen hay fever

Abstract In a double-blind study, we compared the effects of the Rinkel and the current standard methods of immunotherapy with ragweed pollen extract and those of placebo on symptoms of ragweed hay fever and immunologic parameters in 43 patients highly sensitive to ragweed. Each had a skin-test end point by Rinkel serial titration at 1:312,500 w/v or greater dilution, a 2+ skin test to ragweed AgE 0.01 μg/ml, and in vitro histamine release by ragweed pollen extract. None had had immunotherapy for at least 7 yr. Patients were matched on the basis of leukocyte histamine release to ragweed pollen extract and assigned to treatment groups. Fourteen received ragweed pollen extract by the Rinkel method, 14 received placebo, and 15 received ragweed pollen extract by the current standard method weekly between February and October, 1979. Rinkel method doses were derived from skin-test end points and were advanced to 0.5 ml of the end-point dilution; current standard method doses were advanced to the highest tolerated dose. The median maintenance dose for Rinkel method patients was 0.5 ml of 1:1,562,500 w/v (0.001 μg AgE), and for current standard method patients was 0.3 ml of 1:100 w/v (11 μg AgE). An additional unmatched group of nine similar patients received Rinkel method immunotherapy in both 1978 and 1979. Under the conditions of this study, the current standard method of immunotherapy produced a significant decrease in ragweed hay fever symptom-medication scores, increase in antiragweed IgG levels, and decrease in seasonal rise in antiragweed IgE levels in comparison with the effects of either Rinkel method or placebo. The effect of the Rinkel method on these variates was not significantly different from the effects of placebo.

A comparison of immunotherapy schedules for injection treatment of ragweed pollen hay fever

In 44 patients highly sensitive to ragweed, we compared weekly injections of single doses of ragweed extract (RW-Wk, 15 patients) with clustered doses of ragweed extract at 3-wk intervals (RW-Cl, 18 patients) for effects on ragweed hay fever symptom-medication scores and immunologic variates. Patients were matched and randomly assigned to treatment groups. Ragweed doses were advanced to the highest tolerated dose. Doses and number of visits were lower in the RW-Cl group than in the RW-Wk group. Despite lower doses, systemic reactions were not reduced and antiragweed IgE levels increased significantly more in the RW-Cl group than those in the RW-Wk group. Both the RW-Cl and RW-Wk groups had significant increases in antiragweed IgG levels, decreases in seasonal rise in antiragweed IgE levels, and lower symptom-medication scores (p less than 0.01) in comparison with the placebo group. We conclude that the RW-Cl regimen offered no important advantage over RW-Wk. Seventeen patients had previously received Rinkel-method immunotherapy with 0.5 ml of end-point dilution of ragweed extract for 1 to 2 yr without significant clinical improvement or immunologic changes. After adequate treatment with either RW-Wk or RW-Cl, these patients had significantly lower symptom-medication scores than those of the placebo groups and immunologic changes similar to those of the entire active-treatment group. Therefore, treatment failures on Rinkel immunotherapy respond well to adequate dose immunotherapy by either schedule.

A comparison of the growth suppressive effect of cortisone, prednisone, and other adrenal cortical hormones☆

Abstract Normal linear growth was noted in all of thirteen children given sufficient cortisone over a period of six months or longer to suppress asthma. Linear growth suppression was noted in twelve of thirteen children given prednisone, five of nine given methylprednisolone, the two given fluprednisolone, and in the one given triamcinolone, when sufficent corticosteroid was given for a similar period of time to produce the same degree of suppression of asthma. Evidence is presented indicating that cortisone is about one fifth as potent as prednisone and one sixth as potent as methylprednisolone as a therapeutic agent in asthma, but only one tenth as potent as each as a growth inhibiting agent.

Growth suppression in asthmatic children receiving prolonged therapy with prednisone and methylprednisolone

Abstract Growth suppression was noted in twelve of thirteen asthmatic children receiving sufficient prednisone or methylprednisolone for six months or longer. Evidence indicating that this growth retardation could be logically attributed to the corticosteroid therapy is presented.

Disodium cromoglycate, a new compound for the prevention of exacerbations of asthma

Abstract Disodium cromoglycate (Intal, FPL 670) has been found to inhibit the broncho-spastic response to inhaled antigens in asthmatic patients. Its efficacy in the treatment of bronchial asthma was studied by a double-blind crossover method in 22 patients with persistent, perennial asthma. Each patient received either 2 weeks of disodium cromoglycate, by inhalation 4 times a day, followed by 2 weeks of placebo or the reverse. Daily diaries of symptoms and medication use were kept by each patient so that scores could be calculated from these diaries. Weekly physical examinations, FEV 1 , sputum cultures, blood chemistries, liver function tests, and urinalyses were obtained. Accumulated scores showed that 15 out of 22 patients improved on disodium cromoglycate. Two of the 15 patients had dramatic improvement whereas 13 patients had variable degrees of mild improvement. Analysis of variance showed that the difference between the treated and placebo periods was significant at the 2 per cent level. No untoward side effects were noted.

Pain and dermal reaction caused by injected glycerin in immunotherapy solutions

BACKGROUND Fifty percent glycerin preserves immunotherapy solution potency for at least 3 years but must be diluted before injection to reduce glycerin-induced pain and inflammation. We studied pain, erythema, induration, and bruises caused by glycerin (0% to 30%). METHODS In 15 healthy subjects we compared, in double-blind fashion, pain scores, injection site erythema, induration, and bruising caused by subcutaneous injections in randomized order of 0.1, 0.5, and 1 ml of glycerin 0%, 10%, 20%, and 30%. RESULTS Injection volume did not significantly influence pain scores from diluent alone (0% glycerin) (p greater than 0.1). Pain scores of subjects given glycerin (0.1 to 1 ml, 10% to 30%) increased significantly as both injection volume (p less than 0.001) and glycerin concentration (p less than 0.001) increased. Pain scores correlated with total glycerin dose administered (volume x concentration) (rs = 0.67, p less than 0.0005) but varied widely, from minimal to severe, in those given the same dose. Injection site erythema, induration, and bruising occurred in some subjects with significant positive correlations between total glycerin dose and both frequency and diameters of erythema and induration. However, these dermal reactions were of trivial clinical importance. CONCLUSION Injected glycerin produces pain that is proportional to total injected dose of glycerin, but individual variation in perceived discomfort is substantial. Total glycerin doses of less than 0.05 ml rarely produce clinically important pain.

EVIDENCE OF ALLERGY IN PATIENTS WITH CYSTIC FIBROSIS OF THE PANCREAS

Abstract Review of the records of 135 patients with cystic fibrosis of the pancreas revealed that nineteen had evidence of atopic allergy. The diagnosis of cystic fibrosis was easily overlooked in patients with classical manifestations of atopic allergy, such as asthma, nasal polyps, hay fever, urticaria, eczema, positive skin tests, and familial allergy. Optimal therapy for many of these patients included treatment of the allergic problem as well as the usual regiment for cystic fibrosis. Forty-seven patients with atopic bronchial asthma had no evidence of the sweat chloride abnormality characteristic of cystic fibrosis of the pancreas. The nature of the relationship between cystic fibrosis of the pancreas and atopic allergy is not clear.

The relation between nongranulomatous uveitis and arthritis

Abstract Arthritis occurred in 20 (30 per cent) of 67 patients with nongranulomatous uveitis, but in only 8 (3 per cent) of 277 patients with other uveal lesions. It was more common in patients wth recurrent, acute rather than persistent, chronic nongranulomatous uveitis. The arthritis had distinctive features. It was usually an asymmetrical, nonankylosing, peripheral polyarthritis involving the lower extremities more frequently than the upper ones. In addition, ankylosing spondylitis was present in almost all male but in no female arthritis patients. Rheumatoid factor could not be demonstrated in the sera of these patients. The data suggest a relation between nongranulomatous uveitis and a distinctive type of arthritis.