Clinical and nasal biopsy response to treatment of perennial rhinitis

Nasal biopsies of patients with perennial rhinitis were performed at baseline and compared with biopsies performed 4 wk after active flunisolide, 50 μg four times per day, or placebo. An effort was made to relate histologic findings to other subjective and objective parameters as an indication of response to treatment. Although patients admitted to the study had severe subjective nasal symptoms, biopsies varied considerably. Some resembled biopsies from normal individuals, and others showed marked edema and inflammation; the latter findings were more typically present in the biopsies of patients with the most severe disease. A decrease in edema and loss of inflammatory cells on biopsy as well as a corresponding decrease in eosinophils on the nasal smear usually accompanied clinical improvement, which occurred in both the active and placebo groups.     

A comparison of methacholine and histamine inhalations in asthmatics.

Bronchial provocation tests using aerosolized serially diluted histamine and methacholine were given to nearly 200 asthmatics. Results were usually reproducible for a given patient and corticosteroids did not influence the procedures. Those patients who could tolerate high doses of methacholine were statistically the least severe asthmatics as measured by their discharge dose of corticosteroids. Reaginmediated asthmatics could not tolerate the higher doses of histamine. These tests help delineate subgroups of asthmatics and may have clinical usefulness since, when combined with other data, they differentiate pathogenetic mechanisms in some patients and suggest therapeutic approaches in others.     

Effect of bronkosol and its components on cardiopulmonary parameters in asthmatic patients.

Bronkosol and its components, isoetharine hydrochloride and phenylephrine hydrochloride, were compared in a double-blind randomized fashion for their effect on pulmonary and cardiovascular parameters in patients with reversible bronchospasm. Bronkosol and isoetharine produced significant bronchodilatation as measured by forced expiratory volume in one second (FEV), forced vital capacity (FVC), and mean forced expiratory flow during the middle half of the FVC (isovolume FEF 25% to 75%), and phenylephrine did not. There was no difference between Bronkosol and isoetharine in the degree or duration of bronchodilatation. Significantly more patients had to "discontinue" after 15 min on the day of testing with phenylephrine than with Bronkosol or isoetharine. Heart rate was not increased after Bronkosol or isoetharine, confirming its selective beta-2 action. The addition of phenylephrine to isoetharine had no beneficial effect on oxygen saturation. There was no significant difference between these drugs in systolic and diastolic blood pressure, pulse, or respiration. The results of this study cast doubt on the useful contribution of phenylephrine in Bronkosol.     

Dose-response effects of albuterol aerosol compared with isoproterenol and placebo aerosols: response to albuterol, isoproterenol, and placebo aerosols.

Albuterol aerosol was an effective bronchodilator as reflected by indices of pulmonary function obtained from spirometry and flow volume curves; Compared with isoproterenol, there were minimal side effects even at the highest doses, and bronchodilation lasted significantly longer. In addition albuterol was successfully used by a patient with idiopathic hypertrophic subaortic stenosis who was unable to tolerate isoproterenol, as well as by some patients with idiosyncratic responses to isoproterenol; A few patients appeared to derive little benefit from either albuterol or isoproterenol.     

The use of humidity in asthmatic children.

Controversy exists as to the advisability of mist therapy in pulmonary disease. We studied the effects of several forms of humidity on asthmatic airways. Thirty-four children were tested over a period of 8 months as follows: (1) mist with a mean particle size of 3 mu was delivered for 30 min by an ultrasonic nebulizer to 11 children individually in a plastic tent; (2) to another 11 subjects in a tent, mist with a mean particle size of 10 mu was delivered by a jet nebulizer for 30 min;3) 15 patients in a croup room recieved for 30 min water droplets ranging from a microscopic fog to large rain particles (mean 16 mu) generated by a Melco natural fog generator; (4) 10 children were challenged with 3 solutions used commonly for the production of mist: distilled water, half-normal saline, and normal saline. Pulmonary functions were studied on each patient pre- and post-mist exposure. Approximately two thirds of the patients had a significant response, either improvement or deterioration, when challenged with the various forms of mist. No particular group trends were produced either by increasing the mean particle size of humidity, or by using solutions of increasing salinity.     

Objective clinical and laboratory studies of immediate hypersensitivity reactions to foods in asthmatic children.

Clinical and laboratory observations were made with 38 children afflicted with chronic severe asthma (reversible obstructive airway disease) in which hypersensitivity to food was incriminated in the histories. Symptoms were evoked in double-blind food challenges in only 11/38 children and 14/70 challenges, and were characteristic of immediate-type hypersensitivity and were chiefly gastrointestinal, even though asthma was the common presenting complaint. There were no delayed reactions. Peanut was responsible for 8 reactions, egg for 5, and cow's milk for 1. The feature that most successfully identified those having positive reactions in challenges was a significant wheal reaction in a skin test by puncture technique using a verified extract of 1:20 W/V concentration. No subject with clinically significant, symptomatic hypersensitivity to food had a negative puncture test, and puncture tests were positive in only 10/56 instances of negative reactions in food challenges. Laboratory observations included release of histamine and enzymes from leukocytes and the levels of neutrophil enzymes in serum before and after food provocation tests. While these determinations were of interest with respect to the immunochemical basis of reactions to foods, they did not prove useful for practical clinical diagnosis. The outstanding laboratory findings was the occurrence of "spontaneous" release of 25% to 100% of the histamine from leukocytes in all cases proved clinically hypersensitive by food challenges, which suggests that this may be an indicator of immediate-type hypersensitivity to food. From the findings in the study, a general approach to food hypersensitivity was developed in which the immunologic components coupled with quantitative concentration-response relationships serve to render comprehensible the distinction between asymptomatic (immunologic) hypersensitivity and symptomatic (clinical) hypersensitivity.     

Comparative effects of ephedrine on adrenergic responsiveness in normal and asthmatic subjects.

A comparison was made of the metabolic and pulmonary responses to adrenergic stimulation in 6 normal subjects and 10 patients with mild asthma who were treated with equal amounts of ephedrine for 7 to 10 days. During the control and placebo periods, the measurements of cyclic adenosine monophosphate (AMP) in leukocytes of asthmatic subjects were similar to those of normal subjects. After one week of therapy with ephedrine, both groups exhibited suppression of the leukocyte cyclic AMP responses to adrenergic stimulation in vitro; however, the suppression of response was significantly greater in asthmatic subjects (p < 0.01). The plasma glucose responses to administered epinephrine also decreased in both groups after treatment with ephedrine, but the change occurred earlier in asthmatic subjects. Ephedrine did not alter either the baseline pulmonary functions or the pulmonary responses to administered epinephrine; however, significant changes in pulmonary function were not observed after subcutaneous administration of 200 μg of epinephrine during any of the treatment periods. Morning plasma cortisol concentrations were significantly lower in asthmatic patients than in normal controls (p < 0.001) but were not affected by treatment with ephedrine. Administration of 100 mg of Solu-Cortef intravenously improved the glucose responses to epinephrine in ephedrine-treated asthmatic subjects but did not influence the pulmonary responses or the measurements of leukocyte cyclic AMP in either group. The results indicate that the metabolic responses to adrenergic stimulation are markedly altered in both normal and asthmatic subjects by a short period of treatment with ephedrine. However, loss of metabolic response was not associated with corresponding changes in the pulmonary responses to therapy.     

High spontaneous release of histamine in vitro from leukocytes of persons hypersensitive to food.

In vitro studies of antigenic release of histamine from peripheral leukocytes (basophils) have been done in more than 600 allergic children. Ordinarily only about 5% to 10% of the histamine content of leukocytes will leak out or be released "spontaneously" during incubation of suspensions in vitro, without the addition of antigen. A small percentage of children were found to have leukocytes that released 25% to 100% of the histamine content spontaneously during incubation. The significance of this was not apparent until recently, when studies were concentrated on children suspected of hypersensitivity reactions to foods, among whom a much greater prevalence of spontaneous histamine release from leukocytes was encountered. Of children proved by a double-blind food challenge to react with manifestations of immediate hypersensitivity, 100% had leukocytes that consistently released over 25% (usually between 50% and 100%) of the histamine content spontaneously without the addition of antigen. Such high spontaneous histamine release appears to be characteristic of persons with clinical evidence of hypersensitivity to food.     

Studies of hypersensitivity reactions to foods in infants and children

In order to extend previous investigations of adverse reactions to foods performed at this institution, 68 children, aged 5 mo to 15 yr, were studied. All subjects reported a history of adverse reaction to ingestion of one or more of the 14 foods under study. Sixteen of 43 subjects, 3 yr of age or older, had 22 adverse reactions during 94 food challenges with one or more of the 14 foods. All reactions confirmed were to peanut or other nuts, milk, egg, and soy. Skin testing with 1:20 weight/volume concentrations of food extracts applied by the puncture technique produced a net wheal reaction 3 mm or greater in all subjects 3 yr of age or older in whom double-blind food challenges confirmed the history of adverse reaction. Thirteen of 25 children less than 3 yr of age manifested adverse reactions during 49 food challenges. Skin testing by puncture technique produced a net wheal 3 mm or greater in 9 children less than 3 yr of age in whom food challenge elicited a clinical response within 2 hr. One of 4 subjects less than 3 yr of age in whom the adverse reaction occurred more than 4 hr after food challenge exhibited a wheal to puncture skin test of 3 mm or greater. These studies suggest that at present double-blind food challenge is an indispensible tool for the unequivocal evaluation of adverse reactions to foods.     

Effect of a selective beta 2 adrenergic agonist and theophylline on skin test reactivity and cardiovascular parameters.

Fenoterol, a selective beta 2-adrenergic agent, and aminophylline in the "therapeutic range" were compared with placebo for their inhibitory effect on skin test reactivity to allergens and histamine. Cardiovascular parameters were also assessed. A new, inexpensive micrometer adaptor to a tuberculin syringe was used to deliver allergens and histamine more accurately. No inhibition of skin test reactivity to antigens or histamine was found after a loading dose or after 1 wk of round-the-clock therapy with these bronchodilators. Although there was increased heart rate after 1 and 2 hr with fenoterol, there was no patient preference for one bronchodilator over the other. The results of this study point out some of the difficulties in trying to extrapolate in vitro findings to in vivo correlates since neither fenoterol nor therapeutic doses of theophylline interfere with immediate skin test reactivity.     

Pulmonary function studies with simple equipment in 323 normal children

Frequent testing of pulmonary function in patients with obstructive pulmonary disease with the use of simple equipment is helpful in following the course of the disease. In order to provide normal values valid at the altitude of Denver, Colorado (5,280 feet), pulmonary function data in 323 healthy children and adolescents ranging from 4 to 18 years of age have been obtained using two inexpensive instruments, the Jones Pulmonor spirometer and the Wright peak flow meter.     

Treating depression in asthmatic patients

Asthma patients frequently develop depression, especially when treated with high-dose corticosteroids. Depressed asthmatics should be promptly treated, since depression frequently decreases compliance. Antidepressants containing the dye tartrazine should be avoided because tartrazine may provoke bronchospasm. Patients may benefit to a mild degree from the anticholinergic effects of some antidepressants, but monoamine oxidase inhibitors (MAOIs) should be avoided in those who are receiving epinephrine injections or several other drugs commonly used to treat rhinitis and sinusitis. To avoid the risk of decreasing respiratory drive, caution should be exercised when combining high dosages of sedating antidepressants with sedative-hypnotics and antianxiety agents.     

Growth of asthmatic children during treatment with alternate-day steroids

The effects of specific doses of alternate-day treatment with prednisone on linear growth were evaluated in children with severe asthma. It was found that even the control patients who did not receive steroid therapy had heights that were significantly lower than those of normal children of the same age and sex. The average severity of growth suppression in children who received alternate-day or intermittent treatment with steroids did not differ from that of asthmatic control patients. However, evaluation of individual patterns of growth during the follow-up period revealed that children who received small doses of alternate-day treatment (mean dose of prednisone, 9 mg. q.o.d.; range, 2.5 to 14 mg.) had acceleration of growth, whereas children who received larger treatment doses (mean dose of prednisone, 30 mg. q.o.d.; range, 18 to 58 mg.) had further suppression of growth during the period of study. Additionally, patients who had previously been treated with daily corticosteroids failed to demonstrate “catch-up” growth after introduction of an alternate-day program (mean dose of prednisone, 17 mg. q.o.d.).     

Drug abuse and the asthmatic patient: a case report

The case history of a 17-year-old girl with sudden onset of theophylline toxicity and a serum theophylline concentration of 63 micrograms/ml is presented. A change in theophylline elimination was not sufficient to explain this observation. Subsequently, the patient admitted to recent self-medication with several over-the-counter medications and illicit drugs. Although the etiology of theophylline toxicity in this patient could not be defined, several theories are proposed. Included is a discussion of possible interactions of illicit drugs with asthma medications and a summary of personality characteristics associated with a high potential for drug abuse.     

Evaluation of a patient with both aquagenic and cholinergic urticaria

An 11-yr-old girl presented with a history of urticaria induced by warm or cool showers, exercise, and emotional stimuli. During evaluation she repeatedly developed generalized punctate urticaria, pruritus, palpitations, and headaches after warm baths or exercise, and she had a positive methacholine skin test. She developed similar lesions and pruritus after local application of sterile water, tap water, ethanol, normal saline, or 3% saline. The diagnosis of combined aquagenic and cholinergic urticaria was made and presented a unique opportunity to study and compare mediator release and clinical symptoms in both conditions. The patient was submerged in bath water at either 37° or 41° C to induce either aquagenic or cholinergic urticaria, respectively. Histamine was released into the systemic circulation in both condition in a similar time course; however, systemic symptoms occurred only after the 41° C bath. After failure to induce tolerance to the 41° C bath water, hydroxyzine therapy was instituted. One week later she was rechallenged; few symptoms appeared, and a rise in serum histamine was not detected as had been shown in previous challenges. The data suggest that in our patient, hydroxyzine may have contributed to the inhibition of both histamine release and the appearance of symptoms during hot bath challenging.     

Effect of phenobarbital on theophylline disposition

The effect of chronic phenobarbital administration on the pharmacokinetics of theophylline was studied in 6 healthy, nonsmoking adults. Subject compliance was verified by the determination of plasma phenobarbital levels. Following four weeks of phenobarbital administration, all six subjects showed a resultant increase in serum clearance varying from 11% to 60% with a mean increase of 34% (from 3.01 to 4.04 L/hr/1.73 M2). Theophylline appears to be metabolized more rapidly during chronic phenobarbital administration. This effect, therefore, must be taken into account when administering barbiturates to asthmatic patients for whom theophylline therapy is prescribed.     

Panic-fear in asthma: Requests for as-needed medications in relation to pulmonary function measurements

Requests for as-needed medications and treatments (PRNs) by asthmatic patients scoring high, moderate, or low on the Asthma Symptom Checklist panic-fear category were studied for days when patients were matched at normal, intermediate, and subnormal levels of pulmonary function. Low panic-fear patients were the least likely to request PRNs regardless of the pulmonary function level. In contrast, high panic-fear patients often requested PRNs at each level of pulmonary function. Only moderate panic-fear patients made progressively more PRN requests on days when pulmonary functions were lower. These observations and others concerning the adverse influence of extreme panic-fear coping styles upon the treatment of asthma were discussed.