James A. McLean

Standardization of bronchial inhalation challenge procedures

A group of investigators interested in the standardization of inhalation challenge techniques was selected by the program directors of the Asthma and Allergic Disease Centers (AADC). This effort has been assisted by the National Institute of Allergic and Infectious Diseases of the National Institutes of Health. At the last meeting of the panel on February 15, 19’75, criteria for procedures and materials used were suggested in order to standardize bronchial inhalation challenges as they pertain to allergic disease.

Measurement of nasal airway resistance

Abstract A measure of nasal airway resistance can be obtained by simultaneously relating transnasal pressure drop and the rate of nasal air flow. Resistance varies continuously throughout the range of attainable flows, and it has meaning only in relationship to specified rates of flow at which it is measured. The procedure described appears to provide a usable objective parameter for evaluating nasal response to controlled allergenic challenge and to other test situations.

Effect of histamine and methacholine on nasal airway resistance in atopic and nonatopic subjects: Comparison with bronchial challenge and skin test responses

Serial nasal, intracutaneous, or bronchial challenges were carried out with solutions containing 2- or 3-fold increments in histamine (H) or methacholine (Meth) concentration until nasal airway resistance (NAR) increased by more than 100%, a large intracutaneous reaction was elicited, or FEV1 decreased by 20% or more. Thirty nonatopic and 48 asymptomatic atopic subjects were studied, the latter group divided into rhinitic patients with and without asthma. Several types of data analysis demonstrated there was no significant difference in the nasal or cutaneous effects of H or Meth between the atopic and nonatopic groups. Comparable results were obtained in a subgroup of 39 subjects (13 normal, 13 atopic, and 13 atopic with asthma) who underwent all six test sequences (i.e., nasal, cutaneous, and bronchial with both drugs). As expected, the asthmatics showed significantly increased bronchial reactivity to both agents. In comparison with Meth, H had a much greater effect on the nasal mucosa and skin than on the bronchi. It is concluded that, contrary to bronchial responses, but in accord with cutaneous reactivity, the nasal responses of nonatopic subjects, atopic persons with allergic rhinitis alone, and subjects with both allergic rhinitis and asthma show no intergroup differences on testing with H or Meth.

A study of relationships between family situation, bronchial asthma, and personal adjustment in children.

Summary The first phase of a research project on childhood asthma carried out jointly by allergists at the University of Michigan Medical Center and child psychiatrists at Hawthorn Center is described. The focus of the present investigation is the relationship between family psychological situation and the childs asthma situation. Seventy-one children with chronic bronchial asthma and their families were studied to test the following hypothesis: A study of asthmatic children and their families will reveal a positive relationship between the asthma situation (onset, severity, response to treatment) and the family situation (quality of family relationships, identification opportunities, and care and handling). As a control a second hypothesis was tested: A study of the same group of children and their families will reveal a positive relationship between level of disturbance in the childs personality and/or behavior, and level of disturbance in family relationships, and care and handling. The patients were drawn from the regular office and clinic patients of practicing allergists. The asthma situation was studied with emphasis on severity, course, and response to medical management over a period of at least 2 years. Psychiatric study involved individual interviews with each parent and with each patient and systematized recording of findings. Seventy-one variables relating to family situation, the childs adjustment, and asthma situation were recorded for statistical analysis. Three statistical assessments of the data were made: 1. Exploration of relationships between variables. No significant relationships between variables of the family situation and those of the childs asthma are found. In contrast, there is frequent occurrence of significant correlation of variables of the family situation and those of the childs adjustment. Thus the first hypothesis is not supported, while the second hypothesis is strongly supported. 2. Comparison of 2 subgroups representing extremes of family adjustment, including relationships, stability, and child care. The 20 families showing best adjustment and the 20 families showing poorest adjustment are compared on 23 variables including those dealing with severity of asthma and response to treatment. The independent grouping of subjects is confirmed by consistently significant contingencies for all variables concerned with family adjustment. The first hypothesis is not supported; no differences are found between the 2 extreme groups on the asthma variables. The second hypothesis is strongly supported; there is positive relationship between family pattern and child personality and adjustment. 3. Three groups differentiated on the basis of good, moderate, and poor family situation are compared on the changes shown in severity and response to treatment from initial to follow-up status. None of the 3 groups shows significant differences from each other in pattern of changes. All these statistical explorations lead to the conclusion that, in the areas of severity of asthma and response to treatment, no relationships with family situation are demonstrable. On the other hand, close relationships between family situation and childs adjustment are consistently demonstrated by the findings. Child psychiatry is seen to have a selective role in the treatment of the asthmatic child. Routine referral is unnecessary. On the other hand, the disturbed asthmatic child requires psychiatric help, and medical-psychiatric treatment is clearly indicated for a good many of the parents. The deciding factor is not the childs asthma but the emotional status of both child and family, with the recognition that the asthma may add new problems requiring therapeutic intervention through the coordinated efforts of allergists, child psychiatrists, and case workers.

Priming of the nasal mucosa by ragweed extract or by an irritant (ammonia)

Confirming previous work by Connell, it was shown that challenging nine subjects intranasally on successive days with short ragweed extract (SRW) resulted in a priming effect manifested by significantly augmented increases in nasal airways resistance as well as in increasing subjective symptoms. Priming was reproducible and transient. In contrast, significant priming to an irritant, ammonia gas (NH3), could not be unequivocally demonstrated over a similar period of time in these same subjects under the conditions employed. Also, priming these subjects with SRW extract failed to enhance responsiveness to NH3.

The effects of topical saline and isoproterenol on nasal airway resistance

Following determination of baseline nasal airway resistance (NAR) in human subjects, phosphate-buffered saline (PBS) was aerosolized into each nostril and NAR measurements repeated 8 times in 15 minutes. The mean maximal NAR increase in 102 subjects was 22.5% (SD +/- 24.5%) with no significant difference between atopic and nonatopic persons. Hay fever patients did not show significantly increased responsiveness to PBS while symptomatic. During 242 repeat challenges with PBS in 67 asymptomatic subjects, NAR increased over 50% in 24 tests. Following a series of 6 PBS challenges at 15-minute intervals, 10 of 71 subjects had more than a 100% increase in NAR over initial baseline values. Administration of PBS on cotton pledgets, pipetting PBS into the nose, or even just inserting a nasal speculum produced greater increases in NAR than the usual aerosol method. Intranasal atropine effectively blocked PBS-induced increases in NAR, suggesting parasympathetic stimulation as a mechanism. Isoproterenol increased NAR over 100% in 27 of 53 subjects, with no significant difference among rhinitic, asthmatic, and nonatopic individuals. This effect was inhibited by propranolol. Isoproterenol administration to 12 ragweed-sensitive subjects 15 minutes prior to ragweed challenge produced a variable inhibition in NAR responses or no protection at all. Thus the direct effects of isoproterenol on the nasal vasculature tend to outweigh those expected from inhibition of mediator release under the conditions of this study.

An improved technique for nasal inhalation challenge tests

An improved technique for nasal inhalation challenge tests is described. It includes an improved delivery system utilizing a Maxi-Myst air compressor delivering a flow of room air controlled by an in-line, electroncially timed solenoid which precisely controls the duration of compressor activity. A No. 251 DeVilbiss atomizer will deliver 0.1 + 0.01 gm/spray when the flow rate is 11.5 L/min, the duration of atomizer activity is approximately 0.1 sec, and the amount of liquid in the atomizer insert is kept between 0.75 and 2.0 ml. Nasal aerosol challenge of 0.1 ml of isotonic phosphate-buffered saline per nostril produced less variability in nasal airway resistance (NAR) response than 0.2 ml, and the smaller volume proved satisfactory for 6 consecutive saline challenges at 15-min intervals. A new face mask, which did not impinge on the bridge of the nose or paranasal structures, yielded lower baseline values of nasal airway resistance and much less variability in these measurements. Techniques employed in objectively quantitating nasal responses to various exogenous substances are briefly but critically reviewed.

Effects of aspirin on nasal responses in atopic subjects

Preliminary experiments indicated that solutions of aspirin (ASA) in buffered saline, pH 7.35, did not significantly change nasal airways resistance (NAR) when 0.1 ml of solution containing 22.5 mg (or less) per deciliter was sprayed into each nostril. Subsequently it was shown that this quantity of ASA administered intranasally did not significantly change NAR responses 15 min later to intranasal administration of increasing concentrations of histamine, methacholine, or an irritant (NH3 gas). However, the same atopic subjects demonstrated significantly decreased responses to intranasal challenge with short ragweed extract (SRW) after intranasal ASA. In addition, prior oral administration of ASA, Na salicylate, and indomethacin significantly inhibited nasal challenge responses to SRW in sensitive subjects under controlled conditions.

Controlled Studies of Intranasal Immunotherapy for Ragweed Pollenosis

During 1978 a double blind study compared the efficacy of preseasonal short ragweed (RW) extract intranasal immunotherapy with a histamine placebo; in 1979 more prolonged treatment with a larger dose of polymerized ragweed (PRW) was evaluated. In neither year did the placebo-treated patients show significantly more severe disease as assessed by daily symptom diaries, examination in season, comparison of overall symptom severity with previous years or changes in nasal challenge tests. Following treatment in 1979 there was a significantly greater amount of secretory IgA and IgG ragweed antibodies secreted by the nose of the PRW-treated group, but these titers did not correlate with clinical results.

Studies on insect sting hypersensitivity: I. Precipitin-in-gel tests and passive cutaneous anaphylaxis

Abstract Precipitin-in-gel tests to honey bee, yellow jacket, wasp, and hornet antigens with sera from 26 patients who had had clinical reactions to Hymenoptera insect stings were negative, as were sixteen control sera. Passive cutaneous anaphylaxis in guinea pigs gave positive reactions to thirteen of the 26 sera when honey bee antigen was used and to three of the 26 with yellow jacket antigen. No PCA reactions were elicited with wasp or hornet antigens. The presence of antibodies capable of giving a PCA reaction did not correlate with the severity of the clinical response to the insect sting, the skin test reactions, or the specificity of the insect identified as causing the reaction. The possible significance of these results to the etiology of the reactions is discussed.