- Email: [email protected]
Late asthmatic reactions (LAR) in ragweed pollen sensitivity
VOLUME 51 NUMBER 2
Abstracts of papers
95
or 4 inhalations at 25 mg. per milliliters was noted in 106 of 121 patients with good histories of asthma. This incidence was significantly different (p ~ 0.01 by X2) from that (22 of 139) of a mixed group of individuals without a history of asthma. These latter included 3 of 38 with vasomotor rhinitis who showed a bronchospastic response, 9 of 36 with allergic rhinitis, 10 of 24 with chronic bronchitis, zero of 21 with other respiratory diseases, and zero of 20 without respiratory disease. Among patients with a history of asthma and chronic bronchitis, 15 of 18 had bronchospasm following methacholine. Among those with chronic bronchitis without a history of asthma, 10 of 24 had a bronchospastic response (p ~ 0.01 by x2). Although these results confirm the apparent usefulness of methacholine inhalation as a diagnostic test for bronchial asthma, the incidence of false negatives and positives, particularly in patients with rhinitis or bronchitis, suggests that it is not an infallible test. 36.
Priming phenomenon in the lung.
R i c h a r d R. R o s e n t h a l , M.D., a n d P h i l i p
S. N o r m a n , M.D., B a l t i m o r e , M d . Priming, or increased sensitivity to antigen following exposure, has been described in the nose using whole ragweed pollen. Priming has not been demonstrated in the lung and could play a role in asthmatic symptomatology during seasonal pollen exposure. It is also an important consideration in the design of any experimental protocol requiring serial bronchoprovocations with antigen. Thirteen patients with a history of both asthma and hay fever symptoms during the ragweed pollen season and a positive skin test to ragweed extract were selected. Patients were given bronchial challenge out of season on 4 successive days by serial inhalation of 2, 5, 10, 30, and 40 breaths of the lowest concentration of ragweed extract that produced a positive skin test. Patients were monitored in the variable pressure plethysmograph, and a drop in conductance of 40 per cent or peak flow of 20 per cent sustained for 10 minutes was considered a positive response. In non-responders challenge was continued with a tenfold increase in antigen concentration. All patients responded when an adequate dose was reached. Two patients required 2 rag. atropine sulfate intravenously in order to ablate nonspeeific bronchospastic responses. Antigen dose-response curves were drawn, and the cumulative dose required for a 35 per cent reduction in airway conductance was calculated and designated Provocation Dose (PD) 35. In 2 cases challenge had been terminated before a 35 per cent drop in conductance, and these curves were extrapolated to 35 per cent. In every case, the PD35 on any one day was within one log of that on any other day. No regular trend toward either priming or desensitization was noted. The daily changes in antigen sensitivity did not correlate with daily baseline variation. To determine if there was any priming due to natural exposure to pollen, 9 patients were brought back and rechaJlenged during the pollen season. Baseline airway conductance values were no lower than observed out of season, and there was no significant increase in bronchial sensitivity to ragweed extract. In this limited experience priming could not be demonstrated in the lung in patients with bronchial sensitivity to ragweed antigen as a result of either laboratory or natural exposure. The PD35 method provides figures useful for comparing dose response curves and shows a one log variation from day to day. Any evaluation by bronchial challenge of antigen sensitivity or drug efficacy must take into account such variation.
37. Late asthmatic reactions (LAR) in ragweed pollen sensitivity. A. T. K e r i g a n , D. R o b e r t s o n , R. C h a l m e r s , Ontario, Canada
F. E. Hargreave,
and J. Dolovich, Hamilton,
Antigen-induced LAR are potentially representative of a major part of the pathologic processes in asthmatic attacks. An examination of the frequency and correlates of LAR was performed in 10 subjects with ragweed-induced asthmatic attacks. l~gweed pollen extract was used in skin and inhalation tests~ Subjects received inhalation challenges with antigen and control preparations in a standardized procedure. They were
96
American Academy of Allergy
J. ALLERGYCLIN. IMMUNOL. FEBRUARY1973
monitored for changes in airflow rates by spirometry and airway resistance by body plethysmography. Labeled antigen E was used to assay serum antibodies. All 10 subjects had immediate asthmatic responses to inhaled ragweed. There were LAR in 6. Between the immediate and late respenses~ there was complete recovery of airflow rates and airway resistance. Subjects with LAR were those with greatest sensitivity to ragweed; in general, less antigen was required in inhalation challenges, immediate skin test responses were larger and occurred to more dilute antigen solutions, and there were higher levels of serum IgE antibodies to ragweed antigen E. In intradermal tests, late responses were more likely to follow immediate wheal and flare responses at sites where relatively large antigen doses were injected, and, accordingly, relatively large wheal and flare responses occurred. Conclusions are as follows: (1) LAR are common after immediate responses in ragweedsensitive asthmatic subjects; (2) there was a direct relationship between the level of sensitivity and t h e tendency to antigen-induced LAR; and (8) the tendency for late cutaneous allergic responses to follow immediate responses relates directly to the intensity of the latter or the antigen dosage administered, or both.
38. Evaluation of total pulmonary resistance in infants and young children by forced oscillation technique. W i l l i a m E. Pierson, M.D., C. W. Bierman, M.D., D. E . W o o d r u m , M.D., a n d P . P . V a n A r s d e l , J r . , M . D . , S e a t t l e , W a s h . The major portion of children admitted to a hospital with status asthmaticus are under 5 years of age, and precise evaluation of pulmonary function is difficult at beet. This study was initiated to evaluate the technique of forced oscillation in measuring total respiratory resistance in infants and small children with acute asthma. The technique is based on the principle of a low frequency sine wave of pressure (resonant frequency of 3 to 7 C.P.S.) required to overcome the elastic and inertial impedances of the respiratory system that are equal and opposite, and all applied pressure is dissipated in overcoming resistance to flow. Thus with forced oscillations of resonant frequency (3 to 7 C.P.S.) superimposed on quiet breathing by mask, the ratio of pressure (P) changes to flow (V) amplitude changes will equal flow resistance (l~s) as expressed in the following formula: P V The ~ha~ges in pressure (P) and flow (V) amplitude are measured by pressure-sensitive transducers and are electronically integrated and displayed on a storage oscilloscope. Infants and young children 11 through 36 months of age were studied, and the results were as follows: Time (hr.) 0 4 24
Respi~ratory resist, ante (ova. H~O/L./sev.) 88.9 (_+ 112.) ~5.3 (_+ 0.4) 11.2 (+ 4.7)
These values are much higher than normal even for infants of this age due to the large proportion of airways resistance in the third and fourth generation airways in small children. We conclude that the forced oscillation technique offers a sensitive, direct measure of airways resistance that is rapid~ requires no patient cooperation, and allows far more precise ventilatory evaluation of infants and small children.
39. A double-blind evaluation of antibiotics in status asthmaticus. Gail G. S h a p i r o , M.D., W i l l i a m E . P i e r s o n , M.D., C. G e o r g e R a y , M . D . , P a u l V a n A r s d e l , J r . , M . D . , a n d C. W a r r e n B i e r m a n , M.D., S e a t t l e , W a s h .
P.
Infection has been considered a major predisposing factor to status asthmaticus. This study was designed to define the incidence of bacterial and viral infections in status asthmaticns and to evaluate the therapeutic value of antibiotics in this medical emergency.
Abstracts of papers
95
or 4 inhalations at 25 mg. per milliliters was noted in 106 of 121 patients with good histories of asthma. This incidence was significantly different (p ~ 0.01 by X2) from that (22 of 139) of a mixed group of individuals without a history of asthma. These latter included 3 of 38 with vasomotor rhinitis who showed a bronchospastic response, 9 of 36 with allergic rhinitis, 10 of 24 with chronic bronchitis, zero of 21 with other respiratory diseases, and zero of 20 without respiratory disease. Among patients with a history of asthma and chronic bronchitis, 15 of 18 had bronchospasm following methacholine. Among those with chronic bronchitis without a history of asthma, 10 of 24 had a bronchospastic response (p ~ 0.01 by x2). Although these results confirm the apparent usefulness of methacholine inhalation as a diagnostic test for bronchial asthma, the incidence of false negatives and positives, particularly in patients with rhinitis or bronchitis, suggests that it is not an infallible test. 36.
Priming phenomenon in the lung.
R i c h a r d R. R o s e n t h a l , M.D., a n d P h i l i p
S. N o r m a n , M.D., B a l t i m o r e , M d . Priming, or increased sensitivity to antigen following exposure, has been described in the nose using whole ragweed pollen. Priming has not been demonstrated in the lung and could play a role in asthmatic symptomatology during seasonal pollen exposure. It is also an important consideration in the design of any experimental protocol requiring serial bronchoprovocations with antigen. Thirteen patients with a history of both asthma and hay fever symptoms during the ragweed pollen season and a positive skin test to ragweed extract were selected. Patients were given bronchial challenge out of season on 4 successive days by serial inhalation of 2, 5, 10, 30, and 40 breaths of the lowest concentration of ragweed extract that produced a positive skin test. Patients were monitored in the variable pressure plethysmograph, and a drop in conductance of 40 per cent or peak flow of 20 per cent sustained for 10 minutes was considered a positive response. In non-responders challenge was continued with a tenfold increase in antigen concentration. All patients responded when an adequate dose was reached. Two patients required 2 rag. atropine sulfate intravenously in order to ablate nonspeeific bronchospastic responses. Antigen dose-response curves were drawn, and the cumulative dose required for a 35 per cent reduction in airway conductance was calculated and designated Provocation Dose (PD) 35. In 2 cases challenge had been terminated before a 35 per cent drop in conductance, and these curves were extrapolated to 35 per cent. In every case, the PD35 on any one day was within one log of that on any other day. No regular trend toward either priming or desensitization was noted. The daily changes in antigen sensitivity did not correlate with daily baseline variation. To determine if there was any priming due to natural exposure to pollen, 9 patients were brought back and rechaJlenged during the pollen season. Baseline airway conductance values were no lower than observed out of season, and there was no significant increase in bronchial sensitivity to ragweed extract. In this limited experience priming could not be demonstrated in the lung in patients with bronchial sensitivity to ragweed antigen as a result of either laboratory or natural exposure. The PD35 method provides figures useful for comparing dose response curves and shows a one log variation from day to day. Any evaluation by bronchial challenge of antigen sensitivity or drug efficacy must take into account such variation.
37. Late asthmatic reactions (LAR) in ragweed pollen sensitivity. A. T. K e r i g a n , D. R o b e r t s o n , R. C h a l m e r s , Ontario, Canada
F. E. Hargreave,
and J. Dolovich, Hamilton,
Antigen-induced LAR are potentially representative of a major part of the pathologic processes in asthmatic attacks. An examination of the frequency and correlates of LAR was performed in 10 subjects with ragweed-induced asthmatic attacks. l~gweed pollen extract was used in skin and inhalation tests~ Subjects received inhalation challenges with antigen and control preparations in a standardized procedure. They were
96
American Academy of Allergy
J. ALLERGYCLIN. IMMUNOL. FEBRUARY1973
monitored for changes in airflow rates by spirometry and airway resistance by body plethysmography. Labeled antigen E was used to assay serum antibodies. All 10 subjects had immediate asthmatic responses to inhaled ragweed. There were LAR in 6. Between the immediate and late respenses~ there was complete recovery of airflow rates and airway resistance. Subjects with LAR were those with greatest sensitivity to ragweed; in general, less antigen was required in inhalation challenges, immediate skin test responses were larger and occurred to more dilute antigen solutions, and there were higher levels of serum IgE antibodies to ragweed antigen E. In intradermal tests, late responses were more likely to follow immediate wheal and flare responses at sites where relatively large antigen doses were injected, and, accordingly, relatively large wheal and flare responses occurred. Conclusions are as follows: (1) LAR are common after immediate responses in ragweedsensitive asthmatic subjects; (2) there was a direct relationship between the level of sensitivity and t h e tendency to antigen-induced LAR; and (8) the tendency for late cutaneous allergic responses to follow immediate responses relates directly to the intensity of the latter or the antigen dosage administered, or both.
38. Evaluation of total pulmonary resistance in infants and young children by forced oscillation technique. W i l l i a m E. Pierson, M.D., C. W. Bierman, M.D., D. E . W o o d r u m , M.D., a n d P . P . V a n A r s d e l , J r . , M . D . , S e a t t l e , W a s h . The major portion of children admitted to a hospital with status asthmaticus are under 5 years of age, and precise evaluation of pulmonary function is difficult at beet. This study was initiated to evaluate the technique of forced oscillation in measuring total respiratory resistance in infants and small children with acute asthma. The technique is based on the principle of a low frequency sine wave of pressure (resonant frequency of 3 to 7 C.P.S.) required to overcome the elastic and inertial impedances of the respiratory system that are equal and opposite, and all applied pressure is dissipated in overcoming resistance to flow. Thus with forced oscillations of resonant frequency (3 to 7 C.P.S.) superimposed on quiet breathing by mask, the ratio of pressure (P) changes to flow (V) amplitude changes will equal flow resistance (l~s) as expressed in the following formula: P V The ~ha~ges in pressure (P) and flow (V) amplitude are measured by pressure-sensitive transducers and are electronically integrated and displayed on a storage oscilloscope. Infants and young children 11 through 36 months of age were studied, and the results were as follows: Time (hr.) 0 4 24
Respi~ratory resist, ante (ova. H~O/L./sev.) 88.9 (_+ 112.) ~5.3 (_+ 0.4) 11.2 (+ 4.7)
These values are much higher than normal even for infants of this age due to the large proportion of airways resistance in the third and fourth generation airways in small children. We conclude that the forced oscillation technique offers a sensitive, direct measure of airways resistance that is rapid~ requires no patient cooperation, and allows far more precise ventilatory evaluation of infants and small children.
39. A double-blind evaluation of antibiotics in status asthmaticus. Gail G. S h a p i r o , M.D., W i l l i a m E . P i e r s o n , M.D., C. G e o r g e R a y , M . D . , P a u l V a n A r s d e l , J r . , M . D . , a n d C. W a r r e n B i e r m a n , M.D., S e a t t l e , W a s h .
P.
Infection has been considered a major predisposing factor to status asthmaticus. This study was designed to define the incidence of bacterial and viral infections in status asthmaticns and to evaluate the therapeutic value of antibiotics in this medical emergency.