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74 Simplified isocapnic hyperventilation test
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CLINICAL/BIOCHEMICAL ASSESSMENT OF ACQUIRED CTINH DEFICIENCY. A.L. Sheffer, M.D., J. Melamed, M.D., D.T. kearon, M.D., and K.F. Austen, M.D., Harvard Med. Sc h ., B oston, MA Clinical and biochemical appraisals of acquired CTINH deficiency and angioedema (AME) have been performed in 4 male and 2 female patients, ranging in age from 7 to 57, over periods ranging from 3 mos. to 6 yrs. Two had lymphatic leukemia; 1 presented initially with ANE and was found to have a lymphoma 21 mos. later. Three have had no clinically definable underlying disorder. Presenting manifestation(s) included laryngeal edema (LE) in 3, cutaneous ANE in 5, and incapacitating GI colic in 1. One required chronic prophylaxis with stanozolol for LE, 1 received periodic therapy for GI colic, and 4 have not experienced recurThe complement abnormalities rence of attacks. in all 6 included levels of CH50 which ranged from 43 to 144 U/ml (normals, 150-250); CTINH, 1.2-11.9 mg/dl (normals, 16 to 34); Clq, 5-43.8 mg/dl (normals, 35-56); and C4 protein, O-16.4 mg/dl (normals, 28-83) with means of 82.5, 3.8, 21.7 and 15.9, respectively. The mean Clq for a group of hereditary angioedema patients was 4CJ* 16 mg/dl (n = 61. Fractional catabolic rates of CTINH turnover performed in 3 patients with acquired CTINH deficiency was 5.3X, as compared to 3.5% in the hereditary form, and 2.5% in norThus, the defect in the acquired mal subjects. form is catabolic, and biosynthetic in the can hereditary form. Acquired CTINH deficiency be a paraneoplastic disorder that may precede clinical recognition of the underlying disease. The diagnosis is confirmed by reduced Clq in association with CiINH and C4 reductions.
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USEFULNESS OF ir50 IN THE INTERPRETATION OF THE METHACHOLINE INHALATION CHALLENGE TEST. W. E. Imber, M.D., C. E. Reed, M.D., R. E. Hyatt, M.D. P. W. Welsh, B.A., Eliseo Anorve-Lopez, M.D., K. Offord, M.S., B. .I. Dain, B.A., and E. Frigas, M.D. Rochester, Minnesota A decrease in FEVl of 20% or greater after methacholine challenge is a widely used criterion of asthma. The forced expiratory flow at 50% Of vital capacity ($50) is a sensitive, effortindependent measure of air flow. Over a g-year period, 473 patients at the Mayo Clinic with normal baseline spirometry received a methacholine inhalation challenge test. In this population, 102 (22%) had a decrease in FEVl of less than 20% concomitantly with a decrease in i50 of greater than 20%. Among this subgroup, 41 (50%) were diagnosed as asthmatic (Group A) at the initial visit or on follow-up 1-11 years later, 21 (25%) were diagnosed as nonasthmatic (Group B) and 20 (25%) had a clinical presentation suggestive of asthma but not sufficient at the time of examination or follow-up to warrant the diagnosis (Group C). A significant correlation between AFEVl and At50 after methacholine challenge was found (0.89, p < 0.0001). These results indicate that measurement of V50 during methacholine challenge when used in conjunction with the history and physical examination may serve to identify a group of asthmatics which otherwise would not have been detected by the FEVl criterion alone. In addition, a borderline group (C) is described in which more intensive follow-up may be indicated in order to detect the evolution of asthmatic symptoms not present on initial examination.
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SIMPLIFIED ISOCAPNIC HYPERVENTILATION TEST. Y.Y. Phillips, M.D., J.J. Jaeger, Ph.D., R.R. RosenB.L. Laube, B.A., and P.S. Norman, thal, M.D., Washington, D.C. and Baltimore, Maryland a, We wish to describe a greatly simplified system which can provide significant levels of respiratory heat exchange (RHE) in asthmatics. A single dry gas mixture consisting of 4.9% CO2 in air is delivered through a rotameter to a target balloon at any desired flow rate. When multiple measurements (n=llO) were made on 19 normal subjects at voluntary ventilatory rates (VE) of 40 to 105 l/min we observed the average FetC02 to be 0.0585 + 0.0012. Next, a group of 7 patients with exercise induced asthma (EIA) were challenged with a standard exercise protocol ventilating ad libitum from a source of dry air at room temperature.. RHE was computed and on another day the same VE was required of them using the simplified isocapnic hyperventilation (IH) scheme. The average RHE for the exercise challenge was -1.5 + 0.4 Kcal/min and for the IH challenge -1.5 5 0.5 Kcal/min (p>O.20 by paired student t The maximum fall in FEVl after the exertest). cise challenge was 29 + 5% and after IH 29 2 10% The maximum falls in SGaw were 62 + (PbO.90). 14% and 73 + 9% after exercise and IH respectively (p>O.lO). We conclude that a simplified RHE challenge can be done using a single dry gas mixture without the need for cooling or monitoring F CO2. This test can be used to identify and stu "5 y patients with EIA without the requirement for an exercise challenge or the need for elaborate gas conditioning and monitoring equipment.
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PREDICTION OF LATE ASTHMATIC RESPONSES TO INHALED ALLERGEN. L-P Boulet. M.D.. F.E. Hargreave. M.D. and 3. Dolovich, M.D., Hamilton, Ontario, Canada. Relationships between skin and airway responses to allergen were examined in 15 allergic asthmatic patients. Allergen inhalation tests elicited an isolated early asthmatic response (EAR) in 10 and dual asthmatic response (DAR ) in 9. Ragweed RAST, in those challenged with ragweed, was lower in all EAR patients than any DAR patients except 1 whose serum yielded a negative IgE RAST. The allergens inhaled were used in serial dilutions in skin tests. Ten minute "heal (W) and 8 hour late cutaneous response (LCAR) mean diameters were measured. EAR subjects differed modestly from DAR subjects in relationships between W and LCAR: in the EAR a significantly larger wheal diameter group, (p < 0.01) was required for LCAR to ensue, however there was considerable overlap. Once LCAR developed, there was no difference between the EAR and DAR groups in the magnitude of the LCAR. There was a trend (not significant) towards a higher injected antigen concentration needed to provoke a LCAR in the EAR group. In conclusion, the occurrence of a DAR from inhaled antigen is suggested by (i) a high IgE RAST result with the antigen, (ii) W 5 mm or less which proceeds to LCAR and (iii) LCAR from a low concentration of antigen in the skin tests. The observed correspondence between the tendency to late skin and late airway responses is evidence of a common immunologic basis.
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CLINICAL/BIOCHEMICAL ASSESSMENT OF ACQUIRED CTINH DEFICIENCY. A.L. Sheffer, M.D., J. Melamed, M.D., D.T. kearon, M.D., and K.F. Austen, M.D., Harvard Med. Sc h ., B oston, MA Clinical and biochemical appraisals of acquired CTINH deficiency and angioedema (AME) have been performed in 4 male and 2 female patients, ranging in age from 7 to 57, over periods ranging from 3 mos. to 6 yrs. Two had lymphatic leukemia; 1 presented initially with ANE and was found to have a lymphoma 21 mos. later. Three have had no clinically definable underlying disorder. Presenting manifestation(s) included laryngeal edema (LE) in 3, cutaneous ANE in 5, and incapacitating GI colic in 1. One required chronic prophylaxis with stanozolol for LE, 1 received periodic therapy for GI colic, and 4 have not experienced recurThe complement abnormalities rence of attacks. in all 6 included levels of CH50 which ranged from 43 to 144 U/ml (normals, 150-250); CTINH, 1.2-11.9 mg/dl (normals, 16 to 34); Clq, 5-43.8 mg/dl (normals, 35-56); and C4 protein, O-16.4 mg/dl (normals, 28-83) with means of 82.5, 3.8, 21.7 and 15.9, respectively. The mean Clq for a group of hereditary angioedema patients was 4CJ* 16 mg/dl (n = 61. Fractional catabolic rates of CTINH turnover performed in 3 patients with acquired CTINH deficiency was 5.3X, as compared to 3.5% in the hereditary form, and 2.5% in norThus, the defect in the acquired mal subjects. form is catabolic, and biosynthetic in the can hereditary form. Acquired CTINH deficiency be a paraneoplastic disorder that may precede clinical recognition of the underlying disease. The diagnosis is confirmed by reduced Clq in association with CiINH and C4 reductions.
75
USEFULNESS OF ir50 IN THE INTERPRETATION OF THE METHACHOLINE INHALATION CHALLENGE TEST. W. E. Imber, M.D., C. E. Reed, M.D., R. E. Hyatt, M.D. P. W. Welsh, B.A., Eliseo Anorve-Lopez, M.D., K. Offord, M.S., B. .I. Dain, B.A., and E. Frigas, M.D. Rochester, Minnesota A decrease in FEVl of 20% or greater after methacholine challenge is a widely used criterion of asthma. The forced expiratory flow at 50% Of vital capacity ($50) is a sensitive, effortindependent measure of air flow. Over a g-year period, 473 patients at the Mayo Clinic with normal baseline spirometry received a methacholine inhalation challenge test. In this population, 102 (22%) had a decrease in FEVl of less than 20% concomitantly with a decrease in i50 of greater than 20%. Among this subgroup, 41 (50%) were diagnosed as asthmatic (Group A) at the initial visit or on follow-up 1-11 years later, 21 (25%) were diagnosed as nonasthmatic (Group B) and 20 (25%) had a clinical presentation suggestive of asthma but not sufficient at the time of examination or follow-up to warrant the diagnosis (Group C). A significant correlation between AFEVl and At50 after methacholine challenge was found (0.89, p < 0.0001). These results indicate that measurement of V50 during methacholine challenge when used in conjunction with the history and physical examination may serve to identify a group of asthmatics which otherwise would not have been detected by the FEVl criterion alone. In addition, a borderline group (C) is described in which more intensive follow-up may be indicated in order to detect the evolution of asthmatic symptoms not present on initial examination.
74
SIMPLIFIED ISOCAPNIC HYPERVENTILATION TEST. Y.Y. Phillips, M.D., J.J. Jaeger, Ph.D., R.R. RosenB.L. Laube, B.A., and P.S. Norman, thal, M.D., Washington, D.C. and Baltimore, Maryland a, We wish to describe a greatly simplified system which can provide significant levels of respiratory heat exchange (RHE) in asthmatics. A single dry gas mixture consisting of 4.9% CO2 in air is delivered through a rotameter to a target balloon at any desired flow rate. When multiple measurements (n=llO) were made on 19 normal subjects at voluntary ventilatory rates (VE) of 40 to 105 l/min we observed the average FetC02 to be 0.0585 + 0.0012. Next, a group of 7 patients with exercise induced asthma (EIA) were challenged with a standard exercise protocol ventilating ad libitum from a source of dry air at room temperature.. RHE was computed and on another day the same VE was required of them using the simplified isocapnic hyperventilation (IH) scheme. The average RHE for the exercise challenge was -1.5 + 0.4 Kcal/min and for the IH challenge -1.5 5 0.5 Kcal/min (p>O.20 by paired student t The maximum fall in FEVl after the exertest). cise challenge was 29 + 5% and after IH 29 2 10% The maximum falls in SGaw were 62 + (PbO.90). 14% and 73 + 9% after exercise and IH respectively (p>O.lO). We conclude that a simplified RHE challenge can be done using a single dry gas mixture without the need for cooling or monitoring F CO2. This test can be used to identify and stu "5 y patients with EIA without the requirement for an exercise challenge or the need for elaborate gas conditioning and monitoring equipment.
76
PREDICTION OF LATE ASTHMATIC RESPONSES TO INHALED ALLERGEN. L-P Boulet. M.D.. F.E. Hargreave. M.D. and 3. Dolovich, M.D., Hamilton, Ontario, Canada. Relationships between skin and airway responses to allergen were examined in 15 allergic asthmatic patients. Allergen inhalation tests elicited an isolated early asthmatic response (EAR) in 10 and dual asthmatic response (DAR ) in 9. Ragweed RAST, in those challenged with ragweed, was lower in all EAR patients than any DAR patients except 1 whose serum yielded a negative IgE RAST. The allergens inhaled were used in serial dilutions in skin tests. Ten minute "heal (W) and 8 hour late cutaneous response (LCAR) mean diameters were measured. EAR subjects differed modestly from DAR subjects in relationships between W and LCAR: in the EAR a significantly larger wheal diameter group, (p < 0.01) was required for LCAR to ensue, however there was considerable overlap. Once LCAR developed, there was no difference between the EAR and DAR groups in the magnitude of the LCAR. There was a trend (not significant) towards a higher injected antigen concentration needed to provoke a LCAR in the EAR group. In conclusion, the occurrence of a DAR from inhaled antigen is suggested by (i) a high IgE RAST result with the antigen, (ii) W 5 mm or less which proceeds to LCAR and (iii) LCAR from a low concentration of antigen in the skin tests. The observed correspondence between the tendency to late skin and late airway responses is evidence of a common immunologic basis.
107