Late asthmatic response to allergen challenge (LAR), its clinical feature and pharmacological modulation.
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Biomedical subjects
Publications and source records attributed to Z Pelikan.
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One hundred sixty-four patients with allergic rhinitis (104 patients with positive late nasal responses (LNRs) and 60 patients with negative nasal responses to allergen challenge), correlating with history and skin tests, were randomly selected for this study. Nasal challenges were repeated and supplemented by cytologic examination of the nasal secretions (NSs). The cytologic examination of NS was also performed during 164 control challenges with phosphate-buffered saline. The positive LNR was accompanied by significant changes in the count of neutrophils in 84% of the cases (increase immediately before and decrease during appearance of LNR, with increase again during resolving of late nasal response), of eosinophils in 58% (increase immediately before and decrease during appearance of LNR), of epithelial cells in 73% (increase followed by decrease, running parallel with LNR), of goblet cells in 63% (increase followed by decrease), of basophils in 8%, and of lymphocytes in 6% (both of these cells demonstrated a slight increase during LNR) in the NS. No significant changes in the count of other types of cells in the NS during most of the LNR cases were recorded. Most cases of negative response were not accompanied by significant changes in the count of individual cell types. No significant changes in the count of any cell type in the NS were recorded in any patient during the phosphate-buffered saline-control challenges. The cytologic examination of NS, accompanying the nasal challenge with allergen, appears therefore to be a valuable supplementary diagnostic parameter for the LNR and a promising model for further immunologic and clinical studies of the LNR.
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A routine diagnostic procedure, the food-focused history, intracutaneous tests with food extracts, and ingestion challenge with selected foods in combination with rhinomanometry were performed in 142 patients suffering from perennial allergic rhinitis. Forty-one of the 47 patients with a "positive food allergy history" developed 65 (90%) positive nasal responses during 72 food ingestion challenges. Of the 95 patients with an "unknown food allergy history," 54 developed 68 (50%) positive nasal responses during 132 food ingestion challenges. The following responses were recorded: 29 isolated immediate (within three hours), 38 isolated late (six to 24 hours), 42 dual late (immediate + late), 11 isolated delayed (28 to 52 hours), and 13 dual delayed (immediate + delayed). It can be concluded that the involvement of foods in allergic rhinitis is more frequent than is usually expected. The definite confirmation of the role of a certain food in these patients should be provided by the food ingestion challenge demonstrating one of the clinical types of nasal response. The mechanisms underlying the nasal response to foods are not yet fully clarified. The involvement of different types of hypersensitivity in the individual types of nasal response cannot be excluded.
In 102 randomly selected patients with allergic rhinitis caused by immediate hypersensitivity, nasal provocation tests (NPTs) with allergens were evaluated by means of rhinomanometry, and cytologic examination of the nasal secretions (NSs) was performed. The cells in NS of 117 positive immediate nasal responses (INRs) and in 68 negative INRs, correlating with history and skin tests, and in 102 control challenges with phosphate-buffered saline were stained by modified May-Grünwald-Giemsa, toluidine blue, and Hansel's method. The positive INR was accompanied by significant changes in the count of eosinophils (increase followed by decrease) in 67% of neutrophils (decrease followed by increase) in 40%, goblet cells (increase followed by decrease) in 41%, and basophils (decrease) in 13% of the NSs. No significant changes in the count of other types of cells in the NSs were recorded during most of the cases of INR. No significant changes in the count of individual cell types in NSs were found during most cases of negative INR. During the phosphate-buffered saline control challenges, the individual cell types appeared irregularly, and no significant changes in their count were recorded in any patient. The cytologic examination of NS, evoked by allergen, appears therefore to be a valuable supplementary diagnostic parameter for nasal allergy. The repeated counting of eosinophils in NS, before and after allergen challenge, appears to be the best way to discriminate between positive and negative nasal responses, since the eosinophils demonstrated significant changes in their count during 67% of the positive and only 11% of the negative INRs.
This study deals with comparative investigation of the protective effects of disodium cromoglycate (DSCG, Lomudal, Intal) and beclomethasone dipropionate aerosol (BDA, Aldecin, Becotide, Beclovent) on 103 immediate asthmatic responses (IARs) to allergen challenge recorded in 103 patients with an allergic bronchial asthma. Disodium cromoglycate demonstrated highly significant protective effects on the IAR in patients investigated (P less than .01). The protective effects of BDA on the IAR were found to be non-significant (P greater than .01). It is suggested that DSCG should be the first choice in controlling allergic bronchial asthma when the immediate asthmatic response to allergen plays the predominant role.
The protective effects of disodium cromoglycate (DSCG; Lomudal, Intal) and beclomethasone dipropionate (BDA; Aldecin, Becotide, Beclovent) on the late asthmatic response to allergen challenge (LAR) were investigated in 61 patients with allergic bronchial asthma. The 61 patients developed a total of 83 late asthmatic responses, 35 isolated late responses (ILAR), and 48 dual late responses (DLAR), which is a combination of an immediate response (IDLAR) and a late response (LDLAR). Disodium cromoglycate demonstrated significant protective effects on the LAR (P less than .01), however, the LDLAR as part of the DLAR was decreased by DSCG to a slightly higher degree than the ILAR. The BDA also showed significant protective effects on the LAR (P less than .01), but the ILAR was protected by BDA to a slightly higher degree than the LDLAR as part of the DLAR. The immediate asthmatic response as part of the DLAR was prevented by DSCG significantly (P less than .01) while the BDA was ineffective (P greater than .05). It can be concluded that both DSCG and BDA demonstrated significant effects on the LAR. It is suggested that DSCG should be used as a drug of the first choice to control bronchial asthma with an allergy component where the LAR plays a role. The BDA should be added temporarily at the beginning of the treatment of patients in whom the isolated late asthmatic response plays the predominant role, or of patients in whom the DSCG does not provide full control of the LAR during a certain period, eg, during the peak of the pollen season.(ABSTRACT TRUNCATED AT 250 WORDS)
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A total of 143 food ingestion challenges were carried out in 107 patients suffering from bronchial asthma of a perennial type. In the group of 21 patients with "positive or highly suggestive food history" related to their bronchial complaints, 21 food challenges were performed. In the group of 86 patients with "unknown food history," 122 ingestion challenges with foods causing a positive skin response were performed. Fifteen of the 21 patients with "positive food history" developed 15 (71%) bronchus-obstructive responses to foods ingested, while 45 of the 86 patients with "unknown food history" developed 68 (56%) bronchial responses to the food ingestion challenge. Twenty-three isolated immediate (within 2 hours), 11 isolated late (4 to 24 hours), 34 dual late (a combination of an immediate and a late), 6 isolated delayed (28 to 56 hours), and 9 dual delayed (a combination of an immediate and delayed) bronchus-obstructive responses were recorded. No significant correlation of the individual types of bronchial response to food ingested with other in vivo and in vitro diagnostic parameters were found. Although the exact pathogenetic and immunologic mechanisms underlying the particular types of bronchial response to foods are not yet fully clarified, the involvement of different types of hypersensitivity cannot be excluded. It could be concluded that the involvement of foods in bronchial asthma is more frequent than is usually expected. The diagnostic value of the food ingestion challenge seems to be superior to that of other diagnostic parameters. The definite confirmation of the role of a certain food, in patients with bronchial asthma, should therefore be provided by the food ingestion challenge demonstrating one of the clinical types of bronchus-obstructive response.
The views on the pathogenetic and immunologic mechanisms presumably involved in the late asthmatic response (LAR) vary. Some investigators suggested the role of late hypersensitivity and IgG antibodies. Other authors assumed the role of the immediate hypersensitivity, mediated by IgE antibodies, with involvement of mast cells (and/or basophils). Another group of investigators assume that non-specific hyperreactivity could contribute to the development of the LAR. Finally, other investigators assumed that various combinations and modifications of established types of hypersensitivity mechanisms could be involved in the LAR. In the literature, there is a large quantity of various information, results, and hypotheses concerning the late asthmatic response which are, however, often controversial. The authors attempted to summarize the hypotheses and facts concerning LAR and to compare them with the results of their study in order to better understand LAR.
Of the 251 patients with bronchial asthma, 61 (24%) developed 83 late asthmatic (bronchus-obstructive) responses (LAR) to the bronchial challenge with allergen (BP). The LAR began within 6 to 12 hours, reached its maximum within 4 to 8 hours, and resolved within 24 to 26 hours after the allergen challenge. All LARs were highly significant in comparison with the control test (P less than .01). The LAR was observed either as an isolated late response (ILAR) in 35 cases (10%) or as a dual late response (DAR) in 48 cases (14%), being a combination of an immediate (IDAR) and a late response (LDAR). The LAR demonstrated six basic patterns. The association of LAR with other diagnostic parameters was as follows: positive disease history in 49 LAR cases (59%); positive late skin response (LSR) in 51 LAR cases (61%); increased total serum IgE in 17 LAR (20%); positive specific IgE in the serum in 24 LAR cases (29%); increased serum concentration of IgG in 55 LAR cases (66%), of IgM in 41 LAR cases (49%), of IgA in one LAR case (1%); increased serum concentration of IgG1 in seven LARs (8%), of IgG3 in 21 LARs (25%), of IgG4 in 43 LARs (52%), the serum concentration of IgG2 increased in two LARs, while it decreased in 45 LARs (54%); increased blood eosinophilia in 42 LAR cases (51%) and blood leukocytosis in 29 LAR cases (35%); increased body temperature in 15 LAR cases (18%); appearance of late bronchial complaints during 83 LAR cases (100%), and of general malaise complaints during 67 LAR cases (81%).(ABSTRACT TRUNCATED AT 250 WORDS)
One hundred and three bronchial asthma patients with a suspected allergic component developed 133 positive immediate asthmatic (bronchus-obstructive) responses (IARs) to bronchial challenge with allergen (BP). The onset of IAR was within 10 minutes, the maximum within 45 minutes, and the resolution of the response within 120 minutes after the challenge. All IARs were highly significant in comparison with the control test (p less than .01). The association of IAR with other diagnostic parameters was the following: positive disease history in 82 IAR cases (= 62%); positive immediate skin response in 91 IAR cases (= 68%); increased total serum IgE in 54 IAR cases (= 41%); positive specific IgE in the serum in 59 IAR cases (= 44%); increased serum concentration of IgG in 36 IAR cases (= 27%), of IgM in 17 (= 13%), and of IgA in 3 IAR cases (= 2%); increased blood eosinophilia in 36 (= 27%) and blood leukocytosis in 19 IAR cases (= 14%); increased bronchial reactivity to histamine in 74 of 103 patients with IAR (= 72%); body temperature increased during nine IAR cases (= 7%); and 131 IAR cases (= 98%) were accompanied by bronchial and 62 (= 47%) by general malaise complaints. The IAR showed a very good reproducibility and significant dose-response relationship (P less than .01). In conclusion, the IAR is an important diagnostic parameter for the allergic component due to immediate hypersensitivity in the bronchial tree. The correlation of other diagnostic parameters with IAR was not satisfactory. They should therefore be regarded as diagnostic supplement only.(ABSTRACT TRUNCATED AT 250 WORDS)
The protective effects of disodium cromoglycate (DSCG) and beclomethasone dipropionate (BDA) on the "delayed nasal response" to allergen challenge (DNR) were investigated in 37 patients with allergic rhinitis. These thirty-seven patients, from a group of 268, developed 43 "delayed nasal responses" (DNR), 16 cases of "isolated delayed responses" (IDNR) and 27 cases of "dual delayed responses" (DDNR), where the delayed response (DLDNR) was preceded by an immediate response (INR). BDA demonstrated significant protective effects on the DNR in both its modifications; however, to a higher degree in the case of the IDNR. DSCG significantly decreased only the INR, being a part of the DDNR, while in the case of the DNR in both its modifications, DSCG was completely ineffective. It is suggested that BDA should be the drug of first choice in allergic rhinitis patients demonstrating the DNR. When immediate responses to the same or other allergens are also present, DSCG should be added at the beginning of the treatment for a temporary period of a few months.
In 162 patients with allergic rhinitis due to immediate hypersensitivity, nasal provocation tests (NPT) were supplemented by recording of the eosinophils in the nasal secretions (NS). Nasal secretion specimens were obtained before and repeatedly after allergen challenge and stained by a modified Hansel's method. The 188 positive immediate nasal responses (INR) that correlated with positive skin tests and history and 92 negative INR that correlated with negative skin tests and history were studied. Several different types of eosinophil response to allergen challenge were observed. Eosinophilia was found in the NS in 84% of patients with positive INR but in only 49% of patients with negative INR. The eosinophil count before allergen challenge was low in 79.5% of positive INR and in 76.5% of negative INR, whereas it was high in 20.5% of positive INR and in 23.5% of negative INR. The positive INR were accompanied by significant changes (p less than 0.01) in the eosinophil count between before and after allergen challenge in 74% and the negative INR in only 19% of the cases. These changes appeared within 30 min after allergen challenge. This study shows that only a single count of eosinophils in the NS is not a suitable indicator of nasal allergy. The recording of eosinophils in the NS can be considered as a useful supplementary diagnostic parameter for the possible involvement of immediate hypersensitivity in the nasal mucosa if (1) the eosinophil count is related to a certain allergen and (2) the eosinophils are recorded before and repeatedly up to 60 min after allergen challenge.