MEDLINE Abstracts: Immunotherapy in Asthma
MEDLINE Abstracts: Immunotherapy in Asthma
What's new concerning immunotherapy in asthma? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape Allergy & Clinical Immunology.
Jain V, Kitagaki K, Kline J
Clin Exp Allergy. 2003;33:1330-1335
Atopic asthma is a highly prevalent and serious health problem for which no therapy currently offers the hope of a cure. Preindustrialized and rural populations appear relatively protected from the asthma epidemic; the hygiene hypothesis ascribes this protection to the effects of microbes and microbial products. An important immunostimulant component of microbes is DNA; bacterial DNA contains sequence motifs centred on the CpG dinucleotide, which are suppressed in mammalian DNA. Oligonucleotides containing these motifs (CpG ODN), like bacterial DNA, promote Th1 and regulatory-type immune responses. Using CpG ODN, we and others have demonstrated in murine studies that CpG ODN are effective in preventing the development of atopic airways disease. Moreover, when administered in conjunction with experimental allergen, they promote the reversal of established eosinophilic inflammation. These data suggest that CpG ODN may be a novel therapeutic tool for the treatment of atopic asthma.
Chiang DJ, Ye YL, Chen WL, Lee YL, Hsu NY, Chiang BL
Am J Respir Crit Care Med. 2003;168:575-580
Asthma is an allergic disease that is characterized by the imbalance between Th1 and Th2 cells and by the predominant Th2-type immune response. In this study, we investigated the application of dendritic cell (DCs)-based immunotherapy in modulating the immune response of allergic diseases. DCs incubated with ovalbumin (OVA), OVA plus ribavirin, OVA plus CpG-oligodeoxynucleotides (ODN 1826), or OVA plus non-CpG-ODN (ODN 1745) for 48 hours were injected intravenously into four corresponding groups of BALB/c mice. All of the mice were then immunized with OVA intraperitoneally 7 days later to establish an animal model of asthma. Serum levels of OVA antibody, airway hyperresponsiveness, cell composition, and cytokine levels in the bronchoalveolar lavage fluid, and cytokine profiles of spleen cells were analyzed. The data showed that ribavirin and ODN 1826 increased interleukin-12 synthesis and inhibited interleukin-10 production. ODN 1826 could also enhance the expression of B7.1, B7.2, major histocompatibility complex I, and major histocompatibility complex II molecules. Furthermore, the DCs modulated by ribavirin and ODN 1826 could downregulate the Th2-type immune response in vivo and could alleviate airway inflammation. This study elucidated the effect of ribavirin and CpG-ODN on DCs and demonstrated that in vitro modulated DCs might be a potential therapeutic approach for asthma.
Katial RK
Immunol Allergy Clin North Am. 2003;23:483-499
The ubiquitous existence of cockroaches and the large-scale domestic infestation seen in inner cities make cockroach proteins a significant indoor allergen and a risk factor for asthma among inner-city residents. Studies have shown that early exposure to high levels of allergen may lead to the development of asthma in individuals with a genetic predisposition to asthma. Although field trials at cockroach abatement do not yield promising results, integrated pest management still remains the best control strategy. In highly susceptible or symptomatic patients, allergen-specific immunotherapy may be beneficial, although data are limited. As molecular techniques improve and recombinant allergens are developed, a more novel form of T-cell-specific immunotherapy may prove to be efficacious without the anaphylactic side effects seen with traditional allergy vaccines.
Sehra S, Pynaert G, Tournoy K, et al
J Immunol. 2003;171:2080-2089
Besides IgE, the Ab isotype that gives rise to sensitization and allergic asthma, the immune response to common inhalant allergens also includes IgG. Increased serum titers of allergen-specific IgG, induced spontaneously or by allergen vaccination, have been implicated in protection against asthma. To verify the interference of topical IgG with the allergen-triggered eosinophilic airway inflammation that underlies asthma, sensitized mice were treated by intranasal instillation of specific IgG, followed by allergen challenge. This treatment strongly reduced eosinophilic inflammation and goblet cell metaplasia, and increased Th1 reactivity and IFN-gamma levels in bronchoalveolar lavage fluid. In contrast, inflammatory responses were unaffected in IFN-gamma-deficient mice or when applying F(ab')(2). Although dependent on specific allergen-IgG interaction, inflammation triggered by bystander allergens was similarly repressed. Perseverance of inflammation repression, apparent after secondary allergen challenge, and increased allergen capture by alveolar macrophages further characterized the consequences of topical IgG application. These results assign a novel protective function to anti-allergen IgG namely at the local level interference with the inflammatory cascade, resulting in repression of allergic inflammation through an FcgammaR- and IFN-gamma-dependent mechanism. Furthermore, these results provide a basis for topical immunotherapy of asthma by direct delivery of anti-allergen IgG to the airways.
Langley SJ, Goldthorpe S, Craven M, Morris J, Woodcock A, Custovic A
J Allergy Clin Immunol. 2003;112:362-368
Background: Exposure to high levels of allergens in sensitized asthmatic patients causes worsening of pulmonary function in experimental studies. Chronic exposure to lower, naturally occurring levels of allergens might increase the severity of asthma.
Objective: We sought to study the associations between sensitization and exposure to common indoor allergens (dust mite, cat, and dog) in the home on pulmonary function, exhaled nitric oxide (eNO), and airway reactivity in asthmatic patients.
Methods: Dust samples were collected from the living room carpet and mattress of 311 subject's homes, and Der p 1, Fel d 1, and Can f 1 concentrations were measured by using ELISAs. Spirometry, nonspecific bronchial reactivity, and eNO were measured.
Results: Subjects both sensitized and exposed to high levels of sensitizing allergen had significantly lower forced expiratory volume in 1 second (FEV1) percent predicted values (mean, 83.7% vs 89.3%; mean difference, 5.6%; 95% CI, 0.6%-10.6%; P = .03), higher eNO values (geometric mean [GM], 12.8 vs 8.7 ppb; GM ratio, 0.7; 95% CI, 0.5-0.8; P = .001), and more severe airways reactivity (PD(20) GM, 0.25 vs 0.73 mg; GM ratio, 2.9; 95% CI, 1.6-5.0; P < .001) compared with subjects not sensitized and exposed. No significant effect of the interaction between sensitization and exposure was found for FEV1 percent predicted and eNO values. However, there was a significant effect of the interaction between sensitization and exposure to any allergen (P = .05) and between sensitization and exposure to cat allergen (P = .04) for nonspecific bronchial reactivity.
Conclusion: Asthmatic subjects who are exposed in their homes to allergens to which they are sensitized have a more severe form of the disease.
Perry T, Matsui E, Merriman B, Duong T, Eggleston P
J Allergy Clin Immunol. 2003;112:346-352
Background: Rat allergen has proved to be an important cause of IgE-mediated hypersensitivity in the occupational setting. The prevalence and significance of rat allergen in homes has not been studied.
Objective: The purpose of this study was to determine the prevalence of rat allergen in the homes of inner-city children with asthma and to examine the relationship between rat allergen exposure, sensitization, and asthma morbidity.
Methods: We developed a new monoclonal-based ELISA to determine the prevalence of rat allergen in dust samples from inner-city homes of the National Cooperative Inner-City Asthma Study population. Home characteristics were evaluated to detect variables that were associated with the presence of rat allergen. Data were also analyzed to assess the relationship between the presence of rat allergen, sensitization, and asthma morbidity.
Results: Thirty-three percent of inner-city homes had detectable rat allergen (Rat n 1). The presence of rat allergen was associated with reported rat and mouse infestation, as well as evidence of mouse infestation on home inspection. Twenty-one percent of the participants were sensitized to rat allergen; however, sensitization was not more common when rat allergen was found in the home. The number of hospitalizations, unscheduled medical visits, and days with slowed activity because of asthma were significantly increased in those individuals who were both sensitized and exposed to rat allergen.
Conclusions: Rat allergen sensitization and exposure are associated with increased asthma morbidity in inner-city children.
Tella R, Bartra J, San Miguel M, et al
Allergol Immunopathol. 2003;31:221-225
Background: Specific immunotherapy (SIT) is the only treatment that interferes with the basic pathophysiological mechanisms of allergic disease and is widely used in the management of clinically significant respiratory IgE-mediated diseases. Nevertheless, until recently, information on the influence of SIT on the development of new allergic sensitisations has been scant.
Methods: One hundred consecutive patients (45 males and 55 females, aged 6 to 69 years) with respiratory allergic diseases and attending the allergy unit of a general hospital were selected. All had been diagnosed by clinical history and skin prick tests of allergic rhinitis and/or asthma, were monosensitised (71 to Dermatophagoides spp, 22 to Parietaria judaica pollen and 7 to grass pollen) and had been followed up as outpatients between 1990 and 1998. Sixty-six patients had been treated with conventional SIT for at least 3 years, while thirty-four followed only environmental measures and drug treatment. Family atopy status (first-degree relatives), smoking, family pets (cat and/or dog), rhinitis, and/or asthma symptom score and inhalant skin prick tests to the same aeroallergens were compared between baseline and after 3 to 5 years of treatment.
Results: No statistically-significant differences in the development of new sensitisations were observed between the two groups (36.4% of SIT-treated patients versus 38.2% in control group, RR = 0.97, CI 95%: 0.72-1.3). Smoking, family atopy history, and pets did not appear to be risk factors for the development of neosensitisations (P < .05). Nevertheless, SIT-treated patients presented a better clinical score than the control group, with improvements of 89.4% and 61.8%, respectively (P = .007).
Conclusions: Three-year SIT did not protect against development of new sensitisations in monosensitised allergic rhinitis or asthma. Smoking, family atopy history, and pets were not associated with development of new sensitisations. Clinical score improved significantly in the SIT-treated group compared with drug-treated patients.
Olea europaea Pollen Allergens Significantly Reduces Specific Bronchial and Skin Test Reactivity in Sensitized Patients After One Year of Treatment
Guerra F, Daza JC, Almeda E
J Investig Allergol Clin Immunol. 2003;13:108-117
Clinical manifestations after the inhalation of Olea europaea pollen are very frequent in Spain. Forty-five patients with a clinical history of asthma and sensitivity to O europaea pollen were included in a randomized trial to evaluate the safety and the clinical efficacy of immunotherapy with a new chemically modified extract (depigmented and glutaraldehyde-polymerized) of Olea europaea. The study was conducted following good clinical practices and appropriate consent forms were signed. Patients were divided into three groups of 15 individuals: Group A received a maximum concentration of 44 micrograms/ml of the depigmented, polymerized allergen extract (equivalent to 100 HEPL of the native unmodified extract). Group B received 10 times less; Group C did not receive any specific immunotherapy. Any adverse event was recorded to assess safety. Efficacy was evaluated by measuring the amount of allergen needed to elicit a positive response in specific bronchial challenges before and after 12 months of immunotherapy. The treatment schedule consisted of an incremental phase of five injections and a maintenance dosage of 0.5 ml per month. Each patient received a total of 14 injections during this period. No moderate or serious adverse events related to immunotherapy were recorded. At the beginning of the study, no significant differences were observed between the three groups in specific bronchial hyperreactivity (P > .05). A significant difference (P < .05) was obtained after 12 months. Patients in Group A needed four times more native unmodified allergen than Group C to elicit the same degree of bronchoconstriction. The analysis of the individual groups before and after 12 months of treatment showed that patients in Groups B and C did not improve. Patients in Group A showed a significant improvement (P < .05) in specific bronchial hyperreactivity, and at the end of the study needed 5.5 times more native unmodified allergen to obtain the same degree of bronchial response as in the beginning. Depigmented and glutaraldehyde-polymerized vaccines of Olea europaea pollen are very safe for treating patients with asthma and clinical sensitivity to allergens of this pollen. The clinical efficacy of this new allergen vaccine seems to be dose-dependent as shown by specific bronchial challenges as well as by symptom and medication scores. These modified extracts induce protection against unmodified native allergens.
Polosa R, Li Gotti F, Mangano G, Mastruzzo C, Pistorio MP, Crimi N
Clin Exp Allergy. 2003;33:873-881
Bronchial hyper-responsiveness (BHR) is documented in a proportion of non-asthmatic individuals with allergic rhinitis (NAAR) and reflects inflammatory events in the lower airways. Natural exposure to allergens is known to modulate BHR and the level of airway inflammation in asthma, but less consistently in NAAR. Specific immunotherapy (SIT) attenuates symptoms possibly by reducing BHR and airway inflammation. The influence of natural exposure to Parietaria pollen on BHR and sputum cell counts of NAAR was investigated and the effect of Parietaria SIT examined. Thirty NAAR, monosensitized to Parietaria judaica, participated in a randomized, double-blind, placebo-controlled, parallel group study of the effects of a Parietaria pollen vaccine on symptoms/medication score, BHR to inhaled methacholine and adenosine 5'-monophosphate (AMP), and cell counts in the sputum collected out of and during the pollen seasons for 36 months. Seasonal variation in BHR to inhaled methacholine and AMP and changes in sputum cell counts were documented. Changes were consistent for AMP, but not methacholine, and invariably associated with modifications in sputum eosinophils and epithelial cells. The clinical efficacy of Parietaria SIT was associated with a decline in the seasonal deterioration of BHR to AMP, whereas no significant effect was observed on BHR to methacholine or sputum cell differentials. Between-groups comparison of the seasonal changes in PC15 methacholine values and sputum cell differentials calculated as the AUC were not statistically significant, whereas a significant difference in PC15 AMP was demonstrated throughout the study (P = .029), the median (inter-quartile range) AUC values being 2478.5 (1153.3-3600.0) and 1545.5 (755.3-1797.9) for the SIT- and placebo-treated group, respectively. Bronchial airways of NAAR exhibit features of active inflammation that deteriorate during natural allergen exposure, particularly with regard to BHR to AMP. The clinical efficacy of Parietaria SIT was exclusively associated with attenuation in seasonal worsening of PC15 AMP, suggesting that AMP may be useful in monitoring changes in allergic inflammation of the airways.
Jain VV, Businga TR, Kitagaki K, George CL, O'Shaughnessy PT, Kline JN
Am J Physiol Lung Cell Mol Physiol. 2003 Jul 11 [Epub ahead of print]
Murine models of acute atopic asthma may be inadequate to study the effects of recurrent exposure to inhaled allergens, such as the epithelial changes seen in asthmatic patients. We developed a murine model in which chronic airway inflammation is maintained by repeated allergen (ovalbumin, OVA) inhalation; using this model, we examined the response to mucosal administration of CpG DNA (oligonucleotides) and specific antigen immunotherapy. Mice repeatedly exposed to OVA developed significantly greater airway hyperresponsiveness and goblet cell hyperplasia, but not airway eosinophilia, compared with those exposed only twice. CpG-based immunotherapy significantly reversed both acute and chronic markers of inflammation as well as airway hyperresponsiveness. We further examined the effect of mucosal immunotherapy on the response to a second, unrelated, antigen. Mice sensitized to both OVA and schistosome eggs, challenged with inhaled OVA, and then treated with OVA-directed immunotherapy demonstrated significant reduction of airway hyperresponsiveness and a moderate reduction in eosinophilia, after inhalation challenge with schistosome egg antigens. In this model, immunotherapy treatment reduced bronchoalveolar lavage (BAL) levels of Th2 cytokines (interleukin [IL]-4, IL-5, IL-13, and IL-10) without changing BAL IFN-gamma. Antigen-recall responses of splenocytes from these mice demonstrated an antigen-specific (OVA) enhanced release of IL-10 from splenocytes of treated mice. These results suggest that CpG DNA may provide the basis for a novel form of immunotherapy of allergic asthma. Both antigen-specific and, to a lesser extent, antigen-nonspecific, responses to mucosal administration of CpG DNA are seen.
Pajno GB, Peroni DG, Barberio G, Boner AL
Chem Immunol Allergy. 2003;82:77-88
Sublingual immunotherapy (SLIT) is the local route of administration of allergen extracts investigated in several controlled clinical trials. In a number of countries, particularly Italy, France, and Spain, this has become common in office practice. At variance with subcutaneous immunotherapy, the knowledge of mechanisms of action of SLIT is still at the beginning: some studies, in animal models, provided interesting information: the dendritic cells of oral mucosa act as efficient antigen-presenting cells and produce IL-12, which directs the immune response towards a Th1 profile away from IgE-Th2 profile. Its clinical efficacy (improvement of symptoms and reduction of drug intake) for both asthma and rhinitis has been assessed in detail for the most common allergens: house dust mites, grass pollen, Parietaria, birch pollen, and olive tree. SLIT requires further evaluation concerning the treatment of the extrinsic form of atopic dermatitis. The induction of immunologic tolerance rather than immunoreactivity should be worth pursuing due to the immunologic pathway involved in the pathophysiology of atopic dermatitis. The safety profile of SLIT, derived from the clinical trials and postmarketing surveillance studies, turned out to be satisfactory in adults and children. SLIT represents an important step towards an efficacious and safe treatment of patients with allergic respiratory diseases; nevertheless, further studies are necessary to establish it as a viable alternative to subcutaneous immunotherapy.
Reyes Moreno A, Castrejon Vazquez MI, Miranda Feria AJ
Rev Alerg Mex. 2003;50:8-12
Background: Allergic asthma is the reversible chronic inflammatory process in the airways, secondary to exaggerate reply to the allergens exposition, its treatment includes: avoiding the exposure to allergens, pharmacology therapy, and specific immunotherapy with allergens (ITA), which is based on the growing dosages of the extract allergenic. The objectives are to modify the immune response and to improve the allergic disease. ITA can fail due to causes attributable to the patient, vaccine-inherent causes, and/or factors related to the allergic disease.
Objective: To determine the main causes of specific immunotherapy with allergens' failure in our hospital.
Materials and Methods: In the present study, 126 records of patients with allergic asthma treated in the extern consultation service of the clinical immunology and allergy department of the CMN 20 de Noviembre, ISSSTE, were reviewed from January 1996 to December 2001.
Results: It was found that specific immunotherapy with allergens failed in 32 (23%) patients. Main causes of failure were: 1) withdrawal in the vaccine application in 19 (59%) patients; 2) high serum levels of IgE. The co-morbidities that contribute to poor responses to the treatment were: obesity, gastroesophageal reflux and chronic rhinosinusitis.
Conclusions: Specific immunotherapy with allergens is an alternative method of allergic asthma treatment, which has been approved by national and international medical consensus. Main causes of failure in our hospital are the abandon of treatment and high serum levels of IgE, as well as the existence of other conditions.
Olea europaea Quantified in Mass Units. Evaluation of the Safety and Efficacy After One Year of Treatment
Gonzalez P, Florido F, Saenz de San Pedro B, de la Torre F, Rico P, Martin S
J Investig Allergol Clin Immunol. 2002;12:263-271
Sensitization to olive pollen is a frequent cause of rhinoconjunctivitis (RC) and bronchial asthma (BA) in the region of Jaen (southern Spain), where this allergen reaches atmospheric levels of almost 7000 grains/m during pollen season (May and June) and produces high morbidity. Specific immunotherapy (SIT) has proven very efficient in allergic RC and BA caused by grass pollen. Considering the availability of a biologically standardized extract of Olea europaea, with its major allergen quantified in mass units, we decided to investigate SIT with this extract in a group of rhinitic and/or asthmatic patients monosensitized to olive. We studied tolerance, safety, and efficacy by comparison of the active group (subjected to SIT) with a control group that did not receive SIT. A hyposensitizing dose of Olea europaea extract was administered preseasonally, establishing a maintenance dose 3.8 times higher than those administered in conventional treatments. Eighty-three percent of the patients reached the proposed maximal dose of 75 BU, equivalent to 45 micrograms Ole e 1, with a rate of 0.8% of systemic reactions. A significant decrease in cutaneous (P < .001) and bronchial (P < .001) reactivity was observed in the active group, but not in the control group. Also, a decrease in specific IgE and an increase in IgG1 and IgG4 were found in the group of patients treated with SIT. Regarding clinical evolution, the active group, but not the control group, experienced a clear statistically significant improvement both in nasal (P < .05) and bronchial (P < .05) symptoms, in addition to a significant decrease in the consumption of antihistamines (P < .05) and beta2-agonists (P < .01). In conclusion, SIT with olive extract proved to be safe and efficacious for the treatment of asthma and rhinitis caused by this allergen.
What's new concerning immunotherapy in asthma? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape Allergy & Clinical Immunology.
Jain V, Kitagaki K, Kline J
Clin Exp Allergy. 2003;33:1330-1335
Atopic asthma is a highly prevalent and serious health problem for which no therapy currently offers the hope of a cure. Preindustrialized and rural populations appear relatively protected from the asthma epidemic; the hygiene hypothesis ascribes this protection to the effects of microbes and microbial products. An important immunostimulant component of microbes is DNA; bacterial DNA contains sequence motifs centred on the CpG dinucleotide, which are suppressed in mammalian DNA. Oligonucleotides containing these motifs (CpG ODN), like bacterial DNA, promote Th1 and regulatory-type immune responses. Using CpG ODN, we and others have demonstrated in murine studies that CpG ODN are effective in preventing the development of atopic airways disease. Moreover, when administered in conjunction with experimental allergen, they promote the reversal of established eosinophilic inflammation. These data suggest that CpG ODN may be a novel therapeutic tool for the treatment of atopic asthma.
Chiang DJ, Ye YL, Chen WL, Lee YL, Hsu NY, Chiang BL
Am J Respir Crit Care Med. 2003;168:575-580
Asthma is an allergic disease that is characterized by the imbalance between Th1 and Th2 cells and by the predominant Th2-type immune response. In this study, we investigated the application of dendritic cell (DCs)-based immunotherapy in modulating the immune response of allergic diseases. DCs incubated with ovalbumin (OVA), OVA plus ribavirin, OVA plus CpG-oligodeoxynucleotides (ODN 1826), or OVA plus non-CpG-ODN (ODN 1745) for 48 hours were injected intravenously into four corresponding groups of BALB/c mice. All of the mice were then immunized with OVA intraperitoneally 7 days later to establish an animal model of asthma. Serum levels of OVA antibody, airway hyperresponsiveness, cell composition, and cytokine levels in the bronchoalveolar lavage fluid, and cytokine profiles of spleen cells were analyzed. The data showed that ribavirin and ODN 1826 increased interleukin-12 synthesis and inhibited interleukin-10 production. ODN 1826 could also enhance the expression of B7.1, B7.2, major histocompatibility complex I, and major histocompatibility complex II molecules. Furthermore, the DCs modulated by ribavirin and ODN 1826 could downregulate the Th2-type immune response in vivo and could alleviate airway inflammation. This study elucidated the effect of ribavirin and CpG-ODN on DCs and demonstrated that in vitro modulated DCs might be a potential therapeutic approach for asthma.
Katial RK
Immunol Allergy Clin North Am. 2003;23:483-499
The ubiquitous existence of cockroaches and the large-scale domestic infestation seen in inner cities make cockroach proteins a significant indoor allergen and a risk factor for asthma among inner-city residents. Studies have shown that early exposure to high levels of allergen may lead to the development of asthma in individuals with a genetic predisposition to asthma. Although field trials at cockroach abatement do not yield promising results, integrated pest management still remains the best control strategy. In highly susceptible or symptomatic patients, allergen-specific immunotherapy may be beneficial, although data are limited. As molecular techniques improve and recombinant allergens are developed, a more novel form of T-cell-specific immunotherapy may prove to be efficacious without the anaphylactic side effects seen with traditional allergy vaccines.
Sehra S, Pynaert G, Tournoy K, et al
J Immunol. 2003;171:2080-2089
Besides IgE, the Ab isotype that gives rise to sensitization and allergic asthma, the immune response to common inhalant allergens also includes IgG. Increased serum titers of allergen-specific IgG, induced spontaneously or by allergen vaccination, have been implicated in protection against asthma. To verify the interference of topical IgG with the allergen-triggered eosinophilic airway inflammation that underlies asthma, sensitized mice were treated by intranasal instillation of specific IgG, followed by allergen challenge. This treatment strongly reduced eosinophilic inflammation and goblet cell metaplasia, and increased Th1 reactivity and IFN-gamma levels in bronchoalveolar lavage fluid. In contrast, inflammatory responses were unaffected in IFN-gamma-deficient mice or when applying F(ab')(2). Although dependent on specific allergen-IgG interaction, inflammation triggered by bystander allergens was similarly repressed. Perseverance of inflammation repression, apparent after secondary allergen challenge, and increased allergen capture by alveolar macrophages further characterized the consequences of topical IgG application. These results assign a novel protective function to anti-allergen IgG namely at the local level interference with the inflammatory cascade, resulting in repression of allergic inflammation through an FcgammaR- and IFN-gamma-dependent mechanism. Furthermore, these results provide a basis for topical immunotherapy of asthma by direct delivery of anti-allergen IgG to the airways.
Langley SJ, Goldthorpe S, Craven M, Morris J, Woodcock A, Custovic A
J Allergy Clin Immunol. 2003;112:362-368
Background: Exposure to high levels of allergens in sensitized asthmatic patients causes worsening of pulmonary function in experimental studies. Chronic exposure to lower, naturally occurring levels of allergens might increase the severity of asthma.
Objective: We sought to study the associations between sensitization and exposure to common indoor allergens (dust mite, cat, and dog) in the home on pulmonary function, exhaled nitric oxide (eNO), and airway reactivity in asthmatic patients.
Methods: Dust samples were collected from the living room carpet and mattress of 311 subject's homes, and Der p 1, Fel d 1, and Can f 1 concentrations were measured by using ELISAs. Spirometry, nonspecific bronchial reactivity, and eNO were measured.
Results: Subjects both sensitized and exposed to high levels of sensitizing allergen had significantly lower forced expiratory volume in 1 second (FEV1) percent predicted values (mean, 83.7% vs 89.3%; mean difference, 5.6%; 95% CI, 0.6%-10.6%; P = .03), higher eNO values (geometric mean [GM], 12.8 vs 8.7 ppb; GM ratio, 0.7; 95% CI, 0.5-0.8; P = .001), and more severe airways reactivity (PD(20) GM, 0.25 vs 0.73 mg; GM ratio, 2.9; 95% CI, 1.6-5.0; P < .001) compared with subjects not sensitized and exposed. No significant effect of the interaction between sensitization and exposure was found for FEV1 percent predicted and eNO values. However, there was a significant effect of the interaction between sensitization and exposure to any allergen (P = .05) and between sensitization and exposure to cat allergen (P = .04) for nonspecific bronchial reactivity.
Conclusion: Asthmatic subjects who are exposed in their homes to allergens to which they are sensitized have a more severe form of the disease.
Perry T, Matsui E, Merriman B, Duong T, Eggleston P
J Allergy Clin Immunol. 2003;112:346-352
Background: Rat allergen has proved to be an important cause of IgE-mediated hypersensitivity in the occupational setting. The prevalence and significance of rat allergen in homes has not been studied.
Objective: The purpose of this study was to determine the prevalence of rat allergen in the homes of inner-city children with asthma and to examine the relationship between rat allergen exposure, sensitization, and asthma morbidity.
Methods: We developed a new monoclonal-based ELISA to determine the prevalence of rat allergen in dust samples from inner-city homes of the National Cooperative Inner-City Asthma Study population. Home characteristics were evaluated to detect variables that were associated with the presence of rat allergen. Data were also analyzed to assess the relationship between the presence of rat allergen, sensitization, and asthma morbidity.
Results: Thirty-three percent of inner-city homes had detectable rat allergen (Rat n 1). The presence of rat allergen was associated with reported rat and mouse infestation, as well as evidence of mouse infestation on home inspection. Twenty-one percent of the participants were sensitized to rat allergen; however, sensitization was not more common when rat allergen was found in the home. The number of hospitalizations, unscheduled medical visits, and days with slowed activity because of asthma were significantly increased in those individuals who were both sensitized and exposed to rat allergen.
Conclusions: Rat allergen sensitization and exposure are associated with increased asthma morbidity in inner-city children.
Tella R, Bartra J, San Miguel M, et al
Allergol Immunopathol. 2003;31:221-225
Background: Specific immunotherapy (SIT) is the only treatment that interferes with the basic pathophysiological mechanisms of allergic disease and is widely used in the management of clinically significant respiratory IgE-mediated diseases. Nevertheless, until recently, information on the influence of SIT on the development of new allergic sensitisations has been scant.
Methods: One hundred consecutive patients (45 males and 55 females, aged 6 to 69 years) with respiratory allergic diseases and attending the allergy unit of a general hospital were selected. All had been diagnosed by clinical history and skin prick tests of allergic rhinitis and/or asthma, were monosensitised (71 to Dermatophagoides spp, 22 to Parietaria judaica pollen and 7 to grass pollen) and had been followed up as outpatients between 1990 and 1998. Sixty-six patients had been treated with conventional SIT for at least 3 years, while thirty-four followed only environmental measures and drug treatment. Family atopy status (first-degree relatives), smoking, family pets (cat and/or dog), rhinitis, and/or asthma symptom score and inhalant skin prick tests to the same aeroallergens were compared between baseline and after 3 to 5 years of treatment.
Results: No statistically-significant differences in the development of new sensitisations were observed between the two groups (36.4% of SIT-treated patients versus 38.2% in control group, RR = 0.97, CI 95%: 0.72-1.3). Smoking, family atopy history, and pets did not appear to be risk factors for the development of neosensitisations (P < .05). Nevertheless, SIT-treated patients presented a better clinical score than the control group, with improvements of 89.4% and 61.8%, respectively (P = .007).
Conclusions: Three-year SIT did not protect against development of new sensitisations in monosensitised allergic rhinitis or asthma. Smoking, family atopy history, and pets were not associated with development of new sensitisations. Clinical score improved significantly in the SIT-treated group compared with drug-treated patients.
Olea europaea Pollen Allergens Significantly Reduces Specific Bronchial and Skin Test Reactivity in Sensitized Patients After One Year of Treatment
Guerra F, Daza JC, Almeda E
J Investig Allergol Clin Immunol. 2003;13:108-117
Clinical manifestations after the inhalation of Olea europaea pollen are very frequent in Spain. Forty-five patients with a clinical history of asthma and sensitivity to O europaea pollen were included in a randomized trial to evaluate the safety and the clinical efficacy of immunotherapy with a new chemically modified extract (depigmented and glutaraldehyde-polymerized) of Olea europaea. The study was conducted following good clinical practices and appropriate consent forms were signed. Patients were divided into three groups of 15 individuals: Group A received a maximum concentration of 44 micrograms/ml of the depigmented, polymerized allergen extract (equivalent to 100 HEPL of the native unmodified extract). Group B received 10 times less; Group C did not receive any specific immunotherapy. Any adverse event was recorded to assess safety. Efficacy was evaluated by measuring the amount of allergen needed to elicit a positive response in specific bronchial challenges before and after 12 months of immunotherapy. The treatment schedule consisted of an incremental phase of five injections and a maintenance dosage of 0.5 ml per month. Each patient received a total of 14 injections during this period. No moderate or serious adverse events related to immunotherapy were recorded. At the beginning of the study, no significant differences were observed between the three groups in specific bronchial hyperreactivity (P > .05). A significant difference (P < .05) was obtained after 12 months. Patients in Group A needed four times more native unmodified allergen than Group C to elicit the same degree of bronchoconstriction. The analysis of the individual groups before and after 12 months of treatment showed that patients in Groups B and C did not improve. Patients in Group A showed a significant improvement (P < .05) in specific bronchial hyperreactivity, and at the end of the study needed 5.5 times more native unmodified allergen to obtain the same degree of bronchial response as in the beginning. Depigmented and glutaraldehyde-polymerized vaccines of Olea europaea pollen are very safe for treating patients with asthma and clinical sensitivity to allergens of this pollen. The clinical efficacy of this new allergen vaccine seems to be dose-dependent as shown by specific bronchial challenges as well as by symptom and medication scores. These modified extracts induce protection against unmodified native allergens.
Polosa R, Li Gotti F, Mangano G, Mastruzzo C, Pistorio MP, Crimi N
Clin Exp Allergy. 2003;33:873-881
Bronchial hyper-responsiveness (BHR) is documented in a proportion of non-asthmatic individuals with allergic rhinitis (NAAR) and reflects inflammatory events in the lower airways. Natural exposure to allergens is known to modulate BHR and the level of airway inflammation in asthma, but less consistently in NAAR. Specific immunotherapy (SIT) attenuates symptoms possibly by reducing BHR and airway inflammation. The influence of natural exposure to Parietaria pollen on BHR and sputum cell counts of NAAR was investigated and the effect of Parietaria SIT examined. Thirty NAAR, monosensitized to Parietaria judaica, participated in a randomized, double-blind, placebo-controlled, parallel group study of the effects of a Parietaria pollen vaccine on symptoms/medication score, BHR to inhaled methacholine and adenosine 5'-monophosphate (AMP), and cell counts in the sputum collected out of and during the pollen seasons for 36 months. Seasonal variation in BHR to inhaled methacholine and AMP and changes in sputum cell counts were documented. Changes were consistent for AMP, but not methacholine, and invariably associated with modifications in sputum eosinophils and epithelial cells. The clinical efficacy of Parietaria SIT was associated with a decline in the seasonal deterioration of BHR to AMP, whereas no significant effect was observed on BHR to methacholine or sputum cell differentials. Between-groups comparison of the seasonal changes in PC15 methacholine values and sputum cell differentials calculated as the AUC were not statistically significant, whereas a significant difference in PC15 AMP was demonstrated throughout the study (P = .029), the median (inter-quartile range) AUC values being 2478.5 (1153.3-3600.0) and 1545.5 (755.3-1797.9) for the SIT- and placebo-treated group, respectively. Bronchial airways of NAAR exhibit features of active inflammation that deteriorate during natural allergen exposure, particularly with regard to BHR to AMP. The clinical efficacy of Parietaria SIT was exclusively associated with attenuation in seasonal worsening of PC15 AMP, suggesting that AMP may be useful in monitoring changes in allergic inflammation of the airways.
Jain VV, Businga TR, Kitagaki K, George CL, O'Shaughnessy PT, Kline JN
Am J Physiol Lung Cell Mol Physiol. 2003 Jul 11 [Epub ahead of print]
Murine models of acute atopic asthma may be inadequate to study the effects of recurrent exposure to inhaled allergens, such as the epithelial changes seen in asthmatic patients. We developed a murine model in which chronic airway inflammation is maintained by repeated allergen (ovalbumin, OVA) inhalation; using this model, we examined the response to mucosal administration of CpG DNA (oligonucleotides) and specific antigen immunotherapy. Mice repeatedly exposed to OVA developed significantly greater airway hyperresponsiveness and goblet cell hyperplasia, but not airway eosinophilia, compared with those exposed only twice. CpG-based immunotherapy significantly reversed both acute and chronic markers of inflammation as well as airway hyperresponsiveness. We further examined the effect of mucosal immunotherapy on the response to a second, unrelated, antigen. Mice sensitized to both OVA and schistosome eggs, challenged with inhaled OVA, and then treated with OVA-directed immunotherapy demonstrated significant reduction of airway hyperresponsiveness and a moderate reduction in eosinophilia, after inhalation challenge with schistosome egg antigens. In this model, immunotherapy treatment reduced bronchoalveolar lavage (BAL) levels of Th2 cytokines (interleukin [IL]-4, IL-5, IL-13, and IL-10) without changing BAL IFN-gamma. Antigen-recall responses of splenocytes from these mice demonstrated an antigen-specific (OVA) enhanced release of IL-10 from splenocytes of treated mice. These results suggest that CpG DNA may provide the basis for a novel form of immunotherapy of allergic asthma. Both antigen-specific and, to a lesser extent, antigen-nonspecific, responses to mucosal administration of CpG DNA are seen.
Pajno GB, Peroni DG, Barberio G, Boner AL
Chem Immunol Allergy. 2003;82:77-88
Sublingual immunotherapy (SLIT) is the local route of administration of allergen extracts investigated in several controlled clinical trials. In a number of countries, particularly Italy, France, and Spain, this has become common in office practice. At variance with subcutaneous immunotherapy, the knowledge of mechanisms of action of SLIT is still at the beginning: some studies, in animal models, provided interesting information: the dendritic cells of oral mucosa act as efficient antigen-presenting cells and produce IL-12, which directs the immune response towards a Th1 profile away from IgE-Th2 profile. Its clinical efficacy (improvement of symptoms and reduction of drug intake) for both asthma and rhinitis has been assessed in detail for the most common allergens: house dust mites, grass pollen, Parietaria, birch pollen, and olive tree. SLIT requires further evaluation concerning the treatment of the extrinsic form of atopic dermatitis. The induction of immunologic tolerance rather than immunoreactivity should be worth pursuing due to the immunologic pathway involved in the pathophysiology of atopic dermatitis. The safety profile of SLIT, derived from the clinical trials and postmarketing surveillance studies, turned out to be satisfactory in adults and children. SLIT represents an important step towards an efficacious and safe treatment of patients with allergic respiratory diseases; nevertheless, further studies are necessary to establish it as a viable alternative to subcutaneous immunotherapy.
Reyes Moreno A, Castrejon Vazquez MI, Miranda Feria AJ
Rev Alerg Mex. 2003;50:8-12
Background: Allergic asthma is the reversible chronic inflammatory process in the airways, secondary to exaggerate reply to the allergens exposition, its treatment includes: avoiding the exposure to allergens, pharmacology therapy, and specific immunotherapy with allergens (ITA), which is based on the growing dosages of the extract allergenic. The objectives are to modify the immune response and to improve the allergic disease. ITA can fail due to causes attributable to the patient, vaccine-inherent causes, and/or factors related to the allergic disease.
Objective: To determine the main causes of specific immunotherapy with allergens' failure in our hospital.
Materials and Methods: In the present study, 126 records of patients with allergic asthma treated in the extern consultation service of the clinical immunology and allergy department of the CMN 20 de Noviembre, ISSSTE, were reviewed from January 1996 to December 2001.
Results: It was found that specific immunotherapy with allergens failed in 32 (23%) patients. Main causes of failure were: 1) withdrawal in the vaccine application in 19 (59%) patients; 2) high serum levels of IgE. The co-morbidities that contribute to poor responses to the treatment were: obesity, gastroesophageal reflux and chronic rhinosinusitis.
Conclusions: Specific immunotherapy with allergens is an alternative method of allergic asthma treatment, which has been approved by national and international medical consensus. Main causes of failure in our hospital are the abandon of treatment and high serum levels of IgE, as well as the existence of other conditions.
Olea europaea Quantified in Mass Units. Evaluation of the Safety and Efficacy After One Year of Treatment
Gonzalez P, Florido F, Saenz de San Pedro B, de la Torre F, Rico P, Martin S
J Investig Allergol Clin Immunol. 2002;12:263-271
Sensitization to olive pollen is a frequent cause of rhinoconjunctivitis (RC) and bronchial asthma (BA) in the region of Jaen (southern Spain), where this allergen reaches atmospheric levels of almost 7000 grains/m during pollen season (May and June) and produces high morbidity. Specific immunotherapy (SIT) has proven very efficient in allergic RC and BA caused by grass pollen. Considering the availability of a biologically standardized extract of Olea europaea, with its major allergen quantified in mass units, we decided to investigate SIT with this extract in a group of rhinitic and/or asthmatic patients monosensitized to olive. We studied tolerance, safety, and efficacy by comparison of the active group (subjected to SIT) with a control group that did not receive SIT. A hyposensitizing dose of Olea europaea extract was administered preseasonally, establishing a maintenance dose 3.8 times higher than those administered in conventional treatments. Eighty-three percent of the patients reached the proposed maximal dose of 75 BU, equivalent to 45 micrograms Ole e 1, with a rate of 0.8% of systemic reactions. A significant decrease in cutaneous (P < .001) and bronchial (P < .001) reactivity was observed in the active group, but not in the control group. Also, a decrease in specific IgE and an increase in IgG1 and IgG4 were found in the group of patients treated with SIT. Regarding clinical evolution, the active group, but not the control group, experienced a clear statistically significant improvement both in nasal (P < .05) and bronchial (P < .05) symptoms, in addition to a significant decrease in the consumption of antihistamines (P < .05) and beta2-agonists (P < .01). In conclusion, SIT with olive extract proved to be safe and efficacious for the treatment of asthma and rhinitis caused by this allergen.
