Nebulized fluticasone propionate, a viable alternative to systemic route in the management of childhood moderate asthma attack: A double-blind, double-dummy study.

BACKGROUND: In this study, we compared the clinical and immunological efficacy of nebulized corticosteroid (CS) to systemic route during treatment of moderate asthma attack in children. METHODS: In this randomized, placebo-controlled, double-blind, double-dummy, prospective study, 81 children aged 12 months to 16 years experiencing asthma attack randomized into two treatment groups to receive, either; nebulized fluticasone propionate (n = 39, 2000 mcg/day) or oral methylprednisolone (n = 41, 1 mg/kg/day). Pulmonary index scores (PIS) were assessed at admission and at 1st, 4th, 8th, 12th, 24th, 48th hours, as well as, on day 7 and peak expiratory flow (PEF) at baseline and at the 7th day. Daily symptom and medication scores were recorded for all subjects. Immunological studies included phytohemagglutinin induced peripheral blood mononuclear cells culture supernatant for cytokine responses and CD4(+) CD25(+) FOXP3(+) T regulatory cell (T reg) percentage at baseline and day 7. RESULTS: The changes in PIS and PEF were similar in both treatment groups, with a significant improvement in both values at the 7th day, when compared to baseline. In both groups, significant reductions in symptom and medication scores were observed during the treatment period with no significant difference between the groups. At day 7 of intervention, phytohemagglutinin induced IL-4 level was significantly decreased only in the nebulized group compared to baseline (p = 0.01). Evaluation of cytokine responses by means of fold increase (stimulated (S)/unstimulated (US) ratio) revealed a significant reduction in IL-4, IL-5 and IL-17 only in nebulized group (p = 0.01, 0.01, 0.02; respectively). The fold increase value of IL-5 was significantly lower at 7th day in nebulized group when compared to systemic one (p = 0.02). At 7th day, although in both treatment groups the percentage of T reg cells was suppressed, it remained significantly higher in the nebule one when compared to systemic route (p = 0.04). CONCLUSION: In the management of moderate acute asthma attack, nebulized CS (2000 mcg daily) was found to be as effective as systemic route with regard to clinical improvement. In addition, immunological parameters were more in favor of nebulized route which may imply a salutary effect of local CS usage.

JAGN1 Deficient Severe Congenital Neutropenia: Two Cases from the Same Family.

Recently autosomal recessively inherited mutations in the gene encoding Jagunal homolog 1 (JAGN1) was described as a novel disease-causing gene of severe congenital neutropenia (SCN) JAGN1-mutant neutrophils were characterized by abnormality in endoplasmic reticulum structure, absence of granules, abnormal N-glycosylation of proteins and susceptibility to apoptosis. These findings imply the role of JAGN1 in neutrophil survival. Here, we report two siblings with a homozygous mutation in JAGN1 gene, exhibiting multisystemic involvement.

Long-Term Effect of Sublingual and Subcutaneous Immunotherapy in Dust Mite-Allergic Children With Asthma/Rhinitis: A 3-Year Prospective Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Specific allergen immunotherapy is the only treatment modality that might change the natural course of allergic diseases in childhood. We sought to prospectively compare the long-term clinical and immunological effects of sublingual (SLIT) and subcutaneous (SCIT) immunotherapy compared with pharmacotherapy alone. METHODS: In this single-center, prospective randomized controlled trial, 48 children with mild persistent asthma with/without rhinitis, monosensitized to house dust mites (HDMs) were followed for 3 years. At baseline and years 1 and 3 of follow-up, patients were evaluated and compared for total rhinitis (TRSS) and asthma (TASS) symptom scores, total symptom scores (TSS), total medication scores (TMS), safety profiles, skin-nasal-bronchial reactivity, and immunological parameters. RESULTS: A significant reduction was observed in TASS for both HDM-SCIT and HDM-SLIT at year 3 of treatment compared with baseline and controls (P<.05 for both), with significant improvement in rhinitis symptoms for both groups compared with controls (P=.01 for both). TSS decreased significantly in both HDM-SCIT and HDM-SLIT at year 3 compared with baseline (P=.007 and P=.04, respectively) and controls (P<.01 for both). A significant reduction in TMS was observed in HDM-SCIT and HDM-SLIT compared with baseline and controls (P=.01 in all cases), with a reduction in skin reactivity to HDM (P<.05). Finally, a significant increase in allergen specific IgG4 was observed in the SCIT group at year 3 compared with baseline, the SLIT group, and controls (P<.001 in all cases). CONCLUSIONS: HDM-sensitized asthmatic children treated for at least 3 years with either SCIT or SLIT showed sustained clinical improvement.

Alteration in humoral immunity is common among family members of patients with common variable immunodeficiency.

BACKGROUND: The prevalence of primary immunodeficiency (PID) in the relatives of patients with common variable immunodeficiency (CVID) and IgA deficiency is high. Allergic disorders have been recorded in patients with humoral immunodeficiency. We aimed to determine the frequency of humoral immunodeficiency and atopy in the relatives of patients with CVID. METHODS: The study population comprised 20 CVID patients and their relatives. All relatives were screened using a questionnaire covering demographic characteristics, warning signs of PID (adults and children), and core questions on asthma, rhinitis, and eczema from the International Study of Asthma and Allergies in Childhood (ISAAC). We also recorded absolute neutrophil and lymphocyte counts, serum immunoglobulin levels, pulmonary function values, and skin prick test results. RESULTS: The study sample comprised 20 patients with CVID (15 males, 5 females; mean (SD] age, 16.4 (9] years) and 63 first-degree relatives (18 mothers, 16 fathers, 16 sisters, 10 brothers, and 3 offspring). The rate of parental consanguinity was 75%. Of 17 family members with positive PID warning signs, 6 had concomitant hypogammaglobulinemia (3 low IgM levels, 2 selective IgA deficiency, and 1 partial IgA deficiency). The ISAAC questionnaire revealed allergic rhinitis in 3 mothers, asthma in 2 fathers, and 1 sibling. Skin prick testing revealed sensitization to aeroallergens in 31.6% of cases in addition to 1 parent and 1 sibling. CONCLUSIONS: Almost half of the 20 families with a CVID patient had at least 1 additional member with hypogammaglobulinemia, leading us to recommend routine screening for relatives of CVID patients.

Vitamin D as an adjunct to subcutaneous allergen immunotherapy in asthmatic children sensitized to house dust mite.

BACKGROUND: We aimed to investigate the efficacy, safety, and T regulatory cell response of vitamin D as an adjunct to allergen-specific immunotherapy (IT). METHODS: Fifty children with asthma and receiving pharmacotherapy were randomized into three groups as: subcutaneous IT (SCIT) along with vitamin D supplementation (650 U/day; n: 17), SCIT alone (n: 15), and pharmacotherapy alone (n: 18). All patients were evaluated at baseline, 6th and 12th months for scorings of symptoms and medication, skin prick testing, total IgE, specific IgE, and Der p 1-specific IgG4. In addition, D. pteronyssinus-induced CD4(+) CD25(+) FOXP3(+) T regulatory cell percentage, intracellular Foxp3 expression, and peripheral blood mononuclear cell IL-10 and TGF-ß responses were assessed. RESULTS: In the SCIT + vitamin D and SCIT alone groups, total asthma symptom score (TASS), total symptom score (TSS), and total medication scores (TMS) were significantly lower than pharmacotherapy group at the end of 1 year. While the comparison of delta values (Δ 6th and Δ 12th month - baseline) of those scores revealed no significant differences between the two IT groups, TASS at the 6th month was lower in the SCIT + vitamin D group compared with others. There was a significant and positive trend in the levels of Der p 1-specific IgG4 in both IT groups throughout the study period. Whereas the levels of Der p 1-induced IL-10 and TGF-ß were similar between IT groups, the mean fluorescence intensity of Foxp3 was highest in the SCIT + vitamin D group compared with others at the 12th month. The rate of discontinuation of inhaled corticosteroid (ICS) was 6/17 in SCIT + vitamin D, 3/15 in SCIT, and 0/18 in the pharmacotherapy group (P = 0.02). CONCLUSION: Both SCIT groups fared better than pharmacotherapy alone at the end of 1 year. Although the clinical and immunologic outcomes were mostly similar between the two IT groups, some favorable outcomes of vitamin D warrant further investigation in more selected populations with varying doses as adjunct to IT.

Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial.

BACKGROUND: In children, the clinical efficacy and immunological mechanisms of sublingual immunotherapy (SLIT) compared with subcutaneous immunotherapy (SCIT) is still to be elucidated. OBJECTIVES: To compare SLIT, SCIT and pharmacotherapy in relation to clinical efficacy and immunological mechanisms that govern its effect in asthmatic/rhinitis children who were sensitized to house dust mite (HDM). METHODS: In this single centre, prospective, randomized, controlled, open labelled, three parallel group trial, 48 patients mono-sensitized to HDM were randomized to receive either SLIT (n=16), SCIT (n=16) or pharmacotherapy alone (n=16). Symptom, medication and visual analogue score (VAS) were collected and bronchial-nasal hyper-reactivity, skin prick tests, total-specific IgE were performed at baseline and 12 months after treatment. In addition, peripheral blood mononuclear cells were cultured with recombinant Der p 1 and Bet v 1 extracts and allergen-specific IL-4, IL-5, IL-13, IFN-gamma, IL-10, and TGF-beta secretions were measured. RESULTS: SLIT and SCIT demonstrated a significant reduction of total rhinitis and asthma symptom score, total medication score, VAS and skin reactivity to HDM (P<0.05) when compared with pharmacotherapy. A significant reduction of serum-specific HDM-IgE in SCIT and SLIT were observed. Moreover, titrated nasal provocative dose significantly increased in both immunotherapy groups when compared with the pharmacotherapy group. No adverse effects were reported in SLIT, while two patients demonstrated serious adverse events in SCIT. After 1 year of treatment, Der p 1-driven IL-10 significantly increased in SLIT compared with pharmacotherapy, whereas Bet v 1-driven TGF-beta (negative control) increased significantly in SLIT only. No changes were observed for Th1-Th2 cytokines. CONCLUSION: Both SLIT and SCIT demonstrated clinical improvement compared with pharmacotherapy in asthma/rhinitis children sensitized to HDM.

Prevalence of immediate hypersensitivity reactions to cow's milk in infants based on skin prick test and questionnaire.

OBJECTIVE: Cow's milk (CM) hypersensitivity is one of the most frequent hypersensitivities in infants. The objective of our study was to investigate the prevalence of immediate hypersensitivity to CM based on skin prick test results and to evaluate associated allergic conditions ascertained by questionnaire in infants living in Istanbul. METHODS: All infants born between June 2001 and May 2002 were recalled to the hospital according to their dates of birth, and 1015 infants aged between 8-18 months were included in the study. An interview was conducted with each mother and a questionnaire requesting data on cow's milk hypersensitivity and other allergic diseases was completed during this interview. A cow's milk skin prick test (SPT) was applied to all infants. An open CM challenge test was then carried out on infants with a positive SPT to CM. RESULTS: Among the 1015 infants who underwent SPT, six (0.59 %) demonstrated immediate hyper-sensitivity to the CM allergen and three (0.29 %) developed a positive response to the CM challenge test. The results of the questionnaire revealed that 112 (11.0 %) of the infants had family history of allergic diseases, 96 infants (9.5 %) had a positive history of recurrent wheezing, and 166 (16.4 %) had a history of skin rash resembling atopic dermatitis. CONCLUSIONS: Our results suggest that CM hyper-sensitivity, with its low prevalence, might not be a serious health concern in Turkish infants.

Clinical and immunologic features of pediatric patients with common variable immunodeficiency and respiratory complications.

BACKGROUND: Common variable immunodeficiency (CVID) is the term used to describe a heterogeneous group of B-cell deficiency syndromes characterized by hypogammaglobulinemia, impaired antibody production, and recurrent bacterial infections. OBJECTIVES: To determine the clinical manifestations and perform an immunological analysis of pediatric CVID patients suffering from respiratory complications. METHODS: The records of 10 patients with CVID who were followed up from 1992 to 2005 (6 males and 4 females) with a median (interquartile range) age of 13.9 (10.4-19.4) years were reviewed. All patients met the standard criteria set for CVID. RESULTS: Median total serum levels of immunoglobulin (Ig) G, IgM, and IgA in mg/dL were 383.5 (239.2-574.5), 32.5 (17.0-117.0), and 12.5 (5.0-30.7), respectively. Median age at the onset of symptoms, at CVID diagnosis, and on starting intravenous Ig therapy was 4.0 (0.8-6.2), 9.4 (6.7-11.3), and 9.1 (7.0-11.6) years, respectively. Associated disorders were recurrent infections (100%), bronchiectasis (90%), and growth failure (80%), whereas malabsorption, malignant neoplasm, inflammatory bowel disease, and autoimmune disorders were less common. All bronchiectatic patients had a low percentage of B cells, with an average of 4% (range, 1%-7%). The characteristic computed tomography finding in patients with CVID was a multilobar pattern. Malignant neoplasm developed an average of 11.5 (range, 6.5-20.2) years after the diagnosis of CVID was made. CONCLUSION: Recurrent respiratory infection should be evaluated to rule out CVID. Early diagnosis and intravenous Ig replacement therapy may reduce the frequency of respiratory infection. Low levels of serum Ig and percentage of B lymphocytes at diagnosis are important parameters for identifying patients at risk of structural lung damage.

Prevalence of egg sensitization in Turkish infants based on skin prick test.

AIM: Egg allergy is one of the most frequent allergies in infants. The aim of this study was to determine the frequency of sensitization to egg in infants based on skin prick test results and to evaluate associated allergic conditions by questionnaire. METHODS: All infants born between June 2001 and May 2002 were recalled to the hospital according to their dates of birth, and 1015 infants aged between 8-18 months were included in the study. An interview was conducted with each mother and a questionnaire requesting data on food allergy and other allergic diseases was completed during this interview. An egg skin prick test (whole egg) was applied to all infants. RESULTS: Positive skin prick test results were recorded in 19 infants (1.87 %). There was no difference between the prick test-positive and -negative groups with respect to any of the demographic characteristics investigated (gender, age, birth weight, egg consumption, age of introduction of egg and other solids, breastfeeding). No significant association was demonstrated between sensitization to egg and family history of allergy. Moreover, there was no association between sensitization to egg and occurrence of atopic dermatitis, recurrent wheezing, gastrointestinal symptoms and doctor diagnosis of asthma. CONCLUSION: The prevalence of egg sensitization based on skin prick test results has been found as 1.87 % among Turkish infants in Istanbul. However, no significant relationship was found between allergic sensitization to egg and occurrence of allergic diseases in this study population.

Prevalence of egg sensitization in Turkish infants based on skin prick test

Aim: Egg allergy is one of the most frequent allergies in infants. The aim of this study was to determine the frequency of sensitization to egg in infants based on skin prick test results and to evaluate associated allergic conditions by questionnaire. Methods: All infants born between June 2001 and May 2002 were recalled to the hospital according to their dates of birth, and 1015 infants aged between 8-18 months were included in the study. An interview was conducted with each mother and a questionnaire requesting data on food allergy and other allergic diseases was completed during this interview. An egg skin prick test (whole egg) was applied to all infants. Results: Positive skin prick test results were recorded in 19 infants (1.87 %). There was no difference between the prick test-positive and -negative groups with respect to any of the demographic characteristics investigated (gender, age, birth weight, egg consumption, age of introduction of egg and other solids, breastfeeding). No significant association was demonstrated between sensitization to egg and family history of allergy. Moreover, there was no association between sensitization to egg and occurrence of atopic dermatitis, recurrent wheezing, gastrointestinal symptoms and doctor diagnosis of asthma. Conclusion: The prevalence of egg sensitization based on skin prick test results has been found as 1.87 % among Turkish infants in Istanbul. However, no significant relationship was found between allergic sensitization to egg and occurrence of allergic diseases in this study population

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CD4+ T cells from mice with intestinal immediate-type hypersensitivity induce airway hyperreactivity.

BACKGROUND: A subset of food-allergic patients does not only respond clinically with symptoms in the gastro-intestinal tract but also with asthmatic reactions. OBJECTIVE: The aim of this study was to analyse whether CD4+ T cells from mice with intestinal immediate-hypersensitivity reactions to food allergen are involved in the development of experimental asthma. METHODS: BALB/c mice were intraperitoneally sensitized to ovalbumin (OVA), followed by repeated intra-gastric (i.g.) OVA challenges. Control animals were either sham-sensitized or sham-challenged with phosphate-buffered saline (PBS). Duodenum, jejunum, ileum and colon were histologically examined. CD4+ T cells from mesenteric lymph nodes were transferred from various donor groups into recipient mice that received either OVA or PBS aerosol challenges. Recipients were analysed by measurements of lung function using head-out body-plethysmography and examination of broncho-alveolar lavage and lung histology. RESULTS: The highest levels of OVA-specific IgE antibody levels were detected in OVA-sensitized and OVA-challenged mice. Throughout the lower intestinal tract, a marked infiltration with eosinophils was observed, and goblet cell numbers as well as goblet cell area were significantly increased. The villus/crypt ratio was decreased compared with controls. The transfer of CD4+ T cells from mesenteric lymph nodes of OVA-sensitized and OVA-challenged mice triggered airway hyperreactivity and eosinophilic airway inflammation in recipients aerosol challenged with OVA, but not with PBS. CONCLUSION: We conclude that CD4+ T cells from mesenteric lymph nodes of mice with allergen-induced immediate-type hypersensitivity reactions in the gut are able to transfer the phenotype of experimental asthma.

Highlights in cellular and molecular mechanisms of allergic diseases. XXVth Congress of the European Academy of Allergology and Clinical Immunology in Vienna.

This year, the annual congress of the European Academy of Allergology and Clinical Immunology was held on 10-14 June in Vienna. More than 6,000 delegates, practicing bench or bedside work or both, gathered from over 50 countries throughout the world. Health professionals, basic scientists and fellows in training could choose between a variety of activities in plenary, main, educational and workshop sessions, highlights of the past year, pros and cons, and oral abstract and poster sessions, and met with experts. A total of 1,713 abstracts, 31 symposia, and 54 workshops were presented, ranging from basic science to clinical trials and modern treatment of allergic diseases. Here, we summarize the highlights of cellular and molecular mechanisms of allergic disease.

Treatment with chitin microparticles is protective against lung histopathology in a murine asthma model.

BACKGROUND: Chitin, a natural polysaccharide extracted from shrimp, is a potent T and B cell adjuvant when delivered in the form of chitin microparticles and can shift a polarized T-helper type 2 (Th2) immune response towards a Th1 response. OBJECTIVE: We investigated the beneficial effects of the intranasal application of chitin microparticles in newborn mice before and after the establishment of a model of allergic asthma. METHODS: Mice were grouped as asthma (A), primary prevention (PP), treatment (T), primary prevention+treatment (PPT) and control (C) groups. All mice except controls were sensitized with ovalbumin intraperitoneally and challenged intratracheally to establish the asthma model. Mice in the PP and PPT groups received chitin microparticles intranasally during the newborn period before sensitization. Mice in the PPT and T groups received intranasal chitin microparticles after challenge. Airway histopathology was evaluated in all groups. RESULTS: All of the airway histopathologic parameters of small and medium-sized airways of the T and PPT groups were significantly ameliorated when compared with the asthma model group. In the large airways, thicknesses of basement membrane, epithelium and subepithelial smooth muscle layers of the PPT group and basement membrane thicknesses of the T group were also significantly lower compared with the asthma model group. Comparison of the PP group with the asthma model group revealed significantly reduced goblet cell numbers and significantly reduced epithelial and basement membrane thicknesses in small and medium airways, in addition to significantly reduced basement membrane thicknesses in the medium-sized airways. CONCLUSION: Intranasal application of microgram quantities of chitin microparticles had a beneficial effect in preventing and treating histopathologic changes in the airways of asthmatic mice.

Immunological mechanisms of sublingual immunotherapy.

Administration of allergen-specific immunotherapy by the oral route, sublingual immunotherapy (SLIT), has been shown to be effective, with an improved safety profile compared with subcutaneous administration. However, the precise mechanisms underlying the induction of immune tolerance by SLIT remain unclear. Contact of the allergen with the antigen-presenting cells in oral mucosa is likely to be critical. Mucosal Langerhans cells can capture the allergen and transport it to local lymph nodes, which may favour the induction of T lymphocytes that suppress the allergic response. In addition, the production of blocking IgG4 antibodies and the involvement of mucosal B cells appear to play a role. There is a growing evidence to support the role of regulatory T cells in controlling the development of asthma and allergic disease. Nevertheless, there remains a lack of firm evidence that SLIT induces regulatory T cells, although preliminary in vitro data suggest that SLIT may increase interleukin-10, which has a clear role in suppressing the allergic immune response. Further studies are required to determine the involvement of regulatory T cells, the role of different dendritic cell subsets, mucosal B cells as well as the potential use of adjuvants during SLIT.

The effect of BCG vaccine at birth on the development of atopy or allergic disease in young children.

BACKGROUND: Exposure to infectious diseases may reduce the development of asthma or allergy. In particular, the role of the BCG vaccine in modulating asthma or allergy has been a source of speculation. OBJECTIVE: To study newborns from 3 international sites to evaluate the prospective effect of BCG vaccine on allergic diseases or atopic development. METHODS: Infants were enrolled from newborn and well-infant clinics in Thailand, Argentina, and Turkey. The standard BCG vaccine for each country was given at birth. Parents who consented to have their infant included in the protocol completed an allergy family questionnaire. Infants underwent a standard purified protein derivative (PPD) test at 9 to 12 months of age, and the reaction size was measured. At the age of 2 years, the children returned to be studied. Allergy skin tests to common allergens appropriate to location and age were performed, and the parents completed the International Study of Allergy and Asthma in Childhood questionnaire. The PPD reaction size was compared with the presence of atopy and allergy questionnaire responses. RESULTS: A total of 1,704 infants were studied. Statistical significance was found between a negative PPD response vs any positive PPD response and the risk of having an allergic history at the age of 2 years in Turkey (relative risk, 2.11; 95% confidence interval, 1.25-3.55; P = .005) and Thailand (relative risk, 2.16; 95% confidence interval, 1.18-3.94; P = .02) but not Argentina (relative risk, 1.09; 95% confidence interval, 0.70-1.68; P = .70). CONCLUSIONS: This study further supports the role of infectious agents in modulating asthma and allergy development.

Bacillus Calmette-Guérin-induced interleukin-12 did not additionally improve clinical and immunologic parameters in asthmatic children treated with sublingual immunotherapy.

OBJECTIVE: To evaluate the effect of bacillus Calmette-Guérin (BCG) as an adjuvant to specific sublingual immunotherapy (SLIT) on the cytokine profile of peripheral blood mononuclear cells (PBMCs) and clinical outcome. METHODS: Thirty-two children with asthma and rhinitis allergic to house dust mite (HDM) with negative purified protein derivative (PPD) skin test response were enrolled. After a run-in period of 8 weeks, patients were randomized to receive either SLIT only (n=16) or one dose of BCG immunization before initiation of SLIT (n=16) with a standardized Dermatophagoides pteronyssinus (D. pteronyssinus)+D. farinea 50/50 extract. PPD-negative asthmatics (n=5) allergic to HDM receiving inhaled therapy only were included for comparison of cytokine levels in PBMC cultures. Efficacy was assessed both at the end of run-in and 6 months of treatment periods with criteria including symptom, medication and quality-of-life (QoL) scores, IgE levels, lung function, provocation concentration (PC20), eosinophil count and skin prick tests. IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-gamma levels were determined in antigen specifically and polyclonally stimulated PBMC cultures. RESULTS: Both treatment groups showed significant improvement at the end of 6 months for asthma and rhinitis scores and QoL, number of asthma attacks, amount of beta2-agonists, inhaled and intranasal steroids, blood eosinophil counts and PC20. Interestingly, phytohaemagglutinin (PHA)-stimulated IL-12 and D. pteronyssinus-stimulated IFN-gamma in PBMC were significantly higher in the treatment groups than controls. In addition, IL-12 levels in response to D. pteronyssinus and PHA stimulation were significantly higher in the SLIT+BCG group than the SLIT alone group and controls. CONCLUSION: The present study demonstrates that successful SLIT is parallel to increased IFN-gamma production by PBMC. Although simultaneous BCG vaccination enhanced IL-12 production, it did not additionally improve the clinical outcome.

Impact of Mycobacterium vaccae immunization on lung histopathology in a murine model of chronic asthma.

BACKGROUND: Therapeutic modalities of asthma have not been proved to be successful in reversing the already established chronic changes of airways. OBJECTIVE: We aimed to determine the impact of heat-killed Mycobacterium vaccae immunization, a potent Th1 stimulant, on chronic changes of asthma. METHODS: Newborn BALB/c mice were divided into three groups; mice in M. vaccae group received 107 colony-forming units (CFU)/50 micro L of heat-killed M. vaccae subcutaneously on days 3, 14 and 42 before the development of chronic asthma model, whereas mice in control and chronic asthma groups received saline. Subsequently, mice in M. vaccae and chronic asthma groups were administered 10 micro g/100 micro L of ovalbumin (OVA) on days 43, 45, 47, 49, 51, 53 and 55 intraperitoneally, and 20 micro g/10 micro L of OVA on days 83, 86 and 89 intratracheally. Mice in control group received saline on the same days. RESULTS: Comparison of M. vaccae and chronic asthma groups showed statistically significant differences in goblet cell numbers, thickness of basement membrane and subepithelial smooth muscle of small, medium and large airways and epithelial thickness of medium airways. There was no significant difference between the control and M. vaccae groups except for goblet cell numbers of medium and large airways, and epithelial thickness of medium airways. CONCLUSION: Results of our study suggested that immunization by M. vaccae of newborn mice would prevent some of the chronic changes of airways due to asthma.