Thirty-one adult patients with asthma caused by house-dust mites (HDM) were included in this placebo-controlled, double-blind study to evaluate the efficacy and safety of specific immunotherapy (SIT) with biologically standardized extracts of HDM. The specific diagnosis was confirmed by skin prick tests, specific IgE, and bronchial provocation tests with HDM allergens. The patients were randomized to receive active treatment with extracts of either Dermatophagoides pteronyssinus (Dpt) or D. farinae (Dfa) (Alutard SQ, ALK, Denmark) or placebo injections. Twenty-three patients completed the study. After 1 year of treatment, we found a clinically important and significant reduction in both asthma medicine consumption (inhaled steroids 38% and beta 2-agonists 46%) and symptom score (57%) in the actively treated group, but not the placebo group. These findings were confirmed by a significant decrease in skin and bronchial sensitivity to HDM in the active group. Additionally, there was a significant difference in the patients' scores for effect in favor of the actively treated group. Total IgE and specific IgE to HDM showed no significant changes before and after treatment for either group. Spirometric lung-function measurements showed a significant increase in forced expiratory volume in 1 s (FEV1) from 85% before to 89% of predicted values after treatment for the actively treated group. Peak-flow measurements at home showed no significant changes during the study. It is concluded that allergen SIT is an effective treatment in adult patients suffering from asthma due to HDM.
The prognosis of allergic rhinitis was studied in 154 children aged 3-17 years at diagnosis by means of a detailed questionnaire administered 8-11 years later. The symptoms had completely disappeared in only 15 (10%) patients. The conjunctival symptoms, however, had disappeared or were controlled successfully by topical drug therapy in almost all, and 77 (50%) were managing without medication for allergic rhinitis. Twenty-five (23%) of the 110 children with seasonal allergic rhinitis had a perennial disease at follow-up, in contrast to seven (16%) of 44 with perennial allergic rhinitis originally who had only seasonal symptoms at follow-up. Asthma or wheezing had developed in 29 cases (19%) and was more common (p less than 0.01) among those with perennial allergic rhinitis (15 of 44) than among those with seasonal allergic rhinitis (14 of 110). No significant association was found between age at onset of symptoms, family history of atopic disease or type of treatment for allergic rhinitis and allergic rhinitis still present at follow-up or development of asthma during the observation period.
To evaluate the role of lymphocytes in the pathogenesis of allergic bronchoconstriction, we investigated whether allergic airway responses are adoptively transferred by antigen-primed lymphocytes in Brown Norway (BN) rats. Animals were actively sensitized to ovalbumin (OA) or sham sensitized, and 14 d later mononuclear cells (MNCs) were isolated from intrathoracic lymph nodes, passed through a nylon wool column, and transferred to naive syngeneic rats. Recipients were challenged with aerosolized OA or bovine serum albumin (BSA) (5% wt/vol) and analyzed for changes in lung resistance (RL), airway responsiveness to inhaled methacholine (MCh), and bronchoalveolar lavage (BAL) cells. Recipients of MNCs from sensitized rats responded to OA inhalation and exhibited sustained increases in RL throughout the 8-h observation period, but without usual early airway responses. Recipients of sham-sensitized MNCs or BSA-challenged recipients failed to respond to antigen challenge. At 32 h after OA exposure, airway responsiveness to MCh was increased in four of seven rats that had received sensitized MNCs (p = 0.035). BAL eosinophils increased at 32 h in the recipients of both sensitized and sham-sensitized MNCs. However, eosinophil numbers in BAL were inversely correlated with airway responsiveness in the recipients of sensitized MNCs (r = -0.788, p = 0.036). OA-specific immunoglobulin E (IgE) was undetectable by enzyme-linked immunosorbent assay (ELISA) or passive cutaneous anaphylaxis (PCA) in recipient rats following adoptive transfer. In conclusion, allergic late airway responses (LAR) and cholinergic airway hyperresponsiveness, but not antigen-specific IgE and early responses, were adoptively transferred by antigen-primed lymphocytes in BN rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Increasing evidence suggests that alveolar macrophages (AM) are involved in asthma pathogenesis. To better understand the role that these cells play, we investigated the capacity of AM from allergy-resistant rat, Sprague Dawley (SD), to modulate airway hyperresponsiveness of allergy-susceptible rat, Brown Norway (BN). AM of ovalbumin (OVA)-sensitized BN rats were eliminated by intratracheal instillation of liposomes containing clodronate. AM from OVA-sensitized SD rats were transferred into AM-depleted BN rats 24 h before allergen challenge. Airway responsiveness to methacholine was measured the following day. Instillation of liposomes containing clodronate in BN rats eliminated 85% AM after 3 d compared with saline liposomes. Methacholine concentration needed to increase lung resistance by 200% (EC200RL) was significantly lower in OVA-challenged BN rats (27.9 +/- 2.8 mg/ml) compared with SD rats (63.9 +/- 8.6 mg/ml). However, when AM from SD rats were transferred into AM-depleted BN rats, airway responsiveness (64.0 +/- 11.3 mg/ml) was reduced to the level of naïve rats (54.4 +/- 3.7 mg/ml) in a dose-dependent manner. Interestingly, transfer of AM from BN rats into SD rats did not modulate airway responsiveness. To our knowledge, this is the first direct evidence showing that AM may protect against the development of airway hyperresponsiveness.
Comment In: Am J Respir Cell Mol Biol. 2004 Jul;31(1):1-215208095
Comment In: Am J Respir Cell Mol Biol. 2004 Jul;31(1):3-715208096
T lymphocytes may play a regulatory role in the development of allergic airway hyperresponsiveness (AHR). We have studied the relationship between airway responsiveness and a number of immunological changes in Brown-Norway rats sensitized intraperitoneally and repeatedly exposed to ovalbumin (OVA) aerosol. Acetylcholine provocation concentration (PC)150 (the concentration of acetylcholine causing a 150% increase of base-line lung resistance) was measured and peripheral blood and bronchoalveolar lavage (BAL) cells were collected 18-24hr after the final exposure. Total and OVA-specific IgE in serum was measured by enzyme-linked immunosorbent assay (ELISA). Mononuclear cells were analysed by flow cytometry after labelling with monoclonal antibodies against CD2 (pan T-cell marker), CD4, CD8 (T-cell subsets) or CD25 (interleukin-2 receptor). There were significant differences in PC150 (P
There is little information of lower respiratory symptoms, bronchial hyperresponsiveness and airway inflammation in elite ice hockey players. A total of 88 highly trained ice hockey players and 47 control subjects were studied. All the subjects were subjected to skin-prick tests, resting spirometry examinations and histamine-challenge tests. Adequate induced sputum samples were obtained from 68 of the ice hockey players and from 18 symptom-free control subjects on a separate day. Bronchial hyperresponsiveness in a histamine-challenge test was found in 21 (24%) of the athletes and in five (11%) of the controls. Current asthma (current asthmatic symptoms and increased bronchial responsiveness) was observed in 13 (15%) of the athletes and in one (2%) of the control subjects. Total asthma (current asthma or previously physician-diagnosed asthma) occurred in 19 (22%) of the athletes and in two (4%) of the controls. Atopy, according to skin-prick tests, was observed in 51 (58%) of the athletes and 17 (36%) of the control subjects. The differential cell counts of eosinophils (2.6 versus 0.2%) and neutrophils (80.9 versus 29.9%) in the sputum samples of the ice hockey players were significantly higher than in those of the control subjects. Asthma is common in elite ice hockey players and they show signs of a mixed type of neutrophilic and eosinophilic airway inflammation. Inhalation of cold air associated with exposure to indoor pollutants during intensive training is a possible causative factor.
Airway inflammatory responses to specific inhalation challenges (SICs) with low-molecular-weight (LMW) and high-molecular-weight (HMW) agents have not been studied thoroughly. We assessed the changes in airway inflammatory cells following SIC in sensitized workers, and looked at the influence of various factors on the pattern of inflammatory responses to SIC.
Induced sputum analysis was performed in workers sensitized to LMW (n = 41) or HMW agents (n = 41) after a control day and after a positive SIC. Cell counts were compared with lung function and various clinical parameters.
In the LMW group, eosinophils were increased following late asthmatic responses (median [interquartile range], 0.02 [0.04] × 10(6) cells/g vs 0.30 [0.80] × 10(6) cells/g and 1.0% [3.5] vs 8.9% [8.0], P
Trimellitic anhydride (TMA) is a cause of asthma in man. Dose-dependent TMA-specific IgE, histopathology, and airway responses after sensitization by inhalation were examined in the Brown Norway rat. Rats were exposed to 0.04, 0.4, 4, or 40 mg/m3 TMA aerosol for 10 min, once a week, over 10 weeks. All lower exposures were, subsequently, rechallenged to 40 mg/m3 TMA aerosol. All rats received a sham exposure 1 week prior to the first TMA exposure. Following the sham exposure and weekly after each TMA exposure, TMA-specific IgE and both early-phase airway response (EAR) and late-phase airway response (LAR) were measured using enhanced pause (Penh). All rats sensitized by 40 mg/m3 TMA developed specific IgE, EAR, and LAR to one or more of the challenges to 40 mg/m3 TMA. TMA of 4 mg/m3 induced a much lower, but stable, specific IgE response. EAR and LAR were observed only after a 40 mg/m3 TMA rechallenge in this group, but it was much larger than that observed in the 40 mg/m3 TMA-sensitized and challenged group. Exposure-dependent histopathological changes noted included eosinophilic granulomatous interstitial pneumonia, perivascular eosinophil infiltrates, bronchial-associated lymphoid tissue hyperplasia, and peribronchiolar plasma cell infiltrates.
A study was undertaken in a number of rowhouses, some of which had had previous problems related to dampness and water leakage. The aim of the study was to assess the relation between exposure to airborne (1--> 3)-beta-D-glucan, a cell-wall substance in molds, and airways inflammation. The study involved 75 houses with indoor (1--> 3)-beta-D-glucan levels ranging from 0 to 19 ng/m3. Of 170 invited tenants, 129 (76%) participated in the study. A questionnaire relating to symptoms was used, and measurements were made of lung function and airway responsiveness. Myeloperoxidase (MPO), eosinophilic cationic protein (ECP), and C-reactive protein (CRP) were measured in serum. Atopy was determined with the Phadiatop test. The major findings were a relation between exposure to (1--> 3)- beta-D-glucan and an increased prevalence of atopy, a slightly increased amount of MPO, and a decrease in FEV1 over the number of years lived in the house. The results suggests the hypothesis that exposure to (1--> 3)-beta-D-glucan or molds indoors could be associated with signs of a non-specific inflammation.
The absence of IgE sensitization to allergen components in the presence of sensitization to the corresponding extract has been reported, but its clinical importance has not been studied.
To evaluate the clinical significance of IgE sensitization to three aeroallergen extracts and the corresponding components in relation to the development of respiratory disease.
A total of 467 adults participated in the European Community Respiratory Health Survey (ECRHS) II and 302 in ECRHS III, 12 years later. IgE sensitization to allergen extract and components, exhaled nitric oxide (FeNO) and bronchial responsiveness to methacholine were measured in ECRHS II. Rhinitis and asthma symptoms were questionnaire-assessed in both ECRHS II and III.
A good overall correlation was found between IgE sensitization to extract and components for cat (r = 0.83), timothy (r = 0.96) and birch (r = 0.95). However, a substantial proportion of subjects tested IgE positive for cat and timothy allergen extracts but negative for the corresponding components (48% and 21%, respectively). Subjects sensitized to both cat extract and components had higher FeNO (P = 0.008) and more bronchial responsiveness (P = 0.002) than subjects sensitized only to the extract. Further, subjects sensitized to cat components were more likely to develop asthma (P = 0.005) and rhinitis (P = 0.007) than subjects sensitized only to cat extract.
Measurement of IgE sensitization to cat allergen components would seem to have a higher clinical value than extract-based measurement, as it related better to airway inflammation and responsiveness and had a higher prognostic value for the development of asthma and rhinitis over a 12-year period.