The size of the disease relevant IgE antibody fraction in relation to 'total-IgE' predicts the efficacy of anti-IgE (Xolair) treatment.

BACKGROUND: Some patients with allergic asthma treated with anti-IgE (Xolair) do not become symptom free. Better criteria for response assessment than allergy skin tests or IgE determination are needed. The impact of the size of the disease relevant allergen-specific IgE antibody fraction, i.e. the percentage of IgE antibody of total IgE, was evaluated in cat allergic patients treated with the recommended doses of Xolair. Results were measured as changes in basophil allergen threshold sensitivity (CD-sens). METHODS: In a double-blind placebo controlled trial 20 patients with a high (>3.8%) and 18 with a low (<1%) percentage of IgE antibodies to cat were given Xolair for 16 weeks and the change in CD-sens was compared to 11 and 10 patients, respectively, in each group receiving placebo. RESULTS: The CD-sens dropped significantly in both the high (P < 0.001) and low (P < 0.001) group on Xolair but did not change significantly after placebo. For Xolair-treated patients, at the end of the trial there was a highly significant (P < 0.001) difference in CD-sens between the high group, where no patients, and the low group, where 13/18 patients, had become negative. CONCLUSIONS: The currently recommended doses of Xolair very efficiently eliminate IgE antibodies if the IgE antibody fraction is <1% of total IgE but has not enough effect on allergen sensitivity if the fraction is >3-4%. Further studies will show if increased doses of Xolair would help also these patients, who seem to represent about 1/3 of the patient population.

Nasal histamine reactivity among adolescents in a remediated moisture-damaged school--a longitudinal study.

UNLABELLED: In a previous study, in the spring of 1995, we found that teachers, who had been working for several years in a moister-damaged school, 1 year after the renovation still reported a higher frequency of complaints and symptoms and showed significantly higher mucosal histamine reactivity compared with teachers in a control school, although the school seemed to be properly renovated. A longitudinal study of 90 randomly selected senior high school students entering the two schools was initiated to exclude or verify if the indoor air still exerted an irritant effect on the upper airways of an earlier unexposed group. The students went through a nasal histamine provocation test and answered a questionnaire on three occasions, in 1995, 1996 and 1997. No significant differences in the nasal histamine provocation curves for the students at the target school and those at the control school could be shown from start to endpoint of the study period. Neither was there any differences concerning perceived indoor air or mucosal symptoms between the target and the control group and technical measurements showed no noteworthy differences between the two schools. In conclusion, this study indicates that based on both technical and objective medical measures, the current indoor air in the remediated moisture-damaged school does not exert an irritant effect on the upper airway mucosa of the students. A 2-year follow-up of the teachers showed a decreased reactivity to histamine, giving further support to this statement. The increased mucosal reactivity observed among the teachers is probably a result of the previous long-term exposure to building dampness. No differences were seen between atopic and non-atopic students. PRACTICAL IMPLICATIONS: Persistent symptoms and increased nasal mucosal reactivity among personnel in a remediated damp building does not necessary imply an inadequate renovation. A longitudinal study with registration of subjective (questionnaires) and objective (nasal histamine reactivity) data of an earlier unexposed group residing in the same building further contributes to the evaluation whether the renovation was successful or not.

Nasal mucosal histamine reactivity among young students and teachers, having no or prolonged exposure to a deteriorated indoor climate.

BACKGROUND: In a study performed in the spring of 1995, we found a significantly greater nasal mucosal histamine reactivity among teachers, who had worked for several years in a recently renovated moisture-damaged school, than in those in a control school. In the present study we investigated the students who begun their high-school studies at both schools in the autumn of 1995 and compared them with the teachers as regards mucosal reactivity, atopy and symptoms. METHODS: Twenty-eight teachers in the target school, 18 teachers in the control school and 45 students from each school underwent a nasal histamine provocation test and a skin-prick test. They also answered a standardized questionnaire. RESULTS: The teachers in both schools had more marked nasal mucosal histamine reactivity at the lowest provocation concentrations than the students. The histamine provocation curve of the target school teachers had consistently higher values than that of the students (P = 0.0001), but its slope and shape were similar (P = 0.15), while the slope of the provocation curve of the control school teachers was flatter. However, there was only a borderline significance in this respect compared to the students (P = 0.07). Teachers with a dry and crusty appearance of the nasal mucosa on anterior rhinoscopy reacted more strongly to histamine provocation than those without this finding (P = 0.0004). There was a significantly higher frequency of skin-prick test positivity (SPT+) among the students (P = 0.03). There were no significant differences in nasal mucosal histamine reactivity between atopic and non-atopic subjects out of pollen season. CONCLUSIONS: Teachers had a significantly greater mucosal histamine reactivity than the students, whereas the latter had a significantly higher frequency of atopy. These results are compatible with an age-related pattern of mucosal reactivity. A crusty appearance of the nasal mucosa seems to predispose to an increase in histamine reactivity. There were no significant differences according to histamine reactivity between atopic and non-atopic subjects.

Slowly decreasing mucosal hyperreactivity years after working in a school with moisture problems.

In our first study in 1995, teachers, who had worked in a water-damaged school for more than 5 years, were tested for nasal histamine reactivity by rhinostereometry. They were found to have significantly increased reactivity compared with teachers in a school without these indoor-climate problems. This finding could not be explained by differences in atopy or other personal characteristics. In this 2-year follow-up study (1995-97), 26 of 28 teachers in the target school and all 18 teachers in the control school, who participated in the initial study, accepted to take part. They were tested with the same histamine provocation procedure and answered the same questionnaire as 2 years earlier. Technical measurements of temperature, relative humidity, dust, carbon dioxide, formaldehyde and total volatile organic compounds (TVOC) were carried out in both schools during the time period between the two test occasions. In this provocation test, the teachers from the repaired water-damaged school still demonstrated an increased reactivity to histamine compared with the teachers in the control school, but the difference between the growth curves of the provocation tests was less than in 1995. Teachers in the target school still complained about the indoor air quality more than their colleagues, although the complaints were less common. No major differences were observed in the technical investigation between the two schools and the measurements were all within values usually seen in schools in northern countries. Our conclusion is that the observed nasal mucosal hyperreactivity among the teachers in the renovated water-damaged school seems to persist over years and only slowly decrease even after successful remedial measures have been taken.

Nasal hyperreactivity among teachers in a school with a long history of moisture problems.

Upper airway symptoms have frequently been reported in people working or residing in damp buildings. However, little information has been available on objective pathophysiologic findings in relation to these environments. Twenty-eight teachers, who had worked for at least five years in a recently renovated school that had had severe moisture problems for years, were randomly selected for this study. Eighteen teachers, who had worked in another school that had no moisture problems, were randomly selected to serve as the control group. Although remedial measures had been taken, an increase in the prevalence of mucous membrane irritations was still reported by the teachers in the target school. We used a nasal challenge test with three concentrations of histamine (1, 2 and 4 mg/mL). Recordings of swelling of the nasal mucosa were made with rhinostereometry, a very accurate optical non-invasive method. The growth curves of mucosal swelling induced by the three concentrations of histamine differed significantly between the two groups (p < 0.01). The frequencies of atopy, evaluated with the skin-prick test, were almost identical in both groups. The study indicates that long-term exposure to indoor environments with moisture problems may contribute to mucosal hyperreactivity, of the upper airways. Such hyperreactivity also seems to persist for at least one year after remedial measures have been taken.

Activated T cells in the nasal mucosa of patients with grass-pollen allergy. A pilot study.

Six patients with grass-pollen allergy were provoked with water-soluble grass pollen until a pronounced allergic reaction occurred. This was performed outside the grass-pollen season, and the allergen was administered on the edge of the inferior turbinate. Biopsies were taken both before provocation and during the reaction, 15-30 minutes after provocation. The nasal population of immunohistochemically positive cells for HLA-DR, CD1, interleukin-2-receptor, IgE, CD4 and CD8 were studied. There was a marked increase of IL2-R-positive cells (activated T lymphocytes) in the nasal mucosa after provocation, whilst the other cell populations approximately remained unchanged (apart from a certain increase of IgE). The increase of activated T lymphocytes may imply that certain subsets of T cells play a role in the allergic response, and that the role of helper T cells very likely is much more complex than the regulation of mast cells and eosinophils. The concomitant presence of Langerhans' cells (CD1-positive) and activated T lymphocytes may indicate a possible association on site between an antigen-presenting cell and both effector as well as memory cells in allergic reactions.

Treatment of sinus empyema in adults. A coordinated Nordic multicenter trial of cefixime vs. cefaclor.

In sinus empyema, H. influenzae is the most prevalent pathogen in some subpopulations and in case of therapeutic failure. Cefixime, the first oral cephalosporin of the 3rd generation, is highly potent in vitro against H. influenzae. To study the efficacy and safety of cefixime in adults with acute sinusitis, a coordinated, double-blind multicenter trial was designed for purulent cases, as confirmed by antral aspiration. A total of 364 patients were enrolled in the study with 125 cases randomized to the reference group, assigned to treatment with cefaclor. Evaluation was based on clinical outcome and on antral reaspiration (86% of the cases). No significant differences between the treatment groups were found, as regards short-term or long-term clinical outcome. However, the clinical examination overestimated the therapeutic results. Only 4% of the patients were considered as failures, but the re-aspiration demonstrated remaining suppuration in 14% of all cases (p less than 0.001). Based on re-aspiration, the failure rate among patients with initial growth of pathogens was lower for cefixime (8%) than for cefaclor (20%) (p less than 0.05). Such a difference was not found among patients with growth of H. influenzae. No serious adverse reactions were recorded, but loose stools and diarrhoea were significantly more frequent in the cefixime treatment group. Five patients (2%) in the cefixime treatment group discontinued their treatment due to adverse events.